P News
randall
http://www.eurekalert.org/pub_releases/2006-03/uomh-usi031506.php
Contact: Sally Pobojewski
University of Michigan Health System
U-M scientists identify major psoriasis susceptibility gene
Found with genes that control human immune response, discovery could
lead to safer and more effective psoriasis treatments
University of Michigan scientists have found a common genetic variation
in an immune system gene that makes people much more likely to develop
psoriasis - a disfiguring inflammatory skin disease.
Named PSORS1 (SORE-ESS-1), for psoriasis susceptibility 1, the gene is
the first genetic determinant of psoriasis to be definitively
identified in a large clinical study. Its discovery could lead to new,
more effective treatments for psoriasis without the risks and
side-effects of current therapies.
The gene's causative role in psoriasis was demonstrated in a University
of Michigan Medical School study of 2,723 people from 678 families in
which at least one family member had the disease.
Results of the U-M study - the most comprehensive analysis of a
psoriasis gene to date - will be published in the May 2006 issue of
the American Journal of Human Genetics.
Psoriasis is a chronic disease that affects about 2 percent of the U.S.
population. People with psoriasis develop thick, flaky white patches on
their skin and scalp. The disease is disfiguring and can have a
negative effect on quality of life. About 25 percent of people with
psoriasis eventually develop psoriatic arthritis, which can be severe.
Unlike diseases caused by a mutation in just one gene, psoriasis is
what scientists call a multi-factorial disease. This means that people
must inherit several disease-related genes, plus be exposed to one or
more environmental triggers, in order to get psoriasis.
"For every individual with psoriasis who carries the PSORS1 gene, there
are 10 other people with the gene who don't get psoriasis," says study
director James T. Elder, M.D., Ph.D., a professor of dermatology and of
radiation oncology in the U-M Medical School and the Ann Arbor VA
Healthcare System.
"It's as if you are pushing a shopping cart down the aisle at the
grocery store and putting genes in your cart," Elder adds. "There are
several different brands of each gene on the shelf and one of them is
bad for you. If you pull down enough bad ones, then you can get sick.
"But even if you get all the bad genes, you still need a trigger from
the environment to develop the disease," explains Elder. "In psoriasis,
strep throat is a very common initial trigger. It activates the immune
system to attack the strep bacteria. But once the strep infection is
cleared, the immune system starts attacking the patient's own skin
cells.
About half the time, strep-induced psoriasis goes away and never comes
back. But for the other 50 percent of young people who get it,
psoriasis progresses to become a chronic life-long disease."
The PSORS1 gene is actually one of over 20 different varieties
(scientists call them alleles) of a gene called HLA-C. "In terms of our
grocery store analogy, think of PSORS1 as one of 20 'brands' of HLA-C
on the shelf," Elder says.
Located on human chromosome 6, HLA-C is one of several genes in the
major histocompatibility complex (MHC) that regulate how the immune
system fights off infection. MHC genes carry DNA-coded instructions for
proteins whose job it is to distinguish between what belongs in the
body and what doesn't.
"There is a great deal of genetic variation in the MHC, because it's on
the front lines of dealing with pathogens and cancer," Elder explains.
"It's an area where it's good to be different. If everybody were the
same, we'd be like hybrid corn. A plague could come along and wipe us
all out."
Scientists have been searching for genes associated with psoriasis for
more than 30 years, but until now studies have been inconclusive,
according to Rajan P. Nair, Ph.D., the study's first author and a U-M
assistant research professor in dermatology.
"Researchers have identified 19 candidate loci, or areas on
chromosomes, that may be genetically linked to psoriasis," Nair says.
"Many studies confirmed a strong association with the MHC, but no one
could determine which gene in the MHC was involved in psoriasis."
In a previous study, Nair and his U-M colleagues narrowed the search
for the PSORS1 gene down to a 300,000-base-pair segment of chromosome 6
that included HLA-C and at least 10 other genes.
To determine which of the 11 genes was linked to psoriasis, U-M
scientists used a technique called haplotype mapping. Haplotypes are
clusters of alleles that tend to be inherited together as a group,
because they are located close to each other on the same chromosome.
This means that small individual variations in DNA, which originated in
a distant ancestor, are often passed intact from generation to
generation. If a haplotype contains genetic changes that make people
more susceptible to a disease, scientists can find it by comparing DNA
sequences in haplotypes from people with the disease to those of people
who don't have the disease.
U-M researchers first sequenced and compared all DNA within the 300,000
base-pair target segment from 10 MHC chromosomes carried by five people
enrolled in the study. Detailed analysis of these 10 DNA sequences
revealed differences that were only present on psoriasis chromosomes,
but never on normal chromosomes. Further analysis by U-M scientists
narrowed the search down to one gene, HLA-C, and one specific
disease-causing allele, HLA-Cw6.
Drugs used to treat psoriasis are also used for other autoimmune
diseases, such as lupus and rheumatoid arthritis. These drugs turn off
the immune response, which leaves the body vulnerable to infection. Now
that U-M scientists have identified HLA-Cw6 as being the PSORS1 gene,
Elder says scientists can concentrate on finding ways to block its
ability to bind to cell surface antigens, which could lead to the
development of safer treatments for psoriasis.
"What we're all shooting for is trying to find out which branches of
the immune system are triggering psoriasis, so you don't have to shut
down the whole immune system - only the parts that are important,"
Elder says.
While Elder believes that PSORS1 is the major gene involved in
susceptibility to psoriasis, he cautions that it's not the only one. He
says much additional research will be required to find the other genes
involved and to understand all the secrets of this complex and puzzling
disease.
"Access to a large, diverse pool of study subjects is vital to the
success of this type of clinical research," Elder says. "We are
grateful to the 5,000 people who have participated in our psoriasis
study so far. It has been a collaborative effort involving physicians,
scientists and patients from dermatology departments at many
institutions - including the U-M, the University of Kiel in Germany,
Detroit's Henry Ford Hospital, and the Ann Arbor VA Healthcare System."
###
Editors: A color image showing typical lesions seen in patients with
psoriasis is available on request.
The study was funded by the National Institute of Arthritis,
Musculoskeletal, and Skin Diseases, the Dudley and Dawn Holmes Fund,
the National Psoriasis Foundation, and the National Center for Research
Resources.
Additional U-M collaborators in the study include Philip E. Stuart,
senior research associate; research fellows Ioana Nistor, M.D., Ravi
Hiremagalore, M.D., and Nicholas Chia, M.D.; Goncalo R. Abecasis, D.
Phil., associate professor of biostatistics and John J. Voorhees, M.D.,
the Duncan O. and Ella M. Poth Distinguished Professor of Dermatology.
Citation: American Journal of Human Genetics, May 2006 (in press).
NOTE: The paper is posted on the journal's preprint Web site at
www.journals.uchicago.edu/AJHG/journal/preprints.epl. The site is
available to journal subscribers only. If you do not have a
subscription, contact Sally Pobojewski to receive a copy of the paper.
------------------------------------------------------------------------------------------------
another note::: Send some $ to the NPF by joining up. They need our
support.
Abstract du jour::
Biologicals dramatic advances in the treatment of psoriasis.
Wilsmann-Theis D, Martin S, Reber M, Kwiek B, Bieber T, Novak N.
Department of Dermatology, University of Bonn, Sigmund-Freud-Strasse
25, 53105 Bonn, Germany. Natalij...@ukb.uni-bonn.de.
Innovations in biotechnology have made possible the development of
several new systemic therapies for psoriasis - the "biologicals", a new
group of compounds including monoclonal antibodies, fusion proteins and
recombinant proteins. These novel biotechnological advances potentially
offer designer drugs, which interfere with specific targets in the
pathophysiological network of psoriasis and are thus much safer. The
therapeutic strategy of biologicals is based on the knowledge derived
from pathogenetic studies, which have focused on targeting disease
relevant T-cell- or mediator-systems. Important targets include
inactivation of soluble mediators such as tumor-necrosis-factor-alpha,
the blockade of receptors for cytokines, adhesion molecules and the
interference with T-cell activation by antigen-presenting cells. In
addition, recombinant cytokines are able to modulate the immunological
balance of this chronic inflammatory skin disease. Currently, up to
forty agents are under investigation for the treatment of psoriasis.
Four of these agents, alefacept, efalizumab, etanercept and infliximab
have already impacted on routine clinical practice. Current
developments in the treatment of psoriasis with biologicals are
reviewed.
PMID: 16533166
randall....
randall
P News from around the World.
Bed ridden psoriatic cured by yoga breathing in India,
http://cities.expressindia.com/fullstory.php?newsid=174401
THE REAL HOT BABE
THIS CARDIAC SURGEON SPENDS MOST OF HER TIME CONDUCTING YOGA WORKSHOPS
FOR PHYSICAL AND MENTAL WELL-BEING
Healing from within
Zeenat Nazir
SHE coaxes her students to stretch those tense, stiff muscles, relax
their stressed minds and discover the peace within. Meet Dr Renu
Mahtani, whose unusual and innovative yoga techniques have enabled many
overcome their physical and mental ailments and infused in them a fresh
lease of life.
Mahtani, a practising physician and cardiac surgeon, has been
conducting wellness workshops in the city for the past two years. A
student of Banaras, Hindu University, Mahtani reveals, "Having moved
to Pune 16 years ago, I started working at Ruby Hall Clinic and later
started my own practise. Everything about my life was perfect."
But, as fate would have it, Mahtani developed psoriasis-an incurable
skin disease-in 1996. As the illness progressed, this once energetic
and vivacious lady was confined to the bed. "I was in a painfully
crippled condition and was unable to venture outside my home for two
years. But I was not ready to accept this as my destiny. I tried out
all kinds of medicines, but nothing gave me the desired results.
That's when I decided to develop a positive mindset and surrender
myself completely to the will of God," recalls the spirited lady.
Luckily, Mahtani chanced upon a renowned pranayam expert from Mumbai,
six years ago. Informs the doctor, "That was when I began to pick up
this age-old genuine science, the breathing techniques of which have
cured the incurable." Interestingly, Mahtani feels that pranayam is
much more than mere breathing - it is a tool to enrich the mind.
"90 per cent of all illnesses occur when the mind is agitated, which
in turn leads to anxious breathing. So we work in reverse. Through
controlled, conscious breathing, we can relax the mind and keep illness
at bay," she says.
Mahtani's endeavours finally bore fruit in 2001, when she was
completely cured of her disease through daily yoga sessions. Wanting to
share the advantages of pranayam with others, she decided to conduct
workshops for some of her patients as well. "The class has become so
popular, that I now conduct four batches comprising 20 students each,
everyday. Moreover, these classes are specially designed to cater to
problems of women, senior citizens and convalescents," enthuses the
lady, who interestingly, won the first ever Mrs Pune contest in 1997.
Of late, Mahtani has also begun conducting specific workshops for
diabetics, asthmatics and those with heart problems. "Using
techniques published in international journals, I have designed special
pranayam exercises for children with learning disorders and dyslexia.
Through these exercises, children learn to coordinate their breathing
with motor activities, improving concentration and memory."
Mahtani's efforts have also extended to helping students deal with
stress and tackling societal and parental pressures. Quips the expert,
"These days, students are physically inactive and low in tolerance.
Hence, I often impart yoga training for the benefit of University of
Pune students."
For her youth-oriented classes, Mahtani makes sure to imbibe techniques
like the exercise ball and Pilates. Like most experts, she also
stresses the need to include yoga in the school curriculum. This
strong-willed lady also believes in giving back to the community
through her oft-conducted, free-for-all workshops. "Just recently, I
conducted a free workshop for women on the occassion of Women's Day.
I feel blessed to be able to share these natural techniques with the
less fortunate," smiles the expert.
When she isn't reading and absorbing classical music, Mahtani
indulges in her passion-cooking. "Mind you- healthy cooking," she
corrects me. Infact, Mahtani has also written a book titled The
Ultimate Indian Diet Book, which gives quick recipes to deliciously
healthy food.
"Yoga is effective only if it is accompanied by spirituality. It is
only belief that leads to hope and finally to cure," signs off the
expert.
-----------------------------------------------------------------------------------
Looks as if Dr. Mahtani found the Pagano Indian diet for Psoraisis.
http://www.hinduonnet.com/thehindu/mp/2005/05/02/stories/2005050201470300.htm
Vote for vegetarianism
Renu Mahtani's "The Ultimate Indian Diet Book" points one on the right
direction
For Renu Mahtani, it has been years now that she is eating to live and
not living to eat. An MD in Medicine, Pune-based Renu had suffered from
psoriasis, almost a decade ago. Though herself a doctor, she found no
answer in medicine beyond a limit.
"And so, I took to working on the right diet and believe it or not, it
is been seven years and I am completely cured." Her self-experiment led
her to broaden her "vision about health," and took her beyond
allopathy. And recently, Renu has come out with her maiden book The
Ultimate Indian Diet Book attempting to take the readers through the
science of food vis-à-vis Indian food habits.
Published by Macmillan, the 173-page book is not a usual copy of leaf
after leaf of recipes, (though it has a few recipes to take you towards
the required direction) but filled with her explanations on what is the
right food for you. "When I was suffering from psoriosis, I realised
the limits of allopathic cure. I wanted others too to know the
boundaries of medical knowledge. But when you want to find out about
the right food habits in books, all we find are western publications.
They suggest you to have avocadoes and asparagus, which you don't find
in your local market. Also, Indian appetite and taste are so different
from the West. All these have made me write this book," she explains.
A clear voter for vegetarianism, she quit non-vegetarian food some
years ago and is "reaping" its benefits now. "I am so much calmer,
there is such clarity of thought now. There is a general lightness of
the body that you get to enjoy being a vegetarian," she says.
And in her book too, she has devoted quite a few chapters on
vegetarianism.
"I know that the vegetables and fruits that you get now are generally
not free from chemicals. But you can dip them in water for some time
before eating. Nothing these days is perfect, the art lies in making
things suitable for you," she states.
A regular practitioner of pranayama, Renu is already planning her next
book on the concepts of breathing and meditation.
SANGEETA BAROOAH PISHAROTY
-----------------------------------------------------------------------------------
So.... Can we explain this cure?
Sure!
On a vegetarian diet Dr. Mahtani eventually rebuilt her colon flora to
re-uPregulate IL-10 and unSKEW the Th1 cytokines. She lives a lifestyle
that homeostatically denies the bad flora in the gut the ability to
achieve a
ratio that will skew her immune system back towards an inflammatory
paradigm.
Big Deal if you can live that whey!
randall.... Pushing the *I did it my WHEY* way to live with P!
randall
P tests in the news and another P Diet book today.
The MAb disaster for the six young men in London,
http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=38490
[...]
The Medicines and Healthcare products Regulatory Agency (MHRA) in
London is investigating the hospitalization of six men who took part in
a Phase I trial of TGN1412, an immunomodulatory humanized agonistic
anti-CD28 monoclonal antibody designed to treat chronic inflammatory
conditions and leukemia.
The men were admitted the evening of March 13 to the critical care unit
of Northwick Park Hospital after an undisclosed inflammatory disorder
emerged, affecting some organs. As of late March 15, two remained in
critical condition, while the other four were in serious condition but
showed some signs of improvement.
[...]
"It's incredibly, incredibly rare, if not unprecedented, for this
sort of thing to have happened," she said, emphasizing that the safety
of monoclonal antibody drugs in general should not be in question.
There currently are 17 monoclonal antibody drugs on the market
worldwide, all of which passed thorough clinical safety studies.
Of those approved in the U.S., several were developed by South San
Francisco-based Genentech Inc.: Rituxan, for non-Hodgkin's lymphoma;
Herceptin, for metastatic breast cancer; Xolair, for asthma; and
Raptiva (co-developed with XOMA Ltd.) for psoriasis. The first
monoclonal antibody approved was Orthoclone (Johnson & Johnson) in 1986
for allograft rejection, and one of the most recent approvals, in
February 2004, went to Erbitux, ImClone Systems Inc.'s drug for
colorectal cancer. The New York-based company recently received
approval to expand the drug's use into head and neck cancer.
<snIP>
http://www.pharmaceutical-business-review.com/article_news.asp?guid=98D55E80-9064-4142-813B-D49822A2B90F
Isotechnika reports positive safety data for psoriasis drug
21st March 2006
Isotechnika has obtained encouraging preliminary 48-week clinical
safety data from its phase III psoriasis and extension trials for its
lead immunosuppressive drug, ISA247
Patients completing the 24-week Canadian phase III trial, named SPIRIT,
were given the opportunity to continue therapy for an additional 36
weeks or to discontinue therapy. Those patients who chose to enroll in
the extension trial were moved from the 0.2mg/kg bid (low dose) or
0.4mg/kg bid (high dose) groups into the 0.3mg/kg bid (mid dose) group.
Patients who commenced the SPIRIT trial in the 0.3mg/kg bid dose group
remained on the same dosage regimen for the duration of the extension
trial.
<sniP>
http://feed.insnews.org/v-cgi/feeds.cgi?feedid=150&story_id=1704569
[...]
BLOCKBUSTER TO BE? UCB's most exciting new drug is Cimzia. The
antibody-based medicine is being targeted initially at people with
Crohn's disease, a chronic inflammatory disorder of the digestive tract
that affects nearly 1 million patients worldwide. If the U.S. Food &
Drug Administration approves Cimzia, the drug will likely hit the
market next year. UCB is also testing Cimzia for other inflammatory
conditions, such as rheumatoid arthritis and _____psoriasis______.
Although it will compete against Johnson & Johnson's (JNJ) Remicade,
and Abbott Laboratories' (ABT) soon-to-launch Humira, analysts are
optimistic that Cimzia has blockbuster potential. <sniP>
A new book on beating your P.
http://www.emediawire.com/releases/2006/3/emw361171.htm
Registered Dietitian and Noted Speaker, Deirdre Earls, Teaches How Food
Can Be Your Best Medicine
Experience the miraculous healing power of food with Deirdre Earls'
step-by-step guidebook for busy people, Your Healing Diet.
Austin, TX (PRWEB) March 22, 2006 -- In Deirdre Earls' new book, Your
Healing Diet: A Quick Guide to Reversing Chronic Diseases through
Healing Foods, readers will learn how to take charge of their lives
with a healthy, natural diet system tailor-made for those with
fast-paced lifestyles.
Now it's easier than ever to reap the benefits of the healing power
of food with Deirdre Earls' guidebook, Your Healing Diet. Whether you
suffer from allergies, fatigue, arthritis, autoimmune disease,
________psoriasis_______, or eczema, the right diet can conquer disease
and give you back the health you deserve. In clear, easy to understand
prose, Earls shows you how the wrong diet can wreak havoc with your
body chemistry. She points out the types of food you should eat
instead, detailing why and how those foods can influence natural
healing and prevent a myriad of diseases.
Because Earls understands that busy people often don't have time to
research or shop, she's done all the legwork for you. In Your Healing
Diet, she shows you what to look for at the grocers and how to stock
your refrigerator for optimum health. She explains why you need to chew
more, how to avoid extremes in your diet, and why you should start
preparing your food with loving energy and care. You'll also discover
what foods to avoid, and how the simpler you keep your diet, the better
off you will be. Best of all, Earls includes easy-to-fix healing meals
and snacks that you can prepare and carry anywhere..
Modern medicine treats symptoms of disease; healing the body from the
inside out with food can reverse and prevent many chronic diseases..
With patience, persistence and commitment, you'll be happier and
healthier. Health is wealth, and this handy, informative guide can help
you cash in on all the wonderful benefits.
For more information or for a free review copy, please contact the
author through her website at www.YourHealingDiet.com, or call (512)
453-8784. Your Healing Diet is also available for sale online at
Amazon.com, Borders.com, BookSurge.com, and through additional
wholesale and retail channels worldwide.
About the Author
An honors graduate with a degree in Scientific Nutrition from Texas
A&M, Deirdre Earls, RD, LD, is a virtual poster-woman for the healing
diet. After thirty years of struggle with ________her severe
psoriasis___________, she finally refused the recommended chemotherapy
treatment and began to research and reverse her condition with
nutrition. A featured speaker for Registered Dietitians and
internationally recognized organizations such as Whole Foods Market and
The National Psoriasis Foundation, Ms. Earls has also been published in
Prevention magazine and Austin Fit Magazine. Her nutrition practice
provides personalized dietary guidance that emphasizes natural healing
with food for those with busy lifestyles.
About BookSurge
BookSurge LLC, an Amazon.com company, is a global leader in
self-publishing and print-on-demand services. Offering unique
publishing opportunities and access for authors, BookSurge boasts an
unprecedented number of authors whose work is picked up by traditional
publishers and successful authorpreneurs who use their valuable
expertise to enhance or build a business with their book.
###
I wonder if this book reads like pagano or that vegetarian yoga book
from Dr. Renu Mahtani the other day?
If you missed it,
http://cities.expressindia.com/fullstory.php?newsid=174401
randall.... diet or drugs? No one wants to die from a bad MAb!
randall
That does it. After reading cruiser's latest post, i'm ready to stand
on my
head and breathe deePly. Forget the vegetarian yoga diet. We only
need O2 in those little grey cells. ;-)
Oh and welcome back from your ski 'n triP cruiser! I hope it wasn't on
your mind at all.... as if. lol
Today's regular old p news from around the world.
Does this cream smell fishy or is it all on my skin?
http://www.news-medical.net/?id=16874
[...]
A new skin cream has shown promising results in the treatment of
psoriasis and eczema. The cream contains fish enzymes and gelatine and
is under development by researchers at the Norwegian University of
Science and Technology (NTNU) in Trondheim and the University of
Bergen, Norway.
An important ingredient in the product is the enzyme zonase, which is
found in fish eggs. The enzyme can break down dead skin cells without
harming living cells. Used in the treatment of psoriasis, this cream
helps to dead skin to flake off, while stimulating the growth of new
cells.
But enzymes need water to function as they should. With typical creams,
the moisture evapourates a short time after application to the skin.
The challenge for manufacturers is to find a new and better method to
bind water to the cream. Dr. Ingvild Haug is a specialist in fish
collagen (gelatine)
[...]
All day, workers had their hands in the cold sea water, handling the
salmon fry. Usually, such activities would lead to red and chapped
skin. But those who worked with the salmon fry had surprisingly soft
and supple skin. The Bergen researchers looked into the case and found
the enzyme zonase to be the reason.
----------------------------------------------
This story above reminds me of that gunk stuff on a new born baby.
Didn't
they come up with something for that stuff as well? IIRC they did?
LL-37 and Vaccinia back in the news
http://www.news-medical.net/?id=16844
Immune system protein LL-37 critical in controlling replication of
vaccinia virus
Medical Research News
Published: Thursday, 23-Mar-2006
[....]
Comparing immune responses of skin cells grown in the lab from healthy
volunteers and from people with atopic dermatitis, the researchers
found that the latter skin samples produced excessive amounts of IL-4
and IL-13. Adding IL-4 and IL-13 to skin cells from healthy volunteers
prior to vaccinia exposure reduced levels of LL-37 production.
Conversely, when the scientists applied IL-4- and IL-13-neutralizing
antibodies to skin samples from people with atopic dermatitis, LL-37
production increased significantly.
Together, these findings suggest a rationale for new treatment
approaches to eczema vaccinatum, notes Dr. Leung. One approach involves
developing drugs to mimic the action of LL-37 or developing
LL-37-containing creams that could be applied to the skin in order to
boost its ability to contain vaccinia virus infection. Another approach
could be to develop agents to neutralize IL-4 and IL-13. Although no
such drugs are currently marketed, compounds that can neutralize IL-4
and IL-13 are under study as possible asthma and allergy treatments,
Dr. Leung says, and might also be applied to eczema vaccinatum
treatment.
Smallpox vaccine, which is made with live vaccinia virus (a close
relative of the virus that causes smallpox), has not been routinely
given in the United States since the early 1970s. But recent concerns
about the possibility of a bioterrorist attack using smallpox virus
prompted authorities to reinstate voluntary smallpox vaccination for
specific groups, such as military personnel. In the first five months
of 2003, the U.S. Department of Defense vaccinated more than 450,000
personnel against smallpox. During this period, the majority of those
who deferred vaccination cited atopic dermatitis or other skin
conditions as the main reason.
While P is Th1 with it's own nasty cytokine profile, it's always nice
to
know the fliP side of the coin. Atopic dermatiits is Th2 and has IL-4
and IL-14
among others to contend with,
http://groups.google.com/groups/search?q=ll-37+psoriasis&qt_s=Search
Yet knowing these pathways may be invaluable in a biological warfare
scenario.
Think back just last week. One little superMAb con blow uP your mind.
Literally!
--------------------------------------------------------------------------------------------------------
Genes and things (comparing P and cancer skin)
Expression of genes involved in the regulation of p16 in psoriatic
involved skin.
Mark EB, Jonsson M, Asp J, Wennberg AM, Molne L, Lindahl A.
Department of Dermatology, Sahlgrenska University Hospital, Goteborg
University, 413 45, Goteborg, Sweden, elisabeth...@medic.gu.se.
It has been suggested that the up-regulation of the tumour suppressor
p16 gene and induction of senescence protect the phenotype of psoriatic
involved skin from malignant transformation. On the other hand, Id1,
which is inversely correlated with p16 has been shown to be
up-regulated in psoriatic involved skin. To test the hypothesis that
there may be an altered regulation of p16 in psoriatic involved skin,
we have measured genes involved in the Igf-1 receptor signalling
through the Ras/MAPK cascade. Igf-1R, IGFBP3, hRas, Ets2, JunB, Egr-1,
Id1, MIDA1 and p16 gene expressions were measured using quantitative
real-time PCR in total RNA isolated from punch biopsies from psoriatic
involved (n=9) and uninvolved skin (n=9) and from cutaneous squamous
cell cancer (SCC) involved (n=8) and uninvolved skin (n=8). The IGFBP3,
hRas, JunB, Egr-1, Id1 and MIDA1 genes were up-regulated in psoriatic
involved skin compared with uninvolved skin. The p16, JunB and MIDA1
genes were up-regulated in SCC involved skin compared with uninvolved
skin. Our results indicate that there may be a balance between the
proliferation and induction of senescence in psoriasis. This balance
may vary and the psoriatic involved skin represented in this study
appears to be in a proliferative state rather than senescence.
Furthermore, we suggest that the noted up-regulation of JunB, which has
been shown to up-regulate p16, in combination with the previously
reported elevation of p16 expression in psoriatic involved skin, may
indicate activation of a pathway by which JunB may protect the
psoriatic plaque by inducing p16 in an event of malignant stress.
PMID: 16552541
Mitogen- and Stress-Activated Protein Kinase 1 Is Activated in Lesional
Psoriatic Epidermis and Regulates the Expression of Pro-Inflammatory
Cytokines.
Funding AT, Johansen C, Kragballe K, Otkjaer K, Jensen UB, Madsen MW,
Fjording MS, Finnemann J, Skak-Nielsen T, Paludan SR, Iversen L.
1Department of Dermatology, Aarhus Sygehus, Aarhus University Hospital,
Aarhus C, Denmark.
Mitogen- and stress-activated protein kinase 1 (MSK1) is a downstream
target of both the p38 and extracellular signal-regulated kinase 1/2
(ERK1/2) mitogen-activated protein kinases (MAPKs). MSK1 stimulates
transcription of different pro-inflammatory genes through activation of
transcription factors. The purpose of this study was to investigate the
expression and activation of MSK1 in lesional psoriatic skin and its
role in cytokine production in cultured normal human keratinocytes.
Western blotting revealed a consistent and significant increase in
phosphorylated (activated) MSK1(Ser376) in lesional psoriatic skin.
Immunofluorescence staining revealed the phosphorylated MSK1(Thr581) to
be localized in the basal layers of the epidermis in lesional psoriatic
skin. No staining was found in non-lesional psoriatic skin. Cultured
human keratinocytes incubated with anisomycin or IL-1beta resulted in
the phosphorylation of the p38 MAPK and MSK1(Ser376). MSK1(Ser376)
phosphorylation was inhibited by pre-incubation with the p38 inhibitor
SB 202190. Transfection of the keratinocytes with specific MSK1 small
interfering RNA resulted in 80% reduction of MSK1 expression and 51,
40, and 31% decrease in IL-6, IL-8, and tumor necrosis factor-alpha
protein production, respectively. This study demonstrates for the first
time the expression of MSK1 in epidermal keratinocytes and increased
activation focally in psoriatic epidermis. As MSK1 regulates the
production of pro-inflammatory cytokines, it may play a role in the
pathogenesis of psoriasis.Journal of Investigative Dermatology advance
online publication, 16 March 2006; doi:10.1038/sj.jid.5700252.
PMID: 16543895
This pathway is being tested as we speak.
MSK1 brings us back to c-fos and AP-1,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16532028
Mitogen- and stress-activated protein kinase 1 is critical for
interleukin-1-induced, CREB-mediated, c-fos gene expression in
keratinocytes.
Schiller M, Bohm M, Dennler S, Ehrchen JM, Mauviel A.
[1] 1INSERM U697, Hopital Saint-Louis, Paris, France [2] 2Department of
Dermatology, Ludwig Boltzmann Institute for Cell Biology and
Immunobiology of the Skin, University of Munster, Munster, Germany.
c-fos, which encodes a transcription factor of the AP-1 family, is a
prototypical immediate-early gene induced by a number of
proinflammatory cytokines including interleukin-1 (IL-1), the latter
being an important regulator of skin homeostasis. Using the human
keratinocyte cell line HaCaT as an in vitro model, we dissected the
molecular pathways leading to IL-1-induced c-fos gene induction.
Phosphorylation of the transcription factor cAMP response element
binding protein (CREB) at Ser133 was found to be essential for
IL-1-induced c-fos gene induction and was closely paralleled by protein
kinase A (PKA) activation. In contrast to other cell types, the
cyclooxygenase/prostaglandin pathway, known to activate the cAMP/PKA
cascade, plays little, if any, role in c-fos expression downstream of
the IL-1 receptor in keratinocytes. Simultaneous activation of several
of the mitogen-activated protein kinase (MAPK) cascades occurred in
response to IL-1, but each differentially contributed to c-fos
induction by IL-1, with the p38/MAPK being the most crucial of all, the
extracellular signal-regulated kinase pathway contributing in an
additive manner and the Jun N-terminal kinase pathway playing little,
if any, role. We also demonstrate that p38-dependent activation of
mitogen- and stress-activated kinase 1 (MSK1), a CREB kinase, is a key
step for c-fos gene activation by IL-1. Finally, we identify MSK1 as
playing a positive role in the control of cell proliferation of both
HaCaT keratinocytes and the A431 human epidermoid carcinoma
line.Oncogene advance online publication, 13 March 2006;
doi:10.1038/sj.onc.1209479.
PMID: 16532028
This next abstract is important as it shows that P doesn't need
something floating
around systemic wide to act as a trigger. Or does it?
The Vast Majority of CLA+ T Cells Are Resident in Normal Skin.
Clark RA, Chong B, Mirchandani N, Brinster NK, Yamanaka KI, Dowgiert
RK, Kupper TS.
Department of Dermatology, Brigham and Women's Hospital and Harvard
Skin Disease Research Center, Boston, MA 02115.
There are T cells within normal, noninflamed skin that most likely
conduct immunosurveillance and are implicated in the development of
psoriasis. We isolated T cells from normal human skin using both
established and novel methods. Skin resident T cells expressed high
levels of CLA, CCR4, and CCR6, and a subset expressed CCR8 and CXCR6.
Skin T cells had a remarkably diverse TCR repertoire and were mostly
Th1 memory effector cells with smaller subsets of central memory, Th2,
and functional T regulatory cells. We isolated a surprising number of
nonexpanded T cells from normal skin. To validate this finding, we
counted T cells in sections of normal skin and determined that there
are approximately 1 x 10(6) T cells/cm(2) normal skin and an estimated
2 x 10(10) T cells in the entire skin surface, nearly twice the number
of T cells in the circulation. Moreover, we estimate that 98% of CLA(+)
effector memory T cells are resident in normal skin under resting
conditions. These findings demonstrate that there is a large pool of
memory T cells in normal skin that can initiate and perpetuate immune
reactions in the absence of T cell recruitment from the blood.
PMID: 16547281
Now this is an area that deserves deePer understandings. I take my fish
oils and
flax seed oils everyday. Am i helping or hurting these pathways?
Psoriasis is associated with lipid abnormalities at the onset of skin
disease.
Mallbris L, Granath F, Hamsten A, Stahle M.
King Gustaf V Research Institute, Department of Medicine, Karolinska
Institutet, Stockholm, Sweden. lotus.m...@medks.ki.se
BACKGROUND: Psoriasis appears to have increased cardiovascular
morbidity. The underlying pathogenetic mechanisms remain unclear.
Multiple factors, including systemic inflammation, oxidative stress,
aberrant lipid profile, and concomitant established risk factors, have
been discussed. However, previous studies consist of heterogeneous
patient materials, including persons with highly varying disease
duration and treatment. METHODS: Two-hundred patients were investigated
at the onset of psoriasis, comparing plasma concentrations of lipids,
lipoproteins, and apolipoproteins with those of matched controls (N =
285). RESULTS: Psoriasis patients manifest significant lipid
abnormalities. Specifically, patients had significantly higher
cholesterol concentrations in the very-low-density lipoprotein and
high-density-lipoprotein fractions. Adjustment for established
environmental risk factors did not affect the results. LIMITATION: The
response rate among control subjects was low. However, an additional
analysis of a random subset of nonresponders demonstrated no
substantial differences in the main results. CONCLUSION: The study
supports the notion that lipid abnormalities in psoriasis may be
genetically determined rather than acquired.
PMID: 16546581
One thing is for sure. If I eat soy bean oil everyday i will increase
my P till my
head blows uP!!! And that's why i hate the stuff...
Analysis of IFN-kappa Expression in Pathologic Skin Conditions:
Downregulation in Psoriasis and Atopic Dermatitis.
Scarponi C, Nardelli B, Lafleur DW, Moore PA, Madonna S, De Pita O,
Girolomoni G, Albanesi C.
Laboratory of Immunology and Allergology, Istituto Dermopatico
dell'Immacolata (IDI)-IRCCS, Rome, Italy.
Interferon-kappa (IFN-kappa) is a type I IFN expressed by
keratinocytes, monocytes and dendritic cells (DCs). In human
keratinocytes, it is produced in response to double-stranded RNA
(dsRNA) and other IFNs and protects from viral infections. In monocytes
and DCs, IFN-kappa induces tumor necrosis factor-alpha (TNF-alpha) and
interleukin-10 (IL-10) and inhibits lipopolysaccharide (LPS)-induced
IL-12. In this study, we evaluated IFN-kappa expression in skin lesions
of patients with common immune-mediated inflammatory disorders using
immunohistochemical techniques. IFN-kappa was not detectable in healthy
skin but was strongly expressed in allergic contact dermatitis and
lichen planus-affected skin. IFN-kappa was localized mainly in basal
and suprabasal keratinocytes and in some leukocytes infiltrating the
dermis. In contrast, IFN-kappa expression in psoriatic or atopic
dermatitis (AD) pidermis was weak and detectable in only 2 of 5
patients examined. Consistently, cultured keratinocytes and monocytes
obtained from psoriatic and AD patients expressed null or low levels of
IFN-kappa in response to IFN-gamma, which strongly upregulates
IFN-kappa in normal keratinocytes. IFN-kappa accumulated in
keratinocyte cytoplasm and plasma membrane, and only limited amounts
were released extracellularly. Soluble IFN-kappa did not influence
keratinocyte proliferation or chemokine and membrane molecule
expression, and only its membrane-associated form activated
IFN-stimulated response element (ISRE) signaling. Given the difference
in IFN-kappa expression levels in the skin disorders examined,
IFN-kappa presence or deficiency might have different pathogenetic
consequences depending also on other disease-specific intrinsic
alterations.
PMID: 16542135
-----------------------------------------------------------------------------------------
randall....fish or not, i'm not gonna stoP eating it! But rubbing it in
the skin?
randall
New inflammation pathway?
May be. Will it help to cure us? We can only hoPe and Pray for that
day...
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16469707
p120-catenin mediates inflammatory responses in the skin.
Perez-Moreno M, Davis MA, Wong E, Pasolli HA, Reynolds AB, Fuchs E.
Laboratory of Mammalian Cell Biology and Development, Howard Hughes
Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Although p120-catenin regulates adherens junction (AJ) stability in
cultured cells, genetic studies in lower eukaryotes have not revealed a
role for this protein in vivo. Using conditional targeting in mice, we
show that p120 null neonatal epidermis exhibits reduced intercellular
AJ components but no overt disruption in barrier function or
intercellular adhesion. As the mice age, however, they display
epidermal hyperplasia and chronic inflammation, typified by hair
degeneration and loss of body fat. Using skin engraftments and
anti-inflammatory drugs, we show that these features are not
attributable to reductions in junctional cadherins and catenins, but
rather NFkB activation. Both in vivo and in vitro, p120 null epidermal
cells activate nuclear NFkB, triggering a cascade of proinflammatory
NFkB targets. Although the underlying mechanism is likely complex, we
show that p120 affects NFkB activation and immune homeostasis in part
through regulation of Rho GTPases. These findings provide important new
insights into p120 function.
PMID: 16469707
So, I went looking for P120. Nice that they called it that? We all want
to live
to 120 but not with P. hehe
http://www.nature.com/nrm/journal/v7/n4/full/nrm1916.html
Inflammation: Linear relationships
by
Ekat Kritikou
The protein p120 is a conserved member of the Armadillo-repeat family
of catenins. Although its roles in regulating adherens-junction
stability and the activities of small Rho-family GTPases have been
studied in vitro, the physiological importance of this protein in vivo
has remained unclear. Perez-Moreno et al. now provide important
insights into the function of p120 by showing that it mediates
inflammatory responses in the skin.
(Damn! I knew it looked like armadillo skin!)
In an attempt to investigate the role of p120 in vivo, the authors
generated p120 conditional-skin knockout mice (cKO). To their surprise,
they found that even though the cKO epidermis showed reduced levels of
intercellular adherens-junction components this was not accompanied by
a disruption of epidermal integrity and barrier function. With ageing,
cKO mice had classic features of chronic subcutaneous inflammation,
including hair disintegration, muscle wasting, hyperplasia and enhanced
vasculature - phenotypic abnormalities that distinguished them from
their wild-type counterparts.
To explore whether the observed hyperplasia and hair-loss phenotypes
were a cause or a consequence of the associated inflammatory skin
disease, the authors carried out skin-graft experiments on
immunocompromised nude mice. They treated animals with dexamethasone
- a potent immunosuppressant - and were able to, in fact, identify
a causal role for inflammation in hair loss and hyperproliferation, in
a way that seemed to be independent of intercellular adhesion. As
dexamethasone treatment exerts its effects partly by inactivating
nuclear factor-kappaB (NF-kappaB) signalling, the authors evaluated the
status of NF-kappaB activity in both cKO skin and keratinocytes. The
overall NF-kappaB protein levels were similar in wild-type and
p120-null epidermis, but in p120-null epidermis there was a sustained
activation of NF-kappaB activity, which was accompanied by increased
levels of downstream targets of this pathway including several
inflammatory cytokines.
But how does the loss of p120 lead to NF-kappaB activation? Given
p120's previously postulated role in the regulation of small GTPases,
the authors investigated whether the activity of Rho might be altered
in the absence of p120. Indeed, in the absence of p120, RhoA activity
was enhanced and was associated not only with altered
cytoskeletal-membrane dynamics, but also with NF-kappaB activation.
The authors proposed a model in which p120 functions upstream of RhoA
activation, which is upstream of NF-kappaB activation, which, in turn,
regulates the expression of several cytokines resulting in an
inflammatory skin disease.
These findings provide new insights into why reductions in p120 have
been associated with epithelial hyperproliferation and tumorigenesis,
and they open new avenues for exploring the relationship between
intercellular adhesion molecules, small GTPases and inflammatory events
that are a hallmark of several human skin disorders.
links
http://www.rockefeller.edu/labheads/fuchs/intro.php
***************************************************************************
Whats RhoA,
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
Why don't we look at some of the old P pathways. Here's a few of the
one's I wish
I could turn off. Well... The p part of them, not the part that we
need. Duh.
First you have to know, We psoriatics take the Th1 (T helper Cell 1)
pathways,
http://www.biocarta.com/pathfiles/h_dcPathway.asp
Then CLA turns on MHCII.
Turning on MHCII
http://www.biocarta.com/pathfiles/h_CSKPathway.asp
Thats the basic. We all have pathways that vary according to the YMMV
theory.
Some of those.
Vitamin D receptor-- pathway (biocarta)
http://www.biocarta.com/pathfiles/h_vdrPathway.asp
The vitamin D receptor, VDR is the mediator of all genomic actions of
vitamin D3 and its analogs. It belongs to a family of ligand induced
transcription factors, nuclear receptors (NRs). Vitamin D3 is the main
regulator of calcium homeostasis and is critical in bone formation. It
is also involved in controlling cellular growth, differentiation and
apoptosis, which makes synthetic vitamin D3 analogues interesting for
therapy of such diseases as cancer and psoriasis. <sniP>
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
The eicosanoids (arachidonic acid) are a good pathway for P
inflammation.
http://www.biocarta.com/pathfiles/h_eicosanoidPathway.asp
The eicosanoids are a family of lipophilic hormones derived from the
twenty carbon fatty acid arachidonic acid. Although they are diverse in
structure, many eicosanoids have roles in inflammation, including
regulation of vasodilation, vascular permeability, pain, and
recruitment of leukocytes. Most members of this family are rapidly
metabolized near their site of synthesis, so they act locally on
neighboring cells, not distant parts of the body. They are also not
stored in cells, but synthesized rapidly in response to stimuli, making
regulation of their synthesis a key to their activity. Many drugs act
through modulating the production of eicosanoids or modulating their
signaling pathways. Hormones in the eicosanoid family include the
prostaglandins, thromboxanes, leukotrienes, and prostacyclins. The
first step in the production of eicosanoids is the release of
arachidonic acid from either diacylglycerol or phospholipids by
membrane bound phospholipases in response to extracellular stimuli.
Arachidonic acid has several possible fates, including oxygenation by
lipoxygenases to make HPETEs (hydroperoxy-eicosatetraenoic acids), or
production of prostaglandin H2 by PGH2 synthase. 5-lipoxygenase acts
with the membrane bound protein FLAP (five lipoxygenase activating
protein) to produce the epoxide leukotriene LTA4 which is hydrolyzed to
produce LTB4 or has glutathione added by a glutathione S-transferase to
produce LTC4 and LTD4. A G-protein coupled receptor for LTD4, CysLT1,
mediates an important component of the inflammatory response of
leukotrienes on airway constriction and recruitment of leukocytes, and
several marketed asthma drugs act as antagonists of the CysLT1
receptor. PGH2 synthase actually consists of two enzyme components, a
cyclooxygenase and a peroxidase, and there are more than one type of
cycloxygenase, including Cox-1 and Cox-2. Recent NSAIDS acting
selectively as Cox-2 inhibitors like Vioxx are widely used for the
treatment of arthritis and other inflammatory conditions, inhibiting
the production of downstream thromboxanes and prostaglandins. PGH2 also
has several possible fates, including conversion by thromboxane
synthase to Tpx2, an eicosinoid with potent coagulation and
vasoconstriction activity. PGI2, or prostacyclin, synthesized by
prostacyclin synthase, has properties opposite those of thromboxane,
causing vasodilation and a reduction in clotting through the IP
receptor, causing thromboxanes and PGI2 to act in opposition to each
other. Thromboxane antagonists and prostacyclin agonists both provide
tools and drugs to reduce vasoconstriction. The prostaglandins include
PGD2, PGE2 and PGF2, with varying degrees of selectivity among their
receptors, DP, EP and FP, respectively. PGE2 exerts biological effects
including induction of pain, fever and vasodilation through at least
four receptors, EP1, EP2, EP3 and EP4, and EP3 is found in multiple
splice variants. The diversity of the eicosanoids and their receptors
and their involvement in many disease states makes it likely that this
pathway will continue as a major research focus.
----------------------------------------------------------------------------
And then the PPARs are turned on by AA.
http://www.biocarta.com/pathfiles/h_pparaPathway.asp
The most recognized mechanism by which peroxisome proliferators
regulated gene expresssion is through a PPAR/RXR heterodimeric complex
binding to a peroxisome proliferator-response element (PPRE) (classical
mechanism). However, there are the possibility of several variations on
this theme: 1). The peroxisome proliferator interacts with PPAR that
preexists as a DNA complex with associated corepressors proteins. The
interaction with ligand causes release of the corepressor and
association with a coactivator, resulting in the classical mechanism.
2). The peroxisome proliferator interacts with PPAR as a soluble member
of the nucleus. The binding of ligand results in RXR
heterodimerization, DNA binding and coactivator recruitment. 3). In
this scenario, PPAR exists in the cytosol, perhaps complexed to heat
shock protein 90 and/or other chaperones. Binding of peroxisome
proliferator causes a conformational change and translocation into the
nucleus. Scenarios 4 and 5 require regulation of gene expression via
non-classical mechanisms: 4). PPAR is capable of interacting with, and
forming DNA binding heterodimers with, several nuclear receptors
including the thyroid hormone receptor. The binding site for this
non-RXR heterodimer need not be the classic DR-1 motif found in the
PPRE. 5). PPAR may participate in the regulation of gene expression
witout binding to DNA. By association with transcription factors such
as c-jun or p65, PPAR diminishes the ability of AP1 or NFB to bind to
their cognate DNA sequences, respectively. Also shown in this scheme
are two means to modify the peroxisome proliferator response. Most
importantly, growth factor signaling has a pronounced affect on PPAR
via post-translational modification. PPAR is a phosphoprotein and its
activity is affected by insulin. Several kinase pathways affects
PPARa's activity, although the specific kinases and phosphorylation
sites have not been conclusively determined.
***********************************
This next pathway, IL-10 is one i've fooled around with to try and dial
in a lowering
of the Th1 skew.
http://www.biocarta.com/pathfiles/h_il10Pathway.asp
So we have to be carefull as we don't know what the antigen is,
http://www.biocarta.com/pathfiles/h_tcrPathway.asp
Chances are if you can clear up on the pagano (vegetarian diets) then
the
fats play a large role in your (ymmv) type of P.
note:: quite a bit is left out, in particular that part that isn't
known yet. ;-(
randall.... what type of P do you have?
randall
So we have funky skin for two different reasons. Are they both due to
allergy? What about th1 and th2 skin eruPtions?
And what does worms have to do with all of this?
http://wusa9.com/health/health_article.aspx?storyid=47933
Here's the conventional wisdom: Pets promote allergy, kids shouldn't
eat peanuts until they're at least 3, and intestinal worms are nothing
more than an icky reminder of life before flush toilets.
Here's the new wisdom: Early exposure to pets, peanuts and intestinal
worms might actually be good for you, because they program the
developing immune system to know the difference between real threats,
such as germs, and Aunt Millie's cat.
[...]
As high-risk as the trial is, it might be extremely rewarding, doctors
say. Each year in the USA, about 15,000 people suffer severe allergic
reactions from eating peanuts, and about 100 die.
"It's the first large-scale trial of what we consider a very dangerous
allergic food," Ownby says.
To the squeamish, it might not matter that intestinal worms are less
risky than foods that promote allergy. But some doctors say worms might
do something that allergy-causing substances won't do - broadly reset
the immune system so that it no longer reacts to allergy-causing
substances or attacks the body's tissues, as it does in Crohn's disease
and Type I diabetes. "This is an exciting new area with potential for
opening new therapeutic avenues for diseases that are hard to control
and treat," says Weinstock of Tufts New England Medical Center.
Worms captured Weinstock's imagination and that of his collaborator,
David Elliott of the University of Iowa, because worm infections appear
to regulate the immune system so that it functions normally. The
allergic response - itchy, watery eyes, a runny nose and constriction
of smooth muscles - evolved to flush out intestinal worms. "The
immune system didn't evolve for allergy," Weinstock says. "Why in a
hundred billion years of evolution would we evolve a response for
allergy?"
In fact, says Robert Coffman, vice president of the biotech firm
Dynavax Technologies, the immune system developed two sets of
responses: one for bacteria and viruses and one for worms. Called Th1
for germs and Th2 for worms, they work in opposition. When Th1 is
active, Th2 takes a break. When Th2 is active, it's Th1's turn. All of
the symptoms people link with allergy are part of the Th2 response.
The worm turns
Weinstock, Elliott and other researchers believe that a low-grade
infection with intestinal worms - pig whipworms because they can't
reproduce in people - can restore the immune system's natural
balance. A small-scale study in which 29 people with Crohn's disease
drank whipworm eggs in Gatorade found that 23 responded to treatment
and 21 of the 23 experienced complete remission.
Although worms haven't been directly tested in allergic patients,
researchers point to a study by Maria Yazdanbakhsh of Leiden University
in the Netherlands, which found that treating schoolchildren in Gabon
for worms, so that the worms were expelled from their bodies, doubled
their risk of becoming allergic to house dust mites, a common allergen.
Weinstock argues that it is exposure to the worms in the environment
that confers protection against allergies. "That's one possibility," he
says. "Whether it's due to worms, endotoxin, lifestyle, smoking or
other factors that we haven't identified - that's the fun of it. But
environment clearly plays a part."
***********************************************
Who is this dude?
http://www.tufts-nemc.org/medicine/gastro/Weinstock.htm
Lets find Weinstocks abstracts to get the scientific explanation.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16393954
Heligmosomoides polygyrus induces TLR4 on murine mucosal T cells that
produce TGFbeta after lipopolysaccharide stimulation.
Ince MN, Elliott DE, Setiawan T, Blum A, Metwali A, Wang Y, Urban JF
Jr, Weinstock JV.
Department of Internal Medicine, Division of Gastroenterology and
Hepatology, University of Iowa, Carver College of Medicine, Iowa City,
IA 52242, USA. m-nedi...@uiowa.edu
Helminths are immune modulators that down-regulate colitis in
inflammatory bowel disease. In animal models, intestinal bacteria drive
colitis and in humans certain alleles of the LPS receptor protein TLR4
increase inflammatory bowel disease susceptibility. To understand
helminthic immune modulation in the gut, we studied the influence of
intestinal Heligmosomoides polygyrus colonization on LPS-induced lamina
propria mononuclear cell (LPMC) cytokine responses in mice. LPS did not
stimulate TGFbeta production from LPMC of uninfected mice. LPS strongly
induced LPMC from worm-infected animals to secrete TGFbeta, but not
TNF-alpha or IL-12. The TGFbeta derived from mucosal T cells. Helminth
infection up-regulated TLR4 expression only in lamina propria T cells.
LPMC from worm-infected TLR4 mutant animals did not respond to LPS,
suggesting that LPS required TLR4 to stimulate TGFbeta secretion. Thus,
during helminth infection, LPS challenge induces mucosal T cells to
make TGFbeta through a TLR4-dependent process without promoting
synthesis of proinflammatory cytokines.
PMID: 16393954
If we had some apoptosis then the P would vanish?
http://www.rndsystems.com/cb_detail_objectname_SU04_AktModulates.aspx
We know that IL-10 and TGF-beta, go along with Th2 Atopic dermatitis,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16387603
TGF-beta also takes part in the Th2 condition called cancer,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16363062
PSORIASIS IS A TH1 condition. Yet we've had folks diagnosed with P, but
sounding like they may have something else recently. A Th2 atopic
dermatitis to be exact.
While far fewer th2 cells reside in the skin only 2% of the poPulation
gets the dreaded
P.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16547281
Is P it a big Pretender or what? Due to allergy?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15186319
Granulocyte colony-stimulating-factor-induced psoriasiform dermatitis
resembles psoriasis with regard to abnormal cytokine expression and
epidermal activation.
Mossner R, Beckmann I, Hallermann C, Neumann C, Reich K.
Department of Dermatology, Georg-August-University Gottingen, Germany.
Psoriasis is a chronic inflammatory skin disorder characterized by
accumulation of Th1-type T cells and neutrophils, regenerative
keratinocyte proliferation and differentiation, and enhanced epidermal
production of antimicrobial peptides. The underlying cause is unknown,
but there are some similarities with the immunologic defense program
against bacteria. Development of psoriasiform skin lesions has been
reported after administration of granulocyte colony-stimulating factor
(G-CSF), a cytokine induced in monocytes by bacterial antigens. To
further investigate the relation between this type of cytokine-induced
dermatitis and psoriasis, we analyzed the cutaneous cytokine profile
[tumor necrosis factor-alpha (TNF-alpha), interferon-gamma,
transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10),
IL-12p35 and p40, and IL-8] and expression of markers of epidermal
activation [Ki-67, cytokeratin-16, major histocompatibility complex
(MHC) class II, intercellular adhesion molecule-1 (ICAM-1)] in a
patient who developed G-CSF-induced psoriasiform dermatitis by using
quantitative real-time reverse transcriptase-polymerase chain reaction
and immunohistology. The histologic picture resembled psoriasis with
regard to epidermal hyperparakeratosis and the accumulation of
lymphocytes in the upper corium. CD8(+) T cells were found to
infiltrate the epidermis which was associated with an aberrant
expression of Ki-67, cytokeratin-16, MHC class II, and ICAM-1 on
adjacent keratinocytes. As compared to normal skin (n = 7), there was
an increased expression of TNF-alpha, IL-12p40, and IL-8, a decreased
expression of TGF-beta1, and a lack of IL-10, similar to the findings
in active psoriasis (n = 8). Therefore, G-CSF may cause a lymphocytic
dermatitis that, similar to psoriasis, is characterized by a
pro-inflammatory Th1-type cytokine milieu and an epidermal phenotype
indicative of aberrant maturation and acquisition of non-professional
immune functions.
PMID: 15186319
Looks like P but isn't! Ben and Mike are you taking this in??
Since psoriatics don't have high levels of IL-10 and IL-4 it's a cinch
we won't be gettting
thyroid cancer!!
http://www.therapeuticsdaily.com/news/article.cfm?contentValue=820946&contentType=sentryarticle&channelID=28
Not that it was my first choice to worry about. lol
But if I had to eat worms to have really low levels of P, I may
consider it!
http://groups.google.com/groups/search?q=weinstock+psoriasis&qt_s=Search
H'mmm deja vu, Weinstock has aPPeared here before...
randall...as the worm learns!
Pieter
>To the squeamish, it might not matter that intestinal worms are less
>risky than foods that promote allergy. But some doctors say worms might
>do something that allergy-causing substances won't do - broadly reset
>the immune system so that it no longer reacts to allergy-causing
>substances or attacks the body's tissues, as it does in Crohn's disease
>and Type I diabetes. "This is an exciting new area with potential for
>opening new therapeutic avenues for diseases that are hard to control
>and treat," says Weinstock of Tufts New England Medical Center.
So now you've invented a real cure:
Eat worms! This one may actually work. But I do expect some side
effects like itch moving to other places.
Pieter
randall
Pieter wrote:
<sniP>
>
> So now you've invented a real cure:
>
> Eat worms! This one may actually work. But I do expect some side
> effects like itch moving to other places.
Then use that nanObac rectal EDTA vitamin suppository?
P news is rather thin again today....
I'll try anyway.
If you get tee'd off with it, just piss on it*.
http://www.capeargus.co.za/index.php?fSectionId=342&fArticleId=3182834
Don't smoke it*,
http://www.theopenpress.com/index.php?a=press&id=8435
But what causes it*?
Who led the way on this Th1 thinking?
Co-discover of pyrogen (endogenous mucky muck/LPS, lipopolysaccharide
etc ) dies.
Dr. Richard Berlin, associate dean for research planning and
coordination, and head of the Department of Cell Biology at Health
Center, died Feb. 26.
http://www.advance.uconn.edu/2006/060313/06031310.htm
[...]
He held a research fellowship at Johns Hopkins after medical school and
worked with Dr. W. Barry Wood, former vice president of Johns Hopkins
University and hospital, who became a professor of microbiology in the
schools of medicine and hygiene and public health. Wood discovered
endogenous pyrogen, now known as interleukin, and Berlin collaborated
with him on that work. <sniP>
********************************
Whats interleukin? Does it have anything to do with P?
http://www.stjohns.edu/academics/pr_aca_060328.sju
Didn't we have a pic of LPS in the lung a few weeks back?
YeP,
(darn the time expired in the news for it)
Damn! This is headed off in to another randall rant circle jerk.
What? huh?
Lets segue....
Whats for dinner?
It's gonna need sauce.
http://homecooking.about.com/od/condimentrecipes/r/blsauce13.htm
To spicey? Chicken? Not souPy chicken!
randall... NO doubt! It = Sh*t = P!
>
> Pieter
randall
> But what causes it*?
>
> Who led the way on this Th1 thinking?
>
> Co-discover of pyrogen (endogenous mucky muck/LPS, lipopolysaccharide
> etc ) dies.
> Dr. Richard Berlin, associate dean for research planning and
> coordination, and head of the Department of Cell Biology at Health
> Center, died Feb. 26.
> http://www.advance.uconn.edu/2006/060313/06031310.htm
> [...]
> He held a research fellowship at Johns Hopkins after medical school and
> worked with Dr. W. Barry Wood, former vice president of Johns Hopkins
> University and hospital, who became a professor of microbiology in the
> schools of medicine and hygiene and public health. Wood discovered
> endogenous pyrogen, now known as interleukin, and Berlin collaborated
> with him on that work. <sniP>
>
> ********************************
>
> Whats interleukin? Does it have anything to do with P?
>
I couldn't find enough to report on how pyrogen was first discovered
and when. :(
But look at the drugs in the PiPe to treat cytokines.
The logical increase of biologicals,
http://www.genengnews.com/news/bnitem.aspx?name=1205077XSL_NEWSML_TO_NEWSML.xml
Research and Markets (http://www.researchandmarkets.com/reports/c32007)
has announced the addition of Cytokine Therapeutics: Current and Future
Markets in Inflammatory Disease to their offering.
According to this Decision Resources report, inflammatory diseases
affect more than 500 million patients in the major pharmaceutical
markets, and total prevalence is growing. In the treatment of these
diseases, cytokine therapeutic agents play a major role. The five
cytokine agents that have reached the U.S. and European markets so far
have achieved major commercial success: in 2004, the value of the
global anti-inflammatory cytokines market was $6.5 billion. Cytokine
therapeutics may in the future prove useful in the treatment of many
other diseases, but owing to the value of the inflammatory disease
market and the great interest in developing new cytokine therapeutics
to treat inflammatory diseases, this report focuses only on these
indications, describing the role of cytokines in inflammation,
surveying the current market, discussing emerging agents in detail, and
concluding with a comprehensive market outlook.
By 2004, five products that target cytokines, all recombinant agents,
had reached the market; sales of these agents reached $6.5 billion in
that year, primarily for treatment of inflammatory diseases such as
rheumatoid arthritis (RA) and Crohn's disease (CD). Nearly all sales
were generated by the three available anti-TNF-a agents: etanercept,
infliximab, and adalimumab.
Twenty-one recombinant products that target 11 different cytokines are
in clinical development for conditions such as RA, psoriasis, CD,
asthma, multiple sclerosis, and osteoarthritis. A significant number of
orally active, small-molecule inhibitors of cytokine production are
also in clinical development for the same diseases. Development of the
marketed cytokine therapeutics for additional indications is ongoing.
The complexity of cytokines and their receptors has so far hindered the
development of additional cytokine therapeutics, and Decision Resources
expect few agents in development to reach the market before 2010.
Therefore, currently available cytokine therapeutics will face
relatively few challenges from new cytokine therapeutics. However, the
existing agents will face competition from drugs that offer alternative
approaches to the treatment of inflammatory disease, including the
T-cell modulators efalizumab and alefacept and the lymphocyte modulator
abatacept.
Use of the existing cytokine therapeutics in inflammatory indications
will grow significantly through 2009, and a substantial growth in sales
of this drug class is expected. However, assessment of the market
beyond 2009 is difficult owing to the many uncertainties about which of
the newer agents will come to market in 2010 and beyond. Nevertheless,
continuing growth in cytokine therapeutics sales is projected beyond
2010, especially if anti-IL-1 therapy becomes an established treatment
for osteoarthritis.
<sniP>
randall
randall
We've come all the way from IL-1 to MyD88.
http://newswire.rockefeller.edu/?page=engine&id=492
Posted: March 29, 2006
Researchers uncover a pathway linked to autoimmune disease
When a person's immune cells lose the ability to distinguish
"self" from "non-self," they end up launching an attack on the
body they're supposed to protect. Exactly what happens to rob them of
that ability has been the subject of decades of research. In a series
of discoveries that has the potential to help researchers halt
autoimmune disorders - such as lupus and rheumatoid arthritis - one
Rockefeller University scientist has found an underlying mechanism
that begins to explain the pathologies of a
number of immune diseases.
For years, Jeffrey Ravetch, the Theresa and Eugene M. Lang Professor
and head of the Leonard Wagner Laboratory of Molecular Genetics and
Immunology, has been working to untangle the complexities of how the
body turns on itself. He's accumulated evidence that immune cells go
awry in a step-by-step process, and in two papers published in this
month's Journal of Experimental Medicine, he proceeds to nail down
the last few steps by showing that the distribution of a class of
proteins called immunoglobulins, or IgGs, can greatly affect the course
of an autoimmune disease. <sniP>
********************************************************
Are we closer to full understanding of the immune pathways?
Sure hope so.
Abstracts from the last few days.
SLURP-2: A novel cholinergic signaling peptide in human mucocutaneous
epithelium.
Arredondo J, Chernyavsky AI, Jolkovsky DL, Webber RJ, Grando SA.
Department of Dermatology, University of California, Davis, California.
The biologic role of novel cholinergic toxin-like signaling peptides
termed SLURP (secreted mammalian Ly-6/uPAR-related protein) in the
mucocutaneous epithelium is a subject of intense research. Previous
studies demonstrated that SLURP-1 activates the alpha7 subtype of
keratinocyte nicotinic acetylcholine receptors (nAChRs) and facilitates
keratinization and programmed cell death, and that the level of SLURP-2
was found to be upregulated several fold in the hyperproliferative skin
of patients with psoriasis. In this study, we demonstrated for the
first time that human epidermal and oral keratinocytes secrete SLURP-2.
We cloned human SLURP-2 and produced the mouse monoclonal antibody
341F10-1F12 that visualized SLURP-2 in the cytoplasm of normal human
epidermal and oral keratinocytes grown in culture. In epidermis,
SLURP-2 was found predominantly in the suprabasal compartment, whereas
in the attached gingiva-in the lowermost epithelial layers. Recombinant
SLURP-2 (rSLURP-2) competed with nicotinic radioligands for binding to
keratinocytes, showing a higher affinity to the [(3)H]epibatidine- than
[(3)H]nicotine-labeled sites. Treatment with rSLURP-2 significantly (P
< 0.05) increased the number of keratinocytes in culture and their
resistance to apoptosis, which could be abolished by mecamylamine more
efficiently than alpha-bungarotoxin. By real-time PCR and in-cell
western, rSLURP-2 significantly (P < 0.05) downregulated gene
expression of the differentiation markers loricrin, filaggrin, and
cytokeratins 1 and 10, and pro-apoptotic Bax, Bad, and caspase 3 which
were elevated by high extracellular calcium, and rSLURP-2 also
abolished activation of caspases 3 and 8 caused by camptothecin. These
results indicated that SLURP-2 competes with acetylcholine
predominantly at the alpha3 nAChR, and that receptor ligation with
SLURP-2 delays keratinocyte differentiation and prevents apoptosis.
Thus, the different effects observed for SLURP-1 and -2 can be
explained by their differential binding to the nAChR subtypes expressed
in keratinocytes. These findings present a novel paradigm of the
physiologic regulation of mucocutaneous epithelial cells by locally
produced small hormone-like peptide molecules, and open novel
directions toward better understanding and treating of skin and mucosal
diseases. J. Cell. Physiol. (c) 2006 Wiley-Liss, Inc.
PMID: 16575903
Increased endocytic activity in monocyte-derived dendritic cells in
patients with psoriasis vulgaris.
Zhu KJ, Cheng H, Mao XH, Lao LM, Cen JP, Ye J.
Department of Dermatology & Venereology, Sir Run Run Shaw Hospital,
Medical College, Zhejiang University, Hangzhou 310016, People's
Republic of China.
BACKGROUND & OBJECTIVE: The understanding of the pathogenesis of
psoriasis vulgaris has focused on T cell mediated immune disorder for
many years. Recent studies provide evidence that dendritic cells may be
of major importance as regulatory cells driving the psoriasis tissue
reaction, and they are one of the therapeutic targets. In order to
further characterize the role of dendritic cells in psoriasis, this
study was designed to assess the differentiation of dendritic cells
from monocytes (MoDC), the expression of phagocytosis related receptors
by MoDC, their endocytic activity for fluorescent beads and lucifer
yellow as well as their superoxide generation in patients with
psoriasis. METHODS: Twenty eight patients with psoriasis vulgaris and
12 healthy controls were included in the study. MoDC were obtained by
culturing monocytes with granulocyte macrophage-colony stimulating
factor (GM-CSF) and interleukin-4 (IL-4) for 5 days. Cell surface
expression of CD1a, CD14, CD40, CD80, CD83, CD86, HLA-DR, mannose
receptor (MR) and Fcg receptors by MoDC and their endocytosis of
dextran and lucifer yellow were analyzed by flow cytometry. Zymosan
ingestion was measured to access the phagocytosis of MoDC. RESULTS:
Differentiation of monocytes to dendritic cells was upregulated in
patients manifested as significantly increased expression of CD40,
CD80, CD86 and HLA-DR compared with that in healthy controls (P<0.01).
Expression of MR and Fcg receptor II (CD32) by MoDC was significantly
increased in patients with psoriasis as well (P<0.01). Endocytosis of
dextran but not lucifer yellow in patients was significantly higher
than controls (P<0.01), and significantly enhanced phagocytosis by
increasing zymosan ingestion was also observed (P<0.01) in patients.
Taken together, endocytic and phagocytic activity of MoDC in psoriasis
was increased than normal persons. INTERPRETATION & CONCLUSION:
Enhanced activity of dendritic cells binding and capturing foreign
antigens for subsequent antigen presentation and the initiation of
immune responses in psoriasis may contribute to the pathogenesis of the
disease. The upregulated expression of MR and the enhanced endocytic
activity of DC might be an explanation for the absence of skin
infection observed in psoriasis.
PMID: 16567867
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16563649
Apoptosis mediated by cytolytic molecules might be responsible for
maintenance of psoriatic plaques.
Kastelan M, Massari LP, Brajac I.
Department of Dermatovenerology, Rijeka University Hospital Center,
Kresimirova 42, 51000 Rijeka, Croatia.
Psoriasis is a chronic hyperproliferative skin disease characterized by
keratinocyte hyperproliferation and inflammation. It is generally
considered as an autoimmune disease mediated by T cells. The precise
mechanism of triggering keratinocyte hyperproliferation is as yet
unknown. Apoptosis seems to be important in the maintenance of skin
cell homeostasis as well as in the pathogenesis of some skin diseases.
We hypothesize how apoptosis mediated by cytolytic mechanisms could be
involved in initiating and maintenance of psoriatic plaque. Increased
keratinocyte hyperproliferation might develop as a consequence of
failure to remove self-reactive T cells by apoptosis that in other way
cause significant keratinocyte damage. Apoptotic keratinocytes might
trigger an injury response program causing regenerative hyperplasia of
epidermal keratinocytes. Another possibility is that the failure to
eliminate these abnormal keratinocytes could result in the persistence
of chronic inflammatory conditions constantly recruiting specific T
cells. Increased epidermal thickness in psoriasis could be also
explained by imbalance between the expression of pro- and
anti-apoptotic proteins. Epidermal keratinocytes have the ability to
produce cytolytic molecules, thus they might also have the potential to
protect the epidermis from T cell-mediated damage. In conclusion,
hyperproliferation of psoriatic keratinocytes might be partly due to
changes in the keratinocyte expression of pro- and anti-apoptotic
genes, partly to the damaged keratinocytes triggering an inappropriate
wound repair response and partly by the failure to eliminate these
abnormal keratinocytes resulting in the persistence of chronic
inflammation. Each of the proposed mechanisms might be a possible
therapeutic target mainly by new immunomodulatory agents.
PMID: 16563649
PMID: 16552541
randall
randall
randall wrote:
> Hi,
>
> We've come all the way from IL-1 to MyD88.
>
> http://newswire.rockefeller.edu/?page=engine&id=492
>
Forgot a link that went along with myd88,
http://www.jcb.org/cgi/content/abstract/172/7/1057
or
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=16567503
CpG-induced tyrosine phosphorylation occurs via a TLR9-independent
mechanism and is required for cytokine secretion.
Sanjuan MA, Rao N, Lai KT, Gu Y, Sun S, Fuchs A, Fung-Leung WP, Colonna
M, Karlsson L.
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., San
Diego, CA 92121.
Toll-like receptors (TLRs) recognize molecular patterns preferentially
expressed by pathogens. In endosomes, TLR9 is activated by unmethylated
bacterial DNA, resulting in proinflammatory cytokine secretion via the
adaptor protein MyD88. We demonstrate that CpG oligonucleotides
activate a TLR9-independent pathway initiated by two Src family
kinases, Hck and Lyn, which trigger a tyrosine phosphorylation-mediated
signaling cascade. This cascade induces actin cytoskeleton
reorganization, resulting in cell spreading, adhesion, and motility.
CpG-induced actin polymerization originates at the plasma membrane,
rather than in endosomes. Chloroquine, an inhibitor of CpG-triggered
cytokine secretion, blocked TLR9/MyD88-dependent cytokine secretion as
expected but failed to inhibit CpG-induced Src family kinase activation
and its dependent cellular responses. Knock down of Src family kinase
expression or the use of specific kinase inhibitors blocked
MyD88-dependent signaling and cytokine secretion, providing evidence
that tyrosine phosphorylation is both CpG induced and an upstream
requirement for the engagement of TLR9. The Src family pathway
intersects the TLR9-MyD88 pathway by promoting the tyrosine
phosphorylation of TLR9 and the recruitment of Syk to this receptor.
PMID: 16567503
H'mmm?
I think this is big. But i'm gonna need to grow some extra brain cells,
especially
if i'm willing to figure out those last group of abstracts. lol
Here, get a jumP on me,
http://groups.google.com/groups/search?q=myd88+psoriasis&qt_s=Search
Or Tlr's,
http://groups.google.com/groups/search?q=tlr+psoriasis&qt_s=Search
Now, if i only had more time...
randall... and i'll try to SLURp it all uP!
>
JXStern
On 1 Apr 2006 09:45:06 -0800, "randall" <ranh...@aol.com> wrote:
>Hi,
>
>We've come all the way from IL-1 to MyD88.
>
>http://newswire.rockefeller.edu/?page=engine&id=492
>
>Posted: March 29, 2006
>
>Researchers uncover a pathway linked to autoimmune disease
Hey, I like this one very much!
From further along in the article:
"This study puts the last piece of the puzzle in place. Ehlers and
Ravetch found that early on in their life, certain immune cells began
to recognize and react to DNA — something they shouldn’t normally
respond to. That DNA recognition then triggered a three-step process:
A chemical pathway named “toll-like receptor 9” (which signaled with
an adaptor protein called MyD88 and the transcription factor “T-bet”)
led to antibody class-switching to the harmful IgG subclasses that
ultimately lead to the disease. “This begins to explain the
progression of a disease like lupus,” Ravetch says. “And if you block
any step in the pathway, you don’t get the disease.” "
Yeah, OK, but what if you *have* the disease already?
But the "subclass" idea sounds right to me.
Good luck to these guys!
Results may be ten years away, or fifty, but these guys are working
the problem upstream and not just wrapping duct tape around the immune
system after the fact.
J.
randall
Not much worth reporting pertaining directly to P.
Inflammation in general from Boston today.
http://www.boston.com/news/globe/health_science/articles/2006/04/03/inflammation_is_culprit_in_many_ailments/
&
http://www.boston.com/news/globe/health_science/articles/2006/04/03/inflammation_is_culprit_in_many_ailments/?page=2
>From andrea today: http://www.askdrsears.com/html/4/t041700.asp
So! Fight fire with oil in this case. And if that doesn't bring your P
levels down
then pray that you've avoided even worse inflammatory conditions.
And from reading Cruiser's post today. I'm questioning the use of
niacin again.
Does it UNslurP slurp-2 or what?
Did you miss this one cruiser or have been out on the slopes? lol
randall... and once again, can P be comPensatory for these evil things?
randall
Two P news posts in one day!
I'm going for this next one.
http://biz.yahoo.com/prnews/060403/sfm166.html?.v=5
Clinical Study of Drug-Free Psoriasis Treatment Under Way
Monday April 3, 3:28 pm ET
Researchers at Wake Forest University School of Medicine Leading
Investigation of Dermal Advantage(TM)
PORTLAND, Ore., April 3 /PRNewswire/ -- Clinical studies of a drug-free
treatment for psoriasis are under way to investigate the role of a
"medical food" treatment to manage the symptoms of psoriasis, a common,
chronic, inflammatory skin disorder.
Led by Steven Feldman, M.D., Ph.D., and a research team at Wake Forest
University School of Medicine, the study will look at Dermal
Advantage(TM) in a randomized, double-blind trial to analyze the role
of Lactobacillus, or "friendly bacteria," in treating mild to moderate
non-scalp psoriasis. A specific Lactobacillus strain, which is part of
the Dermal Advantage formula, has proven to positively modulate the
gut-triggered inflammatory response in diseases such as inflammatory
bowel disease, Crohn's disease and osteoarthritis. Inflammatory
diseases rely on the same biochemical mechanisms, although they
manifest in vastly different symptoms. Dr. Feldman's research, funded
by the National Psoriasis Foundation, will look for the same positive
effect in relieving psoriasis symptoms.
"We're just beginning to understand the role of the immune system in
many inflammatory diseases," explained Dr. Feldman. "Triggers of
immunity, and eventually inflammation, may occur in the digestive tract
because that is where the body first encounters many new pathogens and
toxins in the food we eat."
According to Gail M. Zimmerman, president and CEO of the National
Psoriasis Foundation, "Clinical studies are not always conducted on
products such as this. We are grateful for the dedication of
researchers like Dr. Feldman to conduct rigorous studies to determine
if this medical food is a beneficial treatment for psoriasis patients."
Study Plan
The study will randomize approximately 40 subjects with mild to
moderate plaque-type psoriasis (less than or equal to 10% body surface
area), who will receive either an active nutritional supplement (Dermal
Advantage) or a placebo. Subjects will take a treatment orally once per
day for 12 weeks. Researchers will assess outcomes including target
lesion assessment, investigator global assessment, pruritus and subject
global assessment.
Need for New Treatments
Current and standard treatments for psoriasis, such as topical
medications and phototherapy, have limitations, and over time psoriasis
tends to resist its treatments. Patients often turn to complementary or
alternative methods for psoriasis treatment. Popular dietary
supplements include: fish oil capsules, evening primrose oil, milk
thistle, oregano oil and shark cartilage.
About Dermal Advantage
Classified as a medical food, Dermal Advantage contains a strain of
bacteria found in many common foods and is defined by the U.S. Food and
Drug Administration as "generally recognized as safe" (GRAS). The
benefits of good bacteria treatments for irritable bowel syndrome,
Crohn's disease and other inflammatory conditions of the intestine are
well-known and documented. However, two years ago, a team of
researchers in Israel hypothesized that the same benefit could be
achieved for non-digestive inflammatory diseases, such as psoriasis.
They were able to ameliorate arthritis in rats using a strain of good
bacteria known to reduce inflammation.
Dermal Advantage, manufactured by Ganeden Biotech, is available at area
retailers. To find a retailer near you, visit Ganeden's Web site at
www.GanedenBiotech.com.
( h'mmm lets see this deal,
http://www.ganedenbiotech.com/index.php?page=Psoriasis
I never thought i'd see the day! )
About Psoriasis
Psoriasis is a noncontagious, genetic skin disease that results when
faulty signals in the immune system prompt skin cells to regenerate too
quickly, causing red, scaly lesions that itch, crack and bleed. It
often affects the elbows, knees, scalp and torso but can appear
anywhere on the body. Ten percent to 30 percent of people with
psoriasis also develop psoriatic arthritis, which causes pain,
stiffness and swelling in and around the joints. There is no cure yet
for these chronic diseases, which can disrupt daily life and are
debilitating for some people.
About the National Psoriasis Foundation
The National Psoriasis Foundation is a patient-driven, nonprofit
organization dedicated to improving the quality of life of more than 5
million Americans diagnosed with psoriasis and/or psoriatic arthritis,
and their families. For more information, contact the Psoriasis
Foundation, headquartered in Portland, Ore., at 800.723.9166, or visit
www.psoriasis.org.
******************************************************
And they have free samples on that link i clicked for this stuff!
randall... time to cozy uP with some good bugs!
randall
Everyday is the same. Flakes and the search for that protein, gene, bug
that may have an inkling of P connectedness.
Here's the susPect du jour.
You know how I feel about Th1 (T helper one cells) being skewed by
the leakage of LPS (endotoxin) from the colon. Or you should know
how i feel. How you should feel about it is easily accomPlished by
drinking to much alcohol and examining the effects on your P lesions.
If they expand, that result may be due to the skewing of the Th1
cells and creation of excess TNF etc.
LPS leads to septicemia in the extreme and the randall hypothesis
calls for only enough to tilt us toward a Th1 profile.
So this next article names a protein. A suspect to examine if you will.
http://www.innovations-report.com/html/reports/life_sciences/report-57507.html
Disruption of a single gene, Nrf2, plays a critical role in regulating
the body's innate immune response to sepsis and septic shock,
according to a study by a research team led by Shyam Biswal, PhD, at
the Johns Hopkins Bloomberg School of Public Health. The researchers
found that the absence of Nrf2 caused a dramatic increase in mortality
due to septic shock in mice. The study's findings, which will be
published in the April 2006 issue of the Journal of Clinical
Investigation, may hold potential for the treatment of life-threatening
sepsis.
Sepsis is a complex disease characterized by an increased inflammatory
response in the body's attempt to combat an infection from
microorganisms such as bacteria, fungi or viruses. A weak host
inflammatory response can lead to greater infection, whereas an
excessive inflammatory response may lead to tissue damage, myocardial
injury, acute respiratory failure, multiple organ failure or death.
Controlling inflammation is thus a central focus of treating sepsis.
Researchers have been hunting for novel host genes that regulate
inflammation as potential targets for the next generation of sepsis
therapies. The incidence of sepsis in the United States ranges from
400,000 to 750,000 cases per year. Mortality due to sepsis is around 30
percent and increases with age from 10 percent in children to 40
percent in the elderly. Mortality is 50 percent or greater in patients
with the more severe syndrome, septic shock.
Suspecting that a dysregulation in the body's inflammatory response
exacerbates sepsis, the research team began looking into the genetic
factors that might contribute to this syndrome. In 2002, Biswal and his
colleagues discovered that Nrf2 acts as a primary regulator of most of
the cellular antioxidant pathways and detoxifying enzymes that protect
the body from a wide variety of environmental toxicants. In subsequent
studies, they discovered that Nrf2 is a pleiotropic protein that
regulates a broad spectrum of genes used by the host to defend against
a variety of stresses, including oxidative and inflammatory diseases
such as cigarette-smoke-inducedemphysema and allergic asthma in mice
models.
Biswal's team found that the deletion of the Nrf2 gene increased the
inflammatory response and caused early death in mice subjected to
septic peritonitis or endotoxin shock or both. Mice deficient in Nrf2
gene expressed dramatically increased levels of effector molecules
(cytokines) that mediate innate immune response, the body's first
line of defense. "Sepsis syndrome is like a speeding car with a brake
failure. Nrf2 may function like a brake that regulates the speed,"
said Biswal, senior author of the study and assistant professor in the
Bloomberg School's Department of Environmental Health Sciences.
Biswal speculates that suboptimal function of Nrf2 may be one reason
why some intensive-care patients progress into severe sepsis and die.
"Nrf2 protects from septic shock by two mechanisms," explained lead
author Rajesh Thimmulappa, PhD, a postdoctoral fellow at Environmental
Health Sciences, Bloomberg School of Public Health. "First, Nrf2
protects from dysregulation of host inflammatory response, which is a
characteristic feature of septic shock. Secondly, Nrf2 protects from
oxidative pathological damage, the main cause of multi-organ failure
during septic shock. Hence, Nrf2 can be a promising therapeutic target
for attenuating septic-related deaths."
According to Biswal, the findings provide a better understanding of the
human body's defense mechanisms to sepsis and septic shock, and may
provide clues to designing novel therapies that could minimize
mortality. The researchers are now trying to find if activation of Nrf2
by a small-molecule drug can minimize pathological damage and improve
survival during sepsis caused by bacteria or viruses. Future studies
will determine the therapeutic potential of targeting Nrf2 for
treatment of sepsis and other inflammatory diseases that impact public
health.
The other coauthors of the study are Hannah Lee, Tirumalai Rangasamy,
Sekhar P. Reddy, Masayuki Yamamoto , Thomas W. Kensler.
This work was supported by NIH grants- HL081205 (S. Biswal), P50
CA058184, NIEHS center grant P30 ES 038819, Young Clinical Scientist
award from Flight Attendant Research Institute (S. Biswal), The
Maryland Cigarette Restitution Fund (S. Biswal); CA94076 (T.W. Kensler)
and P50 HL073994 (S.P. Reddy)".
More information: www.jhsph.edu
******************************************
Low Nrf2 means cancer and high Nrf2 means P? If you have the genes of
course.
I wonder if Th1 guarantee's high Nrf2 levels and Th2 the oPPosite?
Lets look for connections.
http://www.biocarta.com/pathfiles/h_arenrf2Pathway.asp
http://www.nature.com/ncponc/journal/v2/n10/fig_tab/ncponc0319_F2.html
If the psoriatic has excess white adipose tissue (WAT) that pathway
adds to the inflammation of
P. Now we have an explanation via Nrf2,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16581946
Keap 1 recruits Nrf2,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16581765
So for randall's LPS and P theory how does this figure in?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16177082
Lipopolysaccharide-induced heme oxygenase-1 expression in human
monocytic cells is mediated via Nrf2 and protein kinase C.
Rushworth SA, Chen XL, Mackman N, Ogborne RM, O'Connell MA.
Medical Research Council Human Nutrition Research, Elsie Widdowson
Laboratory, Cambridge, United Kingdom.
Monocytes play a key role in mobilization of the immune response during
sepsis. In response to LPS, monocytes produce both proinflammatory
mediators and regulatory proteins that counteract the inflammation and
oxidative stress. In murine macrophages, LPS stimulates expression of
heme oxygenase 1 (HO-1), a cytoprotective enzyme that catalyzes the
degradation of heme. The HO-1 5'-untranslated region, similarly to
other cytoprotective genes, contains antioxidant-response elements
(AREs) that can bind the transcription factor NF-E2-related factor 2
(Nrf2). At present, the role of Nrf2 in LPS-induced HO-1 expression in
monocytic cells has not been investigated. In this study, LPS induced
HO-1 mRNA and protein expression in human monocytes and THP-1 cells.
Nrf2 translocated from the cytosol to the nucleus in response to LPS
and bound to the ARE site in the human HO-1 promoter. In addition, a
dominant negative Nrf2 mutant inhibited LPS-induced HO-1 mRNA
expression but not TNF-alpha mRNA expression in THP-1 cells.
Ro-31-8220, a pan-protein kinase C (PKC) inhibitor, and Go6976, a
classical PKC inhibitor, blunted LPS-induced HO-1 mRNA expression in
monocytes and THP-1 cells. Both PKC inhibitors also blocked LPS-induced
Nrf2 binding to the ARE. These results indicate that LPS-induced HO-1
expression in human monocytic cells requires Nrf2 and PKC.
PMID: 16177082
If the last one makes sense for P, this one makes much more!
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15740980
Super-induction of HO-1 in macrophages stimulated with
lipopolysaccharide by prior depletion of glutathione decreases iNOS
expression and NO production.
Srisook K, Cha YN.
Department of Pharmacology and Toxicology, College of Medicine, Inha
University, Incheon, Republic of Korea.
In the LPS-stimulated macrophages undergoing oxidative burst,
intracellular storage of glutathione (GSH) is depleted, expression of
iNOS is enhanced, and NO is overproduced. In response to the depletion
of GSH, expression of HO-1 is induced and HO activity is elevated.
Thus, in macrophages treated with LPS, productions of NO and CO,
catalyzed, respectively, by accumulated iNOS and HO-1, are increased in
sequence [Biochem. Pharmacol. 68 (2004) 1709]. In support of this, HO-1
is induced in macrophages treated only with buthionine sulfoximine
(BSO), an inhibitor of GSH biosynthesis depleting the GSH level.
Alternatively, when the macrophages were exposed to spermine NONOate,
an exogenous NO-donor, HO-1, was induced also. When the GSH-depleted or
BSO-pretreated macrophages were exposed to NO, delivered either
exogenously from spermine NONOate or endogenously from LPS-derived
elevation of iNOS, super-induction of HO-1 was observed. Moreover, both
the BSO and LPS treatments increased the accumulation of HO-1 inducing
redox-sensitive transcription factor Nrf2 in the nuclear protein
fraction. Thus, when the depletion of GSH is combined with NO delivery,
expression of HO-1 is enhanced to a greater extent than that enhanced
either by GSH depletion or by NO delivery. In these macrophages with
super-induced HO-1 and elevated HO activity, LPS-derived increase in
iNOS expression was down-regulated and NO production was suppressed.
This indicated that induction of HO-1 caused by the NO overproduced
from up-regulated iNOS, in turn, produces a causative inhibition on
iNOS expression and NO production. Thus, it appears that there is a
reciprocal cross-talk between inductions of HO-1 and iNOS in
macrophages stimulated with LPS leading to their survival.
PMID: 15740980
If there is something here,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein&cmd=search&term=nrf2+psoriasis
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide&cmd=search&term=nrf2+psoriasis
Who knows without looking?
***********************************
Whats new in the abstract world and P?
How timely!
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16581564
Interferon-gamma-induced 15-lipoxygenase-2 expression in normal human
epidermal keratinocytes and a pathogenic link to psoriasis vulgaris.
Setsu N, Matsuura H, Hirakawa S, Arata J, Iwatsuki K.
Department of dermatology, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1,
Okayama 700-8558, Japan.
Epidermal keratinocytes contain 15-lipoxygenase, which generates
15-hydroxyeicosatetraenoic acid, a major metabolite of arachidonic
acid. Although two isozymes, 15-lipoxygenase-1 and -2, exist, it
remains unclear which isozyme plays an important role in inflammatory
processes and proliferative skin diseases. In the present study, we
demonstrated that 15-lipoxygenase-2 expression was increased in normal
human epidermal keratinocytes and HaCaT cells treated with
interferon-gamma (200 U/ml), while no induction of 15-lipoxygenase-1
was observed. Under the same culture conditions, no 15-lipoxygenase-2
was expressed by a carcinoma cell line, A431. Weak expression of
15-lipoxygenase-2 was observed in the basal cell layer of non-lesional
psoriatic skin by in situ hybridization and immunostaining, whereas
strong expression of 15-lipoxygenase-2 was observed in all living
layers of psoriatic lesions. Actinic keratosis and squamous cell
carcinomas showed a variable immunostaining pattern for
15-lipoxygenase-2. These results indicate that 15-lipoxygenase-2 is
implicated in interferon-gamma-induced inflammatory processes in normal
human epidermal keratinocytes and psoriatic skin.
PMID: 16581564
15-lox and 15-hete haven't been around in awhile.
Cruiser time to figure all of this in to your hypoxia gig.
randall... all kinds of things are rearing their heads AGAIN.
randall
YOU say tomato, i say TOMATO.
POTATO, potato, & both being nightshades!
Deadly?
Do they flare psoriatics? Once again YMMV!
What marches on?
New research and wouldn't you just know, it would be Italian!
http://www.nutraingredients-usa.com/news/ng.asp?n=66846-lyc-o-mato-tomato-inflammation
Tomato juice could lower inflammation
By Stephen Daniells
4/4/2006 - Italian researchers have reported that a daily glass of
tomato juice could lower markers for inflammation by over 30 per cent,
but has no effect on the immune system, adding to the debate as to
whether carotenoids can boost immune function.
Researchers from the University of the Milan found that a daily intake
of the commercial tomato drink, Lyc-o-Mato was linked to a drop in the
inflammatory mediator TNF-alpha by 34 per cent after six weeks of
supplementation of a normal diet.
Inflammation is linked to hardening of the walls of the arteries
(atherosclerosis), and cardiovascular disease (CVD) - the cause of
almost 50 per cent of deaths in Europe.
Tomato extract contains a mix of potent antioxidants including
lycopene, beta-carotene, vitamin E and various other phytonutrients.
The extract has been associated with lowering blood pressure and
boosting immune function, although this last claim is hotly disputed by
conflicting results.
"We report modest effects of the regular uptake of a tomato drink
providing small amounts of carotenoids on the production of
inflammatory mediators such as TNF-alpha in young healthy volunteers,"
said lead author Patrizio Riso in the Journal of Agricultural and Food
Chemistry (Vol. 54, pp. 2563-2566).
The placebo-controlled, double-blind crossover trial divided 26 young
healthy volunteers into two groups. Group one (N=13) was assigned to
the sequence placebo/wash-out/Lyc-o-Mato, while the second group was
assigned the inverse, Lyc-o-Mato/washout/placebo. People with kidney,
heart, and liver diseases, and pregnant women taking supplements, were
excluded from the study
The mediator for inflammation, TNF-alpha, and markers of immune
response, the cytokine IFN-gamma, were measured by blood sample
analysis. White blood cell DNA damage was also quantified.
After 26 days of either placebo or Lyc-o-Mato, the researchers found
that TNF-alpha levels were significantly decreased by 34 per cent after
consumption of the tomato drink. No changes were observed after
placebo.
The authors suggest that the effects of the tomato juice are due to one
of several mechanisms, including altering cytokine production, the
boosting of T-lymphocyte function, or the inhibition of arachidonic
acid metabolism that is catalysed by free radicals.
However, the appropriate compounds to support the latter mechanism were
not found in an analysis of the volunteers urine.
Interestingly, levels of IFN-gamma increased after the placebo drink, a
result that could not be explained by the researchers since the placebo
drink was formulated to appear and taste like the tomato drink but did
not contain any bioactive compounds. IFN-gamma levels after consuming
the tomato drink were unchanged, indicating that the tomato drink had
no effect on the immune system.
"These data add to the controversy of whether lycopene, and the other
carotenoids, affect immune response," said Riso.
DNA damage was also insignificant in both groups, a result that could
have been due to the young, healthy subjects having little DNA damage
at baseline.
These results differ somewhat from other studies that have focused on
predominantly elderly populations. Some have reported increases in
immune function, and other have reported increases in inflammation
mediators due to the tomato juice.
"Further intervention trials will follow in subjects with low
carotenoid status and/or compromised immune system," said Riso.
Israeli-company LycoRed, producers of Lyc-o-Mato, supplied the tomato
juice drink.
--------------------------------------------------------------------------------------
I wonder how much a V8 a day helps?
Any idea cruiser?
If you add those H2O2 droPs to V8 or orange juice and you only
drop TNF levels by 35% wouldn't any corresponding drop in psoriasis
be suspect? IoWs due to other factors in the diet?
randall...
Pieter
This is one I can easily try. I will try tomato/carrot juice for a
couple of weeks. Lets see what happens. Can't have any side effects.
Pieter
randall
Last post we had tomato's that can block ~35% of inflammation causing
TNF.
But does it work for P? I can hardly wait for Pieter's tests to come
in.
I found the abstract regarding he lyc-O-mata study.
Did you like a lycopene?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16569044
If so then what else is coming down the scientific boardwalk?
http://www.khou.com/news/local/houstonmetro/stories/khou060407_cd_medicalresearch.1293110a.html
Medical research studies can provide small advances or miracle cure
06:54 PM CDT on Friday, April 7, 2006
By Carolyn Campbell / 11 News
Audrey Wanger is having her blood drawn, by choice.
"Did they tell you about my veins?" she said.
Wanger is a medical research volunteer.
"Oh, you're good," she told the nurse.
KHOU-TV
Medical research serves many purposes for many people.
Wanger suffers from Raynaud's Disease. When her hands get cold, her
fingers go white, then numb.
"So I have to shake them and then the blood starts gradually refilling
back into my fingers," said Wanger.
She volunteered for one of the hundred or so medical studies being
conducted at the University of Texas, hoping to find relief.
"I heard about this study and the only treatment I knew of for this
disease was a drug that you take orally and it had some side effects,"
Wanger said.
"After we do your testing you can tell us to throw it away, or how long
we can keep it," said the nurse.
Doctors say research is the lifeblood of medicine. It's how cures are
discovered and lives are saved.
"Without these clinical research trials there would be no new drugs, no
new treatments," said Dr. Maureen Mayes, University of Texas/Memorial
Hermann Research Center.
Karolyn Bratton simply demanded to be included in Dr. Stephen Tyring's
clinical trial of a new treatment for psoriasis.
"I literally begged them to take me on. I think I'm the oldest patient
they have here," said Bratton.
Bratton has suffered from psoriasis since she was 12.
"It itches, it's embarrassing. Once you find a hairdresser, doctor you
stick with them for life because you don't want to have to explain to
anybody else that you're not dirty, you don't have a nasty disease.
It's something you inherited," Bratton said.
She's had very few outbreaks since she's been taking the experimental
drug for the past three years and she isn't even worried about side
affects.
"I would have eaten cow patties if they told me it would help my
psoriasis. I was that desperate. That's OK, I'm a guinea pig that
doesn't itch and have a crippling disease right now," Bratton said.
Desperation is one of the reasons some people volunteer for research.
But many studies also offer monetary compensation from $10 to hundreds
of dollars.
"We want to make sure it is not so high that people will overlook their
own good judgment," said Dr. Mayes.
"If the first question the person asks when they call or come in is how
much they're gonna get paid, we don't want them," said Dr. Tyring.
While medical research does provide breakthroughs, it's also a big
business, often funded by large pharmaceutical companies.
"We don't accept every clinical trial that a pharmaceutical company
offers us. We look at the ones that have the potential to be both safe
and effective.
Dr. Tyring started his own private research clinic because he wants to
do more than treat patients.
"I want to be a prevention and treatment doctor. Because I feel that
I'm just spinning my wheels if I'm just doing what I did in medical
school," said Dr. Touring.
Because of volunteers like Wanger and Bratton, research studies can
provide small advances or the next miracle cure.
"I'm one happy camper," said Bratton.
But sometimes doctors simply learn what doesn't work, and that is
progress too.
-----------------------------------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=41136
MIT Research Links Cancer, Inflammatory Disease
Main Category: Cancer/Oncology News
Article Date: 08 Apr 2006 - 4:00am (UK)
The biological processes underlying diseases such as rheumatoid
arthritis and cancer are fundamentally linked, and should be linked in
how they are treated with drugs, a series of MIT studies indicates.
Key to the work: The researchers applied an engineering approach to
cell biology, using mathematical and numerical tools normally
associated with the former discipline.
In a series of three papers, the latest of which appeared in the March
24 issue of Cell, Professors Douglas A. Lauffenburger, Peter K. Sorger
and Michael B. Yaffe, all members of MIT's Center for Cancer Research,
led a team of scientists and engineers in looking at how cells make
life-or-death decisions. Understanding what tips a cell toward survival
or death is key to treating diseases and fighting cancer through
radiation, drug therapy and chemotherapy.
The researchers looked at tumor necrosis factor (TNF), a substance
produced by the immune system that promotes cell death, and two
prosurvival hormones, epidermal growth factor (EGF) and insulin. TNF
and EGF induce conflicting prosurvival and prodeath signals, and the
"crosstalk" between these signals is not well understood. The MIT
studies provide the first big picture of how these two key factors
interact in time and space.
The studies uncovered a surprising link between inflammatory diseases
and cancer that may change how these diseases are treated in the
future.
More effective drugs
Researchers have been exploring ways to use drugs in combination to
increase their therapeutic value in fighting tumors. The results of the
three MIT studies have implications for how two classes of drugs
involving TNF and EGF affect common biological processes in the body.
Drugs that inhibit TNF are used to treat debilitating chronic
inflammatory diseases such as rheumatoid arthritis. Yet TNF, which
causes inflammation, also leads to generation of the EGF signals that
play a role in many cancers. (The breast cancer drug Herceptin, for
example, works by blocking EGF-induced signals.) "TNF is supposed to
kill cells. It's counterintuitive that it simultaneously promotes cell
survival by sending an 'autocrine' EGF signal to itself," said Sorger,
a professor of biology and head of MIT's Center for Cell Decision
Processes. Autocrine EGF messages are analogous to mailing yourself a
letter. In the case of TNF, cells also mail back the response via
another hormone, IL-1.
"With what we now understand about the interactions between these two
factors, we should aim for increasing the therapeutic value from these
drugs," Sorger said. "There is a fundamental molecular connection
between diseases such as rheumatoid arthritis and cancer. Their protein
cascades are connected; one stimulates the process of the other."
"In drug development, we want to identify the really important hubs in
the network we should be targeting and when we should be targeting
them," said Yaffe, an associate professor of biology and biological
engineering. "It's key to figure out the most critical point in the
cell cycle for the drug to intervene. This work will help accomplish
that goal."
Protein wars
Among the cells lining the intestines of a person with inflammatory
bowel disease, two different camps are at war. TNF launches an attack,
killing many of the epithelial surface cells, while EGF struggles to
keep the cells alive and dividing to repair the damage.
In every cell, genes create proteins, the building blocks of life.
Besides carrying out the functions of keeping the cell alive, some
proteins such as TNF and EGF work as signals, turning on or off other
genes. In a cascade effect, the proteins from these genes may affect
still more genes. What's more, a single protein behaves differently at
different points in time: A protein may do one thing early after
stimulation and something else later on.
Researchers want to be able to predict how cells will respond to tiny
molecular changes that spur them to develop, multiply or die. If
researchers knew exactly how much of a certain protein was needed to
kill a cancer cell and exactly when in the cell's life cycle it would
be most lethal, drugs could be custom-designed to destroy malignant
cells while leaving normal cells intact, Yaffe said.
But for many cell-decision networks, there is simply not enough
information about the signaling proteins and reactions to construct a
believable model that would allow accurate predictions to be made. Can
you design an effective model without measuring every one of the tens
of thousands of proteins in a cell?
Hidden connections
"There are a lot of variables and a limited set of observations,"
Lauffenburger said of cell biology. "How can you abstract what's going
on underneath the surface? We're never going to have complete
knowledge, but the question was, could we construct a model that admits
that we don't know everything, but we know enough to do something
useful?" Lauffenburger is head of MIT's Biological Engineering Division
and is the Whitaker Professor of Bioengineering.
To answer that question, the team used an engineering approach
typically applied to manufacturing or software. "At some point, we need
to bring new tools to bear on complexity, and those new tools are
engineering-based mathematical and numerical tools," Sorger said. "Just
as we can engineer extremely complicated systems like jets that we
can't understand in their totality just by looking at them, we can do
the same thing in biology." Modeling signaling pathways with computers
is one of the tactics of MIT's Center for Cell Decision Processes.
"Models store our aggregate biological knowledge in a tractable way and
are used to identify which proteins and pathways are most critical for
mediating cell responses," Yaffe said. The research team plugged
measurements of thousands of signaling proteins gathered in painstaking
laboratory experiments into the models, providing a "firm theoretical
grounding" to intuit how protein network interactions affect cell
behavior, Yaffe said.
Yaffe divided cell signals into two major dimensions that can be
plotted on a graph with a stress/death axis and a survival/growth axis.
Where the conflicting factors fall on the graph determines whether the
cell upon which they are acting lives or dies. "Our study gives us a
broader functional sampling of a lot of things at the same time," he
said.
Using this new approach involves teams of researchers, a concept
unusual in traditional cell biology. Working as a team, computational
scientists remain in close touch with their laboratory-based
collaborators. Interdisciplinary scientists working at the interface of
biology and computation is the way of the future, according to Kevin A.
Janes, graduate student in biological engineering and one of the
study's co-authors.
The payoff is high. Combining broad protein-based measurements and
computation revealed the big picture, uncovering connections between
spheres of biology previously believed to be distinct. "We are finding
that things that once appeared to be biologically independent are
closely connected," Sorger said. "We are not just collections of
independent parts."
------------------------------------------------------------
http://www.baltimoresun.com/news/health/bal-hs.foreman07apr07,0,3989763.story?coll=bal-health-headlines
Chronic inflammation may be connected to medical maladies
Judy Foreman -- Medical Matters
Originally published April 7, 2006
The idea is as simple as it is radical: Chronic inflammation, spurred
by an immune system run amok, appears to play a role in medical evils
from arthritis to Alzheimer's, from diabetes to heart disease.
Advertisement
There's no grand proof of this "theory of everything." But doctors say
it's compelling enough that we should act as if it were true -- which
means eating an "anti-inflammatory diet," doing lots of physical
activity, and losing the dangerous, internal belly fat that pumps out
the chemicals that drive inflammation (more on this nasty chemistry
later).
Inflammation, of course, is not all bad. In fact, because it's part of
the typical immune response, it's essential for battling germs and
healing wounds. The familiar redness, heat, swelling and pain that come
from, say, a hangnail or a splinter are signs of inflammation at work.
It's when the inflammation process fails to shut off after an infection
or injury is over that trouble sets in. Persistent, low-level
inflammation may set the stage for the chronic diseases of later life,
many doctors now believe.
Over the evolutionary eons, "we developed these important host defenses
to let us get to reproductive age," said Dr. Peter Libby, chief of
cardiovascular medicine at Boston's Brigham and Women's Hospital. "Now,
the life span has almost doubled, and these same [immune responses]
contribute to diseases in the end."
Chronic inflammation is so similar in different diseases, Libby said,
that when he lectures, he uses many of the same slides, whether he's
talking about diseases of the heart, kidneys, joints, lung or other
tissues.
Only a few years ago, heart attacks were explained as a plumbing
problem -- blood vessels that became clogged with atherosclerotic
plaque as "bad" (LDL) cholesterol was deposited on vessel walls.
Now doctors know that this bad cholesterol becomes embedded inside
artery walls as well, where the immune system "sees" it as an invader
to be attacked. The inflammation in arteries, essentially a revved-up
immune response, can damage arteries and cause "vulnerable" plaque to
burst.
It is because inflammation is seen as such a hallmark of heart disease
that many doctors use a test for inflammation called CRP to help assess
a person's cardiac risk.
Diabetes connection
It's long been known that type 1 diabetes is linked to inflammation --
the body's immune system attacks the cells that make insulin. New
research is suggesting that type 2 diabetes, the kind that generally
sets in during adulthood, often begins with insulin resistance, in
which cells stop responding properly to insulin. Doctors now know that
during chronic inflammation, one of the chemicals released is TNF, or
tumor necrosis factor, which makes cells more resistant to insulin.
"No one would have thought these things were related," but they are,
said Dr. Walter Willett, chairman of the department of nutrition at the
Harvard School of Public Health.
The TNF connection also helps explain why obesity, particularly
abdominal obesity, leads to diabetes. "Fat cells used to be thought of
as storage depots for energy, as metabolically inactive," Libby said.
"Now we know that fat cells are little hotbeds of inflammation --
excess fat in the belly is a great source of inflammation."
Autoimmune diseases such as rheumatoid arthritis are also believed to
be linked to inflammation. In arthritis, for instance, inflammatory
cells called cytokines lead to the production of enzymes that break
down cartilage in joints.
Inflammation also plays some role in Alzheimer's disease, said Linda
Van Eldik, a neurobiologist at the Northwestern University Feinberg
School of Medicine.
Whenever the brain is injured or infected, cells in the brain called
glia pump out cytokines. Normally, this response shuts down when the
injury or infection is over.
"But in chronic neurodegenerative diseases like Alzheimer's, these
glial cells are activated too high or too long or both," Van Eldik
said. The plaques and tangles in patients' brains attract the attention
of glial cells, making them pump out even more cytokines to try to
repair this damage, creating chronic inflammation.
Even cancer may have some inflammatory triggers, though the links are
less well worked out, said Dr. David Heber, director of the University
of California, Los Angeles Center for Human Nutrition. Among its other
tricks, inflammation promotes the release of free radicals, dangerous
forms of oxygen that can damage DNA. At chronic, low doses, Heber said,
"free radicals can stimulate tumors to grow."
There are other chemical overlaps between inflammation and cancer too,
said Dr. Robert Tepper, president of research and development for
Millennium Pharmaceuticals in Cambridge, Mass. The same
protein-signaling molecules called chemokines that tell white blood
cells when to flock to an injury or infection also tell cancer cells
when and where to spread, suggesting a link between cancer spread and
the inflammatory response.
Cut your risk
That's the bad news. Now, the good: There's a lot you can do to reduce
the risks of chronic inflammation. First and foremost is to lose weight
if you are chubby, especially around the middle. It's visceral fat that
pumps out the lion's share of pro-inflammatory cytokines. Exercise, of
course, is the way to do it -- anything that gets you moving and burns
calories will help.
And diet is crucial. "Some types of food we eat can cause inflammation
and others can decrease it," said Lisa Davis, a nutritionist at the
Center for Human Nutrition at the Johns Hopkins School of Public
Health. On the good side, the Mediterranean diet, which is rich in
fruits, vegetables, fish and olive oil, was shown in a randomized study
in 2004 to be linked to reductions in weight, C-reactive protein and
insulin resistance.
You can eat fats, but eat the right kind, such as olive oil, and
include those rich in omega-3 fatty acids, such as that found in
salmon, tuna, walnuts, soy and flax seed oil.
Finally, you can also consider statin drugs, which lower cholesterol
and may reduce the inflammation associated with heart disease. Also
consider taking a baby aspirin a day, though you should check with your
doctor first. Ditto for NSAIDS -- over-the-counter non-steroidal
anti-inflammatory drugs -- which reduce inflammation but cause bleeding
and other side effects.
Reducing the inflammation in your life won't guarantee you will live
forever, but it's a step in the right direction
-----------------------------------------------------------------------------------------------------
randall... to bad an aspirin a day doesn't do it for P!
randall
If it works for MS, will it work for P?
http://www.docguide.com/news/content.nsf/news/852571020057CCF68525714C004DB2D2
The Immune Response Corporation's NeuroVax Restores FOXP3+ T-Cell
Levels Believed to Help in Multiple Sclerosis
Oral Presentation at American Academy of Neurology
CARLSBAD, C.A. -- April 10, 2006 -- The Immune Response Corporation
(OTCBB:IMNR.OB) announced that its T-cell receptor peptide vaccine
candidate, NeuroVax™, induces increased FOXP3 expression resulting in
re-establishment of normal levels of the FOXP3+ regulatory T-cells
believed to be important in controlling the development of multiple
sclerosis (MS).
Results of the recently completed open-label trial in MS patients were
presented yesterday by Dr. Dennis Bourdette, Oregon Health and Sciences
University (OHSU) Department of Neurology Chair, during an oral
presentation at the 58th Annual Meeting of the American Academy of
Neurology in San Diego, CA.
"NeuroVax™ is a promising candidate for development as a novel
vaccine for treating patients with MS," said Dr. Bourdette, who is also
a member of the Company's Scientific Advisory Board guiding the
development of NeuroVax™. "The TCR peptide vaccine works by
down-regulating the pathogenic T-cells causing the MS. Our clinical
findings indicate that NeuroVax™ induces strong, disease-specific
immune responses in essentially all the MS patients treated. The
findings indicate that an important part of the strong disease-specific
immune response induced by NeuroVax™ is the stimulation of FOXP3+
regulatory T-cells. This exciting approach could play an important role
in the treatment of MS."
About the Study
This one-year open-label trial enrolled 25 patients who received
monthly injections of NeuroVax™. Seventeen of these were
newly-enrolled patients, and showed statistically lower baseline levels
of FOXP3+ mRNA measured by RT-PCR (P =.03) and FOXP3 protein expression
by Western blot (p=.02) when compared with healthy controls.
Following immunization of these MS patients with NeuroVax™, 14/17
patients at 52 weeks demonstrated increased FOXP3+ mRNA expression over
baseline (P =.01) and FOXP3 protein expression as a group was also
statistically increased over baseline (P =.02). In a number of
patients, FOXP3 message and protein expression became higher than those
in healthy controls.
These data indicate that a key portion of the strong immune responses
induced in patients given NeuroVax™ include increases in expression
of FOXP3, a marker which is associated with the activity of CD4+CD25+
regulatory T-cells. NeuroVax™ thus may be boosting an important
immune regulatory network which may be clinically beneficial for MS
patients.
"These exciting findings on the regulatory mechanism of how NeuroVax™
can be influencing the pathogenic T-cells causing MS, coupled with our
earlier MRI data that suggest NeuroVax™ may decrease the number of
total new Gadolinium enhancing lesions, are the basis for the design of
a 300-patient Phase II study that will be initiated later this year in
Eastern Europe and the United States that will test the clinical
benefit of NeuroVax™ by assessing its effect on MRI and relapse
rates," commented Dr. Joseph O'Neill, President and Chief Executive
Officer of The Immune Response Corporation.
About Multiple Sclerosis
MS is an autoimmune disease in which the immune system mistakenly
attacks normal tissues of the central nervous system. It afflicts
approximately 400,000 people in the United States and more than 2.5
million worldwide (source: National MS Society).
The disease is caused by activation of a specific subset of the
patient's own white blood cells, pathogenic T-cells, which then attack
a fatty tissue called myelin that surrounds and protects nerve fibers
and creates scarring (sclerosis) that interferes with the normal
transmission of nerve impulses. This damage, in turn, leads to a
variety of chronic and highly individual and unpredictable neurological
symptoms, ranging from movement and balance problems to vision
impairment.
Autoimmune diseases such as MS may result from the failure of normal
immune regulatory mechanisms to prevent proliferation of pathogenic
T-cells. Specifically, The Immune Response Corporation's research
indicates that MS patients have diminished levels of FOXP3 message and
protein expression levels in peripheral T-cells. This observation is
the first to link a defect in functional peripheral immunoregulation to
an established genetic marker, FOXP3, which previously has been shown
to be involved in maintaining immune tolerance and repressing the
development of autoimmune diseases such as MS.
About The Immune Response Corporation
The Immune Response Corporation (OTCBB: IMNR.OB) is an
immuno-pharmaceutical company focused on developing products to treat
autoimmune and infectious diseases. The Company's lead immune-based
therapeutic product candidates are NeuroVax™ for the treatment of MS
and IR103 for the treatment of HIV infection. Both of these therapies
are in Phase II clinical development and are designed to stimulate
pathogen-specific immune responses aimed at slowing or halting the rate
of disease progression.
NeuroVax™, which is based on the Company's patented T-cell receptor
(TCR) peptide technology, has shown potential clinical value in the
treatment of relapsing forms of MS. NeuroVax™ has been shown to
stimulate strong, disease-specific cell-mediated immunity in nearly all
patients treated and appears to work by enhancing levels of FOXP3+ Treg
cells that are able to down-regulate the activity of pathogenic T-cells
that cause MS.
Increasing scientific findings have associated diminished levels of
FOXP3+ Treg cell responses with the pathogenesis and progression of MS
and other autoimmune diseases such as rheumatoid arthritis (RA),
psoriasis and Crohn's disease.
NeuroVax™ is in clinical development by The Immune Response
Corporation and is not approved by any regulatory agencies in any
country at this time.
NeuroVax™ is a trademark of The Immune Response Corporation
----------------------------------------------------------------------------------
Lets check these suspects,
http://groups.google.com/groups/search?q=FOXP3%2B+psoriasis&qt_s=Search
&
A well adapted regulatory contrivance: regulatory T cell development
and the forkhead family transcription factor Foxp3
http://www.nature.com/ni/journal/v6/n4/fig_tab/ni1179_F2.html
[...]
Figure 2. Models of dominant tolerance.
(a) Dedicated Treg cell lineage. In this model, Treg cell lineage
commitment through induction of Foxp3 expression occurs preferentially
in thymocytes and recent thymic emigrants, whereas induction of
Foxp3-expression in mature peripheral nonregulatory T cells in both
humans and mice in physiological conditions is a rare and relatively
inefficient process. Activation of effector T cells results in
production of IL-2, which expands the Treg cell population during
immune activation. Treg cells function mainly to control T cell
self-reactivity and autoimmune inflammation. As a consequence of this
function, Treg cells cause downmodulation of inflammation associated
with pathogen-specific immune responses while not specifically
developing to limit these responses. (b) Adaptive Treg cell effectors.
In this model, Treg cells are generated both in the thymus and de novo
from effector nonregulatory T cells as a consequence of immune
activation. The signals inducing Foxp3 expression in peripheral T cells
in vivo have yet to be clearly defined. Here, Foxp3 induction in
effector nonregulatory cells acts as a form of negative feedback to
directly regulate conventional antigen-specific immune responses. One
prediction of this model is the generation of pathogen-specific
Foxp3-expressing Treg cells during the course of an ongoing infection.
In this model, Foxp3 functions not as a Treg cell lineage specification
factor but as a transcriptional regulator of an immunosuppressive
effector program.
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=50943
[...]
10. FOXP3 is a crucial regulatory gene for the development and function
of CD25(+)CD4(+) regulatory T cells <sniP>
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15466453
Crucial role of FOXP3 in the development and function of human
CD25+CD4+ regulatory T cells.
Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S, Maeda M,
Onodera M, Uchiyama T, Fujii S, Sakaguchi S.
Department of Experimental Pathology, Institute for Frontier Medical
Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto
606-8507, Japan.
Naturally occurring CD25(+)CD4(+) regulatory T cells are engaged in the
maintenance of immunological self-tolerance and down-regulation of
various immune responses. Recent studies with mice showed that Foxp3,
which encodes the transcription factor Scurfin, is a master regulatory
gene for the development and function of CD25(+)CD4(+) regulatory T
cells. Here we examined the role of FOXP3 in human CD25(+)CD4(+)
regulatory T cells. The FOXP3 gene and its protein product were
preferentially expressed in peripheral CD25(+)CD4(+) T cells, in
particular CD25(+)CD45RO(+)CD4(+) T cells in normal individuals and,
interestingly, in some human T cell leukemia virus type 1-infected T
cell lines, which constitutively express CD25. TCR stimulation of
CD25(-)CD45RO(-)CD4(+) naive T cells failed to elicit FOXP3 expression
at the gene or protein level. Ex vivo retroviral gene transfer of
FOXP3, on the other hand, converted peripheral CD25(-)CD45RO(-)CD4(+)
naive T cells into a regulatory T cell phenotype similar to
CD25(+)CD4(+) regulatory T cells. For example, FOXP3-transduced T cells
exhibited impaired proliferation and production of cytokines including
IL-2 and IL-10 upon TCR stimulation, up-regulated the expression of
regulatory T cell-associated molecules such as CD25 and CTL-associated
antigen-4 and suppressed in vitro proliferation of other T cells in a
cell-cell contact-dependent manner. Thus, human FOXP3 is a crucial
regulatory gene for the development and function of CD25(+)CD4(+)
regulatory T cells, and can be used as their reliable marker.
Furthermore, regulatory T cells de novo produced from normal naive T
cells by FOXP3 transduction can be instrumental for treatment of
autoimmune/inflammatory diseases and negative control of various immune
responses.
PMID: 15466453
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16387603
Absence of T-regulatory cell expression and function in atopic
dermatitis skin.
Verhagen J, Akdis M, Traidl-Hoffmann C, Schmid-Grendelmeier P, Hijnen
D, Knol EF, Behrendt H, Blaser K, Akdis CA.
Swiss Institute of Allergy and Asthma Research, Davos Platz,
Switzerland.
BACKGROUND: The role of regulatory T cells has been widely reported in
the suppression of T-cell activation. A dysfunction in CD4(+)CD25(+)
T-regulatory cell-specific transcription factor FoxP3 leads to immune
dysregulation, polyendocrinopathy, enteropathy X-linked syndrome, often
associated with atopic dermatitis. Increasing the number and activity
of regulatory T cells in affected organs has been suggested as a remedy
in various inflammatory diseases, including allergy. OBJECTIVE: To
determine the presence and function of regulatory T cells in atopic
dermatitis. METHODS: Immunohistochemistry of lesional atopic dermatitis
skin and control skin conditions was used to demonstrate regulatory
cells and cytokines in situ. The role of effector and regulatory T
cells as well as their specific cytokines in apoptosis in human
keratinocyte cultures and artificial skin equivalents was investigated.
RESULTS: Human T-regulatory type 1 cells, their suppressive cytokines,
IL-10 and TGF-beta, as well as receptors for these cytokines were
significantly expressed, whereas CD4(+)CD25(+)FoxP3(+) T-regulatory
cells were not found in lesional and atopy patch test atopic dermatitis
or psoriasis skin. Both subsets of regulatory T cells suppress the
allergen-specific activation of T(H)1 and T(H)2 cells. In coculture and
artificial skin equivalent experiments, subsets of T-regulatory cells
neither induced keratinocyte death nor suppressed apoptosis induced by
skin T cells, T(H)1 cells, IFN-gamma, or TNF-alpha. CONCLUSION: A
dysregulation of disease-causing effector T cells is observed in atopic
dermatitis lesions, in association with an impaired
CD4(+)CD25(+)FoxP3(+) T-cell infiltration, despite the expression of
type 1 regulatory cells in the dermis.
PMID: 16387603
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16030186
Expression of the inhibitory receptor ILT3 on dendritic cells is
dispensable for induction of CD4+Foxp3+ regulatory T cells by
1,25-dihydroxyvitamin D3.
Penna G, Roncari A, Amuchastegui S, Daniel KC, Berti E, Colonna M,
Adorini L.
BioXell, Milano, Italy.
1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is a secosteroid hormone
that renders dendritic cells (DCs) tolerogenic, favoring the induction
of regulatory T cells. Induction of DCs with tolerogenic properties by
1,25(OH)(2)D(3) is associated with increased selective expression of
immunoglobulin-like transcript 3 (ILT3), suggesting its involvement in
the immunoregulatory properties of this hormone. Here we show an in
vivo correlate of the increased ILT3 expression on DCs in healing
psoriatic lesions following topical treatment with the 1,25(OH)(2)D(3)
analog calcipotriol. Analysis of DC subsets reveals a differential
regulation of ILT3 expression by 1,25(OH)(2)D(3), with a marked
up-regulation in myeloid DCs but no effect on its expression by
plasmacytoid DCs. A regulatory role for ILT3 expressed on DCs is
indicated by the increased interferon-gamma (IFN-gamma) secretion
promoted by anti-ILT3 addition to cultures of DCs and T cells, but this
effect is blunted in 1,25(OH)(2)D(3)-treated DCs, suggesting
ILT3-independent mechanisms able to regulate T-cell activation.
Although ILT3 expression by DCs is required for induction of regulatory
T cells, DC pretreatment with 1,25(OH)(2)D(3) leads to induction of
CD4(+)Foxp3(+) cells with suppressive activity irrespective of the
presence of neutralizing anti-ILT3 monoclonal antibody (mAb),
indicating that ILT3 expression is dispensable for the capacity of
1,25(OH)(2)D(3)-treated DCs to induce regulatory T cells.
PMID: 16030186
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15611238
Dysfunctional blood and target tissue CD4+CD25high regulatory T cells
in psoriasis: mechanism underlying unrestrained pathogenic effector T
cell proliferation.
Sugiyama H, Gyulai R, Toichi E, Garaczi E, Shimada S, Stevens SR,
McCormick TS, Cooper KD.
Department of Dermatology, University Hospitals of Cleveland and Case
Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106,
USA.
The balance between regulatory and effector functions is important for
maintaining efficient immune responses, while avoiding autoimmunity.
The inflammatory skin disease psoriasis is sustained by the ongoing
activation of pathogenic effector T cells. We found that a CD4(+) T
lymphocyte subpopulation in peripheral blood, phenotypically
CD25(high), CTLA-4(+), Foxp3(high) (regulatory T (Treg) cells), is
deficient in its suppressor activity in psoriasis. This was associated
with accelerated proliferation of CD4(+) responder T cells in
psoriasis, the majority of which expressed CXCR3. Nevertheless,
criss-cross experiments isolated the defect to psoriatic Treg cells. To
examine Treg cells in a nonlymphoid tissue of a human T cell-mediated
disease, Treg cells were also analyzed and isolated from the site of
inflammation, psoriatic lesional skin. At the regulatory vs effector T
cells ratios calculated to be present in skin, however, the psoriatic
Treg cell population demonstrated decreased suppression of effector T
cells. Thus, dysfunctional blood and target tissue CD4(+)CD25(high)
Treg cell activity may lead to reduced restraint and consequent
hyperproliferation of psoriatic pathogenic T cells in vivo. These
findings represent a critical component of human organ-specific
autoimmune disease and may have important implications with regard to
the possible therapeutic manipulation of Treg cells in vivo.
PMID: 15611238
Let's see if LPS figures in here with foxP3,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16180249
Autoreactive human peripheral blood CD8+ T cells with a regulatory
phenotype and function.
Jarvis LB, Matyszak MK, Duggleby RC, Goodall JC, Hall FC, Gaston JS.
University of Cambridge Clinical School, Dept. of Medicine,
Addenbrooke's Hospital, Cambridge, UK.
Despite substantial advances in our understanding of CD4+ CD25+
regulatory T cells, a possible equivalent regulatory subset within the
CD8+ T cell population has received less attention. We now describe
novel human CD8+/TCR alphabeta+ T cells that have a regulatory
phenotype and function. We expanded and cloned these cells using
autologous LPS-activated dendritic cells. The clones were not
cytolytic, but responded in an autoreactive HLA class I-restricted
fashion, by proliferation and production of IL-4, IL-5, IL-13 and
TGFbeta1, but not IFN-gamma. They constitutively expressed CD69 and
CD25 as well as molecules associated with CD4+ CD25+ regulatory T
cells, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)
and Foxp3. They suppressed IFN-gamma production and proliferation by
CD4+ T cells in vitro in a cell contact-dependent manner, which could
be blocked using a CTLA-4-specific mAb. They were more readily isolated
from patients with ankylosing spondylitis and may therefore be
up-regulated in response to inflammation. We suggest that they are the
CD8+ counterparts of CD4+ CD25+ regulatory T cells. They resemble
recently described CD8+ regulatory cells in the rat that were able to
abrogate graft-versus-host disease. Likewise, human HLA-restricted CD8+
regulatory T cells that can be cloned and expanded in vitro may have
therapeutic applications.
PMID: 16180249
Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by
dendritic cells.
Fehervari Z, Sakaguchi S.
Department of Experimental Pathology, Institute for Frontier Medical
Sciences, Kyoto University, Shogo-in 53, Sakyo-ku, Kyoto 606-8507,
Japan. ze...@frontier.kyoto-u.ac.jp
Naturally occurring CD4+CD25+ regulatory T (TR) cells play crucial
roles in normal immunohomeostasis. CD4+CD25+ TR cells exhibit a number
of interesting in vitro properties including a 'default state' of
profound anergy refractory to conventional T cell stimuli. We
investigated the in vitro activation requirements of CD4+CD25+ TR cells
using bone marrow-derived DC, which as professional antigen presenting
cells (APC) can support the activation of normal naive T cells.
Comparison of different APC types revealed that LPS-matured DC were by
far the most effective at breaking CD4+CD25+ TR cell anergy and
triggering proliferation, and importantly their IL-2 production.
Examination of Foxp3, a key control gene for CD4+CD25+ TR cells, showed
this to be stably expressed even during active proliferation. Although
CD4+CD25+ TR cell proliferation was equivalent to that of CD25- cells
their IL-2 production was considerably less. Use of IL-2-/- mice
demonstrated that the DC stimulatory ability was not dependent on IL-2
production; nor did IL-15 appear crucial but was, at least in part,
related to costimulation. DC also blocked normal CD4+CD25+ TR
cell-mediated suppression partially via IL-6 secretion. DC therefore
possess novel mechanisms to control the suppressive ability, expansion
and/or differentiation of CD4+CD25+ TR cells in vivo.
PMID: 15520045
& finally
Lipopolysaccharide induces CD25-positive, IL-10-producing lymphocytes
without secretion of proinflammatory cytokines in the human colon: low
MD-2 mRNA expression in colonic macrophages.
Shirai Y, Hashimoto M, Kato R, Kawamura YI, Kirikae T, Yano H,
Takashima J, Kirihara Y, Saito Y, Fujino MA, Dohi T.
Department of Gastroenterology, Research Institute, International
Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655,
Japan.
Despite the huge number of colonized Gram-negative bacteria in the
colon, the normal colon maintains its homeostasis without any excessive
immune response. To investigate the potential mechanisms involved,
human colonic lamina propria mononuclear cells (LPMCs) obtained from
uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared
from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as
representatives of indigenous flora, or pathogenic Salmonella minnesota
(SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in
response to any type of LPS. Colonic macrophages barely expressed mRNA
for MD-2, an essential association molecule for LPS signaling via
Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression
in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the
low expression of functioning LPS receptor molecules and induction of
IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a
central role in the maintenance of colonic immunological homeostasis.
PMID: 14997033
It comes back to the gut again. The lower Gi tract for P isn't
homeostatic for TREGS?
randall... the dregs, er tregs of our P inflammations and/or genes?
randall
Healing Honey: The Sweet Evidence Revealed
http://www.sciencedaily.com/releases/2006/04/060407151107.htm
But is it a honey of a deal for P?
For the whole story,
http://ijl.sagepub.com/current.dtl
http://ijl.sagepub.com/cgi/reprint/5/1/6
I suPPose this could be used as a type of occlusion in
cruiser's oxygen/niacin/+supplements trial.
You would have the honey healing effects + occlusion,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8930477
Then again it would be sweet should it work. Or not?
**************************************************
I'm intending to send this next abstract off to Mikhail for his
perspective on it.
His Group B strep/gut theory as the cause of P is still on the table
isn't it?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16603837
Skin basement membrane zone: a depository for circulating microbial
antigen evoking psoriasis and autoimmunity.
Noah PW, Handorf CR, Skinner RB Jr, Mandrell TD, Rosenberg EW.
Departments of Medicine (Dermatology) and Preventive Medicine,
University of Tennessee, Memphis, TN 38104-7514.
Background. Elevated levels of antibody to streptococcal exoenzymes
have been found in patients with psoriasis or psoriatic arthritis.
Research on the role of streptococcal antigen in psoriasis has been
hampered by a potential molecular mimicry between streptococcal
epitopes and human epidermal keratin. Objective and Methods. Evidence
of microbial product was sought in skin biopsies of psoriasis patients
thought clinically to have either streptococcal carrier state or
gastrointestinal candidal colonization. A polyclonal antibody to
streptococcal-derived exoenzymes unlikely to share antigenic structures
with normal human skin, and an anticandidal antibody, were used with
linked streptavidin biotin amplification stain. Results. The predicted
microbial product appeared heavily in lesional epidermis, but
unexpectedly also as a thin deposit along the skin basement membrane
zone (SBMZ) of apparently unaffected skin. Staining was negative for
nonpsoriatic subjects. Conclusions. The findings support a direct
effect of microbial antigen in psoriasis. They also suggest an
important role for SBMZ as a very large adhesive surface in the first
step of a process of percutaneous epidermal elimination of foreign
antigens and microbial toxins. The many autoimmune phenomena seen so
often at the SBMZ are probably a physiologic part of this important
immune function. Efforts to enhance the adhesive properties of SBMZ
should be exploitable for both diagnostic and therapeutic benefit.
PMID: 16603837
OK, its been a long time since i posted any LAB (lacti acid bacteria)
posts.
Is the small and not the large intestine, the battleground for tackling
P?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16148174
Role of intestinal epithelial cells in immune effects mediated by
gram-positive probiotic bacteria: involvement of toll-like receptors.
Vinderola G, Matar C, Perdigon G.
Department de Chimie et Biochemie, Universite de Moncton (NB) E1A 3E9,
Canada.
The mechanisms by which probiotic bacteria exert their effects on the
immune system are not completely understood, but the epithelium may be
a crucial player in the orchestration of the effects induced. In a
previous work, we observed that some orally administered strains of
lactic acid bacteria (LAB) increased the number of immunoglobulin A
(IgA)-producing cells in the small intestine without a concomitant
increase in the CD4(+) T-cell population, indicating that some LAB
strains induce clonal expansion only of B cells triggered to produce
IgA. The present work aimed to study the cytokines induced by the
interaction of probiotic LAB with murine intestinal epithelial cells
(IEC) in healthy animals. We focused our investigation mainly on the
secretion of interleukin 6 (IL-6) necessary for the clonal expansion of
B cells previously observed with probiotic bacteria. The role of
Toll-like receptors (TLRs) in such interaction was also addressed. The
cytokines released by primary cultures of IEC in animals fed with
Lactobacillus casei CRL 431 or Lactobacillus helveticus R389 were
determined. Cytokines were also determined in the supernatants of
primary cultures of IEC of unfed animals challenged with different
concentrations of viable or nonviable lactobacilli and Escherichia
coli, previously blocked or not with anti-TLR2 and anti-TLR4. We
concluded that the small intestine is the place where a major
distinction would occur between probiotic LAB and pathogens. This
distinction comprises the type of cytokines released and the magnitude
of the response, cutting across the line that separates IL-6 necessary
for B-cell differentiation, which was the case with probiotic
lactobacilli, from inflammatory levels of IL-6 for pathogens.
PMID: 16148174
Diversity, vitality and activities of intestinal lactic acid bacteria
and bifidobacteria assessed by molecular approaches.
Vaughan EE, Heilig HG, Ben-Amor K, de Vos WM.
Wageningen University, Laboratory of Microbiology, Hesselink van
Suchtelenweg 4, CT 6703, Wageningen, The Netherlands.
elaine....@unilever.com
While lactic acid bacteria and bifidobacteria have been scientifically
important for over a century, many of these are marketed today as
probiotics and have become a valuable and rapidly expanding sector of
the food market that is leading functional foods in many countries. The
human gastro-intestinal tract with its various compartments and complex
microbiota is the primary target of most of these functional foods
containing lactic acid bacteria and bifidobacteria (LAB&B). In
addition, their use as vectors for delivery of molecules with
therapeutic value to the host via the intestinal tract is being
studied. This review focuses on molecular approaches for the
investigation of the diversity of lactic acid bacteria and
bifidobacteria in the human intestine, as well as tracking of probiotic
bacteria within this complex ecosystem. Moreover, methodologies to
determine the viability of the lactic acid bacteria and bifidobacteria
and molecular approaches to study the mechanisms by which they adapt,
establish and interact with the human host via the digestive tract, are
described.
PMID: 16125009
Kids with eczema have varied bugs in the gut.
Distinct Pattern of Commensal Gut Microbiota in Toddlers with Eczema.
Mah KW, Bjorksten B, Lee BW, van Bever HP, Shek LP, Tan TN, Lee YK,
Chua KY.
Department of Pediatrics, Yong Loo Lin School of Medicine, National
University of Singapore, Singapore.
Background: Recent studies have demonstrated differences in the
composition of gut microbiota in infants with and without allergic
diseases, particularly eczema. Methods: A case-control study involving
21 toddlers (age 3.0 +/- 0.5 years) with and 28 age-matched toddlers
without eczema was conducted. Four groups of aerobic gut microbiota
were identified and quantitated in stool samples grown on selective
media. Three groups of anaerobes were enumerated by fluorescent in situ
hybridization followed by quantitative flow cytometry. We also
performed molecular typing of lactic-acid-producing bacteria (LAB) and
enterococcal isolates to facilitate detailed analysis at species level
by bacterial 16S rDNA sequencing. Results: Toddlers with eczema
harbored significantly lower counts of Bifidobacterium [(median 0.14
(25th and 75th percentile: 0.04 and 0.47) vs. 0.71% (0.16, 1.79) of
cells acquired, p = 0.003)] and Clostridium [(0.28 (0.09, 0.78) vs.
0.83% (0.35, 1.82) of cells acquired, p = 0.012)] but significantly
higher counts of total LAB [7.3 (6.1, 8.5) vs. 5.7 (4.4, 7.3) log
CFU/g, p = 0.006] in particular enterococci [6.3 (4.8, 7.4) vs. 5.0
(3.4, 6.4) log CFU/g, p = 0.018]. There was no significant correlation
between eczema severity score and bifidobacterial counts. Conclusion:
The results further confirm previous reports that the gut
microecosystem differs between children with and without eczema and
extend them beyond infancy. Copyright (c) 2006 S. Karger AG, Basel.
PMID: 16601353
Recommendations for improved use of the murine TNBS-induced colitis
model in evaluating anti-inflammatory properties of lactic acid
bacteria: technical and microbiological aspects.
Foligne B, Nutten S, Steidler L, Dennin V, Goudercourt D, Mercenier A,
Pot B.
Bacteriologie des Ecosystemes, Institut Pasteur de Lille, Lille,
France.
Probiotic bacteria have been shown to exert promising beneficial
effects in different types of intestinal disorders, including chronic
inflammation. In this context, animal models of inflammatory bowel
disease are useful in studying the possible prophylactic role of
candidate probiotic strains. This study aimed at evaluating the
critical technological and microbiological parameters as well as the
robustness of the murine trinitrobenzene sulfonic acid (TNBS)-induced
model of colitis, after intragastric administration of lactic acid
bacteria (LAB) preparations. A standardized methodology was applied to
assess the protective effect achieved by various bacterial
concentrations and culture conditions of the reference strain
Lactobacillus plantarum NCIMB 8826. Not only was protection found to
vary in function in different levels of colitis, but also repeated
experiments showed a clear bacterial dose-dependent attenuation of
colitis. The physiological stage of bacteria was shown to impact as
well, with substantial, mild, or reduced improvement of inflammatory
scores for exponentially growing, stationary-phase, or killed bacteria,
respectively. A recombinant strain, secreting murine interleukin-10
(IL-10) and previously reported to successfully treat colitis in two
different models of murine colitis (dextran sulfate sodium [DSS] and
IL-10-deficient mice), was used to validate the final experimental
conditions. In conclusion, we identified and optimized some of the key
parameters that need to be controlled in order to ensure reliable
comparison of results generated over a long period of time or
independent experiments. The recommendations for an improved model
presented here will prove to be helpful for reproducible, independent
comparison of the anti-inflammatory potential of wild-type or
recombinant candidate probiotic strains, whether administered as pure
cultures or as blends.
PMID: 16534687
Structure-function relationships of glucansucrase and fructansucrase
enzymes from lactic acid bacteria.
van Hijum SA, Kralj S, Ozimek LK, Dijkhuizen L, van Geel-Schutten IG.
Department of Molecular Genetics, Groningen Biomolecular Sciences and
Biotechnology Institute, University of Groningen, P.O. Box 14, 9750 AA
Haren, The Netherlands. s.a.f.t....@rug.nl
Lactic acid bacteria (LAB) employ sucrase-type enzymes to convert
sucrose into homopolysaccharides consisting of either glucosyl units
(glucans) or fructosyl units (fructans). The enzymes involved are
labeled glucansucrases (GS) and fructansucrases (FS), respectively. The
available molecular, biochemical, and structural information on sucrase
genes and enzymes from various LAB and their fructan and alpha-glucan
products is reviewed. The GS and FS enzymes are both glycoside
hydrolase enzymes that act on the same substrate (sucrose) and catalyze
(retaining) transglycosylation reactions that result in polysaccharide
formation, but they possess completely different protein structures. GS
enzymes (family GH70) are large multidomain proteins that occur
exclusively in LAB. Their catalytic domain displays clear
secondary-structure similarity with alpha-amylase enzymes (family
GH13), with a predicted permuted (beta/alpha)(8) barrel structure for
which detailed structural and mechanistic information is available.
Emphasis now is on identification of residues and regions important for
GS enzyme activity and product specificity (synthesis of alpha-glucans
differing in glycosidic linkage type, degree and type of branching,
glucan molecular mass, and solubility). FS enzymes (family GH68) occur
in both gram-negative and gram-positive bacteria and synthesize
beta-fructan polymers with either beta-(2-->6) (inulin) or beta-(2-->1)
(levan) glycosidic bonds. Recently, the first high-resolution
three-dimensional structures have become available for FS
(levansucrase) proteins, revealing a rare five-bladed beta-propeller
structure with a deep, negatively charged central pocket. Although
these structures have provided detailed mechanistic insights, the
structural features in FS enzymes dictating the synthesis of either
beta-(2-->6) or beta-(2-->1) linkages, degree and type of branching,
and fructan molecular mass remain to be identified.
PMID: 16524921
Lactic acid bacteria inducing a weak interleukin-12 and tumor necrosis
factor alpha response in human dendritic cells inhibit strongly
stimulating lactic acid bacteria but act synergistically with
gram-negative bacteria.
Zeuthen LH, Christensen HR, Frokiaer H.
BioCentrum-DTU, Biochemistry and Nutrition Group, Technical University
of Denmark, Building 224, DK-2800 Kgs. Lyngby, Denmark.
l...@biocentrum.dtu.dk
The development and maintenance of immune homeostasis indispensably
depend on signals from the gut flora. Lactic acid bacteria (LAB), which
are gram-positive (G+) organisms, are plausible significant players and
have received much attention. Gram-negative (G-) commensals, such as
members of the family Enterobacteriaceae, may, however, be
immunomodulators that are as important as G+ organisms but tend to be
overlooked. Dendritic cells (DCs) are crucial immune regulators, and
therefore, the present study aimed at investigating differences among
human gut flora-derived LAB and G- bacteria in their patterns of DC
polarization. Human monocyte-derived DCs were exposed to UV-killed
bacteria, and cytokine secretion and surface marker expression were
analyzed. Profound differences in the DC polarization patterns were
found among the strains. While strains of LAB varied greatly in their
capacity to induce interleukin-12 (IL-12) and tumor necrosis factor
alpha (TNF-alpha), G- strains were consistently weak IL-12 and
TNF-alpha inducers. All strains induced significant amounts of IL-10,
but G- bacteria were far more potent IL-10 inducers than LAB.
Interestingly, we found that when weakly IL-12- and TNF-alpha-inducing
LAB and strong IL-12- and TNF-alpha-inducing LAB were mixed, the weakly
IL-12- and TNF-alpha-inducing LAB efficiently inhibited otherwise
strong IL-12- and TNF-alpha-inducing LAB, yet when weakly IL-12- and
TNF-alpha-inducing LAB were mixed with G- bacteria, they
synergistically induced IL-12 and TNF-alpha. Furthermore, strong IL-12-
and TNF-alpha-inducing LAB efficiently up-regulated surface markers
(CD40, CD83, CD86, and HLA-DR), which were inhibited by weakly IL-12-
and TNF-alpha-inducing LAB. All G- bacteria potently up-regulated
surface markers; however, these markers were not inhibited by weakly
IL-12- and TNF-alpha-inducing LAB. These much divergent DC stimulation
patterns among intestinal bacteria, which encompass both antagonistic
and synergistic relationships, support the growing evidence that the
composition of the gut flora affects immune regulation and that
compositional imbalances may be involved in disease etiology.
PMID: 16522779
OK. So much for the sweet terrain in the gut. Back to
the GrouP B streP thing.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16597875
Use of a Serotype-Specific DNA Microarray for Identification of Group B
Streptococcus (Streptococcus agalactiae).
Wen L, Wang Q, Li Y, Kong F, Gilbert GL, Cao B, Wang L, Feng L.
TEDA School of Biological Sciences and Biotechnology, Nankai
University, 23 HongDa Street, TEDA, Tianjin 300457, People's Republic
of China. feng...@nankai.edu.cn.
Group B Streptococcus (GBS; Streptococcus agalactiae) is an important
cause of sepsis and meningitis. Nine GBS serotypes, based on capsular
polysaccharide (CPS) antigens, have been described. Their distribution
varies worldwide and needs to be monitored to understand the
epidemiology of GBS disease and inform the development of vaccines. In
this study, we sequenced cpsH of GBS serotype II (cpsHII) and compared
it with that of the other eight serotypes to identify serotype-specific
regions. We then developed a DNA microarray based on the cpsH gene and
used it to test 88 GBS isolates-9 serotype reference strains and 79
clinical isolates-and 7 other bacterial and fungal species which are
commonly present in the vagina flora. The microarray was shown to be
specific and reproducible. This is the first report of a microarray
which can identify the nine GBS serotypes. The use of a microarray has
advantages over traditional serotyping methods and will be of practical
value in both reference and diagnostic laboratories.
PMID: 16597875
randall.... so much for lab/terrain/GrouP B strep today!
Mikhail Inq
Many thanks for this information.
Thes abstract is very interesting.
Unfortunately while the complete text of this paper is not accessible.
We shall try to get it.
I do not write in discussion as catastrophically there is no time.
We assume the important role of beta-hemolytic (!) streptococcuses at a
psoriasis.
It's not the same, as that streptococcuses group B!
See fragment of our paper:
Streptococci (genus Streptococcus) are facultative anaerobes.
Streptococci are classified in 17 groups designated by header Latin
letters depending on the presence of specific carbohydrates in a
cellular wall. There is a separate Braun's classification based on
streptococci growth peculiarities at an agar with ram's blood.
According to this classification scientists distinguish a-streptococci
(partial hemolysis and virescence of the medium, i.e. virescencing),
b-streptococci (completely hemolyzing or hemocatheretic) and
g-streptococcuses (producing invisible hemolysis).
Practically in each of groups (A, B, C, D....) _main_ part of
streptococcuses is beta-hemolytic. Concerning beta-hemolytic
streptococcuses see also
http://141.150.157.117:8080/prokPUB/chaphtm/276/COMPLETE.htm
First of all our suspicions concern to S.pyogenes and S.agalacteae.
Are thankful in advance for any new information on their interrelation
with a psoriasis.
As soon as the our new review will be ready - I necessarily shall
inform about it.
Mikhail
Mikhail Inq
a-streptococci == alfa-streptococci
b-streptococci == beta-streptococci
g-streptococci == gamma-streptococci
randall
Thank-you for your diligent reply and willingness to cure psoriasis.
As to group posts concerning the above,
http://groups.google.com/groups/search?q=.agalactiae+psoriasis&qt_s=Search
&
http://groups.google.com/groups/search?q=pyogenes+psoriasis&qt_s=Search
I hope you receive the study concerning the abstract from above. I
emailed
one of the authors to see if they would send it to you.
Back to P news...
-----------------------------------------------------------------------------------------------------
Will suPPlementing with Vitamin D bring relief from P?
http://www.nutraingredients.com/news/ng.asp?n=66953-vitamin-d-inflammation-chf
High-dose vitamin D supplements act as anti-inflammatory
By Stephen Daniells
10/04/2006 - A high-dose vitamin D supplement inhibit pro-inflammatory
and boost anti-inflammatory molecules and could help people with heart
failure, says a German clinical trial.
"We showed for the first time that a daily supplement of 50
micrograms vitamin D for nine months is able to increase serum
concentrations of the anti-inflammatory cytokine IL-10 and to prevent
an increase in serum concentrations of the pro-inflammatory cytokine
TNF-alpha in CHF patients," wrote lead author Stefanie Schleithoff
from the University of Bonn.
According to the Study on Heart failure Awareness and Perception in
Europe (SHAPE), about 14m people in Europe suffer from chronic heart
failure (CHF) with the number forecast to rise to 30 m by 2020. About
5m people suffer from the condition in the US.
The cause of CHF is not understood, but recent theories involve
increased levels of pro-inflammatory cytokines, such as tumour necrosis
factor alpha (TNF-alpha).
The randomised placebo-controlled trial, published in the April issue
of the American Journal of Clinical Nutrition (Vol. 83, pp. 754-759),
followed the effects of a high-dose vitamin D3 supplement (50
micrograms, equivalent to 2000 International Units) on cytokine levels
and heart pumping ability of 123 patients with CHF.
Both placebo and vitamin D supplement groups were also given a daily
supplement of 500 milligrams of calcium.
After nine months the researchers reported that serum levels of
25-hydroxyvitamin D, the non-active 'storage' form of the vitamin in
the body, increased by 26.8 nanograms per millilitre (ng/mL) from the
start of the study for the supplemented group, while the placebo
group's levels decreased by 3.6 ng/mL, a not-too-unexpected result.
Levels of TNF-alpha did not differ significantly before or after
supplementation with vitamin D, but it did increase by 12 per cent in
the placebo group. Interleukin 10 (IL-10) levels increased by an
impressive 43 per cent in the supplemented group, but did not change in
the placebo group.
No significant difference was observed in heart function, as measured
by left ventricular ejection fraction (LVEF), for either of the groups;
a result that differs from a previous study with lower vitamin D doses
(400 IU) that reported improvements in LVEF, but no improvement in
cytokine levels.
Twenty-five patients dropped out of the trial because of a worsening in
health. However, the authors point out that these patients all had
markedly higher levels of many pro-inflammatory markers at the start of
the trial.
In an accompanying editorial by Reinhold Vieth and Samantha Kimball
from the University of Toronto, said that the study offered two
important insights: "First, the article confirms previous evidence
that vitamin D supplementation affects immune-modulating cytokines in
desirable ways. Second, it points to a higher dose requirement for
achieving this."
Vitamin D has been reported to improve muscular function, control blood
pressure, and improve glucose tolerance, all of which underlying causes
of CHF, said Vieth and Kimball.
"The more realistic question raised by Schleithoff et al is whether
the use of an appropriate dose of vitamin D, as one part of a
nutritional strategy, could help in the primary prevention of CHF,"
concluded the editorial.
The results of this clinical trial appear to be in line with a study
published in the Journal of the American College of Cardiology (2003,
Vol. 41, pp. 105-112) which reported that heart disease was linked to
vitamin D deficiency.
----------------------------------------------------------------------------------------
The abstract for the above article.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16600924Vitamin
D supplementation improves cytokine profiles in patients with
congestive heart failure: a double-blind, randomized,
placebo-controlled trial.
Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P,
Koerfer R.
Institute of Nutrition and Food Science, University of Bonn, Bonn,
Germany.
BACKGROUND: Elevated circulating concentrations of proinflammatory
cytokines may contribute to the pathogenesis of congestive heart
failure (CHF). In vitro studies suggest that vitamin D suppresses
proinflammatory cytokines and increases antiinflammatory cytokines.
OBJECTIVE: We evaluated the effect of vitamin D supplementation on the
survival rate and different biochemical variables in patients with CHF.
DESIGN: One hundred twenty-three patients randomly received either 50
mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg
Ca/d [D(-) group] for 9 mo. Biochemical variables were assessed at
baseline and after 9 mo. The survival rate was calculated for a
follow-up period of 15 mo. RESULTS: Ninety-three patients completed the
study. Significant treatment effects were observed on
logarithmic-transformed serum concentrations of 25-hydroxyvitamin D (P
= 0.001), parathyroid hormone (P = 0.007), tumor necrosis factor alpha
(P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D
increased by 26.8 ng/mL in the D(+) group but increased only by 3.6
ng/mL in the D(-) group. Compared with baseline, parathyroid hormone
was significantly lower and the antiinflammatory cytokine interleukin
10 was significantly higher in the D(+) group after 9 mo. The
proinflammatory cytokine tumor necrosis factor alpha increased in the
D(-) group but remained constant in the D(+) group. The survival rate
did not differ significantly between the study groups during the
follow-up period. CONCLUSIONS: Vitamin D(3) reduces the inflammatory
milieu in CHF patients and might serve as a new antiinflammatory agent
for the future treatment of the disease. Our data provide evidence for
the involvement of an impaired vitamin D-parathyroid hormone axis in
the progression of CHF.
PMID: 16600924
While i'm on pubmed, i'll look for a few abstracts that I figure may be
helpful.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16601356
Type I Regulatory T Cells in Autoimmunity and Inflammatory Diseases.
Veldman C, Nagel A, Hertl M.
Department of Dermatology, University of Marburg, Marburg, Germany.
Regulatory T cells exert a critical role in controlling autoimmunity
and maintaining peripheral tolerance. The best described regulatory T
cells are the naturally occurring CD4+CD25+ regulatory T cells, which
have been shown to be continuously produced within the thymus. Other
T-cell subsets bearing suppressive capacity have been reported,
including T-helper-3 cells (Th3) and type 1 regulatory T (Tr1) cells.
Tr1 cells have been shown to be induced upon antigen exposure under
certain tolerogenic conditions and are characterized by the production
of the immunosuppressive cytokines IL-10 and TGF-beta, while Th3 cells
preferentially produce TGF-beta upon induction by intestinal tolerance.
Recent progress has been made in the characterization of Tr1 cells in
terms of isolation and induction, respectively. The present review
provides an overview of the presence of Tr1 cells in inflammation,
infection and neoplastic disorders. Moreover, the relationship between
different regulatory T cell subsets and their transcriptional control
is discussed. The recent development of methods allowing the ex vivo
expansion of regulatory T cells may be the first step towards a
cellular therapy with regulatory T cells to control T-cell-mediated
pathology in inflammatory disorders. Copyright (c) 2006 S. Karger AG,
Basel.
PMID: 16601356
Loss of SOCS3 in T helper cells resulted in reduced immune responses
and hyperproduction of interleukin 10 and transforming growth
factor-{beta}1.
Kinjyo I, Inoue H, Hamano S, Fukuyama S, Yoshimura T, Koga K, Takaki H,
Himeno K, Takaesu G, Kobayashi T, Yoshimura A.
Division of Molecular and Cellular Immunology, Medical Institute of
Bioregulation, 2Research Institute for Diseases of the Chest, Graduate
School of Medical Sciences, and 3Department of Parasitology, Faculty of
Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582,
Japan.
Suppressor of cytokine signaling (SOCS)3 is a major negative feedback
regulator of signal transducer and activator of transcription
(STAT)3-activating cytokines. Transgenic mouse studies indicate that
high levels of SOCS3 in T cells result in type 2 T helper cell (Th2)
skewing and lead to hypersensitivity to allergic diseases. To define
the physiological roles of SOCS3 in T cells, we generated T
cell-specific SOCS3 conditional knockout mice. We found that the mice
lacking SOCS3 in T cells showed reduced immune responses not only to
ovalbumin-induced airway hyperresponsiveness but also to Leishmania
major infection. In vitro, SOCS3-deficient CD4(+) T cells produced more
transforming growth factor (TGF)-beta1 and interleukin (IL)-10, but
less IL-4 than control T cells, suggesting preferential Th3-like
differentiation. We found that STAT3 positively regulates TGF-beta1
promoter activity depending on the potential STAT3 binding sites.
Furthermore, chromatin immunoprecipitation assay revealed that more
STAT3 was recruited to the TGF-beta1 promoter in SOCS3-deficient T
cells than in control T cells. The activated STAT3 enhanced TGF-beta1
and IL-10 expression in T cells, whereas the dominant-negative form of
STAT3 suppressed these. From these findings, we propose that SOCS3
regulates the production of the immunoregulatory cytokines TGF-beta1
and IL-10 through modulating STAT3 activation.
PMID: 16606674
SOCS3 moduated by STAT3?
STAT3 and P history,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=psoria*+stat3
*******************************************
Phospholipase D2 acts as an essential adaptor protein in the activation
of Syk in antigen-stimulated mast cells.
Lee JH, Kim YM, Kim NW, Kim JW, Her E, Kim BK, Kim JH, Ryu SH, Park JW,
Seo DW, Han JW, Beaven MA, Choi WS.
Department of Immunology, Konkuk University, Chungju, Korea.
Mast cells are responsible for IgE-mediated allergic reactions.
Phospholipase (PL) D1 and PLD2 regulate mast cell activation but the
mechanisms remain unclear. Here we show that PLD2 associates with and
promotes activation of Syk, a key enzyme in mast cell activation.
Antigen stimulation resulted in increased association and
co-localization of Syk with PLD2 on the plasma membrane as indicated by
co-immunoprecipitation and confocal microscopy. This association was
dependent on tyrosine phosphorylation of Syk, but not on PLD2 activity.
In vitro, PLD2 interacted via its Phox homology (PX) domain with
recombinant Syk to induce phosphorylation and activation of Syk.
Furthermore, overexpression of PLD2 or catalytically inactive PLD2K758R
enhanced antigen-induced phosphorylations of Syk and its downstream
targets, the adaptor proteins LAT and SLP-76, while expression of a
PLD2 siRNA blocked these phosphorylations. Apparently, the interaction
of PLD2 with Syk is an early critical event in the activation of mast
cells.
PMID: 16574950
Effects of arachidonic acid analogs on FcepsilonRI-mediated activation
of mast cells.
Nakano N, Nakao A, Uchida T, Shirasaka N, Yoshizumi H, Okumura K,
Tsuboi R, Ogawa H.
Atopy (Allergy) Research Center, Juntendo University School of
Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
nbna...@med.juntendo.ac.jp
Polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) have
been shown to modulate a number of inflammatory disorders. Mast cells
play a critical role in the initiation and maintenance of inflammatory
responses. However, the effects of PUFAs on mast cell functions have
not been fully addressed. We here-in examined the effects of PUFAs on
the high affinity IgE receptor (FcepsilonRI)-mediated mast cell
activation using RBL-2H3 cells, a rat mast cell line, that were
cultured in the medium containing palmitic acid (PA), AA, or the AA
analogs mead acid (MA) and eicosapentaenoic acid (EPA). In
AA-supplemented cells, the FcepsilonRI-mediated beta-hexosamidase and
TNF-alpha release, calcium (Ca(2+)) influx, and some protein tyrosine
phosphorylations including Syk and linker for activation of T cells
(LAT) were enhanced, whereas, in MA- or PA-supplemented cells, they
were not changed when compared with cells cultured in control medium.
In EPA-supplemented cells, the enhancements of beta-hexosamidase
release and protein tyrosine phosphorylations were observed.
Furthermore, in AA- or EPA-supplemented cells, FcepsilonRI-mediated
intracellular production of reactive oxygen species (ROS) that is
required for the tyrosine phosphorylation of LAT and Ca(2+) influx were
enhanced when compared with the other cells. Thus, preincubation of AA
or EPA augmented FcepsilonRI-mediated degranulation in mast cells by
affecting early events of FcepsilonRI signal transduction, which might
be associated with the change of fatty acid composition of the cell
membrane and enhanced production of ROS. The results suggest that some
PUFAs can modulate FcepsilonRI-mediated mast cell activation and might
affect FcepsilonRI/mast cell-mediated inflammation, such as allergic
reaction.
PMID: 16403671
LAT-mediated signaling in CD4+CD25+ regulatory T cell development.
Koonpaew S, Shen S, Flowers L, Zhang W.
Department of Immunology, Duke University Medical Center, Durham, NC
27710, USA.
Engagement of the T cell receptor for antigen (TCR) induces formation
of signaling complexes mediated through the transmembrane adaptor
protein, the linker for activation of T cells (LAT). LAT plays an
important role in T cell development, activation, and homeostasis. A
knock-in mutation at Tyr136, which is the phospholipase C
(PLC)-gamma1-binding site in LAT, leads to a severe autoimmune disease
in mice. In this study, we show that CD4+CD25+ T reg cells that
expressed Foxp3 transcription factor were nearly absent in both thymus
and peripheral lymphoid organs of LAT(Y136F) mice. This defect was not
a result of the autoimmune environment as LAT(Y136F) T reg cells also
failed to develop in healthy LAT-/- mice that received mixed wild-type
and LAT(Y136F) bone marrow cells. Moreover, adoptive transfer of normal
CD4+CD25+ T reg cells protected neonatal LAT(Y136F) mice from
developing this disease. These T reg cells effectively controlled
expansion of CD4+ T cells in LAT(Y136F) mice likely via granzymes
and/or TGF-beta-mediated suppression. Furthermore, ectopic expression
of Foxp3 conferred a suppressive function in LAT(Y136F) T cells. Our
data indicate that the LAT-PLC-gamma1 interaction plays a critical role
in Foxp3 expression and the development of CD4+CD25+ T reg cells.
PMID: 16380508
Gammadelta T cell-induced hyaluronan production by epithelial cells
regulates inflammation.
Jameson JM, Cauvi G, Sharp LL, Witherden DA, Havran WL.
The Scripps Research Institute, La Jolla, CA 92037, USA.
Nonhealing wounds are a major complication of diseases such as diabetes
and rheumatoid arthritis. For efficient tissue repair, inflammatory
cells must infiltrate into the damaged tissue to orchestrate wound
closure. Hyaluronan is involved in the inflammation associated with
wound repair and binds the surface of leukocytes infiltrating damaged
sites. Skin gammadelta T cells play specialized roles in keratinocyte
proliferation during wound repair. Here, we show that gammadelta T
cells are required for hyaluronan deposition in the extracellular
matrix (ECM) and subsequent macrophage infiltration into wound sites.
We describe a novel mechanism of control in which gammadelta T
cell-derived keratinocyte growth factors induce epithelial cell
production of hyaluronan. In turn, hyaluronan recruits macrophages to
the site of damage. These results demonstrate a novel function for skin
gammadelta T cells in inflammation and provide a new perspective on T
cell regulation of ECM molecules.
PMID: 15837812
The recognition pattern of gammadelta T cells.
Cao W, He W.
Department of Immunology, Institute of Basic Medical Sciences, Chinese
Academy of Medical Sciences and School of Basic Medicine, Peking Union
Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
caowe...@yahoo.com.cn
The main function of immune system is to recognize and respond to
foreign antigens. During the course of evolution, the body has
successfully developed four kinds of mechanisms to recognize antigens,
including pattern recognition mediated by macrophages, missing-self and
induced-self recognition for NK cells, antigen specific recognition for
alphabeta T cells and B cells and "broad-spectrum specific" recognition
for gammadelta T cells. The three formers have made great progress
these years. However, details of antigen recognition by gammadelta T
cells are still mysterious. Gammadelta T cells, a class of T cells only
existing in primates, differ from alphabeta T cells in TCR diversity,
the structure of TCR-CD3 complex, the tissue distribution, the antigens
that they recognize and the way involved in recognition. Here, we shed
light on the recognition mechanism of gammadelta T cells against
several known antigens and discuss the possible response pattern along
the research historical process. We put forward a recognition
hypothesis for gammadelta TCR that is conformational recognition based
on germline encoded recognition. The key germline encoded amino acids
dominate the "putative binding box" and are responsible for
recognition. Meanwhile, after gammadelta T cells are activated, several
other molecules such as CD69, CD16, 2B4, NKG2D also participate in
inducing cytotoxicity of activated gammadelta T cells. Obviously, the
illustration of recognition mechanism for gammadelta T cells will help
to comprehensively understand the whole immune system and design the
higher effective multi-epitope vaccines for tumor and infection
immunity.
PMID: 15970527
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
randall... the P quest is still afoot.
randall
randall wrote:
> Mikhail Inq wrote:
> > > I'm intending to send this next abstract off to Mikhail for his
> > > perspective on it.
> > >
> > > His Group B strep/gut theory as the cause of P is still on the table
> > > isn't it?
Sure!
<sniP>
Hi,
We haven't had one of these in awhile.
Human Psoriatic candle goes uP in smoke! No wait.... Fire!
http://www.worksoptoday.co.uk/ViewArticle2.aspx?SectionID=741&ArticleID=1455393
Excuse me? His P caught fire. YIKES
Eating all that fried fish and chiPs must have turned him in to a
sticky wick it.
Will others take notice?
YeP
Set uP local P groups in Ireland,
http://www.waterford-news.ie/news/story.asp?j=21548
Irish P meetings,
http://www.irishhealth.com/?level=4&id=9365
Meanwhile in India, a woman with P pulls a Gandhi,
http://www.tehelka.com/story_main17.asp?filename=Cr042906Revolutionary.asp
Gee! why treat her P? Doesn't the starvation clear it uP? he he
randall... he had only "nipped out for a crafty fag"
randall
TNF blocker drugs for obese people now?
Should that hapPen will it bring down the prices?
Or is this another gas squeeze situation that causes
an increase?
http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-58362.html
Blocking key protein reduces inflammatory markers in metabolic syndrome
Findings shed light on mechanism of condition associated with heart
disease, type 2 diabetes
Researchers from Massachusetts General Hospital (MGH) have shown, for
the first time, that blocking the action of a critical protein can
improve multiple inflammatory pathways in patients with the metabolic
syndrome - a cluster of symptoms associated with increased risk of
cardiovascular disease and type 2 diabetes. If supported in future
studies, the findings may suggest new strategies for improving the
cardiovascular risk in patients with the metabolic syndrome. This
preliminary report appears in the April 24 Archives of Internal
Medicine.
"This proof of principle sheds light on the physiology of inflammation
and its relation to cardiac risk in obese patients," says Steven
Grinspoon, MD, of the MGH Program in Nutritional Metabolism and
Neuroendocrine Unit, the report's senior author. "And it's the
first study of the medication etanercept, currently prescribed to treat
arthritis and psoriasis, used in patients with the metabolic syndrome."
Metabolic syndrome is a group of symptoms that includes abdominal
obesity, high triglycerides and LDL ("bad") cholesterol along with low
HDL ("good") cholesterol, insulin resistance or glucose intolerance,
and abnormal levels of several inflammatory proteins. The occurrence of
the syndrome is increasing, and it is estimated to affect more than 50
million Americans currently. Also called insulin resistance syndrome,
metabolic syndrome increases the risk of heart attack, stroke and other
cardiovascular disorders, as well as type 2 diabetes. While there are
many questions about the mechanism behind metabolic syndrome, current
evidence suggests that inflammatory proteins released by abdominal fat
may be an underlying cause of the increased cardiovascular risk.
One of the key inflammatory proteins released by fat cells is tumor
necrosis factor (TNF), which is known to increase insulin resistance
and the production of other inflammatory markers. Etanercept, marketed
under the brand name Enbrel, treats several inflammatory disorders by
blocking the action of TNF. The current study was designed to see
whether using the drug might also reduce the inflammatory effects of
metabolic syndrome, as measured by levels of C-reactive protein (CRP),
which also has been associated with increased risk of cardiovascular
disease.
The researchers enrolled 56 patients ages 37 to 54 who met standard
criteria for metabolic syndrome but did not have diabetes,
cardiovascular disease or any other inflammatory disorder. Half of them
received weekly injections of etanercept and half received a placebo
during the four-week study period. On each weekly visit, participants
also had a physical examination and blood tests for levels of glucose,
insulin and various markers including CRP.
At the end of the study period the CRP levels of participants who
received etanercept were 34 percent lower than those of participants
receiving the placebo. Levels of Interleukin-6 and fibrinogen, other
inflammatory factors associated with increased cardiovascular risk,
were also reduced in those who received the active medication; but
levels of adiponectin - a factor that reflects reduced inflammation
- had increased, also suggesting lower risk. No significant side
effects were reported.
"It has been speculated that blocking TNF could reduce systemic
inflammation in abdominally obese people, and we are very excited that
giving this drug had such a dramatic effect on these major markers,"
Grinspoon says. "We were surprised that it didn't also affect insulin
resistance, but that could be because the study was only four weeks
long. We're planning longer term studies to get a more complete
picture of how this strategy might someday be used to reduce the risks
associated with metabolic syndrome." Grinspoon is an associate
professor of Medicine at Harvard Medical School.
**************************************************************************
You want a little tickle? Don't eat the fish, let them eat you.
http://www.guardian.co.uk/japan/story/0,,1760744,00.html
------------------------------------------------------------------
That's it! We train the fish to eat our fat and P...I wonder.
Humans as fish food are most likely to high in omega-6's, rendering
the fish no better then farmed fish, fed n-6 pufa grains. lol
randall
randall
After that big, really BIG news from the NIH regarding connexin-26,
you can't expect much to follow that act.
WELL, lets get it over.
We have that whey derived product from Canada. Which is coming soon to
the
US...
http://www.ccnmatthews.com/news/releases/show.jsp?action=showRelease&searchText=false&showText=all&actionFor=591325
Advitech Inc Announces Agreement with Enbio-Life for Dermylex in Taiwan
[...]
DermylexTM is Advitech's orally administered product for mild to
moderate plaque psoriasis. DermylexTM is made from Advitech's XP-828L,
a bioactive ingredient with proven clinical efficacy. On July 5, 2005,
the Company reported positive results from its Phase II clinical trial
of XP-828L for treating mild to moderate psoriasis. The 112-day,
multi-center, double blind, placebo-controlled study, involving 84
patients, confirmed the efficacy and excellent safety profile of
XP-828L for treating mild to moderate psoriasis.
About Advitech
Advitech is a life science and technology company specializing in the
development of clinically tested bioactive ingredients for chronic
immune-mediated inflammatory diseases (IMID), such as psoriasis and
inflammatory bowel diseases. Advitech's common shares are listed on the
TSX Venture Exchange under the symbol AVI. The number of common shares
outstanding is 54,799,818.
<sniP>
----------------------------------------------------------
P news from cuba today. Well. A little any way.
http://www.caribbeannetnews.com/cgi-script/csArticles/articles/000013/001395.htm
randall note: i think they toss'ed in the P word to dress up the
article?
_________________________
How about some sexy stuff?
Some Love notes from Canada. Go to Rash Decisions - 2nd topic
http://www.eye.net/eye/issue/issue_04.27.06/theend/lovebites.html
[...]
Stroke It (calendula, chickweed, plantain, comfrey, sage) are
considered antimicrobial and soothing. Roger Lewis, a chartered
herbalist at Thuna Herbals (298 Danforth), confirms that all these
plants are used in salves designed to heal cuts and abrasions and are
also recommended in salves for women who have cracked nipples from
breastfeeding. Your only real concern, after ruling out eczema or
psoriasis, would be an allergy to beeswax, which is one of the
emollients in Stroke It. If this is an issue, simple shea butter would
also be appropriate, also available at Thuna.
They don't even mention where the stuff comes from.
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
Those herbs look really good. Put in some oregon grape (mahonia
aquifolium )
and go to town,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20Berberis
>From our grouP,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=oregon+grape&qt_g=1&searchnow=Search+this+group
Scroll back to see the whole thread on that first hit.
***********************************************
And most of those herbs are a lot cheaper then calaguala,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=calaguala&qt_g=1&searchnow=Search+this+group
Lets run the fern stuff and see,
http://froogle.google.com/froogle?group=alt.support.skin-diseases.psoriasis&q=calaguala&qt_g=1&searchnow=Search+this+group&sa=N&tab=gf
Hey! Not bad. Not bad at all....
randall... let's have a shamPoo and soaP Party !
randall
Psoriatic livers have problems due to low phase II enzymes like
glutathione peroxidase.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12679161
[..]
Plasma Selenium concentration and glutathione peroxidase (GSH-Px)
activity are low in
psoriatics <sniP>
VEGF for livers injured with LPS (endotoxins).
http://www.tmcnet.com/usubmit/2006/04/27/1617305.htm
Injured livers regenerate when given vascular endothelial growth factor
treatment
(Science Letter Via Thomson Dialog NewsEdge)
Injured livers regenerate when given vascular endothelial growth factor
(VEGF) treatment.
"The role of the VEGF, a potent angiogenic factor, in liver
regeneration following acute severe liver injury (ALI) has not been
elucidated. The aims of the current study were to investigate the role
of VEGF, and to find out whether VEGF can improve the outcome of ALI in
rats. ALI was induced in male rats by combination of D-galactosamine
(Gal-N) and lipopolysaccharide (LPS)," investigators in Japan report.
According to T. Namisaki and colleagues, Nara Medical University, "The
survival rate and several indices were chronologically compared with or
without VEGF treatment. The overall survival rate of the VEGF-treated
group significantly improved as compared with the untreated group (100%
vs. 27%, respectively).
"The serum ALT elevation, with a peak at 24 h after Gal-N + LPS
intoxication, was markedly attenuated with VEGF treatment. The
proliferation of hepatocytes and sinusoidal endothelial cells (SEC) was
stimulated by VEGF with a peak at 36 and 96 h, respectively. The
immunohistochemical analysis revealed that VEGF drastically prevented
destruction of the SEC architecture in ALI."
"Our in vitro study showed that VEGF significantly prevented the Gal-N
+ LPS-induced cytotoxicity and apoptosis of SEC. VEGF treatment
significantly reduced the mortality rate of ALI in the rat, and it may
provide a new therapeutic strategy for ALI," scientists indicated.
Namisaki and colleagues published their study in the Journal of
Hepatology (Salvage effect of the vascular endothelial growth factor on
chemically induced acute severe liver injury in rats. J Hepatol,
2006;44(3):568-575).
For additional information, contact H. Yoshiji, Nara Med University,
Dept. Internal Medicine 3, School of Medicine, Shijo Cho 840,
Kashihara, Nara 6348522, Japan.
The publisher of the Journal of Hepatology can be contacted at:
Elsevier Science BV, PO Box 211, 1000 AE Amsterdam, Netherlands.
Keywords: Nara, Japan, Acute Severe Liver Injury, Angiogenesis,
Apoptosis, Gastroenterology, Hepatology, Liver Regeneration, Vascular
Endothelial Growth Factor, Proteomics, Cytotoxicity.
This article was prepared by Science Letter editors from staff and
other reports.
*************************************************************
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16630077
Vascular endothelial growth factor gene polymorphisms increase the risk
to develop psoriasis.
Barile S, Medda E, Nistico L, Bordignon V, Cordiali-Fei P, Carducci M,
Rainaldi A, Marinelli R, Bonifati C.
Department of Dermatology, S. Gallicano Institute, Rome, Italy.
We investigated the relationship between eight polymorphisms in the
gene encoding for vascular endothelial growth factor (VEGF) (-1540C >
A, -1512Ins18, -1451C > T, -460T > C, -160C > T, -152G > A, -116G > A
and +405G > C) and plaque-type psoriasis stratified for age at onset,
gender and family history of dermatosis. For this purpose, 117 patients
with chronic plaque-type psoriasis and 215 healthy subjects were
enrolled. We found that being homozygous -1540AA, -1512InsIns, -1451TT,
-460CC and -152AA conferred a significant risk in developing psoriasis
compared with heterozygous (-1540CA, -1512 + Ins, -1451CT, -460CT and
-152AG) and homozygous genotypes (-1540CC, -1512 + +-1451CC, -460TT and
-152GG) grouped together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and
1.87, respectively]. Conversely, having the -116AA or +405GG genotype
did not significantly increase the risk of disease expression compared
with other genotypes of the same loci. Interestingly, we found that
-1540AA, -1512InsIns, -1451TT, -460CC and -152AA homozygous genotypes
have a significant two-fold increased risk in developing psoriasis
after the age of 40 years (late-onset psoriasis) (ORs = 2.19, 2.19,
2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively)
as compared with controls. On the contrary, we found no
phenotype-genotype association of the same magnitude among the patients
in whom psoriasis developed at or before the age of 40 years
(early-onset psoriasis) compared with controls. Genotype distributions
were not significantly different when cases and controls were
stratified either by gender or family history of psoriasis. Finally,
VEGF plasma concentration was not significantly different between
patients and controls and was not correlated with the severity of the
disease.
PMID: 16630077
http://en.wikipedia.org/wiki/Homozygous
http://en.wikipedia.org/wiki/Heterozygous
& a short gene thing,
http://mil.citrus.cc.ca.us/cat2courses/bio104/ChapterNotes/Chapter10notesLewis.htm
&
http://www.juvenon.com/jhj/vol3no03.htm
randall....HAppy suPPlementing!
randall
What does P have to do with boxing and Love?
Is it more then a word to toss around?
http://www.oxfordstudent.com/tt2006wk1/Columns/face_to_face
http://www.thesweetscience.com/boxing-article/3721/needs-heart-when-heart-broken/
Clever folks who write articles should be made to flake a mile
in a severe psoriatics skin first.
randall... don't you love it when you punch the mirror?
randall
P News has become boring to me again. Connexin-26 being the
peak and now it's all money over there,
http://news.google.com/nwshp?hl=en&tab=wn&q=psoriasis%20million
242 hits for P and $.
I guess you know what it's all about then?
Let's have fun instead. Find the food and link it uP...
When the Head of France makes fun of the cuisine of Finland,
what do you do?
http://www.kansascity.com/mld/kansascity/living/food/14424814.htm
{...]
Finland, a land of forests and lakes extending from the Arctic Circle
into the Baltic Sea, is known for its fish, wild game, and fresh
berries and vegetables that get an extra boost of flavor and size
during the long summer days of the midnight sun. Fish is prominent in
the cuisine of all Nordic countries, but because Finland has thousands
of lakes, freshwater fish play a more important role.
The abundant wild berries of Finland are used in desserts such as fruit
soups, whipped berry puddings and porridges.
"Juniper is classic in Finland," Lehtinen said, but his favorite is
the seabuckthorn berry. These deep orange berries smell rather like
pineapple and have so many vitamins and antioxidants that oil from the
berries is sold in health-food stores. The berries grow wild on thorny
bushes near the sea but are farmed as well.
Lehtinen uses the fruit for desserts. "It does well with ice cream,
sorbets, syrups and parfaits," he said. "We also make cocktails
with seabuckthorn berry juice. It takes care of your vitamin C level
for the rest of the year."
Like the wild berries, mushrooms are abundant in the forests of
Finland, where more than 100 varieties grow wild.
"It's fun to fall in love with something new every week,"
Lehtinen said. "In the summer the first new potatoes make people
crazy. You eat them with butter, dill and herring."
<sniP>.
---------------------------------------------
Has anyone with P tried seabuckthorn toPically?
Works great for folks with atopic dermatitis and some of us (Ben?) lean
towards a sebopsoriasis profile. Being Th1 and Th2 both!
http://groups.google.com/groups?qt_s=Search&ie=UTF-8&q=seabuckthorn+psoriasis&sa=N&tab=ng
http://news.google.com/news?qt_s=Search&ie=UTF-8&q=seabuckthorn%20psoriasis&sa=N&tab=gn
I just want to eat those things now!
If you want to try it do the froogle,
http://froogle.google.com/froogle?q=seabuckthorn&hl=en&btnG=Search
randall...froogle your google already!
randall
Todays post is aimed at Cruiser and Manfred. I'm hoping it's
helPful. :)
I was googling around on a few topics and these links
sorta came out of it.
This is what started it.
Alzheimer's fix in the works?
http://www.medicalnewstoday.com/medicalnews.php?newsid=42355
[...]
When TMP21 was first discovered, it appeared to be a "cargo
transporter" that embeds itself in the membranes of transport
vesicles--small, bladder-like sacs that shuttle proteins from one
cellular locale to another. St George-Hyslop's group discovered that
TMP21 moonlights by performing another distinct and independent role
within presenilin complexes.
To understand TMP21's role in presenilin complexes, the researchers
removed the protein from cells. What they saw surprised them:
amyloid-beta levels nearly doubled. Restoring TMP21 returned
amyloid-beta levels to normal.
TMP21 appears to keep amyloid-beta levels in check by preventing the
specific cleavage of APP that leads to its production. Remarkably,
TMP21 does not affect another cleavage also performed by the presenilin
complex, one that generates molecules that relay messages from one
nerve cell to another.
"Presenilin complexes don't just arbitrarily chop up proteins," said St
George-Hyslop. "The cleavage events involved in signaling and
amyloid-beta formation are separate, discretely regulated processes.
These data suggest that the presenilin complexes are likely to be as
complex and as important as the proteasome (a complex structure inside
the cell that breaks down proteins) in cleaving proteins, as the
function of the complex is dependent on key proteins that regulate its
activity."
Identification of TMP21 in presenilin complexes and its role in
amyloid-beta formation may change the way researchers design drugs for
Alzheimer's treatment.
<sniP>
-------------------------------------------------------------------
More hands-on folks may want to first try this alz cocktail instead for
the time being.
Uridine, choline and fish oils (n-3 efa's),
http://www.innovations-report.de/html/berichte/medizin_gesundheit/bericht-58487.html
randall note::: we already take two of these. But uridine didn't look
to familiar.
---------------------------------------------------------------
Could uridine be Uwe's secret anti-depressant?
http://groups.google.com/groups/search?ie=UTF-8&q=uridine+beets&qt_s=Search
(take out keyword beet for many more posts)
Uwe did post it twice,
http://groups.google.com/groups/search?ie=UTF-8&q=uridine+uwe&qt_s=Search
----------------------------------------------------
Are we on the wrong track with the lactoferrin or is it a marker of
inflammation?
http://groups.google.com/groups/search?q=lactoferrin+psoriasis+pete&qt_s=Search
Does uridine explain Uwe's rock hard you know whats?
http://www.google.com/search?q=uridine%20erection&qt_s=Search&sa=N&tab=gw
May as well see what the Life extension group has on it,
http://groups.google.com/group/sci.life-extension/search?group=sci.life-extension&q=uridine&qt_g=1&searchnow=Search+this+group
I now wondering if uwe used uridine with NAC, vitamin C, d-glucarate,
choline, n-3,
etc And whats the problem for us and lactoferrin?
Is that another reason for the dairy allergen problem so many of us
have?
And if that's partly true, do we get it seasonally due to a viral n the
sPring?
To many questions and not enough time... lol
_____________________________________________
Back to real P News.
More on IL-20 ,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16645593
Prominent Production of IL-20 by CD68(+)/CD11c(+) Myeloid-Derived Cells
in Psoriasis: Gene Regulation and Cellular Effects.
Wang F, Lee E, Lowes MA, Haider AS, Fuentes-Duculan J, Abello MV,
Chamian F, Cardinale I, Krueger JG.
[1] 1Laboratory for Investigative Dermatology, The Rockefeller
University, New York, New York, USA [2] 2These authors contributed
equally to this work.
We assessed expression of IL-20 and its receptors in psoriasis, given
the recent implication of IL-20 in epidermal hyperplasia. Psoriatic
lesional (LS) skin consistently expressed more IL-20 mRNA than
nonlesional (NL) skin. Immunoreactivity to IL-20 protein was greater in
LS tissue and mainly localized to infiltrating CD68(+)/CD11c(+)
(myeloid-derived) dermal leukocytes. Because this contrasted with
earlier reports of a keratinocyte source, we assessed IL-20 mRNA
expression in a variety of cells in vitro, and confirmed a
myeloid-derived cellular source (monocytes). Plastic adhesion,
activation of beta2 integrins, and incubation with tumor necrosis
factor-alpha stimulated expression in these cells. IL-20 receptor
(IL-20R)alpha and IL-20Rbeta mRNA was decreased in LS versus NL skin,
which also contrasted with earlier findings. To investigate the
relationship between IL-20 and disease activity, we examined psoriasis
patients treated with the CD2-targeted agent alefacept. In therapeutic
responders, lesional IL-20 mRNA decreased to NL levels, suggesting that
CD2(+) leukocytes may proximally regulate IL-20. Finally, to assess
IL-20 function, we used microarrays to screen IL-20-treated
keratinocytes, which demonstrated upregulation of disease-related and
IFN-gamma-induced genes. Hence, IL-20 may influence inflammation
through IFN-like effects. Together, these data indicate that IL-20 may
be an important effector cytokine in psoriasis, and that its inhibition
may represent a potential therapeutic target.Journal of Investigative
Dermatology advance online publication, 27 April 2006;
doi:10.1038/sj.jid.5700310.
PMID: 16645593
Calls for a cd(2)+ check,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=cd(2)+
And try keyword skin,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=cd(2)+skin
And i'm outa time,
randall.... sheesh, just when this was getting hot.
randall
P news from around the world. As endotoxin (LPS) has been on my radar
forever now,
lets start there.
LPS blunted by lactoferrin will help your gums.
http://www.tmcnet.com/usubmit/2006/04/29/1625049.htm
[...]
Lipopolysaccharide (LPS), a periodontal pathogen, reduces the level of
collagen in the gum tissue and breaks the tissue down.
Further, they have confirmed that lactoferin (LF), a kind of
multifunctional protein found in milk and breast milk, can detoxify LPS
so that it helps control the development of periodontal disease.
Details of the research will be presented at the 49th Annual Meeting in
Spring for the Japanese Society of Periodontology scheduled on April 28
and 29.
------------------------------------------------------------------------------------------
The rest of p news from google doesn't do it. Whatever *it* is? <g>
Abstract time:
A family of skin genes are showing their faces.
Purification, crystallization and preliminary X-ray diffraction of
human S100A15.
Boeshans KM, Wolf R, Voscopoulos C, Gillette W, Esposito D, Mueser TC,
Yuspa SH, Ahvazi B.
X-ray Crystallography Facility, NIAMS, National Institutes of Health,
Bethesda, MD 20892, USA.
Human S100A15 is a novel member of the S100 family of EF-hand
calcium-binding proteins and was recently identified in psoriasis,
where it is significantly upregulated in lesional skin. The protein is
implicated as an effector in calcium-mediated signal transduction
pathways. Although its biological function is unclear, the association
of the 11.2 kDa S100A15 with psoriasis suggests that it contributes to
the pathogenesis of the disease and could provide a molecular target
for therapy. To provide insight into the function of S100A15, the
protein was crystallized to visualize its structure and to further the
understanding of how the many similar calcium-binding mediator proteins
in the cell distinguish their cognate target molecules. The S100A15
protein has been cloned, expressed and purified to homogeneity and
produced two crystal forms. Crystals of form I are triclinic, with
unit-cell parameters a = 33.5, b = 44.3, c = 44.8 angstroms, alpha =
71.2, beta = 68.1, gamma = 67.8 degrees and an estimated two molecules
in the asymmetric unit, and diffract to 1.7 angstroms resolution.
Crystals of form II are monoclinic, with unit-cell parameters a = 82.1,
b = 33.6, c = 52.2 angstroms, beta = 128.2 degrees and an estimated one
molecule in the asymmetric unit, and diffract to 2.0 angstroms
resolution. This structural analysis of the human S100A15 will further
aid in the phylogenic comparison between the other members of the S100
protein family, especially the highly homologous paralog S100A7.
PMID: 16682778
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=S100A15
----------------------------------------------------------------------------------------------
These scientists in Turkey are A-OK in my book.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16684279
The effects of calcipotriol and methylprednisolone aseponate on bcl-2,
p53 and ki-67 expression in psoriasis.
Adi5en E, Gulekon A, Erdem O, Dursun A, Gurer M.
Department of Dermatology, Gazi University Faculty of Medicine, Ankara,
Turkey.
Objective The decrease of physiological apoptosis in the psoriatic
lesions is thought to be involved in the pathogenesis of psoriasis, and
induction of apoptosis was shown to contribute to the regression of
psoriatic hyperplasia. In the present study, we compared the effects of
calcipotriol and methylprednisolone aseponate (MPA) treatments on
bcl-2, p53 and ki-67 expressions in psoriatic patients in order to
define a relationship between regulation of apoptosis and healing
process in psoriasis. Methods Thirty psoriatic patients with stable and
moderate chronic plaque psoriasis applied either calcipotriol or MPA
ointment for 6 weeks twice daily. Evaluation of bcl-2, p53 and ki-67
positivity was performed at baseline and was repeated at sixth week for
each therapy. Results The mean percentage of positive keratinocytes was
8.63 +/- 7.15% for p53, 20.66 +/- 14.45% for ki-67, and 3.74 +/- 2.83%
for bcl-2 in psoriatic skin at baseline. Normal skin values were 3.27
+/- 3.21% for p53, 4.93 +/- 4.77% for ki-67, and 1.80 +/- 0.41% for
bcl-2. The psoriatic skin showed higher ki-67 (P < 0.05) and bcl-2 (P <
0.05) expression rates when compared to normal skin. The p53 positivity
observed in psoriatic skin and normal skin was not significantly
different (P > 0.05). Following calcipotriol and MPA treatments, there
was a significant reduction in p53 and ki-67 positivity accompanied by
an increase in bcl-2 positivity (P < 0.05 each). No significant
differences were found at sixth week between calcipotriol and MPA
groups with respect to p53, ki-67 and bcl-2 positivity (P > 0.05). The
post-treatment psoriatic skin showed lower expression of p53, higher
expressions of ki-67 and bcl-2 when compared to normal skin (P < 0.05
each). Conclusion The results of this study provide evidence that both
calcipotriol and MPA decrease the p53 and ki-67 expression and increase
bcl-2 expression. However, it should further be elucidated if these
changes were the common behaviour of psoriatic keratinocytes to any
antipsoriatic medication.
PMID: 16684279
-----------------------------------------------------------------
Back to the toPics du jour? That last thread I was in, i felt like a
piece of
HAM between two slices of sPam. lol
When will i see the light? lol or find the baloon vine?
Since we've been looking at ATp
http://en.wikipedia.org/wiki/Adenosine_triphosphate
And it hasn't really gone anywhere yet. I suppose one of us could try
X?
Or should we do the niacin thing again?
We've had folks who said they cleared upon taking niacin. If you ask me
to credit
flushing or oxygen increase, it simply doesn't make sense to me. Could
some other psoriasis pathway be involved? LOok at our marathon man, his
p didn't clear from
his strenuous exercise program till he changed his diet. You exercise
you get the
benefits. But the psoriatic doesn't till he stops the crap in his diet.
So it must be in the genes.
And how does that get us from psors1,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15333584
To a pathway like PLA(2) and arachidonic acid implications for P?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20psoriasis+arachidonic
To the effects of arachidonic acid and PLA(2)?,
http://www.acnp.org/g4/GN401000059/CH059.html
So what's uP with niacin and arachidonic acid? Put those in the
spotlight,
Enhancement of arachidonic acid signaling pathway by nicotinic acid
receptor HM74A.
Tang Y, Zhou L, Gunnet JW, Wines PG, Cryan EV, Demarest KT.
Endocrine Therapeutics and Metabolic Disorders, The Johnson and Johnson
Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan,
NJ 08869, USA.
HM74A is a G protein-coupled receptor for nicotinic acid (niacin),
which has been used clinically to treat dyslipidemia for decades. The
molecular mechanisms whereby niacin exerts its pleiotropic effects on
lipid metabolism remain largely unknown. In addition, the most common
side effect in niacin therapy is skin flushing that is caused by
prostaglandin release, suggesting that the phospholipase A(2)
(PLA(2))/arachidonic acid (AA) pathway is involved. Various eicosanoids
have been shown to activate peroxisome-proliferator activated receptors
(PPAR) that play a diverse array of roles in lipid metabolism. To
further elucidate the potential roles of HM74A in mediating the
therapeutic effects and/or side effects of niacin, we sought to explore
the signaling events upon HM74A activation. Here we demonstrated that
HM74A synergistically enhanced UTP- and bradykinin-mediated AA release
in a pertussis toxin-sensitive manner in A431 cells. Activation of
HM74A also led to Ca(2+)-mobilization and enhanced bradykinin-promoted
Ca(2+)-mobilization through Gi protein. While HM74A increased ERK1/2
activation by the bradykinin receptor, it had no effects on
UTP-promoted ERK1/2 activation.Furthermore, UTP- and
bradykinin-mediated AA release was significantly decreased in the
presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF
109203X. However, the synergistic effects of HM74A were not
dramatically affected by co-treatment with both inhibitors, indicating
the cross-talk occurred at the receptor level. Finally, stimulation of
A431 cells transiently transfected with PPRE-luciferase with AA
significantly induced luciferase activity, mimicking the effects of
PPARgamma agonist rosiglitazone, suggesting that alteration of AA
signaling pathway can regulate gene expression via endogenous PPARs.
PMID: 16674924
Activation of P2Y receptor enhances high-molecular compound absorption
from rat ileum.
Kinoshita N, Takahashi T, Tada S, Shinozuka K, Mizuno N, Takahashi K.
Departments of Pharmaceutics and Pharmacology, School of Pharmaceutical
Sciences, Mukogawa Women's University, 11-68 Koshien, Kyuban-cho,
Nishinomiya 663-8179, Japan.
While there are no reports concerning the effects of extracellular
nucleotides on the intestinal absorption of drugs, it is well known
that extracellular nucleotides are important regulators of intestinal
epithelial ion transport. This report using fluorescein isothiocyanate
dextran 4000 (FD-4) as the model compound is the first to investigate
the effects of purine nucleotides on absorption of poorly absorbed
drugs from intestine. ATP enhanced the absorption of FD-4 from rat
ileum in a concentration-dependent manner. ADP also enhanced the
absorption of FD-4. Other purine nucleotides (adenosine, AMP, UTP and
UDP) did not show an absorption-enhancing effect. The
absorption-enhancing effect by ATP was inhibited by suramin and
pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (PPADS), which are
known P2 receptor antagonists. Additionally, 2-methylthio ATP (a P2Y
receptor agonist) enhanced the absorption of FD-4, but
alpha,beta-methylene ATP (a P2X receptor agonist) did not. These
findings suggest that activation of the P2Y receptor may improve the
absorption of water-soluble and high-molecular compounds from the
ileum.
PMID: 16451747
While i haven't tied everything to-gether once again, we do have some
of those players back on the table. But as always, I still venture the
P gene thing as the PRIME culprit.
Just look again at the genes for psors1 and tell me we lack some
nutrient that can
be toPPed off Uwe style.
I don't see anyone barking uP the uridine sugar extract suPPlements
yet?
You can modulate uridine enzymes with beer I suPPose,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16673211
OTOH we know that ethanol (alcohol) will increase LPS and TNF and that
sPells more P severity,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12198380
Yet, is it a gene or chicken and egg thing for LIVER, alcohol and which
way the T helper
cells manifest themselves?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14745315
One thing has always been CLEAR to me. You can't drink alcohol and be
CLEAR.
But what is the Th1 skew of psoriasis due too?
Does some otherwise minor virus keep us skewed to the Th1 side and fuel
the
P genes in the skin? Is LPS only another marker like CRP in this
inflammatory
game?
And why now that i've figured out the IP6 usage to control iron?
Did my metals go back into homeostasis via IP6 and allow me to simply
clear quicker
now? I did flare back to normal levels (for the last 5-6 years my
spring fling p has been
in a range of 6-12% pasi) this year but i'm clearing without the help
of the sun very
quickly. And i've been using the ip6 for about 10 months. Whats
different this time
is vitamin C with it. I take 2-6 grams every day now. While I felt in
the past that
vitamin C soaked up the iron and contributed to p severity, i now feel
that it's beneficial
and that the ip6 allows the C to do it's work while blunting iron
effects.
But once again all of this is downstream of something else. And i'm
starting to
look at the viral thing again.
Maybe they kick the stats that jump start the Jun proteins? Taking us
back to
ap-1?
randall... does his sPing fling with less P this year! But cheer will
be a clear year!
randall
What is psors1?
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=177900
to
http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?l177900
Someone asked me that off group. In response to the previous post shown
below.
First,
How do genes work?
http://www.thetech.org/genetics/art02_how.php
Looking at each gene that makes uP the P gene, that we can't get back
in the
bottle yet. <w>
HLA-C
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142840
CDSN
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=OMIM&dopt=Detailed&tmpl=dispomimTemplate&list_uids=602593
Hcr
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=OMIM&dopt=Detailed&tmpl=dispomimTemplate&list_uids=605310
or
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605310
&
http://hmg.oxfordjournals.org/cgi/content/abstract/13/15/1551
Seeing their positions may help,
http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?d3016
& down the gene,
http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?l142840
And their maps, (HLA-C)
http://www.ncbi.nlm.nih.gov/mapview/maps.cgi?ORG=hum&CHR=6&maps=loc-r,morbid,gene&R1=on&query=HLA-C&VERBOSE=ON&ZOOM=3
H'mmmm I see that IP3 sits right next door to psors1. And I get plenty
of help from taking IP6.
IP3,
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606993
I"ll have to check out the gene function.
Yet taking IP6 is actually doing something!
randall... genes are fun to moduate, provided you clear a little or a
lot for that matter!
randall
One mom with P,
http://www.redding.com/redd/nw_columnists/article/0,2232,REDD_17528_4697651,00.html
happy mothers day!
randall.. it will be better with a cure some day.
randall
This next bit of info comes from a person who was a chemist and made up
his
own topical for skin cancer.
I asked him if he would be ok with my reposting his preparation here.
This is what he said:
"Re posting info about AMC: Permission not needed, I want to publicize
it. Incidentally, the letters, AMC, came from Antimitotic Composition,
the title of my ill-fated patent application.
I have always used 5% Efudex as a source of FU, mixed into 99.7% DMSO
in the ratio, one to four, giving a final 1% FU. It may be or not be
better to use 5% Adrucil. The cream components of Efudex make the mix
slightly viscous which is helpful in the application. I have seen no
adverse indication of the cream components being carried into the skin.
The cream base of Efudex is a Vanishing Cream. Don't forget the caveats
in use of Efudex. They are the same for AMC. Shelf life is at least a
few momths. For storage use glass or plastic Nos. 2 or 4. It is
conveniently applied with a soft brush. Avoid or test synthetic fibers"
This is his post that got my attention.
http://groups.google.com/groups/search?hl=en&q=ernsteele+cancer+efudex&qt_s=Search
Ernest is a nice gentleman and north of 90 y's/o.
We traded emails for about a week.
His use of DMSO with the Efudex is what initially caught my eye.
As we have folks here with P that responds to fungal treatments i
posted this
for their eyes as well..
Good luck.
***********************
Will something finally come along that leads to a cure for obesity?
http://www.nature.com/news/2006/060508/full/060508-12.html
Published online: 11 May 2006; | doi:10.1038/news060508-12
Protein fragment curbs appetite
Rats eat less than normal if injected with amino acid.
Helen Pearson
There is a building block of protein that kills hunger in the brain,
researchers have shown in experiments with rats. The result backs the
idea that altering tiny quantities of particular nutrients in our diets
could help fight obesity and disease.
The study suggests that rats' brains monitor levels of amino acids, the
components of proteins, and use this to judge how much food to eat. The
researchers, at the University of Cincinnati, Ohio, found that
injecting an amino acid called leucine into the brains of hungry rats
curbed their appetite: they gained a third less weight over 24 hours
than rats that didn't have jabs. The team reports its results in
Science1.
The discovery implies that traditional thinking about diets - based
on monitoring the broader classes of carbohydrates, fats and proteins
- is rather crude.
Tinkering with our diets more subtly, to include particular cocktails
of 'micronutrients' such as amino acids, sugars or fat components,
might help to control weight, alter aspects of metabolism and perhaps
combat disease.
Nutrient cocktails
"We have to stop thinking of nutrients as just energy or protein
sources," says Luciano Rossetti at Albert Einstein College of Medicine
in New York City, who is a proponent of this more subtle approach to
diet. Micronutrients are also biologically active molecules, he points
out.
Earlier studies have shown that lowering levels of oleic acid, the
major fatty component of olive oil, could dampen animals' appetites,
says Rossetti. And eating the amino acid L-phenylalanine, which is
found in some vegetables, juices, yogurt and artificial sweeteners, has
been shown to release a hormone called cholecystokinin, which in turn
seems to suppress human appetite2.
The notion that leucine gleaned from protein in foods, such as meat and
eggs, might do the same by having a direct impact on the brain is so
far speculative. The team doesn't know for sure whether leucine needs
to be injected to penetrate the brain, nor do they know if it works in
humans to suppress appetite.
"My worst fear is that someone is going to be selling leucine on the
Internet because of this," says Randy Seeley, who led the research.
Brain food
Certain neurons in the brain's hypothalamus carefully regulate our
appetite and weight, by monitoring long-term fat stores. In the past
few years, researchers have also started to understand how the same
circuits keep an eye on the minute-by-minute changes in circulating
nutrients.
Seeley's team studied a protein called mTOR (mammalian target of
rapamycin), which is known to work in most cells of our bodies to
detect fuel levels and decide whether an individual cell has the
resources to grow. The researchers wanted to see whether it also senses
fuel in the brain, and so directs an animal's eating behaviour as a
whole.
The team found that mTOR is active in the neurons that control appetite
in the hypothalamus, and that leucine boosts the activity of mTOR. This
makes rats eat less than they would normally. The researchers also
showed that leptin, a hormone that tells the body how much fat we are
carrying, activates mTOR as well.
The team proposes that mTOR may be a molecule central to appetite
control, although probably one of many. The various weight-control
hormones such as leptin, plus the circulating fats, sugars and proteins
could all influence the activity of mTOR, which in turn would regulate
feeding.
"This idea could integrate all those things very nicely," says Martin
Myers, who studies mechanisms of appetite control at University of
Michigan Medical School in Ann Arbor.
^^^^^^^^^
We have had mTor postings here,
http://groups.google.com/groups/search?q=mtor+psoriasis&qt_s=Search
-------------------------------------------------------------------
http://news.biocompare.com/newsstory.asp?id=133908
Gone to POT yet?
http://www.psychiatrictimes.com/showArticle.jhtml?articleID=185303874
&
http://www.psychiatrictimes.com/showArticle.jhtml?articleID=185303874
Obviously you can't toke on down the old fashion way or you'll have the
munchies
24/7 and that could lead to diabetes and a host of problems beyond your
health.
Taken from a news letter I receive on fridays,
(i liked the way it was written)
"DEPRESSION: CORTISOL LEVELS AND THE NEWS FROM WASHINGTON.
When our Pleistocene ancestors saw movement in the tall grass,
their brains released stress hormones, increasing heart rate
and respiration, dilating eyes to increase awareness and
diverting blood from the digestive tract to arms and legs.
The body was preparing to fight, or run very fast in the
opposite direction. Carnivores in the tall grass are not a
problem today, but there is plenty to fear. It's a lousy
feeling that hits you right in your blood-deprived stomach.
If anxiety persists due to war in Iraq, terrorists, bird flu,
arctic melting, gas prices, or Rumsfeld, the brain switches to
a long-term strategy. The hypothalamus, which controls
emotion, tells the adrenal cortex to release cortisol, another
stress hormone that raises blood pressure and increases blood
glucose levels. New findings from Harvard Medical School
links cortisol levels directly to depression for the first
time. You're being manipulated by your hypothalamus. You can
try to persuade your brain that there are no tigers, or take
antidepressants that boost serotonin, another hormone that
constricts blood vessels, countering the cortisol."
Is the stress of the munchies creating more cortisol?
---------------------------------------------------
How does one control this sugar urge then? With out the mind triPs?
The sugar studies are on going. In this case it's a sugar that died out
a long time ago in a galaxy far far away. <g>
http://www.indolink.com/displayArticleS.php?id=050406105803
04 May 2006 -- A significant difference between human and chimpanzee
immune cells may provide clues in the search to understand the diverse
array of human immune-related diseases, according to new findings by
Ajit Varki and his team at the University of California, San Diego
(UCSD) School of Medicine.
The team of researchers has uncovered a specific type of molecule
expressed on non-human primate T cells, but not human T cells. T cells
are important orchestrators of the immune system.
In a study to be published on-line in advance of publication in
Proceedings of the National Academy of Sciences the week of May 1-5,
UCSD researchers report that - unlike T cells from chimpanzees, and
gorillas (the "great apes" which are human's closest evolutionary
relatives) - human T cells lack expression of certain "Siglec"
molecules.
Siglecs are immune-dampening proteins that bind to sialic acids, the
complex sugars found on the outside of cells. Siglec molecules seem to
regulate T cell activation in chimpanzees by restricting the degree of
signaling from the T cell receptor, which normally triggers the
response of T cells in the immune system.
"Siglecs are like 'brakes' that can slow down the activation of
an immune cell upon stimulation," said Ajit Varki, M.D., UCSD
Professor of Medicine and Cellular and Molecular Medicine and
co-director of UCSD Glycobiology Research and Training Center.
"During human evolution, we seem to have shut off these brakes on our
T cells, allowing them to become hyper-active."
The explanation for this human-specific evolutionary loss of Siglecs is
currently unknown. The UCSD scientists speculate that this may have
been due to a selective pressure by a microbe that once drove human
ancestors to require a high level of T cell activation. Another
possibility is that this phenotype was secondarily acquired, during the
adjustment to the human-specific loss of the sialic acid Neu5Gc some
three million years ago, and that the phenotype has been carried by all
humans ever since.
The study raises warning flags about the stimulatory and potentially
destructive potential of the absence of Siglec molecules in human T
cells, compared to chimpanzees and other nonhuman primate counterparts.
This may explain some major differences in susceptibility to certain
diseases between humans and great apes. One example is the lack of
progression to AIDS in the great majority of chimpanzees infected with
HIV virus. It could also account for the rarity of T-cell mediated
liver damage, such as chronic active hepatitis, cirrhosis and cancer,
following Hepatitis B or C infection in chimpanzees. In addition,
several other common human T cell-mediated diseases, including
bronchial asthma, rheumatoid arthritis and type 1 diabetes, have, so
far, not been reported in chimpanzees or other great apes.
The study suggests that the expression of Siglecs on chimpanzee T cells
in essence puts the brakes on the cells during chronic HIV infection,
preventing progression to AIDS in chimpanzees. In contrast, the onset
of human AIDS occurs more rapidly due to the loss of T cells, which are
essentially "unprotected" by the regulatory Siglecs.
This study may also explain the severe human reactions observed in a
recent clinical trial using a T cell activating anti-CD28 antibody
produced by TeGenero, Inc. All six healthy volunteers who received
doses at 500 times lower than what was tested in nonhuman primates
became severely ill, requiring hospitalization.
"In retrospect, the absence of natural restrictions on activation,
such as that provided by Siglecs, could have predicted this striking
disparity between humans and nonhuman primates," said Varki. The
human volunteers could have experienced rapid activation of T cells and
a resulting "cytokine storm." The research team asked for a sample
of the anti-CD28 antibody from TeGenero in order to test it on
chimpanzee blood, but the company declined their request.
While this family of molecules displays a striking difference between
humans and nonhuman primates, the researchers point out that there may
be other undiscovered factors that also contribute to the observed
differences in immune function.
As our closest evolutionary cousins, chimpanzees share more than 99%
identity in typical protein sequences with humans. For that reason, the
common chimpanzee has long been assumed to be an effective animal model
for human diseases.
"In fact, chimpanzee diseases may be much more disparate from human
diseases than previously envisioned," said Varki.
"The good news is that the loss of this brake system is not
permanent, as we still have the Siglec genes in our genomes, and do
continue to express them in other blood cell types," said Varki.
"It is reasonable to hope that drugs can be found to turn the Siglec
brakes back on again in human T cells, to slow the T cells down when
they become hyper-active and cause disease."
*****************************
And sialic acid may be the responsible agent for that trial recently
where the guys looked like the elephant man.
http://arstechnica.com/journals/science.ars/2006/5/3/3829
&
http://loom.corante.com/archives/2006/05/02/wanted_hominids_for_clinical_drug_trials.php
&
TGN1412,
http://www.timesonline.co.uk/article/0,,2-2160469,00.html
randall... looking like a psoriatic is better then having a huge head!
randall
Sugars in the gut and other squirmy things.
Can we learn from diabetes and these sugary things?
In the last post we had a nice article that this abstract goes along
with,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16682635
Loss of Siglec expression on T lymphocytes during human evolution.
Nguyen DH, Hurtado-Ziola N, Gagneux P, Varki A.
Glycobiology Research and Training Center and Departments of Medicine
and Cellular and Molecular Medicine, and Biomedical Sciences Graduate
Program, University of California at San Diego, La Jolla, CA 92093.
We report here that human T cells give much stronger proliferative
responses to specific activation via the T cell receptor (TCR) than
those from chimpanzees, our closest evolutionary relatives. Nonspecific
activation using phytohemagglutinin was robust in chimpanzee T cells,
indicating that the much lower response to TCR simulation is not due to
any intrinsic inability to respond to an activating stimulus.
CD33-related Siglecs are inhibitory signaling molecules expressed on
most immune cells and are thought to down-regulate cellular activation
pathways via cytosolic immunoreceptor tyrosine-based inhibitory motifs.
Among human immune cells, T lymphocytes are a striking exception,
expressing little to none of these molecules. In stark contrast, we
find that T lymphocytes from chimpanzees as well as the other closely
related "great apes" (bonobos, gorillas, and orangutans) express
several CD33-related Siglecs on their surfaces. Thus, human-specific
loss of T cell Siglec expression occurred after our last common
ancestor with great apes, potentially resulting in an evolutionary
difference with regard to inhibitory signaling. We confirmed this by
studying Siglec-5, which is prominently expressed on chimpanzee
lymphocytes, including CD4 T cells. Ab-mediated clearance of Siglec-5
from chimpanzee T cells enhanced TCR-mediated activation. Conversely,
primary human T cells and Jurkat cells transfected with Siglec-5 become
less responsive; i.e., they behave more like chimpanzee T cells. This
human-specific loss of T cell Siglec expression associated with T cell
hyperactivity may help explain the strikingly disparate prevalence and
severity of T cell-mediated diseases such as AIDS and chronic active
hepatitis between humans and chimpanzees.
PMID: 16682635
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=siglec*
Moving on with this. But don't we already have good bugs to stop P?
You remember the good flora stuff that you can grow out in your own
guts?
Lets review the gut for gluten (gliadin) and other lectins.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20gluten+intestinal+permeability
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=VSL#3
Web for Vsl#3,
http://www.google.com/search?hl=en&lr=&q=vsl%233&btnG=Search
& adding keyword probiotic,
http://www.google.com/search?hl=en&lr=&q=vsl%233+probiotic&btnG=Search
>From the VsL#3 site,
http://www.vsl3.com/VSL3/about-vsl-works.asp
[...]
VSL#3® works by colonizing the GI tract with optimal quantities and
types of probiotic ("good") bacteria. These bacteria adhere to the
walls of the GI tract and form a barrier that protects the inner layer
of the gut from pathogenic ("bad") bacteria and other toxic
substances that can cause inflammation by modulating intestinal defense
mechanisms.
In addition, VSL#3® modulates a variety of substances that are
involved in the healing of inflammation. For example, VSL#3® has been
shown to induce the production of interleukin-10, an important
"chemical messenger" that suppresses inflammation. 22,35,39,49,64
Finally, evidence suggests that VSL#3® reduces intestinal permeability
by tightening up the junctions between the cells in the outer layer of
the intestine (the epithelium).39 If the spaces between the cells of
the gut wall become too large, bad bacteria and toxins can leak in,
causing inflammation.
<sniP>
Maybe we have another way to re-build good gut flora.
Anything you take that makes more IL-10 in the gut will help psoriasis.
So, I guess if you want to spend the big bucks. Be my guest and let us
know
how you poop!
But, wouldn't it be really elegant to cure P via a bug you implant up
your rectum?
Poetic justice for sure. The uP the butt cure for a craPPy disease. lol
--------------------------------------------------------------------------
--------------------------------------------------------------------------
Eat a worm (helminth) to clear your P! Now, just eat some wormy sugars?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16689863
Prevention of psoriasis-like lesions development in fsn/fsn mice by
helminth glycans.
Atochina O, Harn D.
Department of Immunology and Infectious Diseases, Harvard School of
Public Health, Boston, MA, USA.
The helminth glycan LNFPIII is an immunomodulatory molecule, driving
CD4(+) Th2-type biasing as well as immune suppression. Psoriasis is an
autoimmune disease where the immune mechanisms as well as the antigens
responsible for development of immune autoreactivity are still not
known. In the absence of defined immunological mechanisms, we asked
whether LNFPIII would function as novel therapy for psoriasis. We
tested the therapeutic efficacy of LNFPIII using the flaky skin
(fsn)/fsn mutant mouse model of psoriasis-like lesion development. We
found that treatment of mice with LNFPIII prevented the appearance of
psoriatic skin lesions on fsn/fsn mice. Examination of the skin 2 weeks
after treatment demonstrated that prevention of skin lesions was
associated with maintenance of normal epidermis thickness in
LNFPIII-treated mice as compared with a significantly thickened
epidermis in control treated and diseased mice. In addition, cells from
skin of LNFPIII-treated mice produced lower amounts of interferon-gamma
as compared with cells from skin of control treated diseased mice.
Examination of macrophages and T cells from peripheral lymph nodes of
control and LNFPIII-treated fsn/fsn mice showed that glycan treatment
reduced the numbers of Gr1(+)F4/80(+) macrophages and the numbers of
CD8(+) T cells, restoring the numbers of these two cell populations as
well as the CD4 : CD8 ratio to near normal levels. Overall, the results
from this study suggest that the helminth immunomodulatory glycan
LNFPIII functions to prevent development of psoriatic-like skin lesions
in fsn/fsn mice.
PMID: 16689863
Great!
The scientists at Harvard can stoP P in mice with worm sugar!
But don't we have another worm already?
http://groups.google.com/groups/search?q=cordyceps+psoriasis&qt_s=Search
(((((((((((((((((((((((((((((((((((((((((((((()))))))))))))))))))))))))))))))))))))))))))))))
Check this out. A new skin protein.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16689864
Influence of calcium on the proteolytic degradation of the
calmodulin-like skin protein (calmodulin-like protein 5) in psoriatic
epidermis.
Mehul B, Bernard D, Brouard M, Delattre C, Schmidt R.
Galderma R&D, Biot, France.
The calmodulin-like skin protein (CLSP) or so-called calmodulin-like
protein 5, a recently discovered skin-specific calcium-binding protein,
is closely related to keratinocyte differentiation. The 16-kDa protein
is proteolytically degraded in the upper layers of the stratum corneum
(SC) of healthy skin. With the use of specific new monoclonal
antibodies to CLSP, we were able to demonstrate that the abnormal
elevated levels of CLSP, characteristic of psoriatic epidermis, were
probably not due to an overexpression of the protein, but most likely
the result of its non-degradation. Further in vitro experiments using
recombinant CLSP and in situ data clearly showed that calcium protected
and chelator accelerated CLSP degradation. These data indicate that
CLSP degradation in the SC of psoriatic skin might be hindered by the
abnormally elevated calcium concentration. No degradation of CLSP in
psoriatic epidermis keeping its ability to bind protein as
transglutaminase 3 may have a physiological role in skin diseases such
as psoriasis.
PMID: 16689864
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20psoriasis+calmodulin
http://www.bmb.psu.edu/faculty/tan/lab/gallery/calmodulin.jpg
http://www.zoo.utoronto.ca/zoo344s/calmodulin.jpg
http://courses.washington.edu/conj/gprotein/calmodulin.htm
http://groups.google.com/groups/search?q=calmodulin+psoriasis&qt_s=Search
I guess we find it now,
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605183
randall... what does it do again?
randall
P news from around the world.
Can more NO stop the skin thinning of regular corticosteroids?
http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/05-16-2006/0004362384&EDATE=
[...]
NicOx and Ferrer initiated the research program focused on higher
potency agents following the encouraging clinical results from a
prototype
NO-donating corticosteroid, which suggested that NO donation may reduce
the
risk of dermal atrophy by maintaining blood flow in the skin.
Additionally,
the proposed role of NO in a number of biological processes in the skin
suggests that NicOx' technology could increase the efficacy and reduce
the
side effects of these agents.
NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-driven
biopharmaceutical company dedicated to the development of nitric oxide-
donating drugs to meet unmet medical needs. NicOx is targeting the
therapeutic areas of pain and inflammation and cardio-metabolic
disease.
Resources are focused on two lead compounds, HCT 3012, in phase 3
development for the treatment of osteoarthritis, and NCX 4016, in phase
2
for Peripheral Arterial Obstructive Disease (PAOD). NicOx has strategic
partnerships with some of the world's leading pharmaceutical companies,
including Pfizer Inc. and Merck and Co., Inc. NicOx S.A. is
headquartered
in Sophia-Antipolis, France, and is a public company listed on the
Eurolist
of Euronext Paris (segment: Next Economy).
<sniP>
----------------------------------
Would you be mindful of your P if it meant a four fold clearing?
http://www.mailtribune.com/archive/2006/0516/life/stories/mindful16.htm
[...]
How can mindfulness help against cancer and other diseases?
"If you've just gotten a diagnosis, most people hand it over to the
doctors. They don't do as well," says McMillan. "You do better if you
stay conscious of all that's happening. You feel in control and that
you have influence over it."
As for pain, being mindful and aware of breathing is a calming practice
that teaches you to be more accepting and compassionate with yourself,
Sheldon says.
Mindfulness-based stress reduction has been taught to prison inmates,
wardens, the Chicago Bulls and L.A. Lakers in championship seasons, and
has been made part of curricula in many law, business and medical
schools, according to writings of its creator, University of
Massachusetts Medical School's Jon Kabat-Zinn.
[...]
Clinical trials on the technique in the 1980s and 1990s by Kabat-Zinn
and others show a 41 percent drop in mortality for patients in cardiac
rehabilitation, increase in survival rates of melanoma and metastatic
breast cancer patients, significantly lowered glucose levels in type
one diabetes, improved functioning and fewer attacks in asthma
patients, a four-fold improvement in skin clearing with psoriasis and
improvement in symptoms of multiple sclerosis patients, according to
University of Massachusetts publications.
"What on earth is going on?" writes Kabat-Zinn. "You might say that we
are in the early stages of waking up as a culture to the potential of
interiority, to the power of cultivating awareness and an intimacy with
stillness and silence. We are beginning to realize the power of the
present moment to bring us greater clarity and insight, greater
emotional stability and wisdom. Meditation is no longer something
foreign and exotic to our culture. It is now as American as anything
else. It has arrived and none to soon, given the state of the world and
the huge forces impinging on our lives." <end>
Who is this Jon Kabat-Zinn guy?
http://www.powells.com/biblio/0786886544?&PID=25450
Let's find him,
http://www.umassmed.edu/behavmed/faculty/kabat-zinn.cfm
&
http://www.umassmed.edu/cfm/
This is so exciting I may need some NicOx...
Was that like nicotine and straight O2? lol
Maybe i have a yen for zen via zinn now?
Being mindful ain't bull. I'm concentrating on that itchy patch,
breathing
and letting it disolve itself with my mind's eye.....
Hey it ain't working or is it? ;-)
-----------------------------------
Does this story make sense?
http://www.prnewswire.co.uk/cgi/news/release?id=170972
[...]
Yet the British sun is just as dangerous as the sun in traditional hot
climate such as Southern France or Gambia. Every year in the UK, 7,000
people are diagnosed with skin cancer and 1,600 people die of malignant
melanoma - more than in Australia. <sniP>
Doesn't it seem like the folks downunder would be more likely to get
cancer?
__________________________________________________
>From Austrailia and New Zealand today.
http://www.pharmalive.com/News/index.cfm?articleid=341372&categoryid=10
NEW YORK--(BUSINESS WIRE)--May 16, 2006 - Bioenvision, Inc (NASDAQ:
BIVN) and Mayne Pharma Limited (ASX- MYP) today jointly announced that
they have entered into a Marketing and Distribution Agreement for the
innovative new cancer product, Evoltra(R) (clofarabine).
Under the agreement, Bioenvision granted Mayne Pharma exclusive rights
to market Evoltra(R) (clofarabine) for certain haematological
malignancies in Australia and New Zealand. Bioenvision will receive
milestone payments and a percentage of Mayne's net sales revenue. Mayne
Pharma is responsible for securing regulatory approval and government
reimbursement in Australia and New Zealand.
[...]
Bioenvision is also conducting late-stage preclinical development of
Evoltra(R) for the treatment of psoriasis and is planning further
worldwide development of Evoltra(R) in autoimmune diseases.
Evoltra(R) (clofarabine) is a next generation purine nucleoside analog.
<sniP>
----------------------------------------------------------------------------------
randall...
randall
We've had a fair share of fat posts recently. (see- cortisol a few
posts back)
This next one piggy backs all the rest. <grin>
Are HAMsters just like us?
So what you say? Well... if we have some hamster DNA who knows.
All the fat people in the world may have that FAT gene deleted some
how.
Then they can look like Cher or Fabio i suPPose. Or at least their kids
can.
http://www.medicalnewstoday.com/medicalnews.php?newsid=43089
Just Like Us, Social Stress Prompts Hamsters To Overeat, Gain Weight
Put a mouse or a rat under stress and what does it do? It stops eating.
Humans should be so lucky. When people suffer nontraumatic stress they
often head for the refrigerator, producing unhealthy extra pounds.
When Syrian hamsters, which are normally solitary, are placed in a
group-living situation, they also gain weight. So scientists at the
Center for Behavioral Neuroscience at Georgia State University are
using hamsters as a model for human stress-induced obesity. They want
to begin unraveling the complex factors that lead people to eat when
under stress and hope that the information can eventually be used to
block appetites under this common scenario.
The study, "Social defeat increases food intake, body mass, and
adiposity in Syrian hamsters," by Michelle T. Foster, Matia B. Solomon,
Kim L. Huhman and Timothy J. Bartness, Georgia State University,
Atlanta, appears in the May issue of the American Journal of
Physiology-Regulatory, Integrative and Comparative Physiology published
by The American Physiological Society.
Hamsters similar to humans
In the study, the researchers look at nontraumatic stress -- the stress
we experience in everyday life, such as getting stuck in traffic or
trying to complete a major project at work. It is distinct from
traumatic stress, such as suffering the death of a loved one. Traumatic
stress typically dulls the human appetite, said Bartness, the study's
senior researcher and an authority on obesity.
In the U.S., where food is plentiful and relatively cheap, overeating
can be difficult to control. Stress-related overeating is more
difficult to control than the overeating that people do just because
food tastes good and is available, Bartness said. If scientists could
learn how to reduce the urge to eat in the face of stress, it could
improve the health of a lot of people. And that was the point of this
study.
The researchers used Syrian hamsters, the kind commonly found in pet
stores. They set up a situation in which subordinate hamsters would
suffer a "social defeat" at the hands of a dominant hamster. The
researchers wanted to see if the defeated hamsters would eat more and
gain weight under the stress, just like a human. Mice and rats eat less
and lose weight when subjected to a similar stress, making them a poor
subject for human stress-induced obesity research.
The study asked three questions:
* Does repeated social defeat increase food intake, weight and fat in
hamsters?
* If so, how many defeats are necessary?
* Do intermittent (unpredictable) defeats increase fat and food intake
more than consecutive (predictable) defeats, as is true in humans?
An uncomfortable situation
To answer these questions, the researchers placed an 11-week-old
hamster (the subordinate intruder) into the cage of an older and larger
hamster (the dominant resident). The intruder remained in the
aggressor's cage for seven minutes per trial. The situation set up a
clear dominant versus subordinate situation between the hamsters, the
authors explained.
"Hamster aggression is highly ritualized, with dominance or submission
generally established within the first minute and maintained thereafter
through social signals and social communication between the opponents,"
the authors wrote. The intensity of most agonistic encounters was
moderate, with some chasing and biting, but with no actual tissue
damage.
A trained observer recorded submissive behaviors and also ensured that
no harm came to either of the hamsters, which normally live alone.
Because the smaller hamster was the intruder, the outcome of the
dominance/submissive tussle was a foregone conclusion.
The researchers found that, as a result of the stress of being placed
in the home cage of a larger resident, intruder hamsters subsequently:
* ate significantly more
* gained significantly more weight
* gained significantly more fat, including visceral fat
These results occurred when the intruder hamsters were placed in the
foreign cage as few as four times, a total of 28 minutes, over the
33-day experiment, Bartness explained. Hamsters that were placed in the
situation only once during the experiment did not eat more or gain
weight compared to a control group. In addition, the intruder hamsters
that were placed in the cage intermittently (at unpredictable times)
showed comparable weight and fat gain compared to those placed in a
foreign cage consecutively (at regular times).
However, while the intermittent group increased on all measures of fat
gain, the consecutive group increased on only two of the fat measures.
Still, this was an unexpected result.
"In humans, unpredictable [stress] events are more aversive than
predictable events, causing greater alterations in homeostasis and thus
increased stress," the authors wrote. "In addition, previous research
suggests that unpredictable events cause greater activation in brain
regions responsible for fear and anxiety in laboratory rats and
reduction in immune function compared with events that are
predictable."
Next steps
Syrian hamsters provide a good model for obesity research, not only
because they eat more and gain weight, but because, like humans, they
add fat to their abdomens -- visceral fat. Visceral fat is particularly
unhealthy because it affects the internal organs and is associated with
diabetes, cancer and other serious illnesses, Bartness said.
Bartness' team began a second study to determine whether other
stressors, such as a mild foot shock, produce the same effect as the
social defeat model; and whether the dominant hamsters gain weight and
fat as the result of the intrusion of the submissive hamsters.
Another line of inquiry would be to compare mice and rats to hamsters.
Humans and hamsters, which eat more under stress, share the same
predominant stress hormone, cortisol, noted Bartness, Rats and mice,
which eat less under stress, have a different primary stress hormone,
corticosterone. This raises the question of whether stress-induced
increases in cortisol play a more important role in the desire to eat
and weight gain compared to corticosterone.
Researchers will also want to know if drugs can block stress-induced
obesity, for example, by blocking the release of the stress hormone,
corticotrophin releasing factor (CRF), or by blocking the body's CRF
receptors, Bartness said. CRF, also sometimes referred to as
corticotrophin releasing hormone, produces the body's "fight or flight"
response under stress and helps kick off a cascade of physiological
responses.
"There are a whole suite of physiological responses that occur as a
result of stress," Bartness said. It will take time to unravel all
these physiological responses and to use that knowledge to block
stress-induced obesity. It may even turn out that the reactions are too
complex to easily block, he said.
###
Source and funding
"Social defeat increases food intake, body mass, and adiposity in
Syrian hamsters," by Michelle T. Foster, Dept. of Biology and Dept.
Psychology; Matia B. Solomon and Kim L. Huhman, Dept. of Psychology and
Center for Behavioral Neuroscience; and Timothy J. Bartness, Dept. of
Biology, Dept. of Psychology and Center for Behavioral Neuroscience,
Georgia State University, Atlanta, appears in the May issue of the
American Journal of Physiology-Regulatory, Integrative and Comparative
Physiology published by The American Physiological Society.
The research was funded by the National Institute of Diabetes and
Digestive and Kidney Diseases of the National Institutes of Health, the
National Institute of Mental Health and the National Science Foundation
Science and Technology Program.
The American Physiological Society was founded in 1887 to foster basic
and applied bioscience. The Bethesda, Maryland-based society has 10,500
members and publishes 14 peer-reviewed journals containing almost 4,000
articles annually.
APS provides a wide range of research, educational and career support
and programming to further the contributions of physiology to
understanding the mechanisms of diseased and healthy states. In May
2004, APS received the Presidential Award for Excellence in Science,
Mathematics and Engineering Mentoring (PAESMEM).
Contact: Christine Guilfoy
American Physiological Society
-----------------------------------------------------------------------------------------------------------
Big hit on the immune front.
IL-23 and P and cancer!
http://www.newscientist.com/article/dn9161.html
[...]
Tumours put up a protein "smokescreen" to escape the body¹s immune
system, and blocking those proteins helps kill cancer cells in mice, a
new study has found. The work also offers new insight into why some
inflammatory diseases increase a person¹s risk of cancer.
The immune-system protein that appears to help tumours escape attack is
called cytokine interleukin 23 (IL-23). High levels of IL-23 were found
in the human tumours studied by Martin Oft at the Schering-Plough
Institute in Palo Alto, California, US, and his colleagues. The team
also found that mice deficient in IL-23 did not develop as many tumours
as normal mice.
Under ordinary circumstances, IL-23 contributes to the recruitment of
cells known as neutrophils. These play an important role in the early
immune response to an infection, targeting foreign particles in the
body.
But the tough task of infiltrating diseased tissues and rooting out the
source of an illness belongs to another kind of immune cell called CD8
T-cells, Oft explains. And it is these cells that IL-23 appears to
repel. In the case of cancer, excess IL-23 prevents the CD8 T-cells
from
eliminating a tumour.
In one part of the experiment, mice received an antibody molecule that
blocks IL-23. These animals developed fewer tumours and eliminated
injected cancer cells more quickly than control mice. The researchers
think the antibody holds promise as a future tool to fight cancer in
humans, but they stress that it remains in the pre-clinical phase of
development.
The team's work also addresses the link between chronic inflammation
and
cancer, which doctors have suspected for more than a century. For
example. some inflammatory illnesses such as psoriasis and
inflammatory
bowl disease are associated with an increased cancer risk.
The team's work explains this link because earlier work has shown that
excess IL-23 in the body appears to drive chronic inflammatory disease.
****************************
IL-23 and P from the P newsgroup,
http://groups.google.com/groups/search?q=il-23+psoriasis&qt_s=Search
randall... Had my fourth meal of beets for lunch about one hour ago!
randall
Abstracts pertaining to P.
From, you guessed it, around the world.
More Psors1,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16702966
PSORS1: Linking Genetics and Immunology.
Elder JT.
1University of Michigan Medical Center, Department of Dermatology, Ann
Arbor, Michigan, USA.
Previous studies have localized the psoriasis susceptibility 1 (PSORS1)
locus to the proximal major histocompatibility complex class I region,
but approximately a dozen genes in the candidate region have thus far
been genetically inseparable. According to a team of researchers in the
United States and Germany, the primary genetic association has now been
worked out, implicating HLA-Cw6 "after all." The results integrate
genetics and immunology, further reinforcing our emerging understanding
of psoriasis.Journal of Investigative Dermatology (2006) 126,
1205-1206. doi:10.1038/sj.jid.5700357.
PMID: 16702966
Well this figures. I noticed IP3 right within the range of psors1 only
last week or so.
So we have psors1 thru 9,
http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?l177900
(where did eight go?) and psors1 has a dozen genes in it? It's no
wonder we don't have
a fix.
------------------------------------------------------------------------------------------------
This next one I can get a handle on.
Stuff that blunts LPS and TNF,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16702443
Discovery and Characterization of Triaminotriazine Aniline Amides as
Highly Selective p38 Kinase Inhibitors.
Lin TH, Metzger A, Diller DJ, Desai M, Henderson I, Ahmed G, Kimble EF,
Quadros E, Webb ML.
Pharmacopeia Drug Discovery, Inc.
The p38 MAP kinases are a family of serine/threonine protein kinases
that play important roles in cellular responses to inflammation and
external stress. Inhibitors of the p38 MAP kinase have shown promise
for potential treatment of inflammatory disorders such as rheumatoid
arthritis, acute coronary syndrome, psoriasis and Crohn's disease. We
identified a novel class of p38 inhibitors via high throughput
screening. PS200981, a representative compound identified from
screening a collection of combinatorial libraries, amounting to 2.1
million compounds, inhibits p38alpha kinase and the LPS-induced
increase in TNFalphalevels in THP-1 cell media with IC50 values 1
microM. The screening data revealed a preferred synthon,
3-amino-4-methyl benzamide which is critical for the activity against
p38. This synthon appeared almost exclusively in screening hits
including PS200981, and slight variations of this synthon including
3-amino benzamide and 2-amino-4-methyl benzamide also contained in the
library were inactive. PS200981 is equally potent against the alpha and
beta forms of p38 but did not inhibit p38gamma and is > 25-fold
selective versus a panel of other kinases. PS200981 inhibited the
LPS-induced increase in TNFalphalevels when administered at 30 mg/kg to
mice. Selectivity and in vivo activity of this class of p38 inhibitors
was further demonstrated by PS166276, a highly structurally related but
more potent and less cytotoxic inhibitor, in several intracellular
signaling assays, and in LPS challenged mice. Overall, this novel class
of p38 inhibitors is potent, active in vitro and in vivo, and is highly
selective.
PMID: 16702443
I ran a web search of PS200981 and actually had two hits. One in French
and
english but no info on it.
--------------------------------------------------------------------------------------------------
More Strep Th1 stuff from Mexico,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16700789
Peripheral blood mononuclear cells proliferation and Th1/Th2 cytokine
production in response to streptococcal M protein in psoriatic
patients.
Perez-Lorenzo R, Nunez-Oreza LA, Garma-Quen PM, Lopez-Pacheco E,
Bricaire-Bricaire G.
>From the Centro de Investigaciones en Enfermedades Tropicales,
Universidad Autonoma de Campeche, Mexico, Facultad de Ciencias Quimico
Biologicas, Universidad Autonoma de Campeche, Hospital General de Zona
no. 1. IMSS, Campeche, Mexico.
Abstract Background Psoriasis is a chronic skin disease that is
probably a T cell-mediated autoimmune condition which is strongly
associated with streptococcal throat infections. Although some groups
have associated the involved response with different streptococcal
antigens, M protein has been described as the major virulence factor of
Streptococcus pyogenes. Thus, it is necessary to describe some features
of the cellular responses to this streptococcal antigen. Methods
Proliferation and Th1/Th2 cytokine production of peripheral blood
mononuclear cells (PBMC) in response to total soluble extracts from
type M5 S. pyogenes with (TSE37Sp) and without (M(-)TSESp) M protein
were analyzed in 10 psoriatic patients and 10 healthy controls. Results
PBMC from both patients and controls proliferated to both extracts.
Responses to M(-)TSESp were significantly lower than those to TSE37Sp
(P < 0.05). PBMC IL-2 and gammaIFN production after TSE37Sp stimulus
was much higher than after M(-)TSESp antigenic stimulation in both
groups (P < 0.05). Meanwhile, IL-4 production was quite low in both
groups and in response to both extracts. We found a differential
production of IL-10 between groups. PBMC from healthy controls
responded to TSE37Sp with a much higher production of this cytokine as
compared to the responses showed to M(-)TSESp while the cells from
psoriatic patients responded without differences in the production of
IL-10. Conclusion Results obtained suggest an important Th1 response to
M protein in psoriatic patients which could be associated with the
cellular responses involved in psoriasis, while healthy subjects
respond in a probably non-Th2 IL-10 producing regulatory T cells
fashion.
PMID: 16700789
----------------------------------------------------------------------------------------------------
This one smells familiar! Is this an advitech (dermylex) study?
Safety and Efficacy of a Milk-derived Extract in the Treatment of
Plaque Psoriasis:An Open-label Study.
Poulin Y, Pouliot Y, Lamiot E, Aattouri N, Gauthier SF.
Centre de Recherche Dermatologique du Quebec metropolitain (CRDQ),
Quebec, Canada, pouli...@videotron.ca.
PMID: 16699908
Sure looks like dermylex,
http://groups.google.com/groups/search?q=advitech&qt_s=Search
--------------------------------------------------
MT203, a new mab to nab P?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16697465
A human monoclonal IgG1 potently neutralizing the pro-inflammatory
cytokine GM-CSF.
Krinner EM, Raum T, Petsch S, Bruckmaier S, Schuster I, Petersen L,
Cierpka R, Abebe D, Molhoj M, Wolf A, Sorensen P, Locher M, Baeuerle
PA, Hepp J.
Micromet AG, Staffelseestr. 2, D 81477 Munich, Germany.
The pro-inflammatory cytokine GM-CSF is aberrantly produced in many
autoimmune and chronic inflammatory human diseases. GM-CSF
neutralization by antibodies has been shown to have a profound
therapeutic effect in animal models of rheumatoid arthritis,
inflammatory lung diseases, psoriasis and multiple sclerosis. Moreover,
the absence of GM-CSF in null mutant mice ameliorates or prevents
certain of these diseases. Here we describe the biophysical and
biological properties of a human anti-GM-CSF IgG1 antibody designated
MT203, which was derived by phage display guided selection. MT203 bound
with picomolar affinity to an epitope on human and macaque GM-CSF
involved in high-affinity receptor interaction. As a consequence, the
antibody potently prevented both GM-CSF-induced proliferation of TF-1
cells with a sub-nanomolar IC50 value and the production of the
chemokine IL-8 by U937 cells. MT203 neutralized equally well
recombinant (r) human (h) GM-CSF from Escherichia coli and yeast, and
also normally glycosylated GM-CSF secreted by human lung epithelial
cells in response to IL-1beta stimulation. Furthermore, MT203
significantly reduced both survival and activation of peripheral human
eosinophils as may be required for effective treatment of inflammatory
lung diseases. The antibody did not show a detectable loss of
neutralizing activity after 5 days in human serum at 37 degrees C.
Based on its favorable properties, MT203 has been selected for
development as a novel anti-inflammatory human monoclonal antibody with
therapeutic potential in a multitude of human autoimmune and
inflammatory diseases.
PMID: 16697465
-------------------------------------------------------------------
This one is timely. I posted the big calcium post for Manfred just 14
hr's ago.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16689864
Influence of calcium on the proteolytic degradation of the
calmodulin-like skin protein (calmodulin-like protein 5) in psoriatic
epidermis.
Mehul B, Bernard D, Brouard M, Delattre C, Schmidt R.
Galderma R&D, Biot, France.
The calmodulin-like skin protein (CLSP) or so-called calmodulin-like
protein 5, a recently discovered skin-specific calcium-binding protein,
is closely related to keratinocyte differentiation. The 16-kDa protein
is proteolytically degraded in the upper layers of the stratum corneum
(SC) of healthy skin. With the use of specific new monoclonal
antibodies to CLSP, we were able to demonstrate that the abnormal
elevated levels of CLSP, characteristic of psoriatic epidermis, were
probably not due to an overexpression of the protein, but most likely
the result of its non-degradation. Further in vitro experiments using
recombinant CLSP and in situ data clearly showed that calcium protected
and chelator accelerated CLSP degradation. These data indicate that
CLSP degradation in the SC of psoriatic skin might be hindered by the
abnormally elevated calcium concentration. No degradation of CLSP in
psoriatic epidermis keeping its ability to bind protein as
transglutaminase 3 may have a physiological role in skin diseases such
as psoriasis.
PMID: 16689864
---------------------------------------------------------------------------------
Anymore studies like these and someone may even figure out a cure this
decade.
randall.... if they can make a $ on it!
randall
P News from around the world.
Support the UK skin walk,
http://news.scotsman.com/health.cfm?id=751802006
And now current abstracts from around the world.
The Germans are looking at the Tonsills,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16709873
Identical TCR beta-Chain Rearrangements in Streptococcal Angina and
Skin Lesions of Patients with Psoriasis Vulgaris.
Diluvio L, Vollmer S, Besgen P, Ellwart JW, Chimenti S, Prinz JC.
Department of Dermatology, Ludwig-Maximilians-University of Munich,
Munich, Germany;
Tonsillar infection with Streptococcus pyogenes may induce several
nonsuppurative autoimmune sequelae. The precise pathogenetic mechanisms
behind this clinically well-established association are still
unresolved. Using TCR analysis, we sought to identify a link between
streptococcal tonsillitis and the T cell-mediated autoimmune response
in psoriasis. Three patients with streptococcal-induced psoriasis
underwent tonsillectomy. Using size spectratyping and sequencing of TCR
beta-chain variable region gene (TCRBV) rearrangements, we compared the
TCR usage of psoriatic skin lesions, blood, tonsils, and tonsillar T
cells fractionated according to the expression of the skin addressin
"cutaneous lymphocyte-associated Ag" (CLA). TCRBV-size spectratype
analysis of the blood lymphocytes, tonsils, and the CLA-negative
tonsillar T cells revealed largely unselected T cell populations.
Instead, TCRBV gene families of the psoriatic lesions and skin-homing
CLA-positive tonsillar T cells displayed highly restricted
spectratypes. Sequencing of TCRBV cDNA identified various clonal TCRBV
rearrangements within the psoriatic lesions that indicated Ag-driven T
cell expansion. Several of these clonotypes were also detected within
the tonsils and, in one of the patients, within the small subset of
CLA-positive tonsillar T cells, suggesting that T cells from the same T
cell clones were simultaneously present within skin and tonsillar
tissue. Because after tonsillectomy psoriasis cleared in all three
patients our observations indicate that T cells may connect psoriatic
inflammation to streptococcal angina. They suggest that the chronic
streptococcal immune stimulus within the tonsils could act as a source
for pathogenic T cells in poststreptococcal disorders, and they may
help to explain why eliminating this source with tonsillectomy may
improve streptococcal-induced sequelae.
PMID: 16709873
These German dudes going back to the begining are on to something!
Could this
be an IMID moment?
----------------------------------------------------------------------------------------------------
Do you ever think of this group as a Psycho ward?
Maybe we should? lol
>From Norway today,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16709492
Coping with exacerbation in psoriasis and eczema prior to admission in
a dermatological ward.
Wahl AK, Mork C, Hanestad BR, Helland S.
Department of Public Health and Primary Health Care, University of
Bergen. Astri...@isf.uib.no.
Chronic dermatologic diseases, such as psoriasis and eczema, may cause
significant psycho-social problems and stress. Our objectives were to
characterize how hospitalised patients coped with psoriasis and eczema,
and to investigate the relationship between coping and quality of life.
Data are based on survey forms completed upon admission to the
dermatology ward from 212 patients with chronic dermatological
diseases, 146 with psoriasis and 66 with eczema. 108 were men, average
age 48 years. The Norwegian versions of the standardized survey
questionnaires, Jalowiec Coping Scale and Dermatological Life Quality
Index, were used to evaluate coping and quality of life. We found that
optimism, belief-in-oneself and confrontational coping strategies were
most frequently used. Long duration of the disease was correlated to
the belief-in-oneself strategy, while short duration was related to
supportive strategies. More frequent use of confrontational and
optimistic modes was significantly related to better quality of life.
More frequent use of emotional and evasive modes was significantly
related to poorer quality of life. There was no significant difference
between the psoriasis and eczema groups in terms of use of coping
strategies, with exception of emotional strategies. Knowledge of coping
strategies and quality of life among patients with chronic
dermatological diseases is important for improvement in health services
for these patients.
PMID: 16709492
P is an IMID. How many IMIDs are there?
Who cares?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16709321
Co-occurrence and comorbidities in patients with immune-mediated
inflammatory disorders: an exploration using US healthcare claims data,
2001-2002.
Robinson D Jr, Hackett M, Wong J, Kimball AB, Cohen R, Bala M; The IMID
Study Group.
MSPH, Centocor, Inc., Malvern, PA, USA.
OBJECTIVE: Research in immune-mediated inflammatory disorders (IMIDs)
suggests that several diseases share disruptions in key cytokines. A
common pathogenesis may present as similar patterns of disease
co-occurrence and comorbidity, which could be observed through the
analysis of healthcare claims datasets.METHODS: Adult patients
continuously enrolled from 2001-2002 were identified in two US
healthcare datasets containing medical and drug claims from health
plans and self-insured employers. Patients with treatment records
indicating an IMID were selected (e.g., rheumatoid arthritis,
psoriasis, Crohn's disease); controls for each disorder were matched
3:1 based on age, gender, region, and previous insurance coverage. IMID
cohorts and comorbidities were identified using International
Classification of Diseases, 9th revision codes. Prevalence relative
risk was used to assess co-occurrence and comorbidity rates in IMID
cohorts and controls. Medical and drug utilization patterns were also
explored.RESULTS: Findings were similar across the two datasets. IMID
patients represented about 4% of the population; specific IMID
prevalence matched the epidemiology literature. Patients with at least
one IMID had a higher risk for another IMID when compared to controls.
The risk for infectious, renal, liver, and ulcerative comorbidities was
also elevated. Selected drug utilization patterns confirmed comorbidity
findings. IMID patients used more healthcare resources compared to
controls; findings were robust under sensitivity analyses.CONCLUSIONS:
IMID patients were generally more likely than controls to have another
IMID, supporting the concept that the diseases are related. These
patients also had higher comorbidity rates. Findings may be limited by
the nature of claims datasets and the confounding effect of current
treatments. Prospective studies are needed to determine whether IMIDs
have a common pathogenesis.
PMID: 16709321
When is uncle sam gonna bust out the big bucks to do this research? The
NIH should
be helping people by getting to the bottom of these IMIDs. I don't have
another
IMID, but if i did i'd feel like a squid. Let's face it, one imid is
enough. Any more
and your screwed beyond rePair.
Damn IMIDs!
randall ... having an IMID moment. One's enough. Now turn it OFF!
JXStern
On 20 May 2006 11:29:02 -0700, "randall" <ranh...@aol.com> wrote:
>OBJECTIVE: Research in immune-mediated inflammatory disorders (IMIDs)
>suggests that several diseases share disruptions in key cytokines. A
>common pathogenesis may present as similar patterns of disease
>co-occurrence and comorbidity, which could be observed through the
>analysis of healthcare claims datasets.
Yeah, except something like that would be obvious to every medical
practitioner for the past 10,000 years, and it ain't the case.
> IMID patients used more healthcare resources compared to
>controls;
Doh!
Match Hummer drivers to average drivers and guess what, Hummer drivers
use more gasoline compared to controls!
You tax dollars at work.
J.
randall
JXStern wrote:
> was: P news
> On 20 May 2006 11:29:02 -0700, "randall" <ranh...@aol.com> wrote:
>
> >OBJECTIVE: Research in immune-mediated inflammatory disorders (IMIDs)
> >suggests that several diseases share disruptions in key cytokines. A
> >common pathogenesis may present as similar patterns of disease
> >co-occurrence and comorbidity, which could be observed through the
> >analysis of healthcare claims datasets.
>
> Yeah, except something like that would be obvious to every medical
> practitioner for the past 10,000 years, and it ain't the case.
2,000 years ago religious leaders called psoriasis sapachat.
And that isn't a term for bummer genes! Yet, in their defense
it may have prevented the expansion of those genes.
Surely some in that time period may have noticed things they couldn't
explain precisely. With computers, uPdated testing and current
vernacular
we can make concise scientific comparisons. Hardly would
many have the ability to compare all the Th1/Th2 cytokines untill
now and present them in a fashion that would reveal trends and
underlaying pathways that give rise to those that are still unknown.
Take atopic dermatitis in comparison to psoriasis.
While the former is a Th2 IMID set, the latter is Th1. But
comparing exact order or progression gives greater understanding
to the whole of immunology. And will elucidate Th2 cancer conditions
in the process.
As to the former.
The role of microorganisms in atopic dermatitis.
Baker BS.
Atopic dermatitis (AD) is a common, fluctuating skin disease that is
often associated with atopic conditions such as asthma and IgE-mediated
food allergy and whose skin lesions are characterized by a Th-2
cell-mediated response to environmental antigens. The increasing
prevalence and severity of atopic diseases including AD over the last
three decades has been attributed to decreased exposure to
microorganisms during early life, which may result in an altered
Th-1/Th-2-balance and/or reduced T cell regulation of the immune
response. Patients with AD exhibit defects in innate and acquired
immune responses resulting in a heightened susceptibility to bacterial,
fungal and viral infections, most notably colonization by S. aureus.
Toxins produced by S. aureus exacerbate disease activity by both the
induction of toxin-specific IgE and the activation of various cell
types including Th-2 cells, eosinophils and keratinocytes. Allergens
expressed by the yeast Malazessia furfur, a component of normal skin
flora, have also been implicated in disease pathogenesis in a subset of
AD patients. Microorganisms play an influential role in AD
pathogenesis, interacting with disease susceptibility genes to cause
initiation and/or exacerbation of disease activity.
PMID: 16542358
Recent developments in the immunology and biology of Malassezia
species.
Ruth Ashbee H.
Skin Research Centre, Institute of Molecular and Cellular Biology,
Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Malassezia spp. are members of the normal cutaneous flora, but are also
associated with several cutaneous diseases. Recent studies of the
interaction of Malassezia spp. with melanocytes, fibroblasts,
keratinocytes and dendritic cells have highlighted their potential to
modulate the immune response directed against them. In normal skin they
may downregulate the inflammatory response, allowing them to live as
commensals. In contrast, in atopic/eczema dermatitis syndrome and
psoriasis, they may elicit an inflammatory response that contributes to
the maintenance of lesions. Future research may define ways to
influence this inflammatory cycle and hence to control or prevent
exacerbations of these diseases.
PMID: 16706784
Experts in each IMID need another one to co-ordinate similarities as
well
as differences. Untill everything is explained about each IMID
the genetics that lead to the proteins will remain elusive but not
UNknown.
>
> > IMID patients used more healthcare resources compared to
> >controls;
>
> Doh!
>
> Match Hummer drivers to average drivers and guess what, Hummer drivers
> use more gasoline compared to controls.
While we all don't drive hummers it's not like the reverse isn't true
for those
so selected.
And the fact that we all have immune systems doesn't mean that
a few percent may have not continuous problems skewing one towards
IMID pathways that are only now being completely understood.
So, you and I know that many folks still view us as sapachat!
The truth may set them free and the cure us.
>
> You tax dollars at work.
Isn't that the problem? The cytokines and dollars aren't being utilized
to their full potential?
If we can get both on track, maybe we won't have to be the funky
hummer freaks on the fringe, so to speak. And the stuPid freaks
who look at us with saPachat eyes will wake uP when they
get the big C (cancer) and realize someone somewhere should
have spent a few more bucks on understanding Th1 and Th2
(cancer) conditions. Aka- IMIDs.
And upon further reflection today, I do have two IMIDs. I forgot about
my PsA. Only since i've been doing the IP6 trial has it come back to
the point that i consider it a nuisance.
randall... sheesh, a little hummer while driving down the road can't
hurt!
>
> J.
randall
What's toPical for the umPteenth time? Is it P or a
bug in your lower guts?
These gut folks in the next link are starting to suck it uP!
Their rat exPeriments are honing in on imPortant
data.
Stress makes your gut walls leaky!
Time to plug those gaPPing HOLES?
Straight from the GosPel according to Leaky Brains.
They may find the ultimate truth one day. Today ain't it.
Unless their reading this. lol
http://www.sciencenews.org/articles/20060520/food.asp
Bacteria Can Keep Their Kin in Check
Ben Harder
Our intestines contain a metropolis of living, thriving bacteria. About
500 species crowd into the large intestine's unique ecosystem, for
example. Most of them are harmless to us-most of the time. But even
these ordinarily benign, or commensal, bacteria may contribute to
certain bowel disorders, past research has suggested.
Now, scientists have evidence that the mammalian gut can be fortified
to resist the occasional disruptions of resident microbes. To keep
bacteria in check, Mary H. Perdue of McMaster University in Hamilton,
Ontario, and her colleagues fed laboratory rats a special dietary
supplement.
Its key ingredient? Yet more bacteria.
Such beneficial bugs, called probiotics, are the focus of a booming
field of medical research. Findings suggest that certain bacterial
strains can guard the body against a variety of ills. (For examples,
see "Flora Horror," "Germs That Do a Body Good," and "Spray Guards
Chicks from Infections.")
In the new study, Perdue's team used commercially available strains of
Lactobacillus helveticus and Lactobacillus rhamnosus that are sold
together in powder form. The researchers dissolved the powder in water
and made sure the organisms were alive.
Then, for 17 days, the team gave the mixture to some lab rats and
sterile drinking water to others. Both groups of animals ate normal
lab-rat chow throughout the experiment. A week into that regimen, the
researchers began subjecting the rats to what rodent researchers call
water-avoidance stress.
They placed each animal on a small platform in the middle of a small
pool. The animals weren't in danger of drowning, but during each
hour-long test they also couldn't leap to dry land from their island of
safety.
"Rodents have a natural aversion to water, and they become very anxious
if they can't escape," Perdue says. The water-avoidance exercise, she
says, "is a purely psychological stressor."
The rats experienced the stressful test each day for the final 10 days
of the experiment.
Stress and sickness
Psychological stress can have negative effects on people's intestinal
health. Stress has been linked to irritable bowel syndrome and symptoms
of Crohn's disease. Long-term stress is also associated with relapses
of ulcerative colitis, an inflammatory bowel disorder.
Perdue says that stress encourages commensal bacteria to adhere to the
intestinal wall and alters the wall's permeability, making it "leaky."
When bacteria slip out of the gut and reach other tissues, the body may
overreact with a damaging inflammatory response.
Perdue's team designed its study to probe whether probiotics might
bolster the gut's protection against the effects of stress. After
giving the rats the probiotic mixture or plain water for 17 days, the
researchers inspected the animals' guts.
In animals that had drunk plain water, about 100 bacteria clung to each
square millimeter of the tissue's inner walls. By comparison, in rats
that had received probiotics, two portions of the intestines had 14 and
21 bacteria, on average, per square millimeter, the researchers report
in an upcoming Gut.
Rats that hadn't been subjected to stress had no bacteria adhering to
their intestinal walls, the researchers report.
Perdue and her colleagues also removed and dissected lymph nodes to
which gut-escaping bacteria tend to migrate. Animals that had received
the probiotics before and during the period of chronic stress had no
bacteria in the targeted lymph nodes. By contrast, the corresponding
nodes from other animals contained an average of more than 1,000 germs.
"The probiotic bacteria that we gave the animals completely prevented
the penetration of commensal bacteria through the intestinal wall,"
Perdue reports. "The probiotics appear to be forming a protective layer
over the surface of the intestine."
"The probiotics are protecting the intestine from the dysfunction that
arises from stress," agrees gastroenterologist Michael Camilleri of the
Mayo Clinic in Rochester, Minn.
But the coating effect that Perdue describes may not be the main
contributor to the reduction in bacterial escape, Camilleri adds.
Rather, probiotics may increase intestinal cells' production of mucus
or of immune-system proteins called immunoglobulins, he says.
Data from the study indicate that stressed animals' intestines remain
leaky regardless of whether the animals receive probiotics, he notes.
Further research will be needed to explain the apparent discrepancy
between that fact and the protective effect of the probiotics, he says.
The research has potential clinical applications in inflammatory
disorders such as Crohn's disease and pouchitis, which can be a
complication of Crohn's or ulcerative colitis, Camilleri says.
"There is increasing evidence of a minor inflammatory state in
irritable bowel syndrome," he says, so probiotics might make a
difference in that condition, too.
"We don't want to make too big a jump," Perdue cautions. "But it's
certainly possible" that probiotics might help people with irritable
bowel syndrome.
Products that claim to contain probiotics are widely available, but
Perdue offers some caveats.
"Most of them have not been tested in a scientific manner. And a lot of
them probably don't do anything because the bacteria might be dead or
might not be present in sufficient numbers," she says.
On the other hand, she adds, "probiotics don't do any harm."
Eventually, she predicts, "we'll have different mixtures of probiotics
to treat different conditions."
References:
Harder, B. 2006. Flora horror. Science News 169(Feb. 18):104-105.
Available at http://www.sciencenews.org/articles/20060218/bob8.asp.
______. 2002. Germs that do a body good. Science News 161(Feb.
2):72-73. Available at
http://www.sciencenews.org/articles/20020202/bob9.asp.
Raloff, J. 1998. Spray guards chicks from infections. Science News
153(March 28):196. Available at
http://www.sciencenews.org/pages/sn_arc98/3_28_98/fob1.htm.
Zareie, M., . . . M.H. Perdue. In press. Probiotics prevent bacterial
translocation and improve intestinal barrier function in rats following
chronic psychological stress. Gut. Abstract available at
http://www.f1000medicine.com/pubmed/16638791.
Further Readings:
Harder, B. 2003. Bacteria-stocked beverage clears pathogens from nose.
Science News Online (March 1). Available at
http://www.sciencenews.org/articles/20030301/food.asp.
Mary H. Perdue, McMaster University, has a Web page at
http://www.fhs.mcmaster.ca/idrp/perdue.htm.
Sources:
Michael Camilleri
Mayo Clinic College of Medicine
Mayo Clinic
Rochester, MN 55905
Mary H. Perdue
McMaster University
Faculty of Health Sciences
1200 Main Street, West
Hamilton, ON L8N 3Z5
Canada
---------------------------------------------------------------
What a crack uP! These folks are light years behind David Webster
and his Wit Kit plus proflora treatments. Still... there trying to
catch uP.
When will the hundreth monkey finally get the ball rolling?
We need some gravity out there. Anyone heP?
-------------------------------------------------
Can mom's breastmilk be front loaded with IL-10 to pre-program your
Immune system?
Yes!
http://www.health24.com/dietnfood/Probiotics/15-1940,28395.asp
Reuteri boosts infant immunity
An interim report from the Karolinska Institute's Centre for Allergy
Research has revealed that expectant and nursing mothers taking the
probiotic strain Lactobacillus reuteri ATCC 55730 (Reuteri) appear to
have higher levels of anti-inflammatory molecules in their breast milk,
which could offer their babies better protection against allergies and
other diseases.
Anti-inflammatory agents increased
In 2001 the Swedish medical research team launched the clinical study
with over 200 moms and newborn infants to demonstrate that children
receiving probiotic supplements, good bacteria that support and promote
a healthy digestive system, are less likely to develop allergies
compared to children in a control group.
Half of the mothers received Reuteri supplements for four weeks prior
to the birth of their babies and their infants then received Reuteri
supplements for the next twelve months. An analysis of breast milk
taken from the mothers in the supplement group within days of giving
birth found increased levels of the anti-inflammatory cytokine (cell
signal substance) IL-10 and reduced levels of TGF-beta-2.
Direct effect on child immunity
Professor Bengt Bj?rkst?n, who is leading the study at the
Karolinska Institute, says the increased levels of IL-10 combined with
reduced levels of TGF-beta-2 in the milk of mothers receiving Reuteri
could suggest a direct effect on child immunity.
According to Bj?rkst?n, IL-10 is key to the regulation of the
immune system and has been shown to have anti-flammatory properties.
These findings are consistent with less inflammation in the breasts of
mothers taking Reuteri and an increased supply of the key cytokine
IL-10 to the infant.
"To find this increase in mother's milk after a relatively short period
of supplementation is extremely positive. This presents an opportunity
to develop probiotics for use by expectant and nursing mothers to
improve both their own health and that of their babies," says
Bj?rkst?n.
Reuteri meets strict criteria
According to Cape Town paediatrician Dr Deon Smith, Reuteri is the only
probiotic available in South Africa that meets the strict criteria that
define a probiotic and is often prescribed for the treatment of
infectious diarrhoea, antibiotic-associated diarrhoea and the treatment
of yeast infections.
The probiotic strain Reuteri was first isolated in breast milk and has
since been cultivated. The final results of the study are expected in
2005. ? (Health24)
Read more:
Immunity boosters: Pre- and Probiotics
http://www.health24.com/dietnfood/You_are_what_you_eat/15-49-776,16776.asp
Check their list of factors that lower immunity.
Notice anything missing?
((((((((((((((((((((((((((((((((((((((*+*)))))))))))))))))))))))))))))))))))))
The one rather substantial fact none of these articles tell you. Or
possibly
they simply don't know, IS THAT YOU CAN BREASTFEED YOUR COLON
NOW.. You don't need to be a new born to be reborn with a
colon-i-zation.
OLD folk can have young guts again. WiPe those mortal zens off your
soul. lol
You can come in from the other end and put those good bacteria (wit
kit)
into a Pre-prepared colon to re-grow a 80::20 ratio of Lacti loving
bacteria in the next 30 days. No more alkaline leaky colons. The
good flora turns the colon back into a slightly acidic IL-10 pumping
immune normalizing machine....
Story ended. P ended. Sweet dreams... nightmare over...
Or you can use some pharma glue to block a downsteam cytokine like TNF
for about $20K a year. Doesn't stoP the cause and guarantee's
your local pharmacy and drug producer's an unlimited income.
A scam on the insurer's and those that pay premiums.
And btw have you figured out the answer to the question above?
((((*&*))))
It's alcohol that screws the good flora.
Doesn't the OTC western liquid pressue pill makes us look weak to those
in other cultures?
http://islam.about.com/od/health/f/alcohol.htm
Do we have the guts left to do the right thing?
Time will tell!
randall.... it's ben harder for some to learn!
randall
P News from around the world.
16 year old psoriatic murdered in China
http://news.xinhuanet.com/english/2006-05/21/content_4580442.htm
Phony doctor arrested for poisoning 16-year-old girl to death
www.chinaview.cn 2006-05-21 22:22:22
HOHHOT, May 21 (Xinhua) -- A fraudster, posing as a qualified
doctor, has been arrested after his so-called "secret recipe" poisoned
a 16-year-old girl to death in north China's Inner Mongolia Autonomous
Region, a local police source said.
Suspect Bai Mingsheng, prescribed 32 sets of homemade medicines for
Zhang Jialing, a girl in Ulanqab City who suffered from psoriasis, an
inflammatory skin disease characterized by recurringred patches, in
February, the girl's father Zhang Peijun said.
After taking all the medicines, Zhang fell into shock and was sent
to a local hospital for emergency treatment on March 23, but she died
the next day from drug poisoning, Zhang's father said.
Bai admitted that the medicine contained the poisonous drug
hydrargyrum. An examination of Zhang's body confirmed that she died of
chronic poisoning from the hydrargyrum. Enditem
Editor: Luan Shanglin
What is the poinous drug hydragyrum?
I'm game, lets google.
OH!
http://chemistry.about.com/od/alchemicalsymbols/a/alchemyhg.htm
Mercury or Hydrargyrum
>From Anne Marie Helmenstine, Ph.D.,
Your Guide to Chemistry.
Alchemy Symbol
Mercury has also been known as quicksilver and hydrargyrum. The symbol
for the metal mercury was sometimes the same as the astrological symbol
for the planet Mercury. The element could be represented by a stylized
snake or serpent. Alchemists would heat elemental mercury with nitric
acid to prepare mercuric oxide. The reaction produced a thick red vapor
which hovered over the surface of the solution, while the mercuric
oxide precipitated and fell to the bottom of the liquid in the form of
bright red crystals. Mercury was believed to transcend the liquid and
solid states. The belief carried over into other areas, as mercury was
thought to transcend life/death and heaven/earth.
------------------------------------------
Lets find it in pubmed for China!
[An autopsy analysis on 14 cases of poisoning death caused by illegal
quackery]
[Article in Chinese]
Chen L, Huang G.
Faculty of Forensic Medicine, Tongji Medical University, Wuhan.
In this paper, 14 cases on poisoning death caused by illegal quackery
were analyzed. The results indicated that the causes and routes of
poisoning were various, and that there were three kinds of poisoning
types in illegal quackery. Main points of forensic identification were
pointed out. In addition, some medical and administrative measures and
possible measures were also investigated. The authors suggest that
measures as above are of great importance for preventing similar
poisoning and improving forensic identification.
PMID: 10375837
__________________________________________________
Just terrible.
Moving on.
Laser beams for the skin.
http://www.oregonlive.com/news/oregonian/index.ssf?/base/news/1147895760104250.xml&coll=7
___________________________________________
I wonder when people are gonna bite the bullet and clean
up their gullets?
WeLL that would be the opposite end of that proposition and the
middle areas and any funky stomach bugs.. and
Wait. I did the gut thing last night.
randall... life is a circle, uroborically sPeaking.
randall
P News from around the world.
http://boston.bizjournals.com/boston/stories/2006/05/22/daily45.html
Synta launches human trials for anti-inflammatory drug
Synta Pharmaceuticals Corp. has launched two new midstage human
clinical trials to test an anti-inflammatory drug.
The Lexington, Mass.-based private company said it had began dosing
patients in two separate Phase II trials regarding the compound
apilimod mesylate. On trial will focus on rheumatoid arthritis and the
other will target common variable immunodeficiency, a condition that
can lead to gastrointestinal complications.
Apilimod mesylate is designed to inhibit a family of proteins that
cause inflammations in conditions including Crohn's disease, psoriasis,
rheumatoid arthritis, multiple sclerosis and gastrointestinal problems
from common variable immunodeficiency.
Synta is also developing drugs to treat cancer.
_____________________________________
More synta and P.
http://www.pharmalive.com/News/index.cfm?articleid=343772&categoryid=21
[...]
"We are very enthusiastic about the clinical potential of apilimod
mesylate, the first oral inhibitor of IL-12 and IL-23, in RA and CVID,"
said Eric Jacobson MD, vice president & chief medical officer of Synta.
"As a rheumatologist, I believe that many RA patients would prefer an
oral small-molecule, disease-modifying agent for their disease over
injectable protein-based treatments. RA is a devastating chronic
disease that affects five million patients globally and three million
patients in the US. Patients suffering from CVID also have unmet
medical needs since there are no approved therapies for the GI
manifestations of this serious orphan condition."
About Apilimod Mesylate (STA-5326)
Apilimod mesylate is a novel, oral small-molecule compound that
selectively inhibits the production of the IL-12 family of proteins,
key cytokines in the inflammatory pathway. The IL-12 cytokine family
(including IL-12 and IL-23) is the master regulator of the TH1 pathway,
which drives major chronic inflammatory diseases, including Crohn's
disease, psoriasis, rheumatoid arthritis, multiple sclerosis and the
gastrointestinal manifestations of CVID. Apilimod mesylate selectively
inhibits this pathway, reduces over-production of IL-12 and IL-23, and
in pre-clinical and clinical studies has demonstrated the potential to
treat certain inflammatory diseases. Apilimod mesylate is also
currently in a large multinational Phase 2b trial for Crohn's disease.
<sniP>
-------------------------------------------------
God can cure your P! It's no role of the genetic dice after all?
http://www.alternet.org/blogs/themix/36636/
[...]
Sada's been pitching the book around; he recently spoke at McLean Bible
Church -- a mega-church at the center of the "exodus movement" that
holds that homosexuality is a cureable disease, like psoriasis or
athlete's foot. It's where South Dakota Senator John Thune worships.
<sniP>
randall note::: now the christians are saying it's saPachat? lol
--------------------------------------------------------------
Back to folk remedies again. Oregon Grape again,
http://www.newswise.com/articles/view/520769/
Newswise - Psoriasis is a difficult disorder to treat because the
severity and distribution of psoriatic plaques varies immensely, and
because current medications can have undesirable side effects. This
common skin disorder affects more than 4.5 million people in North
America.
But according to an article in the American Journal of Therapeutics
(March/April 2006, Volume 13, No. 2, p. 121-126), a natural preparation
from a plant holds promise for psoriasis sufferers.
Steve Bernstein and other researchers from the Dermatology and Cosmetic
Center in Rochester, New York conducted a randomized, double-blind,
placebo-controlled study using a proprietary topical cream prepared
with Mahonia aquifolium.
This plant, also known as the barberry, Oregon grape, or berberis,
grows wild in North and South American and Europe. It was initially
used in American folk medicine as an oral medication for inflammatory
skin diesases including psoriasis and syphilis.
Of the 200 psoriasis patients enrolled in the trial, 97 completed the
12-week course and 74 completed the same regimen using a placebo cream.
Bernstein and his colleagues traced a statistically significant
improvement of the signs and symptoms of moderate plaque psoriasis
compared with patients receiving placebo. The medication was well
tolerated when applied to the affected area twice a day for twelve
weeks. No significant side effects were reported by either the active
or control group.
The researchers concluded that the cream containing Mahonia aquifolium
extract is a safe and effective treatment for mild to moderate
psoriasis.
_______________________________________________
http://www.businessweek.com/ap/financialnews/D8HPMJ481.htm?campaign_id=apn_home_down&chan=db
MAY. 23 3:58 P.M. ET
Cambrex Corp. said Tuesday one of its subsidiaries will produce a serum
for a Merrimack Pharmaceuticals clinical study on autoimmune disease
treatments. The subsidiary, Cambrex Bio Science Hopkinton Inc., will
produce trial quantities of Merrimack's lead drug candidate, MM-093,
for the Phase II study. Privately held, Cambridge, Mass.-based
Merrimack is conducting the study to determine the serum's
effectiveness on a range of autoimmune diseases including rheumatoid
arthritis, multiple sclerosis and psoriasis
Their stock went up one cent.
They should have reported PSORIASIS not psoriasis.
Then they'd have doubled that increase!
----------------------------------------------------------------------------
Randall... I guess God only wants me to stay 98.6% clear
randall
P News alert from Wales.
http://www.prnewswire.co.uk/cgi/news/release?id=171787
New Patient Information Programme, Psoriassist Launched to Support
58,000 Psoriasis Sufferers in Wales
LONDON, May 25 /PRNewswire/ --
A new information programme Psoriassist has been launched today to
support the 58,000 people in Wales with psoriasis. Backed by leading
dermatology experts and patient groups, Psoriassist aims to raise
awareness of the condition as well as provide information and support
for people with psoriasis, to help them 'Get well informed, well
prepared' and to help them get their condition 'well controlled'.
The Psoriassist campaign is launched in conjunction with a Psoriasis
Conference 'Beyond Skin Deep' for healthcare professionals in Bristol
on 25th May, which will raise the profile of psoriasis and highlight
the unmet need for quality of information, research and education for
patients and healthcare professionals.
With research showing that psoriasis can impair quality of life to the
same degree as diabetes, heart disease and some cancers, healthcare
professionals have highlighted the need for quality information for
psoriasis sufferers.
Information will be available through the Psoriassist website
www.psoriassist.co.uk. Alternatively a Psoriassist booklet is available
by calling 0800-40-45-999.
Gladys Edwards, Chief Executive of The Psoriasis Association commented:
"The Psoriassist campaign will be of great benefit to people with
psoriasis. The more information people have about their psoriasis and
suitable treatment options the better able they are likely to be to
manage their condition."
This was reiterated by Dr Richard Goodwin, Consultant Dermatologist,
The Royal Gwent Hospital, who said that "Psoriassist will both empower
psoriasis patients and also help to raise awareness of the condition
amongst the general public as there is currently a great deal of
ignorance surrounding psoriasis."
The campaign is sponsored by LEO Pharma and was developed in
conjunction with The Psoriasis Association, Psoriasis Scotland
Arthritis Link Volunteers (PSALV), the British Association of
Dermatologists, the British Skin Foundation, the Skin Care Campaign,
dermatology experts and people affected by the condition
<sniP>
================================================
Breast cancer and markers of persistent fatique! Looks familiar doesn't
it?
http://today.reuters.com/news/newsArticle.aspx?type=healthNews&storyID=2006-05-20T004509Z_01_SIB002692_RTRUKOC_0_US-FATIGUE-BREAST-CANCER.xml&archived=False
NEW YORK (Reuters Health) - Breast cancer survivors often suffer from
persistent fatigue, and now researchers think they may have a handle on
what causes it.
Women with the problem appear to have significantly elevated levels of
a marker of inflammation called interleukin 6 or IL-6, and other
changes, according to a report in the journal Clinical Cancer Research.
"The study showed that there is an aberrant immune response in breast
cancer survivors with persistent fatigue," senior investigator Dr.
Michael R. Irwin told Reuters Health.
Irwin, at the David Geffen School of Medicine at the University of
California, Los Angeles, and colleagues note that the cause of
cancer-related fatigue remains poorly understood. They studied 32 women
who suffered from prolonged fatigue after battling breast cancer and 18
others who did not experience fatigue. The participants were recruited
at least 2 years after they had been successfully treated for cancer.
Several differences were seen between the groups. One was that cells
taken from the fatigued subjects produced more IL-6, as well as another
immune system compound called tumor necrosis factor alpha, in lab tests
than did cells from the non-fatigued group.
The team also found that other immune system measurements were "highly
diagnostic of fatigue."
"With this information," Irwin concluded, "we may now be able to
identify those patients at greatest risk for persistent fatigue and
develop targeted interventions early on that will lessen the severity
and duration of the fatigue."
(randall note:: To much extra TNF and IL-6 hanging around makes you
fatiqued? Sounds
familiar to me. I'm tired just reporting it. lol )
=============================================
Did you have a cute cat when you were a baby? Exposure to LPS
(endotoxins)
from your furry friend could have done you in eczema wise!
http://www.news-medical.net/?id=18086
According to new study in the U.S. children who are exposed to cats
soon after birth may have an increased risk of developing eczema, while
being exposed to two or more dogs at home may offer some slight
protection.
Lead researcher Esmeralda Morales, M.D., Pediatric Pulmonary Fellow at
the University of Arizona in Tucson, says other studies have found that
having cats or dogs at home appears to protect against allergic
diseases, so they expected to have similar findings.
Apparently pets are a source of a compound called endotoxin, and if a
child is exposed to endotoxin early in life, the immune system may be
skewed away from developing an allergic profile.
The study which tracked 486 children from birth, asked parents how many
cats and dogs they had in the house at the time the child was born, and
then followed up one year later to see which children had been
diagnosed with eczema.
It was found that of the 134 children with cats in the household, 27.6%
had eczema by one year of age, compared with 17.8% of 286 children
without cats.
That equates to more than a quarter of babies in cat households with
eczema by age 1, compared with one in six of children living without
cats.
While exposure to cats increased a child's risk of eczema whether or
not their mother had asthma, the effect was more pronounced in children
whose mothers did not have asthma.
Asthma could be a possible marker of mothers less likely to encourage
cat contact.
Previous studies have found that people with eczema have a higher
chance of also having allergic conditions including hay fever and
asthma.
Dr. Morales says that the children in the study who developed eczema at
age 1 might possibly end up having a reduced risk of asthma or other
allergic diseases later in life, but she believes the findings raise
more questions about pets and asthma and allergies.
Morales says much of the data already documented is contradictory and
there is clearly a need for further research.
Experts in the field say that while the study was interesting, it is
too early to draw firm conclusions as there are many questions about
the risk of exposure to pets and atopic diseases such as eczema, and
caution needs to be exercised before advising that pets should be
removed from the home environment.
Some scientists believe that unless the immune system is exposed to
adequate challenges in childhood it fails to develop properly.
Holy Cat crap batman! Does this mean my childhood skin problems
followed by early onset psoriasis was due to rusty the cat?
That's right Robbin, cat scratch fever got to you before Disco did!
--------------------------------------------------------------------------------------------
MINNEAPOLIS, MN, United States (UPI) -- University of Minnesota
scientists say they have found a group of cells in the intestinal
system of mice that turn on T-cells, which help fight infection.
'This connection between the group of cells and immune response will
help in studying and developing treatments for diseases that affect the
gastrointestinal system,' said Stephen McSorley, professor of medicine
and primary investigator on the project.
Researchers developed a tracking system that allowed them to identify
when T-cells are activated in response to a salmonella infection.
T-cells are one type of white blood cell involved in the body`s immune
system that helps fight infection.
The researchers discovered a tiny population of cells in the intestine
signal the T- cells to fight infections. 'Without these cells, the
T-cells are blind and the body`s immune response in the intestinal
system would not engage to fight the infection,' McSorley said.
While a mouse model was used in the research, McSorley says researcher
now will examine human tissue samples to possibly identify similar
process.
He added this population of cells may be important in many responses in
the gastrointestinal system, which may be helpful in studying diseases
and conditions such as ulcerative colitis and Crohn's disease.
The research, conducted in collaboration with scientists at Harvard
University, appears in the current issue of the journal Immunity.
_______
This is a good one. The one above this!
Lets see what we can find on similar posts regarding the same topic,
http://www.medicalnewstoday.com/medicalnews.php?newsid=43931
This guy could be on the front lines of the P war,
http://www.med.umn.edu/gi/faculty/mcsorley.html
Shouldn't be hard to find his pubmed abstract. How many Mcsorley's are
there?
Here it is,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16713979
CCR6-Mediated Dendritic Cell Activation of Pathogen-Specific T Cells in
Peyer's Patches.
Salazar-Gonzalez RM, Niess JH, Zammit DJ, Ravindran R, Srinivasan A,
Maxwell JR, Stoklasek T, Yadav R, Williams IR, Gu X, McCormick BA,
Pazos MA, Vella AT, Lefrancois L, Reinecker HC, McSorley SJ.
Department of Medicine, GI Division and Center for Infectious Diseases
and Microbiology Translational Research, University of Minnesota
Medical School, McGuire Translational Research Facility, TRF DC 2873,
2001 6th Street S.E., Minneapolis, Minnesota 55455.
T cell activation by dendritic cells (DCs) is critical to the
initiation of adaptive immune responses and protection against
pathogens. Here, we demonstrate that a specialized DC subset in Peyer's
patches (PPs) mediates the rapid activation of pathogen specific T
cells. This DC subset is characterized by the expression of the
chemokine receptor CCR6 and is found only in PPs. CCR6(+) DCs were
recruited into the dome regions of PPs upon invasion of the follicle
associated epithelium (FAE) by an enteric pathogen and were responsible
for the rapid local activation of pathogen-specific T cells.
CCR6-deficient DCs were unable to respond to bacterial invasion of PPs
and failed to initiate T cell activation, resulting in reduced defense
against oral infection. Thus, CCR6-dependent regulation of DCs is
responsible for localized T cell dependent defense against
entero-invasive pathogens.
PMID: 16713979
May as well see all of his for a clue or two,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22McSorley+SJ%22%5BAuthor%5D
We've gone over the peyer's patches more then a few times,
http://groups.google.com/groups/search?q=peyer%27s+patches+psoriasis+randall&qt_s=Search
And look at that issue of immunity. (Volume 24 Issue 5: May 2006)
http://www.immunity.com/
And found this,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16713965
And we've had the LAT protein as a suspect here,
http://groups.google.com/groups?hl=en&q=lat%20linker%20activation%20randall%20psoriasis&btnG=Google+Search&sa=N&tab=wg
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20lat+linker
This one is suspect,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16403671
PMID: 16403671
So many of these have a term i'm not familiar with.
Google is moving to slow.
http://www.ask.com/web?q=what+is+Palmitoylation&qsrc=0&o=312
Oh boy! Easier to stay with pufa's and enhanced LAT activations. lol
All brings us back to a vegetarian diet, NO milk or wheat and drink
peanut milk. lol
So lets ask some more questions,
http://www.ask.com/web?q=+Palmitoylation+pufa&qsrc=1&o=312
&
http://www.ask.com/web?q=+Palmitoylation+pufa+n-6&qsrc=1&o=312
&
Backing pufa out and adding LPS in,
http://www.ask.com/web?q=+Palmitoylation+n-6+lps&qsrc=1&o=312
And moving backwards to another abstract,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16102570
Role of the LAT adaptor in T-cell development and Th2 differentiation.
Malissen B, Aguado E, Malissen M.
Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Universite de la
Mediterranee, Parc Scientifique de Luminy, Case 906, 13288 Marseille
Cedex 9, France.
LAT (linker for activation of T cells) is an integral membrane adaptor
protein that constitutes in T cells a major substrate of the ZAP-70
protein tyrosine kinase. LAT coordinates the assembly of a multiprotein
signaling complex through phosphotyrosine-based motifs present within
its intracytoplasmic segment. The resulting "LAT signalosome" links the
TCR to the main intracellular signalling pathways that regulate T-cell
development and T-cell function. Early studies using transformed T-cell
lines suggested that LAT acts primarily as a positive regulator of
T-cell receptor (TCR) signalling. The partial or complete inhibition of
T-cell development observed in several mouse lines harboring mutant
forms of LAT was congruent with that view. More recently, LAT
"knock-ins" harboring point mutations in the four COOH-terminal
tyrosine residues, were found to develop lymphoproliferative disorders
involving polyclonal T cells that produced high amounts of T
helper-type 2 (Th2) cytokines. This unexpected finding revealed that
LAT also constitutes a negative regulator of TCR signalling and T-cell
homeostasis. Although LAT is also expressed in mast cells, natural
killer cells, megakaryocytes, platelets, and early B cells, the present
review specifically illustrates the role LAT plays in the development
and function of mouse T cells. As discussed, the available data
underscore that a novel immunopathology proper to defective LAT
signalosome is taking shape.
PMID: 16102570
Lets zap the zap,
http://groups.google.com/groups/search?q=zap-70+psoriasis&qt_s=Search
&
http://groups.google.com/groups/search?q=zap-70+&qt_s=Search
&
http://images.google.com/images?q=zap-70&qt_s=Search&sa=N&tab=gi
And burning out!
randall... P news gets confusing fast if you let it!
randall
It's been five days since a P news. Are you ready?
Don't get to excited, this isn't the Indy 500 with a record book
ending.
Doing inflammation for the 500th time.
http://news.biocompare.com/newsstory.asp?id=136394
U Of M Researchers Find Immune-Activating Cells In Intestines
5/23/2006
Source: University of Minnesota
Discovery may suggest future treatments for intestinal disorders
University of Minnesota researchers have found a group of cells in the
intestinal system of mice that are proven to turn on T-cells, cells
that help fight infection.
The research will be published in the May 2006 issue of the journal
Immunity, released today.
"This connection between the group of cells and immune response will
help in studying and developing treatments for diseases that affect the
gastrointestinal system," said Stephen McSorley, Ph.D., professor of
medicine and primary investigator on the project.
Researchers at the University developed a tracking system that allowed
them to identify when T-cells are activated in response to a salmonella
infection. T-cells are one type of white blood cell involved in the
body's immune system that helps fight infection.
The researchers found a tiny population of cells in the intestine that
signal the T- cells to fight infections. "Without these cells, the
T-cells are blind, and the body's immune response in the intestinal
system would not engage to fight the infection," McSorley said.
While the researchers used a mouse model to find this cell group,
McSorley said in the future they will examine human tissue samples to
try to identify a similar group in people.
He added this population of cells may be important in many responses in
the gastrointestinal system, which may be helpful in studying diseases
and conditions such as ulcerative colitis, and Crohn's disease.
The research was done in collaboration with scientists at Harvard
University.
================================================
http://news.biocompare.com/newsstory.asp?id=136407
Research Reveals Control Of Potent Immune Regulator
5/24/2006
Source: Ohio State University
A new study reveals how the production of a potent immune regulator
called interferon gamma (IFNg) is controlled in natural killer (NK)
cells, immune cells that typically defend the body against cancer and
infections.
IFNg, produced by NK cells and other cell types, plays a critical role
in killing pathogen-infected cells and in defending against tumor
cells. However, overproduction of IFNg is also dangerous to the body
and can cause autoimmune diseases. But exactly how the body tightly
controls IFNg production - and, therefore, NK-cell activity - is
not known.
The study, published in the May issue of the journal Immunity, looked
at substances called pro-inflammatory cytokines, which cause NK cells
to make IFNg and stimulate their activity. It also looked at
transforming growth factor beta (TGFb), a substance also made by NK
cells that lowers IFNg production.
The research, by investigators with the Ohio State University
Comprehensive Cancer Center - Arthur G. James Cancer Hospital and
Richard J. Solove Research Institute, found that the pro-inflammatory
cytokines not only cause NK cells to make IFNg, but they also shut down
TGFb signaling, which inhibits production of IFNg.
That is, the cytokines not only increase some positive regulators of
IFNg production, but they also shut down the TGFb signals that inhibit
IFNg production.
In addition, the scientists found that TGFb turns down IFNg production
- and, therefore, NK cell activity - both directly and indirectly.
The direct mechanism turns off the IFNg gene itself. The indirectly
mechanism blocks a protein that normally turns up IFNg production.
"Our findings provide important details about the fine balance
between positive and negative regulators of IFNg production in NK
cells," says principal investigator Michael A. Caligiuri, director of
the OSU Comprehensive Cancer Center. "Mother Nature uses a symphony
of cytokines that result in exquisitely tight control of its production
in the healthy state.
"This might help us harness the cancer-killing ability of NK cells to
control tumor growth and lead to new treatments that complement current
cancer therapy," he says.
The body carefully regulates IFNg levels. If there is too little of the
substance, the risk of infection and cancer rises. If there is too much
IFNg, NK cells become too plentiful and autoimmune diseases such as
inflammatory bowel disease can occur.
"Our findings explain the yin and yang of the system that controls NK
cells," says first author Jianhua Yu, a post-doctoral student in
Caligiuri's laboratory. "When NK cells are called into action, the
body not only turns up the activation pathway, it also shuts down the
anti-activation pathway."
Likewise, when TGFb turns down NK cell activity, it not only turns off
the IFNg gene, it also shuts down the pathway that activates the gene.
"In each instance, these regulatory cytokines deliver a double
whammy," Caligiuri says. "They turn on what is needed and turn off
anything that interferes with it."
Funding from the National Cancer Institute supported this research.
==============================================
http://news.biocompare.com/newsstory.asp?id=136968
New Pathways For Autoimmune Treatment Identified
5/28/2006
Source: Medical College of Georgia
A rare genetic defect that can trigger a host of diseases from type 1
diabetes to alopecia has helped explain the imbalance of immune
regulator and killer cells in autoimmune disease.
Mutation in the Aire gene causes APS1, a disease causing two out of
three problems - an underactive parathyroid, yeast infection of the
skin and/or mucous membrane and adrenal gland insufficiency - by age
5 and up to 16 autoimmune diseases over a lifetime.
The same mutation causes a defect in iNKT cells, a type of regulatory
cell that helps the immune system fight infections while suppressing
errant T cells bent on attacking the body, Medical College of Georgia
researchers say.
This finding opens new pathways for treating or preventing APS1, or
autoimmune polyglandular syndrome type 1, and potentially other
autoimmune diseases as well, researchers report in the June issue of
Nature Medicine.
"The body should maintain a balance between killing and
suppression," says Dr. Qing-Sheng Mi, immunologist and lead and
co-senior author. "If you are killing too hard, it can induce
autoimmune disease. If you regulate suppression too hard, you can get
cancer. iNKT cells help maintain a healthy balance. But patients with
autoimmune disease may not have enough functional iNKT cells."
"Aire controls the development and function of iNKT cells," says
Drs. Jin-Xiong She, director of the MCG Center for Biotechnology and
Genomic Medicine and co-senior author. "This relationship means that
iNKT cells are critical to most autoimmune diseases and manipulating
the iNKT cell population is one possible way to cure autoimmune
disease."
A lipid purified from sea plants, called alpha-GalCer, is already under
study as a way to boost iNKT cell numbers and fight autoimmune disease
as well as cancer. iNKT cells' reactivity to alpha-GalCer, prompted
the scientists to use it as a marker to examine the status of these
cells in a mouse missing the Aire gene. That Aire knockout is a good
model for humans with APS1.
They found significantly fewer iNKT cells in the thymus, spleen, liver
and bone marrow and severely impaired maturation of those cells in mice
missing the Aire gene. And the mice given alpha-GalCer had
significantly reduced autoantibody production.
In 2001, Dr. Terry L. Delovitch and his colleagues at Canada's
Robarts Research Institute, including Dr. Mi, reported in Nature
Medicine that using alpha-GalCer to boost iNKT cells and re-establish a
healthy balance of good and bad immune cells prevented development of
type 1 diabetes in an animal model for the disease.
But Drs. Mi and She say new iNKT boosters likely are needed because the
action of alpha-GalCer somehow depends on individual genetic
architecture as well as other factors. Under certain conditions, the
drug can help or worsen an autoimmune disease by producing good or bad
cytokines. That's why it also has worked for some cancers and why a
modified version of the glycolipid or totally different drugs may work
better, Dr. She says. "By understanding more, we are better able to
come up with better targets," he says.
"iNKT development is still the big question," says Dr. Mi. "Not
only how they develop, but how they develop properly."
The researchers watched the key regulatory cells come out of the bone
marrow and go to the thymus where all T cells go for a process of
positive and negative selection and maturation. Positive selection
eliminates cells that are dysfunctional. Negative selection is
eliminating T-cells that recognize the body's own proteins, Dr. She
says.
Other researchers recently confirmed that the Aire gene is involved in
negative selection by controlling some protein expression in the
thymus, Dr. Mi says. The thymus is supposed to express most body
proteins so any T cells that would react to them can be eliminated
through negative selection, he says. "But Aire's role in protein
expression is not sufficient to explain all the clinical symptoms of
patients with APS1," Dr. Mi says. "The Aire gene must have other
immune functions."
iNKT cells also go through a development process but via a somewhat
different path than that of other T cells. MCG researchers have learned
medullary epithelial cells in the thymus are critical to proper iNKT
cell development. A defective Aire gene disrupts this natural nurturing
relationship by disrupting medullary epithelial cell function, leading
to insufficient numbers of iNKT cells.
"Whether or not you develop autoimmune disease to a large degree
depends on the balance of these bad T cells that recognize the body's
own protein and regulatory T cells," Dr. She says. "It's all
about balance."
Dr. Mi received a Junior Faculty Travel Award from the American
Association of Immunologists for the iNKT research during the
association's annual meeting in May.
The research was supported by the American Diabetes Association, the
Juvenile Diabetes Research Foundation, the National Institutes of
Health and the Canadian Institutes of Health Research.
Co-authors include Drs. Zhong-Bin Deng, Sunil K. Jushi, Zai-Zhai Wang,
Li Zhou, Sarah Eckenrode, Ratnmani Joshi as well as Bing Yi from MCG
and Dr. Delovitch and Ph.D candidate Dalam Ly from the Robarts Research
Institute and the University of Western Ontario
---------------------------------------------------------------------
http://news.biocompare.com/newsstory.asp?id=136415
New Approach To Vaccine Development Provides Potent, Long-Lasting
Immunity
5/24/2006
Source: University of Pittsburgh Medical Center
The field of vaccine development is getting a boost from new research
that has identified a promising vaccine delivery approach, which in
animal studies produced long-term immune protection after just one
immunization. University of Pittsburgh researchers, who report their
findings in the journal Immunity, say the method has particular
relevance for efforts aimed at preventing or controlling infectious
diseases, such as HIV or influenza, or stopping the growth of cancer.
In one set of studies using this delivery approach, a single
immunization halted the progression of melanoma and significantly
extended survival in a mouse model.
The approach makes use of an inactivated retrovirus, in this case, a
modified lentiviral vector more commonly known for its ability to carry
functional genes in certain types of gene therapy. Viral vectors in
general have been of practical interest to vaccine researchers for
their potential to deliver antigens from disease-causing microbes, or
even cancer, in order to efficiently build immune defenses against such
intruders. To date, the lentivirus has been overlooked in vaccine
research. But, according to Pitt investigators, it has distinct
advantages that make it a more promising approach for vaccine
development than other viral vector or DNA-based vaccine approaches
previously studied.
According to results of their studies, a single injection of the
lentivector containing either a hepatitis B virus antigen, a melanoma
tumor antigen, or a commonly studied model antigen induced a more
potent and notably, long-lasting immune response compared to other
immunization approaches. A population of specialized immune cells that
reside within the top layers of the skin is due much of the credit, say
the authors.
"Skin dendritic cells have long been considered the immune system's
first line of defense," explains Louis D. Falo, Jr., M.D., Ph.D.,
professor and chairman of the department of dermatology, University of
Pittsburgh School of Medicine, and the study's senior author. "But
recent studies that looked at different viral vectors, including the
most commonly studied vaccinia vector, have challenged this notion,
suggesting that skin dendritic cells are not as important as the
classical paradigm maintained. We find that with the lentivirus, it's
precisely these skin dendritic cells that are responsible for the
vector's more potent immune induction and sustained protection."
Because they exist on the surface of the skin, these cells are the
first to recognize the presence of a foreign body, or antigen. Although
no longer an active virus, the lentivector is cause enough for alarm,
so the dendritic cells capture their prey and then journey to the lymph
nodes with their captured invaders - the vector, and the antigens in
the vector as stowaway passengers. In the lymph nodes, the dendritic
cells present their bounty to the waiting T cells and program them to
attack the foreign invader, subsequently generating the appropriate
immune response.
As the other studies have found, and the Pitt team confirms,
skin-derived dendritic cells play a lesser role when other vectors are
used, merely serving as the transport system to the lymph nodes, where
another population of dendritic cells takes over and presents the
antigen to the T cells.
Importantly, the investigators found that despite being a foreign
intruder itself, the lentivirus seemed to escape the notice of the
immune system, even when introduced a second time, suggesting that it
could be used repeatedly in the same patients.
"You might say the other viral vectors are a one-shot deal because the
immune system recognizes the virus and responds against it the second
time around," suggests Dr. Falo. "With lentivirus, it seems feasible to
use the immunization approach multiple times in the same patient, such
as for annual flu vaccination, or in preventing multiple different
infections or cancers in the same patient or in the general
population."
Taken together, the investigators say their findings have implications
for the development of vaccines that involve cell-mediated immunity,
including viral and bacterial infections, and cancer. In the next
three-to-five years, they expect to initiate a clinical trial of the
approach, most likely for patients with melanoma.
===================================================
http://news.biocompaer.com/newsstory.asp?id=136403
Immune Signals Of Variations Of A Single Gene Linked To More Severe
Crohn's Disease
5/24/2006
Source: Cedars-Sinai Medical Center
Building on previous evidence supporting the theory that the
pathophysiology of Crohn's Disease is altered by genetic variation,
recent studies have found that the combination of immune signals given
by three variants of a single candidate gene affects the severity of
the disease, particularly among Ashkenazi Jews. The findings, presented
at the annual meeting of the American Gastroenterological Association,
were reported by researchers from Cedars-Sinai Medical Center, the
University of Washington and Mount Sinai School of Medicine.
Crohn's Disease is an inflammatory bowel disease that causes
inflammation or ulceration of the gastrointestinal tract and can
sometimes run in families. While the cause is unknown, many
professionals believe that the body's immune system may overreact to
normal intestinal bacteria or that disease-causing bacteria and viruses
may play a role in triggering the condition.
The recent study, funded by the National Institutes of Health, shows
the effect of one particular gene - a Crohn's Disease candidate gene
named TLR 5 - on both Jews and non-Jews with the disease.
It is estimated that American Jews are three times more likely to
develop Crohn's Disease than the population as a whole. Approximately
80 percent of the six million Jews in the United States are Ashkenazi
Jews, an ethnic group whose ancestors are from eastern and central
Europe,
As Jerome I. Rotter, M.D., first author of the study, director of
research and co-director of the Medical Genetics Institute at
Cedars-Sinai Medical Center explained, the innate immune system senses
micro-organisms and pathogens using a family of proteins known as the
Toll-Like Receptors (TLRs). This recognition activates both the innate
and adaptive immune system, with each TLR recognizing a specific
pattern of microbial components.
The aim of the study was to investigate three TLR5 gene variants and
their relationship to Crohn's Disease, the response to two types of
bacterial antigens (OmpC porin and CBir1 flagellin) and their
relationship to ethnicity. There were 889 Crohn's Disease patients in
the study and 236 controls (persons without Crohn's Disease).
"An important part of the study was its approach. By subdividing the
subjects by ethnicity and antibody response we were able to show that
the candidate gene TLR5 has an effect in both Jews and non-Jews, but
its effects are particularly noteworthy in the Jewish population,"
Rotter said.
While the treatment of Crohn's Disease is improving, it is still
associated with a high morbidity and a large number of hospitalizations
and surgeries, Rotter said. "This study demonstrates that it will be
important to include ethnicity, clinical phenotypes and quantitative
physiologic traits in future investigations that may eventually lead to
new and better therapies for Crohn's Disease's different sub-forms."
====================================================
http://news.biocompare.com/newsstory.asp?id=136855
Plague Agent Helps UT Southwestern Researchers Find Novel Signaling
System In Cells
5/25/2006
Source: UT Southwestern Medical Center
The bacterium that causes bubonic plague would seem unlikely to help
medical scientists, but researchers at UT Southwestern Medical Center
have harnessed it to uncover a new regulatory mechanism that inhibits
the immune system.
Three species of the Yersinia bacteria, known to cause plague and
gastroenteritis, contain a small molecule, called a virulence factor,
that the researchers have found modifies host enzymes critical to
normal functioning.
"This type of modification has never been seen in cells and presents a
new paradigm for how cells may regulate signaling," said Dr. Kim Orth,
assistant professor of molecular biology and senior author of the study
appearing in the May 26 edition of Science.
"Yersinia is a nasty pathogen that uses an arsenal of virulence factors
to cause disease," she said.
When a cell is infected with a bacterial pathogen, it activates a chain
of reactions involving enzymes. One enzyme adds a group of atoms
containing phosphorus - called a phosphate group - to another
enzyme, a process called phosphorylation, which spurs that enzyme to
add a phosphate group to yet another enzyme, and so on. These
"cascading" events trigger an appropriate immune response.
Yersinia, however, has the ability to prevent its host from mounting
the response, enabling the bacteria to survive and multiply.
The researchers found that one of the Yersinia outer proteins, called
YopJ, cripples these cascades by adding a small molecule called an
acetyl group to two key sites on a host enzyme where the phosphate
groups are usually added.
Because the host's enzymes are modified by acetyl groups, they can no
longer be activated by phosphate groups, and the enzymatic cascade
critical for triggering an innate immune response is not activated.
The internal signaling that YopJ affects is common to many species,
from yeast to mammals. In addition, other pathogens that attack animals
and plants use proteins that are similar to YopJ.
The research is not geared toward finding a cure for plague, which
affects about a dozen people in the United States a year and is
treatable with antibiotics. Instead, the scientists are working to find
out how the pathogen disrupts the immune system and to understand the
machinery critical for stimulating an immune response.
"There are many virulence factors used by bacterial pathogens to co-opt
the host signaling molecules," Dr. Orth said. "These virulence factors
affect central signaling machinery, and we want to understand how they
are doing it."
Understanding the relationship between the pathogens and the hosts will
help researchers uncover critical steps in how host cells normally
operate, Dr. Orth said.
"The next step is to see whether the addition of acetyl groups to key
sites on enzymes during cellular signaling is normal for animal and
plant cells, and if so, under what circumstances," said Dr. Orth.
Other UT Southwestern researchers involved in the study were first
author Sohini Mukherjee, student research assistant in molecular
biology; Gladys Keitany, research assistant in molecular biology; Dr.
Yan Li, instructor of biochemistry; Yong Wang, research assistant in
molecular biology; Dr. Haydn Ball, assistant professor of biochemistry;
and Dr. Elizabeth Goldsmith, professor of biochemistry.
The work was supported by the National Institute of Allergy and
Infectious Diseases, the Beckman Foundation and the Welch Foundation.
=============================================
http://www.merckmedicus.com/pp/us/hcp/hcp_newsarticle.jsp?newsid=651908&newsgroup=2
TLR8 agonists stimulate Th1 immune responses in newborns
The inability of neonates to mount a T helper cell type 1 (Th1)-type
immune response, which makes them susceptible to infections and
prevents them from responding to vaccines, may be overcome by drugs
that activate Toll-like receptors.
Specifically, the results of a new study suggest that an agonist of one
type of Toll-like receptor, TLR8, activates neonatal antigen-presenting
cells and production of a Th1 response. "These properties suggest that
TLR8 agonists may fulfill a unique role as potential adjuvants for
neonatal vaccines," Dr. Ofer Levy and colleagues suggest in their
report, published in the online edition of the journal Blood.
Dr. Levy, from Harvard Medical School, and his group explain that
newborn cord blood monocytes do not respond to most TLR agonists.
However, the researchers previously reported that the TLR 7/8 agonist
R-848, but not a pure TLR7 agonist, activates neonatal monocytes to
produce the Th1-polarizing cytokine tumor necrosis factor (TNF)-alpha.
To test their theory that TLR8 is the component that activates
newborns' immune system, the investigators isolated monocytes from
blood of 33 healthy adult volunteers, and from cord blood of 33
newborns. They tested a panel of TLR agonists, and found that only
those that signal via TLR8 induced TNF-alpha production in the
newborns' cells at levels equivalent to that in adult blood.
In both newborn and adult monocytes, TLR8 agonist caused
phosphorylation of p38 MAP kinase and induced disappearance of
I-kappa-B-alpha, an inhibitor of the transcription of certain genes
associated with inflammation. These factors "may contribute to the
efficacy of TLR8 agonists in activating neonatal and adult
antigen-presenting cells," the authors surmise.
Further study revealed that TLR8 expression by monocytes and myeloid
dendritic cells was similar in newborns and adults.
"We have discovered that agents that activate cells via TLR8 have a
unique ability to induce production of Th1-responses in neonatal
antigen-presenting cells, revealing a unique preservation of the
TLR8-mediated activation pathway in human newborns," Dr. Levy's team
conclude, saying the findings represent "a significant advance in
neonatal immunology."
They say that TLR7/8 or TLR8 agonists "may play important roles in
treating and/or preventing diseases by enhancing innate and acquired
responses in human newborns."
-------------------------------------------------------------------------------------
randall... hey---science is fun!
randall
P news from around the world.
http://www.medadnews.com/News/index.cfm?articleid=345339
Biogen Idec to Acquire Fumapharm AG
CAMBRIDGE, Mass. and LUCERNE, Switzerland (May 31, 2006) - Biogen Idec
(NASDAQ: BIIB) and Fumapharm AG, a privately held pharmaceutical
company, today announced that they have signed a definitive agreement
for the acquisition of Fumapharm by Biogen Idec.
Fumapharm AG, founded in Switzerland in 1983, develops therapeutics
derived from fumaric acid esters for patients with high unmet medical
need. The company has two products: FUMADERM®, a commercial product
available in Germany for the treatment of psoriasis, and BG-12, a
clinical-stage product that has been jointly developed with Biogen
Idec. BG-12, an oral fumarate, is being studied for the treatment of
multiple sclerosis (MS) and psoriasis. <sniP>
Ok, what do you think?
Will we get fumaderm sooner or later due to this?
=========================================
This page was sent to me for the P and Morgellons.
http://www.med-owl.com/psoriasis/tiki-index.php
Check out the photocoPier page. Goes along with smoking!
Could it be a reason for wintertime P blues?
Take more NAC during the winter time seemed smart to
me!
---------------------------------------------------------------
Abstracts::
Evaluation of the anti-proliferative properties of selected
psoriasis-treating Chinese medicines on cultured HaCaT cells.
Tse WP, Che CT, Liu K, Lin ZX.
School of Chinese Medicine, Faculty of Science, The Chinese University
of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Psoriasis is a chronic inflammatory skin disorder, which affects
approximately 2-3% of the population worldwide. The current
conventional therapy cannot offer satisfactory clinical results for
most of the patients, largely due to the fact that many anti-psoriatic
drugs have serious side effects and psoriasis is prone to developing
drug resistance after long term exposure. Traditionally, Chinese herbal
medicine has been extensively used to treat psoriasis and produced
promising clinical results; however, its underlying mechanisms of
action have not been systematically investigated. The aim of this study
was to investigate those Chinese medicinal materials, which are
commonly prescribed in Chinese medicine practice for psoriasis, for
their anti-proliferative effects on HaCaT cells in vitro. Sixty Chinese
medicinal materials were selected and extracted with 80% aqueous
ethanol. The dry extracts were evaluated for their anti-proliferative
activities by microplate SRB and MTT assays. Three Chinese medicinal
materials i.e. the root of Rubia cordifolia L. (Rubiaceae), Realgar and
the rhizome of Coptis chinensis Franch. (Ranunculaceae) were found to
have significant anti-proliferative effects, with IC(50) being 1.4, 6.6
and 23.4mug/ml, respectively as measured by MTT assay. While Realgar
was also able to modestly inhibit the growth of Hs-68 cells in vitro,
Rubia cordifolia and Coptis chinensis did not exert cytotoxicity to
this human fibroblast cell line.
PMID: 16730935
Robo-poster was right!
Immunomodulation in dermatology: lessons learned in the treatment of
psoriasis.
Charlesworth EN.
Department of Allergy and Dermatology, Shannon Clinic, San Angelo,
Texas, USA. echarl...@shannonhealth.org
With the widespread recognition that T-cells are the key mediators of
psoriasis, current treatment strategies have focused on reducing the
population of these cells or modulating their activity through the use
of immunosuppressive treatments such as methotrexate, cyclosporine, and
psoralens plus ultraviolet A radiation. Now, a greater understanding of
the immunologic basis of psoriasis based on scientific advances are
enabling the development of rationally designed, biologic agents that
selectively target specific elements in the immune system that are
directly involved in the pathophysiology of psoriasis. This review
discusses several basic strategies for biologic therapies for psoriasis
and concludes that the ___allergist/immunologist___ is eminently
qualified to treat this immune skin disorder.
PMID: 16724630
This sounds really bad!
A case of severe eczema following use of imiquimod 5% cream.
Taylor CL, Maslen M, Kapembwa M.
Department of Genitourinary Medicine, Northwick Park Hospital, Watford
Road, Harrow, Middlesex HA1 3UJ, UK. clare...@doctors.net.uk.
Imiquimod 5% cream, an immune response modifier licensed for treatment
of external ano-genital warts and superficial basal cell carcinomata,
is known to cause local erythema, oedema and, rarely, exacerbation of
psoriasis. We describe a case of exacerbation of eczema following
application of this cream in a man with penile warts.
PMID: 16731674
Out of the one million plus folks in the UK that get P, this guy had
the unfortunate luck
to make the case.
--------------------------------------------
randall....
randall
P News from around the world.
>From the Middle East,
http://www.ameinfo.com/87704.html
Region's first psoriasis patient support group introduced in Bahrain
The first patient support group for psoriasis sufferers concluded its
inaugural meeting today in Bahrain.
[...]
The meeting included a presentation by Dr. Nidhal Khalifa, Consultant
Dermatologist and Head of Dermatology Department, Salmaniya Medical
Complex, Bahrain, on improving the quality of life for those living
with psoriasis. <sniP>
==============================================
Ireland today,
http://www.vhi.ie/news/n010606b.jsp
Psoriasis Information Online
A new psoriasis information website was launched recently by Tanaiste
and Minister for Health & Children, Mary Harney.
www.psoriasisireland.ie, run by the Psoriasis Association of Ireland,
has information on causes, treatments and management. Users can also
communicate with other psoriasis sufferers through online discussion
boards.
"Psoriasis is a chronic, disfiguring, inflammatory and non-contagious
disease of the skin," said Dr Colin Bradley, consultant dermatologist
in Waterford regional hospital and president of the Association. "It
is known that trauma, infection, stress and certain medications can
precipitate the first appearance of psoriasis or an exacerbation of
existing disease."
Caroline Irwin, founder and chairperson of the Association said until
now, many people with psoriasis suffered in silence and isolation.
"One of the biggest problems for people has been the lack of
information about the condition, new treatments and the correct
application of medications. Our website will provide a major
communication tool for the thousands of sufferers and their families
throughout the country."
==============================
If you want to be the queen bee at the sPelling bee's currently
taking place, you best know how to spell P and exzema, <w>
http://www.fortwayne.com/mld/newssentinel/news/editorial/14715069.htm
&
http://www.spellingbee.com/
===================================
Abstracts:
Is your P only an allergy?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16734502
Prospects for vaccines for allergic and other immunologic skin
disorders.
Medi BM, Singh J.
Department of Pharmaceutical Sciences, College of Pharmacy, North
Dakota State University, Fargo, North Dakota, USA.
The human skin hosts a variety of immune response-associated components
that together form the skin immune system. Any abnormality in the
functioning of the skin immune system leads to a variety of
dermatologic complications, including dermatitis, psoriasis, and
eczema. Exposure to antigens/allergens can lead to allergic skin
disorders such as atopic dermatitis, urticaria, and allergic contact
dermatitis. Recent investigations have provided new insights into the
immunologic processes leading to the development of skin diseases. T
cells play a central role in the activation and regulation of immune
responses by recognizing antigen and inducing cytokine production.
Despite advances in the understanding of the immunologic events leading
to the development of skin diseases, no effective prevention measure
exists. Current therapeutic treatments are based on either alleviating
the symptoms or suppressing the immune system with immunosuppressive
drugs. Allergen-specific immunotherapy is expected to induce specific T
cells that abolish allergen-induced proliferation of T helper cells, as
well as their cytokine production. Recent approaches using recombinant
protein, polycytosine guanine oligonucleotides, and plasmid DNA for
vaccination suggest the possibility of protection against these skin
disorders. The involvement of T cells in psoriasis indicates that the
development of a T-cell receptor peptide vaccine may be beneficial.
Dendritic cell-based vaccines using tolerogenic dendritic cells that
can induce T-cell tolerance have been shown to be useful in dealing
with autoimmune disorders and allergic conditions. In the light of
these developments, this article presents the current status and
prospects of developing vaccines for allergic and other immunologic
skin disorders.
PMID: 16734502
The Russians are on the P genes today,
[The molecular genetics of psoriasis]
[Article in Russian]
[No authors listed]
The review is dedicated to molecular-and-genetic aspects of psoriasis.
The paper contains a general characterization of this skin disease and
a range of hypotheses concerning its appearance, clinical
manifestations, and maintenance. Its autoimmune nature with the central
role played by T-cells is considered to be the basic theory of the
appearance of psoriasis. According to the results of analysis of
experimental data on psoriasis genetics, including family background,
psoriasis is defined as a complex multigene multifactor disease, whose
manifestations are determined by a combination of certain genes as well
as by various environmental trigger factors. The authors consider
ethnic features of psoriasis, and genes that determine predisposition
to the disease. Prospects of the search of predisposition genes,
including analysis of the polymorphism of unit nucleotides, are
outlined in the article.
PMID: 16734342
Whatever turns you on P wise, we know the biologicals are all the rage.
[New systemic treatments for psoriasis: etanercept, infliximab,
adalimumab, efalizumab and alefacept]
[Article in Dutch]
Bos WE, Thio HB, Neumann HA, van der Fits L, Prens EP.
Erasmus MC, afd. Dermatologie & Venereologie, Postbus 2040, 3000 CA
Rotterdam.
The chronic skin disease psoriasis frequently requires long-term
systemic treatment with agents that suppresses the immune system with
little specificity, which can lead to systemic side effects. Today,
using recombinant techniques, it is possible to produce modified
proteins, the so-called biologicals, that target specific molecules in
the inflammatory process. For the biologicals etanercept, infliximab,
adalimumab, efalizumab and alefacept, the clinical efficacy expressed
in the rates of partial remission (75% reduction in skin lesions) in
patients with plaque psoriasis range from 12 to 88%, compared with 22
to 87% for existing systemic therapies for psoriasis. The side effects
of biologicals are usually mild to moderate, but can sometimes be
severe. The biologicals should be prescribed with caution, given that
they have been on the market for a relatively short period, and because
all forms of immune suppression carry an increased risk of oncologic
degeneration. The guideline of the Dutch Society of Dermatology and
Venereology states that the use of a biological may be considered when
a patient cannot tolerate or is unresponsive to conventional systemic
therapy, or has an increased risk of adverse events. Biologicals
increase the number of options for treatment-resistant plaque
psoriasis, which allows therapy to be tailored to the individual
patient.
PMID: 16733982
++++++++++++++++++++++++++++++++++++++++++++++
Hey! Where's robo poster? I'm expecting to eat crow for suPPer?
randall... maybe he's allergic to my posts?
randall
P News from around the world.
Hey! How'd that get in here?
Back to P. The man eating P fish of Kangal, Turkey...
http://www.timesonline.co.uk/article/0,,8123-2207066,00.html
The Times June 03, 2006
Body&Soul
Spas: A swim with man-eating fish
Louise Murray visits the "doctor fish" at a Turkish spa, which, it
is claimed, can relieve psoriasis
There are easier ways to exfoliate than immersing oneself in a hot spa
pool with hundreds of voracious fish. But that is what I am doing in
Kangal, in Central Anatolia, Turkey.
The spa sits beside a snow-melt swollen river, in a valley 1,600m
(5,250ft) up in the mountains of this remote agricultural region. It
has made a name for itself, and its resident "doctor fish" (Garra
rufa obtusa), as a treatment for psoriasis, a painful skin complaint
that afflicts about 2 per cent of the UK population.
The healing powers of the fish were discovered by a shepherd and his
flock in 1917. He stumbled into marshy ground with an injured foot and
found the open wound besieged by fish. The wound healed and eventually
word got to the outside world about these efficacious little creatures.
The combination of the metal-rich mineral waters, the fish and mountain
sunlight have been helping psoriasis sufferers ever since. The first
rudimentary spa was built here in the 1950s. The present hotel
buildings, spa pools and changing facilities were built in the 1970s.
There are two open-air and two indoor pools, each home to hundreds of
small fish.
The fish have made a name for themselves as bio-therapists. Members of
the carp and minnow family, the two species of fish in the spa pools
appear to survive the 37 degree water with no ill effects. I ventured
into one of the outdoor spa pools. The fish were hungry after a spring
when few visitors had braved the blood-warm waters while being pelted
by hailstones or snow.
It might sound masochistic but it was suprisingly fun. The normally
vegetarian fish homed in on areas of dry skin, around my heels and,
particularly ticklish, the soles of my feet. But for a psoriasis
sufferer, the fish target the plaques - areas of sore, red and
thickened skin. The more benign beasts, the "lickers", rarely
exceed a couple of inches in length. They cruise their way along the
surface of your skin, gently scraping off and munching loose skin
flakes. Less gentle are the aptly named "strikers", who employ more
of a hit-and-run mechanism. Very fast, they dart in, take a chunk out
of you and swim off to enjoy their spoils at leisure.
According to the British Association of Dermatologists, this removal of
superfluous skin flakes aids sufferers because "it may help topical
medications to penetrate, which is why some people may notice some
improvement, but we are not aware of any other proven benefits".
The psoriasis treatment regimen is not for the fainthearted. Twenty-one
days of twice- daily, four-hour bathing sessions in the fish pools is
prescribed, plus drinking 1.5 litres of spa water a day on an empty
stomach. However, many of the guests saw a major improvement in their
skin condition during the treatment.
Paul 36, from Northern Ireland, has had psoriasis since the age of 14.
"I've tried steroid creams, Chinese herbs, acupuncture, you name
it." But he felt the spa did make a difference. "I definitely saw
an improvement in my skin, but it's hard to say whether it's the
water or the fish." Personally speaking, I have an idea that there
are easier ways to exfoliate my feet, but probably none half as much
fun.
# Balikli Kaplica Spa, Kangal, Sivas, Turkey 00 90 346 469 1151/53/54
Ambience
Accommodation is basic but clean - think 1970s youth hostel. The
public areas in the hotel are smoke-filled, particularly the television
room in the evenings, where Turkish guests meet to play cards and
dominoes. Bring a DVD player, iPod and books.
Quality of experience
Good, although the fish spa pools are the only game in town, and the
only "therapist" other than the fish is an onsite nurse who
doesn't speak English, although the manager can translate.
Food
Tasty local meals - lots of aubergine dishes, fresh tomato salads and
local lamb.
In-crowd
The hotel caters for people who are willing to try anything to tackle
their psoriasis. Repeat visitors come from all over the world.
Wallet watch
$22 (£12) a day full board, plus $50 a day for access to the pools.
Need to know
Turkish Airlines fly via Istanbul to Sivas on Fridays and Sundays:
www.thy.com
=================================================
You can buy some of the little nibblers here,
http://images.google.com/images?svnum=10&hl=en&lr=&q=+Garra+rufa+&btnG=Search
http://www.psoriasisfishcure.com/researches/doctor_fish.htm
Blue Lagoon last week, turkish fish this week. Next week we'll be down
in a hole with NB-uvb's I suPPose.... anyone been to the dead sea
lately?
randall..; don't actually want to go there! Just clear right here!
randall
Haven't seen much on toPic for P the last few days, other
then Mass General getting $186M in settling their enbrel
law suit with amgen,
http://news.google.com/news?hl=en&tab=wn&ie=UTF-8&q=enbrel+Massachusetts+General+Hospital&btnG=Search+News
Yet, who wants to hear about someone getting rich off their P & misery?
Let's go with a potpourri of immune and health related stories instead.
I'll go first, i've gone on alcar, or should I say alpha lipoic acid
100mg.s (not the **racemate or r-ala) and acetyl L-carnitine (500 mgs)
2X day, as a test for the next few days/weeks.
As i've also just started the molasses in my shakes, any improvements
will be
attributed to the alcar as it's much more expensive. lol
**Of or relating to a chemical compound that contains equal quantities
of dextrorotatory and levorotatory forms and therefore does not rotate
the plane of incident polarized light.
This next one is an old nemesis for P....
Alcohol the NEW Medicine?
http://www.signonsandiego.com/uniontrib/20060606/news_1n6alcohol.html
One drink a day for men and one a week for women? Come on!
The only problem with this is one leads to another.
One is good and ten is sin!
And non is zen. And the alternative people brew it in their guts. ;-/
------------------------------------------------------------------------
I wonder were booze fits in with this next abstract?
We know to much alcohol skews us towards a Th1 profile
with high TNF-alpha levels. Exactly what the biologicals block btw.
This next abstract finally puts the finger on inflammation and what
you/we/me stuff in our faces each and every day.
http://www.ajcn.org/cgi/content/abstract/83/6/1369
Dietary patterns are associated with biochemical markers of
inflammation and endothelial activation in the Multi-Ethnic Study of
Atherosclerosis (MESA) 1,2,3
Jennifer A Nettleton, Lyn M Steffen, Elizabeth J Mayer-Davis, Nancy S
Jenny, Rui Jiang, David M Herrington and David R Jacobs, Jr
1 From the Division of Epidemiology and Community Health, School of
Public Health, University of Minnesota, Minneapolis, MN (JAN, LMS, and
DRJ); the Department of Nutrition, University of Oslo, Oslo, Norway
(DRJ); the Center for Research in Nutrition and Health Disparities and
the Department of Epidemiology and Biostatistics, Arnold School of
Public Health, University of South Carolina, Columbia, SC (EJM-D); the
Department of Pathology, University of Vermont, Burlington, VT (NSJ);
the Columbia University, New York, NY (RJ); and the Department of
Public Health Sciences, Wake Forest University, Winston-Salem, NC (DMH)
Background: Dietary patterns may influence cardiovascular disease risk
through effects on inflammation and endothelial activation.
Objective: We examined relations between dietary patterns and markers
of inflammation and endothelial activation.
Design: At baseline, diet (food-frequency questionnaire) and
concentrations of C-reactive protein (CRP), interleukin 6 (IL-6),
homocysteine, soluble intercellular adhesion molecule-1 (sICAM-1), and
soluble E selectin were assessed in 5089 nondiabetic participants in
the Multi-Ethnic Study of Atherosclerosis.
Results: Four dietary patterns were derived by using factor analysis.
The fats and processed meats pattern (fats, oils, processed meats,
fried potatoes, salty snacks, and desserts) was positively associated
with CRP (P for trend < 0.001), IL-6 (P for trend < 0.001), and
homocysteine (P for trend = 0.002). The beans, tomatoes, and refined
grains pattern (beans, tomatoes, refined grains, and high-fat dairy
products) was positively related to sICAM-1 (P for trend = 0.007). In
contrast, the whole grains and fruit pattern (whole grains, fruit,
nuts, and green leafy vegetables) was inversely associated with CRP,
IL-6, homocysteine (P for trend = 0.001), and sICAM-1 (P for trend =
0.034), and the vegetables and fish pattern (fish and dark-yellow,
cruciferous, and other vegetables) was inversely related to IL-6 (P for
trend = 0.009). CRP, IL-6, and homocysteine relations across the fats
and processed meats and whole grains and fruit patterns were
independent of demographics and lifestyle factors and were not modified
by race-ethnicity. CRP and homocysteine relations were independent of
waist circumference.
Conclusions: These results corroborate previous findings that
empirically derived dietary patterns are associated with inflammation
and show that these relations in an ethnically diverse population with
unique dietary habits are similar to findings in more homogeneous
populations.
Key Words: Multi-Ethnic Study of Atherosclerosis · inflammation ·
endothelial activation · dietary patterns · factor analysis
------------------------------------------------------------------
Some herbs can kill you.
http://www.paktribune.com/news/index.php?id=145980
________________________________________
http://www.medicalnewstoday.com/medicalnews.php?newsid=44461&nfid=nl
Gene Therapy Applications Of RNA Interference
----------------------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=44173&nfid=nl
New Pathways For Autoimmune Treatment Identified
Key words: APS1, iNKT, sea plant lipid- alpha-GalCer,
------------------------------------------------------------------------
Ulcers can be wiPPed out with antibiotics. Now, crohn's is going down
the same pathways?
http://www.medicalnewstoday.com/medicalnews.php?newsid=38664
Professor Tom Borody of Sydney, Australia will present the results of
over 20 years of research into an effective treatment for Crohn's
Disease. He will deliver data from a clinical study of 213 patients in
Australia along with the responses to treatment of over 50 of Prof.
Borody's own patients, to his anti-mycobacteria therapy research.
According to Prof. Borody's report, as many as 95% of his patients have
responded to treatment with full remission achieved by 65% of these
patients. Dr. Borody says, "These results exceed all documented
evidence of response to Crohn's Disease therapies and promise
significant relief for a large number of the estimated one million
Crohn's patients around the world."
<sniP>
The same article but written more so for the layman,
http://www.newsday.com/news/health/ny-hscov4742774may16,0,4096487.story?coll=ny-leadhealthnews-headlines
-------------------------------------------------------
If P is a gut thing, then could Ben Blavat's program treating gut and
skin be
the path to the ultimate P cure?
How are you doing Ben? I hope your clear and reading this.
------------------------------------------------------
If your an alien from outer space and you'd like the directions to make
a human bean,
step right up.
http://www.nature.com/nature/supplements/collections/humangenome/index.html
http://genome.wellcome.ac.uk/
I wonder how many folks will get the bluePrints on themselves?
I wonder if I will?
---------------------------------------------------
http://news.biocompare.com/newsstory.asp?id=138031
Natural Born Killers
6/5/2006
Source: Salk Institute
A collaboration between scientists at the Salk Institute for Biological
Studies and the Pasteur Institute in Paris has uncovered the molecular
signals that trigger maturation of natural killer cells, an important
group of immune system cells, into fully armed killing machines. Their
findings will be published in a forthcoming issue of Nature Immunology.
Born to kill, natural killer cells are constantly on the prowl for
potentially dangerous invaders, ready to unleash their deadly arsenal
at a moment's notice. Prior to the study, scientists were familiar with
the diverse repertoire of surface molecules that helps natural killer
cells distinguish friend from foe, but how they acquired their
reconnaissance tool kit had remained unclear.
"We suspected that an environmental signal triggered the
differentiation of immature natural killer cells into cells that could
recognize and kill invading pathogens," says one of the senior authors,
Greg Lemke, Ph.D., a professor in the Salk's Molecular Neurobiology
Laboratory, "but we didn't know what it was."
When co-senior author Claude Roth, Ph.D., an immunologist at the
Institut Pasteur, discovered that low levels of a protein called Axl,
which belongs to a class of molecules collectively known as receptor
tyrosine kinases, correlated with diminished killer activity in natural
killer cells, he turned to Lemke.
Lemke's lab had studied the effects of deleting or "knocking out" the
Axl gene and its two cousins Mer and Tyro3, sometimes referred to as
the Tyro3 family, for over a decade. Although the Salk scientists had
been initially interested in how a missing Tyro3 protein impacted brain
development, they found that mice lacking all three Tyro3 genes
developed autoimmune diseases closely resembling the perplexing
symptoms observed in human autoimmunity.
According to Lemke, they couldn't help noticing that the Tyro3
"knock-out" animals were very sick and prone to infections, which -
now that we know that their natural killers were compromised - makes
perfect sense. As part of the innate arm of the immune system, natural
killer cells are the body's immediate line of defense, keeping invaders
in check until T and B cells of the immune system, which take a few
days to mobilize, kick into full gear.
Natural killer cells are armed with enzyme-filled sacs that spill their
deadly contents when infected or cancerous cells cross the killer's
path. In addition, they secrete cytokines, chemical messengers that
jumpstart the T and B cell response.
What the Salk and Pasteur teams discovered is that when all three Tyro3
proteins are missing, natural killer cells are still armed with their
arsenal of enzymes and cytokines, but they can't dip into their weapons
cache because they lack the full spectrum of surface molecules that
gives them the "license to kill".
"From these data it was clear that Tyro3 receptor kinases transmit the
environmental signals, which we knew are crucial for the maturation of
precursor cells," says Lemke. Receptor tyrosine kinases normally
receive signals from a cell's environment and, upon activation, add a
phosphate group to intracellular proteins, initiating a new repertoire
of cellular behaviors.
For natural killer cells those signals - two well-established ligands
of Tyro3 proteins called Gas6 and protein S - are secreted by bone
marrow stromal cells, which form the local support network for natural
killer cell precursors constantly generated in the bone marrow. As the
immature natural killer cells get ready to move out of the bone marrow,
stromal cells give them the go ahead to acquire the full spectrum of
surface receptors, allowing them to attack with discrimination rather
than raw determination.
<sniP>
__________________________________________________
Interesting Aids story going back 25 years in the eyes of an
immunologist.
http://www.dailybruin.ucla.edu/news/articles.asp?id=37502
------------------------------------------------------------------
A new vaccination. Is it for the Birds?
http://www.merckmedicus.com/pp/us/hcp/hcp_newsarticle.jsp?newsid=658103&newsgroup=2
------------------------------------------------------------------
Sugarbiology (aka- glycobiology)
http://www.medicalnewstoday.com/medicalnews.php?newsid=44430&nfid=nl
----------------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=44236&nfid=nl
Increasing Interest In Cholesterol-Lowering Treatment Drive Phytosterol
Sales
---------------------------------------------------------------
Naltrexone for crohns,
http://www.medicalnewstoday.com/medicalnews.php?newsid=44162&nfid=nl
-------------------------------------------------------------------
Ulcer bacteria burrowing secrets
http://www.medicalnewstoday.com/medicalnews.php?newsid=44196&nfid=nl
_______________________________________
Colon genome,
http://www.medicalnewstoday.com/medicalnews.php?newsid=44422&nfid=nl
For the first time, scientists have defined the collective genome of
the human gut, or colon. Up to 100 trillion microbes, representing more
than 1,000 species, make up a motley "microbiome" that allows humans to
digest much of what we eat, including some vitamins, sugars, and fiber.
In a study published in the June 2 issue of Science, scientists at The
Institute for Genomic Research (TIGR) and their colleagues describe and
analyze the colon microbiome, which includes more than 60,000
genes--twice as many as found in the human genome. Some of these
microbial genes code for enzymes that humans need to digest food,
suggesting that bacteria in the colon co-evolved with their human host,
to mutual benefit.
"The GI tract has the most abundant, diverse population of bacteria in
the human body," remarks lead author Steven Gill, a molecular biologist
formerly at TIGR and now at the State University of New York in
Buffalo. "We're entirely dependent on this microbial population for our
well-being. A shift within this population, often leading to the
absence or presence of beneficial microbes, can trigger defects in
metabolism and development of diseases such as inflammatory bowel
disease."
As in studies of other animals, the scientists began by collecting
droppings. They collected fecal samples from two anonymous, healthy
adults who'd gone without antibiotics or other medications for a year
prior to the study. The researchers created DNA libraries based on the
samples, generating a total of 65,059 and 74,462 sequence reads,
respectively, from the two subjects. They found evidence for several
hundred bacterial phylotypes, most falling into two divisions of
bacteria known as Firmicutes and Actinobacteria. In addition, a
microbial organism known as a methanogenic archaeon, Methanobrevibacter
smithii, was prominent.
To assess the diversity of the colon microbiome, the researchers used
two strategies. First, they matched their gut microbial DNA sequences
up to two databases, one containing 16s rDNA gene sequences and the
other containing non-redundant protein sequences. Second, they compared
the colon-culled sequences to two previously sequenced human gut
organisms: a bacterium, Bifidobacterium longum, and the archaeal
microbe M. smithii. These known organisms showed striking similarity to
much of the microbiome residents.
Based on the sequence comparisons, the researchers conclude that the
human GI tract hosts multiple strains of B. longum, and a majority of
its archaeal species is related M. smithii. How many unique bacterial
genera or species exist in the colon community? By comparison to the
outside world, Gill suspects the human gut is at least as complex as
our soils or seas. With the evidence at hand, the researchers have
described greater diversity in the human gut than researchers have
reported for samples of acid mine drainage.
These microbes are busy, too. The new study shows that resident
microbes in the colon actively synthesize vitamins and break down plant
sugars, such as xylan and cellobiose (similar to cellulose), which
humans could not otherwise digest because we lack the necessary
enzymes. Cellobiose, for instance, is a key component of plant cell
walls and thus is found in most edible plants, such as apples and
carrots.
The new study advances the growing field of metagenomics, or the study
of many genomes found in a given ecosystem. Scientists at TIGR and
elsewhere have recently scooped up whole environmental samples, from
soil to sea, to study the diverse genomes contained within them. The
idea is to survey a complex community in one fell swoop, examining how
whole ecosystems of genomes respond to environmental
perturbations--and, in the case of humans, how microbial ecosystems
contribute to health and disease.
"This study is an important first step toward identifying microbial
differences between healthy people and those with conditions ranging
from Crohn's Disease to cancer," says co-author Karen Nelson of TIGR,
who has previously studied the guts of termites and other animals. "We
might compare different individuals, with different diets, for
instance."
More broadly, the new work could become the opening salvo of a Human
Microbiome Project that defines the microbial side of ourselves,
suggests co-author Jeffrey Gordon, a microbiologist at Washington
University in St. Louis. Gordon envisions such a project pursuing
fundamental questions. How different are our microbiomes? Should
differences in our microbiomes be viewed, along with our immune and
nervous systems, as features of our biology that are affected by our
individual environmental exposures? How is the human microbiome
evolving as a function of our changing diets, lifestyle, and biosphere?
Finally, how might we alter these microbial communities for better
health in a person or population?
The current study was funded by the Defense Advanced Research Projects
Agency and the Office of Naval Research.
The Institute for Genomic Research is a not-for-profit center dedicated
to deciphering and analyzing genomes. Since 1992, TIGR, based in
Rockville, Md., has been a genomics leader, conducting research
critical to medicine, agriculture, energy, the environment and
biodefense.
Kathryn Brown
kbr...@endpointcreative.biz
The Institute for Genomic Research
http://www.tigr.org
----------------------------------------------------------------------------------
randall... I wonder if the alcar kicked in already?
randall
> I'll go first, i've gone on alcar, or should I say alpha lipoic acid
> 100mg.s (not the **racemate or r-ala) and acetyl L-carnitine (500 mgs)
> 2X day, as a test for the next few days/weeks.
> As i've also just started the molasses in my shakes, any improvements
> will be
> attributed to the alcar as it's much more expensive. lol
>
> **Of or relating to a chemical compound that contains equal quantities
> of dextrorotatory and levorotatory forms and therefore does not rotate
> the plane of incident polarized light.
>
<sniP.
I should have done my alcar due deligence sooner.
So I don't credit the wrong folks i suPPose.
Was Dr. Bruce Ames the man for alcar?
The trail today.
So I was looking alcar patents and found # 5,977,162 with Michael D.
Seidman as the
inventor.
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=4&f=G&l=50&co1=AND&d=PTXT&s1=alcar&s2=lipoic&OS=alcar+AND+lipoic&RS=alcar+AND+lipoic
Where did Bruce Ames go?
http://www.tinnitusformula.com/infocenter/articles/people/seidman_bio.aspx
His anti-aging formula,
http://www.tinnitusformula.com/detail.aspx?ID=11
Nathan D. Hamilton for Juvenon didn't get his alcar patent till 2002? I
thought
Ames was first to get this patent, but i see that isn't so with Seidman
having
gotten one in 1999?
Ok, i see Hamilton is an angel $$ bag man for Ames,
http://www.aspirabio.com/1.1_management.html
And his $$ made him the CEO for Juvenon,
http://www.juvenon.com/about/management.htm
I wonder how much ALCAR he eats every day? What suPPlements does he
take with it?
How many patents does he have for alcar? I see two,
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=0&f=S&l=50&TERM1=alcar&FIELD1=&co1=AND&TERM2=hamilton&FIELD2=&d=PTXT
I wonder now how many patents there are for lipoic acid and carnitine?
Hey look. Here's a patent for dr. ames for stabilizing R-alpha lipoic
acid (r-ala) with nicotinamide,
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=8&f=G&l=50&co1=AND&d=PTXT&s1=carnitine&s2=%22lipoic+acid%22&OS=carnitine+AND+%22lipoic+acid%22&RS=carnitine+AND+%22lipoic+acid%22
Hey Cruiser toss in the nicotinamide for grins!
------------------------------------------
Ifn may be the stuff for some of us to turn off instead of blocking
TNf-alpha.
IFN and P abstract,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16713975
Pro- and Antiinflammatory Cytokine Signaling: Reciprocal Antagonism
Regulates Interferon-gamma Production by Human Natural Killer Cells.
Yu J, Wei M, Becknell B, Trotta R, Liu S, Boyd Z, Jaung MS, Blaser BW,
Sun J, Benson DM Jr, Mao H, Yokohama A, Bhatt D, Shen L, Davuluri R,
Weinstein M, Marcucci G, Caligiuri MA.
Department of Molecular Virology, Immunology, and Medical Genetics, The
Ohio State University College of Medicine and School of Public Health,
Columbus, Ohio 43210.
Activated monocytes produce proinflammatory cytokines (monokines) such
as interleukin (IL)-12, IL-15, and IL-18 for induction of
interferon-gamma (IFN-gamma) by natural killer (NK) cells. NK cells
provide the antiinflammatory cytokine transforming growth factor
(TGF)-beta, an autocrine/negative regulator of IFN-gamma. The ability
of one signaling pathway to prevail over the other is likely important
in controlling IFN-gamma for the purposes of infection and
autoimmunity, but the molecular mechanism(s) of how this
counterregulation occurs is unknown. Here we show that in isolated
human NK cells, proinflammatory monokines antagonize antiinflammatory
TGF-beta signaling by downregulating the expression of the TGF-beta
type II receptor, and its signaling intermediates SMAD2 and SMAD3. In
contrast, TGF-beta utilizes SMAD2, SMAD3, and SMAD4 to suppress
IFN-gamma and T-BET, a positive regulator of IFN-gamma. Indeed,
activated NK cells from Smad3(-/-) mice produce more IFN-gamma in vivo
than NK cells from wild-type mice. Collectively, our data suggest that
pro- and antiinflammatory cytokine signaling reciprocally antagonize
each other in an effort to prevail in the regulation of NK cell
IFN-gamma production.
PMID: 16713975
>
> randall... I wonder if the alcar kicked in already?
randall... i've only taken this stuff 3X's so far and postings have
gone up 200%?
randall
Working on the same theme of nutrition for P. As in last few posts.
More patents from folks who think like us?
The latest and greatest alcar with many turbo ingredients, (inventor :
Rath)
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=carnitine&s2=%22lipoic+acid%22&OS=carnitine+AND+%22lipoic+acid%22&RS=(carnitine+AND+%22lipoic+acid%22)
Dr. Matthias Rath and books against the pharmO industry, (you can read
all of these for free!)
http://www4.dr-rath-foundation.org/THE_FOUNDATION/About_Dr_Matthias_Rath/other_literature.htm
This doctor dude must be in to nutrition big time! He gives his books
away for free.. I'm imPressed.
And after only three doses of alcar i feel like i found Uwe's magic
supplements...
And that's totally cool...
randall..
randall
P News from around the world.
A gene responsible for inflammation! Hot off the presses. Err, only
30 minutes since I saw it on google news.
http://physician-assistant.advanceweb.com/common/Editorial/Editorial.aspx?CC=72052
New Clue to Inflammation
By Nicole Benkert
Scientists continue to strive to understand triggers for inflammation,
and research published last year in Nature Genetics (Curran JE, Jowett
JB, Elliot KS, et al. Genetic variation in selenoprotein S influences
inflammatory response. 2005;37(11):1234-1241) may provide further clues
that may help in disease treatment.
Discovering the Gene
An international team of researchers linked Selenoprotein S (SEPS1)
with less inflammation in the cells. It appears that SEPS1 helps clear
the build-up of misfolded proteins when cells are stressed, according
to a press release from the Medical College of Wisconsin. However,
people with a rarer variation in this gene don't clear out these bad
proteins as easily and suffer higher levels of inflammation.
By isolating this gene, researchers may be able to develop drugs that
specifically regulate the SEPS1. They are also curious about learning
more about this gene and disease susceptibility - since inflammation
plays a role in nearly every disease process.
Studying the Gene
Study designer John Blangero, PhD, and colleagues at the Southwest
Foundation for Biomedical Research in San Antonio, showed that a
variant in the gene's promoter region - which regulates SPES1
expression - was present in people with the highest levels of
inflammation.
The study found the same relationship between SEPS1 and inflammation in
two geographically and ethnically distinct populations of people in the
United States, one in Wisconsin and one in Texas. <sniP>
http://www.chinadaily.com.cn/sports/2006-06/09/content_613278.htm
Beijing's dramastic fall a concern for Olympics
By Xiao Guo (chinadaily.com.cn)
Updated: 2006-06-09 16:27 Beijing came in second to last place in a
survey ranking cities around the country on living conditions,
according to a China Business Times report, raising concerns about
Beijing's preparedness for the 2008 Olympic Games.
In 2005, Beijing placed 15th, falling from 4th place in 2004. The
survey, organized by a local consultant company, collected data from
2,553 participants from 20 cities across the country.
Beijing, the city slated to host the 2008 summer Olympic games, also
placed second overall behind Tianjin in a separate survey that measured
people's perceptions of a city's general sophistication and resident's
general manners and behavior. Survey respondents evaluated such
behavior as spitting in the street, rude speech, cutting in line and
visible advertisements.
Advertisements, such as billboards and illegally posted papers on city
property and roads are branded as _______'city psoriasis'_______ in
China. Beijing is plagued by the ________'disease',________ which
_____tarnishes____ the city's image.
According to a Xinhua News Agency report, the local municipality is
stepping up efforts to clamp down on those posting the ubiquitous
advertisements, but there are no effective measures in place to fight
the misconduct so far.
Large cities such as Shanghai, Guangzhou and Tianjin also scored badly
on the surveys.
Experts say the listings indicate that although big cities mean more
development and opportunities for citizens, they score low in living
and housing conditions as well as in environment and transportation.
------------------------------------------------------------------------------
Is china a big P place or what? I thought that the asian continent was
about 1% and
mainly late onset, like Japan for instance. Same with the middle east?
Ok. Here's a chinese p site,
http://www.hkmj.org.hk/skin/psoriasi.htm
[...]
There had been analysis in the figure of some local dermatology clinics
of Social Hygiene Service in 1974 to 1976 and comparison with some of
the larger cities in China, Taiwan and Japan claiming the number of
psoriasis in the Mongoloid race to be around 0.3% or well below
1%.<sniP>
Did it go uP % wise in the last few decades? Or are the psoriasis signs
designed
to scare folks away?
Here's a link for those wishing to research it,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=PubMed&term=psoriasis+china&tool=QuerySuggestion
-----------------------------------------------------------------------------
Maybe what they/you/me need is that old time religion? How's your
faith?
http://www.naplesnews.com/news/2006/jun/09/joeartist/?neapolitan
[...]
"I believe she saved my life," he says quietly, looking down with
reverence.
[...]
Izzillo first learned about Kateri 35 years ago when he was on vacation
in Montreal and read about a high Mass that took place each Sunday at
the Mohawk reservation there. He attended one and learned more about
her.
"She was known for wandering into the woods saying the rosary and
carving crosses in trees," Izzillo explains. "When Kateri died, the
pock marks disappeared from her body and a Jesuit said that was the
moment when she entered the gates of heaven."
At the time Izzillo was battling a debilitating case of
__-psoriasis.___ The skin disease looked to him like leprosy, and the
scaly red patches caused him so much pain he had trouble sleeping.
After attending the Mass, Izzillo says his psoriasis went away. He
considers that a miracle. Gone too was the depression that came along
with the disease.
Since then, he's worked tirelessly to get the Catholic Church to make
his savior a saint.
<sniP>
----------------------------------------------------------
>From Mumbai, mumbo jumbo.
http://www.thehindubusinessline.com/life/2006/06/09/stories/2006060900150300.htm
[...]
Dr Malathi claims that even those suffering from cancer, kidney
problems and psoriasis have responded positively to hypnotherapy.
<sniP>
-----------------------------------------------------------
randall... oPening game of fifa world cuP: germany 4 costa rica 2
randall
P news from around the world.
http://www.dallasnews.com/sharedcontent/dws/bus/columnists/chall/stories/DN-Hall_11bus.ART0.State.Edition1.9046d78.html
[...]
Bill Kling of Swiss-American Products has just taken his Elta Crème,
well-known in medical settings, to the mass market, including CVS and
Kroger stores.
[...]
Elta Crème, Swiss-American's signature product, originates from a
grease used in Switzerland on the udders of milk cows. In 1987, Mr.
Kling transformed it into a super moisturizer for humans to treat
severe dry skin associated with diabetes, psoriasis and eczema.
The cream, which is really more of an ointment, is waterproof,
water-free, hypoallergenic, sensitivity-, fragrance- and
preservative-free - all vital for diabetics, burn victims and other
people with fragile skin. Half of the nation's burn centers, including
Presbyterian Hospital of Dallas, treat patients with it, Mr. Kling
says. <sniP>
------------------------------------------------------
H'mm, you can find this creme on the web.
http://www.google.com/search?hl=en&q=Elta+Cr%C3%A8me&btnG=Google+Search
-------------------------------------------------------
Any P'sters out there with OCD? Guess what! Your not nuts after all.
http://www.upi.com/HealthBusiness/view.php?StoryID=20060608-032230-8493r
Six genes linked to OCD -- study
WASHINGTON, June 8 (UPI) -- Scientists at Johns Hopkins have found six
genes they think are connected to Obsessive-Compulsive Disorder.
Researchers Yin Yao Shugart and Jack Samuels collected blood samples
from 1,008 individuals from a total of 219 families in which at least
two siblings were clinically diagnosed with OCD.
DNA from each sample was analyzed at the Hopkins Center for Inherited
Disease Research using molecular biology and statistical analysis
computer programs.
Six specific DNA sequences were found more frequently in the DNA of
people with OCD: one each on chromosomes 1, 7, 6 and 15 and two on
chromosome 3.
The researchers said they believe these genes don't cause OCD directly,
but increase the risk for it in conjunction with other genes or
environmental factors.
"OCD once was thought to be primarily psychological in origin," Shugart
told the press, "but now there is growing evidence that there is a
genetic basis behind (it) that will help us better understand the
condition."
According to the authors, OCD is characterized by repetitive, illogical
thoughts that do not go away, called obsessions, and repetitive,
illogical behaviors, such as constant hand washing, called compulsions.
The condition affects approximately three percent of the American
population.
The researchers published their findings in the June 6 online issue of
Molecular Psychiatry.
--------------------------------------------------
This next one is so important I'm posting it twice.
If your gut bug's aren't nice then you should know
what precautions to take to avoid downstream ill consequences.
http://www.news-medical.net/?id=18332
First analysis of the genes of a community of human microbes
Researchers have completed the first analysis of the genes of a
community of human microbes, an accomplishment that has far-reaching
implications for clinical diagnosis and treatment of many human
diseases.
Results of the analysis, conducted by a team headed by UB
microbiologist Steven R. Gill, Ph.D., appear in the journal Science.
Gill, who conducted the research while at The Institute for Genomic
Research (TIGR) with colleagues from TIGR, Stanford University and
Washington University, analyzed the DNA of microbes in the human distal
gut as a "community-of-the whole" -- the next frontier in the field of
genetic research called metagenomics.
"The human genome is an amalgam of human genes and the genes of our
microbial 'selves,'" said Gill. "Without understanding the interactions
between our human and microbial genomes, it is impossible to obtain a
complete picture of our biology.
The human genome lacks some essential enzymes that break down the food
we eat into energy essential for survival, a situation which prompts
Gill to note out that while bacteria could survive perfectly well
without their human hosts, humans would be doomed without their
bacterial partners.
"The ultimate goal of the work," he said, "is to develop tools for
clinicians to use in treating disease. With this kind of knowledge, we
can use biomarkers to identify the bacterial population of the
individual. Clinicians then can adjust the population of bacteria to
make that person well. Such an analysis also would determine which
bacteria are resistant to which antibiotics, and help determine the
proper drug to administer.
In the future, healthy individuals could undergo a metagenomic analysis
of their gut to determine their immune status and susceptibility to
certain diseases, Gill said.
Jeffrey I. Gordon, M.D., a major contributor to the research from the
Center for Genome Sciences at Washington University, noted that this
gut "microbiome" project is an important starting point for developing
new drugs for 21st-century medicine.
"Our microbial partners have undoubtedly developed the capacity to
synthesize novel chemical compounds that help establish and sustain
their mutually beneficial relationships with us," said Gordon.
"Prospecting for these 'natural products' and characterizing the
pathways through which they operate should provide new insights into
the function of many of our human genes, new ways for defining our
health, new ways for identifying impending or fully manifest diseases,
plus new treatment strategies."
Although scientists have published metagenomic analyses of samples from
other environments, including soil and the Sargasso Sea, this is the
first publication of an analysis of human-residing organisms. The
researchers chose to investigate the colonic microbiome because fecal
samples are readily accessible, because the human gastrointestinal
tract is the most densely populated microbial community in the body,
and because these microbes perform many critical functions.
Samples for the analysis were derived from two unidentified
individuals. The researchers know only that one is male and one is
female; one is a vegetarian, one is not. Both contributors had received
no antibiotics during the past year, insuring that their population of
intestinal flora was "normal" and stable.
Metagenomic analysis of the two microbial communities for their
potential to carry out necessary functions of human metabolism showed
that both had ample concentrations of essential bacteria, but
comparison of the two identified significant differences.
One subject was "enriched" -- host to more bacteria of a given category
than expected -- for energy production and conversion, carbohydrate
transport and metabolism, amino acid transport and metabolism and
several other functions.
"This metagenomics analysis begins to define the gene content and
encoded functional attributes of the gut microbiome in healthy humans,"
stated Gill. "In the future we hope to assess the effects of age, diet
and diseases such as IBS, cancer and obesity in the microbial community
of the distal gut in people living in different environments."
Sampling the gut microbiome periodically, as well as those of other
sites, such as the mouth and skin, may allow scientists to determine
the effects of environmental change on our "microevolution," said Gill.
Additional authors on the paper are Robert T. DeBoy, Claire M.
Fraser-Liggett and Karen E. Nelson from TIGR; Mihai Pop from University
of Maryland; Paul B. Eckburg and David A. Relman from Stanford
University; and Peter Turnbaugh and Buck S. Samuel from Washington
University.
--------------------------------------------------------
Find your genetic ancestors. Not a bad project for psoriatics.
http://www.nytimes.com/2006/06/11/weekinreview/11harmon.html
----------------------------------------------------------
A fix for tyPe I diabletes on the horizon.
http://www.hindu.com/thehindu/holnus/008200606050310.htm
[...]
This press release issued by Eurekalert says that more than 7,00,000
Americans have type 1 diabetes, an autoimmune disorder, in which the
body errantly attacks the cells of the insulin-producing cells of the
pancreas, causing chronic hyperglycemia and complications such as
blindness, kidney failure, heart disease and nerve damage.
Previously known as juvenile diabetes, type 1 diabetes is usually
diagnosed at a very early age but is sometimes not diagnosed until the
individual reaches adulthood.
In this study, the Pitt researchers used a gene-delivery vehicle known
as an adeno-associated virus to insert genes for either of two
cytokines, interleukin-4 (IL-4) or interleukin-10 (IL-10), into the
insulin-producing beta cells of non-obese diabetic (NOD) mice.
Following gene delivery, expression of IL-4 in beta cells prevented the
onset of hyperglycemia in NOD mice, whereas beta cell expression of
IL-10 accelerated the onset of hyperglycemia. <sniP>
-----------------------------------------------
An aPPle a day helps against TNF-alpha
http://www.forbes.com/forbeslife/health/feeds/hscout/2006/06/09/hscout533144.html
Apples May Be Heart-Healthy
06.09.06, 12:00 AM ET
FRIDAY, June 9 (HealthDay News) -- New research suggests there may be
truth behind the old adage, "An apple a day keeps the doctor away."
Scientists from the University of California, Davis School of Medicine,
say they've discovered that apples rich with compounds called
flavonoids help ward off debilitating cell diseases, such as heart
disease and age-related cancers.
The research was funded by the U.S. Apple Association and the Apple
Products Research and Education Council.
Studies in the past have found that flavonoids act as antioxidants --
enzymes that target free radicals that can damage DNA. Flavonoids are
commonly found in chocolate, green tea and other fruits and vegetables.
In a prepared statement, Eric Gershwin, a UC-Davis professor of
allergy, rheumatology and immunology, said, "Our study showed that the
flavonoids in apples and apple juice can inhibit signals in this
pathway that would otherwise damage or kill cells in the body."
Gershwin and his colleagues created an apple mash from different apple
varieties, and then exposed the extract to endothelial cells, which
line blood vessels. Then they exposed the cells to tumor necrosis
factor (TNF), a compound that promotes inflammation and can trigger
cell death.
The apple extract preserved and protected the cells by hindering
communication between them.
The study results appear in the current issue of Experimental Biology
and Medicine.
More information
For more information on flavonoids, visit
http://lpi.oregonstate.edu/f-w00/flavonoid.html
Key words: * Quercetin (a flavonol in vegetables, fruit skins,
onions)
* Xanthohumol (a prenylated chalcone in hops and beer)
* Isoxanthohumol (a prenylated flavanone in hops and beer)
* Genistein (an isoflavone in soy)
Pro-oxidant flavonoids
* Chalconaringenin (a non-prenylated chalcone in citrus fruits)
* Naringenin (a non-prenylated flavanone in citrus fruits)
---------------------------------------------------------------------------------------
http://www.ajcn.org/cgi/content/abstract/83/6/S1520
Supplement: n-3 Fatty Acids: Recommendations for Therapeutics and
Prevention
n-3 Fatty acids and gene expression1,2,3,4
Richard J Deckelbaum, Tilla S Worgall and Toru Seo
1 From the Institute of Human Nutrition (RJD, TSW, and TS), the
Department of Pediatrics (RJD, TSW, and TS), and the Department of
Pathology (TSW), College of Physicians & Surgeons of Columbia
University, New York, NY
ABSTRACT
Accumulating evidence in both humans and animal models clearly
indicates that a group of very-long-chain polyunsaturated fatty acids,
the n-3 fatty acids (or omega-3), have distinct and important
bioactive properties compared with other groups of fatty acids. n-3
Fatty acids are known to reduce many risk factors associated with
several diseases, such as cardiovascular diseases, diabetes, and
cancer. The mechanisms whereby n-3 fatty acids affect gene expression
are complex and involve multiple processes. As examples, n-3 fatty
acids regulate 2 groups of transcription factors, such as
sterol-regulatory-element binding proteins and peroxisome
proliferator-activated receptors, that are critical for modulating the
expression of genes controlling both systemic and tissue-specific lipid
homeostasis. Modulation of specific genes by n-3 fatty acids and
cross-talk between these genes are responsible for many effects of
n-3 fatty acids.
--------------------------------------------
Well Then! How much n-3 a day does a normal person need, let alone a
psoriatic?
http://www.ajcn.org/cgi/content/abstract/83/6/S1483
Healthy intakes of n-3 and n-6 fatty acids: estimations considering
worldwide diversity1,2,3,4,5
Joseph R Hibbeln, Levi RG Nieminen, Tanya L Blasbalg, Jessica A Riggs
and William EM Lands
1 From the Laboratory of Membrane Biochemistry and Biophysics and the
National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, Bethesda, MD
ABSTRACT
Background: The worldwide diversity of dietary intakes of n-6 and
n-3 fatty acids influences tissue compositions of n-3 long-chain
fatty acids (LCFAs: eicosapentaenoic, docosapentaenoic, and
docosahexaenoic acids) and risks of cardiovascular and mental
illnesses.
Objective: We aimed to estimate healthy dietary allowances for n-3
LCFAs that would meet the nutrient requirements of 97-98% of the
population.
Design: Deficiency in n-3 LCFAs was defined as attributable risk from
13 morbidity and mortality outcomes, including all causes, coronary
heart disease, stroke, cardiovascular disease, homicide, bipolar
disorder, and major and postpartum depressions. Dietary availability of
n-3 LCFAs from commodities for 38 countries and tissue composition
data were correlated by best fit to each illness in deficiency risk
models.
Results: The potential attributable burden of disease ranged from 20.8%
(all-cause mortality in men) to 99.9% (bipolar disorder). n-3 LCFA
intake for Japan (0.37% of energy, or 750 mg/d) met criteria for
uniformly protecting >98% of the populations worldwide. n-3 LCFA
intakes needed to meet a tissue target representative of Japan (60%
n-3 in LCFA) ranged from 278 mg/d (Philippines, with intakes of 0.8%
of energy as linoleate, 0.08% of energy as {alpha}-linolenate, and
0.06% of energy as arachidonic acid) to 3667 mg/d (United States, with
8.91% of energy as linoleate, 1.06% of energy as {alpha}- linolenate,
and 0.08% of energy as arachidonic acid).
Conclusions: With caveats inherent for ecologic, nutrient disappearance
analyses, a healthy dietary allowance for n-3 LCFAs for current US
diets was estimated at 3.5 g/d for a 2000-kcal diet. This allowance for
n-3 LCFAs can likely be reduced to one-tenth of that amount by
consuming fewer n-6 fats.
---------------------------------------------
There you have it! Stop as much n-6 as possible and you need less n-3.
Obtainable
with cod liver oil, fish oil pills, flax seed oil, walnuts, dha/epa
eggs etc.
randall...
randall
When you least expect it, the P news has an actual story that may
just go some where.
>From Israel today:
http://www.israel21c.org/bin/en.jsp?enDispWho=InThePress&enPage=BlankPage&enDisplay=view&enDispWhat=Zone&enZone=InThePress&Date=06/14/06
Psoriasis gene ID'd by Israeli researchers
Jun. 14 - A new gene associated with a variant of psoriasis and
seborrheic dermatitis has been identified by a research group led by
Dr. Ohad Birk at the Morris Kahn Laboratory of Human Genetics at Ben
Gurion University and Soroka Medical Center. The gene discovered by the
Israeli researchers is of much interest as it allows the first major
molecular insight into why the specific skin cells proliferate
excessively, causing these two common skin diseases. Psoriasis and
seborrheic dermatitis affect 2-3% of the population worldwide and 85%
of AIDS patients. Both skin diseases are caused by excessive
proliferation of specific cells (keratinocytes) in the skin. To date,
there is only very limited understanding as to the molecular mechanisms
causing these two common disorders. The two-and-a-half-year study
examined an Israeli Moroccan Jewish family with 44 members over five
generations who showed signs characteristic of psoriasis and seborrheic
dermatitis. By using advanced techniques to analyze DNA samples of the
affected members of the family and comparing them to normal, unmutated
DNA, Ramon Birnbaum, a doctoral student at Birk's laboratory, has
succeeded in pinning the beginning of the molecular pathway on a
mutation in a gene that is normally expressed, or "turned on" in the
keratinocytes. The gene is believed to suppress or regulate cell
proliferation and is thought to be a transcription factor, meaning that
it switches on other genes, which may also play a role in the disease.
When mutated, this regulation malfunctions, enabling excessive
proliferation of skin cells and calling in cells of the immune system.
The findings, to be reported in this month's issue of Nature Genetics,
allow new insights into the mechanism of disease in psoriasis and
seborrheic dermatitis. In turn, these insights are likely to assist
pharmaceutical companies in developing "smart drugs" for these two
common skin diseases.
------------------------------------------------
By smart, do they mean smarter then biologics and therefore costlier?
The opposite would be nice. But if they had a drug that cured us, the
money pipeline would be shut off.
At least it will be fun to understand these new pathways.
-------------------------------------------------
Il-18 abstract from Poland.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16766395
Plasma and scales levels of interleukin 18 in comparison with other
possible clinical and laboratory biomarkers of psoriasis activity.
Flisiak I, Klepacki A, Chodynicka B.
Department of Dermatology and Venereology, Medical University of
Bialystok, Bialystok, Poland.
The aim of the study was to assess plasma and scales levels of
interleukin (IL) 18 collected from psoriatic patients with different
disease activity. IL-18 concentrations were measured using an enzyme
immunoassay in the plasma and scales of 34 patients with chronic plaque
type psoriasis. IL-18 levels were analysed with respect to
plasma-transforming growth factor beta1 (TGF-beta1), the disease
duration and the duration of the present relapse, and psoriasis area
and severity index (PASI). Plasma IL-18 concentration varied from 90 to
1300 pg ml-1 and means (368.2+/-42.4 pg ml-1) were significantly
elevated in comparison with healthy controls (205.9+/-31.8 pg ml-1).
The presence of IL-18 was also demonstrated in scales from skin
lesions. Treatment caused a significant decrease of plasma IL-18
concentration to 250.2+/-13.8 pg ml-1. There was a significant
correlation between plasma IL-18 levels and PASI values (r=0.554).
There was no correlation between IL-18 concentration in scales and
PASI, between IL-18 concentrations in plasma and scales, and between
plasma IL-18 and the disease duration or duration of present relapse.
Plasma TGF-beta1 concentration demonstrated a significant correlation
with PASI (r=0.353), but not with IL-18 levels in plasma (r=0.063) and
scales (0.141). The sum of plasma levels of IL-18 and TGF-beta1 divided
by the optimal coefficient demonstrated a statistically significant
correlation with the highest r-value. The findings confirm an
association between plasma IL-18 concentration and psoriasis severity.
Moreover, it was shown that combined measurement of IL-18 and TGF-beta1
in plasma can be considered as a possible biomarker of psoriasis
activity.
PMID: 16766395
Ok
Begs the question concerning Tgf-beta1's effects,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20psoriasis+tgf-beta1
That second hit is interesting.
randall... Knowledge is power, bring it on.
randall
The last P news story got me looking around and I found this uPcoming
(aug-2006)
genetics forum in Oz.
http://www.ichg2006.com/
Which lead me to this,
http://www.ichg2006.com/abstract/1107.htm
Autosomal dominant psoriasiform seborrhea-like dermatitis caused by a
mutation in PSORAEL, a novel putative transcription factor
# Mr Ramon Birnbaum, Ben-Gurion University, Israel
# Dr Alex Zvulunov, Schneider Children's Medical Center, Israel
# Dr Dafna Hallel-Halevy, Soroka Medical Center, Israel
# Dr Rivka Ofir, Ben-Gurion University, Israel
# Dr Emanuella Cagnano, Soroka Medical Center, Israel
# Dr Dan Geiger, Technion, Israel
# Ms Yael Feferman, Ben-Gurion University, Israel
# Dr Ohad Birk, Ben-Gurion University and Soroka Medical Center, Israel
Seborrheic dermatitis (SD) and Psoriasis are common chronic
papulosquamous dermatoses. Occasionally, distinction between these
entities can be obscured by overlapping clinical features, particularly
when the manifestations are limited to the scalp and face. Hence, the
term Sebopsoriasis (SP) had been applied in such cases. A Jewish family
of Moroccan descent presented with autosomal dominant psoriasiform
seborrhea-like dermatosis affecting 44 individuals in 5 generations.
Through genome wide linkage analysis we mapped the disease gene to a
0.5cM region (maximum lod score 8.8 at theta=0), within a locus
previously associated with psoriasis. Sequencing of candidate genes
within that locus identified a mutation in a novel putative
transcription factor, we named PSORAEL. The mutation fully abrogates
the putative active domain of the encoded protein. The gene is normally
expressed in keratinocytes but not in fibroblasts, suggesting that the
primary event leading to the disease is in keratinocytes. PSORAEL is
the first gene shown to be associated with SD, and the first gene
associated with mendelian heredity of a non-arthritic variant of
psoriasis.
-----------------------------
The name Psorael seems kinda bougus. Like a cartoon character. No
wonder
the previous story didn't bother to mention it. lol
I bet this will at least explain a HUGE part of the YMMV equation. Look
at Ben Blavat compared to many of us, his P has to have a larger
component
of sebopsoriasis then most here. Not like I haven't said that a few
times already.
Then again, my head P seems to follow Bens skin attack protocols as a
mix
of Th2 and Th1. This may also link to evetsm's condition being a T
helper
cell mix of sorts. And I was befuddled with Th2 atopic skin problems
before
my heavily skewed Th1 psoriasis onset at a young age.
randall..OK i'm scratching my head. Any new thoughts about to PoP out?
>
<sniP>
randall
After yesterday's P gene article, it only makes sense for
more gene things today.
This first article may be able to tell us in live time when the
TNF-alpha is being pumPed out of our cells! That would
be nice to know as it would indict some food or behaviour directly
to the inflammation of P.
http://www.htscreening.net/index.aspx?ID=73173
Chip-Man Technologies Announces Collaboration with TCS CellWorks
Date Posted: Thursday, June 15, 2006
Chip-Man Technologies Limited and TCS CellWorks have announced a
technology collaboration, whereby Chip-Man Technologies' Cell-IQ®
continuous cell culturing platform will be used with TCS CellWorks'
AngioKit model.
Terry Cartwright, CEO, TCS CellWorks commented, "TCS CellWorks produces
information-rich in vitro models based on cultured human cells for drug
discovery and functional analysis."
He continued, "We are delighted with the results obtained in
collaboration with Chip-Man Technologies and their new Cell-IQ cell
analysis system."
"This raises our ability to track cell proliferation, migration and
differentiation within a complex co-culture model to a new level."
Cell-IQ is designed to enable the subtle changes in cellular growth and
tubule formation to be recorded and monitored kinetically.
Juha Korpinen, CEO, Chip-Man Technologies added, "We welcome the
opportunity to work with TCS CellWorks. They have a range of products
to which Cell-IQ will bring additional value."
Cell-IQ is a continuous cell culturing platform, optimized for the
real-time analysis of morphological and physiological events in living
cells, co-cultures, primary cells and monolayer tissue models.
The fully integrated 'machine vision' technology is designed to
control all detection and environmental systems.
As a result the Cell-IQ learns to identify, follow and measure
morphological change in individual cells without traditional labels or
dyes.
TCS CellWorks' AngioKit offers a cell-based system using solely human
cell-lines, for quantitatively assessing both pro- and anti-angiogenic
agents.
The kit is provided in 24-well plate format and is suitable for low
volume screening applications.
Angiogenesis is the multi-step process by which new blood vessels
develop from existing vasculature.
It is the subject of intense research activity at present since the
controlled modulation of angiogenesis offers the possibility of
therapeutic approaches to several important diseases including
cardiovascular disease, arthritic disease, cancer, _psoriasis_ and
diabetic retinopathy.
Further Information: http://www.chipmantech.com
----------------------------------------------------------
Speaking of TNF, a new toPical to bind the P inducing craP.
http://www.pharmalive.com/News/index.cfm?articleid=350042&categoryid=40
PALO ALTO, Calif., June 15, 2006 /PRNewswire/ -- Anacor
Pharmaceuticals, a privately-held pharmaceutical company developing
novel agents for inflammatory and infectious diseases, today announced
promising data from a Phase 2a study of AN0128, a novel topical
anti-inflammatory drug candidate for atopic dermatitis (AD), a disease
affecting approximately 15 million Americans.
[...]
AN0128 inhibits the release of pro-inflammatory cytokines, including
TNFalpha, without affecting the normal immune response. It has
demonstrated potent anti-inflammatory activity in pre-clinical models
of inflammation. This activity gives the compound the potential to
treat a number of diseases. Anacor also has conducted Phase 1/2 trials
of AN0128 in acne and _psoriasis_, and will evaluate further studies in
these indications.
<sniP>
----------------------------------------------------------------------
http://www.nutraingredients-usa.com/news/ng.asp?n=68454-advitech-cothera-psoriasis-dermylex
6/15/2006 - Advitech has secured two-part interim financing totalling
C$350,000 to assist in ongoing commercialisation of its psoriasis
product from sweet whey, Dermylex. The boon for the Canadian company
coincides with the finalisation of its first marketing and distribution
deals, with France's Cothera.
<sniP>
I haven't heard much from the few folks who are testing this for us?
Seeing their tests are going into the UVB rich season called summer,
you'd expect them to be jumPing for joy for at least marginal
clearings.
-----------------------------------------------------------------------
http://www.marketwire.com/mw/release_html_b1?release_id=136066
Study Supports Potential of Micromet's Human Antibody MT203 As Novel
Anti-Inflammatory Treatment
MÜNCHEN, GERMANY -- (MARKET WIRE) -- 06/15/2006 --
Carlsbad, CA - June 15, 2006 - Micromet, Inc. (NASDAQ: MITI), a
transatlantic biopharmaceutical company focused on the development of
antibody-based drugs, reports results of a scientific published in
Molecular Immunology. The study describes one of the first human,
high-affinity IgG1 antibodies potently neutralizing human GM-CSF. The
compoustudy1 nd, designated MT203, was generated by Micromet using
phage display-guided selection and is currently in preclinical
development as a novel treatment for inflammatory and autoimmune
diseases including but not limited to rheumatoid arthritis (RA),
asthma, chronic obstructive pulmonary disease (COPD), multiple
sclerosis (MS) and psoriasis.
Results from in-vitro studies demonstrate that MT203 binds human GM-CSF
with low picomolar affinity and potently prevents GM-CSF-induced
proliferation as well as production of the chemokine IL-8. Moreover,
the human antibody was observed to significantly reduce both the
activation and survival of human eosinophils, which are are involved in
the development of a number of inflammatory lung diseases. MT203
retained full neutralizing activity after 5 days in human serum at
37°C.
"We have designed MT203 to meet the highest industry standards for a
novel cytokine-neutralizing antibody in terms of validated antibody
format, highest potency and stability, lowest possible immunogenicity,
and crossreactivity with non-human primates as is required for safety
studies," Patrick Baeuerle, Chief Scientific Officer of Micromet,
commented. "By neutralizing GM-CSF, we believe we have tapped a novel
pharmaceutical target for the potential treatment of patients with
inflammatory diseases."
GM-CSF was only recently recognized as a key pro-inflammatory cytokine
responsible for the proliferation, activation, and survival of a host
of immune cells, which play pivotal roles in the development and
progression of inflammatory diseases. A significant benefit of
neutralizing GM-CSF has been shown in animal models for RA, MS, COPD,
asthma and psoriasis.
(ok, so copy and paste *human GM-CSF psoriasis* in to the pubmed search
box for 40 hits)
-----------------------------------------------------
Speaking of pubmed, you can use this next link to do the last
suggestion.
Abstracts today,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16773312
Systematic evaluation of association between the microsomal glutathione
S-transferase 2 common variation and psoriasis vulgaris in Chinese
population.
Yang S, Yan KL, Zhang XJ, Xiao FL, Fan X, Gao M, Cui Y, Wang PG, Zhang
GL, Sun LD, Wang ZM, Wang DZ, Zhang KY, Huang W, Liu JJ.
Institute of Dermatology and Department of Dermatology at No.1
Hospital, Anhui Medical University, 69 Meishan Road, Hefei, Anhui,
230032, People's Republic of China.
Several recent studies have demonstrated the possible involvement of
the microsomal glutathione S-transferase 2 (MGST2) gene in the
pathogenesis of psoriasis. The objectives of this work are to determine
whether the genetic polymorphisms of the MGST2 gene were associated
with an increased risk of psoriasis in Chinese patients. We first
characterized the linkage disequilibrium pattern within MGST2 and
identified single-nucleotide polymorphisms (SNPs) for tagging common
genetic variants. Genotype- and haplotype-based analyses were then
performed by genotyping the Tag SNPs in a large-scale sample of cases
and controls. We characterized the linkage disequilibrium pattern
within MGST2 using 12 densely distributed SNPs and identified 6 SNPs
for tagging common genetic variants. We then performed an association
analysis by genotyping the six SNPs in 552 cases and 384 controls, but
none of the genotype- and haplotype-based analyses revealed significant
evidence for association. We also performed family-based association
analysis by genotyping the six SNPs in 95 trios; no evidence for
association was identified. Our comprehensive genetic analysis of MGST2
common variants in a large Chinese sample of psoriasis did not provide
any supporting evidence for MGST2 to be the susceptibility gene within
the PSORS9 locus.
PMID: 16773312
-----------------------------------------------------------------
While the Chinese struck out on glutathione P gene links, this next one
looks much better.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16771479
Discovery of a TNF-alpha Antagonist Using Chondroitin Sulfate
Microarrays.
Tully SE, Rawat M, Hsieh-Wilson LC.
Division of Chemistry and Chemical Engineering and Howard Hughes
Medical Institute, California Institute of Technology, Pasadena,
California 91125.
We report the first example of synthetic chondroitin sulfate (CS)
microarrays to rapidly identify glycosaminoglycan-protein interactions
and probe the specificity of proteins for distinct sulfation sequences.
Using the microarrays, we identify a novel interaction between CS and
TNF-alpha, a proinflammatory cytokine involved in rheumatoid arthritis,
Crohn's disease, and psoriasis. Moreover, we demonstrate that CS-E
tetrasaccharides and polysaccharides enriched in the CS-E sulfation
motif can inhibit the activity of this therapeutically important
cytokine. We anticipate that carbohydrate microarrays will accelerate
our understanding of glycosaminoglycan-protein interactions and the
role of sulfation in modulating physiological and disease states.
PMID: 16771479
This is great! It may explain the boost i've seen with Kirkland's
Glucosamine HcL 1500mg's + Chondroitin sulfate 1200mg's supplement over
the last year.
Recall the hyaluronan (HA) threads,
http://groups.google.com/groups/search?q=hyaluronan+%28HA%29+psoriasis&qt_s=Search
And look at this abstract from 1994, found with a *chondroitin sulfate
ha tnf* pubmed search (3 cites returned),
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8195703
Synthetic polysulfated hyaluronic acid is a potent inhibitor for tumor
necrosis factor production.
Chang NS, Intrieri C, Mattison J, Armand G.
Guthrie Research Institute, Laboratory of Molecular Immunology, Guthrie
Medical Center, Sayre, Pennsylvania 18840.
Based on the premise that naturally occurring glycosaminoglycans could
serve as building blocks for synthesizing nontoxic drugs for
suppression of tumor necrosis factor (TNF) production by inflammatory
cells, we have chemically modified hyaluronic acid (HA) and tested its
effects in blocking TNF-alpha and TNF-beta production in vitro. HA was
chosen mainly for its structural simplicity, nonimmunogenicity, and
readiness for chemical modifications. When HA was chemically
polysulfated to a sulfate/hexosamine molar ratio of 3.9, the sulfated
HAs was shown to be a potent inhibitor of TNF-alpha production in
lipopolysaccharide (LPS)- or interferon-gamma-activated THP-1 cells.
For example, a concentration of HAs as low as 10 ng/ml reduced
TNF-alpha production in LPS-activated THP-1 cells more than 50%,
whereas achieving a similar extent of reduction required 50
micrograms/ml native HA. By decreasing the extent of polysulfation, the
inhibitory effect of HAs on TNF-alpha production was diminished. Other
chemical modifications, including deacetylation, thiolation, or
reduction of the carboxylic groups, could not increase the efficacy of
HA in suppression of TNF-alpha production. Naturally polysulfated
glycosaminoglycans, such as chondroitin sulfates, keratan sulfate,
heparan sulfate, and heparin, failed to inhibit TNF-alpha production.
HAs also restricted TNF-beta (lymphotoxin) secretion in an Epstein-Barr
virus-transformed B cell line, Roha-9, which constitutively produces
TNF-beta. HAs had no inhibitory effect on the proliferation of THP-1 or
Roha-9 cells, which would account for the reduced TNF-alpha or TNF-beta
production. Furthermore, time-course metabolic labeling studies
revealed that HAs could not restrict overall protein synthesis and
secretion in THP-1 cells. However, HAs increased complement C1q
secretion in THP-1 in a dose-dependent manner, but it had no effect on
biosynthesis of complement C1 inhibitor, factor D, and Fc gamma
receptor type II (Fc gamma RII). These results indicate that HA,
selectively restricts the production of TNF-alpha, TNF-beta, and
probably several other protein species.
PMID: 8195703
This is outstanding as it may mean a simple suPPlement could be used to
block tnf-alpha and thereby lower psoriasis. Toss in the active agents
in curcumin
and your looking GOOD for cheaP suPPlements.
What's not to like?
I know. Live to 100 with more quality of life then whatever your
hanging with now..lol
--------------------------------------------------
For those of you wanting to live long enough to see a P cure!
I noticed these links over on the sle group yesterday.
http://www.inform.kz/showarticle.php?lang=eng&id=142614
12.06 / 18:26 Anti-aging molecule discovered
SEOUL. June 12, 2006. KAZINFORM - A team of South Korean scientists on
Sunday claimed to have created a ``cellular fountain of youth,'' or
a small molecule, which enables human cells to avoid aging and dying.
The team, headed by Prof. Kim Tae-kook at the Korea Advanced Institute
of Science and Technology, argued the newly-synthesized molecule, named
CGK733, can even make cells younger; KAZINFORM quotes The Korea Times.
The findings were featured by the Britain-based Nature Chemical Biology
online early today and will be printed as a cover story in the
journal's offline edition early next month.
``All cells face an inevitable death as they age. On this path, cells
became lethargic and in the end stop dividing but we witnessed that
CGK733 can block the process,'' Kim said <sniP>
The abstract to go with this article,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16767085
Small molecule-based reversible reprogramming of cellular lifespan.
Won J, Kim M, Kim N, Ahn JH, Lee WG, Kim SS, Chang KY, Yi YW, Kim TK.
Department of Biological Sciences, Korea Advanced Institute of Science
and Technology, Daejeon 305-701, Korea.
Most somatic cells encounter an inevitable destiny, senescence. Little
progress has been made in identifying small molecules that extend the
finite lifespan of normal human cells. Here we show that the intrinsic
'senescence clock' can be reset in a reversible manner by selective
modulation of the ataxia telangiectasia-mutated (ATM) protein and ATM-
and Rad3-related (ATR) protein with a small molecule, CGK733. This
compound was identified by a high-throughput phenotypic screen with
automated imaging. Employing a magnetic nanoprobe technology,
magnetism-based interaction capture (MAGIC), we identified ATM as the
molecular target of CGK733 from a genome-wide screen. CGK733 inhibits
ATM and ATR kinase activities and blocks their checkpoint signaling
pathways with great selectivity. Consistently, siRNA-mediated knockdown
of ATM and ATR induced the proliferation of senescent cells, although
with lesser efficiency than CGK733. These results might reflect the
specific targeting of the kinase activities of ATM and ATR by CGK733
without affecting any other domains required for cell proliferation.
PMID: 16767085
---------------------------------------------------------------------------
And don't forget an aPPle a day.
http://www.cbc.ca/cp/HealthScout/060609/6060916U.html
[...]
In a prepared statement, Eric Gershwin, a UC-Davis professor of
allergy, rheumatology and immunology, said, "Our study showed that the
flavonoids in apples and apple juice can inhibit signals in this
pathway that would otherwise damage or kill cells in the body."
Gershwin and his colleagues created an apple mash from different apple
varieties, and then exposed the extract to endothelial cells, which
line blood vessels. Then they exposed the cells to tumor necrosis
factor (TNF), a compound that promotes inflammation and can trigger
cell death.
The apple extract preserved and protected the cells by hindering
communication between them. <sniP>
------------------------------------------------------------------
RAndall... wow! The glass is 3/4's FULL...
randall
P news from around the globle.
"It's not just another one-molecule company,"
http://seattletimes.nwsource.com/html/businesstechnology/2003064702_vlst16.html
[...]
VLST is sorting through the gene structures of viruses and using them
to point to human genes that might be able to suppress immune responses
that cause ailments like MS, asthma and lupus.
(and p of course)
Many biotech companies search for useful products one at a time. VLST's
approach is based on an observation that company principals Craig Smith
and Ray Goodwin made while at Immunex, where they worked on the
blockbuster arthritis drug Enbrel: Viruses have genes that suppress the
immune system. Those genes aren't useful as drugs themselves. But they
can be used to find analogous genes in humans that would have a similar
immune-suppressing ability, Gillis said.
<sniP>
*****************************************
http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2006/06/16/DDG0FJEMPG19.DTL
A fixation with John Updike? Yes, but I'm not the only one
John Updike walks slowly, as his wife reminds him, and with a sort of
probing delicacy of one who is wary of causing harm.
The eternally alert chronicler of evergreen American life in small
towns and schoolyards, on ball fields and in bedrooms, is 74. His
biography confirms it, and the evidence, in person, is
_______clear_______.
[...]
Same thing when his wife, Martha, mentioned Updike's ____psoriasis____
backstage. Yes, yes, I wanted to say, when Updike mentioned a favorite
neglected novel of his: I love "A Month of Sundays" myself.
<sniP>
(randall note: is this author being ironic? moronic? or clever?)
Even a clear psoriatic isn't truly CLEAR. Not till we hear the cure
word from
at least 100 of us. lol
*****************************
http://www.signaling-gateway.org/update/updates/200606/nri1862.html
The chemokines CCL3 and CCL4 guide naive CD8+ T cells to sites of
antigen-specific interactions between CD4+ T cells and dendritic cells.
It is clear that antigen-presenting cells, such as dendritic cells
(DCs), are necessary mediators of the help provided by CD4+ T cells to
CD8+ T cells. However, many questions remain regarding how these three
cell types interact and whether such interactions are regulated or
occur randomly. Answers to some of these questions have now been
provided by a study published in Nature showing that naive CD8+ T cells
are actively recruited to sites of antigen-specific interactions
between CD4+ T cells and DCs.
In this study, Castellino et al. set out to test the hypothesis that
CD8+ T cells are actively recruited to DCs that are activated by CD4+ T
cells. When immunocompetent mouse recipients of OT-I T cells and OT-II
T cells (CD8+ and CD4+ T cells that express a T-cell receptor specific
for a peptide consisting of amino-acid residues 257-264 and 323-339
of ovalbumin (OVA), respectively) were immunized with OVA257-264 in
adjuvant on both flanks, equal numbers of OT-I T cells were detected in
both draining lymph nodes. However, if OVA323-339 was administered to
one flank (with either OVA257-264 and adjuvant, or adjuvant alone
being concomitantly administered to both flanks), the accumulation of
OT-I T cells was greater in that draining lymph node than in the
contralateral lymph node.
Furthermore, intravital two-photon microscopy showed that, in the
presence of OT-II T cells, OT-I T cells came into contact with DCs
pulsed with OVA323-339 more often than with unpulsed control DCs.
To investigate whether these observations were indicative of the active
recruitment of CD8+ T cells to DCs that are activated by CD4+ T cells,
the mice were administered antibodies specific for candidate
chemokines. Antibodies specific for CC-chemokine ligand 3 (CCL3) or
CCL4 inhibited the accumulation of OT-I T cells in lymph nodes
containing activated OT-II T cells. Both CD4+ T cells and DCs were
found to produce CCL3 and CCL4 when activated. Consistent with a role
for these chemokines in the recruitment of CD8+ T cells, OT-I T cells
isolated from lymph nodes draining the site of immunization expressed
the receptor for CCL3 and CCL4, CC-chemokine receptor 5 (CCR5), whereas
OT-I T cells from non-draining lymph nodes did not.
Furthermore, Ccr5-/- polyclonal CD8+ T cells did not accumulate in
lymph nodes containing activated CD4+ T cells and (in the presence of
OT-II T cells) contacted DCs presenting OVA323-339 with the same
frequency as they contacted control DCs. Functionally, although
administration of antibodies specific for CCL3 and CCL4 did not prevent
the clonal expansion of OT-I T cells or their acquisition of effector
function, the size and effectiveness of the memory OT-I T-cell
population was markedly reduced.
This study provides clear evidence that the ability of CD4+ T cells to
provide help for the generation of an optimal memory CD8+ T-cell
population is not a result of random cell-cell interactions but is a
highly regulated process.
__________
So we do the search that would make robo poster happy, but not
ecstatic,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=PubMed&term=ovalbumin+psoriasis&tool=QuerySuggestion
And checking the group,
http://groups.google.com/groups/search?q=ovalbumin+psoriasis&qt_s=Search
Not like allergy and P hasn't been looked at 1500+ times,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20psoria*+allergy
----------------------------------------------------------------------
This looks interesting.
http://www.sciencedaily.com/releases/2006/06/060616130748.htm
Preventing Skin Infections: EGF Receptor Activation Prevents Microbes
>From Going More Than Skin Deep
Our skin not only serves as a physical barrier against infection but
skin cells themselves can mount an immune response to kill invading
microbes by producing antimicrobial polypeptides (AMPs). As overt
infection in the skin is a rare event, researchers have theorized that
AMPs must not only help fight infection, but play a role in preventing
infection from developing in the first place.
In a study appearing online on June 15 in advance of print publication
in the July issue of the Journal of Clinical Investigation, Ole
Sorensen and colleagues from Lund University, Sweden, investigated what
triggers AMP production in human skin. Interestingly, they found that
AMPs were produced in human skin after sterile wounding of the skin
surface, illustrating that exposure to invading microbes is not the
sole trigger for the immune response in skin.
The authors went on to show that AMP was produced through activation of
the epidermal growth factor receptor (EGFR), which is known to play a
role in the normal wound-healing process. The authors found that the
antibacterial activity of the skin against the potential skin pathogen
Staphylococcus aureus was increased by activation of EGFR, and that the
concentrations of AMPs in the epidermis of wounded skin exceeded those
necessary to suppress or prevent the growth of foreign microbes.
The results of this study demonstrate that wounding of the skin alone,
without the presence of microbes, is sufficient to activate defense
mechanisms in the skin that can prevent microbial growth and related
harmful skin infections
__________________
Three hits in pubmed for ( amps + psoriasis )
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20psoria*+amps
The first one of those three,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16457755
[Innate antimicrobial peptides in the skin]
[Article in French]
Schroder JM, Harder J.
Clinical research unit, Department of Dermatology, University Hospital
Schleswig-Holstein, Campus Kiel, Schittenhelmstrasse 7, D-24105 Kiel,
Allemagne. jschr...@dermatology.uni-kiel.de
Human skin is always in contact with the environment and is covered
with a characteristic microflora, but it is usually not infected.
Although desquamation and secretion of mucus lead to a permanent
renewal of these body surfaces and simultaneous elimination of
microorganisms adhering to these layers, another reason for this
natural resistance might be the existence of a "chemical barrier"
consisting in constitutively and inducibly produced antimicrobial
peptides and proteins (AMPs), which include some ss-defensins, RNase 7,
the S100-protein psoriasin and the cathelicidin LL-37. Most of these
AMPs can be induced in vitro in epithelial cells by proinflammatory
cytokines or bacteria. In vivo, AMPs are mainly expressed in uppermost
and differentiated parts of inflammatory lesions and wounds, but some
are also focally expressed in skin in the absence of inflammation,
suggesting that apart from inflammatory mediators, also
non-inflammatory stimuli of endogenous and/or exogenous origin can
stimulate AMP-synthesis. Increased levels of ____AMPs____ in psoriatic
lesions may explain why psoriasis patients rarely suffer from skin
infections. Further, an increased infection rate in atopic dermatitis
patients could be the consequence of decreased levels of AMPs in atopic
lesions. These observations may indicate an important role of the
"chemical skin barrier" in prevention of skin infection and suggest
that artificial stimulation of this system, without inflammation, would
be beneficial as "immune stimulus".
PMID: 16457755
----------------------------------
But, what if amps are increased in severe psoriasis but nearly normal
in low pasi
cases? That could explain the Th1/Th2 mix uP's we have in this group
between
psoriatics and offer explantions for the YMMV dilemma's we encounter so
often.
randall... slow day, get the boron
JXStern
>Many biotech companies search for useful products one at a time. VLST's
>approach is based on an observation that company principals Craig Smith
>and Ray Goodwin made while at Immunex, where they worked on the
>blockbuster arthritis drug Enbrel: Viruses have genes that suppress the
>immune system. Those genes aren't useful as drugs themselves. But they
>can be used to find analogous genes in humans that would have a similar
>immune-suppressing ability, Gillis said.
Maybe, but wouldn't they suppress the Th2 cells?
J.
randall
Ok, we know the DCs talk to the T's
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16777399
And in this case a virus (we're not just looking at it's dna to
dertermine a pathway, but
the virus) is affecting a strong Th1 skew (just like in P) to a mixed
bag
of Th1/Th2.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10449525
So, the search would be for stats and virus,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20viru*+stat
Yet, their only looking at these pathways to see what the viri are
doing to T helper cells. So as to learn how to manipulate the pathway
without the virus, and use maybe a folded protein or the dna as a
template to configure their new targets
These would be beyond the biologicals or at least a step or two
upstream.
Say, the actual culprit is a mixture of things working off p genes and
a virus,
chances are we can't stop either, but most likely can indirectly
influence both.
IMHO that would still be raising IL-10 a notch or two to lower TH1's a
notch or three.
And i would aim all my efforts to the gut/mucosal area to create the
biota
that would do just that for people with Ai conditions.
>
> Maybe, but wouldn't they suppress the Th2 cells?
Just as long as they stimulate the $grant$ pathways they can
correct for the side effects downstream. lol
Certainly, their looking for a pathway that will incorporate what is
and isn't known in the quest to fix Ai (autoimmune) pathogenesis.
Lets check for the glyco pathways as they unfold.
http://glycob.oxfordjournals.org/cgi/content/abstract/16/7/103R?etoc
And immune,
http://www.signaling-gateway.org/molecule/query?afcsid=A003881
Ckip1 (aka- TNF intracellular domain-interacting protein)
http://www.signaling-gateway.org/molecule/query?afcsid=A003474
And why I posted this ovalbumin (ova) story yesterday,
http://www.signaling-gateway.org/update/updates/200606/nri1862.html
Yet it keeps getting to technical to follow,
http://www.nature.com/ni/journal/v4/n4/abs/ni913.html
With sugar-fats, folded proteins and the rest of the above, we're
up to beyond advanced organic chemistry for dummies.
Yet if i continue to take chondroitin sulfate maybe it's doing
something in
my gut with other things already there or newly consumed (IP6 ?),
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16779785
Metabolism and biochemical/physiological roles of chondroitin sulfates:
analysis of endogenous and supplemental chondroitin sulfates in blood
circulation.
Lamari FN, Theocharis AD, Asimakopoulou AP, Malavaki CJ, Karamanos NK.
Department of Pharmacy, Laboratory of Pharmacognosy and Chemistry of
Natural Products, University of Patras, 26500 Patras, Greece.
Chondroitin sulfate (CS) is a linear heteropolysaccharide consisting of
repeating disaccharide units of glucuronic acid and galactosamine,
which is commonly sulfated at C-4 and/or C-6 of galactosamine. The
administration of CS as a supplement or a drug for the treatment of
osteoarthrosis, the prevention of subsequent coronary events, treatment
of psoriasis and ophthalmic diseases has been suggested. Much debate on
the metabolism of CS and therefore the effectiveness of these
treatments, especially after oral administration, has arisen due to the
macromolecular nature of CS. Difficulties in analysing CS in blood due
to the low endogenous concentrations and the covalent and anionic
complexes with proteins have hampered the resolution of these issues.
In this review, the information on the pharmacokinetics of CS obtained
from studies in experimental animals and in humans is presented.
Emphasis has been given to the analytical methods used for the
determination of glycosaminoglycans, intact CS and CS-derived
disaccharides in blood serum and plasma. Copyright (c) 2006 John Wiley
& Sons, Ltd.
PMID: 16779785
What the heck is a heteropolysaccharide? The oPPosite of a homo-... lol
Ok i'll find it,
http://en.wikipedia.org/wiki/Heterosaccharide
Thats close enough.
But if your not sure, then do the web search, (and add in P as the
kicker)
http://www.google.com/search?hl=en&lr=&q=heteropolysaccharide+psoriasis&btnG=Search
And what about a group search of chondroitin for what we've speculated
in the p ng,
http://groups.google.com/groups/search?q=chondroitin+sulfate+psoriasis&qt_s=Search
I'll try to tie some of these results to-gether. You do see that the Ai
disease pathways
overlaP? Or do they?
And speaking of proteins, folded or not, this one keeps rearing its
head,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16778811
S100A7 (Psoriasin): a Story of Mice and Men.
Eckert RL, Lee KC.
[1] 1Department of Physiology and Biophysics, Case Western Reserve
University School of Medicine, Cleveland, Ohio, USA; [2] 2Department of
Biochemistry, Case Western Reserve University School of Medicine,
Cleveland, Ohio, USA; [3] 3Department of Dermatology, Case Western
Reserve University School of Medicine, Cleveland, Ohio, USA; [4]
4Department of Oncology, Case Western Reserve University School of
Medicine, Cleveland, Ohio, USA.
S100 proteins are calcium-regulated proteins that regulate fundamental
biological processes. S100A7 (psoriasin), functions as a
transglutaminase substrate/cornified envelope precursor, signal
transduction protein, chemokine, and antibacterial protein in normal
epidermis. S100A7 is markedly increased in epidermal hyperproliferative
disorders. The murine homolog of S100A7 and S10015 has been identified,
providing a valuable tool for studying the regulation and function of
this protein in epidermis.Journal of Investigative Dermatology (2006)
126, 1442-1444. doi:10.1038/sj.jid.5700265.
PMID: 16778811
And if not the proteins then these sugar-fats are PoPing uP with
cytokines involved in
P Pathways, (so nice to have mice as a test bed again)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16778121
IL-20 Is Expressed in Atherosclerosis Plaques and Promotes
Atherosclerosis in Apolipoprotein E-Deficient Mice.
Chen WY, Cheng BC, Jiang MJ, Hsieh MY, Chang MS.
Institute of Basic Medical Sciences, Department of Biochemistry and
Molecular Biology, Department of Cell Biology and Anatomy, College of
Medicine, National Cheng Kung University, and Chi-Mei Medical Center,
Tainan, Taiwan.
OBJECTIVE: Atherosclerosis is a chronic inflammatory disease with
immune cell infiltration. Various cytokines and chemokines have been
characterized as pro- or antiatherogenic factors. IL-20 (IL-20) belongs
to the IL-10 family and is a proinflammatory cytokine involved in the
pathogenesis of psoriasis. However, the association between IL-20 and
atherosclerosis is undetermined. Therefore, we sought to investigate
whether IL-20 is associated with atherosclerosis. METHODS AND RESULTS:
We examined the expression of IL-20 and its receptor complex
IL-20R1/IL-20R2 in atherosclerotic lesions of humans and mice using
immunohistochemical staining. IL-20 was expressed in macrophage-rich
areas. Both IL-20 and IL-20R1/IL-20R2 were expressed by endothelial
cells lining the intimal microvessels, vasa vasorum, but rarely in
nonatherosclerotic arteries. We used reverse-transcription polymerase
chain reaction to analyze gene expression. IL-20 transcripts increased
in hypoxic monocytes and monocytes treated with oxidized low-density
lipoprotein. The expression of IL-20R1 and IL-20R2 was also upregulated
by HUVECs in response to hypoxic treatment. Incubating IL-20 with
HUVECs upregulated CXCL9 and CXCL11 transcripts. Furthermore, in vivo
administration of IL-20 expression vector using intramuscular
electroporation promoted atherosclerosis in apolipoprotein E-deficient
mice. CONCLUSIONS: Our data suggest that IL-20 is a proatherogenic
cytokine that contributes to the progression of atherosclerosis.
PMID: 16778121
For IL-20 & P,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16645593
Here's a good one. Does PsA even exist as a distinct rheumatic disease?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16777575
Psoriatic arthritis: One or more diseases?
Fitzgerald O, Dougados M.
St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Psoriatic arthritis (PsA) is a common, debilitating auto-immune disease
with diverse clinical features. In this paper, published evidence is
examined, which addresses the issues that (a) PsA exists; and (b) PsA
can or cannot be viewed as a distinct rheumatic disease from other
spondyloarthritides. Evidence derived from epidemiological, clinical,
genetic and immunohistological studies is included. Summarizing the
evidence, it is clear that PsA does indeed exist, with the prevalence
of rheumatic disease in patients with psoriasis (Ps) higher than would
be expected. Certain clinical features also occur more commonly in PsA,
although none can differentiate consistently from other arthropathies.
Both genetic and immunohistological studies suggest that PsA, both
oligo- and polyarticular disease, can be clearly separated from
rheumatoid arthritis and that it belongs to the family of
spondyloarthritides. The presence of Ps may confer a more severe
clinical phenotype with poor radiological outcome. It may be that, with
time, a specific genetic marker or diagnostic feature will emerge;
additional, more detailed pathogenic studies are required. In the
meanwhile, particularly with new treatments being evaluated, it is
important to continue to develop specific classification or diagnostic
criteria and to define both clinical and laboratory-based outcome
measures.
PMID: 16777575
If we know the PsA pathway it may give us the clue!
Concepts and epidemiology of spondyloarthritis.
Sieper J, Rudwaleit M, Khan MA, Braun J.
Rheumatology, Charite, Campus Benjamin Franklin, Berlin, Germany.
The term 'spondyloarthritides' (SpA) comprises ankylosing spondylitis
(AS), reactive arthritis, arthritis/spondylitis with inflammatory bowel
disease, and arthritis/spondylitis with psoriasis. The main links
between these diseases are an association with HLA-B27 and a similar
clinical picture. Patients normally present with chronic low back pain
or asymmetrical arthritis, predominantly of the lower limbs, and an
overlap of these symptoms often occurs. AS is regarded as the most
severe subtype. Recent attention has focused on earlier diagnosis of AS
among patients with chronic low back, and this is becoming more
important as effective therapies for early treatment have become
available. AS is a disease of young people, normally starting in the
third decade of life. The incidence and prevalence rates of AS, and of
SpA as a whole, are strongly dependent and are directly correlated to
the prevalence of HLA-B27 in a given population. Incidence rates of
0.5-8.2/100 000 population and prevalence rates of 0.2-1.2% have been
described for AS, and about double these figures have been reported for
SpA.
PMID: 16777573
And where did robo poster go? Now with allergy and Ai in the news with
the "hygiene
hypothesis" again, he's out to lunch?
http://www.eurekalert.org/pub_releases/2006-06/dumc-wvl061406.php
Wild vs. lab rodent comparison supports hygiene hypothesis
[...]
Up to 50 million Americans are estimated to suffer from allergies, and
another 8 million have some form of autoimmune disorder, which occurs
when an overactive immune system attacks tissues in the body. Examples
of autoimmune disorders include lupus, insulin-dependant diabetes,
rheumatoid arthritis and scleroderma.
"The most commonly accepted explanation for this high incidence of
allergy and perhaps autoimmune disease is the hygiene hypothesis,"
Parker said. But this hypothesis has not been thoroughly tested in
animal studies, he said, and the few studies conducted have focused on
specific pathogens or parasites.
The Duke researchers decided to study the hypothesis by comparing the
immune systems of wild house mice and common rats to laboratory mice
and rats. The strength of this model, Parker said, is that it takes
into account the totality of the animals living in their natural
environment.
Specifically, the team focused the animals' production of various
antibodies, known as immunoglobulins, either associated with autoimmune
disease or associated with allergy. When an animal encounters a foreign
invader, or antigen, its immune system kicks into action by producing
antibodies that bind to the invader and destroy it.
Of the many classes of immunoglobulins (Ig), the IgG type is often
involved in autoimmune disease, while the IgE type is likely a key
defender against parasites and has been implicated in allergic
reactions in humans, Parker said.
For their experiments, the researchers trapped wild rats in rural and
urban settings in North Carolina and trapped wild mice in Wisconsin.
They then measured the levels of antibodies in the blood of the wild
rodents and compared the levels to those observed in mice and rats
housed in Duke animal facilities.
All of the wild rodents had higher levels of IgG and IgE, with the IgE
showing the most pronounced difference, Parker said. Additionally, the
wild rodents had higher levels of a particular type of IgG called
polyreactive, autoreactive IgG, which is associated with autoimmune
disease in hygienic humans and rodents. However, the increased levels
of these antibodies did not presumably cause untoward reactions in the
wild rodents, Parker said.
That wild rodents had higher levels of IgE was not unexpected, he
added, since wild rodents would likely have encountered parasites that
activated the production of antibodies as protection. However, the
production of polyreactive, autoreactive IgG by the wild rodents was
unexpected: Polyreactive, autoreactive antibodies are always found to
be a type of IgM, a different type of antibody than IgG, although all
previous studies have focused on hygienic populations.
"These results appear to demonstrate that the environment has profound
effects on the production of IgE and autoreactive IgG," Parker said.
"While the production of these two antibody types lead to autoimmune
disease and allergy, respectively, in the laboratory animals, their
production seemed to represent a nonpathogenic, protective response to
the environment by the wild rodents.
"We would expect that the targets of the autoreactive IgG and IgE in
the 'hygienic' laboratory rodents would be substantially different from
the targets of the same antibodies in the wild animals," he said.
In the wild animals, the autoreactive IgG likely bind to environmental
antigens and therefore do not have deleterious effects, Parker said.
"However, autoreactive IgG in hygienic animals can bind avidly to the
body's own cells, which can lead to autoimmune disease," he said. "In a
parallel fashion, the IgE in the wild animals is protective because the
antibodies bind to parasite antigens, while the same antibodies in
laboratory animals would bind to abundant but harmless environmental
antigens, leading to allergies to those antigens."
"These results are consistent with the idea that animals without access
to modern medicine have high levels of autoimmune-like and
allergic-like immune responses that represent appropriate responses to
unknown factors in their environment," he said.
Although this study suggests that the environment plays an important
role in how the immune systems in animals develop, genetics is likely
to be involved as well, Parker said. He now is planning additional
studies to help decipher the full role of genetics.
Also, his group is planning further studies of the hygiene hypothesis,
using the new rodent model to examine other factors that may be
contributing to the higher rates of allergy and autoimmune diseases of
humans in industrialized societies, such as lack of exercise, increased
mental stress and the consumption of processed food. <sniP>
---------------------------------------------------------------------------------
OK. I got it.
Instead of running a DNA array anaylsis in vitro. You put the dirt in
to
the humans and run it in vivo so as to induce the immune system
to create pathways protective of outside pathogens. And pray
you don't get really bad dirt. lol
May not correct for P genes, but at least we'll understand, the precise
pathways enough to correct other tangential inflammatory
genes/pathways.
randall... i don't know.. but I hope someone figures it out!
randall
Will Google CLEAR uP their P ads or let the frauds hide behind the
free speech arena?
( for free speech:: http://en.wikipedia.org/wiki/Free_speech )
How many times when googling around do you look at the sponsored ads
on the right hand column?
http://releases.usnewswire.com/GetRelease.asp?id=67784
Google Asked by Psoriasis Group to Stop Permitting Paid Ads to Tout
Phony Medical 'Cures'
6/20/2006 7:30:00 AM
To: National Desk, Health Reporter
Contact: Michael Paranzino of Psoriasis Cure Now, 202-253-4863 or
michael @psorcurenow.org Web: http://www.psorcurenow.org
KENSINGTON, Md., June 20 /U.S. Newswire/ -- "Psoriasis Cure Now," a
nonprofit patient advocacy group, today asked internet search giant
Google to enforce its own corporate policy against accepting
advertisements that promote phony cures for incurable diseases. Google
is currently running numerous paid ads designed to deceive people with
psoriasis, a painful, incurable and often debilitating immune system
disease that affects as many as 7.5 million Americans.
"The Google brand stands for integrity and credibility," said Michael
Paranzino, president of Psoriasis Cure Now, "which is why we have asked
Google to enforce its own sensible policy prohibiting ads for phony
medical 'cures.' People with painful, incurable diseases are
particularly vulnerable to scam artists seeking to prey on their
misfortune. We hope Google will enforce its policy to protect its users
from false and potentially unhealthy advertising."
Google's content policy clearly states: "Advertising is not permitted
for the promotion of miracle cures, such as 'Cure cancer overnight!'"
( https://adwords.google.com/select/contentpolicy.html ) Yet as of
yesterday, nine different paid ads alongside search results for the
word "psoriasis" made just that kind of bogus claim, including:
"Psoriasis Can Be Cured"; "New Psoriasis Cure"; "eradicate your
psoriasis in 2-3 days"; and "treatment guaranteed to end Psoriasis."
Unfortunately, there is no cure for psoriasis. In fact, scientists
believe a dozen or more different genes may play a role in this complex
disease, along with environmental triggers that make psoriasis even
more difficult to treat.
Google competitor Yahoo! is not running any psoriasis advertisements
that make obviously false claims. "We applaud Yahoo! for its practice
and look forward to Google enforcing its policy to protect both its
users and its corporate image," Paranzino added.
For more on psoriasis and psoriatic arthritis, visit the Psoriasis Cure
Now website: http://www.psorcurenow.org
-----------------------
Lets do the P search and see,
http://www.google.com/search?hl=en&lr=&q=psoriasis&btnG=Search
Can't fault the herbal ads.
Unless you've done the kalawalla or merry clinic herbs their ok ad
wise.
An old CUREster is still be to be found with his on going:::
"Psoriasis Can Be Cured
Doctor reveals self-help treatment
guaranteed to end psoriasis!
www.psoriasiscured.com"
Maybe he's selling herbs from the two hits above? LOL
For a take on this one,
http://groups.google.com/groups?hl=en&lr=&q=psoriasiscured.com&btnG=Search&sa=N&tab=wg
You spend $30 and he tells you what herbs to eat.
Or you could use the one's right here mentioned in the P group.
But then you'd have to clear up your diet to get more bang for
your herb. And then get some sunshine. And then....and.... an... a
----------------------------------------------------------------------
Abstract time,
PPAR-gamma Gene Polymorphisms and Psoriatic Arthritis.
Butt C, Gladman D, Rahman P.
OBJECTIVE: Peroxisome proliferator-activated receptor-gamma
(PPAR-gamma) activation has been shown to play a role in suppressing
angiogenesis and inflammation, both important pathological features of
psoriatic arthritis (PsA). Given the potential physiological role for
PPAR-gamma in PsA, we examined known coding polymorphisms in the
PPAR-gamma gene in a Caucasian population. METHODS: PsA was diagnosed
as an inflammatory arthritis in patients with psoriasis, in the absence
of other etiologies for inflammatory arthritis. Control subjects were
ascertained from the same population and were all Caucasian. DNA
samples were genotyped for 4 PPAR-gamma variants by time-of-flight mass
spectrometry using the Sequenom platform. All 4 single-nucleotide
polymorphisms (SNP) were previously-reported coding variations, 3 of
which caused an amino acid change: Pro12Ala (rs1801282), Pro40Ala
(rs1805192), and Pro115Gln (rs1800571); the fourth SNP, C161T
(rs3856806), was synonymous. All primers were designed using Sequenom
SpectroDesigner software, and scanned using a mass spectrometry
workstation. RESULTS: Of the 4 SNP examined, Pro40Ala and Pro115Gln
were found to be nonpolymorphic in our population. Minor allele
frequency for patients with PsA and controls for Pro12Ala (G) were 9.0%
vs 13.8% (p = 0.017) and for C161T (T) 10.7% vs 12.0% (p = 0.56),
respectively. All genotypes satisfied Hardy-Weinberg equilibrium.
CONCLUSION: An association between PsA and a known coding SNP of the
PPAR-gamma gene was observed in our Caucasian population. Further
studies are now warranted for validation of our findings in an
independent cohort.
PMID: 16783862
--------------------------------
TNF comes from fat cells (adipose).
http://en.wikipedia.org/wiki/Adipose_tissue
So, it's not uncommon to find P and fat involved
in the PPAR part of many psor pathways. Worth looking at,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16781085
Chronic inflammation in psoriasis and obesity: Implications for
therapy.
Hamminga EA, van der Lely AJ, Neumann HA, Thio HB.
Department of Dermatology and Venereology, Erasmus Medical Center, Dr.
Molenwaterplein 40, 3015 GD Rotterdam, The Netherlands.
A recent study has shown an indisputable relationship between psoriasis
and obesity. Obesity leads to a higher risk in developing psoriasis and
a poorer long-term clinical outcome of psoriasis. Furthermore, loosing
weight may improve the psoriasis. A network of pro-inflammatory
cytokines (especially tumour necrosis factor alpha (TNF-alpha)) is
believed to play an important role in the pathophysiology of both
obesity and psoriasis. The chronic low-level inflammation- as seen in
obesity - may contribute to the extent of psoriatic lesions in obese
patients. TNF-alpha in obesity is presumed to be derived from
inflammatory cells (macrophages) in the adipose tissue and in psoriasis
from activated T cells. Several drugs, such as peroxisome proliferator
activated receptor (PPAR)-gamma agonists and TNF-alpha blocking agents,
that target the pro-inflammatory pathways involved in both psoriasis
and obesity have proven their benefit in the treatment of these
entities. Furthermore, changes in levels of metabolic hormones as
ghrelin and leptin in obesity may also play a role in the pathogenesis
of deterioration of psoriasis by their potency to release
pro-inflammatory mediators (e.g. interleukin (IL) 6 and TNF-alpha). We
hypothesize that the treatment of obese psoriasis patient could be
focused on reducing the obesity-induced inflammation. Reducing this
obesity-induced inflammation may finally lead to a better clinical
outcome. Weight loss could lead to a less inflammatory state by
reducing concentrations of TNF-alpha, IL-6, leptin and improving
insulin sensitivity.
PMID: 16781085
---------------------------------------------
If PPAR + P Genes are worth looking at. How about your mind? Or your
mind
looking at you?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16781625
Psychosomatic plasticity: an "emergent property" of personality
research?
Jawer M.
Psychosomatic plasticity, defined as an extreme capacity to turn
suggestions into bodily realities, is as phenomenon well worth
investigating because it challenges mainstream conceptions about the
relationship between mind and body in health as well as illness. The
field of psychoneuroimmunology (PNI) offers a framework within which to
understand this phenomenon because PNI makes a compelling case for the
biological unity of self. Hartmann's Boundaries concept is particularly
applicable because it suggests that the minds of "thin-boundary"
persons are relatively fluid and able to make numerous connections.
Wilson and Barber's identification of the fantasy prone person and
Thalbourne's transliminality concept are similarly relevant. Taking
these explorations a step further, this author proposes that the flow
of feeling within individuals represents the key to psychosomatic
plasticity. Blushing, psoriasis, and immune reactions are offered as
examples, as are more anomalous reports such as those provided by heart
transplantation recipients and cases said to be indicative of
reincarnation. In each instance, persons who are highly sensitive (ie,
have a speedier and more direct flow of feeling) are more likely to
evidence physical reactions. Psychosomatic plasticity represents an
emerging area of interest in personality research, one that clearly
merits further investigation.
PMID: 16781625
-------------------------------------------------
randall...eating only herbs will stoP the ppar-ish P fate..
randall
P News, east and west coast today.
http://releases.usnewswire.com/GetRelease.asp?id=67993
Psoriasis Cure Now Cheers U.S. House of Representatives for Supporting
Psoriasis Research in Key Appropriations Bill
6/22/2006 7:30:00 AM
To: National Desk
Contact: Michael Paranzino of Psoriasis Cure Now, 202-253-4863, michael
@psorcurenow.org
KENSINGTON, Md., June 22 /U.S. Newswire/ -- "Psoriasis Cure Now," a
nonprofit patient advocacy group, today praised the House
Appropriations Committee for its strong language in support of
expanding federally funded psoriasis research. The language is
contained in the Report accompanying the Fiscal Year 2007 Labor- HHS
Appropriations bill, H.R. 5647, which was filed on Tuesday.
"We applaud the House Appropriations Committee for standing with the
millions of Americans who face psoriasis and psoriatic arthritis every
day," said Michael Paranzino, president of Psoriasis Cure Now. "Even as
this Committee has doubled biomedical research funding at the National
Institutes of Health over the last decade, psoriasis research funding
has dropped by 22 percent. This strong message coming from the House
will, we hope, get the attention of NIH and lead to a healthier future
for the as many as 7.5 million Americans with this incurable disease.
While many lawmakers helped make this happen, we particularly wish to
thank Chairman Ralph Regula of Ohio, Rep. Rosa DeLauro of Connecticut,
Reps. Tim Murphy and Jim Gerlach of Pennsylvania, and Rep. Stephen
Lynch of Massachusetts for their leadership on this important issue."
The National Psoriasis Foundation and Psoriasis Cure Now have been
working together this year to mobilize Congressional support for
psoriasis research and this Report language.
"The National Psoriasis Foundation and its impressive grass roots
support have been powerful partners in this effort, and we look forward
to continuing to work with them as we seek similar language from the
United States Senate," Paranzino added.
The House Report includes language urging the NIH Director to
coordinate and expand psoriasis research at various Institutes;
encouraging the National Institutes of Mental Health to investigate the
mental health aspects of psoriasis; calling on the National Institute
of Arthritis and Musculoskeletal and Skin Diseases to expand its
research portfolio on skin disease; and urging the Centers for Disease
Control and Prevention to collect psoriasis incidence and prevalence
data, including for children, who have not always been counted in past
studies. Hundreds of thousands of children and teens are estimated to
have psoriasis. The House Report language on psoriasis is reprinted
here: http://www.psorcurenow.org/house07.php .
The full House has not yet voted on the Labor-HHS Appropriations Bill,
nor has the Senate passed its version. Psoriasis Cure Now is continuing
to generate constituent letters in support of this important language.
Everyone who believes in psoriasis research is invited to write their
lawmakers through the Psoriasis Cure Now website at this address:
http://www.psorcurenow.org
-------------------------------------------------------
Got a metaPhor for P?
What one author from the Los Angleles city beat compares P to.
http://www.lacitybeat.com/article.php?id=3933&IssueNum=159
The Tao of the Barbecue Cycle
As humans, we crave meaning. Not to
In the winter, folks gather around a fireplace because it provides
warmth and represents survival. On an atavistic level, the flickering
of the flame is a window to the soul and to the history of the species.
Fire speaks to us on a primeval level. The flame is mesmerizing, and
the excitation and expansion of atoms release heat and light, summoning
notions of the big bang itself, something that Homo Erectus must've
grokked intuitively, all the way down to his hideous, unkempt toenails.
Fire is a totem for all seasons: In the summer, the clans gather around
outdoor barbecues and summon a flame that symbolizes survival in the
form of sustenance. Following a ritual started by Early Man - who
rubbed two sticks together, generating friction, and then ran a stick
through the guts of a warthog and called it supper - tribes cook
their protein, which makes meat easier to digest and prevents disease.
[...]
The BBQ cycle goes like this: The lighting of charcoal releases carbon
gases that warm the earth's atmosphere, slowly tearing a hole in the
fabric that protects the planet from ultraviolet radiation. As the
coals die down and glow like Satan's _____psoriasis____, meat - say
a rack of raspberry-soaked beef ribs - is placed on the grill's hot
surface. <sniP>
----------------------------------------------------------------
Ok. So we do need to make our minds more plastic.
What was that abstract from a few days back about
Psychosomatic plasticity and personality about?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16781625
We, like do it in our minds or something?
Maybe we should think about time in reverse?
http://www.signonsandiego.com/uniontrib/20060622/news_lz1c22cause.html
CAUSE AND DEFECT
[...]
human consciousness and intent (instructions to think positive) induced
the numbers to assume a specific condition or quantum state.
The physics of consciousness is controversial, to say the least. And
Stapp is first to say much more study and experimentation is necessary,
especially by respected scientists in well-regarded scientific
journals.
"You'd think people would want to either refute or confirm some of
these reports," said Stapp, "but the only people willing to test
them are people who already tend to believe them. Most mainstream labs
shy away for fear of sullying their reputations, as if they would be
dirtying their hands by even imagining some of this is possible."
Mind games
For Stapp, who now works at the Lawrence Livermore National
Laboratories, it's not inconceivable that quantum mechanics plays some
role in alleged paranormal phenomena like extrasensory perception (ESP)
and remote viewing, which is the projection of one's consciousness to
distant locations.
These abilities may be a consequence of nonlocality, a well-established
quantum concept that says entities far-flung in distance or time are
still entangled and interact via a faster-than-light, quantum
mechanical connection.
Einstein called this phenomenon "spooky action at a distance." He
couldn't explain it, didn't like it and regarded it as quantum
trickery.
In recent decades, nonlocality has been repeatedly observed, tested and
measured in experiments. In one seminal experiment in 1982, physicist
Alan Aspect at the University of Paris noted that by changing the
polarity of one speeding photon (a particle of light) he could induce
another photon from the same source speeding in the opposite direction
to change its polarity. The interaction happened faster than light,
with sufficient distance between the photons that they shouldn't have
"known" what was happening to the other. And yet, inexplicably,
there was some sort of link.
In contrast, paranormal phenomena like ESP and remote viewing are not
as well-substantiated. Supporting evidence tends to be anecdotal.
Purposeful deception and fraud are common.
In the 1970s, the U.S. Army and the CIA spent millions investigating
the potential of remote viewing, but that effort apparently went for
naught and funding ceased. In 1979, the Princeton Engineering Anomalies
Research (PEAR) program began investigating interaction between human
consciousness and the physical world. Over the years, PEAR has produced
a wealth of data indicating human intent by itself, without any
physical connection, can alter the behavior or results of unthinking
machines. The PEAR experiments, many similar to Schmidt's 1992 random
number generator test, produced only small effects, but they were
observable, measurable and repeatable.
PEAR's operations, however, are now in the process of closing down,
with researchers moving on to other institutions.
Dobyns, an analytical coordinator for PEAR, said he still thinks
"parapsychology and related areas are useful places to look for
evidence (of reverse causation)."
But he is not optimistic that many mainstream physicists will ever take
up the cause. "They say it's impossible because there's no evidence
and there's no evidence because it's impossible."
But physicists like Sheehan say what we do understand about the
universe fundamentally depends upon the idea that time is fluid and
dynamic. "To say that it's impossible for the future to influence the
past is to deny half of the predictions of the laws of physics," he
said.
Nobody's predicting a speedy or conclusive resolution to the question
of reverse causation. Sheehan says it's the journey that counts, how we
get from Point A to B to C - or, perhaps, from C to B to A.
____________________________________________
How about from C to P or C of P? If we pretend its the future and p is
cured, then what you see is only the future waiting to haPPen. :)
Huh?
Maybe p makes us live in the here and now boys?
--------------------------------------------------------
At least P doesn't kill you. But sometimes it feels that way.
Try this next gene defect on for cause.
You suspect you have Af?
http://biz.yahoo.com/prnews/060622/mo040.html?.v=5
[...]
gene (GJA5) which makes a protein known as Connexin 40. The protein is
specific to the atrial tissue of the heart and plays a crucial role in
how electrical impulses are conducted. They discovered genetic
mutations in the Connexin 40 gene in AF patients. Researchers proved
the disease was tissue-specific and not present in all body cells by
detecting the mutation only in the heart tissue and not in the blood
cells of affected patients. <sniP>
------------------------------------
randall... pretending the future is now, cause i have a defect of
plasticity i think?
randall
P News from around the world.
Yesterday was east and west of the US.
Today is more exotic. We have the babu cure for aids/hiv
spamming the group with ND-ish nostrums. He says that
the body is filled with morbid matter and his naturopathic
treatment will augment 2G12 sugars to reverse the hiv/aids virus.
OK...
Timely, that these next ones showed up today for P News.
Tibet and Peru. To rather high places. The twin roofs of the world
should have some exotic herbs.
Ayurvedic medicine and Tibetan herbs for clothes.
http://www.thehindubusinessline.com/life/2006/06/23/stories/2006062300070200.htm
[...]
Last year, the State Coir Department conducted a six-month clinical
trial at Ayurveda College, Thiruvananthapuram. Four rooms were set
aside for treating rheumatism, allergy, hypertension, diabetes,
psoriasis and other skin ailments. The clothes, bed linen and
mattresses for patients were dyed in herbs and the walls, ceiling and
floor lined with medicated coir.
"We treated around 40 people. And the response was remarkably good,
especially in cases of arthritis and skin ailments," says Dr
Vishwanathan, former head of the Drug Research Department of the
college.
[...]
`Chandan' and `khus khus' saris with thin `zari' border are moving
really well. "It feels great to wear the essence of herbs. It breathes
in positive vibes," says Jayashree, a bank employee.
Herbal reams from Thumpodu are reaching foreign shores as well,
although the society is not into direct exports. "There is a lot of
demand from Italy, Germany, France, the US and Gulf. They mainly buy
dress material, bed linen and furnishing," says Rajan. The society
members feel that the khus khus purdahs will be a big hit in Saudi
Arabia. Decking up houseboat interiors with medicated coir is next on
their agenda.
"So much effort has gone into making ayur vastra that we want to
preserve our rights," says Dr Ravi, who was advisor to the Government
in charge of sustainable development and offered all help for this
experiment.
A scientific validation study is under way at the Regional Research
Laboratory in Thiruvananthapuram.
Once it is over, the society's patent dreams may just go green.
<end>
How about shirts and pants made with chile pePPer dyes?
We could call it light my fire. lol
-------------------------------------------------
I wonder what khus khus are?
http://indianfood.about.com/od/glossaryofterms/g/khus.htm
H'mm ground uP poPPy seeds!
It can't be the elusive blue poppy, Bhutan's national flower,
http://www.mtsobek.com/features/Himalaya/images/04_aboutHimalaya/p9.jpg
http://www.neoncarrot.co.uk/h_journal/india_diary/tl04_07_leaving_drinks.
html
[...]
Siddhu is Manali's answer to the Tibetan momo and our favourite local
speciality. Siddhus are hand sized steamed pasta thingies, stuffed with
a viciously green paste made of poppy seeds, fresh coriander, nuts,
garlic, onion and spices. Local wisdom has it that they are winter
food, not suitable for consumption in summer since the ingredients are
so energy-ridden and also because they're fairly work intensive to
make. As we'll be leaving for Europe soon it's not all that difficult
to persuade Rabet and his family to make an exception, and after Woody
and I come back from a day in Kullu we stuff ourselves with their
excellent Siddhu - good stomach lining for the copious consumption of
whisky that follows. <sniP>
Yet, one wonders if using the seeds for paste is simply whats left over
after
the main reasons for growing them,
http://cemoti.revues.org/document687.html
Not that i'm worried about any narco effects for these food items,
http://www.faeriesfinest.com/D216.html
The dried seed of the opium poppy is used as food, flavoring, and is
the source of poppy-seed oil. Although the botanical name for the poppy
flower means "sleep bearing", poppy seeds have no narcotic properties
because the fluid that is made into opium is only present in the buds
before the seeds are fully formed.
Poppy seed is an ancient spice. Written records mention its use as a
condiment as early as the first century A.D. and seed capsules have
been found in the remains of prehistoric lake dwellings in Switzerland.
The seeds are small, grayish blue to dark blue in color with a faint
nutlike aroma and a mild, nutty taste especially popular in breads and
other baked goods. Next time you make potato salad, try adding some
poppy seed to the dressing. <end>
If you are interested in the stronger alkaloid forms,
http://www.uni-graz.at/~katzer/engl/Papa_som.html
Hello trouble,
http://www.uni-graz.at/~katzer/pictures/papa_11.jpg
If you think your full of morbid matter this is one
alkaloid that may make that a self fulfilling realization of the
worse kind. Another negative lifestyle from a female herb?
((((((((((((((((((((((((((((((((((((()))))))))))))))))))))))))))))))))))))))
Lets stay out of that in Peru.
http://www.guardian.co.uk/science/story/0,,1804037,00.html
Extract from Peruvian plant could speed up wound healing
Alok Jha, science correspondent
Friday June 23, 2006
The Guardian
A traditional medicine from Peru can radically speed up the healing of
wounds. In tests, injuries treated by an extract of the plant Anredera
diffusa healed more than 40% faster than normal.
Scientists said the plant's active ingredient, oleanolic acid, could
speed up the healing of cuts and abrasions as well as easing the pain
of ulcer sufferers. "Impaired wound healing may cause severe
health-related complications, such as infections and tissue necrosis,"
write the researchers in the Journal of Natural Products, published
today. "These ailments have spurred the search for wound-healing agents
from ethnomedicinal sources."
Gerald Hammond, a chemist at the University of Louisville, Kentucky,
who led the research, said that his work was based on botanical
observations on A diffusa, known locally as lloto, that had been made
by Peruvians for centuries. Locals normally use wet lloto leaves as a
dressing for wounds. Professor Hammond's team extracted the oleanolic
acid, a chemical already available in skin care products.
His team applied oleanolic acid to a group of mice with wounds and
measured how quickly they healed. "You measure how much weight it takes
to reopen the wound - the more weight it takes compared to the control,
the better," said Prof Hammond. His team found that the mice treated
with oleanolic acid healed 43% faster than the untreated mice. The best
results were obtained by applying 40 micrograms of oleanolic acid per
gram of a mouse's body weight.
How oleanolic acid does its job is a mystery. "That's a very difficult
question. Wound healing occurs in several stages and each stage is not
well understood," said Prof Hammond.
Even so, he said that there was an important market for drugs that
could speed recovery from wounds. "People don't pay too much attention
to wound healing because most of us have no problem with it," he said.
"But there's a number of people that have problems." He cited the
example of diabetics, many of whom have problems with wounds because of
poor circulation, and people who suffer from bed sores. "It's not
cancer, HIV or heart attack, but there is a market for it."
Though Prof Hammond's team only looked at external wounds, oleanolic
acid had been used, in previous experiments, to treat a wide range of
conditions such as psoriasis and gastric ulcers. For surface wounds, he
said the chemical could easily be developed into an ointment.
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
Hammond only now has gotten back to this herb?
He started looking at it back in 1997 according to the next abstract.
>From 1997
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9080340
Evaluation of the wound-healing activity of selected traditional
medicinal plants from Peru.
Villegas LF, Fernandez ID, Maldonado H, Torres R, Zavaleta A, Vaisberg
AJ, Hammond GB.
Departamento de Ciencias Fisiologicas, Universidad Peruana Cayetano
Heredia, Lima, Peru.
Folk medicine practitioners in Peru employ plant preparations as
wound-healing agents on superficial and internal wounds (gastric
ulcers). The results of a scientific evaluation of the wound-healing
activity of nine plants found in the Amazon jungle near Iquitos and in
the Andes mountains is presented. The species studied were: Peperomia
galioides, Mentzelia cordifolia, Mutisia acuminata, Himatanthus
sucuuba, Spondias mombin, Eleutherine bulbosa, Muehlenbeckia
tamnifolia, ____Anredera diffusa_____ and Jatropha curcas. These plants
have also been examined for their toxicological properties, their
effect on blood pressure, smooth muscle and capillary permeability.
Significant wound-healing activity was detected in Peperomia galioides,
Anredera diffusa and Jatropha curcas. Extracts from Peperomia galioides
and Anredera diffusa had no effect on cell proliferation and did not
exhibit mutagenic activity.
PMID: 9080340
http://www.nolana.com/images/1322/1322_01.jpg
Another jpg of the plant, sure doesn't look like the other picture,
http://fm1.fieldmuseum.org/vrrc/?page=view&id=7750&PHPSESSID=9df94f706d8d936626fff842ada0c214
&
http://fm2.fieldmuseum.org/vrrc/max/BASE-anre-diff-534214.jpg
-------------------------------------------------------------------
Understanding the wound healing process should help to further the
quest for curing psoriasis.
Or you could try the babu cure for aids-- diet and lifestyle.
Or for a lot cheaper you can clean up your biota in the Gi tract
with thewholewhey.com implant and diet for the next month
and any and all P causing morbidity in the Gi tract will be nearly
gone in the next 30-90 days.
You'll feel great but miss out on seeing babu in Tibet.
I for one want to eat that poppy paste on some yak steaks...
yummmmmO!
randall...Life's a crap shoot.. we hate it when it becomes toPical..
____________________________________________________
randall
P news from around the world.
Nothing much in google news for P today.
In the pubmed abstracts we have some fun ones.
-------------------------------------------------------
>From symptom to cause? The skin barrier moves slowly forward.
An update of the defensive barrier function of skin.
Lee SH, Jeong SK, Ahn SK.
Department of Dermatology, Yongdong Severance Hospital, Yonsei
University College of Medicine, 146-92 Dogok-dong, Kangnam-gu, Seoul
135- 720, Korea. ydsh...@yumc.yonsei.ac.kr.
Skin, as the outermost organ in the human body, continuously confronts
the external environment and serves as a primary defense system. The
protective functions of skin include UV-protection, anti-oxidant and
antimicrobial functions. In addition to these protections, skin also
acts as a sensory organ and the primary regulator of body temperature.
Within these important functions, the epidermal permeability barrier,
which controls the transcutaneous movement of water and other
electrolytes, is probably the most important. This permeability barrier
resides in the stratum corneum, a resilient layer composed of
corneocytes and stratum corneum intercellular lipids. Since the first
realization of the structural and biochemical diversities involved in
the stratum corneum, a tremendous amount of work has been performed to
elucidate its roles and functions in the skin, and in humans in
general. The perturbation of the epidermal permeability barrier,
previously speculated to be just a symptom involved in skin diseases,
is currently considered to be a primary pathophysiologic factor for
many skin diseases. In addition, much of the evidence provides support
for the idea that various protective functions in the skin are closely
related or even co-regulated. In this review, the recent achievements
of skin researchers focusing on the functions of the epidermal
permeability barrier and their importance in skin disease, such as
atopic dermatitis and psoriasis, are introduced.
PMID: 16807977
Where is the stratum corneum?
http://www.macrochem.com/site/images/charts_graphs/skin-layers.gif
I posted the ceramide-JNK abstract back in February (06) that this
abstract is sPrung from.
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=ceramides
Read the first and third hits in reverse order. ;~)
I don't know or remember if Manfred used serine/lipids to try and
increase his ceramides at the time?
Seems to be a pretty good trial. I wonder if anyone is fooling
around with it?
---------------------------------------------------------------------------------------------
Moving away from the skin to the nervous system now. Not like their not
linked. lol
Does your nervous system in conjunction with T helper cells (Th1/Th2)
determine the Ai (autoimmune) or I.M.I.D. (immune mediated inflammatory
disease)?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16806730
Sympathetic nervous system plays an important role in the relationship
between immune mediated diseases.
Shahabi S, Hassan ZM, Jazani NH, Ebtekar M.
Department of Microbiology, Immunology and Genetics, Faculty of
Medicine, Urmia University of Medical Sciences, Road of Nazloo, Urmia,
Iran.
T helper (Th) lymphocytes have been classified into distinct subsets,
Th1 and Th2 on the basis of the cytokines they produce. According to
the cross-regulatory properties of Th1 and Th2 cells, one would assume
that to be affected by a Th1 type disease increases susceptibility to a
Th1 type disease and inhibits a Th2 type disease and vice versa about
being affected by a Th2 type disease. However, the pattern of related
diseases does not necessarily follow the conventional pattern of
inhibitory effects of Th1 and Th2 immune responses on each other. For
example, Mycobacteria including BCG, that induce Th1 immune responses;
can modulate some Th1 type autoimmune diseases including MS,
experimental autoimmune encephalomyelitis (EAE; an animal model for
Multiple Sclerosis) and insulin-dependent diabetes mellitus (IDDM)
thereby leading to an alleviation of their symptoms. Also BCG
precipitates a syndrome similar to systemic lupus erythematosus (SLE),
a Th2 type disease; in NOD mice. The coexistence of the major
Th2-mediated atopic diseases such as asthma, eczema and allergic
rhinitis with the Th1-mediated autoimmune conditions including; coeliac
disease (CD), IDDM, rheumatoid arthritis (RA) and psoriasis is another
example that is in apparent disagreement with counter-regulatory
effects of Th1/Th2 phenotypes. HYPOTHESIS: SNS can be stimulated by
pro-inflammatory cytokines, production of which is induced by
mycobacteria including BCG. Although these cytokines can inhibit SNS
activity in the site of inflammation and secondary lymphoid organs,
they increase sympathetic tone in other places. Increased sympathetic
tone can induce an anti-inflammatory and Th2 type milieu. This milieu
can inhibit MS and IDDM and provide a susceptible environment for
starting of SLE. Atopic diseases are Th2 type immune mediated diseases;
therefore, they increase the production of Th2 type cytokine and
decrease production of pro-inflammatory cytokines in the site of
allergic reaction and also in secondary lymphoid organs. Therefore,
atopic diseases decrease sympathetic tone in all tissues except in the
sites of allergic reaction and secondary lymphoid organs. Decreased
sympathetic tone results in a pro-inflammatory milieu and in such an
environment, Th1 type autoimmune diseases can affect tissues.
PMID: 16806730
This one says a bug somewhere else turns on the Th1 skew and it
cascades
as the disease according to the genes and their pathways. Or it should
say that. :~)
----------------------------------------------------------------------------------------------
Antioxidants are warranted for PsA. Taking anti-ros suPPlements does
help.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16805955
Oxidative stress parameters in different systemic rheumatic diseases.
Firuzi O, Fuksa L, Spadaro C, Bousova I, Riccieri V, Spadaro A,
Petrucci R, Marrosu G, Saso L.
Dipartimento di Fisiologia Umana e Farmacologia "Vittorio Erspamer",
Universita di Roma "La Sapienza", Italy.
The involvement of oxidative stress in the pathogenesis of rheumatic
disorders, such as systemic sclerosis (SSc) and chronic
polyarthritides, has been suggested yet not thoroughly verified
experimentally. We analysed 4 plasmatic parameters of oxidative stress
in patients with SSc (n = 17), psoriatic arthritis (PsA) (n = 10) and
rheumatoid arthritis (RA) (n = 9) compared with healthy subjects (n =
22). The biomarkers were: total antioxidant capacity (TAC) measured by
ferric reducing antioxidant power (FRAP) method, hydroperoxides
determined by ferrous ion oxidation in presence of xylenol orange (FOX)
method and sulfhydryl and carbonyl groups assessed by
spectrophotometric assays. The results showed ______significantly
increased____ hydroperoxides____ in SSc, ___PsA___ and RA (3.97 +/-
2.25, 4.87 +/- 2.18 and 5.13 +/- 2.36 mumol L(-1), respectively)
compared with the control group (2.31 +/- 1.40 mumol L(-1); P < 0.05).
Sulfhydryls were significantly lower in SSc (0.466 +/- 0.081 mmol
L(&minus1)), PsA (0.477 +/- 0.059 mmol L(-1)) and RA (0.439 +/- 0.065
mmol L(-1)) compared with the control group (0.547 +/- 0.066 mmol
L(-1); P < 0.05). TAC in all three diseases showed no difference in
comparison with controls. Carbonyls were significantly higher in RA
than in the control group (32.1 +/- 42 vs 2.21 +/- 1.0 nmol (mg
protein)(-1); P < 0.05). The obtained data indicate augmented free
radical-mediated injury in these rheumatic diseases and suggest a role
for the use of antioxidants in prevention and treatment of these
pathologies.
PMID: 16805955
(((((((((((((((((((((((((((((((((((((((((()))))))))))))))))))))))))))))))))))))))))))))))
Yesterdays post on minerals, brought uP my usage of IP6.
This is that post from yesterday,
http://groups.google.com/groups/search?q=16804013+zinc+copper&qt_s=Search
What am i doing to myself by taking IP6? Am I chelating excess zinc,
copper, iron etc?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16522929
Predicting bioavailable zinc from lower phytate forms, folic Acid and
their interactions with zinc in vegetarian meals.
Chiplonkar SA, Agte VV.
Agharkar Research Institute, G G Agarkar Road, Pune 411 004, India.
shas...@indiainfo.com
OBJECTIVE: To develop a statistical model for predicting zinc
bioavailability from cereal-based vegetarian meals using relative
proportion of nutrients, non-nutrients and their interactive effects.
METHODS: A database on in vitro zinc dialysability (by isotopic tracer,
65Zn) of vegetarian meals (266 out of 326) from Asia, Africa, Europe
/US and Latin America was used to develop a model for estimating zinc
bioavailability. A multiple regression analysis adjusted for energy
content was carried out for net bioavailable zinc from a meal with the
predictor variables as meal contents of iron, zinc, copper, ascorbic
acid, beta-carotene, riboflavin, thiamine, folic acid, tannic acid,
fiber, phytate degradation products (IP6 to IP1), along with their
interaction terms. Reproducibility of the model was tested with
remaining 60 meals. Validation of the model was done with zinc
absorption data of i) 12 young adults on 24 meals and ii) 5 adults with
ileostomy on 7 meals. RESULTS: Folic acid, IP3 and IP5 were significant
influencing factors for bioavailable zinc. Weighted multiple regression
equation was: ln (bioavailable zinc in mg) = -1.701 + 1.285 x ln [(IP5
in mg] x (Zn in mg)] -1.222 x ln(IP5 in mg) -0.0078 x folic acid in
microg -0.137 x ln [(IP3 in mg) x (Zn in mg)] with adjusted R--[2] =
0.64, p = 0.0001. The correlation between predicted and observed
dialysability of meals was found to be 0.96 (p < 0.01). A significant
correlation between observed and predicted amount of absorbed zinc (r =
0.85, p < 0.01) was obtained for the human data of zinc absorption in
12 healthy and 5 subjects with ileostomy. CONCLUSIONS: Bioavailable
amount of zinc from vegetarian meals was influenced by IP3, IP5 and
folic acid content and their interactive effect with zinc content.
PMID: 16522929
Taking IP6 is lowering zinc, copper and lipids!
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=10625943
Inositol hexaphosphate (IP6) as an anti-neoplastic and lipid-lowering
agent.
Jariwalla RJ.
California Institute for Medical Research, Santa Clara Valley Medical
Center, San Jose 95128, USA.
IP6, a major dietary source of inositol phosphates, is a physiological
antioxidant with potential to form complexes with cations linked to
cell proliferation and hypercholesterolemia. Accordingly, we have
examined the action of IP6 on dietary modulation of neoplasia and
hyperlipidemia in a Fischer rat model (1, 2). Two studies were
conducted on the effects of naturally-derived IP6, administered as
purified phytate, a salt form of phytic acid (inositol hexaphosphoric
acid). One study examined the effect on the growth of tumors promoted
in syngeneic rats transplanted with a viral oncogene-transformed cell
line. Increases in tumor incidence and growth rate of fibrosarcomas
seen following administration of a special diet (containing 5%
saturated fatty acids and 1.2% magnesium oxide) were completely
mitigated by supplementation of the same diet with purified
potassium-magnesium phytate (8.9% phytic acid by weight). The other
study examined the IP6 effect on serum lipid and mineral levels in
animals fed a cholesterol-enriched or standard diet. Elevated levels of
serum total cholesterol, triglycerides and zinc/copper ratio associated
with administration of the cholesterol-enriched diet were
_____significantly lowered_______ by supplementation of this diet with
monopotassium phytate. Addition of monopotassium phytate to the
standard diet also reduced serum lipid levels but did not significantly
affect the zinc/copper ratio. These studies support a role for IP6 as a
potential therapeutic agent in the treatment of cancer and
hyperlipidemia.
PMID: 10625943
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16401188
Using IP6 to beat back cancer has become an alternative treatment of
sorts. Read the second half of this link from Bill Sardi,
http://www.knowledgeofhealth.com/report.asp?story=Cancer%20Regimen&catagory=Cancer,%20Vitamin%20D
& [ all of this one ]
http://www.knowledgeofhealth.com/report.asp?story=The%20IP6%20Rice%20Bran%20Cleanse&catagory=Chelation,%20IP6
According to the first link 1000 mg's a day is a support dosage. I take
one 500 mg a day first thing in the mornings
at least half hour before meals (my shake).
But what about cancer folks? Here's one area their looking at,
non-homologous end-joining (NHEJ) with IP6
http://www.jhsph.edu/publichealthnews/magazine/archive/Mag_Fall04/microcosmos/enemy_within.html
[...]
She discovered that, in a test tube, IP6 stimulated the NHEJ pathway.
<sniP>
For psoriatics i'm of the opinion that it lowers copper/zinc ratios, as
well as lowering iron stores that lead to the need for antioxidants
(anti-ROS).
Here's a link in agreement from the folks in Japan that make this
stuff.
http://www.thehormoneshop.com/ip6.htm
[...]
Natural components extracted from brown rice germ reportedly activate
cells and enhance immunity. "In vivo (In the body) at least, the
remarkable affinity of InsP6 for iron totally inhibits this metal's
ability to catalyze the formation of hydroxyl radicals."(See note
below) In other words IP6 grabs a hold of free Iron in the system and
by a process of Chelation gets rid of it and its ability to form free
radicals that cause oxidation and aging.
[...]
In Japan it is known to remove active oxygen in the body, suppressing
lipid peroxide production and absorbs excess iron ions, having an
effect on heart disease, liver dysfunction, dermatitis and other
pathologic conditions caused thereby.
(randall note: Damn, i am turning Japanese! Pass the brown rice with
raw tuna please!)
(half way down the last link. Under heart disease)
The same
study demonstrated that dietary IP6 caused a lowering of the
zinc/copper
ratio, a marker of hypercholesterolemia, without significantly
affecting
levels of other minerals in serum. This lipid-lowering action of IP6
was seen
at dosages (upto 9% of the diet) that were free of adverse side effects
in the
tested animals.
<sniP>
Is wasabi anti-ros?
Yep!
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16256955
Inhibition of lipopolysaccharide-induced cyclooxygenase-2 transcription
by 6-(methylsulfinyl) hexyl isothiocyanate, a chemopreventive compound
from Wasabia japonica (Miq.) Matsumura, in mouse macrophages.
Uto T, Fujii M, Hou DX.
Department of Biochemical Science and Technology, Faculty of
Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima City
890-0065, Japan.
6-(Methylsulfinyl)hexyl isothiocyanate (6-MITC) is a chemopreventive
compound occurring in Wasabi (Wasabia japonica (Miq.) Matsumura), which
is a very popular pungent spice in Japan. We investigated the effects
of 6-MITC on the expression of cyclooxygenase-2 (COX-2) in
lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells.
Treatment with 6-MITC suppressed LPS-mediated induction of COX-2
protein in a dose-dependent manner. Transfections with various COX-2
promoter reporter constructs revealed that the inhibitory effects of
6-MITC on COX-2 gene expression were directed by the core promoter
elements including nuclear factor kappaB (NF-kappaB),
CCAAT/enhancer-binding protein (C/EBP) and cyclic AMP-response element
(CRE) sites. Western blotting analysis showed that 6-MITC inhibited
LPS-induced activation of MAPK (ERK, p38 kinase and JNK) and
transcriptional factors (CREB, c-Jun and C/EBPdelta) binding the core
elements of COX-2 promoter, substantiating the involvement of these
signal transduction pathways in the regulation of COX-2 expression by
6-MITC. Moreover, Western blotting experiments with MAPK-specific
inhibitors (U0126 for MEK1/2, SB203580 for p38 kinase and SP600125 for
JNK) demonstrated that 6-MITC suppressed LPS-induced COX-2 expression
by blocking the activation of JNK-mediated AP-1 and ERK/p38
kinase-mediated CREB or C/EBPdelta. Finally, the structure-activity
study revealed that the inhibitory potency of methylsulfinyl
isothiocyanates (MITCs) depended on the methyl chain length. These
findings demonstrate for the first time that 6-MITC is an effective
agent to attenuate COX-2 production, and enhance our understanding of
the anti-inflammation properties of 6-MITC.
PMID: 16256955
And the lovely tasting condiment is anti-cox2. Wahoo!
Now, if we can raise ceramides naturally in the skin, lower Th1 levels
as well and
use IP6 to take down coPPer levels and fix the gut to produce more
IL-10,
we all can clear uP a lot.
Fixing the gut with www.thewholewhey.com comes first!
Then using these other tiPs can keep you on the right track for a life
time of clear skin!
randall... been there, done that and working to refine it!
randall
Duplicating this next break through for psoriasis would be a major
couP!
WE do share common inflammatory pathways with type one diabtes.
http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=13853
Gene Therapy and Preventing Diabetes
(Ivanhoe Newswire) -- A recent study at the University of Pittsburgh
revealed gene therapy could serve as a means of preventing type 1
diabetes in those who are genetically susceptible to the disease.
Type 1 diabetes, formerly known as juvenile diabetes, affects more than
700,000 Americans and can cause health difficulties like blindness,
heart disease, kidney failure and nerve damage.
In the study, researchers inserted a gene into non-obese diabetic (NOD)
mice that encoded for a protein called cytokine, which is responsible
for the transition of immune cells becoming insulin-producing cells.
This allowed researchers to prevent hyperglycemia, more commonly known
as high blood sugar, in the mice.
The genes were sent via an adeno-associated virus that inserted genes
for one of two cytokines, interleukin-4 (IL-4), which was found to
prevent hyperglycemia or interleukin-10 (IL-10), which was found to
bring about hyperglycemia more quickly.
"Although the exact mechanism is still under investigation, we believe
the protection we observed in our study is due to IL-4 stimulating an
increase in regulatory T cells, which are known to suppress the
activation of the immune system," reports Khaleel Rehman Khaja, Ph.D.,
senior research associate, University of Pittsburgh School of Medicine.
According to Dr. Khaja, the finding that researchers can successfully
insert genes into a live organism and observe their effects on type 1
diabetes was the most significant part of the study.
This article was reported by Ivanhoe.com, who offers Medical Alerts by
e-mail every day of the week. To subscribe, go to:
http://www.ivanhoe.com/newsalert/
-----------------------------------------
Isn't that a surprise.
Type I diabetes, like psoriasis is a Th1 disease.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16704296
Nicotinamide reduces high secretion of IFN-gamma in high-risk relatives
even though it does not prevent type 1 diabetes.
Hedman M, Ludvigsson J, Faresjo MK.
Division of Paediatrics & Diabetes Research Centre, Department of
Molecular & Clinical Medicine, Faculty of Health Sciences, Linkoping
University, Linkoping, Sweden.
Type 1 diabetes (T1D) is an autoimmune disease suggested to be of a T
helper (Th)1-like origin. This study aimed to investigate the Th1-like
and Th2-like profile in high-risk individuals during the prediabetic
phase and the immunologic effect of treatment with nicotinamide.
High-risk first-degree relatives of T1D patients participating in the
European Nicotinamide Diabetes Intervention Trial (ENDIT) were treated
with either nicotinamide or placebo. Peripheral blood mononuclear cells
(PBMC) were obtained during the prediabetic phase and close to the
onset of manifest T1D and from nondiabetic high-risk individuals. Using
the sensitive enzyme-linked immunospot (ELISPOT) technique to
distinguish Th1-like from Th2-like lymphocytes, secretion of
interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was analyzed from
PBMCs spontaneously and after in vitro stimulation with the
diabetes-associated autoantigens, glutamic acid decarboxylase 65
(GAD65, protein and peptide, aa 247-279), recombinant tyrosine
phosphatase (IA-2), and heat shock protein (HSP, aa 437-460). High-risk
individuals showed high spontaneous as well as autoantigen-induced
IFN-gamma secretion. Secretion of IFN-gamma and the IFN-gamma/IL-4
ratio, induced by autoantigens, decreased in individuals developing T1D
(p < 0.05), whereas nondiabetic individuals showed an increased IL-4
response (p < 0.05). Thus, a Th1-dominated cytokine profile observed in
high-risk individuals inclined toward a diagnosis of diabetes.
Nicotinamide caused decreased spontaneous (p = 0.05) and in vitro
autoantigen-induced IFN-gamma secretion (p < 0.05) and may play a role
in immune regulation, even though it has not been shown to prevent T1D.
PMID: 16704296
And nicotinamide doesn't/hasn't slowed psoriasis much in my trials.
But what is interesting is when Th1/Th2 skews show up simultaneously in
autoimmune (Ai or I.M.I.D.) conditions.
TH1/TH2 cytokine balance in patients with both type 1 diabetes mellitus
and asthma.
Marianna R, Olga B, Tzvi B, Naomi W, Regina O, Nira KM, Rapoport MJ.
Department of Pediatrics, Assaf Harofeh Medical Center, Sackler Faculty
of Medicine, Tel-Aviv University, Israel.
BACKGROUND AND OBJECTIVE: T1DM and asthma are mediated by opposite arms
of the cellular immune system namely T helper (Th)1 and Th2 CD4(+)
cells, respectively. Our aim was to characterize the Th1/Th2 cytokine
balance in patients with both T1DM and asthma. METHODS: Forty-four
patients, mean age 19 years were matched by gender and age, to 4 paired
groups: T1DM and asthma, asthma only, T1DM only and healthy controls.
Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with
disease-specific recombinant antigens; glutamic acid decarboxylase and
house dust mite (Der p1 antigen) for T1DM and asthma, respectively, and
non-specific mitogens; phytohemaglutinin (PHA), tetanus toxin and
anti-CD3 mAb. ELISPOT and ELISA technique were used to determine
INF-gamma, IL-2, IL-4, IL-13 and IL-10 expression. RESULTS: Patients
with T1DM and asthma demonstrated a similar cytokine pattern but lower
Th1/Th2 ratio compared to patients with T1DM only. The Th2 cytokines
response to Der p1 was enhanced in patients with both diseases compared
to controls. The IL-10 overall secretion was higher in patients with
both diseases compared to one disease only. CONCLUSION: The Th1 and Th2
secretory pattern of patients with T1DM and asthma combines features of
both diseases suggesting a unique Th1/Th2 balance.
PMID: 16765604
I was going from one Th2 atopic problem after another till i onset at
an
early age with Th1 psoriasis.
Finding the connections between the two should help to cure them both.
:)
============================================
Here's more fuel for the fires.
http://www.newswise.com/articles/view/521661/
Lab Scientists Tame Overactive CF Protein
Description
A team led by Johns Hopkins Children's Center scientists has
identified and successfully tamed an overactive protein that plays a
key role in cystic fibrosis (CF), a genetic disorder that interferes
with the body's ability to transport chloride in and out of cells.
Newswise - A team led by Johns Hopkins Children's Center scientists
has identified and successfully tamed an overactive protein that plays
a key role in cystic fibrosis (CF), a genetic disorder that interferes
with the body's ability to transport chloride in and out of cells.
Using a tool called RNA interference on cells in the laboratory,
researchers successfully intercepted signals sent out by the rampant
protein and prevented cell damage by the protein, effectively restoring
the cell to normal.
"The hope is that these findings will be used to design therapies and
drugs that go beyond symptom management and actually restore normal
cell function to prevent CF," says senior investigator Pamela
Zeitlin, M.D., a pulmonologist at the Children's Center, although she
warned that they are years from developing or testing such treatments
in whole animals or people. A report on the work from scientists at the
Children's Center and the University of Maryland appears in the June
23 issue of the Journal of Biological Chemistry.
The overactive protein, called VCP/pr 97 (valosin containing protein),
kills a chloride transporter in the cells of the vast majority of CF
patients, but quieting the protein restores the cells' ability to
transport chloride in and out, researchers found. The inability to
transport chloride is the hallmark of CF that causes dangerous buildup
of thick, sticky mucous in several organs, including the pancreas and
the lungs, leading to malnutrition, chronic lung infections and lung
damage.
Cells have a built-in quality-control machinery called ERAD
(endoplasmic reticulum-associated degradation), which chemically
"marks" defective proteins for destruction and sends them to the
cell's waste-disposal complex, called the proteasome. In people with
CF, defects in genes for a protein called CFTR (cystic fibrosis
transmembrane regulator) interrupt the transport chemistry. Until now,
researchers had not identified the precise search-and-destroy proteins
that ERAD deploys to seek out the mutant CFTR.
"We were able to confirm that to get rid of the defective CFTR
protein, cells deploy VCP/p97 protein, which latches onto the damaged
CFTR and sends it to the proteasome for destruction," Zeitlin says.
"Using RNA interference, which basically works by silencing the
expression of genes or proteins, we homed in on VCP and blocked its
production. That let the defective CFTR to successfully sneak past the
quality control and race up to the surface."
To determine VCP's role in the destruction of CFTR, researchers
compared bronchial cells from CF and non-CF patients. In non-CF cells,
the protein's levels were in check, whereas they were strikingly high
in cell samples obtained from CF patients.
Suspecting that inhibiting VCP would spare the chloride-transporting
channels from premature demise, the team showed that when the VCP's
level was lowered, it no longer destroyed CFTR.
In a second set of tests, researchers blocked the destruction of CFTR
with a proteasome-inhibiting drug currently used to treat multiple
myeloma. Silencing the protein by the use of RNA interference was
superior to the proteasome inhibitor, researchers found.
Both the drug and RNA interference also staved off inflammation caused
by cytokine IL8, which is the main inflammatory chemical produced by CF
damaged cells.
"Targeting VCP, we were able to achieve two things at once --
restoring chloride channel function and curbing inflammation" says
co-author Neeraj Vij, Ph.D., a postdoctoral fellow at the Children's
Center. "Inhibiting specific sites in VCP can lead to the development
of CF drugs."
"The goal is to develop small molecules that disrupt the binding
between the VC protein and CFTR, much like tiny guided missiles that
take out portions of this rampant VC protein before it latches onto
CFTR," Zeitlin says.
Authors on the paper are Zeitlin and Vij, of Hopkins, and Shengyun
Fang, M.D., Ph.D., of the University of Maryland Biotechnology
Institute.
Founded in 1912 as the children's hospital of the Johns Hopkins
Medical Institutions, the Johns Hopkins Children's Center offers one
of the most comprehensive pediatric medical programs in the country,
from performing emergency trauma surgery, to finding causes and
treatments for childhood cancers, to delivering a child's good bill
of health. The Johns Hopkins Children Center's Pediatric Trauma
Service is Maryland's only state-designated trauma center for
children. With recognized Centers of Excellence in 20 pediatric
subspecialties including cardiology, transplant, psychiatric illnesses
and genetic disorders, Children's Center physicians, nurses and staff
provide compassionate care to more than 90,000 children each year. For
more information, please visit: http://www.hopkinschildrens.org
or
http://en.wikipedia.org/wiki/Cystic_fibrosis
=================================
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=16702334
The nutritional relationship linking sulfur to nitrogen in living
organisms.
Ingenbleek Y.
Laboratory of Nutrition, Faculty of Pharmacy, University Louis-Pasteur,
Strasbourg, France. in...@pharma.u-strasbg.fr
Nitrogen (N) and sulfur (S) coexist in the biosphere as free elements
or in the form of simple inorganic NO3- and SO4(2-) oxyanions, which
must be reduced before undergoing anabolic processes leading to the
production of methionine (Met) and other S-containing molecules. Both N
and S pathways are tightly regulated in plant tissues so as to maintain
S:N ratios ranging from 1:20 to 1:35. As a result, plant products do
not adequately fulfill human tissue requirements, whose mean S:N ratios
amount to 1:14.5. The evolutionary patterns of total body N (TBN) and
of total body S (TBS) offer from birth to death sex- and age-related
specificities well identified by the serial measurement of plasma
transthyretin (TTR). Met is regarded as the most limiting of all
indispensable amino acids (IAAs) because of its participation in a
myriad of molecular, structural, and metabolic activities of survival
importance. Met homeostasis is regulated by subtle competitive
interactions between transsulfuration and remethylation pathways of
homocysteine (Hcy) and by the actual level of TBN reserves working as a
direct sensor of cystathionine-beta-synthase activity. Under
steady-state conditions, the dietary intake of SO4(2-) is essentially
equal to total sulfaturia. The recommended dietary allowances for both
S-containing AAs allotted to replace the minimal obligatory losses
resulting from endogenous catabolism is largely covered by Western
customary diets. By contrast, strict vegans and low-income populations
living in plant-eating countries incur the risk of chronic N and Met
dietary deficiencies causing undesirable hyperhomocysteinemia best
explained by the downsizing of their TBN resources and documented by
declining TTR plasma values.
PMID: 16702334
OK. Lets find more on this last one.
http://www.transthyretin.com/
&
http://www.emedicine.com/med/topic3365.htm
When one doesn't eat a balanced diet things will go wrong.
Look at us psoriatics. Most of us are over not underfed.
Yet we look for a suPPlement to toP off/fix the X pathway, the latest
being
ceramides.
Will juicing up with ceramide cure one of us?
randall...time will tell.. don't hold your breath.
randall
Hi,
P news from around the world. Slow day. Happy 4th!
http://www.dailyrecord.com/apps/pbcs.dll/article?AID=/20060703/COMMUNITIES/607030304/1203/NEWS01
[...]
Morr has one of the most severe forms of the disease, and recalls
fighting it early in his childhood.
When he was 6, Morr's parents took him to Columbia University's New
York-Presbyterian Hospital for a tar and light treatment. The doctors
put cold tar on Morr's body then subjected him to ultraviolet lights,
hoping that would make a difference on his peeling skin and reddened
face.
"It didn't help the condition; it didn't make it look better,"George
Morr, Robert's father, of Belvidere said.
Alternative to gym
Throughout his school years, Morr got permission to do an activity
other than gym, his mother said. He didn't want to take his shirt off
because he would be the instant butt of jokes.
"His arms were very scaly at times," Alice Morr said. "A lot of the
children would be afraid to go near him. They would call him,
'Snowflake.' Children can be very cruel at some times. Children that
are obese go through the same thing he goes through."
Year after year, his parents tried a variety of treatments. Many of the
treatments were experimental, so it didn't put too much of a financial
strain on the small family living in the Pine Brook section of
Montville, Alice Morr, his mother said.
Solar treatment
Perhaps the most effective way to treat the symptoms of the disease is
exposure to sun, said Michael Paranzino, of Psoriasis Cure Now, based
in Kensington, Md.. But that type of treatment is also one of the most
anguishing things for patients to do, he said.
[...]
Psoriasis Cure Now, which aims to have victims of the disease be more
vocal about demanding federal medical research to find a cure, recently
launched a campaign calling on Google to stop display ads that
advertise what Paranzino called false hopes of cures for the disease
and "enforce its own corporate policy against accepting advertisements
that promote phony cures for incurable diseases."
Last year in March, Psoriasis Cure Now asked 1,000 lawmakers and 1,000
journalists in the healthcare field to view images of patients with the
disease as a way to press for increased funding on research into the
disease. Some of these images, on the group's Web site
www.psoriasiscurenow.org, are harrowing.
According to the National Institute of Health, between 5.8 million and
7.5 million people in the United States have psoriasis. Two-thirds of
that number have a moderate form of the disease. One-third have severe
forms, which is the category Morr falls under.
"They suffer in silence,"Paranzino said. <end>
--------------------------------------
What's cold tar? Like cold cream? <g>
Snowflake isn't so bad, once your clear. <w>
--------------------------------------------------------------
http://www.abc.net.au/news/newsitems/200607/s1677503.htm
'Magic bullets' to attack rogue 'godfather' genes
Researchers at the University of New South Wales want to be the first
to conduct trials on humans using a new class of medication known as
"smart drugs".
The experimental drug the researchers have created is DNA-based.
They say it attacks the "godfather" of rogue genes, which is behind a
wide range of illnesses from skin cancers to arthritis and diseases of
the eye and heart.
"These are magic bullets that we've developed," Professor Levon
Kachigian said.
"These are small bits of either DNA or RNA that have been custom made
to focus on these bad genes, these godfather genes or these master
regulators."
So far, the drug has only been tested on mice.
The university's Professor Bernard Stewart says early next year they
hope to test it on 10 people with skin cancer.
"The material has been synthesised and tested in animal systems," he
said.
"When it was used in that context, the growth of tumours in these
particular animal models was markedly reduced."
The same kind of technology has also shown positive results in treating
heart attacks.
Currently there are two options for treating heart attacks: either clot
busting drugs to clear blockages in arteries; or the use of stints -
tiny balloons to reopen the arteries.
Cardiologist Dr Ravinay Bhindi says this drug could do that and reduce
damage.
"We've been able to reduce heart attack size by up to 50 per cent
through the delivery of these gene specific targeting therapies through
the interruption of these processes, these negative processes that the
gene controls," he said.
"These findings are exciting and are being explored in further
studies."
The researchers preliminary findings were today published in Nature
Biotechnology.
Professor Kachigian expects there to be world wide interest when their
trials get under way.
"Nobody else has, as yet, trialled DNA-based drugs of the molecular
assassins that I talked about today in humans to this point," he said.
"And so we are, while we look with great excitement to the possibility
of showing the efficacy of these agents in the clinic, we're also very
mindful of potential down sides to their use."
-------------------------------------------------
This email I received from a fellow skin sufferer.
"Randall,
In your last email, May 4, you said you wanted to post details of my
AMC topical treatment of skin lesions to your psoriasis group. I have
not seen it in your alt psoriasis postings and wonder whether you may
have changed your mind.
I have had three cases of psoriasis, if they were psoriasis, treated
with AMC.
1) One was the man who had multiple red itchy areas over his body
diagnosed by his doctor as psoriasis. He was provided with AMC and
brushed it on in an uncontrolled schedule. He reported that the next
day the itching was gone and some areas showed signs of fading. Now
about two years later he says most spots have completely cleared, the
others have cleared over most of the spot areas and AMC was the only
treatment that has been effective. I regret the treatment was not
controlled. I believe his affliction was not psoriasis.
2) A woman had a slightly painful shiny scaly area on a finger
diagnosed as contact dermatitis, but which I think was psoriasis. After
shorter initial AMC treatments she applied AMC twice a day for two
weeks when all signs of the lesion had disappeared. The area remained
clear of lesion for about three months when the original lesion
recurred. I will see the woman on my drive north in two weeks and
encourage her to repeat the AMC treatment followed by a maintenance
schedule of two AMC applications one day each week for several months.
Please tell me how you are applying IP6 to your psoriasis.
regards, Ernest
Keywords: 5-Fu, DMSO, Efudex
My reply is private. :)
But I take IP6 (500 mg.s) from Jarrow once
a day. Half hour before meals, first thing in the morning. :)
It's almost been one year of continous use. My longest trial
with it to date.
I really believe it helps and maybe that's why it does!
----------------------------------------------------------------------------
For those of you, like Ben who may be interested in Ernests
application.
You can see the links right here,
http://groups.google.com/groups/search?q=ernest+dmso+efudex&qt_s=Search
---------------------------------------------------
randall... Join the NPF or psorcurenow and make a BANG
Plantmistress
http://www.sciam.com/article.cfm?chanID=sa004&articleID=0006ED18-FBC3-1492-BAAC83414B7F0000&ref=rss
Here is the text of the article.
July 03, 2006
BIOLOGY
An Immune Portal
Protein may be a key to autoimmune disorders
By Jeneen Interlandi
As a medical student in Germany, Stefan Feske studied two Turkish
brothers born with severe combined immunodeficiency syndrome, or SCIDS,
a rare, life-threatening genetic disease characterized by a seriously
debilitated immune system. Because the boys' T cells could not take up
calcium, their immune systems would not work. These siblings provided
Feske and his collaborators with a unique opportunity to track down a
key protein involved in this process by studying human cells in which
it was already dysfunctional. "You cannot do this for every gene hunt,"
says Feske, now an assistant professor of pediatrics at Harvard Medical
School.
That search ended recently with the discovery by Feske and his Harvard
collaborators, Anjana Rao and Yousang Gwack, of Orai 1, a protein that
may be part of the ion channel that admits calcium into T cells, a step
required to set the body's immune response in motion. The group's
endeavors, reported in the May 11 issue of Nature, represent several
years of investigations that were part of a larger 20-year effort to
track down this critical cog in immune functioning.
Because the pathway that this channel participates in has been
conserved throughout evolution, fruit flies and humans still make and
use many of the proteins involved in much the same way. Recognizing
this similarity, Gwack, now a research associate in pathology at
Harvard, developed a genetic screen in fruit flies that complemented
Feske's patient studies. By expressing a key human protein in fruit fly
cells, Gwack was able to search for the elusive calcium channel in the
fly's smaller genome. His data, combined with a genetic analysis of the
siblings' extended family, led the team to a single gene that was
mutated in both patients. Gwack named the new protein encoded by the
gene Orai 1, after the keeper of heaven's gate in Greek mythology.
Ion channels facilitate the movement of specific molecules, such as
calcium or potassium, into and out of cells. Because these proteins
span the cell membrane, they make a particularly appealing target for
finding new drugs. "The problem for most drugs is that they have to get
into the cell," Feske says. Getting into a cell means getting past its
membrane, something ion channels were made to accomplish.
Drug companies around the world have been searching for ion channels
specific to the immune system, especially a particular calcium channel,
whose genetic identity has evaded researchers for two decades. The
discovery of Orai 1, which may be a subunit of the immune system's
calcium channel, represents a major breakthrough in that initiative.
"The impact is going to be huge," says Michael Xie, director of
ion-channel research at Synta Pharmaceuticals in Lexington, Mass.,
which is developing drugs that interact with this calcium channel.
"Inhibition of this immune channel could provide one of the most direct
means of manipulating the immune response."
Because drugs that block this passageway would stifle the body's immune
response, they could be useful in treating a variety of autoimmune
disorders, such as allergies and rheumatoid arthritis, which occur when
the body's immune system turns against itself. Scientists also hope
further research on Orai 1 will lead to better drugs for preventing
transplant rejection, which occurs when the immune system attacks a
donor organ. Drugs that home in on this apparently immune-specific
calcium channel could avoid side effects, such as kidney impairment and
neurotoxicity, caused by other transplant drugs, which interact with
molecules found in several types of cells.
Still, more work remains before scientists can be certain of the role
that Orai 1 plays. It is possible, for example, that the newly
discovered protein is not a component of the channel itself but rather
a modulator, or key, that opens and closes the channel like a doorway.
And even if Orai 1 turns out to be a channel protein, it may be only
one of the components that makes up the channel. "It's not the end of
the story," Gwack says. "But the whole field is getting very, very hot
now."
randall
Plantmistress wrote:
> I saw this article on the Scientific American website
>
> http://www.sciam.com/article.cfm?chanID=sa004&articleID=0006ED18-FBC3-1492-BAAC83414B7F0000&ref=rss
>
<sniP>
Great find!
Of course there isn't much we can turn uP on it yet.
I'll try!
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16582901
A mutation in Orai1 causes immune deficiency by abrogating CRAC channel
function.
Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan
PG, Lewis RS, Daly M, Rao A.
The CBR Institute for Biomedical Research, and the Department of
Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston,
Massachusetts 02115, USA.
Antigen stimulation of immune cells triggers Ca2+ entry through Ca2+
release-activated Ca2+ (CRAC) channels, promoting the immune response
to pathogens by activating the transcription factor NFAT. We have
previously shown that cells from patients with one form of hereditary
severe combined immune deficiency (SCID) syndrome are defective in
store-operated Ca2+ entry and CRAC channel function. Here we identify
the genetic defect in these patients, using a combination of two
unbiased genome-wide approaches: a modified linkage analysis with
single-nucleotide polymorphism arrays, and a Drosophila RNA
interference screen designed to identify regulators of store-operated
Ca2+ entry and NFAT nuclear import. Both approaches converged on a
novel protein that we call Orai1, which contains four putative
transmembrane segments. The SCID patients are homozygous for a single
missense mutation in ORAI1, and expression of wild-type Orai1 in SCID T
cells restores store-operated Ca2+ influx and the CRAC current
(I(CRAC)). We propose that Orai1 is an essential component or regulator
of the CRAC channel complex.
PMID: 16582901
It's a crac thing. LOL.... figures!
Lets find the protein.
This must be the right one.
http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=protein&val=97180269
Here are the other 10 choices,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein&cmd=search&term=orai+1
On the web,
http://www.google.com/search?hl=en&lr=&q=orai+immune+ca&btnG=Search
&
http://www.google.com/search?hl=en&lr=&q=orai+immune+ca2%2B&btnG=Search
I see NFAT,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=nfat&start=0&filter=0
&
http://www.panomics.com/NFAT.cfm
Calcium ions and psoriasis,
http://groups.google.com/groups/search?hl=en&lr=&q=psoriasis+immune+ca2%2B&qt_s=Search
All in all, looks like another piece of the jigsaw puzzle. :~)
randall... what's not to like? When your on the right path?
randall
P news from around the world.
This next one was reported on in 2004 and 2005 with
P mice trials. (link follows the subject story)
Will 2006 be their year? Can they dial the drug in
for psoriatic people? How many mice ate the big one?
Did anyone get an elephant head like those guys in England?
Can you think of a reason to avoid the trials?
http://www.newswise.com/articles/view/521716/
Drug Dials Down the Energy within Cells
Newswise - A drug effective at treating animal models of human
autoimmune disorders and other diseases works by dialing down the
activity of a key enzyme involved in energy production, University of
Michigan researchers have found.
"Many drugs block the function of enzymes, essentially turning them
off," said Gary Glick, who is the Werner E. Bachmann Collegiate
Professor of Chemistry at U-M. "Our compound works more like a volume
control, so we're able to dial enzyme activity down to a level that
maintains normal function while simultaneously allowing for initiation
of a process that selectively kills or disables disease-causing cells."
Glick and collaborators published their findings in the June 16 issue
of ACS Chemical Biology.
The drug, discovered by Glick and coworkers and called
benzodiazepine-423 (Bz-423), is a chemical cousin of anti-anxiety
medications such as Valium and Xanax. In previous work, Glick's group
showed that Bz-423 reduces effects of arthritis and the autoimmune
disease lupus in mice and _may be_ useful in treating psoriasis. Unlike
conventional drugs for these conditions, which can't discriminate
between healthy and disease-causing cells, Bz-423 is highly selective,
homing in on disease-causing cells.
In an attempt to better exploit its therapeutic properties, the
researchers have been studying the details of Bz-423's activity. They
learned that the compound targets an enzyme inside mitochondria, the
energy factories of cells. The specific enzyme, F1F0-ATPase, is
responsible for producing most of the cell's ATP. That's a critical
role because ATP, often referred to as the cell's energy currency, is
the molecule that captures chemical energy from food and transfers it
to energy-demanding processes, such as muscle contraction and the
transmission of nerve signals.
"People had proposed in the past that if you could inhibit this enzyme,
there might be therapeutic potential. But the problem is, if you
inhibit the enzyme in the way most powerful drugs do, turning it off,
you deplete the cell of ATP, and that's fatal," Glick said. "Our new
work reveals the mechanism by which Bz-423 inhibits the enzyme while
still allowing it to function. This is important because it suggests
principles that may be useful for targeting other bioenergetic
pathways. Now we have some rules that we can apply to be able to
modulate the mitochondria in new ways that could be therapeutic."
Ultimately, the findings may have applications not only for lupus,
arthritis and psoriasis, but also for other conditions, Glick believes.
"There are other diseases---certain cancers and a number of other
immune diseases---where we think the way the cells make and utilize
energy is fundamental to the disease process. Combining that knowledge
with our new knowledge of how to regulate the energy of the cell could
open up new avenues for treating disease and monitoring the
effectiveness of treatment."
Glick collaborated on the research with Carol Fierke, who is the Jerome
and Isabella Karle Collegiate Professor of Chemistry; Anthony Opipari,
Jr., associate professor of obstetrics and gynecology; graduate student
Kathryn Johnson and postdoctoral fellow Joanne Cleary. The researchers
received funding from the National Institutes of Health.
For more information:
Gary Glick---http://www.chembio.umich.edu/people/glick.html
ACS Chemical Biology---http://pubs.acs.org/journals/acbcct/index.html
Previous news releases about Bz-423:
"New compound holds promise for treating lupus and related diseases"---
http://www.umich.edu/news/index.html?Releases/2002/Oct02/chr101602a
"Novel drug fights autoimmune disorders"---
http://www.umich.edu/news/index.html?Releases/2003/Mar03/r030303c
"Chemical cousin of anti-anxiety drugs holds promise for psoriasis
treatment"---
http://www.umich.edu/news/index.html?Releases/2004/Dec04/r120804a
___________________________________________
>From the previous years 04 and 05.
http://groups.google.com/groups/search?q=benzodiazepine-423+%28Bz-423%29&qt_s=Search
And looking at these 12 hits and the author glick. His most recent
trial,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16488147
Identification of cytotoxic, T-cell-selective
1,4-benzodiazepine-2,5-diones.
Francis TM, Sundberg TB, Cleary J, Groendyke T, Opipari AW Jr, Glick
GD.
Chemical Biology Graduate Program, University of Michigan, Ann Arbor,
MI 48109-1055, USA.
A family of 1,4-benzodiazepine-2,5-diones (BZDs) has been synthesized
and evaluated against transformed B- and T-cells for lymphotoxic
members. A large aromatic group on the C3 position is critical for
cytotoxicity. When the C3 moiety contains an electron-rich heterocycle,
the resulting BZDs have sub-micromolar potency and are selective for
T-cells. Cell death is consistent with apoptosis and does not result
from inhibition of the mitochondrial F(o)F1-ATPase, which is the
molecular target of recently reported cytotoxic 1,4-benzodiazepines.
Collectively, these studies begin to characterize some of the
structural elements required for the activity of a novel family of
T-cell-selective lymphotoxic agents.
PMID: 16488147
-----------------------------------------------------------------------------
If this turns off the cells gone WILD and leaves everything else alone
it
may be the next BIG thing for P.
randall.... Kill my wild cells! Don't know if i'm ready. Are they? You?
randall
P news from around the world.
First stop-- Boston.
Got Funky Nails?
http://cbs4boston.com/health/local_story_188153836.html
(CBS4) BOSTON Your fingernails can tell you a lot about your health.
You can find signs of illness right on your hands.
When Dorothy Russell looked closely at her nails, something didn't look
right. She noticed lines running across her finger and toe nails. "I
got scared because they said it could be melanoma cancer so that's the
reason I came here."
Meghan McEntee also noticed changes in her nails. They started to get
small cracks. "I just figured it would grow out but it's been a while
and it hasn't grown out as my nail grows."
>From heart disease to lung disease, diabetes to hepatitis, even vitamin
deficiencies, your nails -- just like your eyes -- can reveal valuable
clues about your overall health.
"The nails are a window to the physiology," said Dr. Ted Daly.
White nails can be early signs of liver disease. Dark lines can suggest
melanoma. Small red lines can indicate an infected heart valve and half
white, half-pink nails can suggest kidney disease.
"If you have any pigmentary discoloration, it's dark or its change in
color," said Daly.
Those are reasons to get to your doctor.
Since nails grow out of the cells that form the outer layer of skin,
they retain a history of everything that takes place in your body.
Dorothy didn't have melanoma, but her dermatologist discovered she had
another disease, melanonychia, which can indicate the onset of
Addison's disease.
Meghan is now taking a cream for psoriasis.
(randall note:: http://dermatology.about.com/library/bldeflongmel.htm
& http://dermatology.about.com/cs/nailanatomy/l/bldefsubungualm.htm )
--------------------------------------------
>From Nigeria today. Fashion tiPs for men. (not a scam)
http://www.thetidenews.com/article.aspx?qrDate=07/08/2006&qrTitle=Fashion%20tips%20for%20men&qrColumn=FASHION
[...]
Vertical patterns make you look taller and thinner.
Trouser cuffs make short legs look shorter.
Mixing it up
Combine your casual and dressy clothing this rainy season. Remember,
layering in the rainy season helps you better regulate your body
temperature and cut down on perspiration. This can help ease the
irritation of psoriasis. <sniP>
(randall notes:: so, do the horizontal patterns make you look like a
zebra?
Don't wear a bulls eye target, it can draw hunters! )
------------------------------------
Does the city of Beijing China have Psoriasis?
http://news.xinhuanet.com/english/2006-07/08/content_4807681.htm
[...]
When graffiti was taking shape in the United States in the late 1960s
and early 1970s, walls in China were splattered with "big-character
posters" and giant slogans. Both were bold and eye-catching. Both
vandalized numerous facades of public and private buildings. The
difference is, the Chinese graffitists, if they could be called that,
did not need to worry about being caught. They were busy denouncing
authorities and bullying the public, something their American
counterparts could only dream of.
Nowadays the most commonly seen graffiti on Chinese walls is the
type usually described by the local press as "psoriasis on the urban
landscape." They are small flyers - sometimes as tiny as a slip of
paper - pasted on electric poles, public phone booths and even
pavements. Every public space is their canvas.<sniP>
(randall note:: the last time this china city/psoriasis thing came up,
I figured it was
the 2008 olympics to blame as the trigger. )
-------------------------------------
Book review:: Pain Free for life
[...]
According to Brady, the underlying source of chronic pain can
frequently be traced to what he calls the Automatic Overload Syndrome,
which is the root cause of everything from psoriasis to insomnia, lower
back pain to irritable bowel syndrome. Brady goes on to explain how the
subconscious mind handles emotions, using repression to hide away
anger, fear, shame and other uncomfortable feelings that later cause
the body to react by manifesting pain symptoms. Categorizing personal
attitudes into five types, the author goes on to explore the importance
of spiritual health and provides a four page examine to determine the
reader's level of spiritual distress.
The basis of Brady's program lies in training the subconscious to
recognize that the source of pain is a mental manifestation and to
redirect the energy into more appropriate releases. Although plenty of
antidotal evidence backs up these claims and the occasional statistic
is mixed in, there have been no genuine scientific studies done to back
up the claims presented here. Still, for those living with chronic pain
this may be an option to look into as the placebo effect is well
documented and this program could provide a mental sugar pill to kick
start that effect. <sniP>
------------------------------------------------------------------
randall...
randall
P News from around the world.
Getting Pregnant and Psoriasis-- Diet?
I'ts a Miracle Baby!
http://www.voice-online.co.uk/content.php?show=9536
TARA'S STORY
After the failure of her ovulation-enhancing drugs, Tara Clinkscale
looked to the web to find alternatives, which is when she came across a
book called A New Dawn by Ian Stokes. She contacted Stokes and within
months she was pregnant.
[...]
Under Stokes's guidance, Tara started an eating programme that
removed certain foods. The results were dramatic. She lost 24 pounds,
her migraines stopped, skin problems she had for the last thirty years
cleared up, she began to ovulate naturally and witnessed a huge rise in
her progesterone. Within a few months Tara conceived and is due this
August. She has not experienced the massive weight gain that many
pregnant women experience and her doctor reports that the baby is very
healthy and advanced for its age.
[...]
INFERTILITY NOT A DISEASE
The science is compelling. Stokes argues that while our immune system
is programmed to protect the body from harm, it does so by attacking
bacteria and viruses using a vast array of chemicals that the body's
white blood cells manufacture.
He said: "Under normal circumstances, the attacks are brief and
violent - if such attacks are prolonged, the body can suffer damage
and cause inflammatory illnesses such as asthma, arthritis,
______-psoriasis_______ etc. But what is less well known, is that these
chemicals are also responsible for infertility and those conditions
that can have a devastating effect on fertility."
Stokes argues that the current approach to treating infertility misses
the point. "Infertility is not a disease but a sign of chronic
inflammation."
His answer for treating chronic inflammation is also simple. He says
that the chronic inflammation - itself caused by chronic immune
activation - can be triggered by anything that the body considers
'non-self'. The problem is, this non-self can be something as
simple as food, and therein lies the answer.
Following this logic, he refuses to classify his programme as
'treatment' for infertility. Instead, he describes it as "merely
the avoidance of cause... In real terms, there is no treatment as such,
simply the avoidance of a risk factor."
He said: "Food is normally converted from 'non-self' to
'self' by digestion but if digestion fails or the integrity of the
gut wall is compromised, food can enter the bloodstream in the form of
'non-self' and trigger an immune response.
"This is hugely complicated biochemistry but it is also the subject
of intense interest by researchers. However, very few recognise the
implications regarding food as an instigator and fertility as a
target."
At a time when the internet abounds with 'miracle' cures for
fertility problems - from black magic to hi-tech treatments that cost
thousands of pounds - Stokes's natural treatment is bound to
appeal.
Not everyone is convinced, though. Dr Geraldine Harshorne is an expert
in human fertility at the University of Warwick. She warns that it is
important to understand the scientific basis of any treatment.
"There are many reasons a particular person - male of female - is
infertile. It may be a physical cause such as blocked tubes, or it may
be due to a biochemical cause or a genetic cause.
"Now I certainly wouldn't rule out that some of those causes may be
helped by attention to good nutrition in various ways, but as far as a
nutrition-based treatment that's a different issue," she said.
<snip>
---------------------------------------
Diet isn't black magic baby!
Now that the fun part is over....
But what's fun with taking all the gluten out of your diet?
You know the first to go is white sugar and flour and and...
--------------------------
ScePtics enter- stage left.
Author Ian Stokes (a new dawn) has raised brows here,
http://www.aclearvoice.org/archives/2005/07/a_new_dawn_or_a.php
&
http://www.epc-odx.com/a-new-dawn/review.htm
__________________________________________
>From Pakistan today,
Religion, rape and psoriasis,
http://www.bosnewslife.com/news/2238-raped-pakistan-christian-fears-for-her-life
&
Aloe,
http://www2.ljworld.com/news/2006/jul/09/aloe_plant_can_rub_you_right_way/?living
&
Putting your psoriasis on Zanax,
http://www.medindia.net/news/view_news_main.asp?x=12157
Back to Pak for the med diet to less inflammation,
http://paktribune.com/news/index.php?id=149189
Got cancer? Here's a honey of a deal from New Zealand,
http://www.stuff.co.nz/stuff/0,2106,3725748a11,00.html
Can Glutamate in food, hurt ot help the psoriatic?
http://www.tripmastermonkey.com/archives/lifestyle/june_07_2006_is_msg_really_bad_for_you_1.php
[...]
"Take a fresh anchovy, pack it in salt, let it ferment for 9 months,
and you get fish sauce. An umami bomb," says Bill Briwa, a chef
instructor at the Culinary Institute of America in Napa, California.
A free glutamate bomb, too, we'd add. <sniP>
Now i'm craving the taste of Umami. Got anchovy fish sauce?
Uh, UH! This one has a fish coconut miso broth reciPe!
http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2006/07/06/WIG07JNG5A1.DTL
Miso want that last dish! A simPle squirt of Uma mi in my mouth isn't
gonna cut it now!
Must,
Find more,
http://www.napavalleyregister.com/articles/2006/06/08/features/food_and_w
ine/iq_3438927.txt
[...]
"umami is a savory taste imparted by glutamate and ribonucleotides,
including inosinate and guanylate, which occur naturally in many foods
including meat, fish, vegetables and dairy products. The taste of umami
itself is subtle. It blends well with other tastes to expand and round
out flavors. Most people don't recognize umami when they encounter it,
but it can be detected when eating ripe tomatoes, parmesan cheese,
cured ham, mushrooms, meat and fish. Umami plays an important role
making food taste delicious."
Hanni said that when there's considerable sweetness and umami taste in
food, it will exaggerate the bitterness, tannin and acidity in wine and
will suppress the sweetness and umami in wine. It will taste thinner
and have less of a natural taste.
Another Web site, worldwidewords.org, said taste is complicated, "...
the taste buds being helped along by sense of smell, by the feel of
substances in the mouth and even by the noise that food makes when we
chew it." And of umami, the site said, "It's sometimes associated with
a feeling of perfect quality in a taste, or of some special emotional
circumstance in which a taste is experienced. It is also said to
involve all the senses, not just that of taste." <snip>
Miso want this Uma mui experience.
Must get mind off of the experience!
Must find science to mute the efffects.
(randall morPhs in to CaPtain Kirk momentarilly)
Ok,
http://new.cbbqa.com/articles/Taste/ScienceOfTaste.html
Good. I'm back to normal, calcium ions show up for
P pathways as well.
But if your going to take out the inflammatory diet stuff, what
does one find to replace it with?
I can only wonder how our little mother, Tara Clink-scale is
doing dietetically? Eating omega-3's will help her
new born for breastfeeding.
Will the ClinkScales live happily ever after?
Beam me uP Scotty and leave the P off!
http://www.cartoonstock.com/newscartoons/cartoonists/bbr/lowres/bbrn37l.jpg
randall...good thing the sun trumps diet!
________________________________________________________________________
randall
Hey! Just re-read the last post. Besides being long
and loaded with tasty recePtor inducing foods it
was missing a few things.
Forgot to list these links. :(
This article has ideas to fix your gut and one product from Japan
(sold by Lonza, polarzinc) to heal the mucosal gut walls.
(keyword: lonza -for prior posts in the P ng)
If that Ian Stokes book, A New Dawn is correct, then this link has
the anwers to lower chronic inflammation and fix it faster when
you cheat eat.
After all old habits are hard to stoP eating.
http://www.naturalproductsinsider.com/articles/661feat01.html
Addressing Digestive Dysfunction
by Elizabeth Srejic
The human gut, equipped to handle the whole grain, fruit-, seed- and
vegetable-based eating pattern of our forebears, is adversely affected
by the low-fiber, high-fat diet of the contemporary, developed world.
As a result, digestive ailments are on the rise. Auspiciously,
supplementation with compounds designed to boost fiber intake, optimize
gut flora and quash inflammation may help to lower the incidence of
gastrointestinal problems.
It's dangerous to be an American gut. According to the Centers for
Disease Control (CDC),
[...]
Chelating the amino acid L-carnosine with zinc is another patented
treatment for its ability to support mucous secretion and exert
antioxidant effects. Research studies have referenced it by several
names, including Polaprezinc, Z-103, and Zinc L-carnosine; it is sold
in the United States by Lonza Inc. as PepZin GI®.
Research conducted at the Osaka Medical Center for Cancer and
Cardiovascular Diseases, Japan, investigated the impact of Polaprezinc
on H. pylori-induced gastritis in gerbils.9 After 12 weeks, the
researchers found supplementation had no influence on the H. pylori
density; however it attenuated the development of gastritis by
scavenging monochloramine, an important compound in the development of
gastric mucosal injury. Further research in H. pylori-inoculated
gerbils found Polaprezinc has the ability to inhibit gastric lesion
formation and reduce mucosal oxidative inflammation.10 Additional in
vitro studies suggest Polaprezinc enhanced mucosal growth factor
expression to heal lesions;11 and further protected the stomach against
NSAID-induced mucosal injury, probably through its antioxidative and
anti-inflammatory properties.12
In addition to nutrients and amino acids, several botanical compounds
may have antiulcer activity, including flavonoids, aloe and licorice.13
In vitro work has found aloe has anti-secretory activity on gastric
acid, and could thereby protect the gastric mucosa against infectious
agents.14 Another review on botanical compounds and gastric health
reported studies on garlic have found the plant to be effective against
common pathogenic bacteria, including H. pylori.15 And researchers from
the University of Illinois, Chicago, focused their attention on the
ability of gingerols, polyphenolic compounds isolated from ginger root
(Zingiber officinale), to inhibit the growth of H. pylori in vitro.16
They found a methanol extract of ginger rhizome inhibited the growth of
all 19 strains of H. pylori tested, concluding its activity against H.
pylori could also prevent development of gastric cancer.
<end>
References:
http://www.naturalproductsinsider.com/articles/661feat01refs.html
----------------------------------------------------
Should I send this to those sceptics in that last post?
By eating according to these ideas in this Liz Srejic article, your
gonna be fertile myrtle. :)
Will your psoriasis go south from less inflammation is the next
question.
randall... It always is!
randall
I've taken glucosamine, chondroitin, CoQ10, curcumin and a few other
things
out of my daily regimen. The basic program with sweet whey remains the
same.
I cleared recently. So, I started backing things out. While i've got a
few
spots and slow spreading, the sun is trumping anything major for now.
But i've got a BAD feeling for the next week. :(
The salient point about this trial, is i'm still eating an inflammatory
diet (for me anyway) but remain relatively unaffected while taking
IP-6.
This is of course in comparison to how i'd be doing without the
IP6 at all. Going cold turkey on all suPPLements and eating
the diet i've been on would be to hideous to even think about.
Sorta where the majority of you all are without your derms. LOL
Sorry, :(
But true. Now that i'm the master of my skin, I'm picking up tiPs like
crazy.
At least for another week i'll be taking ALCAR ( ala & alc), that I
started
around six weeks ago. I suspect synergism between, IP6, alcar and
glucosamine.
In the news recently for the big glucosamine.
-------------------------------------------------------------------------
Glucosamine seems to be anti-inflammatory. So, i'll find
current articles first.
http://www.medindia.net/news/view_news_main.asp?x=11909
When the issue of supplements arises, lines are drawn. On one side is
the scientific community, branding them all as useless. On the other
side is the general public, ignoring the experts and boosting sales
into the billions annually.
Why such extremes?
There are several reasons, but the crux of the matter is a lack of bona
fide evidence - the kind you need to convince the critics.
But doesn't lack of evidence mean lack of benefits? Not necessarily. It
could mean there has been no effort to prove or disprove effects. This
is the case for most supplements.
Why the lack of effort? Because you cannot patent supplements, which
are naturally occurring substances. No patent means no protection and
no incentive to invest millions proving or disproving the benefits.
Thankfully, things are beginning to change. The federal government has
recognized that supplements are extremely popular. Federal funds have
been made available to cover the cost of research.
Glucosamine and chondroitin are among the first supplements to be put
under the research microscope.
Glucosamine is touted as helping to rebuild articular cartilage - and
lost articular cartilage can lead to osteoarthritis. Chondroitin is
claimed to inhibit enzymes that tear down articular cartilage.
Thus, because of these complementary effects, the products typically
are packaged together as a means of reducing pain and inflammation and
regenerating articular cartilage.
Glucosamine is extracted from crab, lobster or shrimp shells.
Chondroitin comes from animal cartilage, mostly from sharks.
I have seen some miraculous effects of glucosamine and chondroitin.
Older folks who have given up vigorous activities like tennis have been
able to return to the court, moving about as if their joints were
decades younger.
These products had a great effect on my aging mother's mobility as they
eased the pain and inflammation in her worn-out knees. I've also
observed good effects on the joints of older animals.
However, there are many instances where there has been no effect. My
personal experience is mixed. There was a time when I felt a good
benefit, but now I don't. To be fair, the scale is balanced about
equally, pro and con.
Research results seem to be saying the same thing. A study in 2000 from
the Journal of the American Medical Association reported moderate to
large effects and concluded with cautious optimism that these
supplements may be helpful.
Other studies also published in reputable medical journals reported
similar upbeat but cautious findings.
In contrast, a large, comprehensive study (2006, New England Journal of
Medicine) reported essentially no benefits.
Then, another 2006 journal study concluded that the two supplements,
while not effective for those suffering from osteoarthritis in the
knees, were effective in patients with moderate to severe knee pain.
Overall, there's no clear message.
Another knock against supplements is lack of oversight by the Food and
Drug Administration. This means you have no way of knowing what is
really in the pills you buy. How pure is the product? What's the actual
dosage?
Consumer Reports examined the contents of 19 glucosamine and
chondroitin products and found that almost all of them contained what
they are supposed to according to their labels.
This is good news and removes this as a concern, assuming you purchase
from a well-established supplement company.
The bottom line
Because these products seem to work for some folks and not others, and
because research results are inconsistent, it's hard to make a blanket
recommendation.
Thus, I'll convey my standard advice regarding supplements: If you
think they may help, go for it. Shop for price and allow time to fully
judge effects.
Know that you likely will experience some degree of placebo (sugar
pill) effect. This means you will feel better because you believe you
should. But this tends to wear off pretty quickly, so give it time.
If they work for you, fine, keep using them. If they don't, you can
either quit or change to a different brand and try again until you are
convinced one way or the other.
Side effects appear to be minimal, with the potential for increased
gastrointestinal gas and softened stools.
Because supplements can interfere with prescription drugs, it's
important to inform your doctor if you make the choice to proceed.
A final word: For those, like my mother, who despise swallowing pills,
a new liquid supplement is coming out soon. It contains glucosamine,
chondroitin and other products in a drink made from fruit juice.
The product, called Elations, is being test-marketed in Louisville this
month.
========================================================
http://www.jacksonsun.com/apps/pbcs.dll/article?AID=/20060710/LIFESTYLE/607100302/1024
Glucosamine, a substance used in treating arthritis was now found to
play a role in reversing the aging symptoms, treating UV damaged skin
and preventing the formation of new age spots in women.
A team of dermatologists from Harvard Medical School have reported that
the more stable n-acetyl glucosamine have shown to reduce the melanin
content of skin cells thus proved its effect in UV-related skin damage
treatment.
For many women, accumulated sun exposure has already permanently
damaged their skin cells, causing them to overproduce pigment that
shows up as unsightly dark splotches and uneven skin tone over time.
But new research indicates that glucosamine - a compound best known for
treating arthritis - can actually help stop the formation of new age
spots, and help fade existing ones.
'These findings on glucosamine may impact the way dermatologists
treat UV-related skin damage in the future. Right now we have
prescription and surgical options, which some people aren't willing to
try,' says Alexa Kimball, M.D., assistant professor of dermatology,
Harvard Medical School and lead researcher on one of the studies
testing glucosamine. 'It's exciting to see this level of research
being done on topical cosmetic applications of glucosamine, and the
promising results.'
<sniP>
--------------------------------------------------------
--------------------------------------------------
And looking at pubmed for any abstracts. That one author said the gov
only recently was doling out the dough to study glucosamine.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16822580
Hyaluronan fragments: An information-rich system.
Stern R, Asari AA, Sugahara KN.
Department of Pathology and UCSF Comprehensive Cancer Center, School of
Medicine, University of California San Francisco, 513 Parnassus Avenue,
S-564, San Francisco, CA 94143-0511, USA.
Hyaluronan is a straight chain, glycosaminoglycan polymer of the
extracellular matrix composed of repeating units of the disaccharide
[-d-glucuronic acid-beta1,3-N-acetyl-d-glucosamine-beta1,4-](n).
Hyaluronan is synthesized in mammals by at least three synthases with
products of varying chain lengths. It has an extraordinary high rate of
turnover with polymers being funneled through three catabolic pathways.
At the cellular level, it is degraded progressively by a series of
enzymatic reactions that generate polymers of decreasing sizes. Despite
their exceedingly simple primary structure, hyaluronan fragments have
extraordinarily wide-ranging and often opposing biological functions.
There are large hyaluronan polymers that are space-filling,
anti-angiogenic, immunosuppressive, and that impede differentiation,
possibly by suppressing cell-cell interactions, or ligand access to
cell surface receptors. Hyaluronan chains, which can reach 2x10(4)kDa
in size, are involved in ovulation, embryogenesis, protection of
epithelial layer integrity, wound repair, and regeneration. Smaller
polysaccharide fragments are inflammatory, immuno-stimulatory and
angiogenic. They can also compete with larger hyaluronan polymers for
receptors. Low-molecular-size polymers appear to function as endogenous
"danger signals", while even smaller fragments can ameliorate these
effects. Tetrasaccharides, for example, are anti-apoptotic and inducers
of heat shock proteins. Various fragments trigger different signal
transduction pathways. Particular hyaluronan polysaccharides are also
generated by malignant cells in order to co-opt normal cellular
functions. How the small hyaluronan fragments are generated is unknown,
nor is it established whether the enzymes of hyaluronan synthesis and
degradation are involved in maintaining proper polymer sizes and
concentration. The vast range of activities of hyaluronan polymers is
reviewed here, in order to determine if patterns can be detected that
would provide insight into their production and regulation.
PMID: 16822580
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16822504
Glucosamine sulfate inhibits leukocyte adhesion in response to cytokine
stimulation of retinal pigment epithelial cells in vitro.
Chen JT, Chen PL, Chang YH, Chien MW, Chen YH, Lu DW.
Department of Ophthalmology, Tri-Service General Hospital, National
Defense Medical Center, 325, section 2, Cheng-Kung Road, Taipei 114,
Taiwan.
Glucosamine is an amine-containing sugar that exhibits
immunosuppressive effects in vitro and in vivo, although its mechanism
of action is unknown. We investigated whether glucosamine sulfate (GS)
modulates the proinflammatory cytokine interleukin (IL)-1beta-induced
expression and production of intercellular adhesion molecule (ICAM)-1,
the mechanism responsible for this effect, and whether GS inhibits
leukocyte adhesion to the monolayer of retinal pigment epithelial (RPE)
cells stimulated with various cytokines. We used flow cytometry and an
ARPE-19 cell model to determine the effect of GS on the production of
ICAM-1 in response to IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha
plus IL-1beta, TNF-alpha plus IL-6, and TNF-alpha plus interferon
(IFN)-gamma. We also used semiquantitative RT-PCR to determine the
effect of GS on IL-1beta-induced expression of the ICAM-1 gene, and
immunocytochemistry and western blotting to measure the effect of GS on
the activation and nuclear translocation of the nuclear factor
NF-kappaB and the degradation of cytoplasmic IkappaB. The functionality
of GS-modulated ICAM-1 on leukocyte adhesion was demonstrated in an RPE
cell-neutrophil adherence assay. IL-1beta increased the expression of
ICAM-1 at the mRNA and protein levels in ARPE-19 cells. GS
downregulated the production of ICAM-1 induced by IL-1beta, IL-6,
TNF-alpha, and IFN-gamma at the protein level in a dose-dependent
manner. GS also inhibited the nuclear translocation of NF-kappaB
subunit p65 and partially prevented the degradation of cytoplasmic
IkappaB in IL-1beta-stimulated ARPE-19 cells. GS significantly
decreased the number of neutrophils adhering to the RPE monolayer in
response to cytokines IL-1beta, IL-6, TNF-alpha, and IFN-gamma. GS
inhibits the expression of the ICAM-1 gene in ARPE-19 cells stimulated
with IL-1beta by blocking NF-kappaB subunit p65 translocation and by
partially preventing IkappaB degradation. GS also decreases leukocyte
adhesion to the monolayer of ARPE-19 cells stimulated with various
cytokines by decreasing ICAM-1 production. Our study demonstrates a
potentially important property of GS in reducing ICAM-1-mediated
inflammatory mechanisms in the eye.
PMID: 16822504
There are 28 abstracts for glucosamine posted in pubmed since June.
We're talking serious research. Who ever that guy is that said the gov
only recently was spending
$ on this must be wrong. This amount of research seems huge to me.
______________________________________
Back to me now.
If the sun doesn't live uP to it's clearing rePutation, i'll be going
back on glucosamine
and leaving the other things out to see how I do.
randall...as always my reports will be forthcoming. The clearer the
better!
randall
P news from around the world.
http://www.drugnewswire.com/3360/#
CAMBRIDGE, Mass., July 13 /PRNewswire/ -- Archemix Corp. announced
today a multi-year, multi-product alliance with Elan Corporation, plc
(NYSE:ELN) focused on the discovery, development, and commercialization
of first-in-class aptamer therapeutics to treat autoimmune disease. The
companies will seek to develop aptamer therapeutics to IL-23, a
cytokine that has emerged as a mediator in the chronic autoimmune
inflammatory diseases, and additional protein targets. The
collaboration combines Archemix's extensive expertise in aptamer
therapeutics with Elan's experience and leadership in the development
and commercialization of new therapies for autoimmune diseases.
[...]
About Interleukin 23
Interleukin 23, or IL-23, is a cytokine that has emerged as a mediator
in chronic autoimmune inflammatory diseases such as Multiple Sclerosis,
Crohn's Disease, Psoriasis, and Rheumatoid Arthritis. Preclinical
results have demonstrated that IL-23 exerts its pro-inflammatory
effects principally at the site of inflammation. It is hypothesized
that specific blockade of IL-23 may control clinical symptoms at the
level of the inflamed tissue without generally suppressing the
patient's immune system, thus preserving the body's ability to fight
infection. The current anti-cytokine treatments for autoimmune
disorders have a number of disadvantages, including an increased risk
of infection, increased chances of developing lymphoma, renal toxicity,
and limited efficacy. Archemix's aptamers are first-in-class
therapeutics for autoimmune diseases that exert their action by
specifically inhibiting IL-23 in the target tissue.
About Aptamers
Aptamers are single-stranded nucleic acids that form well-defined
three-dimensional shapes, allowing them to bind to target molecules in
a manner that is conceptually similar to antibodies. Aptamers combine
the optimal characteristics of small molecules and antibodies,
including high specificity and affinity, chemical and biological
stability, low immunogenicity, and the ability to target
protein-protein interactions. In contrast to monoclonal antibodies,
aptamers are chemically synthesized rather than biologically expressed,
potentially offering a significant cost advantage. As therapeutic
agents, aptamers have demonstrated clinical biological efficacy and
typically have excellent, tunable pharmacokinetic properties.
[...]
Further information on Archemix can be found at
http://www.archemix.com/.
------------------------------------------
A few aptamer abstracts is in order. Click the RA or pubmed the term
for 710 hits.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16815302
Aptamer selection based on inhibitory activity using an
evolution-mimicking algorithm.
Evolution on speed :)
---------------------------------------------
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16810258
Structure of the S-adenosylmethionine riboswitch regulatory mRNA
element.
Montange RK, Batey RT.
Riboswitches are cis-acting genetic regulatory elements found in the
5'-untranslated regions of messenger RNAs that control gene expression
through their ability to bind small molecule metabolites directly.
Regulation occurs through the interplay of two domains of the RNA: an
aptamer domain that responds to intracellular metabolite concentrations
and an expression platform that uses two mutually exclusive secondary
structures to direct a decision-making process. In Gram-positive
bacteria such as Bacillus species, riboswitches control the expression
of more than 2% of all genes through their ability to respond to a
diverse set of metabolites including amino acids, nucleobases and
protein cofactors. Here we report the 2.9-angstroms resolution crystal
structure of an S-adenosylmethionine (SAM)-responsive riboswitch from
Thermoanaerobacter tengcongensis complexed with S-adenosylmethionine,
an RNA element that controls the expression of several genes involved
in sulphur and methionine metabolism. This RNA folds into a complex
three-dimensional architecture that recognizes almost every functional
group of the ligand through a combination of direct and indirect
readout mechanisms. Ligand binding induces the formation of a series of
tertiary interactions with one of the helices, serving as a
communication link between the aptamer and expression platform domains.
PMID: 16810258
Could be a link here. Psoriatic liver become overburdened and stop
producing homeostatic levels of SAM-e throwing off STATS?
Taking some sam-e without anything else is a good test.
Let's check the group for a few terms,
http://groups.google.com/groups/search?q=riboswitches+psoriasis&qt_s=Search
&
http://groups.google.com/groups/search?q=S-adenosylmethionine+psoriasis&qt_s=Search
----------------------------------------------------------------------------------------
===========================================
Moving on to new PSORIASIS abstracts the last 24 hours.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16831294
Leukocyte infiltration and mRNA expression of IL-20, IL-8 and TNF-R P60
in psoriatic skin is driven by TNF-alpha.
Ogilvie AL, Luft M, Antoni C, Schuler G, Kalden JR, Lorenz HM.
Department of Dermatology, University Hospital of Erlangen-Nuremberg,
Erlangen, Germany.
Anti-TNF-alpha therapy with a chimeric monoclonal antibody (Infliximab,
Remicade) has been shown to be highly effective in the treatment of
skin lesions as well as arthritis in patients with psoriatic arthritis.
In this study we investigated the molecular consequences of the in vivo
TNF-alpha blockade with infliximab in psoriatic skin lesions of 6
patients with severe psoriatic arthritis. Biopsies from lesional and
non-lesional skin were taken before and 10 weeks after the initiation
of treatment. Immunohistochemistry and semiquantative RT-PCR were
performed focusing on proinflammatory gene products.
Immunohistochemistry, after three infusions, revealed a marked decrease
in the expression of TNF-alpha, HLA-DR, CD3, CD15, ICAM-1 and LFA-1
positive cells. By semiquantitative RT-PCR, we analysed mRNA expression
of IL-8, IL-20, TNF-R (TNF-R p60 and TNF-R p80), IL-1R I and IL-1R II,
as well as ICAM-2. Before therapy, m-RNA for IL-8, IL-20, TNF-R p60,
TNF-R p80, IL-1R II and ICAM-2 were detected in lesional skin. mRNA
expression of IL-8 and IL-20 completely disappeared and mRNA expression
of TNF-R p60 was reduced after therapy. This effect on IL-8 expression
was paralleled by a decreased infiltration of leukocytes in psoriatic
skin. These data suggest that the clinical response of anti-TNF-alpha
therapy in patients with psoriasis or psoriatic arthritis may be, at
least in part, caused by the inhibition of the production of
proinflammatory cytokines and by the decreased expression of adhesion
molecules with the consequence of an impaired migration of
proinflammatory cells into the inflamed tissue. These data further
support a critical role for TNF-alpha in the pathology of psoriasis.
PMID: 16831294
Those Mabs sure kick the craP outa TNF and thusly P.
Still leaves cause untended to. LPS-> TNF-> P severity
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16835316
Attractin, a dipeptidyl peptidase IV/CD26-like enzyme, is expressed on
human peripheral blood monocytes and potentially influences monocyte
function.
Wrenger S, Faust J, Friedrich D, Hoffmann T, Hartig R, Lendeckel U,
Kahne T, Thielitz A, Neubert K, Reinhold D.
Institutes of *Immunology and Experimental Internal Medicine and
Department of Dermatology and Venereology, Otto-von-Guericke-University
Magdeburg, Germany; Institute of Biochemistry, Department of
Biochemistry and Biotechnology, Martin-Luther University of
Halle-Wittenberg, Halle, Germany; and Probiodrug, Halle, Germany.
The ectoenzyme dipeptidyl peptidase IV (DP IV; CD26) was shown to play
a crucial role in T cell activation. Several compounds inhibiting DP
IV-like activity are currently under investigation for the treatment of
Type 2 diabetes, rheumatoid arthritis, colitis ulcerosa, psoriasis,
multiple sclerosis, and other diseases. In the present study, we show
that human peripheral blood monocytes express a DP IV-like enzyme
activity, which could be inhibited completely by the synthetic DP IV
inhibitor Lys[Z(NO2)]-thiazolidide. DP IV immunoreactivity was not
detectable on monocytes, and DP IV transcript levels of monocytes were
near the detection limit of quantitative polymerase chain reaction. It
is interesting that monocytes exhibit a strong mRNA expression of the
multifunctional DP IV-like ectoenzyme attractin and were highly
positive for attractin in flow cytometric analysis. Fluorescence
microscopy clearly demonstrated that attractin is located on the cell
surface of monocytes. Attractin immunoprecipitates hydrolyzed
Gly-Pro-pNA, indicating that monocyte-expressed attractin possesses DP
IV-like activity. Inhibitor kinetic studies with purified human plasma
attractin revealed that Lys[Z(NO2)]-thiazolidide not only inhibits DP
IV but also attractin (50% inhibition concentration=8.45x10(-9) M).
Studying the influence of this inhibitor on monocyte functions, we
observed a clear reduction of cell adhesion to fibronectin-coated
culture plates in the presence of Lys[Z(NO2)]-thiazolidide. Moreover,
this inhibitor significantly modulates the production of interleukin-1
(IL-1) receptor antagonist, IL-6, and transforming growth factor-beta1
in lipopolysaccharide-stimulated monocyte cultures. In summary, here,
we demonstrate for the first time expression of attractin on monocytes
and provide first, data suggesting that drugs directed to DP IV-like
enzyme activity could affect monocyte function via attractin
inhibition.
PMID: 16835316
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16831928
Autoimmunity and Bone
Focal erosions of cartilage and bone, which occur in the joints of
patients with autoimmune inflammatory arthritis (i.e., rheumatoid
arthritis (RA) and psoriatic arthritis [PsA]), represent the most
debilitating and irreversible components of the disease. Over the last
decade, seminal breakthroughs in our understanding of the cells and
signal transduction pathways central to this process have been
elucidated.
[...]
Here we propose the hypothesis that systemic TNF induces osteoclastic
differentiation of PBMC in PsA patients that correlates with their
erosive disease, and that the innate immune TNF/IFN axis in patients
with autoimmune disease dictates their erosive phenotype. To
demonstrate this, we injected wild-type C57B/6 and TNF-Tg mice with
poly I:C, which is known to induce systemic IFN responses, and show its
dominant effects on increasing the number of circulating
CD11b(+)/CD11c(+) precursor dendritic cells (pDC), concomitant with a
dramatic reduction in CD11b(+)/CD11c(-) OCP. Thus, systemic factors
produced by autoimmunity have a dramatic impact on active myelopoiesis
and bone homeostasis.
PMID: 16831928
Finding Nemo! WhooPs. I mean P genes.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16830340
A sliding-window weighted linkage disequilibrium test.
[...]
Analyses of two authentic data sets for psoriasis and Alzheimer's
disease using our proposed method confirmed previous findings. Genet.
Epidemiol. 2006. (c) 2006 Wiley-Liss, Inc.
PMID: 16830340
----------------------------------------------------------------------------
======================================
The last few weeks have been working back towards aerobic bacteria and
fungi
from the ground level uP.
So, lets review the gut for clues again. You know I consider it ground
zero.
The lamina propria and LPS are always on my radar. (keywords:: Tlr-4,
pamp cd14)
Lamina propria cells lack the TLR4 receptor, which recognizes the
common bacterial molecule LPS.
Finding a hidden gem in current abstracts is a good distraction. :)
A dynamic partnership: Celebrating our gut flora.
Sears CL.
Divisions of Infectious Diseases and Gastroenterology, Department of
Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
21205, USA.
Emerging data indicate that humans enjoy health through a productive
collaboration with their colonizing flora, the majority of whom reside
in the colon. This minireview provides a perspective on recent data and
the exciting scientific challenges ahead.
PMID: 16701579
The gut flora as a forgotten organ.
O'hara AM, Shanahan F.
Alimentary Pharmabiotic Centre, University College Cork, National
University of Ireland, Cork, Ireland.
The intestinal microflora is a positive health asset that crucially
influences the normal structural and functional development of the
mucosal immune system. Mucosal immune responses to resident intestinal
microflora require precise control and an immunosensory capacity for
distinguishing commensal from pathogenic bacteria. In genetically
susceptible individuals, some components of the flora can become a
liability and contribute to the pathogenesis of various intestinal
disorders, including inflammatory bowel diseases. It follows that
manipulation of the flora to enhance the beneficial components
represents a promising therapeutic strategy. The flora has a collective
metabolic activity equal to a virtual organ within an organ, and the
mechanisms underlying the conditioning influence of the bacteria on
mucosal homeostasis and immune responses are beginning to be
unravelled. An improved understanding of this hidden organ will reveal
secrets that are relevant to human health and to several infectious,
inflammatory and neoplastic disease processes.
PMID: 16819463
Sounds good. Seems like i'm a light year ahead of them. :)
Who knew you could do a rectal implant (wit kit) and eat a baby food
type of
diet without meat/booze/etc and take sweet whey and simply/easily
regrow colon flora beneficial to living symbiotically with MOTHER
nature?
I didn't till I did it! ;~)
Enteric flora in health and disease.
Guarner F.
Digestive System Research Unit, University Hospital Vall d'Hebron,
Barcelona, Spain. fgua...@medynet.com
The human gut is the natural habitat for a large and dynamic bacterial
community. Recently developed molecular biology tools suggest that a
substantial part of these bacterial populations are still to be
described. However, the relevance and impact of resident bacteria on
host's physiology and pathology is well documented. Major functions of
the gut microflora include metabolic activities that result in salvage
of energy and absorbable nutrients, protection of the colonized host
against invasion by alien microbes, and important trophic effects on
intestinal epithelia and on immune structure and function. Gut bacteria
play an essential role in the development and homeostasis of the immune
system. It is important to underscore that the specialised lymphoid
follicles of the gut mucosa are the major sites for induction and
regulation of the immune system. On the other hand, there is evidence
implicating the gut flora in certain pathological conditions, including
multisystem organ failure, colon cancer and inflammatory bowel
diseases. Copyright 2006 S. Karger AG, Basel.
PMID: 16498248
How does this sound? When P is triggered the gut goes with it and
that's why it's never fixed? Because the Gi tract isn't fixed?
Yeah! That and the P genes. ;~)
Ok wise guy, find the science now.
Gut motor function: immunological control in enteric infection and
inflammation.
Khan WI, Collins SM.
Intestinal Diseases Research Program, Division of Gastroenterology,
Department of Medicine, McMaster University, 1200 Main Street West,
Hamilton, Ontario, L8N 3Z5 Canada. kha...@mcmaster.ca
Alteration in gastrointestinal (GI) motility occurs in a variety of
clinical settings which include acute enteritis, inflammatory bowel
disease, intestinal pseudo-obstruction and irritable bowel syndrome
(IBS). Most disorders affecting the GI tract arise as a result of
noxious stimulation from the lumen via either microbes or chemicals.
However, it is not clear how injurious processes initiated in the
mucosa alter function in the deeper motor apparatus of the gut wall.
Activation of immune cells may lead to changes in motor-sensory
function in the gut resulting in the development of an efficient
defence force which assists in the eviction of the noxious agent from
the intestinal lumen. This review addresses the interface between
immune and motor system in the context of host resistance based on the
studies in murine model of enteric nematode parasite infection. These
studies clearly demonstrate that the infection-induced T helper 2 type
immune response is critical in producing the alterations of
infection-induced intestinal muscle function in this infection and that
this immune-mediated alteration in muscle function is associated with
host defence mechanisms. In addition, by manipulating the host immune
response, it is possible to modulate the accompanying muscle function,
and this may have clinical relevance. These observations not only
provide valuable information on the immunological control of gut motor
function and its role in host defence in enteric infection, but also
provide a basis for understanding pathophysiology of gastrointestinal
motility disorders such as in IBS.
PMID: 16487236
This one has to be off. P is Th1, not th2. So we need an explanation?
Got one?
Or we have to toss out the whole LPS thing in the gut? And go with
increased
tanslocation of endotoxin (lps) to explain the psoriatic Th1 skew,
without
any other gut explanations? Still need P genes. Lets go on.
Management of food allergy: vitamins, fatty acids or probiotics?
Laitinen K, Isolauri E.
Department of Paediatrics, University of Turku and Turku University
Central Hospital, Finland.
The dietary approach to allergic disease in infancy is evolving from
passive allergen avoidance to active stimulation of the immature immune
system, the aim of which is to support the establishment of tolerance.
This may include probiotics providing maturational signals for the
gut-associated lymphoid tissue and by balancing the generation of pro
and anti-inflammatory cytokines in addition to their capacity to reduce
the dietary antigen load by degrading and modifying macromolecules.
Probiotics have also been shown to reverse the increased intestinal
permeability characteristic of children with food allergy and to
enhance specific IgA responses frequently defective in children with
food allergy. The promotion of gut barrier functions by probiotics also
includes the normalization of the gut microecology, alterations in
which have been demonstrated in allergic individuals. Dietary lipids,
especially long-chain polyunsaturated fatty acids, regulate immune
function and may modify the adherence of microbes in the mucosa thereby
contributing to host-microbe interactions. The properties of specific
dietary compounds in optimal combinations and the joint effects of
nutrients can be exploited in the development of specific prophylactic
and therapeutic interventions. To meet these targets, rigorous
scientific effort is required to elucidate how the food matrix and the
dietary content impacts on the complex cascade of interrelated
immunological mechanisms in food allergy.
PMID: 16292082
OK big deal. Take out all the so called allergy foods and that would be
anything with
arachidonic acids and bingo, all but the most severe will clear.
Lets find some more.
http://www.twliterary.com/ghuffnagle_newsweek_01.html
Gut Flora? Great!
Maintaining a balance of microorganisms can help strengthen your
overall health.
By Mary Carmichael
Jan. 16, 2006 issue - You may use antibacterial dish soap and wash your
hands every time you sneeze, but Jeffrey Gordon wants you to know that
you're crawling with germs. Gordon, the director of the Center for
Genome Sciences at Washington University in St. Louis, studies bacteria
and ancient forms of single-celled life called archaea -- and no matter
how clean you think you are, your gut would make him a pretty good
laboratory. It's oozing with 750 trillion bacteria and archaea, and
there's very little you can do about it.
Then again, you probably wouldn't want to do anything about it, because
those little guys are good for you. The microbes in your gut have genes
of their own, and, as scientists are now learning, those genes are
essential to the body's functioning. Gut flora help the immune system
ward off more-dangerous bugs; they break down nutrients; they may even
manipulate how the body stores fat. If doctors could control the flora,
they might be able to ward off disease with a completely new toolbox.
Meanwhile, maintaining a good balance of microorganisms through diet
turns out to be an easy way to strengthen your overall health.
To some degree, people already manipulate their own gut flora in their
everyday lives. "The gut is the central sensor for the outside world.
Everything that comes from outside ultimately is going to end up
there," says University of Michigan immunologist Gary Huffnagle. Some
of the gut flora breeze into the body through the nose, while others
take the more direct route to the colon, along with food.
Scientists have decoded only about 10 percent of the bacteria, but the
ones they know about are exceedingly important to health. Most
obviously, the gut flora help the body digest food it otherwise
couldn't. Like all organisms, they break down nutrients in order to
survive. Three years ago Mark Schell, a microbiologist at the
University of Georgia, found that Bifido-bacterium longum has several
hundred genes for breaking apart sugars found in many common human
foods, including breast milk. Without the gut flora, those sugars would
pass through the human digestive tract; with the flora's help, humans
can reap calories and ener-gy from them. The gut flora also interact
with the immune system, "teaching" it not to overreact to intruders
that should be harmless, like allergens. So-called germ-free mice,
stripped of their gut flora, are vulnerable to outside infections and
react badly to potential allergens that don't cause problems in regular
mice. Once their gut flora are restored by researchers, their tolerance
returns.
Our own culture may promote unhealthiness. Gordon has argued that the
fast-food-heavy Western diet predisposes people to obesity by promoting
some gut microorganisms over others. Schell's studies have suggested
that a veggie-heavy diet is linked with high levels of B. longum, which
breaks down plant materials, while diets heavy on meat might suppress
the bacterium. Some foods that encourage gut-flora growth -- fiber,
fruit and veggie skins, some spices and herbs -- are now rare in many
people's daily diets. Overuse of antibiotics may also be destroying gut
flora.
Luckily, there are several ways to restore the microbial balance.
Lately, docs have been taking an interest in probiotic supplements,
which may help control infections. In a recent German study, subjects
taking three probiotics found that their colds were shorter and less
severe. Probiotics may even help ward off some of the most dangerous
germs, like Clostridium difficile, a nasty bug that sometimes infects
the colon after hospital patients are given strong antibiotics. To ward
off Clostridium, some docs are experimentally dosing their patients
with gut flora. Probiotic supplements are becoming more common in
health-food stores, too. Some may not contain enough of the bacteria to
lodge permanently in the body, so choose one that provides at least a
billion colony-forming units per serving. The most natural option?
Doctors often tell patients to eat yogurt after a course of
anti-biotics because fermented foods promote growth of Lactobacillus
and Bifidobacterium, the most fully studied beneficial bacteria. And
remember: getting enough fiber, fruits and vegetables is good for your
flora -- and your entire body.
(randall note:: iirc- i've posted huffnagle before. I must like the
guy)
------------------------------
Articles related to the toPic,
http://news.surfwax.com/chemistry/files/Archaea.html
---------------------------
http://www.msnbc.msn.com/id/10313003/site/newsweek/
[...]
Boosting the innate immune system, of course, has risks, chief among
them the possibility that doctors might overdo it. "The inflammatory
system is a two-edged sword," says Alderam. "It's there for a
reason-you absolutely need it to fight infection-but too much of it
is really, really bad." Doctors already know what happens when the
immune system is overactivated: the patient gets an autoimmune disease.
Some of the mechanisms the innate immune system uses to fight
pathogens-particularly inflammation-are responsible for a host of
health problems of their own. "There's definitely a potential
downside," says Krieg. He has seen it firsthand: some of the
participants in his trials have reacted badly, developing flulike
symptoms and inflammation or blistering at the site of the injection.
Of course, "controlling" the immune system means being able to turn it
down, as well as up. If autoimmune diseases result from an overactive
system, the thinking goes, why not just reverse the direction of the
system? In lupus, for instance, the body essentially turns on itself,
making antibodies to its own RNA or DNA. Or take allergies, in which
the immune system mistakes everyday substances for pathogens. If
doctors could use the innate system to stop the body from reacting in
those cases, they could essentially eliminate the illnesses. The
treatment would come with its own risk: turning the immune system down
too much. "You'd expect people to become a little more susceptible to
infections in those cases," says Alderam. Doctors would then have to
treat those infections with antibiotics. And they'd be happy to get far
enough down the road to face that problem.
-----------------------------------
H'mmm. Who is this person? I think I like the whey they think.
http://www.ideafestival.com/dynamic/speakers/Show_Bio.cfm?ID=14404
Mary Carmichael is a science journalist, a contributing writer at
Newsweek, and the books and web editor of Mental Floss. She has also
worked as a producer of the national public radio show "The Infinite
Mind," an associate producer for Frontline, and an editor for Newsweek,
for whom she wrote the 2004 cover story "The Quest for Memory Drugs"
(the basis for her upcoming book), the Newsweek Japan cover story
"Animal Emotions," and many more articles on science and health. She
also reported from Ground Zero on 9/11. She has contributed chapters to
two other books and written for the Boston Globe Sunday magazine and
the Washington Post. Her education includes a B.A. from Duke
University, graduate work in psychology and anthropology at Columbia
University, and fellowships with the Woods Hole Oceanographic
Institution and the Weidenbaum Center on the Economy, Government, and
Public Policy.
Ok.. mental floss.. infinite mind. seen ground zero.
Fix the gut, been a hero.
------------------------
Let's do the gut trip with all of the above and find my pet culprit,
LPS.
Here's a good hit. Has baby feeding (uwe link?) and LPS. Stick that in
the gut
and we have the Th2 response in the above abstract. Then at some
point a trigger comes along and we fliP floP into the Th1 psoriasis
I.M.I.D.
But what does it? Simple strep B? As in Mikhail's theory? And mine!
Wednesday, July 05, 2006
By David R. Blais & Illimar Altosaar
Four out of five people turn to plants to treat themselves when sick,
relying virtually exclusively on traditional herbal medicine for their
primary health care (1).
It is primarily in the more privileged and developed countries that
synthetic chemicals are supplementing the herbalists' apothecaries.
Still, a full quarter of prescription drugs are sourced directly from
plant seeds, roots, leaves, stalks, and exudates. Our food biochemistry
lab, established in 1978, has worked on the premise that by genetically
engineering plants already equipped with useful medical compounds it
may be possible to produce hard-to-get drugs. Hence, we have embarked
on a program to engineer plants that promote protection against
pathogens.
CD14 protecting mucosal surfaces
Plants and animals are constantly exposed to a multitude of
microorganisms that colonize their surfaces. In general, a symbiotic
relationship develops between the host and the microbe that provides
benefits and advantages to each organism. However, pathogenic
microorganisms often extend their colonizing capacities beyond mucosal
surfaces. These pathogenic invasions are initially countered by innate
defense mechanisms that preexist in the host and act within minutes
after the initial infection.
The innate immune response is based on an early recognition of
microbe-specific motifs, known as pathogen-associated molecular
patterns (PAMP). Most PAMPs are highly conserved surface-derived
molecules, such as lipopolysaccharide or LPS, a major component of the
outer membrane of Gram-negative bacteria. In mammals, this early
detection is mediated by pattern recognition receptors, such as CD14
(cluster of differentiation 14), capable of detecting picomolar
concentrations of LPS.
By binding to LPS, CD14 and the Toll-like receptor 4 (TLR4) complex
promote inflammatory responses at the site of infection through the
secretion of pro-inflammatory mediators and the recruitment of immune
cells. The ubiquitous presence of CD14 at mucosal surfaces and
secretions (i.e., tears, cornea, breast milk, saliva, lungs, intestine,
urine, sperm, and amniotic fluid) reflects its importance to the host
in fighting Gram-negative infections in these constantly challenged
mucosal environments (2,3).
Given its widespread mucosal distribution, numerous medical
applications have been suggested for CD14, such as reducing the
severity of LPS-induced septic shock and preventing Gram-negative
infections at mucosal surfaces (4). Despite several attempts in
different expression systems, recombinant human CD14 is still not mass
produced for clinical evaluation due to obstacles concerning expression
levels, production cost, as well as protein stability and activity
(reviewed in reference 5).
Plant-produced rhCD14 could prevent ocular infections
By targeting the expression of the human CD14 coding sequence in the
endosperm of tobacco seeds under the control of glutelin promoters, we
were able to obtain significant levels (16 µg rhCD14/g of seeds) of
recombinant human CD14 (rhCD14) proteins (5). Plant-produced rhCD14 was
efficiently stored in a stable and biologically active form in tobacco
seeds. When exposed to LPS from Pseudomonas aeruginosa, an ocular
Gram-negative pathogen, plant-produced rhCD14 was able to induce an
innate immune response of corneal epithelial cells similarly to CD14
naturally found in human tears (3,5).
These findings offer some promising applications for plant-made rhCD14
in preventing bacterial keratitis among contact lens users, and for use
during ocular interventions, such as laser eye surgery or suppressing
implant infections after orbital surgery (6). Such applications could
include the addition of rhCD14 to contact lens solutions or artificial
teardrops to mimic the immune advantages of human tears in reducing the
risk of developing ocular Gram-negative infections.
Plant-made rhCD14 for the fortification of infant milk formulas
Because the tobacco endosperm glycosylation of rhCD14 might affect its
stability and half-life, digestibility experiments were performed with
proteolytic enzymes to determine if plant-made rhCD14 had an increased
susceptibility to digestion. In vitro pepsin and pancreatin digestion,
to mimic the human newborn gastrointestinal tract, revealed that plant
rhCD14 has a proteolytic resistance similar to that of CD14 present in
human breast milk (2,5).
The slight variation between plant rhCD14 and breast milk CD14 proteins
might be attributed to the environmental milieu of the protein, such as
the presence of protease inhibitors in breast milk. With its similar
digestive susceptibility, rhCD14 produced in a food crop (or in a
non-food plant for confinement issues) could one day be added to
commercial infant milk formulas to mimic the immune advantage of breast
milk for the neonate and to creams for cracked nipples to prevent
mammary infections during lactation.
This latest potential application of 'humanizing' infant milk formula
with plant-produced breast milk proteins, such as rhCD14, might help
reduce mother-to-child transmission of HIV in resource-constrained
countries.7 No safe newborn feeding methods are currently available for
HIV-infected mothers in these countries since breast milk is a vehicle
of HIV transmission and infant formula is a source of gastrointestinal
illnesses due to the lack of breast milk protective immune factors and
unsanitary conditions during formula preparation. There is therefore an
urgent need to ensure that breast milk substitutes embody optimal
health benefits. To do so, transgenic food crops, such as rice (Fig.
1), could cheaply and safely reconstitute the beneficial and protective
breast milk proteome in infant formulas to replicate the immune
protection of breast milk against gastrointestinal illnesses while
keeping the HIV virus at bay (7).
At least seven breast milk proteins with immune properties have already
been produced in transgenic food crops (7). With our current knowledge
of the breast milk proteome and its fate in the newborn
gastrointestinal tract, along with the maturing plant biotechnology
sector, production of dozens more immune proteins in transgenic food
crops is deemed feasible to supplement such fortified formulas with
pharma flour.
Future perspectives
Plant-made rhCD14 was efficiently stored in a stable and biologically
active form in transgenic tobacco seeds. Transgenic rice, expressing
the codon-optimized version of the hCD14 coding sequence, along with
stronger promoters and signal sequences, such as the KDEL retention
signal, are currently being developed in our lab to further increase
the yields of the recombinant protein and allow direct oral delivery
(Fig. 1). This expression system constitutes a promising source of
rhCD14 to continue identifying the roles of this LPS receptor protein
in innate immune responses at mucosal surfaces in addition to the
aforementioned potential preventive and therapeutic medical
applications.
Sources
1. WHO. (2002) Traditional and alternative medicine. WHO Fact Sheet,
271: 1-3
2. Blais DR, Harrold J, Altosaar I. (2006) Killing the messenger in the
nick of time: persistence of breast milk sCD14 in the neonatal
gastrointestinal tract. Pediatr Res 59, 371-6
3. Blais DR, Vascotto SG, Griffith M, Altosaar I. (2005) LBP and CD14
secreted in tears by the lacrimal glands modulate the LPS response of
corneal epithelial cells. Invest Ophthalmol Vis Sci 46, 4235-44
4. Stelter F, Bernheiden M, Menzel R, et al. (1998) The molecular basis
for therapeutic concepts utilizing CD14. Prog Clin Biol Res 397, 301-13
5. Blais DR, Altosaar I. (2006) Human CD14 expressed in seeds of
transgenic tobacco displays similar proteolytic resistance and
bioactivity with its mammalian-produced counterpart. Transgenic Res 15,
151-64
6. Jordan DR, Brownstein S, Robinson J. (2006) Infected aluminum oxide
orbital implant. Ophthal Plast Reconstr Surg 22, 6-7
7. Blais DR, Altosaar I. (2006) Humanizing infant milk formula via
transgenic plants to decrease mother-to-child postnatal HIV
transmission. In preparation.
David R. Blais, Postdoc
David.Blais @nrc.ca
Illimar Altosaar, Professor
altosaar @uottawa.ca
Department of Biochemistry, Immunology and Microbiology
University of Ottawa
Ottawa, Ontario, Canada
Links:
* Source: Information Systems for Biotechnology
Related articles:
* Changing glucosinates for tailor-made, disease-resistant crops (19
May 2006)
* Gene mutation finding could help engineer resistance to crop
pathogens (23 Mar 2006)
* Survey results on plant-made vaccines discussed (03 Feb 2006)
* Engineering broad-spectrum disease resistance (06 Oct 2005)
___________________________________________________
Ok. Good clues.
Get the pubmed. Right.
Human CD14 expressed in seeds of transgenic tobacco displays similar
proteolytic resistance and bioactivity with its mammalian-produced
counterpart.
Blais DR, Altosaar I.
Department of Biochemistry, Microbiology and Immunology, University of
Ottawa, ON, Canada.
Human CD14 plays an important role in innate immunity by being the key
receptor of lipopolysaccharide found on Gram-negative bacteria. The
recently discovered widespread localization of CD14 in secretions and
mucosal surfaces reveals its extensive anti-microbial properties and
numerous potential medical applications. To produce active recombinant
human CD14 (rhCD14) for massive distribution, transgenic tobacco plants
were successfully generated to express rhCD14 in the seed endosperm
under the control of two versions (1.8 kb and 5.1 kb) of the rice
glutelin Gt-1 promoter. Plant-made rhCD14 proteins reached a
concentration of 16 microg/g of seeds and showed stability, proteolytic
resistance to pepsin digestion and ability to induce the release of
pro-inflammatory IL-6 and IL-8 cytokines in presence of LPS. The
expression of plant rhCD14 in tobacco seeds constitutes a promising
low-cost and abundant supply of this immune protein to further
investigate its roles in, impacts on and potential medical applications
for the innate immune system.
PMID: 16604457
------------------------------------
Perfect. Now get some psoriatic guts and start testing for LPS
translocation
and influence on tNF and IFN.
Find the p genes so we can end this craP!
randall... to much alcar makes for to long posts! LOL
randall
A new drug that may allow you to toss the needle away.
http://www.medadnews.com/News/index.cfm?articleid=357422
Roche Exercises Its Option Ipsen's GLP-1 Analogue BIM 51077 for Type
2 Diabetes
BASEL, Switzerland and PARIS, July 17, 2006--Roche and Actelion
announced today that they have entered into an exclusive worldwide
collaboration to jointly develop and commercialize Actelion's
selective S1P1 receptor agonist, an immunomodulator with the potential
for once-a-day oral dosing. The compound is currently being developed
in phase I. The two companies plan to jointly develop and commercialize
this novel compound for multiple autoimmune disorders.
"We are very pleased to partner with Actelion in this area where
there are still a number of high unmet medical needs and only few
treatment options are available," said Roche Chairman and CEO Franz
B. Humer. "This collaboration is a further step to strengthen our
emerging autoimmune disease franchise."
Jean-Paul Clozel, MD and Chief Executive Officer of Actelion commented:
"I am very proud about our collaboration with Roche, an excellent
partner to develop and promote multiple indications in parallel.
Together, we are well prepared to turn Actelion's scientific
breakthrough in selective S1P1 receptor agonists into a treatment that
has the potential to dramatically improve medical care for patients
with autoimmune disorders."
---------------------------------------------
There you go. Once a day oral or once a week needle?
What do you say?
Let's find some more info on this drug.
-----------------------------------------
http://www.actelion.com/uninet/www/www_main_p.nsf/Content/S1P1+Receptor+Agonist+in+Clinical+Development
S1P1 Receptor Agonist in Clinical Development
Sphingosine-1-phospate (S1P) is an endogenous phospholipid released by
platelets, mast and other cells. It is currently established that S1P
stimulates at least five different G-protein coupled receptors (GPCRs):
S1P1,2,3,4, and 5. Activation of these GPCRs mediates a complex variety
of biological responses, such as lymphocyte migration, endothelial cell
migration, blood vessel constriction, heart rate modulation and others.
It has been shown that S1P receptor modulators inhibit the egress and
recirculation of lymphocytes from lymph nodes, and this represents a
new therapeutic strategy for treating certain autoimmune disease
[...]
Actelion's efforts in the field of selective S1P1 receptor agonists
started in 1999 by focusing on receptors found on the endothelium, the
inner lining of blood vessels. The result of these research efforts is
Actelion's orally active, selective S1P1 receptor agonist. In
pre-clinical models, this compound, a novel, orally active
immunomodulator, has been shown to substantially decrease the number of
circulating lymphocytes and to prevent arthritis. The compound is
currently undergoing phase I safety and tolerability testing.
-----------------------------------------
& the abstract for this.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16319133&dopt=Abstract
Cell migration activated by platelet-derived growth factor receptor is
blocked by an inverse agonist of the sphingosine 1-phosphate
receptor-1.
Waters CM, Long J, Gorshkova I, Fujiwara Y, Connell M, Belmonte KE,
Tigyi G, Natarajan V, Pyne S, Pyne NJ.
Department of Physiology and Pharmacology, Strathclyde Institute for
Biomedical Sciences, University of Strathclyde, Glasgow, UK.
We have previously identified a novel complex between the
platelet-derived growth factor (PDGF)beta receptor and the sphingosine
1-phosphate receptor-1 (S1P1). The complex permits the utilization of
active G-protein subunits (made available by constitutively active S1P1
receptor) by the PDGFbeta receptor kinase to transmit signals to
p42/p44 MAPK in response to PDGF. Therefore, an inverse agonist of the
S1P1 receptor is predicted to reduce signal transduction from PDGFbeta
receptor tyrosine kinase by blocking the constitutive activity of the
G-protein coupled receptor. SB649146 is a novel inverse agonist of the
S1P1 receptor. First, SB649146 displaced the S1P1 receptor agonist
dihydrosphingosine 1-phosphate from membranes expressing the
recombinant S1P1 receptor. Second, SB649146 reduced basal recombinant
S1P1 receptor-induced GTPgammaS binding and S1P-induced GTPgammaS
binding in membranes. Third, SB649146 blocked the S1P-induced
activation of p42/p44 MAPK in airway smooth muscle cells, a response
that is mediated by the S1P1 receptor. We now report that inverse
agonism of the S1P1 receptor with SB649146 reduced the endocytosis of
the PDGFbeta receptor-S1P1 receptor complex and the stimulation of
p42/p44 MAPK and cell migration in response to PDGF. These findings are
the first to report that a GPCR inverse-agonist reduces growth
factor-induced receptor tyrosine kinase signaling, fundamentally
broadening their mechanism of action. The data obtained with SB649146
also suggest that the constitutively active endogenous S1P1 receptor
enhances PDGF-induced cell migration.
PMID: 16319133
randall
randall
P News from around the world.
http://www.marketwire.com/mw/release_html_b1?release_id=145069
CIMZIA(TM) Shows Promise in Treatment of Psoriasis
BRUSSELS, BELGIUM -- (MARKET WIRE) -- July 18, 2006 --
Significant positive results in 12-week phase II trial
BRUSSELS (Belgium), July 18, 2006 - 7:00 am CET - UCB today announced
significant positive results from the first study to evaluate the
efficacy and safety of CIMZIA™ (certolizumab pegol, CDP870), a new
type of anti-tumour necrosis factor (anti-TNF) therapy, in the
treatment of patients with moderate to severe psoriasis.
The phase II, randomized, double-blind, placebo-controlled dose-ranging
study involved 176 patients with moderate to severe chronic plaque
psoriasis who were candidates for systemic therapy and/or photo- or
photochemo-therapy. The patients were randomized to one of two
different subcutaneous dosing regimens using the liquid formulation:
CIMZIA™ 400mg given every other week, or an initial dose of CIMZIA™
400mg followed by a dose of CIMZIA™ 200mg given every other week; or
placebo.
The co-primary endpoints for the study were achieved with a high degree
of statistical significance, including the proportion of patients
achieving a 75% decrease from baseline in Psoriasis Area and Severity
Index score following treatment ('PASI 75') at week 12:
+-------------------------------------------------------------------------------------+
| | | |
|
| | Placebo |---- CIMZIA™ | CIMZIA™ |
| | | 200mg |
400mg |
|-----------------------------------+---------+------------+------------------------|
| | | | |
| Percentage of patients | 6.8 | 74.6 | 82.8 |
| achieving PASI 75 at week 12 | | (p < 0.001)| (p < 0.001)|
+----------------------------------------------------------------------------------------+
Results also suggest CIMZIA™ to be well-tolerated, with the level of
adverse events as expected for an anti-TNF.
"These initial results in psoriasis suggest that certolizumab pegol has
the potential to become a highly effective and well-tolerated addition
to the biologic treatment options currently available for this
difficult-to-treat disease," commented Professor Jean-Paul Ortonne,
Hôpital L'Archet, Nice, France and a lead investigator on the trial.
"We look forward to the results from further clinical trials confirming
these initial findings."
"The data from this first trial in psoriasis are highly encouraging,
revealing the tremendous potential for CIMZIA™ in the treatment of
moderate to severe psoriasis, building on the robust efficacy
demonstrated in the clinical trials in Crohn's disease, and further
reinforcing our commitment to the phase III programme in psoriasis,"
added Olav Hellebo, President of Inflammation Operations for UCB.
A 24-week follow-up period to this study is currently ongoing, with a
retreatment study also in progress. Data from the CIMZIA™ psoriasis
clinical trial programme will be presented at forthcoming dermatology
congresses.
UCB submitted requests for regulatory approval for CIMZIA™ to the
U.S. (in February 2006) and European (in April 2006) regulatory
authorities for the treatment of Crohn's disease. In addition to the
current development programme in Crohn's disease, ongoing phase III
studies are investigating the efficacy and tolerability of CIMZIA™ in
the treatment of rheumatoid arthritis.
About CIMZIA™
CIMZIA™ is the first and only PEGylated Fab' fragment of a humanized
anti-TNF-alpha antibody (TNF; Tumour Necrosis Factor). The engineered
Fab' fragment retains the biologic potency of the original antibody.
CIMZIA™ has a high affinity for human TNF-alpha, selectively
neutralizing the pathophysiological effects of TNF-alpha. Over the past
decade, TNF-alpha has emerged as a major target of basic research and
clinical investigation. This cytokine plays a key role in mediating
pathological inflammation, and excess TNF-alpha production has been
directly implicated in a wide variety of diseases.
About Psoriasis
Psoriasis is a chronic skin disease of scaling and inflammation that
affects around 125 million people worldwide, including 2% of the
European population (one in 50 people). Although the disease occurs in
all age groups, it primarily affects adults. Psoriasis occurs when skin
cells quickly rise from their origin below the surface of the skin and
pile up on the surface before they have a chance to mature. Usually
this movement (also called turnover) takes about a month, but in
psoriasis it may occur in only a few days.
In its typical form, psoriasis results in patches of thick, red
(inflamed) skin covered with silvery scales. These patches, which are
sometimes referred to as plaques, usually itch or feel sore. They most
often occur on the elbows, knees, other parts of the legs, scalp, lower
back, face, palms, and soles of the feet, but they can occur on skin
anywhere on the body. The cause of psoriasis is unknown, but it is
thought to result from a deficiency in the body's immune system. There
is no 'cure' for the disease, which is characterised by outbreaks
interspersed by varying periods of remission. Psoriasis can have a
markedly negative effect on quality of life, affecting a sufferer's
physical, social, and psychological functioning.[1]
Psoriasis Assessment Tools in Clinical Trials
The 'Gold Standard' for the assessment of extensive psoriasis is the
Psoriasis Area and Severity Index (PASI). This measures the average
redness, thickness and scaliness of the lesions (each graded on a 0-4
scale), weighted by the area of involvement. PASI 75, a 75% improvement
in PASI, is well established as a clinically meaningful endpoint for
clinical trials.[2]
About UCB
UCB (www.ucb-group.com) is a leading global biopharmaceutical company
dedicated to the research, development and commercialization of
innovative pharmaceutical and biotechnology products in the fields of
central nervous system disorders, allergy/respiratory diseases, immune
and inflammatory disorders and oncology - UCB focuses on securing a
leading position in severe disease categories. Employing over 8,300
people in 40 countries, UCB achieved revenues of EUR 2.3 billion in
2005. UCB is listed on the Euronext Brussels Exchange. Worldwide
headquarters are located in Brussels, Belgium.
[...]
References
[1] National Psoriasis Foundation.
www.omni.ac.uk/browse/mesh/DO11565.html. Accessed 4 July 2006.
[2] Feldman SR, Krueger GG. Psoriasis assessment tools in clinical
trials. Annals of the Rheumatic Diseases 2005; 64: ii65-ii68.
--------------------------------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=47310&nfid=nl
Embryonic Mutation Of FGFR3 Gene Linked To Thickening Of The Skin
Approximately 1 in 1,000 people suffer from localized areas of
thickened skin called epidermal nevi. However, the genetic basis of
this condition has remained elusive, until now. In a study appearing
online on July 13 in advance of print publication in the August issue
of the Journal of Clinical Investigation, Christian Hafner and
colleagues from the University of Regensburg examined epidermal nevi
from 33 patients and found that in 33% of patients studied the
epidermal nevi were caused by mosaicism of activating mutations in the
human epidermis of the gene FGFR3 (fibroblast growth factor receptor
3). These appeared to result from mutations that occurred during
embryonic development of these individuals. Since molecular-targeted
inhibitors of FGFR3 are already available, topical treatment of the
sometimes very disfiguring epidermal nevi with these inhibitors may
represent a promising non-invasive therapeutic option, especially in
children.
TITLE: Mosaicism of activating FGFR3 mutations in human skin causes
epidermal nevi
AUTHOR CONTACT:
Christian Hafner
University of Regensburg, Regensburg, Germany.
E-mail: christian.hafner @klinik.uni-regensburg.de.
View the PDF of this article at:
http://https://www.the-jci.org/article.php?id=28163
--------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=47034&nfid=nl
Lumenis(R) Ltd., a global developer, manufacturer and seller of laser
and light-based devices for medical, aesthetic, ophthalmic, dental and
veterinary applications, announced today the launch of ActiveFX(TM), an
effective, single treatment procedure for skin rejuvenation. The
ActiveFX procedure can be used to treat fine lines, wrinkles, skin
laxity, discoloration (e.g., freckles, "age spots," etc.), and other
effects of aging and sun damage.
"Recent trends indicate younger and more active patients are
increasingly seeking skin rejuvenation procedures to treat photoaging
that is noticeable, though not yet severe. At the same time, they are
averse to procedures that require multiple visits or a lengthy
recovery. For these patients, efficacy and convenience are both
important -- they want clearly visible results quickly, but they don't
want a lot of 'downtime' after the treatment," commented Avner Raz,
Lumenis President and CEO.
[...]
The ActiveFX procedure works by applying the CO2 laser energy in a very
narrow, scanned beam. This results in the creation of very tiny columns
of thermal damage that penetrate deep down to the dermis and stimulate
the growth of new collagen. The energy is applied in a "fractional" way
-- that is, the tiny columns of thermal damage are spaced so that
tissue between each is spared -- which results in a faster healing
process. ActiveFX differs from other aesthetic procedures employing
fractional approaches because it uses CO2 laser energy, which is
considered by many the optimal treatment for photoaged and
environmentally damaged skin.
CO2 energy is the ideal because it treats the areas of discoloration
closer to the surface and also penetrates deep into the dermis,
eliminating damaged cells and stimulating the growth of new collagen.
This new collagen lifts and supports the skin's surface. For patients
desiring dramatic results and willing to accept downtime, traditional
CO2 resurfacing remains a very good option. However, for active
patients desiring significant effects from a single treatment with very
little downtime, the ActiveFX procedure provides an exciting
alternative.
The ActiveFX procedure is a unique, proprietary application of the
Lumenis UltraPulse(R) Encore(TM) system. This system uses CO2 laser
energy to perform ActiveFX and other skin rejuvenation procedures, as
well as various incisional and excisional dermatologic and surgical
procedures.
<sniP>
------------------------------------------------------
Knock that GERD right out of your guts.
http://www.medicalnewstoday.com/medicalnews.php?newsid=47023&nfid=nl
Procter & Gamble Pharmaceuticals, Inc., a division of The Procter &
Gamble Company (NYSE: PG) and ARYx Therapeutics, a private drug
discovery and development company, today announced a strategic alliance
under which P&G will develop and commercialize ARYx's novel drug,
ATI-7505, for the treatment of gastrointestinal disorders such as
gastroesophageal reflux disease (GERD) and gastroparesis (delayed
emptying of the stomach).
[...]
ATI-7505 is an oral, serotonin type 4 (5HT4) agonist that is in Phase 2
development. ATI-7505 has been shown to have prokinetic properties
(increases upper GI motility, which is believed to play a beneficial
role in GI symptom reduction). Based on its mechanism of action,
initial studies show that ATI- 7505 prevents the regurgitation of
stomach contents into the esophagus and accelerates the emptying of the
stomach. This action may help relieve the symptoms of conditions where
motility of the gastrointestinal tract is a problem. A prior 5HT4
agonist, Propulsid(R) (cisapride), achieved nearly $1 billion in global
sales, but was withdrawn from the market in 2000 due to side effects.
ATI-7505 was designed using ARYx technology to retain the identical
mechanism of action, while eliminating the safety issues. Clinical
trial results to date support this target product profile, but larger
studies are required to confirm the drug's efficacy and safety.
<sniP>
-----------------------------------------------------
Allergy
http://www.medicalnewstoday.com/medicalnews.php?newsid=47309&nfid=nl
The neonatal Fc receptor (FcRn) is involved in binding IgG and the
embryonic acquisition of IgG from the mother through absorption across
the lining of the intestine. Until now, the role that FcRn played in
the intestine beyond neonatal life has remained a mystery. In a study
in mice appearing online on July 13 in advance of print publication in
the August issue of the Journal of Clinical Investigation, Richard
Blumberg and colleagues at Harvard Medical School demonstrate for the
first time that FcRn, through it's ability to secrete IgG, provides
defense against infection by the gut bacterium Citrobacter rodentium.
Animals that lacked FcRn were sensitive to Citrobacter rodentium
infection. The ability to clear Citrobacter was associated with
significant enhancement of the adaptive immune response in regional
lymphoid organs. These data define the physiologic function of FcRn in
the intestinal epithelium as a means to provide host immune
surveillance against encounters with luminal and epithelial pathogens.
--------------------------------------------------------
Cranberries for your gums
http://www.medicalnewstoday.com/medicalnews.php?newsid=46874&nfid=nl
---------------------------------------------------
Neuropeptide to look like a hollywood star.
http://www.medicalnewstoday.com/medicalnews.php?newsid=47361&nfid=nl
Shionogi & Co, Ltd. today announced positive top-line efficacy results
from a Phase IIa proof-of-concept trial with S-2367, an internally
discovered drug candidate for obesity and related conditions. The
unique mechanism of action of S-2367 involves blocking receptor binding
of neuropeptide Y (NPY), a neurotransmitter involved in regulation of
energy balance and food consumption. NPY levels are particularly
elevated in reduced weight or food deprived subjects, resulting in
stimulation of food intake. S-2367 was designed to counteract elevated
NPY levels, thereby promoting weight loss and continued weight loss
maintenance. Shionogi assessed the safety and efficacy of S-2367
once-daily treatment on a population of 342 obese subjects across 20
sites in the United States. In summary, the study met its primary
endpoint and demonstrated a statistically significant effect in
maintaining and continuing weight loss in these obese subjects,
validating the concept and utility of S-2367. A full analysis of the
current study data, including secondary efficacy and metabolic
parameters is underway. <sniP>
-------------------------------------------------------
Capsaicin for pain relieve
http://www.medicalnewstoday.com/medicalnews.php?newsid=47315&nfid=nl
-----------------------------------------------
randall
P Podcasting
http://releases.usnewswire.com/GetRelease.asp?id=69507
Psoriasis Group Launches New Psoriasis Podcast Series with Look to
Future of Psoriasis Treatments
7/20/2006 7:30:00 AM
To: National Desk, Health Reporter
Contact: Michael Paranzino of Psoriasis Cure Now, 202-253-4863 or
mic...@psorcurenow.org; Web: http://www.psorcurenow.org
KENSINGTON, Md., July 20 /U.S. Newswire/ -- "Psoriasis Cure Now," a
nonprofit patient advocacy group, today unveiled the first in a new
series of podcasts that will discuss issues of interest to people with
psoriasis and/or psoriatic arthritis. These audio programs, which
include interviews with leaders in the fields of psoriasis treatment
and research, can be listened to on any computer and can also be
downloaded from Apple's iTunes website to be played on an iPod.
The first psoriasis podcast includes an interview with Steven R.
Feldman, MD, PhD, a professor of dermatology, pathology and public
health sciences at Wake Forest University School of Medicine and an
internationally recognized authority on psoriasis. Dr. Feldman's
interview focuses on the future of psoriasis treatment. The podcast
also includes an update on Psoriasis Cure Now's effort to convince
Google to stop running ads for phony miracle "cures" for psoriasis, and
the program closes with an excerpt from a new song called "Psoriatic"
by eccentric cult icon Scott Walker. These free podcasts are available
at http://www.psorcurenow.org/podcasts.php .
"Podcasts are a wonderful vehicle to reach targeted audiences with
important health information," said Michael Paranzino, president of
Psoriasis Cure Now, "and these audio programs will allow us to reach
psoriasis patients and their families to help them find more effective
treatments and better understand this challenging disease."
Psoriasis is an incurable, non-contagious disease of the immune system
that can first strike at any age, causing painful skin lesions, and
often, arthritic symptoms. A 1999 study found that psoriasis causes
reductions in physical and mental functioning comparable to that seen
in diabetes, heart disease, hypertension, depression and other
diseases. As many as 7.5 million Americans have psoriasis.
"There are more than 60 versions of the Hokey Pokey available on iTunes
-- admittedly, a music classic -- but until now, psoriasis has been
absent from the service," Paranzino added. "We think music and health
information can coexist in this versatile format, and we're grateful
that someone of Dr. Feldman's stature was willing to share with us his
compelling insights about the future of psoriasis treatments. People
with psoriasis and others interested in the disease will draw
inspiration from his remarks."
New psoriasis podcasts will be added monthly. The podcasts are made
possible by an unrestricted educational grant from Genentech, as well
as by individual contributions from psoriasis patients and their loved
ones.
----------------------------------------------------------------
randall
randall
P news from around the world.
>From the UK.
http://news.bbc.co.uk/1/hi/magazine/5194394.stm
In your face
In a world obsessed by looks, those living with facial disfigurements
often find things a struggle. But they are now learning they can be
different and be happy.
At just eight years old Beverley Fulker started wearing thick, greasy
foundation to hide the port wine stain birthmark on her face.
"My face looked as if it were covered in mud because of the amount of
make-up I put on. It looked awful but I didn't think I had any other
option, it was still better than showing my birthmark."
She continued to camouflage it for a further 28 years, until two years
ago. Now she has set up a website called Love Your Mark to encourage
others to embrace their birthmarks as part of who they are and start
feeling better about themselves.
People from around the world started contacting her through the site
and she soon realised that those with prominent birthmarks experience
the same problems. She also realised there was no one saying it was OK
to be yourself, to embrace your mark instead of hiding it.
"As a child, I would have been ecstatic if I had been able to meet
others with birthmarks," says Beverley, from Leigh-on-Sea in Essex. "I
want to make it easier for children and adults to face the world.
Often the biggest problems people with birthmarks experience are
psychological. They can have low self-esteem and be cripplingly shy.
Top psychologist Dr Linda Papadopoulos, who has studied and written
books on body image, says what Beverley is doing is hugely important
and positive, especially in an era when everything is distilled down to
being thin and beautiful.
"Very little of a woman's worth is measured by anything but how she
looks," she says. "This minimises a woman to just what the size of
their bums and boobs are.
"When I studied facial disfigurements I thought there would be a
correlation between the size of a disfigurement and how affected people
were by it, but it doesn't work that way. People with the smallest mark
can be hugely traumatised.
"It is all about how you choose to see yourself, which is why this
website is so important. To be happy people need to change the way they
think of themselves, rather than sit there waiting for a new laser to
be invented that will totally remove a birthmark."
Plastic surgery
Problems often start at a young age, when people become aware they are
different. Treatment can include laser surgery, injections or drugs,
but success depends on the individual. Some birthmarks can never be
removed.
[...]
[reader's comments]
Good luck to these ladies. I have psoriasis on both my legs and
complete strangers march over demanding to know what is wrong with me.
I tell them its ringworm and highly contagious - they usually disappear
very rapidly. I'm more embarrassed among people I know, so I only go
bare-legged at home or where I'm not known. I've had this since I was
14 and I'm 41 now, but it doesn't get any easier to live with.
Helen, Manchester
<sniP>
------------------------------------------------------------------
http://www.irishhealth.com/?level=4&id=9934
Skin conditions impair kids' lives
[Posted: Fri 21/07/2006]
Children and teenagers with serious skin conditions feel that their
quality of life is impaired almost to the same extent as those with
chronic conditions such as epilepsy and diabetes, the results of a new
study indicate.
A team of Scottish researchers surveyed 379 young people, aged five to
16, who had been suffering from skin diseases like acne, eczema and
psoriasis. All had the skin conditions for at least six months. Their
parents were also surveyed.
The survey looked at how much the condition impaired the child's
quality of life when it came to factors such as pain, loss of sleep,
medical treatment, dietary restrictions, interference with school,
friendships and teasing or bullying.
The researchers also surveyed the parents of 161 children with chronic
conditions and then compared the results.
According to the children who took part, psoriasis and eczema were the
two skin conditions that caused the greatest distress. Both were given
a 'quality of life impairment score' of 31%. They were followed by
urticaria (20%) and acne (18%).
>From the parents' prospective, eczema was the biggest skin problem
(33%), followed by urticaria (28%) and psoriasis (27%).
<sniP>
--------------------------------------------------------------------------
These folks need to find a forum, like this one. Or the NPF, PHO or
that
one in Michigan.
I'll find the the list.
NPF
http://www.psoriasis.org/forum/forumdisplay.php?f=16
to navigate to the forums use the forum tools box or
http://www.psoriasis.org/community/forum/
PHO, (psoriasis help org)
http://www.psoriasis-help.org.uk/community/
Mipsoriasis,
http://www.mipsoriasis.org/forum/index.php?
Skincell Forum
http://www.skincell.org/yabbse/index.php
from:: http://www.skincell.org/
Introduce yourself,
http://www.skincell.org/yabbse/index.php/board,1.0.html
LINKS and things,
http://pso.webwillow.com/links.html
from
http://pso.webwillow.com/
Eds place,
http://www.flakehq.com/o-places.htm
The other ED's place (Anderson)
http://www.pinch.com/skin/
Seach tools,
http://www.pinch.com/html/search.html
About the usenet (The psoriasis newsgroup comes to mind)
http://www.pinch.com/skin/p.html
Kim
http://www.psoriasisfaq.com/
------------------------------------------------------------------------------
You can rant or read somewhere right now. :)
randall
randall
P News/ABstracts from Pubmed.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16858420&query_hl=4&itool=pubmed_docsum
Increased Expression of Wnt5a in Psoriatic Plaques.
* Reischl J,
* Schwenke S,
* Beekman JM,
* Mrowietz U,
* Sturzebecher S,
* Heubach JF.
1Schering AG Berlin, Global Pharmacogenomics, Biomarker Development and
Non-Clinical Statistics, Berlin, Germany.
Psoriasis vulgaris is characterized by hyperproliferation and
incomplete terminal differentiation of epidermal keratinocytes. Despite
the established role of Wnt pathways in the regulation of stem cell
proliferation and differentiation, they have not yet been associated
with the pathophysiology of psoriasis. Here, we took biopsies from
uninvolved and from lesional skin of 20 patients with plaque-type
psoriasis. The biopsies were used for microarray RNA expression
profiling. Based on paired samples from 13 patients, we defined 179
genes that were more than 2-fold differentially expressed in lesional
skin. This list included 16 genes with known or possible association to
the canonical Wnt/beta-catenin or the non-canonical Wnt/Ca(2+) pathway.
The expression of Wnt5a was 4-fold higher in lesional skin. Other Wnt
molecules were largely unchanged (Wnt4 and Wnt16), or tended to be
expressed at lower levels (Wnt7b). The mRNA expression levels of two
inhibitory factors related to Wnt signaling, frizzled-related protein,
and dickkopf homolog 2, were reduced in lesional skin, as was mRNA
expression of cyclin D1. These findings were confirmed by quantitative
reverse transcription-PCR experiments. We conclude that Wnt5a and other
Wnt pathway genes are differentially expressed in psoriatic plaques.
Their functional contribution to the pathophysiology of psoriasis needs
to be elaborated.Journal of Investigative Dermatology advance online
publication, 20 July 2006; doi:10.1038/sj.jid.5700488.
PMID: 16858420
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7474
-------------------------------------------------------------
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16858419&query_hl=2&itool=pubmed_docsum
Observations of Psoriasis in the Absence of Therapeutic Intervention
Identifies Two Unappreciated Morphologic Variants, Thin-Plaque and
Thick-Plaque Psoriasis, and their Associated Phenotypes.
* Christensen TE,
* Callis KP,
* Papenfuss J,
* Hoffman MS,
* Hansen CB,
* Wong B,
* Panko JM,
* Krueger GG.
1Department of Dermatology, University of Utah School of Medicine, Salt
Lake City, Utah, USA.
Psoriatic plaque thickness is a clinical measure of psoriasis severity.
We have observed that patients tend to revert to a baseline thickness
of psoriatic plaques when in an untreated state, and hypothesized that
other features of psoriasis could associate with this trait. Data
prospectively collected on 500 participants in the Utah Psoriasis
Initiative were used for the study. In response to a question assessing
plaque thickness when disease was at its worst, 144 (28.8%) reported
thick plaques, 123 (24.6%) reported thin plaques, and 233 (46.6%)
reported intermediate thickness. For patients with "worst-ever" disease
at enrollment (n=122), there was significant correlation of thickness
between assessment by the patient and the physician (r=0.448, P-value
0.01). Thick plaques associated with male gender, increased body mass
index, nail disease, psoriatic arthritis, larger plaques, more body
sites, and greater total body surface area affected. Thin plaques
associated with eczema, guttate psoriasis, and skin cancer. We suggest
that this is preliminary evidence that plaque thickness is an easily
measured trait that associates with other clinical features of
psoriasis, and that stratification on this phenotype may be useful in
further defining the genetic basis of this disease.Journal of
Investigative Dermatology advance online publication, 20 July 2006;
doi:10.1038/sj.jid.5700489.
PMID: 16858419
-----------------------------------------------------------------
IN my IP6 and psoriasis quest to understand the function of IP6 & P.
XOD is loaded with iron,
http://en.wikipedia.org/wiki/Xanthine_oxidase
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14738912&dopt=Abstract
Inhibition of xanthine oxidase by phytic acid and its antioxidative
action.
Muraoka S, Miura T.
Department of Biochemistry, Hokkaido College of Pharmacy,
Katsuraoka-cho 7-1, Otaru 047-0264, Japan.
We examined if phytic acid inhibits the enzymatic superoxide source
xanthine oxidase (XO). Half inhibition of XO by phytic acid (IC50) was
about 30 mM in the formation of uric acid from xanthine, but generation
of the superoxide was greatly affected by phytic acid; the IC50 was
about 6 mM, indicating that the superoxide generating domain of XO is
more sensitive to phytic acid. The XO activity in intestinal homogenate
was also inhibited by phytic acid. However, it was not observed with
intestinal homogenate that superoxide generation was more sensitive to
phytic acid compared with the formation of uric acid as observed with
XO from butter milk. XO-induced superoxide-dependent lipid peroxidation
was inhibited by phytic acid, but not by myo-inositol. Reduction of
ADP-Fe3+ caused by XO was inhibited by superoxide dismutase, but not
phytic acid. The results suggest that phytic acid interferes with the
formation of ADP-iron-oxygen complexes that initiate lipid
peroxidation. Both phytic acid and myo-inositol inhibited XO-induced
superoxide-dependent DNA damage. Mannitol inhibited the DNA strand
break. Myo-inositol may act as a hydroxyl radical scavenger. The
antioxidative action of phytic acid may be due to not only inhibiting
XO, but also preventing formation of ADP-iron-oxygen complexes.
PMID: 14738912
----------------------------
randall..
randall
Hi,
P news from around the world.
http://www.allheadlinenews.com/articles/7004304118
Pill Available To Fight Cancer, Sunburn
July 23, 2006 11:11 a.m. EST
Megan Shannon - All Headline News Staff Writer
(AHN) - An herbal pill will now available to help ease sunburn and help
the body fight against skin cancer.
Heliocare has been available in Europe for years but this summer is the
first time the pill will be available in major drug stores in the
United States.
The drug is made from extracts of a tropical fern and has been used for
skin conditions like psoriasis and eczema. Now it is being used to
treat sun damaged skin from the inside out.
Heliocare should be taken daily and it does not protect against sunburn
but rather helps when sunburn occurs. For this reason health experts
still recommend using sunscreen when being exposed to the sun.
Los Angeles dermatologist Dr. Jessica Wu said, "It gets into your blood
stream and works from the inside out, as opposed to sunscreen which
works from the outside in. So this pill mops up the damage that gets
past the sunscreen you might be wearing. It also repairs damage that is
done to you skin that leads to skin cancer."
Wu recommends that people take the pill every morning before they go
outside and an additional pill about a half an hour before being
exposed to the sun. She said the pills maximum benefits are realized
within two hours of taking the drug so an additional pill should be
taken every two hours.
This may pose a problem for those who cannot afford the going rate of
the drug--$60 for 60 pills.
---------------------------------------
http://www.heliocare.com/
&
http://groups.google.com/groups/search?q=Polypodium+leucotomos+psoriasis&qt_s=Search
Kalawalla goes by a bunch of names and is advertised in google as
organichope.com.
Strange how it protects against sun burn and the sun helps to rectify
psoriasis.
So, if your going to go out in the sun and your worried about skin
cancer,
for heaven's sake take the jungle fern pills along with you!
Less P and cancer protection both!
randall... what a deal.
randall
P news from around the world.
http://www.medicalnewstoday.com/medicalnews.php?newsid=47539&nfid=nl
Chronic Plaque Psoriasis Treatments Compared By Study
Oral psoralen -UV-A therapy was found to be more effective than
narrowband UV-B therapy in treating patients with chronic plaque
psoriasis, according to an article in the July issue of Archives of
Dermatology.
It is unclear whether narrowband UV-B (NB-UVB) therapy is as effective
as psoralen-UV-A (PUVA) therapy in treating psoriasis, according to
background information in the article. PUVA therapy includes the
combination of 8-methoxypsoralen medication (taken orally) and exposure
to UV-A (long-wave) radiation. NB-UVB involves exposure to UV-B
(short-wave) radiation and is thought to be safer than PUVA.
Sami S. Yones, M.Sc., and colleagues from King's College London
conducted a randomized, double-blind trial comparing the efficacy of
PUVA and NB-UVB therapies in treating chronic plaque psoriasis.
Ninety-three patients with moderate-to-severe cases of the disease were
recruited to participate in the study. Two hours before receiving UV
treatment, patients in the NB-UVB group took a placebo and those in the
PUVA group took 10-mg of 8-methoxypsoralen. Patients in both groups
attended sessions twice weekly until their skin cleared, up to a
maximum of 30 sessions. Patients whose skin cleared were followed up
until relapse or for 12 months.
In patients with skin types I through IV (skin more likely to burn),
PUVA was more effective than NB-UVB at clearing skin, with respective
84 percent vs. 65 percent clearance. Patients in the PUVA group also
achieved skin clearance in a significantly shorter number of
treatments, a median of 17 treatments, compared to 28.5 treatments in
the NB-UVB group. Nearly half of patients in the PUVA group experienced
erythema (redness of the skin) at some point during treatment, compared
to less than one-quarter in the NB-UVB group. Six months after skin
clearance was achieved, 68 percent of patients in the PUVA group were
still clear compared to 35 percent of patients in the NB-UVB group.
Overall, patients with skin types V and VI had a lower rate of
clearance than those with skin types I through IV (24 percent vs. 75
percent).
The authors write that despite the disadvantages of PUVA treatment
(i.e., may cause nausea, has the potential to cause skin cancer, cannot
be used during pregnancy), their results "suggest that PUVA compared
with NB-UVB tends to clear psoriasis more reliably, with fewer
treatments and for longer and should, therefore, still be used in
appropriate patients."
_____________________________________________
There is an abstract about menatetrenone (Vitamin K2) posted
in life extension today.
If your taking CoQ10 the vitamin K2 (k1, k3) is depleted by it. So
eating
plenty of green foods may restore the loss.
<http://www.thorne.com/altmedrev/.fulltext/8/3/303.pdf>
If you don't have a pdf reader. Try, (google:: lamson vitamin K)
http://www.herbalgram.org/herbclip/review.asp?i=43813
----------------------------------------------
P Abstracts today::
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16862176&query_hl=4&itool=pubmed_docsum
Novel roles of NM23 proteins in skin homeostasis, repair and disease.
* Braun S, Mauch C, Boukamp P, Werner S.
1Institute of Cell Biology, ETH Zurich, Honggerberg, Zurich,
Switzerland.
Keratinocyte growth factor (KGF) is an important regulator of epidermal
homeostasis and repair. Therefore, the identification of KGF target
genes in keratinocytes should contribute to our understanding of the
molecular mechanisms underlying these processes. In a search for
KGF-regulated genes, we identified the gene encoding the nucleoside
diphosphate kinase NM23-H1. Apart from a housekeeping function, NM23
proteins are involved in the regulation of many cellular processes as
well as in tumor metastasis, but their functions in epidermal
homeostasis and repair are largely unknown. Here, we show a high
expression of NM23-H1 and NM23-H2 in the KGF-responsive keratinocytes
of the hyperproliferative epidermis of mouse skin wounds and of
patients suffering from the skin disease psoriasis. To determine if
this overexpression is functionally important, we generated HaCaT
keratinocyte cell lines overexpressing NM23-H1 and/or -H2. Whereas the
enhanced levels of NM23 did not affect cell proliferation in
monoculture, NM23-H2 and double transfectants but not NM23-H1
transfectants formed a strongly hyperthickened epithelium in
three-dimensional organotypic cultures. The abnormal epithelial
morphology resulted from enhanced proliferation, reduced apoptosis and
alterations in the differentiation pattern. These findings suggest that
epidermal homeostasis depends on a tight regulation of the levels of
NM23 isoforms.Oncogene advance online publication, 24 July 2006;
doi:10.1038/sj.onc.1209822.
PMID: 16862176
This one is interesting.
Lets look at all the nm23's,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20nm23
This is good. Maybe or not, for us, (fits in well with my IP6 trial on
the face of it.)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16842238&query_hl=13&itool=pubmed_docsum
GTP in the mitochondrial matrix plays a crucial role in organellar iron
homeostasis.
* Gordon DM,
* Lyver ER,
* Lesuisse E,
* Dancis A,
* Pain D.
Mitochondria are the major site of cellular iron utilization for the
synthesis of essential co-factors such as iron-sulfur clusters and
heme. Here we provide evidence that GTP in the mitochondrial matrix is
involved in organellar iron homeostasis. A mutant of yeast
Saccharomyces cerevisiae lacking the mitochondrial GTP/GDP carrier
protein (Ggc1p) exhibits decreased levels of matrix GTP and increased
levels of matrix GDP (Vozza, A., Blanco, E., Palmieri, L., and
Palmieri, F. (2004) J. Biol. Chem. 279, 20850-20857). This mutant
(previously called yhm1) also manifests high cellular iron uptake and
tremendous iron accumulation within mitochondria (Lesuisse, E., Lyver,
E. R., Knight, S. A. B., and Dancis, A. (2004) Biochem. J. 378,
599-607). The reason for these two very different phenotypic defects of
the same yeast mutant so far remained elusive. We show that in vivo
targeting of a human nucleoside diphosphate kinase (Nm23-H4), which
converts ATP to GTP, to the matrix of ggc1 mutants restores normal iron
regulation. Thus, the role of Ggc1p in iron metabolism is mediated by
effects on GTP/GDP levels in the mitochondrial matrix.
PMID: 16842238
I'm not sure why i posted this next one.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15240699&dopt=Abstract
STAT1 regulates lipopolysaccharide- and TNF-alpha-dependent expression
of transporter associated with antigen processing 1 and low molecular
mass polypeptide 2 genes in macrophages by distinct mechanisms.
Marques L, Brucet M, Lloberas J, Celada A.
Macrophage Biology Group, Institute of Biomedical Research of
Barcelona, Barcelona Science Park, Universitat de Barcelona, Barcelona,
Spain.
Transporter associated with Ag processing 1 and low molecular mass
polypeptide 2 (LMP2) are essential for class I MHC function and share a
common bidirectional promoter. In murine bone marrow-derived
macrophages, LPS and TNF-alpha induced Tap1 and up-regulated Lmp2,
which is constitutively expressed at low levels. These two genes are
induced by LPS and TNF-alpha with distinct kinetics, at 6 and 12-24 h,
respectively. Using macrophages derived from the TNF-alpha receptors of
knockout mice, we found that induction by LPS is not due to the
autocrine production of TNF-alpha. In macrophages from STAT-1 knockout
mice, neither LPS nor TNF-alpha induced the expression of Tap1 or Lmp2.
The shared promoter contains several areas that can be controlled by
STAT-1, such as the proximal and distal IFN-gamma activation site (GAS)
boxes in the direction of the Tap1 gene. By making deletions of the
promoter, we determined that only the proximal GAS box is required for
LPS induction of Tap1 and Lmp2. In contrast, TNF-alpha induction of
these two genes is dependent on the IFN regulatory factor-1 and
NF-kappaB boxes, and not on the GAS box. Our experiments using gel
shift analysis and Abs indicated that STAT1 binds to the GAS box in
nuclear extracts from LPS-treated macrophages. The nuclear extracts
obtained from macrophages treated with TNF-alpha bound to the IFN
regulatory factor-1 and NF-kappaB boxes. These results show that LPS
and TNF-alpha regulate the induction of Tap1 and Lmp2 through STAT1,
but use distinct areas of the promoter.
PMID: 15240699
Oh, LPS, TNF and STats with IfN is back on my radar.
What's the gut connection with P? I don't know. Let's find one.
WE do have the litaf gene,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=9516
http://www.ibdjournal.com/pt/re/ibd/abstract.00054725-200607000-00007.htm;jsessionid=GGvbXcbvTMndMgYBzHxnKLG12xFQG2XcKXkZ4XwmsJg3G71wVqkP!1941873617!-949856145!8091!-1
A New Transcription Factor that Regulates TNF-[alpha] Gene Expression,
LITAF, Is Increased in Intestinal Tissues from Patients with CD and UC.
Original Articles
Inflammatory Bowel Diseases. 12(7):581-587, July 2006.
Stucchi, Arthur PhD *; Reed, Karen PhD *; O'Brien, Michael MD, MPH +;
Cerda, Sandra MD +; Andrews, Charles MD +; Gower, Adam MS *; Bushell,
Kristen BS ++; Amar, Salomon DDS, PhD [S]; Leeman, Susan PhD ++;
Becker, James MD *
Abstract:
Background: The proinflammatory cytokine tumor necrosis factor-[alpha]
(TNF-[alpha]) plays a key role in the pathogenesis of Crohn's disease
(CD) and ulcerative colitis (UC). Recently, a new transcription factor
termed LITAF (lipopolysaccharide-induced TNF-[alpha] factor) was shown
to mediate TNF-[alpha] expression in human macrophages by direct
binding to specific sequences in the promoter region of the TNF-[alpha]
gene.
Methods: In this report, we identified LITAF in resected ileal and
colonic tissues from patients with CD and UC by immunohistochemistry,
real-time polymerase chain reaction, and Western blot analysis. LITAF
expression in inflamed and noninflamed areas of the tissues was
compared.
Results: This is the first demonstration of LITAF, a newly discovered
transcription factor that regulates TNF-[alpha] gene transcription in
ileal and colonic tissues from patients with either CD or UC. LITAF
immunostaining was localized to lamina propria macrophages and was
markedly increased relative to tissues from controls without
inflammatory bowel disease. In patients with CD, a 5-fold increase in
LITAF mRNA was measurable in noninflamed colonic tissues compared with
controls without inflammatory bowel disease. LITAF mRNA in tissues from
inflamed areas of the colon was increased by an additional 60% compared
with noninflamed tissues. In patients with UC, LITAF mRNA levels in
colonic tissues resected from noninflamed areas were elevated 15-fold
above nondisease controls, but they were not different in tissues
resected from inflamed areas. Western blot analysis showed that in
patients with CD, there was a marked increase in LITAF protein in
inflamed areas compared with noninflamed areas. LITAF protein levels
were not different between noninflamed and inflamed tissues obtained
from patients with UC. TNF-[alpha] mRNA and protein levels paralleled
LITAF. Similarly, in inflamed ileal tissues from patients with CD,
LITAF is also localized to lamina propria macrophages. LITAF mRNA and
LITAF protein were significantly increased in inflamed ileal tissues
compared with noninflamed areas.
Conclusions: LITAF is readily detectable in ileal and colonic tissues
from patients with either CD or UC, is significantly elevated above
controls, and is localized to macrophages, a major source of
TNF-[alpha]. These data provide strong evidence of a role for LITAF in
the pathophysiological regulation of the TNF-[alpha] gene and
underscore the potential value of anti-LITAF strategies in the clinical
management of these diseases.
---------------------------------------------------------------
And we know most severe psoriatics have alcohol problems that will
increase TNF levels.
http://www.comparative-hepatology.com/content/figures/1476-5926-2-S1-S31-1.jpg
from
http://www.comparative-hepatology.com/content/3/S1/S31
Lipopolysaccharide-mediated signal transduction: Stabilization of
TNF-alpha mRNA contributes to increased lipopolysaccharide-stimulated
TNF-alpha production by Kupffer cells after chronic ethanol feeding
Alcoholic liver disease (ALD) develops in approximately 20% of all
alcoholics with a higher prevalence in females [1]. The development of
fibrosis and cirrhosis is a complex process involving both parenchymal
and non-parenchymal cells resident in the liver, as well as the
recruitment of additional cell types to the liver in response to damage
and inflammation [2]. Kupffer cells, the resident macrophages in the
liver, are critical to the onset of ethanol-induced liver injury.
Ablation of Kupffer cells prevents the development of fatty liver and
inflammation, early events in the progression of ethanol-induced liver
damage, in rats chronically exposed to ethanol via intragastric feeding
[3]. Endotoxin (or lipopolysaccharide (LPS)), a component of the cell
wall of gram-negative bacteria, is an important activator of Kupffer
cells, stimulating the production of inflammatory and fibrogenic
cytokines, as well as reactive oxygen species. LPS concentration is
increased in the blood of alcoholics [4,5] and rats exposed to ethanol
via intra-gastric infusion [6], probably due to impaired barrier
function of the intestinal mucosa [7]). In a series of elegant
experiments using transgenic animals from the laboratory of Ron
Thurman, a working model for the development of alcoholic liver disease
has been developed. This model proposes that increased exposure of
Kupffer cells to LPS during chronic ethanol consumption results in
increased production of inflammatory mediators, in particular TNF-alpha
and reactive oxygen species, leading to the progression of fatty liver,
inflammation and fibrosis, characteristic of ALD [7]. In addition to
this increased exposure of Kupffer cells to LPS in response to ethanol,
we and others have shown that chronic ethanol also sensitizes Kupffer
cell responses to LPS [8,9]. We hypothesize that increased sensitivity
to LPS stimulation after chronic ethanol exposure likely contributes to
the progression of liver injury.
Role of TNF-alpha in the progression of alcoholic liver disease
TNF-alpha is thought to play a particularly critical role in the
pathogenesis of ALD. TNF-alpha is one of the principal mediators of the
inflammatory response in mammals, transducing differential signals that
regulate cellular activation and proliferation, cytotoxicity and
apoptosis [10,11] In addition to its role in acute septic shock,
TNF-alpha has been implicated in the pathogenesis of a wide variety of
inflammatory diseases [11,12,14] as well as in the progression of
alcoholic liver disease [7,15] The role of TNF-alpha in the development
of ethanol-induced liver injury has been well characterized in animal
models [7,15]
Production of TNF-alpha is one of the earliest responses of the liver
to injury [15]. Circulating TNF-alpha is increased in the blood of
alcoholics and in animals chronically exposed to ethanol [16,17].
Antibiotic treatment decreases TNF-alpha expression and ethanol-induced
liver injury in rats exposed to ethanol via intra-gastric infusion [7],
suggesting that increased TNF-alpha after ethanol exposure is due, at
least in part, to increased exposure to LPS. In addition to increasing
LPS exposure, chronic ethanol also increases sensitivity to LPS. For
example, long-term ethanol consumption increases the susceptibility of
rats to endotoxin-induced liver injury [8,18]. Moreover, we have shown
that LPS-stimulated TNF-alpha secretion is increased in Kupffer cells
isolated from rats fed ethanol in their diet for 4 weeks compared to
pair-fed controls [9,19,20].
Regulation of LPS-stimulated TNF-alpha production
Production of inflammatory cytokines is a highly regulated process;
regulation has been reported at the level of transcription, translation
and secretion [21,22]. Transcriptional activation of TNF-alpha by LPS
requires the activation of a distinct set of transcription factors
binding to at least two regions of the TNF-alpha promoter which include
NF kappa B, Egr-1 and AP-1 binding sites [23] (Figure 1) [24]. While
the exact array of transcription factors interacting with the TNF-alpha
promoter is to some extent cell and species specific [25], recruitment
of NF kappa B and early growth response 1 protein (Egr-1), as well as
increased c-jun binding to a CRE/AP-1 site, appear to be required for
full activation of TNF-alpha expression in most types of macrophages
[23,24]. Activation of each of these nuclear transcription factors is
mediated by specific LPS-mediated signaling cascades (Figure 1). LPS
binds to a cell surface receptor, CD14, which, via interactions with
the toll-like receptor 4 (TLR4) [26], stimulates a complex array of
signal transduction cascades [27,28] Stimulation of macrophages with
LPS activates tyrosine kinases, protein kinase C, nuclear factor kappa
B (NF kappa B), as well as members of the mitogen activated protein
kinase family, including ERK1/2 (extracellular receptor activated
kinases 1/2), p38 and c-jun N-terminal kinase (JNK) [27].
Ethanol disrupts a number of hormone and neurotransmitter dependent
signaling pathways [29], including many of the same signaling pathways
activated by LPS in macrophages. In a series of recent experiments, we
have found that chronic ethanol feeding disrupts specific
LPS-stimulated signal transduction pathways which regulate both
TNF-alpha transcription and mRNA stability in Kupffer cells [19,20,30].
Chronic ethanol had complex effects on the regulation of LPS-stimulated
TNF-alpha mRNA transcription; the transcriptional activity of NF kappa
B was dramatically decreased, but this was compensated for by increased
Egr-1 activity [19,30]. Despite these complex changes, chronic ethanol
exposure had no net effect on the rate of TNF-alpha transcription [20].
Therefore, we hypothesized that increased LPS-stimulated TNF-alpha mRNA
accumulation in Kupffer cells isolated from rats chronically exposed to
ethanol might be due to a stabilization of TNF-alpha mRNA.
<sniP>
More to consider,
http://dir.niehs.nih.gov/dirln/dirpha/projects.htm
Plus more,
http://inet.uni2.dk/~iirrh/IIR/08vasc/sepCK.htm
[...]
endotoxin (LPS), triggers production of proinflammatory cytokines (TNF,
IL-1) and monocyte adherence to endothelial cells. TNF and IL-1 also
activates neutrophils and endothelial cells for increased adherence.
All activated cells release secondary inflammatory mediators, including
cytokines. Activation of platelets and increased production of
procoagulants by endothelial cells may trigger microthrombosis. In some
cases, disseminated intravascular coagulation (DIC) may occur with
life-threatening tissue ischemia.
Vessel dilation caused by free radicals, histamine, prostaglandins,
prostacyclin, and the kinin and tachykinin family of molecules,
combined with the effects of cytokines on the endothelial cells,
contribute to increased vascular permeability for fluids and
low-molecular weight substances, causing oedema. If the process is
wide-spread, a capillary leak syndrome may result. In some cases,
erythrocytes may leak out and cause bleeding.
You don't have to be french to get it,
http://anne.decoster.free.fr/immuno/dico/41lps.htm
----------------------------------------------------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=47508&nfid=nl
Patients with Crohn's disease of the colon have one copy less than
healthy persons of the beta-defensin 2 gene, a gene coding for an
important defense molecule of the body. An international research team
comprising scientists of the Robert Bosch Hospital in Stuttgart and the
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
in Heidelberg have discovered a possible cause of the chronic
inflammations.
Crohn's disease (CD) is a chronic inflammatory disease of the
intestinal tract affecting most commonly the lower part of the small
bowel, called the ileum, and the colon. The cause of the disease is
unknown; genetic and environmental factors have been suggested to play
a role.
Defensins are part of the arsenal of defense weapons used by the human
immune system. The peptides consist of only about 30 protein building
blocks and act like our body's own antibiotics that protect the mucous
membranes from bacterial invasion. Patients with Crohn's disease of the
colon (colonic CD) have a lower level of beta-defensins in the mucous
membranes. In a collaborative research project headed by Dr. Klaus
Fellermann and Professor Eduard F. Stange, Robert Bosch Hospital,
Stuttgart, researchers from the German Cancer Research Center and the
Universities of Vienna and Davis, California, have now discovered that
the number of defensin gene copies has a crucial influence on the
development of the disease.
Defensin genes are arranged in nests, called clusters, on chromosome 8.
The number of clusters varies considerably across the population; this
is technically called a polymorphism. The research team has now shown
that patients with colonic CD have on average only three copies of the
gene encoding beta-defensin 2, whereas healthy control persons as well
as patients with small bowel CD or ulcerative colitis, another
inflammatory bowel disease, have an average of four copies of this gene
per cell. The researchers showed that a lower number of gene copies is
indeed associated with reduced production of the endogenous antibiotic,
which explains the known low defensin level. They presume that this
causes the defense of the intestinal mucous membrane to become porous
so that bacteria can attach to and invade the mucous membrane, which
leads to the typical inflammatory hot spots of Crohn's disease.
The disease, which is named after American physician Dr. Burrill
Bernhard Crohn, is characterized by recurring episodes of active
disease. It affects approximately 150,000 people in Germany; five new
cases per 100,000 inhabitants are diagnosed each year. There has been a
substantial rise in incidence rates in recent years. Patients suffering
from Crohn's disease also have an elevated risk of developing bowel
cancer.
About the DEUTSCHES KREBSFORSCHUNGSZENTRUM
The Deutsches Krebsforschungszentrum (DKFZ) Heidelberg was founded as a
non-profit organization and supraregional research center by the Land
(state) Baden-Wuerttemberg in 1964. It was constituted as a foundation
of public law. Since 1975, it has been a Großforschungseinrichtung
(National Research Center). It is mainly funded by the
Bundesforschungsministerium (Federal Ministry for Research and
Technology) (90 %) and by the Ministerium fuer Forschung und
Wissenschaft (Ministry for Research and Sciences) of the Land
Baden-Wuerttemberg (10 %). Additional funding is obtained by other
public and private sources e.g. the Deutsche Forschungsgemeinschaft
(German Science Association), special projects of the European Union
(EU), of Federal and State ministries as well as cooperations with the
industry and also private donations to the foundation. In accordance
with its Statutes and Articles, it is the task of the Center to engage
in cancer research. "Cancer research", a term which every discipline
defines quite differently. In a center with a multi-disciplinary
structure, the discussion about the research program is a continuous
balancing process.
DEUTSCHES KREBSFORSCHUNGSZENTRUM
Im Neuenheimer Feld 280
69120 Heidelberg
---------------------------------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=47543&nfid=nl
First-ever Criteria For Distinguishing Sun Damage From Early Melanoma,
Providing Guidelines To Lessen Removal Of Healthy Tissue
A Mayo Clinic physician and colleagues have defined the normal number
of melanocytes that are present in Caucasians' sun-exposed skin. Until
now, there has not been a criterion to distinguish sun damage from
early (in situ) melanoma. Results of the study, which shed light on
this undefined area in skin cancer, are available in the July issue of
Archives of Dermatology.
"There are many uncertainties in medicine. In many instances these
uncertainties lead to overly aggressive treatments," says Ali Hendi,
M.D., Mayo Clinic dermatologic surgeon and lead investigator of the
study. "We didn't have an accurate way to distinguish cancer from
over-exposed but normal skin, and this study was designed to find the
missing link."
There are two basic types of skin cancer, non-melanoma, which includes
basal cell and squamous cell cancers, and melanoma. Melanoma is the
deadliest, reports the American Cancer Society, accounting for only 4
percent of diagnosed skin cancers, but nearly all of the deaths. It
originates in melanocytes, the cells that produce melanin, which colors
skin, hair and eyes.
Dr. Hendi's team thought that pathologists and Mohs surgeons may err on
the side of over-diagnosing melanoma in sun-damaged skin, leading to
additional and unnecessary surgery, complications or deformity. Mohs
surgery, named for Frederic E. Mohs, M.D., who developed the technique,
allows incremental removal of skin cancers, reducing removal of tissue
to just the diseased areas. Mohs surgeons remove a thin section of the
tumor, review its pathology under a high-powered microscope and are
able to stop tissue removal as soon as the edge of the diseased tissue
is reached. Because of this assumption of overly cautious surgery, the
researchers decided to develop criteria by which cell changes that can
indicate noncancerous sun damage can be distinguished from those which
indicate melanoma.
In the study, disease-free tissues samples were obtained from 132
randomly selected Caucasian patients undergoing Mohs surgery for
non-melanoma skin cancers of the face and neck. The samples were cut
from the edges of the excised area, and consisted of normal,
noncancerous skin. They found that in normal sun-exposed skin, the
number of melanocytes in a 0.5 millimeter (mm) diameter was 15.6 (as
opposed to undamaged skin that might have five to seven). Adjacent
melanocytes, another indicator used by pathologists to diagnose early
melanoma, were present in varying degrees in all but 11 percent of the
samples. Finally, melanocytes were found to descend along the hair
follicles, a finding previously attributed only to melanoma in
sun-damaged skin. The researchers say these findings are significant
because many surgeons remove tissue until they reach undamaged cells
with "normal" melanocyte distribution.
Dr. Hendi predicts the study's findings will be valuable to doctors who
diagnose and treat melanoma. "To be able to look in the microscope and
have a measurement by which to determine successful removal of melanoma
in situ is something we've hoped for quite a while," he says. "In many
cases, surgeons can stop removing tissue much sooner, which will result
in less trauma to the skin." Dr. Hendi's team recommends doctors use
the study's findings as their new baseline for melanoma diagnosis and
tissue removal.
###
Dr. Hendi collaborated with David Brodland, M.D., and John Zitelli,
M.D., both from the University of Pittsburgh Medical Center. This study
was funded in part by the Skin Cancer Foundation Frederic E. Mohs
Memorial Award.
More information on melanoma treatment at Mayo Clinic is available at
http://www.mayoclinic.org/melanoma, and information on current melanoma
research programs is online at
http://mayoresearch.mayo.edu/mayo/research/melanoma.
Mayo Clinic is now using Pathfire's Digital Media Gateway (DMG) for
distribution of video news releases, to streamline our services and
provide station staff with content that is easily accessible when they
need it. On the left side of the DMG main page, click on the VNF Master
Locator and search for MayoClinic0055, or look for the resources in the
Video News Provider B section. If you have questions or problems in
locating the story, contact Pathfire Customer Support at
sup...@pathfire.com. If you do not have access to Pathfire's DMG, and
would like access to Mayo Clinic's video resources by satellite or
other means, please e-mail: sultz...@mayo.edu.
-------------------------------------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=47830&nfid=nl
Acquired susceptibility is an important, but until now often ignored,
potential cause of disease. In a commentary article published today in
the open access journal Environmental Health, professors Paolo Vineis
and David Kriebel emphasize that the interaction between environments
and genes is a fundamental characteristic of the causal processes
leading to disease. But they find that recent research on
gene-environment interactions has failed to include acquired
susceptibility to disease as part of the causal perspective. For
example, susceptibility to cancer may be acquired in the womb or in
early life and could be mistaken for genetic predisposition. The
effects of preventable environmental factors may then be wrongly
attributed to inherited traits. This concept has fundamental
implications for the interpretation of research in epidemiology and
deserves attention from the scientific community.
###
Article:
Notes on causality and susceptibility to disease
Paolo Vineis and David Kriebel
Environmental Health: A Global Access Science Source 2006, (in press)
Journal website: http://www.ehjournal.net/
Contact: Juliette Savin
BioMed Central/
---------------------------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=47587&nfid=nl
What You Eat May Fuel Cancer: Medical Experts Advise A Diet Rich In
Omega-3s And Phytonutrients To Help Fight The Disease
If you want to reduce your risk for getting cancer, heart disease,
diabetes and a host of other diseases, the message is clear - eat a
nutrient-rich, low-fat, high fiber diet, with plenty of fruit and
vegetables. So why is this wisdom forgotten when a person is diagnosed
with cancer, and the standard advice becomes: "Eat whatever you want,
whatever you can tolerate," even when this may include a diet high in
fat and refined sugars.
According to two of the country's leading authorities on cancer and
nutrition, David Katz, MD and Keith Block, MD, the typical American
high-fat, empty calorie diet can set the stage for an inflammatory
response that actually fuels a cancer patient's disease, undermines
treatment, and promotes malnutrition.
"Cancer generates the production of low-grade inflammatory molecules
that breakdown lean muscle, and can disrupt immune functioning. The
heavy consumption of fats, refined flours and sugars found in the
traditional American diet can increase this inflammation, contributing
to a lack of appetite, more debilitating weight loss, and actually
promote the very disease the patient is trying to fight," explains
Keith I. Block, MD, Medical/Scientific Director of the Block Center for
Integrative Cancer Treatment in Evanston, Illinois.
In fact, in many cases it's not cancer that kills patients. According
to The National Cancer Institute, some 20% to 40% of cancer patients
die from complications of malnutrition, and 80% of patients will
develop some form of clinical malnutrition. And even relatively small
degrees of under-nutrition can seriously undermine a cancer patient's
health and are associated with a marked increased risk of hospital
admissions and death.
"Cancer may kill, in part, by causing starvation and conventional
therapies may actually exacerbate this aspect of the disease," says
ABC News medical contributor and nationally renowned authority on
nutrition, David Katz, MD. "While these treatments can effectively
attack the cancer, they may kill the patient in the process of doing
so." Katz, an Associate Professor of Public Health and director of
the Yale prevention Research Centers adds: "There is thus a need to
combine effective assaults on cancer, with effective nurturing, and
nourishing, of the body. Optimizing nutrition during and following
cancer therapy is unquestionably a vital element in overcoming the
disease, and reclaiming good health."
So what kind of a diet can fight malnutrition and help a cancer patient
combat their disease Drs. Block and Katz offer the following
suggestions:
Include cancer and inflammation-fighting phytonutrients, found in
abundance in many fruits and vegetables - berries, grapes, cherries,
brussel sprouts, broccoli, collards, kale, carrots, spinach, garlic and
onions.
Eat or supplement with Omega-3 fatty acids, found in cold water fish
such as salmon, trout and tuna.
Choose complex carbohydrates, such as brown rice, barley, quinoa, and
other whole grains.
Eat healthy sources of proteins such as fish legumes, soy, and whey
protein, and use "healthy" oils such as flaxseed, canola, walnut,
and pumpkin seed.
Choose energy dense/nutrient dense foods such as avocado; nut butters;
and soy.
Avoid "bad" dietary fats such as saturated fats found in milk,
cheese, butter, red meat, pork, coconut, and poultry.
Eliminate unnatural fats, called trans fat, found abundantly in
margarine, hydrogenated oils, as well as many baked goods and
convenience foods.
Reduce or eliminate simple carbohydrates such as sugar, honey, high
fructose corn syrup, concentrated sweeteners, sugary beverages,
cookies, cakes, pastries, white bread, crackers and white-flour baked
goods. These are high-glycemic foods that cause a sudden rise in blood
sugar and ultimately increase inflammation.
The Block Center for Integrative Cancer Care and Optimal Health,
located in Evanston, Illinois, was founded in 1980 by Penny and Keith
Block, M.D. with a focus on treating the patient as a whole person, not
simply treating the diagnosis. The Center's research-based treatment
integrates an innovative approach to the best of conventional medicine
with scientifically sound complementary therapies -- therapeutic
nutrition, botanical and phytonutrient supplementation, prescriptive
exercise, and systematic mind-body strategies, to enhance the recovery
process. Block has pioneered this "middle ground" approach to cancer
care and optimal health - designing a total treatment plan that is
tailored to the precise needs of each patient, using a unique set of
clinical and laboratory assessments. The Block Center is breaking new
ground with the creation and development of Cancer Rehab as an
innovative treatment modality, and is currently the only private North
American medical center using chronomodulated chemotherapy. Dr .Block
is a member of the National Cancer Institute's PDQ Cancer Complementary
and Alternative Medicine (CAM) Editorial Board in Washington, D.C., and
Director of Integrative Medical Education at the College of Medicine at
the University of Illinois, Chicago. The Block Center is a full
treatment clinic, has served as a CCOP site through the National Cancer
Institute, and is currently engaged in clinical cancer research with
the University of Illinois and other university facilities in the
United States and Israel (http://www.blockmd.com).
David L. Katz, MD, is a nationally renowned authority on nutrition,
weight control, and the prevention of chronic disease. His ninth and
most recent book, The Flavor Point Diet (Rodale: January, 2006)
introduces a groundbreaking strategy for weight control based on the
thoughtful distribution of flavors. He is an Associate Professor of
Public Health and directs the Yale Prevention Research Center. He is
Medical Contributor for ABC News, with weekly appearances on Good
Morning America, and occasional appearances on 20/20, World News
Tonight, and other programming. In 2005, Dr. Katz became a syndicated
health/nutrition columnist for The New York Times.
-------------------------------------------------------------------------------
randall...
randall
P news from around the world.
http://releases.usnewswire.com/GetRelease.asp?id=69870
Psoriasis Group Asks Farrar, Straus and Giroux to Make Corrections to
Future Editions of Rich Cohen's Memoir 'Sweet and Low'
7/27/2006 7:30:00 AM
To: National Desk, Health and Arts Reporters
Contact: Michael Paranzino of Psoriasis Cure Now, 202-253-4863 or
mic...@psorcurenow.org; Web: http://www.psorcurenow.org
KENSINGTON, Md., July 27 /U.S. Newswire/ -- "Psoriasis Cure Now," a
nonprofit patient advocacy group, has asked Farrar, Straus and Giroux,
publisher of Rich Cohen's family memoir "Sweet and Low," to correct
inaccuracies in its depiction of psoriasis in future editions of the
book. The memoir tells the story of how Cohen's grandfather amassed a
fortune in Brooklyn by inventing the popular sugar substitute, and how
Cohen's immediate family was ultimately disinherited, costing them tens
of millions of dollars. One of Cohen's aunts is portrayed as a
malevolent force in the book, and the errors arise in depictions of her
psoriasis and psoriatic arthritis, diseases that the book trivializes
and portrays incompletely.
"Rich Cohen was aiming for his aunt, but he hit millions of Americans
with psoriasis and psoriatic arthritis instead," said Michael
Paranzino, president of Psoriasis Cure Now. "The book's attempt to
minimize the seriousness of these diseases does a disservice to
psoriasis patients and weakens an otherwise engaging and entertaining
read. We hope the mistakes are corrected for the paperback edition."
The book, despite its footnotes and air of authority, does not portray
psoriasis accurately. Most egregiously, the book states: "even in the
worst cases, the disease (psoriasis) is simply not disabling. It is
suffered instead as a chronic annoyance..." Later in the same paragraph
Cohen cites the book Essential Pathology, but does not include this
pivotal sentence from Essential Pathology that flatly contradicts
Cohen: "The severity of the disorder varies from annoying, scaly
lesions over the elbows to a serious, debilitating disorder involving
most of the skin and often associated with arthritis." Psoriasis most
certainly can be disabling.
The book also cites a junior high textbook suggesting that psoriasis is
an outward expression of subconscious problems, but Cohen ignores the
well-known genetic links and immune system underpinnings of psoriasis
that even a few minutes of research would have turned up. A full
examination of the book's flawed depiction of psoriasis is available on
the Psoriasis Cure Now website at
http://www.psorcurenow.org/sweetandlow.php , and the book will be
discussed in the next Psoriasis Cure Now Podcast to be released August
8.
"Sweet and Low is a fun book that also aims to educate, with lengthy
examinations of history, science and culture," Paranzino added. "This
makes the false depiction of psoriasis even more troublesome, as
readers will assume that a footnoted book such as this gets it right.
The 'heartbreak of disinheritance' is no excuse for shoddy research.
Psoriasis is a serious and often debilitating disease, one that can run
in families. For the author's sake, we hope he did not inherit any
psoriasis susceptibility genes from the very relatives who disinherited
him from their fortune."
Psoriasis is an incurable, non-contagious disease of the immune system
that can first strike at any age, causing painful skin lesions, and
often, arthritic symptoms. A 1999 study found that psoriasis causes
reductions in physical and mental functioning comparable to that seen
in diabetes, heart disease, hypertension, depression and other
diseases. As many as 7.5 million Americans have psoriasis.
---------------------------------------------------------------------------------------
What was it that Ross Perot said about the crazy aunt in the basement?
lol
randall... everyone has one? 2% have P and some may be severe?
randall
P News from around the world.
What skin condition is worse then psoriasis and afflicts 12,000 in the
US?
Doesn't seem to be any question about it being a genetic disorder.
http://www.nctimes.com/articles/2006/07/30/lifeandtimes/72806131757.txt
[...]
The rare, incurable genetic skin disorder known as EB affects 12,000
people in the United States and causes severe blistering inside and
outside the body, making the epidermis fragile enough to fall off with
a simple rub. The disease is not specific to race and afflicts both
boys and girls.
Each year in junior high, Cristina gave a presentation on EB for her
classmates, something she said alienated many of them.
"A lot of people just chose to ignore me," said Cristina, while
watching television in the apartment that she shares with her mother in
the southwest San Marcos community of San Elijo Hills. "Instead of
staring, they would just act like I wasn't there."
Weighing less than 70 pounds, with her pale complexion, the red and
purple sores, and seated in a wheelchair, it was difficult to fit in,
she said.
As well, the lack of nutrients in Cristina's body kept her from going
through puberty -- her body remains that of a young girl.
Those afflicted with recessive dystrophic EB, such as Cristina, have a
difficult time absorbing nutrients and gaining weight. The nutrients
that her body does absorb are used to heal the wounds.
Cristina said people thought her high-pitched, soft voice was that of a
child -- no one knew it was the result of severely scarred vocal
chords.
As she has aged, Cristina said many of her physical disabilities have
gone beyond being a frustration.
They are unbearable.
At restaurants, waiters automatically give her a child's menu. At the
mall, she goes straight to a young girl's apparel store, Limited Too.
When telemarketers call, they refuse to believe she is a 23-year-old
adult able to make her own decisions about their products.
And her deformities have made it all but impossible to make friends and
build a social life.
Over the years, her hands have taken the shape of a fist -- her fingers
fused together from years of tissue scarring. Only two protruding
thumbs remain.
At 16, she had all but three of her teeth pulled to keep them from
decaying because of the lack of nutrition.
These days, her smiles are limited.
"It's hard to talk to people," said the soft-spoken Cristina. "So I
just don't try to most of the time."
Instead, she has focused on the bigger picture: teaching people about
her disease to rid them of ignorance.
This is her life's mission.
"I'm just thankful I am still alive, I don't want to waste any moment,"
said Cristina. "Mentally, I've learned to just deal with it. I don't
want anyone to feel sorry for me, I just want them to know about EB."
Cristina's crusade
<sniP>
------------------------------------------------------------------------------------------
OK. This EB sounds really bad.
Is there anything Cristina can eat that would help?
http://www.hsrmagazine.com/articles/681feat1.html
Posted on: 07/27/2006
Basic Instinct: Immunity
Protecting the body from harm is a natural instinct requiring natural
solutions
by Steve Myers
"Self-preservation is the first law of nature." ~ British poet
Samuel Butler Protecting the human body is an around the clock task.
There are certain times and seasons of greater malcontent, but health
and self-preservation are tested every second of every day of every
month. Keeping the immune system in tip-top shape is no easy chore,
given the complexities of the involuntary immune response; but, in
addition to healthy diet changes, dietary supplements can help address
general immune health, as well as target specific aspects of illness
prevention and severity.
Learning about something as complex as the immune system can be
daunting, but as with most high level education, repetition rules.
Staying up-to-date on the mechanisms of the immune system and its many
active parts is the best way for a retailer to both understand the
actions of various supplements and, in turn, educate customers while
making suggestions on possible natural remedies.
The basic outside threats to human health are either viruses or
bacteria. These are called antigens. Other usually innocuous substances
can trigger an autoimmune response, such as in the case of allergies.
The first line of defense against such antigens, whether pathogenic
(harmful) or not, is the innate immune response, which is normally a
birthright. At this level, the immune system uses various tools located
or delivered to sites or membranes that interface with the outside
world. The skin has a blood supply rich in immune cells and can secrete
antimicrobial substances; membranes lining the eyes, nose, mouth,
throat and other body openings contain immune cells and enzymes that
help prevent antigens from reaching the inner body; mucus traps
antigens, which are then carried by rhythmic cilia up the throat for
expulsion; the eyes secrete tear drops, which contain the enzyme
lysozyme to break down harmful bacteria; saliva in the throat is also
laden with antibacterial substances; and stomach acid often halts
antigens before they can be absorbed.
However, these innate protections are not impenetrable, and the immune
system has developed tools to confront antigens that make it deeper
into the body. Chief among these weapons are numerous different white
blood cells, each with its own special power and assignment. It is
important to have a decent understanding of these immune cells, as most
research on supplements focuses on levels and activities of these
cells.
White blood cells, also called leukocytes, are created in bone marrow
from stem cells. Forming the frontline are monocytes, which move from
blood to tissue and become macrophages, huge cells that seek and
destroy pathogens. Langerhans cells in skin are an example of a
monocyte.
The granulocyte group includes basophils and eisonophils, which handle
parasites in the lungs and skin, and produce histamine, which
stimulates inflammation. Also included are neutrophils, the most
abundant white blood cell in the body and adept hunters and slayers of
pathogens.
Perhaps the most known immune cells to followers of health research are
lymphocytes, including T cells and B cells. T cells go from the marrow
to the thymus, while B cells head to the blood. These cells are a
formidable team. Each B cell identifies a specific virus or bacteria
then releases swarms of antibodies for that specific threat. However, B
cells cannot penetrate antigens; they only bind to them. T cells find
cells infected with identified antigens and destroy the antigens with
direct brute force. Certain T cells, including helper T cells, assist B
cells by producing cytokines, including interferon, that activate
antibody production. Interferon, which is also produced by macrophages,
interferes with viruses, curbing virus replication.
Another key immune cell is the Natural Killer (NK) cell, which not only
hunts cancer and tumor cells for the innate immune response, but also
releases cytokines and other chemicals to trigger the antigen immune
response.
Dietary supplement ingredients, including vitamins, minerals,
antioxidants, herbs and specialty substances, address the production
and activity of these various immune cells, and have been shown to
benefit certain areas of immune function, including specific maladies.
As a healthy immune system starts with a proper diet, basic nutritional
components are key to self-preservation. Cornell University researchers
reported nutritional deficiencies may weaken immune response,
especially in younger years but possibly over an entire lifetime.1 They
particularly noted the importance of vitamins, minerals, antioxidants
and probiotics.
Deficiency of B vitamins, specifically B6, has been associated with
decreased production of various lymphocytes and interleukin-2 (IL-2), a
protein cytokine that promotes the proliferation of CD4 T cells.2 In
fact, Oregon State University researchers found improved B6 status in
women correlated to increased lymphocyte proliferation.3 Similarly,
inositol hexaphosphate (IP6), considered a B vitamin, impacts secretion
of IL-8, a chemokine that affects neutrophil activity.4 IP6 also
promotes inflammatory response in macrophages, where IL-8 is produced,5
a mechanism that has shown promising anti-tumor effects.6
Equally important to immune cells is vitamin C, which is indicated in
production of both interferon and antibodies. It also protects
neutrophils from oxidation.7 Part of vitamin C's protective benefit
is due to its antioxidant action. Oxidative stress increases the
antioxidant requirements of the white blood cell macrophages and
lymphocytes.8 Vitamin C supplementation increases antioxidant
glutathione concentration in lymphocytes,9 and normalizes monocyte
adhesion to endothelial cells.10 Long used against the elusive common
cold, vitamin C has shown mixed results in cold prevention, according
to a major review.11 However, a 2002 study involving 180 British
subjects found vitamin C supplementation (as Ester- C®, from Zila
Nutraceuticals) could prevent the common cold, as well as limit severe
symptoms and shorten the duration.12
Fellow antioxidant vitamin E is thought to protect the thymus and
various immune cells from oxidative stress. In fact, research shows
vitamin E plays an important role in the differentiation of immature T
cells in the thymus, inducing higher differentiation that results in
improved cellular immunity.13 And high-dose (1,500 mg/d)
supplementation was shown to increase macrophage and lymphocyte
chemotaxis, superoxide (SO) anion production and lympho-proliferative
capacity.14 However, even low-dose vitamin E supplementation (200 IU/d)
has shown the ability to protect the elderly from upper respiratory
tract infections and reduced the rate of multiple infections.15
Researchers from Creighton University Medical Center in Omaha, Neb.,
concluded vitamin E, along with vitamin A, exhibited an overall
protective effect on acute toxicity and oxidative stress associated
with thymus health.16
On its own, vitamin A contributes to production of T helper cells and
other T cells destroyed by immunodeficiency.17 Canadian scientists
linked vitamin A deficiency to immuno-incompetence,18 while a
University of California, Davis, team reviewing trial literature found
vitamin A deficiency impairs innate immunity by impeding normal
regeneration of mucosal barriers damaged by infection, and by
diminishing the function of neutrophils, macrophages and NK cells.19
They further noted vitamin A's impact on T helper cells TH2 and TH1
activity.
The vitamin A precursor beta-carotene has shown benefit to the
destructive abilities of NK cells, especially against tumors.20 German
researchers found a diet low in vegetables rich in beta-carotene and
other carotenoids contributes to depressed T cell functioning.21 They
noted tomato juice administration restored T cell function, including
secretion of TH2-like IL-2 and TH1- like IL-4. Dutch researchers
studying plasma levels of six major carotenoids (lycopene, beta- and
alpha-carotenes, beta-cryptoxanthin, lutein and zeaxanthin) in elderly
subjects monitored for upper respiratory infections found high plasma
levels of carotenoids, especially beta-carotene, may lower the
incidence of acute upper respiratory infections.22
As a group, carotenoids can support the immune system by addressing
free radicals, but have also been found to lower occurrence of upper
respiratory infections.23 Individual carotenoids have shown specific
benefits to immune function as both antioxidants and immune
stimulators. Found in high concentrations in tomatoes and tomato
products, lycopene protects immune cells from oxidation.24 Researchers
found supplementation increased plasma carotenoid concentrations and
reduced lymphocyte DNA oxidative damage by half.
Astaxanthin
, typically derived from algae, is another immune stimulator, working
to stimulate lymphocyte proliferation, increase T cell production and
amplify NK cell cytotoxic activity. In separate trials, astaxanthin
administration in mice curbed liver tissue damage and related NK cell
activity,25 and also increased resistance to tumor growth and higher
cytotoxic T-cell and interferon-gamma activity.26
Although best known for its role in eye health, lutein may stimulate
both active and passive immune responses. Animal research shows lutein
supplementation increases lymphocyte proliferation and production of
immunoglobulin G (IgG).27 The most abundant immunoglobulin, IgG enters
the placenta to protect fetuses' pre-immune system development; it
otherwise helps by binding to pathogens and activating the complement,
the fluid of the lymph system. Similar animal study found lutein
supplementation increased T cell CD4 and CD21 lymphocytes as well as
IgG.28 More recently, risk of non-Hodgkin's lymphoma (NHL) was
inversely linked to not only greater intake of vegetables, but also to
higher intake of lutein and zeaxanthin, as well as zinc.29
Zinc helps regulate various immune cells, including T cells, CD4, NK
cells and IL-2. "Zinc is fundamentally one of the most important
nutrients required for immune health-it is involved in over 60 enzyme
systems in the body, many of which are part of the immune system,"
said Paul Dijkstra, executive vice president of InterHealth
Nutraceuticals. "Zinc may not grab the headline attention that newer
discoveries do, but that doesn't diminish its importance."
Michigan State University scientists reported the "immunological
hallmarks" of zinc deficiency are thymus atrophy and compromised
cell- and antibody-mediated response,30 while University of California,
Berkeley, researchers noted even mild zinc deficiency may impact immune
function by decreasing lymphocyte proliferation and the in vitro
secretion of IL-2.31
Researchers studying the mineral's effects on human immunodeficiency
virus (HIV), which uses CD4 for binding, reported zinc status is
essential for T cell division, maturation and differentiation, as well
as lymphocyte response and other immune functions.32 On other illness,
zinc gluconate lozenges (as COLD-EEZE®, from Quigley) lowered the
incidence of the common cold in school children and also reduced use of
antibiotics among the young subjects.33
On zinc's antioxidant contribution to immunity, researchers have
found zinc bound to either L-methionine (as L-OptiZinc®, from
InterHealth) or dl-methionine (as OptiZinc®, from InterHealth)
provided greater antioxidant protection against brain and liver DNA
damage than other forms of zinc tested, including zinc gluconate and
zinc sulfate.34
And unpublished animal research out of North Carolina State University
in Raleigh showed zinc-methionine (as OptiZinc) enhanced
mononuclear-phagocytic function, which is important for disease
resistance and increased cellular immunity.
The presence of minerals, including zinc and copper, is also important
to production of superoxide dismutase (SOD), an endogenous enzyme that
provides various antioxidant protections to cells. SOD coated in a
wheat gliadin layer (as GliSODin™, from P.L. Thomas [PLT]) has been
found to stimulate production of nitric oxide and control production of
superoxide anion by macrophages, helping to modulate immune function by
controlling expression of cytokines and other antioxidant enzymes.35
"Antioxidants, particularly those produced by our bodies-such as
SOD-are vitally important to immunity," said Eric Anderson, brand
manager for PLT. He cited research showing GliSODin as effective in
immune stimulation in HIV patients is based on protection of T cells.
"Apoptosis of T cells is characteristic of HIV and AIDS, and free
radicals contribute to this event," he said, adding consumers not
immune compromised can also benefit from SOD antioxidant protection of
T cells and other immune cells.
Also common in HIV patients, deficiency of the mineral selenium wreaks
havoc on immune function. University of Miami scientists studying the
effects of selenium deficiency on HIV associated selenium levels to T
cell function and apoptosis, noting selenium may enhance resistance to
infection by modulating IL production and Th1 and Th2 response.36
Selenium deficiency may allow invading viruses to mutate and remain for
a longer period in the host, according to research from the University
of North Carolina, Chapel Hill.37 They found selenium-deficient animals
exposed to human influenza virus (flu) experienced more severe and
longer lasting flu, including lung inflammation, than the non-deficient
mice.
Scientists have also logged success with selenium supplementation on
immune response, especially combined with vitamin E, which results in
interactive effects as oxygen radical scavengers, thereby promoting
human lymphocyte response to antigens. 38 Additional research on this
combination therapy showed it enhances the body's response to
bacterial39 and parasitic infections.40
As many of the immune-boosting vitamins and minerals contribute
antioxidant protection, research has focused on the immune benefits of
various other antioxidants, including phytochemicals. Flavonoids are
water-soluble phytochemicals found in plants and noted for antioxidant
benefits and promotion of various immune cells.
Grape seed extract
(GSE) contains numerous flavonoids including proanthocyanidins, which
contribute anti-inflammatory actions and protect mast cells, which
produce histamine. In animal research, GSE proanthocyanidins reduced
UVB-induced increases in immunosuppressive cytokines in the skin, while
enhancing production of immunostimulatory cytokines.41 Additional
animal study revealed GSE can reduce the production of inflammatory
cytokines in an experimental inflammation model.42
Another GSE compound, resveratrol, has been found to modulate several
human immune cell functions related to its effects on cytokine
production by both CD4 and CD8 cells.43 In alveolar (lung) macrophages,
treatment with resveratrol inhibited the release of inflammatory
cytokines in response to outside stimuli.44
Other berries are also rich in immune boosting flavonoids. Cranberry
flavonoids contain anthocyanins and flavonols, and have been found
useful in the immune response to oxidized low-density lipoprotein (LDL)
and its uptake by endothelial macrophages.45 Cranberries and
blueberries have also demonstrated antibacterial properties, especially
in the urinary tract. Cranberry juice has been particularly effective
at preventing E. coli bacteria from adhering to the urinary tract's
endothelial wall,46 a benefit also credited to wild blueberry
proanthocyanidins.47 Cranberry inhibits similar adhesion of
Helicobacter pylori in the gastric wall, a precursor of gastric
ulcer.48 However, a multiple berry extract (as OptiBerry®, from
InterHealth)- cranberry, elderberry, blueberry, raspberry, strawberry
and bilberry-inhibited H. pylori better than individual extracts of
the berries.49
In addition to vitamin C and other nutrients, citrus fruits contain a
wealth of bioflavonoids that are helpful to immune function.
Polymethoxylated flavones (PMFs) are found in the peels of citrus
fruits and are more stable and bioactive, according to SourceOne
Global, supplier of Sytrinol™, a combination of PMFs and tocotrienol
(vitamin E) developed by KGK Synergize. PMFs have shown promise against
inflammatory parameters of immune function. In fact, PMF extract (as
Citri-Z™, from Next Pharmaceuticals) was shown to modulate TNF-alpha
and natural killer cell activity.50
Retailers might find a boost to immune sales by considering popular
antioxidant and flavonoid rich exotic fruits. Açai pulp, from the
berries of an Amazon palm tree, contains a high amount of antioxidants,
as well as beneficial lipids. Research has shown bioactive açai
polyphenols (including anthocyanins) in glycated and aglycone forms
significantly inhibited proliferation of cancer cells (HL-60 leukemia
cells) while promoting apoptosis.51 Lead researcher Steve Talcott,
Ph.D., assistant professor, Food Science and Nutrition, University of
Florida, Gainesville, cautioned these results do not show açai
prevents cancer, but instead show the activity of açai against a
cancerous system. "Compounds that show good activity against cancer
cells in a model system may also have beneficial properties in our
bodies," he stated. "Seven different concentrations were tested
reflecting varying levels of anthocyanins absorbed in the bloodstream
... each group of polyphenolics (glycosides and aglycones) had a
significant impact on reducing the number of live cancer cells
...higher concentrations killed more cancer cells than lower
concentrations."
Planting the Seeds of Immunity
With a complement of bioactive phytochemicals, plants are prominent in
the immune health tool chest. Beyond fruits, numerous herbs contain key
phytochemicals with specific immune activities.
Polysaccharides, complex carbohydrate compounds often found as
structural components of plants, have a dual role in immunity. While
harmful bacteria commonly produce a thick, mucous-like layer of
polysaccharide that cloaks proteins on the surface that would otherwise
provoke immune response, polysaccharides found in numerous herbs have
proven beneficial to immune functions.
Arabinogalactans
, polysaccharides found in the cell walls of vegetables and herbs, have
been shown to enhance NK cytotoxic activity, though the exact mechanism
of action for this effect has not yet been specified.52Echinacea also
contains arabinogalactans, which have been reported to increase
interferon, tumor necrosis factor and IL-1 production through
stimulation of macrophage activity. A study out of Southwest College of
Naturopathic Medicine in Arizona found extracts of E. purpurea and E.
angustifolia combined with larch arabinogalactan, Larix occidentalis,
extract (as ImmunEnhancer AG™, from Lonza Group) increased production
of complement properdin, which is an indicator of immune system
stimulation.53 In fact in vitro research showed E. angustifolia (as
Polinacea®, from Indena) administered to immunocompetent mice infected
with Candida albicans significantly increased survival time and
production of T lymphocytes and interferon.54
A modified Aloe barbadensis polysaccharide (as Active Aloe®, from
Unigen Pharmaceuticals) activated macrophage cells and stimulated
fibroblast growth.55 Acemannan, another polysaccharide in aloe,
activates immune response and has antitumoral activities. A study from
South Korea found immature dendritic cells (accessory cells in
initiating immune response) stimulated with acemannan matured to active
state.56 Similarly, an in vivo study on acemannan (in Manapol®, from
Carrington Laboratories) as an adjuvant in vaccination indicated the
compound increased activation capacity of macrophages.57 And,
researchers from the Medical University of South Carolina, Charleston,
reported in a review article of in vitro and animal studies that
acemannan and complementary beta-1,3 glucans from aloe activate
macrophages and increase the number and function of cytotoxic
T-cells.58
Beta-glucans are also abundant in the cell walls of mushrooms, barley,
oats and yeast. These polysaccharides promote macrophage activity
without over-stimulating cell-mediated immune response. Theories
suggest beta-glucans bind to receptors on macrophages and other white
blood cells, including the receptor dectin-1.59
Yeast-derived beta-1,3/1,6 glucans (as WGP 3-6®, from Biothera) were
found to significantly enhance immune response, as they are taken up by
gastrointestinal macrophages and broken down in the bone marrow to
smaller fragments that could enhance granulocyte activity.60
Researchers reported these enhanced macrophages and neutrophils more
effectively inhibited antigens. Further study revealed administration
of WGP 3-6 to mice enhanced recovery after bone marrow injury,61 and
had the ability to repress transcription of NFkappa-B mediated cytokine
transcription.62
Agaricus blazeii Murill
(ABM), which contains arabinogalactans indicated as crucial to T cell
production and proliferation, also contains beta glucans important to
immune cell cytotoxicity. In an animal model, a tumor cell injected
with Agaricus extract showed regression, according to researchers, who
also noted an activation of macrophages and neutrophils, as well as an
increase in serum levels of immunosuppressive acidic protein.63 Similar
animal research found Agaricus extract exhibited anti-tumor activity
and increased activity of cytotoxic T-cells.64
Ron Steriti, N.D., a private practitioner, reported ABM also fights
cancer with its content of natural steroids, which are different from
chemical steroids that cause cancer. Ergosterol is the main steroid in
ABM that produces the anticancer effect, possibly inhibiting
angiogenesis induced by solid tumors.65
Maitake
mushrooms are rich in beta glucans and have effectively stimulated NK
cell activity via macrophage activation.66,67,68 Also beneficial to T
cell activity, the D-fraction portion of maitake demonstrated antitumor
activities in one in vitro study, decreasing activation of B cells
while activating helper T cells.69 The extract specifically enhanced
production of IFN-gamma, IL-12 and IL-18.
Additional study revealed increased survival of listeria-induced mice
treated with Dfraction, which also experienced increased splenic T cell
activity, with macrophages producing 2.7 times as much IL-1.70 In early
2006, Japanese researchers reported two maitake extracts (as
MaitakeGold 404®, marketed by Tradeworks Group Inc., and Grifron®-Pro
Maitake D, from Maitake Products Inc.) stimulated immune
response-phagocytosis, NK cell activity, expression of surface
markers, cytokine secretion and apoptosis-and exhibited similar or
higher activity than Lentinan (an anticancer drug made from shitake),
while they can also be administered at lower doses and given orally
without loss of activity.71
A variety of medicinal mushrooms contain beta glucans and other
immuneboosting nutrients, lending credence to the popularity of
multiple mushroom supplements. Emma Mann, sales and marketing director
for EcoNugenics, noted Asian doctors use at least 50 species of
mushrooms, some for their inhibition of cancers. She said MycoPhyto®,
a combination of coriolus, reishi, polyporus, Agaricus, cordyceps and
maitake, "acts as an adaptogen, restoring balance to the entire
system and training the immune response as an integrated system against
potential threats." She added these medicinal mushrooms are grown on
a proprietary matrix of immune-supporting herbs and organic brown rice.
"This increases their potency, because mushrooms absorb things from
their environment," she said.
Similarly, a proprietary co-cultivation of organically-grown medicinal
mushrooms, AHCC® (active hexose correlated compound, available in the
United States from Maypro and Quality of Life Labs), protects the
thymus from cell death72 and promotes immune cell proliferation and
cytokine production in the spleen.73 According to a study of Stage IV
cancer patients, AHCC may also increase NK cell activity, and
production of IFN-gamma and IL-12.74 The compound has also shown
benefits in the area of pneumonia, increasing resistance to infection,
decreasing mortality and improving the immune system's ability to
remove related bacteria.75
Infections of the upper respiratory system, including colds, flu and
sinusitis, are among the most common immune challenges consumers face,
especially during the winter months. Complicating immunity against
these infections, the common cold can be any one of hundreds of
rhinovirus strains, the highly contagious flu virus comes in three
types but changes from year-to-year, and sinusitis can be caused by any
number of different bacterial strains or viruses, including cold and
flu strains. In lieu of vaccines, which can be harmful, and
antibiotics, which can be overused to the point of antibiotic resistant
bacteria mutation, various herbs can contribute less invasive
antibacterial and antiviral properties to the immune health arsenal.
Antiviral herbs include: St. John's wort, which is especially
effective against HIV and hepatitis C virus;76elderberry, which
contains ribosome inactivating proteins that might directly counter
viruses, including influenza A and B;77,78licorice, which might
specifically inhibit the SARS and Epstein-Barr viruses;79,80 and green
tea, which has inhibited infections such as influenza, HIV, herpes
simplex type 2 and adenoviruses (respiratory and eye infections).81,82
Green tea's antioxidant flavonoids, namely the catechins, have also
proven beneficial to immune function, enhancing both humoral and
cell-mediated immunity, while lowering risk of cancer and
cardiovascular disease.83 In vitro research shows green tea extract
reduces formation of a marker compound, showing activated cellmediated
immunity;84 while topical application of green tea polyphenols reduces
the risk of UVB light-induced skin disorders associated with immune
suppression.85
The list of antibacterial herbs is even more extensive. One of the most
studied natural antibiotics is garlic, specifically its main
phytochemical allicin, which has been useful against numerous strains
of Staphylococcus epidermis, including antibiotic-resistant strains;86
as well as Aspergillus spp., a mold or fungus that can cause disease.87
Garlic extract is effective against oral bacteria, including
Streptococcus mutans and P. gingivalis, which it can kill on contact.88
In other research, an aqueous extract of garlic inhibited 30 clinically
isolated strains of methicillin-resistant Staphylococcus aureus.89
Often paired with antiviral echinacea, goldenseal and its roster of
alkaloids are effective against numerous bacterial strains-including
S. aureus, Streptococcus sanguis, E. coli and Pseudomonas
aeruginosa90-in addition to inhibiting oral pathogens, including
Streptococcus mutans and Fusobacterium nucleatum.91 Researchers noted
goldenseal's berbine was most effective alkaloid, an assertion
verified by University of Chicago researchers, who showed berberine and
beta-hydrastine both inhibited the growth of H. pylori.92
Echinacea is also paired with Andrographis paniculata and
Eleutherococcus senticosus (Siberian ginseng), a combination that has
proven effective against strains of the common cold.93 Combination
supplementation with Andrographis and Siberian ginseng has also
addressed duration, symptoms and recovery from upper respiratory
infections, including both influenza and sinusitis, common cold,
rhinitis, pharyngitis (sore throat) and nasopharyngitis.94,95,96
Phyotchemical serpentines from both guggul and myrrh gum resins have
demonstrated the ability to curb various bacteria and fungi, including
S. aureus and E. coli, P. aeruginosa, Candida albicans and
salmonella.97,98
Resinous propolis, gathered from trees by bees for anti-infection
protection, can inhibit many bacteria strains including S. mutans,
salmonella, P. aeruginosa, S. sonnei, C. albicans and S. aureus, but
has only a mild effect against E. coli and P. aeruginosa.99,100
Antibacterial mechanisms have also been determined for a few herbs and
spices, including oregano oil and rosemary. Much of oregano's
antimicrobial activity has centered on its phytochemical carvacrol.
Research has shown both oregano and carvacrol inhibit
methicillin-susceptible and -resistant bacteria, including staph
infections (staphylococci).101 However, a 2001 animal study revealed
oregano, but not carvacrol alone, significantly increased survival from
staph infection, indicating either other constituents are to credit or
it is the synergy amongst the oregano phytochemicals.102 Other research
has indicated oregano might damage bacterial cell membranes by
depleting the intracellular pH and ATP concentrations.103
Oregano has also been studied in combination with other antimicrobial
herbs. Oregano, carvacrol, cinnamon leaf, clove and lemon oil were
among herbal remedies indicated as useful against E. coli and S.
enterica.104 Both oregano and rosemary joined basil, cardamom, dill
weed, fennel and parsley as effective herbal treatments against various
bacterial infections, including listeria, staph and Aspergillus.105 On
its own rosemary is considered effective against gram-positive
bacteria, including listeria, staph, S. mutans and B. cereus, and it
slowed the growth of Penicillium Roquefortii.106 Argentine scientists
linked rosemary's antimicrobial activities to its phenolic
composition, with the most effective profile being a methanol extract
containing 30-percent carnosic acid, 16-percent carnosol and 5-percent
rosmarinic acid.107
Mostly used in topical applications, tea tree oil not only halts
bacteria and yeast common to ear infections,108 but it also targets
oral cavity pathogens, including P. gingivalis, F. nucleatum, S.
mutans, S. sobrinus and A. actinomycetemcomitans.109
A non-herbal antibacterial source, probiotics produce bactericidins,
defensins, cationic proteins and lactoferrin, all of which work to
destroy other bacteria that compete for a hold in the body. Scientists
have reported probiotic lactic acid bacteria signal the immune system
through innate cell surface pattern receptors or by activating lymphoid
cells (as found in the Peyer's patches).110 Bifidum has also
displayed effectiveness in increasing proportions of total, helper and
activated T lymphocytes and NK cells.111 Various strains of
lactobacilli and bifidum probiotics have inhibited harmful bacteria,
including salmonella,112 by stimulating IgA and IgM.113,114
Preliminary research revealed subjects exposed to a yeast culture (as
Epicor™, from Embria Health Sciences) had decreased CD8 cells and
immune complexes, as well as increased NK cell activity, salivary IgA
and glutathione RBC; inhibition of E. Coli and Candida was also found.
Immunoglubulins are glyoproteins that function as antibodies.
Colostrum, the first milk produced from mammals following birth, is a
rich source of natural immunoglobulins. The U.S. Department of
Agriculture (USDA) explained a wide array of humoral and cellular
immune mechanisms are present in the mammary gland and actively
participate in providing immunity to newborns.115
According to various research reports, bovine colostrum concentrate
taken orally increases immunoglobulins, specifically IgA, in the face
of a bacterial challenge, such as from salmonella.116 Additional
research showed bovine colostrum supplementation activates leukocyte
phagocytosis.117
Purified bovine serum also delivers natural immunoglobulins, improving
immune function and fighting bacterial infections.118 Orally
administered bovine serum (as ImmunoLin™, from Proliant) can enhance
the animals' recovery from infection, as well as modulate the
production of inflammatory cytokines.119
There is always a new, bold malady to challenge the human immune
system, but the natural products industry is equally fresh with new
products. In response, retailers are educating themselves and their
customers about the immune system and all the different researched
mechanisms by which vitamins, minerals, herbs and specialty compounds
can boost immunity and help temper illnesses, including bacterial and
viral infections.
Triple AAA Alert: Autoimmune, Allergies and Asthma
Sometimes the human immune system malfunctions, initiating an immune
response to a substance it misidentifies as a pathogen. These cases can
be tricky to approach. Noel Rose, M.D., Ph.D., a professor of pathology
at Johns Hopkins, pointed out the possibility that treatments altering
the immune system's overall function could make one autoimmune
disease better, but make a second one worse.
Most often, the triggered response involves a fair amount of
inflammation, resulting in pain, discomfort and reduced organ or body
functioning. Fatty acids and their metabolism in the body play major
roles in the immunes system's inflammation management system.
A National Institute on Aging study found serum polyunsaturated fatty
acids (PUFAs), especially total omega-3 fatty acids, were independently
associated with lower levels of pro-inflammatory markers and higher
levels of anti-inflammatory markers, independent of confounders;1 this
supports the notion that omega-3 fatty acids may be beneficial in
patients affected by autoimmune diseases characterized by active
inflammation.
Conjugated linoleic acid
(CLA) has also proven useful in autoimmunity marked by inflammation. A
study in healthy men reported CLA enhanced humoral antibody production
in response to a vaccination challenge without affecting cellular
immune response.2 A follow-up study investigating CLA on production of
antibodies and inflammatory cytokines without immune challenge found
supplementation increased IgA and IgM, while decreasing IgE, which is
linked to allergic response; the level of proinflammatory cytokines was
also decreased.3
Excessive oxidative stress is thought to have an important role in the
pathogenesis of autoimmune diseases by enhancing inflammation, inducing
apoptotic cell death and breaking down the immunological tolerance.
According to a clinical review, French maritime pine bark extract (as
Pycnogenol®, distributed by Natural Health Science) acts as an
antioxidant, and demonstrates anti-inflammatory activity and
immunomodulatory effects in human and animal studies of autoimmune
conditions, such as lupus and asthma.4 In fact, Pycnogenol has been
shown to block the activation of nuclear factor kappa-B cells involved
in pro-inflammatory cytokine expression5 and to inhibit the release of
histamine from mast cells.6 Researchers at the University of Arizona,
Tucson, found patients with chronic asthma given 1 mg/lb/d of
Pycnogenol responded favorably to treatment and had significantly
reduced serum leukotrienes.7
Herbs are also effective against allergies. A blend of seven herbal
extracts (as Aller-7®, from InterHealth), has been studied for its
impact on immune function and ability to modulate mast cell reactions.
A multi-center clinical trial showed 12 weeks of Aller-7
supplementation improved symptoms by between 40 to 100 percent in 94
percent of patients in open label trials and 92 percent of patients in
double blind, placebo-controlled trials.8
-------------------------------------------------------------------
While Cristina may not be able to try to affect her genetic pathway
with
food. There isn't anything stoPPing all of us. Then again till all the
psoriasis
genes and their working have been delineated neither Cristina or all
psoriatics
will know the truth.
randall...time to eat suPPlements? Good foods?
randall
P news from around the world.
Big day for the NPF and you.
http://biz.yahoo.com/prnews/060801/sftu131.html?.v=42
Press Release Source: The National Psoriasis Foundation
U.S. Senate Passes Psoriasis Resolution Calling for Improved Research
and Access to Care
Tuesday August 1, 2:49 pm ET
PORTLAND, Ore., Aug. 1 /PRNewswire/ -- The U.S. Senate passed Senate
Resolution 420 (S. Res. 420), a bipartisan resolution calling for
improvements in treatment and access to care for individuals with
psoriasis and psoriatic arthritis. Sen. Gordon Smith, R-Ore., lead
sponsor of the resolution, is a dedicated champion for the psoriasis
community and worked to ensure passage of the measure prior to
Psoriasis Awareness Month in August.
Sen. Frank Lautenberg, D-N.J., joined Smith in leading the effort; they
were supported by Sens. Tim Johnson, D-S.D., Robert Menendez, D-N.J.,
Rick Santorum, R-Pa., John Warner, R-Va., and Ron Wyden, D-Ore.
The resolution recognizes that psoriasis and psoriatic arthritis can be
painful, debilitating diseases that can significantly and adversely
impact quality of life. Millions of people hold misconceptions about
psoriasis, and it remains an often misunderstood disease. The
resolution draws much-needed attention to the seriousness of psoriasis,
the importance of early diagnosis and proper treatment, and the need
for public awareness about psoriasis.
Through passage of the resolution, the U.S. Senate is encouraging the
federal government to expand its psoriasis research efforts, including
the psychological and physical effects of the disease. The Senate
resolution also supports efforts to increase access to treatments for
individuals living with psoriasis and psoriatic arthritis. The National
Psoriasis Foundation will work with members of Congress and federal
research agencies to ensure that the intent of the resolution is
carried out.
"The National Psoriasis Foundation applauds today's Senate passage of
an important resolution seeking to improve psoriasis research and
access to care," said Gail M. Zimmerman, president and CEO of the
National Psoriasis Foundation. "According to the National Institutes of
Health, as many as 7.5 million Americans live with psoriasis. Thanks to
the leadership of Senators Smith and Lautenberg, the need to boost
psoriasis research and access to care has been elevated at the highest
level of government."
Passage of S. Res. 420 is part of a comprehensive federal legislative
agenda being pursued in Washington, D.C., by the Psoriasis Foundation.
The Psoriasis Foundation is also advocating passage of a resolution in
the House of Representatives that is similar to the Senate resolution.
The House resolution (H. Con. Res. 340) urges expansion of genetic,
clinical and basic research focused on increasing understanding of the
causes of psoriasis and psoriatic arthritis. It also calls for the
Secretary of Health and Human Services to convene a special panel to
study the availability of treatments for individuals with psoriasis and
psoriatic arthritis.
(((((((((((((((((((((((((((((((((((((((((((((((())))))))))))))))))))))))))))))))))))))))))))))))))))))))))
Big Days for me. lol
I started taking ALCAR for its longevity potential recently. About the
same time
my P which was clearing to very low levels anyway, continued to get
clearer. A nice surPrise as i've been taking out suPPlements right and
left
to try and get down to the essentials. I may have found it. If the IP6
isn't
it or the dozen or so other supplements, then what was helping?
An ALCAR search led me to this next link.
http://groups.google.com/groups/search?q=hsp60+T-cells+kofi&qt_s=Search
Looked good to me.
So what are heat shock proteins? Am I full of them now?
What else can they help out with?
http://www.antigenics.com/products/tech/hsp/
& in action,
http://www.antigenics.com/products/tech/hsp/animation.html
This looks interesting. Let say that psoriatics have good metabolism.
So good that the garbage doesn't all get taken out and this sorta
explains why starvation seems to help with lowering psoriasis.
Isn't it the P53 gene that kicks in with starvation?
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=p53+starvation
Are the chaperones working, but not enough of them?
Then what? Is the skin cheated by a lack of heat shock proteins? l
Says we need more heat shock proteins!
We've gone over this quite a few times now,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=heat+shock+proteins&
Exercise and vitamin C with ALCAR seems to be a good bet.
Does IP6 help out in this regard? Time will tell.
_________________________________________________________
Here's a new term i'm completely unfamiliar with.
Nitrosoperoxycarbonate
WE psoriatics have problems with iNOS and NO. Is this one gonna be
called NOPC?
NOPE. It's called Onooco2,
http://en.wikipedia.org/wiki/Peroxynitrite
http://www.scenta.co.uk/scenta/news.cfm?cit_id=997466&FAArea1=widgets.content_view_1
New research may help scientists better understand the chemical
associations between chronic inflammation and diseases such as cancer
and atherosclerosis.
Link between inflammation and disease explored
The work could lead to drugs that break the link between the two.
When an infection occurs, immune cells flock to the area and secrete
large amounts of highly reactive chemicals to combat the invader.
But these inflammatory chemicals also attack normal tissue surrounding
the infection and damage critical components of cells, including DNA.
During chronic inflammation, the damage may lead to mutations or cell
death and even to cancer and other diseases.
Researchers from the Massachusetts Institute of Technology (MIT) have
discovered that the DNA damage produced by one of these inflammatory
chemicals, nitrosoperoxycarbonate, occurs at unexpected locations along
the DNA helix.
The finding counters the prevailing theory about where the DNA damage
occurs and may shed light on new ways to diagnose and combat
inflammation.
"We need to understand the mechanisms of inflammation in order to make
new drugs that will break the link between inflammation and disease and
to develop predictive biomarkers," said Dr Peter Dedon, professor of
toxicology and biological engineering and associate director of the
Biological Engineering Division at MIT.
"One of our goals is to develop biomarkers that can tell if you have
inflammation and to define its extent, severity and location."
For years researchers have studied how the chemicals associated with
the body's response to infection can damage DNA.
The process begins with the removal of an electron from guanine, one of
the four base building blocks that determine the genetic code in DNA.
The removal process is called oxidation, and guanine is the most easily
oxidised of the four building blocks.
The prevailing theory has been that oxidation occurs most frequently
when the guanine is sandwiched between two other guanine bases in the
DNA helix.
By using comprehensive chemical screening and analysis of the frequency
of DNA damage, the researchers found that a chemical produced during
inflammation, nitrosoperoxycarbonate, actually caused oxidative damage
at guanines that were supposed to be the least easily oxidised.
The damage did not occur in clusters of guanine as expected, but rather
at locations where guanine precedes cytosine, another of the four
building blocks.
"That observation overturns the prevailing theory for predicting the
location of DNA damage in the genome and complicates our understanding
of the basis for diseases arising from chronic inflammation," said
Dedon.
"But it is likely to stir up discussions in the DNA damage and
mutagenesis fields that could help us better understand the
consequences of inflammation."
The findings were reported in a recent advance online issue of Nature
Chemical Biology.
---------------------------------------------------
This next article is basically the same thing as above. But has a good
illustration.
http://www.physorg.com/news73058892.html
&
http://www.physorg.com/newman/gfx/news/dna-damage-image-enlarged.jpg
Hey! LOOK at the LPS rushing in to cause inflammation!
Are we full of it or not? Drink a little booze and it creeps in thru
those leaky gut walls. <w>
[...]
Alcohol induces mucosal injury in the upper gastrointestinal tract and
leads to marked increase in the permeability of the gut mucosa to
macromolecules such as endotoxin. The resulting endotoxemia then leads
to activation of Kupffer cells and other macrophages. The increased
release of pro-inflammatory mediators (e.g., TNF-alpha, Il-1, reacting
oxygen species) and infiltration of other inflammatory cells (e.g.,
neutrophils) finally causes liver damage.
<sniP>
Let's find out about the biological effects of peroxynitrite and
related nitrogen species.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16752428&query_hl=10&itool=pubmed_docsum
What can you do? Keep eating the brown mustard....
OR
How about a brown mustard and curcumin topical?
That hot dog is gonna clear fast. LOL
randall... where do I come uP with this stuff!.... Online stuPide!
randall
Another slow day for P News. I'll try to dress it uP.
You've seen those Da'iry commercials yet? These calcium challenged
outer space
aliens come to earth to find the wonder tonic (got milk?) and then
can't figure
out how to extract the tonic from da iry the supreme one.
A message from the emPeror of brittlelactia,
http://www.planetinneed.com/
No wonder milk prices are going uP! How much does one pay actors
from other star systems? Can't be chicken feed. lol
How many psoriatics do better with LESS dairy? I seem to. Seeing
as how sterile wonder tonic was prescribed by Doctor Spock,
http://www.andrew.cmu.edu/user/bpantano/spock.jpg
Whoops. Wrong spock?
OK,
http://www.cnn.com/US/9803/16/obit.dr.spock/
Could the suPreme one for spaced out psoriatics be a GOAT?
http://wtimg.us.publicus.com/apps/pbcsi.dll/bilde?Site=WT&Date=20060803&Category=NEWS&ArtNo=608030847&Ref=AR&Profile=1116&title=1&MaxW=425&MaxH=500
http://www.telegram.com/apps/pbcs.dll/article?AID=/20060803/NEWS/608030847/1116
[...]
Cambridge-based Merrimack Pharmaceuticals Inc. has been testing a form
of human alpha-fetoprotein, which was made in GTC goats, in patients
with rheumatoid arthritis and psoriasis.
"They're the first people to get a transgenically produced protein
(approved)," said Philip M. Nadeau, a director and senior research
analyst for Cowen and Co. who rates GTC shares "outperform." "I
think that's the real significance here. There's historically been
people who said it would never happen, the regulatory authorities, for
whatever reason, would never approve a transgenic drug."
<sniP>
----------------------------------------
Has our Goat finally come in?
Get your light sabers ready for this next one. Laser war in
psor country.
-----------------------------------
http://home.businesswire.com/portal/site/google/index.jsp?ndmViewId=news_view&newsId=20060803005208&newsLang=en
Ra Medical Systems Sues PhotoMedex
CARLSBAD, Calif.--(BUSINESS WIRE)--Aug. 3, 2006--Ra Medical Systems,
Inc. announced today that it has sued PhotoMedex, Inc. (NASDAQ: PHMD)
for manufacturing and selling lasers in California without a
manufacturing license and for unfair competition based on Medical
Practices Act violations.
Commenting on the lawsuit, Dean Irwin, President of Ra Medical Systems,
said, "We have learned through direct testimony and by the notice of
violation from the State of California provided by PhotoMedex that they
have been operating without a license, in violation of the law. We were
surprised to learn that they did not have the required license as they
had recently accused us of the same thing."
The unfair competition claims arise from PhotoMedex's practice of
contractually limiting the tools that physicians may use to treat
patients, specifically prohibiting the use of excimer light sources
other than PhotoMedex's equipment.
In court documents filed just days ago, their defense included the
admission that physicians are free to use any type of excimer light
equipment, and that the practical remedy should they do so, is that
PhotoMedex will simply remove its own equipment. "While it always
appeared that this was the practical remedy against physicians who
chose another excimer light source, the admission by PhotoMedex in its
court papers makes it abundantly clear," commented Tracy Nation,
attorney for Ra Medical Systems. Ms. Nation has successfully defended
Ra Medical Systems against PhotoMedex's trade secret claims, as well as
the more recent patent-in-suit claims.
Ra Medical Systems, Inc., a privately held medical device company was
founded in 2002 to commercialize excimer laser phototherapy. Based in
Carlsbad, CA, the company manufactures and markets an advanced excimer
laser system, the EX-308, for the treatment of skin diseases including
psoriasis and vitiligo.
This media release may contain forward-looking statements that
constitute Ra Medical Systems' current intentions, hopes, beliefs,
expectations or predictions of the future, which are therefore
inherently subject to risks and uncertainties. For additional
information on factors that could affect Ra Medical's performance,
please call the company directly. Ra Medical Systems expressly
disclaims any obligations or undertaking to release publicly any
updates or revisions to any such statements to reflect any change in Ra
Medical Systems' expectations or any change in events, conditions, or
circumstances on which any such statement is based.
----------------------------------------------------
randall... ho hum, did a bum get your goat?
randall
P News from around the world.
>From the Oregonian,
http://www.oregonlive.com/news/oregonian/index.ssf?/base/news/11546547715210.xml&coll=7
Psoriasis conference offers news, support for sufferers
Health - Officials will launch a "Finding a Cure" campaign at the
annual meeting
Friday, August 04, 2006
ANDY DWORKIN
Hundreds of people with psoriasis are in Portland this weekend to
discuss their disease and learn about a project that will help explore
its root causes.
About 300 people are expected at the annual meeting of the National
Psoriasis Foundation, which is based in Portland, said Paula Fasano,
the nonprofit's marketing and communications director.
She said the patient-focused meeting offers "an opportunity for people
with psoriasis to come and learn about new treatments, to talk to
medical professionals and to discuss some of the emotional components."
The emotional hurt of psoriasis is fueled by a lack of understanding of
the disease, which leaves sufferers with patches of red, scaly skin and
sometimes blisters or arthritis. Many people think it is a contagious
rash and avoid contact with psoriasis sufferers.
"We get calls all summer from people who are kicked out of community
pools, kicked out of water parks" because people fear the illness can
spread, Fasano said.
In fact, psoriasis does not spread through contact. It is a disorder
linked to problems in the immune system that appears to have a strong
genetic component.
The foundation will publicly start a $5 million "Finding a Cure"
campaign at the conference. The money will pay for more studies on the
disease's biology and help the group lobby for more funding and better
patient care. The group already has a $1 million pledge to help create
a new bank of blood samples, the fundraising effort's centerpiece.
The bank will store blood samples from people with and without
psoriasis, so scientists can search for key differences, and keep years
of records about patients' symptoms and treatments. Researchers can
apply to use those materials to see how biological information held in
the blood ties to their progress. In 1994, the foundation started a
tissue bank, which helped make the first genetic link to psoriasis.
Three genes have now been linked to the disease.
The meeting runs from 3 p.m. today through 11 a.m. Sunday at the
Portland Marriott Downtown Waterfront. Registration costs $115, or $95
for foundation members. For more information, go online to
www.psoriasis.org/events or phone 503-244-7404.
Andy Dworkin: 503-221-8239; andyd...@news.oregonian.com
------------------------------------------------------------------------
Don't you want to get on over to Portland and take it all in?
I do. I went to one of these NPF events a few years back. It was a
total P/life experience.
Nice people full of hoPe and fun to relate with.
They had booths set up for all the vendors and take em or leave em,
they
were interesting to BS with as well.
Of course the NPF folks were all over the place and you could
participate
in various programs designed to give you hands on face to face time
with them. Putting faces to names helps to humanize the process.
And how do you know that someone really wants to help if you
don't/can't
look them in the eye?
---------------------------------------------------------
Speaking of eye's and truth.
http://www.pantheon.org/areas/gallery/mythology/africa/egyptian/horus.gif
I was hanging around the NPF forum last week. My Rx to get in touch
with you know what.
In response to all the arguing between the diet versus the
biological/drug folks,
I started working on a post. While doing that I continued to read the
thread.
It didn't seem right to post it and so i waited for the right time that
never came.
They have moderator's over there that can lock up a post when folks go
ballistic.
The moderator can simply delete posts they don't like or have to many
ad hominem attacks.
My critical rebuttal-ish post didn't feel right to be posted after
awhile.
THEN,
The thread was locked.
Sticking my post it in a different thread, like i'd usually do, didn't
cut the mustard for some reason.
So here it is.
----------------------------------------------
Subject: P post for a hot thread (npf forum)
-----------------
Hey?
Where did all those folks with a vested interest in their P truth
go? <g>
Who wants to play in their thread now? The moderator shut
it down. lol
Go find a new thread?
Are we having the alts versus the allo's fight in this little corner of
P forums?
I missed to many posts before the moderator dismissed it
and deleted the offending posts! Are we back in grade school. LOL
Let's frame it. So we sorta know whose on what side.
Alt stands for alternative and allo for allopathic.
http://en.wikipedia.org/wiki/Allopathic_medicine
The allo's actually prefer to refer to themselves as evidence based
medicine (EBM).
http://ebm.bmjjournals.com/
Who can blame them? To let some under educated alt define you isn't
exactly flattering. They didn't get thru med school. Why suffer their
nom de guerre?
And furthermore they are genetically inferior educationally wise or
they'd
be able to handle real evidence based medicine, like the allo's.
Why would an allo even hang here?
Most psors won't or can't even translate their language.
More reason for you to think their out to screw you with their
BIG PHARMA drugs.
So.
Go to your room you bad posters!
And learn to play right!
Treat each others fairly.
You have to behave in the real world?
What a crack uP.
Being stuck in your position (world view) isn't exactly showing respect
to
those in oPPosition. You may feel you have them beat,
but then they beat you uP with their crap. Are we confused yet? lol
Let's all get along. Or was that, "can't we all get along"? (rodney
king)
Where does TNF come from? And why do psoriatics
have so much? The more TNF-a you have the worse the
severity right?
Ah yes.
If on a scale of 1 to 10 psoriatics have 5++++ levels
of TNF, then regular folks may be around 1-3.
But whats the need for high levels and why won't it shut off?
First, taking a biological (enbrel etc.) to block the excess TNF
doesn't
really make you all that much more susceptible to cancer
and other aliments. But if you have TB it needs to be
watched by your derm. There are instances when you
need all the TNF you've got. Your derms know that. Most folks with
cancer
would benefit from your excess levels! If only you
could plug yourself in to them and get paid for it!
All of us Th1 psoriatics would be rich. lol
I myself could eat crap food around the clock and get
RICH off my excess levels of TNF-a. LOL
(So diet is imPortant? Didn't you read my arachidonic acid thread? See!
Most won't take the time to understand their own condition)
Let's learn something. That's why EBM is imPortant. To know if nothing
else.
http://en.wikipedia.org/wiki/Tumor_necrosis_factor
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191160
How'd they find it? They injected mice with endotoxin (LPS) and
it just showed uP? Hallelujah!
Can I have an Amen?
Amen!
Yet, it came from lymph cells it says.
And the wikipedia says it came from macrophages. (white blood cells)
http://en.wikipedia.org/wiki/Macrophage
This is a fairy tale about adiposity and TNF, not craPPy genes
that go bumP in the night! Or is it?
The BIG MAC's aren't bad, they eat the crap in your blood.
But how much crap are we full of, to get really high levels of TNF?
If your a 10 on the TNF scale, your PASi is looking really bad, right?
YeP! Your like covered in P! Yucky! dude!
So high in fact that the more TNF the more P, should you have the
psoriasis genes.
Lets follow the fat facts for inflammation near and dear to our hearts
and skin.
http://www.lipidsonline.org/slides/slide01.cfm?tk=18&dpg=1
Slides 22 to 28 start to get to the meat of this problem.
Lets go back to a couple of illustrations created by Folks
who have worked directly with the NPF, Dr.'s Krueger and
Bowcock, (Bowcock being the tissue bank- geneticist from the early
90's)
http://ard.bmjjournals.com/content/vol64/suppl_2/images/large/ar31120.f1.jpeg
http://ard.bmjjournals.com/content/vol64/suppl_2/images/large/ar31120.f2.jpeg
To start to GET the P genetic's from Krueger/Bowcock's paper,
http://ard.bmjjournals.com/cgi/content/full/64/suppl_2/ii30
Where do these iDC's (immature dendritic cells) come from?
An antigen poPs uP and they just go in to action? Or called in to
action so to sPeak?
http://www.sri.com/biosciences/infect/basic.html
The antigen for p is the trigger or was, but then it fades from view
and the autoimmune (now called I.M.I.D)
http://www.medicalnewstoday.com/medicalnews.php?newsid=11029
process takes over. Why?
The $64B question.
IMO the LPS (endotoxins) keep us skewed towards the Th1 side of things
as opposed to the Th2 side indicative of diseases like cancer.Though
with enough meds you can have both and is an example of a iatrogenic
condition.
But medicine has recognized that inflammation, CHD (chronic heart
disease) and
diabetes are all connected. Surely diet is one cure, but all doctors
know how
many of their patients have the patience to stick with that. So meds
pick uP
the slack,
http://www.expresspharmaonline.com/20060731/market04.shtml
T Helper One cells (Th1) are indicative of autoimmune conditions as the
cytokines (like TNF, IFn, NF-Kappa-B etc) are driving the skewed immune
system.
http://inet.uni2.dk/~iirrh/IIR/03Th/Th.htm
After viewing the above lipidsonline slide show, the question that PoPs
uP for myself is whether psoriasis is compensatory for heart disease?
With all the tnf and lipids why don't our arteries simply clog up and
kill us?
APParently our P genes and HDL's keep us from biting the bullet sooner
then we'd hoPe anyway? Who knows? Without knowing the etiology for P we
simply don't have the answers.
New ones show uP daily in pubmed abstracts,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16865225&query_hl=5&itool=pubmed_docsum
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16617159&query_hl=5&itool=pubmed_docsum
Is Ptx-3 the missing piece? To early to tell most likely.
So, why does this scaly inflammation choose to end up in the skin?
Think about that. The skin is another organ of elimination, could the
LPS (endotoxins) simply be pushed in that direction to detox the body?
Like with lipofuscin
and aging?
http://en.wikipedia.org/wiki/Lipofuscin
The alts have been all over that deal from day 1. Yet most folks
know their diets aren't worse then most other folks who don't have
psoriasis and that ends their argument.
Once psoriasis is out there (skin) the inflammation is treated like a
wound but is continually fueled from inside the system? Systemic LPS
infection? Or does
permeable skin allow for iNOS and NO pathways brought under control
with
occlusion and drugs?
Why isn't the body taking the time to make lipid binding protein (LBP)
to capture and process the LPS naturally?
http://www.biochemsoctrans.org/bst/031/0785/0310785.pdf
&
http://genome.jouy.inra.fr/sakei-prot/reader/ProteinPanel?source_id=LSA&protein_id=1114&locus_tag=LSA1114
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11347890&dopt=Abstract
Maybe a lack of LBP's is one of our genetic problems?
Or the kupffer cells aren't clearing complement,
http://en.wikipedia.org/wiki/Kupffer_cell
Are they overtaxed?
Time will tell.
randall.. and so will I
---------------------------------------------
That last part isn't clear enough for me. It seems the more I clear the
clearer
my P truths become to me. As i've been doing a little trial with ALCAR
the last few months reality and the knowledge behind it are clearer.
lol
The reason i didn't post the above was contained in the post. Why
bother when
some of those psoriatics are haPPier fighting in the mud puddle?
Their life meaning tied to their purism,
http://en.wikipedia.org/wiki/Purist
WE don't have that here in this group. <w>
WE can even talk religion and politics without having to be moderated.
randall... i suPPose time is riPe for confabulation!
randall
Yesterday it was goat milk. Today try bison milk from the UK,
http://www.timesonline.co.uk/article/0,,8126-2298194,00.html
[...]
The subject of whether buffalo milk is healthier than cow’s milk is
murkier. There is some anecdotal evidence that people suffering from
cow’s milk intolerance — with eczema, psoriasis and digestive
allergic reactions — can drink buffalo milk because it has a
different protein make-up. “It can be frustrating if you can’t
drink milk or use it in cooking,” says Lindsey McManus, for the
charity Allergy UK. “For people with mild intolerance my advice would
be to try it and see. But I wouldn’t recommend it to anyone with a
serious milk allergy; it’s not worth the risk.” <sniP>
----------------------------------------------------------------------------------
Of mice and men with P.
Thank God for these P TEST mice.
The answers to P and us will be getting clearer in the process. Or so
we hoPe!
Today we have three new abstracts, a troika of BIG MAC (macrophage)
attacks and their influence on P.
Lets review macrophages and P real quickly.
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=macrophages
See figure 4 for mac's in the scheme of things,
http://www.medscape.com/content/2002/00/43/65/436533/436533_fig.html
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16886055&query_hl=2&itool=pubmed_docsum
Misbehaving macrophages in the pathogenesis of psoriasis.
* Clark RA,
* Kupper TS.
Harvard Skin Disease Research Center and Department of Dermatology,
Brigham and Women's Hospital, Boston, Massachusetts, USA.
Psoriasis is a chronic inflammatory skin disease unique to humans. In
this issue of the JCI, 2 studies of very different mouse models of
psoriasis both report that macrophages play a key role in inducing
psoriasis-like skin disease. Psoriasis is clearly a polygenic,
inherited disease of uncontrolled cutaneous inflammation. The debate
that currently rages in the field is whether psoriasis is a disease of
autoreactive T cells or whether it reflects an intrinsic defect within
the skin - or both. However, these questions have proven difficult to
dissect using molecular genetic tools. In the current studies, the
authors have used 2 different animal models to address the role of
macrophages in disease pathogenesis: Wang et al. use a mouse model in
which inflammation is T cell dependent, whereas the model used by
Stratis et al. is T cell independent (see the related articles
beginning on pages 2105 and 2094, respectively). Strikingly, both
groups report an important contribution by macrophages, implying that
macrophages can contribute to both epithelial-based and T cell-mediated
pathways of inflammation.
PMID: 16886055
Polygenic? That means like more then one? LOL
CraP! Just our luck. Watch it be six or seven of them. Whew...
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16886059&query_hl=2&itool=pubmed_docsum
Activated macrophages are essential in a murine model for T
cell-mediated chronic psoriasiform skin inflammation.
* Wang H,
* Peters T,
* Kess D,
* Sindrilaru A,
* Oreshkova T,
* Van Rooijen N,
* Stratis A,
* Renkl AC,
* Sunderkotter C,
* Wlaschek M,
* Haase I,
* Scharffetter-Kochanek K.
Department of Dermatology and Allergic Diseases, University of Ulm,
Ulm, Germany. Department of Cell Biology, Free University, Amsterdam,
The Netherlands. Department of Dermatology and Center for Molecular
Medicine, University of Cologne (CMMC), Cologne, Germany.
The CD18 hypomorphic (CD18(hypo)) PL/J mouse model clinically
resembling human psoriasis is characterized by reduced expression of
the common chain of beta(2) integrins (CD11/CD18) to only 2-16% of WT
levels. Previously we found that this chronic psoriasiform skin
inflammation also depends on the presence of CD4(+) T cells. Herein we
investigated the role of macrophages in this CD18(hypo) mouse model.
Activated macrophages were significantly increased in lesional skin as
well as in inflamed skin draining lymph nodes (DLNs) of affected
CD18(hypo) mice and were identified as being an important source of
TNF-alpha in vivo. Both depletion of macrophages and neutralization of
TNF-alpha resulted in a significant alleviation of psoriasiform skin
inflammation. As monocyte chemotactic protein 1 was enhanced in
lesional skin of affected CD18(hypo) mice, we intradermally injected
recombinant murine monocyte chemotactic protein-1 (rJE/MCP-1) alone or
in combination with rTNF-alpha into the skin of healthy CD18(hypo)
mice. Only simultaneous injection of rJE/MCP-1 and rTNF-alpha, but
neither substance alone, resulted in the induction of psoriasiform skin
inflammation around the injection sites with recruitment and activation
of macrophages. Collectively, our data suggest that maintenance of
psoriasiform skin inflammation critically depends on efficient
recruitment and activation of macrophages with sufficient release of
TNF-alpha.
PMID: 16886059
Here is the Stratis abstract, mentioned by the first abstract.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16886058
Pathogenic role for skin macrophages in a mouse model of
keratinocyte-induced psoriasis-like skin inflammation.
* Stratis A,
* Pasparakis M,
* Rupec RA,
* Markur D,
* Hartmann K,
* Scharffetter-Kochanek K,
* Peters T,
* van Rooijen N,
* Krieg T,
* Haase I.
Department of Dermatology and Center for Molecular Medicine, University
of Cologne (CMMC), Cologne, Germany. European Molecular Biology
Laboratory, Mouse Biology Unit, Monterotondo, Italy. Institute for
Genetics, University of Cologne, Cologne, Germany. Department of
Dermatology, University of Munich, Munich, Germany. Department of
Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
Department of Cell Biology, Free University, Amsterdam, The
Netherlands.
Psoriasis is a common skin disease, the pathogenesis of which has not
yet been resolved. In mice, epidermis-specific deletion of inhibitor of
NF-kappaB (IkappaB) kinase 2 (IKK2) results in a skin phenotype that
mimics human psoriasis in several aspects. Like psoriasis, this skin
disease shows pronounced improvement when mice are treated with a
TNF-neutralizing agent. We have found previously that this phenotype
does not depend on the presence of alphabeta T lymphocytes. In order to
evaluate contributions of other immune cell populations to the skin
disease, we selectively eliminated macrophages and granulocytes from
the skin of mice with epidermis-specific deletion of IKK2
(K14-Cre-IKK2(fl/fl) mice). Elimination of skin macrophages by
subcutaneous injection of clodronate liposomes was accompanied by
inhibition of granulocyte migration into the skin and resulted in a
dramatic attenuation of psoriasis-like skin changes. The
hyperproliferative, inflammatory skin disease in K14-Cre-IKK2(fl/fl)
mice was a direct consequence of the presence of macrophages in the
skin, as targeted deletion of CD18, which prevented accumulation of
granulocytes but not macrophages, did not lead to major changes in the
phenotype. Targeted deletion of the receptor for IFN-gamma revealed
that the pathogenesis of the skin disease does not depend on classical
IFN-gamma-mediated macrophage activation. Our results demonstrate that
in mice epidermal keratinocytes can initiate a hyperproliferative,
inflammatory, IFN-gamma-independent, psoriasis-like skin disease whose
development requires essential contributions from skin macrophages but
not from granulocytes or alphabeta T lymphocytes.
PMID: 16886058
If the really real scientist are going back to look at macrophages,
can't
they look at endotoxin (LPS) in the process?
===============================================
What can one a psoriatic do?
I take suPPlements aimed at different areas and pathways that I figure
the psoriasis pathophysiology is hooked up with, (polygenetically
speaking of course) <w>
http://en.wikipedia.org/wiki/Pathophysiology
Here are some new and old ones from a company i'm looking at,
http://www.vrp.com/art/1181.asp
Super duper gluathione article frm vrp....
HA from vrp,
http://www.vrp.com/art/1210.asp
Got CFS? Take epicor,
http://www.vrp.com/art/1923.asp
&
http://www.vrp.com/art/1925.asp
-----------------------------------------------
Time to review the villians in immunity.
http://innateimmunity.net/IIPGA2/PGAs/InnateImmunity/biological_significance
Biological Significance
http://groups.google.com/groups/search?q=cd14+psoriasis&qt_s=Search
CD14
CD14 was the first pattern recognition receptor to be identified. CD14
is expressed on, and secreted by, myeloid cells. CD14-negative cells,
such as epithelial and endothelial cells, become responsive to
bacterial pathogens in the presence of soluble CD14 (sCD14), a protein
present in the serum in microgram amounts and secreted by monocytes and
the liver. Membrane-bound and sCD14 bind a variety of bacterial
products, e.g., LPS from Gram-negative bacteria, lipoteichoic acids
from Gram-positive bacteria, mycobacterial glycolipids, and mannans
from yeast s. Responses of inflammatory cells to subpicomolar
concentrations of bacterial ligands require LPS-binding protein (LBP),
a lipid transfer protein that recognizes the lipid A moiety of LPS and
facilitates the binding of LPS to sCD14 or membrane CD14. At the
molecular level, CD14 acts by transferring LPS and other bacterial
ligands from circulating LPS-binding protein to the Toll-like receptor
4/MD-2 signaling complex. Engagement of this complex results in the
activation of innate host defense mechanisms, such as release of
inflammatory cytokines, and in upregulation of costimulatory molecules,
thus providing cues that are essential to directing adaptive immune
responses. A single nucleotide polymorphism in the CD14 promoter that
is accompanied by increased levels of sCD14 has been found to be
associated with decreased total serum IgE levels. Functional genomics
studies have shown that the same polymorphism enhances CD14
transcriptional activity by decreasing the affinity of the promoter for
Sp proteins.
----------------
http://groups.google.com/groups/search?q=tlr-4+psoriasis&qt_s=Search
TLR-4
toll-like receptor 4 isoform B
TLR4 is a critical component of the heteromeric receptor complex that
transduces signals delivered by lipopolysaccharide (LPS) of
Gram-negative bacteria. CD14, a molecule selectively expressed by
monocytes and granulocytes, an d MD-2 are also involved in LPS-mediated
signaling. C3H/HeJ mice which bear mutations in the Tlr4 gene exhibit
defective LPS signaling, and TLR4 knockout mice are selectively
impaired in their ability to recognize Gram-negative bacteria. In
humans, TLR4 mutations have been found to be associated with endotoxin
hyporesponsiveness. Recognition of viral products has also been
proposed to be mediated by TLR4, and studies in animal models point to
a major role of TLR4 in the response to respiratory sync ytial virus
infection.
----------------------------------------------
LY96
lymphocyte antigen 96
Note that LY96 used to be called MD-2.
n mammals, LPS initiates its biological activities through a
heteromeric receptor complex containing CD14, TLR4, and at least one
other protein, MD-2. LPS binds directly to CD14 and is cross-linked
specifically to TLR4 and MD-2 only when co-expressed with CD14. Thus
LPS is in close proximity to the three known proteins of its membrane
receptor complex, and binds directly to each of the members of the
tripartite LPS receptor complex. MD-2 is a required component of the
LPS signaling complex and (similar to CD14) can function as a soluble
receptor for cells that do not otherwise express it. Molecular genetic
analysis of an LPS-nonresponder mutant cell line has recently shown
that a point mutation in a conserved region of MD-2 abolishes
LPS-induced signaling. Of note, decreased expression of MD-2 and TLR4
correlates with protection of intestinal epithelial cells against
dysregulated expression of proinflammatory genes in response to
bacterial LPS.
For more,
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605243
------------------------------
CTNNB1
catenin (cadherin-associated protein), beta 1, 88kDa
ß-catenin a transcriptional coactivator, is part of the intracellular
signal transduction pathways triggered by LPS in human macrophages, and
appears to be involved in both LPS-induction of gene transcription and
LPS-dependent regulation of vascular permeability. Exposure of alveolar
macrophages to bacterial LPS results in the activation of a number of
signal transduction pathways. An early event after the alveolar
macrophage comes in contact with LPS is activation of PI 3-kinase and
phosphorylation of Akt. In turn, Akt activation results in the
phosphorylation-dependent inactivation of glycogen synthase kinase
(GSK-3). Inactivation of GSK-3 reduces the ubiquitination of
ß-catenin, resulting in nuclear accumulation and expression of genes
that require nuclear ß-catenin for their activation. On the other
hand, LPS induces actin reorganization, increased paracellular
permeability, and endothelial cell detachment from the underlying
extracellular matrix. Components of cell-cell (γ- and ß-catenin) and
cell-matrix adherens junctions are cleaved by caspases activated during
apoptosis. Cleavage of focal adhesion kinase leads to its dissociation
from the focal adhesion-associated signaling protein, paxillin,
resulting in reduced paxillin tyrosine phosphorylation. Therefore,
endotoxin-induced disruption of endothelial monolayer integrity and
survival signaling events is mediated, in part, through caspase
cleavage of adherens junction proteins.
=======================================================
randall... Immunity and buffalo da'iry! A trend forming or what?
randall
P news from around the world.
We have a milk and macrophage theme going the last few
days.
Let's milk it again today!
randall wrote:
> Hi,
>
> Yesterday it was goat milk. Today try bison milk from the UK,
> http://www.timesonline.co.uk/article/0,,8126-2298194,00.html
<sniP>
And now it's how long you breastfeed for, as a factor in immunity?
That last bastion of all that's holy, including aPPle pie.
Got Mothers MILK?
http://www.newscientist.com/article/mg19125634.400?DCMP=NLC-nletter&nsref=mg19125634.400
MOTHER'S milk is undeniably the most nutritious food for babies, but
can they have too much of a good thing? While exclusive breastfeeding
during the first six months of a child's life is thought to help
prevent allergies, it is not clear whether further breastfeeding is
beneficial in this way.
Twenty years ago researchers at the Helsinki Skin and Allergy Hospital
in Finland asked 200 mothers of newborns to maintain exclusive
breastfeeding for as long as possible.
The children were assessed for allergies at ages 5, 11 and 20.
Exclusive breastfeeding for nine months or more actually appeared to
increase the chances of a baby developing allergic conditions such as
eczema and food hypersensitivity. At age 5, 56 per cent of children
with a family history of allergy who had been breastfed for nine months
or more had allergic symptoms, compared with 20 per cent of those who
had been breastfed for between two and six months.
The researchers noticed that children who developed allergies after
prolonged exclusive breastfeeding were most likely to do so during the
first years of life, suggesting that environmental factors such as
pollen exposure, diet and disease are the more important factors in the
onset of allergies in later childhood and early adulthood.
"A beautiful hypothesis is that there is a time window when the immune
system needs to be exposed to external antigens for it to develop
properly," says team member Maria Pesonen, although more research is
needed to be sure
------------------------------------------------------
How critical are Macrophages in P immunity?
Yesterday it was reported:
> Today we have three new abstracts, a troika of BIG MAC (macrophage)
> attacks and their influence on P.
>
<sniP>
Medical News today, picked uP this BIG MAC story today.
ARE the MAC's smacking our Plaques?
http://www.medicalnewstoday.com/medicalnews.php?newsid=48626
Psoriasis commonly appears as red, scaly, thickening patches of skin
called plaques and is believed to be either an immune-mediated disorder
in which T cells become active, migrate to the skin, and trigger an
immune reaction causing inflammation and a rapid turnover of skin
cells, or simply a fault in the skin cells themselves. Two separate
studies appearing in the August issue of the Journal of Clinical
Investigation, in different mouse models of psoriasis, now report that
macrophages play a key role in inducing psoriasis-like skin disease.
Karin Scharffetter-Kochanek and colleagues from the University of Ulm
studied a mouse model of psoriasis in which inflammation is T
cell-dependent, whereas Ingo Haase and colleagues from the University
of Cologne studied a T cell-independent mouse model of psoriasis.
Strikingly, both groups report an important contribution by
macrophages, implying that macrophages can contribute to both
epithelial-based and T cell-mediated pathways of inflammation in this
chronic skin disorder.
In an accompanying commentary, Rachael Clark and Thomas S. Kupper from
Brigham and Women's Hospital, Boston, comment that the results of these
two studies suggest that macrophages in the dermis, once activated by T
cells or cytokines expressed by dendritic cells, produce large amounts
of TNF-alpha, leading to psoriasis lesion formation. These authors go
on to conclude that, "The underlying events that lead to macrophage
recruitment and activation remain to be fully characterized and may
result from either autoreactive T cells or aberrant epidermal signals.
Further clarification ...will lead to treatments that can strike at the
true source of this chronic inflammatory skin disease."
<sniP>
Mac back paddy whack. Give the psoriatic a bone.
Toss it somewhere else. We want to know for sure.
So? Is it a T cell bet?
http://www2.hawaii.edu/~johnb/micro/micro161/T_and_B_activation_chap10/T_and_B_activation_chap10.htm
That was basic.
----------------------------------------
More basic?
Take it from a horse. Your not gonna finish first with inflammation
hanging around,
http://www.thehorse.com/viewarticle.aspx?ID=4328
Good basic immunity for those in the know!
Or do you pick your horse based on color? lol
I like the red scaly horse mom, keep breastfeeding me! <g>
-------------------------
Try not to get hot under the collar. Inflammation can kill.
http://www.slate.com/id/2147154/
---------------------
Being skewed towards a Th1 ( T helper one cells) is a bad bet if you
have P genes.
http://www.medscape.com/viewarticle/436533_10
[...]
Regulatory cells: Th cells and Ts cells . Th cells produce multiple
lymphokines that promote the proliferation and activation of other
lymphocytes and macrophages. There are 2 types of Th cells: Th1 cells
and Th2 cells. Th1 cells produce cytokines (IL-2 and IFN-gamma) that
activate macrophages to kill antigen-containing cells. Th2 cells
produce enzymes that activate B cells to produce antibody. The
cytokines produced by Th2 cells give chemical instructions to immune
cells to: enter a site of antigen concentration, proliferate in
response to antigen (IL-4 and IL-5 induce proliferation of B cells),
and directly kill or phagocytose antigen (cytotoxic cytokines affecting
T cells include lymphotoxin and TNF-beta, IFN-gamma activates
macrophages). Thus, cytokine-producing Th cells effect antigen
clearance by producing the molecules that activate immunocompetent
cells in the presence of antigen (Figure 15). Cytotoxic T cells effect
antigen clearance by directly killing cells whose surface tissue
antigens become altered by exposure to infectious organisms or damaging
toxins. Like phagocytes, CTLs depend on Th cell-produced cytokines to
do their job.
[...]
In addition to being functionally distinct, T cell subset populations
have different surface antigens or "markers" called clusters of
differentiation (CD) that can be detected by mAbs. CD4 and CD8
molecules are found on the surfaces of Th and Tc cells, respectively.
CD4+ T cells recognize antigen combined with HLA class II molecules;
CD8+ T cells recognize antigen combined with HLA class I molecules.
[...]
Lymphokines are 1 of the 2 soluble products of lymphocytes, the other
being antibodies. Lymphokines and monokines (released from monocytes)
are inflammatory and regulatory hormones of the immune system that
serve a variety of functions, such as the recruitment of macrophages to
antigen sites (chemotaxis), augmentation of T cell function in general,
and inhibition of viral replication. Lymphokines carry molecular
signals between immunocompetent cells for amplification of the immune
response. Their role in amplification of the T-cell response is crucial
to cellular immunity. There are many lymphokines, including families of
related cytokines, which are listed in Table 5.
Table 5
http://www.medscape.com/content/2002/00/43/65/436533/436533_tab.html#Table%205.
And there is our TNF and IFN
I'm still betting on LPS (endotoxin) as the main factor for the Th1
skew.
After that we need a mix of P genes that have been reported in the
psoriasis newsgroup.
Are the P genes at work in the plaques and can they be turned off with
a toPical?
Seems to be the message du jour.
Yet, we still have to deal with the TH1 skew systemically.
Don't we?
randall... we want action in our massage!
randall
P News from around the World.
First stoP. LOURDES France
This is keeping in theme with the religious posts last week.:)
lourdes the last resort,
http://www.theaustralian.news.com.au/story/0,20867,20009588-5002031,00.html
The Lourdes site,
http://www.lourdes-france.com/index.php?page=menu&texte=1&old=&langage=en
Hey! WEbcam,
http://www.lourdes-france.org/index.php?id=507&contexte=en
Just checked the Groto cam. All you can see are a bunch of folks
streaming
thru. They look like the shadows in the back of Plato's cave. lol
--------------------------------------------------
Portland Oregon in the news with the NPF.
http://biz.yahoo.com/prnews/060807/cgm017.html?.v=56
Press Release Source: National Psoriasis Foundation
Newly Launched Psoriatic Arthritis Resource Puts Patients on PATH to
Better Physical and Emotional Health
Monday August 7, 7:22 am ET
Novel program developed as new survey finds patients experience
misunderstanding, embarrassment due to disease symptoms
PORTLAND, Ore., Aug. 7 /PRNewswire/ -- For people living with psoriatic
arthritis, a disease characterized by pain, stiffness and swelling in
and around the joints, physical symptoms may not be the only source of
pain. According to a new survey released this week from the National
Psoriasis Foundation, people with psoriatic arthritis suffer
psychological effects due to the impact of psoriatic arthritis on their
appearance and the social stigma associated with physical symptoms of
the disease. Psoriatic arthritis was also found to impact everyday
life. To address the needs of people with psoriatic arthritis, the
National Psoriasis Foundation is introducing the Psoriatic Arthritis
Total approach to Health (PATH), a program providing tools and
information for managing the physical and emotional aspects of the
disease.
[...]
The centerpiece of PATH is an online resource on the National Psoriasis
Foundation Web site ( http://www.psoriasis.org/PATH ) featuring tips
from experts on reducing stress, exercising, eating well and
incorporating other healthy living tactics into everyday life, to help
relieve the impact of psoriatic arthritis. The site also includes tips
on skincare and style. <sniP>
--------------------------------------------------------------
Spiritual Healing from Aspen Colorado. Coming to a town
near you?
http://www.aspentimes.com/article/20060727/NEWS/107270058
randall... but, do they have a web cam showing cave-ish silhouettes?
randall
I was going to run this tomorrow. But what the heck.
Does God care what you shove down your pie hole?
Does it say somewhere in scriptures about taking care of yourself?
Don't fork yourself! Eating many foods that are inflammatory will
create
psoriasis.
If you don't believe me. Do your own tests.
What's in the press?
Lets see.
ONE fat meal and the INFLAMMATORY imPlications.
http://www.cbsnews.com/stories/2006/08/07/ap/health/mainD8JBRI480.shtml
One High-Saturated Fat Meal Can Be Bad
CLEVELAND -- Eating just one meal high in saturated fat _ in this case,
carrot cake and a milkshake _ can quickly prevent "good" cholesterol
from protecting the body against clogged arteries, a small study shows.
The results of the research weren't a surprise to the experts, but they
say the findings reaffirm something that more people need to
understand:
"What we put into our mouth makes a big difference in terms of our
health," said Dr. Charles McCauley, a cardiologist with Marshfield
Clinic in Wisconsin, who reviewed the research but wasn't involved with
the study. "We really have to be very careful as to how our food is
processed and what kind of ingredients we use."
In the study, at The Heart Research Institute in Sydney, Australia, 14
people, ages 18-40, ate two meals of carrot cake and a milkshake one
month apart. One meal was high in saturated fat _ using coconut oil _
and the other was high in polyunsaturated fat _ using safflower oil.
Saturated fat has long been linked to the buildup of plaque that can
lead to heart attacks and strokes. HDL, the "good" cholesterol,
protects arteries from the inflammation that leads to artery-clogging
plaques. And plaque hurts the ability of arteries to expand to carry
blood to tissues and organs.
The researchers, led by Dr. Stephen Nicholls, a cardiologist now at the
Cleveland Clinic, found that three hours after eating the saturated-fat
cake and shake, the lining of the arteries was hindered from expanding
to increase blood flow. And after six hours, the anti-inflammatory
qualities of the good cholesterol were reduced.
But the polyunsaturated meal seemed to improve those anti-inflammatory
qualities. Also, fewer inflammatory agents were found in the arteries
than before the meal.
"They're looking at things in terms of real live living," said
McCauley. "Carrot cake. How more real does that get?"
The study appears in the Aug. 15 issue of the Journal of the American
College of Cardiology.
"It's a simple study. Sometimes the best studies are those that are
very straightforward," said Dr. Richard Milani, head of preventive
cardiology at Ochsner Clinic Foundation in New Orleans.
He notes that the research isn't suggesting that people eat a steady
diet of carrot cake and milkshakes.
However, he said, "given a choice between something with
polyunsaturated fat and saturated fat, please avoid the saturated fat."
Nicholls said "the take-home, public-health message is this: It's
further evidence to support the need to aggressively reduce the amount
of saturated fat consumed in the diet."
Saturated fats are found mostly in food from animals, including beef,
pork, lard, poultry fat, butter, milk and cheeses, and some plants,
including coconut oil, palm oil and cocoa butter.
Polyunsaturated fats are found in oils from plants, including
safflower, sesame and sunflower seeds, corn and soybeans, many nuts and
seeds.
Dr. James O'Keefe, a cardiologist at the Mid America Heart Institute in
Kansas City, said Nicholls' study shows "a really important concept _
when you eat the wrong types of food, inflammation and damage to the
vessels happens immediately afterward."
Too many people simply are eating the wrong kind of fats, O'Keefe said.
"Even one meal of a double cheeseburger with fries and a Coke will mess
up your system, let alone a steady diet of it, which is recipe for
disaster," O'Keefe said.
--------------------------------
This is a no-brainer. All fat and fatty cells (adipose) are loaded with
TNF. TNF creates flakes.
Biologicals block TNF.
StoP TNF = StoPPing Psoriasis!
______
On the Net:
American Heart Association: http://www.americanheart.org/
Journal of the American College of Cardiology:
http://www.cardiosource.com/jacc/index.asp
The Heart Research Institute: http://www.hri.org.au/
================================================
Well, this is a NO brainer.
If you cheat eat. You must comPensate for it.
How?
Fat meals with omega-6's that lead to arachidonic acid can be blocked
about 25% by taking plant sterols and stanols.
http://www.nipponseika.co.jp/eng/fragrance/sterol.htm
Four or five 900mg caplets and you've blocked at least a quarter
of that bad fat. Not a lot, but enough to make a difference if you eat
half
as much. While slurPppping down that fat, toss down some crudites.
Slices of carrots, tomatoes, celery and other veggies will fill you up
while the fat satifies the cravings.
You can cheat eat. Just not as much and with blocking bad fats the P
flares droP to minimum levels.
This is what I take,
http://ec1.images-amazon.com/images/P/B00094K13I.01-A3E0B40Y2AC8FQ._SCLZZZZZZZ_.jpg
& where I get it,
http://www.costco.com/Browse/Product.aspx?ec=BC-EC4528-ProdID11093557&pos=1&whse=&topnav=national&prodid=10043333
And to really understand it check out all 26 slides,
http://www.lipidsonline.org/slides/slide01.cfm?q=plant+sterols&dpg=1
___________________________________________________
--------------------------------------------------------------------
P NEWs.... now.. from around the world
Some alternatives from Africa, around cape town.
The quantera machine,
http://www.naturalmedicine.co.za/sajnm_main/article.php?story=20040126085504989
Dr Bernard Brom
MB ChB (UCT), CEDH (France), Dip Acup
The Quanterra is a medical device with EU registration, now also
registered for use in South Africa. It was developed in Russia as part
of the space programme and soon spread throughout that country as a
home device for treating common ailments.
<sniP>
Meditation,
http://www.naturalmedicine.co.za/sajnm_main/article.php?story=20031103112102795
>From TJ mexico to Cape town Aftica with a fruit and veggie diet.
http://www.naturalmedicine.co.za/sajnm_main/article.php?story=20031208103043662
Nola Davidson
Colon therapist, clinical nutritionist, RN, RM, Psych/Comm Health Dip
I have recently returned from Tijuana, Mexico, after completing a
therapist/practitioner training course at the Baji Nutri Clinic. At
this clinic patients are treated according to Gerson's therapy.
<sniP>
http://www.naturalmedicine.co.za/sajnm_main/article.php?story=20040109105734399
The African potato, also known as Hypoxis rooperi, has been around for
centuries. It has been used by traditional healers, mainly in
KwaZulu-Natal and the Eastern Cape. A problem in the past has been
quality control. Roots have been sold in markets and by the wayside,
and roughly ground dried roots have been contaminated or have lost
their potency. More recently, Hypoxis rooperi has been grown
commercially, with controlled harvesting and preparation.
With international research showing the benefits of plant ingredients,
known as phytonutrients, the spotlight has been turned onto South
African indigenous plants. Professor Patrick Bouic from the University
of Stellenbosch has shown the beneficial effect of plant sterols and
sterolins on the immune system. Research done on a group of volunteers
demonstrated a significant increase in the number of T-cells, which are
involved in enhancing immunity.1
In addition, there is evidence that plant sterols, mainly
beta-sitosterols, in the African potato, have a beneficial effect on
benign prostatic hypertrophy or enlargement of the prostate gland.2
However, the long-term use of sterols and sterolins derived from the
African potato is not advisable due to its immuno-suppressive effect.
People's Plants, a well-illustrated and informative book by Dr Nigel
Gericke and Professor Ben van Wyk, provides background knowledge on
many South African plants, including the African potato. In the past,
traditional healers regarded it as a 'wonder plant' and used it for a
variety of ailments, and as a convalescent and strengthening tonic.3
Apart from research showing beneficial effects on prostatic
hypertrophy, and stimulation of the immune system, there are various
medicinal claims made for the plant. Hypoxis rooperi is said to have
anti-inflammatory effects and would therefore be useful in patients
with rheumatoid arthritis. Anecdotal reports claim benefits in chronic
fatigue, eczema and psoriasis, recuperation after chemotherapy and
debilitating illnesses.
---------------------------------------------------
randall... go for it. You never know what power God has given you!
randall
P News from around the world.
Aryurvedic psoriatic treatments in the Hindustan Times,
http://www.hindustantimes.com/news/5922_1763606,0015002500010000.htm
It's a new lease of life for her SMRITI Malaviya
Allahabad, August 8
THIS RAKHI, 25-year-old Anita (name changed) can hope to celebrate the
festival like any of her normal cousins. Till three years back it was a
dreaded dream for Anita, the only child of her parents, after having
been diagnosed with psoriasis- a lifelong skin disease in which red
patches appear on the skin. Let aside tying a Rakhi, her cousins even
avoided to accept anything from her, as the lesions covered with a
silvery white build-up of dead skin cell, called scale started to
spread on her hands.
But thanks to Ayurveda, after one year of treatment Anita can again
think of leading a normal life and even get married.
Resident of Chail, Anita was diagnosed with suffering from plaque
psoriasis, a most prevalent form of disease. She had developed
inflamed, red lesions covered by a silvery white scale on her elbows,
knees, scalp and lower back. Her skin started scaling and she found
difficult to move out in sunlight. When moving out she had to cover
both her hands with cloth to avoid displeasing glares of people.
As the news of her disease spread, relatives stopped calling her to
social events. She became a total recluse within two years who waited
for her end to come.
What worse, the doctors told her that it was a hereditary problem
(since her mother also suffered from psoriasis in a minor form) and she
would have to live with the disease all through her life.
The medicines given to her created unpleasant side effects and Anita
had no choice but to drop the medicines, which further aggravated her
condition.
"When she was brought to the Aryurveda clinic, the psoriasis had spread
to other parts of body. She was instantly started with Panchkarma
(cleaning blood or pittaj vyadhi) followed by three to seven days of
Virechan Kriya (cleaning of stomach). Sunita was also given Shirodhara
of butter milk (matha) and Bakuchi oil and Somraji oil (in 3:1) for
applying on the affected areas. She was given some Ayurveda medicines
and allopathic antioxidants to relieve her condition.
Within three months of treatment the scaling on her skin gradually
stopped and the normal skin lustre returned on her skin," said
Ayurvedacharya Dr SK Rai.
Dr Rai said the most important thing was that Anita had regained her
confidence and now wants to further pursue her studies.
"Three more psoriasis patients are being treated, who have shown
positive results," he added.
-------------------------------------------------
Ehtiopian weed works on psoriasis.
http://allafrica.com/stories/200608080002.html
Ethiopia: 'Weed' Has a Green Future
[...]
UK biotechnology entrepreneur, Tony Atkinson, was working on "an
exciting range of pharmaceutical applications for vernonia oil". The
oil speeds up wound healing and alleviates psoriasis. The oil seals
broken skin, in a process similar to the action of epoxy glue.
<sniP>
Let's see this herb outa africa,
http://www.ars.usda.gov/Main/docs.htm?docid=8143
&
http://ss.jircas.affrc.go.jp/project/africa_dojo/Fakara_plants/Contents/Species%20pages/Vernogal.html
========================================================================
New Abstracts from Pubmed.
Advances in cathepsin S inhibitor design.
* Link JO,
* Zipfel S.
Gilead Sciences Inc, 344 Lakeside Drive, Foster City, CA 94404, USA.
john.link @gilead.com
Cathepsin S is expressed in antigen-presenting cells and plays a role
in invariant chain processing and major histocompatibility complex
class II (MHCII) antigen presentation leading to CD4+ T-cell
activation. An oral cathepsin S inhibitor that blocks MHCII antigen
presentation could result in a T-cell-selective immunosuppressant agent
with improved safety over the current standard of care for the
treatment of rheumatoid arthritis, psoriasis, multiple sclerosis and
other autoimmune-based inflammatory diseases. This review focuses on
advances in cathepsin S inhibitor utility and design since January of
2004.
PMID: 16889230
Invariant chain looked promising for T cell workings,
http://groups.google.com/groups/search?q=invariant+chain+psoriasis&qt_s=Search
Here's a mouse model of MS,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16878136&query_hl=8&itool=pubmed_docsum
Invariant V(alpha)19i T cells regulate autoimmune inflammation.
* Croxford JL,
* Miyake S,
* Huang YY,
* Shimamura M,
* Yamamura T.
Department of Immunology, National Institute of Neuroscience, National
Centre of Neurology and Psychiatry, Tokyo 187-8502, Japan.
T cells expressing an invariant V(alpha)19-J(alpha)33 T cell receptor
alpha-chain (V(alpha)19i TCR) are restricted by the nonpolymorphic
major histocompatibility complex class Ib molecule MR1. Whether
V(alpha)19i T cells are involved in autoimmunity is not understood.
Here we demonstrate that T cells expressing the V(alpha)19i TCR
transgene inhibited the induction and progression of experimental
autoimmune encephalomyelitis (EAE), a mouse model of multiple
sclerosis. Similarly, EAE was exacerbated in MR1-deficient mice, which
lack V(alpha)19i T cells. EAE suppression was accompanied by reduced
production of inflammatory mediators and increased secretion of
interleukin 10. Interleukin 10 production occurred at least in part
through interactions between B cells and V(alpha)19i T cells mediated
by the ICOS costimulatory molecule. These results suggest an
immunoregulatory function for V(alpha)19i T cells.
PMID: 16878136
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16870416&query_hl=8&itool=pubmed_docsum
CD1d- and MR1-restricted invariant T cells: of mice and men.
* Treiner E,
* Lantz O.
Laboratoire d'Immunologie, Inserm E0351, Faculte de Medecine, 3 Rue de
Louvels, 80036 Amiens Cedex, France.
CD1d-restricted natural killer T cells and MR1-restricted mucosal
associated invariant T (MAIT) cells constitute two subsets of
unconventional T cells that are phylogenetically conserved. Therefore,
they are thought to play an essential role within the immune system.
MR1-restricted MAIT cell selection is dependent upon B cells, and their
accumulation in the gut lamina propria and mesenteric lymph node
requires the commensal bacterial flora. These features suggest that
MAIT cells could be involved in tolerance or immunity to infections in
the gut. As for natural killer T cells, the recent identification of
one endogenous ligand, isoglobotrihexosylceramide, and of a family of
bacterial agonists is an important advance for understanding their
thymic selection and their role during infections.
PMID: 16870416
A gut, thymus and skin connection with immunity?
randall... we can only hoPe and Pray!
randall
P New from the NPF conference. Time to find a cure!
http://biz.yahoo.com/prnews/060808/sftu127.html?.v=38
Press Release Source: National Psoriasis Foundation
National Psoriasis Foundation Kicks Off Finding a Cure Campaign at 2006
National Conference
Tuesday August 8, 7:22 pm ET
PORTLAND, Ore., Aug. 8 /PRNewswire/ -- Nearly 300 conference attendees
at the National Psoriasis Foundation® 2006 National Conference
gathered Aug. 4-6 to share common experiences and learn about new
treatment options for their psoriasis and psoriatic arthritis. But they
walked away with much more-a sense of hope that a cure will be found
for these diseases
Fueling that hope was the kickoff of Finding a Cure: The Campaign for
the National Psoriasis Foundation, which aims to raise $5 million for
research and advocacy in an effort to a find a cure for psoriasis.
Prior to the conference, $3.3 million had been raised through the
campaign. An additional $8,000 was contributed at the conference.
One of the highlights of the conference was the announcement of a $1
million pledge to the campaign by the Henschel family of Boca Raton,
Fla., through the Barbara and Neal Henschel Charitable Foundation. The
contribution was made in honor of the late Victor Henschel, who had
severe psoriasis and psoriatic arthritis. The gift is dedicated solely
to the creation of the National Psoriasis Victor Henschel BioBank, a
major component of the research initiative of the Finding a Cure
campaign. The BioBank will hold the world's largest collection of
psoriasis and psoriatic arthritis biological samples for use by
researchers.
The campaign's advocacy initiative includes both government relations
(the Foundation's political efforts on Capitol Hill in Washington,
D.C.) and work with patients, doctors and insurance companies to
achieve better access to treatment.
"Ramping up our efforts in research and advocacy is an important step
in finding a cure for psoriasis and psoriatic arthritis," says Gail M.
Zimmerman, president and CEO of the National Psoriasis Foundation. "The
Finding a Cure campaign will help raise funds to support us in this
work."
Workshops focusing on advocacy and research were a major part of this
year's conference, demonstrating the importance of these initiatives in
finding a cure for psoriasis. Keynote speakers included Stephen Katz,
M.D., Ph.D., director of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases at the National Institutes of Health,
and Alan Menter, M.D., chairman of the Division of Dermatology at
Baylor University Medical Center in Dallas, Texas, and a key leader in
the field of psoriasis.
For more information on psoriasis, or to make a donation to Finding a
Cure, visit the National Psoriasis Foundation Web site,
www.psoriasis.org, or call 800-723-9166.
About Psoriasis
Psoriasis is a chronic, noncontagious genetic disease of the immune
system that prompts skin cells to regenerate too quickly, causing red,
scaly lesions that crack and bleed. It often affects the elbows, knees,
scalp and torso but can appear anywhere on the body. Ten percent to 30
percent of people with psoriasis also develop psoriatic arthritis, an
inflammatory disease which causes pain, stiffness and swelling in and
around the joints. According to the National Institutes of Health, as
many as 7.5 million Americans have psoriasis. Psoriasis can affect
anyone at any age, including children. There is no cure yet for
psoriasis.
About the National Psoriasis Foundation
The National Psoriasis Foundation is the leading patient-driven,
nonprofit organization dedicated to improving the quality of life
millions of Americans with psoriasis and/or psoriatic arthritis, and
their families. We focus on education, advocacy and research toward
better treatments and a cure. For more information, please call the
Psoriasis Foundation, headquartered in Portland, Ore., at 800.723.9166,
or visit www.psoriasis.org
=========================================================
Don't use use your biologicals uPon rising. SleeP info.
http://abclocal.go.com/kgo/story?section=edell&id=4399742
Research Summary: Sleep Inertia
BACKGROUND: Researchers have been aware of what's known as "sleep
inertia" for several decades. It's defined as a decline in motor
dexterity and a subjective feeling of grogginess, immediately following
an abrupt awakening
A University of Colorado study is the first to assess this
physiological state and how we perform tasks while in it. The
researchers monitored people who slept eight hours per night for a
month. The study participants were given a performance test that
involved adding randomly generated, two-digit numbers.
THE RESULTS: The study revealed subjects exhibited the most severe
impairments from sleep inertia during the groggy period upon awakening.
Test subjects had diminished short-term memory, counting skills and
cognitive abilities. The most severe effects of sleep inertia generally
dissipated within the first 10 minutes, although researchers say its
effects are often detectable for up to two hours
IMPLICATIONS: Anyone who performs critical tasks immediately after
waking may be vulnerable, since researchers found the cognitive
deficiencies that occur when some people first wake up are comparable
to the effects of alcohol intoxication.
There are possible implications for medical professionals who care for
patients in crisis on a moment's notice, 'round the clock. In addition,
medical residents can work 80 hours or more per week, and could be
prone to make simple math mistakes when calculating dosages of medicine
during bouts of sleep inertia. Emergency medical technicians may also
be at risk. They may be hastily awakened and called to drive to an
emergency scene, putting themselves and others at risk. The study also
cites possible complications for commercial truck drivers, who
frequently pause for quick naps in their vehicles during cross-country
trips.
PREVENTION: Axon Sleep Research Laboratories in Providence, R.I., is
beginning the testing phase of a new type of alarm clock called Sleep
Smart. The idea is based on minimizing morning grogginess by waking
sleep-deprived people during the optimal time in their sleep cycle. The
"clock" is designed to monitor brainwaves to pinpoint the best time for
that individual to wake up. Clinical trials at Rhode Island Hospital in
Providence are scheduled for later this summer, but some experts want
to see more data before validating the science on which Sleep Smart is
based.
If the tests prove successful, the entrepreneurs -- three Brown
University students -- plan to work with a design firm to get the
product ready for store shelves next year.
-------------------------------------------------
randall...
randall
P News from around the world.
http://releases.usnewswire.com/GetRelease.asp?id=70471
Psoriasis Cure Now Releases New Podcast about 'Biologics Breakthrough'
in Psoriasis Treatment
8/9/2006 7:32:00 AM
To: National Desk, Health Reporter
Contact: Michael Paranzino of Psoriasis Cure Now, 202-253-4863 or
michael @psorcurenow.org ; Web: http://www.psorcurenow.org
KENSINGTON, Md., Aug. 9 /U.S. Newswire/ -- "Psoriasis Cure Now," a
nonprofit patient advocacy group, today released the newest in its
series of psoriasis podcasts, this one focused on the biologic
treatments that are revolutionizing psoriasis disease management. The
heart of the podcast is an interview with Ivor Caro, M.D., medical
director of Dermatology at Genentech and a former Harvard Medical
School faculty member who conducted clinical trials on many of the
biologics now coming to market for psoriasis and psoriatic arthritis.
The free podcast is available on the Psoriasis Cure Now website at
http://www.psorcurenow.org/podcasts.php , or through iTunes.
"Many people with moderate to severe psoriasis have heard some buzz
about biologics as a psoriasis treatment, but do not have a clear
understanding of the benefits and risks of these novel treatments,"
said Michael Paranzino, president of Psoriasis Cure Now. "This podcast
is designed to serve as an introduction to these treatments for
psoriasis patients and their loved ones. Given how many lives are being
transformed by these treatments, we hope it encourages patients to
discuss with their physicians whether these treatments might make sense
for them."
Biologics target elements of the immune system that lead to the
overproduction of skin cells and inflammatory activity that
characterize psoriasis and psoriatic arthritis. The goal is to improve
disease symptoms without the potentially serious side effects sometimes
seen in older psoriasis treatments including PUVA, cyclosporine and
methotrexate. Five different biologics, including Genentech's Raptiva,
are currently being used to treat people with psoriasis, or in some
cases, psoriatic arthritis. They are given either by injection or by
intravenous infusion. The podcast touches on the safety profile of
biologics, their efficacy and their mechanisms of action, and considers
what we still do not know about these relatively new treatments.
In addition to the interview with Dr. Caro, the podcast also includes
reviews of two recent book that include depictions of psoriasis, as
well as an excerpt from a song by Philadelphia- based singer-songwriter
Nik Everett, who happens to have psoriasis in addition to a smooth
voice and strong sense of melody. The next psoriasis podcast will be
released around Labor Day.
http://www.usnewswire.com/
-------------------------------------------------
For those of you without podcasting ability. Italy, the winner of the
2006
world cuP (soccer), has a site with a few biological tiPs.
http://www.xagena.it/news/medicinenews_net_news/e2521b89f813157a3f50c5c8d0d3086b.html
NICE, options for the treatment of psoriasis and psoriatic arthritis in
adults
The NICE ( National Institute for Health and Clinical Excellence ) has
developed guidance on the use within the NHS in England and Wales of
Etanercept ( Enbrel ) and Efalizumab ( Raptiva ) for the treatment of
psoriasis, and Etanercept and Infliximab ( Remicade ) for the treatment
of psoriatic arthritis.
[...]
The guidance on the use of Etanercept and Efalizumab for the treatment
of psoriasis recommends:
- The use of Etanercept, within its licensed indications, as an option
for the treatment of adults with severe plaque psoriasis when: other
treatments haven't worked ( for example, Ciclosporin, Methotrexate
and ultraviolet radiation ) or, the person is intolerant to, or has a
contraindication to, these treatments.
- Treatment with Etanercept should be discontinued if the person's
psoriasis has not shown a measured response after 12 weeks. Further
treatment cycles are not recommended in these patients.
- Efalizumab should be offered as an option for treating adults with
severe plaque psoriasis if: treatment with Etanercept has not worked or
the person is intolerant of, or has contraindications to, treatment
with Etanercept.
- Treatment with Efalizumab should be discontinued if the person's
psoriasis has not shown a measured response after 12 weeks.
An measured response is defined as either:
- a 75% reduction in the PASI score from when treatment started ( PASI
75 ) or
- a 50% reduction in the PASI score ( PASI 50 ) and a five-point
reduction in DLQI 2 from when treatment started.
The guidance on the use of Etanercept and Infliximab for the treatment
of psoriatic arthritis recommends:
- Etanercept should be offered as an option for the treatment of adults
with severe active psoriatic arthritis when: the person has peripheral
arthritis with three or more tender joints and three or more swollen
joints and other DMARDs, administered either individually or in
combination, have not worked.
- Treatment with Etanercept should be discontinued if the person's
psoriatic arthritis has not shown a measured response after 12 weeks.
- Infliximab should be offered as an option for treatment for treating
adults with severe active psoriatic arthritis if: treatment with
Etanercept has not worked or, the person is intolerant of, or has
contraindications to, treatment with Etanercept.
- Treatment with Infliximab should be discontinued if the person's
psoriatic arthritis has not shown a measured response after 12 weeks.
A measured response is defined as an improvement in at least two of the
four Psoriatic Arthritis Response Criteria ( PsARC ), one of which has
to be joint tenderness or swelling score, with no worsening in any of
the four criteria.
Source: NICE, 2006
-----------------------------------------------------------
In Canada, dermylex reporting good news for mild to moderate
psoriatics.
http://www.npicenter.com/anm/templates/newsATemp.aspx?articleid=16279&zoneid=28
Advitech Announces Positive Results For a Third Application Of The
XP-828L Platform and Publication Of a Second Scientific Paper On
Dermylex
2006-08-09 - Advitech, Inc
[...]
Dermylex™ is Advitech's orally administered product for mild to
moderate plaque psoriasis made from a bioactive ingredient with proven
clinical efficacy. On July 5, 2005, the Company reported positive
results from its Phase II clinical trial for treating mild to moderate
psoriasis. The 112-day, multi-center, double blind, placebo-controlled
study, involving 84 patients, confirmed the efficacy and excellent
safety profile of Dermylex™ for treating mild to moderate psoriasis.
For more information please visit www.dermylex.ca
-------------------------------------------------------------
Can sleeP help? Go to bed and get some and find out!
Deep sleep is vital to our wellbeing
Aug 9 2006
WHEN we sleep, hormones are released, breathing and heart rates, blood
pressure and body temperature drop, and our memory is consolidated.
Studies suggest a lack of routine, too little or too much sleep can
harm mental and physical health.
Q. Why is a good night's sleep important?
A. Our inbuilt body clock responds to sunlight and our 24-hour social
pattern, controlling production by the liver of key enzymes to deal
with the meals we eat and toxic by-products.
A Cambridge study shows daily rhythm changes caused by shift work, jet
lag, certain sleep disorders and old age, can affect our metabolism
including how blood, fats and sugars are regulated, and may even
increase the risk of developing certain cancers.
Q. What happens without enough sleep?
A. Lack of sleep is associated with a twofold increase in obesity
levels in adults and children as young as five, and is thought to be
caused.
Time for bed: The right amount of sleep could help prevent heart
problems and diabetes.
by hormonal changes. It can also make the onset of diabetes more
likely.
Even healthy individuals experienced increased blood pressure with less
than five hours' sleep a night.
Sleep quality is also important. Some people suffer from sleep apnoea -
when they stop breathing for at least 10 seconds during sleep,
partially awakening them but not enough to remember next morning.
It is more common in the overweight or obese, and sufferers often tend
to snore.
They are likely to have an increased risk of coronary heart
disease,hypertension, congestive heart failure, heart rhythm disorders,
enhanced furring of the arteries and increased levels of C-reactive
protein, a risk factor for heart disease.
Q. Is getting too much sleep also bad?
A. Research has shown sleeping more than nine hours nightly, and
working shifts may double the risk of Parkinson's disease and triple
the risk of diabetes, a risk factor for heart disease.
Getting the right amount of sleep is important for general health and
mental alertness but can also help ward off high blood pressure and
reduce the risk of heart, stroke and kidney disease.
Rest times are also essential to enable the heart to pump more easily.
Q. How much sleep should I have?
A. Whether you powernap, have a lunchtime siesta, a quick 40 winks
after work or prefer uninterrupted nights, the key is to establish a
routine favouring deep sleep.
You'll know how well you've slept by how fresh and rested you feel when
you wake.
Tips for getting the good night's sleep we need include avoiding late
night TV, large meals and high carbohydrate snacks, caffeine and
alcohol before bed, and exercising regularly.
The general consensus is around six to eight hours' sleep nightly is
best.
* For more information and advice about healthy living, call Heart
Research on 0113 297 6206 or e-mail life...@heartresearch.org.uk
-----------------------------------------------------------
randall....
randall
P News from around the world.
This link was posted back on January 10, 2006 in P NEWS.
http://www.docguide.com/news/content.nsf/news/8525697700573E18852570F20051D6D3
[...]
LEO Pharma submitted the NDA for Taclonex to the FDA in March 2005.
Taclonex is a topical ointment containing a combination of
calcipotriene 0.005% and betamethasone dipropionate 0.064% for the
treatment of psoriasis vulgaris in adults. Taclonex is sold outside the
U.S. as Dovobet(R) or Daivobet(R).
Warner Chilcott acquired the U.S. marketing rights for Dovonex(R)
(calcipotriene (calcipotriene 0.005%), the leading non-steroidal
topical treatment for psoriasis in the U.S., from Bristol-Myers Squibb
Company as of January 1. Warner Chilcott is now LEO Pharma's exclusive
licensee of Taclonex and Dovonex in the United States. Warner Chilcott
expects to launch Taclonex in the first half of 2006.
"Taclonex presents an exciting proposition for the treatment of
psoriasis in the U.S., and we are preparing for its launch with great
anticipation," said Roger Boissonneault, CEO of Warner Chilcott.
<sniP>
Roger was right. Taclonex is working for those using it. At least one
person
I know personally has had exlnt results. And is a severe psoriatic.
Anyone else out there with a story to tell?
-------------------------------
NOW, look at this study. An oinment for P that works BETTER then the
biologicals!
http://www.drugnewswire.com/4632/
Ointment More Effective Than Recently NICE-Approved Biologics, Given as
Injections in Treating Severe Psoriasis, New Study Suggests
August 10, 2006 - 11:30 AM
LONDON, August 10/PRNewswire/ -- A routinely prescribed ointment
applied once a day, which is a combination of two existing treatments
for psoriasis - calciptriol and betamethasone dipropionate - is more
effective in the severe form of the condition than some recently
NICE-approved biological treatments, according to a new study published
this month in the leading skin journal the International Journal of
Dermatology.
This new analysis looks at results of carefully controlled clinical
trials for different psoriasis treatments in the severe form of the
condition - the combination ointment, and three of the biological
therapies, relatively recently introduced monoclonal antibody
therapies, which are administered by injection and cost between GBP2030
and GBP4290 per treatment course[1].
In this new assessment, a retrospective analysis of six studies
involving 2,452 patients treated with the calcipotriol and
betamethasone dipropionate combination ointment, demonstrated that in
the 261 patients with severe psoriasis, 88.8% improved by 50% or more
after four weeks of treatment. Analysis of a further five,
double-blind, placebo controlled trials of biological treatments
involving 1703 patients, demonstrated that 56%, 59% and 74% improved by
50% or more after 12 weeks in patients treated with alefacept,
efalizumab and etanercept respectively. Everyone who entered the
biologic trials had severe psoriasis at treatment commencement[2].
<sniP>
---------------------------------------------
Taclonex (aka- dovobet, daivobet) is working better then the
biologicals!
I wonder if it's cheaper then learning how to effectively use sweet
whey?
I did a cost comparison a year or so ago now of just that. But taclonex
wasn't in that comparison.
Of course since then i've added in more suPPlements that have
allowed me to eat a variety of foods high in arachidonic acid and still
maintain sub 4% levels (Pasi). What's not to like. :)
------------------------------------------------------
If this next dude had P, like some say. He simply blows my mind.
Maybe his p levels were late onset and he had cruiser's constitution?
Always on the go. I'm so jealous as my get uP and go, got uP and went.
:(
-----------------------------------
http://www.americanscientist.org/template/BookReviewTypeDetail/assetid/53125;jsessionid=baa8kAxfcQiRf3
Reflected Light?
Barry W. Allen
Doctor Franklin's Medicine. Stanley Finger. xiv + 379 pp. University of
Pennsylvania Press, 2006. $39.95.
Few personalities swept a more luminous arc through 18th-century
America than did Benjamin Franklin. An autodidact, polymath, patriot
and successful businessman, he was wealthy enough at the age of 42 to
retire from commerce and devote the rest of life to philanthropy,
diplomacy and science. Among many achievements, he may have been the
first to have the powerful insight that the various manifestations of
electricity are a single phenomenon best understood as a kind of fluid.
Franklin's celebrity was due to his formidable intelligence,
unparalleled energy and admirable assiduity, and also to circumstance:
He owned a printing press, and his literary alter ego, Poor Richard,
had something to say about almost everything of interest to a broad,
Colonial audience.
Franklin also actively sought fame, and some of his renown was
self-created: He dissimulated humility while inwardly belittling it. "I
cannot boast of much Success in acquiring the Reality of this Virtue,
but I had a good deal with regard to the Appearance of it," he wrote
candidly in his Autobiography. He smoothly ingratiated himself with
many of the best thinkers and doers of his time, without seeming to
try, but trying all the while, especially in his younger years. To gain
the attention or favor of someone important, he suggested, one should
ask to borrow a book from that person's library-a marvelously
disingenuous method of flattering even the most wary. He also counseled
that older mistresses are to be preferred because they are so much more
grateful.
The remainder of the book is organized chronologically and by
scientific discipline. Finger describes Franklin's contributions to the
emerging recognition of the health benefits of exercise and fresh air,
the promotion of inoculation against smallpox, the establishment in
America of the first hospital and then the first medical school, the
formation of scientific and medical societies, the understanding of
airborne contagion and lead poisoning, the resolution of the struggle
between theorists and pragmatists in medicine, and advocacy for the
therapeutic role of music. The last chapters deal with Franklin's more
intimate connection to medical conditions from which he personally
suffered: presbyopia, gout, a chronic skin disease (presumably
_____psoriasis__) and bladder stones.
<sniP>
------------------------------------------------------
If you figure this next one out, let me know.
http://washingtontimes.com/metro/20060809-110536-9744r.htm
Oppose psoriasis? Ward 3 has a candidate for you
TOM KNOTT (METRO)
By Tom Knott
August 10, 2006
Theresa Conroy is a member of an endangered species in local politics
-- a Republican who is seeking to represent Ward 3 on the D.C. Council.
Her challenge is daunting, if only because the city eschews the
two-party system and considers Republicans to be the bane of all ills,
including psoriasis.
At least Mrs. Conroy is being spared the sharp analysis of Thelma
Roque, the political pundit who devotes her attention to the nine
Democrats crowding the Ward 3 field.
Mrs. Conroy also has not been linked to the vast number of
conspiracies lurking on the Internet, many of which cite DCist.com as
the cause of all the problems in Ward 3, including psoriasis.
Mrs. Conroy claims not to feel like the loneliest person in the
city, if not the political version of "The Last of the Mohicans."
"You don't do this unless you think you can win," she said by
telephone yesterday. "I think the message of positive resolutions could
resonate with voters [in November]."
Until then, the fiercest struggle is taking place among the
Democratic candidates.
Eight of the nine Democratic candidates came out against psoriasis
in a debate that aired on NewsChannel 8 this week.
Each plans to fix the city's public-school system, lower property
taxes and extend the life span of each resident by 10 years.
Mary Cheh also plans to maintain her teaching position at George
Washington University because being a council member is merely a
part-time job.
Sam Brooks, who appears to have just graduated from high school, is
touting "25 ideas to move us forward," one of which is to urge council
members to eat healthier food during their "Tuesday breakfasts" on the
first Tuesday of each month.
As the city's shadow senator for the press 10 years, Paul Strauss
is coming out of what amounts to the Witness Protection Program. As low
as his profile is, he might as well be a congressional aide.
part II,
http://washingtontimes.com/metro/20060809-110536-9744r_page2.htm
-------------------------------------
POLITICS AND PSORIASIS. Glad we don't have that problem here.
randall... Can taclonex change one's politics? It ain't that good! LOL
randall
P News from around the world.
http://www.zeenews.com/znnew/articles.asp?rep=2&aid=315041&ssid=28&sid=ENV
[...]
Replying to supplementaries, the Minister cited a news item in a daily
claiming that two Jaipur-based dermatologists stating that permanent
cure had been achieved while treating patients of psoriasis with
antibiotic drugs such as penicillin and azithromycin.
Large-scale clinical trials would be required to validate their claim
using these routine antibiotics used in clinical practice, he told the
questioner.
-------------------------------------------------
Do we need better antibiotics? Could the first story be true? Didn't
Ben Blavat find this line of treatment to work for him?
Yes, if iirc.
Newer and better antibiotics then?
And how much will the YMMV factor weigh in then?
http://www.paramuspost.com/article.php/20060810233409961
The bottom of the ocean can be a dark, cold and muddy place, but this
forbidding environment could hold life-saving antibiotics derived from
organisms that scientists have never seen.
Now the University of California San Diego will soon undertake an
ambitious effort to fast-track the process of discovering new compounds
from the sea floor to turn them into antibiotics. University officials
will draw from talent at their Scripps Institution of Oceanography and
their schools of pharmacy and medicine. They also will enlist the
support of San Diego County's biotech community and venture
capitalists.
"The ocean has been a completely unexplored resource for drug
discovery," said Bill Fenical, a Scripps researcher and co-architect of
the initiative.
[...]
Seven years ago, Fenical began exploring the sea floor off Guam, Hawaii
and even at the end of the Scripps Pier in San Diego to find chemicals
for new medicines.
"These ocean bottoms are inhabited by a whole new set of microbes that
make compounds that are antibiotic, have anti-cancer properties and are
chemically novel," Fenical said. "When you think about how vast the
ocean is - you know, 70 percent of the surface of the Earth is covered
by oceans - the potential for this is enormous." Two chemicals that
Fenical's lab discovered are in early clinical trials to treat cancer,
he said.
Now, Fenical and a team of researchers from other UCSD departments want
to explore the sea for new antibiotics. They aim to minimize the
academic boundaries between oceanographers, chemists, pharmaceutical
scientists and physicians, Fenical said. The UCSD initiative is likely
unique, said David Newman, acting chief of the Natural Products Branch
of the National Cancer Institute in Bethesda, Md.
"I do not personally know of any other group, in what is basically a
one-square-mile area, with this concentration of abilities," Newman
said.
In its March report, the National Academy of Sciences warned about an
early 40-year-old "innovation gap" in pharmaceutical companies' pursuit
of new antibiotics.
A large reason for the lapse has been a decision by the pharmaceutical
industry to reduce or cease efforts to develop antibiotics. By the late
1980s, half of the largest drug companies in the United States and
Japan had announced that they were reducing research, Nizet said.
"There's just not enough money in it" for these firms, Fenical said.
In the government arena, the National Institutes of Health provides
about $28 billion annually for much of the basic biomedical research in
the country, but none of that money goes toward drug development. That
leaves the new UCSD initiative searching for funds. Fenical and Nizet
plan to solicit money from their area's biotechnology community,
including venture capitalists. Licensing agreements would be written so
that UCSD and the scientists who discover new antibiotics share a small
percentage of any future royalties. Fenical said he might seek support
from the Bill and Melinda Gates Foundation, which recently announced
that it would receive $31 billion from financier Warren Buffett. The
foundation, among its health and educational causes, aims to fight the
spread of AIDS and other infectious diseases in the developing world.
A strong case can be made that the search for new antibiotics is
critical for everyone, Fenical said.
"More and more, the diseases of the developing world are the same as
ours," he said.
_________________________________________________________
The pond scum bug or the bottom of the ocean bacteria, make no
difference
to me.
Make and prove it and we'll take it.
Cure us NOW. NO MORE singing the summertime P blues!
randall...
manfred
Susan wrote:
> x-no-archive: yes
>
> randall wrote:
> > Hi,
> >
> >
> > P News from around the world.
> >
> > http://www.zeenews.com/znnew/articles.asp?rep=2&aid=315041&ssid=28&sid=ENV
> >
> > [...]
> >
> > Replying to supplementaries, the Minister cited a news item in a daily
> > claiming that two Jaipur-based dermatologists stating that permanent
> > cure had been achieved while treating patients of psoriasis with
> > antibiotic drugs such as penicillin and azithromycin.
> >
> > Large-scale clinical trials would be required to validate their claim
> > using these routine antibiotics used in clinical practice, he told the
> > questioner.
>
>
>
> OTOH, my derm treated a patient with an infection with Diflucan and an
> antibiotic and cured a 15 y.o. case of P. Hasn't come back yet.
>
> What about antimicrobial topicals, such as Bactroban or Flagyl?
>
> Susan
Perhaps taking the antibiotics for an extended period is the key:
Eur J Dermatol. 2005 Sep-Oct;15(5):359-62. Links
Long-term use of penicillin for the treatment of chronic plaque
psoriasis.Saxena VN, Dogra J.
Unit of Dermatology, SMS Medical College, Jaipur India.
drvns...@rediffmail.com
A continuing sub-clinical streptococcal infection might be responsible
for chronic plaque psoriasis. In this open study, we investigated
thirty patients with moderate to severe chronic plaque psoriasis. The
majority of the patients had been ill for 5 years or more (21 out of
the total 30), and they had taken various treatment modalities for
psoriasis with no significant improvement and frequent relapses. Total
duration of the study was two years. Initially benzathine penicillin
1.2 million units, was given I.M. AST fortnightly. After 24 weeks
benzathine penicillin was reduced to 1.2 million units once a month.
Relevant investigations and clinical assessment was done at regular
intervals to detect side effects and to observe the progress of
disease. Significant improvement in the PASI score was noted from 12
weeks onwards. All patients showed excellent improvement at 2 years.
Patients tolerated the therapy well. Controlled studies are needed to
further confirm the benefits of long-term use of benzathine penicillin
in the treatment of psoriasis.
manfred
Susan wrote:
> x-no-archive: yes
>
> randall wrote:
> >
> >
> > P News from around the world.
> >
> > http://www.zeenews.com/znnew/articles.asp?rep=2&aid=315041&ssid=28&sid=ENV
> >
> > [...]
> >
> > Replying to supplementaries, the Minister cited a news item in a daily
> > claiming that two Jaipur-based dermatologists stating that permanent
> > cure had been achieved while treating patients of psoriasis with
> > antibiotic drugs such as penicillin and azithromycin.
> >
> > Large-scale clinical trials would be required to validate their claim
> > using these routine antibiotics used in clinical practice, he told the
> > questioner.
>
>
randall
> Susan wrote:
> > x-no-archive: yes
> >
> > randall wrote:
> > > Hi,
> > >
> > >
> > > P News from around the world.
> > >
> > > http://www.zeenews.com/znnew/articles.asp?rep=2&aid=315041&ssid=28&sid=ENV
> > >
> > > [...]
> > >
> > > Replying to supplementaries, the Minister cited a news item in a daily
> > > claiming that two Jaipur-based dermatologists stating that permanent
> > > cure had been achieved while treating patients of psoriasis with
> > > antibiotic drugs such as penicillin and azithromycin.
> > >
> > > Large-scale clinical trials would be required to validate their claim
> > > using these routine antibiotics used in clinical practice, he told the
> > > questioner.
> >
> >
> > I've taken high doses of those and doxycycline for years. No dice.
An obvious case of YMMV. Mine does too. Vary that is.
Ben Blavat otoh responds really well to this line of treatment.
See his posts,
http://groups.google.com/groups/search?q=ben+blavat&start=0&scoring=d&
Furthemore,
LOOK at J's post today on vaccination and shifting from Th1 to Th2.
Which means less TNF with Th2. Certainly that should help psoriatics
as well. Yet, many still have pathways that aren't clear yet (no pun
intended),
and would also fall under YMMV. :(
Hey! Good find Manfred. You found the derms in India who did the
above mentioned study..
So? What do we do with this?
Mikhail in Russia would treat Group B strep, eliminate LPS (endotoxin)
and clear P.
Is it all a case of subclinical strep then? I find it hard to believe.
So while
some folks like Ben Blavat may clear for a period of time, wouldn't
the nature of simply living and bumping in to people, as well as being
in tight embraces now and then <g>, invite more strep? And subsequent
psoriasis flares then? We all have strep toPically, how do we live
then?
In a bubble? The key would still be to fix the gut to produce Th2
cytokines
like IL-10 to keep the teeter toter of immunity in balance.
========================================
Time for P News.
In India today. Lupin still testing desoside-P (former desoris?),
http://www.equitybulls.com/admin/news2006/news_det.asp?id=503
Lupin receives DCGI approval to conduct Phase II clinical Trials for
Psoriasis NCE
Lupin Ltd announced that it has received approval from Drugs Controller
General (India) (DCGI) to conduct Phase - II Clinical Trials for its
Psoriasis pure compound LL-42 18 (Desoside-P).
The DCC has found Clinical Phase I data of LL-4218 (Desoside-P)
satisfactory and has granted the Company permission to continue Phase
II Clinical Trials on the molecule. The Company intends to begin
clinical trials at 5-6 centres immediately.
LL-4218 is a pure molecule and is obtained from a plant source. It is
orally bioavailable and is intended for the treatment of chronic stable
plaque type psoriasis. This molecule's novel mechanism of action
leads to marked psoriatic lesion improvement without any toxic effects.
<sniP>
------------------------------------------------------
I wonder what plant is used for Desoris and now Desoside-P?
These lupin guys are tight liPPed. I can't find a thing online.
There is an ayurvedic topical using Cassia tora going around.
Here's a psoriatics moms' testimony for her son,
http://www.topix.net/forum/health/psoriasis/TK5CDVS0UDJD10OB0
What is it?
http://www.psoriasis-tab.com/?gclid=CLjA-5-E3YYCFR-PWAoddhA05w
[...]
Psoriasis Tab is a completely guaranteed and clinically proven herbal
treatment for Psoriasis.
It consists of a formulation consisting of purely natural ingredients
of the herbal genus Cassia blended together in a specific proportion to
fight and cure Psoriasis permanently.
Thousands of patients have been successfully cured with Psoriasis Tab
over the past few years. Psoriasis Tab is a completely outstanding
product and there is absolutely no alternative to its unique formula.
Had the effectiveness of Psoriasis Tab not been proven beyond any
doubt, it would not be possible for us to make such a bold claim.
<sniP>
go to their pdf for more info.
========================================================
Doctors, Nurses and pilots alert. Go to mexico for cheap and heal
people.
http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2006/08/13/TRG1AKDRDT1.DTL
[...]
The patients' problems were pretty much the same ones the doctor
encountered at home: acne, psoriasis and eczema were common. But most
of their complaints had been untreated for years, if ever. Whenever
possible, the doctor was wonderfully inventive with simple, inexpensive
cures. I was surprised to learn, for example, that repeated
applications of duct tape can remove warts.
<sniP>
You have to ask the obvious question. How bad would a psoriatic look if
he moved north away from
the sunshine at this latitude? I know i clear quickly down there. :)
==============================================
Capsaicin for P?
http://www.thetidenews.com/article.aspx?qrDate=08/13/2006&qrTitle=Pepper%20your%20life%20a%20little%20longer&qrColumn=KALEIDOSCOPE
___________________________________________________
>From pubmed abstracts in the last few days.
eNOS gene in psoriasis pathways?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16891095&query_hl=6&itool=pubmed_docsum
Association of eNOS gene polymorphism (Glu298Asp) with psoriasis.
<>Senturk N
Department of Dermatology, Ondokuz Mayis University Medical Faculty,
5139 Kurupelit Samsun, Turkey.
PMID: 16891095
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15825252&query_hl=6&itool=pubmed_docsum
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16020391&query_hl=15&itool=pubmed_docsum
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16247331&query_hl=15&itool=pubmed_docsum
Chronic ethanol sensitizes the liver to endotoxin via effects on
endothelial nitric oxide synthase regulation.
* Karaa A,
* Kamoun WS,
* Clemens MG.
Department of Biology, University of North Carolina, Charlotte, North
Carolina 28223, USA.
In vivo studies have shown that chronic alcohol consumption sensitizes
the liver to endotoxemic shock, leading to liver microcirculation
disruption. In the present study, we investigated the molecular
mechanisms involved, focusing on endothelial nitric oxide synthase
(eNOS) activity and regulation, which represents one of the major
vasodilatory pathways. Male Sprague-Dawley rats were fed an alcohol
liquid diet or a control isocaloric diet for 5 weeks. Priming effects
of ethanol were studied in a model with or without a 24-h LPS treatment
(1 mg/kg body weight). At the end of the diet, liver tissue was
harvested for western blot, reverse transcriptase-PCR, histological
analysis, and immunostaining and blood for serum alanine
aminotransferase analysis. Chronic ethanol and LPS alone induced a mild
hepatitis and infiltration, respectively. Combined, LPS and chronic
ethanol feeding showed a synergistic effect on the liver, leading to
extensive steatohepatitis with extensive focal necrosis associated with
significantly higher levels of serum ALT. Chronic ethanol and LPS
significantly inhibited eNOS activity, but exerted their effects
through different mechanisms. Caveolin-1, an eNOS inhibitory protein,
was upregulated after LPS and chronic alcohol consumption.
Additionally, chronic alcohol consumption down-regulated endothelin B
receptor, eNOS protein levels, and eNOS phosphorylation. In conclusion,
chronic ethanol consumption and LPS share a similar pathophysiology and
both lead to the impairment of eNOS activity, but through distinct
molecular mechanisms. The presence of focal necrosis in a mild stress
model could provide a good animal study to investigate the advanced
stages of alcoholic liver diseases.
PMID: 16247331
http://cgmp.blauplanet.com/reg/enos.html
[...]
Besides myristoylation, eNOS protein suffers another changes such as
palmitoylayion, phosphorylation and specific interactions with another
proteins. After those modifications the eNOS protein is active and
synthetizes NO or in some cases superoxide ion (this later circunstance
can take place when the substrate, L-arginine, or tetrahydrobiopterin
are deficient and has pathophysiological consequences). Then, all these
non-permanent modifications of eNOS revert and eNOS is deactivated. A
cycle of activation-deactivation occurs in parallel with a cycle of
association and dissociation from the caveoale at the plasma membrane.
Intracellular localization
eNOS is predominantly localized in caveolae (specialized invaginations
of the plasma membrane), where it is closely regulated by interaction
with caveolin-1. Modifications preventing membrane localization of eNOS
also result in the absence of NO synthetic activity in the intact
cells. Membrane distribution is probably needed by the presence in the
same localization of other proteins important for eNOS activity: the
cationic amino acid transporter CAT-1 (involved in the uptake of
L-arginine, substrate for NO synthesis), calcium pump and the
bradykinin receptor are also present in caveolae.
Although membrane distribution is an essential requirement for eNOS
activity, at plasma membrane the enzyme activity is closely regulated
by caveolin-1. This intrinsic protein strongly reduces eNOS activity by
interfering with calmodulin binding. Intracellular calcium increase or
shear stress displace caveolin-1 and allow eNOS activation.
Membrane localization of eNOS is modulated by certain
post-translational modifications:
myristoylation and palmitoylation (Fig. 2). Myristoylation distinguish
eNOS from nNOS and iNOS, that are predominantly cytosolic proteins.
Although in vitro activity of myristoyl-deficient eNOS is not impaired,
eNOS is inactive and not localized in membrane in cells mutated in the
myristoylation site.
Palmitoylation is also required for a proper localization of eNOS in
the membrane. This latter modification, in contrast to myristoylation,
has a rapid turnover and it has been proposed to be promoted by
bradykinin stimulation and to be related with caveolin-1 displacement.
Phosphorylation
(Tyr-Phosphorylation, Ser/Thr-Phosphorylation)
Oxygen free radicals
In addition to direct regulation of NO-synthases, NO availability is
also dependent on the quantity of oxygen free radicals generated by
cells surrounding NO-producer cell. In fact, eNOS may generate
superoxide instead of NO in certain conditions (e.g. low L-arginine
levels). Whatever the origin of superoxide (eNOS, xanthine oxidase,...)
this compound rapidly reacts with NO to form peroxynitrite. In certain
pathological circunstances an increase in superoxide formation can be
determinant in reducing NO availability.
(and I ran out of time with this line of inquiry. :(
++++++++++++++++++++++++++++++++++++++++++++++++++++
randall...
----------------------------------------
randall
P News from around the world.
Let's look at immunity news first.
http://www.medicalnewstoday.com/medicalnews.php?newsid=48280
Flick Of A Protein Switches Immune Response
A single protein can turn on and off a key component of the immune
system by changing partners in an elegant genomic dance, said
researchers at the University of Southern California and Harvard
Medical School.
Because autoimmune diseases - such as arthritis, allergies and dozens
of other illnesses - begin when the body's defenses respond at the
wrong time or place, the on-off mechanism for the immune system has
been the subject of intense study for decades.
The USC-Harvard team studied proteins critical to immune tolerance, a
term for the healthy balance between a weak immune system and an overly
aggressive, indiscriminate watchdog.
Lin Chen, professor of molecular and computational biology at USC and
lead co-author with Harvard's Anjana Rao, said the team's result would
"open a big door for people to explain the fundamental mechanism of
immune tolerance."
In the July issue of Cell, the USC-Harvard group shows that the protein
Nuclear Factor of Activated T cells (NFAT), in collaboration with
FOXP3, an essential factor in regulatory T cells, orchestrates a
genetic program critical to immune tolerance.
But the same NFAT, paired with a second family of proteins known as
AP-1, instead stimulates immune response.
Chen said the finding offers the first strong evidence in favor of the
15-year-old "combinatorial control" theory of gene expression.
According to the theory, the specific expression of a gene depends on
the combination of "transcription factors" acting on it. Transcription
factors help to translate a gene's instructions into actual proteins.
FOXP3 and NFAT are two such factors; the human body contains around
3,000.
"The work provides a structural demonstration of combinatorial control
of gene expression," Chen said. "This is, in my view, the most direct
demonstration that this is indeed happening in nature."
The researchers were able to identify single genes that were activated
by NFAT in combination with AP-1 and suppressed by NFAT with FOXP3.
Beyond shedding light on the immune system, the Cell paper may advance
biology and medicine toward a much larger goal: how to turn single
genes on or off.
"This [result] has far-reaching implications for understanding the
principles of signal transduction and transcriptional networks of
living cells," Chen said.
The Cell paper, which Chen describes as spanning 14 years of laboratory
work, builds on a result his group published in Nature in 1998.
--------------------------------------------------------------------
Ap1 flicks the P plaques? Yeah! It flicks me off. Or is that on?
http://groups.google.com/groups/search?q=ap1+psoriasis+activator&qt_s=Search
-------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=49416
Interferon-gamma Keeps Over-aggressive Immune Responses In Check
Regulatory T cells (Tregs) are a specialized subpopulation of T cells
that act to suppress overactivation of the immune system and prevent it
from turning upon self-tissues.
Initially, the expression of two cell surface molecules (CD4 and CD25)
was used to define the Treg population of cells; as such they are often
referred to as CD4+CD25+ Tregs. More recently the transcription factor
Foxp3 has been identified to be exclusively expressed by Tregs and is
known to play a key role in the conversion of CD4+CD25- T cells to
CD4+CD25+ Tregs.
In a study in mice appearing online in August in advance of print
publication in the September issue of the Journal of Clinical
Investigation, Jingwu Zhang and colleagues from the Shanghai Institute
of Immunology have shown that interferon-gamma is required for the
induction of Foxp3, resulting in the conversion of CD4+CD25- T cells to
CD4+CD25+ Tregs. These results reflect the critical role that
interferon-gamma plays in maintaining a balanced immune response: in
the event of overt inflammation as a result of injury or infection,
interferon-gamma acts as part of a self-regulatory mechanism to help
keep the immune response in check by triggering the development of
Tregs. This mechanism likely plays a role in other pathological
conditions involving inflammation.
-------------------------------------
Abstract du jour from pubmed.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16904202&query_hl=2&itool=pubmed_docsum
Calcitonin gene-related peptide regulates the expression of vascular
endothelial growth factor in human HaCaT keratinocytes by activation of
ERK1/2 MAPK.
* Yu XJ,
* Li CY,
* Wang KY,
* Dai HY.
Department of Dermatology, Qilu Hospital, University of Shandong, Jinan
250-012, China.
Psoriasis is a chronic disease characterized by abnormal epidermal
proliferation, inflammation and angiogenesis. The pathogenetic process
resulting in hypervascularity remains to be further investigated. It
has been reported that a potent angiogenic factor, vascular endothelial
growth factor (VEGF) is overexpressed in psoriatic epidermis and that
the level of calcitonin gene-related peptide (CGRP) is elevated in
psoriasis lesions and CGRP-containing neuropeptide nerve fibers are
denser in the psoriatic epidermis. We hypothesized that CGRP might
regulate the expression of VEGF by human keratinocytes. VEGF expression
in the CGRP-treated human keratinocytes was investigated and the CGRP
signaling pathways were examined with respect to VEGF expression. The
mRNA and protein levels of VEGF by CGRP were increased in a
concentration-dependent manner. However, this increase was abrogated by
pretreatment with an extracellular signal-regulated kinase (ERK)
inhibitor PD98059. The CGRP-mediated VEGF induction was also
effectively inhibited by a pretreatment with the CGRP receptor
antagonist CGRP 8-37. In addition, CGRP treatment induced rapid
phosphorylation of ERK1/2, PD98059 and CGRP 8-37 were able to inhibit
CGRP-induced ERK1/2 phosphorylation. These results suggest that CGRP
regulates the expression of VEGF through the CGRP receptor and ERK1/2
MAPK signaling pathway in human HaCaT keratinocytes.
PMID: 16904202
Is P erk-ing you off?
http://groups.google.com/groups/search?q=ERK1%2F2+MAPK.+psoriasis&qt_s=Search
----------------------------------------------
Some of us are gonna want this antifungal. Cruiser take note!
http://www.medicalnewstoday.com/medicalnews.php?newsid=49248&nfid=nl
Anacor Pharmaceuticals, a privately held company, today said that a
15-patient, Phase 1 trial of its lead compound, AN2690, showed that
patients receiving the topical treatment had no measurable level of the
drug in their bloodstream. AN2690 is the first in a new class of
antifungal agents that is being developed for onychomycosis, a fungal
infection of the nail and nail bed.
The 15 patients in the absorption study, who were required to have at
least eight infected nails, received daily treatments for 28 days with
a 7.5 percent solution of AN2690. The drug could not be found at
quantifiable levels (lower limit of quantification of 25 nanograms/ml)
in the blood at any time point on days 1, 14 and 28, when blood samples
were taken. Levels of AN2690 in the nail plate remained at therapeutic
levels 14 days after the end of treatment. Samples will continue to be
collected to evaluate the drug concentrations in the nail at longer
durations post-dosing.
"These new findings confirm preclinical toxicology work and showed that
while the drug will concentrate at its target, the nail bed, it is not
present at quantifiable levels in the bloodstream," said Dr. Karl
Beutner, Anacor's chief medical officer. "The level of drug found in
the nail plate during AN2690 treatment was substantially higher than
those found with currently available topical and oral agents."
In addition, cultures of all nails were taken at the end of the 28 days
of treatment, and all cultures were negative for the fungus, an early
indication of potential clinical efficacy.
Anacor also has completed enrollment in its 180-patient, double-blind,
placebo-controlled study. This study is being conducted by
investigators in both the United States and Mexico. An additional
open-label study evaluating drug concentrations as low as 1 percent
also has been fully enrolled. This trial consists of 60 patients and is
being conducted in the U.S. Three-month results for both of these
studies will be available in the fourth quarter of this year.
Anacor also announced the recent publication of the initial discovery
and characterization work of AN2690 in the Journal of Medicinal
Chemistry (volume 49, number 15). The article details the
structure-activity relationship investigation to find a more
efficacious treatment of onychomycosis that led to the boron-containing
small molecule AN2690.
AN2690 Phase 2 Program
Anacor is evaluating AN2690 in three Phase 2 studies. Primary endpoints
for all studies are greater than 5 mm clear nail growth at six months,
or nails judged by investigators to be "clear" or "almost clear," and a
negative culture for infection at the end of the trial period. The
first is an open- label study of 60 patients with onychomycosis who are
receiving either a 5 percent or 7.5 percent solution of AN2690 applied
once a day for six months. Recently reported preliminary interim
results from the first 90 days of this study in 24 patients receiving
the 5 percent solution showed 2.6 mm average "clear" nail growth, and
that 100 percent of fungal cultures were negative for infection after
30 days. The second study is a double-blind, placebo- controlled,
six-month trial of 180 patients who are receiving 2.5 percent, 5
percent or 7.5 percent solutions of AN2690 or a placebo. The third
trial is an open label study of 60 patients with onychomycosis who are
receiving either 1 percent of AN2690 daily for six months or 5 percent
AN2690 daily for one month followed by three times weekly treatment for
an additional five months.
<sniP
_________________________________________
I guess you could eat red meat? LOL
Is atkins the way? Or sweet whey the way?
Carb vs protein!
http://www.carbwire.com/2006/08/10/new_gene_found_in_fruit_flies_study_explains_why_atkins_diet_improves_metabolic_syndrome
A new study published in the August 8, 2006 issue of the scientific
journal Cell Metabolism provides further evidence of the health
benefits of the Atkins diet.
Burnham Institute for Medical Research assistant professor Dr. Sean
Oldham found a single gene called TOR in Drosophila fruit flies helps
to regulate vital body regulators such as insulin, glucose and fat
metabolism.
When Dr. Oldham and his research team mutated the TOR gene to see how
it impacted the fruit flies, what they found was a lowering of blood
glucose levels and cholesterol levels as well as a longer lifespan.
What does all of this mean for people who are livin' la vida
low-carb? Well, actually, this is NOT new information for us because we
already knew the Atkins/low-carb approach was an excellent way to
control insulin levels and blood sugar. Dr. Jeff Volek and Dr. Richard
Feinman have already previously "connected the dots" between low-carb
and metabolic syndrome and shared their discovery last year. It's nice
to know other researchers are finally catching up to this well-known
fact!
Despite this amazing discovery about how metabolic syndrome can be
treated naturally through a healthy low-carb diet, you are never going
to guess what the researchers are proposing to do in response to their
study. Click here (**) to read what they have planned and more on this
study that is yet another piece of scientific vindication for the late
great Dr. Robert C. Atkins.
(**)
http://livinlavidalocarb.blogspot.com/2006/08/study-gene-explains-why-atkins-diet.html
-------------------------------------------
H'mmm, this brings back evetsm's syndrome X.,
http://www.medicalnewstoday.com/medicalnews.php?newsid=49419&nfid=nl
Insulin controls in part how we metabolize both carbohydrates (glucose)
and fats through distinct signaling pathways, however researchers have
yet to identify if there is a shared element in these signaling
pathways. In a study in mice appearing online on August 10 in advance
of print publication in the September issue of the Journal of Clinical
Investigation, Domenico Accili and colleagues from Columbia University
show that a dual role exists for the transcription factor FoxO1 as the
shared element in insulin signaling that controls both fat and glucose
metabolism. They show that FoxO1 can have seemingly opposite effects on
metabolism, with the ultimate goal of fine-tuning insulin sensitivity.
FoxO1 increases insulin sensitivity by promoting Akt phosphorylation,
and this step is associated with the repression of the enzyme Trb3, a
modulator of Akt activity. This unexpected dual role of Foxo1 in
promoting insulin sensitivity and fat synthesis in addition to glucose
production has the potential to explain the mix of insulin resistance
and sensitivity that is commonly observed in individuals with the
metabolic syndrome. The study also suggests that Trb3 is an exciting
new target of insulin action and therefore understanding how Trb3 is
regulated has many ramifications for insulin resistance and diabetes.
<sniP>
--------------------------------------------
How does one eat right?
Why don't we eat the toP 10 foods instead?
How many are you eating?
http://www.medicalnewstoday.com/medicalnews.php?newsid=49475&nfid=nl
------------------------------------------------
And how do we fix the gut if it's leaking endotoxins?
Hasn't LPS been indicted for the Th1 skew?
Yes. So what?
Well. If we take some insurance out on the Gi tract, it's one less
thing to worry about.
Good point.
http://www.medicalnewstoday.com/medicalnews.php?newsid=49484&nfid=nl
Genotoxic Bacteria In The Digestive Tract
Escherichia coli is a commensal bacterium, which lives peacefully in
our digestive tract. However, certain strains are pathogenic and are
frequently incriminated in a broad spectrum of infections, affecting
both farmed animals and humans (diarrhoea, urinary tract infections,
food poisoning, septicaemia, neonatal meningitis, etc.). In this
respect, E. coli is a model bacterium to study the continuum between
commensal and pathogenic bacteria. Researchers at INRA in Toulouse, in
collaboration with German universities in Würzburg and Göttingen and
the Institut Pasteur in Paris, have shown for the first time that both
commensal and pathogenic E. coli produce a substance which is toxic to
the DNA in eukaryotic cells. The bacteria producing this toxin thus
induce DNA breaks in host cells and disturb the cell cycle. This
slowdown of eukaryotic cell proliferation may enhance bacterial
colonization of the intestine. On the other hand, if these breaks are
not repaired, they could give rise to a high level of mutations, which
are the principal factors triggering cancer in man. The details of this
work have been published in Science, August 11th 2006.
Colibactin, a new toxin which affects the host cell cycle
Certain strains of E. coli produce a toxin, which induces a toxic
effect in host cells, characterised by gradual cell enlargement
following the arrest of cell proliferation. INRA researchers in
Toulouse, in collaboration with teams at the German universities of
Würzburg and Göttingen and the Institut Pasteur in Paris, have
demonstrated that these bacterial strains possess a "genomic island" in
their genome, which contains all genes allowing the biosynthesis of a
new toxin, which they have called "Colibactin". The researchers have
shown that the bacteria producing this toxin induce serious lesions to
the DNA of host cells, causing a blockade of the cell cycle of infected
cells. Colibactin belongs to a new family of bacterial toxins, which
are able to act on the cell cycle of eukaryotic cells. The INRA
researchers have proposed to call this family the "cyclomodulins".
Colibactin is a non-protein toxin. The genes carried by the genomic
island code for several enzymes belonging to the family of "polyketide
synthetases" (PKS) and "nonribosomal polypeptide synthetases" (NRPS).
Compounds arising from these biosynthetic pathways constitute a large
family of natural products with a very broad range of biological
activities and pharmacological properties. This family comprises
numerous molecules which are of importance both agronomically
(anti-parasite substances, such as avermectin) and medically (e.g.
immunosuppressants, cholesterol-lowering agents, anticancer compounds
and antibiotics (cyclosporine, lovastatin, bleomycin, erythromycin,
etc.). This is the first time that an enzyme system of this type,
producing a molecule active on eukaryote cells, has been characterised
in E. coli, a bacterial species where genetic engineering is well
mastered. This discovery provides a biotechnological key to producing
new compounds of interest, and has been the subject of a patent
application. It opens the way to novel therapeutic approaches as well
as preventive opportunities.
Infectious diseases, cancer and anti-proliferative effects: is there a
role for bacteria producing cyclomodulins?
The work reported in Science also raises an important question for
public health. DNA double strand breaks are dangerous lesions affecting
eukaryotic cells; if these are not repaired, they give rise to a high
level of mutations, which are the principal triggers of cancer in man.
Colibactin is produced by both commensal E. coli in the intestinal
flora and pathogenic strains which are responsible for septicaemia,
urinary tract infections and meningitis. The presence of these bacteria
in the commensal flora may therefore constitute a predisposing factor
for the development of certain cancers. Thus bacterial flora may
participate in the development, differentiation and homeostasis of
mucosa and hence the development of certain types of cancer, or
protection against them.
About the INRA - PARIS
The National Institute for Agricultural research (Inra) was founded in
1946 and became a national public scientific and technological
establishment under the joint authority of the Ministries of Research
and Agriculture. Its objectives are: - to serve the public interest,
whilst maintaining consistency between its research goals and the
demands of society; - to acquire and disseminate information on
scientific knowledge and innovation, particularly in the fields of
agriculture, food and the environment; and - to contribute to
decision-making and training, to promote the transfer of scientific
knowledge and participate in the science-society debate.
INRA - PARIS
147, rue de l'Université
Service de presse
75338 Paris Cedex 07
--------------------------------------
Impaired gut? Drink this transgenic goat milk.
http://www.medicalnewstoday.com/medicalnews.php?newsid=48984&nfid=nl
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What if it tastes weird? Sour milk you say. Hey! get the umami tsunami!
http://www.medicalnewstoday.com/medicalnews.php?newsid=49100&nfid=nl
A team led by Duke University Medical Center researchers has discovered
two proteins in the taste buds on the surface of the tongue that are
responsible for detecting sour tastes.
While the scientific basis of other primary types of flavors, such as
bitter and sweet, is known, this is the first study to define how
humans perceive sour taste, said team senior scientist Hiroaki
Matsunami, Ph.D., an assistant professor of molecular genetics and
microbiology.
The identification of these proteins, called PKD1L3 and PKD2L1, could
lead to ways to manipulate the perception of taste in order to fool the
mouth that something sour, such as some children's medicines or health
foods, tastes sweet, he said.
The team's findings appear in the online edition of the Proceedings of
the National Academy of Sciences and will be published in the August
15, 2006, issue of the journal. The work was supported by the National
Institutes of Health.
Mammals, including humans, can detect five primary flavors: bitter,
sweet, salty, sour, and umami (known to the West as the taste of
monosodium glutamate or MSG). Each taste bud on the tongue contains
separate, distinct subsets of cells that specifically detect each taste
-- sweet cells respond to sweet substances, bitter cells to bitter
substances, and so on. Taste receptors, proteins on the surface of
these cells, are responsible for detecting the "taste" of a particular
food or chemical and triggering signals sent to the taste centers of
the brain.
In their study, the researchers used fluorescent tags to label the
subsets of cells that are known to be responsible for bitter, sweet,
and umami taste, as well as the subsets of cells that express PKD1L3
and PKD2L1. By "reading" the tags, they found no overlap between the
subsets of cells involved in the first three tastes and the cells in
which PKD1L3 and PKD2L1 are active. Matsunami said this result
suggested that those proteins could be responsible for sensing either
sour or salty taste.
In action, the two proteins combine to form "ion channels," porelike
proteins in the membranes of taste cells, Matsunami said. These
channels in turn control the flow of calcium ions, or electrically
charged forms of calcium, in and out of the cells. This flow of ions
essentially conditions the cell so that electrical signals can be sent
to the brain in response to various stimuli.
The researchers stimulated mammalian cells expressing PDK1L3 and PKD2L1
with various taste chemicals to identify which stimuli caused the ion
channels to open. To visualize the presence of calcium ions in the
cell, the scientists loaded the cells with two calcium-sensitive
fluorescent dyes -- one that glowed green when the calcium
concentration was high, the other that glowed red when the
concentration was low.
When they added sour-tasting acids to the cells, the ion channels went
from closed to open, enabling calcium ions to flow in, increasing their
concentration within the cell and changing the cells from red to green,
Matsunami said. The channels remained closed when confronted with salt,
sweeteners, or bitter solutions. The increased concentration of calcium
in the cell may then trigger the signal that the brain eventually
perceives as sour taste, he said.
Matsunami said he plans to use this finding to screen for chemicals
that can block the function of these sour taste cells. The research
also could lead to a better understanding of how the sense of taste
functions neurologically, he said. "We still do not know what is
happening in the brain -- that is, exactly how the brain would
interpret the signals coming from the tongue to tell the difference
between lemons and lemonade," Matsunami said. Future experiments using
live animals as test models will be needed to answer remaining
questions about taste sensation, he said.
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Zits and mice?
http://www.medicalnewstoday.com/medicalnews.php?newsid=49406&nfid=nl
Mice may not get zits, but they do have oily skin. This week, new
research on mice from Rockefeller University shows how the cells
responsible for oil production develop, and uncovers clues about how
stem cells renew and differentiate.
The research focuses on the skin's sebaceous gland, which is linked to
the hair shaft and secretes an oily mixture called sebum. But until
today how the sebaceous gland is formed during development was a matter
of debate: one group of scientists proposed that skin stem cells
produce the gland and a second group suggested that it had its own
progenitor cells. In new research, published in the August issue of
Cell, Elaine Fuchs, a Howard Hughes Medical Institute investigator at
Rockefeller University, settles this argument, showing that at the site
where the sebaceous gland adjoins the hair follicle, a unique
population of cells exists whose sole job is to make, and maintain, the
sebaceous gland.
"We were exploring the expression of a transcription factor called
Blimp1, which had surfaced in a genetic screen that we had conducted."
explains Fuchs, who is the Rebecca C. Lancefield Professor and head of
the Laboratory of Mammalian Cell Biology and Development at
Rockefeller. "We were surprised to find that Blimp1 was expressed in a
small population of cells within the sebaceous gland. We knew these
cells were skin keratinocytes but no one had ever described their
existence and therefore, we had no clues about their relationship to
the gland."
Valerie Horsley, a postdoc in the Fuchs lab and first author of the
paper, had been interested in Blimp1's role in hair follicle
development, and had engineered mice that were missing the Blimp1 gene
in their skin. "When the mice were born, they formed normal hair
follicles, which was quite disappointing," says Horsley. "But when they
were around one month of age I noticed that the mice started getting
very oily skin."
The sebaceous glands in mice missing Blimp1 were much larger than in
normal skin. This happens in another genetically altered mouse, one
overexpessing the c-myc gene, which has been implicated in many
different kinds of cancers. Horsley found that Blimp1 usually acts to
repress c-myc expression, and in mice without Blimp1 c-myc expression
was increased, causing the sebaceous gland to contain cells that divide
more frequently. When Horsley tagged the Blimp1 positive cells and
tracked them, she found that the daughters of the Blimp1 cells
contribute to the entire gland. Also, when grown outside in culture,
the cells that make Blimp1 can divide and self-renew, as well as make
the cell types important for generating the oils of the sebaceous
gland.
"The data show clearly that these cells are the progenitors for the
entire sebaceous gland," says Horsley. "And Blimp1 is somehow
controlling this progenitor population, regulating how many cells are
allowed into the gland. This is the first molecular characterization of
these cells."
"This study has implications for understanding sebaceous gland
disorders ranging from acne to sebaceous cell cancers," says Fuchs.
"And it not only gives us a handle on these novel resident stem cells,
but also clues to how stem cells can control the balance of
proliferation and differentiation in tissues."
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randall... happy 100th post in this thread! time to start over? yeP!