sPecial P News
randall
Did you see this site in ____P News____ today?
http://www.med-owl.com/psoriasis/tiki-index.php
One level up,
http://www.med-owl.com/
I received it in the mail last night and haven't stoPPed looking
at the pages.
This Med-Owl is right uP our alley! Loads of things to tinker with in
the diet.
And environs as well.... Limiting carbon based photocoPier and cig
smoke
may lower your skin exPerience of P.
We should get these guys a grant to run tests on P and smoke.
Psoriatics didn't hang in the caves when the fires were too smoky i'm
betting.
Anyone clear with an air ionizer?
====================================================
And here's another big plus for today. KeeP your HAIR on for this hit.
Found on google news only minutes ago!
http://www.ereleases.com/pr/20060531015.html
Press Release
Have Scientists Accidentally Discovered the Answer to Hair Loss?
SIMI VALLEY, Calif., May 31, 2006 -- Research scientists at the
University of San Francisco Wound Center may have stumbled onto the
answer to something that has frustrated mankind for centuries. Their
discovery was made while applying a synthetically formulated compound,
Copper Peptide, to severe wound areas on several patients. During this
process something unusual happened. Not only did the wounds heal about
30 percent faster, but a significant stimulation of the follicular
cells occurred. As a side effect, these tripeptide complexes actually
grew hair around the wound area.
The discovery was so startling that they then applied the same Copper
Peptide complex to a female patient who had suffered roughly 90 percent
alopecia (hair loss) for years. After about six months of use, she had
recovered almost 100 percent of her hair. Dr. Loren Pickart, the
leading authority in Copper Peptide technology, describes it as being
like a protein injection to the scalp.
Tests were then conducted with chemotherapy patients and recent hair
transplant recipients, all with great success in stimulating newer and
stronger hair follicles. The implications of such a startling discovery
have gotten the attention of several large companies. Neutrogena,
Johnson & Johnson, Procter & Gamble, and Dow Chemical are just a few of
the big companies that Dr. Pickart has turned down as potential
partners.
The discovery could have major implications in the somewhat shady area
of the hair growth industry. There are many products that promise
amazing results but they usually fail to deliver. Most have some sort
of DHT inhibitor with traces of Minoxidil so they can claim Food and
Drug Administration (FDA) approval. The only licensed company that has
been authorized by Dr. Pickart to manufacture for the public is Everest
R & D Labs, located in California's Simi Valley.
Incredible advancements in the manufacturing process of Copper Peptide
technology are bringing even better results in hair re-growth than the
original tests. Some people providing the company with feedback are
offering amazing stories, with positive side effects that include the
_____reduction____ of acne and _____psoriasis____. There have been many
reports from both men and women. Reports from women include statements
that their graying hair is regaining some of its original pigmentation.
This product has been integrated into a therapeutic shampoo and
conditioner called Follipro (http://follipro.com). As more and more
corroborating evidence from research universities around the country
become available, the possibilities for this new technology could be
far-reaching.
Contact:
Jacqueline Bodnar
JB @SyndicatedNews.us
(702) 338-3105
Source: Syndicated News, Inc.
+++++++++++++++++++++++++++++++++++++++++++++++++++
randall...Good Grief - More hair, less P! What's NOT to like?
randall
randall wrote:
> Special P News...
>
>
> Did you see this site in ____P News____ today?
> http://www.med-owl.com/psoriasis/tiki-index.php
> One level up,
> http://www.med-owl.com/
>
> I received it in the mail last night and haven't stoPPed looking
> at the pages.
>
> This Med-Owl is right uP our alley! Loads of things to tinker with in
> the diet.
>
Has anyone related to any of these pages by med-owl?
Like cutting out all the fructose in your diet!
>
>
>
> ====================================================
>
> And here's another big plus for today. KeeP your HAIR on for this hit.
>
> Found on google news only minutes ago!
>
> http://www.ereleases.com/pr/20060531015.html
Yet, live by the post and don't boast! lol
I did a quick check for photomedex and procyte. YeP somebody already
posted it as well,
http://groups.google.com/groups/search?q=procyte+photomedex+copper&qt_s=Search
The link for the patent on this puPPy didn't work. So maybe this one
will,
Read the patent please it's interesting. <w>
I sent an email to the inventor to get comments. Haven't heard back
yet.
randall... this coPPer thing brings back uP Loma Lux!!!???
123matt
tidbits of good info. Hey, is the Wholewhey kit still available? Do you
have the phone number/email address? I tried to call last summer but no
one ever returned my call. Are you getting your supply?
Hope all is well. Thanks for sharing info :)
Matt
randall
123matt wrote:
> Hi Randall! I just read about the photocopiers--and managed to pick up some
> tidbits of good info.
Matt,
Long time no hear. I'm taking it your P is a project still in the
works?
> Hey, is the Wholewhey kit still available?
Yes. They were out of business for a month or so, but back up now.
I've been in contact with a psoriatic that did the implant (wit kit)
recently and he's very happy with the results so far.
> Do you
> have the phone number/email address?
http://thewholewhey.com/Contact.htm
> I tried to call last summer but no
> one ever returned my call. Are you getting your supply?
I'm still using old supply that I found sitting on the self at my
local co-oP.
The proflora whey product, which was made by Land O"lakes
was halted for whatever reasons. So, we have the Jay Robb, sweet
dairy whey, now. I'm hoping that i can convince a local store to carry
it. Or i'll pay the freight.
http://thewholewhey.com/Item2.htm
> Hope all is well. Thanks for sharing info :)
My P is at shorts with sandals and no socks stage. :)
Little tiPs like the fructose/photocopier/cigs/etc from the
med-owl may take me down a percent or two more. :)
If I'm not happy you can remind me to smile with your own good
news of skin battles.
Will I become the chesire cat?
When Alice asked the Cheshire Cat which road she should take, he asked
her where she wanted to go.
"I really don't know. I suppose it doesn't really matter," she
replied.
"Well, then I suppose it doesn't matter what road you take," he aptly
remarked.
Or will that cat only be a smile with no P left for all to see?
randall... a real heP cat
> Matt
123matt
weird. Makes you wonder. Which road will I take? I've been off the right
road for months...even eating sweets. BUt Saturday begins my four day
fast; thereafter, there will be no sweets and I'm going to order the
wheykit. I'll be stateside for the summer beginning in late June, so I'll
have ample time/opportunity to concentrate on healing. Hey, the Land O
lakes brand--is that available all over the USA? Cost more or less than
the Wholewhey company?
Thanks...stay hep! :)
Matt
ps i'll let you know the results of the fast/cleanse
123matt
bacteria? I mean, without ordering their kit? Antibiotics? I mean, is the
enema the only way of getting rid of the bad guys that have to be
annihilated before the good whey comes in to repopulate?
Thanks, Randall!
randall
123matt wrote:
> aside from the wholewhey kit...and the enema, how does one KILL the bad
> bacteria?
By cultivation of the good bacteria. They do the job on the bad guys as
they gain mass.
How many times have I posted that photo of the good guys shooting
a blue dart in to the bad guys?
OK, i'll find it again.
http://www.sciencenews.org/articles/20020202/bob9.asp
> I mean, without ordering their kit? Antibiotics? I mean, is the
> enema the only way of getting rid of the bad guys that have to be
> annihilated before the good whey comes in to repopulate?
> Thanks, Randall!
No problem. You can take one of two options. Do the proflora
and see if you can re-stimulate the good flora on it's own or
do the wit kit implant first (re-seeds the good bugs) and then
do the proflora (sweet dairy whey) and vegetarian diet.
Chances are, if you have enough of the good stuff in the
colon, you can avoid the implant. OTOH, if you've been on antibiotics
for any length of time, the wit kit is your best bet.
I went with the implant, blew the diet, did the implant again
and saw great results within three weeks.
randall.. the answer to the above including this one ='s 4
randall
randall wrote:
Did you see this site in ____P News____ today?
http://www.med-owl.com/psoriasis/tiki-index.php
> > One level up,
> > http://www.med-owl.com/
> >
Ok, so I like this site. And I agree with his tomato/pagano page
for psoriasis. And want to go to the blue lagoon and sit
in the blue water.
---------
What else I like is the science catching uP with gut bugs.
Why shouldn't we be concerned with the lagoon right under our
nostrils?
I have a gut feeling that our salvation may very well come from this
area and they can't figure it out quick enough for me.
Here are two hits on the toPic.
What gut bug is responsible for Breaking Wind?
Every teen age boy in the world wants to know this!
What are the downstream consequences?
Read on,
http://www.nature.com/news/2006/060522/full/060522-19.html
Stomach bug makes food yield more calories
Mice with a hefty dose of a certain gut bacteria are fatter.
Helen Pearson
When you eat a cake, do you get the same calories out of it as everyone
else?
Scientists have identified a key microbe in our guts that helps us
glean more calories from food. The discovery backs the idea that the
type of microbes in our gut help to determine how much weight we gain,
and that seeding the intestine with particular bugs could help fight
obesity.
Our intestines are teeming with bacteria and other microorganisms that
help to digest the food we eat. But scientists are only just beginning
to tease out what each microbe does amidst the swarming life in these
dank, dark tubes.
Buck Samuel of Washington University in St Louis, Missouri, and his
colleagues focused on one microbe called Methanobrevibacter smithii,
which is effectively a waste-removal bug. It eats up the hydrogen and
waste products released by other microbes, and converts them into the
methane that escapes from our rear ends everyday. "It's a minor
component of the gut flora with a major impact," Samuel says tactfully.
M. smithii may have a dirty job, but Samuel and his colleagues have now
shown that it is a vital one. They found that by clearing waste
products it helps other gut bacteria digest some of the fibrous
components of food that we cannot, and turn them into material that our
bodies can use. Without these bugs, waste accumulates and blocks the
activity of other gut bacteria.
The researchers found that mice with a hefty dose of M. smithii in
their guts are fatter than those that don't have the bacteria.
Calorie counting
The discovery suggests that calorie counts on food labels could be
misleading, because different people may glean a different number of
calories from an identical banana or cheeseburger, based on the
individual mix of microbes in their gut.
.
Up to 85% of people harbour M. smithii or its cousins in their gut.
Samuel's team is now interested in examining whether overweight people
have more of this kind of bacteria, or underweight people less.
If their theory holds up in people, then it might be possible to gain
or shed pounds by planting different microbes in our guts. At this
stage, though, that is "total speculation" says Samuel.
Samuel presented the results at the American Society for Microbiology
meeting in Orlando, and will publish them shortly in the Proceedings of
the National Academy of Sciences.
Fatty acids
The researchers took mice that had been grown in a sterile environment,
with no microbes in their guts, and injected them with a very common
strain of human intestinal bacteria, called Bacteroides
thetaiotaomicron. Some of the mice also received a dose of of M.
smithii.
About 100 times more microorganisms took up residence in the colon of
mice injected with both B. theta and M. smithii than in those injected
with B. theta alone. This suggests that the presence of waste-removing
M. smithii was somehow helping other bacteria to thrive. "There's
something cool going on," Samuel says.
When both microbes were present, B. theta boosted the activity of genes
involved in breaking down and metabolizing fructans - a food
component common in onions, wheat and asparagus that the human gut
cannot digest by itself. B. theta converted the fructans into fatty
acids, some of which were taken up by the mouse gut and either used as
fuel or stored as fat.
In humans, around 10% of our calories come from such
microbe-manufactured fatty acids.
After a few weeks, mice with both types of microbe had approximately
40% more of a particular fatty acid called acetate in their blood, and
carried 15% more fat.
=======================================================
http://www.nature.com/news/2006/060529/full/060529-8.html
Baby's first microbes sized up
The bugs picked up by newborns guts could bear on later life.
Helen Pearson
Early days: researchers are starting to study how our first colony of
gut bacteria is set up.
Scientists have logged a year in the life of 14 babies' intestines, and
found that our early gut microbes bear a legacy from our very first
exposure to bugs. And this early bacterial colony could have a lasting
impact on our guts.
The study is part of intensifying interest in the microscopic organisms
crawling around our intestines. It is becoming increasingly clear that
we rely on them to help us dredge nutrients from food, fight off
invading bacteria, absorb drugs and promote healthy growth of the
immune system. Researchers who this week publish a genetic survey of
the bugs in adult digestive systems1 even go so far as to say we should
think of ourselves as 'super-organisms' made of a human-bacterial meld.
To find out how these microbial communities are first established,
David Relman at Stanford University and his colleagues collected feces
from babies on their day of birth and then regularly throughout their
first year. They also gathered samples from each mother's feces and
vagina, and her breast milk, which contains bacteria from the skin.
They extracted microbial DNA from each sample and then identified the
types of organisms present using a specially designed gene chip that
picks out hallmark genetic sequences.
The results, presented by Relman at the American Society for
Microbiology meeting in Orlando last week, indicate that babies pick up
the first microbes they meet as they enter the world. One baby's
microbes, for example, most resembled those in the mother's feces on
the day of birth; others were most similar to their mother's vaginal
sample or breast milk.
Tummy trouble
These microbe communities changed as the babies grew: as each
approached one year of age, their intestinal populations became more
alike and more like those of adults. But each baby still retained
individual microbial signatures, which were probably set up by their
unique first exposure to bugs, along with their diet and their genes.
These early events could help to mould each individual's adult
microbial population, Relman says. So anything that interferes with
this could be crucially important.
Two children in the study were given antibiotics, for example, and this
dramatically changed the natural population of microbes in their guts.
"They never returned to the picture they had before," Relman told the
meeting.
Relman says he would like to find out what factors influence a baby's
intestinal occupants. Perhaps it depends upon whether they are born by
Caesarean section or vaginally (see 'Natural birth teaches newborn gut
a lesson' ), whether a child is breast fed or formula fed, and at what
stage solid food is introduced. At the moment, the number of children
in the study is too small to answer these questions, he says.
Digestion aid
Proof of the importance of all these bugs come from a survey of adult
intestinal microbes done by Relman and others, led by Steven Gill at
the State University of New York at Buffalo. Their work, published in
Science, looks at a mass of microbial DNA extracted from the feces of
two healthy adults, and finds a disproportionate abundance of genes
involved in food digestion and processing.
The study backs the idea that microbes are important for breaking down
plant sugars that are otherwise indigestible, and making essential
amino acids and vitamins (see 'Stomach bug makes food yield more
calories' ). "They co-evolved with us to provide functions we can't
provide for ourselves," Gill says.
Researchers next want to find out how our diet and genetics influence
which microbes live within in us, and whether particular bacteria are
linked with good or ill health. They are also sampling the microbial
contents of other body cavities, including the mouth, ears and vagina
==================================================
If you like these articles. Check out their subscription opportunities
for
many areas of science,
https://secure.nature.com/subscribe/news
randall...is the P cure right under our nose? who knows? who's on 1st!
123matt
medical world to give up their billions and join us? So you don't think
Pagano is nuts? I'm going to have to rethink his diet, though. Maybe
there's a reason I naturally dislike tomatoes.
All in all, good news. Thanks for sharing. Since I haven't had
antibiotics for ages, I may try the other route for a few weeks. I'll keep
you posted.
randall
123matt wrote:
> Yes, this seems like strong evidence but how long will it take the American
> medical world to give up their billions and join us?
According to the 100th monkey principle, we create the mass and
then the old monkeys fall in line and take up the practices as if
by magic. So, if we get you to do it, we only need 98 more. lol
That will be the day. You just can't teach an old dog new tricks,
http://en.wikipedia.org/wiki/Hundredth_Monkey
But i still like the story. lol
> So you don't think
> Pagano is nuts?
He's a nut. But what kind is the question. I wish he'd show up and get
involved in the P group instead of sitting around collecting $$$ off
his book
sales....What the hell is wrong with the healers in the world?
Maybe he doesn't have computer skills or ?
> I'm going to have to rethink his diet, though. Maybe
> there's a reason I naturally dislike tomatoes.
What about the rest of the so called deadly nightshade family then?
Potatoes are
in this class. Are you turned off by them?
Lets find a link,
http://en.wikipedia.org/wiki/Nightshade
Didn't know petunias were in there.
Please don't eat the daisies!
http://en.wikipedia.org/wiki/Please_Don't_Eat_The_Daisies
A bit of trivia.
I do eat nasturtiums if i can beat the snails to em,
http://www.gardenguides.com/flowers/annuals/nasturtium.htm
The leaves have 10X's the vitamin C of lettuce!
Didn't know that i'll bet!
The flowers taste pePPery. A nice dressing of *evoo/balsamic and
juncea brassica (grey poupon) will toP off any decent salad. Yum!
*evoo- extra virgin olive oil
History of dijon,
http://perso.orange.fr/wiencis/mustard_story.html
I've been up on mustards since I read some chinese mustard thing about
blocking LPS or something,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=juncea
Oh, oh,,, don't eat potatoes that have sprouted or have a started to
get greenish
under the skin. I peel those really well, but i'm not sure if their ok
or not. But
i still eat the green ones and even a spouted one properly peeled as
well..
Guess i'm not to worried abou them...
> All in all, good news. Thanks for sharing. Since I haven't had
> antibiotics for ages, I may try the other route for a few weeks. I'll keep
> you posted.
OK...
Here's a new abstract from pubmed today.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16758223
[The significance of diet and associated factors in psoriasis.]
[Article in German]
Wolters M.
Abteilung Ernahrungsphysiologie und Humanernahrung, Institut fur
Lebensmittelwissenschaft, Zentrum Angewandte Chemie, Universitat
Hannover, Wunstorfer Strasse 14, 30453 , Hannover,
maike....@lw.uni-hannover.de.
Psoriasis is a T cell mediated inflammatory skin disease characterized
by hyperproliferation and reduced differentiation of epidermal
keratinocytes. In severe cases, the disease can result in an
insufficient nutritional status which may even be promoted by
nutrient-drug interactions. Both the general diet and single food
components have been suggested to play a role in etiology and
pathogenesis of psoriasis. Fasting periods, vegetarian diets, and diets
rich in omega-3 polyunsaturated fatty acids from fish oil have all been
associated with improvement in some studies. The most likely
explanation is the reduced amounts of _____________arachidonic
acid_________(AA) and the increased eicosapentaenoic acid (EPA) intake
resulting in a modulated eicosanoid profile. However, only one of four
controlled studies showed a benefit of omega-3 fatty acids compared to
placebo. Some psoriasis patients are gluten-sensitive and may benefit
from a gluten free diet. The active form of vitamin D exhibits
anti-proliferative and immunoregulatory effects and has been shown to
be useful in the treatment of psoriasis.
PMID: 16758223
AA has only been mentioned a few hundred times in this group,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=arachidonic+acid
http://www.google.com/search?q=arachidonic%20acid%20psoriasis&qt_s=Search&sa=N&tab=gw
Found in this last search on the web for aa and P,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10527374&dopt=Abstract
(notice-- 182 more citations for p and aa on pubmed)
Psoriasis and the arachidonic acid cascade.
Ikai K.
Department of Dermatology, Kyoto University, Graduate School of
Medicine, Japan. yu...@kuhp.kyoto-u.ac.jp
Arachidonic acid (5.8,11,14-eicosatetraenoic acid C20:4, n-6) is
released from the cell membrane by the action of phospholipases on
membrane phospholipids. Metabolites of arachidonic acid, which are
generically termed eicosanoids, including prostaglandins, thromboxane,
leukotrienes and hydroxyeicosatetraenoic acids, have been implicated as
mediators or modulators of a number of physiological functions and
pathological conditions in both normal and diseased human skin.
Particularly, eicosanoids have been suspected to play an important role
in the pathogenesis of psoriasis, because a number of phenomena
observed in psoriasis can be explained, at least in part, by the action
of eicosanoids. This review will focus on recent progress regarding the
significance of eicosanoids in the pathogenesis of psoriasis. Recent
developments in the molecular biology in the eicosanoids have renewed
interest in the role of eicosanoids in psoriasis. New understanding of
the etiology of psoriasis and advances in its treatment due to recent
progress in eicosanoid biology will also be presented.
PMID: 10527374
------------------------------------------------------------------
It's pretty cool how the abstracts come up on google and then have
all the citations listed for that search.
Once we have google mind chiPs we can all follow the science for curing
psoriasis.... lol
randall...and please don't eat the french fries... it's the oil!
randall
randall previously wrote in post #10 in this thread:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_frm/thread/3399b0e52a85ffc8/83e4d8db55f99472#83e4d8db55f99472
Special P news! My precious pet project, stays on a theme with
science to back up the FLAX.
http://www.medscape.com/viewarticle/514108
Summary
Psoriasis is considered as a T-cell-mediated inflammatory skin disease
which is characterized by hyperproliferation and poor differentiation
of epidermal keratinocytes. While susceptibility to psoriasis is
inherited, the disease is influenced by environmental factors such as
infections and stress. Diet has been suggested to play a role in the
aetiology and pathogenesis of psoriasis. Fasting periods, low-energy
diets and vegetarian diets improved psoriasis symptoms in some studies,
and diets rich in n-3 polyunsaturated fatty acids from fish oil also
showed beneficial effects. All these diets modify the polyunsaturated
fatty acid metabolism and influence the eicosanoid profile, so that
inflammatory processes are suppressed. Some patients with psoriasis
show an elevated sensitivity to gluten. In patients with IgA and/or IgG
antigliadin antibodies the symptoms have been shown to improve on a
gluten-free diet. The active form of vitamin D, 1,25-dihydroxyvitamin
D3, exhibits antiproliferative and immunoregulatory effects via the
vitamin D receptor, and thus is successfully used in the topical
treatment of psoriasis. In this review, dietary factors which play a
role in psoriasis are assessed and their potential benefit is
evaluated. Furthermore, the risk of drug-nutrient interactions in
psoriasis therapy is discussed.
<sniP>
This entire article is already posted in this group,
http://groups.google.com/groups/search?q=wolters+m+fizziwig2&qt_s=Search
Whoops. You may need to register.
http://www.medscape.com/viewarticle/514108
(9 pages long)
________________________________________________________
No matter what levels of P severity your at, you can UN-fork
inflammation
levels and lower Pasi.
Read this ANTI- inflammation article with the use of foods.
http://www.signonsandiego.com/uniontrib/20060503/news_lz1f03inflam.html
Here's more proof hot off the press for n-3's found in flax and
fish oils.
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.
Key Words: Fatty acid Ā· gene expression Ā· EPA Ā· eicosapentaenoic
acid Ā· DHA Ā· docosahexaenoic acid Ā· SREBP Ā·
sterol-responsive-element binding protein Ā· PPAR Ā· peroxisome
proliferator-activated receptor
----------------------------------------------------------------
Where is ground zero for the psoriatic then?
The gut, aka Gi tract.
So fix it and you fix your skin. I did, have and so can you!
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), visits to physicians and emergency departments
for digestive problems numbered 37.4 million and 15.2 million,
respectively, in 2003. Further, 2.5 million and 1.8 million people
sought help from health practitioners for constipation and irritable
bowel syndrome (IBS), respectively, between 2001 and 2002, according to
CDC statistics released in February 2006. Additional CDC statistics
show 70,651 men and 68,883 women were diagnosed with colorectal cancer
in 2002, one of the top 10 leading causes of death that year; and, over
a half million U.S. adults may have Crohn's disease (CD). Clearly, a
great proportion of the population suffers from various species of
gastric complaints.
Although nutritional practices and food availability have changed
drastically since antiquity, the human gastrointestinal (GI) system has
not evolved at the same rapid clip. Modern times are marked by a
simultaneous rise in GI problems and unhealthy eating patterns,
suggesting the human gut is ill-equipped to abide inflammation and
other dangers associated with the typical 21st century, Western diet.
Fortunately, proliferation of digestive ailments has created a sizeable
opportunity for manufacturers and suppliers of digestive health
products (see related story, page 38), and the modern consumer is not
immune to the influences of education and marketing.
In examining the market for such products, it helps to first understand
the digestive system's integrated physiology. Digestion begins in the
mouth, where chewing begins the mechanical breakdown and the enzyme
amylase starts the chemical process, breaking down starch into glucose
molecules. When food is swallowed, the involuntary movement of the food
through the digestive tract-an action called peristalsis-begins.
The food travels through the esophagus into the stomach, where it is
stored, mechanically mixed and chemically broken down by hydrochloric
acid and powerful enzymes. This mixture, called chyme, then travels
through the small intestine for major breakdown by enzymes excreted
from the pancreas, and nutrient absorption. At the end of this process,
the undigested portion passes into the large intestine, the home to the
majority of the body's beneficial bacteria. Generally between 400 and
500 bacterial types exist in the human digestive system, supporting
immune function and nutrient production. The large intestine absorbs
any excess water and forms the remaining material into stools for
expulsion from the colon.
Although research into the efficacy of natural GI therapies is still a
developing field, several clinical trials, reviews and other literature
suggest intake of certain compounds may promote healthy elimination,
lower inflammation and quell indigestion and other forms of distress in
the GI tract.
One such compound is dietary fiber, or nonstarch remnants of edible
plant cells including polysaccharides, lignins and associated
substances resistant to digestion by alimentary enzymes.1 Fiber can be
either soluble or insoluble, depending on its behavior in a liquid
matrix. The Physicians Desk Reference (PDR) notes soluble fiber
dissolves in water, where it forms a gel-like substance and swells,
with consequent increase in stool bulk and stimulation of peristalsis.
Consumption of soluble fiber also lowers blood cholesterol levels and
normalizes blood glucose and insulin levels.2,3 Insoluble fiber does
not absorb nor dissolve in water, and inhibits colorectal cancer,
hemorrhoids and constipation by increasing stool weight, decreasing
intestinal transit time and binding with carcinogens and mutagens.4,5
<sniP>
To find out my current suspected secret for those amazing low levels I
now enjoy, see
the fourth from last paragraph in this last link. Not the 4th from last
that's posted
but in the whole thing. You have to click it!
OK?
What? Your not ok with looking at this page?
So i'll post the rest of it right here. It's long. But worth it.
--------------------------------------------------------------------------------------
Another action of fiber is attenuation of intestinal inflammation,
thereby helping to inhibit several inflammationdriven diseases of the
digestive tract. A Spanish study conducted on rats with intestinal
inflammation showed fiber supplementation ameliorated colonic damage,
likely due to increased production of shortchain fatty acids (SCFAs),
which can work synergistically to inhibit production of proinflammatory
mediators.6 Increased SCFA production may be useful to patients with
idiopathic inflammatory bowel diseases such as CD and ulcerative
colitis, according to a review from the same institution.7
Two types of fiber consumed for their broad range of digestive benefits
are oat bran and wheat bran. In particular, both compounds are valued
for their ability to increase stool weight. A clinical trial from the
University of Wisconsin-Madison tested the different mechanisms by
which oat and wheat brans produce these effects and found bacteria and
lipids are major contributors to the increase in stool weight seen with
oat bran consumption, whereas undigested plant fiber is responsible for
much of the increase in stool weight produced by wheat bran
consumption.8
Another variety of fiber valued for its positive influence on
elimination is psyllium (Plantago ovata Forsk). According to the PDR,
the bulk of psyllium's digestive benefits are derived from the
refined xylan-rich seed husk of the plant, the component principally
used as a soluble fiber source for laxatives, ready-to-eat cereals and
nutritional supplements. Researchers from the University of Illinois,
Urbana, used a digestion simulation model to test effects of various
soluble and insoluble fibers, and speculated psyllium, due to its
particularly viscous characteristics throughout small intestinal
simulation, should be particularly effective in modulating blood
glucose and lipids.9 Other studies on psyllium have shown the compound
is particularly adept in lowering intestinal inflammation. A Spanish,
open label, parallel-group, multicenter, randomized clinical trial on
105 patients with ulcerative colitis in remission found Plantago ovata
seeds (dietary fiber) might be as effective as mesalamine to maintain
remission of the disease.10
Insoluble fiber from flax and pea, as well as the soluble fiber
glucomannan are newer fiber ingredients gaining in popularity as
treatments for constipation. Supplemental flax intake of 9.0 g/d
produced fecal bulking capacity of about 2.9 g of fecal weight/g of
fiber, according to a University of Saskatchewan study.11 The same
researchers found the addition of pea fiber to the usual diet of
elderly residents in long-term care resulted in increased stool
frequency.12 And glucomannan reduced abdominal pain and improved
constipation in a study conducted on children by scientists from the
University of Iowa.13
Certain insoluble fibers act as prebiotics, non-digestible
oligosaccharides including fructooligosaccharides (FOS), a mixture of
glucose-terminated fructose chains with a maximum length of five units,
and inulin, a long-chain, glucose-terminated polysaccharide mixture
with a partially hydrolyzed form known as oligofructose. Prebiotics
encourage proliferation of probiotics, beneficial bacteria that form
complex ecosystems in the GI tract.
In addition to boosting the population of probiotics, prebiotics have
been shown to independently generate or collaborate with probiotics to
provide many of the same effects on the digestive system as probiotics.
For example, prebiotics have been shown to prevent the symptoms of
IBD,14,15 improve bowel function by increasing stool frequency and
stool weight, and reduce the risk of certain diseases such as colon
cancer. In addition, prebiotics may support healthy digestive function
by preventing intestinal attachment of enteropathogens by acting as
receptor homologues, resulting in the suppression of harmful
microorganisms, the stimulation of probiotic growth, or both.16
Since the human digestive system has co-evolved with probiotics, it
cannot sustain proper function without these symbionts. S.K. Dash,
Ph.D., founder of UAS Laboratories, addressed the many benefits of
probiotics in A Consumer's Guide to Probiotics: "Healthpromoting
effects of beneficial bacterial include stimulation of the immune
system, reducing gas problems, improved absorption of essential
nutrients, even synthesis of vitamins.We should also note that
beneficial bacteria help us to maintain healthy cholesterol levels,
fight cancer and even promote resistance to food-borne pathogens."
According to numerous clinical trials, probiotics benefit digestive
function by breaking down lactose and producing lactic acid to help
acidify the intestinal tract; deconstructing protein to free amino
acids; and regulating peristalsis and bowel movements; thus improving
nutrient absorption.17 They also perform metabolic activities to
salvage nutrients, thus increasing absorption of calcium, copper, iron
and magnesium,18 preventing diarrhea19 and constipation.20 In the upper
digestive tract, probiotics balance bacteria levels to combat
gut-caused halitosis21 and thwart peptic ulcers through the elimination
of Helicobacter pylori bacteria in the stomach.22
Probiotics also benefit the digestive tract by helping to control
inflammatory bowel diseases, according to numerous clinical trials. In
a study conducted at the S. Raffaele University Hospital, Milan, Italy,
a cohort of 25 patients with a mild to moderate clinical flare-up of
ulcerative colitis received 250 mg of the probiotic Saccharomyces
boulardii (S. boulardii) three times per day for four weeks during
maintenance treatment with the drug mesalazine.23 Of the 24 patients
who completed the study, 17 attained endoscopically-confirmed clinical
remission of colitis.
Another branch of inflammatory bowel disease where probiotic therapy
has been established as effective is IBS. In a study conducted at the
Mayo Clinic and Mayo Foundation, Rochester, Minn., 25 patients with
Rome II IBS with predominant diarrhea were randomly assigned to receive
450 billion lyophilized probiotic bacteria or matching placebo twice
daily for eight weeks after a two-week run-in period.24 Patients were
assessed for pre- and post-treatment GI transit as well as daily bowel
function and symptoms. The scientists concluded the probiotic
supplement appeared to be promising in the relief of abdominal bloating
in patients with diarrheapredominant IBS.
Probiotics have also been shown effective in controlling the
inflammatory bowel condition pouchitis. In a study conducted at St
Mark's Hospital, London, England, 36 patients who had experienced
episodes of pouchitis at least twice in the previous year or needed
continuous antibiotics to control pouchitis, and in whom remission was
induced by four weeks of combined antibiotics therapy, were randomized
to receive probiotics (20 subjects) or placebo (16 subjects) once daily
for one year or until relapse.25 Remission was maintained for one year
in 17 patients receiving probiotics and in one patient on placebo,
while the quality of life score remained high in the probiotics group
but deteriorated in the placebo group.
Other bowel ailments where probiotics have been found helpful include
diarrhea and constipation. In a double blind study conducted on
children at the University of Buenos Aires, Argentina, 89 children with
diarrhea (caused by enteric pathogens in 40 percent of the patients)
were randomized to receive 175 g of pasteurized dairy milk containing
two viable lyophilized probiotics strains of lactobacilli and
lyophilized S. boulardii, or non-probiotic pasteurized cow milk as
placebo twice daily for a five-day period.26 Stool frequency, duration
of illness and frequency of vomiting were monitored. Lactobacilli and
S. boulardii significantly reduced stool frequency, duration of the
illness and vomiting as compared with placebo.
Similarly, at the German Institute of Human Nutrition, a double blind,
placebo-controlled, randomized study was conducted over a four-week
period in patients with chronic constipation.27 Study subjects received
65 mL/day of a beverage containing Lactobacillus casei Shirota (LcS) or
placebo. The study subjects were monitored for gastrointestinal
symptoms, well-being and stool habits and underwent a medical
examination weekly. Patients consuming LcS experienced significant
improvement in severity of constipation and stool consistency, starting
in the second week of treatment. In the final examination, 89 percent
of the LcS group and 56 percent of the placebo group reported a
positive effect of their beverage on constipation. The researchers
concluded the results of the study indicated a beneficial effect of
probiotics on gastrointestinal symptoms of patients with chronic
constipation, and the administration of probiotics may be recommended
as an adjunctive therapy for this condition.
Probiotics may also inhibit overgrowth of yeast (Candida albicans) in
the digestive tract, a condition often caused by use of antibiotics. A
pilot clinical study from Wakunaga, manufacturers of the Kyo-DophilusĀ®
line of probiotics, showed 89 percent of 36 patients infected with
Candida had lower symptom scores after taking Lactobacillus acidophilus
and Bifidobacterium bifidum (from Wakunaga). In addition, of those
supplemented, 72 percent had a greater than 25-percent improvement in
symptom scores, 33 percent had a more than 50-percent improvement in
scores, and two patients became completely symptom free after one month
without undergoing any changes in diet or other treatments.
According to research from Nebraska Cultures, L. acidophilus DDS-1 is a
particularly valuable strain as its acid, bile and alkaline stability
allow it to survive the harsh environment in the stomach and
proliferate in the intestines. The study also found L. acidophilus
DDS-1 has excellent capacity to bind to intestinal cell lines, with a
capability to displace the harmful bacterium Escherichia coli (E.
coli); the researchers noted the strain's antimicrobial activity
might help to alleviate diarrhea and other intestinal infections.
In his book, Dash suggested companies select cultures that are GRAS
(generally recognized as safe) or have been subjected to toxicological
studies prior to incorporation into products. He further noted the
culture should adhere to the intestinal walls, be proven to survive
stomach acids, and produce beneficial compounds including lactic acid,
hydrogen peroxide and natural antibiotics.
Another category of ingredients marketed for digestive health is
digestive enzymes, which combat dyspepsia and aid digestion by breaking
down food in the digestive tract. Proteases digest protein, amylases
digest carbohydrate and lipases digest fat. According to Edward Howell,
M.D., founder of National Enzyme Company (NEC), the human body relies
on food enzymes to help with digestion and cannot carry the entire load
alone; intake of exogenous enzymes from foods or supplements allows the
body to concentrate more of its energy on the activity of metabolic
enzymes.28
Digestive enzymes are often derived from porcine and bovine pancreas.
These types of enzymes, pancreatins, are of particular benefit to
patients with malabsorption syndrome due to pancreatic insufficiency.29
Animals also provide pepsin, a proteolytic enzyme produced by the
stomach.
Enzymes are also derived from plant sources. Various fruits contain
proteolytic enzymes, which are capable of digesting protein in acid,
alkaline or neutral media. Papaya contains the proteinases papain,
caricain, chymopapain and glycine endopeptidase,30 and pineapple, used
for centuries by South and Central Americans to improve digestion,31 is
a source of the enzyme bromelain. Papaya and pineapple enzymes are
thought to be particularly effective in lowering intestinal
inflammation, as they become active in higher temperatures associated
with the inflammatory response.
Certain enzymes are vulnerable to denaturation in the upper GI tract
before they can deliver benefits. A March 2006 study published in
Biochemical and Biophysical Research Communications found the four
papaya proteinases undergo, at low pH, a conformational transition that
instantaneously converts their native forms into unstable globules that
are rapidly and irreversibly degraded by pepsin; the researchers
concluded plant proteinases may require protection against both acid
denaturation and proteolysis to be effective in the gut after oral
administration.32
NEC offers Biocoreā¢, a line of enzymes including lipases designed to
target digestive problems associated with the high fat content of a
fast food diet, enzymes designed to improve assimilation of
carbohydrates, and products geared toward specific GI and digestive
conditions such as lactose intolerance. According to a proprietary
study from NEC and The Netherlands Organization for Applied Scientific
Research (TNO), a blend of fungal proteases, carbohydrases and lipases
improved digestibility and bioaccessibility of proteins and
carbohydrates in the lumen of the small intestine in
computer-controlled dynamic gastrointestinal models (TIM) of healthy
and impaired human digestion. According to the company, the study
demonstrates the value of enzyme supplementation in both healthy
individuals and those with digestive problems.
Beyond papaya and pineapple enzymes, several other botanical therapies
have been shown to support digestive health. The antioxidant
bioflavonoid quercitrin, a glycosylated form of quercetin, may protect
the GI tract from injury by stabilizing GI mast cells, which are
involved in many pathologic effects in the GI system, such as food
hypersensitivity.33 A study from Granada University in Spain showed
concurrent administration of a fish oil-, olive-oil and quercitrin-rich
diet to rats with induced colitis produced an intestinal
anti-inflammatory effect, as evidenced by a significant improvement of
all biochemical parameters of colonic inflammation assayed in
comparison with control rats.34
Another botanical thought to lower intestinal inflammation by
stabilizing mast cells is aloe vera.35 The plant's neutral
polysaccharides, aloemannan and acemannan, are responsible for some of
its anti-inflammatory effects.36 Another anti-inflammatory compound in
aloe is alprogen, which Korean research suggests inhibits histamine and
leukotriene release in mast cells activated with specific
antigen-antibody reactions.37 Aloe vera treatment can reduce leukocyte
adherence and TNF-alpha level, elevate IL-10 level and promote gastric
ulcer healing, according to a rodent study from Chulalongkorn
University, Bangkok, Thailand.38 Further, an antioxidant preparation
based on aloe vera and ubiquinol reduced intestinal inflammation,
lesions, and pathological alterations of the intestinal
electrophysiological activity and motility, in a rat model of
DSS-induced colitis.
Peppermint is another herbaceous compound known to facilitate good
digestion. Rapidly absorbed after oral administration and eliminated
mainly via the bile, menthol from the plant has a dose-dependent
antispasmodic effect on the smooth musculature of the GI tract,
interfering with the movement of calcium across cell membranes.39,40
The anti-spasmodic quality of the botanical is so effective, in fact,
that it was successfully used as a replacement for
hyoscine-N-butylbromide during upper endoscopy in a study conducted by
scientists from the University of Tokyo Graduate School of Medicine.41
According to a review from the University of Exeter in the United
Kingdom, nine randomized clinical trials involving peppermint and
dyspepsia found symptoms were reduced by peppermint in 60 to 95 percent
of patients.42
As anyone who turned to ginger ale as a child with a stomach ache
knows, there is something beneficial about ginger for the digestive
tract. A meta-analysis from Naresuan University in Phitsanulok,
Thailand, reviewed five randomized trials including 363 patients and
found a fixed dose of 1 g of ginger was more effective than placebo for
preventing postoperative nausea and vomiting.43 Similar findings on
ginger's antinausea effects were reported by Australian researchers,
who administered 1 g of ginger daily for three weeks to women (n=291)
less than 16 weeks pregnant, and found the herb reduced nausea and
vomiting.44 Taiwanese researchers speculated ginger may ameliorate
nausea by preventing development of gastric dysrhythmias and elevation
of plasma vasopressin; their theory was supported in a study of 13
volunteers with motion sickness, for whom preadministration of ginger
reduced symptoms and improved recovery after circular vection.45
In addition, basic nutrients also offer benefits in the GI field. Zinc,
for example, has proven beneficial in helping mitigate the impact of
diarrhea, particularly in children. A review from All India Institute
of Medical Sciences, New Delhi, noted zinc deficiency is common in
children from developing countries, and supplementation has been shown
to have significant benefits in preventing and treating diarrhea.46 For
example, a randomized, double blind trial in Peru involved
co-supplementation with ferrous sulfate for anemia with or without zinc
sulfate.47 Adding zinc to the iron treatment increased the hemoglobin
response and reduced diarrheal incidence compared to iron alone.
Another study conducted in two hospitals in New Delhi found
administration of zinc with rehydration therapy to children with acute
diarrhea reduced stool output and duration of illness.48 The benefits
of zinc in diarrheal treatment led researchers from the Centre for
International Health at the University of Bergen, Norway, to conclude
zinc should be included in standard case management of acute diarrhea
in developing countries as a costeffective means of enhancing standard
management of the illness.49
Zinc may also prove beneficial for Crohn's patients, who often have
low antioxidant defenses. Low serum zinc concentrations in Crohn's
sufferers are related to significantly reduced zinc absorption, even
with supplementation.50 But Italian researchers found in a study of 12
patients with Crohn's disease that supplementation with zinc sulfate
(110 mg tid) improved intestinal barrier function and helped reduce the
risk of relapse.51
Whether consumers are turning to beneficial bacteria to boost their
natural defenses, or fighting disease states with specially-formulated
nutritional products, the market for options to support
gastrointestinal health continues to grow. Examining relevant research
and determining optimal formulation and delivery options will ensure
those consumers are getting the high quality products they expect.
Click here for a full list of references for this story.
Protecting the Stomach
Given the strong enzymes and acids that work in the digestive system,
it is not surprising that one in 10 Americans develops an ulcer at some
time in his lifetime. Common causes include long-term use of
non-steroidal anti-inflammatories (NSAIDs) or bacterial infection,
generally with Helicobacter pylori (H. pylori). It is estimated that
approximately 20 percent of Americans under the age of 40 are infected
with H. pylori, and up to half of those over 60. Treatment for H.
pylori generally involves a combination of antibiotics, acid
suppressors and stomach protectors; however, a growing body of research
suggests nutritional adjuncts may prevent infection or help in the
eradication process.
Antioxidants, including vitamins A, C and E, plus carotenoids and
flavonoids, have been the focus of many studies in this area. Swedish
researchers conducted a study on dietary antioxidant levels in guinea
pigs infected with H. pylori, and found supplementation with vitamins
A, C and E and selenium reduced H. pylori infection rates and gastritis
incidence.1 Follow-up work from the group also found supplementation
with only vitamin C or astaxanthin also had an effect on infection and
gastritis, but not to the same degree. An astaxanthin-rich extract of
Haematococcus algae has proven effective at reducing gastric
inflammation associated with H. pylori infection in mice, apparently by
inhibiting lipid peroxidation and H. pylori growth.2 In vitro work has
further shown the ability of astaxanthin to protect against
NSAID-induced gastric ulcer and prevent associated increases in
oxidative damage in the gut.3 Astaxanthin also appears to work well in
combination with vitamin C, showing complementary free radical
scavenging ability as well as antimicrobial action.4
Vitamin C has been one of the primary compounds investigated for its
interaction with H. pylori. Data from 6,746 adults enrolled in the
Third National Health and Nutrition Examination Study (NHANES III) was
analyzed to determine the relationship between serum ascorbic acid and
H. pylori expression.5 The researchers found higher serum levels of
ascorbic acid were associated with a decreased incidence of H. pylori
infection, leading them to conclude ascorbic acid may positively impact
infection rate and the risk for peptic ulcer and gastric cancer.
L-carnitine, a derivative of the amino acid lysine, is more widely
known for applications in cardiovascular wellness, performance
nutrition and cognitive health. However, the compound has also been
shown to protect intestinal mucosa. Possibly due to its
antiperoxidative effects, L-carnitine significantly prevented gastric
ulcerogenesis and decreased the ulcer index in rats with
ethanol-induced mucosal injury, according to research from Trakya
University in Turkey.6 Further, a study from Sutcu Imam University
determined L-carnitine may be beneficial for patients with ulcerative
colitis.7 Treatment of rats with acetic acid caused severe damage
macroscopic and histopathological damage in the colon and significantly
increased markers of oxidative stress in colonic tissue. The
researchers observed administration of L-carnitine to the animals
improved histopathologic scores, significantly decreased
malondialdehyde and myeloperoxidase levels, prevented the depletion of
reduced glutathione levels and significantly increased superoxide
dismutase levels. Another study on L-carnitine and gastric mucosa,
conducted by scientists from Akdeniz University, found administration
of L-carnitine protected the gastric mucosa of rats with intestinal
injury induced by cold-restraint stress (CRS).8 In rats exposed to CRS,
ulcer index was higher, gastric acid production was lower, hemoglobin
leakage into the gastric lumen was increased, and gastric mucosal mucin
and PGE content were reduced, in comparison with control rats.
L-carnitine treatment prior to CRS led to attenuation of changes in
ulcer index, gastric acid secretion, hemoglobin leakage into the
gastric lumen and gastric PGE2 content.
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 GIĀ®.
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>
Side bar from this article---
Boosting Immunity Through GI Function
Beyond its core functions of extracting nutrients necessary for life
from foods and eliminating wastes, the gastrointestinal (GI) system
plays a role in immunity. Saliva and bile have antimicrobial
properties, and the pH of the stomach is fatal to most pathogens.
Further, intestinal mucosa eliminate invading pathogens and other
threats by working with lymphocytes and their products, excreting
immunoglobulins and providing a home for billions of beneficial
antipathogenic bacteria, which co-evolved with the human host.1
Disruption of the homeostasis of these bacteria interferes with signal
transduction at the epithelial cell level and may lead to inflammation
of intestinal mucosa,2 which promotes development of diseases such as
GI cancers,3 and autoimmune disorders such as Crohn's disease.4
Supplementation with probiotics may be one way to optimize immunity
through the GI tract. According to a study presented by university
researchers at the 2006 North American Research Conference on
Complementary and Integrative Medicine, ingestion of delayed release,
four-species probiotic supplement (as ImmunobiotixĀ®, from Nutraceutix)
over eight weeks produced a statistically significant increase in
percent of phagocytic peripheral blood monocytes and
polymorphonucleocytes (PMN) in healthy, non-elderly adults. Each tablet
contained a minimum of 2 x 109 organisms from four species of
probiotics, including Lactobacillus rhamnosus, Lactobacillus plantarum,
Lactobacillus salivarius a n d Bifidobacterium bifidum. Volunteers, who
had avoided use of antibiotics, probiotics or fermented foods six
months prior to the study, ingested three tablets daily for eight
weeks. Researchers monitored natural killer (NK) cell and phagocytic
activity, and levels of salivary secretory IgA at baseline and at
three, five and eight weeks. Although treatment did not significantly
increase salivary secretory IgA or NK cell activity, Increases in
percent phagocytosing cells occurred in both monocytes and PMN. The
researchers concluded ingestion of a fourspecies probiotic formulation
induces changes in immune function in healthy individuals.
__________________________________________________
Actually doing an implant of good flora and sticking to a simple plain
diet for 30 days can regrow lost benefical flora faster then any other
methods
now available in the world.
Go to www.thewholewhey.com
Get the implant kit called the wit kit and in 30 days you can look
MARVELLOUS.
http://www.radiomixshows.de/Cover%202005/CO%20Billy%20Crystal%20'You%20Look%20Marvellous'%20C1.jpg
randall... and then i'll expound on ALC!
123matt
self-enemazation process via the wholewhey so booked a few sessions for
the colon hydrotherapy plus bought good quality proflora. Couldn't find
the whey but might order that from wholewhey.com. Do you know where else
it's available? Do you think my sessions + the proflora will work as well
as the wholewhey procedure? Or close to it? Also, i read that coffee kills
the good bacteria in our bodies, but it sounds ridiculous. What do you say?
My plan isto fast during and after the colon hydratherapy and then do your
month long diet.
Hopefully...some positive results will come my way. Wish me luck...
Matt
randall
123matt wrote:
> Wow, back in the USA for a few weeks; I got nervous about the
> self-enemazation process via the wholewhey so booked a few sessions for
> the colon hydrotherapy plus bought good quality proflora. Couldn't find
> the whey but might order that from wholewhey.com.
The last person who bought the wit kit from thewholewhey.com
is nearly clear the last time I checked.
He felt it was to expensive, till after the results showed up.
Or so i'm guessing as he didn't mention the cost after that.
Getting the instructions is a good reason for buying the kit.
http://www.thewholewhey.com/Item10.htm
> Do you know where else
> it's available?
The are other products, but I really would like to have something
similar to the old one. And i'm almost due. My local health food
store said they would special order the Jay robb sweet whey for
me.
Thanks for reminding me. I'm due in the next week or so.
> Do you think my sessions + the proflora will work as well
> as the wholewhey procedure? Or close to it?
Unless you buy the stuff with the live bugs and mix it the
night before and then implant it after the colonic sessions,
you won't have the good flora going in.
> Also, i read that coffee kills
> the good bacteria in our bodies, but it sounds ridiculous.
Haven't heard that one. But three weeks on the diet
after the implant you really don't need any stimulants.
> What do you say?
> My plan isto fast during and after the colon hydratherapy and then do your
> month long diet.
What? From what i said in the group? I guess i must have. I've only
posted on it a few hundred times now. lol
> Hopefully...some positive results will come my way. Wish me luck...
Good luck. And don't forget to add the bugs and culture them with
some of the sweet whey at some temp between 80 and 100 degrees.
http://www.thewholewhey.com/Item5.htm
I didn't do this part for myself. So, i'm not totally sure. But I think
you
use all of the caps emptied in to a quart of water and you add
a cup of the sweet whey. Let them go for 24 hours in a warm spot.
Then when the last clean out is done, the implant is done on your side
and then more flat on your back and then on the other side.
Hold it in as long as possible and then the boring diet for 30 days.
Good luck again.
randall
> Matt
randall
How are you doing 123matt? It's almost a week now.
I'm about to order the jayrobb
sweet whey, unless you've found something better.
http://www.jayrobb.com/cat_SweetDairyWhey.asp
An interesting link to go along with this thread
http://www.enzymestuff.com/probiotics.htm#2
---------------------------------------------
I'm not sure if this has been posted in the P ng before.
I'll check after I post it. :)
_________________________________________________________
Big big imProvement on MTX!
Topical Mtx,
http://www.durhampharma.com/Products.htm
Durham Pharmaceuticals Ltd. has combined the medically proven systemic
drug methotrexate with the penetration enhancer AzoneĀ® to create the
first topical methotrexate product. Topical application of
Methotrexate/AzoneĀ® limits systemic exposure and consequently
systemic toxicity. Application of this product results in peak systemic
concentration levels of methotrexate that are at least 10- fold lower
than levels observed with oral administration. These lower blood
concentration levels occur while the patients treated topically are
receiving doses of methotrexate that are 50 to 100 times greater at the
site of the disease than patients receiving oral treatment. This
demonstrates that Methotrexate/AzoneĀ® significantly increases the
bioavailability of methotrexate at the disease site, while it decreases
systemic exposure, thus, greatly expanding the drug's therapeutic
window. Combining methotrexate with AzoneĀ® not only increases the
clinical utility of methotrexate by treatment via the topical route, it
will also replace many oral therapies expanding the usage of
methotrexate to other disease indications. Topical Methotrexate/AzoneĀ®
will set a precedent in the pharmaceutical industry as scientists have
tried for 20 years to develop a clinically effective topical
methotrexate product.
------------------------------------------
For all of you Mtx'ers out there. This looks state of the art.
And hoPefully you will be as WELL.
Randall.... to be CLEAR or not? What's the question!
randall
Hi,
I think I need Barry Hunt to help on this one. The skin and P are
he speciality. :)
While this looks huge, why isn't it already?
So, I had to find more on this topic. :)
Read these and see if a few questions don't jumP out
and cause you to itch your cranium or not.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8169776&dopt=Abstract
Percutaneous absorption of azone following single and multiple doses to
human volunteers.
Wester RC, Melendres J, Sedik L, Maibach HI.
Department of Dermatology, University of California, San Francisco.
Azone (1-dodecylazacycloheptan-2-one) is an agent that has been shown
to enhance percutaneous absorption of drugs. Azone is thought to act by
partitioning into skin lipid bilayers and thereby disrupting the
structure. An open-label study was done with nine volunteers (two
males, seven females; aged 51-76 years) in which Azone cream (1.6%; 100
mg) was topically dosed on a 5 x 10-cm area of the ventral forearm for
21 consecutive days. On days 1, 8, and 15, the Azone cream contained 47
microCi of [14C]Azone. The skin application site was washed with soap
and water after each 24-h dosing. Percutaneous absorption was
determined by urinary radioactivity excretion. The [14C]Azone was ring
labeled [14C-2-cyclo-heptan]. Radiochemical purity was > 98.6% and cold
Azone purity was 99%. Percutaneous absorption of the first dose (day 1)
was 1.84 +/- 1.56% (SD) of applied dose for 24-h skin application time.
Day 8 percutaneous absorption, after repeated application, increased
significantly (p < 0.002) to 2.76 +/- 1.91%. Day 15 percutaneous
absorption, after continued repeated application, stayed the same at
2.72 +/- 1.21%. In humans, repeated application of Azone results in an
initial self-absorption enhancement, probably due to its mechanism of
action. However, steady-state percutaneous absorption of Azone is
established after this initial change. Thus, Azone can enhance its own
absorption as well as that of other compounds. This should be
considered relevant for any pharmacological or toxicological
evaluation. Washing the skin site of application with soap and water
only recovered 1-2% of applied radioactivity. Previous published
studies recovered the Azone dose with ethanol washes. Thus, there could
potentially be an accumulation of Azone in skin.
PMID: 8169776
Azone with Mtx was tested back in 1998. Seems strange we haven't seen
more of it.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=2913960
Topical methotrexate therapy for psoriasis.
Weinstein GD, McCullough JL, Olsen E.
Department of Dermatology, University of California, Irvine 92717.
In vitro percutaneous penetration of methotrexate is enhanced with
1-dodecylazacycloheptan-2-one (laurocapram [Azone]).
Laurocapram-containing methotrexate formulations provide effective
local inhibition of epidermal DNA synthesis in the in vivo hairless
mouse and minipig models, providing the biochemical rationale for
topical use in the treatment of psoriasis. Topical methotrexate (0.1%,
0.5%, and 1%) in a laurocapram-containing formulation was tested in a
two-center double-blind pilot clinical study of 42 patients with plaque
psoriasis. Drugs were applied twice a day for six weeks, and lesions
were scored weekly for erythema, scale, and elevation. An overall
improvement of 50% or more in the combined scores for erythema, scale,
and elevation was obtained with 0.1% methotrexate (64% of patients),
0.5% methotrexate (59%), and 1% methotrexate (56%) vs the vehicle alone
(25%). These preliminary findings suggest that methotrexate
preparations that provide adequate percutaneous absorption may have a
beneficial effect in the treatment of psoriasis.
PMID: 2913960
Using Azone (10%-menthol) to increae CyA (CysA) absorption.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16439077
Effect of vehicles and enhancers on the topical delivery of cyclosporin
A.
Liu H, Li S, Wang Y, Yao H, Zhang Y.
School of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua RD
NO 103, Shenyang 110016, People's Republic of China.
Topical delivery of cyclosporin a (CysA) is of great interest for the
treatment of autoimmune skin disorders. The purpose of this study was
to investigate the effect of various vehicles and enhancers on the
topical delivery across rat skin. The topical (to the skin) delivery of
CysA was evaluated in vitro using rat skin mounted in a Franz diffusion
cell. CysA was analyzed by UV-HPLC. As vehicles, CysA vehicle
containing 40% ethanol showed significantly enhanced deposition of CysA
into the stratum corneum (SC) and deeper skin, as compared to other
vehicles. The efficiency of the vehicles to improve the topical
delivery of CysA was sequenced in the order of: 40% ethanol>ethyl
oleate>Transcutol>isopropyl myristate>ethanol>Labrasol>propylene
glycol>Lauroglycol FCC. Next, we tested effect of pre-treatment with
chemical enhancers on the penetration of CysA. The permeation-enhancer
effect of enhancers was in the following order: 10% menthol
approximately 0.05% SLS>5% ______Azone_____>5% NMP>5% DEMO. Moreover,
chemical enhancers shortened the lag time of the penetration of CysA
into deeper skin. The present study suggests that the suspension of 40%
ethanol containing 0.5% drug can more effectively enhance the topical
delivery of CysA after skin pre-treatment with 10% menthol or 0.05%
SLS.
PMID: 16439077
------------------------------------------------------------------------------
Could the large Pharms be boycotting Durham for some take over
strategy or something? Or could DMSO be used for free without
having to pay someone?
A cream Mtx put directly in to the patch without screwing uP the liver
cells,
seems rather ideal to me.
Heck i would be willing to cream a patch of plaque now and then in
blue periods.
So?
randall... ask your derm for this stuff. for grins
randall
How would you like to have some rather mundane disease like RA
(rheumatoid arthritis), be treated with biologicals and
end up with psoriasis? IT HAPPENS!
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16821276
Anti-Tumor Necrosis Factor-a-Induced Psoriasis.
Sari I, Akar S, Birlik M, Sis B, Onen F, Akkoc N.
>From the Department of Internal Medicine, Division of Rheumatology, and
Department of Pathology, Dokuz Eylul University School of Medicine,
Izmir, Turkey.
We describe a patient with rheumatoid arthritis who developed psoriasis
during treatment with etanercept; psoriatic lesions resolved completely
after the drug was discontinued, but returned on rechallenge. No such
adverse skin reaction occurred after switching therapy to infliximab.
Through a Medline search we identified 11 reports involving 32 patients
who developed psoriasis/psoriasiform eruptions during therapy with
tumor necrosis factor-alpha (TNF-alpha) inhibitors. All TNF-alpha
blocking agents have been reported to lead to or exacerbate psoriasis.
In some cases skin changes were severe enough to discontinue the
medication.
PMID: 16821276
-----------------------------------------------------------------------
Physalis peruviana- aka cape gooseberry,
http://www.tradewindsfruit.com/cape_gooseberry.htm
Taste sounds ok.
Eat these critters and clear up?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16820275
Supercritical carbon dioxide extract exhibits enhanced antioxidant and
anti-inflammatory activities of Physalis peruviana.
Wu SJ, Tsai JY, Chang SP, Lin DL, Wang SS, Huang SN, Ng LT.
Department of Health and Nutrition, Chia-Nan University of Pharmacy and
Technology, Tainan, Taiwan.
Physalis peruviana L. (PP) is a medicinal herb widely used in folk
medicine. In this study, supercritical carbon dioxide (SFE-CO(2))
method was employed to obtain three different PP extracts, namely
SCEPP-0, SCEPP-4 and SCEPP-5. The total flavonoid and phenol
concentrations, as well as antioxidant and anti-inflammatory activities
of these extracts were analyzed and compared with aqueous and ethanolic
PP extracts. Among all the extracts tested, SCEPP-5 demonstrated the
highest total flavonoid (234.63+/-9.61mg/g) and phenol
(90.80+/-2.21mg/g) contents. At concentrations 0.1-30mug/ml, SCEPP-5
also demonstrated the strongest superoxide anion scavenging activity
and xanthine oxidase inhibitory effect. At 30mug/ml, SCEPP-5
significantly prevented lipopolysaccharide (LPS; 1mug/ml)-induced cell
cytotoxicity in murine macrophage (Raw 264.7) cells. At 10-50mug/ml, it
also significantly inhibited LPS-induced NO release and PGE(2)
formation in a dose-dependent pattern. SCEPP-5 at 30mug/ml remarkably
blocked the LPS induction of inducible nitric oxide synthase (iNOS) and
cyclooxygenase-2 (COX-2) expression. Taken together, these results
suggest that SCEPP-5, an extract of SFE-CO(2), displayed the strongest
antioxidant and anti-inflammatory activities as compared to other
extracts. Its protection against LPS-induced inflammation could be
through the inhibition of iNOS and COX-2 expression.
PMID: 16820275
More helpful pathways from curcumin.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16820944
[...]
Moreover, elevated hepatic levels of TNF-alpha and IL-1beta post-CLP
were decreased by curcumin pre-treatment. This reduction was associated
with increased expression of AhR and CYP1A2. These results indicate
that KCs-derived proinflammatory cytokines may play an important role
in downregulating CYP1A2 in sepsis. The reduction of AhR/Arnt may be
the underlying mechanism for such downregulation. Inhibition of
proinflammatory cytokines by curcumin may provide a novel approach to
modulate the hepatic CYP function in sepsis.
PMID: 16820944
===========================================================
This next one could be BIG.
Wow, wow, wow. For anyone with gluten problems and psoriasis.
http://www.medicalnewstoday.com/medicalnews.php?newsid=46446&nfid=nl
A new enzyme originally developed for commercial food processing turns
out to also quickly and nearly-completely break down whole gluten
molecules as well as the T cell stimulatory peptides that cause celiac
disease, a digestive disease with no current effective treatment other
than avoiding wheat, barley or rye products.
In addition, the enzyme operates best in just the kind of physiological
environment found in the human stomach and works 60 times faster than
an earlier promising enzyme, which was not effective in acidic
conditions and was inactivated by pepsin, both of which are found in
the stomach.
"On the basis of our results, there now is a realistic chance that oral
supplementation with an enzyme can ensure gluten degradation in the
stomach before reaching the small intestine, where it causes problems
for people with celiac disease," according to Frits Koning, researcher
at the Leiden University Medical Center, The Netherlands, who headed
the team that has published a new research paper on its work.
The paper, "Highly efficient gluten degradation with a newly identified
prolyl endoprotease: implications for celiac disease," is in the online
American Journal of Physiology- Gastrointestinal and Liver Physiology,
published by The American Physiological Society. Research was by
Dariusz Stepniak, Liesbeth Spaenij-Dekking, Cristina Mitea, Martine
Moester, Arnoud de Ru, Renee Baak-Pablo, Peter van Veelen and Frits
Koning of Leiden University Medical Center, the Netherlands, and Luppo
Edens of DSM Food Specialties, Delft.
Clinical trials are likely next step
The new prolyl endoprotease (PEP) that was studied is derived from
Aspergillus niger (AN), a common fungus. Strains of A. niger are used
in industrial production of citric and gluconic acid as well as
producing several food grade enzymes.
Because there are no animal models of celiac disease, "the in vivo
efficacy of AN-PEP for gluten detoxification will ultimately have to be
addressed in clinical studies involving celiac patients. AN-PEP appears
to be a prime candidate for such clinical trials," the paper concluded.
As for the timing of any such trials, Koning said: "This is an option
the team hopes to explore in the future."
A disease of many paradoxes
Celiac disease affects about 2 million Americans and is also found in
Europe, India and parts of the Middle East. It's caused by an
uncontrolled immune response to wheat gluten and similar proteins of
rye and barley that cause diarrhea, malnutrition and failure to thrive
because it inhibits nutritional uptake.
"It's a Caucasian disease with a wide spectrum of symptoms; not all
patients are equally affected, but we do not understand why this is the
case," Koning said. "It is known to be associated with the HLA-DQ2
gene," he noted, "but while about 25% of the white population has this
gene, only about one in 100 get the disease, so it's really a quite
puzzling disease in many ways."
Currently the only way to elude the disease symptoms is by avoiding
wheat, barley and rye products. "It sounds easy, but gluten especially
is widespread in Western diets," Koning said. Gluten is often used as a
food additive because it adds protein content inexpensively and also
gives dough its elasticity and stickiness, which helps in
manufacturing. For instance, Koning said: "Celiac patients can eat
potato chips, but not if they have added paprika or other spices
because they're 'glued' to the chip with gluten."
AN-PEP outstrips earlier enzyme by 60-fold
Earlier attempts at finding non-human proteases for gluten
detoxification (first proposed in the late 1950s) focused on prolyl
oligopeptidases (POP), most notably FM-POP, which was able to break
down gluten sequences in vitro. However FM-POP's optimal operating pH
is between 7 and 8, so it didn't work well in the more acidic stomach
pH that goes down to 2 at one stage. A combination of pH 2 and pepsin
"immediately inactivated FM-POP," the paper said. AN-PEP, on the other
hand, is active from pH 2-8, with optimum effect around pH 4. The
combination of pH 2 and pepsin didn't affect AN-PEP activity.
"An effective enzymatic treatment for celiac diseases requires means of
destroying all or at least the vast majority of gluten derived T cell
stimulatory sequences," the paper said. The key to this is to break the
large gluten molecules (large peptides and intact proteins) into
smaller pieces before they leave the stomach. Because food stays in the
stomach one to four hours, speed of protein degradation is also
important. Mass spectrometry comparisons showed that "degradation of
gluten peptides by AN-PEP was on average [about 4 minutes, or] 60 times
faster than degradation by FM-POP," the paper reported.
In addition to its ability to perform as a potential oral enzymatic
therapy because it "is capable of degrading intact gluten molecules and
T cell stimulatory epitopes from gluten into harmless fragments" AN-PEP
has several additional commercial advantages, the paper said: "The
enzyme is extremely stable and can be produced at acceptable cost at
food grade quality in an industry setting."
Celiac disease is an HLA-linked disease related to Type 1 diabetes and
rheumatoid arthritis in which autoimmune reactions cause the disease;
similarly, immune reactions can lead to organ transplant rejection.
Koning said it "isn't likely that AN-PEP would be of any therapeutic
value in any of these HLA-associated diseases" because Type 1 diabetes
and rheumatoid arthritis are real autoimmune diseases, where the immune
system attacks parts of the body. In celiac disease, it is the gluten
that is the target, not the body.
Reminder warning on early introduction of gluten products
Koning said feeding wheat (or barley or rye) products to infants before
they're 6 months old isn't recommended because once an immune response
develops "immuno-memory builds up and it doesn't go away." Indeed,
Koning noted that in Sweden some years ago gluten was introduced into
baby food, which led to a five-fold increase in celiac disease. The
problem disappeared when gluten was removed.
###
Source and funding/support
The paper, "Highly efficient gluten degradation with a newly identified
prolyl endoprotease: implications for celiac disease," is in the online
American Journal of Physiology-Gastrointestinal and Liver Physiology,
published by The American Physiological Society. Research was by
Dariusz Stepniak, Liesbeth Spaenij-Dekking, Cristina Mitea, Martine
Moester, Arnoud de Ru, Renee Baak-Pablo, Peter van Veelen and Frits
Koning, Department of Immunohematology and Blood Transfusion, Leiden
University Medical Center, Leiden, the Netherlands, and Luppo Edens of
DSM Food Specialties, Delft, a subsidiary of Koninklijke DSM N.V., a
Dutch chemical conglomerate.
Research supported by Netherlands Organization for Scientific Research,
Celiac Disease Consortium, Centre for Medical Systems Biology (the
latter two partly backed by the Netherlands Genomics Initiative). DSM
supplied A. niger-derived PEP (AN-PEP) on which it holds a patent.
The American Physiological Society was founded in 1887 to foster basic
and applied bioscience. The Bethesda, Maryland-based society has more
than 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 2004,
APS received the Presidential Award for Excellence in Science,
Mathematics and Engineering Mentoring (PAESMEM).
Contact: Mayer Resnick
============================================
What's the difference between you and anyone else who gets UVB's?
http://www.medicalnewstoday.com/medicalnews.php?newsid=46746&nfid=nl
Like a bodyguard turned traitor, a protein whose regular job is to help
repair severed DNA molecules will, in some cases, join forces with
another protein to do the opposite and chop the DNA to bits, according
to new research at the University of Minnesota. The chopping up of a
cell's DNA occurs in response to damage, for example, from ultraviolet
light, and appears to be a means of killing the cell before it can
become dysfunctional or cancerous. The proteins are produced by two
cellular processes, both of which must be set in motion before the
proteins can gang up on the DNA molecule and seal the cell's fate. The
researchers describe their discovery in the July 7 issue of Archives of
Internal Medicine.
The self-killing of cells is termed apoptosis, and its purposes include
not only culling damaged cells but shaping an embryo by getting rid of
webbing tissue between fingers and toes. By contributing to the
understanding of how apoptosis works, the researchers, led by Zigang
Dong of the university's Hormel Institute in Austin, Minn., hope
someday to see the process used to kill cancer cells or other unwanted
tissue.
The "bodyguard" protein belongs to a class of proteins called histones,
which act like spools for the "thread" of DNA molecules. Rather than
float in the cell nucleus like an overlong piece of spaghetti, the DNA
molecule loops around regularly spaced histones, which not only support
the DNA but play various roles in managing its functions.
"In the past, people thought histones were just for packaging DNA,"
said Dong, who studied a histone named H2AX. "People believe H2AX plays
a role in DNA repair. But we find that if DNA can't be repaired, the
cell undergoes apoptosis. The histone H2AX is probably important for
both apoptosis and DNA repair."
Dong and his colleagues were led to the discovery by their previous
work on the biochemistry of skin cancer. They had previously found that
various forms of an enzyme known as JNK played a role in the
development of the cancer. Working with cells from the skin of mice,
they have now discovered that after they expose cells to damaging
amounts of ultraviolet light, a form of JNK initiates both of the
cellular processes that culminate in DNA destruction.
In one process, JNK starts a chain reaction that leads to the
activation of an enzyme that chops up DNA. In the other process, JNK
activates the histone H2AX. The activated enzyme and the activated
histone work together to make mincemeat of the DNA. Dong and his
colleagues are the first to show that activation of H2AX is necessary
for apoptosis to occur by means of the DNA-chopping enzyme. The work
was supported by the Hormel Foundation and the National Institutes of
Health.
-----------------------------------------------------------
SEX differences in disease. Could be another biggy for psoriasis.
http://www.medicalnewstoday.com/medicalnews.php?newsid=46763&nfid=nl
UCLA researchers report that thousands of genes behave differently in
the same organs of males and females - something never detected to this
degree. Published in the August issue of Genome Research, the study
sheds light on why the same disease often strikes males and females
differently, and why the genders may respond differently to the same
drug.
"We previously had no good understanding of why the sexes vary in
their relationship to different diseases," explained Xia Yang, Ph.D.,
first author and postdoctoral fellow in cardiology at the David Geffen
School of Medicine at UCLA. "Our study discovered a genetic disparity
that may explain why males and females diverge in terms of disease
risk, rate and severity."
"This research holds important implications for understanding
disorders such as diabetes, heart disease and obesity, and identifies
targets for the development of gender-specific therapies," said Jake
Lusis, Ph.D., co-investigator and UCLA professor of human genetics.
The UCLA team examined brain, liver, fat and muscle tissue from mice
with the goal of finding genetic clues related to mental illnesses,
diabetes, obesity and atherosclerosis. Humans and mice share 99 percent
of their genes.
The scientists focused on gene expression -- the process by which a
gene's DNA sequence is converted into cellular proteins. With the help
of Rosetta Informatics, the team scrutinized more than 23,000 genes to
measure their expression level in male and female tissue.
What they found surprised them. While each gene functioned the same in
both sexes, the scientists found a direct correlation between gender
and the amount of gene expressed.
"We saw striking and measurable differences in more than half of the
genes' expression patterns between males and females," said Dr.
Thomas Drake, co-investigator and UCLA professor of pathology. "We
didn't expect that. No one has previously demonstrated this genetic
gender gap at such high levels."
UCLA is the first to uncover a gender difference in gene expression in
fat and muscle tissue. Earlier studies have identified roughly 1,000
sex-biased genes in the liver, and other research has found a combined
total of 60 gender-influenced genes in the brain - about one-tenth of
what the UCLA team discovered in these organs.
Even in the same organ, the researchers identified scores of genes that
varied in expression levels between the sexes. Gender consistently
influenced the expression levels of thousands of genes in the liver,
fat and muscle tissue. This effect was slightly more limited in the
brain, where hundreds, not thousands, of genes showed different
expression patterns.
"Males and females share the same genetic code, but our findings
imply that gender regulates how quickly the body can convert DNA to
proteins," said Yang. "This suggests that gender influences how
disease develops."
The gender differences in gene expression also varied by tissue.
Affected genes were typically those most involved in the organ's
function, suggesting that gender influences important genes with
specialized roles, not the rank-and-file.
In the liver, for example, the expression of genes involved in drug
metabolism differed by sex. The findings imply that male and female
livers function the same, but work at different rates.
"Our findings in the liver may explain why men and women respond
differently to the same drug," noted Lusis. "Studies show that
aspirin is more effective at preventing heart attack in men than women.
One gender may metabolize the drug faster, leaving too little of the
medication in the system to produce an effect."
"At the genetic level, the only difference between the genders is the
sex chromosomes," said Drake. "Out of the more than 30,000 genes
that make up the human genome, the X and Y chromosomes account for less
than 2 percent of the body's genes. But when we looked at the gene
expression in these four tissues, more than half of the genes differed
significantly between the sexes. The differences were not related to
reproductive systems - they were visible across the board and related
to primary functions of a wide variety of organs."
The UCLA findings support the importance of gender-specific clinical
trials. Most medication dosages for women have been based on clinical
trials primarily conducted on men.
"This research represents a significant step forward in deepening our
understanding of gender-based differences in medicine," said Dr.
Janet Pregler, director of the Iris Cantor-UCLA Women's Health Center.
The center's executive advisory board, a group of businesswomen
interested in advancing women's health, helped fund the study.
"Many of the genes we identified relate to processes that influence
common diseases," said Yang. "This is crucial, because once we
understand the gender gap in these disease mechanisms, we can create
new strategies for designing and testing new sex-specific drugs."
The National Institute for Heart, Lung and Blood; the National
Institute of Diabetes and Digestive and Kidney Diseases; and the UCLA
National Center for Excellence in Women's Health also supported the
study. Coauthors included Susanna Wang, Leslie Ingram-Drake and Arthur
Arnold, all from UCLA, and Eric Schadt of Rosetta Inpharmatics, a
subsidiary of Merck and Co.
___________________________________________________
Just can't get away from adenosine these days,
http://www.medicalnewstoday.com/medicalnews.php?newsid=46557&nfid=nl
Adenosine, long known to be a regulator of heart function, has recently
been identified as an inhibitor of inflammation that acts primarily by
activating the A2A adenosine receptor (A2AAR) on lymphoid and myeloid
cells. In a study appearing in the July issue of the Journal of
Clinical Investigation, Katya Ravid and colleagues from Boston
University School of Medicine show that deletion of the gene encoding
the A2B adenosine receptor (A2BAR) in mice triggers inflammation. This
suggests that activation of A2BARs, particularly those present on
macrophages, can have anti-inflammatory effects.
In an accompanying commentary Joel Linden from The University of
Virginia explores these results, highlighting that the role of A2BAR
remains enigmatic because its activation can either stimulate or
inhibit the release of proinflammatory molecules in different cells and
tissues.
TITLE: The A2B adenosine receptor protects against inflammation and
excessive vascular adhesion
AUTHOR CONTACT:
Katya Ravid
Boston University School of Medicine, Boston, Massachusetts, USA.
E-mail: ra...@biochem.bumc.bu.edu.
View the PDF of this article at:
http://https://www.the-jci.org/article.php?id=27933
AUTHOR CONTACT:
Joel Linden
University of Virginia, Charlottesville, Virginia, USA.
Email: jli...@virginia.edu.
View the PDF of this article at:
http://https://www.the-jci.org/article.php?id=29125
------------------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=46860&nfid=nl
Centenary scientist Associate Professor Barbara Fazekas de St. Groth, a
leader in inflammatory bowel disease research, has demonstrated for the
first time the important role of T cells in the prevention of
autoimmune diseases in humans.
In a study involving 38 patients with Crohn's disease and ulcerative
colitis, the two common forms of inflammatory bowel disease (IBD), and
43 healthy controls, Assoc Prof Fazekas and colleagues found that
healthy individuals have up to twice the number of disease-fighting
regulatory T cells compared with IBD patients at the onset of disease.
"It is important to have more regulatory T cells, especially when you
are young, as individuals with a deficiency are more susceptible to
disease and frequency of disease is higher in the young," says Assoc
Prof Fazekas.
"Our results also indicate that the activity of these cells is
increased in IBD patients during the later stages of disease in an
attempt to fight it."
IBD is usually diagnosed in children and young adults. It affects 1 in
200 people and an estimated 100,000 Australians and there is no cure.
"Regulatory T cells have previously been difficult to quantify in
humans and conventional methods could identify fewer than a third of
the total number. The blood test we have developed allows us for the
first time to accurately count the number of regulatory T cells in the
body," says Assoc Prof Fazekas.
The highly accurate identification and isolation of regulatory T cells
was made possible using sophisticated flow cytometry equipment at the
Centenary Institute.
The machines use laser beams and advanced optics and electronics to
analyse and purify many kinds of cells at a rate of over 25,000 cells
every second. This technology is able to produce results that cannot be
obtained by any other method as it allows every cell to be identified
and sorted on an individual basis.
"The ability to detect regulatory T cell deficits in inflammatory
diseases such as IBD means that we can now identify individuals at risk
of developing disease. The test can also be used to assess the effect
of new preventative treatments in the future."
The researchers are using the test to study regulatory T cell levels in
autoimmune, inflammatory and allergic diseases such as multiple
sclerosis, Type 1 diabetes, rheumatoid arthritis, asthma and eczema, to
determine the risk of disease in patients and their families.
###
The research was done in collaboration with the Centre for Immunology
at St Vincent's Hospital, and the Royal Prince Alfred and Nepean
Hospitals.
The study will be published in the July issue of The Journal of
Experimental Medicine.
====================================================
Kick the crap outa the crap in your gums with crainberries.
http://www.medicalnewstoday.com/medicalnews.php?newsid=46874&nfid=nl
====================================================
Warning::: P GENES P genes,
The P gene still doesn't want to come out of the skin!
Darn P genie is stuck. The latest,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16829306
A Role for KIR Gene Variants Other Than KIR2DS1 in Conferring
Susceptibility to Psoriasis.
Ploski R, Luszczek W, Kusnierczyk P, Nockowski P, Cislo M, Krajewski P,
Malejczyk J.
Department of Medical Genetics, Medical University in Warsaw, Warsaw,
Poland.
Recently we described an association between psoriasis and KIR2DS1, a
gene for a stimulatory natural killer cell receptor, in a Polish
population. The association was independently reported among Japanese
and confirmed in a U.S. population. Prompted by these findings, we
reanalyzed data by a multivariate approach in search of possible
effects of KIR genes other than KIR2DS1 (non-KIR2DS1). The methodology
was based on a stratified analysis and multiple logistic regression. We
found that the non-KIR2DS1 genes had joint effects comparable to or
stronger than the effects of KIR2DS1 in both the fraction of explained
variance (0.174 vs 0.204, respectively, for KIR2DS1 and non-KIR2DS1)
and the statistical significance (p = 0.000008 vs p = 0.000001,
respectively). When individual genes were considered, a decrease in
KIR2DS5 among patients vs controls (OR = 0.2, p(cor) = 0.0005) and a
decrease in KIR2DS3 restricted to KIR2DS1-positive individuals (OR =
0.2, p(cor) = 0.005) were evident. We also performed a multivariate
analysis of the HLA-Cw genotypes but failed to demonstrate any effects
in addition to the known association with HLA-Cw*06. We conclude that
the effect of the KIR genes on psoriasis susceptibility is complex,
extending beyond the association with KIR2DS1 and involving protective
effects and interactions.
PMID: 16829306
http://www.ncbi.nlm.nih.gov/gquery/gquery.fcgi?term=+KIR2DS1
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600164
http://groups.google.com/groups/search?q=+KIR2DS1&qt_s=Search
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM&cmd=search&term=KIR2DS1
==============================================================
Some sugar for p,
(this topic is in the P ng already. keyword:: Immucillin )
http://www.rsc.org/Publishing/ChemicalBiology/Volume/2006/3/Unnatural_sugar_enantiomers_join_fight_against_disease.asp
[...]
Keith Clinch from Industrial Research Limited, New Zealand, and
colleagues have prepared the L-nucleoside analogues of two D-nucleoside
pharmaceuticals currently undergoing clinical trials in order to try to
find new drugs.
L-enantiomer of immucillin-H against leukemia
Immucillin-H is in Phase II trials as an anti-leukaemia agent and
DADMe-Immucillin-H is in Phase I trials as an anti-psoriasis drug. The
L-enantiomers of these drugs were prepared and tested as enzyme
inhibitors by their ability to bind the enzyme purine nucleoside
phosphorylase (PNPase). The human and bovine forms of the PNPases were
tested and compared with those obtained for the original, D-nucleoside
forms of the drugs.
Despite being less active than the D-enantiomer, the L-enantiomer of
Immucillin-H was still potent. L-Immucillin-H was found to be more
active than some analogues of D-Immucillin-H as an inhibitor of the
human PNPase enzyme. L-DADMe-Immucillin-H proved to be quite potent as
a sub-nanomolar inhibitor against human and bovine PNPase enzymes.
Interest in these compounds has increased as they too have the
potential to become pharmaceutical products.
<sniP>
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16525558
Syntheses and bio-activities of the L-enantiomers of two potent
transition state analogue inhibitors of purine nucleoside
phosphorylases.
Clinch K, Evans GB, Fleet GW, Furneaux RH, Johnson SW, Lenz DH, Mee SP,
Rands PR, Schramm VL, Taylor Ringia EA, Tyler PC.
Carbohydrate Chemistry Team, Industrial Research Limited, P.O. Box
31310, Lower Hutt, New Zealand. k.cl...@irl.cri.nz
(1R)-1-(9-Deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-L-ribitol
[(+)-5] and
(3S,4S)-1-[(9-deazahypoxanthin-9-yl)methyl]-4-(hydroxymethyl)pyrrolidin-3-ol
[(-)-6] are the L-enantiomers of immucillin-H (D-ImmH) and
DADMe-immucillin-H (D-DADMe-ImmH), respectively, these D-isomers being
high affinity transition state analogue inhibitors of purine nucleoside
phosphorylases (PNPases) developed as potential pharmaceuticals against
diseases involving irregular activation of T-cells. The C-nucleoside
hydrochloride D-ImmH [(-)-5) x HCl], now "Fodosine" is in phase II
clinical trials as an anti-T-cell leukaemia agent, while D-DADMe-ImmH
is a second generation inhibitor with extreme binding to the target
enzyme and has entered the clinic for phase I testing as an
anti-psoriasis drug. Since the enantiomers of some pharmaceuticals have
revealed surprising biological activities, the L-nucleoside analogues
(+)-5 x HCl and (-)-6, respectively, of D-ImmH and D-DADMe-ImmH, were
prepared and their PNPase binding properties were studied. For the
synthesis of compound (-)-6 suitable enzyme-based routes to the
enantiomerically pure starting material
(3S,4S)-4-(hydroxymethyl)pyrrolidin-3-ol [(-)-6] and its enantiomer
were developed. The L-enantiomers (+)-5 x HCl and (-)-6 bind to the
PNPases approximately 5- to 600-times less well than do the
D-compounds, but nevertheless remain powerful inhibitors with nanomolar
dissociation constants.
PMID: 16525558
Transition states and inhibitors of the purine nucleoside phosphorylase
family.
Taylor Ringia EA, Schramm VL.
Department of Biochemistry, Albert Einstein College of Medicine of the
Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Purine nucleoside phosphorylase (PNP), an enzyme involved in the
catabolism and recycling of nucleosides, is under investigation for the
development of novel antibiotics. One method used for the design of
inhibitors is transition state analysis. Chemically stable analogues of
a transition state complex are predicted to convert the energy of
enzymatic rate acceleration (kcat/k(non)) into binding energy.
Transition state structures have been reported for the bovine (Bos
taurus), human (Homo sapiens), and malarial (Plasmodium falciparum)
PNPs. All three enzymes proceed through S(N)1-like mechanisms and have
transition states with substantial ribooxocarbenium ion character.
Bovine PNP proceeds through an early S(N)1-like transition state,
whereas the human and malarial PNPs proceed through more dissociative
transition state. Transition state analogues developed for PNP exhibit
differential inhibition specificity for these three enzymes based upon
their distinct reaction rates (kcat), mechanisms, and substrate
specificity. The most powerful inhibitors of these three enzymes have
picomolar dissociation constants, two of which are Immucillin-H and
DADMe-Immucillin-H. MT-Immucillin-H was also developed as a specific
inhibitor for P. falciparum PNP by virtue of its unique utilization of
5'-methylthio substrates. Although the transition state for
tuberculosis (Mycobacterium tuberculosis) PNP is yet to be determined,
inhibition values support a mechanism with a dissociative transition
state like those of its human and plasmodial counterparts. Comparison
of the transition states and substrate specificity of various PNPs
permits the design of species-specific inhibitors for use as
therapeutic agents.
PMID: 16305529
Energetic mapping of transition state analogue interactions with human
and Plasmodium falciparum purine nucleoside phosphorylases.
Lewandowicz A, Ringia EA, Ting LM, Kim K, Tyler PC, Evans GB, Zubkova
OV, Mee S, Painter GF, Lenz DH, Furneaux RH, Schramm VL.
Department of Biochemistry, Albert Einstein College of Medicine, Bronx,
New York 10461, USA.
Human purine nucleoside phosphorylase (huPNP) is essential for human
T-cell division by removing deoxyguanosine and preventing dGTP
imbalance. Plasmodium falciparum expresses a distinct PNP (PfPNP) with
a unique substrate specificity that includes 5'-methylthioinosine. The
PfPNP functions both in purine salvage and in recycling purine groups
from the polyamine synthetic pathway. Immucillin-H is an inhibitor of
both huPNP and PfPNPs. It kills activated human T-cells and induces
purine-less death in P. falciparum. Immucillin-H is a transition state
analogue designed to mimic the early transition state of bovine PNP.
The DADMe-Immucillins are second generation transition state analogues
designed to match the fully dissociated transition states of huPNP and
PfPNP. Immucillins, DADMe-Immucillins and related analogues are
compared for their energetic interactions with human and P. falciparum
PNPs. Immucillin-H and DADMe-Immucillin-H are 860 and 500 pM inhibitors
against P. falciparum PNP but bind human PNP 15-35 times more tightly.
This common pattern is a result of kcat for huPNP being 18-fold greater
than kcat for PfPNP. This energetic binding difference between huPNP
and PfPNP supports the k(chem)/kcat binding argument for transition
state analogues. Preferential PfPNP inhibition is gained in the
Immucillins by 5'-methylthio substitution which exploits the unique
substrate specificity of PfPNP. Human PNP achieves part of its
catalytic potential from 5'-OH neighboring group participation. When
PfPNP acts on 5'-methylthioinosine, this interaction is not possible.
Compensation for the 5'-OH effect in the P. falciparum enzyme is
provided by improved leaving group interactions with Asp206 as a
general acid compared with Asn at this position in huPNP. Specific
atomic modifications in the transition state analogues cause
disproportionate binding differences between huPNP and PfPNPs and
pinpoint energetic binding differences despite similar transition
states.
PMID: 15961383
http://www.jbc.org/cgi/content/full/jbc;280/34/30320
&
http://www.pnas.org/cgi/content/full/98/8/4593
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=11444966&dopt=Citation
------
This is a Hector DeLuca company. He's that prof from
UW who is the genius of vitamin D.
http://www.quatrx.com/clinical/beco.htm
Becocalcidiol
Becocalcidiol is our product candidate for the treatment of mild to
moderate psoriasis. Becocalcidiol is a novel topical calcitriol
(vitamin D) analogue. Topical selective calcitriol and its analogues
have been shown for many years to be effective in the treatment of
psoriasis. Based on our completed Phase IIb study, becocalcidiol was
statistically superior to vehicle in reducing plaque and did not result
in excessive blood calcium levels, a side effect of existing calcitriol
topical treatments for psoriasis. This allows the potential for use of
becocalcidiol at higher doses and/or on larger body surface areas than
can be achieved with existing calcitriol topical products. We believe
that the ability to treat patients with higher doses may in turn offer
the potential for enhanced efficacy. In our clinical and preclinical
studies, becocalcidiol has been well tolerated with a low incidence of
skin irritation.
-----------------------
Randall.... ok, i know, this thing doesn't want to end!
randall
Special NEWS flash.
http://www.scientistlive.com/15895/gene-for-depression-discovered.thtml
GENE FOR DEPRESSION DISCOVERED
In a significant break-through, researchers identify P2RX7 as the gene
responsible for major depressive disorders and, surprisingly, find it
has no link with serotonin.
It has been known for many years that genetic factors are at the base
of depression and bipolar disorder, but the complex molecular networks
involved remain unknown.
"The actual gene, known as P2RX7, is found in humans and animals and
is responsible for depression. It has taken many years to find," said
neuroscientist, Professor Barden from CHUL Research Centre in Quebec,
speaking at the Forum of European Neuroscience. Finding it is highly
significant in uncovering the molecular pathways involved in
depression.
The results were published in May 2006 American Journal of Medical
Genetics.
During their lifetime, about 5-12 per cent of men and 10-25 pre cent of
women will experience at least one episode of major depression. People
with bipolar disorder - also known as manic depression - experience
extreme mood swings.
Depression has until now often been associated with the serotonin
system in the brain, a system that can influence mood and emotion.
"What is particularly exciting is that P2RX7 has nothing to do with
serotonin," said Professor Barden. Drugs that boost the flow of
serotonin can be effective anti-depressants, but take weeks to take
effect. The fact that P2RX7 that has nothing to do with serotonin could
partly explain why.
Animal studies have shown that this gene is expressed in brain areas
known to be involved in depression, and depressive-like behaviour in
mice could be reversed by treatment with drugs that stimulate P2RX7.
P2RX7 also plays an important role in the brain's response to
inflammation, which is known to be part of many neuropsychiatric
disorders. Additionally, stress hormones decrease the activity of this
gene, suggesting a mechanism for the onset of depression following
severe stress.
"A person may have the mutated gene, but its 'default setting'
means that they may not develop depression. We don't yet know how
P2RX7 works and we still believe that a multitude of genes feed into
the same pathway that may induce depression," said Professor Barden.
The identification of the gene means that anti-depressants in the
future could target the gene directly. With anti-depressants currently
targeting the serotonin system, P2RX7 is bypassed to an extent.
In animal studies, activators of P2RX7 have an immediate
anti-depressant action, giving hope that new anti-depressant
medication, with a new mechanism of action, can be developed.
Analysis of single nucleotide polymorphisms in genes in the chromosome
12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar
affective disorder. Nicholas Barden et al. May 2006. American Journal
of Medical Genetics Part B: Neuropsychiatric Genetics Volume 141B,
Issue 4, 2006. Pages 374-382
----------------------------------------------------
Let's find it.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=summary&list_uids=5027
to,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=5027
[...]
19. P2X7 alleles modulate LPS-stimulated cytokine production, and may
serve as an amplification loop of innate immunity. <sniP>
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=15120006
Damn, are we prone to dePression and psoriasis?
And since this article says animals as well, i've got an explanation
for kitty.
What about us psoriatics and P2RX7?
Could this gene be far off from the P gene(s)?
randall... we can only hoPe!
123matt
I've had two colonic irrigations that went well. I've scheduled another
because my colon has a lot of thick stuff in there. Doing oil packs as
well to help loosen the junk. Hey, came across this in a med website: By
blocking an enzyme in the body called dihydrofolate reductase,
methotrexate interferes with the production of a form of folic acid that
is important for actively growing cells such as those that comprise the
skin, blood, gastrointestinal tissues, and immune system.
Oddly, do you think it possible that mtx is doing something to aggravate
the psor by indirectly effecting our guts? Just a thought. Hope you are
well. Oh, the irrigationist is gonna do an implant of probacteria during
our last session. :)
Talk to ya
randall
123matt wrote:
> Hi Randal,
> I've had two colonic irrigations that went well. I've scheduled another
> because my colon has a lot of thick stuff in there.
How do you know that? Get scoped? I'd speculate that the extra $ your
spending
on these could have bought you the wit kit. Then you could have
done it yourself. :)
>Doing oil packs as
> well to help loosen the junk.
Looks like i need to swing you the opposite direction for sake of
argument,
http://www.quackwatch.org/01QuackeryRelatedTopics/gastro.html
&
http://en.wikipedia.org/wiki/Mucoid_plaque
>Hey, came across this in a med website: By
> blocking an enzyme in the body called dihydrofolate reductase,
> methotrexate interferes with the production of a form of folic acid that
> is important for actively growing cells such as those that comprise the
> skin, blood, gastrointestinal tissues, and immune system.
> Oddly, do you think it possible that mtx is doing something to aggravate
> the psor by indirectly effecting our guts?
I don't know. It seems counterintuitive to me. Then again how many
times have we fallen in to that Ci trap?
> Just a thought. Hope you are
> well.
I'm OK. Even the last bastions of P (knees, ankles and elbows) cleared
recently. Now, i'm taking out supplements left and right.
> Oh, the irrigationist is gonna do an implant of probacteria during
> our last session. :)
And that will be soon?
Can you get the details on this? I'd love to hear how he/she prepares
it.
And what diet are you gonna do then?
randall..
> Talk to ya
randall
SPecial P News.
Today is MIND TRIP day.
Psoriatics have problems with alcohol.
http://en.wikipedia.org/wiki/Ethanol
We usually like it more then the general poPulation.
SEE:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=12720008&query_hl=9&itool=pubmed_docsum
So, while the P plaque patches need occulsion to block O2 to heal.
The inner linnings of the Gi tract become more permeable due to
alcohol (ethanol-C2H6O) and allow endotoxins (LPS) to translocate
from the gut in to the system. :(
It's a simple equation. LPS->TNF->severity of P
If there was a simple drug to slow alcohol consumption it would
go a long way to lowering severity (PASi) in a huge percentage of the
psoriasis population.
What's new out there?
--------------------------------------------------------------------------
http://abclocal.go.com/wabc/story?section=health&id=4365290
A new drug to help alcoholics kick the habit
(New York-WABC, July 14, 2006) - For most of us, a drink of alcohol is
a way to relax or socialize. But for some, drinking can be dangerous,
even deadly. Alcoholism is the third-leading preventable death in this
country. Now, a new drug could help.
A day at the lake is a perfect day for Tom. He's finally able to enjoy
time alone after battling alcoholism for six years. The addiction
destroyed everything that once mattered. "I lost a career because of
that," he says. "It helped break up my marriage."
Tom would drink up to 10 glasses of whisky a day. "It's miserable.
Basically, your life doesn't belong to you anymore. You're consumed
with consuming alcohol." But today, he can focus on other things --
like fishing -- thanks to a new drug called topiramate.
Physician Neuroscientist Bankole Johnson, M.D., DSC, of the UVa Health
System says the drug is one of the first that targets the brain in
alcoholics. "What we are trying to show is that alcohol dependence is
actually a brain disease in the same way other brain diseases are ...
like migraine or epilepsy," he tells Ivanhoe.
Topiramate works by slowing the effects of dopamine, a chemical in the
brain. In a 12-week study, those who took the drug were six-times more
likely to stop drinking than those who took a placebo pill.
"I think this is very exciting," Dr. Johnson says. Another exciting --
but accidental -- finding was the drug also helped smokers reduce their
cravings.
Since the study, Tom has been sober for more than nine months. "It was
like a miracle to me," he says. "I'm getting my life back, and it feels
great."
Patients in the study took the drug once a week for 12 weeks. Doctors
are now starting another, larger trial to study the effects of
topiramate on alcoholics and smokers. They hope those studies will lead
to FDA approval. The most common side effects of topiramate were
drowsiness and fatigue.
_______________________________________________________
http://www.dailymail.co.uk/pages/live/articles/health/healthmain.html?in_article_id=395414&in_page_id=1774
New drug has alcohol effect 'without the hangover'
Scientists are creating drugs that can help drinkers enjoy all the
pleasures of alcohol - with no downsides.
They believe it's possible to develop an alcohol substitute which
selectively blocks the undesirable effects while leaving the good ones
alone.
Alcohol exerts its effects on the brain mainly by latching onto
signalling molecules called GABA-A receptors.
Psychopharmacologist David Nutt said: "We know what alcohol does. Why
not just make better drugs?"
Harm reduction has a decent track record with other dangerous drugs
such as heroin and nicotine so Dr Nutt believes the same can be done
for alcohol, reports New Scientist.
The trick is to make a mixture of molecules that deliver the beneficial
effects - such as relaxation and sociability - without the the
aggression, nausea and loss of co-ordination that can cause drinkers
and their victims so much grief.
Neuropsychopharmacologist Harry June at the University of Maryland in
the US has tested a compound in rats that prevents alcohol making them
clumsy and drowsy.
Dr Nutt, of Bristol University, is has also had promising results
testing blockers that preserve memory after a drinking session.
He is principally interested in coming up with an alcohol substitute
that does not cause chronic damage to he heart, liver and brain - and
believes the key is held in anti-anxiety drugs called benzodiazepines.
Dr June's researchers have found and patented two compounds that seem
to be able to mimic some of the good effects of alcohol - such as
euphoria and relaxation - in rats and baboons.
But it's unlikely people who like to unwind after a day in the office
would want to pop a pill.
Dr Nutt says drinkers could learn to re-educate their palates to
appreciate substitutes too - as long as they provide the same pleasure.
But Dr Richard Olsen and colleagues at California University have even
been developing magical sobering-up pills. The potent antidote to
alcohol has got drunk rats up and running in minutes by dislodging
ethanol from the brain.
It is widely believed ethanol - booze's active ingredient - is a
general inhibitor of brain activity.
The government is taking the idea of safer alcohol seriously by asking
the Academy of Medical Sciences to look into the issue and make
recommendations.
But Ames Sweet, of the US National Council on Alcohol and Drug
Dependence in New York, said: "People are always trying to find a way
to get drunk without the consequences. It's a misguided illusion."
===============================================
Going further with possible drugs to make one feel sPiritual.
http://www.medicalnewstoday.com/medicalnews.php?newsid=47094
Using unusually rigorous scientific conditions and measures, Johns
Hopkins researchers have shown that the active agent in "sacred
mushrooms" can induce mystical/spiritual experiences descriptively
identical to spontaneous ones people have reported for centuries.
The resulting experiences apparently prompt positive changes in
behavior and attitude that last several months, at least.
The agent, a plant alkaloid called psilocybin, mimics the effect of
serotonin on brain receptors-as do some other hallucinogens-but
precisely where in the brain and in what manner are unknown.
An account of the study, accompanied by an editorial and four experts'
commentaries, appears online today in the journal Psychopharmacology.
Cited as "landmark" in the commentary by former National Institute on
Drug Abuse (NIDA) director, Charles Schuster, the research marks a new
systematic approach to studying certain hallucinogenic compounds that,
in the 1950s, showed signs of therapeutic potential or value in
research into the nature of consciousness and sensory perception.
"Human consciousness...is a function of the ebb and flow of neural
impulses in various regions of the brain-the very substrate that drugs
such as psilocybin act upon," Schuster says. "Understanding what
mediates these effects is clearly within the realm of neuroscience and
deserves investigation."
"A vast gap exists between what we know of these drugs-mostly from
descriptive anthropology-and what we believe we can understand using
modern clinical pharmacology techniques," says study leader Roland
Griffiths, Ph.D., a professor with Hopkins' departments of Neuroscience
and Psychiatry and Behavioral Biology. "That gap is large because, as a
reaction to the excesses of the 1960s, human research with
hallucinogens has been basically frozen in time these last forty
years."
All of the study's authors caution about substantial risks of taking
psilocybin under conditions not appropriately supervised. "Even in this
study, where we greatly controlled conditions to minimize adverse
effects, about a third of subjects reported significant fear, with some
also reporting transient feelings of paranoia," says Griffiths. "Under
unmonitored conditions, it's not hard to imagine those emotions
escalating to panic and dangerous behavior."
The researchers' message isn't just that psilocybin can produce
mystical experiences. "I had a healthy skepticism going into this,"
says Griffiths, "and that finding alone was a surprise." But, as
important, he says, "is that, under very defined conditions, with
careful preparation, you can safely and fairly reliably occasion what's
called a primary mystical experience that may lead to positive changes
in a person. It's an early step in what we hope will be a large body of
scientific work that will ultimately help people."
The authors acknowledge the unusual nature of the work, treading, as it
does, a fine line between neuroscience and areas most would consider
outside science's realm. "But establishing the basic science here is
necessary," says Griffiths, "to take advantage of the possible benefits
psilocybin can bring to our understanding of how thought, emotion, and
ultimately behavior are grounded in biology."
Griffiths is quick to emphasize the scientific intent of the study.
"We're just measuring what can be observed," he says; "We're not
entering into 'Does God exist or not exist.' This work can't and won't
go there."
In the study, more than 60 percent of subjects described the effects of
psilocybin in ways that met criteria for a "full mystical experience"
as measured by established psychological scales. One third said the
experience was the single most spiritually significant of their
lifetimes; and more than two-thirds rated it among their five most
meaningful and spiritually significant. Griffiths says subjects liken
it to the importance of the birth of their first child or the death of
a parent.
Two months later, 79 percent of subjects reported moderately or greatly
increased well-being or life satisfaction compared with those given a
placebo at the same test session. A majority said their mood, attitudes
and behaviors had changed for the better. Structured interviews with
family members, friends and co-workers generally confirmed the
subjects' remarks. Results of a year-long followup are being readied
for publication.
Psychological tests and subjects' own reports showed no harm to study
participants, though some admitted extreme anxiety or other unpleasant
effects in the hours following the psilocybin capsule. The drug has not
been observed to be addictive or physically toxic in animal studies or
human populations. "In this regard," says Griffiths, a
psychopharmacologist, "it contrasts with MDMA (ecstasy), amphetamines
or alcohol."
The study isn't the first with psilocybin, the researchers say, though
some of the earlier ones, done elsewhere, had notably less rigorous
design, were less thorough in measuring outcomes or lacked longer-term
follow-up.
In the present work, 36 healthy, well-educated volunteers-most of them
middle-aged-with no family history of psychosis or bipolar disorder
were selected. All had active spiritual practices. "We thought a
familiarity with spiritual practice would give them a framework for
interpreting their experiences and that they'd be less likely to be
confused or troubled by them," Griffiths says. All gave informed
consent to the study approved by Hopkins' institutional review board.
Each of thirty of the subjects attended two separate 8-hour drug
sessions, at two month intervals. On one they received psilocybin, on
another, methylphenidate (Ritalin), the active placebo.
In designing the study, researchers had to overcome or at least,
greatly minimize two hurdles: the risk of adverse side-effects and the
likelihood that the expectations of getting the test drug or the
placebo would influence subjects' perceptions.
To lessen the former, each subject met several times, before drug
sessions began, with a reassuring "monitor," a medical professional
experienced in observing drug study participants. Monitors stayed with
them during the capsule-taking sessions. Actual trials took place in a
room outfitted like a comfortable, slightly upscale living room, with
soft music and indirect, non-laboratory lighting. Heart rate and blood
pressure were measured throughout.
The researchers countered "expectancy" by having both monitors and
subjects "blinded" to what substance would be given. For ethical
reasons, subjects were told about hallucinogens' possible effects,
butalso learned they could, instead, get other substances-weak or
strong-that might change perception or consciousness. Most important, a
third "red herring" group of six subjects had two blinded placebo
sessions, then were told they'd receive psilocybin at a third. This
tactic-questionnaires later verified-kept participants and monitors in
the dark at the first two sessions about each capsule's contents.
Nine established questionnaires and a new, specially createdfollowup
survey were used to rate experiences at appropriate times in the study.
They included those that differentiate effects of psychoactive drugs,
that detect altered states of consciousness, that rate mystical
experiences and assess changes in outlook.
The study, Griffiths adds, has advanced understanding of hallucinogen
abuse.
As for where the work could lead, the team is planning a trial of
patients suffering from advanced cancer-related depression or anxiety,
following up suggestive research several decades ago. They're also
designing studies to test a role for psilocybin in treating drug
dependence.
###
The study was funded by grants from NIDA and the Council on Spiritual
Practices.
Una McCann, M.D., William Richards, Ph.D., of the Johns Hopkins Medical
Institutions and Robert Jesse of the Council on Spiritual Practices,
San Francisco, were co-researchers.
The commentaries on this study that appear in this issue of
Psychopharmacology are available at:
http://www.hopkinsmedicine.org/Press_releases/2006/Griffithspsilocybin.html
and include remarks by:
Hopkins neuroscientist and Professor of Neuroscience, Solomon Snyder,
M.D.
Former NIDA head Charles Schuster, Ph.D., now Distinguished Professor
of Psychiatry and Behavioral Neuroscience at the Wayne State University
School of Medicine
Herbert Kleber, M.D., a professor of psychiatry at Columbia University
and a former deputy director of the White House Office of National Drug
Control Policy (ONDCP)
David Nichols, Ph.D., with the Purdue University School of Pharmacy and
Pharmaceutical Sciences
Harriet de Wit, Ph.D., at the University of Chicago Department of
Psychiatry. DeWit is the editor of Psychopharmacology.
The following Q&A is with Roland Griffiths, the study's lead
researcher.
* Q 1: Why did you undertake this research?
In the 1950s and 1960s, basic science and applied research studies were
taking place with hallucinogens, offering hints that they might be of
value in psychotherapy, addiction treatment, and creativity
enhancement, and suggestions that the hallucinogens can occasion
mystical-type experiences. Laws enacted in response to excesses of the
"psychedelic 1960s" stopped almost all that work, leaving some
promising threads dangling. Despite ongoing illicit and licit use,
remarkably little is known, from the standpoint of modern
psychopharmacology research, about the acute and long-term effects of
the hallucinogens. Our study is among the first to re-open this field.
Since the Hopkins psilocybin work began, researchers at other major
universities, such as UCLA, the University of Arizona, and Harvard,
have begun planning or are carrying out hallucinogen research.
* Q 2: Do you have any sign that the same brain "machinery" affected by
psilocybin is identical to what people experience in spiritual
epiphanies that occur without drugs?
That work hasn't been done yet, though there is good reason to believe
that similar mechanisms are at work during profound religious
experiences, however they might be occasioned (for example, by fasting,
meditation, controlled breathing, sleep deprivation, near death
experiences, infectious disease states, or psychoactive substances such
as psilocybin). The neurology of religious experience, newly termed
neurotheology, is drawing interest as a new frontier of study.
* Q 3: Is this God in a pill? Does it render God or "revelation"
irrelevant?
The scientific method works with what can be observed in the physical
realm, using tools such as atomic particle detectors, medical imaging
devices, people's responses to psychological tests, interviews, and
behavioral observations. We are attempting neither to validate nor to
invalidate the truth of claims that some people have made about
metaphysical realities as a consequence of their psilocybin experiences
(or as a consequence of their meditation, fasting, or prayer
experiences) - that's beyond our purview as scientists. It is within
the purview of science to study the changes in mood, values, view of
self, and behaviors that may follow such experiences.
Of course it would be a profound mistake to confuse the experience of
something for the thing itself. We are not aware of study participants
who felt their psilocybin experience devalued their own religious
traditions; interviews suggested the opposite was more usually the
case.
* Q 4: Are you trying to find a short cut to the spiritual journey that
some people pursue for years?
Our focus in this research was to study the effects of psilocybin using
the methods of modern psychopharmacology. It's true that
"transformative" changes in values, self-perception, and behaviors have
been reported across cultures and eras as a consequence of
mystical-type experience. This bears investigation.
* Q 5: Should religions feel threatened by this work?
I can't see why.
The psychologist Walter Clark, in his 1958 book The Psychology of
Religion, had this to say: "There is no more difficult word to define
than 'religion'...With full recognition that we are on ground where the
experts disagree...we will venture our own definition. It is our
feeling that religion can be most characteristically described as the
inner experience of the individual when he senses a Beyond, especially
as evidenced by the effect of this experience on his behavior when he
actively attempts to harmonize his life with the Beyond."
Many of the volunteers in our study reported, in one way or another, a
direct, personal experience of the "Beyond." Far from being threatened,
the only thing we can imagine being of greater interest to religions is
whether people live more wholesome, compassionate, and equanimous lives
in consequence of such experiences.
* Q 6: Why did you use volunteers who have active spiritual practices?
Didn't that help assure the results you got?
Psilocybin and similar compounds have been reported to sometimes bring
about experiences called spiritual, religious, mystical, visionary,
revelatory, etc. Such experiences may be difficult psychologically and
emotionally. We felt that volunteers who had some engagement with
prayer, meditation, churchgoing, or similar activities would be better
equipped to understand and consolidate any mystical-type experiences
they might have in the study.
* Q 7: Aren't hallucinogens dangerous? How can you give them to human
volunteers?
No mind-affecting drug is absolutely safe. But the risks of the
hallucinogens can be managed in appropriate research settings.
Unlike drugs of abuse such as alcohol and cocaine, the classic
hallucinogens are not known to be physically toxic and they are
virtually non-addictive, so those are not concerns.
The primary effect of psilocybin, in medium to large doses, is strong
alteration of consciousness. It is possible that such experiences can
trigger latent schizophrenia in susceptible individuals. Thus in our
study we disqualified potential volunteers whose personal or family
psychiatric histories indicate that they may be at increased risk of
that disorder.
Our study confirms that some individuals, during some or all of the
hours of the drug's action, may experience paranoia, extreme anxiety,
or other unpleasant psychological effects. It is not difficult to
imagine such stresses leading to dangerous or inappropriate behaviors,
which may constitute the substance's most prominent risk. We managed
that in our study through a short course of psychological preparation
and through careful and interpersonally sensitive monitoring of each
drug session. The monitors were trained to provide reassurance (e.g.,
supportive words or gentle touch to a hand) if needed.
* Q 8: What kind of substance is psilocybin?
Psilocybin is one of a class of compounds whose primary activity is
known to be on 5-HT-2a/c serotonin receptors. Their effects include
changes in perception and cognition. In the pharmacology literature,
this class of drugs is called "hallucinogens, " though they rarely
cause "hallucinations" in the sense of seeing or hearing things that
are not there. Within other academic fields, the term 'entheogen,'
roughly meaning "spirit-facilitating," is coming into prominence for
this class of substances.
* Q 9: Studies at Hopkins have shown the potential for brain damage
from MDMA ( "ecstasy"). How do you know psilocybin doesn't have the
same risk?
Some studies have shown that MDMA can damage certain nerve cells. There
is no experimental or clinical evidence in animals or humans that
psilocybin, even in very high doses, is similarly neurotoxic. Enough
research has been done with psilocybin, starting in the 1950s, that we
can be reasonably confident that it is not physically toxic in doses
humans ordinarily use. This is consistent with the fact that
psilocybin-containing mushrooms have not, in millennia of use, acquired
a reputation of being physically harmful. Traditions that use
psilocybin mushrooms do, however, caution about psychological and
spiritual risks of using them haphazardly.
* Q 10: Isn't your work similar to what Timothy Leary did?
We are conducting rigorous, systematic research with psilocybin under
carefully monitored conditions, a route which Dr. Leary abandoned in
the early 1960s.
* Q 11: Isn't there a risk that a study like this could encourage abuse
of psilocybin or similar substances?
Our report explains the substantial risks that could easily follow from
use without the psychiatric screening, preparation, and monitoring we
provided in this study.
Herbert D. Kleber, M.D., addressed this question in a commentary
published concurrently with our paper. Dr. Kleber is Professor of
Psychiatry at the Columbia University College of Physicians & Surgeons
and the Director of Division on Substance Abuse of the New York State
Psychiatric Institute. He previously served as a deputy director of the
White House Office of National Drug Control Policy (ONDCP).
Dr. Kleber wrote, "The positive findings of the study cannot help but
raise concern in some that it will lead to increased experimenting with
these substances by youth in the kind of uncontrolled and unmonitored
fashion that produced casualties over the past three decades...
"Any study reporting a positive or useful effect of a drug of abuse
raises these same concerns. In this Internet age, however, where youth
are deluged with glowing personal reports in chat rooms and web sites
as well as detailed information about the various agents and how to use
them, it is less likely that a scientific study would move the needle
much.
"Psychedelic drug use has remained in a relatively constant range over
the past three decades as various fads have come and gone and
enthusiastic personal accounts are balanced by negative reports about
casualties.
Discovering how these mystical and altered consciousness states arise
in the brain could have major therapeutic possibilities, e.g.,
treatment of intolerable pain, treatment of refractory depression,
amelioration of the pain and suffering of the terminally ill, to name
but a few, as well as the...needed improvement in treatment of
substance abuse...so that it would be scientifically shortsighted not
to pursue them."
Huston Smith comments
Huston Smith, holder of 12 honorary degrees, is one of the great
authorities on comparative religion. His book The World's Religions has
for forty years been the most widely used textbook on its subject, and
in 1996 he was the focus of a five part Bill Moyers PBS program, "The
Wisdom of Faith with Huston Smith." See hustonsmith.net for more.
Commenting on the Griffiths et al. study, Smith said:
"Mystical experience seems to be as old as humankind, forming the core
of many if not all of the great religious traditions. Some ancient
cultures, such as classical Greece, and some contemporary small-scale
cultures, have made use of psychoactive plants and chemicals to
occasion such experiences. But this is the first scientific
demonstration in 40 years, and the most rigorous ever, that profound
mystical states can be produced safely in the laboratory. The potential
is great."
Smith also issued a caution and suggested that further research on the
topic include social as well as neurological variables: "In the end,
it's altered traits, not altered states, that matter. 'By their fruits
shall ye know them.' It's good to learn that volunteers having even
this limited experience had lasting benefits. But human history
suggests that without a social vessel to hold the wine of revelation,
it tends to dribble away. In most cases, even the most extraordinary
experiences provide lasting benefits to those who undergo them and
people around them only if they become the basis of ongoing work.
That's the next research question, it seems to me: What conditions of
community and practice best help people to hold on to what comes to
them in those moments of revelation, converting it into abiding light
in their own lives?"
==============================================
Herb out of Africa (Ibogaine) to do a life review.
&
http://groups.google.com/groups/search?q=Ibogaine+psoriasis&qt_s=Search
-----------------------------------------------------------------------------
randall... some herbs are magic
randall
Will the chronic diseases ever be figured out?
You may need to register (free) with medscape to read these.
http://www.medscape.com/viewarticle/537747_1
Emerging Infectious Determinants of Chronic Diseases
Posted 07/10/2006
SiobhƔn M. O'Connor; Christopher E. Taylor; James M. Hughes
Evidence now confirms that noncommunicable chronic diseases can stem
from infectious agents. Furthermore, at least 13 of 39 recently
described infectious agents induce chronic syndromes. Identifying the
relationships can affect health across populations, creating
opportunities to reduce the impact of chronic disease by preventing or
treating infection. As the concept is progressively accepted, advances
in laboratory technology and epidemiology facilitate the detection of
noncultivable, novel, and even recognized microbial origins. A spectrum
of diverse pathogens and chronic syndromes emerges, with a range of
pathways from exposure to chronic illness or disability. Complex
systems of changing human behavioral traits superimposed on human,
microbial, and environmental factors often determine risk for exposure
and chronic outcome. Yet the strength of causal evidence varies widely,
and detecting a microbe does not prove causality. Nevertheless,
infectious agents likely determine more cancers, immune-mediated
syndromes, neurodevelopmental disorders, and other chronic conditions
than currently appreciated.
[...]
http://www.medscape.com/viewarticle/537747_2
http://www.medscape.com/viewarticle/537747_3
http://www.medscape.com/viewarticle/537747_4
http://www.medscape.com/viewarticle/537747_5
http://www.medscape.com/viewarticle/537747_6
=================================================================
This next one was first posted by Skeats last year.
This is a toPic near and dear to our stomachs.
http://www.medscape.com/viewarticle/514108
Diet and Psoriasis: Experimental Data and Clinical Evidence
Posted 10/20/2005
M. Wolters
Summary and Introduction
Summary
Psoriasis is considered as a T-cell-mediated inflammatory skin disease
which is characterized by hyperproliferation and poor differentiation
of epidermal keratinocytes. While susceptibility to psoriasis is
inherited, the disease is influenced by environmental factors such as
infections and stress. Diet has been suggested to play a role in the
aetiology and pathogenesis of psoriasis. Fasting periods, low-energy
diets and vegetarian diets improved psoriasis symptoms in some studies,
and diets rich in n-3 polyunsaturated fatty acids from fish oil also
showed beneficial effects. All these diets modify the polyunsaturated
fatty acid metabolism and influence the eicosanoid profile, so that
inflammatory processes are suppressed. Some patients with psoriasis
show an elevated sensitivity to gluten. In patients with IgA and/or IgG
antigliadin antibodies the symptoms have been shown to improve on a
gluten-free diet. The active form of vitamin D, 1,25-dihydroxyvitamin
D3, exhibits antiproliferative and immunoregulatory effects via the
vitamin D receptor, and thus is successfully used in the topical
treatment of psoriasis. In this review, dietary factors which play a
role in psoriasis are assessed and their potential benefit is
evaluated. Furthermore, the risk of drug-nutrient interactions in
psoriasis therapy is discussed.
Introduction
Psoriasis is one of the most common chronic inflammatory skin
disorders, affecting about 2% of the general population. Prevalence
rates in Europe are quoted to be about 1Ā·5%, whereas in the U.S.A. the
prevalence is estimated to be about 4Ā·6%. In contrast, far lower
prevalence rates have been observed in East Africans, American blacks,
Indians (0Ā·7%), and among the Chinese population (0Ā·4%).[1] While the
causes of the disease are unknown, a genetic predisposition associated
with environmental factors is assumed as a plausible aetiological
explanation.[2,3] The significance of the genetic background becomes
evident with a concordance of approximately 60% in monozygotic
twins.[4,5] The disease has a strong association with HLA-C, with about
two-thirds of patients carrying the HLA-Cw*0602 allele compared with
only 10-15% in the general population. Carriers of this allele have a
higher psoriasis risk and the disease becomes manifest at an earlier
age in these patients.[6,7] Psoriasis is considered as a
T-cell-mediated inflammatory skin disease. T-helper (Th) 1 lymphocytes
produce autoreactive interferon (IFN)-Ī³ and induce further cellular
reactions, resulting in marked increases of keratinocyte proliferation,
abnormal patterns of keratinocyte differentiation, concomitant
inflammation, and dermal proliferation of small vessels.[8]
There are distinct clinical phenotypes of the disease, including
chronic plaque lesions (psoriasis vulgaris of type I, early onset and
type II, late onset), guttate psoriasis, psoriatic erythroderma and
drug-induced psoriasis as well as various forms of pustular psoriasis.
At least 10% of patients develop arthritis. Apart from distinction of
psoriasis types, the actual clinical status at the momentary stage of
disease activity is an important factor determining the psoriatic
phenotype.[1,7]
Psoriasis may substantially affect quality of life. Many different
treatments are available which may allow short-term improvement and
long-term control of the disease, but these measures do not lead to
complete clearing of psoriasis.[2,9] The objective of this article is
to assess dietary factors which play a role in psoriasis and to
evaluate the extent of evidence for potential dietetic measures.
Furthermore, the risk of drug-nutrient interactions in psoriasis
therapy will be discussed.
http://www.medscape.com/viewarticle/514108_2
Energy Intake and Food Selection
Studies have shown that symptoms of inflammatory diseases such as
rheumatoid arthritis can be improved by fasting periods or low-energy
diets.[10,11] The prevalence and severity of psoriasis have been
reported to be lower in periods of insecure food supply. Therefore, the
disease may also be improved by low-calorie diets. In mice, calorie
restriction (by 33% of energy intake) for 4 weeks decreased the
epidermal cell proliferation rate by 45%.[12] In a Croatian study in 82
patients with psoriasis vulgaris who received their usual topical
therapy, 42 patients additionally received a low-energy diet whereas
the remaining 40 were supplied with regular hospital food. After 4
weeks patients on the low-energy diet showed significantly decreased
clinical skin disorders in relation to the control group. The authors
concluded that a low-energy diet could be an important adjuvant factor
in the prevention and treatment of moderate nonpustular psoriasis.[13]
In another study, 20 patients with arthritis and various skin diseases
were studied during a 2-week period of modified fast followed by a
3-week period of vegetarian diet. During fasting, some patients with
psoriasis experienced an improvement, which persisted during the
vegetarian diet.[14] The direct cause of these positive effects is not
sufficiently explained, and various mechanisms are discussed. The most
important reason is probably the lack of arachidonic acid (AA) intake,
resulting in lower leukotriene (LT) B4 production (see 'Polyunsaturated
fatty acids' and Fig. 1). During fasting, CD4+ T-cell activation is
reduced and anti-inflammatory cytokines such as interleukin (IL)-4
increase.[15] Another reason may be a reduction of oxidative stress due
to calorie restriction, because psoriasis appears to be associated with
oxidative stress (see 'Oxidative stress and antioxidants').[16,17] A
vegetarian diet may be beneficial because it is associated with a
reduced AA intake. As psoriasis is positively connected with body mass
index (BMI),[18,19] weight reduction is recommended for obese patients.
Short-term fasting periods may improve severe symptoms and thus can be
suggested for patients with a BMI in the upper range. There have been
several observations indicating that alcohol consumption is highly
prevalent in patients with psoriasis.[20,21] As alcohol stimulates the
release of histamine, skin lesions can aggravate as a consequence.[22]
Moreover, a high alcohol intake may be accompanied by an excessive
intake of high-fat foods and saturated fats and a low intake of
vegetables and fresh fruit.[19,23] Therefore, alcohol intake should be
restricted in psoriasis.
http://images.medscape.com/images/514/108/art-bjd514108.fig1.gif
Polyunsaturated Fatty Acids
Two families of polyunsaturated fatty acids are distinguished depending
on the location of the first double bond counted from the methyl end.
The essential fatty acid linoleic acid (C18:2n-6) belongs to the n-6
family. It is found in seeds, e.g. sunflower seeds, and can be
converted to the more unsaturated derivative, AA (C20:4n-6). Food
sources of AA are only animal-derived foods such as meat and egg yolk.
The fatty acids Ī±-linolenic acid (C18:3n-3), eicosapentaenoic acid
(EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) are the most
abundant n-3 fatty acids in food. Ī±-Linolenic acid is found in linseed
and walnut oil, whereas EPA and DHA are typical fish oil fatty acids,
which are contained in oily fishes such as mackerel and herring. In
addition to their roles in membrane phospholipids, polyunsaturated
fatty acids are required for the formation of eicosanoids which are
metabolic regulators, for example in immune, cardiovascular and
regulatory systems.[24] Eicosanoid members include prostaglandins
(PGs), thromboxanes, LTs, hydroxyl acids and lipoxins. For example, AA
can be converted to PGE2 and to LTB4, whereas eicosanoids derived from
EPA are PGE3 and LTB5 (Fig. 1). The EPA-derived eicosanoids, PGE3 and
LTB5, possess less inflammatory action than do PGE2 or LTB4, both
formed from AA.[24] This is why eicosanoids derived from AA can
exacerbate inflammatory processes and those derived from EPA exhibit
anti-inflammatory properties.[25]
Animal studies indicate that fatty acids can modulate proinflammatory
cytokine production and actions. N-6 polyunsaturated fatty acids such
as AA may enhance IL-1 production and tissue responsiveness to
cytokines, whereas n-3 polyunsaturated fatty acids such as EPA or DHA
have the opposite effect. Among the underlying cellular mechanisms, the
modification of the composition of membrane phospholipids by the
different fatty acids predominates, resulting in changes of membrane
fluidity, altering binding of cytokines to receptors and G protein
activity. Several trials have demonstrated the anti-inflammatory
effects in psoriasis of fish oils which are rich in n-3 polyunsaturated
fatty acids.[26]
Overproduction of AA-derived eicosanoids has been implicated in many
inflammatory and autoimmune disorders and also in psoriatic skin
lesions. Elevated concentrations of AA and LTB4 have been measured in
the skin and erythrocyte membrane of patients with psoriasis.[27,28]
Diets rich in n-3 fatty acids result in the substitution of AA by n-3
polyunsaturated fatty acids in membrane phospholipids. As EPA can act
as a competitive inhibitor of AA conversion to PGE2 and LTB4, diets
rich in EPA exhibit anti-inflammatory effects.[29,30] Low dietary AA
intake which is typical for vegetarian diets can also reduce LTB4
synthesis and may additionally improve inflammation. Although these
mechanisms are well known, results of studies evaluating the effect of
n-3 polyunsaturated fatty acids in the treatment of psoriasis are
inconsistent and many of them were criticized because of shortcomings
of study design.[31]
Several uncontrolled studies with fish or fish oil supplementation have
been carried out. Most of them indicated a positive effect of n-3 fatty
acids which may partly be due to the fact that the patients knew they
were expected to have an improvement from the treatment. In one trial
patients with psoriasis were advised to eat 170 g of white fish daily
for a 4-week run-in period before being randomized either to continue
with the white fish diet or to replace it by 170 g of oily fish daily
for 6 weeks in a crossover design. Modest significant clinical
improvement was observed after the oily fish diet only, whereas the
white fish diet had no effect. At the same time, plasma EPA
concentrations rose in the oily fish group. The authors concluded that
the daily intake of oily fish such as mackerel, sardine, salmon,
pilchard, kipper or herring, which are rich in n-3 fatty acids, might
be a useful adjunct in the treatment of psoriasis.[32]
Four uncontrolled studies with EPA/DHA or fish oil supplementation with
daily dosages between 2 and 12 g n-3 fatty acids reported beneficial
effects of the intervention on psoriasis severity.[28,33-35] A positive
effect of a combination of n-6 and n-3 fatty acids was observed in 17
patients with psoriasis after 4 months in another noncontrolled
study.[36] In an open study testing the effects of fish oil
supplementation in 26 patients with psoriasis, no clinically
significant improvement could be shown in any of the patients with
plaque-type psoriasis vulgaris. Only one patient with generalized
pustular psoriasis showed marked improvement with the fish oil
supplementation, accompanied by decreased LTB4 levels.[37]
Results from randomized controlled trials are less positive. Among four
studies, a benefit of oral n-3 fatty acid supplementation was reported
in one study only,[38] whereas no beneficial effects compared with
placebo were observed in the other three studies.[39-41] The positive
result was described in a randomized placebo-controlled trial with
patients with psoriasis receiving 3 g of oral n-3 fatty acid
(predominantly EPA) from fish oil (10 g) daily. Within this treatment
group a significant lessening of itching, erythema and scaling was
observed after 8 weeks, with a trend towards an overall decrease in
body surface area affected, whereas no change occurred in the olive oil
(placebo) group.[38] In two randomized double-blind controlled studies,
fish oil supplementation of 1Ā·8 g EPA for 8 weeks[39] or 10 capsules
of fish oil three times a day for 3 weeks[37] showed no benefit
compared with olive oil supplementation. No benefit of fish oil
supplementation compared with corn oil, which contains mainly n-6 fatty
acids, was seen in a 4-month, double-blind, randomized multicentre
trial. One hundred and forty-five patients with moderate-to-severe
psoriasis received either 5 g of EPA and DHA or an isoenergetic amount
of corn oil in their diet. Although the ratio of AA and EPA in serum
phospholipids decreased significantly in the fish oil group, the
Psoriasis Area and Severity Index (PASI) score did not change
significantly in either group. Scaling was reduced compared to baseline
in both groups, but only a selected area of skin in the corn oil group
showed a significant reduction in clinical signs. There was no
significant difference in clinical manifestations between the groups.
Clinical improvement was not correlated with an increase of n-3 fatty
acid concentration in serum phospholipids among the patients in the
fish oil group, whereas there was a significant correlation between
clinical improvement and an increase in EPA and total n-3 fatty acids
in the corn oil group.[41] The positive effect of corn oil rich in
linoleic acid may be explained by the fact that LTB4 production is
suppressed at high intakes of linoleic acid.[26]
No effect on chronic stable plaque psoriasis was observed in a
double-blind trial after the supplementation of a combination of n-3
fatty acid-rich marine oil with n-6 fatty acid-rich evening primrose
oil in 37 patients with psoriasis.[42]
In contrast to the mostly negative results from oral supplementation
studies with n-3 fatty acids, promising advances were made in
parenteral application of n-3 fatty acids, indicating positive effects
on acute inflammatory disorders.[43] In a 10-day trial, 20 patients
hospitalized for acute guttate psoriasis with a minimum of 10% of body
surface area involvement were randomly assigned to receive daily
infusions with either a n-3 fatty acid-based lipid emulsion (EPA + DHA
4Ā·2 g daily) or a conventional n-6 lipid emulsion (EPA + DHA < 0Ā·1 g
daily). The severity of disease, which was evaluated by daily scoring
of erythema, infiltration and desquamation and by a subjective scoring
of clinical manifestations, decreased markedly in all patients of the
n-3 group, with significant improvements in all score systems ranging
between 45% and 76% within 10 days. Only moderate improvement was
observed in the n-6 group (16-25% score changes from baseline).
Neutrophil EPA-derived 5-lipoxygenase product formation increased
10-fold in the n-3 group but not in the n-6 group.[44] The benefit of
infusions with n-3 fatty acids (4Ā·2 g of both EPA and DHA) has been
confirmed in a double-blind, randomized, multicentre study with 83
patients hospitalized for chronic plaque-type psoriasis. After 14 days
of intervention the total PASI score decreased significantly in both
groups, the n-3 and the n-6 fatty acid control group, by 42% and 31%,
respectively. A decrease in total PASI of at least 50% between the
admission and the last value was stated in 37% of the patients
receiving the n-3 emulsion and in 23% of the patients receiving n-6
fatty acid-based conventional emulsion. As an increase in neutrophil
LTB5 and platelet thromboxane B3 generation occurred, the observed
effects were probably related to changes in inflammatory eicosanoid
generation.[45] The rapid effect of n-3 fatty acid supplementation in
these studies indicates that intravenous supplementation may be more
beneficial on inflammatory skin lesions than oral supplementation. In a
Cochrane review on base treatment of acute guttate psoriasis, the
authors concluded that there is currently no firm evidence for
intravenous n-3 fatty acids as a base treatment for acute guttate
psoriasis.[46]
Some of the presented study results indicate modest improvements by
additional n-6 fatty acids in psoriasis. Soyland et al.[41] found a
moderate positive effect in the corn oil group and Mayer et al.[43]
observed a moderate improvement after parenteral n-6 lipid emulsion.
Kragballe,[36] who supplemented 17 patients with a combination of n-6
and n-3 fatty acids, found a positive but not significant effect.
Modest improvements may result from a combined fatty acid therapy
because patients with psoriasis have been shown to exhibit low
concentrations of polyunsaturated fatty acids in membrane
phospholipids. Patients with psoriatic arthritis exhibited a
significant increase in saturated fatty acids and a significant
decrease in n-6 polyunsaturated fatty acids in red blood cells compared
with controls.[47] Furthermore, as already discussed, high doses of
linoleic acid suppress LTB4 production.[26]
Gluten
In coeliac disease (CD), the ingestion of gluten-containing cereals
results in small bowel mucosal inflammation and villous atrophy with
crypt hyperplasia. The resulting malabsorption syndrome occurs in
sensitive individuals upon the consumption of wheat, rye, barley,
triticale, oats, spelt and kamut. The symptoms such as diarrhoea and
abdominal distension normalize after the institution of a gluten-free
diet. The toxic compounds are prolamins: gliadin in wheat gluten,
secalins in rye, and hordeins in barley.[48,49] It is assumed that
gluten-sensitive enteropathy commonly manifests with minimal or no
gastrointestinal symptoms and that there is an association between
latent gluten sensitivity and psoriasis.[50-53] In the case of 'silent'
CD, antibody testing can be used to identify gluten-sensitive patients.
Plasma cells produce IgA and IgG against various antigens including
gliadin, transglutaminase, endomysin and reticulin. In diagnosing CD,
IgG and IgA antigliadin antibodies (AGA) and serum antibodies against
tissue transglutaminase have been shown to be useful.[51] Tissue
transglutaminase seems to be the predominant autoantigen in both the
intestine and the skin of patients with CD.[54] Some findings indicate
an elevated incidence of psoriasis in patients with CD, but the data
are inconsistent.[54-56] A case report of a patient with CD and
psoriasis whose skin lesions improved shortly after starting a
gluten-free diet seems to confirm the suggested association between CD
and psoriasis.[57] On the other hand, a gluten-free diet may improve
psoriasis severity even in patients with no CD but with IgA and/or IgG
AGA.[58] AGA are more common in patients with psoriasis than in healthy
persons. Measurement of IgA and IgG AGA by a microenzyme-linked
immunosorbent assay method in 302 patients with psoriasis showed IgA
AGA serum levels above the 90th percentile value of the reference group
in 16% of the patients. Although the mean level of IgG AGA was not
increased in the psoriasis group, there was a correlation between the
values for IgA AGA and IgG AGA.[50] Moreover, the presence of serum IgA
AGA is often associated with duodenal inflammation.[59] Michaelsson et
al.[58] evaluated the effect of a 3-month gluten-free diet in 33
AGA-positive and six AGA-negative patients with psoriasis. They used
the PASI for assessment of disease severity. Thirty patients with AGA
completed the gluten-free diet period and showed a highly significant
decrease in mean PASI. No improvement was found in the AGA-negative
patients. AGA values were reduced after the gluten-free diet in 82% of
those patients who improved. After the gluten-free diet, patients
consumed their ordinary diet for 3 months. During this period, the
psoriasis deteriorated in 18 of the 30 patients with AGA who had
completed the gluten-free period. As CD or latent gluten sensitivity
was diagnosed in only 19 patients it can be concluded that patients
with psoriasis with raised AGA may improve on a gluten-free diet even
if small intestinal histology seems to be normal. The study has been
criticized for some shortcomings of the design such as the small
control group, no randomization and the possibility that the placebo
effect might have played an important role in the positive results.[56]
Should the findings of the study be true, patients with latent gluten
sensitivity exhibited increased bowel permeability despite normal small
intestinal histology. The increased intestinal permeability may allow
the passage of small numbers of microbes which can act as superantigens
and may induce the appearance or exacerbation of psoriasis in
predisposed subjects which could be reversed by a gluten-free diet.
Another explanation of the coincidence of CD and psoriasis may be the
profile of released cytokines. In psoriasis the predominating Th1 cells
mainly produce IFN-Ā® and IL-2 (Fig. 2). T cells from patients with CD
release a similar cytokine profile in response to a gluten challenge in
vitro. Some case reports indicate that elevated serum levels of these
cytokines may be sufficient to result in CD or psoriasis in predisposed
individuals.[56]
http://images.medscape.com/images/514/108/art-bjd514108.fig2.gif
Investigating the proliferating (Ki67) cells and tissue
transglutaminase in involved skin of 28 AGA-positive patients with
psoriasis before and after 3 months of a gluten-free diet showed a
significant decrease in proliferating cells after the diet even in
patients without increased intraepithelial lymphocytes. After the
gluten-free diet, tissue transglutaminase, which was highly
overexpressed in the papillary endothelium of involved skin, decreased
by 50%.[60]
Oxidative Stress and Antioxidants
Oxidative stress and increased free radical generation have been linked
to skin inflammation in psoriasis. Superoxide anion liberation was
elevated in psoriatic dermal fibroblasts, which have been suggested to
play a central role in the inflammatory mechanism of psoriasis.[16]
Patients with psoriasis exhibit several markers of oxidative stress and
show impaired antioxidant status: increased concentrations of
malondialdehyde (MDA), a marker of lipid peroxidation, were measured in
plasma and red blood cells, and decreased plasma levels of Ī²-carotene
and Ī±-tocopherol as well as decreased serum concentrations of selenium
were found.[16,47,61] Results on the activity of antioxidant enzymes
are inconsistent. In one study glutathione peroxidase activity was
stimulated in both erythrocytes and platelets when compared with normal
cells. At the same time the plasma selenium concentration was
significantly reduced compared with the control group.[27] In another
trial, activities of antioxidant enzymes such as catalase and
glutathione peroxidase were reduced.[16] An increased production of MDA
was consistently observed in psoriasis indicating advanced phospholipid
peroxidation of the red blood cell membrane caused by a decrease of
antioxidant resistance. This may explain the decreased membrane
fluidity associated with the exacerbation of the disease.[16] Fish oil
supplementation not only altered the lipid pattern of erythrocyte
membranes but also led to a reduction of MDA in patients with psoriasis
and therefore may reduce oxidative stress.[27] In an Italian
case-control study with 316 patients with psoriasis and 366 controls,
dietary intake was assessed by a semiquantitative food frequency
questionnaire and data were adjusted for age, sex and BMI. Psoriasis
risk (odds ratio) was significantly inversely related to the intake of
carrots, tomatoes and fresh fruit as well as to the Ī²-carotene intake.
The intake of green vegetables showed an inverse association, with
borderline statistical significance. The consumption of vegetables and
fruits may be beneficial in psoriasis due to their high content of
various antioxidants such as carotenoids, flavonoids and vitamin C.[19]
A sufficient status of antioxidants (e.g. vitamin C, vitamin E,
Ī²-carotene and selenium) may be helpful to prevent an imbalance of
oxidative stress and antioxidant defence in psoriasis. While ascorbic
acid acts as a water-soluble antioxidant,[62]Ī±-tocopherol is a
chain-breaking antioxidant that prevents the propagation of lipid
peroxidation.[63]Ī²-Carotene displays antioxidant activity by
scavenging free radicals and is a potent quencher of singlet
oxygen.[64] Selenium is essential for the function of a number of
selenoproteins such as glutathione peroxidases and thioredoxin
reductase which take part in the antioxidant defence.[65] To date, only
a few studies have investigated the effect of antioxidant
supplementation on psoriasis symptoms. In one supplementation trial,
seven patients with psoriasis received selenium 400 Āµg daily for 6
weeks as selenomethionine-enriched yeast.[66] Blood and serum selenium
levels were normal at baseline. After supplementation there was a
slight but significant increase only in the number of CD4+ T cells in
the reticular dermis of the psoriatic lesions. Selenium supplementation
had no marked effect on the clinical condition of the patients.[66] A
previous study also showed no effect of daily supplementation of 600
Āµg selenium-enriched yeast alone or together with 600 IU of vitamin E
on the clinical symptoms of 69 patients with psoriasis. In this
placebo-controlled study, blood, plasma and platelet selenium
concentrations as well as platelet glutathione peroxidase activity and
plasma vitamin E markedly increased in the supplemented group. However,
the mean skin selenium concentration and red cell glutathione
peroxidase activity remained unchanged.[67]
Vitamin D3 and Analogues
Vitamin D is a prohormone which can be produced from
7-dehydrocholesterol by moderate exposure of skin to solar ultraviolet
(UV) B rays. Its deficiency causes rickets, which arises from
insufficient absorption of dietary calcium. A rich dietary source of
vitamin D is cod liver oil. The biologically active form of vitamin D
is produced by hepatic 25-hydroxylation, followed by 1Ī±-hydroxylation,
primarily in the kidney.[68] Beside its significance in calcium
homeostasis and bone metabolism, the active form of vitamin D,
1,25-dihydroxyvitamin D3[1,25(OH)2D3; calcitriol], exhibits effects via
the vitamin D receptor (VDR) in more than 30 different tissues. One
target tissue for 1,25(OH)2D3 is the skin, as keratinocytes have a VDR.
Human cultured keratinocytes exposed to calcitriol showed marked
inhibition of growth and accelerated maturation. The effects on cell
proliferation and differentiation via the VDR led to the concept of
using 1,25(OH)2D3 in psoriasis.[69] Calcitriol and its analogues exert
antiproliferative and prodifferentiative as well as immunoregulatory
activities. VDR ligands directly influence T-cell activation and
modulate the phenotype and function of antigen-presenting cells and
dendritic cells.[70] Meanwhile, vitamin D analogues including
calcipotriene, 1,24-dihydroxyvitamin D3 and 1,25(OH)2D3 are considered
the first line of treatment for psoriasis.[69,71] They show the same
efficacy as potent topical corticosteroids and are well tolerated even
on a long-term basis.[72]
Insufficient vitamin D status is a widespread problem. Circulating
25-hydroxyvitamin D [25(OH)D] concentration is the best indicator to
define vitamin D status. Observations that subjects with a constantly
high UVB exposure living close to the Equator have mean 25(OH)D serum
levels of 107 nmol L-1 led to the assumption that levels above 100 nmol
L-1 can be regarded as adequate, where no disturbances in vitamin
D-dependent body functions occur.[73] In Europe, prevalence of
insufficient vitamin D status is high, as UVB radiation from sunlight
is negligible from October to April at the latitude of 52Ā°N and from
November to February at 42Ā°N. In contrast, skin synthesis of vitamin D
is possible throughout the year at 32Ā°N or closer to the Equator.[73]
Hypovitaminosis D is even more prevalent in older adults because of
limited outdoor activities and decreased capacity of vitamin D
synthesis of the skin compared with younger adults.[74,75] In an
epidemiological survey of 11 European countries, vitamin D deficiency
was found in 36% of elderly male and 47% of elderly female
subjects.[76]
As insufficient vitamin D is a general problem, oral vitamin D
supplementation may be considered in patients with psoriasis who do not
use topical vitamin D analogues. In cases of topical treatment such
supplementation must be avoided because of the risk of hypercalcaemia.
Vitamin B12
Cobalamin (vitamin B12) participates as a coenzyme in two biochemical
reactions in human metabolism. One reaction requiring methylcobalamin
is the remethylation of homocysteine to methionine catalysed by
methionine synthetase (see 'Nutritional status and nutrient-drug
interactions'). Adenosylcobalamin is required as coenzyme for
methylmalonyl-CoA mutase which catalyses the conversion of
methylmalonyl-CoA to succinyl-CoA, a metabolite of the citric acid
cycle. This is an important biochemical reaction in the degradation of
odd-chain fatty acids and of branched-chain amino acids. Cobalamins are
exclusively synthesized by bacteria. Rich sources of cobalamin are
animal organ meats (especially liver and kidney), fish, egg and milk
products.[77]
Vitamin B12 may influence psoriasis due to its role in nucleic acid
synthesis. In vitro studies also demonstrated immunomodulatory effects
of vitamin B12 on T lymphocytes and cytokines.[78,79] There were some
studies in the 1950s reporting therapeutic efficacy after parenteral
administration of vitamin B12 in the treatment of psoriasis. However,
these results could not be confirmed in other studies.[80]
The efficacy of topical vitamin B12 treatment in plaque psoriasis has
been investigated in one study using a vitamin B12 cream containing
avocado oil compared with calcipotriol treatment.[81] There was a more
rapid development of beneficial effects with the use of calcipotriol,
which was shown to be significantly superior to vitamin B12 treatment
after 8 weeks. However, no significant difference between both
therapies was observed after 12 weeks of treatment. Furthermore, there
was better tolerability of the vitamin B12 cream in comparison with
calcipotriol.[81] In this trial it cannot be excluded that components
of the avocado oil such as unsaturated fatty acids may have contributed
to the beneficial effects of the vitamin B12 cream.
Nutritional Status and Nutrient-Drug Interactions
Severe psoriasis has been associated with nutritional deficiencies
because of an accelerated loss of nutrients from the hyperproliferation
and desquamation of the epidermal layer of skin. Furthermore, an
elevated requirement of some nutrients such as antioxidants may occur.
Among 50 hospitalized patients with psoriasis, 18% had decreased total
protein, 16% had decreased serum albumin, 38% had elevated mean
corpuscular volume and 39% had decreased haematocrit. These results
support that patients with widespread psoriasis are at risk to develop
nutritional abnormalities in protein and folate status.[82]
Beside the disease-related risk of poor nutritional status, patients
with chronic diseases are often regular drug users. Therefore they are
at particular risk for drug-nutrient interactions. In psoriasis,
especially systemic therapy can be associated with alterations of the
nutritional status. About 30% of patients with psoriasis have symptoms
that are severe enough to require systemic therapy.[83] On the other
hand, dietary factors can affect a drug's pharmacokinetics and
pharmacodynamics. One systemic treatment in patients with psoriasis is
the folic acid antagonist methotrexate which is used at low doses. It
is hepatotoxic, leads to loss of appetite and its use is
contraindicated in patients with poor nutritional status.[84] Patients
with psoriasis who received low-dose methotrexate therapy (25 mg
weekly) had significantly higher fasting plasma homocysteine and lower
plasma folate levels than age-matched controls.[85] This finding is
supported by studies in patients with rheumatoid arthritis on
methotrexate therapy.[86,87] Homocysteine is derived from methionine
and is used as a sensitive marker of folate status. Elevated
homocysteine concentrations are associated with an elevated risk of
atherosclerosis and may increase the risk of dementia.[88-90]
Homocysteine can be degraded through two enzymatic pathways: the
remethylation of homocysteine to methionine is catalysed by the
methionine synthetase. In this reaction 5-methyl tetrahydrofolic acid
is involved as a methyl group donor, while vitamin B12 is the
intermediate acceptor of the methyl group. In folate deficiency, plasma
homocysteine rises. In the trans-sulphuration pathway, homocysteine
forms cysteine, but this degradation pathway is not sufficient to
normalize homocysteine concentrations in folate deficiency.
Homocysteine can be used as a sensitive marker of folate status in
patients with psoriasis receiving methotrexate. Folic acid supplements
should be prescribed routinely to these patients. In order to reduce
side-effects, 5 mg of folic acid two to five times weekly is commonly
given to patients receiving methotrexate.[91]
Another systemic therapy in psoriasis is ciclosporin, an
immunosuppressive agent. Owing to downregulation of the cytochrome P450
3A4 enzyme in the intestinal wall, the oral bioavailability of
ciclosporin increases by more than 60% when taken with grapefruit
juice. Patients should be advised to avoid the consumption of
grapefruit juice when taking ciclosporin.[92-94]
Retinoids such as etretinate are synthetic analogues of retinoic acid
(vitamin A). Systemic retinoids can induce symptoms of hypervitaminosis
A including headache, weakness and anorexia. Patients taking retinoids
should be advised to avoid food sources rich in vitamin A, particularly
liver. Retinoids can also induce hyperlipidaemia. Thus regular
monitoring of this side-effect is necessary. Serum triglycerides can be
significantly lowered by a diet low in saturated fatty acids and high
in n-3 fatty acids from fish such as mackerel, sardine, salmon, herring
or fish oil supplements.[95] Furthermore, alcohol intake and dietary
monosaccharides should be reduced.[96,97]
Among the pro-oxidant 9-anthrones that are used in topical treatment of
psoriasis, dithranol is the most common therapeutic agent. The
therapeutic effect is based on the generation of reactive oxygen
intermediates and anthrone radicals produced in the skin. As superoxide
dismutase and Ī±-tocopherol acetate were effective in inhibiting
cytokine elevation induced by dithranol, systemic antioxidant
administration may reduce dithranol-associated side-effects.[16]
Conclusions
The diet is one factor in the aetiology and pathogenesis of psoriasis.
Vegetarian diets may be beneficial for all patients with psoriasis due
to the low AA intake and the resulting reduced formation of
inflammatory eicosanoids. Although the results of oral fish oil
supplementation are inconsistent, patients can be recommended to
include fish rich in n-3 polyunsaturated fatty acids in their diet.
Moreover, in patients hospitalized for acute psoriasis parenteral n-3
polyunsaturated fatty acid infusions may be beneficial. Further
investigations are needed to clarify the role of a gluten-free diet and
underlying mechanisms on psoriasis in gluten sensitivity. A gluten-free
diet may improve psoriasis severity in patients with IgA and/or IgG
AGA. To date, apart from measurement of AGA or tissue transglutaminase,
patients may be recommended to try whether a withdrawal of gluten for
at least 3 months reduces the symptoms. Owing to its role in
proliferation and maturation of keratinocytes, vitamin D has become an
important therapeutic option in the treatment of psoriasis. As
hypovitaminosis D is widespread, patients who do not use topical
vitamin D analogues may benefit from vitamin D supplements. More
well-designed trials are needed to confirm or reject the benefit of
dietary manipulation in psoriasis. Drug-food interactions have to be
considered in patients with psoriasis.
Author:: Maike Wolters. E-mail: maike.wolters @lw.uni-hannover.de
References:: http://www.medscape.com/viewarticle/514108_References
-------------------------------------------------------------
randall..
123matt
Thanks for this latest round. WOW! You've really got me thinking about
this colon cleansing. Coincidentally, my sister just yesterday had the
colonscopy procedure done and urged me to do so as well. I don't want to
cancel the next colon clease because she's going to do the implantation of
probacteria. Then I'll continue to take the proflora stuff in liquid form.
Now, my question for you is: do you think it's all bunk? I mean, the
wholewhey route is really the same thing: cleaning the gut and implanting
probacteria. What's the difference? Hmmm..I do believe I'll do the
colonscopy since my sister (a nurse) advises it due to our family history
and polyps. Ah, more research is needed, I see. But onwards...we're
getting closer to a truth with the diet. I'm surrendering the gluten for
two months. I read this: "In patients with IgA and/or IgG antigliadin
antibodies the symptoms have been shown to improve on a
determine my diabetes extent was some sort of antigliadin antibodies"
test--or something like it.
Well, again, thanks for the links and info. As always, food for thought
:)
Take care
Matt
randall
> Hey Randall,
> Thanks for this latest round. WOW! You've really got me thinking about
> this colon cleansing. Coincidentally, my sister just yesterday had the
> colonscopy procedure done and urged me to do so as well. I don't want to
> cancel the next colon clease because she's going to do the implantation of
> probacteria.
For health in general or does she have P?
>Then I'll continue to take the proflora stuff in liquid form.
> Now, my question for you is: do you think it's all bunk?
No. But for the longest time, I followed Robert Gray (The Colon Health
Handbook- New Health Through Colon Rejuvenation) ), Bernard Jensen
(Tissue Cleansing Through Bowel Management) and David Ehrlich
(The Bowel Book) with disappointing results. I did more whacked
out sh*t to get good flora in the colon again it wasn't funny.
After the wit kit implant and one month of the required bland diet,
I knew that the secret to all of this was mine.
My P levels sunk to near zero and I felt great. That biota (flora
colony) of not us
is the key to us. Yet, you still have free will. You can be haPPy or
craPPy.
I've chosen to test the colon to find the pathways that will lead
to a cure beyond lifestyle and within reason of course. Being a
hedonistic
alcoholic certainly supports the wrong flora. LOL
For sins of that ilk we do wear them on the skin. <g>
> I mean, the
> wholewhey route is really the same thing: cleaning the gut and implanting
> probacteria.
If you do the wit kit implant and diet whether the colon is *cleaned*
up or not,
it sets a demarcation point.
http://en.wikipedia.org/wiki/Demarcation_problem
Your system certainly responds to the nascent colony of new biota
and cleans away as the psoriasis fades from view. One knows
that the new flora is establishing based on bowel performance.
But, by not sticking to the diet you hamper the results.
> What's the difference? Hmmm..I do believe I'll do the
> colonscopy since my sister (a nurse) advises it due to our family history
> and polyps.
If you have them, they can clip them. Watch the scope screen,
you won't see the so called impactions, that is the bunk pushed
by the confused alts. Either they don't know or their working a scam.
Judging what I see, they don't know the truth or they would
be all using the wit kit. Then they would be allowed to pontificate
on diet, till their newly born healthy reimplanted adherrents are
running wild again. lol
> Ah, more research is needed, I see. But onwards...we're
> getting closer to a truth with the diet. I'm surrendering the gluten for
> two months. I read this: "In patients with IgA and/or IgG antigliadin
> antibodies the symptoms have been shown to improve on a
> gluten-free diet."
It's my feeling at this point that the gluten won't be as big
a problem afterwards. I wasn't as aware of it when I did it,
but it seems like I could eat more wheat with less severe
reactions post wit kit implant.
I was all prepared to go with rice starch as a substitute and
it wasn't needed. It could be in my mind, but if it wasn't
I knew I could work around it.
Taking the wheat out wasn't as big a problem as going vegetarian
again. My prior meatless diets lead to me looking like something
from a prison camp. I thought i looked good with less p, but the
rest of those around me only saw a skinny bean pole with
a big grin. They never really noticed the p anyway.
It was odd and when I had gotten pissed at the P, i would
starve it back in to submission. It was so simple, that i needed to
nail the gut connection back then and get off the roller coaster.
> Could be true.
Do what you do. I did and here I am.
I was taken in by nearly every good scam out there. Most of those
folks really believed in what they had. They bought the lie lock stock
and barrel.
When It didn't help me, it was my fault as their world view was in
jeopardy.
All that crap didn't waver my resolve. I was the character in
groundhog's day. I had all the time in the world and one
day things would change and they did.
randall
123matt
Yeah, my sister had the colonoscopy because my dad had polyps when he was
about our age. But my sister gets it done "on the house" (husband is ex
military) and I just found out the procedure is a whopping thousand
bucks--so it's gonna wait. So the secret of your success is the
implantation and diet, the first of which i'll have thursday of this week.
Then it's the rough diet for a month. Question: do you think consumption of
turkey would be cheating terribly?
Question: is there a particular type of proflora in the Witkit? I'd like
to compare it with what the lady 'doc' is pumping into me. I think I'll
get generous doses of lactobacillus acidophilius, bifidobacterium bifidum,
lactobacillus rhamnosus, lactobacilluis salivarus, and all that lot. Is it
pretty much the same as you had? What I'm getting at is this: is there
something 'unique' in the witkit that isn't in the other probiotic
formulas?
Okay, wish me luck that the armies of probis attack the bad guys. Talk
at ya soon,
Matt
randall
123matt wrote:
> Hey, glad to hear that wheat may not need to be totally out of my diet!
> Yeah, my sister had the colonoscopy because my dad had polyps when he was
> about our age. But my sister gets it done "on the house" (husband is ex
> military) and I just found out the procedure is a whopping thousand
> bucks--so it's gonna wait.
Ah, does your sister have psoriasis? And your dad, now that
you mention your genetic proclivity?
> So the secret of your success is the
> implantation and diet, the first of which i'll have thursday of this week.
> Then it's the rough diet for a month. Question: do you think consumption of
> turkey would be cheating terribly?
NO meat. Period. You need to buy the wit kit to get the most bang
for your buck. The wit kit instructions keep you on track.
> Question: is there a particular type of proflora in the Witkit?
http://www.thewholewhey.com/Item5.htm
&
http://www.kyolic.com/html/products/probiotics/kyodophiluscaps.htm
Look for info on this second site. They are the producer after all.
> I'd like
> to compare it with what the lady 'doc' is pumping into me. I think I'll
> get generous doses of lactobacillus acidophilius, bifidobacterium bifidum,
> lactobacillus rhamnosus, lactobacilluis salivarus, and all that lot. Is it
> pretty much the same as you had? What I'm getting at is this: is there
> something 'unique' in the witkit that isn't in the other probiotic
> formulas?
It's more a function of the process. The diet is critical once you've
been
implanted.
Imagine a baby for sake of illustration. They don't have teeth to eat
those
foods that they don't really need anyway, provided their being
breastfed.
This goes hand in hand with the flora in the Gi tract and it's ability
to
rule the terrain and be able to bounce back from sickness and
adversity,
like a course of antibiotics for instance.
Furthermore, if you've changed diapers during the change to meats,
the odor is a tell tale sign. If you get my drift.
Current research in biofilms could help to reestablish viable
flora colonies in the near term,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20biofilm*+gut
So think of this as seeding a plot of ground that you've prepared and
are
willing to grow the best biota you can and that entails avoiding all
those
things that will screw up the process.
> Okay, wish me luck that the armies of probis attack the bad guys. Talk
> at ya soon,
> Matt
If your doing this soon, contact me offlist for help.
randall
123matt
I'll duplicate this to the aol address. I think that is what you meant by
'offlist'. Seems the Witkit's axis of good guy flora is the same as what I
have now: Floramed. On the box it says: ...patent pending bio tract
delivery technology..capable of delivering 80% or more of the caplet's dry
weight through stomach acids. Protective gel layer surrounds the caplet and
isolates the bacteria...etc.
I also bought these plant enzymes to help with digestion. Thought it
worth a try. Anyway, I've spent enough so will forego the Witkit since I'm
already getting the implantation done thurs and have a supply of these
Floramed capsules. I'll stick to the meat-free diet, though! Ouch, it'll
be difficult as I'm getting back into the weight lifting. More eggs, huh?
Gotta watch them, as well. If only some genius would come up with a
proflora candy filled with protein!
Oh, sis doesn't have P, but dad did/does. I've got the modification:
pityriasis (though years back did have full P). Let's see.
Talk to ya--and thanks for the info. I'm learning. :)
Matt
randall
123matt wrote:
> Hi Randall,
> Seems the Witkit's axis of good guy flora is the same as what I
> have now: Floramed. On the box it says: ...patent pending bio tract
> delivery technology..capable of delivering 80% or more of the caplet's dry
> weight through stomach acids. Protective gel layer surrounds the caplet and
> isolates the bacteria...etc.
http://www.dot-networth.com/Merchant2/merchant.mv?Screen=PROD&Store_Code=BSHS&Product_Code=FloraM
Looks good on paper. I suppose i could print it out. Lets wait for your
results.
> I also bought these plant enzymes to help with digestion. Thought it
> worth a try. Anyway, I've spent enough so will forego the Witkit since I'm
> already getting the implantation done thurs and have a supply of these
> Floramed capsules.
I checked out the zymeMax as well. Under the oilcan?
> I'll stick to the meat-free diet, though! Ouch, it'll
> be difficult as I'm getting back into the weight lifting. More eggs, huh?
> Gotta watch them, as well. If only some genius would come up with a
> proflora candy filled with protein!
After a week or so you don't miss the junky stuff as much as you'd
think.
> Oh, sis doesn't have P, but dad did/does. I've got the modification:
> pityriasis (though years back did have full P). Let's see.
> Talk to ya--and thanks for the info. I'm learning. :)
Oh. I hope it works for your P. Since i've had more then a few
people with other atopic conditions we can only hoPe.
KeeP us posted.
randall
> Matt
randall
Some people are pushing fruit/plant base diets and digestive enzymes as
a way
to p salvation.
Low energy diets with plant foods that avoid n-6 fats (most vegetable
oils) will clear your psoriasis. Taking digestive enzymes at the same
time tricks you in to thinking that they are doing the heavy lifting.
This is what i posted to the npf forum in regards to
taking digestive enzymes.
-------------------------------------------------------------------------
Hi,
Eating a low energy diet does work for psoriasis according to
the post in this thread. (Sorry about blowing the title line.
It's arachidonic acid (AA) not arahidonic. How can I fix that?)
A simple one letter mistake, could be the same with some
gene for psoriasis. Rest assured that a bunch of people
are looking at that. I sent my blood in to the NPF project
with Dr. Bowcock in the 90's and have followed her
work ever since. Good work NPF and all the scientists
following our cause!!
Back to AA. Some of you need the other one as well. lol
Is it due to a lack of arachidonic acid in low energy foods
that a low energy food diet works?
Yes!
So forget about the $$$ draining suPPlements. I've taken enough to be
able to tell you what works and what doesn't.
How important is it to take digestive enzymes?
http://www.quackwatch.org/01QuackeryRelatedTopics/PhonyAds/mp.html
Are you really full of craP?
http://en.wikipedia.org/wiki/Mucoid_plaque
Or is this a riP off?
http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Enzyme_Therapy.asp?sitearea=ETO
If you want to WORRY about a pathogen, i'll find you one.
OK. Here's a brand new one today on pubmed for Psoriasis and PV-B19.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16862431&query_hl=6&itool=pubmed_docsum
A high prevalence of parvovirus B19 DNA in patients with psoriasis.
<sniP>
Department of Dermatology, School of Medicine, Mersin University,
33079, Mersin, Turkey, aycac...@yahoo.com.
Psoriasis is a common inflammatory skin disease. Infectious models are
considered to be of pathophysiological importance in psoriasis. The
immunological profile of stable psoriasis plaques suggests that viral
antigens may be important. Human parvovirus B19 (PVB19) is a
single-stranded DNA virus that causes various clinical symptoms.
Several case reports have suggested associations between PVB19
infection and various chronic autoimmune and dermatologic diseases.
There has so far been no information regarding the role of PVB19 in
psoriasis, except psoriatic arthritis. In this report, to investigate
the role of PVB19 in psoriasis, we analyzed PVB19 DNA of peripheral
blood from psoriatic patients (n = 47) in comparison with blood donors
(n = 20). We also determined the presence of anti-PVB19 IgG and IgM
antibodies by using enzyme-linked immunosorbent assay (ELISA). We found
that the presence of PVB19 DNA in patients with psoriasis (38%) was
significantly higher than in controls (0%, P < 0.01). Anti-PVB19 IgG
antibodies were detected in 79% of the cases while only 6% had
anti-PVB19 IgM antibodies. PVB19 DNA presence was associated with
seropositivity for anti-PVB19 IgG (P < 0.05) but not with IgM
antibodies, indicating subclinical activation of latent infection. No
correlation was found between the presence of PVB19 DNA and a patient's
age, sex, type of psoriasis, or psoriasis area and severity index. The
data demonstrated a statistically significant association between
psoriasis and PVB19. Therefore, we suggest that PVB19 infection may be
of pathophysiological importance in psoriasis.
PMID: 16862431
http://en.wikipedia.org/wiki/Parvovirus_B19
Makes one wonder what's up with this in Turkey psoriatics? Do they kiss
their infected puPPies or what? LOL
Quick, lets send them a CARE package full of digestive enzymes. <w>
Or we can look at the P genes and ask relevant questions regarding
PV-B19?
Gosh the NPF is most likely already on toP of it?
Randalll... this ones to hard to digest!
randall
This is a biggie.
Monster drug? Monster vaccine? Do you need it? Will it helP psoriatics?
http://www.kfmb.com/features/healthcast/story.php?id=58293
Local Scientists Develop Anti-Obesity Vaccine
Last Updated:
07-31-06 at 3:08PM
Losing weight is never easy. More than one billion people on the planet
are overweight, but now local scientists are experimenting with an
anti-obesity vaccine that could help people lose weight without
dieting.
For Americans battling the bulge, losing weight can be a full time
occupation. But what if you could vaccinate yourself against being
overweight?
Scientists at the Scripps Research Institute in La Jolla say it may be
possible, and they've developed a shot that could someday help dieters
shed their unwanted pounds.
"So basically what we've discovered is a vaccine which impacts a
hormone called ghrelin and ghrelin is thought to be involved in both
hunger and storage of fat and metabolism," said Doctor Kim Janda with
the Scripps Research Institute.
When that vaccine was given to lab rats, the animals continued to eat
normally, but gained less weight and had less body fat then the rats
who weren't vaccinated.
"The animals that were vaccinated with the correct type of vaccine ate
the same, drank the same, but their weight gain was slowed by a
dramatic amount compared to the one's that weren't vaccinated
correctly," Doctor Janda continued.
It's not clear how the ghrelin hormone influences weight gain and fat
storage in the body, but the Scripps vaccine uses the body's own immune
system to keep the hormone from reaching the brain. And that helped the
lab rats lose weight without changing their diet or increasing their
level of exercise.
"We though we'd see some type of change in weight gain, but we also
though there would probably be a decrease in feeding and actually we
didn't see that, which was actually quite surprising," Doctor Kim Janda
noted.
The vaccine is still in the early experimental stages and it could be
years - if ever - before it's available to humans. But the researchers
say they are pleased with their initial results and hope the vaccine
could eventually become a powerful weapon in combating obesity.
The Scripps researchers say they haven't detected any side effects
associated with the vaccine, but they plan on conducting more animal
studies to be sure it's safe before testing it on humans.
-----------------------------------------------------------
randall... brave new world? Skinny New World on the horizons.
randall
P News that is sPecial.
OK, I know. Who makes that one uP?
I confess. :)
Let me know if this one isn't!
>From Stanford Uni. Med School....
http://www.sciencedaily.com/releases/2006/08/060802182910.htm
Mapping System Tells Skin Cells Whether To Become Scalp, Palm Tissues
Global-positioning system aficionados know that it's possible to
precisely define any location in the world with just three geographic
coordinates: latitude, longitude and altitude. Now scientists at the
Stanford University School of Medicine have discovered that specialized
skin cells use a similar mapping system to identify where they belong
in the body and how to act once they arrive.
(randall note: Is that why our skin cells are acting like cells in the
gut with crohn's, pumping out TNF-a?)
These cellular cornerstones direct embryonic patterning and wound
healing by sending vital location cues to their neighbors, and may help
in growing tissue for transplant or understanding metastatic cancer.
"There is a logic to the body that we didn't understand before," said
John Rinn, PhD, a postdoctoral scholar in the laboratory of Howard
Chang, MD, PhD, assistant professor of dermatology. "Our skin is
actively maintaining itself throughout our life, and these 'address
codes' help the cells know how to respond appropriately." Rinn is the
first author of the research, which is published in the current issue
of Public Library of Science-Genetics.
Until now it's been a mystery as to how adult skin, which consists of
basically the same components all over the body, knows to grow hair in
some areas like the scalp, while manufacturing sweat glands, calluses
and fingerprint whorls in others. In 1969, well-known developmental
biologist Lewis Wolpert authored a famous treatise that described two
possible ways for cells to know where they are in the body: Either they
infer their location and adjust their behavior based on interactions
with nearby cells, or they deduce their "positional identity" through
the use of some type of coordinate system. The findings from the new
Stanford study bolster the second possibility.
(randall note:: so our outside [skin] is thinking it's inside [lamina
propria] somehow?)
The scientists analyzed the gene-expression profiles of adult
fibroblasts from more than 40 areas of the body. They found about 400
genes whose expression patterns varied with the cells' original
location. Those from the top half of the body - arms, head and chest,
for example - shared expression patterns that were markedly different
from the patterns shared among cells from the bottom part of the body,
such as the legs and feet. Similar patterns existed among cells
originating close to or far from the center of the body, and those from
the outer or the inner layer of the skin.
(randall... alright.. the P genes may be explained due to position)
While these three rough anatomical divisions don't provide the precise
coordinates of a global-positioning system, they do help explain
similarities between the skin on the palms of the hands and the
relatively distant soles of the feet. Like botanically similar areas of
the world that share a latitude and altitude but differ in longitude,
both the palms and soles are on the outer layer of the skin far from
the center of the body and are more like one another than like their
biological neighbors.
(randall note:: Holy craP-a-zoid.... will JXStern have an answer for
psoriasis symmetry)
"Ideally, we can use this finding to develop a positional map that will
allow us to correlate location with function in a way that will make it
easier to regenerate certain parts of the body," said Rinn. "For
example, if we need to grow skin in the laboratory to graft onto
someone with badly burned palms, we'll know how to turn on the specific
genes that make that type of skin." ____The implications are vast._____
Fibroblasts and other skin cells also comprise the lining of the lung
and intestine as well as internal organs.
Not every kind of skin cell expresses gene patterns that can be
correlated with their location in the body; the study found no such
association in endothelial cells, which might depend on signals from
surrounding cells.
(randall note:: so, is LPS in the skin begatting TNF-a? )
"It's not like every cell has this code," said Rinn. "I like to think
of the fibroblasts as wise, old parental cells who may tell the others
how to behave." Their input is invaluable during embryogenesis, normal
growth and wound healing, each of which requires location-specific
responses by cells. Many of the genes identified by Rinn are known to
be important in patterning the early embryo.
Rinn and his colleagues speculate that some of these processes may
require more specific location indicators than the three they've
currently identified. It's possible that additional cues may be
provided by variations in gene expression levels too subtle to be
detected in their current study. Alternatively, cell types other than
fibroblasts or endothelial cells may express signals that further
refine the current rough map. Finally, it's possible that adults simply
don't need the same level of precision mapping as a developing embryo,
and they stop broadcasting the finer points of the signal when it's no
longer necessary.
Rinn and Chang's Stanford colleagues who participated in the research
include research assistant Chanda Bondre; Hayes B. Gladstone, MD,
assistant professor of dermatology; and Patrick Brown, MD, PhD,
professor of biochemistry. The research was funded by the Damon Runyon
Cancer Foundation and the Howard Hughes Medical Institute.
Source: http://med.stanford.edu/
http://mednews.stanford.edu/releases/2006/august/skin-gps.html
---------------------------------------------------------------------------------------------------------------------------------------------------
A good skin story if I've ever heard one. Tracking the actual cells
that pumP out
TNF or IFN etc, should help to resolve so much of what the pathogenesis
is
all about.
Moving on.
As those things (supplements/foods) that are good for you and why
become known.
So be it. If you want to know, I don't blame you.
http://www.vrp.com/art/1181.asp
Glutathione: Life-Extending "Master Antioxidant"
Ward Dean, MD
Glutathione (GSH) is a tripeptide molecule composed of glutamic acid,
cysteine and glycine. It is one of the main nonprotein antioxidants in
the cell, and has been referred to as the body's "master antioxidant."
Glutathione is present in nearly all living cells, and without it they
can't survive. The major functions of glutathione in the body include
protecting cells against the destructive effects of free radicals;
detoxifying external substances such as drugs, environmental pollutants
and carcinogens; maintaining cell membrane stability; regulating
protein and DNA biosynthesis and cell growth; enhancing immunologic
function through its influence on lymphocytes; prostaglandin synthesis;
and amino acid transport.
Clearly, with such widespread functions, glutathione has major effects
on health at the molecular, cellular and organ levels.1,2 Glutathione
and its related enzymes glutathione peroxidase (GPx), and glutathione
reductase (GR), constitute what is known as the "glutathione system"
(Fig. 1).3
Mitochondrial glutathione is critical to the healthy cell, and is
probably the most important antioxidant defense system within the
mitochondria. Age-related alterations in these enzymes can have a
profound adverse effect on health, as this article will explain.
Age-Related Changes in Glutathione
Drs. J.P. Richie and Calvin Lang, of the Department of Biochemistry,
University of Louisville, were the first to propose that a glutathione
deficiency might be a biochemical cause of the aging process. They
demonstrated that glutathione levels decline with age in a number of
organisms, including mosquitoes, mice, and man. They proposed that
restoring glutathione tissue concentrations to those of younger
organisms might result in an extension of the lifespan.
These scientists first tested their hypothesis using adult mosquitoes.
They fed magnesium thiazolidine-4-carboxylic acid (MgTCA) (which is
known to increase glutathione) to the mosquitoes, and measured the
insects? glutathione levels and lifespans. The MgTCA supplementation
increased GSH levels by 50-100 percent, and increased www. lifespans by
30-38 percent over control values (Fig. 2), confirming the GSH
deficiency hypothesis and demonstrating a specific biochemical
mechanism of aging that can be nutritionally modified.4
In a related study, Dr. G. Buonous of the Montreal General Hospital
Research Institute, Quebec, studied the effects of a whey-rich diet on
tissue glutathione concentrations and survival of 21-month-old mice
(equivalent to a human age of about 55-60). The study was performed
over six months, until the mice were the human equivalent of about 80
years old. As in the MgTCA-fed mosquitoes, glutathione tissue
concentrations and longevity of the whey-fed mice increased
significantly above control levels.5
Dr. Lang and his colleagues, as well as a number of other scientists,
found that blood glutathione levels predictably declined with age in
healthy men and women ranging in age from 20 to 94, just as they do in
mosquitoes, mice and rats.1,6
Scientists at the University of Pavia found that glutathione peroxidase
(GSH-Px) levels also follow this age-related pattern up to about age 75
(Fig. 3), after which they noted a slight increase with age in a
cross-sectional study (Fig. 4). They interpreted this as a
self-selection process, which enabled those with the highest
glutathione peroxidase levels to survive the longest.7
In another study of enzyme activity in the very old, Dr. Helle Anderson
and colleagues at Odense University in Denmark compared the levels of
glutathione reductase (GR) in 41 centenarians between 100-105 years
old, to that in 52 community controls between the ages of 60-79. They
found that the mean glutathione reductase (GR) activity was
significantly higher in centenarians than in the group of younger
elderly subjects, and that centenarians with the best functional
capacity tended to have the highest GR activity.
They concluded that high GR activity appears likely to be associated
with increased survival.8 In a later study, Lang?s group evaluated
glutathione levels in 87 women in excellent physical and mental health,
ranging in age from 60 to 103. The scientists found that all subjects
had very high blood glutathione levels. They followed these women for
five years, and concluded that ?high blood glutathione concentrations
? are characteristic of long-lived women.?9
Glutathione in Health and Disease
Just as high glutathione levels are related to increased survival and
longer life in all organisms tested so far, lower levels are related to
poorer health and a number of chronic degenerative diseases, including
heart disease, arthritis, hypertension, diabetes, cancer,
genitourinary, gastrointestinal, and musculoskeletal diseases,
age-related macular degeneration (ARMD), preeclampsia, cataracts,
chronic renal failure, leukemia, respiratory diseases like COPD and
adult respiratory distress syndrome (ARDS), hearing loss, and
AIDS.1,10-14
Lang concluded that decreased GSH is a risk factor for chronic diseases
and may be used to monitor the severity and progress of the diseases.15
Conversely, Dr. Mara Julius of the Department of Epidemiology,
University of Michigan, in a study of 33 subjects over the age of 60,
found that higher glutathione levels were associated with fewer
illnesses and higher levels of self-rated health, lower cholesterol,
lower body mass index and lower blood pressures. The author noted that
this was the first study that showed an association of higher
glutathione levels with higher levels of physical health in a
community-based sample.16
Glutathione and Detoxification
One of glutathione?s primary roles in the body is to detoxify a
number of drugs and toxins. Acetaminophen (APAP, i.e., Tylenol) has
been studied intensively in regard to its glutathione-depleting
properties, and with regard to glutathione?s ability to prevent
APAP-induced liver and kidney damage.
Since GSH levels decrease with aging in all tissues, including the
liver and kidney, older organisms are thus at even greater risk to
APAP-induced liver and renal damage than younger organisms.
Lang's group studied the effect of APAP on the livers of mice of
different ages, and the extent of GSH depletion and recovery. In
control animals, GSH concentrations decreased about 30 percent over the
lifespan of the aging mouse, compared to younger animals.
Four hours after APAP administration, GSH levels of the young, growing
(3- to 6-month-old), mature (12-month-old), and old (31-month-old) mice
decreased about 70 percent. The growing and mature mice recovered to
near control values by 24 hours (94 and 66 percent, respectively). In
contrast, old mice recovered only 41 percent in 24 hours (Fig. 5).
These results clearly demonstrate that the aging mouse liver is not
only deficient in GSH, but has a reduced recovery capacity.17,18 This
illustrates the danger of chronic administration of
glutathione-depleting drugs like Tylenol-especially to older people.
Increasing Tissue Glutathione Levels
It is clear that those with the highest glutathione levels are likely
to live the longest in the best of health. A number of ways have been
demonstrated to increase glutathione (GSH) and the glutathione enzymes,
glutathione peroxidase (G-Px) and glutathione reductase (GR).
Several small studies have shown that moderate, prolonged physical
exercise increases glutathione and its related enzyme levels in the
blood and skeletal muscles.19,20
Many vitamins and nutritional supplements are also glutathione
boosters. Lipoic acid, pine bark extract (pycnogenol), melatonin,
bilberry, grape extract, and turmeric have all been shown to elevate
glutathione. Oral glutamine may also raise tissue glutathione levels,21
although there are conflicting reports.22
I used to think that oral glutathione was destroyed in the stomach, and
was not effective in raising glutathione concentrations. However, Dr.
Steve Edelson, of the Edelson Center for Environmental and Preventive
Medicine in Atlanta, Georgia, kindly sent me a number of articles that
convinced me otherwise. These articles demonstrated that about 80
percent of oral glutathione is absorbed intact, and that the blood
levels remain elevated for about three hours (Fig. 6).23-26
Foods that are high in glutathione include horseradish and cruciferous
vegetables such as cauliflower, broccoli, cabbage, kale, and brussels
sprouts. Dietary supplements that have been demonstrated to predictably
raise blood glutathione levels are the glutathione precursors whey
protein,5,27,28 and N-acetylcysteine (in a dose of 1,800-2,400 mg
daily),12 or (as mentioned above) glutathione itself (recommended dose,
1-2 grams daily). A prudent person would probably use a combination of
these modalities.
Many physicians are also using intravenous infusions of glutathione,
ranging in dosages of 400-600 mg three to seven days a week for a
number of conditions, including Parkinson?s and Alzheimer?s
diseases, strokes, ALS, and other chronic degenerative diseases.29
Based on the work of Drs. Lang, Richie, Buonous, Perlmutter, and
others, it appears that glutathione and its precursors should be used
for the prevention and treatment of virtually every chronic
degenerative disease.
------------------------------------------------------------------------
http://www.eurekalert.org/pub_releases/2006-08/uoc--uss072706.php
The August 1, 2006 issue of the journal Clinical Cancer Research
published the finding of researchers at UCLA that a greater ratio of
omega-3 to omega-6 fatty acids in the diet was associated with a
reduction in prostate tumor growth rates and prostate-specific antigen
(PSA) levels in a mouse model of hormone-sensitive prostate cancer.
Omega-3 fatty acids consist of EPA and DHA, found in oily fish and the
algae that they feed on, and ALA, found in flax and other plants.
Omega-6 fatty acids are found mainly in vegetable oils such as those
derived from corn and safflower, and are also found in red meat.
David Geffen School of Medicine department of urology professor William
Aronson and colleagues used immunodeficient mice injected with human
prostate cancer cells for the current study.
One group of mice was provided with a diet that contained 20 percent
fat consisting of a 1 to 1 ratio of omega-3 to omega-6 fatty acids,
while a second group received the same diet with its 20 percent fat
content consisting mostly of omega-6 fatty acids. The animals'
weights and tumor volumes were measured weekly. After eight weeks the
animals' tumors were examined and blood serum was analyzed for PSA.
The research team found a 22 percent average reduction in tumor cell
growth rates and 77 percent lower PSA levels among mice who received
the omega-3 fatty acids compared to animals whose dietary fats were
predominantly omega-6. Pro-inflammatory prostaglandin (PGE-2) levels
were 83 percent lower in the tumors of mice who received the high
omega-3 diet than in mice on the omega-6 fatty acid diet.
An increased omega-3 to omega-6 fatty acid ratio results in higher
tumor EPA and DHA content and a reduction in arachidonic acid. These
fatty acids compete to be converted by cyclooxgenase enzymes (COX) into
prostaglandins, which can become either pro-inflammatory or
anti-inflammatory and reduce growth. Higher levels of DHA and EPA may
lead to development of more anti-inflammatory prostaglandins.
The study is among the first to demonstrate the effect of reducing a
prostate cancer- promoting inflammatory response via diet. Dr Aronson
commented, "Corn oil is the backbone of the American diet. We consume
up to 20 times more omega-6 fatty acids in our diet compared to omega-3
acids. This study strongly suggests that eating a healthier ratio of
these two types of fatty acids may make a difference in reducing
prostate cancer growth, but studies need to be conducted in humans
before any clinical recommendations can be made."
"We may be able to use EPA and DHA supplements while also reducing
omega-6 fatty acids in the diet as a cancer prevention tool or possibly
to reduce progression in men with prostate cancer," Dr Aronson added.
The team is currently conducting a trial which will compare the effects
of a low-fat diet supplemented with omega-3 fatty acids to those of a
balanced Western diet on men whose prostate glands were removed due to
prostate cancer.
Health Concern-Prostate cancer
Eicosanoids are hormones that are made within the cell membrane of each
and every cell--all 60 trillion cells in the human body. Eicosanoids
are 20-carbon structures.
Eicosanoids have autocrine, paracrine, and endocrine effects. That is,
they affect the very cell that produces the eicosanoid (autocrine
effect), as well as nearby cells (paracrine effect) and distant cells
(endocrine effect). As with every aspect of biology, balance is a
critical issue relating to good health as well as the development and
progression of various diseases. Likewise, eicosanoid balance plays a
central role that puts this desired biological endpoint at the hub of
the integrative medicine wheel.
Eicosanoids, and the balance of good versus bad eicosanoids, can be
seen as the heart and soul, muscle, bone, and sinew, literally and
figuratively, of holistic medicine.
Clearly pertinent to a discussion of prostate cancer (PC) is the fact
that the first eicosanoids isolated in 1936 by Ulf von Euler were
prostaglandins--eicosanoids isolated from the prostate gland.
Eicosanoids are the oldest hormones, tracing their origin back 500
million years ago to production by sponges. Hormones are messengers
involved in communication between cells. A hormone is formally defined
as a substance, usually a peptide or steroid, produced by one tissue
and conveyed by the bloodstream to another to affect physiological
activity, such as growth or metabolism.
Eicosanoid synthesis involves the release of arachidonic acid (AA) from
cell membrane phospholipids by an enzyme called phospholipase A2
(PLA2). AA then undergoes metabolism by cyclooxygenases (COXs) and
lipoxygenases (LOXs). AA is an omega-6 fatty acid that is known to
generate free radicals and is considered an unfavorable eicosanoid.
Specific metabolites of AA, for example, PGE2 and 5-HETE, are created
through the actions of the enzymes COX-2, 5-LOX, 12-LOX, and 15-LOX.
These metabolites are examples of bad eicosanoids and have been
implicated in PC growth and metastasis. In a study of human PC in which
5-LOX and its metabolite 5-HETE were evaluated in both malignant and
benign prostate tissue within the same patient, both 5-LOX and 5-HETE
were significantly overexpressed in the PC tissue.
In other words, specific eicosanoids are modulators of tumor cell
interactions with certain host components within the context of cancer
growth, invasion, and spread.
EPA, an omega-3 fatty acid, has been shown to suppress AA formation by
inhibiting the enzyme delta-5-desaturase.
Some epidemiologic studies have shown that high intakes of EPA and DHA
lower PC risk substantially. Other studies have shown a reduction in PC
risk only with a decrease in the ratio of AA to EPA (AA:EPA). A
combination of GLA and EPA administered to humans was shown to strongly
increase serum EPA and DGLA levels and to reduce AA formation and AA
metabolites such as leukotrienes.
--------------------------------------------------------------------------------------------
What is an I.M.I.D. ?
This is a rePeat. Been here before, time to bring back.
http://www.medicalnewstoday.com/medicalnews.php?newsid=11029
Scientific and clinical aspects of the management of immune-mediated
inflammatory disorders (IMID)
Earlier diagnosis and more aggressive treatment of Immune-Mediated
Inflammatory Disorders (I.M.I.D.), such as rheumatoid arthritis,
multiple sclerosis and Crohn's disease, may offer the opportunity to
prevent some of the more severe manifestations, as well as the
progression of these diseases.
Overexpression of interleukin-12 (IL-12) and interleukin-23 (IL-23),
which share a common p40 receptor, may be significant to the
progression of a number of significant diseases such as multiple
sclerosis, Crohn's disease, and psoriasis. In addition, the
pro-inflammatory and immuno-stimulatory cytokine IL-6 may have crucial
impact in rheumatoid arthritis and lupus as well as some cardiovascular
and metabolic disorders, according to recent immunologic data.
"The IL-12 family of cytokines plays an important role in bridging both
innate and adaptive immune responses," says Scott Plevy, MD. "It is
therefore not surprising that deregulation of IL-12 function could
contribute to the pathophysiology of I.M.I.D." Dr. Plevy is an
associate professor of medicine and immunology at the University of
Pittsburgh School of Medicine in Pittsburgh, Pennsylvania. He has
extensive clinical and research experience related to inflammatory
bowel disorders.
The role of tumor necrosis factor alfa (TNF-alpha) in stimulating
I.M.I.D. is already widely recognized. According to Albert Lasker
Clinical Medical Research Award winner Professor Marc Feldmann, MD,
PhD, "Induction of tumor necrosis factor influences many biological
effects that are related to a wide range of Immune-Mediated
Inflammatory Disorders, including rheumatoid arthritis, psoriasis,
Crohn's disease, and numerous other life-limiting diseases. By blocking
the effects of TNF, we are learning how to treat a number of I.M.I.D.,
and our increasing knowledge is allowing us to gain a greater
appreciation of the way these diseases can be recognized and
potentially managed in the future. Most importantly, TNF blockade can
protect from tissue damage and promote healing of joints in rheumatoid
arthritis and of fistulas in Crohn's disease."
Feldmann is professor and head of the Kennedy Institute of Rheumatology
Division, Imperial College London and head of the Institute's Cytokine
Biology and Cellular Immunology Group.
The term I.M.I.D. refers to a group of biologically interconnected
diseases that share common inflammatory pathways and are characterized
by immune dysregulation that results in acute or chronic inflammation,
causing injury to the body. I.M.I.D. includes disorders as diverse as
autoimmune conditions, some forms of cancer, some infectious diseases,
and a variety of other chronic conditions that are the consequence of
inflammation of selected tissues. While these diseases may appear very
different, they may be caused by dysfunction in similar physiologic
pathways.
Collectively, I.M.I.D. may affect between 5% and 7% of the western
world's population, and as many as one in four patients admitted to
hospitals in the U.S. suffers from an I.M.I.D. By identifying the
molecular targets that trigger these disorders and developing new
pharmaceutical and biopharmaceutical therapies, it should be possible
to improve the lives of the patients most severely affected.
The Federation of Clinical Immunology Societies (FOCIS), an
international "think tank" in clinical immunology, has designated funds
and expertise to selected medical and clinical research centers to
explore diseases of immune dysregulation from a basic research,
translational research, and clinical science perspective.
The FOCIS Centers of Excellence are organized to intensify and
accelerate multidisciplinary scientific and clinical innovation,
education, and advocacy in the field of clinical immunology. This
concept encourages the opportunity for specialists in a variety of
fields (gastroenterology, rheumatology, immunology, and other areas of
specialty) to collaborate in seeking to advance our understanding of
the underlying relationship among their disparate diseases, and to
correlate that information with practical guidance on the management of
these devastating diseases.
Plevy and Feldmann, together with Mercedes RincĆ³n, PhD (University of
Vermont, College of Medicine, Burlington, VT) will speak at a special
session on "Pleiotropic Cytokines in Immune-Mediated Inflammatory
Disorders: From the Bedside to the Bench," held on July 21, 2004 during
the 12th International Congress of Immunology and the 4th Annual
Conference of the Federation of Clinical Immunology Societies (FOCIS)
in Montreal, Canada. The educational session is co-sponsored by FOCIS
and McGill University, and is supported by an educational grant from
Centocor, Inc
____________________________________________--
randall... plenty of hoPe? Either self responsive or a drug?
randall
Saved this one for right here. There was far to much stuff in that
100th post to the P news thread.
OK. Eureka time now.
Is this our salvation? WE just need to grow our T reg cells with booze?
In vitro,
http://en.wikipedia.org/wiki/In_vitro
Not in vivo,
http://en.wikipedia.org/wiki/In_vivo
I'm hearing a huge sigh? I know most of you have been trying this in
vivo. LOL
Get them thar T cells drunk? They grow like crazy and we reimplant
them to turn off the immune response?
Read on. It may be true. Strange as it sounds.
http://news.biocompare.com/newsstory.asp?id=146596
Finding Paves Way For Better Treatment Of Autoimmune Disease
8/8/2006
Source: Medical College of Georgia
A signaling molecule with an affinity for alcohol has yielded a rapid,
inexpensive way to make large numbers of immune cells that work like
beat cops to keep misguided cells from attacking the body.
The ability to easily make large numbers of these cells opens the door
to improved treatment and a better understanding of autoimmune diseases
such as type1 diabetes and arthritis, Medical College of Georgia
researchers say.
T cells are components of the immune system designed to attack invaders
such as bacteria and viruses; regulatory T cells are a small subset
that prevents the cells from also attacking body tissue.
Research published in the August issue of Nature Methods shows that,
given the option, phospholipase D, which typically mixes with water,
prefers alcohol. It's an apparently lethal choice for the signaling
molecule that, in turn, also kills T cells that need phospholipase D to
survive. Previously, it was unknown whether regulatory T cells required
the molecule.
"What we have found is that if you block this enzyme, almost all T
cells die after three days but the regulatory T cells can survive,"
says Dr. Makio Iwashima, MCG immunologist and the study's
corresponding author. "After three days, we give them some food to
grow and, in one week, you get about 90 percent pure regulatory
cells."
The approach worked with laboratory-grade alcohol, called butanol, as
well as beverage-grade ethanol.
Normally, regulatory T cells constitute about 2-5 percent of all T
cells, Dr. Iwashima says. Isolating them is doable but a long,
expensive process.
When researchers gave some of the regulatory T cells to a mouse model
of inflammatory bowel disease, the symptoms, including dramatic weight
loss, went away. Animals showed no classic signs of inflammation, just
a significant increase in regulatory cells.
MCG researchers have obtained funding from the Arthritis Foundation and
the Juvenile Diabetes Research Foundation to see if the cell therapy
will work as well in animal models for arthritis and type 1diabetes.
"Our prediction and our hope is that we can restore balance," says
Dr. Iwashima. The usual 5- to 95-percent ratio of regulatory cells to
non-regulatory T cells is lost in those with autoimmune disease, he
says. However, too many regulatory cells also can be a problem, he
says, noting that cancer patients have higher levels of regulatory
cells.
Regulatory T cell therapy also resolved symptoms in a model of graft
versus host disease, a problem for some bone marrow transplant patients
when immune cells from the donor start attacking. This finding
indicates a potential role for helping transplant patients keep new
organs, the researchers say.
Dr. Iwashima has an Alcoholic Beverage Medical Research Foundation
grant to pursue alcohol's potential for helping isolate desirous
regulatory cells. However, he cautions that his research findings are
not a green light for patients with autoimmune disease to drink because
of the negative health effects of regular alcohol consumption.
Dr. Iwashima and his colleagues believe the best way to optimize cell
percentages is to do what the body does. In fact, they already are
searching for an endogenous substance that interferes with
phospholipase D.
"Ultimately, that is the most natural way, if we can find the
compound in our bodies that can do the job," Dr. Iwashima says. He
theorizes that this natural substance helps destroy non-regulatory T
cells when the body gets too many, say after fighting a big infection,
and that it may not work well enough in people with autoimmune disease.
The research was supported by the National Institutes of Health
====================================================
OK. If it works we keep our T regs drunk 24/7.
Yet, P genes are still the main target we've heard.
Combinatorial control of genes (from the first story in the p news post
today)
http://en.wikipedia.org/wiki/Gene_regulation
===================================
I like the drunk T reg cell theory better!
Those gene things look really comPlicated.
randall... alcohol, weaPon of MASS destruction, pass the wine!
randall
That last post was looking really good. I'm getting excited now.
Having a chronic slow burn inflammatory condition like P, it took
me a few minutes to read and reread that last story for it all to
sink in.
Let's find some more related links to it.
http://www.eurekalert.org/pub_releases/2006-08/mcog-fpw080806.php
The breaking story was on the MCG site on August 4th?
http://www.mcg.edu/news/2006NewsRel/Iwashima080406.html
It's like a Dr. Makio tsunami since this story broke,
http://www.google.com/search?hl=en&lr=&q=Dr.+Makio+Iwashima%2C+immunologist&btnG=Search
I wonder how soon this will be used to cure us?
I know i'm jumPing the gun. And i can't understand why i didn't pick it
up
sooner. But this may be the break we're all waiting for.
randall... in the Pink, give them T regs a drink!
randall
Someone finally found that one molecule that TWEAK'S the immune system.
So that's what they called it?
Now you know. All psoriatics are tweaker's. lol
So.
StoP the tweaking already.
http://www.tradingmarkets.com/tm.site/news/BREAKING%20NEWS/342550/
Biogen Idec Says Inhibition Of TWEAK Molecules May Lead To Rheumatoid
Arthritis Treatment - Update
Tuesday, August 15, 2006; Posted: 12:30 PM
RTTNews) - Tuesday morning, Biogen Idec Inc. (BIIB | charts | news |
PowerRating) engaged in the development, manufacture and
commercialization of therapies primarily in the areas of oncology,
neurology and immunology reported that the activation of the recently
discovered inflammation pathway may play an important role in the
disease process that lead to rheumatoid arthritis. The report published
in the Journal of Immunology says that the inhibiting the TWEAK
molecule may provide a new approach to developing rheumatoid arthritis
treatments.
Rheumatoid Disease is an autoimmune disease that causes chronic
inflammation of the joints. It can cause inflammation of the tissues
around the joints, as well as other organs in the body. It is found
that the inflammations are caused when the body tissues are mistakenly
attacked by its own immune system, hence the name auto immune disease.
The disease can lead to long-term damage, loss of function and
disability. In the advanced stage, the disease can cause progressive
damage to the cartilage and bone. Currently the cause of rheumatoid
arthritis is unknown and 2.1 million US citizens are affected by the
disease.
The Cambridge, Massachusetts-based company revealed that TWEAK was
discovered by its own research wing in collaboration with the
scientists at University of Geneva. The report further says that TWEAK
belongs to a family of molecules known as tumor necrosis factor that
plays an important role in normal immune system and inflammatory
responses. Currently, therapies targeting inhibition of tumor necrosis
factor are in use for the treatment of a number of diseases including
rheumatoid arthritis.
The report further says that the TWEAK stimulates blood vessel growth
or angiogenesis and production of inflammatory proteins called
cytokines and chemokines. TWEAK can promote joint inflammation and
synovial angiogenesis or blood vessel growth in joints that are
described as hallmarks of arthritis.
The study recorded that TWEAK can stimulate the production of several
types of inflammatory proteins that can promote joint inflammation.
Scientists believe that TWEAK can impede normal bone repair mechanisms.
Tweak can triggers joint damage by stimulating the production of
damaging metalloprotease enzymes and promoting bone breakdown, and
contributes to joint tissue disease by directly promoting angiogenesis
in synovial tissue, the study reveals.
Commenting on the discovery, Timothy Zheng, Senior Scientist, Molecular
Discovery at Biogen Idec said "Despite considerable progress, many
rheumatoid arthritis patients do not adequately respond to current
treatments, indicating that other pathways are involved in this complex
disease. Our investigative research suggests that TWEAK contributes to
the disease through multiple mechanisms, and inhibiting the TWEAK
pathway may represent a new set of opportunities for treatment."
BIIB is currently trading at $42.22 up $0.39 or 0.93% on a volume of
1.16 million share
-------------------------------------------------------------------------------
Great it's true, we are tweaker's.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16888023&query_hl=26&itool=pubmed_docsum
TWEAK Is a Novel Arthritogenic Mediator.
* Perper SJ,
* Browning B,
* Burkly LC,
* Weng S,
* Gao C,
* Giza K,
* Su L,
* Tarilonte L,
* Crowell T,
* Rajman L,
* Runkel L,
* Scott M,
* Atkins GJ,
* Findlay DM,
* Zheng TS,
* Hess H.
Biogen Idec, Cambridge, MA 02142.
TNF-like weak inducer of apoptosis (TWEAK) is a TNF family member with
pleiotropic effects on a variety of cell types, one of which is the
induction of proinflammatory cytokines by synovial fibroblasts derived
from rheumatoid arthritis (RA) patients. In this study, we report that
the serum TWEAK level was dramatically elevated during mouse
collagen-induced arthritis (CIA) and blocking TWEAK by a neutralizing
mAb significantly reduced the clinical severity of CIA. Histological
analyses also revealed that TWEAK inhibition diminished joint
inflammation, synovial angiogenesis, as well as cartilage and bone
erosion. Anti-TWEAK treatment proved efficacious when administered just
before the disease onset but not during the priming phase of CIA.
Consistent with this, TWEAK inhibition did not affect either cellular
or humoral responses to collagen. In contrast, TWEAK inhibition
significantly reduced serum levels of a panel of arthritogenic
mediators, including chemokines such as MIP-1beta (CCL-4), lymphotactin
(XCL-1), IFN-gamma-inducible protein 10 (IP-10) (CXCL-10), MCP-1
(CCL-2), and RANTES (CCL-5), as well as the matrix metalloprotease-9.
Exploring the possible role of the TWEAK/Fn14 pathway in human RA
pathogenesis, we showed that TWEAK can target human primary
chondrocytes and osteoblast-like cells, in addition to synovial
fibroblasts. We further demonstrated that TWEAK induced the production
of matrix metalloproteases in human chondrocytes and potently inhibited
chondrogenesis and osteogenesis using in vitro models. These results
provide evidence for a novel cytokine pathway that contributes to joint
tissue inflammation, angiogenesis, and damage, as well as may inhibit
endogenous repair, suggesting that TWEAK may be a new therapeutic
target for human RA.
PMID: 16888023
-------------------------------------------------
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16887827&query_hl=26&itool=pubmed_docsum
IKK{beta}/2 induces TWEAK and apoptosis in mammary epithelial cells.
* Baxter FO,
* Came PJ,
* Abell K,
* Kedjouar B,
* Huth M,
* Rajewsky K,
* Pasparakis M,
* Watson CJ.
Department of Pathology, University of Cambridge, Tennis Court Road,
Cambridge CB2 1QP, UK.
The Nuclear Factor-kappaB (NF-kappaB) family of transcription factors
are ubiquitously expressed and control a wide range of cellular
responses, including apoptosis, proliferation, differentiation,
inflammation and immunity. Here, we investigated the function of the
NF-kappaB upstream regulator IkappaB kinase 2/beta (IKK2) in apoptosis
regulation in the normal physiological setting of regressing mammary
gland. Conditional deletion of the gene encoding IKK2 resulted,
surprisingly, in delayed apoptosis and remodelling, and abrogation of
caspase 3 cleavage. This failure to induce involution was associated
with reduced expression, within 24 hours of involution, of the death
receptor (DR) ligand TNF and its receptor TNFR1, which are known
NF-kappaB targets. This was associated with elevated levels of active
AKT and phosphorylated FOXO3a. Furthermore, we show that expression of
TWEAK, another DR ligand, is dramatically downregulated, even in
heterozygous IKK2 mammary glands. Unlike other DR ligands, the TWEAK
promoter has six consensus FOXO-binding sites, further suggesting that
it is differentially regulated. Interestingly, a cleaved form of TWEAK
is upregulated during involution. This unexpected function of the
IKK2/NF-kappaB pathway as a regulator of TWEAK expression and inducer
of apoptosis has significant consequences for future therapeutic
approaches for cancer and inflammatory diseases.
PMID: 16887827
---------------------------------------------------------------------------
http://www.upi.com/NewsTrack/view.php?StoryID=20060815-115155-3035r
Autoimmune brain inflammation studied
SAN FRANCISCO, Aug. 15 (UPI) -- U.S. scientists say a key factor in
development of brain inflammation may provide a new target for
inflammatory diseases of the central nervous system.
In separate studies, Nico Ghilardi of Genentech Inc. in San Francisco
and Christopher Hunter of the University of Pennsylvania studied
different mouse models of brain inflammation that resemble human
diseases, such as multiple sclerosis.
Both studies show brain inflammation is worse in mice that cannot
respond to interleukin 27, a factor that communicates messages to
immune cells. Such increased brain inflammation is associated with an
influx of T cells that produce a molecule known to promote inflammation
-- interleukin 17 -- into the brain.
The researchers found treatment of T cells with interleukin 27 blocks
the development of cells that produce interleukin 17.
Therefore, the scientists posit preventing harmful interleukin
17-producing cells from developing, interleukin 27 could represent a
potential therapeutic target for treating autoimmune diseases.
The study appears in the journal Nature Immunology.
randall... the last few days have me tweaking my brains out. Skin is
better!
randall
Can P38 save us? It does solve PV (pemphigus vulgaris) in mice.
Humans with PV (psoriasis vulgaris) lining up next?
http://www.newswise.com/articles/view/522945/
Newswise - Skin is our first line of defense against infection. But
people with a rare, life-threatening autoimmune disease called
pemphigus vulgaris lack that protection because their immune system
attacks the proteins that hold skin cells together. They develop severe
blisters and raw sores as the top layer of their skin falls apart,
leaving them extremely vulnerable to infection.
The development of drugs that completely suppress the immune system
offered a lifeline to patients with pemphigus vulgaris (PV) and other
autoimmune disorders, but the drugs themselves can be lethal and often
cause serious side effects.
Now, researchers at the University of North Carolina at Chapel Hill
have found a safer, more effective way to treat PV patients. In mice,
the researchers used a known compound to turn off the signals that
trigger skin damage without suppressing the immune system. Similar
drugs being developed for human use could offer a potential treatment
for PV, the researchers said.
The results appear in the Aug. 22 issue of Proceedings of the National
Academy of Sciences. The research was funded the National Institutes of
Health.
"Even if we can't block the immune response, if we can understand
the mechanisms behind the damage it causes, we can block that
damage," said Dr. David S. Rubenstein, associate professor in the
departments of dermatology and pathology in the UNC School of Medicine
and a member of the UNC Lineberger Comprehensive Cancer Center.
"Targeting these specific events in the cell could enable us to more
effectively and safely treat patients."
Rubenstein has previously shown an enzyme called p38 is part of the
mechanism by which pemphigus vulgaris autoantibodies cause damage.
Autoantibodies are immune-system cells that attack the body's own
tissues.
In a mouse model of pemphigus vulgaris, the researchers prevented
blistering and other signs of the disease by injecting a drug that
inhibits the p38 enzyme. Tests showed that the p38 inhibitor drug
didn't prevent autoantibodies from binding to the skin cells.
Instead, it prevented them from damaging the skin as they normally do.
The drug stopped a series of cell-signaling events that lead to the
loss of adhesion or "stickiness" between skin cells. Thus, it stops
the disease without affecting the immune system.
"There are a number of companies developing inhibitors of the p38
enzyme for treating rheumatoid arthritis and psoriasis," Rubenstein
said. "Our study suggests that those same drugs might be valuable in
treating pemphigus vulgaris."
Of the 48 mice used in the study, 24 received a high dose of
autoantibody which causes gross blistering akin to human PV. The other
group of 24 received a lower dose that would cause less severe
blistering. Half of each group also received treatment with a p38
inhibitor.
In the two groups that received p38 inhibitor treatment, almost no mice
showed clinical signs of pemphigus vulgaris. For instance, in the group
that received the high dose of pemphigus vulgaris antibody, 11 out of
12 mice showed blistering, but of the 12 mice that received also
received the p38 inhibitor, only one showed blistering.
UNC School of Medicine co-authors include research analyst Paula
Berkowitz, research assistant professor Dr. Peiqui Hu, professor Dr.
Luis A. Diaz and associate professor Dr. Zhi Liu, all of the department
of dermatology; and Dr. Simon J. Warren, assistant professor in the
departments of dermatology and pathology.
-------------------------------------------------------
H'mmm,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%p38+psoriasis
OH! LOOky1
#2 in this list not only blocks mapk but also LPS. How about that.
My theory is still alive. And for that matter so is Mikhails.
Lets look at #2,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16702443&query_hl=14&itool=pubmed_docsum
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., P.O. Box 5350, Princeton, NJ
08543-5350, USA.
The p38 mitogen-activated protein (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
[3-(4-(1,4-diazepan-1-yl)-6-(((1S,2R,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)methylamino)-1,3,5-triazin-2-ylamino)-4-methylbenzamide],
a representative compound identified from screening a collection of
combinatorial libraries, amounting to 2.1 million compounds, inhibits
p38alpha kinase and the lipopolysaccharide (LPS)-induced increase in
tumor necrosis factor (TNF) alpha levels in cell media of human
monocytes with IC50 values of 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 p38 gamma
and is >25-fold selective versus a panel of other kinases. PS200981
inhibited the LPS-induced increase in TNFalpha levels when administered
at 30 mg/kg to mice. Selectivity and in vivo activity of this class of
p38 inhibitors was further demonstrated by PS166276
[(R)-3-(4-(isobutyl(methyl)-amino)-6-(pyrrolidin-3-ylamino)-1,3,5-triazin-2-ylamino)-4-methylbenzamide],
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 love to be vindicated. But i'd love to be cured even more. :)
randall...
JXStern
>Can P38 save us? It does solve PV (pemphigus vulgaris) in mice.
http://www.kemia.com/brandomatic/templates/kemia.htm
Sounds to me like it's too far downstream, fights inflammation but
doesn't block the trigger. Still, apparently it might be applied
topically, that's something, I guess.
http://www.aviation-history.com/lockheed/p38.html
Now, *that* might work!
J.
randall
JXStern wrote:
> On 22 Aug 2006 19:31:12 -0700, "randall" <ranh...@aol.com> wrote:
> >Can P38 save us? It does solve PV (pemphigus vulgaris) in mice.
>
> http://www.kemia.com/brandomatic/templates/kemia.htm
Let's post it:::
KĆ©mia, Inc. discovers and develops novel small molecule therapeutics.
KĆ©mia focuses on high value disease targets that are validated but not
yet addressed by safe and effective non-injectable drugs. KĆ©mia's
competitive advantage includes proprietary chemistries, a
multi-disciplinary approach to medicinal chemistry integrated with
rigorous ADME and pharmacokinetic evaluation, and an experienced
development team.
KĆ©mia has successfully completed Phase I human clinical trials on its
first compound, KC706, an orally active allosteric p38 MAP kinase
inhibitor being developed for the treatment of inflammatory diseases
such as rheumatoid arthritis. KC706 was shown to have an excellent
safety profile. A Phase II clinical trial in rheumatoid arthritis
patients is scheduled to start early in the third quarter of 2006. A
second drug from this program, delivered topically, will enter the
clinic in early 2007. The topical drug is being developed for the
treatment of inflammatory skin diseases such as psoriasis.
KĆ©mia's proprietary chemistries represent two important classes of
therapeutic agents: allosteric kinase inhibitors and modulators of G
protein-coupled receptors (GPCRs). In addition to its two clinical
stage programs, KĆ©mia has promising programs at earlier stages of
development: CCR5 inhibitors (HIV) and amylin receptor agonists
(diabetes/obesity). KĆ©mia has demonstrated it can generate potent and
selective lead compounds for each of these targets.
>
> Sounds to me like it's too far downstream, fights inflammation but
> doesn't block the trigger. Still, apparently it might be applied
> topically, that's something, I guess.
>
> http://www.aviation-history.com/lockheed/p38.html
>
> Now, *that* might work!
>
> J.
Hey J,
P38 or P51 as long as it's fun and we're in the wild blue yonder
looking for CLEAR skies. Oral, injectible, transdermic, hypodermic.
who cares if it's a cure.
Kemia goes public today. Thanks for the link btw.
August 23, 2006 11:00 AM US Eastern Timezone
Kemia Announces Completion of Phase I Trials for Oral Anti-Inflammatory
Drug; KC706, a p38 MAP Kinase Inhibitor, Targets Inflammatory
Conditions Including Arthritis, Psoriasis, and Cardiovascular Disease
SAN DIEGO--(BUSINESS WIRE)--Aug. 23, 2006--Kemia announced today that
the company has completed initial Phase I clinical trials with KC706, a
novel oral anti-inflammatory drug that works by selectively and
allosterically inhibiting p38 MAP kinase. Based on these successful
Phase I trials, Kemia now plans to evaluate KC706 in several diseases
characterized by chronic inflammation. The first Phase IIa clinical
trial, treating patients suffering from rheumatoid arthritis, will
commence at the end of September.
"We are pleased with the clinical profile that is emerging for KC706,"
said Lew Shuster, Kemia's CEO. "We are excited about the prospects of
Kemia's first new medicine, which was designed and synthesized in
Kemia's drug discovery group and then brought through Phase I trials by
Kemia's development team. We will be aggressively pursuing its
continued clinical development with our upcoming Phase II trials."
An initial escalating single-dose study in healthy human volunteers
showed that KC706 was well tolerated. A second, escalating
multiple-dose study evaluated the human pharmacokinetics of KC706 and
demonstrated the safety of a range of doses to be used in Phase II
clinical trials. A third Phase I trial confirmed the bioavailability of
a capsule formulation to be used in future trials. A total of 79
healthy volunteers have received the drug to date. One assay conducted
as part of the Phase I trials confirmed that KC706 was providing a
long-acting, dose-dependent anti-inflammatory effect.
KC706 may hold the potential to treat inflammatory conditions such as
rheumatoid arthritis, psoriasis, asthma, chronic obstructive pulmonary
disorder, and certain metabolic and cardiovascular diseases. The
company will shortly commence enrolling a placebo-controlled Phase IIa
clinical trial in Europe in 150 patients with rheumatoid arthritis. The
safety and efficacy of two doses of KC706 will be evaluated over a
12-week dosing period in patients who have evidence of active
rheumatoid arthritis in spite of ongoing therapy with methotrexate. The
company is now planning another Phase IIa trial to explore the
potential for KC706 in a second disease area.
Kinases are key regulatory proteins in important biological pathways
such as inflammation. Kemia's chemistries represent a "next generation"
approach in contrast to the majority of earlier generation kinase
inhibitors that directly compete for ATP binding. Kemia believes that
the allosteric inhibitors developed by Kemia offer improved selectivity
compared to first generation ATP competitive compounds and thus should
reduce the risk of side effects from off-target interactions.
KC706 is a selective, allosteric p38 MAP kinase inhibitor. The p38
protein is an important signaling molecule in inflammation. High levels
of p38 activity have been associated with several inflammatory
diseases. Additionally, the allosteric binding of KC706 to p38 MAP
kinase results in a much longer duration of action compared to
traditional ATP-competitive kinase inhibitors. This extended binding
with the target protein provides the potential for once-daily dosing to
have a more sustained therapeutic effect.
In addition to the oral KC706 program, Kemia is exploring additional
formulations of the KC706 including a topical formulation to treat
psoriasis. Other, earlier stage programs at the company include
inhibitors of CCR5 for the treatment of HIV and inflammatory conditions
and amylin receptor agonists for the treatment of obesity and diabetes.
Kemia's amylin receptor agonists are non-peptide small molecules with
the future potential for oral dosing. In animal models, they slow
gastric emptying and decrease food intake similarly to the injectable
hormone they are designed to mimic. Kemia believes the longer duration
of action of a small molecule drug should result in a superior weight
loss benefit to patients.
About Kemia, Inc.
Kemia discovers and develops novel small molecule therapeutics. Kemia
focuses on high value disease targets that are validated, but not yet
addressed by safe and effective non-injectable drugs. Kemia's
competitive advantage includes proprietary chemistries for allosteric
inhibition of kinases and for modulation of GPCRs (G-protein coupled
receptors), a multi-disciplinary approach to medicinal chemistry, and
rigorous ADME and pharmacokinetic evaluation integrated into the lead
optimization process. For more information about Kemia please visit
www.kemia.com.
NOTE TO EDITORS: In the company name Kemia Inc. noted in this news
release, there is an accent over the "e" in "Kemia."
===========================================
The P38 mapK inhibitor thing is flying around like crazy the last few
days.
On to chaperonin 10 from OZ.
A protein that naturally fights inflammation in the body could be the
key to relief for arthritis sufferers, Australian researchers have
discovered.
A study by Melbourne, Perth and Brisbane scientists has found that
injecting high doses of an anti-inflammatory drug can "turn down" the
overactive immune systems of people with rheumatoid arthritis.
The discovery, detailed in the latest issue of the international
journal The Lancet, is being heralded as a long-awaited breakthrough in
the field.
The protein, known as chaperonin 10, works naturally in everybody to
fight off inflammation when it initially flares up.
In people with rheumatoid arthritis, the overactive immune system
attacks the tissues lining the joints, leading to painful inflammation,
heat and swelling.
Queensland biotech company CBio have created a drug containing the
protein which was tested on 23 people with moderate to severe forms of
the disease.
The compound was injected intravenously twice a week over three months
and was found to be "safe and effective".
All volunteers experienced improvements, with patients on the highest
doses of the drug up to 70 per cent improved after treatment.
And 13 per cent of patients effectively went into remission.
"What we've shown is that by giving extra chaperonin 10 to people who
suffer from this disease, we can essentially limit this malfunction,"
CBio chief executive Dr Wolf Hanisch said.
"It's exciting to now know it definitely works in humans."
While still in the early stages of development, the compound may prove
more effective than new-age rheumatoid arthritis treatments known as
biological response modifiers, which can weaken the immune system, he
said.
Dr Hanisch hopes it could eventually be used to treat other auto-immune
conditions like the skin disease psoriasis.
Another trial of 40 people will start later this year to work out the
best dose size and when it should be administered, before large scale
trials begin.
============================================
Chareronin 10? Its a heat shock protein.
Let's find it.
http://www-ermm.cbcu.cam.ac.uk/00002027h.htm
It's a 'double doughnut' structure with chap. 60. Must bind well.
Back to folding proteins? Or unfolding them?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12369934&query_hl=23&itool=pubmed_docsum
YeP,
http://en.wikipedia.org/wiki/GroEL
&
http://origins.swau.edu/papers/complexity/trilo/gifs/chaperonin.html
randall... i get off here please, time for takeoff.
JXStern
>Kemia goes public today.
Just financing, not trading, I think.
P38 has been under investigation for several years. Still it may
work, especially (drum roll) in a cocktail combo with other
treatments!
J.
randall
I like their page,
http://www.kemia.com/brandomatic/templates/topicalp38.htm
All the talk of curcumin lately, I may go back on it soon.
randall
randall
Since i've figured the gut is ground zero, wrongly or rightly it is
the one area i've made the most advances in clearing my own
psoriasis.
This area may one day be key to a cure for P.
For now using all that we can glean from current research isn't a bad
idea.
http://www.medicalnewstoday.com/medicalnews.php?newsid=50433&nfid=nl
Researchers at UT Southwestern Medical Center have identified a protein
that is made in the intestinal lining and targets microbial invaders,
offering novel insights into how the intestine fends off pathogens and
maintains friendly relations with symbiotic microbes.
The study, published today in the journal Science, might lead to new
medications aimed at helping patients with inflammatory bowel disease.
The findings might also aid in understanding the effectiveness of
probiotics - mixtures of beneficial bacteria that are added to food
products - in boosting the immune system, said Dr. Lora Hooper,
assistant professor of immunology and the paper's senior author.
Scientists have known for decades that microbial cells in the human gut
outnumber the body's own cells by about 10 to 1. Humans offer a safe
haven to these microbes because they help us to break down food that we
can't digest by ourselves. But it hasn't been clear how we keep these
microscopic gut dwellers from invading our tissues and causing
infections.
To help answer this question, Dr. Hooper's research team used mice
raised inside sterile plastic bubbles. Because they are never in
contact with the outer, microbe-filled world, these mice do not have
the bacteria that normally colonize the gut. By exposing these
"germ-free" mice to different types of gut bacteria, the researchers
were able to observe how the epithelial cells lining the intestine
react to microbial invaders.
"We found that when the gut lining comes into contact with bacteria, it
produces a protein that binds to sugars that are part of the bacterial
outer surfaces," Dr. Hooper said. "Once bound, these proteins quickly
destroy their bacterial targets. They're killer proteins with a sweet
tooth."
The protein, called RegIIIgamma in mice and HIP/PAP in humans, belongs
to a protein class called lectins, which bind to sugar molecules. These
particular lectins' seek-and-destroy mission may help to create an
"electric fence" that shields the intestinal surface from invading
bacteria, Dr. Hooper said.
The findings of this study may offer researchers new clues about the
causes of inflammatory bowel disease. Most healthy people have a
friendly relationship with their gut microbes, but in patients with
inflammatory bowel disease this tolerant relationship turns sour and
the immune system mounts an attack on the gut's microbial inhabitants
that can lead to painful ulcers and bloody diarrhea. What triggers this
attack is not clear, but the fact that these patients have elevated
HIP/PAP production suggests that they are coping with increased numbers
of invading intestinal bacteria.
The study may also help scientists devise more effective treatments for
intestinal infections. "We are now working to understand the mechanism
by which the intestinal lining senses bacterial threats. What turns
this protein antibiotic on?" Dr. Hooper asked. "We want to explore
whether this is something we can stimulate artificially to stave off
pathogenic infections."
###
Other contributors to the study, all from UT Southwestern's Center for
Immunology, are co-lead authors Heather Cash, a former graduate
student; and Cecilia Whitham, research assistant, and Cassie Behrendt,
research associate.
The research was supported by grants from the National Institutes of
Health, the Crohn's and Colitis Foundation of America, and a Burroughs
Wellcome Career Award in the Biomedical Sciences.
This news release is available on our World Wide Web home page at
http://www.utsouthwestern.edu/home/news/index.html
Dr. Lora Hooper -
http://www.utsouthwestern.edu/findfac/professional/0,2356,60931,00.html
Contact: Toni Heinzl
UT Southwestern Medical Center
---------
And the abstract to go along with it.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16931762&query_hl=2&itool=pubmed_docsum
Symbiotic bacteria direct expression of an intestinal bactericidal
lectin.
* Cash HL,
* Whitham CV,
* Behrendt CL,
* Hooper LV.
Center for Immunology, University of Texas Southwestern Medical Center
at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Lora....@UTSouthwestern.edu
The mammalian intestine harbors complex societies of beneficial
bacteria that are maintained in the lumen with minimal penetration of
mucosal surfaces. Microbial colonization of germ-free mice triggers
epithelial expression of RegIIIgamma, a secreted C-type lectin.
RegIIIgamma binds intestinal bacteria but lacks the complement
recruitment domains present in other microbe-binding mammalian C-type
lectins. We show that RegIIIgamma and its human counterpart, HIP/PAP,
are directly antimicrobial proteins that bind their bacterial targets
via interactions with peptidoglycan carbohydrate. We propose that these
proteins represent an evolutionarily primitive form of lectin-mediated
innate immunity, and that they reveal intestinal strategies for
maintaining symbiotic host-microbial relationships.
PMID: 16931762
Now i've got hip/pap to follow.
HiP hiP hooray for
Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein !
I know. It sounds like pap.
----------------------
Is Mucus in the Gi tract a good or bad thing?
http://www.medicalnewstoday.com/medicalnews.php?newsid=50288&nfid=nl
How Roughage Keeps You "Regular" Scientists Learn More
If you ever wondered just how a high-fiber diet helps keep you, well,
"regular," scientists may have the answer.
Their results suggest that as these bulky foods make their way down the
gastrointestinal tract, they run into cells, tearing them and freeing
lubricating mucus within.
More mucus is good, says Dr. Paul L. McNeil, cell biologist at the
Medical College of Georgia and corresponding author on the study
published online Aug. 21 and scheduled for the September print issue of
PloS Biology. "When you eat high-fiber foods, they bang up against the
cells lining the gastrointestinal tract, rupturing their outer
covering. What we are saying is this banging and tearing increases the
level of lubricating mucus. It's a good thing."
The fact that consuming roughage increases mucus production was known,
and years ago, Dr. McNeil discovered frequent cell injury and repair
occur when we eat.
The new research ties the two together.
"It's a bit of a paradox, but what we are saying is an injury at the
cell level can promote health of the GI tract as a whole," says Dr.
McNeil. Even though epithelial cells usually live less than a week,
they are regularly bombarded, in most of us at least three times a day
as food passes by. "These cells are a biological boundary that
separates the inside world, if you will, from this nasty outside world.
On the cellular scale, roughage, such as grains and fibers that can't
be completely digested, are a mechanical challenge for these cells,"
says Dr. McNeil.
But in what he and colleague Dr. Katsuya Miyake view as an adaptive
response, most of these cells rapidly repair damage and, in the
process, excrete even more mucus, which provides a bit of cell
protection as it eases food down the GI tract.
In research published in 2003 in Proceedings of the National Academy of
Sciences, Dr. McNeil showed proof of his then decade-old hypothesis
that cells with internal membranes use those membranes to repair
potentially lethal outer-membrane injuries. A recent paper published in
Nature in collaboration with Dr. Kevin Campbell's laboratory at the
University of Iowa showed how human disease, including certain forms of
muscular dystrophy, can result from a failure of this mechanism.
An outer membrane tear is like an open door through which calcium just
outside the cell rushes in. Too much calcium is lethal but that first
taste signals the vulnerable cell it better do something quick. With
epithelial cells, several of the internal mucus-filled compartments
fuse together within about three seconds, forming a patch to fix the
tear. In the process the compartments expel their contents so, almost
like a bonus, extra mucus becomes available to lubricate the GI tract.
"We have found a very natural way we can enhance mucus production,"
says Dr. Miyake, cell biologist and the study's first author. He and
Dr. McNeil suspected for years that mucus escaped cells as a result of
injury. "You might have predicted it, but science is about testing
predictions," says Dr. McNeil.
To test their theory, Dr. Miyake, co-director of MCG Cell Imaging Core
Laboratory, began working on a method to reproduce cell injuries. "Dr.
Miyake developed a very potent cutting edge technology involving the
two photon laser that allowed us to blast small holes in cells,
mimicking what happens in the living animal. It also allowed us to
assess in those living cells whether they could reseal, repair the
damage and how they might respond biologically, namely in this case,
whether they responded by secreting mucus as part of the healing
process," Dr. McNeil says.
They found time and again that most cells did just that, including
intact cells in a section of the GI tract. "Epithelial cells are
high-turnover cells but they have a built-in survivability," Dr. McNeil
says.
The scientists aren't certain how many times cells can take a hit, but
they suspect turnover is so high because of the constant injury.
Potentially caustic substances, such as alcohol and aspirin, can
produce so much damage that natural recovery mechanisms can't keep up.
But they doubt a roughage overdose is possible.
----------------------------
randall... these lectin things are making a come back!
randall
Bug enzyme for inflammation?
http://www.news.ucdavis.edu/search/news_detail.lasso?id=7858
Pest Control Research Leads to Pain Control Discovery
August 28, 2006
A newly discovered enzyme inhibitor, identified by researchers
originally looking for biological pest controls, may lead to pain
relief for sufferers of arthritis and other inflammatory diseases, say
researchers at the University of California, Davis. The finding, hailed
by a noted inflammatory disease expert "as the most important discovery
in inflammation in more than a decade," may also reduce side effects
associated with the pain killer Vioxx.
Lead author Kara Schmelzer, a post-doctoral researcher in principal
investigator Bruce Hammock's lab, tested the novel compounds on rodents
and found them to be as potent at a low-dose as Vioxx and Celebrex, but
without the changes in blood chemistry linked to heart attacks. Vioxx
and Celebrex belong to a class of drugs known as Cox-2 inhibitors. The
enzyme targeted by the newly discovered inhibitors is also found in
humans. (Enzymes are proteins that speed up chemical reactions.)
"The reason this is so exciting is that this is a novel way to reduce
inflammation, with a combination therapy," Schmelzer said. "We're going
after a new enzyme target, not going after the Cox-2 inhibitors."
Their research is reported in a paper entitled "Enhancement of
Antinociception by Coadministration of Nonsteroidal Anti-Inflammatory
Drugs and Soluble Epoxide Hydrolase Inhibitors," published in the
current edition of Proceedings of the National Academy of Sciences.
"Our laboratory was initially interested in regulating the development
of insect larvae," said Hammock, a distinguished professor of
entomology and member of the National Academy of Sciences. The
discovery switched the focus of the research from "pest control to pain
control."
M. Eric Gershwin, chief of the Division of Rheumatology, Allergy and
Clinical Immunology at the UC Davis School of Medicine and a
distinguished professor of medicine, called the discovery "the most
important discovery in inflammation in more than a decade." Gershwin,
who was not affiliated with this study, is noted for his research on
rheumatoid arthritis and other inflammatory diseases. His lab
investigates the mechanisms leading to immunological alterations and
autoimmunity.
As of 2004, physicians prescribed anti-inflammatory medication for more
than 73 million patients. But many of the people suffer from
pharmacological properties or side effects of the medications. Merck,
the pharmaceutical company that manufactured and marketed Vioxx, a
Cox-2 selective nonsteroidal anti-inflammatory drug (NSAID),
voluntarily pulled the pain killer from the market in September 2004
due to safety concerns. A 12-month study, published in 2000, showed a
four-fold increased risk of heart attacks. Merck hopes to replace it
with another medication, Arcoxia.
However, the class of drugs benefits millions of sufferers from
inflammation and pain, Hammock said. The UC Davis study may mean a
solution to the dilemma of whether to use the drugs.
"Combination therapies have long been used to treat inflammation while
reducing side effects," Schmelzer wrote. She said the present study was
designed to evaluate the therapeutic potential of combination treatment
with NSAIDs and enzyme inhibitors (a previously undescribed soluble
epoxide hydrolase inhibitor or sEHIs) in lipopolysaccharide
(LPS)-challenged mice.
"We used LPS as an inflammatory agent, which is a component of some
bacterial cell walls," said, co-author Steven Jinks. His laboratory
examined the effects of these compounds in rodent inflammatory pain
behavior models. "Inflammatory mediators sensitize pain receptors and
cause the animal to withdraw more quickly from a noxious stimulus, an
indication of 'hyperalgesia' or heightened response to a painful
stimulus. The sEH inhibitors reverse hyperalgesia and bring their
withdrawal reaction back into the normal range.
Hammock said "these sEHIs are of similar or greater potency in reducing
inflammation in rodents to Vioxx, but also when combined with Vioxx can
dramatically reduce the concentrations of the Cox 2 inhibitor needed,"
Hammock said.
"The combination of Vioxx with the new sEHIs shifts blood chemistry
toward the normal condition which may reduce the tendency toward blood
clots," said UC Davis scientist Bora Inceoglu, a post-doctoral
researcher and member of the research team.
Schmelzer, Inceoglu and Hammock teamed with: In-Hae Kim, post-doctoral
researcher in Hammock's lab; Steven Jinks, assistant adjunct professor,
Department of Anesthesiology and Pain Medicine, UC Davis School of
Medicine; Jason Eiserich, associate professor, Division of Nephrology,
Department of Internal Medicine, UC Davis School of Medicine; and Lukas
Kubala, former UC Davis post-doctoral researcher in Eiserich's lab.
Four UC Davis departments collaborated on the project: entomology,
internal medicine, anesthesiology and pain medicine, and physiology and
membrane biology, along with the UC Davis Cancer Research Center.
The work drew grant support from the National Institute of
Environmental Health Sciences, Superfund Basic Research Program, and
the Center for Children's Environmental Health and Disease Prevention,
as well as a research award from the UC Davis Health Systems to
Eiserich; a Paul F. Gulyassy Endowed Professorship to Eiserich; a UC
Davis Department of Anesthesiology and Pain Medicine award to Jinks and
a National Institute General Medical Sciences grant to Jinks.
The paper is online at http://www.pnas.org/.
==========================================================
Gosh if someone teams these mice lacking LITAF (see below) with
psoriatic mice
we're in business as to nailing the pathway for how LPS works in
inflammatory pathways that deal with psoriasis. Or so I hope.
http://www.eurekalert.org/pub_releases/2006-09/bu-rcm090606.php
Researchers create mouse lacking key inflammation gene
Will likely lead to new treatments for inflammatory disorders
(Boston) -- In a paper published yesterday in The Proceedings of the
National Academy of Science (PNAS), researchers from Boston University
School of Dental Medicine generated a mouse model exhibiting reduced
inflammation.
The Boston University researchers found that the transcription factor
LITAF (Lipopolysaccharide [LPS]-Induced TNF-Alpha Factor) controls
inflammation through a completely different pathway than the better
known and studied NF-kB transcriptional regulator.
Drugs regulating TNF-alpha through the better-known NF-kB pathway such
as Remicade, Embrel, and Humira represent a multibillion market. The
LITAF transcription factor offers a new approach to treating
inflammatory disorders along with other immunological conditions.
Researchers are offering this in vivo model for sale to spearhead
discovery of drugs against inflammatory disorders such as arthritis and
Crohn's disease.
In the study, Boston University researchers created a mouse lacking the
gene that encodes for the LITAF protein. They found that several
cytokines were induced at lower levels in the LITAF-deficient mice
compared with the levels observed in the LITAF-positive control mice.
Specifically, the deficient mice were more resistant to LPS-induced
lethality.
"The generation of the macrophage-specific LITAF-deficient animals
opens new opportunities for assessing the role of LITAF in inflammation
in hopes of designing anti-LITAF drugs for major inflammatory
diseases," says Dr. Salomon Amar of Boston University, the lead author
of the paper. Amar discovered the LITAF transcription factor in 1999.
Researchers, who have applied to patent the mouse, are now working on
whether other molecules work in synergy with LITAF.
###
The paper, "Macrophage-specific LITAF-deficient mice express reduced
LPS-induced cytokine profiling: further evidence for LITAF-dependent
LPS signaling pathways," by Xiaoren Tang, Daniel Metzger, Susan E.
Leeman, and Salomon Amar, may be found here as an abstract
(http://www.pnas.org/cgi/content/abstract/0605988103v1?maxtoshow=&HITS=2&hits=2&RESULTFORMAT=&titleabstract=TNF+or+LPS+or+atherosclerosis&andorexacttitleabs=or&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct)
or pdf
(http://www.pnas.org/cgi/reprint/0605988103v1?maxtoshow=&HITS=2&hits=2&RESULTFORMAT=&titleabstract=TNF+or+LPS+or+atherosclerosis&andorexacttitleabs=or&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct)
------------------------------
This LITAF gene is a big deal for TNF. If you don't respond to p meds
it may be your P pathway.
Do the search of the group.
OK,
http://groups.google.com/groups/search?q=litaf+psoriasis&qt_s=Search
In the p news thread april 3, 2005--- read posts 46 thru 50
================================================
http://www.upi.com/HealthBusiness/view.php?StoryID=20060906-100842-6914r
Anthera licenses Lilly's compounds
SAN FRANCISCO, Sept. 6 (UPI) -- U.S. firm Anthera said Wednesday it
licensed worldwide rights to anti-inflammatory compounds developed by
Eli Lilly and Shionogi.
The terms of the deal were not disclosed, but Anthera said it obtained
worldwide development and commercialization rights, except for in
Japan, to clinical and preclinical inhibitors of phospholipase A2,
which plays a role in inflammation.
"We are excited to have the opportunity to move this novel anti-
inflammatory program forward in a new direction," said Paul Truex,
Anthera's president and chief executive officer. "Recent developments
in the understanding of the biological activity of phospholipases and
inflammation provide the opportunity for a renewed scientific approach
with this program."
Anthera said it plans to initiate clinical studies later this year with
the program's lead compound A-001, which was previously called
LY315920/S-5920, to determine if it can be used for the treatment of
acute chest syndrome in patients with underlying sickle cell disease.
The company said studies indicate there is an increase in
________phospholipase A2_______ levels in patients with this condition.
===============================================
Turning down phospholipase A2 (PLA) reduces AA (arachidonic acid)
production and lowers Psoriasis.
And a sidebar to that,
Others (PLD) help J to metabolize the PC in lecithin.
http://en.wikipedia.org/wiki/Phospholipase
to
http://en.wikipedia.org/wiki/Phosphatidylcholine
I wonder if this Lilly/Anthera (above) compound will help cool
psoriasis?
Will it systemically work to lower arachidonic acid? The fuel for
psoriasis?
Here's an abstract to support that notion.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16712837&query_hl=5&itool=pubmed_docsum
Targeting cytosolic phospholipase A2 by arachidonyl trifluoromethyl
ketone prevents chronic inflammation in mice.
* Malaviya R,
* Ansell J,
* Hall L,
* Fahmy M,
* Argentieri RL,
* Olini GC Jr,
* Pereira DW,
* Sur R,
* Cavender D.
Inflammation Research Team, Department of Drug Discovery, Johnson and
Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ
08869, USA.
Cytosolic phospholipase A(2) (cPLA(2)) plays a pivotal role in
inflammation by catalyzing the release of arachidonic acid, a substrate
for lipoxygenase and cyclooxygenase enzymes, from membrane
phospholipids. In the present study we examined the role of cPLA(2) in
inflammatory responses through the use of a specific inhibitor of the
enzyme, cPLA(2), arachidonyl trifluoromethyl ketone (AACOCF3).
Interestingly, we observed that AACOCF3 is an inhibitor of chronic but
not acute inflammatory responses. Specifically, AACOCF3 inhibited
phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in
mice. Additionally, oral treatment of
ovalbumin-sensitized/ovalbumin-challenged BALB/c mice with 20 mg/kg
AACOCF3 prevented the development of airway hyper-responsiveness in a
model of asthma. Furthermore, AACOCF3 decreased cellular recruitment in
the airway lumen and airway inflammation after the ovalbumin challenge.
Taken together, these results suggest that a potent and specific
chemical inhibitor of cPLA(2) may be useful for the treatment of
chronic inflammatory diseases including rheumatoid arthritis,
inflammatory bowel disease, ___psoriasis___, and asthma.
PMID: 16712837
More abstracts for thoughts about the above,
randall...
randall
One of my main areas of interest has been endotoxins (lps).
So, here we go.
Could one of the reasons people with psoriasis survived the Plague is
because they have psoriasis?
Or? Did they die?
Secrets! ?
http://www.newswise.com/articles/view/523576/
Researchers Uncover a Secret of the Black Death
Newswise - Yersinia pestis, the bacteria that causes plague, is a
sneaky little intruder with a remarkable ability to evade the body's
immune system. Upon entering an organism, Y. pestis employs a variety
of strategies to slip below the radar of the innate immune
response-the body's front line of defense against invading
pathogens-and in many cases kills the host before its more specific
antibacterial response can develop.
[Is autoimmunity the answer to plague?]
It is this stealth and virulence that has made plague one of the most
feared diseases in human history, blamed for more than 200 million
deaths. While human cases of plague in the United States are now rare,
a few thousands worldwide are infected each year and with the potential
of intentional misuse of Y. pestis, the efforts to develop better
treatments and a vaccine are now no less important than they were when
the bacterium was first identified.
Researchers at the University of Massachusetts Medical School have made
a significant breakthrough in the field, modifying Y. pestis with a
gene found in another commonly known bacterium, effectively rendering
it unable to cause plague. In "Virulence factors of Yersinia pestis
are overcome by a strong ___LPS___ response," to be published in the
October issue of Nature Immunology, Egil Lien, PhD, assistant professor
of medicine and molecular genetics & microbiology, Jon D. Goguen, PhD,
associate professor of molecular genetics and microbiology, graduate
student Sara Montminy and colleagues, also describe the effectiveness
of the modified bacteria as a vaccine.
Innate immunity-the precursor to the adaptive immune system in
mammals-acts as the first line of defense against a range of
pathogens. Prior to the adaptive immune response that involves the
body's production of antibodies that precisely target and combat the
invader, the innate immune system reacts immediately upon infection.
Recent research has described an important class of sensor molecules,
collectively known as Toll-like receptors (TLRs) that recognize
pathogens right away, activating the critical signaling pathways that
stimulate this initial immune response. Activation of the TLRs also
improves the adaptive immune response; in fact, many vaccines include
ingredients known as adjuvants that stimulate the innate immune
response.
Intriguingly, the bacteria Y. pestis has an unusual
temperature-dependent ability to evade this system. Lipopolysaccharide,
or LPS, is a major component of the membrane of this type of bacteria,
contributing to structural integrity but also typically provoking a
strong response from the immune system. When at human body temperature
(37ĀŗC), Y. pestis produces an LPS with a poor ability to activate
TLR4, one of the major mammalian innate immunity toll-like receptors;
at lower temperatures, for example that of a flea that transmits the
disease (26Āŗ), the LPS produced was distinctly more potent and thus
triggered TLR4.
[so? is it group B strep LPS for psoriasis?]
Recognizing that this difference was not found in E. coli, a common
bacterium with some similarities to Y. pestis, Lien identified an E.
coli gene that was important for the production of LPS but that was
missing in Y. pestis. Using this gene to generate new strains of Y.
pestis, researchers produced Y. pestis strains that were recognized
much more easily by innate immunity and TLR4 at both temperatures.
Importantly, the investigators found that the new strains were unable
to cause plague and mortality in normal mice; the strains were at least
a million times less virulent than the wild type bacteria.
"Our findings describe one of the secrets of the Black Death," Lien
said. "These results suggest that the production of surface lipids
with poor ability to activate innate immunity is essential for Y.
pestis to be so deadly, and, in fact, for the ability of the bacteria
to cause plague. We expect this strategy to also be important for
various other human bacterial pathogens."
"This result is quite surprising, in part because plague research has
focused on many active things that the bacteria do to protect
themselves from host defenses, including injecting toxins directly into
cells of the immune system that try to engulf them," notes Goguen.
"Apparently all of this is useless unless the bugs can also hide from
TLR4. Stealth is important."
Significantly, Lien and colleagues also determined that these new
harmless strains of Y. pestis could serve as vaccines. After
vaccinating mice with the modified strain of Y. pestis, the
investigators re-introduced the virulent strain after 30 days and found
that all of the animals were protected from developing plague. These
findings show that the production of avirulent bacterial strains with
enhanced ability to stimulate the immune system could constitute a new
general method for generating effective vaccines.
The University of Massachusetts Medical School, one of the fastest
growing academic health centers in the country, has built a reputation
as a world-class research institution, consistently producing
noteworthy advances in clinical and basic research. The Medical School
attracts more than $174 million in research funding annually, 80
percent of which comes from federal funding sources. UMMS is the
academic partner of UMass Memorial Health Care, the largest health care
provider in Central Massachusetts. For more information visit
http://www.umassmed.edu.
------------------------------
The LPS connection to p and heart disease?
http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/tb/4118
SACRAMENTO, Calif., Sept. 15 -- Statin therapy may have an
anti-inflammatory benefit for patients with metabolic syndrome:
researchers here reported.
The metabolic syndrome, which includes abdominal obesity and
hypertension, is also characterized by low-grade inflammation,
increasing the risk for cardiovascular disease and diabetes, said
Ishwarlal Jialal, M.D., Ph.D., of the University of California Davis
here and colleagues.
In a double-blind, randomized, placebo-controlled study, statin therapy
reduced two biomarkers of inflammation-C-reactive protein (CRP) and
interleukin-6 (IL6)-according to a study reported in the Sept. 12 issue
of the Journal of Clinical Endocrinology and Metabolism.
Previously Dr. Jialal's group had held that statins, as a class of
drugs, are anti-inflammatory. Numerous studies have shown that statins
lower biomarkers of inflammation in patients with coronary artery
disease, diabetes, and hypercholesterolemia, he said. However, he
added, there is a "paucity of data" in individuals with the metabolic
syndrome.
To study the direct effect of the drugs on biomarkers of inflammation
in the circulation but also on monocytes, cells pivotal in plaque
formation, the researchers gave 50 metabolic syndrome patients a
standard dose of simvastatin (40 mg/day). Controls received a placebo.
After eight weeks, as expected, they found that statin therapy produced
a significant reduction in total cholesterol (25%), LDL cholesterol
(32%), and non-high-density lipoprotein levels (42%), compared with
baseline and placebo. Triglycerides and high-density lipoprotein
cholesterol were unchanged.
Dr. Jialal and his team also found marked reductions in the two pivotal
biomarkers of inflammation. Although these markers are usually elevated
in insulin resistance, simvastatin therapy had marked effects as shown
by a 36% decrease in levels of hsCRP (P<0.005) compared with baseline
and placebo, and a 44% decrease in plasma IL-6 (< 0.025), a molecule,
along with tumor necrosis factor (TNF), involved in insulin resistance
and cardiovascular disease.
To study the way statins work at the molecular levels, human monocytes
were pretreated with lovastatin with and without various inhibitors.
Monocytes are pivotal inflammatory cells in all stages of atherogenesis
and secrete pro-inflammatory cytokines such as the interleukins and
TNF, which in turn promote CRP synthesis, the researchers wrote.
_____Lipopolysaccharide-activated____ monocytic release of both IL-6
and tumor necrosis factor (TNF) were significantly decreased after
simvastatin treatment compared with baseline and placebo (P<0.05 and
P<0.01 respectively).These two molecules are critical in causing
insulin resistance and the development of cardiovascular disease, the
researchers said.
Lovastatin also significantly decreased Rho kinase and NFkB activity
and significantly increased Akt activity in metabolic syndrome
patients, compared with baseline and placebo, they reported.
In addition, the researchers also found that simvastatin inhibited a
protein (NF kappa B) that serves as a "master switch" in the
inflammatory process. "We also demonstrated increased production of a
key enzyme (PI3-kinase) related to insulin activity," said Sridevi
Devaraj, Ph.D., a study coauthor.
Thus, Dr. Jialal said, "we demonstrate for the first time in subjects
with metabolic syndrome that simvastatin results in significant
reduction in inflammation, as shown by these changes." This, coupled
with the in vitro observations of decreased Rho activity by lovastatin,
provide direct evidence for the anti-inflammatory effects of statin
therapy via protein effects on monocytes, he added.
Changes in diet and exercise are still the treatment of choice for
preventing the consequences of metabolic syndrome, Dr. Jialal said,
"However, people don't always adhere to those changes," he concluded.
"Our results suggest that statin may be a way to forestall the deadly
complications of the metabolic syndrome."
Future studies, Dr. Jialal wrote, will examine the role of statin
therapy in directly reducing adipose tissue biology with respect to
inflammation. "We also need long-term studies that look at the effects
of statins on insulin resistance and diabetes prevention," he said.
The researchers wrote that this study was supported in part by a Merck
Medical School grant.
----------------------
randall...
randall
One way to look at psoriasis is to look at similar immune mediated
inflammatory disorders (I.M.I.Ds). And there has been
a bunch of hits for MS recently. So? What's the buzz?
Well, for one thing P and MS are both Th1 skewed I.M.I.Ds and
may share more then a few things in pathways that are still
unknown.
Here's a gene article for MS that caught my attention.
http://www.theherald.co.uk/news/70998.html
'Angel and devil' genes hold the key to treatment for MS
Multiple Sclerosis symptoms can be affected by a pair of "angel and
devil" genes that fight to make a patient healthy or ill, researchers
have found.
The discovery could help scientists find ways of tackling the
potentially devastating disease.
Scotland has the highest proportion of MS sufferers in the world -
about 10,500 have the condition.
One of the genes thought to be responsible for MS is called DR2b.
Now scientists have learned that it is the "evil twin" in a pair of DR2
genes.
MS is a life-long condition with symptoms including
pain, muscle problems, impaired mental function, and poor vision. In
severe cases it can lead to disabling loss of limb movement.
MS symptoms are caused by a rogue immune response, where the body
attacks its own central nervous system.
The researchers found that DR2b exacerbates these symptoms, but its
partner gene DR2a tries to dampen them and counteract DR2b's effects.
Professor Lars Fugger, from the Medical Research Council's Human
Immunology Unit at Oxford University, who led the study, said: "The
DR2b gene clearly tells the immune system to go hard into battle
against the body's own tissue, so it starts to work in a way that
actually damages the person.
"For this reason, natural selection has eliminated the gene on its own,
but allowed it to be inherited only when it is accompanied by another
gene (DR2a) which tempers its effect."
Professor Fugger's team bred mice with different combinations of DR2
genes in order to investigate their effects.
(whoops- sorry!)
gene clearly tells the immune system to go hard into battle against the
body's own tissue, so it starts to work in a way that actually damages
the person.
"For this reason, natural selection has eliminated the gene on its own,
but allowed it to be inherited only when it is accompanied by another
gene (DR2a) which tempers its effect."
Professor Fugger's team bred mice with different combinations of DR2
genes in order to investigate their effects.
The scientists, whose findings appear today in the journal Nature, hope
exploiting DR2a's control mechanism may lead to treatments for MS.
Research into other autoimmune diseases may benefit. Professor Fugger
said: "This study is not only relevant to understand how genes interact
in MS, but also in diabetes, rheumatoid arthritis and ___psoriasis___,
which are all autoimmune diseases."
Simon Gillespie, chief executive of the Multiple Sclerosis Society,
said: "This is a very interesting finding which adds another piece to
our understanding of the MS puzzle . . . We share the researchers' hope
that it could eventually play a part in helping to treat this very
variable and unpredictable condition."
(randall note:: autoimmune and I.M.I.Ds are the same thing)
http://en.wikipedia.org/wiki/IMID
-------------------
And finding a current abstract for this gene and MS.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16111772&query_hl=17&itool=pubmed_docsum
HLA-DRB5*0101 and -DRB1*1501 expression in the multiple
sclerosis-associated HLA-DR15 haplotype.
Neuroimmunology Branch, National Institute of Neurological Disorders
and Stroke, National Institutes of Health, Building 10, Room 5B16, 10
Center DR, Bethesda, MD 20892-1400, USA.
The HLA region, and particularly the DR15 haplotype (containing the two
DRB* genes DRB1*1501 and DRB5*0101 and the tightly linked DQ alleles
DQA*0102 and DQB1*0602, which together form the DQw6 molecule) in
Caucasians, shows the strongest genetic association with multiple
sclerosis (MS). In the DR15 haplotype, two beta-chains HLA-DRB1*1501
and -DRB5*0101 are co-expressed resulting in two different surface
HLA-DR alphabeta heterodimers, DR2b and DR2a. Most previous studies
focused on DRB1*1501, however, both DR2a and DR2b may contribute to MS
pathogenesis via antigen presentation to myelin-specific T lymphocytes.
We therefore analyzed the expression of the two DR15 genes in various
antigen presenting cells (APCs), central nervous system and thymic
tissues. Transcript levels were higher for DRB5*0101 in all cell types
and tissues. Both ___HLA-DR__ heterodimers were expressed at
significant levels on the cell surface, where they showed a
differential expression pattern in different APCs. They were similarly
regulated after stimulation with interferon-gamma and interleukin-4.
Finally, immunohistochemistry experiments indicated that both molecules
were expressed in thymic tissue. Our results encourage future research
to investigate the potential functional relevance of both genes for the
pathogenesis of MS.
PMID: 16111772
Coincidentally we have a vitamin supplement for MS showing up recently.
http://www.newscientist.com/article/dn10130?DCMP=NLC-nletter&nsref=dn10130
Vitamin hope for multiple-sclerosis treatment
A simple vitamin has dramatically reduced neurological damage in mice
suffering from a multiple sclerosis-like illness, a new study reveals.
As a result, the researchers hope that a form of vitamin B3
(____nicotinamide___), may help reduce long-term disability in people
with multiple sclerosis.
MS is caused by the body's immune system attacking the protective
myelin sheath that coats nerve cells. Without this white, fatty
material, electrical signals passing to and from the brain are
disrupted, and sufferers become increasingly physically disabled. There
is currently no cure.
Current drugs aim to reduce destruction of myelin by suppressing
patients' immune systems. However, this has a side effect of making
them more prone to infection. And these drugs do nothing to conserve
remaining nerves - even if they lack myelin - once the disease has
progressed.
Late-stage help
In the new research, Shinjiro Kaneko at the Children's Hospital
Boston in Massachusetts, US, and colleagues gave a daily dose of
nicotinamide to mice that had an MS-type disease, called experimental
autoimmune encephalopathy (EAE).
The vitamin protected the mice from further myelin damage and improved
the function of nerve cells that had lost myelin, suggesting that it
could help people in late-stage MS. The more nicotinamide they gave the
mice, the greater the protective effect, the team found.
Mice receiving daily injections of nicotinamide only showed slightly
reduced mobility, such as the dragging of a hind leg. In contrast, mice
in the no-treatment group had severe hind-limb weakness or paralysis.
Sight saving
"That's an enormous difference," says Peter Werner at the Albert
Einstein Collage of Medicine in New York, US, who was not involved with
the study. "It is the difference, for example, between a mouse that
can reach its food and one that can't."
"It's highly desirable to hang on to functioning nerves as long as
possible, even if they're naked because they have no myelin,"
Werner told New Scientist. He adds that doing so could potentially
delay loss of mobility or sight in a patient with MS.
When nerves lose myelin they have to work harder to send signals, and
this stress appears to damage them further, Werner explains.
Widely available
Kaneko believes that nicotinamide worked in the mice because it raises
the level of a key nervous system chemical called nicotinamide adenine
dinucleotide (NAD), which appears to improve the energy efficiency of
nerve cells. And NAD may also inactivate the immune cells that attack
myelin, Kaneko suggests.
Nicotinamide is widely available in health food stores and pharmacies
as a form of vitamin B3. The proven safety and availability of the
compound make it an appealing candidate to treat MS, experts say,
particularly since the chemical is small enough to cross the
blood-brain barrier.
And unlike current multiple sclerosis (MS) drugs, nicotinamide does not
appear to have unpleasant side effects.
However, Kenneth Maiese at Wayne State University School of Medicine in
Detroit, Michigan, US, points out that the doses given to the mice in
the study were quite high. Similar doses in humans may prove toxic, he
cautions.
For this reason, experts stress that MS patients should not take
vitamin B3 for their illness until clinical trials show that it has an
effect in humans.
Journal reference: Journal of Neuroscience (DOI:
10.1523/jneurosci.2116-06.2006)
--------------------------------------
Now let's look at HLA-DR and psoriasis (there are no hits for DR2A or
we'd have MS instead of P)
And then look at HLA-DR and HLA-DR2A,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20hla-dr+hla-dr2a
Looking at the first two hits we find StreP and zinc fingers
overlapping with both P and MS conditions.
I know i've seen zinc finger (mine/others) posts in our group,
http://groups.google.com/groups/search?q=zinc+fingers+psoriasis&qt_s=Search
And the first hit has zinc finger implications but more importantly
nicotinamide usage to
cause a Th2 bias. Anything that slows the Th1 skew of psoriasis or MS
would be
a GOOD thing.
And a Nicotinamide search of our group turns up it's usage for diabetes
as well.
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=nicotinamide
But not in this trial,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15043959&dopt=Citation
These I.M.I.Ds (p, ms and diabetes) are showing a pattern or giving up
a few secrets.
randall... To B3 or not to B3! ... HoW CLEAR isn't Clear yet!
randall
Special P News that may or not be involved in the clearing of P.
New use for Turmeric. Skin whitening, could it be useful?
http://www.medicalnewstoday.com/medicalnews.php?newsid=53821&nfid=nl
Naris Cosmetics Co., Ltd. has announced its recent discovery that skin
whitening power made with turmeric is four times as strong as that made
with the conventional arbutin.
The company conducted two clinical trials using cultured cells to find
out how effective turmeric is in reducing melanin on suntanned human
skin.
According to the trials, turmeric applied to cultured melanocytes was
found to cut melanin-producing receptor modules by 60%. A test using
cultured human skin cells was found to reduce melanin production by
40%. Another test using skin tonic with turmeric resulted in faster
recovery of suntanned skin.
Naris has already filed a patent application and will announce its
findings at a meeting of the International Federation of Societies of
Cosmetic Chemists (IFSCC), being held from October 16-19 in Osaka.
----------------------------
Gi tract toxin found!
http://www.medicalnewstoday.com/medicalnews.php?newsid=53741&nfid=nl
Mayo Clinic researchers have uncovered a new link between celiac
disease, a digestive condition triggered by consumption of gluten, and
dementia or other forms of cognitive decline. The investigators' case
series analysis -- an examination of medical histories of a group of
patients with a common problem -- of 13 patients will be published in
the October issue of Archives of Neurology.
"There has been very little known about this connection between celiac
disease and cognitive decline until now," says Keith Josephs, M.D.,
Mayo Clinic neurologist and study investigator. "This is the largest
case series to date of patients demonstrating cognitive decline within
two years of the onset of celiac disease symptom onset or worsening."
Says Joseph Murray, M.D., Mayo Clinic gastroenterologist and study
investigator, "There has been a fair amount written before about celiac
disease and neurological issues like peripheral neuropathy (nerve
problems causing numbness or pain) or balance problems, but this degree
of brain problem -- the cognitive decline we've found here -- has not
been recognized before. I was not expecting there would be so many
celiac disease patients with cognitive decline."
The next step in the research will be to investigate the measure and
nature of the connection between the two conditions.
"It's possible it's a chance connection, but given the temporal link
between the celiac symptoms starting or worsening and the cognitive
decline within a two-year time span, especially the simultaneous
occurrence in five patients, this is unlikely a chance connection,"
says Dr. Josephs. "Also, these patients are relatively young to have
dementia."
Theories to explain the connection between celiac disease and cognitive
decline include the following, according to Dr. Murray:
* Nutritional deficiency
* Inflammatory cytokines -- chemical messengers of inflammation that
could contribute to problems in the brain
* An immune attack on the brain that may occur in some patients with
celiac disease
The cognitive decline that occurred in three of the celiac disease
patients studied, according to Dr. Josephs, is relatively unique in its
reversal in two of the patients and stabilization in one patient.
Typically, cognitive decline continues to worsen, he says. "This is key
that we may have discovered a reversible form of cognitive impairment,"
he says.
William Hu, M.D., Ph.D., Mayo Clinic neurology resident and study
investigator, says that the reversal or stabilization of the cognitive
symptoms in some patients when they underwent gluten withdrawal also
argues against chance as an explanation of the link between celiac
disease and cognitive decline.
Currently, the investigators do not know which celiac disease patients
are at risk for cognitive decline; this deserves future investigation,
says Dr. Hu.
Dr. Murray suggests that recognizing and treating celiac disease early
will likely prevent most consequences of the disease, including
symptoms in the gut or the brain. For celiac disease patients who have
already developed cognitive decline, closely following a gluten-free
diet may result in some symptom improvement, he says. For those with
cognitive decline without a confirmed diagnosis of celiac disease, he
does not recommend a gluten-free diet, however.
Physicians can play an important role in keeping alert to a potential
celiac disease and cognitive decline connection, says Dr. Hu.
"For patients who come in with atypical forms of dementia, we need to
consider checking for celiac disease, especially if the patients have
diarrhea, weight loss or a younger age of onset -- under age 70," he
says.
To conduct this case series analysis, the researchers identified 13
Mayo Clinic patients with documented cognitive impairment within two
years of onset of symptoms or severe exacerbation of adult celiac
disease. All celiac disease had been confirmed by small-bowel biopsy,
and any patients for whom an alternate cause of cognitive decline could
be identified were excluded from the analysis. Patients included five
women and eight men, with a median onset of cognitive decline at age 64
that coincided with onset or worsening of symptoms of diarrhea, the
presence of excess fat in the stools and abdominal cramping in five
patients. The most common reasons for seeking medical help were
amnesia, confusion and personality changes. The average score on the
Short Test of Mental Status among the 13 patients was 28 out of 38
possible total, indicating moderate cognitive impairment. Ten patients
experienced loss of coordination and four experienced symptoms of
peripheral neuropathy. Four patients demonstrated deficiency in folate,
vitamin B-12, vitamin E or a combination of these deficiencies,
although supplementation did not improve the patients' cognitive
decline. Three patients' cognitive decline either improved or
stabilized when they completely withdrew from gluten consumption. A
brain autopsy or biopsy was completed in five patients, and there was
no evidence of Alzheimer's disease or any other well-known causes for
dementia.
Celiac disease occurs in 1 out of 133 people and predominantly affects
Caucasians, according to Dr. Murray. Symptoms can include intermittent
diarrhea, abdominal pain and bloating, or no gastrointestinal symptoms
at all. It can also manifest in weight loss, fatigue, anemia, general
weakness, foul-smelling or grayish stools that may be fatty or oily,
osteoporosis or stunted growth (in children only). The condition may
also cause symptoms far outside of the gut. Nine out of 10 times, the
disease is not discovered due to the vague nature of the symptoms,
according to Dr. Murray. The treatment for celiac disease is a
gluten-free diet. For further information on celiac disease,
see http://www.mayoclinic.com/health/celiac-disease/DS00319
--------------------------------------------------
IRF6 wound healing gene,
http://www.medicalnewstoday.com/medicalnews.php?newsid=54227&nfid=nl
[...]
Skin is an extremely important tissue, as it is the largest tissue in
the body and it provides a critical external barrier. Normal epidermis
has four layers of keratinocytes. The UI study showed that mice that
lack IRF6 have abnormal skin development and are missing the upper two
cellular layers of the epidermis. The researchers also showed abnormal
proliferation of keratinocytes in one of the remaining two layers and
failure of these cells to die off or differentiate as normal.
Although humans with Van der Woude syndrome do not have skin defects, a
similar human condition, called popliteal ptyergium syndrome (PPS) that
is also caused by mutations in IRF6, does cause skin abnormalities in
addition to cleft lip and palate. Thus, the UI researchers were not
completely surprised by the skin abnormalities in the mice. <sniP>
-----------------------------------
http://news.biocompare.com/newsstory.asp?id=155268
Friendly Bacteria In Alcoholic Milkshake Could Fight Food Allergies
10/15/2006
Source: Society of Chemical Industry
Feeding babies alcoholic milk may help to protect against some food
allergies. Kefir, a traditional fermented drink, is consumed in Eastern
Europe as a health food, and is often used to wean babies, as it is
easily digested. Food allergy prevalence is especially high in children
under the age of three, with around 5-8% of infants at risk. Currently
the only treatment is avoidance of the problematic food.
"Friendly" bacteria in kefir may play a role in blocking the pathway
involved in allergic responses, Lisa Richards reports in Chemistry &
Industry, SCI's fortnightly magazine. Research published today [Monday
16 October 2006(DOI 10.1002/jsfa2469)] in the SCI's Journal of the
Science of Food and Agriculture has shown that the milk drink inhibits
the allergen specific antibody Immunoglobulin E (IgE). IgE is involved
in immune responses to inactivate organisms that might cause disease.
However, in the presence of allergens it can also activate cells
responsible for the release of histamine, a chemical which stimulates
allergic responses, such as inflammation and constriction of airways.
Ji-Ruei Liu's team of scientists at the National Formosa University,
Yunlin, Taiwan, fed mice the milky drink, and found that after 3 weeks,
the amount of ovalbumin (OVA) specific IgE was reduced three-fold.
Ovalbumin is an allergenic protein found in egg whites, which cause
most allergies in young children. Kefir is also reported to prevent
food antigens from passing through the intestinal wall.
Liu believes that the milky drink could be a promising tool in the
prevention of allergies. "In the future, maybe we can screen out the
certain components (bacterial strains or bioactive peptides) from kefir
and utilize them in medicine," he said.
Also in this weeks Chemistry & Industry, UK firm Rigest are looking for
backers to develop an air sanitizing system using an enzyme found
naturally in human tears. Lactoperoxidase can attack and kill microbes
such as 'flu viruses and the bacteria responsible for MRSA. The system
could be used to sanitize the air in airplanes and hospital sick bays.
------------------------------------
http://news.biocompare.com/newsstory.asp?id=154579
LIAI Scientists Make Major Advance In The Fight Against Chronic Virus
Infections
10/9/2006
Source: La Jolla Institute for Allergy and Immunology
Research could lead to new treatments for hepatitis C and other chronic
infections
A major finding that could lead to a new approach for treating
hepatitis C and other chronic virus infections was announced today by
researchers at the La Jolla Institute for Allergy & Immunology (LIAI).
The research team, using controlled laboratory studies of mice, was
able to eliminate a chronic virus infection in the animals by blocking
a key messenger molecule in the immune system. The finding has
particular relevance for hepatitis C, a viral illness which can cause
liver disease and cancer, but may also be applicable to AIDS,
cytomegalovirus and other chronic virus infections.
"This is a significant advance that holds great promise for the
treatment of chronic virus infections," said Mitchell Kronenberg, LIAI
President & Scientific Director. He noted that the research is
particularly exciting because the scientific team was able to
completely eradicate the usually chronic infection in the mice, not
just tone it down, like many of the current treatment methods for such
infections.
The research team, led by Matthias von Herrath, M.D., announced its
finding in a paper, "Resolution of a Chronic Viral Infection Following
IL-10 Receptor Blockade," published today in the online version of the
Journal of Experimental Medicine. A separate study, led by Michael
Oldstone from the Scripps Research Institute, produced similar results
and was published Sunday in a science journal. <sniP>
--------------------------------------
http://news.biocompare.com/newsstory.asp?id=155271
New Engineered Drug May Offer Prolonged Arthritis Relief
10/15/2006
Source: Duke University
Researchers at Duke University have devised a new way to significantly
prolong the effects of an anti-inflammatory drug, potentially making it
useful for providing longer-lasting treatment for osteoarthritis, the
most common form of arthritis.
The modified drug, which would be injected directly into arthritic
joints, could last for several weeks rather than just the few hours the
unmodified drug would last, the researchers said.
In their study, the researchers modified a drug called interleukin-1
receptor antagonist (IL1RA). They found that the drug, which is a
protein, could be improved by attaching a second protein that clumps
together at normal body temperatures. The combined drug likewise would
assemble into clumps in the body to serve as "drug depots" that
gradually release active drug particles, the researchers said.
"Although the conventional drug is being used for autoimmune diseases,
no one yet knows how much of it would be needed to achieve a
therapeutic effect for osteoarthritis," said Lori Setton, associate
professor of biomedical engineering and surgery. "Current estimates
suggest it would require perhaps two injections per week of the
unmodified drug.
"With this advance, we believe treatments could go from twice a week to
perhaps twice a month, and that would be a huge clinical gain," she
said.
<sniP>
--------------------------
Here's a wow story.
http://www.medicalnewstoday.com/medicalnews.php?newsid=54061&nfid=nl
Major Biofilm Dispersion Breakthrough By Binghamton University
Researcher
Main Category: Biology / Biochemistry News
Article Date: 16 Oct 2006 - 18:00pm (PDT)
* Infectious Diseases / Bacteria / Viruses
A Binghamton University biologist's discovery of a molecule that
induces the dispersion of biofilms will likely mean a sea change in
health care, manufacturing, shipping and pharmaceutics over the coming
years.
David Davies has found and is in the process of synthesizing a compound
that will cause biofilm colonies to disperse, thus leaving individual
bacteria up to 1,000 times more susceptible to disinfectants,
antibiotics and immune functions. It's a discovery that will most
certainly drive worldwide biofilm research in new directions and that
could help put some of the most virulent cells in all of nature out of
business.
Biofilms are complex aggregations of bacteria marked by the excretion
of a protective and adhesive matrix. They develop almost anywhere that
water and solids, or solids and gases meet, which means they are
virtually everywhere. They are formed when individual microorganisms
embed themselves in a gelatinous structure of their own making. When
traveling alone in planktonic form, most bacteria are of small
consequence and generally easy to manage, even with antibacterial hand
soaps. But when they form biofilms, bacteria seem to gain super powers.
In human terms the characteristic "slime" of biofilms, which comprises
organic polymers that can grow to several centimeters thick and cover
large areas, spells all kinds of big trouble.
<sniP>
---------------------------------------
Cheaper ethanol and booze! (That would make some psoriatics haPPY!)
http://www.medicalnewstoday.com/medicalnews.php?newsid=53805&nfid=nl
Cyanobacteria (blue green algae)
http://www.medicalnewstoday.com/medicalnews.php?newsid=53802&nfid=nl
--------------------------------------
Cox-2 secrets could help us!
http://www.medicalnewstoday.com/medicalnews.php?newsid=53661&nfid=nl
Blood Cells Linked To Heart Attacks, Stroke And Other Inflammatory
Diseases
Main Category: Blood / Hematology News
Article Date: 10 Oct 2006 - 8:00am (PDT)
Two human blood cells that help fight blood loss, infection, and
inflammation are responsible as well for starting a series of molecular
events that results in overproduction of Cox-2, an enzyme involved in
heart attack, stroke, atherosclerosis, and other inflammatory diseases.
The finding by researchers at the University of Utah and University of
South Carolina means scientists may be able to develop drugs to prevent
or lessen the severity of inflammatory diseases, such as
atherosclerosis and heart attack. Discovery of the signaling mechanism
will be invaluable in sorting out the roles Cox-2 plays in those
diseases, according to Guy A. Zimmerman, M.D., University of Utah
School of Medicine professor of internal medicine, senior author of the
study detailing the research.
"This discovery has immediate clinical relevance," said Zimmerman,
director of the medical school's Program in Human Molecular Biology and
Genetics. "This opens the potential of developing medications for both
the prevention of long-term atherosclerosis (clogged arteries) and the
acute events of heart attack."
v The study, reported in the Journal of Clinical Investigation online,
also was led by Dan A. Dixon, a former member of Zimmerman's lab now at
South Carolina.
The researchers identified a biochemical signaling pathway between
human blood platelets, cells essential for blood clotting, and
monocytes, white blood cells the body makes to fight inflammation and
infection. But, according to Zimmerman, the biological systems involved
in blood clotting and inflammation also are related to a host of human
diseases.
The Utah and South Carolina researchers discovered that the blood
platelet signals the monocyte two times, triggering production of
Cox-2, an enzyme that helps regulate inflammation. But when blood
platelets and monocytes get their signals crossed, it can lead to
overproduction of the enzyme and result in cardiovascular diseases that
strike and kill millions of people worldwide.
Zimmerman compares the signaling between blood platelets and monocytes
to a pair of molecular control switches that turn Cox-2 production on
and off. "It's a mechanism for precise control of Cox-2 production," he
said. "But if one of the switches is turned on too high or low, it can
lead to inappropriate production of Cox-2 in disease."
The first signal from the platelet tells the monocyte to turn on the
gene that provides the instructions necessary to make Cox-2. These
instructions are carried in small molecule called messenger RNA. When
the blood platelet signals the monocyte, the cell decodes the
instructions from the Cox-2 gene in a process called transcription.
This results in production of messenger RNA that specifically codes for
Cox-2. After the messenger RNA is transcribed, the blood platelet then
sends a second signal to the monocyte that regulates stability of the
Cox-2 messenger RNA and further decoding of the genetic information in
a process called translation.
This results in production of the Cox-2 protein and controls how much,
and at what time point, it is produced.
Drugs called non-steroidal anti-inflammatory agents, which inhibit
production of Cox-2 and reduce inflammation, are some of the most
widely used medications in the world for arthritis and other
inflammatory diseases. But some of these drugs, also called Cox-2
inhibitors, such as Vioxx, increase the chance of heart attack.
Identifying the signaling mechanism between blood platelets and
monocytes makes it possible to develop new drugs to modify Cox-2
production. "Knowing these steps gives you an initial blueprint about
how to modify Cox-2," Zimmerman said. Understanding this mechanism may
enable researchers to develop drugs that help people during a heart
attack, or prevent heart attack, stroke or other inflammatory diseases
---------------------------------------------
EAt some walnuts with fatty meals to protect arteries,
http://www.medicalnewstoday.com/medicalnews.php?newsid=53890&nfid=nl
SuPer allicin garlic,
http://www.medicalnewstoday.com/medicalnews.php?newsid=53660&nfid=nl
Cut out the omega-6's and in particular if you have the GENE!
http://www.medicalnewstoday.com/medicalnews.php?newsid=53574&nfid=nl
Researchers from the Jean Mayer USDA Human Nutrition Research Center
(USDA HNRCA) at Tufts University and colleagues have found another link
among genes, heart disease and diet. The study, published in
Circulation, examined apolipoprotein A5 (APOA5), a gene that codes for
a protein, which in turn plays a role in the metabolism of fats in the
blood. The results show that people who carry a particular variant of
APOA5 may have elevated risk factors that are associated with heart
disease, but only if they also consumed high amounts of omega-6 fatty
acids in their diets.
Corresponding author Chao-Qiang Lai, PhD, a USDA-Agricultural Research
Service (ARS) scientist at the USDA HNRCA, and colleagues analyzed
lipid levels and dietary assessment questionnaires of more than 2,000
participants in the Framingham Heart Study and quantified their intake
of different types of fats.
Omega-6 fatty acids, as well as omega-3 fatty acids, are
polyunsaturated fatty acids (PUFAs) and, according to a report from the
National Institutes of Health Office of Dietary Supplements, most
Americans consume about 10 times more omega-6s than omega-3s. Omega-3s
are found in nuts, leafy green vegetables, fatty fish, and vegetable
oils like canola and flaxseed, while omega-6s are found in grains,
meats, vegetable oils like corn and soy, and also processed foods made
with these oils. Both omega-3s and omega-6s, known as essential fatty
acids, must be consumed in the diet because they are not made by the
body.
"We know that some people are genetically predisposed to risk factors
for heart disease, such as elevated low-density lipoprotein levels in
the blood," says Lai, "and that APOA5 has an important role in
lipoprotein metabolism. We wanted to determine if certain dietary
factors change the role of APOA5 in metabolizing these lipoproteins and
their components, such as triglycerides."
Lai and colleagues found that approximately 13 percent of both men and
women in the study were carriers of the gene variant. Those individuals
that consumed more than six percent of daily calories from omega-6
fatty acids displayed a blood lipid profile more prone to
atherosclerosis (hardening of the arteries) and heart disease,
including higher triglyceride levels.
Jose Ordovas, PhD, senior author of the study and director of the
Nutrition and Genomics Laboratory at the USDA HNRCA, notes that
"previous research points to polyunsaturated fatty acids like omega-3s
and omega-6s as 'good' fats, thought to reduce risk of heart disease by
lowering cholesterol levels if used in place of saturated fats that are
mostly found in animal sources."
Ordovas continues, "Research hasn't shown us yet if there is an optimal
ratio for omega- 3s to omega-6s, or if consuming a certain amount of
omega-6s might negate the benefits of omega-3s. We do know that
omega-6s are necessary for the body and can be a source of healthful
fat in the diet, but for the 13 percent who are carriers of the
particular APOA5 gene variant, consuming fewer omega-6s in relation to
omega-3s may be important, as it might help reduce the risk of
developing precursors to heart disease."
The carriers of the variant who ate more than six percent of total
calories from omega-6s had a 21 percent increase in triglyceride
levels, as well as an approximately 34 percent elevation of certain
atherogenic lipoprotein particles in the blood.
Carriers who consumed less than six percent of total calories from
omega-6s did not show a significant increase in the lipid levels that
are risk factors for heart disease. In contrast to omega-6s, higher
consumption of omega-3s decreased triglyceride and atherogenic
lipoprotein particle levels in the blood, regardless of a person's
APOA5 gene variant.
Although the researchers analyzed information on several types of
dietary fat, including saturated fat and monounsaturated fat, the
interactions between diet and APOA5 were seen only with PUFAs, "adding
evidence to the prominent role of PUFAs as modulators of genetic
effects in lipid metabolism," write the authors. They go on to explain
that "a more complete understanding of these factors and a thoughtful
use of this information should help in the identification of vulnerable
populations who will benefit from more personalized dietary
recommendations."
A second study published by Ordovas, Lai, and colleagues in the Journal
of Lipid Research also studied variants of the APOA5 gene in
participants in the Framingham Heart Study to determine if the gene is
related to atherosclerosis. The authors, including corresponding author
Christopher O'Donnell of the National Heart, Lung, and Blood
Institute's Framingham Heart Study, and first author Roberto Elosua, a
former Fulbright-Generalitat de Catalu a fellow who works with Ordovas,
found that while most variants of the APOA5 gene were not associated
with carotid intimal medial thickness (IMT), a surrogate measure of
atherosclerosis burden, particular gene variants were "significantly
associated with carotid IMT in obese participants."
Carriers of the particular gene variants who were obese expressed the
effects of the gene variant differently than carriers who were not
obese, showing a greater build-up of plaque in the heart. This was true
for participants who were obese regardless of fat and cholesterol
levels in the blood, age, gender, smoking or diabetes status,
weight-for-height and blood pressure, all factors which are thought to
influence risk of heart disease. Lai notes that "although obesity is a
known contributing factor to heart disease, the association was
strengthened in carriers of the rare APOA5 variant who were obese."
"It may be more important for some people to make preventive dietary
and lifestyle changes than others, depending on their genetic makeup,"
says Ordovas. "The 'bad' genotype, in this study, doesn't seem to be
that bad unless it's triggered by obesity," he concludes. "The
observations, while strong, should be considered with caution and
confirmed in other studies. Also, the findings were restricted to a
Caucasian cohort and may not be generalizable to other ethnic cohorts."
--------------------------------------------------------------------
randall
randall
Areas that may help to cure P in the future.
http://news.biocompare.com/newsstory.asp?id=155757
Potential New Therapeutic Target For Asthma, Allergies And Cancer
10/17/2006
Source: Virginia Commonwealth University
Transport mechanism of bioactive molecule, S1P, identified
Virginia Commonwealth University researchers have identified how a
bioactive molecule involved with allergy, inflammation and cancer is
transported out of mast cells, according to findings published online
this week in the Proceedings of the National Academy of Sciences.
Mast cells are specialized cells that react to allergy-causing agents
by releasing substances that trigger the body's allergic response,
leading to conditions like asthma and hives. Among the molecules
released by mast cells that participate in the allergic response is
sphingosine-1-phosphate. This molecule is also implicated in cancer.
The work by the VCU investigators opens up a new approach to treating
asthma, which affects about 15 million Americans and is increasing in
incidence and mortality, especially among African-Americans. It also
has implications for other allergic disorders and for cancer in terms
of developing drugs that inhibit the transport of SIP out of cells.
Sarah Spiegel, Ph.D., professor and chair, VCU Department of
Biochemistry, and colleagues reported how S1P, which also regulates
many important physiological functions in cells, is transported out of
mast cells. S1P is produced by all cells and secreted by some cells
into the circulation where it can bind to specific S1P receptors. Until
now, researchers have not known the mechanism by which S1P is
transported out of cells.
"Our study shows that mast cells can use a special kind of transporter
that has long been known to be used by cancer cells to push anti-cancer
drugs out and help them survive the treatment," said Spiegel. "Our
study is the first to establish a mechanism by which S1P can be
exported out of mast cells and perhaps by cancer cells as well."
In previous research, Spiegel's team found that S1P levels are
significantly elevated in fluid collected from the lungs of asthmatic
patients after exposure to an allergen. Those findings led Spiegel's
team to believe that mast cells could be a source of S1P. Mast cells
are found in all body tissues and rapidly produce and secrete a number
of inflammatory substances such as histamine and S1P when activated by
an inflammatory stimulus. Spiegel said that S1P in turn amplifies
allergic and inflammatory responses. Therefore, S1P secreted from mast
cells can orchestrate many allergic responses, including asthma, she
said.
This work was supported by a grant from the National Institutes of
Health. The team included researchers Poulami Mitra, a Ph.D. candidate,
Carole A. Oskeritzian, Ph.D., Shawn G. Payne, Ph.D., from the VCU
Department of Biochemistry; Michael A. Beaven, Ph.D., a researcher with
the National Heart, Lung, and Blood Institute; and Sheldon Milstien,
Ph.D., a neuroscientist with the National Institute of Mental Health
---------------
S1P could help some psoratic alcoholic livers,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17058266&query_hl=15&itool=pubmed_docsum
And S1P is important to the immune system,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17050692&query_hl=15&itool=pubmed_docsum
-------------------------
http://news.biocompare.com/newsstory.asp?id=155760
PNAS Study Reveals Why Organs Fail Following Massive Trauma
10/17/2006
Source: University of Rochester Medical Center
National research effort addresses No. 1 cause of death among young
people
Massive trauma, say from a sabertooth tiger attack, meant immediate
death for the primitive human. Modern man is more likely to survive
severe injury caused by a car crash, gunshot or fall thanks to
high-tech emergency medicine. Unfortunately, the body does not know
what to do when it survives an injury that would have been fatal until
recently in human evolution. Nearly one third of the time, mechanisms
in place to protect people from disease misfire seven to ten days after
severe injury, causing multiple organ failure. That is one reason why
trauma is the leading cause of death for Americans aged 44 and younger.
A nationwide team of researchers is working urgently on the problem of
post-trauma immune system and organ failure, and has discovered several
new biochemical pathways that play a central role, according to a study
published today in the Proceedings of the National Academy of Sciences
(PNAS). Inventing new techniques along the way, the team is changing
emergency room guidelines, building the foundation for earlier
diagnosis of post-trauma organ failure and making possible the design
of drugs to reverse it.
Trauma has become a federal research priority because the survival rate
has not improved in 10 years. Excitement is growing, however, because
new evidence suggests that major diseases involving the immune system
share some of the same mechanisms and may be cured by manipulating the
same molecules. A protein called programmed cell death 1 (PD1), for
example, suggested by the PNAS paper as playing a role in post-trauma
organ failure, is also involved in the immune system breakdown leading
to AIDS, according to an article in the August edition of Nature.
"Our study proves for the first time that it is possible to identify
the genetic and protein changes in specific immune cells that play a
significant role in determining whether or not trauma is fatal," said
Carol L. Miller-Graziano, Ph.D., professor of Surgery and of
Microbiology & Immunology at the University of Rochester Medical
Center, and an author of the PNAS study. "Beyond trauma, we believe
that the techniques established here can provide insights into many
disease that involve human immune system failure."
No Respite from Toxins
The human immune system is actually two systems developed at different
points in human evolution. White blood cells of the more primitive
innate system, like neutrophils and macrophages, form the first line of
defense against disease. They swarm to the injury to engulf and destroy
bacteria with toxic molecules and biochemicals. Because these same
molecules and chemicals are also toxic to nearby human cells, the
innate response is normally shut down quickly by the onset of the more
time-consuming, precise and thorough adaptive immune system.
This second system pumps out an endless variety of immune cells on the
hope that one or more will be the right shape to link up with, and
become activated by, any invader encountered. When one of those immune
cells, called lymphocytes, recognizes a bacterium or virus presented by
the innate system, that lymphocyte expands into army of clones
specifically designed to attack the invader at hand. Unfortunately,
lymphocytes too are capable of mistakenly destroying human cells. Thus,
they have developed quality control mechanisms where they can choose to
stop expanding into an army (anergy) or to commit suicide (apoptosis).
The PNAS study offers new evidence that an overwhelming wave of
biochemical signals created by the innate response after massive trauma
can mistakenly trigger anergy and apoptosis, especially in T cell
lymphocytes, shutting down the adaptive response before it can begin.
Without the normal transition, the innate system continues to pump out
toxic chemicals (cytokines) and molecules (free radicals) that tear at
organs until they fail.
The goal of the current study was to identify the few genes and
proteins that play a central role in T-cell mediated immune and organ
failure. Given that severe trauma effects as many as 20 percent of the
20,000 or so human genes, finding the genes and proteins involved in T
cell anergy and apoptosis amid this storm has been a challenge.
Researchers took blood samples from 22 healthy subjects, and from 18
consenting patients who had experienced severe trauma, and were in the
midst of organ failure. The team then used unique, clinically
applicable techniques to separate out each immune cell type in the
patients' blood into pure samples for study. Only when researchers
compared pure samples of the same immune cell types (e.g. T cells to T
cells) did meaningful patterns emerge. The authors achieved a
statistically significant picture of the differences between
traumatized and healthy patients for the first time, and despite
skeptics that said it could not be done.
With pure samples in hand, researchers used microarray technology to
generate a long list of genes that change when a person undergoes
massive trauma. They then ran that list through a database of genetic
information to see which of the genes changed by trauma were listed in
the literature as having a role in T cell function. What emerged was a
map of the likely functions of hundreds of genes and proteins related
to T cell post-trauma dysfunction, and their likely partners in
signaling pathways. The final step was to demonstrate that the proteins
associated with those genes have an actual role in organ failure via
real-world biochemical tests.
Results showed that the expression of nearly 5,700 genes related to T
cell function is changed in cases of massive trauma, as are 2800 genes
related to the function of macrophages, partnering immune cells
necessary to T cell activation. Trauma had the most profound effect on
just 338 of the genes, an at least two-fold change in their expression,
the process by which the information they store is converted into
proteins that carry out bodily functions. Post-traumatic genetic
changes had two major effects on T cells: a marked increase in
regulatory protein pathways that diminished their function, and a
decrease in signals that turn them on, researchers said.
Whether T cells continue to multiply depends on the action of sensitive
receptor proteins on their surfaces. Some of the receptors, once
activated by signaling molecules, cause the T cell to multiply, while
others stop the process or cause the cell to self-destruct. Researchers
in the current study identified as many as 20 new receptors on the
surfaces of T cells or signaling molecules within T cells, that
increase their activity in the case of massive trauma to either cause
anergy or apoptosis. Each pathway represents a target for the design of
new drugs to reverse T cell shutdown.
The research for the current paper was conducted under the auspices of
a Large-Scale Collaborative Award from the National Institute of
General Medical Sciences (NIGMS), a division of the National Institutes
of Health. Also called "Glue Grants," the awards bring together large
teams of researchers to handle extremely complex problems. While the
PNAS study patient sample was small, techniques based on it are now
being used to study 150 patients per year throughout the Glue grant
infrastructure. The glue grant is an open access endeavor as well. The
results are posted publicly and hundreds of researchers have already
accessed the PNAS study results and applied them to their own projects.
The grant is organized into seven research cores, with the PNAS study
written within the Protein Analyses and Cell Biology (PACB) Core
working closely with the Genomics Core. PACB include analytical sites,
including the one led by Miller-Graziano. She oversaw the separation of
white blood cells into pure samples for the PNAS study, and continues
to determine cell surface protein expression for the larger Glue grant
team.
Along with Miller-Graziano, the University of Rochester Medical Center
team is led by Paul E. Bankey, M.D., Ph.D., director of Trauma and
Critical Care in the Department of Surgery, and includes Asit De,
Ph.D., assistant professor of surgery, and Krzysztof Laudanski, M.D., a
post-doctoral fellow. Fifteen authors from eight universities and one
pharmaceutical company collaborated on the PNAS article, including the
Stanford Human Genome Center.
The trauma glue grant was launched in 2001 with an original $30 million
award over five years, and has just been renewed with an additional $30
million in funding. The University of Rochester Medical Center team
will receive about $3.9 million for its role between the two periods of
the grant.
"These findings strikingly reveal that novel interactions among
signaling pathways can be deconstructed in hospitalized patient
populations," Bankey said. "For the first time, we can uncover changes
in cells that tell us which patients are recovering, and which are
getting worse, in almost any disease that involves the immune system."
------------------------
Defending against pathogens when they GAME the immunologic systems.
http://news.biocompare.com/newsstory.asp?id=155529
HIV Exploits Competition Among T-Cells
10/16/2006
Source: Rice University
Research points to new strategy for AIDS vaccination
A new HIV study shows how competition among the human immune system's T
cells allows the virus to escape destruction and eventually develop
into full-blown AIDS. The study, which employs a computer model of
simultaneous virus and immune system evolution, also suggests a new
strategy for vaccinating against the virus - a strategy that the
computer simulations suggest may prevent the final onset of AIDS.
The research, which is slated for publication in Physical Review
Letters, is available online at http://arxiv.org/abs/q-bio.PE/0610018.
"Competition among T cells exerts a small influence for most diseases,
but it's fatal for HIV," said study co-author Michael Deem, Rice
University's John W. Cox Professor in Biochemical and Genetic
Engineering and professor of physics and astronomy.
The new computer model, created by Deem and Guanyu Wang, now an
assistant professor of physics at George Washington University, is the
first to accurately reproduce all three stages of HIV infection. The
first is marked by an initial spike in virus production that's
immediately followed by dramatic drop as the immune system recognizes
the threat, mounts a defense and destroys most of the invading viruses.
The second phase is a long period of clinical latency that can last up
to 10 years. In this phase, a small amount of virus mutates fast enough
to escape initial detection and continues to mutate over time. The
third phase, AIDS, occurs when the virus has changed so much that the
body's T cells are no longer effective at keeping it in check.
Deem and Wang's computer model accurately describes all three phases of
HIV infection by incorporating a key component: competition among T
cells. The model includes two forms of competition. The first form
leads to a phenomenon known as deceptive imprinting, or original
antigenic sin. Original antigenic sin is the tendency for memory immune
cells produced in response to a first viral infection to suppress the
creation of new immune cells in response to a second infection by a
related strain. The second type of competition, immunodominance, occurs
when several viral strains simultaneously infect one person. In this
case, T cells compete to recognize the different strains. The winners
- the T cells that the body produces in mass quantities to fight the
disease - are the ones with the best overall record against the most
recogniztable strains. Among the losers, however, there may be T cells
that better control the other less recognizable, but still deadly,
strains.
"Once the immune system chooses a winning set of T cells, it has a
natural tendency to go with those cells when it's confronted by new
strains of the same disease in the future," Deem said. "For HIV, which
mutates rapidly, this is an Achilles' heel. We found a direct
correlation between the level of competition among T cells and the rate
at which the virus escaped."
Deem said one strategy to combat this effect would be to vaccinate
against the strains of HIV that will inevitably evolve in the body in a
manner that was designed to reduce immunodominance. One such strategy
- polytopic vaccination - involves giving vaccines against
different strains of the same disease simultaneously in different parts
of the body. The approach capitalizes on the fact that different lymph
nodes - the sites where T cells compete to be chosen as the winners
against a particular disease - act as collection points for different
parts of the body. Moreover, because it takes 4-5 days for T cells
produced in a lymph node to begin to leave it, the possibility exists
to set up simultaneous, independent competition against each of the
multiple strains that will evolve by injecting each strain
simultaneously so that they drain to different lymph nodes. In this
case, no single T cell is chosen as a winner. Instead, a separate
winner for each strain is picked in each affected lymph node before
immunodominance can come into play.
"In our simulations, this strategy appears effective at all but
eliminating competition among T cells," Deem said. "As a result, HIV
remained in a state of permanent latency and was never able to escape
the immune system's grasp to develop into AIDS."
------------------------------------
StoPPing the 1918 flu virus,
http://news.biocompare.com/newsstory.asp?id=155743
randall...
randall
http://www.medicalnewstoday.com/medicalnews.php?newsid=54586&nfid=nl
Gene Therapy Research Switches Off Joint Inflammation; Switches On
Genetic Process Of Joint Repair
Scientists at Case Western Reserve University School of Medicine and
Albany Medical College, together with Rainforest Nutritionals, Inc.
have demonstrated in a mini symposium held 18 Oct 2006 at the 14th
International Conference of the Inflammation Research Association (IRA)
that a blend of natural botanical products called Reparagen have turned
on the master repair gene, IGF-1, which is responsible for growing
human cartilage and restores joint function while blocking joint
destruction associated with inflammation. The IRA is the preeminent
meeting for inflammation investigators.
Mark J.S. Miller, Ph.D., M.B.A., Professor of Cardiovascular Sciences
and Pediatrics at Albany Medical College (NY) and head of the
Reparagen's Scientific Advisory Board said that, "Sixty six million
people have poor joint health; 20 million people suffer from
osteoarthritis. Compromised joint health is a major contributor to
comprised quality of life. No product of any kind has been able to
demonstrate this combination of actions. These findings have been
published in peer-review journals and presented to learned societies.
The commercialization of Reparagen has been supported by the US
government with a grant from the National Institutes of Health.
"Glucosamine is currently a gold standard in the natural product
approach to joint health with $1 billion in annual sales but recent
studies have questioned its effectiveness. There are no therapies on
the market today that work by activating the genes that control the
process of joint repair. Reparagen's approach is unique, in that it
switches 'off' the genes that control joint destruction and
inflammation while turning 'on' the process of inserting glucosamine
into new cartilage. Without this activated repair process glucosamine
cannot be effective.1 So this solves a riddle that has plagued
researchers for decades and corrects a problem that is exacerbated with
aging.
Multi-center, Randomized controlled Clinical Trial Underway
Dr. Mark J.S. Miller said that, "This trial is important because it
directly compares Reparagen with glucosamine in treating subjects with
moderate osteoarthritis. Glucosamine is both familiar to consumers and
healthcare providers and is the primary natural product approach to
osteoarthritis."
The double blind randomized controlled clinical trial will assess a
variety of pain, mobility and functional assessments in subjects with
moderate osteoarthritis of the knee. Prior to this clinical
investigation Reparagen was found to be the first natural product to
"silence" genes that promote joint damage while simultaneously
activating the repair gene, IGF-1, in human chondrocytes.2
The clinical study being conducted by clinical research organization
Santerra Pharmaceuticals, LLC (http://www.santerra-pharma.com/) was
submitted to Current Controlled Trials for review of the protocol and
assignment of an International Standardized Randomized Controlled Trial
Number (ISRCTN25438351).3
Rainforest Nutritionals, Inc. Vice President Paul Bobrowski emphasized
that, "Reparagen continues to set a new standard in the joint health
market, emphasized by this clinical study and the Current Controlled
Trials validation." Elaborating Bobrowski said, "We believe that
Reparagen's unique mechanism of action and its NIH innovation Award
makes it the alternative to glucosamine or chondroitin that consumers
can trust and try".
Coauthor Paul Bobrowski emphasized that "If joints are like a brick
wall made from bricks of glucosamine, and then it makes sense that to
rebuild a functional wall that you need the master bricklayer and not
just the simple approach of getting more bricks." Elaborating Bobrowski
said, "By activating the joints master bricklayer Reparagen offers a
more effective approach for regaining joint health."
###
1. The role of IGF-1 in joints is to improve the quality and quantity
of cartilage and it does this by inserting glucosamine and related
chemicals into the matrix. In inflammation this process is silenced
preventing repair and for this reason responsiveness to glucosamine is
highly variable. This research was published in the open access journal
BMC Complementary & Alternative Medicine
(http://www.biomedcentral.com/1472-6882/6/13).
2. Ibid.
3. Both Santerra and Rainforest Nutritionals believe in the importance
of exemplary science performed in open access manner and details of
this 8 week clinical study in 80 subjects can be found at
http://www.controlled-trials.com/ISRCTN25438351. Patients are taking
Reparagen,,Āµ orally with meals at the dose of 3 capsules of 600 mg a
day.
The Inflammation Research Association is a non-profit organization
instituted to bring together the world's top scientists and
investigators with an interest in inflammation research, to encourage
communication and discussion of scientific and technological advances
that can be used to develop new therapeutic agents for the wide
diversity of serious diseases with inflammatory processes.
An annotated background briefing document is available upon request.
About Park Labs, LLC
Founded in 2005, Park Labs is dedicated to bringing to market
innovative approaches to health and unmet consumer needs. For more
information see http://www.reparagen.com/
About Rainforest Nutritionals, Inc
Founded in 2002, Rainforest Nutritionals, Inc.
(http://www.rainforest-inc.com/) is dedicated to the development of
innovative natural therapeutics for the business-to-business market.
Rainforest Nutritionals, Inc was awarded an Innovation Research Award
(R43AG024733) from the NIH to foster the development and
commercialization of Reparagen.
---------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=54158&nfid=nl
Mayo Discovers Protein As Potential Tactic To Prevent Tumors
Mayo Clinic researchers have found that a protein that initiates a
"quality control check" during cell division also directs cell death
for those cells damaged during duplication. This knowledge represents a
potential "bulls eye" for targeting anti-tumor drugs. The findings
appear in the current issue of Science.
The researchers examined a protein called cyclin-dependent kinase 2
(CDK2), which works as a "quality control inspector." As normal cells
divide, they pause in the replication process when they find inaccurate
genetic code embedded in their DNA. The health and well-being of
offspring cells depends on accurate genetic code transfer from one
generation of cells to the next. The Mayo researchers showed that when
errors in genes are irreparable, CDK2 modifies another cellular protein
-- FOXO1 -- to send a signal that results in the death of the cell.
This protein-to-protein relationship invites targeted drug intervention
to control unregulated growth of cancer cells.
"Quality control within dividing cells is essential because mistakes
during duplication of the genetic code can lead to cancer," says Donald
Tindall, Ph.D., co-leader of the Mayo Clinic Cancer Center prostate
cancer research program. "CDK2 is a key protein component in the
cellular mechanism that leads to repair of damaged DNA."
If cells pass this quality control checkpoint, they can resume the
process of dividing into two daughter cells. If, however, major
irreparable discrepancies occur in the genetic code, cells are shunted
toward a molecular sequence that leads to death, or apoptosis. Cells
have the genetic knowledge to sacrifice themselves for the greater good
of the organism rather than to pass on errant genetic codes that can
lead to disease. Genetic errors that sneak past the cell's quality
control check-points can make the cell prone to develop into cancer.
How It Happens
The Mayo researchers documented that CDK2 infuses high energy into
another cellular protein, FOXO1, switching it on as the initial link in
a signal that tells the cell to set itself up for apoptosis. CDK2 adds
phosphorylation to a specific serine residue on the chain of amino
acids that make up FOXO1. In case of robust errors found in the genetic
code, CDK2 signals FOXO1 to explicitly call for the cell to produce a
set of proteins leading to apoptosis.
"If the cell has minor alterations in the DNA code that can be
repaired, those repairs are made," says first author Haojie Huang,
Ph.D. "If the genetic message cannot be repaired, our studies show that
CDK2 can initiate the steps necessary for cells to order the production
of genes involved with cell death, and the errant cell dies without
propagating its damaging genetic message to progeny cells of its own."
"As patients and their physicians seek to control or cure tumors,
research is providing new approaches to limiting cancer from growing
and spreading," Dr. Tindall said. "With this new understanding of the
biology driven by critical dual functions of CDK2, the cancer community
can focus on ways to regulate a mechanism that the cell contains to
prevent damaged genetic messages from being inherited and spread in
proliferating tumor cells."
--------------------------------
DNA ligase,
http://www.medicalnewstoday.com/medicalnews.php?newsid=54677&nfid=nl
---------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=54695&nfid=nl
Role For NF-kappa-B In Endothelial Cell Function
Sepsis is a life-threatening disease that can occur during bacterial or
viral infection of the blood. It can cause the barrier between the
blood and the surrounding tissues, which is formed by cells known as
endothelial cells, to become severely damaged, allowing the blood to
seep out into the tissues and the blood pressure to drop dramatically.
Conversely, tumors promote the proliferation and growth of endothelial
cells so that the tumor has its own blood supply that supplies it with
nutrients for growth. Therefore, understanding how endothelial cell
function is regulated is an area of intensive investigation.
In a study appearing online on October 19, in advance of publication in
the November print issue of the Journal of Clinical Investigation,
Christian Schindler and colleagues from Columbia University, New York,
show that in mice a regulator of gene expression known as NF-kappa-B
controls endothelial cell function in a model of shock and in a model
of cancer. Mice expressing an inhibitor of NF-kappa-B only in
endothelial cells were more susceptible to sepsis induced by
administration of the bacterial product LPS than normal mice. In
addition, tumors grew more rapidly in these mice than in normal mice.
This study implicates NF-kappa-B as a regulator of endothelial cells
function in health and disease, leading the authors to suggest that
care should be taken when developing therapeutic inhibitors of
NF-kappa-B as they might have hitherto unforeseen effects on
endothelial cells.
TITLE: NF-kappa-B regulation of endothelial cell function during
LPS-induced toxemia and cancer
---------------------------
Fixing the gut for IBS problems,
http://www.medicalnewstoday.com/medicalnews.php?newsid=54713&nfid=nl
&
http://www.anewibssolution.com/orderbook.htm
Ok. I see. He uses an antibiotic,
http://groups-beta.google.com/groups/search?q=Dr.+Mark+Pimentel+bacteria&qt_s=Search
& here it is,
http://www.medicalnewstoday.com/medicalnews.php?newsid=54344&nfid=nl
[...]
The study, "The Effect of a Nonabsorbed Oral Antibiotic (Rifaximin) on
the Symptoms of the Irritable Bowl Syndrome," is published in the
October 17, 2006, issue of Annals of Internal Medicine. The entire
article is available to the public on October 17, 2006,
at http://www.annals.org/cgi/content/full/145/8/557.
<sniP>
----------------------
Listening for skin cancer (what the heck will P sound like?)
http://www.medicalnewstoday.com/medicalnews.php?newsid=54271&nfid=nl
-----------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=54660&nfid=nl
The need to eat is initiated, in part, by a hormone known as ghrelin.
Although ghrelin is known to be produced in the gut and to trigger the
brain to promote eating, it remains to be determined precisely how
ghrelin affects different parts of the brain. Now, in a study appearing
online on October 19, in advance of publication in the December print
issue of the Journal of Clinical Investigation, researchers from Yale
University, have shown that in mice and rats ghrelin triggers the same
neurons as delicious food, sexual experience, and many recreational
drugs; that is, neurons that provide the sensation of pleasure and the
expectation of reward. These neurons produce dopamine and are located
in a region of the brain known as the ventral tegmental area (VTA).
Tamas Horvath and colleagues showed that ghrelin bound its receptor on
neurons of the VTA and triggered their production of dopamine.
Importantly, infusion of ghrelin into the VTA of rats increased their
food intake. Conversely, infusion of inhibitors of the ghrelin receptor
into the VTA of rats decreased the amount they consumed after a 24-hour
fast. This study identifies the VTA as a site of action for ghrelin to
induce food intake. As this region of the brain is also triggered by
many recreational drugs and is known to produce the expectation of
reward, the authors suggest that ghrelin stimulation of the VTA might
be involved in diseases of food abuse.
-----------------------------
The stress and depression gene (serotonin)
http://www.medicalnewstoday.com/medicalnews.php?newsid=54566&nfid=nl
---------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=54430&nfid=nl
Fisetin, a naturally occurring flavonoid commonly found in strawberries
and other fruits and vegetables, stimulates signaling pathways that
enhance long-term memory.
------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=54536&nfid=nl
"Ecstasy," or MDMA, can increase the survival of dopamine cells in the
brain during fetal development.
---------------------
Dopamine
http://www.medicalnewstoday.com/medicalnews.php?newsid=54240&nfid=nl
& the darker side of dopamine
http://www.medicalnewstoday.com/medicalnews.php?newsid=54587&nfid=nl
---------------
Long term memory and the neurotransmitter acetylcholine.
http://www.medicalnewstoday.com/medicalnews.php?newsid=54130&nfid=nl
-----------------
Eat green veggies to keep your brain younger,
http://www.medicalnewstoday.com/medicalnews.php?newsid=54844&nfid=nl
-----------------------
STOP TNF and inflammation with aPPles!
http://www.medicalnewstoday.com/medicalnews.php?newsid=54690&nfid=nl
&
http://tinyurl.com/wdu4h.
--------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=54230&nfid=nl
Food Allergies Could Be Fought With Friendly Bacteria In Alcoholic
Milkshake
Feeding babies alcoholic milk may help to protect against some food
allergies. Kefir, a traditional fermented drink, is consumed in Eastern
Europe as a health food, and is often used to wean babies, as it is
easily digested. Food allergy prevalence is especially high in children
under the age of three, with around 5-8% of infants at risk. Currently
the only treatment is avoidance of the problematic food.
"Friendly" bacteria in kefir may play a role in blocking the pathway
involved in allergic responses, Lisa Richards reports in Chemistry &
Industry, SCI's fortnightly magazine. Research published 16 October
2006(DOI 10.1002/jsfa2469) in the SCI's Journal of the Science of Food
and Agriculture has shown that the milk drink inhibits the allergen
specific antibody Immunoglobulin E (IgE). IgE is involved in immune
responses to inactivate organisms that might cause disease. However, in
the presence of allergens it can also activate cells responsible for
the release of histamine, a chemical which stimulates allergic
responses, such as inflammation and constriction of airways.
Ji-Ruei Liu's team of scientists at the National Formosa University,
Yunlin, Taiwan, fed mice the milky drink, and found that after 3 weeks,
the amount of ovalbumin (OVA) specific IgE was reduced three-fold.
Ovalbumin is an allergenic protein found in egg whites, which cause
most allergies in young children. Kefir is also reported to prevent
food antigens from passing through the intestinal wall.
Liu believes that the milky drink could be a promising tool in the
prevention of allergies. "In the future, maybe we can screen out the
certain components (bacterial strains or bioactive peptides) from kefir
and utilize them in medicine," he said.
----------------------------
randall...
randall
Stuff to go with the stuff in p news...
Or not.
Your lymph and liver cells are giving up their secret conversations.
Will it include a trick or treat to clear I.M.I.D's?
http://www.medicalnewstoday.com/medicalnews.php?newsid=55698&nfid=nl
[...]
The authors propose the term "trans-endothelial hepatocyte-lymphocyte
interactions" (TEHLI) to describe these interactions.
The discovery of TEHLI is the first demonstration by electron
microscopy of the interaction between naive T cells and liver cells in
a living organism, which shows that the liver is an exception to the
rule that T cells need to be activated by professional APCs in order to
cross the endothelial barrier, and that hepatocytes can function as
APCs
<sniP>
------------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=55360&nfid=nl
Identification Of Key Molecular Signaling Switch Involved In Allergic
Disease: May Provide A New Target For Treatment Of Allergic Reactions
A research team has identified a key enzyme responsible for triggering
a chain of events that results in allergic reaction, according to new
study findings published online this week in Nature Immunology.
The work by researchers from Virginia Commonwealth University, the
Hospital for Special Surgery and Weill Cornell Medical College in New
York sets the stage for development of new strategies and target
therapies that control allergic disease - the sixth leading cause of
chronic disease in the United States.
Allergic diseases such as asthma and hay fever are problematic for
about 30 percent of the population in the developed world. Researchers
have developed various treatments to control allergy, but no cure has
been found.
The team has demonstrated, for the first time, the role of a
proteolytic enzyme called ADAM10 that releases a major allergy
regulatory protein from the surface of cells and thereby promotes a
stronger allergic response. The identification of drugs that inhibit
ADAM10's ability to release this molecule could revolutionize treatment
of asthma and allergic disease.
"Our research, for the first time, may represent a treatment strategy
to prevent, rather than simply control IgE-mediated allergy," said
Daniel Conrad, Ph.D., a professor in VCU's Department of Microbiology
and Immunology. Conrad directed the research conducted at VCU. IgE is
an antibody known to trigger Type I allergic disease.
"Understanding ADAM10's role in allergic disease makes it a potential
target for the design of drugs to treat asthma and allergic disease,"
he said.
According to Conrad, the outcome of allergic disease can be modulated
by high levels of the regulatory protein, known as CD23, which
ultimately results in a decreased production of IgE. He said that when
the regulatory protein is released from the cell surface by ADAM10
there is an increase in the production of IgE and therefore, increased
allergy.
"These exciting results extend the known functions of ADAMs in
development and disease. We hope our results will stimulate new
research into how to block or activate the function of ADAMs involved
in human disease, including allergic response, cancer and rheumatoid
arthritis," said Carl P. Blobel, M.D., Ph.D, chair of the Arthritis and
Tissue Degeneration Program at the Hospital for Special Surgery, and
professor of Medicine and of Physiology and Biophysics at Weill Cornell
Medical College. Blobel directed the research conducted at Weill
Cornell.
According to Blobel, in addition to the critical role of ADAM10 in
allergic disease through processing of CD23, ADAMs are also key
molecules in cancer and rheumatoid arthritis. For example, he said,
ADAMs are essential for activating the epidermal growth factor
receptor, an established target for the treatment of cancers, such as
colon cancer. Moreover, ADAMs release tumor necrosis factor alpha,
currently the major target for treatment of rheumatoid arthritis.
Since the 1970s Conrad has been investigating the basic mechanism
involved in allergic disease. Blobel has been investigating ADAM
proteases since their discovery in the early 1990s.
-------------------------
New thinking for RA. Is it an autoimmune condition? Only your genes
know for sure!
http://www.medicalnewstoday.com/medicalnews.php?newsid=55603&nfid=nl
Study Offers New Perspective On Nitric Oxide Signaling In Rheumatoid
Arthritis
Scientists at the University of Michigan Medical School have found
evidence that challenges current thinking about the cause of rheumatoid
arthritis (RA), a chronic inflammatory disease that damages joints,
causes pain, loss of movement, and bone deformities in 2.1 million
Americans.
Published in the November 2006 issue of Arthritis and Rheumatism,
results from the study could help answer questions that have puzzled
scientists for more than 20 years:
Why do nearly 95 percent of RA patients have a common sequence of DNA,
which scientists call a shared epitope, and why do patients with this
DNA sequence have more severe forms of the disease than patients
without it?
Most researchers believe that RA is an autoimmune disorder, because the
shared epitope is located in an area of the human genome that codes for
proteins involved in the immune system's recognition of antigens.
Antigens are like little name tags on the surfaces of cells. They help
the immune system recognize what belongs in our bodies and what
doesn't. The immune system will attack foreign antigens. For example,
without closely matched antigens, a transplant patient's immune system
will reject a donated organ.
"Although the hypothesis that RA is an autoimmune disorder is widely
accepted, there is no convincing evidence that it is correct," says
Joseph Holoshitz, M.D., associate professor of internal medicine at U-M
Medical School who directed the study. "We see this same type of
association with HLA genes in other diseases, which we know are not
autoimmune diseases."
Holoshitz and his colleagues discovered that the shared epitope can
trigger a signaling cascade that leads to increased production of
nitric oxide in other cells. A gas produced by several types of cells
in the body, nitric oxide is an important signaling molecule.
"Our findings suggest this activity is unrelated to antigen
presentation," says Holoshitz. "This is the first direct evidence that
the shared epitope may be responsible for the overproduction of nitric
oxide seen in patients with RA."
Overproduction of NO inhibits apoptosis - the natural process that
leads to cell death. Resistance to apoptosis is a common trait found in
cells lining the joints of RA patients, and is believed to lead to
disease symptoms.
In the U-M study, cells from individuals with the shared epitope were
completely resistant to cell death when compared to samples from
individuals without the shared epitope.
"It was previously postulated that nitric oxide plays a role in RA,
since patients have higher levels of it in their joint tissue. When we
looked at the rate of NO generation in these patients, we found that it
was significantly higher for people with the shared epitope," says
Holoshitz.
The findings offer scientists a new way of viewing other diseases, in
addition to RA. For example, narcolepsy and certain types of leukemia
are strongly associated with HLA genes, yet there is no convincing
evidence that they are autoimmune diseases. According to Holoshitz,
further research into HLA genes and their function could offer new
insights into the cause of these diseases.
Holoshitz cautions that, although the association between the shared
epitope and RA is consistently found among many ethnic groups, five to
10 percent of all RA patients are shared epitope-negative. Further
studies are needed to examine other possible causes of nitric oxide
overproduction in RA.
The research was supported by the National Institutes of Health, the
Arthritis Foundation, and the University of Michigan Biotechnology
Development Fund.
Contributing authors include first author Song Ling, Ph.D., a research
investigator in the departmental of internal medicine, U-M Medical
School; Angela Lai, a U-M undergraduate student; and Olga Borschukova
and Paul Pumpens from the Biomedical Research and Study Center,
University of Latvia.
Citation: Arthritis & Rheumatism: (54) 11, pp. 3423-3432, November 2006
----------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=55464&nfid=nl
Spectrin and ankyrin are two essential proteins acting like bricks and
mortar to shape and fortify cell membranes <sniP>
-------------------------------
Curcumin good for PsA and arthritis.
http://www.medicalnewstoday.com/medicalnews.php?newsid=55478&nfid=nl
Turmeric Prevents Experimental Rheumatoid Arthritis, Bone Loss,
University Of Arizona Study Shows
An ancient spice, long used in traditional Asian medicine, may hold
promise for the prevention of both rheumatoid arthritis and
osteoporosis, according to a recently completed study at The University
of Arizona College of Medicine.
Turmeric, the spice that flavors and gives its yellow color to many
curries and other foods, has been used for centuries by practitioners
of Ayurvedic medicine to treat inflammatory disorders. Turmeric extract
containing the ingredient curcumin is marketed widely in the Western
world as a dietary supplement for the treatment and prevention of a
variety of disorders, including arthritis.
At the UA College of Medicine, Janet L. Funk, MD, working with Barbara
N. Timmermann, PhD, then-director of the National Institutes of Health
(NIH)-funded Arizona Center for Phytomedicine Research at the UA, set
out to determine whether (and how) turmeric works as an anti-arthritic.
They began by preparing their own extracts from the rhizome, or root,
of the plant, providing themselves with well-characterized materials to
test and to compare with commercially available products. (Dr.
Timmermann since has joined the faculty of the University of Kansas,
Lawrence, Kan.)
Dr. Funk and her colleagues then tested in animal models a whole
extract of turmeric root, only the essential oils, and an oil-depleted
extract containing the three major curcuminoids found in the rhizome.
Of the three extracts, the one containing the major curcuminoids was
most similar in chemical composition to commercially available turmeric
dietary supplements. It also was the most effective, completely
inhibiting the onset of rheumatoid arthritis.
Dr. Funk, an endocrinologist in the UA Department of Medicine, says
this study provides several noteworthy "firsts." Completed with the
researchers' own prepared, well-defined extracts, the study represents
the first documentation of the chemical composition of a
curcumin-containing extract tested in a living organism, in vivo, for
anti-arthritic efficacy. It also provides the first evidence of
anti-arthritic efficacy of a complex turmeric extract that is analogous
in composition to turmeric dietary supplements.
The significance, she explains, is that translating the results of
trials such as these to clinical use depends on accurate information
about the chemical content and biological activity of the botanical
supplements available for use. This work paves the way for the
preclinical and clinical trials needed before turmeric supplements can
be recommended for medicinal use in preventing or suppressing
rheumatoid arthritis.
This study also provides the first in vivo documentation of a mechanism
of action - how curcumin-containing extracts protect against arthritis.
The researchers found that the curcuminoid extract inhibits a
transcription factor called NF-KB from being activated in the joint. A
transcription factor is a protein that controls when genes are switched
on or off. Once the transcription factor NF-KB is activated, or turned
on, it binds to genes and enhances production of inflammatory proteins,
destructive to the joint. The finding that curcuminoid extract inhibits
activation of NF-KB suggests that turmeric dietary supplements share
the same mechanism of action as anti-arthritic pharmaceuticals under
development that target NF-KB. It also suggests that turmeric may have
a use in other inflammatory disorders, such as asthma, multiple
sclerosis and inflammatory bowel disease.
In addition to preventing joint inflammation, Dr. Funk's study shows
that the curcuminoid extract blocked the pathway that affects bone
resorption. Noting that bone loss associated with osteoporosis in women
typically begins before the onset of menopause, she has begun work on
another NIH-funded study to determine whether turmeric taken as a
dietary supplement during perimenopause can prevent bone loss and
osteoporosis. Both of the studies are supported by the National Center
for Complementary and Alternative Medicine (NCCAM) and the Office of
Dietary Supplements (ODS), both of the NIH.
An initial publication of the rheumatoid arthritis study results in the
Journal of Natural Products, which was among the most-accessed articles
from April-June 2006 in this prestigious American Chemical Society
journal, is being followed by more detailed study results, which will
appear in the November 2006 issue of the American College of
Rheumatology flagship journal, Arthritis and Rheumatism. The article,
"Efficacy and Mechanism of Action of Turmeric Supplements in the
Treatment of Experimental Arthritis," appeared in the online issue of
Arthritis and Rheumatism Oct. 30, 2006.
----------------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=55413&nfid=nl
[...]
The Company believes that this drug class has the potential to be
additive to the class of hyperlipidemia drugs known as "statins", and
preclinical data suggests that MB07811 could be as effective at
lowering serum cholesterol as this important drug class <sniP>
----------------------------------
Anti prion compound 15X's stronger then drugs being tested
now.(quinacrine)
http://www.medicalnewstoday.com/medicalnews.php?newsid=55490&nfid=nl
-------------------------------
Should you take coenzyme Q10 (coq10)?
http://www.medicalnewstoday.com/medicalnews.php?newsid=55867&nfid=nl
------------------------------
http://www.medicalnewstoday.com/medicalnews.php?newsid=55424&nfid=nl
[...]
The multicenter research team confirmed the involvement of one gene,
called Nod2 or CARD15, and discovered that a defect of the
interleukin-23 receptor gene (IL-23R) also led to the development of
Crohn's disease. <sniP>
--------------------------------
Don't go to be lonely. Or you'll wake up with higher cortisol levels.
http://www.medicalnewstoday.com/medicalnews.php?newsid=55455&nfid=nl
--------------------------------
A really good Cream for atopy problems?
http://www.medicalnewstoday.com/medicalnews.php?newsid=55510&nfid=nl
[...]
The product, 'Higuard', is the first Rx-to-OTC switch product of
azelastine hydrochloride, an anti-allergy compound originally approved
for prescription use. It is also effective in alleviating allergyc
symptoms including rhinitis caused by pollens or house dusts and skin
problems such as utricaria and eczema.
The active ingredient of Higuard azelastine hydrochloride exhibits
anti-allergic effects by inhibiting and releasing leukotriens and
histamine that cause allergy, relieving allergic symptoms including
rhinitis (sneezing, runny and stuffy nose) and skin problems
(urticaria, eczema, etc). <sniP>
--------------------------------
Stronger antibiotics. Lantibiotics
http://www.medicalnewstoday.com/medicalnews.php?newsid=55451&nfid=nl
--------------------------
A cure for multiple sclerosis soon?
http://www.medicalnewstoday.com/medicalnews.php?newsid=55920&nfid=nl
& Fixed the myelin already
http://www.medicalnewstoday.com/medicalnews.php?newsid=55770&nfid=nl
-----------------------------
randall
randall
The quest for natural anti-inflammation substances o'er land and sea
goes on.
Biologist Craig Venter is scouring the sea for DNA.
http://www.signonsandiego.com/news/science/20061109-9999-7m9venter.html
[...]
"We're sort of scratching the surface of the ocean, and with Craig's
leadership, we have this window into the (genetic) information of the
ocean."
[...]
Venter and UCSD announced a joint venture to accelerate research into
the DNA of ocean microbes and build a computer infrastructure to manage
the vast amount of information generated from that effort. The project
is titled CAMERA, short for Community Cyberinfrastructure for Advanced
Marine Microbial Ecology Research. It is being funded by a $24.5
million grant from the Gordon and Betty Moore Foundation.
"The ocean represents a frontier for Venter and for us, and
collaborating on this is a smart thing to do," said John Orcutt,
UCSD's associate vice chancellor for government research relations and
director of research innovation initiatives.
The Scripps Institution of Oceanography runs a research program on the
genetics of marine life. The newly proposed partnership with Venter
would elevate what many already see as a world-class program, said Bill
Gerwick, a lead researcher at the institution's Center for Marine
Biotechnology & Biomedicine.
"We're going to make use of (Venter's) incredible ability to sequence
genes," said Gerwick, who is also a professor at UCSD's Skaggs School
of Pharmacy and Pharmaceutical Sciences. "We have just dozens of
projects awaiting sequencing."
Gerwick studies the DNA of cyanobacteria, a marine algae that someday
may be used in the development of drugs. Scripps has compiled one of
the world's largest - if not the largest - collections of
cyanobacteria, and researchers are eager to map out the DNA of these
organisms, Gerwick said.
"(Venter) is a very high-profile scientist and will bring a lot of
talent and recognition with him," Gerwick said. "Things are
_____________snowballing."___________________
(If they knew this was going to be posted in a P newsgroup they'd enjoy
the irony!)
The Scripps Institution is already one of the most prestigious
oceanographic labs in the world, Haymet said, and accelerating work in
ocean genomics will further elevate its profile.
"It's just a way of reinforcing La Jolla as one of the centers for
modern marine science," he said.
-------------------------------------------
Till a super computer can figure out all the folds in these proteins,
using them
as templates for future drugs won't become a reality.
Natural Compounds Block Autoimmune Response In Diabetes, Arthritis
11/6/2006
Source: University of California - Irvine
UCI study identifies how treatment can limit impact of T cells in
autoimmune diseases
Natural compounds derived from a sea anemone extract and a shrub plant
have been found to block the autoimmune disease response in type-1
diabetes and rheumatoid arthritis, according to University of
California, Irvine researchers.
The study shows both in human and animal tests how these compounds work
to deter the effect of autoimmune T-cells, white blood cells that
attack the body. The goal, according to UCI researchers, is to develop
new treatments from these compounds that will target these destructive
T-cells while allowing other white blood cells to fight disease and
infection.
Study results appear Nov. 6-10 in the Early Online Edition of the
Proceedings of the National Academy of Sciences.
The study, led by UC Irvine School of Medicine researchers George
Chandy and Christine Beeton, identifies how these compounds work
against a type of white blood cells called effector memory T
lymphocytes, which play a major role in autoimmunity. Both compounds
block an ion channel in these cells that prevents the cells from
proliferating and producing chemicals called cytokines that attack the
body during autoimmune disease states.
"Autoimmune diseases affect millions of Americans, and any new
therapies that can aid them will have great significance," Chandy said.
"What's promising about this study is that we identified a protein
target on the T-cells that promote autoimmune activity and the
compounds that can selectively block the target and shut down the
destructive cells."
White blood cells patrol the body to fight against cancer and
infections, but if some of these cells turn against the body they are
meant to protect, they cause autoimmune diseases. Millions of people
worldwide are afflicted with disabling autoimmune disorders. Two
examples of this large class of diseases are type-1 diabetes, in which
white blood cells attack the pancreas, and rheumatoid arthritis, in
which the joints are attacked.
In their study, the UCI researchers used modified compounds derived
from the rue plant (PAP-1) and a Cuban sea anemone extract (SL5), both
of which block the ion channel in the destructive T-cells.
In one set of tests using blood samples from type-1 diabetes patients
and joint fluid from people with rheumatoid arthritis, the researchers
found that both compounds suppressed the function of the autoimmune
T-cells without affecting other T-cells that fight infections.
In another set of tests using rats, the compound from the rue shrub
plant delayed the onset and reduced the incidence of disease in
diabetic rats, while the venom compound stopped the progression of the
disease and improved the joint function of rats with experimental
autoimmune arthritis. In these rat tests, the compounds were nontoxic.
The Chandy laboratory previously discovered that SL5 compound was
effective in treating rats with an experimental model of multiple
sclerosis, another devastating autoimmune disease. Preclinical safety
studies on PAP-1 and SL5 are under way in collaboration with AIRMID, a
biotech company in the San Francisco Bay Area.
"We began our work on these natural products many years ago when we
came across a report that described the beneficial effect of a scorpion
sting on a patient with multiple sclerosis," Beeton said. "This work
also speaks to the importance of protecting our plant and animal
biodiversity -- you never know where a new medicine will come from."
Heike Wulff from University of California, Davis is a co-lead author,
and other authors from UCI, UC Davis, Johns Hopkins University, Bachem
Biosciences and the Benaroya Research Institute in Seattle are noted in
the study text. The National Institutes of Health, American Diabetes
Association, Juvenile Diabetes Research Foundation, National Multiple
Sclerosis Society, Arthritis National Research Foundation and David
Israelsky provided support for this study.
About type-1 diabetes and rheumatoid arthritis: The American Diabetes
Association estimates that type-1 diabetes mellitus, also known as
juvenile diabetes, affects one in every 400 or 600 children and
adolescents in the U.S. It is characterized by a destruction of the
cells that produce insulin in the pancreas. Without enough insulin, the
body cannot correctly regulate levels of blood glucose, a major source
of energy for the body. Type-1 diabetes can lead to serious
complications such as heart disease, blindness, and nerve or kidney
damage.
In rheumatoid arthritis, white blood cells induce inflammation in the
joints, leading to muscle and joint aches, stiffness, and fatigue.
According to the Arthritis Foundation, rheumatoid arthritis is one of
the most serious and disabling types, affecting mostly women. An
estimated 2.1 million people in the U.S. have rheumatoid arthritis.
Some recent studies have suggested that the overall number of new cases
of rheumatoid arthritis actually may be going down.
-------------
What is the human to sea urchin link in regards to our DNA?
http://www.medicalnewstoday.com/medicalnews.php?newsid=56327
The Sea Urchin Genome Is Sequenced: Scientists Make Good Use Of Its
Surprising Similarity To Humans
Who would have guessed that the lowly sea urchin, that brain-less,
limb-less porcupine of the sea, would be the star of a multi-million
dollar, worldwide effort to map out every letter of its genetic code?
Or that the information gathered in that effort may eventually lead to
new treatments for cancer, infertility, blindness, and diseases like
muscular dystrophy and Huntington's Disease?
James Coffman, Ph.D., of the Mount Desert Island Biological Laboratory
in Bar Harbor was one of the scientists who helped decode the 814
million pairs of nucleotide bases in the sea urchin's chromosomes. The
Human Genome Sequencing Center at Baylor College of Medicine in Texas
led the project and announced the completion of the three-year project
today. Having the complete genome, Coffman says, "makes doing research
on urchins so much easier."
Why would anyone want to do biomedical research on sea urchins?
According to Coffman, sea urchins are remarkably similar to humans in
many ways, sharing most of the same gene families, and yet differ in a
few critical areas besides the obvious physical ones. For one thing,
sea urchins have a "extraordinarily complex innate immune system" which
is not based on antibodies, like that of jawed vertebrates, but is
effective enough to give sea urchins a surprisingly long life span of
up to a hundred years or more <sniP>
-------------------
randall.. the whole thing is SNOWballing. LOL And don't call me
snowFLAKE!
randall
>
> http://www.medicalnewstoday.com/medicalnews.php?newsid=56327
[...]
"The sea urchin reminds us of the underlying unity of all life on
earth," notes Erica Sodergren, Ph.D., co-leader of the sequencing
project. At MDIBL, Dr. Coffman is hoping to exploit that unity to
ultimately find new treatments for human diseases and is studying a sea
urchin member of one of those shared families of genes known as the
"Runx" genes. In vertebrates this family of genes is known to be
important for developmental processes such as bone and blood formation,
and its mutations are associated with bone disorders and a common form
of childhood leukemia.
------------------
http://alaskaunderseatours.com/photos/Red-Sea-Urchin.jpg
Besides living for up to a 100 years, provided some sushi gourmand
doesn't find him,
these urchin spiny critters could help out in the ______runx____ gene
department.
I almost missed that little gem.
And Dr. Bowcock may be helpful there.
http://groups-beta.google.com/groups/search?qt_s=1&q=bowcock+runx
--------------
And,
don't forget, Bowcock and Krueger may very well lead the pack in the P
cure department.
http://groups-beta.google.com/groups/search?q=bowcock+krueger+psoriasis&qt_s=Search
Note: I was watching the indy 500 while writing that first hit. LOL
Not a bad metaphor huh? I sure hope and pray that the finish line is
closer then J thinks. LOL
randall....OTOH it's not the darkest P days!
randall
This morning I was thinking one way and now i've gone this other
direction.
The Runx gene thing is on the table.
So, here's the latest buzz around genetics,
http://www.timesonline.co.uk/article/0,,2-2455248,00.html
Neanderthal musings have been either pejorative, as in the p genes or
as a slur in this group.
Mostly by me. lol
Now the tide turns for their genes to be looked at closer.
What will that tell us?
After all they did die out,
http://www.archaeology.org/online/news/jpegs/dna.jpeg
But now comes the actual DNA research in this area. And these dudes are
even closer to us then
chimps, like Larry, moe and curly,
http://www.stoogeworld.com/_Videography/Editing/Cash%20and%20Carry.jpg
So, while we diverged from real chimps 5 million years ago, we only
broke away from the
neanderthals 550,000 to 690,000 years ago. Sadly, stooges are here to
stay. LOL
see: http://www.ecotao.com/holism/hu_neand.htm
Now comes the time to figure out what makes a modern day human the
way he is. Based of course on what he isn't anymore! Stooges beware,
http://news.nationalgeographic.com/news/2006/11/061115-neanderthal-dna.html
http://blogs.chron.com/sciguy/archives/2006/11/hello_mr_neande.html
Why did they die out? What genes are in play?
http://en.wikipedia.org/wiki/Neanderthal
Will a MHC or HLA gene be identified?
http://en.wikipedia.org/wiki/Major_histocompatibility_complex
http://www.gnxp.com/MT2/archives/003580.html
http://www.google.com/search?hl=en&lr=&q=mhc+hla+psoriasis+chromosome&btnG=Search
http://www.google.com/search?hl=en&lr=&q=mhc+hla+psoriasis+chromosome+early+late+onset&btnG=Search
Runx as the kicker,
http://www.google.com/search?hl=en&lr=&q=mhc+hla+psoriasis+chromosome+early+late+onset+runx&btnG=Search
And since this is a runx thread by default. Let's look at evolution and
runx.
The evolution of Runx genes I. A comparative study of sequences from
phylogenetically diverse model organisms.
* Rennert J,
* Coffman JA,
* Mushegian AR,
* Robertson AJ.
Stowers Institute for Medical Research, 1000 E, 50th Street, Kansas
City, MO 64110, USA. jessr...@msn.com
BACKGROUND: Runx genes encode proteins defined by the highly conserved
Runt DNA-binding domain. Studies of Runx genes and proteins in model
organisms indicate that they are key transcriptional regulators of
animal development. However, little is known about Runx gene evolution.
RESULTS: A phylogenetically broad sampling of publicly available Runx
gene sequences was collected. In addition to the published sequences
from mouse, sea urchin, Drosophila melanogaster and Caenorhabditis
elegans, we collected several previously uncharacterised Runx sequences
from public genome sequence databases. Among deuterostomes, mouse and
pufferfish each contain three Runx genes, while the tunicate Ciona
intestinalis and the sea urchin Strongylocentrotus purpuratus were each
found to have only one Runx gene. Among protostomes, C. elegans has a
single Runx gene, while Anopheles gambiae has three and D. melanogaster
has four, including two genes that have not been previously described.
Comparative sequence analysis reveals two highly conserved introns, one
within and one just downstream of the Runt domain. All vertebrate Runx
genes utilize two alternative promoters. CONCLUSIONS: In the current
public sequence database, the Runt domain is found only in bilaterians,
suggesting that it may be a metazoan invention. Bilaterians appear to
ancestrally contain a single Runx gene, suggesting that the multiple
Runx genes in vertebrates and insects arose by independent duplication
events within those respective lineages. At least two introns were
present in the primordial bilaterian Runx gene. Alternative promoter
usage arose prior to the duplication events that gave rise to three
Runx genes in vertebrates.
PMID: 12659662
And all leading to this grail moment.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16904090&query_hl=11&itool=pubmed_docsum
Runx-dependent regulation of G-protein gamma3 expression in T-cells.
* Dubeykovskiy A,
* McWhinney C,
* Robishaw JD.
Weis Center for Research, Geisinger Clinic, Danville, PA 17822-2614,
USA.
Heterotrimeric G-proteins control diverse biological processes by
conveying signals from seven-transmembrane receptors to intracellular
effectors. Although their signaling roles were originally ascribed to
their GTP-bound alpha-subunits, more recent evidence points to the
equally active roles played by their betagamma-dimers. To elucidate the
individual contributions of their gamma-subtypes, we used a gene
targeting approach to show that mice lacking the gamma3-subtype display
a defective T-cell dependent immune response. To identify the cellular
basis for this defect, we demonstrated that gamma3-mRNA is strongly
induced in activated CD4+ T-cells. To determine the mechanism for this
regulated expression, we used several strategies to identify the
importance of a Runx consensus sequence element in the first intron of
the gamma3 gene and the Runx1 protein. Overall, these data provide the
first genetic evidence for the tight regulation and involvement of the
G protein gamma3-subtype in mounting an effective immune response in
mice.
PMID: 16904090
And this is why we want to compare chimp and neanderthal dna. It's a
RUNX thingy.
More so it's a P thingy.
And finding it means finding the grail.
The p grail anyway.
Which ever one is really worth looking for?
You can find yourself right now. LOL
You may not be a direct descendant of the da winky code but
if your even mildly in to homeopathics, we've all had molecules of
every saint course thru us. So we are all divine provided your
receptive.
But what of those who got the stooge genes?
Time will tell.
randall.... musings of a psoriatic in quest of the GRAIL!
randall
randall wrote:
> Hi,
>
> This morning I was thinking one way and now i've gone this other
> direction.
>
> The Runx gene thing is on the table.
>
> So, here's the latest buzz around genetics,
<sniP>
The scientist can map all of our P genes and still come uP short.
So, what are they missing?
Maybe we aren't missing so much as having to much?
A new look at disease and psoriasis from a genetic point of view.
Looking at the missing pages?
Or the CNV's.
http://en.wiktionary.org/wiki/copy-number_variant
http://www.washingtonpost.com/wp-dyn/content/article/2006/11/22/AR2006112201082.html
New map on human genetic variation unveiled
By Patricia Reaney
Reuters
Wednesday, November 22, 2006; 1:13 PM
LONDON (Reuters) - An international team of scientists unveiled on
Wednesday a new human genetic map, or "book of life," that fills in
missing pages and chapters to explain how genes are involved in common
diseases.
Instead of showing single variations in human DNA that make people
unique, the map looks at differences in duplications and deletions of
large DNA segments known as copy number variants (CNVs) which can help
explain why some people are susceptible to illnesses such as AIDS and
others are not.
"We're a patchwork of DNA sequences, gains and losses," said Dr Charles
Lee, of the Brigham and Women's Hospital and Harvard Medical School in
Boston, Massachusetts, speaking at a news conference.
Scientists from more than a dozen centers around the world identified
about 3,000 genes with variations in the number of copies of specific
DNA segments. The changes can influence gene activity and disease
susceptibility.
The Human Genome Project mapped the billions of letters that make up
the human genetic code. Scientists later refined the map by looking for
single variations called SNPs, single nucleotide polymorphisms, in the
arrangement of those letters which make individuals unique.
The CNV map gives researchers a different way to look for genes linked
to diseases by identifying gains, losses and alterations in the genome.
"Copy number variation is complex. There are different types," said Dr
Matthew Hurles, of the Wellcome Trust Sanger Institute in England.
"In addition to deletions and duplications, there are more complex
forms where a gene can be present in one individual in multiple copies
in a tandem array," he told the news conference.
He added that resistance to infection by HIV, which causes AIDS, is
determined in part by multiple copies of the gene CCL3L1, which cannot
be seen on an SNP map.
NEW TOOLS
The scientists, whose findings are reported in the journals Nature,
Nature Genetics and Genome Research, compiled the CNV map by comparing
DNA from 270 healthy people in China, Japan, Nigeria and the United
States.
The consortium identified 1,447 different CNVs that covered about 12
percent of the human genome. About 285 of them are associated with
diseases. CNV duplication is linked to schizophrenia, psoriasis,
coronary heart disease and congenital cataracts.
"With these new tools, we and our clinical colleagues are able to find
previously undetectable deletions or duplications of the genome in a
patient. The CNV map now allows us to identify which of these changes
are unique to the disease," said Dr Nigel Carter, of the Wellcome Trust
Sanger Institute.
The scientists have also developed a database called DECIPHER that will
enable researchers around the world to use the Internet to submit
information on patients with CNV details. The information will be
mapped on to the human genome in the public browser.
"This important work will help identify genetic causes of many
diseases," said Dr Mark Walport, director of the Wellcome Trust, in a
statement.
(((((((((((((((((((((((((((((((((((((((()))))))))))))))))))))))))))))))))))))))
I guess we look at cnv now.
http://www.newscientist.com/article/dn10646-gene-duplications-may-define-who-you-are-.html
Gene duplications may define who you are
* 18:00 22 November 2006
* NewScientist.com news service
* Debora MacKenzie
What makes people different may not just be their different genes, but
how many copies they have of each one, and how many stretches of DNA
are "missing".
Two separate studies of the human genome have revealed an unsuspected
amount of variation between people in the number of copies of genes
they have. Such variations appear to involve as much as 12% of our DNA,
and raise questions about what constitutes a "normal" genome.
Originally, the differences between individuals were thought simply to
be the result of mutations, whereby single bases in a DNA strand
change, which can cause small changes in the proteins the DNA codes
for.
Then in the 1990s scientists discovered that people also differed in
the number of copies of genes they had, with large chunks of one
person's DNA being duplicated or deleted when compared to
another's. Extra copies of identical genes can even cause disease
with no mutation involved (see Genomics: We are all numbers).
What is normal?
How much of this duplication and deletion occurs is not clear, but now
two separate groups of researchers have found that it involves more of
the genome than anyone suspected.
Stephen Scherer at the Hospital for Sick Children in Toronto, Canada,
and colleagues sought out differently deleted or duplicated chunks of
DNA in the two complete human genome sequences so far produced. They
discovered that nearly 24 million nucleotides are involved in such
"copy number variants" (CNVs).
They conclude that adding this kind of variation to the single-base
mutations we already knew about means "significantly more variation
exists between humans than was previously estimated".As personalised
genetic sequencing becomes more common, they say, questions will be
raised as to whose genome will be considered "normal".
Immense contribution
Meanwhile, Matt Hurles at the Wellcome Trust Sanger Institute in
Cambridge, UK, and colleagues compared genomes from 270 people in four
ethnic groups: Yoruba in Nigeria; European descendants in the US; Han
Chinese in Beijing; and Japanese in Tokyo. They measured the number of
copies of genes by looking at how well chunks of the genomes bonded to
each other.
They found 1447 CNVs, covering about 12% of the human genome. "One of
the real surprises of these results was just how much of our DNA varies
in copy number. We now appreciate the immense contribution of this
phenomenon to genetic differences between individuals," says Hurles.
"Each one of us has a unique pattern of gains and losses of complete
sections of DNA."
"This research paper will change forever the field of human
genetics," says James Lupski at the Baylor College of Medicine in
Houston in the US, an independent CNV expert. Now, when seeking genetic
causes for diseases, scientists will have to look, not just for
mutations, but for CNVs, he says. The new data have been placed in the
public domain to help researchers do this.
Journal reference: Nature Genetics (DOI: 10.1038/ng1921) Nature (vol
444, p 444)
-------------------------------------
Sanger institute is mentioned. Let's look there,
http://www.sanger.ac.uk/humgen/cnv/
And do the web search,
http://www.google.com/search?hl=en&lr=&q=copy+number+variants+cnv&btnG=Search
And add in keyword psoriasis,
http://www.google.com/search?hl=en&lr=&q=copy+number+variants+cnv+psoriasis&btnG=Search
-----------
Here's a good link to get a view of these gene things,
http://www.brainatlas.org/aba/2006/060615/full/nrg1884.shtml
--------------
randall... what if the problem with P genes is a couple of extra
strands?
randall
Since yesterday, more CNV articles are poping up in the news.
Here's that search,
http://news.google.com/news?qt_s=1&tab=gn&ie=UTF-8&scoring=d&q=psoriasis+cnv&btnG=Search+News
----------------
Do you have the judas enzyme, phospholipase A2? And what can
be done to stoP it?
http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-74690.html
[...]
Now, Professor Johansen and her research group have created various
stop molecules that prevent the "Judas enzyme" from sending the
wrong messages to the cell nucleus. By doing so, the inflammatory
reaction can be prevented.
One of these stop molecules was recently tested in mice infected with
psoriasis. The results are more than promising: Every single mouse got
better, in all respects.
In addition, it turned out that a high dosage yielded better effect
than a low dosage.
Medical testing right around the corner
This discovery means that a substantial part of the road to a new type
of medication is history. The next step is testing on humans.
Early next year, the substance will be available as a cream, ready to
be applied on the first test persons. This testing will take place in
France.
-----------------------------------
Getting back to the cnv story and going back in time a few years with
it.
http://www.sciencedaily.com/releases/2004/08/040801230935.htm
Research Reveals Reveals Gains Or Losses Of Large Segments Of DNA In
Healthy People
TORONTO -- Scientists at The Hospital for Sick Children (Sick Kids),
Brigham and Women's Hospital (BWH) and Harvard Medical School (HMS)
have made the unexpected discovery that significant differences can
exist in the overall content of DNA and genes contained in individual
genomes. These findings, which point to possible new explanations for
individual uniqueness as well as why disease develops, are published in
the September 2004 issue of the scientific journal Nature Genetics
(available online August 1, 2004).
"Using new genome scanning technologies, we serendipitously found
stretches of DNA sometimes hundreds of thousands of chemical bases
(nucleotides) long that were present or absent in the genomes of
healthy individuals. These large-scale copy variations, or LCVs,
frequently overlap with genes and could explain why people are
different," said Dr. Stephen Scherer, co-principal investigator of the
study, a Sick Kids senior scientist, and an associate professor in the
Department of Molecular and Medical Genetics at the University of
Toronto.
"At first we were astonished and didn't believe our results because for
years we had been taught that most variation in DNA was limited to very
small changes. Then we heard the Harvard group was making similar
observations and ultimately we combined our data and came to the same
conclusion," added Dr. Scherer.
Early information from the Human Genome Project indicated that the DNA
in the genome of any two individuals is 99.9 per cent identical with
the 0.1 per cent variation arising primarily from some three million
single nucleotide changes scattered amongst the chromosomes. The new
data from the Sick Kids and Harvard groups revealed 255 regions
(comprising more than 0.1 per cent) of the genome where large chunks of
DNA are present in different copy numbers between individuals. Over 50
per cent of these alterations lead to changes in gene numbers and at
least 14 regions overlapped with known sites associated with human
disease.
"Because these newly discovered variants exist in the genomes of
healthy individuals, their presence could lead to subtle differences
affecting physical or behavioural traits by influencing the expression
of specific genes, but they could also predispose to future disease,"
said BWH's Dr. Charles Lee, co-principal investigator and assistant
professor at HMS. "For example, the most common LCV involves amylase
genes. Our study shows that some people may have 10 copies of this gene
while others may have as much as 24 copies of this same gene. It would
be really exciting if we found that an increased copy number of these
genes was associated with increased susceptibility to pancreatic
diseases or cancer. This would allow us to use these LCVs as disease
markers."
The information on identified LCVs has been collated into a publicly
accessible database called the Genome Variation Database
(http://projects.tcag.ca/variation) that will be a valuable resource
for clinical genetic studies. <SNIP>
--------------------------
How do genes efficiently express themselves?
http://www.sciencedaily.com/releases/2004/07/040730090316.htm
Database of genomic variants
http://projects.tcag.ca/variation/
Try a runx search,
http://projects.tcag.ca/variation/search.asp?keyword=runx&source=hg17&table=Locus&filter=&show=table&exactMatch=no
We can search all the p genes with this search engine.
Does it just come down to phospholipase A2?
Certainly we've looked at that a million times in this group.
http://groups.google.com/groups/search?ie=UTF-8&q=psoriasis+phospholipase+A2&qt_s=Search
And once again it brings up questions of the recent linkage of P to
heart disease.
So maybe that research will help with psoriasis? We have to use
resources were
we find them.
Here's a company with a PLA-2 test for heart complications.
------------------------
diaDexus, Inc., a privately held biotechnology company based in South
San Francisco, Calif., is focused on the discovery, development, and
commercialization of clinically valuable, patent-protected diagnostic
products. The company's PLACĀ® test has been cleared for marketing by
the Food and Drug Administration as an aid in predicting risk for
coronary heart disease and ischemic stroke associated with
atherosclerosis. The test measures lipoprotein-associated phospholipase
A2 (Lp-PLA2), a cardiovascular-specific inflammatory enzyme associated
with unstable, rupture-prone plaque-the leading cause of
cardiovascular events. diaDexus also is developing a pipeline of novel
cancer diagnostic tests. For more information, visit www.plactest.com
or www.diaDexus.com.
------------------------
Will that new cream to block the *JUDAS* enzyme pla-2 be a savior for
us?
It's the grail for now, till all those psoriasis genes are mapped out
and dealt with.
And now that this map includes all the cnv's we can understand it
somewhat better.
randall... happy thanksgivings!!!
randall
http://www.medicalnewstoday.com/medicalnews.php?newsid=57334&nfid=nl
Autoimmune Disease Triggered If T Cells Miss A Single Protein Early On
Scientists have discovered that autoimmunity can be triggered in the
thymus, where the immune system's T cells develop, if T cells fail to
recognize just one of the body's thousands of proteins as "self." The
research confirms an emerging view that autoimmunity can start in this
cradle of the immune system, and not only at the sites where autoimmune
diseases emerge, such as the pancreas in the case of type 1 diabetes,
or the joints in rheumatoid arthritis.
The discovery, from a mouse model of a human autoimmune condition,
suggests that effective strategies to treat autoimmune disease should
target not only the "peripheral" sites where autoimmune disease is
active, but also the thymus -- the organ where T cells and
self-proteins, or self-antigens, first interact.
The research was led by investigators at the University of California,
San Francisco (UCSF). It was published online by the Journal of
Experimental Medicine and will appear in the journal's print edition
November 27.
T cell soldiers encounter the body's full array of proteins in the
thymus, and those T cells with receptors that recognize "self"
proteins, or antigens, normally are purged to avoid autoimmune attacks
in the body later on. The new research showed that if just one of the
body's antigens is not recognized as "self," this single failure can
lead to a severe autoimmune disease in the retina.
"The thymus is like a filter," said Mark Anderson, MD, PhD, assistant
professor of medicine at the UCSF Diabetes Center, and senior author of
a scientific paper describing the discovery. "It is removing or pulling
out autoreactive T cells. What this new study shows is if just one
self-antigen is missing as the T cells go through the filter, it looks
like this alone can lead to an autoimmune disease."
"The finding supports the promise of treatments targeting individual
body proteins or antigens since we have shown that a single
self-antigen can trigger disease," he added.
A similar mechanism may be at play involving other autoimmune diseases
such as type 1 diabetes, Anderson said. Immunologists have demonstrated
that insulin is expressed in the thymus - not just in the pancreas.
Studies have shown that people who are protected from diabetes express
high levels of insulin in the thymus, while those who are predisposed
express lower levels of insulin in this organ.
"What we think is that 'more is better' in the thymus," Anderson says.
"If you have more insulin in the thymus, then there is a better chance
that potentially destructive insulin-specific T cells will encounter
insulin as self and be filtered out."
In the thymus, immature T cells display on their surface many thousands
of unique receptors, generated by random gene rearrangements. This
strategy allows the receptors to recognize the tremendous diversity of
invading pathogens. In the process, however, they also develop
receptors that bind to the body's own proteins. These T cells are
normally eliminated, avoiding the plague of autoimmunity.
A clue to how the elimination process is controlled came from previous
work involving a protein in the cell nucleus called Aire (for
autoimmune regulator), which regulates the expression of some 300 to
1,000 antigens in the thymus. Humans and mice lacking the normal Aire
gene suffer from multiple autoimmune diseases including diseases that
target the thyroid, adrenal, ovary, and eye.
In 2002, Anderson, then at Harvard Medical School, and colleagues there
demonstrated that knocking out the Aire gene in the mouse thymus led to
failures of expression of a number of genes in peripheral tissues,
resulting in autoimmune diseases in those tissues -- the first direct
evidence linking gene knockouts in the thymus to autoimmune defects in
body tissues. The study, however, did not link a specific organ
autoimmune attack with a specific protein missing in the thymus.
In the new study, the researchers carried out a detailed analysis of
the autoimmune attack that is directed against the eye in
Aire-deficient mice. What the team found was that the immune system was
mainly targeting a single eye protein called IRBP despite the fact that
several eye-specific proteins were missing in the thymus of Aire
knockout mice. The team then went on to show that IRBP was expressed in
the thymus under the control of Aire and that knockout mice lacking the
IRBP protein were protected from the disease because they don't express
the protein that the immune system is targeting.
In a key, final part of the new study, Anderson and his colleagues
showed that if mice without a thymus gland - so-called "nude" mice -
received a normal thymus lacking only IRBP, they developed the
autoimmune eye disease. The autoimmune attack occurred even though the
mice had normally functioning IRBP in their retinas. The final finding
demonstrated that failure of T cells in the thymus to recognize IRBP as
a self-protein was sufficient to cause the autoimmune disorder in the
retina.
The scientists hope that better understanding of interactions in the
thymus can lead to earlier, more effective treatment of autoimmune
diseases.
"When we see autoimmune disease in the clinic, we are usually looking
at it in a relatively late stage. Tissue is already damaged, antigen
expression is ramped up and the immune response is spreading to other
self-antigens," Anderson said. "If we can also train our focus on the
thymus, where we know at least some of the autoimmune disease is
triggered, we may be able to determine just what self-antigens are
important and shut down the autoimmune process targeting those self
-antigens."
The team is collaborating with Jeffrey Bluestone, PhD, director of the
UCSF Diabetes Center, in preclinical studies to see if T cell
autoimmune attacks on IRBP can be modulated to prevent the autoimmune
eye disease.
###
Lead author is Jason DeVoss, PhD, a postdoctoral scientist in
Anderson's laboratory.
Co-authors include Lawrence Fong, MD, PhD, UCSF assistant professor of
hematology and oncology; Yafei Hou, PhD, a postdoc in Fong's lab; Wen
Lu, BS, and Kellsey Johannes, BA, both research assistants in
Anderson's lab.
Also: Gregory Liou, PhD, associate professor of ophthalmology at the
Medical College of Georgia; Howard Chang, MD, PhD, assistant professor
dermatology at Stanford University School of Medicine; John Rinn, PhD,
a postdoctoral scientist in Chang's lab; and Rachel Caspi, PhD, section
head, Laboratory of Immunology, National Eye Institute.
The research is supported in part by the National Institutes of Health.
UCSF is a leading university that advances health worldwide by
conducting advanced biomedical research, educating graduate students in
the life sciences and health professions, and providing complex patient
care.
Contact: Wallace Ravven
University of California - San Francisco
----------------------
well? We know the triggers and the fuel.
If only to prevent one will we be saved for ever?
randall...
randall
On Nov 28, 12:21 pm, "randall" <ranhu...@aol.com> wrote:
> Hi,
>
> http://www.medicalnewstoday.com/medicalnews.php?newsid=57334&nfid=nl
>
> Autoimmune Disease Triggered If T Cells Miss A Single Protein Early On
>
<sniP>
I found the pubmed abstract for the previous article.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17116738&query_hl=11&itool=pubmed_docsum
Spontaneous autoimmunity prevented by thymic expression of a single
self-antigen.
Devoss J, Hou Y, Johannes K, Lu W, Liou GI, Rinn J, Chang H, Caspi R,
Fong L, Anderson MS.
Diabetes Center and 2Department of Medicine, University of California,
San Francisco, San Francisco, CA 94143.
The expression of self-antigen in the thymus is believed to be
responsible for the deletion of autoreactive T lymphocytes, a critical
process in the maintenance of unresponsiveness to self. The Autoimmune
regulator (Aire) gene, which is defective in the disorder autoimmune
polyglandular syndrome type 1, has been shown to promote the thymic
expression of self-antigens. A clear link, however, between specific
thymic self-antigens and a single autoimmune phenotype in this model
has been lacking. We show that autoimmune eye disease in aire-deficient
mice develops as a result of loss of thymic expression of a single eye
antigen, interphotoreceptor retinoid-binding protein (IRBP). In
addition, lack of IRBP expression solely in the thymus, even in the
presence of aire expression, is sufficient to trigger spontaneous
eye-specific autoimmunity. These results suggest that failure of thymic
expression of selective single self-antigens can be sufficient to cause
organ-specific autoimmune disease, even in otherwise self-tolerant
individuals.
PMID: 17116738
-----------------------------
Finding an antigen is a grail moment for sure. Hope this research pans
out for us.
Once again, coming up next, Autism and psoriasis connections. If
resarch in to some
other autoimmune condition sheds light on P gene, then so be it.
We have to take the help from any direction.
http://www.upi.com/ConsumerHealthDaily/view.php?StoryID=20061126-083754-1524r
Ped Med: The biological factor in autism
By LIDIA WASOWICZ
UPI Senior Science Writer
SAN FRANCISCO, Nov. 28 (UPI) -- Scientists trying to dig up the roots
of autism are unearthing mounting evidence of the immune system's
involvement in the intractable disorder.
Scientific hints that the body's disease-fighting mechanisms play a
role in autism first surfaced in 1986, researchers said.
However, for the most part, these studies were small and the results
inconclusive so that what now appears a logical concept didn't catch on
until more recently, said David Amaral, professor of psychiatry and
behavioral sciences at the University of California, Davis, School of
Medicine and Medical Center and M.I.N.D. research director.
"You cannot have a normal neurodevelopment without having a normal
immune system," said Judy Van de Water, an immunology specialist at the
UC Davis Center for Children's Environmental Health.
[...]
Although still preliminary, results of one study -- of 88,000 babies
born between 1995 and 1999 in Northern California -- hint at an
increased risk of autism in the offspring of mothers with psoriasis, a
chronic condition that runs in families.
Some 3 million American women of child-bearing age have the disorder
marked by itchy, scaly, inflamed skin on the elbows, knees, back and/or
scalp, according to the patient advocacy group Psoriasis Cure Now!
The early findings also indicate expectant mothers suffering from
asthma and allergies -- particularly during the second trimester -- may
face double the typical risk of giving birth to a child with autism.
However, the presence during pregnancy of 45 other autoimmune diseases
that turn the body against itself -- including rheumatoid arthritis,
type 1 diabetes, rheumatic fever, certain heart complications, lupus
and multiple sclerosis -- appear to have no bearing on the baby's
autism status, the study authors reported.
These maladies are under scrutiny because they affect primarily women
-- who account for 78 percent of all cases -- and because chemicals
produced in response to their presence often are found at high levels
in the bloodstream of autistic children.
That would suggest a possible link between autism and pre-birth
exposure to an autoimmune ailment, scientists said.
The authors speculate a common genetic cause may underlie such
conditions as asthma and autism. Or, because the mother's illness was
frequently diagnosed in the second trimester of pregnancy, the flare-up
may have triggered her immune system to produce more inflammatory
cytokines, which, in turn, might have disrupted brain development in
the fetus, the researchers proposed.
(Note: In this multi-part installment, based on dozens of reports,
conferences and interviews, Ped Med is keeping on eye on autism, taking
a backward glance at its history and surrounding controversies, facing
facts revealed by research and looking forward to treatment
enhancements and expansions. Wasowicz is the author of the forthcoming
book, "Suffer the Child: How the American Healthcare System Is Failing
Our Future," to be published by Capital Books.)
Next: Some autism study results point in genetic directions
-----------------------
Have you got a food allergy? Eat it.
http://news.biocompare.com/newsstory.asp?id=160937
Children who were allergic to eggs were able to essentially overcome
their allergy by gradually consuming increased quantities of eggs over
time, researchers at Duke University Medical Center and the University
of Arkansas for Medical Sciences have found in a small pilot study
"Participants who took a daily dose of egg product over the two-year
study period were able to build up their bodies' resistance to the
point where most of them could eat two scrambled eggs without a
reaction," said A. Wesley Burks, M.D., chief of Duke's Division of
Allergy and Immunology and a senior member of the research team. "Egg
allergies cause a significant decrease in quality of life for many
people, so this study is exciting in that it brings us a step closer to
being able to offer a meaningful therapy for these people."
Egg allergy is one of the most common food allergies among children in
the United States, Burks said. Just how many children are allergic to
eggs is unclear, but the National Institute of Allergy and Infectious
Diseases estimates that 6 percent to 8 percent of children have some
type of food allergy. Most children outgrow egg allergy by age 5, but
some people remain allergic for a lifetime.
The findings are reported in an advance online edition of the Journal
of Allergy and Clinical Immunology and will appear in the journal's
January 2007 print edition.
The study was funded by the National Institutes of Health and the two
universities.
The study is the first in a series of studies on food allergy
"desensitization" that are under way at Duke and the University of
Arkansas. The goal, Burks said, is to offer food allergy sufferers
protection from accidental ingestion of items that provoke reactions
and, eventually, to induce complete or near-complete tolerance to those
items.
Burks and his colleagues modeled the study on a commonly used method
for treating seasonal allergy sufferers to alleviate symptoms. In this
approach, called immunotherapy, physicians give patients shots
containing small amounts of the troublesome allergen in an effort to
build their tolerance to it. The therapy works on a cellular level to
alter specific immune system cells, called lymphocytes, that play a
part in orchestrating allergic reactions and to increase the immune
system's production of antibodies that attack and neutralize allergens,
Burks said.
The seven subjects in the study, who ranged from 1 to 7 years of age,
had a history of allergic reactions, including hives, wheezing and
vomiting, when they consumed eggs or egg products. For safety's sake,
none of the children enrolled had previously experienced a
life-threatening allergic reaction, Burks said. As an extra precaution,
the subjects received a supply of epinephrine, which is commonly used
to treat breathing problems that can occur with food allergy.
Instead of receiving shots, as seasonal allergy sufferers do, the
subjects were given small doses of powdered egg orally, mixed in food.
"We started the subjects with a very small concentration of egg product
-- the equivalent of less than one-thousandth of an egg -- and then we
increased the dose every 30 minutes for eight hours in order to
determine the highest dose that each subject could tolerate," Burks
said.
The subjects consumed the first doses in the study clinic. The
researchers then gave the children's parents or caregivers a supply of
egg product, allocated into the tolerated doses, which the subjects
consumed daily at home, mixed with other foods.
The children returned to the clinic every two weeks. At each visit, the
researchers increased the subjects' dosages until they reached the
equivalent of one-tenth of an egg, Burks said. The children then
continued to take this "maintenance dose" daily for the duration of the
study.
Over time, the children showed both an increase in tolerance to eggs
and a decrease in the severity of their allergic reactions, Burks said.
At the end of the study period, most of the children could tolerate two
scrambled eggs with no adverse reactions.
The researchers now are conducting two follow-up food allergy
desensitization studies, Burks said. In one study, subjects receive
higher doses of egg to see if this will further reduce their
sensitivity or even neutralize the allergy altogether.
The second study focuses on children who are allergic to peanuts, to
see if the desensitization approach can build their tolerance and
decrease the severity of their reactions. Peanut allergy, which can be
life-threatening, affects approximately 1 percent of children under age
5, and its incidence has been on the rise over the past 15 years,
according to Burks. Studies have shown that about 20 percent of
children with egg or milk allergy will go on to develop a peanut
allergy.
Other members of the research team were Ariana Buchanan, Todd Green,
Pamela Steele, Laurent Pons and Laurie Lee of Duke and Amy Scurlock,
Lynn Christie, Karen Althage and Rick Helm of the University of
Arkansas
--------------------------------
randall...
randall
randall wrote:
> Hi,
>
>
> Since yesterday, more CNV articles are poping up in the news.
>
>
> Here's that search,
> http://news.google.com/news?qt_s=1&tab=gn&ie=UTF-8&scoring=d&q=psoriasis+cnv&btnG=Search+News
>
> ----------------
>
> Do you have the judas enzyme, phospholipase A2? And what can
> be done to stoP it?
> http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-74690.html
>
> [...]
> Now, Professor Johansen and her research group have created various
> stop molecules that prevent the "Judas enzyme" from sending the
> wrong messages to the cell nucleus. By doing so, the inflammatory
> reaction can be prevented.
>
> One of these stop molecules was recently tested in mice infected with
> psoriasis. The results are more than promising: Every single mouse got
> better, in all respects.
>
> In addition, it turned out that a high dosage yielded better effect
> than a low dosage.
>
> Medical testing right around the corner
>
> This discovery means that a substantial part of the road to a new type
> of medication is history. The next step is testing on humans.
>
This is an article from a few years back that will indoctrinate the
layman to the autoimmune condition.
Not so much from the the Th1/Th2 perspective, but close enough to get
an idea.
(Th1 refers to T helper 1 cells and Th2 is T helper 2 cells)
By Judy Moeckel
They tend to strike people in early adulthood, in the "prime" of their
lives. They strike women far more often than men. Researchers don't yet
know exactly what causes autoimmune diseases, but they are moving in
that direction.
Cindy Harward of Durham, who has lived with lupus disease for many
years, likens the autoimmune reaction to the body "rejecting itself."
The immune system is overactive, she says, the opposite of what happens
with AIDS, where the immune system is suppressed or nonfunctional.
(randall note: autoimmune is Th1 and aids/cancer are Th2 conditions)
The website of the National Institute of Allergy and Infectious
Diseases, part of the National Institutes of Health
(www.niaid.nih.gov/publications/autoimmune) states:
"The word "auto" is the Greek word for self. The immune system is a
complicated network of cells and cell components (called molecules)
that normally work to defend the body and eliminate infections caused
by bacteria, viruses and other invading microbes. If a person has an
autoimmune disease, the immune system mistakenly attacks self,
targeting the cells, tissues and organs of a person's own body. A
collection of immune system cells and molecules at a target site is
broadly referred to as inflammation."
The term "autoimmune disease" encompasses a large and mind-boggling
variety of conditions, including multiple sclerosis, Crohn's disease (a
serious gastrointestinal disorder), rheumatoid arthritis; systemic
lupus erythematosus (commonly called lupus); myasthenia gravis; certain
forms of asthma, diabetes, dermatitis and _____psoriasis____,
hepatitis, anemia
and cirrhosis and Addison's disease, to name but a few.
Besides providing a laundry list of disorders believed to be caused by
the body preying upon itself, the Merck Manual of General Medicine has
a category for "other inflammatory, granulomatous, degenerative and
atrophic disorders" for which there is "no reasonable alternative
explanation." This would include, for example, fibromyalgia, which
involves muscular pain and tenderness, often both acute and diffuse,
but where there is no clear evidence of tissue damage.
(or, as in my other post today- P News. Seronegative conditions like
PsA are Th1- autoimmune)
Autoimmune diseases often follow a pattern of disease "flare up" or
activity, followed by "remission" or inactivity, when symptoms
diminish. Damage (to tissues, joints, etc.) done during flare ups
usually persists, and the disease is rarely if ever "cured."
How do autoimmune diseases work? Daniel Doty of Durham, who was
Chairperson of the Board of Directors of the Connecticut chapter of the
National Multiple Sclerosis Society from 2001 to 2004 and is still
actively involved in the organization, says a genetic "marker" for MS
has not been discovered-yet-but it appears some people may be
predisposed by family history.
According to the NIAID website, the genes people inherit contribute to
their susceptibility for developing an autoimmune disease. Diseases
such as psoriasis can occur among several members of the same family,
suggesting that a specific gene or set of genes predisposes a family
member to the condition. They note that, "individual family members
with autoimmune diseases may inherit and share a set of abnormal genes,
although they may develop different autoimmune diseases."
Cindy Harward says a marker is "suspected' in lupus also, but there
needs to be a ___trigger____ such as medications, environmental
factors, or a
fever (strep works for P), before the disease manifests itself. Sheldon
Paul Blau, MD,
author of Living with Lupus (1993), agrees that there are "suggestions
of...subtle genetic factors" with lupus, and states that autoimmune
diseases like lupus are NOT contagious, nor are they related to
diseases such as AIDS or cancer.
(Duh: Psoriasis isn't contagious either!)
"While there may be an infectious agent or agents involved in lupus, it
is not an agent that can carry the condition from one person to
another, like the measles virus."
Nor are diseases such as lupus passed on through sexual activity; in
the late 1970's, Blau says, before the AIDS virus was identified, it
was rumored that "permissive sexual mores" were causing the spread of
lupus disease. Sadly, the rumor mill hurt people with both diseases.
Cindy Harward was diagnosed with lupus about 32 years ago. While in
college (she was a physical education major), she was working at a
playground, and suddenly broke out in a bad rash. The first
dermatologist she went to thought it was an allergy to the sun, and
recommended that she use sunscreen and avoid the sun. Harward also had
joint pain, one of the symptoms of lupus, but did not think to mention
it.
Eventually she saw another dermatologist, who took one look at her
rash, heard about her joint pain, and suspected lupus. Blood tests
confirmed the diagnosis. Harward says diagnosis is not always this
clear-cut.
Lupus can impact almost any part of the body, including the central and
peripheral nervous system, the heart and lungs, kidneys,
musculoskeletal structures, gastrointestinal and reproductive systems,
blood (usually clotting problems), and skin (manifested as extreme
sensitivity to the sun, a "butterfly" rash on the face, and/or
lesions). Most people experience symptoms in only a few of the body's
organs.
Across the years since her lupus was diagnosed, Harward has adjusted
her career to meet her changing physical condition. Her first move was
to change from physical education to health education. Eventually, she
obtained a Master's degree in adaptive physical education. "I loved it,
but the demands were too great," she says. She moved into consulting
with schools and businesses, including the Wheeler Clinic in
Plainville.
Extreme fatigue has been an ongoing problem, as have the ongoing
effects of tissue damage, which affects her joints and connective
tissues. Harward's ligaments and tendons rupture easily, causing her to
need many surgeries over the years. One time, she says, she was simply
picking up a big of oranges and ended up severing a tendon, as if it
were "spaghetti." These connective tissue problems have a domino
effect, resulting in orthopedic damage to bones and joints. Harward
suspects that the medications she has taken over the years, including
prednisone, may have contributed to the damage.
Despite the challenges, Harward maintains a positive outlook. "I get
into trouble because I push it," she says. I'm not the type to get
this!" An energetic and outgoing person, she knows she has to plan her
time carefully. For the past eight years, she has worked at Ameritage
Realty on Route 66 in Middlefield. The flexibility of the job suits her
physical needs, and she is very happy there.
Strong support from family and friends has helped Harward cope
successfully with lupus. Besides her family, she says that the "man in
her life"-Lou Torelli-has been a "rock" for her for nearly 25
years.
(You go girl! Hold on to the rock. LOL)
Several times a year, she visits classes at the medical school at the
University of Connecticut, putting a human face on the disease of
lupus. She notes that October is Lupus Awareness Month; the annual
Lupus Walkathon, sponsored by the Connecticut Chapter of the Lupus
Foundation of America, will take place on September 25, at the MDC
Reservoir on Farmington Avenue in West Hartford.
The chapter also will sponsor a golf tournament on May 21, and on April
1, the foundation will sponsor Lupus Alert Day; their slogan is "Don't
Be Fooled by Lupus."
For more information on all these events, go to www.lupusct.org, e-mail
c...@aol.com, or call 860-953-0387; toll free 800-699-6967. Funds
donated go to increase public awareness of the disease, and to fund
basic research.
A wealth of information is available at the Lupus Foundation of
America's website www.lupus.org.
As an article in the newsletter of the Maryland Lupus Foundation says,
"living with lupus can feel, at times, like an endless tightrope walk
on a bad day at the circus." But, as the article's author Jeri Falk
says, "just as we each have our own unique losses, we also have our own
special ways of coping, of regaining our balance, of surviving."
Cindy Harward knows her lupus won't go away, but she says she is
prepared to face the upcoming chapters in her life. Her outlook is
positive, which is possibly the best medicine around.
Next time: multiple sclerosis, research in autoimmune diseases and
resources.
-----------------------------------
Why not look at gut and autoimmune genes again?
OK, i'm game.
Card15/NOD2
http://ghr.nlm.nih.gov/gene=card15;jsessionid=7A19984D0625A0FAAB8180D89F318722
http://www.iir.suite.dk/IIR/13auto/CrCARD15.htm
Blau, psoriasis, crohn's
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=122098&tools=bot
[...]
the Blau syndrome (MIM 186580), an autosomal dominant granulomatous
disease of childhood, is a rare familial granulomatous disease [1].
Affected individuals typically display one or more of the following
granulomatous inflammations that have variable age-at-onset: acute
anterior uveitis, arthritis, and skin rash. The phenotype of the Blau
syndrome resembles another multisystem granulomatous disorder, Crohn's
disease (MIM 266600), and another autoimmune disease, psoriasis (MIM
177900). These three inflammatory diseases not only share phenotypic
features, but a subset of putative risk loci mapped to an overlapping
region on chromosome 16. Of the several putative susceptibility loci
for Crohn's disease [2-7] and psoriasis [8], the Crohn's locus on 16q
between markers D16S409 and D16S419 (56.1-65.6 cM from p-terminus)
[5] and the psoriasis locus on 16q near D16S3110 [8] overlap with the
locus for the Blau syndrome. Interestingly, another autoimmune disease
ankylosing spondylitis (MIM 106300), also maps to chromosome 16q,
however, it appears to map telomeric to the Blau syndrome interval
[9,10]. <sniP>
-------------------
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&dispmax=100&term=%20blau+card15
-----------
whooPs, no time left. Must go live some. <w>
randall... the liver!