Infection?
manfred
http://americancanceradvocates.com/Autoimune_Discoveries.html
AFTER RESEARCHING FOR SIX YEARS WE HAVE FOUND ALL THE ANSWERS AND ARE
PUBLISHING OUR AMAZING RESULTS:
THE MOST CONVINCING ARGUMENT TO DATE! AUTOIMMUNE DISORDERS ARE VIRAL
INFECTIONS, (With very few exceptions.)
WHAT IS THE COMMON INGREDIENT?
So what is this hyped- up common ingredient?
It is most certainly linked to the a dozen most touted alternative
treatments across the globe!!
What is the link? Ok I will tell you:
Oxygen!!!
Continued at:
http://americancanceradvocates.com/Therapeutic_Substances.html
Ok---Maybe
If it is a lingering infection of some sort here is another approach:
MMS is a stabilized oxygen formulation that is a 28% solution of
Sodium Chlorite in distilled water. When ordinary white vinegar is
added to a few drops of MMS, Chlorine Dioxide is created and when
ingested, it kills virtually every known pathogen, including bacteria,
viruses, fungi, molds, and yeasts.
While first developed to address Malaria in Africa, it has now been
shown to address any disease condition that is directly or indirectly
related to pathogens. There is documentation of over 75,000 cases of
Malaria being overcome in Africa. Often in as little as 4 hours all
symptoms are gone and the victim is tested clear of Malaria. It is now
known that MMS can be used to overcome the symptoms of AIDS, Hepatitis
A,B&C, Typhoid, most cancers, herpes, pneumonia, food poisoning,
tuberculosis, asthma, colds, flu and a host of other conditions. Even
conditions not directly related to pathogens seem to be helped due to
the huge boost to the body's immune system, i.e., macular
degeneration, allergies, lupus, inflammatory bowel disorders,
diabetes, snake bites and fibromyalgia. Please note that MMS doesn't
cure anything, but rather it allows our body to heal itself.
Listen at
http://www.webtalkradio.net/content/view/32/33/
Part 1 of his book is at
Cruiser
Fred,
The first link does not work.
Did you see these responses, that I posted a couple weeks ago?
------------------------
It is my opinion, after extensive research, that hypoxia is the
underlying cause of psoriais, in people genetically predisposed to
psoriasis. My problem has been identifying the cause of the hypoxia.
eNOS is implicated, with potential implications of upstream chemical
reactions involving BH4, Inositol, cGMP, and acetylcholine.
Acetylcholine is a signalling molecule, that stimulates the
epithellial G receptors, stimulating cGMP, which then cascades to
inositol and BH4. Normally eNOS, is bound in the epithelial membrane,
and is inactive in the bound state. This chemical cascade liberates
eNOS from the epithelial membrane so that it becomes active. eNOS is
epithelial nitric oxide synthase. It is an enzyme that makes nitric
oxide from arginine. Nitric oxide dilates blood vessels, an this
provides more oxygen to tissues.
This is the exact same chemical chain where Viagra works, bypassing
the G receptor signalling.
As Fred pointed out, Dr. Paul has posted an article and is lecturing
that this process can go wrong, such that it produces ONOO, which is
a
powerful vasal constrictor.
Dr. Paul advocates various anti-oxidant supplements, which he will be
happy to sell you.
What he does not mention is all the research that indicates Folic
Acid
will mitigate the problem. The way folic acid does this is not
completely understood, but it appears to be related to the BH4 part
of
the process. Folic acid may recycle BH4, or it may mimic BH4.
------------------------
OK, I found something on oral dosage.
http://www.bh4.org/pdf/das.pdf
"It is also interesting to note that oral folic acid supplementation
(10 mg/d) to healthy human volunteers not only restored NO synthesis
to normal but also prevented nitrate tolerance to continuous
treatment
with nitroglycerin, possibly by restoring or stimulating endogenous
regeneration of H4B.29"
By H4B they mean BH4, which I mention above.
http://ves.sagepub.com/cgi/content/abstract/41/4/339
"Patients were then treated with 10 mg folic acid, 100 mg vitamin B6,
and 1 mg vitamin B12 orally once a day for 6 months."
I have also seen much reference to 15 mg folic acid per day dosing.
Please note that the dose is in milligrams and not micrograms.
Standard doses for prepared caps or tablets of folic acid are
typically either 400 micrograms or 1 milligram.
You need to take ten to fifteen 1 mg capsules or tablets each day of
folic acid.
Higly recommended to also take the 100 mg vitamin B6, and 1 mg
vitamin
B12.
cruiser
randall
> http://americancanceradvocates.com/Autoimune_Discoveries.html
Same thing happened to me as cruiser. The link doesn't work.
So, I went to the next link down and found the autoimmune page on
discoveries.
What they bring up is HIAP-1 found at Tulane by author, GARRY.
So I went and looked at his work on pubmed: (129 hits)
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Garry%20RF%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus
There are 11 hits for keywords HIAP (human intracisternal A-type
retroviral particle) and author Garry, the last being in 2005.
And here is Garry's most recent HIAP post from 2005:
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16276517&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Involvement of human intracisternal A-type retroviral particles in
autoimmunity.
Sander DM, Szabo S, Gallaher WR, Deas JE, Thompson JJ, Cao Y, Luo-
Zhang H, Liu LG, Colmegna I, Koehler J, Espinoza LR, Alexander SS,
Hart DJ, Tom DM, Fermin CD, Jaspan JJ, Kulakosky PC, Tenenbaum SA,
Wilson RB, Garry RF.
Graduate Program in Molecular and Cellular Biology and Department of
Microbiology and Immunology, Tulane University Health Sciences Center,
New Orleans, Louisiana, USA. dmsa...@sanderassociates.com
Prior studies have linked retroviruses to various arthropathies and
autoimmune diseases. Sjögren's syndrome (SS), a systemic autoimmune
disease, is characterized by aggressive infiltration of lymphocytes
into the salivary and lacrimal glands, resulting in destruction of the
glands and dry mouth and eyes (sicca syndrome). The infiltrating
lymphocytes in SS may become overtly malignant, and thus, the
incidence of lymphoma is greatly increased in SS patients. A human
intracisternal A-type retroviral particle type I (HIAP-I) has been
isolated from persons with SS. HIAP-I shares a limited number of
antigenic epitopes with human immunodeficiency virus (HIV), but is
distinguishable from HIV by morphological, physical, and biochemical
criteria. A substantial majority of patients with SS or systemic lupus
erythematosus (SLE) have serum antibodies to the proteins of this
human retrovirus. Fewer than 3% of the normal blood donor population
have antibodies to any HIAP-associated proteins. A second type of a
human intracisternal A-type retrovirus, HIAP-II, was detected in a
subset of patients with idiopathic CD4 lymphocytopenia (ICL), an AIDS-
like immunodeficiency disease. Most HIAP-II positive ICL patients were
also antinuclear antibody positive. Reviewed here are additional
studies from several laboratories suggesting that HIAP or related
viruses may be involved in SLE and other autoimmune conditions.
Additionally, results of comprehensive surveys of autoimmune patients
to determine seroreactivity to HIAP, and other human retroviruses,
including HIV and human T-lymphotropic virus type I, are reported.
2005 Wiley-Liss, Inc.
PMID: 16276517
Manfred, this is a fast moving field. Did they change the name or just
loose interest in HIAP?
Here's an abstract from Dec/2006 and Garry has moved on to HERV's for
Ai conditions.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17118296&ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Role of endogenous retroviruses in autoimmune diseases.
Colmegna I, Garry RF.
Section of Rheumatology, Department of Medicine, Louisiana State
University Health Sciences Center, 2020 Gravier Street, New Orleans,
LA 70112, USA.
Molecular epidemiologic proof that HERVs and other retroelements are
involved in autoimmunity or other disorders is complicated by their
large numbers in the human genome. As discussed, most HERVs are no
longer functional or active because of the accumulation of mutations,
frameshifts, and deletions. Detection or quantification of HERV
transcripts that may be pathologically involved in a particular
autoimmune disease thus is often compromised by the presence in great
excess of related, but nonfunctional, RNA. This phenomenon should not
deter active work in the field, although it will require development
of improved methods to discriminate accurately between closely related
RNA transcripts. Development of improved immunologic methods to
precisely identify epitopes on autoantigens or rare self-reactive T-
cell clones may further implicate HERVs and the other repetitive
elements in regulation of the immune system in health and disease.
PMID: 17118296
He's also big on Small interfering RNA (NOV/2006) to cure viral
conditions. Which is an admission
to a genetic paradigm in autoimmune conditions iirc.
That page on autoimmune discoveries is a wish list and oversimplified
as the
person who wrote it is the same as your average psoriatic. He wants a
CURE now....
>
> AFTER RESEARCHING FOR SIX YEARS WE HAVE FOUND ALL THE ANSWERS AND ARE
> PUBLISHING OUR AMAZING RESULTS:
How long have they been working on the Ai called psoriasis? Longer
then six years. LOL
>
> THE MOST CONVINCING ARGUMENT TO DATE! AUTOIMMUNE DISORDERS ARE VIRAL
> INFECTIONS, (With very few exceptions.)
WRONG.... hey I can use caPitals as well. LOL
>From the most CURRENT research, psoriasis in my mind is still a
genetic screw uP....
Didn't I use the shegoi product and prove this myself? LOL
http://groups.google.com/groups/search?qt_s=1&q=shegoi+herpes+psoriasis
Look at the fourth post down. Kathleen leslie says it cures Aids, MS,
cancer, psoriasis etc.
>
> WHAT IS THE COMMON INGREDIENT?
>
> So what is this hyped- up common ingredient?
> It is most certainly linked to the a dozen most touted alternative
> treatments across the globe!!
> What is the link? Ok I will tell you:
> Oxygen!!!
So? What? We stoP breathing? LOL, LOL..... this page is nonsense.
>
> Continued at:http://americancanceradvocates.com/Therapeutic_Substances.html
This link can be used to get to the autoimmune page which is mostly
pure nonsense.
So much so, they've most likely inactivated the link to get to it
simply. LOL <w>
OK, I found this at the end of the page.
>From autoimmune discovery page::
----------------
While we rebuild this website contact us
PATIENTA...@YAHOO.COM
480-285-6716
------------------
Why don't you call this guy to find out how big a donation he needs?
LOL
Maybe it's Uwe? LOL
Why did he stop curing everyone in the world? Must not have worked
out? LOL
>
> Ok---Maybe
> If it is a lingering infection of some sort here is another approach:
>
> MMS is a stabilized oxygen formulation that is a 28% solution of
> Sodium Chlorite in distilled water. When ordinary white vinegar is
> added to a few drops of MMS, Chlorine Dioxide is created and when
> ingested, it kills virtually every known pathogen, including bacteria,
> viruses, fungi, molds, and yeasts.
Nonsense. Drinking bleach with vinegar or drinking hydrogen peroxide
are all quackery. Using it topically may help for NON autoimmune
conditions.
Certainly Th2 skin conditions with real bacteria etc are a target for
diluted
TOPICAL preparations.
Yet some psoriatic folks swear by drinking apple vinegar each day. I
wouldn't
think that any bleach ( a few drops) would make it very far past the
acid in your stomach.
>
> While first developed to address Malaria in Africa, it has now been
> shown to address any disease condition that is directly or indirectly
> related to pathogens.
They should go back to DDT and save millions of lives.
Doesn't Bill GAtes support foundations to save poor people with
cheap meds? I can find them if you wish?
<sniP>
Lets talk turkey Manfred.
You had a great post recently. Tonilast from Larry Fielder's website?
Why mess it uP? LOL
--------------------------------------------------------
Let's go crazy with this weeks recent autoimmune news.
REmember all the hooPLA over tryptophan and psoriasis?
Some sites said never eat any of the trypto stuff yada yada yada...
Whats the truth about Tryptophan???
Well.... It is a constituent in Th1 (autoimmune aka- Ai) and Th2
(cancer et al) conditions.
New facts for tryptophan and Th2....are here today.
And not from some freak with a page under construction.
We're talking real scientists and not some simple minded explanation
on
a website that says STOP EATING TRYPTOPHAN IT WILL MAKE
PSORIASIS...LOL
http://news.biocompare.com/newsstory.asp?id=197008 ;
Scientists Discover How Cancer May Take Hold
9/24/2007
Source: Carnegie Institution
A team, led by researchers at the Carnegie Institution,* has found a
key biochemical cycle that suppresses the immune response, thereby
allowing cancer cells to multiply unabated. The research shows how the
biomolecules responsible for healthy T-cells, the body's first
defenders against hostile invaders, are quashed, permitting the
invading cancer to spread. The same cycle could also be involved in
autoimmune diseases such as multiple sclerosis. The work is published
in the September 25, 2007, issue of PLoS Biology.
The scientists used special molecular "nanosensors" for the work. "We
used a technique called fluorescence resonance energy transfer, or
FRET, to monitor the levels of, tryptophan, one of the essential amino
acids human cells need for viability," explained lead author Thijs
Kaper. "Humans get tryptophan from foods such as grains, legumes,
fruits, and meat. Tryptophan is essential for normal growth and
development in children and nitrogen balance in adults. T-cells also
depend on it for their immune response after invading cells have been
recognized. If they don't get enough tryptophan, the T-cells die and
the invaders remain undetected."
The scientists looked at the chemical transformations that tryptophan
undergoes as it is processed in live human cancer cells. When
tryptophan is broken down in the cancer cells, an enzyme (dubbed IDO)
forms molecules called kynurenines. This reduces the concentration of
tryptophan in the local tissues and starves T-cells for tryptophan. A
key finding of the research was that a transporter protein (LAT1),
present in certain types of cancer cells, exchanges tryptophan from
the outside of the cell with kynurenine inside the cell, resulting in
an excess of kynurenine in the body fluids, which is toxic to T-cells.
"It's double trouble for T-cells," remarked Wolf Frommer. "Not only do
they starve from lack of tryptophan in their surroundings, but it is
replaced by the toxic kynurenines, which wipes T-cells out."
The scientists think that this cycle may be also be involved in cells
involved in certain autoimmune diseases. In these cases the cells may
not be able to take up or convert enough tryptophan. Without enough of
the amino acid or the IDO enzyme to convert tryptophan, the cells
cannot produce enough kynurenine. Lacking kynurenine, the body's own T-
cells cannot be kept in check, so they rebel and attack the body.
The FRET system detects metabolites such as sugars and amino acids
using a biosensor tag. A protein is genetically fused to tags at
opposite ends of a molecule. The tags are made from different colors
of the jellyfish green fluorescent protein (GFP). When a metabolite
binds to the biosensor, it changes the shape of the sensor's backbone,
altering the position of the fluorescent tags. When a specific
wavelength of light activates one tag, it fluoresces. When the
metabolite causes the tags to move close together, the other tag will
also fluoresce-resonating like a tuning fork. This system allows the
scientists to visually track the location and concentration of certain
biochemicals.
"Our FRET technology with the novel tryptophan nanosensor has an added
bonus," said Thijs. "It can be used to identify new drugs that could
reduce the ability of cancer cells to uptake tryptophan or their
ability to degrade it. We believe that this technology could be a huge
boost to cancer treatment."
==============
Well? We know now or can guess that we don't have to much toxic
kynurenines?
CAn't we?
But, and this is a big one, do psoriatics have "enough of the amino
acid or the IDO enzyme to convert tryptophan, the cells cannot produce
enough kynurenine. Lacking kynurenine, the body's own T-cells cannot
be kept in check, so they rebel and attack the body."
To much to little? Not enough time to figure it out. LOL
Will drinking apple vinergar and or white wine vinegar help? And how
much bleach do we add to this preparation? LOL.... please don't try
this.
This is humor on my part.....
But, but, but.... don't we have to much IFN?
Yes we do.
So?
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17873497&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Interferon-alpha Influences Tryptophan Metabolism without Inducing
Psychiatric Side Effects.
Bannink M, Fekkes D, Van Gool AR, Kruit WH, Sleijfer S, van der Holt
B, Eggermont AM, Stoter G, Hengeveld MW.
Department of Psychiatry, Erasmus Medical Center - Daniel den Hoed
Cancer Center, Rotterdam, The Netherlands.
Background: Interferon-alpha (IFN-alpha) treatment is often associated
with psychiatric side effects and has been found to lower the amount
of tryptophan (TRP) available to the brain. The alterations in
tryptophan metabolism might underlie the psychiatric side effects
during treatment with IFN-alpha. Methods: In this study, 43 oncology
patients treated with IFN-alpha were included. In order to study de
novo depressions, depressed patients at baseline were excluded.
Psychiatric evaluation comprising clinical judgment combined with a
structured psychiatric interview and observer-based and self-report
rating scales was performed at baseline and at 4 weeks, 8 weeks and 6
months after the start of treatment with IFN-alpha, and in the case of
emerging psychopathology. Blood samples were drawn at the same
evaluation times and assessed for concentrations of TRP, large neutral
amino acids, kynurenine, 5-hydroxyindole acetic acid, neopterin and
biopterin. Results: During treatment with IFN-alpha, several
alterations in laboratory parameters occurred that were consistent
with an increased degradation of peripheral TRP. Psychometric ratings
revealed hardly any psychiatric changes. No consistent associations
were found between changes in the laboratory assessments determined
and the diverse psychiatric measures. Conclusion: In this study, IFN-
alpha was found to alter TRP metabolism without inducing psychiatric
side effects. Therefore, a possible relationship between TRP
metabolism and depression was not substantiated by this study.
Copyright (c) 2007 S. Karger AG, Basel.
PMID: 17873497
So? Are psoriatics just low enough in TRPytophan to be slightly
depressed?
It could explain a huge area for us.....
I'm stoked...thanks manfred for getting me to this link. <w>
And I"m not gonna get depressed because with the recent LL37 research
we're on the way to a cure....
The only LAT1 and kynurenine abstract I could find.
==============
More positive news in the Ai venue for Th1 and Th2.
http://news.biocompare.com/newsstory.asp?id=196402 ;
T Vs. B: Re-Engineered Human T Cells Effectively Target And Kill
Cancerous B Cells
9/18/2007
Source: American Association for Cancer Research
Human white blood cells, engineered to recognize other malignant
immune cells, could provide a novel therapy for patients with highly
lethal B cell cancers such as acute lymphoblastic leukemia (ALL),
according to researchers at Memorial Sloan-Kettering Cancer Center
(MSKCC). By administering repeated doses of T cells designed to
express an artificial receptor which recognizes human B cells, the
researchers were able to eradicate cancer in 44 percent of mice
bearing human ALL tumors.
Their findings, published in the September 15 issue of Clinical Cancer
Research, a journal of the American Association for Cancer Research,
show that modified T cells - the white blood cells that actively fight
infections - can be effective in fighting malignancies associated with
B cells (immune cells that create antibodies) such as chronic
lymphocytic leukaemia (CLL), ALL, non-Hodgkin's lymphoma (NHL). The
researchers have an ongoing study using these T cells in CLL, and have
recently begun the planning stages for a trial in patients with ALL.
"The immune system has evolved to police the body for infections and
diseased cells, but it has a difficult time recognizing malignant
cells since they largely appear normal to the immune system," said
lead study author, Renier J. Brentjens, M.D., Ph.D., medical
oncologist in the Leukemia Service at MSKCC. "The idea is that we can
take a patient's own T cells, re-educate them by inserting a gene into
them that will enable them to produce a receptor to recognize B cell
cancers, and then return them to the patient where they should be able
to attack and kill the tumor cells."
Because the technique uses a patient's own T cells, there is little
risk of compatibility issues or rejection, as there might be with
human stem cell transplant, Dr. Brentjens adds. Human stem cell
transplant, following radiation or chemotherapy, is currently
incorporated into the treatment of several B cell malignancies.
In order to get T cells to recognize B cells, Dr. Brentjens and his
colleagues created a gene that encodes for a cell-surface protein - an
artificial T cell receptor called a chimeric antigen receptor --
designed to specifically bind to CD19, a molecule found on the surface
of B cells and B cell cancers. Antigen receptors are what allow T
cells, in combination with other parts of the immune system, to
recognize and attack infected or malignant cells. This chimeric gene,
formed from active portions of several immune system-related genes,
creates the chimeric antigen receptor protein called 19-28z, which
does not require other co-stimulatory signals to fully activate T
cells, according to Dr. Brentjens.
Dr. Brentjens and his colleagues used an engineered retrovirus to
insert the chimeric antigen receptor gene into T cell DNA.
Retroviruses insert DNA derived from their RNA into that of a host
cell, which then uses viral vector-encoded genes to make specific
proteins. In this case, the researchers infected healthy T cells with
modified retroviruses containing the gene that codes for 19-28z. The T
cell's internal protein-making facilities then produce the chimeric
receptor as if it were one of its own natural antigen receptors.
In Clinical Cancer Research, the MSKCC researchers detail the creation
of 19-28z, their "second generation" chimeric antigen receptor, and
its effectiveness in stimulating human T cells both in culture and in
an animal model of human cancer. They also compared T cells engineered
with 19-28z to T cells engineered with a "first generation" chimeric
antigen receptor, lacking the co-stimulatory signal found in 19-28z.
Their results showed that the "second generation" 19-28z receptor was
superior to the "first generation" receptor, and that this T cell
therapy works best when administered to mice through multiple weekly
injections.
"The repeated boosts of new T cells during therapy to improve T cell
persistence enhances the efficacy of these T cells in eradicating
cancerous B cells," said Dr. Brentjens. "This concept of T cell
persistence being critical to treatment efficacy is one we are further
investigating in current and upcoming clinical trials."
The results have given the researchers further evidence that the
technique will work in humans. When transplanted back into a patient,
these engineered T cells could then attack and kill tumor cells
bearing the CD19 protein. "CD19 is not found on the surface of bone
marrow stem cells, so these modified T cells are reasonably safe since
they should not attack other blood forming cells in the bone marrow
following treatment," Dr. Brentjens said.
Based on the results of their findings, the MSKCC researchers are
currently conducting a clinical trial using this method in patients
with chemotherapy-resistant CLL. CLL is currently considered an
incurable cancer, Dr.
Brentjens said, although the disease generally progresses slowly.
------------
This DNA article looked interesting. I run in to so many good
articles.
Should I do a page? LOL
http://www.nature.com/news/2007/070917/full/070917-11.html ;
News
Published online: 21 September 2007; | doi:10.1038/news070917-11
Why a person doesn't evolve in one lifetime
The body's complicated cell-making process may help to avoid cancer.
Philip Ball
It's not easy making a human. Getting from a fertilized egg to a full-
grown adult involves a near-miracle of orchestration, with replicating
cells acquiring specialized functions in just the right places at the
right times. So you'd think that, having done the job once, our bodies
would replace cells when required by the simplest means possible.
Oddly, they don't. Our tissues don't renew themselves by mere copying,
with old skin cells dividing into new skin cells and so forth.
Instead, they keep repeating the laborious process of starting each
cell from scratch. Now scientists think they know why: it could be
nature's way of making sure that we don't evolve as we grow older1.
Evolution is usually thought of as something that happens to whole
organisms. But there's no fundamental reason why, for multicelled
organisms, it shouldn't happen within a single organism too.
In a colony of single-celled bacteria, researchers can watch evolution
in action. As the cells divide, mutants appear; and under stress,
there is a selective pressure that favours some mutants over others,
spreading advantageous genetic changes through the population.
In principle, precisely the same thing could occur throughout our
bodies. Our cells are constantly being replaced in vast numbers: the
human body typically contains about a hundred trillion cells, and many
billions are shed and replaced every day.
If this happened simply by replication of the various specialized
cells in each tissue, our tissues would evolve: mutations would arise,
and some would spread. In particular, mutant cells that don't do their
specialized job so well tend to replicate more quickly than non-
mutants, and so gain a competitive advantage, freeloading off the
others. In such a case, our wonderfully wrought bodies could grind to
a halt.
Avoiding fate
While working at the Santa Fe Institute in New Mexico, evolutionary
biologist John Pepper of the University of Arizona in Tucson and his
co-workers came up with a theory for how multicelled organisms avoid
this fate. They say it explains why the epithelial tissue cells that
line all parts of the body take such an apparently long-winded route
to replication, rather than just copying themselves in their mature
form.
To renew themselves, epithelial tissues retain a population of
undifferentiated stem cells, like the unformed cells present in
embryos, that have the ability to grow into different types of cells.
When replacements are needed, some of these stem cells divide to make
transient amplifying cells (TACs). The TACs then divide several times,
and Pepper and his co-workers think that each division produces cells
that are a little more developed into mature tissue cells.
All this costs a lot of metabolic energy, so it is not very efficient.
But, the researchers say, it means that the functions of self-
replication and proliferation are divided between separate groups of
cells. The stem cells replicate, but only a little, and so there's not
much chance for mutations to arise or for selective pressure to fix
them in place. The proliferating TACS may mutate, but they aren't
simply copying themselves, so there isn't any direct competition
between the cells to create an evolutionary pressure. As a result,
evolution can't get started.
Pepper and his colleagues have used computer modelling to show that
this proposed mechanism can suppress evolution in a long-lived,
multicelled organism.
Inside job
One case in which this scheme might not operate, they say, is in the
immune system. Here evolution is beneficial, as it introduces
adaptations that fight previously encountered invaders.
One drawback of this, however, is that it would be expected to make
the immune system more prone to cancers. And that seems to be so:
leukaemia and lymphoma are cancers associated with the immune system,
and they seem to be more common in younger people than many other
cancers, suggesting that the failure to suppress evolution allows its
problems to show up rather quickly.
Click here to access leading resaerch from Neuropsychopharmacology
The researchers think that their hypothesis could provide new insights
into cancers more generally. Whereas conventional wisdom has it that
cancer is caused by some genetic mutation that leads cells to
proliferate uncontrollably, this new picture implies that the problem
would lie with TAC mutations that interfere with differentiation - so
that a TAC cell ends up just copying itself instead of producing cells
on the next rung up on the way to mature tissue cells.
Carlo Maley, Pepper's colleague at the Wistar Institute, a biomedical
research centre in Philadelphia, Pennsylvania, says that if their
picture is right, incipient cancer formation might be detected very
early by looking for biomolecules in body fluids that signal
disruption of cell differentiation, even before there are any physical
signs of tumour growth.
((((((((((((((((((((((((((()))))))))))))))))))))))))))))
(sorry can't find the link on this one from LEF) Time to starve?
Life Extension Update Exclusive
The mitochondrial oasis
The September 21, 2007 issue of the journal Cell published a report by
scientists at Harvard, Cornell University, and the National Institutes
of Health of Health which reveals new information concerning how
calorie restriction influences longevity.
Harvard Medical School associate professor of pathology David Sinclair
and his colleagues described how the stress of calorie restriction
activates a gene known as NAMPT, which causes NAD (nicotinamide
adenine dinucleotide) to accumulate within the mitochondria of the
cell. This increases the activity of mitochondrial enzymes produced by
the genes SIRT3 and SIRT4, strengthening the mitochondria, increasing
energy output, and slowing the aging process of the cell, a process
also activated by exercise.
SIRT3 and SIRT4 are members of a class of genes known as sirtuins that
play a role in longevity. Another member of the sirtuin family, SIRT1,
was previously found to increase longevity when stimulated by
resveratrol, a compound that occurs in red grapes.
The finding further fuels the suspicion of some researchers that the
mitochondria, which are the power plants of the cells, play a vital
role in longevity. Cells can survive without other intracellular
energy sources as long as mitochondria are intact and functioning.
Commenting on his team's "mitochondrial oasis hypothesis", Dr Sinclair
explained, "Mitochondria are the guardians of cell survival. If we can
keep boosting levels of NAD in the mitochondria, which in turn
stimulates buckets more of SIRT3 and SIRT4, then for a period of time
the cell really needs nothing else."
"We're not sure yet what particular mechanism is activated by these
increased levels of NAD, and as a result SIRT3 and SIRT4," he noted,
"but we do see that normal cell-suicide programs are noticeably
attenuated. This is the first time ever that SIRT3 and SIRT4 have been
linked to cell survival."
"We've reason to believe now that these two genes may be potential
drug targets for diseases associated with aging," Dr Sinclair stated.
"Theoretically, we can envision a small molecule that can increase
levels of NAD, or SIRT3 and SIRT4 directly, in the mitochondria. Such
a molecule could be used for many age-related diseases."
Caloric restriction
Caloric restriction is the most effective and well-documented pathway
to longevity in animal studies. Both the mean and maximum life spans
of yeast, rotifers, water fleas, nematodes, fruit flies, spiders,
fish, hamsters, rats, mice, and dogs have been extended significantly
by decreasing normal caloric consumption by 30 percent to 40 percent
(Weindruch R et al 1988).
Increased life span in yeast can be induced by adding resveratrol, an
antioxidant found in red wine, to their growth medium. These results
have been replicated in both worms (Caenorhabditis elegans) and pomace
flies (Drosophila melanogaster) (Wood JG et al 2004), suggesting that
the action of resveratrol may be equivalent to that of caloric
restriction.
Recent studies at the BioMarker Pharmaceuticals laboratory have shown
that a nutrient formula from the Life Extension Foundation that
contains extracts of grape seed and skin, a whole red grape
resveratrol extract, vitamin C, and calcium (from calcium ascorbate)
can produce many of the gene expression effects found in mice on CRON.
Studies funded by the Life Extension Foundation at the Chinese Academy
of Sciences in Beijing have shown that this formula can improve the
strength and coordination of pomace flies (D melanogaster) afflicted
with a motor disorder that is similar to Parkinson's disease in
humans. This formula can protect mitochondria (the energy-generating
power plants in the cell) isolated from rat livers from damage caused
by exposure to carcinogens.
Do we really need caloric restriction or a bottle of red wine and a
whole wheat loaf under the bough?
http://www.lef.org/protocols/lifestyle_longevity/caloric_restriction_01.htm
=============================
Is this guy a flake or a prophet????
http://www.mercola.com/products/complete-probiotics
Right ideas but wrong products. The wit kit is the one you want. I
know it works....
Shall I do the CURE for everything like uwe or the above guy? LOL
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Don't eat crap...or drink bleach with a drop of vinegar?
Look at these for your considerations::
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17254747&ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Dietary omega-3 fatty acids for women.
Bourre JM.
INSERM U 705, CNRS UMR 7157, Universités Paris 7 et 5, Hôpital Fernand
Widal, 200 rue du Faubourg Saint Denis, 75745 Paris cedex 10, France.
jean-marie.bourre @fwidal.inserm.fr
This review details the specific needs of women for omega-3 fatty
acids, including alpha linoleic acid (ALA) and the very long chain
fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a
woman's adipose tissue contains a reserve of these fatty acids for the
developing fetus and the breast-fed newborn infant. This ensures the
optimal cerebral and cognitive development of the infant. The presence
of large quantities of EPA and DHA in the diet slightly lengthens
pregnancy, and improves its quality. Human milk contains both ALA and
DHA, unlike that of other mammals. Conditions such as diabetes can
alter the fatty acid profile of mother's milk, while certain diets,
like those of vegetarians, vegans, or even macrobiotic diets, can have
the same effect, if they do not include seafood. ALA, DHA and EPA, are
important for preventing ischemic cardiovascular disease in women of
all ages. Omega-3 fatty acids can help to prevent the development of
certain cancers, particularly those of the breast and colon, and
possibly of the uterus and the skin, and are likely to reduce the risk
of postpartum depression, manic-depressive psychosis, dementias
(Alzheimer's disease and others), hypertension, toxemia, diabetes and,
to a certain extend, age-related macular degeneration. Omega-3 fatty
acids could play a positive role in the prevention of menstrual
syndrome and postmenopausal hot flushes. The normal western diet
contains little ALA (less than 50% of the RDA). The only adequate
sources are rapeseed oil (canola), walnuts and so-called "omega-3"
eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA
in the diet vary greatly from person to person. The only good sources
are fish and seafood, together with "omega-3" eggs.
PMID: 17254747
And the sooner some wiz kid scientist can replace the omega-6 fat in a
pig with some cod/fish DNA and turn it in to omega-3's the better
we'll be. Otherwise the Bubba's will keep chowing down on Bar-B-Q'ed
pork ribs and die prematurely. :( <w>
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17682120&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Dietary Cod Protein Improves Insulin Sensitivity in Insulin-Resistant
Men and Women: A Randomized Controlled Trial.
Ouellet V, Marois J, Weisnagel SJ, Jacques H.
Institute of Nutraceuticals and Functional Foods, Laval University,
Quebec, Canada.
OBJECTIVE: To compare the effects of cod protein to those of other
animal proteins on insulin sensitivity in insulin-resistant human
subjects. RESEARCH DESIGN AND METHODS: Insulin sensitivity (M/I) was
assessed using a hyperinsulinemic-euglycemic clamp in 19 insulin-
resistant subjects fed a cod protein (CP) diet and a similar diet
containing lean beef, pork, veal, eggs, milk and milk products (BPVEM)
for four weeks in a crossover design study. Both diets were formulated
to differ only in protein source thus providing equivalent amounts of
dietary fibres, monounsaturated, polyunsaturated (including omega-3)
and saturated fatty acids (1.1:1.8:1.0). beta-cell function, estimated
by oral glucose tolerance test (OGTT)-derived parameters, was also
assessed. RESULTS: There was a significant improvement in insulin
sensitivity (P = 0.027) and a strong tendency for a better disposition
index (beta-cell function x M/I) (P = 0.055) in subjects consuming CP
compared with BPVEM. When taking into account median baseline M/I
(4.8x10(-3) mg.kg(-1).min(-1).pmol(-1)), an interaction on 30-min C-
peptide/30-min glucose ratio, used as an index of beta-cell function,
was observed between diet and M/I status (P = 0.022). Indeed, this
ratio strongly tended to increase in subjects with low M/I consuming
CP compared to BPVEM (P = 0.065). CONCLUSIONS: Dietary cod protein
improves insulin sensitivity in insulin-resistant individuals, and
thus could contribute to prevent type 2 diabetes by reducing the
metabolic complications related to insulin resistance.
Clinicaltrials.gov identification #NCT00400036.
PMID: 17682120
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Let's get serious now.... i'm talking Ai condition called psoriasis.
One of the Treg's we need is IL-17? Or do we have to much?
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17873879&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Lamina propria macrophages and dendritic cells differentially induce
regulatory and interleukin 17-producing T cell responses.
Denning TL, Wang YC, Patel SR, Williams IR, Pulendran B.
Vaccine Research Center and Yerkes Regional Primate Research Center,
Emory University, Atlanta, Georgia 30329, USA.
The intestinal immune system must elicit robust immunity against
harmful pathogens but must also restrain immune responses directed
against commensal microbes and dietary antigens. The mechanisms that
maintain this dichotomy are poorly understood. Here we describe a
population of CD11b(+)F4/80(+)CD11c(-) macrophages in the lamina
propria that expressed several anti-inflammatory molecules, including
interleukin 10 (IL-10), but little or no proinflammatory cytokines,
even after stimulation with Toll-like receptor ligands. These
macrophages induced, by a mechanism dependent on IL-10, retinoic acid
and exogenous transforming growth factor-beta, the differentiation of
Foxp3(+) regulatory T cells. In contrast, lamina propria CD11b(+)
dendritic cells elicited IL-17 production. This IL-17 production was
suppressed by lamina propria macrophages, indicating that a dynamic
interaction between these subsets may influence the balance between
immune activation and tolerance.
PMID: 17873879
Didn't cruiser say this area didn't hold any promise for us? I still
say we can control
Treg's from the Gi tract to cure Ai conditions.... yeah! for me.... :)
We have to stop the LPS (endogenous endotoxins) from skewing
psoriatics
toward the Th1 state.
And this area isn't all that clear, but getting clearer will happen in
the near future.
I stake my clearness on this approach.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17312112&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Invariant NKT cells amplify the innate immune response to
lipopolysaccharide.
Nagarajan NA, Kronenberg M.
Division of Developmental Immunology, La Jolla Institute for Allergy
and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
NKT cells are thought of as a bridge between innate and adaptive
immunity. In this study, we demonstrate that mouse NKT cells are
activated in response to Escherichia coli LPS, and produce IFN-gamma,
but not IL-4, although activation through their TCR typically induces
both IL-4 and IFN-gamma production. IFN-gamma production by NKT cells
is dependent on LPS-induced IL-12 and IL-18 from APC. LPS induced IFN-
gamma production by NKT cells does not require CD1d-mediated
presentation of an endogenous Ag and exposure to a combination of
IL-12 and IL-18 is sufficient to activate them. In mice that are
deficient for NKT cells, innate immune cells are activated less
efficiently in response to LPS, resulting in the reduced production of
TNF and IFN-gamma. We propose that in addition to acting as a bridge
to adaptive immunity, NKT cells act as an early amplification step in
the innate immune response and that the rapid and complete initiation
of this innate response depends on the early production of IFN-gamma
by NKT cells.
PMID: 17312112
------------------
And since GARRY found the siRNA for Ai, why can't we?
If they can use it to beat the cancer odds why can't we use it in
reverse?
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17296316&ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Silencing invariant chain of DCs enhances Th1 response using small
interfering RNA.
Ke S, Chen XH, Li H, Li JF, Gu QL, Liu BY, Zhu ZG.
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin
Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai
200025, PR China.
RNA interference (RNAi), which causes the degradation of any RNA in a
sequence specific manner, is a posttranscriptional gene silencing
mechanism. Targeting the invariant chain (Ii) in DCs has been used as
an approach to enhance antitumor immunity. It is demonstrated in this
article that transfection of H-2(K) DCs with siRNA specific for Ii
gene can significantly knock down Ii. When exposed to TNF-alpha,
immature DCs transfected with Ii siRNA can differentiate into mature
DCs without reducing viability or IL-12p70 production. Ii siRNA-
treated H-2(K) DCs exhibited an increased allostimulatory capacity in
a lymphocyte proliferation assay. Furthermore, Ii siRNA-transfected
H-2(K) DCs enhanced Th1 responses by increasing IFN-gamma and
decreasing IL-4 production, and much stronger cytotoxic activity was
observed when DCs were co-transfected with Ii siRNA and an endogenous
tumor antigen in vitro. Our findings indicate that silencing the Ii
gene in DCs with siRNA may offer a potential approach to enhancing
antitumor immunotherapy.
PMID: 17296316
==============================
http://en.wikipedia.org/wiki/Gut_flora
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99999999999999999999999999999999999999999999999999999999
88888888888888888888888888888888888888888888888888888888
77777777777777777777777777777777777777777777777777777777
666
55
4
3
2
1
Hike!
Th17 has also become my main focus for obvious reasons.
Finding the ties to the GUT seemingly
kept coming back in many articles.
http://www.signaling-gateway.org/update/updates/200708/nri2143.html
Regulatory T cells: Reciprocal regulation by retinoic acid
The vitamin A metabolite retinoic acid is a key regulator of
transforming growth factor beta (TGFbeta)-mediated differentiation of
regulatory T cells and T helper 17 (TH17) cells.
How can transforming growth factor-beta (TGFbeta) induce the
differentiation of both regulatory T cells and T helper 17 (TH17)
cells - two T-cell subsets that have opposing functions? Recent
studies have indicated that the presence of additional pro-
inflammatory cytokines, such as interleukin-6 (IL-6), is necessary for
TH17-cell differentiation. Now Mucida et al. show that the vitamin A
metabolite retinoic acid is a key regulator of TGFbeta-induced T-cell
differentiation.
The authors compared the ability of mucosal and splenic dendritic
cells (DCs) to promote the differentiation of TH17 cells and found
that, in the presence of TGFbeta and IL-6, mesenteric lymph node (MLN)
DCs were less effective than splenic DCs at inducing TH17-cell
differentiation. Because previous studies have functionally linked
retinoic acid and mucosal DCs, the authors determined whether there
was a role for retinoic acid in the reduced capacity of MLN DCs to
promote TH17-cell differentiation. The culture of T cells with MLN
DCs, TGFbeta, IL-6 and a retinoic-acid receptor (RAR) antagonist
reversed the reduced ability of MLN DCs to promote TH17-cell
differentiation, resulting in the differentiation of similar numbers
of TH17 cells as with splenic DCs. By contrast, addition of all-trans
retinoic acid to cultures with splenic DCs inhibited their induction
of TH17 cells. Retinoic acid also inhibited the expression of the TH17-
cell-associated transcription factor retinoic-acid-receptor-related
orphan receptor-gammat (RORgammat) in TH17-cell-inducing conditions.
So, retinoic acid inhibits TGFbeta- and IL-6-driven TH17-cell
differentiation. The suppressive effect of retinoic acid on TH17 cells
was also confirmed in vivo.
Next, the authors asked if MLN DCs preferentially promoted the
differentiation of TGFbeta-dependent regulatory T cells, as determined
by their expression of forkhead box P3 (FOXP3). MLN DCs induced more
FOXP3+ T cells in the presence of TGFbeta compared with splenic DCs.
The addition of a RAR antagonist reduced this TGFbeta-dependent FOXP3
induction, whereas addition of retinoic acid enhanced it. Regulatory T
cells generated in the presence of both TGFbeta and retinoic acid were
functional in vivo and protected mice from colitis, whereas TGFbeta-
induced regulatory T cells were only partially protective.
Under conditions that promote TH17-cell differentiation (TGFbeta and
IL-6), retinoic acid induced the differentiation of regulatory T
cells, indicating that retinoic acid might override the promotion of
TGFbeta-induced TH17-cell differentiation by IL-6.
So, the data show that retinoic acid regulates the reciprocal
differentiation of TGFbeta-induced regulatory T cells and TH17 cells.
This study has important implications for the understanding of vitamin
A deficiency and highlights the therapeutic potential of retinoic acid
in diseases in which there is an imbalance in the numbers of TGFbeta-
dependent TH17 cells and regulatory T cells.
More recently, three papers published in The Journal of Experimental
Medicine (see Further Reading) show that the induction of regulatory T
cells by DCs in the gut depends on TGFbeta and retinoic acid,
highlighting a specific role for retinoic acid in the mucosal immune
system.
+++++++++++++++++++++++++++++++++++++++++++++++++++
Something NEW in the IMMUNE neighborhood. A fix will have to
include a genetic fix for psoriasis or so some assume.
http://news.biocompare.com/newsstory.asp?id=193092
New DNA-Stitching Mechanism Important In Immune System
Source: Howard Hughes Medical Institute
The immune system has a collection of strategies to help it fend off
invaders - and researchers have just uncovered a new one. Scientists
have long known that to generate the assortment of antibodies needed
to recognize a diverse array of potential foes, immune cells shuffle
segments of their genes into different combinations. Researchers have
now found that in mending the DNA broken during this process, cells
can employ a type of DNA repair that is fundamentally different than
the classical method.
Howard Hughes Medical Institute investigator Frederick Alt and his
colleagues published their discovery in the August 22, 2007, advance
online publication of the journal Nature. First author was Catherine
Yan in the Alt laboratory at The Children's Hospital and Harvard
Medical School. The finding highlights the surprising importance of
the alternate DNA repair mechanism in one of the most fundamental
processes in the immune system, said the researchers. Also, they said,
there are hints that the repair mechanism might play a role in the
abnormal chromosomal rearrangements that underlie lymphomas.
The researchers explored how broken DNA is repaired in B cells, which
are specialized immune cells that produce antibodies. Antibodies are
proteins that recognize and attach to telltale components, called
antigens, of foreign invaders such as viruses and bacteria, in order
to destroy them. To generate specialized antibodies that can transport
their antigen cargoes to specific destinations, B cells use a process
called class switch recombination (CSR), in which genes for the
antibodies are snipped and rearranged to produce different antibody
types. The snipped-apart DNA must then be rejoined. Researchers have
believed that B cells use a process called classical non-homologous
end-joining for such repair.
To test whether this classical process is, indeed, involved in CSR,
the researchers genetically knocked out two critical components of the
end-joining machinery, proteins known as XRCC4 and Ligase 4.
Eliminating these proteins reduced the B cells' ability to rejoin DNA
broken in CSR, suggesting that classical end-joining was important.
But lots of class switching still occurred, and the researchers
speculated that an alternate method of rejoining DNA ends must exist.
When they analyzed what kind of DNA breaks were repaired in the
absence of CSR, they found that the alternate end-joining mechanism
appeared to work only on pairs of broken DNA ends that had
microhomologies. Microhomologies are short regions of overhanging
single-stranded DNA that give the two broken DNA segments a
complementarity-like two pieces of a puzzle fitting together.
"This finding tells us that something different is going on with this
pathway that makes it strongly prefer microhomologies," said Alt. The
next step, he said, is to explore exactly what characteristics of a
DNA break trigger the cell to use the classical or alternate end-
joining process. For example, he said, other researchers had found
evidence that CSR tends to produce breaks with particularly long
microhomologies, which might be preferentially repaired by the
alternate process. "It may be that the two pathways are working in
competition, and that the nature of the DNA substrates governs which
one wins in each case," said Alt.
The researchers also plan studies to identify the components of the
alternate end-joining machinery, said Alt. "While there could be some
novel components, we think this pathway probably uses a subset of
factors that are used for other DNA repair pathways," he said. "Once
we have identified those components, we can dissect in normal cells
what specialized role this repair pathway plays," he said.
Importantly, the Alt lab has generated evidence that the alternate
pathway might have detrimental effects-catalyzing aberrant chromosomal
rearrangements, or translocations, that underlie lymphomas that arise
in mice lacking components of the classical pathway and the p53
checkpoint protein.
"We don't really know if this is a `bad' pathway," said Alt. "However,
our studies indicate that in the absence of the classical joining
process, up to twenty percent of the breaks in CSR that do not get
repaired get joined to other chromosomes as translocations," said Alt.
"So, for some reason the alternate pathway very effectively catalyzes
translocations." He also noted that studies done by others have
indicated that the translocations that underlie many B cell lymphomas
show microhomologies, which implies that they are being produced by
the alternate pathway.
The alternative pathway had already been implicated from other studies
but was not thought to function on chromosomal DNA. "Based on our
current findings, this pathway will clearly be given more serious
consideration, both for its ability to repair normal chromosomal DNA
damage and for its ability to catalyze unwanted end-joins such as
translocations,' said Alt
-----------
Hey! How many times have I groaned on with th1 and th2 teeter totter
of immunity?
That would be 181 times now. 182 If you consider this post.
http://groups.google.com/groups/search?qt_s=1&q=th1+th2+randall
If you've been reading my posts You know.
You may think (or hypothezise) that i'm on the wrong track. And I was
till they found this IL-17 (Th-17) linkages.
Let's look at a current abstract this WEEK for psoriasis found on
pubmed.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17715172&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Cytokines in arthritis the 'big numbers' move centre stage.
Gaston JS.
Division of Rheumatology, Department of Medicine, University of
Cambridge.
More than 20 yrs ago, T-helper lymphocytes were divided into Th1 and
Th2 subsets on the basis of their cytokine production. The pro-
inflammatory Th1 subset was considered predominant in inflammatory
arthritis, but evidence for this notion was incomplete, and some
called into question the role of helper T cells. The identification of
a novel T cell subset, Th17 cells, which appears to be critical for
several forms of autoimmune inflammation, including arthritis,
requires a reconsideration of arthritis pathogenesis and the role of T
cells. This review deals with several of the newly described ('big
number') cytokines which are involved in the differentiation and
action of Th17 cells, and pays particular attention to the
pathogenesis of spondyloarthritis because of the implication of the
same cytokine networks in psoriasis and inflammatory bowel disease.
The role of dendritic cells as coordinators of T cell differentiation
in response to pathogen-derived signals in also emphasized.
PMID: 17715172
Scientific research has taken this tack, a Th1 versus a Th2 skew and
now they've filled in the blanks with Th17.
----------
So what is this all about? How does LPS figure in to the P curve? LPS
keeps the teeter totter stuck on Th1.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17716858&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Sympathetic nervous modulation of the skin innate and adaptive immune
response to peptidoglycan but not lipopolysaccharide: Involvement of
beta-adrenoceptors and relevance in inflammatory diseases.
Manni M, Maestroni GJ.
Istituto Cantonale di Patologia, Center for Experimental Pathology,
Via in Selva 24, P.O. Box, 6601 Locarno, Switzerland.
Disorders of the skin immune activity are implicated in the
pathogenesis of acquired inflammatory skin disorders. Inflammatory
diseases including psoriasis, atopic dermatitis, lichen planus and
vitiligo have also been associated with local alterations of
adrenergic mechanisms and emotional stress. Here we show that the beta-
adrenergic receptors antagonist propranolol along with peptidoglycan,
but not LPS, combined with intradermal injection of a soluble protein,
shifted the recall memory response to the Th1 type. The specific beta2-
AR antagonist ICI 118,551 did not reproduce this effect suggesting
that inhibition of both beta1- and beta2-AR caused the Th1
polarization. The underlying mechanism included enhanced local
expression of IFN-gamma, IL-12 and IL-23 as well as of IFN-beta and
CXCR3 ligands during the innate phase of the response which resulted
in an increase of antigen-positive plasmacytoid dendritic cells (pDCs)
in the draining lymph node. In particular, modulation of inflammatory
cytokines, and IFN-beta inducible genes expression appeared to involve
also the beta1-AR. Plasmacytoid dendritic cells and IL-23 were
recently reported to play a central role in the pathogenesis of Th1-
sustained inflammatory skin diseases such as psoriasis. Thus, primary
beta-adrenoceptors signaling defects or altered sympathetic nervous
activity together with selected pattern recognition receptors
activation might serve as initiation and/or persistence factors for
numerous Th1-sustained inflammatory skin diseases.
PMID: 17716858
------------
http://en.wikipedia.org/wiki/Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars
and amino acids that forms a mesh-like layer outside the plasma
membrane of eubacteria. The sugar component consists of alternating
residues of -(1,4) linked N-acetylglucosamine and N-acetylmuramic
acid residues. Attached to the N-acetylmuramic acid is a peptide chain
of three to five amino acids. The peptide chain can be cross-linked to
the peptide chain of another strand forming the 3D mesh-like layer.
Some Archaea have a similar layer of pseudopeptidoglycan.
Peptidoglycan serves a structural role in the bacterial cell wall,
giving the wall shape and structural strength, as well as
counteracting the osmotic pressure of the cytoplasm. Peptidoglycan is
also involved in binary fission during bacterial cell reproduction.[1]
The peptidoglycan layer is substantially thicker in Gram-positive
bacteria (20 to 80 nm) than in Gram-negative bacteria (7 to 8 nm),
with the attachment of the S-layer. Peptidoglycan forms around 90% of
the dry weight of Gram-positive bacteria but only 10% of Gram-negative
strains. In Gram-positive strains, it is important in attachment roles
and serotyping purposes.[2]
--------------
Let's see if the RANDALL has actually brought up peptidoglcan once or
twice....
Someone who said my thoughts are related to my a$$$hole, seems to
think i'm on the wrong track. Right?
Am I? LOL :-)
Oh look! A bunch of randall hits for peptidoglycan,
http://groups.google.com/groups/search?qt_s=1&q=peptidoglycan+randall
Will the P cure sPring from the dePths of the Gi tract? LOL
Or all the mechanics needed found in the skin.... the skinny will be
known? lol
------------
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17717033&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
IgG, IgA, IgM antibodies to a viral citrullinated peptide in patients
affected by rheumatoid arthritis, chronic arthritides and connective
tissue disorders.
Anzilotti C, Riente L, Pratesi F, Chimenti D, Sedie AD, Bombardieri S,
Migliorini P.
Clinical Immunology Unit and Clinical Rheumatology Unit, Department of
Internal Medicine, University of Pisa, Pisa, Italy.
Objectives. Anti-citrullinated protein/peptide antibodies (ACPA), a
family of antibodies with overlapping specificities, represent a
specific marker of rheumatoid arthritis (RA). The aim of the present
study is to investigate the prevalence and clinical significance of
IgG, IgA and IgM ACPA by a newly described assay employing a viral
citrullinated peptide (VCP). Methods. IgG, IgA and IgM anti-VCP
antibodies have been measured in sera from 146 patients affected by RA
and 404 controls, including 204 chronic arthritides, 111 connective
tissue disorders and 89 healthy subjects. The affinity of the
different isotypes for VCP was analysed by liquid phase inhibition
assays. Results. Among RA patients, 40 were single positive for IgG
anti-VCP, five for IgA and 11 for IgM. Ten patients were double
positive for IgG and IgA, four for IgG and IgM, six for IgA and IgM.
In 15 RA patients IgG, IgA and IgM anti-VCP antibodies were detected.
No correlation could be found between the isotype and the clinical
manifestations or duration of the disease. IgA anti-VCP were strongly
associated with RA, whereas IgM anti-VCP were detected also in a low
percentage of systemic lupus erythematosus, ____psoriatic
arthritis____ and mixed cryoglobulinaemia (MC) patients. IgG anti-VCP
displayed a higher affinity for the antigen than IgA or IgM.
Conclusions. These data show that anti-VCP of IgG and IgA isotype
discriminate RA from other chronic arthritides and disease controls
and suggest an independent production of each isotype.
PMID: 17717033
IGM we're talking now? But for PsA and not psoriasis.
So, it would be a gene for those with p and psa?
That sounds like a lead to me?
------------
Here's a big study and important for the immune equations.
http://news.biocompare.com/newsstory.asp?id=192875 ; ;
Scientists Find Clue To Mechanisms Of Gene Signaling And Regulation
Source: Emory University
Scientists have discovered a pattern in the DNA sequence of the mouse
genome that may play a fundamental part in the way DNA molecules
regulate gene expression. The research, led by Emory University
scientists along with colleagues at Jacobs University, Bremen,
Germany, will be published in the Aug. 22 Advance Online publication
of the journal Nature.
Ever since scientists cracked the basic code of chemical bases that
comprise the genome of humans and animals, scientists have been
uncovering layers of other chemical modifications of gene functioning
that can be inherited along with the DNA sequence. This field of
discovery, called epigenetics, turns out to be just as important as
the genetic sequence itself in controlling whether genes are turned on
or off, which determines whether or not they manufacture proteins.
For the past several decades, scientists have known that DNA
methylation, a biochemical reaction that adds a methyl group to DNA,
is one of these epigenetic processes that marks genes for silencing,
which means they do not manufacture proteins. Another kind of
modification, called histone methylation, also marks histone proteins
that are part of the complex packaging of DNA within the nucleus of
cells.
How and where this critical selection process is accomplished--for
either silencing or expression-- has been a mystery, however. DNA
methylation occurs across the animal genomes, almost always at the C
base position of a CG dinucleotide (sequence of two base pairs) in the
genetic sequence.
Most expressed genes are based on the simultaneous expression of two
copies of a geneÑone from the mother and one from the father. A small
subset of genes, however, are allele-expression specific, meaning only
one copy of the gene is expressed, from either the mother or the
father, with the gene from the other parent being methylated, or
silenced. This kind of differential gene expression is called
"imprinting." In the mouse genome, about 80 genes are imprinted.
The Emory and Bremen researchers discovered a biochemical pattern they
believe may be a signal to the epigenetic machinery that a particular
gene should be imprinted. In the regions of the genome where genes are
imprinted, called differentially methylated regions, they found a
repeat pattern (periodicity) of 8 to 10 base pairs between two CG
dinucleotides. The periodicity is consistent with the structural
information from the enzyme responsible for the methylation. The
enzyme structure was solved by use of X-ray crystallography at the
Advanced Photon Source of Argonne National Laboratory.
"We believe that this repeating pattern of 8 to 10 base pairs between
CGs provides a signal for where the differential methylation should
take place," says senior author Xiaodong Cheng, PhD, Emory professor
of biochemistry and a Georgia Research Alliance eminent scholar. "So
far only about 20 regions of differential methylation have been
identified in the mouse genome, and we wanted to find out how those
regions compared to the rest of the genome."
"Now we can use this new information to find out if any other areas
with such 8 to 10 base pair repeats are also differentially
methylated. We want to discover how many regions of differential
methylation exist and whether or not this imprinting has any impact on
disease development."
Scientists already have learned that cancer genes contain "islands" of
CG concentrations that are abnormally methylated. Dr. Cheng and his
colleagues will focus on these CG islands, trying to discover whether
they contain the same repeating pattern as the differentially
methylated regions.
-----------------
http://www.medicalnewstoday.com/articles/80451.php
How Bacteria Make The B Vitamin Folate
Some biochemical processes, especially those in bacteria, have been so
well studied it's assumed that no discoveries are left to be made. Not
so, it turns out, for Johns Hopkins researchers who have stumbled on
the identity of an enzyme that had been a mystery for more than 30
years. The report appears in Structure.
"It was really quite a surprise when we realized we had discovered the
unknown player in how bacteria make the B vitamin folate, a player
that we've known of since 1974," says study author L. Mario Amzel,
Ph.D., professor and director of biophysics and biophysical chemistry
at Hopkins. "Basic research can be so serendipitous at times."
Amzel and colleague Maurice Bessman and their labs were in the middle
of systematically characterizing how members of a family of related
enzymes in bacteria can recognize specific molecules. With each family
member, they isolated purified enzyme, grew crystals of pure enzyme,
and figured out the enzyme's 3-D structure by using techniques that
use X-rays.
Armed with the 3-D structure, they then used computer modeling to
analyze how the enzyme binds to and acts on another molecule, its
substrate.
"We still didn't know that it was anything special until Maurice
started searching old publications," says study author Sandra Gabelli,
Ph.D. "As it turns out, Suzuki and coworkers in 1974 had published
evidence of an enzyme in the bacteria E. coli with similar
characteristics to ours that could initiate folate biosynthesis."
"So we had to ask, Can the bacteria make folate if we remove the orf17
gene"" says Amzel. Bessman and colleagues then "knocked-out" the gene
and, predictably, the bacteria made 10 times less folate than usual.
"It was such a sweet discovery," says Gabelli. "It's scientific
discovery the old-fashioned way, finding something we weren't looking
for."
The mechanics behind how bacteria make folate are of particular
interest to scientists who want to design more powerful antibacterial
drugs. Humans cannot make folate because they do not have any of the
same molecular machinery. Therefore, it's possible to design drugs
that target the bacterial folate machinery that would not lead to side
effects in humans.
Their discovery, says Amzel, identifies yet another potential
antibacterial target. "We are not in that business of drug design --
we're focused on the basics, figuring out how things work," he says.
"We do hope that others can use what we find to make new drugs."
=======================
Broccoli Compound Could Boost Immune System, Fight Cancer
http://www.medicalnewstoday.com/articles/80274.php
--------------
Whoops... this is getting long. i"ll keep the info i've got for the
next post.
randall... going immunologically wacky once again.
manfred
> Nonsense. Drinking bleach with vinegar or drinking hydrogen peroxide
> are all quackery. Using it topically may help for NON autoimmune
> conditions.
>
Chlorine dioxide is NOT ordinary household bleach! DO NOT try
drinking bleach!!
randall
OK...
What I reacted to was this:::
> MMS is a stabilized oxygen formulation that is a 28% solution of
> Sodium Chlorite in distilled water. When ordinary white vinegar is
> added to a few drops of MMS, Chlorine Dioxide is created and when
> ingested, it kills virtually every known pathogen, including bacteria,
> viruses, fungi, molds, and yeasts.
--------------
Since I haven't the faintest idea what MMS is, the next term, sodium
chlorite
provided my basis for the comments.
And it looks like I made a mistake.
http://en.wikipedia.org/wiki/Sodium_chlorite
sodium hyPochlorite is the bleach,
http://en.wikipedia.org/wiki/Sodium_hypochlorite
------------
All those pretty pictures and the broken link to their website most
likely
influenced my thinking. lol
sorry
Should I go back and listen or stay rather closed minded?
Let me think....
Ok, i've poured some bleach down the well a few times....
Think i'll find something more topical...MKP5....
randall
manfred
> On Sep 28, 3:30 pm, manfred <manfre...@lycos.com> wrote:
>
> > > Nonsense. Drinking bleach with vinegar or drinking hydrogen peroxide
> > > are all quackery. Using it topically may help for NON autoimmune
> > > conditions.
>
> > Chlorine dioxide is NOT ordinary household bleach! DO NOT try
> > drinking bleach!!
>
> OK...
>
> What I reacted to was this:::
>
> > MMS is a stabilized oxygen formulation that is a 28% solution of
> > Sodium Chlorite in distilled water. When ordinary white vinegar is
> > added to a few drops of MMS, Chlorine Dioxide is created and when
> > ingested, it kills virtually every known pathogen, including bacteria,
> > viruses, fungi, molds, and yeasts.
>
> --------------
>
> Since I haven't the faintest idea what MMS is, the next term, sodium
> chlorite
> provided my basis for the comments.
>
>
> sodium hyPochlorite is the bleach,http://en.wikipedia.org/wiki/Sodium_hypochlorite
>
> ------------
>
> All those pretty pictures and the broken link to their website most
> likely
> influenced my thinking. lol
>
> sorry
>
> Should I go back and listen or stay rather closed minded?
>
> Let me think....
>
> Ok, i've poured some bleach down the well a few times....
>
> Think i'll find something more topical...MKP5....
>
> randall
The intent of my post was to point out that there is a theory that
infections often not only trigger P but could possibly be lingering in
our bodies and that getting rid of the infection may get rid of the
P. I don't dispute that it is in the genes but there is something
that pulls the trigger.
If you look at these two links you would have found out what MMS is
(Miracle Mineral Supplement: the name reeks of hocus-pocus, I know).
Easily understood info at:
http://www.webtalkradio.net/content/view/32/33/
Part 1 of his book is at
http://www.miraclemineral.org/part1.php
However, if it cleans up Malaria, etc, maybe it could clean up colds,
oral herpes, and the dreaded strep which all make my skin go
ballistic. That alone would be a great benefit to many.
I should have taken the time to explain where I was going with the
infection-MMS thing but sometimes I don't have the time to be chatty
and just give the basics thinking you will investigate.
>From http://www.bioredox.mysite.com/CLOXhtml/CLOXilus.htm
Sodium chlorite (NaClO2) can be acidified as a convenient method to
produce chlorine dioxide (ClO2) which is a strong oxidant and a potent
disinfectant.
A protocol has been developed whereby a solution of these compounds
can be taken orally. This procedure rapidly eliminates malaria and
other infectious agents in only one dose. Chlorine dioxide (ClO2) is
highly reactive with thiols (RSH), certain amino acids and iron, all
of which are necessary for the growth and survival of pathogenic
microbes. Properly dosed this new treatment is tolerable orally with
only transient side effects. More research to better document efficacy
in malaria and in other infections is urgently called for.
DISCOVERY
Jim Humble, a modern gold prospecting geologist, needed to travel to
malaria infested areas numerous times. He or his coworkers would on
occassion contract malaria. At times access to modern medical
treatment was absolutely unavailable. Under such dire circumstances it
was found that a solution useful to sanitize drinking water was also
effective to treat malaria if diluted and taken orally. Despite no
formal medical training Mr. Humble had the innate wisdom to experiment
with various dosage and administration techniques. Out of such
necessity was invented an easy to use treatment for malaria which was
found rapidly effective in almost all cases....
[I'm not going to post all of this here but this is what is covered]
MATERIALS AND METHODS....
EXPLORING BENEFITS......
OXIDANTS AS PHYSIOLOGIC AGENTS.....
(Includes How Oxidants Stimulate Immunity, including the OONO cycle)
OXIDES OF CHLORINE AS DISINFECTANTS
MALARIA IS OXIDANT SENSITIVE
TARGETING THIOLS
HEME IS AN OXIDANT SENSITIZER
OVERCOMING ANTIBIOTIC RESISTANCE WITH OXIDATION
SOME INCOMPATIBILITIES
REDUCTANT RECOVERY SYSTEMS
TARGETING POLYAMINES
TARGETING PURINES
TARGETING PROTEINS
SAFETY ISSUES
MORE RESEARCH
....Chlorine dioxide (ClO2) has been proven to be cidal to almost all
known infectious agents in vitro using remarkably low concentrations.
This includes parasites, fungi, bacteria and viruses. The experiences
noted above imply that this compound is tolerable orally at effective
concentrations. Therefore extensive research is warranted to determine
if acidified sodium chlorite is effective in treating other
infections. We may be on the verge of discovering the most potent and
broad spectrum antibiotic yet known. Special thanks go to Jim Humble
for his willingness to share his discovery with the world.
by Thomas Lee Hesselink, MD
______________________________________________________________________
Cruiser,
I like your folic acid theory. What else with it? Vitamin C? NAC? I
have been reading some stuff about high dose folic acid. Are you
trying it? I would like it even more if I saw you getting good
results!
randall
I thought my LL-37 post implicated DNA once and for all?
>
> If you look at these two links you would have found out what MMS is
> (Miracle Mineral Supplement: the name reeks of hocus-pocus, I know).
>
> Easily understood info at:http://www.webtalkradio.net/content/view/32/33/
The link doesn't work very well. I did try to listen.
>
> Part 1 of his book is athttp://www.miraclemineral.org/part1.php
If you spend the ten bucks let me know. LOL
>
> However, if it cleans up Malaria, etc, maybe it could clean up colds,
> oral herpes, and the dreaded strep which all make my skin go
> ballistic. That alone would be a great benefit to many.
Look. Bill and Melinda GAtes are working on this problem.
http://www.msnbc.msn.com/id/20920343/site/newsweek/
And their doing cheapO meds for poor folks. So, why don't
you tip them off to this stuff.
It could be a bigger break through then uwe's cure all..
Someone could get a noble peace prize out of this. <w>
Or at least a humanitarian award of some sort.
Here sign up for their group and submit the mms for malaria.
http://groups.google.com/group/global-health-delivery/topics?start=
>
> I should have taken the time to explain where I was going with the
> infection-MMS thing but sometimes I don't have the time to be chatty
> and just give the basics thinking you will investigate.
Yes, but that link above if it worked better would have really helped
out.
>
> >Fromhttp://www.bioredox.mysite.com/CLOXhtml/CLOXilus.htm
Hey! I doubled my dosage of folic acid.... I went from one or two
400 mcg's to up to four a day. Let's see. That would be 1.6 mg's.
Now when I take it out of the mix we shall see what it does or did.
LOL
I have a funny feeling though, that my current clearings are mostly
due to NAG.... and a few of the herbals i'm on.
randall...
randall
I've got an idea.
Just as I tested shegoi
http://www.reallywell.com/larrea.htm
to lower possible viral culprits in psoriasis pathogenesis,
http://groups.google.com/groups/search?qt_s=1&q=shegoi+herpes+psoriasis
you could use this next one. It seemingly is much more efficacious
then MMS.
http://www.vrp.com/ProductPage.aspx?ProdID=1475
Fucoidan is an important addition to the body's virus-combating
arsenal. It is produced from Fucus versiculosus <sniP>
(no joke intended JX... & by the _beaver_, i meant Jerry Mathers the
prior NPF spokesperson <w>)
What is Fucus vesiculosus? (no R in the sPelling?)
http://www.fugleognatur.dk/gallery_showlarge.asp?ID=14898
&
Bladderwrack (Fucus vesiculosus)
http://www.theseashore.org.uk/theseashore/SpeciesPages/Bladderwrack%20French.jpg.html
------------
http://en.wikipedia.org/wiki/Fucoidan
After reading this i want to eat a seaweed salad. :)
http://luvsushi.com/kotobuki/Kotobuki%20Wakame%20Salad.JPG
I don't know about Fucoidan as a salad. I should google that later. :)
Fucoidan has extensive scientific review: (704 hits)
http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed&cmd=Search&Term=fucoidan%20&itool=QuerySuggestion
Sounds even better then MMS. I would love to see a page made for
it with rainbows like the mms page... offering a miracle cure for ALL
aliments/diseases
including psoriasis. LOL
But to folks with STD's it is a miracle drug. LOL
But, lets face it, after the last fifty years I've seen to many
miracle supplements/drugs that
failed to deliver for psoriasis. Could genetic diversity be behind it?
LOL
Why would a person whose _genetically_ skewed to the Th1 side, need
anything of this
nature? Most psoriatics don't get as many aliments as the population
at
large as a result of the Th1 skew, provided their lifestyle is fairly
healthy. Like
JX's for example. Or mine...
Wouldn't seaweed (fucoidan) have all the minerals including chlorine,
(it does grow in salt water)
needed to do what MMS does?
Look at how healthy the traditional diet in Japan is..... all the
seaweed and sushi/shashimi...
OH and,
You'll need to find my posts, after my usage of shegoi
(aka-- Larrea tridentata, Chaparral, creosote bush)
to get my impressions. Iirc, they were somewhat positive but once
again,
not the P savior. Why spend the bucks when further dietary prophylaxis
is whats
called for?
http://en.wikipedia.org/wiki/Prophylaxis
And since your on P meds now, what happens to all the Th1 cells that
are blocked?
The ones that keep us from getting sicker or sick in the first place?
http://en.wikipedia.org/wiki/T_helper_cell
Isn't this the basis for iatrogenesis? Psoriatics get vainly lured in
to the sun
and then, while on many p meds get burnt to a crisP? Makes me wonder
where the sunshine overdose and drug article abstracts are? Couldn't
this syndrome of drugs and ill dietary prophylaxis, lead to skin
melanoma's? For all we know. I suspect it does. Sunshine (vitamin D)
trumps
some of the P pathways and if you may continue eating foods high in
omega-6's, it's
my distinct impression this is causing carcinogenesis. It's rampant
now.
http://en.wikipedia.org/wiki/Iatrogenesis
&
http://en.wikipedia.org/wiki/Carcinogenesis
Since no one can find the elusive antigen or suPerantigen for
psoriasis,
there must not be one. Right?
http://en.wikipedia.org/wiki/Superantigen
http://en.wikipedia.org/wiki/Antigen
http://groups.google.com/groups/search?qt_s=1&q=superantigens+randall+psoriasis
What keeps the psoriatic Th1 skewed in the first place is LPS
(endogenous endotoxins).
http://groups.google.com/groups/search?q=lps+randall+psoriasis&qt_s=Search
How LPS works is via permeability in the Gi tract. We've been over
this a zillion times now.
http://groups.google.com/groups/search?q=lps+randall+psoriasis+permeability&qt_s=Search
OTOH we can look at severe alcoholics and not see any psoriasis/
psoriatics. And we
know that alcohol increases PASi severity. So? It has to be a gene.
And since LL-37 is making this p puzzle work. We look at it further as
that is
what makes sense....
Back to alcohol and the NPF.
http://www.psoriasis.org/publications/advance/200501_alcohol.php
[...]
Alcohol appears to affect psoriasis in men more strongly than in
women. One study found that heavy drinking actually lowered treatment
response in men. Other studies have shown that men with psoriasis
drink more than men without, that there is a significantly higher
incidence of psoriasis in alcoholics, and that abstinence can improve
the severity of the disease.
Dr. Naldi confirms that "data concerning alcohol consumption are less
clear-cut. It seems that only young men who are heavy drinkers are at
a higher risk for psoriasis, but other studies have shown that
drinking alcohol has a negative effect on clinical response to
treatment and on the likelihood of remission."
In addition, it should be noted that alcohol can have dangerous side
effects when combined with certain psoriasis medications, such as
methotrexate or acitretin (brand name Soriatane) in women of child-
bearing potential. <sniP>
--------------
But note the iatrogenesis with drugs and alcohol, manfred, further
complicating this condition.
More psoriatics are prone to drink and it increases psoriasis. Why? I
know
i've posted many times my suppositions and theories all supported by
ample abstracts.
(437 hits on pubmed for keywords: alcohol psoriasis )
------
The one alcholic product that seems to Help psoriasis, used in
moderation is red wine-
high in resveratrol, i've found. And that takes us back to P53 genes.
P53 and P, (71 hits)
http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed&cmd=Search&Term=p53%20psoriasis&itool=QuerySuggestion
Resveratrol and p53-- (82 hits on pubmed)
REsveratrol increases/activates SirT1....
keywords:: resveratrol sirT1 and p53 ( seven hits on pubmed)
Lets look at some sirtuin 1 hits that are current.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17804521&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The Effect of Resveratrol on a Cell Model of Human Aging.
Stefani M, Markus MA, Lin RC, Pinese M, Dawes IA, Morris BJ.
School of Medical Sciences, University of Sydney, Sydney, New South
Wales, Australia.
The natural polyphenol resveratrol stimulates sirtuins and extends
lifespan. Here resveratrol inhibited expression of replicative
senescence marker INK4a in human dermal fibroblasts and 47 out of
19,000 genes from microarray experiments were differentially
expressed. These included genes for growth, cell division, cell
signaling, apoptosis and transcription. Genes involved in Ras and
ubiquitin pathways, Ras-GRF1, RAC3 and UBE2D3, were downregulated. The
changes suggest resveratrol might alter sirtuin-regulated downstream
pathways, rather than sirtuin activity. Serum deprivation and high
confluency caused nuclear translocation of the SIRT1-regulated
transcription factor FOXO3a. Our data indicate resveratrol's actions
might cause FOXO recruitment to the nucleus.
PMID: 17804521
==========================
OK? Now lets look at foxo3a & foxp3 and other forkHEADs. lol
http://en.wikipedia.org/wiki/Foxp3
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15719167&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Forkhead transcription factors in immunology.
Jonsson H, Peng SL.
Division of Rheumatology, Department of Internal Medicine, Washington
University School of Medicine, 660 S. Euclid Ave., St. Louis, MO
63110, USA.
The forkhead (Fox) gene family comprises a diverse group of "winged-
helix" transcription factors that play important roles in development,
metabolism, cancer and aging. Recently, several forkhead genes have
been demonstrated to play critical roles in lymphocyte development and
effector function, including Foxp3 in the development of regulatory T
cells, Foxj1 and Foxo3a in the regulation of CD4+ T cell tolerance,
and Foxn1 in thymic development. Roles for other forkhead genes have
also been proposed, including Foxp1 in macrophage differentiation,
Foxq1 in natural killer cell effector function and Foxd2 in T cell
activation. Thus, forkhead genes promise insight into the mechanisms
of immunoregulation in several immune cell lineages, and their
dysregulation likely contributes to the pathogenesis of several
immunological disorders, suggesting that their study will lead to the
development of novel therapeutic agents.
PMID: 15719167
------------------------------
Now look at foxP3 and psoriasis.
[...]
BACKGROUND: Depletion of CD4+ CD25+ Foxp3+ naturally occurring
regulatory T cells (T(reg)) induces autoimmune phenomena.
[...]
PMID: 16902287
------------------
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16902287&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Immunohistochemical analysis of regulatory T cell markers FOXP3 and
GITR on CD4+CD25+ T cells in normal skin and inflammatory dermatoses.
de Boer OJ, van der Loos CM, Teeling P, van der Wal AC, Teunissen MB.
Department of Pathology, Academic Medical Center, University of
Amsterdam, Amsterdam, The Netherlands. o.j.d...@amc.uva.nl
Regulatory T cells (Treg) are a subset of T lymphocytes that play a
central role in immunologic tolerance and in the termination of immune
responses. The identification of these cells in normal and
inflammatory conditions may contribute to a better understanding of
underlying pathology. We investigated the expression of FOXP3 and GITR
in normal skin and in a panel of different inflammatory dermatoses.
Immunohistochemical double stainings in skin tissue sections revealed
that FOXP3 and GITR were almost exclusively present on T cells that
express both CD4 and CD25. Further, immunohistochemical double
staining, as well as fluorescence-activated cell sorter analysis, on
peripheral blood T cells showed that most FOXP3(+) cells expressed
GITR and vice versa, whereas a minority were single-positive for these
markers. The mean frequency of FOXP3(+) T cells in spongiotic
dermatitis, psoriasis, and lichen planus was in the same range
(25-29%), but the frequency of these cells in leishmaniasis appeared
to be lower (approximately 15%), although this was not statistically
significant. The mean frequency of GITR(+) T cells was fairly similar
in all conditions studied (14-20%). Normal human skin also contained
FOXP3(+) and GITR(+) cells in the same frequency range as in diseased
skin, but the absolute numbers were, of course, much lower. In
conclusion, frequencies of FOXP3(+) and GITR(+) T cells were similar
in all inflammatory skin diseases studied and normal skin, despite the
well-known differences among the inflammatory conditions under
investigation.
PMID: 17478450
==================
Yesterday I mentioned I was going to expand my resveratrol trials. <g>
I even posted from Omar Khayyám's rubaiyaas regarding wine.
(Rubaiyat).
http://en.wikipedia.org/wiki/Omar_Khayy%C3%A1m
While on poetry, i wouldn't miss the prophet by Khalil Gibran,
http://en.wikipedia.org/wiki/The_Prophet_%28book%29
http://en.wikipedia.org/wiki/Khalil_Gibran
----------------
Sorry for the segue....But what's better then a beautiful poem?
CLEAR SKIN> lol
Let's get down to BRASS tacks....
Take a deeP breath and get that nitric oxide going, that cruiser is so
keen on now.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17875988&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Nitric oxide induces CD4+CD25+ Foxp3 regulatory T cells from CD4+CD25
T cells via p53, IL-2, and OX40.
Niedbala W, Cai B, Liu H, Pitman N, Chang L, Liew FY.
*Division of Immunology, Infection, and Inflammation, Glasgow
Biomedical Research Centre, 120 University Place, University of
Glasgow, Glasgow G12 8TA, United Kingdom.
The principal aim of the immune system is to establish a balance
between defense against pathogens and avoidance of autoimmune disease.
This balance is achieved partly through regulatory T cells (Tregs).
CD4(+)CD25(+) Tregs are either naturally occurring or induced by
antigens and are characterized by the expression of the X-linked
forkhead/winged helix transcription factor, Foxp3. Here we report a
previously unrecognized subset of CD4(+)CD25(+) Tregs derived from
CD4(+)CD25(-) T cells induced by nitric oxide (NO). The induction of
Tregs (NO-Tregs) is independent of cGMP but depends on p53, IL-2, and
OX40. NO-Tregs produced IL-4 and IL-10, but not IL-2, IFNgamma, or
TGFbeta. The cells were GITR(+), CD27(+), T-bet(low), GATA3(high), and
Foxp3(-). NO-Tregs suppressed the proliferation of CD4(+)CD25(-) T
cells in vitro and attenuated colitis- and collagen-induced arthritis
in vivo in an IL-10-dependent manner. NO-Tregs also were induced in
vivo in SCID mice adoptively transferred with CD4(+)CD25(-) T cells in
the presence of LPS and IFNgamma, and the induction was completely
inhibited by N(G)-monomethyl-l-arginine, a pan NO synthase inhibitor.
Therefore, our findings uncovered a previously unrecognized function
of NO via the NO-p53-IL-2-OX40-survivin signaling pathway for T cell
differentiation and development.
PMID: 17875988
And now we're back at IL-10....
So go to my next post today for DUSP10 and MKP5..... :)
What thread does that get posted in?
Think i'll try the psoriasis 2007 II thread?
randall.... looking very CLEAR today... due to NAG NO less....
manfred
> Fucoidan is an important addition to the body's virus-combating
> arsenal. It is produced from Fucus versiculosus <sniP>
Rating: Hold Off
Supplement U-Fn ( U-fucoidan)
U-Fn appears to be a poor value as it is very expensive and there is
no evidence showing benefits on human subjects
>
> Why would a person whose _genetically_ skewed to the Th1 side, need
> anything of this
> nature? Most psoriatics don't get as many aliments as the population
> at
> large as a result of the Th1 skew, provided their lifestyle is fairly
> healthy. Like
> JX's for example. Or mine...
I don't know abou anyone else but I have a my share of viral and
bacterial infections including repeated bouts of strep throat as a
kid. I believe that is why I have the severity of P I do today.
> What keeps the psoriatic Th1 skewed in the first place is LPS
> (endogenous endotoxins).http://groups.google.com/groups/search?q=lps+randall+psoriasis&qt_s=S...
Which takes us back to NO.
http://www.pnas.org/cgi/content/full/99/25/16186
Nitric oxide preferentially induces type 1 T cell differentiation by
selectively up-regulating IL-12 receptor 2 expression via cGMP
Discussion
[note the ***]
A strong, immune regulatory role for NO has long been recognized (25,
26). Earlier studies showed that mice ***deficient in NO developed
enhanced Th1 response after infections and antigenic
stimulation,*** producing more IFN- and less IL-4 compared with
similarly treated, intact mice (27-29). These observations indicated
that NO selectively inhibits the expansion of Th1 cells by a negative-
feedback mechanism. This is achieved, at least in part, by the
selective inhibition of IL-12 synthesis by activated macrophages (30).
This mechanism potentially would be highly beneficial during
inflammatory diseases predominantly mediated by type 1 cells. In
contrast, a strong type 1 T cell response is highly desirable for an
effective host defense against intracellular pathogens. This could be
enhanced and accelerated by low concentrations of NO provoked during
the early stage of infection (19). Thus, immunologically, NO may have
evolved to fine-tune the immune homeostasis in health and disease.
Data presented here significantly advance this concept by providing a
mechanistic explanation for the selective enhancing effect of low
doses of NO on type 1 T cell differentiation. In the present study, we
used NOC-18 as an NO donor, which, at 5-20 µM, constantly released 10-
40 nM NO and a half-life of 20 h (31, 32). At these concentrations, NO
has no detectable effect on the apoptosis of T cells. Because
apoptosis would not be expected to be type 1 T cell-specific, this is
consistent with our finding that NO, at these concentrations, has
little or no effect on the differentiation of Th2 cells. Instead, our
results clearly demonstrate that ***low doses of NO preferentially
promoted type 1 T cell differentiation by selective induction of
IL-12R 2 via cGMP.*** The effect of NO on T cell activation is
likely to be immediate. Elevated levels of cGMP, corresponding to
enhanced Th1 cell activation, were detected in CD4+ T cells 30 min
after the cells were exposed to NO (Fig. 1b). Furthermore, CD4+ T
cells stimulated with NO for 3.5 h, and washed, produced enhanced Th1
response when subsequently cultured with antigen on APCs and IL-12.
Reports of cyclic nucleotide effects on T cell activation indicate
that cAMP is inhibitory, whereas effects of cGMP have not been
elucidated conclusively. Our results demonstrate an enhancing effect
of cGMP on T cell activation. Furthermore, we provide here the
mechanism by which cGMP selectively promotes type 1 T cell response.
It should be noted that the effect of cGMP again is dose-dependent and
is influenced by the signal by which the cells were induced to
differentiate. For Th1 cells induced with specific antigen (OVA
peptide) and APCs, low doses (125-250 µM) of 8-Br-cGMP enhanced
cellular proliferation, whereas a high dose (2,000 µM) clearly was
inhibitory. The inhibitory effect of cGMP is in agreement with
previous reports, which showed that ***high levels of cGMP, induced
by high concentrations of NO, inhibited T cell proliferation (33) by
blocking IL-2 synthesis (34).*** Furthermore, high doses of NO
(>100 µM) could inhibit cytokine production by T cells via cGMP-
dependent as well as cGMP-independent pathways, presumably involving
apoptosis (35).
Among the several factors reported to be important for inducing type 1
T cell differentiation (36-38), IL-12 clearly plays the dominant role
(17, 18). IL-12R is composed of two subunits, 1 and 2, which are
both required for high-affinity IL-12 binding and signaling (39-41).
IL-12R 1 is widely expressed in cells of hematopoietic origin, whereas
IL-12R 2 is detected selectively in cells responsive to IL-12 such as
T cells. Naïve T cells express IL-12R upon TCR engagement. The
expression of IL-12R appears to be transient and is down-regulated in
committed memory Th1 cells (42), which can be maintained and expanded
by other factors including IL-15 (43-45). However, the initial
expression of IL-12R is sustained by the presence of the innately
induced cytokine IL-18 (24). This has been used to explain the often-
observed, synergistic effect of IL-18 and IL-12 in the induction of
type 1 T cells (46, 47). Our results here demonstrate that a ***low
concentration of NO is an additional factor for enhancing IL-12R
expression and, thus, promoting type 1 cell differentiation***.
These data also explain the earlier observation that NO acted at the
inductive phase of Th1 cell development and had no effect on
established memory T cells (19).
effect on established memory T cells (19). The mechanism by which cGMP
selectively induces IL-12R 2, rather than IL-4R or IL-18R, is unclear
at present. In endothelial cells (48) and macrophages (49), ***low
concentrations of NO were shown to up-regulate and high doses of NO to
down-regulate NF B activity***. Alternatively, cGMP may act through
the P-Raf/MEK/ERK pathway. The precise mechanism(s) of the action of
low concentrations of NO in the type 1 T cell differentiation system
currently is being explored.
Our results, therefore, establish the following sequence of events,
which lead to the selective induction of type 1 T cell differentiation
by low concentrations of NO (Fig. 6). NO, produced by activated APCs
or provided exogenously in the microenvironment, activates sGC and
leads to increased cGMP production. This, then, leads to the induction
of increased IL-12R 2 expression, which facilitates the
differentiation of type 1 T cells by IL-12 and TCR engagement. IL-12
is produced by the APC or present exogenously in the microenvironment.
These findings, therefore, provide an explanation for the hitherto
puzzling but important observation that low concentrations of NO
enhance T cell , proliferation and that this enhancement is selective
for the induction of Th1 cells, but not Th2 cells, or established
memory Th1 cells. We, therefore, have revealed a pathway in which NO
represents an additional signal for the induction of T cell subset
response, thus contributing to the understanding of the increasingly
complex network of immune regulation essential for health and disease.
> The one alcholic product that seems to Help psoriasis
> used in moderation is red wine-
> high in resveratrol, i've found. And that takes us back to P53 genes.
>
> P53 and P, (71 hits)http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed&cmd=Search&Term=p5...
>
> Resveratrol and p53-- (82 hits on pubmed)
>
> REsveratrol increases/activates SirT1....
> keywords:: resveratrol sirT1 and p53 ( seven hits on pubmed)
>
> Lets look at some sirtuin 1 hits that are current.
>
> http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView...
> The Effect of Resveratrol on a Cell Model of Human Aging.
> Stefani M, Markus MA, Lin RC, Pinese M, Dawes IA, Morris BJ.
>
> School of Medical Sciences, University of Sydney, Sydney, New South
> Wales, Australia.
>
> The natural polyphenol resveratrol stimulates sirtuins and extends
> lifespan. Here resveratrol inhibited expression of replicative
> senescence marker INK4a in human dermal fibroblasts and 47 out of
> 19,000 genes from microarray experiments were differentially
> expressed. These included genes for growth, cell division, cell
> signaling, apoptosis and transcription. Genes involved in Ras and
> ubiquitin pathways, Ras-GRF1, RAC3 and UBE2D3, were downregulated. The
> changes suggest resveratrol might alter sirtuin-regulated downstream
> pathways, rather than sirtuin activity. Serum deprivation and high
> confluency caused nuclear translocation of the SIRT1-regulated
> transcription factor FOXO3a. Our data indicate resveratrol's actions
> might cause FOXO recruitment to the nucleus.
>
> PMID: 17804521
I like resveratrol. It also upregulates the Vitamin D Receptors so
used in conjuction with Vitamin D it could be a winner!
> ==========================
>
> OK? Now lets look at foxo3a & foxp3 and other forkHEADs. lol
>
> http://en.wikipedia.org/wiki/Foxp3
>
> http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView...
> Forkhead transcription factors in immunology.
> Jonsson H, Peng SL.
>
> Division of Rheumatology, Department of Internal Medicine, Washington
> University School of Medicine, 660 S. Euclid Ave., St. Louis, MO
> 63110, USA.
>
> The forkhead (Fox) gene family comprises a diverse group of "winged-
> helix" transcription factors that play important roles in development,
> metabolism, cancer and aging. Recently, several forkhead genes have
> been demonstrated to play critical roles in lymphocyte development and
> effector function, including Foxp3 in the development of regulatory T
> cells, Foxj1 and Foxo3a in the regulation of CD4+ T cell tolerance,
> and Foxn1 in thymic development. Roles for other forkhead genes have
> also been proposed, including Foxp1 in macrophage differentiation,
> Foxq1 in natural killer cell effector function and Foxd2 in T cell
> activation. Thus, forkhead genes promise insight into the mechanisms
> of immunoregulation in several immune cell lineages, and their
> dysregulation likely contributes to the pathogenesis of several
> immunological disorders, suggesting that their study will lead to the
> development of novel therapeutic agents.
>
> PMID: 15719167
>
> ------------------------------
>
> Now look at foxP3 and psoriasis.
>
> http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView...
>
> [...]
> BACKGROUND: Depletion of CD4+ CD25+ Foxp3+ naturally occurring
> regulatory T cells (T(reg)) induces autoimmune phenomena.
> [...]
> PMID: 16902287
>
> ------------------
>
> http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView...
> Immunohistochemical analysis of regulatory T cell markers FOXP3 and
> GITR on CD4+CD25+ T cells in normal skin and inflammatory dermatoses.
> de Boer OJ, van der Loos CM, Teeling P, van der Wal AC, Teunissen MB.
>
> Department of Pathology, Academic Medical Center, University of
> Amsterdam, Amsterdam, The Netherlands. o.j.deb...@amc.uva.nl
>
> Regulatory T cells (Treg) are a subset of T lymphocytes that play a
> central role in immunologic tolerance and in the termination of immune
> responses. The identification of these cells in normal and
> inflammatory conditions may contribute to a better understanding of
> underlying pathology. We investigated the expression of FOXP3 and GITR
> in normal skin and in a panel of different inflammatory dermatoses.
> Immunohistochemical double stainings in skin tissue sections revealed
> that FOXP3 and GITR were almost exclusively present on T cells ...
NO again, this time suppressing diabetes:
http://www.jimmunol.org/cgi/content/full/176/6/3449
Regulatory T Cells Can Mediate Their Function through the Stimulation
of APCs to Produce Immunosuppressive Nitric Oxide
Abstract
Regulatory T cells (Tr cells) play a critical role in inducing immune
tolerance. It remains largely unclear how various types of Tr cells
perform their regulatory function. We have studied the underlying
regulatory mechanism of a population of autoantigen-specific CD4+ Tr
cells. These T cells are specific for the glutamic acid decarboxylase
p206-220 peptide and are isolated from the diabetes-resistant nonobese-
resistant mice. Although these T cells express T-bet and display a Th1
phenotype, they are able to inhibit diabetes. Their regulatory
function is dependent on both IFN- and cell contact with target cells.
These Tr cells can mediate their cell contact-dependent regulatory
function by secreting IFN- which stimulates APCs to produce NO. NO is
necessary for the Tr cells to inhibit the proliferation of pathogenic
T cells and the development of diabetes. Therefore, we have identified
a novel mechanism by which these Tr cells can exert their regulatory
function. These results also provide an explanation as to why IFN- may
play both pathogenic and immunomodulatory roles in autoimmune
diseases.
Discussion
Autoreactive CD4+ T cells may not only function as pathogenic cells
and promote autoimmune disease progression, but they may also function
as regulatory T cells (Tr cells)3 and inhibit disease development.
Several populations of Tr cells have been identified with varied
phenotypes that play critical roles in the development of immunity and
autoimmunity (1, 2, 3, 4, 5). Defective Tr cell development or the
depletion of Tr cells in animals results in the development of
autoimmune diseases. For example, a defective population of naturally
arising Foxp3+CD4+CD25+ Tr cells (natural Tr cells) may result in an
altered balance of pathogenic and Tr cells which leads to the
development of autoimmune diseases (1, 6, 7, 8). These Tr cells that
are expanded in vitro can be used to inhibit autoimmune diseases (9,
10).
....We provide evidence demonstrating that NR206 Tr cells mediate
their cell contact-dependent regulatory function by secreting IFN-
which stimulates APCs to produce NO. NO then suppresses the
proliferation of pathogenic T cells and inhibits diabetes.
Cruiser
> > I like your folic acid theory. What else with it? Vitamin C? NAC? I
> > have been reading some stuff about high dose folic acid. Are you
> > trying it? I would like it even more if I saw you getting good
> > results!
>
> Hey! I doubled my dosage of folic acid.... I went from one or two
> 400 mcg's to up to four a day. Let's see. That would be 1.6 mg's.
>
Doses under 10mg per day are unlikely to be effective.
I recommend 15mg per day for an adult male between 180 and 200lbs.
> Now when I take it out of the mix we shall see what it does or did.
> LOL
>
Not likely to make much difference since you are not taking enough to
start with.
cruiser
Cruiser
>
> Cruiser,
> I like your folic acid theory. What else with it? Vitamin C? NAC?
You posted about Dr Paul awhile back.
Here is a response that he sent to me personally, when I wrote him an
email (before you posted)
-----------
"There are many chronic inflammatory diseases that may well be
candidates for inclusion under the NO ONOO- cycle paradigm and
psoriasis may well be one of them. I did not make a case for it in my
book, but nothing should be read into that."
-Snip-
"the <no ONOO- cycle involves increases in nitric oxide, a vasodilator
but also peroxynitrite which acts both directly and indirectly as a
vasoconstrictor. <it follows that it may act on oxygen availability
as you describe,"
------------
Highly recommend you read this:
http://www.bh4.org/pdf/das.pdf
http://www.google.ca/search?hl=en&q=folic+acid+ONOO&meta=
http://ajpheart.physiology.org/cgi/reprint/275/5/H1585.pdf
and Anna K. Brzezinska. Peroxynitrite is a contractile
agonist of cerebral artery smooth muscle cells. Am. J. Physiol.
275 (Heart Circ. Physiol. 44): H1585-H1591, 1998.-On
reperfusion of ischemic tissue, a prolonged phase of vasoconstriction
occurs, the mechanism of which is poorly understood.
However, it is known that peroxynitrite (ONOO2) is
formed during reperfusion. In this study the contractile
properties of ONOO2 were investigated in Wistar rat middle
cerebral arteries. The effects of ONOO2 on vessel diameter
were dose dependent. Low-dose ONOO2 (10 M) caused
vessels to constrict by 15%. At an intermediate concentration
of 25 M, the effect of ONOO2 was variable, whereas at the
highest concentration (100 M), vessels underwent persistent
dilation and became insensitive to the endogenous
vasoconstrictor 5-hydroxytryptamine. At the single cell level,
ONOO2 caused cerebral artery smooth muscle cells to contract.
Reduced, but not oxidized, glutathione completely
inhibited the contractile action of ONOO2 on single cells.
Vehicle and decomposed ONOO2 each had minimal effect on
cell length. These data show that ONOO2 is a contractile
agonist of middle cerebral arteries, at the single cell and
whole vessel levels, suggesting that formation of ONOO2 may
contribute mechanistically to ischemic brain injury during
stroke. Moreover, relatively high concentrations of ONOO2
result in vascular paralysis.
15mg folic acid, 1000mg vitamin C, 500mg NAC, 1 mg B12, 100mg B6, 2
mutlti-vitamins with minerals, 1 tsp Metamucil in milk.
Yummy.
Crusier
Cruiser
> I would like it even more if I saw you getting good
> results
Can't comment on results, since I have been using Dovobet for several
months.
Any and all positive results must be attributed to the medication,
don't you know.
Still, it fixes the PA in my fingers. A couple glasses of V8 Splash
Tropical Blend, during the day, sustains the benefit. AFAIK Dovobet
cannot fix PA.
cruiser.
manfred
I am sure you are aware of this old study but will post it as it is
interesting in regards to the dosage of folic acid they used:
High-dose folic acid for psoriasis - Literature Review & Commentary -
Brief Article
Townsend Letter for Doctors and Patients, May, 2003 by Alan R. Gaby
Seven patients with long-standing psoriasis were given *****20 mg
of folic acid 4 times per day.**** Marked improvements were
noted after 3-6 months of treatment. Three additional patients who had
previously received methotrexate treatment for psoriasis were also
given folic acid. In one patient, new lesions appeared all over the
trunk in places where they had never existed. One patient showed
decided worsening and the third patient improved considerably.
Comment: The rationale for using high-dose folic acid is based on the
fact that allopurinol, a xanthine oxidase inhibitor, is effective
against psoriasis. The author of the present study has found that
folio acid fortified with specific amounts of ascorbic acid (to keep
it in the reduced state as tetrahydrofolate) is also an effective
xanthine oxidase inhibitor. Although no controlled trials have been
done with folic acid, other clinicians have observed the same
beneficial effect against psoriasis that Oster reported more than a
quarter-century ago. Methotrexate interferes with folic acid
metabolism and, for reasons that are not clear, appears to cause an
adverse reaction to high-dose folic acid in some cases. However, for
patients who have not previously been treated with methotrexate, folic
acid appears to be a safe and promising therapy for chronic psoriasis.
Of course, when using high-dose folic acid, it is important to
remember that it can mask the laboratory diagnosis of pernicious
anemia.
Oster KA. A cardiologist considers psoriasis. Cutis 1977;20:39-41.
COPYRIGHT 2003 The Townsend Letter Group
COPYRIGHT 2003 Gale Group
Cruiser
>
> - Show quoted text -
20mg 4 times a day is too much.
Cruiser
randall
> On Oct 2, 2:56 pm, randall <ranhu...@aol.com> wrote:
>
> > Fucoidan is an important addition to the body's virus-combating
> > arsenal. It is produced from Fucus versiculosus <sniP>
>
>
> Rating: Hold Off
What? They don't like seaweed? LOL
> Supplement U-Fn ( U-fucoidan)
> U-Fn appears to be a poor value as it is very expensive and there is
> no evidence showing benefits on human subjects
Excuse me? I posted how many abstracts?
That would be 704 hits on pubmed. No small #.
Some of them looked rather good.
How many posts are on pubmed for MMS (miracle mineral supplement?)
Ans: Zero....
>
>
>
> > Why would a person whose _genetically_ skewed to the Th1 side, need
> > anything of this
> > nature? Most psoriatics don't get as many aliments as the population
> > at
> > large as a result of the Th1 skew, provided their lifestyle is fairly
> > healthy. Like
> > JX's for example. Or mine...
>
> I don't know about anyone else but I have a my share of viral and
> bacterial infections including repeated bouts of strep throat as a
> kid. I believe that is why I have the severity of P I do today.
And while I'm an early onset psoriatic, I never got/get sick, yet
progressively got worse (PASi)
from puberty in to my thirties. At which point it was bad enough to
cause me to
question my length of mortality. I really didn't think at the time i'd
see my kids grow
up....NOW, i'm looking forward to their progeny and quite likely
theirs. :)
>
> > What keeps the psoriatic Th1 skewed in the first place is LPS
> > (endogenous endotoxins).http://groups.google.com/groups/search?q=lps+randall+psoriasis&qt_s=S...
>
> Which takes us back to NO.
OH NO?
NO NO nO ONOO you mean? <w>
I guess you can feel my sentiments,
http://groups.google.com/groups/search?q=no+mo+psoriasis+randall&qt_s=Search
&
http://groups.google.com/groups/search?q=NO%2FONOO+psoriasis+randall&qt_s=Search
>
> http://www.pnas.org/cgi/content/full/99/25/16186
> Nitric oxide preferentially induces type 1 T cell differentiation by
> selectively up-regulating IL-12 receptor 2 expression via cGMP
>
> Discussion
> [note the ***]
I'll try....
But what happened with the bleach (chlorine) to kill the bad guys? Lol
<w>
>
> A strong, immune regulatory role for NO has long been recognized (25,
> 26). Earlier studies showed that mice ***deficient in NO developed
> enhanced Th1 response after infections and antigenic
> stimulation,***
Why didn't they get the NO? Not enough arginine? Kidding....
http://groups.google.com/groups/search?q=arginine+nitric+oxide+psoriasis+randall&qt_s=Search
OH. I see. The b-12 is required to down regulate the NO. OH NO. LOL
> producing more IFN- and less IL-4 compared with
> similarly treated, intact mice (27-29). These observations indicated
> that NO selectively inhibits the expansion of Th1 cells by a negative-
> feedback mechanism.
Maybe in theory. But what about for psoriatics?
> This is achieved, at least in part, by the
> selective inhibition of IL-12 synthesis by activated macrophages (30).
> This mechanism potentially would be highly beneficial during
> inflammatory diseases predominantly mediated by type 1 cells. In
> contrast, a strong type 1 T (Th1) cell response is highly desirable for an
> effective host defense against intracellular pathogens. This could be
> enhanced and accelerated by low concentrations of NO provoked during
> the early stage of infection (19). Thus, immunologically, NO may have
> evolved to fine-tune the immune homeostasis in health and disease.
Whats the relationship of NO to LL-37?
If LPS is uPregulating Nitric Oxide to get rid of it, then maybe the
excess ll-37 is creating the pathogenesis of psoriasis in the process
with one or two genes being the hidden culprit?
Here's some new stuff (GKE) to blunt the LPS, but work better then
LL-37, which
is toxic.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16940092&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
1: Antimicrob Agents Chemother. 2006 Sep;50(9):2983-9.
In silico identification and biological evaluation of antimicrobial
peptides based on human cathelicidin LL-37.
Sigurdardottir T, Andersson P, Davoudi M, Malmsten M, Schmidtchen A,
Bodelsson M.
Department of Anesthesiology and Intensive Care, Lund University,
Lund, Sweden.
Bacterial lipopolysaccharides (LPS) are important triggers of the
widespread inflammatory response, which contributes to the development
of multiple organ failure during sepsis. The helical 37-amino-acid-
long human antimicrobial peptide LL-37 not only possesses a broad-
spectrum antimicrobial activity but also binds and neutralizes LPS.
However, the use of LL-37 in sepsis treatment is hampered by the fact
that it is also cytotoxic. To find a less toxic analog of LL-37, we
used in silico analysis to identify amphipathic helical regions of
LL-37. A 21-amino-acid fragment _______(GKE)____________ was
synthesized, the biological actions of which were compared to those of
two equally long peptides derived from the N and C termini of LL-37 as
well as native LL-37. GKE displayed antimicrobial activity against
Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus,
Candida albicans, and Candida parapsilosis that was similar to or even
stronger than LL-37. GKE, as well as the equally long control
peptides, attracted granulocytes in a fashion similar to that of
LL-37, while only GKE was as potent as LL-37 in inhibiting LPS-induced
vascular nitric oxide production. GKE caused less hemolysis and
apoptosis in human cultured smooth muscle cells than LL-37. In
summary, we have identified an active domain of LL-37, GKE, which
displays antimicrobial activity in vitro and LPS-binding activity
similar to those of LL-37 but is less toxic. GKE therefore holds
promise as a template for the development of peptide antibiotics for
the treatment of sepsis.
PMID: 16940092
GEE! NO....
GKE.... <w>
>
> Data presented here significantly advance this concept by providing a
> mechanistic explanation for the selective enhancing effect of low
> doses of NO on type 1 T cell differentiation. In the present study, we
> used NOC-18 as an NO donor, which, at 5-20 µM, constantly released 10-
> 40 nM NO and a half-life of 20 h (31, 32). At these concentrations, NO
> has no detectable effect on the apoptosis of T cells. Because
> apoptosis would not be expected to be type 1 T cell-specific, this is
> consistent with our finding that NO, at these concentrations, has
> little or no effect on the differentiation of Th2 cells. Instead, our
> results clearly demonstrate that ***low doses of NO preferentially
> promoted type 1 T cell differentiation by selective induction of
> IL-12R 2
What, what ? what- what-what? We KNOW IL-12R is in the P pathways....
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17761156&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Cell Immunol. 2007 May;247(1):1-11. Epub 2007 Aug 29.Links
Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and
inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO
1275.
Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U.
Department of Clinical Pharmacology and Experimental Medicine,
Centocor, Inc., Malvern, PA, USA.
Cytokines interleukin (IL)-12 and IL-23 are implicated in the
pathogenesis of psoriasis. IL-12 causes differentiation of CD4+ T
cells to interferon-gamma (IFN-gamma)-producing T helper 1 (Th1)
cells, while IL-23 induces differentiation to IL-17-producing
pathogenic Th17 cells. The effects of the monoclonal antibody to
IL-12/23 p40 subunit (CNTO 1275) on IL-12 receptor (IL-12R)
expression, markers associated with skin homing, activation, and
cytokine secretion were investigated in vitro using human peripheral
blood mononuclear cells (PBMCs) from healthy donors. PBMCs were
activated in the presence or absence of recombinant human (rh) IL-12
or rhIL-23, with or without CNTO 1275. CNTO 1275 inhibited
upregulation of CLA, IL-12R, IL-2Ralpha and CD40L expression and also
inhibited IL-12- and IL-23-induced IFN-gamma, IL-17A, tumor necrosis
factor (TNF)-alpha, IL-2, and IL-10 secretion. Thus, the therapeutic
effect of CNTO 1275 may be attributed to the IL-12/23 neutralization,
resulting in decreased expression of skin homing and activation
markers, and IL-12- and IL-23-induced cytokine secretion.
PMID: 17761156
Prabby (U. Prabhakar) is definitely on the right track with cnto 1275
and IL-12...
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Prabhakar%20U%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus
> via cGMP.***
How many cGMP articles did I do?
http://groups.google.com/groups/search?q=+cgmp+psoriasis+randall&qt_s=Search
http://en.wikipedia.org/wiki/Cyclic_guanosine_monophosphate
How many guanosine articles have I done?
http://groups.google.com/groups/search?q=guanosine+psoriasis+randall&qt_s=Search
How about pure GuanO articles ... LOL
WOW
More bat guanO then I would have thought. lOL
http://groups.google.com/groups/search?q=guano+psoriasis+randall&qt_s=Search
Since we're on this line of thinking it brings up
ANF....
http://en.wikipedia.org/wiki/Atrial_natriuretic_factor
This is weird. I figured more for ANF...
http://groups.google.com/groups/search?q=Atrial+natriuretic+factor+psoriasis+randall&qt_s=Search
Didn't I post a bunch of Kiemer's abstracts? They must all be in the
above link....
WE only pick up one more post droPPing factor from the keywords,
http://groups.google.com/groups/search?q=Atrial+natriuretic+psoriasis+randall&qt_s=Search
Let's see what's current for Kiemer.
> The effect of NO on T cell activation is
> likely to be immediate. Elevated levels of cGMP, corresponding to
> enhanced Th1 cell activation, were detected in CD4+ T cells 30 min
> after the cells were exposed to NO (Fig. 1b). Furthermore, CD4+ T
> cells stimulated with NO for 3.5 h, and washed, produced enhanced Th1
> response when subsequently cultured with antigen on APCs and IL-12.
> Reports of cyclic nucleotide effects on T cell activation indicate
> that cAMP is inhibitory, whereas effects of cGMP have not been
> elucidated conclusively.
What? This is also a NO BRAINER.
CgmP is BAD....
Same with calcium ions...
Let's see:
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=14690334&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Defective cyclic guanosine monophosphate-gated calcium channels and
the pathogenesis of psoriasis.
McKenzie RC, Oda Y, Szepietowski JC, Behne MJ, Mauro T.
Epidermal Inflammation and Protection Group, Department of
Dermatology, University of Edinburgh, Edinburgh, Scotland, UK.
Roddie....@ed.ac.uk
A positive association between intake of calcium channel blockers and
psoriasis has been observed recently. Intake of blockers of voltage-
gated calcium ion channels is associated with outbreaks of psoriasis
after a latent period in patients with and without a previous family
history of psoriasis. This suggests that interfering with calcium
influx may trigger psoriasis. Calcium influx also occurs via cyclic
guanosine monophosphate-gated channels; human keratinocytes contain
functional and non-functional (splice variants) versions of these
channels. We show here that keratinocytes and skin from psoriatic
individuals express higher levels of mRNA encoding a non-functional
cyclic guanosine monophosphate-gated calcium channel and that high
expression of the splice variant by transfection of cells in culture
leads to loss of protein expression for the functional cyclic
guanosine monophosphate-gated Ca2+ channels.
PMID: 14690334
----------------
Even goes back to arachidonic acid and hete...
http://www.nature.com/jid/journal/v74/n4/abs/5616032a.html
Keywords:: cyclic guanosine monophosphate psoriasis (46 hits on
pubmed.com)
You tell me if you think for two seconds that C-gmp isn't triggering
negative
pathways for psoriasis proliferations.
> Our results demonstrate an enhancing effect
> of cGMP on T cell activation. Furthermore, we provide here the
> mechanism by which cGMP selectively promotes type 1 T cell response.
> It should be noted that the effect of cGMP again is dose-dependent and
> is influenced by the signal by which the cells were induced to
> differentiate. For Th1 cells induced with specific antigen (OVA
> peptide) and APCs, low doses (125-250 µM) of 8-Br-cGMP enhanced
> cellular proliferation, whereas a high dose (2,000 µM) clearly was
> inhibitory. The inhibitory effect of cGMP is in agreement with
> previous reports, which showed that ***high levels of cGMP, induced
> by high concentrations of NO, inhibited T cell proliferation (33) by
> blocking IL-2 synthesis (34).***
And is therefore BAD...as far as a psoriatic is concerned....
> Furthermore, high doses of NO
> (>100 µM) could inhibit cytokine production by T cells via cGMP-
> dependent as well as cGMP-independent pathways, presumably involving
> apoptosis (35).
>
> Among the several factors reported to be important for inducing type 1
> T cell differentiation (36-38), IL-12 clearly plays the dominant role
> (17, 18). IL-12R is composed of two subunits, 1 and 2, which are
> both required for high-affinity IL-12 binding and signaling (39-41).
> IL-12R 1 is widely expressed in cells of hematopoietic origin, whereas
> IL-12R 2 is detected selectively in cells responsive to IL-12 such as
> T cells. Naïve T cells express IL-12R upon TCR engagement. The
> expression of IL-12R appears to be transient and is down-regulated in
> committed memory Th1 cells (42), which can be maintained and expanded
> by other factors including IL-15 (43-45). However, the initial
> expression of IL-12R is sustained by the presence of the innately
> induced cytokine IL-18 (24). This has been used to explain the often-
> observed, synergistic effect of IL-18 and IL-12 in the induction of
> type 1 T cells (46, 47). Our results here demonstrate that a ***low
> concentration of NO is an additional factor for enhancing IL-12R
> expression and, thus, promoting type 1 cell differentiation***.
Then their saying LOW and high NO is good. I'm not getting these guys.
There must be an ideal metabolic level of NO in relationship to what's
consumed.
http://en.wikipedia.org/wiki/Metabolism
> These data also explain the earlier observation that NO acted at the
> inductive phase of Th1 cell development and had no effect on
> established memory T cells (19).
>
> effect on established memory T cells (19). The mechanism by which cGMP
> selectively induces IL-12R 2, rather than IL-4R or IL-18R, is unclear
> at present. In endothelial cells (48) and macrophages (49), ***low
> concentrations of NO were shown to up-regulate and high doses of NO to
> down-regulate NF B activity***.
Once again. It sounds counterintuitive....Is there a negative
regulator here?
Or some homeostatic ideal?
http://en.wikipedia.org/wiki/Autocrine
&
http://en.wikipedia.org/wiki/Homeostasis
> Alternatively, cGMP may act through
> the P-Raf/MEK/ERK pathway. The precise mechanism(s) of the action of
> low concentrations of NO in the type 1 T cell differentiation system
> currently is being explored.
Ya think? LOL
Oh crap...
Did this get cut off?
randall.... i'll go back and look at this thing...
randall
OK....
Then i'll upregulate the B-12 to one mg and the B-6 with B-9 (folic
acid) to
around 5 mg's.....
See:
http://www.lef.org/magazine/mag2005/mar2005_report_folic_01.htm
http://www.lef.org/magazine/mag2005/mar2005_report_folic_02.htm
=====================
But first I have to finish the trials i'm currently doing....and I'm
pretty
clear right now... :)
So. That means I have to go backwards....which shouldn't be to hard
with all the holiday inflammatory increasing foods on the Plate....
<w>
randall...
randall
How much are you doing and what are your results?
When I went from B-9 (folic acid) 400-800 mcg's per day to twice that,
it seemed to
help for a few days. But i'm rather clear and it's hard to tell.
randall...
manfred
> On Oct 3, 4:59 pm, manfred <manfre...@lycos.com> wrote:
> > The effect of NO on T cell activation is
> > likely to be immediate. Elevated levels of cGMP, corresponding to
> > enhanced Th1 cell activation, were detected in CD4+ T cells 30 min
> > after the cells were exposed to NO (Fig. 1b). Furthermore, CD4+ T
> > cells stimulated with NO for 3.5 h, and washed, produced enhanced Th1
> > response when subsequently cultured with antigen on APCs and IL-12.
> > Reports of cyclic nucleotide effects on T cell activation indicate
> > that cAMP is inhibitory, whereas effects of cGMP have not been
> > elucidated conclusively.
>
> What? This is also a NO BRAINER.
>
> CgmP is BAD....
It's a no brainer--not as simple as you imply.
> You tell me if you think for two seconds that C-gmp isn't triggering
> negative
> pathways for psoriasis proliferations.
>
> > Our results demonstrate an enhancing effect
> > of cGMP on T cell activation. Furthermore, we provide here the
> > mechanism by which cGMP selectively promotes type 1 T cell response.
> >The inhibitory effect of cGMP is in agreement with
> > previous reports, which showed that ***high levels of cGMP, induced
> > by high concentrations of NO, inhibited T cell proliferation (33) by
> > blocking IL-2 synthesis (34).***
>
> And is therefore BAD...as far as a psoriatic is concerned....
I think you are misunderstanding this study.
"It should be noted that the effect of cGMP again is dose-dependent
and
is influenced by the signal by which the cells were induced to
differentiate. For Th1 cells induced with specific antigen (OVA
peptide) and APCs, low doses (125-250 µM) of 8-Br-cGMP enhanced
cellular proliferation, whereas a high dose (2,000 µM) clearly was
inhibitory."
Low cGMP=proliferation
High Dose cGMP=inhibition
" high concentrations of NO, inhibited T cell proliferation (33) by
blocking IL-2 synthes"
Levels of sIL-2R showed a strong correlation with the psoriasis area
and severity index (PASI). Clin Exp Immunol. 1991 August
These results suggest that the genetic polymorphisms of IL-2 and IL-4
genes can be susceptible to psoriasis in Korean, especially late-onset
psoriasis group. PMID: 17714919
We want to block IL-2 which would therefore be GOOD as far as P is
concerned.
> > Furthermore, high doses of NO
> > (>100 µM) could inhibit cytokine production by T cells via cGMP-
> > dependent as well as cGMP-independent pathways, presumably involving
> > apoptosis (35).
>
> > Among the several factors reported to be important for inducing type 1
> > T cell differentiation (36-38), IL-12 clearly plays the dominant role
> > (17, 18). IL-12R is composed of two subunits, 1 and 2, which are
> > both required for high-affinity IL-12 binding and signaling (39-41).
> > IL-12R 1 is widely expressed in cells of hematopoietic origin, whereas
> > IL-12R 2 is detected selectively in cells responsive to IL-12 such as
> > T cells. Naïve T cells express IL-12R upon TCR engagement. The
> > expression of IL-12R appears to be transient and is down-regulated in
> > committed memory Th1 cells (42), which can be maintained and expanded
> > by other factors including IL-15 (43-45). However, the initial
> > expression of IL-12R is sustained by the presence of the innately
> > induced cytokine IL-18 (24). This has been used to explain the often-
> > observed, synergistic effect of IL-18 and IL-12 in the induction of
> > type 1 T cells (46, 47). Our results here demonstrate that a ***low
> > concentration of NO is an additional factor for enhancing IL-12R
> > expression and, thus, promoting type 1 cell differentiation***.
>
> Then their saying LOW and high NO is good. I'm not getting these guys.
I believe they are saying LOW NO is bad but HIGH NO is good!
> There must be an ideal metabolic level of NO in relationship to what's
> consumed.http://en.wikipedia.org/wiki/Metabolism
>
> > These data also explain the earlier observation that NO acted at the
> > inductive phase of Th1 cell development and had no effect on
> > established memory T cells (19).
> >The mechanism by which cGMP
> > selectively induces IL-12R 2, rather than IL-4R or IL-18R, is unclear
> > at present. In endothelial cells (48) and macrophages (49), ***low
> > concentrations of NO were shown to up-regulate and high doses of NO to
> > down-regulate NF B activity***.
>
> Once again. It sounds counterintuitive....Is there a negative
> regulator here?
What's so tough here?
LOW NO induces Th1, cGMP, IL-12.
LOW NO upregulates NFkappaB while HIGH NO down-gregulates NFkappaB
Yup--you forgot to critique how "NO is necessary for the Tr cells to
inhibit the proliferation of pathogenicT cells and the development of
diabetes...
randall
So? We need more NO?
You could sniff your cars tailpipe? Cheaper then taking arginine
suPPlements.
http://en.wikipedia.org/wiki/Nitric_oxide
I'm not quite sure of the dosage.
May prevent heart attacks as well. LOL
http://en.wikipedia.org/wiki/Endothelium-derived_relaxing_factor
[...]
Green, leafy vegetables and some root vegetables (such as beetroot)
have high concentrations of nitrate. When eaten and absorbed into the
bloodstream nitrate is concentrated in saliva (about 10 fold) and is
reduced to nitrite on the surface of the tongue by a biofilm of
commensal facultative anaerobic bacteria. <sniP>
--------------
Greens....
Certainly less intrusive then tailpipes.
-----
Of course ONOO- (Peroxynitrite ) is still a problem.
http://en.wikipedia.org/wiki/Peroxynitrite
Bring in the chinese mustard?
http://en.wikipedia.org/wiki/Brassica_juncea
Those greens and mustards have worked well enough for me.
http://groups.google.com/groups/search?qt_s=1&q=Peroxynitrite+juncea+psoriasis
-----------------------
Vitamin C may work as well also. Let's look...
-----
Of course, proper diet and exercise can't be beat...
-----
If you have a better idea, i'm all ears..... and very very little
flaky skin. <w>
randall...
manfred
"Arginase I is constitutively expressed and
arginase II is induced by endotoxin"
Arginase inhibits NO
"When we competed for L-arginine influx via the cationic
amino acid transporters by addition of L-lysine, we find a 60-70%
inhibition of arginase activity without significant loss of NOS-2
activity. Addition of L-valine, as an arginase inhibitor, leads to a
25% increase in NO formation and an 80-90% decrease in arginase
activity."
"Asc supplementation combined with arginase inhibition, to increase
L-arginine availability"
"One of the most promising research directions deals with the
administration of citrulline as a more efficient alternative to
arginine, especially against underlying splanchnic sequestration
of amino acids."
Here's a couple more I just found:
in pulmonary arterial endothelial cells ...treatment with L-Val
decreased urea production and increased NO production. Treatment with
L-Arg increased both urea and NO production. The addition of the
combination L-Arg and L-Val decreased urea production compared with
the addition of L-Arg alone and increased NO production compared with
L-Val alone. PMID: 14977627
Randall, you've got this one covered--
... High levels of arginase and ornithine in different carcinomas may
indicate their relation to cancer. Carnitine is a cofactor required
for the transformation of free long-chain fatty acids into acetyl-
carnitines. We have examined the protective effect of carnitine and
the possibility that it disturbs arginase-nitric oxide (NO)
interaction.... Tissue arginase activity and ornithine levels
decreased significantly with carnitine. NO levels were significantly
higher in the treatment group. One of the possible mechanisms of
carnitine's protective role in tumour progression might be its
promotion of NO. This mechanism could decrease the production of
tumour-promoting agents, polyamines, and increase the production of
NO, thereby exerting a protective effect on cancer development.
PMID: 17689108 [PubMed - in process]
Conversely:
...RESULTS: NAC had an increasing effect on both of liver and kidney
tissue arginase activities and ornithine levels while decreasing
plasma NO concentration. CONCLUSION: The stimulatory effect of NAC on
arginase activity may result in an inhibition of the plasma NO
level...PMID: 15458774
No butt kissing required! It's too early to tell how the NCX 1022
nitric oxide donater will do. (Psoriasis 2007 II)
randall
>
> "Arginase I is constitutively expressed and
> arginase II is induced by endotoxin"
>
> Arginase inhibits NO
>
> "When we competed for L-arginine influx via the cationic
> amino acid transporters by addition of L-lysine, we find a 60-70%
> inhibition of arginase activity without significant loss of NOS-2
> activity. Addition of L-valine, as an arginase inhibitor, leads to a
> 25% increase in NO formation and an 80-90% decrease in arginase
> activity."
Good tiP.... how much lysine and valine are you taking?
I've modified my personal regimen the last few days as a result of
increasing the folic acid from less then a mg to over 4-6 mg.s a day.
>
> "Asc supplementation combined with arginase inhibition, to increase
> L-arginine availability"
>
> "One of the most promising research directions deals with the
> administration of citrulline as a more efficient alternative to
> arginine, especially against underlying splanchnic sequestration
> of amino acids."
>
> Here's a couple more I just found:
>
> in pulmonary arterial endothelial cells ...treatment with L-Val
> decreased urea production and increased NO production. Treatment with
> L-Arg increased both urea and NO production. The addition of the
> combination L-Arg and L-Val decreased urea production compared with
> the addition of L-Arg alone and increased NO production compared with
> L-Val alone. PMID: 14977627
Arginine/ornithine seemingly were agonistic for p severity in my early
trials
going back to mid 80's....
>
> Randall, you've got this one covered--
>
> ... High levels of arginase and ornithine in different carcinomas may
> indicate their relation to cancer. Carnitine is a cofactor required
> for the transformation of free long-chain fatty acids into acetyl-
> carnitines. We have examined the protective effect of carnitine and
> the possibility that it disturbs arginase-nitric oxide (NO)
> interaction.... Tissue arginase activity and ornithine levels
> decreased significantly with carnitine. NO levels were significantly
> higher in the treatment group. One of the possible mechanisms of
> carnitine's protective role in tumour progression might be its
> promotion of NO. This mechanism could decrease the production of
> tumour-promoting agents, polyamines, and increase the production of
> NO, thereby exerting a protective effect on cancer development.
> PMID: 17689108 [PubMed - in process]
Note... to me.. go back and review this link,
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=carnitine%20nitric%20oxide
>
> Conversely:
>
> ...RESULTS: NAC had an increasing effect on both of liver and kidney
> tissue arginase activities and ornithine levels while decreasing
> plasma NO concentration. CONCLUSION: The stimulatory effect of NAC on
> arginase activity may result in an inhibition of the plasma NO
> level...PMID: 15458774
I'd love to leverage my NAC usage... sometimes it works great...Others
nada...
>
> No butt kissing required! It's too early to tell how the NCX 1022
> nitric oxide donater will do. (Psoriasis 2007 II)
Lets try this from now on...
http://pmid.us/
And then add your pmid and any terms..
So
http://pmid.us/psoria*+nitric+oxide
Did it work?
randall... keePing my fingers crossed and amino acids balanced to
lower Arg II ?
randall
>
> Lets try this from now on...
http://pmid.us/
>
> And then add your pmid and any terms..
>
> So
>
> http://pmid.us/psoria*+nitric+oxide
>
> Did it work?
Yep... worked great. At least now we can find all pubmed
cites with keywords we're interested in...
Here's the page to go with
http://pmid.us/
-----------------------
Link to medical articles on PubMed using PMIDs (PubMed Identifiers)
For example, this links to the abstract for PMID 12748199:
http://pmid.us/12748199
Compare that to the equivalent but much longer direct link to PubMed:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=12748199&dopt=AbstractPlus
(Learn more about linking directly to PubMed.)
Examples:
*
Get abstracts for both PMID 2676911 and PMID 6189501:
http://pmid.us/2676911+6189501
*
Get the full text article for PMID 10221304:
http://pmid.us/full:10221304
Full text retrieval priority: PMC > publisher (free) >
FindArticles > publisher (fee) > abstract
*
Get related articles for PMID 10221304:
http://pmid.us/rel:10221304
*
Search for anything (you must escape non-url-friendly
characters):
http://pmid.us/alopecia+minoxidil
http://pmid.us/(alopecia+OR+baldness+OR+%22hair+loss%22)+AND+(tnf-alpha+OR+tgf-beta)
All searches are performed by the US National Library of Medicine
(NLM) and PubMed.
Pmid.us is not affiliated with PubMed, FindArticles, the US National
Library of Medicine (NLM),
National Institutes of Health (NIH), or National Center for
Biotechnology Information (NCBI).
© 2007 pmid.us.
---------------------------------------------
>
> randall... keePing my fingers crossed and amino acids balanced to
> lower Arg II ?
Did i get it? maybe the science but not the Pasi lowering? LOL
Block ARG, block TNF-a, send the wide receivers long, fake the pass
and
run uP the middle...
randall... fall is on my mind, clear skin on new years day comes
first.
manfred
infections/flu in general rather than for Psoriasis, specifically. I
thought it was interesting especially with cold and flu season just
around the corner.
http://www.naturopathydigest.com/archives/2007/jan/schor.php
manfred
Grouppe Kurosawa Natural Medicines Public Blog
Today, October 29, 2007, 10 hours ago
Can Flax Lignans Control the Spread of HIV Infections?
Today, October 29, 2007, 10 hours ago | Dr. Steve
This essay is reposted from our subscription blog in the public
interest.
Flax and other seed lignans are very powerful anti-cancer agents.
However, they may also be extremely effective against viral
infections, including HIV, hepatitis B and C, and influenza. I know it
sounds too good to be true, but there is scientific evidence that it
probably is true.
In September of this year, a scientific study was finally published
showing how the lignan enterolactone killed highly malignant prostate
cancer cells. First and foremost, this lignan disrupted the
mitochondrial membrane resulting in the release of cytochrome C, the
first step in apoptosis. Second, it decreased the activity of AKT, a
critical survival factor for cancer cells, while increasing the level
of P53, the most important tumor suppressor in the body.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&
dopt=Abstract&list_uids=17876055&itool=pubmed_docsum
The AKT enzyme, activated by PI-3K signaling, is fundamentally
involved in the replication of the HIV virus in both CD4 T cells and
macrophages. The inhibition of this pathway blocks viral infection
post viral entry into cells.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&
dopt=Abstract&list_uids=12551992&itool=pubmed_docsum
AKT phosphorylates and activates the genetic factor NF-kappaB, a known
activator of the HIV gene.
P53, on the other hand, induces apoptosis in virally infected cells.
When viruses enter cells, they stimulate the production of alpha and
beta interferon, the immune hormones that block the spread of viral
infections in cells. A few years ago, alpha and beta interferons were
found to stimulate the synthesis of p53, the best known tumor
suppressor in the body. P53 induces apoptosis in virally infected
cells. This is EXACTLY what you want; otherwise these viral reservoirs
continue to make and secrete viruses into the tissues spaces resulting
in the infection of new cells.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&
dopt=Abstract&list_uids=12872134&itool=pubmed_docsum
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&
dopt=Abstract&list_uids=12957282&itool=pubmed_docsum
The following is a short, clear review article on this critically
important topic which can be read online.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&
dopt=Abstract&list_uids=12942081&itool=pubmed_docsum
A strain of mouse that genetically over expresses p53 is largely
resistant to viral infections. This further confirms that the
induction of p53 synthesis and/or activity is critically important in
controlling the spread of viral infections.
http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&
dopt=Abstract&list_uids=17726827&itool=pubmed_docsum
Flax lignans do not stimulate the synthesis of p53, but they do
increase the expression of p53 by blocking its degradation in the
cell.
I would like to see standardized flax lignans tested under control
conditions in humans with HIV infections. I am working with a medical
organization who claims great success in Africa treating HIV infected
people with a special high lignan flax extract. This sounds
ridiculous, but scientifically it is completely possible. We'll see..
Stay tuned...
Grouppe Kurosawa. Medicine in the Public Interest
manfred
http://phaelosopher.wordpress.com/2007/09/09/no-miracle-just-wonderful-chemistry/#comment-2180
Testimoinials (scroll down):
http://www.healthsalon.org/feed/
If P does have a infectious element or is triggered by a fungus as
some believe, this stuff could possibly clear it up. Ya think?
randall
Your page leads to,
http://phaelosopher.wordpress.com/2007/10/30/thoughts-on-health-and-healing-alternative-psoriasis-awareness/
Sorry. Not buying it, I tried MMS & it didn't produce anything, in
many different trials anyway.
It does crack me up when they pretend to actually know something, as
phaelosopher propounds.
If the alkaline thing works for any psoriatics it's not for the
reasons or methods put forward. The person is guessing, hubris and
chutzpah comes to mind for phaelosopher.
He'd have my attention if he simply admitted he didn't have a clue.
>
> Testimonials (scroll down):
>
> http://www.healthsalon.org/feed/
>
> If P does have a infectious element or is triggered by a fungus as
> some believe, this stuff could possibly clear it up. Ya think?
Which testimonial are you referring to?
Any that has to do with MMS? The crohn's link?
Once again, i'm not buying any of it.
The good flora implant and diet works and none of them seem to be on
board.
randall.
manfred
> On Nov 3, 10:05 pm, manfred <manfre...@lycos.com> wrote:
>
> > For more on MMS
>
> >http://phaelosopher.wordpress.com/2007/09/09/no-miracle-just-wonderfu...
> Sorry. Not buying it, I tried MMS & it didn't produce anything, in
> many different trials anyway.
Are you sure you're not thinking of MSM (Methylsulfonylmethane)?
This is the Chlorine Dioxide potion.
Snipets:
"The MMS solution is 28% sodium chlorite in distilled water. You can
produce chlorine dioxide with a single drop, when an "activator" of
vinegar, lemon juice, or a 10% solution of citric acid is added. "
"Let's talk a bit more about how and why chlorine dioxide works for
giving the immune system a new lease on life.
Volatility is what makes chlorine dioxide so effective when it
contacts pathogens. As we've mentioned, chlorine dioxide is a safe and
effective disinfectant in many municipal water delivery systems,
hospitals, and even in bioterrorism response. It stands to reason that
chlorine dioxide would be just as effective working in the waters of
the human body.
Chlorine dioxide's extreme volatility prevents pathogens from
developing a resistance. Mainly because when they "clash," the
pathogens no longer exist. Yet, healthy cells and beneficial bacteria
are unaffected.
While normal levels of oxygen in the blood cannot destroy all of the
pathogens present under disease conditions, delivery of chlorine
dioxide changes everything."
"The most salient point to know, is that chlorine dioxide has 100
times more energy to do what oxygen normally does, and yet, will not
harm healthy cells."
> Your page leads to,
>http://phaelosopher.wordpress.com/2007/10/30/thoughts-on-health-and-h...
I wasn't referring to that page, but it is interesting also.
Cruiser, take note:
"My Take on Psoriasis
Psoriasis is but one thing that can happen when not enough oxygen gets
into the blood cells. Oxygen is delivered through respiratory
function, and through hydration. In addition to life itself, our
health is dependent on sufficient quantities of oxygen being delivered
to each cell...."
>
>
> > Testimonials (scroll down):
>
> >http://www.healthsalon.org/feed/
>
> > If P does have a infectious element or is triggered by a fungus as
> > some believe, this stuff could possibly clear it up. Ya think?
>
> Which testimonial are you referring to?
>
> Any that has to do with MMS? The crohn's link?
MMS and COPD - Testimonial No 10
MMS and Dental Infection - Testimonial No. 9
MMS and Enlarged Thyroid Nodules - Testimonial No. 8
MMS - Sodium Chlorite New Treatment for Cancer, HIV and Malaria
MMS Testimonial No. 7 - Sjogren's Disease
MMS Testimonial No. 5 Diverticulitis
MMS Testimonial No. 4 - Possible Morgellon's or Other Parasitic
Disease
MMS Testimonial No. 6 - Crohn's Disease and Parasites
Chlorous Acid Study in Treating Veterinary Mastitis
Jim Humble Answers questions on the use of MMS
MMS - Sodium Chlorite - video of Malaria being cured in African Clinic
Jim Humble's Book in Hardback - Miracle Mineral Supplement of the 21st
Century
Thomas Lee Hesselink, MD writes on MMS and Sodium Chlorite - the best
science pages on MMS and Oxidative Science
Jim Humble's Malaria Solution - MMS- link to the Malaria Solution
Sodium Chlorite Cures Gut Infection
MMS Testiomonials about Parasites and Morgellon's Disease, Fiber
Disease
Jim Humble - discoverer of MMS. Radio Interview with Adam Abraham on
MMS
MMS Testimonial No. 5 - Hanneke's experience - dental infections
MMS - Sodium Chlorite - a cure for Malaria, Many Cancers, Bacterial
Infections and Viral Infections.
etc, etc, etc....
> Once again, i'm not buying any of it.
> The good flora implant and diet works and none of them seem to be on
> board.
>
> randall.
How about keeping an open mind to other possibilities?
Humira works for me but I wouldn't say it is the only way to go and am
open to other methods, including yours, Randall.
randall
> On Nov 4, 1:40 am, randall <ranhu...@aol.com> wrote:
>
> > On Nov 3, 10:05 pm, manfred <manfre...@lycos.com> wrote:
>
> > > For more on MMS
>
> > >http://phaelosopher.wordpress.com/2007/09/09/no-miracle-just-wonderfu...
> > Sorry. Not buying it, I tried MMS & it didn't produce anything, in
> > many different trials anyway.
>
> Are you sure you're not thinking of MSM (Methylsulfonylmethane)?
Your right.. I sPaced.
I have zero idea on the chlorine mixture.
My BAD... It was late last night and I jumped to the wrong idea
before thoroughly examining the page.
If you use it Cruiser please post your RESULTs....
So we're not left hanging in the DARK.
Sorry again. I had sulfur on the brain. Not chlorine.
>
> > Once again, i'm not buying any of it.
> > The good flora implant and diet works and none of them seem to be on
> > board.
>
> > randall.
>
> How about keeping an open mind to other possibilities?
Thanks for helping me keep it open. <w>
> Humira works for me but I wouldn't say it is the only way to go and am
> open to other methods, including yours, Randall.
I'm keeping my mind open... and my eyes on the MMS.
randall
manfred
manfred
description of the product.
Ebay: cgi.ebay.com/MMS-Miracle-Mineral-Supplement-5-5-oz-Original-
Formula_W0QQitemZ230196143395QQihZ013QQcategoryZ11776QQssPageNameZWDVWQQrdZ1QQcmdZViewItem
MMS Testimonial No. 14 - a Cautionary Note
27th November 2007 by Rett Anderson Posted in Disease, Cardiovascular,
Infections, MMS Testimonials
Something to take in consideration;
The stuff in question is 'MMS' or 'Miracle Mineral Supplement' which
is a 28% solution of Sodium Chlorite, which is activated by
interaction with acetic acid or citric acid, then is ingested and
becomes Chlorine Dioxide in the body.
This stuff is ENORMOUSLY powerful and unfortunately, can be DANGEROUS
by virtue of the fact that it can strip arterial plaque out so fast
that it doesn't allow any time for healing of those arteries.
How do I know? Because I've done it, and am having heart trouble right
now because of it. This is not a negative post. Before launching into
this, do not do so without getting and reading the second book, where
the author does warn about this very thing. I didn't understand. Now I
do.
Before doing this, if you have the slightest notion that you may have
any heart troubles, or even if you're older than 30, build yourself up
first with a full range of L-Ascorbic Acid and natural Vitamin C
containing products like Acerola Powder, and/or eat a lot of citrus
fruit if you can handle it, for at least 2 weeks previous to taking
MMS.
Also load yourself with potassium and magnesium first.
Once you start MMS, it *may* destroy Vitamin C in your system, so it
may be best to take MMS only once a day, and take the C products on
the other 12 hour side. C in the morning, MMS at night.
MMS can induce the most extreme of Herxheimer reactions. I have bought
activated charcoal and have Bentonite Clay on hand to deal with the
Herx when I have my next run at MMS, which won't be for another week
at least, maybe longer.
Now to the specifics of how MMS can 'cause' heart trouble:
The arteries of the heart, the ones that deliver blood from the heart
to the heart, those arteries collapse with every heartbeat. Without
enough vitamin C and collagen*, they weaken at the stress points. The
body packs cholesterol onto these weak places. The cholesterol becomes
pathogen infested and turns into plaque. Chlorine Dioxide attacks and
strips this plaque, exposing the weakened arterial wall beneath. Then
you have problems. All of this is in book two, but perhaps not warned
about harshly enough.
(*I have just started taking 'Super Collagen' by Neocell, and it also
seems to help my heart.)
In just a very few days, MMS exposed and killed a large infection in
my right sinuses. I knew I had it but I had no idea how truly bad it
was until the MMS went after it.
Don't jump into this with both feet and go splashing around. Don't be
stupid like me, and a few others. MMS is great stuff, but so powerful
that you must use caution with it.
Now, don't anybody get all worried about me. I'm fine. This has been a
learning experience for me and I do believe I'm going to emerge from
this even stronger. I sure am smarter already ;>)
xxxxxxx
PS- Somebody is going to come back and say 'I'll never take that.'
Well, I am going to take it again. This is in no way to be construed
as anti-MMS. It's just a caution." http://www.healthsalon.org/367/mms-testimonial-no-14-a-cautionary-note/
randall
> MMS again. This Ebay site has some good links to check out in the
I didn't take the time to look at the ebay product. Your link needed
medical aid. LOL
We can look at another heart felt culprit in this pathway.
Chlamydia and your immunity
http://news.biocompare.com/newsstory.asp?id=205565
[...]
Chlamydia pneumoniae is a microbe that normally causes pneumonia and
bronchitis, but it has long been associated with atherosclerosis, a
cardiovascular disease also called "hardening of the arteries."
"It was a frightening prospect," says Azenabor, "that atherosclerosis
could come from a bacterial infection." He decided to look for an
explanation.
Chlamydiae are unusual, says the Nigerian-born scientist, because,
unlike most other bacteria, they use the same form of cholesterol for
metabolism that human cells use. Chlamydiae also are intracellular
pathogens, meaning that they can only grow and reproduce inside of
another cell.
But these bacteria have another peculiar ability.
Normally, when a pathogen invades human tissue, the immune response
unleashes "killer cells" called macrophages, which stretch to engulf
the attacker and destroy it with toxin-producing enzymes.
Chlamydiae fight back, says Azenabor, His work shows that, as they are
ingested, these two species of Chlamydia can manipulate the functions
of protective cells like macrophages in creative ways.
Cholesterol connection
One of the keys lies in the macrophages' cell walls, which store
cholesterol and usually tightly control it.
But when it's infected with C. pneumoniae, the microbe traffics
cholesterol from the macrophage cell membrane to its own, causing a
change in the macrophage that makes it rigid and unable to move.
The bacterium also disturbs the macrophage's production of toxins in a
process that transforms them into "signaling molecules," which support
functions that keep the bacterium alive.
"C. pneumoniae really wants to hijack the cell functions for its own
use, like a parasite would," he says. "The macrophage, though, wants
to kill Chlamydia, but its killing ability has been converted to
signaling."
This is the reason the infection becomes chronic, Azenabor says.
"Because of signaling, everything else in the human cell is still fine
except for the altered toxins, so the bacteria can reproduce in a
short time."
As the macrophages become immobile, they accumulate in the blood
vessel walls, setting the stage for atherosclerosis. <sniP>
-----------------------------------------------
Would be an interesting trial...But will killing the chlamydia clear
the
plaques?
Who can we find?
How about Cruiser?
I'd expect the same for this as with shegoi (creosote).
Maybe 6-10% clearings at most then plateau?
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randall... patch those links, methinks.