Mostly ABOUT Glutathione & Psor
randall
What kind of bug is it for psoriasis?
Will NAC knock it down? Or will it only slow the flare?
If it is a gut bug then we may be able to slay the PSOR beast and
drink from the GRAIL of CLEAR once again.
www.ncbi.nlm.nih.gov/pubmed/19901061
Precarious balance: Th17 cells in host defense.
Peck A, Mellins ED.
Department of Pediatrics, Division of Immunology and Transplantation
Biology, Stanford University School of Medicine, Stanford, California
94305, USA.
Lineage-specific responses from the effector T cell repertoire form a
critical component of adaptive immunity. The recent identification of
Th17 cells-a third, distinct lineage of helper T cells-collapses the
long-accepted paradigm in which Th1 and Th2 cells distinctly mediate
cellular and humoral immunity, respectively. In this minireview, we
discuss the involvement of the Th17 lineage during infection by
extracellular bacteria, intracellular bacteria and fungi. Emerging
trends suggest that the Th17 population bridges innate and adaptive
immunity to produce a robust antimicrobial, inflammatory response.
However, because Th17 cells mediate both host defense and pathological
inflammation, elucidating mechanisms that attenuate but do not
completely abolish the Th17 response may have powerful implications
for therapy.
PMID: 19901061
So we either lower Th17 or raise IL-10. Then we clear up.
And if we use immunosuppressants we risk increased infectious events.
www.ncbi.nlm.nih.gov/pubmed/19900268
Why risk PML --> brain cancer for a skin malfunction?
So why not hope it's a bug in the pathway that can be controlled?
That way we have the best of all possible worlds.
We knock down a gut bug and simply clear up.
Surely the supplement turbo chargers can help out but
wouldn't you rather tune the engine you've got without
turboing that puPPy out?
Unless you fear the flu then by all means use the Howard
Friel formula: selenium, vitamin E, NAC/
glutathione, resveratrol, and quercetin
This post from moi puts some of my ideas in to perspective:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_thread/thread/39e1ca389600fd40/fa0d89a08a671951?hl=en&q=galectin-9+psoriasis
But WHAT is it in the GUT exactly? A bug, commensal flora or
genetics?
We need to know and to do that we have to eliminate the possible
culprits, like SFB for one.
Until i eliminate SFB (segmented filamentous bacterium) it's the buggy
target.
www.ncbi.nlm.nih.gov/pubmed/19897957
The genetic basis of inflammatory bowel disease.
Cooney R, Jewell D.
Nuffield Department of Medicine, Oxford University, Oxford, UK.
Twin studies and large-scale population studies have confirmed an
increased sibling risk for both Crohn's disease (CD) and ulcerative
colitis (UC). Unlike single gene disorders, CD and UC are thought to
result from a complex interplay of multiple genes and environmental
factors. The confirmation of CARD15/NOD2 as a CD susceptibility gene
in the late 1990s caused much excitement in the field of complex
diseases in general and since then, the rapid rate of progress in
molecular genetics, with the advent of large-scale affordable
genotyping techniques, has resulted in large collaborations and the
identification of over 30 inflammatory bowel disease (IBD)-associated
genes. In particular, the importance of the innate immune system has
been reaffirmed with the identification of IRGM and ATG16L1 genes in
the autophagy pathway as CD susceptibility genes. Disturbance in the
adaptive immune system, in particular the IL-23/Th17 axis, has also
shown to be of importance for IBD overall. In this era of genome-wide
association studies it may be possible to, at last, identify the
multiple genes involved in IBD and thus improve our understanding of
the genotype-phenotype correlation and improve treatment.
PMID: 19897957
So, if Th17 is being inducted by SFB in the intestinal tract (Gi
tract-- ileum)
www.ncbi.nlm.nih.gov/pubmed/19836068
Then we need to know that.
SFB, segmented filamentous bacteria could be the answer for a host of
people with elevated th17 cells.
Did you know that I recently found L. plantarum, which kills SFB, to
be in horse feed?
We can now prevent Th17 problems better in horses then US. LOL
But i've gotten the word out at least. :)
http://groups.google.com/groups/search?hl=en&q=l.+plantarum+randall+psoriasis&sitesearch=
And i even told JRStern to eat L. plantarum on FEB 26, 2007
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/134733dbdedebdb3
Oh geez, it said to take Lactobacillus reuteri and Lactobacillus casei
but not L. Plantarum,
so gosh, i'm saying it now. LOL
AS killing SFB with L. plantarum isn't just horse feed.
OH WAIT. It is horse feed and it's patented.
http://www.allaboutfeed.net/news/new-company-launched-mlr-innovations-3735.html
[...]
MLR Innovations focuses its energies on probiotics, silage inoculants,
gel products, novel nutritional additives and other inventive
technologies for the livestock, companion animal and crop preservation
industries. The company manufactures primarily private label products.
MLR has licensed the patented Lactobacillus plantarum (Jl:l) bacterial
culture and Fermented Oat Based Feeding Technology from
[...]
In addition, MLR is closely collaborating with PROJ-X, Inc. MLR and
PROJ-X have jointly developed an equine product called E-H2O 500/200.
This technology allows vitamin E to be readily absorbed into the blood
3 times higher and faster than traditional forms of Vitamin E.
<sniP>
Good gut flora and easily absorbed vitamin E for your pony.
When will you treat your self to finish first in your breeder cuP?
Life is a derby, so finish FIRST and not an also RAN.
====================
And bingo was his NAME
Bicarbonate-Mediated Stimulation of RegA, the Global Virulence
Regulator from Citrobacter rodentium.
Yang J, Dogovski C, Hocking D, Tauschek M, Perugini M, Robins-Browne
RM.
Department of Microbiology and Immunology, Bio21 Molecular Science and
Biotechnology Institute, The University of Melbourne, Victoria 3010,
Australia; Murdoch Childrens Research Institute, Royal Children's
Hospital, Parkville, Victoria 3052, Australia.
The global virulence regulatory protein RegA, an AraC-like regulator,
controls the expression of more than 60 genes in the mouse enteric
pathogen Citrobacter rodentium. In the presence of bicarbonate, RegA
activates the transcription of a number of virulence determinants and
inhibits the expression of a series of housekeeping genes. To
elucidate the molecular mechanism by which bicarbonate stimulates RegA
activity, we carried out biophysical and mutational analyses. Our data
indicate that RegA exists as a dimer in solution regardless of
bicarbonate concentration. A leucine zipper, located in the region
downstream of the N-terminal domain, is responsible for dimerisation.
The N-terminal arm itself is involved in modulating the response to
bicarbonate, which appears to bind to a region comprising a series of
beta-sheets within the N-terminal domain. The presence of bicarbonate
relieves the autoinhibition of RegA activity by its N-terminal arm.
RegA is the first example of a bacterial virulence regulator that
utilises the light switch mechanism, previously described for the
Escherichia coli AraC protein, to respond to a gut-associated effector
that controls its activity.
PMID: 19853617
Wow ... ok... i should have already known this. <w>
==========
http://www.designtaxi.com/news.php?id=29443&page=1
[...]
DraftFCB Healthcare New York received the Grand Global Award for
Communication to the Healthcare Professional for “Live in My Skin
Video Campaign” for client Centocor. In an effort to persuade
dermatologists to empathize with the burden that psoriasis patients’
face, DraftFCB Healthcare utilized Hollywood make-up artists to
transform three dermatologists into psoriasis patients. The agency
chronicled the social experiment which allowed dermatologist to see
beyond the skin lesions and to experience the psychological aspect of
the disease themselves. The program aired on Physicians Television
Network (PTVN) and targeted the doctors with direct content at their
home while they were watching television. The video campaign resulted
in an incredible 90% of dermatologists polled gaining the
psychological understanding of the disease after viewing this 30
minute video program.
<sniP>
-----------
Get rid of hiv and prostate cancer at the same time
http://news.biocompare.com/News/NewsStory/297948/NewsStory.html
keywords:
The molecules — called “antibody-recruiting molecule targeting
HIV” (ARM-H) and “antibody-recruiting molecule targeting prostate
cancer” (ARM-P) — work by binding
<sniP>
==========
What a really super suPPlemental cocktail to cure heart disease?
Right on...
http://www.internetwks.com/owen/HeartCureRD.htm
The Cure for Heart Disease: Condensed
By Owen R. Fonorow, Copyright 2004
[...]
Heart disease orthomolecular protocol
NOV 2005: UPDATED PROTOCOL HERE
Take Vitamin C as ascorbic acid (or sodium ascorbate, but this form
may be less effective) up to bowel tolerance (3 to 18 g per day in
divided doses.)
The half-life of vitamin C in the blood stream is 30 minutes. NIH
findings indicate minimum 500 mg every 4 hours leads to highest
sustained blood levels, take more before bed, trips, etc. Trouble with
bloating/gas/diarrhea after your vitamin C? Try Liposomal Vitamin C
Take Lysine. 2 to 3 g daily for prevention and from 3 to 6 g daily for
the greatest therapeutic benefit.
Supplement Coenzyme Q10 (100 - 300 mg) (Note: Vitamin C and several
vitamins will help stimulate your own synthesis of CoQ10. CoQ10 is a
vital substance for energy and proper heart function. Popular drugs
interfere with your body's own production of CoQ10, and they may lead
to heart failure)
Take Proline from 250 mg to 2000 mg daily. (This added factor may
lower elevated Lp(a) within 6 to 14 months.)
NEW: Eliminate man-made/processed fats, such as trans and hydrogenated
fats, and supplement Omega-3 rich oils. "Research has shown that an
Omega-3 Index of 8 percent to 10 percent reduces a person's relative
risk of death from coronary heart disease by 40 percent, and from
sudden cardiac death by 90 percent." This benefit probably results
from restored insulin-mediated glucose/vitamin C uptake into cells.
[See: Protocol for Reversing Diabetes Type II by Eliminating
Hydrogenated and Trans Fats and adding Omega-3 oils... ]
Note: Following an Atkins-style diet will eliminate most trans fats
because these "poisons" appear mostly in processed carbohydrate foods
such as cookies, crackers, snacks, etc. Butter is vastly supperior to
margarine. Natural saturated fats are vastly superior to any fats or
oils processed for longer shelf life.
NEW: Eliminate ordinary sugar and refined carbohydrates. New research
confirms Dr. John Ely's 30-year theory that sugar (glucose) competes
with ascorbic acid (Vitamin C) for insulin-mediated uptake into cells.
Taking sugar can effectively crowd out the Ascorbate. The effect of
the Pauling Therapy is reportedly much more pronounced and immediate
when sugar is eliminated (and good Omega-3 fatty acids are added.)
Follow Paulings general heart and cardiovascular recommendations
provided in his book HOW TO LIVE LONGER AND FEEL BETTER , e.g.,
Vitamin E - 800 to 3200 iu ,Vitamin A - 20,000 to 40,000 iu , andSuper
B-Complex, esp. Vitamins B6 and B3
Supplement the mineral Magnesium (300 to 1500 mg) and avoid Manganese
(No more than 2 mg. USDA researchers report that elevated manganese,
more than 20 mg daily, competes with magnesium uptake in the heart
causing irregular heart beats.)
Manganese alters mitochodrial integrity in the hearts of swine
marginally deficient in magnesium ... These results suggest that high
Mn, when fed in combination with low Mg, disrupts mitochondrial
ultrastructure and is associated with the sudden deaths previously
reported.
Eat salt, only unrefined salt, Brownstein discovered literature that a
low-salt diet can cause the body to change its hormonal balance as it
attempts to retain sodium. This leads to a 400% chance of heart attack
in those with high blood pressure and low sodium intake [*]. Refined
(ordinary table salt) is poisonous, but unrefined salt has over 80
minerals and can be considered a necessary "health food."
Avoid supplemental calcium, and supplement vitamin K for proper
calcium metabolism, especially if you have taken antibiotics or blood
thinners in the past.
Add a good mineral/multivitamin
Supplement the amino acids Taurine, Arginine and Carnitine (1 to 3
g).
<sniP>
This is the condensed condensed version, go to the link for the whole
thing.
And for further reading on this heart felt topic:
http://www.vitamincfoundation.org/page2.shtml
and
http://www.healthsalon.org/456/lysine-proline-and-vitamin-c-for-arteriosclerosis/
Mentions: Vitamin K2(Menaquinone-7), folic acid, vitamin B12, vitamin
B6, and trimethylglycine
==============
If this is true. How many people would be alive right now
and how much money the health care system would miss out on?
Zillions but those supplement folks will be in nirvana.
We could go back to EDEN.
But our GOV folks would make a law against it. LOL
The tax for living in EDEN is half of your GROSS wealth.
Would you pay?
And stay or not? And for go the conversation with the ONE on high?
================================
Durk Pearson and Sandy Shaw--- FLU protection:
http://www.life-enhancement.com/article_template.asp?ID=2112
[...]
The evidence led us to a protective combination that consists of the
flavonoid quercetin, green tea extract, resveratrol, N-acetylcysteine,
vitamin D, and vitamin C. These ingredients have been reported to have
significant anti-viral effects in cell culture and animal studies, and
in a few human clinical trials.
[...]
Resveratrol
A recent paper1 reported beneficial effects against the influenza A
virus in both cell culture and in influenza-virus infected mice. The
resveratrol treated influenza-infected mice had significantly improved
survival and decreased pulmonary viral titers (98% lower) as compared
to the non-treated influenza-infected mice. The data indicated that
resveratrol’s antiviral activity in cell culture was “largely related
to its inhibition of virus life-cycle steps that occur 1–9 hours after
infection . . .” No significant inhibition of viral replication
occurred when resveratrol was added to culture 9 hours after
infection. The authors’ study of possible mechanisms of resveratrol’s
antiviral effects in cell culture led them to conclude that “[o]ur
data strongly suggest that RV’s [resveratrol’s] antiviral effects are
related to the inhibition of PKC [protein kinase C, an intracellular
signaling molecule] activity and its dependent pathways.” In other
words, resveratrol interfered with infection by altering cellular
pathways, rather than acting directly against the virus itself.
The mice were inoculated with virus and, one hour later, given i.v.
resveratrol at a dosage of 1 mg/kg/day or placebo, with treatments
repeated daily for the next 7 days. Only 20% of the infected mice
treated with placebo were alive by 10 days after infection, whereas
40% of the resveratrol-treated infected mice survived to day 10. As
the authors explained, “[n]one of the mice that survived to day 10
after infection showed any signs of disease for the next 3 months and
were considered to be cured.”
<sniP>
Enough said?
KNOCKing down PKC with resveratrol Makes sense and CLEAR skin in the
game of being clearer.
I use www.longevinex.com
How many hits for PKC + kinase in our group?
Try 96 returns for keywords: PKC + kinase
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=PKC+kinase
124 hits for PKC in p ng:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=PKC+&qt_g=Search+this+group
The second hit after the first one by Manfred points up LOW Dose
Naltrexone
to tighten junctions in the gut and block the zonulin protein that
makes them LOOSE.
search: zonulin + PKC 3 hits in the p ng:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=PKC+zonulin
----------
What about zinc for the flu?
Determine your zinc needs for less then $15 with zincmate:
http://www.vrp.com/ProductPage.aspx?ProdID=7545&zType=1
-----------
Mercola Funny flu virus vaccine thing:
http://articles.mercola.com/sites/articles/archive/2009/11/10/Hilarious-Swine-Flu-Video.aspx
Mercola: Take vitamin D and exercise to avoid the flu
http://articles.mercola.com/sites/articles/archive/2009/11/10/Canadian-Provinces-Suspend-Seasonal-Flu-Shots-and-Recommend-Vitamin-D.aspx
Mercola good gut bacteria and eating right:
http://articles.mercola.com/sites/articles/archive/2009/11/10/Dietitian-Says-Eating-Right-Is-Best-Way-to-Optimize-Good-Gut-Bacteria.aspx
Don't eat sugar and make these fermented foods yourself:
•Natto Miso Kimchee Tempeh Kefir Yogurt Olives Sauerkraut Pickles
Sally Fallon cookbook to obtain Optimal wellness: Nourishing
Traditions
http://www.amazon.com/exec/obidos/ASIN/0967089735/optimalwellnessc
============================
And just important is Glutathione?
It's huge and since it's now tomorrow for me,
i'm posting this. LOL
http://www.vrp.com/articles.aspx?ProdID=2789
Liposomal Glutathione
Crucial to Health and Longevity
By Tim Guilford, MD
Glutathione is known to be a critical component of both the
antioxidant and detoxification systems.
Glutathione is a tripeptide, a naturally occurring protein that is
composed of three amino acids: glycine, glutamine and cysteine. It is
made by every cell in the human body and it plays a part in the
function of every cell in the body. Glutathione also contains a sulfur
molecule. Sulfur plays a major role in glutathione’s antioxidant and
detoxification functions, and it also gives glutathione its
distinctive sulfurous aroma.
Powerful Antioxidant
While vitamin C and vitamin E are better known, the ability of
glutathione to work with enzymes makes it the more reliable
antioxidant workhorse for the human antioxidant system. When nutrients
are discussed, the topic of oxidative stress frequently comes up.
Oxidative stress refers to the changes that occur in the biochemistry
of molecules in the body when they interact with oxygen. In the
outside world oxidative stress shows up as rust. Inside the body,
oxidative stress is harder to visualize, but it causes damage to cells
and the membranes of cells.
Without adequate glutathione function, oxygen metabolism in the energy
producing sites in the cell called mitochondria can form an increased
number of free radicals. Free radicals are electron “hungry” and will
pull electrons from surrounding structures such as proteins or
membranes, causing them to stop functioning normally. When this
happens it is called “free radical damage,” which will cause a
decrease in the function of the cell. Free radicals must be
neutralized or this “rust” will cause cells to perform poorly or die.
Accumulation of damage to cells leads to problems in entire organs and
eventually disease. Illnesses such as the Chronic Fatigue Syndrome may
be related to decreased energy production from individual cells.11
Glutathione is one of the major defenders against oxidative stress. In
its “reduced” (active) form it can donate an electron and behave as an
antioxidant. After losing an electron, it becomes non-functional, or
“oxidized.” The ratio of reduced to oxidized glutathione in cells is a
measure of oxidative stress. Studies have shown that oxidative stress
increases with aging and it is no wonder that over time free radicals
can lead to degenerative diseases: heart disease, memory problems,
cancer, diabetes, arthritis.
The discovery and path of understanding of glutathione began in 1888,
culminating in 1926 when its structure was finally determined.1-2
Glutathione is so important to the utilization of oxygen in our bodies
that is difficult to write about oxidative stress without mentioning
it, so glutathione shows up often in the scientific literature. In
1999 a single-word search on glutathione pointed out that 40,000
articles were found in the government library under the search term
“glutathione.”3 In the past ten years, this number has more than
doubled and is now over 87,000 references. The numbers of research
articles show that research into the role that glutathione plays in
maintaining cell function is ongoing and important.
In certain disease conditions, glutathione does not get manufactured
as efficiently as needed. The lack of glutathione can result in
disease conditions from a systemic decrease as we see in
atherosclerosis. Glutathione can also be deficient in local tissues as
has been shown with asthma.4 In situations where there is a lot of
oxidative stress, as occurs in diabetes that is not well controlled,
glutathione is not formed and becomes deficient even when the building
block amino acids such as cysteine are abundantly available.5
The Great Detoxifier
Glutathione is also known as a detoxifying agent. Most toxins are able
to pass through fatty membranes, so they tend to accumulate inside of
cells. Binding toxins with glutathione makes the combination water
soluble and allows its removal.
The liver harbors the most concentrated source of glutathione because
it is the organ of detoxification. Your body uses glutathione to
protect you from pollution, radiation, drugs, carcinogenic chemicals
and heavy metals. Modern living even exposes us to toxins in our water
and food. Dealing with this onslaught is especially difficult for
people with certain neurological conditions such as autism, because
they have difficulty ridding their bodies of toxins.
Glutathione has the ability to bind with toxins directly, especially
if the correct type of matchmaker enzyme is present. About 10-30
percent of the population will not have this enzyme that enhances
glutathione function,7 and in these cases increasing the presence of
glutathione may help increase the chance of a GSH molecule matching up
with a toxin.
Toxins such as mercury are removed from the body by direct conjugation
with glutathione.8
Glutathione can attach to metals and other toxins directly and there
is an extensive list of biochemicals that can be bound to glutathione.
9 Once bound to glutathione, toxins become water soluble and can be
transported out of the cell and out through the liver for excretion.
Maintaining normal bowel flora and a high-fiber diet is important
during detoxification to prevent the reabsorption of toxins like
methyl mercury from the bowel.10 Other toxins, such as those produced
from molds or fungus called mycotoxins have also been shown to cause
an increase in oxidative stress and will also deplete glutathione.
With all the roles that glutathione plays, it is easy to see why there
are so many articles written about glutathione in the medical science
literature.
Glutathione and Disease
We have already mentioned several health conditions in which
glutathione plays a role. In addition, studies have shown that
alcoholics have low glutathione and so do people with Alzheimer’s
disease. Cigarette smoking depletes glutathione, and children with
autism are predisposed to low glutathione so they cannot detoxify
normally. Glutathione is suggested as a promising treatment to combat
the oxidative stress found in HIV-infected people. Long-lived women
have high levels of glutathione, and people with Parkinson’s disease
often benefit from treatment with glutathione. It also is posited that
the oxidative stress that depletes cells of glutathione increases
vulnerability to influenza.
Because heart muscle requires a lot of energy for its continual
function, it has the largest number of mitochondria per cell of any
tissue in the body. It would be logical to expect that glutathione is
also needed in the heart muscle cells to maintain function. It turns
out that studies have shown that a deficiency of glutathione is
correlated with the recurrence of heart problems after heart attacks.
12 It has also been shown that low glutathione is associated with the
progression of coronary artery disease even in healthy adults.13
Liposomal Glutathione
Recent developments with a liposomal form of glutathione suggest that
wrapping glutathione in a tiny lipid bubble called a liposome is an
excellent way to keep glutathione stable and make it available for use
in cells.6 A liposome is an extremely small (1/2 the width of a human
hair) bubble, which is also called a vesicle. Liposomes have a fat-
soluble exterior and an interior that is watery. This watery interior
can combine with water soluble materials such as glutathione.
Liposomes are made from the same type of material as our cell
membranes, phospholipids. Because they are made of the same type of
material as our cell membranes, liposomes penetrate mucosal tissues
allowing for rapid release into the blood stream. Nutrients that are
not in liposomes have to pass through the stomach to reach the liver
where they are metabolized and released into the bloodstream. Some
nutrients are destroyed or compromised by stomach acids. Liposomes
avoid the digestive system by penetrating the mucosal tissue.
Laboratory testing shows that the liposome can maintain glutathione in
the biochemical “reduced” state, the state that means it is active and
can donate an electron as an antioxidant. In an animal study,
Liposomal Glutathione was able to maintain the function of glutathione
allowing the scavenger cells to metabolize cholesterol and slow the
deposition and progression of plaque in the arteries.14 Further
studies will be needed before a definitive statement about the role
that glutathione plays in maintaining normal function in the cells
lining arteries can be made.
<sniP references>
So do you want to eat some NAC now?
Even pharma is getting on board with glutathione coated liposomes
http://www.genengnews.com/news/bnitem.aspx?name=67331403
[...]
G-Technology has been developed to transport different classes of
drugs directly across this barrier using glutathione-coated liposomes.
The company’s research partnership with Genzyme follows on from a
similar agreement with MedImmune, signed in September.
Liposomal formulation allows the encapsulation of a wide range of
compounds and biological molecules without changing their function and
protecting them against degradation and immune responses, according to
to-BBB. Coating liposomes with PEG further ensures a prolonged
circulation time in plasma. Conjugation of glutathione to the tips of
the PEG molecules targets the liposomes toward the active glutathione
transporters on the blood-brain barrier, the firm explains.
<sniP>
==================================
www.ncbi.nlm.nih.gov/pubmed/19877036
Association of ERAP1, but not IL23R, with ankylosing spondylitis in a
Han Chinese population.
Davidson SI, Wu X, Liu Y, Wei M, Danoy PA, Thomas G, Cai Q, Sun L,
Duncan E, Wang N, Yu Q, Xu A, Fu Y, Brown MA, Xu H.
Princess Alexandra Hospital, University of Queensland, Brisbane,
Queensland, Australia.
OBJECTIVE: The results of a recent genome-wide association study have
shown that ERAP1 and IL23R are associated with ankylosing spondylitis
(AS) in Caucasian populations from North America and the UK. Based on
these findings, we undertook the current study to investigate whether
single-nucleotide polymorphisms (SNPs) covering the genes ERAP1 and
IL23R are associated with AS in a Han Chinese population. METHODS: A
case-control study was performed in Han Chinese patients with AS (n =
527) and controls (n = 945) from Shanghai and Nanjing. All patients
met the modified New York criteria for AS. The Sequenom iPlex platform
was used to genotype cases and controls for 21 tag SNPs covering IL23R
and 38 tag SNPs covering ERAP1. Statistical analysis was performed
using the Cochran-Armitage test for trend. RESULTS: Multiple SNPs in
ERAP1 were significantly associated with AS (for rs27980, P = 0.0048;
for rs7711564, P = 0.0081). However, no association was observed
between IL23R and AS (for all SNPs, P > 0.1). The nonsynonymous SNP in
IL23R, rs11209026, widely thought to be the primary AS-associated SNP
in IL23R in Europeans, was found not to be polymorphic in Chinese.
CONCLUSION: Our results demonstrate that genetic polymorphisms in
ERAP1 are associated with AS in Han Chinese, suggesting a common
pathogenic mechanism for the disease in Chinese and Caucasian
populations, and that IL23R is not associated with AS in Chinese,
indicating a difference in the mechanism of disease pathogenesis
between Chinese and Caucasian populations. This may result from the
fact that rs11209026, the nonsynonymous SNP in IL23R, is not
polymorphic in Chinese patients, providing further evidence that
rs11209026 is the key polymorphism associated with AS (and likely
inflammatory bowel disease and psoriasis) in this gene.
PMID: 19877036
ERAP1?
OK,
http://en.wikipedia.org/wiki/ARTS-1
Symbols ARTS-1; A-LAP; ALAP; APPILS; ARTS1; ERAAP; ERAP1; KIAA0525;
PILSAP
Type 1 tumor necrosis factor receptor shedding aminopeptidase
regulator, also known as ARTS-1, is a protein which in humans is
encoded by the ARTS-1 gene.[1]
ARTS1 is also known as:
ER aminopeptidase 1 (ERAP1)
ER aminopeptidase associated with antigen processing (ERAAP)
Adipocyte-derived leucine aminopeptidase (ALAP)
Puromycin-insensitive leucine aminopeptidase (PILS-AP)
Function
ARTS-1 is a member of the M1 family of zinc metallopeptidases which
acts as a aminopeptidase that degrades oligopeptides by cleavage
starting at the amino terminus. One of the functions of
aminopeptidases is to degrade potentially toxic peptides in the
cytosol.[1]
ARTS-1 is a transmembrane protein that is localized to the endoplasmic
reticulum. It has been implicated in the following functions:
Shedding of various cytokine receptors and decoy receptors
Trimming of antigenic peptides before binding to MHC class I,
affecting antigen presentation to cytotoxic T lymphocytes
OMG, omg it says, in the ER it's localized...and is zincy.
RECALL: http://en.wikipedia.org/wiki/Endoplasmic_reticulum
And now recall LL37 or LL-37.
Then toss some LPS and TLR's in the salad.
www.ncbi.nlm.nih.gov/pubmed/18625310
TLR accessory molecules.
Akashi-Takamura S, Miyake K.
Division of Infectious Genetics, Department of Microbiology and
Immunology, The Institute of Medical Science, The University of Tokyo,
4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
Accessory molecules are required for microbial recognition by Toll-
like receptor (TLR), subsequent signaling, and regulation of ensuing
immune responses. Accessory molecules regulate TLRs on the cell
surface (MD-2 and RP105), or in the endoplasmic reticulum (ER)
(Unc93B, PRAT4A, and gp96). Other types of accessory molecules
modulate TLR responses by acting directly on TLR ligands (CD14, CD36,
HMGB1, and the antimicrobial peptide LL37). These molecules cooperate
with TLR, inducing appropriate defense mechanisms. It is important to
understand how TLR signaling is controlled by these accessory
molecules. These accessory molecules could be promising targets for
therapeutic intervention in infectious disease and immune disorders.
PMID: 18625310
=========================
How does one know he's well.
Is it a thought process?
Like, I think i'm well?
Or more WELL would be swell?
Or is true wellness, when you don't think but simply KNOW?
So, is knowingness enough?
Like for the econonmy perhaps?
Do you think or know abut the financial prospect of this country?
I thought when oBLAME-OH! said that bush spent to much and that the
war
was draining precious tax dollars he would follow through and stop
spending and curtail the war?
Why did he do the oPPosite?
=======================
Is the stimulus all Bogus?
And what about another one?
Is this FDR II or what?
And will obamaramadingdongalama be cursed to a W recession?
I sure hope not but it sure looks like it's gonna happen.
He's like a chick with a credit card and in need of a new ward robe.
Do real leaders cry about what the other guy did?
NO, they lead.
But was the stimulus suPPOse to go to topical sunshine for psor heads?
Check it out.
http://www.cleveland.com/medical/index.ssf/2009/11/stimulus_grants_mean_jobs_for.html
Stimulus grants mean jobs for local medical institutions
By Sarah Jane Tribble, The Plain Dealer
[...]
The cancer center has committed to providing additional support after
the funding has run out, in two years, to "make sure folks can
maintain those jobs," he said.
Oliver "Pudge" Henkel, chief government affairs officer for the
Cleveland Clinic, also confirmed that jobs would need to be added to
fulfill the research. If money is not available in future years
through the NIH, Henkel said the Clinic "will support that research
activity."
Many of the projects at local institutions are for "translational
research," which means clinicians can quickly translate research to
clinical practice to help patients.
Kevin Cooper, a professor and researcher of dermatology at CWRU and
chairman of the department of dermatology of UH Case Medical Center
and CWRU, said his grant funding for psoriasis research will jump-
start a project that was at risk of languishing.
Cooper's research proposes a new way to treat psoriasis, a common skin
disease that causes cells to build up on the skin's surface. The
technique called photodynamic therapy uses a combination of red light
and a drug applied to the skin.
"This is one where we had reached kind of an obstacle that actually
couldn't be gotten around without supplemental funds," Cooper said.
"So the whole development of this treatment -- this novel treatment
that could be safer -- would have come to a halt."
<end>
Oh wow stimulust for a new type of sun beam on your psor.
Why don't they just toss the money in to a gutter?
=============
Do a glutamine + psoria* search:: 10 hits
Check out citrulline
here's two::
Molecular identification and expression analysis of filaggrin-2, a
member of the S100 fused-type protein family.
Wu Z, Hansmann B, Meyer-Hoffert U, Gläser R, Schröder JM.
Department of Dermatology, University Hospital of Schleswig-Holstein,
Kiel, Germany.
Genes of the S100 fused-type protein (SFTP) family are clustered
within the epidermal differentiation complex and encode essential
components that maintain epithelial homeostasis and barrier functions.
Recent genetic studies have shown that mutations within the gene
encoding the SFTP filaggrin cause ichthyosis vulgaris and are major
predisposing factors for atopic dermatitis. As a vital component of
healthy skin, filaggrin is also a precursor of natural moisturizing
factors. Here we present the discovery of a member of this family,
designated as filaggrin-2 (FLG2) that is expressed in human skin. The
FLG2 gene encodes a histidine- and glutamine-rich protein of
approximately 248 kDa, which shares common structural features with
other SFTP members, in particular filaggrin. We found that FLG2
transcripts are present in skin, thymus, tonsils, stomach, testis and
placenta. In cultured primary keratinocytes, FLG2 mRNA expression
displayed almost the same kinetics as that of filaggrin following Ca
(2+) stimulation, suggesting an important role in molecular regulation
of epidermal terminal differentiation. We provide evidences that like
filaggrin, FLG2 is initially expressed by upper granular cells,
proteolytically processed and deposited in the stratum granulosum and
stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and
filaggrin may have overlapping and perhaps synergistic roles in the
formation of the epidermal barrier, protecting the skin from
environmental insults and the escape of moisture by offering
precursors of natural moisturizing factors.
PMID: 19384417 [PubMed - indexed for MEDLINE]
---------
Almost all about citrulline in mammals.
Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S,
Cynober L.
Laboratoire de Biomathématiques, E.A. 2498, Faculté de Pharmacie,
Université René Descartes, Paris, France. emmanuel.curis@univ-
paris5.fr
Citrulline (Cit, C6H13N3O3), which is a ubiquitous amino acid in
mammals, is strongly related to arginine. Citrulline metabolism in
mammals is divided into two fields: free citrulline and citrullinated
proteins. Free citrulline metabolism involves three key enzymes: NO
synthase (NOS) and ornithine carbamoyltransferase (OCT) which produce
citrulline, and argininosuccinate synthetase (ASS) that converts it
into argininosuccinate. The tissue distribution of these enzymes
distinguishes three "orthogonal" metabolic pathways for citrulline.
Firstly, in the liver, citrulline is locally synthesized by OCT and
metabolized by ASS for urea production. Secondly, in most of the
tissues producing NO, citrulline is recycled into arginine via ASS to
increase arginine availability for NO production. Thirdly, citrulline
is synthesized in the gut from glutamine (with OCT), released into the
blood and converted back into arginine in the kidneys (by ASS); in
this pathway, circulating citrulline is in fact a masked form of
arginine to avoid liver captation. Each of these pathways has related
pathologies and, even more interestingly, citrulline could potentially
be used to monitor or treat some of these pathologies. Citrulline has
long been administered in the treatment of inherited urea cycle
disorders, and recent studies suggest that citrulline may be used to
control the production of NO. Recently, citrulline was demonstrated as
a potentially useful marker of short bowel function in a wide range of
pathologies. 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. Protein citrullination results from post-translational
modification of arginine; that occurs mainly in keratinization-related
proteins and myelins, and insufficiencies in this citrullination occur
in some auto-immune diseases such as rheumatoid arthritis, psoriasis
or multiple sclerosis.
PMID: 16082501
======================
http://www.medicalnewstoday.com/articles/170357.php
Researchers Discover Immune Cells That Prevent Asthma In Mice
Researchers in Belgium have discovered that a type of immune cell
previously not well understood helped mice from developing an allergic
reaction to certain airborne particles that can trigger asthma: they
suggest these cells, called lung interstitial macrophages (IMs), may
have the same effect in humans.
The study was the work of Fabrice Bureau and colleagues, at the
University of Liège, Belgium, and was published online on 9 November
in the Journal of Clinical Investigation.
Our respiratory tract is continually bombarded by microbe-derived
molecules. Their arrival triggers numerous immune system responses,
and the arrival of one particular molecule, lipopolysaccharide,
commonly known as LPS, triggers asthma in some people.
However, what is not well understood is why, when everyone breathes in
LPS, doesn't everyone develop asthma?
In this new study, Bureau and colleagues believe they have discovered
an important clue, because in mice they found that lung interstitial
macrophages (IMs) prevented lung immune cells known as dendritic cells
from triggering a Th2 immune response to LPS and an experimental
harmless airborne antigen.
(A Th2 immune response is one that tackles foreign substances outside
of cells, whereas Th1 tackles problems inside cells).
The researchers said to the best of their knowledge this was the first
time an "in vivo" function has been ascribed to IMs.
They discovered that IMs, but not another type of macrophage known as
alveolar macrophages, produced high levels of IL-10 (an anti-
inflammatory cytokine) and stopped dendritic cells activated by LPS
and loaded with the experimental harmless airborne antigen from
maturing and migrating in "an IL-10 dependent manner", thus preventing
the launch of Th2 responses.
To confirm this, they showed that removing IMs from the mice caused
them to have "overt asthmatic reactions to innocuous airborne antigens
inhaled with low doses of LPS".
Bureau and colleagues concluded that IMs help prevent airborne LPS
from promoting allergy in mice and might play a similar role in
humans.
"This study has revealed a crucial role for IMs in maintaining immune
homeostasis in the respiratory tract and provides an explanation for
the paradox that although airborne LPS has the ability to promote the
induction of Th2 responses by lung DCs [dendritic cells], it does not
provoke airway allergy under normal conditions," they wrote.
The researchers suggested future research should focus on whether
asthma in humans is caused by inhibiting or disrupting IMs.
"Lung interstitial macrophages alter dendritic cell functions to
prevent airway allergy in mice."
Denis Bedoret, Hugues Wallemacq, Thomas Marichal, Christophe Desmet,
Florence Quesada Calvo, Emmanuelle Henry, Rodrigue Closset, Benjamin
Dewals, Caroline Thielen, Pascal Gustin, Laurence de Leval, Nico Van
Rooijen, Alain Le Moine, Alain Vanderplasschen, Didier Cataldo, Pierre-
Vincent Drion, Muriel Moser, Pierre Lekeux, Fabrice Bureau.
J. Clin. Invest., Published online November 9, 2009.
DOI:10.1172/JCI39717
--------
I'm not sure these guys above want me to post this?
I did use their link. So wouldn't that be enough to direct folks to
them?
I expect so.
But they really don't explain what's what.
Only some confusing language. I do like their info.
But why can't i show it to YOU?
OK, if they don't want me to do that, then i'll use other links.
Try this:
http://www.physorg.com/news177059033.html
Interstitial macrophages: immune cells that prevent asthma
November 10, 2009 The continual presence in the air of the microbe-
derived molecule LPS promotes asthma in some individuals. What
prevents inhalation of LPS from promoting asthma in most individuals
is not well understood. However, researchers have now ascribed this
function in mice to a population of lung immune cells known as lung
interstitial macrophages (IMs); this is the first in vivo function
described for these cells.
Microbe-derived molecules able to stimulate the immune system are
omnipresent in the air, and the presence of one such molecule (LPS)
promotes asthma in some individuals. What prevents inhalation of LPS
from promoting asthma in the majority of individuals is not well
understood. However, Fabrice Bureau and colleagues, at the University
of Ličge, Belgium, have now ascribed this function in mice to a
population of lung immune cells known as lung interstitial macrophages
(IMs). Surprisingly, this is the first in vivo function described for
these cells.
The way in which airborne LPS promotes asthma is by inducing lung
immune cells known as DCs to initiate Th2 immune responses towards
normally innocuous allergens. In the study, mouse IMs were found to
produce high levels of the soluble immune factor IL-10, to inhibit LPS-
induced DC activation in an IL-10-dependent manner, and to prevent the
induction of Th2 responses directed towards innocuous allergens
following exposure to LPS and the allergen.
Importantly, mice in which IMs had been depleted developed severe
asthmatic reactions to innocuous airborne allergens inhaled with low
doses of LPS. The authors therefore conclude that IMs help prevent
airborne LPS from promoting allergy in mice and suggest that they
might have a similar function in humans; determining whether
inhibition or dysfunction of IMs contributes to the development of
asthma in humans is likely to be an area of future investigation.
More information: Lung interstitial macrophages alter dendritic cell
functions to prevent airway allergy in mice, Journal of Clinical
Investigation, http://www.jci.org/articles/view/39717?key=ilz1n88N1gsZL8Ogbs3d
Source: Journal of Clinical Investigation
==================
Broken IL-10 genes make for IBD. Is this a factor for psoriasis?
While psoriatics have low IL-10 levels, that could be explained by SFB
in the ileum. (SFB- segmented filamentous bacterium)
http://content.nejm.org/cgi/content/full/NEJMe0909225
Interleukin-10 in Inflammatory Bowel Disease
Brian Kelsall, M.D.
In this issue of the Journal, Glocker et al.1 provide the first
substantial support for a functional role for the immunosuppressive
cytokine interleukin-10 in the pathogenesis of inflammatory bowel
disease in humans. By performing genetic-linkage and candidate-gene
analysis of two unrelated consanguineous families with children who
have a severe, progressive, poorly treatable form of Crohn's disease
that occurs in the first year of life, the investigators identified
homozygous, recessive loss-of-function mutations in the interleukin-10
receptor genes, IL10RA and IL10RB, which most likely contributed to
the patients' disease. A third distinct mutation in IL10RA was found
in an unrelated patient. Finally, they report the successful treatment
of one of the patients with allogeneic hematopoietic stem-cell
transplantation, which identified hematopoietic cells as the primary
targets of interleukin-10 action in this disease.
<sniP>
=================
http://www.medicalnewstoday.com/articles/169574.php
keywords: Akt -- p55-- MPPI -- PIP3 -
-----
http://www.medicalnewstoday.com/articles/169632.php
700,000 people around the world suffer from leprosy caused by
Mycobacterium leprae.
----
Stealth bacteria -- Pseudomonas aeruginosa -- biofilm - rhamnolipids
http://www.medicalnewstoday.com/articles/169581.php
For rhamnolipid see 6th paragraph:
http://en.wikipedia.org/wiki/Polysaccharide#Bacterial_capsular_polysaccharides
-------------
randall
Bulgarian proverb--- "you are permitted in time of great danger to
walk with the devil until you have crossed the bridge."