Colitis & Ileitis Induction assoc with MARK increases in TLR 2, 4, 5
jay
SyndromeX, or if you're unlucky, intestinal damage which then can be
difficult to recover from, esp if one is already genetically
susceptible. Fructose and starch both preferentially increase E Coli
(strong TLR4 agonist). Grain-fed cows have 300x E coli vs grass-fed.
Wheat's gliadin increasing gut permeability via zonulin. And a high-
fat diet increases translocation of LPS from gut into plasma raising
system-wide inflammation, esp in adipose. Our taste buds and racks of
processed foods have conspired to do us in! When is the govmint gonna
paint skull and cross bones in the cereal and soft drink isles,
instead of banning potato purchases on WIC :)
The induction of colitis and ileitis in mice is associated with marked
increases in intestinal concentrations of stimulants of TLRs 2, 4, and
5.
BACKGROUND: Inflammatory bowel diseases (IBDs) appear to be modulated
by the interaction of pathogen-associated molecular patterns (PAMPs)
derived from intestinal bacteria with their respective innate immune
receptors, including Toll-like receptors (TLRs). We aimed to establish
if intestinal concentrations of proinflammatory bacterial ligands of
TLR2, TLR4, or TLR5 may be altered in murine IBD models, and to
characterize which of the major bacterial groups may contribute to
each signal.
METHODOLOGY/PRINCIPAL FINDINGS: PAMPs specific for TLR2 (lipopeptide
equivalents), TLR4 (lipopolysaccharide equivalents), and TLR5
(flagellin equivalents) in human and murine fecal and intestinal
samples were quantified using HEK-293 cells transfected with
respective TLRs and calibrated with defined standard PAMPs. The
induction of colitis in mice by dextran-sodium-sulphate treatment
significantly increased colonic lipopeptide (fourfold) and LPS
equivalent (550-fold) concentrations, while flagellin equivalent
concentrations remained similar. The induction of ileitis by oral
infection with Toxoplasma gondii dramatically increased ileal
concentrations of lipopeptide (370-fold), LPS (3,300-fold), and
flagellin equivalents (38-fold), all P<0.01. Analysis of
representative strains of the major bacterial groups of the human
intestine revealed that enterobacterial species are likely to be more
significant contributors of soluble TLR2 and TLR4 stimulants to the
intestinal milieu than Bacteroides species or Gram-positive
Firmicutes.
CONCLUSIONS/SIGNIFICANCE: We conclude that the induction of colitis or
ileitis in mice is associated with significant disease-specific
alterations to the PAMP profile of the gut microbiota.
Gail Michael
Gail
"jay" <jaym...@hotmail.com> wrote in message
news:58c56025-99ad-479d...@j18g2000yqd.googlegroups.com...
jay
> significant contributors of soluble TLR2 and TLR4
Below abstract relates NOD2 variant with TLR2 pathway.
NOD2 mediates anti-inflammatory signals induced by TLR2 ligands:
implications for Crohn's Disease.
Mutations of the NOD2 gene have been associated with an increased
susceptibility to Crohn's disease, but the pathogenetic mechanisms
mediated by NOD2 remain elusive. In the present study, we demonstrate
that the 3020insC frameshift-mutation in the NOD2 gene associated with
Crohn's disease results in defective release of IL-10 from blood
mononuclear cells after stimulation with the Toll-like receptor (TLR)2
ligands, peptidoglycan and Pam3Cys-KKKK, but not with bacterial LPS, a
TLR4 ligand. The potential pathophysiological significance of this
finding in patients with Crohn's disease and who are homozygous for
this NOD2 mutation was substantiated by the finding of decreased anti-
inflammatory cytokine release when cells from these patients were
stimulated with different species of Bacteroides, an enteric
microorganism implicated in the pathogenesis of Crohn's disease. In
conclusion, defective NOD2 function results in a pro-inflammatory
cytokine bias after stimulation of mononuclear cells with TLR2
stimuli, and this could contribute to the overwhelming inflammation
seen in Crohn's disease. PMID: 15214053
Gail Michael
I have no scientific knowledge of crohns.
What you write may be factors discovered after crohns is discovered in the
body. The cause is a simple one. and yet complicated in a very
unreasonable way. Crohns is caused by psychiatric stimulants, Xanax,
Prozac, all anti-depressants, st johns wort, marijuana, caffeine tablets,
etc. etc. even Ritalin which is a mild stimulant. When one person ingests
any of the stimulants, there is an uncanny ability for the stress from the
stimulant to travel to a friend, relative, etc. of the ingester, no matter
the distance the person is from the ingester, and cause that person to have
crohns. Crohns is not acquired by any medical cause. It is in a class
by itself. Neither the ingester nor the victim is aware of this process.
The results are crohns, debilitating any part of the body, even depression.
What is good for the depressed person taking the anti-depressant is havoc
for innocent people. I have written this so many times, surely the drug
companies that devised the anti-depressants must be aware of this strange
process. But being their best money maker, not a word is ever forthcoming
from the drug companies. Crohns is not a side effect of the stimulants
It is a vigorous part of them. Not everybody is vulnerable. Keeping very
busy and denying the anti-depressants can cause crohns by the mind process
will keep it at bay. Thus most people deny the seemingly impossible
process causing crohns. And marijuana is also a substance that will cause
crohns in the same manner.
Hate to be so graphic, but the end result will be more illnesses occuring as
crohns will emanate more conditions and in time there will not be a safe
haven for most.
Gail
"jay" <jaym...@hotmail.com> wrote in message
news:3630c9d7-08e0-4d26...@26g2000yqv.googlegroups.com...
randall
> Maybe the "normal" modern diet promotes dysbiosis that leads to
> SyndromeX, or if you're unlucky, intestinal damage which then can be
> difficult to recover from, esp if one is already genetically
> susceptible.
You said a mouthful. What inducts the Th1 skew which leads to
Th17 then?
I do have a theory btw. LOL
> Fructose and starch both preferentially increase E Coli
> (strong TLR4 agonist). Grain-fed cows have 300x E coli vs grass-fed.
> Wheat's gliadin increasing gut permeability via zonulin. And a high-
> fat diet increases translocation of LPS from gut into plasma raising
> system-wide inflammation, esp in adipose. Our taste buds and racks of
> processed foods have conspired to do us in! When is the govmint gonna
> paint skull and cross bones in the cereal and soft drink isles,
> instead of banning potato purchases on WIC :)
You need to ask yourself what the exact trigger is and how to correct
and return to BETTER DAYs?
>
> The induction of colitis and ileitis in mice is associated with marked
> increases in intestinal concentrations of stimulants of TLRs 2, 4, and
> 5.
Yeah BUT.... their not etiological are they?
The TLR's are simply in the inflammatory pathway.
If i put you on the high or LOW path you'll meet deniZENs indigenous
to the PATH.
If you take the right mushroom and go down the rabbit hole you'll
see more mad hatter's then otherwise?
http://en.wikipedia.org/wiki/Mad_Hatter
>
> BACKGROUND: Inflammatory bowel diseases (IBDs) appear to be modulated
> by the interaction of pathogen-associated molecular patterns (PAMPs)
> derived from intestinal bacteria with their respective innate immune
> receptors, including Toll-like receptors (TLRs). We aimed to establish
> if intestinal concentrations of proinflammatory bacterial ligands of
> TLR2, TLR4, or TLR5 may be altered in murine IBD models, and to
> characterize which of the major bacterial groups may contribute to
> each signal.
OK so think NOW. There is LAB in the GAME of LIFE. lab = lactic acid
bacteria
Plus the non lab bacteria in the ~ 1,000 citters in the Gi tract.
The difference between ILL and maximum health is the RATIO of good to
BAD bacteria.
Diet simply isn't enough once the pathway's taking you down.
You have to re-create LAB and a proper milieu inside of YOU.
>
> METHODOLOGY/PRINCIPAL FINDINGS: PAMPs specific for TLR2 (lipopeptide
> equivalents), TLR4 (lipopolysaccharide equivalents), and TLR5
> (flagellin equivalents) in human and murine fecal and intestinal
> samples were quantified using HEK-293 cells transfected with
> respective TLRs and calibrated with defined standard PAMPs. The
> induction of colitis in mice by dextran-sodium-sulphate treatment
> significantly increased colonic lipopeptide (fourfold) and LPS
> equivalent (550-fold) concentrations, while flagellin equivalent
> concentrations remained similar. The induction of ileitis by oral
> infection with Toxoplasma gondii dramatically increased ileal
> concentrations of lipopeptide (370-fold), LPS (3,300-fold), and
> flagellin equivalents (38-fold), all P<0.01. Analysis of
> representative strains of the major bacterial groups of the human
> intestine revealed that enterobacterial species are likely to be more
> significant contributors of soluble TLR2 and TLR4 stimulants to the
> intestinal milieu than Bacteroides species or Gram-positive
> Firmicutes.
>
> CONCLUSIONS/SIGNIFICANCE: We conclude that the induction of colitis or
> ileitis in mice is associated with significant disease-specific
> alterations to the PAMP profile of the gut microbiota.
OK, so what do i think?
Is that what you really WANT? LOL
Shooting from the hiP?
I'll give it a TRY via googleisms. And avoid zanax till closing
thoughts?
OK...
If this is what your ileum looks like (if this is an ileum) then all i
can say is
thank GOD i've got psoriasis.
http://www.medgadget.com/archives/img/crohn.jpg
OTOH when my outside psor condition was severe i'd most likely trade
it for inside skin (Gi tract - git) in the game and
play hide the pain?
Yikes .... ouch... even the thought is painful. :(
And once again LOOKs pain filled:
http://www.medgadget.com/archives/img/crohn.jpg
Certainly crohn's is inclusive of the entire GASTRO intestinal tract?
Yet, my first impulse is:
Where does it start or originate?
http://www.fascrs.org/patients/conditions/crohns_disease/
http://cms.fascrs.org/global/images/migrated/crohns.gif
from:
A longstanding question in for those studying inflammatory bowel
syndromes:
Is Crohn's disease an autoimmune disorder?
http://www.forbes.com/lifestyle/health/feeds/hscout/2006/02/23/hscout531200.html
<randall note: i haven't read this as i'm writing this post first for
the most part>
Crohn's disease has become a prolonged enigma, the authors wrote,
although it is considered by many to be a mixture of genetic
predisposition and the effect of the body attacking its own immune
system.
But Segal set out to test another hypothesis -- that bacteria spreads
and inflames the intestines due to lowered immunity in the body - and
so he and colleagues took the unusual approach of inflicting trauma,
in the form of biopsies and skin scrapings, to Crohn's patients. He
then observed how their white blood cells responded.
Segal first took two biopsies at six hours apart from the rectums of
Crohn's patients and a control group of healthy people. He noticed
that the inflammatory response to the trauma was only a quarter of
what it should be, and that no neutrophils were present. Neutrophils
are white blood cells that provide the first line of defense against
foreign invaders in the body...
To boost this evidence of a failed immune response, and to find if the
phenomenon only occurred in the bowel region, the scientists also
sandpapered patients' skin to see how cells responded. Again, they
found very few neutrophils rushing to the trauma on the skin, even
after 24 hours. This revealed a "systemic general abnormality, not a
one-time (response)," Segal said.
In the last test, the researchers injected Crohn's patients with
killed e. coli bacteria, to find out if their bodies had abnormalities
in dealing with bacteria. In normal people, there was a florid
inflammatory response, with a tenfold increase in blood flow, but in
Crohn's patients, the blood flow was weak at best.
Fundamental stuff that might open the door to new therapies -- such as
Viagra (no joke) for boosting tissue perfusion and thus, immune access
to areas of inflammation.
More from Dr. Anthony Segal
http://www.crn.ucl.ac.uk/cgi-bin/crn_investigator_details?Menu=1&PerID=188&Org=All&OrgShortCode=UCLH&SortType=Org
But this doesn't look like his page? It's some guys to run trials on
you?
Skip it.
================
And i'll do my own thing for finding the origins of crohn's?
OK... go...
23417 crohn's hits - pubmed: <randall note: Over 30k hits for
psoriasis>
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's
Using the kicker keyword: etiology we only shave off 10,000 of those?
Amazing
13,578 hits for keywords: crohn's etiology - pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's+etiology
One can imagine that the majority of these, say THEY DON'T KNOW what
the etiology is. LOL
Thusly the keyword etiology is in SO freaking many of them.
OK and the MOST recent one has a nice clue.
YOU SCREW with THE NASCENT BIOFILM (Git) from your Mother/
breastfeeding etc and your likely chances
or severity, if it's genetical (and most likely is as family
structures attest) and
crohn's GOES uP.
So one can make it worse as you KNOW in sPades/
So what's with the gut and colon?
Easy. Make the colon slightly acidic and the problems go away?
How does one do that?
EASY.... you artificially rebreast feed the colon with the wit kit and
eat a diet
that mimics your first six months of life and reestablish LAB (lactic
acid bacteria) in
the colon.
Then your no longer EAST of EDEN so to SpEAK.
Your colon is in control of your fate mate's.
Either a garden of eating (eden for this metaphor perhaPs?) or HELL on
EARTH?
Been there... and suicide is certainly an option as i've posted a few
of those articles recently.
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=suicide&start=0&scoring=d&hl=en&
Yet sticking with it and doing what the randall tells you based on his
empirical trials behooves one.
Wit kit from AHS & David W.
http://www.thewholewhey.com/3601/162358.html
That's right. Tube is inserted in to the yin yang and good bacteria
are uPloaded.
Why? Because YOU and i know that's what you need.
A ratio of good to BAD bacteria will lower inflammation.
And northern latitude folks have a hair trigger due to their genetics.
It's a light and dark thing no doubt. <w>
http://www.ncbi.nlm.nih.gov/pubmed/20940708
Am J Gastroenterol. 2010 Oct 12.
Association Between the Use of Antibiotics in the First Year of Life
and Pediatric Inflammatory Bowel Disease.
Shaw SY, Blanchard JF, Bernstein CN.
[1] Inflammatory Bowel Disease Clinical and Research Centre,
University of Manitoba, Manitoba, Canada [2] Department of Community
Health Sciences, University of Manitoba, Manitoba, Canada.
Abstract
OBJECTIVES: The development of commensal flora in infants has been
shown to be sensitive to antibiotic use. Altered intestinal flora is
thought to contribute to the etiology of inflammatory bowel disease
(IBD), an idiopathic chronic condition. We aimed to determine if early
use of antibiotics was associated with the development of IBD in
childhood.
METHODS: Nested case-control analysis of the population-based
University of Manitoba Inflammatory Bowel Disease Epidemiologic
Database was carried out. IBD status was determined from a validated
administrative database definition. A total of 36 subjects diagnosed
between 1996 and 2008 were matched to 360 controls, on the basis of
age, sex, and geographic region. Antibiotic data were drawn from the
Manitoba Drug Program Information Network, a comprehensive population-
based database of all prescription drugs for all Manitobans dating
back to 1995. Antibiotic use in the first year of life was compared
between IBD cases and controls.
RESULTS: The mean age at IBD diagnosis was 8.4 years. Twenty-one cases
(58%) had one or more antibiotic dispensations in their first year of
life compared with 39% of controls. Crohn's disease was diagnosed in
75% of IBD cases. Those receiving one or more dispensations of
antibiotics were at 2.9 times the odds (95% confidence interval: 1.2,
7.0) of being an IBD case.
CONCLUSIONS: Subjects diagnosed with IBD in childhood are more likely
to have used antibiotics in their first year of life.Am J
Gastroenterol advance online publication, 12 October 2010; doi:10.1038/
ajg.2010.398.
PMID: 20940708
OK..... so here's all of the abstracts that should GO somewhere?
12 hits: crohn's etiology LAB - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's+etiology+LAB
Pretty Sorry i'd say. But i only looked at a few of them. Nothing is
jumPing out with this cursory
subject search. But i could and should spend a little more time.
<note: read a few more, ok?>
How come there are almost 23,500 hits for crohn's and only a handful
of ones with meat in them?
There obviously doing the rectal head insertion and not looking for
etiology.
Which i've learned is similar to psoriasis and peptic ulcers and the
h. pylori noble prize for robin marshall?
Whoops it's BARRY Marshall and robin Warren for that huge NOBEL prize.
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_thread/thread/79843b36f0920be4/4e07a39d3e6f6de5?hl=en&lnk=gst&q=marshall+nobel#4e07a39d3e6f6de5
I'm betting on Dr. Dan Littman for the nobel for SFB and autoimmunity.
Of course i deserve a mention as i found the L. Plantarum (LAB) usage
to clear segmented filamentous bacterium.
LAB rules:
http://www.ncbi.nlm.nih.gov/pubmed/19050899
Int J Colorectal Dis. 2009 Feb;24(2):231-7. Epub 2008 Dec 3.
Lactobacillus suntoryeus inhibits pro-inflammatory cytokine expression
and TLR-4-linked NF-kappaB activation in experimental colitis.
Lee JH, Lee B, Lee HS, Bae EA, Lee H, Ahn YT, Lim KS, Huh CS, Kim DH.
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee
University, 1, Hoegi, Dongdaemun-ku, Seoul, 130-701, South Korea.
Abstract
OBJECTIVE: Lactic acid bacteria (LAB) can improve disturbances of
indigenous microflora as well as inflammatory bowel diseases (IBD)
such as ulcerative colitis and Crohn's disease. We examined the
anticolitic effect of Lactobacillus suntoryeus HY7801, which inhibited
toll-like receptor (TLR)-4-linked NF-kappaB activation in human
embryonic kidney (HEK) cells, in 2,4,6-trinitrobenzenesulfonic acid
(TNBS)-induced colitic mice.
MATERIALS AND METHODS: We measured the ability of commercial and
intestinal LAB to inhibit lipopolysaccharide (LPS)-stimulated, TLR-4-
linked NF-kappaB activation in HEK cells, as well as to inhibit
colitis outcomes in TNBS-induced colitic mice. We also measured levels
of the inflammatory markers, interleukin (IL)-1beta, tumor necrosis
factor (TNF)-alpha, and IL-6, and their transcription factor, NF-
kappaB, in intestinal mucosa by enzyme-linked immunosorbent assay and
immunoblotting.
RESULTS AND DISCUSSION: LAB inhibited TLR-4-linked NF-kappaB
activation, and L. suntoryeus HY7801 was the most potent inhibitor.
Intrarectal treatment of TNBS in mice caused colon shortening and also
increased colonic expression of IL-1beta, IL-6, and TNF-alpha
expression. However, oral administration of Lactobacillus HY7801 (100
mg/kg) inhibited colon shortening (p < 0.001) and myeloperoxidase
activity in TNBS-induced colitic mice (p < 0.0002) and also decreased
colonic expression of IL - 1beta (p < 0.003), IL-6 (p < 0.0001), and
TNF-alpha (p < 0.0001). Lactobacillus HY7801 inhibited the NF-kappaB
activation and TLR-4 expression induced by TNBS, as well as the
expression of cyclooxygenase 2. Lactobacillus HY7801 also reduced the
activity of intestinal bacterial glycosaminoglycan degradation and
beta-glucuronidase induced by TNBS.
CONCLUSION: L. suntoryeus HY7801 can improve colitis via the
inhibition of TLR-4-linked NF-kappaB activation.
PMID: 19050899
OK so the LAB i use are found in kyo-dolphilus and human sourced in
Japan iirc.
Which is OK. I like them. Their LAB works FINE ive found. LOL
Eat a fish you know? Nothing fishy about that and i like their way
of thinking in general.
But LAB is LAB and the terrain is no longer in pain for you crohniac's
i'm guessing.
OK, so once you blow out the crap in your colon with LAB the small
intestine should follow suit.
If you like i can speak to David and see how many of you crohn's folks
he's helped?
Haven't spoken with him in some time so i'm due anyway?
But to my sweet whey of thinking i'd go for SFB and gut machinations
for not only psoriasis
but also crohn's and many many other autoimmunity conditions.
So?
SFB and GUT - 10 hits - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=sfb+gut
Since Dr. DAN will be in town next week (Salk Institute) i'll post his
and Ivanov's study.
#2 of the ten hits above:
http://www.ncbi.nlm.nih.gov/pubmed/20147894
Mucosal Immunol. 2010 May;3(3):209-12. Epub 2010 Feb 10.
Segmented filamentous bacteria take the stage.
Ivanov II, Littman DR.
Molecular Pathogenesis Program, New York University School of
Medicine, New York, NY, USA.
Abstract
Commensal bacteria are crucial for maturation and function of the
mucosal immune system. However, the mechanisms of these interactions
are poorly understood. In addition, the role of the composition of the
microbiota and the importance of individual species in this community
in stimulating different types of immunity are major unanswered
questions. We recently showed that the balance between two major
effector T cell populations in the intestine, IL-17(+) Th17 cells and
Foxp3(+) Tregs, requires signals from commensal bacteria and is
dependent on the composition of the intestinal microbiota. Comparison
of microbiota from Th17 cell-deficient and Th17 cell-sufficient mice
identified segmented filamentous bacteria (SFB) as capable of
specifically inducing Th17 cells in the gut. SFB represent the first
example of a commensal species that can skew the mucosal effector T
cell balance and thus affect the immune fitness of the individual.
PMID: 20147894
Since crohn's does have funky Th17 from skewed Th1's your IL-10 is LOW
and so are TREG's (foxp3) to turn off the inflammation.
The most recent link with crohn's and Th17 (via IL-23---> IL12)
http://www.medpagetoday.com/MeetingCoverage/ACG/22913
[...] Crohn's disease arises and progresses as a result of an
unregulated immune response, characterized by an excessive type 1 T
helper (Th1) T-cell response and increased cytokine production,
including tumor necrosis factor-alpha (TNF) and IL-12, Panaccione
noted in the introduction to his report.
IL-12 drives the Th1 proliferation associated with Crohn's disease,
and IL-23 stimulates Th-17 cells, leading to production of the
proinflammatory mediator IL-17. Briakinumab targets the p40 subunit
common to IL-12 and IL-23, and its safety and tolerability have been
evaluated in a phase II study, said Panaccione.
<snip>
Good LAB bacteria in the colon will raise IL-10 levels and unSKEW the
Th1-->Th17 driven inflammation.
Either believe me or NOT.
Simply do the wit kit and believe in yourself and the biofilm of LAB
bacteria you create.
It's all up to YOU one way or the other.
BUT, I think (due to dr. DAN littman)--> it's due to SFB in the ileum
which will simply down regulate due to increased LAB in the colon.
A slightly acidic COLON with high ratio's of LAB RULES...
Good luck-------> is made in this game of being BETTER and not
BITTER.
Do the implant via the wit kit and eat sweet whey for 30 days while on
a nearly baby
food diet and your LUCK might be 100% CLEAR to YOU as it is to ME.
randall
Ps - or you can go with GAILs P/V theory of modern Psychiatry being
PVism and hopped up
with THEIR drugs to FIX you. LOL
http://en.wikipedia.org/wiki/Psychiatry
http://en.wikipedia.org/wiki/Psychic_vampire
The GUT disease thusly is transmitted via evil people sucking your
life force and leaving
your biofilm exposed..
Which antibiotics must be the most evil on the planet for ALL crohn's
patients. LOL
just a thought to support GAILs empiricisms.
jay
> is the RATIO of good to BAD bacteria.
> Diet simply isn't enough once the pathway's taking you down.
> You have to re-create LAB and a proper milieu inside of YOU.
> ... artificially rebreast feed the colon with the wit kit and
> eat a diet that mimics your first six months of life
> and reestablish LAB (lactic acid bacteria) in the colon.
> A ratio of good to BAD bacteria will lower inflammation.
Is the following along your thinking?
1) LPS from gram-negative bacteria (ie E coli, Salmonella,
Enterococcus faecalis, etc) trigger TLR4 (most expressed in
epithelials (ie intestines, arteries, lung, skin)).
2) Pathways after TLR4 first activate pro-inflammatory cytokines
(TNFa, IL1b, IL6).
3) Pathways (ie P38 MAPK) also after TLR4 later activate anti-
inflammatory cytokines (primarily IL10).
We don't have enough IL10 due to genetics and/or conditions, thus the
LAB replant
Per Pubmed abstract indicate following may increase IL10. Have you
already tried all of these?
Certain probiotics.
Sun exposure.
Vitamin D3.
Exercise.
Omega 3 oils.
Garlic, curcumin, etc.
jay
> Wit kit from AHS & David W. www.thewholewhey.com/3601/162358.html
> A ratio of good to BAD bacteria will lower inflammation.
How about:
Probiotic implant (esp bifido in Kyo-D) + prebiotic (esp long-chain
FOS/GOS, ie inulin, whey?) -> Kofi's favorite butyrate -> inhibits
HDAC 11 which would otherwise prevent the following pathway at SP1:
LPS -> TLR4 -> P38 MAPK -> SP1 -> IL10.
I wish the formula for success was something easy, like E=MC2 :)
randall
> > The difference between ILL and maximum health
> > is the RATIO of good to BAD bacteria.
> > Diet simply isn't enough once the pathway's taking you down.
> > You have to re-create LAB and a proper milieu inside of YOU.
> > ... Make the colon slightly acidic and the problems go away?
> > ... artificially rebreast feed the colon with the wit kit and
> > eat a diet that mimics your first six months of life
> > and reestablish LAB (lactic acid bacteria) in the colon.
> > Wit kit from AHS & David W.www.thewholewhey.com/3601/162358.html
> > A ratio of good to BAD bacteria will lower inflammation.
>
> Is the following along your thinking?
>
> 1) LPS from gram-negative bacteria (ie E coli, Salmonella,
> Enterococcus faecalis, etc) trigger TLR4 (most expressed in
> epithelials (ie intestines, arteries, lung, skin)).
YES and recently i wondered if hiv/aids folks have leaky guts
and LPS would do what ?
They don't leak and thusly don't get a Th1 skew which would
save their lives via more TNF to eat the bad bad virals
from lowering their CD4(+)'s.
Why don't their guts leak?
I know it's a permeable thing and a virus is like
a 1,000 times smaller so it's not a problem for them,
leaky or not, their IN.
So why not make their gut leaky so they can FEND off
the evil virus with IFN and TNF?
That's what i'm thinking about in the last 24 hours.
If you want the last 30 years your outa luck. Most of it
's only a dream now. <G>
>
> 2) Pathways after TLR4 first activate pro-inflammatory cytokines
> (TNFa, IL1b, IL6).
>
> 3) Pathways (ie P38 MAPK) also after TLR4 later activate anti-
> inflammatory cytokines (primarily IL10).
>
> We don't have enough IL10 due to genetics and/or conditions, thus the
> LAB replant
>
> Per Pubmed abstract indicate following may increase IL10. Have you
> already tried all of these?
> Certain probiotics.
> Sun exposure.
> Vitamin D3.
> Exercise.
> Omega 3 oils.
> Garlic, curcumin, etc.
YES....
Garlic etc are BEST for building up glutathione.
See my last post but skip the HATE stuff meant manily for SUSAN. LOL
Don't worry i really LOVE her. Without her i'd be one man wagging his
tongue
to the four winds.
With her i can hate the spin in them?
LOL
OK, so read the very last part of my my recent post.
Mon, Oct 25 2010 12:02 pm
Subject: Goa iMAMarry randall man man TAR baby - CP-690550 =
Tasocitinib - Jak STAT & (ER)= (endoplasmic reticulum) pathWHEYs --
NAC-->Glutathione redux
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/dab1e2a5fe46700b
Let's see.
The glutathione part is about 3/4's of the way down the page to here.
[...] This next author: JJ O'Shea, i think i like?
HE's ALL jak -- STAT able?
He is?
He wrote:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692054/
The Current ____STATus____ of lymphocyte signaling: new roles for old
players (STATs in lymphocyte signaling)
[...]
I'm so HIGH on NAC right now it's a miracle i don't exPlode this very
second.
That's what she said? LOL
OK, ok, i'm OK....
But was it the seaweed pills and the sushi then?
Gosh...i sure hoPe so... i like eating them. LOL
randall... stuPid Chuck is uP tonight... but i want
mad men instead...so i'll write a thread?
OK...:)
randall
OK.... you can re-RIGHT the book or gosPel of galactose if you wish.
Or eat a FISh...
Or GOa FISH...
Or make a WISH.
But the stuff that grows the GOOD FLORA (microbiota) in your
colon is GALACTOSE.
Your body doesn't digest it so it goes right through you and
then the GOOD FLORA is FED.
One good flora bacterium can reproduce 17,000,000 times a day.
Talk about sex on steroids.
That would wear me out in less then a fraction of a second. LOL
My sweetheart would be perturbed in less time then that no doubt. LOL
<W> <G>
But that's why YOUR on a BABY FOOD diet.
Mainly CARBs and things that FEED the nascent biofilm in your colon.
Babies don't have teeth and can't chew up a cow.
Their made to suckle on mom.
Since your not going to DO THAT are YOU?
Then in order to GET a BORN AGAIN colon do what i say and eat your
SWEET WHEY.
Which breaks down to GALACTOSE.
ARE WE listening out there?
Simply GET the wit kit and do what it says.
And in 30- days you say, hey randall thank you.
randall.... your welcome....whoops that was 30 days premature?
jay
> But the stuff that grows the GOOD FLORA (microbiota) in your colon
> is GALACTOSE.
> Your body doesn't digest it so it goes right through you and
> then the GOOD FLORA is FED.
I thought that in a lactose tolerant person, lactose is split into
glucose and galactose by lactase. And the liver converts galactose to
glucose.
It seems, the following pathway
LPS > TLR4 > APC/DC > IL23 (p19 & p40) > IL23R of TH17 > IL17
and variants of L12B(encodes p40) & IL23R can produce chronic
inflammation.
If so, we need a majic herb that bind p40s or are the lactobacteria
already doing this :)
jay
Salicylanilides: selective inhibitors of interleukin-12p40 production.
Interleukin (IL)-12p40, a subunit component of both IL-12 and IL-23,
is being widely studied for its role in inflammatory disease. As part
of an effort to profile cellular signaling pathways across different
cell types, we report salicylanilide inhibitors of IL-12p40 production
in stimulated dendritic cells. Based on a hypothesis that a desirable
therapeutic profile is one that could block IL-12p40 but not IL-6
production, we engaged in directed analoging. This resulted in
salicylanilides with similar IL-12p40 related potency but enhanced
selectivity relative to IL-6 production. PMID: 18715785
Does this mean, the pot at the end of the rainbow actually holds baby
aspirin?
randall
> >> LPS -> TLR4 -> P38 MAPK -> SP1 -> IL10.
> > But the stuff that grows the GOOD FLORA (microbiota) in your colon
> > is GALACTOSE.
> > Your body doesn't digest it so it goes right through you and
> > then the GOOD FLORA is FED.
>
> I thought that in a lactose tolerant person, lactose is split into
> glucose and galactose by lactase. And the liver converts galactose to
> glucose.
OK if your problem is milk then go with beet sugar.
But what i've found is most of those folk will clear upon
the protocols in this treatment.
I figured at the time that wheat would screw with me and it
didn't. Though i did try to avoid it.
But on a baby food diet you'd be surprised how little
REAL FOOD your eating. LOL
>
> It seems, the following pathway
> LPS > TLR4 > APC/DC > IL23 (p19 & p40) > IL23R of TH17 > IL17
> and variants of L12B(encodes p40) & IL23R can produce chronic
> inflammation.
> If so, we need a majic herb that bind p40s or are the lactobacteria
> already doing this :)
It ain't an herb.
What does it is as the ratio of good flora grows. RECALL the
17,000,000 million critters from one viable LAB bacterium, then
your flora is creating IL-10.
And oddly enough simply using IL-10 systemic wide doesn't work.
Go figure, i was surprised as i thought that was ALL it would
take.
Snake some IL-10 and BINGO.
Seems that a slightly acidic milieu inside of YOU is KEY
after ALL.
But what the heck if you want to use inulin and prebiotics then fine.
Your gonna end up on the right side of the TRACKs anyway.
http://en.wikipedia.org/wiki/Inulin
http://en.wikipedia.org/wiki/Prebiotic
If this isn't enough?
Then, i see uridine now. It's in baby formula and the rna factors are
used
by hiv folks to sort of SAVE their lives? LOL
See sugarcane or
http://en.wikipedia.org/wiki/Uridine
Anyway check baby formula. Certainly that might be a tip off. LOL
http://en.wikipedia.org/wiki/Galactose#Liver_galactose_metabolism
Galactose is converted to
http://en.wikipedia.org/wiki/Glucose_6-phosphate
The next section has this:
http://en.wikipedia.org/wiki/Galactose#Metabolic_disorders
[...] Galactose-1-phosphate uridyl transferase deficiency Galactose-1-
phosphate uridyl transferase Is the most problematic, as galactose-
free diets are not effective in treating neurocognitive deficiencies
(in particular language disorders such as verbal dyspraxia)and ovarian
failure. If a galactose-free diet is administered, cataracts and acute
symptoms such as kidney and liver failure respond immediately.
Anyway one whey or the other your gonna feed GOOD flora in your colon.
And if you avoid alcohol and MEAT and whatever BABIES DON'T EAT your
in like FLINT.
You WILL GROW a few pounds of GOOD FLORA (in your colon) and It WILL
PUMP out IL-10
and TAKE down your TH1 spin (skew).
And if not then eat kimchi day and night while on the 30 day baby food
diet.
Make it yourself or buy it and let it warm up (don't refrigerate)
and then the SFB in your COLON will be decimated enough to GET WELL
again.
If that doesn't WORK, at least you TRIED.
And if you don't want to play then fine.
You can do whatever you want.
You can find the magic herb?
you said in the next post: (between the z's)
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz
I've found that aspirin will increase the leaky gut thingy.
And add to inflammation in the long run.
Even at a 62.5 mg baby aspirin dosage.
So why fight the good flora you had at birth?
Wasn't it good enough for you THEN?
Why not NOW?
Certainly northern latitude folks didn't feed their critter's
meat and alcohol from birth and didn't plan on strep or
whatever critter poked holes in the good flora biofilm?
If the good biofilm that is laid down in the first years of
life is thin'ed out and leaks don't you think it would
be BEST to restore it one whey or the other?
randall
ps - i suppose we could go to work for big pharma
and find some dirt bacterium like mtx/cyclo?
and make a zillion BUCKs... LOL :)
or JUST GET CLEAR of Ai and SFB;s?
jay
> inflammation.
Following abstracts seems to say that some NOD2 variants can increase
IL-12p40-related cytokines in monocytes. Another bridge to IL17?
NOD2/CARD15 genotype influences MDP-induced cytokine release and basal
IL-12p40 levels in primary isolated peripheral blood monocytes.
BACKGROUND: The functional link between mutations in NOD2 and Crohn's
disease (CD) has not been entirely elucidated. The 1007fs mutation
results in loss of NF-kappaB activation in response to muramyl
dipeptide (MDP) but has also been linked to an increased IL-1beta
processing and IL-12 release.
METHODS: We investigated the basal and MDP-triggered mRNA expression
and protein release for TNF-alpha, IL-10, IL-1beta, and IL-12p40 in
peripheral blood monocytes from 40 CD patients and 15 healthy
individuals with different NOD2 genotypes.
RESULTS: Monocytes from individuals with 2 mutated NOD2 alleles
(homozygous and compound-heterozygous individuals) displayed an
impaired release of TNF-alpha and IL-10 but also of IL-1beta and
IL-12p40 in response to MDP. In contrast to other NOD2 variants, the
presence of at least 1 1007fs allele in double-mutated individuals
completely abrogated NOD2 receptor function. Interestingly, monocytes
from CD patients with 2 mutated NOD2 alleles displayed significantly
higher basal levels of IL-12p40 in cell culture supernatants compared
to wildtype CD patients and control individuals (P = 0.002 and P =
0.008, respectively). This was regardless of the IL23R genotype and
was not mirrored by increased IL-12p40 plasma levels in these
individuals.
CONCLUSIONS: The CD-associated NOD2 variants lead, in a dose- and
mutation-dependent manner, to an impaired release of TNF-alpha, IL-10,
IL-1beta, and IL-12p40 in response to MDP. The finding of increased
basal levels for IL-12p40-related cytokines in monocytes with 2
mutated NOD2 alleles is likely to set a new link between NOD2
mutations and the inflammatory mechanisms underlying CD.
PMID: 18383179
randall
Jay
I know you CAN BEET this thing.
Did you get them? LOL
http://en.wikipedia.org/wiki/Galactose
sweet BEETs... <W> <G>
So how do we GET YOU SWELL AGAIN?
Don't NOD off. MAP it OUT. <w>
How brown COW?
Easy squeezy.
NOD2 --- 1420 hits - pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=nod2
Shall we start with #1?
OK...
http://www.ncbi.nlm.nih.gov/pubmed/20981205
Gut Liver. 2010 Sep;4(3):295-306. Epub 2010 Sep 24.
The role of bacteria in the pathogenesis of inflammatory bowel
disease.
Friswell M, Campbell B, Rhodes J.
Gastroenterology Research Unit, University of Liverpool School of
Clinical Sciences, Liverpool, UK.
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) have features that
suggest bacterial involvement, and all genetic models of inflammatory
bowel disease (IBD) require the presence of commensal bacteria. CD is
associated with innate immune response genes such as NOD2/CARD15 and
the autophagy genes ATG16L1 and IRGM. However, IBD responds to
immunosuppression, suggesting that any bacteria involved are not
acting as conventional pathogens. Molecular techniques are rapidly
advancing our knowledge of the gut microbiota. In CD there is reduced
diversity, and notably a reduction in the probiotic Faecalibacterium
prausnitzii, the presence of which in the terminal ileum is associated
with a reduced risk of recurrence following surgery. There is also a
consistent increase in mucosa-associated Escherichia coli with an
"adherent and invasive" phenotype, which allows them to replicate
inside macrophages and induce granulomas. Speculation that CD could be
caused by the Mycobacterium avium subspecies paratuberculosis (MAP)
continues. The response to antitumor necrosis factor treatments
suggests that, if relevant at all, MAP is not acting as a conventional
pathogen. However, there is increased colonization by MAP in CD, and
there is evidence that it could have an indirect effect mediated by
the suppression of macrophage function. UC relapse is frequently
associated with infection by pathogens, but there is less evidence for
involvement of a specific bacterial species. Poor barrier integrity
followed by an inflammatory reaction to bacterial components, with
chronicity maintained by an autoimmune process, seems a plausible
pathogenic model. Bacterial theories of pathogenesis are now becoming
testable by targeted therapeutic interventions.
PMID: 20981205
#2 in this serach also looks like something i should also read:
http://www.ncbi.nlm.nih.gov/pubmed/20980996
Control of intestinal Nod2-mediated peptidoglycan recognition by
epithelium-associated lymphocytes.
Duerr CU, Salzman NH, Dupont A, Szabo A, Normark BH, Normark S,
Locksley RM, Mellroth P, Hornef MW.
Mucosal Immunol. 2010 Oct 27.
PMID: 20980996
So what is that stuff?
Which? LOL
This one, the gut flora deniZEN that is GOOD for YOU crohn folk:
http://en.wikipedia.org/wiki/Faecalibacterium_prausnitzii
Faecalibacterium prausnitzii is a commensal bacterium found in the
human gut. It is a member of the division Firmicutes. [1]
Recent medical research has suggested that low levels of F.
prausnitzii may be associated with Crohn's Disease. [2] [3]
OK so why is it LOW?
How do you TOP it OFF?
Is it MAP that rules the ratio of this gut critter?
http://en.wikipedia.org/wiki/Mycobacterium_avium_subspecies_paratuberculosis
Mycobacterium avium subspecies paratuberculosis (MAP) is an obligate
pathogenic bacterium in the genus Mycobacteria.[1] It is often
abbreviated M. paratuberculosis, M. avium sub. paratuberculosis or
MAP. The type strain is ATCC 19698 (equivalent to CIP 103963 or DSM
44133).[2]
<randall note: hey! no wonder you HATE milk. LOL it's like vamPire
stuff full of MAP craP....YIKEs...>
OK so eat artichoke hearts and avoid the milkish EVILs like crazy?
Gooble up the galactose gosPel or else evil ghouls will get you
...
That's more then a gut hunch btw...which whey?
Sweet whey. LOL
http://en.wikipedia.org/wiki/Oligosaccharides
Fructooligosaccharide
http://en.wikipedia.org/wiki/Fructooligosaccharide
Galactooligosaccharides
http://en.wikipedia.org/wiki/Galactooligosaccharides
-----------------------
BACK to evil MAP...
Pathophysiology
MAP causes Johne's disease in cattle and other ruminants, and it has
long been suspected as a causative agent in Crohn's disease in
humans[3]; this connection is controversial.[4]
Recent studies have shown that MAP present in milk can survive
pasteurization, which has raised human health concerns due to the
widespread nature of MAP in modern dairy herds. MAP survival during
pasteurization is dependent on the D72C-value of the strains present
and their concentration in milk. It is heat resistant and is capable
of sequestering itself inside white blood cells, which may contribute
to its persistence in milk. It has also been reported to survive
chlorination in municipal water supplies.
Even though MAP is hardy, it is slow growing and fastidious, which
means it is difficult to culture. Many negative studies for MAP
presence in living tissue, food, and water have used culture methods
to determine whether the bacteria are present. Due to recent advances
in our knowledge of the bacterium, some or all of these studies may
need to be re-evaluated on the basis of culture methodology.
MAP infections, like with most mycobacteria, are difficult to treat.
It is not susceptible to antituberculosis drugs (which can generally
kill Mycobacterium tuberculosis), but can only be treated with a
combination of antibiotics such as rifabutin and a macrolide such as
clarithromycin. Treatment regimens can last years.[5][6]
Crohn's disease
MAP is recognized as a multi-host mycobacterial pathogen with a proven
specific ability to initiate and maintain systemic infection and
chronic inflammation of the intestine of a range of histopathological
types in many animal species, including primates.[7]
On the assumption that MAP is a causative agent in Crohn's disease,
the Australian biotechnology company Giaconda is seeking to
commercialize a combination of rifabutin, clarithromycin, and
clofazimine as a potential drug therapy, called Myoconda, for Crohn's.
As of April 2007, Giaconda received United States FDA IND approval for
a new Phase 2/3 trial.[8].
MAP has been found in larger numbers within the intestines of Crohn's
disease patients[9] than those with ulcerative colitis and healthy
controls.
<snip>
OK so these GOOD dudes your lacking in include the LABs
SEE
http://en.wikipedia.org/wiki/Firmicutes
[...] Genera
While there are currently more than 274 genera within the Firmicutes
phylum, notable genera of Firmicutes include:
Bacilli, order Bacillales
Bacillus
Listeria
Staphylococcus
Bacilli, order Lactobacillales
Enterococcus
Lactobacillus
<sniP>
LABs are GOOD and one way or NOT the evil milkish udder you have to
FEED them.
Right rosco.
I already posted the galactose in this thread?
right.... LOL
also
http://en.wikipedia.org/w/index.php?title=Mannooligosaccharide&action=edit&redlink=1
Mannooligosaccharide
How'd we go full circle?
I'm use to it.
http://en.wikipedia.org/wiki/Gut_flora#Acquisition_of_gut_flora_in_human_infants
http://en.wikipedia.org/wiki/Gut_flora#Carbohydrate_fermentation_and_absorption
So how do you knock down MAP
EASY breezy.
Take huge amounts of NAC and then top off with iodine and the usual
line up.
I'd also top off with vitamin B1 and zinc.
I did this recently and it significantly helped digestion functions.
YKW was
right.
I can really pig out... but body odor goes up. LOL
So there is a downside to being able to eat the kitchen sink and
digest it. <w>
OK, i feel like i'm missing something?
What?
I don't know.
But taking NAC to make phase II detox enzymes like GPX and SOD
is key to backing down the monkey business with MAP.
So?
Well you need Cruciferous vegetables
http://en.wikipedia.org/wiki/Cruciferous_vegetables
And then you can cut the mustard
http://en.wikipedia.org/wiki/Brassicaceae
These ARE the ones
http://en.wikipedia.org/wiki/Brassica
Can you eat these dudes?
[...] Food
Almost all parts of some species or other have been developed for
food, including the root (rutabaga, turnips), stems (kohlrabi), leaves
(cabbage, brussels sprouts), flowers (cauliflower, broccoli), and
seeds (many, including mustard seed, oilseed rape).
I find Sulforaphane to be very beneficial for health.
You might go so far as germinating broccoli sprouts?
EAT them as their Sulforaphane levels are off the chart.
http://en.wikipedia.org/wiki/Sulforaphane
[...] Occurrence and isolation
Sulforaphane was identified in broccoli sprouts, which, of the
cruciferous vegetables, have the highest concentration of sulforaphane.
[1] It is also found in brussel sprouts, cabbage, cauliflower, bok
choy, kale, collards, chinese broccoli, broccoli raab, kohlrabi,
mustard, turnip, radish, arugula, and watercress.
[edit] Possible medicinal properties
Consumption of broccoli sprouts has shown to be potentially effective
at inhibiting Helicobacter pylori growth,[2][3] with sulforaphane
being at least one of the active agents.[4][5]
Sulforaphane and dietary consumption of cruciferous vegetables are
known to affect the action of drug-metabolizing enzymes in vitro and
in preliminary human studies.[6] Although no side effects or direct
drug interactions have been reported as of 2008, people taking
prescription drugs are advised to consult a doctor before taking
sulforaphane or broccoli-sprout extracts.
The possible anticancer activity of sulforaphane may be related to the
induction of phase-II enzymes of xenobiotic transformation (such as
quinone reductase and glutathione S-transferase), and enhancing the
transcription of tumor suppressor proteins, possibly via inhibitory
effects on histone deacetylase.[citation needed]
Sulforaphane and diindolylmethane (another compound from Brassica
vegetables) inhibit cancer growth in vitro and in experimental animals.
[citation needed]
When applied topically, sulforaphane may protect skin against UV
radiation damage, and thus potentially against cancer.[7] Sulforaphane
may inhibit histone deacetylase (HDAC) activity.[8]
Sulforaphane may protect the heart from inflammation that can lead to
atherosclerosis.[9]
<sniP>
Man i'm making myself hungry
And believe it or not we can relate that to SUSAN.
My sweet susan is so precious.
She keeps me focused on stress and all things hpa-axis related.
So?
Think now.
Hunger is Hypothalamus related:
http://en.wikipedia.org/wiki/Hypothalamus
http://en.wikipedia.org/wiki/Hungry
Hunger is a feeling experienced when one has a need to eat food.
Hunger is different from appetite, the desire (rather than need) to
eat food. Satiety is the absence of hunger. The often unpleasant
feeling of hunger originates from the hypothalamus releasing hormones
that target receptors in the liver. Although a healthy, well-nourished
individual can survive for weeks without food intake,[1] the sensation
of hunger typically manifests after only a few hours without eating
and is generally considered to be unpleasant.
So not only are we hungry for substance to feed the body but also the
IDEAL that it can heal and
make us FEEL GOOD.
Which means we need to FAST to obtain health and a born again colon.
LOL
What happens when you guys FAST?
Can you break that fast with these veggies and some GOOD carbs like
sweet beets?
And can you see putting some GOOD LAB (lactic acid bacteria) up your
yin yang
after that fast?
Oh well..
Sounds good on paper.
Have a nice life.
It only took me more then half of one to find it.
randall... thoughts of a MAD MAN....(mad is madison as in avenue btw)
jay
> > in monocytes with 2 mutated NOD2 alleles
> > is likely to set a new link between NOD2 mutations
> > and the inflammatory mechanisms underlying CD.
>
"sources of galactose may include sugar beets, gums, seaweed,
flaxseed, mucilage, whey, some vegetables, etc"
I imagine that beets will be quite high in sucrose relative to
galactose.
> The role of bacteria in the pathogenesis of inflammatory bowel disease.
> ... Poor barrier integrity
> followed by an inflammatory reaction to bacterial components, with
> chronicity maintained by an autoimmune process, seems a plausible
> pathogenic model. Bacterial theories of pathogenesis are now becoming
> testable by targeted therapeutic interventions.
>
> Recent medical research has suggested that low levels of F.
> prausnitzii may be associated with Crohn's Disease.
>
> Faecalibacterium prausnitzii is a commensal bacterium found in the
> human gut. It is a member of the division Firmicutes....
>
> While there are currently more than 274 genera within the Firmicutes
> phylum, notable genera of Firmicutes include:
> ... Lactobacillus ...
>
> OK so why is it LOW?
> OK so these GOOD dudes your lacking in include the LABs
> LABs are GOOD ... you have to FEED them.
> How do you TOP it OFF?
Besides your whey/galactose, I suspect soluble fibers also.
Pubmed abstract 17127304 seems to suggest glutamine!
And therefore cabbage & kimchi?
> Mycobacterium avium subspecies paratuberculosis (MAP) is an obligate
> pathogenic bacterium in the genus Mycobacteria....
> Recent studies have shown that MAP present in milk can survive
> pasteurization...
> MAP has been found in larger numbers within the intestines of Crohn's
> disease patients than those with ulcerative colitis and healthy controls.
>
> no wonder you HATE milk.
> LOL it's like vamPire stuff full of MAP craP....YIKEs...
> OK so eat artichoke hearts and avoid the milkish EVILs like crazy?
>
> Take huge amounts of NAC and then top off with iodine
> and the usual line up.
>
> I'd also top off with vitamin B1 and zinc.
> I did this recently and it significantly helped digestion functions.
>
> Well you need Cruciferous vegetables ...
> I find Sulforaphane to be very beneficial for health.
> You might go so far as germinating broccoli sprouts?
> EAT them as their Sulforaphane levels are off the chart.
>
> My sweet susan is so precious.
> She keeps me focused on stress and all things hpa-axis related.
Is hpa-axis related to vagus nerve, yoga, deep breathing, etc?
> ...Which means we need to FAST to obtain health and a born again colon.
> What happens when you guys FAST?
It helps me lower inflammation and allergies.
> Can you break that fast with these veggies
> and some GOOD carbs like sweet beets?
> And can you see putting some GOOD LAB (lactic acid bacteria) ...
>
> Have a nice life.
> It only took me more then half of one to find it.
>
> randall... thoughts of a MAD MAN...
Last Sunday, I did the implant.
All day I had painful gas.
On Monday, there was no BM.
But Tuesday, thing resumed and stools firmed up a bit,
an effect which has persisted thus far.
My current diet is:
1 cup of home-made whey upon waking with some inulin.
Fruits & salad for lunch and dinner consisting of lettuce, cabbage,
broccoli, celery, jicima,
onion, garlic, ginger, turmeric, chili with some home-made kimchi or
yogurt.
At night, yogurt or milk (thoroughly boiled).
Do you recommend changes?
Supplements: Usually psyllium, probiotics, NAC, carnitine & vitamins.
Sometimes FO, taurine & licorice.
Besides changes in bm, I'll be watching for reduction in colon
soreness, trigger fingers, joints & nerve inflammation, high
cholesterol levels and vitiligo. Let's see where a MAD MAN lead me :)
jay
> > She keeps me focused on stress and all things hpa-axis related.
>
> Is hpa-axis related to vagus nerve, yoga, deep breathing, etc?
Some yogis in India have been claiming that deep-breathing exercises
will cure just about everything. Below abstract may give some
credibility to their claims:
Activation of the cholinergic anti-inflammatory system by nicotine
attenuates neuroinflammation via suppression of Th1 and Th17
responses.
The alpha7 nicotinic acetylcholine receptor (nAChR) was recently
described as an anti-inflammatory target in both macrophages and T
cells. Its expression by immune cells may explain the epidemiological
data claiming a negative link between cigarette smoking and several
inflammatory diseases. In this study, we determined the immunological
effects of alpha7 nAChR activation by nicotine. Our results indicate
that the alpha7 nAChR is expressed on the surface of CD4(+) T cells
and that this expression is up-regulated upon immune activation.
Nicotine reduced T cell proliferation in response to an
encephalitogenic Ag, as well as the production of Th1 (TNF-alpha and
IFN-gamma) and Th17 cytokines (IL-17, IL-17F, IL-21, and IL-22). IL-4
production was increased in the same setting. Attenuation of the Th1
and Th17 lineages was accompanied by reduced T-bet (50%) and increased
GATA-3 (350%) expression. Overall, nicotine induced a shift to the Th2
lineage. However, alpha7(-/-)-derived T cells were unaffected by
nicotine. Furthermore, nicotine reduced NF-kappaB-mediated
transcription as measured by IL-2 and IkappaB transcription. In vivo,
administration of nicotine (2 mg/kg s.c.) suppressed the severity of
CD4(+) T cell-mediated disease experimental autoimmune
encephalomyelitis. alpha7(-/-) mice were refractory to nicotine
treatment, although disease severity in those animals was reduced, due
to impairment in Ag presentation. Accordingly, CD4(+) and CD11b(+)
cells infiltration into the CNS, demyelination, and axonal loss were
reduced. Our data implicate a role for the alpha7 nAChR in immune
modulation and suggest that alpha7 nAChR agonists may be effective in
the treatment of inflammatory disorders. PMID: 19846875
randall
Hey,
This is sort of a little follow up to my last post just now.
A fun trial to run would be get ten yogi masters
and inject sFB in to their ileum's and induce
an autoimmune condition.
Or do it with RATs? LOL
And then see if the yogi's can meditate the effects
downstream away?
Now.......... that is a meaningful trial that someone in INDIA
could run. They have a billion people there.
Certainly some yogi's could be INDUCED in to this
trial that only an insane person could think up?
randall... damn i gues i do have an insane streak...
eat insane steaks? a mistake? PORK isn't in
it's a sin and not ZEN. <G>
randall
Hey me,
I guess you sPelled gues wrong? LOL
I gues you should read before willy nilly sending things?
I guess....
But what comes uP?
So i went and read the one i posted just previously to this one.
And read the ONE return (1 out of 4 in the P NG) on aldous huxley that
i didn't post by ED
Anderson to evetsm
<note: i did read the first by me as i wanted to see what i posted for
the here and now then and when>
Not only did i realize how much i liked ALL of these people,
i wonder if i was.... a..... well you know....me. LOL
Anyway, this is ED's sign off from that post... ten times longer then
most of mine. <G>
I'm so proud of HIM. "?"
-- Ed "?" Anderson
"A fanatic is one who can't change his mind and won't change the
subject."
-- Winston Churchill
"Defined in psychological terms, a fanatic is a man who consciously
overcompensates a secret doubt."
-- Aldous Huxley
"Fanaticism consists in redoubling your efforts when you have
forgotten
your aim."
-- George Santayana
"From fanaticism to barbarism is only one step."
-- Denis Diderot
"Get your facts first; then you can distort them as you please."
-- Mark Twain
"Great ideas need landing gear as well as wings."
-- C. D. Jackson
"He who knows only his own side of the case, knows little of that."
-- John Stuart Mill
"He who will not reason is a bigot; he who cannot is a fool; and he
who
dares not, is a slave."
-- William Drummond
"I used to be disgusted; now I try to be amused."
-- Elvis Costello
"The power of accurate observation is commonly called cynicism by
those
who have not got it."
-- George Bernard Shaw
"To be sure of hitting the target, shoot first, and call whatever you
hit
the target."
-- Ashleigh Brilliant
"I hate quotations. Tell me what you know."
-- Ralph Waldo Emerson
<snip>
Do you suPPose that ED thinks stever or gary is a fanatic.
http://en.wikipedia.org/wiki/Fanaticism
Do you suPPose or do i that susan thinks that about me?
YES... LOL
And that is NO GUESS.
What?
a fan (in the) atic
The attic being in the here and now and unused space in your brain
where you store all the crap you don't use?
So?
u PUT a FAN in that sPace? Lower the heat and the whole structure
cools down?
randall... right... it's all LEFT over craP. LOL
ps- i'm not going to beat ED's sign off quotes now, just guessing?
Kofi
<df97867b-1ec9-4095...@e14g2000yqe.googlegroups.com>,
jay <jaym...@hotmail.com> wrote:
You gentlemen are forgetting that self-tolerance and innate immunity
appear to be the same thing. TLR4 is necessary for both innate defense
against pathogens and self-tolerance. When NOD2 damages the innate
response to bacteria it's also damaging an important part of the
complement cascade (coordinated via sympathetics) that defends self
tissue via IL-10.
What's the problem here? If you limit inflammation the wrong way, you
give these pathogens a leg up and make the condition worse. TNF-alpha
therapy isn't necessarily limiting inflammation, by the way, it's
restoring certain vitamin D pathways to full function - but even here
you have issues. Witness the risks of cancer and specific, rare
infections when antagonizing TNF-alpha. You have to understand these
interactions.
Consider:
- Tregs both provent autoimmunity and certain classes of latent viral
infection.
- NK cells appear to both attack pathogens/cancer directly without
antibody involvement and protect against M.S. in the CNS.
- Macrophages both trigger inflammation and release growth factors to
repair inflammatory damage. Given the presence of antibodies to GM-CSF,
they're underfunctional in Crohn's.
Once autoimmunity steps in, the system can get tied into knots. For
instance, if strep generates antibodies against dopamine receptors, that
interferes with the methods of sympathetic tolerance.
randall
> In article
> <df97867b-1ec9-4095-9f46-b7b6d94a8...@e14g2000yqe.googlegroups.com>,
>
> jay <jaym1...@hotmail.com> wrote:
> > >> LPS -> TLR4 -> P38 MAPK -> SP1 -> IL10.
>
> > > But the stuff that grows the GOOD FLORA (microbiota) in your colon
> > > is GALACTOSE.
> > > Your body doesn't digest it so it goes right through you and
> > > then the GOOD FLORA is FED.
>
> > I thought that in a lactose tolerant person, lactose is split into
> > glucose and galactose by lactase. And the liver converts galactose to
> > glucose.
>
> > It seems, the following pathway
> > LPS > TLR4 > APC/DC > IL23 (p19 & p40) > IL23R of TH17 > IL17
> > and variants of L12B(encodes p40) & IL23R can produce chronic
> > inflammation.
> > If so, we need a majic herb that bind p40s or are the lactobacteria
> > already doing this :)
>
> You gentlemen are forgetting that self-tolerance and innate immunity
> appear to be the same thing.
I'M All wheys forgetting the sweetness of LIFE, though i don't MEAN
too....
Such HAD BEEN my experience and sadly continues.
BUT, If my self tolerance (genetic makeup?) slash innate immune
(genes - HLA/HLC MHC) system allowed me
to BECOME autoimmune then i guess so.
HOW do THEY (the ones who lost eden) find their way (sweet whey) back
to NORMAL ville?
EDEN the state of mind isn't EASY... the path to heaven is narrow and
the path to perdition is a super highway. LOL
I NOW KNOW based on my Gi tract experiments that DAN LITTMAN
is correct and SFB are INDUcTING Th17 cells that perpetuate
autoimmunity.
For that alone DAN deserves the nobel prize.
But he hasn't drunken the SFB in the manner that marshall/robin warren
did the h. pylori
http://en.wikipedia.org/wiki/Barry_Marshall
Why bother? He has me with amPle amounts of SFB to run that L.
Plantarum trial to prove
his SFB inducts Th17 theory.
46 hits/ littman sfb Th17 - p ng
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=littman+Th17+SFB
And it is self folerance then an implant of good LAB allows me to
reestablish homeostasis via a diet over the next
30 days?
If so then you know.
But say i get some de novo psoriasis via STREP ( it happens for
most of us btw) and then i'm pumped with EVIL Rx antibiotics.
If evil anti biosis only killed the evil pathogens then it would be
LAB. LOL
Can you imagine the long term damage to my GOOD (LAB) GUT flora via
extended antibiotics?
Yikes.
It's taken for ever for the FACTs t become clear.
http://www.eurekalert.org/pub_releases/2010-11/sfgm-ahl110110.php
Antibiotics have long-term impacts on gut flora
Short courses of antibiotics can leave normal gut bacteria harbouring
antibiotic resistance genes for up to two years after treatment, say
scientists writing in the latest issue of Microbiology, published on 3
November.
The researchers believe that this reservoir increases the chances of
resistance genes being surrendered to pathogenic bacteria, aiding
their survival and suggesting that the long-term effects of antibiotic
therapy are more significant than previously thought.
Antibiotics that are prescribed to treat pathogenic bacteria also have
an impact on the normal microbial flora of the human gut. Antibiotics
can alter the composition of microbial populations (potentially
leading to other illnesses) and allow micro-organisms that are
naturally resistant to the antibiotic to flourish.
The impact of antibiotics on the normal gut flora has previously been
thought to be short-term, with any disturbances being restored several
weeks after treatment. However, the review into the long-term impacts
of antibiotic therapy reveals that this is not always the case.
Studies have shown that high levels of resistance genes can be
detected in gut microbes after just 7 days of antibiotic treatment and
that these genes remain present for up to two years even if the
individual has taken no further antibiotics.
The consequences of this could be potentially life-threatening
explained Dr Cecilia Jernberg from the Swedish Institute for
Infectious Disease Control who conducted the review. "The long-term
presence of resistance genes in human gut bacteria dramatically
increases the probability of them being transferred to and exploited
by harmful bacteria that pass through the gut. This could reduce the
success of future antibiotic treatments and potentially lead to new
strains of antibiotic-resistant bacteria."
The review highlights the necessity of using antibiotics prudently.
"Antibiotic resistance is not a new problem and there is a growing
battle with multi-drug resistant strains of pathogenic bacteria. The
development of new antibiotics is slow and so we must use the
effective drugs we have left with care," said Dr Jernberg. "This new
information about the long-term impacts of antibiotics is of great
importance to allow rational antibiotic administration guidelines to
be put in place," she said.
<sniP>
But when i did the implant of good LAB i took my psor skin condition
down to almost ZERO.
Surely as snot, over the last decade i've stayed very very MILD psor
WISE.
It was almost heaven.
That would take a CURE btw. LOL
Can you tell me i'm NOT at HEAVEN's DOOR?
The fanatic word comes to mime. LOL
And yes i'll try to maintain the correct sef tolerances.
And maintain quality of life in the scheme of LONG TERM Quanitity of
high quality LIFE. :)
why do i post on longevity folks like jeanne calment?
Do you try to BE like her?
And if NOT then WHY NOT?
She's the zenyatta of the human world for longevity:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=calment
Well that metaphor does need a tweak so to sPeak. <w>
http://en.wikipedia.org/wiki/Zenyatta
OK...
Because i'm not gonna LIVE that long (122 y/o) if my quality isn't
maintaining an enjoyment commensurate with the EDEN
concepts.
http://en.wikipedia.org/wiki/Garden_of_eden
Yet i could replace the flaming sword i suPPose?
http://en.wikipedia.org/wiki/Uriel
With what?
Got it.
http://en.wikipedia.org/wiki/Light_saber
Jedi vs sith?
OK or simply yin yang isms?
Soros and obama socialism being black with the white dot being
capitalism? LOL
Unless soros is REALLY really the sororific spawn or destructor of
capitalism?
The rise of A NEW paternalistic western socialism?
I don't think so, it being more maternal (dark or earth like) in my
interpretations. <g>
Or is soros only going to GAME the capital markerts and make $25B on
the side?
How much does it cost to sow the seeds of deconstruction of one system
in the minds of nit wit econ's?
http://www.washingtonsblog.com/2010/04/is-it-time-for-debt-jubilee.html
Friday, April 9, 2010
Debt Repudiation: Good Idea or Bad Idea?
===========
OK econ 101 over for NOW.
I'll report my feelings tomorrow...
Will the SUN Come out tomorrow?
Ask annie?
"Annie" (1982) - Tomorrow
http://www.youtube.com/watch?v=Yop62wQH498
I might LOVE you tomorrow?
If the SUN (vitamin D3 from ~309 nm nbUVB's) does shine. LOL
Your only a DAY AWAY.
SWEET... whey each and every day. Is more like it annie. LOL
> TLR4 is necessary for both innate defense
> against pathogens and self-tolerance. When NOD2 damages the innate
> response to bacteria it's also damaging an important part of the
> complement cascade (coordinated via sympathetics) that defends self
> tissue via IL-10.
SO, you know what happens. Big DEAL, the real scietists didn't even
know
this when i almost CURED myself.
If only i had known exactly how to implant and how to culture the
factors
that will create the CURE... <W>
And new stuff is coming on line as we speak?
Speak DOG... speak:
& randall tar baby chimes in:
http://www.eurekalert.org/pub_releases/2010-11/sfgm-ahl110110.php
Whoops did that one TODAY.
I want this udder one today
OK but don't JACK ME uP NOW?
OK i won't. LOL
STAT go to the ER...cure those. endoplasmic reticulum's with NAC
(glutathione) STAT. <G>
wow... 11 hits... more then i would have BET... T-Bet? NO... you
bet. LOL
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=Endoplasmic+reticulum+glutathione&qt_g=Search+this+group
http://www.eurekalert.org/pub_releases/2010-11/foas-sua110110.php
Scientists uncover a genetic switch that turns immune responses on and
off
New research in the FASEB Journal suggests that a novel negative
regulator called eye transformer impacts JAK/STAT-signaling pathway
response with microbial challenge in fruit flies
Scientists are keeping their eye on a new discovery published in the
November 2011 print issue of the FASEB Journal (http://www.fasebj.org)
that explains what causes some genes to go out of control. Scientists
have identified a "cellular switch," called eye transformer, that
controls the flow of information from chemical signals outside of the
cell to genes in the cell nucleus. This study demonstrates that when
eye transformer is turned off, the information pathway it controls
(the "JAK/STAT pathway") hyper-activates. Because this pathway exists
in humans and is involved in many conditions such as cancer, severe
immune deficiencies, autoimmune diseases, and allergies, this
discovery reveals a new and potentially important drug target for
these conditions.
"We hope that our study will open new horizons for researchers
studying mammalian JAK/STAT signaling which eventually leads to better
understanding how mammalian JAK/STAT signaling is regulated," said
Mika Rämet, Ph.D., co-author of the study from the Institute of
Medical Technology at the University of Tampere in Finland. "We hope
that this information can be then used in developing better treatments
for diseases that are influenced by malfunctioning JAK/STAT
signaling."
To make this discovery, Rämet and colleagues "silenced" all of the
fruit fly genes one by one using RNAi-based screening methods in
cultured Drosophila (fruit fly) cells and then analyzed which genes
were important for JAK/STAT signaling. They identified five novel
regulators, one of which was a negative regulator of eye transformer
that proved to negatively regulate the JAK/STAT response during
microbial challenge. Further research showed that suppression of eye
transformer expression in the eyes of fruit flies by in vivo RNAi
causes hyper-activation of JAK/STAT signaling indicated by drastic eye
overgrowth when JAK/STAT signaling was activated.
"We tend to treat immune diseases after the inflammation switch has
been turned on," said Gerald Weissmann, M.D., Editor-in-Chief of the
FASEB Journal and a past president of the American College of
Rheumatology. "This study sheds new light on how we might to control
diseases like rheumatoid arthritis or lupus by keeping our hands on
the switch."
<sniP>
http://www.ncbi.nlm.nih.gov/pubmed/20624926
FASEB J. 2010 Jul 12. [Epub ahead of print]
Eye transformer is a negative regulator of Drosophila JAK/STAT
signaling.
Kallio J, Myllymäki H, Grönholm J, Armstrong M, Vanha-Aho LM, Mäkinen
L, Silvennoinen O, Valanne S, Rämet M.
*Laboratory of Experimental Immunology andLaboratory of Molecular
Immunology and Cytokine Receptor Signaling, Institute of Medical
Technology, University of Tampere, Tampere, Finland; andDepartment of
Pediatrics, Tampere University Hospital, Tampere, Finland.
Abstract
JAK/STAT signaling pathway is evolutionarily conserved and tightly
regulated. We carried out a reporter-based genome-wide RNAi in vitro
screen to identify genes that regulate Drosophila JAK/STAT pathway and
found 5 novel regulators. Of these, CG14225 is a negative regulator
structurally related to the Drosophila JAK/STAT pathway receptor
Domeless, especially in the extracellular domain, and to the mammalian
IL-6 receptor and the signal transducer gp130. CG14225
coimmunoprecipitates with Domeless and its associated kinase hopscotch
in S2 cells. CG14225 RNAi caused hyperphosphorylation of the
transcription factor Stat92E in S2 cells on stimulation with the
Drosophila JAK/STAT pathway ligand unpaired. CG14225 RNAi in vivo
hyperactivated JAK/STAT target genes on septic injury and enhanced
unpaired-induced eye overgrowth, and was thus named the eye
transformer (ET). In the gastrointestinal infection model, where JAK/
STAT signaling is important for stem cell renewal, CG14225/ET RNAi was
protective in vivo. In conclusion, we have identified ET as a novel
negative regulator of the Drosophila JAK/STAT pathway both in vitro
and in vivo, and it functions in regulating Stat92E phosphorylation.-
Kallio, J., Myllymäki, H., Grönholm, J., Armstrong, M., Vanha-aho, L.-
M., Mäkinen, L., Silvennoinen, O., Valanne, S., Rämet, M. Eye
transformer is a negative regulator of Drosophila JAK/STAT signaling.
PMID: 20624926
I need to take the time to grok this in light of erin and her minocin
and antibiotics vs. marshall protocols and
oral D3 with nb-uvb's and all in the light of SFB in the ileum no
doubt. LOL
13 hits - grok - p ng:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=grok
OK STAT find the JAK. LOL
55 hits for jak stat - p ng
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=jak+stat
So why wouldn't i push LAB as i knew the cure would COME from IT.
Antibiotics being the JACK HAMMER.
But a tool is a tool and has it's place.
Give me the jack hammer if i'm gonna die?
I'll try. LOL
In the case of autoimmunity and psor skin i'll take the sweet whey and
go with the LAB.
>
> What's the problem here? If you limit inflammation the wrong way, you
> give these pathogens a leg up and make the condition worse.
Antibiotics make most of US with the GENEs WORSE. OVER TIME...
There is the reboundusmaximus effects.
Yet they didn't know that TILL NOW?
See the link from TODAY
Eureka
http://www.eurekalert.org/pub_releases/2010-11/sfgm-ahl110110.php
While i was told that LAB would cure me back in the early 70's it
wasn't till i implanted them 1999 that the odyssesy became REAL.
I could return FROM itchy KA so to sPeak.
That metaphor being:
http://en.wikipedia.org/wiki/Ithaca
[..] Modern Ithaca is generally identified with Homer's Ithaca, the
home of Odysseus, whose delayed return to the island is the subject of
the Odyssey.
He sort of looks like me when i was 21. LOL
http://en.wikipedia.org/wiki/Odysseus
Hey almost forgot the drd4 liberal gene from ucsd JH Fowler?
Nope not in pubmed yet
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fowler%20JH%22%5BAuthor%5D
> TNF-alpha
> therapy isn't necessarily limiting inflammation, by the way, it's
> restoring certain vitamin D pathways to full function
LOOK if the marshal protocols worked i'd BE CLEAR.
Why NOT CLEAR the SFB and then vitamin D3 from the SUN
and FOOD?
Otherwise with an ileum supporting SFB the D3 only pushes
more inflammation for psoriatics.
And it confounds calcium (calmodulin ca2+) and the entire inflammatory
pathways.
http://en.wikipedia.org/wiki/Calmodulin#Function
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=psoria*+AND+calmodulin
760 hits
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=psoria*+AND+calmodulin
Only four hits for crohn's and ca2+
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's+AND+calmodulin
I don't have the time to review aNY of these. So?
Wednesday?
> - but even here
> you have issues. Witness the risks of cancer and specific, rare
> infections when antagonizing TNF-alpha. You have to understand these
> interactions.
I DO in sPades thank you very much.
>
> Consider:
>
> - Tregs both provent autoimmunity and certain classes of latent viral
> infection.
OK and they skew one to Th2 and cancer and aids/hiv.
I don't want that many of them treg's. LOL
>
> - NK cells appear to both attack pathogens/cancer directly without
> antibody involvement and protect against M.S. in the CNS.
>
> - Macrophages both trigger inflammation and release growth factors to
> repair inflammatory damage. Given the presence of antibodies to GM-CSF,
> they're underfunctional in Crohn's.
>
> Once autoimmunity steps in, the system can get tied into knots. For
> instance, if strep generates antibodies against dopamine receptors, that
> interferes with the methods of sympathetic tolerance.- Hide quoted text -
>
> - Show quoted text -
Thanks,
But can you give me your trials that have controlled Th1/Th2
and how you did it?
What have you done to create a healthy milieu inside of YOU?
I went from 30-75% pasi pizza skin to under 3% pasi via LAB.
Lacti acid bacteria will upregulate IL-10 and TREG's.
They do that by keeping SFB within the limits of not inducting
excess Th17.
So?
I keep just enought SFB and Th17 to prevent cANCER.
Thusly if i live a moderate life style i'll live to 100 and
maybe.
Just maybe enjoy LIFE.
Which includes some resveratrol, kimchi et AL...
and 2 cents of sweet whey each and every day. <G>
randall... my 2 cents are worth a life time of former skin
conflix's.....
jay
> > LPS > TLR4 > APC/DC > IL23 (p19 & p40) > IL23R of TH17 > IL17
> > and variants of L12B(encodes p40) & IL23R can produce chronic
> > inflammation.
> > If so, we need a majic herb that bind p40s or are the lactobacteria
> > already doing this :)
>
> You gentlemen are forgetting that self-tolerance and innate immunity
> appear to be the same thing. TLR4 is necessary for both innate defense
> against pathogens and self-tolerance. When NOD2 damages the innate
> response to bacteria it's also damaging an important part of the
> complement cascade (coordinated via sympathetics) that defends self
If the "majic herb" simultaneously suppresses p40 & pathogens, then it
should be OK, right? According to pubmed thse include resveratrol,
butyrate, azithromycin, PPARa,d,g agonists (ie curcumin, ASA), etc.
And the following suppress Th/IL-17: apigenin, berberine, EGCG, GSE,
herbal formula 'Huo luo xiao ling dan', bifidobacterium, retinoic
acid, statins, D3, etc.
jay
> My current diet is:... whey upon waking with some inulin.
> Fruits & salad for lunch and dinner with some home-made kimchi or
> yogurt. At night, yogurt or milk (thoroughly boiled)...
A little more than a week has gone by and the positive changes in bm
have mostly held up, but I'm gonna have to stop dairy as it is
provoking my immune system and it's response is getting stronger. As a
result of yogurt before going to bed, last night I woke up with heart
pound, slight sweating, itchy sensation in my small intestines, crawly
sensation in my forearms, a mild headache and next day rectum soreness
and joints that seem to grind. All these symptom are familiar to me
and are caused by many foods but dairy and wheat are amongst the
worst. I think the kimchi will be OK. The only form of dairy that
hasn't bothered me much over the long haul has been milk-protein-free
clarified butter.
I guess my situation is somewhat similar to the NOD mouse. This mouse
has a genetic defect where insufficient IL2 leads to low levels of
TRegs and increased IL17. Per Wiki, beside T1 diabetes and cataracts,
"NOD mice are also susceptible to developing other autoimmune
syndromes, including autoimmunine sialitis, autoimmune thyroiditis,
autoimmune peripheral polyneuropathy, a systemic lupus erythematosus-
like disease that develops if mice are exposed to killed
mycobacterium, and prostatitis. The susceptibility to IDDM is
polygenic and environment exerts a strong effect on gene penetrances.
Environment including housing conditions, health status, and diet all
effect development of diabetes in the mice. For instance, NOD mice
maintained in different laboratories can have different levels of
incidence."
According to pubmed, following things can accelerate disease
development:
1. Dairy proteins
2. Wheat, gluten
3. Soy
4. Dietary AGEs
5. High n6 to n3 ratio
6. Protein-rich diets
And the following things can inhibit disease development:
1. D3
2. Low glycemic diet
3. Schistosoma mansoni egg antigens
4. Lactobacteria casei
5. Selenium
6. Retinoids
7. Various polyphenols
8. IL17 inhibitors
Skeats
Jay, Have you been checked for Coeliac/Celiac Disease? (uk/usa different
spellings)
Wheat, rye, barley gluten is in lots of products that you might not think
have it and milk products are also one of the allergens in some people.
I got diagnosed with it at the age of 65 after suffering P for 40 years.
Skeats
jay
> have it and milk products are also one of the allergens in some people.
I was never tested for Celiac, but I have been "gluten free" for over
5 years. Except on rare occasions, I don't eat out, eat processed
foods or even eat foods prepared by friends. Visiting various health-
related Usenet groups made me wary of gluten/gliadin early on.
Colonoscopy didn't show flattening of vili, at least not in terminal
ileum, but then I have heard this does not conclusively rule out
Celiac.
> I got diagnosed with it at the age of 65 after suffering P for 40 years.
Yikes, 40 years! In what other ways did it manifest itself? How much
has your P improved since diagnosis? Are you sensitive to other foods?
randall
> > > It seems, the following pathway
> > > LPS > TLR4 > APC/DC > IL23 (p19 & p40) > IL23R of TH17 > IL17
> > > and variants of L12B(encodes p40) & IL23R can produce chronic
> > > inflammation.
> > > If so, we need a majic herb that bind p40s or are the lactobacteria
> > > already doing this :)
Jay,
I'm a little skewed TOPICALLY due to the politiCOW landscaPe
recently....
The hangover from such a HUGE erection... er' election, fueled with
viagra proportions of GREEN BACKs for TV ads was disgusting.
Like a parade of MAD MEN on FULL display each and every DAY...
Disgusting..
Meg WitMAN could have given me THAT $140Million and she'd look
better today then before this erection started in the first place.
Sheeessh.... HOW much money went to RICH AD folks?
Those are MAD MEN loaded with green backs bouncing around
like human jumPing BEANs today. LOL
OK ok i'm calming DOWN.
WE've got divided gov today.
Thank the LORD. <G>
Moo, moo, i'm gonna MILK that COW right outa my HAIR.
And what's wrong with BUSHbabies, baby?
http://www.youtube.com/watch?v=GN8fs5gn_38&feature=fvw
And those commercials that demonize the demons of freedumb that
drove me ad nauseum are DONE.
Yea...
But it still goes on?
Phase II blame game continues?
And like Clinton, is Obama going back to the center?
The center for him being so far left, is still LEFT? LOL
PreziDENT oh blame ah just said his policies didn't HURT the economy?
What?
Is HE insane?
Keep it up and your time is up in two YEARs mister blame hole.
I hoPe obama doesn't hire DICK Morris. He'd take him to the middle
all right. <G>
Does obama have freudian problems with the BUSH?
Is it MOO's fault?
MILK the blame GAME is his RAP? What's truly NEXT?
Is MILK the RAP for crohn's (MAP) or does it start the fire and then
autoimmunity
takes over?
And we can say that a little endogenous endotoxins (LPS) doesn't hurt
the SKIN.
NOT for the other 90% plus part of the poopulation.
LOL i thought i'd sliP that IN. <w>
But everything is tied to the BIG OM (AUM) or Yin YANG? LOL
http://en.wikipedia.org/wiki/Aum
So the leader isn't the leader and not in the AUM mode?
No no his raP is that bush is BAD. So vote for me and my change?
Changing your MIND on the sad raP now?
He's just along for the ride?
What's his RAP?
Fist bumP? Whoop there it is?
http://www.youtube.com/watch?v=pGNbgAiSidM
Check it out. MOOOOO there it is. LOL
I hear he's going to the Taj Hotel/Mumbi at $200M a day?
That must be like 500 5 star resorts then? LOL
He'll be going MOOOOO and whooP there it is with his moo in the taj
motel? LOL
Obama can blame any little bit of dis or dat for the collapse of
capitalism.
HEY, if obama doesn't want to say the BUcK stoPs here then WHO?
Ok... it's ME. It's ALL my FAULT. I did it.
I took capitalism to it's knees and sPanked him. LOL
And that bi itch weak sister called socialism has the credit card
and is out back snorting TAX CRACK.
Nasty Pelosi go HOME.. retire... the witch of tax crack is GONE.
And that is my fault as well.
I take the BLAME 100%.
OK, now for your crohn's and my psoriasis.
I take the raP. LOL
But, but, we're on the path to being CLEAR right?
I take the rap... don't drink MOO juice. LOL
No yogurt either or don't get the butter.
Is the butter a metaphor for moo or obama?
Yikes
HARD to tell? But isn't this what the people felt obama
was doing to them?
Brando - butter scene - last tango
http://www.youtube.com/watch?v=8rpgjTNCeJI
What's the last tango for psor or crohn's?
We don't have to bind p40/IL-12 et al if we return to the GARDEN of
Eating. LOL
No herb needed.
I don't have to stuff my face with luteolin or apigenin or
sulphoraphane.
I want homeostasis FIRST and a return to EDEN and no burPs along the
way.
How?
We stop the antigen or the self antigen from calling forth Th1/Th17
skew-->IL12
Or
http://www.medpagetoday.com/MeetingCoverage/ACG/22913
[...] IL-12 drives the Th1 proliferation associated with Crohn's
disease, and IL-23 stimulates Th-17 cells, leading to production of
the proinflammatory
<sniP>
So.
HOW about LPS/SFB --> TH1 skew---SFB (ileum gut critter* pmid # below)
--->Th17 added to a lps/Th1 skew = autoimmunity
OK?
For psoriasis strep can be the trigger and for crohn's it CAN be MAP.
Right?
While TLR-4 is surely in Th1 pathway is it more then a bit player
playing a BIT?
Certainly if your skew is Th2 then this so called inflammation will
EAT the cancer or HIV virus
inside of YOU or ME.
But then we'd be skewed to FAR to Th2?
What do we DO?
Look and get what the BITs are doing or find a taxi do drop us off
back in paradise?
TLR-4 211 hits P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=tlr-4
50 hits for TLR-4 google NEWs:
http://www.google.com/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=tlr-4&tbo=u&tbs=nws:1&source=og&sa=N&tab=gn
http://en.wikipedia.org/wiki/TLR_4
Symbols TLR4; CD284; TOLL; hToll
<snip>
TLR-4 triggers MYD88-->NF-kB
http://en.wikipedia.org/wiki/NF-%CE%BAB
http://en.wikipedia.org/wiki/Innate_immune_system#Anatomical_barriers
[...] Additional defense mechanims -->
-----> http://en.wikipedia.org/wiki/Gastrointestinal_tract ---> GUT
FLORA
---> http://en.wikipedia.org/wiki/Gut_flora -->
[...] barrier effect
<randall note: leaky gut or permeable gut are barrier problem's? n'est-
ce pas ?>
The kicker on this page being:
http://en.wikipedia.org/wiki/Gut_flora#Colitis
The problem being the GIT is several distinct environs with flora
that helps or hurts.
Strep for psoriatics can and does start inside or around the tonsils.
Does that make the oral cavity the culPrit? Or another bit player?
http://en.wikipedia.org/wiki/List_of_human_flora#Gastro-intestinal_tract
Stomach - ACID pH
Small intestines - alkaline
colon - should BE slightly acidic
I suggest we follow the critters for psor and crohn's.
For YOU we use MAP
http://en.wikipedia.org/wiki/Mycobacteria
http://en.wikipedia.org/wiki/Mycobacterium_avium_paratuberculosis
http://en.wikipedia.org/wiki/Mycobacterium_avium_paratuberculosis#Crohn.27s_disease
For Psoriasis it's SFB inducting Th17 in the ileum (littman - pmid:
19836068)
http://www.ncbi.nlm.nih.gov/pubmed/19836068
Induction of intestinal Th17 cells by segmented filamentous bacteria.
SFB = segmented filamentous bacteria.
But you can argue all day it's strep if you wish.
And go fish. LOL
http://www.skinandallergynews.com/news/medical-dermatology/single-article/tonsillectomy-reduces-strep-triggered-psoriasis/03f99f6185.html
Tonsillectomy Reduces Strep-Triggered Psoriasis
<sniP>
But why not any OLD LPS hanging around the tonsils or teeth or tongue
or nasal cavity?
They are not JUST a safe harbor for strep. Plenty of critters line the
Gi tract pumPing out
endogenous endotoxins (LPS).
So?
Somehow IL-12 becomes the SHOW?
Is that due to MAP in you or streP in me?
Or is autoimmune the me or you in us doing us in and the
original trigger is simply just that and cathelicidins then decide
our autoimmune fate?
If you want to say p40 subunit is the it bit then fine.
9 hits for keywords: p40 crohn's psoria* - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=p40+crohn's+psoria*
69 hits p40 AND psoria* -pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=p40+psoria*
50 hits: crohn's p40
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=p40+crohn's
P40 is IL-12 subunit beta
http://en.wikipedia.org/wiki/Interleukin-12_subunit_beta
Symbols IL12B; CLMF; CLMF2; IL-12B; NKSF; NKSF2
Subunit beta of interleukin 12 (also known as natural killer cell
stimulatory factor 2, or cytotoxic lymphocyte maturation factor 2,
p40) (human gene name IL12B) is a subunit of human interleukin 12.
<sniP>
http://en.wikipedia.org/wiki/Interleukin_12#IL-12_and_autoimmunity
Interleukin 12 (IL-12) is an interleukin that is naturally produced by
dendritic cells[1], macrophages and human B-lymphoblastoid cells
(NC-37) in response to antigenic stimulation.
[...] IL-12 is composed of a bundle of four alpha helices. It is a
heterodimeric cytokine encoded by two separate genes, IL-12A (p35) and
IL-12B (p40).
http://en.wikipedia.org/wiki/Interleukin_12#Functions
IL-12 is involved in the differentiation of naive T cells into Th0
cells which will further develop into either Th1 cells or Th2 cells.
It is known as a T cell stimulating factor, which can stimulate the
growth and function of T cells. It stimulates the production of
interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) from
T and natural killer (NK) cells, and reduces IL-4 mediated suppression
of IFN-γ. T cells which produce IL-12 have a coreceptor, CD30, which
is associated with IL-12 activity.
[...] http://en.wikipedia.org/wiki/Interleukin_12#Signal_transduction
IL-12 binds to the IL-12 receptor, which is a heterodimeric receptor
formed by IL-12R-β1 and IL-12R-β2. IL-12R-β2 is considered to play a
key role in IL-12 function, since it is found on activated T cells and
is stimulated by cytokines that promote Th1 cells development and
inhibited by those that promote Th2 cells development. Upon binding,
IL-12R-β2 becomes tyrosine phosphorylated and provides binding sites
for kinases, Tyk2 and Jak2. These are important in activating critical
transcription factor proteins such as STAT4 which are implicated in
IL-12 signaling in T cells and NK cells. This pathway is known as the
JAK-STAT pathway.[2]
http://en.wikipedia.org/wiki/Interleukin_12#IL-12_and_autoimmunity
IL-12 is linked with autoimmunity. [...] key role in induction of Th1
immune responses
<sniP>
When does lack of p40 become life threatening via sepsis (lPS- leaky
gut time)?
If your a premie then it comes uP.
http://www.ncbi.nlm.nih.gov/pubmed/20977341
J Infect Dis. 2010 Oct 13.
Profound Lack of Interleukin (IL)-12/IL-23p40 in Neonates Born Early
in Gestation Is Associated with an Increased Risk of Sepsis.
Lavoie PM, Huang Q, Jolette E, Whalen M, Nuyt AM, Audibert F, Speert
DP, Lacaze-Masmonteil T, Soudeyns H, Kollmann TR.
Child & Family Research Institute and 2Department of Pediatrics,
University of British Columbia, Vancouver, British Columbia, 3Unité
d'Immunopathologie Virale, Centre de Recherche du Centre Hospitalier
Universitaire Sainte-Justine and Departments of 4Microbiology and
Immunology, 5Pediatrics, and 6Obstetrics and Gynecology, Faculty of
Medicine, University of Montreal, Montreal, Quebec, and 7Women and
Children's Health Research Institute, University of Alberta, Edmonton,
Alberta, Canada.
Abstract
Background. Infants born prematurely are highly vulnerable to
infections and also exhibit a high susceptibility to organ damage due
to inflammation. Methods. To investigate homeostatic immune control
early in life, we used advanced multiparameter flow cytometry to
compare responses to multiple Toll-like receptor (TLR) ligands in
single cells and mononuclear cell populations in term neonates versus
preterm neonates born before 29 weeks of gestation. Results. Preterm
neonates had globally attenuated TLR-stimulated interleukin (IL)-6,
interferon-α, and, to a lesser extent, tumor necrosis factor-α
responses but demonstrated relative preservation of anti-inflammatory
IL-10 responses in monocytes and dendritic cell subtypes. Remarkably,
preterm neonates were also profoundly deficient in the common IL-12
and IL-23 cytokines' p40 subunit, which is critical for immunity
against a wide variety of microbial pathogens in mice. Consistent with
the increased susceptibility to infections resulting from the lack of
IL-12/IL-23 in human newborns, significantly lower serum p40
concentrations were observed at birth in infants who developed early-
onset sepsis. Conclusion. To our knowledge, this study is the first
detailed analysis of multiple TLR function in neonates born extremely
premature. Although attenuation of proinflammatory pathways may
protect against tissue-damaging immunity early in life, this
previously unrecognized p40 immune deficiency appears to result in
considerably increased susceptibility to infection in human preterm
newborns.
PMID: 20977341
OK... so if people with crohn's or psoriasis have a leaky gut with
excess LPS then
does IL12 p40 subunits generate in response to this?
I've always been very healthy with the exception of psor plaques on
my skin.
Only when my PASi went ballistic did i worry that my body might not
sustain LIFE and i'd DIE
earlier then planned on. Didn't want that so here i am....
Eating a YAM i'm not PooPeye the olive oil man. LOL
But that being said::: i went the gut treatment route since 1980 or so
to correct what i perceived was an imbalance in me.
Was not being breast fed it?
It may have. But i did onset after strep with de novo p as so many do.
But prior to that i was sTRONGLY Th2 as i had atopic dermatitis and
Th2 skin flares continually.
Did my GUT leaks cause the Th2 and the strep fliP floP me in to a Th1
skew?
I don't KNOW.
What i do know is a gut implant (1999) with kyo-dolphilus LABs (lactic
acid bacteria) lowered me
to a very MILD case which i could yo you (up/down) at will via diet
and supplements.
IMO an alkaline colon will trip the liver cells via the mess going
back via the hepatic
portal vein and this loop also is critical.
Thusly using the wit kit implant to return the colon to a slightly
acidic pH is key.
Is the colon the garden of eden?
In this metaphor it is.
Or in your metaphor it can be a rank sewer system and vile and
unmentionable?
So you want the sewer or garden/eden feeding back in to YOU?
And that part of the loop to the liver is one part of chronic
inflammation corrected.
Is this all compensatory for worse dis ease?
I've asked that question how many times?
154 threads or posts with keywords: compensatory aND randall - P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=randall+compensatory
#4 in this search caught my eye. The GOOD ARTICLE thread from 2002:
[...] And if P is compensatory for
| the ill effects of the auto immune system due to absorbed LPS from
| endogenous gut bacteria that is shunted by an overworked liver into
| the lymphatics then www.thewholewhey.com is the most logical whey
to
| block the translocation of bacteria into the system.
<sniP>
---------------
How does IL-10 and TNF role in this scheme?
I've thought that Th2 raise IL-10 and this would LOWER our Th1 skew.
The Th1 does bring about IFN and TNF excess and Th17 is part of this
mess.
So if i look at all of these players.
P40, TNF, IL-10 the most recent hit on pubmed is this:
http://www.ncbi.nlm.nih.gov/pubmed/20979991
Cell Immunol. 2010 Oct 8.
The role of tumor necrosis factor-α for interleukin-10 production by
murine dendritic cells.
Hirata N, Yanagawa Y, Ogura H, Satoh M, Noguchi M, Matsumoto M,
Togashi H, Onoé K, Iwabuchi K.
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido
University, West 7 North 15, Sapporo 060-0815, Japan; Division of
Cancer Biology, Institute for Genetic Medicine, Hokkaido University,
West 7 North 15, Sapporo 060-0815, Japan.
Abstract
In the present study, we examined the role of tumor necrosis factor
(TNF) in interleukin (IL)-10 production by dendritic cells (DCs) using
bone-marrow derived DCs from wild type (WT) and TNF-α knockout (TNF-
α(-/-)) mice. Toll-like receptor (TLR) stimulation induced substantial
level of IL-10 production by WT DCs, but significantly low level of
IL-10 production by TNF-α(-/-) DCs. In contrast, no significant
difference was detected in IL-12 p40 production between WT and TNF-
α(-/-) DCs. Addition of TNF-α during TLR stimulation recovered the
impaired ability of TNF-α(-/-) DCs for IL-10 production. This recovery
appeared to be associated with an activation of extracellular signal-
regulated kinase, p38 mitogen-activated protein kinase, and
phosphatidylinositol 3-kinase/Akt following the TNF-α addition.
Blocking these kinases significantly inhibited IL-10 production by TNF-
α(-/-) DCs stimulated with TLR ligands plus TNF-α. Thus, TNF-α may be
a key molecule to regulate the balance between anti-inflammatory
versus inflammatory cytokine production in DCs.
PMID: 20979991
Phosphatidylinositol 3 kinase Akt looks familiar to the P NG
(psoriasis newsgroup btw is P NG).
What? ONLY 3 in the p ng?
3 results for phosphatidylinositol 3-kinase Akt - P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=phosphatidylinositol+3-kinase+Akt+&qt_g=Search+this+group
This is weird. I get more on ALL GROUPs and their MINE. LOL
Something is wrong with searching just OUR psor GROUP at times?
Oh well, it is what it is and we can always add a keyword and go up a
level and search ALL
groups. Which btw is exactly what i do anyway. LOL
psoriasis phosphatidylinositol 3 kinase Akt randall - 26 hits ALL
groups
http://groups.google.com/groups/search?hl=en&q=psoriasis+phosphatidylinositol+3+kinase+Akt+randall&sitesearch=
Same search all groups and no randall?
OK...
72 hits -psoriasis phosphatidylinositol 3 kinase Akt
http://groups.google.com/groups/search?hl=en&q=psoriasis+phosphatidylinositol+3+kinase+Akt+&sitesearch=
The PI3K/AKT signalling pathway - youtube
http://www.youtube.com/watch?v=ewgLd9N3s-4
keywords: ras pip3 akt bax p13k s6k rib mTOR foxo proteasome
cAMP signaling youtube <this is germane from the excess cGMP side>
http://www.youtube.com/watch?v=iGb93jCKVXs
46 hits for same search but replacing psoriasis with crohn's
crohn's phosphatidylinositol 3 kinase Akt
http://groups.google.com/groups/search?hl=en&q=crohn%27s+phosphatidylinositol+3+kinase+Akt&sitesearch=
86 results for p38 mitogen activated protein kinase
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=p38+mitogen+activated+protein+kinase&qt_g=Search+this+group
AT this point inhibiting p38 mitogen activated protein kinase sounds
like a good idea?
But really? Why not simply lower LPS by taking away the leaky AREA in
the Gi tract?
Certainly a better strategy and tells mister big PHARMA thanks BUT NO
THANKX, i'm going to causation and not going
the route of treating ulcers but curing them.
Same for us in my opinion.
Why not clear SFB and take away one of the legs of the STOOL? LOL
Clever. <G> <W>
OK find map p38 and LPS if your so clever and prove it.
Duh.. ok.
http://en.wikipedia.org/wiki/P38_mitogen-activated_protein_kinases
[...] p38 MAP kinase is activated by a variety of cellular stresses
including osmotic shock, inflammatory cytokines, lipopolysaccharides
(LPS), Ultraviolet light and growth factors.
<snip>
So why do we have extra or excess P38 mapk in the first place?
**MAPK/p38 inhibition can promote Th1 immune responses** <see next
abstract>
Why does p38 mapk tilt the skew to Th1?
I want enhanced stability of p40 IL-12?
RIGHTy OH!
http://www.ncbi.nlm.nih.gov/pubmed/20937847
J Immunol. 2010 Oct 11.
The Regulation of Th1 Responses by the p38 MAPK.
Yang Z, Zhang X, Darrah PA, Mosser DM.
Department of Cell Biology and Molecular Genetics and.
Abstract
IL-12 is a dimeric cytokine that is produced primarily by APCs. In
this study we examined the role that the p38 MAPKs (MAPK/p38) play in
regulating IL-12 production. We show that inhibition of p38
dramatically increased IL-12 production upon stimulation, while
decreasing TNF-α. This reciprocal effect on these two cytokines
following MAPK/p38 inhibition occurred in many different APCs,
following a variety of different stimuli. IL-12 production was also
increased in macrophages treated with small interfering RNA to limit
p38α expression, and in macrophages deficient in MKK3, a kinase
upstream of p38. The increase in IL-12 production following MAPK/p38
inhibition appears to be due to enhanced IL-12 (p40) mRNA stability.
We show that MAPK/p38 inhibition can promote Th1 immune responses and
thereby enhance vaccine efficacy against leishmaniasis. In a mouse
model of Leishmania major infection, vaccination with heat-killed L.
major plus CpG and SB203580 elicited complete protection against
infection compared with heat-killed L. major plus CpG without
SB203580. Thus, this work suggests that MAPK/p38 inhibitors may be
applied as adjuvants to bias immune responses and improve vaccinations
against intracellular pathogens.
PMID: 20937847
http://www.ncbi.nlm.nih.gov/pubmed/19897961
Targeted therapies in inflammatory bowel disease.
[...] pmid # 19897961
This one posted recently to the P NG:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=PMID%3A+19897961+&start=0&scoring=d&hl=en&
or
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/2301dd156f43e805
Mon, Oct 4 2010 12:54 pm
Subject: 2% of HANs on Psor DECK - STRESS - Indigo Herb - Candida on
P40 KO mice -IBD & P40 - Mercola - P60 binds FoxP3 with TREGs being
skewed - Selenium -
<sniP>
D3 induces Treg's?
It says so:
http://www.ncbi.nlm.nih.gov/pubmed/20930170
Oral Administration of an Active Form of Vitamin D3 (Calcitriol)
Decreases Atherosclerosis in Mice by Inducing Regulatory T Cells and
Immature Dendritic Cells With Tolerogenic Functions.
[...] PMID: 20930170
>
> > You gentlemen are forgetting that self-tolerance and innate immunity
> > appear to be the same thing. TLR4 is necessary for both innate defense
> > against pathogens and self-tolerance. When NOD2 damages the innate
> > response to bacteria it's also damaging an important part of the
> > complement cascade (coordinated via sympathetics) that defends self
> > tissue via IL-10...
>
> If the "majic herb" simultaneously suppresses p40 & pathogens, then it
> should be OK, right? According to pubmed thse include resveratrol,
> butyrate, azithromycin, PPARa,d,g agonists (ie curcumin, ASA), etc.
>
> And the following suppress Th/IL-17: apigenin, berberine, EGCG, GSE,
> herbal formula 'Huo luo xiao ling dan', bifidobacterium, retinoic
> acid, statins, D3, etc.
I don't recall this one.
'Huo luo xiao ling dan'
LOOKs good for PsA...
Does it help crohn's?
Cleans the blood?
The Tradional Chinese Medicine says fire in the kidneys for psoriasis.
Are they ON fire due to dirty blood?
Does that mean it's full of LPS (endotoxins)?
Does the RAP fall on the liver then?
http://www.ncbi.nlm.nih.gov/pubmed/19100323
J Ethnopharmacol. 2009 Jan 30;121(3):366-71. Epub 2008 Nov 28.
Extract of the Chinese herbal formula Huo Luo Xiao Ling Dan inhibited
adjuvant arthritis in rats.
Zhang RX, Fan AY, Zhou AN, Moudgil KD, Ma ZZ, Lee DY, Fong HH, Berman
BM, Lao L.
Center for Integrative Medicine, School of Medicine, University of
Maryland, 3rd Floor, James Kernan Hospital Man., 2200 Kernan Drive,
Baltimore, MD 21207, USA.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The herbal formula Huo Luo Xiao Ling
Dan (HLXL) and its modifications have been used in traditional Chinese
medicine for about one hundred years to alleviate pain and
inflammation.
AIM: To investigate the effects of HLXL on complete Freund's adjuvant
(CFA)-induced multiple-joint arthritis in rats.
MATERIALS AND METHODS: Male Lewis rats, 190-210 g, were immunized
subcutaneously at the base of the tail with 200 microl of heat-killed
Mycobacterium tuberculosis in mineral oil (5 mg/ml). HLXL (2.30 and
4.60 g/kg) or vehicle control (n=8 per group) was administered orally
(i.g.) once a day between days 16 and 25 post-CFA injection. The rats
were observed for signs of arthritis with arthritic changes (erythema,
edema, induration) being scored on a scale of 0-4 of increasing
severity using a standard scoring system. The maximum arthritis score
per rat was 16. A plethysmometer was used to measure edema volume in
each paw. Adverse effects of HLXL were monitored by closely observing
the animals for unusual behavioral changes. Levels of tumor necrosis
factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in local
tissue were measured by enzyme-linked immunosorbent assay on day 25
post-CFA.
RESULTS: HLXL significantly decreased arthritis scores between days
23-25 in the 2.30 g/kg group and 21-25 in the 4.60 g/kg group
(p<0.05). It reduced paw edema on days 22 and 24 in the 2.30 g/kg
group and on days 20, 22 and 24 in the 4.60 g/kg group compared to
control (p<0.05). Local tissue TNF-alpha and IL-1beta levels on day 25
post-CFA injection were significantly (p<0.05) lower in rats treated
with HLXL than in control rats. No observable adverse effects were
found.
CONCLUSION: The data suggest that HLXL produces significant anti-
arthritic effects that may be mediated by suppressing pro-inflammatory
cytokines, and it appears to be safe.
PMID: 19100323
Oh well... my magic herb is still working on kimchi...
But it's a food.
Can i prepare some of the other food turbo's with it?
I'll FIND out.
randall... the raP today is COME to=gether right NOW over ME? Meism
is psor, dude...OK sorry. LOL
Kofi
Rougly $3.8 billion - well above any election ever before and most of it
off the books.
Republicans outspent Democrats 8x to 10x and only finished a few percent
ahead in about 10% of House races (and I thought Republicans were
against subsidizing inefficient, unpopular enterprises).
>
>
> OK ok i'm calming DOWN.
>
> WE've got divided gov today.
Great. We're on the edge of a deflationary precipice like Japan in the
1990s and we've got a completely paralyzed government with the courts
and the House run by a party whose one stated priority is to see the
President fail. Patriotism first, right?
>
> Moo, moo, i'm gonna MILK that COW right outa my HAIR.
>
> And what's wrong with BUSHbabies, baby?
>
> http://www.youtube.com/watch?v=GN8fs5gn 38&feature=fvw
>
>
> And those commercials that demonize the demons of freedumb that
> drove me ad nauseum are DONE.
>
> Yea...
>
> But it still goes on?
>
> Phase II blame game continues?
>
>
> And like Clinton, is Obama going back to the center?
Obama was always in the center - in fact, dumping the public health
insurance option put him on the right of the electorate. Some
independents went to the polls yesterday and picked Republicans because
they wanted the parties to work together. WTF?! The Republicans just
spent the last two years filibustering everything. Democrats crafted
policies with broad popularity when you looked at the polls - extending
unemployment benefits (which Republicans periodically blocked), cap &
trade, reregulating Wall Street (which hardly any Republican supported),
mandating insurance companies stop descriminating against sick patients
and spend at least 80% of premiums on actual health care. There wasn't
really one major part of any law Obama signed that the electorate wanted
repealed. When you told them what was actually in the stimulus, they
wanted more of it - more roads, more tax cuts, more aid to strapped
state governments. Fox just managed to con Americans into conflating
the stimulus with TARP (which we made a profit on) with Wall Street
bonuses. Governors like Rick Perry took the stimulus funds to bridge
the state budget gap while denouncing it. It's kind of hard to run
against a party of unified liars who have ten times the money you do and
own a television network.
Obama's problem is that after he rescued the richest, most arrogant
crooks in the country's history instead of prosecuting them, he just
assumed they would be grateful. Sociopaths, narcissists and psychopaths
don't work that way. They have a deep and abiding sense of malignant
entitelment. They got steaming mad that he tried to reform the bad
business practices that were bringing them easy money and destroying the
economy - like the practice of putting holes ten thousand feet down in
the Gulf of Mexico without a plan for stopping them up or dropping the
policies of women who get breast cancer or forcing banks to adopt good
accounting practices. The Supreme Court deliberately misinterpreted the
constitution to give corporations unchecked ability to buy politicians
(read Federalist #10 if you want to see what the Founding Fathers
thought about organized financial interest). Now the system is so
corrupt, we don't even know how much of the TARP funds AIG and big banks
took and dropped on the Republicans who refused to vote for TARP in the
first place. Big business today is suicidally stupid.
You have a chronic illness and you're attacking the only party in
American history to pass a law preventing insurance companies from
defrauding you.
That's some gratitude you've got.
You're supporting Sarah Palin's point of view? The woman stood up and
said that giving health insurance to victims of terrorism, violent
crime, medical malpractice and just plain bad luck would set up
Nazi-style death camps that would execute old people.
"Thou shalt not lie."
I guess she just forgot that commandment.
I will never forget who sided with me.
jay
>>
>> Salicylanilides: selective inhibitors of interleukin-12p40
>
> I've found that aspirin will increase the leaky gut thingy.
> And add to inflammation in the long run.
> Even at a 62.5 mg baby aspirin dosage.
Does aspirin or it's derivatives (ie ASAs) work similar to PTPN22
(encodes a lymphoid-specific phosphatase (LYP), a down regulator of T-
cell activation, etc)? Above and below abstracts have me wondering. If
so, it could compensate for the PTPN22 1858C-T (R620W) variant. The
immune system may reduce it's response by the presence of natural anti-
pathogens (ie salicylates found in bark, etc).
A functional variant of lymphoid tyrosine phosphatase is associated
with type I diabetes.
We report that a single-nucleotide polymorphism (SNP) in the gene
(PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a
suppressor of T-cell activation, is associated with type 1 diabetes
mellitus (T1D). The variants encoded by the two alleles, 1858C and
1858T, differ in a crucial amino acid residue involved in association
of LYP with the negative regulatory kinase Csk. Unlike the more common
allele 1858C, the variant associated with T1D does not bind Csk. PMID:
15004560
Discovery of a novel submicromolar inhibitor of the lymphoid specific
tyrosine phosphatase.
We report here a class of thiazolidine-2,4-diones and 2-
thioxothiazolidin-4-ones as potent inhibitors of the lymphoid specific
tyrosine phosphatase (Lyp) identified from high throughput screens.
Chemical modification by incorporating the known phosphotyrosine
(pTyr) mimics led to the discovery of a salicylate-based inhibitor
with submicromolar potency. PMID: 18434147
Decreased IL-12 production and Th1 cell development by acetyl
salicylic acid-mediated inhibition of NF-kappaB.
IL-12 is a 75-kDa heterodimeric cytokine composed of two covalently
linked p35 and p40 chains. This pro-inflammatory cytokine plays a
prominent role in the development of Th1 cell-mediated immune
responses. Th1 cell-mediated immune responses have been implicated in
the pathogenesis of chronic inflammatory autoimmune diseases. Thus,
IL-12 appears to be a critical factor in the generation and
maintenance of chronic inflammatory conditions. In this study, we
investigated the effects of a commonly prescribed anti-inflammatory
drug, acetyl salicylic acid (ASA), on IL-12 production and Th1 cell
development. ASA was found to inhibit secretion of the IL-12
heterodimer as well as p40 monomer by human monocytic cells. This was
associated with the down-regulation of IL-12p40 mRNA expression.
Analysis of the regulation of the p40 gene promoter revealed that ASA
inhibited NF-kappaB activation and binding to the p40-kappaB site in
the p40 promoter, leading to transcriptional repression of the p40
gene. Addition of ASA to an in vitro T helper cell differentiation
system, at concentrations compatible with plasma levels reached during
anti-inflammatory therapy, resulted in reduced development of Th1
cells. These results suggest that the inhibition of NF-kappaB
activation by ASA leads to down-regulation of IL-12 production and
inhibition of Th1 cell development. PMID: 9808189
Salicylic acid in the serum of subjects not taking aspirin. Comparison
of salicylic acid concentrations in the serum of vegetarians, non-
vegetarians, and patients taking low dose aspirin
Abstract: Aims—To determine serum salicylic acid concentrations in non-
vegetarians and vegetarians not taking salicylate drugs, and to
compare these concentrations with those found in patients taking
aspirin, 75 mg daily.
Methods—Serum samples were obtained from vegetarians (n = 37) and non-
vegetarians (n = 39) not taking salicylate drugs. Non-vegetarians and
vegetarians were recruited from the community and from a Buddhist
monastery, respectively, in Dumfries and Galloway, Scotland. Patients
(n = 14) taking aspirin (75 mg daily) were recruited from the Dumfries
diabetic clinic. Serum salicylic acid concentrations were determined
using a high performance liquid chromatography method with
electrochemical detection.
Results—Salicylic acid was detected in every serum sample analysed.
Higher serum concentrations of salicylic acid were found in
vegetarians than non-vegetarians: median concentrations of 0.11
(range, 0.04–2.47) μmol/litre and 0.07 (range, 0.02–0.20) μmol/litre,
respectively; the median of the difference was 0.05 μmol/litre (95%
confidence interval for difference, 0.03 to 0.08; p < 0.0001). The
median serum concentration of salicylic acid in patients taking
aspirin (75 mg daily) was 10.03 (range, 0.23–25.40) μmol/litre, which
was significantly higher than that found in non-vegetarians and
vegetarians. There was overlap in serum salicylic acid concentrations
between the vegetarians and patients taking aspirin.
Conclusions—Salicylic acid, a non-steroidal anti-inflammatory drug, is
present in fruits and vegetables and is found in higher concentrations
in vegetarians than non-vegetarians. This suggests that a diet rich in
fruits and vegetables contributes to the presence of salicylic acid in
vivo. There is overlap between the serum concentrations of salicylic
acid in vegetarians and patients taking aspirin, 75 mg daily. These
findings may explain, in part, the health promoting effects of dietary
fruits and vegetables
Cyclooxygenase activity is increased in platelets from psoriatic
patients.
The aim of the present study was to ascertain the relationship between
in vitro hyper-aggregability and alterations in arachidonic acid
metabolism in platelets from psoriatic patients. We have studied the
response to several concentrations of ADP, collagen, and arachidonic
acid of intact platelets from psoriatic patients and normal subjects,
with and without irreversible inhibition of platelet cyclooxygenase by
aspirin. Apparent kinetic constants (apparent Michaelis constant [Km]
and apparent maximum velocity [Vmax]) of cyclooxygenase in platelets
from both controls and psoriatic patients were also studied. The
maximum percentage and slope of aggregation induced by collagen or
sodium arachidonate were significantly greater (p less than 0.05) in
platelets from psoriasis patients, whereas lag time was significantly
shorter in the psoriasis group in response to arachidonic acid only
when compared to controls. Cyclooxygenase pathway blockade inhibited
the response to aggregation inducers in the following order: sodium
arachidonate greater than collagen greater than ADP. When platelets
were pre-treated with aspirin no significant differences were observed
between controls and psoriasis patients. We also found a significant
increase of the apparent Vmax value (p less than 0.05) for
cyclooxygenase activity in platelets from psoriatic patients in
comparison with controls. Our results indicate that platelet
hyperaggregation in psoriatic patients is related to enhanced
cyclooxygenase activity in their platelets. PMID: 1919056
Aspirin reduces serum anti-melanocyte antibodies and soluble
interleukin-2 receptors in vitiligo patients.
OBJECTIVE: Increased serum levels of certain immunologic markers
including immunoglobulin G (IgG) anti-melanocyte/ vitiligo antibodies
(V-IgG) and soluble interleukin-2 receptors (sIL-2R) are associated
with augmented humoral and cellular immunity involved in melanocyte
cytotoxicity during the active phase of non-segmental vitiligo. Recent
reports have shown that, aspirin possesses a wide range of
immunomodulatory and antioxidant properties. Therefore, the aim of the
present study is to investigate the effect of long-term treatment of
vitiligo patients with low-dose oral aspirin on serum V-IgG activity
and sIL-2R concentration.
METHODS: The present study was carried out at the Vitiligo Unit, King
Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia
between March and October 2003. Eighteen female and 14 male patients
with a recent onset of non-segmental vitiligo were divided into 2
equal groups. One group received a daily single dose of oral aspirin
(300 mg) and the second group received only placebo for a period of 12
weeks. Serum V-IgG activity and sIL-2R concentration were determined
before and at the end of treatment period. The V-IgG activity was
measured using cellular enzyme-linked immunosorbent assay (ELISA)
following incubation of IgG antibodies with an adult cultured
melanocytes. Serum sIL-2R concentration was measured using the highly
sensitive quantitative sandwich ELISA utilizing a commercially
available kit.
RESULTS: As expected, the serum V-IgG activity and sIL-2R
concentration of the active vitiligo patients (0.81 +/- 0.23 optical
density (O.D.), 1428 +/- 510 pg/ml) were significantly increased
compared with that of controls (0.27 +/- 0.1 O.D., 846 +/- 312 pg/ml;
p<0.05, p<0.01). Aspirin-treated vitiligo patients showed significant
decrease in serum V-IgG activity and sIL-2R concentration (0.32 +/-
0.08 O.D., 756 +/- 216 pg/ml) compared with that of placebo-treated
patients (0.83 +/- 0.19 O.D., 1327 +/- 392 pg/ml; p<0.01).
CONCLUSION: Low-dose oral aspirin treatment of active vitiligo
patients can cause significant reduction in the acute serum
immunologic markers of T cell activation, V-IgG activity and sIL-2R
concentration with concomitant arrest of disease activity.
PMID: 16047057
Decreased proinflammatory cytokine production by peripheral blood
mononuclear cells from vitiligo patients following aspirin treatment.
OBJECTIVE: Limited studies have shown that treatment of cells with
aspirin modulates their cytokine production. Consequently, the aim of
the present study is to investigate the pattern of important
proinflammatory cytokines production by stimulated peripheral blood
mononuclear cells (PBMC) from patients with active vitiligo following
long-term treatment with low-dose oral aspirin.
METHODS: The study was conducted at the Vitiligo Unit, King Abdul-Aziz
University Medical Center, Jeddah, Kingdom of Saudi Arabia between
March and October 2003. Thirty-two patients (18 females and 14 males)
with non-segmental vitiligo were divided into 2 equal groups, one
group received a daily single dose of oral aspirin (300 mg) and the
other group received placebo for a period of 12 weeks. The
concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumor
necrosis factor-alpha (TNF-alpha) were determined in the supernatant
of isolated cultured PMBC after being stimulated with bacterial
lipopolysaccharide (LPS), before the start of aspirin treatment and at
end of treatment period. Cytokine levels were measured using the
quantitative sandwich enzyme-linked immunosorbent assay (ELISA)
technique, utilizing commercially available kits.
RESULTS: The proinflammatory cytokine production by the PBMC of
patients with active vitiligo was significantly increased compared to
normal controls. Thus, the relative percentage increase in the
production of IL-1beta, IL-6, IL-8 and TNF-alpha was: 39.4%, 110.5%
(p<0.05), 91.5% (p<0.01), and 37% (p<0.05). At the end of treatment,
proinflammatory cytokine production in the aspirin-treated group of
active vitiligo patients was significantly decreased compared to the
placebo group. Thus, the relative percentage decrease in the
production of IL-1beta IL-6, IL-8 and TNF-alpha was: 42.5%, 45.2%
(p<0.05), 30.8% (p<0.01), and 50.6% (p<0.05). The vitiligo activity
was arrested in all aspirin-treated patients, while 2 patients
demonstrated significant repigmentation.
CONCLUSION: Chronic administration of low-dose oral aspirin can down-
regulate the PBMC proinflammatory cytokine production in active
vitiligo with concomitant arrest of disease activity. PMID: 15951873
ScienceDaily (July 18, 2003) — Adding to the long list of the benefits
of aspirin, researchers have found that it is responsible for reducing
toxic bacteria associated with serious infections. A study led by
Dartmouth Medical School describes how salicylic acid-produced when
the body breaks down aspirin-disrupts the bacteria's ability to adhere
to host tissue, reducing the threat of deadly infections.
The investigation, which appears in the July 15 issue of the Journal
of Clinical Investigation, focused on the bacterium Staphylococcus
aureus, and its role in infections in animal tissue. S. aureus is a
leading cause of serious systemic (often referred to as staph)
infections and abscesses.
"Our research shows that salicylic acid, a byproduct of aspirin,
impacted the stress system of the bacteria and reduced its ability to
cause infection," said lead author Dr. Ambrose Cheung, a professor of
microbiology and immunology at Dartmouth Medical School.
By disrupting this stress system, aspirin reduced the bacteria's
capacity to adhere to host tissue. In addition, the salicylic acid
disrupted the ability of S. aureus to produce toxins, which the
bacteria require to propagate and spread to other tissue. As a result,
the animals treated with aspirin have smaller abscesses and they have
fewer number of bacteria in the infection. Aspirin did not cure it,
notes Cheung, but it reduced the ability of the bacteria to cause
infection.
The S. aureus bacteria are also responsible for sepsis, a blood
poisoning disease that strikes 750,000 people in the US annually and
is the leading cause of death in America's non-coronary intensive care
units. Cases of sepsis are growing in number each year and are
becoming increasingly resistant to antibiotics, making aspirin a
possibly invaluable option for treatment.
"The fact that aspirin has been used for pain treatment, to reduce
mortality due to heart attacks, and can possibly reduce the risks of
infection is incredible," said Cheung. "We look forward to conducting
future tests with aspirin in conjunction with antibiotic therapy.
randall
> >>> LPS > TLR4 > APC/DC > IL23 (p19 & p40) > IL23R of TH17 > IL17
> >>> ... we need a majic herb that bind p40s ...
>
> >> Salicylanilides: selective inhibitors of interleukin-12p40
> >> production... PMID: 18715785
>
> > I've found that aspirin will increase the leaky gut thingy.
> > And add to inflammation in the long run.
> > Even at a 62.5 mg baby aspirin dosage.
>
> Does aspirin or it's derivatives (ie ASAs) work similar to PTPN22
> (encodes a lymphoid-specific phosphatase (LYP), a down regulator of T-
> cell activation, etc)? Above and below abstracts have me wondering. If
> so, it could compensate for the PTPN22 1858C-T (R620W) variant. The
> immune system may reduce it's response by the presence of natural anti-
> pathogens (ie salicylates found in bark, etc).
This one is from 2007. Is it up to date enough?
http://www.ncbi.nlm.nih.gov/pubmed/18056643
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19767-72. Epub 2007 Dec
3.
Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-
specific tyrosine phosphatase implicated in autoimmune diseases.
Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY.
Department of Biochemistry and Molecular Biology, Indiana University
School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202.
Abstract
The lymphoid-specific tyrosine phosphatase (Lyp) has generated
enormous interest because a single-nucleotide polymorphism in the gene
(PTPN22) encoding Lyp produces a gain-of-function mutant phosphatase
that is associated with several autoimmune diseases, including type I
diabetes, rheumatoid arthritis, Graves disease, and systemic lupus
erythematosus. Thus, Lyp represents a potential target for a broad
spectrum of autoimmune disorders. Unfortunately, no Lyp inhibitor has
been reported. In addition, little is known about the structure and
biochemical mechanism that directly regulates Lyp function. Here, we
report the identification of a bidentate salicylic acid-based Lyp
inhibitor I-C11 with excellent cellular efficacy. Structural and
mutational analyses indicate that the inhibitor binds both the active
site and a nearby peripheral site unique to Lyp, thereby furnishing a
solid foundation upon which inhibitors with therapeutic potency and
selectivity can be developed. Moreover, a comparison of the apo- and
inhibitor-bound Lyp structures reveals that the Lyp-specific region
S(35)TKYKADK(42), which harbors a PKC phosphorylation site, could
adopt either a loop or helical conformation. We show that Lyp is
phosphorylated exclusively at Ser-35 by PKC both in vitro and in vivo.
We provide evidence that the status of Ser-35 phosphorylation may
dictate the conformational state of the insert region and thus Lyp
substrate recognition. We demonstrate that Ser-35 phosphorylation
impairs Lyp's ability to inactivate the Src family kinases and down-
regulate T cell receptor signaling. Our data establish a mechanism by
which PKC could attenuate the cellular function of Lyp, thereby
augmenting T cell activation.
PMID: 18056643 <------------------------<g>
I know, i know. but i like the above link to pubmed with the pmid #.
<w>
So if i get some nascent idea popping in my gray cells i can follow
willy nilly.
Must be a tyrosine thingy. LOL
But i'm not seeing crohn's or psor in the most recent of all ptpn22's
abstract.
http://www.ncbi.nlm.nih.gov/pubmed/21044313
BMC Mol Biol. 2010 Nov 2;11(1):78.
Identification of a variant form of tyrosine phosphatase LYP.
Wang S, Dong H, Han J, Ho WT, Fu X, Zhao ZJ.
Abstract
ABSTRACT:
BACKGROUND: Protein tyrosine phosphatases (PTPs) are important cell
signaling regulators with major pathological implications. LYP (also
known as PTPN22) is an intracellular enzyme initially found to be
predominately expressed in lymphocytes. Importantly, an allelic R620W
variant of LYP is strongly associated with multiple autoimmune
diseases, including systemic lupus erythematosus, rheumatoid
arthritis, type 1 diabetes, and autoimmune thyroid disease.
RESULTS: In this study, we isolated a novel isoform of LYP designated
LYP3. LYP3 differs from LYP1, the known isoform of LYP, in that it
lacks a 28 amino acid segment right after the R620W site embedded in a
proline-rich protein-protein interaction motif. Genomic sequence
analysis revealed that LYP3 resulted from alternative splicing of the
LYP gene located on chromosome 1p 13.3-13.1. Reverse transcription PCR
analyses of 48 human tissues demonstrated that both LYP1 and LYP3 are
predominantly expressed in primary and secondary lymphoid tissues but
the relative expression levels of the two isoforms varies in different
human tissues and individuals.
CONCLUSIONS: We thus identified a new variant form of LYP and
conducted a comprehensive analysis of LYP tissue expressions.
Considering the pathogenesis of LYP R620W, we believe that the
expression of LYP3 may have an important role in regulating activity
and function of LYP and may be implicated in autoimmune diseases.
PMID: 21044313
So your variant or mine does it make us LIBERAL like the drd4 gene
does? LOL
Jay can you check these out and let me know what you find?
18 hits - ptpn22 AND crohn's - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=ptpn22+crohn's
441 hits for ptpn22 - pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=ptpn22
About the same thing for psoria* AND ptpn22 - 14 hits
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=ptpn22+psoria*
But one day it's in and the next taken off the radar
Genet Test Mol Biomarkers. 2010 Feb;14(1):107-11.
http://www.ncbi.nlm.nih.gov/pubmed/20039785
The protein tyrosine phosphatase, non-receptor type 22 R620W
polymorphism does not confer susceptibility to psoriasis in the
genetic homogeneous population of Crete.
pmid # 20039785
On google news i see the same thing.
In or OUT?
Toss a DART from ONE day to the next, if ptpn22 is good or evil?
Still wondering now about tyrosine.
[...] The major histocompatibility complex class II transactivator
(CIITA) regulates MHC class II gene expression. A promoter SNP -168A/G
(rs3087456) has previously been shown to be associated with
susceptibility to several immune mediated disorders, including
rheumatoid arthritis (RA), multiple sclerosis (MS) and myocardial
infarction(MI).
[...] Conclusions: We thus conclude that previous findings with regard
to the role of the CIITA -168A/G SNP in autoimmunity may have to be
reconsidered.
OH WAIT... ptpn22 is back in?
[...] Protein tyrosine phosphatases (PTPs) are important cell
signaling regulators with major pathological implications. LYP (also
known as PTPN22) is an intracellular enzyme initially found to be
predominately expressed in lymphocytes.
Importantly, an allelic R620W variant of LYP is strongly associated
with multiple autoimmune diseases,
[...] Conclusions: We thus identified a new variant form of LYP and
conducted a comprehensive analysis of LYP tissue expressions.
Considering the pathogenesis of LYP R620W, we believe that the
expression of LYP3 may have an important role in regulating activity
and function of LYP and may be implicated in autoimmune diseases.
<snip>
Is tyrosine broken?
I don't think so.
http://en.wikipedia.org/wiki/PTPN22#Disease_association
The common 1858T (rs2476601) nonsynonymous single nucleotide
polymorphism located in the PTPN22 gene has been associated with a
range of autoimmune disorders, including Type 1 Diabetes, rheumatoid
arthritis, Systemic Lupus Erythematosus and Graves' disease
What exactly hapPens with autoimmunity and ptpn22?
252 hits - ptpn22 AND autoimmun* - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=ptpn22+autoimmun*
Lets go backweirds to tyrosine and ptpn22
But first i'll try this
tyrosine Salicyl* - 338 hits - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=tyrosine+Salicyl*
In the very first one we see the ability to bind EGFR's.
A good thing.
http://www.ncbi.nlm.nih.gov/pubmed/20583855
J Enzyme Inhib Med Chem. 2010 Jun 28.
Synthesis and antiproliferative activities against Hep-G2 of
salicylanide derivatives: potent inhibitors of the epidermal growth
factor receptor (EGFR) tyrosine kinase.
Zhu ZW, Shi L, Ruan XM, Yang Y, Li HQ, Xu SP, Zhu HL.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing
University, Nanjing 210093, People's Republic of China.
Abstract
A series of salicylanilide derivatives (compounds 1-32) were
synthesised by reacting substituted salicylic acids and anilines. The
chemical structures of these compounds were determined by (1)H-NMR,
electrospray ionisation mass spectrometry (ESI-MS) and elemental
analysis. The compounds were assayed for their antiproliferative
activities against the Hep-G2 cell line by the 3-(4,5-
dimethylthylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
method. Among the compounds tested, 22 and 28 showed the most
favouable antiproliferative activities with 50% inhibitory
concentration (IC(50)) values of 1.7 and 1.3 muM, respectively, which
were comparable to the positive control of 5-fluorouracil (IC(50) =
1.8 muM). A solid-phase ELISA assay was also performed to evaluate the
ability of compounds 1-32 to inhibit the autophosphorylation of the
epidermal growth factor receptor tyrosine kinase (EGFR TK). Docking
simulations of 22 and 28 were carried out to illustrate the binding
mode of the molecule into the EGFR active site, and the result
suggested that both compounds 22 and 28 could bind the EGFR kinase
well.
PMID: 20583855
How much tyrosine do we NEED and is it broken?
I can't imagine it.
But that question is stuck in my MIND now.
Like trying to figue out how well conserved the gene may be?
Is that even aplicable?
I'll look next.
292 results for tyrosine - P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=tyrosine
So i need to read some of these as WELL.
And when i re-read this take my aspirin. LOL
randall... going ptpn22 OMIM instead? Surely...
jay
> in the most recent of all ptpn22's abstract.
World J Gastroenterol. 2010 Jan 28
Lymphoid tyrosine phosphatase R620W variant and inflammatory bowel
disease in Tunisia.
AIM: To assess the possible association between PTPN22 (R620W) gene
polymorphism and inflammatory bowel disease (IBD).
METHODS: One hundred and sixty-four patients with IBD [105 Crohn's
disease (CD) and 59 ulcerative colitis (UC)] and 100 healthy controls
were recruited. Genotyping of the PTPN22 gene 1858C-->T polymorphism
was performed by restriction fragment length polymorphism-polymerase
chain reaction with RsaI digestion.
RESULTS: The genotypic and allelic frequencies of (R620W) PTPN22 gene
polymorphism reveal a significant association of the PTPN22 620-W
allele with IBD, compared to the healthy control group (OR: 17.81, 95%
CI: 4.18-21.86, P = 0.00001). Nevertheless, no difference in this
polymorphism was found between CD and UC patients. No significant
association was found between the frequencies of genotypes of the
PTPN22 gene with either the clinical features such as sex, age, age at
disease onset, and extent of colitis, or the production of serological
markers (anti-Saccharomyces cerevisiae antibody in CD and perinuclear
anti-neutrophil cytoplasmic antibody in UC).
CONCLUSION: These observations confirm the association of IBD
susceptibility with the PTPN22 1858T (620-W) allele in Tunisian
patients. PMID: 20101775
jay
> abstract.
J Invest Dermatol. 2009 Mar
Further genetic evidence for three psoriasis-risk genes: ADAM33,
CDKAL1, and PTPN22.
Predisposition to psoriasis is known to be affected by genetic
variation in HLA-C, IL12B, and IL23R, and although other psoriasis-
associated variants have been identified, incontrovertible statistical
evidence for these markers has not yet been obtained. To help resolve
this issue, we tested 15 single-nucleotide polymorphisms (SNPs) from 7
putative psoriasis-risk genes in 1,448 psoriasis patients and 1,385
control subjects; 3 SNPs, rs597980 in ADAM33, rs6908425 in CDKAL1 and
rs3789604 in PTPN22, were significant with the same risk allele as in
prior reports (one-sided P<0.05, false discovery rate<0.15). These
three markers were tested in a fourth sample set (599 cases and 299
controls); one marker, rs597980, replicated (one-sided P<0.05) and the
other two had odds ratios with the same directionality as in the
original sample sets. Mantel-Haenszel meta-analyses of all available
case-control data, including those published by other groups, showed
that these three markers were highly significant (rs597980: P=0.0057
(2,025 cases and 1,597 controls), rs6908425: P=1.57 x 10(-5) (3,206
cases and 4,529 controls), and rs3789604: P=3.45 x 10(-5) (2,823 cases
and 4,066 controls)). These data increase the likelihood that ADAM33,
CDKAL1, and PTPN22 are true psoriasis-risk genes. PMID: 18923449
jay
> > (encodes a lymphoid-specific phosphatase (LYP), a down regulator of T-
> >
> > Discovery of a novel submicromolar inhibitor of the lymphoid specific
> > tyrosine phosphatase.
> > We report here a class of thiazolidine-2,4-diones and 2-
> > thioxothiazolidin-4-ones as potent inhibitors of the lymphoid specific
> > tyrosine phosphatase (Lyp) identified from high throughput screens.
> > Chemical modification by incorporating the known phosphotyrosine
> > (pTyr) mimics led to the discovery of a salicylate-based inhibitor
> > with submicromolar potency. PMID: 18434147
Dagnabbit. The LYP inhibitor above does exactly opposite of what a
person with PTPN22 C1858T would want, that is to down regulate T/B-
cell activation. Since the variant LYP doesn't work, need a substitute
that could can instead bind with LCK, Fyn, Zap-70 and especially Csk
at it's SH3. Seems unlikely :(
> Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-
> specific tyrosine phosphatase implicated in autoimmune diseases.
> ...Our data establish a mechanism by
> which PKC could attenuate the cellular function of Lyp, thereby
> augmenting T cell activation. PMID: 18056643
Won't people with AI diseases will need the opposite? Something that
augments function of LYP to down regulate T-cell activation.
> Synthesis and antiproliferative activities against Hep-G2 of
> salicylanide derivatives: potent inhibitors of the epidermal growth
> factor receptor (EGFR) tyrosine kinase.
> A series of salicylanilide derivatives (compounds 1-32) were
> synthesised by reacting substituted salicylic acids and anilines.
> ...result suggested that both compounds 22 and 28
> could bind the EGFR kinase well. PMID: 20583855
Will the above salicylanilide derivatives affect CSK, LCK, FyN, Zap-70
which are targets of LYP?
The following salicylic derivative blocks T-cell activation via a
different method, by blocking NFAT (see
www.bio.davidson.edu/courses/Immunology/Students/spring2006/Acker/YFIP.html).
Could this benefit people with PTPN22 C1858T variants?
UR-1505, a new salicylate, blocks T cell activation through nuclear
factor of activated T cells.
2-Hydroxy-4(-2,2,3,3,3-pentafluoropropoxy)-benzoic acid (UR-1505), a
new molecule chemically related to salicylic acid, has immunomodulator
properties and is currently under clinical development for treatment
of atopic dermatitis. The present work describes the immunomodulatory
profile of UR-1505. UR-1505 targets T cells, inhibiting their
proliferation and cytokine production by blocking nuclear factor of
activated T cells (NF-AT) DNA-binding activity. The effects of UR-1505
(100-300 microM) on T cell proliferation seems to be dependent on the
stimulus, because UR-1505 inhibited CD3/CD28-induced T-cell
proliferation, increased p27(KIP) levels, and induced G1/S cell arrest
but, interestingly, did not inhibit the Janus tyrosine kinase/signal
transducer and activator of transcription-induced T-cell
proliferation. These data suggest that UR-1505 acts by means of a
specific mechanism inhibiting T cell activation depending on T cell
receptor signaling pathway. Furthermore, the antiproliferative effects
of UR-1505 are not a consequence of decreased cell viability. In
addition to the inhibition of T-cell proliferation, UR-1505 decreased,
in a dose-dependent manner, the production of interleukin (IL)-5 and
interferon (IFN)-gamma in activated T cells, and this effect was
produced at the transcriptional level. Because T-cell proliferation
and cytokine production were regulated through NF-AT, we examined the
effect of UR-1505 on this transcription factor. According to its
effect on IL-5 and IFN-gamma mRNA expression, UR-1505 specifically
inhibited NF-AT DNA binding without effect on nuclear factor-kappaB
and activator protein-1 activities. The effect of UR-1505 on NF-AT is
not attributable to a blockade of nuclear import. In conclusion,
UR-1505 is a new immunomodulator agent that specifically inhibits NF-
AT activation. Because NF-AT regulates the transcription of most genes
involved in lymphocyte activation, its selective inactivation results
in both decreased T-cell proliferation and cytokine production. PMID:
17475810
And see the following somewhat related abstract:
Lipopolysaccharide, high glucose and saturated fatty acids induce
endoplasmic reticulum stress in cultured primary human adipocytes:
Salicylate alleviates this stress.
Recent findings indicate that endoplasmic reticulum (ER) stress is
significantly increased in adipose tissue of obese human subjects and
is critical to the initiation and integration of pathways of
inflammation and insulin action. But the factors inducing ER stress in
human adipose tissue are unknown. The common factors increased in
obesity and linked to insulin resistance are hyperglycaemia,
hyperlipidemia and also endotoxemia. Therefore, our aims were to
investigate: (1) the role of lipopolysaccharide (LPS), high glucose
(HG) and saturated fatty acids (SFA) as inducers of ER stress in
primary human adipocytes and (2) whether salicylate, a known anti-
inflammatory compound, can alleviate this effect. Components of the ER
stress pathways were studied in human abdominal subcutaneous (AbSc)
adipose tissue (AT) from obese and lean. Following the culture and
differentiation of primary human preadipocytes, these adipocytes were
treated with LPS, HG, tunicamycin (Tun) and SFA either alone or in
combination with sodium salicylate (Sal). Markers of ER stress were
significantly increased in AbSc AT of obese. Differentiated human
adipocytes treated with LPS, Tun, HG and SFA showed significant
activation of eukaryotic translation initiation factor 2alpha
(eIF2alpha) and activating transcription factor 6 (ATF6) and their
down-stream targets. Sal alleviated this effect and activated
AktSer473 phosphorylation. This study presents important evidence
that: (1) there is increased ER stress in adipose tissue of obese
individuals, (2) LPS, hyperglycaemia and saturated fatty acids induce
significant ER stress in primary human adipocytes and (3) this
induction is alleviated by salicylate. PMID: 20515657
jay
>
> Dagnabbit. The LYP inhibitor above does exactly opposite of what a
> person with PTPN22 C1858T would want, that is to down regulate T/B-
> cell activation. Since the variant LYP doesn't work, need a substitute
> that could can instead bind with LCK, Fyn, Zap-70 and especially Csk
> at it's SH3. Seems unlikely :(
Bite my tongue! Of the things that LYP inhibits, LCK might be the most
important for down regulating T-cell activation. So a LCK inhibitor
might do quite well for PTPN C1858T
From Wiki:
Lck is most commonly found in T cells. It associates with the
cytoplasmic tails of the CD4 and CD8 co-receptors on T helper cells
and cytotoxic T cells, respectively, to assist signaling from the T
cell receptor (TCR) complex.
Nilotinib inhibits the Src-family kinase LCK and T-cell function in
vitro.
PMID: 19374687 2009 Mar
New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck.
A novel series of pyrazolo[1,5a]pyrimidines was optimized to target
lymphocyte-specific kinase (Lck). An efficient synthetic route was
developed and SAR studies toward activity and selectivity are
described, leading to Lck inhibitors with enzymatic, cellular and in
vivo potency.PMID: 20483608 2010 Jun
Ring-fused pyrazole derivatives as potent inhibitors of lymphocyte-
specific kinase (Lck):
We have identified a novel series of ring-fused pyrazole derivatives
as lymphocyte-specific kinase (Lck) inhibitors. The most potent
analogs exhibited good enzyme inhibitory activity (IC(50)s <1nM) as
well as excellent cellular activity against mixed lymphocyte reaction
(MLR) (IC(50)s <1nM). PMID: 19945867 2010 Jan
From Wikipedia:
Pyrazole refers both to the class of simple aromatic ring organic
compounds ... having pharmacological effects on humans, they are
classified as alkaloids, although they are rare in nature.[1] In 1959,
the first natural pyrazole, 1-pyrazolyl-alanine, was isolated from
seeds of watermelons.
In medicine, derivatives of pyrazoles are used for their analgesic,
anti-inflammatory, antipyretic, antiarrhythmic, tranquilizing, muscle
relaxing, psychoanaleptic, anticonvulsant, monoamineoxidase
inhibiting, antidiabetic and antibacterial activities.
Celecoxib, a pyrazole derivative used as an analgesic
Celecoxib is a sulfa non-steroidal anti-inflammatory drug (NSAID) used
in the treatment of osteoarthritis, rheumatoid arthritis, acute pain,
painful menstruation and menstrual symptoms, and to reduce numbers of
colon and rectum polyps in patients with familial adenomatous
polyposis. It is marketed by Pfizer. It is known under the brand name
Celebrex or Celebra for arthritis and Onsenal for polyps.
Hmm, since PTPN22 C1858T, linked with RA, makes LYP unable to bind csk
which normally binds LCK, it seems to make sense (to me) that a
Celebrex, a pyrazole derivative, could bind LCK thus reduce RA. Is
this how Celebrex works?
Insufficient deactivation of the protein tyrosine kinase lck amplifies
T-cell
In the vulnerable atherosclerotic plaque, T cells may destabilize the
tissue structure through direct cell-injurious effector functions. T
cells transmit environmental signals, such as recognition of antigen,
into cellular responses through regulated phosphorylation of
cytoplasmic proteins, with the Src family kinase Lck (lymphocyte-
specific protein tyrosine kinase) in critical membrane-proximal
position of the T-cell receptor (TCR) signaling cascade. The balance
between protein phosphorylation and dephosphorylation defines the
signal transduction threshold and determines appropriate T-cell
responses... An intrinsic abnormality in the signaling machinery of
ACS T cells resulting in the accumulation of active Lck lowers the TCR
threshold and renders lymphocytes hyperreactive and capable of
unwanted immune responses. PMID: 20035083 2010 Mar
Lck regulates IL-10 expression in memory-like Th1 cells.
The Src family kinase Lck is thought to facilitate Th2
differentiation; however, its role in Th1 cells has not been well
explored. Using mice that lack Lck in mature T cells, we find that
lck(-/-) Th1 skewed cells have normal expression of T-bet and produce
IFN-γ at WT levels. However, there is a 3-fold increase in IL-10
producing cells in the mutant cultures. These cells do not have
elevated levels of IL-4, GATA3, IL-17 or Foxp3, indicating that they
are not Th2, Th17, or Foxp3(+) T regulatory cells (Treg). Nor do these
cells behave in a similar manner as the type 1 Treg. Most of the IL-10
in the lck(-/-) Th1 cultures is derived from the memory/activated
subset, as the cytokine profile from Th1 cultures established from
purified CD62L(+) (naïve) cells are similar to WT cells. Furthermore,
this IL-10 expression appears to be dependent on IL-12 and correlates
with elevated c-Maf. These data highlight a previously unappreciated
role for Lck in regulating IL-10 in Th1 cells.PMID: 20979231 2010 Sep
Atorvastatin restores Lck expression and lipid raft-associated
signaling in T cells from patients with systemic lupus erythematosus.
Loss of tolerance to self-Ags in patients with systemic lupus
erythematosus (SLE), a prototypic autoimmune disease, is associated
with dysregulation of T cell signaling, including the depletion of
total levels of lymphocyte-specific protein kinase (Lck) from
sphingolipid-cholesterol-enriched membrane microdomains (lipid rafts).
Inhibitors of 3-hyroxy-3-methylgluteryl CoA reductase (statins) can
modify the composition of lipid rafts, resulting in alteration of T
cell signaling. In this study, we show that atorvastatin targets the
distribution of signaling molecules in T cells from SLE patients, by
disrupting the colocalization of total Lck and CD45 within lipid
rafts, leading to a reduction in the active form of Lck. Upon T cell
activation using anti-CD3/anti-CD28 in vitro, the rapid recruitment of
total Lck to the immunological synapse was inhibited by atorvastatin,
whereas ERK phosphorylation, which is decreased in SLE T cells, was
reconstituted. Furthermore, atorvastatin reduced the production of
IL-10 and IL-6 by T cells, implicated in the pathogenesis of SLE.
Thus, atorvastatin reversed many of the signaling defects
characteristic of SLE T cells. These findings demonstrate the
potential for atorvastatin to target lipid raft-associated signaling
abnormalities in autoreactive T cells and provide a rationale for its
use in therapy of autoimmune disease. PMID: 17082661 2006 Nov
Glucocorticoids cause rapid dissociation of a T-cell-receptor-
associated protein complex containing LCK and FYN.
Although glucocorticoid (GC)-induced nongenomic effects have been
reported, the underlying mechanisms remain unexplained. ... Short-term
GC treatment induces dissociation of this protein complex, resulting
in impaired TCR signalling as a consequence of abrogated LCK/FYN
activation... PMID: 16888650
Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation
of p56(Lck).
Lipoic acid is an antioxidant that suppresses and treats a model of
multiple sclerosis, experimental autoimmune encephalomyelitis. We now
demonstrate that treatment of human PBMC and T cell lines with LA
downmodulated CD4 expression in a concentration-dependent manner. LA
treatment of Con A stimulated PBMC specifically removed CD4 from the T-
cell surface, but not CD3. Epitope masking by LA was excluded by using
monoclonal antibodies targeting different domains of CD4. Incubation
on ice inhibited CD4 removal following LA treatment, suggesting that
endocytosis was involved in its downmodulation. LA is in a unique
category of compounds that induce CD4 downmodulation by various
mechanisms (e.g., gangliosides). We hypothesized that LA might induce
dissociation of p56(Lck) from CD4, thus leading to its downmodulation.
Immunoblot analyses demonstrated reduced co-precipitation of p56(Lck)
from Jurkat T-cells following LA treatment and precipitation of CD4.
This unique immunomodulatory effect of LA warrants further
investigation. PMID: 16631599 2006 Jun
QSAR study of p56(lck) protein tyrosine kinase inhibitory activity of
flavonoid derivatives using MLR and GA-PLS.
Quantitative relationships between molecular structure and p56(lck)
protein tyrosine kinase inhibitory activity of 50 flavonoid
derivatives are discovered by MLR and GA-PLS methods. Different QSAR
models revealed that substituent electronic descriptors (SED)
parameters have significant impact on protein tyrosine kinase
inhibitory activity of the compounds. Between the two statistical
methods employed, GA-PLS gave superior results. The resultant GA-PLS
model had a high statistical quality (R(2) = 0.74 and Q(2) = 0.61) for
predicting the activity of the inhibitors. The models proposed in the
present work are more useful in describing QSAR of flavonoid
derivatives as p56(lck) protein tyrosine kinase inhibitors than those
provided previously.
Rosmarinic acid inhibits TCR-induced T cell activation and
proliferation in an Lck-dependent manner.
Lck is a T cell-restricted Src family protein tyrosine kinase that
plays pivotal roles in TCR-mediated signaling. We aimed to identify
novel agents that could disrupt the molecular interaction of the Src
homology 2-domain of Lck (Lck SH2) with its binding partners, with the
expectation that this would impair TCR signaling and generate
immunosuppression. Large-scale screening of plant extracts indicated
that rosmarinic acid (RosA) in extracts of Prunella vulgaris
consistently inhibits the interaction between Lck SH2 and a peptide
containing its consensus binding sequence (pYEEI). The inhibitory
effect of RosA was specific for SH2 domains of Src family protein
tyrosine kinase. RosA inhibited TCR-induced-Ca(2+) mobilization and
IL-2 promoter activation but not phorbol 12-myristate 13-acetate/
ionomycin-induced IL-2 promoter activation, indicating its point of
inhibition at the membrane proximal site of TCR signaling.
Furthermore, RosA inhibited TCR-induced splenocyte proliferation as
well as one-way MLR at an IC(50) of 25-50 microM and inhibited
cytokine expression such as IL-2 and IFN-gamma. Here, we first report
RosA as an inhibitor of TCR-signaling and subsequent T cell
proliferation. PMID: 12672052
My grocery list for the weekend: aspirin, statins, cortisone,
celebrex, lipoic acid, flavonoids and rosemary :)
Kofi
inhibitors block macrophage inflammatory agonism via the LL-37/P2X7
pathway. Hence one mutation of PTPN22 that raises the risk for type I
diabetes and arthritis simultaneously protects against colitis. Colitis
is a loss-of-function problem in macrophages, remember? In this sense,
PTPN22 seems to be very similar to GM-CSF. Deficiency in GM-CSF
contributes to colitis whereas overabundance leads to the
overinflammation seen in arthritis.
P2X7 is regulated by cathelicidin (neurodegeneration involving decreased
ATP production by mitochondria would lower ATP activation of P2X7);;
Macrophages are unique innate immune cells that play an integral role in
the defense of the host by virtue of their ability to recognize, engulf,
and kill pathogens while sending out danger signals via cytokines to
recruit and activate inflammatory cells. It is becoming increasingly
clear that purinergic signaling events are essential components of the
macrophage response to pathogen challenges and disorders such as sepsis
may be, at least in part, regulated by these important sensors. The
activation of the P2X7 receptor is a powerful event in the regulation of
the caspase-1 inflammasome; inflammasome activation requires "priming"
of macrophages prior to ATP activation of the P2X7R. Inhibition of the
inflammasome activation by the tyrosine kinase inhibitor, AG126,
suggests regulation by phosphorylation. Finally, the P2X(7)R may also be
activated by other elements of the host response such as the
antimicrobial peptide LL-37, which adds a new, physiologically relevant
agonist to the P2X7R pathway. Therapeutic approaches to inflammation and
sepsis will certainly be enhanced by an increased understanding of how
purinergic receptors modulate the inflammasomes [PMID 19214778]
Inflammatory bowel disease, including Crohn's disease (CD) and
ulcerative colitis (UC), and type 1 diabetes (T1D) are autoimmune
diseases that may share common susceptibility pathways. We examined
known susceptibility loci for these diseases in a cohort of 1689 CD
cases, 777 UC cases, 989 T1D cases and 6197 shared control subjects of
European ancestry, who were genotyped by the Illumina HumanHap550 SNP
arrays. We identified multiple previously unreported or unconfirmed
disease associations, including known CD loci (ICOSLG and TNFSF15) and
T1D loci (TNFAIP3) that confer UC risk, known UC loci (HERC2 and IL26)
that confer T1D risk and known UC loci (IL10 and CCNY) that confer CD
risk. Additionally, we show that T1D risk alleles residing at the
PTPN22, IL27, IL18RAP and IL10 loci protect against CD. Furthermore, the
strongest risk alleles for T1D within the major histocompatibility
complex (MHC) confer strong protection against CD and UC; however, given
the multi-allelic nature of the MHC haplotypes, sequencing of the MHC
locus will be required to interpret this observation. These results
extend our current knowledge on genetic variants that predispose to
autoimmunity, and suggest that many loci involved in autoimmunity may be
under a balancing selection due to antagonistic pleiotropic effect. Our
analysis implies that variants with opposite effects on different
diseases may facilitate the maintenance of common susceptibility alleles
in human populations, making autoimmune diseases especially amenable to
genetic dissection by genome-wide association studies [PMID 20176734]
In article
<6a258976-2ae2-4bf2...@a9g2000pro.googlegroups.com>,
Kofi
They
- block gut repair processes (and bone repair and joint repair...)
- impair Tregs
- block PGD2, known to help in colitis
- impair macrophage inflammatory response (PGE2)
jay
> proliferation in an Lck-dependent manner.
> and subsequent T cell proliferation. PMID: 12672052
Per wiki:
Rosmarinic acid, is a polyphenol found in many Lamiaceae herbs (mint
family) used commonly as culinary herbs such as lemon balm, rosemary,
oregano, sage, thyme and peppermint.
Because of the antioxidant activity of Lamiaceaeous herbs in
laboratory test models they have been suggested to have beneficial
effects in humans. Rosmarinic acid has a number of interesting
biological activities, e.g. antiviral, antibacterial, anti-
inflammatory and antioxidant. The presence of rosmarinic acid in
medicinal plants, herbs and spices has beneficial and health promoting
effects. In plants, rosmarinic acid is supposed to act as a preformed
constitutively accumulated defense compound.
This next 2 abstracts are killers!
Rosmarinic acid induces p56lck-dependent apoptosis in Jurkat and
peripheral T cells via mitochondrial pathway independent from Fas/Fas
ligand interaction.
Apoptosis is one way of controlling immune responses, and a variety of
immunosuppressive drugs suppress harmful immune responses by inducing
apoptosis of lymphocytes. In this study we observed that rosmarinic
acid, a secondary metabolite of herbal plants, induced apoptosis in an
p56(lck) (Lck)-dependent manner; Lck(+) Jurkat T cells undergo
apoptosis in response to rosmarinic acid (RosA) treatment, whereas
Lck(-) Jurkat subclone J.CaM1.6 cells do not. J.CaM1.6 cells with
various Lck mutants indicated that Lck SH2 domain, but not Lck kinase
activity, was required for RosA-induced apoptosis. RosA induced
apoptosis in the absence of a TCR stimulus, and this was not prevented
by interruption of the Fas/Fas ligand interaction. Instead, RosA-
mediated apoptosis involved a mitochondrial pathway as indicated by
cytochrome c release and the complete blockage of apoptosis by an
inhibitor of mitochondrial membrane depolarization. Both caspase-3 and
-8 were indispensable in RosA-induced apoptosis and work downstream of
mitochondria and caspase-9 in the order of caspase-9/caspase-3/
caspase-8. In freshly isolated human PBMC, RosA specifically induced
apoptosis of Lck(+) subsets such as T and NK cells, but not Lck-
deficient cells, including B cells and monocytes. Moreover, RosA's
ability to kill T and NK cells was restricted to actively
proliferating cells, but not to resting cells. In conclusion, Lck-
dependent apoptotic activity may make RosA an attractive therapeutic
tool for the treatment of diseases in which T cell apoptosis is
beneficial. PMID: 14688312
Rosmarinic acid induces apoptosis of activated T cells from rheumatoid
arthritis patients via mitochondrial pathway.
T cells play an important role in the initiation and the progression
of rheumatoid arthritis (RA) and depletion of potentially pathogenic T
cells was suggested as an important therapeutic protocol. We
determined if rosmarinic acid (RosA), known as a secondary metabolite
from herbal plants, had apoptotic activity toward T cells from RA
patients and further verified target T-cell subsets. CD3(+)CD25(+)
activated T-cell subsets from most of the RA patients displayed
significantly higher apoptosis rates than did the PBMCs and total
CD3(+) T cells. Furthermore, activated and effector CD4(+) T cells,
including CD4(+)CD25(+) and CD4(+)CD45RO(+) T cells, had a tendency of
being more susceptible to RosA-induced apoptosis than that of resting
and naïve T-cell subsets. RosA induced the release of cytochrome c
from mitochondria and the blockage of mitochondrial depolarization
inhibited apoptosis. Taken together, these results suggest that RosA
induces apoptosis of activated T-cell subsets from RA patients via a
mitochondrial pathway. PMID: 17195044
Protection against LPS-induced cartilage inflammation and degradation
provided by a biological extract of Mentha spicata.
A variety of mint [Mentha spicata] has been bred which over-expresses
Rosmarinic acid (RA) by approximately 20-fold. RA has demonstrated
significant anti-inflammatory activity ... an effective inhibitor of
LPS-induced inflammation in cartilage explants ... PMID: 20459798
Rosmarinic acid in Prunella vulgaris ethanol extract inhibits
lipopolysaccharide-induced prostaglandin E2 and nitric oxide in RAW
264.7 mouse macrophages.
Prunella vulgaris has been used therapeutically for inflammation-
related conditions for centuries, but systematic studies of its anti-
inflammatory activity are lacking and no specific active components
have been identified. In this study, water and ethanol extracts of
four P. vulgaris accessions were applied to RAW 264.7 mouse
macrophages, and the ethanol extracts significantly inhibited
lipopolysaccharide (LPS)-stimulated prostaglandin E2 (PGE2) and nitric
oxide (NO) production at 30 microg/mL without affecting cell
viability. Extracts from different accessions of P. vulgaris were
screened for anti-inflammatory activity to identify accessions with
the greatest activity. The inhibition of PGE2 and NO production by
selected extracts was dose-dependent, with significant effects seen at
concentrations as low as 10 microg/mL. Fractionation of ethanol
extracts from the active accession, Ames 27664, suggested fractions 3
and 5 as possible major contributors to the overall activity.
Rosmarinic acid (RA) content in P. vulgaris was found to independently
inhibit inflammatory response, but it only partially explained the
extracts' activity. LPS-induced cyclooxygenase-2 (COX-2) and nitric
oxide synthase (iNOS) protein expression were both attenuated by P.
vulgaris ethanol extracts, whereas RA inhibited only COX-2 expression.
PMID: 19919113
Rosmarinic acid protects against experimental sepsis by inhibiting
proinflammatory factor release and ameliorating hemodynamics.
The present study was to investigate the effects of rosmarinic acid
(RA) in cultured RAW264.7 cells and experimental model of sepsis
induced by cecal ligation and puncture [OUCH!] in rats and the
potential mechanism. Results showed that RA concentration dependently
down-regulated the levels of TNF-alpha, IL-6, and high-mobility group
box 1 protein in LPS-induced RAW264.7 cells, inhibited the IkappaB
kinase pathway, and modulated nuclear factor-kappaB. Intravenous
injection of RA alone or in combination with imipenem reduced cecal
ligation and puncture-induced lethality in rats. In addition, serum
levels of TNF-alpha, IL-6, high-mobility group box 1 protein,
triggering receptor expressed on myeloid cells, and endotoxin were
down-regulated; in contrast, serum level of IL-10 was up-regulated.
Amelioration of hemodynamics and decrease in serum enzyme activities
and myeloperoxidase in lung, liver, and small intestine were also
observed after RA injection. These data indicate that the antisepsis
effect of RA was mediated by decreasing local and systemic levels of a
wide spectrum of inflammatory mediators. This article provides the
first evidence that RA has the capacity to inactivate inflammatory
response in sepsis. The anti-inflammatory mechanism of RA may inhibit
activation of the nuclear factor- kappaB pathway by inhibiting IkappaB
kinase activity. PMID: 19295475
Effect of rosmarinic acid on atopic dermatitis.
Rosmarinic acid is known to have anti-inflammatory and
immunomodulatory activities. This study was performed to evaluate the
effect of rosmarinic acid on atopic dermatitis (AD), one of the
inflammatory disorders of the skin. ... AD-mitigating effect of
rosmarinic acid through in vivo experiments demonstrated the possible
clinical use of rosmarinic acid as a therapeutic agent for AD. PMID:
19239556
Prunella vulgaris extract and rosmarinic acid suppress
lipopolysaccharide-induced alteration in human gingival fibroblasts.
Periodontitis is a chronic disease associated with inflammation of the
tooth-supporting tissues. The inflammation is initiated by a group of
gram-negative anaerobic bacteria. These express a number of irritating
factors including a lipopolysaccharide (LPS), which plays a key role
in periodontal disease development. Plant extracts with anti-
inflammatory and anti-microbial properties have been shown to inhibit
bacterial plaque formation and thus prevent chronic gingivitis. In
this study we tested effects of Prunella vulgaris L. extract (PVE; 5,
10, 25microg/ml) and its component rosmarinic acid (RA; 1microg/ml) on
LPS-induced oxidative damage and inflammation in human gingival
fibroblasts. PVE and RA reduced reactive oxygen species (ROS)
production, intracellular glutathione (GSH) depletion as well as lipid
peroxidation in LPS-treated cells. Treatment with PVE and RA also
inhibited LPS-induced up-regulation of interleukin 1beta (IL-1beta),
interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and
suppressed expression of inducible nitric oxide synthase (iNOS). The
results indicate that PVE and RA are able to suppress LPS-induced
biological changes in gingival fibroblasts. The effects of PVE and RA
are presumably linked to their anti-inflammatory activities and thus
use of PVE and RA may be relevant in modulating the inflammation
process, including periodontal disease.
PMID: 19159670
Rosmarinic acid down-regulates the LPS-induced production of monocyte
chemoattractant protein-1 (MCP-1) and macrophage inflammatory
protein-1alpha (MIP-1alpha) via the MAPK pathway in bone-marrow
derived dendritic cells.
PMID: 18799930
Rosmarinic acid induces melanogenesis through protein kinase A
activation signaling.
PMID: 17651699 [wonder if it will help vitiligo?]
Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA);
inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its
mechanism.
..Topical application RA showed anti-inflammatory activity 5-hours
after 12-tetradecanoylphorbol 13-acetate (TPA) treatment with marked
inhibition of neutrophil infiltration. Up regulation of ICAM-1, VCAM-1
cyclooxygenase-2 (COX-2), KC and MIP-2 by TPA were markedly reduced by
pre-treatment with extract of perilla (PE) or RA... PMID: 15630183
If one way afflicted by PTPN22 C1858T variant, could the following
product be the solution?
www.iherb.com/Life-Extension-Rosmarinic-Acid-Extract-60-Veggie-Caps/15253
Bummer! "Sold Out"
jay
What about NSAIDs derived from a diet high in fruits and veggies?
Would they contain appropriate antioxidants, nutrients, etc to counter
their negative effects which are probably intended toward pathogens?
Kofi
<11611eb6-a610-461e...@s12g2000prs.googlegroups.com>,
jay <jaym...@hotmail.com> wrote:
Consuming something as part of a food is far different than taking it in
pure, concentrated form. Certain fruits and vegetables pose more of a
problem viz. their sugar content than anything else. Any individual
"natural" components which inhibit COX-1 or COX-2 are mixed in with
other substances that interact in complicated ways or they are
themselves capable of acting on multiple targets, which makes it
difficult to study. When that happens, you fall back on epidemiology.
Compare with my recent posts on the benefits of an anti-inflammatory
diet.
If there's enough bowel damage, colitis patients can have problems
digesting foods with heavy amount of fiber but that's a structural
issue, not a biochemical one. Fiber is actually still good for them
when taken in a more soluble form.
jay
> > and proliferation in an Lck-dependent manner.
Pubmed indicates common flavonoids (ie quercetin, apigenin, genistein,
capcasin, etc) have a similar effect: inhibit or kill activated immune
cells (ie Jukrat). It appears flavonoids are anti-pathogen and at the
same time (as if by design) limit body's immune response.
It also appears a PTPN variants could affect the risk of leukemia, as
described in following abstracts:
Receptor Protein Tyrosine Phosphatases in Hematopoietic Cells.
PTPs and PTKs control the level of tyrosine phosphorylation of
cellular proteins. Although many substrates for PTKs have been
identified, the specific targets of individual PTP family members,
along with the consequences of protein dephosphorylation for cellular
physiology, remain largely unknown. Fine regulation of tyrosine
phosphorylation events is required for the proper progression of
hematopoiesis. In this review, we have summarized the characterization
of tyrosine phosphatases in hematopoietic cells and delineated their
potential role in the process of hematopoiesis and the development of
hematopoietic disorders. PMID: 10982240
Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell
acute lymphoblastic leukemia.
PTPN2 (protein tyrosine phosphatase non-receptor type 2, also known as
TC-PTP) is a cytosolic tyrosine phosphatase that functions as a
negative regulator of a variety of tyrosine kinases and other
signaling proteins. In agreement with its role in the regulation of
the immune system, PTPN2 was identified as a susceptibility locus for
autoimmune diseases. In this work, we describe the identification of
focal deletions of PTPN2 in human T-cell acute lymphoblastic leukemia
(T-ALL). Deletion of PTPN2 was specifically found in T-ALLs with
aberrant expression of the TLX1 transcription factor oncogene,
including four cases also expressing the NUP214-ABL1 tyrosine kinase.
Knockdown of PTPN2 increased the proliferation and cytokine
sensitivity of T-ALL cells. In addition, PTPN2 was identified as a
negative regulator of NUP214-ABL1 kinase activity. Our study provides
genetic and functional evidence for a tumor suppressor role of PTPN2
and suggests that expression of PTPN2 may modulate response to
treatment. PMID: 20473312
randall
Jay/Kofi
If this above doesn't say enough, then WHAT?
PUNT... play defense then get back on the OFFENSE.
Aspirin has never helped ME. But now that i'm a glimmer of
my former psor self i TAKE aspirin just to see the effects.
After a few days of around 100mg's i'm not seeing or feeling
anything.
Not that it's bad, i've got folks in my family who lived on the stuff.
And it JUST doesn't fit the paradigm of quality and quantity/life YET
from
my perspective.
OK
Pgd2, isn't pge2?
Never noticed the former?
This is btw the first post with these two in the same post for ALL
groups.
So?
I'm intrigued.
http://en.wikipedia.org/wiki/PGE2
http://en.wikipedia.org/wiki/Prostaglandin_D2
[...] produced by mast cells – recruits Th2 cells,
<snip>
That's a GOOD thing. More IL-10 (a Th2 cell) less Th1/Th17 skew.
The ONE area i've paid moderate attention too is pge2 and not pgd2.
<randall note: is pge2 the hot zone for both of us inflammatory
pathway WISE?>
see:
**a possible reason for the impairment of intestinal wound healing in
IBD.
PMID: 20803697**
Which benefits crohn's and PSORIASIS iirc. :)
The other ONE i've never gave much (any?) thought too, is-->
PGD2
http://en.wikipedia.org/wiki/Prostaglandin_D2
Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the
receptor PTGDR, as well as CRTH2. It is a major prostaglandin produced
by mast cells – _____________________recruits Th2 cells___________,
eosinophils, basophils. In mammalian organs, large amounts of PGD2 are
found in the brain, in mast cells and found nowhere else. It is
critical to development of allergic diseases such as asthma.
Effects
Causes a contraction of the bronchial airways. The concentration of
PGD2 in asthma-patients is 10 times higher than in control patients,
especially after it is brought into contact with allergens. Involved
in the regulation of reducing body temperature in sleep, and acts
opposite to prostaglandin E2.
Causes Vasodilation
<snip>
http://en.wikipedia.org/wiki/PTGDR
Prostaglandin D2 receptor (DP1) is a G-protein coupled receptor,
encoded by the PTGDR gene, for prostaglandin D2
DP1 is a G-protein-coupled receptor. Its activity is mainly mediated
by G-S proteins that stimulate adenylate cyclase resulting in an
elevation of intracellular cAMP and Ca2+.
<sniP>
In psoriasis we have elevated cGMP and NOT elevated cAMP.
To much guanine?
http://en.wikipedia.org/wiki/Guanine
or is it the methyalation or LACK of methylation?
http://en.wikipedia.org/wiki/Methylation
If cg islands aren't wearing their CAPs aren't they open for immune
attacks?
A repitillian profile or something? IOWs non self?
methylation psoria* - 23 hits - pubed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=methylation+psoria*
17 hits for methylation and cron's
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=methylation+crohn's
<don't have time ot check these>
18 hits - psoria* AND cGMP - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=psoria*+AND+cGMP
Susan in our group would say that HPA-axis and stress and to much cGMP
is the causation of psoriasis:
http://en.wikipedia.org/wiki/Cyclic_guanosine_monophosphate
OK so much for the messenger and hpa-axis.
I'm still hooked on SFB being the key in this rube goldberg
machination. LOL
#1 of this search being:
http://www.ncbi.nlm.nih.gov/pubmed/20625148
[...] PMID: 20625148
cAMP and psoria* gets 116 hits - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=psoria*+AND+cAMP
Is the problem LACK of CREM?
I only see two hits for crem for psoria* and four for crohn's on
pubmed.
http://en.wikipedia.org/wiki/CAMP_responsive_element_modulator
cAMP-responsive element modulator is a protein that in humans is
encoded by the CREM gene.[1][2][3]
This gene encodes a bZIP transcription factor that binds to the cAMP
responsive element found in many viral and cellular promoters. It is
an important component of cAMP-mediated signal transduction during the
spermatogenetic cycle, as well as other complex processes. Alternative
promoter and translation initiation site usage allows this gene to
exert spatial and temporal specificity to cAMP responsiveness.
Multiple alternatively spliced transcript variants encoding several
different isoforms have been found for this gene, with some of them
functioning as activators and some as repressors of transcription.[
Interactions
CAMP responsive element modulator has been shown to interact with
FHL5.
<sniP>
FHL5
http://en.wikipedia.org/wiki/FHL5
i'm guessing i'm ok in this department. Got kids. LOL
iHoP'ing it:
http://www.ihop-net.org/UniPub/iHOP/gs/120225.html
JG Krueger with an abstract on CREM that i haven't posted to the P NG:
http://www.ncbi.nlm.nih.gov/pubmed/20152045
BMC Dermatol. 2010 Feb 12;10:1.
Personalized medicine in psoriasis: developing a genomic classifier to
predict histological response to Alefacept.
Suárez-Fariñas M, Shah KR, Haider AS, Krueger JG, Lowes MA.
Laboratory for Investigative Dermatology, The Rockefeller University
1230 York Ave, New York, NY 10065, USA.
Abstract
BACKGROUND: Alefacept treatment is highly effective in a select group
patients with moderate-to-severe psoriasis, and is an ideal candidate
to develop systems to predict who will respond to therapy. A clinical
trial of 22 patients with moderate to severe psoriasis treated with
alefacept was conducted in 2002-2003, as a mechanism of action study.
Patients were classified as responders or non-responders to alefacept
based on histological criteria. Results of the original mechanism of
action study have been published. Peripheral blood was collected at
the start of this clinical trial, and a prior analysis demonstrated
that gene expression in PBMCs differed between responders and non-
responders, however, the analysis performed could not be used to
predict response.
METHODS: Microarray data from PBMCs of 16 of these patients was
analyzed to generate a treatment response classifier. We used a
discriminant analysis method that performs sample classification from
gene expression data, via "nearest shrunken centroid method".
Centroids are the average gene expression for each gene in each class
divided by the within-class standard deviation for that gene.
RESULTS: A disease response classifier using 23 genes was created to
accurately predict response to alefacept (12.3% error rate). While the
genes in this classifier should be considered as a group, some of the
individual genes are of great interest, for example, cAMP response
element modulator (CREM), v-MAF avian musculoaponeurotic fibrosarcoma
oncogene family (MAFF), chloride intracellular channel protein 1
(CLIC1, also called NCC27), NLR family, pyrin domain-containing 1
(NLRP1), and CCL5 (chemokine, cc motif, ligand 5, also called
regulated upon activation, normally T expressed, and presumably
secreted/RANTES).
CONCLUSIONS: Although this study is small, and based on analysis of
existing microarray data, we demonstrate that a treatment response
classifier for alefacept can be created using gene expression of PBMCs
in psoriasis. This preliminary study may provide a useful tool to
predict response of psoriatic patients to alefacept.
PMID: 20152045
How could i let this sliP by?
CREM and cAMP and cGMP and and and inflammation (pge2 and pgD2). LOL
Don't know? LOL
But maybe i was looking at NOS or nitric oxide from these GUYs?
Cruiser or Manfred tried to raise iNOS and do something in these
regards as i recall.
I could google it.
I WILL.
Or just google pgd2 and see what was said in OUR group?
I only see five hits and one of those is from the crohn's group. (kofi
posted and this is what
i'm posting back too.)
5 results for pgd2 - P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=pgd2
NO hits for iNOS and pgd2 on the p ng, but 109 for ALL groups:
http://groups.google.com/groups/search?hl=en&qt_s=1&q=pgd2+inos
ONLY one hit for all GOOGLE groups. To Life extension and it's kofi's
from 2004
http://groups.google.com/group/sci.life-extension/browse_thread/thread/f83bbacd494d48f1/5c85a73a3c8aff7a?hl=en&q=pgd2+inos
[...] niacin interferes with the cAMP/PKA pathway and massively
stimulates
PGD2 formation (perhaps accounting for its benefit in
atherosclerosis);
the major metabolite of PGD2, 15d-PGJ2), is the body's most potent
PPAR-gamma activator [PMID 15037193]; high doses of niacin thin the
hair
[...] GSK-3b enhances TNF-a activation of iNOS and NFKB
signals [PMID 12065308]; TNF-a plus high glucose activates GSK-3b
long
term exposure to TNF-a promotes insulin resistance (compare with my
previous post on TNF-a and allergies)
<snip>
After reading this i recall cruiser was on to arginine and cripes.
Something else kofi posted. LOL
OK i google cruiser and inos and arginine.
OK i get 14 hits for
cruiser inos arginine - all group search:
http://groups.google.com/groups/search?hl=en&qt_s=1&q=cruiser+inos+arginine
Must have been ornithine.
Which i recall Durk and sandy worked on.
120 hits ornithine arginine durk sandy - ALL GROUPs:
http://groups.google.com/groups/search?hl=en&q=ornithine+arginine+durk+sandy&sitesearch=
And by droPPing durk and sandy and putting psoriasis back in:
206 hits - ornithine arginine psoriasis - all groups
http://groups.google.com/groups/search?hl=en&q=ornithine+arginine+psoriasis&sitesearch=
And the first one is CRUISER's.
I see lysine again.
Cruiser did come back with Thiamine and lysine to build digestion.
Which i did for a month or two.
After that i wanted to eat a whole COW, PIG, Poultry and a little
salad. LOL
My digestive juices wanted the kitchen sink. <w>
Let's SEE:
49 hits - pge2 and Crohn's - pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's+pge2
The 1st n that search:
http://www.ncbi.nlm.nih.gov/pubmed/20803697
Inflamm Bowel Dis. 2010 Sep;16(9):1505-13.
Prostaglandin E2 inhibits migration of colonic lamina propria
fibroblasts.
Rieder F, Georgieva M, Schirbel A, Artinger M, Zügner A, Blank M,
Brenmoehl J, Schölmerich J, Rogler G.
Department of Internal Medicine I, University of Regensburg,
Regensburg, Germany. florian...@t-online.de
Abstract
BACKGROUND: Migration of colonic lamina propria fibroblasts (CLPF) is
an important mechanism during wound healing in inflammatory bowel
disease (IBD). The concentration of prostaglandin E2 (PGE2) is
increased in the intestinal mucosa of IBD patients. We therefore
investigated the role of PGE2 in CLPF migration.
METHODS: Primary cultures of CLPF were isolated from healthy controls
and Crohn's disease patients. Migration assays were performed in the
Boyden chamber and scratch assays. EP receptors, PGE2, intracellular
cyclic adenosine monophosphate (cAMP), expression and distribution of
F-actin, alpha-smooth muscle actin (SMA), and myosin light chain (MLC)
were determined by immunoblotting, immunocytochemistry, and enzyme-
linked immunosorbent assay (ELISA).
RESULTS: All four EP receptor subtypes were present on CLPF. PGE2 and
agonists to the EP2 and EP4 receptor reduced the migration of CLPF.
Blockade of the EP2 and the EP4 receptor inhibited the effect of PGE2
on CLPF migration. An increase in intracellular cAMP reduced CLPF
migration. PGE2 increased the concentrations of cAMP in CLPF, with
abrogation after addition of EP2 and EP4 receptor antagonists. PGE2
and forskolin decreased the expression of alpha-SMA and F-actin and
reduced cell polarization and lamellipodium formation in a scratch
assay. In addition, forskolin reduced the phosphorylation of MLC
(pMLC) and led to lack of accumulation of pMLC in the leading edge of
CLPF.
CONCLUSIONS: PGE2 reduced the migration of CLPF via elevation of
intracellular cAMP. Potential mechanisms are changes in expression of
cytoskeletal proteins, failure of CLPF to polarize, and a decreased
amount of pMLC. This might be a possible reason for the impairment of
intestinal wound healing in IBD.
PMID: 20803697
2 hits : crohn's pgd2 - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=crohn's+pgd2
one from 2005 and one from 1991?
74 hits - intestinal cells pgd2 - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=intestinal+cells+pgd2
28 hits - intestinal mast cells pgd2 - pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=intestinal+mast+cells+pgd2
I think the real problem is still pge2
A little aspirin will screw just fine with it and FLARE my HIDE.
But not now as SFB is so low i don't FLARE much at ALL.
But i'm working at bringing it back enough to KNOCK DOWN AGAIN>
Take one for the TEAM or the GiPPer. LOL
==================
you said:
er' i said:
> But i'm not seeing crohn's or psor in the most recent of all ptpn22's
> abstract.
and you posted:
http://www.ncbi.nlm.nih.gov/pubmed/18923449
6 results for PMID: 18923449
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=PMID%3A+18923449+&start=0&scoring=d&hl=en&
So i wasn't to FAR off track.
randall ...... ONE ADAM 3 to the rescure? If ONLY...& it was
1adam12....
randall
hi
The search of methylation and crohn's in the last post.
I checked it.
#1 in that search:
http://www.ncbi.nlm.nih.gov/pubmed/20950376
Clin Genet. 2010 Sep 16. doi: 10.1111/j.1399-0004.2010.01546.x.
Identification of disease-associated DNA methylation in intestinal
tissues from patients with inflammatory bowel disease.
Lin Z, Hegarty J, Cappel J, Yu W, Chen X, Faber P, Wang Y, Kelly A,
Poritz L, Peterson B, Schreiber S, Fan JB, Koltun W.
Department of Surgery, The Pennsylvania State University College of
Medicine, Hershey, PA, USA Department of Biostatistics, Vanderbilt
University, Nashville, TN, USA Institute of Molecular Medicine, The
Cleveland Clinic, Cleveland, OH, USA Department of Cell and Molecular
Physiology, The Pennsylvania State University College of Medicine,
Hershey, PA, USA Institute for Clinical Molecular Biology, Christian-
Albrechts-University, Kiel, Germany Illumina Inc., San Diego, CA, USA.
Abstract
Lin Z, Hegarty JP, Cappel JA, Yu W, Chen X, Faber P, Wang Y, Kelly AA,
Poritz LS, Peterson BZ, Schreiber S, Fan J-B, Koltun WA.
Identification of disease-associated DNA methylation in intestinal
tissues from patients with inflammatory bowel disease. Overwhelming
evidence supports the theory that inflammatory bowel disease (IBD) is
caused by a complex interplay between genetic predispositions of
multiple genes, combined with an abnormal interaction with
environmental factors. It is becoming apparent that epigenetic factors
can have a significant contribution in the pathogenesis of disease.
Changes in the methylation state of IBD-associated genes could
significantly alter levels of gene expression, potentially
contributing to disease onset and progression. We have explored the
role of DNA methylation in IBD pathogenesis. DNA methylation profiles
(1505 CpG sites of 807 genes) of matched diseased (n = 26) and non-
diseased (n = 26) intestinal tissues from 26 patients with IBD
[Crohn's disease (CD) n = 9, ulcerative colitis (UC) n = 17] were
profiled using the GoldenGate methylation assay. After an initial
identification of a panel of 50 differentially methylated CpG sites
from a training set (14 non-diseased and 14 diseased tissues) and
subsequent validation with a testing set (12 non-diseased and 12
diseased tissues), we identified seven CpG sites that are
differentially methylated in intestinal tissues of IBD patients. We
have also identified changes in DNA methylation associated with the
two major IBD subtypes, CD and UC. This study reports IBD-associated
changes in DNA methylation in intestinal tissue, which may be disease
subtype-specific.
PMID: 20950376
If it's epigenetic you change your Gi tract?
CpG islands pop up due to what exactly?
159 hits - cpg methylation inflammat* - pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=cpg+methylation+inflammat*
http://en.wikipedia.org/wiki/Epigenetics
http://en.wikipedia.org/wiki/CpG_island
<see thymines>
I only wonder if the NEED for thymines doesn't glue up some pathways?
http://en.wikipedia.org/wiki/Thymine
randall... oh well... time is short...
Kofi
remission in ulcerative colitis is associated with high levels of PGD2;
people in long-term remission of ulcerative colitis have elevated levels
of the same chemical, prostaglandin D2, which they previously found to
be important in promoting healing and maintaining remission of the
condition in laboratory rats
<http://www.medicalnewstoday.com/articles/191764.php>;
<http://www.sciencedaily.com/releases/2010/06/100614160155.htm>, [Linda
Vong, Jose G. P. Ferraz, Remo Panaccione, Paul L. Beck, John L. Wallace.
A pro-resolution mediator, prostaglandin D2, is specifically
up-regulated in individuals in long-term remission from ulcerative
colitis. Proceedings of the National Academy of Sciences, 2010; DOI:
10.1073/pnas.1004982107]
atherosclerotic plaques rupture when they contain more prostaglandin E2
than PGD2 (which would associate more with NFKB and MMP-9
downregulation); COX-2 inhibition is only protective when the pathway
tilts more toward PGD2 [PMID 15155382]
niacin interferes with the cAMP/PKA pathway and massively stimulates
PGD2 formation (perhaps accounting for its benefit in atherosclerosis);
the major metabolite of PGD2, 15d-PGJ2, is the bodyąs most potent
PPARgamma activator [PMID 15037193]
smoking has the opposite effect as olive oil on adrenergic receptors;;
ADRB2 is downregulated in the lymphocytes of smokers (and smoking
worsens Crohnąs/cardiomyopathy); also downregulated: PIK3CG, FASLG,
IL18RAP (IL-18 is upregulated in atherosclerosis and part of the
HPA/ACTH axis), IL2RB (crucial for Tregs), TGFBR3, TNFRSF14, CX3CR1,
ABCB1, CDKN1C, RHOC, SLC1A7, CD38, HMOX1, PTGDS (lipocalin-type
prostaglandin D2 synthase - important for Crohnąs), PTGDR (binding
target for PGD2), PTPN6, CD247, CD300A; upregulated: PLA2G7 (a PLA2
isoform), RNASE2, S100A8, S100A12, IL13RA1, LDHA, CYP1B1, NRG1
(neuregulin-1; downregulation is associated with schizophrenia and
glutamatergic hypofunction; NRG1 activates ERBB receptors releasing a
factor, EBP1, known to inhibit the influenza virus transcriptase),
MGST1, GZMB, PRF1; natural-killer cell genes were depressed, consistent
with NK cell hypofunction in smokers
<http://www.sciencedaily.com/releases/2010/07/100713165057.htm>, [Jac C
Charlesworth, Joanne E Curran, Matthew P Johnson, Harald HH Goring,
Thomas D Dyer, Vincent P Diego, Jack W Kent Jr, Micheal C Mahaney, Laura
Almasy, Jean W MacCluer, Eric K Moses and John Blangero. Transcriptomic
epidemiology of smoking: the effect of smoking on gene expression in
lymphocytes. BMC Medical Genomics, 2010; (in press)]
overexpression of AKR1C3 in breast cancer reduces the antiproliferative
qualities of PGD2/PGJ2 (PPARgamma?) and encourages estrogen receptor
alpha induced proliferation via its effect on estrone which increases
the 17beta-estradiol:progesterone ratio [PMID 20036328]
mice deprived of REM sleep suffer a drop in PGD2
<http://www.websciences.org/cftemplate/NAPS/archives/indiv.cfm?ID=1996455
9> and PGD2 is a potent, endogenous sleep-promoter
<http://www.obi.or.jp/english/introduction/behavioral.html>
The 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an
endogenous ligand of PPAR-gamma, a potent anti-inflammatory mediator;
intraplantar administration of 15d-PGJ(2) (30-300 ng/paw) inhibits the
mechanical hypernociception/inflammation induced by both carrageenan
(100 mug/paw) and the directly acting hypernociceptive mediator, PGE2.
Moreover, 15d-PGJ(2) [100 ng/temporomandibular joint (TMJ)] inhibits
formalin-induced TMJ hypernociception but the direct administration of
15d-PGJ(2) into the dorsal root ganglion was ineffective in blocking
PGE(2)-induced hypernociception; 15d-PGJ(2) antinociception was enhanced
by the increase of macrophage population in paw tissue due to local
injection of thioglycollate, suggesting the involvement of these cells
on the 15d-PGJ(2)-antinociceptive effect. Moreover, the antinociceptive
effect of 15d-PGJ(2) was blocked by naloxone and by a PPAR-gamma
antagonist, suggesting the involvement of peripheral opioids and
PPAR-gamma receptor in the process. Similar to opioids, the 15d-PGJ(2)
antinociceptive action depends on the nitric oxide/cGMP/protein kinase G
(PKG)/K(ATP)(+) channel pathway because it was prevented by the
pretreatment with the inhibitors of nitric-oxide synthase
(N(G)-monomethyl-l-arginine acetate), guanylate
cyclase]1H-(1,2,4)-oxadiazolo(4,2-alpha)quinoxalin-1-one[, PKG
[indolo[2,3-a]pyrrolo[3,4-c]carbazole aglycone (KT5823)], or with the
ATP-sensitive potassium channel blocker glibenclamide; 15d-PGJ(2)
inhibits inflammatory hypernociception via PPAR-gamma activation. This
effect seems to be dependent on endogenous opioids and local macrophages
[PMID 17928570]; 15d-PGJ(2) has a potential peripheral antinociceptive
and anti-inflammatory effect in the TMJ via PPAR-gamma activation. The
results also suggest that 15d-PGJ(2) induced-peripheral antinociceptive
response in the TMJ is mediated by kappa/delta opioid receptors by the
activation of the intracellular l-arginine/NO/cGMP/K(+)(ATP) channel
pathway. The pharmacological properties of the peripheral administration
of 15d-PGJ(2) highlight the potential use of this PPAR-gamma agonist on
TMJ inflammatory pain conditions [PMID 19647045]
FYI, niacin - which produces PGD2 to cause flushing - binds to a
receptor that also accepts butyrate and BHB (elevated by ketogenic
diets).
>
> OK i google cruiser and inos and arginine.
>
Do not mix arginine with colitis. It stimulates nitric oxide release -
and not the good kind. It also affects mTOR in the wrong direction for
immunotolerance.
>
> I think the real problem is still pge2
>
If you block PGE2, you block intestinal repair - stem cells need PGE2.
You also block Tregs. You also block the ability of the immune system
to respond to pathogens. PGE2 is NOT a good target in this inflammatory
loop.
Kofi
poorly understood and is currently viewed as a biopsychosocial disorder
with symptoms mediated via the brain-gut axis. Epidemiological studies
of IBS point to risk factors such as familial clustering, sexual abuse
and other forms of childhood trauma, low birth weight and
gastrointestinal infection. Epigenetics focuses on the complex and
dynamic interaction between the DNA sequence, DNA modifications and
environmental factors, all of which combine to produce the phenotype.
Studies in animal models of early stress and in humans who have
experienced childhood trauma or abuse suggest that these events can lead
to long-lasting epigenetic changes in the glucocorticoid receptor gene
brought about by hypermethylation of a key regulatory component. Animal
studies also indicate that the microbiota has a pivotal role in
programming the core stress system, the hypothalamic-pituitary-adrenal
axis and the immune system through epigenetic mechanisms. In this
Perspectives, an epigenetic model of IBS is presented that incorporates
many of the current findings regarding IBS, including proinflammatory
markers, neuroendocrine alterations and links with both psychosocial
stress and stress related to infection. We conclude that applying
epigenetic methodology to this common and disabling disorder may help
unravel its complex pathophysiology and lead to more effective
treatments [PMID 20585338]
the results of this paper were recently paraphrased in a review by
Dinan, et al., "IBS: An Epigenetic Perspective": łMeaney and colleagues
have explored a related model in which rat mothers are separated into
those with high nursing and licking/grooming behavior (aBn-LG) and those
with low levels of such behavior. Pups reared by Śhighą aBn-LG mothers
have high levels of glucocorticoid receptors in the hippocampus and
overall more effective negative feedback mechanisms in the HPA. these
effects are epigenetically transferred as a result of the maternal
behavior. Pups raised by Ślową aBnG-LG mothers have higher levels of
methylation in the promoter region of the glucocorticoid receptor gene
and a decrease in the binding of nerve growth factor-inducible protein A
(NGF-IA = EGR-1 = Zif268 = Krox-24 = TIS8 = ZENK) transcription factor
to the promoter region of glucocorticoid receptor (GR) gene.
Intriguingly, when adult rats raised by Śhighą aBnG-LG mothers are
injected intra cerebroventricularly with l-methionine (a methyl group
donor) the early environmental effects are negated.˛ results from [PMID
18513204]
randall
> > Pgd2, isn't pge2?
>
> remission in ulcerative colitis is associated with high levels of PGD2;
> people in long-term remission of ulcerative colitis have elevated levels
> of the same chemical, prostaglandin D2, which they previously found to
> be important in promoting healing and maintaining remission of the
> condition in laboratory rats
> <http://www.medicalnewstoday.com/articles/191764.php>;
> <http://www.sciencedaily.com/releases/2010/06/100614160155.htm>, [Linda
> Vong, Jose G. P. Ferraz, Remo Panaccione, Paul L. Beck, John L. Wallace.
> A pro-resolution mediator, prostaglandin D2, is specifically
> up-regulated in individuals in long-term remission from ulcerative
> colitis. Proceedings of the National Academy of Sciences, 2010; DOI:
> 10.1073/pnas.1004982107]
OK just so we have the pmid #.
http://www.ncbi.nlm.nih.gov/pubmed/20547854
A pro-resolution mediator, prostaglandin D(2), is specifically up-
regulated in individuals in long-term remission from ulcerative
colitis.
Vong L, Ferraz JG, Panaccione R, Beck PL, Wallace JL.
[...] pmid: 20547854
WALLACE has seven hits for pgd2 on pubmed::
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=pgd2+wallace
xlnt.-------------------------> remember to LOOK at them.... later.
The entire study is here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900663/
I'll take some time tonight and have a nice glass of CAB/resveratrol.
Yet if what i've already DONE is letting this Th2 denizen set up shop
i'd LOVE to KNOW.
I want to keep pgd2 in the colon/small intestine neighborhood forever
it sounds like.
? Your diet does it kofi?
As a side to that.
While i did my resveratrol trials for a few years i was very clear.
Resveratrol ended all my other trials for three years.
I waited six months for the effects to reverse.
So i might do the jungle fern trial or halofuginone from hydrangea
trial.
Never got to either one:
keywords: Calaguala -extract from Polypodium decumanum, cotochuPa,
Polypodium Leucotomos, Kalawalla etc
Back to in vino veritas
http://en.wikipedia.org/wiki/In_vino_veritas
I hope i don't need to do those jungle fern TRIALs now as i'm too
clear. LOL
Still might add in some hydrangea/ halofugione root for grins.
I'll post some info on the res i took below.
Bill SARDi has become a good friend as a result of RES in ME. LOL
>
> atherosclerotic plaques rupture when they contain more prostaglandin E2
> than PGD2 (which would associate more with NFKB and MMP-9
> downregulation); COX-2 inhibition is only protective when the pathway
> tilts more toward PGD2 [PMID 15155382]
http://www.ncbi.nlm.nih.gov/pubmed/15155382
will look...
>
> niacin interferes with the cAMP/PKA pathway and massively stimulates
> PGD2 formation (perhaps accounting for its benefit in atherosclerosis);
> the major metabolite of PGD2, 15d-PGJ2, is the body¹s most potent
> PPARgamma activator [PMID 15037193]
>
http://www.ncbi.nlm.nih.gov/pubmed/15037193
ditto
> smoking has the opposite effect as olive oil on adrenergic receptors;;
> ADRB2 is downregulated in the lymphocytes of smokers (and smoking
> worsens Crohn¹s/cardiomyopathy); also downregulated: PIK3CG, FASLG,
> IL18RAP (IL-18 is upregulated in atherosclerosis and part of the
> HPA/ACTH axis), IL2RB (crucial for Tregs), TGFBR3, TNFRSF14, CX3CR1,
> ABCB1, CDKN1C, RHOC, SLC1A7, CD38, HMOX1, PTGDS (lipocalin-type
> prostaglandin D2 synthase - important for Crohn¹s), PTGDR (binding
> target for PGD2), PTPN6, CD247, CD300A; upregulated: PLA2G7 (a PLA2
> isoform), RNASE2, S100A8, S100A12, IL13RA1, LDHA, CYP1B1, NRG1
> (neuregulin-1; downregulation is associated with schizophrenia and
> glutamatergic hypofunction; NRG1 activates ERBB receptors releasing a
> factor, EBP1, known to inhibit the influenza virus transcriptase),
> MGST1, GZMB, PRF1; natural-killer cell genes were depressed, consistent
> with NK cell hypofunction in smokers
> <http://www.sciencedaily.com/releases/2010/07/100713165057.htm>, [Jac C
> Charlesworth, Joanne E Curran, Matthew P Johnson, Harald HH Goring,
> Thomas D Dyer, Vincent P Diego, Jack W Kent Jr, Micheal C Mahaney, Laura
> Almasy, Jean W MacCluer, Eric K Moses and John Blangero. Transcriptomic
> epidemiology of smoking: the effect of smoking on gene expression in
> lymphocytes. BMC Medical Genomics, 2010; (in press)]
>
> overexpression of AKR1C3 in breast cancer reduces the antiproliferative
> qualities of PGD2/PGJ2 (PPARgamma?) and encourages estrogen receptor
> alpha induced proliferation via its effect on estrone which increases
> the 17beta-estradiol:progesterone ratio [PMID 20036328]
>
> mice deprived of REM sleep suffer a drop in PGD2
> <http://www.websciences.org/cftemplate/NAPS/archives/indiv.cfm?ID=1996455
> 9> and PGD2 is a potent, endogenous sleep-promoter
> <http://www.obi.or.jp/english/introduction/behavioral.html>
Never felt like i slept deep enough.
TILL i took melatonin one day.
Then added in 5HTP
5HTP and Melatonin have been life saver's over the YEARs.
Might try some LDN even.
It certainly has helped some in our group.
low dose naltrexone must have even more to it then they know, i
suspect.
http://www.lowdosenaltrexone.org/
http://www.ncbi.nlm.nih.gov/pubmed/19647045
>
> FYI, niacin - which produces PGD2 to cause flushing - binds to a
> receptor that also accepts butyrate and BHB (elevated by ketogenic
> diets).
Very KEY no doubt.
Where is your diet located?
I suppose i can google you.
Only 3820 hits LOL
http://groups.google.com/groups/search?hl=en&qt_s=1&q=kofi+diet
I'll do some follow up to nail your state of the ART today version.
>
>
>
> > OK i google cruiser and inos and arginine.
>
> Do not mix arginine with colitis. It stimulates nitric oxide release -
> and not the good kind. It also affects mTOR in the wrong direction for
> immunotolerance.
DO NOT MIX ARGININE/ORNITHINE WITH PSORIASIS EITHER.
Found that out after reading durk/sandy LIFE EXTENSION a practical
scientific approach. 1982c
I see they dedicated to Denham Harman, Hoffman, WATSON and CRICK
I found it out the hard way on arginine and L. glutamine the flarish
effects.
Will have to go back to them after I clear 100% and see if their
allies and not enema's. LOL
er' enemies of the GUT FLORA or just a pain in or on the skin?
By using them and flaring up psor wise i do feel wiser. LOL
aND
At a time when I was quite severe to begin with.
>
>
>
> > I think the real problem is still pge2
>
> If you block PGE2, you block intestinal repair - stem cells need PGE2.
> You also block Tregs. You also block the ability of the immune system
> to respond to pathogens. PGE2 is NOT a good target in this inflammatory
> loop.
Never tried to BLOCK.
Back in the early 90's or 1994 iirc i cut out as much w6 (n6 omega-6)
as possible
and cleared about 35% over the next two months.
Then plateaued.
But just that was key for me.
As diet never really lent the clues to allow such a massive continuous
clearing.
I was hooked after that.
And luckilly found the wit kit in 1999, after trying Robert Grays
Colon Cleansing and WAYs to rebuild lactic loving bugs.
Wait.. that was bernard jensen
http://www.bibkit.com/experts.html
I tried both of them back THEN.
They talked a good game anyway.
Gray was The COLON Health Handbook.
His fermented wheat berry rejuvelac simply never worked.
Not that i didn't try. over and over...
Later i was told that human sourced LAB had the hooks to hold on or
something to that effect. The wheat grass and berry LAB didn't?
But by ONLY drinking it, simply seems that such a severe diet is
neccessay
to duplicate the situation when LAB is forming in the infant Gi tract
as being obtrusive and not something folks will do. Much easier to
use the wit kit and tube it in.
http://groups.google.com/groups/search?hl=en&q=robert+gray+rejuvelac&btnG=Search&sitesearch=
This person seems to think the rejuvelac is GOOD.
http://www.sheilashea.com/constipation.html
I did NOT try the cabbage version. It seemed like GRAY changed
formula's frequently through
dozens of editions of his book. I have three revised editions before
i said screw it.
I did like the HOLISTIC HORIZONs products at the time and felt they
were beneficial,
but not for the long term as i would simply regress after the
treatments slowly
but surely every time.
OK... res time?
Yes..
Go find some?
OK..
===========================
A big AD for this stuff.
I love this stuff.
I wonder what it does with pgd2?
Does it increase it?
I'll check it next. :)
Longevinex® Produces Heart-Healthiest Laboratory Rats In The World;
Nutriceutical Has Profound Effect Upon Cholesterol-Fed Animals.
Las Vegas, NV (November 8, 2010) – According to the latest published
research, the heart-healthiest laboratory animals in the world are
taking Longevinex®, a red wine pill dietary supplement.
Researchers gave cholesterol-fed rabbits Longevinex®, a proprietary
blend of red wine molecules (resveratrol, quercetin, ferulic acid)
plus rice bran IP6 and vitamin D3, and found this dietary supplement:
· More than halves circulating total cholesterol among
cholesterol-fed animals.
· Cuts arterial plaque (the stuff that sticks to artery walls)
by more than half.
· Reduces the area of damage to the heart following heart
attack by 30%-40%, thus sparing the animal’s life.
· Improves the heart-pumping action of the heart following a
heart attack.
· Improves blood flow in both the aorta (first blood vessel
outside the heart) and in the four coronary arteries that supply the
heart with oxygenated blood, following an intentionally-induced heart
attack.
Rabbit owners can feed their pets Longevinex®, knowing they will be
the heart-healthiest animals in the world. The study, entitled
“Reduction of blood cholesterol and ischemic injury in the
hypercholesteromic rabbit with modified resveratrol, Longevinex®,” was
published in the journal of Molecular & Cellular Biochemistry.
Oh man there are two charts i can't find a link too...
Oh well.
Maybe on their site?
To learn more about Longevinex®,
http://www.longevinex.com/
For science geeks:
http://www.longevinex.com/articles/
Commentary: Longevinex® Lowers Cholesterol, Improves Circulation in
Cholesterol-Fed Rabbits
Commentary: The recently published study in Molecular & Cellular
Biochemistry showing a resveratrol-based nutriceutical (Longevinex®,
pronounced long-jev-in-ex)) significantly reduces circulating levels
of cholesterol and improved blood circulation in cholesterol-fed
rabbits is noteworthy, but probably for reasons other than what most
health-minded readers would assume.
Circulating cholesterol levels are not associated with coronary artery
disease in healthy individuals, despite what you may have read
elsewhere. But the Longevinex® trial IS significant because, in
humans, the accumulation of stored iron and copper in the liver leads
to fatty liver, a condition that is found in about 35% of American
adults. Longevinex® is a matrix of mineral-chelating (key-lay-ting)
small molecules derived from botanical sources that is intended to
control metallic minerals such as iron and copper, as well as calcium.
A very recent study shows as iron accumulates in the liver with
advancing age, several enzymes involved in the natural synthesis of
cholesterol are activated in the liver. There is, however, no
significant relationship between iron levels in the liver and
circulating cholesterol (which is what doctors measure). This means
that this Longevinex® study is more pertinent in heading off or
reversal of fatty liver than it is any alleged prevention of
cholesterol plaque buildup in arteries.
This does not mean that Longevinex® provides no potential benefits for
consumers interested in heart health. In fact, Longevinex® is the
first branded resveratrol pill to exhibit cardio-protection, that is,
protects the heart from damage during a heart attack (animal study),
thus averting sudden cardiac death. Resveratrol, a key ingredient in
Longevinex®, is also known to thin the blood like aspirin, preventing
clots that may block circulation of oxygenated blood to the heart.
Resveratrol has been shown to release, before a heart attack, three
protective molecules, adenosine, nitric oxide and heme oxygenase, that
are otherwise only produced following a heart attack.
Not a real-world test
If it can be assumed that animal studies are reflective of what goes
on in humans, then this study is of some value. However, it is not a
real world test. The animals are engorged with a high-cholesterol
diet, something that is not particularly reflective of human practice
unless one eats a lot of cholesterol-rich eggs every day. Only about
20% of the cholesterol in the human body comes from the diet, the rest
is made naturally in the liver. Dietary cholesterol has little impact
upon circulating cholesterol levels. Where the modern world went
wrong was when refined sugar, not cholesterol, became widely available
and laced into all manner of processed foods (bread, salad dressings,
ketchup, soups, etc.).
Humans will some day realize they have been conned about cholesterol
in order to sell pills. In a healthy state, the liver naturally
produces cholesterol. Cholesterol is required for sex drive and
procreation since sex hormones (testosterone, estrogen) are
synthesized from cholesterol. Cholesterol also transports
antioxidants like vitamin E and carotenoids (beta carotene, lutein,
lycopene) to tissues, and is needed for mood maintenance. Too-low
cholesterol increases the risk for mental depression.
Furthermore, cholesterol is not the primary cause of coronary artery
disease or arterial plaque. Only about 3% of plaque found in human
arteries is cholesterol, while 50% is calcium. When the French
Paradox was first described by Dr. Serge Renaud in the early 1990s,
the paradox was that the French consume a relatively high-fat diet and
have a bit higher cholesterol levels than North Americans, yet their
mortality rate due to coronary artery disease is ~90 per 100,000
versus 240 per 100,000 in the U.S.
But then again, maybe it wasn’t cholesterol that causes coronary
artery disease at all! There are a number of studies which now
indicate high cholesterol is protective and healthy.
· For example, a puzzling question is why, since 1970, as the
consumption of fat increased and circulating cholesterol levels rose,
did Japan experience a reduction in mortality from coronary heart
disease?
· We know that more than 80% of deaths due to coronary heart
disease or stroke occur in patients over 65 years of age. Yet, a
review of observational studies reveals that all-cause mortality was
highest when the circulating cholesterol number was lowest among 80+-
year olds. Among 302 Japanese centenarians, higher cholesterol levels
were associated with better physical and mental function.
· In a study of 9,571 patients who had experienced a heart
attack, patients with higher LDL cholesterol (so-called “bad”
cholesterol) has more favorable outcomes after treatment.
· Duke University researchers recently explored a paradox.
Among 84,429 patients with acute heart problems (chest pain- angina),
high circulating cholesterol was associated with a 29-42% relative
reduced risk for mortality.
· So-called HDL “good” cholesterol isn’t always good. It can
promote inflammation.
· It is interesting to note that the total cholesterol and
blood pressure for men aged 40-49 years have been similar in Japan and
the United States throughout their lifetimes, but coronary heart
disease remains every low in Japan, despite increased dietary fat
intake. The Japanese have lower arterial calcium scores, not lower
cholesterol numbers.
An earlier published animal study showed that resveratrol suppresses
arterial plaque without affecting blood cholesterol levels. It is
important for consumers to realize resveratrol may be beneficial
without affecting cholesterol levels.
Please direct your questions regarding Longevinex and resveratrol to
in...@longevinex.com – Bill Sardi, © 2010, Resveratrol Partners LLC
http://www.ncbi.nlm.nih.gov/pubmed/21052791
Molecular & Cellular Biochemistry 2010 Nov 4.
Reduction of blood cholesterol and ischemic injury in the
hypercholesteromic rabbits with modified resveratrol, Longevinex®
Juhaz B, Das DK, Kertesz A, Juhasz A, Gesztelyi R, Varga B.
Department of Pharmaceutical Sciences, University of Debrecen,
Debrecen, Hungary.
Abstract
The present study examined the efficacy of using Longevinex, a
commercially available resveratrol formulation, to lower blood
cholesterol in hypercholesteromic rabbits. New Zealand white rabbits
were randomly divided into two groups (n = 6 per group), one group was
given high cholesterol diet for 3 months while the other group fed
regular diet served as control. The high cholesterol diet fed group
was further subdivided into two groups (n = 6 per group), one group
was given Longevinex resveratrol while the other group given vehicle
only served as control. Longevinex was given by gavaging up to a
period of 6 months. Longevinex-treated rabbits exhibited lowering of
plasma cholesterol level. Inhibition of arterial plaque formation was
noticed even after 1 month. Longevinex-treated hearts demonstrated
improved ventricular recovery when isolated working hearts were
subjected to 30 min of ischemia followed by 2 h of reperfusion. Aortic
flow and developed pressure during post-ischemic reperfusion period
were significantly higher for the Longevinex-treated hearts compared
to those in control group of hearts. Myocardial infarct size was also
lower in the treated group compared to that for the untreated group.
These results indicate cholesterol-lowering ability of Longevinex,
which appears to reflect in its ability to protect the
hypercholesteromic hearts from ischemic reperfusion injury. PMID:
21052791
===============================
http://www.medicalnewstoday.com/articles/180641.php
Resveratrol May Replace Aspirin As Heart Protector; Longevinex® First
Branded Resveratrol Pill Successfully Tested During Heart Attack
With the realization that half of the people experiencing a sudden
mortal heart attack were taking aspirin on the day of their demise,
researchers have begun to search for a more reliable alternative, and
they may have found it in a red wine molecule called resveratrol (rez-
vair-ah-trawl).
Researchers at the University of Connecticut induced heart attacks in
animals and found resveratrol significantly reduces damage to heart
muscle. Scarring and fibrosis were limited and the animals survived an
otherwise mortal event.
Dipak Das, Ph.D., Sc.D., MD (hon), professor and director of the
Cardiovascular Research Center at the University of Connecticut,
School of Medicine in Farmington, Connecticut, says resveratrol
provokes a "pre-conditioning effect" whereby antioxidant defenses in
the heart are switched on prior to a heart attack, therefore limiting
damage to heart muscle should such an event occur.
Das says: "Resveratrol likely fulfills the definition of a
pharmacological preconditioning compound and gives hope for the
therapeutic promise of alternative medicine." 1 Das goes on to say
resveratrol's preconditioning effect is "the best yet devised method
of cardioprotection."2
The dosage of resveratrol is critical in producing the pre-
conditioning effect Dr. Das found the human equivalent dosage of
175-350 milligrams reduced damage to the heart during a heart attack,
while ten times greater dose (1750-3500 mg) increased the area of
damaged cardiac tissue.
A branded resveratrol pill, Longevinex®, was found to afford the same
level of protection at a much lower dose 100 milligrams of
resveratrol, which may be due to its micronized, micronencapsulated
delivery system and combination with other antioxidants (quercetin,
rice bran, vitamin D and ferulic acid).
Since resveratrol also thins the blood and inhibits clots that form in
coronary arteries in a similar fashion to aspirin, and exhibits other
beneficial properties, such as anti-adhesion factors that inhibit
plaque from sticking to artery walls, it may be superior to aspirin.
Wine consumption is also believed to afford similar protection for the
heart. The red wine-drinking French exhibit a coronary heart disease
mortality rate that is extremely low 90 per 100,000 versus 240 per
100,000 in North America.
The amount of resveratrol in 3 to 5 glasses of red wine is only about
3-5 milligrams, but the heart protective effect is believed to be
produced by the total polyphenolic molecules in a glass of dark, aged
red wine, ~60 milligrams per 5-ounce glass. The optimal health benefit
derived from red wine is achieved at a consumption level of 3-5
glasses, which would be considerably more expensive than a resveratrol
pill, and certainly pose the problem of inebriation.
The heart preconditioning effect of resveratrol is produced by the
natural release of adenosine, which is actually employed as a drug to
restore natural heart rhythm.
Background Information: resveratrol/ Longevinex® pill as alternative
to aspirin
-- It has been widely known that modest impairment of circulation to
the heart for a short duration pre-conditions cardiac tissues to
withstand a full-blown myocardial infarction (heart attack). Since
this discovery, the search for a pre-conditioning agent has been on
the minds of many researchers.
-- The primary target group for an oral preconditioning agent is
adults over age 55 as 96% of all deaths from ischemic heart disease
(lack of oxygen supply to the heart) occur among adults age 55 and
over. A smaller but more targeted group for a preconditioning agent
would be adults with prior heart attack. About half of all
cardiovascular deaths occur in individuals with a previous myocardial
infarction or stroke. In people with a previous heart attack or a
stroke, without any treatment, cardiovascular disease mortality is
about 5% per year for life. 3
-- Pre-clinical studies in animals (University of Connecticut,
unpublished) reveals that resveratrol is such a pre-conditioning agent
and that Longevinex®, a resveratrol-based nutriceutical, appears to
exert similar protection at a far lower and safer dose.
-- Daily aspirin isn't advised for people who have a low risk of a
heart attack or a stroke.
-- About 8 first heart attacks were prevented for every 1,000 men who
took aspirin. However, aspirin doesn't lower the chance of a heart
attack in women.4 Aspirin only reduces the risk of a second mortal
heart attack by about 10%.5
-- According to authoritative studies, aspirin reduces the risk of a
heart attack by about 50 percent.6
-- It does so by thinning the blood and inhibiting blood clots in any
of the four coronary arteries.
-- The best use of aspirin may be its availability at the time of
angina or a heart attack. An aspirin tablet may not be available at
the onset of a heart attack.7
-- Even with all the positive information about aspirin therapy, the
absolute risk for stroke or heart attacks among patients receiving
aspirin therapy remains relatively high, 8-18% after two years. [Rev
Cardiovascular Medicine 5:156-63, 2004] But about half the people who
will experience a heart attack are daily aspirin users.
-- Attention is given to the cost effectiveness of aspirin. It takes
over 2 million aspirin tablets, or $160,000 of pills, to prevent just
one heart attack.
-- Approximately 1 in 15 individuals will experience an aspirin-
induced complication and 1 in 556 individuals will die.8
-- Aspirin does significantly reduce the relative risk for all-cause
death among coronary artery disease patients (0.80 relative risk
compared to placebo, ~20% relative risk reduction) but also increases
the risk for major bleeding episodes (hemorrhagic stroke) by 1.87.9
-- In 1999 it was first reported that resveratrol and quercetin, two
molecules commonly found in red wine, produce increased adenosine
levels in blood plasma and may serve as preconditioning agents.10
-- In subsequent animal experiments, resveratrol was shown to increase
adenosine availability and to improve recovery following a heart
attack.11
-- Dipak Das of the Cardiovascular Research Center at the University
of Connecticut School of Medicine has gone on to describe resveratrol
preconditioning effect as opposed to the direct action of conventional
pharmaceutic agents.
-- Das says: "Resveratrol likely fulfills the definition of a
pharmacological preconditioning compound and gives hope for the
therapeutic promise of alternative medicine." 12 Das goes on to say
resveratrol's preconditioning effect is "the best yet devised method
of cardioprotection."13
References
<snip>
OH WELL.
Didn't mean to go on this long.
will find more to add on soon.
randall.. how much niacin and how often i'm wondering now.