HaPPy ThanksGiving -- 2009 --Eat Right -- SFB insights --AGW - Han Psor GENEs
randall
If your gonna get stuffed this thanksgiving then be sure
you eat those veggies high in sulforaphane, found in cruciferous
vegetables (cabbage, broccoli, broccoli sprouts, brussels sprouts,
cauliflower, cauliflower sprouts, bok choy, kale, collards, arugula,
kohlrabi, mustard, turnip, red radish and watercress).
Sulforaphane KNOCKs down LPS and downstream, or UP, dePending on how
you look at it, TNF and more flakes.
Really?
YeP LOOK:
www.ncbi.nlm.nih.gov/pubmed/19924513
Sulforaphane suppresses LPS-induced inflammation in primary rat
microglia.
Brandenburg LO, Kipp M, Lucius R, Pufe T, Wruck CJ.
Department of Anatomy and Cell Biology, RWTH Aachen University,
Wendlingweg 2, 52074, Aachen, Germany, lbrand...@ukaachen.de.
OBJECTIVE AND DESIGN: The aim of this study was to investigate the
signal transduction pathways involved in sulforaphane (SF) mediated
inhibition of the inflammatory response to lipopolysaccharide (LPS).
Additionally, we investigated the effects of SF and LPS on the
activity of Nrf2. MATERIAL: Primary rat microglia and the murine
microglia cell line BV2 were used. TREATMENT: Cells were treated with
LPS with or without SF. METHODS: Cell viability was measured via WST-
assay. Real-time RT-PCR was performed to analyze cytokine mRNA levels.
The nitric oxide (NO) release was measured in LPS-stimulated
microglia. The induction of various signal transduction pathways and
Nrf2 was determined by Western blotting. NF-kappaB and AP-1 activation
was measured by dual luciferase assay. RESULTS: We showed that SF
attenuates the LPS-induced increase of IL-1beta, IL-6, and TNF-alpha
expression in microglia. In addition, SF significantly decreases the
NO in a concentration-dependent manner. SF inhibits LPS-stimulated
ERK1/2 and JNK phosphorylation and thereby inhibits the LPS-induced
activation of NF-kappaB- and activator protein-1 (AP-1). Moreover, SF
and LPS together are able to induce Nrf2 activation. CONCLUSIONS: We
showed that SF, and also LPS by itself, are able to activate the
cell's defence against oxidative and electrophilic stress. We conclude
that SF could be a candidate agent for anti-inflammatory treatment of
the central nervous system.
PMID: 19924513
http://en.wikipedia.org/wiki/Sulforaphane
http://www.flaxhullignans.com/whatissulfo.php
[...]
Mechanism of Action
Sulforaphane's possible anticarcinogenic activity is accounted for by
its ability to induce phase II detoxication enzymes, such as
glutathione S-transferase and quinone reductase [NAD(P)H: (quinone-
acceptor) oxidoreductase]. These enzymes may afford protection against
certain carcinogens and other toxic electrophiles, including reactive
oxygen species.
<sniP>
=============
What AM i really thankful for this year?
Getting the answers mainly.
Auto and immunity is being revealed down to the core each and
every day.
So, i'm thankful for the dedicated scientists doing their WORK.
Since we learned this year that sFB's make Th17 which is the nemesis
to Treg's which turn off inflammation as is de rigueur, we now KNOW so
much MORE it's amazing.
So amazing that most folks don't KNOW or CARE. LOL
-------
This abstract from Littman et al really got things cooking.
www.ncbi.nlm.nih.gov/pubmed/19836068
Induction of intestinal Th17 cells by segmented filamentous bacteria
(SFB).
Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D,
Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda
K, Umesaki Y, Honda K, Littman DR.
Molecular Pathogenesis Program, The Kimmel Center for Biology and
Medicine of the Skirball Institute, New York University School of
Medicine, New York, NY 10016, USA.
The gastrointestinal tract of mammals is inhabited by hundreds of
distinct species of commensal microorganisms that exist in a
mutualistic relationship with the host. How commensal microbiota
influence the host immune system is poorly understood. We show here
that colonization of the small intestine of mice with a single
commensal microbe, segmented filamentous bacterium (SFB), is
sufficient to induce the appearance of CD4(+) T helper cells that
produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere
tightly to the surface of epithelial cells in the terminal ileum of
mice with Th17 cells but are absent from mice that have few Th17
cells. Colonization with SFB was correlated with increased expression
of genes associated with inflammation and antimicrobial defenses and
resulted in enhanced resistance to the intestinal pathogen Citrobacter
rodentium. Thus, manipulation of this commensal-regulated pathway may
provide new opportunities for enhancing mucosal immunity and treating
autoimmune disease.
PMID: 19836068
AND
www.ncbi.nlm.nih.gov/pubmed/19833089
Immunity. 2009 Oct 16;31(4):677-89.
The key role of segmented filamentous bacteria in the coordinated
maturation of gut helper T cell responses.
Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A,
Bridonneau C, Rochet V, Pisi A, De Paepe M, Brandi G, Eberl G, Snel J,
Kelly D, Cerf-Bensussan N.
INRA, U910, Unité Ecologie et Physiologie du Système Digestif, Domaine
de Vilvert, 78350 Jouy-en-Josas, France. valerie.gaboriau-
rout...@inserm.fr
Microbiota-induced cytokine responses participate in gut homeostasis,
but the cytokine balance at steady-state and the role of individual
bacterial species in setting the balance remain elusive. Herein,
systematic analysis of gnotobiotic mice indicated that colonization by
a whole mouse microbiota orchestrated a broad spectrum of
proinflammatory T helper 1 (Th1), Th17, and regulatory T cell
responses whereas most tested complex microbiota and individual
bacteria failed to efficiently stimulate intestinal T cell responses.
This function appeared the prerogative of a restricted number of
bacteria, the prototype of which is the segmented filamentous
bacterium, a nonculturable Clostridia-related species, which could
largely recapitulate the coordinated maturation of T cell responses
induced by the whole mouse microbiota. This bacterium, already known
as a potent inducer of mucosal IgA, likely plays a unique role in the
postnatal maturation of gut immune functions. Changes in the infant
flora may thus influence the development of host immune responses.
PMID: 19833089
http://en.wikipedia.org/wiki/Clostridium
And
www.ncbi.nlm.nih.gov/pubmed/19855381
Nat Immunol. 2009 Oct 22.
Enteric defensins are essential regulators of intestinal microbial
ecology.
Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjöberg J, Amir E,
Teggatz P, Barman M, Hayward M, Eastwood D, Stoel M, Zhou Y, Sodergren
E, Weinstock GM, Bevins CL, Williams CB, Bos NA.
[1] Division of Gastroenterology [2] Children's Research Institute,
Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Antimicrobial peptides are important effectors of innate immunity
throughout the plant and animal kingdoms. In the mammalian small
intestine, Paneth cell alpha-defensins are antimicrobial peptides that
contribute to host defense against enteric pathogens. To determine if
alpha-defensins also govern intestinal microbial ecology, we analyzed
the intestinal microbiota of mice expressing a human alpha-defensin
gene (DEFA5) and in mice lacking an enzyme required for the processing
of mouse alpha-defensins. In these complementary models, we detected
significant alpha-defensin-dependent changes in microbiota
composition, but not in total bacterial numbers. Furthermore, DEFA5-
expressing mice had striking losses of segmented filamentous bacteria
and fewer interleukin 17 (IL-17)-producing lamina propria T cells. Our
data ascribe a new homeostatic role to alpha-defensins in regulating
the makeup of the commensal microbiota.
PMID: 19855381
Of course we need defensins to protect us.
http://en.wikipedia.org/wiki/Defensins
And this brings us back to SFB's, Th17 (IL-17), antimicrobial peptides
via the lamina propria which hook up
with LL37 (LL-3) and the likely causation of psoriasis due to much
DEFA5 gene?
Sounds good but how accurate? LOL
http://en.wikipedia.org/wiki/DEFA5
Defensin-5 is a protein that in humans is encoded by the DEFA5 gene.[1]
[2]
Defensins are a family of microbicidal and cytotoxic peptides thought
to be involved in host defense. They are abundant in the granules of
neutrophils and also found in the epithelia of mucosal surfaces such
as those of the intestine, respiratory tract, urinary tract, and
vagina. Members of the defensin family are highly similar in protein
sequence and distinguished by a conserved cysteine motif. Several of
the alpha defensin genes appear to be clustered on chromosome 8. The
protein encoded by this gene, defensin, alpha 5, is highly expressed
in the secretory granules of ___Paneth__
___cells of the ___ileum___.[2]
--------
5 hits in pubmed for DEFA5
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=defa5&log$=activity
To recap:
http://en.wikipedia.org/wiki/Antimicrobial_peptides#Structure
[...]
Type: Linear cationic α-helical peptides
characteristic: lack in cysteine
AMPs : LL37 from humans
[...]
http://en.wikipedia.org/wiki/Antimicrobial_peptides#Immunomodulatory_Activities
[...]
Examples
Examples of antimicrobal peptides include magainins, alamethicin,
pexiganan or MSI-78, and other MSI peptides like MSI-843 and MSI-594,
polyphemusin, human antimicrobial peptide, LL-37, defensins and
protegrins.
<sniP>
-----------
Cathelicidin -- LL-37
http://en.wikipedia.org/wiki/LL-37
Cathelicidin antimicrobial peptide is a family of polypeptides found
in lysosomes in polymorphonuclear leukocytes (PMNs).[1]
<sniP>
-----------
Where is this MAYHAM haPPening?
Down under...
Huh?
Update on the ileocecal valve. The other white meat valve. LOL
It lives between your ileum and cecum:
http://en.wikipedia.org/wiki/Ileum
&
http://en.wikipedia.org/wiki/Cecum
The cecum or caecum (from the Latin caecus meaning blind) is a pouch,
connecting the ileum with the ascending colon of the large intestine.
It is separated from the ileum by the ileocecal valve (ICV) or
Bauhin's valve, and is considered to be the beginning of the large
intestine. It is also separated from the colon by the cecocolic
junction.
[...]
Etymology
The term cecum comes from the Latin caecum, literally "blind", here in
the sense "blind gut" or "cul de sac".
<snip>
http://en.wikipedia.org/wiki/Ileocecal_fold
Medical Dictionary: ileocecal valve
n.
The bilabial prominence of the terminal ileum into the large intestine
at the cecocolic junction in cadavers; it appears as a truncated cone
with a star-shaped orifice in the living. Also called ileocolic valve.
<snip>
Do you see the SFB hair ball?
http://www.gastrolab.net/ya056h.jpg
from the gastro lab folks rhymes with
http://www.gastrolab.net/pa-174.htm
OK, i'll stop fooling around. But this is the area where
SFB's GROW. Could this inflammation in the ileum be caused
by a lack of L. Plantarum in the colon?
Thusly my thesis in this 2002 post was correct and bacteria on either
side of the Ileocecal valve, influence the ratio of SFB's?
from:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_thread/thread/558ecc5807a93f39/504d84c96d45f6ea?hl=en&lnk=gst&q=ileocecal+valve+#504d84c96d45f6ea
And we now have 85 hits for sFB in the P NG:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=sfb+&qt_g=Search+this+group
Let's study the terrain.
http://www.gastro.com/Gastro/photography/ileocecal_valve.aspx
Side view of Ileum which empties into the cecum (large intestine)
http://www.sjhsyr.org/sjhhc/hidc07/graphics/images/en/19221.jpg
or
http://www.fotosearch.com/bigcomp.asp?path=LIF/LIF145/PED06020.jpg
http://www.nlm.nih.gov/medlineplus/ency/imagepages/19293.htm
The inflammation of Crohn's disease is nearly always found in the
ileocecal region. The ileocecal region consists of the last few inches
of the small intestine (the ileum), which moves digesting food to the
beginning portion of the large intestine (the cecum). However, Crohn's
disease can occur anywhere along the digestive tract.
<sniP>
Is this why psoriasis and crohn's are so related by excess Th17
produced
by an inflamed ileum?
from: (that 2002 article with that picture link-- above of the ileum)
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_thread/thread/558ecc5807a93f39/504d84c96d45f6ea?hl=en&lnk=gst&q=ileocecal+valve+#504d84c96d45f6ea
-----
OK, so that's something to be thankful for.
And i am. :)
===========
The fat is in the fire.
Let's chew it instead?
OK..
Just saw this cool lipids and inflammation slide show from my 2002
post or
thread.
Forgot how much I relished it back them. Still do today:
Role of Lipoproteins in Inflammation (Philip Barter, MD, PhD)
http://www.lipidsonline.org/slides/slide01.cfm?tk=18&dpg=1
============
Let's talk about the weather instead?
James Hansen says the weather is going to kill us. WE have time to
do something but he doesn't say what. Obama will tax us to do that
something. But shouldn't we be building nuclear generators?
http://solveclimate.com/blog/20091123/tipping-points-melting-ice-rising-oceans
Tipping Points: Melting Ice, Rising Oceans
by James Hansen - Nov 23rd, 2009
<sniP>
12 Facts about Global Climate Change that You Won't Read in the
Popular Press
http://www.webcommentary.com/php/ShowArticle.php?id=daleoj&date=090905
James E. Hansen: The "Bernie Madoff" of Climate Science?
http://www.webcommentary.com/php/ShowArticle.php?id=websterb&date=091124
Al Gore is laughing all the way to the BANK with BILLIONs of carbon
bucks?
http://blog.nj.com/njv_paul_mulshine/2009/11/clouds_hang_over_the_global-wa.html
[...]
The alarmists harp on that infinitesimal increase, he says, while they
ignore the most prevalent greenhouse gas of them all — water vapor.
Clouds reflect sunlight back into the sky. And that is at the center
of a developing dispute among scientists. Easterbrook is on the side
of a Danish scientist named Henrik Svensmark. In the 1990s, Svensmark
developed a theory that links cloud formation to sunspots. When the
number of sunspots is low, more cosmic rays get through to the
atmosphere. And these rays, Svensmark theorizes, are the primary cause
of cloud formation. The clouds reflect more sunlight back into space.
Earth gets colder.
<sniP>
Is Svensmark RIGHT and all the AGW proponents WRONG?
http://www.spectator.co.uk/coffeehouse/5564578/is-the-world-cooling-or-not-and-what-is-to-blame.thtml
Is the world cooling or not – and what is to blame?
Daniel Korski 4:18pm
The Financial Times supplement this weekend contained profiles of the
world’s leading climate experts, including - the magazine promised -
the world’s leading sceptic. I quickly leafed through the pages to see
who had been picked as the whipping boy, expecting to see a Danish
name. No, not that of Bjørn Lomborg, who became (in)famous for his
book The Sceptical Environmentalist, but that of Professor Henrik
Svensmark. In the end, it was Richard Lindzen.
But it is Svensmark’s research that may prove the greatest challenge
to the prevailing consensus on climate dynamics. The Danish scientist,
author of The Chilling Stars, become noted because of his research
into cosmic rays and their effect on cloud formation. His theories
contradict the IPCC’s theory of anthropogenic global warming, which
basically blames last century's rise in average global temperature on
human CO2 emissions. Instead, Svensmark hypothesises that clouds
created by cosmic rays, which are in part controlled by the activity
of the sun, regulate the Earth's climate. Because this contradicts the
IPCC's view of global warming, Svensmark's theory has been ignored by
the climate alarmists and the scientist himself vilified.
There have also been some more sober counterarguments - including by
the British scientist Mike Lockwood, who argued in 2007 that, even if
the sun influenced climate change in the past, it could not possibly
be responsible for recent changes.
But new research now seems to be backing up Svensmark’s theory. Dr.
Svensmark and his team undertook an elaborate laboratory experiment in
a reaction chamber the size of a small room. The team duplicated the
chemistry of the lower atmosphere by injecting the gases found there
in the same proportions, and adding ultraviolet rays to mimic the
actions of the sun.
Result: a huge number of floating microscopic droplets quickly filled
the chamber. These were super-small clusters of sulphuric acid and
water molecules – which are the building blocks for cloud condensation
nuclei - that had been catalysed by the electrons released by cosmic
rays.
The point? The research experimentally identified a causal mechanism
by which cosmic rays can facilitate the production of clouds in
Earth's atmosphere. This does not disprove the existence of greenhouse
gases and the greenhouse effect. But it does challenge the “man-only”
theory, and suggests that the IPCC should consider the effect of
cosmic particles in examining climate dynamics. Or, at least, accept
that there is a long way to go before we fully understand climate
dynamics and who plays what role.
----
Read TrevorsDen comment:
**'Climategate'
The cat is out of the bag. The IPCC 'science' is bigoted junk.
This study of the code used by Hadley CRU proves the scam.
What is the code to this science caPer?
http://wattsupwiththat.com/2009/11/22/cru-emails-may-be-open-to-interpretation-but-commented-code-by-the-programmer-tells-the-real-story/
CRU Emails “may” be open to interpretation, but commented code by the
programmer tells the real story
<sniP>
Then TrevorsDen says:
**It clearly shows data is manipulated to avoid showing declines in
temperatures**
Next TrevorsDen says:
**Lord Lawson has set up a new think tank ...
...the Global Warming Policy Foundation (www.thegwpf.org) ...
... to open up the debate on 'global warming'.
http://www.timesonline.co.uk/tol/comment/columnists/ **
===========================
OK, one more psor thing and i'm DONE.
http://www.eurekalert.org/pub_releases/2009-11/afst-fm112309.php
First 'genetic map' of Han Chinese may aid search for disease
susceptibility genes
Genome Institute of Singapore researchers compiled map based on genome-
wide variations of 6,000 samples
The first genetic historical map of the Han Chinese, the largest
ethnic population in the world, as they migrated from south to north
over evolutionary time. was published online today by the American
Journal of Human Genetics by scientists at the Genome Institute of
Singapore (GIS).
Based on genome-wide DNA variation information in over 6,000 Han
Chinese samples from 10 provinces in China, this new map provides
information about the population structure and evolutionary history of
this group of people that can help scientists to identify subtle
differences in the genetic diversity of Asian populations.
Understanding these differences may aid in the design and
interpretation of studies to identify genes that confer susceptibility
to such common diseases as diabetes in ethnic Chinese individuals.
Understanding these differences also is crucial in exploring how genes
and environment interact to cause diseases.
With the genetic map, the GIS scientists were able to show that the
northern inhabitants of China were genetically distinguishable from
those in the south, a finding that seems very consistent with the Han
Chinese's historical migration pattern.
The genetic map also revealed that the genetic divergence was closely
correlated with the geographic map of China. This finding suggests the
persistence of local co-ancestry in the country.
"The genome-wide genetic variation study is a powerful tool which may
be used to infer a person's ancestral origin and to study population
relationships," said Liu Jianjun, Ph.D., GIS Human Genetics Group
Leader.
"For example, an ethnic Chinese born and bred in Singapore can still
be traced back to his or her ancestral roots in China," Dr. Liu said.
"By investigating the genome-wide DNA variation, we can determine
whether an anonymous person is a Chinese, what the ancestral origin of
this person in China may be, and sometimes which dialect group of the
Han Chinese this person may belong to.
"More importantly, our study provides information for a better design
of genetic studies in the search for genes that confer susceptibility
to various diseases," he added.
Of particular interest to people in Singapore are the findings that
while the majority of Singaporean Chinese hail from Southern China as
expected, some have a more northern ancestral origin.
GIS Executive Director Edison Liu, M.D., said, "Genome association
studies have provided significant insights into the genes involved in
common disorders such as diabetes, high cholesterol, allergies, and
neurological disorders, but most of this work has been done on
Caucasian populations.
"More recently, Dr. Liu Jianjun from our institute has been working
with his Chinese colleagues to define the genetic causes of some of
these diseases in Asian populations," the GIS Executive Director
added. "This work refined those tools so that the results will not be
obscured by subtle differences in the genetic diversity of Asian
populations. In the process, Dr. Liu has reconstructed a genetic
historical map of the Chinese people as they migrated from south to
north over evolutionary time."
"There are definite differences in genetic architecture between
populations," noted Chia Kee Seng, M.D., Head, Department of
Epidemiology & Public Health, National University of Singapore (NUS),
and Director, NUS-GIS Centre for Molecular Epidemiology.
"We have seen this in the Singapore Genome Variation Project, a Joint
NUH-GIS effort. Understanding these differences is crucial in
exploring how genes and environment interact to cause diseases," he
added.
The research results published in American Journal of Human Genetics
is part of a larger ongoing project on the genome-wide association
study of diseases among the Chinese population. The project is a
collaboration between GIS and several institutions and universities in
China.
In Jan. 2009, Nature Genetics published the findings of researchers at
the GIS and Anhui Medical University, China, on psoriasis, a common
chronic skin disease. In that study, led by Dr. Liu Jianjun at the GIS
and Dr. Zhang Xuejun at the Anhui Medical University, the scientists
discovered a genetic variant that provides protection against the
development of psoriasis. The collaboration's recent discovery of over
a dozen genetic risk variants for systematic lupus erythematosus (SLE)
in the Chinese population was published in Nature Genetics in Oct.
2009.
###
The American Journal of Human Genetics paper is titled, "Genetic
Structure of the Han Chinese Population Revealed by Genome-wide SNP
Variation."
Authors: Jieming Chen 1*, Houfeng Zheng 3,4,5*, Jin-Xin Bei 6,7,
Liangdan Sun 3,4 5, Wei-hua Jia 6,7, Tao Li 8,9, Furen Zhang 10, Mark
Seielstad 1,2,11, Yi-Xin Zeng 6,7, Xuejun Zhang 3,4 5, Jianjun Liu
1,2,3,4
==================
randall.... the psor and talking about the weather post..
zzznot
but it's not like I see dramatic effects.
J.
"randall" <ranh...@aol.com> wrote in message
news:445293b5-5c03-4a9b...@r24g2000yqd.googlegroups.com...
randall
> I dunno, I do try to eat my cruciferous veggies,
> but it's not like I see dramatic effects.
>
> J.
>
>
> news:445293b5-5c03-4a9b...@r24g2000yqd.googlegroups.com...
> Hi,
>
> If your gonna get stuffed this thanksgiving then be sure
> you eat those veggies high in sulforaphane, found in cruciferous
> vegetables (cabbage, broccoli, broccoli sprouts, brussels sprouts,
> cauliflower, cauliflower sprouts, bok choy, kale, collards, arugula,
> kohlrabi, mustard, turnip, red radish and watercress).
>
> Sulforaphane KNOCKs down LPS and downstream, or UP, dePending on how
> you look at it, TNF and more flakes.
>
> Really?
JRS,
I recall i did need to be rather psor-severe to see the broccoli
cruciferous veggie (CV'ss) difference.
Then....
Seemingly like a halo of healing of a few percent that lasted
a few days at best after eating broccoli....
Like your curry experience i'm SURE. LOL
Then again it could have been NAC from CV's which you know how i feel
about that glutathione precusor.
http://en.wikipedia.org/wiki/Acetylcysteine
Over 300 hits for : me + nac with psoriasis in the groups:
http://groups.google.com/groups/search?hl=en&q=nac+psoriasis+randall&sitesearch=
Yet i posted an abstract for LPS and sulforaphane and found more in
the same vein.
SO that means sulforaphane is in the skin GAME and LPS is to BLAME
for some percentage (PASi) and perhaPs GENETIC pathway action as
WELL.
SO?
Then if you WANT to control your genes, maybe you can via your
enviroment and what you
stuff in your face.
Certainly argues for you to go with the sweet whey and if your nascent
good flora (biofilm)
levels are still existent then your gonna clear some NICE percentage
of PASi i'd wager.
OK....
Bottom line on ___minerals___ comes to mind if your LACTi loving FLORA
and colon is slightly acidic and that
pathway isn't DEAD and causing an alkaline colon and sFB blowback in
to your ileum
from the cecum? And causing excess Th17 which you didn't seem to hook
uP with. LOL
Still i'd lay ODDs on excess Th17 via SFB;s and no amount of CV's is
gonna TRUMp that. ;~/
SFB + ME in the P NG: 86 hits
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=SFB+randall+psoriasis
How many of those have the kicker L. Plantarum?
Only 16:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=SFB+randall+psoriasis+plantarum
Back to the elemental magnesium.
You might need more magnesium. It also actually beats down
inflammation via LPS/TNF pathways in
conjunction against the calcium pathway and surely would help with NAC
& sulforaphane et al in
those cruciferous veggies (CV's). And maybe it reins in excess
calcium that goes ALL calmodulin like?
http://en.wikipedia.org/wiki/Calmodulin
http://en.wikipedia.org/wiki/Ca2%2B/calmodulin-dependent_protein_kinase
Ok, back to mg:
www.ncbi.nlm.nih.gov/pubmed/19933511
[...]
MgSO(4) significantly inhibited endotoxin-induced up-regulation of
inflammatory molecules and NF-kappaB activation in activated RAW264.7
cells. The effects of MgSO(4) on inflammatory molecules and NF-kappaB
may involve antagonizing calcium, inhibiting the L-type calcium
channels, or both.
PMID: 19933511
And of course it acts when YOUR levels are low to begin with.
www.ncbi.nlm.nih.gov/pubmed/19658279
And like sulforaphane it's another way to further manipulate LPS/TNF
attentuation and acts like a tag team.
http://en.wikipedia.org/wiki/Magnesium#Biological_role
And
Just like our prez, while he looks cool and talks kewl, he's really
feeding the hoi polloi pablum while he raids the till for his shills
and
this means his magnesium and BUCK bottom line must be suspect. LOL
Why?
Because even he can't stop his HAIR from turning white. LOL
Why? .... is he scarred?
And with the $ bubble he's in super duPer CARTER level trouble.
The Dollar Bubble: (nearly 60 minutes) Buy GOLD and Silver but load
up on magnesium for your health. <G>
http://www.youtube.com/watch?v=eZA0qNsf4m0
aND JUST LIKE THe inverse of a collapsing DOLLAR WE HAVE TO KNOCK DOWN
LPS AND TNF by raising magnesium. <w>
YOU don't want to BUY the dePression of the heartbreak due to low
minerals?
Buy silver and gold. LOL
Sorry silly political segue. :)
Here are two pertinent abstracts:
www.ncbi.nlm.nih.gov/pubmed/16180088
Intestinal and cardiac inflammatory response shows enhanced endotoxin
receptor (CD14) expression in magnesium deficiency.
Chmielinska JJ, Tejero-Taldo MI, Mak IT, Weglicki WB.
Division of Experimental Medicine, Department of Biochemistry and
Molecular Biology, USA. phy...@gwumc.edu
Substance P is elevated in plasma and in other tissues during Mg-
deficiency, and was found localised to neuronal C-fibres of cardiac
and intestinal tissues, where it could promote neurogenic
inflammation. Plasma prostaglandin E2 (PGE2), indicative of systemic
inflammation, rose significantly (>or=4 fold, p<0.01) after 1 week and
remained elevated through week 2 and 3 in rat on the Mg-deficient
(MgD) diet. Concomitantly, total blood glutathione decreased by 50%.
Immunohistochemical staining for endotoxin (lipopolysaccaride, LPS)
receptor, CD14 was prominent in macrophage-type cells in intestinal
tissue; more importantly, cardiac tissue revealed both CD11b (monocyte/
macrophage surface protein) and CD14 positive cells after 3 weeks in
rats on MgD diet. Western blot analysis indicated a significant
increase in the endotoxin receptor protein level in the 3 week MgD
hearts. Since CD14 is known to be up-regulated in cells exposed to
LPS, these observations suggest that prolonged Mg-deficiency results
in increased intestinal permeability to bacterial products that induce
the endotoxin receptor in cells localized to myocardial and intestinal
tissues. These CD14 positive cells may amplify the cardiomyopathic
inflammatory process by stimulating TNF-alpha and other pro-
inflammatory cytokines.
PMID: 16180088
www.ncbi.nlm.nih.gov/pubmed/19933155
TNF{alpha} shedding and epidermal inflammation are controlled by Jun
proteins.
Guinea-Viniegra J, Zenz R, Scheuch H, Hnisz D, Holcmann M, Bakiri L,
Schonthaler HB, Sibilia M, Wagner EF.
Cancer Cell Biology Programme, Centro Nacional de Investigaciones,
Oncológicas (CNIO), E-28029 Madrid, Spain;
Inducible epidermal deletion of JunB and c-Jun in adult mice causes a
psoriasis-like inflammatory skin disease. Increased levels of the
proinflammatory cytokine TNFalpha play a major role in this phenotype.
Here we define the underlying molecular mechanism using genetic mouse
models. We show that Jun proteins control TNFalpha shedding in the
epidermis by direct transcriptional activation of tissue inhibitor of
metalloproteinase-3 (TIMP-3), an inhibitor of the TNFalpha-converting
enzyme (TACE). TIMP-3 is down-regulated and TACE activity is
specifically increased, leading to massive, cell-autonomous TNFalpha
shedding upon loss of both JunB and c-Jun. Consequently, a prominent
TNFalpha-dependent cytokine cascade is initiated in the epidermis,
inducing severe skin inflammation and perinatal death of newborns from
exhaustion of energy reservoirs such as glycogen and lipids.
Importantly, this metabolic "cachectic" phenotype can be genetically
rescued in a TNFR1-deficient background or by epidermis-specific re-
expression of TIMP-3. These findings reveal that Jun proteins are
essential physiological regulators of TNFalpha shedding by controlling
the TIMP-3/TACE pathway. This novel mechanism describing how Jun
proteins control skin inflammation offers potential targets for the
treatment of skin pathologies associated with increased TNFalpha
levels.
PMID: 19933155
WE have big time C-JUN in the p ng:
http://groups.google.com/groups/search?hl=en&q=c-jun+psoriasis+randall&sitesearch=
c-jun + c-fos = ap1
http://en.wikipedia.org/wiki/AP-1_(transcription_factor)
activator protein 1 (AP-1) is a transcription factor which is a
heterodimeric protein composed of proteins belonging to the c-Fos, c-
Jun, ATF and JDP families. It regulates gene expression in response to
a variety of stimuli, including cytokines, growth factors, stress, and
bacterial and viral infections. AP-1 in turn controls a number of
cellular processes including differentiation, proliferation, and
apoptosis.
<sniP>
I should read the one that says c-jun and GLOOM. LOL
Or only those with leucine ziPPer in them?
http://en.wikipedia.org/wiki/Leucine_zipper
As ap1 and leucine zipper are involved with
http://en.wikipedia.org/wiki/Gene_expression
So much for going off course but makes the GENETIC point.
OK, let's do the layman version of why magnesium is so swell.
http://www.wellnessresources.com/health/articles/magnesium_the_anti-inflammatory_mineral
Magnesium – The Anti-Inflammatory Mineral
Tuesday, November 24, 2009 - Byron Richards, CCN
A new study of 3,713 postmenopausal women shows that magnesium is a
powerful anti-inflammatory nutrient. Each 100 mg of magnesium per day
was associated with a significant reduction in various inflammatory
markers.
Magnesium is the most lacking mineral in the human diet. This is due
primarily to Big Agribusiness farming practices that have stripped our
soils of vital minerals needed for human health. It is complicated by
processed diets lacking in magnesium-containing fresh fruits and
vegetables. When you consider that inflammation is behind almost all
health problems the consequence of eating a magnesium deficient diet
becomes obvious.
The study showed that inflammatory markers such as CRP (C-reactive
protein), TNFa (tumor necrosis factor alpha), and IL6 (interleukin 6)
were all reduced when magnesium intake was higher. These are common
inflammatory markers that are often elevated with the diseases of
aging.
Furthermore, various inflammatory markers relating to the walls of
arteries were also reduced when magnesium was adequate. Inflammation
on the lining of the arteries is required for plaque formation.
Reducing such inflammation is highly protective to arterial health.
It is not a stretch to say that if public health officials did nothing
other than ensure vitamin D and magnesium sufficiency the entire
health of a nation would be drastically improved and health care costs
would be significantly lower.
-------------
More from Bryon Richards on MAG:
http://www.wellnessresources.com/health/articles/magnesium_fiber_reduce_diabetes_risk/
Magnesium & Fiber Reduce Diabetes Risk, 11/25/2009
A Hawaiian study followed 75,512 men and women for 8 years tracking
their fiber intake, magnesium intake, and the glycemic load of their
diets to see who developed diabetes
<sniP>
http://www.wellnessresources.com/health/articles/magnesium_deficiency_sets_the_stage_for_plaque_in_the_arteries/
Magnesium Deficiency Sets the Stage for Plaque in the Arteries,
11/26/2009
A new animal study shows that low levels of magnesium promotes plaque
formation in the arteries. During the study period magnesium deficient
animals developed significantly more plaque in their aortas.
<sniP>
http://www.wellnessresources.com/health/articles/selenium_and_iodine_are_needed_to_protect_your_thyroid_gland/
Selenium and Iodine are Needed to Protect Your Thyroid Gland,
11/23/2009
A lack of selenium or iodine exposes your thyroid to unnecessary
damage from chemicals, according to a new study testing the adverse
effects of a common mosquito insecticide.
<sniP>
==========
Big mac's pump out more inflammation in a LOW magnesium enviroment.
What?
Yikes... lol
http://en.wikipedia.org/wiki/Macrophage
A BIG eater and white cell. <w>
www.ncbi.nlm.nih.gov/pubmed/12892381
Enhanced release of IL-1beta and TNF-alpha following endotoxin
challenge from rat alveolar macrophages cultured in low-mg(2+) medium.
Shogi T, Miyamoto A, Ishiguro S, Nishio A.
Department of Veterinary Pharmacology, Faculty of Agriculture,
Kagoshima University, 1 - 21-24 Korimoto, Kagoshima 890-0065, Japan.
Our previous data have demonstrated that LPS-stimulated alveolar
macrophages produce higher levels of IL-1beta and TNF-alpha mRNA in
low-Mg(2+) medium than in normal-Mg(2+) medium. In this study, we
examined whether the increased mRNA levels are correlated with the
release of both cytokines. LPS-stimulated alveolar macrophages
released higher amounts of IL-1beta and TNF-alpha in low-Mg(2+) medium
than in normal-Mg(2+) medium. The enhanced release of IL-1beta was
completely suppressed by pretreatment with verapamil (a calcium entry
blocker), U73122 (a phospholipase C inhibitor), W-7 (a calmodulin
inhibitor), and curcumin (an activator-protein [AP]-1 inhibitor), and
weakly suppressed by dexamethasone (which inhibits nuclear factor [NF]-
kappaB and AP-1). On the other hand, the enhanced release of TNF-alpha
was completely suppressed by U73122, and strongly suppressed by TMB-8
(which inhibits calcium release from the endoplasmic reticulum) and
W-7, and weakly suppressed by pyrrolidine dithiocarbamate (a NF-kappaB
inhibitor). From these results, we conclude that the enhanced release
of IL-1beta and TNF-alpha from LPS-stimulated alveolar macrophages in
low-Mg(2+) medium depends partly on the enhanced synthesis of both
cytokines, and occurs partly via identical, and partly via different,
signaling pathways.
PMID: 12892381
Maybe magnesium doesn't like the lung Big Mac's? Or it's the
pathways? Will check gateway links for pathways.
And
Will bring it here and see what's new for this month too?
OK..
OK, now that i've got you all pumped to go crazy on magnesium recall
what
happens with to much of a good thing (milk of magnesia) :
http://acmeglobal.com/AcmeLabs/Products/Human/ProdPics/Milk-Magnesia.jpg
==============
OK, so how does glutathione come in to focus with sulphoraphane/
magnesium and more?
Easy.... it's the DETOX vitamin and liver helper.... While mothers
little helper is excess acetaminophen
it dePletes glutahione and that's a HUgE negative that i've fingered
for autism pathways.
The folks at Stanford brought that to my attention.
And here's another one of those nice studies to look at in the news.
http://www.sciencedaily.com/releases/2009/11/091117184535.htm
Common Herbal Medicine May Prevent Acetaminophen-Related Liver Damage,
Says Researcher
ScienceDaily (Nov. 18, 2009) — A well-known Eastern medicine
supplement may help avoid the most common cause of liver
transplantation, according to a study by researchers at the Stanford
University School of Medicine. The finding came as a surprise to the
scientists, who used a number of advanced genetic and genomic
techniques in mice to identify a molecular pathway that counters
acetaminophen toxicity, which leads to liver failure.
"I didn't know anything about the substance that was necessary for the
pathway's function, so I had to look it up," said Gary Peltz, MD, PhD,
professor of anesthesiology. "My postdoctoral fellow, whose parents
and other family members in Asia were taking this compound in their
supplements, started laughing. He recognized it immediately."
The molecule was S-methylmethionine, which had been marketed as an
herbal medicine known as Vitamin U for treatment of the digestive
system. It is highly abundant in many plants, including cabbage and
wheat, and is routinely ingested by people. Coincidentally, Garnett
Cheney, MD, at Stanford University performed a series of studies in
the 1950s in which he used the compound to treat peptic ulcers.
Peltz is the senior author of the research, which will be published
online Nov. 18 in Genome Research. The experiments were conducted in
Peltz's laboratory at Roche Palo Alto in Palo Alto, Calif., where
Peltz worked before coming to Stanford in July 2008. He is continuing
the research at Stanford. The first author of the paper, Hong-Hsing
Liu, MD, PhD, is now a postdoctoral scholar in Peltz's Stanford lab.
_____Acetaminophen_____ is a pain reliever present in many over-the-
counter cold and flu medicines. It is broken down, or metabolized, in
the body into byproducts -- one of which can be very toxic to the
liver. At normal, therapeutic levels, this byproduct is easily
deactivated when it binds to a naturally occurring, protective
molecule called glutathione. But the body's glutathione stores are
finite, and are quickly depleted when the recommended doses of
acetaminophen are exceeded.
Unfortunately, the prevalence of acetaminophen makes it easy to
accidentally exceed the recommended levels, which can occur by dosing
more frequently than indicated or by combining two or more
acetaminophen-containing products. However, severe liver damage can
occur at even two to three times the recommended dose (the maximum
adult dose is 4 grams per day; toxic daily levels range from 7 to 10
grams).
"It's a huge public health problem," said Peltz. "It's particularly
difficult for parents, who may not realize that acetaminophen is in so
many pediatric medicines." Acetaminophen overdose is the most common
cause of liver transplantation in this country. The only effective
antidote is an unpalatable compound called NAC that can induce nausea
and vomiting, and must be administered as soon as possible after the
overdose.
Peltz and his colleagues used 16 inbred strains of laboratory mice for
their investigations. Most strains are susceptible to acetaminophen
toxicity, but one is resistant. They compared how the drug is
metabolized by the different strains and looked for variations in gene
expression and changes in endogenous metabolites in response to
acetaminophen administration. They identified 224 candidate genes that
might explain the resistant strain's ability to ward off liver damage,
and then plumbed computer databases to identify those involved in
metabolizing acetaminophen's dangerous byproducts.
One, an enzyme called Bhmt2, fit the bill: It helped generate more
glutathione, and its sequence varied between the resistant and non-
resistant strains of mice. Bhmt2 works by converting the diet-derived
molecule S-methylmethionine, or SMM, into methionine, which is
subsequently converted in a series of steps into glutathione. The
researchers confirmed the importance of the pathway by showing that
SMM conferred protection against acetaminophen-induced liver toxicity
only in strains of mice in which the Bhmt2 pathway was functional.
"By administering SMM, which is found in every flowering plant and
vegetable, we were able to prevent a lot of the drug's toxic effect,"
said Peltz. He and his colleagues are now working to set up clinical
trials at Stanford to see whether it will have a similar effect in
humans. In the meantime, though, he cautions against assuming that
dosing oneself with SMM will protect against acetaminophen overdose.
"There are many pathways involved in the metabolism of this drug, and
individuals' genetic backgrounds are tremendously variable. This is
just one piece of the puzzle; we don't have the full answer," he said.
However, if subsequent studies are promising, Peltz envisions possibly
a co-formulated drug containing both acetaminophen and SMM or using
SMM as a routine dietary supplement.
----
Their abstract:
www.ncbi.nlm.nih.gov/pubmed/19923254
An integrative genomic analysis identifies Bhmt2 as a diet-dependent
genetic factor protecting against acetaminophen-induced liver
toxicity.
Liu HH, Lu P, Guo Y, Farrell E, Zhang X, Zheng M, Bosano B, Zhang Z,
Allard J, Liao G, Fu S, Chen J, Dolim K, Kuroda A, Usuka J, Cheng J,
Tao W, Welch K, Liu Y, Pease J, de Keczer SA, Masjedizadeh M, Hu JS,
Weller P, Garrow T, Peltz G.
Department of Genetics and Genomics, Roche Palo Alto, Palo Alto,
California 94304, USA;
Acetaminophen-induced liver toxicity is the most frequent
precipitating cause of acute liver failure and liver transplant, but
contemporary medical practice has mainly focused on patient management
after a liver injury has been induced. An integrative genetic,
transcriptional, and two-dimensional NMR-based metabolomic analysis
performed using multiple inbred mouse strains, along with knowledge-
based filtering of these data, identified betaine-homocysteine
methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that
affected susceptibility to acetaminophen-induced liver toxicity in
mice. Through an effect on methionine and glutathione biosynthesis,
Bhmt2 could utilize its substrate (S-methylmethionine [SMM]) to confer
protection against acetaminophen-induced injury in vivo. Since SMM is
only synthesized in plants, Bhmt2 exerts its beneficial effect in a
diet-dependent manner. Identification of Bhmt2 and the affected
biosynthetic pathway demonstrates how a novel method of integrative
genomic analysis in mice can provide a unique and clinically
applicable approach to a major public health problem.
PMID: 19923254
Do you need proper diet and to get ON the TREADMILL to get off the
cancer lifestyle?
www.ncbi.nlm.nih.gov/pubmed/18342145
But back to my inclination for NAC and raised glutathione
DETOXification pathways.
Would autistic children or adults benefit from high NAC levels and a
Bhmt2 agonist with
a side order of s-methylmethionine?
You betcha....provided they have homeostatic levels of iodine,
selenium and those
other minerals i'm not gonna mention in this short little post. LOL
----------
I've had seven hits for nac + glutathione + autism + stanford:
http://groups.google.com/groups/search?hl=en&qt_s=1&q=randall+stanford+autism+nac+glutathione
So JR maybe the lack of glutathione via genetic variant or snp for
Bhmt2 is whats particularly salient for
low glutathione and the inability of detox level II enzmes in the
liver?
http://en.wikipedia.org/wiki/Betaine-homocysteine_methyltransferase
Betaine-homocysteine methyltransferase is a zinc metallo-enzyme that
catalyzes the transfer of a methyl group from betaine to homocysteine
to produce dimethylglycine and methionine respectively:[1]
betaine + homocysteine → dimethylglycine + methionine
Methionine in turn can donate the methyl group to methylate DNA,
proteins, lipids, and other intracellular metabolites.
Isozymes
In humans, there are two isozymes, BHMT[2][3] and BHMT2,[4][5] each
encoded by a separate gene.
Tissue distribution
BHMT is expressed most predominantly in the liver and kidney.[6]
Clinical significance
Anomalies in homocysteine metabolism have been implicated in disorders
ranging from vascular disease to neural tube birth defects such as
spina bifida.
<sniP>
And improper conversion of methionine can lead to atherosclerosis..
Yikes
That heart attack is more common for psoriatics. So low methionine and
magnesium?
http://en.wikipedia.org/wiki/Methionine
S-methylmethionine
http://en.wikipedia.org/wiki/Methylmethionine
Whoever wrote that science article must have visited the last link.
LOL
Busted...
But so?
I do it all the time.
And as Newton said: He could oNLY see so FAR standing on the BACKs of
Giants. <G>
=====================
As genes and pathways come in to focus.
Please use gateway links from UCSD for precise up to date pathway
insights:
http://links.gateways.nature.com/
2009 november
http://www.signaling-gateway.org/update/featured/index.html
Lipid signaling: LPA's ways of actin
Lysophosphatidic acid (LPA) controls actin dynamics indirectly,
through cell surface receptor-mediated signaling, and directly, by
binding and inhibiting villin.
Rearrangement of the actin cytoskeleton is crucial for the control of
cell morphology and migration. Actin-binding proteins regulate the
polymerization of actin into filaments, and the cross-linking of these
into bundles. LPA is known to induce cytoskeletal rearrangements, but
the mechanisms involved are not well understood. Now, two studies in
the Journal of Biological Chemistry show how LPA can influence actin
dynamics in different ways. First, Masayuki Masu and colleagues report
that in mouse embryos, extracellular LPA controls phosphorylation of
an actin binding protein through a cell surface receptor and Rho
GTPase signaling cascade, leading to the formation of specialized
lysosomes. Meanwhile, Seema Khurana and colleagues used in vitro
methods to show that LPA and phosphatidylinositol 4,5-bisphosphate
(PIP2) compete for binding sites in villin, an actin binding protein,
with opposing effects on actin reorganization.
Extracellular LPA (see the Lipid of the month) is produced by the
secreted enzyme autotaxin, which is encoded by the Enpp2 gene. Defects
including failures in yolk sac angiogenesis kill Enpp2-/- mouse
embryos before birth, but the cellular mechanisms involved are not
well understood. Masu and colleagues used a whole embryo culture
system to probe the role of autotaxin–LPA in specialized yolk sac
cells. These visceral endoderm (VE) cells usually have distinctively
large lysosomes, but these were fragmented in VE cells from Enpp2-/-
embryos.
Using pharmacological inhibitors and electroporation of dominant-
negative constructs, the authors showed that the formation of large
lysosomes in VE cells requires LPA receptor signaling, Rho GTPase, the
kinase ROCK, and the downstream LIM kinase (LIMK). Cofilin, an actin
binding protein that stimulates filament disassembly, is
phosphorylated and inactivated by LIMK. The steady-state levels of
cofilin phosphorylation were significantly decreased in Enpp2-/- VE
cells, and this correlated with a decrease in polymerized actin.
Culturing the embryos with compounds to either disrupt or stabilize
actin filaments confirmed that actin polymerization is involved in VE
lysosome formation, and that dynamic regulation of actin turnover is
required. Without autotaxin–LPA signaling to regulate cofilin, the
balance of actin polymerization is lost and the lysosomal defects
ensue.
Another actin-binding protein, villin, is specific to endothelial
cells, where it regulates actin dynamics, cell morphology and
migration. PIP2 is known to bind villin and modify its actin
regulatory functions. Khurana and colleagues found that LPA also binds
villin in vitro, and kinetic analysis revealed that villin has a
slightly higher affinity for LPA than for PIP2. On binding, neither
lipid induced global changes in the conformation of full-length
villin, but each had a different effect on the secondary structure of
villin peptides. This difference had functional consequences for full-
length villin; c-Src kinase was unable to phosphorylate the
recombinant protein whether PIP2 was present or absent, but it was
able to do so in the presence of LPA. In vitro, actin filaments are
cross-linked into bundles by villin, but this did not occur in the
presence of LPA. LPA also inhibited the actin capping function of
villin as well as its depolymerizing activity. PIP2, by contrast, only
inhibited the last function.
Whereas the study by Masu and colleagues identifies a pathway by which
extracellular LPA modifies the actin cytoskeleton, in vivo binding of
villin would involve intracellular LPA. The different cellular
membranes have distinct phospholipid compositions, suggesting that LPA
or PIP2 binding might regulate villin localization as well as
phosphorylation. Intracellular LPA production involves phospholipase
enzymes, not autotaxin, and is more tightly regulated than
extracellular production, although it is not certain that the two LPA
pools are entirely separate. Nevertheless, control of actin dynamics
from inside or outside the cell could be critical for many of the
pathological functions of LPA.
Emma Leah
Lipidomics Gateway
References:
Koike, S., Keino-Masu, K., Ohto, T., Sugiyama, F., Takahashi, S. &
Masu, M.
Autotaxin/lysophospholipase D-mediated LPA signaling is required to
form distinctive large lysosomes in the visceral endoderm cells of the
mouse yolk Sac
J. Biol. Chem. published online 5 October 2009 (DOI: 10.1074/
jbc.M109.012716)
==============
I love these UcSD people... their dedication is 100% and the ones that
stay
close to home are in a beautiful locale.
randall.. eating his curds/whey and cruciferous veggies with extra
magnesium
JRStern
wrote:
>Then again it could have been NAC from CV's which you know how i feel
>about that glutathione precusor.
could be, but if the cv's don't do it, then what?
>Still i'd lay ODDs on excess Th17 via SFB;s and no amount of CV's is
>gonna TRUMp that. ;~/
well then if and when the cvs do work, if not on the th17, then how do
they work?
>Back to the elemental magnesium.
almonds.
>"There are many pathways involved in the metabolism of this drug, and
>individuals' genetic backgrounds are tremendously variable. This is
>just one piece of the puzzle; we don't have the full answer," he said.
>However, if subsequent studies are promising, Peltz envisions possibly
>a co-formulated drug containing both acetaminophen and SMM or using
>SMM as a routine dietary supplement.
screw that, include it in the acetaminophen tablets!
J.
randall
> On Sun, 29 Nov 2009 12:49:09 -0800 (PST), randall <ranhu...@aol.com>
J,
Exactly what big pharmA would say.
Why allow folks to unSCREW their pains and aches with NAC?
Yet are we NOT resPonsible for our OWN HEALTH ultimately?
But if big PIG GOV said to put another warning on the label,
Such as TAKE NAC to fortify your phase II detox enzymes GPX and SOD
how many would do THAT?
Maybe a few percent at most?
Let me google this...
No, wait, I'll try pubmed first.
pubmed: keywords:: acetaminophen glutathione [1235 hits]
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=acetaminophen+glutathione&log$=activity
And adding two kickers: gpx + SOD to the above search for 12 hits
including pmid: 19934368
acetaminophen glutathione sod gpx [12 hits on pubmed]
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=acetaminophen+glutathione+sod+gpx&log$=activity
The second looks good:
www.ncbi.nlm.nih.gov/pubmed/19799668
Protective effects from carnosine and histidine on acetaminophen-
induced liver injury.
[...]
However, the pre-intake of carnosine or histidine significantly
alleviated acetaminophen-induced oxidative stress by increasing GSH
content, decreasing MDA, ROS, and GSSG formations, and retaining
activity of GPX, catalase, and SOD in liver (P < 0.05). The pre-intake
of these compounds also significantly retarded subsequent
acetaminophen-induced increase of cytochrome P450 2E1 activity (P <
0.05). Acetaminophen treatment increased the hepatic levels of
interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, and
monocyte chemoattractant protein (MCP)-1 (P < 0.05). The pre-intake of
carnosine or histidine significantly diminished acetaminophen-induced
elevation of these cytokines (P < 0.05). The impact of these compounds
on mRNA expression of GPX, TNF-alpha, and MCP-1 indicated that these
compounds could act at a transcription level. These results support
that carnosine and histidine are potent hepatoprotective agents.
PMID: 19799668
OK, carnosine and histidine were big in our group a while back iirc.
Moving back to the other search.
The third most recent in the 1235 search looks interesting.
www.ncbi.nlm.nih.gov/pubmed/19931551
2009 Nov 18. [Epub ahead of print]
BGP-15 inhibits caspase-independent programmed cell death in
acetaminophen-induced liver injury.
Nagy G, Szarka A, Lotz G, Dóczi J, Wunderlich L, Kiss A, Jemnitz K,
Veres Z, Bánhegyi G, Schaff Z, Sümegi B, Mandl J.
Department of Medical Chemistry, Molecular Biology and
Pathobiochemistry, Semmelweis University, HAS Pathobiochemistry
Research Group, H-1444 Budapest POB 260, Hungary.
It has been recently shown that acute acetaminophen toxicity results
in endoplasmic reticulum redox stress and an increase in cells with
apoptotic phenotype in liver. Since activation of effector caspases
was absent, the relevance of caspase-independent mechanisms in
acetaminophen-induced programmed cell death was investigated. BGP-15,
a drug with known protective actions in conditions involving redox
imbalance, has been co-administered with a single sublethal dose of
acetaminophen. Proapoptotic events and outcome of the injury were
investigated. ER redox alterations and early ER-stress-related
signaling events induced by acetaminophen, such as ER glutathione
depletion, phosphorylation of eIF2alpha and JNK and induction of the
transcription factor GADD153, were not counteracted by co-treatment
with BGP-15. However, BGP-15 prevented AIF mitochondria-to-nucleus
translocation and mitochondrial depolarization. BGP-15 co-treatment
attenuated the rate of acetaminophen-induced cell death as assessed by
apoptotic index and enzyme serum release. These results reaffirm that
acute acetaminophen toxicity involves oxidative stress-induced caspase-
independent cell death. In addition, pharmacological inhibition of AIF
translocation may effectively protect against or at least delay
acetaminophen-induced programmed cell death.
PMID: 19931551
ER (endoplasmic reticulum ) is a hot zone besides the Gi tract (ileum
with sFB's) for psoriasis.
WELL, my hot zones anyway. <w>
Is SFB the macro crap and ER where the genetic micro mischief occurs?
Try 28 hits -- keywords:: ER + psoriasis
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=endoplasmic+reticulum+psoria*&log$=activity
--------
And a stab at TLR's with psoria* in the next few abstracts:
TLR accessory molecules.
Akashi-Takamura S, Miyake K.
Division of Infectious Genetics, Department of Microbiology and
Immunology, The Institute of Medical Science, The University of Tokyo,
4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
Accessory molecules are required for microbial recognition by Toll-
like receptor (TLR), subsequent signaling, and regulation of ensuing
immune responses. Accessory molecules regulate TLRs on the cell
surface (MD-2 and RP105), or in the endoplasmic reticulum (ER)
(Unc93B, PRAT4A, and gp96). Other types of accessory molecules
modulate TLR responses by acting directly on TLR ligands (CD14, CD36,
HMGB1, and the antimicrobial peptide LL37). These molecules cooperate
with TLR, inducing appropriate defense mechanisms. It is important to
understand how TLR signaling is controlled by these accessory
molecules. These accessory molecules could be promising targets for
therapeutic intervention in infectious disease and immune disorders.
PMID: 18625310
www.ncbi.nlm.nih.gov/pubmed/19703986
2009 Aug 31;206(9):1983-94. Epub 2009 Aug 24.
Self-RNA-antimicrobial peptide complexes activate human dendritic
cells through TLR7 and TLR8.
Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V,
Homey B, Barrat FJ, Zal T, Gilliet M.
Department of Immunology, The University of Texas M.D. Anderson Cancer
Center, TX 77030, USA.
Dendritic cell (DC) responses to extracellular self-DNA and self-RNA
are prevented by the endosomal seclusion of nucleic acid-recognizing
Toll-like receptors (TLRs). In psoriasis, however, plasmacytoid DCs
(pDCs) sense self-DNA that is transported to endosomal TLR9 upon
forming a complex with the antimicrobial peptide LL37. Whether LL37
also interacts with extracellular self-RNA and how this may contribute
to DC activation in psoriasis is not known. Here, we report that LL37
can bind self-RNA released by dying cells, protect it from
extracellular degradation, and transport it into endosomal
compartments of DCs. In pDC, self-RNA-LL37 complexes activate TLR7
and, like self-DNA-LL37 complexes, trigger the secretion of IFN-alpha
without inducing maturation or the production of IL-6 and TNF-alpha.
In contrast to self-DNA-LL37 complexes, self-RNA-LL37 complexes also
trigger the activation of classical myeloid DCs (mDCs). This occurs
through TLR8 and leads to the production of TNF-alpha and IL-6, and
the differentiation of mDCs into mature DCs. We also found that self-
RNA-LL37 complexes are present in psoriatic skin lesions and are
associated with mature mDCs in vivo. Our results demonstrate that the
cationic antimicrobial peptide LL37 converts self-RNA into a trigger
of TLR7 and TLR8 in human DCs, and provide new insights into the
mechanism that drives the auto-inflammatory responses in psoriasis.
PMID: 19703986 [PubMed - indexed for MEDLINE]
Six hits for psoria* + LL37
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=ll37+psoria*&log$=activity
25 hits if you put (-) between LL&37 (LL-37)
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=ll-37+psoria*&log$=activity
Five hits for keywords :: ll-37 OR ll37 AND endosomal
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=ll-37+OR+ll37+AND+endosomal&log$=activity
74 hits in our P NG for keyword: endosomal
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=endosomal
Brings back the invariant chain... hadn't thought of it in a while
www.ncbi.nlm.nih.gov/pubmed/16094690?dopt=Abstract
2005 Sep;35(9):2552-62.
In vivo control of endosomal architecture by class II-associated
invariant chain and cathepsin S.
Boes M, van der Wel N, Peperzak V, Kim YM, Peters PJ, Ploegh H.
Department of Pathology, Harvard Medical School, Boston, MA 02115,
USA. mb...@rics.bwh.harvard.edu
The invariant chain (Ii) is a chaperone that regulates assembly and
transport of class II MHC molecules. In the absence of the lysosomal
protease cathepsin S (CatS), degradation of Ii is impaired and an Ii
remnant that extends from the N terminus to about residue 110
accumulates in class II MHC-positive endosomal compartments, which are
enlarged in size and lack multivesicular morphology. In primary B
cells examined in vitro and in lymph nodes examined by immuno-electron
microscopy, CatS controls architecture of class II-positive endosomal
compartments. In a compound mutant mouse that lacks both CatS and Ii,
the normal size of endosomes in class II-positive cells is restored,
although internal endosomal membranes are absent. Proper degradation
of Ii is thus essential for normal endosomal morphology in antigen-
presenting cells in vivo.
PMID: 16094690
the second hit in those 74 hits for endosomal:
Wed, May 20 2009 12:16 pm
Subject: TLR's & CD Blockers -- Vitamin D -- Immune Links - Flu Links
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/d1d7eefe656d8a7e
[...]
http://www.ncbi.nlm.nih.gov/pubmed/18613842
Development of TLR inhibitors for the treatment of autoimmune
diseases.
Barrat FJ, Coffman RL.
Dynavax Technologies Corporation, Berkeley, CA 94710, USA.
fbar...@dynavax.com
SUMMARY: The innate immune system is a critical element of protection
from invading pathogens. The specific receptors that recognize
various
components of the pathogens trigger signals that result in the
production of proinflammatory cytokines as well as the activation of
antigen-presenting cells, which activate the adaptive immune system.
The discovery of the Toll-like receptors (TLRs) as important
components of pathogen recognition has brought new understanding of
the key signaling molecules involves in innate immune activation.
Interestingly, it appears that most TLRs can recognize self-ligands
as
well and that mechanisms are required to discriminate between self
and
non-self ligands. One of these mechanisms is the expression of all
the
nucleic acid-specific TLR in endosomal compartments and not on the
cell surface. Inappropriate activation of TLRs by self-components can
result in sterile inflammation or autoimmunity. For example, TLR7 and
TLR9 activation by endogenous RNA and DNA, transported to the
endosomes in the form of immune complexes or non-covalently
associated
with cationic peptides, could be an important mechanism involved in
promoting diseases such as systemic lupus erythematosus and
psoriasis.
In this review, we discuss the rationale for self-recognition by TLR7
and TLR9 as an important part of the development of lupus and other
autoimmune diseases. We describe novel inhibitors of these receptors
and provide evidence to support their use as novel therapeutic agents
for autoimmunity.
PMID: 18613842
-----------
So what?
Well, they want to block: TLR7 and 9
http://en.wikipedia.org/wiki/TLR_7
Toll-like receptor 7, also known as TLR7, is an immune gene possessed
by humans and other mammals and additionally in avian species.
The protein encoded by this gene is a member of the Toll-like
receptor
(TLR) family which plays a fundamental role in pathogen recognition
and activation of innate immunity. TLRs are highly conserved from
Drosophila to humans and share structural and functional
similarities.
They recognize pathogen-associated molecular patterns (PAMPs) that
are
expressed on infectious agents, and mediate the production of
cytokines necessary for the development of effective immunity. The
various TLRs exhibit different patterns of expression. This gene is
predominantly expressed in lung, placenta, and spleen, and lies in
close proximity to another family member, TLR8, on human chromosome
X.
[1] Imiquimod acts upon TLR 7.[2]
TLR7 recognises single stranded RNA in endosomes, which is a common
feature of viral genomes which are internalised by macrophages.
<sniP>
And nine does look better for cpg's.
Do a search of this group for unmethylated anything and see for your
self. LOL
http://en.wikipedia.org/wiki/TLR_9
TLR 9 is a toll-like receptor.
It recognizes unmethylated CpG sites on DNA molecules. CpG sites are
relatively rare (~1%) on vertebrate genomes in comparison to
bacterial
genomes or viral DNA. TLR9 is expressed by numerous cells of the
immune system such as dendritic cells, B lymphocytes and natural
killer (NK) cells. TLR9 is expressed intracellularly, within the
endosomal compartments and functions to alert the immune system of
viral and bacterial infections by binding to DNA rich in CpG motifs.
TLR9 signals leads to activation of the cells initiating pro-
inflammatory reactions that result in the production of cytokines
such
as type-I inteferon and IL-12. There are new immunomodulatory
treatments undergoing testing which involve the administration of
artificial DNA oligonucleotides containing the CpG motif. CpG DNA has
applications in treating allergies such as asthma, immunostimulation
against cancer, immunostimulation against pathogens, and as adjuvants
in vaccines.
<sniP>
<snip of the sniP>
===============================================
14 hits for invariant chain in the P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=invariant+chain
http://en.wikipedia.org/wiki/Invariant_chain
The invariant chain is a special polypeptide involved in the formation
and deliverance of MHC class II protein.
The nascent MHC class II protein in the rough ER has its peptide-
binding cleft blocked by the invariant chain (Ii; a trimer) to prevent
it from binding cellular peptides or peptides from the endogenous
pathway. The invariant chain also facilitates MHC class II's export
from the ER in a vesicle. This fuses with a late endosome containing
the endocytosed, degraded proteins. It is then cleaved by cathepsin S,
leaving only a small fragment called CLIP which blocks peptide binding
until HLA-DM binds to MHC II, releasing CLIP and allowing other
peptides to bind. The stable MHC class-II is then presented on the
cell surface.
The cell surface form of the invariant chain is known as CD74.
<sniP>
-------------
And i see only two abstracts with cd74 and psoria* on pubmed and both
are with cancerous conditions.
Where was i?
LOL
I did start another thread earlier. I'll finish it instead. LOL
I got sidelined and can't recall if I made any sense on anti sense
matters.
LOL funny?
Well maybe if the joke is on top of us as psoriasis you goon.
Who you calling a goon?
You.
But your me.
i know and it's in your gene's. LOL
http://en.wikipedia.org/wiki/Antisense_therapy
randall... oh WELL, after i read this tomorrow it might make SENSE.
<G>