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randall

unread,

Aug 7, 2005, 3:44:20 PM8/7/05

Hi,

There were so many broken links in the last P news post (#91 or 92).
That
it became the last post in that thread. :(

Oh well, all good things for P will make them selves known. Broken
links
or not. Amen! let the miracles of science begin.

One of my favorite aids, melatonin, to a sound sleep has deePer
ramifications
then I knew,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11506187

Melatonin enhances Th2 cell mediated immune responses: lack of
sensitivity to reversal by naltrexone or benzodiazepine receptor
antagonists.

Raghavendra V, Singh V, Kulkarni SK, Agrewala JN.

Immunology Laboratory, Institute of Microbial Technology, Chandigarh,
India.

Chronic administration of melatonin for 5 days to antigen-primed mice
increased the production of pro-inflammatory cytokine IL-10 but
decreased the secretion of anti-inflammatory cytokine TNF-alpha. These
results further confirm that melatonin activates Th2-like immune
response. Whether melatonin-mediated Th2 response is dependent on
opioid or central and peripheral benzodiazepine receptors was also
examined. Hence, melatonin was administered to antigen-sensitised mice
with either naltrexone (a mu opioid receptor antagonist) or flumazenil
(a central benzodiazepine receptor antagonist) or PK11195 (a peripheral
benzoidiazepine receptor antagonist). No significant difference in
melatonin-induced Th2 cell response was observed by naltrexone,
flumazenil or PK11195 treatment. These findings suggest that the Th2
cell response induced by melatonin in antigen sensitised mice neither
dependent on endogenous opioid system nor is modulated through the
central or peripheral benzodiazepine receptors.

*****

Melatonin increased IL-10! Exactly what we need more of. Feel free to
experiment with it and report back. I take 1 mg half hour before bed.

Now this is a miracle if we can alter our Th1 skew back towards the
norm
some.

******

I've started another P test with IP6 yesterday. IP6 the compound from
cereals, legumes, nuts, oil seeds and soybeans has unique properties
that many have found useful in the treatment of their cancers! Most
use it as an adjunct now, but that may change.

These current abstracts make it hard to figure out why it works so
well,
(for me/P being Th1 as some of this is rather counterintuitive)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10834203
The effects of inositol hexaphosphate on the inflammatory response in
transformed RAW 264.7 macrophages.

Johnson M, Tucci M, Benghuzzi H, Cason Z, Hughes J.

University of Mississippi Medical Center, Jackson 39216, USA.

Inositol hexaphosphate (IP6) has received much attention for its role
in interfering with tumor progression and slowing the metastasis of
neoplastic cells. However, there is little information regarding the
antioxidant properties of IP6 or its ability to enhance the natural
disease resistance of the body. The specific objectives of this
experiment were to investigate the effects that IP6 might have on the
proliferation and viability of RAW 264.7 transformed macrophages and to
morphologically and biochemically investigate the role of IP6 as a free
radical scavenger. Transformed RAW macrophages were obtained from the
American Type Culture Collection (Rockville, MD) and maintained in
sterile media (RPMI) supplemented with 10% fetal bovine serum and 1%
antibiotics and antimycotics. The cells were plated on to 24 well
plates at a density of 1 x 10(5) cells/well. The cells were divided
into five groups of four wells per group per phase (24, 48, and 72
hours). Cells in Group I were treated with media alone and served as
controls. Cells in Group II were treated with lipopolysaccharide (LPS)
only. Cells in groups III, IV, and V were treated with 1000 microliters
of IP6 + LPS, 500 microliters of IP6 + LPS, and 100 microliters of IP6
+ LPS, respectively. Cell numbers, as well as, morphology, MDA, and
protein were determined at the end of 24, 48, and 72 hours. Data
obtained from this investigation revealed that the rate of cell
proliferation was totally dependent on the dose of IP6. At 24 and 48
hours and upon the exposure of high dose of IP6 the mitotic ability of
the cells was higher (p < 0.05) than the rate at the 72 hour phase.
Morphological evaluation of cells at all three phases revealed that
there were significant changes in the architecture of cells upon the
exposure of IP6 compared to the control group. The results of this
study suggest that IP6 may have had an excitatory effect on the
inflammatory cell secretions and this phenomenon was found to be dose
dependent.

PMID: 10834203

Yet with P does IP6 make the cells pop even faster? Pop goes the P
weasels?
That would be the skin cells that pop? Wouldn't they just plaque up
faster?

And this next one makes even less sense to the randall's whey proflora
theory.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15460064
Biodiversity of human faecal bacteria isolated from phytic acid
enriched chemostat fermenters.

Steer TE, Gee JN, Johnson IT, Gibson GR.

Food Microbial Sciences Unit, School of Food Biosciences, The
University of Reading, Whiteknights, PO Box 226, Reading, RG6 6AP, UK.

BACKGROUND: Myo-inositol hexaphosphate (IP6) or phytic acid is found
mostly in cereals and legumes and is thought to possess
anti-carcinogenic properties. AIM: To isolate and identify faecal
bacteria capable of phytic acid metabolism and to assess the
effectiveness of prebiotics (dietary oligosaccharides, metabolised by
selective colonic bacteria) in preserving the integrity of phytic acid.
METHODS: Faecal samples from three volunteers were used in continuous
culture experiments under varying conditions of pH, substrate
concentration and dilution rates, seventy three different isolates
cultured at steady state were then screened for phytic acid metabolism
and identified through partial sequencing of their 16S rRNA genes (16S
ribosomal ribonucleic acid). Utilisation of phytic acid was also
assessed in a continuous culture system enriched with prebiotic
fructooligosaccharides (FOS). RESULTS: Bacteroides spp., Clostridium
spp. and facultatively anaerobic bacteria generally appeared to
maintain viable counts in the presence of phytic acid. Bifidobacterium
spp. and Lactobacillus spp. appeared less able to maintain viable
counts in the presence of phytic acid. These results were confirmed by
an increase in viable counts of Bacteroides spp., Clostridium spp. and
a decrease in viable counts of Bifidobacterium spp. and Lactobacillus
spp. once phytic acid was introduced to a FOS enriched continuous
culture. CONCLUSIONS: The phytate metabolising biodiversity from the
human large intestine does not appear to encompass major bacterial
genera associated with beneficial or benign health effects (e.g.
Lactobacillus spp. and Bifidobacterium spp).

PMID: 15460064

Yet, iP6 has other good things that go on for the cancer patient.

But how does one fit the Th1/Th2 theory to iP6?

Does it help the P Th1 side as well as the cancer Th2 side of immunity?

IP6 anti-angiogenic properties help P,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15297368

IP6 inhibits constitutive activation of NF- kappa B in hp cells
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14666688

IP6 decreases cell adhesion by suppressing the integrin receptors and
their subsequent signaling pathway,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14666664

Wheat has screwed the psoriatic in the past. Now it can be MADE to work
for us.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15801778
Treatment of germinated wheat to increase levels of GABA and IP6
catalyzed by endogenous enzymes.

Nagaoka H.

Sanyo Foods Co., Ltd., Research and Development, 555-4 Asakura,
Maebashi, Gunma 371-0811, Japan. naga...@sea.plala.or.jp

We found that the levels of bioactive products from wheat can be
increased dramatically by manipulating germination conditions and
taking advantage of the activity of endogenous enzymes. The yield of
phytic acid (IP(6)) from wheat germinated in the presence of high,
controlled levels of dissolved oxygen (188 +/- 28 mg/100 g wheat) was
almost three times greater than that from wheat germinated with no
supplemental oxygen (74 +/- 10 mg/100 g wheat). The yield of
gamma-aminobutyric acid (GABA) from wheat germinated in the presence of
uncontrolled levels of dissolved oxygen was 18 +/- 3 times greater than
that from nonsupplemented wheat (1 mg/100 g wheat). The concentration
of GABA was much greater in wheat germ than in whole wheat, and the
yield of GABA from wheat germ processed with supplemental water (163
+/- 7 mg/100 g wheat germ) was notably greater than that from wheat
germ processed with no supplemental water (100 +/- 2 mg/100 g wheat
germ). In contrast, IP(6) was more concentrated in wheat bran, and the
yield of IP(6) from wheat bran processed with supplemental water (3100
+/- 12 mg/100 g wheat bran) was notably higher than that from wheat
bran processed with no supplemental water (2420 +/- 13 mg/100 g wheat
bran). We conclude that the large amount of GABA extracted from wheat
germ is likely due to high glutamate decarboxylase activity and low
aminotransferase activity and that the large amount of IP(6) extracted
from wheat bran is likely due to high levels of tyrosinase activity.
Our findings indicate that bioactive molecules such as GABA and IP(6)
can be successfully mass-produced by taking advantage of endogenous
enzymatic activities.

PMID: 15801778

Wow, making iP6 with O2 seems like a cool way to make a bunch of it.
And you have all that extra GABA to fool around with. Now you can
really relax and sleep well.

^^^^^^^^^^^^^^

Back to the abstracts.

This one brings up big questions to arginine flares for the psoriatic,
see:
http://groups-beta.google.com/groups?q=arginine+psoriasis&qt_s=Search
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16082501

Almost all about citrulline in mammals.

Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Benazeth S,
Cynober L.

Laboratoire de Biomathematiques, E.A. 2498, Faculte de Pharmacie,
Universite Rene Descartes, Paris, France.

Citrulline (Cit, C(6)H(13)N(3)O(3)), which is a ubiquitous amino acid
in mammals, is strongly related to arginine. Citrulline metabolism in
mammals is divided into two fields: free citrulline and citrullinated
proteins. Free citrulline metabolism involves three key enzymes: NO
synthase (NOS) and ornithine carbamoyltransferase (OCT) which produce
citrulline, and argininosuccinate synthetase (ASS) that converts it
into argininosuccinate. The tissue distribution of these enzymes
distinguishes three "orthogonal" metabolic pathways for citrulline.
Firstly, in the liver, citrulline is locally synthesized by OCT and
metabolized by ASS for urea production. Secondly, in most of the
tissues producing NO, citrulline is recycled into arginine via ASS to
increase arginine availability for NO production. Thirdly, citrulline
is synthesized in the gut from glutamine (with OCT), released into the
blood and converted back into arginine in the kidneys (by ASS); in this
pathway, circulating citrulline is in fact a masked form of arginine to
avoid liver captation. Each of these pathways has related pathologies
and, even more interestingly, citrulline could potentially be used to
monitor or treat some of these pathologies. Citrulline has long been
administered in the treatment of inherited urea cycle disorders, and
recent studies suggest that citrulline may be used to control the
production of NO. Recently, citrulline was demonstrated as a
potentially useful marker of short bowel function in a wide range of
pathologies. One of the most promising research directions deals with
the administration of citrulline as a more efficient alternative to
arginine, especially against underlying splanchnic sequestration of
amino acids. Protein citrullination results from post-translational
modification of arginine; that occurs mainly in keratinization-related
proteins and myelins, and insufficiencies in this citrullination occur
in some auto-immune diseases such as rheumatoid arthritis, psoriasis or
multiple sclerosis.

PMID: 16082501

This next one works to help explain IP6 for P and cancer.
With the chelating effects of ip6, one may be blocking
calcium pathways as well as iron,
http://groups-beta.google.com/groups?q=calcium+ion+psoriasis&qt_s=Search

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16082188

Psoriasin (S100A7) and Calgranulin-B (S100A9) Induction is Dependent on
Reactive Oxygen Species and is Downregulated by Bcl-2 and Antioxidants.

Carlsson H, Yhr M, Petersson S, Collins N, Polyak K, Enerback C.

Department of Clinical Genetics, Sahlgrenska University Hospital,
Goteborg, Sweden.

S-100 proteins are calcium-binding proteins with important growth
regulatory functions. Of these proteins, psoriasin and calgranulin-B
have been shown to be highly upregulated in ductal carcinoma in situ
(DCIS) of the breast and in psoriasis. The purpose of this study was to
further elucidate the functional relevance of the overexpression of
these two S-100 proteins in psoriasis and DCIS. We report the induction
of both proteins by reactive oxygen species, phorbol ester TPA, and the
induction of psoriasin in response to the PI3K inhibitor wortmannin. We
also demonstrate that Bcl-2 overexpression represses the induction of
psoriasin and calgranulin-B under these different conditions. The same
effect was obtained with the antioxidant NAC, which indicates that the
suppression of psoriasin and calgranulin-B induction is mediated by the
antioxidant function of Bcl-2. Furthermore, we demonstrate that
overexpression of a dominant negative IKKbeta also inhibits the
induction of psoriasin suggesting that the NFkappaB pathway is involved
in the induction of this protein. Also, we found NFkappaB responsive
DNA elements in the upstream promoter region of psoriasin. MCF10A cells
with a stable retroviral overexpression of psoriasin were significantly
more resistant to H(2)O(2)-induced cell death than control cells
further supporting the hypothesis that these S-100 proteins may play a
role in oxidative stress response.

PMID: 16082188

Note: I take about a half gram a day of NAC on average.

This next one fits in well with the last in the thread of P news.

How does LPS affect polymorphisms of TNF,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12761565

Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFalpha
production induced by Gram-positive and Gram-negative bacteria.

Temple SE, Cheong KY, Almeida CM, Price P, Waterer GW.

Department of Medicine, University of Western Australia, Royal Perth
Hospital, Perth, Australia. sete...@cyllene.uwa.edu.au

Improved understanding of how host genetic variation affects resistance
to microbial pathogens could lead to better treatment and/or prevention
of infectious diseases. The lymphotoxin alpha (LTA)+250 and CD14-159
polymorphisms are associated with differences in susceptibility or
outcome to several infections. We stimulated peripheral blood
mononuclear cells (PBMC) from 22 healthy individuals with purified
lipopolysaccharide (LPS), heat-killed Escherichia coli or Streptococcus
pneumoniae. TNF alpha intracellular protein levels were measured by
flow cytometry and mRNA was quantitated by RT-PCR. TNF alpha mRNA
levels were higher in LTA+250GG subjects after 4 h incubation with LPS
compared with LTA+250AA (T test, P=0.001). In contrast, after 8 h
incubation with S. pneumoniae, there was slightly more TNF alpha mRNA
in cells from LTA+250AA subjects. After 4 h incubation with LPS or E.
coli, CD14-159TT subjects had higher TNF alpha mRNA levels than
CD14-159CC (P=0.05, 0.033, respectively). Neither polymorphism affected
the proportion of cells expressing intracellular TNF alpha protein.
This suggests that the polymorphisms affected transcription and that
other regulatory mechanisms affect production of TNF alpha protein. The
effect of these two polymorphisms on TNF alpha mRNA production is
stimulus dependent, with opposite effects observed for Gram-positive
and Gram-negative stimuli.

PMID: 12761565

randall... real science not miracle water to baPtease your self with.

raydon14yp

unread,

Aug 9, 2005, 11:48:20 AM8/9/05

Randall-You must be a speed reader to post all the informative info.
Thanks for it!!!

randall

unread,

Aug 9, 2005, 12:17:36 PM8/9/05

Hi,

This one was so much fun, i figured you'd want to read it too.

http://www.foxnews.com/story/0,2933,165103,00.html

Researchers may have figured out how a drug called methoxsalen may help
smokers quit smoking. Methoxsalen blocks nicotine breakdown, write
Jason Yano, PhD, and colleagues in Nature Structural & Molecular
Biology. With nicotine intact, smokers may not crave cigarettes as much

Methoxsalen also appears to block cancer-causing chemicals in tobacco
from breaking down into even more harmful components, write the
researchers.

The findings could lead to new quit-smoking medicines, writes Yano. He
works in the molecular and experimental medicine department of the
Scripps Research Institute in La Jolla, Calif.

Read WebMD's "Smoking Cigarettes Affects Brain Like Heroin"

About Methoxsalen

Methoxsalen's brand names include Oxsoralen, Oxsoralen-Ultra, Uvadex,
8-MOP, and, in Canada, Ultra MOP.

Methoxsalen is in a group of drugs called psoralens. It is used along
with ultraviolet light to treat the skin conditions psoriasis and
vitiligo, as well as a type of lymphoma called mycosis fungoides.

Read WebMD's "Quitting Smoking? Don?t Gain Weight"

Side Effects

Methoxsalen is a prescription drug that requires close medical
supervision. It was not originally designed to help people quit
smoking.

Methoxsalen's side effects include sensitivity to light, skin cancer,
premature skin aging, and cataracts. Being exposed to sun while taking
methoxsalen can lead to serious burns.

The drug is also not recommended for pregnant patients. It's not known
if the drug can be passed through breast milk, so women who breastfeed
should discuss the drug's risks with their doctor.

Methoxsalen may react with certain foods (such as carrots, celery,
figs, limes, mustard, and parsley). Those foods should be avoided while
taking methoxsalen.

Read WebMD's "CDC: Smoking Rates Continue to Drop"

Drug's Effects on Nicotine

How does methoxsalen affect nicotine and tobacco? The drug targets a
protein called CYP2A6, which breaks down nicotine and tobacco's
cancer-causing chemicals, write the researchers.

Yano and colleagues aren't recommending methoxsalen to smokers. They
didn't test the drug on smokers who wanted to kick the cigarette habit.
Instead, Yano's team wanted to figure out how methoxsalen affected
CYP2A6.

Methoxsalen's structure "should aid the design of inhibitors to reduce
smoking and tobacco-related cancers," write the researchers.

(I can hardly wait to do the heroin search in the group now!)

^^^^^^^^^^^^^^^

In the Pubmed abstracts today. Goeckerman therapy changes to your blood
etc.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16083312
Cytogenetic and immunological changes after dermal exposure to
polycyclic aromatic hydrocarbons and UV radiation.

Borska L, Fiala Z, Krejsek J, Hamakova K, Andrys C, Smejkalova J,
Vokurkova D, Kremlacek J.

Institute of Pathological Physiology, Charles University in Prague,
Faculty of Medicine in Hradec Kralove, Simkova 870, 500 38, Hradec
Kralove, Czech Republic. bo...@lfhk.cuni.cz.

Goeckerman's therapy (GT), which combines exposure to coal tar
(polycyclic aromatic hydrocarbons - PAHs) and UV radiation (UV) is
often used as the first option for treatment of psoriasis. However,
PAHs and UV represent mutagenic, carcinogenic and immunotoxic agents.
Therefore GT can represent a health risk for the patients. The group
under observation consisted of thirty patients undergoing GT. Before
and after the therapy blood samples were collected, from which
chromosomal aberrations and selected immunological markers were
determined. The relationships between chromosomal aberrations and
immunological markers and the extent (duration) of exposure to GT were
evaluated. The Psoriasis Area and Severity Index (PASI) score confirmed
high efficiency of GT. However, significantly elevated levels of
chromosomal aberrations of peripheral lymphocytes were also found after
the therapy (p<0.001). The levels of chromosomal abnormalities
correlated to the extent and the total duration of exposure to PAHs
(r=0.682, p<0.01 and r=0.605, p<0.05). After the therapy significantly
decreased levels of IgE, IgM isotypes of immunoglobulin,
alpha(2)-macroglobulin and ____transferrin___ together with
beta(2)-microglobulin were found. From the immunological markers listed
above only the decreased level of alpha(2)-macroglobulin correlated to
the extent of exposure to PAHs (r = -0.568, p<0.05). No correlation
between chromosomal aberrations, significantly changed immunological
markers and duration of UV exposure were found. Our study revealed that
GT has a significant impact on both genetic and immunological
parameters of psoriatic patients. The results indicate that GT could
increase genotoxic risk and modulates immunity of treated patients.

PMID: 16083312

Lets look at transferrin,
http://sickle.bwh.harvard.edu/iron_transport.html

Whats so good about less of it?
http://sickle.bwh.harvard.edu/iron_absorption.html
Slide show for how much fe is just right,
http://www.nature.com/nrg/journal/v1/n3/slideshow/nrg1200_208a_F2.html

What does it do to a P gut? Make more P?

It may as well, as we know that IP6 lowers P without
radiation or coal tar aPPlications.

Thats right IP6 from cereal and NOT GT from sunshine and tar
and return your iron levels to homeostasis. Don't go to whacko now.
Fall outa balance and you could become JackO Jackson. lol

I'm on my fourth day taking IP6 btw and my P is about 20% better
without
changing my very bad diet (part of the trial) in the least.

For around $10-$20 you can purchase 120 caps of 500 mg's and
do your own trials.

Jarrow and enzymatic therapy both have IP6 for those cancer
patients wishing to lower iron levels. Unfeeding the funk may
allow the body to attain higher levels of health. So toss off the
anchor on your own innate health. Sorta like being a vegetarian
as far as the iron consumption goes anyway.

What else is uP on pubmed,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16084129
Malassezia Baillon, emerging clinical yeasts.

Batra R, Boekhout T, Gueho E, Cabanes FJ, Dawson TL Jr, Gupta AK.

Mediprobe Research, London, Ont., Canada.

The human and animal pathogenic yeast genus Malassezia has received
considerable attention in recent years from dermatologists, other
clinicians, veterinarians and mycologists. Some points highlighted in
this review include recent advances in the technological developments
related to detection, identification, and classification of Malassezia
species. The clinical association of Malassezia species with a number
of mammalian dermatological diseases including dandruff, seborrhoeic
dermatitis, pityriasis versicolor, psoriasis, folliculitis and otitis
is also discussed.

PMID: 16084129

Doesn't more iron make it easier for funGUS to get a griP?

http://pathmicro.med.sc.edu/mycology/opportunistic.htm

"Opportunistic mycoses are infections due to fungi with low inherent
virulence which means that these pathogens constitute an almost
limitless number of fungi. "

Yet, aren't they more oPPortunistic if you feed them?

Go ahead and turn your self into a human Petri dish and do your own
trials.

Go buy some Geritol if you wish to try to induce a flare.

Be careful of these tests as strange things may occur,
http://www.handguncontrolinc.org/suckerman.htm

And good luck getting the iron out,

randall... drugs, guns, GT, germs. who says P isn't fun?

randall

unread,

Aug 9, 2005, 12:25:15 PM8/9/05

raydon14yp wrote:
> Randall-You must be a speed reader to post all the informative info.
> Thanks for it!!!

Or logically, on sPeed!

Oddly enough its all au natural from a non nude perspective.

I mean i have to do it fast as I have a life to CRAM into the other
22-23.5 hours in the day. I can get by on less sleeP, but not
now on the iron free diet via IP6.

randall.. just the P skinny ma'am!

randall

unread,

Aug 10, 2005, 1:09:41 PM8/10/05

randall wrote:

> Lets look at transferrin,
> http://sickle.bwh.harvard.edu/iron_transport.html
>
> Whats so good about less of it?

But we want less because its tying uP iron? Right?

> http://sickle.bwh.harvard.edu/iron_absorption.html
> Slide show for how much fe is just right,
> http://www.nature.com/nrg/journal/v1/n3/slideshow/nrg1200_208a_F2.html

<sniP>

> I'm on my fourth day taking IP6 btw and my P is about 20% better
> without
> changing my very bad diet (part of the trial) in the least.

It's given license to even cheat/eat more. But this stuff takes the
starch outa me by the end of the day and i'm trying to
get the LPS to leak and eat bad! Quite a task if you don't feel
up to tying one on every night.

Still,

Day five looking about 50% better on only one half gram (500mg's).

Thinking about going to one gram tomorrow.

> For around $10-$20 you can purchase 120 caps of 500 mg's and
> do your own trials.
>
> Jarrow and enzymatic therapy both have IP6 for those cancer
> patients wishing to lower iron levels. Unfeeding the funk may
> allow the body to attain higher levels of health. So toss off the
> anchor on your own innate health. Sorta like being a vegetarian
> as far as the iron consumption goes anyway.

Fizziwig2

unread,

Aug 10, 2005, 1:51:13 PM8/10/05

"randall" <ranh...@aol.com> wrote in message
news:1123693781.3...@g44g2000cwa.googlegroups.com...

If psoriasis has anything to do with iron would be a bit problematical for
me. I tend to get anaemic easily and it doesn't make any difference to my
psoriasis when the doctor prescribes extra iron.

Skeats

randall

unread,

Aug 10, 2005, 10:48:05 PM8/10/05

Skeats,

I do believe that its P DNA when the wheels hit the road at the end of
the day. And we have abnormal ROS due to many things. In my case if I
eat iron and arachidonic acid rich meat foods, its easier for the P to
manifest. And harder to stop the flares without stopping the offending
diet.

Obviously for you, all those things that go into this pathway may
not have much effect. Yet recall that i'm purposely eating a bad diet
(p wise) to test the effects of IP6 on my P. Which I have tested many
times before.

And I'm, what? Like five days into it and looking 50% clearer!

Maybe its something that can't be explained yet in these pathways and
it
helps you also. You could start with one quarter capsule every other
day.

After all its no different then eating a TON of cereal.

And if it does something for you. We have some thinking to do.

It's not like a very expensive trial and if it helps you haven't lost
anything but a few percent here and there. Oh wait? Your like nearly
clear now?

Never mind.

randall

unread,

Aug 14, 2005, 3:54:15 PM8/14/05

Hi,

P news. From around the world and this time from inside of me.
German and Japan news towards the end of this post and a UK
story of interest as well.

*****

Its been over a week now with my latest trial on IP6. Not so sure if
its
the iron poor blood or if i'm just feeling a little slow. :(

The starch is outa my shirt and pants and all with one gram a day of
IP6 no less. (IP6 chelates iron and other metals in your system)

Could it be my bodies cells are doing some house cleaning? If I was
to feel and act positive this would be the tack i'd like to take. The
glass
is half full and my p plaques are now half clear!
But, it seems like i've plateaued a bit with the P clearings, though
i'm
very haPPy with what i've seen this week. :)

What could be the reasons as it certainly isn't the P Cure, though it
works for me?

Whats it doing part II or III or whatever this one is.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15935567

Phytase activity as a novel metabolic feature in Bifidobacterium.

Haros M, Bielecka M, Sanz Y.

EU Centre of Excellence CENEXFOOD, Division of Food Science, Institute
of Animal Reproduction and Food Research of the Polish Academy of
Sciences, Tuwima 10, 10-747 Olsztyn, Poland.

Phytase activity has been detected for the first time in
Bifidobacterium spp. These bacteria were able to dephosphorylate phytic
acid (myo-inositol hexaphosphate, IP(6)) and generate several
myo-inositol phosphate intermediates (IP(3)-IP(5)). B. globosum and B.
pseudocatenulatum were optimally active at neutral-alkaline pH and B.
adolescentis, B. angulatum and B. longum at acid pH. B.
pseudocatenulatum showed the highest levels of phytase activity. This
species produced maximum activity in the exponential phase of growth
and when fructo-oligosaccharides were used as carbon source in the
culture medium. The potential role of phytase activity from
Bifidobacterium spp. in the reduction of the antinutritional properties
of IP(6) is discussed.

PMID: 15935567

Do you suPPose this last abstract means that you should have good flora
in your gut to make this IP6 stuff? Could that be why cancer prone
folks soak the
stuff up like a sponge? What hapens with it in the Gi tract?

Your gut cells love this cereal stuff (IP6) it gobbles it uP,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15909944

Wait you say? These are in caco-2 cells of the gut?

Ok,
http://groups-beta.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=caco-2&qt_g=1&searchnow=Search+this+group

Iron in the gut must not make the same BANG (P wise) when loads of
IP6-ish cereal is down there keeping those cells busy?

Eating an atkins diet thus requires heavy on the cereals to block those
turned
on inflammation recePtors or what?

Lets look at P as two conditions for arguments sake. One is trying to
stop
a perceived villain (the immune thing) and the other is crossing
signals
on a few pathways in the gut that stops autoimmunity? We are Th1 skewed
yet something else is at work here that must share a pathway or two
with
the Th2 cancer folks. Back to us.

Psoriasis is a chronic and recurrent inflammatory skin disease. The
inflammatory response represents a fundamental ability of the organism
to protect itself from infectious agents and from injury. OBJECTIVES:
To evaluate the inflammatory response in mild and in severe psoriasis,
to evaluate the endogenous systems counterbalancing the deleterious
effects of the inflammation products, and to establish values of
prognostic significance.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt«stract&list_uids 149504

All of the mentioned pathways show the Th1 skew and inflammation. does
mother nature attempt to clear it? Only with us that pathway switch is
turned on to long?

Now lets look closer at the cereal stuff, IP6.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt«stract&list_uids 834203

PMID: 10834203

So back to LPS and the psoriatic hair trigger immune thing? Looks like
it to me.

Who knows? Maybe IP6 slows ROS in general some how and attenuates P?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt«stract&list_uids 761133

And IP6 affects lipid levels and therefore PPARs,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt«stract&list_uids 625943

And if IP6 can't be coherently worked into a dietary regime for P.
Other more specific
treatments are in the piPeline.

http://www.redherring.com/Article.aspx?a 127&hed=Avontec+Raises+%2418+Million&sector=Regions&subsector=Europe

German biotech firm Avontec GmbH announced on Thursday that it has
raised ?14.5 million ($18 million) in a second round of financing that
combined an equity deal with a cross-licensing agreement.

The deal was co-led by Japanese biotech firm AnGes MG, through its
investment vehicle Bio-Sight Capital, and DVC Deutsche Venture Capital.

<sniP>

http://www.japancorp.net/Article.Asp?Art_ID 668
AnGes MG announced on August 10 that it has signed a cross licensing
agreement with German bio-venture company Avontec on the development of
decoy nucleic acid drugs.

Under the terms of the agreement, AnGes MG will be able to exclusively
use Avontec's proprietary technology STAT-1 decoy oligodeoxynucleotides
in Asia to develop applications for respiratory and respiratory and
skin diseases.

Meanwhile, Avontec will be granted the right to use NF-kappa B decoy
oligodeoxynucleotide (NFkB decoy oligo), a kind of nucleic acid
medicine developed by AnGes MG, in Europe with a view to applying it to
the treatment of psoriasis.

Avontec, which was launched by the Georg-August-University Goettingen
in Germany in 2001, specializes in research and development of nucleic
acid-based drugs.

****************

Lets look at aging research and try to tie their gains into our PAINS.
P wise off
course.

A Push and a Pull for PARP-1 in Aging
Does the DNA-repair mechanism fit into the longevity puzzle?

http://www.the-scientist.com/2005/08/01/22/1

Understanding the mechanisms that underlie aging remains a bedeviling
problem, but not because of a lack of answers. If anything, there seem
to be too many answers ? or at least enticing clues ? each leading in
different directions.

Thus, researchers are bound to get excited when a single molecule
appears to play roles in several perceived longevity pathways, raising
hopes that one could weave a coherent theory. Several strands of
evidence have linked PolyADP-ribose polymerase-1 (PARP-1) to potential
aging-associated processes such as DNA-repair, telomere maintenance,
and apoptosis. But many still question PARP's role in longevity. <sniP>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15778359&query_hl=5

IL-15 activates telomerase and minimizes telomere loss and may preserve
the replicative life span of memory CD8+ T cells in vitro.

Li Y, Zhi W, Wareski P, Weng NP.

Laboratory of Immunology, National Institute on Aging, National
Institutes of Health, Baltimore, MD 21224, USA.

The preservation of the replicative life span of memory CD8(+) T cells
is vital for long-term immune protection. Although IL-15 plays a key
role in the homeostasis of memory CD8(+) T cells, it is unknown whether
IL-15 regulates the replicative life span of memory CD8(+) T cells. In
this study, we report an analysis of telomerase expression and telomere
length in human memory phenotype CD8(+) T cells maintained by IL-15 in
vitro. We demonstrate that IL-15 is capable of activating telomerase in
memory CD8(+) T cells via Jak3 and PI3K signaling pathways.
Furthermore, IL-15 induces a sustained level of telomerase activity
over long periods of time, and in turn minimizes telomere loss in
memory CD8(+) T cells after substantial cell divisions. These findings
suggest that IL-15 activates stable telomerase expression and
compensates telomere loss in memory phenotype CD8(+) T cells, and that
telomerase may play an important role in memory CD8(+) T cell
homeostasis.

PMID: 15778359

While IL-15 is a Th1 cytokine, it doesn't look as bad as some of them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15560760

Could IL-15 being hanging out with the others and keeping us younger
looking?

If by blocking it, will we grow older faster?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15251134

nterleukin-15: a new cytokine target for the treatment of inflammatory
diseases.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14617758&query_hl=7

(...)
These results obtained with this IL-15-specific mAb support an
important role for IL-15 in the pathogenesis of psoriasis.

PMID: 14617758

^^^^^^^^^^

Are you on the NASH diet?
http://www.signonsandiego.com/news/health/20050812-9999-1n12liver1.html

(...)

"What we're finding in these patients is that there's so much fat in
their liver cells, the fat actually pushes the nucleus aside," said Dr.
Joel Lavine of UCSD, principal investigator for the San Diego portion
of an eight-center federal effort to study the disease in 1,600
children and adults. UC San Diego is recruiting about 200 people.

NASH is emerging rapidly on physicians' radar screens. The National
Institute of Diabetes and Digestive and Kidney Diseases, a funding arm
of the federal government, plans to spend $23 million during the next
seven years to learn more about the condition.<sniP>

^^^^^^

Ros and anti-ros,

http://www.nitrone.com/84/84rev.htm

I've done loads of these things. Sure CR makes less P. As well as
eating
nutrient dense functional foods and getting enough sleep and meditating
and doing many different things. But very few things makes a direct
impact on P pathways and those are the ones we need to work on.

^^^^^^^^^^^^^^^^^^^^
http://www.timesonline.co.uk/article/0,,8122-1731359,00.html

The burger and fags jab
Obesity and smoking-related diseases might soon be beaten by a shot in
the arm. Sam Lister reports

To all but the most rigid of disciplinarians, fighting the flab and the
fags are two of the great health trials of modern life. They can demand
years of willpower, puritanical diets, faddish patches and pills. Too
often the expenses are great and the rewards frustratingly small.

But imagine if the addictive pleasures of a cheeseburger and chips or a
quick cigarette could be countered and cured with a simple shot in the
arm. If some scientists are to be believed, the good times are fast
approaching for people with bad habits. Within the next five years
billions of pounds will be pumped into developing therapeutic vaccines:

(...)

Vaccines to combat conditions such as Aids and neurological diseases
are in development, while companies such as Cytos are also focusing on
chronic conditions. It is exploring vaccines for hypertension,
arthritis, asthma, psoriasis and osteoporosis, all of which work by
inhibiting the action of genes and hormones that help to spark off
conditions.

********

A vaccine for P would be nice. Or one that causes our bodies to make
more IL-10
would do the same thing most likely.

so?

randall.... doing those things over and OVER

randall

unread,

Aug 18, 2005, 6:52:31 PM8/18/05

Hi,

Hooray for Dr. Bowcock,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16106058
Understanding the Pathogenesis of Psoriasis, Psoriatic Arthritis, and
Autoimmunity via a Fusion of Molecular Genetics and Immunology.

Bowcock AM.

Divisions of Human Genetics and Dermatology, Departments of Genetics,
Pediatrics, and Medicine, Washington University School of Medicine, St.
Louis, MO.

The goal of my laboratory is to understand the molecular genetics basis
of the inflammatory skin disease psoriasis and associated psoriatic
arthritis. In performing these studies my colleagues and I have begun
to identify common pathways leading to autoimmunity as well, because
some of the defective pathways leading to autoimmunity are the same in
different autoimmune diseases. Some of these pathways are involved in
determining the activation status of inflammatory cells in the resting
state. Other pathways are likely to determine target organ specificity
and will be unique to a particular disease. Our approaches rely on
genetic studies with cases and families to identify the causative
variants, and then functional studies to identify the role of these
variants in the predisposition to psoriasis and autoimmunity. The
advantage of genetics approaches to understanding diseases such as
those of the immune system is that one can identify novel genes and
pathways that were not previously suspected as being involved in either
the immune system or tolerance.

PMID: 16106058

Sigh for Dr. Ann Brown and her kukui nuts in paradise,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16101874

Skin cells take on a larger role in inflammation,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16101542
Although in the past, keratinocytes were considered simply as passive
targets of immunological attack from infiltrating T lymphocytes, a
number of studies have definitively demonstrated that keratinocytes
actively participate in the cutaneous immune responses. Upon
activation, keratinocytes express a plethora of cytokines, chemokines
and accessory molecules, which can transmit both positive and negative
signals to cells of innate and adaptive immunity. Dysregulation and
abnormal expression of inflammatory mediators or their receptors in
keratinocytes are relevant to the pathogenesis of chronic inflammatory
skin diseases such as psoriasis, atopic dermatitis and allergic contact
dermatitis.

PMID: 16101542

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16100459
Defensins and cathelicidins (LL-37) are major antimicrobial peptides
(AMPs) of the innate immune system of the human skin. In normal
non-inflamed skin these peptides are negligible, but their expression
can be markedly increased in inflammatory skin disease such as
psoriasis. We designed this study to identify the expressions of LL-37
in normal human keratinocyte (NHK) and HaCaT cells after exposure to
stimulants and to investigate difference of LL-37 expression
accompanied with cell differentiation status, and come to understand
difference of susceptibility to infection in atopic dermatitis and
psoriasis. Expressions of LL-37 in NHKs and HaCaT cells were evaluated
by using RT-PCR, Western blotting, and immunohistochemical (IHC)
staining at 6, 12, and 24 hr post stimulation after exposure to
Ultraviolet B irradiation and lipopolysaccharide. And expression of
LL-37 in skin biopsy specimens from patients with atopic dermatitis and
psoriasis was determined by immunohistochemical analysis. In
time-sequential analyses of LL-37 expression revealed that LL-37 was
expressed in NHKs, but not in HaCaT cells. IHC analysis confirmed the
presence of abundant LL-37 in the epidermis of psoriasis. Therefore we
deduced that expression of LL-37 is affected by UV irradiation,
bacterial infection, and status of cell differentiation.

PMID: 16100459

More on skin and stem cells to comtemPlate.

http://www.newscientist.com/article.ns?id=dn7856
A gene which appears to be a "master control gene for the skin" may
hold the key to youth, suggests a new study in mice. The finding could
lead to breakthroughs in anti-ageing strategies, skin care and even
chemotherapy.

The gene p63, a sister gene to the cancer suppressing p53 gene, was
found to accelerate ageing in adult mice when it was "switched off"
by researchers.

Mice which had the gene completely switched off using a sophisticated
genetic technique, suffered premature ageing. Symptoms included
becoming hunchbacked, losing hair and losing weight. Loss of p63 also
cut short their lives - by about 23% - compared with mice with
normal p63 expression.

The gene may shed light on understanding the ageing process, says Alea
Mills, an assistant professor at Cold Spring Harbor Laboratory, US, who
led the study. "I absolutely think it will be key in trying to
understand what to avoid," she says, for example in investigating the
link between UV light and ageing.

Cancer risk
The finding may also help scientists understand and, in the future,
treat ageing caused by some medical treatments. "Certain chemotherapy
has a really striking effect on the skin and features of accelerated
ageing, such as hair loss. Some of these treatments are probably
impacting on the p63 pathway," she notes.

"There might be great things we can do to keep our skin looking
healthy and young looking," she told New Scientist. But she cautions
that previous studies have shown that too much p63 can lead to cancer,
so a "fine balance" needs to be struck.

The gene is structurally similar to p53, which is a crucial gene in
suppressing cancer. A loss of p53 can lead to the development of
tumours. Mills and her team initially set out to see what happened to
mice deficient in p63 - with one good and one defective copy of the
gene - as they aged. They suspected they might suffer more tumours,
but found none. "There aren't tumours, but they aged
prematurely," she told New Scientist.

They then developed a way of completely shutting down the gene in
specific tissues, such as the skin, of adult mice. This caused specific
features of accelerated ageing.

Mills says the p63 gene is very similar between humans and mice. "We
think that p63 is likely to play a fundamental role in maintaining
human skin as well." She says the team would like to examine how p63
expression changes during normal human ageing.

^^^^^^

http://www.signonsandiego.com/news/science/20050817-9999-lz1c17cells.html
Stem cells promise medical miracles, but there's a dark side, too

Human stem cells boast a kind of immortality. They are able to
precisely copy themselves, over and over, for our entire lives.

We shed and regrow our outer layer of skin cells once every 27 days or
so - roughly 1,000 new skins in the average lifetime. But the stem
cells from which those outer skin cells originate are essentially the
same ones we were born with - and the same ones with which we will
die.

It's this enduring quality, combined with their remarkable ability to
develop into almost any kind of cell needed, that has elevated stem
cells to iconic medical marvel, the means one day of perhaps repairing
- even regenerating - tissues and organs damaged and destroyed by
disease, accident and age.

But there's a dark side to this power of self-renewal. It's called
cancer. And evidence grows daily that many - if not all - types of
cancers are the consequence of normal stem cells gone bad.

"To use a Star Wars analogy, it's Jedi Knights and Darth Vader," said
Dr. Evan Snyder, director of the Stem Cells and Regeneration Program at
the Burnham Institute in La Jolla. "Normal stem cells have these
amazing powers to differentiate into other cells, to move about the
body, to go where they're needed. Cancer stem cells have the same
skills, but they use them for evil."

Think of cancer as a disease of uncontrolled self-renewal, said
Tannishtha Reya, an assistant professor of pharmacology and cancer
biology at Duke University. Normal stem cells renew themselves under
precise and carefully regulated conditions so their progeny are exactly
what is intended and needed. Cancer stem cells do not. They simply grow
amok, producing countless lesser copies that corrupt and may eventually
kill. A tumor is, in this sense, really just an aberrant organ.

For decades, researchers have focused on treating cancer through
reduction. If a therapy killed cancerous cells, if it reduced the size
of a tumor, it was deemed a success. Clinical trials to test new cancer
drugs were - and are - largely based on how well they reduce the
number of detectable cancer cells or shrink tumors.

<sniP>

randall... be well

randall

unread,

Aug 20, 2005, 2:05:55 PM8/20/05

Hi,

The P news from google isn't floating my attention or boat these last
few days.

Off to pubmed instead.

What do you do when your biological isn't logical? And you have a flare
uP?
Double down!

RaPtiva the double down- rebound anti-flare prescription? Get the
point?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16109173
Psoriasis vulgaris flare during efalizumab (raptiva) therapy does not
preclude future use: a case series.

Lowes MA, Turton JA, Krueger JG, Barnetson RS.

BACKGROUND: Severe psoriasis vulgaris can be extremely difficult to
treat in some patients, even with the newer biological therapies
available today. Case presentation. We present two patients with severe
chronic plaque psoriasis who received numerous systemic anti-psoriatic
therapies with varied results. Both responded well to initial treatment
with efalizumab (anti-CD11a), but then experienced a flare of their
disease after missing a dose. However, after disease stablization, both
patients responded well to re-introduction of efalizumab, one patient
requiring concurrent treatment with infliximab (anti-TNF-alpha).
Conclusions. These cases are presented to characterize this "flare"
reaction, and to inform health care providers that efalizumab can still
be administered after disease flare, and again may be a successful
therapy.

PMID: 16109173

We should make them pay us twice the price for any nasty flare uPs!
That won't work. I can see the $ hungary tyPes shooting uP interferon
now.

Possible new topical agent.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16109743
BP-1107: A Novel, Synthetic Thiazolidinedione that inhibits epidermal
hyperplasia in Psoriatic skin - SCID Mouse transplants following
topical application.

Bhagavathula N, Nerusu KC, Reddy M, Ellis CN, Chittiboyina A, Avery M,
Pershadsingh HA, Kurtz TW, Varani J.

University of Michigan.

Recent studies have demonstrated that orally administered
thiazolidinedione ligands of the peroxisome proliferator-activated
receptor-gamma (PPAR-gamma) can ameliorate clinical features of
psoriasis in humans. Thiazolidinediones also inhibit the proliferation
of psoriatic keratinocytes in monolayer and organ culture, and at least
one of these agents (troglitazone) inhibits epidermal hyperplasia of
human psoriatic skin transplanted to severe combined immunodeficient
(scid) mice. In the present study we show that a novel, synthetic,
thiazolidinedione derivative (BP-1107) is capable of inhibiting
psoriatic hyperplasia in the scid mouse transplant model after topical
application. Like other thiazolidinediones, BP-1107 inhibits
proliferation of rapidly growing keratinocytes in monolayer culture,
but compared to these agents, the effective dose of BP-1107 needed to
suppress keratinocyte proliferation is much lower. Concentrations of
BP-1107 that effectively inhibit keratinocyte function have no
detrimental effect on dermal fibroblasts. These data suggest that
effective topical anti-psoriatic therapy may be provided with this
agent.

PMID: 16109743

Ok, i know what your gonna say. This worked on SCid mice with fake P
and
we're miles from that deal.

Any dream in a port?

Interferon treatment induces psoriasis at the puncture point.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16109199
[Activation of psoriasis in patients undergoing treatment with
interferon]

[Article in Danish]

Navne JE, Hedegaard U, Bygum A.

Odense Universitetshospital, Dermato-venerologisk Afdeling I, og
Laegemiddelinformationscentralen, Afdeling KKA.

Psoriasis is a chronic, inflammatory skin disorder that is induced and
aggravated by a number of endogenous and exogenous factors.
Traditionally lithium, beta blockers, NSAIDs, ACE inhibitors and
antimalarials have been associated with psoriasis, but interferon can
also be a triggering factor. We present two patients with multiple
sclerosis who suffered from activation of psoriasis in relation to
interferon-beta treatment. In one of the patients, psoriasiform
injection site lesions persisted six years after termination of the
interferon treatment.

PMID: 16109199

Some day, a toPical that acts like a biological would be nice.

randall... new reasons to be afraid of needles.

randall

unread,

Aug 23, 2005, 5:30:05 PM8/23/05

Hi,

Pubmed time again. The regular P news is broken. Either that or my
ability to read it. lol

This one got my attention. A new cePt from BM/S.

But how new? And who knew? Kim does!

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16113966
BMS-188667 (Bristol-Myers Squibb).

Dumont FJ.

Department of Immunology, Room RY80W107, 126 East Lincoln Avenue, PO
Box 2000, Merck Research Laboratories, Rahway, NJ 07065, USA.
francis...@merck.com.

Bristol-Myers Squibb is developing CTLA4-Ig, an immunosuppressant
immunoglobulin, for the potential treatment of various immunological
disorders, including graft versus host disease, lupus erythematosus and
psoriasis. A phase II trial has commenced for psoriasis [261944]. The
compound is also in development for inflammation, rheumatoid arthritis
and allergy [204704,261944]. A collaboration with Genzyme Transgenics
covers the following indications: psoriasis; organ transplant
rejection; and several autoimmune disorders [261944].

PMID: 16113966

Is, or was there an enbrel litigation thing going on here with BM?

http://www.repligen.com/content.php?page_id=16&PHPSESSID=c0678bc7601ea84824cdbee203c449cd
(...)

CTLA4-Ig for Autoimmune Disorders
Repligen owns the exclusive rights to an issued U.S. patent that covers
the use of CTLA4-Ig for the treatment of various autoimmune diseases
including rheumatoid arthritis and multiple sclerosis. This patent will
remain in force until 2021 and also covers a method of treating
rheumatoid arthritis, multiple sclerosis, lupus and scleroderma with
CTLA4-Ig alone and in combination with other immunosuppressant drugs.
Additionally, we own the exclusive rights to a European patent with
substantially similar claims that will remain in force until 2013.
Repligen owns the exclusive rights to these patents through a license
agreement with the University of Michigan and through a Cooperative
Research and Development Agreement with the United States Navy. These
patents are independent of the patents on CTLA4-Ig that were the
subject of a lawsuit that Repligen and the University previously
prosecuted against Bristol-Myers Squibb Corporation.

Bristol-Myers Squibb Corporation presented positive results from two
Phase 3 clinical trials of their form of CTLA4-Ig at the annual meeting
of the American College of Rheumatology in October 2004. Bristol has
disclosed that they completed filing a New Drug Application for
CTLA4-Ig in rheumatoid arthritis in March 2005. The FDA has granted
CTLA4-Ig (AbataceptTM) Fast Track Designation. Bristol anticipates
launching AbataceptTM by the end of 2005.
http://www.repligen.com/content.php?page_id=43

AbatacePt? How about abracadabra-cept? But like with magic, its still
not really gone!

The rabbit is down his pants or under the table. yikes

Could the magic be how the scientists jump around these pharma's?
http://www.medadnews.com/News/Index.cfm?articleid=265184

Trade secrets hoP around like mexican jumPing beans. No wonder there's
litigation going on.

But, we the patients, you know those that suffer, don't gives a rat's
rear end. We want more
better durgs and lower prices. So there.

Moving on. Another mini randall rant...

What's in the P NG (psoriasis newsgroup)
http://groups-beta.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=CTLA4-Ig&qt_g=1&searchnow=Search+this+group

Kim's thread from 1997 is quite good to give a layman's perspective.
(Aren't we all...lol)

Once all the P pathways are known and explained by Dr. Bowcock or some
other scientist, then we'll have an exPerts exPlanation for P.

A search of all groups shows the far ranging consequences of a drug
that can BLOCK the immune
system,
http://groups-beta.google.com/groups?q=CTLA4-Ig&qt_s=Search

Block the Dock,
http://www.wehi.edu.au/media/images/fig6.gif
from here: http://www.wehi.edu.au/research/overview/atd.html

We all are just sitting on the dock of the bay. P wise.

Now that the seals have taken over in SF, we just need to find our
seals.
They just can't be left to block all the piers, docks etc. Only those
antigens
from THE SUPERANTIGEN/ANTIGEN etc.

More docks,
http://arthritis-research.com/content/7/Suppl+2/S15/figure/F3?highres=y
http://www.thieme-connect.com/bilder/sth/200301/sth00856.02

Lets look further,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15967784
A minor population of splenic dendritic cells expressing CD19 mediates
IDO-dependent T cell suppression via type I IFN signaling following B7
ligation.

Baban B, Hansen AM, Chandler PR, Manlapat A, Bingaman A, Kahler DJ,
Munn DH, Mellor AL.

Immunotherapy Center and.

By ligating CD80/CD86 (B7) molecules, the synthetic immunomodulatory
reagent CTLA4-Ig (soluble synthetic CTLA4 fusion protein) induces
expression of the enzyme indoleamine 2,3-dioxygenase (IDO) in some
dendritic cells (DCs), which acquire potent T cell regulatory functions
as a consequence. Here we show that this response occurred exclusively
in a population of splenic DCs co-expressing the marker CD19. B7
ligation induced activation of the transcription factor signal
transducer and activator of transcription (STAT1) in sorted CD19+, but
not CD19(NEG), DCs. STAT1 activation occurred even when DCs lacked
receptors for type II IFN (IFNgamma); however, STAT1 activation and IDO
up-regulation were not observed when DCs lacked receptors for type I
IFN (IFNalphabeta). Thus, IFNalpha, but not IFNgamma, signaling was
essential for STAT1 activation and IDO up-regulation in CD19+ DCs
following B7 ligation. Consistent with these findings, B7 ligation also
induced sorted CD19+, but not CD19(NEG), DCs to express IFNalpha.
Moreover, recombinant IFNalpha induced CD19+, but not CD19(NEG), DCs to
mediate IDO-dependent T cell suppression, showing that IFNalpha
signaling could substitute for upstream signals from B7. These data
reveal that a minor population of splenic DCs expressing the CD19
marker is uniquely responsive to B7 ligation, and that
IFNalpha-mediated STAT1 activation is an essential intermediary
signaling pathway that promotes IDO induction in these DCs. Thus, CD19+
DCs may be a target for regulatory T cells expressing surface CTLA4,
and may suppress T cell responses via induction of IDO.

PMID: 15967784

Looking at IDO (indoleamine),

http://www.medicalnewstoday.com/medicalnews.php?newsid=24617

This link may exPlain the trytophan thing awhile back. Comments?

(...)

The transmitter is indoleamine 2,3-dioxygenase, or IDO, an enzyme
particularly expressed in places such as the gastrointestinal tract and
tonsils where the immune system routinely meets up with foreign
substances it might want to ignore.

Drs. Munn, Andrew L. Mellor and Simon J. Conway published a Science
article in 1998 showing IDO's role in protecting the fetus from
rejection by the mother's immune system during pregnancy. Later they
learned that tumors and persistent viruses such as HIV may hijack this
mechanism to shield themselves from immune attack.

They knew IDO degraded tryptophan, an amino acid essential to the
survival of T cells. They weren't so certain what happened at the
receiving end.

The researchers wondered if T cells exposed to IDO might simply starve
to death without enough trytophan, one of nine essential amino acids
attainable only through food. "If the T cells are just starving, then
you don't need a receiver. They just die. But the T cells didn't seem
to be dying. They seemed to be rendered selectively non-responsive,"
says Dr. Munn. "That sounded more like the T cell was participating
in this process."

So the researchers started looking at the few genes known to respond to
amino acid levels and found GCN2.

GCN2 is present and active in many cells, but its major sites of action
are unknown and its role in T cells was unexplored, Dr. Munn says.
"GCN2 is a nutrition sensor in yeast," says Dr. Munn. GCN2 helps
yeast know when it has sufficient nutrition to grow; bread keeps rising
until yeast run out of nutrition. A paper published in March in Science
explores GCN2's role in mammalian survival by enabling mice to sense
they need to eat a well-balanced diet to stay healthy.

Dr. Munn contacted Dr. David Ron, a professor of medicine and cellular
biology at New York University School of Medicine's Skirball Institute,
studying the nutritional aspects of the gene. Dr. Ron, a co-author on
the Immunity paper, shared a GCN2 knockout mouse he developed and
helped the MCG researchers study the gene's role in T cells.

When these knockout mice were exposed to IDO, their T cells simply
ignored it.

The researchers had found a receiver and possibly more.

"No one had known any gene specifically targeted by IDO, and now we
have one," says Dr. Munn. "We had not known how T cells were turned
off. We didn't know if the T cells just were never activated, or if
they were actively suppressed by IDO. They all look like resting T
cells. Now we do know that there are differences."

MCG researchers want to know more about how GCN2 puts T cells to sleep.
"Whatever it's doing doesn't appear to be killing the T cells. It
would be nice to be able to mimic the effect of IDO by using a drug
that activates this pathway." Now that they have a knockout,
comparative studies with regular mice can determine other genes that
might be impacted downstream of GCN2.

Another big question is whether T cells deactivated by this system can
be reactivated. Knowing the role of the GCN2 gene makes it easier for
scientists to watch what happens to the T cells affected by IDO in a
living organism.
"We know that IDO itself is an important pathway. Evidence is
emerging that IDO seems to contribute to several important regulatory
processes in the immune system," Dr. Munn says of findings from labs
across the country. "But there has been a question in the field about
how the IDO expressed in one cell can signal to neighboring T cells.
Here's our first evidence of one way it may do so. By giving you a
target in the T cell that IDO is talking to, it helps you understand
the system better and we think it also may give us another target for
drugs to try to intervene in the system."

(This last story and link was posted one time previously in the P ng.)

^^^^^^^^^^^

Back to P.

Is it a yeast or fungus in the gut? A simple endotoxin (LPS) from one
of them?

I'll need more time to dig deePer.

randall.. on the deeP end of the P ocean

randall

unread,

Aug 26, 2005, 12:31:48 PM8/26/05

Hi,

Musician and celebrated guitarist Shawn Lane.
http://www.memphisflyer.com/gyrobase/Content?oid=oid%3A9997

(...)
He also suffered from severe arthritis, psoriasis, and other
immune-system problems, which left him in great pain and made it
difficult for him to practice his music. He quit watching his diet and
began to struggle with his weight, which exceeded 300 pounds.

(...)

Musician Bill Oliver, for his part, misses the friend he knew since
childhood.

"Shawn was one of those genius, madness people. ... But my fondest
memory of him is his laugh. He was a lover of things, not a hater,"
Oliver says. "He associated music with happiness. In every other part
of his life, there was tragedy." <sniP>

*****

Earthbound skin care for p

http://www.pressbox.co.uk/detailed/Health/Psoriasis_Skin_Care_Help_34896.html

*******

If you read the first story,
http://www.health24.com/Woman/General/711-733-1497,32997.asp
(...)

A review article published online in the journal BMC Dermatologyin
April 2004 concluded that, "Skin conditions may be a significant
problem not only in professional instrumentalists, but also in
musicians of all ages and ability. Although not life-threatening, they
may lead to impaired performance and occupational hazard." Playing an
instrument can aggravate existing skin conditions like atopic eczema
and psoriasis.<sniP>

**********

Over to pubmed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16117788

Topical Application of A Novel Immunomodulatory Peptide, RDP58, Reduces
Skin Inflammation in the Phorbol Ester-Induced Dermatitis Model.

De Vry CG, Valdez M, Lazarov M, Muhr E, Buelow R, Fong T, Iyer S.

Department Discovery Research, Sangstat Medical Corporation, Fremont,
California, USA.

RDP58 is the first lead compound in a series of immunomodulating
decapeptides discovered through activity-based screening and
computer-aided, rational design. RDP58 disrupts cellular responses
signaled through the Toll-like and tumor necrosis factor (TNF) receptor
families and occludes important signal transduction pathways involved
in inflammation, inhibiting the production of tumor necrosis factor
alpha (TNFalpha), interferon-gamma, interleukin (IL)-2, IL-6, and
IL-12. These pro-inflammatory cytokines are thought to be involved in
the pathogenesis of several inflammatory and autoimmune diseases,
including atopic dermatitis and psoriasis. The goal of this study was
to determine the ability of RDP58 to inhibit skin inflammation
following exposure to the well-characterized protein kinase C activator
and tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical
application of RDP58 to the epidermis following TPA treatment resulted
in the amelioration of the phorbol ester-induced irritant contact
dermatitis. Substantial reductions were observed in skin thickness and
tissue weight, neutrophil-mediated myeloperoxidase activity,
inflammatory cytokine production, and various histopathological
indicators. We also found RDP58 to be effective in reducing the
compounding inflammatory damage brought on by chronic TPA exposure, and
that it is capable of targeting inflammatory mediators specifically in
the keratinocyte. These results demonstrate that topically applied
RDP58 is an effective anti-inflammatory treatment in the phorbol
ester-induced dermatitis model, and suggest that it may have
therapeutic potential in a variety of immune-related cutaneous
diseases.

PMID: 16117788

What's RDP58? Like brew 102?

Let's look,
http://www.cyperus.com/cgi-bin/stories.pl?ACCT=105&STORY=/www/story/04-28-2003/0001935324

RDP58
SangStat completed initial Phase II studies of RDP58, its potent
anti-inflammatory peptide, in the first quarter of 2003 in both
ulcerative
colitis (UC) and Crohn's disease. The preliminary results of the Phase
II
studies of RDP58 at 100mg, 200mg and 300mg per day in UC and Crohn's
were
released on April 9, 2003. The Phase II studies of RDP58 demonstrated
a peak
response rate of 77 percent and a 71 percent remission rate among
patients
with ulcerative colitis taking 200mg/day of active drug. Patients with
ulcerative colitis who received 300mg/day of RDP58 achieved similar
response
and remission rates. Overall, both the response and remission rates
were
statistically significant. In Crohn's disease, although 66 percent of
patients treated with 200mg/day of RDP58 achieved a response, the study
did
not yield a statistically significant dose response. SangStat believes
that
additional analysis and clinical studies using higher dosing and longer
administration may be needed to determine efficacy in Crohn's disease.

Does something in the gut,
http://ard.bmjjournals.com/cgi/content/abstract/61/suppl_2/ii19

And does it to TNF down there,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12795464&dopt=Citation
BACKGROUND: Tumour necrosis factor (TNF) plays a key role in the
pathogenesis of Crohn disease (CD). RDP58 is a novel anti-inflammatory
decapeptide which was developed using a novel rational design strategy.
Recently, RDP58 has proved to be a potent inhibitor of TNF production
at a post-transcriptional step. The aims of this study were to
investigate the anti-inflammatory properties of RDP58 ex vivo in human
CD and in vivo in an experimental model colitis. METHODS: Biopsies and
lamina propria mononuclear cells from inflamed colonic mucosa of 18 CD
patients were cultured for 24 h in the presence or absence of RDP58.
TNF was quantified in a bioassay: interferon (IFN)-gamma and
interleukin (IL)-1beta levels were measured by enzyme-linked
immunosorbent assays. Colitis was induced by intra-rectal
administration of 2, 4, 6 trinitrobenzene sulphonic acid (TNBS) in
rats. Inflammation was assessed following 7 days of oral therapy with
RDP58 or vehicle alone. RESULTS: RDP58 led to decreased TNF and
IFN-gamma (but not IL-1beta) production by biopsies and lamina propria
mononuclear cells from CD patients. In rats with TNBS-induced colitis,
oral RDP58 therapy reduced weight loss and diarrhoea and improved
macroscopic and histological inflammation scores. CONCLUSIONS: Our
results suggest that RDP58 may be an effective therapy for CD with the
clinical advantage of an oral administration.

PMID: 12795464

And may even fix uP your oral cavity on the way down, (blocks LPS)
http://iadr.confex.com/iadr/2004Hawaii/techprogram/abstract_39019.htm

And from a group hit (search RDP58, 12 hits)
RDP58 - The Lead in a New Family of Compounds
SangStat's approach to the development of new, more potent
anti-inflammatory
peptides is based on the knowledge that inflammation results from
complex
biological events. The lead compound to emerge from this new family of
drugs, called rationally designed peptides (RDP), is RDP58.
RDP58 inhibits the synthesis of tumor necrosis factor alpha (TNFa),
interferon gamma (INFg), and IL-12. These cytokines are often elevated
in
autoimmune disorders and are important in the activation of immune
responses
and inflammation. RDP58 also upregulates heme oxygenase (HO-1) in vivo.
Up-regulation of HO-1 has been associated with inhibition of
inflammation.
SangStat believes that RDP58 is a platform molecule with multiple
potential
applications.
Currently SangStat's discovery research team is working to create next
generation peptides. With the discovery of new compounds, SangStat
hopes to
improve potency, enhance bioavailability and develop novel cytokine
inhibitors.

randall... thinking he likes rationally designed PePtides.. why 58?

JXStern

unread,

Aug 26, 2005, 10:38:21 PM8/26/05

was: P News

Why not?

I keep hearing about these peptides, ought to be takeable orally or by
patch, even by ointment, come on guys, get one going here!

randall

unread,

Aug 27, 2005, 3:33:09 PM8/27/05

Good point.

> I keep hearing about these peptides, ought to be takeable orally or by
> patch, even by ointment, come on guys, get one going here!
>
> J.

I still feel that a IL-10 promoter in our guts is the secret sauce.

That lactobacillus that PooPs out IL-10 ought to do it. I hope
no one has to run 58 tests to figure that out. As long as the IL-10
strain of bugs doesn't do any harm, it may do a load of GOOD.

In pubmed the other day,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt«stract&list_uids 118714

Ilodecakin (schering-plough corp).

Marshall JK.

Division of Gastroenterology, Department of Medicine, Health Sciences
Center, Room 4W8, 1200 Main Street West, Hamilton, Ontario L8N 3Z5,
Canada. mars...@fhs.csu.mcmaster.ca.

Schering-Plough's interleukin (IL)-10 (ilodecakin) is under
investigation for the potential treatment of autoimmune diseases, solid
tumors, ulcerative colitis, Crohn's disease and organ transplantation
[174696,211855]. In June 1996, ilodecakin entered phase II trials for
Crohn's disease, ulcerative colitis and rheumatoid arthritis
[211855,281013] and, as of June 1999 was reported to be in phase III
trials for Crohn's disease and rheumatoid arthritis
[317542,319539,329277]. It has also demonstrated promising effects in
the treatment of inflammatory bowel disease [309573]. In January 1997,
phase I trials began in HIV-infected patients. Initial results from a
pilot study, carried out by the National Institute of Allergy and
Infectious Disease Control, indicated that a single dose of IL-10
decreases the blood viral load. The results, however, were transient
[237334]. Early clinical studies are ongoing in acute lung injury,
ischemia-reperfusion injury, multiple sclerosis and psoriasis [281013].
In February 1999, Morgan Stanley Dean Witter predicted sales of US $50
million in 2000 rising to US $325 million in 2005 [317542].

PMID: 16118714

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=eurekah.section.22630
(...)

In our pilot trial starting in 1997, daily injections of 8 ?g rhIL-10
/kg body weight directly under a psoriatic plaque over a 24 day period
led to complete clearance of the plaque in one of two patients. 5
Moreover, some systemic antipsoriatic effects were observed in all 3
patients treated in this pilot trial (subcutaneous injections under
nonlesional skin in the third patient).

In a second trial (open-label phase II), ten psoriatic patients
received subcutaneously rhIL-10 over a 7 week period in a dosage of 8
?g/kg daily (n=5) or 20 ?g/kg three times per week (n=5), respectively.
11 Patients were followed up for an additional 7 weeks. The treatment
was well tolerated. We found antipsoriatic effects in 9 out of 10
patients resulting in a significant decrease of the psoriasis area and
severity index (PASI) by 55.3 ± 11.5 % (mean ± SEM, p<0.02). The
antipsoriatic effect was confirmed by histological examination.
Heterogeneity in the effec-tiveness was found among the patients, but
seemed to be independent of the dosage regime 11 (Fig. 2).

Similar clinical effectiveness of IL-10 application has been reported
by Reich et al.12 In this open-label phase II trial ten patients were
treated subcutaneously with 4 ?g/kg rhIL-10 daily. The mean of the
disease activity score PASI decreased by 67.9% after 6 weeks of
treatment and was associated with improvement of histological
parameters. 13 The clinical response was asso-ciated with a significant
decrease of cutaneous cell infiltration and the lesional expression of
type1 cytokines (IFNg, TNF), IL-17 IL-8, and IL-8 receptor CXCR2. There
was some evidence that genetic factors are involved in the response to
IL-10. 13
<snip>

Do they kill the rabbits to get this stuff? I don't mind colon flora
taking gas (dying) as the little buddies are so ubiquitious in a
thriving colony.

****

Il-10 is a good thing for psoriasis,

http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=il-10+il-19&qt_g=1&searchnow=Search+this+group

>From pubmed today.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16120148
Interleukin-19 upregulates keratinocyte growth factor and is associated
with psoriasis.

Li HH, Lin YC, Chen PJ, Hsiao CH, Lee JY, Chen WC, Tzung TY, Wu JC,
Chang MS.

Institute of Basic Medical Sciences, National Cheng Kung University,
no. 1 Ta-Hsueh Road, Tainan 704, Taiwan.

Summary Background Interleukin (IL)-19, a member of the IL-10 family,
signals through the IL-20R1/IL-20R2 heterodimer, which is shown to be
involved in abnormal keratinocyte differentiation and proliferation.
Little is known about its in vitro biological functions or its role in
psoriasis. Objectives To investigate the role of IL-19 in the psoriatic
process. Methods The expression of keratinocyte growth factor (KGF)
transcripts was measured by polymerase chain reaction in CD8+ T cells
treated with IL-19. Next, we developed monoclonal and polyclonal
antibodies to measure the levels of IL-19 in the sera of patients with
psoriasis and healthy volunteers using an enzyme-linked immunosorbent
assay. In addition, we performed immunohistochemical staining on
psoriatic skin and normal controls. Results We found that IL-19
upregulated KGF transcripts on CD8+ T cells. Patients with psoriasis
had a lower level of IL-19 in serum than healthy volunteers. The
difference between these two groups was statistically significant (P <
0.05). IL-19 expression was seen in basal and suprabasal keratinocytes
in a continuous pattern, and was increased in psoriatic epidermis.
Conclusions These results suggest that IL-19 plays a role in the
complex pathological cytokine network in psoriasis.

PMID: 16120148

&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

And if that doesn't do it for us soon enough, why can't we fall back on
the FAE's right now?

Talk about a rational drug. We could easily do the FAE's for the next
year or
so untill the really great good gut critters pass the FDA GRAS list.

>From pubmed today.

The stuff looks great on PaPer,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16120141
Fumaric acid esters for severe psoriasis: a retrospective review of 58
cases.

Harries MJ, Chalmers RJ, Griffiths CE.

The Dermatology Centre, The University of Manchester, Hope Hospital,
Stott Lane, Salford, Manchester, U.K.

Summary Background Fumaric acid esters (FAE) have been used to treat
severe psoriasis in northern Europe for over 20 years. A recent
systematic review has shown FAE to be an effective systemic treatment
for severe psoriasis. However, FAE remain unlicensed in the U.K.
Objectives To present data relating to the efficacy and tolerability of
FAE in severe psoriasis and report our experiences of FAE therapy at
one U.K. centre. Methods Patients who had received FAE for severe
psoriasis at one U.K. regional referral centre between June 1999 and
October 2003 were identified from pharmacy records. Their records were
analysed retrospectively. Results Fifty-eight patients (25 women, 33
men) were identified. Fifty-five (95%) of the 58 patients had
previously used other systemic antipsoriatic therapies with over 70%
previously using two or more agents. Thirty-two patients (55%) showed
improvement in their psoriasis with 10 (17%) being rated as 'clear' or
'virtually clear' by the attending physician. No improvement was seen
in 28% patients and 16% showed worsening of their disease. Adverse
events were common and were reported in 66% patients. These mainly
consisted of abdominal pain (61%), diarrhoea (55%), flushing (45%),
nausea (21%) and malaise (15%). They led to discontinuation of
treatment in 15 patients after a mean period of 4.7 months.
Lymphocytopenia developed during treatment in 57% of patients, all of
whom had had a baseline value within the normal range. In only one
patient was this considered severe enough to warrant withdrawal of
treatment. Conclusions Our study has shown that FAE are an effective
therapy in selected patients with severe psoriasis, even in those who
have previously been intolerant of systemic therapy or where it has
failed.

PMID: 16120141

randall... having a very nice day. My IP6 trial is going great guns.

randall

unread,

Aug 30, 2005, 4:30:24 PM8/30/05

Hi,

P news from around the World

Is coffee OK now?

http://www.geek.com/news/geeknews/2005Aug/gee20050830032072.htm

Geekish stigma or not, whats the psoriatics take on it?

Food flares are on everyone's radar at one time or another.

^^^^^^^^^^^^^^

Given enough time they may find something healthy with HCA's

http://www.suntimes.com/output/news/cst-nws-grilling30.html

Grill and flare on your menu to-nite?

Or is it the fats?

******

Which are the healthy fats for you?

http://www.knowledgeofhealth.com/pdfs/cookingoil.pdf

Using vitamin C to make more bile for lipid digestion has been the
next phase of my latest IP6 trails.

Evidence for that,

http://groups.google.com/group/misc.health.alternative/browse_frm/thread/9f3e0368d7b13fd9/2b2405ab84828d89?lnk=st&q=bile+vitamin+C&rnum=2#2b2405ab84828d89

> > I have had personal experience with vitamin c and cholesterol. Linus
> > Pauling was right, an intake of 3 or 4 grams per day keeps cholesterol
> > in check and it certainly beefs up the immune system. Anybody else
> > tried it?

> I take 3 grams of Ester C per day, and it did nothing for my
> cholesterol counts. It did, however, help greatly with my
> predisposition to catching colds & bleeding gums...

"Not unusual to see a variable result. Ascorbic acid is used to convert

cholesterol to bile acids for excretion in bile. Increasing ascorbic
acid
intake can help improve bile acid formation but that does not
necessarily
mean that serum cholesterol will drop. Having something present in the
diet to help keep these bile acids from being actively reabsorbed
should
give a nice reduction in serum cholesterol levels (that material is
called
water soluble fiber).

Marty B. "

So?

Eat your fruits and veggies. At least five servings a day.

And try some insoluble fiber as well should you be bound up.

************

How sweet is sweet wormwood (Artemisia annua) for malaria?
http://www.hindustantimes.com/news/181_1473788,001100020006.htm

Trial of a drug derived from an ancient Chinese herb has been shown to
reduce the risk of death in malaria patients, says a study.

Researchers conducted trial of the drug artesunate derived from sweet
wormwood, or Artemisia annua, on malaria patients between June 2003 and
May 2005 and found a clear benefit over standard treatment of quinine
on them, according to a report in science portal EurekAlert.<sniP>

This wormwood stuff is used in the hulda clark recipe for curing all
dis-ease.

Does the worm turn for malaria patients taking it?

Looks so.

Lets look further.

Quinine comes from Chichona bark
http://www.agridept.gov.lk/NBG/H_cinco.htm

According to an article in The Times, a Chinese herb known as Qing Hao,
sweet wormwood or artemisia annua L. is being grown massively to help
end the reign of malaria, one of the major killer diseases in Africa,
which has become resistant to our standard quinine-based drugs

http://www.newmediaexplorer.org/sepp/2004/07/17/sweet_wormwood_heals_malaria.htm

The biggest problem I have with this is understanding why lithium and
quinine flare my psoriasis so fast.

Understanding these pathways will certainly aid us in fighting the P
battles.

And even may help win the P WAR soon.

*****

What if you could live longer? If researchers like Ann Bowcock are
looking
diligently at our P genes they may take notice of whether we have the
Klotho gene.

http://www.bestsyndication.com/2005/Dan-WILSON/Health/08/082705-Klotho-gene-hormone-aging.htm

Researchers at the University of Texas Southwestern Medical Center led
by Dr. Makoto Kuro-o (M.D., Ph.D.) found that a naturally occurring
hormone called Klotho extended the lifespan of mice up to 30%. They
also found that it increases the susceptibility to diabetes and
decreases fertility. The study was reported in the online journal
Science Thursday.

The hormone is produced in the kidney and brain but can leak into the
bloodstream. It is the leakage that helped the mice live longer, so it
appears. Researchers will be looking into whether people that live
longer have an surplus of this hormone in the blood.

An earlier mice study conducted by Dr. Kuro-o in 1997 found that mice
that lacked the hormone had significantly shorter life spans. They
found the mice developed ailments including hardening of the arteries,
thinning bones, withered skin, and weak lungs

The Texas team identified a small protein component peptide that the
so called Klotho gene produces. They were able to genetically engineer
normal mice by injecting them with this purified peptide. The
genetically engineered male mice lived 31% longer than normal males.
The modified females lived 19% longer.

The team noticed the hormone increased the body?s resistance to
insulin. Previous studies have shown this condition correlates to an
extended life span. Ultra-low calorie diets also increase insulin
resistance.

Experiments involving cells in the laboratory indicated the peptide
substance modulates a crucial biological pathway involving basic
metabolic functions. It is interesting that the mice did not have an
increased level of glucose in their blood which is a primary symptom of
diabetes.

Other studies found that ?damping down? this insulin/insulin-like
growth factor-1 signaling pathway may be the same mechanism that
extends longevity in animals that were fed ultra-low calorie diets.
Previous research found that people with a certain variation of the
gene are prone to age related diseases like heart attacks, strokes and
osteoporosis.

Klotho is named after one of the Greek Goddesses who spins the thread
of life controlling the longevity of individual humans. It is hoped
that this could lead to drugs that increase human life spans.

^^^^^

More of the same,
http://www.azcentral.com/news/articles/0825longevity-ON.html
&
klotho
http://www.kentucky.com/mld/kentucky/news/12490969.htm

*******

Our P DNA resarcher angel in Saint Louis, (Ann Bowcock)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16124855
The genetics of psoriasis and autoimmunity.

Bowcock AM.

Department of Genetics, Washington University School of Medicine, St.
Louis, Missouri 63110; email: bow...@genetics.wustl.edu.

Psoriasis is an inflammatory/autoimmune disease and, as with many
autoimmune diseases, is associated with alleles from the major
histocompatibility complex (MHC). With psoriasis and autoimmune
disease, the penetrance of the MHC-associated alleles is never 100%,
even for monozygotic twins. This may be because development requires
additional environmental and/or genetic modifiers or requires specific
T-cell receptor arrangements. Families segregating single or multilocus
susceptibility alleles other than the MHC have also been reported.
Overlapping genetic locations of loci for different autoimmune diseases
have been known for several years and are starting to reveal common
genes or genetic variants. These include genes normally involved in
preventing spontaneous T-cell activation or proliferation, immune
synapse formation, or cytokine production via pathways such as those
mediated by NFkappaB and those involved in thymic selection.
Autoimmunity may also involve dysregulation of genes or pathways
regulated by the RUNX family of transcription factors. RUNX is involved
in hematopoietic cell development, development of T cells in the
thymus, chromatin remodeling, and gene silencing. Hence, its effect on
cells of the immune system may be due to variable changes in gene
expression and could account for variable body surface involvement and
waxing and waning of disease.

PMID: 16124855

Ann has worked with the NPF tissue bank in the past.

SuPPort the NPF please. Join today.

*************************************************

>From current abstracts on pubmed...

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16127005
Chemokine receptors: attractive targets for drug discovery.

Godessart N.

Department of Biology, Almirall Research Center, Cardener 68-74, 08024
Barcelona, Spain. ngod...@almirall.es.

Studies of two antibodies, efalizumab and natalizumab, have recently
demonstrated that the blockade of leukocyte migration is of therapeutic
benefit for the treatment of diseases such as psoriasis and multiple
sclerosis. The role of chemokines in the control of cell traffic led to
their receptors being considered one of the most promising family of
targets aimed at disrupting cell recruitment in chronic inflammatory
processes. Choosing the appropriate chemokine receptor for each disease
was not easy, and the interpretation of target validation studies
proved to be extremely difficult. Despite an intense effort in the
search for chemokine receptor antagonists in the last decade, no
compounds in advanced clinical trials exist as such. The inherent
complexity of the family, the differences between the chemokine system
in mice and men, and the species selectivity of small-molecule
compounds could account for this fact. Pharmaceutical companies still
believe in chemokine receptors as therapeutic targets, as demonstrated
by the number of compounds reported to be in development. In the next
years, the developmental progression of these compounds will reveal
which target within the chemokine family is of real therapeutic value.

PMID: 16127005

If Ace is the place and is an issue in your P situation. You may need
an
ACE inhibitor.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16124358
Angiotensin-II behaves as an endogenous pro-inflammatory molecule.

Das UN.

UND Life Sciences, 1083 Main Street, Walpole, MA 02081, USA.

Angiotensin-II regulates vascular tone, stimulates the release of
pro-inflammatory cytokines, activates NF-kappaB, increases oxidant
stress, and suppresses nitric oxide synthesis, and thus, it functions
as an inflammatory molecule. Since ACE is present in many tissues, this
suggests that angiotensin-II may play a significant role in
atherosclerosis, congestive cardiac failure, stroke, bipolar disorder,
schizophrenia, dementia, Alzheimer's disease, psoriasis, atopic and
non-atopic dermatitis, eczema, several acute and chronic inflammatory
diseases, and cancer, conditions in which inflammation is an
aetiopathogenic factor. Thus, ACE inhibitors and/or angiotensin-II
receptor blockers could be of benefit in these conditions. Furthermore,
structural analogues of ACE inhibitors and angiotensin-II receptor
blockers could be developed that possess anti-inflammatory actions
without significant action on the cardiovascular system.

PMID: 16124358

randall... the mundane P news is now over and the genes carry on.

randall

unread,

Sep 1, 2005, 12:00:32 PM9/1/05

Hi,

P news selected by me. :)

Hey CoPPer! How about a little PePtide tonight?

Ok Mam, pull your skin over to the curb.

Yikes. Get the coPPer stat!

http://www.labtechnologist.com/news/news-ng.asp?n=62216-photomedex-copper-peptide-skin-disorders
31/08/2005 - PhotoMedex has announced it has received two US patents
covering the use of its copper peptide compounds in dermatological skin
disorders. The technology is set to have uses for a variety of active
agents, including active drug substances and promotes the use of copper
peptides as a viable therapy.

Copper is known to have many beneficial biological applications,
including wound healing, treating inflammatory conditions, and
effecting cosmetic improvements by, for example, stimulating a variety
of processes related to skin, such as collagen, elastin and
glycosaminoglycan production.

Copper salts alone are ineffective, or even inhibitory, for such
applications. The copper must be delivered in a biologically acceptable
form. As an example, when copper is complexed with a biologically
acceptable carrier molecule, such as a peptide, it may then be
effectively delivered to cells to provide beneficial biological
applications

The patent 6,927,205, refers to the treatment of a dermatological
condition related to psoriasis and details the topical application, a
composition comprising of at least one peptide copper complex to an
area of affected skin.

It has been found that such compositions, when topically applied, can
substantially diminish the signs and symptoms of psoriasis.

Thus, while there are a number of treatments for psoriasis currently
available, they all are accompanied by various side effects, high
costs, and long complicated treatment protocols.

Patent 6,927,206, refers to the treatment of rosacea, by topical
application of a composition also comprising a peptide copper complex.

Treatments for rosacea commonly involve topical or oral antibiotics
such as metronidazole and compounds such as sulfacetamide, sulphur, and
azelaic acid. However, these and the other treatments for rosacea that
are currently available, are all accompanied by various side effects,
are costly, and/or involve long complicated treatment protocols.

These patents issued are from a series of patents that had been
previously filed by ProCyte Corporation and are currently in the review
process covering new applications and combinations of the GHK and AHK
copper peptides and other metallic peptides.

"The newly issued patents add to our intellectual property base and
provide new avenues to explore individual and/or combination therapies
that may accelerate or in other ways improve existing treatments in
dermatology that could lead to better patient results," said PhotoMedex
president & CEO Jeff O'Donnell.

http://www.photomedex.com/

First we go to the pinch site and look at this patent, 6,927,205

And they moved the gov site making it a slight bit more of a problem.

Ok have it,

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=/netahtml/srchnum.htm&r=1&f=G&l=50&s1=6,927,205.WKU.&OS=PN/6,927,205&RS=PN/6,927,205

And now I don't have time to give this thing my full attention.

J go ahead and browse it if you have the time. PLease.

There are around 52 hits in pubmed for [ P + copper ]

Only a few for L-alanyl-L-histidyl-L-lysine

Leave this part off the search,
copper(II).

Only if I had the time. sigh

I must make more of it. Yeah, get the time machine. lol

****************************************

Inflammation is on my mind and really good studies are in the PiPe.

Here's a couPle of links to whats haPPPening.

Endotoxins (LPS) and how it interacts with our MHC genes may be the
last
chunk of the puzzle.

And this is the worse chinese puzzle you can imagine replete with
counterintuitive-isms to boot.

http://www.news-medical.net/?id=12874
A multi-institutional research collaborative has begun to decipher the
complex interplay of genes that underlies the body's response to major
injuries.

In a report to appear in the journal Nature, researchers from the
Inflammation and Host Response to Injury program describe their
investigation into how the process of systemic inflammation - an immune
response which affects the entire body - alters the expression of genes
within white blood cells. The findings are a first step towards the
overall goal of understanding why some individuals recover well from
traumatic injuries while others can have dangerous inflammatory
complications that may develop long after the original injury.

"Some of the most serious problems facing patients with major burns or
trauma result from out-of-control inflammation, a process we still do
not understand well," says Ronald Tompkins, MD, Sc.D., chief of the
Burns Service at Massachusetts General Hospital (MGH) and national
leader of the project. "By looking at how people respond to injury on a
genomic and proteomic level, we hope someday to be able to tailor
treatments to patients' individual needs and keep the inflammatory
response from doing more harm than good."

The project is supported by the National Institute of General Medical
Sciences (NIGMS) through what are called "glue grants," so named
because they bring together researchers from different institutions and
across several fields - for example trauma medicine, genomics,
bioinformatics and computers - to address complex scientific problems.
The inflammation team incorporates scientists from 22 research centers
who have been working together for four years.

The Nature paper, which is receiving early online release, describes
one of the group's initial experiments, led by researchers from the
Robert Wood Johnson Medical School at the University of Medicine and
Dentistry of New Jersey and the Stanford Genome Technology Center. To
examine the physiologic mechanism behind systemic inflammation, healthy
volunteers were injected with bacterial endotoxin, which produces a
widespread but controlled inflammatory response that subsides quickly.
Blood samples were taken at several points after participants received
endotoxin, and the expression levels of genes in circulating white
blood cells were analyzed and compared with those of control
participants using technologies that tested almost 45,000 probes,
representing more than 30,000 possible human genes.

The researchers found that expression levels of more than 3,700 genes
in white blood cells changed significantly during the hours after
endotoxin administration, while gene expression in control participants
was unchanged. More than half the identified genes were expressed at
lower levels, including several genes involved in the function of
mitochondria - subcellular structures that produce the cells' energy -
suggesting reduced activity of these key immune cells.

Since each gene can interact with many others in complex patterns, the
researchers turned to a database of information on thousands of human,
mouse and rats genes, compiled from more than 200,000 scientific
articles with technology developed by Ingenuity Systems Inc. Using that
tool they were able to construct inflammation-associated molecular
networks involving interactions between more than 8,000 genes. Hundreds
of these genes and pathways were not previously known to be associated
with the inflammatory process.

"Not only has this work identified novel pathways of inflammation, it
also demonstrates an approach to getting more meaning out of the data
provided by microarray gene expression profiles. We're hoping to
determine what tools are going to be most effective in producing real
knowledge from these lists of perturbed genes," says Tompkins, who is
the John Francis Burke Professor of Surgery at Harvard Medical School.

"This work represents a major step in understanding inflammation in
severely injured or burned patients. We hope this knowledge eventually
will help physicians better predict patient outcomes and tailor
treatments accordingly," said Jeremy M. Berg, PhD, director of the
NIGMS, one of the National Institutes of Health.

The senior authors of the Nature paper are Stephen Lowry, MD, chair of
Surgery at Robert Wood Johnson Medical School (RWJMS), and Ronald
Davis, PhD, professor of Biochemistry and Genetics and director of the
Stanford Genome Technology Center (SGTC). The lead authors are Steve
Calvano, PhD, RWJMS, and Wenzhong Xiao, PhD, SGTC; co-authors are
Daniel Richards, Ramon Felciano, PhD, Raymond Cho, and Richard Chen of
Ingenuity Systems Inc.; Henry Baker, PhD, Kevin Tschoeke, MD, and Lyle
Moldawer, PhD, University of Florida; Bernard Brownstein, PhD, and
Perren Cobb, MD, Washington University School of Medicine; Carol
Miller-Graziano, PhD, University of Rochester School of Medicine; and
Michael Mindrinos, PhD, SGTC.

http://www.mgh.harvard.edu/

How many genes do what and when with bacterial infections?

How about 15% of them?

http://www.news-medical.net/?id=12856

Lets recap the first article with a little more understandable one,

http://www.emaxhealth.com/39/3056.html

Randall... we may land on the P moon in another 10 years!

Fizziwig2

unread,

Sep 1, 2005, 3:32:00 PM9/1/05

"randall" <ranh...@aol.com> wrote in message

news:1125590432.2...@g44g2000cwa.googlegroups.com...

Randall, thought you might like to see the following - it might cheer you
up!

Rheumatic bracelet for 'horny' rhino

A rhinoceros which suffers from rheumatism has been fitted with a copper
necklace and bracelet to ease its pain.
snip........
......................
Thelma's keeper says the treatment appears to be working, as she is now
walking more easily........
snip

Mr Harris said: "The collective name for a group of rhinos is a clash, which
is particularly appropriate, especially for their love lives.
"Passion between two huge rhinos can be very robust and from time to time
they receive injuries.

"I must say she looks quite sweet in all her new finery, I think I might buy
her some earrings for her birthday."

............................

Whole article at the BBC site...

http://news.bbc.co.uk/1/hi/uk/810288.stm
Not a placebo then!?

Copper and Alzheimer's (also on BBC news site) have been linked so it is not
something to be used lightly.

Skeats

randall

unread,

Sep 2, 2005, 10:06:26 AM9/2/05

And or give me a spot to toot my HORN.

> Rheumatic bracelet for 'horny' rhino
>
> A rhinoceros which suffers from rheumatism has been fitted with a copper
> necklace and bracelet to ease its pain.
> snip........
> ......................
> Thelma's keeper says the treatment appears to be working, as she is now
> walking more easily........
> snip

Or she's taking pride in showing off her ORNaments.

>
> Mr Harris said: "The collective name for a group of rhinos is a clash,

Gash! This gal needs some resPite from the bulls.

Or maybe a coPPer IUD,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2372033

With the IUD she'll get the same benefits and can lay low.

Those testosterone fueled mates will loose interest and
thelma will be hoofing to a new tune.

> which
> is particularly appropriate, especially for their love lives.
> "Passion between two huge rhinos can be very robust and from time to time
> they receive injuries.
>
> "I must say she looks quite sweet in all her new finery, I think I might buy
> her some earrings for her birthday."
>

Zoo's all over the world will be decking out their inmates shortly
no doubt.

Instead of us wearing them, they'll be wearing us?

Bling bling for ding ding the chimP.

Maybe their DNA will give us a P clue or two?

http://www.mydna.com/genes/genetics/news/resources/news/200509/news_20050901_chimgene.html

> ............................
>
> Whole article at the BBC site...
>
> http://news.bbc.co.uk/1/hi/uk/810288.stm
> Not a placebo then!?
>

Run the double blind studies and let me know.

Watch out for researcher bias and errors.

http://www.newscientist.com/article.ns?id=dn7915

Most published scientific research papers are wrong, according to a new
analysis. Assuming that the new paper is itself correct, problems with
experimental and statistical methods mean that there is less than a 50%
chance that the results of any randomly chosen scientific paper are
true.

John Ioannidis, an epidemiologist at the University of Ioannina School
of Medicine in Greece, says that small sample sizes, poor study design,
researcher bias, and selective reporting and other problems combine to
make most research findings false. But even large, well-designed
studies are not always right, meaning that scientists and the public
have to be wary of reported findings.

"We should accept that most research findings will be refuted. Some
will be replicated and validated. The replication process is more
important than the first discovery," Ioannidis says.

In the paper, Ioannidis does not show that any particular findings are
false. Instead, he shows statistically how the many obstacles to
getting research findings right combine to make most published research
wrong.
Massaged conclusions

Traditionally a study is said to be "statistically significant" if the
odds are only 1 in 20 that the result could be pure chance. But in a
complicated field where there are many potential hypotheses to sift
through - such as whether a particular gene influences a particular
disease - it is easy to reach false conclusions using this standard. If
you test 20 false hypotheses, one of them is likely to show up as true,
on average.

Odds get even worse for studies that are too small, studies that find
small effects (for example, a drug that works for only 10% of
patients), or studies where the protocol and endpoints are poorly
defined, allowing researchers to massage their conclusions after the
fact.

Surprisingly, Ioannidis says another predictor of false findings is if
a field is "hot", with many teams feeling pressure to beat the others
to statistically significant findings.

But Solomon Snyder, senior editor at the Proceedings of the National
Academy of Sciences, and a neuroscientist at Johns Hopkins Medical
School in Baltimore, US, says most working scientists understand the
limitations of published research.

"When I read the literature, I'm not reading it to find proof like a
textbook. I'm reading to get ideas. So even if something is wrong with
the paper, if they have the kernel of a novel idea, that's something to
think about," he says.

> Copper and Alzheimer's (also on BBC news site) have been linked so it is not
> something to be used lightly.
>

I'll keeP it in mind.

randall... the P zoo keePer changing sPots and cages

> Skeats

randall

unread,

Sep 8, 2005, 10:50:34 PM9/8/05

Hi,

Well. I had a good time while it lasted. <sigh>

Back to the humdrum side of P.

The news.

http://www.genengnews.com/news/bnitem.aspx?name=1050878XSL_NEWSML_TO_NEWSML_WEB.xml
Biogen Idec Announces Strategic Initiative to Drive Long-Term Growth
and Accelerate Business Development Activities; Plan Expected to
Deliver Annualized Savings of $200 million to $300 million; Includes
Workforce Reduction of 17%
(...)
-- The launch of PANACLAR(TM), known as BG-12, for psoriasis patients
in Germany.

-- Divestment of assets - The company will seek to divest several
non-core assets, including the NICO clinical manufacturing facility in
San Diego, CA, property in Oceanside, CA, as well as its AMEVIVE(R)
(alefacept) product, which had revenues of $43 million in 2004. As they
occur, Biogen Idec will provide gain and loss financial information on
these divestures.

(I guess amevive was a floP. I wonder how Panaclar works? Time will
tell.)

***********

Psorcure... The Dr. S Dhawan plan,
http://www.emediawire.com/releases/2005/9/emw282279.htm

Dr. Dhawan has come across the group a few times,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=dhawan&qt_g=1&searchnow=Search+this+group

**************

UCSD study of Nuclear receptors may change anti-inflammatory
treatments,
http://www.eurekalert.org/pub_releases/2005-09/uoc--uso090705.php

(...)

In a paper being published in the September 9 issue of the journal
Cell, Christopher Glass, M.D., Ph.D., professor of cellular and
molecular medicine at the UCSD School of Medicine, and his colleagues
show that three nuclear receptor proteins - glucocorticoid, PPAR
gamma and LXR - can work together to repress the cellular responses
to certain kinds of pro-inflammatory molecular signaling. These nuclear
receptors are important in "turning off" inflammatory responses to
bacteria or viruses and allowing the cells to return to a normal state.

"Basically, we are looking at a 'tuning system' to maintain a proper
level of immunity, but without an inappropriate inflammatory response
that would contribute to a chronic disease state," Glass said.

The researchers have also, for the first time, identified on a
genome-wide level how these proteins work to influence the body's
inflammatory response. By identifying the molecular mechanism by which
each receptor inhibits particular genes involved in anti-viral
responses, more powerful drugs could be developed to fight immune
diseases such as arteriosclerosis and arthritis, with fewer side
effects.

"We now have a molecular understanding of why inflammatory responses
caused by certain infections are sensitive to glucocorticoid drugs for
example, while others are resistant," said Glass. "These observations
further explain how drugs used to inhibit one type of inflammation
could basically cripple the immune system to respond to specific viral
infections and make that disease much worse."

Glass's studies of nuclear receptors have focused on their regulation
of gene expression in the macrophage, a basic cell that recognizes
structures or patterns on pathogens that aren't present in normal
cells. The macrophage is responsible for producing and responding to
hormone-like molecules that control inflammation - important for the
understanding of immune diseases such as arteriosclerosis, psoriasis
and rheumatoid arthritis that are triggered by autoimmune responses.
While macrophages and other immune cells are essential against
infectious organisms, they can also promote chronic inflammatory
diseases.

When the macrophage thinks it sees an infection, it "turns on" or
expresses hundreds of genes, enabling the macrophage to communicate
with other cells and combat infection. In some diseases, however,
certain protein complexes become modified and begin to look like the
proteins associated with bacteria or viruses. The macrophage
misinterprets this pattern on a modified protein, which causes it to
initiate an inflammatory response. In this work, the UCSD team looked
at a number of pathogen-associated molecule patterns used to stimulate
the macrophage, with the long-term goal of finding a way to manage
inflammation without compromising the immune system.

While it had been shown in past studies that the macrophage responded
to certain drugs, it was never studied on a genomic-wide level how
receptors actually did the job of inhibiting the macrophage's
inflammatory responses. The patterns reported in the paper suggest that
each of the receptors plays a slightly different role in how the
macrophage mounts an inflammatory response, working in different but
overlapping ways.

The findings also have potential clinical significance in showing how
two or three nuclear receptors activated at the same time very
dramatically shut down inflammatory responses. This suggests that the
drug that works with one particular receptor, but with negative side
effects, could be given at a lower dose along with different drugs
targeting the other receptors. For example, one class of potent
corticoid drugs used to treat severe asthma has many negative side
effects, including high blood pressure, diabetes and obesity.

"What is of particular interest in this study," said Glass, "is that
adding two drugs together could have a much more substantial
interaction while using much less of each drug. This could result in
much better therapeutic results with fewer side effects. The
observation that these proteins can function together opens up new
avenues of clinical investigation into the treatment of diseases."

********

http://releases.usnewswire.com/GetRelease.asp?id=52665

KENSINGTON, Md., Sept. 6 /U.S. Newswire/ -- "Psoriasis Cure Now," a
nonprofit patient advocacy group, today urged the Food and Drug
Administration's Arthritis Drugs Advisory Committee to approve
abatacept for use by rheumatoid arthritis (RA) patients.

The biologic drug would be marketed by Bristol-Myers Squibb (BMS) under
the brand name Orencia.

"As we have seen repeatedly in the past, many of the same medications
that help RA patients also bring relief to people with psoriasis or
psoriatic arthritis, and vice versa," said Michael Paranzino, president
of Psoriasis Cure Now. "We would like abatacept available not just to
help RA patients, but because it may provide the psoriasis community
with an additional treatment option."
<sniP>

********

Natural herbal creamy stuff,

http://www.pressbox.co.uk/detailed/Health/Eczema_Psoriasis_Dry_Skin_-_New_100_New_Treatment_35613.html

(...)
"I have suffered from sensitive skin all my life, and developed
Psoriasis at the age of 30. I am now 44 years old and had found nothing
that soothes my dry, itchy Psoriasis" until now!

I was given a jar of your balm by a friend for my birthday and it's
been wonderful! It smells glorious, much nicer than all the medical
creams from the doctor? it smells of everything good that grows in the
earth.

?after using your Super Soothing Repair Balm, I don?t even know I?ve
got a skin complaint. I also use it to revitalise my tired, dry feet
and it does wonders. Also, a little of your balm goes a long way.

Keep up the good work? and thanks.?
Margaret, Wiltshire

Key ingredients:

Highly Nourishing & Deeply Moisturising Unrefined Shea Butter, Coconut,
Moringa & Jojoba Oil

Intensely Healing Aloe Vera, Plantain & Lavender

Supremely Soothing Calendula, Chickweed and Chamomile

Super Balancing & Strengthening Rosehip, Sea Buckthorn & Evening
Primrose Oil

Exquisitely Restorative Neem, Propolis, & Seaweed Extracts

^^^^^^^^^^^^^^^

Combating Skin Conditions with Phototherapy Treatment

http://www.medicalnewstoday.com/medicalnews.php?newsid=30102

***********

This next one is a reply to me by one of the scientist in a trial. I
asked
what a certain thing was as we have this 12(R)-hete stereo thing in
psoriasis.

(...)
Dear Randall,

thanks for your interest in our work. V631 symbolized the amino acid
631 which is valine in the murine 12R-LOX. When we mutated this amino
acid to small alanine or glycine we altered the positional specificity
of the enzyme. Whether or not such alterations may be relevant for the
pathogenesis of psoriasis I do not know. However, it is a good idea and
I will keep this in mind for our future studies on this enzyme.

Regards

Hartmut

Am Samstag, 03.09.05 um 01:31 Uhr schrieb

>
>
> Dear Hartmut,
>
> Saw your JBC abstract,
> http://www.jbc.org/cgi/content/abstract/M508260200v1
>
> Sequence determinants for reaction specificity of the murine 12 > (R)-lipoxygenase. Targeted substrate modification and site directed > mutagenesis.
>
> Meruvu S, Walther M, Ivanov I, Hammarstrom S, Furstenberger G, Krieg > P, Reddanna P, Kuhn H.
>
> Institute of Biochemistry, Charite, University Medicine Berlin, Berlin > 10117.
>
> Mammalian lipoxygenases are categorized with respect to their
> positional specificity of arachidonic acid oxygenation. Site directed
> mutagenesis identified sequence determinants for the positional
> specificity of these enzymes and recently a critical amino acid for
> the stereoselectivity was discovered. To search for sequence
> determinants of the murine 12(R)-lipoxygenase we carried out multiple
> amino acid sequence alignments and found that Phe390, Gly441, Ala455
> and Val631 align with previously identified positional determinants of
> S-lipoxygenase isoforms. Multiple site-directed mutagenesis studies on
> Phe390 and Ala455 did not induce specific alterations in the reaction
> specificity but yielded enzyme species with reduced specific
> activities and stereo-random product patterns. Gly441Ala exchange,
> which caused drastic alterations in the reaction specificity of other
> lipoxygenase isoforms, failed to induce major alterations in the
> positional specificity of the mouse 12(R)-lipoxygenase but markedly
> modified the enantioselectivity of the enzyme. When Val631, which
> aligned with the positional determinant Ile593 of the rabbit
> 15-lipoxygenase, was mutated to less space-filling residues (Ala or
> Gly) we obtained enzyme species with augmented catalytic activity and
> specifically altered reaction characteristics [major formation of
> chiral 11(R)-HETE methyl ester]. The importance of V631 for the
> stereocontrol of the murine 12(R)-lipoxygenase was confirmed with
> other substrates, such methyl linoleate and 20-HETE methyl ester.
> These data identified V631 as major sequence determinant for the
> specificity of the murine 12(R)-lipoxygenase. Furthermore, we conclude
> that substrate fatty acids may adopt different catalytically
> productive arrangements at the active site of the murine
> 12(R)-lipoxygenase and each of these arrangements may lead to the
> formation of chiral oxygenation products.
>
> PMID: 16129665

***********

Photosensitive drugs
http://www.gmtoday.com/news/health/topstory06.asp
Q: The prescription bottle containing my fluid pills
(hydrochlorothiazide) has a sticker attached that says to avoid
prolonged sun exposure. Can you tell me why?

A: The diuretic you take is one of numerous drugs reported to cause
photosensitivity reactions (sensitivity to UVA rays of the sun or
tanning devices). The result can be a skin rash, sunburn or other
adverse effect you ordinarily would not experience.

Some implicated drugs are more likely to cause reactions than others.

Your best defense is to wear protective clothing and apply a sunscreen
(at least SPF 15) when you spend time outdoors.
Here?s an updated ??keeper?? list of potentially photosensitizing drugs
alphabetized by generic name with the brand name in parentheses
<sniP>

***************

Are your nails the Pits?

You can learn a lot from a dis-eased nail,
http://www.advanceddermatologypc.com/press_nails.htm

Nail tiPs,
http://www.tipsofallsorts.com/nail.html

http://www.healthyhealing.com/interaction.html
Herb-Nutrient-Drug Interactions
Facts You Need to Know

Some P sPam received today,

http://www.apptecpharmacheminc.com/products-antipsoriasis.htm

(...)

Apptec PharmaChem Inc. (APCI) and its group of Companies have spent ~ 3
years to screen and identify a herbal formula that has been in clinical
use for many centuries to treat psoriais. In addition, the APCI team
sponsored controlled clinical stduies to scientifically evaluate and
validate the Regsor herbal formula for safety and efficacy as compared
to an allopathy control. The treatment period was 8 weeks and the study
size was 60 patients.

Safety was evaluated by recording Vital Signs, Haemogram Measurements,
Liver Function Tests, and Renal Function tests at the beginning and end
of the study. Bio-statistical analysis of the safety data revealed NO
SAFETY ISSUES were observed for either the Herbal formula or the
allopathy control.

Efficacy was evaluated by recording Erythema (Photos), Scaling
(Photos), Occurrence of New Lesions and Histopathology (Photos).
Histopathology evaluations included Parakeratosis, Stratum Granulosum,
Spongiform Pustule, Munro?s Microabscess, Acanthosis, and Dermal
Vessels Tortuosity. Bio-statistical analysis of the efficacy data
revealed that the REGSOR HERBAL FORMULA WAS SUPERIOR to the allopathy
control in management of the Psoriasis disease.

Regsor Herbal formula is available in an Ointment, Liquid Soap, Shampoo
and Oil dosage forms. For more details on the clinical study, products,
pricing and ordering please visit our website www.regsor.com

NOTE: To significantly delay the recurrence of the disease, the APCI's
R&D team has developed a soft gel capsule dosage form of the same
herbal formula for internal consumption. A controlled clinical study is
in progress to detrmine the dosage and the frequency of administartion
of the soft gel capsules.

****************

Abstract time,

Low dose MTX for crohn's,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16145336

Crohn's and ulcerative colitis (UC) folks with P,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16143122
(...)
Both UC and Crohn's disease patients had a significantly greater
likelihood of having arthritis, asthma, bronchitis, psoriasis, and
pericarditis than population controls. An increased risk for chronic
renal disease and multiple sclerosis was noted in UC but not Crohn's
disease patients. The most common nonintestinal comorbidities
identified were arthritis and asthma. Conclusions: The finding of
asthma as the most common comorbidity increased in Crohn's disease
patients compared with the general population is novel. These may be
diseases with common causes or complications of one disease that lead
to the presentation with another. Studies such as this should encourage
further research into the common triggers in the organ systems that
lead to autoimmune diseases.

PMID: 16143122

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16141522
Inhibition of the Nuclear Factor-kappaB Signaling Pathway by
Leflunomide or Triptolide also Inhibits the Anthralin-Induced
Inflammatory Response but Does Not Affect Keratinocyte Growth
Inhibition.

Feng H, Li XY, Zheng JR, Gao JW, Xu LF, Tang MY.

Department of Materia Medica, Institute of Dermatology, Chinese Academy
of Medical Sciences & Peking Union Medical College.

We performed this study to determine the relationship between
activation of nuclear factor (NF)-kappaB and inhibition of keratinocyte
growth by anthralin, which not only might be useful for a better
understanding of the role of NF-kappaB in the pathogenesis of
psoriasis, but also indicate whether the inflammatory reaction induced
by anthralin is inseparable from its antipsoriatic activity. The
involvement of NF-kappaB was assessed using the antipsoriatic drugs
leflunomide and triptolide (T(0)) as effectors, since they can inhibit
NF-kappaB activation induced by anthralin. The results showed that the
inhibition of keratinocyte growth by anthralin was not related to the
activation of NF-kappaB. Using sodium salicylate, a known NF-kappaB
inhibitor, further confirmed this conclusion. Thus it might be possible
to inhibit the inflammatory response induced by anthralin via
repression of NF-kappaB activation. We found that leflunomide or T(0)
could significantly inhibit the mRNA overexpression of interleukin-8
and intercellular adhesion molecule-1 in keratinocytes induced by
anthralin. Taken together, our data indicate that the growth inhibition
of anthralin is related to the NF-kappaB-independent signaling pathway,
and that leflunomide or T(0) could control proinflammatory cytokine
expression induced by anthralin via inhibiting the activation of
NF-kappaB.

PMID: 16141522

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16141313
Stereo-specific Induction of NF-{kappa}B Activation by Isochamaejasmin.

Tian Q, Li J, Xie X, Sun M, Sang H, Zhou C, An T, Hu L, Ye RD, Wang MW.

The Graduate School of CAS.

The root of Stellera chamaejasme L. is a traditional Chinese herb
termed Rui Xiang Lang Du and has been used to treat solid tumors,
tuberculosis and psoriasis. Exactly how Stellera chamaejasme L.
regulates cellular responses remains unclear. We examined four
biflavonoids isolated from Stellera chamaejasme L., including
isochamaejasmin, two of its stereo-isomers and a methyl derivative, in
functional assays originally designed to screen ligands for the G
protein-coupled formyl peptide receptor-like 1 (FPRL1). Isochamaejasmin
was found to induce the expression of a NF-kappaB-directed reporter
gene in transfected HeLa cells with an EC50 of 3.23 mM, independently
of FPRL1. The isochamaejasmin-stimulated NF-kappaB reporter activity
was accompanied by nuclear translocation of NF-kappaB proteins and was
blocked by a dominant negative construct of IkappaBalpha.
Isochamaejasmin also induced time-dependent phosphorylation of the
mitogen-activated protein kinases ERK1/2 and p38, and a novel protein
kinase C, PKCdelta. Likewise, inhibition of these kinases with the
respective pharmacological inhibitors significantly reduced the
isochamaejasmin-stimulated NF-kappaB activation. Interestingly, the two
stereo-isomers and the methyl derivative did not induce detectable
activation of NF-kappaB and were more cytotoxic than isochamaejasmin,
which could partially rescue cycloheximide-induced apoptosis.
Inhibition of NF-kappaB activation reversed the anti-apoptotic effect
of isochamaejasmin. These results provide the first evidence for a
potential mechanism of action by Stellera chamaejasme L., and indicate
that structurally similar compounds derived from Stellera chamaejasme
L. may have different pharmacological properties.

PMID: 16141313

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16141233
RNA Polymerase II subunit 3 is retained in the cytoplasm by its
interaction with HCR, the psoriasis vulgaris candidate gene product.

Corbi N, Bruno T, De Angelis R, Di Padova M, Libri V, Di Certo MG,
Spinardi L, Floridi A, Fanciulli M, Passananti C.

Here, we show that the subcellular localization of alpha-like RNA
polymerase II core subunit 3 (RPB3) is regulated during muscle
differentiation. We have recently demonstrated that the expression of
RPB3 is regulated during muscle differentiation and that, inside RNA
polymerase II (RNAP II), it is directly involved in contacting
regulatory proteins such as the myogenic transcription factor Myogenin
and activating transcription factor ATF4. We show for the first time,
that RPB3, in addition to its presence and role inside the RNAP II core
enzyme, accumulates in the cytoplasm of cycling myogenic cells and
migrates to the nucleus upon induction of the differentiation program.
Furthermore, using human RPB3 as bait in a yeast two-hybrid system, we
have isolated a novel RPB3 cytoplasmic interacting protein, HCR. HCR,
previously identified as alpha-helix coiled-coil rod homologue, is one
of the psoriasis vulgaris (PV) candidate genes. In cycling myogenic
C2C7 cells, we show that the RPB3 protein directly interacts with HCR
within the cytoplasm. Finally, knocking down HCR expression by RNA
interference, we demonstrate that HCR acts as cytoplasmic docking site
for RPB3.

PMID: 16141233

A gene that may directly influence psoriasis,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16140218
Roxithromycin suppresses involucrin expression by modulation of
activator protein-1 and nuclear factor-kappaB activities of
keratinocytes.

Takahashi H, Hashimoto Y, Ishida-Yamamoto A, Iizuka H.

Department of Dermatology, Asahikawa Medical College, 2-1-1-1
Midorigaokahigashi, Asahikawa 078-8510, Japan.

BACKGROUND:: Roxithromycin (RXM), a new 14-member macrolide antibiotic,
is effective for chronic airway diseases such as diffuse
panbronchiolitis and bronchial asthma. Recent study disclosed that RXM
inhibits nuclear factor-kappaB (NF-kappaB)-mediated inflammation.
Involucrin is one of the precursor proteins of the cornified cell
envelope (CE) and is markedly increased in inflammatory skin diseases
such as psoriasis. However, its molecular mechanism of action remains
unknown. OBJECTIVE:: To determine the effect of RXM on involucrin
expression of keratinocytes. METHODS:: We constructed chloramphenicol
acetyltransferase (CAT)-involucrin promoter expression vector and CAT
assay was performed. Furthermore, western blot and RT-PCR were
performed to examine the expression of involucrin in RXM-treated
cultured human keratinocytes. RESULTS:: The increased involucrin
expression by 12-O-tetradecanoylphorbol acetate (TPA) was suppressed by
10(-6)M RXM and the maximal inhibitory effect was observed at 48h. RXM
suppressed increased CAT activity by TPA and the effect was not
inhibited by H-7 or cafferic acid phenethyl ester (CAPE). Deletion of
T1 region (-119 to -113) of involucrin promoter completely abolished
TPA-dependent stimulatory and RXM-dependent inhibitory promoter
activity. Gel shift assay showed that c-Jun (but not p65) selectively
binds to the T1 region. The assay of activator protein-1 (AP-1) and
NF-kappaB activities revealed that RXM decreased both transcriptional
activities. Co-transfection of c-jun and c-fos expression vectors, or
p65 and p50 expression vectors, rescued decreased CAT activity by RXM,
respectively. CONCLUSION:: Our study demonstrated for the first time
that involucrin expression of keratinocytes is suppressed by RXM
through direct inhibition of AP-1 and indirect inhibition of NF-kappaB.

PMID: 16140218

randall

unread,

Sep 9, 2005, 12:51:38 PM9/9/05

randall wrote:
> Hi,
>
> Well. I had a good time while it lasted. <sigh>
>
> Back to the humdrum side of P.
>
> The news.
>
>
> http://www.genengnews.com/news/bnitem.aspx?name=1050878XSL_NEWSML_TO_NEWSML_WEB.xml
> Biogen Idec Announces Strategic Initiative to Drive Long-Term Growth
> and Accelerate Business Development Activities; Plan Expected to
> Deliver Annualized Savings of $200 million to $300 million; Includes
> Workforce Reduction of 17%
> (...)
> -- The launch of PANACLAR(TM), known as BG-12, for psoriasis patients
> in Germany.
>
> -- Divestment of assets - The company will seek to divest several
> non-core assets, including the NICO clinical manufacturing facility in
> San Diego, CA, property in Oceanside, CA, as well as its AMEVIVE(R)
> (alefacept) product, which had revenues of $43 million in 2004. As they
> occur, Biogen Idec will provide gain and loss financial information on
> these divestures.
>
> (I guess amevive was a floP. I wonder how Panaclar works? Time will
> tell.)
>
>

<sniP.

Do you want to know what really big news is? Biogen laying off 17% of
their workers and selling off amevive?
http://news.google.com/news?auth=DQAAAGgAAABCE5CcPkVt9K9YR7W9Vd28G_SXzyP4c1SH2h7RjVpDCMUmsTzORruDKWo49cRwswR7mEwd_a_rwr6UCrw4r2JtgIYn9fcH7KDI3fGW4pg5FVaM2ZCVQTfrJJEh3TlPpHJ744qDKX1mllKkb51f4QeB&tab=gn&ie=UTF-8&scoring=d&q=psoriasis+biogen+17&btnG=Search+News

Or could it be a switch in tactics?

Panaclar anyone?
http://www.google.com/search?q=panaclar&svnum=10&hl=en&lr=&sa=N&tab=iw

Are you thinking what i'm thinking JX?

Lets run the image google on biogen,
http://images.google.com/images?auth=DQAAAGgAAABCE5CcPkVt9K9YR7W9Vd28G_SXzyP4c1SH2h7RjVpDCMUmsTzORruDKWo49cRwswR7mEwd_a_rwr6UCrw4r2JtgIYn9fcH7KDI3fGW4pg5FVaM2ZCVQTfrJJEh3TlPpHJ744qDKX1mllKkb51f4QeB&tab=ni&ie=UTF-8&scoring=d&q=psoriasis+biogen&sa=N

And check out the first hit,
http://www.shef.ac.uk/~biogen/Research/research_skin.html

Does it look like these guys are giving uP?

NoPe. But they are changing directions for whatever reasons.

Could low tech inflammatory modulators be on the horizon?

I'm not going to hang on the panaclar theme. I'll let your responses
be the guide for that venue. (But IMHO the headlines should be:: Biogen
has low tech FAE on the radar. Sells off the expensive high tech non
sense
plants--- Bioglogicals going down the drain? )

While FAE is fairly low tech. I'm going lower.

Lets check pubmed for one mentioned in this group many times.
First look at it,
http://biology.missouristate.edu/Herbarium/Plants%20of%20the%20Interior%20Highlands/Flowers/Mahonia%20aquifolium%20-%201.jpg

Aka- oregon grape,
http://www.laspilitas.com/plants/420.htm

On pubmed,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16148424

A Report on Three Recent Clinical Trials Using Mahonia aquifolium 10%
Topical Cream and a Review of the Worldwide Clinical Experience With
Mahonia aquifolium for the Treatment of Plaque Psoriasis.

Gulliver WP, Donsky HJ.

1Memorial University and Newlab Clinical Research Inc., St John's,
Newfoundland, Canada; and 2Director, Dermatology and Cosmetic Center
and University of Rochester Medical School, Rochester, NY, USA.

This monograph summarizes 3 recent clinical trials and the worldwide
clinical experience with Mahonia aquifolium in patients with psoriasis.
Study 1 was an open-label study to evaluate the safety of Mahonia
aquifolium in 39 patients treated for 12 weeks. Assessments made were
modified PASI, global assessment, psoriasis history questionnaire,
Dermatology Life Quality Index, and Psoriasis Disability Index. The
results indicate statistically significant improvement in PASI score
and Dermatology Life Quality Index after 4 weeks of treatment. This
response continued 1 month after the end of treatment. Study 2 was a
clinical trial of 32 patients with mild to moderate bilateral psoriasis
treated up to 6 months. One side of the body received Mahonia and the
other standard psoriatic treatment (eg, Dovonex cream). The primary
outcomes were patient ratings of the Mahonia-treated side alone and the
comparison between treatments received on each side of their body.
Eighty-four percent of patients rated the Mahonia-treated psoriasis as
good to excellent response. When compared with standard treatment, 63%
of patients rated Mahonia aquifolium equal to or better than the
standard psoriatic treatment. Study 3 was an observational study of 33
patients with mild to moderate bilateral psoriasis treated for 1 month.
The results indicate improvement in psoriasis after 1 week of
treatment. The side treated with Mahonia did as well or better than the
side treated with the vehicle cream. Results from these 3 open-label
clinical trials are in agreement with published data that include
placebo-controlled studies. Taken together, these clinical studies
conducted by several investigators in several countries indicate that
Mahonia aquifolium is a safe and effective treatment of patients with
mild to moderate psoriasis.

PMID: 16148424

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15476315
Antimicrobial activity of Mahonia aquifolium crude extract and its
major isolated alkaloids.

Slobodnikova L, Kost'alova D, Labudova D, Kotulova D, Kettmann V.

Institute of Microbiology of the Medical Faculty and the Faculty
Hospital, Comenius University, Odbojarov 10, SK-83232 Bratislava,
Slovakia.

The crude extract of Mahonia aquifolium (Pursh) Nutt. stem bark and its
two main protoberberine alkaloids, berberine and jatrorrhizine, were
tested for their in vitro antimicrobial activity. Twenty strains of
coagulase-negative staphylococci and 20 strains of Propionibacterium
acnes isolated from skin lesions of patients with a severe form of
acne, and 20 strains of Candida sp. isolated from chronic vulvovaginal
candidoses were tested for their susceptibility to crude extract and
two isolated alkaloids. The minimum inhibitory concentrations obtained
in this study illustrate the varying degrees of antibacterial and
antifungal activity of the tested agents. The results indicate a
rational basis for the traditional use of Mahonia aquifolium for
localized skin and mucosal infection therapy, as well as for the
possible development of a preparation for supportive therapy of the
diseases mentioned above.

PMID: 15476315

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10352377

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12916091

*************

Could low tech and nutrition be our ultimate salvation?

The ucsd receptor study will lead the way to working with turning
down the inflammation genes.

But untill then, common sense cheaP easy to obtain suPPlements are
heading the list.

randall... tyPing his fingers to dexterity and clearness.

randall

unread,

Sep 11, 2005, 8:01:12 PM9/11/05

Hi,

It must have been what cruiser, my suPPosed accomplice, said.

That made me reflect on what don said in a post a week or two back.

I think i answered a post with one word or link and don said he liked
it.

For some reason his reasoning stuck with me.

So,
If brevity is the soul of wit.

I must be the sole of Pwit.

Or lucky enough to find magic in God's green earth.

As some plants keeP PoPing uP,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16150204
Clinical observation on effect of triptolide tablet in treating
patients with psoriasis vulgaris.

Wu SX, Guo NR.

Institute of Dermatology, Chinese Academy of Medical Sciences, Peking
Union Medical College, Nanjing (210042). E-mail: shao...@yahoo.com.

OBJECTIVE: To investigate the effects of triptolide tablet in the
treatment of patients with psoriasis vulgaris. METHODS: By an open
clinical study of 103 patients with psoriasis vulgaris. Psoriasis area
severity index (PASI) was measured and recorded before and after
treatment for efficacy evaluation. RESULTS: Of the 103 patients,
markedly effective was got in 41 (39.7%), improved in 37 (35.8%) and
ineffective in 25 (24.5%), the total effective rate being 75.7%, and
the adverse reaction was shown only in few patients with decreased WBC
during the treatment period. CONCLUSION: Triptolide tablet is effective
for the treatment of psoriasis vulgaris during the one-year follow-up.

PMID: 16150204

Botanical source: from Triptergium wilfordii Hook F.
http://sinobest.en.ec21.com/2/Triptolide_99_.html

Calbiochem Pdf safety sheet, (very day-- pass on it)
http://www.emdbiosciences.com/msds/English/645900English.pdf

P ng check,
http://groups.google.com/groups?q=Triptolide+psoriasis&qt_s=Search

Back to pubmed,

PMID: 16141522

http://groups.google.com/groups?q=leflunomide+psoriasis&qt_s=Search

http://groups.google.com/groups?q=arava+psoriasis&qt_s=Search

All once again scoring the systemic from local toPical aPPlications.

A topical used exclusively in affected areas. Makes sense.

randall

unread,

Sep 13, 2005, 12:32:48 PM9/13/05

Hi,

Since we have a CFS exPert in our midst. He may chime in as WELL.

The main drugs in use to block TNF and clear psoriasis are the
biologicals.

Is there a viral proponent pushing those Th1 TNF,s?

A mutated alien virus?

http://www.innovations-report.com/html/reports/life_sciences/report-49043.html

LIAI scientists discover cellular switch for controlling immune system
function

Research could lead to future treatment advancements for rheumatoid
arthritis and other autoimmune diseases

A major finding by researchers at the La Jolla Institute for Allergy &
Immunology (LIAI) has identified a previously unknown cellular
mechanism that acts as an off switch for immune system function. The
discovery could lead to the future development of new treatments for
autoimmune diseases such as rheumatoid arthritis, multiple sclerosis
and Crohn's disease.

In autoimmune diseases, the immune system, which normally wards off
invading viruses and bacteria, instead mistakenly attacks normal body
tissues, leading to illness. "By understanding this cellular process
for turning off immune system activity, we are hopeful this will lead
to new treatments that will stop unwanted immune responses, such as
those which occur in autoimmune diseases," said LIAI scientist Carl
Ware, Ph.D., who co-led the study with LIAI researcher Chris Benedict,
Ph.D. The research team also involved scientists from Rush Medical
Center and Northwestern University in Chicago and Washington University
in St. Louis.

The findings will be published September 13 in the Proceedings of the
National Academy of Sciences (PNAS) in a paper entitled,
"Evolutionarily Divergent Herpesviruses Modulate T cell activation by
Targeting the Herpesvirus Entry Mediator (HVEM) Cosignaling Pathway."

Jennifer Gommerman, Ph.D., and Tania Watts, Ph.D., of the University of
Toronto's Department of Immunology, who co-wrote a PNAS commentary on
the paper scheduled for online publication this week, called the
findings a significant advancement. "This discovery underscores the
importance of this pathway in immune regulation and advances our
knowledge of how to develop effective treatments for certain
illnesses."

In the study, the team of scientists looked at two members of the
herpes family of viruses, cytomegalovirus and herpes simplex virus,
because of their ability to lay dormant in the immune system without
causing disease. "These viruses teach us how to manipulate the immune
system," Dr. Ware said. "We found that these two very different viruses
were attacking the same communication pathway in the immune system." By
disrupting that pathway, the viruses were keeping T lymphocytes - which
are white blood cells that fight disease - from communicating with
other cells in the immune system. "It's kind of like jamming a phone
system," Dr. Ware explained. "If communication gets cut off, messages
won't get through and nothing is going to get done."

Central in the viruses' ability to manipulate immune system
communication was a cellular protein called the Herpesvirus Entry
Mediator (HVEM), which the scientists found effectively worked as an
"off and on switch" for immune responses. Several cellular proteins --
members of the tumor necrosis factor (TNF) family -- interact with HVEM
to enable this immune system communication switch. HVEM is part of a
larger TNF family of molecules involved in a wide variety of important
immune system functions. The finding is the latest from Dr. Ware's
laboratory involving TNF receptors, which he has been studying for more
than 20 years. Drugs targeted at the TNF family are prominent
treatments against some autoimmune diseases, including rheumatoid
arthritis, psoriasis and Crohn's disease.

Mitchell Kronenberg, Ph.D., LIAI President and Scientific Director,
said the team's findings are regarded as very exciting by the
scientific community. "This research could one day lead to the
development of drugs that mimic the action of HVEM," he said. "That
could give medical science a new method for reducing or even stopping
the inflammation associated with rheumatoid arthritis and other
autoimmune diseases."

The findings also have implications beyond autoimmune disease,
including possible application in treatments for infectious diseases
and cancer. "An important part of our findings is that HVEM can not
only switch off immune system response but it can also switch it on,"
Dr. Ware said. "This may be valuable in fighting infectious disease,
where the body needs a stronger immune response. It also could aid in
prompting immune cells to attack cancerous cells."

In addition to Ware and Benedict, other researchers participating in
the study from the La Jolla Institute for Allergy & Immunology were
Timothy Cheung, Ian Humphreys, Karen Potter, Paula Norris, Heather
Shumway, Bonnie Tran, Ginelle Patterson, Rochelle Jean-Jacques and Miri
Yoon. In Chicago, researchers participating were Patricia Spear from
Northwestern University and Nell Lurain from Rush Medical Center, and
in St. Louis, Kenneth Murphy from Washington University. The research
was supported in part by grants from the National Institute of Allergy
and Infectious Diseases, part of the National Institutes of Health.

More information: www.liai.org

************

The pubmed for the above,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16131544
Evolutionarily divergent herpesviruses modulate T cell activation by
targeting the herpesvirus entry mediator cosignaling pathway.

Cheung TC, Humphreys IR, Potter KG, Norris PS, Shumway HM, Tran BR,
Patterson G, Jean-Jacques R, Yoon M, Spear PG, Murphy KM, Lurain NS,
Benedict CA, Ware CF.

Division of Molecular Immunology, La Jolla Institute for Allergy and
Immunology, 10355 Science Center Drive, San Diego, CA 92121.

The herpesvirus entry mediator (HVEM), a member of the TNF receptor
(TNFR) superfamily, can act as a molecular switch that modulates T cell
activation by propagating positive signals from the TNF-related ligand
LIGHT (TNFR superfamily 14), or inhibitory signals through the Ig
superfamily member B and T lymphocyte attenuator (BTLA). Competitive
binding analysis and mutagenesis reveals a unique BTLA binding site
centered on a critical lysine residue in cysteine-rich domain 1 of
HVEM. The BTLA binding site on HVEM overlaps with the binding site for
the herpes simplex virus 1 envelope glycoprotein D, but is distinct
from where LIGHT binds, yet glycoprotein D inhibits the binding of both
ligands, potentially nullifying the pathway. The binding site on HVEM
for BTLA is conserved in the orphan TNFR, UL144, present in human CMV.
UL144 binds BTLA, but not LIGHT, and inhibits T cell proliferation,
selectively mimicking the inhibitory cosignaling function of HVEM. The
demonstration that distinct herpesviruses target the HVEM-BTLA
cosignaling pathway suggests the importance of this pathway in
regulating T cell activation during host defenses.

PMID: 16131544

*********************

We have talked and i've used the creosote product, Larrea shegoi to
some help in the past,
http://groups.google.com/groups?q=herpes+psoriasis&qt_s=Search

Let,s go back to pubmed to confirm this herPes + P connection?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16106447
LIGHTing up dendritic cell activation: Immune regulation and viral
exploitation.

Pollara G, Katz DR, Chain BM.

Windeyer Institute of Medical Sciences, 46 Cleveland Street, London,
United Kingdom.

The maturation state of dendritic cells (DC) is regulated by a variety
of factors. These include ligands expressed by T cells, such as members
of the TNF superfamily. Recent studies have highlighted the role of one
such molecule, LIGHT, as a positive regulator of DC biology, promoting
the maturation of these cells through the activation of NF-kappaB
pathways. In addition, HSV-1 envelope glycoproteins can also bind the
LIGHT receptor, herpes virus entry mediator (HVEM), and activate
similar downstream signalling pathways in DC. The consequence of this
host-viral interaction may be a novel pathway of viral immune evasion.
(c) 2005 Wiley-Liss, Inc.

PMID: 16106447

If this new pathway adds light to these pathways to cure crohn's, it
may narrow the Path to P.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15944326

The critical role of LIGHT in promoting intestinal inflammation and
Crohn's disease.

Wang J, Anders RA, Wang Y, Turner JR, Abraham C, Pfeffer K, Fu YX.

Department of Pathology, University of Chicago, Chicago, IL 60637, USA.

Crohn's disease (CD) is a type of inflammatory bowel disease associated
with increased Th1 cytokines and unique pathological features. However,
its pathogenesis has not been fully understood. Previous studies showed
that homologous to lymphotoxin, exhibits inducible expression, competes
with herpesvirus glycoprotein D for HVEM on T cells (LIGHT) transgenic
(Tg) mice develop autoimmunity including intestinal inflammation with a
variable time course. In this study, we establish an experimental model
for CD by adoptive transfer of Tg mesenteric lymph node cells into
RAG(-/-) mice. The recipients of Tg lymphocytes rapidly develop a
disease strikingly similar to the key pathologic features and cytokine
characterization observed in CD. We demonstrate that, as a
costimulatory molecule, LIGHT preferentially drives Th1 responses.
LIGHT-mediated intestinal disease is dependent on both of its
identified signaling receptors, lymphotoxin beta receptor and herpes
virus entry mediator, because LIGHT Tg mesenteric lymph node cells do
not cause intestinal inflammation when transferred into the lymphotoxin
beta receptor-deficient mice, and herpes virus entry mediator on donor
T cells is required for the full development of disease. Furthermore,
we demonstrated that up-regulation of LIGHT is associated with active
CD. These data establish a new mouse model resembling CD and suggest
that up-regulation of LIGHT may be an important mediator of CD
pathogenesis.

PMID: 15944326

I sorta hoPed for a lectin P culprit. How about nectin instead?
I do find Pectin helPful for health and so should you.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16036799
Nectin-1/HveC Mediates herpes simplex virus type 1 entry into primary
human sensory neurons and fibroblasts.

Simpson SA, Manchak MD, Hager EJ, Krummenacher C, Whitbeck JC, Levin
MJ, Freed CR, Wilcox CL, Cohen GH, Eisenberg RJ, Pizer LI.

Department of Pediatrics, Section of Infectious Diseases, University of
Colorado Health Sciences Center, Denver, Colorado 80262, USA.

Immunocytochemistry detects nectin-1/HveC, nectin-2/HveB, and HVEM/HveA
on the surface of sensory neurons and fibroblasts grown as primary
cultures from human dorsal root ganglia. Viral entry into these
cultured cells was assayed by infection with a recombinant herpes
simplex virus type 1 (HSV-1) expressing green fluorescent protein.
Soluble, truncated nectin-1 polypeptide, as well as polyclonal and
monoclonal antibodies against nectin-1, inhibited infection of neurons,
whereas polypeptides and antibodies capable of inhibiting HSV-1
interaction with nectin-2 and herpesvirs entry mediator (HVEM) failed
to prevent infection of neuronal cells. These results demonstrate that
nectin-1 is the primary receptor for HSV-1 entry into human fetal
neurons. Viral entry into fibroblasts was also reduced by soluble
nectin-1 but not by soluble HVEM. However, in contrast to the results
obtained with neurons, antibodies against receptors failed to inhibit
entry into fibroblasts, indicating that unlike neurons, fibroblasts
have multiple receptors or mechanisms for HSV-1 entry.

PMID: 16036799

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15771565

How about a abstract that says herpes and P?

Here's one,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15855153
Identification and characterization of a novel, psoriasis
susceptibility-related noncoding RNA gene, PRINS.

Sonkoly E, Bata-Csorgo Z, Pivarcsi A, Polyanka H, Kenderessy-Szabo A,
Molnar G, Szentpali K, Bari L, Megyeri K, Mandi Y, Dobozy A, Kemeny L,
Szell M.

Department of Dermatology and Allergology, University of Szeged, Szeged
6720, Hungary.

To identify genetic factors contributing to psoriasis susceptibility,
gene expression profiles of uninvolved epidermis from psoriatic
patients and epidermis from healthy individuals were compared. Besides
already characterized genes, we identified a cDNA with yet unknown
functions, which we further characterized and named PRINS (Psoriasis
susceptibility-related RNA Gene Induced by Stress). In silico
structural and homology studies suggested that PRINS may function as a
noncoding RNA. PRINS harbors two Alu elements, it is transcribed by RNA
polymerase II, and it is expressed at different levels in various human
tissues. Real time reverse transcription-PCR analysis showed that PRINS
was expressed higher in the uninvolved epidermis of psoriatic patients
compared with both psoriatic lesional and healthy epidermis, suggesting
a role for PRINS in psoriasis susceptibility. PRINS is regulated by the
proliferation and differentiation state of keratinocytes. Treatment
with T-lymphokines, known to precipitate psoriatic symptoms, decreased
PRINS expression in the uninvolved psoriatic but not in healthy
epidermis. Real time reverse transcription-PCR analysis showed that
stress signals such as ultraviolet-B irradiation, viral infection
________(herpes simplex virus)__________, and translational inhibition
increased the RNA level of PRINS. Gene-specific silencing of PRINS by
RNA interference revealed that down-regulation of PRINS impairs cell
viability after serum starvation but not under normal serum conditions.
Our findings suggest that PRINS functions as a noncoding regulatory
RNA, playing a protective role in cells exposed to stress. Furthermore,
elevated PRINS expression in the epidermis may contribute to psoriasis
susceptibility.

PMID: 15855153

Can't forget the Bertok strategy,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15561510

(I'm doing a modified bertok right now. using vitamin C to increase
bile
production. Plus some IP6. which is going exlnt.)

Lithium kicks some herpes butt and a dozen other pathways,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15107743
But lithium is a P trigger. So this one is couter-intuitive. No
surPrise.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16047184

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15906276

What do you think?

Taking herpes to the woodshed or just refitting it with a bit of
dna/rna to
stop the TNF trigger?

One more possible pathway?

Ok Steve? Your virus or not?

randall... and is it all subclinical?

randall

unread,

Sep 14, 2005, 2:25:52 PM9/14/05

randall wrote:

I felt this posted yesterday worth reading again.

>http://www.innovations-report.com/html/reports/life_sciences/report-49043.html

>
> Central in the viruses' ability to manipulate immune system
> communication was a cellular protein called the Herpesvirus Entry
> Mediator (HVEM), which the scientists found effectively worked as an
> "off and on switch" for immune responses. Several cellular proteins --
> members of the tumor necrosis factor (TNF) family -- interact with HVEM
> to enable this immune system communication switch. HVEM is part of a
> larger TNF family of molecules involved in a wide variety of important
> immune system functions. The finding is the latest from Dr. Ware's
> laboratory involving TNF receptors, which he has been studying for more
> than 20 years. Drugs targeted at the TNF family are prominent
> treatments against some autoimmune diseases, including rheumatoid
> arthritis, psoriasis and Crohn's disease.
>

>
> The abstract for the above,

I don't feel like the virus is it for P. But part of a wider
puzzle if any part at all. Or maybe something pleomorphic?

Do we have HVEM driving our T cells and pumPing out TNF's?

Is there a way to start and stop the production of TNFs via
HVEM? Can it be dialed in for oPtimal health even?

I know JX is thinking that right now. Why tiP the aPPle cart?

The tnf family,
http://www.imgenex.com/TNFFamily.php

What comes uP for me in this P game is what i'm doing right now.
IP6 and high vitamin C dosages (6 grams a day-- 3 gram with each meal).

So am i having an effect on dormant herpes virus?

http://groups.google.com/groups?q=herpes+vitamin+c&qt_s=Search

Or is the dePleted iron stores from the IP6 doing the job?

Or a combo of both? Lately i've wondered about caco2 cells and
IP6 connections as genes downstream have to be affected by whatever
IP6 is doing along the Gi tract and once systemic.

As to other valid suPPlements in the current trials.

I've been taking less NAC on purpose to see if my bodies taken
over the production of SOD. And cruiser, don't bother with taking
glutathione as a stand alone. NAC is better on an order of 100X's.
The difference if there is any in your trial by taking or not NAC
is likely about the same as night and day on your results.

Ok so much for MY trials.

Moving on to real P news from around the world.

&&&&&&&&&&&

Psoriatic,

Dennis Potter of singing detective fame on DVD,
http://www.dvdtimes.co.uk/content.php?contentid=58523
One of the most influential writers of TV drama from the 60's through
to the 90's, who in addition had a hand in the making of several
feature films, Dennis Potter's total screen output is large by any
reckoning, consisting of twenty-nine single TV plays, eleven TV serials
and nine films. But up until recently there was little of his work
available on DVD, and because of the vagaries of search engines in
online shops - which work by title, actor and director, and not writer
- what was available was hard to find. That situation has changed, and
now there is a reasonable body available on DVD; and moreover the name
'Dennis Potter' has been incorporated into many of the package titles,
so search engines can find it. In this case, at least, the writer has
been elevated to his rightful position in the scheme of importance.
<sniP>

Good read on Potter but if that's not enough,
http://www.dvdtimes.co.uk/content.php?contentid=58524

Are you one of those folks who can't live without hating George Bush?
This next guy is,
http://www.dissidentvoice.org/Sept05/Drolette0914.htm

One of his theories is that George Bush may be afflicted by the
heartbreak of P (HofP).
>From the link:::
"Why, you inquire in unbelieving wonder, do these people not see Bush
for the mendacious, meat-headed, mumbly-mouthed murderer he is?

Good question. It's one that has bedeviled us for years. Theories
abound. Could it be the nonstop disinformation shoveled out by the
bought-and-paid for U.S. whoreporate media? Mass
stupidity/apathy/insanity? The disorienting heartbreak of psoriasis?
Who knows?

randall::: I know. It's not the P. P made Potter a great author
possibly. But other's would argue that as well. So, should Bush not
have P, what is this man saying? That P is an excuse
for murder? To what depths does our P angst really dive?

Bush is extremely healthy for a man his age and if he had P we'd know.

I'd say that if your heart is full of hate then look in the mirror.

If you see psoriasis all over your soul, is it just hatred?

Surely your blood boils once in a while. But P is more about being
humble isn't
it?

And would mentioning the HofP in a hit piece like this not say more
about
the author then the subject?

Is the Pot willing to look in the mirror?

Let alone have the skillet fry uP his triPe?

***************************

I've mentioned Bertok many times recently. He's of the mind that
cleaning the bowel and increasing digestion with ox and porcine bile
will clear your P.

And now a link from some company in his neck of the woods that's a
toPical.

What does that do to Bertok's theory? Not to clear huh?

>From Hungary with Love for you P'sters!

http://www.24-7pressrelease.com/view_press_release.php?rID=8262
New, natural skincare product provides long-awaited relief for many
Psoriasis sufferers.

/24-7PressRelease/ - BUDAPEST, HUNGARY, September 14, 2005 - For too
long Psoriasis sufferers have had to cope with bothersome and
embarrassing symptoms, including itchiness, irritation and desquamation
(peeling). Optoderma Cellular Memorizer has clinically proven results
without the side-effects caused by many conventional treatments. It's
simple, easy-to-use system restores the natural functions of the skin,
bringing relief to millions.

In 2004, Optoderma Cellular Memorizer was clinically tested on
long-term psoriasis sufferers in the Aeskulap Hospital in Brunnen,
Switzerland (Swiss Centre for Clinical Holistic Medicine). Additional
control tests in Germany, Holland, Hungary and Switzerland confirm its
exciting results. The vast majority of test patients experienced relief
from itching after only a few days. After a six-week period, a highly
significant 77% of test patients reported that the symptoms had either
gone, or were drastically reduced. Clinical test reports can be seen in
detail on the website at www.optoderma.com. <sniP>

Do's and don'ts page (from Canada)
http://www.optoderma.com/main.php?folderID=847
English page for products,
http://www.optoderma.com/main.php?folderID=861&seturl=default&setlang=eng

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Now to get back to a very real P pathway. Arachidonic acid and P!
http://www.mydna.com/health/asthma/news/resources/news/200509/news_20050913_cidgra.html
Grant awarded to study chronic inflammatory diseases
Tue 13 Sep 2005 07:42 am CST
FLORIDA (myDNA News)

Dr. Joshua Rokach, Florida Tech Chemistry Professor and Director of the
Claude Pepper Institute, has been awarded a four-year $1.3 million
research grant from the National Institutes of Health (NIH). The grant
from the National Heart, Lung, and Blood Institute will allow Dr.
Rokach to continue his studies on chronic inflammatory diseases.

Rokach's research will focus on the enzymatic reaction of
5-hydroxyeicosanoid dehydrogenase in certain types of white blood
cells, or leukocytes, which contributes to such diseases as asthma,
inflammatory bowel disease and psoriasis. The research will center on
the design and synthesis of radio- and photo-affinity ligand molecules
that can bind to the enzyme catalytic cavity. Such molecules, when
irradiated with ultraviolet light, become permanently bound to the
disease-causing enzyme but not to other proteins. When the enzyme is
radioactively labeled, it is possible to isolate and determine its
structure.

Rokach has received worldwide recognition for the first syntheses of
major inflammatory mediators such as leukotrienes and lipoxins, which
are responsible for allergies affecting the lungs and nose. The
availability of these synthetic mediators has opened the field to
medical research in the areas of allergy and inflammation. Among his
other accomplishments, Rokach was responsible for the development of
the drug "Singulair", a leukotriene-D4 antagonist, used by millions of
allergy sufferers for the relief of asthma and rhinitis symptoms.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15893379

Biochemistry, biology and chemistry of the 5-lipoxygenase product
5-oxo-ETE.

Powell WS, Rokach J.

Meakins-Christie Laboratories, Department of Medicine, McGill
University, 3626 St. Urbain Street, Montreal, Que., Canada H2X 2P2.
william...@mcgill.ca

5-Oxo-ETE (5-oxo-6,8,11,14-eicosatetraenoic acid) is an arachidonic
acid metabolite formed by the oxidation of
5S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) by
5-hydroxyeicosanoid dehydrogenase (5-HEDH), a microsomal enzyme found
in leukocytes and platelets. 5-HEDH is highly selective for 5S-HETE,
and displays little activity for other monohydroxy metabolites of
arachidonic acid. The synthesis of 5-oxo-ETE requires NADP(+) and can
be stimulated by activation of the respiratory burst and by oxidative
stress. 5-Oxo-ETE is a chemoattractant for eosinophils and neutrophils,
and elicits a variety of responses in these cells, including actin
polymerization, calcium mobilization, integrin expression, and
degranulation. Its primary target appears to be the eosinophil, and
among lipid mediators it is the strongest chemoattractant for these
cells. It is also a chemoattractant for monocytes and stimulates the
proliferation of prostate tumor cells. Its actions are mediated by a
G(i) protein-coupled receptor (OXE receptor) that is highly expressed
by eosinophils>neutrophils>monocytes. When administered in vivo in both
humans and rodents it elicits tissue eosinophilia, suggesting that it
may be an important mediator in allergic diseases such as asthma, and
that the development of drugs designed to prevent its formation or
effects may be useful therapeutic agents in these diseases.

PMID: 15893379

Gosh it's sure a lot of fun how these pathways go round in circles.

http://groups.google.com/groups?q=psoriasis%20arachidonic%20acid&hl=en&lr=&sa=N&tab=wg

Now we have 285 hits for AA + P.

How big a HIT is it?

randall... many genes more pathways & the Puzzle grows!

randall

unread,

Sep 15, 2005, 9:21:04 PM9/15/05

Hi,

P news from Pubmed. As the google news search engines are
taking way to long to post. Must be a virus.

Back to P.

How's your parathyroid doing? If your severe it may not be functioning
right.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16159734
Serum Levels of Parathyroid Hormone and Parathyroid-related Peptide in
Psoriasis.

Regana MS, Ezquerra GM, Millet PU.

Psoriasis and Phototherapy Center, Department of Dermatology, Hospital
Universitari Sagrat Cor, Teaching Unit of University of Barcelona,
Barcelona, Spain.

Psoriasis is a common skin disorder that may be triggered by hormonal
disturbances, among other factors. Some studies have demonstrated an
elevation of serum parathyroid hormone (PTH) levels in psoriasis and
several other diseases of keratinization of unknown aetiology.
PTH-related peptide (PTH-rp), on the other hand, is a potent inhibitor
of epidermal cell growth factor and is not expressed in psoriatic skin.
Serum levels of this peptide have not been reported in psoriasis.
Immunoassay was used to measure serum PTH and PTH-rp in 22 patients
with plaque-type psoriasis before and after treatment with mometasone
furoate. Results were compared with a group of 20 healthy,
non-psoriatic volunteers. Serum PTH levels were significantly elevated
in the psoriatic group compared with the control group (p = 0.001) and
were significantly reduced after treatment (p = 0.01). A correlation
was found between pretreatment serum PTH levels and psoriasis area and
severity scores (PASI) (r = 0.42; p = 0.01). In contrast, serum PTH-rp
levels were not different between psoriatics and controls and were not
affected by treatment. These findings indicate that serum PTH
concentrations reflect disease activity in patients with psoriasis.

PMID: 16159734

This Novasome cream seems ideal,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12932245

I wonder why this area wasn't looked into sooner?

They've known about it at least since 1992,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1350411
Acta Derm Venereol. 1992;72(2):81-3. Related Articles, Links

Parathyroid hormone related protein is localized in the granular layer
of normal skin and in the dermal infiltrates of mycosis fungoides but
is absent in psoriatic lesions.

Juhlin L, Hagforsen E, Juhlin C.

Department of Dermatology, University Hospital, Uppsala, Sweden.

Biopsies of normal and diseased skin were immunohistochemically
investigated for the presence of parathyroid hormone-related protein
(PTH-rp). In normal skin and several skin disorders a monoclonal
antibody against the 34-68 sequence of PTH-rp was found to be
exclusively located in the granular layer. PTH-rp could not be detected
in untreated psoriatic plaque lesions even when a granular layer was
present. Psoriatic lesions improving after 1-2 weeks' treatment with
betamethasone or vitamin D3 analogue revealed PTH-rp reactivity just
above the granular layer. These findings substantiate a possible role
for PTH-rp as a growth inhibitor. In the dermis the granular layer in
the upper part of the hair follicles was stained for PTH-rp and the
dermal infiltrates in 5 of 10 patients were stained with mycosis
fungoides.

PMID: 1350411

Whats been said in the group?
http://groups.google.com/groups?q=pth+psoriasis&qt_s=Search

******

The next abstract is regarding another immunomodulator,
neopterin.

http://groups.google.com/groups?q=+psoriasis+neopterin&qt_s=Search

Whoops forgot the abstract,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10954208
Serum neopterin as an objective marker of psoriatic disease activity.

Sanchez-Regana M, Catasus M, Creus L, Umbert P.

Department of Dermatology, Hospital Sagrado Corazon, Teaching Unit of
University of Barcelona, Spain.

Neopterin is a non-specific marker of the activation of cell-mediated
immunity. Several studies have demonstrated the crucial role of CD4+ T
cells in the pathogenesis of psoriasis. We have measured serum and
urine neopterin levels and urine neopterin/creatinine ratios by
radioimmunoassay in 24 patients with plaque-type psoriasis before and
after a course of topical treatment with triamcinolone acetonide 0.1%
and coal tar 4%. Results were compared with a group of 20 healthy,
non-psoriatic volunteers. Serum neopterin levels were significantly
elevated in the psoriatic group compared with the control group
(p=0.001) and were significantly reduced after treatment (p=0.01).
There was a correlation between pretreatment serum neopterin levels and
psoriasis area and severity scores (PASI) (r=0.37, p=0.03) and also for
pretreatment neopterin/creatinine ratios and PASI scores (r=0.45,
p=0.01). These findings indicate that serum neopterin concentrations
reflect disease activity in psoriasis.

PMID: 10954208

This stuff goes back to 1992 as well,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1467282

Here are the labs on it,
http://www.labcorp.com/datasets/labcorp/html/chapter/mono/sr006400.htm
(...)
Additional Information

Neopterin, a pyrazinopyrinidine compound, is produced by macrophages
after induction by interferon gamma and serves as a marker of cellular
immune system activation. Measurable levels of neopterin have been
detected in both the serum and urine of patients suffering from various
types of malignancies and viral infections. Changes in neopterin
concentrations in serum or urine can predict complications such as
graft rejection in organ transplant recipients. Elevated neopterin
levels are found in autoimmune disorders such as rheumatoid arthritis
and systemic lupus erythematosus (SLE). Neopterin levels can be used as
prognostic predictors for certain types of malignancies. Measurement of
neopterin levels has particular value for monitoring patients infected
with HIV. Neopterin is eliminated primarily in the urine, so evaluation
of urinary neopterin levels may be useful in assessing activation of
the cellular immunity system even in the absence of typical clinical
symptoms, since a correlation has been observed with the course of
diseases involving cellular immunity activation and urinary neopterin
levels.

*****************

This next one has me totally stumPed.

These chinese herbs and pills are hard to find on the web.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16152837
[Observation on effect of pifubing xuedu pill combined with diyin
tablet in treatment of psoriasis]

[Article in Chinese]

Yang DQ, Jiang YF, Zhang Y.

The 107th Hospital of PLA, Shandong. ytyd...@sina.com

OBJECTIVE: To observe the clinical effect of Pifubing Xuedu Pill (PXDP)
combined with Diyin Tablet (DYT) in treating patients with psoriasis.
METHODS: Sixty patients were divided into 2 groups by randomized
controlled method. DYT was orally taken by all patients, while XDP was
given additionally to patients in the treated group, the medication was
continued for 1 month. The therapeutic effect, toxic and adverse
reaction were observed. RESULTS: In the treated group, 7 patients were
cured, 11 basically cured, 4 markedly effective, 7 improved, and 1
ineffective, with the clinical cured rate of 60.0% and the total
effective rate 73.3%. In the control group, 3 were cured, 4 basically
cured, 9 markedly effective, 10 improved, and 4 ineffective, with the
clinical cured rate of 23.3% and the total effective rate 53.3%. No
significant difference was shown in comparison of the total effective
rate between the two groups (chi2 = 0.27, P > 0.05), however,
significant difference was shown in comparison of the clinical cured
rate (chi2 = 6.48, P < 0.05) between them. The toxic and adverse
reaction in the treated group was obviously lower than those in the
control group (t = 5.27, P <0.05). CONCLUSION: DYT combined with PXDP
in treating psoriasis shows better therapeutic effect, with quicker
initiation, lesser toxic and adverse reaction, and higher efficacy than
using DYT alone.

PMID: 16152837

randall... Fire in the adrenals was what i found in a chinese medicine
book for P!

randall

unread,

Sep 16, 2005, 12:46:04 PM9/16/05

Hi,

After yesterday's parathyroid news i'm starting to get
paranoid that my new found clearings may reverse in the
face of my current trials.

NOT!

More news from pubmed. From the last 24 hours.

Tracking genes and proteins first.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16163348
Psoriasis-like skin disease and arthritis caused by inducible epidermal
deletion of Jun proteins.

Zenz R, Eferl R, Kenner L, Florin L, Hummerich L, Mehic D, Scheuch H,
Angel P, Tschachler E, Wagner EF.

Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030
Vienna, Austria.

Psoriasis is a frequent, inflammatory disease of skin and joints with
considerable morbidity. Here we report that in psoriatic lesions,
epidermal keratinocytes have decreased expression of JunB, a gene
localized in the psoriasis susceptibility region PSORS6. Likewise,
inducible epidermal deletion of JunB and its functional companion c-Jun
in adult mice leads (within two weeks) to a phenotype resembling the
histological and molecular hallmarks of psoriasis, including arthritic
lesions. In contrast to the skin phenotype, the development of
arthritic lesions requires T and B cells and signalling through tumour
necrosis factor receptor 1 (TNFR1). Prior to the disease onset, two
chemotactic proteins (S100A8 and S100A9) previously mapped to the
psoriasis susceptibility region PSORS4, are strongly induced in mutant
keratinocytes in vivo and in vitro. We propose that the abrogation of
JunB/activator protein 1 (AP-1) in keratinocytes triggers
chemokine/cytokine expression, which recruits neutrophils and
macrophages to the epidermis thereby contributing to the phenotypic
changes observed in psoriasis. Thus, these data support the hypothesis
that epidermal alterations are sufficient to initiate both skin lesions
and arthritis in psoriasis.

PMID: 16163348

All they need to do is show how these Jun bugs get deleted in the
psoriatic then? Is it a fungus that uwe and cruiser have figured out
how to block or a simple gene deletion? Or polymorphism?

http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=polymorphism&qt_g=1&searchnow=Search+this+group

So, forget the gut, it starts in the skin? Why? Is it just a vitamin
D/calcium pathway mistake?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16162035
The Vitamin D3 Pathway in Human Skin and its Role For Regulation of
Biological Processes.

Lehmann B.

Dresden University of Technology, Medical School.

The skin is the only tissue yet known in which the complete UVB-induced
pathway fom 7-dehydrocholesterol to hormonally active calcitriol
(1alpha,25-dihydroxyvitamin D3, 1alpha,25(OH)2D3) occurs under
physiological conditions. Epidermal synthesis of calcitriol could be of
fundamental relevance because calcitriol regulates important cellular
functions in keratinocytes and immunocompetent cells. Because of their
antiproliferative and prodifferentiating effects, calcitriol and other
vitamin D analogs are highly efficient in the treatment of psoriasis
vulgaris. The known antipsoriatic effect of UVB light could, at least
in part, be mediated via UVB-induced synthesis of calcitriol. In
addition, mounting evidence indicates now that cutaneous vitamin D3
synthesis is of high importance for the prevention of a broad variety
of diseases, including various malignancies. New but controversially
discussed sun-protection guidelines were established for the prevention
of internal cancers. A better understanding of the metabolism of
vitamin D in the skin opens new perspectives for therapeutic
applications of vitamin D analogs.

PMID: 16162035

Yet we have increased ideas to beat back the skin fired plaques.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16161960
[Exploring new therapeutic approaches to the treatment of inflammatory
disorders--lipoxins]

[Article in Polish]

Jarmakowska K, Kuna P.

Klinika Pneumonologii i Alergologii Instytutu Medycyny Wewnetrznej
Uniwersytetu Medycznego w Lodzi.

The prevalence of inflammatory disorders continues to increase and its
optimal treatment still remains a challenge. Lipoxins, endogenous
eicosanoids biosynthesised in vivo at inflammatory sites, are potent
anti-inflammatory mediators. Therefore, it is of interest to
investigate the potential effects of lipoxins that could attenuate
chronic inflammation. Currently, only limited data on the effects of
lipoxins in clinical investigations are available. Nevertheless,
lipoxins caused inhibition of hyper-responsiveness and allergic airway
inflammation in asthma. They could also impact the progression of
inflammatory arthritides through the reduction of the inflammatory
infiltrates and limiting tissue destruction. Lipoxins may play
important anti-inflammatory roles in intestinal inflammation as well as
in a number of cutaneous inflammatory disorders like psoriasis or
atopic dermatitis. Taken together, the available data suggests that
lipoxins may have broad therapeutic potential in inflammatory disorders
and could provide an alternative to corticosteroids in certain clinical
settings.

PMID: 16161960

Ok, ok... so the white willow bark (aspirin) mixed with Cod liver oils
(CLO) is
the answer?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12471142
An aspirin-triggered lipoxin A4 stable analog displays a unique topical
anti-inflammatory profile.

Schottelius AJ, Giesen C, Asadullah K, Fierro IM, Colgan SP, Bauman J,
Guilford W, Perez HD, Parkinson JF.

Research Business Area Dermatology, Research Laboratories, Schering AG,
Berlin, Germany.

Lipoxins and 15-epi-lipoxins are counter-regulatory lipid mediators
that modulate leukocyte trafficking and promote the resolution of
inflammation. To assess the potential of lipoxins as novel
anti-inflammatory agents, a stable 15-epi-lipoxin A(4) analog,
15-epi-16-p-fluorophenoxy-lipoxin A(4) methyl ester (ATLa), was
synthesized by total organic synthesis and examined for efficacy
relative to a potent leukotriene B(4) (LTB(4)) receptor antagonist
(LTB(4)R-Ant) and the clinically used topical glucocorticoid
methylprednisolone aceponate. In vitro, ATLa was 100-fold more potent
than LTB(4)R-Ant for inhibiting neutrophil chemotaxis and
trans-epithelial cell migration induced by fMLP, but was approximately
10-fold less potent than the LTB(4)R-Ant in blocking responses to
LTB(4). A broad panel of cutaneous inflammation models that display
pathological aspects of psoriasis, atopic dermatitis, and allergic
contact dermatitis was used to directly compare the topical efficacy of
ATLa with that of LTB(4)R-Ant and methylprednisolone aceponate. ATLa
was efficacious in all models tested: LTB(4)/Iloprost-, calcium
ionophore-, croton oil-, and mezerein-induced inflammation and
trimellitic anhydride-induced allergic delayed-type hypersensitivity.
ATLa was efficacious in mouse and guinea pig skin inflammation models,
exhibiting dose-dependent effects on edema, neutrophil or eosinophil
infiltration, and epidermal hyperproliferation. We conclude that the
LXA(4) and aspirin-triggered LXA(4) pathways play key anti-inflammatory
roles in vivo. Moreover, these results suggest that ATLa and related
LXA(4) analogs may have broad therapeutic potential in inflammatory
disorders and could provide an alternative to corticosteroids in
certain clinical settings.

PMID: 12471142

These AA/hete pathways have been known at least as long as this
abstract back
in 1989.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2514125
Biosynthesis, catabolism, and biological properties of HPETEs,
hydroperoxide derivatives of arachidonic acid.
The oxygenation of arachidonic acid by lipoxygenases results in the
formation of HPETEs (hydroperoxyeicosatetraenoic acids), the first
products of the LOX pathway. These compounds are short lived and are
catabolised into various families of more stable compounds of which the
HETEs, hepoxilins, lipoxins and leukotrienes have been identified so
far. The development of new techniques have helped to identify and
understand the structures of various HPETEs and only recently the
biological effects of HPETEs and their various catabolites are being
unraveled. Although lipoxygenases are ubiquitous, not all tissues
possess the same spectrum of lipoxygenase enzymes. Hence different
HPETEs can be formed in different tissues. Recent studies have revealed
that HPETEs or products derived from them possess a diversity of
important biological properties including the regulation of electrolyte
flux and eicosanoid and corticosterone syntheses, release of histamine,
regulation of oocyte maturation and release of various reproductive
hormones. HPETEs appear to be involved in some pathological conditions
viz, skin psoriasis, Clarkson's disease, nerve injury and spinal cord
ischemia. These novel eicosanoids are associated with the release of
insulin as well as renin. Recently HPETEs have been suggested to act as
second messengers in the Aplysia sensory neurons and its catabolite,
hepoxilin, has been demonstrated to have effects on mammalian
hippocampal neurons. The purpose of this review is to provide a brief
summary of the formation of the HPETEs and the various families of
compounds derived from them as well as the various types of biological
activities for these products described so far.

PMID: 2514125

http://groups.google.com/groups?q=hete+arachidonic+psoriasis&qt_s=Search

And add in lipox and hpete's,
http://groups.google.com/groups?q=hpete+arachidonic+psoriasis+lipoxygenase&

And do the web search on the same,
http://www.google.com/search?q=hpete%20arachidonic%20psoriasis%20lipoxygenase&sa=N&tab=gw

And narrow it with P450
http://www.google.com/search?hl=en&lr=&q=hpete+arachidonic+psoriasis+lipoxygenase+p450&btnG=Search

And finally add the LPS,
http://www.google.com/search?hl=en&lr=&q=hpete+lps+arachidonic+psoriasis+lipoxygenase+p450&btnG=Search

And that takes us back to the gut?

So, the gut and skin are linked in psoriasis?

http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=lps+gut+liver&qt_g=1&searchnow=Search+this+group

And you thought it was in your jeans? lol

Or the bug in the gut like H. pylori for ulcers already?

randall... how do you eliminate lps from this picture? IP6/Vitamin C ?

randall

unread,

Sep 19, 2005, 12:51:46 PM9/19/05

Hi,

Our last p news post had the abstract from vienna regarding
etiology of P and lack of JunB proteins.

You'd think that the news wires would be sizzling over
this huge story.

Here it is. One giant news story today so far.
Of mice and men with P no less.

http://www.boston.com/news/globe/health_science/articles/2005/09/19/skin_diseases_origins_uncovered_through_mice/
Skin disease's origins uncovered through mice

September 19, 2005

PSORIASIS

Psoriasis, a chronic skin disease that afflicts 4.5 million people in
the United States with patches of inflamed skin topped with silvery
scales, has long perplexed scientists. Is it a skin disease or a
symptom of an immune system gone awry? European researchers knocked out
a few genes in lab mice and found that they could replicate the
hallmark skin plaques and arthritic lesions of psoriasis on mouse paws
and ears. Then, they tried knocking out the same genes in mice with
weakened immune systems to see if the body's defense system plays a
role in the disease. They found that even without certain immune cells,
mice developed symptoms of psoriasis.

BOTTOM LINE: The study resolves a longstanding controversy over the
origins of psoriasis. Some scientists thought the disease started
inside the body, as an immune system problem that caused skin cells to
turn over too quickly, forcing layers of skin to build up in itchy
lesions. The new study shows that the disease is more likely a skin
disorder that also has immune effects.

CAUTIONS: ''Nothing is black and white in biology," said study
co-author Erwin F. Wagner of the Research Institute of Molecular
Pathology in Austria. The study shows that psoriasis is primarily a
skin disease, but the immune system can't be taken out of the picture
completely. Mice with a weakened immune system fared better, not
suffering the bone destruction, joint inflammation, and arthritic
lesions that struck the mice with normal immune systems. This suggests
that psoriasis, though largely a skin disorder, is influenced by a
complex interplay of genes and immune cells.

WHAT'S NEXT: Scientists will study the gene that they used to trigger
the disease in the lab mice as a possible target for medications. They
will also use their mouse model -- the first one to replicate many of
the symptoms of the disease -- to study possible therapies and learn
more about the disease.

WHERE TO FIND IT: Nature, Sept. 15, 2005

I found the press release for nature. It has a nice shot of what
normal JunB or is is C, looks like,
http://www.imp.univie.ac.at/events/wagner_nature/Psoriasis_eng.pdf

Oh wait, just found the whole story in Nature. Did I post this
already? It looks familiar. Maybe I saw it but didn't post it?

Oh well, here it is, again or not,
http://www.nature.com/nature/journal/v437/n7057/full/nature03963.html

After looking at it, it's no wonder the news media doesn't know
how to report the orgins of the heartbreak of P without cautions
and the above pablum.

Maybe i'll take the time to repost the whole nature article here?

**************

P is in our genes then?

In your skin or in your gut genes? But whats the link?
http://www.healthcentral.com/newsdetail/408/527779.html

SUNDAY, Sept. 18 (HealthDay News) - People with inflammatory bowel
disease (IBD) are also more prone to severe respiratory and nervous
system disorders, according to two new studies in Gastroenterology.

IBD includes a number of chronic ailments such as ulcerative colitis
and Crohn's disease.

The first study found a nearly twofold increased risk of multiple
sclerosis in IBD patients. The researchers from the University of
Pennsylvania also linked IBD to optic neuritis and other neurological
disorders.

In the second study, Canadian researchers at the University of Manitoba
found that IBD patients have a significantly increased prevalence of
asthma, bronchitis, arthritis and psoriasis.

"These studies remind us that the effects of inflammatory bowel
disorders extend to every corner of the body, including the lungs and
central nervous system," said Dr. Edward V. Loftus Jr., author of an
accompanying editorial and an associate professor of medicine at the
Mayo Clinic College of Medicine.

"The findings lend credence to the concept that patients with one
chronic inflammatory condition are more likely than the general
population to develop another," Loftus concluded.

More information
The National Institutes of Health has more about Crohn's disease
http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/index.htm

I wonder if the caco-2 genes trigger the JunB genes from the Gi
tract?

Could the IP6/vitamin C trial i'm doing be having a positive effect on
creating more JunB proteins?

Time will tell and my skin is looking nice enough to still hang
out in sandals sans socks in shorts. :)

How long will my bliss last?

^^^^^^^^^^^^^^

http://www.newswire.ca/en/releases/archive/September2005/19/c1138.html
Welichem Biotech Inc. granted Australian Patent for compounds treating
autoimmune/inflammatory diseases

VANCOUVER, Sept. 19 /CNW/ - Welichem Biotech Inc. (TSX-V:WBI) ("the
Company") announced today that the Australian Patent Office has granted
the
Company a patent (No.780700) covering compounds in the WBI-1000 series
that
are useful in the treatment of inflammatory/auto-immune diseases such
as
psoriasis and inflammatory bowel disease.
A total of 16 claims covering novel compounds, pharmaceutical
composition
and use were granted with a term lasting to December 2019. This is the
first
patent issued for the Company's WBI-1000 series of compounds in a
cluster of
national applications pending in jurisdictions including Australia,
Canada,
China, Europe, Japan, Korea and the United States.
"This latest patent strengthens the Company's growing proprietary
position in pre-targeted therapies that seek to address unmet medical
needs in
inflammatory/autoimmune diseases," said John Webster, President & CEO
of
Welichem. "It also provides intellectual property protection for our
lead
product, WBI-1001, part of a group of pharmaceutical compounds from
symbiotic
organisms that have great potential to treat a number of diseases and
disorders," he added. The Company currently plans to begin formal
clinical
testing of the drug in early 2006.

^^^^^^^^^^

Great a butt skin cream. Cover's all bases. lol

randall... P is still a royal pain in the rear end.

randall

unread,

Sep 24, 2005, 4:50:23 PM9/24/05

randall wrote:

>http://www.boston.com/news/globe/health_science/articles/2005/09/19/skin_diseases_origins_uncovered_through_mice/

>
> Oh well, here it is, again or not,
> http://www.nature.com/nature/journal/v437/n7057/full/nature03963.html
>

> P is in our genes then?
>

YES! And new studies are coming out in tandem with this.

Those nice mice P models are already turning uP Possible P genes.
Thanks to Dr. Ann Bowcock. (The woman's an angel already)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16179734
The tetratricopeptide repeat domain 7 gene is mutated in flaky skin
mice: a model for psoriasis, autoimmunity, and anemia.

Helms C, Pelsue S, Cao L, Lamb E, Loffredo B, Taillon-Miller P, Herrin
B, Burzenski LM, Gott B, Lyons BL, Keppler D, Shultz LD, *Bowcock AM*.

Department of Genetics, Washington University School of Medicine, 4566
Scott Avenue, St. Louis, MO 63110. bow...@genetics.wustl.edu.

The flaky skin (fsn) mutation in mice causes pleiotropic abnormalities
including psoriasiform dermatitis, anemia, hyper-IgE, and anti-dsDNA
autoantibodies resembling those detected in systemic lupus
erythematosus. The fsn mutation was mapped to an interval of 3.9 kb on
chromosome 17 between D17Mit130 and D17Mit162. Resequencing of known
and predicted exons and regulatory sequences from this region in
fsn/fsn and wild-type mice indicated that the mutation is due to the
insertion of an endogenous retrovirus (early transposon class) into
intron 14 of the Tetratricopeptide repeat (TPR) domain 7 (Ttc7) gene.
The insertion leads to reduced levels of wild-type Ttc7 transcripts in
fsn mice and the insertion of an additional exon derived from the
retrovirus into the majority of Ttc7 mRNAs. This disrupts one of the
TPRs within TTC7 and may affect its interaction with an as-yet
unidentified protein partner. The Ttc7 is expressed in multiple types
of tissue including skin, kidney, spleen, and thymus, but is most
abundant in germinal center B cells and hematopoietic stem cells,
suggesting an important role in the development of immune system cells.
Its role in immunologic and hematologic disorders should be further
investigated.

PMID: 16179734

Who knew these P mice were so nice? and cool? and we will be looking
good
sooner then later.

I guess we should credit the whole team of folks that are working in
these
area's. Thanks Guys and Gals!

On to toPical questions that have been asked in this group.

What haPPens in the gut when you take FAE's?

Good question as they aren't clear as to their pathways. But we know
they work.

Here's an interesting abstract considering all the NAC
(N-acetyl-L-cysteine) talk and posts recently.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16177962
Evidence of covalent interaction of fumaric acid esters with sulfhydryl
groups in peptides.

Frycak P, Zdrahal Z, Ulrichova J, Wiegrebe W, Lemr K.

Department of Analytical Chemistry, Faculty of Science, Palacky
University, Olomouc, Czech Republic.

Fumaric acid esters, namely dimethylfumarate, have been used for the
treatment of psoriasis for many years. Still, their mode of action is
not fully clear. Because addition of nucleophiles to the double bonds
of fumarates can occur (Michael analogous addition), a study of the
interaction of fumarates with cysteine and cysteine-containing peptides
possessing nucleophilic sulfhydryl group was carried out. Experiments
were performed in aqueous medium at pH 7.4 and at 37 degrees C to
simulate physiological conditions. It was proven by mass spectrometric
measurements using an ion-trap and time-of-flight instrument that a
covalent bond can form between fumarates and the sulfhydryl group of
cysteine or cysteinyl residues in peptides. Structures of the
interaction products were elucidated by multistage mass spectrometry
applying collision-induced dissociation. Higher reactivity of
dimethylfumarate in comparison to monomethylfumarate and fumaric acid
was observed. Copyright (c) 2005 John Wiley & Sons, Ltd.

PMID: 16177962

Ok. So FAE and cysteine form covalent bonds in the gut. What does
that do as far as psoriasis is concerned?

I hope it clears us. I wish i could try some FAE right now.

On to angiogenic things and P!

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16176284
Vascular endothelial growth factor 121 is the predominant isoform in
psoriatic scales.

Zhang Y, Matsuo H, Morita E.

Department of Dermatology, School of Medicine, Shimane University,
Izumo, Japan.

Zhang Y, Matsuo H, Morita E. Vascular endothelial growth factor 121 is
the predominant isoform in psoriatic scales.Abstract: Vascular
endothelial growth factor (VEGF) is a powerful agent that causes
hyperpermeability of blood vessels as well as endothelial cell
proliferation. Recent investigations have revealed that production of
VEGF increases in epidermis of psoriatic lesions, and the overproduced
VEGF plays an important role in the pathogenesis of psoriasis. In this
study, we used immunohistochemical staining as well as extraction of
stratum corneum with physiological saline to further analyse VEGF
produced in psoriatic lesions. Biological activity of VEGF in the
psoriatic scales was assayed by cultured human umbilical vein
endothelial cells in vitro. The immunohistochemical examination
confirmed an increased production of VEGF in the keratinocytes of
psoriatic lesions. In addition, we found that the content of VEGF
contained in the psoriatic scales was approximately 50 times greater
than that in normal stratum corneum. We also found that VEGF 121
isoform, which has an exclusive ability to cause hyperpermeability of
blood vessels, was predominantly detected in psoriatic scales,
suggesting a major role of VEGF 121 isoform on the altered structure of
microvessels in psoriatic lesions.

PMID: 16176284

I guess this begs a question or two. Where does VEGF121 come from?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16116163
Cutting edge: proangiogenic properties of alternatively activated
dendritic cells.

Riboldi E, Musso T, Moroni E, Urbinati C, Bernasconi S, Rusnati M,
Adorini L, Presta M, Sozzani S.

Unit of General Pathology and Immunology, Department of Biomedical
Sciences and Biotechnology, University of Brescia, Brescia, Italy;

Angiogenesis plays an important role in tissue remodeling and repair
during the late phase of inflammation. In the present study, we show
that human dendritic cells (DC) that matured in the presence of
anti-inflammatory molecules such as calcitriol, PGE(2), or IL-10
(alternatively activated DC) selectively secrete the potent angiogenic
cytokine vascular endothelial growth factor (VEGF) isoforms VEGF(165)
and VEGF(121). No VEGF production was observed in immature or
classically activated DC. Also, the capacity to produce VEGF was
restricted to the myeloid DC subset. When implanted in the chick embryo
chorioallantoic membrane, alternatively activated DC elicit a marked
angiogenic response, which is inhibited by neutralizing anti-VEGF Abs
and by the VEGFR-2 inhibitor SU5416. Therefore, alternatively activated
DC may contribute to the resolution of the inflammatory reaction by
promoting VEGF-induced angiogenesis.

PMID: 16116163

Looks like an area worth exPloring. But not right now.

randall...

> Great! a butt skin cream. Cover's all bases. lol

randall

unread,

Sep 27, 2005, 3:31:05 PM9/27/05

Hi,

In p news today... abstracts from the last day or two.

Maybe soon the scientists will enlist cruiser to do a supplement trial.

First its diet,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16181450
Diet and psoriasis: experimental data and clinical evidence.

Wolters M.

Nutrition Physiology and Human Nutrition Unit, Institute of Food
Science, University of Hannover, Wunstorfer Str. 14, D-30453 Hannover,
Germany.

Summary Psoriasis is considered as a T-cell-mediated inflammatory skin
disease which is characterized by hyperproliferation and poor
differentiation of epidermal keratinocytes. While susceptibility to
psoriasis is inherited, the disease is influenced by environmental
factors such as infections and stress. Diet has been suggested to play
a role in the aetiology and pathogenesis of psoriasis. Fasting periods,
low-energy diets and vegetarian diets improved psoriasis symptoms in
some studies, and diets rich in n-3 polyunsaturated fatty acids from
fish oil also showed beneficial effects. All these diets modify the
polyunsaturated fatty acid metabolism and influence the eicosanoid
profile, so that inflammatory processes are suppressed. Some patients
with psoriasis show an elevated sensitivity to gluten. In patients with
IgA and/or IgG antigliadin antibodies the symptoms have been shown to
improve on a gluten-free diet. The active form of vitamin D,
1,25-dihydroxyvitamin D(3), exhibits antiproliferative and
immunoregulatory effects via the vitamin D receptor, and thus is
successfully used in the topical treatment of psoriasis. In this
review, dietary factors which play a role in psoriasis are assessed and
their potential benefit is evaluated. Furthermore, the risk of
drug-nutrient interactions in psoriasis therapy is discussed.

PMID: 16181450

Here's one I didn't know about. Some drug for P?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16183548
Dobesilate in the treatment of plaque psoriasis.

Cuevas P, Arrazola JM.

Servicio de Histologia, Departamento de Investigacion, Hospital Ramon y
Cajal, Ctra. de Colmenar, km. 9.100, E-28034-Madrid - Spain.
pedro....@hrc.es.

Fibroblast growth factor (FGF)-mediated pathways participate in many of
the cellular events implicated in the pathogenesis of psoriasis. Thus,
targeting FGF signals may be potentially therapeutic in the treatment
of psoriasis. We report for the first time on a 43-year-old man with
chronic-type plaque psoriasis with a daily topical treatment of
dobesilate, a new FGF inhibitor. As early as at day 14, the patient had
cleared or achieved excellent improvement of psoriatic skin lesions.
Topical dobesilate offers the potential for treatment of plaque
psoriasis without atrophy or other local side effects associated with
the use of topical corticosteroids.

PMID: 16183548

http://www.daignet.de/media/Cuevas(2).pdf

That was interesting.

*************

Of scid mice and men with P, again,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16181457
Efficacy of the fully human monoclonal antibody MOR102 (#5) against
intercellular adhesion molecule 1 in the psoriasis-severe combined
immunodeficient mouse model.

Boehncke WH, Ochsendorf FR, Noll S, Urban M, Popp A, Waldherr D,
Haunschild J, Litzenburger T.

Department of Dermatology, Johann Wolfgang Goethe University, Frankfurt
am Main, Germany MorphoSys AG, Lena-Christ-Str. 48, 82152 Martinsried,
Germany.

Summary Background Psoriasis is considered as a chronic immune-mediated
disease characterized by inflammation and proliferation of the
epidermis. Objectives Targeting intercellular adhesion molecule 1
(ICAM-1) is an attractive therapeutic option as this molecule is
critically involved in leucocyte adhesion and extravasation as well as
in lymphocyte activation. Methods We have selected the fully human
monoclonal antibody MOR102 (#5) against ICAM-1 from the Human
Combinatorial Antibody Library (HuCAL((R))). This antibodies human 94
was tested for its ability to interfere with lymphocyte activation and
adhesion in vitro as well as for its antipsoriatic efficacy in vivo
using the psoriasis-severe combined immunodeficient (SCID) mouse model.
Results The antibody demonstrated efficient inhibition of lymphocyte
adhesion to ICAM-1 in vitro, with an IC(50) of approximately 0.4 microg
mL(-1) (3 nmol L(-1)). In addition, MOR102 (#5) reduced lymphocyte
proliferation in mixed lymphocyte cultures by approximately 50%. The in
vivo efficacy of MOR102 (#5) was tested on grafts derived from lesional
skin of patients with chronic plaque-stage psoriasis transplanted on to
SCID mice. Intraperitoneal injection of 10 mg kg(-1) of MOR102 (#5)
antibody every alternate day over a period of 4 weeks resulted in
reconstitution of orthokeratotic differentiation and a significant (P <
0.05) reduction in epidermal thickness as well as marked reduction in
the inflammatory infiltrate. Therapeutic activity may be related to the
targeting of ICAM-1 on keratinocytes and thus preventing efficient
activation of local T cells. Conclusions Based on the efficacy of the
fully human monoclonal antibody MOR102 (#5) shown in vitro as well as
in vivo in the psoriasis-SCID mouse model, initiation of clinical
studies is indicated.

PMID: 16181457

Isn't it amazing that once a mouse was designed to mimic a psoriatic,
that they
would start testing with them?

Amazing!

Science really does work.

And we learn how things work without having to use ourselves as lab
rats.

FAE's work for more then P,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16181464
Fumaric acid esters in necrobiosis lipoidica: results of a prospective
noncontrolled study.

I don't know what NL is. Lets find a picture.
http://images.google.com/images?svnum=10&hl=en&lr=&q=necrobiosis+lipoidica&btnG=Search

H'mmm looks like p without the flakes.

**********

And my favorite today and yours if you want to use an herb that the
pharma's
can't control,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16182537
Synthesis and structure-activity relationships of novel indirubin
derivatives as potent anti-proliferative agents with CDK2 inhibitory
activities.

Moon MJ, Lee SK, Lee JW, Song WK, Kim SW, Kim JI, Cho C, Choi SJ, Kim
YC.

Department of Life Science, Gwangju Institute of Science and
Technology, Gwangju 500-712, Republic of Korea.

Indirubin, an active ingredient of a traditional Chinese recipe Danggui
Longhui Wan, has been known as a CDK inhibitor competing with ATP for
binding to the catalytic site of cyclin-dependent kinases (CDKs). Since
CDKs, a group of serine/threonine kinases forming active heterodimeric
complexes with cyclins, are key regulators of the cell cycle
regulation, therapeutic interventions targeting CDKs have been
stimulated for the treatment of proliferative diseases, such as cancer,
psoriasis, and for the prevention of chemotherapy-associated side
effects, such as alopecia. A series of novel indirubin analogs was
synthesized and evaluated for anti-proliferative and CDK2 inhibitory
activities. Among the indirubin derivatives tested in the growth
inhibitions against several human cancer cell lines, 5-nitro, halide,
and bulky group containing acylamino substituted analogs showed high
anti-proliferative effects. Selected analogs showing potent
anti-proliferative activities were evaluated further in the CDK2 enzyme
assay, which resulted in the discovery of potent CDK2 inhibitors.

PMID: 16182537

http://my.webmd.com/content/article/104/107504.htm
April 18, 2005 -- The key chemical in a traditional Chinese herbal
medicine, danggui longhui wan, may prove useful against cancer, says a
study in Proceedings of the National Academy of Sciences of the United
States of America.

And from the groups,
http://groups.google.com/groups?hl=en&lr=&q=Danggui+Longhui+Wan&qt_s=Search

http://www.nature.com/ncb/press_release/ncb0599.html
The secrets of Chinese medicine: Unravelling how indirubin stops tumor
cell growth

Nature Cell Biology 1, pp 60 - 67

For centuries, traditional Chinese herbal medicines have been used to
treat a vast array of conditions. These medicines are usually a mixture
of many components and often it is not clear which ingredients are the
active ones or how they work. One such mixture is Danggui Longhui Wan,
an ancient and surprisingly effective treatment for several leukemias.

Recently, scientists have postulated that the active ingredient in
Danggui Longhui Wan is indirubin, the red coloured relative of the
indigo blue dye. Now, Laurent Meijer and colleagues at the C.N.R.S.,
Roscoff, France, reveal a molecular mechanism by which indirubin
appears to stop the uncontrolled growth of tumour cells.

They found that indirubin interacts with a class of proteins known as
cyclin dependent kinases. These enzymes lie at the heart of the
machinery that dictates whether-, and when a cell divides. When
indirubin binds to these kinases it blocks their activity and hence
halts cell division. Meijer's group have also determined the molecular
structure of a complex molecule comprised of cyclin dependent kinases
bound to indirubin. This structure sheds light on how exactly indirubin
is able to specifically impede the function of these enzymes but not
others like them. It is hoped that these insights into the way
indirubin - and, indeed, Danggui Longhui Wan - works may feed into
the search for better anticancer drugs.

More on indirubin,
http://www.nature.com/ncb/journal/v1/n1/abs/ncb0599_60.html

I found one picture of a daisy looking flower. That can't be this
stuff! lol

randall... the P train rolls down the tracks of our tears and fears.

randall

unread,

Oct 1, 2005, 6:02:23 PM10/1/05

Hi,

P news from around the world.

This first sniPPet was taken from motorsport.com and is about
a race track,

http://www.motorsport.com/news/article.asp?ID=202284&FS=NASCAR-CUP
(...)
"I thought the track was in really good shape. And I think it has
changed from last week. He said that they spent four days dragging
tires around the racetrack to get some rubber in the racetrack. The
track itself, there's nothing wrong with it other than being
aesthetically ugly when you look at it. It looks like it has a bad case
of _____psoriasis_____ or something. It's fast. There's nothing bad
about it. I like what he's done as far as grooving the bottom and the
top of turns one and two. Again, in addition to that, making sure the
bottom was grooved, which it wasn't before it was resurfaced or
whatever they call it. I thought that was good because it brings it
back to the old-style racing, only it's grippier. And, yes, that is a
word. I don't think there's anything wrong with the racetrack. But I do
believe, based off of what Humpy was saying, it was probably in better
shape for the Busch cars this week than the Cup cars last week."
<sniP>

Thats some fast track!
&
My p may be non-aesthetically pleasing but it sure is fast. lol

*****

On the other side of the world in the strait times, you forget about
burning fossil fuels. It's more about eating something in relationshiP
to
P.

http://www.nst.com.my/Current_News/NST/Friday/JustChill/20050929152034/Article/indexb_html

FRESH INGREDIENTS: Burdock for cleansing and healing
IN the last couple of years burdock root has been appearing in our
local markets. It is from China, and the root, usually a metre long, is
called ngau pong in Cantonese. For just RM3 you can take it home,
scrape the skin off it, cut up and boiled in soup with meat

The Japanese call it gobo and cook it julienned in a vegetable dish,
steamed with egg, simmered in stews or braised.

Burdock goes by the botanical name Arctium lappa, with the first word
derived from the Greek "arktos", which means a bear, referring to the
roughness of the little hooked prickles or burrs on the round heads of
purple flowers of the plant, and "lappa" which means to seize. The burr
adheres to everything it comes into contact with, particularly the
coats of animals.

A Swiss inventor named George de Mestral in the 1940s observed how the
burrs from the burdock plant had attached themselves to his clothes and
to his dog?s fur while he was out for a walk. He looked closely at the
hook-and-loop system of the seeds and decided it could be used to join
other things together. Thus velcro was born.

Seriously, burdock has always been known as a medicinal plant. All
parts of it can be eaten for various health complaints.

Burdock root is a good source of manganese and phosphorous and is good
for the immune system. It is considered to be a diuretic and a blood
purifying agent. It has sugar lowering properties. It is also a mild
laxative and digestive.

It?s good for the kidneys, which probably explains why, after eating
stirfried julienned burdock root yesterday, I felt I had better bladder
control despite drinking a lot of water. It also helps to heal
cystitis.

Burdock root oil extract is actually used as a scalp treatment to
improve the strength and shine of hair, get rid of dandruff and promote
healing of skin.

Recent studies have found burdock root oil extract rich in
phytosterols and essential fatty acids (including rare long-chain
EFAs).

A dry and scaly skin as well as ezcema and psoriasis could benefit
from a decoction of burdock root, as well as eczema and psoriasis.

Burdock grows in hedges and ditches in Europe, parts of Asia and North
America. The Japanese cultivate it.

Here is a recipe for burdock root stirfried Japanese style with
carrot, mirin and soya sauce. It is delicious as a vegetable dish. You
could pair it with sliced grilled beef, roast chicken or roast pork,
put inside a soft roll or pita bread, and eat it for lunch or dinner.

Stirfried Burdock With Mirin

120g burdock (or 1/3 of the root)
1 medium-size carrot, cut into fine strips
1 1/2 Tbsps sesame oil
1 1/2 Tbsps mirin or cooking sake
3 tsps soya sauce
1/2 tsp sugar
2 tsps sesame seeds, pan roasted

Method
1. Choose a young burdock root. Scrape the skin off with a sharp knife
under water. It gives off a dark exudate in the water.
2. Cut the burdock into strips with a knife. Don?t use a vegetable
cutter as it will affect the texture and taste.
3. Put the burdock strips in a bowl of water. Drain in a colander when
you are about to cook them.
4. Heat sesame oil in pan. Add in the drained burdock and stir fry for
two minutes over a fairly high flame.
5. Add in the carrot strips and fry for a minute.
6. Add the mirin, soya sauce and the sugar.
7. Fry till the vegetables are without liquid, which should be quite
fast over a high flame. Dish out and serve topped with sesame seeds.

Note: You could use the rest of the burdock root to cook soup, or
simply put in a pot with water and boil for half an hour. Drink it to
cleanse the system.

randall: These guys are riPPing! I love their articles and reciPes. I
only
wish i was the one to discover that velcro thingy.

**************

We've had some posts recently where cancer (C) and P overlap.

The p53 gene has been posted in this group many times. Hence the
next two links,

The P53, viral (EBV) cancer link,
http://www.emaxhealth.com/51/3276.html

Researchers at the University of Toronto have mapped the molecular
details that show how a viral protein coded in the Epstein-Barr virus
immortalizes cells and causes them to continuously grow, thereby
predisposing people to certain types of cancer.

"Epstein-Barr virus (EBV) is one of the most common human viruses in
the world and is strongly linked to certain b-cell cancers like
Burkitt's lymphoma as well as the epithelial cell cancer,
nasopharyngeal carcinoma. EBNA1 is a protein coded in the Epstein-Barr
virus and suspected to play a role in the development of cancer," says
Lori Frappier, professor in medical genetics and microbiology at U of T
and senior author of a paper in the April 1 issue of Molecular Cell.

"This research shows how EBNA1 interferes with natural cell growth
regulation by binding to a particular protein in cells, causing them to
continue growing and therefore increasing the risk of becoming
cancerous."

Frappier explains that all cells contain the two proteins ? p53 and
USP7 ? that work together to regulate cell growth. P53 is an important
protein whose level in the cell determines whether cells will continue
to proliferate or stop dividing and die. USP7 is a protein that binds
to p53 and makes it stable. Under those conditions, cells stop growing
and die, which is a natural state of cell regulation. Once EBNA1 is
introduced to cells, however, this protein interferes with natural cell
regulation by binding to USP7 and preventing its interaction with the
p53 protein.
<snip>

http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-49254.html

Researchers at the University of Dundee have discovered new levels of
complexity in the regulation of the tumour suppressor gene p53,
findings which could have a significant impact on the identification of
patients at risk of developing aggressive cancer and in determining
more efficient drug treatments

*********************

Pubmed time.

Abstracts from the last few days,

The Zenon Technique.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16191851
Novel quantitative immunofluorescent technique reveals improvements in
epidermal cell populations after mild treatment of psoriasis.

van Duijnhoven MW, Hagenberg R, Pasch MC, van Erp PE, van de Kerkhof
PC.

Department of Dermatology, UMC St Radboud, Nijmegen, The Netherlands.

A novel antibody labelling technique, the Zenon technique, was used in
fluorescent immunohistochemistry for a better characterization of
epidermal cell populations in a quantitative approach. With this
technique, differences in proliferation and differentiation
characteristics were shown between psoriatic and normal epidermis. The
sensitivity of the method was investigated by assessing the effect of a
mild topical treatment versus an emollient.Frozen sections of
non-treated psoriatic epidermis and psoriatic epidermis treated once
daily with either an emollient or betamethasone-17-valerate for only 2
weeks were compared immunohistochemically. Antibodies against keratin
6, 10 and 15 were labelled with the Zenon technique, whereas antibodies
against the Ki-67 antigen and beta-1 integrin were covalently
FITC-labelled. Using image analysis, these markers were measured in the
epidermis in a standardized manner.Treatment of psoriasis with
short-term topical steroid resulted towards normalization of Ki-67
antigen, beta-1 integrin, keratin 10 and keratin 6 expression, which
are parameters for proliferation and differentiation. Although
treatment with an emollient showed hardly any clinical response,
changes towards a more normal phenotype could already be detected in
several epidermal markers using this method.

PMID: 16191851

Distinct HLA-C/KIR Genotype Profile Associates with Guttate Psoriasis.

Holm SJ, Sakuraba K, Mallbris L, Wolk K, Stahle M, Sanchez FO.

Unit of Dermatology, Department of Medicine, Karolinska Institutet,
Stockholm, Sweden.

Psoriasis is a multifactorial disease with a strong genetic background.
It associates strongly to HLA-Cw(*)0602. HLA-C interacts with killer
immunoglobulin-like receptors (KIR) on natural killer (NK) and some
natural killer-T (NKT) cells. KIR's function is triggered by specific
binding to HLA ligands, which depends on the amino acid 80 of the MHC
class I alpha-chain. This permits classifying all HLA-C alleles into
two functional groups: asparagine (N80) or lysine (K80) carrying
alleles. Psoriasis patients recruited at disease onset were categorized
as guttate, vulgaris without arthropathy and vulgaris with arthropathy
plus skin lesions. Patients and carefully matched controls were
genotyped for position 80 of HLA-C and for KIR. Based on possible
HLA/KIR combinations, individuals were classified according to expected
NK/NKT cell responses: balanced (B), excess inhibition (EI), excess
activation (EA), or undetermined (U). HLA-Cw6 and position 80
genotyping associated strongly to disease, whereas KIR2DS1 associated
weakly. Individuals of the U and EI classes were more common among
guttate psoriasis patients, which related to HLA-Cw(*)0602 status.
These results suggest that different levels for NK/NKT cell activation
thresholds, not only reduction, contribute to immune deregulation in
psoriasis. In the guttate phenotype, balanced HLA-C/KIR interactions
might be altered by the presence of concomitant streptococcal
infections.

PMID: 16185272

randall.. zenon my P so i stop looking like a fast track!

randall

unread,

Oct 4, 2005, 2:25:23 AM10/4/05

Hi,

P news:

New skin gene.

http://www.sciencedaily.com/releases/2005/10/051003232617.htm
Jefferson Scientists Identify Gene Defect Leading To Abnormal Skin
Development And Cancer

Researchers at Jefferson Medical College and at the Wadsworth Center in
New York have identified a gene defect in mice resulting in a range of
abnormalities, from cyclical hair loss and skin cancer to severe
problems in normal skin development. The work may lead to improved
treatments for skin injuries, including burns, and might have
implications for diseases such as eczema and psoriasis, as well as
certain cancers.

Linda Siracusa, Ph.D., associate professor of microbiology and
immunology at Jefferson Medical College of Thomas Jefferson University
in Philadelphia and at Jefferson's Kimmel Cancer Center and Bruce
Herron, Ph.D., a research scientist at the Wadsworth Center of the New
York State Department of Health and assistant professor in the
Department of Biomedical Sciences at the State University of New York
at Albany, wanted to identify the nature of an inherited genetic
mutation in mice called repeated epilation (Er), and pinpoint the gene
itself.

Mice carrying one copy of the mutation have cyclical hair loss, and
develop skin cancer late in life. Mice carrying two copies have severe
defects in skin development related to keratinocyte (skin cell)
differentiation. At birth, they lack external openings -- the nose and
mouth are covered by skin, for example -- and live only a brief time.

Previous studies had pinned the gene's location to mouse chromosome 4.
Reporting October 2, 2005 in the journal Nature Genetics, the research
team describes how it subsequently narrowed the region on chromosome 4
to about 800 megabases, eventually uncovering a mutation in a gene,
Stratifin. Stratifin is highly expressed in the epidermis and plays a
role in preventing human cancers. The researchers identified an
"insertion" mutation in the gene that resulted in a damaged Stratifin
protein.

"We looked at a number of inbred strains and only saw a mutation in the
Stratifin gene in mice with the Er features," Dr. Herron says. When the
Er mutation was "rescued" by providing a molecular carrier containing
normal genetic regions of chromosome 4, the mice had normal hair
development.

"We were interested in genes affecting susceptibility to the
development of skin cancer, and the Er mice provided a good model,"
says Dr. Siracusa. The initial goal of the work was to find out what
gene was responsible for the Er mutation.

"We think the mutation is potentially another player in what could be a
relatively novel pathway affecting the development of hair and skin,"
says Dr. Herron. The Stratifin gene is present in humans, and
comparable genetic defects are under investigation.

Drs. Siracusa and Herron's laboratories are continuing to collaborate
to understand the mechanisms behind the gene defect's effects on skin
development, hair growth and tumor development.

The researchers note that Stratifin is turned off in many cancers,
suggesting it may protect cells from becoming cancerous. The Stratifin
gene could help lead to a better understanding of the susceptibility to
and development of epithelial cancers such as those of the breast,
prostate, skin, lung, ovary and colon, and could predict a person's
response to cancer therapy. Further studies may also lead to
applications for hair loss treatment.

*****

Here's a stratifin abstract,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16120440
Stuff about P53 and <sniP> In keratinocytes, 14-3-3sigma (stratifin) is
involved in terminal differentiation and its cell cycle function in
this cell type might diverge from the one it fulfills in other cellular
backgrounds.

PMID: 16120440

Does it have something to do with P?

To early to tell or know I guess. There are 94 abstracts on pubmed, but
they
are all nearly concerned with cancer situations.

**************

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16190359

[Molecular abnormality in aging: its contribution to clinical
pathology]

[Article in Japanese]

Maruyama N, Ishigami A, Kondo Y.

Department of Molecular Pathology, Tokyo Metropolitan Institute of
Gerontology, Itabashi-ku, Tokyo 1730015.

During a survey of age-associated changes in the liver, we discovered a
novel protein SMP30. SMP30 expression decreased with aging due to
oxidative stress. We studied the effects of SMP30 on the plasma
membrane calcium pump. SMP30 enhances its activity. This finding
suggests that the decrease of SMP30 with aging induces cellular frailty
and various injuries. This frailty is one of the critical factors in
the development of senescence. To elucidate its role in senescence we
established a knockout. Its life span was shorter than the wild type.
The enzymatic functions of SMP30 have been reported. SMP30 is an
organophosphatase. SMP30 is also gluconolactonase having natural
substrates. This activity is associated with the pentose phosphate
pathway and the ascorbic acid synthesis pathway. These findings
indicate the pivotal role of SMP30. Another contribution of gerontology
to clinical pathology is citrullination. Citrullinated proteins are the
products of post-translational modification of the argine residues to
citrulline, catalyzed by a peptidylarginine deiminase (PADs) in a
calcium ion-dependent manner. We detected abnormal accumulation of
citrullinated proteins in the Alzheimer disease (AD) hippocampus, but
not in the normal brain. Two of the citrullinated proteins were
identified as a vimentin and GFAP. Type II PAD expression was enhanced
in the AD brain. Citrullinated protein could be a useful hallmark of
organ injuries. The physiological aspect of citrullinated proteins was
also recognized in epidermal differentiation. The normal epidermis
contains citrullinated proteins but not the epidermis affected by
____________psoriasis___________. This finding suggests that the
citrullination is critical for skin differentiation. The findings
observed in this aging study may contribute to clinical pathology.

PMID: 16190359

Senescence marker protein-30 as a novel antiaging molecule.

Feng D, Kondo Y, Ishigami A, Kuramoto M, Machida T, Maruyama N.

Department of Molecular Pathology, Tokyo Metropolitan Institute of
Gerontology, Tokyo 173-0015, Japan.

Senescence marker protein-30 (SMP30), composed of 299 amino acids, has
an approximate molecular mass of 32-34 kDa and has a pI 4.9 in charge.
The amino acid alignment from various animal species revealed a highly
conserved structure. SMP30 has an enzyme activity hydrolyzing sarin,
soman, and tabun, known as lethal toxic nerve chemicals. We analyzed
the organophosphatase activity of SMP30 using DFP as a substrate. This
DFPase activity is revealed in a dose-dependent manner in the presence
of magnesium ions. We investigated the intracellular localization of
SMP30. It is localized in both the cytoplasm and nucleus. To confirm
the presence of SMP30 in the nucleus, we prepared nuclear and
cytoplasmic extracts from isolated cultured hepatocytes. Western
blotting showed that SMP30 was detected in both extracts. Because the
expression is reduced by carbon tetrachloride, one can speculate that
the expression is modulated by oxidative stress increased with aging.

PMID: 15247044

http://www.pdg.cnb.uam.es/UniPub/iHOP/gs/94382.html

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

If you have allergies, hookworms may be an answer.

http://news.bbc.co.uk/1/hi/england/nottinghamshire/4294448.stm

Last Updated: Thursday, 29 September 2005, 14:10 GMT 15:10 UK

Volunteers wanted for worm study

The tiny worms would be injected into the bloodstream

Scientists are looking for volunteers to help them find a cure for
allergies - by injecting them with hookworms.

Researchers at Nottingham City Hospital need 60 volunteers who suffer
from allergies to carry hookworms.

The tests, based on research done in Africa, could help cure people
with
over-sensitive immune systems.

Doctors believe people carrying the parasite have a reduced risk of
allergies because their immune system is "distracted" by the worm.

Town asthma

John Britton, a professor of epidemiology at Nottingham City Hospital,
who has done research in Ethiopia, discovered people living in the
countryside are less likely to have allergies but more likely to have
parasites.

"We found higher levels of asthma in the towns and we believe this was
partly down to a lower number of people carrying parasites," he said.

I would also want to know a bit more about it before treatment like
that

Leshie Chandrapala, asthma sufferer

For the research, volunteers will receive 10 Papua New Guinea strains
of
the worm, which can grow up to a centimetre long.

"We are trying to find out if we can use the worms or their products to

lesson the impact of allergies," Prof Britton said.

"The worms pass into the bloodstream before being trapped in the lungs.

"They are then coughed up and swallowed into the stomach, then the
bowels, where they breed before the larvae pass out of the body. "

Researchers think some kinds of hookworm secrete proteins which can
damp
down the immune response that causes asthma.

Leshie Chandrapala, 25, from Forest Fields, who suffers from asthma,
said he would think twice before taking part in the tests.

"I find my asthma is often linked to stress and I have not been that
stressed recently," he said.

"I would also want to know a bit more about it before treatment like
that."

Researchers have already tested the worms on themselves to find the
appropriate dosage.
The 250,000 research project is looking for 30 asthma sufferers and 30
hayfever or allergy suffers for the 12-week trial

**********

randall... you've made your way from worm to man and much in you is
still...

randall

unread,

Oct 4, 2005, 12:43:26 PM10/4/05

Hi,

Biologicals in the news today.

Good news for PsA patients,

http://www.medadnews.com/News/index.cfm?articleid=277589
HUMIRA (Adalimumab) Receives FDA Approval for Treatment of Psoriatic
Arthritis

- Patients on HUMIRA Showed Substantial Improvement in Skin and Joint
Symptoms of the Disease -

ABBOTT PARK, Ill., October 04, 2005 /PRNewswire-FirstCall/ -- Abbott
announced today that the U.S. Food and Drug Administration (FDA)
approved HUMIRA(R) (adalimumab) for reducing signs and symptoms of
active arthritis in patients with psoriatic arthritis, a chronic
disease that combines the symptoms of arthritis, including joint pain
and inflammation, with those of psoriatic skin disease, such as dry,
scaly skin. Psoriatic arthritis (PsA) is a serious autoimmune disease
and few available treatment options address the potentially devastating
combination of symptoms affecting both the skin and joints. Psoriatic
arthritis is the first new disease indication for HUMIRA beyond
rheumatoid arthritis (RA) and is one of the five autoimmune diseases
Abbott is studying for HUMIRA therapy. <sniP>

& the abstract to go with it,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16200601
Adalimumab for the treatment of patients with moderately to severely
active psoriatic arthritis: Results of a double-blind, randomized,
placebo-controlled trial.

Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH,
Sharp JT, Ory PA, Perdok RJ, Weinberg MA.

Seattle Rheumatology Associates, Swedish Medical Center, Seattle,
Washington.

OBJECTIVE: Adalimumab, a fully human, anti-tumor necrosis factor
monoclonal antibody, was evaluated for its safety and efficacy compared
with placebo in the treatment of active psoriatic arthritis (PsA).
METHODS: Patients with moderately to severely active PsA and a history
of inadequate response to nonsteroidal antiinflammatory drugs were
randomized to receive 40 mg adalimumab or placebo subcutaneously every
other week for 24 weeks. Study visits were at baseline, weeks 2 and 4,
and every 4 weeks thereafter. The primary efficacy end points were the
American College of Rheumatology 20% improvement (ACR20) response at
week 12 and the change in the modified total Sharp score of structural
damage at week 24. Secondary end points were measures of joint disease,
disability, and quality of life in all patients, as well as the
severity of skin disease in those patients with psoriasis involving at
least 3% of body surface area. RESULTS: At week 12, 58% of the
adalimumab-treated patients (87 of 151) achieved an ACR20 response,
compared with 14% of the placebo-treated patients (23 of 162) (P <
0.001). At week 24, similar ACR20 response rates were maintained and
the mean change in the modified total Sharp score was -0.2 in patients
receiving adalimumab and 1.0 in those receiving placebo (P < 0.001).
Among the 69 adalimumab-treated patients evaluated with the Psoriasis
Area and Severity Index (PASI), 59% achieved a 75% PASI improvement
response at 24 weeks, compared with 1% of the 69 placebo-treated
patients evaluated (P < 0.001). Disability and quality of life measures
were also significantly improved with adalimumab treatment compared
with placebo. Adalimumab was generally safe and well-tolerated.
CONCLUSION: Adalimumab significantly improved joint and skin
manifestations, inhibited structural changes on radiographs, lessened
disability due to joint damage, and improved quality of life in
patients with moderately to severely active PsA.

PMID: 16200601

***********

P53 mentioned many times recently,
http://groups.google.com/groups?q=p53+psoriasis&start=0&scoring=d&

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16200332
Expression of p53 protein in psoriasis.

Baran W, Szepietowski JC, Machaj GS.

Department of Dermatology, Venereology and Allergology, Wroclaw Medical
University, ul.Chalubinskiego 1,50-368, Wroclaw, Poland.

INTRODUCTION: Psoriasis is characterized by hyperproliferation and
abnormal differentiation of keratinocytes,by the presence of
inflammatory cell infiltrate in both the dermis and the epidermis and
by alterations of capillaries. p53 protein is an important
transcription factor which plays a central role in cell cycle
regulation mechanisms and cell proliferation control. OBJECTIVES: This
study was performed to identify the expression and localization of p53
protein in lesional and non-lesional skin samples taken from psoriatic
patients in comparison with healthy controls. MATERIAL AND METHODS:
Sections of psoriatic lesional and non-lesional skin (n=18) were
examined. A control group (n=10) of healthy volunteers with no personal
and family history of psoriasis was also examined. The expression of
p53 was demonstrated using the avidin-biotin complex immunoperoxidase
method and the monoclonal antibody DO7. The count and localization of
cells with stained nuclei was evaluated using a light microscope in 10
fields for every skin biopsy. RESULTS: In lesional psoriatic skin the
count of p53 positive cells was significantly higher than in the skin
samples taken from healthy individuals (p<0.01) and non-lesional skin
taken from psoriatic patients (p=0.02). No significant difference
between non-lesional psoriatic skin and normal skin was observed
(p=0.1). A strong positive correlation between mean count and mean per
cent of p53 positive cells was found (p<0.0001). P53 positive cells
were located most commonly in the basal layer of the epidermis of both
healthy skin and non-lesional psoriatic skin. In lesional psoriatic
skin p53 positive cells were present in all layers of the epidermis.
CONCLUSION: P53 protein appears to be an important factor in the
pathogenesis of psoriasis.

PMID: 16200332

*******

Folate should be used with MtX all the time,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16198787
After examining the available data from the literature and drawing from
clinical experience, we advise folate supplementation for every patient
who receives methotrexate.

PMID: 16198787

********

Infliximab (remicade) for P as well as crohn's & arthritis et al,
http://groups.google.com/groups?q=infliximab&qt_s=Search

Infliximab for the treatment of psoriasis: clinical experience at the
State University of New York at Buffalo.

Kalb RE, Gurske J.

Department of Dermatology, School of Medicine and Biomedical Sciences,
State University of New York, Buffalo, New York, USA. ka...@buffalo.edu

BACKGROUND: Infliximab has shown promising results for the treatment of
moderate to severe psoriasis and psoriatic arthritis. METHODS: We
conducted a retrospective study of all 52 patients treated with
intravenous infliximab for severe psoriasis at a single practice site.
These patients had recalcitrant plaque psoriasis (>33% body surface
area), which was unresponsive to multiple conventional systemic
therapies. Intravenous infliximab was administered at a dose of 5 mg/kg
at 0, 2, 6, and 14 weeks and every 8 weeks thereafter. Patients were
monitored for infections, infusion reactions, side effects, and
response to therapy. RESULTS: Fifty-two patients (men = 32, women = 20)
with a mean age of 47 (range, 22-76 years old) were included in this
study. They were followed for a minimum of 4 months and a maximum of 33
months (median, 22 months). Patients received a mean total number of 12
infusions (range, 3-22). Forty-six of 52 patients (88%) had a clear or
almost clear improvement based on the Physician's Global Assessment
done by a single physician. Twelve patients (23%) required infliximab
dose escalation to maintain control of their disease. Nine patients
experienced infusion reactions. Thirteen patients experienced
nonopportunistic infections; however, only one infection required
temporary cessation of infliximab. LIMITATIONS: This was a
retrospective study at a single practice site. CONCLUSION: Infliximab
was extremely effective and well tolerated in this group of patients
with severe, recalcitrant psoriasis. Thirty-nine of 52 patients have
continued receiving treatment for a median duration of 25 months with
excellent disease control. Infliximab can provide control of extensive
psoriasis with continued intermittent infusions.

PMID: 16198781

******

randall.. fighting the good fight with biologicals

randall

unread,

Oct 4, 2005, 6:01:01 PM10/4/05

Hi,

http://news.biocompare.com/newsstory.asp?id=99834

New Immune Cell Found To Be A Key To Inflammatory Diseases
10/2/2005

Source: University of Texas M. D. Anderson Cancer Center

The molecular roots of inflammatory and autoimmune diseases such as
asthma, arthritis, and multiple sclerosis (MS) have been discovered by
a team of researchers led by The University of Texas M. D. Anderson
Cancer Center. They say their findings may point to ways to effectively
treat these diseases - if not stop them before they start.

In a lead article in the November issue of Nature Immunology (released
online on Oct. 2), the scientists report finding a novel type of "T
helper" cell they say is the culprit for initiating chronic
inflammation and autoimmunity in a variety of body tissues. This newly
described T cell - which they call inflammatory TH cells (or THi) -
produces interleukin 17 (IL-17), a potent cytokine that researchers
have already linked to an immune system gone awry.

"We suspected that IL-17 is a player in autoimmune and inflammatory
diseases, but we didn't understand where IL-17 came from before this
finding," says the study's lead investigator, Chen Dong, Ph.D., an
associate professor in the Department of Immunology.

"Now we have discovered the source of IL-17 and also have solidly
demonstrated that these are the crucial cells that regulate tissue
inflammation in autoimmune disease and asthma," he says. "These
findings suggest that shutting down the activity of these THi cells
might stop chronic inflammatory diseases from developing in the first
place."

He adds that while such drugs are years away from development and
clinical trials, agents that block IL-17 could represent an effective
treatment, based on these results.

Dong and four other M. D. Anderson researchers collaborated with
scientists from the University of Washington, the Institute for Systems
Biology in Seattle and Johns Hopkins School of Medicine.

While the findings have no immediate relevance to the field of
oncology, it is known that cancer can arise from inflammatory
processes. Further understanding of how the immune system functions,
and how it can go awry, is important, Dong says.

T cells are white blood cells that play a variety of roles in the
immune system, including the identification of foreign molecules in the
body, such as bacteria and viruses, and the activation and deactivation
of other immune cells.

T helper cells are specific T cells that have receptors that recognize
and bind to fragments (known as antigens) of the invaders that already
have been displayed on the surface of other immune system cells. (These
T helper cells are also called CD4 T cells since they express CD4
molecules.) Once the antigen has been bound, these T helper cells
become activated, and they morph into "effector" cells which then boost
an immune response by secreting "cytokine" molecules such as
interleukins and interferons.

Before this study, two such different types of effector T helper cells
had been known - type I (TH1), linked to the body's response to
microbial infection, and type 2 (TH2), which plays a crucial function
in production of B cell antibodies and also is associated with
development of allergies.

Although TH1 and TH2 are known to produce powerful cytokines - such as
interferon-gamma (IFN-g) and allergy-associated interleukin 4 (IL-4),
respectively - they are not inflammatory or associated with production
of IL-17, which sets off an errant immune response that results in
tissue inflammation.

Researchers could not understand the origins of such an inflammatory
response in body tissues. The only clue they had was that excess IL-17
molecules are found in arthritic joints, in lungs swollen by asthma and
in brain cells that lead to nerve degeneration and the onset of MS.
"But we didn't know which T cells were responsible for secreting
IL-17," Dong says. To find out where IL-17 came from, the researchers
designed a series of cell culture studies and mouse experiments. In
brief, they "educated" T helper cells to become IL-17 producing cells.
They found that IL-17 is triggered by a unique set of signals that now
define this new "lineage" of T helper cells. "They are completely
different from TH1 and TH2 effector cells," says Dong. They then used a
mouse model of MS and demonstrated that they could stop development of
the disease with an antibody agent that blocked IL-17. Finally, they
developed a transgenic mouse model of asthma and found that, by
producing excessive IL-17 in the lung, they were able to produce
asthmalike symptoms.

Dong says the researchers hypothesize that these newly discovered THi
cells travel to selected body tissues and release IL-17. This action,
in turn, stimulates expression of "chemokines," which results in a rush
of inflammatory cells into the tissue. Thus a chronic inflammatory
reaction is set up, he says.

The scientists don't know what initially sets off activation of the
newly discovered T helper cell in diseases such as arthritis and
asthma, Dong says. "We don't know why these dangerous helper T cells
are activated in the patients, but we now know how they function, and
that should take us a long way to understanding and treating these and
other inflammatory and autoimmune diseases."

***********************

Well, we haven't had much on IL-17. But we had some in the group,
http://groups.google.com/groups?q=il-17+psoriasis&qt_s=Search

At this time, this is the most current pubmed abstract,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15315354

**************************

IP6 is supposed to block iron.

Is this next story the reason why my IP6 trials are working so well?

http://www.nlm.nih.gov/medlineplus/news/fullstory_27161.html
Researchers have documented one of the mechanisms that disease-causing
bacteria use to thwart immune-system attacks against them, and it's
made of iron.

E. coli and other pathogens use a protein that contains an iron
molecule to trigger a genetic reaction to remove nitric oxide that's
trying to destroy the germs, the researchers wrote Thursday in the
journal Nature.

Nitric oxide is one of the main weapons that immune-system cells use
against invaders. The chemical breaks through cell walls to destroy
bacteria. But over the past few years, scientists have realized that
many bacteria, like E. coli, contain proteins on their surfaces that
allow them to neutralize the toxic effects of nitric oxide.

A number of scientists have been working to understand just how the
bacteria defend themselves and have focused on several candidates. The
new paper spells out one, although probably not the only, mechanism for
the disarmament.

"If we can interfere with the mechanism, it could lead to better
antibiotics and better treatments," said Stephen Spiro, a Georgia Tech
biologist who co-authored the paper with several scientists from
Britain's John Innes Centre.

Escherichia coli and its near relative, salmonella, are typically
transmitted to humans through undercooked meat, unwashed vegetables and
dirty utensils. Infections can cause diarrhea, stomach cramps and
sometimes more serious illness that can result in kidney damage and
even death.

The federal Centers for Disease Control and Prevention estimates that
the most dangerous strain of E. coli infects some 73,000 Americans each
year, sending about 2,100 to the hospital and resulting in at least 60
deaths.

E. coli usually doesn't respond to antibiotics, while salmonella has
developed several drug-resistant strains.

Spiro and his colleagues studied a harmless strain of E. coli, and
focused on a nitric-oxide-regulating protein called NorR. "It turns out
that NorR contains a single molecule of iron, and our study found that
the nitric oxide binds to the iron, which in turn activates the
protein," he explained.

Once the protein is switched on, it ramps up expression of genes that
in turn produce an enzyme that removes nitric oxide in large
quantities, allowing the bacteria to survive.

The researchers anticipate that by understanding how the bacteria first
responds to an onslaught of nitric oxide, they may eventually be able
to disrupt this alert system.

Manipulating nitric-oxide levels in the bloodstream is a dicey
proposition, since the gas is used to transmit signals between human
cells, but also controls inflammation and blood-vessel dilation.

So while some scientists have enjoyed success in using topical
therapies using nitric oxide to control infections on the skin and in
the mouth, internal use of the substance as a therapy has yet to be
worked out.

On the Net: http://www.nature.com

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

New stat info,
http://news.biocompare.com/newsstory.asp?id=99362
Engineered Molecule Amplifies Body's Immune Response

By altering a molecule called Stat1, which is involved in cellular
immune signaling, scientists have succeeded in making the molecule more
responsive and thus more efficient. This old protein with a new twist
may eventually be used to improve the body's defense against infection.

Stat1 is involved in immune responses that are initiated by proteins
called interferons. These proteins are produced by the cells of the
immune system in response to challenges by foreign agents such as
viruses, bacteria, parasites and tumor cells. Recently, interferon has
also been shown to play a role in the body's surveillance against the
development of cancer. Because of this role, recombinant interferon is
often used for the treatment of certain fibrotic diseases as well as
cancers.

Interferon binds to receptors on the surface of the cell, which then
use Stat molecules to send signals to the nucleus to increase the
expression of genes needed to defend the host against infection. A
balance in the amount of Stat signaling caused by interferon is very
important.

"When interferon levels are too low, the host is highly susceptible to
infection," explains Dr. Michael J. Holtzman of the Washington
University School of Medicine in St. Louis, Missouri. "This also
applies to Stat1. Children who are born with genetic deficiencies of
Stat1 are also very susceptible to infection. In the more severe case,
the children die in infancy of fatal viral infections. In less severe
cases, they later develop infections due to mycobacteria. When
interferon levels are too high, for example during treatment with
interferon, there are side effects due to the increased nonspecific
response caused by excessive amounts of interferon."

Dr. Holtzman and his colleagues at the Washington University School of
Medicine decided to try to improve the body's defense against infection
without causing side effects that occur with interferon treatment by
engineering a hyper-responsive Stat1 molecule. By increasing the
efficiency of the Stat1 molecule, the host could have the benefits of
increased Stat1 signaling even at the low levels of interferon normally
present in the body. Their results appear as the "Paper of the Week" in
the October 7 issue of the Journal of Biological Chemistry, an American
Society for Biochemistry and Molecular Biology journal.

"Our paper is really quite simple in conceptual terms," says Dr.
Holtzman. "It is well known that interferon provides a benefit to
people by protecting them against infectious diseases and cancer.
Unfortunately, administration of interferon is costly and short-lived
and has significant side effects. We simply reasoned that it might be
possible to improve the benefits of interferon by enhancing the way it
produces its beneficial effects. We therefore improved a molecule,
known as Stat1, that is responsible for relaying the benefits of
interferon in the body."

Their initial in vitro results were promising, and the engineered Stat1
molecule exhibited an increased responsiveness to interferon. Following
up on these discoveries, Dr. Holtzman and his colleagues are currently
performing gene transfer experiments, using both recombinant viruses
and transgenic mice, to establish the benefits of hyper-responsive
Stat1 in vivo for treating viral infection and cancer. They are also
screening for drugs that might increase Stat1 responsiveness.

These experiments may eventually lead to many improvements in cancer
therapy as well as the treatment of other infections. Basically, any
situation in which interferon hyper-responsiveness might be beneficial
will profit from Dr. Holtzman's research.

"One could use our strategy of improving Stat1 efficiency during the
winter months in patients who are at risk for developing serious viral
infections, for example children with asthma, or heart disease, or
immune compromise," suggests Dr. Holtzman. "It may also be of benefit
in situations where interferon therapy has been used, such as
treatments for liver disease and lung fibrosis, as well as certain
cancers. Improving Stat1 efficiency would allow for much lower doses of
interferon to be used, decreasing cost and side effect profile. In
terms of diagnosis, it may be possible to screen patients for the level
of Stat1 responsiveness to interferon, and if found to be low, that
would make them candidates for a strategy to improve Stat1
responsiveness using our methods."

******************

It would aPPear to me that things are going in the right direction.

randall... and the latest IP6 trial is A OK and nearly clear!

randall

unread,

Oct 5, 2005, 2:03:01 PM10/5/05

randall wrote:

> http://news.biocompare.com/newsstory.asp?id=99834
>
> New Immune Cell Found To Be A Key To Inflammatory Diseases
> 10/2/2005

<sniP>

> Well, we haven't had much on IL-17. But we had some in the group,
> http://groups.google.com/groups?q=il-17+psoriasis&qt_s=Search
>
> At this time, this is the most current pubmed abstract,
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15315354

This is Dong's abstract,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16200068
A distinct lineage of CD4 T cells regulates tissue inflammation by
producing interleukin 17.

( sidebar on cd4:
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/ClassIIpath.gif
)
&
http://groups.google.com/groups?q=cd4+T+cells+psoriasis&qt_s=Search )

Back to Dong's abstract as it ties to the article link from yesterday.

Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L,
Zhu Z, Tian Q, Dong C.

[1] Department of Immunology, University of Washington, Seattle,
Washington 98195, USA. [2] These authors contributed equally to this
work.

Interleukin 17 (IL-17) has been linked to autoimmune diseases, although
its regulation and function have remained unclear. Here we have
evaluated in vitro and in vivo the requirements for the differentiation
of naive CD4 T cells into effector T helper cells that produce IL-17.
This process required the costimulatory molecules CD28 and ICOS but was
independent of the cytokines and transcription factors required for T
helper type 1 or type 2 differentiation. Furthermore, both IL-4 and
interferon-gamma negatively regulated T helper cell production of IL-17
in the effector phase. In vivo, antibody to IL-17 inhibited chemokine
expression in the brain during experimental autoimmune
encephalomyelitis, whereas overexpression of IL-17 in lung epithelium
caused chemokine production and leukocyte infiltration. Thus, IL-17
expression characterizes a unique T helper lineage that regulates
tissue inflammation.

PMID: 16200068

While we've had many Th1/Th2 posts, this is a first for Thi,
http://groups.google.com/groups?q=th1%2FTh2+psoriasis&qt_s=Search

The focus seems to be IL-17 now,
http://pga.gs.washington.edu/data/il17/welcome.html
IL17:interleukin 17 (cytotoxic T-lymphocyte-associated serine esterase
8) Chromosomal Location: 6p12 <sniP>

What does this all mean?

Real scientists are at work,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16200070
Interleukin 17-producing CD4(+) effector T cells develop via a lineage
distinct from the T helper type 1 and 2 lineages. (aka-Th1/Th2)

Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM,
Weaver CT.

Department of Pathology, University of Alabama at Birmingham,
Birmingham, Alabama 35294, USA.

CD4(+) T cells producing interleukin 17 (IL-17) are associated with
autoimmunity, although the precise mechanisms that control their
development are undefined. Here we present data that challenge the idea
of a shared developmental pathway with T helper type 1 (T(H)1) or T(H)2
lineages and instead favor the idea of a distinct effector lineage we
call 'T(H)-17'. The development of T(H)-17 cells from naive precursor
cells was potently inhibited by interferon-gamma (IFN-gamma) and IL-4,
whereas committed T(H)-17 cells were resistant to suppression by T(H)1
or T(H)2 cytokines. In the absence of IFN-gamma and IL-4, IL-23 induced
naive precursor cells to differentiate into T(H)-17 cells independently
of the transcription factors STAT1, T-bet, STAT4 and STAT6. These
findings provide a basis for understanding how inhibition of IFN-gamma
signaling enhances development of pathogenic T(H)-17 effector cells
that can exacerbate autoimmunity.

PMID: 16200070

I've suspected for a long time that those who responded slowly to the
biologicals had other issues with IFN possibly,
http://groups.google.com/groups?q=interferon-gamma+psoriasis&qt_s=Search

That first hit has the link to duct taPe man!

For this to fit the randall's theory, it must pass the gut test.

IL-17 in the gut,
Interleukin-17 is a potent immuno-modulator and regulator of normal
human intestinal epithelial cell growth.

Schwartz S, Beaulieu JF, Ruemmele FM.

Children's Hospital, Mucosal Immunology Laboratory, University of Bonn,
Bonn, Germany.

Upregulation of the T-cell derived cytokine interleukin (IL-17) was
reported in the inflamed intestinal mucosa of patients with
inflammatory bowel disorders. In this study, we analyzed the effect of
IL-17 on human intestinal epithelial cell (HIEC) turnover and
functions. Proliferation and apoptosis in response to IL-17 was
monitored in HIEC (cell counts, [(3)H]thymidine incorporation method,
and annexinV-PI-apoptosis assay). Signalling pathways were analyzed by
Western blots, electromobility shift assay, and immunofluorescence
studies. IL-17 proved to be a potent inhibitor of HIEC proliferation
without any pro-apoptotic/necrotic effect. The growth inhibitory effect
of IL-17 was mediated via the p38 stress kinase. Consequently, the
p38-SAPkinase-inhibitor SB203580 abrogated this anti-mitotic effect. In
parallel, IL-17 provoked the degradation of IkappaBalpha, allowing
nuclear translocation of the p65 NF-kappaB subunit and induction of the
NF-kappaB-controlled genes IL-6 and -8. IL-17 potently blocks
epithelial cell turnover while at the same time amplifying an
inflammatory response in a positive feedback manner.

PMID: 16198312

Hey! I'm ok with this for now.

We have a controller of the controllers now with Thi over Th1/Th2's.

I wish i had a THi chart to update the one i've used a dozen times now,
http://www.iir.suite.dk/IIR/03Th/Th.htm

As Thi has to be figured into this last one. :)

We have gut control from IL-17 and stats? Caused by LPS?

Is this the final gut/skin connections?

Time will tell.

> **************************
>
> IP6 is supposed to block iron.
>
> Is this next story the reason why my IP6 trials are working so well?
>
> http://www.nlm.nih.gov/medlineplus/news/fullstory_27161.html
> Researchers have documented one of the mechanisms that disease-causing
> bacteria use to thwart immune-system attacks against them, and it's
> made of iron.
>
> E. coli and other pathogens use a protein that contains an iron
> molecule to trigger a genetic reaction to remove nitric oxide that's
> trying to destroy the germs, the researchers wrote Thursday in the
> journal Nature.
>
> Nitric oxide is one of the main weapons that immune-system cells use
> against invaders. The chemical breaks through cell walls to destroy
> bacteria. But over the past few years, scientists have realized that
> many bacteria, like E. coli, contain proteins on their surfaces that
> allow them to neutralize the toxic effects of nitric oxide.
>

<snip>

For those of you new to this game. NO was big around here a few years
back. Posts like NOnono, oh no etc lol,
http://groups.google.com/groups?q=nonono+psoriasis&qt_s=Search

No= nitric oxide and that caused you to say HELL NO to your P skin.
:(

And to get that you need LPS,
http://groups.google.com/groups?q=nonono+psoriasis+nitric+oxide+lps&qt_s=Search

> New stat info,
> http://news.biocompare.com/newsstory.asp?id=99362
> Engineered Molecule Amplifies Body's Immune Response

Ok, lets make it P real,
http://groups.google.com/groups?q=stat+lps+psoriasis&qt_s=Search

>
> By altering a molecule called Stat1, which is involved in cellular
> immune signaling, scientists have succeeded in making the molecule more
> responsive and thus more efficient. This old protein with a new twist
> may eventually be used to improve the body's defense against infection.
>
> Stat1 is involved in immune responses that are initiated by proteins
> called interferons. These proteins are produced by the cells of the
> immune system in response to challenges by foreign agents such as
> viruses, bacteria, parasites and tumor cells.

What about LPS? If it turns on Th1 (T helper 1 cells) what's the
relationship to IL-17 now?

Could this THi be of help?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12527339

Or do they need to figure out their Thi? lol

If it controls Th1/Th2, i would have to think that the role
of LPS will be revealed as to immune factors previously not understood.

Could a large piece of the p puzzle be within reach?

randall... hoPe so!

> Recently, interferon has
> also been shown to play a role in the body's surveillance against the
> development of cancer. Because of this role, recombinant interferon is
> often used for the treatment of certain fibrotic diseases as well as
> cancers.
>

<snip>

Cruiser

unread,

Oct 5, 2005, 3:44:10 PM10/5/05

Randall,

Very good information. Thanks.

> >
> > randall... and the latest IP6 trial is A OK and nearly clear!
>

I wonder if the IP6 has another role besides chelating iron.

I would guess that with six phosphate groups, it would act as a phosphate
donor.

It have been looking at the ATP, ADP cycle, and you need a phosphate donor
to reactivate ADP to ATP, since ATP gives up a phosphate group, when it
becomes ADP. Normally, that phosphate comes from creatine phosphate. ATP is
needed to make SAMe from homocysteine. There could be excess demand for
phosphate donors when the body is under stress.

Just a thought.

What all are you supplementing now?

You seem to be having very good success.

Cruiser

randall

unread,

Oct 5, 2005, 4:48:31 PM10/5/05

Cruiser wrote:
> Randall,
>
> Very good information. Thanks.
>

My pleasure as it keeps me up to date as well.

Then i can't help but think about it for a day or two.

It's all so counterintuitive. That IL-17 thing is good but
the IFN-gamma seems backwards to whats haPPening with us. :(

> > >
> > > randall... and the latest IP6 trial is A OK and nearly clear!
> >
>
> I wonder if the IP6 has another role besides chelating iron.
>
> I would guess that with six phosphate groups, it would act as a phosphate
> donor.
>
> It have been looking at the ATP, ADP cycle, and you need a phosphate donor
> to reactivate ADP to ATP, since ATP gives up a phosphate group, when it
> becomes ADP. Normally, that phosphate comes from creatine phosphate. ATP is
> needed to make SAMe from homocysteine. There could be excess demand for
> phosphate donors when the body is under stress.
>
> Just a thought.
>
> What all are you supplementing now?

I've been using half a gram of the jarrow formula. Let me get it,
https://secure.progesterone.com/web_store/product_info.php?cPath=34&products_id=152

I also can't help but feel that the vitamin C is augmenting the effects
in the gut of whatever it is that it's doing. I'm up to 3 grams with
each
meal. Most days that's one shake meal and one suPPer meal.

So, not more then 6 grams a day on average.

>
> You seem to be having very good success.
>

YeP! So keep your fingers crossed. I'm at the end of this trial so i'm
contemplating the next modifications.

I did pick up the trader joe's B-12. It is the cyano form. Oh well. I
did
check pubmed and couldn't find your complaints against it. So, till
the next bottle, which may be a year, i'll play around with the stuff
I've got. It's 100 count, so that at two a week is a cheap enough.

As to my current trial, one of the things that is different now
is my continuing use of glucosamine and chondroitin sulfate from
costco.com.

Never used that combo with vitamin C and IP6 before. Is that it?

Try it and let me know.

randall
> Cruiser

Pi

unread,

Oct 6, 2005, 10:45:52 AM10/6/05

On 4 Oct 2005 15:01:01 -0700, "randall" <ranh...@aol.com> wrote:
<snipalot>

>While the findings have no immediate relevance to the field of
>oncology, it is known that cancer can arise from inflammatory
>processes. Further understanding of how the immune system functions,
>and how it can go awry, is important, Dong says.

Is this known? Does an inflammatory process like Psoriasis give more
chance on cancer? I don't think so?

Pieter

Cruiser

unread,

Oct 6, 2005, 11:10:58 AM10/6/05

"randall" <ranh...@aol.com> wrote in message

news:1128545311....@z14g2000cwz.googlegroups.com...

>
> I've been using half a gram of the jarrow formula. Let me get it,
>
https://secure.progesterone.com/web_store/product_info.php?cPath=34&products_id=152
>
> I also can't help but feel that the vitamin C is augmenting the effects
> in the gut of whatever it is that it's doing. I'm up to 3 grams with
> each
> meal. Most days that's one shake meal and one suPPer meal.
>
> So, not more then 6 grams a day on average.
> >
> > You seem to be having very good success.
> >
>
> YeP! So keep your fingers crossed. I'm at the end of this trial so i'm
> contemplating the next modifications.
>
> I did pick up the trader joe's B-12. It is the cyano form. Oh well. I
> did
> check pubmed and couldn't find your complaints against it. So, till
> the next bottle, which may be a year, i'll play around with the stuff
> I've got. It's 100 count, so that at two a week is a cheap enough.
>

Yes the stuff is cheap, but I think it is a complete waste of time and
may do more harm than good. B12 acts as a methyl donor. It can't
do that without a methyl group. You have to steal a methyl group from
somewhere else to get it active. When you do that you release the
cyanide.

However, I really don't think you have too much to worry about, since
it is unlikely to ever release the cyanide. Cyanocobalamin is a very
stable compound which likely just passes through, getting excreted
in your urine. Cobalamine is excreted in the bile and goes back into the
gut where is re-absorbed. So, you keep using it over and over again.
That is why your body is supposed to have a thirty year supply.

However, I know the 5-10 grams, that my body is supposed to store,
is all gone. I can tell, because when I take a couple methyl-cobalamin
pills I become very calm. This would not happen if I had a 30 year
supply of B12. If that were the case, I would be calm all the time.

I take ten B12 pills (10mg total) one at a time, melting them under my
tongue while I drive into work in the morning. It makes an amazing
difference. I no longer get angry and frustrated with braindead drivers.
I just stay very calm and relaxed.

I seem to use the whole 10mg B12 in less than a day, since I can feel
the affects again the next morning. I think I will have to get clear of
psoriasis to start storing some again.

> As to my current trial, one of the things that is different now
> is my continuing use of glucosamine and chondroitin sulfate from
> costco.com.
>
> Never used that combo with vitamin C and IP6 before. Is that it?
>

I finally found some IP6, and so have started adding that to my
supplements. I have dropped the inositol/IP6 mix. I also got some
RNA/DNA supplement, which I have also added. I added some extra
biotin too, since a deficiency causes dry skin, and dermatitis. I also added
phosphadityl-choline, and am drinking some whey protein shakes.

--------------------------------------------------------------------
http://www.healthtouch.com/bin/EContent_HT/altCareMedShowLfts.asp?fname=00344&title=PHOSPHATIDYLCHOLINE+&cid=HTALT

PHOSPHATIDYLCHOLINE

What is it? Phosphatidylcholine is found in soy lecithin. It can be taken as
dietary lecithin or as a supplement for high cholesterol, atherosclerosis
(fat deposits on arteries), high blood pressure, liver problems, bipolar
depression, dementia, dyskinesias (difficulty making movements), gallbladder
disease, headache, and multiple sclerosis. It is used on the skin for acne
and psoriasis.

http://www.lef.org/magazine/mag98/may98_ginphos.html

A choline deficiency can also be associated with high cholesterol levels,
some types of cardiac symptoms, skin problems such as psoriasis, poor
tolerance of dietary fats, gastric ulcers, high blood pressure, gall stones,
and liver disease.

--------------------------------------------------------------------

I guess I should try rubbing some on P lesions and under my nails.

Have you quit using the NAC? You suggested that I keep it in the
mix. I added it back in.

The NAC acts as a methyl donor and a sulfur donor.

-----------------------------------------------------------------
http://www.lef.org/newshop/items/item00215.html

L-cysteine is a conditionally essential amino acid, one of only three
sulfur-containing amino acids, the others being taurine (which can be
produced from L-cysteine) and L-methionine from which L-cysteine can be
produced in the body by a multi-step process. Cysteine plays a role in the
sulfation cycle, acting as a sulfur donor in phase II detoxification and as
a methyl donor in the conversion of homocysteine to methionine. Cysteine
also helps synthesize glutathione, one of the body's most important natural
detoxifiers. N-acetyl-cysteine is the acetylated form of L-cysteine, which
is more efficiently absorbed and used.54-64
Glutathione (gamma-L-glutamyl-L-cysteinyl-glycine) is a peptide (short
protein)-like molecule synthesized in the body from the three amino acids
L-glutamic acid, L-cysteine, and glycine. Glutathione is one of the body's
most important and powerful antioxidants, helping to detoxify xenobiotics. A
major function of vitamin C is to keep glutathione in its reduced form so
that they can continue to provide free radical quenching effects.

-----------------------------------------------------------------

The IP6 may be reactivating ADP to ATP.

ATP + methyl + homocysteine = SAMe

-----------------------------------------------------------------

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8633060&dopt=Abstract

Purified inositol hexakisphosphate kinase is an ATP synthase:
diphosphoinositol pentakisphosphate as a high-energy phosphate donor.

Voglmaier SM, Bembenek ME, Kaplin AI, Dorman G, Olszewski JD, Prestwich GD,
Snyder SH.

Department of Neuroscience, Johns Hopkins University School of Medicine,
Baltimore, MD 21205, USA.

Diphosphoinositol pentakisphosphate (PP-IP5) and bis(diphospho)inositol
tetrakisphosphate (bis-PP-IP4) are recently identified inositol phosphates
that possess pyrophosphate bonds. We have purified an inositol
hexakisphosphate (IP6) kinase from rat brain supernatants. The pure protein,
a monomer of 54 kDa, displays high affinity (Km = 0.7 microM) and
selectivity for inositol hexakisphosphate as substrate. It can be
dissociated from bis(diphospho)inositol tetrakisphosphate synthetic
activity. The purified enzyme transfers a phosphate from PP-IP5 to ADP to
form ATP. This ATP synthase activity indicates the high phosphate group
transfer potential of PP-IP5 and may represent a physiological role for
PP-IP5.

PMID: 8633060 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------

Cruiser

randall

unread,

Oct 6, 2005, 12:48:58 PM10/6/05

Cruiser wrote:

<sniP>

> > > You seem to be having very good success.

What is remarkable is i'm eating exactly what *seemed* to flare
me for the last 40 years. Taken that i still avoid omega-6 soy
bean/vegetable oils etc. So while i still take a half tablespoon of
flax (3:1 ratio of n3:n6's) and have been also taking ascorbyl
palmitate with NAC and alpha-lipoic acid, these didn't anything prior
to adding in the IP6.

And for previous IP6 trials, i used it mainly in the winter when it
seemed
to do the most good for a month or two.

The extra synergy i'm getting from it now has to be due to the vitamin
C.

I can back out the ip6 or the C and see what happens i suppose.

Certainly my previous trials has shown the ip6 isn't a stand alone
supplement.

And if the C is piggybacking the clearings, i'm not sure i want to
see my skin go south again so soon.

I've been speculating on adding in ala + alc, alcar. Being over 50
the good old dna is certainly going south with or without psoriasis.

In the past the p skin may have been compensatory for how smooth and
supple
my regular skin looked. Thank god that the majority of the time the
good
skin hung out and the bad skin was hidden for the most part.

Just yesterday i was in the grocery store in shorts and sandals without
socks. While i don't have the greatest toe nails, i was happy anyway.

> > >
> >
> > YeP! So keep your fingers crossed. I'm at the end of this trial so i'm
> > contemplating the next modifications.
> >
> > I did pick up the trader joe's B-12. It is the cyano form. Oh well. I
> > did
> > check pubmed and couldn't find your complaints against it. So, till
> > the next bottle, which may be a year, i'll play around with the stuff
> > I've got. It's 100 count, so that at two a week is a cheap enough.
> >
>
> Yes the stuff is cheap, but I think it is a complete waste of time and
> may do more harm than good. B12 acts as a methyl donor. It can't
> do that without a methyl group. You have to steal a methyl group from
> somewhere else to get it active. When you do that you release the
> cyanide.

So? It says right on the methylcobalamin that you avoid two steps
in converting the cyano form.

Big deal. What's the methyl stores from all other sources in the body?

Certainly must be great enough for the average load of b-12? I may
as well break these little pills in two? As most doesn't absorb anyway.

How many steps does the body go thru to gain a little energy,
http://www.columbia.edu/cu/biology/courses/c2005/handouts/krebs.9.h.gif

And how dependent is psoriasis on either process?

Is it sapping the energy or are the cortisol levels more at cause of
that?

>
> However, I really don't think you have too much to worry about, since
> it is unlikely to ever release the cyanide. Cyanocobalamin is a very
> stable compound which likely just passes through, getting excreted
> in your urine.

So? Your saying it's worthless? Read the abstracts on pubmed.

I can find hundreds of them that say tested values go up with
cyanocobalamin supplementation. I'll take my chances.

In younger headier days i trusted other compounds with LOCKED up
arsenic and what have you.

> Cobalamine is excreted in the bile and goes back into the
> gut where is re-absorbed. So, you keep using it over and over again.
> That is why your body is supposed to have a thirty year supply.
>

Then is my gut p link suppose to be linked to intrinsic factor in
your speculations?

> However, I know the 5-10 grams, that my body is supposed to store,
> is all gone. I can tell, because when I take a couple methyl-cobalamin
> pills I become very calm. This would not happen if I had a 30 year
> supply of B12. If that were the case, I would be calm all the time.
>

And then you eat the carrots and you do the tom cruise dance routine
from home alone? <G>

> I take ten B12 pills (10mg total) one at a time, melting them under my
> tongue while I drive into work in the morning. It makes an amazing
> difference. I no longer get angry and frustrated with braindead drivers.
> I just stay very calm and relaxed.
>

Are you sure your not taking a toke along the way? lol
Try taking a deep breath and let it out slowly. Shall i find
a O2, CO2 conversion chart, that factors in brain waves?

What is it? The alpha waves? Are meditative?

> I seem to use the whole 10mg B12 in less than a day, since I can feel
> the affects again the next morning. I think I will have to get clear of
> psoriasis to start storing some again.

Could your thyroid need checking? Know more then a few psoriatics that
have had low numbers there.

>
> > As to my current trial, one of the things that is different now
> > is my continuing use of glucosamine and chondroitin sulfate from
> > costco.com.
> >
> > Never used that combo with vitamin C and IP6 before. Is that it?
> >
>
> I finally found some IP6, and so have started adding that to my
> supplements.

OK. For how long and what's been the effects?

<sniP>

Well, ran outa time.

Something in relationshiP to IP6 is causing my P to succumb to the
theta waves.

Thats it! They've become hyPnotized, fell asleeP and woke up nice
CLEAR and refreshed as regular skin?

randall... now i'm dreaming!
------------------------------------------------------
>
> Cruiser

Cruiser

unread,

Oct 6, 2005, 1:47:34 PM10/6/05

"randall" <ranh...@aol.com> wrote in message

news:1128617338.1...@g47g2000cwa.googlegroups.com...

>
> > I finally found some IP6, and so have started adding that to my
> > supplements.
>
> OK. For how long and what's been the effects?
>

I just started on a pure IP6 supplement yesterday.

I was taking IP6 and inositol mixed together, but the container did not
specify how much was IP6. It was all that I could find at the time.

I stopped with the ascorbic acid last week. I am now drinking orange juice
and eating navel oranges. I want the real natural folic acid in the oranges.
I am getting plenty of Vitamin C, because I find I have to be very careful
how much orange I drink and eat, to avoid diarrhea.

There was no overnight pure-IP6 and vitamin C miracle.

How long before you saw any benefit?

I am going to try some of the phosphadityl-choline topically on my lesions
tonight, to see if that helps at all.

Cruiser

randall

unread,

Oct 6, 2005, 3:52:35 PM10/6/05

Cruiser wrote:
> "randall" <ranh...@aol.com> wrote in message
> news:1128617338.1...@g47g2000cwa.googlegroups.com...

> How long before you saw any benefit?
>

Saw it start the next day and it just increased daily. Only till i
went hog wild eating pork and increasing permeability in the gut with
white wine did i see a reversal. Without the ip6 that repast would
have flared me to at least 30% in very short order.

Red wine as well would drive those levels up, but hardly a dent while
on the ip6! Would you say it was/is the resveratrol or boron in the
grape skins? <g>

Yet with the on going thewholewhey.com proflora shakes, i'm somewhat
more
bullet proof in the gut.

So, while in the past this type of diet would have me plaqued out
quickly,
it now takes considerable more cheat eating to get there.

And with awarness, it's like watching slow motion in a less negative
direction.

Provided i'm doing the iP6.

Even now as i watch the benefits diminish due to the LPS leaking? I
wonder
how much it's a foe as oPPosed to an ally?

Yep, said it. My theory is looking at a metamorphosis.

The radical randall gut theory goes turbo! Back to you.

Now that i'm thinking about your b12 mega-dosages, i can only
wonder as to HPA effects?
http://groups.google.com/groups?q=hpa+psoriasis&qt_s=Search

Are your adrenals on a teeter totter?

Take a big toke of fresh air and let it out slowly now.

Is P a CO2 thing then?

> I am going to try some of the phosphadityl-choline topically on my lesions
> tonight, to see if that helps at all.
>

I see it in the groups,

http://groups.google.com/groups?q=phosphatidyl-choline+topical&

But more so on the web,
http://www.google.com/search?q=phosphatidyl-choline%20topical&sa=N&tab=gw

Yet why bother? You'll only confuse the results of your IP6 trials.

Then you'll face a greater dilemma as to what's doing what.

randall... & i know what cheat eating leads to!

> Cruiser

cruiser

unread,

Oct 6, 2005, 11:02:10 PM10/6/05

"randall" <ranh...@aol.com> wrote in message

news:1128628355.9...@f14g2000cwb.googlegroups.com...

>
> Now that i'm thinking about your b12 mega-dosages, i can only
> wonder as to HPA effects?
> http://groups.google.com/groups?q=hpa+psoriasis&qt_s=Search
>

The body can't make its own cobalamin. It re-uses it, if it is not attached
to a cyanide.
The 5-10 grams that your body can store, can last 30 years, but exercise,
infections, toxins, alcohol, smoking, stress, etc. deplete your supply. The
tank runs dry. Taking large amounts is intended to satisfy current needs and
try to store a bit for a rainy day. It would take 500 days of taking B12 at
my current levels to restore 5 grams. 1000 Days would be needed to store 10
grams. Those figures are not considering the ongoing depletion due to
chronic inflammation, and other insults to my body. I figure that with
current usage, I am not likely storing very much at all, if any. That is why
I figure that I have to get clear of psoriasis to put some in the bank.
Either that or I am going to have to go to the doctor and request a series
of high dose B12 shots.

That homocysteine is nasty stuff. I don't like the idea that it makes me
edgy and irritable.

Cruiser

unread,

Oct 7, 2005, 9:51:31 AM10/7/05

Just found this:

http://64.224.202.237/supplementinfo.htm
Caution: Even additional B12 may not protect against Bi2 deficiency when one
takes megadoses of Vitamin C.

Cruiser

unread,

Oct 7, 2005, 10:00:56 AM10/7/05

>As to my current trial, one of the things that is different now
>is my continuing use of glucosamine and chondroitin sulfate from
>costco.com.

http://www.albertdavidindia.com/products/arthiritis/arthiritis.htm

Chondroitin, like glucosamine, also increases RNA synthesis by chondrocytes,
which enhances the production of proteoglycans and collagen. Chondroitin
also prevents cartilage damage by blocking activity of elastase and
hyaluronidase.

Cruiser

unread,

Oct 7, 2005, 11:33:13 AM10/7/05

I seem to be finding quite a few interesting things today.

Here is something very interesting that I just found.

------------------------------------------------------
http://www.ironlife.com/mag/issue16/anabolic.shtml

Cortisol is the most feared hormone for bodybuilders. It's a powerful
catabolic stress hormone that among other actions cannibalizes muscle
tissue. The worst effects most people don't know, like the breakdown of
connective tissues, lowered immunity, reduced muscle RNA synthesis and above
all else accelerate the aging process. Makes you kind of wonder why in the
Hell the body would produce such a thing well, when the body is stressed it
triggers the fight or flight mechanism, which will shoot cortisol threw the
roof. The hormone mobilizes the body for action for emergency fuel and
reduce swelling in the event of a possible injury. When we train hard
causing trauma to muscle the body believes its in danger and will release
cortisol.

High cortisol levels will impair entry of amino acids into muscle cells.
Injectable testosterone will over take this hormone and increased the
anabolic state but, your not stopping cortisol your just increasing the
anabolic end over the catabolic state. To the hard training bber looking to
get massive a post workout slin shot of at least 10 ius will further
increase the anabolic state and nock cortisol on its ass but, what about the
rest of the time we cant just go around doing slin all day can we.

Well there is a supplement that can block cortisol and I have no idea why it
hasn't caught on. There was plenty of research going on about it in the 80s
that was very promising it was even given to patients after surgery its
phosphatidylserine or PS for short don't believe me type it in a search on
yahoo or what ever and you will get a ton of links. PS is a natural
occurring pholipid found in cell membranes. PS in the body is highest in the
teenage years. I have read studies that show when giving PS to older adults
it will improve memory, sharpen attention and even reduce depression. I
believe a cortisol increase after a cycle is over to be key in some peoples
depression when coming off.

PS seems to inhibit the hypothalamus pituitary adrenal axis response to
stress which in turn means less cortisol release after a workout. When I
searched for studies on the net I found one that was very surprising it was
from a Dr in Italy that in 1992 gave oral PS to 10 bike riders another 10
received a placebo after 1hr of cycling cortisol levels was tested in the
blood they found the group taking PS had 30% less cortisol than the placebo
group.

Here is an overview of what PS will do and some studies you can checkout
yourself :

Phosphatidylserine prevents the decline in Learning capacity that occurs
with age.
Phosphatidylserine prevents the decline in the number of brain dendrites
that occurs with age.
Phosphatidylserine improves Mood (especially in elderly persons.)
Phosphatidylserine is involved in Myelin Sheath repair.
Phosphatidylserine increases the number of neurotransmitter receptor sites.
Phosphatidylserine stimulates release of the brain neurotransmitter
Dopamine.
Phosphatidylserine improves Reflexes [as judged by flicker-fusion response
time.
Phosphatidylserine counteracts Cortisol that rises during intensive exercise
and during stress.
Phosphatidylserine enhances the function of Nerve Growth Factor (NGF).
Phosphatidylserine increases production of the brain neurotransmitter
acetylcholine.
Phosphatidylserine enhances brain glucose metabolism.

Is this a wonder drug no but it is very useful the main dosage is 100mg
given 3x a day. I have found it really comes down to bodyweight and the
amount of stress placed on the body 500-800mg before a workout works well to
suppress cortisol and when coming off cycle 200-300mg given 2x a day is what
I take for 4 weeks. It might not work for everyone but please give it a try
just for the depression benefit alone its worth it. Off cycle depression is
just the worst and, it seems this is a forgotten product. If you decide to
give it a try please stop by ironlife and post your thoughts in the
bodybuilding forum I would love to hear from you.

------------------------------------------------------------

I picked some up today to add to my supplements, along with some glucosamine
and chondroitin sulfate.

Cruiser

randall

unread,

Oct 11, 2005, 3:51:33 PM10/11/05

Cruiser wrote:
> I seem to be finding quite a few interesting things today.
>
> Here is something very interesting that I just found.
>
> ------------------------------------------------------
> http://www.ironlife.com/mag/issue16/anabolic.shtml

Is the P iron life caused by this?
http://english.osu.edu/programs/undergraduate/images/HenryVIII's%20armor%20in%20the%20Tower.jpg

Or is all that iron in the skin?

Nice codpiece. lol

I wonder if the swords got smaller as a result of the umcomfortable..

Never mind. lol

A review of swords and armor may be in order.

Seems i can't get off of this one. hehe

>
> Cortisol is the most feared hormone for bodybuilders. It's a powerful
> catabolic stress hormone that among other actions cannibalizes muscle
> tissue.

Bingo! Now cocktail that with HPA-axis and P. If your adrenals are shot
and i know yours aren't, your gonna feel depressed. We do know that
sPeed kills. You can turbo charge the body only so long before the
weak links begin to break. Look at body armor now as opposed to then.

The old time stuff while practical for then would make you a sitting
target now. We need to normaize adrenal function, not put a codpiece
over it.

> The worst effects most people don't know, like the breakdown of
> connective tissues, lowered immunity, reduced muscle RNA synthesis and above
> all else accelerate the aging process.

Yet, we have young skin in those non-involved areas. Which brings
up another un-clear area to look in to.

> Makes you kind of wonder why in the
> Hell the body would produce such a thing well, when the body is stressed it
> triggers the fight or flight mechanism, which will shoot cortisol threw the
> roof. The hormone mobilizes the body for action for emergency fuel and
> reduce swelling in the event of a possible injury. When we train hard
> causing trauma to muscle the body believes its in danger and will release
> cortisol.
>

Sounds like a time to understand the gut brain.

Hey BABY, how's your mom?
http://news.bbc.co.uk/1/hi/health/4286512.stm

Those scientologists have an answer,
http://news.scotsman.com/latest.cfm?id=2068132005
Good luck tom and katie. But wasn't she suPPose to stay chaste
till wed?

Now add this one to it,
http://www.signonsandiego.com/uniontrib/20051005/news_1c05brain.html

Then add in my gut feelings.

Is P somewhere in this gutter? lol

Could we have a gut brain iron permeable gut LPS gene thing?

I need to rePhrase that last inquiry. <g>

Does our uPstair brain screw with the gut brain and make more p?

> High cortisol levels will impair entry of amino acids into muscle cells.

So thats why i had such a hard time bulking up for high school
football?

Darn, i may have used roids if they had been around back then.

On second thought good thing they weren't. I'm not so sure that P and
roid rage go to-gether any better then P and anything.

<sniP>

So now its been nearly a week of PS. With all that B12 you must be
going
thru teenage roid rage about now. lol

Sorry. Couldn't resist once again.

randall my gut feelings are still there. Butterflies or 2 much
thinking?
>
> Cruiser

Cruiser

unread,

Oct 12, 2005, 9:17:38 AM10/12/05

"randall" <ranh...@aol.com> wrote in message

news:1129060293.5...@g44g2000cwa.googlegroups.com...

> Bingo! Now cocktail that with HPA-axis and P. If your adrenals are shot
> and i know yours aren't, your gonna feel depressed.

Actually, I haved been feeling depressed, and drained. I have been
running on empty for awhile. I've gotten tired of the parties and have
felt run down. I have not been kayaking or mountain biking as much
this summer. I have been leaving parties early instead of being one of
the last to go.

>
> > The worst effects most people don't know, like the breakdown of
> > connective tissues, lowered immunity, reduced muscle RNA synthesis and
above
> > all else accelerate the aging process.
>
> Yet, we have young skin in those non-involved areas. Which brings
> up another un-clear area to look in to.
>

You have young skin? I have rosesea on my cheeks, and wrinkles. I have
gray hair at the temples and over the ears. People tell me that I look much
younger than I am, but I am still showing the signs of aging.

>
> So now its been nearly a week of PS. With all that B12 you must be
> going thru teenage roid rage about now. lol
>

Acutally, I am much more calm.

The interesting thing is that PS is supposed to keep the immune system from
attacking apoptotic cells until they are gone. It reduces inflammation.

I am not certain that PS blocks cortisol from entering the blood stream, or
if it just blocks cortisol from getting at the apoptotic cells.

If it does block cortisol for entering the blood stream, it will also allow
the
T-cells to come out and play. Apparently, cortisol makes the T-cells all run
and hide in bones, until cortisol levels drop, and then they return to the
bloodstream. Guess what happens if cortisol doesn't drop, because of
constant endless stress and inflammation.

Cruiser

randall

unread,

Oct 12, 2005, 12:13:02 PM10/12/05

Cruiser wrote:
> "randall" <ranh...@aol.com> wrote in message
> news:1129060293.5...@g44g2000cwa.googlegroups.com...
>
> > Bingo! Now cocktail that with HPA-axis and P. If your adrenals are shot
> > and i know yours aren't, your gonna feel depressed.
>

> Actually, I have been feeling depressed, and drained. I have been

> running on empty for awhile. I've gotten tired of the parties and have
> felt run down. I have not been kayaking or mountain biking as much
> this summer. I have been leaving parties early instead of being one of
> the last to go.
>

Bummer!

You can park on the couch and eat jello. <g>

Yet, we may good usage for your little grey cells.

> >
> > > The worst effects most people don't know, like the breakdown of
> > > connective tissues, lowered immunity, reduced muscle RNA synthesis and
> above
> > > all else accelerate the aging process.
> >
> > Yet, we have young skin in those non-involved areas. Which brings
> > up another un-clear area to look in to.
> >
>
> You have young skin? I have rosesea on my cheeks, and wrinkles. I have
> gray hair at the temples and over the ears. People tell me that I look much
> younger than I am, but I am still showing the signs of aging.
>

At some point we all age. Even Dick Clark. Sure he looked great, but
strokes
don't care what you look like. I look at my dad and figure i'm looking
at a forward time machine. And my kids look better then I or is that
due to memory lapse?

Hell, if it wasn't for the P, i remember looking better then them. lol

See! P must have some benefit hidden from view.

> >
> > So now its been nearly a week of PS. With all that B12 you must be
> > going thru teenage roid rage about now. lol
> >
>
> Acutally, I am much more calm.
>

Good then you won't need to burn the mid night oil.
I sat around and watched this einstein show on PBS last night. It
was cool. Did you know that matter is just condensed energy?
Yeah and pack enough stuff into a neutron star and smack then to-gether
and you can make gamma wave bursts that rival any old big bang for
that split second or so. I liked to see you party thru that event. lol

Oh wait. I guess we all did and 12-14 billion years later we're still
looking for the light.

And some of us want to send our P into the light right now.

> The interesting thing is that PS is supposed to keep the immune system from
> attacking apoptotic cells until they are gone. It reduces inflammation.
>

I've used it over the years. Maybe i'll bring it back in for the IL-10
stimulation. We know that helps to lower The TH1 cells and that can't
hurt. But first I want to observe the effects of doubling the IP6.

> I am not certain that PS blocks cortisol from entering the blood stream, or
> if it just blocks cortisol from getting at the apoptotic cells.

I forget as well,
http://www.signonsandiego.com/news/health/20050620-2317-folicacid-brain.html

>
> If it does block cortisol for entering the blood stream, it will also allow
> the
> T-cells to come out and play. Apparently, cortisol makes the T-cells all run
> and hide in bones, until cortisol levels drop, and then they return to the
> bloodstream. Guess what happens if cortisol doesn't drop, because of
> constant endless stress and inflammation.

Don't have to guess. My adrenals tiP at the droP of a hat.

How is your rna thing going?

How much B-9 (folate) did you say you were getting?
http://www.signonsandiego.com/uniontrib/20051012/news_lz1c12folate.html
(read down to the Alzheimer's section for maximum dosage ~740mcg's for
64 + year olds?)

As to my trials, i've been eating pork every day and still clearing due
to the one gram a day of IP6. I do have some itchyness thats begining
to
bug me. The itching seems to be mainly on my scalP.

When i was little, i recall now my dad scratching his scalp. I thought
he
wanted to hit me. lol

randall... the fear of god is better then the itch of P, got B's?
>
> Cruiser

randall

unread,

Oct 12, 2005, 12:53:54 PM10/12/05

Hi,

P news from around the world. UK today,

http://www.responsesource.com/releases/rel_display.php?relid=22909&hilite=

New report highlights inadequacies in psoriasis care

* Submitter: Athena Medical PR [View Response Source PR Company
Listings]
* Release Date: 12-10-2005
* 4 views on Response Source
* Use Response Source to send requests to all PR contacts.

October 12, 2005. A new report highlighting the plight of the 1.2
million people in the UK with psoriasis has led to calls from leading
dermatology experts and patient groups for improved standards of care
and support for people living with the condition.

Launched at the European Academy of Dermatology and Venereology (EADV)
14th Annual Congress, taking place in London on October 12-15, 2005, a
panel of the UK's leading dermatologists and patient groups, including
the Psoriasis Association and the Skin Care Campaign, has joined forces
to author the Making Psoriasis a Priority report.

With research showing that 37% of those with psoriasis have been
shunned, taunted or abused, a key recommendation of the report is to
improve public awareness of the disease to dispel stigmas and
mistruths.

Gladys Edwards, Chief Executive of the Psoriasis Association commented:
"Although psoriasis is not contagious, many people know very little
about this common skin disorder. Such strong and negative reactions
experienced by those with psoriasis just emphasize the need for a
greater understanding of the impact that coping with a chronic skin
condition can have on a person's life."

This was reiterated by Dr Anthony Bewley, Consultant Dermatologist,
Whipps Cross University Hospital, Barts and the London NHS Trust, who
said that not only are psoriasis patients still banned from some
swimming pools, but many are also prevented from trying on new clothes
by uninformed shop assistants.

The report also highlights the low priority given to psoriasis and
dermatology disorders by the NHS, and identifies a lack of
understanding among many healthcare professionals. Professor
Christopher Griffiths, Professor of Dermatology at Hope Hospital,
University of Manchester said: "Skin diseases are rarely
life-threatening, so there is a tendency for healthcare professionals
to underestimate the impact that they can have on patients' social and
working lives. Making Psoriasis a Priority highlights the psychological
impact of psoriasis and as GPs spend up to 20% of their time treating
skin disorders, this is an area that cannot be ignored.

"GP dermatology training currently consists of only around two weeks,
so at the moment many GPs aren't confident in treating conditions such
as psoriasis. Because of the low priority given to psoriasis we are
sometimes seeing inappropriate treatment."

According to Prof Griffiths, some patients are also unnecessarily
referred to hospital specialists, when they could often be treated by
GPs. These factors contribute to prolonged waiting lists and can delay
access to effective treatment.

Psoriasis impairs quality of life to the same degree as diabetes, heart
disease and some cancers. The report recommends a concerted move to put
skin diseases such as psoriasis on the Department of Health's agenda
for chronic disease management, and to increase funding for healthcare
professional training.

"Psoriasis patients are at twice the risk of committing suicide than
the rest of the population," added Dr Bewley, who focuses on the
psychological effect of the disease.

Sponsorship of the report was provided by LEO Pharma and developed in
conjunction with The Psoriasis Association and the Skin Care Campaign.
A copy of the report can be obtained from Joanna Smith at LEO Pharma on
01844 276 286.

- ENDS -

Further information:

For further information, or to arrange an interview with Gladys
Edwards, Chief Executive of The Psoriasis Association or Dr Anthony
Bewley, Consultant Dermatologist at Whipps Cross Hospital, please
contact Athena Medical PR:

Raine Marcus
Tel: 020 8956 2286
Ra...@athenamedicalpr.com

Lucy Howell
Tel: 020 8956 2298
Lu...@athenamedicalpr.com

For further information on psoriasis please contact:

The Psoriasis Association
Milton House
7 Milton Street
Northampton
NN2 7JG
Tel: 0845 676 0076
Fax: 01604 792894
Website: www.psoriasis-association.org.uk

Notes to editors
. About Psoriasis
o Psoriasis is a very common non-contagious skin disorder, affecting
approximately 1.2 million people in the UK.
o Psoriasis is an inflammatory skin condition that can occur at any
age.
o The disease is not infectious, nor can it be transferred from one
part of the body to another.
o Chronic plaque psoriasis is the most common form and it is
characterised by raised red plaques which are often painful, itchy and
unsightly.
o The exact cause of psoriasis is unknown although more is known today
compared with a decade ago. It is thought that genes play a part in the
disease and that 1 in 3 people with psoriasis has a close relative who
also suffers from it.
o Certain factors may trigger a psoriasis flare up, which include:
smoking, alcohol, stress and climatic changes.
o Psoriasis varies in its severity and duration. Some cases are mild,
while others are disfiguring and debilitating, and can lead to
considerable distress and diminished quality of life.
o Drug treatments include:
? Ointments, creams and lotions known as local or topical therapy
? Topical treatments, such as vitamin D analogues, coal tar and topical
corticosteroids that work directly on the condition
? Systemic therapy for more severe psoriasis such as biologics,
treatments that are designed to alter an immune response, which can be
used with or without light or photo therapy.

*******************^^^^^^^^^^^^^^^^****************^^^^^^^^^^^^^^^^^^

randall... don't they have FAEs in the UK?

Cruiser

unread,

Oct 12, 2005, 2:40:21 PM10/12/05

"randall" <ranh...@aol.com> wrote in message

news:1129133582.7...@f14g2000cwb.googlegroups.com...

>
> Cruiser wrote:
> > "randall" <ranh...@aol.com> wrote in message
> > news:1129060293.5...@g44g2000cwa.googlegroups.com...
> >
> > > Bingo! Now cocktail that with HPA-axis and P. If your adrenals are
shot
> > > and i know yours aren't, your gonna feel depressed.
> >
> > Actually, I have been feeling depressed, and drained. I have been
> > running on empty for awhile. I've gotten tired of the parties and have
> > felt run down. I have not been kayaking or mountain biking as much
> > this summer. I have been leaving parties early instead of being one of
> > the last to go.
> >
>
> Bummer!
>
> You can park on the couch and eat jello. <g>
>

I am not that bad yet. Instead, I sit in front of the computer and do
endless searches for clues about a cure.

>
> How is your rna thing going?
>

Things are looking very interesting at the moment. I will report when I have
something very clear and definite to report. I don't want to consider what
could be transient trends. No lesions have completely cleared so far.

I changed some things in the last couple days. I added glutathione reduced
back into the mix big time 1g/day (20 X 50mg), and I added a 300mg magnesium
supplement. I also reduced many of the things I am taking. I was taking like
6-8 x 800mg IP6 a day for a couple days, but I scaled that back to 2 x
800mg, for the past couple days.

I don't know if the feasting on the weekend helped, or if the changes are
helping, but things appear better over the last couple days.

> How much B-9 (folate) did you say you were getting?

4.8 mg per day of supplement, plus two or three big glasses of orange juice.

Cruiser

randall

unread,

Oct 16, 2005, 12:52:37 AM10/16/05

Hi,

P news from around the world.

Lps came uP again in my last few posts. So I went looking once again.

LPS and Aging,
http://www.sciencedaily.com/releases/2005/10/051012084728.htm

Finally, someone is looking closer at the inflammations of life!

And someone is looking at fat in the gut,
http://www.sciencedaily.com/releases/2005/10/051011074219.htm

Eating -- particularly eating fat-rich foods -- causes cells in the
small
intestine to produce a hormone called cholecystokinin, or CCK. CCK
stimulates digestion and gut peristalsis (the motion that propels food
along
the digestive tract), and also triggers satiation -- the full feeling
that
prompts you to stop eating.

The study by Luyer and colleagues shows that fat-induced CCK can also
dampen
inflammation in the gut, as rats fed a high-fat diet were protected
against
lethal bacteria-induced shock whereas those fed a low-fat diet were
not. CCK
sent signals to the brain through the vagus nerve, the nerve that
provides
the electrical regulation for many internal organs, including the gut
and
the heart. In response to CCK, vagus nerve endings in the gut released
a
neurotransmitter called acetylcholine. Acetylcholine then bound to
proteins
on immune cells and turned the cells off.
The authors think this pathway might explain why the immune system
doesn't
react to food proteins and normal gut bacteria as if they were foreign
invaders. <sniP>

****************

What you eat does affect you, (how much is the question)
http://groups.google.com/group/sci.life-extension/browse_frm/thread/08a81c101f2a8090/42b7906a97d366dc#42b7906a97d366dc

***********

Got flaky skin? Got really dark skin?
We've got a cream for you!
http://observer.guardian.co.uk/uk_news/story/0,6903,1593303,00.html
(...)
the scale of the problem is alarming.
<sniP>

Tragic yes that flaky white and really dark skinned folks will go to
such lengths
for peace of mind. And the pharma's to stay in biz will exploit the
insured.

Whoops, headed for a rant. StoP that. Ok.

*****************

Drug company, Immune ResPonse went from $160 share to .37 cents.
http://www.nctimes.com/articles/2005/10/16/business/news/15_58_1310_15_05.txt

***********

Not even Jonas Salks company is immune from the business world?

randall... haven't tried the glucaric acid or located it! Maybe
tomorrow!

randall

unread,

Oct 20, 2005, 1:03:00 PM10/20/05

Hi,

Our first link today brings up age old P questions.

Remicade fixes the gut for UC folks. Does that mean less lPS leakage
for psoriasis folks as well? Or does blocking TNF simply close the
loose junctions in the gut?

Are the mucosal tissues in the gut the front line for curing P?

Hey! Fixing my guts (wit kit/proflora whey) seemed to point in that
direction.

And when i do my trials now, i use alcohol to determine efficacy.
As it works so quickly to re-ignite the fires of P.

http://www.cnw.ca/fr/releases/archive/October2005/19/c2947.html
REMICADE(R) Achieves Long-Term Treatment Goals of Mucosal Healing and
Remission in Patients with Ulcerative Colitis

Data Presented at UEGW Meeting Also Demonstrate Reduction in
Hospitalizations
and Improved Quality of Life

COPENHAGEN, Denmark, Oct. 19 /CNW/ -- A pooled analysis from two
landmark clinical trials in patients with active ulcerative colitis
(UC) shows
a majority achieved mucosal healing soon after treatment with
REMICADE(R)
(infliximab), with positive results maintained over time.

<sniP>

**************

While i agree with manfreds assessment on uwe and nac,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_frm/thread/957a9357fff1c49b/edbd288651761ee6#edbd288651761ee6

I'm able to make positive connections to my current trial with his
continual examination of the subject. Could my ~6 grams of vitamin C
be the magic with the NAC i'm taking? As to that i'm experimenting with
half a gram to one gram a day every other day for the last few days.

Being that i'm not willing to stop the half gram of iP6 or the nac,
unless
i forget to take it, i guess i'm hooked on clear. :(

Being clear has screwed uP my objectivity. Sorry folks!

I am trying to keep my eye on the targets i deem imPortant.

Vanadyl Sulphate helps recovery from LPS,

http://www.betterhumans.com/News/4722/Default.aspx
&
http://www.innovations-report.de/html/berichte/medizin_gesundheit/bericht-50271.html

So, it indirectly proves lPS leakage should you take 10-20 mcg's and
clear a little? And VS helps with wound healing and growth in youth.
But what the heck, alcohol and spices that cause gut leakage in the
colon allow for LPS to leak. Should that be in your P pathway.

How much VS is in breastmilk? <g>

**************

Moving on to another curious and far deadlier immune condition.

While sarcoidosis is rarer then P and more prevalent amongst
those that don't get P, it is worth looking at.

Why? You tell me.

After reading this link.

http://www.dunnconnect.com/articles/2005/10/17/health/health01.txt
THOUSAND OAKS, CALIF. - The Autoimmunity Research Foundation announced
at the beginning of this month that its Phase 2 clinical trials had
confirmed antibiotic-resistant bacteria as the cause of sarcoidosis,
the deadly disease that took Reggie White's life, and that applications
for designation of three antibacterials as "Orphan Products" have been
filed with the Food and Drug Administration.

The foundation has been conducting Phase 2 trials for the past three
years, working with dozens of individual physicians and specialists to
establish both an understanding of the pathogenesis, and of effective
anti-bacterial dosing regimes. More than 200 of its patients have
subsequently recovered, or are currently recovering, from this
debilitating disease.

The applications to the FDA will facilitate Phase 3 trials leading to
final FDA designation of these drugs for sarcoidosis.

Trevor G. Marshall, Ph.D, a foundation director, has discovered and
published exactly how slow-growing, intra-phagocytic bacteria can cause
chronic disease. The antibiotics needed for recovery are neither
expensive nor new, but Dr. Marshall and his colleagues have developed a
method of using them which is both new and revolutionary.

In March 2005, the foundation held an international conference where
physicians and patients attended sessions focused on understanding this
deadly disease. Experts described how tiny intra-phagocytic bacteria -
called L-forms, after the Lister Institute, where they were discovered
- are the cause of sarcoid inflammation.

Patients described what they had experienced as they recovered their
health using the innovative antibiotic regimen.

One single mother described how she had struggled to tell her
13-year-old son that she was dying, and that she would never be able to
leave her wheelchair. Two years later, she is walking again, albeit
with a cane, enjoying being a "soccer mom."

Another patient explained she had been forced to give up competitive
show jumping as sarcoidosis made her weaker, selling her prized horse
as she was confined to a spinal brace and anticipating a wheelchair.
Now she is riding again in competition, with her health steadily
improving.

A word from ARF's Marshall T.G and Marshall F.E,

raises hope for other diseases

"From time to time there have been reports of autoimmune disease
succumbing to tetracycline antibiotics, but many have assumed this was
due to coincidence, or to some ill-defined 'anti-inflammatory property'
of the tetracyclines. But now the inflammation of sarcoidosis has
succumbed to antibiotics in two independent studies.

"This review examines the cell wall deficient (antibiotic resistant)
bacteria which have been found in tissue from patients with
sarcoidosis. It examines how such bacteria can infect the phagocytes of
the immune system, and how they may therefore by responsible for not
only sarcoid; inflammation, but also for other autoimmune disease.
Proof positive of a bacterial pathogenesis for sarcoidosis includes not
only the demonstrated ability of these studies to put the disease into
remission, but also the severity of Jarisch-Herxheimer shock resulting
from endotoxin release as the microbes are killed.

"Studies delineating the hormone responsible for phagocyte
differentiation in the Th1 immune response, 1,25-dihydroxyvitamin D,
are discussed, and its utility as a marker of Th1 immune inflammation
is reviewed.

Finally, data showing that the behavior of this hormone is also
aberrant in rheumatoid arthritis, systemic lupus erythematosus, and
Parkinson's, raise the possibility that these diseases may also have a
CWD bacterial pathogenesis."

More advances

Earlier this month, the Nobel Prize Committee issued a press release
announcing the 2005 Nobel Prize in Medicine; stating, inter alia, "Many
diseases in humans such as Crohn's disease, ulcerative colitis,
rheumatoid arthritis and atherosclerosis are due to chronic
inflammation. The discovery that one of the most common diseases of
mankind, peptic ulcer disease, has a microbial cause, has stimulated
the search for microbes as possible causes of other chronic
inflammatory conditions."

Dr. Barry Marshall was just awarded the Pulitzer Prize for his
discovery that a microbe causes stomach ulcers.

It should be noted that Dr. Trevor Marshall is no relation to Dr. Barry
Marshall, although they are both alumni of the University of Western
Australia and trained in the same QEII Medical Center in Perth, Western
Australia, during the same time period (early '80s).

What is Sarcoidosis?

Sarcoidosis is a chronic inflammatory condition, a rare disease
characterized by inflammatory lumps, or granulomas, that may form in
many organs. It can be either short or long term and can affect any
organ in the body. Eventually, it affects more than one organ. The
lungs are the most commonly affected and chest pain may result. The
granulomas seem to form as an overreaction to an unknown threat.

What is the Cause?

Until recently, the cause of sarcoidosis was unknown, but now it is
known that the cause is antibiotic-resistant bacteria.

There appears to be genetic factors in some patients with the disease
that makes them susceptible to it. Sarcoidosis does run in families.

It may also affect different races, ethnic groups and populations
differently. For example, Japanese people are more likely to be
affected in the heart and eyes, while in Northern Europeans the skin is
affected along with another organ, such as the lungs.

The disease may be related to infections similar to tuberculosis.
Environmental factors, such as exposure to potentially toxic
substances, may increase the risk of developing it.

What are the Symptoms?

Sarcoidosis may have minor symptoms or none at all. Symptoms depend
greatly on what organs are affected and how much they are affected.
General symptoms include fever, fatigue and overall unwell feeling.
Symptoms of sarcoidosis in the lungs include shortness of breath, cough
and chest pain.

How is it Detected?

Sarcoidosis is often first detected by X-ray. A series of other tests,
including a biopsy of affected tissue, confirm diagnosis. The criteria
for diagnosis are detection of the characteristic symptoms and
abnormalities, particularly on a chest X-ray, ruling out infections and
finding sarcoidosis granulomas in biopsy. If other findings are highly
suggestive of sarcoidosis, a biopsy may not be needed.

^^^^^^^^^

What does sarcoidosis look like?

http://www.aafp.org/afp/20020415/1581.html

For those of you who didn't know who Reggie White was,
http://www.reviewjournal.com/lvrj_home/2004/Dec-27-Mon-2004/photos/sports.jpg

http://graphics.jsonline.com/graphics/packer/img/news/dec04/db1226a.jpg

http://groups.google.com/group/alt.obituaries/browse_frm/thread/5c388cc37e81d268/20e1727518f529c3?lnk=st&q=Sarcoidosis&rnum=6#20e1727518f529c3

If you want to take antibiotics till the bugs get the uPPer hand,
we all become victims in the long run.

Could reggie have been helped with vanadyl sulphate or a skin condition
that exfoliates the problems/toxins quicker? Could P be compensatory in
some cases?

???

randall... time to exercise a little restraint.

Cruiser

unread,

Oct 20, 2005, 1:55:41 PM10/20/05

"randall" <ranh...@aol.com> wrote in message

news:1129826399.0...@o13g2000cwo.googlegroups.com...

> i forget to take it, i guess i'm hooked on clear. :(
>
> Being clear has screwed uP my objectivity. Sorry folks!
>

Randall, are you completely clear of P lesions/plaques now?

I do not recall you saying previously that you are completely 100% clear.

You talked about reducing the amount of coverage, but I have not
seen any previous mention of 100% clear.

I have yet to clear anything, well maybe one small spot.

Right now I am working on the Kreb's cycle. There are some interesting
things going on related to riboflavin, boron, and the thyroid that I want to
explore.

I seems that thyroxin is produced by the thyroid and this involves iodine
and manganese. Thyroxin regulates flavokinase, which is needed to make
FAD and FMN from riboflavin. FAD is important in the Krebs Cycle.

http://waltonfeed.com/self/health/vit-min/b2.html

Further, high boron supplementation causes riboflavin deficiency.

This could explain why, when I started Boron at high levels, I developed
some new psoriasis lesions. If so, suggests that low riboflavin in as a
possible cause of new psoriasis lesions.

I have been reading the information on riboflavin and it has some very
interesting propeties, that have me now looking very closely at it.

In particular, I have always been particularly sensitive to bright light.
Unless I wear sunglasses, I find myself squinting on bright sunny days.
I have never understood this. Why am I more sensitive to bright light
than most other people?

-----------------------------------------------------------------------
http://www.emedicine.com/med/topic2031.htm

Eye redness or sensitivity to light, burning eyes, eye fatigue, or a dry,
sandy feeling of the eyes

An important consideration in the workup of riboflavin deficiency is that it
can result from a reduction in serum proteins. The appearance of the
symptoms of riboflavin deficiency does not necessarily imply a reduced food
supply. Because riboflavin is transported in the bloodstream as a
flavin-protein complex, nonavailability of the carrier protein also leads to
apparent riboflavin deficiency. Similarly, it is possible for antagonists to
interfere with absorption and/or transport and thus create an apparent
deficiency at receptor sites.
-----------------------------------------------------------------------

http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/rib_0263.shtml

Cruiser

unread,

Oct 20, 2005, 2:41:46 PM10/20/05

Here are some other things that interest me about riboflavin.
-----------------------------------------------------------
http://www.findarticles.com/p/articles/mi_qa3867/is_199811/ai_n8826470

Riboflavin deficiency can cause conditioned deficiency of vitamin B6 and the
mucocutaneous lesions observed in these two vitamins deficiencies could be
due to impaired skin collagen maturity.
------------------------------------------------------------
http://www.moondragon.org/health/nutritionbasics/vitamins/vitaminb2.html

Deficiency symptoms include cracks and sores at the corners of the mouth,
eye disorders, inflammation of the mouth and tongue, and skin lesions, a
group of symptoms collectively referred to as ariboflavinosis. Other
possible deficiency symptoms include, dermatitis, dizziness, hair loss,
insomnia, light sensitivity, poor digestion, retarded growth, and slowed
mental response.

--snip--

Treat Rosacea-related Skin Blemishes. Because riboflavin deficiencies have
been recorded in people with this chronic skin condition, taking a
riboflavin supplement may help. Specifically, riboflavin's ability to
improve the skin's secretion of mucus may aid in clearing up skin pustules
associated with rosacea. In addition, some rosacea sufferers have notably
high numbers of tiny skin mites residing in hair follicles, most likely a
byproduct of an immune-system weakness. Riboflavin, along with other B
vitamins, may help to counter these mites as well.

-------------------------------------------------------------

http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/rib_0263.shtml

The antioxidant activity of riboflavin is principally derived from its role
as a precursor of FAD and the role of this cofactor in the production of the
antioxidant reduced glutathione. Reduced glutathione is the cofactor of the
selenium-containing glutathione peroxidases (see Selenium), among other
things. The glutathione peroxidases are major antioxidant enzymes. Reduced
glutathione is generated by the FAD-containing enzyme glutathione reductase.
Riboflavin deficiency is reported to be associated with compromised oxidant
defense resulting in increased lipid peroxidation. Increased lipid
peroxidation under conditions of riboflavin deficiency, may be accounted
for, in large part, by decreased regeneration of reduced glutathione which
is necessary for the function of the antioxidant glutathione peroxidases.
Riboflavin deficiency may also affect the mitochondrial pool of reduced
glutathione which in turn may affect the activities of the flavoenzymes
NADPH-cytochrome P450 reductase and NADPH-cytochrome b reductase. Elevated
riboflavin levels have been reported to provide protection against oxidative
forms of hemeproteins. Oxidative forms of hemeproteins have been implicated
in reperfusion injury. Riboflavin has also been shown to protect against
reperfusion injury in isolated rabbit hearts. The protection by riboflavin
against oxidative damage caused by oxidized forms of hemeproteins may be
mediated by an NADPH-dependent methemoglobin reductase which is also known
as flavin reductase. In this case, riboflavin itself appears to act as an
antioxidant via its conversion to dihydroriboflavin. Riboflavin has been
found to protect lung and brain, as well as heart, from cellular oxidative
injury, The protection has been proposed to be mediated through flavin
reductase. It has been demonstrated that higher oxidation states of
hemeproteins are rapidly reduced by dihydroriboflavin.

-------------------------------------------------------------

From Hayek:

I used to take very strong doses of B6 for bleeding
gums, in my early twenties. When I take one single
high dosage pill of that now, I get sick and my
liver aches.
-------------------------------------------------------------
Cold sores disappear rapidly with my formula. After
two days the sore is cured, and then heals in a
week. They do not return.
-------------------------------------------------------------
One notices someone sloughing or walking straight, or the
disappearrence of facial skin problems.
-------------------------------------------------------------

Cruiser

randall

unread,

Oct 20, 2005, 3:26:32 PM10/20/05

Hi,

(I posted this two hours ago and it stil hasn't shown. So, you may see
two of
these. Basically the same but this one is better.)

Our first link today brings up age old P questions.

Is there a P gut link to etiology?

Remicade fixes the gut for UC folks. Does that mean less LPS leakage

for psoriasis folks as well? Or does blocking TNF simply close the

loose junctions in the gut? I doublt it, but don't truly know.

Are the mucosal tissues in the gut, the front line for curing P?

Hey!

Fixing my guts (wit kit/proflora whey) seemed to point in that
direction.

And when i do my trials now, i use alcohol to determine efficacy.
As it works so quickly to re-ignite the fires of P.

How else can I tell if my IP6 trial is working? Or am i rationalizing?

You be the judge. Here's the facts,

http://www.cnw.ca/fr/releases/archive/October2005/19/c2947.html
REMICADE(R) Achieves Long-Term Treatment Goals of Mucosal Healing and
Remission in Patients with Ulcerative Colitis

Data Presented at UEGW Meeting Also Demonstrate Reduction in
Hospitalizations
and Improved Quality of Life

<sniP>

**************

While i agree with manfreds assessment on uwe and nac, (found here)
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_frm/thread/957a9357fff1c49b/edbd288651761ee6#edbd288651761ee6

I'm able to make positive connections to my current trial with his
continual examination of the subject. Could my ~6 grams of vitamin C

be the magic with the NAC i'm taking? As to that trial i'm
experimenting with
half a gram to one gram of IP6 a day, every other day for the last few
days.

Being that i'm not willing to stop the half gram of iP6 or the nac,
unless

i forget to take it, i guess i'm hooked on clear. :(

Being clear has screwed uP my objectivity. Sorry folks!

I am trying to keep my eye on the targets i deem imPortant.

But the ethanol has me some what stumPed. Red wine oK, white
not, could it be the drier wines and red wines offer more or what?

And how much does LPS affect psoriasis, if at all? Or does it
only affect the Th1 skew independently of the actual psoriasis genes
and their actions?

Needless to say i'm riding on nearly clear and eating pork 3-5 times
a week and not significantly flaring during this time period. Amazing
to me as for almost my entire life I would flare at the droP of a hat
with
the foods i'm being served.

Back to LPS.

Vanadyl Sulphate (VS) helps recovery from LPS,

http://www.betterhumans.com/News/4722/Default.aspx
&
http://www.innovations-report.de/html/berichte/medizin_gesundheit/bericht-50271.html

So, it indirectly proves LPS leakage should you take 10-20 mcg's and

clear a little? And VS helps with wound healing and growth in youth.

(so?)

But what the heck, alcohol and spices that cause gut leakage in the

colon allow for LPS to leak. Should that be in your P pathway. I've
been as certain as possible
that these are in my general inflammation pathways and must be involved
with the psorasis as to severity.

Btw, I wasn't breastfed. And back then the plain old bottle of sterile
milk had
little if no DHA, which explains my total lack of attention from early
on. :(

How much VS is in breastmilk? <g>

I doubt that uwe and VS has the long hoped for curative properties for
us anyway.
Not like what NAC has done for me. So, has the IP6 allowed greater
usage of
vitamin c (as a stand alone it flares me in the long run) and that has
turbo charged
the NAC, which i've been taking anyway.

***************************^^^^^^^^^^^^^^^^^^^**********************^^^^^^^^^^^^^^

Moving on to another curious and far deadlier immune condition.

While sarcoidosis is rarer then P (1 out of a 1000 or so) and more
prevalent amongst
those that don't get P, (africans) it is worth looking at.

Why?

You tell me.

After reading this link.

More advances

What is Sarcoidosis?

What is the Cause?

What are the Symptoms?

How is it Detected?

^^^^^^^^^

http://www.aafp.org/afp/20020415/1581.html

http://graphics.jsonline.com/graphics/packer/img/news/dec04/db1226a.jpg

http://groups.google.com/group/alt.obituaries/browse_frm/thread/5c388cc37e81d268/20e1727518f529c3?lnk=st&q=Sarcoidosis&rnum=6#20e1727518f529c3

we all become victims in the long run. And looking at Reggie in his hay
days it's
hard to imagine him dying due to antibiotics and little bitty bugs.

Could reggie have been helped with vanadyl sulphate or a skin condition

like ours,

that exfoliates the problems/toxins quicker? Could P be compensatory in
some cases?

???

Or would Reggie and all sarcoidosis patients be better off fixing the
gut mucosal
tissues with the wit kit (thewholewhey.com) and never getting the
resistant bugs
in the first place?

randall... time to exercise a little restraint as to ANTIbiotics.

randall

unread,

Oct 20, 2005, 4:15:19 PM10/20/05

Cruiser wrote:
> "randall" <ranh...@aol.com> wrote in message
> news:1129826399.0...@o13g2000cwo.googlegroups.com...
>
> > i forget to take it, i guess i'm hooked on clear. :(
> >
> > Being clear has screwed uP my objectivity. Sorry folks!
> >
>
> Randall, are you completely clear of P lesions/plaques now?

No, but being in a nearly state is close enough. Normally with what
i'm consuming, I would be real bad.

Maybe 12-34% i'm guessing.

So, at around 1-2% and being really bad, the line blurs a little.

Along with my eyesight. <g> The areas of whitish new skin must
make me somewhat myopic. lol

>
> I do not recall you saying previously that you are completely 100% clear.
>

I haven't. So, i fudged a few percent.

But areas that were plaquish are now slightly red or clear and almost
no flakes.

If i go to town to-nite with three or four glasses of wine (white not
red) those red spots will be slightly flaky by tomorrow.

> You talked about reducing the amount of coverage, but I have not
> seen any previous mention of 100% clear.

Now, i'm begining to feel guilty, like i stole a cookie and
need my hand slaPPed.

So i fudged the line, a degree or two!

>
> I have yet to clear anything, well maybe one small spot.
>
> Right now I am working on the Kreb's cycle. There are some interesting
> things going on related to riboflavin, boron, and the thyroid that I want to
> explore.

Red wine has enough boron and other trace minerals in it doesn't it?
Maybe thats the difference as to why the red doesn't affect as much
as the white.

Could the sugars in white wines augment the permeability factors?

What else explains it?

>
> I seems that thyroxin is produced by the thyroid and this involves iodine
> and manganese. Thyroxin regulates flavokinase, which is needed to make
> FAD and FMN from riboflavin. FAD is important in the Krebs Cycle.

If you really suspect the krebs cycle, find some malic acid. That
would be like your taking methylcobalamin as you avoid 6 or 7 steps
in the process. With the methyl your only saving two?

>
> http://waltonfeed.com/self/health/vit-min/b2.html
>
> Further, high boron supplementation causes riboflavin deficiency.
>
> This could explain why, when I started Boron at high levels, I developed
> some new psoriasis lesions. If so, suggests that low riboflavin in as a
> possible cause of new psoriasis lesions.

Or!

Your gut terrain is the main player in the P game and you've not
done anything to correct that of a significant nature.

Changing the mucosal layers doesn't just haPPen.

You have to do the diet and the implant!

Sorry, butt those are the facts. <g>

>
> I have been reading the information on riboflavin and it has some very
> interesting propeties, that have me now looking very closely at it.
>
> In particular, I have always been particularly sensitive to bright light.
> Unless I wear sunglasses, I find myself squinting on bright sunny days.
> I have never understood this. Why am I more sensitive to bright light
> than most other people?

I use to wear them all the time outside and now I like the light
plain and simple without the glasses.

>
> -----------------------------------------------------------------------
> http://www.emedicine.com/med/topic2031.htm
>
> Eye redness or sensitivity to light, burning eyes, eye fatigue, or a dry,
> sandy feeling of the eyes
>
> An important consideration in the workup of riboflavin deficiency is that it
> can result from a reduction in serum proteins. The appearance of the
> symptoms of riboflavin deficiency does not necessarily imply a reduced food
> supply. Because riboflavin is transported in the bloodstream as a
> flavin-protein complex, nonavailability of the carrier protein also leads to
> apparent riboflavin deficiency. Similarly, it is possible for antagonists to
> interfere with absorption and/or transport and thus create an apparent
> deficiency at receptor sites.
> -----------------------------------------------------------------------
>
> http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/rib_0263.shtml
>

Look, if the terrain in the colon is of a positive nature, the good
bugs will
make the stuff to keep you haPPy/clearer. If not, the immune system
will move south.

The way we need to in order to get the vitamin D. The active form that
is. And not to mention those UV's in the ~308-11 nm range. :)

randall... i'm a lot clearer. Maybe not 100%, but i invite you to come
look!

> Cruiser

randall

unread,

Oct 20, 2005, 4:53:31 PM10/20/05

Hi,

Hot off pubmed.

A new P DNA study, everybody and their mothers are on this one!

Even Doctor's Menter and Ann Bowcock!

So, what does it mean?

Localization of PSORS1 to a haplotype block harboring HLA-C and
distinct from corneodesmosin and HCR.

Helms C, Saccone NL, Cao L, Daw JA, Cao K, Hsu TM, Taillon-Miller P,
Duan S, Gordon D, Pierce B, Ott J, Rice J, Fernandez-Vina MA, Kwok PY,
Menter A, Bowcock AM.

Department of Genetics, Washington University School of Medicine, Box
8232, 4566 Scott Avenue, St. Louis, Missouri, 63110, USA.

Psoriasis is a complex inflammatory disease of the skin affecting 1-2%
of the Caucasian population. Associations with alleles from the HLA
class I region (now known as PSORS1), particularly HLA-Cw*0602, were
described over 20 years ago. However, extensive linkage disequilibrium
(LD) within this region has made it difficult to identify the true
susceptibility allele from this region. A variety of genes and regions
from a 238-kb interval extending from HLA-B to corneodesmosin (CDSN)
have been proposed to harbor PSORS1. In order to identify the minimum
block of LD in the MHC class I region associated with psoriasis we
performed a comprehensive case/control and family-based association
study on 242 Northern European psoriasis families and two separate
European control populations. High resolution HLA typing of HLA-A, -B
and -C alleles was performed, in addition to the genotyping of 18
polymorphic microsatellites and 36 SNPs from a 772-kb segment of the
HLA class I region harboring the previously described interval. This
corresponded on average to one SNP every 7 kb in the candidate 238 kb
region. With all tests, the association was the strongest with single
markers and haplotypes from a block of LD harboring HLA-C and SNP n.9.
Logistic regression analyses indicated that association seen with
candidate genes from the interval such as CDSN and HCR was entirely
dependent on association with HLA-Cw*0602 and SNP n.9-G alleles. The
previously reported association with CDSN and HCR was observed to be
due to the existence of the associated alleles lying on the most
commonly over-transmitted haplotype. Rare over-transmitted haplotypes
also harbored HLA-Cw*12 alleles. HLA-Cw*12 family members are closely
related to HLA Cw*0602, sharing identical sequences in their alpha-2
domains, peptide-binding pockets A, D and E and all 3' introns. The
introduction of a potential binding site for the RUNX/AML family of
transcription factors in intron 7, is also specific to these HLA-C
alleles. These variants need to be investigated further for their role
as PSORS1.

PMID: 16235096

******

I guess it means it needs further studying. Well it does.

They said so.

At least we know it's psor1 in the lead in this horse race.

randall... will LPS the long shot come in from the outside rail?

randall

unread,

Oct 20, 2005, 7:54:42 PM10/20/05

Hi,

Some old natural cures die hard. Some don't die but can kill you.

Take this strange case for you CSi folks out there,
Severe cyanide toxicity from 'vitamin supplements'

O'brien B, Quigg C, Leong T.

Department of Anaesthesia, Our Lady's Hospital for Sick Children,
Dublin, Ireland.

The use of alternative medicines is increasing and poorly regulated. We
describe a case of severe cyanide poisoning arising from amygdalin, a
putative vitamin supplement. A 32-year-old woman arrived in the
emergency department by ambulance unresponsive, shocked and with fixed
dilated pupils. She was hypothermic and tachycardic but was breathing
spontaneously. Despite her age, she had documented breast cancer with
hepatic metastases. Conventional treatment having failed, she only took
'vitamin supplements' bought on the Internet, her father said. Over the
next 6 h she required mechanical ventilation and increasing doses of
inotropes. Diabetes insipidus developed. As the appropriateness of
further treatment was considered, a relative arrived with her
medications including 'vitamin B 17' or amygdalin. An Internet search
identified this as a debunked cancer remedy and cyanogen. Serum
thiocyanate level was markedly elevated. She recovered fully over 8 h.
While various antidotes to cyanide exist, in this case supportive
therapy alone proved effective.

PMID: 16175068

Good thing this poor womens liver was stll working! She'd be hanging
with Saint Peter otoh.

Back in the old days people flocked to TJ mexico to the cancer clinics
for this stuff.
If you were dying, what did you have to lose?

Yet, if you only had lowly psoriasis, was there a there there for you?

There may have been and we didn't even know it.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16232308
Immunomodulatory effects of a set of amygdalin analogues on human
keratinocyte cells.

Baroni A, Paoletti I, Greco R, Satriano RA, Ruocco E, Tufano MA, Perez
JJ.

Department of Experimental Medicine, Microbiology and Clinical
Microbiology Section, Second University of Naples, Naples, Italy.

Peptide T (PT) is an octapeptide shown to resolve psoriatic lesions.
Our previous investigations suggest that keratinocytes play an
important role in conditioning the therapeutic effects of the PT in
psoriasis. However, peptides are not good therapeutic agents, because
they exhibit poor absorption, are easily metabolized and are
immunogenic. Using computational methods, the natural product amygdalin
was identified as peptidomimetic of PT. However, amygdalin exhibits a
toxic profile due to its cyanide group. To overcome this deleterious
effect, we synthesized analogues lacking the cyanide group. Human
keratinocytes were treated with PT or with three different
peptidomimetics of PT. To study its effects on the expression of
HSP-70, TGF-beta, alpha-v integrin, ICAM-1 and cytokines, we analysed
the protein levels by Western blot and ELISA. Our results show that the
different peptidomimetics of PT tested exhibit a similar biological
behaviour in regard to the overexpression of HSP-70, TGF-beta and
alpha-v integrin than the native peptide. TNF-alpha is overexpressed by
PT and SVT-03018; between the other two analogs, SVT-03016 do not
produce any significant change in regard to the control, while
SVT-03017 shows only a moderate increase in regard to control.
SVT-03018 provokes a remarkable upregulation of IL-10, stronger than
SVT-03016, SVT-03017 and PT. All the other three analogues reduce
comparably to the PT, the expression of ICAM-1 and do not increase the
release of proinflammatory cytokines. The results highlighted that the
three analogues of amygdalin with the cyanide group removed exhibit the
same biological effects of PT. Therefore, they can be considered
peptidomimetics, suggesting their possible use in the treatment of
psoriasis.

PMID: 16232308

H'mmm some of these same folks, from the abstract above, worked on this
one,
Synthesis and evaluation of diverse analogs of amygdalin as potential
peptidomimetics of peptide T.

Araya E, Rodriguez A, Rubio J, Spada A, Joglar J, Llebaria A, Lagunas
C, Fernandez AG, Spisani S, Perez JJ.

RUBAM, Dept. de Quimica Organica Biologica, (IIQAB-CSIC), Jordi Girona
Salgado, 18-26, E-08034 Barcelona, Spain.

Peptide T (ASTTTNYT) is a promising molecule to prevent the
neuropsychometric symptoms of patients suffering AIDS and for the
treatment of psoriasis. In order to fully prove its therapeutic
benefits, efforts were put forward to design peptidomimetics of the
peptide. In this direction, in a recent computational study the natural
product amygdalin was identified as a prospective peptidomimetic of the
peptide and later proved to exhibit a similar chemotactic profile to
the peptide. However, the cyanide moiety of amygdalin provides to the
molecule a toxic profile. The present study reports the synthesis of a
set of amygdalin analogs lacking the cyanide group with improved
chemotactic profiles.

PMID: 15713414

How does one get this stuff outa the pits? Chewing uP aPricot pits
isn't exactly easy! Hence the saying, "it's the pits".

Isolation and quantitation of amygdalin in Apricot-kernel and Prunus
Tomentosa Thunb. by HPLC with solid-phase extraction.

Lv WF, Ding MY, Zheng R.

Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology, Ministry
of Education, Department of Chemistry, Tsinghua University, Beijing
100084, P.R. China.

Apricot-kernel and Prunus Tomentosa Thunb. are traditional Chinese herb
medicines that contain amygdalin as their major effective ingredient.
In this report, three methods for the extraction of amygdalin from the
medicinal materials are compared: ultrasonic extraction by methanol,
Soxhlet extraction by methanol, and reflux extraction by water. The
results show that reflux extraction water containing 0.1% citric acid
is the best option. The optimal reflux is 2.5 h and water bath
temperature is 60 degrees C. The solid-phase extraction method using
C18 and multiwalled carbon nanotube as adsorbents is established the
pretreatment of reflux extract, and the result shows that the two
adsorbents have greater adsorptive capacity for amygdalin and good
separation effect. In order to quantitate amygdalin in Apricot-kernel
and Prunus Tomentosa Thunb., a reversed-phase high-performance liquid
chromatography method using methanol-water (15:85, for 30 min and pure
methanol after 30 min) as mobile phase is developed and a good result
is obtained.

PMID: 16176653

Ok, so besides maybe slowing down P, what else is it good for?

Cancer anyone? What are you nuts?

Nope. This stuff may still be a winning horse in the cancer race.

Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon
cancer cells.

Park HJ, Yoon SH, Han LS, Zheng LT, Jung KH, Uhm YK, Lee JH, Jeong JS,
Joo WS, Yim SV, Chung JH, Hong SP.

Department of Oriental Pharmaceutical Sciences, College of Pharmacy,
Kyung Hee University, Seoul 130-701, South Korea. seon...@khu.ac.kr.

AIM: The genes were divided into seven categories according to
biological function; apoptosis-related, immune response-related, signal
transduction-related, cell cycle-related, cell growth-related, stress
response-related and transcription-related genes. METHODS: We compared
the gene expression profiles of SNU-C4 cells between amygdalin-treated
(5 mg/mL, 24 h) and non-treated groups using cDNA microarray analysis.
We selected genes downregulated in cDNA microarray and investigated
mRNA levels of the genes by RT-PCR. RESULTS: Microarray showed that
amygdalin downregulated especially genes belonging to cell cycle
category: exonuclease 1 (EXO1), ATP-binding cassette, sub-family F,
member 2 (ABCF2), MRE11 meiotic recombination 11 homolog A (MRE11A),
topoisomerase (DNA) I (TOP1), and FK506 binding protein
12-rapamycin-associated protein 1 (FRAP1). RT-PCR analysis revealed
that mRNA levels of these genes were also decreased by amygdalin
treatment in SNU-C4 human colon cancer cells. CONCLUSION: These results
suggest that amygdalin have an anticancer effect via downregulation of
cell cycle-related genes in SNU-C4 human colon cancer cells, and might
be used for therapeutic anticancer drug.

PMID: 16127745

But what if i'm taking 5-6 grams of vitamin C and have cancer and i'm
68 years old?

Yikes,

Life-threatening interaction between complementary medicines: cyanide
toxicity following ingestion of amygdalin and vitamin C.

Bromley J, Hughes BG, Leong DC, Buckley NA.

Department of Clinical Pharmacology and Toxicology, The Canberra
Hospital, Garran, Australia. jonathan...@act.gov.au

OBJECTIVE: To describe a case of severe accidental cyanide poisoning
following a single ingestion of amygdalin with therapeutic intent. CASE
SUMMARY: A 68-year-old patient with cancer presented to the emergency
department shortly after her first dose (3 g) of amygdalin with a
reduced Glasgow Coma Score, seizures, and severe lactic acidosis
requiring intubation and ventilation. The patient also ingested 4800 mg
of vitamin C per day. She responded rapidly to hydroxocobalamin
treatment. The adverse drug reaction was rated probable on the Naranjo
probability scale. DISCUSSION: Amygdalin and laetrile (a synthetic form
of amygdalin) are commonly used as complementary or alternative
medicine (CAM) for the treatment of cancer. Vitamin C is known to
increase the in vitro conversion of amygdalin to cyanide and reduce
body stores of cysteine, which is used to detoxify cyanide. Amygdalin
has been used for decades by patients with cancer who are seeking
alternative therapies, and severe reactions have not been reported with
this dose. An interaction with vitamin C is a plausible explanation for
this life-threatening response. CONCLUSIONS: This case highlights the
fact that CAMs can produce life-threatening toxicity. This case also
adds a further note of caution, namely, the potential for serious
interactions between CAMs, particularly where there is no tradition of
concomitant use.

PMID: 16014371

^^^^^^^^^^^^^^^^^^^^

There you go. The cyanide must be removed before using.

Will it end up in a toPical cream?

If it clears P that would be awesome.

randall....

cruiser

unread,

Oct 20, 2005, 11:13:50 PM10/20/05

"randall" <ranh...@aol.com> wrote in message

news:1129839319.3...@o13g2000cwo.googlegroups.com...

> So, at around 1-2% and being really bad, the line blurs a little.
>

So now you are about where I have been for a few years.

I improved considerably, when I had my mercury fillings removed.
I dropped from 4-5% down to 1-2%.

Now, I have found a chemical mercury connection. I don't know if this
will pan out, but what I found is that besides mercury mysteriously
causing candidiasis, mercury disrupts the thyroid and can make you
hypothyriod. This means less thyroxin, which means less FMN and FAD.

This means that even though you consume adequate supply of riboflavin,
you can have deficiency symptoms.

I have now learned what to do about getting rid of mercury and fixing
my thyroid.

Kelp (iodine), maganese, selenium, zinc and copper, boron (3mg only)
with an emphasis on more selenium, to bind the mercury into an inert
compound.

I am also supplementing magnesium and molybdenum. Minerals
need to be balanced. Calcium, I get from dairy. I consume lots of
milk, yogurt, cheese, and ice cream. Our water also has much calcium.

I am also supplementing riboflavin, B1, B2, B3, B5, B6, B12,
Folic acid, and biotin in large doses.

I take some of the flax/cottage cheese/garlic mix when I get
home in the evening with some Ip6 and B vitamins, to provide
phospholipids for cell membranes, to make new red blood cells
and T-Cells, to heal, and to potentially repair cells membranes
damaged by oxidation, due to riboflavin deficiency.

This should fix my thyroid, crank up the krebs cycle, improve
my new blood quality, and improve my hormone levels. Improve
the processing of fatty acids, and reduce oxidatve damage to
the cell membranes, improving permiability to gases and other
exchanges.

I am also taking lots TMG, Calcium D-glucarate, NAC, and
reduced glutathione, to support my liver in detoxifying the
excess amounts of supplments that I take and to help rid my
body of any other toxins. I am supporting every liver detox
channel except taurine conjugation.

If I have remaining mercury involvement, this should hopefully
blow it away and allow me to eliminate the mercury factor.

Other supplements that I am using are Chlorella,
phosphadytilcholine, green tea, whey protein shake, and IP6.

I am also trying that mushroom thingy that works with the
calcium D-glucarate.

I also drink two or three 8 ounce glasses of orange juice
per day and eat a raw unpeeled carrot.

I won't be keeping this up for much longer. I am really
feeling much better, in many ways, but have yet to see a
significant improvement in psoriasis.

Since I just started the mecury/thyroid/krebs/riboflavin therapy,
I will continue on that track for a while. This is just the first day
for that. I should have a better idea if it is helping in a couple
days.

Cruiser

randall

unread,

Oct 21, 2005, 2:03:59 AM10/21/05

cruiser wrote:
> "randall" <ranh...@aol.com> wrote in message
> news:1129839319.3...@o13g2000cwo.googlegroups.com...
>
> > So, at around 1-2% and being really bad, the line blurs a little.
> >
>
> So now you are about where I have been for a few years.
>
> I improved considerably, when I had my mercury fillings removed.
> I dropped from 4-5% down to 1-2%.
>

Next to nothing happened for me when I had mine out. And that
was around 20 or so fillings over six or seven years ago.

Right after that I did the colostrum six month stint (or so) and
then found thewholewhey.com.

> Now, I have found a chemical mercury connection. I don't know if this
> will pan out, but what I found is that besides mercury mysteriously
> causing candidiasis, mercury disrupts the thyroid and can make you
> hypothyriod. This means less thyroxin, which means less FMN and FAD.
>

I have a late onset parent who takes thyroid meds.

I don't think there's a correlation that i can find anyway.

> This means that even though you consume adequate supply of riboflavin,
> you can have deficiency symptoms.
>

If you did you'd serious enough problems that psoriasis would be
lower on the list, it would seem.

> I have now learned what to do about getting rid of mercury and fixing
> my thyroid.

Lets go back to the bug and antibiotics thing,

This morning I was anti antibiotic, (now i'm not?)
http://www.abc.net.au/wa/stories/s1487053.htm
Possible arthritis cure?

Thursday, 20 October 2005

Presenter: Liam Bartlett

A former WA medical researcher could be on the verge of finding a cure
for rheumatoid arthritis and related diseases.

Dr Trevor Marshall is now Director of the Auto-immune Research
Foundation in California. He's about to enter the formal phase three
trials testing a potential breakthrough which began at Sir Charles
Gairdner Hospital.

It was in the late 1970s that the doctor found that patients with
diabetes had symptons suggesting a relationship with other diseases.

Nowadays, he's found that sarcoidosis, chronic fatigue, rheumatoid
arthritis, and even psoriasis are related and helped by the same
therapy.

As Dr Marshall describes it: "There is a special type of antibiotic
resistant bacteria which are present in these patients, and when these
bacteria are killed, the patient's symptoms goes away."

It's all to do with a graduated cocktail of antibiotics gradually
clearing the bacteria out of the body. Trevor Marshall names one drug
that isn't readily available in Australia, but there's nothing tricky
about the others. "It's just standard stuff," says our guest, "Generic
drugs that may be ten cents a capsule or something."

Whilst the doctor stresses that his research still needs to pass its
third series of trials, he feels that something new is at hand. "All of
these diseases are basically diseases which physicians try to maintain
the status quo...to have the possibility of actually restoring the
health of the patient is a huge step forward."

Arthritis sufferers stay tuned.

You need a real player for the link and to go to that link.

As heard on the Mornings with Liam Bartlett.

The information presented here is designed to provide an overview of
the subject and should be used as a guideline only. This information
does not take the place of proper diagnosis or treatment from a
qualified health practitioner. Please consult your health professional
for treatment advice.
Related Links:
Some of these links may be to sites outside the ABC and as such the ABC
has no editorial control over such sites.

http://marshallprotocol.com
Dr Trevor Marshall acknowledges that the secret to the success of his
work to date has been his interactive website. You can find further
details there.

**************

Ok so lets do some P news while i'm at it.

Cuban mud to clear P. But you can't get it unless you live in the
Domican Republic or Spain.
http://www.granma.cu/ingles/2005/octubre/juev20/43cosmeticos.html

The seven skin sins and tips to improve the skin,
http://health.dailynewscentral.com/content/view/0001804/31/

******

Ok, back to your post.

>
> Kelp (iodine), maganese, selenium, zinc and copper, boron (3mg only)
> with an emphasis on more selenium, to bind the mercury into an inert
> compound.

Maybe it is a gut bug that requires mucho antibiotics.

In that case my gut trip may keep them under enough control to
clear. And the vitamin C and iron chelating IP6 augment that
control to clear even more?

Or the vitamin C is turboing the nac to work better.

>
> I am also supplementing magnesium and molybdenum. Minerals
> need to be balanced. Calcium, I get from dairy. I consume lots of
> milk, yogurt, cheese, and ice cream. Our water also has much calcium.
>

Save me some. Love good water. But dairy was always more or less
a problem. Could it be that i'm killing enough of those bugs
that i can now eat it without it acting as such a strong trigger?

Yet the terrain of your gut isn't changed in the least?

StraPPing a turbo charger on a plain old motor doesn't help
it to re-build itself in the long run.

If the gut is the first line of defence, then you may not get the
bang for your buck that you expect.

OTOH, if it is a bug then it still needs our funky genes to work
through?

randall... Funny isn't it? How i can fliP floP 180 degrees in a day?
>
> Cruiser

Cruiser

unread,

Oct 21, 2005, 9:52:03 AM10/21/05

"randall" <ranh...@aol.com> wrote in message

news:1129874639.3...@g43g2000cwa.googlegroups.com...

>
> If you did you'd serious enough problems that psoriasis would be
> lower on the list, it would seem.
>

I am not so sure. I am thinking a long term marginal defiency.

I find that on dry winter mornings, I get white stains, like dried
toothpaste,
around the corners of my mouth. This seems like it could be B2 related.

Well that is interesting and possibly good news. Let's see how it pans out.

> ******
>
> Ok, back to your post.
> >
> > Kelp (iodine), maganese, selenium, zinc and copper, boron (3mg only)
> > with an emphasis on more selenium, to bind the mercury into an inert
> > compound.
>
> Maybe it is a gut bug that requires mucho antibiotics.
>
> In that case my gut trip may keep them under enough control to
> clear. And the vitamin C and iron chelating IP6 augment that
> control to clear even more?
>

Well I am considering that your triggers and cause may be different
than mine. However, if the mercury/thyroid/B2 thing does not work
out, I may back off most of what I am taking and reduce to just
IP6, vitamin C, NAC, reduced glutathione, tmg, and
calcium D-glucarte. I am already including those things, so I would
be just cutting out all the other stuff.

> Or the vitamin C is turboing the nac to work better.
>

I am drinking 2-3 8 ounce glasses of orange juice a day, which is
a ton of vitamin C. I also take IP6 (6x600mg) a day. I take
2400 mg NAC, 1000mg reduced glutathione, about 1800mg
Calcium D-glucarate, and about 3 grams TMG.

I got that covered. I has not helped yet.

>
> Save me some. Love good water.

Our water is well water and is very good tasting, but the calcium
carbonate tends to stain the glassware cloudy white. My wife is
considering a water softener.

> Yet the terrain of your gut isn't changed in the least?
>

Say what!? Not so!

You are just not following my line of reasoning and my plan.

I am not looking to control gut flora directly, clear related toxins, and
hope for the best after that.

I read somewhere that the mucosa re-surfaces itself every couple days. That
would mean that new cells have to be made continually.

Providing the phospholipids for healthy new cell walls and ensuring that the
new cells have lots of the essential nutrients to make really good cells is
definitely a support strategy for the gut. In addition, riboflavin is
supposed to protect cell walls from oxidative damage by promoting reduced
glutathione in cells. The gut is a toxic environment, and the mucosa is
normally equipped to deal with the toxins. A shorage of reduced glutathione
in the mucosa makes it open to damage by toxins. B2 shortage is supposed to
negatively affect mucus tissues. They mention the tissues inside the mouth,
but the mucosa also fits the definition. My gut support strategy is to
improve the gut lining cell quality, boost my mucosa cell toxin defense, and
boost my immune system to help keep my mucosa intact. My immune support
strategy is to fix my thyroid hormones, and support the manufacture of
T-Cells, with the essential building blocks. I am also supplementing to turn
over homocysteine and reduce cortisol, which should also boost my immune
system. Further, the B vitamins, phospholipids, and other nutrients should
also improve the quality of new blood cells and improve total body cell
respiration, including immune related cells and the mucosa. All these things
should combine to help out with repairing and protecting my mucosa, and to
fight off any infections.

That is my gut support strategy. I am not out to kill things in the gut with
chemicals, I am out to repair and protect the mucosa, so that even bad gut
flora cannot negatively impact it. The gut will always be full of thousands
of different kinds of mirco organisms. A good mucosa should contain them and
keep them under control.

A couple more days of following this plan should give me a better idea if I
am on the correct track.

Cruiser

cruiser

unread,

Oct 21, 2005, 11:09:31 PM10/21/05

Just found this on riboflavin converted to FMN. A shortage of FMN can
prevent some genes from turning off. The conversion is regulated by
thyroxin, which can be in short supply under conditions of mild
hypthyrodism, due to mercury, or any other factor that could lead to
hypothyroidism.

Research Highlights
----------------------------------------------------------------------------
----

Nature Chemical Biology
Published online: 22 April 2005 | doi: 10.1038/nchembio012

RNA Biochemistry
Gene regulation
ribD activation in the balance
Terry L Sheppard
----------------------------------------------------------------------------
----
Wickiser et al. suggest that activation of a flavin-binding riboswitch is
regulated by balancing transcriptional and ligand binding rates.
----------------------------------------------------------------------------
----
http://www.nature.com/nchembio/journal/vaop/nprelaunch/full/nchembio012.html

The idea that small molecules could regulate gene expression at the nucleic
acid level has been an intriguing biochemical hypothesis for decades. The
recent identification of riboswitches, which are ligand-responsive RNA
elements found in regulatory regions of genes, has provided insights into
how small molecule metabolites may directly regulate expression of
biosynthetic genes. Wickiser et al. recently reported, in Molecular Cell,
that a flavin mononucleotide (FMN) riboswitch from Bacillus subtilis is
controlled by a delicate balance of transcriptional rates and ligand binding
kinetics

Riboswitches are naturally occurring RNA regulatory elements that are
activated by binding of a specific small molecule ligand, which triggers a
structural reorganization of the RNA and alters gene expression. The ribD
riboswitch is one of two FMN-responsive RNA elements in B. subtilis. ribD
resides upstream of the genes that code for riboflavin biosynthesis. Thus,
when FMN is plentiful, it binds to ribD RNA and switches off the downstream
biosynthetic genes. Previous work suggested that ribD regulates gene
expression by a transcriptional antiterminator-terminator mechanism (Fig.
1). Under low FMN concentrations, ribD RNA is folded in the antiterminator
conformation, which permits transcription of downstream genes. However,
under high FMN concentrations, FMN binds to the aptamer domain and
rearranges the ribD expression platform to a classical RNA terminator
stem-loop, which blocks transcriptional elongation and turns the genes off.

---and more---

Cruiser

randall

unread,

Oct 22, 2005, 1:36:52 PM10/22/05

cruiser wrote:
> Just found this on riboflavin converted to FMN. A shortage of FMN can
> prevent some genes from turning off. The conversion is regulated by
> thyroxin, which can be in short supply under conditions of mild
> hypthyrodism, due to mercury, or any other factor that could lead to
> hypothyroidism.

Then taking a grain or two of thyroid meds should clear us?

But it doesn't.

So back to DNA. That is an area that may help us some day.

What did they learn recently?

How about junk dna (non-coding),
http://www.the-scientist.com/news/20051020/01
&
http://www.sciencedaily.com/releases/2005/10/051020090946.htm

>
> Research Highlights
> ----------------------------------------------------------------------------
> ----
>
> Nature Chemical Biology
> Published online: 22 April 2005 | doi: 10.1038/nchembio012
>
> RNA Biochemistry
> Gene regulation
> ribD activation in the balance
> Terry L Sheppard
> ----------------------------------------------------------------------------
> ----
> Wickiser et al. suggest that activation of a flavin-binding riboswitch is
> regulated by balancing transcriptional and ligand binding rates.
> ----------------------------------------------------------------------------
> ----
> http://www.nature.com/nchembio/journal/vaop/nprelaunch/full/nchembio012.html
>

<sniP>

And just think how many ribo switches doing the right thing you'll have
after you grow a killo of good flora in the colon?

And even the stats should normalize long enough to clear a patch or
two!

randall.. doing the gut tangO with fortitude!
>
> Cruiser

cruiser

unread,

Oct 23, 2005, 1:30:40 PM10/23/05

"randall" <ranh...@aol.com> wrote in message

news:1130002612....@o13g2000cwo.googlegroups.com...

>
> cruiser wrote:
> > Just found this on riboflavin converted to FMN. A shortage of FMN can
> > prevent some genes from turning off. The conversion is regulated by
> > thyroxin, which can be in short supply under conditions of mild
> > hypthyrodism, due to mercury, or any other factor that could lead to
> > hypothyroidism.
>
>
> Then taking a grain or two of thyroid meds should clear us?
>
> But it doesn't.
>

Yess I found this:
------------------------------------------------------------
http://www.euchromatin.net/Lai01.htm

Repressors of Vitamin-Related Gene Expression: No Smoking Gun

The machinery responsible for synthesizing and/or importing a wide variety
of essential small molecule
metabolites and vitamin cofactors in bacteria is under negative feedback
control. When availability of such small molecules is low, the
transcription/translation of the relevant genes to allow their synthesis or
import is activated. Conversely, in times of plenty, there is no need to
maintain high level production or import capability, and the relevant genes
are down regulated.
------------------------------------------------------------

I looks like a case of homeostatically controlled vitamin cofactor
production, a feedback mechanism.

In any case, I recall that my doctor told me four years ago, when I had a
complete physical that my thyroid was a bit low. I did not think it was
important. I figured it was a matter of normal aging. He did not seem to
think it was important. Now I am wondering.

Cruiser

cruiser

unread,

Oct 23, 2005, 3:46:35 PM10/23/05

"randall" <ranh...@aol.com> wrote in message

news:1130002612....@o13g2000cwo.googlegroups.com...

> Then taking a grain or two of thyroid meds should clear us?
>
> But it doesn't.
>

Do you know of any study?

I am wondering if psoriasis might be dependent on a process with many
chemical pathways contributing. If you are deficient along any of those
contributing pathways, then the process is is limited by the deficient
pathway. So, JR may be defient is omegas, so omegas clear the process
limiter for him. Now Jane is deficient along some other contributing pathway
and so using something else might fix her up. So, now Bill has a genetic
predisposition to an absoprtion problem or maybe a hormone problem, and that
messes up some other pathway. So, Bill says, it may work for you, but I
tried JR and Jane's things and it did not work for me.

I am really serious thinking, that low glutathione in the mucosa, a
potentially very toxic place with hundreds of foreign organisms thriving is
close proximity, is not a good thing. Seriously weekened cellular defences
will weeken the whole mucosa and leave it open to opportunistic infections.
The toxins will simply corrode the mucosa, and the most responsive
infectious agent will begin to take roots. Candida appears to be one such
most common agent, but others may do better under different circumstances.
There may even be a combination of infections at different places along the
mucosa.

This leads me to suggest that you have your thyroid levels checked, since
chronic slightly low thyroxin could lead to low levels of activated
riboflavin. That process limits glutathione defense in cells. Glutathione
protects the phospholipids in the cell membrane, the primary building block
of the cell membrane. It is not that you would have none, but you would have
less than normal, since you have less activate fiboflavin.

So instead of having a Glutathione Guard at every three feet on you castle
wall, you have a Glutathione Guard every fifty feet. So, then you get sick
or don't eat the right stuff, and your Glutathione Guards are down to one
every 150 feet. The moguls hordes storm the castle and overwhelm the
defenses.

If you do not fix the root cause, which is thyroid deficiency and/or diet
short on riboflavin, you will never never get well. You can repeatedly kill
fungal infections and or bacterial infections, but they will just keep
coming back.

Kelp, riboflavin, reduced glutathione, and boron.

If you have had mercury exposure, add selenium, manganese, copper, zinc,
magnesium, molybdenum, and calcium, using selenium in higher doses compared
to the others. Minerals need to be balanced, they tend to compete with each
other too. So, taking extra of one can cause a shortage of another.

You really want the selenium to bind with the mercury, forming a stable
compound, that ends up stored in fat where the mercury is neutralized, and
can no longer affect chemical processes. At the same time you want copper
and zinc, because mercury competes with copper and zinc and that is how it
inhibits thyroid function. The other minerals are supplemented to keep a
mineral balance.

Your infection is not gone, but what caused you to get the infection is
gone. You still have to kill off the infection, since they tend to rupture
the mucosa and cause the leaky gut. The infection can spread to other parts
of the body, xenotoxins, xenoproteins and cell fragments get into the blood.

So, you still have to kill off the infection, get the mucosa intact, and
have the Glutathione Guard stationed every three feet.

So what if you don't have a thyroid problem? Then is may be diet related
only. Then riboflavin and reduced glutathione.

A shortage of phospholipids may be a problem too, since they are the stones
in your castle walls.

So, this is my line of investigation.

Cruiser

JXStern

unread,

Oct 23, 2005, 5:57:49 PM10/23/05

On Sun, 23 Oct 2005 15:46:35 -0400, "cruiser"
<tg.cr...@sympatico.ca> wrote:
>I am wondering if psoriasis might be dependent on a process with many
>chemical pathways contributing. If you are deficient along any of those
>contributing pathways, then the process is is limited by the deficient
>pathway. So, JR may be defient is omegas, so omegas clear the process
>limiter for him. Now Jane is deficient along some other contributing pathway
>and so using something else might fix her up. So, now Bill has a genetic
>predisposition to an absoprtion problem or maybe a hormone problem, and that
>messes up some other pathway. So, Bill says, it may work for you, but I
>tried JR and Jane's things and it did not work for me.

The inflammation process probably overloads a number of normal
pathways, and can in turn be supported or repressed by diet and drugs,
but is not itself the cause, nor likely the cure, for the basic
immune-triggered condition.

There is probably immense variation in (a) the genetic mechanisms (if
six or eight genes, and several variations of each, might be
involved), (b) the environmental situations each person encounters
that sets off one or more possible triggers, and (c) the dietary
habits that person has.

So, it's easy to get a few minor, but real, improvements, but they
won't work for everyone, and they seldom solve the whole problem.

Not to mention that shutting off too much of the immune or
inflammatory system has plenty of its own dangers, whether you do it
with Enbrel or diet.

Fun for all.

cruiser

unread,

Oct 24, 2005, 10:58:45 PM10/24/05

"JXStern" <JXSternC...@gte.net> wrote in message
news:sj1ol156ainrjt36k...@4ax.com...

> On Sun, 23 Oct 2005 15:46:35 -0400, "cruiser"
> <tg.cr...@sympatico.ca> wrote:

> The inflammation process probably overloads a number of normal
> pathways, and can in turn be supported or repressed by diet and drugs,
> but is not itself the cause, nor likely the cure, for the basic
> immune-triggered condition.
>

I really don't think that there is an actual cure, not in the sense that you
can change your genes to halt your propensity to manifest psoriasis
symptoms, under the right conditions, but I am thinking that there may
be ways to eliminate those conditions.

It has been done many times by people with it works-for-me stories.

All of us, at one time did not manifest psoriasis symptoms. Our genes
were the same then as they are now. Even I, for whom symptoms
came as a child, was psoriasis free for my earliest years.

I would be happy to just eliminate all the symptoms, and any related
infections.

Cruiser

cruiser

unread,

Oct 25, 2005, 8:47:15 AM10/25/05

cruiser

unread,

Oct 25, 2005, 8:48:54 AM10/25/05

Oops!! Typo.

That should read thyroxin. Correted below.

"cruiser" <tg.cr...@sympatico.ca> wrote in message
news:VAp7f.4593$ki7.2...@news20.bellglobal.com...

> More on riboflavin, thyroid and liver.
>

> Seems that thyroxin and riboflavin are need to convert folic acid to

cruiser

unread,

Oct 25, 2005, 9:32:10 AM10/25/05

A good page on ribolfavin.

The code prevents you from doing a cut and paste from the page, so you have
to go there and read it.

------------------------------------

http://www.amgnetwork.com/ms/vit-b2.htm

------------------------------------

Cruiser

cruiser

unread,

Oct 25, 2005, 2:14:14 PM10/25/05

Sorry,

I guess I should expound a bit on where I am going with this.

Critical:

1) Thyroid function may limit amounts of activated riboflavin

2) Activated riboflavin is essential to activate folic acid, which is
important for coverting homocysteine to SAMe and for making RNA.

3) Activated riboflavin is essentail to activate vitamin B6, which is
essential to make reduced glutathione. Activated B6 also aids in preventing
non-enzymatic glycosylation, which mainfests as wrinkles, the need for
reading glasses, age spots, stiffening ligaments and stiffening arteries.

4) Activated riboflavin is essential in the Krebs cycle.

SAMe is an important methyl donor which activates many processes in the
body. It also is used with activated B6 to make glutathione, so, a shortage
of activated riboflavin will limit glutathione production in two ways. Less
SAMe due to a shortage of activated folic acid, and less activated B6.

Glutathione is one of the body's main detoxifing pathways. A shortage means
toxins cannot be as effectively eliminated by the liver.

Further, glutathione acts as a protector of the phospholipids that compose
the cell membrane. Glutathione protects the cell membrane from oxidation,
but then is oxidized itself in the process. FMN a form of activated
ribroflavin reduces glutathione by taking away that oxidate. This recycles
glutathione so it can be reused.

One of the body's responses to low FMN levels is to produce more reduced
glutathione, but it cannot do that as effectively as previously discussed,
due to a shortage of SAMe and activated B6.

This leaves the mucosa, the intestinal lining, with less reduced glutathione
for defence against oxidation, since a shortage of activated riboflavin
cannot as thoroughly reduce(recylce) the existing glutathione, and it limits
the amount of new reduced glutathione the body can synthesize. That may
allow oxidative corrosion of the mucosa cell membranes, and leave the mucosa
vulnerable to opportunistic infection.

Opportunistic infection can penetrate the mucosa causing a systemic
infection, and may cause leaky gut, with xenotoxins entering the blood
stream and systemic infection producing xenotoxin in other parts of the
body, then causing problems with glutathione shortage in those locations,
while also requiring additional reduced glutathione to clear those toxins
through the liver.

So, bottom line. Hypothyroid condition will cause reduced levels of
activated riboflavin, leading to the chain of events described above. The
severity will depend on the degree of hypothyroid condition.

Further, the resultant elevated homocysteine will lead to high blood
pressure and supressed immune system. Also, hypothyroid condition will mean
reduced thyroid hormone production, which will further depress immune
response. This means that opportunistic infection can more readily spread.

Further, hormone shortfalls and SAMe shortage will have system wide
implication for many processes and can affect immune and mental function.

A shortage in the Krebs cycle of activated riboflavin will result in poor
physical performance.

Since activated riboflavin activates folic acid, a shoratge of acitvated
folic acid will contribute to RNA depletion and slow production of needed
proteins and cofactors.

Finally, oxidated cell membranes will be less effective at transporting
gases and nutrients in and out of cells. Cell respiration, feeding, and
waste elimination will be affected.

If thyroid function is normal, dietary shortage of riboflavin and/or
glutathione precursors may be a factor.

One of the symtoms of activate riboflavin deficeincy - dry scaling skin.

Another is occular bright light sensitivty.

Rosacea may be related to a shortage of activated riboflavin, since
activated riboflavin is known to reduce the presence of bumps in rosacea.

Activated riboflavin is also needed to process fatty acids, and a shortage
can lead to the accumulation of fat.

One last comment. Hypothyroidism has been implicated in some cases of
erectile dysfunction.

Cruiser

"cruiser" <tg.cr...@sympatico.ca> wrote in message

news:6fq7f.4611$ki7.2...@news20.bellglobal.com...

randall

unread,

Oct 26, 2005, 11:02:17 PM10/26/05

cruiser wrote:
> Sorry,
>
> I guess I should expound a bit on where I am going with this.
>
> Critical:

OK, i'll try!

>
> 1) Thyroid function may limit amounts of activated riboflavin

Then your ahead of the curve? Did you do the pubmed on it?

Lets do the groups,
http://groups.google.com/groups?q=low+thyroid+psoriasis&qt_s=Search

Low thyroid only, (brings the adrenals up some)
http://groups.google.com/groups?q=low+thyroid&qt_s=Search

I don't know. If there is a there there, then like with
immune drugs wouldn't we have seen something already?

>
> 2) Activated riboflavin is essential to activate folic acid, which is
> important for coverting homocysteine to SAMe and for making RNA.

As long as we are making rna/dna for everything else, why pick
on this pathway/process for P only?

If the rna process is suspect in the plaques only, then it's
mechanical due to the genes or bugs. Same as with parkinsons's
and every other immune mediated inflammatory disease (IMID).

It just doesn't make sense otherwise. Does it?

>
> 3) Activated riboflavin is essentail to activate vitamin B6, which is
> essential to make reduced glutathione. Activated B6 also aids in preventing
> non-enzymatic glycosylation, which mainfests as wrinkles, the need for
> reading glasses, age spots, stiffening ligaments and stiffening arteries.
>

Now your on to something. But what? Low glutathione can be corrected,
i've done it millions of times, so i know now. lol

Ok, ok, sorry for the impertinence. What your saying is phase II
enzymes
are overburdened perhaPs? But who isn't with the crap we all eat?

Isn't that why some of us have tried to increase digestive factors and
eaten low inflammation diets etc?

And whats the outcome? Sure you may lower P/inflammation a little. But
hardly worth much to most psoriatics as the loss of life quality is
more severe then the P!

IOWs you have to be pretty severe to really hang on to a vegetarian
regime
like the pagano diet.

> 4) Activated riboflavin is essential in the Krebs cycle.

Krebs smebs! I hardly feel there's anything wrong with krebs. Go buy
some
malic acid like i mentioned before. You skip like six steps in
the process. What are there eight or nine? Whatever, but your
not going to do much. Been there, done that.

Want me to do it one more time?

I can do that next with the IP6/vitamin C/ Nac thing.

Whoops, i forgot my supplements with supper this eve.

Ok, took them. I was off today.

I'm noticing that everyone i know with P is flaring early this
fall....

>
> SAMe is an important methyl donor which activates many processes in the
> body.

And the amount of SAMe your taking is nothing compared to what your
liver is churning out 24/7. Your taking mg's and your liver is making
grams each day!

Obviously, to me anyway, folks who need it are so borderline, that
a few tweaks in lifestyle should correct any problems poste haste.

> It also is used with activated B6 to make glutathione, so, a shortage
> of activated riboflavin will limit glutathione production in two ways. Less
> SAMe due to a shortage of activated folic acid, and less activated B6.
>
> Glutathione is one of the body's main detoxifing pathways. A shortage means
> toxins cannot be as effectively eliminated by the liver.
>

Once again. This is wandering in to the naturopath paradigm. If it was
only 20% more effective, more of us would be chirPPPing about it.

And you would be hearing from more folks cleared by the local
naturopath.

I'm not hearing it.

> Further, glutathione acts as a protector of the phospholipids that compose
> the cell membrane. Glutathione protects the cell membrane from oxidation,
> but then is oxidized itself in the process. FMN a form of activated
> ribroflavin reduces glutathione by taking away that oxidate. This recycles
> glutathione so it can be reused.

Lets get down to the basics. Science regarding inflammation on the
cellular level is allowing a clearer picture of the TH1 skewings
concerned with all
I.M.I.Ds. At this time we can't even say with certainty that
these Ai conditions aren't compensatory for a bug or due to the cause
of
a gene. But we are as close as possible without getting burned
at the present time. lol

Next year at this time i'm betting we'll know. Well, i will.

>
> One of the body's responses to low FMN levels is to produce more reduced
> glutathione, but it cannot do that as effectively as previously discussed,
> due to a shortage of SAMe and activated B6.
>

In theory ok. But easily testable, right?

> This leaves the mucosa, the intestinal lining, with less reduced glutathione
> for defence against oxidation, since a shortage of activated riboflavin
> cannot as thoroughly reduce(recylce) the existing glutathione, and it limits
> the amount of new reduced glutathione the body can synthesize. That may
> allow oxidative corrosion of the mucosa cell membranes, and leave the mucosa
> vulnerable to opportunistic infection.

Ok, now your in my area. What do you want to know?

Is it a gut thing or a gene thing in the skin or both?
If so then look at a rube goldberg process and test
each pathway. Haven't i done that?

And where do I end uP? Right back at the Genes i can't test
for, duh! Suffice it to say Dr. Bowcock has that covered.

How many more trials do you need?

Their last one looked like a pin the tail on the P gene to me.

What? Really? Let me see that in pubmed. Hold on,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15117377
This is backwards. Goes to show you can't even believe in some pubmed
abstracts.

Hey! Some other randall did riboflavin and P studies in 1951,
http://www.inchem.org/documents/jecfa/jecmono/v16je21.htm

Come to think of it, so did i and found no changes with all the other
supplements i used it with. Not to mention trying various topical
applications as well. :(

I'm going for the topical IP6 next.

>
> Another is occular bright light sensitivty.
>
> Rosacea may be related to a shortage of activated riboflavin, since
> activated riboflavin is known to reduce the presence of bumps in rosacea.

Oh boy, less bumPs.

>
> Activated riboflavin is also needed to process fatty acids, and a shortage
> can lead to the accumulation of fat.
>

Well then. I never had any problems there till I hit the down hill
slide.

> One last comment. Hypothyroidism has been implicated in some cases of
> erectile dysfunction.

So, your looking for the UWE connection here?

For the record, all three of the males with P in my immediate
family never had any problems in that area. Yet, i've never had
low thyroid and my P was the worst.

So, can i do a complete test of your theory by taking riboflavin?

Or do i have to do the whole laundry list?

randall... it's not a B- vitamin thing is it?

cruiser

unread,

Oct 27, 2005, 8:02:52 PM10/27/05

Randall,

I am going with that approach using supplements, for now, but still digging.

Here is my latest area of exploration.

---------------------------------------------------------
http://content.febsjournal.org/cgi/content/full/271/12/2408

Metallothioneins (MTs) release bound metals when exposed to nitric oxide.

--snip--

The presented results show clearly that the metal release from MT2 by nitric
oxide and peroxynitrite is suppressed by reduced but not oxidized
glutathione.

--snip--

Metallothionein has also been shown to protect eukaryotic cells from the
cytotoxic and DNA-damaging effects of nitric oxide [29]. So, while the
binding of NO to GSH in vivo does not obviously prevent NO from interacting
with MT2, we have shown that in vitro it suppresses the metal release from
metallothioneins. This points to an hitherto unknown mechanism or
compound(s) being involved in this interaction in living cells and
information about this additional factor is needed in order to perform
physiologically relevant future in vitro studies and in the interpretation
of results obtained from in vivo experiments on the NO-MT interaction.

---------------------------------------------------------
http://www.pointarrow.com/article53650.html

MT synthesis is induced by copper, cadmium, mercury, gold [40], and also by
glucocorticoids, interferons, IL-1, endotoxins, ethanol [119] and stress.

Cruiser

cruiser

unread,

Oct 28, 2005, 12:27:16 AM10/28/05

Might be something interesting here, about Metallothioneins, and it all
keeps coming up with reduced glutathione and cysteine. NAC will do nicely
for the last.

http://www.cf.ac.uk/biosi/staff/kille/Models/RatMT3.html

Cruiser

"cruiser" <tg.cr...@sympatico.ca> wrote in message

news:6Gd8f.12449$Nj3.1...@news20.bellglobal.com...

randall

unread,

Oct 28, 2005, 1:29:53 PM10/28/05

cruiser wrote:
> Might be something interesting here, about Metallothioneins, and it all
> keeps coming up with reduced glutathione and cysteine. NAC will do nicely
> for the last.

And the first for that matter.

Let's see! Whose Watson here? Did I take the first clue from you?

http://groups.google.com/groups?q=Metallothionein+psoriasis+support&qt_s=Search

Or was it all only suPPort? Read the whole thread on the first link. :)

Gee, even mentions krebs in the response to your laundry list back in
2001.

Now thats a real sPace ODYSSEY. LOL

That could have been written yesterday?

Krebs Smebs?
>
> http://www.cf.ac.uk/biosi/staff/kille/Models/RatMT3.html

The ONOO and nonono threads had to come from somewhere,
http://groups.google.com/groups?q=peroxynitrite+psoriasis+support&qt_s=Search

And NAC has been looming large,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=nac&qt_g=1&searchnow=Search+this+group

How long do we have to go around in circles?

I'll answer that. Till we find the one thing that accomplishes the
mission!

CLEAR! ?.

(((((((((((((((((((((((((((((((((((**))))))))))))))))))))))))))))))))

Back to P news?

Hey! It's your day!, (tomorrow anyway!)
http://sev.prnewswire.com/health-care-hospitals/20051018/SFTU13918102005-1.html

************

On World Psoriasis Day, Astron Clinica launches Psoriasis Manager to
help medical professionals and patients track treatment progress
objectively

http://sourcewire.com/releases/rel_display.php?relid=23108&hilite=
Scientifically track your P. <sniP>

How come we don't have world P day on Halloween? We could kill two
birds with
one stone.

*****************

The best offense is a good defense.

Clobex gets FDA approval,
http://www.medadnews.com/News/Index.cfm?articleid=285357
(...)

CLOBEX(R) Spray was demonstrated to be safe and effective in two multi-
center, randomized, double-blind studies involving 209 patients with
moderate- to-severe psoriasis. In the first clinical trial, 82% of
patients became clear or almost clear after four weeks of treatment,
with 47% of these subjects becoming clear or almost clear in as early
as two weeks. In a second study, 78% of patients were clear or almost
clear after four weeks.

"CLOBEX(R) Spray will be a welcome option for the millions of psoriasis
patients who struggle with their treatment regimen," said Albert
Draaijer, President, Galderma Laboratories, L.P. "The product's vehicle
has been specifically designed to efficiently deliver clobetasol
propionate to the skin. Above and beyond its unsurpassed efficacy, the
easy application of this advanced vehicle will allow even the most
active psoriasis patients to remain compliant with their therapy."
Available by prescription in a 2 fl oz bottle, the twice-daily use
product should be applied directly on the lesion(s), avoiding the
surrounding skin. Clobetasol propionate has been shown to suppress the
HPA axis at the lowest doses tested.
<sniP>

**************

Did this one get away? With it? lol

The really, really BIG P fish story,
http://www.practicalfishkeeping.co.uk/pfk/pages/item.php?news=759

A student from Scotland claims that her skin condition has been cured
by sitting in a bath of fish which nibbled at her skin.

Samantha Locke from Jordanhill in Glasgow, who suffers from the skin
condition psoriasis, told The Daily Mail that after sitting in a bath
full of fishes, the scales, which are symptomatic of the condition, had
disappeared from her skin.

Locke, who came across the treatment while on a spa holiday in Turkey,
says the Mail, sat in a sunken bath full of cyprinid fishes called
Garra rufa for over an hour. When she got out of the bath, the reddish
patches and silvery scales left by the inflammatory condition were
getting better.

"It felt strange knowing they were eating my skin..."

She told The Daily Mail: "It felt strange knowing they were eating my
skin but I couldn't feel them touching me.

"It was weird the way the fish were only nibbling at the bits affected
by psoriasis."

<sniP>

*********
Dermatologist Alan Menter discusses psoriasis with a patient in the
film "My Skin's on Fire." (Courtesy: Fred Finkelstein)

Coming to a scream near you?

http://abcnews.go.com/Health/Health/story?id=1253231

********************

Where does the whole P thing start? Is it dna? Is there a trigger?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1642072

Is the miscreant X factor of P, willing to be attenuated by NAC or IP6?

Does it take a Merlin to untrick the sPell?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16252236

randall... Trick or teat?

cruiser

unread,

Oct 29, 2005, 1:05:51 PM10/29/05

Randall,

So, here is what I figure out of this, so far.

The thyroid thing may be related to a boron deficiency, but can also be
affected by a shortage of cysteine to bind up the toxic metals and to
regulate the good metals, and by a shortage of reduced glutathione to keep
the metals bound,. The metals can be released by NO gas and oxidative
stress. The effects of the released metals is lots more oxidate stress,
interfering with mitochondrial respiration, and corroding the mucosa due to
the toxic environment.

Cysteine is needed to make grams of SAMe, it is needed to make RNA, it is
needed to make glutahione, it is needed to make MTs, and it is needed in
many proteins. It seems that cycsteine could be in very high demand.

Glutathione protects against oxidation, but we have seen vitamin C described
as the blanket anti-oxidant, which even reduces glutathione. Taking high
does vitamin C will doubtless conserve cycsteine, by reducing glutathione
and thereby recycling it. It will also reduce the oxidative interence with
mitochonrial respiration, and protect the mucosa from oxidative stress.

High does vitamin C and NAC, makes much sense, and the effects may help to
heal the mucosa by reducing oxidative corrosion, improving thyroid function
by binding toxic metals and regulating good metals, providing glutathione
for liver and cell detoxification, and by providing building material for
new proteins.

So, say 6-7 grams vitamin C and a bunch of NAC seems like a very good
combination of supplements for chronic infection. How much NAC, is the
question.

In addtion, you might consider some B vitamins. Some good metals, may be
needed too, 3mg boron, 50mg zinc, 100mcg selenium, 15mg manganese, 300mg
magnesium, 3mg copper, iodine.

IP6? You seem to feel this helps by reducing excess iron.

I am using the flax seed - low fat cottage cheese thing too.

Cruiser

unread,

Oct 31, 2005, 10:19:03 AM10/31/05

Randall,

Found this in one of your blanket searches.

http://groups.google.com/group/alt.support.breast-implant/browse_frm/thread/884b5ed2407003e4/2d308c35e4103d0c?tvc=1&q=Metallothionein+psoriasis+support#2d308c35e4103d0c

Current available literature indicates a risk for metal-induced
autoimmunity in man. Metal pathology may be due to toxic or allergic
mechanisms where both may play a role. The main factors decisive for
disease induced by metals are exposure and genetics which determine
the individual’s detoxifying capacity and sensitivity to metals.
This paper reviews the possible mechanisms which may play a role in
metal-induced autoimmunity with the emphasis on multiple sclerosis
(MS), rheumatoid arthritis (RA) and amyotrophic lateral sclerosis
(ALS). We also discuss the role of inflammation-induced changes in the
hypothalamus-pituitary- adrenal (HPA) axis as a possible explanation
of fatigue, depression and other psychosomatic symptoms observed in
these diseases.

--snip--

As shown previously, mercury can be found in the thyroid gland [139].
Patients with psoriasis and atopic eczema improved following the
reduction of metal exposure by diet low in metal ions or by dental metal
replacement in metal-sensitive patients [140, 141].

--snip--

Thus the ability to detoxify xenobiotics together with the individual
susceptibility to the metal are probably the most important factors in
the outcome of metal exposure.

Cruiser

"cruiser" <tg.cr...@sympatico.ca> wrote in message

news:4LN8f.8465$ki7.7...@news20.bellglobal.com...

randall

unread,

Nov 1, 2005, 3:53:44 PM11/1/05

Hi,

http://www.medadnews.com/News/Index.cfm?articleid=286199

CHARLOTTE, N.C., Nov. 1, 2005 (PRIMEZONE) -- Chelsea Therapeutics
International, Ltd. (OTCBB:CHTP), has accepted an invitation to speak
at the Rodman & Renshaw Techvest 7th Annual Healthcare Conference at
4:55 p.m. EST Monday, November 7th, at the New York Palace Hotel.

Dr. Simon Pedder, president and CEO of Chelsea Therapeutics, will
provide a company overview and update on the status of its current
clinical development programs, including the clinical trial of its lead
compound, CH-1504.

A live webcast of the presentation can be accessed on the investor
relations page of the company's website, www.chelseatherapeutics.com.
The presentation will also be archived shortly after the live event and
available online for 90 days following the conference.

About CH-1504

In March 2004, Chelsea acquired the exclusive rights to a number of
antifolate compounds, including CH-1504, its lead product candidate.
These compounds lack the specific metabolism associated with side
effects known to occur with marketed antifolates such as methotrexate
(MTX). Chelsea is continuing to develop CH-1504 as a treatment for RA,
psoriasis, IBD, cancer and other immunological disorders.
An independent six-month pilot clinical study compared CH-1504 to
methotrexate, the current standard of care, in 20 RA patients in Peru.
Although the pilot study will not be used as a part of the U.S.
regulatory approval process, the results of this study suggest that
CH-1504 has lower toxicity and improved tolerability, as well as
potentially increased efficacy versus methotrexate. Pre-clinical animal
models have also indicated that CH-1504 may have superior efficacy and
a greater therapeutics window than methotrexate. Methotrexate currently
accounts for almost half of the prescriptions written for the RA market
<sniP>

^^^^^^^^^

http://www.medadnews.com/News/Index.cfm?articleid=286216
Bioaccelerate, Inc.: Proven, Effective Treatment for Psoriasis Now in
Clinical Development in North America

(...)

GenaDerm, a specialty dermatological company, is in the race to provide
better therapies for more effective treatment of psoriasis. GenaDerm is
a subsidiary of Bioaccelerate Holdings Inc. (OTCBB:BACL). The privately
held company is co-developing with Immunotech Developments Inc., for
Thymodepressin(r) the first synthetic peptide developed for the
treatment of autoimmune diseases including psoriasis. Immunotech is a
biotechnology-focused firm that works to develop novel therapeutic
peptides for the treatment of large market diseases.

Now in clinical development and testing in North America,
Thymodepressin(r) has already proved to be an effective treatment for
psoriasis in Russia, where the drug was invented and is currently sold.

Professor Vladislav Deigin, Chief Executive Officer and President of
Immunotech and inventor of Thymodepressin(r) said, "Immunotech was
established to pursue the development and commercialization
opportunities presented by a scientific platform for the identification
and production of peptides. We are delighted that this has been the
basis of developing an effective treatment for such a chronic and
debilitating condition. Key therapeutic goals in the treatment of
psoriasis are alleviation of the condition, and sustainability of the
relief provided by treatment. After successfully treating many
psoriasis patients in Russia we are optimistic that clinical trials
will confirm this efficacy in other countries."

<sniP>

^^^^^^^^^^^^^^^^^^^^

Abstracts in the P news today,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16258194
Serum Levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and
IL-18 in Patients With Active Psoriasis and Correlation With Disease
Severity.

Arican O, Aral M, Sasmaz S, Ciragil P.

Recent progress in the understanding of psoriasis has shown that the
regulation of local and systemic cytokines plays an important role in
its pathogenesis. The most often used psoriasis score is the psoriasis
area and severity index (PASI). A simple laboratory test from a blood
sample would be an attractive, patient-independent, and
observer-independent marker of disease severity. To this end, we
evaluated the association of serum levels of some proinflammatory
cytokines in vivo and their correlation with severity of psoriasis. The
serum levels of cytokines levels were determined with the use of the
ELISA method. All mean values except IL-17 levels of patients were
significantly higher than those of controls. There was a significant
correlation between serum levels of IFN-gamma, IL-12, IL-17, and IL-18,
and severity of the disease. Psoriasis can be described as a
T-cell-mediated disease, with a complex role for a variety of
cytokines, which has led to the development of new immunomodulatory
therapies. In this study, serum TNF-alpha, IFN-gamma, IL-6, IL-8,
IL-12, and IL-18 levels were significantly higher in active psoriatic
patients than in controls. Furthermore, high levels of IFN-gamma,
IL-12, and IL-18 correlated with the clinical severity and activity of
psoriasis, and those measurements of serum levels of these cytokines
may be objective parameters for the disease severity.

PMID: 16258194

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16257373

Keynote review: Phosphodiesterase-4 as a therapeutic target.

Houslay MD, Schafer P, Zhang KY.

Division of Biochemistry & Molecular Biology, IBLS, Wolfson Link
Building, University of Glasgow, University Avenue, Glasgow, G12 8QQ,
Scotland, UK.

Cyclic AMP (cAMP) is a key second messenger in all cells. It is
compartmentalized within cells and its levels are controlled, as a
result of spatially discrete signaling cassettes controlling its
generation, detection and degradation. Underpinning compartmentalized
cAMP signaling are approximately 20 members of the phosphodiesterase-4
(PDE4) family. The selective inhibition of this family generates
profound, functional effects and PDE4 inhibitors are currently under
development to provide potential, novel therapeutics for the treatment
of inflammatory diseases, such as asthma, chronic obstructive pulmonary
disease and psoriasis, as well as treating depression and serving as
cognitive enhancers. Here, we delineate the range of PDE4 isoforms,
their role in signaling, their structural biology and related
preclinical and clinical pharmacology.

PMID: 16257373

I wonder what we have on it?
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=pde4&qt_g=1&searchnow=Search+this+group

not much, lets try the entire groups for it,
http://groups.google.com/groups?q=Phosphodiesterase-4&qt_s=Search

***********

Quantification of absolute peripheral white blood cells and their
subsets in patients with lupus erythematosus: comparison with other
inflammatory diseases with and without autoimmune background.

Bohm I.

Department of Radiology, University of Bonn, Sigmund-Freud Strasse 25,
53105 Bonn, Germany.

To test the value of decreased peripheral leuko-/lymphocytes as
screening test for the diagnosis lupus erythematosus (LE). Laboratory
routine analyses, and flow cytometry (CD3, CD4, CD8) have been
performed in 124 LE-patients. Other subjects included 57 healthy
controls, 130 patients with non-autoimmune inflammatory diseases
(dermatitis, psoriasis), and 17 patients with another autoimmune
disease (progressive systemic sclerosis [PSS]). Numbers of peripheral
blood leukocytes (P<0.0005), lymphocytes (P<0.00002), CD3+, and CD3+
CD4+ cells from LE-patients were significantly lower than from
controls, patients either with dermatitis, psoriasis or PSS. CD3+ CD8+
cells were significantly diminished in patients with LE and PSS.
Decreased numbers of white blood cells, lymphocytes and some of their
subsets seem to indicate LE. Patients with PSS only had decreased
T-cytotoxic cells. Inflammatory dermatoses lacking the autoimmunity as
background have normal cell counts. For screening purpose absolute
values of the mentioned blood cell subsets seem to be useful to
distinguish both autoimmunity from non-autoimmune inflammatory
diseases, and LE from PSS.

PMID: 16256301

***********

randall...

cruiser

unread,

Nov 1, 2005, 6:44:23 PM11/1/05

"randall" <ranh...@aol.com> wrote in message

news:1130878424.6...@g44g2000cwa.googlegroups.com...

So what does effective treatment mean?

Look at this....
---------------------------

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=10604994&dopt=Citation

Synergistic effects of IL-4 and IL-18 on IL-12-dependent IFN-gamma
production by dendritic cells.

Fukao T, Matsuda S, Koyasu S.

Department of Microbiology and Immunology, Keio University School of
Medicine, Tokyo, Japan.

Mouse splenic dendritic cells (DCs) produce IFN-gamma in response to IL-12.
In the present study, we analyzed effects of Th1 and Th2 cytokines on
IFN-gamma production by DCs. IL-18 produced by DCs and macrophages acts in
an autocrine manner and augments IL-12-induced IFN-gamma production by DCs
as also observed in T and NK cells. Surprisingly, IL-4, a Th2 cytokine, also
acts synergistically with IL-12 on IFN-gamma production by DCs. In addition,
IL-4 markedly enhances IFN-gamma production when DCs are stimulated through
CD40 or MHC class II. These results indicate that both Th1 and Th2 cytokines
act on DCs during T cell-DC interaction upon Ag presentation. p38
mitogen-activated protein kinase is constitutively activated in mature DCs
and is required for IFN-gamma production by DCs. IL-18 but not IL-4 or IL-12
further activates the p38 mitogen-activated protein kinase activity,
suggesting that IL-4 and IL-18 enhance IFN-gamma production through distinct
intracellular signal transduction pathways in DCs.
--------------

So hopefully, that means at least our dendritic cells are well and active.

Cruiser

cruiser

unread,

Nov 1, 2005, 6:59:04 PM11/1/05

"randall" <ranh...@aol.com> wrote in message
news:1130878424.6...@g44g2000cwa.googlegroups.com...

>
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Ab

Check this out...

-------------------------
http://iai.asm.org/cgi/content/abstract/65/9/3594

Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal
activity of murine peritoneal exudate cells against Cryptococcus neoformans
through production of gamma interferon by natural killer cells
T Zhang, K Kawakami, MH Qureshi, H Okamura, M Kurimoto and A Saito
First Department of Internal Medicine, Faculty of Medicine, University of
the Ryukyus, Okinawa, Japan.

We examined the ability of interleukin-12 (IL-12) and IL-18 to induce the
production of gamma interferon (IFN-gamma) and nitric oxide (NO) by murine
peritoneal exudate cells (PEC) and to stimulate the growth- inhibitory
activity of these cells against Cryptococcus neoformans. PEC produced
IFN-gamma and NO when stimulated with a combination of IL-12 and IL-18 but
little or no IFN-gamma or NO when either cytokine was used alone. PEC
anticryptococcal activity was mediated by IFN-gamma and NO production, since
it was completely inhibited by a neutralizing anti- IFN-gamma monoclonal
antibody (MAb) and N(G)-monomethyl-L-arginine, a competitive inhibitor of NO
synthesis, respectively. To identify the IFN-gamma-producing cells among PEC
stimulated with IL-12 and IL-18, we depleted NK cells, gammadelta T cells,
or CD4+ T cells by treating PEC with specific Abs and complement. NK cell
depletion strongly suppressed IFN-gamma production and almost completely
inhibited NO production and anticryptococcal activity, while depletion of
other cells had no such influence. Alternatively, purified NK cells by two
cycles of glass adherence and magnetic separation with anti-CD3, -CD4, -CD8,
and -B220 MAbs produced a greater amount of IFN-gamma by stimulation with
IL-12 and IL-18 than unseparated non-glass-adherent PEC. Our results
demonstrated that IL-12 and IL-18 synergistically induced NO-dependent
anticryptococcal activity of PEC by stimulating NK cells to produce IFN-
gamma.

------------------------------------------

So by natural killer cells, NK, I am thinking they mean dendritic cells, DC.
So, these markers indicate a dendritic cell attack on fungus, probably due
to a lack of T-cell defense. I am guessing that it is a fallback defense.

Cruiser

cruiser

unread,

Nov 1, 2005, 7:10:36 PM11/1/05

"cruiser" <tg.cr...@sympatico.ca> wrote in message

news:i4T9f.4824$LF3.4...@news20.bellglobal.com...

> So by natural killer cells, NK, I am thinking they mean dendritic cells,
DC.
> So, these markers indicate a dendritic cell attack on fungus, probably due
> to a lack of T-cell defense. I am guessing that it is a fallback defense.

I guess not, NK cells sem to be another type of immune cell. So, I guess
dendritic cells and NK cells both can do the same thing. In any case it
looks like a defense against fungus.

Cruiser

randall

unread,

Nov 1, 2005, 9:09:13 PM11/1/05

cruiser wrote:
> "cruiser" <tg.cr...@sympatico.ca> wrote in message
> news:i4T9f.4824$LF3.4...@news20.bellglobal.com...
>
> > So by natural killer cells, NK, I am thinking they mean dendritic cells,
> DC.
> > So, these markers indicate a dendritic cell attack on fungus, probably due
> > to a lack of T-cell defense. I am guessing that it is a fallback defense.

We've gone over FUN Gus many times.
>
> I guess not,

What? Is that a gut felt decision?

http://groups.google.com/group/alt.philosophy/browse_frm/thread/e6c7f7292b1f9427/fd11d2c2431627ca?lnk=st&q=enteric+nervous+system&rnum=6#fd11d2c2431627ca

And how much control does the second brain have for immune mediated
inflammatory disorders (I.M.I.Ds)?

> NK cells sem to be another type of immune cell. So, I guess
> dendritic cells and NK cells both can do the same thing. In any case it
> looks like a defense against fungus.

You must have missed some of my lengthier posts that had all of
this at some point or other,

http://www.nearingzero.net/screen_res/nz109.jpg

We are getting ahead of our selfs as stem cells may be the ultimate
answer,
http://cmgm.stanford.edu/biochem118/images/Stem%20Cell%20Slides/04%20Pluripotent%20Stem%20Cells.jpg

And from there we go back to the T-lymphocytes,
http://www2.mc.duke.edu/depts/surgery/gencell/pictures/Stem%20cell.gif

Who is mister DC?
http://www.uni-regensburg.de/Fakultaeten/Medizin/HaemOnko/Forschung/Englisch/Mackensen/DC.jpg
Call him sPiky. Sticks like glue to you know who?

DC meets mister T and can go one way or the other,
http://www.uni-regensburg.de/Fakultaeten/Medizin/HaemOnko/Forschung/Englisch/Mackensen/TcellRegG.jpg
&
http://www.madsci.org/posts/archives/Apr2003/1051378426.Im.r.html
Th1/Th2,
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th1_Th2.gif
( http://www.iir.suite.dk/IIR/04MO/MO.htm )
( http://www.iir.suite.dk/IIR/03Th/Th.htm ) has Th0/Tr Th3
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th_B.gif

A good overview,
http://users.path.ox.ac.uk/~scobbold/tig/tolg2.html

All leading back to us,
http://ard.bmjjournals.com/cgi/content/full/64/suppl_2/ii30/F1
http://ard.bmjjournals.com/content/vol64/suppl_2/images/large/ar31120.f2.jpeg
http://ard.bmjjournals.com/cgi/content/full/64/suppl_2/ii30

And you can't forget biocarta (i use it often),
http://groups.google.com/groups?q=biocarta+psoriasis&qt_s=Search

Oh wait? Did I get the right thing or not?

randall... doing my impression of a white cell now.

>
> Cruiser

randall

unread,

Nov 2, 2005, 11:52:14 AM11/2/05

Hi,

http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/11-02-2005/0004206337&EDATE=

Site Aims to Be the Drug-Free Psoriasis Resource

REDMOND, Wash., Nov. 2 /PRNewswire/ -- Question: Where can
psoriasis
patients and their families go to learn more about the common skin
disease and
effective natural treatments for it? Answer: Nowhere -- until today.
With the
goal of offering the largest psoriasis information site not run by big
pharmaceutical companies, SaltWorks(TM), Inc. (http://www.saltworks.us)
has
launched PsoriasisRx.com (http://www.psoriasisrx.com).
Mark Zoske, founder of SaltWorks, saw the need for such a site when
customers began reporting improvement after using SaltWorks' Dead Sea
salt-
based products to treat their psoriasis.
"We have spoken with so many customers over the years that have
purchased
our Bokek(TM) Dead Sea salt and ReliefRx Psoriasis Treatment program to
help
with their psoriasis," Zoske explained. "We created PsoriasisRx.com as
a
reference point for various types of psoriasis and various treatments,
with a
particular focus on safe and natural alternative treatments. The
current
treatments most doctors prescribe for their psoriasis patients are
pretty
frightening."
For that reason, PsoriasisRx.com provides free, comprehensive
information
about specific types of psoriasis, along with updates on psoriasis
treatments
and news about research advances. An extensive resource section
includes links
to medical journals, the National Psoriasis Foundation and its
counterparts
around the world, psoriasis discussion forums and support groups, and
other
psoriasis-related sites. PsoriasisRx.com is updated regularly with
relevant
information for psoriasis patients, their friends and families, and
their
health care providers.
Nothing on PsoriasisRx.com is provided or sponsored by large drug
manufacturers -- and Zoske aims to keep it that way, opting instead to
create
an unbiased source of information about the condition and offer
alternatives
to harsh prescription psoriasis treatments.
"We hope PsoriasisRx.com is a gift of empowerment through
education," said
Zoske. "Our team is dedicated to providing accessible, widespread, and
accurate information free of charge to expand the public's
understanding of
psoriasis."

About SaltWorks(TM), Inc.
Founded in 2001 by Mark Zoske, SaltWorks imports premium gourmet
sea salts
and bath salts and supplies them to the wholesale, retail, and consumer
markets throughout North America. SaltWorks customers range from
individuals
that order by the pound to manufacturers, restaurants, food co-ops, and
health
food stores that order by the pallet. The Seattle-area company
maintains a
strong commitment to providing the cleanest, most natural products
possible.

Contact:

Mark Zoske
SaltWorks(TM), Inc.
425-885-7258
ma...@saltworks.us
http://www.psoriasisrx.com

This release was issued through eReleases(TM). For more
information,
visit http://www.ereleases.com.

*******************************

I didn't look thru the site. I may try the gourmet salt. On my meat.
lol

How much difference can there be between salts?

Not a lot. Unless it's dead sea salt? And clears a flake or two.

randall...

Big Bill

unread,

Nov 2, 2005, 7:47:44 PM11/2/05

Well there is the kind of salt you put on your meat and potatoes and
the kind of salt you take to dampen the effects of your being manic
depressive. Quite a difference there, I would imagine, two very
different members of the salt family.

BB
--
www.kruse.co.uk/ s...@kruse.demon.co.uk
Elvis does my SEO

randall

unread,

Nov 7, 2005, 3:12:44 PM11/7/05

Hi,

P news from around the world.

http://seattletimes.nwsource.com/html/businesstechnology/2002608431_drugnc07.html
Artist grows increasingly ill in test

By Liz Willen and David Evans

Bloomberg News

By the time Bill Hamlet dropped out of a clinical trial of Genentech's
Raptiva in December 2000, the 58-year-old artist and woodcarver could
barely walk or stand.

Thick red scabs from a severe outbreak of psoriasis covered his legs,
back and torso. Blood stained his sheets and clothing. Before entering
the study, Hamlet says he was in good health. He took the medication
methotrexate to control psoriasis and a mild case of psoriatic
arthritis, a condition causing inflammation of the skin and joints.
In his half year in the trial, Hamlet was first given a placebo, a
substance with no active medicine, and then an experimental drug. He
says that when he consented to join the test, no one told him his
psoriatic arthritis could worsen if he got a placebo
<sniP>

****************

Current abstracts.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16269612

CD43 is a ligand for E-selectin on CLA+ human T cells.

Fuhlbrigge RC, King SL, Sackstein R, Kupper TS.

Department of Dermatology, Brigham and Women's Hospital, Boston, MA,
USA.

The recruitment of memory T cells from blood into tissues is a central
element of immune surveillance and adaptive immune responses and a key
feature of chronic cutaneous inflammatory diseases such as psoriasis
and atopic dermatitis. Human memory T cells that infiltrate skin
express the ____carbohydrate____ epitope cutaneous
lymphocyte-associated antigen (CLA). Expression of the CLA epitope on T
cells has been described on P-selectin glycoprotein ligand-1 (PSGL-1)
and associated with the acquisition of both E-selectin and P-selectin
ligand functions. In this report, we show that CD43, a sialomucin
expressed constitutively on T cells, can also be decorated with the CLA
epitope and serve as an E-selectin ligand. CLA expressed on CD43 was
found exclusively on the high molecular weight (125 kD) glycoform
bearing core-2 branched O-linked glycans. CLA+ CD43 purified from human
T cells supported tethering and rolling in shear flow via E-selectin
but did not support binding of P-selectin. The identification and
characterization of CD43 as a T cell E-selectin ligand distinct from
PSGL-1 expands the role of CD43 in the regulation of T cell trafficking
and provides new targets for the modulation of immune functions in
skin.

PMID: 16269612

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=266600

A number sign (#) is used with this entry because of evidence that
mutations in the CARD15 gene (605956) are associated with
susceptibility to Crohn disease in families linked to chromosome 16. An
allele of the ABCB1 gene is associated with susceptibility to Crohn
disease (171050.0003). Other loci for IBD include IBD2 (601458) on
12p13.2-q24.1, IBD3 (604519) on 6p, IBD4 (606675) on 14q11-q12, IBD5
(606348) on 5q31, IBD6 (606674) on 19p13, IBD7 (605225) on 1p36, and
IBD8 (606668) on 16p not linked to CARD15. Polymorphism in the DLG5
gene (604090), which maps to 10q23, is associated with the risk of
developing IBD; genetic interaction studies suggested interactions
between the 113A variant of DLG5 gene (604090.0001) and risk-associated
CARD15 alleles (see 604090.0001-604090.0003). A haplotype defined by a
missense substitution in SLC22A4 (604190.0002) and a G-to-C
transversion in the SLC22A5 promoter (603377.0017) is associated with
susceptibility to Crohn disease.

Inflammatory bowel disease is characterized by a chronic relapsing
intestinal inflammation. IBD is subdivided into Crohn disease and
ulcerative colitis (191390) phenotypes. Crohn disease and ulcerative
colitis have a combined prevalence of 200 to 300 per 100,000 in the
United States. Crohn disease may involve any part of the
gastrointestinal tract, but most frequently the terminal ileum and
colon. Bowel inflammation is transmural and discontinuous; it may
contain granulomas or be associated with intestinal or perianal
fistulas. In contrast, in ulcerative colitis, the inflammation is
continuous and limited to rectal and colonic mucosal layers; fistulas
and granulomas are not observed. In approximately 10% of cases confined
to the rectum and colon, definitive classification of Crohn disease or
ulcerative colitis cannot be made and are designated 'indeterminate
colitis.' Both diseases include extraintestinal inflammation of the
skin, eyes, or joints.

Crohn disease and ulcerative colitis are commonly classified as
autoimmune diseases. The prevalence of inflammatory bowel disease is
increased in individuals with other autoimmune diseases, particularly
ankylosing spondylitis, psoriasis, sclerosing cholangitis, and multiple
sclerosis.

<sniP>
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605619

*605619 Links
INTERLEUKIN 20; IL20

Gene map locus 1q32
TEXT

Blumberg et al. (2001) searched EST databases using an algorithm
designed to identify translated sequences containing both a signal
sequence and 1 or more amphipathic helices commonly found in helical
cytokines. They identified a single EST from a human keratinocyte
library and cloned the corresponding gene, interleukin-20 (IL20), by
3-prime RACE experiments on RNA isolated from human skin and trachea.
The 176-amino acid IL20 protein contains 6 conserved cysteine residues
and shares 76% amino acid identity with its murine counterpart. Based
on amino acid identities, IL20 is most homologous to 3 members of the
IL10 family, IL19 (605687; 40% identity), MDA7 (604136; 33% identity),
and IL10 (124092; 28% identity). Northern blot analysis detected IL20
transcripts at very low levels in skin, trachea, and other tissues.
Blumberg et al. (2001) found that overexpression of IL20 in transgenic
mice caused neonatal lethality with skin abnormalities, including
aberrant epidermal differentiation. Recombinant IL20 protein stimulated
a signal transduction pathway through STAT3 (102582) in a keratinocyte
cell line, demonstrating a direct action of this ligand. The authors
also identified an IL20 receptor, which exists as a heterodimer of 2
orphan class II cytokine receptor subunits, IL20RA (605620) and IL20RB
(605621). Both receptor subunits were expressed in skin and were
dramatically upregulated in psoriatic skin. Blumberg et al. (2001)
concluded that IL20 is involved in epidermal function and psoriasis

*****

These last two links went with something posted a few days back. And i
can't
find it. :(

Or can I?

Was it this?
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_frm/thread/bac0ec6d532d9f6c/1dbb811182e152ef#1dbb811182e152ef

randall... hate when that haPPens.

randall

unread,

Nov 10, 2005, 4:22:58 PM11/10/05

randall wrote:

> Now add this one to it,

http://www.signonsandiego.com/uniontrib/20051005/news_1c05brain.html

I went back and read this a second and third time.

MEDICINE
Gut feelings: System acts as second brain

By Harriet Brown
NEW YORK TIMES NEWS SERVICE

October 5, 2005

Two brains are better than one. At least that is the rationale for the
close - sometimes too close - relationship between the human body's
two brains, the one at the top of the spinal cord and the hidden but
powerful brain in the gut known as the enteric nervous system.

(Some primitive male friends of mine would argue for another head
further south even!
Are three brains better then two? )

For Dr. Michael D. Gershon, the author of "The Second Brain" and the
chairman of the department of anatomy and cell biology at Columbia, the
connection between the two can be unpleasantly clear. "Every time I
call the National Institutes of Health to check on a grant proposal,"
Gershon said, "I become painfully aware of the influence the brain has
on the gut."

(Do you think someone can really think their way to sick to the
stomach? But does
that also include those with gut:: reality problems leading to physical
dis-ease?)

In fact, anyone who has ever felt butterflies in the stomach before
giving a speech, a gut feeling that flies in the face of fact or a bout
of intestinal urgency before an examination has experienced the actions
of the dual nervous systems.

(Does craPPing your pants or craPPing your skin really haPPen due to
thinking? If
so we can all remedy our P by being stuPiP? Or just quit thinking? )

The connection between the brains lies at the heart of many woes,
physical and psychiatric. Ailments like anxiety, depression, irritable
bowel syndrome, ulcers and Parkinson's disease manifest symptoms at the
brain and the gut level.

"The majority of patients with anxiety and depression will also have
alterations of their GI function," said Dr. Emeran Mayer, professor of
medicine, physiology and psychiatry at UCLA.

A study in 1902 showed changes in the movement of food through the
gastrointestinal tract in cats confronted by growling dogs.

(How about barking spiders?)

One system's symptoms - and cures - may affect the other.
Antidepressants, for example, cause gastric distress in up to a quarter
of the people who take them. Butterflies in the stomach are caused by a
surge of stress hormones released in a "fight or flight" situation.
Stress can also overstimulate nerves in the esophagus, causing a
feeling of choking.

(hpa stress? Ok,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=hpa&qt_g=1&searchnow=Search+this+group
And some of us have been successful with ssri's,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=ssri%27s&qt_g=1&searchnow=Search+this+group
What is a ssri?
http://www.antidepressantsfacts.com/taper.htm
Selective Serotonin Reuptake Inhibitors (SSRI's) have to be used under
the direction
of a doctor. So if you do clear your P, then you know serotonin uptake
is at stake.)

Gershon, who coined the term "second brain" in 1996, is one of a number
of researchers who are studying brain-gut connections in the relatively
new field of neurogastroenterology. New understandings of the way the
second brain works, and the interactions between the two, are helping
to treat disorders like constipation, ulcers and Hirschprung's disease.

(But can we control P with more serotonin? We know imagery and
meditation with drugs will clear one up to four times faster then
without them. )

Digestive brain

The role of the enteric nervous system is to manage every aspect of
digestion, from the esophagus to the stomach, small intestine and
colon. The second brain, or little brain, accomplishes all that with
the same tools as the big brain, a sophisticated, nearly self-contained
network of neural circuitry, neurotransmitters and proteins.

The independence is a function of the enteric nervous system's
complexity.

"Rather than Mother Nature's trying to pack 100 million neurons
someplace in the brain or spinal cord and then sending long connections
to the GI tract, the circuitry is right next to the systems that
require control," said Jackie D. Wood, professor of physiology, cell
biology and internal medicine at Ohio State.

Two brains may seem like the stuff of science fiction, but they make
literal and evolutionary sense.

"What brains do is control behavior," Wood said. "The brain in your gut
has stored within its neural networks a variety of behavioral programs,
like a library. The digestive state determines which program your gut
calls up from its library and runs."

When someone skips lunch, the gut is more or less silent. Eat a
pastrami sandwich, and contractions all along the small intestines mix
the food with enzymes and move it toward the lining for absorption to
begin. If the pastrami is rotten, reverse contractions will force it
- and everything else in the gut - into the stomach and back out
through the esophagus.

In each situation, the gut must assess conditions, decide on a course
of action and initiate a reflex.

"The gut monitors pressure," Gershon said. "It monitors the progress of
digestion. It detects nutrients, and it measures acid and salts. It's a
little chemical lab."

The enteric system does this on its own, with little help from the
central nervous system.

GI disorders

It is no surprise that there is a direct relationship between emotional
stress and physical distress. "Clinicians are finally acknowledging
that a lot of dysfunction in GI disorders involves changes in the
central nervous system," said Gary M. Mawe, a professor of anatomy and
neurobiology at the University of Vermont.

(My main question now comes down to whether the gut permeability is
raised in these
gutty situations? Can you have a leaky gut due to thinking? Now that
would raise my
P levels)

The big question is which comes first, physiology or psychology?

(Is this a chicken or egg question? lol)

The enteric and central nervous systems use the same hardware, as it
were, to run two very different programs. Serotonin, for instance, is
crucial to feelings of well-being. Hence the success of the
antidepressants known as SSRIs that raise the level of serotonin
available to the brain.

(SSRi's ok we know about them already for P. )

But 95 percent of the body's serotonin is housed in the gut, where it
acts as a neurotransmitter and a signaling mechanism. The digestive
process begins when a specialized cell, an enterochromaffin, squirts
serotonin into the wall of the gut, which has at least seven types of
serotonin receptors. The receptors, in turn, communicate with nerve
cells to start digestive enzymes flowing or to start things moving
through the intestines.

( NOw this raises the question about which funky bug or commensals
influence the
gut walls and thereby influence STATs and ultimately inflammation.
STAT-
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=stat&qt_g=1&searchnow=Search+this+group
Does stat3 get jiggered by the gut flora? I'd tend to think so! WhooPs
can't help it.

Damn, I can't stoP thinking!!! Yikes! )

Serotonin also acts as a go-between, keeping the brain in the skull up
to date with what is happening in the brain below. Such communication
is mostly one way, with 90 percent traveling from the gut to the head.

(And then to the skin? )

Many of those messages are unpleasant, and serotonin is involved in
sending them. Chemotherapy drugs like doxorubicin, which is used to
treat breast cancer, cause serotonin to be released in the gut, leading
to nausea and vomiting.

( serotonin must be somewhere in these pathways for P,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=serotonin&qt_g=1&searchnow=Search+this+group
Or maybe it's just a bit player? )

Serotonin is also implicated in one of the most debilitating gut
disorders, irritable bowel syndrome, or IBS, which causes abdominal
pain and cramping, bloating and, in some patients, alternating diarrhea
and constipation.

(IBS, is in the pathways for some of us,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=ibs&qt_g=1&searchnow=Search+this+group
As well as crohn's and other gut problems )

The default assumption has been that the syndrome is a psychosomatic
disease. But it turns out that irritable bowel syndrome, like
depression, is at least in part a function of changes in the serotonin
system. In this case, it is too much serotonin rather than too little.

In a healthy person, after serotonin is released into the gut and
initiates an intestinal reflex, it is whisked out of the bowel by a
molecule known as the serotonin transporter, or SERT, found in the
cells that line the gut wall.

People with irritable bowel syndrome do not have enough SERT, so they
wind up with too much serotonin floating around, causing diarrhea.

The excess serotonin then overwhelms the receptors in the gut, shutting
them down and causing constipation.

(on this end of the teetertotter we have diarrhea and constipation on
the other with
serotonin in the middle. Where does the p figure in? )

When Gershon, whose work has been supported by Novartis, studied mice
without SERT, he found that they developed a condition very much like
IBS in humans.

Several new serotonin-based drugs - intestinal antidepressants, in a
way - have brought hope for those with chronic gut disorders
>
> Then add in my gut feelings.
>
> Is P somewhere in this gutter? lol
>
> Could we have a gut brain iron permeable gut LPS gene thing?
>
> I need to rePhrase that last inquiry. <g>
>
> Does our uPstair brain screw with the gut brain and make more p?
>
>
> > High cortisol levels will impair entry of amino acids into muscle cells.
>
>
> So thats why i had such a hard time bulking up for high school
> football?
>
> Darn, i may have used roids if they had been around back then.
>
> On second thought good thing they weren't. I'm not so sure that P and
> roid rage go to-gether any better then P and anything.
>
>
> <sniP>
> >

>
> Sorry. Couldn't resist once again.
>
> randall my gut feelings are still there. Butterflies or 2 much
> thinking?
> >

Ok. Wait a minute.

I know what your thinking. I thinking about your thinking now! Wow!

OK, lets find anything in the gut for P that won't Piss OFF the skin.

Almost all about citrulline in mammals.

Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Benazeth S,
Cynober L.

Laboratoire de Biomathematiques, E.A. 2498, Faculte de Pharmacie,
Universite Rene Descartes, Paris, France.

PMID: 16082501

Could we Pee out the P factors somehow?

Now that wouldn't urea me off?

randall.. it would make me haPPy.

randall

unread,

Nov 20, 2005, 2:33:06 PM11/20/05

Hi,

P news from around the world.

But not today. Reading it and the pubmed site left me
speechless and Contemplative of my own situation yes.

Yet the news was a general bust as to curing and answering the big P
questions.

Cept for these on pubmed.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16285288
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16288306

Which both made me think. Treating it systemic versus it just being in
the skin and near terrain.

Don't let them strain your brain.

Since P is multifactorial they both can be right.

The genes (C-jun and junB) can and do act right in the skin,
http://groups.google.com/groups?q=junb+c-jun+psoriasis&qt_s=Search

So?

Well!

How come all the skin doesn't Plaque out then?

Could it be due to the severity of inflammation that resides systemic
wide?

Of course it does. My P responds to the seasons like the moon rules
the tide.

And,

I can easily eat and drink my way to severe psoriasis in short order.

But I prefer to eat and drink my way to mild psoriasis.

Can you think or meditate to less P?

Yes and many studies have shown that imagery with known treatments may
even shorten the duration of healing by 75%.

So. Whats behind this?

Genes?

But just in the skin or systemic wide?

This link shows inflammatory genes that cascade in CHD and are
very similar to those that help cascade P.

http://www.sciencedaily.com/releases/2005/11/051114220644.htm

<snip>
Specifically, the deleterious polymorphisms were in genes that code
for the production of four different proteins: interleukin-6 (IL-6),
C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM1) and
lipopolysaccharide-binding protein (LBP).

IL-6 is a protein that regulates the intensity of the immune response,
and CRP is a protein released into the bloodstream as a natural
reaction to infection, fever or other injury. ICAM-1 allows the white
cells to attach to the inner lining of the blood vessels where they
inflict damage. LBP regulates the body's response to bacteria normally
living in the gastrointestinal tract that can release endotoxins into
the bloodstream as a result of the action of the heart-lung machine.

The final polymorphism -- in a gene that codes for the enzyme catalase
-- appears to be involved in mediating the effects of oxidative stress.
The normal version of the gene produces proteins that can blunt the
negative effects of oxygen free radicals, while the polymorphism is
unable to do so effectively. It is well established that heart muscle
cells are placed under oxidative stress during reperfusion. <sniP>

The bod knows how to heal itself. Despite the need to have a doctor fix
what you
forked up. Yet in a small percentage of folks inflammatory genes
cascade and the
immune factors can not be overlooked.

Why else are we in the 2% club?

I think that LPS and LBP in the gut make a huge difference. How they
react with P and in what order I don't have a handle on.

*****************

Let's now look at feeding your face to change your gene's.

We use a mouse model for skin and here's one for food/genes.

http://www.newscientist.com/channel/health/mg18825264.800

<sniP>

Two years ago, researchers led by Randy Jirtle of Duke University
Medical Center in Durham, North Carolina, showed that the activity of a
mouse's genes can be influenced by food supplements eaten by its mother
just prior to, or during, very early pregnancy (New Scientist, 9 August
2003, p 14). Then last year, Moshe Szyf, Michael Meaney and colleagues
at McGill University in Montreal, Canada, showed that mothers could
influence the way a rat's genes are expressed after it has been born.
If a rat is not licked, groomed and nursed enough by its mother,
chemical tags known as methyl groups are added to the DNA of a
particular gene.

The affected gene codes for the glucocorticoid receptor gene, expressed
in the hippocampus of the brain. The gene helps mediate the animal's
response to stress, and in poorly raised rats, the methylation damped
down the gene's activity. Such pups produced higher levels of stress
hormones and were less confident exploring new environments. The effect
lasted for life (Nature Neuroscience, vol 7, p 847).

Now the team has shown that a food supplement can have the same effect
on well-reared rats at 90 days old - well into adulthood. The
researchers injected L-methionine, a common amino acid and food
supplement, into the brains of well-reared rats. The amino acid
methylated the glucocorticoid gene, and the animals' behaviour changed.
"They were almost exactly like the poorly raised group," says Szyf, who
announced his findings at a small meeting on environmental epigenomics
earlier this month in Durham, North Carolina.
"This opens up new ways of thinking about treating and preventing
diseases caused by how our DNA is expressed"

Though the experiment impaired well-adjusted animals, the opposite
should be possible, and Szyf has already shown that a chemical called
TSA that is designed to strip away methyl groups can turn a badly
raised rat into a more normal one.

No one is envisaging injecting supplements into people's brains, but
Szyf says his study shows how important subtle nutrients and
supplements can be. "Food has a dramatic effect," he says. "But it can
go both ways," he cautions. Methionine, for instance, the supplement he
used to make healthy rats stressed, is widely available in capsule form
online or in health-food stores - and the molecules are small enough to
get into the brain via the bloodstream.

Rob Waterland from Baylor College of Medicine in Houston, Texas, who
attended the meeting, says Szyf's ideas are creating a buzz, as they
suggest that methylation can influence our DNA well into adulthood. A
huge number of diseases are caused by changes to how our DNA is
expressed, and this opens up new ways of thinking about how to prevent
and treat them, he says.

But Waterland points out there is still much work to be done.
Substances like methionine and TSA are, he says, a "sledgehammer
approach", in that they are likely to demethylate lots of genes, and we
don't even know which they will affect. But he speculates that
techniques such as "RNA-directed DNA methylation", so far tested only
in plants but theoretically possible in mammals, may allow us to target
such methylation much more precisely.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

While on the toPic of mice and genes. Mice and men and
Of MICE and Stathmin,
http://news.bbc.co.uk/1/hi/health/4449226.stm
One gene deleted and they know NO fear!

Did Willard feed his hoard the right Rx to breed a killer bunch? LOL

And can you eat to less hoary skin? Or is the reverse true?
It's only taken me a lifetime to prove that one.

Certainly anything bad for your system may kill a fetus or
distort the genes.

To heed or heal is that the Rx,
http://news.google.com/news?hl=en&tab=gn&ie=UTF-8&scoring=d&q=psoriasis+heeding&btnG=Search+News

***********

And what does the above mean?

It means something different for you then me.

What do I take?

And what does it do?

I like to think that i think right for starters.
And eat right for seconds.

And then suPPlement right to top off the ability to live right and with
less stress.

I feel in my gut that the best of the best supplements.

Are first and foremost taking care of the good flora in the colon.
To do that I take proflora whey powder nearly every day.
www.thewholewhey.com/contents/products_info/proflora.htm $18.50 for
2.75 lb (1249 g).

I take it with protein whey in a delicious smoothie that changes with
the seasons.

With that shake I take once a day the following supplements.

(OH WAIT! First thing in the morning i take one cap of IP6, inositol
hexaphosphate- 500 mgs and then don't eat or drink my shake for at
least one hour. Water and IP6 and then
wait. )

BACK to the shake and supplements.

I take 3 grams of vitamin C.
600 mg.s of NAC (n-acetyl cysteine) one a day, rarely twice a day
depending on
cheat eating.
175 mg.s of milk Thistle
Glucosamine HCL 1500 mg/ Chondroitin Sulfate 1200 mg.s - 2 tabs costco
brand
split with two meals. But most days i forget to take the second one at
dinner.
160 mg.s of saw plametto. up to three a day taken one time.
500 mg.s of ascorbyl plamitate every other day or so.
100 mg.s of alpha lipoic acid once a day
1000 mg caps of fish oil- costco brand, take two a day in the am.
CoQ10 - 50-100 mg.s a day

>From melaleuca (the last seven months will be stopping them soon and
switch brands)

One multivitamin/mineral called: Vitality for men
Also once a day at night: Vitality Mineral complex with calcium.
Phytomega (omega -3's & Phytosterols) one a day with fish caps in the
am.
Provex plus (anitoxidant complex)
Provex CV (cardio vascular formula) two a day

Taken at night mostly if I remember:
Homocysteine formula: B-6, B-12, and folic acid
Magnessium 250 mg.s (once or twice a day depending on regularity)
Selenium 200 mcg.s taken at supper time once a day.

Taken before bed if needed (hasn't been for some reason. I do love this
stuff)
Melatonin 1 mg has B-6 and some calcium. Take 1-3 tablets.

With my shake in the mornings i take a half tablespoon of flax seed
oil.
Use to take a tablespoon of cod liver oil, but have switched to the
fish caps from costco.

*************
I would also figure my main diet is wholesome and supplies many if not
most
of the nutrients, proteins, and carbs needed to live an average
stressful life.
I add ginger and curcumin and other herbs to my shakes as well as
frozen
grapes, bananas and other fruits to numerous to mention.

***********

At this time i'm staying under 3% Pasi.

I'm happy and I can cheat eat to the point that i feel like a pig.

So, i back off and thank god that I feel and look good.

Am I forgetting somethings?

Most likely

Honestly? Well exercise has taken a back burner due to work for the
last seven
months. Almost zero of that. I do Qi Gong once a week in a class
situation.

I should get back to walking on a daily basis. And will when i do.

I also forgot those foods like omega-6's that i try to avoid except for
the
ones that come with the omega-3's in the flax oils.

Oils and fats are huge otherwise and i go to lengths to keep a
beneficial ratio.

I could write 50 times more then this little article as to what I eat
or don't eat.

But not now. It took me a week to get around to doing this and i was
suPPose
to have done it a week ago. lol

randall... be well and the hell with the rest, but don't forget to
rest.

randall

unread,

Nov 22, 2005, 2:26:43 PM11/22/05

Hi,

P news from around the world.

Before we get going.

Just a short piece to juxtapose for those Peta people out there.

"All beings hitherto have created something beyond themselves: and ye
want to be the ebb of that great tide, and would rather go back to the
beast than surpass man?
What is the ape to man? A laughing-stock, a thing of shame. And just
the same shall man be to the Superman: a laughing-stock, a thing of
shame.
Ye have made your way from the worm to man, and much within you is
still worm. Once were ye apes, and even yet man is more of an ape than
any of the apes. "
(from Thus Spoke Zarathustra) Friedrich Nietzsche

Somewhere between Nietzsche and Darwin lies an answer.

Green or black tea?

Can black tea theaflavins slow inflammation?
http://www.foodnavigator-usa.com/news/ng.asp?n=64014-wellgen-nutrigenomics-theaflavins-black-tea
(...)
One of the most exciting new areas in food and wellness, nutrigenomics
involves working out which chemicals in foods have the ability to turn
on and off certain genes that are responsible for disease prevention.

******

Yeah and don't eat soybean oil (n6) if your on fire to begin with.

Sorry almost did the rant. This post is for the little animals and
those
with P dna.

Back to more serious notions.

Before you swat your next fly parse this one.

Fruit flies reveal MTX pathways,
http://www.sciencedaily.com/releases/2005/11/051122093217.htm

"There is a tremendous amount of study to be done of mice and men,"
says John Steinbeck,

http://www.clipartxp.com/Cartoons/Mighty_mouse2.jpg

Humanized mice : are we there yet?
http://www.jem.org/cgi/content/full/202/10/1307
<sniP>
Autoimmunity
HLA-transgenic mice are particularly useful in modeling human
autoimmune diseases that are associated with specific HLA alleles.
HLA-transgenic mouse models have been established for rheumatoid
arthritis, relapsing polychondritis, experimental autoimmune
encephalomyelitis, celiac disease, and Type 1 diabetes (21). These mice
offer advantages over many other experimental models as they more
closely reflect human pathologies. For example, HLA-DQ8 transgenic mice
have rheumatoid factor, an antibody typically expressed only in
rheumatoid arthritis patients, whereas this marker is absent in other
animal models of this disease. And the NOD.HLA-DQ8 model of celiac
disease is unique in presenting with dermatitis herpetiformis, a
chronic and extremely itchy rash which is a predominant pathological
feature of the human disease.
The classical mouse models of autoimmune skin diseases are inadequate
because of their complex pathophysiology and the marked differences
between human and mouse skin-associated immunity, a major limitation
being that experimental mouse skin reactions are primarily acute,
whereas the human diseases are mostly chronic. Thomas Zollner
(Richmond, CA) presented data showing that psoriasis could be induced
by injection of bacterial superantigens or autologous T cells into
nonlesional skin grafts taken from psoriasis patients and grafted onto
SCID mice or onto SCID mice that are also homozygous for the beige
(Lystbg or bg) mutation (scid/bg mice) (22), which results in lowered
NK cell activity. The ensuing dermatitis resembled human psoriasis in
key features such as excessive skin growth, and thickening and scaling
of the skin accompanied by T cell expansion, keratinocyte
hyperproliferation, and focal ICAM-1 expression. Furthermore, all
antipsoriatic compounds currently used to treat humans were effective
in treating dermatitis in scid/bg mice. Efficacy testing in this model
should allow selection of the best new drug candidates for clinical
studies
<sniP>

http://www.online.ie/News/News.aspx?newsId=130008
Eat worms to cure P?
(...)
Researchers at Trinity College Dublin have discovered eggs from a
parasitic worm, Schistosoma mansoni, may aid in the treatment of
inflammatory conditions such as psoriasis.

The worm, which infects humans, releases molecules with strong
anti-inflammatory qualities effective in battling against acute
inflammations.

"This study is particularly exciting as it harnesses how the worm
modifies immunity in our bodies to stimulate protection from
undesirable inflammation," Dr Padraic Fallon, School of Biochemistry
and Immunology, TCD, who led the project, said.
(...)

What is the relationship of dna to man and mouse?

http://groups.google.com/groups?hl=en&lr=&q=dna+mouse++man+worm+fugu+fish&qt_s=Search

Would a worm, fly or mouse drink alcohol?

Could Superman hold his liquor better then a bottle. Should he?

What makes us think we can drink without the skin revealing the brains
quest for endorphins?
http://www.dailymail.co.uk/pages/live/articles/health/dietfitness.html?in_article_id=316935&in_page_id=1798
(...)
The skin condition psoriasis, which leads to red scaly patches over the
body, can be another side effect of heavy drinking - 40% of psoriasis
sufferers drink too much.
(...)

*****

We all want to feel good without getting hooked on smack.

How to have moist skin the jackson hole way.
http://www.jacksonholestartrib.com/articles/2005/11/22/features/health/cb0263981c4bb07d872570c0005d6780.txt

Don't let winter get under your skin

Anyone who's endured a Wyoming winter knows those long, cold months
tend to get under people's skin emotionally. As it turns out, winter
can also physically get under your skin.

Winter conditions are notoriously hard on the skin. The wind sometimes
blows for days, mercilessly buffeting exposed parts whenever we go
outside.

The outside air sometimes seems dry enough to suck water out of a
sponge. Inside air can be even drier.

All those conditions, and the lack of humidity in particular, often
gang up to cause an exotic sounding malady called xerotic dermatitis,
commonly known as dry skin.
Dr. Scott Bennion, of Medical Skin Care in Casper, said dry skin is the
most common complaint dermatologists see in the winter.

"It's a physics thing," said Bennion. "Anything less than 60 percent
humidity in the air your skin obligatorily loses water to the
atmosphere. ... Inside in the winter, where most people are, the
humidity is usually 20 percent or less. ... That's the main reason
people have problems with dry skin in the wintertime."

Dry skin manifests itself as a rash, or cracked and scaly skin. It is
often accompanied by an annoying persistent itch, which can feel like
winter literally is under your skin.

But winter skin problems aren't limited to xerotic dermatitis.
<sniP>

******

Jude Law going bald? Can homeopathy save it?
http://www.telegraph.co.uk/health/main.jhtml?view=DETAILS&grid=P8&xml=/health/2005/11/21/hbald21.xml
(...)
He is not alone. Research from the University of Wales found that the
prospect of baldness causes at least as much anguish in men as a
serious skin condition, such as psoriasis. "Baldness causes men far
more suffering than I had ever imagined,"
(...)

^^^^^^^^^^^^^^

Abstract time:::

[Immunopathogenesis of psoriasis]

[Article in German]

Ghoreschi K, Rocken M.

Universitats-Hautklinik, Eberhard Karls Universitat Tubingen.
Kamran.G...@med.uni-tuebingen.de

Psoriasis is a chronic inflammatory disease of the skin and the joints.
Multiple factors contribute to the initiation of psoriasis. They
include specific genetic characteristics such as major
histocompatibility antigens and psoriasis susceptibility genes, as well
as trigger factors, namely streptococcal infections. Today, psoriasis
is considered as a T-lymphocyte mediated autoimmune disease, even
though the ______________putative autoantigen_________ remains unknown.
Bacterial proteins with similarity to structural proteins of
keratinocytes are potential target antigens. As in other autoimmune
diseases, inflammatory cytokines of the innate immune system initiate a
cascade that activates inflammation locally in the skin, in the
circulation and most likely also in lymph nodes. IFN-gamma-producing
CD4+ Th1-lymphocytes seem to be of central importance in the
pathogenesis of psoriasis as they critically influence differentiation
and functioning of antigen presenting cells, mast cells, neutrophils
and endothelial cells. This inflammatory cascade simultaneously
provokes neoangiogenesis in the dermis and proliferation of
keratinocytes. Based on this hypothesis, cytokines or anticytokine
antibodies that either inhibit T-cell mediated inflammation or
transform disease-inducing, pro-inflammatory Th1-lymphocytes into a
phenotype with anti-inflammatory properties were tested in psoriasis.
As both approaches improved psoriasis, they strongly support the
current concept that views psoriasis as a Th1-lymphocyte mediated
disease.

PMID: 16295038

Increased Sensitivity to Interferon-alpha in Psoriatic T Cells.

Eriksen KW, Lovato P, Skov L, Krejsgaard T, Kaltoft K, Geisler C, Odum
N.

Institute of Molecular Biology and Physiology, Department of
Immunology, University of Copenhagen, Copenhagen, Denmark.

Psoriasis is a chronic inflammatory skin disease characterized by
abnormal epidermal proliferation. Several studies have shown that
skin-infiltrating activated T cells and cytokines play a pivotal role
during the initiation and maintenance of the disease. Interferon
(IFN)-alpha plays an important role in host defense against infections,
but recent data have also implicated IFN-alpha in psoriasis. Thus,
IFN-alpha induces or aggravates psoriasis in some patients, and mice
lacking a transcriptional attenuator of IFN-alpha/beta signaling
spontaneously develop a psoriasis-like inflammatory skin disease
characterized by CD8(+)-infiltrating T cells. In this study, we
therefore investigate IFN-alpha signaling in T cells isolated from
involved skin of psoriatic patients. We show that psoriatic T cells
have increased and prolonged responses to IFN-alpha, on the level of
signal transducers and activators of transcription (STAT) activation,
compared with infiltrating T cells from skin of non-psoriatic donors.
Functionally, the increased IFN-alpha signaling leads to an increased
binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and
inhibition of T cell growth. In contrast, to STAT responses to other
cytokines were not changed in psoriasis. In conclusion, we provide
evidence that psoriatic T cells have an increased sensitivity to
IFN-alpha. Thus, our data suggest that increased IFN-alpha signaling is
involved in the pathogenesis of psoriasis.

PMID: 16297193

Systematic Linkage Disequilibrium Analysis of SLC12A8 at PSORS5
Confirms a Role in Susceptibility to Psoriasis Vulgaris.

Huffmeier U, Lascorz J, Traupe H, Bohm B, Schurmeier-Horst F, Stander
M, Kelsch R, Baumann C, Kuster W, Burkhardt H, Reis A.

Institute of Human Genetics, University Erlangen-Nuremberg, Erlangen,
Germany.

The gene for solute carrier family 12 member A8 has recently been
proposed as a candidate gene for psoriasis susceptibility (PSORS5) on
chromosome 3q based on association of five single nucleotide
polymorphisms (SNP) in Swedish patients. To investigate whether this
locus is relevant for German psoriasis vulgaris (PsV) patients, we
analyzed a group of 210 trios and a case-control group including 375
patients. Based on our investigation of the linkage disequilibrium (LD)
structure of SLC12A8, we assayed 35 haplotype tag SNP and grouped them
into nine LD-blocks. In the case-control study, we detected an
association for six SNP and three LD-based haplotypes. Association was
strongest for ss35527511 (chi(2)=11.224, p=0.0008) and haplotype E-2
(chi(2)=11.788, p=0.00059) and independent of the presence of an
HLA-associated PSORS1 risk allele. Through extended haplotype analysis,
we could show that two independent association signals exist in
SLC12A8, suggesting allelic heterogeneity. None of the SNP showed
association in trios, apart from a weak association of rs2228674
(transmission disequilibrium test statistics p=0.048), probably due to
insufficient power. We conclude that SLC12A8 is a susceptibility locus
for PsV. In order to establish the exact nature of this association,
efforts to identify the disease-causing variants are ongoing.

PMID: 16297188

The Region of 150 kb Telometic to HLA-C Is Associated with Psoriasis in
the Jewish Population.

Martinez-Borra J, Brautbar C, Gonzalez S, Enk CD, Lopez-Vazquez A,
Lopez-Larrea C.

Department of Immunology, Hospital Universitario Central de Asturias,
Oviedo, Spain.

The HLA-Cw(*)0602 has been associated with psoriasis in different
ethnic groups. But, it remains unclear whether HLA-C is the PSORS1 gene
(the psoriasis gene in the MHC). Thus, several case-control studies
have been performed in order to investigate whether HLA-C itself
determines the susceptibility to the disease. We studied 59 Jewish
patients with type I psoriasis and 79 matched controls. Polymorphic
genes and markers from HLA-B (centromeric to HLA-C) to the
corneodesmosin (CDSN) gene (telomeric to HLA-C) were genotyped in order
to determine their contribution to the susceptibility to psoriasis.
Neither HLA-Cw(*)0602 nor the allele CDSN(*)TTC were significantly
associated with psoriasis with the size of the sample studied. The
genes and markers telomeric to HLA-C such as the microsatellite C1_4_4
(OR=2.6, 95% CI=1.4-4.7, p(c)=0.018) the octamer transcription factor
(OTF)-3 gene (OR=2.6, 95% CI=1.6-4.3, p(c)=0.0001) and the alpha-helix
coiled-coil rod homologue (HCR) gene (OR=2.5, 95% CI=1.3-4.5,
p(c)=0.004), however, were associated with the disease. These results
suggest that a major psoriasis susceptibility gene is likely to be
located within a region of 150 kb telomeric to HLA-C and centromeric to
the CDSN gene.

PMID: 16297191

Are you happy to see me or is that a banana in your pants?

http://groups.google.com/group/talk.origins/browse_frm/thread/1ad3cd97f1e6de37/64faa4173eaa06ff?lnk=st&q=dna+mouse++man+worm+fugu+fish&rnum=2&hl=en#64faa4173eaa06ff

Gosh, i'm only 20-30% sure.

randall... time for a smoothie with frozen banana's

randall

unread,

Nov 26, 2005, 3:28:45 PM11/26/05

Hi,

The P news was slow and or boring this week.

Abstracts are another story.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16307645
Response of the hypothalamic-pituitary-adrenal axis to psychological
stress in patients with psoriasis.

Richards HL, Ray DW, Kirby B, Mason D, Plant D, Main CJ, Fortune DG,
Griffiths CE.

The Dermatology Centre, The University of Manchester, Hope Hospital,
Salford, Manchester M6 8HD, U.K.

Summary Background Psoriasis may, in some patients, be triggered and/or
exacerbated by stress. Objectives As activation of the
hypothalamic-pituitary-adrenal (HPA) axis is critical to a successful
stress response we investigated this in patients with psoriasis.
Methods Forty patients with chronic plaque psoriasis and 40 age-matched
normal controls experienced three randomly presented acute
psychological stressors (cognitive, emotional and social). Serial serum
cortisol, pulse rate and blood pressure assessments were undertaken at
baseline and following each of the stressors. Salivary cortisol samples
were collected at 09.00 h on the day of testing. Results In control
subjects there was a significant (r = 0.38; P < 0.05) correlation
between pulse rate and serum cortisol level following the social
performance stressor; this was not evident in the psoriasis group (r =
0.07; not significant). Patients who believed that their psoriasis was
highly stress responsive had significantly lower salivary cortisol
levels at baseline (P < 0.01) and lower serum cortisol levels following
the social performance stressor (P = 0.016) than patients with
nonstress-responsive disease who believed that stress had no impact. In
contrast, there was no difference between the groups for change in
pulse rate poststressor. Conclusions This study shows that patients
with psoriasis, and in particular those whose disease appears to be
stress responsive, exhibit an altered HPA response to acute social
stress. The implication is that such patients may perhaps be primed to
flares of their psoriasis. Whether this is genetically predetermined
and/or a consequence of the distress of living with psoriasis remains
to be determined.

PMID: 16307645

Duh! What comes first the stress or the P genes?

Since only 2% of the poP has it. You'd think it was explanatory. Unless
what there
asking is how many of the 2% flare due to hpa-axis tiltings.

Ok. Lets see. It's late in the day melatonin is at a peak <wink wink>
and the
stress is building from work. You go home and remember to avoid the
liquid pressure
pills, cause randall said it may do something with your flares, and
out plops all the food on the table that you know will flare you. But
you don't
care, so you gobble it all up and have three martini's in the process
and then
wash it all down with grapefruit juice. Now you feel so guilty that the
stress is
hitting the toP of your head. It feels like it's gonna blow. You grab
some aspirin
and your wife left some lithium mixed in with it and you get a few of
those
as well.

Is it the stress, the genes or the oral combo? Or are the triggers
acting
on the genes or do they add to the hPa-axis stress curve?

Now try to devise a test of these if the stress isn't enough.

Or get a microscope and look at the neuts. Can they tell you whats
going down?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16301678
T cell-regulated neutrophilic inflammation in autoinflammatory
diseases.

Keller M, Spanou Z, Schaerli P, Britschgi M, Yawalkar N, Seitz M,
Villiger PM, Pichler WJ.

Division of Allergology, Clinic of Rheumatology and Clinical
Immunology/Allergology, Inselspital, University of Bern, Bern,
Switzerland;

Previous studies of acute generalized exanthematous pustulosis, a
peculiar drug hypersensitivity reaction, suggested that CXCL8-producing
T cells regulate sterile, polymorphonuclear neutrophil-rich skin
inflammations. In this study, we test the hypothesis of whether
CXCL8-producing T cells are present in autoinflammatory diseases like
pustular psoriasis and Behcet's disease. Immunohistochemistry of normal
skin revealed few CD4(+) and CD8(+) T cells, few CXCL8(+) cells, and no
neutrophilic infiltration, whereas in acute exacerbations of atopic
dermatitis, numerous CD4(+) T cells but few CD8(+) T cells,
neutrophils, or CXCL8(+) cells were detected. In contrast, a pronounced
infiltration of neutrophils and of predominantly CD4(+) T cells was
observed in skin biopsies from pustular psoriasis, Behcet's disease,
and acute generalized exanthematous pustulosis, with infiltrating T
cells strongly positive for CXCL8 and the chemokine receptor CCR6.
Skin-derived T cell clones from pustular skin reactions were positive
for CCR6 but negative for CCR8 and secreted high amounts of CXCL8 and
GM-CSF, often together with IFN-gamma and TNF-alpha after in vitro
stimulation. Moreover, some skin-derived T cell clones from Behcet's
disease and from pustular psoriasis predominantly produced CXCL8 and
GM-CSF, but failed to secrete IL-5 and IFN-gamma. These cells might
represent a particular subset as they differ from both Th1 as well as
Th2 T cells and are associated with a unique, neutrophil-rich sterile
inflammation. Our findings suggest that CXCL8/GM-CSF-producing T cells
may orchestrate neutrophil-rich pathologies of chronic autoinflammatory
diseases like pustular psoriasis and Behcet's disease.

PMID: 16301678

Cool. NOt th1 or th2. I wonder how they react in th1/th2 states of
being?

randall.. had a haPPy turkey day.. now thats stress. What king? don't
ask!

randall

unread,

Dec 1, 2005, 12:25:59 PM12/1/05

Hi,

P news from around the world and abstracts from pubmed.com

How about a study with this cocktail. K252a, BCX-4208 and VTP-201227.

Think i'm fooling? Read on.

*******

http://www.genengnews.com/news/bnitem.aspx?name=1117443XSL_NEWSML_TO_NEWSML_WEB.xml
Bio3 Research S.r.l., and Creabilis Therapeutics S.p.A. announced
agreements with Cephalon, Inc. to evaluate the research compound K252a
for its potential to topically treat psoriasis and for potential use in
the prevention and treatment of restenosis. Creabilis Therapeutics owns
patent applications covering K252a-based products for the treatment of
psoriasis.

(...)

About Creabilis Therapeutics S.p.A.

Creabilis Therapeutics S.p.A. is a privately owned drug-discovery and
development company, founded in 2003 and located in the Bioindustry
Park of Canavese, near Turin. The company's activity focuses mainly on
DNA-binding proteins, such as HMGB1, as pharmacological targets for
novel classes of inhibitors/antagonists to be developed as
therapeutics. This portfolio is complemented by selected projects in
related biochemical or clinical areas. Additional information on
Creabilis Therapeutics can be obtained from
www.creabilistherapeutics.com or by e-mail:
in...@creabilistherapeutics.com

About Bio3 Research s.r.l.

Bio3 Research s.r.l., an Italian company founded in 2001, has
headquarters in Milan and an office at the Bioindustry Park of Canavese
(Turin). Bio3 Research works with research institutions, individual
scientists and early-stage companies to identify, protect and exploit
commercially promising intellectual property in the life sciences. Such
assistance may include pre-clinical development and negotiation of
strategic industrial partnerships. Bio3 Research's activity focuses
mainly on the field of HMBG1-related cardiovascular disorders and use
of HMGB1 and its fragments in connective tissue regeneration. Other
fields of interest include skin and renal diseases. Additional
information on Bio3 Research can be obtained from www.bio3research.com
or by e-mail: info @bio3research.com

&&&&&&&&&&&&&&

http://today.reuters.com/investing/financeArticle.aspx?type=hotStocksNews&storyID=URI:urn:newsml:reuters.com:20051130:MTFH48923_2005-11-30_18-46-43_N30243655:1

(...)

The deal gives Roche a potential treatment that might eventually be
used against autoimmune diseases, including rheumatoid arthritis,
psoriasis and Crohn's disease.

Roche said the BioCryst compound, known as BCX-4208, which is in the
early stages of testing, is believed to have a potent ability to
modulate inflammation-causing T cells, which help the body determine
when to start immune responses and whether to accept or reject newly
transplanted organs.

Under the terms of the exclusive license, BioCryst will receive an
up-front payment of $25 million and a $5 million payment as a
reimbursement for supply of material during the first 24 months of the
collaboration.

^^^^^^^^^^^^^

http://www.pharmaceutical-business-review.com/article_news.asp?guid=DFEE3FD2-B55F-4925-92B1-DEDEF6E6B332
(...)

30 Nov 2005, 17:10 GMT - The first phase II clinical compound,
VTP-201227, has a novel mechanism of action and is being developed as a
topical agent for the treatment of psoriasis with potential extensions
into other dermatological indications. The phase II trial is designed
to include 128 psoriasis patients at 16 study sites in the US.

VTP-201227 is a potent, selective inhibitor of two specific enzymes
that are active in the skin. Therapeutic targeting of these enzymes by
VTP-201227 promotes naturally-occurring healing processes within the
skin. The compound has been designed to be rapidly inactivated in
systemic circulation and thus has the potential to have a more
favorable safety profile. In preclinical animal models, VTP-201227 was
shown to exhibit a superior therapeutic index compared to other topical
dermatology drugs.

The second phase II clinical compound, VTP-195183, is being studied in
combination with other therapies for its potential to boost the levels
of infection-fighting white blood cells in certain oncologic
conditions. Vitae advanced the clinical program for this compound and
initiated a phase II clinical trial in October.

VTP-195183 is a novel subtype-specific nuclear receptor agonist that
has been shown to be generally safe and well tolerated in cancer
patients in phase I studies. The phase II clinical trial of VTP-195183
is being conducted outside of the US.

****************

A P cocktail you don't want to get.

(to obtain the related abstracts on these go to pubmed.com and enter
the PMID #)

A liver fibrosis cocktail? Psoriasis, methotrexate and genetic
hemochromatosis.

Mathew J, Morley N, Leong MY, Burt AD.

BACKGROUND: Pathologists are often faced with the dilemma of whether to
recommend continuation of methotrexate therapy for psoriasis within the
context of an existing pro-fibrogenic risk factor, in this instance,
patients with genetic hemochromatosis. Case Presentations We describe
our experience with two male psoriatic patients (A and B) on long term
methotrexate therapy (cumulative dose A=1.56 gms and B=7.88 gms) with
hetero- (A) and homozygous (B) genetic hemochromatosis. These patients
liver function were monitored with routine biochemical profiling; apart
from mild perivenular fibrosis in one patient (B), significant liver
fibrosis was not identified in either patient with multiple interval
percutaneous liver biopsies; in the latter instance this patient (B)
had an additional risk factor of partiality to alcohol. CONCLUSION: We
conclude that methotrexate therapy is relatively safe in patients with
genetic hemochromatosis, with no other risk factor, but caution that
the risk of fibrosis be monitored, preferably by non-invasive
techniques, or by liver biopsy.

PMID: 16316460

And the P gene info keeps coming in.

Human leukocyte antigens as psoriasis inheritance and susceptibility
markers.

Szczerkowska-Dobosz A.

Dermatology Department, Medical University of Gdansk, Poland.

Psoriasis is a multifactoral and heterogenetically inherited disease.
The role of hereditary transmission is supported by familial
association, twin studies, and correlation with human leukocyte
antigens (HLA). Numerous studies have proved that B13, B17, Cw6, and
DR7 antigens are positively associated with psoriasis. Cw6 antigen has
been repeatedly indicated to be the most significant marker for the
risk prediction of the disease. On the basis of epidemiological studies
and HLA analysis, a concept of two distinct disease patterns of
psoriasis vulgaris was proposed. In type I psoriasis the disease has an
early onset, strong correlation with Cw6, B13, B17, and DR7 antigens,
and familiar inheritance. Type II psoriasis has a late onset, weak
correlation with HLA antigens, and sporadic familiar occurrence. Both
types seem to differ clinically. Moreover, some extended haplotypes
were shown to be correlated with the disease, especially with the type
I psoriasis. Although a psoriasis susceptibility gene(s) has not been
yet identified, a number of candidate genes were studied, with evidence
for a major locus located within the major histocompatibility complex
(PSORS 1). Cw6 allele is the most extensively investigated candidate
gene, but present evidence suggests that it is rather in strong linkage
disequilibrium with the PSORS 1 gene than the susceptibility allele
itself. This article reviews past and current data on the genetic
background of psoriasis with special attention to its correlation with
HLA antigens.

PMID: 16314826

And from the same lab as the above,
HLA-C locus alleles distribution in patients from northern Poland with
psoriatic arthritis - preliminary report.

Szczerkowska Dobosz A, Rebala K, Szczerkowska Z, Nedoszytko B.

Department of Dermatology, Medical University, Gdansk, Poland.

The aim of the study was to compare the frequency of human leucocyte
antigen-C (HLA-C) locus alleles in patients with psoriatic arthritis
and in healthy controls in the same ethnic group in Poland, and to
correlate them with age of onset of psoriatic skin changes and joints
symptoms. HLA-C locus alleles of 41 patients and 80 controls were
determined by a polymerase chain reaction (PCR) low-resolution method.
The Cw*06 allele occurred more frequently (P adjusted for multiple
comparison = 0.004) in patients with psoriatic arthritis than in
controls. Patients who carried the HLA-Cw*06 allele had a significantly
earlier mean age of onset of both psoriasis (P = 0.01) and arthritis (P
= 0.008) compared with Cw*06-negative patients. Our results confirm the
association between Cw*06 allele and psoriatic arthritis in the
northern Poland population and suggest that the HLA-Cw*06 may determine
not only the disease susceptibility, but also the age of onset of
psoriatic arthritis.

PMID: 16313304

More good old chinese stuff (herbs?)

[Therapeutic efficacy of lixue xiaoyin decoction in treating psoriasis
and its effect on plasma edothelin]

[Article in Chinese]

Zhou M, Tao LC.

Department of Dermatology, Ruikang Hospital, Guangxi College of TCM,
Nanning 530011. zhoum...@163.com

OBJECTIVE: To study the therapeutic efficacy of Lixue Xiaoyin Decoction
(LXD) in treating psoriasis and its effect on plasma endothelin (ET).
METHODS: Two hundred and twenty patients were divided into two groups.
LXD was taken orally by the 118 patients in the treated group, while
Compound Qingdai Capsule (CQC) taken orally by the 102 patients in the
control group. The therapeutic efficacy was evaluated after 8 weeks of
treatment. The ET content was determined by radioimmunoassay before and
after treatment. RESULTS: The total effective rate was 73.72% in the
treated group and 54.90% in the control group with significant
difference (chi2 = 8.52, P < 0.01). The plasm ET level in patients was
significantly higher than that in the healthy subjects. ET in both
groups was all lowered after treatment, but the decrement was more
obvious in the treated group, showing significant difference when
compared with that in the control group (P < 0.01). CONCLUSION: LXD
shows good therapeutic efficacy in the treatment of psoriasis. It can
improve the microcirculation, inhibit the division of epithelial cells,
promote the epidermic cell differentiation, and shows regulative effect
on plasma ET.

PMID: 16313120

Funky skin or funky fetus?

Effect of thalidomide affecting VEGF secretion, cell migration,
adhesion and capillary tube formation of human endothelial EA.hy 926
cells.

Komorowski J, Jerczynska H, Siejka A, Baranska P, Lawnicka H, Pawlowska
Z, Stepien H.

Department of Clinical Endocrinology, Chair of Endocrinology, Medical
University of Lodz Dr Sterling 3 Street, 91-425 Lodz, Poland.

Angiogenesis, new blood vessel formation, is a multistep process,
precisely regulated by pro-angiogenic cytokines, which stimulate
endothelial cells to migrate, proliferate and differentiate to form new
capillary microvessels. Excessive vascular development and blood vessel
remodeling appears in psoriasis, rheumatoid arthritis, diabetic
retinopathy and solid tumors formation. Thalidomide
[alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor
of angiogenesis, but the mechanism of its inhibitory action remains
unclear. The aim of the study was to investigate the potential
influence of thalidomide on the several steps of angiogenesis, using in
vitro models. We have evaluated the effect of thalidomide on VEGF
secretion, cell migration, adhesion as well as in capillary formation
of human endothelial cell line EA.hy 926. Thalidomide at the
concentrations of 0.01 muM and 10 muM inhibited VEGF secretion into
supernatants, decreased the number of formed capillary tubes and
increased cell adhesion to collagen. Administration of thalidomide at
the concentration of 0.01 muM increased cell migration, while at 10
muM, it decreased cell migration. Thalidomide in concentrations from
0.1 muM to 10 muM did not change cell proliferation of 72-h cell
cultures. We conclude that anti-angiogenic action of thalidomide is due
to direct inhibitory action on VEGF secretion and capillary microvessel
formation as well as immunomodulatory influence on EA.hy 926 cells
migration and adhesion.

PMID: 16310808

*********

And the beat goes on.

randall... still looking pretty good for the time of year!

randall

unread,

Dec 8, 2005, 10:54:04 PM12/8/05

Hi,

P news from around the world.

Here it is,
http://news.google.com/news?lnk=li&tab=gn&q=psoriasis&ie=UTF-8&scoring=d&sa=N&start=10

Enough to bore one to death.

I saw this on the life extension newsgroup yesterday,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16311347
(...)
Expression of CD1d in human scalp skin and hair follicles: hair cycle
related alterations.

Adley MA, Assaf HA, Hussein M.

Department of Zoology, Sohag Faculty of Science, South Valley
University, Sohage, 44106 Egypt.

BACKGROUND: CD1d belongs to a family of antigen presenting molecules
that are structurally and distantly related to the classic major
histocompatibility complex class I (MHC I) proteins. However, unlike
MHC I molecules, which bind protein antigens, CD1d binds to lipid and
glycolipid antigens. CD1d is expressed by cells of lymphoid and myeloid
origin, and by cells outside of the lymphoid and myeloid lineages, such
as human keratinocytes of psoriatic skin.
<sniP>

So I thought, h'mmmm?

Time to check CD1d against the groups.
Thus,
http://groups.google.com/groups?q=cd1d+psoriasis&qt_s=Search

Now read this link. Eating carbs does have DNA ramifications
downstream.

http://www.scripps.edu/newsandviews/e_20050509/wong.html
(...)
He would speak about carbohydrate synthesis, carbohydrate arrays, and
how protein glycosylation (the attachment of carbohydrates to proteins)
is the most important type of post-translational modification that we
know of. Wong is one of the pioneers the field of oligosaccharide
synthesis-the production of the type of complex sugars (or
carbohydrates) that are commonly found attached to proteins and fat
molecules in the human body. Wong has spent years designing systems for
the synthesis of oligosaccharides and evaluating how these sugars are
involved in interactions relevant to health and disease.
(...)
http://www.scripps.edu/newsandviews/e_20050509/enlarge2.html
(...)
Carbohydrate structures are part of the language of life. They are like
the accents on spoken words-they change the meaning without changing
the spelling. Some even call carbohydrates the third alphabet, behind
DNA and proteins. Though they are not charged with storing genetic
information like DNA or acting as enzymatic workhorses like proteins,
carbohydrates nevertheless do carry information and are responsible for
important biological functions, playing a central role in many types of
intercellular communication events, particularly in the immune
system-roles that make many carbohydrates attractive targets for drug
design.

(...)

The lion's share of such drug research has involved the interactions of
small molecules with proteins or nucleic acids. Carbohydrate
recognition, which surely has important biological activity given the
volume of carbohydrates in the body, has lagged behind the fields of
protein and nucleic acid recognition. One of the main problems is that
carbohydrates are often so complex that they are among the most
difficult molecules for organic chemists to synthesize. The work that
Wong has done throughout his career is helping to change that.

More than fifty percent of the proteins in the human body are
glycosylated, Wong says to the crowd gathered in one of the conference
center's massive ballrooms. Most cells are covered with glycosylated
proteins many of which have unknown functions. "[Finding] the
functional aspects of carbohydrates is going to be the future," Wong
says.

A few days after the symposium, I got an email from the journal Nature
indicating that it was about to publish a paper on which Wong was a
coauthor with a team of researchers including Mitchell Kronenberg and
his group at the La Jolla Institute for Allergy and Immunology and
David Ho at the Aaron Diamond AIDS Research Center and New York
University. A few weeks earlier, another paper had come out by the same
team in the Proceedings of the National Academy of Sciences. Kronenberg
was the corresponding author on the former paper, and Wong was the
corresponding author on the latter.

The research was on an important type of oligosaccharide-linked lipid
that is recognized by a type of human receptor called CD1d-a
recognition event that is a crucial part of the immune system.
Recognizing Bacteria

CD1d belongs to a family of receptor proteins (designated CD1a-d) that
are present on the surface of two types of immune system cells known as
Langerhans and dendritic cells. These are professional antigen
presenting cells that play an important role in innate immunity. CD1
receptor recognition is vital for defense against common bacteria
because Langerhans and dendritic cells use these molecules to "present"
an immune cell known as a natural killer (NK) T cell with specific
glyco-lipid antigens (fatty molecules that are components of the
bacteria).

This presentation activates the NK T cells, and the NK T cells help to
activate other components of the immune system and defeat the
infection.

Once the NK T cells become activated, they expand in number and unleash
a torrent of action aimed at clearing the infectious agent. They begin
to secrete a large amount of two proteins-interferon-gamma, which
activates macrophages, and interleukin-4, which activates helper T
cells. The macrophages and the helper T cells then carry on the immune
response and ultimately deal with the pathogens.

NK T cells are unusual in that they fall somewhere between innate and
adaptive immunity. These cells arise in the thymus, and as mature
cells, they stimulate an adaptive immune response and regulate a range
of disease states, including diabetes, cancer, and pathogenic
infections. Evidence for the cell's role in cancer can be seen in
studies of mutant mice that are lacking NK T cells. These mice have a
higher incidence of cancer, but if the deficient mice are transplanted
with NK T cells, their prognosis much improves.

Like other T cells, NK T cells express T cell receptors
(TCR)-although without the normal antigenic variability. However, NK
T cells vary from other T cells lines in that they also express the
"NK" receptors, which are designed to detect some of the lipids that
many bacteria display on their outer surface by recognizing the CD1
receptor on the surface of the aforementioned Langerhans and dendritic
cells.

Because they are one of the fundamental molecules through which the
immune system recognizes the pathogenic world, CD1 receptors are a hot
topic of interest in biology right now. Several groups at Scripps
Research focus on CD1(see related stories on
http://www.scripps.edu/newsandviews/i_20050321/wilson.html and
http://www.scripps.edu/newsandviews/i_20041115/teyton.html.)
The First Natural CD1d Antigen

About 10 years ago, a group of scientists at Harvard Medical School
identified the first antigen bound by CD1, but it was a glycolipid from
a marine sponge and so probably not the sort of antigen that the human
immune system normally encounters.

Since then, several other antigens that bind to forms of CD1 have been
identified, including both natural human lipids and those from the cell
walls of common bacteria, such as Mycobacterium tuberculosis and
Nisseria gonorrheae.

Even so, scientists have not been able to identify any of the natural
antigens bound by CD1d-despite the fact that people have been looking
for several years.

The latest results by Wong and his colleagues appeared in two recent
articles describing, for the first time ever, bacterial antigen for the
CD1d molecule.

In the February, 2005 issue of the Proceedings of the National Academy
of Sciences, described how Wong and graduate student Douglass Wu
synthesized a bacterial glycolipid and showed that it could activate
mouse and human NK T cells in vitro. The bacterial glycolipid, which
technically is called an "alpha-galacturonosyl-ceramide," comes from a
type of rod-shaped bacteria known as Sphingomonas wittichii, which are
highly abundant in the environment.

Then, in an article that appeared in the journal Nature in March,
Wong's collaborator Mitchell Kronenberg of the La Jolla Institute for
Allergy and Immunology showed that mouse and human NK T cells also
recognized and responded to the bacterial glycolipid in vivo. They
found that the Sphingomonas glycolipid, when presented to mice as an
antigen, generated NK T cells that killed the bacteria.

"It's important to identify the real ligands that trigger NK T cell
activation, and now we are getting some," says Wong. "The next step is
to see how the glycolipid is presented to the NK T cell. [That] could
lead to the design of an antigen."

Such an antigen, says Wong, would be an interesting starting point for
the future design of vaccines. Since activated NK T cells stimulate the
production of interferon gamma, a pro-inflammatory protein that
stimulates macrophages, helper T cells, and other immune system cells,
molecules like the Sphingomonas glycolipids that activate NK T cells
can be used as adjuvants in vaccines-additives that stimulate a
non-specific immune response and boost the effectiveness of a vaccine
against a specific pathogen like HIV or Plasmodium falciparum, the
malaria pathogen.

And since NK T cells are implicated in a wide variety of non-pathogenic
diseases such as autoimmune diseases and cancer, such antigens could
also provide a key component of a new therapy for these conditions as
well.

To read the article, "Recognition of bacterial glycosphingolipids by
natural killer T cells" by Yuki Kinjo, Douglass Wu, Gisen Kim, Guo-Wen
Xing, Michael A. Poles, David D. Ho, Moriya Tsuji, Kazuyoshi Kawahara,
Chi-Huey Wong, and Mitchell Kronenberg, see the March 24, 2005 issue of
the journal Nature (434, 520-525) or go to:
http://dx.doi.org/10.1038/nature03407.

To read the article, "Bacterial glycolipids and analogs as antigens for
CD1d-restricted NKT cells" by Douglass Wu, Guo-Wen Xing, Michael A.
Poles, Amir Horowitz, Yuki Kinjo, Barbara Sullivan, Vera
Bodmer-Narkevitch, Oliver Plettenburg, Mitchell Kronenberg, Moriya
Tsuji, David D. Ho, and Chi-Huey Wong, see the February 1, 2005 issue
of the journal Proceedings of the National Academy of Sciences (102,
1351-1356) or go to: http://dx.doi.org/10.1073/pnas.0408696102.

***********

Lets see what we can find that's visual.
http://www.mc.vanderbilt.edu/microbio/vankaer/tcell.html
http://www.mc.vanderbilt.edu/microbio/vankaer/research.html
http://www.mc.vanderbilt.edu/microbio/vankaer/mhc.html
&
http://www.rcai.riken.go.jp/eng/group/regulation/

http://www.bioscience.org/2002/v7/d/racke/figures.htm

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=912

http://www.ncbi.nih.gov/IEB/Research/Acembly/av.cgi?db=human&l=CD1D

http://www.dsi.univ-paris5.fr/genatlas/fiche.php?symbol=CD1D

What can we do?

If eating wheat carbs makes your P sore.

Try rice carbs!

Or inject some n-3's every week for six weeks.

Cheaper then biologicals. I wonder how much you'd have to do?

(note: please don't try it without medical dudes to check you out.)

^^^^^^^^^^^^^^

Well. That was interesting. Explains folded proteins maybe. One little
methyl cap and who knows?

If that's all it takes to cure us. It would be cool.

Now on to the days abstracts. Loads of TNF. Isn't that where paradise
for us lives?

Two shots a week and clear in six!

TNF blockade: an inflammatory issue.

Aggarwal BB, Shishodia S, Takada Y, Jackson-Bernitsas D, Ahn KS, Sethi
G, Ichikawa H.

Cytokine Research Laboratory, Department of Experimental Therapeutics,
University of Texas, M.D. Anderson Cancer Hospital 77030, USA.
agga...@mdanderson.org

Tumor necrosis factor (TNF), initially discovered as a result of its
antitumor activity, has now been shown to mediate tumor initiation,
promotion, and metastasis. In addition, dysregulation of TNF has been
implicated in a wide variety of inflammatory diseases including
rheumatoid arthritis, Crohn's disease, multiple sclerosis, psoriasis,
scleroderma, atopic dermatitis, systemic lupus erythematosus, type II
diabetes, atherosclerosis, myocardial infarction, osteoporosis, and
autoimmune deficiency disease. TNF, however, is a critical component of
effective immune surveillance and is required for proper proliferation
and function of NK cells, T cells, B cells, macrophages, and dendritic
cells. TNF activity can be blocked, either by using antibodies
(Remicade and Humira) or soluble TNF receptor (Enbrel), for the
symptoms of arthritis and Crohn's disease to be alleviated, but at the
same time, such treatment increases the risk of infections, certain
type of cancers, and cardiotoxicity. Thus blockers of TNF that are safe
and yet efficacious are urgently needed. Some evidence suggests that
while the transmembrane form of TNF has beneficial effects, soluble TNF
mediates toxicity. In most cells, TNF mediates its effects through
activation of caspases, NF-kappaB, AP-1, c-jun N-terminal kinase, p38
MAPK, and p44/p42 MAPK. Agents that can differentially regulate TNF
expression or TNF signaling can be pharmacologically safe and effective
therapeutics. Our laboratory has identified numerous such agents from
natural sources. These are discussed further in detail.

PMID: 16331857

Cytokine targeting in psoriasis and psoriatic arthritis: beyond
TNFalpha.

MclInnes IB.

Division of Immunology, Infection and Inflammation, University of
Glasgow, Centre for Rheumatic Diseases, Glasgow, Scotland.
i.b.m...@climed.gla.ac.uk

Targeting TNFalpha provided proof of concept for the role of
pro-inflammatory cytokines in promoting cutaneous inflammation,
particularly psoriasis. Recent studies have elucidated the presence of
numerous cytokine and chemokine activities in psoriatic skin and
synovium. There is considerable interest in the potential of such
activities as novel therapeutic targets. IL-15 is an innate response
cytokine that activates leukocyte subsets via binding to its unique
IL-15Ralpha and shared beta and gamma chain receptors. IL-15 promotes T
cell memory and sustains local T cell activation, in part via
prevention of apoptosis and mediates activation of monocytes,
neutrophils and NK cells. IL-15 is up-regulated in psoriatic skin and
psoriatic arthritis synovium. IL-15 blockade in a murine model of
psoriasis led to marked suppression of typical psoriatic skin features.
Clinical intervention in other chronic inflammatory disease states is
now ongoing with encouraging early efficacy, raising the possibility
for the first time of targeting this novel inflammatory moiety in
psoriasis.

PMID: 16329645

B & S Skurkovich like Ifn's over the tnf's.

Inhibition of IFN-gamma as a method of treatment of various autoimmune
diseases, including skin diseases.

Skurkovich B, Skurkovich S.

Pediatric Infection Disease, Rhode Island Hospital, Providence, RI
2903, USA. Bskur...@pol.net

We pioneered anticytokine therapy (ACT) for autoimmune diseases (ADs).
In 1974, we proposed that hyperproduced interferon (IFN) can bring AD
and anti-IFN can be therapeutic. In 1989, we proposed removing tumor
necrosis factor (TNF)-alpha together with certain types of IFN to treat
various ADs. We found IFN in patients with different ADs and conducted
the first clinical trial of ACT in 1975. Anti-IFN-gamma and
anti-TNF-alpha work in similar ways, but the latter brings serious
complications in some patients. We obtained good, sometimes striking,
therapeutic effects treating many different Th-1-mediated ADs with
anti-IFN-gamma, including rheumatoid arthritis, multiple sclerosis
(MS), corneal transplant rejection, and various autoimmune skin
diseases such as psoriasis, alopecia areata, vitiligo, acne vulgaris,
and others. Anti-IFN-gamma was in some ways superior to anti-TNF-alpha,
which was ineffective in MS. Anti-IFN-gamma therapy holds great promise
for treating many Th-1 ADs, especially skin diseases.

PMID: 16329644

T Reg's are low for P. So raise them.

Regulatory T cells in psoriasis.

Kagen MH, McCormick TS, Cooper KD.

Psoriasis is a chronic autoimmune disease in which T lymphocytes are
thought to be central in the pathogenesis. Recently, a T cell subset
population was identified, whose role is to suppress inflammatory
responses triggered by T effector cells. T cells in this new population
are referred to as T regulatory cells. We studied their number and
activity in psoriatic lesions and found that they are both numerically
and functionally deficient in their ability to suppress the abnormally
persistent psoriatic immune response. This deficiency may shed more
light on the complex pathophysiology of psoriasis.

PMID: 16329653

To see these abstracts. Go to pubmed.com and enter the pmid #. You can
check the
related articles links on each then also.

randall...

randall

unread,

Dec 14, 2005, 2:55:27 PM12/14/05

Hi,

P news from around the world:

http://www.eurekalert.org/pub_releases/2005-12/ra-gtp121305.php
New down under T-cell peptide drug for P from Gropep.

This next alert looks very promising. It shows that the current
hypothesis
of the function of DCs in the skin may be backwards!!!

http://www.eurekalert.org/pub_releases/2005-12/yu-lcr121205.php
Langerhans cells regulate immune reactions in the skin
Researchers at Yale School of Medicine have demonstrated that
Langerhans cells in the skin, which had been thought to alert the
immune system to pathogens, instead dampen the skin's reaction to
infection and inflammation.

This has the potential to significantly alter understanding of the
mechanisms underlying many skin disorders such as psoriasis, lupus and
skin cancer.

Dendritic cells are found throughout the body and are extremely
efficient at alerting the immune system to the presence of pathogens
and other foreign materials. Langerhans cells are dendritic cells in
the skin. Skin is an important barrier to infection and it has been
generally assumed that the Langerhans cells only serve to warn the
immune system of skin pathogens.

According to the study, featured on the cover of the December 15 issue
of Immunity, Langerhans cells are not required and, in fact, inhibit or
modulate immune responses in the skin.

Daniel H. Kaplan, M.D., and Mark J. Shlomchik, M.D., used a technology
called Bacterial Artificial Chromosome transgenics to develop a mouse
model that lacks Langerhans cells in the skin from birth. They
stimulated the skin of these mice to create hypersensitivity similar to
a poison ivy reaction. They expected that mice without Langerhans cells
would have less immune response in the skin.

"Unexpectedly, instead of a decreased immune response to contact
hypersensitivity, we found a reproducible and significant increase,"
said first author Kaplan, assistant professor in the Department of
Dermatology at Yale School of Medicine. "Langerhans cells are thus not
required to generate immune responses in the skin and more profoundly,
they actually regulate immune responses in the skin."

According to senior author Shlomchik, professor of laboratory medicine
and immunobiology at Yale, "We now have a new view of these cells, not
just as sentinels or stimulators of immune reactions as previously
thought, but more as peacekeepers with the environment, which poses a
constant challenge to skin. Most such challenges are not dangerous and
do not warrant an immune response."

Langerhans cells may function generally to prevent excessive responses
in the skin. "Failure of this mechanism could result in chronic
inflammatory skin conditions like lupus and psoriasis, said Shlomchik.
"This is the new theory we would now like to test."

The findings could also have future implications for skin
transplantation, autoimmune diseases and the immune system's ability to
prevent skin cancer.
###

Other authors on the study included Mathew C. Jenison, Sem Saeland and
Warren D. Shlomchik.

The study was funded by the National Institutes of Health through the
National Institute of Arthritis and Musculoskeletal and Skin Diseases,
and the Dermatology Foundation.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Abstract time,

The Psychosocial Burden of Psoriasis.

Kimball AB, Jacobson C, Weiss S, Vreeland MG, Wu Y.

Harvard Medical School, Boston, Massachusetts, USA.

BACKGROUND: Skin diseases such as psoriasis can profoundly influence a
patient's self-image, self-esteem, and sense of well-being. Psoriasis
is a multifactorial inflammatory condition with a disease burden that
extends beyond the physical symptoms experienced by patients. Psoriasis
affects all aspects of quality of life, including physical,
psychologic, social, sexual, and occupational elements. OBJECTIVE: The
goal of this article was to review the published literature on the
impact of psoriasis on quality of life. METHODS: Relevant studies were
identified through a comprehensive search of MEDLINE, EMBASE, and the
Derwent Drug File databases of English-language articles published
between 1993 and 2005 using the terms psoriasis in combination with
quality of life, cost, cost-benefit analysis, economic, employment,
days lost, healthcare, hospitalization, managed care, outcomes
research, occupation, payers, and psychosocial. The reference lists of
identified articles were checked for additional studies that might have
been missed in the original searches. RESULTS: Data suggest that social
stigmatization, high stress levels, physical limitations, depression,
employment problems and other psychosocial co-morbidities experienced
by patients with psoriasis are not always proportional to, or predicted
by, other measurements of disease severity such as body surface area
involvement or plaque severity. CONCLUSION: It is essential to include
measures of psychosocial morbidity when assessing psoriasis severity
and treatment efficacy because of the substantial role that
psychosocial burden plays in patient perception of disease severity,
quality of life, and disease course.

PMID: 16343026

^^^^^^^^^^

This looks promising.

Evidence for susceptibility determinant(s) to psoriasis vulgaris in or
near PTPN22 in German patients.

Huffmeier U, Steffens M, Burkhardt H, Lascorz J, Schurmeier-Horst F,
Stander M, Kelsch R, Baumann C, Kuster W, Mossner R, Reich K, Wienker
TF, Traupe H, Reis A.

Institute of Human Genetics, University of Erlangen, Germany.

INTRODUCTION: Variant R620W of protein tyrosine phosphatase
non-receptor type 22 (PTPN22) has consistently been reported as
susceptibility factor for several autoimmune diseases. We were
interested in its role in susceptibility to psoriasis, furthermore
whether other disease-causing variants within PTPN22 might exist and
whether they act independently from the major risk factor for psoriasis
at HLA-C / PSORS1. METHODS: R620W was tested in a case control study
with an exploratory set of 375 independent German patients and an
enlarged sample of 418 additional patients. Analyses were extended to
linkage disequilibrium (LD) based haplotypes. Potential interaction
between one risk haplotype encompassing PTPN22 and the PSORS1
associated risk allele was tested by regression analysis. PTPN22 coding
sequence was determined in 20 patients carrying the risk haplotype.
Regression analysis as well as analysis of the strongest associated
risk haplotypes were also performed in the extended case control study.
RESULTS: R620W was not associated in both case control studies (375/793
patients) while significant association (corrected for multiple
testing) with one haplotype (C-4) of the LD block encompassing PTPN22
as well with another haplotype (B-3) within an adjacent telomeric LD
block was detected. No evidence for interaction between risk haplotype
C-4 and the HLA-C associated risk allele was found. Sequencing excluded
other coding variants within PTPN22 as basis for association findings.
Analysis of the extended study group confirmed association for
haplotypes B-3 and C-4 and independence of risk haplotypes C-4 and
PSORS1. DISCUSSION: We exclude a major role of *620W in German
psoriasis patients but suggest that (an)other susceptibility
determinant(s) within the non-coding regions of PTPN22 or its proximity
might exist that act independently from the major PSORS1 risk factor.

PMID: 16339849

randall... and thats it for today.

randall

unread,

Dec 18, 2005, 5:44:38 PM12/18/05

Hi,

P news from the UK.

http://enjoyment.independent.co.uk/books/features/article333611.ece
Christmas books: Happiness is a glass of warm milk
Misery, illness and humiliation - that's what you want from a celebrity
memoir, says Matthew Sweet. Sharon Osbourne provides plenty, but what's
Ned Sherrin so jolly about?
Published: 18 December 2005

[...]

George Melly's Slowing Down (Viking £17.99) uses Philip Larkin's "The
Old Fools" as its starting point, and the book is a highly readable
account of its author's physical collapse. George can't cut his own
toenails, he can't help himself farting as he exits a taxi, he soils
himself in the V&A and his psoriasis is so bad that his bed once
resembled "a butcher's shop in which someone had spilt several packets
of cornflakes". He is an old toad by whom it would be very nice to be
escorted down Cemetery Road.

<sniP>

They have my interest! Paints quite a picture.

Who is this fart?

Google time (hammer time-- music in brain no less)

http://www.ronniescotts.co.uk/ronnie_scotts/ronniescotts/157/08.htm

I should have been thinking ALL That Jazz

So whats the philip larkin take?

http://www.poetryconnection.net/poets/Philip_Larkin/4813

H'mmm

Doesn't much get one into the christmas spirit.

Oh well..

randall... and we know what the ultimate Xmas gift would be! Or was!

randall

unread,

Dec 20, 2005, 1:50:47 PM12/20/05

Hi,

P news from around the world.

http://www.medpagetoday.com/Dermatology/Psoriasis/tb/2361
Psoriasis Severity and Cigarettes: The Smoking Gun

By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of
Pennsylvania School of Medicine.
December 20, 2005
MedPage Today Action Points

* Explain to interested patients that in addition to the other
documented harmful effects, cigarette smoking can significantly
exacerbate psoriasis severity, particularly among women.

Review
ROME, Dec. 20 - Psoriasis joins the list of offenses committed on the
body by cigarette smoking.

People with psoriasis and a one pack-a-day smoking habit have twice the
risk of having severe psoriasis compared with less frequent smokers or
non-smokers, according to a cross-sectional study reported in the
December issue of the Archives of Dermatology.

The effect is particularly significant among women, who have a 72%
greater risk for having severe psoriasis if they are current or recent
smokers, compared with women who never took up the habit, according to
Cristina Fortes, Ph.D., and colleagues of the Istituto Dermopatico
dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico,
in Rome and the University of Montreal.

"The results of this study suggest a negative effect of cigarette
smoking on the severity of psoriasis, in particular in women," the
authors wrote. "These findings might be of clinical importance because
they would support the dermatologist's recommendation to patients with
psoriasis to quit smoking to prevent worsening of their psoriasis."

The study was part of a larger project focused on the clinical and
epidemiologic features of psoriasis and on its effects on patients'
emotional well being and quality of life.

The investigators looked at 818 men and women hospitalized for
psoriasis. Trained dermatologists evaluated the patients clinically for
severity of psoriasis and collected demographic and socioeconomic
information, as well as information on their smoking history and
clinical variables, including body mass index (BMI). They also looked
for the presence of chronic diseases such as lipid metabolic disorders,
diabetes, renal diseases, hypertension, and asthma.

The main outcome was psoriasis severity measured by the Psoriasis Area
and Severity Index (PASI), as scored by a senior dermatologist during
the early hours of hospital admission, prior to the start of therapy.
On the PASI scale, a score of 1-10 is considered to be mild psoriasis,
10-20 is moderate, and >20 is severe psoriasis.

The mean age of the 505 men and 313 women in the study was 46.8 ± 16.0
years, and the mean PASI score was 8.6 ± 5.9.

When the researchers took lifestyle and demographic factors into
account, they found that two or more glasses of alcohol per day doubled
the risk of severe psoriasis, and that family history of psoriasis was
also associated with greater risk of disease severity.

In addition, patients with PASI scores >9.7 smoked about 10 more
cigarettes per day than patients with less severe disease (24.1±14.6
vs.15.1±9.4).

Using regression analysis models, the authors found that among current
smokers the intensity of smoking was associated with psoriasis severity
(Wald test for trend: P=.007).

"Specifically, patients who smoked more than a pack of cigarettes (>20
cigarettes) daily had twice the risk of more severe psoriasis compared
with those who smoked 10 cigarettes or less per day," they wrote. "In
all smokers (including current and former smokers), cigarette-years was
associated with a 30% increased risk of more severe psoriasis for a
600-U increase (which corresponds, e.g., to 20 cigarettes per day for
30 years)."

There was also a significant gender difference. Women who were current
smokers or had only recent stopped had a 72% higher risk of severe
psoriasis than those who had never started. In addition, for women, but
not for men, the effect of cigarette-years (the product of the number
of cigarettes smoked daily and the duration in years), was significant
for disease severity (odds ratio of 1.8; 95% CI, 1.2- 2.6).
Primary source: Archives of Dermatology
Source reference:
Fortes C et al. Relationship Between Smoking and the Clinical Severity
of Psoriasis. Arch Dermatol. 2005;141:1580-1584

**********

randall

unread,

Dec 20, 2005, 6:06:16 PM12/20/05

Hi,

New abstract today that looks interesting. As to figuring out pathways.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16362825
Peptidoglycan recognition proteins Pglyrp3 and Pglyrp4 are encoded from
the epidermal differentiation complex and are candidate genes for the
Psors4 locus on chromosome 1q21.

Sun C, Mathur P, Dupuis J, Tizard R, Ticho B, Crowell T, Gardner H,
Bowcock AM, Carulli J.

Department of Genetics, BiogenIdec, Inc, 12 Cambridge Center,
Cambridge, MA, 02142, USA, john.c...@biogenidec.com.

Psoriasis is a common inflammatory skin disease caused by genetic and
environmental factors, including bacterial and viral infections. Since
the skin is in constant contact with commensal and pathogenic
microorganisms, we examined well-supported psoriasis genetic linkage
intervals to identify genes encoding innate immune pattern recognition
proteins that may play a role in pathogenesis. Two peptidoglycan
recognition proteins, Pglyrp3 and Pglyrp4, are localized to the Psors4
locus on chromosome 1q21 in a gene cluster known as the epidermal
differentiation complex (EDC). We show that these genes are expressed
in the skin as well as in germinal centers in the tonsil. We tested 13
SNPs in or near these genes for association with psoriasis in two
independent patient collections: a family-based patient set comprised
of 375 individuals from 101 families, and a case-control patient
collection of 282 patients with moderate to severe psoriasis and 192
healthy controls. In the family-based analysis, several SNPs in the
Pglyrp3-Pglyrp4 locus show association with psoriasis (0.01<P<0.05).
Multiple-SNP haplotypes incorporating Pglyrp3 and Pglyrp4 SNPs also
show significant association in the transmission disequilibrium test
(TDT; P<0.01). In the case-control test, none of the SNPs that we
tested show association with psoriasis when analyzed in single-SNP or
haplotype-based tests. The discordance between the TDT and case-control
results suggests that the two populations are significantly different
in disease etiology, that the polymorphism responsible for the Psors4
linkage is elsewhere in the Pglyrp locus, or that the causative Psors4
polymorphism is in a location near but not in the Pglyrp locus. These
data are consistent with previous reports of association of psoriasis
with genes on 1q21, and suggest a role for Pglyrps in skin biology.

PMID: 16362825

Looks interesting. We looked at peptidoglycan recently iirc.

Yep,
http://groups.google.com/groups?hl=en&q=Peptidoglycan+psoriasis+randall&qt_s=Search

So a primer is in order.

http://www.daviddarling.info/encyclopedia/P/peptidoglycan.html
A cross-linked complex of polysaccharides and peptides found in the
cell walls of bacteria. Gram-positive bacteria (so-called because they
color violet when treated appropriately with Gram stain) have a thick
layer of a peptidoglycan (or murein), the form of which determines the
organism's shape - bacilli (rod shaped), cocci (spherical shaped), or
spirilla (helical shaped). In contrast, gram-negative organisms have
only a very thin layer of peptidoglycan immediately outside their cell
membrane (about one twentieth of the thickness of that found in
gram-positive organisms). Surrounding this thin wall of peptidoglycan,
however, gram-negative organisms have a bilayered membrane composed of
phospholipid and bacterial lipopolysaccharide which has the ability to
protect the internal structures of the microbe from damaging chemicals.

^^^^^^^^

And
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16354652
Peptidoglycan recognition proteins are a new class of human
bactericidal proteins.

Lu X, Wang M, Qi J, Wang H, Li X, Gupta D, Dziarski R.

Indiana University School of Medicine-Northwest, Gary, IN 46408.

Skin and mucous membranes come in contact with external environment and
protect tissues from infections by producing antimicrobial peptides. We
report that human Peptidoglycan Recognition Proteins 3 and 4 (PGLYRP3
and PGLYRP4) are secreted as 89-115 kDa disulfide-linked homo- and
heterodimers and are bactericidal against several pathogenic and
nonpathogenic transient, but not normal flora, Gram-positive bacteria.
PGLYRP3 and PGLYRP4 are also bacteriostatic towards all other tested
bacteria, which include Gram-negative bacteria and normal flora
Gram-positive bacteria. PGLYRP3 and PGLYRP4 are also active in vivo and
protect mice against experimental lung infection. In contrast to
antimicrobial peptides, PGLYRPs kill bacteria by interacting with their
cell wall peptidoglycan, rather than permeabilizing their membranes.
PGLYRP3 and PGLYRP4 are expressed in the skin, eyes, salivary glands,
throat, tongue, esophagus, stomach, and intestine. Thus, we have
identified the function of mammalian PGLYRP3 and PGLYRP4, and show that
they are a new class of bactericidal and bacteriostatic proteins that
have different structure, mechanism of action, and expression pattern
than antimicrobial peptides.

PMID: 16354652

********************************

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608197
&
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608198

randall... gram positive bacteria with these proteins i wasn't
expecting!

randall

unread,

Dec 26, 2005, 3:26:01 PM12/26/05

Hi,

P News from around the world.

This first story shows the need to beware of NOT so Sunny side
effects of worshinPPing the SUN.

Ultraviolet B Light Exposure Associated With Increased Risk Of Skin
Cancer
http://www.medicalnewstoday.com/medicalnews.php?newsid=35241

Is it possible that holding your breathe could fix the gut some?
This is very curious.
Carbon Monoxide Helps Shut Down The Intestinal Inflammation That Causes

Ulcerative Colitis
http://www.medicalnewstoday.com/medicalnews.php?newsid=35173
<sniP>

recent scientific studies have shown that CO -- at least at low
concentrations -- has a redeeming quality: it acts as an
anti-inflammatory agent.

It is this quality, according to Plevy and colleagues, that allowed CO
to ease the symptoms of IBD in mice. The group traced the action of
inhaled CO to a protein that is produced by immune cells called
interleukin (IL)-12. IL-12 is normally produced during infection and
helps activate the immune cells that fight off the invading pathogens.
But chronic production of IL-12 in the gut also drives the inflammation
that causes ulcerative colitis. Inhaled CO inhibited the production of
IL-12, short-circuiting the disease-causing inflammation.

The researchers are now trying to unravel the specific cellular
components that are required for CO to inhibit IL-12. In the meantime,
Plevy thinks that inhaled CO might provide some relief for patients
with ulcerative colitis. But non-smokers with IBD shouldn't necessarily
break out the Marlboros, as cigarette smoking is a risk factor not only
for heart disease and cancer but also for Crohn's disease, another form
of IBD.

Two recent P abstracts from Pubmed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16374479
Investigation of the Chromosome 17q25 PSORS2 Locus in Atopic
Dermatitis.

Morar N, Bowcock AM, Harper JI, Cookson WO, Moffatt MF.

1Wellcome Trust Centre for Human Genetics, University of Oxford,
Oxford, UK.

Psoriasis and atopic dermatitis (AD) are strongly genetic and inherited
as multi-factorial traits. In both diseases, linkage has been reported
to chromosome 17q25. For psoriasis, the locus has been labelled PSORS2.
Two peaks of association here contain the psoriasis candidate genes
SLC9A3R (solute carrier family 9, isoform 3 regulatory factor), NAT9
(N-acetyltransferase superfamily), and RAPTOR (rapamycin (TOR)). We
genotyped 14 of the most significantly associated single-nucleotide
polymorphisms (SNPs) in these genes in a panel of 148 families (ECZ1)
identified through a proband with active AD. The panel contains 350
siblings and 245 sib-pairs. Replication of positive findings was sought
in a second panel, MRC-E, comprising of 278 families, 634 siblings, and
470 sib-pairs. SNP genotyping was carried out by Sequenom MassArray
technology. Using family-based tests of association (transmission
disequilibrium test), rs878906, in intron 3 of NAT9, was significantly
associated with AD (P=0.010) in the ECZ1 panel. In the MRC-E panel,
rs895691, between the end of exon 6 of SLC9A3R1 and exon 7 of NAT9, was
associated with AD (P=0.037). These were not significant when multiple
comparisons were taken into account. Haplotype analysis revealed no
significant associations in either population. These results suggest
that the psoriasis candidate genes do not account for previously
observed linkage of the 17q25 PSORS2 locus to AD.Journal of
Investigative Dermatology advance online publication, 5 January 2006;
doi:10.1038/sj.jid.5700108.

PMID: 16374479

Look at those names above. Ann Bowcock is working with these
researchers. Their
getting to-gether to nail the P pathways. This uPcoming year could see
the genetics
of the P thing rectified... (we hoPe)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16374458

Increased Neutrophil Adherence in Psoriasis: Role of the Human
Endothelial Cell Receptor Thy-1 (CD90).

Wetzel A, Wetzig T, Haustein UF, Sticherling M, Anderegg U, Simon JC,
Saalbach A.

1Department of Dermatology, Venerology and Allergy, University of
Leipzig, Leipzig, Germany.

The chronic inflammatory skin disease psoriasis is characterized by
prominent skin infiltration by neutrophils and microabscess formation.
The adhesion of leukocytes and subsequent transmigration through the
activated endothelium is one prerequisite for the accumulation of these
cells in skin. In recent studies, the human Thy-1 (CD90) was
characterized as an adhesion molecule on activated endothelial cells
(ECs) mediating the adhesion of neutrophils via the interaction with
the beta2-integrin Mac-1. Based on these novel findings, we compared
the roles of Thy-1 and ICAM-1 in the adhesion of neutrophils from
patients with psoriasis to activated ECs. The adhesion of peripheral
blood neutrophils of patients suffering from psoriasis to
Thy-1-transfected cells as well as to activated, Thy-1-expressing human
dermal microvascular ECs (HDMECs) is distinctly increased in comparison
to the adhesion of neutrophils from healthy controls. In contrast,
adherence of psoriatic neutrophils to ICAM-1 transfectants is, if at
all, only slightly enhanced compared to healthy controls. The
interaction of healthy as well as psoriatic polymorphonuclear cells to
Thy-1 transfectants and HDMECs was significantly inhibited by blocking
Thy-1 on ECs or its receptor Mac-1 on neutrophils, indicating the
importance of this interaction for the adhesion of neutrophils to
activated endothelium. In conclusion, our data indicate that the
adhesion of neutrophils to activated ECs mediated by Thy-1/Mac-1
interaction is an important attachment mechanism facilitating their
subsequent migration into lesional psoriatic skin.Journal of
Investigative Dermatology advance online publication, 22 December 2005;
doi:10.1038/sj.jid.5700072.

PMID: 16374458

This next one is NO fish story. How did human skin color get selected
and change
over millions of years?

Zebrafish reveals a one amino acid difference in humans as to skin
color,
http://www.medicalnewstoday.com/medicalnews.php?newsid=35078

If there is a P cure. Work like this will be significant.

Cedars-Sinai Researchers Demonstrate A New Way To Switch Therapeutic
Genes 'on'
And 'off'
http://www.medicalnewstoday.com/medicalnews.php?newsid=35316

Cells May Be Programmed By Their Genes, But Expression Of Those Genes
Is
Surprisingly Noisy
http://www.medicalnewstoday.com/medicalnews.php?newsid=35289

RNA, Once DNA's Less-Famous Chemical Cousin, Has Moved To Center Stage
http://www.medicalnewstoday.com/medicalnews.php?newsid=35069

And now for the Politics of funding the all to imPortant P research.

http://www.medicalnewstoday.com/medicalnews.php?newsid=35125
"Psoriasis Cure Now," a nonprofit patient group that works on
behalf of the psoriasis community, today announced its 2005 "Health
Care Advocates of the Year." The recipients are Sen. Arlen Specter of
Pennsylvania, Rep. Rosa DeLauro of Connecticut, and Rep. Ralph Regula
of Ohio.

These three lawmakers were instrumental in putting Congress on record
in support of increased federal research for psoriasis and psoriatic
arthritis. Psoriasis research funding has traditionally lagged behind
other research areas, receiving just $6.5 million last year out of a
federal medical research budget at the National Institutes of Health
(NIH) approaching $30 billion.

"People with psoriasis have no Hollywood stars or other glitzy
backers to call on for support or to bring attention to this incurable
disease," said Michael Paranzino, president of Psoriasis Cure Now.
"In fact, we have traditionally suffered in silence. Yet these
leaders took up our cause without fanfare and recognized how research
on psoriasis will help not just the millions of Americans with the
disease, but may also help us better understand other challenging
diseases. We are grateful for their service to their constituents."

"The National Institutes of Health plays an important role in medical
discoveries that improve people's health and save lives," said
Congressman Regula (Ohio-16). "I am pleased that, together with the
support of my colleagues, we have been able to direct some of NIH's
focus towards this disease which affects millions of Americans."

Psoriasis is an incurable, recurring disease of the immune system that
can first strike at any age, causing dry, painful skin lesions that can
crack, bleed and itch. Many people with psoriasis also have psoriatic
arthritis, a chronic, progressive and debilitating inflammatory disease
that often causes joint pain, stiffness and swelling, as well as bone
damage. Studies this year found a higher incidence of autism in
children of mothers with psoriasis, and a higher incidence of
cardiovascular death among patients with severe psoriasis. People with
psoriasis also have higher rates of depression and suicidal ideation.

"Congress really came together this year on behalf of psoriasis
patients and their families," Paranzino added, "and Senator
Specter, Congressman Regula and Congresswoman DeLauro led the way. A
cure will come more quickly thanks to their efforts."

According to the NIH, there are as many as 7.5 million Americans with
psoriasis, including an estimated 75,000 people with psoriasis in
Connecticut; about 270,000 with psoriasis in Ohio; and about 285,000
with psoriasis in Pennsylvania. Each of these states also has important
psoriasis research centers, including the University of Pennsylvania,
Case Western Reserve University and Yale University.

"Cutting edge research like that being conducted at centers such as
Yale University will help us find better treatments and ultimately a
cure for psoriasis," said Congresswoman DeLauro (Conn.-3). "Federal
funding for this research is critical, which is why I have fought in
Congress to ensure psoriasis research continues. I am honored to be
recognized by Psoriasis Cure Now for this work."

Psoriasis Cure Now is currently urging psoriasis patients and their
loved ones to send Congress thank you notes from their home page at
www.psorcurenow.org .

***************

More abstracts dealing with DCs and gut things.

The neuropeptide vasoactive intestinal Peptide generates tolerogenic
dendritic cells.

Delgado M, Gonzalez-Rey E, Ganea D.

Department of Biological Sciences, Rutgers University, Newark, NJ
07102.

Tolerogenic dendritic cells (DCs) play an important role in maintaining
peripheral tolerance through the induction/activation of regulatory T
cells (Treg). Endogenous factors contribute to the functional
development of tolerogenic DCs. In this report, we present evidence
that two known immunosuppressive neuropeptides, the vasoactive
intestinal peptide (VIP) and the pituitary adenylate cyclase-activating
polypeptide (PACAP), contribute to the development of bone
marrow-derived tolerogenic DCs in vitro and in vivo. The
VIP/PACAP-generated DCs are CD11c(low)CD45RB(high), do not up-regulate
CD80, CD86, and CD40 following LPS stimulation, and secrete high
amounts of IL-10. The induction of tolerogenic DCs is mediated through
the VPAC1 receptor and protein kinase A, and correlates with the
inhibition of IkappaB phosphorylation and of NF-kappaBp65 nuclear
translocation. The VIP/PACAP-generated DCs induce functional Treg in
vitro and in vivo. The VIP/DC-induced Treg resemble the previously
described Tr1 in terms of phenotype and cytokine profile, suppress
primarily Th1 responses including delayed-type hypersensitivity, and
transfer suppression to naive hosts. The effect of VIP/PACAP on the
DC-Treg axis represents an additional mechanism for their general
anti-inflammatory role, particularly in anatomical sites which exhibit
immune deviation or privilege.

PMID: 16301637

Dendritic cell-associated C-type lectin 2 (DCAL-2) alters dendritic
cell maturation and cytokine production.

Chen CH, Floyd H, Olson NE, Magaletti D, Li C, Draves K, Clark EA.

Department of Immunology, University of Washington, Seattle, WA, USA;
Regional Primate Research Center, University of Washington, Seattle,
WA, USA.

Dendritic cell (DC)-associated C-type lectins (CLR) take up antigens to
present to T cells and regulate DC functions. DCAL-2 is a CLR with a
cytosolic immunoreceptor tyrosine inhibitory motif (ITIM), which is
restricted to immature DCs (iDCs), monocytes and CD1a(+) DCs.
Cross-linking DCAL-2 on iDCs induced protein tyrosine phosphorylation
and MAPK activation as well as receptor internalization. To test if
DCAL-2 is involved in DC maturation and cytokine expression, we
stimulated iDCs with anti-DCAL-2 mAb with or without LPS, zymosan or
CD40L. While anti-DCAL-2 did not induce iDCs to mature, it did
up-regulate CCR7 expression and IL-6 and IL-10 production. DCAL-2
signals augmented DC maturation induced by LPS or zymosan, increasing
both CCR7 and DC-LAMP expression. Interestingly, DCAL-2 ligation had
the opposite effects on TLR vs. CD40L signaling: anti-DCAL-2 suppressed
TLR-induced IL-12 expression, but significantly enhanced CD40L-induced
IL-12 production. DCAL-2 ligation also suppressed the ability of
TLR-matured-DCs to induce IFN-gamma-secreting Th1 cells but augmented
the capacity of CD40L-matured-DCs to polarize naive T cells into Th1
cells. Thus, DCAL-2 may program DCs differently depending on whether
DCs are signaled via TLRs or by T cells. DCAL-2 may be a potential
immunotherapeutic target for modulating autoimmune diseases or for
developing vaccines.

PMID: 16239426

Selective activation of peripheral blood T cell subsets by endotoxin
infusion in healthy human subjects corresponds to differential
chemokine activation.

De AK, Miller-Graziano CL, Calvano SE, Laudanski K, Lowry SF, Moldawer
LL, Remick DG Jr, Rajicic N, Schoenfeld D, Tompkins RG.

Department of Surgery, University of Rochester Medical Center,
Rochester, NY 14627, USA.

Although activation of human innate immunity after endotoxin
administration is well established, in vivo endotoxin effects on human
T cell responses are not well understood. Most naive human T cells do
not express receptors for LPS, but can respond to endotoxin-induced
mediators such as chemokines. In this study, we characterized the in
vivo response of peripheral human T cell subsets to endotoxin infusion
by assessing alterations in isolated T cells expressing different
phenotypes, intracellular cytokines, and systemic chemokines
concentration, which may influence these indirect T cell responses.
Endotoxin administration to healthy subjects produced T cell activation
as confirmed by a 20% increase in intracellular IL-2, as well as
increased CD28 and IL-2R alpha-chain (CD25) expression. Endotoxin
induced indirect activation of T cells was highly selective among the T
cell subpopulations. Increased IL-2 production (36.0 +/- 3.7 to 53.2
+/- 4.1) vs decreased IFN-gamma production (33.8 +/- 4.2 to 19.1 +/-
3.2) indicated selective Th1 activation. Th2 produced IL-13 was
minimally increased. Differentially altered chemokine receptor
expression also indicated selective T cell subset activation and
migration. CXCR3+ and CCR5+ expressing Th1 cells were decreased (CXCR3
44.6 +/- 3.2 to 33.3 +/- 4.6 and CCR5 24.8 +/- 2.3 to 12 +/- 1.4),
whereas plasma levels of their chemokine ligands IFN-gamma-inducible
protein 10 and MIP-1alpha were increased (61.4 +/- 13.9 to 1103.7 +/-
274.5 and 22.8 +/- 6.2 to 55.7 +/- 9.5, respectively). In contrast,
CCR4+ and CCR3 (Th2) proportions increased or remained unchanged
whereas their ligands, eotaxin and the thymus and activation-regulated
chemokine TARC, were unchanged. The data indicate selective activation
among Th1 subpopulations, as well as differential Th1/Th2 activation,
which is consistent with a selective induction of Th1 and Th2 chemokine
ligands.

PMID: 16237112

Regulation of dendritic cell function by pathogen-derived molecules
plays a key role in dictating the outcome of the adaptive immune
response.

Pearce EJ, Kane CM, Sun J.

Department of Pathobiology, School of Veterinary Medicine, University
of Pennsylvania, Philadelphia, Pa., USA.

There is increasing awareness that dendritic cells (DCs) can interpret
pathogen-inherent signals and play a pivotal role in polarizing Th cell
differentiation. Polarized Th1 responses are induced by DCs, which
respond to pathogen-derived TLR ligands to mature and produce IL-12 and
related cytokines that are instrumental in Th1 cell outgrowth. In
contrast, DCs exposed to SEA (soluble egg Ag from the helminth parasite
Schistosoma mansoni) retain a (modified) immature phenotype and induce
Th2 responses. In addition to providing positive signals for Th1 cell
development, DCs activated to mature by TLR-engagement also provide a
potent negative signal that prevents the development of Th2 cells.
Production of this signal is dependent upon a MyD88-dependent signaling
pathway in DCs. In contrast, exposure of DCs to SEA severely limits
their ability to respond to inflammatory TLR ligands such as LPS and
CpG. Thus as part of their pathogen-specific response programs, DC can
exert negative as well as positive signals for Th response
polarization. These effects may have powerful and systemic effects on
disease outcome.

PMID: 16210904

Conjugated linoleic acid suppresses NF-kappaB activation and IL-12
production in dendritic cells through ERK-mediated IL-10 induction.

Loscher CE, Draper E, Leavy O, Kelleher D, Mills KH, Roche HM.

Department of Clinical Medicine, Institute of Molecular Medicine,
Dublin, Ireland .

Polyunsaturated fatty acids (PUFA) have been shown to modulate immune
responses and have therapeutic effects in inflammatory disorders.
However, the influence of PUFA on dendritic cells (DC), key cells of
the innate immune system in shaping adaptive immune responses, has not
yet been defined. In this study, we examine the effects of the cis-9,
trans-11 isomer of conjugated linoleic acid (c9, t11-CLA), a dietary
PUFA found in meat and dairy products, on murine DC activation.
Treatment of DC with c9, t11-CLA suppressed LPS-induced IL-12, enhanced
IL-10R expression, and enhanced IL-10 production at the transcriptional
and protein level. The suppression of IL-12 by c9, t11-CLA was found to
be IL-10 dependent. We investigated the involvement of the MAPK, ERK,
and the transcription factor, NF-kappaB, in this IL-10-mediated effect.
c9, t11-CLA enhanced ERK activation after LPS stimulation, and
inhibition of ERK resulted in abrogation of IL-10 and recovery of IL-12
production. c9, t11-CLA decreased NF-kappaB:DNA binding after LPS
stimulation, which was concomitant with delayed translocation of
NF-kappaBp65 into the nucleus and an increase in IkappaBalpha. These
effects were reversed by addition of a neutralizing anti-IL-10 Ab. Our
findings demonstrate that c9, t11-CLA suppresses IL-12 production by
LPS-stimulated DC by ERK mediated IL-10-induction. Furthermore, these
IL-10-mediated effects are dependent on inhibition of NF-kappaB
activation. This is the first study to demonstrate that c9, t11-CLA can
enhance transcription and production of the anti-inflammatory cytokine
IL-10, while inhibiting the Th1-promoting cytokine IL-12, and may
explain certain of its immunosuppressive properties.

PMID: 16210601

Siglecs?the major subfamily of I-type lectins
Ajit Varki1,2,3,4 and Takashi Angata5

2 Department of Medicine, 3 Department of Cellular & Molecular
Medicine, and 4 Glycobiology Research and Training Center, University
of California, San Diego, La Jolla, CA 92093; and 5 Research Center for
Glycoscience, National Institute of Advanced Industrial Science and
Technology, Tsukuba, Ibaraki 305-8568, Japan

1 To whom correspondence should be addressed; e-mail:
varki...@ucsd.edu

Received on April 25, 2005; revised on July 2, 2005; accepted on July
2, 2005

Animal glycan-recognizing proteins can be broadly classified into two
groups?lectins (which typically contain an evolutionarily conserved
carbohydrate-recognition domain [CRD]) and sulfated glycosaminoglycan
(SGAG)-binding proteins (which appear to have evolved by convergent
evolution). Proteins other than antibodies and T-cell receptors that
mediate glycan recognition via immunoglobulin (Ig)-like domains are
called "I-type lectins." The major homologous subfamily of I-type
lectins with sialic acid (Sia)-binding properties and characteristic
amino-terminal structural features are called the "Siglecs"
(Sia-recognizing Ig-superfamily lectins). The Siglecs can be divided
into two groups: an evolutionarily conserved subgroup (Siglecs-1, -2,
and -4) and a CD33/Siglec-3-related subgroup (Siglecs-3 and -5?13 in
primates), which appear to be rapidly evolving. This article provides
an overview of historical and current information about the Siglecs.

Key words: Siglecs / sialic acids / lectins / immunoglobulin
superfamily / evolution

1 The term "sialome" is coined here to denote the total complement of
sialic acid types and linkages and their modes of presentation on a
particular organelle, cell, tissue, organ, or organism?as found at a
particular time and under specific conditions.

2 The "Red Queen" effect in evolution is based on the observation to
Alice by the Red Queen in Lewis Carroll?s "Through the Looking
Glass"-that "it takes all the running you can do, to keep in the same
place." Thus, complex multicellular animals with long life cycles must
rapidly evolve to survive the onslaught of microbial pathogens that can
replicate much faster.

randall... news snooze.. keep running alice!

randall

unread,

Jan 4, 2006, 3:30:10 PM1/4/06

Hi,

First post of the NEW YEAR for P news.

Will this be the YEAR?

I hoPe so! Let's Pray right now.

OH GOD, ALLAH , Buddah, please cure us this year.

Ok back to more human endeavors.

Lets try pubmed.

Here's a good one.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16389548
SHP-1 promoter 2 methylation in normal epithelial tissues and
demethylation in psoriasis.

Ruchusatsawat K, Wongpiyabovorn J, Shuangshoti S, Hirankarn N,
Mutirangura A.

Inter-Department of Biomedical Sciences, Graduate School, Faculty of
Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.

SHP-1 promoter hypermethylation has been studied in hematopoietic cells
and observed only in various types of lymphoma and leukemia. This study
reports a contrasting situation in normal epithelial tissues and an
association with skin pathogenesis, particularly in psoriasis. We
investigated several cell lines, five of them were epithelial and six
were hematopoietic, white blood cells from normal, healthy donors, and
normal microdissected epithelium of kidney, liver, breast, cervix,
lung, prostate, bladder, and skin. Interestingly, promoter 2
hypermethylation was apparent in all epithelial cell lines and tissues.
However, distinctive degrees of demethylation were noted in some skin
samples. The methylation patterns of each cell line corresponded to
their mRNA isoforms, in that isoforms I and II could not be detected
with either promoter 1 or 2 hypermethylation, respectively. We further
explored whether an enhanced degree of demethylation could be observed
in various dermatopathology lesions. While the promoter 2 methylation
levels of squamous cell cancers, eczemas, and normal skins were not
different, a significant degree of demethylation can be observed in
psoriasis (p<0.005). In addition, psoriasis displays a higher level of
SHP-1 isoform II than normal skin (p<0.05). In conclusion, this study
discovered an unprecedented role of SHP-1 methylation in
tissue-specific expression and its alteration in a nonmalignant human
disease besides the transcription inhibition in leukemia and lymphoma.
Furthermore, the promoter demethylation may play an important role in
skin pathogenesis by enhancing SHP-1 isoform II transcription in
psoriatic skin lesions.

PMID: 16389548

Lets do some P group searches of methylation.

http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=methylation&qt_g=1&searchnow=Search+this+group

And hyPerMethylation

http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=+hypermethylation&qt_g=1&searchnow=Search+this+group

**********

I take this next one. I use the Sadaf product as it's so inexpensive.

Curcumin: getting back to the roots.

Shishodia S, Sethi G, Aggarwal BB.

Cytokine Research Laboratory, Department of Experimental Therapeutics,

The University of Texas M. D. Anderson Cancer Center, Box 143, 1515
Holcombe Boulevard, Houston, TX 77030. agga...@mdanderson.org.

The use of turmeric, derived from the root of the plant Curcuma longa,
for treatment of different inflammatory diseases has been described in
Ayurveda and in traditional Chinese medicine for thousands of years.
The active component of turmeric responsible for this activity,
curcumin, was identified almost two centuries ago. Modern science has
revealed that curcumin mediates its effects by modulation of several
important molecular targets, including transcription factors (e.g.,
NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g.,
COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g.,
cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines),
receptors (e.g., EGFR and HER2), and cell surface adhesion molecules.
Because it can modulate the expression of these targets, curcumin is
now being used to treat cancer, arthritis, diabetes, Crohn's disease,
cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis,
and other pathologies. Interestingly, 6-gingerol, a natural analog of
curcumin derived from the root of ginger (Zingiber officinalis),
exhibits a biologic activity profile similar to that of curcumin. The
efficacy, pharmacologic safety, and cost effectiveness of curcuminoids
prompt us to "get back to our roots."

PMID: 16387689

Whoops. I'm sliPPing. I use ginger with my shakes and have been out for
a week or so.

Yikes. Got to hit the grocery store and freeze up some ginger.

*********************

The role of interleukin-12 in the pathogenesis of psoriasis.

Shaker OG, Moustafa W, Essmat S, Abdel-Halim M, El-Komy M.

Department of Biochemistry, Faculty of Medicine, Cairo University,
Egypt.

OBJECTIVES:: To verify the role of IL-12 in the pathogenesis of
psoriasis and determine its relation to IFNgamma. DESIGN AND METHODS::
Skin biopsies from lesional and non-lesional skin of 30 patients and 10
healthy controls were obtained for quantitative PCR examination of
IL-12 (P40) and IFNgamma mRNA as well as in situ PCR of IL-12 (P40) and
IFNgamma mRNA. RESULTS:: IL-12 and IFNgamma levels were higher in
lesional skin than in non-lesional and control skin. A significant
correlation between IL-12 and IFNgamma was found. By in situ PCR
hybridization, IL-12 expression was only found in the dermis, while
IFNgamma was invariably expressed in the dermis and/or epidermis.
CONCLUSION:: We suggest that IL-12 independently and through IFNgamma
induction may have a crucial role in the development of the active
psoriatic lesion itself, where it is probably produced locally in the
dermis as a step in the evolution of the psoriatic lesion.

PMID: 16386240

We know about IL-12 don't we?

Sure,

http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=il-12&qt_g=1&searchnow=Search+this+group

This shows the IL-12, mac's, TNF with Th1.
http://www.iir.suite.dk/IIR/06inf/inf_bac.htm

This shows the same thing and adds in CJun and stat4,
http://www.biocarta.com/pathfiles/h_IL12Pathway.asp

This one has citrulline and arginine with Jak2,
http://www.biocarta.com/pathfiles/m_no2il12Pathway.asp

*************************

And look at this,

If smoking is so bad,
http://news.google.com/news?group=alt.support.skin-diseases.psoriasis&qt_g=1&searchnow=Search_this_group&tab=in&ie=UTF-8&scoring=d&q=psoriasis+smoke&btnG=Search+News

Then what about this,

http://www.sciencedaily.com/releases/2006/01/060103084934.htm
Carbon Monoxide Soothes Inflammatory Bowel Disease

Doctors have long known that smokers rarely suffer from a common form
of inflammatory bowel disease (IBD) called ulcerative colitis, but they
didn't know why. A new study in the December 19 issue of The Journal of
Experimental Medicine might help explain this apparent resistance.
Scott Plevy and his colleagues at the University of Pittsburgh now show
that carbon monoxide (CO), a component of cigarette smoke, helps shut
down the intestinal inflammation that causes ulcerative colitis.

CO is best known as a toxic air pollutant, but small amounts of this
gas are also produced in the human body as a normal byproduct of
metabolism, suggesting that the effects of CO must not be all bad. High
dose CO gas is lethal, because it robs the body of life-sustaining
oxygen. It is this asphyxiant property of CO that has earned it a bad
reputation. But recent scientific studies have shown that CO -- at

least at low concentrations -- has a redeeming quality: it acts as an
anti-inflammatory agent.

****************

We just need to block the IL-12 pathway with some small amout of cig
smoke.

Does cannabis CO work also?

Lets check the web,
http://www.rxmarihuana.com/shared_comments/Psoriasis4.htm

Thats one guy.

Here's the Canadian take,
http://www.medicalmarihuana.ca/patients.html
(see second article on this last link. The guitar guy with P)

Still only one link on pubmed,
Pharmacological properties and therapeutic possibilities for drugs
acting upon endocannabinoid receptors.

Fowler CJ.

Department of Pharmacology and Clinical Neuroscience, Umea University,
SE-901 87 Umea, Sweden. christoph...@pharm.umu.se

Clinical trial data are beginning to emerge with respect to the
therapeutic efficacy of cannabis extracts for the treatment of chronic
pain. Although there is some evidence of efficacy, a major issue
concerns the narrow margin between doses producing therapeutic effects
and those producing the "highs" associated with cannabis misuse. In
addition, long-term use is associated with an increased risk of
psychiatric illness. These negative aspects constrain the doses of
cannabis extracts and psychoactive cannabinoids that can be given to
patients, and raise the risk that properly conducted clinical trials
with too low dosages will impact negatively on subsequent drug
development in this field. However, recent research has opened up a
number of avenues whereby compounds acting directly upon cannabinoid
(CB) receptors may have therapeutic potential. In this review, two such
areas are discussed, namely a) the possible use of peripherally acting
CB agonists and CB2 receptor-selective agonists for the treatment of
pain, and b) the possible utility of CB2 receptor agonists for the
prevention of stress-induced exacerbations of skin disorders such as
psoriasis. A second area of drug development at present is that of CB1
receptor antagonists/inverse agonists, spearheaded by rimonabant, for
the treatment of obesity and as an aid for smoking cessation. An
important aspect of these compounds is their efficacy and selectivity,
and this is discussed in detail in the present review.

PMID: 16375686

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16266285&query_hl=4&itool=pubmed_docsum
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16133420&query_hl=4&itool=pubmed_docsum
&
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16023222&query_hl=4&itool=pubmed_docsum

randall... will the cure be a cannabis link? Or methylation thing? Stay
HaPPy!

randall

unread,

Jan 8, 2006, 3:29:09 PM1/8/06

Hi,

The only news article that caught my eye this week besides the
PTH thing that JXStern and L hashed over is this,

http://www.medicalnewstoday.com/medicalnews.php?newsid=35856
Examining How One Disease May Prevent Another, UCLA

<sniP>

-- Leprosy patients have severe immune defects and cutaneous anergy --
an inability to respond to skin testing. They hardly ever get
psoriasis, a skin disorder. Starvation was used since biblical times
for the treatment of seizures, which were believed to be demons. A 1924
discovery showed that a diet rich in fat and low in carbohydrates
mimicked starvation by causing ketonemia and also controlled seizures.
The ketogenic diet is still used today for cases of epilepsy resistant
to medication.

*****

Isn't leprosy a Th2 condition? While P is a Th1.

Shall I check it?

Yep,

Well. This one says its a reduced Th1. So that means th2 by default.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15356162
T cell production of IFN-gamma contributes to host defense against
infection by intracellular pathogens, including mycobacteria.
Lepromatous leprosy, the disseminated form of infection caused by
Mycobacterium leprae, is characterized by loss of cellular response
against the pathogen and diminished Th1 cytokine production. <sniP>

____________________________________________________________________

Lets find the pumbed on the top link.

OK,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16396876

Disease versus disease: how one disease may ameliorate another.

Stiehm ER.

Department of Pediatrics, Mattel Children's Hospital, UCLA, Los
Angeles, California 90095, USA. est...@mednet.ucla.edu

Systemic disease, either genetic or acquired, may prevent or decrease
the severity of another disease. These observations have led to
important therapeutic advances. The best-known examples are Edward
Jenner's use in 1798 of cowpox to prevent smallpox and J.B. Haldane's
1942 observation that erythrocyte disorders such as thalassemia and
sickle cell disease modify the severity of malaria. Patients with and
carriers of cystic fibrosis may have genetic resistance to tuberculosis
and/or secretory diarrhea. The beneficial effects of undernutrition
have led to therapeutic diets for seizures, celiac disease, type 2
diabetes, and inflammatory bowel disease. Finasteride for prostatic
hypertrophy was developed after the observation that patients with male
pseudohermaphrodism resulting from 5-alpha-reductase mutations do not
develop prostatic hypertrophy. Rh immunoglobulin for Rh hemolytic
disease prevention followed the observation that ABO incompatibility
prevented Rh sensitization. The natural immunosuppression of measles
may cause remission of nephrosis, and that of leprosy prevents
psoriasis. Patients with one form of agammaglobulinemia (X-linked)
never get Epstein-Barr virus infection, and patients with another form
(common variable) are seemingly cured by HIV infection. HIV/AIDS is
prevented or modified by co-receptor mutations (notably the CCRDelta32
chemokine mutation), HIV-2, or GB virus C infection. Additional
exploration of these genetic, infectious, and metabolic influences on
disease severity may provide new therapeutic approaches to HIV and
other diseases.

PMID: 16396876

-------------------------------------------------------------------------------------------------

So the folks with leprosy have a haplotype problem with IL-10.

They have to much and psoriatics have to little.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16163478

People with atopy and microbial issues have a IL-10 abundance,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16185274

And here are nearly 500 abstracts on the effects of IL-10, or should i
say the lack
of il-10 and psoriasis,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=15180472&tool=ExternalSearch

I wonder if i've posted that many hits to the group yet?

Ok, i'm checking.

NoPe! only 87,
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?group=alt.support.skin-diseases.psoriasis&q=il-10+randall&qt_g=1&searchnow=Search+this+group

Lets try all groups for P and IL-10,

http://groups.google.com/groups?q=il-10+psoriasis&qt_s=Search

303. Not bad.

I bet we can find 10X's that on a web search.

http://www.google.com/search?q=il-10%20psoriasis&qt_s=Search&sa=N&tab=gw

That was a safe bet. More like 100X's plus an extra 15K kicker.

--------------------------------------------------------------------------------------------------------

Will someone come up with a safe way to induce IL-10 in the plaques
this year?

They already have a cream to induce the very factors that cause
psoriasis
for *curing* cancer. It's called imiquimod. It safely induces TNF and
IFN right
in the cancers.

http://www.google.com/search?hl=en&lr=&q=imiquimod&btnG=Search&sa=N&tab=gw

You'd think they'd have come up with a cream that simply spurs on IL-10
that
we could safely put on plaques. Even at $350 a pop for a tub would be a
bargain,
if you were moderate to mild.

Well. Gottta go.

randall... Dreaming of ways to make P easier to live with. It ain't
LeProsy!

randall

unread,

Jan 10, 2006, 2:11:55 PM1/10/06

Hi,

P news from around the world.

http://www.israel21c.org/bin/en.jsp?enDispWho=Articles%5El1198&enPage=BlankPage&enDisplay=view&enDispWhat=object&enVersion=0&enZone=Health
Israeli scientists discover molecular trigger for psoriasis
By ISRAEL21c staff January 10, 2006

An immune molecule that normally assists in cell 'suicide' may be an
important trigger in the development of the common skin disease
psoriasis, according to scientists from the Technion-Israel Institute
of Technology and State University of New York, Stony Brook.

According to the National Psoriasis Foundation in the United States,
one to three percent of the world's population suffers from psoriasis.
About 30 percent of people with psoriasis have severe cases, where the
affected skin covers more than 3 percent of their body. In some people,
the disease is associated with a form of arthritis.

The culprit, a molecule called Fas, acts as a middleman between
activated immune cells and a handful of inflammatory hormones involved
in psoriasis flare-ups, say Technion researcher Dr. Amos Gilhar and
colleagues. The study appears in the January American Journal of
Pathology.

Psoriasis is a non-contagious, lifelong skin disease that usually
appears as scaly and inflamed patches of skin, although it can take
several different forms. In patients with psoriasis, the white blood
cells that make up the body?s immune defense system go into overdrive,
triggering other immune responses that pile up skin cells at an
abnormal rate.

Current treatments for psoriasis such as the drug Enbrel focus on these
inflammatory hormones, but the researchers were able to stop the
development of psoriasis in mice long before these hormones came into
play by injecting an Fas-blocking antibody.

"The finding that antibodies to Fas can prevent psoriasis further
demonstrates the complexity of the disease and its numerous molecular
pathways," Gilhar says.

Dr. Alice Gottlieb, chair of the Clinical Research Center at the Robert
Wood Johnson Medical School in New Jersey agrees. "This research shows
that activation of the Fas pathway is important in starting the ball
rolling in psoriasis," comments Gottlieb (who was not involved with
this study). "These findings could have implications for other immune
diseases such as rheumatoid arthritis and Crohn's disease."

The researchers suspected that the Fas molecule was in the middle of
this process, since it is found at high levels in psoriatic skin and
leads an intriguing dual life. Most of the time, Fas guides the normal
process of cell suicide called apoptosis. But in cells where apoptosis
is blocked by other molecules, as it is in psoriatic cells, Fas
switches roles and encourages the production of common inflammatory
hormones instead.

To figure out exactly where Fas stood in the development of psoriasis,
Gilhar and colleagues transferred grafts of clear, non-involved skin
from human psoriasis patients to mice. They injected the mice with
white blood cells bearing the Fas molecule on their surfaces to
jump-start the formation of psoriatic skin lesions.

By blocking Fas action with a special antibody, the researchers were
able to show that Fas actually is the key middleman in psoriasis
formation. Without Fas, the natural killer cells were unable to trigger
the production of the inflammatory hormones that lead to the
characteristic skin thickening and other signs of psoriasis.

There is some evidence that Fas is involved in other skin conditions
such as eczema, so future treatments targeting the Fas pathway may
prove useful for a variety of diseases, suggests Dr. Richard Kalish,
Gilhar's collaborator from SUNY Stony Brook. However, researchers need
to develop a human antibody to Fas before the technique could be tested
in people.

"The current study is one of the many wonderful papers that have come
out of this very productive collaboration across many miles between Dr.
Gilhar and Dr. Kalish," says Gottlieb.

#####################################

Whats fas?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16400020
Fas pulls the trigger on psoriasis.

Gilhar A, Yaniv R, Assy B, Serafimovich S, Ullmann Y, Kalish RS.

Laboratory for Skin Research, Rappaport Building, Technion Faculty of
Medicine, P.O. Box 9649, Bat-Galim, Haifa, 31096, Israel.
flig...@matat.health.gov.il.

Fas/FasL signaling is best known for induction of apoptosis. However,
there is an alternate pathway of Fas signaling that induces
inflammatory cytokines, particularly tumor necrosis factor (TNF)-alpha
and interleukin (IL)-8. This pathway is prominent in cells that express
high levels of anti-apoptotic molecules such as Bcl-xL. Because
TNF-alpha is central to the pathogenesis of psoriasis and psoriatic
epidermis has a low apoptotic index with high expression of Bcl-xL, we
hypothesized that inflammatory Fas signaling mediates induction of
psoriasis by activated lymphocytes. Noninvolved skin from psoriasis
patients was grafted to beige-severe combined immunodeficiency mice,
and psoriasis was induced by injection of FasL-positive autologous
natural killer cells that were activated by IL-2. Induction of
psoriasis was inhibited by injection of a blocking anti-Fas (ZB4) or
anti-FasL (4A5) antibody on days 3 and 10 after natural killer cell
injection. Anti-Fas monoclonal antibody significantly reduced cell
proliferation (Ki-67) and epidermal thickness, with inhibition of
epidermal expression of TNF-alpha, IL-15, HLA-DR, and ICAM-1. Fas/FasL
signaling is an essential early event in the induction of psoriasis by
activated lymphocytes and is necessary for induction of key
inflammatory cytokines including TNF-alpha and IL-15.

PMID: 16400020

I suppose we can find more on this later.

&&&&&&&&&&&&&&&&&&&&&&&&&&&

More of the same,
http://www.newswise.com/articles/view/517116/

May as well have the first two sources to this story out.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

http://www.cancerpage.com/news/article.asp?id=9257

Some Autoimmune Disorders Linked to Increased Risk of Non-Hodgkin
Lymphoma

NEW YORK JAN 09, 2006 (Reuters Health) - Certain autoimmune disorders
appear to increase the risk of non-Hodgkin lymphoma (NHL), according to
a report in the January 4, 2006 Journal of the National Cancer
Institute.

"Some (namely rheumatoid arthritis, Sjögren syndrome, systemic lupus
erythematosus and celiac disease, and some other disorders not included
in the present study) but not all autoimmune and inflammatory disorders
appear to be associated with an increased lymphoma risk," Dr. Karin
Ekstrom Smedby from the Karolinska Institute, Stockholm, Sweden told
Reuters Health. "Severe and longstanding inflammation is likely to be a
key determinant behind this elevated risk."

Dr. Smedby and colleagues used the Scandinavian Lymphoma Etiology
(SCALE) study to assess several autoimmune and chronic inflammatory
disorders in relation to risks of NHL overall, risks of major NHL
subtypes, and anatomic locations of tumors.

The diagnosis of rheumatoid arthritis was associated with a 50%
increased relative risk of NHL, the authors report, especially diffuse
large B-cell and lymphoplasmacytic lymphoma. The risk was significantly
elevated only among those who had required immunosuppressant therapy.

Primary Sjögren syndrome increased the overall risk of NHL 6-fold, the
report indicates, with statistically significant increases in the risk
of diffuse large B-cell and marginal zone lymphoma.

Systemic lupus erythematosus was associated with a 4.6-fold increased
risk of NHL overall and a 6-old increased risk of diffuse large B-cell
lymphoma, the researchers note, and celiac disease was associated with
a 3-fold increased risk for diffuse large B-cell lymphoma and nearly a
20-fold increased risk for T-cell lymphoma.

"Increased NHL risks in these conditions were associated not with
treatment but with factors that relate to disease severity and
antigenic drive," the authors explain.

Inflammatory bowel disease, diabetes mellitus, sarcoidosis, and
psoriasis were not associated with an overall increased risk of NHL,
the investigators say.

"An important and somewhat novel finding in this study was that all
four disorders found to be associated with an increased lymphoma risk
were associated with one lymphoma subtype in particular, namely diffuse
large B-cell lymphoma," Dr. Smedby said. "This may imply common
pathogenetic mechanisms, for example, chronic antigen stimulation."

"It is important that doctors keep in mind the existence of the risk
increase and that we learn to identify the patients with these
disorders that are at highest risk of developing lymphoma," Dr. Smedby
concluded.

SOURCE:

* J Natl Cancer Inst 2006;98:51-60

***********************************************

http://www.docguide.com/news/content.nsf/news/8525697700573E18852570F20051D6D3

FDA Approves Taclonex (Calcipotriene/Betamethasone Dipropionate), Once
Daily Therapy for Treatment of Psoriasis

ROCKAWAY, NJ -- January 10, 2006 -- Warner Chilcott and LEO Pharma
announced today that the United States Food and Drug Administration
(FDA) has approved the New Drug Application (NDA) for Taclonex(R).

LEO Pharma submitted the NDA for Taclonex to the FDA in March 2005.
Taclonex is a topical ointment containing a combination of
calcipotriene 0.005% and betamethasone dipropionate 0.064% for the
treatment of psoriasis vulgaris in adults. Taclonex is sold outside the
U.S. as Dovobet(R) or Daivobet(R).

Warner Chilcott acquired the U.S. marketing rights for Dovonex(R)
(calcipotriene (calcipotriene 0.005%), the leading non-steroidal
topical treatment for psoriasis in the U.S., from Bristol-Myers Squibb
Company as of January 1. Warner Chilcott is now LEO Pharma's exclusive
licensee of Taclonex and Dovonex in the United States. Warner Chilcott
expects to launch Taclonex in the first half of 2006.

"Taclonex presents an exciting proposition for the treatment of
psoriasis in the U.S., and we are preparing for its launch with great
anticipation," said Roger Boissonneault, CEO of Warner Chilcott.

Psoriasis is a chronic, inflammatory skin disease for which there is no
cure. In plaque psoriasis (psoriasis vulgaris), the most common type,
patches of skin called "lesions" become inflamed and are covered by
silvery white scale. A non-contagious disorder, psoriasis can occur on
any part of the body, and can significantly alter a sufferer's life
both physically and mentally, including the ability to work, play and
interact with others. More than 4.5 million adults in the United States
have been diagnosed with psoriasis, and approximately 150,000 new cases
are diagnosed each year.

Warner Chilcott is a U.S. specialty pharmaceutical company focused on
marketing, developing and manufacturing branded prescription
pharmaceutical products in dermatology and women's healthcare.

SOURCE: Warner Chilcott

randall... is the P news getting better or what?

randall

unread,

Jan 10, 2006, 2:50:16 PM1/10/06

randall wrote:

http://www.israel21c.org/bin/en.jsp?enDispWho=Articles%5El1198&enPage=BlankPage&enDisplay=view&enDispWhat=object&enVersion=0&enZone=Health
<snip>

> Whats fas?
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16400020
> Fas pulls the trigger on psoriasis.

> I suppose we can find more on this later.
>

No time like the present. Biocarta is usually my first visit for these
pathways.

So... to see this pathway in an actual real depiction of a cell,

http://www.biocarta.com/pathfiles/h_fasPathway.asp

Receptors in the TNF receptor family are associated with the induction
of apoptosis, as well as inflammatory signaling. The Fas receptor
(CD95) mediates apoptotic signaling by Fas-ligand expressed on the
surface of other cells. The Fas-FasL interaction plays an important
role in the immune system and lack of this system leads to
autoimmunity, indicating that Fas-mediated apoptosis removes
self-reactive lymphocytes. Fas signaling is also involved in immune
surveillance to remove transformed cells and virus infected cells.
Binding of FAS to oligimerized FasL on another cell activates apoptotic
signaling through a cytoplasmic domain termed the death domain that
interacts with signaling adaptors including FAF, FADD and DAX to
activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are
first activated, to then cleave and activate downstream caspases, and a
variety of cellular substrates that lead to cell death. Caspases cleave
nuclear lamins, causing the nucleus to break down and lose its normal
structure and another caspase substrate is DFF, inducing cleavage and
degradation of the genome. Other caspase substrates are involved in
cytoskeletal structure, cell cycle regulation and signaling pathways.
Activation of JNK kinase, activation of Jun, and production of ceramide
may also play roles in Fas-mediated apoptosis. Activation of
fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and
tumors may escape immune surveillance in part through suppression of
fas-mediated apoptosis using similar mechanisms.

http://www.hprd.org/protein/00609?selectedtab=DISEASES

That other article on lymph cancer and autoimmune links on the same
page one back really goes along well with this.

See the diseases and notice the ALPS links.

And to the TNF disease links,
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637

&
http://www.hprd.org/interactor_map?selectedtab=Fas+Receptor
+
http://www.celldeath.de/encyclo/misc/deathrec.htm
&
http://microvet.arizona.edu/Courses/MIC419/Tutorials/receptorsignaling.html
&
http://www.ihop-net.org/UniPub/iHOP/gs/120945.html

Wow

I wonder if i can find a gut link.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15893696
Increased expression of soluble decoy receptor 3 in acutely inflamed
intestinal epithelia.

Kim S, Fotiadu A, Kotoula V.

Department of Biological Sciences, University of Alabama, Rm 280 Nott
Hall, Tuscaloosa, AL 35487, USA. sk...@bsc.as.ua.edu

Decoy receptor 3 (DcR3), a soluble receptor in the tumor necrosis
factor (TNF) receptor family, is known to inhibit apoptosis mediated by
pro-apoptotic TNF family cytokines such as Fas ligand (FasL), TL1A, and
LIGHT. Therefore, the regulation of DcR3 expression under certain
pathophysiological conditions is of interest since the level of soluble
DcR3 would most likely affect the homeostasis of cells and tissues. We
found that human intestinal epithelial cell (IEC) lines (SW480, SW620,
and HT29) could selectively increase DcR3 release in response to
lipopolysaccharide (LPS) and that all the cells preferentially
expressed Toll-like receptor 4 (TLR-4). LPS-induced DcR3 releases in
IECs appeared to be via the activation of mitogen-activated protein
kinases (MAPK) such as extracellular signal-regulated kinase 1 and 2
(ERK1/2) and c-Jun NH2-terminal protein kinase (JNK), and the
transcription factor NF-kappaB. Moreover, the increased expression of
DcR3 in appendix epithelia from patients with acute appendicitis was
demonstrated. Taken together, the results indicated that DcR3 might
play an important role in the human intestinal epithelium during acute
inflammatory processes caused by endotoxin challenge.

PMID: 15893696

And going back uPstream to the liver.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15570211
Staphylococcal enterotoxin A-induced hepatotoxicity is predominantly
mediated by Fas ligand (CD95L).

Klintman D, Li X, Sato T, Wang Y, Jeppsson B, Thorlacius H.

Department of Surgery, Malmo University Hospital, Lund University,
S-205 02 Malmo, Sweden.

OBJECTIVE: To determine the role of tumor necrosis factor alpha
(TNF-alpha) and Fas ligand (FasL, CD95L) in superantigen-induced and
endotoxin-induced liver injury. SUMMARY BACKGROUND DATA: Gram-positive
bacteria are increasingly common causes of sepsis and multiorgan
failure, but the pathophysiologic mechanisms of superantigen-provoked
hepatotoxicity remain elusive. METHODS: Intravital fluorescence
microscopy was used to study the liver microcirculation in mice
challenged with superantigen (staphylococcal enterotoxin A, SEA) or
endotoxin (lipopolysaccharide, LPS) combined with D-galactosamine.
RESULTS: Administration of 10 microg LPS and 50 microg SEA caused
similar hepatocellular damage as determined by liver enzymes and
apoptosis. Notably, TNF-alpha-deficient mice were completely protected
against hepatic injury provoked by LPS, whereas no protection was
observed in response to SEA. On the other hand, FasL-deficient mice
were protected against liver injury induced by SEA, but no protection
was found when challenged with LPS. LPS increased clear-cut leukocyte
recruitment, whereas SEA had no significant effect on leukocyte
responses in the liver microcirculation. Leukocyte responses to LPS
were decreased by >56% in TNF-alpha gene-targeted animals. Moreover,
antiadhesive therapy, ie, immunoneutralization of P-selectin, which is
an effective inhibitor of leukocyte recruitment, protected against
LPS-induced but not against SEA-induced hepatic damage. CONCLUSIONS:
These novel findings demonstrate that the mechanisms of hepatic injury
in endotoxin-induced and superantigen-induced sepsis are principally
different. On one hand, SEA-provoked hepatotoxicity is mediated by FasL
and is not associated with leukocyte recruitment. On the other hand,
liver damage provoked by LPS is mediated by TNF-alpha and characterized
by prominent leukocyte responses. These data may facilitate development
of more specific therapies against sepsis of different origins.

PMID: 15570211

Would have made more sense on first glance if it had been strep. But
SEA being
commensal does float right under the radar. Its no wonder the
pathogenesis has
been so hard to Pin Point.

Wish I had more time now. Maybe later.

randall.... is this THE year already? The big questions all droP?

randall

unread,

Jan 10, 2006, 10:21:44 PM1/10/06

Hi,

This Fas/FasL/psoriasis thing has me intrigued.

Three posts on this topic on one day! I must be excited.

I had to see who these researchers are.

We can see that Gilhar has been working on Fas/FasL for a long time
here,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pubmed&from_uid=16400020&tool=ExternalSearch

The first and second abstracts has Gilhar working on this since 1996 to
the present.

And here are over 100 abstracts that Gilhar has been involved in,
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Gilhar+A%22%5BAuthor%5D

Lets see him,
http://www.naaf.org/personnel/bio-gilhar.asp

Ok, he looks like the kind of guy who can CURE us!

But can he?

Here's another pic of him and his cohort Dr. Kalish,
http://www.dermatologytimes.com/dermatologytimes/article/articleDetail.jsp?id=37483

Here's another link to FAS and immune conditions
http://www.protein.bio.msu.ru/biokhimiya/contents/v66/abs/66040573.html

<sniP>

The last five chapters describe some manifestations of disturbances in
apoptosis or its individual processes in some immune and inflammatory
diseases such as rheumatoid arthritis, lupus and lupus-like syndromes,
osteoarthritis, psoriasis, and inflammatory renal diseases.

The chapter of P. P. Tak and G. S. Firestein "Apoptosis in rheumatoid
arthritis" focuses on the reaction of T-cells, especially CD4+ cells,
that take part in the immune response of patients with rheumatoid
arthritis. The authors consider that macrophages, fibroblast-like
synoviocytes, and pannocytes can be draw into the inflammation at a
latter stage and play a role in destruction of connective tissue cells
through the induction of apoptosis by cytokines, proteases, and NO.

Apart from the inducers of apoptosis mentioned above, the
Fas/FasL-interaction, perforin/granzyme mechanism, TNFalpha. as well as
oxygen radicals and some transcription factors (c-myc, c-fos, and wild
type of p53) have been implicated in rheumatoid arthritis. The genes
bcl-2 and ras as well as the soluble Fas that compete with Fas of the
cell surface in binding with FasL are seen as anti-apoptotic factors.
The regulation of apoptosis in fibroblast-like synoviocytes and T-cells
is outlined. Therapeutic strategies including gene therapy based on
induction of apoptosis are suggested.

[...]

The chapter of G. G. Song, M. Fleck, J. Wu, H.-C. Hsu, and J. D. Mountz
"Lupus and lupus-like syndromes" discusses genetic defects that
result in defective apoptosis of inflammatory tissue cells in systemic
lupus erythromatosis or lupus-like autoimmune syndromes such as
autoimmune-lymphoproliferative syndrome disease. The authors focus on
the Fas and FasL genes as well as the genes of proteins associated with
Fas such as TNFR1 (tumor necrosis factor receptor type 1) that contain
a death domain or FLICE (interleukin-1beta-converting enzyme). The
mutations in genes of bcl-2 and soluble Fas also receive some
attention.

Evidence concerning other genetic factors that influence apoptosis in
immune system cells (especially in lupus) are presented. Data on
autoimmune antibodies that are raised in response to UV radiation,
viral infections, etc. and serve as apoptosis initiation signals are
summarized in the chapter. The schematic pathways of apoptosis both
under normal conditions and in autoimmune diseases such as systemic
lupus erythromatosis are shown.

The chapter of C. A. Raskin "Psoriasis and apoptosis: a fundamental
analysis of the psoriatic phenotype with clinical and therapeutic
correlations" describes clinical manifestations of this disease and
evidence on genetic predisposition to the disease along with a
triggering role of some environmental factors such as stresses and
infections. The author considers that the histological data point to
altered keratinocyte maturation during their transformation into
corneocytes. The changes are induced by some distortions in programmed
cell death, especially by a discrepancy between expression of inhibitor
of endogenous endonucleases and keratinocyte differentiation. Among the
changes, accelerated proliferation of keratinocytes in psoriasis are
highlighted, this leading to changes in differentiation, pushing
upwards though the epidermis of individual keratinocytes, elimination
of the granular layer, and hyperplasia of psoriasis plaques.
Explanations are provided how the hyperexpression of EGF (epidermal
growth factor) and TGF (transforming growth factor) receptors as well
as aberrant expression of integrins in the suprabasal layer lead to
protection of keratinocytes from apoptosis. The integrins act through
induction of hyperexpression of bcl-xL that to the bcl-2 family is an
inhibitor of apoptosis and is normally expressed in vivo in the basal
layer. It is noted that in psoriasis altered localization of expression
of IGFBP-3 (insulin-like growth factor binding protein-3) that has
intrinsic growth inhibiting properties and leads to terminal
differentiation of cells and could result in the observed hyperplasia
of skin growths. It has been noted that psoriatic keratinocytes appear
to be resistant to IFNgamma (interferon gamma) that could act through
expression of TGF and ICAM-1 (intracellular molecules of cell
adhesion). The production of TNFalpha in psoriasis is indicated through
all epidermal layers while in health this factor is produced only in
the basal layer. The therapeutic effects of UV radiation, cyclosporin
A, derivatives of vitamin D, and glucocorticoids in psoriasis are
discussed in connection with regulatory influences of these factors on
apoptosis in keratinocytes and other epidermal cells including
lymphocytes.

^^^^^^^^^^^^^^^^^^

Fas is CD95. So lets look there as well,

http://ben-may.bsd.uchicago.edu/bmi/faculty/peter/peter.html

randall... this is enough to chew on for a few days

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