Psoriasis support

Author

P News

randall

2005-10-24, 2:03 am

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/...t_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. seonhong@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.bromley@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....

randall

2005-11-12, 1:08 am

Hi,

P news from around the world.

http://seattletimes.nwsource.com/ht...1_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/...t_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/...m.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/...m.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....dbb811182e152ef

randall... hate when that haPPens.

randall

2005-11-12, 1:08 am

randall wrote:

> Now add this one to it,

http://www.signonsandiego.com/union..._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....arch+this+group
And some of us have been successful with ssri's,
http://groups.google.com/group/alt....arch+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....arch+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....arch+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....arch+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[vbcol=seagreen]
>
> 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?
>
>
>
>
> 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>
[vbcol=seagreen]
>
> 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.

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 (XXX) 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 XXX for urea production. Secondly, in most of the
tissues producing NO, citrulline is recycled into arginine via XXX 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 XXX); 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

Could we Pee out the P factors somehow?

Now that wouldn't urea me off?

randall.. it would make me haPPy.

randall

2005-11-20, 5:58 pm

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/...t_uids=16285288
&
http://www.ncbi.nlm.nih.gov/entrez/...t_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=j...sis&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/release...51114220644.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.../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&t...tnG=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/produ...fo/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

2005-11-22, 5:57 pm

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/ne...avins-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/release...51122093217.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=...ish&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/li...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/...0c0005d6780.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/m.../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.Ghoreschi@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...4faa4173eaa06ff

Gosh, i'm only 20-30% sure.

randall... time for a smoothie with frozen banana's

randall

2005-11-26, 5:57 pm

Hi,

The P news was slow and or boring this week.

Abstracts are another story.

http://www.ncbi.nlm.nih.gov/entrez/...t_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/...t_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

2005-12-01, 12:55 pm

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/bnit..._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:
info@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/...-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-...B1-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. zhoumeng66@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

2005-12-10, 12:26 pm

Hi,

P news from around the world.

Here it is,
http://news.google.com/news?lnk=li&...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/...t_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=c...sis&qt_s=Search

Now read this link. Eating carbs does have DNA ramifications
downstream.

http://www.scripps.edu/newsandviews...50509/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...9/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...321/wilson.html and
http://www.scripps.edu/newsandviews...15/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/microb...kaer/tcell.html
http://www.mc.vanderbilt.edu/microb...r/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/...s&list_uids=912

http://www.ncbi.nih.gov/IEB/Researc...db=human&l=CD1D

http://www.dsi.univ-paris5.fr/genat...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.
aggarwal@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.mcinnes@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. Bskurkovich@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

2005-12-14, 5:59 pm

Hi,

P news from around the world:

http://www.eurekalert.org/pub_relea...a-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_relea...u-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

2005-12-18, 6:03 pm

Hi,

P news from the UK.

http://enjoyment.independent.co.uk/...ticle333611.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

[=2E..]

George Melly's Slowing Down (Viking =A317.99) 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/ronni...otts/157/08.htm

I should have been thinking ALL That Jazz

So whats the philip larkin take?

http://www.poetryconnection.net/poe...lip_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

2005-12-20, 12:54 pm

Hi,

P news from around the world.

http://www.medpagetoday.com/Dermato...oriasis/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 =B1 16.0
years, and the mean PASI score was 8.6 =B1 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=B114.6
vs.15.1=B19.4).

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=3D.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

2005-12-20, 5:58 pm

Hi,

New abstract today that looks interesting. As to figuring out pathways.

http://www.ncbi.nlm.nih.gov/entrez/...t_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.carulli@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
i