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Author P News
randall

2006-08-30, 4:31 pm

Hi,

P News from around the world.


Are you in or around Cincinnati? Check this story out.

http://www.wkrc.com/guides/health/h...t_id=3D03229F2=
8-6FB7-4F85-9C08-E3D34A8F4B0E
Breakthrough In Treating Painful Skin Condition

Michael Henry had suffered from psoriasis for many months. The
condition causes a red rash to spread over much of the body. Now,
thanks to a breakthrough in treating psoriasis, Michael is finally
feeling relief. "Literally from like last winter to now it went from
nothing to about 80% of my body." There is no cure for psoriasis, but
two new areas of research are showing promise. The first has to do with
topical agents other than steroids. The second are very precise
targeted therapies. Dr. Pranav Sheth is testing some of these
targeted--or biologic--therapies. "The new biologic therapies
specifically target proteins or cells. Unlike the traditional therapies
that attack all components of the immune system, these are targeted to
specific cells." They appear to help those like Michael Henry to ease
the rash and the pain. "Even, like, lying down for me was hell on
earth, you know" Michael said.

The topical agents being tested for psoriasis Dr. Sheth refers to as
immune modulators. "An immune modulator is an agent that can control a
portion of the immune system without suppressing the whole immune
system," he explained. Some of these are expected to be on the market
as early as next year. Dr. Sheth's team does need patients with
psoriasis who are 16 or 17 years old to help test some of these
treatments. For details, call 513-475-7575. Adults are also needed for
more studies beginning later this fall.

(There is a link for a video on this story-- you need windows media to
run it)

------------------------------------------------------------------------

Are you a diet freak?

Is Atkins for real?

READ this eskimo story some time. It's long and one man's coming to
grip with eating a strictly meat diet. It was printed in Harper's
magazine in
November of 1935.

http://www.biblelife.org/stefansson1.htm


(I read the first page and parts of the third page. Let me know if
the second page is as interesting as the other two.)

-------------------------------------------

Could the TOR gene be worth manipulating? If your prone to diabetes,
maybe
yes!

Now they just need to prove the connections with the fly they found it
in.

http://www.carbwire.com/2006/08/10/...ies_study_expl=
ains_why_atkins_diet_improves_metabolic_syndrome
A new study published in the August 8, 2006 issue of the scientific
journal Cell Metabolism provides further evidence of the health
benefits of the Atkins diet.
Burnham Institute for Medical Research assistant professor Dr. Sean
Oldham found a single gene called TOR in Drosophila fruit flies helps
to regulate vital body regulators such as insulin, glucose and fat
metabolism.
When Dr. Oldham and his research team mutated the TOR gene to see how
it impacted the fruit flies, what they found was a lowering of blood
glucose levels and cholesterol levels as well as a longer lifespan.

What does all of this mean for people who are livin' la vida
low-carb? Well, actually, this is NOT new information for us because we
already knew the Atkins/low-carb approach was an excellent way to
control insulin levels and blood sugar. Dr. Jeff Volek and Dr. Richard
Feinman have already previously "connected the dots" between low-carb
and metabolic syndrome and shared their discovery last year. It's nice
to know other researchers are finally catching up to this well-known
fact!

Despite this amazing discovery about how metabolic syndrome can be
treated naturally through a healthy low-carb diet, you are never going
to guess what the researchers are proposing to do in response to their
study. Click here (**) to read what they have planned and more on this
study that is yet another piece of scientific vindication for the late
great Dr. Robert C. Atkins.
(**)
http://livinlavidalocarb.blogspot.c...ains-why-atkin=
s-diet.html

Some folks do really well with atkins plan. But wave one chunk of sour
dough bread
and their off the program like an alcoholic headed for a binge.

Carbism and carbaholics are another genectic problem with this TOR gene
revelation. They have a long way to go. As with psoriatic genes it's no
walk in the park.

------------------------------------------------------------

If the above is beyond your will power. Try some softer advice.

http://www.chron.com/disp/story.mpl/life/4144759.html

Diet and exercise still important part of health regimen


BY JOE GRAEDON and TERESA GRAEDON
King Features Syndicate

A few years ago, diet and exercise were considered crucial cornerstones
of a heart-healthy lifestyle. Now, drugs seem to have replaced
willpower and fitness.
We recently received an e-mail that epitomizes this mind-set: "Is it
necessary to watch your diet and exercise when you are taking Lipitor,
or will Lipitor be effective all by itself?"
If you read the official prescribing information for Lipitor, you will
discover, "Lipid-altering agents should be used in addition to a diet
restricted in saturated fat and cholesterol only when the response to
diet and other nonpharmacological measures have been inadequate."
What that means in ordinary English is that people should watch their
diet first and maintain prudent, low-fat eating habits even while they
are taking Lipitor and related cholesterol-lowering drugs.
That's the theory. In practice, though, people learn quite quickly that
statin-type medications such as Crestor, Lipitor, Pravachol and Zocor
(now available generically as simvastatin) are so effective that they
don't have to fret about dietary indiscretions.
One person we know found that by taking Lipitor he could enjoy baked
brie without worry. Other folks relish steak and a baked potato with
sour cream, while those with a sweet tooth find that cheesecake is
still on the menu as long as they take their medicine.
It doesn't take people long to realize that they can cheat on their
diets and still have fabulous results when they get their blood test
back. If they can eat burgers, fries and shakes and still have low
cholesterol, why not indulge?
The problem with this approach is that cholesterol is only one
contributor to heart disease. There are more than 240 other risk
factors. A high-fat diet may increase inflammation, for example, and
bring on other problems.
Statin-type drugs are not without cost, both financially and
physically. Some people cannot tolerate the muscle pain and weakness
that may accompany statins. Other side effects may include memory
problems, nerve damage, sexual difficulties and joint pain.
Some people cannot get their cholesterol under control no matter how
careful they are with diet and other lifestyle changes. But many people
can be successful at reducing their risks by taking several crucial
steps:
=B7 Cut back on carbs, especially refined flour and sugar. They raise
triglycerides.
=B7 Go for fiber. Psyllium can lower cholesterol. So can vegetables
rich in soluble fiber.
=B7 Include nuts such as almonds or walnuts in the diet. They lower
cholesterol and reduce the risk of heart disease.
=B7 Ditch trans fats. Use olive oil instead.
=B7 Eat fish and/or take fish oil.
=B7 Ask your doctor about niacin or red yeast rice. The B vitamin can
lower cholesterol. So can the dietary supplement, which contains
natural statin compounds.
=B7 Exercise.
Readers who would like more information on natural approaches to
cholesterol control may find helpful information in our book "The
People's Pharmacy Guide to Home and Herbal Remedies." It can be
purchased at your local bookstore or from our Web site:
www.peoplespharmacy.com.
Statin drugs can save lives. But they should not take the place of a
prudent diet and healthy lifestyle.
THE PEOPLE'S PHARMACY
Q=2E You've had several suggestions about remedies for plantar warts. I
had one on each foot when I was a kid in the late 1950s. They were
removed with two sessions of spot radiation. The radiation was on the
same wart each time, and a week or so later, the wart cone fell out and
the hole shrank. It was totally painless.
A=2E During the first half of the 20th century, dermatologists used
X-rays to treat a wide variety of skin conditions. Not only was
radiation used against plantar warts, it was also employed in the
treatment of psoriasis, eczema and fungal infections of the skin.
This type of treatment would be considered reckless today. Skin cancers
sometimes developed at the site that was irradiated. There are now much
safer treatments available against warts.
Q=2E I have a caution about Effexor, which I took for hot flashes. I had
to go out of town suddenly and ran out of pills because I couldn't get
the prescription refilled beforehand. On the third day without it, I
started to feel bad. Then I began vomiting and shaking.
As soon as I returned home, I took some anti-nausea medicine and
restarted the Effexor. The next day I felt fine, so it wasn't the flu.
I tapered off the medication over the next several months without any
problems. My doctor said she had never heard of this type of reaction,
but I know that's what it was.
A=2E Many people have difficulties with symptoms of withdrawal when they
discontinue an antidepressant like Effexor suddenly. It makes no
difference whether you intend to stop the drug, or whether you forget
your dose; nausea, vomiting, dizziness, sweating, shakiness, shocklike
electrical sensations and anxiety are possible symptoms.
Your approach of gradually tapering the dose is sensible. We are always
discouraged to learn that a doctor is unfamiliar with this reaction,
since it has been known and documented for at least 10 years.
Our Guides to Antidepressant Pros and Cons and Psychological Side
Effects provide more insight on such problems and solutions for
stopping. Anyone who would like copies, please send $2 in check or
money order with a long (No. 10), stamped (63 cents), self-addressed
envelope to: Graedons' People's Pharmacy, No. MX-23, P.O. Box 52027,
Durham, NC 27717-2027.
Q=2E My doctor recently switched me from the cholesterol-lowering drug
Lipitor to Omacor after I had a slightly elevated liver count. What
should I know about Omacor?
A=2E Omacor is highly purified prescription fish oil. The Food and Drug
Administration approved its use to lower high triglycerides. The most
common side effects of Omacor are burping or indigestion, but they are
less likely with this prescription product than with everyday fish oil.
Q=2E I am responding to a question from a person who is going on a cruise
and doesn't want to get seasick. Suggest Bonine. This tiny pink pill is
available over the counter.
It should be taken an hour before boarding the ship, or you can chew
the tablet as soon as you remember it. The only side effect is a
slightly dry mouth. I went on a cruise to Hawaii and never got sick.
Bonine was my miracle tablet.
A=2E Meclizine is available over the counter as Bonine or by prescription
as Antivert. This antihistamine has been used for motion sickness for
decades. Some people experience drowsiness, dry mouth, constipation,
urinary retention or blurred vision.
THE PEOPLE'S HERBAL PHARMACY
Q=2E I live in a very tropical, hot and humid place. For the past year, I
have had recurring yeast infections. My problem is not so much the
yeast infection (which I think I now have under control, having taken a
series of fluconazole pills and ingested quantities of yogurt and
acidophilus), but rather the "jock itch" that has remained.
I have used nystatin with zinc (it seems to stay on well) and Lotrimin.
I am on a no-underwear, skirts-only clothing routine. Do you have any
other suggestions?
A=2E You may find this bizarre, but men have told us that applying
Listerine to the groin area can help control jock itch. This
old-fashioned yellow mouthwash contains 26.9 percent alcohol plus the
herbal oils eucalyptol, menthol, methyl salicylate and thymol.
These oils have antifungal activity, especially in concert. Be careful
how you apply it, though. The alcohol and other ingredients might sting
if the Listerine lands where it doesn't belong.
Q=2E After months of using Nexium for stomach ulcers with little relief,
I started using DGL licorice, two or three pills before meals and at
bedtime. I felt better within days. Have you ever heard of this?
A=2E DGL is short for deglycyrrhizinated licorice. This is an extract of
the licorice root with one active ingredient, glycyrrhizin, removed.
This specially treated licorice has long been used to treat ulcers. In
one study, it proved as effective as cimetidine (Tagamet) for this
purpose (Gut, June 1982). This particular form of licorice is less
likely to cause the complications (fluid retention, potassium loss,
hypertension) associated with regular black licorice.
Q=2E I am interested in trying the gin-soaked raisins for joint pain, but
I have a question about the safety of eating the raisins and taking
anti-anxiety medication. Is it safe to eat nine raisins and take Xanax
the same day? I have to take Xanax sometimes and have read that alcohol
should not be used while taking it.
A=2E You are absolutely right that alcohol and sedatives like Xanax
(alprazolam) do not mix. We had the alcohol content of nine gin-soaked
raisins analyzed and learned that it amounts to about one drop. That
should not be enough to cause problems, even when you need to take
Xanax.
Anyone who would like more information about the "Raisin Remedy" may
wish to order our Guide to Home Remedies. Please send $2 in check or
money order with a long (No. 10), stamped (63 cents), self-addressed
envelope to: Graedons' People's Pharmacy, No. R-1, P.O. Box 52027,
Durham, NC 27717-2027. It can also be downloaded for $2 from our Web
site: www.peoplespharmacy.com.
Q=2E Shortly after I read about using toothpaste for fire-ant bites, I
was bitten by a fire ant. I started spreading toothpaste twice a day
over my swollen ankle. It has been three days, and the inflammation has
mostly gone away. I only have a small red area around the center of the
bite. Normally, I would have been in the doctor's office receiving
antibiotics by now. Additionally, the toothpaste helped greatly with
the itch.
A=2E Readers have applied many remedies to fire-ant bites. In addition to
toothpaste, they report success with tobacco juice, Vicks VapoRub,
Listerine, apple-cider vinegar or meat tenderizer mixed into a paste
with water.

www.PeoplesPharmacy.com


---------------------------------------------------------------


randall...one droP of gin in 9 raisins!

randall

2006-09-05, 4:30 pm

Hi,

P News

J's post still has me thinking. So does Drea's for that matter.

The link to that think,
http://www.ncbi.nlm.nih.gov/entrez/...nf+sb203580+lps


Certainly brings up many current threads for villains and inflammation.
(HO-1, Caveolin-1, and even leptin as a bad guy if you have lps)

Most of them related to Ros in one way or another.

Is it all simple Ros or not? And is it simple?


http://www.ncbi.nlm.nih.gov/entrez/...l=pubmed_docsum
Oxidative stress in allergic and inflammatory skin diseases.

* Okayama Y.

Research Center for Allergy and Immunology, RIKEN Yokohama Institute,
Yokohama, Japan. yokayama @rcai.riken.go.jp

The skin is exposed to endogenous and environmental pro-oxidant agents,
leading to the harmful generation of reactive oxygen species (ROS). The
resulting oxidative stress damages proteins, lipids, and DNA. An
imbalance between ROS and antioxidants can lead to an elevated
oxidative stress level. Some evidence indicates that allergic and
inflammatory skin diseases like atopic dermatitis, urticaria and
psoriasis are mediated by oxidative stress. For example, monocytes from
patients with atopic dermatitis are primed to generate ROS in response
to zymosan, a Toll-like receptor 2 (TLR2) ligand, suggesting that
Staphylococcus aureus may damage lesional skin of the disease by
production of ROS. Mast cells generate mainly intracellular ROS
following the aggregation of FceRI; these ROS may act as secondary
messengers in the induction of several biological responses. The
present review summarizes the involvement of ROS in the pathogenesis of
allergic and inflammatory skin diseases.

PMID: 16127829


http://www.ncbi.nlm.nih.gov/entrez/...t_uids=14761133

Antioxidant activity, lipid peroxidation and skin diseases. What's new.

* Briganti S,
* Picardo M.

Cutaneous Physiopathology Laboratory, San Gallicano Dermatological
Institute, 25/A Via S. Gallicano, 00153-Rome, Italy. fisiolab @ifo.it


Due to its interface function between the body and the environment,
the skin is chronically exposed to both endogenous and environmental
pro-oxidant agents, leading to the harmful generation of reactive
oxygen species (ROS). There is compelling evidence that oxidative
stress is involved in the damage of cellular constituents, such as DNA,
cell membrane lipids or proteins. To protect the skin against the
over-load of oxidant species, it contains a well-organised system of
both chemical and enzymatic antioxidant which are able to work in a
synergistic manner. Skin antioxidant network protects cells against
oxidative injury and prevent the production of oxidation products, such
as 4-hydroxy-2-nonenal or malonaldehyde, which are able to induce
protein damage, apoptosis or release of pro-inflammatory mediators,
such as cytokines. When oxidative stress overwhelms the skin
antioxidant capacity the subsequent modification of cellular redox
apparatus leads to an alteration of cell homeostasis and a generation
of degenerative processes. Topical application or oral administration
of antioxidants has been recently suggested as preventive therapy for
skin photoaging and UV-induced cancer. The recognition that ROS can act
as second messengers in the induction of several biological responses,
such as the ___activation of ______NF-kB or AP-1,_____ the generation
of cytokines, the modulation of signalling pathways, etc., has led many
researchers to focus on the possible effects of antioxidants in many
pathological processes. The recent demonstration that the peroxisome
proliferators-activated receptors, whose natural ligands are
polyunsaturated fatty acids and theirs oxidation products, have a
central role in the induction of some skin diseases, such as psoriasis
or acne, has indicated new links between free radicals and skin
inflammation. Based on these findings, the review summarises the
possible correlations between antioxidant imbalance, lipid oxidative
breakage and skin diseases, from both a pathological and therapeutic
points of view.


PMID: 14761133


==============================================

http://groups.google.com/group/alt....+oxygen+species

The iron google brings back hepcidin,
http://groups.google.com/groups/sea...sis&qt_s=Search

Here's a good one,
http://www.eurekalert.org/pub_relea...--uau102504.php
&
http://www.knowledgeofhealth.com/re...on,%20Chelation

Bringing back hemochromatosis.

http://www.ncbi.nlm.nih.gov/entrez/...l=pubmed_docsum
STAT-3 mediates hepatic hepcidin expression and its inflammatory
stimulation.

* Verga Falzacappa MV,
* Vujic Spasic M,
* Kessler R,
* Stolte J,
* Hentze MW,
* Muckenthaler MU.

MMPU/Department of Pediatric Oncology, Hematology and Immunology,
University of Heidelberg, Germany.
Hepcidin is a key iron-regulatory hormone produced by the liver.
Inappropriately low hepcidin levels cause iron overload, while
increased hepcidin expression plays an important role in the anaemia of
inflammation (AI) by restricting intestinal iron absorption and
macrophage iron release. Its expression is modulated in response to
body iron stores, hypoxia, inflammatory and infectious stimuli,
involving at least in part cytokines secreted by macrophages. In this
study we established and characterized IL-6-mediated hepcidin
activation in the human liver cell line Huh7. We show that the proximal
165bp of the hepcidin promoter are critical for hepcidin activation in
response to exogenously administered IL-6 or to conditioned medium from
the monocyte/macrophage cell line THP-1. Importantly, we show that
hepcidin activation by these stimuli requires a STAT-3 binding motif
located at position -64/-72 of the promoter. The same STAT binding site
is also required for high basal level hepcidin mRNA expression under
control culture conditions, and siRNA-mediated RNA knock-down of STAT-3
strongly reduces hepcidin mRNA expression. These results identify a
missing link in the acute phase activation of hepcidin and establish
STAT-3 as a key effector of baseline hepcidin expression and during
inflammatory conditions.

PMID: 16946298

http://www.naturalhealthlibrarian.c...rontimebomb.asp

Is there an iron time bomb for some psoriatics? All of us, if only, in
some of the pathways?

Or a simple hair trigger as the result of P DNA and evolution of time
and place (enviroment) leading to the condition called psoriasis?

Is it all to compensate for ROS?

I wonder as the facts are known day by day.

--------------------------------------------------

Exercise, meditation, good food should keep you from feeling down and
singing the P blues.

So? Get haPPy already or else!

http://news.biocompare.com/newsstory.asp?id=149346
Depressed Patients Experience Excessive Inflammation During Stressful
Situations
8/31/2006

Source: Emory university Health Sciences Center


Individuals with major depression have an exaggerated inflammatory
response to psychological stress compared to those who do not suffer
from depression, according to a study by researchers at Emory
University School of Medicine. Because an overactive inflammatory
response may contribute to a number of medical disorders as well as to
depression, the findings suggest that increased inflammatory responses
to stress in depressed patients may be a link between depression and
other diseases, including heart disease, as well as contributing to
depression itself.

Results of the study, led by Andrew Miller, MD, and Christine Heim,
PhD, of Emory's Department of Psychiatry and Behavioral Sciences, are
published in the Sept. 1 issue of the American Journal of Psychiatry.

"Several examples of increased resting inflammation in depressed
patients already exist in the literature, but this is the first time
anyone has shown evidence to suggest that the inflammatory response to
stress may be greater in depressed people," says Dr. Miller.

The study included 28 medically healthy male participants, half of whom
were diagnosed with major depression and half of whom were not
depressed. The participants were exposed to two moderately stressful
situations during a 20-minute time period. Blood was collected every 15
minutes starting immediately before and then up to an hour and a half
after the test to check for key indicators of inflammation. The
researchers measured levels of a pro-inflammatory cytokine (a
regulatory protein secreted by the immune system) called interleukin-6,
and the activity of a pro-inflammatory signaling molecule in white
blood cells called nuclear factor-kB.

While at rest (before the stress challenge), the depressed patients had
increased inflammation relative to the control group. Both the
depressed and the healthy groups showed an inflammatory response to the
stress challenge, but people who were currently depressed exhibited the
greatest increases of interleukin-6 and nuclear factor-kB.

"While inflammation is essential for us to fight bacterial and viral
infections, too much inflammation can cause harm," says Dr. Miller.
"There's always some collateral damage when the immune system gets
fired up, and we now believe that too much inflammation, either at rest
or during stress, may predispose people to become depressed or stay
depressed." In addition, medical research over the last decade has
shown that runaway inflammation may play a role in a number of
disorders, including heart disease, cancer, and diabetes, all of which
have been associated with depression.
<sniP>

-------------------------------------------------

So you want to turn off your T cells to stop P?

Go in to outer space!
http://news.biocompare.com/newsstory.asp?id=149151

Astronauts may need to learn a trick or two from psoriatics
to keep their immune systems on guard in outer space.
------------------------------------------------------

randall... I lost half this post.. i'll find it later.

randall

2006-09-06, 2:26 am

Hi,

P News


Large psoriasis donation made.
http://www.newsnet5.com/health/9790423/detail.html

University Hospitals Gets $5M Gift For Psoriasis Research


CLEVELAND -- university Hospitals of Cleveland Tuesday announced a $5
million gift for research and treatment of the skin disease psoriasis.
The gift comes from the Murdough Foundation, whose President Thomas
Murdough Jr. founded the toy companies Little Tykes and Step-Two.
Murdough also serves as a university Hospitals trustee. Murdough said
the goal is to make university Hospitals a world leader in psoriasis.
Psoriasis victims suffer from sometimes severe cases of itchy, inflamed
skin.According to a university Hospitals press release, the gift is the
largest known in the U.S. for dermatology at an academic medical
center. An estimated 6 million Americans suffer from psoriasis.

--------------------------------------------------------

Update on the hh pathway.


http://www.signaling-gateway.org/up...09/nrg1955.html

What vitamins can do for hedgehog

Vitamin D3 contributes to silencing the hedgehog signaling pathway in
the absence of ligand.

The hedgehog (HH) pathway ranks high in the league of important
developmental pathways, yet the mechanics of HH signalling are still
sketchy. Now, a study that pulls together evidence from genetic
mutants, cell culture experiments and human disease phenotypes has
concluded that vitamin D3 (or its precursor) is what keeps the pathway
silenced in the absence of the HH ligand, and that it does so
non-cell-autonomously.


The HH pathway is highly conserved and also highly unusual: for
example, there are two receptors involved, Patched1 (PTCH1) and
Smoothened (SMO). These two transmembrane proteins have different
functions, with PTCH1 inhibiting SMO constitutively; binding of HH to
PTCH1 relieves this inhibition and allows the transcription of
downstream genes, including glioma associated (Gli). What precisely
goes on between PTCH1 and SMO was the focus of the current study, which
made use of a culture of mouse fibroblasts in which activation of the
HH pathway was monitored by a Gli-reporter gene.

The first question to be asked by Maarten Bijlsma and colleagues was
about the cell autonomy of the effect of PTCH1 on SMO. They show that
HH signalling in cells that were constitutively activated by SMO was
silenced if PTCH1-overexpressing cells were also present. This and
other evidence indicated that the effect of PTCH1 is
non-cell-autonomous and that it involves an intermediary molecule.
Because the inhibiting effect was not visible when a PTCH1-exposed but
serum-free medium was used, the authors then suggested that the
inhibitory intermediary must be transported by a lipoprotein (which is
absent from serum-free media). But what could the intermediary be?

A clue came from humans who suffer from decreased HH signalling -
these individuals have high levels of a hydroxysteroid,
7-dehydrocholesterol (7-DHC). This molecule was indeed shown to inhibit
SMO, and the effect was also seen in vivo by exposing zebrafish embryos
to the 7-DHC derivative vitamin D3. The fact that PTCH1 looks like a
pump means that the pieces of the puzzle can be put into place. PTCH1
normally pumps out vitamin D3 (or its precursor) from the cell, which
then inhibits SMO in cells nearby. When HH comes along and binds to
PTCH1, the pump shuts down, and SMO is free to activate the
intracellular HH pathway.

This neat story has ramifications beyond the understanding of animal
development. By acting non-cell-autonomously, PTCH1 could exert a
tumour-suppressor function on surrounding PTCH1-inactivated (that is,
HH-pathway hyperactive) cells, and so manipulating the expression of
wild-type PTCH1 could represent a fruitful avenue for cancer therapy.

----------------------------------

Fungal pathway for P? More light,

http://www.signaling-gateway.org/up...09/nri1928.html
Pick a CARD

Caspase-recruitment-domain protein 9 (CARD9) is involved in a novel
non-TLR-dependent signaling pathway required for antifungal innate
immunity

The innate immune system of vertebrates detects pathogenic organisms by
recognizing the molecular patterns typical of microbial components.
Toll-like receptors (TLRs) constitute a major class of
pattern-recognition receptors (PRRs), but other PRRs are also important
for the recognition of certain pathogens. However, the way in which
these PRRs trigger inflammatory pathways is not well understood. A
recent study of the poorly characterized protein
caspase-recruitment-domain protein 9 (CARD9) has helped to delineate a
novel non-TLR-dependent signalling pathway involved in antifungal
innate immunity.

CARD9 is structurally related to CARD-MAGUK (membrane-associated
guanylate kinase) protein 1 (CARMA1). CARMA1 mediates nuclear
factor-kappaB (NF-kappaB) activation through BCL-10 (B-cell lymphoma
10) and MALT1 (mucosa-associated-lymphoid-tissue lymphoma-translocation
gene 1) in response to the activation of T- and B-cell receptors. CARD9
can bind BCL-10 but lacks other regions that are typical of
CARMA-family members involved in NF-kappaB activation. Given these
characteristics, it was thought that CARD9 might interfere with the
interaction between CARMA1 and BCL-10.

Gross et al., however, found that T- and B-cell function in
CARD9-deficient mice resembled that of wild-type mice, and they
concluded that CARD9 was probably not involved in receptor signalling
through the CARMA1-BCL-10 pathway. When the authors compared the
responses of bone-marrow-derived dendritic cells (BMDCs) from
CARD9-deficient mice and wild-type mice, they discovered that cytokine
production induced by zymosan (a cell-wall component of yeast) or by
whole fungal cells of Candida albicans was severely impaired in the
absence of CARD9. This signalling pathway selectively involved
dectin-1, the main mammalian PRR for zymosan, rather than TLR2, which
also binds zymosan. Co-expression of CARD9 and BCL-10 showed that these
signalling molecules cooperate to induce NF-kappaB activation.
Additional studies indicated that BCL-10 and MALT1 are both required
for zymosan-induced activation of BMDCs.

The data indicate that CARD9 is an essential link in a newly defined
TLR-independent signalling pathway that links zymosan-activated
dectin-1 and BCL-10-MALT1-mediated activation of NF-kappaB. CARD9
therefore has a role in innate immunity that is analogous to the role
of CARMA1 in adaptive immunity.

--------------------------------------

http://www.nature.com/ni/journal/v7/n9/abs/ni1367.html

The Ubc13 E2 ubiquitin-conjugating enzyme is key in the process of
'tagging' target proteins with lysine 63-linked polyubiquitin chains,
which are essential for the transmission of immune receptor signals
culminating in activation of the transcription factor NF-kappaB. Here
we demonstrate that conditional ablation of Ubc13 resulted in defective
B cell development and in impaired B cell and macrophage activation. In
response to all tested stimuli except tumor necrosis factor,
Ubc13-deficient cells showed almost normal NF-kappaB activation but
considerably impaired activation of mitogen-activated protein kinase.
Ubc13-induced activation of mitogen-activated protein kinase required,
at least in part, ubiquitination of the adaptor protein IKKbold gamma.
These results show that Ubc13 is key in the mammalian immune response.


----------------------------------



randall... might not be that simple?

randall

2006-09-08, 4:28 pm

Hi,


P news



http://www.eurekalert.org/pub_relea...ki-cc090806.php

'Allergy cells' can aggravate cancer and psoriasis

The body's mast cells are mainly associated with allergic reaction in
the way they release histamine and other inflammatory substances.
However, researchers at Karolinska Institutet have now demonstrated how
the mast cells can also contribute to diseases like psoriasis and
cancer.

Mast cells are most known for their association with allergic
reactions, as they act like microscopic "bombs" to trigger the release
of a number of substances that give rise to the classic allergic
symptoms, such as swelling, congestion and itching. The explosive
reactions are activated when an allergen (such as pollen particles)
binds to receptors on the surface of the mast cell, which then opens
and secretes part of its contents.

In the past few years it has emerged that mast cells, which are a type
of immune cell, are probably also involved in the development of a
number of other diseases, like atopical eczema, psoriasis, and the
Hodgkins lymphoma cancer type. These diseases are characterised by
chronic inflammations and an increase in the number of mast cells.
However, the mechanisms behind this are relatively unknown.

Associate professor Gunner Nilsson at Karolinska Institutet and his
research group have now found a possible explanation for the link
between mast cells and several non-allergic diseases. The study, which
is presented online by The Journal of Clinical Investigation, shows
that mast cells can be activated in a previously unknown way that might
lead to chronic inflammation.

"These new findings contribute to our understanding of the part played
by the mast cell in atopical eczema, psoriasis and Hodgkins Lymphoma,"
says Mr Nilsson. "We hope that our research will make it possible for
scientists to develop new forms of therapy for the mast cell-related
diseases."

The group discovered that the CD30 protein, which is found on the
surface of the immune systems T-lymphocytes amongst other places, can
stimulate mast cells to release proteins that regulate the recruitment
of inflammatory cells. Since it is already known that levels of CD30
are higher in people with psoriasis or atopical eczema and with
Hodgkins lymphoma, the results can explain how the mast cells are
activated and how they aggravate inflammation in these diseases.

###

Publication:

"Mast cell CD30 ligand is upregulated in cutaneous inflammation and
mediates degranulation-independent chemokine secretion"

Marie Fischer, Ilkka Harvima, Ricardo Carvalho, Christine M=F6ller,
Anita Naukkarinen, Gunilla Enblad and Gunnar Nilsson.

The Journal of Clinical Investigation, Online 7 September 2006, October
Issue 2006

----

I'll be sure to get this article once it's available. Their online site
cuts off
the day before 7 sept.

For the time being, a search of pubmed for mast cells and P may help.

http://www.ncbi.nlm.nih.gov/entrez/...pmax=3D100&ter=
m=3D%20mast+cell*+psoria*

Let's search for LPS and drop KW psoriasis,
http://www.ncbi.nlm.nih.gov/entrez/...pmax=3D100&ter=
m=3D%20mast+cell*+lps

The second hit seems productive.
http://www.ncbi.nlm.nih.gov/entrez/...=3DRetrieve&do=
pt=3DAbstractPlus&list_uids=3D16920486&query_hl=3D15&itool=3Dpubmed_docsum
The mast cell mediator PGD(2) suppresses IL-12 release by dendritic
cells leading to Th2 polarized immune responses in vivo.

* Theiner G,
* Gessner A,
* Lutz MB.

Department of Dermatology, university of Erlangen-Nuremberg, Erlangen,
Germany.

Dendritic cells (DC) and mast cells (MC) are colocalized in superficial
organs such as the skin. Both cell types recognize and respond to
pathogens. DC capture and transport antigens to the draining lymph node
for CD4(+) T cell priming and T helper 1 (Th1) or Th2 polarization. As
MC are mainly associated with Th2 responses, DC-MC interactions may
favor Th2 priming by DC. Here, we show the role of different MC
mediators on IL-12 and IL-10 production by DC. While histamine,
leukotriene C4, heparin and chondroitin sulfate A had little and
unspecific effects on the cytokine production, prostaglandin D(2)
(PGD(2)) downregulated IL-10, IL-12p70 and p40. After subcutaneous
(s.c.) injection of ovalbumin (OVA)-loaded, lipopolysaccharide
(LPS)-matured DC into Th1-prone C57BL/6 mice, the levels of IFN-gamma
produced by Th1 cells were decreased while IL-4 production remained
low. When TNF-matured DC were pretreated with PGD(2), loaded with the
endotoxin-free antigen KLH and injected s.c. into Th2-prone BALB/c
mice, we found a dose- and time-dependent upregulation of IL-4 and
downregulation of IFN-gamma by T cells. Together, MC-derived PGD(2)
instructs DC to polarize CD4(+) T cells towards Th2 responses. As a
consequence, such a DC-MC cooperation may contribute to the maintenance
of Th2 responses in allergic patients.

PMID: 16920486

As far as P goes, allergey may agravate but doesn't cause psoriasis.

For some of us, removal of allergens may give a high degree of
clearing. But how high is
based on cutting out your allergens from YOUR diet and enviroment.

Not a small F=EAte. Not to mention finding a few hundred psoriatic folks
to do the
testing would hardly be worth the efforts of anyone without the $ to
blow. What are you going to prove?

OTOH simply using psoriasis groups to poll for allergies is
illustrative
of the Th1/Th2 skews and brings up sebopsoriasis and areas germane
to atopy and psoriasis.

---------------------------------------------------

Gene methylation has been a topic here,
http://groups.google.com/groups/sea...psoriasis&qt_s=
=3DSearch

H'mmm that first hit had me chagrined a tad bit.

Oh well, this is an area riPe for exploration.

News,


http://news-info.wustl.edu/tips/page/normal/7538.html

Pathway toward gene silencing described in plants

Get shorty

By Tony Fitzpatrick

Sept. 7, 2006 -- Biologists at Washington university in St. Louis have
made an important breakthrough in understanding a pathway plant cells
take to silence unwanted or extra genes using short bits of RNA.
Basically, they have made it possible to see where, and how, the events
in the pathway unfold within the cell, and seeing is believing, as the
old saying goes.

Craig Pikaard, Ph.D., Washington university professor of biology in
Arts & Sciences and his collaborators have described the roles that
eight proteins in Arabidopsis plants play in a pathway that brings
about DNA methylation, an epigenetic function that involves a chemical
modification of cytosine, one of the four chemical subunits of DNA.
Without proper DNA methylation, higher organisms from plants to humans
have a host of developmental problems, from dwarfing in plants to
certain tumors in humans, and death in mice. One role of DNA
methylation is to turn off repetitive genes, such as transposable
elements that can move or spread throughout a genome and disrupt other
gene functions if left unchecked. <sniP>

-----------------------------------------------


Targeting only the cells you suspect is near at hand! Targeting the dna
in
that cell will be a major couP.

http://www.pharmalive.com/News/inde...categoryid=3D15

Researcher Lights the Way to Better Drug Delivery

Note to Journalists: Publication quality photos are available at

http://news.uns.purdue.edu/images/+...endocytosis.jpg and
http://news.uns.purdue.edu/images/+...ndocytosis2.jpg


WEST LAFAYETTE, Ind., Sept. 8, 2006--A Purdue university researcher has
explained for the first time the details of how drugs are released
within a cancer cell, improving the ability to deliver drugs to a
specific target without affecting surrounding cells.

"As a general strategy, the indiscriminate delivery of drugs into every
cell of the body for the treatment of a few specific pathologic cells,
such as cancer cells, is a thing of the past," said Philip Low, the
Ralph C. Corley Distinguished Professor of Chemistry. "Most new drugs
under development will be targeted directly to the pathologic,
disease-causing cells, and we have shed light on the details of one
mechanism by which this is achieved."

An understanding of the cellular process that leads to the release of
targeted drugs is a major advancement for the field, he said.

"This will help others interested in targeted drug therapy," said Low,
who also is founder and chief science officer of Endocyte Inc., a
Purdue Research Park-based company. "The knowledge applies not only to
the treatment of cancer. The understanding of how to deliver and unload
a cancer drug can be extrapolated to all sorts of other diseased cells.
The uptake pathways are similar in cells involved in arthritis,
multiple sclerosis, psoriasis and Crohn's disease."

Interest in how drugs are released after they enter their targeted cell
led Low and his team to develop a color-coded method to visualize the
cellular mechanisms. Jun Yang, a postdoctoral research associate in
Low's research group, together with Ji-Xin Cheng, an assistant
professor in the Department of Biomedical Engineering, and his graduate
student Hongtao Cheng, developed this method using a technique called
fluorescence resonance energy transfer imaging.

"The drug turns from red to green when it is released inside the cell,
clearly illuminating the process," Yang said. "This is the first
optical method to be developed to monitor this release. The main
promise of this method is that it does not damage the cells being
studied. Therefore, we are able to observe the process under true
physiological conditions and watch it right as it is happening."

This research, funded by Endocyte, will be detailed in a paper in
Tuesday's (Sept. 12) issue of the Proceedings of the National Academy
of Sciences and is currently available online.

In targeted drug therapy, drugs are linked to molecules that are used
in excess by pathologic cells, for example a required nutrient, in
order to transport drugs directly to the targeted cells while avoiding
significant delivery of the toxic drug to normal cells. A commonly used
agent, referred to as a ligand, is the vitamin folic acid. Cancer cells
need folic acid to grow and divide and, therefore, have developed
abundant receptors to capture it. These receptors are largely absent in
normal cells. This means folic acid, and the drug linked to it, are
attracted to the pathologic cells and are harmless to healthy cells,
Low said.

Low led the team that discovered this folate-targeted treatment method
in 1991 and the receptor-targeted technology is proprietary to
Endocyte.

"It is desirable to have the drug released from the ligand, folic acid,
once the folate-linked complex enters the cell," Yang said. "This
'conditional drug release' is usually realized by attaching folate to
the drug through a linker that falls apart inside the cell. There were
several linkers in common use, but with mixed efficiency. In this study
we undertook to interrogate the full details of this breakdown
process."

Yang examined receptor endocytosis, the process by which cells absorb
materials - such as a drug attached to folic acid - that have been
captured at special sites, called receptors, on the cell surface. The
compound is then broken down and processed, releasing the drug.

One of the key mechanisms of this breakdown is disulfide reduction,
which involves the breaking of chemical bonds. It was thought that
disulfide reduction relied on the movement of the material along
microtubules, hollow tubelike structures, and fusion with special
digestive-enzyme containing compartments within the cell called
lysosomes. However, the research showed that disulfide reduction
occurred even when such components were removed from the process.

By inactivating different cellular components, Yang discovered which
components are essential to the disulfide reduction process.

"It was surprising to learn that many other components of the cell,
aside from those previously assumed to be responsible, were capable of
releasing the drug from folic acid," Yang said. "This significantly
increases the opportunity for the drug to be released. For instance, we
used to believe it had to get to a specific location to be released,
and now we know it can happen almost anywhere during endocytosis."

The mechanisms, locations and cellular components involved in the
release of drugs within a cell had been under debate for several years,
Low said.

"This is the definitive statement on how drugs are released within a
cell," he said. "We will use this knowledge to develop better
receptor-targeted drug therapies to treat cancer and other diseases."

Low and Yang worked with scientists from the Department of Chemistry,
Weldon School of Biomedical Engineering and Endocyte, and used
facilities at the Oncological Sciences Center, part of the Purdue
Cancer Center, and Bindley Bioscience Center at Purdue's Discovery
Park.

Endocyte Inc. develops receptor-targeted therapeutics for the treatment
of cancer and autoimmune diseases. Endocyte has three compounds in Food
and Drug Administration-regulated clinical trials: EC20, a targeted
diagnostic agent that is in Phase II studies; EC17, a targeted-hapten
therapy that is in Phase I studies; and EC145, a targeted cytotoxic
agent that is in phase I studies. Endocyte has licensed its
vitamin-targeting technology to Bristol-Myers Squibb to target
Bristol-Myers Squibb's proprietary epothilone cancer chemotherapeutic
agents.


Writer: Elizabeth K. Gardner, (765) 494-2081, ekgardner@purdue.edu

Sources:Philip S. Low, (765) 494-5273, plow@purdue.edu

Jun Yang, yangjun@purdue.edu


Related Web sites:

Endocyte: http://www.endocyte.com

Low Research Group: http://www.chem.purdue.edu/low

Proceedings of the National Academy of Sciences posting:
http://www.pnas.org/cgi/doi/10.1073/pnas.0601455103

------------------------------------------------------------


randall...targeting P cells and ringing their bells!

randall

2006-09-10, 4:26 pm

Hi,

P News from around the world.


http://www.globes.co.il/serveen/glo...0131353&fid=942
Can-Fite to develop psoriasis treatment

Adi Ben Israel 10 Sep 06 12:41

Israeli drug development company Can-Fite BioPharma Ltd. (TASE:CFBI)
announced today that it will pursue a new indication in inflammatory
disorders, a field which the company has specialized in over the past
few years. The company said that it will also develop its CF101 drug
for the treatment of psoriasis. This adds to the other indications
currently in different phases of clinical trials, including rheumatoid
arthritis and dry eye syndrome.

The company's laboratory studies in patients with psoriasis have shown
that the target of the drug (Adenosine A3 Receptor) is highly expressed
on the surface of psoriatic cells, and therefore patients with
psoriasis should respond to CF101. Can-Fite is planning to commence
preparations for phase II clinical trials in patients with psoriasis,
after the safety profile of the drug was demonstrated in couple of
phase studies. The psoriasis study protocol is being jointly developed
by the company's clinical team in the US and Prof. Alice Bendix
Gottlieb, a world renowned psoriasis expert and chair of dermatology at
the School of Medicine at Tufts University, Boston.

<sniP>

---------------

7 citations in pubmed for CF101
http://www.ncbi.nlm.nih.gov/entrez/...2&dopt=Abstract

-------------------------------------------------------------------


LOOK at this UVR article.. It says uv's cause the release of iron when
your out in the sunshine.

So, why don't we get cancer and our psoriasis heals instead after
sunbathing?
The P53 articles posted in the last day must have a good clue to this
stuff.

Another couterintuitive psoriasis moment to say the least.

Am I taking iron out of the equation with IP6 and is it a good thing?
http://en.wikipedia.org/wiki/Phytic_acid

http://www.medicalnewstoday.com/med...hp?newsid=51495

New Sunscreen Ingredient To Heal Sunburn And Help Prevent Skin Cancer

People who suffer from sunburn could soon benefit from a new sunscreen
ingredient that actively repairs sunburnt skin and helps prevent the
onset of skin cancer, according to research published in the Journal of
Investigative Dermatology.

Unlike conventional sunscreen lotions which merely act as a filter for
UVA and UVB sunlight, the new ingredient releases an active ingredient
which mops up free iron that is released when the skin burns.

This reduces the inflammation and pain that goes with sunburn - which
is exacerbated by the iron - and also prevents the build up of harmful
sunlight-generated free radicals, which can lead to the development of
skin cancers.

The new ingredient is light-responsive and only becomes active when it
is exposed to UV radiation in sunlight, avoiding any side-effects that
might result from long-term exposure to the active form of the drug.

The researchers are currently testing prototypes of the ingredient in
the laboratory using three dimensional human skin cultures, but expect
to be trialling the ingredient with volunteers in the next two to three
years.

"When skin is exposed to high doses of sunlight, such as when you are
sunbathing, a massive amount of free iron is released in skin cells,"
said Dr Charareh Pourzand from the university of Bath who is working in
collaboration with Dr James Dowden (presently at Nottingham
University).

"This free iron can act as catalysts for the generation of more
harmful free radicals that cause severe cell damage.

"Many forms of cancer are thought to be the result of reactions
between free radicals and DNA, causing mutations that can disrupt the
cell cycle and potentially lead to cancer.

"We wanted to find a way of mopping up sunlight-generated free iron
that produce harmful radicals during exposure to bright sunlight in
order to prevent the unwanted side reactions that can lead to skin
damage and ultimately cancer.

"The best way to do this is using chelators, drugs that bind and
export iron from the body.

"However, long term use of chelators can be toxic for cells as it
starves them of the iron necessary for normal biological processes, for
example the red blood cells that transport oxygen around the body need
iron to work."

Additional hurdles in the research were that many chelators are
ineffective protectors of cells, and many of them are patented and so
cannot be used freely by all researchers. The researchers had to find
chelators which were strong enough to export the excess iron out of
cells, but that would not have an adverse effect on other essential
cellular processes.

After three years of research, the team has designed two commercially
attractive prototypes which are currently in laboratory trials.

The prototypes contain 'caged' iron binding sites which release the
chelators only in response to high doses of UV light, thus avoiding
toxicity to cells.

The new sunscreens containing these components will not only contribute
to preventing and repairing skin damage caused by UV light, but will
also be more effective and will last longer (up to three hours) after
application on the skin than conventional sunscreen lotions.

Skin cancer is one of the most common cancers in the UK and the number
of people who get it is increasing. There are over 70,000 new cases of
skin cancer diagnosed each year in the UK and many cases are not
reported so the real number of cases is probably much higher.

Over 2,000 people die from skin cancer each year in the UK. Cancer
Research UK has recently launched the SunSmart - the UK's national skin
cancer prevention campaign. It is advising people to follow the smart
advice:

- Spend time in the shade between 11am and 3pm
- Make sure you never burn
- Aim to cover up with a t-shirt, hat and sunglasses
- Remember to take extra care with children
- Then use factor 15+ sunscreen

"UVB sunlight is associated with the hottest part of the day, between
10am and 3pm, when the sunlight is brightest," said Dr Pourzand who
works in the university of Bath's Department of Pharmacy &
Pharmacology.

"UVB affects the outer layer of the skin and is the primary agent
responsible for skin blistering and peeling after sunburn."

"UVA sunlight is typically associated with the cooler parts of hot
summer days, before 10am and after 3pm."

"UVA was once thought to have a minor effect on skin damage, but now
it is considered to be a major contributor as it penetrates deeper into
the skin than UVB."

"It is overexposure to UVA that causes the redness and inflammation,
or erythema, associated with sunburn."

"The UVA component of sunlight is dangerous as it acts as an
oxidising agent that forms free radicals which trigger chain reactions
that potentially lead to DNA damage that can convert healthy skin cells
into cancerous ones."

The original research paper, Caged-Iron Chelators a Novel Approach
Towards Protecting Skin Cells Against UV A-Induced Necrotic Cell Death,
is available online from the Journal for Investigative Dermatology.

The research was funded by a Wellcome Trust Showcase Award.

About the BATH UNIVERSITY

Bath is a leading UK university with an international reputation for
quality teaching and research, and with close links with industry and
commerce.

BATH UNIVERSITY
Wessex House
Bath
BA2 7AY
http://www.bath.ac.uk

---------------------------------------------------------------


randall...

randall

2006-09-12, 4:29 pm

Hi,


P News


A pretty flower that keeps your liver alive longer.

http://www.medpagetoday.com/Gastroe...atology/tb/4076

MEXICO CITY, Sept. 11 -- The anti-inflammatory drug colchicine delayed
or prevented liver cancer in patients with hepatitis virus-related
cirrhotic liver disease, according to researchers here.
In a retrospective cohort study of 186 patients with viral cirrhosis,
only 9% of 116 patients treated with colchicine developed
hepatocellular carcinoma over three years' follow-up, compared with 29%
of 70 untreated patients, Oscar Arrieta, M.D., of the Instituto
Nacional de Cancerologia here, and colleagues, reported online in
Cancer.
Among those who developed liver cancer, the onset was delayed for those
given colchicine compared with the non-colchicine patients, said the
investigators in a study that will appear in the Oct. 15 issue of the
journal.

[...]

The protective mechanisms of colchicine could be related to
anti-inflammatory properties and inhibition of mitosis, they said.
Colchicine is an alkaloid agent widely used for the treatment of gout
and other immunologic diseases such a scleroderma, ____psoriasis_____,
and Behcet disease. <sniP>

------------------


http://en.wikipedia.org/wiki/Colchicine

Colchicine is a highly poisonous alkaloid, originally extracted from
plants of the genus Colchicum (Autumn crocus, also known as the "Meadow
saffron"). Originally used to treat rheumatic complaints and especially
gout, it was also prescribed for its cathartic and emetic effects. Its
present use is mainly in the treatment of gout. <sniP>

What does it look like?

http://www.tufts.edu/med/biochemist...colchicine.html

I could eat that. Taking the drug would be safer. lol

Not drinking alcohol or contracting any liver diseases still better.

But, how does one (psoriatic) deal with endogenous endotoxin (LPS)?

Simple. Don't drink and keep your liver and Gi tract healthy.

What's a good food for the Gi tract this time of year?

--------------

How about seedless watermelons? What's the link to colchicine?
Glad you asked,
http://www.mailtribune.com/archive/...swatermelon.htm

========================================

TNF news

For psoriasis,

NF-kappaB (NF-Kb) ----> TNF, IFN etc ----> increased psoriasis

As Dick can attest, enbrel blocks TNF and you clear uP!!


http://www.xagena.it/news/medicinen...b82be271c0.html
TNF level predicts who will develop deadly complication after bone
marrow transplant

Researchers could determine one week after a bone marrow transplant
which patients were likely to develop a serious and deadly
complication, making them candidates for preventive treatment before
any symptoms occur.

Researchers at the university of Michigan Comprehensive Cancer Center
measured the level of a protein called tumor necrosis factor, or TNF,
seven days after patients received a bone marrow transplant.
TNF, a trigger for inflammation, is known to be elevated in people who
develop graft vs. host disease, the most common serious side effect of
a bone marrow transplant from a donor.

Bone marrow transplant is a treatment given to children or adults with
certain types of cancer, such as leukemia or lymphoma, or to people
with some blood or immune disorders. A transplant allows higher doses
of chemotherapy to be used to destroy cancer, because the damaged bone
marrow is replaced by the transplanted healthy marrow. But the
complicated treatment carries a risk of the body rejecting the new bone
marrow, a condition called graft versus host disease, or GVHD.
The transplanted immune cells can attack the patient's skin, liver and
gastrointestinal cells, triggering a massive inflammatory reaction that
can kill the patient.

The study looked at 170 patients, 94 of whom went on to develop graft
versus host disease, a condition in which the transplanted immune
system attacks the patient's normal tissue. Those 94 patients had
elevated levels of the TNF-receptor protein a week after their
transplant, before they showed any symptoms of graft versus host
disease.
Researchers also found patients whose TNF level was elevated at seven
days had a 20-point lower survival rate: 62 percent were alive after a
year, compared to 85 percent of those with a lower TNF.

" This suggests we could target patients to prevent graft versus host
disease based on their post-transplant level of TNF. If we can develop
a test that can reliably predict this complication, we can then look at
treating it before any symptoms develop. This is one small step in a
long road to making transplants safer and more effective," says study
author John Levine, at the U-M Medical School.

Research led by James Ferrara, director of the Blood and Marrow
Transplantation Program at the U-M Comprehensive Cancer Center has
previously linked TNF to graft versus host disease.

" TNF is known to play a role in a variety of inflammatory or
autoimmune diseases, including septic shock, rheumatoid arthritis and
Crohn's disease. Anti-TNF drugs are already FDA-approved and available
on the market. We are currently conducting a clinical trial using one
of these drugs, Etanercept ( Enbrel ), in clinical trials to see if it
can prevent or treat GVHD, " says study author Carrie Kitko, at the U-M
Health System.

About 40 percent to 50 percent of all patients who receive a bone
marrow transplant will develop GVHD, and 30 percent will die from this
complication.

Source: university of Michigan Health System, 2006


--------------------------------------------

Small molecule from hollis-eden to control NF-Kb.

http://www.pharmalive.com/News/inde...2&categoryid=40

Hollis-Eden Pharmaceuticals Presents Data Demonstrating Potential
Therapeutic Benefits of Second-Generation Drug Candidates

SAN DIEGO--(BUSINESS WIRE)--Sep 12, 2006 - Hollis-Eden Pharmaceuticals,
Inc. (NASDAQ:HEPH) announced today that it is presenting preclinical
data at the 12th International Congress on Hormonal Steroids, Hormones
& Cancer being held September 13-16, 2006, in Athens, Greece,
demonstrating indication-specific activity and potential therapeutic
benefits of multiple second-generation compounds derived from the
Company's Hormonal Signaling Technology Platform.

As reported at the meeting, the compounds described include potential
drug candidates that are effective and non-toxic in animal models of
multiple sclerosis, rheumatoid arthritis, diabetes, prostate cancer and
chemotherapy recovery. In addition, the Company reported that it has
made significant progress in defining the mechanisms of action of its
Hormonal Signaling Technology Platform. Specifically, several
second-generation Hollis-Eden compounds regulate ___NF-kappaB___, a
protein that plays a key role in cellular signaling. NF-kappaB
activation leads to the production of inflammatory mediators such as
___TNF-alpha, IL-6, and IFN-gamma___, and controls various other
cellular functions. Thus, NF-kappaB is an important pharmaceutical
target for treatment of inflammatory and metabolic disorders. [and
psoriasis of course]

Hollis-Eden's Hormonal Signaling Technology Platform comprises a
proprietary new class of small molecule compounds that are designed to
restore the biological activity of cellular signaling pathways
disrupted by disease and aging. Through years of research with these
compounds -- metabolic conversions or synthetic analogs of adrenal
steroid hormones -- Hollis-Eden has made significant discoveries
relating to their metabolism, mechanism of action and pharmacologic
profile. <sniP>


------------------------------

Abstracts from pubmed. (last day postings)

This first one was mentioned days ago in a google news story in P News.
http://www.ncbi.nlm.nih.gov/entrez/...l=pubmed_docsum
Mast cell CD30 ligand is upregulated in cutaneous inflammation and
mediates degranulation-independent chemokine secretion.

* Fischer M,
* Harvima IT,
* Carvalho RF,
* Moller C,
* Naukkarinen A,
* Enblad G,
* Nilsson G.

Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology, Radiology, and Clinical Immunology, Uppsala
University, Uppsala, Sweden. Department of Dermatology and Department
of Pathology, Kuopio university Hospital, Kuopio, Finland.

Mast cells are involved in many disorders where the triggering
mechanism that leads to degranulation and/or cytokine secretion has not
been defined. Several chronic inflammatory diseases are associated with
increased mast cell numbers and upregulation of the TNF receptor family
member CD30, but the role of elevated CD30 expression is poorly
understood. Here we report what we believe to be a novel way to
activate mast cells with CD30 that leads to degranulation-independent
secretion of chemokines. CD30 induced a de novo synthesis and secretion
of the chemokines IL-8, macrophage inflammatory protein-1alpha
(MIP-1alpha), and MIP-1beta, a process involving the MAPK/ERK pathway.
Mast cells were found to be the predominant CD30 ligand-positive
(CD30L-positive) cell in the chronic inflammatory skin diseases
psoriasis and atopic dermatitis, and both CD30 and CD30L expression
were upregulated in lesional skin in these conditions. Furthermore, the
number of IL-8-positive mast cells was elevated both in psoriatic and
atopic dermatitis lesional skin as well as in ex vivo CD30-treated
healthy skin organ cultures. In summary, characterization of CD30
activation of mast cells has uncovered an IgE-independent pathway that
is of importance in understanding the entirety of the role of mast
cells in diseases associated with mast cells and CD30 expression. These
diseases include Hodgkin lymphoma, atopic dermatitis, and psoriasis.

PMID: 16964309


http://www.ncbi.nlm.nih.gov/entrez/...l=pubmed_docsum
CXCR2 ligands and G-CSF mediate PKCalpha-induced intraepidermal
inflammation.

* Cataisson C,
* Pearson AJ,
* Tsien MZ,
* Mascia F,
* Gao JL,
* Pastore S,
* Yuspa SH.

Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for
Cancer Research, National Cancer Institute, and Laboratory of Molecular
Immunology, National Institute of Allergy and Infectious Diseases, NIH,
Bethesda, Maryland, USA. Istituto Dermopatico dell'Immacolata, Rome,
Italy.

Transgenic mice overexpressing PKCalpha in the epidermis (K5-PKCalpha
mice) exhibit an inducible severe intraepidermal neutrophilic
inflammation and systemic neutrophilia when PKCalpha is activated by
topical 12-O-tetradecanoylphorbol-13-acetate (TPA). This inducible
model of cutaneous inflammation was used to define mediators of skin
inflammation that may have clinical relevance. Activation of cutaneous
PKCalpha increased the production of the chemotactic factors
cytokine-induced neutrophil chemoattractant (KC) and macrophage
inflammatory protein 2 (MIP-2) in murine plasma. TPA treatment of
cultured K5-PKCalpha keratinocytes also released KC and MIP-2 into
culture supernatants through an NF-kappaB-dependent pathway. MIP-2 and
KC mediated the infiltration of neutrophils into the epidermis, since
this was prevented by ablating CXCR2 in K5-PKCalpha mice or
administering neutralizing antibodies against KC or MIP-2. The
neutrophilia resulted from PKCalpha-mediated upregulation of cutaneous
G-CSF released into the plasma independent of CXCR2. These responses
could be inhibited by topical treatment with a PKCalpha-selective
inhibitor. Inhibiting PKCalpha also reduced the basal and TNF-alpha- or
TPA-induced expression of CXCL8 in cultured psoriatic keratinocytes,
suggesting that PKCalpha activity may contribute to psoriatic
inflammation. Thus, skin can be the source of circulating factors that
have both local and systemic consequences, and these factors, their
receptors, and possibly PKCalpha could be therapeutic targets for
inhibition of cutaneous inflammation.

PMID: 16964312

http://www.ncbi.nlm.nih.gov/entrez/...l=pubmed_docsum
Epidermal sphingolipids: Metabolism, function, and roles in skin
disorders.

* Holleran WM,
* Takagi Y,
* Uchida Y.

Department of Dermatology, School of Medicine, university of California
San Francisco, United States; Department of Pharmaceutical Chemistry,
School of Pharmacy, university of California San Francisco, United
States; Dermatology Service and Research Unit, Department of Veterans
Affairs Medical Center, San Francisco, CA, United States.

Mammalian epidermis produces and delivers large quantities of
glucosylceramide and sphingomyelin precursors to stratum corneum
extracellular domains, where they are hydrolyzed to corresponding
ceramide species. This cycle of lipid precursor formation and
subsequent hydrolysis represents a mechanism that protects the
epidermis against potentially harmful effects of ceramide accumulation
within nucleated cell layers. Prominent skin disorders, such as
psoriasis and atopic dermatitis, have diminished epidermal ceramide
levels, reflecting altered sphingolipid metabolism, that may contribute
to disease severity/progression. Enzymatic processes in the hydrolysis
of glucosylceramide and sphingomyelin, and the roles of sphingolipids
in skin diseases, are the focus of this review.

PMID: 16962101

http://www.ncbi.nlm.nih.gov/entrez/...l=pubmed_docsum
Coexistence of psoriasis and pemphigoid - only a coincidence?

* Lazarczyk M,
* Wozniak K,
* Ishii N,
* Gorkiewicz-Petkov A,
* Hashimoto T,
* Schwarz R,
* Kowalewski C.

Department of Dermatology, Medical university of Warsaw, 02-008 Warsaw,
Poland.

It has previously been reported that pemphigoid coexists with psoriasis
more frequently than it could be predicted on the basis of random
distribution in the general population. In this study we present three
psoriatic patients who developed tense blisters, which most likely were
not provoked by anti-psoriatic treatment. Diagnosis of bullous
pemphigoid in these cases was established by an overlay antigen mapping
technique by laser confocal microscopy, immunoblotting and ELISA. In
the context of these cases and the literature, we also discuss possible
reasons for the coexistence of psoriasis and pemphigoid as well as
selected aspects of diagnosis and therapy of patients simultaneously
suffering from these two diseases.

PMID: 16964414

Here's a good one. What happens after you tan for an hour or so and the
vitamin
D goes to work in the skin, with your DNA.
http://www.ncbi.nlm.nih.gov/entrez/...l=pubmed_docsum
Expression profiling of vitamin D treated primary human keratinocytes.

* Moll PR,
* Sander V,
* Frischauf AM,
* Richter K.

Department of Cell Biology, university of Salzburg, Hellbrunnerstrasse
34, A-5020 Salzburg, Austria.

Vitamin D has attracted much attention by its ability to stop cell
proliferation and induce differentiation, which became of particular
interest for the treatment of cancer and psoriasis. We performed an
expression profile of 12 hours and 24 hours 1alpha,25-dihydroxyvitamin
D(3) (1alpha,25(OH)(2)D(3)) treated primary human keratinocytes, to
determine the changes in gene expression induced by the steroid in
order to improve our understanding of the biological activity of
1alpha,25(OH)(2)D(3). This we expect to be useful for establishing a
test system for vitamin D analogs or might open new therapeutic targets
or uses for the hormone. For the filter array experiments a
non-redundant set of 2135 sequence verified EST clones was used. The
normalized raw data of 2 filters per time point were combined and
subjected to SAM analysis to further increase the statistical
significance. 86 positive and 50 negative genes were identified after
12 h. The numbers went down to 43 positive and 1 negative gene after 24
h of treatment. Fifteen genes are up-regulated over a longer period of
time (12 h and 24 h). Results were verified by real-time PCR and/or
Northern blots. Targets identified are involved in intracellular
signaling, transcription, cell cycle, metabolism, cellular growth,
constitution of the extracellular matrix or the cytoskeleton and
apoptosis, immune responses, and DNA repair, respectively. Expression
profiles showed an initial stop of proliferation and induction of
differentiation, and resumed proliferation after prolonged incubation,
most likely due to degradation of the hormone. J. Cell. Biochem. (c)
2006 Wiley-Liss, Inc.

PMID: 16960875

Don't you hate it when that hormone degrades and there's no sun around
to build up MORE?


randall...


randall....

randall

2006-09-12, 4:29 pm


randall wrote:

<sniP>

> Small molecule from hollis-eden to control NF-Kb.
>
> http://www.pharmalive.com/News/inde...2&categoryid=40
>
> Hollis-Eden Pharmaceuticals Presents Data Demonstrating Potential
> Therapeutic Benefits of Second-Generation Drug Candidates
>

<sniP>

>From Hollis-Eden Today,

http://www.genengnews.com/news/bnitem.aspx?name=5736036

Hollis-Eden Pharmaceuticals Presents Data Demonstrating Potential
Therapeutic Benefits of Second-Generation Drug Candidates
9/12/2006 7:00:00 AM EST

BIOWIRE

[...].

Autoimmunity and Inflammatory Conditions

In its autoimmune program, Hollis-Eden reported that it has developed
orally available compounds -- HE3204 and HE3286 -- that demonstrate
anti-inflammatory activity without immunosuppression.

-- In vitro, HE3204 and HE3286 inhibited NF-kappaB signal transduction
pathways at concentrations lower than that of the widely used
corticosteroid dexamethasone.

-- In a LPS-stimulated mouse model of inflammation, HE3204 decreased
activated NF-kappaB in the spleen and TNF-alpha in the blood.

-- In a preclinical model of multiple sclerosis, a cell-mediated (Th1)
autoimmune disorder, orally administered HE3204 decreased disease and
decreased the production of antigen-specific responses of TNF-alpha,
IL-6 and the Th1 cytokine IFN-gamma.

-- In a preclinical model of rheumatoid arthritis, an antibody-mediated
(Th2) autoimmune disorder, orally administered HE3286 decreased joint
swelling scores and increased the production of antigen-specific
IFN-gamma and TNF-alpha responses in the spleen, indicative of a shift
away from Th2 responses and toward cell-mediated (Th1) immunity.

-- Both compounds have shown good oral bioavailability in primates.

-- Neither compound is immunosuppressive in a number of in vitro and in
vivo immune-stimulation assays.

Metabolic Disorders

Hollis-Eden reported that one of its second-generation compounds,
HE3286, demonstrated benefit when administered orally in animal models
of diabetes.

-- In a model of early, insulin resistant type-II diabetes, HE3286
improved glucose tolerance.

-- In another model of diabetes, HE3286 decreased glucose and
triglycerides.

-- The metabolic effects observed are believed to be driven by the
ability of HE3286 to regulate the NF-kappaB pathway as well as the
metabolic disease-related enzymatic 11betaHSD1 pathway.

Hematology

Hollis-Eden also presented data on HE3210, a potential candidate for
chemotherapy protection.

-- In rhesus monkeys exposed to sublethal radiation, subcutaneously
administered HE3210 produced tri-lineage hematopoiesis, reducing
neutropenia, thrombocytopenia and anemia.

-- In a rhesus monkey model of chemotherapy protection, HE3210 enhanced
regeneration of neutrophils, platelets and red blood cells in animals
receiving carboplatin.

<sniP>

----------------------------------------------------

randall...

JXStern

2006-09-12, 9:32 pm

On 12 Sep 2006 14:06:10 -0700, "randall" <ranhub11@aol.com> wrote:
>In its autoimmune program, Hollis-Eden reported that it has developed
>orally available compounds -- HE3204 and HE3286 -- that demonstrate
>anti-inflammatory activity without immunosuppression.

Well I doubt that.

I don't think it's possible.

The best you can do is tune it.

Now, maybe you can tune it so that instead of being over-inflamed we
are returned to norbal, but officially that would still be
immunosuppression.

J.

ps - "norbal" is a joke from an ancient Mad magazine piece ...

randall

2006-09-13, 4:23 pm


JXStern wrote:
> On 12 Sep 2006 14:06:10 -0700, "randall" <ranhub11@aol.com> wrote:
>
> Well I doubt that.
>
> I don't think it's possible.

Think about it. Small molecules are working on either TNF, IFN etc.

Not the whole immune system, just the skewed Th1 cytokines that
are in over abundance.

>
> The best you can do is tune it.

Agreed

>
> Now, maybe you can tune it so that instead of being over-inflamed we
> are returned to norbal, but officially that would still be
> immunosuppression.

OK fine. Call it norbal or P-B-gone. The small molecules are
the next level for really expensive drugs and will the biologicals
cheaper. Or so we hope.



> J.
>
> ps - "norbal" is a joke from an ancient Mad magazine piece ...

I'll image google it and see.

---------------------------------------------------------------------


And P News



http://www.nutraingredients-usa.com...x-calcification

Calgenex tackles calcification

9/13/2006 - New manufacturer and marketer Calgenex Corporation is
taking the condition-specific approach to supplementation to a very
specific level - tackling soft tissue calcification with a range of
products.

In an effort to set themselves apart from the crowd, more and more
manufacturers and distributors are marketing products to particular
health conditions, as such bypassing the dilemma of relying on consumer
nutritional education and instead directly labeling the health
condition a specific set of compounds supports.

Like many other supplement companies, Calgenex is aiming its soft
tissue calcification support products primarily at the baby boomer
generation - the generation with the most disposable income and also
the age bracket in which the condition manifests itself most
pervasively.

"The company was founded on the premise that calcification is a very
important condition facing Americans today," Calgenex president and
CEO Grant Carlson told NutraIngredients-USA.com. "We have too much
calcium in our bodies that is then forming calcium crystals in our soft
tissues."

The budding Tampa, Florida-based company was founded in February 2006
and has just announced the launch of its Calci Clear product line.
Carlson says the products are to be initially marketed in the US
through both the Internet and infomercials, but he is relying on the
originality of the product health target to bring the products to
retail shelves and other countries.

"It's really a new category," said Carlson of the company's
strategic focus on supplementation for soft tissue calcification.

Calci Clear consists of a three-step program of supplements, which
Calgenex claims cleanses the body of calcium crystals while also
keeping new crystals from forming. The company website describes
ingredients EDTA (ethylenediaminetetraacetic acid), citric acid, sodium
citrate, malic acid, and green algae-derived chlorophyll as the
"sequestering agents" that bind with unwanted calcium crystals and
heavy metals and flush them out of the body.

[maybe my IP6 regime is all that needed?]

Carlson says Calgenex's blend of minerals, vitamins and chemical
compounds is patent-pending and tests are currently underway on its
products in various locations in the US. The Calci Clear ingredients
include: green algae chlorophyll, chlorella, as well as antioxidants
like alpha lipoic acid, pycnogenol pine bark extract, grape seed
extract and coenzyme Q10.

Under normal mineral conditions in the body, calcification is limited
to bones and teeth, but when soft tissue calcification occurs, tissue
hardens into bone-like material. While calcium is an essential nutrient
for the body, when other mineral deficiencies occur in the body -
according to Calgenex - an imbalance can result in calcium flowing into
the cells, which become more hyperactive and excitable.

Soft tissue calcification is associated with numerous chronic health
conditions such as atherosclerosis, arthritis, kidney stones,
prostatitis, _____psoriasis____, cataracts, and many more. Also known
as ectopic calification, the condition can be associated with cell
death and damage vessels, tissues, and organs such as the heart,
kidneys, brain, skin, joints, breast, eye, liver, prostate, and
ovaries.

Calgenex sought out its niche in the condition it says plays a role in
many serious diseases.

"We recognized that soft tissue calcification and inflammation were
at the heart of many health conditions affecting millions of Americans
and that they could be addressed by certain ingredients found in
nature," said Carlson.

A look at arthritis statistics gives a glimpse at the possible
occurrence of soft tissue calcification in the US. Soft tissue
calcification can result from arthritis - specifically from crystal
deposition diseases that fall under the category of inflammatory
arthritis. And by 2030, an estimated 67 million of Americans aged 18
years or older will have doctor-diagnosed arthritis, according to data
from the National Center for Health Statistics.

------------------

This brings back the nanobac questions of yore!
Are they still out there?

YeP!
http://www.pharmalive.com/News/inde...egoryid=36%2C61


And the pubmed for keywords: psoria* + ion + calcium
http://www.ncbi.nlm.nih.gov/entrez/...ia*+calcium+ion
Or
http://www.ncbi.nlm.nih.gov/entrez/...%20psoria*+ca2+
Most definitely in the pathways. But are nanobac bugs responsible? I
doubt it. Will believe it if I see it duplicated in peer review
studies.

Look at this,
http://www.thestate.com/mld/thestat...th/15493511.htm

[...]

"Anger is a self-defense mechanism," says Boland. "If we are
trapped and cannot escape, anger helps us fight our way to safety -
the fight part of 'fight or flight.' "

And, as Boland explains, because our bodies undergo such a physical
reaction when we're experiencing anger - increased heart rate,
adrenaline flowing, blood vessels constricting - showing anger during
anything other than a life-or-death struggle can actually take a toll
on our health.

"It's really easy to oversimplify, but the idea is, if you're not
physically in danger or don't have to defend yourself, you'll
handle situations better if you're calm," says Boland.

In fact, researchers at the university of Utah recently found that
couples engaged in "hostile, dominant or controlling" behaviors had
higher levels of _____calcification____, or hardening of the arteries,
after fighting than those who had healthier exchanges. <sniP>

-------------------------

Just getting angry will calcify you. Seems to be more prevalent then
nannobac bugs and still only 2% of the population gets P!


randall.... my 2% and or scents..odd huh? I am about 2% now!

randall

2006-09-14, 2:23 am

Hi,


Breaking P News

In regards to TNF.

http://www.eurekalert.org/pub_relea...c-psf090706.php

Public release date: 12-Sep-2006

Contact: Aline McKenzie

UT Southwestern Medical Center
Pre-clinical study finds Parkinson's cell death blocked by stopping
inflammatory factor
Blocking one of the body's natural inflammatory factors gives
substantial protection against cell death in the brain associated with
Parkinson?s disease, researchers led by Dr. Mal? Tansey, assistant
professor of...
Click here for more information.

DALLAS ? Sept. 12, 2006 ? Blocking one of the body's natural
inflammatory factors gives substantial protection against cell death in
the brain associated with Parkinson's disease, researchers at UT
Southwestern Medical Center have found in a study on rats.

By using a drug against an inflammatory molecule called tumor necrosis
factor or TNF, the researchers saw a 50 percent drop in dopamine neuron
death in the brains of rats injected with compounds that cause
Parkinson's-like cell death.

"Our findings suggest that TNF-dependent inflammation may be part of
the progressive features of Parkinson's disease, and this gives us an
opportunity with anti-TNF therapy to slow down or prevent the
progression of the disease," said Dr. Mal? Tansey, assistant
professor of physiology at UT Southwestern and senior author of the
study. "Our prediction is that independent of the environmental toxin
or trigger that induces its production in the midbrain, TNF is likely
to be a common mediator of dopamine neuron death."

The research will appear online and in the Sept. 13 issue of the
Journal of Neuroscience.

Tumor necrosis factor is necessary for a functioning immune system. Its
effects include the local inflammation and redness around wounds, and
the painful swelling around joints in rheumatoid arthritis. TNF also
activates other cells ? including cells in the brain called microglia
? that eat bacteria and other pathogens.

While the results point in a direction for treating neurodegenerative
diseases with anti-inflammatories, a few problems will need to be
addressed before anti-TNF therapies could come into widespread use to
fight neurodegeneration, Dr. Tansey said. For instance, commercially
available anti-TNF drugs as well as the new drug used in this study are
too large to independently cross from the bloodstream into brain
tissue.

Parkinson's disease affects 5 percent of people over 65, and is the
second most common neurodegenerative disease after Alzheimer's.
Parkinson's disease comes about because of the death of a certain class
of nerve cells in an area of the brain called the substantia nigra. By
the time serious symptoms appear, more than 80 percent of the
dopamine-producing nerve cells are already dead, and the damage is
irreversible.

In addition to its beneficial role, TNF has been a suspected player in
Parkinson's because elevated levels of it are found in post-mortem
brains and cerebrospinal fluid of people with the disease. A previous
study by other researchers found that non-steroidal anti-inflammatory
drugs that block production of TNF and related molecules can reduce the
risk of developing Parkinson's by 46 percent.

In the current study, UT Southwestern researchers injected two
different substances into the rats' brains to cause cell death in the
substantia nigra ? low-dose infusion of LPS, a toxin from bacteria
often used to mimic chronic inflammation of the central nervous system,
and 6-hydroxydopamine, which kills cells by creating an overwhelming
amount of reactive oxygen and nitrogen molecules. Cell death was
measured by counting neurons in stained brain slices.

When an experimental TNF inhibitor called XENP345, designed
specifically to block soluble TNF, was also introduced into the brain,
dopamine neuron death was reduced by about half.

The same effect was found on cultured dopamine neurons exposed to
either toxin.

The researchers are now looking into why TNF inhibition did not fully
protect against cell death. For example, the drug may not have been
able to fully diffuse throughout the tissue, it might take longer to
work than the weeks allowed in the experiment, or dopamine neuron loss
might also involve processes independent of TNF.

"If an intervention could still reduce the extent or rate of cell death
by 50 percent, it could make a huge difference in the life of a
Parkinson's disease patient," Dr. Tansey said.

###

Other UT Southwestern researchers involved in the study were graduate
students Melissa McCoy and Terina Martinez; Kelly Ruhn, research
assistant in physiology; Christine Smith, research assistant at the
Mobility Foundation Center; Dr. Barry Botterman, associate professor of
cell biology; and Dr. Keith Tansey, assistant professor of neurology. A
researcher at Xencor, Inc., which manufactures the experimental TNF
inhibitory compound XENP345, also contributed.

The work was supported by the Michael J. Fox Foundation for Parkinson's
Research.

This news release is available on our World Wide Web home page at
http://www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via e-mail,
subscribe at www.utsouthwestern.edu/receivenews

Dr. Malu Tansey -
http://www.utsouthwestern.edu/findf...6,54903,00.html



---------------------------



randall.. I wish I knew how much TNF i have from second to second.

randall

2006-09-14, 9:24 pm


JXStern wrote:
> On 13 Sep 2006 19:34:40 -0700, "randall" <ranhub11@aol.com> wrote:
>
> ...
> ...
>
> Kewl! So, how 'bout turmeric, isn't it supposed to be anti-TNF?

106 hits, hope to shout,
http://www.ncbi.nlm.nih.gov/entrez/...%20curcumin+tnf

>
> Is incidence of Parkinson's in India, like zero?

Why don't we go to pubmed and find out?

OK, I will.
http://www.ncbi.nlm.nih.gov/entrez/...rm=%20parkinson's+curcumin

&
http://www.ncbi.nlm.nih.gov/entrez/...rm=%20parkinson's+india
&
http://www.ncbi.nlm.nih.gov/entrez/...urcumin+psoria*

That first one is good enough for me.

Yet, empirically i haven't been able to really ascribe more then a few
percent of
effectiveness to my own usage.

So, i'm led to the conclusion of dr. Heng for topical usage.

But then like frosty what's making me itch when I do use it topically?

So, many questions and not enough time.

So, make time and push the rest of life in to also ran.

-------------------------------------

How about a cancer drug uPstream of cancer and autoimunity?

This next one could be a great low dose candidate.

Perfect for cocktail time?


http://www.forbes.com/forbeslife/he...cout534948.html
Cancer Drug Gleevec May Ease Rheumatoid Arthritis
09.14.06, 12:00 AM ET

THURSDAY, Sept. 14 (HealthDay News) -- The cancer "wonder" drug
Gleevec, used to beat back leukemia and certain types of stomach
tumors, also shows promise against autoimmune diseases such as
rheumatoid arthritis.

"The data are very impressive, as impressive as anything I've ever
studied," said study researcher and Stanford university rheumatologist
Dr. William H. Robinson.

His team's findings were published online Sept. 14 in advance of their
publication in the October print issue of the Journal of Clinical
Investigation.

Robinson's group was screening drugs that might possibly help the
estimated 50 percent of rheumatoid arthritis patients who do not
adequately respond to current therapies.

Intrigued by case reports showing that rheumatoid arthritis symptoms
improved in patients who received Gleevec (imatinib) as part of their
cancer treatment, the researchers decided to test the drug in a mouse
model of rheumatoid arthritis. These mice developed a disease similar
to rheumatoid arthritis called collagen-induced arthritis.

Gleevec almost completely prevented the development of collagen-induced
arthritis in healthy mice, Robinson's team reported. Compared to
results in untreated mice, the drug also stopped disease progression
and significantly reduced levels of bone destruction, inflammation, and
tumor-like growth in and around the linings of joints.

The researchers also tested Gleevec on cells taken from the joints of
humans with rheumatoid arthritis. They found that the drug shut down
the cells' production of tumor necrosis factor-alpha (TNFa), a
messenger molecule that drives rheumatoid arthritis-associated
inflammation.

Gleevec also halted the proliferation of fibroblasts, the cells that
cause tumor-like growth in joint linings.

"Gleevec inhibits several types of cells that are critical in
rheumatoid arthritis," Robinson said. "But these cells are also
critical in other diseases such as scleroderma,
________psoriasis_______ and inflammatory bowel disease. Our results
suggest a need for clinical trials of Gleevec in several human
autoimmune diseases to see if it provides a benefit."
<sniP>

-----------------------------------------


randall...so many herbs, so little time. So we cocktail to clearness.

randall

2006-09-24, 4:25 pm

Hi,

P News ..

Your own day coming next month.

You have it every day and now one day set aside for it?

What's up with that?


http://www.medicalnewstoday.com/med...hp?newsid=52454

Aims And Purposes Of World Psoriasis Day, 29th October

World Psoriasis Day is an evolving project with more and more
individuals, experts and patient associations from around the world
getting involved over time. The aims for WPD were defined by the
Steering Committee as follows:

1. Raise awareness about psoriasis: World Psoriasis Day communication
and activities should for example explain that psoriasis is a non
contagious skin condition that can affect anybody and that people with
psoriasis are really no different inside from anyone else. The World
Psoriasis Day project should also aim to dispel myths about the
condition.

2. Encourage healthcare decision makers to give psoriasis suffers
better access to the most appropriate therapies for their condition:
World Psoriasis Day should aim to encourage healthcare decision makers
for example governments, physicians, carers and all those responsible
for psoriasis care/ medicines to allow psoriasis sufferers access to
all the most appropriate therapies. For too long psoriasis has not been
seen as a priority with patients not always getting access to the most
appropriate therapies for their condition.

3. Deliver relevant information and knowledge to interested parties:
World Psoriasis Day should aim to provide information and knowledge to
those who are affected by psoriasis/ psoriatic arthritis as well as the
general public, in order that people can be better informed about the
condition, develop a better understanding, enabling them to be more
confident to speak about it.

4. Provide a patient voice platform: World Psoriasis Day should provide
a platform from which the 'patient voice' can be heard and from which
people with psoriasis can be encouraged to speak out about their needs
and wants.


www.worldpsoriasisday.com

--------------------------------------

We have our P day. Lets get the facts straight?

http://www.medicalnewstoday.com/med...hp?newsid=52456

Facts About Psoriasis

Psoriasis is a debilitating condition that requires continuous
treatment. It is a dry, scaly skin condition in which cells are
produced too quickly. 125 million people worldwide - up to 3% of the
population have psoriasis.

-- 23% of people - that's 28 million - with psoriasis go on to develop
psoriatic arthritis. Quality of life (QoL) research shows that people
with psoriasis have almost the same reduction in QoL as people with
diseases such as cancer, diabetes or depression. Psoriasis can even
lead some patients to consider suicide as the only alternative they
have.

-- It is not contagious.

-- No one treatment works for everyone.

-- Psoriatic arthritis is a specific type of arthritis, which is
usually associated with psoriasis. It causes pain and inflammation in
and around the joints.

-- Many people with psoriasis/psoriatic arthritis avoid social
activities including swimming for fear of the reaction of those around
them.

-- Poor diagnosis and treatment means that many people with psoriasis
and psoriatic arthritis suffer in silence.

-- Recently, new biological therapies have been introduced giving new
hope to people with psoriasis

-----------------------------------------

Here's an odd fact. The city of beijing has a bad case of *psoriasis*!

Real SCARS already.

http://www.chinadaily.com.cn/china/...tent_695515.htm

[...]
The proposed fines are part of the city's latest efforts to rid itself
of the "psoriasis on the urban landscape": the small flyers pasted on
electric poles, public phone booths, bus stops, pavements and even
police cars. <sniP>

[china seems to be the one place with an ePidemic]


------------------------------

Another P factoid you should know.

A psorisis drug with some BAD facts.

http://www.fortwayne.com/mld/journa...ng/15595630.htm

Debate again shadows Accutane

Virtually no one opposes the goal of the mandatory new federal program
governing the use of Accutane: to prevent pregnant women from taking
the potent acne drug, approved in 1982, because it causes serious birth
defects.

That is where the consensus about the unusually restrictive
six-month-old program known as iPledge ends. The program requires
registration of all parties: wholesalers who sell it, pharmacists who
dispense it, doctors who prescribe it and, above all, patients who take
the drug.

Public health officials say such strict regulation is necessary because
years of progressively stronger voluntary programs failed to prevent
pregnancy in users of the medicine, a treatment of last resort for
severe scarring acne. Most of the estimated 200,000 Americans who take
the drug generically known as isotretinoin each year are younger than
30; half are female.

Others - including Rep. Bart Stupak, D-Mich., whose teenage son shot
himself to death in 2000 while taking Accutane and who has addressed a
congressional hearing on the drug's safety - have long advocated
tight controls, or a ban, on the drug because of its possible link to
psychiatric problems. <sniP>

[randall note: we've seen suicidal problems with psoriatics taking this
drug in our
newsgroup.]

----------------------------

NOW all the facts about P. Or different P's anyway.

--------------------------------------
http://www.medicalnewstoday.com/med...hp?newsid=52457
What Is Psoriasis?

Psoriasis is a dry, scaly skin condition in which cells are produced
too quickly. Normally skin cells take about 21-28 days to replace
themselves, in psoriasis they take around 2-6 days. It affects
approximately 3% of people globally. It usually develops between the
ages of 11 and 45. It is not contagious. Psoriasis is unpredictable.
Some people with the condition suffer from social exclusion and
discrimination

What are the symptoms?

-- Normally there is a constant shedding of dead cells. However, due to
the acceleration of the replacement process, both dead and live cells
accumulate on the skin surface. Often this causes red, flaky, crusty
patches covered with silvery scales, which are shed easily.

-- It can occur on any part of the body although it is most commonly
found on the elbows, knees, lower back and the scalp. It can also cause
intense itching and burning.

Who is at risk?

-- Psoriasis affects approximately 3% of people globally. It can start
at any age, but most often develops between the ages of 11 and 45,
often at puberty.

-- The condition is not contagious and most people have only small
patches of their body affected.

-- There is a genetic link and it tends to run in families. About 30%
of people with one first degree relative with psoriasis develop the
condition.

-- This genetic tendency appears to need to be triggered by infection;
certain medicines, including ibuprofen and lithium; psychological
factors, including stress; or skin trauma.

-- There is no way of predicting who will develop psoriasis. 50-60% of
people who first experience it do not know of anyone else in their
family who has had it.

Plaque psoriasis

-- About 80% of those who have psoriasis have this form. It is
characterized by raised, inflamed, red lesions covered by a silvery
white scale. It is typically found on the elbows, knees, scalp and
lower back, although it can occur on any area of the skin.

Inverse psoriasis

-- Inverse psoriasis is found in the armpits, groin, under the breasts,
and in other skin folds around the genitals and the buttocks.

-- This type of psoriasis first shows up as lesions that are very red
and usually lack the scale associated with plaque psoriasis. It may
appear smooth and shiny.

-- Inverse psoriasis is particularly subject to irritation from rubbing
and sweating because of its location in skin folds and tender areas. It
is more common and troublesome in overweight people and people with
deep skin folds.

Erythrodermic psoriasis

-- Erythrodermic psoriasis is a particularly inflammatory form of
psoriasis that often affects most of the body surface. It generally
appears on people who have unstable plaque psoriasis, where lesions are
not clearly defined. It is characterized by periodic, widespread, fiery
redness of the skin.

-- The erythema (reddening) and exfoliation (shedding) of the skin are
often accompanied by severe itching and pain. Erythrodermic psoriasis
"throws off" the body chemistry, causing protein and fluid loss that
can lead to severe illness.

-- Edema (swelling from fluid retention), especially around the ankles,
may also develop along with infection.

-- The body's temperature regulation is often disrupted, producing
shivering episodes. Infection, pneumonia and congestive heart failure
brought on by erythrodermic psoriasis can be life threatening. People
with severe cases of this condition are often hospitalized.

Guttate psoriasis

-- This often starts in childhood or young adulthood and resembles
small, red, individual spots on the skin that are not normally as thick
or as crusty as lesions of plaque psoriasis.

-- A variety of conditions have been known to bring on an attack of
guttate psoriasis, including upper respiratory infections,
streptoccocal infections, tonsillitis, stress, injury to the skin and
the administration of certain drugs (including antimalarials, lithium
and beta-blockers).

-- This form of psoriasis may resolve on its own, occasionally leaving
a person free of further outbreaks, or it may clear for a time only to
reappear later as patches of plaque psoriasis.

Pustular psoriasis

-- Primarily seen in adults, pustular psoriasis is characterized by
white pustules (blisters of noninfectious pus) surrounded by red skin.
It is not an infection, nor is it contagious.

-- This relatively unusual form of psoriasis affects fewer than 5% of
all people with psoriasis.

-- It may be localized to certain areas of the body, for example, the
hands and feet. Pustular psoriasis also can be generalized, covering
most of the body. It tends to go in a cycle: reddening of the skin
followed by formation of pustules and scaling.

-------------------------------

Skin tanning news.

http://www.thecrimson.com/article.aspx?ref=514406


The coming of winter doesn't mean the end of tanning season-at
least, not if you're a mouse.

The Harvard-affiliated Dana-Farber Cancer Institute has provided
red-haired rodents with a way to brown. And the discovery could have
major implications for the prevention of melanoma-a disease that is
estimated to strike one in 75 Americans at some point in their
lifetime.

In a study published yesterday by the journal Nature, David E. Fisher,
director of the Melanoma Program at Dana-Farber and a professor in
pediatrics at Children's Hospital Boston, has found that induced tans
protect at-risk mice-and, potentially, humans-from skin cancer.

For the study, Fisher generated red-haired mice, which, like
fair-skinned humans, were unable to tan. After applying a topical
cream, which triggered the tanning machinery in the mice skin cells,
Fisher was able to give mice a tan without exposing them to harmful UV
light.

"We learned the normal pathway in easily tanning individuals and
identified the block that occurs in red-heads and fair-skinned
individuals. With that information we have identified a drug which
rescues the pathway in mice," Fisher said in a phone interview.

The study also showed that tans acquired through this process protect
against the deadliest form of skin cancer, melanoma.

"For humans, sunburn can already be prevented by sunscreen," Fisher
said. But, he added, "it really is not clear if traditional sunscreen
can prevent melanoma."

Although the study has made huge strides, it still has a long way to
go.

"We would still need to figure out an effective way to apply our
findings to humans," said former Harvard Medical School instructor
John A. D'Orazio, who assisted Fisher's study for the past
three-and-a-half years. "We're also looking at safety issues and
possible side-effects," added D'Orazio, now a pediatrics professor
at the