PSOR ANAL OLOGY or MORE CRAP taxing your SYSTEM
randall
Only a few hours old and HOT off the press.
Actually longer then that. But i've been side lined so many times
today i don't know if i'm coming or going.
I do know it's....
A NEW PSOR DRUG...and it
Works the guanylhydrozone pathways. Which is...
CRAP.
Once again---> psor folks are full of crap.
Don't you just love it?
Obama and the democraps with glib craPPish lies of Global warming
(AGW) are
so full of themselves I can smell them thousand of miles away.
Yuck OH... & they told the world that stench was BUSh. LOL
Didn't Obama become a BUSH somewhere over the RAINBOW? And the bloom
is off the
SOROS rose in socialist paradigms?
By any other name he'd still be insane.
If dems were smart, instead of playing the tax crack addict come line
CARD (or CRAP table being the anal ology here) they'd distance
themselves from this AGW issue. LOL
But, but, butt on the WHOLE i'd still KNOW, even,
If i was on the SUN, i'd know they lie. LOL
So go OH Obama-NATION on your nobel quest to copenhagen for which you
dID nothing.
Then caP and TRADE us to death with incessant taxes to put the stake
in the heart of
crapitalism LOL
http://www.ogj.com/index/blogs/health-safety-environment/blogs/OGJ/health-safety-environment-blog/post987_8699911304423452277.html
http://en.wikipedia.org/wiki/Emissions_trading
Yet psor and democrat lemmings don't want to know the TRUTH.
Why the one in the wilderness cries?
Chop off his head and give it to your daughter?
John the baptist or obama the crapitalist can relate?
It's universal and destroys your world view:
Why?
Just the nature of pending change i guess.
http://www.chinesenames.org/chinese-symbols/change.htm
or more in western tradition without getting all yin yang on our
heads.
http://en.wikipedia.org/wiki/World_view#Worldview_and_linguistics
And besides Weltanschauung and Weltschmerz you want what you simply
want, regardless of
ontology and beliefs.
Small ___rodents___ want free gov money from their fellow citiZENs.
And small prezidents offer it up to build ever bigger big PIG gov.
http://en.wikipedia.org/wiki/Lemming
Their so cute. How could i ascribe perfidiousness to them?
I won't. <G>
To those elite socialist who have smaller members and envy of
their capitalist couter parts i will ascribe perfidity and
stuPidly. ;~?
http://en.wikipedia.org/wiki/Socialism
So here's to those huMANs on their POWER TRiPs..
ARE they both foul of crap? Like one says about the udder or your
mudder?
How about another drug to get the crap out of YOU?
Since we're not about to get the craP out of the oval office i'll give
it
a try.
WhooPs, DO i mean, all we get is crap from this oval office?
Now find out about the CRAP in you.
Ubiquitious CRAP (see last few googles for this term)***
http://www.prnewswire.com/news-releases/cytokine-pharmasciences-completes-phase-i-study-of-oral-anti-inflammatory-agent-cpsi-2364-78135497.html
Cytokine PharmaSciences Completes Phase I Study of Oral Anti-
Inflammatory Agent, CPSI-2364
Phase II Study in Crohn's disease will be initiated in early 2010
KING OF PRUSSIA, Pa., Nov. 30 /PRNewswire/ -- Cytokine PharmaSciences,
Inc. today announced the completion of a Phase I study of CPSI-2364,
its orally active, small-molecule inhibitor of the production of TNF-
alpha and other pro-inflammatory cytokines. Results of the safety and
tolerability dose escalation study in healthy volunteers confirm the
safety of this compound in initial clinical testing.
All 30 enrolled subjects completed the study, including those
receiving the highest dose of CPSI-2364 (270 mg), approximately 30
times the dose that animal models predict will be effective. The drug
was well-tolerated with a low incidence of mostly mild adverse
events.
"We have now demonstrated that CPSI-2364, a more soluble salt form of
semapimod, is safe in humans at doses well above those required for
efficacy," said Dr. Thais Sielecki, Vice President of Preclinical
Development at Cytokine PharmaSciences. "We have also established a
target dose range that we believe optimizes the therapeutic index for
CPSI-2364 for use in our next stage of clinical testing."
A Phase II study in patients with Crohn's disease is planned for early
2010.
About CPSI-2364
CPSI-2364 is a chemically-modified form of the synthetic
guanylhydrozone, semapimod. Semapimod has been shown to inhibit the
signal transduction pathways that lead to the production of nitric
oxide and important pro-inflammatory cytokines, including TNF-alpha,
IL-1, IL-6, and IL-8. Semapimod has demonstrated activity in multiple
animal models of inflammation and autoimmune disease, proof-of-concept
studies that led to human clinical trials. An intravenous formulation
of semapimod was shown to have significant anti-inflammatory activity
in Phase II clinical trials in Crohn's disease, psoriasis and ERCP-
induced pancreatitis. However, that formulation caused dose-limiting
local reactions, such as phlebitis. To overcome this problem, the
Company developed CPSI-2364, a more soluble salt of semapimod that
makes oral dosing possible. Animal models have confirmed the oral
activity of CPSI-2364.
<sniP>
-----
This new psoriasis and crohn's product is designed to slow NO (nitric
oxide) and slow TNF.
http://en.wikipedia.org/wiki/Semapimod
Semapimod (INN), formerly known as CNI-1493, is an investigational new
drug which has anti-inflammatory[1], anti-cytokine[2], immunomodulatory
[3], antiviral[4] and antimalarial[5] properties.
Mechanism of action
Semapimod was first developed to inhibit nitric oxide synthesis by
inflammatory macrophages, via inhibition of the uptake of arginine
which macrophages require for nitric oxide synthesis.[1] Subsequently
it was found that suppression of nitric oxide synthesis occurred even
at semapimod concentrations 10-fold less than required for inhibition
of arginine uptake, suggesting that this molecule was a more general
inhibitor of inflammatory responses.[2] Further work revealed that
semapimod suppressed the translation efficiency of tumor necrosis
factor production.[6] Specifically, semapimod was found to be an
inhibitor of p38 MAP kinase activation.[7] Surprisingly, however, the
primary mode of action in vivo is now thought to be via stimulation of
the vagus nerve, thereby down-regulating inflammatory pathways via the
recently discovered cholinergic anti-inflammatory pathway.[8][9]
Pharmacology and clinical trials
In a preclinical study in rats, semapimod was found to suppress
cytokine-storm induction by the anticancer cytokine interleukin-2
(IL-2) without decreasing its anticancer properties, allow larger
doses of IL-2 to be administered.[10] A subsequent phase I trial in
humans failed to show an increase in the tolerated dose of IL-2,
although indications of pharmacological activity as an inhibitor of
tumor necrosis factor production were observed.[11]
In a preliminary clinical trial of semapimod in patients with moderate
to severe Crohn's disease, positive clinical changes were observed,
including endoscopic improvement, positive responses in some patients
not responding to infliximab, healing of fistulae, and indications for
tapering of steroids; no significant adverse effects were observed.
[12]
In a small clinical trial against post-ERCP pancreatitis, significant
suppression was not observed, although investigators observed a
significant reduction of the incidence of hyperamylasemia and the
levels of post-ERCP amylase.[13]
In the clinical trials above, semapimod tetrahydrochloride was
administered by intravenous injection. This route has drawbacks such
as dose-limiting phlebitis.[2] Recently Cytokine PharmaSciences has
announced the development of novel salt forms of semapimod which are
said to be orally absorbable; a phase I clinical trial of one of these
salt forms, CPSI-2364, has been completed, and a phase II trial is
planned for 2010.[3][4]
Chemistry
Semapimod is synthesized by reacting 3,5-diacetylaniline[14] with
sebacoyl chloride in the presence of pyridine, followed by reaction of
the resulting tetraketone with aminoguanidine hydrochloride.[1]
<sniP>
What is guanylhydrozone exactly?
OK, if you came this far, we can get down and dirty.
THE ultimate crap in you and i....but i have a lot less now. LOL
Let's go back to the stone age. 1984 with barney rubble, fred
flintstone and George Orwell:
www.ncbi.nlm.nih.gov/pubmed/6433883
___1984___ Jul 15;221(2):483-8.
Glyoxal bis(guanylhydrazone) as an inhibitor of polyamine biosynthesis
in tumour cells.
Seppänen P, Fagerström R, Alhonen-Hongisto L, Elo H, Lumme P, Jänne J.
Glyoxal bis(guanylhydrazone), the parent compound of methylglyoxal bis
(guanylhydrazone), was synthesized and tested for its ability to
inhibit the biosynthesis of polyamines. It was found to be a powerful
competitive inhibitor of adenosylmethionine decarboxylase (EC
4.1.1.50), yet the lack of the methyl group at the glyoxal portion
increased the apparent Ki value for the enzyme by about 30-fold in
comparison with methylglyoxal bis(guanylhydrazone). Glyoxal bis
(guanylhydrazone) inhibited diamine oxidase (EC 1.4.3.6) activity as
effectively as did methylglyoxal bis(guanylhydrazone). The cellular
accumulation curves of glyoxal bis(guanylhydrazone) in L1210 cells
were practically superimposable with those of methylglyoxal bis
(guanylhydrazone), and the uptake of both compounds was distinctly
stimulated by a prior treatment with 2-difluoromethylornithine. The
drug decreased the concentration of spermidine in a dose-dependent
manner and, in contrast with methylglyoxal bis(guanylhydrazone),
without a concomitant accumulation of putrescine. The fact that
putrescine concentrations were decreased in cells exposed to glyoxal
bis(guanylhydrazone) was, at least in part, attributable to an
inhibition of ornithine decarboxylase (EC 4.1.1.17) activity in cells
treated with the compound. Under these experimental conditions
equivalent concentrations of methylglyoxal bis(guanylhydrazone) [1,1'-
[(methylethanediylidine)dinitrilo]diguanidine] elicited large
increases in the enzyme activity. When combined with
difluoromethylornithine, glyoxal bis(guanylhydrazone) potentiated the
growth-inhibitory effect of that drug. Taking into consideration the
proven anti-leukaemic activity of glyoxal bis(guanylhydrazone), its
effectiveness to inhibit spermidine biosynthesis (without raising the
concentration of putrescine) as well as its suitability for combined
use with inhibitors of ornithine decarboxylase, this drug is
apparently worthy of further testing in tumour-bearing animals,
especially in combination with difluoromethylornithine or related
inhibitors of ornithine decarboxylase.
PMID: 6433883 [PubMed - indexed for MEDLINE]
And the full (craPPy) story on this abstract:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1144063/
Dr Juhani Jänne, Department of Biochemistry, University of Helsinki
Has hundreds of polyamine abstracts.
161 returns for him and polyamine in pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=%22Janne+J%22%5BAuthor%5D+AND+polyamine&log$=activity
Three of those 161 returns has keyword (for us psoriatics anyway)
psoriasis in them.
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=%22Janne+J%22%5BAuthor%5D+AND+polyamine+AND+psoria*&log$=activity
Isn't this funny. Jänne has an abstract from 1984 for a psoriasis drug
that is
now available in an ORAL form intead of an injection? LOL
www.ncbi.nlm.nih.gov/pubmed/6207853
1984 Oct;111(4):403-11.
Effect of polyamine antimetabolites on cultured human keratinocytes
from normal and uninvolved psoriatic skin.
Käpyaho K, Kariniemi AL, Virtanen I, Jänne J.
We describe the effect of two polyamine antimetabolites on polyamine
and macromolecule synthesis of cultured human keratinocytes obtained
by suction blisters from normal skin and the uninvolved skin of
psoriatic patients. The concentrations of spermidine and spermine
steadily increased during the culture of normal keratinocytes in
vitro, whereas the putrescine concentration showed only a transient
rise at the beginning of the active growth phase. Treatment with
difluoromethylornithine decreased the concentrations of putrescine and
spermidine in both normal and uninvolved psoriatic keratinocytes, but
had no effect on either DNA or protein synthesis. Methylglyoxal bis
(guanylhydrazone) marginally decreased the levels of spermidine and
spermine and significantly inhibited the DNA and protein synthetic
activities. Pretreatment of uninvolved psoriatic keratinocytes with
difluoromethylornithine enhanced the accumulation of methylglyoxal bis
(guanylhydrazone), resulting in a profound inhibition of cellular
macromolecule synthesis. This synergistic effect was not seen in
normal keratinocytes. Thus, although no statistically significant
difference was observed between the cells derived from normal and
uninvolved psoriatic epidermis, the psoriatic keratinocytes appeared
to be more sensitive to the action of polyamine antimetabolites. The
inhibition of DNA and protein synthesis by methylglyoxal bis
(guanylhydrazone) was prevented by concomitant treatment with
spermidine.
PMID: 6207853
--------------
What is it with putrescine, polyamines and spermidine?
I call them the crap brothers. I can only wonder why Jänne spent
most of his life studying them. <W> <g>
Oh Brother where for fart thou?
Oh crap, that is a GOOD one:
http://www.youtube.com/watch?v=OF5OtSO3j6I
THE SOGGY BOTTOM BOYS - OH BROTHER WHERE ART THOU-
H'mmm love the sirens in the river scene. Nice and simPle distraction
and communicates---->
http://www.greek-gods.info/ancient-greek-gods/sirens/
Or is the booze more of a Bacchus god of WINE thing.
http://www.crystalinks.com/bacchus.html
How about both?
But i shouldn't discount
http://en.wikipedia.org/wiki/Dionysus
http://en.wikipedia.org/wiki/Dionysus#Modern_views
And Eleusinian mystery or secrets
http://en.wikipedia.org/wiki/Eleusinian_mysteries#Greater_Mysteries
[...]
Upon reaching Eleusis, there was a day of fasting in commemoration of
Demeter's fasting while searching for Persephone. The fast was broken
while drinking a special drink of barley and pennyroyal, called
kykeon.
<sniP>
With ergot in this wine you got the LSD kicker i suPPose
http://en.wikipedia.org/wiki/Kykeon
Certainly the Oh Brother writer didn't expect someone to make that
connection. LOL
But a lover of literature might impute more under the sun then is
warranted. <g>
http://en.wikipedia.org/wiki/Eleusinian_Mysteries#Entheogenic_theories
Certainly the AGW boys are imputing more then is warranted with CO2
being
the causal agent. Are they epoptes initiates as well?
Or drinking from tax crack addiction?
Let's end the endless GOV borrowing for needless power trips.
http://en.wikipedia.org/wiki/Eleusinian_mysteries#End_of_the_Eleusinian_Mysteries
Back on TRACK--------->
Nine hits for guanylhydrazone + psoriasis
http://www.ncbi.nlm.nih.gov/pubmed?term=guanylhydrazone%20psoriasis&itool=QuerySuggestion
The first or most recent is rather salient.
www.ncbi.nlm.nih.gov/pubmed/15290341
2004 Jul;26(4):353-65. Epub 2004 Apr 26.
Inhibitors of polyamine metabolism: review article.
Wallace HM, Fraser AV.
Department of Medicine, University of Aberdeen, Polwarth Building,
Foresterhill, Aberdeen, Scotland, United Kingdom.
h.m.w...@abdn.ac.uk
The identification of increased polyamine concentrations in a variety
of diseases from cancer and psoriasis to parasitic infections has led
to the hypothesis that manipulation of polyamine metabolism is a
realistic target for therapeutic or preventative intervention in the
treatment of certain diseases. The early development of polyamine
biosynthetic single enzyme inhibitors such as alpha-
difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone)
showed some interesting early promise as anticancer drugs, but
ultimately failed in vivo. Despite this, DFMO is currently in use as
an effective anti-parasitic agent and has recently also been shown to
have further potential as a chemopreventative agent in colorectal
cancer. The initial promise in vitro led to the development and
testing of other potential inhibitors of the pathway namely the
polyamine analogues. The analogues have met with greater success than
the single enzyme inhibitors possibly due to their multiple targets.
These include down regulation of polyamine biosynthesis through
inhibition of ornithine decarboxylase and S-adenosylmethionine
decarboxylase and decreased polyamine uptake. This coupled with
increased activity of the catabolic enzymes, polyamine oxidase and
spermidine/spermine N1-acetyltransferase, and increased polyamine
export has made the analogues more effective in depleting polyamine
pools. Recently, the identification of a new oxidase (PAO-h1/SMO) in
polyamine catabolism and evidence of induction of both PAO and PAO-h1/
SMO in response to polyamine analogue treatment, suggests the
analogues may become an important part of future chemotherapeutic and/
or chemopreventative regimens.
PMID: 15290341
How many times have i pushed polyamine craP on you in the P NG?
Try 82 returns for keyword: polyamines [in the p ng]
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=polyamines&qt_g=Search+this+group
Only four hits for guanylhydrazone
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=guanylhydrazone+&qt_g=Search+this+group
Let's inspect some of the terms from that 1984 abstract.
Did they KNOW the whole truth back then?
Or only a small part of it?
hint: I already posted an abstract that show where things got fuzzy.
LOL
Anyway...
Or better yet anywhey or sweet whey will slow the crap in your
colon...hint hint. LOL
Let's spy a few wiki's
diamine oxidase
http://en.wikipedia.org/wiki/Histamine#Synthesis_and_metabolism
Synthesis and metabolism
Histamine is derived from the decarboxylation of the amino acid
histidine, a reaction catalyzed by the enzyme L-histidine
decarboxylase. It is a hydrophilic vasoactive amine.
Once formed, histamine is either stored or rapidly inactivated.
Histamine released into the synapses is broken down by acetaldehyde
dehydrogenase. It is the deficiency of this enzyme that triggers an
allergic reaction as histamines pool in the synapses. Histamine is
broken down by histamine-N-methyltransferase and diamine oxidase. Some
forms of foodborne disease, so-called "food poisonings," are due to
conversion of histidine into histamine in spoiled food, such as fish.
<sniP>
adenosylmethionine decarboxylase
http://en.wikipedia.org/wiki/Adenosylmethionine_decarboxylase
SAMe or SAM-e
http://en.wikipedia.org/wiki/S-Adenosyl_methionine
http://en.wikipedia.org/wiki/Ornithine_decarboxylase
The enzyme ornithine decarboxylase (ODC) participates in the urea
cycle, and in the metabolism of glutathione and amino groups. In
humans, this protein has 461 amino acids and forms a homodimer.
Reaction
It catalyzes the decarboxylation of ornithine producing, as a result,
diamine putrescine:
<sniP>
======================
So as to square the circle and go for a psor point of the P NG.
ubiquitity *** (another new word for the state of being perpetually
FULL of CRAP and
not really knowing it, as life is what it is, and how would you
notice, like a fish in
water, if your TOTAL world view really knows is CRAP? AND your FULL
of it?
Like obama for instance. LOL
I'LL limit this to psor folks though the analogy with PALitical
partisan feather bedding does work. <G>
How many times for the evil ____Ubiquitous____ (TOXIN) and psoriasis:
313 hits in the psor group:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=Ubiquitous&hl=en&
How many of those are MINE:
175 hits for ubiquitous + randall
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=Ubiquitous+randall
How many times did i misPELL it?
16 but five of those aren't mine. LOL
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=Ubiquitious+&qt_g=Search+this+group
But at least 82 ubiquitous posts have LPS in them.
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=Ubiquitous+LPS
What is my most misPELLED word?
I know, but you know i do, so i won't tell you. LOL
So till i run the numbers like the gov should do i won't bother with
details.
Wow, just like liars in heat for tax crack addiction. LOL
randall... a boy has to have some mystery or is that a chick?