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Psoriasis--Depression-LEAKY Guts // Treat with WIT KIT

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randall

unread,

Jul 4, 2008, 8:35:45 PM7/4/08

Hi,

Are you depressed because you have P?

Or does the TNF-- alpha that makes P cause the depression?

http://www.sciencenews.org/view/feature/id/33835/title/Sick_and_down
Sick and down
By Amy Maxmen

To fight off an infection or illness, the body shifts into a slow-down
mode that mirrors some symptoms of depression. In fact, scientists now
think the immune response itself may even cause the mood disorder.

[...]
Certain immune proteins in the body appear to mess with the minds of
otherwise healthy, but depressed people as well. Those who suffer from
major depression have higher levels of cytokines, immune proteins the
body makes to fend off infections and to patrol the body for disease,
and which laboratories mimic. Excess cytokines have also been found
lurking in the postmortem brains of suicide victims. “It raises the
issue, how much of how we feel — how much of who we are as people — is
dictated in terms of our immune system?” says Miller, a researcher at
Emory University in Atlanta.

[...]

Connecting body to mind

Like army generals, innate immune cytokines order inflammatory
molecules to prepare for war when the body is under threat from
invasive bacteria or viruses, or under perceived threat in the form of
stress or chronic disease. In these situations, cytokine levels rise.
“It’s a good thing if you’re running from a tiger,” explained
psychiatrist Dominique Musselman in May at a meeting in Washington,
D.C., of the American Psychiatric Association. “You’d want to rev up
your immune system to prepare for an injury.” Nowadays, however, angry
bosses, aggressive creditors and disappointed spouses have replaced
vicious predators, she said. And as those stressors are less likely to
bite, the subsequent immune response, which had evolved to heal
injuries and fight infection, seems a vestige of the distant past.

“The fact that stress can activate the innate immune response has been
a major breakthrough,” Miller notes. Add this to one more piece of the
puzzle: Stress often leads to depression. The immune system may
explain why.

In mapping out the molecular pathway between elevated cytokines in the
body and chemical changes in the brain, scientists aim to provide
targets for drugs intended to treat depression caused by inflammation.
In the last few years, researchers have identified primary suspects.
Many cytokine proteins, including tumor necrosis factor-alpha,
interleukin-6 and the type 1 interferons (IFN-alpha and IFN-beta),
have been accused of being the principal perpetrators in sickness
behavior. They respond rapidly to foreign intruders, circulate in the
bloodstream and initiate a response in the central nervous system.

Cytokines manufactured in the body can send messages through the
central nervous system to induce production of cytokines in the brain.
That message may be relayed when cytokines sneak into the brain
through leaky regions in the blood-brain barrier, a series of
structures that block most substances. In the brain, cytokines
activate inflammatory middlemen who tag-team their way to affecting
emotion-regulating neurotransmitters. As neurotransmitter levels
change, so can mood. “Among other things, we see a drop in levels of
serotonin, the feel-good chemical,” Miller says.

Attempts are underway to treat depression by blocking specific
cytokines or the messages they send. A 2006 clinical trial funded in
part by the biotech company Amgen found that depressed patients who
suffered from ___________psoriasis___________, an autoimmune skin
disease associated with increased levels of cytokines, felt happier
after taking the cytokine blocker etanercept (brand name Enbrel),
which affects tumor necrosis factor-alpha. Another TNF-alpha blocker,
infliximab (Remicade), is being tested for use in depressed patients
who don’t respond to antidepressants such as the selective serotonin
reuptake inhibitors Prozac and Zoloft. Those results should be ready
by 2010, says Charles Raison, a research psychiatrist at Emory
University who heads the project.

Anti-inflammatory drugs like aspirin and ibuprofen haven’t been shown
to affect mood. But another anti-inflammatory, celecoxib (Celebrex),
that more specifically blocks the inflammatory molecule COX-2, helped
heal depression in a small clinical trial in Germany. Norbert Müller,
a psychiatrist on that study from Ludwig-Maximilians-University
Munich, suggests that a high dose of aspirin would be needed to
inhibit COX-2 as strongly as celecoxib. And that, he says, “would
provoke a high rate of side effects, mainly gastrointestinal pain and
possibly bleeding.”

<sniP>

http://www.sciencenews.org/view/download/id/33845/name/From_Sick_to_Down

text for the above illustration
http://www.sciencenews.org/view/access/id/33845/name/sick-down.jpg

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

As an aside to the above, by taking excess aspirin the Gi track
bleeding is creating an
open invitation of even MORE systemic TNF-alpha.

Surely an auto looP that one doesn't want to perpetuate for long. :(
Unless you love the creation of more psoriasis.

00000000000000000000000000000000000000000000000000000000000000000000000000

Let's recaP.

Leaky guts allow LPS (endotoxins) to gain systemic entry from the
Gastrointestinal tract.

Then TNF is created...

http://www.nature.com/clpt/journal/v81/n3/images/6100114i2.jpg

http://www.endotext.org/adrenal/adrenal28/figures28/figure1.jpg
A Th1 skew is created by the increased polarization.
http://www.endotext.org/adrenal/adrenal28/adrenal28.htm

Search keywords: TNF depression

http://pmid.us/tnf+depression (573 hits on pubmed)

#3 in that search:
http://www.ncbi.nlm.nih.gov/pubmed/18580840?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The cytokine hypothesis of depression: inflammation, oxidative &
nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive
treatments in depression. Minireview.
Maes M.

Clinical Research Center for mental Health (CRC-MH ), Olmenlaan 9,
2610 Wilrijk, Belgium.

This paper hypothesizes that inflammatory, oxidative and nitrosative
(IO&NS) pathways, and an increased translocation of LPS from gram-
negative bacteria are causally related to depression following
external (psychological) and internal (organic) stressors and that
IO&NS pathways are novel targets for antidepressant development. We
review that depression is accompanied by an inflammatory reaction as
indicated by an increased production of pro-inflammatory cytokines,
such as interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-
alpha (TNF-alpha) and interferon-gamma (IFN)-gamma. These cytokines
are stress-sensitive and may cause depressive behaviors. The latter
may be induced by an increased catabolism of tryptophan, the precursor
of serotonin, to neurotoxic TRYCATs (tryptophan catabolites along the
indoleamine oxidase pathway). Inflammatory biomarkers are detected in
animal models of depression. Newly developed animal models of
depression are based on induced inflammation. Most if not all
antidepressants have specific anti-inflammatory effects. Anti-
inflammatory compounds may augment the clinical efficacy of
antidepressants. Depression is also accompanied by an IgM-related
(auto)immune response directed against disrupted lipid membrane
components, such as phosphatidyl-inositol, by-products of lipid
peroxidation, e.g. azelaic acid and malondialdehyde, and NO-modified
amino-acids, which are normally not detected by the immune system but
due to damage caused by O&NS have become immunogenic. Increased
translocation of ___________lipopolysaccharide__(lps)______ from
_______gram-negative bacteria_____, which may be induced by internal
and external stressors, may further aggravate the induced IO&NS
pathways. Future research to disentangle the complex pathophysiology
of depression calls for a powerful paradigm shift, i.e. using a high
throughput screening according to the translational medicine
methodology.

PMID: 18580840

LPS from endogenous endotoxin creates the TNF once it gains systemic
entry from a LEAKY GUT.
http://en.wikipedia.org/wiki/Lipopolysaccharide
http://en.wikipedia.org/wiki/Tnf

This permeability is in the gut, the HOT ZONE and by using sweet whey
(rich in galactose) the good
bacteria is fed and will block that leaky area. Hopefully anyway...

So you do the wit kit and stop being depressed and get rid of your
psoriasis in the BARGAIN... LOL
http://www.thewholewhey.com/Item10.htm

Lets add in one more term to the above search.

http://pmid.us/tnf+depression+probiotic

http://www.ncbi.nlm.nih.gov/pubmed/18456279?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The probiotic Bifidobacteria infantis: An assessment of potential
antidepressant properties in the rat.
Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG.

Department of Psychiatry and Alimentary Pharmacobiotic Centre,
Biosciences Institute, University College Cork, Cork, Ireland.

It is becoming increasingly apparent that probiotics are important to
the health of the host. The absence of probiotic bacteria in the gut
can have adverse effects not only locally in the gut, but has also
been shown to affect central HPA and monoaminergic activity, features
that have been implicated in the aetiology of depression. To evaluate
the potential antidepressant properties of probiotics, we tested rats
chronically treated with Bifidobacteria infantis in the forced swim
test, and also assessed the effects on immune, neuroendocrine and
central monoaminergic activity. Sprague-Dawley rats were treated for
14days with B. infantis. Probiotic administration in naive rats had no
effect on swim behaviours on day 3 or day 14 following the
commencement of treatment. However, there was a significant
attenuation of IFN-gamma, TNF-alpha and IL-6 cytokines following
mitogen stimulation (p<0.05) in probiotic-treated rats relative to
controls. Furthermore, there was a marked increase in plasma
concentrations of tryptophan (p<0.005) and kynurenic acid (p<0.05) in
the bifidobacteria-treated rats when compared to controls.
Bifidobacteria treatment also resulted in a reduced 5-HIAA
concentration in the frontal cortex and a decrease in DOPAC in the
amygdaloid cortex. The attenuation of pro-inflammatory immune
responses, and the elevation of the serotonergic precursor, tryptophan
by bifidobacteria treatment, provides encouraging evidence in support
of the proposition that this probiotic may possess antidepressant
properties. However, these findings are preliminary and further
investigation into the precise mechanisms involved, is warranted.

PMID: 18456279

The wit kit from thewholewhey.com is the fastest and easiest way to
change
your gut terrain from alkaline to slightly acidic in less then a
month.

In that amount of time your psoriasis clears up very nicely.

Happy 4th of July....!

randall... will any one step uP to the state of being CLEAR?

zzznot

unread,

Jul 4, 2008, 10:55:18 PM7/4/08

Huh. As if the situation itself
weren't depressing enuf.

"randall" <ranh...@aol.com> wrote in message
news:ae5a77f1-3355-4991...@a70g2000hsh.googlegroups.com...
Hi,

Are you depressed because you have P?

Or does the TNF-- alpha that makes P cause the depression?

http://www.sciencenews.org/view/feature/id/33835/title/Sick_and_down
Sick and down
By Amy Maxmen

issue, how much of how we feel?-?how much of who we are as people?-?is

randall

unread,

Jul 4, 2008, 11:52:39 PM7/4/08

On Jul 4, 7:55 pm, "zzznot" <zzz...@verizon.net> wrote:
> Huh. As if the situation itself
> weren't depressing enuf.
>
> J.
>

Think about it.

I've been mild, moderate and severe for 50 years.

And i'm totally happy. Even now more so then ever.

If it hadn't been for the wit kit, i may be singing the P blues. :(

I'm watching Jimmy Smits and the 4th special right now.

And their playing huey lewis and the power of love,
http://www.youtube.com/watch?v=wFaXTcR4dtE
(let it cue for a few minutes and then move the
cursor ahead about 28% of the way...)

Why would I be ecstatic without LSD or shrooms?

Some gene for inborn ecstasy? Real lucky if so. :)

I'm NO monk. I live in the real world for the most part.

Other pathways must kick in that re-supply
the opioids for the brain?
http://en.wikipedia.org/wiki/Opioids
Or is it even possible to be blissful without them?

Tell me doctor,
http://www.youtube.com/watch?v=-TTglhq6aA0&NR=1
Take me away, but promise i'll be back in time..... :)

Otherwise why would I still be alive? How did mother Teresa
do it? http://en.wikipedia.org/wiki/Mother_Teresa

My father, I saw him today, has a few percent pasi on his
legs and he's pushing 90.
While I know he LOVEs his children and wife and THEY are worth living
for, he
still has that other MAGIC sPark. The one beyond being.

Going by reality, and being his son and being so totally screwed
by that role of HIS genetic dice, and even so artifully compensating
for mother
nature, which I must admit I do better then anyone on the Planet, i'm
OK...................... :)

More then OK... and

Actually quite a bit better...

randall... has a grasP...& has P.. on the 4th... :)

manfred

unread,

Jul 5, 2008, 9:11:23 AM7/5/08

http://www.wjgnet.com/1007-9327/14/2029.asp

ISSN 1007-9327 CN 14-1219/R World J Gastroenterol 2008 April 7;
14(13): 2029-2036

Probiotic intervention has strain-specific anti-inflammatory effects
in healthy adults

From the discussion:

<snip>

We found that L. rhamnosus GG was also able to reduce pro-inflammatory
TNF-a production in the Gram-positive bacteria-stimulated PBMC. TNF-a
is secreted by the monocytes, and it acts as an inflammatory mediator
activating many types of cells. In our previous work with leukocyte
cell culture, L. rhamnosus GG was found to be a relatively poor
inducer of TNF-a, IL-12, IFN-g and IL-10[17]. Our present findings are
supported by another clinical study carried out in healthy adults
showing that L. rhamnosus GG treatment leads to decreased TNF-a
production in PBMC[31]. In addition, when the cytokine expression
pattern in the small bowel mucosa was studied, it was found that L.
rhamnosus GG induced the expression of genes involved in immune
response and inflammation (TGF-beta and TNF family members, cytokines,
nitric oxide synthase 1, defensin alpha 1)[32]. Schultz and
coworkers[31] observed a decreased IL-6 and IFN-g and an increased
IL-10 and IL-4 production in PBMC obtained from L. rhamnosus GG
treated individuals. We, however, did not find any significant changes
in bacteria-induced production of cytokines apart from the TNF-a in
the PBMC cultures of our study subjects after L. rhamnosus GG
treatment. In another study with healthy adults and with patients with
Crohn’s disease, L. rhamnosus GG decreased the production of IL-2,
IL-10 and IL-4 from PBMCs sorted as naïve and memory T cells[33]. It
seems that L. rhamnosus GG has a role in modulating the cytokine
responses and may possess an anti-inflammatory potential in healthy
individuals

<snip>

randall

unread,

Jul 10, 2008, 12:33:35 PM7/10/08

> ___________IL-10_______and IL-4 from PBMCs sorted as naïve

> and memory T cells[33]. It
> seems that L. rhamnosus GG has a role in modulating the cytokine
> responses and may possess an anti-inflammatory potential in healthy
> individuals
>
> <snip>

Manfred,

Thanks for your inPut.

Check this one out. While i've been a proponent to get to the
roots of the gut, I didn't expect this next story.

Know how we've been told that the appendix is some extraneous
organ or vestigial left over from evolution or something? LOL

Well.... it's a dive for good bacteria it turns out. Or might be. <g>

http://www.nytimes.com/2008/06/17/health/research/17appe.html?ref=science

Helpful Bacteria May Hide in Appendix
By NICHOLAS BAKALAR
Published: June 17, 2008
Everyone is born with one, but no one knows what it’s for. The human
appendix is a small dead-end tube connected to the cecum, or ascending
colon, one section of the large intestine. Everyone lives happily with
it until it becomes painfully inflamed, when the only treatment is to
remove it surgically.

Then everyone lives happily without it. So why is it there in the
first place?
Some experts have guessed that it is a vestige of the evolutionary
development of some other organ, but there is little evidence for an
appendix in our evolutionary ancestors. Few mammals have any appendix
at all, and the appendices of those that do bears little resemblance
to the human one.
Last December, researchers published a novel explanation in The
Journal of Theoretical Biology. The appendix, they suggest, is a “safe
house” for commensal bacteria, the symbiotic germs that aid digestion
and help protect against disease-causing germs.
Structurally, the appendix is isolated from the rest of the gut, with
an opening smaller than a pencil lead, protected from the fecal stream
that might be carrying pathogens. In times of trouble like a diarrheal
infection that flushes the syst em, these commensal bacteria could
hide out there, ready to repopulate the gut when the coast is clear.
William Parker, the senior author of the study and an assistant
professor of surgery at Duke, emphasized that this was a hypothesis,
not experimental proof. “At this point,” Dr. Parker said, “this is a
deduction based on a lot of information that we’ve had for many years
and some key pieces of information that have only been uncovered
recently by our lab and others. It does make sense.
“But an experiment to prove this theory would be very expensive. And
in any case, why would you want to spend money to find out something
that is not likely to help cure a disease?”
Rebecca E. Fisher, an assistant professor of anatomy at the University
of Arizona College of Medicine, said that although the appendix was
“likely to be a derived feature, selected for a purpose, the enigma is
that we didn’t know what that purpose might be.”
“I think Parker’s study offers an interesting solution,” Professor
Fisher said.
Recent studies have found that biofilms, colonies of beneficial
microbes that live outside cells, form in the large intestine, where
they are dependent on the mucus that lines the bowel. There, they aid
digestion and protect ag ainst infection, while enjoying the
protection and nutrition of the human host.
The researchers, examining tissue from uninfected human appendices
removed in kidney-pancreas transplants, found biofilms on the
epithelial lining of the appendix, as well. Under their theory, it is
in these biofilms in the appendix, well positioned to avoid pathogens
in the rest of the gut, that commensal bacteria take refuge.
If that is true, why is it that removing the appendix apparently does
not have negative side effects? The scientists contend that in
industrialized countries with modern medical care and sanitation,
maintaining a reserve of helpful bacteria has become unnecessary.
Widespread outbreaks of intestinal disease are so rare that the
commensal bacteria face little danger of extermination.
Dr. Parker wants to know whether biofilms function in the same way in
other animals. “We already have an idea that the cecum in some animals
works the same way,” he said. “But how, for example, do biofilms work
in frogs and other species with no cecum and no appendix?”
Whether the human appendix has the function Dr. Parker thinks it has
or whether it has no function at all, it is clear, he said, that “if
your appendix gets inflamed, forget about the fact that it might have
some function.”
“You have to get it out,” he added. “Appendicitis can be life
threatening, and the earlier you treat it, the less likely it is that
you will die from it.”

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

Let's find the Dr. Parker abstract...

OK..

http://www.ncbi.nlm.nih.gov/pubmed/17936308?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Biofilms in the large bowel suggest an apparent function of the human
vermiform appendix.

Randal Bollinger R, Barbas AS, Bush EL, Lin SS, Parker W.

Department of Surgery, Duke University Medical Center, Box 2605,
Durham, NC 27710, USA.

The human vermiform ("worm-like") appendix is a 5-10cm long and
0.5-1cm wide pouch that extends from the cecum of the large bowel. The
architecture of the human appendix is unique among mammals, and few
mammals other than humans have an appendix at all. The function of the
human appendix has long been a matter of debate, with the structure
often considered to be a vestige of evolutionary development despite
evidence to the contrary based on comparative primate anatomy. The
appendix is thought to have some immune function based on its
association with substantial lymphatic tissue, although the specific
nature of that putative function is unknown. Based (a) on a recently
acquired understanding of immune-mediated biofilm formation by
commensal bacteria in the mammalian gut, (b) on biofilm distribution
in the large bowel, (c) the association of lymphoid tissue with the
appendix, (d) the potential for biofilms to protect and support
colonization by commensal bacteria, and (e) on the architecture of the
human bowel, we propose that the human appendix is well suited as a
"safe house" for commensal bacteria, providing support for bacterial
growth and potentially facilitating re-inoculation of the colon in the
event that the contents of the intestinal tract are purged following
exposure to a pathogen.

PMID: 17936308

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

I've only talked about good microbiota (commensal bacteria) to block
LPS
(endogenous endotoxin) from systemic entry a million times. :)

Plus with some really good genetically altered microbiota, we may be
able
to dial in some level of IL-10 to stop the polarization (Th1 skew) of
all
autoimmune conditions. Not to just mention psoriasis.

Here's a drug that may be helpful.

It hinders lps--->TNF. And we know that would slow TNF creation etc.

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

http://www.foxbusiness.com/story/markets/industries/health-care/compugen-announces-positive-vivo-results-therapeutic-peptide-candidate-immune/

TEL AVIV, Israel, Jul 09, 2008 (BUSINESS WIRE) ----Compugen Ltd.
(NASDAQ:CGEN) announced today positive results from a recently
completed in vivo study of CGEN-25007, a novel peptide antagonist of
the gp96 protein. The data indicate that CGEN-25007 has
immunosuppressive effects and therapeutic potential for the treatment
of various inflammatory diseases and other immune related pathologies.
CGEN-25007, which has been shown to bind to recombinant gp96 in a dose
dependent manner, was initially predicted using the Company's
previously announced DAC blockers platform, which was designed to
predict peptides that block proteins of interest from achieving
certain disease-associated conformations.

Using an animal model of endotoxemia, a condition in which there is a
substantial increase in the levels of inflammatory cytokines and
chemokines in serum, CGEN-25007 was shown to exhibit a profound and
dose-dependent anti-inflammatory activity. In this study, the novel
peptide was administered following the introduction of
lipopolysaccharide (LPS: 31.69, +0.08, +0.25%), a bacterial substance
that induces a strong response in the animal immune system leading to
systemic inflammation. The administration of CGEN-25007 resulted in a
decrease of approximately 50% in the serum levels of inflammatory
cytokines and chemokines, including tumor necrosis factor alpha (TNF-
(alpha)), IL-6, interferon-gamma (IFN-(gamma)), MIP-1(alpha) and
MIP-2.

In addition, in ex-vivo experiments CGEN-25007 was found to strongly
inhibit the secretion of inflammatory cytokines from human peripheral
blood mononuclear cells (PBMCs) which had been challenged with LPS,
staphylococcus epidermidis or anti-CD3 antibody, compounds known to
activate the human immune system through different receptors. PBMCs
triggered with these compounds and treated with CGEN-25007 exhibited
more than 80% inhibition of secretion of cytokines, including
TNF(alpha), IL-1(beta), IL-6, IL-8, IL-12 and MIP-1(alpha). In
addition, CGEN-25007 had only a 20% inhibitory effect on the secretion
of GM-CSF and no effect on the secretion of IL-2, suggesting
selectivity in the action of this peptide.

These results support the potential use of this peptide as a novel
approach for the treatment of many immune related diseases, including
sepsis, autoimmune disorders, cardiovascular diseases and acute
transplant rejection.

Yossi Cohen, M.D., Compugen's Vice President of Research and
Development, said, "Reduction of certain inflammatory cytokines and
chemokines in serum is the primary target of many anti-inflammatory
drugs. As such, we are looking forward to continuing the development
of this novel peptide which has now shown therapeutic potential for
several important medical conditions. In addition, we are extremely
pleased by this further validation of the ability of our DAC Blockers
platform to predict peptides that can target and block disease-
associated conformations of proteins. Additional peptides, targeting
two other proteins and predicted in the pilot run of the platform to
be conformation blockers, are now undergoing initial experimental
evaluation."

About gp96

The gp96 protein triggers both the innate and adaptive arms of the
immune system and its importance in inflammatory responses has been
demonstrated in recent years. Through its involvement in the innate
branch of immunity, gp96 potentiates responsiveness for Toll-like
receptors (TLRs) on antigen presenting cells (APCs). TLR activation on
APCs induces a pro-inflammatory response, including cytokine secretion
and expression of co-stimulatory molecules, which in turn recruit and
activate T cells. In addition, gp96 enables specific immune responses
by transferring immunogenic peptides to MHC class I molecules, thus
facilitating antigen specific activation of cytotoxic T cells. These
key roles make gp96 an important target for therapeutic intervention
in the treatment of immune-related disorders.
<sniP>

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