Google Groups no longer supports new Usenet posts or subscriptions. Historical content remains viewable.

Dismiss

PART II -->Dick Gallo - Hygiene Hypothesis (hh)-->Th2 <-- plus a bunch more (human holobionts) = EnteroTypes

2 views

Skip to first unread message

randall

unread,

May 12, 2011, 4:34:50 PM5/12/11

part II

How do i shake me uP to LIVE LONG?

I don't wanna do five zillion jumPing jacks and then die at 96 due to
pneumonia?

Do you?

NO...

I'm taking www.longevinex.com when i stop doing my TRIALs to cure
psoriasis and other autoimmune disEASE.

RESVERATROL looks better every DAY. Under the bough with thou and a
mug of good bugs. LOL

http://www.wellnessresources.com/health/articles/resveratrol_reduces_alzheimers_brain_plaques/
Resveratrol Reduces Alzheimer’s Brain Plaques

Monday, January 31, 2011 - Byron Richards, CCN

Resveratrol has received considerable attention for its anti-aging
properties involving the activation of the SIRT1 gene. Another aspect
of resveratrol function is to activate the production of friendly
nitric oxide in your brain. This offers a way to prevent the cascade
of free radical damage that leads to plaque formation.

Friendly nitric oxide is called eNOS (endothelial nitric oxide). eNOS
enables blood to flow through your circulation. When eNOS production
is disrupted, problems with blood pressure, cholesterol, and blood
sugar are much more common. These problems induce further depression
of eNOS causing a vicious catch 22. In essence, free radical
production jumps into high gear and can start making the most damaging
of all free radicals, peroxynitrite.

Resveratrol has now been found to activate the enzyme that helps make
friendly eNOS, thereby breaking the catch 22. Interestingly, other
researchers have just shown that the formation of Alzheimer’s plaque
actually depresses eNOS, in turn leading to more plaque. In an animal
study, researchers show that resveratrol significantly inhibits plaque
formation in animals genetically altered to develop Alzheimer’s (up to
90% reduction in plaque formation).

This new information suggests that resveratrol—along with blueberries
and grape seed extract—is another potent nutrient to add to the
expanding list of nutrients that help to protect and preserve healthy
brain function.
<snip>

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

Eating LOW on the HOG to knock those BUGs right out of your LIFE:

http://www.wellnessresources.com/health/articles/quercetin_lowers_respiratory_inflammation_activates_sirt1/
Quercetin Lowers Respiratory Inflammation, Activates SIRT1

Sunday, January 30, 2011 - Byron Richards, CCN

In a recent study, mice were given toxins to produce lung damage that
mimicked chronic obstructive pulmonary disease (COPD) and emphysema.
Quercetin treatment for 10 days significantly improved the lungs,
reducing free radical damage and inflammation. It also upregulated
the longevity gene SIRT1—this is the first time quercetin has been
shown to activate this gene.

While many current and former smokers wind up with COPD, many others
are suffering from excess pollution and various common chemical
exposures. When the lungs become a weak spot, they are more
susceptible to infections that can linger. It is also more difficult
to get oxygen into your body, handicapping health at a fundamental
level.

When the researchers blocked SIRT1 activation, quercetin was no longer
able to protect the lungs. This is a novel finding and indicates an
additional potent mechanism by which quercetin may help extend the
survival of stressed cells in your sinuses and lungs.
<snip>

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

Take out the trash, yakity yak don't TALK BACK?

Which means?

----

http://www.wellnessresources.com/health/articles/fisetin_for_neuro-protection/
Fisetin for Neuro-Protection
Thursday, November 11, 2010 - Byron Richards, CCN

Fisetin is a unique polyphenol flavonoid that has demonstrated a high
level of neuro-protection along with improvement of memory. A
standardized extract of fisetin is now undergoing extensive scientific
studies by the Salk Institute for Biological Studies to prove its
value for general brain health. A patent has already been issued,
entitled “Methods of Using Flavonoids to Enhance Memory.” It appears
that fisetin is another useful nutrient tool in the preservation of
cognitive well being.

Fisetin is found in small amounts in many fruits and vegetables
including mangoes and strawberries, although the standardized extract
comes from the Japanese Wax Shrub/Tree (Rhus succedanea – L). There
are thousands of polyphenols in nature with some having structures
that are highly bioactive. Examples include the anthocyanins of
blueberries, quercetin, grape seed extract, resveratrol, green tea
catechins, etc. In general such nutrients have antioxidant, anti-
inflammatory, and gene-regulating attributes – in other words they are
vital to human health.

Researchers came upon fisetin during a screening process of many
natural substances, looking for nutrients that could prevent oxidative
stress from causing nerve cell death. Oxidative stress to nerve cells
is a common problem in today’s society and always occurs in situations
of cognitive impairment and decline. Protection of nerves is a top
priority for health, as nerves regulate everything else and once they
start to have trouble health declines.

We now know that the unique structure of each polyphenol flavonoid
means that it may influence different gene pathways relating to nerve
function and protection. This is why it is good to have a mix of
these types of nutrients in your supplements. For example, the core
cellular antioxidant, glutathione, is influenced by many flavonoids
and nutrients like grape seed extract, R alpha lipoic acid,
tocotrienol E, and NAC. Fisetin operates in a very specific pathway1
to boost nerve cell glutathione levels and to reduce one of the most
damaging free radicals, peroxynitrite.

Researchers have now documented a number of additional ways in which
fisetin protects nerve cells during the aging process. They have
shown that it can protect nerve cells from damage during toxin-induced
stroke3 – while at the same time maintaining the vital production of
energy in the brain (ATP synthesis was preserved). Excessive
activation of the glial cells in the brain is associated with
inflammatory nerve damage, excitotoxicity, and declining neurological
health. Fisetin has been shown to reduce excess glial cell
activation4 upon exposure of nerve cells to a known neurotoxin.
Fisetin has also been shown to reduce excessive formation of amyloid
beta protein5 – a process that otherwise induces brain plaque
associated with cognitive decline.

In addition to nerve protection, fisetin has been shown to boost the
activity of gene pathways6 involved in the improvement of memory. In
fact, data shows that fisetin stimulates the growth of new nerve
cells7 – a form of nerve rejuvenation.

Collectively these studies demonstrate that fisetin is a nutrient that
influences multiple pathways in a positive way so as to protect the
brain. Since the type of help fisetin offers is related to factors
that worsen with age, the preliminary body of science suggests that
fisetin is a novel brain anti-aging nutrient.

<snip>

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

Someone besides i, is mad at big pharma?

Why, why, why? (rodney king or nancy kerrigan/ and why not co-operate
or be nice with one another?)

Are they also unCURABLE like i?

I dunno.

Let's see:

http://www.wellnessresources.com/freedom/articles/drug_marketing_injures_patients/
Drug Marketing Injures Patients
Saturday, January 29, 2011 - Byron Richards, CCN

<snip>

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

Heck their gonna cure HIV with small molecules before psoriasis.

So take that BIG Pharma...

oh wait.. they want that? right?

Or was it just some guys at scriPPs getting all smart and aLL?

http://www.nctimes.com/app/blogs/wp/?p=11966

Scripps Research Details HIV Capsid Structure, Potential Drug
By: Bradley Fikes — January 19th, 2011

HIV is the subject of a duo of papers this week from Scripps Research
Institute scientists.

The first concerns newly created compounds that inhibit HIV
replication and fight inflammation. It was published in in the
Proceedings of the National Academy of Sciences.

The second is a technical feat: an atomic-scale modelling of the HIV
capsid, the cone-shaped protein container the virus injects into human
cells. The capsid contains the genetic instructions for hijacking the
infected cell to make more HIV particles. It was published in Nature.
(Abstract: Subscription or payment required to read full text).

The capsid of HIV is a conical fullerene shell that comprises about
250 hexamers (orange) and exactly 12 pentamers (gold) of the viral CA
protein. In the new study, the researchers determined X-ray crystal
structures of these building blocks, which enabled modeling of the
complete capsid at atomic resolution. The continuously varying lattice
curvature in the fullerene cone can be explained simply by two rigid
body rotations around two assembly interfaces of CA. (Graphics by Owen
Pornillos, Barbie Ganser-Pornillos, Kelly Dryden, and Mark Yeager.)

The first paper results from a study of the plant Hypericum chinense,
known in Japan as biyouyanagi. The flower-bearing plant makes
chemicals known as biyouyanagins known to have anti-HIV and anti-tumor
properties. The plant is from the same family that produces St. John’s
wort.

Those properties piqued the curiosity of TSRI chemistry wizard K.C.
Nicolaou, according to a Scripps press release. Nicolaou is chair of
the department of chemistry, Aline W. and L.S. Skaggs Professor of
Chemical Biology, and Darlene Shiley Chair in chemistry. His lab is
known for a number of accomplishments over the years, such as the
total synthesis of the cancer drug Taxol.

K. C. Nicolaou
The newly discovered biyouyanagins are small molecules, which are more
easily administered orally than large molecules, such as proteins,
which usually have to be injected.

The scientists plan to tweak one especially promising chemical into a
drug candidate. If it passes lab and animal studies, the drug will be
tested in humans.

The second paper “Atomic Level Modeling of the HIV Capsid”, was
prepared by a research team from TSRI and the University of Virginia.
The study’s senior is author Mark Yeager, a TSRI professor and staff
cardiologist and chair of the Molecular Physiology and Biological
Physics Department at The University of Virginia School of Medicine.

According to the TSRI press release:
“The work is the culmination of studies carried out over the last
decade looking at different portions of the cone-shaped container, or
the capsid. The final piece of the puzzle, described in an article
published in Nature on January 20, 2011, details the structure of the
two ends of the cone ….
Having solved the atomic structures of both CA hexamers and pentamers,
Yeager and colleagues for the first time were able to build a complete
atomic model of the mature HIV capsid.
The researchers now plan to further refine the model using
sophisticated computer programs to determine the stability of the
structure in different regions and to identify possible “weak” points
they can target using newly designed drugs.
They will also begin studying the structure of the immature capsid to
determine how this version of the capsid transitions to the mature form
—a step in the virus lifecycle that has remained mysterious.
“We don’t have the full story yet, but we have volume one,” says
Yeager.”

The paper was funded by the U.S. National Institutes of Health and by
P50 funding from the Center for the Structural Biology of Host
Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH), which
is based at the University of Utah

http://www.ncbi.nlm.nih.gov/pubmed/21245351

Proc Natl Acad Sci U S A. 2011 Jan 20.
Organic Synthesis Toward Small-Molecule Probes and Drugs Special
Feature: Design, synthesis, and biological evaluation of a
biyouyanagin compound library.

Nicolaou KC, Sanchini S, Sarlah D, Lu G, Wu TR, Nomura DK, Cravatt BF,
Cubitt B, de la Torre JC, Hessell AJ, Burton DR.

Department of Chemistry, Skaggs Institute for Chemical Biology,
Department of Chemical Physiology, Department of Immunology and
Microbial Science, and International AIDS Vaccine Initiative
Neutralising Antibody Center, The Scripps Research Institute, 10550
North Torrey Pines Road, La Jolla, CA 92037.

Abstract
Modern drug discovery efforts rely, to a large extent, on lead
compounds from two classes of small organic molecules; namely, natural
products (i.e., secondary metabolites) and designed compounds (i.e.,
synthetic molecules). In this article, we demonstrate how these two
domains of lead compounds can be merged through total synthesis and
molecular design of analogs patterned after the targeted natural
products, whose promising biological properties provide the
motivation. Specifically, the present study targeted the naturally
occurring biyouyanagins A and B and their analogs through modular
chemical synthesis and led to the discovery of small organic molecules
possessing anti-HIV and anti-arenavirus properties.

PMID: 21245351

Views of HIV caPsid:

http://www.pdb.org/pdb/explore/explore.do;jsessionid=DC405625ADDC2AF85E05E2D343B7CDBA?structureId=3P05
http://www.pdb.org/pdb/explore/explore.do?structureId=3P05

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

Treg time: (foxp3 by default)

http://www.eurekalert.org/pub_releases/2011-01/wjog-tli013111.php
T-regulatory lymphocytes in gastrointestinal cancer

T-regulatory lymphocytes (Tregs) are a subset of T lymphocytes that
are involved in the mechanism of immunotolerance to self- and allo-
antigens. Activity of these cells is one of the mechanisms of immune
evasion of tumors, which inhibits the antitumor activity of effector
cells. Tregs are among the tumor-infiltrating lymphocytes and
circulate in the peripheral blood. In various cancer types, increased
prevalence of Tregs has been observed, and in some studies, this has
been reported as a prognostic factor.

A research article published on January 21, 2011 in the World Journal
of Gastroenterology addresses this question. The authors studied the
peripheral blood Tregs as a potential disease marker, which was
relatively easy to measure during pretreatment and follow-up periods.

The results indicated that the absolute number of Tregs in peripheral
blood of gastric cancer but not colorectal cancer patients was
significantly decreased in comparison with that in healthy controls.
The findings suggest that the population of Tregs in peripheral blood
does not simply mimic stromal Tregs. Further studies on larger groups
of patients are necessary to evaluate the Treg population in cancer
patients.

###

Reference: Szczepanik AM, Siedlar M, Sierzega M, Goroszeniuk D,
Bukowska-Strakova K, Czupryna A, Kulig J. T-regulatory lymphocytes in
peripheral blood of gastric and colorectal cancer patients. World J
Gastroenterol 2011; 17(3): 343-348

http://www.wjgnet.com/1007-9327/full/v17/i3/343.htm

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

http://www.ncbi.nlm.nih.gov/pubmed/21253393
World J Gastroenterol. 2011 Jan 21;17(3):343-8.

T-regulatory lymphocytes in peripheral blood of gastric and colorectal
cancer patients.

Szczepanik AM, Siedlar M, Sierzega M, Goroszeniuk D, Bukowska-Strakova
K, Czupryna A, Kulig J.

Antoni M Szczepanik, Marek Sierzega, Antoni Czupryna, Jan Kulig, 1st
Department of General and Gastrointestinal Surgery, Jagiellonian
University Medical College, 31-501 Krakow, Poland.

Abstract
AIM: To assess the absolute number of T-regulatory cells (Tregs;
CD4(+)CD25(+)Foxp3(+)) in the peripheral blood of gastric and
colorectal cancer patients.

METHODS: We enrolled 70 cancer patients (33 gastric cancer, 37
colorectal cancer) and 17 healthy volunteers. The CD3(+)CD4(+)
lymphocytes and CD4(+)CD25(+)Foxp3(+) Tregs in the peripheral blood
were analyzed with flow cytometry. The absolute numbers of Tregs were
calculated based on the CD4(+)CD25(+)Foxp3(+) cells percentage of
CD3(+)CD4(+) cells and the absolute numbers of CD3(+)CD4(+) cells per
microliter.

RESULTS: The mean number of CD4(+)CD25(+)Foxp3(+) cells per microliter
in colorectal cancer patients was 15.7 (SD: 21.8), for gastric cancer
patients 12.2 (SD: 14.3), and for controls 17.5 (SD: 11.4). The
absolute number of Tregs was significantly lower in gastric cancer
patients than in controls (P = 0.026). There was no statistically
significant difference for gastric vs colorectal cancer or colorectal
cancer vs controls. The absolute number of Tregs was also
significantly depressed in N(+)vs N(-) cancer patients [22.0 (27.7) vs
10.1 (9.0), P = 0.013], and in the subgroup of gastric cancer patients
[30.3 (27.6) vs 9.6 (8.0), P = 0.003]. No statistical difference was
observed in the proportion of Tregs in the CD4(+) population between
the groups.

CONCLUSION: The absolute number of Tregs in peripheral blood of
gastric cancer but not colorectal cancer patients was significantly
decreased in comparison with that in healthy controls.

PMID: 21253393
free full text:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022294/?tool=pubmed

133 hits for primary author "Kulig J"[Author]- pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kulig%20J%22%5BAuthor%5D

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

What about human coral reef people who fall in love due to smells
given off, BEcause of their commensal microbes in GIT (gastro
intestinal tract)?

What? You mean fairy moans?

Do YOU mean pheromones?

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

Your the FAIRY, you moaning maniac. LOL

Yeah? Yeah, well check it out fairy airy juan:

sex and fairy moans:
http://www.sexanddrugs.info/pheromonesandsex.htm

OK back on track jack and what makes for pheromones and or fairy
moans:

This:

Posted last week:
Mon, Jan 24 2011 12:34 pm
LaLanne REMEMBERED - Magnesium - Mercola Metabolismisms -96 Y/O
Chester REED redux - Gut Bugs -L. Plantarum -SFB - TLR's -IL-10 AGAIN -
Curcumin - PILLs & Drugs - MIND pOWERs - IL10 & LPS
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_thread/thread/f7c23401483b22e9/69b0edf76c396c74?hl=en&lnk=gst&q=holobiont#69b0edf76c396c74
or
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/69b0edf76c396c74

[...]

http://www.sciencedaily.com/releases/2010/12/101202124211.htm
Do Our Bodies' Bacteria Play Matchmaker?

ScienceDaily (Dec. 3, 2010) — Could the bacteria that we carry in our
bodies decide who we marry? According to a new study from Tel Aviv
University, the answer lies in the gut of a small fruit fly.

<snip>

OK so how do gut bugs affect You as the human reef that harbors them?

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

The commensal relationship is tipping the SCALEs on being symbiotic:
http://en.wikipedia.org/wiki/Symbiotic

With the ability to direct the population of the 1000 bugs a person
can be built from the GUT uP.

http://en.wikipedia.org/wiki/Gut_flora#Acquisition_of_gut_flora_in_human_infants

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

So, now as human coral reefs (holobiont), we find that these
commensals may direct our AFFECTIONS
and AFFAIRs of HEART?

Is the GIT bug in us looking for a particular Gi BUG in your human
other LOvER?

Why NOT?

Bugs being 10 X's the cells in me are hooking up with the 10 X's bugs
over cells in YOU for what exactly?

Worming us to LOVE or some other ulterior motive?

Affair of the BUG to stay viable and become one flesh and BEEF uP
THEIR DNA with
the DNA of the other lover's BUGs/DNA?

Why not fall in love with LOVE and share with a TON of other LOVERs?

LUST for BUGs and to much foreign DNA might lead to buggy DNA/RNA over
LOADs?

To early to tell. But to many lovers and your all sharing a TON of
virals to boot.

Maybe that's the key?

The virals in you and me need a Th1 skew to unRULE their DAY in the
SUN?

The sunny uvb rays help LL37 to kill block those unRULY ones from
killing the symbiont?

OK---> so am i the clownfish or the sea anemone who eats his fecal
matter?
http://en.wikipedia.org/wiki/Symbiosis

Good JUAN.. & unWORMing your LIFE is strife and and an...

http://www.sciencenews.org/view/feature/id/68701/title/Worming_Your_Way_to_Better_Health
Worming Your Way to Better Health

To battle autoimmune disease and allergy, scientists tune in to the
tricks of parasitesBy Nathan Seppa January 29th, 2011; Vol.179 #3 (p.
26) Text Size Enlarge

Parasitic hookworms cling to the intestinal wall, living on human
blood. They may also keep inflammation at bay.© David Scharf/Science
Faction/CorbisBack in the bad old Stone Age, humans had to put up with
all sorts of creepy crawlies. Parasites ran amok in people’s innards,
freeloading on nutrient supplies. The parasites took a toll, but over
the millennia, those that killed off their meal ticket too quickly
didn’t make it. The survivors of this evolutionary shakeout include
parasitic roundworms and flatworms, hitchhikers that allow their human
host to live on — and to provide three hots and a cot.

While this scenario might appear to be win-lose, with humans the clear
losers, research now suggests that may not be the whole story. In
their drive to make humans hospitable hosts, parasites have developed
the ability to suppress inflammation aimed against them. And this, it
turns out, isn’t necessarily a bad thing

“They have evolutionarily adapted to this long-standing interaction
with their hosts — that’s us — and developed strategies to help the
host dampen its immune response,” says Helmut Haas, an immunologist at
the Research Center Borstel in Germany.

These strategies are not subtle. But humans have survived the effects
and even adapted well to them: A toned-down immunity is, perhaps, the
norm. A sober immune system might still defend against enemies while
not overreacting to everyday substances in the environment, or
otherwise going awry. Suddenly those prehistoric times don’t sound so
bad — no Crohn’s disease, no multiple sclerosis, no asthma. Good old
Stone Age.

In a stroke of medical inspiration as bold as it is counterintuitive,
scientists are now testing this theory by treating patients with live
microscopic eggs or larvae of parasitic worms designed to quell these
very afflictions. Several clinical research trials are under way and
more are planned. Whether promising early results will lead to
treatments for these known or suspected autoimmune conditions — and
extend to allergy, type 1 diabetes, psoriasis and other cases of
immune revolt — remains to be seen.

A marriage on the rocks

Parasitic worms, or helminths, elicit a visceral response from people
— in every sense. Worms don’t make for polite dinner conversation and,
in industrialized countries, are considered a relic of days thankfully
in the past. The notion that helminths are bad guys has been drummed
into children of Western nations for several generations, as well as
their doctors. (The Latin name for one hookworm is Necator americanus,
meaning American killer.)

But helminths have thrived in mammals for millions of years, fine-
tuning the parasite act along the way. “These parasites do some harm
to the host,” says immunophysiologist Derek McKay of the University of
Calgary in Canada. “But if I’m [a parasite] inside a host, at the very
least I want the host to reproduce and make more host babies, since my
babies will need hosts.”

Besides, an all-out immune war on a helminth might damage the gut.
“What we have instead is détente,” says David Elliott, a
gastroenterologist at the University of Iowa Carver College of
Medicine in Iowa City.

Only recently did the advent of better sanitation and potent drugs
break up this marriage. Shoe-wearing put hookworms out of business in
the United States. But the 20th century also ushered in asthma,
allergy and a host of autoimmune diseases that had been uncommon
previously and remain so in less developed countries. All are marked
by out-of-control immunity. Vanquishing worm parasites in particular
might have disrupted an equilibrium that had served humans well.

Changes in latitudes

Of course, parasitic worms have not really gone away. Some estimates
suggest that more than 1 billion people, mainly in the tropics, are
infected, giving scientists a chance to study the link between
immunity and parasites in context.

In 2003, researchers at the University of Nottingham in England and
colleagues found that toddlers living in an Ethiopian city were twice
as likely to wheeze — a symptom related to asthma — than were kids
living in less sanitary rural areas. Similarly, Ethiopian kids with
roundworm infections were half as likely to wheeze as those free of
parasitic worms.

At about that time in Argentina, physicians Jorge Correale and
Mauricio Farez began a small study that brought the helminth issue
into sharp focus. Studies had shown that mice with a disease similar
to multiple sclerosis, marked by damage to the fatty sheaths
insulating nerves in the central nervous system, improved when
infected with parasitic flatworms.

That prompted Correale and Farez to examine a group of MS patients and
identify 12, average age 34, who had recently acquired a parasitic
worm infection. Then the doctors found 12 other MS patients who
matched the first group in age and other respects, but who didn’t have
parasites. The rate of MS relapse, or symptom recurrence, had been
similar in both groups.

As part of the study, which followed patients for an average of 4.6
years, those harboring parasites agreed not to be treated for them.
Perhaps it’s just as well, because MS symptoms in this group became
mild to nonexistent. Only three of the patients had a relapse — one
apiece — during the study period. The other nine worm-infected
patients had none at all. In contrast, the MS patients without
parasites had 56 relapses in all, about one per year each. Relapses
were treated with prednisone, a steroid drug.

MRI scans, which can detect brain damage that might go unnoticed
otherwise, showed 14 brain lesions in the worm-infected patients
during the study and 164 in the other group. Mild anemia showed up in
four people with worms, but the other eight had no serious ill effects
from the parasites. The results appeared in the Annals of Neurology in
2007.

Despite the dramatic difference, the scientists acknowledged that such
observational studies need to be borne out in trials in which
scientists randomly assign patients to one of two groups with
different courses of treatment.

Maria Yazdanbakhsh, an immune-parasitologist at Leiden University in
the Netherlands, and colleagues had done just that in Gabon in
equatorial Africa. To assess whether a parasitic worm infection
protects against allergy, the scientists enlisted 317 schoolchildren,
age 5 to 13, in a study. All of the kids had intestinal parasites,
mainly roundworms, but none had an active allergy to house-dust mites.
Then researchers randomly assigned half the children to get drugs
ridding them of the parasites.

Within a year, 14 percent of the children treated for parasites had
developed a dust mite allergy, skin-prick tests showed, compared with
fewer than 7 percent of those who retained their parasites. The report
appeared in the Journal of Infectious Diseases in 2004.

Some people beset by allergies, asthma or autoimmune disease saw these
early findings and took to stomping around in less-than-sanitary
conditions in Central Africa in hopes of acquiring a parasite to cure
ailments. Anecdotal evidence suggests it can work, but the approach is
unverified and dangerous. Health risks from worm infections can range
from mild (pinworm) to debilitating and sometimes lethal
(schistosomiasis).

Others have resorted to buying unregulated parasite eggs on the
Internet. “It’s available in this underground market, with mixed
results,” says gastroenterologist Jonathan Terdiman of the University
of California, San Francisco. He doesn’t endorse the approach, but he
does regularly see patients with inflammatory bowel disease even if
they are using it. “A lot of these patients are in great need,”
Terdiman says. “The pharmaceutical approach has failed them.”

So controlled clinical trials are needed. To get a treatment trusted
and cleared, scientists need to test it on people randomly assigned to
get the real thing or a placebo. This is the gold standard of medicine
and, unlikely as it might have seemed a decade ago, it’s where
parasitic worm therapy has now arrived.

Cringe-worthy treatment

Joel Weinstock had a perfectly good career as a parasitologist in the
early 1990s when he and Elliott, then colleagues at the University of
Iowa, noticed the lack of autoimmune diseases in the tropics. They
knew about the hygiene hypothesis, which suggests that early exposure
to germs is crucial for normal immune function later on (see “Auto
immunity and the hygiene hypothesis”). And the two knew about the rise
of autoimmunity in the West.

“We asked, ‘What’s missing in developed countries?’ ” Elliott says.
“We still had viruses and bacteria, but we were missing a whole class
— helminths — which used to be universal.” Lab work and tests in
animals soon convinced Elliott and Weinstock that helminth infection
could quell inflammation. By 2000, they were speculating openly that
failure to get parasitic infections might contribute to inflammatory
bowel diseases such as Crohn’s disease or ulcerative colitis.

The researchers found an innocuous gut parasite, the pig whipworm
Trichuris suis, that didn’t cause disease in people. They asked
patients with ulcerative colitis to drink a solution containing either
a placebo or cleaned-up, microscopic T. suis eggs every two weeks for
12 weeks. Roughly half the patients were randomly assigned to receive
each. Of 30 people getting the helminth therapy, 13 improved
substantially, compared with only four of 24 people on the placebo.

Two subsequent studies without placebo comparison groups found that
helminth therapy could benefit people with Crohn’s disease. Of 29 Iowa
volunteers who got T. suis eggs, 21 went into remission. A British-
Australian research team injected hookworm larvae into nine volunteers
who had Crohn’s disease. Most showed improvement, marked by less
intestinal distress.

Despite the promising findings, helminth therapy isn’t a shoo-in. A
placebo-controlled trial in Denmark found no benefit from whipworm
eggs given over three weeks for hay fever, scientists reported in
January 2010 in the Journal of Allergy and Clinical Immunology.
Another trial, at Nottingham, showed that very small doses of hookworm
larvae proved no better than a placebo at controlling symptoms in 32
asthma patients. Those data appeared online in December 2009 in
Clinical & Experimental Allergy.

But those results haven’t dimmed interest in the strategy. At the
University of Wisconsin–Madison, neurologist John Fleming and his
colleagues are testing pig whipworm eggs in MS patients, using what
tastes like a sports drink to deliver the eggs. At Mount Sinai School
of Medicine in New York City, scientists are recruiting participants
to test the treatment against autism, which some people hypothesize
has autoimmune links. In Boston, researchers at Beth Israel Deaconess
Medical Center plan to try it for peanut allergy. A large Crohn’s
disease trial is planned for Europe, Weinstock says, and Denmark will
host an MS trial. For some trials, the German company Ovamed GmbH is
providing live whipworm eggs that are free of bacteria and viruses and
are of uniform size.

Purposely ingesting parasitic larvae or eggs “has an audacity about
it,” says Fleming. “It doesn’t seem like mainstream science at first
pass.”

Not everyone is sold on the approach. “The problem with giving people
helminths is you’re introducing a foreign organism, and that has the
specter of unforeseen consequences,” McKay says. Though the pig
whipworm eggs currently used in clinical trials don’t cause disease in
humans, even the idea is, for some, a bit hard to swallow.

The nitty-gritty

Instead of using live organisms, some scientists propose figuring out
and mimicking what the parasites do to ratchet down inflammation. The
problem is, Fleming says, “Worms know more about the human immune
system than we do.”

To catch up, scientists have delved into the molecular mechanisms by
which parasites tone down aberrant immune reactions, particularly
inflammation. Although inflammation is a normal response to infection
that helps in healing, chronic inflammation can damage healthy tissues
and plays a central role in most allergy, asthma and autoimmunity.

Weinstock, now at Tufts Medical Center in Boston, links parasites’
effects to changes in innate immunity, the first-line, nonspecific
branch of the immune system that reacts against foreign materials or
pathogens (in contrast with adaptive immunity in which the body
generates agents against specific pathogens). Helminth exposure seems
to tilt two innate immune cells, macrophages and dendritic cells, away
from promoting inflammation and toward suppressing it, he says.

McKay and his team have studied the effects of helminth exposure by
inducing colitis in rodents and then knocking out this inflammatory
condition with a tapeworm infection. In response to the infection, the
rodents produce more of the immune messenger protein interleukin-10.
“We’re very convinced that interleukin-10 is an important part of the
anti-inflammatory response driven by worms to block colitis,” he says.

How interleukin-10 got this role is less clear, but McKay thinks it
might function as a corrective mechanism, settling down immunity after
the body has taken its best shot at killing a parasite. “Maybe
interleukin-10 is upregulated to reset the immune system back to
normal after the worm is rejected,” he says.

Other researchers are focusing on anti-inflammatory agents of the
immune system called regulatory T cells, or T-regs. Run-of-the-mill T
cells morph into T-regs when a parasitic infection triggers production
of a protein called Foxp3. Also attracting scientific attention: the
inflammation-stopping protein TGF-beta and the immune protein
interleukin-22.

These cells and proteins could be the active agents knocking back
symptoms in people with autoimmunity who have benefited from helminth
therapy, Elliott says. And they might all be necessary.

“It appears it’s a lot like getting a kid to clean his room,” he says.
“You offer money, turn off the TV, hide the video games — then the
room gets cleaned. Any one thing won’t do it.”

The next step is to find out how the parasites induce the host’s cells
to make these anti-inflammatory agents.

To that end, Haas of Borstel and his team are studying a nasty
helminth called Schistosoma mansoni, which causes schistosomiasis, and
focusing on three compounds in the parasite’s eggs that seem to affect
only the host. “The worm would not take the effort to make compounds
like this, which clearly mediate the interaction with the host immune
system, without this being an advantage for them,” Haas says. Sure
enough, animal studies show that these parasite compounds ratchet down
inflammation.

In Scotland, Rick Maizels and colleagues at the University of
Edinburgh have also focused on helminth-secreted compounds,
particularly one called cystatin. And other studies in animals point
to parasite compounds called glycans. “We’re trying to establish a
hierarchy of strength-of-effect,” says Maizels, among parasites and
the compounds they unleash to modulate the human immune system.

Some scientists wonder whether helminth therapy (or infection) might
even cause permanent changes in immunity.

“Very early imprinting and reprogramming of our immune systems is
exciting and possible,” Yazdanbakhsh says. She cites the hygiene
hypothesis: “It seems to me that early life events are determining
things later.”

Maizels, Haas, McKay and others hope to lay the groundwork for a
therapy that tricks the immune system into toning down inflammation,
just as the parasites do. “Identifying these [parasite] products could
be the blueprints for new drugs,” McKay says.

Yazdanbakhsh predicts the key will be to get precise inflammation-
regulating molecules from the parasites. “I tell my students that we
don’t want another set of nonspecific immune suppressants, like
steroids. We need to be really specific.”

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

Autoimmunity and the hygiene hypothesis

Genetics would seem to account for why some people get autoimmune
diseases and others don’t. To find out, researchers have looked at
identical twins, who share a single set of genes. Sure enough, a
person whose identical twin has an autoimmune disease, allergy or
asthma runs a greater risk than the average person of developing that
same problem. Yet genes alone don’t explain all of the risk. For
example, studies show that having an identical twin with asthma bumps
the other twin’s risk up more than 60 percent. But this “concordance”
rate is less than half in identical twins with type 1 diabetes and
considerably lower in twins with lupus, multiple sclerosis or
rheumatoid arthritis.

Proponents of the hygiene hypothesis argue that while genetics matter,
environmental factors play a key role in most autoimmune disorders,
which surged in developed nations in the late 20th century (graph,
left, shows increases in some diseases from baseline levels in various
European nations). The hygiene hypothesis originated when British
researcher David Strachan noted in 1989 that people with lots of
siblings had less hay fever than those with fewer siblings. The
hypothesis holds that squeaky-clean living and few routine infections
in youth can leave the immune system unchallenged, leading to poor
immune-cell education and aberrant reactions down the road. Plenty of
studies support the theory (SN: 1/29/05, p. 68; 9/7/02, p. 150).

Parasite regulation of immunity emerged as an offshoot of this
hypothesis, but intestinal worms aren’t the only pathogens steering
immune development. A study in Arizona showed that attending day care,
and presumedly exposure to viruses and bacteria, might limit asthma
(SN: 8/26/00, p. 134).

Immune instruction might even start before birth. Bianca Schaub of
University Children’s Hospital in Munich and colleagues compared the
umbilical cord blood of babies born to women who, while pregnant, had
spent time on a farm with those who had spent time only in towns.
Newborns whose moms were on the farm developed more of the anti-
inflammatory immune cells called T-regs than the others did, tilting
the farm-exposed babies away from the chronic inflammation of
autoimmune diseases.

http://www.sciencenews.org/pictures/012911/parasites_sidebargraph.gif

<snip>

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

Did i make a OINT about points or did i lay a wormmy eGG?

===========