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1 1st April 06:41
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Default MERCK'S GARDASIL VACCINE NOT PROVEN SAFE FOR LITTLE GIRLS (gastroenteritis asthma appendicitis headache cancer)

Vienna, Virginia

================================================== ==========================
for immediate release

June 27, 2006

National Vaccine Information Center Criticizes FDA for Fast Tracking

Washington, D.C. - The National Vaccine Information Center (NVIC) is
calling on the CDC's Advisory Committee on Immunization Practices (ACIP) to
just say "no" on June 29 to recommending "universal use" of Merck's Gardasil
vaccine in all pre-adolescent girls. NVIC maintains that Merck's clinical
trials did not prove the human papillomavirus (HPV) vaccine designed to
prevent cervical cancer and genital warts is safe to give to young girls.

"Merck and the FDA have not been completely honest with the people about
the pre-licensure clinical trials," said NVIC president Barbara Loe Fisher.
"Merck's pre and post-licensure marketing strategy has positioned mass use
of this vaccine by pre-****s as a morality play in order to avoid talking
about the flawed science they used to get it licensed. This is not just
about ****agers having ***, it is also about whether Gardasil has been
proven safe and effective for little girls."

The FDA allowed Merck to use a potentially reactive aluminum containing
placebo as a control for most trial participants, rather than a non-reactive
saline solution placebo. A reactive placebo can artificially increase the
appearance of safety of an experimental drug or vaccine in a clinical trial.
Gardasil contains 225 mcg of aluminum and, although aluminum adjuvants have
been used in vaccines for decades, they were never tested for safety in
clinical trials. Merck and the FDA did not disclose how much aluminum was in
the placebo.

Animal and human studies have shown that aluminum adjuvants can cause
brain cell death and that vaccine aluminum adjuvants can allow aluminum to
enter the brain, as well as cause inflammation at the injection site leading
to chronic joint and muscle pain and fatigue. Nearly 90 percent of all
Gardasil recipients and 85 percent of aluminum placebo recipients reported
one or more adverse events within 15 days of vaccination, particularly at
the injection site. Pain and swelling at injection site and fever occurred
in approximately 83 percent of Gardasil and 73 percent of aluminum placebo
recipients. About 60 percent of those who got Gardasil or the aluminum
placebo had systemic adverse events including headache, fever, nausea,
dizziness, vomiting, diarrhea, myalgia. Gardasil recipients had more serious
adverse events such as headache, gastroenteritis, appendicitis, pelvic
inflammatory disease, asthma, bronchospasm and arthritis.

"Merck and the FDA do not reveal in public do***ents exactly how many 9
to 15 year old girls were in the clinical trials, how many of them received
hepatitis B vaccine and Gardasil simultaneously, and how many of them had
serious adverse events after being injected with Gardasil or the aluminum
placebo. For example, if there were fewer than 1,000 little girls actually
injected with three doses of Gardasil, it is important to know how many had
serious adverse events and how long they were followed for chronic health
problems, such as juvenile arthritis."

According to the Merck product manufacturer insert, there was 1 case of
juvenile arthritis, 2 cases of rheumatoid arthritis, 5 cases of arthritis,
and 1 case of reactive arthritis in 11,813 Gardasil recipients plus 1 case
of lupus and 2 cases of arthritis out of 9,701 participants primarily
receiving an aluminum containing placebo. Clinical trial investigators
dismissed most of the 102 Gardasil and placebo associated serious adverse
events, including 17 deaths, that occurred in the clinical trials as

"There is too little long term safety and efficacy data, especially in
young girls, and too little labeling information on contraindications for
the CDC to recommend Gardasil for universal use, which is a signal for
states to mandate it," said Fisher. "Nobody at Merck, the CDC or FDA know if
the injection of Gardasil into all pre-**** girls - especially
simultaneously with hepatitis B vaccine - will make some of them more likely
to develop arthritis or other inflammatory autoimmune and brain disorders as
****agers and adults. With cervical cancer causing about one percent of all
cancer deaths in American women due to routine pap screening, it was
inappropriate for the FDA to fast track Gardasil. It is way too early to
direct all young girls to get three doses of a vaccine that has not been
proven safe or effective in their age group."

The National Vaccine Information Center (NVIC), founded in 1982 by
parents of vaccine injured children, has been a leading critic of
one-size-fits-all mass vaccination policies and the lack of basic science
research into biological mechanisms and high risk factors for
vaccine-induced brain and immune system dysfunction. As a member of the FDA
Vaccines and Related Biological Products Advisory Committee (VRBPAC),
Barbara Loe Fisher urged trials include adequate safety data on
pre-adolescent children and warned against fast tracking Gardasil at the
November 28-29, 2001 VRBPAC meeting
Vaccines & Related Biological

For references and more information, go to
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2 1st April 14:19
bryan heit
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Default MERCK'S GARDASIL VACCINE NOT PROVEN SAFE FOR LITTLE GIRLS (gastroenteritis asthma dialysis appendicitis cancer)

In yet another surprising turn of events, America's largest anti-vaccine
movement has published an article opposing vaccination. Big surprise

This is the most idiotic claim I've ever heard. Anyone who's ever been
involved in a clinical trial, or for that matter, anyone even vaguely
familiar with how science works, knows that the alum-containing placebo
is EXACTLY what you want to use. The whole underlying idea behind the
placebo controls is to give the patient exactly what you're giving to
the people receiving the drug (in this case vaccine) EXCEPT for the
active portion. That way you know any effect you see - be it good or
bad - is due to the active component of the drug, and not due to other
components of the drug. Using saline is the exact opposite of what they
should do - if you're going to use saline as a placebo control then you
may as well not even have controls.

How so? It actually makes it more likely that you'll see detrimental
effects, as you're now injecting yet more things, and therefore are more
likely to see other adverse effects.

Complete and absolute bullshit. In the 50's and 60's there were
literally hundreds of clinical trials which looked at the use of
aluminum compounds as adjuvents, including looking at the safety of
aluminum. Here a couple of examples:

In fact, we know so much about aluminum products as vaccine adjuvents
that they have become the standard, in terms of safety and efficacy,
that we use them as standards by which all new adjuvents are judged:

We've debunked this myth before. The dose and route of administration
of aluminum adjuvents prevents all but a tiny fraction from entering the
brain. In addition, the forms of aluminum which are the most neurotoxic
are not those used in vaccinations:

In fact (and, as we've pointed out before) the only people who
regularily get to toxic levels are people who undergo certain forms of
dialysis, where doses of aluminum thousands of times that used in
vaccines are given:

Oh, and in animal models neurotoxicity is only seen when aluminum is
injected directly into the brain. And for the record, no vaccine is
given via this route:

For that matter, you'll eat more aluminum in a plate of broccoli then
you'll get from a vaccine...

In an unexpected turn of events, poking a hole in the skin caused some
minor problems. GASP, who'd have thunked that? Oh no, my arm is sore,
I've got a degree of fever. And gosh darn it - now I'm not going to die
of cervical cancer. Oh, the infamy!

All of which are better then dieing of cancer, and most of which are
regular side effects of vaccination. I notice that the authors of this
"article" once again are caught in a lie; the cases of gastroenteritis,
appendicitis, pelvic inflammatory disease, asthma, bronchospasm and
arthritis were either pre-existing (i.e. patients had them before the
trial), or occurred at the rate you would expect them to occur in the
general population (i.e. probably not caused by the vaccine).

Phase II trials & follow-ups:

Furthermore, the phase III results are not yet publically available, so
any conclusions based on the partial results available are immature.

That information will be released when the phase-III trial report is
released. You need only look at the phase II data to see that...

Which will be published, as it was for the phase II trials. The FDA
would already have had this info before they made their decision.
Unfortunately, due to the peer-review process, the rest of us will have
to wait another 4-6 months (or more) to see these results. Based on the
pahse-II trials, and the published info on the phase-III, we can expect
the mean age to be ~20 years, +/- 5.

i.e. 0.0085% of patients. This is actually much less then what you
would expect to see in the general population of under-20-year-olds,
where the rate is 10-20 per 100,000 - i.e. 0.01-0.02%.

Same as above, only in adults. And the rates of RA in the general
population is much higher than the rates of JA.

Same as above, although it is difficult to do direct comparisons as we
do not know which forms of arthritis were found.

It's also important to note that reactive arthritis is a genetic
disease, and that only patients with a specific mutation (HLA-B27) will
get it. And they can get it in response to any inflammatory stimuli -
be it an infection, vaccine, sprain, etc. So saying this is a result of
vaccination is an out-an-out lie. It's a result of genes - it just
happens that one person with this gene happened to end up in the trial.
Speaks to the broadness of the trial. Had Merek wanted to make their
vaccine seem as safe as possible they could have eliminated this patient
from the study. But instead they chose to keep them in.

Both of which occurred at a rate similar to what you would expect in the
general population. Lupus has a rate of ~0.01-0.06% in the general
population. 1:9701 = 0.01%, exactly what you would expect if you were
just looking at the same number of people, but not giving them a thing.

Same is true for arthritis, with the caveat mentioned above.

And your proof that the unrelated events were not unrelated is? If they
occur in the trial at the same rate as in the regular population then
you cannot say they were due to the trial. And that is the standard
used - the rates of disease(s) must be higher then that in the
population to say they were caused by the trial.

There is a hell of a lot of work in this area. Just because the
founders of this organization cannot understand it doesn't mean that it

And as a result of her, and other, recommendations the vaccine underwent
another 5 years of testing. Look - the system works!

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3 1st April 14:19
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Default MERCK'S GARDASIL VACCINE NOT PROVEN SAFE FOR LITTLE GIRLS (tetanus meningitis diphtheria pertussis hepatitis)

You vaccine makers have to believe

Vancouver neuroscientist Chris Shaw shows a link between the aluminum
hydroxide used in vaccines, and symptoms associated with Parkinson's,
amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), and Alzheimer's....."This
is suspicious," he told the Ge****a Straight in a phone interview from his
lab near Heather Street and West 12th Avenue. "Either this [link] is known
by industry and it was never made public, or industry was never made to do
these studies by Health Canada. I'm not sure which is scarier." Similar
adjuvants are used in the following vaccines, according to Shaw's paper:
hepatitis A and B, and the Pentacel ****tail, which vaccinates against
diphtheria, pertussis, tetanus, polio, and a type of meningitis...."No one
in my lab wants to get vaccinated," he said. "This totally creeped us out.
We weren't out there to poke holes in vaccines. But all of a sudden, oh my
God-we've got neuron death!"Another important factor with regard to mercury
on the mind, which officials at the CDC, FDA and the professors in the IOM
do not consider, is synergistic toxicity - mercury's enhanced effect when
other poisons are present. A small dose of mercury that kills 1 in 100 rats
and a dose of aluminum that will kill 1 in 100 rats, when combined have a
striking effect: all the rats die. Doses of mercury that have a 1 percent
mortality will have a 100 percent mortality rate if some aluminum is there.
Vaccines contain aluminum.
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4 1st April 14:20
bryan heit
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Posts: 1

There is a possible, but unproven, link between aluminum and some
neurological disorders. But the simple reality is that you eat far more
aluminum every day then there is in a vaccine. For that matter, you'll
get far higher blood levels (about 100x) of aluminum from eating just
one antacid tablet then you will for a vaccine. So worrying about the
aluminum in vaccines is kinda silly - they account for only a few
hundred thousandths the aluminum your body will have to deal with over
your life time. Had you bothered to click on the links I provided you'd
have seen a review of those studies.
It's also worth mentioning that the aluminum -> neurological disease
connection is highly controversial. And the reason is simple - the data
in support of the theory is rather weak.

Not that we should be surprised you ignored all that - you go out of
your way to avoid reality. After all, dealing with reality may actually
require you to use your brain.

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5 1st April 14:20
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Yeah Bryan, f****ve me if I seek an unbiased opinion over yours, you lot
have been using mercury decades after you knew it wasn't safe, and you never
did any safety studies anyway before you put it on the market.

And f****ve me if I think injecting it directly into babies is a bit
different to eating it. Not that I believe your --we eat as much every day
line. Is that for babies on breast milk too?
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6 1st April 14:20
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Default MERCK'S GARDASIL VACCINE NOT PROVEN SAFE FOR LITTLE GIRLS (renal kidney alzheimer virus bacteria)

F****ve me if I can't see much in those links, only one abstract and that
mentions a titre study. cine adjuvents

That was hep b on 18 year olds, not new born babies

And I don't read scientific language normally, so I'd have to get someone
who could to translate it and see if it was bullshit, and seeing as one
estimate put only 1% of peer review papers as scientifically sound the odds
are against this one, then you have to see the source of funding--bound to
be the vaccine companies. Thirdly, titres don't do much for me as they
aren't a measure of immunity

"Human trials generally correlate "antibody" responses with protection -
that is if the body produces antibodies (proteins) which bind to vaccine
components, then it must be working and safe. Yet Dr March says antibody
response is generally a poor measure of protection and no indicator at all
of safety. "Particularly for viral diseases, the 'cellular' immune response
is all important, and antibody levels and protection are totally unconnected."--

Sure, one guy cured his alzheimer's by giving up laxatives, ie antacids I believe

Not directly, but does it matter how long the poison takes to get to your

"The blood-brain barrier is not intact in infants until at least 6 weeks of
life. This is why a newborn with a fever must be subjected to a spinal tap
to rule out menningitis. Any virus or bacteria that a newborn is exposed to
can go directly to the nervous system. This is why the Hepatitis B vaccine
at birth is so dangerous. Between 1991 and 1999, when the shot contained
thimerisol, giving it at birth would have resulted in mercury crossing into
the brain since the blood-brain barrier was not yet intact. As a nurse, I'm
concerned that this information about the normal timing of a blood-brain
barrier forming is not more readily known. I think this normal delay in the
forming of a blood-brain barrier is an important piece of the puzzle and one
of the reasons for the surge of autism in the 90's."----Mary Barbera RN, MSN

And did any of your supposed studies study the synergy between mercury and

"A single vaccine given to a six-pound newborn is the equivalent of giving a
180-pound adult 30 vaccinations on the same day. Include in this the toxic
effects of high levels of aluminum and formaldehyde contained in some
vaccines, and the synergist toxicity could be increased to unknown levels.
Further, it is very well known that infants do not produce significant
levels of bile or have adult renal capacity for several months after birth.
Bilary transport is the major biochemical route by which mercury is removed
from the body, and infants cannot do this very well. They also do not
possess the renal (kidney) capacity to remove aluminum. Additionally,
mercury is a well-known inhibitor of kidney function."--Boyd Haley Ph.D.

Note renal capacity.
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7 1st April 14:20
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Posts: 1

I like this mercury letter, and these extracts especially. Makes me want to
trust waht you say about aluminium, not:

"Thimerosal has been used in vaccines for more than 70 years, but has
never been adequately tested for safety or proven to be safe. The FDA
approved its use by a "grandfather" mechanism that allowed its use
because it was in use before the FDA existed."

"Dr. Kahn's suggestion that multiple studies have demonstrated that
thimerosal in vaccines cause no harm is false. The studies on which Dr.
Kahn presumably relies, population based statistical studies, cannot be
used to disprove an association between thimerosal and
neurodevelopmental disorders, according to Thomas Verstraeten, the
primary CDC author of the principal United States study. Early versions
of the U.S. study, not disclosed to the public but obtained via the
Freedom of Information Act, did show an association between thimerosal
and neurological disorders."

Response to "Don't Ban Thimerosal" by Dr. Laura Kahn in Asbury Park Press
(pasted below) To the Editor: Here is a corrected version of my letter. The earlier version contained some typographical and syntactical errors. ================================================== ======== To the Editor: Dr. Laura H. Kahn's piece. "Don't Ban Thimerosal". is long on opinion but short on facts. Dr. Kahn suggests that legislation limiting the use of thimerosal in vaccines would impose "unnecessary restrictions" on the availability of an "effective" vaccine. She suggests that pending NJ legislation (A-1324) would cause this restriction. This allegation is a complete distortion of the effect of the legislation. Section 1.d. of the NJ bill provides that higher levels of thimerosal in vaccines may be used in the case of a disease outbreak or vaccine shortage. Thus Dr. Kahn is incorrect to claim that the legislation would restrict availability. The greatest past threat to flu vaccine supply, moreover, that occurred in 2004 when Chiron was required to destroy 50 million contaminated doses of flu vaccines, involved thimerosal-containing vaccines. Limiting thimerosal would not have affected this cause of supply shortage, which implicated thimerosal's effectiveness as an anti-bacterial agent in vaccines. In addition, for years there has been an oversupply of flu vaccine, with manufacturers having to destroy unused doses of vaccine at the end of the flu season. Thus, Dr. Kahn's concern that the NJ legislation would affect supply is misplaced, and overlooks much more serious factors that affect flu vaccine supply. Dr. Kahn wrongheadedly calls the New Jersey proposal "anti-immunization legislation." This gross mischaracterization betrays Dr. Kahn's bias as the New Jersey legislation would not in any way restrict immunization. Rather, the legislation would inspire public confidence in vaccines because mercury, universally recognized as a potent neurotoxin, would be reduced in vaccines. Thimerosal has been used in vaccines for more than 70 years, but has never been adequately tested for safety or proven to be safe. The FDA approved its use by a "grandfather" mechanism that allowed its use because it was in use before the FDA existed. Contrary to Dr. Kahn's assertion, vaccine manufacturers such as Sanofi-Pasteur have categorically stated (by Sanofi spokesperson Len Lavenda) that they can manufacture enough doses of thimerosal-reduced vaccine to meet the demand for use in children and pregnant women. In the United States distribution using single dose vials or syringes is, therefore, not an issue. The cost would only be pennies greater than current cost; surely a cost of pennies per dose is worthwhile when the safety of our children is in question. Dr. Kahn's suggestion that multiple studies have demonstrated that thimerosal in vaccines cause no harm is false. The studies on which Dr. Kahn presumably relies, population based statistical studies, cannot be used to disprove an association between thimerosal and neurodevelopmental disorders, according to Thomas Verstraeten, the primary CDC author of the principal United States study. Early versions of the U.S. study, not disclosed to the public but obtained via the Freedom of Information Act, did show an association between thimerosal and neurological disorders. Other studies that vaccine promoters like Dr. Kahn choose to ignore do show an association between thimerosal-containing vaccines and neurodevelopmental disorders. Even the Institute of Medicine's ("IOM") report on this subject could not rule out the possibility that mercury might cause problems in subsets of children, and the authors of that review stated that mercury causes neurological and immune problems. The IOM has reported that the link between thimerosal-containing vaccines and neurodevelopmental disorders is "biologically plausible." No one who supports the limitation of mercury in New Jersey's vaccines suggests that flu vaccines should be banned, as Dr. Kahn misleadingly suggests, What we who are concerned about vaccine safety for our children want is safe and responsible vaccination by elimination or reduction of mercury in solutions that are injected into children and pregnant women. To say, as does Dr. Kahn, that reducing avoidable mercury exposure via vaccines is "bad public health policy" is recklessly irresponsible, when recent studies (Palmer , Windham) clearly show an association between mercury and autism spectrum disorders. In the interest of the health of our children and safe vaccination practice urge your Assembly members to vote yes on A- 1324. Robert J. Krakow, Esq. Parent President, A-CHAMP Advocates for Children's Health Affected by Mercury Poisoning 2001 Marcus Avenue, Suite N125 Lake Success, NY 11042
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8 1st April 20:03
bryan heit
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Posts: 1

And as I've always stated - ask for any article you want and I'll
forward you the PDF. That offer is always open; even for unrelated
articles you may be interested in. Others have taken advantage of this
offer in the past - why haven't you?

And yet you regularly proclaim your expertise in all sorts of scientific
areas! So there you have it - John has claimed here, in front of all,
that he is personally incapable of understanding science!

Given that you've admitted to not understanding science I guess we can
excuse your confusion as to what titers mean, and what we use them as a
measure for. All titer tells you is that your body has responded to the
vaccine in such a manner as to produce antibodies. It's a simple test
which confirms that you're immune system has responded to the vaccine in
an appropriate manner.

This is a gross distortion of the truth. Firstly, antibodies are
essential in anti-viral responses. The neutralize viruses which are
floating around free in the blood and tissues, and can also kill cells
which are infected with the virus.

Secondly, in order to get antibodies produced against anything, aside
from a very small group of special bacterial antigens, you must first
have activation of the cellular immune response - the very immune
response which Dr March points out (correctly) is required for proper
anti-viral responses. You simply do not get antibody responses without
this occurring first. You can read more on this in any immunology text,
or by searching the web for "b-cell activation". Here's a start:

Laxities and antacids are totally different things, made of entirely
different chemicals. Laxities (usually) contain a mix of fiber and
soap-like chemicals which essentially "lube-up" your digestive tract.
Antacids contain a mix of various basic chemicals which work by reacting
with, and thus neutralizing, stomach acid.

Completely different chemicals, completely different mechanism of
action. Not that we're surprised you don't know the huge difference
between the two.

Had you read the links I posted you would have seen that the amount
which reaches the brain is very small, as aluminum is readily cleared by
a variety of routes. So by the time your brain has a chance to absorb
some, most of it has already been expelled.

Yep, we've covered that before in the mercury papers. The issue of
potential synergy was well covered by those studies.

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9 1st April 20:03
bryan heit
External User
Posts: 1

Why trust me? I provided you the links, to papers which looked directly
at the safety of aluminum. Once again proving that you have your
beliefs, and will ignore anything which counters them, rather then
dealing with reality. I notice you conveniently cropped them from your reply...

And since then it has been scrutinized extensively for safety, both
through correlation studies and experimental studies. I've linked you
to over 25 papers on this subject in past messages. Rather than
repeating myself here I'll direct you to google groups where you can
search for the relevant posts.

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10 1st April 20:04
jan drew
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Default MERCK'S GARDASIL VACCINE NOT PROVEN SAFE FOR LITTLE GIRLS (dementia renal tetanus calcium diphtheria)

Safety of Aluminum Added to Vaccines as a Vaccine Adjuvant

E-mail from Dr. Philip Rudnick Ph.D.
Professor Emeritus, Chemistry
West Chester University of Pennsylvania

Date: Sun, 08 Dec 2002 15:08:06 -0500
Subject: Aluminum Neurotoxicity


Thimerosal is certainly a very potent neurotoxin. It should never have
been used in vaccines, particularly for infants and children. But what about
aluminum INJECTED into the body not as a vaccine preservative but as a
vaccine adjuvant? (Aluminum is not readily absorbed from the GI tract.)
Aluminum, also is a neurotoxin. This has been known for over 100 years. And
what safety studies have ever been done about the possible neurotoxic
interaction/synergism of thimerosal and aluminum?


Philip Rudnick, PhD

Professor Emeritus, Chemistry

West Chester University of Pennsylvania

Some Refences:

Redhead K, Quinlan GJ, Das RG, Gutteridge JM. Pharmacol Toxicol 1992

Aluminium-adjuvanted vaccines transiently increase aluminium levels in
murine brain tissue.

Division of Bacteriology, National Institute for Biological Standards
and Control, Herts., UK.

Aluminum is widely used as an adjuvant in human vaccines, and children
can often receive up to 3.75 mg of parenteral aluminum during the first six
months of life. We show that int****ritoneal injection of aluminum adsorbed
vaccines into mice causes a transient rise in brain tissue aluminum levels
peaking around the second and third day after injection. This rise is not
seen in the saline control group of animals or with vaccine not containing
aluminum. It is likely that aluminum is transported to the brain by the
iron-binding protein transferrin and enters the brain via specific
transferrin receptors. PMID: 1608913, UI: 92302160

Gupta RK, Relyveld EH.

Adverse reactions after injection of adsorbed
diphtheria-pertussis-tetanus (DPT) vaccine are not due only to pertussis
organisms or pertussis components in the vaccine.

Vaccine. 1991 Oct;9(10):699-702. Review.PMID: 1759487; UI: 92101590

Aluminum compounds such as aluminum phosphate and aluminum hydroxide
are the most commonly used adjuvants with vaccines for human use. Due to the
increasing concern about the toxicity of aluminum, other adjuvants like
calcium phosphate may be evaluated as an alternative to aluminum adjuvants.
To minimize reactions after immunization with DPT vaccine due to impurities
in the toxoids, the use of toxoided purified toxins is suggested.

Neurotoxicology of the brain barrier system: new implications.

Zheng W.

J Toxicol Clin Toxicol. 2001;39(7):711-9.

College of Physicians and Surgeons, Columbia University, New York, New
York 10032, USA.

The concept of a barrier system in the brain has existed for nearly a
century. The barrier that separates the blood from the cerebral interstitial
fluid is defined as the blood-brain barrier, while the one that discontinues
the circulation between the blood and cerebrospinal fluid is named the
blood-cerebrospinal fluid barrier. Evidence in the past decades suggests
that brain barriers are subject to toxic insults from neurotoxic chemicals
circulating in blood. The aging process and some disease states render
barriers more vulnerable to insults arising inside and outside the barriers.
The implication of brain barriers in certain neurodegenerative diseases is
compelling, although the contribution of chemical-induced barrier
dysfunction in the etiology of any of these disorders remains poorly
understood. This review examines what is currently understood about brain
barrier systems in central nervous system disorders by focusing on
chemical-induced neurotoxicities including those associated with
nitrobenzenes, N-methyl-D-aspartate, cyclosporin A, pyridostigmine bromide,
aluminum, lead, manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and
3-nitropropionic acid. Contemporary research questions arising from this
growing understanding show enormous promises for brain researchers,
toxicologists, and clinicians.

Aluminum, NO, and nerve growth factor neurotoxicity in cholinergic

Szutowicz A.

J Neurosci Res. 2001 Dec 1;66(5):1009-18.

Chair of Clinical Biochemistry, Department of Laboratory Medicine,
Medical University of Gda┼"sk, Debinki 7, 80-211 Gda┼"sk, Poland.

Several neurotoxic compounds, including Al, NO, and beta-amyloid may
contribute to the impairment or loss of brain cholinergic neurons in the
course of various neurodegenerative diseases. Genotype and phenotypic
modifications of cholinergic neurons may determine their variable functional
competency and susceptibility to reported neurotoxic insults. Hybrid,
immortalized SN56 cholinergic cells from mouse septum may serve as a model
for in vitro cholinotoxicity studies. Differentiation by various
combinations of cAMP, retinoic acid, and nerve growth factor may provide
cells of different morphologic maturity as well as activities of
acetylcholine and acetyl-CoA metabolism. In general, differentiated cells
appear to be more susceptible to neurotoxic signals than the
non-differentiated ones, as evidenced by loss of sprouting and connectivity,
decreases in choline acetyltransferase and pyruvate dehydrogenase
activities, disturbances in acetyl-CoA compartmentation and metabolism,
insufficient or excessive acetylcholine release, as well as increased
expression of apoptosis markers. Each neurotoxin impaired both acetylcholine
and acetyl-CoA metabolism of these cells. Activation of p75 or trkA
receptors made either acetyl-CoA or cholinergic metabolism more susceptible
to neurotoxic influences, respectively. Neurotoxins aggravated detrimental
effects of each other, particularly in differentiated cells. Thus brain
cholinergic neurons might display a differential susceptibility to Al and
other neurotoxins depending on their genotype or phenotype-dependent
variability of the cholinergic and acetyl-CoA metabolism.

Copyright 2001 Wiley-Liss, Inc.

Aluminium impairs the glutamate-nitric oxide-cGMP pathway in cultured
neurons and in rat brain in vivo: molecular mechanisms and implications for

C****es JJ, Corbalan R, Montoliu C, Llansola M, Monfort P, Erceg S,
Hernandez-Viadel M, Felipo V.

J Inorg Biochem. 2001 Nov;87(1-2):63-9.

Laboratory of Neurobiology, Instituto de Investigaciones Citol├│gicas,
Fundaci├│n Valenciana de Investigaciones Biom├ędicas, Amadeo de Saboya 4,
46010 Valencia, Spain.

Aluminium (Al) is a neurotoxicant and appears as a possible
etiological factor in Alzheimer's disease and other neurological disorders.
The mechanisms of Al neurotoxicity are presently unclear but evidence has
emerged suggesting that Al ac***ulation in the brain can alter neuronal
signal transduction pathways associated with glutamate receptors. In
cerebellar neurons in culture, long term-exposure to Al added 'in vitro'
impaired the glutamate-nitric oxide (NO)-cyclic GMP (cGMP) pathway, reducing
glutamate-induced activation of NO synthase and NO-induced activation of the
cGMP generating enzyme, guanylate cyclase. Prenatal exposure to Al also
affected strongly the function of the glutamate-NO-cGMP pathway. In cultured
neurons from rats prenatally exposed to Al, we found reduced content of NO
synthase and of guanylate cyclase, and a dramatic decrease in the ability of
glutamate to increase cGMP formation. Activation of the glutamate-NO-cGMP
pathway was also strongly impaired in cerebellum of rats chronically treated
with Al, as assessed by in vivo brain microdialysis in freely moving rats.
These findings suggest that the impairment of the Glu-NO-cGMP pathway in the
brain may be responsible for some of the neurological alterations induced by

Effects of aluminium exposure on brain glutamate and GABA systems: an
experimental study in rats.

Nayak P, Chatterjee AK.

Food Chem Toxicol. 2001 Dec;39(12):1285-9.

Biochemistry and Nutrition Research Laboratory, Department of
Physiology, University of Calcutta, 92 A.P.C. Road, 700 009, Calcutta,

It has been postulated that the neurotoxic effects of aluminium could
be mediated through glutamate, an excitatory amino acid. Hence the effects
of aluminium administration (at a dose of 4.2mg/kg body weight daily as
aluminium chloride, hexahydrate, int****ritoneally, for 4 weeks) on
glutamate and gamma-amino butyrate (GABA), an inhibitory amino acid, and
related enzyme activities in different regions of the brain were studied in
albino rats. The glutamate level increased significantly in the cerebrum,
thalamic area, midbrain-hippocampal region and cerebellum in response to in
vivo aluminium exposure. The aluminium insult also caused significant
increases in glutamate alpha-decarboxylase activity in all the brain
regions. However, on aluminium insult, the GABA content was not
significantly changed except in the thalamic area, where it was elevated. On
the contrary, the GABA-T activities of all the regions were reduced
significantly in all regions except the midbrain-hippocampal region.
However, the succinic semi-aldehyde content of all brain regions increased,
often significantly. The aluminium-induced modification of the enzyme
activities may be either due to the direct impact of aluminium or due to
aluminium-induced changes in the cellular environment. The aluminium-induced
differential regional ac***ulation of glutamate or other alterations in
enzymes of the glutamate-GABA system may be one of the causes of
aluminium-induced neurotoxicity.

Dementia in patients undergoing long-term dialysis: aetiology,
differential diagnoses, epidemiology and management.

Rob PM, Niederstadt C, Reusche E.

CNS Drugs. 2001;15(9):691-9.

Nephrologisches Zentrum am Klinikum S├╝d, Kalhlhorststrasse 31,
D-23552 L├╝beck, Germany.

Dementia in patients undergoing long-term dialysis has not been
clearly defined; however, four different entities have been described.
Uraemic encephalopathy is a complication of uraemia and responds well to
dialysis. Dialysis encephalopathy syndrome, the result of acute intoxication
of aluminium caused by the use of an aluminium-containing dialysate, was a
common occurrence prior to 1980. However, using modern techniques of water
purification, such acute intoxication can now be avoided.
Dialysis-associated encephalopathy/dementia (DAE) is always associated with
elevated serum aluminium levels. Pathognomonic morphological changes in the
brain have been described, but the mechanism for the entry of aluminium into
the CNS is incompletely understood. The mechanisms involved in the
pathogenesis of the neurotoxicity associated with aluminium are numerous.
Although only a very small fraction of ingested aluminium is absorbed, the
continuous oral aluminium intake from aluminium-based phosphate binders, and
also of dietary or environmental origin, is responsible for aluminium
overload in dialysis patients. Age-related dementia, especially vascular
dementia, occurs in patients undergoing long-term dialysis as frequently as
it does in the general population. The differential diagnoses of
dialysis-associated dementias should include investigation for metabolic
encephalopathies, heavy metal or trace element intoxications, and distinct
structural neurological lesions such as subdural haematoma, normal pressure
hydrocephalus, stroke and, particularly, hypertensive encephalopathy and
multi-infarct dementia. To prevent DAE, dietary training programmes should
aim to achieve the lowest phosphate intake and pharmacological tools should
be used to keep serum phosphate levels below 2 mmol/L. To prevent vascular
dementia, lifestyle modification should be undertaken, including optimal
physical activity and fat intake, nicotine abstinence, and targeting optimal
blood glucose, cholesterol and triglyceride levels, and blood pressure, to
those outlined in current recommendations.

The toxicology of aluminum in the brain: a review.

Yokel RA.

Neurotoxicology. 2000 Oct;21(5):813-28.

College of Pharmacy and Graduate Center for Toxicology, University of
Kentucky Medical Center, Lexington, USA.

Aluminum is environmentally ubiquitous, providing human exposure.
Usual human exposure is primarily dietary. The potential for significant Al
absorption from the nasal cavity and direct distribution into the brain
should be further investigated. Decreased renal function increases human
risk of Al-induced ac***ulation and toxicity. Brain Al entry from blood may
involve transferrin-receptor mediated endocytosis and a more rapid process
transporting small molecular weight Al species. There appears to be Al
efflux from the brain, probably as Al citrate. There is prolonged retention
of a fraction of Al that enters the brain, suggesting the potential for
ac***ulation with repeated exposure. Al is a neurotoxicant in animals and
humans. It has been implicated in the etiology of sporadic Alzheimer's
disease (AD) and other neurodegenerative disorders, although this is highly
controversial. This controversy has not been resolved by epidemiological
studies, as only some found a small association between increased incidence
of dementia and drinking water Al concentration. Studies of brain Al in AD
have not produced consistent findings and have not resolved the controversy.
Injections of Al to animals produce behavioral, neuropathological and
neurochemical changes that partially model AD. Aluminum has the ability to
produce neurotoxicity by many mechanisms. Excess, insoluble amyloid beta
protein (A beta) contributes to AD. Aluminum promotes formation and
ac***ulation of insoluble A beta and hyperphosphorylated tau. To some
extent, Al mimics the deficit of cortical cholinergic neurotransmission seen
in AD. Al increases Fe-induced oxidative injury. The toxicity of Al to
plants, aquatic life and humans may share common mechanisms, including
disruption of the inositol phosphate system and Ca regulation. Facilitation
of Fe-induced oxidative injury and disruption of basic cell processes may
mediate primary molecular mechanisms of Al-induced neurotoxicity. Avoidance
of Al exposure, when practical, seems prudent.

Aluminum neurotoxicity in preterm infants receiving
intravenous-feeding solutions.

Bishop NJ, Morley R, Day JP, Lucas A.

N Engl J Med. 1997 May 29;336(22):1557-61.

Comment in:

N Engl J Med. 1997 Oct 9;337(15):1090-1 PMID: 9324646

Medical Research Council (MRC) Dunn Nutrition Unit, Cambridge, United

BACKGROUND: Aluminum, a contaminant of commercial intravenous-feeding
solutions, is potentially neurotoxic. We investigated the effect of
perinatal exposure to intravenous aluminum on the neurologic development of
infants born prematurely. METHODS: We randomly assigned 227 premature
infants with gestational ages of less than 34 weeks and birth weights of
less than 1850 g who required intravenous feeding before they could begin
enteral feeding to receive either standard or specially constituted,
aluminum-depleted intravenous-feeding solutions. The neurologic development
of the 182 surviving infants who could be tested was assessed by using the
Bayley Scales of Infant Development at 18 months of age. RESULTS: The 90
infants who received the standard feeding solutions had a mean (+/-SD)
Bayley Mental Development Index of 95+/-22, as compared with 98+/-20 for the
92 infants who received the aluminum-depleted solutions (P=0.39). In a
planned subgroup ****ysis of infants in whom the duration of intravenous
feeding exceeded the median and who did not have neuromotor impairment, the
mean values for the Bayley Mental Development Index for the 39 infants who
received the standard solutions and the 41 infants who received the
aluminum-depleted solutions were 92+/-20 and 102+/-17, respectively
(P=0.02). The former were significantly more likely (39 percent, vs. 17
percent of the latter group; P=0.03) to have a Mental Development Index of
less than 85, increasing their risk of subsequent educational problems. For
all 157 infants without neuromotor impairment, increasing aluminum exposure
was associated with a reduction in the Mental Development Index (P=0.03),
with an adjusted loss of one point per day of intravenous feeding for
infants receiving the standard solutions. CONCLUSIONS: In preterm infants,
prolonged intravenous feeding with solutions containing aluminum is
associated with impaired neurologic development.
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