Death of Alzheimer victim linked to aluminium pollution Brain autopsy of pollution victim...

news@nature.com ^ | 21 April 2006 | Michael Hopkin

[neverdem]

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Published online: 21 April 2006; | doi:10.1038/news060417-10

Death of Alzheimer victim linked to aluminium pollution

Brain autopsy of pollution victim rekindles contaminant fears.

Michael Hopkin

Aluminum can accumulate in the twists of deformed proteins that characterize Alzheimer's disease.© SPL

Fears of a link between aluminium and Alzheimer's disease have been reignited by the case of a British woman who died of the illness 16 years after an industrial accident polluted her local drinking water.

An autopsy on Carole Cross's brain showed that she was suffering from a rare form of early-onset Alzheimer's when she died in May 2004, and also revealed the presence of high levels of aluminium in her tissues. The researchers who investigated her brain cannot say whether the aluminium was the cause, but point out that the woman had no family history of dementia.

The polluting incident occurred in 1988 when a truck driver mistakenly emptied some 20 tonnes of aluminium sulphate — used in the early stages of wastewater treatment — into a tank containing drinking water destined for the village of Camelford in Cornwall, UK. An estimated 20,000 people may have been exposed to high levels of the chemical for several weeks.

Concerned residents are waiting to see whether more people will be similarly affected. Anecdotal reports state that several other villagers are suffering from dementia.

Something in the water

Although only a single case, the discovery has reopened the possibility that aluminium could be linked to Alzheimer's disease, say Christopher Exley, a chemist at Keele University, UK and Margaret Esiri, a University of Oxford neurologist, who publish details of their investigation on Cross in the Journal of Neurology, Neurosurgery and Psychiatry¹.

Aluminium is firmly linked to some temporary forms of dementia, Esiri says. Kidney dialysis patients living in areas where water is high in aluminium, for example, sometimes experience 'dialysis dementia', as a result of the large quantities of contaminated water passing through their bodies.

But the link between aluminium and Alzheimer's has been more controversial, says Daniel Perl, a neuropathologist at Mount Sinai School of Medicine in New York, who has written a commentary on the Camelford case².

Once aluminium binds to proteins, it sticks for good. It's like trying to use superglue to mend a Swiss watch.  Daniel Perl, Mount Sinai School of Medicine, New York

Aluminium is often found in the twists of deformed protein, called 'neurofibrillary tangles', that characterize the disease. But there is no strong evidence that it is involved in the disease's onset, Perl cautions. "I realize that's quite a conservative answer," he says. "But show me a couple more cases like this and I might have to change it."

Perl points out that, of the 20 most common elements on Earth, aluminium is the only one not involved in any essential biological process. That's because of its feisty chemistry, he explains. When in solution, aluminium ions are small and highly charged, making them very reactive. "Once aluminium binds to proteins, it sticks for good," he says. "It's like trying to use superglue to mend a Swiss watch."

Accelerated illness

What makes Cross's case interesting is that she had succumbed to a very rare form of Alzheimer's, but had a genetic predisposition, through a gene called APOE, to developing a more common form of the disease later in life, says Esiri. This raises the possibility that her aluminium exposure may have accelerated the onset of disease. Previous studies of transgenic mice expressing a similar gene have shown that feeding them aluminium in drinking water can cause similar symptoms at a young age.

Cross's protein tangles were found in the blood vessels rather than in the brain tissue itself. This is consistent with the idea that the cause of the disease could have originated in the gut, reaching the brain through the bloodstream, Esiri explains.

Combined with the unusually young age at which she died (aged 58), this puts her in a category shared by only a handful of known cases worldwide, Esiri says.

The discovery may also rekindle fears over drinking and cooking using aluminium pots and pans, although Perl says that most aluminium is found in an insoluble form and therefore not dangerous. The only way to ingest aluminium would be by cooking acidic foods such as rhubarb or tomato, which would react with the metal.

The news is worrying for Camelford's residents, says Exley, who carried out the chemical analysis to spot the aluminium in the autopsy samples. "There are still 20,000 people thinking about whether they're susceptible to this chronic disease," he says. "We can't do anything to help them."

Visit our newsblog to read and post comments about this story.

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References

1. Exley C.&

   Esiri M. M . J. Neurol. Neurosurg. Psychiatry , doi:10.1136/jnnp.2005.086553(2006).

2. Perl D. P., et al. J. Neurol. Neurosurg. Psychiatry, doi:10.1136/jnnp.2006.090613 (2006).

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[neverdem]

Firm seeks crackdown on custom made drugs

Calif. Stem Cell Agency Still in Limbo - CIRM all politics, no science

Stem Cell Study for Patients with Heart Attack Damage Seeks to Regenerate Heart Muscle

Stem Cell Innovations Produces Human Stem Cells; for Use in Government Funded Laboratories

FReepmail me if you want on or off my health and science ping list.

[neverdem]

Some stem cell links in comment# 2 might interest you.

[MedicalMess]

My bet is on Clostridium difficile as the cause because the use of antibiotics affects the progression of the disease and aluminum does not cause amyloid plaques or inflammation which C. difficile does. Diabetics progress to Alzheimer's and C. difficile shuts down the signaling cascade that trips the release of insulin from the pancreas.

---

Title: IDSA: Antibiotics May Temporarily Stave Off Alzheimer's Disease Symptoms



"IDSA: Antibiotics May Temporarily Stave Off Alzheimer's Disease Symptoms"


By Maury M. Breecher, PhD, MPH SAN DIEGO, CA -- October 15, 2003 -- Results from a small multi-center trial suggest that two common antibiotics taken together might delay the symptoms of Alzheimer's disease (AD), said researchers here October 12th at the 41st Annual Infectious Diseases Society of America (IDSA) Meeting. The antibiotics doxycycline and rifampin may have a therapeutic role in temporarily slowing the progression of Alzheimer's disease symptoms, but the mechanisms of that action remain to be elucidated, according to lead author Mark B. Loeb, MD, MSc, associate professor, departments of pathology and molecular medicine, and clinical epidemiology and biostatistics, McMaster University, Hamilton, Ontario, Canada. In the study, people with AD who took the antibiotics had significantly reduced decline in mental function for at least 6 months compared to those given the placebo, said Dr. Loeb. Most people in the study had been treated with other drugs, and "were not doing very well." "Does this mean you should ask that mom or dad be put on an antibiotic regimen if they have Alzheimer's?" he continued. "If everything else has failed, it's a possibility and something to talk to the physician about, although antibiotic resistance issues should be considered" Other experts consulted at the meeting think that recommendation is premature and point out that the beneficial effects might be as a result of the anti-inflammatory effects of the antibiotics, not their antibacterial actions. "This was a well-designed, preliminary study with clearly interesting findings, but we need to replicate the findings and determine the underlying mechanism involved," said Christopher L. Karp, MD, professor of paediatrics and director of molecular biology, University of Cincinnati Children's Hospital, Cincinnati, Ohio, United States. Dr. Karp was vice chair of the IDSA program committee. "The hypothesis going in to this research was that there are potentially bacteria that are involved in exacerbating Alzheimer's," continued Dr. Karp. "I think it is even more likely that it is the anti-inflammatory effects of doxycycline that they are seeing." Dr. Karp pointed out that there is "very good data in the literature that doxycycline has anti-inflammatory activity. "We know that Alzheimer's disease is associated with a chronic low-grade, local inflammatory response," he explained. "If I were to bet, I would think that the most likely mechanism of action here is inhibition of inflammation." Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate Alzheimer's Disease, but the beneficial mechanism "is unlikely" to be due to the antibacterial effects of those agents, said Dr. Loeb and his colleagues in their presentation. He suggested that the antibiotics might work by interfering with the accumulation of protein plaques around the neurons in the brain, a process that is known to be associated with AD. In a news release prepared by the IDSA, Dr. Loeb and his colleagues stated that prolonged exposure to rifampin and doxycycline could contribute to development of antimicrobial-resistant bacteria, which is "an important potential limitation of the therapy." The study by Dr. Loeb and colleagues was carried out at three Canadian tertiary care facilities and two community geriatric clinics. The study included 101 people with suspected mild to moderate AD. In the study, 50 patients received placebo pills, and 51 were assigned to take two 100-mg tablets of doxycycline and one 300-mg tablet of rifampin daily for 3 months. The study was triple-blinded, so the patient, the treating physicians and the study investigators were not aware who was receiving the antibiotics or the placebos. The size of the study is comparable to that of other interventions tested for the treatment of AD, said Dr. Loeb. A standard Alzheimer's disease test was given to the patients to determine mental function before the study began. Six months later, the test was re-administered to 43 people in the antibiotic group and 39 people in the placebo group (the remainder had dropped out, died or otherwise did not complete the study). Over the 6-month period, The mental scores in the placebo group declined significantly by an average of 2.75 points more, on a 70-point scale, than those who received the antibiotic. At 12 months, there was still a difference between the two groups, although that difference was not considered to be statistically significant. Standard Alzheimer's tests typically show a steady downward slope in mental function during a period of months, and patients on antibiotics showed a reduction in that slope, said Dr. Loeb. Based on the results of the study, 3 months might be an appropriate period to try the antibiotic regimen, he said. Further study might reveal the most appropriate duration of treatment, he said. "The study certainly does need follow-up studies, because I consider most of the data presented here to be science fiction and of little promise," disagreed Margaret R. Hammerschlag, MD, professor of paediatrics and medicine, State University of New York Downstate Medical Center, New York. "The so-called reduction in cognitive decline was no greater than what has been found in studies of placebos. Whatever improvement that was found could be attributed to the anti-inflammation benefits of the antibiotics," said Dr. Hammerschlag. In the news release put out by IDSA, Dr. Loeb said the Canadian study was undertaken because of an existing theory that suggested that the bacterium Chlamydia pneumoniae might play a role in the development of AD and because doxycycline and rifampin are very effective against this bacterium, according to Dr. Loeb. Dr. Hammerschlag pointed out that the study authors themselves found no evidence that levels of C. pneumoniae were reduced significantly, as would be expected if the slowing of cognitive decline in the patients was due to that factor. That's why Dr. Loeb and his colleagues stated in their conclusion that the antibiotic mechanism "is unlikely" to have caused the patients' improvement. The only medications approved for the treatment of AD by the U.S. Food and Drug Administration and Canadian Health Protection Branch are cholinesterase inhibitors, which are designed to preserve brain chemicals important for memory. About half of people who take these medications experience modest improvement, according to the Alzheimer's Association. Most of the patients in the Canadian study were taking cholinesterase inhibitors when the trial began. Co-authors of the paper are William Molloy, Marek Smieja, Tim Standish, Charles Goldsmith, Jim Mahony, Stephanie Smith, Martin O'Donnell, Max Chernesky, Michael Borrie, Earl Decoteau, Warren Davidson, Allan McDougall and Judy Gnarpe. [Study title: A Randomized Controlled Trial of Doxycycline and Rifampin for Patients with Alzheimer Disease. Abstract 516]

[Myrddin]

The possible link between Alzheimer's and aluminum was made almost 35 years ago. It was about that point in my life when underarm deodorant became a part of my daily hygiene. I noticed that my dad used RightGuard anti-perspirant spray with aluminum chlorhydrate. It struck me as kind of stupid to spray an aluminum compound into the air where it could contact the nasal membranes and have a pretty direct shot at the brain.

Fast forward to December 2003. My dad passed on. He had been showing signs of Alzheimer's or Parkinson's for a couple years. His gait shifted to shuffling. His penchant for balancing the checkbook and income to the penny every month gave way to forgetting to pay critical bills. He became agitated and mean for no reason, yet would be unaware of his uncivil behavior some time later. He "lost" his eyeglasses in the trashcan. Is there a connection? There is no history of any senile dementia on either side of his family. Most live to ages 80 to 105. He passed at 73.

[Dont Mention the War]

The researchers who investigated her brain cannot say whether the aluminium was the cause...

Bury that lead!!!

[radiohead]

Diabetics progress to Alzheimer's

Can you explain to this diabetic what you mean?

[Myrddin]

My dad was also diabetic and dependent on daily insulin injections. His daily breakfast was an awful pile of carbohydrates...a bowl of fruit, cranberry juice, donuts, chocolate candies, coffee. I warned him that the daily carbohydrate bomb was going to steal his eyesight. It did.

It seems C. difficile is a problem in hospitals. Clostridia are strict anaerobes. Under stress, then produce a spore to protect the genetic material. Certain hospital cleaning agents that don't contain bleach can stress C. difficle into active sporulation. That actually increases the probability that it will survive to contaminate food and make it back into the digestive tract of a patient. The usual victims are elderly people who develop severe diarrhea.

[Domestic Church]

"Other experts consulted at the meeting think that recommendation is premature and point out that the beneficial effects might be as a result of the anti-inflammatory effects of the antibiotics, not their antibacterial actions."

Has NSAID testing ever been done on alzheimer patients?

[Myrddin]

Yes. See Selected NSAIDs decrease Alzheimer’s plaque-forming protein without adverse effects of anti-inflammatory drugs

[SuziQ]

It may not have only been the aluminum chlorhydrate in anti-perpspirants. When our parents were growing up, in the Depression years, cookware was made of aluminum. I wouldn't be surprised if some of it didn't leach into the foods. We had aluminum cookware for a short time when we were little, but Mom switched to stainless steel cookware as soon as it became available.

It will be curious to see if the levels of adults with Alzheimer's begins to decline corresponding to the time at which most folks began using stainless instead of aluminum cookware.

[MedicalMess]

Diabetic induced dementia is well established. Both diabetes and Alzheimer's disease are amyloid deposit diseases. C. difficile produces two toxins that are neurotoxic and denature proteins. The slush of calcium, white blood cells, imploded cell membranes and congealed proteins forms an amyloid plaque. The infection rate of C. difficile at problematic levels exceeds 50% of the population over 80 years of age. The peripheral neuropathy that you get with diabetes is caused by these two toxins A and B. Toxin A numbs the nerves. Toxin B causes the irritation and pain. With the correct toxin blocking compound or correct combination of antibiotics you can reverse the elevated glucose levels and the peripheral neuropathy. As a example, we reversed my mother's peripheral neuropathy from her knees back down to below her ankles in just 5 days. That is a reversal rate of up to 3 inches a day. We dropped her Humulin use from 40 units down to 10 units a day in the same five-day period. Basically you could call this a miracle, but, it was just hard core scientific research and experimentation.

This bug will inflame and breakdown the arteries, cause blood clots, weakens muscles, destroys the kidneys and does about another 100 things that I don't have the space here to discuss. I will leave you with a document or two which you should copy so that you will know your doctors are scum.

Pay particular attention the the line that starts with the word "However", in the first document. In the second document you should know that Antibiotic induced diarrhea is caused by C. difficile. Also notice many of the associated diseases to diabetes are listed. It is no accident that when you treat for C. difficile you also treat all these known associated autoimmune disorders including diabetes.


Mastoparan-Induced Insulin Secretion from Insulin-Secreting ßTC3 and INS-1 Cells: Evidence for Its Regulation by Rho Subfamily of G Proteins Rajesh H. Amin, Hai-Qing Chen, Rajakrishnan Veluthakal, Robert B. Silver, Jingsong Li, GuoDong Li and Anjaneyulu Kowluru Departments of Pharmaceutical Sciences (R.H.A., H.-Q.C., R.V., A.K.) and Pharmacology (R.B.S.), Physiology, Radiology, and Biomedical Engineering, Wayne State University, and ß Cell Biochemistry Research Laboratory (R.H.A., H.-Q.C., A.K.), John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan 48201; and John D. Dingell Veterans Affairs Medical Center and Argonne National Laboratory (R.B.S.), and Cardiovascular Research Institute (J.L., G.L.), National University Medical Institutes, National University of Singapore, Singapore 117597

Address all correspondence and requests for reprints to: Anjan Kowluru, Ph.D., Department of Pharmaceutical Sciences, College of Pharmacy and Health Professions, Wayne State University, 259 Mack Avenue, Detroit, Michigan 48201. E-mail: akowluru@med.wayne.edu.

Mastoparan, a tetradecapeptide from wasp venom, stimulates insulin secretion from the islet ß-cells, presumably via activation of trimeric G proteins. Herein, we used Clostridial toxins, which selectively modify and inactivate the Rho subfamily of G proteins, to examine whether mastoparan-induced insulin secretion also involves activation of these signaling proteins. Mastoparan, but not mastoparan 17 (an inactive analog of mastoparan), significantly stimulated insulin secretion from ßTC3 and INS-1 cells. Preincubation of ßTC3 cells with either Clostridium difficille toxin B, which inactivates Rho, Cdc42, and Rac, or Clostridium sordellii toxin, which inactivates Ras, Rap, and Rac, markedly attenuated the mastoparan-induced insulin secretion, implicating Rac in this phenomenon. Mastoparan-stimulated insulin secretion was resistant to GGTI-2147, a specific inhibitor of geranylgeranylation of Rho G proteins (e.g. Rac), suggesting that mastoparan induces direct activation of Rac via GTP/GDP exchange. This was confirmed by a pull-down assay that quantifies the binding of activated (i.e. GTP-bound) Rac to p21-activated kinase. However, glucose-induced insulin secretion from these cells was abolished by toxin B or GGTI-2147, suggesting that the geranylgeranylation step is critical for glucose-stimulated secretion. Mastoparan significantly increased the translocation of cytosolic Rac and Cdc42 to the membrane fraction. Confocal light microscopy revealed a substantial degree of colocalization of Rac (and, to a lesser degree, Cdc42) with insulin in ß-cells exposed to mastoparan. Further, stable expression of a dominant negative (N17Rac) form of Rac into INS-1 cells resulted in a significant reduction in mastoparan-stimulated insulin secretion from these cells. Taken together, our findings implicate Rho G proteins, specifically Rac, in mastoparan-induced insulin release.


U.S. Class 424/78.04
Patent Number 5948402
Issue Date 1999 09 07
Assignee Genetics Institute, Inc. Inventor(s) Keith, James Schendel, Paul Title

Method of using IL-11 for treating antibiotic induced diarrhea

Abstract Provided by the present invention are methods of treating a variety of disorders including AIDS, arthritis (rheumatoid arthritis, osteoarthritis, spondyloarthropathies), antibiotic induced diarrheal diseases (Clostridium difficile), multiple sclerosis, osteoporosis, gingivitis, peptic ulcer disease, esophagitis, diabetes, retinitis, uveitis, reperfusion injury after myocardial infarction (MI) or cerebral vascular accident (CVA), aphthous ulcers (oral), atherosclerosis (plaque rupture), prevention of tumor metastases, asthma, preeclampsia, and allergic disorders such as rhinitis, conjunctivitis, and urticaria.

Exmp. Claim 1

Ex Claim text A method of treating an antibiotic induced diarrheal disease, comprising administering a pharmaceutically effective amount of IL-11.

[MedicalMess]

Further, C. difficile toxins are highly cytotoxic. They induce inflammation which has recently been discovered in Alzheimer patients. C. difficile also produces amyloid plaques and toxins A and B are proteinase neurotoxins.

[Myrddin]

We had lots of aluminum cookware around the house. Some of it was used for cooking spaghetti sauce. The tomato acid never agreed with my stomach. Being allergic to wheat didn't help either. I avoided the spaghetti, but my dad was a big fan of the stuff.

When I was looking through the diabetes/alzheimer's hits from Google, I noticed a relationship between diabetes and macular degeneration. My dad fed the big carbohydrate bomb to my mom every morning as well. She doesn't appear to have diabetes, but she does have macular degeneration. Now that dad has passed on, she eats a healthy diet. The excess weight is slowly coming off.

[MedicalMess]

I don't believe it was the sugar that did the damage! It is more complex than that. The insulin is inhibited first. This raises blood glucose levels because less sugar can be helped to penetrate into tissues. This makes it difficult for the glucose to break down into smaller sugars that become part of the glycoprotein inter-cellular defense system. This allows C. difficile to stealth the immune system so that you can't kick it out of the body. C. difficile further deactivates phagocytosis (engulfing/dissolving functions) of macrophages that do manage to show up. So what you get is an accumulation of white blood cells with no where to go also known as an autoimmune disease which diabetes is. This bug not only shuts down insulin production directly proportional to its toxin output but it can cause full-blown pancreatitis. The eyes go from macular degeneration caused by collagenase enzymes that break down the capillaries and optical rods in the back of the eye. C. difficile also inflames ducts and can cause severe optical infections so you can get glaucoma and ureitis/uvitis/iritis conjunctivitis and optic neuritis.

So as you can see it becomes a slow growth viscous cycle that continues until you find a way to intercede. One way is with the right combination of antibiotics which is very hazardous to do. The second way is to go after the toxins by blocking the damage activation sites. This is done with glyconutrients because they will bind to the toxins and disable these molecules from binding to the host cell glycoprotein defense mechanism. This breaks the immune system damage process and the body begins to fight back often with immune reactions similar to that of the flu (Jarish, Herxheimer Reaction).

[Age of Reason]

I think it was back in the 1970's when I read that aluminum cookware might be implicated in Alzheimers.

Scott and Helen Nearing claimed in their book, "Living the Good Life," that in the 1930s they avoided using aluminum cookware because cooking in it might be unhealthy.

[PGalt]

Interesting, informative thread. Thanks to all contributors.

[pepsionice]

It would seem like the "Pajama Boggers" might have more research strength at hand than the fools at some research lab in Boston.

[Quix]

FWIW,

I switched to organic non-aluminum based deoterant years ago.

Probably quite a number hereon think it was way to late but that's another issue. LOL.

[Quix]

Thanks.

BTW, paragraph are our friends.