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IN THE LAB | JANUARY 31, 2012  -  Shirley S. Wang

A New Target in Fighting Brain Disease: Metals

Research into how iron, copper, zinc and other metals work in the brain may help unlock some of the secrets of degenerative diseases like Alzheimer's and Parkinson's.

Iron and copper appear to accumulate beyond normal levels in the brains of people with these diseases, and a new, Australian study published Sunday shows reducing excess iron in the brain can alleviate Alzheimer's-like symptoms—at least in mice.

A genetic mutation related to regulating iron is linked to ALS, or Lou Gehrig's disease. Zinc, on the other hand, appears to impair memory if its levels get too low or if it gets into a brain region where it doesn't belong, as it can with traumatic brain injury.

Research into the complicated, invisible roles these metals play in brain diseases has lagged behind study of the more-visible proteins that are damaged or clump together in the brains of Alzheimer's and Parkinson's sufferers. But better understanding metals' role in the brain could help shed light on a range of medical conditions and might offer a new route for developing treatments, scientists say.

"The field is coming around to the idea of the cause of Alzheimer's being multifactorial," and disturbed metal regulation could be one of those factors, says Ralph Nixon, chairman of the Alzheimer Association's medical and scientific advisory council and director of the Silberstein Alzheimer's Institute at New York University.

Tiny metal ions—charged particles of the elements—serve several essential functions in the body, including facilitating chemical reactions to generate energy and preserving the structure of proteins. Strict checks and balances in a healthy body keep metal levels within a tight range.

But the biological changes that come with disease and aging—as opposed to poisoning from outside sources like food, supplements or metal pans—can knock levels of these metals out of whack in the brain.

Iron, for instance, is a "double-edged sword" because it interacts with oxygen to help the body generate energy, but also can produce free radicals, highly reactive molecules that can cause cell damage, says James Connor, professor and vice chairman of neurosurgery at Penn State University in Hershey.

If the body has too little iron, such as with anemia, the body doesn't generate enough energy to sustain important functions. But an overabundance of iron accumulated in the brain is toxic. Significantly higher accumulations of metal have been observed in the brains of people with Parkinson's and Alzheimer's disease than in healthy people of the same age, says Ashley Bush, a professor of pathology at the University of Melbourne.

The new study, conducted by Dr. Bush and colleagues and published in the journal Nature Medicine, examined the amount of iron in the brains of mice that were bred unable to produce the tau protein, which helps stabilize the structure of neurons. Tau damage is associated with Alzheimer's and Parkinson's.

As the mice aged, they suffered symptoms similar to people with both diseases, including impaired short-term memory, and also exhibited an accumulation of iron in their brains. When the researchers gave them a drug removing excess iron, the symptoms reversed. This means normally functioning tau is necessary for removing iron in the brain, Dr. Bush says. The finding bolsters previous research showing that bringing down iron may be a path to new treatments.

"An accumulation of iron in neurons seems to be a final end-stage event in neurodegeneration, whether it be Alzheimer's or Parkinson's, [or] any [condition] related to tau abnormalities," says Dr. Bush, who is also a fellow at the university's Mental Health Research Institute.

Other proteins affected in Alzheimer's also play a role in metal regulation. The amyloid precursor protein is important in helping export iron from the brain, according to work published in the journal Cell in 2010. Presenilin, another protein that aids in metal uptake, is also disturbed in diseased brains, according to a study published in Journal of Biological Chemistry last year.

Similar findings link copper accumulation and brain disease, though not as much research has been conducted as with iron, scientists say.

In addition to iron accrual, lower-than-normal levels of zinc have been found in patients with Alzheimer's and Parkinson's disease, according to work by George Brewer, an emeritus professor at the University of Michigan, and Edward Fitzgerald at the University at Albany-SUNY, published last year in the American Journal of Alzheimer's Disease and Other Dementias. Dr. Brewer now is a consultant to Adeona Pharmaceuticals Inc., based in Ann Arbor, Mich., which is developing a zinc-based treatment for Alzheimer's, he says.

Besides Adeona, a handful of other biotechnology companies have also been testing experimental metal-lowering drugs for treatment of Alzheimer's or Parkinson's. But developing such drugs is tricky because it is hard to target metals in specific parts of the brain. Simply lowering or increasing the amount overall in the body may not be beneficial, researchers say.

Metals may play a vital role in other brain conditions.

Stephen Lippard, a chemistry professor at the Massachusetts Institute of Technology, and colleagues from Duke University and the University of Toronto, found zinc helps neurons communicate in the hippocampus, a brain region involved in learning and memory. Disturbing this interaction, or ushering zinc into a brain region where it doesn't belong, could affect memory formation and the occurrence of epileptic seizures, says Dr. Lippard, who studies the role of metal ions in biology, neuroscience, and medicine. Their work was published in September in Neuron.

"It's important that the medical community continue to be alerted to the connection between metal ions and neurological disease," says Dr. Lippard.

Dr. Connor and his Penn State team have shown that patients with ALS have a higher rate of mutation in a gene, HFE, that regulates iron absorption. Carriers of the mutation have higher levels of iron in the brain and a fourfold increase in risk of ALS, according to a 2004 study published in the Journal of Neurological Sciences.

They have also been trying to figure out why the patients with multiple sclerosis lose the protective coating, called myelin, surrounding their axons, the part of the nerve cell that conducts electrical impulses. The cells responsible for making the myelin have elevated iron, making them more vulnerable to damage and death, says Dr. Connor.

Metals, Positive and Negative

Several metals play vital roles in the human body, but diseases can disturb their balance, causing harm.


Normal function: Involved in oxygen transport; needed to make energy for cells.

In the brain: Excess levels of iron are linked to Alzheimer's and Parkinson's diseases. Proteins and mutations related to iron delivery or absorption appear to be connected to Lou Gehrig's disease and multiple sclerosis.


Normal function: Helps transport oxygen, often works in tandem with iron.

In the brain: Wilson disease stops the body from getting rid of copper, which can cause speech problems, tremors and muscle stiffness. Disruption in copper regulation causes Menkes disease, which leads to abnormally low copper levels.


Normal function: Helps make DNA and RNA, regulates cell death, and plays a role in short-term memory and learning.

In the brain: Low levels or the presence of the metal in areas of the brain where it isn't normally found are thought to impair memory.

Toxic towns: People of Mossville 'are like an experiment'

By David S. Martin, CNN Medical Senior Producer

Westlake, Louisiana (CNN) -- Gather current and former Mossville, Louisiana, residents in a room and you're likely to hear a litany of health problems and a list of friends and relatives who died young.

"I got cancer. My dad had cancer. In fact, he died of cancer. It's a lot of people in this area who died of cancer," says Herman Singleton Jr., 51, who also lost two uncles and an aunt to cancer.

Singleton and many others in this predominantly African-American community in southwest Louisiana suspect the 14 chemical plants nearby have played a role in the cancer and other diseases they say have ravaged the area.

For decades, Mossville residents have complained about their health problems to industry, and to state and federal agencies. Now with a new Environmental Protection Agency administrator outspoken about her commitment to environmental justice, expectations are growing.

"I'm pretty hopeful now," say Debra Ramirez, 55, who grew up in Mossville and who lost a sister at 45 of sarcoidosis, an inflammatory disease. "I do see her trying to do the right thing."

Lisa Jackson, a native of New Orleans, Louisiana, and the first African-American administrator of the EPA, this year listed environmental justice as one of her seven priorities.

And the EPA held a meeting in Mossville last month formally kicking off a study designed to see if the community qualifies as a Superfund site, reserved for the most polluted places in the United States. Superfund site designation would bring federal funding for cleaning up Mossville.

Mossville Environmental Action Now (MEAN), the local environmental group, has asked government and industry to relocate residents who want to leave, offer a free health clinic and lower emissions from the plants. Superfund relocates residents only as a last resort.

"There are people that are getting sick; there are people who are dying because of what is happening in our community. These chemicals are killing us. They will destroy Mossville if nothing happens," says Dorothy Felix of MEAN.

Thousands of pounds of carcinogens such as benzene and vinyl chloride are released from the facilities near Mossville each year, according to the EPA's Toxic Release Inventory.

Chemical boom

The industrial boom began in and around Mossville during World War II. Vinyl chloride makers, refineries, a coal-fired energy plant and chemical plants now operate in what was once rural country, rich in agriculture, fishing and hunting.

Robert Bullard, author of "Dumping in Dixie," says it's no surprise industry chose Mossvillle, an unincorporated community founded by African Americans in the 1790s.

"What happens is zoning becomes very political, and what happens is people with power, with lawyers and elected officials who can fight for them and make decisions for them, oftentimes will get things placed away from them and placed in locations where other people live" Bullard says.

Without the power, Bullard says, African-Americans have borne the brunt of living near industry, landfills and hazardous facilities.

"African Americans are more than 79 percent more likely to live in communities where there are dangerous facilities that pose health threats," says Bullard, director of the Environmental Justice Resource Center at Clark Atlanta University.

Bullard says Jackson has breathed new life into environmental justice since she took office last year. During the previous eight years, he says, "environmental justice was non-existent or invisible."

Mossville fears

Over time, Mossville residents became worried emissions from the plants were affecting their health.

Those fears heightened in 1998 when the federal Agency for Toxic Substances and Disease Registry tested the blood of 28 Mossville residents and found dioxin levels three times the national average.

Dioxins are carcinogens. Volcanoes and forest fires create dioxins naturally. They are also released during vinyl chloride production, at waste incinerators and by wood processing facilities.

Residents were retested for dioxins in 2001, with similar results, but in 2006 the agency concluded that residents did not face a health risk, an assessment echoed by local industry.

"The emissions from the plants are within the standards set by the various agencies, and they are of a level that they have no ill effects on the local community," says Larry DeRoussel, executive director of the Lake Area Industry Alliance.

DeRoussel speaks for local industry. CNN invited all 14 companies to speak on camera. None of them accepted; some said interviewing DeRoussel would suffice.

DeRoussel points to statistics showing the cancer rate in Calcasieu Parish, the local county, is not significantly higher than the state average.

But Wilma Subra, a chemist from New Iberia, Louisiana, who has worked with Mossville residents, says the statistics are misleading because the parish covers such a large area, more than 1,000 square miles, and more than 180,000 residents. Mossville is a tiny fraction of that, with about 375 homes adjacent to the chemical plants.

"The people of Mossville are like an experiment. They know that they have high levels of dioxin in their blood, and they're allowed to continue to live there and be exposed," says Subra, recipient of the MacArthur genius grant in 1999 for her environmental work with communities.

After the EPA announced its Superfund investigation, Felix says she's hopeful for the first time in years Mossville will be saved.

"This is the first time I've had a little hope in EPA," Felix says.

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Research links pesticides with ADHD in children


CHICAGO – A new analysis of U.S. health data links children's attention-deficit disorder with exposure to common pesticides used on fruits and vegetables.

While the study couldn't prove that pesticides used in agriculture contribute to childhood learning problems, experts said the research is persuasive.

"I would take it quite seriously," said Virginia Rauh of Columbia University, who has studied prenatal exposure to pesticides and wasn't involved in the new study.

More research will be needed to confirm the tie, she said.

Children may be especially prone to the health risks of pesticides because they're still growing and they may consume more pesticide residue than adults relative to their body weight.

In the body, pesticides break down into compounds that can be measured in urine. Almost universally, the study found detectable levels: The compounds turned up in the urine of 94 percent of the children.

The kids with higher levels had increased chances of having ADHD, attention-deficit hyperactivity disorder, a common problem that causes students to have trouble in school. The findings were published Monday in Pediatrics.

The children may have eaten food treated with pesticides, breathed it in the air or swallowed it in their drinking water. The study didn't determine how they were exposed. Experts said it's likely children who don't live near farms are exposed through what they eat.

"Exposure is practically ubiquitous. We're all exposed," said lead author Maryse Bouchard of the University of Montreal.

She said people can limit their exposure by eating organic produce. Frozen blueberries, strawberries and celery had more pesticide residue than other foods in one government report.

A 2008 Emory University study found that in children who switched to organically grown fruits and vegetables, urine levels of pesticide compounds dropped to undetectable or close to undetectable levels.

Because of known dangers of pesticides in humans, the U.S. Environmental Protection Agency limits how much residue can stay on food. But the new study shows it's possible even tiny, allowable amounts of pesticide may affect brain chemistry, Rauh said.

The exact causes behind the children's reported ADHD though are unclear. Any number of factors could have caused the symptoms and the link with pesticides could be by chance.

The new findings are based on one-time urine samples in 1,139 children and interviews with their parents to determine which children had ADHD. The children, ages 8 to 15, took part in a government health survey in 2000-2004.

As reported by their parents, about 150 children in the study either showed the severe inattention, hyperactivity and impulsivity characteristic of ADHD, or were taking drugs to treat it.

The study dealt with one common type of pesticide called organophosphates. Levels of six pesticide compounds were measured. For the most frequent compound detected, 20 percent of the children with above-average levels had ADHD. In children with no detectable amount in their urine, 10 percent had ADHD.

"This is a well conducted study," said Dr. Lynn Goldman of the Johns Hopkins Bloomberg School of Public Health and a former EPA administrator.

Relying on one urine sample for each child, instead of multiple samples over time, wasn't ideal, Goldman said.

The study provides more evidence that the government should encourage farmers to switch to organic methods, said Margaret Reeves, senior scientist with the Pesticide Action Network, an advocacy group that's been working to end the use of many pesticides.

"It's unpardonable to allow this exposure to continue," Reeves said.

The daily green header

6 Risky Chemicals You're Carrying in Your Body


In the most comprehensive testing to date, the CDC finds Americans are exposed to 212 chemicals. Here's how to avoid six of the riskiest.

The Centers for Disease Control and Prevention has released its latest assessment of the chemicals we're all carrying around in our bodies. The biomonitoring study is the most comprehensive in the world, measuring 212 chemicals in the blood and urine of 8,000 Americans. That's more than 40% more chemicals than have ever been tested for before.

The results: You can find 212 chemicals in the blood and urine of Americans if you look for them.

But what does it mean for your health? The CDC highlighted a few chemicals because they are both widespread -- found in all or most people tested -- and potentially harmful. Here's a look at what they are and how you can try to avoid them.

Polybrominated diphenyl ethers
Better known as "flame retardants" PBDEs are used widely in all sorts of goods -- from foam furniture to electronics -- to reduce fire risk. They also accumulate in human fat, and some studies suggest they may harm the liver and kidneys as well as the neurological system. Some states, including California, Washington and Maine, have restricted the use of certain PBDEs deemed the highest health risk. Short of such bans, avoiding them is difficult because the chemicals are integrated into so many common products.

Bisphenol A
BPA, which is found in many plastics, in the lining of cans and even coating many sales receipts, was found in more than 90% of Americans tested. The health concerns about BPA are many and growing. While BPA-free products are available, it can be difficult to choose them unless you do research ahead of time. The Daily Green has a list of many products containing BPA to help.

PFOA and other perfluorinated chemicals found in most Americans are used to create heat-resistant and non-stick coatings on cookware, as well as grease-resistant food packaging and stain-resistant clothing. Studies have linked these chemicals to a range of health problems, including infertility in women, and to liver, immune system, developmental and reproductive problems in lab animals. Avoiding them can be difficult, but avoiding products that contain them is a first step.

Formed when carbohydrates are cooked at high temperatures (French fries anyone?) and as a byproduct of tobacco smoke, acrylamide and its metabolites are extremely common in Americans. While the risks of low-level exposure aren't well known, high-level exposure has caused cancer and neurological problems in lab animals and workers, respectively. Avoiding it in food comes down to food choice, storage and preparation, according to the Food and Drug Administration. Examples include boiling or baking potatoes, rather than frying them, or soaking them in water before frying; toasting bread only lightly; and moderating the drinking of coffee, which gets acrylamide in the roasting process.

The main source of mercury -- a potent neurotoxin that can lead to permanent brain damage if young children or fetuses are exposed -- continues to be contaminated fish. To avoid mercury, you have to educate yourself about which fish are safe. Several guides exist to help make a smart choice at the fish counter.

This gasoline additive has been phased out of use in the U.S., in favor of ethanol, but it still can be detected widely in American's bodies. (It has contaminated many drinking water supplies.) While the health risks are not well defined, studies have linked it to a variety of potential problems, including neurological and reproductive damage.

The good news in the CDC report is that effective regulation can really reduce harmful exposures to chemicals. Testing reveals that secondhand smoke exposure has declined 70%, for instance, and lead poisoning (as defined by the CDC; some scientists think the acceptable level is too high) now affects less than 2% of children aged 1-5.

The bad news is that, not only are Americans being exposed to many potentially harmful chemicals, in mixtures that are totally untested, but even this most comprehensive testing regimen accounts for less than 1% of the chemicals most Americans are exposed to regularly. The Environmental Protection Agency has identified at least 6,000 chemicals that Americans are routinely exposed to.

Until and unless U.S. regulation of chemicals changes, chemicals will continue to be used in commerce before rigorous safety testing. That means it's up to consumers to avoid chemicals they deem risky.

Found at:


Study: Chemicals, pollutants found in newborns

Thursday, December 3, 2009

Chemicals from cosmetics, perfumes and other fragrances were detected along with dozens of other industrial compounds in the umbilical cords of African American, Asian and Latino infants in the United States, according to a national study released Wednesday.

Laboratory tests paid for by the nonprofit Environmental Working Group and Rachel's Network found 232 chemicals and pollutants in the umbilical cords of the 10 babies tested in five states between December 2007 and June 2008.

'Not a surprise'

"It is not a surprise because studies for many years have shown synthetic and industrial chemicals in humans, but it is particularly concerning that the developing fetus is being exposed," said Megan Schwarzman, a family physician at San Francisco General Hospital and a research scientist in environmental public health at UC Berkeley. "This is a particularly vulnerable time, and there is no reason for the chemicals to be there."

It was the 11th time the working group has conducted laboratory tests of human blood for chemicals in household and industrial products. Overall, the working group, which focuses on environmental health issues, found 414 chemicals and pollutants in 186 people of all ages and races, including Caucasians.

The latest study was the first time newborns of minority mothers were exclusively tested.

Representatives of the study group admitted that the sample of newborns from California, Michigan, Florida, Massachusetts and Wisconsin was too small for them to draw any definitive conclusions about race. The results are nevertheless likely to provide new ammunition in the effort to tighten regulations of consumer products and force cosmetic companies to list their ingredients.

Seven of the 10 babies had in their umbilical cord blood synthetic musks known as Galaxolide and Tonalide, which are toxic to aquatic life and have been shown in preliminary studies to cause hormonal changes.

The musk is used in scented soaps, perfumes and colognes, indicating the infants were contaminated by cosmetics their mothers used.

"It means the chemicals are crossing the placenta and getting into babies in the womb," said Stacy Malkan, a member of San Francisco's Campaign for Safe Cosmetics and the author of "Not Just a Pretty Face: The Ugly Side of the Beauty Industry."

Another chemical found in the umbilical cords was bisphenol A, or BPA, a synthetic estrogen used in plastics that has been linked to breast cancer and hormonal problems. A study of Chinese factory workers released last month found an increased risk of sexual dysfunction from exposure to large amounts of the chemical.

It was the first time the synthetic musks and BPA were found in newborns.

Products used in flame retardants, rocket fuels, on frying pans and in computer circuit boards were found in the infants in addition to lead, mercury and known carcinogens, according to the study.

Despite this stark evidence of contamination, cosmetics companies do not have to list synthetic chemicals in their products because fragrances are considered trade secrets.

Not listed

"You won't find these chemicals on the label of your favorite perfume because companies don't have to tell us what is in a fragrance," Malkan said. "That's just wrong. Consumers have the right to know what chemicals we are putting into our bodies."

On Wednesday, California and 12 other states issued a joint statement saying federal laws designed to protect the public from toxic chemicals are too weak. The statement asked for changes that would protect vulnerable populations by identifying and regulating the chemicals in consumer products.

The cosmetic industry and petrochemical companies have fought efforts in Congress to reform cosmetic industry regulations, which were first drawn up in 1938 and have remained virtually unchanged.

Both the House and Senate are considering bills to ban bisphenol A in food and beverage containers. The bills, by Sen. Dianne Feinstein, D-Calif., and Rep. Edward Markey, D-Mass., would protect pregnant women, their children and other consumers from the hormone-disrupting chemical that is used in plastic baby bottles, food containers and in the lining of food cans.

The Environmental Working Group study urges immediate action to prevent further exposure to chemicals.

"Each time we look for the latest chemical of concern in infant cord blood, we find it," said Anila Jacob, the group's senior scientist and co-author of the report. "Our results strongly suggest that the health of all children is threatened by trace amounts of hundreds of synthetic chemicals coursing through their bodies from the earliest stages of life."

Washington Post

Study Finds High-Fructose Corn Syrup Contains Mercury

Wednesday, January 28, 2009 

MONDAY, Jan. 26 (HealthDay News) -- Almost half of tested samples of commercial high-fructose corn syrup (HFCS) contained mercury, which was also found in nearly a third of 55 popular brand-name food and beverage products where HFCS is the first- or second-highest labeled ingredient, according to two new U.S. studies.

HFCS has replaced sugar as the sweetener in many beverages and foods such as breads, cereals, breakfast bars, lunch meats, yogurts, soups and condiments. On average, Americans consume about 12 teaspoons per day of HFCS, but teens and other high consumers can take in 80 percent more HFCS than average.

"Mercury is toxic in all its forms. Given how much high-fructose corn syrup is consumed by children, it could be a significant additional source of mercury never before considered. We are calling for immediate changes by industry and the [U.S. Food and Drug Administration] to help stop this avoidable mercury contamination of the food supply," the Institute for Agriculture and Trade Policy's Dr. David Wallinga, a co-author of both studies, said in a prepared statement.

In the first study, published in current issue of Environmental Health, researchers found detectable levels of mercury in nine of 20 samples of commercial HFCS.

And in the second study, the Institute for Agriculture and Trade Policy (IATP), a non-profit watchdog group, found that nearly one in three of 55 brand-name foods contained mercury. The chemical was found most commonly in HFCS-containing dairy products, dressings and condiments.

But an organization representing the refiners is disputing the results published in Environmental Health.

"This study appears to be based on outdated information of dubious significance," said Audrae Erickson, president of the Corn Refiners Association, in a statement. "Our industry has used mercury-free versions of the two re-agents mentioned in the study, hydrochloric acid and caustic soda, for several years. These mercury-free re-agents perform important functions, including adjusting pH balances."

However, the IATP told the Minneapolis Star Tribune that four plants in Georgia, Tennessee, Ohio and West Virginia still use "mercury-cell" technology that can lead to contamination.

IATP's Ben Lilliston also told HealthDay that the Environmental Health findings were based on information gathered by the FDA in 2005.

And the group's own study, while not peer-reviewed, was based on products "bought off the shelf in the autumn of 2008," Lilliston added.

The use of mercury-contaminated caustic soda in the production of HFCS is common. The contamination occurs when mercury cells are used to produce caustic soda.

"The bad news is that nobody knows whether or not their soda or snack food contains HFCS made from ingredients like caustic soda contaminated with mercury. The good news is that mercury-free HFCS ingredients exist. Food companies just need a good push to only use those ingredients," Wallinga said in his prepared statement.

More information

The U.S. Agency for Toxic Substances & Disease Registry has more about mercury and health.

SOURCE: Institute for Agriculture and Trade Policy, news release, Jan. 26, 2009

Washington Post

Detox from Mercury with these products


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