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Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage

WASHINGTON, Sept. 26 2007 — Consuming large amounts of caffeine while taking acetaminophen, one of the most widely used painkillers in the United States, could potentially cause liver damage, according to a preliminary laboratory study reported in the Oct. 15 print issue of ACS’ Chemical Research in Toxicology, a monthly journal. The toxic interaction could occur not only from drinking caffeinated beverages while taking the painkiller but also from using large amounts of medications that intentionally combine caffeine and acetaminophen for the treatment of migraine headaches, menstrual discomfort and other conditions, the researchers say.

Health experts have warned for years that consuming excess alcohol while taking acetaminophen can trigger toxic interactions and cause liver damage and even death. However, this is the first time scientists have reported a potentially harmful interaction while taking the painkiller with caffeine, the researchers say.

While the studies are preliminary findings conducted in bacteria and laboratory animals, they suggest that consumers may want to limit caffeine intake — including energy drinks and strong coffee — while taking acetaminophen.

Chemist Sid Nelson, Ph.D., and colleagues, of the University of Washington in Seattle, tested the effects of acetaminophen and caffeine on E. coli bacteria genetically engineered to express a key human enzyme in the liver that detoxifies many prescription and nonprescription drugs. The researchers found that caffeine triples the amount of a toxic byproduct, N-acetyl-p-benzoquinone imine (NAPQI), that the enzyme produces while breaking down acetaminophen. This same toxin is responsible for liver damage and failure in toxic alcohol-acetaminophen interactions, they say.

In previous studies, the same researchers showed that high doses of caffeine can increase the severity of liver damage in rats with acetaminophen-induced liver damage, thus supporting the current finding.

“People should be informed about this potentially harmful interaction,” Nelson says. “The bottom line is that you don’t have to stop taking acetaminophen or stop taking caffeine products, but you do need to monitor your intake more carefully when taking them together, especially if you drink alcohol.”

Nelson points out that the bacteria used in the study were exposed to ‘megadoses’ of both acetaminophen and caffeine, much higher than most individuals would normally consume on a daily basis. Most people would similarly need to consume unusually high levels of these compounds together to have a dangerous effect, but the toxic threshold has not yet been determined, he says.

Certain groups may be more vulnerable to the potentially toxic interaction than others, Nelson says. This includes people who take certain anti-epileptic medications, including carbamazepine and phenobarbital, and those who take St. John’s Wort, a popular herbal supplement. These products have been shown to boost levels of the enzyme that produces the toxic liver metabolite NAPQI, an effect that will likely be heightened when taking both acetaminophen and caffeine together, he says.

Likewise, people who drink a lot of alcohol may be at increased risk for the toxic interaction, Nelson says. That’s because alcohol can trigger the production of yet another liver enzyme that produces the liver toxin NAPQI. The risks are also higher for those who take large amounts of medications that combine both acetaminophen and caffeine, which are often used together as a remedy for migraine headaches, arthritis and other conditions.

The researchers are currently studying the mechanism by which this toxic interaction occurs and are considering human studies in the future, they say. The National Institutes of Health funded the initial animal and bacterial studies.

The American Chemical Society — the world’s largest scientific society — is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

— Mark T. Sampson

*Embargo Terms
Contents of this release are strictly embargoed by the ACS, which has sole authority to alter the release time. Wire service stories must carry the embargo time, and wire stories on the press release topic may not be distributed more than 24 hours before that time. Solely to solicit expert comment, news media may show relevant parts of this document, and the paper to which it refers, to independent specialists. However, they must ensure in advance the embargo conditions will be honored. The research in this press release is from a copyrighted publication, and stories must credit the journal by name. Anyone using advance information for stocks or securities dealing may be guilty of insider trading under the federal Securities Exchange Act of 1934. For questions or assistance, please use the news media contact, above.

“Cooperative Binding of Acetaminophen and Caffeine within the P450 3A4 Active Site,” tx7000702
Print publication date: Oct. 15, 2007
ASAP (online) date: 9-26-07

Contact: Michael Bernstein
American Chemical Society

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September 26, 2007 Posted by | Acetaminophen and Caffeine, American Chemical Society, Global Health Vision, Global News, Health, News, Preventive Medicine, RSS Feed, WASHINGTON | 2 Comments

Research links genetic mutations to lupus

WINSTON-SALEM, N.C. – A gene discovered by scientists at Wake Forest University School of Medicine has been linked to lupus and related autoimmune diseases. The finding, reported in the current issue of Nature Genetics, is the latest in a series of revelations that shed new light on what goes wrong in human cells to cause the diseases.

“This research is a huge leap toward understanding the cause of lupus and related autoimmune diseases,” said Fred Perrino, Ph.D., a co-author on the paper and a professor of biochemistry at Wake Forest. “There had been few clues before now.”

Perrino, who discovered the gene in 1998, said he suspected it was involved in human disease, but it took a group of researchers from around the world collaborating to put the puzzle together.

“We’ve known that lupus was a complex disease, but now we have a specific protein and a particular cellular process that appears to be one of the causes,” said Perrino. “We’re connecting the dots to understand the biology of what’s going on with the disease.”

In Nature Genetics, lead author Min Ae Lee-Kirsch, M.D., from the Technische Universität Dresden in Dresden, Germany, and colleagues report finding variations of the TREX1 gene discovered by Perrino in patients with systemic lupus erythematosus. The study involved 417 lupus patients from the United Kingdom and Germany. Mutations were found in nine patients with lupus and were absent in 1,712 people without lupus.

“Our data identify a stronger risk for developing lupus in patients that carry variants of the gene,” said Lee-Kirsch.

In recent years, the gene was also linked to Aicardi-Goutieres syndrome, a rare neurological disease that causes death in infants, and to chilblain lupus, an inherited disease associated with painful bluish-red skin lesions that occur during cold weather and usually improve in summer. The current research also links it to Sjogren’s syndrome, a form of lupus.

The diseases are all autoimmuine diseases, which means that the body makes antibodies against itself. In lupus, these antibodies cause pain and inflammation in various parts of the body, including the skin, joints, heart, lungs, blood, kidneys and brain. The disease is characterized by pain, heat, redness, swelling and loss of function.

Perrino began studying the protein made by the gene more than 14 years ago.

“We basically cracked open cells to locate the protein and find the gene,” said Perrino. “In the 14 years since, we’ve learned a lot about the protein and how it functions.”

The gene manufactures a protein, also known as TREX1, whose function is to “disassemble” or “unravel” DNA, the strand of genetic material that controls processes within cells. The “unraveling” occurs during the natural process of cells dying and being replaced by new cells. If a cell’s DNA isn’t degraded or unraveled during cell death, the body develops antibodies against it.

“If the TREX1 protein isn’t working to disassemble the DNA, you make antibodies to your own DNA and can end up with a disease like lupus,” said Perrino.

Perrino and colleagues at Wake Forest have been studying the gene and its protein since 1993. Thomas Hollis, Ph.D., an assistant professor of biochemistry at Wake Forest, is credited with solving the structure of both TREX1 and a similar protein, TREX2. Perrino has also developed a way to measure the function of the proteins.

In a study reported in April in the Journal of Biological Chemistry, Hollis and Perrino found that three variations of the gene reduced the activity of the protein by four- to 35,000-fold.

“Now that we have the structure, we can understand how it disassembles DNA and how mutations in the gene may affect that process,” said Hollis.

The researchers hope that understanding more about the gene’s mutations and the structure of the protein may lead to drug treatments to help ensure that mutant copies of the gene are inactive.

Media Contacts: Karen Richardson,; Shannon Koontz,; at 336-716-4587.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in primary care and 44th in research among the nation’s medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.

Contact: Karen Richardson
Wake Forest University Baptist Medical Center

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A new century of Alzheimer’s disease research

Mayo Clinic scientists aim to improve risk prediction, diagnosis and treatment
JACKSONVILLE, Fla. — Imagine the day when a routine visit to the family doctor includes a simple blood test to predict the risk for developing Alzheimer’s disease (AD). If the test returns a worrisome result — too many sticky brain proteins that might begin to gum up memory and thought in 10 to 15 years — a person could be offered an aspirin-like pill to keep those proteins in check.

That is the future a visionary team of researchers at Mayo Clinic’s campus in Jacksonville aims to reach.

“It will be very straightforward, like today’s blood cholesterol test to gauge risk of developing heart disease,” says Steve Younkin, M.D., Ph.D., a Mayo Clinic neuroscientist. “If your cholesterol profile is out of whack, treatment with a simple statin drug can reduce that risk. Our goal is to develop a similar kind of testing and treatment to keep the brain in balance.”

Researchers and physicians at Mayo Clinic’s sites in Florida, Minnesota and Arizona are studying various aspects of Alzheimer’s. When combined, the elements provide a comprehensive approach to unraveling the mystery of the disease: from understanding why it develops, to how it can be diagnosed early, treated effectively and, ultimately, prevented.

Much of the basic lab, animal research and drug discovery occurs in Jacksonville. Mayo researchers in Jacksonville, Rochester, Minn., and Scottsdale, Ariz., are studying aging’s effects in thousands of elderly individuals. Researchers want to know how aging changes brain structure, thought processes and blood chemistry, so they can model and predict progression to Alzheimer’s disease.

“Whether it is working with people or doing lab science, we have really tried to focus our research on ways in which we can make a difference in the lives of our patients, both today and tomorrow,” says Todd Golde, M.D., an Alzheimer’s disease researcher who chairs the Department of Neurosciences at Mayo Clinic Jacksonville.

And, by all accounts, that focus will likely begin to pay off in this second century of Alzheimer’s research. Until 1986, some 80 years after German physician Alois Alzheimer discovered the brain abnormalities associated with the disease, physicians understood little about Alzheimer’s disease. But several decades ago, the pace of discovery began to accelerate, says Ronald Petersen, M.D., Ph.D., a Mayo physician in Rochester who directs the Mayo Clinic Alzheimer’s Disease Research Center (ADRC), encompassing the research programs in Jacksonville and Rochester.

“We have moved a great distance forward in understanding what might be the key, or, in the least, an important aspect of this disease,” Dr. Petersen says. “And we are at the threshold of developing therapies that we hope will eventually impact Alzheimer’s disease.”

“We are not slogging through a fog anymore,” says Dr. Younkin, who has helped define the direction that Alzheimer’s research has taken in many of the world’s research labs. “We can see the top of the hill for the first time, and while we probably won’t get where we want to be for many years, it is really exciting.” Dr. Younkin helped discover that a single brain protein, known as amyloid-beta 42 (AB42), appears to be the central player in the disorder. And much of Alzheimer’s drug research is focused on different ways to attack Aâ42, believed to be the most vulnerable target — the Achilles’ heel — of Alzheimer’s disease.

“We know AB42 is always on the scene and is clearly important,” says Richard Caselli, M.D., who heads Alzheimer’s disease research at Mayo Clinic in Arizona. “So the prevailing model is that AB42 is it, and if you can somehow control AB42, you can control Alzheimer’s disease.”

Protein provides initial “insult”

Today, an estimated 20 million people worldwide have Alzheimer’s disease. Within the higher-functioning portions of their brains (the areas responsible for thought and memory), twisting tangles of threads made up of chains of tiny “tau” proteins are being assembled inside billions of nerve cells (neurons). Outside the neurons, other amyloid-beta (AB) proteins are fusing together into sticky clumps (plaque) — akin to the substance that clogs heart arteries. Together, these tangles and plaques disrupt the normal functioning of the nerve cells, destroying the pathways along which packets of chemical “information” move. Memories cannot be stored or retrieved, and, eventually, the brain cannot control the body. Each year about 4.6 million more people develop Alzheimer’s worldwide, and that number is escalating rapidly. As many as 4.5 million people in the United States have Alzheimer’s, according to the National Institute on Aging, and experts predict that by 2050 that total will rise to approximately 15 million people.

To find out what causes Alzheimer’s — plaques, tangles or both — researchers first began studying people who developed the disease early, before age 65. A breakthrough came when the gene that produced the AB fragments (amyloid-beta precursor protein, or APP) was found on chromosome 21. This made sense, because patients with Down syndrome, all of whom inherit an extra chromosome 21, typically develop early brain plaques and tangles.

Then scientists linked mutations in two other genes to early-onset Alzheimer’s, and these two genes were involved in the production of AB. In 1995, Dr. Younkin and Harvard researcher Dennis Selkoe, M.D., independently found that all three of these mutations increase the production of either AB in general, or a particular type of AB that is made up of 42 amino acids — just slightly longer than the typical 40 amino acid AB fragment.

Dr. Younkin’s finding was pivotal, made just as the scientist moved his laboratory from Case Western Reserve to Mayo Clinic’s campus in Jacksonville. An avalanche of confirmatory studies was soon published, and the Alzheimer’s research world quickly turned its attention to figuring out ways to disrupt AB production. Some researchers, such as Dr. Younkin, believed that in the brains of people who have Alzheimer’s, AB42 is deposited first, providing the initial toxic damage that leads to plaque formation, and then to disruption of tau inside neurons. The concept is known as the amyloid cascade hypothesis and is now accepted by many Alzheimer’s researchers almost as a gospel truth.

Early laboratory analysis of AB42 showed that the extra two molecules seemed to form a hook on the amyloid protein, making it more likely to stick to other amyloid proteins in the brain. Thus, researchers concluded that AB42 is highly prone to forming deposits. Synthesized particles of AB42 will fuse to each other within hours in an animal’s brain, but weeks are required for AB40 to adhere. More recent research has shown that the AB42 protein folds in such a way that it creates a pleated-sheet-like “template” that acts to chemically attract other proteins, and together these proteins grow in a crystalline fashion like a snowball emerging from a single icy flake.

“With a potential target, many in the pharmaceutical industry who want to design treatments for AD began bearing down on the issue, and that effort has completely turned around the prospects of finding something that could eventually help our patients,” Dr. Younkin says.

Now more than 100 mutations have been found in the three genes that cause early Alzheimer’s, and all increase production of AB42.

Of the AB produced normally in humans, 5 percent to 20 percent is AB42. As people grow older, small numbers of plaques and tangles form. The risk that these lesions will cause dementia increases with age; half of all people 85 and older are believed to have some stage of Alzheimer’s. Researchers think this common form of Alzheimer’s is triggered by a combination of normal genetic susceptibilities and other damage, such as from head trauma or unknown environmental insults. Slowly, AB40 and AB42 build up in the brain and begin to disrupt the thoughts and memories that define who we are.

Ratios predict risk

Dr. Younkin joined a core group of researchers and physicians at Mayo Clinic already collaborating to study the basic biology of the disease and methods of caring for patients who have the disorder. Based on the knowledge that Alzheimer’s is a disease of tau tangles as well as AB plaque, these scientists were already developing a mouse that spontaneously overproduces tau proteins.

Mayo Clinic researchers were the first to genetically engineer a mouse to express a mutation of the gene that controls tau production, and in 2000 they reported in Nature Genetics that the “tau” mouse develops the same kind of neurofibrillary tangles seen in human dementia. In 2001, the Mayo Clinic team produced another new engineered mouse, the first to exhibit tangles as well as the two forms of plaque (AB40 and AB42). In the journal Science, Michael Hutton, Ph.D., Dennis Dickson, M.D., Jada Lewis, Ph.D., Shu-Hui Yen, Ph.D., and Eileen McGowan, Ph.D., presented the mouse model, saying it is the best animal model possible to test therapies aimed at slowing down, or halting, neurodegeneration.

The engineered mouse strengthened the notion that development of tangles followed that of plaque. The tangle pathology was enhanced in regions where the plaque occurred, says Dr. Hutton, a neurobiologist. But what was also interesting was that these mice, the ones that also developed plaque, produced more tau than did mice with only a tau mutation. “That proved that there is an interaction between tau and amyloid, and it is that interaction that causes cognitive deficits,” he says.

These Mayo mice are offered to any scientist studying Alzheimer’s disease for just the cost of producing them. They are also made available to pharmaceutical companies to help them test whether the drugs they are developing could reduce the production of tangles and/or plaque.

The mouse models helped provide a breakthrough discovery for the Mayo Clinic researchers.

Physicians at the three Mayo Clinic sites have been collecting blood from thousands of Alzheimer’s patients, as well as study participants who do not have the disease, to determine how blood chemistry changes over the years (see associated story, Defining Alzheimer’s disease risk with the help of thousands). With support from the National Institutes of Health, they had been examining blood serum for evidence of protein “markers” that could help predict which people would develop the disease over time. One marker is AB.

Although no one knows what the normal function of AB is, the Mayo Clinic researchers found that it could be measured in blood, and that levels of both AB40 and AB42 varied in people who developed the disease. What they discovered through this analysis, however, surprised them, says Neill Graff-Radford, M.D., who heads the ADRC’s Memory Disorder Clinic and has led the work on a blood test designed to predict a person’s risk of developing Alzheimer’s.

“Levels of both AB40 and AB42 in the blood rise as a person gets older, but then, in some people, AB42 decreases,” he says. Turning to the transgenic mice, the researchers found that as soon as plaque began to develop in the brain, levels of AB42 decreased in the blood and spinal fluid.

Drs. Graff-Radford and Younkin had expected aging and genetic-related overproduction of AB42 — the insult that leads of Alzheimer’s development — would be reflected in blood samples. But sitting together in a room, looking at the charts that lead statistician Julia Crook, Ph.D., put together, the researchers experienced a classic “a-ha” moment. They saw it. The researchers realized that levels of AB42 had dropped because the protein was being sopped up, absorbed, by quickly forming plaques. In contrast, they discovered that at the same time, plasma levels of AB40 either continued to increase or decline much slower than AB42.

Drs. Graff-Radford, Younkin and Crook found that a low level of AB42 and a higher level of AB40 in blood could be seen three to five years before symptoms of the disease occurred. From these data, the Mayo Clinic researchers determined a scale of ratios for determining when symptoms will begin: two, four, or eight to 10 years.

“This blood test reflects some of the risks of who is going to develop the disease and when it is going to show up,” says Dr. Graff-Radford. “The crucial point is that it could eventually offer us a predictive test.”

The Mayo Clinic team is continuing to “follow the blood” of 2,000 participants in Rochester, and 1,000 in Jacksonville.

But the researchers know that if their AB40/AB42 ratio blood test ultimately can predict who will develop Alzheimer’s disease, people won’t be interested in knowing their risk unless something can be done to reduce that risk.

A pill a day keeps Alzheimer’s away

In the late 1990s, Dr. Golde’s research group as well as other investigators discovered that compounds that inhibited production of AB actually inhibited AB40 more than AB42. As AB42 appeared to be the real culprit in Alzheimer’s, Dr. Golde was convinced that a systematic search for compounds that preferentially lowered AB42 would be successful. However, a two-year effort did not find such a compound.

Then in 2000, Dr. Golde and Eddie Koo, M.D., who worked at the University of California, San Diego, screened several nonsteroidal anti-inflammatory drugs (NSAIDs) at high concentrations. To their surprise, they found that while some NSAIDs, such as naproxen and aspirin, had no effect on AB42, others, such as ibuprofen and indomethacin, did.

The possible significance of this finding was immediately apparent, Dr. Golde says. Large population studies had hinted that people who have used NSAIDs had a lower risk of developing Alzheimer’s. While scientists thought these NSAIDs might be reducing inflammation in the brain — and there is a lot of it in a brain with Alzheimer’s — Drs. Golde and Koo wondered if any might be working to prevent the development of Alzheimer’s by selectively inhibiting production of AB42.

Still, Drs. Golde and Koo realized that, regardless of how NSAIDs might be working to decrease the risk of developing Alzheimer’s, conducting clinical trials of NSAIDs in populations at risk for Alzheimer’s or in those with the disease would be difficult. Long-term use of high-dose NSAIDs can cause stomach ulcers, kidney damage and gastrointestinal bleeding in anyone, and those side effects would be even more prevalent in the elderly. Moreover, if NSAIDs were working by lowering AB42, Dr. Golde knew very high doses of the NSAIDs would be needed to make a difference in Alzheimer’s risk.

This meant that a compound that could successfully and significantly lower AB42 must be one without such severe side effects. So, the first NSAIDs that Drs. Golde and Koo screened were known as COX2 inhibitors because they were believed to be safer. (NSAIDs reduce inflammation because they target enzymes that are known as cyclooxygenases or COX, and classic NSAIDs, such as ibuprofen and indomethacin, nonselectively inhibit the two types of COX enzymes, COX1 and COX2.)

But, again to their surprise, Drs. Golde and Koo found that many COX2 inhibitors actually had the opposite effect on AB42 — rather then decreasing it, they increased it. The investigators then expanded their search to look more closely at compounds related to NSAIDs that might lower AB42 but result in greatly reduced COX activity.

So they tested a compound called r-flurbiprofen.

R-flurbiprofen is the mirror image of the COX-inhibiting drug s-flurbiprofen, but because it is structurally distinct (much as a person’s right and left hands have the same overall structure but cannot be superimposed on each other), it does not inhibit COX enzymes. The result was, finally, encouraging — r-flurbiprofen inhibited AB42 production both in cells and in the brains of mice.

As it happened, the biotech firm Myriad Genetics was testing r-flurbiprofen to treat prostate cancer, because the agent had shown it could reduce the size of tumors in mice studies. Armed with additional data that r-flurbiprofen decreased AB levels in an Alzheimer’s mouse model and improved the cognitive deficits found in that model, Drs. Golde and Koo personally approached the drug company to encourage them to test r-flurbiprofen in Alzheimer’s disease.

Myriad Genetics agreed, and in 2006 the company reported results from a phase II clinical trial enrolling 207 patients with mild Alzheimer’s. The study found that r-flurbiprofen produced functional and cognitive improvements, ranging from 34 percent to 48 percent, in patients who took the highest dose, 1,600 milligrams a day. “And it was remarkably safe,” says Dr. Golde. “It was much better tolerated in humans than it was in mice.” There was also evidence that the drug not only improved symptoms but may have actually slowed the course of disease, he says. Current drugs offered to Alzheimer’s patients only relieve symptoms.

Based on these findings, Myriad Genetics launched a 1,600-participant phase III clinical trial in the summer of 2006, describing it as the largest placebo-controlled study ever to be undertaken of an investigational medicine in patients with Alzheimer’s. Patients will use r-flurbiprofen (known now as Flurizan) for 18 months.

Dr. Golde, who is not involved in this trial, suspects that r-flurbiprofen will show some benefit, but that newer, designer AB42-lowering agents might be better. “A more potent drug would likely be more effective, but it will take a long time to develop such a second-generation drug,” he says. “The beauty of r-flurbiprofen is that it can be on the market quickly.”

Dr. Golde stresses a cautionary note. He worries that because of these findings, people with Alzheimer’s, or those who are at risk for developing the disease, might decide to take high doses of an over-the-counter AB42-lowering NSAID, such as ibuprofen. Because of the side effects associated with NSAID use, this could be quite harmful, he says. Indeed, because it does not inhibit COX at therapeutic levels, r-flurbiprofen is not an NSAID, whereas flurbiprofen is, he adds.

AB42-lowering agents may turn out to be “either a magic bullet or a magic shotgun,” he says. “They might be lowering AB42, reducing inflammation and doing five other things that we don’t know about.”

But to Mayo Clinic researchers, the big question is whether this compound, or any other similar kind of agent, can be used much earlier in people deemed to be at risk of developing Alzheimer’s.

“I think Alzheimer’s is going to be much easier to treat if you can prevent accumulation of AB in your brain, than if you try to treat it once plaques form,” Dr. Golde says. “We know that statins don’t work very well if a heart artery is 99 percent blocked, but do if they are taken earlier. The same thing would go for a drug designed to prevent Alzheimer’s.”

If r-flurbiprofen shows solid benefit in the phase III clinical trial, then it could be tested as a preventive agent, Dr. Golde says. But he adds that this “could possibly be the costliest trial ever to be conducted,” because it would take decades and involve thousands of people. However, Dr. Golde and his clinical colleagues share a common goal: to eventually conduct cost-effective prevention trials.

Restoring memory via tau

Mayo Clinic researchers also are working to prevent additional damage from occurring and to repair existing lesions in people who already have symptoms of Alzheimer’s.

In the process, they are attempting to answer the question that has stumped the Alzheimer’s research world: to what degree is AB responsible for the neurodegeneration seen in the disease”

No one knows what AB “normally” does inside the brain. “That is the biggest secret in Alzheimer’s disease research,” says Dr. Caselli. “We’d like to know what role it plays.”

And no one understands how tau interacts with AB.

Mayo Clinic researchers know a lot about tau, which helps stabilize the roadlike microtubules that run inside nerve cell bodies. In the world of neurobiology, tau is the big player, responsible for about 30 forms of neurodegeneration, including frontotemporal dementia, the second most common form of dementia after Alzheimer’s.

Alzheimer’s disease is the only form of dementia in which AB is involved.

As Alzheimer’s develops, the shape of tau molecules inside neurons changes; they begin to come off the microtubules they had once supported, and bind together into paired and twisted filaments. “The hypothesis is that AB stresses neurons, releasing cascades of signals that affect the phosphorylated state of tau bound to microtubules, causing them to be released,” says Dr. Hutton. This process proves to be toxic to the microtubules, which in turn cannot transport the molecular cargo needed to keep the neuron alive.

“Either the roads provided by the microtubules break down because of loss of tau, or tau accumulates into tangles that block these roads,” he says. “We don’t have evidence as to whether it is the tangles or the loss of tau that is causing cell death.

“The tangles we see are an end-stage event, whereas there is plenty of tau aggregation that occurs before these roadblocks appear,” says Dr. Hutton. “In any case, the brain can’t cope without tau.”

Because of the connection between AB and tau loss, the Mayo Clinic researchers believe that if AB is treated before the onset of tau damage, progression of the disease can be prevented. “We also know that tau is responsible for neuronal death, so we also have been developing ways to prevent tau toxicity, which could cause a major slowing of the disease,” Dr. Hutton says.

So the researchers turned again to their tau transgenic mouse, which features a unique on-off “switch”¬ to control the expression of the mutant gene so that the disease could be studied at both early and late stages.

During these experiments, the Mayo Clinic group and their collaborators were stunned to find that they could reverse tau pathology early on, and restore memory to mice that had started to develop cognitive problems.

But researchers were in for an even bigger surprise, Dr. Hutton says. “What was amazing, absolutely staggering in fact, is that when we aged the mice further — to the point where the pathology was quite severe, a lot of neurons had died, and the mouse couldn’t remember any of its tasks — when we hit this molecular switch, the mouse recovered a lot of its memory.”

To the research team, this demonstrated that Alzheimer’s is potentially a reversible process: that if deposition of AB is not stopped in time, then it may be possible to halt tau degradation and restore damaged nerves. “Once you get the disease, the effectiveness of AB therapy may be limited, so we hope tau will be potentially a more exciting target,” Dr. Hutton says. “If we are able to remove the blockage that is clogging microtubules, it may be that the system will just start again, with neurons back functioning normally.”

Dr. Lewis says the studies suggest that toxicity to neurons caused by tau begins before tangles develop. “If so, we may be able to repair that process so that the neuron can rebound,” she says.

Their achievement was reported in 2005 in Science.

“These tau findings changed our ideas about what the potential for recovery is in Alzheimer’s, but also about what is causing memory loss in the patients in the first place,” Dr. Hutton says. “Our mice lost between 30 percent and 50 percent of the neurons in the parts of the brain that are responsible for memory function. But, still, sufficient numbers of neurons were left so that some memory function was actually recoverable. The neurons began to work properly once the disease process was halted.”

Dr. Hutton says the tau research is five to 10 years behind AB, and the focus of the “tauologists” at Mayo Clinic is to study how tau tangles disrupt microtubules as well as how the brain recovers and removes those tangles. What they find out can be applied to all diseases of dementia in which tau is involved — and that is the majority, if not all.

Researchers also are busy using the tau mouse to test small molecules that have already been developed for other diseases that may stop tau from initially changing its chemical shape. One design for a therapeutic drug could be to inhibit the molecules involved in the abnormal phosphorylation of tau, and another might be to find a way to stabilize the microtubules. Amazingly, a cancer drug, Taxol, works to do just that, Dr. Hutton says, because stable microtubules cannot divide — which a cancer needs to do. He is working with a pharmaceutical company to see if such a cancer treatment might work for Alzheimer’s disease.

All in the genes

Many diseases spring from a person’s unique mix of genes, the variations that flow down the generations through combinations of eggs and sperm. And given the progress science has made in decoding the human genome, Dr. Younkin is convinced that some day soon researchers will have a blueprint of all the genes that raise a person’s risk of developing Alzheimer’s, even if by just a little bit here and there.

“In the world of complex genetics, this is a very exciting time,” Dr. Younkin says. He is part of a team of scientists from four institutions who just reported locating the 14th gene that has a statistically significant association with Alzheimer’s disease.

In a January 2007 online issue of Nature Genetics, the researchers reported a new gene called SORL1 (sortilin-related receptor). They found that people who inherited certain variations of SORL1 appear to have an increased risk of developing the late-onset form of Alzheimer’s. Although they have not pinpointed the exact variations, the researchers connected the gene to disease in six different groups of people, finding that Caucasians who have Alzheimer’s displayed a variation in one area of the gene’s sequence, while African-Americans, Hispanics and a group of Arabs with the disease displayed variations in a different location. Almost 7,000 people, of whom about half had the disease, were included in the analysis.

In cell culture studies, the researchers found that decreasing the amount of SORL1 protein increased the cells’ production of AB.

While SORL1 will likely turn out to be a minor contributor to Alzheimer’s disease in general, adding all such players together could ultimately provide the missing puzzle pieces that solve the disease, Dr. Younkin says.

“Alzheimer’s is a great disease for doing genetics, because there are clear indications that a person has the disease, which makes it possible to test that individual’s DNA and RNA,” he says. Those genes never change, so profiling the more than 300,000 functional inherited variations in the approximately 30,000 genes each person has can define Alzheimer’s disease’s complex genetic signature, he says.

“We can now look at the difference in gene variants between a person who has Alzheimer’s and a person who does not; an analysis like that would only take several days,” Dr. Younkin says. “If we can find those variations in thousands of people, we could begin to see which genes play important roles in Alzheimer’s disease, and these genes could possibly be targets for novel therapeutic agents.”

“It is all possible to do, which is wonderful,” he says, but adds that while Mayo Clinic is doing such analysis with the thousands of patients the institution cares for across its three sites, many more people would need to be involved.

As much as Alzheimer’s disease research has advanced in the past 20 years, Mayo Clinic researchers say caution is warranted about the future prospect of breakthrough drugs in this decade, or even the next. Dr. Petersen expresses this hesitancy. “There are a million studies that describe how things could be happening, and they make sense, but we don’t know that they are true,” he says. “We have to keep an open mind.”

Still, there has never been a better time, or a brighter outlook, for Alzheimer’s disease researchers who spend their careers trying to find an answer to this most devastating of diseases. “Before, there was a lot of faith and not a lot of science. It was like you were leading a detective-like investigation into the Alzheimer’s killer using chisels and hammers to chip away at deeply buried clues,” Dr. Golde says.

“Now we have the scientific tools and fancy machines that allow us to be so much more productive and to progressively solve this mystery,” he says. “It’s a new century.”

Defining Alzheimer’s disease risk with the help of thousands

As much as investigators worldwide are betting that the sticky plaques made up of amyloid beta (AB) fulfill the role of central villain in Alzheimer’s disease, all researchers know about cognitively normal people who, during an autopsy, were found to have brains full of the plaque.

These patients may not be as sensitive to AB’s toxic effects as others are, some scientists speculate.

But really, scientists can’t explain it.

That is why Mayo Clinic researchers in Minnesota, Florida and Arizona are enrolling thousands of individuals, including patients who do not have memory problems, people in mild cognitive decline and patients with the disease, to participate in what collectively is one of the biggest Alzheimer’s disease epidemiological research efforts in the nation.

In Rochester, which is in Olmsted County, Minn., more than 2,000 residents from 70 to 89 years old have been randomly selected and have signed up. And in Scottsdale, Ariz., 600 asymptomatic adults in their 50s and 60s are enrolled in an effort to define “normal aging.” In Jacksonville, Fla., over 1,000 individuals, including more than 350 African-Americans, are participating. Hundreds of Alzheimer’s disease patients being treated at the three Mayo campuses are also taking part.

With the generous permission of participants, researchers are routinely collecting blood samples to define genetic profiles and look for changes in blood chemistry, including proteins that are sent floating downstream from the brain.

“We want to put all this information together to create a predictive equation that can determine an individual’s risk of developing Alzheimer’s disease,” says Ronald Petersen, M.D., Ph.D., director of the Mayo Clinic Alzheimer’s Disease Research Center. “The whole idea is to move back detection of the disease process earlier and earlier.”

Such biological profiling could also help in the effort to develop and test therapeutic drugs, he says. “If we have clarified who is more likely to develop the disease, we can allocate treatment appropriately,” he says.

Much of the blood collected by Mayo Clinic in Rochester and Scottsdale is shared with researchers at Mayo Clinic in Jacksonville. “The cross-talk between these three centers is really advancing Alzheimer’s disease science,” says Richard Caselli, M.D., who heads Alzheimer’s disease research at Mayo Clinic’s campus in Scottsdale.

The patients also undergo periodic cognitive testing, and many of them offer to participate in a bevy of different imaging studies. Based on the pioneering imaging work of Clifford Jack, M.D., in Rochester, patients may undergo magnetic resonance imaging (MRI) to examine brain structure, including changing volumes in white matter and hints of vascular damage; MR spectroscopy to assess chemical processing; functional MRI to look at the brain’s reaction to stimulus; positron emission tomography (PET) and glucose PET scanning to examine the functional aspects of performance; and the newest modality, amyloid imaging, which can provide a picture of amyloid deposition in the brain. Dr. Jack’s research has formed the basis of a $60 million, five-year grant, funded by a partnership of industry and the National Institute on Aging, to study these techniques nationwide, according to Dr. Petersen.

Through these studies, Dr. Petersen hopes doctors will be able to provide answers to those worried about developing Alzheimer’s disease — something no one has ever been able to do.

“Having a predictive equation will allow us to say, ‘You have a certain probability of developing Alzheimer’s,’” he says. “And if the probability is high, and if the therapy is risky or expensive, this information may help us determine how to intervene.”

Contact: Kevin Punsky
Mayo Clinic

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July 25, 2007 Posted by | Alberta, Alzheimers, Baltimore, Bethesda, Calgary, Canada, Global, Global Health Vision, Global News, Health Canada, Mayo Clinic, Medical Journals, Newfoundland, News, News Australia, News Canada, News Israel, News Italy, News Jerusalem, News Switzerland, News UK, News US, News USA, Nova Scotia, Ottawa, Prince Edward Island, Proteins, Public Health, Quebec, Research, RSS, RSS Feed, Toronto, UCSD, UK, University of California, US, USC, Virginia, WASHINGTON, Washington DC, Washington DC City Feed, World News | 5 Comments

Children and young people show elevated leukaemia rates near nuclear facilities

Review covers 136 countries in US, Canada, UK, France, Germany, Japan and Spain

Leukaemia rates in children and young people are elevated near nuclear facilities, but no clear explanation exists to explain the rise, according to a research review published in the July issue of European Journal of Cancer Care.

Researchers at the Medical University of South Carolina carried out a sophisticated meta-analysis of 17 research papers covering 136 nuclear sites in the UK, Canada, France, the USA, Germany, Japan and Spain.

They found that death rates for children up to the age of nine were elevated by between five and 24 per cent, depending on their proximity to nuclear facilities, and by two to 18 per cent in children and young people up to the age of 25.

Incidence rates were increased by 14 to 21 per cent in zero to nine year olds and seven to ten percent in zero to 25 year-olds.

“Childhood leukaemia is a rare disease and nuclear sites are commonly found in rural areas, which means that sample sizes tend to be small” says lead author Dr Peter J Baker.

“The advantage of carrying out a meta-analysis is that it enables us to draw together a number of studies that have employed common methods and draw wider conclusions.”

Eight separate analyses were performed – including unadjusted, random and fixed effect models – and the figures they produced showed considerable consistency.

But the authors point out that dose-response studies they looked at – which describe how an organism is affected by different levels of exposure – did not show excess rates near nuclear facilities.

“Several difficulties arise when conducting dose-response studies in an epidemiological setting as they rely on a wide range of factors that are often hard to quantify” explains Dr Baker. “It is also possible that there are environmental issues involved that we don’t yet understand.

“If the amount of exposure were too low to cause the excess risk, we would expect leukaemia rates to remain consistent before and after the start-up of a nuclear facility. However, our meta-analysis, consistently showed elevated illness and death rates for children and young people living near nuclear facilities.”

The research review looked at studies carried out between 1984 and 1999, focusing on research that provided statistics for individual sites on children and young people aged from zero to 25.

Four studies covered the UK, with a further three covering just Scotland. Three covered France, two looked at Canada and there was one study each from the USA, Japan, Spain, the former East Germany and the former West Germany.

“Although our meta-analysis found consistently elevated rates of leukaemia near nuclear facilities, it is important to note that there are still many questions to be answered, not least about why these rates increase” concludes Dr Baker.

“Several hypotheses have been proposed to explain the excess of childhood leukaemia in the vicinity of nuclear facilities, including environmental exposure and parental exposure. Professor Kinlen from Oxford University has also put forward a hypothesis that viral transmission, caused by mixing populations in a new rural location, could be responsible.

“It is clear that further research is needed into this important subject.”

Notes to editors

Meta-analysis of standardized incidence and mortality rates of childhood leukaemia in proximity to nuclear facilities. Baker PJ and Hoel D. European Journal of Cancer Care. 16, pages 355-363. July 2007.

The European Journal of Cancer Care provides a medium for communicating multi-professional cancer care across Europe and internationally. The Journal publishes peer-reviewed papers, reviews, reports, features and news, and provides a means of recording lively debate and an exchange of ideas. It is published six times a year by Blackwell Publishing.
Blackwell Publishing is the world’s leading society publisher, partnering with 665 medical, academic, and professional societies. Blackwell publishes over 800 journals and has over 6,000 books in print. The company employs over 1,000 staff members in offices in the US, UK, Australia, China, Singapore, Denmark, Germany and Japan and officially merged with John Wiley & Sons, Inc’s Scientific, Technical and Medical business in February 2007. Blackwell’s mission as an expert publisher is to create long-term partnerships with our clients that enhance learning, disseminate research, and improve the quality of professional practice. For more information on Blackwell Publishing, please visit or

Contact: Annette Whibley
Blackwell Publishing Ltd.

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July 18, 2007 Posted by | Alberta, Baltimore, Barcelona, Bethesda, Calgary, Canada, Cancer, Cancer Biology, Childhood Lukemia, European Journal of Cancer Care, France, Germany, Global, Global Health Vision, Global News, Health Canada, Japan, Leukemia, Newfoundland, News, News Australia, News Canada, News Israel, News Italy, News Jerusalem, News Switzerland, News UK, News US, News USA, Nova Scotia, Nunavut, Osaka, Ottawa, Oxford University, Pennsylvania, Prince Edward Island, Quebec, RSS, RSS Feed, Slovakia, Spain, Toronto, UK, US, Virginia, WASHINGTON, Washington DC, Washington DC City Feed, World News | Leave a comment

One man’s junk may be a genomic treasure

Scientists have only recently begun to speculate that what’s referred to as “junk” DNA – the 96 percent of the human genome that doesn’t encode for proteins and previously seemed to have no useful purpose – is present in the genome for an important reason. But it wasn’t clear what the reason was. Now, researchers at the University of California, San Diego (UCSD) School of Medicine have discovered one important function of so-called junk DNA.

Genes, which make up about four percent of the genome, encode for proteins, “the building blocks of life.” An international collaboration of scientists led by Michael G. Rosenfeld, M.D., Howard Hughes Medical Investigator and UCSD professor of medicine, found that some of the remaining 96 percent of genomic material might be important in the formation of boundaries that help properly organize these building blocks. Their work will be published in the July 13 issue of the journal Science.

“Some of the ‘junk’ DNA might be considered ‘punctuation marks’ – commas and periods that help make sense of the coding portion of the genome,” said first author Victoria Lunyak, Ph.D., assistant research scientist at UCSD.

In mice, as in humans, only about 4 percent of the genome encodes for protein function; the remainder, or “junk” DNA, represents repetitive and non-coding sequences. The research team studied a repeated genomic sequence called SINE B2, which is located on the growth hormone gene locus, the gene related to the aging process and longevity. The scientists were surprised to find that SINE B2 sequence is critical to formation of the functional domain boundaries for this locus.

Functional domains are stretches of DNA within the genome that contain all the regulatory signals and other information necessary to activate or repress a particular gene. Each domain is an entity unto itself that is defined, or bracketed, by a boundary, much as words in a sentence are bracketed by punctuation marks. The researchers’ data suggest that repeated genomic sequences might be a widely used strategy used in mammals to organize functional domains.

“Without boundary elements, the coding portion of the genome is like a long, run-on sequence of words without punctuation,” said Rosenfeld.

Decoding the information written in “junk” DNA could open new areas of medical research, particularly in the area of gene therapy. Scientists may find that transferring encoding genes into a patient, without also transferring the surrounding genomic sequences which give structure or meaning to these genes, would render gene therapy ineffective.

Contributors to the paper include Lluis Montoliu, Rosa Roy and Angel Garcia-Díaz of the Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología in Madrid, Spain; Christopher K. Glass, M.D., Ph.D., UCSD Department of Cellular and Molecular Medicine; Esperanza Núñez, Gratien G. Prefontaine, Bong-Gun Ju, Kenneth A. Ohgi, Kasey Hutt, Xiaoyan Zhu and Yun Yung, Howard Hughes Medical Institute, Department of Molecular Medicine, UCSD School of Medicine; and Thorsten Cramer, Division of Endocrinology, UCSD Department of Medicine.

The research was funded in part by the Howard Hughes Medical Institute and the National Institutes of Health.

Contact: Debra Kain
University of California – San Diego

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July 13, 2007 Posted by | Alberta, Baltimore, Barcelona, Bethesda, Biological Sciences, Calgary, Chile, DNA, Genes, Genetic, Genetics, Genome, Genomic, Global, Global Health Vision, Global News, Howard Hughes Medical Institute, Human Genome, Irvine, Italy, Japan, National Institutes of Health, Newfoundland, News, News Australia, News Canada, News Israel, News Italy, News Jerusalem, News Switzerland, News UK, News US, News USA, NIH, Nova Scotia, Osaka, Ottawa, Pennsylvania, Prince Edward Island, Proteins, Quebec, Research, Research Australia, RSS, RSS Feed, Slovakia, Spain, Toronto, UCSD, University of California, Virginia, WASHINGTON, Washington DC, Washington DC City Feed, World News | Leave a comment

Adding folic acid to flour significantly reduces congenital malformations

This release is also available in French.

Quebec City, July 12, 2007 – Dr. Philippe De Wals of Université Laval’s Department of Social and Preventive Medicine today publishes a study clearly indicating that the addition of folic acid to flours has led to a 46% drop in the incidence of congenital neural tube deformation (mainly anencephaly and spina bifida) in Canada. Such deformations either result in the child’s death or in major health problems, including physical and learning disabilities. Dr. De Wals’s work as head of a team of a dozen Canadian researchers appears today in the New England Journal of Medicine.

The neural tube is the basis of the embryo’s nervous system. Poor development of the neural tube, which is sometimes due to a lack of folic acid, can result in major health problems. Folic acid is found in green vegetables, fruit, whole grains, and meat. However, even a balanced diet won’t supply enough folic acid for a pregnant mother and the child she is carrying. Before1998, Canadian medical authorities were already recommending that women in their child-bearing years consume vitamin supplements containing folic acid. “Canada decided to add folic acid to all flour produced in the country because formation of the neural tube in embryos is particularly intense during the first four weeks of pregnancy, which is before a lot of women even know they’re pregnant. Since half of Canadian pregnancies are unplanned and the human body can’t store folic acid, it is better to integrate folic acid into the food chain than to focus exclusively on taking vitamin supplements,” stated Dr. De Wals. Health Canada still recommends taking folic acid supplements to women in their child-bearing years.

Researchers Dr. Philippe De Wals and Fassiatou Tairou of Université Laval’s Faculty of Medicine compared the incidence of neural tube deformations before and after the introduction of folic acid–enriched flours for over 2 million births in Canada. Between 1993 and 1997, the incidence was 1.58 per 1,000 births. Between 2000 and 2002, the rate dropped 46% to 0.86. The biggest improvement occurred in the parts of Canada that had the highest rates of neural tube deformation before 1998—Newfoundland, Prince Edward Island, and Nova Scotia. In Québec, the drop was also pronounced, but closer to the Canadian average.

Currently, only Canada, the United States, and Chile require that folic acid be added to flour. The effectiveness of this practice, as demonstrated by Dr. De Wals’s team, could encourage other countries to follow suit. Every year, approximately 200,000 cases of spina bifida and anencephaly occur worldwide. Adding folic acid to food could reduce that number by half.

Contact: Martin Guay
Université Laval

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July 12, 2007 Posted by | Alberta, Baltimore, Barcelona, Bethesda, Bone Diseases, Calgary, Chile, Folic Acid, Global, Global Health Vision, Global News, Health Canada, Irvine, Italy, Japan, Medical Journals, Neurology, New England Journal of Medicine, Newfoundland, News, News Australia, News Canada, News Israel, News Italy, News Jerusalem, News Switzerland, News UK, News US, News USA, Nova Scotia, Nutritional Anthropology, Osaka, Ottawa, Pennsylvania, Prince Edward Island, Quebec, Research, Research Australia, RSS, RSS Feed, Slovakia, Spain, Spina Bifida, Toronto, Université Laval, Virginia, WASHINGTON, Washington DC, Washington DC City Feed, World News | 1 Comment

Study shows an electronic medical records system can pay for itself within 16 months

CHICAGO (July 12, 2007) — A new study to be published in the July issue of the Journal of the American College of Surgeons shows that one academic medical center recouped its investment in electronic health records within 16 months. The new analysis counters concerns of health care providers reluctant to invest in electronic medical records systems.

The widespread loss of paper medical records in New Orleans after Hurricane Katrina is one of several factors behind the recent push to get surgeons and other health care providers to go electronic, according to David A. Krusch, MD, FACS, of the University of Rochester Department of Surgery and co-author of the study.

“Health care providers most frequently cite cost as primary obstacle to adopting an electronic medical records system. And, until this point, evidence supporting a positive return on investment for electronic health records technologies has been largely anecdotal,” said Dr. Krusch.

The study measured the return on investment of installing electronic health records at five ambulatory offices representing 28 providers within the University of Rochester (NY) Medical Center. Starting in November 2003, the offices implemented a Touchworks EHR system from Chicago-based Allscripts over the next five months. The study compared the cost of activities such as pulling charts, creating new charts, filing time, support staff salary, and transcription when done electronically in the third quarter of 2005, versus the cost of those same activities performed manually in the third quarter of 2003.

The University of Rochester Medical Center estimated that the new electronic medical records system reduced costs by $393,662 per year, nearly two-thirds of that coming from a sharp reduction in the time required to manually pull charts. Given that its electronic system cost $484,577 to install and operate, it took the University of Rochester Medical Center 16 months to recoup its investment. After the first year, it cost about $114,016 annually to operate the new system, which translates to a savings of $279,546 a year for the medical center, or $9,983 per provider.

The complete study, “A Pilot Study to Document the Return on Investment for Implementing an Ambulatory Electronic Health Record at an Academic Medical Center”, will appear in the July issue of the Journal of the American College of Surgeons. In addition to Krusch, Dara L. Grieger, MD, of the University of Rochester Department of Surgery and Stephen H. Cohen, MN, CPE, also co-authored the article.

The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and to improve the care of the surgical patient. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 71,000 members and it is the largest organization of surgeons in the world. For more information, visit

Contact: Sally Garneski
Weber Shandwick Worldwide

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July 12, 2007 Posted by | Alberta, Baltimore, Barcelona, Bethesda, Calgary, Electronic Health Records, Global, Global Health Vision, Global News, Historical Medicine, Irvine, Italy, Japan, Journal of the American College of Surgeons, Medical History, Medical Journals, News, News Australia, News Canada, News Israel, News Italy, News Jerusalem, News Switzerland, News UK, News US, News USA, Osaka, Ottawa, Pennsylvania, Research, Research Australia, RSS, RSS Feed, Slovakia, Spain, Toronto, University of Rochester, Virginia, WASHINGTON, Washington DC, Washington DC City Feed, World News | Leave a comment

Tobacco industry efforts to derail effective anti-smoking campaigns

Anti-smoking ads that reveal the tobacco industry’s deceptive practices have been aggressively quashed through various methods found Temple University Assistant Professor Jennifer K. Ibrahim, co-author of an analysis in the August issue of the American Journal of Public Health.

In the article, Ibrahim tracks the rise and fall of state and national efforts to curb smoking for the past 40 years. She chronicles industry strategies to prevent a campaign’s creation, steer messages to smaller audiences, limit the content of the message, limit or eliminate the campaign’s funding, and pursue litigation against the campaign. Ibrahim looks at campaigns in Minnesota, California, Arizona, Oregon, Florida, and a national campaign from the American Legacy Foundation.

This billboard was part of a weak media campaign in Michigan after Gov. John Engler’s political staff took control of the campaign, excluding the state health department’s staff from any…

“It tells the story behind the smoke. People often judge these ads and now you know what the tobacco industry was doing trying to undermine them,” Ibrahim said.

Research has found ads that reveal the deceptive practices of the tobacco industry are the most effective media campaigns that reduce smoking rates, she said.

This billboard ad from California in 2001 is considered a more effective message to reduce smoking rates.

For example, one billboard in California read “Tobacco is legal, profitable, and kills people” featuring an alligator labeled big tobacco with a smirk saying “Two out of three’s not bad.”

However, these messages aren’t always getting out there because of the money spent by the tobacco industry to eliminate them, said Ibrahim, an assistant professor of public health.

State health departments face an uphill battle when dealing with the political clout of the industry with its lobbying, campaign contributions and specials events, Ibrahim said.

One tactic also involves the industry producing its own ineffective campaigns in order to portray state programs as duplicative and a waste of public dollars. Campaigns designed by the tobacco companies patronize youth in their early teen years, with messages like “Think, Don’t smoke”, Ibrahim said.

In contrast, Florida’s “truth” anti-smoking campaign empowered them by giving them information about how the tobacco industry tried to manipulate by marketing.

The tobacco industry has spent more money in advertising in light of successful media campaigns that target large audiences.

From 1975 to 2003, tobacco industry expenditures in advertising and promotion grew from $491 million to $15.5 billion. During this period, the percentage of smokers in the United States fell from about 37 percent to 22 percent, according to the Behavioral Risk Factor Surveillance System.

Attitudes are changing as the public is becoming more aware about the dangers of smoking, secondhand smoke, and the deceptive practices of the industry, Ibrahim said.

While the numbers offer some promise, more initiatives are needed to keep anti-smoking efforts alive.

“It’s naïve to think the industry is still not following these practices and preparing tactics to respond,” Ibrahim said.

The Master Settlement Agreement in 1998 marked an important step when seven tobacco companies agreed to change the way tobacco products are marketed, release previously secret industry documents, dispand trade groups, and pay the states an estimated $206 billion. The tobacco companies also agreed to finance a $1.5 billion public anti-smoking campaign.

States’ attorney generals continue to enforce the provisions of the agreement, Ibrahim said.

A recent product that has created uproar is Camel’s No. 9s pink cigarettes that public health advocates say target teenage girls not women. In June, congress sent a letter to the editors of 11 major magazines, from Glamour to Cosmopolitan, requesting them to stop running the ads for the cigarettes.

Aggressive efforts to battle current marketing efforts and litigation from the tobacco industry are vital to keep the best media campaigns from disappearing, Ibrahim said.

“The efforts put forth by California and the American Legacy Foundation as they pursued legal battles with tobacco companies provide a good example of the tenacity needed to successfully defend and promote tobacco control campaigns,” said Ibrahim. “Persistence can pay off. We need to go with campaigns that work,”

The research was funded by the National Cancer Institute. For the article, Ibrahim collected the data, conducted the analysis, and drafted the article. Co-author Stanton A. Glantz from the Center for Tobacco Control Research and Education at the University of California, San Francisco, supervised the data collection, edited and revised the article.

Contact: Anna Nguyen
Temple University

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July 11, 2007 Posted by | Alberta, American Journal of Public Health, American Legacy Foundation, Baltimore, Barcelona, Bethesda, Calgary, Cancer, COPD, Global, Global Health Vision, Global News, Italy, Japan, Lung Cancer, Medical Journals, National Cancer Institute, News, News Australia, News Canada, News Israel, News Italy, News Jerusalem, News Switzerland, News UK, News US, News USA, Osaka, Ottawa, Pennsylvania, RSS, RSS Feed, Slovakia, Spain, Temple University, Toronto, Uncategorized, Virginia, WASHINGTON, Washington DC, Washington DC City Feed, World News | Leave a comment

Organic farming can feed the world, U-M study shows

July 10, 2007

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ANN ARBOR, Mich.—Organic farming can yield up to three times as much food as conventional farming on the same amount of land—according to new findings which refute the long-standing assumption that organic farming methods cannot produce enough food to feed the global population.

Researchers from the University of Michigan found that in developed countries, yields were almost equal on organic and conventional farms. In developing countries, food production could double or triple using organic methods, said Ivette Perfecto, professor at U-M’s School of Natural Resources and Environment, and one the study’s principal investigators. Catherine Badgley, research scientist in the Museum of Paleontology, is a co-author of the paper along with several current and former graduate and undergraduate students from U-M.

“My hope is that we can finally put a nail in the coffin of the idea that you can’t produce enough food through organic agriculture,” Perfecto said.

In addition to equal or greater yields, the authors found that those yields could be accomplished using existing quantities of organic fertilizers, and without putting more farmland into production.

The idea to undertake an exhaustive review of existing data about yields and nitrogen availability was fueled in a roundabout way, when Perfecto and Badgley were teaching a class about the global food system and visiting farms in Southern Michigan.

“We were struck by how much food the organic farmers would produce,” Perfecto said. The researchers set about compiling data from published literature to investigate the two chief objections to organic farming: low yields and lack of organically acceptable nitrogen sources.

Their findings refute those key arguments, Perfecto said, and confirm that organic farming is less environmentally harmful yet can potentially produce more than enough food. This is especially good news for developing countries, where it’s sometimes impossible to deliver food from outside, so farmers must supply their own. Yields in developing countries could increase dramatically by switching to organic farming, Perfecto said.

While that seems counterintuitive, it makes sense because in developing countries, many farmers still do not have the access to the expensive fertilizers and pesticides that farmers use in developed countries to produce those high yields, she said.

After comparing yields of organic and convention farms, the researchers looked at nitrogen availability. To do so, they multiplied the current farm land area by the average amount of nitrogen available for production crops if so-called “green manures” were planted between growing seasons. Green manures are cover crops which are plowed into the soil to provide natural soil amendments instead of synthetic fertilizers. They found that planting green manures between growing seasons provided enough nitrogen to farm organically without synthetic fertilizers.

Organic farming is important because conventional agriculture—which involves high-yielding plants, mechanized tillage, synthetic fertilizers and biocides—is so detrimental to the environment, Perfecto said. For instance, fertilizer runoff from conventional agriculture is the chief culprit in creating dead zones—low oxygen areas where marine life cannot survive. Proponents of organic farming argue that conventional farming also causes soil erosion, greenhouse gas emission, increased pest resistance and loss of biodiversity.

For their analysis, researchers defined the term organic as: practices referred to as sustainable or ecological; that utilize non-synthetic nutrient cycling processes; that exclude or rarely use synthetic pesticides; and sustain or regenerate the soil quality.

Perfecto said the idea that people would go hungry if farming went organic is “ridiculous.”

“Corporate interest in agriculture and the way agriculture research has been conducted in land grant institutions, with a lot of influence by the chemical companies and pesticide companies as well as fertilizer companies—all have been playing an important role in convincing the public that you need to have these inputs to produce food,” she said.

Contact: Laura Bailey
Phone: (734) 647-1848

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New gene mutation identified in common type of dementia

ST. PAUL, MN — Researchers have identified a new gene mutation linked to frontotemporal dementia, according to a study published in the July 10, 2007 issue of Neurology®, the medical journal of the American Academy of Neurology.

Frontotemporal dementia, one form of which is known as Pick’s disease, involves progressive shrinking of the areas of the brain that control behavior and language. Symptoms include language problems and personality changes, often with inappropriate social behavior. Unlike Alzheimer’s disease dementia, the disease does not affect memory in the early stages. The genetic form of the disease is rare; most cases occur randomly.

“We are hopeful that this finding will help us better understand how this disease works and eventually help us develop new therapies for the disease,” said study author Amalia Bruni, MD, of the Regional Neurogenetic Centre in Lamezia Terme, Italy.

The researchers discovered a new mutation in the gene named progranulin in an extended family in southern Italy. The genealogy of this family has been reconstructed for 15 generations, going back to the 16th century; 36 family members have had frontotemporal dementia. For this study, DNA tests were conducted on 70 family members, including 13 people with the disease. “This is an important result that we pursued for more than 10 years,” said study co-author Ekaterina Rogaeva, PhD, with the Centre for Research in Neurodegenerative Diseases at the University of Toronto.

The mutation identified in this study is in a gene on chromosome 17. The mutation leads to a loss of progranulin, a protein growth factor that helps brain cells survive. The mutation causes only half of the protein to be produced, because only one copy of the gene is active. Production of too much progranulin has been associated with cancer.

The new gene mutation was found in nine of those family members with the disease and 10 people who are currently too young to have the symptoms of the disease. But four people with the disease did not have the gene mutation. Bruni noted that these four people belong to a branch of the family with the disease in at least three generations. “These results are intriguing, since the family has two genetically distinct diseases that appear almost identical,” said Bruni.

The Italian family had no cases with two copies of the mutated gene. “We would have expected to see cases with two copies of the mutated gene, especially since this family shares much of the same genetic material, as there have been at least five marriages between first cousins over the years,” Bruni said. “It’s possible that loss of both copies of the progranulin gene leads to the death of embryos, and that’s why there were no cases with two copies of the mutated gene.”

“Another intriguing aspect in this Italian family is the variable age at onset, which ranged from 35 to 87 years in the family members who inherited the same mutation. Our future research will try to identify the modifying factors responsible for the severity of the disorder,” said Rogaeva.

Rogaeva says their studies will also try to identify the second gene responsible for dementia in this family.

The study was supported by grants from the Canadian Institutes of Health Research, Howard Hughes Medical Institute, Canada Foundation for Innovation, Japan-Canada and Canadian Institutes of Health Research Joint Health Research Program, Parkinson Society of Canada, W. Garfield Weston Fellows, Japanese Society for the Promotion of Science, National Institute on Aging Intramural Program, Italian Ministry of Health, and the Calabria Regional Health Department.

The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer’s disease, epilepsy, Parkinson’s disease, and multiple sclerosis.

For more information about the American Academy of Neurology, visit


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July 10, 2007 Posted by | Alberta, Alzheimers, Baltimore, Barcelona, Bethesda, Calabria Regional Health Department, Calgary, Canadian Institutes of Health Research, Cancer, Chromosome 17, Epilepsy, Genes, Genetic, Genetic Link, Genetics, Global, Global Health Vision, Global News, Howard Hughes Medical Institute, Italy, Japanese Society for the Promotion of Science, Joint Health Research Program, Lamezia Terme, Multiple Sclerosis, Neurodegenerative Diseases, News, News Australia, News Canada, News Israel, News Italy, News Jerusalem, News Switzerland, News UK, News US, News USA, Ottawa, Parkinson Society of Canada, Parkinson's, Pick's Disease, Progranulin, Protein Growth Factor, Research, RSS, RSS Feed, Stroke, The American Academy of Neurology, Toronto, University of Toronto, Virginia, W. Garfield Weston Fellows, WASHINGTON, Washington DC, Washington DC City Feed, World News | Leave a comment