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Epileptic Seizures May Lead to Reduced Medication Entry to the Brain, Say Researchers

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Researchers have found that one of the body’s own neurotransmitters released during epileptic seizures, glutamate, could lead to reduced medication entry into the brain. This may explain why approximately 30% of patients with epilepsy do not respond to anti-epileptic medications.

The study was conducted by researchers at the National Institute of Environmental Health Sciences (NIEHS) using a rodent model of epilepsy.

"Our work identifies the mechanism by which seizures increase production of a drug transport protein in the blood brain barrier, known as P-glycoprotein, and suggests new therapeutic targets that could reduce resistance," said David Miller, Ph.D., a principal investigator in the NIEHS Laboratory of Pharmacology and co-author on the paper.

The blood-brain barrier (BBB), which resides in brain capillaries, is a limiting factor in treatment of many central nervous system disorders. It is altered in epilepsy so that it no longer permits free passage of administered antiepileptic drugs into the brain. Miller explained that P-glycoprotein forms a functional barrier in the BBB that protects the brain by limiting access of foreign chemicals.

"The problem is that the protein does not distinguish well between neurotoxicants and therapeutic drugs, so it can often be an obstacle to the treatment of a number of diseases, including brain cancer," Miller said. Increased levels of P-glycoprotein in the BBB has been suggested as one probable cause of drug resistance in epilepsy.

Using isolated brain capillaries from mice and rats and an animal model of epilepsy, the researchers found that glutamate, a neurotransmitter released when neurons fire during seizures, turns on a signaling pathway that activates cyclooxygenase-2 (COX-2), causing increased synthesis of P-glycoprotein in these experiments. Increased transporter expression was abolished in COX-2 knockout mice or by COX-2 inhibitors. It has yet to be shown in animals or patients that targeting COX-2 will reduce seizure frequency or increase the effectiveness of anti-epileptic drugs.

"These findings provide insight into one mechanism that underlies drug resistance in epilepsy and possibly other central nervous system disorders," said Bjoern Bauer, Ph.D., lead author on the publication. "Targeting blood-brain barrier signals that increase P-glycoprotein expression rather than the transporter itself suggests a promising way to improve the effectiveness of drugs that are used to treat epilepsy, though more research is needed before new therapies can be developed."

The study appears in the May, 2008 issue of Molecular Pharmacology.

Malaria Protection Provided By Inherited Blood Disorder

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An inherited childrens’ blood disorder called alpha thalassemia can protect children against malaria, according to a new study.

"We made the surprising finding that packaging your hemoglobin in smaller amounts in more cells is an advantage against malaria," says Karen Day, Ph.D., Professor and Chairman of the Department of Medical Parasitology at NYU School of Medicine, who led the research with colleagues at the University of Oxford. Hemoglobin is the oxygen-carrying protein in red blood cells.The study, published in the March issue of the journal PLoS Medicine, proposes an answer to a biological puzzle that first emerged more than 50 years ago.

The study was conducted in Papua, New Guinea, where malaria is endemic, with 800 children participating. 68% of children there have alpha thalassemia. Dr. Day and her then-Ph D. student Freya J.I. Fowkes, and colleagues from the University of Oxford, Papua New Guinea Institute of Medical Research, and Swansea University showed that a severe attack of malaria caused the loss of one third to one half of the total number of red blood cells. However, children with mild thalassemia started with 10% –20% more red blood cells than unaffected children, and could therefore withstand this huge loss.

"It is really remarkable and so simple. Children with alpha thalassemia have adapted to the loss of red blood cells associated with malarial disease by making more of these cells with less hemoglobin," says Dr. Day. "So, these children do better because they end up with more hemoglobin overall when they have a malaria attack compared to normal children," says Dr. Day.
Malaria afflicts hundreds of millions of people, causing up to 2 million deaths every year in Africa and Asia. Many of its victims are young children. In regions of the world where malaria is endemic, mutations have arisen in human populations that allow people to survive. Sickle cell trait, for example, protects against malaria.

Nearly sixty years ago the renowned evolutionary biologist J.B.S.Haldane postulated that the thalassemias were common in human populations because they protected against malaria. Alpha thalassemia is common in Asia, the Mediterranean and Melanesia where malaria is or was prevalent. In the mid 1990s researchers working on the north coast of Papua New Guinea proved that children with mild alpha thalassemia, who inherit mutations in the "alpha" part of hemoglobin genes from each parent, were protected against malaria. These children were 60 percent less likely to get severe malarial anemia than normal children, however the mechanism of such protection was unclear.

Dr. Day and colleagues based their new study on this same population of children. "We are proposing an unexpected mechanism of protection against severe malarial anemia" says Dr. Day. "We show that alpha thalassemia is giving the child a hematological advantage by making more red blood cells.

Source: New York University Medical Center

TV in Teens’ Bedrooms Promotes Poor Diet and Exercise Routines

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University of Minnesota School of Public Health researchers have found that a television in the bedroom promotes poor dietary, study and exercise habits among teenagers. 62% of a sample of 781 teenagers aged 15 to 18 in the Minneapolis area had a television in their bedroom, and spent 4 to 5 hours per week watching television. Bedroom TV owners ranked as heavy watchers, at least 5 hours a day—twice the amount of teenagers without one.

Boys among the television owners achieved a lower grade point average, had less fruit and ate fewer meals with the family than boys without one. Girls owning television sets spent only 1.8 hours per week exercising (versus 2.5 hours for girls without one), consumer less vegetables, ate fewer family meals and drank more sweetened soft drinks.

Daheia Barr-Anderson, one of the research team, was quoted as saying that these results showed that there were clear advantages to banning a TV from a teenager’s bedroom. This view was supported by the American Academy of Pediatrics, which encouraged the removal of TV sets by parents from their childrens’ bedrooms. The findings of the study were published in the Academy’s journal, Pediatrics.

Statistically, the study showed that 68% of boys, compared with 58% of girls, would probably have a bedroom TV, while children from the highest income families were less likely to have one. 82% of black teenagers had a television in their bedroom, while only 66% of Hispanic teens and 60% of whites had one. 39% of Asian American teens reported ownership.

In this study, body mass index was not found to influence teenage obesity, although Barr-Andersen quoted previous studies that showed that ownership of a bedroom TV was a strong predictor of obesity. Both boys and girls with bedroom TV’s admitted to devoting less time to reading and homework, although the differences were not statistically significant, said the researchers.

New Procedures Save Frostbite Victims from Amputation

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The standard treatment for frostbite has not changed in decades—re-warming the affected areas, with amputation in severe cases. Radiologists can now re-open recently frozen, clotted arteries with clot-busting and anti-spasmodic drugs, using imaging to visualize areas lacking blood flow and deliver drugs via catheter.

With severely frostbitten hands and feet, subjects in a recent test would typically lose their limbs to gangrene. In this case, Angiography, an X-ray exam of the arteries and veins, was used by interventional radiologists to verify loss of blood flow to a patient’s hand or toes. Intra-arterial catheters then supplied drugs to dissolve the blood clots and relax the arteries’ muscular walls.

A study released today at the Society of Interventional Radiology’s 33rd Annual Scientific Meeting confirmed that this treatment was significantly successful in preventing amputation and saving limbs.

"Previously severe frostbite was a one-way route to limb loss. This treatment is a significant improvement. We’re opening arteries that are blocked so that tissues can heal and limbs can be salvaged. We were able to reopen even the smallest arteries, saving patients’ fingers and toes," said George R. Edmonson, M.D., interventional radiologist with St. Paul Radiology in St. Paul, Minnesota.

According to Edmonson, severe frostbite or "freezeburn" looks like a second degree heat burn with large blisters, but it’s actually body tissue that’s been frozen and-in severe cases-dead, he said. "For half our patients who received the clot-busting drug Tenectaplase, this technique worked beautifully, saving all fingers, hands, toes and feet that otherwise would have been lost," said Edmonson, who has been treating an average of 6–10 frostbite patients each year for the past 10 years.

"Overall, in about 80 percent of the cases, it significantly improved patients’ outcomes. Within one to three days of treatment, we saw improvement," noted Edmonson, explaining that patients were followed for six weeks to assess their final outcomes.

Source: Society for Interventional Radiology

Alcohol May Cause Lower Brain Volume

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According to a recent report, the more you drink the smaller your brain becomes. It is estimated that 1.9 percent decrease in brain volume per decade accompanies an increase in white matter lesions.

The progression of dementia and problems with thinking, learning and memory are accompanied by lower brain volumes and larger white matter lesions. Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease; because the brain receives blood from this system, researchers have hypothesized that small amounts of alcohol may also attenuate age-related declines in brain volume. The study results were published in the October, 2008 issue of Archives of Neurology.

Members of the Framingham Offspring Study, which began in 1971 and included 1,839 adults with an average age of 60, were studied by Carol Ann Paul, M.S., of Wellesley College, Mass., and colleagues. The Study also included children of the original Framingham Heart Study participants and their spouses. Between 1999 and 2001, participants underwent magnetic resonance imaging (MRI) and a health examination. They reported the number of alcoholic drinks they consumed per week, along with their age, sex, education, height, body mass index and Framingham Stroke Risk Profile (which calculates stroke risk based on age, sex, blood pressure and other factors).

“Most participants reported low alcohol consumption, and men were more likely than women to be moderate or heavy drinkers,” the authors write. “There was a significant negative linear relationship between alcohol consumption and total cerebral brain volume.”

Although men were more likely to drink alcohol, the association between drinking and brain volume was stronger in women, they note. This could be due to biological factors, including women’s smaller size and greater susceptibility to alcohol’s effects.

“The public health effect of this study gives a clear message about the possible dangers of drinking alcohol,” the authors write. “Prospective longitudinal studies are needed to confirm these results as well as to determine whether there are any functional consequences associated with increasing alcohol consumption. This study suggests that, unlike the associations with cardiovascular disease, alcohol consumption does not have any protective effect on brain volume.”

Source: Archives of Neurology,

Protecting Yourself from the Sun to Avoid Skin Cancer

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Before leaving home for a day of outdoor activity, take appropriate precautions to ensure that your and your family’s skin is well-protected, as the majority of all skin cancers are caused by the sun.

According to Susan Chon, M.D., assistant professor of dermatology at The University of Texas M. D. Anderson Cancer Center, a sunscreen with an SPF of at least 30 is a good choice for most people. One ounce of sunscreen (enough to fill a shot glass) is considered sufficient to properly cover sun-exposed areas. To get the most protection from sunscreen, generously reapply throughout the day. This is especially important because factors such as humidity, perspiration and uneven product application can cause sunscreen to lose its effectiveness.

Sun Protection Checklist
Chon recommends gathering the following items before heading outdoors.

  • Sunscreen with SPF 30 or greater
  • Lip balm with SPF 30
  • Hat with a brim or cap
  • Long-sleeved shirt (preferably sun protective clothing)
  • Sunglasses with UV protection

"These are great items to keep handy in your bag to prepare for the sun as it intensifies throughout the day," Chon said.

Application Time Line
Chon suggests the following time line for when to best use these items.

Morning: 8 – 10 a.m. Apply sunscreen with SPF 30, at least 30 minutes before sun exposure.
Reapply sunscreen every two hours.
Wear a hat, sunglasses and lip balm.

Midday: 11 a.m. – 2 p.m. (hottest time of the day)
Seek shade for extra protection.
Wear a long-sleeved shirt with a hat and sunglasses.
Reapply sunscreen and lip balm every two hours.

Afternoon: 3 – 5 p.m.
Keep wearing a hat and sunglasses.
Reapply sunscreen and lip balm every two hours.

"Remember, if you are sweating or swimming, you may need to reapply more often," Chon said. Avoid reflective surfaces such as water, sand, snow and concrete. "You can burn from indirect exposure to the sun, too," Chon said.

According to the American Cancer Society, more than one million cases of basal cell or squamous cell cancers, the most common types of skin cancer, occur annually. The most serious form of skin cancer is melanoma, of which more than 60,000 people are expected to be diagnosed in 2008.

Source: University of Texas M. D. Anderson Cancer Center

Brain Changes in Elderly Can Affect Mobility and Balance

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Changes in the brain can affect old people’s mobility and balance, according to a recent study. Particularly affecting balance and walking are white matter changes called leukoaraiosis.

The 639 men and women between the ages of 65 and 84 in the study underwent brain scans and walking and balance tests. 284 people in the group had mild age-related white matter changes, 197 moderate changes, and 158 severe changes.

People with severe white matter changes were twice as likely to score poorly on the walking and balance tests as people with mild white matter changes, the study found. The people with severe changes were also twice as likely as those with mild changes to have a history of falls. The moderate group was only one and a half times as likely as the mild group to have a history of falls.

"Walking difficulties and falls are major symptoms of people with white matter changes and a significant cause of illness and death in the elderly," said study author Hansjoerg Baezner, MD, PhD, with the University of Heidelberg in Mannheim, Germany. "Exercise may have the potential to reduce the risk of these problems since exercise is associated with improved walking and balance. We’ll be testing whether exercise has such a protective effect in our long-term study of this group."

"Mobility is one of the key determinants of independent aging," said Baezner. "Limitations in mobility often lead to hospitalization and nursing home placement. This will become a major problem for our social and economic systems in the upcoming decades."

Published in Neurology, the medical journal of the American Academy of Neurology,the 3-year study was coordinated by the Department of Neurological and Psychiatric Sciences of the University of Florence.

Source: Neurology, March 18, 2008

Genistein in Soybeans May Halt Prostate Cancer Spread

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Genistein, an antioxidant found in soybeans, almost completely prevented the spread of human prostate cancer in mice, according to a study published in the journal Cancer Research. In the study, genistein was used in an amount equivalent to what a human being would consume in a soybean-rich diet.

Genistein decreased metastasis of prostate cancer to the lungs by 96% compared with mice that did not eat the compound, the first demonstration that genistein can stop prostate cancer metastasis in a living organism. "These impressive results give us hope that genistein might show some effect in preventing the spread of prostate cancer in patients," said the study’s senior investigator, Raymond C. Bergan, MD, director of experimental therapeutics for the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

"Diet can affect cancer and it doesn’t do it by magic," Bergan said. "Certain chemicals have beneficial effects and now we have all the preclinical studies we need to suggest genistein might be a very promising chemopreventive drug."

Bergan has already shown in prostate cell cultures that genistein slows detachment of cancer cells from a primary prostate tumor, and checks cell invasion. It does this by blocking activation of p38 MAP kinases, molecules which regulate pathways that activate proteins that loosen cancer cells from their tight hold within a tumor, pushing them to migrate. "In culture, you can actually see that when genistein is introduced, cells flatten themselves in order to spread out and stick strongly to nearby cells," he said.

Researchers implanted groups of mice with an aggressive form of prostate cancer, having first fed them genistein. The amount of the chemical in the mouses’ blood was equivalent to human blood concentrations after eating soy foods, said Bergan. Genistein stopped lung mestasis almost completely, although it did not reduce the size of the tumors that developed within the prostate. Repeating the experiment produced he same result.

The size of tumor cells’ nuclei in the animals’ tissue was checked, to see whether he cells had flattened t in rder to spread. "Within a tumor, it is hard to tell where the borders of cells stop, so one way to measure adherence is to look at the size of the nuclei in cells and see if they are wider due to cell spread," Bergan said. "And that is what we found, demonstrating that the drug is having a primary effect on metastasis."

"What we think is happening here is that the cells we put in the mice normally like to move. When genistein restricted their ability to do so, they tried to compensate by producing more protein involved in migration. But genistein prevented those proteins from being activated," he said. "This is really a lesson for researchers who depend on biomarker studies to test whether a treatment is working. They need to be aware that those biomarkers might be telling only half of the story."

Source: Cancer Research, a journal of the American Association for Cancer Research. March 15, 2008.

Ayuverdic Natural Medicine Balances Health And Life

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Comprising yoga, massage, meditation and much more, Ayuverdic medicine is among the world’s oldest, and reputedly balances life and health. It originated in India more than 5,000 years ago, and is still practiced there alongside Western medicine.

Ayuverdic medicine is based on the belief that balance in life starts at birth, where a person’s innate qualities help to frame the person’s physical and mental patterns, to create the state known as praktiki. A person’s present state is known as vikruti, which is praktiki incorporating everything affecting one’s life—work, diet, hobbies and friends, for example. The closer one is to praktiki the better. Discord in life, or divergence from self, leads to dosha imbalance. Dosha refers to energy patterns.

To identify diseases, practitioners of ayurvedic medicine must evaluate what dosha is the greatest influence in the patient and seek to understand if there’s discourse between the innate and current self. Individuals can apply ayurvedic medicine to everyday situations, too. For example, dry skin may require more than lotion. One may need to look at emotions and consider how to heal emotional dryness.

An overview of ayuverdic medicine is published in the March, 2008 issue of Mayo Clinic Health Letter.

Not Enough Doctors to Treat Increasing Number of Obese and Diabetic Children

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The number of diabetic and obese children is growing so rapidly that there aren’t enough doctors to treat the kids. According to a recent study by University of Michigan’s C.S. Mott Hospital, there is only one board-certified pediatric endocrinologist per 290 children with diabetes. The ratio of obese children to board-certified endocrinologists is 17,000 to 1. The rate if childhood obesity in the United States meanwhile has more than doubled in the past 20 years, with a corresponding increase in the number of children at risk for type 1and type 2 diabetes.

"Although the American Diabetes Association recommends that all children with diabetes be cared for by a pediatric endocrinologist as part of a diabetes team, there is a current shortage of pediatric endocrinologists in this country," says study lead author Joyce Lee, M.D., MPH, a pediatric endocrinologist and member of the Child Health Evaluation and Research (CHEAR) Unit in the U-M Division of General Pediatrics. "This problem will likely only worsen due to the recent epidemic of childhood obesity."

The 16.5% of American children aged 6 to 19 who are obese are at risk for ‘adult’ diseases such as type 2 diabetes, elevated blood pressure and high cholesterol. As a result more children than ever are being referred to pediatric endocrinologists for screening, evaluation and management. "But even if just a small fraction of obese children are referred to a pediatric endocrinologist for evaluation", says Lee, " the overall ratio of one pediatric endocrinologist to 17,000 obese children makes providing the necessary care extremely challenging." Dr. Lee is assistant professor in the Department of Pediatrics and Communicable Diseases at the U-M Medical School.

Available pediatric endocrinologists are so few in relation to the number of children at risk that they cannot see even a fraction of the children with diabetes or at risk for the disease. "The epidemic of childhood obesity has undoubtedly created new challenges for our health care, and we need to reassess the current system to ensure children with diabetes or at risk for diabetes receive appropriate care," Lee notes.

Pediatric endocrinologists currently do not have the capabilities to see even a fraction of the large number of children with diabetes or at risk for diabetes. "The epidemic of childhood obesity has undoubtedly created new challenges for our health care, and we need to reassess the current system to ensure children with diabetes or at risk for diabetes receive appropriate care," Lee notes.

Using data from the American Board of Pediatrics and the National Survey of Children’s Health, Lee and her colleagues compared the number of board certified pediatric endocrinologists by region to obese children and children with diabetes in those same areas.

Their research revealed that there are an estimated 229,249 children with diabetes, and only 790 board-certified pediatric endocrinologists in the country. And, in two states—Montana and Wyoming—there are no board-certified pediatric endocrinologists.

The study was published in the March, 2008 issue of The Journal of Pediatrics.