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Research Team Discovers Gene-Silencing Technology

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Genes that can cause certain diseases can be silenced by a new technology that could help prevent disease where gene dysfunction is involved. The research was led by Ming-Ming Zhou, Ph.D., Professor and Chairman of the Department of Structural and Chemical Biology at Mount Sinai School of Medicine.

“By being able to silence certain genes, we may be able to suppress genes that can cause diseases such as HIV/AIDS, cancer, inflammation and diseases of the central and peripheral nervous systems. We now know we can focus on these genes and potentially change the ultimate course of many diseases that have a major impact on people’s lives,” says Dr. Zhou.

Dr. Zhou, Shiraz Mujtaba, Ph.D., Assistant Professor of Structural and Chemical Biology at Mount Sinai and their colleagues found that Paramecium bursaria chlorella virus uses a viral protein to modify host DNA packing chromatin and switch host transcription machinery for viral replication. Using this information, the doctors developed a new technology capable of suppressing transcriptional expression of targeted genes in human cells, including genes that are linked to the onset of a number of diseases.

Source: Nature Cell Biology, September, 2008

Health Benefits of Dark Chocolate

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Flavonoids in dark chocolate are a naturally occurring antioxidant similar to those found in teas, red wine, and some fruits and vegetables. These flavonoids are thought to have a beneficial effect on the cardiovascular system, and one recent study showed that 6 grams of dark chocolate a day (about one square) lowered systolic and diastolic blood pressure by 2 points each.

The study also claims that dark chocolate may lower low-density lipoprotein (LDL) cholesterol levels by about 5 points. Not a major effect to be sure, but pushing the “bad” cholesterol downwards. Flavonoids also benefit how the lining of the blood vessels function.

“We think a lot of bad things that happen to the cardiovascular system are because the lining of the vessels cracks and becomes inflamed, setting the stage for plaques to form and rupture,” says Robert Sheeler, M.D., a family physician at Mayo Clinic.

Don’t forget, chocolate contains calories and fat, so these findings are not an invitation to go on chocolate binge. Dr. Sheeler says just one square a day (about 30 calories) will provide the health benefits described. He recommends chocolate that contains at least 60% cocoa; milk chocolate by contrast has only 15-25% cocoa, while dark chocolate can contain as much as 80%+ cocoa.

Source: Women’s HealthSource, Mayo Clinic , August, 2008

First Ever U.S. DuraHeart Patient Doing Well

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The DuraHeart, a new experimental, hi-tech heart-assist device, was implanted in Anthony Shannon July 30—a procedure which made history. A week later, the 62-year old Shannon was reported doing well after the operation performed by a team led by surgeon Francis Pagani, M.D., Ph.D. at the University of Michigan Cardiovascular Center. Shannon is the former director of homeland security and emergency management for Wayne County, Mich., and holds a Ph.D, in public administration.

The “maglev” or magnetic levitation technology used means that that a crucial, constantly revolving part within the hockey puck-sized implanted device never touches the walls of the pumping chamber. Instead, it levitates in the middle, suspended in a magnetic field and pushing blood along. The battery-powered device pushes blood from the heart to the body, taking over most of the function of the left side of a severely weakened heart. The advantage of this technology is that the risk of allowing blood clots to form is reduced, as is damage to blood cells, compared with devices using mechanical pumps. DuraHeart has been used for 70 European patients, and received commercial use approval after a 20-07 clinical trial.

A clinical trial for DuraHeart is being conducted by Drs. Pagani and Yoshifumi Naka, M.D.,Ph.D., from Columbia Presbyterian Hospital in New York, and heart failure patients at U-M and other U.S. centers will be invited to volunteer for it.

“The DuraHeart gives us a new, third-generation option for patients with advanced heart failure who need help to allow them to survive until they can receive a heart transplant,” says Pagani, who leads the U-M Center for Circulatory Support. He has led other national clinical trials of heart-assist devices, including the HeartMate II, which in April received approval from the U.S. Food and Drug Administration after a clinical trial. U-M now offers heart failure patients nearly a dozen different options to support their heart function, including heart transplants. U-M is the national training center for the trial, which is funded by Terumo Heart, and teams from Columbia and the University of Louisville have already traveled to Ann Arbor to learn how to implant the device.

“This trial will test the DuraHeart’s potential to overcome some of the issues that have been seen with other devices, including hemolysis caused by shear stress on red blood cells, and clotting risk caused by blood that does not circulate rapidly enough from all areas of the chamber,” Pagani explains. “It also remains to be seen if this device offers superior durability, which might make it useful as a destination therapy that could remove the need for a heart transplant.”

Some 5.3 Americans currently experience heart failure, and at any given time some 4,000 are on a waiting list for heart transplants. Because there is a shortage of suitable organ donors however, only 2,100 people in the U.S. receive new hearts, and hundreds of people die each year while waiting for a new heart. Most of the devices developed to help the heart pump over the past 20 years have been left-ventricular assist systems, known as LVADs or LVASs; others have assisted the right side or both, and all are known as VADs. Hospitals can apply for accreditation as a certified VAD center, and U-M recently became one ofmthe few such centers in the U.S.

The DuraHeart was invented and developed by a team led by Chisato Nojiri, M.D., Ph.D., the chief executive officer of Terumo Heart. More than a decade of research and development has led to this clinical trial and the trial in Europe, as well as a trial in Japan that may begin later this year. Pagani serves as an unpaid consultant to Terumo Heart.

To implant a DuraHeart device, the surgeon diverts blood flow from the ailing left ventricle of the heart into a titanium tube that leads into the pumping chamber. The magnetically levitating impeller, a flat magnetic disc, acts as a paddlewheel, turning constantly as it is magnetically attracted to the turning motor within the pump housing. This pushes blood into a flexible artificial blood vessel, which is connected to the large blood vessel called the ascending aorta.

By assisting the weak left ventricle, which is the heart chamber most commonly affected by heart failure, the DuraHeart allows the heart muscle to rest. It also provides better blood flow to the body, brain and organs than a weak heart ever could – which helps patients prepare for the arduous surgery of a heart transplant.

The DuraHeart is made by Terumo Heart, Inc. based in Ann Arbor, Michigan.

Source: University of Michigan, August, 2008

Eating Fish May Avert Memory Loss

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The risk of cognitive decline and stroke in older adults may be reduced by eating tuna and other kinds of fish, according to study by researchers in Finland.

The study used a sample of 3,660 men and women aged 65 or older and subjected them to brain scans to look for silent brain infarcts, stroke or dementia. 5 years later, 2,313 members of the sample were tested again with scans, and all participants were given questionnaires on fish in their diets.

Findings of the study showed that participants who ate broiled or baked tuna or other fish high in omega-3 fatty acids (DHA and EPA) three or more times a week were at a 26% lower risk of experiencing the silent brain lesions that cause dementia and stroke than people who were not regular fish eaters. Even one fish meal weekly reduced the risk by 13%, and the study found that regular consumption of these types of fish reduced the changes of white matter in the brains of fish eaters.

“While eating tuna and other types of fish seems to help protect against memory loss and stroke, these results were not found in people who regularly ate fried fish,” said Jyrki Virtanen, PhD, RD, with the University of Kuopio in Finland. “More research is needed as to why these types of fish may have protective effects, but the omega-3 fatty acids EPA and DHA would seem to have a major role.” Types of fish that contain high levels of DHA and EPA nutrients include salmon, mackerel, herring, sardines, and anchovies.

“Previous findings have shown that fish and fish oil can help prevent stroke, but this is one of the only studies that looks at fish’s effect on silent brain infarcts in healthy, older people,” said Virtanen. Research shows that silent brain infarcts, which are only detected by brain scans, are found in about 20 percent of otherwise healthy elderly people.

Source: Neurology, August 5, 2008

Stay Healthy in Hot Weather

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Some 200 people in the US die each summer from health problems caused by hot weather, and this number is doubled when the summer is exceptionally hot. Here are three major hot weather threats that can be moderated, or avoided completely.

Heat cramps warn of dehydration and muscular deprivation of needed oxygen. The problem can be solved by drinking cool water, stretching, and light massage of the affected areas.

Heat Exhaustion is apparent when the body temperature is seriously elevated, often above 103 degrees F, and weakness, lethargy, loss of concentration, headache and nausea follow. Judgement can be affected, and the solution is to choose a cool spot, take of excess clothing, drink cool fluids, and apply any available ice packs.

Heat stroke can affect older people who stay at home without air-conditioning. Other victims include men who exercise during hot weather. Weakness and confusion can create delirium, stupor, coma and seizures, so heat stroke should be recognized as a real medical emergency, where survival depends on immediate treatment in a hospital.

Try the following to avoid hot weather health problems:

  • Hydrate: drink 10-12 cups of water daily, more if exercise is involved
  • Stay cool: move into a room with a fan or air-conditioning
  • Stay out of the sun, particularly midday sun, and wear light, loose-fitting clothes
  • Avoid exercising in hot or humid conditions

Source: Harvard Men’s Health Watch, August, 2008

Traveler’s Diarrhea Vaccine Shows Promise

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Each year between 20%-50% of international travelers—about 10 million people— develop diarrhea. The onset of “Traveler’s Diarrhea” (TD) usually occurs within the first week of travel but may occur at any time while traveling, and even after returning home. In a recent study by researchers at The University of Texas School of Public Health, a new patch-based travelers’ diarrhea vaccine has been found to provide significant relief from diarrhea. The study results were published in a recent edition of the Lancet.

In the study, 170 travelers to Mexico and Guatemala were monitored. Of 59 individuals receiving the vaccine, only 3 suffered from severe or moderate diarrhea, while close to 24 people who took the placebo suffered from moderate or severe diarrhea.

“These results suggest that the Iomai patch has the potential to fundamentally change the way we approach prevention of this disease, an ailment against which we now have very few weapons,” said Herbert L. DuPont, M.D., professor and director of the Center for Infectious Diseases at The University of Texas School of Public Health and the principal investigator of the trial. “If these results are replicated, the Iomai vaccine will have the potential to not only mitigate a disease that sickens millions each year but also keep some patients from going on to develop the chronic symptoms of irritable bowel syndrome.”

The Trek Study was done in collaboration with UT Houston, the Johns Hopkins Bloomberg School of Public Health and other institutions. Two doses of the vaccine patch or a placebo were given to each volunteer, 2 to 3 weeks apart. The last dose was given a week before travel.

Detailed diaries were kept by travelers, with in-country checkups. The study was designed to evaluate the safety of the vaccine and the incidence of enterotoxigenic E. coli (ETEC) bacteria—the most common cause of travelers’ diarrhea. No vaccine-related serious side effects were reported. Of the few vaccinated patients who became sick, the diarrhea lasted only half a day on average, while those in the placebo group endured two days of illness and more than twice as many loose stools. Although not statistically significant, the frequency of new-onset irritable bowel syndrome, a long-term consequence of travelers’ diarrhea, was three times greater in placebo than vaccine recipients.

Approximately 55 million travelers are expected to visit countries where bacteria causing diarrhea are endemic, notably Africa, Asia and Latin America, and of these it is anticipated that 20 million will contract diarrhea. Apart from abdominal cramps and dehydration, travelers are also at higher risk of developing irritable bowel syndrome. Children are at special risk in the developing world, where diarrhea linked to enterotoxigenic E sickens 210 million children, killing an estimated 380,000 of them each year.

“Bacterial diarrheal disease is a significant medical problem both for children and travelers, and our technology represents both an advance in vaccine delivery and a breakthrough in the field of infectious disease,” said Gregory Glenn, M.D., Iomai’s chief scientific officer. “We look forward to targeting both the significant travelers’ market and developing the vaccine for the children in the developing world who still suffer serious morbidity and mortality from this disease.”

Researchers at The University of Texas School of Public Health studied the patch-based vacine as part of the Phase 2 study in conjunctoin with the Iomai Corporation. Iomai plans to initiate a Phase 3 program for the needle-free vaccine patch vaccine in 2009. If approved, the Iomai vaccine would be the first vaccine for travelers’ diarrhea available in the United States.

Source: Lancet, June 2008

Researchers ID Genetic Variants Linked to Increased Risk of Metabolic Syndrome

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Nutrition researchers have identified five common genetic variations that increase the risk of metabolic syndrome, a group of factors linked to heart disease and diabetes. Another variant they found appeared to protect against the condition.

People with metabolic syndrome have at least three of the following symptoms: abdominal obesity, high blood triglyceride levels, lower good cholesterol (HDL), elevated blood pressure and elevated fasting blood glucose. They are four times as likely to develop heart disease and at least seven times more likely to develop diabetes as individuals without metabolic syndrome.

The investigators at Washington University School of Medicine in St. Louis looked for changes in the CD36 gene, which is located in a region of chromosome 7 that has been linked to metabolic syndrome in several genome-wide studies.

The researchers say linking changes in the CD36 gene to the risk for metabolic syndrome and abnormal levels of good cholesterol is important because as more people in the United States become obese, they also become susceptible to these problems. Better understanding of the relationships between obesity, the gene and disease risk may allow for earlier identification of individuals who are more susceptible to develop metabolic syndrome. Treatments such as medication or lifestyle changes could begin earlier, perhaps preventing or delaying future problems with diabetes or heart disease.

Senior investigator Nada A. Abumrad, Ph.D., the Dr. Robert C. Atkins Professor of Medicine and Obesity Research, first identified the CD36 protein in studies with mice. Her research has demonstrated that the protein facilitates the use of fatty acids for energy. CD36 is located on the surface of cells and distributed throughout many tissues, including fat cells, the digestive tract, heart and skeletal muscle.

The investigators focused on 36 small genetic variations, called single nucleotide polymorphisms (SNPs), in the CD36 gene. A SNP involves a single base-pair change in the DNA.

The team evaluated DNA taken from more than 2,000 African-Americans because variations in the gene are more common in individuals of African and Asian descent than in other racial groups. The researchers expect, however, that these findings also will be applicable in other populations.

“The idea was to look at the different variations in the gene and see whether they were more prevalent in people who also had elevated cholesterol, abnormal blood glucose or the other components of the metabolic syndrome,” says first author Latisha Love-Gregory, Ph.D., research instructor in the Division of Geriatrics and Nutritional Science.

Love-Gregory says the research team demonstrated an association between SNPs in the gene and metabolic syndrome.

“There is additional work to do to determine if the function of these genetic variants actually contributes to the development of type 2 diabetes or heart disease,” she explains. “We do expect that a number of different changes, in both CD36 and other genes, will be related to these diseases. What we’d like to learn, however, is whether the changes identified in the gene alter the CD36 protein in ways that change its function to make a person more vulnerable.”

The team determined that five of the SNPs they examined are more common in people who have symptoms of metabolic syndrome, but a sixth seemed to have a more favorable metabolic effect. The “protective” SNP makes people produce lower amounts of CD36 protein.

Humans have two copies of each chromosome. In this study, people who had the protective variant on only one of their copies of chromosome 7 were less susceptible to metabolic syndrome. But people with two copies of the variant, who were completely deficient in the CD36 protein, did not appear to be protected. They tended to have lower levels of HDL, the so-called good cholesterol.

“A bit less CD36 protein may improve your risk profile, but people need some CD36 function,” Abumrad says. “It’s like requiring a certain level of fat in the diet. Fatty acids are important for optimal function of many tissues — from pancreatic beta cells to skeletal muscle to the heart — but too much fat creates a problem.”

Love-Gregory and Abumrad found that many variants influenced blood levels of HDL cholesterol. Now they are taking a closer look at the relationship between CD36 and HDL cholesterol. Higher levels of HDL normally are considered positive, but because changes in the CD36 gene seem to influence HDL, the researchers want to make sure that the HDL molecule isn’t being altered in composition or function.

“We’re going to follow up on the HDL component of the study,” Love-Gregory says. “We’re also going to look for additional variants in the promoter region of the gene that controls how the gene is regulated. And we’re planning to look for evidence of these gene variants and their associations with HDL and the metabolic syndrome in other populations and ethnic groups.”

Source: Human Molecular Genetics, June, 2008

Differing Brain Connections May Cause Autism’s Social Impairment

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The brains of adults with autism may be "wired" differently from people without the disorder, and this abnormal pattern of connectivity may be responsible for the social impairments that are characteristic of autism.

Using functional magnetic resonance imaging, a team of researchers affiliated with the University of Washington’s Autism Center found that the most severely socially impaired subjects in the study exhibited the most abnormal pattern of connectivity among a network of brain regions involved in face processing.

"This study shows that these brain regions are failing to work together efficiently," said Natalia Kleinhans, a research assistant professor of radiology and lead author of the paper published in the journal Brain. "Our work seems to indicate that the brain pathways of people with autism are not completely disconnected, but they are not as strong as in people without autism."

The study is the first to look at brain connectivity and social impairment, and focused on how the brain processes information about faces. Deficits in face processing are one of the earliest characteristics to emerge in people with autism.

The research team led by Elizabeth Aylward, a UW professor of radiology, examined connectivity in the limbic system, or the network of brain regions that are involved with processing social and emotional information.

Participants in the study included 19 high-functioning adults with autism who had IQs of at least 85. They ranged in age from 18 to 44 and were compared with an age- and intelligence-matched sample of 21 typically developed adults.

The group with autism spectrum disorder included eight individuals diagnosed with autism, nine with Asperger’s syndrome and two diagnosed with pervasive developmental disorder not otherwise specified. The level of social impairment for each autistic participant was drawn from records of clinical observations and diagnoses that confirmed that each had autism.

Each participant had his or her brain scanned while looking at pictures of faces or houses. Participants were shown four series of 12 pictures of faces and a similar number of series showing houses. Each individual picture was seen for three seconds. Occasionally the same face or house picture was repeated, and participants were told to press a button when this occurred.

There was no significant difference on the two groups’ performance, because the task was so basic, said Todd Richards, a professor of radiology and co-author of the paper. "Differences might have shown up if they had been asked to do something more complicated."

However, the two groups exhibited different patterns of brain activity. The researchers focused on the fusiform face area of the brain, a region that is involved in face identification. Compared to the participants with autism, the typically developing adults showed significantly more connectivity between the fusiform face area and two other brain regions, the left amygdala and the posterior cingulate. In addition, autistic participants who had the largest social impairment showed the lowest level of connectivity between the right fusiform face area and the left amygdala and increased connectivity between the right fusiform face area and the right inferior frontal gyrus.

"This study shows that the brains of people with autism are not working as cohesively as those of people without autism when they are looking at faces and processing information about them," said Kleinhans.

Source: University of Washington, June 12, 2008

Study Shows Obesity Is a Major Risk for Heart Failure

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The results of the Multiethnic Study of Atherosclerosis (MESA) identifies "the biological effects of obesity on the heart" as a serious reason for 72 million overweight Americans to worry about their health.

Senior study investigator Joao Lima, M.D., says "Even if obese people feel otherwise healthy, there are measurable and early chemical signs of damage to their heart, beyond the well-known implications for diabetes and high blood pressure. Now there is even more reason for them to lose weight, increase their physical activity and improve their eating habits."

The development of heart failure of some 7,000 mean and women, aged 45 to 84 was followed by researchers conducting the MESA study, which started in 2000. To date, of the 79 participants who developed congestive heart failure 44% were obese with a body mass index (BMI) of 30 or more. They were also found to have higher blood levels of interleukin 6, C-reactive protein and fibrinogen, key immune system proteins involved in inflammation, than non-obese adults. An 84% greater risk of developing heart failure was accounted for by a near doubling of average interleukin 6 levels.

The links between inflammation and the combination of risk factors known as the metabolic syndrome alarmed the researchers from 5 U.S. universities.

The researchers from five universities across the United States also found alarming links between inflammation and the dangerous mix of heart disease risk factors known as the metabolic syndrome. Its combined risk factors for heart disease and diabetes—high blood pressure, elevated blood glucose levels, excess abdominal fat and abnormal cholesterol levels, and particularly obesity—double a person’s chances of developing heart failure.

"More practically, physicians need to monitor their obese patients for early signs of inflammation in the heart and to use this information in determining how aggressively to treat the condition," says Lima, a professor of medicine and radiology at the Johns Hopkins University School of Medicine and its Heart Institute. "Our results showed that when the effects of other known disease risk factors—including race, age, sex, diabetes, high blood pressure, smoking, family history and blood cholesterol levels—were statistically removed from the analysis, inflammatory chemicals in the blood of obese participants stood out as key predictors of who got heart failure," says Lima.

The study found that higher levels of interleukin 6 and a tripling of average levels of C-reactive protein in study subjects increased the possibility of heart failure by 36%.

What this tells us is that both obesity and the inflammatory markers are closely tied to each other and to heart failure," says lead researcher Hossein Bahrami, M.D., M.P.H. Bahrami, a senior cardiology research fellow at Hopkins, says "the basic evidence is building the case that inflammation may be the chemical route by which obesity targets the heart, and that inflammation may play an important role in the increased risk of heart failure in obese people, especially those with the metabolic syndrome."

Each year, nearly 300,000 Americans die from heart failure.

Source: Journal of the American College of Cardiology, May 6, 2008

Children Still At Risk from Lead Poisoning, Despite Programs Promoting Cleaning and Home Repair

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A review of studies shows that children are still at risk of lead poisoning, despite attempts to encourage home cleaning and repairs, and parental awareness.

Lead author Dr. Berlinda Yeoh, a pediatrician at Sydney Childrens’ Hospital in New south Wales, Australia, says of these attempts that "none that have been tried so far have been proven to be effective." The most common cause of lead poisoning in children is ingestion of dust from old lead paint, and Dr. Yeoh cited lead poisoning as an important health issue for children. It can, she said, contribute to behavior and growth problems, anemia, kidney damage, and other physical, cognitive and behavioral impairment.

Although the sale of lead paint in the United States was prohibited as long ago as 1978 children today can still ingest paint from peeling walls, broken plaster or old painted window sills. 12 U.S. studies, encompassing 2239 children, were examined, and analyzed 2 types of parental interventions—educational and environmental. Educational intervention taught awareness of lead poisoning and methods of preventing dust and lead exposure in the home; environmental intervention suggested making repairs, cleaning and painting.

The Cochrane Library carried the review, and the reviewers’ findings that educational programs for parents had no effect on children’s blood lead levels, which was also the case for environmental programs. Soil abatement, or the replacement of lead-contaminated soil around the home, was also analyzed and 2 studies showed that this significantly reduced childrens’ blood lead levels, although insufficient data prevented recommending these practices as effective. Even studies that combined both educational and environmental interventions failed to reduce children’s blood lead levels.

Dr. Yeoh pointed to other sources of lead exposure—at day care or relatives’ home, for example—which might make home dust removal programs ineffective.

A further reason might be lack of time to be cleaning thoroughly, said Dr. Yeoh. Based on these results, "it is difficult to support the use of the interventions examined in this review as a general population health measure, given their cost and the lack of data showing positive reductions in blood lead levels," the authors said.

Susan Buchanan, M.D., a clinical assistant professor at the University of Illinois at Chicago School of Public Health, called the review "a very thorough evaluation of current literature. It takes so little lead dust to poison a child that it doesn’t matter how clean your house is, your child is still going to have exposure to lead dust," she said.

"As adults, our neurological systems are somewhat immune to the dramatic effects of lead," Buchanan said. However, very young children often put objects in their mouths—increasing their ingestion of house dust and dirt—that in turn affects their developing neurological systems, she said.

"We have to use the knowledge we have—there is lead in dust, so as much dust removal as possible should still be recommended," she said. However, to "continue screening is critical because if high blood lead levels are caught, then health department inspectors can be used to point out obvious sources of lead in the home," Buchanan said.

The review noted that a coauthor, Bruce Lanphear, was an investigator in two of the studies included in this review.

Source: Health Behavior News Service