Health Meaning

Strokes inflict 80% less brain damage in mice lacking a DNA repair enzyme, according to a report in the issue of this month Nature Medicine . In normal mice, the enzyme zealous deprives brain cells of energy - trying to repair damaged DNA - for hours after a stroke. The discovery suggests that an enzyme inhibitor may prevent damage in humans after existing drugs have restored blood flow

During a stroke, blood flow to part of the brain is cut off. - So that supply oxygen and nutrients such as sugar. Most stroke research has focused on restoring oxygen to the brain, says Valina Dawson, a neuroscientist at Johns Hopkins University. But research has shown that brain cells continue to die after blood flow is restored, since the renewed metabolism generates free radicals that damage DNA and other cell parts. In response, the cells activate an enzyme called poly (ADP-ribose) polymerase (PARP) to repair DNA damage. Dawson said that to try to repair the DNA of the cell, PARP could seriously deplete energy resources and perhaps even kill the cell.

Dawson and his team first have to mice brain cell cultures that have been bred not to produce PARP. Even when the cells were starved of oxygen and sugar, or exposed to chemicals which release neurotoxins such as nitric oxide, they are not damaged - that up to 65% of the cells from normal mice death when subjected to similar treatment. When the researchers then induced stroke in mice with or without the PARP gene, they found that tissue damage resulting from the mice without the enzyme was 80% less than in normal mice. "The protection was phenomenal and beyond our best expectations," said Dawson. Most tests of drug animal stood between 10% to 30% less damage, and sometimes up to 50%, she added.

The protective effect of PARP inhibition is "striking" and made "a strong case" to examine the role of PARP in the human race, said Thomas Jacobs, a neuroscientist at the National Institute of neurological disorders and Stroke in Bethesda, Maryland.

A new therapy for pancreatic cancer reduced the tumor growth rate in patients in a pilot trial and in a separate study, kept the remote mouse tumors altogether. The treatment, reported in today's edition of Proceedings of the National Academy of Sciences , rallies "killer" immune cells to fight the devastating cancer.

Less than 1% of pancreatic cancer patients live more than 5 years after diagnosis. "There are no successful medical treatment," says Wolff Schmiegel, a gastroenterologist at the Ruhr University Bochum, Germany. In the hope of improving this grim statistic, the group moved to exploit the Schmiegel ability of the immune system to recognize certain cancer cells as enemies by the developer carpet proteins, such as the receptors for epidermal growth factor receptor (EGFR), which stud their surfaces. A cancer cell with a lot of EGFR antibody which attracts many lock onto receptors;. the antibodies, in turn, attract the killer cells that destroy tumor cells increasing the number of receptors on tumor cells, the researchers reasoned, would enhance the effectiveness of what is called the immunotherapy, in which antibodies are administered designed to attract killer cells.

Four years Schmiegel and colleagues found they could increase the levels of EGFR on the cell surface of pancreatic cancer by adding a protein of tumor necrosis Factor- a (TNF- a ) to cells in culture. In their latest work, the researchers injected human pancreatic cancer cells in mice, which quickly developed tumors. Treatment of these mice with TNF a and EGFR antibodies have kept tumors from growing larger, like those of control mice Eightfold inflated.

In a second study, the team Schmiegel treat 26 patients at similar stages of pancreatic cancer with TNF- a and a variable amount of the antibody. The tumors of patients receiving more antibodies increased by less than 10% on average, while those in patients receiving the lowest dose more than doubled in size. Patients receiving the high dose also lived more than twice as long on average as those in the lower dose, but this result was less reliable because of the small number of patients.

The therapy offers hope for pancreatic cancer patients, said immunologist Hilary Koprowski of Thomas Jefferson University in Philadelphia, who says he is "cautiously optimistic" that the treatment will prove a hit long term. "I wish there was no difference in survival rates" between the lower and higher dose groups, he said. Schmiegel now working towards the next stage -. A study with more patients who could provide more reliable information on the survival time

A toxin derived from the skin of a South American frog led to a potential new pain reliever that may lack some of the side effects of morphine. In tests on animals, the drug, which apparently is not opioid receptors but rather by a receptor for the neurotransmitter acetylcholine, has proved effective in blocking the acute and chronic pain. In addition, the researchers saw little evidence that the drug, reported in Science today is addictive or toxic.

The drug's design was based on a compound extracted from the skin of an Ecuadorian frog by chemist John Daly, of the National Institute of Diabetes and Digestive and Kidney Diseases. In 1976, he discovered that the compound, called epibatidine, is 0 times more potent than morphine in blocking pain in mice. Unfortunately, it also caused convulsions and even death. Approximately 10 years later, her lab used nuclear magnetic resonance spectroscopy to determine the structure that resembles epibatidine to that of nicotine. Other experiments have shown that the compound activates the nicotinic acetylcholine receptor.

The research has attracted the attention of a team from Abbott Laboratories Abbott Park, Illinois, who noticed that the epibatidine structure resembles that of the compounds they studied as therapies for Alzheimer ' Alzheimer. Neuropharmacologist Stephen Arneric and colleagues fiddled with their compounds, trying to create a derivative that only kills the pain.

They have now shown that a variant, called ABT-594 is as effective as morphine in acute and chronic pain wetting rats. By placing electrodes in the spinal cord of rats, the researchers also showed that the drug inhibits the ability of nerve cells to fire in response to noxious mechanical and thermal stimuli, but it does not affect the touch response or the gentle heat. The company also found Arneric said that ABT-594 depresses the respiratory system less than morphine does, and it makes the animals more alert instead of the sedative. In addition, in at least one test, ABT-594 appears to be nonaddictive.

Much more work will be needed to determine whether the drug is safe and effective in humans. For example, other researchers point out that ABT-594 mechanism of action raises the possibility that it will lead to other forms of addiction. Abbott has begun safety testing in Europe and hopes to conduct trials in this country as well. "If it works in people, it'll be a whole new kind of pain," said Howard Fields, professor of physiology and neurology at the University of California, San Francisco.

A potential treatment for Parkinson's disease can be in an unusual place: the body of the carotid artery, a small organ in the neck. In February the number of Neuron José López-Barneo and colleagues at the University of Seville in Spain reported that in rats, the carotid body cells-transplanted animals neck in their brains reverse symptoms of an experimental form of dementia.

normal work of the carotid body, nestled in the carotid artery, is to signal your brain to increase your breathing if your oxygen levels in the blood drop too low. The main interest of López-Barneo was in how the carotid body-cells captures the lower oxygen levels in the blood. But, he recalls, colleagues kept stressing that these cells could make excellent candidates for transplantation into the brains of Parkinson's patients to correct their shortcomings. Indeed, movement problems and other symptoms of the disease are caused by the death of neurons, in a part of the brain called the substantia nigra that produce the neurotransmitter dopamine. And because the carotid body-cells are much dopamine, they might be able to compensate for the loss of normal dopamine-producing neurons.

To find out, the Seville team turned to a common animal model for Parkinson screening potential therapies. This involves killing the neurons of the substantia nigra on one side of the rat brain, which then develop an imbalance of movement which causes them to turn around, and exhibiting other symptoms. When the researchers transplanted into the damaged side rats pieces of brain carotid body, they found that the grafts not only survived, but reversed the animals of symptoms, including the imbalance of the movement. There were even indications that the cells could be the production of growth factors that promote the substantia nigra cells remaining to sprout new connections.

These results are "quite fascinating, very promising," said neuroscientist Arnon Rosenthal, who works on Parkinson therapies in the biotechnology company Genentech Inc. in South San Francisco. Carotid-body cells will pass much more testing before researchers can even consider trying them on patients, however, Rosenthal said, they may have an advantage over therapeutic potential competitor. transplantation of fetal neurons Because the cells of the carotid produce so much dopamine. - up to 45 times the fetal neurons - and because they thrive in relatively low concentrations of oxygen in the brain, he says, they can do a better job to correct the symptoms of Parkinson that fetal cells make - and they raise fewer ethical issues

Much new research takes shape held in Kansas City, Missouri, that could one day compete with larger charities biomedical world. With $ 125 million in public funding, the Stowers Institute for Medical Research has begun to renovate a medical center of 55,000 square meters in Kansas City to accommodate an initial staff of 100 people, including 20 Ph.D.s. The institute plans to open five laboratories for basic science in January 00.

According to its co-founder, financier James Stowers Jr., the organization will focus on the genetics of development and growth, with a goal of fighting cancer. For scientific leadership, Stowers has relied heavily on geneticist Leroy Hood of the University of Washington, Seattle, and Eric Davidson of the California Institute of Technology in Pasadena, both members of the National Academy of Sciences.

Stowers, 74, and his wife Virginia, 68, are cancer survivors; according Stowers, "which is what motivated us" to consider funding medical research. "My wife and I wanted to give something more than money for people who have made our success possible." They launched the endowment of the Institute, with 327 million shares $ of the investment company, they founded, American Century funds the couple plans to leave the rest of their assets. - estimated at more than $ 1 billion. - the institute to death If these funds are also developing faster than he managed in Historically, Stowers said, staffing may be worth $ 30 billion in 25 years

Stowers said he has a clear scientific strategy, based partly on the advice of Hood .: "We wanted focus our efforts in one area and not be scatter-gun. " Davidson, who also serves on the advisory board, said, "You can not organize science, but we hope to find and recruit people" interested in "looking at the complex interactions of groups of molecules" using advanced technology. the key to success of the institute recognizes Stowers will be its ability to attract "top scientists" in Kansas City.

An enlarged heart increases the likelihood of death from heart disease in adults. Now it seems that 8% of children and adolescents with high blood pressure - perhaps in 1250 in the United States - also have a disturbing thickening of the heart muscle. The discovery, published in the latest issue of Traffic , suggests that testing for heart enlargement must indicate which children need a more aggressive treatment of risk factors for heart disease.

specifically enlargement-- heart's main pumping chamber of the heart, the left ventricle - was first linked to an increased risk of fatal heart disease in 190, as part of the Framingham study massif of heart disease. Since then, doctors have found that treatment of other risk factors for heart disease such as high blood pressure and obesity, can reduce the relative size of the left ventricle.

Wondering how early in life from this disease develops, cardiologist Stephen Daniels and colleagues from the University Hospital Medical Center of Cincinnati Children interviewed 130 children who had been admitted to the Clinical Hypertension hospital and thus may be more likely to have an enlarged left ventricle. To calculate the relative size of the heart of each child, the researchers scanned every heart with ultrasound. Eight percent of children aged 6 to 23 has reached or exceeded the threshold that defines a high-risk adults. "It is surprising because it suggests that this process is already underway, and these children can be directed to paths for future cardiovascular disease," says Daniels.

Other cardiologists say the test should help guide treatment as well. Samuel Gidding of Northwestern University says children with both high blood pressure and enlargement of the ventricle could be dealt with not only a weight loss program over diet healthy, but also with drugs that reduce blood pressure. "to this very small group of children who clearly detrimental to their heart, we need to be more aggressive in the treatment," he said.

There have been nearly a century since first Alois Alzheimer fibrous plaques found infesting the brains of people with dementia but scientists still do not know with certainty, however-or even if - the plaques cause Alzheimer's disease. Now a trio of studies in the July issue of Nature Medicine opens new avenues for research on the plate with a new animal model for the formation of plaque, a diagnostic tool for identify, and a possible way to break them.

scientists have long suspected that Alzheimer's patients lose their memories and minds when the beta amyloid proteins form aggregates that needle punch holes in the brain cells and kill them. Alzheimer mostly affect the elderly, but scientists have not been able to understand why because they lacked a good animal model of the disease; in previous mouse models, the amyloid plaques formed but brain cells survived. Now neurologists Changiz Geula and Bruce Yankner of Harvard Medical School found such a model: Rhesus monkeys. They injected tiny amounts of amyloid protein in the brains of monkeys and found that the old rhesus monkeys developed symptoms, but young Alzheimer's monkeys remained healthy.

Research on plates was also hampered by the lack of a good method for diagnosing Alzheimer's disease in living patients. A new diagnostic test, created by Detlev Riesner and colleagues at Heinrich-Heine-Universitat in Dusseldorf, Germany, can help identify the plates long before brain cells die. The test, which measures levels of beta-amyloid plaque in the spinal fluid, successfully diagnosed 15 Alzheimer's patients and was not triggered by 19 people with other neurological diseases.

If the plates show a crucial link in Alzheimer's disease, a treatment that breaks down can repair the damage. Claudio Soto and colleagues at New York University Medical Center may have found a protein fragment that does exactly that. In rats and human nerve cells in tissue cultures, these "beta sheet breakers" not only prevent amyloid plaques from forming, but also dissolve existing plaques.

Taken together, the new studies create interesting new tools in the fight against Alzheimer's disease, says Robert Szarek, a pathologist at Queens University in Kingston, Ontario. early diagnosis could help doctors intervene and using a new therapy to preserve brain cells, he said. and if the beta sheet breakers are effective in monkeys and rats, they could also help treat Alzheimer's patients. But this should not be simple. for treating humans, the researchers must still find a way to deliver fragments of proteins past the blood-brain barrier, which prevents movement of proteins into the brain, and the site of the plates. Kisilevsky adds, "These are formidable problems."

A new drug can block the symptoms of schizophrenia as in rats without apparent side effects. The work, described in Science tomorrow , suggests a new approach to drugs for schizophrenia that may one day lead to better therapies for the disease, which affects 1% of the population of the United States only.

These drugs are sorely lacking. Current drugs against schizophrenia, known as neuroleptics, are designed to relieve the symptoms of the disease by blocking the action of a brain chemical signal, dopamine. But as patients who take the often see reductions of paranoia and hallucinations, medications provide little relief of other symptoms, such as poor attention spans, confused thoughts, and difficulty interacting with other people. In addition, neuroleptics often cause disturbing side effects, including uncontrollable tremors similar to Parkinson's patients

Phencyclidine of psychoactive substances, or PCP, offered tempting tips that a different approach could to work:. Blocking the activity of another neurotransmitter called glutamate. PCP induces symptoms of schizophrenia as in healthy people. Following these observations, neuroscientists Bita Moghaddam and Barbara Adams of Yale University School of Medicine and the Veterans Administration Medical Center in West Haven, Connecticut, PCP administered to rats who develop symptoms such as the frenzied race and turn his head thought parallel psychotic symptoms in humans, and examined what happens to the brain glutamate levels in animals. Although previous work has suggested that they should go down in response to the CFP, Yale workers found instead they jumped. Moghaddam then speculated, she recalls, that "if we block the activation of glutamate, maybe we can block these behavioral effects."

To avoid side effects, Moghaddam and Adams wanted to block the glutamate activity in the parts of the brain where it can be high. So, they turned to a drug called LY354740, which is under development at Eli Lilly & Co. in Indianapolis for other psychiatric disorders such as anxiety. By binding to metabotropic receptor called glutamate on nerve endings glutamatergic releasing LY354740 dampens the output of the transmitter, but only when the too high. when Moghaddam and Adams rats given the drug before Lilly administer the CFP, they found that glutamate levels went up in the prefrontal cortex, one of the regions of the brain that breaks down in schizophrenia. the six LY354740-treated rats also remained calm and showed little behavior nods, compared with controls who received only CFP.

Encouraging results in rats do not guarantee that the approach will work in humans. Yet, says Horvitz Jon schizophrenia researcher at Columbia University in New York, "it's an awesome job. This is a promising way to a drug that alleviates the symptoms of schizophrenia."

Association today presented Alzheimer's largest single research grant, he has never given to a husband and wife team at the University of Pennsylvania School of Medicine in Philadelphia. Neuropathologist John Trojanowski and Virginia Lee neurobiologist use the grant of $ 1 million over the next five years to develop new tests for the diagnosis of Alzheimer's disease in its early stages.

Since some cases of Alzheimer's disease resemble other neurodegenerative diseases such as Parkinson's disease, Trojanowski and Lee intends to look for ways to identify Alzheimer's disease true. "To get good treatment in drug trials you need to know what you are dealing with," says Trojanowski. He and Lee are the players in the field of Alzheimer's disease well known, having collectively published over 100 Articles on neurodegenerative diseases.

Association of Alzheimer's disease has designed the Pioneer award with the needs of innovative scientists in mind. Unlike many other subsidies, the price enables researchers to save unspent funds for unexpected opportunities that may arise. other scientists say the price is generous enough for academic researchers to pursue drug development projects that otherwise would not be possible without corporate financing. "Therapeutics was the field of biotechnology and pharmaceutical industry, and this could change that, "says Sam Sisodia, a molecular biologist at the University of Chicago. The Alzheimer's Association will award three more $ 1 million grant to Pioneer in June 1999.

W ASHINGTON , DC - Worried about an imminent new era of terrorism, a scientific committee urged the government today to redouble their efforts to protect civilians against emerging biological and chemical threats.

The report, published by the Institute of Medicine (IOM), asks the public health service to build local health surveillance systems and emergency services. It also aims to create a national stockpile of antidotes and vaccines that could be transported to the site of an attack across the United States. The panel, chaired by the specialist in Emergency Medicine Peter Rosen of the University of California, San Diego, also has a long list of research needs. Among other things, the report recommends studies on how to conduct medical triage large-scale, the development of new biohazard detection equipment, better vaccines against anthrax and smallpox, and more effective protective equipment.

While the Pentagon has invested billions of dollars to protect troops against biological and chemical attacks, the report notes, these "military traditional approaches" are not suitable to treat civilian settings, where attacks future may occur. Despite the "very low probability" of a terrorist attack on a particular site, IOM offers a 220 page program to remedy the absence of civil preparedness. Many of the proposals, according to the report, are intended to strengthen local networks of public health, which makes the "valid even if no attack never happens."

The IOM report was warmly welcomed at the Department of Health and Human Services (HHS), the home of the public health service. Margaret Hamburg, the assistant HHS secretary for planning, acknowledges that "we are very badly prepared" for the kind of panic that would result from a bioterrorist attack and HHS spokesman Campbell Gardett said. "We welcome the report" adding that "we are currently developing a plan that will detail how we will use" approximately $ 150 million Congress gave HHS for bioterrorism defense in a special 1999. appropriation

- E LIOT M ARSHALL