Health Meaning

The rapid paralysis that killed baseball legend Lou Gehrig begins when neurons in the brain and spinal cord die mysteriously. Now, experiments with mice suggest a possible new treatment :. Drugs that push cell suicide

Amyotrophic lateral sclerosis (ALS), as Lou Gehrig's disease is formally known, crippled adults in their 40s and 50s and brings death within 1-5 years. The only treatment available just slightly increases the chances of survival, but it only works in the early phase of the disease. No other drugs were developed, because researchers were simply some clues about what went wrong. A breakthrough came in 1993, when they discovered that a gene called SOD1 was mutated in many ALS patients. Just how the mutation leads to disease is still unclear, but studies of human patients and transgenic mice with the defective gene have suggested that the mutation activates two enzymes called caspase-1 and -3. Caspases are beginning a process called programmed cell death, or apoptosis, which normally allows the orderly removal of aging, inefficient, or cancer cells. increased caspase activity in ALS has been suggested that apoptosis is unleashed, killing healthy and vital neurons.

To find out, use neurosurgeon Robert Friedlander and colleagues from Brigham and Women's Hospital in Boston, Columbia University, and the University of Chicago first several staining techniques to confirm that caspase was actually activated in mice with SOD1 mutation. Then, they used small pumps to inject a thread of a caspase inhibitor called zVAD-fmk directly into the brains of the mutated mice, while another group received infusion of a solution without the inhibitor.

The experiment was started when the mice were 60 days; from there, the animals receiving the caspase inhibitor took about 63 days to develop symptoms of ALS 20 days longer than the control group. They also lived 27 days more, reports the team in April 14 Science . Microscopic examination of their spinal cords showed the treated mice had more motor neurons left than controls. "We have not found a cure," warns Friedlander, but he is optimistic that the caspases can be a good lead for new drugs.

"The study offers an interesting new approach to treatment," agrees pharmacologist Mark Gurney Pharmacia Corp. in Kalamazoo, Mich. "It's an important step," adds -. ". But not a home run "

A Chinese herb that has damaged the kidneys dozens of people to the Belgian diet in the 190s was found to pack a second shot vicious fist - cancer or precancerous lesions, according to a report in the June 8 issue of on New England Journal of Medicine . These findings support one of the strongest links yet between the use of a product herbal and cancer, and critics argue, should serve as a dire warning that dietary supplements need more regulation.

In 1992, the symptoms of kidney failure started showing up among the Belgians who had taken a mixture of Chinese herbs and Western medicine prescribed for weight loss. A closer examination, the researchers found a mix-up Herbal: Instead of containing the plant Stephania tetrandra as labeled, the herbal pills contain derivatives of Aristolochia fangchi , a plant known to be loaded with toxins and kidney powerful carcinogens. Of the approximately 10,000 people who took the pills, at least 70 had complete renal failure, and 50 others have sustained damage to kidneys serious enough to require treatment.

The first kidney cancers were found in these patients in 1994. To discourage the appearance of the disease in more patients, doctors of the Erasmus Hospital in Brussels advised those whose kidneys and ureters had ceased to function to consider surgical removal of organs. Thirty-nine people have opted for the operation in recent years. When a team of researchers coordinated by a kidney specialist Joélle Nortier inspected the excised tissues, they were surprised to discover that the cancer had already developed in 18 patients, and precancerous lesions (dysplasia) were present in 19 others. prescription records confirmed that patients who had taken over diet pills were more likely to have cancer. As further evidence that Aristolochia was to blame, the team found that the DNA in the kidneys of these patients performed typical defects of damage caused by toxins from the plant.

Belgium stopped importing Aristolochia and mixtures of plants that may contain in 1992. But there is little to prevent a similar disaster in the United States and other countries, said David Kessler, dean of the Faculty of medicine at Yale University and former commissioner of the Food and Drug administration (FDA). Under the Dietary Supplement Act 1994, manufacturers must not show the safety or efficacy of a herbal remedy prior to marketing, and the hands of the FDA linked "until the horse is out of the barn, "he said.

Even so, counters Varro Tyler, Dean retired from Purdue University pharmacy school in Indiana, the FDA could be even more vigilant, specifically testing the products are on the market and prohibit them if they are harmful. "They must take the initiative, they have not done," said Tyler. But he agrees that until the laws are expanded, consumers can not be sure that they get the health store is safe.

alcoholism is difficult for anyone to hit, but people who develop early in life are less likely to sober up. Now a study shows that a new drug to help the alcoholic drink less. The drug does not work for alcohol late onset, adding the evidence for different types of alcohol.

The drug called ondansetron, blocking a receptor that responds to the neurotransmitter serotonin, which appears to play a role alcoholism. Ondansetron looked promising in a preliminary study soft volunteers. The 16 men who participated indicated that the drug has stifled the pleasure of drinking and curbed their desire for alcohol. "Conducting a clinical trial was the next logical step," said Bankole Johnson psychiatrist at the University of Texas Health Science Center at San Antonio.

The team of Johnson tested ondansetron in the early and late onset alcoholics, defined as those who developed their drinking problems before or after age 25 among 271 alcoholics, some received ondansetron and others received placebo for 11 weeks. early onset alcoholics who got the drug were 20 more days without alcohol than the placebo. When they did consume alcohol, they drank about 40% less, the team reports in the August 23 issue of Journal of the American Medical Association. The drug has not changed late alcohol consumption habits.

This difference in efficiency is important, said Henry Kranzler psychiatrist from the University of Connecticut School of Medicine in Farmington, because it suggests that early alcohol and late-onset are distinct subtypes. Indeed, other drugs that affect serotonin such as Zoloft and Prozac, appear to have varying effects on the disease. "This is an area that seems to come of age," said Kranzler efforts to find drugs to treat different types of alcoholism.

Related Sites
National Institute on alcohol abuse and alcoholism Addiction Division
alcohol and drugs, University of Texas Health science Center

Philadelphia - Deafness may be more common, according to a study presented here on October 6 at a meeting of the American society of Human Genetics. Researchers believe that increased opportunities for deaf people to meet and marry each other can lead to an increased frequency of an important class of deafness-causing mutations.

Gene mutations in over 0 locations on the genome because of inherited deafness, which represents about half of deafness in general. Recently, clinical geneticists reported that defective copies of a gene called Cx 26 cause about 35% of all cases of deafness.

This number seemed remarkably high at Walter Nance, a geneticist at Virginia Commonwealth University in Richmond. From a statistical analysis of data on American families of the 19th century with deaf children, it considered that, in those days, Cx 26 mutations accounted for only 17% of hereditary deafness. Nance said that intermarriage could explain the increase of 26 Cx deafness, because both parents with this mutation will always have deaf children. Marriages between deaf have been on the rise since the development of sign language and the establishment of schools for the deaf in the last 2 centuries.

To test this theory, Nance traveled to Mongolia, where marriage between deaf is still relatively rare. There he collected the DNA of about 100 deaf and hearing 150 people. As he suspected, very few deaf Mongolians had mutations in Cx 26.

Not everyone is convinced. "It is a reasonable assumption, because deaf people tend to marry Deaf" said David Kelsell, a geneticist at Queen Mary and Westfield College in London, UK. But he says Nance needs to repeat the study in other ethnic populations, because the frequency of mutations Cx 26 may have been different in Mongolian to start. Nance accepts; his lab has already started to examine the frequency of Cx 26 mutations in Turkey.

If his theory is correct, Nance said, it would mean that mixed marriages are not only to increase the percentage of deafness due to Cx 26, but also the prevalence of deafness. So far, it has been difficult to measure because there are no good data on the occurrence of deafness in the past.

Related Sites

summary of Nance in the meeting of the American Society of Human Genetics

homepage Connexin deafness

hereditary hearing loss homepage

National Institute on deafness and other communication disorders

By following clues left by thalidomide - the drug that caused birth defects infamous - researchers have identified a gene on chromosome 7 which can be responsible for some cases of autism. Meanwhile, another study showed that long stretch of chromosome 15 can hold even more genes that predispose children to the disease.

Autism affects about 1 in 500 children, preventing them to connect with others or communicate and causing repetitive and stereotyped behavior and often mental retardation. Researchers have implicated at least three and possibly up to 15 genes in disorder, and they suspect that toxic chemicals may also play a role.

high levels of studies thalidomide revealed autism and facial deformities and ears among those exposed to the drug in the fourth week of gestation. Similar brain and facial defects occur in mice engineered to lack HOXA1 , a gene known to be involved in early development. That's why a team led by Patricia Rodier at the University of Rochester in New York decided to look for a mutation in HOXA1 in humans.

57 autistic patients tested by the team, nearly 40% had a mutation in one copy of the gene (one of them had mutations in both). Of 166 family members who were also tested, more than a third had the mutation and those who are more likely to have mild versions of autistic traits. Among 225 unrelated controls, only 25% had the altered gene, the team reports in the December issue of Teratology .

The study is "a very important scientific achievement," says Marie Bristol -Power, who chairs the Autism Coordinating Committee at the National Institutes of Health (NIH) in Bethesda, Maryland. neuropathological data showed that everything that happens in autism occurs in the first 7 months of gestation. This research contributes to narrow the window of time for the first 3 to 4 weeks, she said.

Another discovery appears in the December issue of American Journal of Medical Genetics. Researchers led by Anne Spence and Moyra Smith at the University of California, Irvine, say an autistic 7 year old girl missing a stretch of about 1 million base pairs on one copy of chromosome 15 . previous linkage studies also pointed out that the area of ​​the chromosome, so the genes that are normally found in the missing area are obvious candidates that may play a role in autism, the team concludes.

network autism NIH consists of 10 research programs at different institutions can now detect more people to HOXA1 and refine the search section on chromosome 15, said Bristol -Power. Finally, the work may lead to new tests that could predict whether a fetus is at risk for autism, or even drugs to treat the disease, she added.

Autism Research at the University of Rochester

NIH information on autism page

website of autism at the National Institute of child health and human development

homepage Moyra Smith

Better known as a virtual institute, the Howard Hughes Medical Institute (HHMI) will soon be a vast expansion in bricks and mortar. The biomedical charity heavyweight announced last week it will spend $ 500 million over 10 years on a research center that will develop advanced bioinformatics, imaging, and other tools. It will also serve as an incubator for visiting scientists -. Even those who are not HHMI investigators

Intramural Research campus will have a major departure for the $ 12 billion HHMI. Since 1953, he has focused on the financing of an elite corps of scholars on college campuses across the country and nurture a stable of educational and training programs.

The Institute will break ground in 03 on a 112 hectare site in Virginia, about 45 minutes drive from the current HHMI headquarters in Chevy Chase, Maryland. Plans call for a complex of buildings with 46,000 square meters of space on the site. The campus, which will eventually accommodate up to 300 scientists and has room to double in size, is expected to open in 05 with an annual operating budget of about $ 50 million.

The interdisciplinary center is intended to feed the insatiable appetite of the investigators for the high-tech tools such as bioinformatics software and electron microscopy at low temperatures. HHMI officials wanted to ensure that all HHMI investigators - not just those on the rich campus -. could have access to these tools and expertise needed to operate them

The few researchers who have heard about the closely guarded plans HHMI are enthusiastic: "It looks like they will create a large playground "that will encourage the kind of mixture between disciplines needed to develop these technologies, says neuroscientist Carla Shatz Harvard medical School, a former HHMI investigator who now serves on its advisory board doctor.

Related site

Howard Hughes Medical Institute

When a protein is unable to do its work, another can step in to take his place. That is the encouraging conclusion of researchers who discovered that overexpression of a protein called integrin reduces muscle degeneration in mice with symptoms of muscular dystrophy. The discovery, published in March 19 issue of Cell Biology Journal , using a day could identify drugs that slow the deadly disease.

Duchenne muscular dystrophy (DMD) hits a 3,500 boys worldwide. No other hereditary disease kills more children. Patients experience progressive muscle weakness and usually die before age 20. They lack a protein called dystrophin, which attaches muscle cells to external scaffolding between cells. Without this link, the muscle tissue disintegrates. Dystrophin but is not the only protein that anchor the cells to the extracellular matrix is ​​known; and made a related protein, a 7 b 1 integrin. A team led by Stephen Kaufman at the University of Illinois at Urbana-Champaign wondered whether it could replace dystrophin.

The team began with mice that do not make dystrophin or a similar protein utrophin. These mice already produce about twice the normal levels of integrin in muscle tissue - probably to partially offset the loss of other proteins. Outfitting in mouse embryos with rat integrin gene, Kaufman doubled again their levels of integrin. The engineered mice lived an average of 38 weeks against 12 weeks for the dystrophic mice. They also showed less severely curved spines, greater mobility, and less weight loss.

parallel work of Kaufman findings at the University of Oxford that overexpression of utrophin also relieves muscle degeneration. The Oxford group is now testing drugs that could increase the levels of utrophin in the cells, and Kaufman hopes to follow the same route with integrin.

If these compounds are found, and patients receiving treatment at the first sign of weakness --generally 2 or 3 years - the strategy could work in theory explains cell biologist James Tidball University California, Los Angeles. But the disease is not progressing quite the same way in mice and people, Tidball warns. "It is difficult to say when or if [this research] would actually lead to a clinical application."

Related Sites

paper Summary in Journal cell biology
laboratory Stephen Kaufman
utrophin work at Oxford, described by the financing of the agency
UCLA Duchenne muscular dystrophy Research Center

The anti-leukemia drug known as Gleevec or STI-571 was announced as the vanguard of a new generation of drugs against cancer of the designer. Unfortunately, some advanced leukemias become resistant to treatment. Now, a new study shows that this resistance can be caused by either mutation or gene amplification makes the target of the drug.

Most drugs against cancer were discovered by screening thousands of random chemicals to see if cancer cells kill. But STI-571 was designed specifically to inhibit certain kinases enzymes, including those produced by the Bcr-Abl oncogene that fuels the growth of cancer cells in chronic myeloid leukemia (CML). Almost all patients treated in the early stages of CML respond to the drug, and some have been in remission for over 2 years. However, the drug was less effective in patients with advanced disease. These people sometimes go into remission on medication - which almost never happens with older treatments -. But 80% relapse within one year

To understand the mechanism of this resistance, Charles Sawyers of the University of California, Los Angeles, and colleagues first analyzed the activity level Bcr-Abl kinase in tumor cells of 11 patients who had relapsed. They detected high levels in all cells - an unexpected finding, because these cells are genetically unstable and could have thwarted the drug by another change. In six patients, the reason turned out to be a point mutation that alters the Bcr-Abl enzyme, allowing him to avoid drugs, while maintaining the kinase activity which stimulates the growth of tumor cells. In three others, additional copies of the gene overwhelmed the drug by producing more enzyme he could handle.

The fact that changes in the target enzyme responsible for drug resistance is encouraging, said Brian Druker of Oregon Health Sciences University in Portland, because it means targeting the kinase Bcr Abl or protein interacts with another promising strategy for the fight against cancer. Future treatment options include the design of additional kinase inhibitors that are given with STI-571, because the enzyme should be less able to become resistant to all drugs at once.

The AIDS virus can cause a release of amyotrophic lateral sclerosis (ALS), also known as the disease of Lou Gehrig, who can be effectively treated with antiretroviral drugs, according to two studies published in the September 25 issue of Neurology . The results strengthen the case for a viral cause of ALS and show that at least a few cases of motor neuron disease can be reversed.

As ALS patients become sicker, their motor neurons degenerate, causing muscles to atrophy throughout the body. Despite decades of research, it is still unclear what kills neurons. Researchers have long suspected a virus, possibly related to HIV or polio, but the evidence was circumstantial. To see if HIV has been associated with motor neuron disease, neurologist Antoine Moulignier the Rothschild Hospital in Paris, France, and colleagues examined the records of 1,700 patients with HIV or neurological symptoms that were treated the hospital between 1987 and 00.

researchers identified six patients infected with HIV who have developed symptoms of ALS, affecting 27 times higher than the general population. The syndrome developed much faster than ordinary ALS, a few weeks or months, instead of 2 to 5 years; it also struck at a younger age. The researchers tested tissue samples to rule out other causes of neurodegeneration, such as herpes, cytomegalovirus and syphilis. Although ordinary SLA is irreversible, two patients with the syndrome recovered after new antiretroviral drugs have beaten the virus into submission.

In a separate document, neurologist Daniel MacGowan's Beth Israel Medical Center in New York and colleagues report a similar case: a 32 year old woman who quickly developed symptoms of ALS and was quickly found HIV positive . At first, the woman was bedridden, eat through a tube and unable to speak. She recovered completely after treatment for one year with three antiretroviral drugs that made undetectable levels of the virus.

The New York case was "a kind of revolutionary because most ALS syndromes are not getting better," says neurologist Rowland Lewis of Columbia University in New York City. Reports indicate that researchers should test patients to see if HIV infection increases the risk of symptoms of ALS-like, and "he again raises the question of whether the SLA is itself caused by another persistent viral infection, "he concludes.

Related Sites

Background on ALS, the National Institute of neurological disorders and Stroke
General Information HIV / AIDS Centers for Disease Control and Prevention

Once leptin seemed to be the ultimate fat-loss drug :. A hormone suppressing appetite which lack natural causes obesity. Boost blood levels of some of leptin, the researchers suspected of obesity, and they had to eat less. A clinical trial has vetoed the idea when obese people do not respond to treatment with leptin. But a new study shows that this can lead to low leptin chubbiness, suggesting that the hormone might help some people shed pounds.

In 1994, scientists discovered that mice missing both copies of the gene for leptin develop excessive body fat, extreme hunger, and infertility. Shortly thereafter, endocrinologist Stephen O'Rahilly of Addenbrooke's Hospital, Cambridge, U.K., identified two cousins ​​with defects in both copies of their leptin genes. They produce virtually no leptin and show the characteristics of a mouse leptin deficiency. Parents of children are severely obese, even though each carried a defective and one normal copy of the leptin gene.

Now O'Rahilly and colleagues report that having a defective copy of the leptin gene does not affect the weight of a person, even if the effect is more subtle than people with two bad copies of the gene. The team found that people with one good copy of the gene have about half the normal hormone levels. Apparently, following the 13 people they studied end up heavier and packed with a significantly higher percentage of body fat than the family with two normal copies of the gene for leptin, the team reports in the November 1st issue of Nature . O'Rahilly said that in a separate unpublished study people with both leptin gene knockout match "extremely well" to the leptin therapy, although they have not tested people with just a bad copy of the gene.

"We now know that to have a little less than the normal amount of leptin is enough to cause a problem with body fat and weight," says obesity researcher Jeffrey Flier of Beth Israel Deaconess Medical Center in Boston. And with low leptin levels is a treatable disease. As O'Rahilly said, "There could be an obese subgroup with low levels of leptin equivalent, of which at least could be worthy of a clinical trial. "

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Facing a barrage of criticism on studies in which dosent business people with pesticides to determine chemical toxicity, the Environmental Protection Agency ( EPA) is looking for outside advice. On 14 December, the agency asked the National Academy of Sciences (NAS) to help decide whether to accept these controversial data.

A law adopted in 1996 has set new safety limits for pesticide product. Therefore, industry researchers have increasingly paid volunteers exposed to pesticides in order to determine the minimum level of a toxic substance that causes effects such as headaches, nausea, and changes in the activity of enzymes in the blood. Although companies say human experiences are preferable to animal studies in establishing realistic standards, these types of tests remain controversial. Clinton era EPA chief Carol Browner prohibits the agency from the use of human data after activists argued that the tests - unlike drug trials - show no benefit to the health of participants. And an EPA advisory group that has struggled with the issue for more than 2 years ( Science January 1, 1999, p. 18) allowed some human pesticide studies but recommended minimum response tests.

EPA revived controversy last month when he announced that the agency had resumed consideration of human Pesticides data and develop a policy for these tests. On December 14, in an about-face, the EPA announced that it suspend these studies until weighs NAS. The agency wants to know, for example, if a toxicity study on humans should be regarded as "unacceptable" and how it should evaluate studies that have been done according to the ethical guidelines that govern research funded by the federal government .

Outsiders say that the agency should develop formal guidelines for human studies if it will encourage them. Bioethicist Arthur Caplan of the University of Pennsylvania in Philadelphia, a member of the advisory committee, said EPA is "desperately needs a policy."

report on human pesticide tests the EPA advisory board
environmental information on the working group on human testing

a rare experience with a man of brain death has added weight to the idea that the blood vessels in different parts of the body are separate. A team of biologists infused 1 billion different peptides in humans to determine which blood vessels, they went to. Their findings suggest the possibility of designing cancer drugs that target specific tissues.

whereas cancers are often localized in specific tissues, drugs to treat the disease are rarely selective. One solution might be to exploit differences in the molecular signatures of blood vessels that feed tumors in various body parts. For example, a drug designed to target peptides - small chains of amino acids - in the walls of tumor feeding vessels in the liver could stifle tumor blood supply without affecting the healthy tissues in the body. But scientists are only beginning to identify home peptides on which the blood vessels in mice, and some fear the results may not translate into humans.

Wadih Arap and Renata Pasqualini, a husband and wife team of biologists cancer MD Anderson Cancer Center in Houston, Texas, learned about a 48-year-old brain-dead man in the unity of ICU of the hospital. The family of the man wanted to donate his organs, but his advanced cancer made it impossible. Instead, the family agreed to let Arap and Pasqualini infuse their entire library of peptides in human body. The study underwent ethical review by several groups before being approved.

Before the man was kidnapped on life support, the researchers took samples of his muscle, skin, bone marrow, prostate, and fat. They then sequenced hundreds of peptides of each tissue type. To double-check that the peptides were injected demanding tissues, they related - key if they are to be useful therapeutically - the team focused on a peptide that has turned into the blood vessels of the prostate. This peptide thus bound to the tissue of the prostate, but not in skin samples. The reverse is true for a peptide found on blood vessels in the skin, they report in the February issue of Nature Medicine .

By setting a specific peptide known to migrate to certain blood vessels in a cancer-killing drugs, you can "get your smart drug to a particular site," said Bruce Zetter, a cancer biologist at the children's hospital Boston. the work is very promising, he says, but it can move slowly until experiments with brain-dead patients gain greater acceptance among clinicians.

Related Sites

house Renata Pasqualini page
home page of Wadih Arap
Background of angiogenesis

SALT LAKE CITY -. A ten-year study in 10 hospitals provided new evidence that one of the major classes of antibiotics is losing its effectiveness. The study, presented here on May 20 at the General Meeting of the American Society for Microbiology, shows that hospital use so-called fluoroquinolones has increased significantly, so has bacterial resistance to these drugs.

fluoroquinolones are a broad class of antibiotics widely used. His most popular member is ciprofloxacin, or Cipro - antibiotic coal-slaying fame - that doctors prescribe to treat more than 15 types of bacterial infections. Experts have warned for some time that the overuse of fluoroquinolones lead to increased resistance, but cutting their use has been difficult. This is particularly worrying because a bug that is resistant to fluoroquinolone usually survives the others.

Marcus Zervos and Ellie Hershberger William Beaumont Hospital in Royal Oak, Michigan, and colleagues at nine other hospitals followed the use of all fluoroquinolones during the last decade, while frequently testing the sensitivity of the four microbes that cause infection - Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Proteus mirabilis - to ciprofloxacin. They found that in all but one hospital, the use of fluoroquinolones, expressed as the number of doses administered to the patient daily on average, had increased - in one case by 264%. At the same time, the four bacteria became less sensitive, and more in hospitals where the use climbed.

In one hospital where antibiotic use declined, however, Cipro had lost some of its punch, and he had even become more effective in killing Pseudomonas . The decrease in Pseudomonas susceptibility to Cipro in nine hospitals - which ranged from 4% to 45% - is particularly disturbing, the researchers say, since some other drugs can fight against this microbe

colleagues say the study - one of several on the increasing resistance presented at the meeting - is another warning sign that doctors might soon be left without their most powerful weapons. And the liberal prescribing practices is only one of the causes of the problem, says Stuart Levy, a microbiologist at Tufts University in Boston and president of the Alliance for the Prudent Use of Antibiotics (APUA). Another major cause is the use of antibiotics as growth promoters in livestock ( Science , 5 May 00, p 792.) - a practice that APUA hope soon be banned

Related Sites
learn more about fluoroquinolones
Alliance for the prudent use of antibiotics
Program of the American Society for Microbiology general meeting, with finder abstract

fighters malaria have bad news this week. A new analysis reveals that the microorganisms responsible for the disease have much greater genetic variability than previously realized, which means they might have more laps than researchers thought to escape to drugs and vaccines.

Plasmodium falciparum , the single-celled parasite that most deadly cause of four different types of malaria, gave researchers struggling since the 1970s, when it developed chloroquine resistance "wonder drug." There are ten years, scientists have found that large populations of the parasite died off between 3000 and 5000 in the last few years, creating a "bottleneck" that reduces the genetic variability of the species This led to the hope that new effective drugs could be easily developed -.. and the objections of some malaria researchers thought that the pathogen was more complex to cut through the controversy, parasitologist Xin-zhuan Su of the National Institute of allergy and infectious diseases in Bethesda, Maryland, took another look at the bug genes.

Su and his colleagues sequenced 204 genes in each of the five Plasmodium isolates from around the world - the largest survey yet. In the July 18 issue of Nature , they report that 118 genes showed at least a difference when the isolates were compared. Using these genetic differences to rebuild the Plasmodium family tree, the team believes that isolates branched off from the other there are between 100,000 and 180,000 years. Su stressed that this more accurate value for Plasmodium "age corresponds to the first explosion of the human population, where the increasing number of armed dramatically helped the parasite to diversify its genome.

In another study in the same issue, Su and his team hotspots of genetic variation on chromosome 14 of Plasmodium in 87 different isolates compared, some of them sensitive to chloroquine and other resistant to chloroquine. They found that mutations occurred most often in the gene that allows Plasmodium to pump chloroquine on itself. The remaining mutations can be grouped into four related items, suggesting that Plasmodium won the chloroquine resistance four times, once in each set genetically distinct.

The results are "bad news," says geneticist Andrew Clark populations of Cornell University in Ithaca, New York. The extent of genetic variability and Plasmodium "The history" makes you think, 'Whoa - these guys will be able to adapt quickly enough to new drugs, "Clark said these results. confirm that vaccines should target multiple aspects of parasite infection at the same time, parasitologist adds Thomas Richie of the Naval medical research Center in Silver Spring, Maryland.

Related Sites
malaria Xin-zhuan Su Genetics Section
NIAID malaria information from the World health Organization

A new skeletal control mode is out of the closet. A study concluded that the hormone leptin, long known to be involved in obesity, is by the sympathetic - "fight or flight" or - branch of the nervous system to suppress bone formation. The results provide the first evidence that the nervous system regulates bone cells and suggest that beta blockers, high blood pressure medications commonly prescribed to suppress the sympathetic nervous system, could also fight against osteoporosis.

The first indication of a link between leptin and bone came from the observation that obese people, who tend to be less sensitive to leptin, have strong bones. Studies conducted by geneticist Gerard Karsenty at Baylor College of Medicine in Houston confirmed the connection in mice, showing that mice deficient in leptin accumulate their bones and their body weight ( Science NOW, 18 January, 00). But how the hormone delivered his message remained mysterious.

The reports now Karsenty team in the November 1st issue of cell that the nervous system plays a key role. Researchers have joined the systemic circulation of two mouse leptin less and perfused leptin in the brain of a. Bone cells responded that in the mice that received leptin, a result involving the nervous system rather than a message carrying blood. Leptin appears to act through sympathetic nervous system: The mouse bone devoid of norepinephrine - the neurotransmitter of the signing of the sympathetic system - didnt respond to leptin treatment, the team found. Finally, mice treated with beta-blockers maintained normal bone mass, even with their ovaries removed. This condition normally stimulates bone loss, thus increasing the possibility that drugs could fight against osteoporosis.

"It is the elegant science," says immunologist Steven Teitelbaum of Washington University in St. Louis. The work creates a "whole new vision of how bone cells are regulated." However, Teitelbaum warns if the results in mice will apply to humans is still open to question. If the results generalize adds Gideon Rodan, a biologist bone cells in the Merck research laboratories in West Point, Pennsylvania, it might be possible to develop beta blockers that increase bone strength without adverse effects on blood pressure.

Related Sites
bone formation and bone
bases sympathetic nervous system
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To prolong the lives of AIDS patients, doctors rely on a battery of antiviral drugs with side effects that are often as damaging as those of chemotherapy. An alternative long sought to antiviral medication is immunotherapy, in which immune cells specific to a patient are removed, trained to fight against the virus, and are returned to the bloodstream to mount an attack. Reporting in the January issue of Nature Medicine , Wei Lu and colleagues from the University of Paris described the first use of immunotherapy to successfully treat AIDS in monkeys.

HIV virus evades the immune system by hiding inside the same cells that normally fight infection - T cells - and causes AIDS by killing them slowly, opening the door for opportunistic infections and cancers. Lu's team has tried to counter this Trojan attack in 14 macaque monkeys infected with SIV - a relative of HIV that causes AIDS in nonhuman primates - by growing dendritic cells monkeys, cell Scouts seize foreign agents from the bloodstream and present them to T cells to trigger immune responses. The researchers incubated dendritic cells with SIV treated with AT-2, a chemical that makes the virus harmless by permanently blocking viral replication, and then they returned these cells formed SIV monkey's bloodstreams.

Lu said 'd just hoped to find a measurable effect of this immunotherapy on SIV infection, but he was surprised by how effective it was. Within 10 days, SIV viral load in infected monkeys was 1 / 50th of that of controls, and remained at this low level for the 34-week study. At best, said Lu, antiviral drugs reduce the viral load of less than five times and must be taken daily for life. the number of T cells in these monkeys have also increased to healthy numbers.

"It will be very important to follow these animals for a longer period," warns Bruce Walker, a biologist at Harvard Medical School in Boston. One of the "major obstacles" using the immunotherapy for the treatment of AIDS in humans, he said, is the constant area evolution of the virus due to its rapid mutation rate, allowing some viral variants slip past the immune system.

Related Sites
more on immunotherapy
more research on AIDS

Even after kicking the habit nicotine, ex-puffers scary side by side of getting lung cancer. But a new study offers hope that there might one day be a way to reverse the damage of smoking pack-a-day.

After the assault carcinogens in tobacco smoke, certain lung cells genetically damaged continue to survive and reproduce. The problems can accumulate with each new generation of cells, eventually causing lung cancer. Efforts to prevent lung cancer have focused on some of the early warning signals of the body. One of these flags is reduced expression of a gene called b retinoic acid (RAR b ), which normally contributes to regulating cell growth, differentiation and death. lungs damaged by smoke have fewer receptors for compounds called retinoids that stimulate RAR b expression.

Reasoning that a dose of retinoids could stimulate additional RAR b expression, oncologists Jonathan Kurie and Waun Ki Hong, University of Texas, Dallas, asked 177 former smokers to try two versions. One group was treated with a retinoid called 13-cis-RA, which has been successfully used to slow or prevent the regrowth of tumors of the head and neck. A second group was treated with 9-cis RA, a compound which can bind to many receivers retinoic.

The lung tissue sampled from the team before treatment and after 3 and 6 months. Those with 9-cis-RA showed a small but significant jump in RAR b term - from 69% to 76% of normal expression. There were a lot of bad news too, though. The RA-13-cis treatment was not significantly better than placebo treatment, and no treatment significantly reduces other signs of cancer such as changes in cell shape, arrangement and function. In addition, two retinoids caused severe muscle pain, fatigue and rashes, among other afflictions, the team reports in the February 5 Journal of the National Cancer Institute . Yet Kurie said he is encouraged by the results and think it will be possible to find drugs that stimulate RAR b production without the side effects.

"This is the first evidence that some damage can be reversed in former smokers," says cancer biologist Gregory Riggins Duke University in Durham, North Carolina. Riggins characterized the results as "quite attractive ", but warned that drugs that erase safely damage caused by years of smoking are still far away.

Related Sites
Jonathan Kurie website
the Waun Ki Hong site
site Gregory Riggins

Locking iron in brain cells may prevent Parkinson's disease, according to a new study. He noted that the prevention of cellular damage caused by iron, using either a naturally occurring protein or a drug iron binding, may slow the progression of the devastating disease. The problem is that the drug, when bound to iron, poisons nerve cells.

Parkinson's disease destroys nerve cells in a brain region called the substantia nigra, which results in jerky movements and tremors that characterize the disease. These neurons seem to deteriorate due to the damage produced by the oxidation of dopamine in the brain chemical. Iron, if not properly restrained in the cell, can accelerate the creation of destructive oxygen molecules. Patients with Parkinson's disease have more iron in their brains than people without the disease, but researchers have not been sure that the disease causes iron buildup or vice versa.

Neurobiologist Julie Andersen of the Buck Institute for Age Research in Novato, California, and colleagues studied two ways to bind iron bulk in the brains of mice with a Parkinson-like disorder . First, they injected mouse embryos with a human gene that encodes a binding protein ferritin iron called. They were designed so that the only cells Niger gene locus and the associated parts of the brain produce the protein. Fewer neurons crashed in mice than in untreated animals. Next, the team tested the effect of clioquinol drug, which binds iron and zinc. Researchers have shown to slow the progression of Alzheimer's disease. Mice given oral clioquinol lost less brain cells than mice that did not receive the drug. . Both ferritin and clioquinol treatments also kept the motor skills of the mice, the researchers report in March 27 number Neuron

Controversy surrounds clioquinol, however; the drug was banned after its use as an antibiotic seemed to cause a neurodegenerative disease in some Japanese patients. Andersen and colleagues suggest that vitamin B-12 deficiency caused toxic effects, and that give patients additional B-12 would eliminate the problem. Yet Jack Arbiser dermatologist at Emory University in Atlanta, Georgia, calls for caution. "They have never proven that B-12 is the issue," he said. Whether clioquinol proves to be useful, "this should certainly stimulate efforts to find ways to intervene in iron," says Alzheimer's disease researcher Gregory Cole of the University of California, Los Angeles.

related sites
Web site laboratory Julie Andersen
lab website Gregory Cole
NIH page of information on Parkinson's disease

For several years, cancer researchers have tried to develop therapies that work not by directly killing tumor cells, but by depriving them of the blood supply they need to live and grow. New results, published in the number of Science , 16 May should spur the field. The work suggests that tumor response to radiotherapy depend on the fact that the radiation kills the small blood vessels that feed the tumor. The finding may pave the way for better therapies for the treatment of cancers resistant to irradiation.

Researchers had thought that the radiation kills tumor cells directly. But 2 years ago, a team led by biologist Richard Kolesnick cancer and Zvi Fuks radiologist at Memorial Sloan Kettering Cancer Center, New York has shown that one of the main side effects of radiotherapy, damage to the gastrointestinal tract, occurs because the radiation induces apoptosis, a form of cell suicide, in the cells of small blood vessels, channels. They have also linked this to production apoptosis induced by radiation from a chemical called ceramide. They found that mice that do not make ceramide because they lack an enzyme called acid sphingomyelinase (asmase) are protected against damage. Fuks Kolesnick and then decided to see if the cells of the blood vessels of cancerous tumors are also vulnerable to radiation.

The current work shows that they are. transplanted tumors, for example, grow faster in mice in which the gene was knocked asmase than in normal mice. Tumors growth in engineered mice are also much more resistant to radiation, apparently because the cells of their blood vessels, unlike those tumors in normal mice, undergo little apoptosis in response to radiotherapy.

Cancer Center researcher Robert College Health Sciences Kerbel of the Sunnybrook and Women in Toronto researchers described the work as "elegant. using knockout strain of mice, they showed very conclusive proof of concept "that therapies that target tumor blood vessels can improve tumor responses to treatment. Kerbel also noted that the results link with the work of his group and others showing that something similar happens with cancer chemotherapy.

Fuks suggests that the results could improve radiotherapy. He stresses that cancers might be able to resist radiation because they dump factors that stimulate the growth of blood vessels, thus counteracting the apoptosis induced by radiation. It may be possible to improve the apoptosis of blood vessel cells, or with drugs that block the activity of factors or stimulating asmase activity.

A gene therapy can improve muscle shortcut. function in mice with a disease of muscular dystrophy, scientists have found. The trick is to inject an RNA molecule that can help eliminate the genetic mutation in muscle cells. This allows the gene to be translated into a functional protein reasonably.

Muscular dystrophy, a disease caused by a genetic mutation on the X chromosome, primarily affects boys and is available in several varieties. People suffering from Duchenne muscular dystrophy - one of the most severe types - CAN NOT produce dystrophin, the muscle protein; most die of heart failure or other problems in their early 20s Presentation of the normal dystrophin gene in the muscles could theoretically induce cells to produce dystrophin. But it is difficult because the dystrophin gene is huge and unwieldy.

In recent years, several teams began to test another approach. Like most genes, RNA dystrophin protein undergoes a process called splicing, in which extends the so-called "junk" are tailor. Researchers exploit this step by introducing a short stretch of RNA is the genetic mirror image of the Duchenne mutation. This RNA "antisense" binds to RNA molecules from the defective region; accordingly, the splicers interpret the change as junk and eliminate it. The result is an almost normal RNA. But although the method had obtained good results in Petri dishes, the approach did not work as well in animals.

Muscle biologists Qi Lu long and Terence Partridge in Clinical Sciences Centre Medical Research Council in London, UK, and colleagues decided to antisense strategy combined with a chemical often used in therapy gene because it is known to improve the delivery of DNA into cells. The group felt that it could do the same for RNA. When the combination was injected into a large muscle at the diseased mice, gave rise to dystrophin levels that were 20% of normal, compared to none in the controls. That was enough for the muscle to carry some weight, and injection product dystrophin for 3 months, the group reports in the online July 6 Nature Medicine.

"It is very encouraging," said neuroscientist Thomas Rando of Stanford University in California. The challenge now, he believes, is to provide antisense RNA in the blood, it becomes integrated into many muscles at once, and modify it to last longer.

Related Sites
Information on Muscular Dystrophy National Institutes of Health
research on muscular dystrophy Muscular Dystrophy Association

Chinese doctors prescribed for thousands of years, and even today it is one of the most effective treatments for malaria. Now, scientists say they have finally discovered exactly how a drug of plant origin called artemisinin kills malaria parasites. The discovery may help develop new weapons against malaria.

Artemisinin and several derivatives are derived from Qinghao, also known as mugwort or Artemisia annua , a long plant known for its antipyretic capacity. Qinghao extracts have recently become very popular in Southeast Asia, where resistance to most other drugs against malaria is endemic, and more and more researchers are studying drugs. But exactly how artemisinin kills the parasite Plasmodium falciparum that causes malaria remained uncertain. Artemisinin has a chemical structure called a bridge peroxide, which can be cleaved by iron ions to form free radicals that attack a range of proteins and other biomolecules; some researchers suspected that such an attack would be fatal for parasites. Others have speculated that, like chloroquine against malaria drug, artemisinin frustrates the removal of heme, a toxic by-product formed during the consumption of the parasite of human hemoglobin.

None of these explanations is correct, according to a team from the University of Liverpool, University of Southampton Medical School and Hospital of St. George in the UK the team noted that the chemical structure artemisinin resembles thapsigargin, an inhibitor of an enzyme present in mammalian cells. Maybe doing something like artemisinin, they reasoned - and of course, artemisinin has proven a powerful specific inhibitor and a similar enzyme, called PfATP6 in Plasmodium . A series of experiments confirmed that the drug's ability to block PfATP6 is also what thwarts the parasites.

"I think their data and I think they have a very strong argument," says molecular epidemiologist Steven Meshnick from the University of North Carolina, Chapel Hill. Yet he says he is not totally convinced yet; the ideal way to nail PfATP6 the goal of artemisinin would find a Plasmodium strain resistant to artemisinin and show that they have a mutation in the gene PfATP6 he said . So far, none of these resistant strains have been found in patients - and no hope to see soon

Related site
malaria information of World health organization

The quality of the neighborhood that motor neurons are in determines whether they are, a new study shows healthy or degenerate. own force inherited the motor neurons is not as important. The results reveal new approaches to therapies for amyotrophic lateral sclerosis (ALS), also known as the disease of Lou Gehrig.

ALS is a neurodegenerative disease in which people lose control of their muscles, which eventually atrophy. Researchers believe that the muscles fade after the motor neurons that innervate die. Although the majority of ALS cases arise spontaneously, about 2% are due to inherited mutations in the gene for superoxide dismutase (SOD1), an enzyme that scavenges free radicals that damage cells. When the mutant SOD1 is overproduced gene in mice, the animals suffer similar progressive neurodegeneration in ALS.

Scientists have long thought that the mutant SOD1 somehow mucks inside functioning motor neurons and kills them, but nobody has been able to prove it. Last year, a research group overexpressed mutant SOD1 in mice - only in motor neurons - but the mice showed no adverse effects. For monitoring, another team led by Don Cleveland at the University of California, San Diego, mice engineered with normal cells and cells with a mutant SOD1 gene to determine if the neighboring cells mutant contribute to neurodegeneration.

researchers found that the only time that motor neurons degenerate was when they were surrounded by mutant helper cells. The higher the percentage of patients helper cells, they report in the October issue 3 Science , plus neurodegeneration and the worst animal disease. However, when helper cells healthy surrounded SOD1 containing motor neurons, neurons are not dead - and the animals lived a normal life span. The researchers were unable to identify what types of helper cells were the most important, but these experiments are underway.

The work should lead to a "change of mentality for neurodegenerative diseases," because the focus has always been on the nerve cells themselves, says neuroscientist Jeffrey Rothstein of the medical school of the Johns Hopkins University. "It is equally important to consider the non-neuronal cells." neighboring cells could be targeted by stem cell therapies that seek to replace the cells carrying the mutation or by drug treatments to correct the defect . He said that the role of neighboring cells is surprising. " I presume they would be this important "

Related Sites
The site of Don Cleveland
Information on ALS NIH

For the second time since the outbreak of severe acute respiratory syndrome (SARS) was brought under control in July, a scientist who studies the virus accidentally infected with it. Early Wednesday morning local time, the tests confirmed that 44 Taiwanese researcher SARS, the Department of Health of Taiwan said today. So far it does not appear to have infected anyone else. But the case is a grim reminder, experts say, that the same researchers the fight against SARS could trigger the next global epidemic.

The new patient, lead researcher at the National Defense University in Taipei, came down with flu-like symptoms after returning from a scientific conference in Singapore on 10 December. Later, he also developed diarrhea. He was admitted to hospital on 16 December, where an X-ray revealed pneumonia in his right lung. reaction tests polymerase chain reaction showed the presence of the SARS coronavirus, the Ministry of Health says - a diagnosis that was confirmed at the Taiwan Center for Disease Control earlier today. The test will be repeated at the National Virology Institute in Tokyo, said Australian virologist John Mackenzie, who coordinates temporarily SARS research to the World Health Organization (WHO) in Geneva. In October, an informal network of SARS laboratories recommended that any new diagnosis of SARS will be confirmed in a laboratory in a different country.

Colleagues of patients and family members were invited to monitor their health for 14 days and will be isolated if they develop a fever, Taiwanese authorities said. The Singapore government went further, issuing a quarantine order for 70 people who were in contact with the researcher on 9 and 10 December. Patients who were on the same plane back to Singapore to Taipei on December 10 will be traced and told to watch for symptoms of SARS. In Beijing, the Chinese government said it is on alert.

The researcher studied the SARS since last June, and is believed to have contracted the disease in the laboratory before leaving for Singapore on December 7. The Taiwanese government inquiry into the circumstances. "We obviously need to know what is desperately arrived in this laboratory," says Mackenzie. Last August, a virologist of 27 who has studied the West Nile virus in the Environmental Health Institute in Singapore came down with the disease; an investigation blamed the infection on laboratory procedures sloppy laboratory ( Science NOW, September 23). The WHO has stressed the importance of strict biosecurity procedures and some form of certification for laboratories working with the virus. "This again confirms our fears," says Mackenzie.

Related Sites
Press release of the Department of Taiwan Health
WHO SARS information

Multiple sclerosis (MS) has long been considered an autoimmune disease. But new research suggests that it is not immune cells that strip the insulation off neurons and cause neurological symptoms. On the contrary, the insulation can be disturbed when cells that construct self-destruct.

In MS, the insulating layer of myelin around neurons degrades, which leads to loss of muscle control, numbness or cognitive problems. Most researchers thought that this happens when the own immune cells of the victim move on myelin and chew, leaving scars behind plaquelike.

Now, neurologists Michael Barnett and John Prineas the University of Sydney, Australia, have found evidence to the contrary. They autopsied 12 patients who died from MS shortly after suffering an episode of neurological symptoms. All patients had scars plaquelike typical of MS. But against all odds, seven of them were intact and little inflammation myelin, the researchers reported online this week in Annals of Neurology . Is also surprising that, in the plates until 30% of the cells which form the lining of myelin appeared to be suicidal. The researchers conclude that MS is triggered by an autoimmune insult, but rather by something - maybe a virus - which encourages cell suicide. In this scenario, the dead cells cause the immune response, and not the reverse.

"The MS field is so focused on autoimmunity as a cause that we rarely hear an alternative hypothesis," says cell biologist Bruce Trapp at the Cleveland Clinic Foundation in Ohio. The study is refreshing, he said, because "the pathology of MS can not be explained by what we know now." Experimental neuropathologist Moses Rodriguez of the Mayo Clinic in Rochester, New York, agrees that viruses are likely suspects. He said the result could explain why some anti-inflammatory drugs have not helped and why an antiviral drug, interferon, is one of the best treatments.

Related Sites
John Prineas website
National Multiple Sclerosis Society

WASHINGTON, DC - amyotrophic lateral sclerosis (ALS) Neurons havoc in the brain and spinal cord, often suffering in killing five years. But the diagnosis of the disease remains a major challenge. Now a pilot study presented here April 18 at the Federation of Associations for the Experimental Biology meeting identified 10 proteins that can distinguish ALS patients from healthy individuals.

Doctors lacking "biomarkers" with which definitively identify ALS patients. Biomarkers are proteins or other molecules that may help diagnose or monitor the progression of the disease; an example is the specific antigen of the prostate, the biological marker used to detect prostate cancer. Without ALS biomarkers, doctors and patients can not be certain that the defining symptoms such as muscle weakness and speech problems appear. This can delay treatment or lead to misdiagnosis.

pathologist Robert Bowser of the University of Pittsburgh in Pennsylvania and colleagues decided to hunt for biomarkers of ALS in the cerebrospinal fluid, which is in intimate contact with neurons and the glial cells ALS destroys cells. They collected samples of 25 ALS patients, who on average had had symptoms for about a year, and 35 controls. About half of the controls were healthy; the other half were diseases, including Alzheimer disease and neuropathies, which sometimes show symptoms of ALS-like.

By analyzing exhaustively sample protein, the Bowser team found 10 proteins whose levels were consistently higher or lower than those of control. The group then discussed a separate set of 32 samples, including 15 from ALS patients, without knowing which samples were from patients with ALS and which are not. Using an algorithm that they designed to distinguish the biomarker models, they correctly identified 12 of the 15 samples from ALS and an even higher percentage of orders. Besides early diagnosis, Bowser hopes that its biomarker will shed light on the disease; at least one of the proteins in a grave way that ALS destroyed.

"It's very exciting," said Lucie Bruijn, science director of the ALS Association. But she cautions that the results are preliminary. The association recently gave Bowser money for a larger study, to see if biomarkers fit in a larger population.

Related Sites
the homepage of Robert Bowser
the ALS Association
ALS Therapy Development Foundation

The most common form of Alzheimer's disease is not hereditary, and little is known about its causes. Now researchers have found a handful of genetic mutations that occur more frequently in patients with the disease. The results reinforce earlier suggestions that Alzheimer's is caused in part by deficits in energy cell power plants.

The researchers found some of the genes involved in familial Alzheimer's disease, accounting for about 10% of cases and usually strikes people in their 60s, but they have had little success finding genetic glitches associated with the most common form of late-onset. Some evidence indicated an ongoing accumulation of mutations in the DNA in mitochondria, the cells inside the energy-producing organelles. For example, Douglas Wallace, now at the University of California, Irvine, and colleagues found that a small percentage of patients with Alzheimer carried a specific mutation in their mitochondrial DNA. But it simply could not explain the large number of late-onset victims. So they kept looking.

After reviewing each mitochondrial gene that encodes a protein, without success, Wallace's team decided to test the changes in a short DNA region that regulates the expression of mitochondrial genes and helps copy mitochondrial DNA when cells divide. By comparing the DNA of the brains of 23 Alzheimer's patients brains against 40 healthy age-matched, the team found a mutation that occurred exclusively in the brain of Alzheimer's - 65% of diseased brains contained this mutation the reports online this week in the team Proceedings of the national Academy of sciences . Other mutations were also more common in patients with Alzheimer's. In addition, the team found that the brains of people who died of Alzheimer's disease before 80 years harbored few mutations in many cells, whereas those who died later brought a greater variety of mutations in less cells. This suggests that the mutations that occur early in life and accumulate in brain cells may increase the risk of disease.

The mutant mitochondrial DNA the team found "are worth," says Rudolph Tanzi neurogeneticist of Harvard Medical School in Boston. But, although the data are consistent with other evidence linking mitochondria to Alzheimer's disease, he warned that the sample size of the study is so small that the results should be considered preliminary.

related site
genetic information of Alzheimer's disease

anger is often spoken of as a disease; he fumed or festers and becomes inflamed. Now it seems that these terms can have a scientific basis in fact. A new study, angry people have high levels of a protein linked to inflammation, which may partly explain the higher risk of cardiovascular disease in the blood.

As the role of inflammation in heart disease emerged, scientists have found high levels of C-reactive protein (CRP) is a better indicator than high cholesterol cardiovascular disease. High CRP levels are also associated with depression. In addition, studies have shown that individuals angry (formerly known as "type A") or depression are at a higher risk of heart disease and stroke.

Psychiatry Professor Edward Suarez at Duke University brought together all these son studying anger, hostility, depression and CRP levels in 127 healthy elderly adults 18 and 65. He given all three test subjects: an inventory of depression on the scale of anger (measuring the emotional aspects of anger), and a scale of hostility (measuring attitudes such as ill will and perception of resentment). CRP levels were measured after overnight fasting.People with full infusion of negative emotions had CRP levels two to three times higher than the quieter subjects, more optimistic, says Suarez in the number of the month of Psychosomatic Medicine . The study adds to an emerging picture of how the changes induced by stress in the nervous system can trigger the immune system. The inflammatory responses rough lining of the arteries, making them more prone to accumulate plaque.Psychologist Janice Kiecolt-Glaser of Ohio State University in Columbus, who does research on emotions and disease, said the study provides " the first evidence linking CRP with anger and hostility. "But Marco Pahor, gerontologist at Wake Forest University Baptist Medical Center in Winston-Salem, North Carolina, says the study does not prove cause and effect, and notes that further work is needed to determine if psychological factors contribute to inflammation-related disease.

Related Sites
research on emotions and heart disease

estrogen and the COX-2 enzyme have more in common than their ability to generate excitement marred by controversy. It happens that we recruit the other blood vessels in mice. The work suggests that COX-2 inhibitors may be more dangerous for women than men and may help explain how the production of estrogen in premenopausal women has the heart.

COX-2 and estrogen both impact the cardiovascular system, although scientists are still sorting out their precise effects. Estrogen is thought to explain why premenopausal women, churning much of the hormone, are less likely to have heart disease than men. But 2 years ago, Initiative on Women's Health reported that older women who take hormone supplements had more, not less, heart problems than women on placebo. As COX-2, in late September, pharmaceutical giant Merck pulled its COX-2 inhibitor Vioxx from the market after a study showed that patients taking Vioxx suffered more heart attacks.

Garret FitzGerald, a pharmacologist and cardiologist at the University of Pennsylvania and a critic of COX-2 inhibitors, was curious about a fatty acid called prostacyclin, which is produced by COX-2. Cardiologists consider the loss of prostacyclin a likely culprit behind the misfortunes of Vioxx ( Science , 15 October, p. 384). The group FitzGerald created genetically susceptible to atherosclerosis and mouse receptor without the prostacyclin. In these animals, there was no gender gap in heart disease and female mice were highly susceptible to oxidative damage from free radicals that stimulate the formation of plaque in the arteries. Next, the team sought to make estrogen in the image, turning to mice whose ovaries were removed and received estrogen supplement. The supplements increased prostacyclin biosynthesis and depressed oxidative stress, the team reports online today in Science . This suggests that in premenopausal women, estrogen stimulates COX-2 production. This stimulates prostacyclin and protects against atherosclerosis, said FitzGerald. Because this route leads would be much lower estrogen in men, the work may also explain the gender gap in heart disease and suggest that women who use COX-2 inhibitors may be at greater risk for atherosclerosis that men, says FitzGerald.

"[This study] opens a new option for reassessing phenomena we have been wondering about for decades," says Kay Brown, a pharmacologist at the University of Erlangen in Germany. Although he and other cautioned about extrapolating the results to humans, Brunette nevertheless called it "potentially enormous clinical significance."

Related site
The Science Document