Naked Science Forum
Life Sciences => Physiology & Medicine => Topic started by: NakedScientist on 09/04/2003 17:20:35
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Below are the latest medical discoveries announced on the world-stage
This topic is for information only and hence you cannot reply to any of the stories contained here. Please feel free, however, to start a fresh thread related to anything you read here.
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A CHOLESTEROL-CONTROLLING DRUG COULD STRIKE A BLOW AGAINST INSULIN RESISTANCE
Type 2 diabetes is now an epidemic. Simvastatin could be key for prevention against this deadly disease.
April 9, 2003 (San Diego, CA) -- In industrialized countries insulin resistance/diabetes have become major public health concerns because of their epidemic growth and their association with major cardiovascular risk factors that are responsible for excess morbidity and mortality. In 1999, Americans had a six percent increase in new patients with Type 2 diabetes; growing obesity rates and sedentary lifestyles are also taking their toll across the Atlantic where Type 2 diabetes currently afflicts 22.5 million Europeans -- a staggering five percent of the population -- with another six million cases expected by 2025.
Researchers are looking for underlying mechanisms and new ways to combat this epidemic. Over the past decade, evidence has accumulated indicating that nitric oxide (NO) may play a key role in the control of metabolic and cardiovascular homeostasis, as evidenced by mice lacking the gene for endothelial nitric oxide synthase (eNOS) that are insulin resistant and hypertensive. An animal study now finds that stimulating NO bioavailability by lipid lowering statins may represent a new way to combat this epidemic.
Statins are a group of compounds that have been used successfully to lower cholesterol and prevent myocardial infarction. A less well known effect of statins is that they augment NO bioavailability in circulation. Abnormalities in the body's production of NO have been implicated in high blood pressure, atherosclerosis (narrowing of the arteries), diabetes, impotence, and stroke.
One statin is the prescription drug Simvastatin, used with diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and certain fatty substances in the blood. Accumulation of cholesterol and fats along the walls of the arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to the heart, brain, and other parts of the body. Lowering your blood level of cholesterol and fats may help to prevent heart disease, angina (chest pain), strokes, and heart attacks. Now this important drug could also be instrumental in the battle against insulin resistance.
The role of stimulating NO bioavailability by statins in treating insulin resistance is addressed in a study from Switzerland. The authors of " Simvastatin Prevents High-Fat Diet-Diet-Induced Arterial Hypertension and Metabolic Insulin Resistance in Partially eNOS Deficient Mice," are Stephane Cook, MD, Peter Vollenweider, MD and Urs Scherrer, MD, all at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Their findings are being presented at the American Physiology Society sponsored conference, Experimental Biology 2003, being held April 11-15, 2003, at the San Diego Conference Center, San Diego, CA.
Methodology
Simvastatin or vehicle treated eNOS+/- and eNOS-/- mice were fed a high-fat diet or normal chow for eight weeks. Arterial pressure and insulin sensitivity (glucose infusion rate during euglycemic hyperinsulinemic clamp) were measured at the end of this eight week period.
Results
High-fat diet caused arterial hypertension and insulin resistance in eNOS+/- mice. Simvastatin prevented both the high-fat diet-induced insulin resistance and arterial hypertension in eNOS+/- mice. In contrast, simvastatin did not attenuate high-fat diet induced arterial hypertension and insulin resistance in eNOS-/- mice.
Conclusions
These findings provide the first evidence that simvastatin prevents diet-induced arterial hypertension and insulin resistance in mice. This effect appears to be related to stimulation of vascular NO availability (as evidenced by the results in eNOS-/- mice). These data suggest that simvastatin may help to combat the epidemic of insulin resistance and hypertension in humans.
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SCIENTISTS FIND GENETIC KEY TO TB SURVIVAL IN LUNGS
By LESLIE H. LANG
UNC School of Medicine
CHAPEL HILL -- New research led by a University of North Carolina at Chapel Hill scientist shows for the first time how Mycobacterium tuberculosis, the germ responsible for TB, uses a system for releasing proteins to help it survive the lungs' immune defenses to spread and cause disease.
The study, published online in the April issue of Molecular Microbiology, also adds crucial new knowledge to the molecular factors that underlie the virulence of M. tuberculosis and may aid development of new, targeted treatments for the disease.
"I think this study moves us along in our understanding of TB pathogenesis," said study lead author Dr. Miriam Braunstein, assistant professor of microbiology and immunology at UNC's School of Medicine.
In 2003, 10 years after the World Health Organization declared tuberculosis a global emergency, tuberculosis remains a severe worldwide health threat. More people die from the disease than from any other curable infectious disease. TB kills approximately 2 million people every year, 98 percent in developing countries. One-third of the world's population is infected with the TB bacillus.
In the report, Braunstein and co-authors Drs. William R. Jacobs Jr. and John Chan from New York's Albert Einstein College of Medicine, and Drs. Benjamin Espinosa and John T. Belisle from Colorado State University said numerous disease-causing bacteria "possess specialized protein secretion systems that are dedicated to the export of virulence factors."
The TB bacillus possesses in its genome the genes secA1 and secA2, the researchers said. In a previous report, Braunstein and others had shown that the protein SecA1 is essential for the bacillus, whereas SecA2 is not. Both of these proteins are similar to SecA, a protein that functions in the secretion process of all other bacteria.
However, the presence of multiple SecA proteins in a single bacterium is highly unusual and only shared with a few other pathogenic bacteria.
"In this study, we wanted to see if the two SecAs do the same thing or have different functions. We had a hunch that SecA2 was involved in the bacteria's virulence, that it might be dedicated to secreting a specific subset of proteins involved in virulence," Braunstein said.
To test that hypothesis, she and her colleagues genetically engineered a mutant strain of M. tuberculosis that did not have secA2. This gene deletion meant it could not produce the protein SecA2.
"We tested the strain for virulence by infecting mice with it and observed how long the mice survived over time," Braunstein said. "And we found that the mice infected with mutant TB survived longer than 'wild-type' mice infected with TB having a functioning secA2 gene. This told us the mutant strain was not as virulent."
To further examine virulence, the researchers also examined the extent of bacterial growth in the lung, liver and spleen. "Those experiments showed the same thing," she said. "When TB is missing SecA2, it is less virulent. There is less bacterial growth, particularly in the lung."
Having demonstrated that SecA2 is required for virulence, the next step was to identify the virulence factor secreted by the protein. Two of the proteins dependent on SecA2 that were identified were antioxidant molecules: superoxide dismutase-A and catalase-peroxidase.
When M. tuberculosis is inhaled and enters the lungs via the small air sacs called alveoli, the bacteria becomes aggressively attacked and engulfed by macrophages, immune system scavenger cells. But where other bacteria succumb to the attack, TB survives in macrophage, having evolved over the millennia a mechanism to overcome the "oxidative burst" leveled at it.
"These SecA2-dependent secretions, superoxide dismutase and catalase-peroxidase are enzymes that actually scavenge the oxygen radicals that are shot at the bacteria," Braunstein said.
"All mycobacteria strains, including TB, appear to have two secA genes. So I think a long time ago the gene duplicated benignly, but one of those secAs evolved to provide a protective advantage for the pathogen. That's why it's still there and important to pathogen survival in macrophages."
Thus, according to the researcher, the two enzymes secreted by secA2 act as virulence factors contributing to TB's defense against destruction in the macrophage.
Moreover, this newly described virulence mechanism may apply to other types of disease-causing bacteria.
"In the last year or so, a number of Gram-positive bacterial pathogens have been identified that have two SecA proteins," Braunstein said.
Important Gram-positive pathogens with two SecAs include Listeria monocytogenes, Staphylococcus aureus and Streptococcus pneumoniae. "Gram-positive" refers to the grouping of bacteria relating to its outer structure.
"In some it has already been shown that the extra secA2 gene is required for virulence. So it might be common to certain bacterial pathogens."
Someday, drugs against TB infection could be developed aimed at blocking this secretion system, Braunstein said. "For now, the results of this study offer some new and important insights into the pathogenesis of this serious health threat."
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NEW APPROACH TO THE TREATMENT OF CHILDHOOD ECZEMA ADVOCATED BY US DERMATOLOGISTS
Eczema, an itchy rash that affects large numbers of infants and children, should be treated in a new way, according to a new paper outlining best treatments for the disease.
The new approach urges physicians to focus on giving patients the best possible long-term management of eczema, also known as atopic dermatitis, using a combination of older and newer types of treatment.
Previous management of the disease focused on treating acute attacks with short courses of corticosteroid creams. Now, a team of doctors co-led by a University of Michigan dermatologist say that new medications, known as calcineurin inhibitors, should be used to help relieve symptoms over the long term. The new medicated creams turn off specific inflammatory cells in the skin that cause the redness and broken skin that are the hallmarks of eczema in young children.
In a paper published today in the May issue of the British Journal of Dermatology, the team describes a new approach to treatment that was adopted at the 2nd International Consensus Conference on Atopic Dermatitis by experts from 10 countries in Europe and the Americas. The conference was sponsored by a grant from Novartis Pharmaceuticals, which makes a calcineurin inhibitor medication.
U-M Health System dermatologist Charles Ellis, M.D., co-author of the new paper, explained that safety concerns have led to restrictions on the intensity and duration of topical corticosteroid use, especially in children and on delicate areas such as the face, neck and skin folds. As a result, many patients endure their eczema's pain and itching aided only by standard over-the-counter lotions.
"A new consensus approach is needed to ensure patients can get the best treatment, including the new therapies such as topical calcineurin inhibitors, and see how these might be used in a coordinated way to improve long-term symptom control while minimizing safety concerns," says Ellis, professor and associate chair of the Department of Dermatology at the University of Michigan Medical School.
Ellis and his fellow clinicians concluded that:
* safe, effective therapy is needed for long-term maintenance of atopic dermatitis in patients of all ages
* topical corticosteroids are effective, but provoke concerns over their safety for long-term use
* the new class of topical calcineurin inhibitors may offer a solution to these concerns by providing a safe and effective treatment for the long-term control of atopic dermatitis. These drugs are non-steroid, selective cytokine inhibitors that do not cause the skin atrophy, blood vessel growth, glaucoma or growth retardation associated with corticosteroids
The Consensus Conference resulted in a comprehensive treatment algorithm that considers how all the key treatments for atopic dermatitis, including emollients (lotions), topical corticosteroids, topical calcineurin inhibitors, phototherapy and oral cyclosporine, can be used to greatest effect at the various stages of the condition.
"All of these treatments have an important place in the effective management of atopic dermatitis. But we should be using new and emerging therapies to complement our more traditional approaches," points out Ellis' co-chair, Thomas Luger, from the Department of Dermatology at the University of Munster, Germany.
"For example, topical calcineurin inhibitors could be used for maintenance therapy because they have been shown both to prevent disease progression and to reduce the incidence of flares. Calcineurin inhibitors could be used at the first signs and symptoms of atopic dermatitis and be used for as long as these persist, while corticosteroids could be reserved for the treatment of severe exacerbations," he adds.
Atopic dermatitis affects 10 percent to 15 percent of children under five years of age in developed countries, and its prevalence is rising. It is a chronic disease characterized by intense itching and recurrent flares. At present, there is no cure.
The ICCAD II framework defines the key aims of treatment as:
* reduce acute signs and symptoms
* prevent or reduce recurrences
* provide long-term management by preventing flares
* modify the course of the disease
Ellis welcomes the comprehensive approach of the new treatment concept in treating all stages of atopic dermatitis. "This can be a very distressing and debilitating condition for patients and their families. In the past we have tended to focus on reactive treatment for relapses and we may not have paid enough attention to long-term maintenance treatment aimed at preventing recurrences and flares," he says.
"These new guidelines remind us that we have a lot of highly effective treatments at our disposal to help all our patients whatever the severity of their disease," he adds.
The guidelines recommend:
* continuing use of emollients and education, with trigger avoidance and other adjunctive therapy as appropriate
* topical corticosteroids or topical calcineurin inhibitors for acute control of itching and inflammation
* for maintenance therapy (persistent disease and/or frequent recurrences), calcineurin inhibitors to prevent disease progression, and intermittent use of topical corticosteroids
* for severe refractory disease -- phototherapy, potent topical steroids, oral cyclosporine, methotrexate, oral corticosteroids, azathioprine, and other therapies
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CLONING HUMANS MAY NOT BE POSSIBLE, SAYS NEW RESEARCH
http://bmj.com/cgi/content/full/326/7394/838/c
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POTENTIAL 'TARGET' FOR ANTI-OBESITY DRUGS TO AIM AT...
Salk Researchers Find Receptor That Controls Obesity
La Jolla, Calif.--A cellular receptor that balances the accumulation of fat and fat burning in the body may be a new target for anti-obesity and cholesterol-fighting drugs, according to a Salk Institute study.
The study, published in the April 18 issue of Cell, identified the function of this key receptor for the first time. The receptor, called PPARd, was found to regulate how fat is used and could point the way to new treatments for obesity as well as its associated lethal medical complications: type II diabetes, cardiovascular disease, hypertension and atherosclerosis.
Professor Ronald M. Evans, the March of Dimes Chair in Developmental and Molecular Biology at the Salk Institute and Howard Hughes Medical Institute investigator, and his team found that stimulating PPARd -- short for peroxisome proliferators-activated receptor -- depleted fat deposits in mice, while mice deficient in PPARd were prone to obesity.
PPARd was shown to regulate the rate by which fat is burned to produce heat or is used to maintain normal cell functions. The process of uncoupling energy from work production to heat generation, known as adaptive thermogenesis, is generally regarded as a physiological defense against obesity.
"We have long known that excess calories are warehoused in fat tissue for future use," said Evans. "We also know that fat is released and consumed in times when energy is needed, such as from exercise or shivering from cold exposure. This study shows us that PPARd is an important regulator of this function. By exploiting PPARd, we hope to design drugs that can control how much fat is stored in the body."
The team found that mice with an activated PPARd gene weighed about 20 percent less than normal mice, even though both groups received the same food at the same rate. Once the mice were a year old, the difference in weight widened, to 35 percent less for the genetically active PPARd mice.
At the same time, activated PPARd protects mice against diet-induced obesity. Mice that had the active PPARd gene did not show significant weight gain over a month's time, despite having a high-calorie, high-fat diet. Mice without the active gene, however, became obese. In addition, a short-term treatment of the obese mice with a molecule that activated PPARd caused a dramatic reduction in fat in their tissues.
"PPARd activates an array of genes that are required for fatty acid combustion and uncoupling, but does not activate genes that are involved in the formation and storage of fats," said Evans. "We show then, that PPARd coordinates fatty acid oxidation (burning) and energy uncoupling to regulate the use of fat."
Obesity is now considered an epidemic in the United States. About 65 percent of Americans are considered overweight, and some states report an obesity rate of over 20 percent of their populations. The condition is strongly linked to some of the leading causes of death in the United States, including high blood pressure, heart disease and diabetes. Deaths due to overweight conditions kill more than 300,000 people a year, second only to tobacco-related diseases, according to the U.S. Centers for Disease Control.
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A NEW WAY TO TARGET CANCER CELLS
Compound Triggers Release of Nitric Oxide to Fight Leukaemia and Tumours
April 14, 2003 - Researchers from the University of Utah and the National Cancer Institute developed an experimental drug that reacts with a substance inside cancer cells, releasing nitric oxide to kill the cells or slow their growth without harming healthy cells.
Tests showed the drug, called JS-K, induced the cell-suicide process in acute myeloid leukaemia (AML) cells grown in culture and inhibited their growth in mice. AML is the most common and most deadly form of leukaemia. In other tests on cell cultures, the drug also inhibited growth of AML cells and - to a lesser extent - prostate, colon and breast cancer cells. It also inhibited growth of prostate cancer cells in mice.
"If all goes well, this would be the first cancer chemotherapeutic agent based on selective delivery of nitric oxide to tumour cells and therefore would constitute a novel class of cancer drugs," said physician Paul Shami, an associate professor of medical oncology at the University of Utah School of Medicine, member of the university's Huntsman Cancer Institute and chief of haematology-oncology at the Salt Lake City Veterans Affairs Medical Center. "It looks promising in cell culture and mice, but much work needs to be done before we know if it can be used in humans for the treatment of cancer."
Nitric oxide is distinct from nitrous oxide or "laughing gas," which is used as a dental anaesthetic. Nitric oxide in sufficiently large concentrations is toxic to cells, and it can cause dangerously low blood pressure. Yet it is found naturally in the body and helps control blood pressure. Nitric oxide also is released in response to sexual stimulation, triggering a series of chemical steps that increase blood flow to the penis and produce an erection. The anti-impotence drug Viagra works by enhancing nitric oxide's effects, specifically by inhibiting activity of a substance that works against nitric oxide.
The new study was published in the April issue of the journal Molecular Cancer Therapeutics. It was conducted by 14 scientists, led by Shami and by Larry K. Keefer of the National Cancer Institute (NCI) in Frederick, Md. Lai Y. Wang, a senior lab specialist at the University of Utah, assisted Shami. Other coauthors are from various branches of the NCI and from the University of Pittsburgh and George Mason University in Fairfax, Va.
Shami, who treats leukaemias and other cancers in adults, cautioned that even if all goes well, JS-K will not undergo initial safety and efficacy trials in human leukaemia patients until at least 2005, and that "to get to where your community physician will be able to prescribe it is maybe five years away, assuming everything goes according to plan."
He also said: "We have not done any formal animal toxicology studies, so we don't know the full side effects. One thing of primary concern to us is the effect on blood pressure. At the doses we've used to treat cancer in mice, it did not induce low blood pressure, but if and when it gets into human trials, we'll have to look at whether it induces low blood pressure. And we'll look at what it does to normal bone marrow cells and other normal cells."
The Study
Previous studies by Shami, Brice Weinberg at Duke University and colleagues showed nitric oxide inhibits growth and induces cell suicide among acute myeloid leukaemia cells grown in culture. In the new study, the researchers tested compounds that would trigger the release of nitric oxide inside cancer cells.
Shami and Wang tested in cell culture and sometimes in mice some 50 compounds designed to trigger nitric oxide release, and found JS-K was the most active. The compounds were sent to them by the researchers at NCI, where JS-K was synthesized by study coauthor Joseph Saavedra. It is named for his initials and is letter K in a series of compounds he synthesized. JS-K's chemical name is O2-(2,4-Dinitrophenyl) 1-[4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate. (Note: The 2 after the initial O should be superscript.)
In a key experiment, acute myeloid leukaemia cells known as HL-60 cells were implanted under the skin of mice that had suppressed immune systems and could not naturally combat the cancer cells, which grew to produce tumours. After 16 days of treatment with JS-K, the volume of the tumours was less than half the tumour volume in untreated mice. The treated mice did not suffer significant low blood pressure.
When the AML cells were grown in culture flasks, three days of treatment with JS-K caused the rate of cell suicide (called apoptosis) to increase from 7 percent without treatment to 27 percent and 43 percent, respectively, with two different concentrations of JS-K.
"This is in the league of currently available chemotherapeutic agents for this and other cancers," Shami said.
He said further experiments might find some other compound that works like JS-K but is more effective, more soluble or easier to use, so JS-K is considered a "lead compound" for further study and not necessarily a future chemotherapy drug.
How JS-K Works
JS-K is designed to react with natural enzymes called glutathione S-transferases, or GSTs, which help pump foreign substances out of certain cells. GSTs help the liver get rid of toxic substances in blood. But they also help cancer cells resist chemotherapy drugs. When GSTs in cancer cells interact with JS-K, there are two anticancer effects: GST activity is inhibited, making the cells less resistant to chemotherapy drugs, and nitric oxide is released.
"You have delivered nitric oxide inside your target cancer cell, and the nitric oxide will kill it," Shami said. "Other cancer-killing mechanism also may be occurring, and more work is needed to define them."
Much less GST is found in healthy cells compared with cancer cells, so researchers hope the reaction of GST with JS-K to release nitric oxide will occur to a much greater extent in cancer cells without harming healthy cells.
Acute Myeloid Leukaemia
Acute myeloid or myelogenous leukaemia (AML) is the most common and most deadly form of leukaemia, with 10,600 new cases diagnosed in the United States in 2002, according to "The Leukemia & Lymphoma Society" booklet Facts 2002. Only 19 percent of patients overall - and 46 percent of childhood AML patients - survive five years or more, the group says. That illustrates the need for new drugs to treat AML.
In AML, bone marrow cells called myeloblasts become cancerous instead of developing normally into white blood cells called neutrophils and monocytes. The cancerous cells build up in the bone marrow, which then fails to make enough normal blood cells, causing weakness, shortness of breath, bleeding, fever, vulnerability to infection and other symptoms. The cancerous cells can spread to other organs. Death can come from infection or from bleeding due to lack of adequate platelets.
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NEW PERMANENT BIRTH CONTROL OPTION FOR WOMEN OFFERS LESS-INVASIVE ALTERNATIVE TO TUBAL LIGATION
Couples looking for permanent contraception now have a new option other than tubal ligation or vasectomy. Doctors at the University of Maryland Medical Center are among the first in the area to offer Essure, a non-surgical procedure for women that involves placing small coils in the fallopian tubes. Over time, scar tissue develops around these coils, which blocks the fallopian tubes and prevents conception.
"This procedure will revolutionize permanent birth control because it is less invasive than tubal ligation or vasectomy," says Richard Marvel, M.D., a gynaecologist at the University of Maryland Medical Centre and an assistant professor of obstetrics, gynaecology and reproductive sciences at the University of Maryland School of Medicine. "What's so exciting about this procedure is that you don't need to make any incision. After the procedure, patients can go home or even go back to work."
While a tubal ligation requires general anaesthesia, the Essure procedure is done with local anaesthetic. During the procedure, doctors use a thin, telescope-type instrument called a hysteroscope and insert it through the cervix to reach the fallopian tubes. A camera on the end of the scope allows them to see into the uterus. Doctors place a small, soft coil in the fallopian tube, where it expands and fills the tube. Doctors then move to the other side to place another coil in the other tube. The entire procedure takes less than 30 minutes.
While the procedure itself is quick, it takes longer for the scar tissue to develop and permanently block the tubes. Women must use another form of contraception for at least three months. They also need to return 12 weeks after the procedure to have a special x-ray to confirm that the tubes are closed.
"Studies of the procedure have found that at three months, 96 percent of the women's tubes were closed and 100 percent were closed at six months," explains Dr. Marvel. In clinical trials involving more than 600 women, there were no pregnancies following the procedure. As with other birth control methods, the Essure system is not expected to be 100 percent effective; however the manufacturer cites a 99.8 percent effectiveness rate in two years of follow up.
Tubal ligation remains the most popular form of contraception in the United States with an estimated 700,000 procedures every year. The procedure involves cutting, sealing, or placing bands or clips around the fallopian tubes. Each operation requires cutting into the abdomen and a four to six day recovery period. Even laproscopic surgery with just small incisions carries a small risk of damage to the bowel, bladder, blood vessels and nerves. Many women express concerns about tubal ligation because of the anaesthesia, the incision and recovery time.
The new Essure method, which received FDA approval in November 2002, provides a less-invasive alternative for these women: there's no incision and it will eventually be performed in a doctor's office. Costs will likely be the same as a tubal ligation, and most insurance companies will cover the procedure as they do with other sterilization procedures for both women and men.
For couples considering vasectomy as a form of permanent birth control, Essure may be considered a less-invasive alternative because it does not require an incision. More than 400,000 men have a vasectomy each year in the United States. During a vasectomy, doctors clamp, cut or seal off each vas deferens tube (the tube through which sperm passes) in order to prevent the release of sperm.
Women who choose the Essure system must understand that it is irreversible, so they need to be certain in their decision to have permanent contraception. Essure does not protect against HIV and other sexually transmitted diseases. It will not affect menstruation or menopause.
"I honestly think Essure will revolutionize permanent contraception for women," says Dr. Marvel. "This is a procedure that can be done in an office setting in under 30 minutes using local anaesthesia without an incision."
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SEVERE FORM OF BIPOLAR DISORDER EASES SEARCH FOR DISEASE GENES
After years of searching for genes that contribute to mental illness, researchers at Johns Hopkins studying families with a severe form of manic depressive illness, called psychotic bipolar disorder, may be one step closer to finding the genetic underpinnings of both bipolar disorder and schizophrenia.
"Finding a gene for bipolar disorder is like finding a needle in a haystack, but by focusing our search on families with a distinctive form of the illness we were able to pinpoint a region of the genome where disease genes are likely to be found," says James Potash, M.D., assistant professor of psychiatry at Johns Hopkins and lead author of a report on the study in the April issue of the American Journal of Psychiatry.
Because certain broad regions of the DNA sequence, especially on human chromosomes 13 and 22, may contain genes that contribute to both bipolar disorder and schizophrenia, Potash and colleagues focused on families with the psychotic form of bipolar disorder. Psychotic bipolar disorder has psychotic symptoms such as hallucinations and delusions often accompanying the seesawing episodes of depression and mania that alone characterize bipolar disorder.
The researchers carefully evaluated and took blood samples from 65 patients with bipolar disorder and from their extended families. Out of 65 bipolar disorder families studied, the 10 families in which three or more members had psychotic bipolar disorder showed strong genetic "linkage" to specific regions on chromosomes 13 and 22.
"These results confirmed our expectation that genes for the psychotic form of bipolar disorder are likely to be found in the same regions that show linkage to both bipolar disorder as a whole and to schizophrenia," says Potash.
One important implication of the study is that these "overlap genes" may contribute to brain abnormalities that are shared by bipolar disorder and schizophrenia, and could help explain why the same antipsychotic medications are effective treatments for both diseases, says Potash.
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CERVICAL SCREENING IS WORKING WELL,
BUT IS LABOUR INTENSIVE
(Outcomes of screening to prevent cancer: analysis of cumulative incidence of cervical abnormality and modelling of cases and deaths prevented) http://bmj.com/cgi/content/full/326/7395/901
The NHS cervical screening programme is working well and preventing deaths, but is labour and resource intensive - around 1,000 women need to be screened for 35 years to prevent one death, say researchers in this week's BMJ.
Dr Angela Raffle and colleagues analysed the screening records of 350,000 women over 20 years and modelled cases of cervical cancer and deaths with and without screening.
Their results suggest that 8 out of every 10 women with "high grade" cell change will not go on to develop cancer, but all need to be treated.
For each death prevented at least 150 women have abnormal test results, over 80 women are referred to specialist clinics for investigation, and over 50 have treatment. At least one woman will die of cervical cancer despite participating in screening.
These findings have important implications, say the authors. For instance, even women who receive results of borderline changes can become anxious about their risk of cancer, so it is essential to change people's perception of the meaning of an abnormal screening
result.
Furthermore, because of the resources involved and the potential to do harm, it is in the public's interest to control the introduction of cancer screening programmes that have not been adequately evaluated or quality assured, they conclude.
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ASPIRIN FOR EVERYONE ?
ANN ARBOR, MI -- There seems to be a lot of new attention focused on good ole' fashioned aspirin, so much so that it's recently been touted as a 'wonder drug.' Evidence is rapidly growing that supports aspirin's use in lowering the rates of heart attack, stroke, colon cancer and even Alzheimer's disease. Given its widespread benefits and extremely low cost, the question is raised, "is daily aspirin therapy for everyone?"
"Although taking aspirin leads to a wealth of potential health benefits for adults, people should realize that even a baby aspirin is not free of dangerous side effects," says A. Mark Fendrick, M.D., an internist at the U-M Health System. "Therefore, in my opinion, aspirin should not be taken on a daily basis without first discussing it with your health care provider.
According to Fendrick, aspirin use should be based on the tradeoff between the risk of disease you are trying to prevent, such as a heart attack, and the risk of side effects, such as a bleeding ulcer. "Most consumers are not aware of this tradeoff," he says.
Aspirin falls into a drug class called non-steroidal anti-inflammatory drugs or NSAIDs. It's one of the most carefully studied drugs available and has been used to reduce pain and inflammation for over a century. Aspirin's action as a blood thinner saves a large number of deaths from heart disease each year.
"I think aspirin is currently undergoing a bit of an identity crisis," says Fendrick. "Because it's been around so long and is available over the counter for pennies a day, many people can't believe that aspirin is equally or more effective than prescription drugs that cost over a hundred times more."
Living up to its reputation as a 'wonder drug', aspirin has been shown in clinical studies to reduce the rate of heart attacks, strokes and related deaths. The ability of aspirin to prevent blood from clotting (makes the cells 'less sticky') prevents these events from happening. Aspirin also helps even if a heart attack or stroke does occur and often reduces the severity of the event.
"The benefits of aspirin go beyond the cardiovascular system. There is solid evidence that aspirin slows the progression of colon cancer, and some preliminary data suggests that regular aspirin use may prevent certain cancers from occurring at all," says Fendrick. "Also population-based studies report that an aspirin a day will either slow the progression or even prevent dementia, such as Alzheimer's disease," he continues.
"It appears that most people will get these benefits with very tiny doses -- only 81 milligrams a day or one baby aspirin," says Fendrick.
Since the risk of side effects goes up with the dose of aspirin, Fendrick recommends that most people who are using regular doses (325mg) switch to low-dose aspirin.
"Aspirin is not benign," says Fendrick. "Thousands of people die each year in the United States from complications related to taking aspirin and other NSAIDs.
"When you take aspirin, the level of stomach protection is decreased and you're more likely to bleed. Thus, people who take aspirin regularly -- even in a buffered or coated form -- will have roughly double the likelihood of having a perforated ulcer or bleeding in the GI tract," explains Fendrick.
"Relatively little attention is paid to this problem that kills more people in the U.S. each year than asthma or cervical cancer," he continues. The risk of stomach bleeding is increased substantially if aspirin is combined with other NSAIDs (both over-the-counter and prescription strength). These include the newer COX-2 selective NSAIDs, such as VIOXX and Celebrex that in the absence of aspirin are safer on the stomach.
"Ask your clinician if low-dose aspirin is right for you," says Fendrick. "While aspirin is potentially a life saver in many instances and we want to encourage its use, there are also many people taking this drug who don't realize that the risks of bleeding may greatly outweigh the health benefits gained."
Fendrick categorizes his patients into three groups. The 'must have' group is well-defined and is limited to individuals with a documented personal or family history of heart disease, such as coronary artery or vascular disease, or those with risk factors for heart disease such as diabetes, high blood pressure or high cholesterol.
The 'probably should take' group is more complicated, says Fendrick. "The benefits of aspirin for preventing colon cancer, dementia and heart attacks need to be carefully weighed by a medical professional against the potential for serious complications," he says.
Fendrick says individuals who shouldn't take aspirin on a daily basis include those with very low risk of developing the diseases aspirin is used to prevent. "For these people, such as your typical twenty-something reader of health magazines, the well-documented risks of aspirin overcome any health benefits that may be achieved," he says.
Facts about aspirin:
-Aspirin is acetylsalicylic acid and falls into a class called non-steroidal anti-inflammatory drugs or NSAIDs.
-Due to aspirin's blood thinning effect it can reduce coronary heart disease events and stroke.
-Research indicates that aspirin will slow the progression of cancer and may prevent it in the G-I tract.
-Research suggests that taking an aspirin a day will either slow the progression of, or even prevent, dementia.
-Aspirin has side effects including a reduction in stomach protection. When taking aspirin people double their likelihood of having a clinically meaningful bad event such as an ulcer.
Find more information on the World Wide Web at:
American Heart Association: Aspirin in heart attack and stroke prevention
http://www.americanheart.org
American Cancer Society: Baby aspirin may reduce risk of colon cancer
http://www.cancer.org
Alzheimer's Association: Fact Sheet: Anti-inflammatory Therapy
http://www.alz.org
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NEW FILM CAN PROTECT POULTRY FROM CAMPYLOBACTER INFECTION
To knock down the advance of the pathogen Campylobacter jejuni on raw chicken, Food Safety Consortium scientists Marlene Janes at the Louisiana State University Agricultural Center and Michael Johnson at the University of Arkansas have found that a coating of an invisible edible film on the chicken’s surface significantly reduces the level of contamination.
The edible film is most effective when it consists of a combination of three antimicrobial agents: two proteins – zein and nisin – and the compound EDTA, which does the lion’s share of the work in killing the pathogens. EDTA (ethylene diaamine tetraacetate) is a chelating agent, which means it binds to many different metal ions and prevents them from reacting with any other chemical that might be present. It is often used to clean people’s arteries of toxic metals in the bloodstream.
“Zein by itself, EDTA by itself and nisin by itself has some benefit,” explained Johnson, a food science professor at the UA Division of Agriculture. “But when the three compounds are combined you have your most effective treatment at refrigerator temperatures. It’s like putting multiple blockers out there in football to keep the bacteria from ever getting out.”
Janes’ and Johnson’s experiments showed that the EDTA treatment delivered the most killing power to the cocktail. Zein on its own doesn’t have much killing power, but adding zein to the mix provided the way to deliver the killing agent.
“It’s a food coating to give prolonged contact with the food surface,” Johnson said. “We’re using edible films to wrap chicken and provide a way for the delivery of
antimicrobial treatments.”
Raw poultry is susceptible to bacterial contamination during raw processing and this contamination can persist when such products are refrigerated at temperatures just above freezing, about 2 to 4 degrees C. Campylobacter jejuni, the leading cause of bacterial diarrhea, is a leading source of contamination in these circumstances.
Janes, who is now an assistant professor at LSU’s Ag Center food science department, said individual companies that want to use the cocktail’s ingredients already approved for use in other food products can receive approval to extend it to raw poultry by filing a petition with the U.S. Department of Agriculture Food Safety and Inspection Service.
“Companies are looking at this as a control measure,” Janes said. “They see that it’s something they can easily do.”
Much of the poultry market today consists of value-added chicken that only needs to be heated in the oven. Adequate cooking will kill pathogens. Raw poultry, however, is still a popular item in kitchens. If it comes out of the refrigerator with Campylobacter jejuni on the surface, heat will kill the pathogens in the oven, but there remains the danger of cross-contamination while the uncooked product is on the counter being prepared for the oven.
“We have to beware of people being careless in the kitchen with the raw chicken,” Johnson said. “They may fully cook the chicken, but did they disinfect their hands after handling the raw chicken and before making the salad or handling the rolls?” If the consumer didn’t take the precautions, raw poultry that has been treated with the invisible film and EDTA would be a safer bet to help avoid foodborne illness from this pathogen.
Previous research by Janes and Johnson has found ways to use similar antimicrobial wrappers of zein and nisin to protect ready-to-eat cooked poultry from Listeria monocytogenes, a deadly pathogen for which federal regulators have declared zero tolerance.
But Listeria isn’t a major threat on raw poultry as it is on ready-to-eat products. Johnson said. Listeria thrives best where it doesn’t have much competition from other bacteria and it likes cold places like the refrigerator.
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RHEUMATOID ARTHRITIS
Newswise — A promising new therapy for rheumatoid arthritis (RA) developed by researchers at the University of California, San Diego (UCSD) School of Medicine re-educates the body's immune system to prevent an attack against healthy joint tissue.
In patients with RA, the immune system that is supposed to protect the body, instead attacks it for unknown reasons. In a Phase I/IIa clinical trial recently described in Proceedings of the National Academy of Sciences*, the UCSD researchers report that a peptide called dnaJP1, taken orally for six months by a group of patients with early RA, caused no side effects and actually changed the action of the immune system's T cells, preventing them from attacking the body's own tissues.
The new therapy is currently in Phase II clinical trials with 160 RA patients at UCSD, Johns Hopkins University, the Mayo Clinic, and Virginia Mason Medical Center in Seattle. It is expected to be completed by the end of 2004, with enrollment still open for interested study participants.
RA is a chronic, painful disease that causes joint inflammation and destruction, progressive disability and premature death. Affecting an estimated 2.1 million Americans, RA causes substantial economic burden, with 50 percent of patients unable to work within 10 years of onset, and lifetime costs of the disease rivaling those of coronary artery disease or stroke. RA is incurable, with most therapy focused on symptom relief. Unfortunately, current therapies can have serious side effects and work by suppressing the immune system, which increases the risk of infection.
While the precise cause of the disease is unknown, researchers believe that RA is influenced by an abnormal reaction to environmental factors such as infection, which initiate the autoimmune response in genetically susceptible individuals.
The immune-modulation therapy developed by Salvatore Albani, M.D., Ph.D., UCSD professor of medicine and pediatrics, takes advantage of both the genetic and environmental components of RA. In studies over the past 12 years, he has focused on the immune system's T cells, which trigger inflammation to kill and clear foreign pathogens from the body. Albani reasoned that if the immune system of RA patients could be altered, T cells might be less likely to cause chronic inflammation.
His research involved several components of the immune response, beginning with a sequence of amino acids (segments that comprise proteins) expressed on the surface of cells during an immune response. Called a human leukocyte antigen (HLA), this sequence is designed to recognize self- from non-self cells. In a normal immune response, HLA acts as a "natural dimmer" to prevent over-stimulation of the inflammatory response. In RA patients, however, the dimmer is broken and excessive inflammation ravages tissue and joints. Interestingly, researchers have determined that 70 percent of RA patients, and not normal individuals, share a specific sequence of five amino acids within their HLA.
Albani's current findings were further supported by previous studies he conducted with Dennis Carson, M.D., UCSD professor of medicine and director of the Sam and Rose Stein Institute on Aging at UCSD, that showed immune-system T cells in RA patients become confused by the body's natural HLA sequence on cell surfaces, thinking it is a foreign invader. In an attempt to protect the body, the T cells attack the HLA sequence by inducing inflammation.
To prevent T cells from attacking the body's own HLA sequence, Albani sought to develop a vaccine therapy that could re-educate the diseased immune system in RA patients to prevent rampant inflammation. He focused on a naturally occurring protein called dnaJ that is used by T cells to help initiate the inflammation process. A section of the dnaJ protein, called dnaJP1, contains the same sequence of five amino acids as those within the HLA of RA patients. Bacterial, non-human forms of the dnaJP1 peptide also contained the same sequence of RA-susceptible HLA amino acids, and were found by the UCSD team to be targets of pro-inflammatory T cell responses in RA patients.
"Therefore, we believed that if we could administer the bacterial dnaJP1 as a vaccine to patients with early RA, it would affect the autoimmune inflammation," Albani said. "A key to the treatment was oral administration of dnaJP1."
The researchers determined that an injection of dnaJP1 caused a typical RA-inflammatory immune response, because T cells recognize the peptide as a foreign invader. When the peptide was ingested by patients, however, the special properties of the digestive system's mucosal cells recognized dnaJP1 as a "self-peptide," rather than foreign, and tolerated it. It's the same mechanism the digestive system uses with food, which is also a foreign invader to the body. The mucosal system is designed to tolerate the food, or medications, that enter the body in this manner.
"In essence, we re-educated the immune system T cells in RA patients to be tolerant of the dnaJP1 amino acid sequence that would usually trigger inflammation," Albani said. "In turn, the immune system became tolerant of the HLA sequence, thus avoiding a T cell attack against the body's own tissue."
He added that "the findings with dnaJP1 offer a strategy and the tools to develop a new therapy for RA that focuses on immune modulation rather than immune suppression."
Immune modulation may be particularly helpful in delaying, or possibly abolishing the need for RA patients to take currently available drugs called disease modifying antiarthritic drugs (DMARDs), which provide significant improvements in RA but have potentially serious side effects such as skin rash; mouth sores; stomach, eye and kidney problems; and low blood counts.
Links :
Trespassing foetal cells in mother's tissues might trigger autoimmune diseases like rheumatoid :
http://www.thenakedscientists.com/HTML/articles/article/dalyacolumn7.htm