What's Hot Archive
December 18, 2000
Ribavirin works by mutating hepatitis C virus
Ribavirin is one of the few drugs found to be effective for many hepatitis C patients. The Life Extension Foundation had recommended ribavirin for this difficult to treat disease years before it was approved in the United States for this purpose. In an article published in December's Nature Medicine, researchers at the University of California, San Francisco have discovered that ribavirin works by generating so many mutations to the virus that the virus is overwhelmed by them, which is known as error catastrophe. According to the researchers, this new discovery will help drug companies create more effective versions of ribavirin. It was previously believed that ribavirin worked by blocking an enzyme used when the virus copied its genome, but this was questioned because more potent inhibitors of the enzyme were not effective against the viruses treated by ribavirin. In this experiment, researchers added ribavirin to a virus in vitro and observed a correlation between the drug's antiviral ability and its mutagenic activity. At the highest ribavirin concentrations used in the study, only one of ten million virus particles were not killed by mutations.
Although RNA viruses such as the one that causes hepatitis C use their ability to mutate to help avoid treatments and vaccines, the excessive mutations generated by ribavirin help destroy the virus. "These viruses are incredibly clever. They use mutations to get around almost anything. But we now see that ribavirin adds so many extra mutations to the virus, that it is pushed into a kind of genetic meltdown," explained Shane Crotty, BS, of UCSF's Microbiology and Immunology Department. "This paper shows that mutagenesis is a valuable anti-viral drug strategy. And it's reasonable to assume that there are other drugs like this out there, but until now we haven't known the right way to look for them."
December 15, 2000
Prostate cancer slowed by immunotherapy
Researchers at the University of California, San Francisco have discovered that a new therapy that enables the immune system to kill prostate cancer cells can lower PSA and slow the progression of the disease. The study, published in the December issue of the Journal of Clinical Oncology, involved the collection of important immune system cells known as dendritic cells from the blood thirty-one men with hormone-refractory advanced prostate cancer. These cells scavenge foreign material and bring it to the attention of the lymphocytes, a type of white blood cell, which then destroy it. In this study, dendritic cells were combined with synthetic prostatic acid phosphatase, or PAP, an antigen that exists on the surface of most prostate cancer cells, and infused back into the patients once per month for three months in the hope it would train the patients' lymphocytes to recognize cells with PAPon them as a foreign substance.
Following the treatment, twenty of the participants, who ranged in age from 48 to 83 years of age, had a favorable immune response, with their time until disease progression at thirty-four weeks, compared to thirteen weeks for those who did not respond as well. Six patients also had a decrease in PSA, with half of these experiencing a decrease in PSA of 50%. PSA, or prostate specific antigen, is a protein in the blood that is a marker for prostate cancer.
Study author Eric Small, MD, Associate Professor of Medicine and member of UCSF's Comprehensive Cancer Center's Urologic Oncology program commented, "It really shows the immune system can be manipulated and made to recognize prostate cancer. This trial shows we can break tolerance to the antigen. Immunologically, we always thought we couldn't do that in prostate cancer. While other studies have shown immunotherapy to have some benefit in melanoma and kidney cancer, this study is one of the first to demonstrate an effect in prostate cancer"
December 13, 2000
Intravenous oxygen carrier lessens transfusion need
The 54th Postgraduate Assembly in Anesthesiology held in New York this week was the site of an announcement by Professor Donat R Spahn MD, of the Institute of Anesthesiology, University Hospital, Zurich Switzerland, that administration of Oxygent™ to patients who experienced blood loss during surgery caused either a complete avoidance of transfusion or the need for fewer units of blood than a control group. One of the functions of blood is the transportation of oxygen throughout the body. Oxygent, made by Alliance Pharmaceutical Corporation from a synthetic perfluorochemical compound, acts as an intravenous oxygen carrier when administered to people who have experienced blood loss. This is important in light of the existing nationwide blood shortage.
The international Phase 3 general surgery study enrolled 492 patients who underwent orthopedic, urologic, abdominal, vascular, and other major surgical procedures, many due to malignant disease, in which 424 lost anywhere from 10 to 80 milliliters blood per kilogram body weight. In the 424 patients who experienced this level of blood loss, those who received Oxygent either avoided the need for a blood transfusion or needed less blood. This statistic was observed throughout the study period following the patients' surgeries.
Duane J. Roth, chairman and CEO of Alliance commented, "Oxygent is the only oxygen carrier that is being evaluated in both cardiac and general surgery Phase 3 studies . . . We are excited about the potential for Oxygent to be an alternative to donor blood, which is in short supply in regions of the United States and Europe."
December 11, 2000
Proinsulin levels predictive of stroke
Proinsulin levels are frequently high in type 2 diabetics, and have been linked to the increased level of cardiovascular disease seen in this population, even more so than insulin. The pancreas of diabetics may increase proinsulin production in response to the increased insulin resistance experienced by diabetics. The December issue of Stroke: Journal of the American Heart Association reported a study of nondiabetics who had experienced a first stroke, in which proinsulin and insulin levels were measured. The incident case-referent study involved fifty-nine men and thirty-five women who had experienced their first stroke and one hundred seventy-eight controls matched for age and sex. Blood samples were collected before the strokes occured and insulin and proinsulin measured. The study adjusted for total cholesterol, systolic blood pressure, smoking, body mass index, and insulin.
The study found that high proinsuin levels elevated first-time stroke risk to more than triple that of those with lower proinsulin levels. The women studied experienced an even greater risk, with a synergistic risk factor of diastolic blood pressure noted.
The study indicates proinsulin levels as being a good predictor of first time stroke, particularly in women. The study authors note that increased exercise, improved diet and weight loss will lower proinsulin levels by decreasing insulin resistance. These lifestyle factors are important for anyone wishing to prevent all forms of cardiovascular disease.
December 8, 2000
New treatment for diabetic macular edema
Diabetes is the leading cause of blindness between the ages of twenty and seventy-four. Diabetic macular edema, or DME occurs when the retinal blood vessels of diabetic patients deteriorate, causing leakage. Of the nations 10.3 million diabetics, half a million have DME. Forty percent of all diabetics develop DME with 75,000 new cases diagnosed each year.
University of Kentucky College of Medicine Department of Opthalmology has helped develop a new treatment for DME that involves a simple surgical procedure which implants a device that provides sustained release of the drug fluocinolone acetonide into the back of the eye. Fluocinolone acetonide is an anti-inflammatory steroid that inhibits the growth of damaged blood vessels while it controls inflammation. The implant delivers consistent levels of the drug for up to three years. This limits whole-body exposure to the medication, reduces the necessary dose and the the need for frequent drug treatments.
Principle investigator P. Andrew Pearson, M.D., assistant professor, Department of Ophthalmology, UK College of Medicine commented, "This technology may offer the opportunity to treat DME with a drug instead of an invasive procedure. This may offer an effective method to improve the sight of patients afflicted with this terrible disease."
Five patients in a clinical study lead by Pearson received the implant in one eye while the other eye was left untreated. All patients experienced resolution of their macular edema in the eye that was treated and had improved visual acuity after nine months. The untreated eyes remained unchanged. Dr Pearson stated, "The results of this study are encouraging, especially because these patients had failed standard treatment, making their cases very difficult to treat."
The technology combined with other drugs is also is being studied to treat age-related macular degeneration, and uveitis, a severe intraocular inflammation, and is currently utilized in the treatment of CMV retinitis.
December 6, 2000
Liver Dialysis aids damaged liver
A liver dialysis machine that has been used by twenty-three hospitals so far in the United States was used for the first time in this country to support liver functions in a patient with trauma to the liver at University Medical Center, University of Arizona. The dialysis unit is being used on a gunshot wound victim with injury to over 70% of the liver. University Medical Center physicians decided to use the dialysis machine on the patient to help clear toxins from the bloodstream to relieve the liver of some of its stress and enable it to regenerate. Steven B. Johnson, M.D., associate professor of surgery in the Section of Trauma and chief of Surgical Critical Care at the University of Arizona College of Medicine, stated "The liver dialysis unit basically is taking over many of the functions of the liver so that the patient can heal . . . Having the technology to provide liver dialysis gives UMC an effective tool for the treatment of patients with liver disease, drug overdoses, and with severe injuries to the liver."
Liver dialysis is accomplished by the use of a compact, mobile and self-contained system. It's approximate size is that of a dishwasher and it can be wheeled into the patient's room. It works by removing toxins or external or internal origin from the blood to prevent further deterioration that can lead to multiorgan failure and ultimately death. Without coming into contact with the blood, powdered activated charcoal and other chemicals remove toxins. It is the only technology approved by the FDA to assist those suffering from liver decompensation or drug overdose. Treatment lasts from four to six hours over a period of two to five days.
As little was has been available to assist damaged livers, this new technology could prove to be a lifesaver.
December 4, 2000
Folic acid antagonist-caused birth defects reduced by vitamins
Commonly prescribed drugs that act as antagonists to the B vitamin folic acid are classified as either dihydrofolate reductase inhibitors, which includes the drugs aminopterin, methotrexate, sulfasalazine, trimethoprim, triamterene, pyrimethamine, or those that antagonize folic acid in a different manner, including antiepileptic drugs carbamazepine, phenytoin, phenobarbital, and primidone. Research has shown that folic acid deficiency is the cause of neural tube defect (spina bifida) as well as other defects such as cleft palate or cleft lip, cardiovascular defects such as patent ductus arteriosus, atrial septal defects, coarctations of the aorta, and pulmonary-valve anomalies, and several urinary tract defects. A study published in the November 30 New England Journal of Medicine sought to determine if the use of folic acid antagonists during pregnancy increased these defects in the children of the women taking them and if the use of folic acid during pregnancy might prevent some of these defects.
The mothers of 1,962 infants with oral clefts, 3,870 with cardiovascular defects, and 1,100 with urinary tract defects were interviewed by trained nurses within six months of their delivery about drugs taken during their pregnancies. The mothers of 8,387 children with defects not due to folic acid deficiency were also interviewed. It was found that those mothers who took the folic acid antagonists during the second or third month after their last menstrual period had a greater risk of having children with birth defects known to be caused by folic acid deficiency, and that this risk was modified if they were also taking multivitamins. The reduction in risk attributed to vitamin use was not observed, however, with those taking antiepileptic drugs in this category (carbamazepine, phenytoin, phenobarbital and primidone), and the authors suggest that these drugs may contribute to birth defects by a mechanism other than folic acid antagonism.
The research conclude by affirming the observation that the folic acid component of multivitamins may reduce neural-tube defects as well as the incidence of other malformations.
December 1, 2000
Creatine protects brain from injury
Creatine is a popular nutritional supplement among body builders and athletes, used to enhance endurance and muscle gain. Creatine is synthesized in the body from the amino acids arginine and glycine. It is absorbed by and stored in the major skeletal muscles and the heart. Creatine use maintains higher levels of ATP, or adenosine triphosphate, the cell's energy molecule. In research published in November's Annals of Neurology, creatine was shown to also have the ability to reduce the loss of neurons in the brain's cortex that occurs after injury. Researchers at the University of Kentucky gave creatine to mice for periods of one, three or five days before inflicting trauma that resembles human closed head injury (the closed cortical impact model). The mice who received the creatine three and five days before receiving the head injuries had 36% less damage one week later than the control mice. The researchers reported a similar experiment in which rats were given creatine four weeks prior to receiving head injuries had half the loss of neurons than the placebo group. Creatine evidently works by benefitting the mitochondria, which are the cell's energy producing power plants. The rats' brains were found to have increased mitochondrial membrane potential, and levels of calcium and damaging reactive oxygen were reduced within the mitochondria. Levels of ATP were maintained.
The researcher team, led by Dr Stephen W Scheff, commented, "This food supplement may provide clues to the mechanisms responsible for neuronal loss after traumatic brain injury and may find use as a neuroprotective agent against acute and delayed neurodegenerative processes."
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