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What's Hot
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| November 2001
Mechanism found for green tea in cancer fight In research conducted at H. Lee Moffitt Cancer Center & Research Institute in Tampa Florida, a mechanism of green tea polyphenols' ability to cause the death of cancer cells was elucidated. By testing green tea polyphenols effect on prostate cancer cell lines, varying concentrations of the polyphenols were found to diminish a protein called Bcl-XL which protects cancer cells from apoptosis, which is programmed cell death. Green tea has been shown to prevent several types of cancer in animal models. Human populations who consume green tea have lower rates of stomach, liver, pancreatic, breast, lung, esophageal and skin cancers. Aslamuzzaman Kazi, PhD, research fellow in the Drug Discovery Program at Moffitt Cancer Center, described the finding: "The higher the concentration, the better the response - meaning more apoptosis, or programming that tells cells to die -- apparently occurring as a result of a greater decrease in Bcl-XL, a protein that protects cancer cells from apoptosis. At all concentrations, response was apparent within three hours." Pin Dou, PhD, associate professor of oncology, biochemistry, and molecular biology at Moffitt further explained, "Because Bcl-XL is overexpressed in many cancers, it could be a key target in all these cancers and explain why green tea polyphenols (are) able to prevent human cancers in mouse models . . . Data from our laboratory suggests that at least one enzyme may modify Bcl-XL and that it is the actual target of tea. We also want to see if that target is present in all human cancers or just some of them." —D Dye
Chlorophylllin lowers aflatoxin-induced cancer risk In an early online release of the November 27, 2001 issue of the journal Proceedings of the National Academy of Sciences http://www.pnas.org, findings of researchers from Johns Hopkins Bloomberg School of Public Health demonstrated that chlorophyllin, a mixture of semisynthetic derivatives of chlorophyll found in plants, inhibits the liver cancer-causing damage induced by aflatoxin, a contaminant produced by molds in several plant foods. The researchers enrolled residents of Qidong, People's Republic of China, a population chronically exposed to aflatoxin and subsequently at risk for this form of cancer. In a double-blind study, one hundred eighty adults were randomized to receive 100 mg chlorophyllin or placebo three times per day for four months. Urine samples were collected at three months and examined for aflatoxin-N7-guanine adducts, a measure of genetic damage. The study participants who received the chlorophyllin supplements were found to have 55% less of these adducts than those who received the placebo. Study coauthor and professor of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health, Thomas Kensler, PhD, commented, "Our study shows that taking chlorophyllin three times a day reduced the amounts of aflatoxin-DNA damage by 55 percent, compared with taking a placebo. Taking chlorophyllin or eating green vegetables, like spinach, that are rich in chlorophyll may be a practical way of reducing the risk of liver cancer and other cancers caused by environmental triggers." John Groopman, PhD, professor and chairman of the Department of Environmental Health Sciences at the Bloomberg School of Public Health, and an additional author of the study, further explained, "Studies conducted by our coauthor, George Bailey of Oregon State University, have suggested that chlorophyllin acts as an 'interceptor molecule' to block the absorption of aflatoxins and carcinogens in the diet. Our study shows that chlorophyllin can effectively reduce aflatoxin levels, which should reduce the risk of liver cancer." —D Dye
More evidence that NSAIDs may help prevent Alzheimer's The November 22 2001 issue of the New England Journal of Medicine revealed the results of a study confirming the association between the use of nonsteroidal anti-inflammatory drugs, or NSAIDs, and a decreased incidence of Alzheimer's disease. Although previous studies had found an association, researchers considered the evidence inconclusive, and noted that the information in these studies was obtained retrospectively from patients, relatives or medical records. The latest prospective population-based study enrolled 6,989 individuals aged fifty-five and older who did not have dementia. The dispensation of nonsteroidal anti-inflammatories was tracked by pharmacies for most participants. NSAID use was classified by the researchers as short term, defined as one month or less; intermediate, lasting from one to twenty-four months, or longterm, classified as twenty-four months or longer. Adjustments in analysis of the data were made for age, education, smoking status, gender, and the use of certain drugs. In the 6.8 year follow-up, Alzheimer's disease was diagnosed in 293 subjects. Additionally, 56 developed vascular dementia and 45 developed other dementias. While use of NSAIDs at any time was associated with a lower incidence of Alzheimer's disease compared to nonusers, longterm use was associated with a significantly lower risk that was 80% lower than that of nonusers. The effect of the drugs on Alzheimer's risk did not appear to be related to drug dosage. The drugs did not confer protection against other varieties of dementia. It is believed that the cyclooxygenase inhibitory action of NSAIDs is the property responsible for their protection against Alzheimer's disease, by preventing inflammation and the resulting cellular response to glutamate. However, research published in the November 8 2001 issue of Nature http://www.nature.com showed that three NSAID drugs including ibuprofen have a different mechanism of action in preventing the formation of amyloid-beta plaque associated with the disease. —D Dye
Older individuals may be protein deficient The June 2001 issue of the Journal of Gerontology: Medical Sciences, revealed that the recommended daily allowance, or RDA, of protein may be inadequate to prevent loss of muscle in older people. The current RDA for those aged nineteen and older is 0.8 grams per kilogram body weight As an example, a woman weighing 120 pounds would need 44 grams protein per day to meet the RDA for protein. Previous studies of nitrogen balance in older individuals have shown that this may not be enough. The study, conducted by researchers from the University of Arkansas for Medical Sciences and the VA Medical Center in Little Rock, Arkansas, enrolled ten healthy men and women ages 55 to 77, and provided them with diets containing the recommended daily allowance of protein along with adequate calories to maintain their weights for fourteen weeks. The researchers utilized an outpatient setting for eleven weeks and an inpatient setting for three weeks to measure urinary nitrogen excretion, whole-body protein metabolism, whole-body composition and mid-thigh muscle mass. Mean urinary nitrogen excretion decreased over the course of the study, and by the fourteenth week, mid-thigh muscle area measurements had decreased compared to measurements taken during the second week of the study. The researchers, led by Dr Wayne W Campbell of University of Arkansas for Medical Sciences' Department of Geriatrics, believe that these declines point to metabolic accommodation by the body, a survival response in which the body responds to a decreased nutritional intake with a loss of or compromise in function. This suggests that the recommended daily allowance for protein is too low for this age group. The loss of appetite that occurs with aging may exacerbate this situation. —D Dye
Heart pump extends life of terminally ill In what has been called a landmark study published in the November 15 2001 New England Journal of Medicine, researchers supervised by Columbia Unversity's International Center for Health Outcomes and Innovation Research have discovered that implantation of a heart pump in terminal heart failure patients more than doubled their chances of living an extra year. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial enrolled 129 patients at twenty-two medical centers. The patients enrolled were were considered to be too old or to be in too poor health to receive heart transplants. Sixty-eight patients had the pump implanted and sixty-one received medical supervised drug therapy. Patients who received the implanted heart pump were found to be 52.1% likelier to survive for one year compared to 24.7% of terminal heart failure patients who were treated with drugs. Two year survival for the patients receiving the pump was 22.9%, whereas only 8.1% of controls survived this long. Recipients also reported improved quality of life, less depression and greater mobility than those on drug therapy. Thoratec Corporation is the manufacturer of the pump, a left ventricular assist device known as the Heartmate VE, which assists heart function weakened by congestive heart failure. The Heartmate VE ensures the circulation of blood from the left ventricle of the heart to the aorta, which is the main artery that exits the heart to deliver oxygenated blood to the rest of the body. Up to 100,000 people who are terminally ill with end-stage heart failure that are not transplant candidates could benefit from receiving the pump. Principle investigator Eric Rose, MD, chairman of surgery at Columbia Presbyterian Medical Center of NewYork-Presbyterian Hospital summarized, "This trial transforms decades of hopeful research into the development of man-made machines to support the failing heart into a successful long-term treatment." —D Dye
Aspirin as effective as standard blood thinner in prevention of stroke The November 15, 2001, issue of the New England Journal of Medicine published a study sponsored by the National Institute of Neurological Disorders and Stroke that demonstrated the ability of aspirin to prevent a second stroke as effectively as the anticoagulant drug warfarin. Antiplatelet therapies such as aspirin have been recommended following stroke in an attempt to prevent recurrence, nevertheless, second strokes still frequently occur. This trial sought to determine if warfarin possessed a superior ability to that of aspirin in prevention of second stroke occurrence, of which the risk in stroke patients is substantial. Warfarin inhibits circulating clotting proteins and aspirin affects blood platelets, both aiding in the prevention of blood clots that cause the most common type of stroke. The double-blind Warfarin versus Aspirin Recurrent Stroke Study is the largest trial yet comparing aspirin to warfarin in the prevention of second strokes. Over a seven year period, the trial enrolled 2206 patients who had previously been diagnosed with strokes caused by small vessel lacunar infarcts, large artery atherosclerosis and cryptogenic stroke of undetermined cause. Patients with atrial fibrillation or those with severe bleeding were excluded. Participants were randomized to receive warfarin or 325 mg aspirin and each were followed for two years. The two groups were matched for age, gender, severity of stroke, education, and risk factors consisting of hypertension, diabetes, cardiac disease, smoking, alcohol consumption, and physical activity. The subset of patients with a history of cryptogenic stroke appeared to be slightly benefitted more by warfarin, while in the other two groups aspirin was appeared somewhat effective at preventing strokes, however, an overall comparison of the therapies showed no significant difference between the two. The researchers believe that the increased efficacy of warfarin in patients with cryptogenic stroke could be due to the fact that these patients tend to form blood clots within the heart. The study also failed to show any increase in hemorrhage risk with aspirin or warfarin. Prior to this study, it was believed by some medical authorities that warfarin could be more effective in preventing blood clots than aspirin, although it has a greater potential for side effects. The outcome of this study reassures those using aspirin to prevent stroke recurrence that their therapy is as effective as warfarin, as well as safer and less expensive. Lead investigator, J. P. Mohr, M.D., director of the Stroke Unit at New York's Columbia University, summarized, "Treatment is far superior to no treatment and treatment with either aspirin or warfarin is safe under carefully monitored conditions." —D Dye
Hemochromatosis mutation associated with shorter lifespan In a study appearing in the November 12 2001 issue of the journal Archives of Internal Medicine, researchers studying the genetics of 1,784 individuals found that mutations of the HFE gene that are associated with hereditary hemochromatosis are found less frequently as a population ages, confirming an association with a shorter lifespan. Hereditary hemochromatosis is a genetic disorder of iron metabolism, affecting only one out of every 200 to 300 people, yet one in eight to ten individuals are carriers. The disease occurs most often in males, and is characterized by iron overload and the deposition of iron-containing pigments in the tissues. It is considered 100% fatal if not diagnosed and treated early. The research was carried out in Denmark, a country that has a large population of carriers of the mutation. The investigators examined the genetics of the 183 participants aged 100 or more in the Danish Centenarian Study, 601 individuals aged 92 to 93 who took part in the Danish 1905 Cohort, 400 participants aged 70 to 94 who participated in the Longitudinal Study of Aging Danish Twins, and 600 individuals who took part in a study of middle aged Danish twins whose ages ranged from 45 to 67 years. The researchers looked for a mutation most often associated with hereditary hemochromoatosis in exon 4 of the HFE gene, and discovered a trend toward fewer heterozygous carriers of the mutation with rising age. The trend was significant for the whole population and for women, but when men were analysed separately, the trend was not considered significant. As the carriers of the hemochromatosis-associated mutation were found less frequently in the older individuals of the groups studied, this indicates that carriers could face the risk of a shorter life expectancy. —D Dye
Blood substitute procedure could save lives In a study published in the November 2001 issue of Critical Care Medicine, researchers at University of North Carolina Chapel Hill described a new way to deliver an oxygen-carrying fluid into the aorta, the artery that emerges from the heart to deliver oxygenated blood to the body. The procedure, called selective aortic arch perfusion, can be used to rescue victims of trauma who experience significant blood loss and subsequent cardiac arrest. Research team leader and associate professor of emergency medicine at UNC-CH School of Medicine, James E Manning MD, explained, "This procedure involves taking a specialized balloon catheter developed here at UNC and advancing it though the femoral artery and into to the chest, into the aorta. When the balloon is inflated and the oxygenated fluid pumped in, the upper part of the body is selected for perfusion. It's about the fastest way to relatively isolate the heart and the brain and perfuse it with an oxygenating solution . . . Cardiac arrest due to blood loss, hemorrhage, especially after blunt trauma, has an almost 100 percent mortality. When there's cardiac arrest from severe injury, many surgeons consider resuscitation futile. If you can keep somebody like this alive, you may be able to get them to an operating room, stop the bleeding and repair the damage." The fluid used in the procedure is HBOC-201, a liquid hemoglobin-based oxygen carrier. In this study, pigs received experimental injuries involving significant blood loss and cardiac arrest. Six of the animals were treated with selective aortic arch perfusion with the liquid oxygen carrier and six were given the new procedure with saline. A return of heartbeat occurred only in the animals who received the HBOC-201. Dr Manning commented, "If we refine and improve this technique and show it is robust in further studies, it could prove very beneficial in human cardiac arrest." —D Dye
Another role for niacin in combating atherosclerosis The B vitamin niacin is a low cost therapy that has been used for decades to help lower serum cholesterol and triglycerides. A study published in the November 2001 issue of the journal Arteriosclerosis, Thrombosis, and Vascular Biology has established another mechanism of action for niacin, that of raising apolipoprotein A-I particles in high density lipoprotein, or HDL, the "good" cholesterol. There is evidence that HDL which contains only A-I has a greater antiatherogenic benefit than that which contains apolipoprotein A-I and and A-II. One hundred thirty-nine patients with HDL levels lower than 40 milligrams per deciliter, which are considered low, were randomized to receive one to two grams per day of extended release niacin or 1.2 grams gemfibrozil for nineteen weeks. Gemfibrozil is a drug that lowers cholesterol and triglycerides and and increases HDL cholesterol. A recent trial showed that the drug was able to increase HDL, resulting in a significant reduction in cardiovascular event risk, even though it did not effect LDL levels. In the current study, niacin was found to be more effective in raising HDL levels levels than gemfibrozil. The two gram dose of niacin increased apoliprotein A-I by approximately 24% and the one gram dose by 8.7%, whle gemfibrozil had no effect on apoliprotein A-I levels. In vitro studies of human hepatoblastoma studies by the researchers led to the speculatation that niacin's ability to decrease the enzyme lipase in the liver may play a role in its ability to reduce the removal of apolipoprotein-AI particles by this organ, leading to higher serum concentrations. In these studies, gemfibrozil failed to inhibit apolipoprotein-AI uptake by liver cells. As apoplipoprotein A-I particles are more efficient in removing cholesterol, elevation of apoliprotein A-I by consuming niacin is another way to help diminish atherosclerosis and cardiovascular disease. —D Dye
Study shows drugs responsible for almost one-fifth of hospital deaths A study published in the October 22 2001 issue of the journal, Archives of Internal Medicine has found that in a group of 13,992 patients admitted to a hospital in Norway, of the 732 deaths that occurred during a two year period, 18.2% were directly or indrectly determined to be caused by one or more drugs. In nearly half of these cases, an incorrect drug, form of the drug or dose was prescribed. The drugs most responsible for the deaths in this study were cardiovascular drugs, blood thinners and drugs that stimulated the sympathetic nervous system. Researchers examined the clinical records, autopsy reports and pre- and postmortem drug analyses of patients admitted to the Internal Medicine Department at the Central Hospital of Akershus, Norway. Of the 133 deaths resulting from adverse drug events, 75 were determined by autopsy findings and/or drug analysis data. This data was also used to rule out adverse drug events in the remaining deaths studied. The researchers found that fatal adverse drug events were more common when a higher number of drugs were taken, and in those who were older and had multiple diagnoses, than in those whose deaths were attributed to other causes. They also found that drug related deaths were more common in men and in patients with gastrointestinal diseases. Because many of these conclusions were based on postmortem findings, little of the information on drug related deaths made it into the patient's medical chart. Fatal adverse drug events appear to be a major, unrecognized problem in the elderly. The study's authors note that better interpretation of patient's symptoms and improved monitoring of drug concentrations could prevent some of these deaths. —D Dye
Vitamin D supplements reduce the risk of diabetes type 1 In a large study reported in the November 1 2001 issue of the journal, the Lancet it was found that infants who received 2000 international units per day of a vitamin D supplement experienced a reduced risk of the development of diabetes type 1 compared to children who received lesser amounts or none. It had previously been established that the vitamin reduces the risk of the disease in animals. —D Dye
Synthetic antioxidants extend lifespan and prevent decline in neurologic function In research conducted last year it was shown that synthetic catalytic antioxidants were able to extend lifespan in worms. A study published in the November 1 2001 issue of the Journal of Neuroscience extended these findings to mice and showed that they were able to correct neurological degeneraton. —D Dye
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