Large trial shows magnesium sulphate successful against pre-eclampsia
A trial conducted in thirty-three countries that included 10,110 women demonstrated that administration of magnesium sulphate to women with pre-eclampsia more than halved the risk of eclampsia and appeared to reduce the risk of maternal death. Pre-eclampsia is a disorder characterized by hypertension and protein in the urine that occurs late in pregnancy and which can lead to eclampsia: convulsions or coma. The condition occurs in 2-8% of pregnancies, and takes the lives of over 50,000 mothers every year. It also poses a risk to the child.
The report, published in the June 1, 2002 issue of The Lancet http://www.thelancet.com , examined magnesium sulphate's ability to prevent convulsions in pre-eclampsic women as compared to a placebo. Anticonvulsant drugs such as benzodiapines have been the previous therapy of choice, but there is little evidence that they improve the outcome of the condition. Magnesium sulphate, also used to correct a magnesium deficiency, was introduced as a therapy for pre-eclampsia almost a century ago, but has not gained worldwide acceptance due to little supporting evidence in the form of clinical trials and the lack of a theory to explain its mechanism of action.
The trial was the largest ever conducted for the hypertensive disorders of pregnancy. Four thousand nine hundred ninety nine women received with pre-eclampsia received magnesium sulphate, while the 4,993 received a placebo. Those receiving magnesium experienced a 58% lower risk of eclampsia than the placebo group. The magnesium group also experienced a lower rate of maternal mortality, although infant mortality was not affected.
An accompanying commentary in The Lancet stated that it was now up to those responsible for maternal health services to ensure that this effective, safe and inexpensive therapy is available to women everywhere.
- D. Dye
Broccoli compound kills H pylori
Sulforaphane, a compound found in broccoli that is believed to be responsible for many of the vegetable's health benefits, has been found by researchers at Johns Hopkins School of Medicine to help kill helicobacter pylori, or H pylori, the bacterium responsible for stomach ulcers and most stomach cancers. The researchers discovered that the compound can even kill H pylori that has become antibiotic-resistant.
The report, published in the May 28 2002 issue of the Proceedings of the National Academy of Sciences ( http://www.pnas.org/ ) presented the results of in vitro experimentation that demonstrated the ability of sulforaphane to kill H pylori both inside or outside of the cell. Cells lining the stomach act as reservoirs for the bacteria, rendering it more challenging to eliminate. Sulforaphane also helps prevent cancer by boosting the production of phase 2 enzymes within cells, which detoxify carcinogens and free radicals. When a carcinogen was administered to mice, sulforaphane blocked the formation of stomach tumors. Mice lacking the gene regulating phase 2 enzymes were not protected by the compound.
Research team leader and plant physiologist in the Department of Pharmacology and Molecular Sciences at the Johns Hopkins School of Medicine, Jed Fahey, stated, "In some parts of Central and South America, Africa and Asia, as much as 80 percent to 90 percent of the population is infected with helicobacter, likely linked to poverty and conditions of poor sanitation. If future clinical studies show that a food can relieve or prevent diseases associated with this bacterium in people, it could have significant public health implications in the United States and around the world . . . We've known for some time that sulforaphane had modest antibiotic activity. However, its potency against helicobacter, even those strains resistant to conventional antibiotics, was a pleasant surprise."
These latest findings may lead to trials in humans to determine if sulforaphane-containing vegetables can help combat H pylori infection.
More evidence for oxidative stress model of aging
The June 2002 issue of the journal Genetics will be publishing a report that adds even more credence to the theory that oxidation, or free radical damage, is a major cause of aging. Free radicals are damaging molecules produced during metabolism that can damage DNA, proteins, and other molecules. Antioxidants, such as vitamins C and E, neutralize these destructive molecules.
Researchers at the University of Southern California and the University of California at Irvine bred fruit flies with an extra copy of a gene whose product is the endogenous antioxidant superoxide dismutase, known as SOD. The gene was activated at maturity in one group of flies, while it remained switched off in a control group. The flies were genetically identical in every other aspect.
While the flies in whom the extra gene was not expressed lived a normal lifespan, the flies with the active SOD gene lived up to 40% longer. The researchers demonstrated that the flies producing more SOD used as much oxygen during their lifetimes as the control group, ruling out lowered metabolism as a mechanism of action. The magnitude of lifespan extension proved to be precisely proportional to the amount of additional superoxide dismutase production.
Associate professor of biological sciences John Tower, of the University of Southern California College of Letters, Arts and Science' molecular and computational biology program, commented, "It demonstrates that antioxidant activity is a rate-limiting factor for fly lifespan. There was no negative effect on metabolism from the SOD over-expression. So we're extending lifespan without some kind of trade-off or deficit in the creatures' metabolism."
Dr Tower speculated that pharmaceutical agents or gene therapy may some day be developed that would stimulate human cells to overexpress the gene for superoxide dismutase or similar genes.
Progesterone to be tried in brain injuries
The world's first trial of progesterone in the treatment of brain injury will soon be underway. The National Institutes of Health-funded study, called the ProTect (Progesterone for Traumatic brain injury, Experimental Clinical Treatment) trial, will be enrolling up to 100 patients with moderate to severe traumatic brain injuries over the next two years. The research will be conducted by scientists from Emory University and Morehouse School of Medicine, and will be based at Grady Memorial Hospital in Atlanta. Participants, who must be enrolled within ten hours of injury, will receive an intravenous infusion of progesterone or a placebo for three days following their injury. Evaluation of the subjects' mental status will be conducted at discharge from the hospital and one month later.
Progesterone is a hormone produced by both men and women that has been shown in rats to minimize swelling of the brain and speed recovery following traumatic brain injury. The hormone appears to prevent some of the inflammation that occurs after injury as well as block the formation of free radicals that can lead to the death of neurons.
Lead investigator and chairman of emergency medicine at Emory, Arthur Kellermann, MD, MPH, stated, ""Progesterone has been safely used for decades to treat medical conditions in both women and men, sometimes for months or even years at a time. Furthermore, progesterone has been safely given intravenously to humans at much higher doses than that planned in our study, which will limit progesterone treatment to only three days. In contrast to the many options available to treat other types of injuries, brain injury remains the final frontier. We want to take the crucial next step and determine whether giving progesterone to victims of moderate to severe traumatic brain injury will save lives and preserve mental function."
Antioxidants low in Alzheimer's disease patients
With the goal of producing further evidence of the role free radicals play in Alzheimer's disease by studying in vivo markers, the May, 2002 issue of Archives of Neurology published the results of a study that measured levels of oxidative damage and plasma antioxidants of forty Alzheimer's disease patients and 39 age and sex matched individuals without the disease. Blood samples were taken from both groups and white blood cell DNA levels of 8-OHdG (8-hydroxy-2'-deoxyguanosine), a marker of oxidative damage, were determined, as well as plasma levels of vitamins A, C, E and the following carotenoids: alpha-carotene, beta-carotene, lycopene, lutein and beta-cryptoxanthin.
Patients with Alzheimer's disease had significantly higher levels of 8-OHdG than the non-Alzheimer's group, indicating increased oxidative stress. All of the antioxidants tested were found to be lower in the Alzheimer's patient group, although the difference in lutein levels was not determined to be significant. A strong inverse relationship was observed between 8-OHdG and the carotenoids, with the exception of beta-cryptoxanthin. These findings indicate that the oxidative stress observed in Alzheimer's disease is related to poor antioxidant status.
Because the patients did not differ from controls in their dietary scores, malnourishment was questioned as an explanation for the low antioxidant levels found in Alzheimer's patients. Due to increased oxidation caused by the disease itself which is attributable to beta-amyloid and decreased cytochrome c oxidase activity, antioxidants may be consumed at a higher rate. The authors remark that therapeutic use of antioxidants has been proposed to slow the course of the disease, and note a study in rats in which supplementation with vitamin E was positively correlated with elevated levels in the animals' brains, providing evidence that raising plasma levels of antioxidants may positively effect brain levels.
CLA inhibits prostate and colorectal cancer cell growth
In research published in the March 28, 2002 issue of the journal Cancer Letters, scientists from Harvard Medical School reported that commercially available conjugated linoleic acid, or CLA, and its constituent isomers c9,t11-CLA, c9,c11-CLA, and t10,c12-CLA inhibited the growth of cancer in one human prostate and two human colorectal cancer cell lines. The t10,c12 isomer proved to showed the greatest effectiveness against colorectal cancer while both t10,c12-CLA and c9,t11-CLA were moderately effective at inhibiting prostate cancer. The t10,c12 isomer was found to cause caspase-dependent apoptosis in the prostate cancer cells and in one of the colorectal cancer cell lines.
CLA is part of the omega-6 fatty acid family, but its mechanism of action is similar to that of omega-3 fatty acids.
Assistant Professor of Surgery at Beth Israel Deaconess Medical Center and Harvard Medical School, and coauthor of the study, Dr John Palombo, commented, "There are specific isomers within CLA that exhibit an inhibitory effect on cancer proliferation . . . These in vitro results indicate that the cancer-reducing properties of CLA or its constituent isomers are not equivalent. The net reduction in cancer cell proliferation appears to be dependent upon the type and concentration of CLA isomer used. A better understanding of novel CLA preparations and their constituent isomers is required before initiating intervention (human clinical) trials of CLA in patients undergoing treatment of colorectal and prostate cancer, as well as individuals at risk for these cancers."
The researchers state that CLA preparations may prove effective as chemopreventive supplements for patients diagnosed with prostate or colorectal cancer, or for those at risk of the disease. An additional boon is the absence of adverse effects that often occur with pharmaceutical agents.
Pet owners: calorie restriction works for dogs too
In research that is the first of its kind to study dogs, it was found that calorie restriction can add extend the lifespan of these animals by fifteen percent compared to dogs allowed to eat as much as they want. This added nearly two years to the median lifespan of 11.2 years of the Labrador retrievers utilized in the study. Study coauthor Dr Dennis Lawler enthused, "We all know that obesity, whether human or canine, is bad for health -- that's not new news. What's exciting about this study is that, for the first time in a larger mammal, we proved that eating less resulted in longer life. That's powerful stuff."
In the study, published in the May 1, 2002 issue of the Journal of the American Veterinary Medical Association, researchers paired forty-eight week old dogs from seven litters with weight and gender-matched controls from the same litter. Control animals were allowed to consume as much food as they wanted during a daily feeding period, while animals in the restricted group received 25% fewer calories. Both groups were fed balanced diets that provided all of their nutritional requirements. At ten years of age, three dogs receiving the restricted diet had died compared to seven in the control group. At age thirteen and a half, twenty-five percent of the restricted dogs were still alive while none of the control group were. In addition to having less body fat and delayed lean body mass loss, the dogs in the restricted group showed the development of impaired gait and reduced activity at later ages than the control animals.
University of Wisconsin professor of medicine Richard Weindruch, MD, who is an expert in the field of dietary restriction, commented, "This study is significant for human as well as canine health because it's the first study completed in a larger mammal that proves the significant power that diet restriction wields in extending life and delaying the markers of aging. From this study, we can extrapolate that large mammals, including humans, can potentially live longer and healthier through diet restriction."
Life expectancy ceilings smashed
An article in the May 10 2002 issue of Science challenges the belief that human life expectancy is approaching its limit. By studying mortality patterns from several countries, Jim Oeppen of Cambridge University and J. W. Vaupel of the Max Planck Institute for Demographic Research in Rostock Germany have observed a precise linear trend in life expectancy that shows no signs of stopping.
In the past two centuries world life expectancy has more than doubled. Average life expectancy worldwide for women is currently 70 years while men can expect to live to age 65, contrasted to a life expectancy of approximately 25 years two centuries ago. Life expectancy in the United States exceeds the world average, and people in Japan can currently can expect to live the longest.
The authors make note of life expectancy predictions from 1928 to 1990 that have been exceeded by five years on average after their announcement. In 1990 S J Olshansky asserted that an individual age 50 should not have a life expectancy exceeding 35 more years unless major breakthroughs occurred in the field of aging. Women in Japan exceeded this limit in 1996.
The article presents graphs of life expectancy that provide remarkable visual confirmation of the steady incline in life expectancy since 1940 seen in Australia, Iceland, Japan, the Netherlands, non-Maori New Zealand, Norway, Sweden and Switzerland. The closely paralleling lines rise at a 45 degree angle to cut across 15 different estimates of life expectancy, including those calculated by the World Bank and the United Nations. The authors conclude that if life expectancy were close to a maximum that the increase in the record expectation of life would be slowing, which is not. They write, "For 160 years, best-performance life expectancy has steadily increased by a quarter of a year per year, an extraordinary constancy of human achievement."
More folate equals lower stroke risk
The May 2002 issue of the journal Stroke published the results of a population based study of men and women conducted over a nineteen year period which showed that those who had consumed the highest amounts of dietary folate experienced at 20% lower risk of stroke and a 13% lower risk of cardiovascular disease events. Although other studies have reported the same association, this study is the first the confirm it in a large representative sample of the U.S. population, rendering the findings widely generalizable.
The study analyzed data obtained from National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study participants who were between the ages of twenty-five and seventy-four and who did not have cardiovascular disease upon enrollment. Participants received medical examinations, laboratory tests and dietary assessments at the study's onset. Dietary intake of folic acid, saturated fat and calories were calculated. During the nineteen year follow up period, 3,758 cardiovascular events and 926 stroke events occurred among the 9,764 subjects.
Analysis of folate intake showed a reverse association between consumption of the vitamin and risk of stroke and cardiovascular events. This risk was consistent for men and women and in individuals with different levels of physical activity as well as in both smokers and nonsmokers. Participants in the group with the highest folate intake (greater than 300 micrograms per day) were more likely to have lower blood pressure and cholesterol than those who consumed less of the vitamin.
Folate may exert its benefits by lowering homocysteine, of which elevated levels increase the risk of cardiovascular disease and stroke. Supplementation with the vitamin has also been shown to reduce markers of endothelial dysfunction as well as the progression of atherosclerosis.
Drug companies top Fortune 500 list
While overall profits of Fortune 500 companies declined by over one half during the 2001 recession year, the top ten U.S. pharmaceutical companies increased profits by one third, to 37 billion dollars. According to a report released April 18 2002 by the national public interest organization, Public Citizen, average prescription drug prices increased by ten percent, contrasted with a 1.6 government inflation rate. The year 2001 saw an increase in 17% in spending on prescription drugs by U.S. citizens.
The top two drug companies were Merck and Pfizer who each own four drugs that have earned over one billion dollars in sales. Pfizer increased prices on their so-called blockbuster drugs by an average of 4.9 percent in 2001, while Merck's were increased by an average of 6.5 percent, quadruple the inflation rate. Twenty-nine other drugs reached blockbuster status in 2001 as well, doubling those who attained the distinction in 1999, and accounting for 34% of the total U.S. pharmaceutical market. These drugs had an average price of $97.71 which is almost double the national average. Heavy marketing is in part responsible for their success, although three companies were accused by the Food and Drug Administration of employing misleading advertising last year.
The pharmaceutical companies claim that this level of profits is necessary in order to successfully fund research and development, yet Public Citizen believes that research and development estimates may be overstated, and could be as much as 75% lower than the cost of $802 million dollars per new drug determined by one industry-funded study.
Frank Clemente, director of Public Citizen's Congress Watch, commented, "During a year in which there was much talk of sacrifice in the national interest, drug companies increased their astounding profits by hiking prescription prices, advertising some medicines more than Nike shoes, and successfully lobbying for lucrative monopoly patent extensions. Sometimes what's best for shareholders and CEOs isn't what's best for all Americans - particularly senior citizens who lack prescription drug insurance."
Twenty percent of new drugs later found to have serious adverse effects
The May 1 2002 issue of the Journal of the American Medical Association reported the results of a study that sought to determine the frequency of previously unrecognized adverse drug reactions occurring in recently approved drugs. By analyzing volumes of the Physician's Desk Reference published over a twenty-five year period as well as other information, researchers at Harvard University discovered that half of the newly established adverse effects, which include liver, bone marrow and heart damage as well as pregnancy risks, are found within seven years of their approval, and half of the drugs withdrawn were taken off the market within two years following their release. Study author and primary care physician and researcher at Cambridge Hospital and Harvard Medical School, Dr Karen Lasser, stated, "This study will change the way I talk to patients about the use of new drugs. If there is a safer, effective drug that has been in use for a number of years, I would strongly recommend it over a newer drug whose safety profile is unknown. I would prescribe a new drug only when absolutely necessary, and then watch for adverse effects very, very closely."
The authors attribute the widespread use of new drugs to extensive promotion by pharmaceutical companies. They note that drug companies may fail to conduct the postmarketing studies the Food and Drug Administration requires when a safety issue is discovered during the drug's preapproval phase.
Coauthor Dr. Paul Allen , an internal medicine specialist at Cambridge Hospital and Harvard Medical School, commented, "Twenty million patients, almost 10 percent of the U.S. population, were exposed to the five drugs withdrawn from the market between September 1997 and September 1998. Yet the drug companies push the public and doctors to use new drugs that are more profitable but also more dangerous."
Ancient remedy lowers cholesterol
In research funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases, scientists at the University of Texas Southwestern Medical Center in Dallas have discovered that an extract of guggul, an ayurvedic remedy used for millennia in traditional Indian medicine, can help to lower cholesterol. The study was published online Science Express Reports on May 2 2002.
The researchers found that guggulsterone, derived from the sap of Commiphora mukul, or guggul tree, blocked the farnesoid X receptor (FXR), which regulates the metabolism of cholesterol. Previous research at the University of Texas showed that this receptor is activated when bile acids reach a certain level, to interrupt the conversion of cholesterol to bile acids. Professor of pharmacology and University of Texas Howard Hughes Medical Institute investigator, Dr David Mangelsdorf explained, "The receptor keeps bile acids in check. If you disturb it, it changes how cholesterol is metabolized."
Acting on the discovery at Baylor College that guggulsterone blocked FXR in a gene assay, the scientists tested the compound in mice bred to lack FXR and mice in whom the receptor was intact. After feeding both groups a high cholesterol diet, they discovered that the compound lowered cholesterol in the animals who had the receptor but not in those without it, confirming that its mechanism of action is that of inhibition of FXR activation.
Dr Mangelsdorf predicts that this discovery will lead to the creation of new cholesterol-lowering drugs based on guggulsterone's structure that would help metabolize cholesterol in individuals with high levels. However, guggulsterone is widely available over the counter in gugulipid formulas.
Green tea may increase livers available for transplant
Research conducted at the University of North Carolina at Chapel Hill by Zhi Zhong PhD and colleagues has revealed that treatment with an extract of green tea prevented free radical damage from occurring in fatty livers after removal from the body. Fatty livers caused by alcohol abuse are frequently available for transplantation because the major source of transplant organs has been brain-dead victims of accidents that often involve alcohol. Liver graft failure and death has been more frequently associated with fatty grafts, rendering these livers unacceptable for transplants in most cases. The free radical formation that increases in fatty livers after transplantation appears to be the culprit in their failure.
In this study, reported at the American Physiological Society (APS) annual meeting in New Orleans, Louisiana, held April 20 - 24, 2002, researchers gave rats a dose of alcohol proportional to that which would produce inebriation from binge drinking in humans, followed by removal of the livers after twenty hours. The livers were implanted after being stored for twenty-four hours and rinsed with a solution containing green tea extract. Levels of free radicals, lipid peroxidation and enzyme release were measured. A control group of rats received healthy liver grafts.
The researchers found that rats who received fatty livers had four times the enzyme release of rats who received healthy livers and only 13% survived, compared to 88% of rats who received healthy grafts. However, fatty livers that were rinsed with a solution containing green tea prior to implantation had less graft injury and a 75% survival rate. While ethanol elicited a 2.5 increase in free radicals and increased lipid peroxidation, green tea extract prevented most of this from occurring. The free radical scavenging property of green tea polyphenols is believed to be responsible for its benefits, and could prove to be of value in increasing the amount of transplantable livers available.