LE Magazine November 2001
Studies from throughout the world that can help you live longer
November 2001 Table of Contents
1. Melatonin reduces kidney failure
A recent study evaluated the effect of melatonin, a potent free radical scavenger, on mercury-induced kidney failure. Rats received 1 mg/kg of melatonin or placebo, 30 min before the mercury (mercuric chloride). Melatonin pretreatment (melatonin blood levels of 3 mg/ml at the time of mercury administration) prevented the increment in blood creatinine and reduced death of kidney tubules from 41 to 4.2! In the group untreated with melatonin, apoptosis (cell death) and post necrotic proliferative activity (the sum of morphological changes indicative of cell death and caused by the progressive degradative action of enzymes) were twice more intense. Melatonin prevented an increase in kidney content of malondialdehyde (MDA, stress marker) and decrease in glutathione (GSH) resulting from mercury toxicity. Melatonin also induced an important reduction in superoxide-positive cells. Thus, the beneficial effects of pharmacological doses of melatonin in kidney disease are due to its antioxidant properties.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2000, Vol 279, Iss 5, pp F910-F918
2. Risk factors for gastric cancer
Gastric cancer is generally thought to arise through a series of gastric mucosal changes. To try to determine the cause, a study was conducted in 1989 to 1990 among 3,433 adults in China, in a region with very high rates of gastric cancer. Data on cigarette smoking, alcohol consumption and other characteristics of the participants were obtained by interview in 1989 to 1990. Antibodies to H. pylori (bacteria) levels of serum micronutrients, and other characteristics at the start, were compared between those whose condition showed progression to dysplasia or gastric cancer from the beginning of the study to 1994 and those with no change or with regression of their lesions over the same time frame. Results showed that the presence of H. pylori at the start was associated with an increased risk of progression to dysplasia or gastric cancer by 88%. The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% among those with starting vitamin C levels in the highest amount. Thus, H. pylori infection, cigarette smoking and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in a high-risk population.
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, Vol 92, Iss 19, pp 1607-1612
3. Melatonin protects against damage by ionizing radiation
Ionizing radiation is a potent carcinogen, and its injury to living cells is, to a large extent, due to free radical stress. DNA is the molecule most often damaged by ionizing radiation. Hydroxyl radicals (OH), considered the most damaging of oil free radicals generated in organisms, are often responsible for this. Melatonin is an antioxidant that protects DNA, lipids and proteins from free-radical damage. It works by stimulating the activities of antioxidant enzymes and scavenging free radicals directly or indirectly. Among known antioxidants, melatonin is a highly effective scavenger of (OH). Melatonin is distributed widely in organisms and in all cellular compartments, and it quickly passes through all biological membranes. The protective effects of melatonin against oxidative stress caused by ionizing radiation have been documented in studies in different species and in in vitro experiments that used human tissues. Melatonin has been given to humans and then tissues collected and subjected to ionizing radiation. The radioprotective effects of melatonin against cellular damage caused by free radicals and its low toxicity make melatonin a treatment or cotreatment when minimizing the effects of ionizing radiation.
PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE, 2000, Vol 225, Iss 1, pp 9-22
4. Free radicals decrease age-related aerobic efficiency
A study was designed to test the free radical theory of aging by using the fruit fly. Oxygen free radicals are generated by mitochondria (cell organelles that produce cellular energy) during the process of normal oxidative metabolism. Age-specific measurements of oxygen consumption, heat production and anti-oxidant enzyme activity were obtained from two lines of male flies, one selected for longevity and one normal-lived. The findings demonstrate that although oxygen consumption remains relatively constant over the majority of the life span of each line of flies, aerobic efficiency declines with advancing age. This loss of aerobic efficiency manifests itself as a decline in total body metabolism as measured by heat production, and appears to be associated with an age-specific increase in damage inflicted upon mitochondria by oxygen free radicals.
JOURNAL OF INSECT PHYSIOLOGY, 2000, Vol 46, Iss 11, pp 1477-1480
5. Coronary heart disease risk reduction
Regardless of the intervention used (diet, surgery, drugs), reduction of blood cholesterol has consistently produced a reduction in cardiovascular risk. In addition, low levels of high-density lipoprotein (HDL) and high levels of triglycerides (particularly in conjunction with an LDL/HDL ratio >5) are particularly strong risk factors for CHD. Studies of statins have shown conclusively that lowering LDL cholesterol levels reduces CHD and total mortality. Statins are the most potent lipid-lowering drugs available for lowering LDL cholesterol and have become the drug of choice for those with hyperlipidaemia who require drug therapy. A general approach to preventing cardiovascular disease should include strategies to reduce the overall CHD risk by lifestyle modification and management of modifiable risk factors such as smoking, hypertension and diabetes.
QJM-MONTHLY JOURNAL OF THE ASSOCIATION OF PHYSICIANS, 2000, Vol 93, Iss 9, pp 567-574
6. Advances in stem cell transplantation
Stem cell transplantation of male reproductive cells has been a technological breakthrough in the study of stem cells. Stem cells from the testis have been successfully transplanted from one animal to another of the same species (syngeneic transplants) and sometimes to an animal of a different species (xenogeneic transplants). This transfer technique, combined with developments in cryopreservation (maintaining tissue at very low temperatures), long-term culture, and the enrichment of stem cell populations makes more breakthroughs that are significant likely in the near future. Spermatogonial stem cell transfer will allow transplantation of cultured stem cells manipulated genetically in culture to give rise to functional male gametes (reproductive cells) with an altered genetic makeup. This achievement will have applications in basic science, human medicine, and domestic and wild animal reproduction. Potentially significant barriers remaining to be overcome are the stable incorporation of genetic material into stem cells, and immunological responses to the introduced germ cells. The full article reviews the scientific advances made since the initial report of successful transplantation in 1994.
REVIEWS OF REPRODUCTION, 2000, Vol 5, Iss 3, pp 183-188
7. Raloxifene for heart disease and breast cancer?
Raloxifene is a selective estrogen-receptor modulator (SERM) that has been-approved for use in the prevention and treatment of osteoporosis in postmenopausal women. A SERM interacts with estrogen receptors, functioning as an agonist in some tissues and an antagonist in others. Because of their unique pharmacologic properties, these drugs can achieve the desired effects of estrogen without the possible negative stimulatory effects on the breasts or uterus. Approximately 60% of a dose of raloxifene is rapidly absorbed from the gastrointestinal tract. However, bioavailability is only 2%. In postmenopausal women, raloxifene has an estrogen-like effect on bone turnover and increases bone mineral density (BMD). It reduced the risk of fractures in women with osteoporosis. Raloxifene also seemed to reduce the risk of breast cancer and positively influenced blood lipid markers of cardiovascular disease. The most common adverse effects are hot flashes and leg cramps. A serious possible adverse effect is venous thromboembolism (obstruction of a blood vessel). The recommended dosage is 60 mg/day. The future role of raloxifene will be determined by its cardiovascular or breast cancer benefits. It is an alternative to traditional hormone replacement therapy (HRT) for the prevention and treatment of osteoporosis in certain postmenopausal women.
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY, 2000, Vol 57, Iss 18, pp 1669-1675
8. Strategies to reduce the risk of virus-related cancers
Experimental evidence has established an association between at least eight viruses and various cancer sites. Recent estimates (at least 10% of cancers worldwide) have revealed that viruses, together with tobacco and diet, account for the largest proportion of cancer in the world. Improvements in the detection of viruses and biomarkers of chronic infection have led to the identification of strong associations with cancer, particularly for human papillomavirus (HPV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV). For some cancer viruses like HIV and hepatitis C virus (HCV), the spectrum of malignancies involved still needs to be well defined. For HBV and HPV, vaccination aimed at cancer prevention is already a reality or a possibility. Whereas HBV vaccination already emerged as one of the most cost-effective ways to reduce adult cancer mortality, for HPV vaccination some technical problems still await a solution. For other infectious agents such as HCV and HIV, prospects for a vaccine are not immediate. In order to apply new knowledge on viruses to cancer prevention, large vaccination trials (many thousands of people), and prolonged (5 to 10 years) are needed. These will have to match scientific excellence with a feasible design. Mistrust between scientists and the public will have to be prevented by means of absolute openness in scientific information and economical interests involved.
ANNALS OF ONCOLOGY, 2000, Vol 11, Iss 9, pp 1091-1096
9. Potent free radical scavenger in red grapes
Resveratrol is a natural product occurring in grapes and various other plants with medicinal properties. The phenolic antioxidant has been identified as a potential cancer chemopreventative, and its presence in red wine has been suggested to be linked to the low incidence of heart disease in some regions of France (the French Paradox). Recently, however, resveratrol was reported to promote DNA fragmentation in the presence of copperions. A study thus investigated this phenomenon in detail. By acting as a reducing agent, resveratrol was found to promote hydroxyl-radical (OH, a potent free radical) formation by DNA-bound copper ions. However, in the presence of either vitamin C or glutathione, the phenolic lost this property and behaved as an antioxidant. In the vitamin C system, resveratrol had no effect on the rate of OH formation, but actually protected DNA from damage by acting as a radical-scavenging antioxidant. In contrast, in the natural glutathione system, resveratrol inhibited OH formation by a mechanism involving the inhibition of glutathione disulfide formation. It was therefore concluded that the DNA-damaging properties of resveratrol, identified recently in one 1998 study, will be of no significance under physiological conditions (vitamin C and glutathione, etc.). To the contrary, this investigation has demonstrated that the phenolic behaves as a powerful antioxidant, both via classical, hydroxyl-radical scavenging and by a glutathione-sparing mechanism.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2000, Vol 381, Iss 2, pp 253-263
10. Telomerase targeted to fight cancer
Telomerase is an enzyme highly active in cancer cells, which affects the telomeres (ends of chromosomes) and helps to preserve chromosome structures during the corrosive process of cell replication. Scientists have been studying several approaches to treating cancer by disrupting telomerase activities. A new study may produce new therapy approaches to treating breast and prostate cancer. In the study, a small mutation was inserted into the enzyme's genetic coding, composed of ribonucleic acid (RNA). The mutated RNA prevented the normal activities of telomerase in translating RNA to DNA in order to rebuild portions of the chromosome, which was lost in cell replication. The growth of cancer cells then slowed to the point of cellular "suicide." Cancer cells are very good at resisting signals that tell them to commit suicide. This is one of the things that make them so dangerous. However, low levels of the mutant RNA dramatically decreased growth rates of breast and prostate cancer cells in the study and made more cells die. The mutation resulted in smaller breast cancer tumors in live mice implanted with the mutated enzyme. Telomerase mutation offers an advantage as an approach for treating cancer with immediate impact on tumor cells. Thus, the mutation used telomerase to destroy rapidly multiplying cancer cells.
Proceedings of the National Academy of Sciences, 2001 98: 7649-7651
11. Vitamins C and E prevent tissue damage
The rupture of the protective membrane surrounding the fetus has been associated with infection, cigarette smoking and bleeding. Hypochlorous acid (a free radical) is a necessary "evil" for the body to fight infection. Yet, while destroying pathogens, it may damage surrounding tissue. There was extensive damage to amniotic epithelium and collagen resulting from hypochlorous acid exposure, which was dose related. However, pretreatment provided by antioxidant therapy, vitamins C and E, prevented this damage in all cases.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2000, Vol 183, Iss 4, pp 979-985
12. Homocysteine levels in vegetarians vs. omnivores
Vitamin B12, folic acid and vitamin B6 are the main determinants of homocysteinemia (high level of homocysteine in bloodstream). The vegan diet provides no vitamin B12, but also less strict forms of alternative nutrition may suffer from a deficit of this vitamin. Blood homocysteine level was measured in alternative nutrition groups of adults (lacto- and lactoovovegetarians and vegans) and compared with the levels in a group consuming a traditional diet (omnivores). In the vegetarians, the average homocysteine level was 13 vs. 10 mu mol/l in omnivores. The frequency of hyperhomocysteinemia is 29% vs. 5% in omnivores. In the vegans, the average homocysteine value was 15 mu mol/l (53% of the individual values exceeded 15 mu mol/l). Omnivores consume the recommended amount of methionine. However, in those consuming an alternative diet, the intake of methionine is deficient because there is a lower content of methionine in plant proteins. The vitamin B12 levels are significantly lower in the alternative nutrition groups (214 pmol/l in vegetarians vs. 140 pmol/l in vegans vs. 344 pmol/l in omnivores). A deficit of B12 was found in 26% of the vegetarians and in 78% of the vegans vs. 0% in omnivores. Folic acid levels were significantly lower in omnivores. The results show that: 1) a consequence of vitamin B12 deficiency, being a result of alternative nutrition, is mild hyperhomocysteinemia, and 2) non-vegetarians had much lower levels of folic acid.
ANNALS OF NUTRITION AND METABOLISM, 2000, Vol 44, Iss 3, pp 135-138
13. Determinants of artery disease in the elderly
A study examined the atherosclerotic risk factors for peripheral arterial disease (PAD) in 6,450 men and women (aged 55 years +). The results showed that determinants strongly and independently associated with PAD were age of at least 75 years, fibrinogen level, cigarette smoking, diabetes and systolic blood pressure. An opposite relation of high-density lipoprotein (HDL) cholesterol level with PAD was found. Men and women did not show differences in risk factors for PAD. In total, 69% of the occurrence of PAD is attributable to cardiovascular risk factors measured in the study. Smoking accounted for most (18%). The results suggest that prevention of PAD should be directed at fibrinogen level, HDL cholesterol level, smoking, systolic blood pressure and diabetes.
ARCHIVES OF INTERNAL MEDICINE, 2000, Vol 160, Iss 19, pp 2934-2938
14. Low retinol levels and liver disease
Retinol, a vitamin A derivative, affects the differentiation (increase in structural heterogeneity) and growth of many tissues and has anti-tumor properties. A study investigated blood retinol levels as a risk factor for the development of liver cancer in 175 adults (34 with chronic hepatitis C, 117 with cirrhosis [inflammation] and 24 with cancer). Results showed that average blood retinol levels were 972 ng/mL in the control group and 647 in those with chronic hepatitis C. There was a more significant difference in blood retinol levels between those with Child-Pugh grade A cirrhosis and those with cirrhosis/cancer (532 vs. 366). There was a significant difference between normal controls and all patients' groups, and 60% of those with cirrhosis/cancer had blood retinol levels below 350 ng/mL, compared with only 18% of those with cirrhosis with no cancer. Thus, there was a progressive reduction in blood retinol levels from control groups to patient groups with liver cirrhosis. Those with cirrhosis and cancer had significantly lower values of retinol than those with cirrhosis alone. Therefore, blood retinol levels may be a risk factor for the development of liver cancer.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2000, Vol 14, Iss 10, pp 1295-1301
15. Gene therapy for prostate cancer: Where are we now?
Medical research has been revolutionized by gene therapy. Gene therapy recombines specifically and alters DNA sequences, and by techniques to transfer these sequences or even whole genes into normal and diseased cells. The full article reviews the relevant background information, outlines current treatment strategies and clinical trials, and discusses current challenges facing the field of gene therapy for advanced prostate cancer. It looks at PubMed and recent abstract proceedings from national meetings, relevant to gene therapy and advanced prostate cancer. It selected literature representative of the scientific background for current gene therapy strategies and National Institutes of Health Recombinant DNA Advisory Committee approved clinical trials. Current prostate cancer gene therapy strategies include: 1) correcting aberrant gene activity, 2) exploiting programmed cell death pathways, 3) targeting critical cell biological functions, 4) introducing toxic or cell lytic suicide genes, 5) enhancing the immune system antitumor response and 6) combining treatment with conventional cytotoxic chemotherapy or radiation therapy. The challenges that lie ahead for gene therapy include: 1) improving the efficiency of transferring DNA to nearby cells, and to distant sites, 2) enhancing the levels of gene activity, and overcoming the immune responses that limit the time that genes are activated. Despite these challenges it is certain that gene therapy will be part of the urological arsenal against prostate cancer in this century.
JOURNAL OF Urology, 2000, Vol 164, Iss 4, pp 1121-1136
16. Age-related decline in physical activity
The question of whether the age-related decline in physical activity has a biological basis in humans was addressed. The full article review provides strong support for a biological basis of this phenomenon. First, age-related decline in activity measured in many different ways is observed across a wide range of animals. Second, the activity decline appears predictive of life span. Increased levels of activity predict longevity, and increasing activity through exercise increases median life span. Third, activity declines appear related to altered neurotransmission involving the central dopamine system. Reduced dopamine release or loss of dopamine receptors appears to underlie age-related activity decline. Intervention that enhances dopamine function can increase activity levels in aged animals.
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 2000, Vol 32, Iss 9, pp 1623-1629
17. Anti-inflammatory effect on liver cells in viral hepatitis
A licorice root extract (Glycyrrhizin) has anti-inflammatory activity and has been used for the treatment of chronic viral hepatitis. Glycyrrhizin inhibited cytolytic activity of complement via the activation of different pathways. (Complement is a series of enzymatic proteins in normal blood that combine with antigen-antibody complex band which cause destruction of cells [lysis] and bacteria, and are involved in various immunological and biological activities). Glycyrrhizin inhibited the pathway in which the membrane attack complex (MAC) is formed. This mechanism suggests that glycyrrhizin may prevent tissue injury caused by MAC not only in chronic hepatitis but also in many autoimmune and inflammatory diseases.
MICROBIOLOGY AND IMMUNOLOGY, 2000, Vol 44, Iss 9, pp 799-804
18. Eat to live, not live to eat
Most of the prevailing chronic diseases in the world have an important nutritional component by directly causing a specific disease, enhancing the risk through a phenomena of promotion, exerting a beneficial effect in decreasing risk or preventing the disease. International studies have shown that a particular disease may have vastly different occurrence and mortality depending on where the person resides. It has been found that regular intake of foods with saturated fats such as meat and certain dairy products raise the risk of coronary heart disease. The total mixed-fat intake is associated with a higher incidence of the nutritionally linked cancers, specifically cancer of the postmenopausal breast, colon, prostate, pancreas, ovary and endometrium. The associated carcinogens, toxic to genes, for several of these cancers are heterocyclic amines, which also play a role in causing heart disease. These are produced during the broiling and frying of creatinine-containing foods such as meats. Monounsaturated oils such as olive or canola oil are low-risk fats since the incidence of specific diseases is lower in the Mediterranean region, where such oils are customarily used. High salt intake is associated with high blood pressure and with stomach cancer, especially with inadequate intake of potassium from fruits and vegetables and of calcium from certain vegetables and low-fat dairy products. Vegetables, fruits and soy products are rich in antioxidants that are essential to lower disease risk stemming from free radicals in the body. Green and black teas (polyphenols) are excellent sources of antioxidants, as is cocoa and some chocolates. Nutritional lifestyles that offer the possibility of a healthy longer life can be adopted by most populations in the world.
NUTRITION, 2000, Vol 16, Iss 9, pp 767-773
19. Vitamin B6 vs. seizures
A study followed up with 25 individuals with West syndrome (special type of epileptic seizure, first described by Dr. West in 19th century) that was responsive to vitamin B6 (8 cryptogenic and 17 symptomatic patients). All cryptogenic patients and seven symptomatic patients had intelligent quotient or developmental quotient scores of 75 or higher. All cryptogenic patients and 13 symptomatic patients were seizure free at the last follow-up (3 years). Vitamin B6 could successfully be discontinued in four cryptogenic and four symptomatic patients who were 20 months to 24 years old.
PEDIATRIC NEUROLOGY, 2000, Vol 23, Iss 3, pp 202-206
20. Garlic consumption and cancer prevention
The active ingredients in garlic have demonstrated an anticarcinogenic effect in animals and in culture. A study analyzed the literature (18 studies) on the association between garlic consumption (raw garlic, cooked garlic or both-RC garlic) and risk of stomach, colon, head and neck, lung, breast and prostate cancers. The consumption reference categories ranged from no consumption to consumption of >28.8 g/wk. The average difference between the highest and lowest categories was 16 g/wk. The risk estimate of colorectal cancer and RC garlic consumption, excluding garlic supplements, was 31%; for stomach cancer, a 47% lower risk. Thus, high intake of RC garlic may be associated with a protective effect against stomach and colorectal cancers.
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2000, Vol 72, Iss 4, pp 1047-1052
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