LE Magazine, September 2000 - Medical Updates

September 2000
Table Of Contents

1. Effects of SAMe on brain oxidative stress

   Full source: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2000, Vol 361, Iss 1, pp 47-52

   SAMe (S-adenosyl-L-methionine) used to treat liver diseases and as antidepressive medication, has neuroprotective effects in animals. A study looked at the long-term antioxidant effects of SAMe in brain tissue. Forty rodents were given 10 mg SAM/kg per day, and 40 others were given an equivalent volume of the amino acid, L-lysine (the commercial solvent for SAMe). Results showed that chronic treatment with SAMe decreased maximum forebrain production of thiobarbituric acid-reactive substances (TBARS) by 46% compared with animals given L-lysine. It increased glutathione levels by 50%, GSHpx enzyme activity by 115% and GSHtf enzyme activity by 81.4%, both related to glutathione metabolism. In culture, lipid peroxidation was inhibited (13.1 controls vs. 5.9 with 1000 mu mol/l SAMe) and glutathione levels were stimulated (0.97 in controls vs. 1.55 with 1000 mu mol/l SAMe), as were GSHpx and GSHtf. No significant effect was seen in any of the experiments with L-lysine. Thus, SAMe has antioxidant effects in rat brain tissue both in the body and in culture seen both as inhibition of lipid peroxide production and as an enhancement of the endogenous glutathione antioxidant system.

   
   
   

2. Effects of lowered melatonin secretion in middle age

   Full source: ENDOCRINOLOGY, 2000, Vol 141, Iss 2, pp 487-497
   
   Pineal melatonin secretion declines with aging, whereas visceral fat, insulin, and leptin in the blood tend to increase. Previous studies have demonstrated that daily melatonin administration at middle age suppresses abdominal fat, plasma leptin, and plasma insulin to youthful levels in the male rat. A study of twelve weeks of melatonin treatment decreased body weight (by 7% relative to controls), abdominal fat (by 16%), blood leptin levels(by 33%), and blood insulin levels (by 25%) while increasing locomotor activity (by 19%), body temperature (by 0.5 degrees C), and morning blood corticosterone (by 154%), restoring each of these parameters toward more youthful levels. Food intake and total body fat was not changed by melatonin treatment. Melatonin-treated rats that were then put into the control group for treatment for a further 12 weeks gained body weight, whereas control rats that were put into melatonin treatment lost body weight. Food intake did not change in either group. Thus, melatonin treatment in middle age decreased body weight, abdominal body fat, blood insulin, and leptin, without altering food intake or total obesity. These results suggest that the decrease in endogenous melatonin with aging may alter metabolism and physical activity, resulting in increased body weight, obesity, and associated detrimental metabolic consequences.
   
   

   
   
   

3. Citicoline, Alzheimer's disease, and cognitive performance

   Full source: METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY, 1999, Vol 21, Iss 9, pp 633-644

   Citicoline(CDP-choline) is an endogenous intermediate in the formation of structural cell membrane phospholipids and acetylcholine in the brain. Citicoline has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke brain aging, cerebrovascular pathology, and Alzheimer's disease (AD). A 12 week study investigated the efficacy and safety of the treatment with 1,000 mg/day of citicoline vs. placebo in 30 individuals with Alzheimer disease (age 57-87 years) with mild to moderate senile dementia of the Alzheimer type. Results showed citicoline improved cognitive performance in those with Alzheimer's disease and this improvement on cognition was more pronounced in those with mild dementia. Citicoline also increased cerebral blood flow velocities in comparison with placebo; as well as diastolic velocity in the cerebral artery. Citicoline did not induce any adverse side effects or alterations in the blood. Thus, the data indicate that citicoline is well tolerated and improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in those with AD. Thus, citicoline might be a useful treatment in Alzheimer's disease. Its efficacy is greater in those with mild mental deterioration.

   
   
   

4. Grape juice inhibits human platelet aggregation

   Full source: JOURNAL OF NUTRITION, 2000, Vol 130, Iss 1, pp 53-56

   Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development, and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. A study evaluated whether grape, orange and grapefruit juices, taken daily for 7-10 days, reduce platelet activity in 10 healthy individuals (ages 26-58 years). Results showed that drinking purple grape juice for one week reduced the whole blood platelet aggregation response by 77%. Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor. Thus, the platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of heart blockage and heart attack.

   
   
   

5. Free radical stress in rheumatoid arthritis

   Full source: RHEUMATOLOGY INTERNATIONAL, 1999, Vol 19, Iss 1-2, pp 35-37

   Fasting blood samples were obtained from 24 individuals with rheumatoid arthritis (RA) and 20 control subjects. To establish blood oxidant/antioxidant status in both groups, researchers measured: 1) antioxidant potential (AOP) value, 2) nonenzymatic superoxide radical scavenger activity (NSSA), and 3) malondialdehyde (MDA) levels. Those with RA had lower AOP and NSSA but higher MDA levels than those of the control group, an indication of reduced antioxidant capacity and free radical stress. The results suggest that the antioxidant system is impaired and peroxidation reactions are accelerated in those with rheumatoid arthritis.

   
   
   

6. Carotenoids and colon cancer

   Full source: AMERICAN JOURNAL OF CLINICAL NUTRITION, 2000, Vol 71, Iss 2, pp 575-582

   Carotenoids have many biological properties that may allow them to play a role as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer. A study evaluated associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer. Data were collected from 2,410 individuals with first incident of colon cancer and from a detailed diet-history questionnaire. Lutein was inversely associated with colon cancer in both men and women (17%). The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (34%) and among those with colon tumors (35%). The associations with other carotenoids were insignificant. The major dietary sources of lutein in subjects with colon cancer and in control subjects were spinach, broccoli, lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. The data suggests that incorporating these foods into the diet may help reduce the risk of developing colon cancer.
   
   

   
   

7. Vitamin B status in those with chronic fatigue syndrome

   Full source: JOURNAL OF THE ROYAL SOCIETY OF MEDICINE, 1999, Vol 92, Iss 4, pp 183-185

   Some chronic fatigue syndrome (CFS) sufferers say they benefit from taking vitamin supplements. A study assessed the functional status for the B vitamins pyridoxine (B6), riboflavin (B2), and thiamin (B1) in 12 vitamin-untreated CFS individuals. Three vitamin-dependent activities were measured: 1) aspartate aminotransferase (AST) for B6, 2) glutathione reductase (GTR) for B2, and 3) transketolase (TK) for B1. For all three enzymes, basal activity was lower in those with CFS than in control group: AST 2.84 vs. 4.61; GTR 6.13 vs. 7.42; TK 0.50 vs. 0.60. This was also true of activated values: AST 4.91 vs. 7.89; GTR 8.29 vs. 10.0; TK 0.56 vs. 0.66. These results show evidence of reduced functional B vitamin status, particularly of vitamin B6 in chronic fatigue syndrome individuals.

   
   

8. Antioxidative effects of curcumin in liver

   Full source: BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 1999, Vol 63, Iss 12, pp 2118-2122

   Phospholipid hydroperoxides (PLOOH) level in the blood and liver of mice were measured after dietary supplementation for one week with a curcumin extract. A lower PLOOH level was found in the blood of the curcumn extract-fed mice (65-74% less than of the non-supplemented control mice). The liver lipid peroxidizability induced with iron was effectively suppressed by dietary supplementation with the curcumin extract to mice. While there was no difference in the blood lipids, the liver triglyceride concentration of the curcumin extracted mice was markedly reduced to one-half of the level in the control mice. This suggests that curcumin extract could act antioxidatively by food supplementation, and that curcumin has the ability to prevent the deposition of triglycerides in the liver.

   
   

9. Risk of heart attack with tricyclic antidepressant medications

   Full source: AMERICAN JOURNAL OF MEDICINE, 2000, Vol 108, Iss 1, pp 2-8

   Several studies have found that depression and the use of antidepressant medications are associated with an increased risk of cardiovascular disease. A study looked at whether the association between the use of antidepressant drugs and heart attack differs between the tricyclic and selective serotonin reuptake inhibitor (SSRI) classes of medication. Working, union health plan members (2,247) who received at least one prescription for an antidepressant between 1991-1992 were compared with that of 52,750 members who did not for up to 4.5 years. The primary outcome was hospitalization or death due to heart attacks.
   
   The results showed 16 heart attacks among 1,650 users of tricyclic antidepressants, 2 among 655 SSRI users. After adjustment for various factors, the risk of heart attack was 2.2 in users of tricyclic agents and only 0.8 in users of SSRIs, as compared with subjects who did not use antidepressants. Thus, the association between use of tricyclic antidepressants, but not SSRIs, with an increased risk of heart attack in the study suggests that an earlier report that there is no difference in risk between the antidepressant classes, based on short-term studies, may not apply to long-term adverse cardiovascular outcomes.
   
   

   
   

10. Low blood antioxidant activity and neurological impairment in stroke

    Full source: STROKE, 2000, Vol 31, Iss 1, pp 33-39

    Free radical stress is probably involved in nerve damage induced by ischemia-reperfusion (Ischemia is local anemia due to obstruction of the blood). A study assessed the role of antioxidant activity in cerebral ischemic stroke. Results showed that when the free radical trapping ability of the blood (but not of cerebrospinal fluid) was low, this was associated with high number of lesions and high neurological impairment. This was assessed by scores on NIH Stroke Scale, Barthel Index, and Hand Motor Score tests. The blood concentrations of vitamin C, vitamin E, and protein thiols were also associated with the degree of neurological impairment. This suggests that the antioxidant activity of blood may be an important factor providing protection from neurological damage caused by stroke-associated free radical stress.

    
    
    

11. Unfiltered coffee increases blood homocysteine

    Full source: AMERICAN JOURNAL OF CLINICAL NUTRITION, 2000, Vol 71, Iss 2, pp 480-484
    
    An elevated blood homocysteine concentration is a supposed risk factor for cardiovascular disease. A 10 week study of 64 healthy volunteers (avg. age 43) looked at the effect of coffee consumption on blood homocysteine. Unfiltered coffee was used to include the possible effects of coffee diterpenes (hydrocarbons), which are removed by filtering. Control group received water, milk, broth, tea, and chocolate drinks instead of coffee. Consumption of 1 liter, unfiltered coffee/day for 2 weeks significantly raised fasting blood homocysteine concentrations by 10%, from 12.8 to 14.0 mu mol/L. Thus, unfiltered coffee increases blood homocysteine levels in those with normal initial concentrations. It is unclear whether the effect is caused by the cholesterol-raising diterpenes present exclusively in unfiltered coffee or by factors that are also present in filtered coffee.
    
    

    
    
    

12. Oxidative stress and Alzheimer disease

    Full source: AMERICAN JOURNAL OF CLINICAL NUTRITION, 2000, Vol 71, Iss 2, pp 621S-629S

    Research in the field of molecular biology has helped to provide a better understanding of both the cascade of biochemical events that occurs with Alzheimer disease (AD) and the heterogeneous nature of the disease. One hypothesis that accounts for both the heterogeneous nature of AD and the fact that aging is the most obvious risk factor is that free radicals are involved. The probability of this involvement is supported by the fact that neurons are extremely sensitive to attacks by destructive free radicals. Furthermore, lesions are present in the brains of those with AD that are typically associated with attacks by free radicals (e.g., damage to DNA, protein oxidation, lipid peroxidation, and advanced glycosylation end products), and metals (e.g., iron, copper, zinc, and aluminum) are present that have catalytic activity that produce free radicals. beta-amyloid is aggregated and produces more free radicals in the presence of free radicals; beta-amyloid toxicity is eliminated by free radical scavengers. AD has been linked to deviations in the mitochondria (supplies energy to cell) affecting cytochrome-c oxidase. These deviations may contribute to the abnormal production of free radicals. Many free radical scavengers (e.g., vitamin E, deprenyl, and ginkgo biloba extract) have produced promising results in relation to AD, as has desferrioxamine (an iron-chelating agent) and anti-inflammatory drugs and estrogens, which also have an antioxidant effect.

    
    
    

13. Vitamin E and Alzheimer disease

    Full source: AMERICAN JOURNAL OF CLINICAL NUTRITION, 2000, Vol 71, Iss 2, pp 630S-636S

    Evidence suggests that oxidative stress is important in the pathogenesis of Alzheimer disease. In particular, beta-amyloid, which is found abundantly in the brains of those with Alzheimer disease, is toxic in neuronal cell cultures through a mechanism involving free radicals. Vitamin E prevents the oxidative damage induced by beta-amyloid in cell culture and delays memory deficits in animals. A study of 2000 IU/day of vitamin E was conducted in those with moderately advanced Alzheimer disease. The results indicated that vitamin E may slow functional deterioration leading to nursing home placement. A new clinical trial is planned that will examine whether vitamin E can delay or prevent a clinical diagnosis of Alzheimer disease in elderly persons with mild cognitive impairment.

    
    
    

14. St John's wort for depression

    Full source: ARCHIVES OF INTERNAL MEDICINE, 2000, Vol 160, Iss 2, pp 152-156

    Articles with data on the efficacy, safety, and availability of St John's wort were studied and randomized, controlled, double-blind trials were selected and assessed for methodological quality using a standardized checklist, and data on pharmacology, cost, regulation, and safety were extracted. Eight studies were identified, found to be of generally good methodological quality, and determined to provide a modest amount of data to suggest that St John's wort is more effective than placebo in the treatment of mild to moderate depression. The response rate with the use of St John's wort ranged from 23% to 55% higher than with placebo, but ranged from 6% to 18% lower compared with tricyclic antidepressants. More data are required to assess both its use in severe depression and its efficacy compared with other antidepressants. Rates of side effects were low. As a potent and useful dietary supplement, St John's wort is currently largely unregulated. However, the FDA is reviewing plans to tighten its regulation.

    
    
    

15. Fish oil protects cartilage from degradation

    Full source: JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, Vol 275, Iss 2, pp 721-724

    Supplementation with n-3 fatty acids (i.e. those present in fish oils) can modulate the expression and activity of degradative and inflammatory factors that cause cartilage destruction during arthritis. Incorporation of n-3 fatty acids (but not other polyunsaturated or saturated fatty acids) into articular cartilage chondrocyte membranes results in a dose-dependent reduction in: 1) the activity of proteoglycan degrading enzymes, and 2) the expression of inflammation-inducible cytokines (interleukin (IL)-1 alpha, tumor necrosis factor (TNF)-alpha), and cyclooxygenase (COX-2). These findings provide evidence that n-3 fatty acid supplementation can specifically affect regulatory mechanisms involved in chondrocyte gene transcription and thus shows a beneficial role for dietary fish oil supplementation in alleviating causes of arthritis.
    
    

    
    

16. Protective effects of L-arginine on heart injury

    Full source: JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION, 1999, Vol 27, Iss 1, pp 19-26

    A study looked at the effect of L-arginine (an amino acid) pre-treatment, and changes in the activities of lysosomal enzymes (serve to digest exogenous material, such as bacteria), mitochondrial enzymes and marker enzymes of cardiac function during artificially induced heart attack, using isoproterenol, in rodents. In the rats given isoproterenol, there were significant increases in serum activities of markers of cardiac function and significant reductions in the heart tissue. Activity of the lysosomal enzyme (beta-D-N-acetyl glucosaminidase) was considerably increased, and beta-galactosidase was considerably decreased in the isoproterenol-treated rats as compared with that in those given isoproterenol after pre-treatment with L-arginine. The activities of the mitochondrial enzymes in the isoproterenol-intoxicated group were significantly lower as compared with those of the L-arginine supplemented rats given isoproterenol. These results confirm the efficacy of L-arginine as a potent cardioprotective agent and the protective effect of L-arginine against isoproterenol-induced mitochondrial and lysosomal damage.

    
    

17. Kava extract for anxiety

    Full source: JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 2000, Vol 20, Iss 1, pp 84-89

    Synthetic anti-anxiety drugs are effective for treating anxiety, but they have many adverse effects. A review and analysis assessed the evidence for or against the efficacy of kava extract as a symptomatic treatment for anxiety. Systematic Literature searches were performed in the computerized databases MEDLINE, EMBASE, BIOSIS, AMED, CISCOM, and the Cochrane Library. Experts on the subject were contacted to provide further information. The results showed the superiority of kava extract over the placebo by all seven reviewed trials. The analysis of three trials suggests a significant difference (90%) in the reduction of the total score on the Hamilton Rating Scale for Anxiety in favor of kava extract. The data imply that kava extract is superior to placebo as a symptomatic treatment for anxiety. Therefore, kava extract is an herbal treatment option for anxiety that is worthy of consideration.

    
    

18. Ginkgo reduces fluid and cell injury following heat stress

    Full source: JOURNAL OF THERMAL BIOLOGY, 1999, Vol 24, Iss 5-6, Part 1, Sp. Iss. SI, pp 439-445

    Rats exposed to 4 hours of heat stress at 38 degrees C exhibited blood-brain barrier (BBB) breakdown in the brain regions, brain edema and cell damage. Pretreatment with an anti-oxidant compound Gingko biloba extract administered 50 mg/kg, for 5 days, significantly weakened BBB disruption, brain edema and cell injury. These results suggest that gingko biloba extract is neuroprotective in heat stress.
    
    

    
    

19. Melatonin reduces quinolinic acid-induced lipid peroxidation in rat brain homogenate

    Full source: METABOLIC BRAIN DISEASE, 1999, Vol 14, Iss 3, pp 165-171

    The protective effects of melatonin against the neurotoxin, quinolinic acid, were investigated in rat brain tissue. Quinolinic acid increased lipid peroxidation in a dose dependent manner. When brain tissue was co-treated with melatonin, there was a significant decrease in lipid peroxidation. The results show that melatonin may play a protective role in the brain against the neurohormone quinolinic acid, which has been identified as a causative agent in Huntington's Disease.

    
    

20. Ginkgo does not inhibit MAO A and B in living human brain

    Full source: LIFE SCIENCES, 2000, Vol 66, Iss 9, pp PL141-PL146

    Extracts of Ginkgo biloba have been reported to reversibly inhibit both monoamine oxidase (MAO) A and B in rat brain in vitro leading to speculation that MAO inhibition may contribute to some of its central nervous system effects. Positron emission tomography (PET) measured the effects of ginkgo biloba on human brain MAO A and B in 10 individuals treated for 1 month with 120 mg/day of the Ginkgo biloba extract. Blood flow and the concentration of active MAO molecules were calculated. Ginkgo biloba did not produce significant changes in brain MAO A or MAO B suggesting that mechanisms other than MAO inhibition need to be considered as mediating some of its Central Nervous System effects.

    
    
    

21. Biological effects of resveratrol

    Full source: LIFE SCIENCES, 2000, Vol 66, Iss 8, pp 663-673
    
    Resveratrol is a naturally occurring phytoalexin (plant bactericide) produced by some spermatophytes, such as grapevines, in response to injury. Since it is present in grape berry skins but not in the flesh, white wine contains very small amounts of resveratrol, compared to red wine. In red wine, its concentrations generally range between 0.1 and 15 mg/L. As a phenolic compound, resveratrol contributes to the antioxidant potential of red wine and thereby may play a role in the prevention of human cardiovascular diseases. Resveratrol has been shown to modulate the metabolism of lipids, and to inhibit the oxidation of low-density lipoproteins (LDL) and the aggregation of platelets. Also, as a phytoestrogen (plant estrogen), resveratrol may provide cardiovascular protection. It also possesses anti-inflammatory and anticancer properties.
    
    

    
    
    

22. Growth inhibition of liver cancer by retinoic acid

    Full source: ANTICANCER RESEARCH, 1999, Vol 19, Iss 4B, pp 3283-3292

    Retinoic acid, the active metabolite of vitamin A, plays a role in the growth and differentiation of a variety of normal and malignant cells. In response to retinoic acid, human liver cancer cells underwent significant growth inhibition (not associated with cell death), which reached a level of 80% in comparison with controls, after 12 days of continuous treatment. Retinoic acid also induced structural changes in these cells, indicating progression to a more differentiated phenotype, (producing more normal cells). In addition, reduced activity of alpha-fetoprotein (tumor marker for liver cancer) was found. The results may be important for the design of novel therapeutic approaches using retinoic acid for the treatment of liver tumors.

    
    
    

23. Physical activity and stroke mortality in women

    Full source: STROKE, 2000, Vol 31, Iss 1, pp 14-18

    Few studies have reported a protective effect of physical activity on stroke in women, particularly among elderly women. A study examined the association between different levels of leisure-time physical activity and stroke mortality in middle-aged and elderly women. A 10-year follow-up study looked at the mortality of 14,101 women from 1984-1986 aged greater than or equal to 50 years, free from stroke at the start. The main outcome measured was relative risk of death due to stroke, according to increasing levels of physical activity. The least active group was used as reference. In groups aged 50 to 69, 70 to 79, and 80 to 101 years, the relative risk of dying decreased with increasing physical activity, after adjustment for potentially interfering factors. In groups aged 50 to 69 and 70 to 79 years, the most active women had an adjusted relative risk of 0.42 and 0.56, respectively. In the group aged 80 to 101 years, there was a consistent negative association with physical activity; the adjusted relative risk for the most active was 0.57. Thus, physical activity was associated with reduced risk of death from stroke in middle-aged and elderly women. This association persisted after exclusion of individuals with prevalent cardiovascular and cerebrovascular disease at the start, and women who died during the first 2 years of follow-up. This strengthens the evidence that physical activity should be part of a primary prevention strategy against stroke in women.

    
    
    

24. Use of complementary health practices with prostate cancer

    Full source: CANCER, 2000, Vol 88, Iss 3, pp 615-619

    There has been increasing interest in complementary health practices among individuals, popular media, and even institutional health care providers. A study of 50 individuals undergoing radiation treatment for prostate cancer found that a surprisingly high proportion (37%) relied on complementary health practices not prescribed by physicians. In contrast, according to a separate survey of the treating physicians, the physicians believed that on average only 4% of their patients resorted to such practices. The use of complementary health practices usually continued even after the initiation of definitive treatment for prostate cancer. Those who used complementary health practices tended to have higher levels of education and income, whereas there were no differences in age, religion, perception of health status, stage of prostate cancer, or prostate specific antigen (PSA) level. Herbal remedies were the most frequently utilized, by 60% of those using complementary health practices, followed by old-lime remedies (47%), high dose vitamins (41%), chiropractic/ massage therapy and relaxation techniques (18% each), and special diets (12%).

    
    
    

25. Radiotherapy vs. surgery in prostate cancer

    Full source: CANCER, 2000, Vol 88, Iss 2, pp 398-406

    In the treatment of prostate cancer, radiotherapy and surgery are common choices of comparable efficacy. A study compared the risk of second malignancy, as being of relevance to treatment choice. Radiotherapy for prostate cancer was associated with a small, statistically significant increase in the risk of solid tumors (6%) relative to treatment with surgery. Among those who survived for greater than or equal to 5 years, the increased relative risk reached 15%, and was 34% for those surviving greater than or equal to 10 years. The most significant contributors to the increased risk in the irradiated group were cancers of the bladder, rectum, and lung, and sarcomas within the treatment area. No significant increase in rates of leukemia was noted. Radiotherapy for prostate cancer was associated with a statistically significant, although small, enhancement in the risk of second tumors, particularly for long term survivors. The estimated risk of developing a radiation-associated second malignancy was 1 in 290 for all those with prostate cancer treated with radiotherapy, increasing to 1 in 70 for long term survivors (greater than or equal to 10 years). Improvements in radiotherapeutic techniques, along with diagnosis at younger ages and earlier stages, are resulting in longer survival times for those with prostate cancer. Because of the long latency period for radiation-induced tumors, this may result in radiation-related second malignancy risk becoming a more significant issue.
    
    

    
    

26. Caloric restriction reduces heat induced cellular damage

    Full source: FASEB JOURNAL, 2000, Vol 14, Iss 1, pp 78-86

    Adult-onset, long-term caloric restriction (CR) prolongs maximum life span in laboratory rodents. A study investigated the influence of CR and aging on stress tolerance in old rats exposed to an environmental heating protocol for 2 days. Researchers hypothesized that CR would increase the tolerance to heat by reducing stress to the cells and thus reducing subsequent accrual of free radical injury. Results showed that all calorically restricted rats survived both heat exposures compared with only 50% of their control-fed counterparts. CR also decreased heat-induced free radical generation, stress protein accumulation, and cellular injury in the liver. In addition, heat stress stimulated a high activity of the antioxidant enzymes manganese-containing superoxide dismutase and catalase, along with strong catalase activity in liver samples from rats subjected to CR. In contrast, in the control-fed group, the induction of antioxidant enzymes due to stress was blunted, and catalase activity was unchanged from optimal temperature conditions. These data suggest that caloric restriction reduces cellular injury and improves heat tolerance of old animals by lowering free radical production and preserving the ability of cells to adapt to stress through antioxidant enzyme induction and translocation of these proteins to the nucleus.

    
    

27. Skin collagen glycation predict early death in mice

    Full source: FASEB JOURNAL, 2000, Vol 14, Iss 1, pp 145-156

    In 1998, the National Institute on Aging launched a 10-year program aimed at identification of biomarkers of aging. Pentosidine, an advanced glycation product, formed in the skin collagen at a rate inversely related to maximum life span across several mammalian species. Researchers investigated the hypothesis that longitudinal determination of glycation and glycoxidation rates in skin collagen could predict longevities in mice fed unlimited amounts (UL) and caloric restricted (CR) mice. CR vs. UL significantly increased both means (34 vs. 27 months) and maximum (47 vs. 31 months) life spans. Skin collagen levels of furosine (indicator of glycation) were similar to 2.5-fold greater than carboxymethyllysine (CML) levels greater than pentosidine (glycoxidation products). Individual accumulation rates of gylcation were significantly inhibited by CR vs. UL for all parameters and in all cases varied inversely with longevity. The incidence of three tissue pathologies (lymphoma, dermatitis, and seminal vesiculitis) was found to be weakened by caloric restriction. The seminal vesiculitis was associated significantly in time with longevity (46%). The finding that markers of skin collagen glycation and glycoxidation rates can predict early deaths in UL and CR mice strongly suggests that an age-related deterioration in glucose tolerance is a process that can determine life span.

    
    

28. Low cholesterol level and death due to cancer

    Full source: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2000, Vol 5, Iss 2, pp 201-205

    Studies indicate that low serum total cholesterol level may increase the risk of death due to cancer, mainly lung cancer. A study evaluated serum levels of total cholesterol (TC) and triglycerides (TG) in those with squamous cell and small cell lung cancer. Lung cancer patients (135) had higher rate of hypocholesterolemia (abnormally small amounts of cholesterol in the circulating blood) and lower TC and TG levels than the healthy control group (39). TG level was lower only in those with squamous cell lung cancer.