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Life Extension Magazine

LE Magazine September 1999

MEDICAL UPDATES
Studies from throughout the world that can help you live longer

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September 1999
Table Of Contents
 
  1. Vitamin E lack linked to memory loss
  2. Piracetam and metabolic reactions in elderly
  3. Progesterone levels and prognosis in breast cancer
  4. Cisplatin chemotherapy reduces antioxidants in blood
  5. Chemopreventive effect of curcumin in colon cancer
  6. Silymarin protects against tumors
  7. Phosphatidylserine necessary for immune function
  8. Phytoestrogens inhibit cell growth
  9. Low vitamin E status risk factor for diabetes
  10. Age-related decrease in cardiac tolerance to oxidative stress
  11. The cholinergic hypothesis of Alzheimer's disease: a review of progress
  12. Protective effect of vitamin E on ovaries
  13. Antioxidant defense system of elderly diabetic men
  14. Growth hormone deficiency and cardiovascular risk
  15. Aging and growth hormone status
  16. Uses of GH releasing substances in adults
  17. Garlic, onion and cereal as protection for breast cancer
  18. Screening decreases prostate cancer death
  19. Human salivary tea catechins in cancer prevention

  1. Vitamin E lack linked to memory loss

    Full source: American Journal of Epidemiology 1999;150:37-44

    Free radicals, produced during normal metabolic processes, cause oxidative stress. Oxidative stress has been implicated both in the aging process and in the pathological changes associated with Alzheimer's disease. Antioxidants help provide protection against free radical damage. In this study, investigators examined the association between blood levels of antioxidants, including vitamins A, C and E, and selenium, and memory in a multiethnic population of senior citizens. The researchers examined 4,809 people aged 60 or older between 1988 and 1994. They found a connection between poor memory and low blood levels of vitamin E. Overall, 7% of the group had poor memory. These people were at least twice as likely to report problems managing their money or preparing meals. Among those with vitamin E levels lower than 4.8 per unit of cholesterol, 11% had poor memory. In contrast, just 4% of people with levels higher than 7.2 had memory problems. Increasing levels of vitamin E were associated with better memory performance for this ethnically diverse elderly population. Among those who said they did not eat enough food or skipped meals, almost 20% had poor memory, as opposed to 7% among people who ate regularly. The researchers report that they found no connection between the other antioxidants and memory loss. Most previous studies have not found a link between vitamin deficiencies and memory. However, the researchers noted, many of these studies had a limited range of subjects who were mostly Caucasian, well-educated and higher income levels -- all factors linked to better memory retention.



  2. Piracetam and metabolic reactions in elderly

    Full source: Russian Federation Kardiologiya (Russian Federation) 1995, 35/11 (30-34)

    Piracetam (2.4-5.2 g/day) was added to conventional therapy in 100 elderly patients with ischemic heart disease and stable effort angina. Complex study of changes of some hormonal and metabolic indices showed that piracetam caused decreases in plasma concentrations of low density lipoprotein (LDL) cholesterol and triglycerides and reduction in degree of hyperglycemia and duration of hyperinsulinemia during glucose tolerance test. Dynamics of blood contents of growth hormone, testosterone, cortisol, ACTH, protein- and peptide-bound oxyproline was indicative of activation of anabolic processes. Piracetam also abolished dysbalance of cyclic nucleotide in blood.



  3. Progesterone levels and prognosis in breast cancer

    Full source: Br J Cancer 1996 Jun;73(12):1552-5

    Several studies have now shown that women with operable breast cancer undergoing tumor removal during the luteal phase of the menstrual cycle have a better prognosis than those having surgery during the follicular phase. Between 1975 and 1992 blood samples were taken and analyzed for both estrogen (E2) and progesterone (P) from 289 premenopausal women within 3 days of tumor excision. All were treated by either modified radical mastectomy or breast conservation and the date of last menstrual period (LMP) was known in 239 (80%) cases. Because of the wide individual variation in E2 levels, there was no clear relationship between E2 and LMP. There was no significant association between E2 and survival. However, those cases with a progesterone level of 4 ng ml-1 or more had a significantly better survival than those with a level less than 4 ng ml-1. This was especially clear in node-positive patients. The study has confirmed that a raised level of progesterone at the time of tumor excision is associated with an improvement in prognosis for women with operable breast cancer. Thus, biorhythm or menstrual cycle timing is important for survival in women undergoing breast cancer surgery.



  4. Cisplatin chemotherapy reduces antioxidants in blood

    Full source: Annals of Oncology, 1998, Vol 9, Iss 12, pp 1331-1337

    Antioxidants protect the body against cellular oxidative damage and thus some of the adverse effects induced by cisplatin (a chemotherapeutic agent with antitumor activity). The effect of cisplatin-combination chemotherapy on concentrations of blood antioxidants was studied in 36 cancer patients, including osteosarcoma and testicular carcinoma patients. Eight to 15 days after the start of each cytostatic drug infusion, concentrations of various plasma antioxidants were measured and compared to pretreatment values: vitamin C and E, uric acid and ceruloplasmin levels fell significantly and returned to baseline levels before the start of the next chemotherapy cycle. Levels of the antioxidants bilirubin, albumin and the ratio vitamin E/cholesterol + triglycerides measured three weeks after the start of chemotherapy significantly decreased compared to pretreatment levels and remained low thereafter. Thus, the Cisplatin-combination chemotherapy induced fall in blood antioxidant levels may reflect a failure of the antioxidant defense mechanism against oxidative damage induced by commonly used anticancer drugs. This probably results from consumption of antioxidants caused by chemotherapy induced-oxidative stress as well as renal loss of water-soluble, small molecular weight antioxidants such as uric acid.



  5. Chemopreventive effect of curcumin in colon cancer

    Full source: Cancer Research, 1999, Vol 59, Iss 3, pp 597-601

    Curcumin, having both antioxidant and anti-inflammatory properties, inhibits chemically induced carcinogenesis in the skin, forestomach, and colon when it is administered during initiation and/or postinitiation stages. This study investigated the chemopreventive action of curcumin when it is administered (late in the premalignant stage) during the promotion/progression stage of colon carcinogenesis in male rats. We also studied the modulating effect of this agent on apoptosis in the tumors. The administration of 0.2% curcumin during both the initiation and postinitiation periods significantly inhibited colon tumorigenesis (production of a new growth); administration of 0.2 % and of 0.6% of the curcumin significantly suppressed the incidence and multiplicity of malignant cancer of the colon. The degree of inhibition of colon cancers was dependent on dose. Administration of curcumin increased death in the colon tumors as compared to colon tumors in the groups receiving the control diet. Thus, chemopreventive activity of curcumin is observed when it is administered prior to, during, and after carcinogen treatment as well as when it is given only during the promotion/progression phase (starting late in premalignant stage) of colon carcinogenesis.



  6. Silymarin protects against tumors

    Full source: Cancer Research, 1999, Vol 59, Iss 3, pp 622-632

    Silymarin, a flavonoid isolated from milk thistle, is used clinically in Europe and Asia as an antihepatotoxic agent, largely due to its strong antioxidant activity. This study assessed the protective effect of silymarin on tumor promotion in mouse skin cancer growth. Silymarin provided highly significant protection against tumor promotion in mouse skin. Application of silymarin in stage I and stage II tumor promotion in mouse skin resulted in an exceptionally high protective effect during stage I tumor promotion, showing 74% protection against tumor incidence, 92% protection against tumor multiplicity, and 96% protection against tumor volume. In other studies, silymarin significantly inhibited: (a) TPA-induced skin edema, epidermal hyperplasia, and proliferating cell nuclear antigen-positive cells; (b) DNA synthesis; and (c) epidermal lipid peroxidation, the early markers of TPA-caused changes that are associated with tumor promotion. These results suggest that silymarin possesses exceptionally high protective effects against tumor promotion, primarily targeted against stage I tumors, and that the mechanism of such effects may involve inhibition of edema (excessive amount of cell fluid), hyperplasia (increase in number of cells), proliferation index, and oxidant state.



  7. Phosphatidylserine necessary for immune function

    Full source: Cell Death and Differentiation, 1999, Vol 6, Iss 2, pp 183-189

    Although different macrophages exploit different cell surface receptors to recognize apoptotic (dying) lymphocytes (immune cells), indirect evidence suggested that the phosphatidylserine (PS) that appears on the surface of lymphocytes undergoing apoptosis participates in specific recognition by all types of macrophages. To test this possibility directly, annexin V, a protein that specifically binds to PS, was used to mask this phospholipid on the apoptotic cell surface. Preincubation of apoptotic lymphocytes with annexin V blocked phagocytosis (cell ingestion) by elicited mouse macrophages in tissue on abdominal cavity, macrophages of the mouse cell, and mouse bone marrow macrophages. Similarly, annexin V was able to inhibit phagocytosis of red blood cells, another target cell upon which PS is exposed. These results demonstrate directly that macrophages of all types depend on the phosphatidylserine exposed on the surface of apoptotic lymphocytes for recognition and phagocytosis.



  8. Phytoestrogens inhibit cell growth

    Full source: Hypertension, 1999, Vol 33, Iss 1, Part 2, Suppl. S, pp 177-182

    Estrogens are known to induce cardioprotective effects by inhibiting smooth muscle cell (SMC) growth and new growth formation, However, the use of estrogens as cardioprotective agents is limited by carcinogenic effects in women and feminizing effects in men. If noncarcinogenic and nonfeminizing estrogen-like compounds, such as natural phytoestrogens, afford cardioprotection, this would provide a safe method for prevention of cardiovascular disease in both men and women. This study evaluated and compared in human aortic SMCs the effects of phytoestrogens on serum-induced proliferation, collagen synthesis and total protein synthesis, and on induced cell migration. Phytoestrogens inhibited proliferation, collagen and total protein synthesis, migration, and MAP kinase activity in a concentration-dependent manner and in the following order of potency, respectively, biochanin, genistein, equol, daidzein, and formononetin. The study provides the first evidence that in human aortic SMCs phytoestrogens inhibit mitogen-induced proliferation, migration and extracellular matrix synthesis and inhibit/downregulate MAP kinase activity. Thus, phytoestrogens may confer protective effects on the cardiovascular system by inhibiting vascular remodeling and new inner formation of tissue. It may therefore be useful as a safer substitute for feminizing estrogens in preventing cardiovascular disease in both women and men.



  9. Low vitamin E status risk factor for diabetes

    Full source: Journal of Internal Medicine, 1999, Vol 245, Iss 1, pp 99-102

    This study looked at the association of vitamin E status with occurrence of insulin-dependent diabetes mellitus (IDDM) within a 21-year follow-up period. Serum alpha-tocopherol concentration at the baseline examination was oppositely associated with IDDM occurring 4-14 years later. The risk of IDDM between the highest and lowest thirds of the vitamin concentration was 0.12 (95% confidence interval = 0.02-0.85). The finding corroborates the hypothesis of a protective effect of vitamin E against development of insulin-dependent diabetes mellitus. Because of the relatively old age of the patients in the present population, further, epidemiological studies on the topic are warranted.



  10. Age-related decrease in cardiac tolerance to oxidative stress

    Full source: Journal of Molecular and Cellular Cardiology, 1999, Vol 31, Iss 1, pp 227-236

    Free radical-mediated injury has been implicated in the process of cardiac aging. The tolerance to oxidative stress of hearts from rats of different age was investigated. Infusion with the free radical hydrogen peroxide resulted in a significantly larger increase in end-diastolic pressure in hearts of 6- and 12-month-old rats than 3 month olds. In addition, developed pressure and rate-pressure product decreased more evidently in 12-month-old hearts. Arrhythmia analysis showed higher score in hearts of 12- and 6-month-old rats with respect to 3-month-old animals. Cardiac release of oxidized glutathione, (an index of the ability of the heart to inactivate oxygen metabolites) was significantly lower in hearts from rats of 6 and 12 months than in younger animals. Finally, cardiac concentrations of the scavenger enzymes glutathione peroxidase and manganese-superoxide dismutase also significantly decreased with age. Thus, rat heart metabolic and functional tolerance toward oxidative stress decreases with age. This phenomenon may contribute to the development of cardiovascular alterations with increasing age.



  11. The cholinergic hypothesis of Alzheimer's disease: a review of progress

    Full source: Journal of Neurology Neurosurgery and Psychiatry, 1999, Vol 66, Iss 2, pp 137-147

    Alzheimer's disease is one of the most common causes of mental deterioration in elderly people, accounting for around 50%-60% of the overall cases of dementia among persons over 65 years of age. The past two decades have witnessed a considerable research effort directed towards discovering the cause of Alzheimer's disease with the ultimate hope of developing safe and effective pharmacological treatments. This article examines the existing scientific applicability of the original cholinergic hypothesis of Alzheimer's disease by describing the biochemical and histopathological changes of neurotransmitter markers that occur in the brains of patients with Alzheimer's disease both at postmortem and neurosurgical cerebral biopsy and the behavioral consequences of cholinomimetic drugs and cholinergic lesions. Such studies have resulted in the discovery of an association between a decline in learning and memory, and a deficit in excitatory amino acid (EEA) neurotransmission, together with important roles for the cholinergic system in attentional processing and as a modulator of EAA neurotransmission. Accordingly, although there is presently no "cure" for Alzheimer's disease, a large number of potential therapeutic interventions have emerged that are designed to correct loss of presynaptic cholinergic function. A few of these compounds have confirmed efficacy in delaying the deterioration of symptoms of Alzheimer's disease, a valuable treatment target considering the progressive nature of the disease. Indeed, three compounds have received European approval for the treatment of the cognitive symptoms of Alzheimer's disease, first tacrine and more recently, donepezil and rivastigmine, all of which are cholinesterase inhibitors (acetylcholinesterase destroys acetylcholine in the brain).



  12. Protective effect of vitamin E on ovaries

    Full source: Journal of Reproduction and Fertility, 1998, Vol 114, Iss 2, pp 341-346

    Cryopreservation of tissues of the ovary is a potential strategy for the preservation of fertility in patients undergoing systemic chemotherapy and pelvic radiotherapy. Non-vascular implants are first subjected to a period of ischemia (obstruction of the blood supply) before revascularization and are, therefore, vulnerable to ischemia reperfusion (myocardial impairment) injury from free radicals. This study investigated ischemia-reperfusion injury during the first week after surgery in mouse ovarian grafts and human ovarian xenografts in mice with severe combined immune deficiency by measuring total lipid peroxides and malondialdehyde concentrations. The effects of administering an antioxidant, vitamin E, on these concentrations were tested. Products of lipid peroxidation were higher in non-supplemented mouse autografts compared with control ovaries, and were significantly reduced on day 3 by vitamin E administration. There was a significant reduction in lipid peroxidation with vitamin E administration. These results correspond to a significantly greater total follicle survival in the grafts of the supplemented group (45 versus 72%. This suggests that antioxidant treatment improves the survival of follicles in ovarian grafts by reducing ischemia-reperfusion injury.



  13. Antioxidant defense system of elderly diabetic men

    Full source: Archives of Gerontology and Geriatrics, 1999, Vol 28, Iss 1, pp 65-83

    Levels of antioxidants, activities of free radical scavenging enzymes and extent of lipid peroxidation were determined in the blood of 37 elderly diabetic men and 30 control elderly men. Sixteen had cardiovascular disease (CVD) and 14 did not. The mean ages of the men were 66 and those of the control group were 69. Serum glucose levels of diabetic men were 213 mg/dl and that of control subjects were 95 mg/dldl. Among the diabetic men, 13 men were obese, 26 men had poor control of diabetes and 25 men had retinopathy. The results show that diabetic men had significantly lower blood reduced glutathione levels and red blood cell (RBC) superoxide dismutase activity when compared to control groups with or without CVD. There were no significant differences in plasma vitamin E levels and the activities of catalase and glutathione peroxidase in RBC among the three groups. The extent of lipid peroxidation was highest in diabetic patients, intermediate in controls with CVD, and lowest in controls without CVD. The results suggest that a decline of endogenous antioxidant defense capability contributes to oxidative stress in the diabetic elderly patients. Dietary survey showed that there were no differences in the nutrient intakes of diabetic and control groups. It appears that individual dietary advice is needed for a large portion of diabetic patients in view of their poor glycemic control, hypertriglyceridemia and obesity.



  14. Growth hormone deficiency and cardiovascular risk

    Full source: Baillieres Clinical Endocrinology and Metabolism, 1998, Vol 12, Iss 2, pp 199-216

    It is now recognized that growth hormone (GH) deficiency in adults represents a distinct clinical syndrome that encompasses reduced psychological well-being as well as specific metabolic abnormalities. The latter features, which include hypertension, central obesity, insulin resistance, dyslipidemia (large amount of fats in the blood) and coagulopathy (a problem with blood coagulation), closely resemble those of metabolic insulin resistance syndrome. The increased cardiovascular morbidity and mortality demonstrated in these GH-deficient (GHD) adults reinforce the close association between the two syndromes. Replacement of GH in GHD adults has resulted in a marked reduction of obesity and significant reduction in total cholesterol. However, there's been little change in other-risk factors such as insulin resistance and dyslipidemia. The persistent insulin resistance and dyslipidemia, together with the elevation of blood insulin levels with GH replacement are of concern. Long-term follow-up data are required to assess the impact of GH replacement on the cardiovascular illness and death of GHD adults, as well as further exploration of the appropriateness of the GH dosage regimens currently being employed.



  15. Aging and growth hormone status

    Full source: Baillieres Clinical Endocrinology and Metabolism, 1998, Vol 12, Iss 2, pp 281-296

    Organic growth hormone (GH) deficiency in adults results in many adverse changes similar to the changes which occur in humans with increasing age. The secretion of GH from the anterior pituitary declines with increasing age. This observation, together with the changes in body composition associated with organic GH deficiency in adults, has led to the suggestion that the elderly without hypothalamic-pituitary disease are GH deficient and may benefit from GH therapy. The impact of organic disease of the hypothalamic-pituitary axis in the elderly may result in a reduction in GH secretion of up to 90%. This reduction in GH secretion is sufficient to cause a fall in the serum insulin-like growth factor-1 (IGF-1) concentration, abnormal body composition and abnormal bone turnover, although bone mineral density is unaffected. These changes are distinct from those associated with the hyposomatotropism of the elderly, but are less severe than those seen in younger adults with organic GH deficiency. In this article, the author discusses the effects of organic GH deficiency in elderly subjects and the potential effects of GH replacement therapy. Also examined is the potential for GH therapy to correct some of the detrimental effects of the aging process.



  16. Uses of GH releasing substances in adults

    Full source: Baillieres Clinical Endocrinology and Metabolism, 1998, Vol 12, Iss 2, pp 341-358

    Is there any alternative test equal to, or even better than, the insulin-tolerance test.(ITT), the so-called gold standard, for the diagnosis of growth hormone deficiency (GHD) in adults and the elderly? The answer is YES. In fact, when combined with arginine or pyridostigmine, growth hormone-releasing hormone (GHRH) becomes one of the most potent and reproducible tests for distinguishing patients with severe GHD from normal subjects. Owing to its tolerability and its suitability for use in the elderly, the GHRH + arginine test is the best alternative choice and is at least as sensitive as the ITT provided that appropriate cut-off limits are given. Is there any therapeutic approach alternative to recombinant human growth hormone (rhGH) for adult and elderly patients with GHD and/or for the somatopause? At present, the answer is NO. Growth hormone (GH)-releasing substances need the functional integrity of somatotroph cells to induce the release of growth hormone. Probably only patients with childhood-onset, isolated GHD could benefit from treatment with GHRH or growth hormone secretagogues (GHS). Whenever restoration of the activity of the GH/insulin-like growth factor-1 (IGF-1) axis in the elderly would be of use, GHRH and/or GH secretagogues would be good candidates. In fact, the existence of a considerable pool of releasable growth hormone has been demonstrated in the elderly.



  17. Garlic, onion and cereal as protection for breast cancer

    Full source: European Journal of Epidemiology, 1998, Vol 14, Iss 8, pp 737-747

    The role of diet on breast cancer risk was investigated in a case-control study of 345 patients diagnosed with primary breast cancer between 1986 and 1989 in the north-east of France. For each case, one control was matched for age and socio-economic status. The dietary history questionnaire consisted of a self-administered food frequency questionnaire, a 6-day food diary and an energy expenditure record. It also elicited personal characteristics and medical history. While taking into account total caloric intake and established risk factors, breast cancer risk was shown to decrease as consumption of fiber, garlic and onions increased. This study also supports the evidence that saturated fat intake and breast cancer risk is associated in post-menopausal women. On the other hand, it suggests that unsaturated fat intake could lower the risk in the same subgroup. These findings on protective factors of breast cancer could prompt effective preventive measures and warrant further experimental investigations.



  18. Screening decreases prostate cancer death

    Full source: Prostate, 1999, Vol 38, Iss 2, pp 83-91

    This study in Quebec City in November 1988 of 46,193 men aged 45 to 80 years assessed the impact of prostate cancer screening on cause-specific death. They were randomized between screening and no screening. The deaths due to prostate cancer numbering 137 occurred between 1989 and 1996, inclusively, in the 38,056 unscreened men while only 5 deaths were observed among the 8,137 screened individuals. This showed a 3.25 odds ratio in favor of screening and early treatment. If PSA screening is started at the age of 50 years (or 45 years in the higher risk population), annual or biannual PSA alone is highly efficient to identify the men who are at high risk of having prostate cancer. Coupled with treatment of localized disease, this approach demonstrates, for the first time, that early diagnosis and treatment permits a dramatic decrease in deaths from prostate cancer.



  19. Human salivary tea catechins in cancer prevention

    Full source: Cancer Epidemiology Biomarkers & Prevention, 1999, Vol 8, Iss 1, pp 83-89

    The possible application of tea in the prevention of oral and esophageal cancers prompted this study. The levels of tea catechins in saliva were determined in six human volunteers after drinking tea. Saliva samples were collected after thoroughly rinsing the mouth with water. After drinking green tea preparations equivalent to two to three cups of tea, peak saliva levels of catechin components, epigallocatechin (EGC), EGC-3-gallate (EGCG), and epicatechin (EC) were observed after a few minutes. These levels were 2 orders of magnitude higher than those in the blood. The elimination half-life (period in which substance decreases by half); of the salivary catechins was 10-20 min, much shorter than that of the blood. Holding a tea solution in the mouth for a few minutes without swallowing produced even higher salivary catechin levels, but taking tea solids in capsules resulted in no detectable salivary catechin level. The results of the study suggested that slowly drinking tea is a very effective way of delivering rather high concentrations of catechins to the oral cavity and then the esophagus.