LE Magazine January 2002
Studies from throughout the world that can help you live longer
January 2002 Table of Contents
1. Micronutrients and innate immunity
Micronutrients such as zinc, selenium, iron, copper, beta-carotene, vitamins A, C and E, and folic acid can influence several components of innate immunity. Select micronutrients play an important role in alteration of oxidant-mediated tissue injury, and phagocytic cells produce reactive oxidants as part of the defense against infectious agents. Thus, adequate micronutrients are required to prevent damage of cells participating in innate immunity. Deficiencies in zinc and vitamins A and D may reduce natural killer cell function, whereas supplemental zinc or vitamin C may enhance their activity. The specific effects of micronutrients on neutrophil functions are not clear. Select micronutrients may play a role in innate immunity associated with some disease processes. Future studies should focus on issues such as age-related micronutrient status and innate immunity, alterations of micronutrients during diseases and their effect on innate immunity, and the mechanisms by which micronutrients alter innate immunity.
JOURNAL OF INFECTIOUS DISEASES, 2000, Vol 182, Suppl. 1, pp S5-S10
2. Deficiency of folic acid and vitamin B-12 (cobalamin)
The deficiency of folic acid or vitamin B-12 (cobalamin) is recognized by the presence of an anemia (reduction below normal of the number of red blood cells) resulting from changes in the bone marrow. A new view has identified both new mechanisms for altered folic acid and vitamin B-12 status and new interrelationships. These include: 1) altered types of absorption, 2) a changing pattern of neurologic deficits, 3) an increased risk of vascular lesions and 4) an important relationship with the mechanisms of tumor development of how these newer characterizations relate to issues of tumor development in the nonpregnant woman and to issues in pregnancy such as the potential for developmental abnormalities of the fetal nervous system.
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 2000, Vol 14, Iss 5, pp 1079-+
3. Vitamin E and coronary heart disease
Vitamin E is thought to be effective in preventing atherosclerosis. A study looked at the degree of association between vitamin E and coronary heart disease (CHD) in 62 coronary atherosclerotic individuals (age 65) and sex-matched controls. Results showed that blood levels of vitamin E standardized for cholesterol and lipid concentrations were significantly lower in coronary patients than in controls (4.35 vs. 4.82 mmol/mol) for cholesterol-adjusted vitamin E and 2.35 vs. 2.66 for lipid-adjusted vitamin E, respectively. In the low-density lipoprotein (LDL) fraction, only cholesterol-standardized vitamin E was significantly lower in coronary patients than controls (3.84 vs. 4.41). This association between vitamin E and CHD remained unchanged independent of age, sex, smoking habit, hypertension and diabetes. In CHD patients, a lower lipid-adjusted vitamin E was associated with enhanced LDL susceptibility to oxidation. This confirms that vitamin E plays a role in preventing atherosclerosis.
CLINICAL CHEMISTRY, 2000, Vol 46, Iss 9, pp 1401-1405
4. Effects of green tea on spore-forming bacteria
The inhibitory action of tea polyphenols towards the development and growth of bacterial spores was examined. The heat resistance of B stearothermophilus spores (a thermophilic spore-forming bacterium) was reduced by the addition of tea polyphenols. Clostridium thermoaceticum, an anaerobic spore-forming bacterium, also exhibited reduced heat resistance of its spores in the presence of tea polyphenols. Epigallocatechin gallate, the main component of tea polyphenols, showed strong activity against both B stearothermophilus and C thermoaceticum. The heat resistance of these bacterial spores was more rapidly decreased by the addition of tea polyphenols at high temperatures.
JOURNAL OF BIOSCIENCE AND BIOENGINEERING, 2000, Vol 90, Iss 1, pp 81-85
5. Garlic enhances circulatory antioxidants
The protective effect of garlic on circulatory lipid peroxidation and antioxidants was investigated in rodents during induced cancer. Enhanced lipid peroxidation in the circulation of tumor-bearing animals was accompanied by a significant decrease in the levels of vitamin C and E, reduced endogenous antioxidants such as glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. However, the administration of garlic extract significantly decreased lipid peroxidation and the simultaneous depletion of antioxidants. Thus, garlic may exerts its protective effects by decreasing circulatory lipid peroxides and enhancing antioxidants.
JOURNAL OF ETHNOPHARMACOLOGY, 2000, Vol 72, Iss 3, pp 429-433
6. Effects of UVA and UVB rays on antioxidant enzymes in the eye
A study examined the effects of UVA and UVB rays on antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) in the cornea. The corneas of albino rabbits were irradiated with a UV lamp generating UVA or UVB rays, 1 x daily for 5 min, from a distance of 0.03 meters, over 4 days (shorter procedure) or 8 days (longer procedure). In contrast to UVA rays, which did not cause significant disturbances, UVB rays changed the activities of antioxidant enzymes. The longer the repeated irradiation with UVB rays was performed, the greater the decrease in antioxidant enzymes. The shorter procedure caused a more profound decrease of glutathione peroxidase and catalase than of superoxide dismutase. (Superoxide dismutase is an enzyme scavenging superoxide radical that produces hydrogen peroxide during the dismutation reaction of a superoxide free radical). This may contribute to an insufficient division of hydrogen peroxide at the corneal surface and danger to the cornea from free radical damage. After the longer procedure (UVB rays), the activities of all antioxidant enzymes were very low or completely absent. Thus, repeated irradiation of the cornea with UVB rays causes a deficiency in antioxidant enzymes in the cells of the cornea, which very probably contributes to the damage of the cornea (and possibly also deeper parts of the eye) from UVB rays and the free radicals generated by them.
HISTOLOGY AND HISTOPATHOLOGY, 2000, Vol 15, Iss 4, pp 1043-1050
7. Inhibition of hepatitis by aminoguanidine
Aminoguanidine is an inhibitor of inducible nitric oxide synthase (iNOS) and has potential clinical use. Mice were treated with certain antibodies that increased alanine aminotransferase activity in the bloodstream. This elevation was inhibited by pretreatment of mice with aminoguanidine. The antibody-induced elevation of caspase-3 activity was inhibited by aminoguanidine. Thus, aminoguanidine prevents anti-Fas antibody-induced hepatitis by affecting the programmed cell death pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY, 2000, Vol 403, Iss 3, pp 277-280
8. DHEA reduces neurotoxic effects of corticosterone
Glucocorticoids are toxic to hippocampal (brain) neurons (nerve cells). We report here that DHEA protects neurons of primary hippocampal cultures against the toxic effects of corticosterone. Corticosterone is a steroid that induces the deposit of glycogen in the liver, salt conservation and potassium excretion. Corticosterone added for 24 hours to embryonic cultures rat hippocampus resulted in significant neurotoxicity. Corticosterone-induced toxicity was prevented by co-treatment of the cultures with 20-500 nM of DHEA. These experiments show that DHEA has potent anti-glucocorticoid actions on the brain, and can protect brain nerve cells from glucocorticoid-induced neurotoxicity.
NEUROSCIENCE, 1999, Vol 89, Iss 2, pp 429-436
9. Curcumin and cancer prevention
Curcumin, a dietary pigment phytopolyphenol, is also a potent inhibitor of tumor promotion induced by TPA (carcinogen) in mouse skin. Treatment with 15 or 20 mu M curcumin for 15 minute inhibited TPA-induced protein kinase C (PKC) activity by 26% to 60%. Curcumin inhibited the molecular mechanisms of TPA-induced tumor promotion by suppression of PKC activity and nuclear oncogene expression.
JOURNAL OF CELLULAR BIOCHEMISTRY , 1997, Suppl. 28-29, pp 39-48
10. Green tea benefits digestive tract
Tea catechins undergo various metabolic changes after they are taken orally, though a large percentage is excreted intact with the feces. Epidemiological studies suggest a protective effect of tea against various human cancers, including colon and rectum. The bactericidal property of tea catechins plays several roles in the digestive tract. In the small intestine, catechins inhibit alpha-amylase activity, and a certain amount is absorbed into the portal vein. Although catechins are bactericidal, they do not affect lactic acid bacteria. Including tea catechins in the diet for several weeks decreases putrefactive products and increases organic acids by lowering pH. These changes were achieved with 100 mg of tea catechins (equivalent to two to five cups of green tea) three times daily with meals for three weeks. When catechin administration ceased, the effects reversed after one week. Catechins should be considered further in colon carcinogenesis studies.
JOURNAL OF CELLULAR BIOCHEMISTRY, 1997, Suppl. 27, pp 52-58
11. DHA protects small intestine in mice
Oral administration of methotrexate (MTX) to mice causes the damage of the small intestine. The permeability of poorly absorbable compound (FITC-dextran) through the small increased remarkably in the MTX-treated mice. However, oral administration of DHA (docosahexaenoic acid) ethyl ester protected the small intestine from the increase in the small intestinal permeability induced by the MTX treatment. The MTX treatment decreased retinol concentration in plasma of mice and the coadministration of DHA maintained its concentration to the level of control mice. The present study showed that DHA protected the small intestine of mice from the MTX-induced damage.
LIFE SCIENCES, 1998, Vol 62, Iss 15, pp 1333-1338
12. Neuroprotective strategies for Alzheimer's disease
Alzheimer's disease (AD) is neuron (nerve cell) degeneration in the brain resulting in dysfunction of the synapses between nerve cells. Age-related increases in cellular oxidative stress, and impairment of energy metabolism, result in disruption of calcium homeostasis (stability) of the nerve cells and their increased vulnerability to excitotoxicity and death. Inherited forms of AD that result from mutations in the beta-amyloid precursor protein (APP) and presenilins accelerate the neurodegenerative cascade by increasing production and depositing neurotoxic forms of amyloid beta-peptide and by upsetting calcium homeostasis. 1) Dietary restriction (DR; reduced calorie intake with maintained nutrition) extends life span of rodents and (probably) humans. DR increases resistance of neurons to dysfunction and degeneration, and improves behavioral outcome, in experimental models of AD and other age-related neurodegenerative disorders by a mechanism involving a mild stress response. 2) Telomerase, a specialized reverse transcriptase, has been proposed to possess anti-aging properties. The catalytic subunit of telomerase (TERT) is active in neurons throughout the brain during development, but is absent from neurons in the adult brain. TERT exhibits neuroprotective properties in experimental models of neurodegenerative disorders suggesting that inducing telomerase in neurons may protect against age-related neurodegeneration. 3) The exciting and exploding field of stem cell research suggests methods for replacing damaged or lost brain cells in many different neurological disorders.
EXPERIMENTAL GERONTOLOGY, 2000, Vol 35, Iss 4, pp 489-502
13. Component of red grapes stops growth of leukemia cells
Resveratrol, (an antioxidant present in red grapes) in the concentration range of 20 mu M and above stopped the growth of lymphocytic leukemia cells during the S-Phase of the growth cycle. This growth inhibition was not impeded by antagonist antibodies.
CELL DEATH AND DIFFERENTIATION, 2000, Vol 7, Iss 9, pp 834-842
14. Prevention of cell adhesion in treatment of cancer
The formation of new blood vessels, called angiogenesis, is critical for a tumor to grow beyond a few mm (3) in size. Cancer cells form a matrix that promotes cell adhesion or stickiness, migration, proliferation and survival. The building and coming apart of this matrix closely resemble processes that occur during coagulation (formation of a clot) and fibrinolysis. (Fibrinolysis is the dissolution of fibrin by enzymes; fibrin is an insoluble protein that is essential to clotting of blood, formed from fibrinogen by action of thrombin; thrombin is an enzyme resulting from activation of prothrombin, which helps the conversion of fibrinogen to fibrin). The breaking apart of the matrix and fibrinolysis is controlled and balanced by stimulators and inhibitors of the plasminogen activation system. The full article gives an overview of these processes during tumor progression. It shows a new and unusual way to inhibit angiogenesis by removal of the matrix. This is done through specific and localized overstimulation of the plasminogen activation system.
EUROPEAN JOURNAL OF CANCER, 2000, Vol 36, Iss 13, pp 1695-1705
15. Anti-angiogenic agents and therapies in development
Development of therapies aimed at inhibiting the growth of new blood vessels (angiogenesis) is among the most intensively studied approaches to the treatment of cancer. Deciphering the many biological processes involved in tumor angiogenesis has led to the development of new drugs targeting angiogenic growth factors. More than 35 anti-angiogenic drugs have already entered clinical trials in cancer patients and most of them are reviewed in the full article. The results of these studies show that the common steps used worldwide in developing new anticancer agents could be inappropriate to assess the efficacy of drugs that do not target cancer cells directly. One of the major challenges for clinical researchers is to define new parameters adapted to anti-angiogenic drugs when designing clinical trials. Once this has been achieved, the successful anti-angiogenic drugs will need to be further refined in order to determine where they best fit in our current medicines, and surgical procedures, either as single drugs or in combination with classical anticancer therapies. The use of these new drugs in the future encompasses every aspect of cancer management, not only from relief to curative treatment, but also in the prevention of cancer.
EUROPEAN JOURNAL OF CANCER, 2000, Vol 36, Iss 13, pp 1713-1724
16. Effects of growth hormone treatment in obese men
Abdominal obesity is associated with blunted growth hormone (GH) secretion and an unfavorable lipoprotein pattern. A study determined the effect of GH treatment (9.5 mu g/kg/day) on low-density lipoprotein (LDL) size and on blood lipoprotein concentrations in 30 abdominally obese men (aged 48-66) for nine months. Results showed blood concentrations of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) were reduced. Blood lipoprotein(a) [Lp(a)] concentration increased. Average low-density lipoprotein (LDL) particle diameter was marginally increased by active treatment as compared with placebo. There were no changes in the blood concentrations of high-density lipoprotein-cholesterol (HDL-C). Thus, GH treatment in abdominally obese men beneficially reduced blood level concentrations of TC, LDL-C and apoB, and marginally increased average LDL diameter, while blood Lp(a) increased.
GROWTH HORMONE & IGF RESEARCH, 2000, Vol 10, Iss 3, pp 118-126
17. Phytosterols as anticancer components
Phytosterols (PS) or plant sterols are structurally similar to cholesterol. The most common PS are p-sitosterol, campesterol and stigmasterol. Studies suggest that dietary PS may offer protection from the most common cancers in Western societies, such as colon, breast and prostate cancer. The full article summarizes the findings of these studies and the possible mechanisms by which PS offer this protection. These include the effect of PS on membrane structure and function of tumor and host tissue, signal transduction pathways that regulate tumor growth and cell death, immune function and cholesterol metabolism. Suggestions for future studies to fill the gaps in our knowledge have been given.
JOURNAL OF NUTRITION, 2000, Vol 130, Iss 9, pp 2127-2130
Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. In westernized societies, it is the underlying cause of about 50% of all deaths. Studies have revealed several important environmental and genetic risk factors associated with atherosclerosis. Progress in defining the cellular and molecular interactions involved, however, has been hindered by the disease's complexity. Over the past decade, the availability of new investigative tools, including genetically modified mouse models of disease, has resulted in a clearer understanding of the molecular mechanisms that connect altered cholesterol metabolism and other risk factors to the development of atherosclerotic plaque. It is now clear that atherosclerosis is not simply an inevitable degenerative consequence of aging, but rather a chronic inflammatory condition that can be converted into an acute clinical event by the rupturing of plaque, and thrombosis (blood clot).
NATURE, 2000, Vol 407, Iss 6801, pp 233-241
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