Whole Body Health Sale

ANTIOXIDANTS



Table of Contents
image Rationales for micronutrient supplementation in diabetes
image Contraction and relaxation of aortas from diabetic rats: effects of chronic anti-oxidant and aminoguanidine treatments.
image Antioxidant vitamins in hospitalized elderly patients: Analysed dietary intakes and biochemical status
image Antioxidant depletion, lipid peroxidation, and impairment of calcium transport induced by air-blast overpressure in rat lungs
image The use of antioxidants in healing
image Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E, and the carotenoids.
image Dietary intake and plasma levels of antioxidant vitamins in health and disease: A hospital-based case-control study
image Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction
image Antioxidant therapy using high dose vitamin C: Reduction of postburn resuscitation fluid volume requirements
image Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise
image Modification of the daily photoreceptor membrane shedding response in vitro by antioxidants
image Tirilazad mesylate protects vitamins C and E in brain ischemia-reperfusion injury
image Biochemical basis of ozone toxicity
image Decreases in tissue levels of ubiquinol-9 and -10, ascorbate and alpha-tocopherol following spinal cord impact trauma in rats
image An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes
image Antioxidants, fat and skin cancer
image Photoprotective effect of superoxide scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse
image Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation
image Diminished production of malondialdehyde after carotid artery surgery as a result of vitamin administration
image Spermine partially normalizes in vivo antioxidant defense potential in certain brain regions in transiently hypoperfused rat brain
image Positron-labeled antioxidant 6-deoxy-6-(18F)fluoro-L-ascorbic acid: Increased uptake in transient global ischemic rat brain
image Maternal infusion of antioxidants (Trolox and ascorbic acid) protects the fetal heart in rabbit fetal hypoxia
image Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study
image Antioxidant vitamins and disease - Risks of a suboptimal supply
image Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: An epidemiological update with special attention to carotene and vitamin C
image Oxidative protein damage in human diabetic eye: evidnal participation.
image Abnormalities in diabetes or experimental galactosemia. IV. Antioxidant defense system.
image Nutritional antioxidants, red cell membrane fluidity and blood viscosity in type 1 (insulin dependent) diabetes mellitus.
image [Prospective biochemical study of the antioxidant defense capacity in retinopathy of premokemiai vizsgalata retinopathia preamaturorumban.
image [Antioxidants for prophylaxis of eye diseases]
image [Erythrocyte and plasma antioxidant activity in diabetes mellitus type I]
image Oxidative protein damage in human diabetic eye: Evidence of a retinal participation
image Abnormalities of retinal metabolism in diabetes or experimental galactosemia. III. Effects of antioxidants
image Oxidative stress and diabetic vascular complications
image Pharmacological prevention of diabetic microangiopathy
image Erythrocyte and plasma antioxidant activity in type I diabetes mellitus
image Status of antioxidants in patients with diabetes mellitus with and without late complications
image Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.
image Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury.
image Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson's disease.
image [The dose-dependent effects of a combination of different classes of antioxidants exemplified by dibunol and beta-carotene]
image Oxidative damage and defense.
image The effect of dietary fat, antioxidants, and pro-oxidants on blood lipids, lipoproteins, and atherosclerosis.
image Reliability of a food frequency questionnaire to assess dietary antioxidant intake.
image Dietary antioxidants and Parkinson disease. The Rotterdam Study.
image Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control study. The ARIC Study Investigators. Atherosclerosis Risk in Communities.
image Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study.
image [Prevalence and risk factors in the population of Graz (Austrian Stroke Prevention Study)]
image Beta-2-agonists have antioxidant function in vitro. 2. The effect of beta-2-agonists on oxidant-mediated cytotoxicity and on superoxide anion generated by human polymorphonuclear leukocytes.
image Antioxidants in the prevention of atherosclerosis.
image Bronchial reactivity and dietary antioxidants.
image Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol.
image [Alcohol and free radicals: from basic research to clinical prospects]
image Oxidized low-density lipoprotein and atherosclerosis.
image Serum levels of antioxidant vitamins in relation to coronary artery disease: a case control study of Koreans.
image Antioxidants in food and chronic degenerative diseases.
image Randomized trials of dietary antioxidants in cardiovascular disease prevention and treatment.
image Basic research in antioxidant inhibition of steps in atherogenesis.
image Oxidative susceptibility of low-density lipoproteins--influence of regular alcohol use.
image Do hydroxy-carotenoids prevent coronary heart disease? A comparison between Belfast and Toulouse.
image Antioxidants in cardiovascular disease: randomized trials.
image Randomized trial of antioxidants in the primary prevention of Alzheimer disease warranted?
image Lipid peroxidation and antioxidant vitamins C and E in hypertensive patients.
image Update on dietary antioxidants and cancer.
image Antioxidants in health and disease
image Multicenter ophthalmic and nutritional age-related macular degeneration study--part 2: antioxidant intervention and conclusions.
image Multicenter ophthalmic and nutritional age-related macular degeneration study--part 1: design, subjects and procedures.
image Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?
image The role of oxidized lipoproteins in atherogenesis.
image [Bronchopulmonary dysplasia]
image Oxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model.
image [The significance of oxidized low density lipoprotein in atherosclerosis]
image In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation.
image Antioxidants and age-related eye disease. Current and future perspectives.
image [Free radicals in the central nervous system]
image Protection by multiple antioxidants against lipid peroxidation in rat liver homogenate.
image Inhibition of Ca2+-pump ATPase and the Na+/K+-pump ATPase by iron-generated free radicals. Protection by 6,7-dimethyl-2,4-DI-1-pyrrolidinyl-7H-pyrrolo[2,3-d] pyrimidine sulfate (U-89843D), a potent, novel, antioxidant/free radical scavenger.
image Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women
image Oxidative stress and antioxidant therapy in Parkinson's disease
image In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia.
image Antioxidant mechanism and protection of nigral neurons against MPP+ toxicity by deprenyl (selegiline)
image Parkinson's disease: a chronic, low-grade antioxidant deficiency?
image Free radicals in brain metabolism and pathology.
image Free radicals and their scavengers in Parkinson's disease.
image Role of dietary lipid and antioxidants in bone metabolism
image [Preventive treatment of diabetic microangiopathy: blocking the pathogenic mechanisms]
image COSMETICS -- Marketing
image Measurement of low-molecular-weight antioxidants, uric acid, tyrosine and tryptophan in plaques and white matter from patients with multiple sclerosis.
image On the causes of multiple sclerosis
image Alpha-tocopherol and hydroperoxide content in breast adipose tissue from patients with breast tumors.
image Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York, United States)
image Extraocular, limb and diaphragm muscle group-specific antioxidant enzyme activity patterns in control and mdx mice.
image Free radicals, lipid peroxides and antioxidants in blood of patients ith myotonic dystrophy.
image Antioxidants and angiogenetic factor associated with age-related macular degeneration (exudative type)
image Studies on the mechanism of early onset macular degeneration in c ynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress
image Association of zinc and antioxidant nutrients with age-related maculopathy.
image Antioxidant enzymes of the human retina: Effect of age on enzyme activity of macula and periphery
image Antioxidant enzymes in RBCs as a biological index of age related macular degeneration
image Antioxidant defenses in metal-induced liver damage
image Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage.
image The role of antioxidants in the prevention of cardiovascular diseases
image Essential antioxidants in cardiovascular diseases--lessons for Europe
image Antioxidant vitamin intake and coronary mortality in a longitudinal population study.
image Can anti-oxidants prevent ischaemic heart disease?
image Antioxidant therapy in the aging process.
image Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects.
image Micronutrient profiles in HIV-1-infected heterosexual adults
image Antioxidant-micronutrients and HIV infection
image Can antioxidants prevent ischemic heart disease?
image Antioxidant therapy in the aging process.
image Acute phase response and plasma carotenoid concentrations in older women: Findings from the nun study.
image Endothelial dysfunction: Clinical implications.
image Use of antioxidant vitamins in the cardiovascular disease. A review of epidemiological study and clinical trials.
image The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes.
image Smoking, plasma antioxidants and essential fatty acids before and after nutratherapy.
image Reduction of plasma peroxide levels by oral antioxidants.
image Systemic oxidative stress in asthma, COPD, and smokers
image Role of oxidants/antioxidants in smoking-induced lung diseases
image Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus
image Spice constituents scavenging free radicals and inhibiting pentosidine formation in a model system.
image Potential therapeutic approaches to the treatment or prevention of diabetic neuropathy: evidence from experimental studies.
image Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3
image Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine
image Nutritional antioxidants and the modulation of inflammation: theory and practice.
image Antioxidant vitamins in cataract prevention.
image Free radical tissue damage: protective role of antioxidant nutrients.
image Free radical tissue damage: protective role of antioxidant nutrients.
image [Antioxidative vitamins and cataracts in the elderly]
image Prevention of cataracts by nutritional and metabolic antioxidants.
image Free radicals, exercise, and antioxidant supplementation
image Fibronectin fragment mediated cartilage chondrolysis. I. Suppression by anti-oxidants
image Overview of conditioning related life-threatening toxicities of marrow transplantation
image [Cardioprotection in chemo- and radiotherapy for malignant diseases--an echocardiographic pilot study]
image Place of antioxidants in active photoprotection
image Indicators of free radical activity in patients developing radiation pneumonitis
image The effect of antioxidants on bleomycin treatment in in vitro and in vivo genotoxicity assays
image Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus.
image Free radical tissue damages in the anterior segment of the eye in experimental autoimmune uveitis
image Intervention at diagnosis of type I diabetes using either antioxidants or photopheresis
image Free radical theory of aging: Beneficial effect of antioxidants on the life span of male NZB mice: Role of free radical reactions in the deterioration of the immune system with age and in the pathogenesis of systemic lupus erythematosus
image Reduced superoxide dismutase in lung cells of patients with asthma
image Antioxidant protection against adrenaline-induced arrhythmias in rats with chronic heart hypertrophy.
image The effects of antioxidants on reperfusion dysrhythmias
image [Essential antioxidants in cardiovascular diseases--lessons for Europe]
image Muscle ubiquinone and plasma antioxidants in effort angina
image Effect of antioxidants on postoperative hyperamylasemia in coronary bypass surgery
image Antioxidant depletion during aortic aneurysm repair
image Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting
image Evaluation of antioxidants, protein, and lipid oxidation products in blood from sporadic amiotrophic lateral sclerosis patients.
image Antioxidants in peripheral nerve.
image Free Radicals and Neuroprotection
image Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases.
image Experience over 17 years with antioxidant treatment in Spielmeyer-Sjogren disease.
image Antioxidant of the coronary diet and disease
image Enhanced capacity of n-3 fatty acid-enriched macrophages to oxidize low density lipoprotein mechanisms and effects of antioxidant vitamins
image The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein
image Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men
image Animal studies on antioxidants
image Abnormal antioxidant vitamin and carotenoid status in chronic renal failure
image Antioxidants in cardiovascular disease: Randomized trials
image Dietary antioxidants and cognitive function in a population-based sample of older persons: The Rotterdam study
image Oxidized low density lipoproteins in atherogenesis: Role of dietary modification
image Antioxydant vitamins and risk of cardiovascular diseases
image The significance of oxidised low-density lipoprotein in atherosclerosis
image Prevention of atherosclerosis with dietary antioxidants: Fact or fiction?
image Randomized, controlled trial of antioxidant vitamins and cardioprotective diet on hyperlipidemia, oxidative stress, and development of experimental atherosclerosis: The diet and antioxidant trial on atherosclerosis (DATA)
image Optimal diet for reducing the risk of arteriosclerosis
image Prevention of atherosclerosis: The potential role of antioxidants
image Advanced glycation endproducts in ageing and Alzheimer's disease
image Molecular basis of Alzheimer's disease.
image New therapeutic approaches to Alzheimer's disease.
image A pilot study of blood antioxidant and free radical marker profiles in patients awaiting coronary artery bypass grafting
image Oxygen free radical-induced histamine release during intestinal ischemia and reperfusion
image Antioxidant drugs block in vitro the neurotoxicity of CSF from atients with amyotrophic lateral sclerosis
image The role of antioxidant agents on experimental ulcerative colitis
image Rutoside as mucosal protective in acetic acid-induced rat colitis
image Inhibitory effect of a traditional Chinese medicine, Juzen-taiho-to, on progressive growth of weakly malignant clone cells derived from murine fibrosarcoma.

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Multicenter ophthalmic and nutritional age-related macular degeneration study--part 2: antioxidant intervention and conclusions.

Richer S

Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064, USA.

J Am Optom Assoc (UNITED STATES) Jan 1996, 67 (1) p30-49

BACKGROUND: The experimental design, subjects, procedures and baseline data for the prospective double blind dry ARMD-antioxidant intstudy have bee n described in Part 1. METHODS: At eight DVA medical centers, 32 patients (group one) were assigned a placebo and 39 patients (group two) a "broad spectrum" antioxidant capsule. Data was collected in five areas: demographic; ophthalmic; dietary analysis of daily food intake; serum analysis; and adverse gastrointestinal symptoms. Data was serially acquired at baseline, 6 months, 12 months and 18 months, and was analyzed by univariate repeated factors ANOVA, p = 0.05. RESULTS: Group two (antioxidant po BID) maintained their distance LogMAR visual acuity (p = 0.03), while there was a trend toward both stabilized near M print (p = 0.07) and 6 cycle/degree contrast sensitivity (p approximately 0.10), in left eyes. However, group two (antioxidant) also had increased cortical opacification of the right lens (p = 0.04), compared to group one (placebo). Self perceived stabilization of vision was reported by subjects in group two and supported the objective data (Pearson chi square; p = 0.05). CONCLUSIONS: A specific 14 component antioxidant capsule taken twice daily stabilized but did not improve dry ARMD over the study period of 1.5 years. The ARMD stabilized eyes had less advanced disease functionally but not by fundus appearance. Decreased intake of cardioprotective nutrients (vitamin E, zinc, magnesium, B6 and folate) in ARMD patients remained constant over the course of the trial.



Multicenter ophthalmic and nutritional age-related macular degeneration study--part 1: design, subjects and procedures.

Richer S

Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064, USA.

J Am Optom Assoc (UNITED STATES) Jan 1996, 67 (1) p12-29

BACKGROUND: A prospective 18 month, double-blind case-controlled study was designed to determine whether a specific over-the-counter multivitamin/mineral/antioxidant nutrient capsule taken twice daily prevents the progression of, or improves the outcome of non-exudative ARMD. Two randomly assigned experimental ARMD groups are compared to each other, to age matched ARMD-free case controls and to 1994 NHANES III nutritional data. METHODS: Th assigned to group one (placebo) and 39 dry ARMD patients were assigned to group two (Ocuguard, a broad spectrum antioxidant capsule). A third age and sex matched ARMD-free case control group of 13 patients who met the same entrance criteria were also selected. All participants underwent thorough visual and nutritional evaluation prior to initiation of the study. Both ophthalmic tests and dietetic assessments were also performed at 6, 12 and 18 months following a 2-week initiation period. RESULTS: In comparison to NHANES-III age stratified population data and the Recommended Daily Allowance (but not case controls), the ARMD population manifested decreased intake of nutrients vital to cardiovascular health: vitamin E, magnesium, zinc, vitamin B6 and folic acid. The two randomly assigned experimental groups were well matched, with little difference in baseline demographic, ocular, hematologic and pre-intervention symptoms. There were differences in nutritional intake between the two groups, due primarily to significantly higher percent ideal body weight in group two.



Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?

McAlindon TE; Jacques P; Zhang Y; Hannan MT; Aliabadi P; Weissman B; Rush D; Levy D; Felson DT

Arthritis Center, Boston University Medical Center, Massachusetts, 02118, USA.

Arthritis Rheum (UNITED STATES) Apr 1996, 39 (4) p648-56

OBJECTIVE: Cumulative damage to tissues, mediated by reactive oxygen species, has been implicated as a pathway that leads to many of the degenerative changes associated with aging. We hypothesized that increased intake of antioxidant micronutrients might be associated with decreased rates of osteoarthritis (OA) in the knees, a common age-related disorder. METHODS: Participants in the Framingham Osteoarthritis Cohort Study underwent knee evaluations by radiography at examinations 18 (1983-1985) and 22 (1992-1993). Usual dietary intake was assessed using the Food Frequency Questionnaire, administered at examination 20 (1988-1989). Knees without OA at baseline (Kellgren and Lawrence [K&L] grade < or = 1) were classified as having incident OA if they had a K&L grade > or = 2 at followup. Knees with OA at baseline were classified as having progressive OA if their score increased by > or = 1 at followup. Knees were also classified as having cartilage loss or osteophyte growth if their maximal joint space narrowing or osteophyte growth score increased by > or = 1 (range 0-3). The association of vitamin C, beta carotene, and vitamin E intake, ranked in sex-specific tertiles, with incidence and progression of OA was compared with that of a panel of nonantioxidant vitamins, Bl, B6, niacin, and folate, using logistic regression and generalized estimation equations to adjust for correlation between fellow knees. The lowest tertile for each dietary exposure was used as the referent category. Odds ratios (OR) were adjusted for age, sex, body mass index, weight change, knee injury, physical activity, energy intake, and health status. RESULTS: Six hundred forty participants received complete assessments. Incident and progressive OA occurred in 81 and 68 knees, respectively. We found no significant association of incident OA with any nutrient. A 3-fold reduction in risk of OA progression was found for both the middle tertile (adjusted OR = 0.3, 95% confidence interval [95% CI] 0.1-0.8) and highest tertile (adjusted OR = 0.3, 95% CI 0.1-0.6) of vitamin C intake. This related predominantly to a reduced risk of cartilage loss (adjusted OR = 0.3, 95% CI 0.1-0.8). Those with high vitamin C intake also had a reduced risk of developing knee pain (adjusted OR = 0.3, 95% CI 0.1-0.8). A reduction in risk of OA progression was seen for beta carotene (adjusted OR = 0.4, 95% CI 0.2-0.9) and vitamin E intake (adjusted OR = 0.7, 95% CI 0.3-1.6), but was less consistent. No significant associations were observed for the nonantioxidant nutrients. CONCLUSION: High intake of antioxidant micronutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with OA. We found no effecpreliminary findings warrant confirmation.



The role of oxidized lipoproteins in atherogenesis.

Berliner JA; Heinecke JW

Department of Pathology, University of California Los Angeles 90024, USA.

Free Radic Biol Med (UNITED STATES) 1996, 20 (5) p707-27

This article reviews our current understanding of the mechanisms of low-density lipoprotein (LDL) oxidation and the potential role of oxidized lipoproteins in atherosclerosis. Studies in hypercholesterolemic animal models indicate that oxidation of LDL is likely to play an important role in atherogenesis. Epidemiological investigations further suggest that the dietary intake of antioxidants is inversely associated with the risk of vascular disease, suggesting that oxidized LDL may be important in human atherosclerosis. By activating inflammatory events, oxidized lipoproteins may contribute to all stages of the atherosclerotic process. Lipoprotein oxidation is promoted by several different systems in vitro, including free and protein-bound metal ions, thiols, reactive oxygen intermediates, lipoxygenase, peroxynitrite, and myeloperoxidase. Intracellular proteins that bind iron or regulate iron metabolism might also play an important role. The physiologically relevant pathways have yet to be identified, however. We assess recent findings on the effects of antioxidants in vivo and suggest potential strategies for inhibiting oxidation in the vessel wall. (265 Refs.)



[Bronchopulmonary dysplasia]

Clement A

Service de Physiologie, Hopital Trousseau, Paris.

Rev Mal Respir (FRANCE) Jul 1996, 13 (3) p243-9

Bronchopulmonary dysplasia (BPD), a respiratory disorder first described in prematurely born infants with respiratory distress syndrome (RDS) treated with mechanical ventilation and oxygen supplementation, is the most common cause of chronic lung disease in infants. It is defined as the need for increased inspired oxygen at 28 days of age, and is observed with the highest frequency following premature delivery of very low birth weight infants. Indeed, an incidence of 48% has been recently reported in a population with a mean gestational age of 27 weeks. The etiology of BPD is multifactorial including lung immaturity, respiratory distress, oxygen therapy, and mechanical ventilation. Based on the current understanding of the pathogenesis of the disease, several therapeutical strategies are used. One of them is focused on the prevention of BPD by correcting surfactant deficiency in premature infants with RDS using exogenous surfactant, and also by improving the techniques of mechanical ventilation used for the management of RDS. Another approach which is being deveon the factors involved in the processes of repair of the injured immature lung. These factors include the use of inhibitors of the inflammatory cascade, antioxidants, and inhibitors of fibrosis. (42 Refs.)



Oxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model.

Prasad K; Gupta JB; Kalra J; Lee P; Mantha SV; Bharadwaj B

Department of Physiology, University of Saskatchewan, Saskatoon, Canada.

J Mol Cell Cardiol (ENGLAND) Feb 1996, 28 (2) p375-85

We investigated the effects of chronic volume overload in the absence or presence of vitamin E supplements on the cardiac function and contractility, cardiac malondialdehyde (MDA)--a lipid peroxidation product--cardiac antioxidant enzyme activity and antioxidant reserve in canine model. The dogs were divided into three groups of seven dogs each: group I, control; group II, mitral regurgitation (MR) of 4 months duration; and group III, MR of 4 months duration receiving vitamin E (40 U/kg/daily) orally. MR was created by detaching two or more chordae tendinae to raise left atrial pressure to 2.5 to three times normal. MR produced a decrease in the index of myocardial contractility with little change in myocardial function. Decrease in myocardial (left and right ventricles) contractility was associated with an increase in cardiac MDA, and a decrease in cardiac antioxidant reserve and antioxidant enzyme activity. Prevention of volume overload-induced decrease in myocardial contractility by vitamin E was associated with a decrease in cardiac MDA and an increase in cardiac antioxidant reserve and glutathione peroxidase activity towards control levels. Superoxide dismutase and catalase activity remained depressed in vitamin E-treated group. The results indicate that chronic volume overload decreases the contractility of both right and left ventricles and is associated with oxidative stress in both ventricles. These results support the hypothesis that oxygen free radicals are involved in the chronic volume overload-induced cardiac depression.



[The significance of oxidized low density lipoprotein in atherosclerosis]

Hansen PR

Medicinsk afdeling B, Rigshospitalet, Kobenhavn.

Ugeskr Laeger (DENMARK) May 6 1996, 158 (19) p2706-10

The "oxidation hypothesis" states that oxidised low-density lipoprotein (ox-LDL) plays a central role in atherogenesis. LDL oxidation is a chaotic process initiated by reactive oxygen species. Enhanced uptake of ox-LDL in macrophages leads to foam cell formation in vitro, and ox-LDL has a variety of other experimental proatherogenic effects, e.g., endothelial cell activation, immunogenicity, platelet aggregation, and inhibition of endothelium-dependent vaso-relaxation. There are methodological limitations in the current laboratory methods aimed at characterization of the oxidative state of LDL. However, considerable evidence indicates that ox-LDL is found in plasma, arteries, and atheromatous plaques of humans, although the significance of this phenomenon is unknown. Antioxidants may inhibit atherosclerosis in experimental animals, and epidemiological data suggest an inverse relation between the intake of antioxidant vitamins and the risk of coronary artery disease. Randomised prospective trials are in progress, and until their conclusion, the clinical effect of antioxidant therapy in man remains unknown. (40 Refs.)



In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation.

Blackwell TS; Blackwell TR; Holden EP; Christman BW; Christman JW

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 27232, USA.

J Immunol (UNITED STATES) Aug 15 1996, 157 (4) p1630-7

We hypothesized that endotoxin injection in rats would stimulate in vivo nuclear factor-kappa B (NF-kappa B) activation in lung tissue and that antioxidant treatment before endotoxin injection would attenuate endotoxin-induced NF-kappa B activation, chemokine gene expression, and neutrophilic lung inflammation. We studied NF-kappa B activation in rat lung tissue following a single i.p. injection of endotoxin (6 mg/kg). After in vivo endotoxin treatment, lung NF-kappa B activation peaked at 2 h and temporall the expression of cytokine-induced neutrophil chemoattractant mRNA in lung tissue. Treatment with the antioxidant N-acetylcysteine (NAC) 1 h before endotoxin resulted in decreased lung NF-kappa B activation in a dose-dependent manner (from 200-1000 mg/kg) and diminished cytokine-induced neutrophil chemoattractant mRNA expression in lung tissue. Treatment with NAC significantly suppressed endotoxin-induced neutrophilic alveolitis. The average total lung lavage neutrophil count was 5.5 x 10(6) with endotoxin treatment vs 0.9 x 10(6) with NAC treatment before endotoxin. The NF-kappa B pathway represents an attractive therapeutic target for strategies to control neutrophilic inflammation and lung injury.



Antioxidants and age-related eye disease. Current and future perspectives.

Christen WG; Glynn RJ; Hennekens CH

Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Ann Epidemiol (UNITED STATES) Jan 1996, 6 (1) p60-6

Oxidative mechanisms may play an important role in the pathogenesis of age-related eye disease, in particular cataract and macular degeneration, the two most important causes of visual impairment in older adults. For this reason, there is considerable interest in determining whether vitamins and trace minerals with antioxidant properties can be of benefit in preventing the onset or progression of disabling eye disease. Basic research studies have shown that antioxidants can protect against the cumulative effects of oxidative stress in animal models of cataract and macular degeneration. Data from observational epidemiological studies in humans, however, are inconclusive. While results from several studies, primarily cross-sectional and case-control, are compatible with a possible protective role for micronutrients in disease development, data for specific nutrients or specific disease types have often been inconsistent. Further, these observational studies are limited because of the inherent imprecision of dietary exposure data and the likely effects of uncontrolled confounding. Thus, reliable data regarding a potentially important benefit of vitamin supplementation in eye disease will emerge mainly from well-designed, large-scale, randomized trials. (79 Refs.)



[Free radicals in the central nervous system]

Rokyta R; Racek J; Holecek V

Ustav fyziologie a klinicke fyziologie 3. lekarske fakulty UK, Praha.

Cesk Fysiol (CZECH REPUBLIC) Mar 1996, 45 (1) p4-12

Central nervous system has a low antioxidative capacity, which is formed mainly by ascorbic acid. Therefore the cerebral tissue is threatened by the increased formation of free radicals and their metabolites (ROS--reactive oxygen species). ROS are formed such as in reperfusion phase after ischemia and in catecholamine metabolism, in oxidative stress due to hyperglycaemia. Polyunsaturated fatty acids (PUFA) are peroxidased by ROS; proteins and DNK are damaged as well. Free radicals are involved in etiology and pathogenesis of many CNS diseases, such as neuritis, Alzheimer disease, Parkinson disease, Huntington disease, aging and atherosclerosis of the brain, epilepsy, etc. During the antioxidant therapy it is necessary to consider the types of ROS, their origin and their mode of action, whether to administer hydrophilic or lipophilic antioxidants, eventually chelate agents, etc. Hydrophylic antioxidants are acting very soon after the administration, whereas the lipophilic ones reach their target tissues with a great delay. Therefore it is better to apply them preferentially like a prevention, if possible. Enzymatic antioxidants (SOD, GSPHx and catalase and others) are usually acting only for a short time. The methods of estimation of free radicals attacks are discussed as well their possible pathophysiological effects. (34 Refs.)



Protection by multiple antioxidants against lipid peroxidation in rat liver homogenate.

Chen H; Tappel A

Department of Pharmacology, School of Medicine, University of Washington, Seattle, USA.

Lipids (UNITED STATES) Jan 1996, 31 (1) p47-50

The purpose of this study was to test the hypothesis that multiple antioxygenic nutrients provide increased protection against lipid peroxidative damage to rat liver. Rats were fed diets (i) deficient in vitamin E and selenium (Diet 1), (ii) supplemented with vitamin E and selenium (Diet 2), (iii) supplemented with (ii) and in addition trolox C, N-acetylcysteine, coenzyme Q0, and (+)-catechin (Diet 3), or (iv) supplemented with (iii) and in addition beta-carotene, ascorbic acid palmitate, canthaxanthin, and coenzyme Q10 (Diet 4). Liver homogenates were obtained from three rats fed each of the diets for six weeks and were incubated at 37 degrees C up to two hours with and without exogenous tertiary-butyl hydroperoxide (TBHP) or Cu2+. Lipid peroxidation was determined by measurement of thiobarbituric acid substances. Diets 2 and 3 significantly protected against in vivo hepatic lipid peroxidation, and this protection was augmented by Diet 4. Diets 2, 3, and 4 were protective against mild oxidation induced by TBHP or Cu2+. During incubations with exogenous TBHP and Cu2+, there were only small differences between diets supplemented with antioxidants in inhibition of lipid peroxidation, indicating that diets supplemented with vitamin E and selenium (Diet 2) may have provided the maximal protection for liver. The possible mechanisms of protection provided by multiple antioxidants in diets were discussed. Protection by multiple antioxidants against lipid peroxidation may translate to prevention of peroxidative damage to human tissue, a factor in human disease.



Inhibition of Ca2+-pump ATPase and the Na+/K+-pump ATPase by iron-generated free radicals. Protection by 6,7-dimethyl-2,4-DI-1-pyrrolidinyl-7H-pyrrolo[2,3-d] pyrimidine sulfate (U-89843D), a potent, novel, antioxidant/free radical scavenger.

Rohn TT; Hinds TR; Vincenzi FF

Department of Pharmacology, University of Washington, Seattle 98195, USA.

Biochem Pharmacol (ENGLAND) Feb 23 1996, 51 (4) p471-6

Preincubation of red blood cell (RBC) membranes with a model system known to generate reactive oxygen species (ROS) and free radicals (200 microM ferrous sulfate and 200 microM EDTA, Fe2+/EDTA) resulted inhibition of the Na+/K+ -pump ATPases was also associated with membrane protein crosslinking and lipid peroxidation, the latter as monitored by the formation of thiobarbituric acid reactive substances (TBARS). Inhibition of the ion transport ATPases, protein cross-linking and formation of TBARS were prevented by U-89843D in a concentration-dependent manner, with half-maximal protection seen at 0.3 microM. U-89843D was more potent than the classical antioxidant butylated hydroxytoluene. Neither U-89843D nor the solvent DMSO had any effect on the assay of TBARS. U-89843D exerted only minimal inhibitory activity on ATPase activities. Thus, U-89843D was potent in vitro in preventing a variety of membrane-damaging reactions mediated by ROS. It is suggested that protection of membranes from ROS-mediated damage is of potential usefulness in the prevention and treatment of certain disease processes.



Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women

Kushi LH; Folsom AR; Prineas RJ; Mink PJ; Wu Y; Bostick RM

Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis 55454-1015, USA.

N Engl J Med (UNITED STATES) May 2 1996, 334 (18) p1156-62

BACKGROUND: The role of dietary antioxidant vitamins in preventing coronary heart disease has aroused considerable interest because of the knowledge that oxidative modification of low-density lipoprotein may promote atherosclerosis. METHODS. We studied 34,486 postmenopausal women with no cardiovascular disease who in early 1986 completed a questionnaire that assessed, among other factors, their intake of vitamins A, E, and C from food sources and supplements. During approximately seven years of follow-up (ending December 31, 1992), 242 of the women died of coronary heart disease. RESULTS. In analyses adjusted for age and dietary energy intake, vitamin E consumption appeared to be inversely associated with the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21,809 women who did not consume vitamin supplements (relative risks from lowest to highest quintile of vitamin E intake, 1.0, 0.68, 0.71, 0.42, and 0.42; P for trend 0.008). After adjustment for possible confounding variables, this inverse association remained (relative risks from lowest to highest quintile, 1.0, 0.70, 0.76, 0.32, and 0.38; P for trend, 0.004). There was little evidence that the intake of vitamin E from supplements was associated with a decreased risk of death from coronary heart disease, but the effects of high-dose supplementation and the duration of supplement use could not be definitely addressed. Intake of vitamins A and C did not appear to be associated with the risk of death form coronary heart disease. CONCLUSIONS. These results suggest that in postmenopausal women the intake of vitamin E from food is inversely associated with the risk of death from coronary heart disease and that such women can lower their risk without using vitamin supplements. By contrast, the intake of vitamins A and C was not associated with lower risks of dying from coronary disease.



Oxidative stress and antioxidant therapy in Parkinson's disease

Progress in Neurobiology (United Kingdom), 1996, 48/1 (1-19)

Parkinson's disease, known also as striatal dopamine deficiency syndrome, is a degenerative disorder of the central nervous system characterized by akinesia, muscular rigidity, tremor at rest, and postural abnormalities. In early stages of parkinsonism, there appears to be a compensatory increase in the number of dopamine receptors to accommodate the initial loss of dopamine neurons. As the disease progresses, the number of dopamine receptors decreases, apparently due to the concomitant degeneration of dopamine target sites on striatal neurons. The loss of dopaminergic neurons in Parkinson's disease results in enhanced metabolism of dopamine, augmenting the formation of H2O2, thus leading to generation of highly neurotoxic hydroxyl radicals (OH.). The generation of free radicals can also be produced by 6-hydroxydopamine or MPTP which destroys striatal dopaminergic neurons causing parkinsonism in experimental animals as well as human beings. Studies of the substantia nigra after death in Parkinson's disease have suggested the presence of oxidative stress and depletion of reduced glutathione; a high level of total iron with reduced level of ferritin; and deficiency of mitochondrial complex I. New approaches designed to attenuate the effects of oxidative stress and to provide neuroprotection of striatal dopaminergic neurons in Parkinson's disease include blocking dopamine transporter by mazindol, blocking NMDA receptors by dizocilpine maleate, enhancing the survival of neurons by giving brain-derived neurotrophic factors, providing antioxidants such as vitamin E, or inhibiting monoamine oxidase B (MAO-B) by selegiline. Among all of these experimental therapeutic refinements, the use of selegiline has been most successful in that it has been shown that selegiline may have a neurotrophic factor-like action rescuing striatal neurons and prolonging the survival of patients with Parkinson's disease.



In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia.

Ann N Y Acad Sci. 1994 Nov 17. 738P 25-36

The in vivo generation of .OH free radicals in specific brain regions can be measured by intracerebral microdialysis perfusion of salicylate, avoiding many of the pitfalls inherent in systemic administration of salicylate. Direct infusion of salicylate into the brain can minimize the hepatic hydroxylation of salicylate and its contribution to brain levels of 2,5-DHBA. Levels of 2,5-DHBA detected in the brain dialysate may reflect the .OH adduct plus some enzymatic hydroxylation of salicylate in the brain. After minimizing the contribution of enzyme and/or blood-borne 2,5-DHBA, the present data demonstrate the validity of the use of 2,3-DHBA and apparently 2,5-DHBA as indices of .OH formation in the brain. Therefore, intracranial microdialysis of salicylic acid and measurement of 2,3-DHBA appears to be a useful .OH trapping procedure for monitoring the time course of .OH generation in the extracellular fluid of the brain. These results indicate that nonenzymatic and/or enzymatic oxidation of the dopamine released by MPTP analogues in the extracellular fluid may play a key role in the generation of .OH free radicals in the iron-rich basal ganglia. Moreover, a site-specific generation of cytotoxic .OH free radicals and quinone/semiquinone radicals in the striatum may cause the observed lipid peroxidation, calcium overload, and retrograde degeneration of nigrostriatal neurons. This free-radical-induced nigral injury can be suppressed by antioxidants (i.e., U-78517F, DMSO, and deprenyl) and possibly hypothermia as well. In the future, this in vivo detection of .OH generation may be useful in answering some of the fundamental questions concerning the relevance of oxidants and antioxidants in neurodegenerative disorders during aging. It could also pave the way for the research and development of novel neuroprotective antioxidants and strategies for the early or preventive treatment of neurodegenerative disorders, such as Parkinson's disease (Wu et al., this issue), amyotrophic lateral sclerosis, head trauma, and possibly Alzheimer's cognitive dysfunction as well. In conclusion, this in vivo free-radical trapping procedure provides evidence to support a current working hypothesis that a site-specific formation of cytotoxic .OH free radicals in the basal ganglia may be one of the neurotoxic mechanisms underlying nigrostriatal degeneration and Parkinsonism caused by the dopaminergic neurotoxin MPTP. Addendum added in proof: The controversy concerning possible neurotoxic and/or neuroprotective roles of NO. in cell cultures was discussed and debated at the symposium (Wink et al., this issue; Dawson et al., this issue; Lipton et al., this issue).



Antioxidant mechanism and protection of nigral neurons against MPP+ toxicity by deprenyl (selegiline)

Ann N Y Acad Sci. 1994 Nov 17. 738P 214-21

The current research has demonstrated that MPP+ can induce lipid peroxidation in the nigrostriatal system of rat in vivo. Antioxidant agent U-78517F and .OH scavenger DMSO may protect against MPP+ toxicity through the inhibition of .OH radical-mediated oxidative injury in the substantia nigra. These findings indicate that the cytotoxic hydroxyl radical generated from dopamine oxidation in the iron-rich basal ganglia may contribute to the mechanism underlying the selective A9 melanized nigral degeneration in MPTP-Parkinsonism and possibly in idiopathic Parkinson's disease. In addition, the present studies also clearly demonstrate that deprenyl can substantially protect dopaminergic neurons against MPP+ toxicity in the substantia nigra zona compacta in vivo. The neuroprotective effect provided by deprenyl may not be the consequence of its inhibition of MAO-B activity or prevention of the uptake of MPP+ by dopaminergic neurons. A unique antioxidant property of deprenyl by suppressing .OH formation and associated oxidative injury induced by MPP+ may contribute to the apparent neuroprotective action. In perspective, this putative antioxidant effect of deprenyl may provide another mechanism to its overt neuroprotective effects against oxygen radical-mediated oxidative injury in some neurotoxic chemicals, such as 6-OHDA and DSP-4, and probably in Alzheimer's disease and senescent changes. Finally, based on the present data, a possible neuroprotective therapeutic window of deprenyl in the treatment of early Parkinson's disease has been proposed. It is suggested that deprenyl should be introduced as early as possible in de novo Parkinsonian patients to achieve its full neuroprotective effect on nigral degeneration. Moreover, a combination of early detection of individuals at risk of developing Parkinson's disease and early intervention of deprenyl and/or other centrally active antioxidants to these patients may provide a new preventive therapeutic strategy in the future, in addition to the current conventional levodopa treatment of Parkinson's disease.



Parkinson's disease: a chronic, low-grade antioxidant deficiency?

Med Hypotheses. 1994 Aug. 43(2). P 111-4

The cause of Parkinson's disease (PD) is aggressively being pursued. Several hypotheses have been advanced, yet none of these completely explains the large body of evidence research has already uncovered. A new hypothesis, that PD is caused by a chronic antioxidant deficiency state, is outlined in this article. Oxidative stress, mitochondrial abnormalities, epidemiology, genetics, toxins, history of PD and diet are discussed.



Free radicals in brain metabolism and pathology.

Br Med Bull. 1993 Jul. 49(3). P 577-87

Reactive oxygen metabolites (ROM), namely superoxide and hydroxyl free radicals and hydrogen peroxide, are produced as a consequence of the physiological metabolic reactions and functioning of the central nervous system. ROM have also been implicated in the aetiopathogenic processes of a number of pathological conditions of the brain. While primarily indirect, evidence for this view is accumulating, and credence for the participation of free radical oxidative interactions in promoting tissue injury in such conditions as brain trauma, ischaemia, and toxicity, and in neurodegenerative diseases such as Parkinson's disease, Alzheimer's dementia, multiple sclerosis, and lipofuscinosis, is growing. Concomitant with this new understanding of the injurious role of free radical oxidants in neural pathology, is the increasing appreciation for the need for both fundamental and clinical research into the development of the potential preventative and therapeutic benefits that are now being foreseen for a variety of antioxidant nutritional and pharmacological interventions.



Free radicals and their scavengers in Parkinson's disease.

Eur Neurol. 1993. 33 Suppl 1P 60-8

In recent years, it has been shown that active oxygen species or free radicals are closely involved in various diseases. Accumulating information supports the hypothesis that oxidative stress involving lipid peroxidation may contribute to the pathogenesis of Parkinson's disease. The objectives of this review are, first, to discuss some of the roles of active oxygen species in the pathogenesis of Parkinson's disease; second, to examine the possible effects of antioxidants as the protective therapy for Parkinson's disease, and, third, to summarize results from in vitro experiments that the dopamine agonist bromocriptine, used for treatment of Parkinson's disease, has a strong antioxidative effect.



Role of dietary lipid and antioxidants in bone metabolism

Nutrition Research (USA), 1997, 17/7 (1209-1228)

Recent investigations and clinical studies suggest that dietary lipids and antioxidant nutrients influence bone formation and cartilage biology. In animals, bone modeling appears to be optimal when (n-3) fatty acids are supplied in thediet to moderate the metabolic and physiologic effects of (n- 6) fatty acids. In osteoporosis, greater osteoclastic activity results in excessive mineral loss and bone destruction.New evidence supports the idea that dietary fatty acids and antioxidants can attenuate osteoclastic activity to reduce the severity of osteolytic diseases of the bone and joint. Moreover,(n-6) fatty acids may aggravate the deficiency of antioxidant enzyme protective systems in epiphyseal cartilage of long bones. For example, vitamin E was reported to increase in vivo trabecular bone formation rate and to restore collagen synthesis in chondrocytes enriched with linoleic acid. This review presents new information that documents a role for dietary lipids and antioxidants in supporting bone formation and cartilage function for optimal health.



[Preventive treatment of diabetic microangiopathy: blocking the pathogenic mechanisms]

Diabete Metab (FRANCE) 1994, 20 (2 Pt 2) p219-28

The development of drugs in order to block metabolic pathway of glucose responsible for diabetic vascular dysfunction is in progress. Aldose reductase inhibitors prevent or reduce the different components of vascular dysfunction, cataract, neuropathy and nephropathy in animal models of diabetes. Promising results have been observed in diabetic patients concerning the prevention of neuropathy and of retinopathy. Larger scale studies with the second generation compounds are in progress. Glycation inhibitors, mainly aminoguanidine, have been shown to prevent or reduce vascular dysfunction and microvascular complications in animal models. Trials in diabetic patients with aminoguanidine are just beginning. Anti-oxidant therapy is also at its early stage of development (vitamin E, vitamin C, alpha lipoic acid). Antiplatelet agents (aspirin, ticlopidine) have been demonstrated to reduce the progression of non proliferative diabetic retinopathy. Angiotensin converting enzyme inhibitors are of particular interest in preventing diabetic glomerulopathy.



COSMETICS -- Marketing

Environmental Nutrition, Mar96, Vol. 19 Issue 3, p1, 2p

Gives information on two probably three cosmetic companies that promises improved nutritional supplements. Names of cosmetic companies; What supplements promise to improve; Information on preliminary research on antioxidants and damaging effects of free radicals; Possible products for improving wrinkle skin, brittle nails and hair; EN's recommendations.

(no abstract)



Measurement of low-molecular-weight antioxidants, uric acid, tyrosine and tryptophan in plaques and white matter from patients with multiple sclerosis.

Eur Neurol (SWITZERLAND) 1992, 32 (5) p248-52

The levels of the antioxidants ascorbic acid, cysteine, reduced glutathione and alpha-tocopherol, of the free-radical marker uric acid and of the amino acids tyrosine and tryptophan were measured by means of high-pressure liquid chromatography in plaques, adjacent white matter and distant white matter from patients with multiple sclerosis, and in central nervous system tissue from patients without neurological diseases. Cholesterol and DNA were also determined, to check demyelination and cellularity. Uric acid was increased and glutathione correspondingly decreased in plaques; alpha-tocopherol was lowest in plaques and highest in distant white matter in all cases. Ascorbic acid, cysteine, tyrosine and tryptophan were not significantly changed in any tissue. The results provide evidence supporting the involvement of free radicals in multiple sclerosis.



On the causes of multiple sclerosis

MED. HYPOTHESES (United Kingdom), 1993, 41/2 (93-96)

Evidence on aetiology in multiple sclerosis suggests that the prevalence depends on the interaction of two factors, diet and exposure to visible sunlight. The dietary features which may be beneficial include supplementation with fish oils, avoidance of saturated fats, and the associated intake of antioxidants with unsaturated fatty acids. Inhibition, by antioxidants, of the enzyme lipoxygenase inhibits leukotriene synthesis, and the presence of fish oils leads to the production of leukotrienes with less inflammatory properties. This is of particular importance in the retina where leukotrienes might be the underlying cause of retrobulbar neuritis. The antioxidant properties of vitamin A may also lead to inhibition of leukotriene synthesis. Visible solar radiation could be of benefit therefore by releasing vitamin A from visual pigment rhodopsin. The interaction ot these two factors may explain the epidemiological observations on the prevalence of multiple sclerosis.



Alpha-tocopherol and hydroperoxide content in breast adipose tissue from patients with breast tumors.

Int J Cancer (UNITED STATES) Jul 17 1996, 67 (2) p170-5

The study of the relationship between dietary intake of vitamin E and the risk of breast cancer has not yielded definite conclusions with respect to causality, possibly due to methodological issues inherent to nutritional epidemiology. To avoid the pitfalls of dietary recalls, alpha-tocopherol content of adipose tissue was used as a biochemical indicator of long-term dietary intake of vitamin E. alpha-tocopherol and hydroperoxides were measured in breast adipose tissue obtained at the time of diagnosis from 70 patients with early breast cancer. Thirty women with non-malignant breast tumors served as control. Lipid peroxidation was monitored by quantifying conjugated dienes spectrophotometrically and by assaying hydroperoxides with an iodometric method; alpha-tocopherol was measured by HPLC associated with fluorescence detection. Mean alpha-tocopherol value in breast adipose tissue was significantly lower in breast cancer patients than in control patients, whereas the hydroperoxide content was significantly higher in cancer patients than in controls. The alpha-tocopherol concentration in adipose tissue was not correlated with the clinical status of the patients with respect to age, menopausal status or body mass index. We conclude from this pilot study that breast cancer is associated with a low content of alpha-tocopherol in breast adipose tissue, and with an altered lipid oxidation pattern, which might be related to a low antioxidant status.



Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York, United States)

Cancer Causes and Control (United Kingdom), 1995, 6/5 (407-415)

We sought to determine if specific dietary antioxidants may be particularly effective in reducing breast cancer risk for women reporting family history (FH) of breast cancer in a first-degree relative. Interviews regarding usual diet, health, and family histories were conducted with 262 premenopausal and 371 postmenopausal women with incident, primary breast cancer from western New York (United States). These women were frequency-matched by age and county of residence with community controls. Among premenopausal women, there was a significant interaction between FH and alpha-tocopherol; alpha-tocopherol was associated with significantly decreased risk among FH+ women (adjusted fourth-quartile odds ratio (OR) = 0.01, 95 percent confidence interval (CI) = 0.0-0.3). This association was much weaker for FH- women (OR = 0.7, CI = 0.4-1.2). For FH- women, a significant inverse association was observed between p-carotene and premenopausal breast-cancer risk (OR = 0.4, CI = 0.3-0.5), but not for FH+ women (OR = 0.5, CI = 0.1-4.0). Similar relationships, although not as strong, were noted among postmenopausal women. Although limited by small numbers, these results suggest that biologic mechanisms of tumorigenesis may differ in FH+ and FH- women, and that a-tocopherol may be a potential chemopreventive agent for women with a family history of breast cancer, particularly premenopausal women.



Extraocular, limb and diaphragm muscle group-specific antioxidant enzyme activity patterns in control and mdx mice.

J Neurol Sci (NETHERLANDS) Aug 1996, 139 (2) p180-6

T he mechanisms primarily responsible for the degenerative processes occurring in dystrophic skeletal muscle remain unresolved. The identification of the mechanisms that lead to the complete sparing of extraocular muscle in dystrophinopathies is of particular interest. A number of studies have provided evidence to suggest that the muscle pathology that characterizes muscular dystrophy may be, in part, free radical mediated. In the present study, we examined the antioxidant enzyme status of extraocular, diaphragm and gastrocnemius muscles in control strain and mdx mice. Our results revealed that in the control strain, both extraocular and diaphragm muscles had higher copper/zinc superoxide dismutase, manganese superoxide dismutase and selenium dependent glutathione peroxidase activities as compared to the gastrocnemius. Furthermore, the diaphragm had higher glutathione reductase activity as compared to the gastrocnemius. These findings indicate that the highly aerobic extraocular and diaphragm muscles have higher antioxidant enzyme capacity than the gastrocnemius, a muscle more dependent on anaerobic energy metabolism. Changes in the antioxidant enzyme status of the mdx mouse correlated, in part, with the degree of histopathological involvement of the three muscle groups assessed.



Free radicals, lipid peroxides and antioxidants in blood of patients ith myotonic dystrophy.

J Neurol. 1995 Feb. 242(3). P 119-22

We studied the levels of free radicals, lipid peroxides and antioxidants, as well as superoxide dismutase (SOD) activity in the blood of six patients with myotonic dystrophy (MyD) (mean age 52.8, SD 5.0 years) and seven controls (mean age 48.8, SD 6.3 years). Electron spin resonance was used to assess the free radicals by the spin-trapping method using 5,5-dimethyl-1-pyrroline-1-oxide. The levels of C centre radical (P < 0.05) and H radical (P < 0.05) in blood from the six MyD patients were significantly higher than those in the seven controls. The SOD activities in red blood cells and serum from the six MyD patients showed no significant difference from those in the seven controls. The serum lipid peroxide concentration was increased in five of the MyD patients and tended to increase further as the disease progressed. The serum vitamin E level was low in two patients and in the low normal range in three. Serum coenzyme Q10 was decreased in four patients. The serum selenium level was decreased in two patients and that of serum albumin was decreased in three. Therefore we conclude that increased levels of free radicals and lipid peroxides and decreased antioxidant levels play an important role in the pathogenesis of MyD.



Antioxidants and angiogenetic factor associated with age-related macular degeneration (exudative type)

Journal of Japanese Ophthalmological Society (Japan), 1997, 101/3

To confirm the hypothesis that antioxidants and angiogenetic factors may be associated with the development of age-related macular degeneration (exudative type), we compared serum levels of vitamins A, C, and E and carotinoid, zinc, selenium and b-FGF (basic-fibroblast growth factor) in 35 patients with age-related macular degeneration (exudative type) with the levels in 66 controls. The average serum zinc level was significantly lower in the patient group than in the control group. Serum vitamin E-alpha levels also tended to be lower. Most serum b-FGF levels were below the standard value in each group. Based on the above results, we conclude that subnormal levels of zinc and vitamin E may be associated with the development of age- related macular degeneration.



Studies on the mechanism of early onset macular degeneration in c ynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress

Experimental Eye Research (United Kingdom), 1996, 62/4 (399-408)

Initial investigations done in this laboratory detected increased albumin and decreased glyceraldehyde 3-phosphate dehydrogenase concentrations in the retina of an animal model manifesting early onset macular degeneration. Both glyceraldehyde 3-phosphate dehydrogenase and albumin are markers of oxidative stress in cells. In this study, we used the same animal model to study further biochemical and physiological processes which may be involved in the pathogenesis of early onset macular degeneration in monkeys. We detected 60% lower catalase and glutathione peroxidase activities in the affected retinas suggesting lower antioxidant activities and oxidative stress. One of the consequences of oxidative stress is the production of metallothionein, a low molecular weight protein also induced by high concentrations of heavy metals such as zinc. Metallothionein was detected by RT-PCR in these monkey retinas. However initial quantitative PCR studies on this protein showed that the synthesis of metallothionein in affected retinas appears to be less than in normal controls. The affected retinas also showed a fourfold lower zinc concentration compared with the normal controls. No significant difference, however, could be detected in the zinc concentrations in plasma samples. Since induction of metallothionein synthesis is mediated by transcription factors which require heavy metals such as zinc for binding to specific sites in the DNA, the lowered zinc concentration may, thus, correlate with the lowered metallothionein expression. And since metallothionein is suggested to function as a free radical scavenger, the lowered metallothionein synthesis may consequently contribute to increased peroxidation reactions in the affected retinas. It appears therefore, that oxidative stress and the decreased metallothionein synthesis may be involved in the pathogenesis of early onset macular degeneration in this animal model.



Association of zinc and antioxidant nutrients with age-related maculopathy.

Arch Ophthalmol (UNITED STATES) Aug 1996, 114 (8) p991-7

OBJECTIVE: To quantify relationships between dietary intake of zinc and antioxidant nutrients and early and late age-related maculopathy (ARM). DESIGN: A retrospective longitudinal cohort design using data pertaining to diets in the past (1978-1980), which were assessed retrospectively using a food frequency questionnaire. SETTING: Beaver Dam, Wis. PATIENTS: A 50% random sample of free-living Beaver Dam Eye Study participants, 43 to 86 years of age (N = 1968). MAIN OUTCOME MEASURE: The presence of early and late ARM determined from fundus photography. RESULTS: People in the highest vs lowest quintiles for intake of zinc from foods had lower risk for early ARM (odds ratio = 0.6, 95% confidence interval, 0.4-1.0, P for trend < .05). This relationship appeared to be stronger for some types of early ARM (increased retinal pigment) than for others. Zinc intake was unrelated to late ARM. However, small numbers (n = 30) of people with this condition limit the ability to draw conclusions about this later stage. Levels of carotenoids were unrelated to early or late ARM. Odds for early ARM were lower in people in the highest vs lowest quintiles for the intake of vitamins C or E. However, these associations were not statistically significant. CONCLUSIONS: The data are weakly supportive of a protective effect of zinc on the development of some forms of early ARM. Prospective studies are needed to further evaluate the potential influence of these and other nutritional factors on different types and stages of age-related macular degeneration.



Antioxidant enzymes of the human retina: Effect of age on enzyme activity of macula and periphery

Current Eye Research (United Kingdom), 1996, 15/3 (273-278)

The purpose of this research was to evaluate the effect of age on protective antioxidant enzyme activity of normal fresh cadaver human retina of the macula and periphery. Antioxidant enzymes were assayed in tissue extracts generated from 5 mm trephined punches of retina obtained centered over the macula and the superior midperiphery of normal fresh human cadaver retina. Cadaver tissue was obtained from donors of a wide age range (age 7 to 85 years). The assays were performed within 6 h of enucleation and within 24 h of donor death. Antioxidant enzymes assayed included superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Hexokinase and glucose-6-phosphate dehydrogenase, enzymes not directly involved in protection against oxidative damage, were assayed for comparison. Enzyme specific activities were calculated for the macula and periphery using protein concentration of the extract as the denominator. Using linear regression analysis, over the age range of 25 to 75 years, superoxide dismutase activity of the periphery but not the macula tended to decline with age (p = 0.04, R2 = 0.21). Interindividual variability was high, and variability increased with age. The difference between the macular and peripheral enzyme activities for glutathione peroxidase tended to decline with increasing donor age (p = 0.025, R2 = 0.33). There was no effect of age on the specific activities of catalase, glucose-6-phosphate dehydrogenase, and glutathione reductase. The specific activity of hexokinase from the macula declined with increasing donor age (p = 0.022, R2 = 0.43). Time from death to enucleation or beginning of experiment was not a significant factor. In summary, age does not have an effect on the activity of major antioxidant enzymes of the macula in normal human retina. There is a tendency for an effect of age on peripheral superoxide dismutase activity and the difference between macular and peripheral glutathione peroxidase activity. High interindividual variability of antioxidant enzyme activity exists in humans.



Antioxidant enzymes in RBCs as a biological index of age related macular degeneration

ACTA OPHTHALMOL. (Denmark), 1993, 71/2 (214-218)

The present study was undertaken to assess the levels of antioxidant enzymes in red blood cells of subjects with age-related macular degeneration and age-matched controls. The results obtained show a significant decrease in activities of superoxide dismutase (p < 0.001) and glutathione peroxidase (p < 0.001) as compared to the controls. A good correlation (r =O.99) was also observed between age and decreased activity of antioxidant enzymes in controls, and also correlated well with age related macular degeneration. In conclusion, oxidative stress as assessed by antioxidant enzymes is more pronounced in subjects with age-related macular degeneration as compared to age-matched controls.

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