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Biomedical subjects

A T Diplock

Publications and source records attributed to A T Diplock.

At least 37 records · Page 2Linked to original sources
PubMed1995

Levels of antioxidant nutrients in plasma and low density lipoproteins: a human volunteer supplementation study.

A human supplementation study was undertaken in order to investigate the correlation between the intake of individual daily dosages of vitamin E (300 mg), vitamin C (250 mg), or beta-carotene (15 mg) of eight week duration and their uptake in vivo in plasma and LDL. The effects of a combined supplement of vitamin E, vitamin C and beta-carotene (Redoxon protector-75 mg, 150 mg, 15 mg respectively) were also investigated. The results show that on supplementation with the individual antioxidants the increases in plasma alpha-tocopherol:cholesterol levels lie in the 1.5-2 fold range and the beta-carotene:cholesterol ratios give a mean 3.5 fold enhancement. The combined supplement containing the same level of beta-carotene as the single dosage achieved comparative levels of uptake in plasma. The level of plasma vitamin C appears to be maximal at about 100 microM regardless of the pre-supplementation level.

Adult↗
PubMed1994

Is there a significant role for lipid peroxidation in the causation of malignancy and for antioxidants in cancer prevention?

alpha-Tocopherol (alpha-T) uptake and its relationship to cell proliferation and lipid peroxidation was studied in a baby hamster kidney cell line (BHK-21/C13) and its polyoma virus-transformed malignant counterpart (BHK-21/PyY cells). The principal findings were as follows. (a) The level of lipid peroxidation judged by malondialdehyde (MDA) measurement by HPLC, was higher in the transformed cells than in the nontransformed cells. Oxidative stress by 374 mM Fe3+/10 mM ADP caused a significant increase in the level of MDA of a similar magnitude in both cell types. Addition of 7, 14, and 21 mM alpha-T caused no diminution of the MDA level in the unstressed cells and abolished the increase in MDA seen in the stressed cells. (b) The endogenous level of alpha-T in the transformed cells was lower than in the nontransformed cells and all of the measurable alpha-T in these cells was destroyed by the oxidative stress. Supplementation of the cells with alpha-T caused an increase in the level of alpha-T that was proportional to the level of inclusion of alpha-T in the medium. (c) Growth was stimulated by 7 and 14 mM alpha-T but not by the higher levels of inclusion in the medium. The growth stimulation was much larger in the transformed cells (163% of growth in the unsupplemented medium) than in the nontransformed cells (120%). (d) These results demonstrate that, in this cell system, the growth-stimulating ability of alpha-T is unrelated to the ability of alpha-T to control lipid peroxidation and that the level of peroxidation is increased in the malignant state. The difference between the findings reported here and earlier work showing increased levels of alpha-T and decreased levels of peroxidation in transformed malignant cells is discussed and possible explanations for it are advanced.

Animals↗
PubMed1994

Summary of the round table discussion on strategies for cancer prevention: diet, food, additives, supplements, and drugs.

A Round Table Discussion was held at the Fourth International Conference on Anticarcinogenesis and Radiation Protection. Scientists from government and academia were brought together to discuss the evidence for the preventive effect of foods, specific nutrients and drugs against cancer, and the most appropriate methods of initiating nutritional cancer prevention activities to improve the health of the public. The panel reviewed the epidemiological evidence of the role of diet and specific micronutrients for the prevention of cancer, the doses of specific micronutrients required for preventive effects and their safety, the evidence for aspirin as a chemopreventive agent, the issue of foods versus specific micronutrients in the prevention of cancer, food safety, and approaches to prevention such as food fortification or dietary supplements. The remarks of the panel members are summarized.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Malondialdehyde formation in liver mitochondrial and microsomal fractions of vitamin E- and selenium-deficient rats as a function of alpha-tocopherol level: the effect of treatment in vitro with iron.

Weanling rats were given diets with adequate vitamin E and selenium or deprived of one or the other or both, nutrients. After 28 days, liver mitochondrial and microsomal fractions were prepared and alpha-tocopherol (alpha-T) and selenium measured. alpha-Tocopherol fell by eight-fold in the doubly deficient rats and selenium fell three-fold. Malondialdehyde (MDA) was found to be undetectable by a sensitive HPLC method. The fractions were subjected to peroxidative stress in in vitro using 0.5 mM Fe2+/10 mM ADP, and MDA and alpha-T were measured at intervals during 30 min. The results showed that in the mitochondrial fractions there was a lag time of at least 2 min before peroxidation became significant, during which time most of the alpha-T was consumed. In the microsomal fraction the lag phase was very short prior to the establishment of a linear rate of peroxidation, although little alpha-T was used up. It was concluded that the mitochondrial fraction withstood the peroxidative challenge better than the microsomal fraction even though the initial level of alpha-T in the microsomal fraction was about double that in the mitochondrial fraction. Selenium deficiency had no effect on the length of the lag phase of the fractions which therefore appears to be a characteristic of mitochondrial or microsomal fractions.

Adenosine Diphosphate↗
PubMed1993

alpha-Tocopherol uptake and its influence on cell proliferation and lipid peroxidation in transformed and nontransformed baby hamster kidney cells.

alpha-Tocopherol (alpha-T) uptake and its relationship to cell proliferation and lipid peroxidation was studied in a baby hamster kidney cell line (BHK-21/C13) and its polyoma virus-transformed malignant counterpart (BHK-21/PyY cells). The principal findings were as follows. (i) The level of lipid peroxidation, judged by malondialdehyde (MDA) measurement by HPLC, was higher in the transformed cells than in the nontransformed cells. Oxidative stress by 374 microM Fe3+/10 mM ADP caused a significant increase in the level of MDA of a similar magnitude in both cell types. Addition of 7, 14, and 21 microM alpha-T caused no diminution of the MDA level in the unstressed cells and abolished the rise in MDA seen in the stressed cells. (ii) The endogenous level of alpha-T in the transformed cells was lower than in the nontransformed cells and all the measurable alpha-T in these cells was destroyed by the oxidative stress. Supplementation of the cells with alpha-T caused a rise in the level of alpha-T proportional to the level of inclusion of alpha-T in the medium. (iii) alpha-Tocopheryl quinone in the transformed cells was unaffected by oxidative stress and in the nontransformed cells stress caused a large increase in this metabolite when alpha-T was included at the 21 microM level. (iv) Growth was stimulated by 7 and 14 microM alpha-T but not by the higher level of inclusion in the medium. The growth stimulation was much larger in the transformed cells (163% of growth in the unsupplemented medium) than in the nontransformed cells (120%). (v) These results demonstrate that, in this cell system, the growth-stimulating ability of alpha-T is unrelated to the ability of alpha-T to control lipid peroxidation and that the level of peroxidation is increased in the malignant state.

Adenosine Diphosphate↗
PubMed1993

Current status of antioxidant therapy.

There is evidence that free radical damage contributes to the aetiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. In this review we are not concerned with tissue damage in vivo induced directly by radicals from exogenous sources, such as air pollutants and tobacco smoke, high-pressure oxygen, irradiation, or through the metabolism of certain solvents, drugs, and pesticides. Rather, we address some of the disease states associated with increased oxidative stress from endogenous sources and the possible therapeutic advantage of the antioxidant treatment. This raises the question of the antioxidant status of individuals and its role in protection against amplification of certain disease processes. We have chosen to concentrate mainly on coronary heart disease, reperfusion injury, and organ storage for transplantation.

Animals↗
PubMed1993

Indexes of selenium status in human populations.

This paper considers the factors that affect the bioavailability of selenium to human populations and describes briefly the consequences of an inadequate dietary intake of selenium in the Peoples' Republic of China and in Zaire. A review of human blood selenium concentrations worldwide reveals very large differences in the apparent dietary status of individuals in different areas. The question is raised as to whether blood selenium measurement is a reliable index of actual selenium status in terms of bioavailability and function of the element. It is concluded that the preferred indexes of human selenium status are blood, or plasma and/or serum, concentrations of the element and the level of activity of the selenium-dependent enzyme glutathione peroxidase in erythrocytes or in plasma. Several important caveats to this conclusion are mentioned and other means of assessing selenium status are also considered.

Biological Availability↗
PubMed1993

Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects.

Studies were performed to assess the role of combined selenium and iodine deficiency in the etiology of endemic myxedematous cretinism in a population in Zaire. One effect of selenium deficiency may be to lower glutathione peroxidase activity in the thyroid gland, thus allowing hydrogen peroxide produced during thyroid hormone synthesis to be cytotoxic. In selenium-and-iodine-deficient humans, selenium supplementation may aggravate hypothyroidism by stimulating thyroxin metabolism by the selenoenzyme type I iodothyronine 5'-deiodinase. Selenium supplementation is thus not indicated without iodine or thyroid hormone supplementation in cases of combined selenium and iodine deficiencies.

Adolescent↗
PubMed1992

Variable alpha-tocopherol stimulation and protection of glutathione peroxidase activity in non-transformed and transformed fibroblasts.

Studies on glutathione metabolism in an established baby hamster kidney cell line (BHK-21/C13) and in its polyoma virus-transformed counterpart (BHK-21/PyY), have revealed a significant stimulation of intracellular glutathione peroxidase activity (Se-independent plus Se-dependent) by alpha-tocopherol supplementation (14 microM). This stimulation was found to be much greater in the transformed cells. Other GSH-requiring enzyme activities (namely glutathione reductase and glutathione transferase) were unaltered by alpha-tocopherol treatment, suggesting a degree of specificity in its action on GSHpx. In unsupplemented growth media, the GSHpx activity in both cell lines was significantly decreased by an oxidative stress. However, the same stress applied to the alpha-tocopherol-supplemented cells had no effect on the stimulated GSHpx activity, suggesting a protection afforded by the alpha-tocopherol.

Animals↗
PubMed1992

Tolerance and safety of vitamin E: a toxicological position report.

From numerous publications on the "prophylactic" and "therapeutic" use of vitamin E, it may be concluded that the toxicity of vitamin E is very low. It has been demonstrated in animal experiments that vitamin E has neither mutagenic, teratogenic nor carcinogenic properties. Based on studies in humans, a daily dosage of 100-300 mg vitamin E can be considered harmless from a toxicological point of view. Using double-blind studies involving a large number of subjects, it has been demonstrated that large oral doses of up to 3,200 USP-Units/day led to no consistent adverse effects. From a large body of published data, dosage ranges have been deduced which can be characterized as safe for human subjects even where their use extends over a long period of time. It should, however, be noted that oral intake of high levels of vitamin E can exacerbate the blood coagulation defect of vitamin K deficiency caused by malabsorption or anticoagulant therapy. High levels of vitamin E intake are, therefore, contraindicated in these subjects.

Animals↗
PubMed1992

Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population.

OBJECTIVE: Severe selenium deficiency has been documented in northern Zaïre, already known as one of the most iodine deficient regions in the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted in this area to evaluate the effects of a selenium supplementation on thyroid diseases. DESIGN: Placebo or selenium 50 micrograms as selenomethionine was administered once daily for 2 months. Blood and urine samples were collected before and after supplementation. PATIENTS: Fifty-two healthy schoolchildren from northern Zaire. MEASUREMENT: Selenium status, thyroid function and urinary iodide were determined. RESULTS: After 2 months of selenium supplementation, mean +/- SD serum T4 decreased from 73.1 +/- 45.4 to 48.3 +/- 23.7 nmol/l (P less than 0.001), serum FT4 from 11.8 +/- 6.7 to 8.4 +/- 4.1 pmol/l (P less than 0.01), and serum rT3 from 124 +/- 115 to 90 +/- 72 pmol/l (P less than 0.05), without significant change in serum T3 and serum TSH. CONCLUSION: Deiodinase type I which has been shown to be a seleno-enzyme could account for the changes in thyroid hormones in our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism in humans. Selenium could be an important cofactor in the clinical picture of iodine deficiency in Central Africa and could be involved in the aetiology of both forms of cretinism.

Administration, Oral↗
PubMed1992

Variable alpha-tocopherol stimulation and protection of glutathione peroxidase activity in established and malignant fibroblasts.

Studies on glutathione (GSH) metabolism in an established baby hamster kidney fibroblast cell line (BHK-21/C13) and in its polyoma virus-transformed counterpart (BHK-21/PyY) have revealed a significant stimulation of intracellular GSH peroxidase (GSHpx) activity (selenium-independent plus selenium-dependent) by alpha-tocopherol supplementation (14 microM). This stimulation was found to be much greater in the transformed cells. Other GSH-requiring enzyme activities (i.e. GSH reductase and GSH S-transferase) were unaltered by alpha-tocopherol treatment, suggesting a degree of specificity in its action on GSHpx. In unsupplemented growth media, the GSHpx activity in both cell lines was significantly decreased by oxidative stress. However, the same stress applied to the alpha-tocopherol-supplemented cells had no effect on the stimulated GSHpx activity, suggesting that some protection was afforded by the alpha-tocopherol.

Animals↗
PubMed1991

Antioxidant nutrients and disease prevention: an overview.

Interest in free radical events has stimulated speculation that their disorder may be involved in a number of diseases. The reduction of dioxygen to water involves several active intermediates. The control of this depends on the integrity of an enzymatic system that requires adequate intake of selenium, copper, zinc, and manganese; if their level of intake is low, proliferation of active oxygen metabolites may occur. Targets for attack are DNA, proteins, and polyunsaturated phospholipids. Peroxidation of polyunsaturated phospholipids will result in disruption of membrane architecture. Vitamin E, perhaps with ascorbic acid, can prevent this, and vitamin A and beta-carotene also intervene. The implication of this in the etiology of a number of diseases depends on theory and on evidence linking low intake of the antioxidant nutrients with a high disease incidence. Improvements in epidemiology have resulted in glimpses into what may prove to be links between diet and disease.

Antioxidants↗