PubMed Health⌕ Search

Biomedical subjects

A T Diplock

Publications and source records attributed to A T Diplock.

At least 19 recordsLinked to original sources
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↗
PubMed1991

A fibroblast cell culture model to study vitamin K metabolism and the inhibition of vitamin K epoxide reductase by known and suspected antagonists.

The metabolism and antagonism of vitamin K has been studied in cultured fibroblasts. Monolayers of 3T3 mouse fibroblasts (grown in the absence or presence of warfarin or other putative antagonists) were incubated for 24 h with [1',2'-3H2]phylloquinone (K1) or [1',2'-3H2]phylloquinone epoxide (K1O), the cells harvested and lipid extracts fractionated by high performance liquid chromatography. [3H]K1 was converted to [3H]K1O (about 20% of [3H] lipids) and to unidentified polar metabolites (30%). [3H]K1O was converted to [3H]K1 (3%) and to polar metabolites (50%). Cells grown with warfarin showed a marked increase in the [3H]K1O:K1 ratio and in the proportion of polar metabolites. The metabolic interconversion of K1 and K1O and inhibitory response to warfarin provide evidence for a fibroblast pathway analogous to the vitamin K-epoxide cycle in the liver. From the K1O:K1 ratios it was possible to grade the antagonism of vitamin K epoxide reductase activity by known and suspected inhibitors. Inhibitory ratios were seen for racemic warfarin down to 10(-8) M. S-warfarin was a more potent antagonist than the R-enantiomer. Consistently low K1O:K1 ratios were observed for N-methyl-thiotetrazole and antibiotics with (moxalactam) or without (cefotaxime) this side chain suggesting that none of these compounds are direct inhibitors of vitamin K epoxide reductase. Fibroblasts grown in cell culture provide a useful model to study the extrahepatic role of vitamin K and the mode of action of vitamin K antagonists.

Animals↗
PubMed1991

Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium.

Selenium and seleno dependent glutathione peroxidase (GPX) deficiency has been described in endemias of myxedematous cretinism. In northern Zaire, a selenium supplementation trial has been conducted. Beside correcting the GPX activity, two months of selenium supplementation was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects. These results further support a role of selenium in thyroid hormone metabolism. In an iodine deficient area, this selenium deficiency could lead to opposite clinical consequences: protect the general population and the fetus against iodine deficiency and brain damage; and in turn, favour the degenerative process of the thyroid gland leading to myxoedematous cretinism.

Child↗
PubMed1990

Mineral insufficiency and cancer.

There are excellent theoretical reasons why the mineral nutrients selenium, manganese, copper and zinc, known as the antioxidant minerals, may be involved in the prevention of cancer aetiogenesis. The biochemistry is discussed of the part played by the antioxidant minerals, in the wider context of the other dietary antioxidants vitamins A, E and C, and beta carotene, in preventing tissue damage caused by activated metabolites of oxygen. The likely part played by these oxygen metabolites is described and a detailed review given of the evidence that suggests a role for antioxidant minerals, notably selenium, in preventing carcinogenesis in a range of animal models. There follows a summary of the emerging epidemiological evidence that suggests clearly that low selenium intake is a risk factor in the aetiology of human cancer.

Animals↗
PubMed1990

Iodine and selenium deficiency associated with cretinism in northern Zaire.

Selenium status was determined in an endemic-goiter area and in a control area of Zaire. Compared with the reference values of a noniodine-deficient area, serum selenium in subjects living in the core of the northern Zaire endemic-goiter belt (Karawa villages) was seven times lower in 52 school-children and similarly low in 23 cretins; erythrocyte glutathione peroxidase (RBC-GPX) was five times lower in schoolchildren and still two times lower in cretins (P = 0.004). In a less severely iodine-deficient city of the same endemia (Businga), selenium status was moderately altered. RBC-GPX activity was linearly associated with serum selenium concentration up to a value of 1140 nmol/L and leveled off at approximately 15 U/g Hb at greater selenium concentration. At Karawa villages, selenium supplementation normalized both the serum selenium and the RBC-GPX. This combined iodine and selenium deficiency could be associated with the elevated frequency of endemic myxedematous cretinism in Central Africa.

Adolescent↗
PubMed1989

Iron overload and the predisposition of cells to antioxidant consumption and peroxidative damage.

We have investigated the effects of iron overload in vivo on the tocopherol levels and the extent of lipid peroxidation in rat liver microsomes and their response to subsequent oxidative stress in vitro. The results demonstrate a direct correlation between consumption of antioxidant defences and the induction and extent of malondialdehyde production in microsomes prepared from iron-loaded rats. The data are consistent with the requirement for iron (II)/iron (III) ratios in lipid peroxidation in control microsomes.

Animals↗
PubMed1977

Interactions of tocopherols and ubiquinones with monolayers of phospholipids.

1. The penetration of alpha-tocopherol and seven of its derivatives, and five compounds in the ubiquinone series, having differing chain lengths, into monolayers at the air/water interface of 11 different synthetic phospholipids and cholesterol was investigated; the properties of mixed monolayers of the tocopherols and of ubiquinones with phospholipids were also studied. 2. Penetration of alpha-tocopherol into diarachidonylglycerylphosphorycholine was approximately constant for molar ratios of tocopherol/phospholipid ranging from 0.4:1.0 to 2.0:1.0. 3. Tocopherols with shorter or longer side chains than alpha-tocopherol had a lesser ability to penetrate monolayers of phospholipid molecules with 16 or more carbon atoms in their acyl chains. 4. All the tocopherols penetrated more readily as unsaturation in the phospholipids was increased, and their penetration into mixed monolayers of phospholipids was greatly facilitated by the presence of relatively small quantities of unsaturated phospholipid molecules. 5. There was relatively little interaction between the tocopherols and cholesterol, or between the ubiquinones and phospholipids. 6. The possible significance of the observed interactions between alpha-tocopherol and polyunsaturated phospholipids is discussed in relation to the biochemical actions of alpha-tocopherol in vivo. 7. It is suggested that fluidity of the lipid bilayer in membranes containing polyunsaturated phospholipids may allow alpha-tocopherol to interact in a dynamic manner with a number of phospholipid molecules.

Membranes↗