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Biomedical subjects

J Neve

Publications and source records attributed to J Neve.

36 records · Page 2Linked to original sources

Comparison of effects of chronic inflammation and long-term prednisolone administration on zinc metabolism in rats.

It is well known that plasma zinc is depressed in animals following administration of endotoxin, endogenous pyrogen, interleukin-1, and glucocorticoids. The modification is related to an induction of liver metallothionein causing an accumulation of the element in this organ. The changes in zinc metabolism induced by adjuvant arthritis in rats evidenced a redistribution of body zinc with a rapid and sustained decrease in plasma zinc that occurred simultaneously with an increase in liver zinc levels, and slower modification in erythrocyte and femur zinc concentrations. These effects were compared to those induced by a long-term corticosteroid administration in healthy rats. Male Wistar rats received either a commercially available complete maintenance diet or the same diet enriched with prednisolone at a level providing 1 mg prednisolone/kg body weight. Groups of animals were sacrificed after 3 or 5 weeks' treatment. Ingested food quantity, total body weight, total serum proteins and serum albumin were similar in treated and control rats. No significant modifications in parameters of zinc status could be observed after 3 weeks of treatment. However after 5 weeks, plasma zinc was significantly lower in treated rats as compared to controls, but modifications in liver, erythrocyte and femur zinc did not reach statistical significance. Changes induced by long-term corticosteroid administration are therefore less intense than those due to the inflammatory process of adjuvant arthritis.

Adrenal Cortex Hormones↗

[Selenium and cardiovascular pathology].

Selenium deficiency has established implications in cardiovascular diseases, particularly on cardiac muscle integrity. The essential trace element takes part not only in the direct protection of endothelial cells against the accumulation of aggressive oxygen species, but also in the biosynthesis of arachidonic acid derivatives involved in platelet and leucocyte functions, or in the regulation of cholesterol. Moreover, it prevents toxic effects of cadmium and mercury, and modulates the active transport of calcium. Some clinical investigations have underlined its importance in the cardiac function and the prevention of coronary atherosclerosis, and several recent prospective epidemiological studies have attributed to selenium deficiency a greater incidence of cardiovascular diseases. Further studies should be devoted to the influence of marginal deficiency in this trace element whose optimal requirement does not seem to be met by the usual dietary intake.

Cardiovascular Diseases↗

[Usual values of selenium and glutathione peroxidase in a Belgian population].

Several biological parameters for assessing selenium status have been determined in years 1985-1986 in a large Belgian population group, males and females 0 to 92 years old, representative from Brussels and surroundings. In 145 people, 20 to 79 years old, mean concentrations were: 1.06 +/- 0.15 mumol Se/l plasma, 5.0 +/- 1.1 nmol Se/g Hb in erythrocytes and 7.4 +/- 2.0 mu/g Hb for the selenodependent glutathione peroxidase activity measured in erythrocytes (mean +/- standard deviation). Values for urine selenium have a disymmetric distribution and range from 0.05 to 0.65 mumol Se/g creatinine. No difference was evidenced in this group according to sex and age. Children below 20 years and elderly above 80 years have decreased plasma and erythrocyte selenium concentrations but glutathione peroxidase is not modified. These blood selenium concentrations are lower than those determined in a similar population group in years 1980-1981, suggesting a progressive decrease in selenium intake. The concentrations of the biological parameters are not correlated together except in selenium deficient patients having plasma selenium less than 0.75 mumol/l: a significant correlation is observed between plasma selenium and erythrocyte glutathione peroxidase activity, that becomes more intense with decreasing plasma selenium. Finally, two recent investigations are described where a significant response in platelet glutathione peroxidase was obtained during a 60 days selenium supplementation with 100 to 200 micrograms selenium per day, suggesting that usual selenium intake in Belgium (50 micrograms per day) is marginally deficient.

Adolescent↗

Circadian variations in plasma zinc and cortisol in man.

Circadian variations of zinc and cortisol concentrations in plasma were studied in six healthy adult men. Three of them were tested over two different 24-h periods. Results were analyzed by computerizing a best-fit curve for each 24-h profile. Plasma zinc displayed a morning peak between 8.00 and 9.00 a.m. followed by an almost linear decline throughout the day with lowest values observed shortly before 6.00 p.m. A transitory increase occurred between 6.00 p.m. and 8.00 p.m. followed by a slow decrease reaching its nadir around midnight. Thereafter zinc increased steadily until 8.00 a.m. A similar profile was observed in a seventh subject who was undergoing therapeutic starvation for obesity (fifth day of the starvation period). In all subjects the time course of plasma cortisol fluctuations paralleled that of zinc. Our results confirm the existence of a circadian rhythm in plasma zinc independent of zinc intake and temporally related to the circadian rhythm of cortisol.

Adult↗

Selenium status in relation to clinical variables and corticosteroid treatment in rheumatoid arthritis.

Plasma selenium levels, erythrocyte selenium levels and activity of the selenoenzyme glutathione peroxidase in erythrocytes were determined in patients with rheumatoid arthritis (RA) and acute inflammatory arthritis. Results were compared with those from age and sex matched controls. These variables were not statistically different from controls in patients with inflammatory arthritis and in patients with RA not treated with corticosteroids. No correlation was found in RA between plasma selenium biological variables of inflammation and most clinical indices of disease severity. Therefore, acute or chronic inflammation was not the main factor that accounted for low plasma selenium levels in RA. Corticosteroid treatment, particularly at high doses (20-60 mg prednisolone/day), was significantly related to the depressed plasma selenium levels of some patients with RA. The mechanisms underlying this modification remain poorly understood.

Acute Disease↗

Plasma and erythrocyte zinc, copper and selenium in cystic fibrosis.

Plasma and erythrocyte zinc, copper and selenium were measured in 20 cystic fibrosis children, aged 7 to 19 years. Mean plasma zinc and copper levels were not different from those in age-matched controls but very low zinc levels occurred sporadically. Plasma zinc concentrations were significantly lower in patients with moderate-to-severe growth retardation and with severe pulmonary disease as compared to patients without growth failure and with moderate pulmonary disease. Mean erythrocyte zinc (40.8 micrograms/g Hb +/- 9.2) and copper levels (3.56 micrograms/g Hb +/- 0.50) were very significantly increased (30.4 micrograms/g Hb +/- 5.2 and 2.73 micrograms/g Hb +/- 0.30 respectively, for age-matched controls). Mean plasma and erythrocyte selenium levels (63 ng/ml +/- 15 and 329 ng/g Hb +/- 86) were significantly lower than those in age-matched controls (82 ng/ml +/- 13 and 404 ng/g Hb +/- 116). The trace element concentrations in erythrocytes are discussed in relation to the activities of the copper- and zinc-containing enzyme superoxide dismutase and the seleno-enzyme glutathione peroxidase. We consider that more data on trace element metabolism in CF should be collected before specific supplementation is considered.

Adolescent↗

Protein-energy malnutrition and anemia in Kivu.

Protein-energy malnutrition in Kivu is associated with a discrete normocytic, normochromic anemia. An attempt to define the physiopathology of this anemia disclosed the following results. As compared with local controls, both iron and total iron binding capacity were low, but with siderophilin saturation and sideroblast counts either normal or elevated; serum and erythrocyte folate was normal, plasma vitamin B12 was normal or elevated, and serum ascorbic acid was normal or elevated. The riboflavin nutritional status was normal. During refeeding, iron and riboflavin deficiencies became apparent. Characteristic findings on admission were the presence of giant erythroblasts and a diminished erythrocyte survival time implicated to an intracorpuscular hemolysis. Two results from the present study could contribute to explanation for the aforementioned abnormalities: low plasma vitamin E levels and, perhaps more importantly, low plasma selenium levels. In conclusion, the anemia of protein-energy malnutrition, as observed in Kivu, is a classifiable nonadaptive anemia that cannot be explained by isolated iron or vitamin deficiencies and whose physiopathology is distinct from that of the anemia of chronic disorders. It is suggested that a selenium deficiency may play an important role in the pathogenesis of this anemia.

Anemia↗

Clinical implications of trace elements in endocrinology.

The implications of essential trace elements in endocrinological processes, mainly thyroid function, growth, gonadal function, adrenal hormones, prolactin, glucose homeostasis, calcium-phosphorus metabolism, and thymulin activity, are reviewed. Most concerned elements in this field include iodine, zinc, selenium, copper, chromium, manganese and vanadium. The minerals are powerful modulators of several physiological functions that can be considerably perturbed in deficiency states. The resulting biochemical and clinical modifications can be prevented and/or corrected by adequate supplementation. Sometimes, however, they act like pharmacological agents when their beneficial effects are not the result of a correction of a nutritional deficiency state. Their potentialities as therapeutic agents are perfectly described in many cases, but some indications deserve further investigations.

Adult↗

Effects of acute prednisolone administration on plasma and liver copper in rats with adjuvant arthritis.

Several studies in animals and humans have shown that copper metabolism could be affected by inflammation or by corticosteroids. The relative importance of these two factors, often imbedded in clinical practice, was assessed by investigating the effects of acute prednisolone administration (30 mg/kg, ip) on healthy and adjuvant arthritis rats. Plasma copper levels were significantly higher in arthritic rats compared to healthy animals, whereas there was a slight, but nonsignificant increase in liver copper. Acute prednisolone administration in healthy rats resulted in a significant increase in plasma copper (10-15%) as early as 4 h after corticosteroid administration, which was maintained for 12 h. In arthritic rats, the response was much higher (25-40%), but somewhat delayed and shorter. Liver copper was not clearly modified by prednisolone treatment in both groups. This time-controlled study showed that acute prednisolone administration increased plasma copper in both healthy and arthritic rats, but in different ways, indicating that inflammation and corticosteroids may act synergistically.

Animals↗

[The nutritional importance and physiopathology of molybdenum in man].

Molybdenum is an essential trace element taking part in the active site of three human enzymes: xanthine oxidase, aldehyde oxidase and sulfite oxidase, playing a role in the detoxification of the organism and/or the production of important intermediary products. The perturbation of the first two enzymes has no established clinical consequence, but a decrease in activity of the third one is harmful for the organism, particularly the nervous system during pre- or post-natal development. The anomalies in the function of these enzymes are generally inherited and linked to the impaired production of the molybdenum cofactor, an organic molecule complexed to the element in the active site. However, several pathological cases in animals and one case in man have been clearly attributed to molybdenum deficiency. It is the reason why molybdenum supplementation has been recommended in long term total parenteral nutrition in infants and adults.

Humans↗

[The nutritional importance and pharmacologic effects of cobalt and vitamin B 12 in man].

Cobalt is an unique trace element for man as it can only reveal its essential properties if provided directly as its biological active form, cobalamin or vitamin B12, the daily requirement of which is 1 to 2 micrograms in adults. This vitamin takes part in the activity of the enzyme methylmalonyl coenzyme A mutase, involved in the conversion of propionyl CoA to succinyl CoA, an intermediary product of the citrate cycle, and of the 5-methyltetrahydrofolate: homocystein methyltransferase, working in the metabolism of methionin and in DNA synthesis. Vitamin B12 deficiency is responsible for a megaloblastic anemia called pernicious anemia and for specific neurological disorders that can be corrected by adequate supplementation. Inorganic cobalt salts can therefore not be considered as essential micronutrients for man, but being able to induce polycythemia, they have a pharmacological property that was recommended in the treatment of various anemias, and they are also used in the management of cyanide poisoning.

Cobalt↗

[Metabolic disorders of essential trace elements related to rheumatic disorders].

Trace elements are usually considered as "alternative" therapy. The present work is devoted to the analysis of the modifications in zinc, copper and selenium status in rheumatic diseases. The effect of the usual drug treatment is further studied as well as the therapeutic opportunities in "classic" medicine.

Copper↗

[Some factors influencing the bioavailability of zinc in oral pharmaceutical dosage forms].

Absorption and distribution of zinc in 6 dosage forms were determined in 10 subjects by performing a pharmacokinetic study of the serum zinc profile after oral administration of a dose corresponding to 45 mg elemental zinc. The aim of this study was to document the influence on zinc bioavailability of factors such as the chemical form of zinc, the pharmaceutical form, and the division of the administered dose. The pharmacokinetic parameters indicate for gelatin capsules without excipients taken in a non divided dose better performances for zinc gluconate in comparison to zinc sulfate. Concerning the pharmaceutical form, little difference is observed between an aqueous solution and a gelatin capsule for zinc sulfate and a non divided dose; on the contrary, a commercial gelatin capsule containing zinc gluconate with various excipients show better performances than gastro-resistant tablets when zinc intake is 3 times 15 mg. Finally, the division in 3 parts of the dose of zinc sulfate given in gelatin capsules very significantly improves zinc absorption. These results demonstrate the interest of the developed pharmacokinetic method in the assessment of zinc bioavailability in different pharmaceutical dosage forms.

Administration, Oral↗