[The plasma antioxidant status and trace elements in patients with familial hypercholesterolemia treated with LDL-apheresis]. / Statut plasmatique en antioxydants et en oligoéléments de patients atteints d'hypercholestérolémie familiale traités par LDL-aphérèse.

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamin A and E and beta-carotene. Trace elements such as selenium, zinc and copper are involved in the activity of antioxidant enzymes: glutathione peroxidase and superoxide dismutase. The aim of this work was to determine the antioxidant and trace elements status of patients with very severe hypercholesterolemia and who were treated by dextran sulphate low density lipoprotein apheresis, in comparison with two control populations: one constituted by normocholesterolemic subjects and the other by hypercholesterolemic patients before treatment. Our results showed that, as compared with normocholesterolemic subjects, patients treated by LDL-apheresis were not deficient in vitamin E, beta-carotene and copper but had low plasma levels of selenium, zinc and vitamin A. The low selenium and vitamin A levels were due to the treatment by LDL-apheresis by itself, while the hypercholesterolemia of these patients might have provoked the low plasma levels of zinc. This study pointed out the interest of a supplement of selenium, zinc and vitamin A in patients treated by LDL-apheresis.

Antioxidant status of hypercholesterolemic patients treated with LDL apheresis.

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamins A and E and beta-carotene. Trace elements, such as selenium, zinc, and copper, are involved in the activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. The aim of this study was to determine the antioxidant and trace element status of patients with severe hypercholesterolemia who had been treated with dextran-sulphate low-density lipoprotein apheresis in comparison with two control populations, normocholesterolemic subjects and untreated hypercholesterolemic patients. Our results showed that, patients treated with LDL apheresis, compared with normocholesteromic subjects, were not deficient in vitamin E, beta-carotene, and copper, but had lower plasma levels of selenium, zinc, and vitamin A. The low selenium and vitamin A levels were due to the LDL-apheresis treatment, and the hypercholesterolemia might have provoked the low plasma levels of zinc. The study pointed out the potential benefits of supplemental selenium, zinc, and vitamin A in patients being treated with LDL apheresis.

Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure.

A profound imbalance between oxidants and antioxidants has been suggested in uremic patients on maintenance hemodialysis. However, the respective influence of uremia and dialysis procedure has not been evaluated. Circulating levels of copper-zinc superoxide dismutase (CuZn SOD), glutathione peroxidase (GSH-Px), and reductase (GSSG-Rd), total GSH and GSSG were determined in a large cohort of 233 uremic patients including 185 undialyzed patients with mild to severe chronic renal failure, and 48 patients treated by peritoneal dialysis or hemodialysis. Compared to controls, erythrocyte GSH-Px and GSSG-Rd activities were significantly increased at the mild stage of chronic uremia (p < .001), whereas erythrocyte CuZn SOD activity was unchanged, total level of GSH and plasma GSH-Px activity were significantly decreased, and GSSG level and GSSG-Rd activity were unchanged. Positive Spearman rank correlations were observed between creatinine clearance and plasma levels of GSH-Px (r = .65, p < .001), selenium (r = .47, p < .001), and GSH (r = .41, p < .001). Alterations in antioxidant systems gradually increased with the degree of renal failure, further rose in patients on peritoneal dialysis and culminated in hemodialysis patients in whom an almost complete abolishment of GSH-Px activity was observed. In conclusion, such disturbances in antioxidant systems that occur from the early stage of chronic uremia and are exacerbated by dialysis provide additional evidence for a resulting oxidative stress that could contribute to the development of accelerated atherosclerosis and other long-term complications in uremic patients.

[Nutritional biological markers of deficiencies of zinc, copper and selenium]. / Marqueurs biologiques nutritionnels des carences en zinc, cuivre et sélénium.

Direct and indirect indices used for the assessment of copper, zinc or selenium status in humans are reviewed. Variations, advantages and disadvantages are discussed. Despite the numerous indices, none of them provide a satisfactory assessment of the nutritional status for these trace elements. The best indices are probably serum zinc and alkaline phosphatase for the assessment of zinc status, serum selenium for the assessment of selenium status and possibly erythrocyte Cu-Zn superoxide dismutase for the assessment of copper status.

[Oxidative stress in 29 HIV seropositive patients. Two-year results of a double-blind trial of diethyldithiocarbamate versus placebo]. / Stress oxydatif chez 29 sujets séropositifs. Résultats à 2 ans d'une étude en double insu diéthyldithiocarbamate versus placebo.

Among 29 seropositive subjects who had participated in the HIV 87 therapeutic trial (Mérieux laboratories), the oxidative stress was evaluated at 24 months in 16 treated with diethyldithiocarbamate (dithiocarb) and in 13 who had received the placebo. No significant difference was found between these two groups, whereas the existence of an oxidative stress has been confirmed in seropositive subjects compared with controls.

[Concentration of zinc, copper, selenium and aluminium in nutritive solutions for parenteral administration]. / Concentration de Zn, Cu, Se et Al dans des solutés nutritifs utilisés par voie parentérale.

Total parenteral nutrition (TNP) therapy is widely used. However the quantitative requirements or the toxicity of trace elements in parenteral solutions are difficult to assess. This paper deals with a study performed by the Trace Element Commission of the Société Française de Biologie Clinique. Trace metals (zinc, copper, selenium and aluminium) which are mainly involved in TPN solutions are analyzed in 12 different parenteral nutrition solutions commercially available. This multicentric assay (5 different sites of analysis) shows that a slight pollution can be noted for nearly all the solutions examined. But at this level (10 mumol/l for the most concentrated solution), the zinc intake cannot induce any toxicity. For copper and selenium the results indicated a negligible pollution. Small-volume solutions added with zinc, copper and selenium are correctly supplemented. As regard aluminium pollution, 4 solutions among 12 contain non negligible amounts of aluminium. The consequences of this TPN overload especially for young infants, indicate that the struggle against this pollution has to be strengthened.

Correction of selenium deficiency in hemodialyzed patients.

Selenium is an essential trace element important for glutathione peroxidase activity. Selenium deficiency has been found in association with skeletal and cardiac myopathy and may increase the risk for cardiovascular diseases and for cancer. We studied 39 hemodialysis patients and 15 control subjects. Plasma selenium, plasma glutathione peroxidase activity and erythrocyte glutathione peroxidase activity were lower than in controls (38 +/- 14 vs. 88 +/- 17 micrograms/liter (P less than 0.01); 153 +/- 32 vs. 334 +/- 41 IU/liter (P less than 0.01), 19 +/- 4 vs. 26 +/- 4 IU/g Hb (P less than 0.01), respectively). Plasma selenium and plasma glutathione peroxidase activity were strongly correlated with duration of dialysis. There was no correlation between plasma selenium and protein or calorie intakes. Plasma selenium was lower in patients dialyzed with highly permeable membranes (P less than 0.01). The total muscle mass, assessed by anthropometry, was lower in the patients who had the lowest plasma selenium (P less than 0.01) and plasma glutathione peroxidase activity (P less than 0.05). Interventricular septum hypertrophy, documented by echocardiography, was greater in patients with the lowest plasma selenium and plasma glutathione peroxidase activity (P less than 0.01). Twenty hemodialysis patients had oral supplementation of 500 micrograms/day of sodium selenite for three months, and then, 200 micrograms/day for the next three months. Plasma selenium increased as early as the first week and reached a plateau similar to the control levels after three weeks. Plasma glutathione peroxidase activity increased after two months but remained below controls. Erythrocyte glutathione peroxidase activity reached a higher value than controls after one month.(ABSTRACT TRUNCATED AT 250 WORDS)

[Correction of selenium deficiency in patients with renal failure undergoing hemodialysis]. / Correction du déficit en sélénium chez des insuffisants rénaux hémodialysés.

Plasma selenium levels (p Se) as well as glutathione peroxidase activity in plasma (p GPx) and in erythrocytes (e GPx) were measured in 39 haemodialysis patients. Glutathione peroxidase is a selenium-dependent enzyme which protects cells against oxidation. The mean level values obtained were significantly lower in patients than in controls: p Se: 38 +/- 14 versus 88 +/- 17 micrograms/l; p GPx: 15 +/- 32 versus 334 +/- 41 IU/l; e GPx: 19 +/- 4 versus 26 +/- 4 IU/g Hb. These values were found to correlate significantly with the duration of dialysis and with the type of membrane utilized. The total muscular mass was significantly smaller in patients with the lowest p Se or p GPx values. At echocardiography, septal hypertrophy correlated with both p Se and p GPx. Twenty patients were supplemented with sodium selenite administered orally at the end of each haemodialysis session during 6 months. After this period, muscular mass and septal hypertrophy were decreased and the echocardiographic contractility parameters were improved, albeit not significantly.

Effects of nifedipine on cisplatinum-induced nephrotoxicity in rats.

The effects of calcium channel blockade with nifedipine (N) on cis-diammine dichloroplatinum II (CDDP)-induced nephrotoxicity were tested in male Sprague-Dawley rats. Renal function was evaluated before and five days after CDDP administration (5 mg/kg). The rats were treated with various doses of N (0.1; 0.3; 0.6 mg/kg/day) 2 days before CDDP administration and throughout the study. The severity of CDDP-induced acute renal failure was markedly modified in N-treated animals according to the daily dosage of N. At 0.3 and 0.6 mg/kg BW/day, N enhanced CDDP nephrotoxicity. Serum creatinine was 637 +/- 45 and 611 +/- 71 mumoles/liter, respectively, 5 days after CDDP administration (vs. 313 +/- 24 mumoles in animals treated with CDDP alone; p less than 0.05). In these animals the plasma potassium level was significantly elevated at day 7 when compared with CDDP-treated and control rats. In contrast, at the dose of 0.1 mg/kg BW/day N attenuated CDDP nephrotoxicity with a serum creatinine of 214 +/- 35 mumoles at the end of the study. The pathologic changes were also more severe in the groups receiving 0.3 and 0.6 mg/kg of nifedipine. We postulate that at the higher doses (0.3 and 0.6 mg/kg) the systemic hemodynamic effects of nifedipine may override the potentially beneficial intrarenal effect which may account for the favorable results recorded with a dosage of 0.1 mg/kg.

[Serum zinc and copper in hypercholesterolemia]. / Zinc et cuivre sériques dans l'hypercholestérolémie.

For some authors, absolute or relative copper deficiency, with an elevated plasmatic zinc/copper ratio, could be a risk factor in the etiology of cardiovascular diseases by altering lipid metabolism. Animal or human studies carried out with zinc and/or copper supplemented or deficient diets on biochemical lipid parameters, led to inconsistent results. Nevertheless, no study was already done in hypercholesterolemic patients, concerning possible correlation between serum levels of these trace elements and cholesterol, HDL cholesterol and apolipoprotein B blood levels. 67 patients were distributed in three groups according to their hypercholesterolemia. The serum copper concentration was elevated, serum zinc concentration and zinc/copper ratio were decreased in the hypercholesterolemic group (cholesterol greater than 7.7 mmol/l). Serum zinc, copper and zinc/copper ratio were significantly correlated with HDL cholesterol (respectively r = + 0.56 p less than 0.05, r = - 0.68 p less than 0.01, r = + 0.76 p less than 0.001).

[Progressive dialytic encephalopathy. Role of the aluminium and neurological study. One case (author's transl)]. / Encéphalopathie progressive des dialysés: rôle de l'aluminium et étude neuropathologique. Une observation.

Report a typical case of dialytic dementia in a patient treated with aluminium gels. The course was fatal in fifteen months duration. Before interruption of aluminium gel intake, the aluminium blood level measured by atomic absorption spectrography was at 1300 microgram/l (normal less than 40 microgram/l). Cerebral aluminium was studied by the method of Le Gendre and Alfrey. On the three studied specimens of gray matter including, the parieto rolandic cortex, the thalamus, the cerebellar cortex, the mean aluminium concentration was seven times higher than the witness. The optic and electronic microscopy study showed important accumulation of lipofuscin. No neurofibrillary degeneration was observed. In contrast to the intensity of the clinical signs and the fatal course the cerebral lesions were slight.

[Prolonged and reversible encephalopathy in a chronic haemodialysis patient. Probable responsibility of aluminium salts (author's transl)]. / Encéphalopathie prolongée et réversible chez un dialysé chronique. Responsabilité probable des sels d'aluminium.

A case of encephalopathy with elevation of plasma aluminium level in a patient treated by maintenance hemodialysis is reported. Clinical symptoms were made of moderate impairment of intellectual functions and of intermittent drowsiness. EEG after 3 minutes of hyperpnea evidenced bisynchronous anteriorly dominant intermittent delta waves. Plasma aluminium level, determined by atomic absorption spectrophotometry, was initially at 300 microgram/l (normal range greater than 40 microgram/l). After interruption of aluminium gels, clinical and EEG symptoms slowly subsided in 9 months, plasma aluminium level came down to 145 microgram/l. This picture of encephalopathy could preceede irreversible dialysis dementia in chronic dialysis patients.

[Neuropathologic and toxicologic study of 12 cases of bismuth encephalopathy]. / Etude neuropathologique et toxicologique de douze cas d'encéphalopathie bismuthique (EB).

Examination of twelve cases of bismuth encephalopathy showed a constantand marked elevation of the bismuth levels in autopsy cerebral tissue (ranging from 2-8 mg/kg to 25 mg/kg). These values were found to be much higher than the last-measured Bismuth venous blood values. In every case, periveinular lymphocytic infiltration and abundant intra-cytoplasmic lipofuscin were seen. The microanalysis with Castaing's electrode revealed the presence of focal areas of bismuth in the leptomeningeal spaces. The significance of the lesions is not fully established and it will undergo further investigations.