Familial isolated vitamin E deficiency. Extensive study of a large family with a 5-year therapeutic follow-up.

A major neurological deterioration, beginning with ataxia, led to the diagnosis of familial vitamin E deficiency in a girl. Based upon vitamin E determinations, 4/8 members of the (consanguineous) sibship were considered to be homozygous. Homozygosity was also found for the alleles of six markers linked to the AVED locus, recently identified in similar Tunisian or Sicilian families on chromosome 8q. Measures of vitamin E in lipoprotein fractions and in liver biopsy after vitamin E oral load suggested that free diffusion of vitamin E between the different compartments was possible and even increased. However, a high-affinity ligand seemed to be lacking, either in the hepatic recycling of vitamin E or in both the hepatic and the other vitamin E compartments. The 5-year substitutive treatment was successful only in the pre- or paucisymptomatic patients. Serum vitamin E must be measured in any unexplained progressive ataxia.

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)

Distribution of thiobarbituric acid-reactive substances in lipoproteins and proteins in serum.

We assessed the distribution of malondialdehyde (MDA) in lipoproteins and proteins in serum after using two procedures to separate the lipoproteins: sequential ultracentrifugation or selective precipitation with a sodium phosphotungstate and magnesium chloride reagent followed by ultracentrifugation of the supernate. MDA concentrations were determined by the thiobarbituric acid reaction and quantified by fluorometry. We found that 43% of the thiobarbituric acid-reactive substances (TBARS) was bound to the lipoproteins--27% to very-low- and low-density lipoproteins (VLDL-LDL) and 16% to high-density lipoproteins (HDL)--and from 11.5% to 15.8% to proteins, depending on the separation procedure. Residual unbound TBARS were located in the ultracentrifugation layers that contained no lipoproteins or proteins. The TBARS concentration in serum lipoproteins containing apolipoprotein B (i.e., VLDL-LDL) was the same after ultracentrifugation or selective precipitation. We therefore consider the precipitation method more suitable for routine TBARS determination in these lipoproteins, because it is easier to handle and faster. However, for determination of TBARS in HDL, selective precipitation requires subsequent ultracentrifugation at a density of 1.21 kg/L.

[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.

[Role of lipid peroxidation in the formation of atheroma]. / Rôle de la peroxydation lipidique dans la constitution de la plaque d'athérome.

The demonstration that lipid peroxidation (enzymatic or non enzymatic oxidation of polyunsaturated fatty acids) is involved and plays a pathophysiological role (in relation to the metabolic pathways of prostaglandins, leukotrienes and to others inflammation-related events) in the initiation of arteriosclerotic plaques is a breakthrough in the pathogenesis of atheroma. Macrophages play a central role in this mechanism. Indeed foam cells are macrophages loaded with oxidized low density lipoproteins (LDL). These oxidized LDL are preferentially recognized by macrophages thanks to their scavenger receptor. The role of such foam cells in the initiation and development of atheroma is well known. The formation of arteriosclerotic plaques results in important endothelial alterations, and endothelial cells lose their protective ability to prevent platelet aggregation and related thrombotic events. Inflammation and thrombosis are overlapping phenomena which are mediated by common cells (platelets, polymorphonuclear leucocytes, monocytes, macrophages, endothelial cells). During the activation of such inflammatory cells a number of eicosanoids are produced, and the profile of such metabolites is largely controlled by cellular interactions. In addition these inflammatory cells have the ability to produce oxygen free radicals, and initiate non enzymatic lipid peroxidation.