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We studied the cytotoxic effect of copper-oxidized LDL in human primary human umbilical vein endothelial cells (HUVEC) and the immortalized EA.hy 926 cell line. Copper oxidized LDL (50-200 microg apoB/ml) induced concentration-dependent apoptotic cell death in HUVEC but did not induce apoptosis in EA.hy 926 cells. Only necrotic EA.hy 926 cells were evidenced at all copper oxidized LDL concentrations (25-200 microg apoB/ml), oxidation states (lightly, moderately and extensively copper-oxidized LDL) and incubation periods (4, 8 and 20 h). The different mechanisms of cell death induced by copper-oxidized LDL in EA.hy 926 cells and HUVEC may be related to various factors such as cytokines. In this study, we investigated whether interleukin-8 may be implicated in this process. The interleukin-8 production was increased in EA.hy 926 cells but not in HUVEC incubated with oxidized LDL. This increase in EA.hy 926 cells was associated with necrosis but not apoptosis. Nevertheless, the addition of interleukin-8 to HUVEC did not inhibit apoptosis induced by oxidized LDL. As the lower antioxidant capacity of EA.hy 926 cells results in higher sensitivity to oxidized LDL cytotoxicity (as we previously described), the redox status of cells may also control the form of endothelial cell death. In atherosclerotic lesions, the formation of apoptotic endothelial cells may result in part from the induction by oxidized LDL.

Background: In France, several cases of vitamin D-deficiency rickets among adolescents have been reported, but no prophylaxis measure has been systematically recommended at this age. The aim of this study was to measure 25-hydroxyvitamin D (25-(OH)D) levels and to search for biological signs of vitamin D deficiency during adolescence. Moreover, the effects of a unique oral dose of 100,000 IU of vitamin D3, given during the winter, were analysed., Population and Methods: Circulating levels of 25-(OH)D, 1,25-dihydroxyvitamin D, intact parathyroid hormone (iPTH), alkaline phosphatase activities, calcium and phosphate were measured in 53 adolescents aged 10-17 years (81% of metropolitan origin), seen during the winter. The effect of a single oral dose of 100,000 IU of vitamin D3 or of placebo was studied in 15 of these subjects., Results: 24.5% of the adolescents had low 25-(OH)D concentrations (< 6 ng/ml), this frequency being even more elevated (38%) at the end of pubertal maturation (stages 4 and 5). An increase in iPTH concentrations was found in subjects with lowest 25-(OH)D levels (< 3 ng/ml). An oral dose of 100,000 IU of vitamin D3 resulted in a significant increase in the 25-(OH)D levels; yet, these levels remained within the normal range during the 1-2 month follow-up of the nine treated subjects. This dosage made it possible to correct the low calcium concentrations (2.20-2.24 mmol/l) found before treatment in three adolescents., Conclusions: The high frequency of low vitamin D status observed during puberty and its normalization after a 100,000 IU vitamin D3 supplementation show the interest and safety of this intermittent 100,000 IU vitamin D3 supplementation to adolescents during the winter season.

Recently, intravenous administration of low doses of magnesium has proved remarkably effective in the treatment of acquired torsade de pointe, but its electrophysiologic effects remain poorly understood. Three clinical cases are reported in three distinct situations (quinidine treatment, hypokalemia, bradycardia with complete atrioventricular block). These cases confirm the efficacy of magnesium, which acts without notable modification of ventricular cycles or the duration of repolarization. In ten patients undergoing intracavitary exploration, the electrophysiologic parameters were analyzed before and after injection of magnesium sulfate (35 mg/kg). Only three parameters were significantly altered; the corrected sinusal recovery time (increase from 245 +/- 92 ms to 296 +/- 96 ms), the effective nodal refractory period (increase from 333 +/- 98 ms to 346 +/- 93 ms), and the Wenckebache period (decrease from 157 +/- 28/min to 144 +/- 21/min). No changes were noted in other parameters, notably ventricular (QT interval, QRS duration, HV interval, and effective ventricular refractory period). The arrhythmic action on the ventricle is therefore remarkable and is not accompanied by patent electrophysiologic effects. The efficacy of magnesium in torsade de pointe may suggest action on calcium currents.

In cirrhotic, steatosic and healthy subjects, the authors studied the metabolism of disulfiram (TETD) administrated orally (500 mg) 3 consecutive days. Carbon disulfide (CS2) and the whole TETD, diethyl dithiocarbamate (DDC) disulfides, were determined by a gas chromatographic method. The evolution of metabolites is similar in steatosic and healthy subjects. In cirrhotics the CS2, DDC and disulfides level increase within the 3 days. This phenomenon may be related with hepatic toxicity of TETD and with the persistence of disulfiram-alcohol reaction. The authors suggest to use low doses of disulfiram in cirrhotic.

Twelve premature newborns mechanically ventilated with high FiO2 for hyaline membrane disease were tested for SOD contents during their first two weeks of life. CuSOD and MnSOD were measured in plasma, platelets and red cells using a radioimmunology method. No correlation was found between FiO2 levels neither with CuSOD and MnSOD contents. Furthermore no correlation was found between the SOD contents, at birth, and the constitution of bronchopulmonary dysplasia (BPD). Our results don't prove any relationship between lack of SOD and BPD. BPD pathogeny is certainly plurifactorial. Other protecting systems against O2 toxicity are also known to play an important role.

In cirrhotic patients, the authors studied the modification of the pharmacokinetics of ampicillin in the plasma and in the ascitic fluid, as well as its concentration in the urine. The influence of the jaundice, the ascites and diuretics were studied. In cirrhosis, dilution and elimination of the antibiotic are modified, as is shown by the increase in T 1/2 alpha and T 1/2 beta. These anomalies seem to be due essentially to modifications in the distribution volume; the degree of hepatocellular insufficiency does not appear to be of importance. The ascites acts as an independent compartment, into which the antibiotic's passage in slight. The practical consequences are the following: less frequent injections, increasing of the fractionated doses, in situ injections of ampicillin in cases of infection of the ascitic liquid.