[Determination of serum or plasma alpha-tocopherol by high performance liquid chromatography: optimization of operative models]. / Dosage de l'alpha-tocophérol sérique ou plasmatique par chromatographie liquide haute performance: optimisation du mode opératoire.

A previous multicentric study set up by the Société française de biologie clinique has emphasized the usefulness of a standardized procedure for the determination by high performance liquid chromatography of alpha-tocopherol in serum or plasma. In our study, we have tested every step of the different published procedures: internal standard adduct, lipoprotein denaturation and vitamin extraction. Reproducibility of results was improved by the use of tocol as an internal standard when compared to retinol or alpha-tocopherol acetates. Lipoprotein denaturation was more efficient with ethanol addition than with methanol and when the ethanol/water ratio was > or = 0.7. Use of n-hexane or n-heptane gave the same recovery of alpha-tocopherol. When organic solvent/water ratio was > or = 1, n-hexane enabled to efficiently extract, in a one-step procedure, the alpha-tocopherol from both normo and hyperlipidemic sera. Performances of the selected procedure were: detection limit: 0.5 microM--linear range: 750 microM--within run coefficient of variation: 2.03%--day to day: 4.76%. Finally, this pluricentric study allows us to propose an optimised procedure for the determination of alpha-tocopherol in serum or plasma.

[Updating of relative data on tocopherols in clinical biochemistry]. / Actualisation des données relatives aux tocophérols en biochimie clinique.

The working group on lipophilic vitamins of the FSBC has reviewed current knowledge in the field of tocopherols and tried to summarize the most important and recent aspects that may be useful to clinical practitioners. The molecular structure of tocopherols and tocotrienols, their biogenesis, their analysis in foods, their metabolism in humans, their measurement in biological fluids, and the organism's needs and dietary requirements are reviewed. Their main functions as antioxidants and free radical scavengers are described at the molecular, ultra-structural, cellular and organ levels. The interest of these vitamins in three pathologies in which oxidative-stress has been implicated (atherosclerosis, cancer, kidney failure) is discussed.

Influence of heavy metals on the resistance of mice toward infection.

Previous studies have shown that heavy metals may exert marked immunomodulatory effects, at least in rodents, despite some discrepancies. However, the mechanism of their influence on the immune system is still unclear. As host resistance assays against experimental infections are generally considered as the most relevant criteria when predicting the immunotoxicity of drugs and chemicals, the effects of lead acetate, nickel chloride and sodium selenite on the resistance toward experimental Klebsiella pneumoniae infection was investigated in mice, with particular emphasis on the interference of the time of toxic exposure with the infectious challenge. Interestingly, one single intraperitoneal dose of 24 mg/kg lead or 4 mg/kg nickel enhanced the resistance of mice against Klebsiella pneumoniae when administered 24 hours before the infectious challenge, whereas host resistance proved to be impaired when the same dose was injected 5 hours after the infectious challenge. A 3-day pretreatment with 8 or 12 mg/kg lead also enhanced the resistance of mice but decreased it with 0.5 or 1 mg/kg nickel. In all cases, sodium selenite increased the resistance of mice toward infection. As lead, nickel and selenium appear to exert complex and possibly opposite effects on antibody response and phagocytosis, it remains to establish which immunotoxic consequences if any, an acute or chronic exposure to these heavy metals is likely to have in man.

Effects of josamycin on polymorphonuclear leucocyte chemotaxis.

The effects of josamycin on the chemotactic response of blood polymorphonuclear leucocytes were studied. After oral administration of 2 g/day or 50 mg/kg/day for five days in man and rats respectively, polymorphonuclear chemotaxis was reduced by 20%. After in-vitro incubation with 10 mg/l josamycin chemotaxis was unaltered, whereas a 15% decrease was noted with 25 mg/l josamycin. These data suggest that josamycin is unlikely to severely impair chemotaxis in patients.

Effects of erythromycin, josamycin and spiramycin on rat polymorphonuclear leukocyte chemotaxis.

The effects of three macrolide antibiotics were studied on rat polymorphonuclear leukocyte chemotaxis. Rats were given 25 mg/kg twice a day of either erythromycin, josamycin or spiramycin by gastric intubation for 5 days. In all cases, chemotaxis was found to be impaired by 10-20% only. As macrolides are known to reach high intracellular concentrations within polymorphonuclear leukocytes, our results suggest that these antibiotics are unlikely to exert a deleterious influence on the chemotactic response of treated patients.

Influence of lead acetate on hypersensitivity. Experimental study.

Recent studies showed that lead acetate has an important immunotoxicity for the phagocytic activity as well as humoral and cell-mediated immunity. We studied the influence of lead acetate on immediate and delayed hypersensitivity. The lead acetate exerts an important action on hypersensitivity reactions whether on rat mast cells degranulation (immediate hypersensitivity) or on contact hypersensitivity.

Assessment of the allergenic potential of althesin and its constituents.

The pharmaceutical formulation of Althesin was shown to have a weak allergenic potential in the guinea pig maximization test. Alphadolone and alphaxalone acetate were found to be devoid of such potential, while the status of Cremophor EL remained equivocal.