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Biomedical subjects

M Hubert

Publications and source records attributed to M Hubert.

52 records · Page 3Linked to original sources
PubMedDate not supplied

Similarities and differences in mechanisms of cardiotoxins, melittin and other myotoxins.

Myonecrosis induced in vivo by cardiotoxin, melittin, and Asp49 and Lys49 phospholipase A2 (PLA2) myotoxins involves rapid lysis of the sarcolemma, myofibril clumping, and hypercontraction of sarcomeres. In contrast, skeletal muscle necrosis induced by crotamine and myotoxin a is much slower, consisting of mitochondrial and sarcoplasmic reticulum swelling, myofibril degeneration, and lack of sarcolemma or transverse tubule damage. The mechanisms contributing to the myonecrosis induced by these peptides were evaluated. Two cardiotoxins and two Lys49 PLA2 myotoxins lysed primary cultures of human skeletal muscle within 24 hr at a concentration of 0.25 microM, while melittin, crotamine, and myotoxin a, and an Asp49 PLA2 myotoxin were non-cytolytic at concentrations up to 5.0 microM, suggesting that cytolysis is not a good measure of myotoxicity. Crotamine and the Lys49 PLA2 myotoxin altered Ca2+ ion flux in human heavy sarcoplasmic reticulum by opening the ryanocine receptor. Whole-cell patch-clamp studies demonstrated that administrating crotamine intracellularly increased Na+ currents. Free fatty acids, liberated by activation of tissue phospholipase C or by the PLA2 activity of the myotoxins, were monitored for crotamine, myotoxin a and a Lys49 PLA2 myotoxin in cell cultures in which the lipids had been radiolabeled. Only the Lys49 myotoxin produced significant amounts of fatty acid in cell cultures, supporting a potential role for fatty acid production only in the mechanism of sarcolemma-destroying myotoxins. These findings, coupled with those in the literature, support a hypothesis in which the myotoxins and/or products of lipase activity (e.g. fatty acids) are acting at a site existing on both the Na+ channel and a protein involved in Ca2+ release and probably serving a modulatory function for ion regulation. Based on the similarities in mechanisms between the toxins and fatty acids, the most likely site would be a fatty acid binding site on the protein (either similar to that on fatty acid binding proteins, or an acylated cysteine residue) or in the membrane.

Bee Venoms↗
PubMedDate not supplied

[Hepatitis B vaccine: characterization of the polypeptides of hepatitis B surface antigen (author's transl)].

In order to realize a new kind of hepatitis B vaccine, the polypeptide components of the outer-coat of the hepatitis B virus have been studied. The characterization of the polypeptides of purified hepatitis B surface antigen (HBsAg) was performed by SDS-polyacrylamide gel electrophoresis. Seven polypeptides were observed, designated P1 to P7, according to their increasing molecular weight: P1 (MW = 24,000), P2 (MW = 32,500) and P6 (MW = 78,000) represented the major components. When the reducing action was increased and followed by alkylation and citraconylation, a single polypeptide of low MW (5,000 less than MW less than 10,000) was isolated from HBsAg.

Electrophoresis, Polyacrylamide Gel↗
PubMedDate not supplied

Evaluation of effects of terbinafine on single oral dose pharmacokinetics and anticoagulant actions of warfarin in healthy volunteers.

STUDY OBJECTIVE: To evaluate the potential effects of oral terbinafine, a new synthetic antifungal agent of the allylamine class, on the pharmacokinetics and pharmacodynamics of racemic warfarin. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SUBJECTS: Sixteen healthy men. INTERVENTIONS: Placebo or terbinafine 250 mg was administered once/day for 14 consecutive days, separated by a washout period lasting at least 2 weeks. A single oral dose of racemic warfarin 30 mg was coadministered with placebo or terbinafine on day 8 of each treatment period. Blood samples were collected for 168 hours after administration of warfarin to determine the drug's pharmacokinetics and anticoagulant effects. MEASUREMENTS AND MAIN RESULTS: No major differences were seen in the plasma concentration-time profiles of a single dose of warfarin administered with terbinafine or with placebo. CONCLUSIONS: Because of the lack of clinically significant interactions between terbinafine and warfarin during multiple-dose administration of terbinafine, no adjustment of warfarin dosage during concomitant therapy appears to be necessary.

Adult↗