[Case of refractory cardiogenic shock due to venlafaxine overdose : illustration of the support with veno-arterial extracorporeal membrane oxygenation]. / Choc cardiogénique réfractaire lié à une intoxication volontaire en venlafaxine : illustration de l'intérêt de l'ECMO veino-artérielle.

Venlafaxine is a widely prescribed antidepressant drug acting as a reuptake inhibitor of serotonin and noradrenaline. An overdose of venlafaxine can cause cardiovascular toxicity and cardiogenic shock can occur. A 32-year-old man ingested 12g of sustained-release venlafaxine in a suicidal attempt and developed within 24h acute heart failure with refractory cardiogenic shock requiring support by ECMO. The blood toxicology showed persistence of high levels of venlafaxine at day 10. The patient fully recovered and showed normal cardiac function at 3-months follow-up.

La venlafaxine est un antidépresseur largement prescrit agissant comme inhibiteur de recapture de la sérotonine et de la noradrénaline. Un surdosage en venlafaxine peut engendrer une toxicité cardiovasculaire allant jusqu'à l'état de choc cardiogénique. Un homme de 32 ans a ingéré 12 g de venlafaxine sous une forme à libération prolongée dans une tentative de suicide et a développé en 24 heures une insuffisance cardiaque aiguë avec choc cardiogénique réfractaire nécessitant un support hémodynamique par ECMO. La toxicologie sanguine a montré la persistance de niveaux élevés de venlafaxine au jour 10. Le patient s'est ensuite complètement rétabli et présentait une fonction cardiaque normale 3 mois après l'épisode.

Isolation from pig liver microsomes, identification by tandem mass spectrometry and in vitro immunosuppressive activity of an SDZ-RAD 17,18,19,20,21,22-tris-epoxide.

Macrolide immunosuppressive drugs such as tacrolimus (FK506) and sirolimus (rapamycin) are compounds largely used in modern immunosuppressive therapy and considered as powerful immunosuppressive agents. Some of these molecules are still under clinical development as, for example, SDZ-RAD (40-O-(2-hydroxyethyl)rapamycin), an immunosuppressive drug closely related to rapamycin. SDZ-RAD has a molecular mass of 957.57 Da (C53H83NO14) and shares the same common intracellular receptor as tacrolimus, the FK-506 binding protein (FKBP-12). SDZ-RAD exerts its pharmacological effect by binding to a different effector protein, inhibits the S6p 70-kinase and interrupts a different signal transduction pathway than tacrolimus. Both SDZ-RAD and rapamycin are metabolized mainly by the cytochrome P-450 3A4-dependent mixed function oxygenase enzyme system to hydroxylated and demethylated metabolites. We describe here the isolation from pig liver microsomes of a novel SDZ-RAD metabolite identified by electrospray tandam mass spectrometry as a new SDZ-RAD 17,18,19,20,21,22-tris-epoxide metabolite. The in vitro immunosuppressive activity as measured by the mixed lymphocyte reaction is more or less comparable to that of SDZ-RAD, although its pharmacological mode of action may be different from that classically described for rapamycin.

Isolation from rat urine and human liver microsomes and identification by electrospray and nanospray tandem mass spectrometry of new malagashanine metabolites.

Malagashanine has been isolated from indigenous madagascan Strychnos myrtoides alkaloids used traditionally to treat malaria. This alkaloid was found to enhance the action of chloroquine against chloroquine-resistant strains of Plasmodium falciparum when combined with classical antimalarial drugs (chloroquine, quinine). The present study was carried out in order to investigate by electrospray mass and tandem mass spectrometry and NMR spectroscopy the structure of two new metabolites isolated from rat urine and human liver microsomes. We were able to demonstrate the presence of two new metabolites of malagashanine corresponding to a malagashanine N-demethylated metabolite and to the oxidation of malagashanine in the alpha-position of the N-methyl group to produce a carbinolamine function. The latter metabolite may be subject to ring and open-chain tautomerism effects and dimeric species were detected in the electrospray mass spectrum.

The effect of intravenous administration of WEB 2086 on PAF-induced platelet aggregation in healthy Friesian calves.

The in vivo ability of the specific PAF-antagonist WEB 2086, a thienotriazolodiazepine, to inhibit platelet-activating factor (PAF) in cattle was investigated by in vitro determination of platelet aggregation curves. WEB 2086 was infused intravenously into a group of 5 healthy male Friesian calves in a dose of 3 mg/kg over 1 min. The resultant inhibition peaked between 30 min and 1 h after administration of WEB 2086. The inhibition was significantly reduced after 3 h and became non-significant after 6 h, but maximal pre-treatment aggregation had not been restored by 24 h after the injection of WEB 2086. These results confirm previous results obtained in vitro and suggest that WEB 2086 is a potent antagonist of PAF activity in calves. They also suggest that further clinical studies with WEB 2086 in cattle are desirable.

[The physician faced with an iodine deficiency: individual management of a public health problem]. / Le praticien face à la carence iodée: prise en charge individuelle d'un problème de santé publique.

Urinary iodine was measured in samples collected during the first week of life in newborns from the areas of Liège in Belgium and Cluj in Romania. In Liège, severe iodine deficiency was seen in 1 out of 8 newborns and mild iodine deficiency in 1 out of 3. A greater proportion of newborns showed iodine deficiency in Cluj. Since public health measures to prevent iodine deficiency have not been set up yet by belgian authorities, the practitioner has to ensure individually optimal iodine intake, particularly in pregnant women, in newborns and during infancy.

["CAPCIL". Posologic adjustment of aminoglycoside treatments]. / "CAPCIL". Adaptation posologique des traitements par aminoglycosides.

The objectives of the therapeutic drug monitoring are to assume the efficacy and inocuity of a medical treatment and the patient's observance. The administration of a drug to a patient is not always performed in the same conditions and therefore treatment has to be adapted. When necessary, this one is very often based on empiric or very approximative notions and, more seldom, on results of plasmatic concentrations of the drug. The CAPCIL program allows the possibility to objectivate the medical decision and adapt the posology on the basis of two kinetic parameters: the biological half-life and the distribution volume. Indeed, most of pharmacokinetics modifications (drug interactions, diseases, ...) are affecting the two parameters. With basic informations so as height and weight, posology, treatment objectives and peak/trough plasmatic concentrations of the drug, the program is proposing several posology adaptation schemes. The example of a once-a-day administration of amikacin is discussed.

[Plasma concentrations of vitamin K1 and acenocoumarol related to international normalized ratios]. / Concentrations plasmatiques de la vitamine K1 et de l'acenocoumarol en fonction du temps de quick (I.N.R.).

Reduced vitamins K are acting as cofactors of glutamic carboxylation of procoagulant factors (II, VII, IX and X). The reduction of these vitamins is inhibited by oral anticoagulants. The response to antivitamins K is individual and may change during the treatment of a patient. The determinations of plasmatic vitamin K and acenocoumarol may help to explain the mechanism of a resistance to the anticoagulant therapy. Quantifications of vitamin K1 are realized after liquid-liquid extraction with liquid chromatography and fluorescence detection after post-column reduction. For acenocoumarol, plasma concentration is measured, after liquid-liquid extraction, by liquid chromatograph, with ion trap mass spectrometer detector.