Effect of an antihypertensive hydrazine derivative on Ca2+ current of single frog cardiac cells.

The effects of MP 518, an acylated 2-chlorobenzylidene hydrazidone derivative with antihypertensive properties were investigated on the Ca current, ICa, recorded under whole-cell patch-clamp in single frog ventricular cells. MP 518 (1-100 microM) had no effect on ICa under control conditions. However, at 10 microM it significantly increased the beta-adrenergic stimulated ICa, an effect similar to that of isobutylmethyl-xanthine (IBMX), a non-specific phosphodiesterase inhibitor. The effects of MP 518 and IBMX were not, however, additive. This positive effect was also observed with both compounds, MP 518 and IMBX, when a submaximal dose of cyclic AMP was intracellularly perfused. In the presence of IBMX or at a high concentration (100 microM), MP 518 had a negative effect on beta-adrenergic stimulated ICa. It was thus considered that the main effect of MP 518 is an antiphosphodiesterase activity, since the increase in ICa induced by low concentrations of MP 518 could be related to inhibition of cAMP degradation; however, at higher concentrations, MP 518 antagonizes beta-adrenergic stimulation, possibly at several levels. Such an antiphosphodiesterase activity can account for the vasorelaxant effects as well as the tachycardic effects of MP 518.

[Not Available]. / Dosage protometrique des hydrogenes mobiles a l'aide de l'amidure de sodium.

Sodium amide is decomposed by compounds containing active hydrogen, with stoichiometric release of ammonia, which can be determined by titration with add. The proposed technique has been applied to representatives of various types of compound.

Fibroblast cultures in experimental disturbed metabolic conditions. effects of anti-inflammatory drugs.

Fibroblasts in normal metabolic conditions constitute a simple cellular model for the study of anti-inflammatory drugs in culture, but do not take into account the factors related to the acute inflammatory reaction. A new approach was tried in submitting the fibroblasts to the action of a mouse peritoneal exudate or selected activated macrophages. Disrupted peritoneal material was inoculated to cultures in a volume representing a number of cells corresponding to 25 or 50% of fibroblast concentration at day 0 of the experimental time. Three anti-inflammatory drugs were retained to study their effects on proliferation and metabolic parameters: hydrocortisone, indomethacin and a newly-described molecule, the methoxybenzalthiosemicarbazone (MBT). At day 0, 1, and 2, fibroblasts were counted and total cellular protein and cellular glycolytic activity were determined. 4.5 X 10(-5) M hydrocortisone and MBT protected the fibroblast from the antiproliferative action of peritoneal exudate whereas in experiments using activated macrophage homogenate, all drugs exerted a protective and stimulatory effect.

Passage of allophanoyl-gamma-lactones through the kidney.

In order to establish if allophanoyl-gamma lactones (B compounds) can pass through the kidney or if only the corresponding delta-hydroxybarbiturates (A compounds), formed by intramolecular alcoholysis, are able to do so, nine experiments were performed to study the urinary excretion of four different allophanoyl gamma-lactones B after administration to dogs. Excreted compounds were extracted, identified and quantised. From the amounts of unmodified administered lactones that were recovered, it is concluded that B compounds can pass through the kidney before isomerisation into the corresponding barbiturates A.

[Usual values of serum vitamin A using a modified fluorimetric method]. / Valeurs usuelles de la vitamine A sérique par une méthode fluorimétrique modifiée.

We report a fluorimetric technique for the determination of serum vitamin A. The critical study of this micromethod included trials of repeatability, inter-series reproducibility and an evaluation of its accuracy. It was compared with a method using high performance liquid chromatography followed by detection with UV spectrophotometry. Normal values were established for adults. The variations according to age were determined for children between the ages of 10 months and 15 years.

[Synthesis of potential metabolites of a barbiturate containing two branched side chains]. / Synthèse des métabolites potentiels d'un barbiturique porteur de deux chaînes ramifiées.

The two branched side chains of 5-(3-methylbutyl)-5-(2-methylpropyl)-barbituric acid present a tertiary carbon atom, which can be oxidized in vivo by hepatic enzymes. Potential metabolites of this compound are synthesised: the gamma-hydroxy metabolite can be oxidized directly by CrO3 while the beta-hydroxy metabolite can only be prepared by hydration of a double bond. This beta-hydroxybarbiturate then undergoes an alcoholysis leading to an allophanyl-gamma-lactone, which is hydrolysed into a carboxylic lactone, which can give a lactone by decarboxylation. On the other hand, a beta-gamma-dihydroxymetabolite is synthesised by double hydration of two double bonds using two different methods. A spirobilactone can also be synthesised from this dihydroxy compound.