Mechanisms by which epoxyeicosatrienoic acids (EETs) elicit cardioprotection in rat hearts.

Cytochrome P450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites, the epoxyeicosatrienoic acids (EETs), have been shown to produce reductions in infarct size in canine myocardium following ischemia-reperfusion injury via opening of either the sarcolemmal K(ATP) (sarcK(ATP)) or mitochondrial K(ATP) (mitoK(ATP)) channel. In the present study, we subjected intact rat hearts to 30 min of left coronary artery occlusion and 2 h of reperfusion followed by tetrazolium staining to determine infarct size as a percent of the area at risk (IS/AAR, %). The results demonstrate that the two major regioisomers of the CYP epoxygenase pathway, 11,12-EET (2.5 mg/kg, iv) and 14,15-EET (2.5 mg/kg, iv) significantly reduced myocardial infarct size (IS/AAR, %) in rats as compared with control (41.9+/-2.3%, 40.9+/-1.2% versus 61.5+/-1.6%, respectively), whereas, a third regioisomer, 8,9-EET (2.5 mg/kg, iv) had no effect (55.2+/-1.4). The protective effect of pretreatment with 11,12- and 14,15-EETs was completely abolished (61.9+/-0.7%, 58.6+/-3.1%, HMR; 63.3+/-1.2%, 63.2+/-2.5%, 5-HD) in the presence of the selective sarcK(ATP) channel antagonist, HMR 1098 (6 mg/kg, iv) or the selective mitoK(ATP) channel antagonist, 5-HD (10 mg/kg, iv) given 10 min after 11,12- or 14,15-EET administration but 5 min prior to index ischemia. Furthermore, concomitant pretreatment with 11,12- or 14,15-EET in combination with the free radical scavenger, 2-mercaptopropionyl glycine (2-MPG), at a dose (20 mg/kg, iv) that had no effect on IS/AAR (57.7+/-1.3%), completely abolished the cardioprotective effect of 11,12- and 14,15-EETs (58.2+/-1.6%, 61.4+/-1.0%), respectively. These data suggest that part of the cardioprotective effects of EETs in rat hearts against infarction is the result of an initial burst of reactive oxygen species (ROS) and subsequent activation of both the sarcK(ATP) and mitoK(ATP) channel.

Mutagenicity studies on tiopronin.

alpha-Mercaptopropionylglycine (tiopronin, Mucolysin), a drug endowed with an interesting mucolytic activity, was tested for mutagenicity by means of the following in vitro and in vivo tests: mutagenesis on S. typhimurium with and without metabolic activation, genetic mutation on S. pombe P1 with and without metabolic activation, gene conversion on S. cerevisiae D4 with and without metabolic activation, urinary assay in the mouse with S. cerevisiae D4, host mediated assay in the mouse with S. cerevisiae D4 and micronucleus test in the mouse. On the basis of the results obtained tiopronin proved to be free of mutagenic activity.

[A study on administration of antibiotics during operation for prevention of postoperative infections].

Two antibiotics, piperacillin (PIPC) and cefoperazone (CPZ) were administered during operation and determined of efficacy for prevention of postoperative infections. Following administration of PIPC and CPZ during operation, high serum concentrations were obtained. In exudates not so high concentrations were achieved with either PIPC or CPZ. This was considered to be probably due to the period and methods of collection of specimens used in this study. Bacteriological studies of washings of wounds obtained during operation gave negative results in all cases. It was considered that administration of antibiotics during operation may suffice for prevention of postoperative infections for all cases with relatively short operation time excepting for cases operated for malignant tumors or urinary tract lithiasis.

[Toxicological and radiobiological characteristics of meprin S-derivatives]. / Toksikologicheskaia i radiobiologicheskaia kharakteristika nekotorykh S-proizvodnykh méprina.

The effect was studied of synthetic thiosulfo- (TSPG), thiophospho- (TPPG), isothiuronium- (ITPG), and diethyldithiocarbamate (DDTKPG) alpha-mercaptopropionylglycine derivatives (alpha-MPG). Their toxicological and radiobiological characteristics were disclosed on mice exposed to gamma rays within a dose range of 9 to 11 Gy. TSPG in a dose of 3500 to 4500 mg/kg provided a 60 to 70% survival at LD100/10. In a dose of 4000 mg/kg the drug favoured a 70% protection of experimental animals when administered 4 hours before exposure to LD60/30. A high degree of protection (90%) was seen after TPPG preadministration (800 mg/kg) and exposure to LD100/10. DDTKPG (1300 mg/kg) also increased the survival of irradiated animals. No protective effect was observed after ITPG administration in doses of 50, 100, 180 and 360 mg/kg. Low toxicity and good enough antiradiation effect of the three compounds tested enabled the authors to proceed to more extensive studies.