Влияние N(фосфонометил)-глицина на фосфолиполитическую реакцию с участием фосфолипазы А2

The effect of N(phosphonomethyl)-glycine (glyphosate), the active ingredient of the «Squall» herbicide in a wide range of concentrations (1-1000 |ig/ml) on phospholipolysis catalyzed by pancreatic phospholipase A2 (PLA2, 3.1.1.4), under the conditions similar to digestion in the duodenum (pH 8.0, temperature S, micellar form PC), has been studied. It has been shown that a rapid method based on the use of in vitro phospholipolytic reaction as a simple model of the process of destruction of food and phospholipids of cell membranes, is promising for preliminary evaluation of the pesticide safety to humans and animals.Изучено влияние N(фосфонометил)-глицина (глифосата) - действующего вещества гербицида «Шквал» в широком диапазоне концентраций (1-1000 мкг/мл) на фосфолиполитическую реакцию, катализируемую панкреатической фосфолипазой А2 (ФЛА2, КФ 3.1.1.4), в условиях, близких к пищеварению в двенадцатиперстной кишке (рН 8,0, температура 37 °С, мицеллярная форма ФХ). Двумя независимыми методами, характеризующими накопление продуктов фосфолиполиза - лизофосфатилилхолина (с использованием ТСХ) и жирной кислоты (с регистрацией под ее действием спектральных изменений MetHb), установлено разнонаправленное действие глифосата на активность ФЛА2: в присутствии безопасных для человека и животных доз (до 100 мкг/мл) - активация в 1,4 раза, а под действием запредельных доз (до 1000 мкг/мл) - ингибирвание до 20% остаточной активности. Ингибиторная активность глифосата в концентрации 0,5 мМ при ферментативном гидролизе ФХ в мицеллярной фазе характеризуется величиной Кi равной 24 мМ, а ингибирование носит конкурентный характер. Показано, что экспресс-метод на основе использования in vitro фосфолиполитической реакции в качестве простой модели процесса разрушения фосфолипи-дов пищи и клеточных мембран перспективен в целях предварительной оценки безопасности пестицидов для человека и животных

Modelling Foreign Real Estate Investment: The Spanish Case

Foreign real estate investment, Housing investment bubble, Foreign direct investment,

Pharmacokinetics of paclitaxel-containing liposomes in rats

In animal models, liposomal formulations of paclitaxel possess lower toxicity and equal antitumor efficacy compared with the clinical formulation, Taxol. The goal of this study was to determine the formulation dependence of paclitaxel pharmacokinetics in rats, in order to test the hypothesis that altered biodistribution of paclitaxel modifies the exposure of critical normal tissues. Paclitaxel was administered intravenously in either multilamellar (MLV) liposomes composed of phosphatidylglycerol/phosphatidylcholine (L-pac) or in the Cremophor EL/ethanol vehicle used for the Taxol formulation (Cre-pac). The dose was 40 mg/kg, and the infusion time was 8 to 9 minutes. Animals were killed at various times, and pharmacokinetic parameters were determined from the blood and tissue distribution of paclitaxel. The area under the concentration vs time curve (AUC) for blood was similar for the 2 formulations (L-pac: 38.1±3.32 μg-h/mL; Cre-pac: 34.5±0.994 μg-h/mL), however, the AUC for various tissues was formulation-dependent. For bone marrow, skin, kidney, brain, adipose, and muscle tissue, the AUC was statistically higher for Cre-pac. For spleen, a tissue of the reticuloendothelial system that is important in the clearance of liposomes, the AUC was statistically higher for L-pac. Apparent tissue partition coefficients (Kp) also were calculated. For bone marrow, a tissue in which paclitaxel exerts significant toxicity, Kp was 5-fold greater for paclitaxel in Cre-pac. The data are consistent with paclitaxel release from circulating liposomes, but with efflux delayed sufficiently to retain drug to a greater extent in the central (blood) compartment and reduce penetration into peripheral tissues. These effects may contribute to the reduced toxicity of liposomal formulations of paclitaxel