Oral glutamine dipeptide prevents against prolonged hypoglycemia induced by Detemir insulin in rats.

The role of glutamine dipeptide (GDP) to prevent against prolonged insulin induced hypoglycemia (IIH) in overnight fasted rats was investigated. The glycemia was measured 0, 2, 4, 8, and 10 h after an intraperitoneal (i.p.) injection (1 U/kg) of Detemir insulin. Because the lowest glycemia was obtained 4 h after insulin administration, the experiments were done at this time. The hypoglycemia obtained 4 h after insulin injection was partially prevented with increasing oral doses of GDP (1.56, 3.12, 6.25, 12.5 mg/kg). The best result was obtained with 12.5 mg/kg. However, from this dose (25.0, 50.0, 100.0 mg/kg), the values of glycemia progressively decreased (p<0.05). The effect of GDP to prevent prolonged IIH was mediated, partly at least, by an intensification of liver gluconeogenesis. Moreover, the increased portal availability of GDP, L-alanine and L-glutamine after GDP administration also contributed to the IIH prevention, since the rate of gluconeogenesis progressively augmented with the infusion of increasing concentrations of these substances. However, after getting the maximal value, the rate of liver gluconeogenesis decreased (p<0.05) if a more elevated concentration of L-alanine or L-glutamine was infused. On the other hand, the liver gluconeogenesis during the infusion of increasing concentrations of GDP was unchanged. Because, GDP did not directly inhibit liver gluconeogenesis, but an inhibition of this metabolic pathway was observed with low ammonia concentrations (from 0.062 mM) it is possible that the ammonia from the catabolism of GDP by extra hepatic tissues could inhibit liver gluconeogenesis. This mechanism could help to explain the lower glycemia obtained with more elevated doses of oral GDP.

Aspectos clínicos e farmacológicos da associação sinvastatina-ezetimiba / Clinical and pharmacological aspects of the combination of simvastatin and ezetimibe

O objetivo do tratamento de pacientes hipercolesterolemicos deve ser o de alcançar concentração sangüínea de colesterol e LDL próximos ao de pacientes normais. Uma série de estratégias terapêuticas tem sido usada para obter um adequado controle da hipercolesterolemia. Dentre elas, destaca-se o emprego da sinvastatina que inibe a síntese hepática de colesterol e o ezetimiba que inibe a absorção intestinal de colesterol. A ausência de um adequado controle da colesterolemia com sinvastatina ou ezetimiba isoladamente abre a possibilidade de associação destes fármacos. Assim, a associação de sinvastatina e ezetimiba reduz com mais efi ciência a concentração sangüínea de colesterol e LDL do que o emprego separado de cada um destes fármacos. Portanto, podemos concluir que esta associação constitui a melhor opção terapêutica para pacientes nos quais a estatina isoladamente não alcança perfi l lipídico satisfatório.

The goal of hypercholesterolemic patient treatment should be obtaining both LDL and cholesterol blood level concentrations close to those of normal individuals. A number of therapeutic strategies have been carried out in order to achieve hypercholesterolemia proper control. Simvastatin stands out by preventing cholesterol synthesis in the liver as Ezetimibe prevents intestinal cholesterol absorption. The lack of proper cholesterolemia control regarding the single use of Simvastatin and Ezetimibe enables the possibility of combining such drugs. Thus, the combination of Simvastatin and Ezetimibe remarkably decreases the concentrations of both cholesterol blood level and LDL. Therefore, we conclude that such combination represents the best therapeutic choice for patients who isolated estatine does not reach a proper lipid profile.