Search

The present investigation was designed to investigate the effect of the diterpene ent-pimara-8(14),15-dien-19-oic acid (pimaradienoic acid, PA) on smooth muscle extracellular Ca2 influx. To this end, the effect of PA on phenylephrine- and KCl-induced increases in cytosolic calcium concentration ([Ca2]c), measured by the variation in the ratio of fluorescence intensities (R340/380 nm) of Fura-2, was analysed. Whether bolus injection of PA could induce hypotensive responses in conscious normotensive rats was also evaluated. PA inhibited the contraction induced by phenylephrine (0.03 or 10 μmol L−1) and KCl (30 or 90 mmol L−1) in endothelium-denuded rat aortic rings in a concentration dependent manner. Pre-treatment with PA (10, 100, 200 μmol L−1) attenuated the contraction induced by CaCl2 (0.5 nmol L−1 or 2.5 mmol L−1) in denuded rat aorta exposed to Ca2+free medium containing phenylephrine (0.1 μ mol L−1) or KCl (30 mmol L−1). Interestingly, the inhibitory effect displayed by PA on CaCl2-induced contraction was more pronounced when KCl was used as the stimulant. Phenylephrine- and KCl-induced increases in [Ca2]c were inhibited by PA. Similarly, verapamil, a Ca2+channel blocker, also inhibited the increase in [Ca2]c induced by either phenylephrine or KCl. Finally, bolus injection of PA (1–15 mg kg−1) produced a dose-dependent decrease in mean arterial pressure in conscious normotensive rats. The results provide the first direct evidence that PA reduces vascular contractility by reducing extracellular Ca2 influx through smooth muscle cellular membrane, a mechanism that could mediate the hypotensive response induced by this diterpene in normotensive rats. [ABSTRACT FROM AUTHOR]

Objectives: Praziquantel and albendazole are currently used for chemotherapeutic treatment of neurocysticercosis. Albendazole has been found to be more effective than praziquantel; however, it is well known that not all patients will show a complete resolution of cysts. Searching for more effective treatments, this study was designed to evaluate the effect of the combination of praziquantel and albendazole sulphoxide in a Taenia crassiceps in vitro model as well as the kind of interaction between both drugs.Methods: In order to determine the concentration that produced 50% effect (EC50), T. crassiceps cysts were incubated in culture medium containing praziquantel (0.005–0.04 μg/mL), albendazole sulphoxide (0.021–0.16 μg/mL) or the combination of praziquantel and albendazole sulphoxide in a fixed-dose ratio (1 : 1). The experimental concentration (EC50Exp) of the combination was determined from the concentration-response curve constructed from the combined drug treatment. Isobolographic analyses were used to define the nature of the interaction between praziquantel and albendazole sulphoxide. Morphological and ultrastuctural alterations after different treatments over the parasite tissue were observed by light and transmission electron microscopy.Results: The changes in ultrastructure were more marked with the praziquantel and albendazole sulphoxide combination. Also the cysticidal effect of the combination was observed earlier than that of each drug alone. When isobolographic analysis was employed, we found that the experimental EC50 value (0.042 μg/mL) was not significantly different from the theoretical EC50 value (0.035 μg/mL), which indicates an additive interaction between praziquantel and albendazole sulphoxide.Conclusions: Our study suggests that the combination of praziquantel and albendazole sulphoxide could potentially improve the current neurocysticercosis treatment. [ABSTRACT FROM AUTHOR]