ABSTRACT
To evaluate the hypothesis that platelet activating factor (PAF) antagonism may affect the functional recovery following the nerve injuries and also to evaluate the effect of PAF receptor antagonism on the neuroprotective effect of tacrolimus and sodium valproate, effect of PAF receptor antagonist, WEB2086 was evaluated in animal models of sciatic nerve crush and endothelin-1 induced focal cerebral ischemia. WEB2086, per se, while attenuating spontaneous sensory motor recovery after sciatic nerve crush, enhanced functional recovery after focal cerebral ischemia. WEB2086 also attenuated the neuroprotective effect of tacrolimus and sodium valproate subsequent to peripheral nerve injury, while it significantly improved the neuroprotective action of tacrolimus and sodium valproate following cerebral ischemia reperfusion injury. These results suggest that PAF receptor antagonists alone and in combination with tacrolimus/sodium valproate could be used in the treatment of cerebral ischemia reperfusion injuries however, their use following peripheral nerve injuries could be detrimental.
Subject(s)
Animals , Enzyme Inhibitors/pharmacology , Female , Histone Deacetylases/physiology , Ischemic Attack, Transient/rehabilitation , Male , Mice , Nerve Crush/rehabilitation , Neuroprotective Agents/metabolism , Phosphoric Monoester Hydrolases/antagonists & inhibitors , Platelet Activating Factor/antagonists & inhibitors , Sciatic Nerve/drug effectsABSTRACT
Axenically grown E. histolytica possess significant acid phosphatase activity. The Km of the enzyme was found to be 7.1 x 10(-3) and was maximally active at pH 4.5. Acid phosphatase activity was significantly inhibited by Cu2+, cysteine and was activated by tartrate and fluoride. It was found that E. histolytica acid phosphatase differs in some properties as compared to the enzyme reported from other sources.
Subject(s)
Animals , Copper/pharmacology , Cysteine/pharmacology , Entamoeba histolytica/enzymology , Enzyme Activation , Fluorides/pharmacology , Phosphoric Monoester Hydrolases/antagonists & inhibitors , Tartrates/pharmacologyABSTRACT
Se determinaron receptores estrogénicos testiculares en presencia de inhibidores de fosfatasas, molibdato (Mo04), wolframato (W04) y fluoruro (F-), bajo diferentes condiciones experimentales. A 0-4-C el Mo04 mimetizó parcialmente la acción estabilizadora del ditiotreitol (DTT) sobre la unión del estrógeno a su receptor citosólico, sugiriendo un efecto protector sobre los grupos sulfhidrilo reducidos. Por otra parte, a 25-C, en presencia de DTT, el efecto de Mo04 fue observado en homogenato y sobrenadante de baja velocidad, pero no se evidenció en citosol. Un posible mecanismo protector de la actividad de unión basado en la inhibición de la actividad de fosfatasas fue corroborado mediante el uso de W04. La actividad fosfatasa ácida resultó inhibida por estos agentes, mientras que la fosfatasa alcalina no presentó modificaciones. El agregado de Mo04 y W04, provocó, además, una inhibición siginificativa de la actividad proteolítica. Estos resultados sugieren que el Mo04 podría estabilizar la unión de estrógenos a sus receptores testiculares, a través de tres posibles mecanismos: 1) protección de grupos sulfhidrilo reducidos; 2) inhibición de la fosfatasa ácida y 3) inhibición de la actividad protelítica