RESUMEN
Platelets are relatively short-lived, anucleated cells that are essential for proper hemostasis. The regulation of platelet survival in the circulation remains poorly understood. The process of platelet activation and senescence in vivo is associated with processes similar to those observed during apoptosis in nucleated cells, including loss of mitochondrial membrane potential, caspase activation, phosphatidylserine (PS) externalization, and cell shrinkage. ABT-737, a potent antagonist of Bcl-2, Bcl-X(L), and Bcl-w, induces apoptosis in nucleated cells dependent on these proteins for survival. In vivo, ABT-737 induces a reduction of circulating platelets that is maintained during drug therapy, followed by recovery to normal levels within several days after treatment cessation. Whole body scintography utilizing ([111])Indium-labeled platelets in dogs shows that ABT-737-induced platelet clearance is primarily mediated by the liver. In vitro, ABT-737 treatment leads to activation of key apoptotic processes including cytochrome c release, caspase-3 activation, and PS externalization in isolated platelets. Despite these changes, ABT-737 is ineffective in promoting platelet activation as measured by granule release markers and platelet aggregation. Taken together, these data suggest that ABT-737 induces an apoptosis-like response in platelets that is distinct from platelet activation and results in enhanced clearance in vivo by the reticuloendothelial system.
Asunto(s)
Plaquetas/citología , Plaquetas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Animales , Apoptosis/efectos de los fármacos , Compuestos de Bifenilo/farmacología , Plaquetas/efectos de los fármacos , Separación Celular , Supervivencia Celular/efectos de los fármacos , Gránulos Citoplasmáticos/metabolismo , Perros , Relación Dosis-Respuesta a Droga , Exocitosis/efectos de los fármacos , Citometría de Flujo , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Nitrofenoles/farmacología , Fosfatidilserinas/metabolismo , Piperazinas/farmacología , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas , Sulfonamidas/farmacologíaRESUMEN
Substantial mortality attributable to infection with Parelaphostrongylus tenuis was reported in 2 herds of blackbuck antelope (Antelope cervicapra) in southwestern Louisiana. Both herds had outbreaks in which all affected antelope had neurologic disease and subsequently died. Affected antelope were anorectic and weak. They staggered, trembled, isolated themselves from the herd, became recumbent, and, possibly, were blind. In 1 herd, 6 of 27 antelope were affected, and in the second herd, 7 antelope were affected. Both herds were on farms that raised various native and imported ruminants, including white-tailed deer. None of the remaining ruminants was affected during these outbreaks, and subsequent outbreaks have not been reported. Four antelope and the brain of a fifth antelope were submitted for postmortem examination. Meningeal worms were identified grossly in only 1 antelope. Metastrongyloid nematodes were detected histologically in 3 antelope. The amount and extent of inflammation varied greatly among affected antelope.