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1.
Acta cient. venez ; 39(2): 140-6, 1988. ilus
Artigo em Inglês | LILACS | ID: lil-74771

RESUMO

Ketoconazole, a dioxolane imidazole, affects growth and sterol synthesis by Trypanosoma (Schizotryparum) cruzi epimastigotes in a time - and concentration - dependent manner. Starting with a cell density of 10 7 cells/ml, a 10 -4M concentration of the drug blocks instantaneously growth, but with 10 -5M and 10 -6M growth arrest takes place at 48 and 96 hours, respectively. A study of the sterol content of the parasites and their de novo synthesis reveals that the drug induces the accumulation of trimethyl- and, to a much lesser extent, dimethyl-sterols with a progressive decrease of ergosterol-like desmethyl-sterol pool. Sterols added to the growth medium can partially reverse the growth inhibitory effects of ketoconazole, ergosterol being much more effective that cholesterol in this action. These facts suggest an essential function performed in T cruzi by ergosterol, which cannot be replaced by cholesterol, a compound which is passively absorbed from the growth medium and remains in the drug-treated cells. At 10 -6M ketoconazole blocks completely the incorporation of 14C-acetate in desmethyl-sterols and >97% of the radioactivity appears in the trimethyl-sterol fraction at 24 hours; further incubation leads to the appearance of a slight amount of radioactivity in the dimethyl-sterol fraction (10% at 96 hours)..


Assuntos
Cetoconazol/farmacologia , Esteróis/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos
2.
s.l; s.n; s.f. 63 p. ilus, tab.
Tese em Espanhol | LILACS | ID: lil-121840

RESUMO

Se estudió el efecto del ketoconazol como un inhibidor de la reproducción in vitro de los epimastigotes del trypanosoma cruzi, determinando el volumen de restitución del crecimiento de los parásitos por ketoconazol al añadir esteroles exógenos al medio de cultivo, para ello utilizaron reactivos y soluciones. Mediante la inhibición del crecimiento producida por baja concentraciones de ketoconazol es mediada por la desaparición del ergosterol y esteroles similares de la membrana del parásito, los cuales parecen cumplir funciones esenciales que no pueden ser reemplazadas por colesterol. Los esteroles que se acumulan en las células tratadas, indican marcadas diferencias de este organismo como otros eucariotas inferiores, incluyendo leishmania mexicana, y son los responsables del aumento de la fluidez de la membrana de estos parásitos, con la consecuente alteración de otras propiedades tales como permeabilidad y aglutinación inducida por concanavalina-A


Assuntos
Doença de Chagas/patologia , Doença de Chagas/terapia , Técnicas In Vitro , Cetoconazol/farmacologia , Cetoconazol/uso terapêutico , Trypanosoma cruzi/parasitologia
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