DEFAR - Departamento de Farmácia

URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530

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Assunto: search.filters.subject.Drug resistance

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    Trypanosoma cruzi : induction of benznidazole resistance in vivo and its modulation by in vitro culturing and mice infection.
    (2008) Santos, Fabiane Matos dos; Caldas, Sérgio; Cáu, Stêfany Bruno de Assis; Crepalde, Geovam Pereira; Lana, Marta de; Coelho, George Luiz Lins Machado; Veloso, Vanja Maria; Bahia, Maria Terezinha
    Through a continuous in vivo drug pressure protocol, using mice as experimental model, we induced benznidazole resistance in Trypanosoma cruzi stocks. Full resistance was obtained for four out of five T. cruzi stocks analyzed. However, the number of benznidazole doses (40–180), as well as the time (4–18 months) necessary to induce resistance varied among the different T. cruzi stocks. The resistance phenotype remained stable after T. cruzi stocks has been maintained by 12 passages in mice (six months) and in acellular culture for the same time. However, the maintenance of resistant parasite for 12 months in acellular culture induces a reduction in its level of benznidazole resistance, while no alteration was detected in parasite maintained for the same time in mice. The data showed the stability of the resistance acquired by drug pressure, but suggest the possibility of reversible changes in the resistance levels after maintenance for long time in acellular culture.
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    Trypanosoma cruzi : acute and long-term infection in the vertebrate host can modify the response to benznidazole.
    (2008) Caldas, Sérgio; Santos, Fabiane Matos dos; Lana, Marta de; Diniz, Lívia de Figueiredo; Coelho, George Luiz Lins Machado; Veloso, Vanja Maria; Bahia, Maria Terezinha
    We analyzed the influence of Trypanosoma cruzi maintenance in different hosts (dog and mouse) on its susceptibility to benznidazole treatment. Five T. cruzi stocks were isolated from dogs inoculated with Be-62 or Be-78 strain (both sensitive to benznidazole) 2–10 years ago, and the benznidazole sensitivity was then determined using the mouse as experimental model. The different T. cruzi stocks obtained from long-term infected dogs showed 50–90% drug resistance right after isolation. However, maintenance of these T. cruzi stocks in mice, by successive blood passages (2.5 years), led to either a decrease or stability of the drug resistance pattern and an increase in parasite virulence. We also demonstrated the effectiveness of the induction of parasitemia reactivation by cyclophosphamide immunosuppression in the evaluation of the response to the specific drug treatment.