| Revista: | Memorias do Instituto Oswaldo Cruz |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000349504 |
| ISSN: | 0074-0276 |
| Autores: | Guerra, Caroline Rezende1 Ishida, Kelly1 Nucci, Marcio2 Rozental, Sonia2 |
| Instituciones: | 1Instituto de Biofisica Carlos Chagas Filho, Laboratorio de Biologia Celular de Fungos, Rio de Janeiro. Brasil 2Universidade Federal do Rio de Janeiro, Hospital Universitario Clementino Fraga Filho, Rio de Janeiro. Brasil |
| Año: | 2012 |
| Periodo: | Ago |
| Volumen: | 107 |
| Número: | 5 |
| Paginación: | 582-590 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Experimental |
| Resumen en inglés | Cryptococcus neoformans is an encapsulated fungus that causes cryptococcosis. Central nervous system infection is the most common clinical presentation followed by pulmonary, skin and eye manifestations. Cryptococcosis is primarily treated with amphotericin B (AMB), fluconazole (FLC) and itraconazole (ITC). In the present work, we evaluated the in vitro effect of terbinafine (TRB), an antifungal not commonly used to treat cryptococcosis. We specifically examined the effects of TRB, either alone or in conjunction with AMB, FLC and ITC, on clinical C. neoformans isolates, including some isolates resistant to AMB and ITC. Broth microdilution assays showed that TRB was the most effective drug in vitro. Antifungal combinations demonstrated synergism of TRB with AMB, FLC and ITC. The drug concentrations used for the combination formulations were as much as 32 and 16-fold lower than the minimum inhibitory concentration (MIC) values of FLC and AMB alone, respectively. In addition, calcofluor white staining revealed the presence of true septa in hyphae structures that were generated after drug treatment. Ultrastructural analyses demonstrated several alterations in response to drug treatment, such as cell wall alterations, plasma membrane detachment, presence of several cytoplasmic vacuoles and mitochondrial swelling. Therefore, we believe that the use of TRB alone or in combination with AMB and azoles should be explored as an alternative treatment for cryptococcosis patients who do not respond to standard therapies |
| Disciplinas: | Química, Biología |
| Palabras clave: | Bioquímica, Química farmacéutica, Hongos, Cryptococcus neoformans, Terbinafina, Morfogénesis fúngica, Diferenciación celular |
| Keyword: | Chemistry, Biology, Biochemistry, Medicinal chemistry, Fungi, Cryptococcus neoformans, Terbinafine, Fungal morphogenesis, Cell differentiation |
| Texto completo: | Texto completo (Ver PDF) |
