RESUMO
In severe cases of sporotrichosis, it is recommended to use amphotericin B deoxycholate (D-AMB) or its lipid formulations and/or in association with itraconazole (ITC). Our aim was to evaluate the antifungal efficacy of a poly-aggregated amphotericin B (P-AMB), a nonlipid formulation, compared with D-AMB on systemic sporotrichosis caused by Sporothrix brasiliensis. In vitro assays showed that Sporothrix schenckii sensu stricto and S. brasiliensis yeast clinical isolates were susceptible to low concentrations of P-AMB and D-AMB. Although P-AMB presented a higher minimal inhibitory concentration (MIC) compared to D-AMB, its cytotoxic effect on renal cells and erythrocytes was lower. For the in vivo assays, male BALB/c mice were intravenously infected with S. brasiliensis yeasts, and P-AMB or D-AMB was administered 3 days post-infection. The efficacy of five therapeutic regimens was tested: intravenous monotherapy with P-AMB or D-AMB, intravenous pulsed-therapy with P-AMB or D-AMB, and intravenous therapy with P-AMB, followed by oral ITC. These treatments increased murine survival and controlled the fungal burden in the liver, spleen, lungs, and kidneys. However, only D-AMB monotherapy or the pulsed-therapies with D-AMB or P-AMB led to 100% survival of the mice 45 days post-infection; only pulsed administration of D-AMB was able to control the fungal load in all organs 45 days post-infection. Accordingly, the histopathological findings showed reductions in the fungal burden and inflammatory reactions in these treatment regimens. Together, our results suggest that the P-AMB formulation could be considered as an alternative drug to D-AMB for treating disseminated sporotrichosis.
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Esporotricose/tratamento farmacológico , Anfotericina B/administração & dosagem , Anfotericina B/química , Anfotericina B/farmacologia , Animais , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Contagem de Colônia Microbiana , Ácido Desoxicólico/administração & dosagem , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacologia , Ácido Desoxicólico/uso terapêutico , Modelos Animais de Doenças , Combinação de Medicamentos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Sporothrix/efeitos dos fármacos , Sporothrix/crescimento & desenvolvimento , Esporotricose/mortalidade , Taxa de SobrevidaRESUMO
Phytase production by a thermophilic mould Sporotrichum thermophile Apinis was investigated in solid state fermentation (SSF) using sesame oil cake as the substrate. Scanning electron microscopy of the fermented sesame oil cake revealed a dense growth of the mould with abundant conidia. Glucose, ammonium sulphate and incubation period were identified as the most significant factors by Plackett-Burman design. The optimum values of the critical components determined by central composite design of response surface methodology for the maximum phytase production were glucose 3%, ammonium sulphate 0.5% and incubation period 120 h. An overall 2.6-fold improvement in phytase production was achieved due to optimization. Highest enzyme production (348.76 U/g DMR) was attained at a substrate bed depth of 1.5 cm in enamel coated metallic trays. The enzyme liberated inorganic phosphate from wheat flour and soymilk with concomitant dephytinization and liberation of soluble inorganic phosphate.
Assuntos
6-Fitase/metabolismo , Eliminação de Resíduos/métodos , Sporothrix/enzimologia , Biotecnologia/métodos , Fermentação , Cinética , Óleo de Gergelim/metabolismo , Sporothrix/crescimento & desenvolvimento , Especificidade por SubstratoRESUMO
Four antifungal agents, amphotericin B, SDZ 89-485, itraconazole, and terbinafine, were tested for efficacy in a murine model of systemic sporotrichosis. Survival in the groups treated with amphotericin B, SDZ 89-485, and itraconazole was significantly better than that of control infected mice. However, these agents did not wholly protect the infected mice, as tail and paw lesions, whole-body radiographs, and positive cultures from survivors showed evidence of dissemination. Terbinafine-treated mice had the same or poorer survival as control infected mice, despite documented drug absorption.
Assuntos
Antifúngicos/uso terapêutico , Esporotricose/tratamento farmacológico , Anfotericina B/uso terapêutico , Animais , Avaliação Pré-Clínica de Medicamentos , Itraconazol , Cetoconazol/análogos & derivados , Cetoconazol/uso terapêutico , Camundongos , Naftalenos/uso terapêutico , Sporothrix/efeitos dos fármacos , Sporothrix/crescimento & desenvolvimento , Terbinafina , Triazóis/uso terapêuticoRESUMO
In order to clarify the mechanism of action of topical thermotherapy on sporotrichosis, the effects of heat on Sporothrix schenckii in vitro and in vivo were investigated by observing the percentage germination and the ultrastructure. When the spores were heated to 42 degrees C, it took 10 hr with the conidia, 2 hr with the yeast-like cells and 1 hr with the spores in vivo to reduce the germination rates to 10%. The percentage germination curves were reduced slowly at first but later exponentially. Changes in the ultrastructure became evident in 2 hr with the yeast-like cells and in 8 hr with the conidia. The ribosome count declined and amorphous dense materials appeared in the cytoplasm and mitochondria. In vivo, the outstanding feature of the heated spores was the diversity of internal ultrastructural changes encountered and morphological changes. These were observed at 1 hr post treatment.
Assuntos
Temperatura Alta , Sporothrix/fisiologia , Microscopia Eletrônica , Organoides/ultraestrutura , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/ultraestrutura , Sporothrix/crescimento & desenvolvimento , Sporothrix/ultraestruturaRESUMO
A medium containing L-sorbose and sodium deoxycholate was devised which induces colonial growth of Phanaerochaete chrysosporium in the presence of a variety of supplements. The restricted size and heavy conidial production of the colonies permits high plating densities and the use of a replica-plating technique for copying the pattern of colony growth.
Assuntos
Basidiomycota/crescimento & desenvolvimento , Meios de Cultura , Basidiomycota/isolamento & purificação , Ácido Desoxicólico , Concentração de Íons de Hidrogênio , Sorbose , Esporos Fúngicos/crescimento & desenvolvimento , Sporothrix/crescimento & desenvolvimentoRESUMO
Cellulase production and growth of a strain of Sporotrichum thermophile were studied by using a mineral salts medium supplemented with yeast extract and insoluble cellulose. The effects of cultural conditions, such as pH, nitrogen source, substrate concentration, and temperature, were examined. Maximum production of C1 and CX cellulases occurred at 45 C in 2 to 4 days, in the presence of 1% Solka/Floc as substrate, when NaNO3 or urea used as sources of nitrogen. Under these conditions, cellulolytic activity of culture filtrates appeared to be similar to that reported for Trichoderma viride grown in a favorable environment. However, comparable yields of cellulase were produced by S. thermophile in less than one-quarter the time required by mesophilic fungi.