Antifungal activity of liriodenine on agents of systemic mycoses, with emphasis on the genus Paracoccidioides

Endemic systemic mycoses remain a health challenge, since these opportunistic diseases are increasingly infecting immunosuppressed patients. The simultaneous use of antifungal compounds and other drugs to treat infectious or non-infectious diseases has led to several interactions and undesirable effects. Thus, new antifungal compounds should be investigated. The present study aimed to evaluate the activity of liriodenine extracted from Annona macroprophyllata on agents of systemic mycoses, with emphasis on the genus Paracoccidioides. Methods: The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined by the microdilution method. The cellular alterations caused by liriodenine on a standard P. brasiliensis (Pb18) strain were evaluated by transmission and scanning electron microscopy. Results: Liriodenine was effective only in 3 of the 8 strains of the genus Paracoccidioides and in the Histoplasma capsulatum strain, in a very low concentration (MIC of 1.95 µg.mL-1); on yeasts of Candida spp. (MIC of 125 to 250 µg.mL-1), including C. krusei (250 µg.mL-1), which has intrinsic resistance to fluconazole; and in Cryptococcus neoformans and Cryptococcus gattii (MIC of 62.5 µg.mL-1). However, liriodenine was not effective against Aspergillus fumigatus at the studied concentrations. Liriodenine exhibited fungicidal activity against all standard strains and clinical isolates that showed to be susceptible by in vitro tests. Electron microscopy revealed cytoplasmic alterations and damage to the cell wall of P. brasiliensis (Pb18). Conclusion: Our results indicate that liriodenine is a promising fungicidal compound that should undergo further investigation with some chemical modifications.(AU)

Antifungal activity of liriodenine on agents of systemic mycoses, with emphasis on the genus Paracoccidioides

Endemic systemic mycoses remain a health challenge, since these opportunistic diseases are increasingly infecting immunosuppressed patients. The simultaneous use of antifungal compounds and other drugs to treat infectious or non-infectious diseases has led to several interactions and undesirable effects. Thus, new antifungal compounds should be investigated. The present study aimed to evaluate the activity of liriodenine extracted from Annona macroprophyllata on agents of systemic mycoses, with emphasis on the genus Paracoccidioides. Methods: The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined by the microdilution method. The cellular alterations caused by liriodenine on a standard P. brasiliensis (Pb18) strain were evaluated by transmission and scanning electron microscopy. Results: Liriodenine was effective only in 3 of the 8 strains of the genus Paracoccidioides and in the Histoplasma capsulatum strain, in a very low concentration (MIC of 1.95 µg.mL-1); on yeasts of Candida spp. (MIC of 125 to 250 µg.mL-1), including C. krusei (250 µg.mL-1), which has intrinsic resistance to fluconazole; and in Cryptococcus neoformans and Cryptococcus gattii (MIC of 62.5 µg.mL-1). However, liriodenine was not effective against Aspergillus fumigatus at the studied concentrations. Liriodenine exhibited fungicidal activity against all standard strains and clinical isolates that showed to be susceptible by in vitro tests. Electron microscopy revealed cytoplasmic alterations and damage to the cell wall of P. brasiliensis (Pb18). Conclusion: Our results indicate that liriodenine is a promising fungicidal compound that should undergo further investigation with some chemical modifications.(AU)

Paracoccidioidomycosis in southern Rio Grande do Sul: a retrospective study of histopathologically diagnosed cases

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis and is endemic to Brazil. The aim of this study was to perform a retrospective analysis of the PCM cases in the countryside south of Rio Grande do Sul, Brazil. The files from four histopathology laboratories located in the city of Pelotas were obtained, and all of the epidemiological and clinical data from the PCM diagnosed cases were collected for analysis. A total of 123 PCM cases diagnosed between 1966 and 2009 were selected. Of these patients, 104 (84.5%) were male, and 17 were female. The patients ranged from 02 to 92 years of age. Fifty-two cases (41.9%) were obtained from the oral pathology laboratory, and the remaining 71 cases (58.1%) were obtained from the three general pathology laboratories. Of all of the patients studied, 65.2% lived in rural zones and worked in agriculture or other related fields. Data on the evolution of this disease was available for 43 cases, and the time frame ranged from 20 to 2920 days (mean = 572.3 days). An accurate diagnosis performed in less than 30 days only occurred in 21% of the cases. PCM is endemic to the countryside of Rio Grande do Sul. Therefore, it is recommended that PCM be included as a differential diagnosis, mainly for individuals between 30 and 60 years of age, living in rural zones and who have respiratory signs and associated-oropharyngeal lesions.(AU)

Isolamento ambiental e caracterização bioquímica de Cryptococcus

A criptococose é uma infecção fúngica causada por levedura do gênero Cryptococcus. Dentre as principais micoses sistêmicas nas últimas décadas, a criptococose vem assumindo um relevante papel, com altos índices de morbidade e mortalidade principalmente em pacientes imunodeprimidos. O presente trabalho teve por objetivo verificar a ocorrência de Cryptococcus spp. em amostras ambientais na área urbana de Bauru-SP, Brasil, estabelecendo os focos ambientais, com a finalidade de compreender a eco -epidemiologia do microrganismo. Cinquenta amostras ambientais de dez locais representativos foram processadas e semeadas em ágar semente de Níger (NSA) e Sabouraud. As colônias com características macro e micromorfológicas compatíveis com Cryptococcus foram submetidas a provas bioquímicas, sendo que 12/50 (24%) das amostras foram positivas para o gênero Cryptococcus. A partir dos resultados obtidos, pode-se concluir que foram encontradas espécies causadoras de criptococose no município de Bauru, constituindo-se na existência de focos ambientais, com potencial patogênico para o homem e animais. A compreensão da eco-epidemiologia do Cryptococcus constitui em uma importante ferramenta na estratégia de medidas preventivas.

Cryptococcosis is a fungal infection caused by yeasts of the genus Cryptococcus. One of the main systemic mycoses in recent decades, has been assuming an important role, with high rates of morbidity and mortality especially in immunosuppressed patients. The present study aimed to verify the existence of Cryptococcus spp. from environmental samples in the urban area of Bauru-SP, Brazil, establishing the environmental focus, with the purpose of understand the eco-epidemiology of the micro-organism. Fifty environmental samples from ten representative sites were processed and seeded in agar Niger seed (NSA) and Sabouraud. The colonies with macro and micromorphological compatible with Cryptococcus underwent biochemical tests, and 12/50 (24%) of the samples were positive for the genus Cryptococcus. From the results obtained, it can be concluded that species that cause cryptococcosis were found in the city of Bauru-SP, Brazil, constituting the existence of outbreaks with potential environmental pathogenic for human and animals. The eco-epidemiological understanding of the Cryptococcus constitutes an important tool in the strategy of preventive measures.

Criptococose canina: descrição no município deMossoró, Rio Grande do Norte, Brasil / Canine cryptococcosis: description in the municipality of Mossoro, Rio Grande doNorte, Brazil

A criptococose é uma micose sistêmica causada pelo fungo saprófita Cryptococcus neoformans. Oscães e os gatos são as espécies mais suscetíveis à doença. Todavia, a criptococose em pequenos animaisencontra-se pouco descrita nos estados do Nordeste do Brasil. Nesse sentido, relatou-se umcaso de criptococose em um canino oriundo da cidade de Mossoró, estado do Rio Grande do Norte.Uma cadela da raça poodle, com três anos de idade, foi encaminhada para consulta devido à rinitecrônica. O exame físico revelou secreção nasal serosa, estridores respiratórios e linfonodos poplíteoshipertrofiados. Foi colhido material (da cavidade nasal e linfonodos poplíteos) para exame citológicoe microbiológico. A citologia constatou estruturas leveduriformes, basofílicas, esféricas e com cápsulasmucóides, sugestivas de Cryptococcus. A cultura microbiológica isolou o fungo C. neoformans.A análise genotípica detectou que o agente pertencia à variedade grubii (sorotipo A). Prescreveu-separa a paciente um tratamento com itraconazol, na posologia de 10mg/kg, SID, por 90 dias. O animalapresentou adequada recuperação e não demonstrou sinais de recidiva da doença. Embora incomumno Nordeste brasileiro, a criptococose deve ser considerada em cães habitantes de tal região.(AU)

Cryptococcosis is a systemic mycosis caused by the saprophytic fungus Cryptococcus neoformans.Dogs and cats are the species most susceptible to the disease. However, in small animals cryptococcosisis rarely described in the Northeastern states of Brazil. Accordingly, we report a case of cryptococcosisin a dog coming from the city of Mossoro, state of Rio Grande do Norte. A three year old femalepoodle dog was referred for consultation due to chronic rhinitis. Physical examination revealed serousnasal discharge, stridor and hypertrophied popliteal lymph nodes. Material was collected (from thenasal cavity and popliteal lymphnodes) for cytological and microbiological examination. Cytologyshowed spherical, basophilic, yeast-like structures with mucoid capsules, suggestive of Cryptococcus.Microbiological culture isolated the fungus C. neoformans. The genotypic analysis detected that theagent belonged to the variety grubii (serotype A). It was prescribed for the patient a treatment withitraconazole at the dosage of 10 mg/kg, SID for 90 days. The animal showed adequate recovery and no signs of relapse. Although uncommon in the northeastern Brazil, cryptococcosis should be consideredin dogs living in that region.(AU)

Criptococose canina: descrição no município deMossoró, Rio Grande do Norte, Brasil / Canine cryptococcosis: description in the municipality of Mossoro, Rio Grande doNorte, Brazil

A criptococose é uma micose sistêmica causada pelo fungo saprófita Cryptococcus neoformans. Oscães e os gatos são as espécies mais suscetíveis à doença. Todavia, a criptococose em pequenos animaisencontra-se pouco descrita nos estados do Nordeste do Brasil. Nesse sentido, relatou-se umcaso de criptococose em um canino oriundo da cidade de Mossoró, estado do Rio Grande do Norte.Uma cadela da raça poodle, com três anos de idade, foi encaminhada para consulta devido à rinitecrônica. O exame físico revelou secreção nasal serosa, estridores respiratórios e linfonodos poplíteoshipertrofiados. Foi colhido material (da cavidade nasal e linfonodos poplíteos) para exame citológicoe microbiológico. A citologia constatou estruturas leveduriformes, basofílicas, esféricas e com cápsulasmucóides, sugestivas de Cryptococcus. A cultura microbiológica isolou o fungo C. neoformans.A análise genotípica detectou que o agente pertencia à variedade grubii (sorotipo A). Prescreveu-separa a paciente um tratamento com itraconazol, na posologia de 10mg/kg, SID, por 90 dias. O animalapresentou adequada recuperação e não demonstrou sinais de recidiva da doença. Embora incomumno Nordeste brasileiro, a criptococose deve ser considerada em cães habitantes de tal região.

Cryptococcosis is a systemic mycosis caused by the saprophytic fungus Cryptococcus neoformans.Dogs and cats are the species most susceptible to the disease. However, in small animals cryptococcosisis rarely described in the Northeastern states of Brazil. Accordingly, we report a case of cryptococcosisin a dog coming from the city of Mossoro, state of Rio Grande do Norte. A three year old femalepoodle dog was referred for consultation due to chronic rhinitis. Physical examination revealed serousnasal discharge, stridor and hypertrophied popliteal lymph nodes. Material was collected (from thenasal cavity and popliteal lymphnodes) for cytological and microbiological examination. Cytologyshowed spherical, basophilic, yeast-like structures with mucoid capsules, suggestive of Cryptococcus.Microbiological culture isolated the fungus C. neoformans. The genotypic analysis detected that theagent belonged to the variety grubii (serotype A). It was prescribed for the patient a treatment withitraconazole at the dosage of 10 mg/kg, SID for 90 days. The animal showed adequate recovery and no signs of relapse. Although uncommon in the northeastern Brazil, cryptococcosis should be consideredin dogs living in that region.