Leishmaniasis is a group of diseases caused by protozoa of Leishmania genus. The currently available treatments for this disease are expensive, present high toxicity and are associated to difficulties of healing and parasite resistance. Therefore, the development of strategies for leishmaniasis treatment is indispensable and includes reposition of existing drugs, as well as drug combination therapy. The aim of this study was to assess the nature of ketoconazole and antimony association on the cytotoxic effect against Leishmania (Leishmania) amazonensis amastigotes. The calculated mean sum of fractional 50% inhibitory concentration (ΣFIC50) was 2.54 and 1.43 for free and intracellular amastigotes, respectively, values that suggest an additive interaction between ketoconazole and antimony concerning to Leishmania toxicity only in the intramacrophage parasite form. Despite the clinical efficacy of ketoconazole-antimony combination has been shown in the literature, our study is the first to describe the nature of ketoconazole-antimony interaction against L. (L.) amazonensis amastigotes. Moreover, our results point out the need for future in vivo studies to confirm the nature of ketoconazole-antimony interaction and also to determine possible effective dosage regimens related to ketoconazole administration in association with the optimal lower dose of antimony.
Acidente por animais peçonhentos é um agravo de notificação compulsória. Devido ao grande número de casos no estado de Minas Gerais e ausência de informação sobre o agravo em Uberlândia, o estudo objetivou descrever o perfil epidemiológico dos acidentes por animais peçonhentos no município (2014-2018). Tratou-se de uma pesquisa observacional, descritiva, retrospectiva, baseada em dados secundários extraídos das fichas de Notificação Compulsória. Dos 1676 casos analisados, 1605 referiram-se a acidentes por animais peçonhentos. Os acidentes ocorreram principalmente em zona urbana, em mulheres para todos os animais peçonhentos, exceto serpentes e a faixa etária mais acometida foi 18-60 anos. Os escorpiões foram os principais agentes agressores, seguido por serpentes, aranhas e abelhas. As vítimas procuraram atendimento médico rapidamente, a maioria dos casos foi leve e não recebeu soroterapia. Praticamente todos os casos evoluíram para cura e poucos óbitos foram registrados. Acidentes causados por escorpiões/serpentes ocorreram mais nos meses chuvosos do ano e, para as aranhas/abelhas, foram constantes ao longo dos meses. As regiões anatômicas mais acometidas foram cabeça, seguido de membros superiores e tronco para abelhas e, membros inferiores e superiores para aranhas, escorpiões e serpentes. A principal manifestação local foi dor, manifestações sistêmicas foram menos comuns e complicações raras.
BACKGROUND
Leishmania
parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase.
OBJECTIVE
The present study aimed to better understand the biological response of
Leishmania (Leishmania) amazonensis
promastigotes at the cellular level after ketoconazole treatment.
METHODS
Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment.
FINDINGS
The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on
L. (L.) amazonensis
promastigotes (IFLA/BR/67/PH8 strain).
MAIN CONCLUSIONS
Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in
in vitro
models.
ABSTRACT:The purpose of this study was to describe clinic-epidemiological characteristics of leishmaniasis cases attended at the Clinical Hospital of Federal University of Uberlândia (CHU), state of Minas Gerais, from January 2000 to December 2013. This is a descriptive and retrospective review of medical records of patients diagnosed with leishmaniasis and treated at the CHU. 168 cases of leishmaniasis were analyzed and most patients were male, aged 23 to 60 years. For cutaneous and mucosal leishmaniasis, single lesions, located mainly in lower limbs and head (CL) and nasal mucosa (ML), were the most common clinical presentation. Regarding the diagnosis, the most performed methods for CL and ML were biopsy plus histopathology and biopsy plus immunohistochemistry; biopsy plus direct parasitological examination methods were the most frequent for VL. Most patients (84%) received treatment, mainly glucantime for both CL and ML; VL treatment was based on amphotericin B or glucantime. According to data from Sistema de Informações de Agravos de Notificação (SINAN), the Brazilian information system to notify and investigate cases of diseases and their aggravations, no case has been confirmed as autochthonous. It is noteworthy the underreporting of cases and the lack of complete information in medical records. Our results may contribute to a better understanding of the real situation in Uberlândia region concerning to leishmaniasis.
Neste trabalho, investigou-se a avaliação diagnóstica como instrumento de pesquisa-ação para planejar intervenções no âmbito escolar. Foram amostrados 60 alunos de 3º e 4º séries de uma Escola Estadual de Uberlândia - MG. A pesquisa foi dividida em três etapas: avaliação diagnóstico inicial - entrevistas semi-estruturadas, produção de material pelos alunos e questionário; intervenção - duas oficinas e o "Vigilante-mirim"; avaliação final - feira de ciências. Evidências mostraram que a avaliação diagnóstica foi positiva para o planejamento. Assim, a educação em saúde pressupõe explorar, simultaneamente, conceitos científicos aos valores, crenças e inter-relações sociais para a aproximação entre conteúdo curricular e cotidiano do aluno, levando ao aprendizado significativo.
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