BackgroundGlycosylphosphatidylinositol is a surface molecule important for host-parasite interactions. Mannosyltransferase (GPI-14) is an essential enzyme for adding mannose on the glycosylphosphatidyl group. This study attempted to overexpress the GPI-14 gene in Leishmania braziliensis to investigate its role in the antimony-resistance phenotype of this parasite.ResultsGPI-14 mRNA levels determined by quantitative real-time PCR (qRT-PCR) showed an increased expression in clones transfected with GPI-14 compared to its respective wild-type line. In order to investigate the expression profile of the surface carbohydrates of these clones, the intensity of the fluorescence emitted by the parasites after concanavalin-A (a lectin that binds to the terminal regions of α-D-mannosyl and α-D-glucosyl residues) treatment was analyzed. The results showed that the clones transfected with GPI-14 express 2.8-fold more mannose and glucose residues than those of the wild-type parental line, indicating effective GPI-14 overexpression. Antimony susceptibility tests using promastigotes showed that clones overexpressing the GPI-14 enzyme are 2.4- and 10.5-fold more resistant to potassium antimonyl tartrate (SbIII) than the parental non-transfected line. Infection analysis using THP-1 macrophages showed that amastigotes from both GPI-14 overexpressing clones were 3-fold more resistant to SbIII than the wild-type line.ConclusionsOur results suggest the involvement of the GPI-14 enzyme in the SbIII-resistance phenotype of L. braziliensis.
BACKGROUND The mechanism of resistance to Sb III in Leishmania is complex, multifactorial and involves not only biochemical mechanisms, but also other elements, such as the immune system of the host. OBJECTIVES In this study, putative changes in the immunological profile of human monocytes infected with wild-type (WT) and antimony (Sb III)-resistant Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum lines were evaluated. METHODS Susceptibility assays WT and SbIII-resistant L. braziliensis and L. infantum were performed using lines THP-1 human monocytic lineage. Phagocytic capacity, cytokine profile, intracellular nitric oxide (NO) production and surface carbohydrate residues profile were performed in peripheral blood monocytes by flow cytometry. FINDINGS The phagocytic capacity and intracellular NO production by classical (CD14 ++ CD16-) and proinflammatory (CD14 ++ CD16 +) monocytes were higher in the presence of L. infantum lines compared to L. braziliensis lines. The results also highlight proinflammatory monocytes as the cellular subpopulation of major relevance in a phagocytosis event and NO expression. It is important to note that L. infantum induced a proinflammatory cytokine profile characterised by higher levels of TNF-α in culture supernatant than L. braziliensis. Conversely, both Leishmania lines induce high levels of IL-6 in culture supernatant. Analysis of the expression profile of surface carbohydrates showed that L. braziliensis presents 4.3-fold higher expression of galactose(β1,4)N-acetylglucosamine than L. infantum line. Interestingly, the expression level of α-N-acetylgalactosamine residues was 2-fold lower in the Sb III-resistant L. braziliensis line than its counterpart WT line, indicating differences in surface glycoconjugates between these lines. MAIN CONCLUSIONS Our results showed that L. braziliensis and L. infantum induce different innate immune responses and a highly inflammatory profile, which is characteristic of infection by L. infantum, the species associated with visceral disease.
Thus, it was possible to verify that a high apoptotic index was associated with a lower chance of tumor differentiation in carcinomas, while a greater number of total nucleolus organizer regions, cells expressing nucleolus organizer regions above average and a higher growth fraction were associated with greater likelihood of abnormal cell proliferation and increased tumor differentiation.
O diabetes é uma doença caracterizada por distúrbios metabólicos que resultam na elevação da glicose no sangue, de forma que pacientes diabéticos necessitam de cuidados a fim de controlar os níveis de glicemia. Uma das consequências dessa patologia é o surgimento do pé diabético, que se traduz em problemas circulatórios, neurológicos e ortopédicos. Outras intercorrências podem aparecer, como as úlceras arteriais e venosas, as quais, se não tratadas, têm significativa chance de evoluírem e levarem à amputação do membro inferior afetado. Os podólogos auxiliam a medicina na prevenção de problemas relacionados aos pés e são, portanto, os profissionais de saúde capacitados aos cuidados dessas ulcerações. Além de atuarem de modo preventivo na orientação de pacientes, eles também desenvolvem um trabalho de acompanhamento e higienização. A profilaxia realizada por um podólogo é a melhor medida para o não surgimento de lesões nos pés e, na iminência dessas, caberá orientar o paciente de modo a não extensão do trauma.
As úlceras venosas são lesões de pele comuns nos membros inferiores, causadas por problemas circulatórios. Devido a sua complexidade, necessitam do acompanhamento de uma equipe multidisciplinar. Neste contexto, o podólogo presta grande contribuição no atendimento primário desses pacientes pois, através de uma avaliação criteriosa dos membros inferiores, pode tratá-los e encaminhá-los ao especialista adequado. Neste estudo, foi realizada uma pesquisa de artigos científicos na base de dados do Google Acadêmico e SciELO, com o objetivo de determinar o processo de formação e desenvolvimento das úlceras venosas nos membros inferiores. Foram explanados os mecanismos através dos quais o indivíduo pode adquirir essas lesões, e foram discutidos os impactos ocasionados na rotina do paciente. A partir da análise dos artigos, foi verificado um resultado positivo quando há o trabalho da equipe multidisciplinar no atendimento ao paciente, buscando soluções e a melhora de sua qualidade de vida; e o podólogo auxilia na prevenção desta condição patológica conforme citado acima.
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