Browsing by Author "Salles, Beatriz Cristina Silveira"

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    Alterações inflamatórias induzidas pelo tratamento com Cloridrato de Amiodarona em modelo experimental da infecção pelo Trypanosoma cruzi.
    (2014) Salles, Beatriz Cristina Silveira; Silva, André Talvani Pedrosa da; Silva, André Talvani Pedrosa da; Machado, Evandro Marques de Menezes; Silva, Vanessa Pinho da
    A doença de Chagas se desenvolve após a infecção pelo protozoário Trypanosoma cruzi. Este parasito desencadeia uma resposta imune em seu hospedeiro mamífero mediado por células, anticorpos e mediadores inflamatórios, culminando em destruição do tecido e perda funcional do órgão, a exemplificar, o coração e o trato gastrointestinal em humanos. Fármacos com o intuito de amenizar os danos funcionais cardíacos têm sido empregados na clínica médica e, nos últimos anos, também identificadas suas ações sob a resposta imune. Dentre estes fármacos, encontra-se o antiarrítmico Cloridrato de Amiodarona (CA). O objetivo deste estudo é avaliar a ação do tratamento com o CA na infecção aguda pela cepa VL-10 do T. cruzi em modelo murino. Para tal, realizou-se a infecção de camundongos C57BL/6, agrupados em (i) animais tratados com 30mg/kg de CA diariamente e (ii) animais tratados com PBS 1x + metilcelulose 0,5% (veículo). Após 30 dias de tratamento, realizou-se a necrópsia e coleta de soro e órgãos (coração, fígado e baço) para a dosagem de citocinas e avaliação do peso relativo dos órgãos, respectivamente, além de análise histológica. Observou-se redução nos níveis dos parasitas sanguíneos ao final do tratamento e redução dos níveis plasmáticos e cardíacos de TNF-α e CCL2, mas não de CCL5 e IL-10. Além disso, observou-se menor aumento do peso relativo do coração e baço associado ao tratamento com CA. Estes dados sugerem uma ação parcial do CA sobre T. cruzi e a resposta imune do hospedeiro, principalmente mediada por TNF- e CCL-2, na infecção experimental pelo T. cruzi, cepa VL-10, em animais isogênicos C57BL/6.
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    Expression and production of cardiac angiogenic mediators depend on the Trypanosoma cruzi-genetic population in experimental C57BL/6 mice infection.
    (2017) Bajracharya, Deena Shrestha; Bajracharya, Bijay; Costa, Guilherme de Paula; Salles, Beatriz Cristina Silveira; Leite, Ana Luísa Junqueira; Menezes, Ana Paula de Jesus; Souza, Débora Maria Soares de; Oliveira, Laser Antônio Machado de; Silva, André Talvani Pedrosa da
    Mammalian cardiac cells are important targets to the protozoan Trypanosoma cruzi. The inflammatory reaction in the host aims at eliminating this parasite, can lead to cell destruction, fibrosis and hypoxia. Local hypoxia iswelldefined stimulus to the production of angiogenesis mediators. Assuming that different genetic T. cruzi populations induce distinct inflammation and disease patterns, the current study aims to investigate whether the production of inflammatory and angiogenic mediators is a parasite strain-dependent condition. C57BL/6 mice were infectedwith the Y and Colombian strains of T. cruzi and euthanized at the 12th and 32nd days, respectively. The blood and heart tissue were processed in immune assays and/or qPCR (TNF, IL-17, IL-10, CCL2, CCL3, CCL5, CCR2, CCR5 and angiogenic factors VEGF, Ang-1, Ang-2) and in histological assays. The T. cruzi increased the inflammatory and angiogenicmediators in the infectedmicewhen theywere compared to non-infected animals.However, the Colombian strain has led to higher (i) leukocyte infiltration, (ii) cardiac TNF and CCL5 production/expression, (iii) cardiac tissue parasitism, and to higher (iv) ratio between heart/body weights. On the other hand, the Colombian strain has caused lower production and expression VEGF, Ang-1 and Ang-2, when it was compared to the Y strain of the parasite. The present study highlights that the T. cruzi-genetic population defines the pattern of angiogenic/inflammatory mediators in the heart tissue, and that itmay contribute to themagnitude of the cardiac pathogenesis. Besides, such assumption opens windows to the understanding of the angiogenic mediator's role in association with the experimental T. cruzi infection.
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    High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection.
    (2019) Carvalho, Gerusa Brandão de; Costa, Lourena Emanuele; Lage, Daniela Pagliara; Ramos, Fernanda Fonseca; Santos, Thaís Teodoro de Oliveira; Ribeiro, Patrícia Aparecida Fernandes; Dias, Daniel Silva; Salles, Beatriz Cristina Silveira; Lima, Mariana Pedrosa; Carvalho, Lívia Mendes; Dias, Ana C. S.; Alves, Patrícia Terra; Franklin, Michelle Lucrécio; Silva, Renata A. M.; Duarte, Mariana Costa; Souza, Daniel Menezes; Roatt, Bruno Mendes; Chávez Fumagalli, Miguel Angel; Goulart Filho, Luiz Ricardo; Teixeira Junior, Antonio Lucio; Coelho, Eduardo Antônio Ferraz
    In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection
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    Trypanosoma cruzi antigens induce inflammatory angiogenesis in a mouse subcutaneous sponge model.
    (2015) Silva, Francisca Hildemagna Guedes da; Bajracharya, Deena Shrestha; Salles, Beatriz Cristina Silveira; Figueiredo, Vivian Paulino; Lopes, Laís Roquete; Dias, Luiza; Barcelos, Luciola da Silva; Moura, Sandra Aparecida Lima de; Andrade, Silvia Passos de; Silva, André Talvani Pedrosa da
    Acute inflammation and angiogenesis are persistent features of several pathological conditions induced by biological agents leading to the resolution of local and systemic events. Glycoproteins derived from the protozoan Trypanosoma cruzi are suggested to mediate angiogenesis induced by inflammatory cells with still undescribed mechanisms. In this study, we investigated the effects of total antigen from trypomastigote forms of T. cruzi (Y strain), inoculated in sponges 24 h after implantation inmice, on angiogenesis, inflammatory cell pattern and endogenous production of inflammatory and angiogenicmediators on days 1, 4, 7 and 14 post-implant. There was an increase in hemoglobin content and in the number of blood vessels associated with T. cruzi antigen stimuli on the 14th day, assessed by the hemoglobin of the implants and by morphometric analysis. However, these antigens were not able to increase type I collagen content on the 14th day. Parasite antigens also induced high production of vascular endothelial growth factor (VEGF) and inflammatory mediators TNF-alpha, CCL2 and CCL5 on the 7th day in sponges when compared to the unstimulated group. Neutrophils and macrophages were determined by measuring myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) enzyme activities, respectively. Only NAG was increased after stimulation with antigens, starting from day 4 and peaking at day 7. Together, these data showed that antigens fromthe Y strain of T. cruzi are able to promote inflammatory neovascularization probably induced by macrophage-induced angiogenic mediators in T. cruzi antigen-stimulated sponges in Swiss mice.