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Conselho Nacional de Desenvolvimento Científico e Tecnológico Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Fundação de Amparo a Pesquisa do Estado de Minas Gerais Trypanosma cruzi, é o agente causador da doença de Chagas. Essa tripanosomíase tem se tornado um problema de saúde mundial devido a migrações de latinoamericanos à países não endêmico. Na América Latina com o sucesso da implementação do controle da infestação doméstica pelo vetor e de transfusões sanguíneas, a importância da transmissão congênita tem aumentado recentemente. Considerando a cuidadosa regulação do sistema imune durante a gestação, nosso objetivo foi investigar as mudanças causadas pela infecção por T.cruzi ao sistema imune na progressão da gestação. Foram utilizadas cepas G e Y de T cruzi para infectar fêmeas BALB/c antes ou depois do acasalamento com machos não infectados. A presença da rolha vaginal foi usada como indicativo de acasalamento. As fêmeas foram eutanasiadas 8 dias depois da confirmação da rolha vaginal. Foram usados três grupos controles, fêmeas apenas infectadas, apenas grávidas e nenhuma das situações. Dois grupos de fêmeas foram infectadas antes do acasalamento e dois grupos 4 dias após a confirmação da rolha vaginal. O útero e o baço foram coletados para análises de imunohistoquímica, qPCR, imunfluorescência e dosagem de citocinas. Nossos resultados mostraram que, apesar do padrão de marcação para MMPs ter sido semelhante entre os grupos, a cepa mais virulenta de T.cruzi pode impedir a progressão da gestação quando anterior ao acasalamento; a infecção aumentou de forma sistêmica citocinas como IFN-γ, IL-1β e IL-4; e os leucócitos no ambiente uterino se apresesntaram alterados, respondendo de forma local à alteração sistêmica causada pela infecção. Em conclusão, esse trabalho sugere que a infecção por T.cruzi pode prejudicar o desenvolvimento da gestação e a resposta local a uma infecção sistêmica foi capaz de controlar a infecção e permitir a progressão da gestação sob algumas dentre as condições analisadas. Trypanosma cruzi is the causative agent of Chagas disease. This trypanosomiasis has become a global public health problem due to migration of Latin Americans to non-endemic countries. In Latin America with the succesful implementation of control domiciliated vector infestation and blood transfusion, the importance of congenital transmission has recently increased. Considering the tight regulation of immune system during gestation, we aimed to investigate the changes in the immune system caused by T.cruzi infection in the gestation outcome. T cruzi G and Y strain were used to infect female BALB/c mice before or after mating with non-infected male mice. The presence of vaginal plug was used as indicative of mating. Females were euthanized 8 days after confirmation of vaginal plug. We used three female control groups, only infected, only infected and non-infected and non-pregnant females. Two groups were infected before mating and other two were infected 4 days after confirmation of vaginal plug. The uterus and spleen were collected to immunochemistry, qPCR, immunofluorescence and cytokine analysis. Our results showed that despite the MMP’s identification being similarly among groups, T.cruzi higher virulent strain can impaire gestation outcome prior mating; the infection also increased cytokines like IFN-γ, IL-1β and IL-4; and leucocytes in uterine environment was altered, responding locally to systemic changes caused by T.cruzi infection. In conclusion this work suggests that T.cruzi infection can impaire gestation outcome and local response to sistemic infection was able to control the infection allowing pregnancy development in some conditions. Dissertação (Mestrado)

The biological applicability of nanomaterials has been limited due to cytotoxicity. Studies have described the effects of nanomaterials on different tissues and cell types, but their actions on immune cells are less elucidated. This study describes unprecedented in vitro and in vivo antioxidant activities of cadmium selenide magic-sized quantum dots (CdSe MSQDs) with implications on rheumatoid arthritis. While the generation of ROS induced by nanomaterials is linked to cytotoxicity, we found that CdSe MSQDs reduced ROS production by neutrophils and macrophages following opsonized-zymosan stimuli, and we did not find cytotoxic effects. Interestingly, inherent antioxidant properties of CdSe MSQDs were confirmed through DPPH, FRAP, and ORAC assays. Furthermore, CdSe MSQDs reduced ROS levels generated by infiltrating leukocytes into joints in experimental model of rheumatoid arthritis. Briefly, we describe a novel application of CdSe MSQDs in modulating the inflammatory response in experimental rheumatoid arthritis through an unexpected antioxidant activity.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Infarto Agudo do Miocárdio (IAM) é uma doença cardiovascular e está entre as principais causas de mortes no mundo. Pacientes que são atendidos em pronto-atendimentos com suspeita de IAM passam por exames de atividade elétrica cardíaca e busca por biomarcadores de lesão cardíaca, geralmente troponinas e creatina-quinase. A detecção desses biomarcadores pode ser feita utilizando biossensores, dispositivos analíticos capazes de converter uma resposta biológica em um sinal de outra natureza. O objetivo desse trabalho foi construir um biossensor eletroquímico utilizando matrizes poliméricas enriquecidas com nanomateriais, tendo como alvo marcadores biológicos para IAM. Para isso as matrizes foram colocadas em contato com a superfície dos eletrodos e a funcionalização, por meio da deposição do polímero, foi induzida através da passagem de corrente. Posteriormente a modificação foi validada a partir de leituras de voltametria cíclica. Através de microscopia eletrônica de varredura foi constatado que não houve alteração na superfície microscópica dos eletrodos tratados. Entretanto, a modificação foi capaz de melhorar o sinal de leitura, aumentando a área ativa, a densidade de corrente e homogeneizando as leituras entre os eletrodos. Duas estratégias de reconhecimento de analito foram propostas, com variação na montagem da biocamada. As duas estratégias foram capazes de diferenciar amostras positivas de negativas. A utilização dessa metodologia traz vantagens pelo fato de as matrizes poliméricas serem de fácil obtenção e o processo de modificação simplificado, além de poderem ser enriquecidas com diversos materiais. Garantir que a etapa de funcionalização do eletrodo seja eficiente é essencial para a construção de um biossensor, pois garante também que a deposição das moléculas de captura se dê de maneira semelhante a cada repetição. A possibilidade de se ter um biossensor que utilize poucos reagentes é uma vantagem quando se fala em praticidade e baixo custo. Por fim, nanomateriais associados a estruturas poliméricas foi uma maneira eficiente de estabilizar e modificar a superfície de eletrodos screen-printed e a plataforma aqui desenvolvida pode ser aprimorada para se tornar uma ferramenta clínica para diagnóstico de IAM. Acute Myocardial Infarction (AMI) is a cardiovascular disease and is among the main causes of death worldwide. Patients who are seen in emergency rooms with suspected AMI undergo examinations of cardiac electrical activity and search for biomarkers of cardiac injury, usually troponins and creatine kinase. The detection of these biomarkers can be done using biosensors, analytical devices capable of converting a biological response into a signal of another nature. The objective of this work was to build an electrochemical biosensor using polymeric matrices enriched with nanomaterials, targeting biological markers for AMI. For this, the matrices were placed in contact with the surface of the electrodes and functionalization, through the deposition of the polymer, was induced through the passage of current. Subsequently, the modification was validated based on cyclic voltammetry readings. Through scanning electron microscopy, it was found that there was no change in the microscopic surface of the treated electrodes. However, the modification was able to improve the reading signal, increasing the active area, the current density and homogenizing the readings between the electrodes. Two analyte recognition strategies have been proposed, with variation in the biological layer assembly. The two strategies were able to differentiate positive from negative samples. The use of this methodology has advantages because the polymeric matrices are easy to obtain and the modification process simplified, in addition to being enriched with different materials. Ensuring that the efficient electrode functionalization step is essential for the construction of a biosensor, as it also guarantees that the deposition of the capture molecules takes place in a similar way with each repetition. The possibility of having a biosensor that uses few reagents is an advantage when it comes to practicality and low cost. Finally, nanomaterials associated with polymeric structures was an efficient way to stabilize and modify the surface of screen-printed electrodes and the platform developed here can be improved to become a clinical tool for the diagnosis of AMI. Tese (Doutorado) 2022-11-18

Trypanosoma cruzi has high biological and biochemical diversity and variable tissue tropism. Here we aimed to verify the kinetics of cytokine and chemokine in situ secretion in animals infected with two distinct T. cruzi strains after oral inoculation. Also, we investigated parasite migration, residence and pathological damage in stomach, heart and spleen. Our results showed that host immune response against T. cruzi infection is an intricate phenomenon that depends on the parasite strain, on the infected organ and on the time point of the infection. We believe that a wide comprehension of host immune response will potentially provide basis for the development of immunotherapeutic strategies in order to clear parasitism and minimize tissue injury. In this context, we find that KC poses as a possible tool to be used.

Background Leishmaniasis causes alterations and lesions in the genital system, which leads to azoospermia and testicular atrophy in animals during the chronic phase of the infection. The aim of this study was to reveal the kinetics of Leishmania chagasi infection in the genital system of male golden hamsters (Mesocricetus auratus). Methods Animals were intraperitoneally inoculated with amastigotes from L. chagasi. At different time points animals were euthanized and genital organs processed for histo-pathological, qPCR, cytokines and testosterone detection assays. Results Our results showed a high parasite load in testis, followed by an increase of pro-inflammatory cytokines IL1-β, TNF-α and IFN-γ, and testosterone. Subsequently, IL-4 expression was upregulated and basal parasite persistence in testis was observed using the experimental approach. Conclusion Extracellular amastigotes migrated to the epididymis posing as a potential major factor of parasite persistence and venereal transmission of L. chagasi infection in hamsters. Electronic supplementary material The online version of this article (doi:10.1186/s40249-016-0122-0) contains supplementary material, which is available to authorized users.