Modulação da resposta imune do hospedeiro por componentes da parede celular de Cryptococcus neoformans

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Patologia Molecular, 2017.A incidência de infecções fúngicas sistêmicas vem se elevando com o aumento de situações em que se observa supressão do sistema imune do paciente, tornando-se este, um problema de saúde mundial. Cryptococcus neoformans é um fungo cosmopolita e mundialmente distribuído, que se apresenta como uma levedura encapsulada, presente no ambiente, acometendo, especialmente, pacientes imunodeprimidos e apresentando índice de mortalidade acima de 60%. Embora existam extensivos estudos sobre a estrutura capsular das leveduras do fungo C. neoformans, pouco se sabe sobre a interação deste patógeno com o hospedeiro, particularmente no que diz respeito aos componentes de sua parede celular. Estudos em algumas espécies de fungos vem apontando os componentes presentes na parede destes micro-organismos, como forte imunomodulador durante a interação patógeno-hospedeiro, podendo estes componentes serem empregados em estudos na elaboração de vacinas. Nesse trabalho, foi avaliada a capacidade da fração 1 (F1) extraída da parede celular de diferentes linhagens de C. neoformans em modular a resposta imune do hospedeiro. Inicialmente, foram realizados ensaios in vitro, para avaliar a viabilidade celular de macrófagos de camundongo, empregando diferentes concentrações das frações, extraídas a partir das linhagens de C. neoformans H99, B3501 e da linhagem mutante cap67Δ. Em seguida, foi avaliada a capacidade das fracões em induzir a produção de citocinas nas células do hospedeiro. Os dados mostram que, após 18 horas de interação, as frações das linhagens B3501 e cap67Δ induziram elevados níveis de TNF-α, demonstrando que há uma prévia ativação desses fagócitos sem alterar a viabilidade celular. Além disso, foi avaliado a atividade microbicida e de fagocitose de macrófagos previamente estimulados com essas frações, seguindo com interação com leveduras de C. neoformans. Os dados demonstram que, no intervalo de 24 horas após interação, houve uma diminuição significativa no número de leveduras recuperadas a partir dos macrófagos. Além disso, houve também um aumento significativo no número de leveduras fagocitadas. Nos testes in vivo, usando camundongos fêmeas da linhagem C57Bl/6, as frações foram previamente aplicadas nos animais, e em seguida os animais foram infectados com leveduras de C. neoformans H99. Os resultados mostram um aumento significativo na sobrevida dos animais que receberam o tratamento com as frações 14 em relação aos não tratados. Em conjunto, esses resultados claramente sugerem que os estímulos realizados com a fração F1 da parede de C. neoformans, são capazes de imunomodulador a resposta do hospedeiro, resultando em uma ação protetora contra a infecção a fúngica. Esses resultados abrem margem para possíveis alvos terapêuticos, além de contribuir com os estudos na elaboração de vacinas contra a infecção causada por C. neoformans.The incidence of systemic fungal infections has been aggravated by the increase in diseases that induce a suppression of the immune system, making it a global health problem. Cryptococcus neoformans is a globally distributed, cosmopolitan fungus that presents as an encapsulated yeast present in the environment, especially affecting immunosuppressed patients and showed a mortality rate above 60%. Although there are extensive studies on the capsular structure, composed especially of polysaccharides involving the yeasts of C. neformans, little is known about the interaction of this pathogen with the host, particularly with respect to the components of its cell wall. Studies in some species of fungi have pointed out the components present in the wall of these microorganisms, as a strong immunomodulator during pathogen-host interaction, and these components can be used in studies in the elaboration of vaccines. In this study the captivity of the different fractions extracted from the cell wall of C. neoformans was evaluated in modulating the immune response of the host. Initially, in vitro assays were performed to assess the cell viability of mouse macrophages cultured with different concentrations of b-glucan fraction from H99, B3501 and a mutant strain cap67Δ strains of C. neoformans. Following, it was investigated the ability of these fractions to induce cytokine production in host cells. The data show that after 18 hours interaction, the fractions of strains B3501 and cap67Δ increased the TNF-α levels, showing that these fractions are able to activate the macrophage response without affecting the cell viability. Moreover, we evaluate the microbicidal and phagocytosis capacity of macrophages, previously stimulated with these fractions, during interaction with C.neoformans yeast. The data showed that after 24 hour of interaction, the number of yeasts recovered from macrophages was significantly decreased. Furthermore, there was a significant increase in the number of yeast phagocytosed. Mice treated with b-glucan fraction previously of C. neoformans infection showed a increased survival compared to the mouse not treatment. Taken together, these results clearly suggest that cell wall components is able to stimulate host immune response, resulting in an increased host immunity. These results open to the new therapeutic possibilities, beyond gives support on adjuvant therapeutic research during C. neoformans infections

BRIEF REVIEW ON THE MEDICINAL USES AND ANTIMICROBIAL ACTIVITY OF DIFFERENT PARTS OF SCHINUS TEREBINTHIFOLIUS RADDI

Populations all over the world make use of medicinal plants to treat health problems. Plants are pertaining to the Anacardiaceae family which largely occur throughout Brazil, such as the Schinus terenbithifolius Raddi species, commonly known as aroeira, have been adopted in Brazilian folk medicine for the treatment of countless diseases and have also been indicated and studied as an antimicrobial agent. Several parts of the plant such as the leaves, the fruits and barks have their antimicrobial activity attested. The indication for the part of the plant to be used as an antimicrobial for folk medicine is yet to be made clear. Several parts are used and in some cases, for similar ends. There are no conclusive studies that describe the difference in antimicrobial action from each plant part. In this review, we investigated the antimicrobial activity of the Schinus terenbithifolius Raddi and then the information available in the literature was organized. The antimicrobial activity described in scientific publications according to the plant parts applied and the type of extract acquired in order to determine such activity

Antiproliferative activity of extracts of Euphorbia tirucalli L (Euphorbiaceae) from three regions of Brazil

Purpose: To investigate Euphorbia tirucalli extract for probable geographic variations in its antiproliferative activity.Methods: The aerial parts of E. tirucalli were collected in the Brazilian states of Mato Grosso, Rio de Janeiro, Pará, Minas Gerais and Santa Catarina. The 70 % ethanol extract was obtained according to the procedure described in Brazilian Homeopathic Pharmacopeia. The antiproliferative activity of extracts, in concentrations of 62, 125, 250, and 500 μg mL-1, was tested against leukemia (HL-60), lymphoma (Daudi) and melanoma (B16F10) cell lines using methyl thiazol tetrazolium assay (MTT). Phytochemical analysis were carried out using High-performance liquid chromatography-diode array (HPLC-UV-DAD) and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI(-) FT-ICR MS) assays.Results: There was significant regional variability in the cytotoxicity of E. tirucalli extracts in a dosedependent manner. The extracts had similar activity towards leukemia cell line HL-60, decreasing cell viability to about 60 – 70 %. The extract showed the presence of ellagitannins, flavonoids, veracylglucan, and acid triterpenes as the major compounds.Conclusion: While the results support the ethnopharmacological use of E. tirucalli throughout Brazil, regional quantitative differences found in some classes of secondary metabolites may explain the variations observed in antitumor activity.Keywords: Aveloz, Cancer, Cytotoxicity, Antiproliferative, Ethnopharmacological, Traditional medicin

Filling Materials in Brittle Structures as Indicator of Cenozoic Tectonic Events in Southeastern Brazil

The filling materials in brittle structures can provide useful information about the Cenozoic evolution developed over proterozoic terrains. When these materials are affected by faults, they record deformation phases that can be determined chronologically and, in the occurrence of lateritic materials, it is possible to infer the paleoenvironmental conditions during the mineral formation. This work aimed to identify crystalline phases of brittle structure filling materials and to propose evolutionary interpretations for Cenozoic tectonic reactivation based on literature data. The study area is located in the Southern part of the Espírito Santo State, near the Brazilian Southeastern Continental Margin, where proterozoic geological structures have been reactivated since the mesozoic rift phase, up to the Holocene. The mineral assemblage found in the filling materials includes primary minerals such as quartz, muscovite, microcline, rutile, titanite, and bannisterite; and the weathering minerals such as kaolinite, illite, hematite, goethite, hydrobiotite, lithiophorite and, birnessite. The mineralogical association found in the filling materials denotes the action of fluid phases with mineral precipitation at the brittle discontinuities during the weathering processes that occurred during the Cenozoic, probably between the Miocene and the Pleistocene. The faults, which striations are marked on the filling materials, originated after (in the case of the manganese oxides) or during (in the case of the illite) the mineral formation, indicating that the maximum age of these faults is in the Miocene. The origin of the brittle structures that affected the filling materials studied here is linked to the uplifting of the Continental Brazilian Margin, when ancient geological structures were reactivated as normal faults due to the local action of an extensional regime.The filling materials in brittle structures can provide useful information about the Cenozoic evolution developed over proterozoic terrains. When these materials are affected by faults, they record deformation phases that can be determined chronologically and, in the occurrence of lateritic materials, it is possible to infer the paleoenvironmental conditions during the mineral formation. This work aimed to identify crystalline phases of brittle structure filling materials and to propose evolutionary interpretations for Cenozoic tectonic reactivation based on literature data. The study area is located in the Southern part of the Espírito Santo State, near the Brazilian Southeastern Continental Margin, where proterozoic geological structures have been reactivated since the mesozoic rift phase, up to the Holocene. The mineral assemblage found in the filling materials includes primary minerals such as quartz, muscovite, microcline, rutile, titanite, and bannisterite; and the weathering minerals such as kaolinite, illite, hematite, goethite, hydrobiotite, lithiophorite and, birnessite. The mineralogical association found in the filling materials denotes the action of fluid phases with mineral precipitation at the brittle discontinuities during the weathering processes that occurred during the Cenozoic, probably between the Miocene and the Pleistocene. The faults, which striations are marked on the filling materials, originated after (in the case of the manganese oxides) or during (in the case of the illite) the mineral formation, indicating that the maximum age of these faults is in the Miocene. The origin of the brittle structures that affected the filling materials studied here is linked to the uplifting of the Continental Brazilian Margin, when ancient geological structures were reactivated asnormal faults due to the local action of an extensional regime

Avaliação de cultivares de milho visando à produção de minimilho na região norte do Estado de Minas Gerais.

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O uso pré hospitalar do ácido tranexâmico em vítimas de trauma: uma revisão da literatura / The pre-hospital use of tranexamic acid in trauma victims: a literature review

O trauma é o principal causador de morbimortalidade na população adulta, principalmente nos homens, constituindo uma importante causas de morte evitável. Diante disso, torna-se essencial um atendimento sistematizado com estratégias que visam diminuir as suas complicações. O ácido tranexâmico é uma droga muito utilizada na prática clínica, porém seu uso pré-hospitalar segue discutível para contenção de hemorragias. Este estudo é uma revisão integrativa de literatura que busca conscientizar, reconhecer e sintetizar a produção de conhecimento acerca desse tema. Foi feito um levantamento das publicações na área da saúde consultando os artigos das bases de dados Google Scholar, Scielo e Biblioteca Virtual de Saúde e consultando o livro ATLS 10a edição. Desta forma, foram obtidos 8 artigos que compuseram o corpus analítico deste trabalho. Logo, identifica-se a contribuição do ácido tranexâmico em situações em que é necessário conter rapidamente hemorragias. Concluiu-se então que seu uso pré-hospitalar é de suma valia para a condução dos traumas e que as publicações e estudos comparativos são de extrema importância para atualizar os protocolos de emergências no Brasil e no mundo

Facies analysis and depositional environments of the Vazante Group in the region of Morro Agudo mine, Paracatu, northwest of Minas Gerais state, Brazil

Rochas do Grupo Vazante afloram no noroeste do estado de Minas Gerais, em uma faixa contínua de aproximadamente 250 km, da região de Vazante, ao sul, até Unaí, ao norte. Nessa região está localizada a mina de zinco e chumbo de Morro Agudo, que juntamente com os depósitos de Vazante, Ambrósia e Fagundes, todos hospedados no Grupo Vazante, compõe a principal província zincífera do país. Foram descritas, em seis testemunhos de sondagem e afloramentos de campo na região, 12 fácies sedimentares e quatro associações de fácies (AFs), que indicam deposição em ambiente de margem passiva mista carbonática-siliciclástica. A associação mais basal (AF01) é composta por pelitos e ritmitos silto-arenosos carbonosos, representando sedimentação em plataforma profunda de baixa declividade, em regime de transgressão marinha. Após a inundação máxima, em trato de mar alto, depositou-se a AF02 em ambiente de recife com barreiras em borda de plataforma, composta por dolomitos laminados com estromatólitos, dolarenitos e brechas dolareníticas, e ainda pelitos carbonáticos carbonosos com fácies diamictito. O abaixamento do nível relativo do mar gerou uma regressão forçada e a deposição da AF03 em trato de sistema do estágio de queda. É composta, na base, por diamictito argilo-carbonoso com fragmentos de AF02, passando a pelito e ritmito silto-arenoso. A retomada da subida do nível relativo do mar proporcionou a deposição da AF04 e ainda de rochas da AF03 em posição mais distal. A AF04 é composta por dololutitos argilosos laminados e maciços, e dolarenitos intraclásticos depositados em plataforma carbonática. O padrão de empilhamento observado sugere que a deposição de todas as unidades ocorreu progressivamente, em processo de subida do nível relativo do mar Vazante Group rocks outcrop in the northwest of Minas Gerais state, in a continuous belt of approximately 250 km, from the region of Vazante city, in the south, to Unaí city, in the north. In this region is the zinc and lead mine of Morro Agudo, which together with the deposits of Vazante, Ambrósia and Fagundes, all housed in the Vazante Group, make up the main zinc province of the country. Twelve sedimentary facies and four facies associations (AFs) were described in six drill holes and outcrops, that indicate deposition in a carbonate-siliciclastic mixed passive margin setting. The most basal association is AF01, composed by carbonaceous mudstone and silt-sand rhythmic, representing sedimentation in a deep platform of low slope angle, in a regime of marine transgression. After the maximum flood surface, in the highstand systems tract, AF02 was deposited in a reef setting with a barrier at the platform edge. It is composed of laminated dolomites with stromatolites, dolarenites and dolarenite breccia, and carbonate carbonaceous mudstones with interleaved diamictite facies. The fall in relative sea level led to a forced regression and the deposition of AF03 in a forced regressive system’s tract. It is composed, at the base, by carbonaceous diamictite with AF02 fragments, passing to mudstone and silt-sand rhythmithes. The return of the rise of the relative sea level provided the deposition of AF04 and AF03 rocks in a more distal position. AF04 is composed by laminated and massive argillaceous dololutite, and intraclastic dolarenite, deposited in carbonate marine platform. The observed stacking pattern suggests that the deposition of all units occurred progressively, in process of rising relative sea level&nbsp