Blocking central leukotrienes synthesis affects vasopressin release during sepsis

Recent studies revealed that vasopressinergic neurons have a high content of cys-leukotriene C(4) (LTC(4)) synthase, a critical enzyme in cys-leukotriene synthesis that may play a role in regulating vasopressin secretion. This study investigates the role of this enzyme in arginine vasopressin (AVP) release during experimentally induced sepsis. Male Wistar rats received an i.c.v. injection of 3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl]-2, 2-dimethylpropanoic acid (MK-886) (1.0 mu g/kg), a leukotrienes (LTs) synthesis inhibitor, or vehicle, 1 h before cecal ligation and puncture (CLP) or sham operation. In one group of animals the survival rate was monitored for 3 days. In another group, the animals were decapitated at 0, 4, 6, 18 and 24 h after CLP or sham operation, and blood was collected for hematocrit, serum sodium and nitrate, plasma osmolality, protein and AVP determination. A third group was used for blood pressure measurements. The neurohypophysis was removed for quantification of AVP content, and the hypothalamus was dissected for LTC4 synthase analysis by Western blot. Mortality after CLP was reduced by the central administration of MK-886. The increase in plasma AVP levels and hypothalamus LTC4 synthase content in the initial phase of sepsis was blocked, whereas the decrease in neurohypophyseal AVP content was partially reversed. Also the blood pressure drop was abolished in this phase. The increase of serum nitric oxide and hematocrit was reduced, and the decrease in plasma protein and osmolality was not affected by the LTs blocker. In the final phase of sepsis, the plasma AVID level and the hypothalamic LTC4 synthase content were at basal levels. The central administration of MK-886 increased the hypothalamic LTC4 synthase content but did not alter the plasma and neurohypophysis AVID levels observed, or the blood pressure during this phase. These results suggest that the central LTs are involved in the vasopressin release observed during sepsis. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved

Chaetoglobosins produced by Chaetomium globosum, endophytic fungus found in association with Viguiera robusta Gardn (Asteraceae)

Endophytes live in association with host plants during all or part of their life cycle without causing any apparent disease. They are considered outstanding and underexploited sources of novel bioactive compounds. Chaetomium globosum was isolated as an endophytic fungus from the healthy leaves of Viguiera robusta. C.globosum is a remarkable producer of chaetoglobosins, which are typically cytotoxic. In this work, chaetoglobosins B (1), D (2) and E (3) have been produced by the endophytic C. globosum strain. Chaetoglobosin B was evaluated against Jurkat (leukemia) and B16F10 (melanoma) tumoral cells and showed 89.55% and 57.10% of inhibition at 0.1 mg mL-1, respectively. Chaetoglobosin B also showed weak antibacterial activity against Staphylococcus aureus (MIC 120 µg/mL) and Escherichia coli (MIC 189 µg/mL).Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Chemical constituents from Tabernaemontana catharinensis root bark: a brief NMR review of indole alkaloids and in vitro cytotoxicity

This work describes the isolation and structural determination of pharmacological compounds present in the bark of roots of Tabernaemontana catharinensis (Apocynaceae). Among the 27 substances detected 12 were identified as terpenoid-indole alkaloids, 2 steroids and 13 pentacyclic triterpenes. Structures were outlined based on HMQC, COSY, DEPT, 13C, and ¹H NMR data and MS. Spectral data of indole alkaloids were reviewed. An in vitro screening of the extracts and isolated compounds was carried out. Compounds ibogamine (5), 3-oxo-coronaridine (9) and 12-methoxy-4-methylvoachalotine (MMV) demonstrated effective cytotoxicity towards SKBR-3 breast adenocarcinoma and C-8161 human melanoma tumor cell lines.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)UNAER

Promoção de saúde e cidadania através de práticas grupais com adolescentes

Trabalho apresentado no II Congresso Nacional do PROJETO RONDON, realizado em Florianópolis, SC, no período de 23 a 25 de setembro de 2015 - Universidade Federal de Santa Catarina.Objetivo: apresentar e discutir práticas grupais interativas realizadas com adolescentes e jovens do município de São Mateus do Maranhão – MA, durante a Operação Jenipapo do Projeto Rondon. Método: foi realizado um ciclo de oficinas interativas com debates, rodas de conversa e exposições educativas e informativas ao longo de duas semanas, das quais participaram cerca de 40 adolescentes e jovens das zonas rural e urbana do município de São Mateus - MA. As oficinas visavam conscientizar e introduzir as temáticas relacionadas à sexualidade, planejamento familiar, prevenção de DSTs e de uso de substâncias psicotrópicas; introduzir conceitos de cidadania, meios de acesso à justiça e meios para sua concretização; debater possibilidades de inserção profissional e planejamento de vida; além de incentivar a reflexão e elaboração de possibilidades concretas para uma atuação ativa em sua comunidade. As atividades eram conduzidas por alunos rondonistas a partir de uma pauta temática previamente elaborada, sendo que os participantes poderiam intervir ativamente. Os materiais utilizados incluíam recursos informativos, explicativos, cartazes, vídeos e multimídia. Resultados: De acordo com a percepção dos adolescentes, após as oficinas, houve uma melhora na compreensão de todas as temáticas abordadas, sendo que as questões que mais mobilizaram a participação e interesse dos adolescentes foi relacionado à sexualidade e planejamento de vida. As atividades também mobilizaram os participantes para a proposição e organização coletiva de ideias que tivessem implicações práticas na própria comunidade. Conclusão: as oficinas desenvolvidas foram bem recebidas e permitiram aos participantes ampliar seus conhecimentos, responder aos questionamentos e dúvidas que apresentavam sobre os conteúdos abordados, evidenciando que as práticas grupais relatadas podem ser efetivamente implementadas em novas Operações do Projeto Rondon, a fim de promover saúde, educação e incentivar a consciência cidadã para a juventude brasileira em diferentes contextos

Biological activities from extracts of endophytic fungi isolated from Viguiera arenaria and Tithonia diversifolia

A total of 39 endophytic fungi have been isolated from Viguiera arenaria and Tithonia diversifolia, both collected in São Paulo State, Brazil. The isolates were identified based on their ribosomal DNA sequences. The ethyl acetate (EtOAc) extracts of all endophytic fungi were evaluated for their antimicrobial, antiparasitic and antitumoral activity. Antimicrobial screening was conducted using an agar diffusion assay against three pathogenic microorganisms: Staphylococcus aureus, Escherichia coli and Candida albicans. Antiparasitic activity was determined by enzymatic inhibition of gGAPDH of Trypanosoma cruzi and adenine phosphorybosiltransferase (APRT) of Leishmania tarentolae. Antitumoral activity was tested against human T leukemia cells by the Mosmann colorimetric method. All extracts showed activity in at least one assay: 79.5% of the extracts were cytotoxic against leukemia cells, 5.1% of the extracts were active against S. aureus, 25.6% against E. coli and 64.1% against Candida albicans. Only one extract showed promising results in the inhibition of parasitic enzymes gGAPDH (95.0%) and three were found to inhibit APRT activity. The cytotoxic extract produced by the strain VA1 (Glomerella cingulata) was fractionated and yielded nectriapyrone and tyrosol. Nectriapyrone showed relevant cytotoxic activity against both human T leukemia and melanoma tumor cell lines.FAPESP 03/07535-5FAPESP 04/07935-6CAPE

The Acute Phase of Trypanosoma cruzi

In the present work we examine the contribution of 5-lipoxygenase- (5-LO-) derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO−/−) mice and wild-type (WT) mice. Compared with WT mice, the 5-LO−/− mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO−/− mice correlated with several differences in the immune response to infection, including reduced PGE2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL)-12 early in the infection; enhanced splenocyte production of IL-1β, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8+CD44highCD62Llow memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection

Caracterização morfologica e funcional de exsudato peritoneal induzido pela jacalina em camundongos

Orientador: Antonio Campos NetoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: Neste trabalho, estudamos o exsudato peritoneal em camundongos induzido pela lectina jacalina. Nós observamos que a jacalina induz grande influxo de células polimorfo nucleares (neutrófilos) nas primeiras 48 horas. Após esse período, o número de neutrófilos regride e o número de células mononucleares aumenta. As células mononucleares atingem a níveis máximos 72-96 h, após a injeção de jacalina. Aproximadamente 78% das células mononucleares são macrófagos quando analizadas pelo ensaio de esterase não-específica. As análises funcionais destes macrófagos mostram que grande parte dessas células expressam receptores para Fcy (85%) e C3b (91%), fagocitam particular através dessas vias (90% para Fc e 91% via C3b), expressam moléculas Ia (59%), apresentam antígenos para linfócitos T de animais sensibilizados com KLH e secretam IL-1, após estimulação com LPS e H2O2, após estimulação com PMA. Interessantemente, estas células não secretam FNT após estimulação com LPS. Nós demonstramos ainda que a Jacalina estimula a secreção de H2O2 em macrófagos inflamatórios (Com-A e jacalina), mas não FNT ou IL-1.Estes resultados indicam que a jacalina é um excelente agente para a indução de exsudato peritoneal de camundongos ricos em macrófagos com importantes atividades funcionais e que ¿in vitro¿ é capaz de ativar uma via metabólica seletiva nos macrófagos. ...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digitalAbstract: In this work we studied the peritoneal exsudate induced by the lectin jacalin. We observed that jacalin induced large numbers of Polymorphonuclear cells (Neutrophils) within a 48 h period. After this time, the number of neutrophils decreased and the number of mononuclear cells increased. Following injection with jacalin, the number of mononuclear cells reached a maximum level within 72-96 h. Approximately 78% of the mononuclear cells were macrophages which tested positive for the non-specific esterase assay. The functional analysis of these macrophages shows that a large number of these cells express Fc gamma (85%) and C3b (91%) receptors, phagocytize particles coated with the relevant opsonins (90% to Fc and 91% to C3b), express Ia molecules (59%), present antigens to KLH-sensitized T cells and secrete IL-1 after stimulation with LPS and H2O2 after stimulation with PMA. Iterestingly, these cells did not secrete TNF after stimulation with LPS. We also demonstrated that jacalin stimulates the secretion of H2O2 in elicited peritoneal macrophages, but not IL-1 or TNF. These results indicate that jacalin is an excellent agent for the induction of peritoneal exsudate cells rich in macrophages with important effector fctions and that ¿in vitro¿ it can trigger selective metabolic phathways in macrophages. ...Note: The complete abstract is available with the full electronic digital thesis or dissertationsMestradoImunologiaMestre em Ciências Biológica

NK1.1 cells are required to control T cell hyperactivity during Trypanosoma cruzi infection.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-18T12:17:42Z No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-18T13:03:27Z (GMT) No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5)Made available in DSpace on 2015-06-18T13:03:27Z (GMT). No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5) Previous issue date: 2004University of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, Brasil / University of São Paulo. Department of Clinical Analysis. São Paulo, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Doença Experimental de Chagas, Imunologia Celular e Auto-imunidade. Salvador, BA, BrasilUniversity of São Paulo. Department of Clinical Analysis. São Paulo, SP, BrasilUniversity of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, BrasilUniversity of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, Brasil / University of São Paulo. Department of Clinical Analysis. São Paulo, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Doença Experimental de Chagas, Imunologia Celular e Auto-imunidade. Salvador, BA, BrasilBACKGROUND: This study evaluated the regulatory function of NK1.1+ cells during Trypanosoma cruzi infection. MATERIAL/METHODS: Both thymectomized (Tx C57Bl/6) and euthymic C57Bl/6 mice (C57Bl/6) were infected intraperitoneally with the Tulahuen strain. NK1.1+ cells were depleted in vivo by anti-NK1.1 mAb. Spleen cells were analyzed by flow cytometry for the expression of CD44 and CD69 on T cells. Supernatants from splenocytes were used to measure nitrite concentration (quantified by Griess reagent). Interleukin 2 and IFN-gamma levels were determined by ELISA. The protocols used herein were approved by the Institutional Committee for Ethics. Student's t or Kruskal-Wallis tests were applied, as indicated. RESULTS: The number of T cells expressing CD69 increased progressively during T. cruzi infection in NK1.1 cell-depleted C57Bl/6 mice. In spite of an increased early T cell activation during infection, the percentage of CD4+ CD44high T cells did not augment in NK1.1 cell-depleted C57Bl/6 mice compared with untreated C57Bl/6 controls. Serum levels of IFN-gamma in anti-NK1.1-treated mice were higher than in non-depleted animals. Con-A-stimulated spleen cell supernatants from NK1.1 cell-depleted animals contained increased levels of IL-2 and nitric oxide (NO) during early infection. CONCLUSIONS: After the first week of infection, NO overproduction and high levels of IFN-gamma in anti-NK1.1-tre-ated C57Bl/6 mice appeared to be related to susceptibility and hyperactivation of peripheral T cells. Finally, this study suggests a novel regulatory function of NK1.1+ cells during T. cruzi infection. Without NK1.1 cells, T lymphocytes are hyperactivated but do not differentiate to effector/memory T cells in infected C57Bl/6 mice