Chagas disease is a relevant public health threat that affects over 6 million people worldwide, resulting in devastating social and economic consequences. Moreover, the therapeutic options are limited, highlighting the urgency in searching for novel active antitrypanosomal molecules. Compounds with either thiazole or biaryl units have been described as possessing anti Trypanosoma cruzi activities. Therefore, here, we describe the synthesis of nine arylated and diarylated thiazole derivatives and the evaluation of their in vitro toxicity on mammalian cells as well as their anti T. cruzi activity. The compounds were prepared in straightforward synthetic routes, using Hantzsch thiazole synthesis and cross-coupling reactions as key steps. A pyridyl-phenyl-thiazole (PPT) derivative (4c) presented 76% of T. cruzi growth inhibition in preliminary tests using a fixed concentration of 20 µM. This compound was used as a scaffold for the synthesis of two novel PPT analogs (4g and 4h). Dose-response assays on intracellular forms of T. cruzi demonstrated that these three compounds presented high antiparasitic potency (half maximal effective concentration (EC50) values ranging from 1.15 to 2.38 μM) and low toxic profile against L929 cell lines. Hence, these findings highlight the pyridyl-phenyl-thiazole backbone as a novel privileged scaffold in the search for active molecules against T. cruzi.

Copper(II) complexes of the Schiff base ligands 2-((5-nitrofuran-2-yl)methyleneamino)phenol (HL1) and 2-(4-nitrobenzylideneamino)phenol (HL2) were prepared and characterized using physicochemical and spectroscopic techniques. In these complexes the Schiff base ligands acted as a bidentate donor bound to Cu2+ through the oxygen and nitrogen atoms in the deprotonated form. The electron paramagnetic resonance spectra, carried out on [CuCl(L1)(phen)].0.5H2O and [CuCl(L2)(phen)].2H2O complexes, showed the presence of only mononuclear forms. The Cu2+ complexes and ligands were evaluated for their in vitro trypanocidal activity. The complex [CuCl(L1)(phen)].0.5H2O was more active than the free Schiff base and also presented a superior effect to benznidazole, the reference drug. The antiproliferative activity of the Schiff bases and Cu2+ complexes were evaluated for their effect on seven tumor cell lines and showed a cytostatic and in some cases a cytotoxic effect. These compounds also presented binding properties to deoxyribonucleic acid (DNA) and moderate ability to quench the intrinsic fluorescence of albumins.

O presente artigo apresenta as etapas de estruturação do Programa de Capacitação Profissional de Biossegurança (PCPB), em consonância com o Projeto de Modernização da Gestão Científica do Instituto Oswaldo Cruz (IOC), detalhando o ciclo planejamento-desenvolvimento-avaliação, em especial do Curso de Biossegurança em Laboratório de Pesquisa Biomédica. Inicialmente, para o ciclo diagnóstico foram aplicados questionários aos interlocutores dos laboratórios do IOC, os quais revelaram interesse de participação no PCPB para ambas as categorias profissionais (níveis médio e superior), indicando como temáticas preferenciais biossegurança e boas práticas de laboratório. Na fase de planejamento foi definido que o PCPB seria subdivido em dois projetos (Boas Práticas de Laboratório de Saúde Pública para os profissionais de nível médio e Curso de Biossegurança para Laboratórios de Pesquisa Biomédica para profissionais de nível superior). A seguir, na fase de estruturação do curso, os módulos contemplados incluíram: introdutório; riscos químico, físico e biológico; gestão da qualidade e experimentação animal. Assim, no período 2006-2008, foram capacitados 315 profissionais e realizadas avaliações segundo o modelo de David Kirkpatrick. O primeiro nível, chamado de reação, foi aferido e demonstrou que 54,03% dos profissionais declararam que o curso foi excelente; 39,59% classificaram como bom e os demais 6,38% acharam que foi regular ou não opinaram. Para a avaliação do aprendizado foram realizados, a cada módulo, pré e pós-testes. Foi verificado que todos os módulos tiveram acréscimos nas médias do pós-teste em relação ao pré-teste. Os resultados obtidos apontaram estratégias a serem seguidas no aperfeiçoamento desse modelo de educação continuada em biossegurança.

In the present paper we report a Biosafety Training Program (BTP) developed at Oswaldo Cruz Institute (IOC/Fiocruz) aligned with the Scientific Management Modernization Project of IOC. The program, including the "Biosafety Course in Biomedical Research Laboratory", was structured according to the planning-development-evaluation cycle. Initially, for the diagnosis cycle, the IOC laboratories representatives answered a questionnaire that showed that both professional categories (middle and higher levels) were interested in participating in BTP and mentioned, as preferential themes, biosafety and good laboratory practices. In the planning phase it was defined that BTP would be divided into two projects (Good Laboratory Practices in Public Health for middle level professionals and Biosafety Course in Biomedical Research Laboratories for higher level professionals). During the development phase of the Biosafety Course, the following modules were chosen: introduction, chemical, physical and biological risks, quality management and animal experimentation. Thus, in the period from 2006 to 2008, 315 professionals were trained and the respective evaluations were performed according to David Kirkpatrick's model. The first level of evaluation, called reaction, showed that 54.03% of the professionals said that the course was excellent, 39.59% classified the course as good and 6.38% as regular or did not express any opinion. For learning evaluation, pre and post-tests were carried out in each module. All the modules showed an increase in the grades of the post-test when compared to the pre-test. The results pointed to strategies that should be followed in order to improve this biosafety continuing education model.

O presente artigo apresenta as etapas de estruturação do Programa de Capacitação Profissional de Biossegurança (PCPB), em consonância com o Projeto de Modernização da Gestão Científica do Instituto Oswaldo Cruz (IOC), detalhando o ciclo planejamento-desenvolvimento-avaliação, em especial do Curso de Biossegurança em Laboratório de Pesquisa Biomédica. Inicialmente, para o ciclo diagnóstico foram aplicados questionários aos interlocutores dos laboratórios do IOC, os quais revelaram interesse de participação no PCPB para ambas as categorias profissionais (níveis médio e superior), indicando como temáticas preferenciais biossegurança e boas práticas de laboratório. Na fase de planejamento foi definido que o PCPB seria subdivido em dois projetos (Boas Práticas de Laboratório de Saúde Pública para os profissionais de nível médio e Curso de Biossegurança para Laboratórios de Pesquisa Biomédica para profissionais de nível superior). A seguir, na fase de estruturação do curso, os módulos contemplados incluíram: introdutório; riscos químico, físico e biológico; gestão da qualidade e experimentação animal. Assim, no período 2006-2008, foram capacitados 315 profissionais e realizadas avaliações segundo o modelo de David Kirkpatrick. O primeiro nível, chamado de reação, foi aferido e demonstrou que 54,03% dos profissionais declararam que o curso foi excelente; 39,59% classificaram como bom e os demais 6,38% acharam que foi regular ou não opinaram. Para a avaliação do aprendizado foram realizados, a cada módulo, pré e pós-testes. Foi verificado que todos os módulos tiveram acréscimos nas médias do pós-teste em relação ao pré-teste. Os resultados obtidos apontaram estratégias a serem seguidas no aperfeiçoamento desse modelo de educação continuada em biossegurança.

In the present paper we report a Biosafety Training Program (BTP) developed at Oswaldo Cruz Institute (IOC/Fiocruz) aligned with the Scientific Management Modernization Project of IOC. The program, including the "Biosafety Course in Biomedical Research Laboratory", was structured according to the planning-development-evaluation cycle. Initially, for the diagnosis cycle, the IOC laboratories representatives answered a questionnaire that showed that both professional categories (middle and higher levels) were interested in participating in BTP and mentioned, as preferential themes, biosafety and good laboratory practices. In the planning phase it was defined that BTP would be divided into two projects (Good Laboratory Practices in Public Health for middle level professionals and Biosafety Course in Biomedical Research Laboratories for higher level professionals). During the development phase of the Biosafety Course, the following modules were chosen: introduction, chemical, physical and biological risks, quality management and animal experimentation. Thus, in the period from 2006 to 2008, 315 professionals were trained and the respective evaluations were performed according to David Kirkpatrick's model. The first level of evaluation, called reaction, showed that 54.03% of the professionals said that the course was excellent, 39.59% classified the course as good and 6.38% as regular or did not express any opinion. For learning evaluation, pre and post-tests were carried out in each module. All the modules showed an increase in the grades of the post-test when compared to the pre-test. The results pointed to strategies that should be followed in order to improve this biosafety continuing education model.

We herein present an improved assay for detecting the presence of Trypanosoma cruzi in infected cultures. Using chagasic human sera (CHS), we were able to detect T. cruzi infection in primary cultures of both peritoneal macrophages and heart muscle cells (MHC). To avoid elevated background levels - hitherto observed in all experiments especially in those using HMC - CHS were preincubated with uninfected cells in monolayers or suspensions prior to being used for detection of T. cruzi in infected monolayers. Preincubation with cell suspensions gave better results than with monolayers, reducing background by up to three times and increasing sensitivity by to twenty times. In addition, the continous fibroplastic cell line L929 was shown to be suitable for preadsorption of CHS. These results indicate that the high background levels observed in previous reports may be due to the presence of human autoantibodies that recognize surface and/or extracellular matrix components in cell monolayers. We therefore propose a modified procedure that increases the performance of the ELISA method, making it an useful tool even in cultures that would otherwise be expected to present low levels of infection or high levels of background

Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and,to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxity between anti-trypanossomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypothesis for the mechanism of action of phenothiazines are discussed.