), respectively, but when given together, 80% of the animals were parasitologically cured. The cured animals showed an absence of myocarditis and a normalisation of cytokine production in the sera. In addition, no in vitro toxicity was observed at the tested doses. Conclusions and implications: These findings indicate that trans-[RuCl([15]aneN4)NO]2+ is a promising lead compound for the treatment of human Chagas' disease.

Altered myocardial perfusion is a common finding in chronic Chagas cardiomyopathy (CCC), but its underlying histologic changes have not been elucidated. We investigated the occurrence of myocardial perfusion defects (MPDs) and the correlated regional changes to histology in an experimental model of CCC in hamsters. Female Syrian hamsters ( = 34) were infected with 3.5 × 10 to 10 trypomastigote forms of Y strain, and 6-10 mo afterward underwent in vivo imaging including restingTc-sestamibi SPECT, segmental and global left ventricular function assessment using 2-dimensional echocardiography, and F-FDG PET for evaluation of myocardial viability. Histologic analysis included quantification of fibrosis, inflammatory infiltration, and the diameter and density of myocardial microcirculation. MPDs were present in 17 (50%) of the infected animals. Histologic analysis revealed no transmural scar in segments with an MPD, and normal or mildly reduced F-FDG uptake, indicating viable myocardium. Infected animals with an MPD, in comparison to infected animals without an MPD and control animals, showed a lower left ventricular ejection fraction ( = 0.012), a higher wall motion score index ( = 0.004), and a higher extent of inflammatory infiltration ( = 0.018) but a similar extent of fibrosis ( = 0.15) and similar microvascular diameter and density ( > 0.05). Segments with an MPD ( = 65), as compared with normally perfused regions in the same animal ( = 156), showed a higher wall motion score index ( = 0.005) but a similar extent of inflammatory infiltration, a similar extent of fibrosis, and a similar microvascular diameter and density. Resting MPDs are frequent in experimental CCC and are associated with myocardial inflammation but do not designate scar tissue, corresponding to regions with metabolically viable myocardium.

BackgroundChagas disease remains a serious medical and social problem in Latin America and is an emerging concern in nonendemic countries as a result of population movement, transfusion of infected blood or organs and congenital transmission. The current treatment of infected patients is unsatisfactory due to strain-specific drug resistance and the side effects of the current medications. For this reason, the discovery of safer and more effective chemotherapy is mandatory for the successful treatment and future eradication of Chagas disease.Methods and FindingsWe investigated the effect of a ruthenium complex with benznidazole and nitric oxide (RuBzNO2) against Trypanosoma cruzi both in vitro and in vivo. Our results demonstrated that RuBzNO2 was more effective than the same concentrations of benznidazole (Bz) in eliminating both the extracellular trypomastigote and the intracellular amastigote forms of the parasite, with no cytotoxic effect in mouse cells. In vivo treatment with the compound improved the survival of infected mice, inhibiting heart damage more efficiently than Bz alone. Accordingly, tissue inflammation and parasitism was significantly diminished after treatment with RuBzNO2 in a more effective manner than that with the same concentrations of Bz.ConclusionsThe complexation of Bz with ruthenium and nitric oxide (RuBzNO2) increases its effectiveness against T. cruzi and enables treatment with lower concentrations of the compound, which may reduce the side effects of Bz. Our findings provide a new potential candidate for the treatment of Chagas disease.

A dramatização teatral “O Julgamento da Mutação” discute se a Mutação é vilã, fonte de patologias ou se é a mocinha, indispensável para a evolução das espécies, tendo como advogada de defesa a Seleção Natural e o promotor, o gene TP53. A partir dos depoimentos das testemunhas, vários conceitos de Genética são abordados contribuindo para a compreensão do que é mutação e principalmente de seu papel para os seres vivos. Entre as testemunhas estão: Célula-Mãe, Célula-Filha, Enzimas de Reparo, Mutantes, tataraneto de Mendel, Evolução e uma Cientista renomada da área. A decisão final caberá à plateia. [...]

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