Trypanosoma cruzi: The effects of zinc supplementation during experimental infection
Vânia BrazãoMarina Del Vecchio FilipinLeony Cristina CaetanoMíriam Paula Alonso ToldoLuana Naiara CaetanoJosé Clóvis do Prado Júnior
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Chagas Disease
Benznidazole
Chagas Disease
Nifurtimox
Nitazoxanide
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Germfree (GF) and conventional (CV) CFW (LOB) mice and Wistar and Sprague-Dawley rats were infected with Trypanosoma cruzi. The disease was more severe in the GF than in the CV animals as revealed by: (1) an earlier and more intense parasitemia; (2) a more precocious mortality; (3) a twice enlarged spleen: (4) a more intense cell and tissue parasitism; (5) visceral signs of cardiac failure.
Chagas Disease
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Chagas disease is
caused by the protozoan parasite Trypanosoma
cruzi. It is endemic in South and Central America and recently
has been found in other parts of the world, due to migration of chronically
infected patients. The current treatment for Chagas disease is not
satisfactory, and there is a need for new treatments. In this work,
we describe the optimization of a hit compound resulting from the
phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory
pharmacokinetics to allow an efficacy study in a mouse model of Chagas
disease. We were able to demonstrate efficacy in this model, although
further work is required to improve the potency and selectivity of
this series.
Chagas Disease
Phenotypic screening
Protozoan parasite
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Chagas disease is caused by the parasite protozoan Trypanosoma cruzi (T. cruzi) and affects millions of people in over 21 countries in around the world. The main forms of treatment of this disease, benznidazole and nifurtimox, present low cure rates in the chronic phase and often have serious side effects. Herein, we describe the evaluation of the trypanocidal activity of arylsulfonamides. The arylsulfonamides were evaluated in vitro against the amastigote and trypomastigote forms of the parasite. An enantiomerically pure example of arylsulfonamide was also tested. The initial results suggest that the arylsulfonamides evaluated act as DNA binding agents. A moderate activity was monitored against the intracellular forms of T. cruzi, with the best compound exhibiting an IC50 value at 22 μM and a selectivity index of 120. However, the level of activity was not favorable for progressing towards in vivo studies for Chagas disease.
Benznidazole
Chagas Disease
Amastigote
Nifurtimox
Trypanocidal agent
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Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in South and Central America and recently has been found in other parts of the world, due to migration of chronically infected patients. The current treatment for Chagas disease is not satisfactory, and there is a need for new treatments. In this work, we describe the optimization of a hit compound resulting from the phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory pharmacokinetics to allow an efficacy study in a mouse model of Chagas disease. We were able to demonstrate efficacy in this model, although further work is required to improve the potency and selectivity of this series.
Chagas Disease
Trypanocidal agent
Nifurtimox
Kinetoplastida
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Chagas Disease
Kinetoplastida
Xenodiagnosis
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As soon as they were published early in 1909, Chagas's articles on Trypanosoma cruzi and American trypanosomiasis became the topic of discussions in France. The description of T. cruzi and Chagas disease was added to parasitology textbooks as early as 1912, and elicited active research, particularly on the part of French parasitologist Emile Brumpt. He contributed towards eluciding the lifecycle of T. cruzi and the different ways it could infect humans. Laboratory research on T. cruzi was interrupted by First World War and was not resumed afterwards on the same scale, although interest in the epidemiology of Chagas disease continued.
Chagas Disease
Parasitology
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Chagas Disease
clone (Java method)
Infectivity
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Benznidazole
Chagas Disease
Nifurtimox
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Benznidazole
Chagas Disease
Amastigote
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