Chagas Disease: Progress and New Perspectives

Sánchez-Sancho, Francisco; Campillo, Nuria E.; Páez, Juan A.

doi:10.2174/092986710790226101

Cited by 50 publications

(32 citation statements)

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“…cruzi (494). In recent years, Chagas' disease has become a public health concern in countries where the disease is not endemic due to immigration from areas where the disease is endemic (293,294,502,601,615).…”

Section: Trypanosomamentioning

confidence: 99%

Importance of Nonenteric Protozoan Infections in Immunocompromised People

et al. 2010

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SUMMARY There are many neglected nonenteric protozoa able to cause serious morbidity and mortality in humans, particularly in the developing world. Diseases caused by certain protozoa are often more severe in the presence of HIV. While information regarding neglected tropical diseases caused by trypanosomatids and Plasmodium is abundant, these protozoa are often not a first consideration in Western countries where they are not endemic. As such, diagnostics may not be available in these regions. Due to global travel and immigration, this has become an increasing problem. Inversely, in certain parts of the world (particularly sub-Saharan Africa), the HIV problem is so severe that diseases like microsporidiosis and toxoplasmosis are common. In Western countries, due to the availability of highly active antiretroviral therapy (HAART), these diseases are infrequently encountered. While free-living amoebae are rarely encountered in a clinical setting, when infections do occur, they are often fatal. Rapid diagnosis and treatment are essential to the survival of patients infected with these organisms. This paper reviews information on the diagnosis and treatment of nonenteric protozoal diseases in immunocompromised people, with a focus on patients infected with HIV. The nonenteric microsporidia, some trypanosomatids, Toxoplasma spp., Neospora spp., some free-living amoebae, Plasmodium spp., and Babesia spp. are discussed.

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Section: Trypanosomamentioning

confidence: 99%

Importance of Nonenteric Protozoan Infections in Immunocompromised People

et al. 2010

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“…Compounding this scenario, the available chemotherapy for Chagas' disease is unsatisfactory (Castillo et al 2010). Therefore, novel anti-T. cruzi drugs, ideally directed against new parasite targets, are urgently needed (Sánchez-Sancho et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

et al. 2011

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Herein, we have aimed to explore the effects of pepstatin A, a powerful aspartic protease inhibitor, on Trypanosoma cruzi, the etiologic agent of Chagas' disease. Pepstatin A arrested the proliferation of epimastigotes of T. cruzi (clone Dm28c, TcI lineage), in both dose- and time-dependent manner. The IC(50) value was calculated to be 36.2 μM after 96 h of parasite-drug contact. The parasite treatment with pepstatin A resulted in significant morphological alterations, including parasites becoming round in shape, reduction (≈25%) of the parasite size, and parasites presenting parts or the whole flagellum detached from the cell body. Cell lysis was not observed, resulting in a trypanostatic effect. The treatment of different T. cruzi strains, belonging to distinct phylogenetic lineages, with pepstatin A at 36.2 μM resulted in growth inhibition as follows: 28% to Y (TcII), 45% to CL Brener (TcII), 45.4% to 4167 (Z3), and 26.4% to 3663 (Z3) strains. The hydrolysis of a cathepsin D fluorogenic substrate (7-methoxycoumarin-4-acetyl-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-D: -Arg-amide) by T. cruzi epimastigote extract was inhibited (≈65%) by pepstatin A at 10 μM, suggesting that an aspartic protease may be the intracellular target of this inhibitor. Curiously, pepstatin A induced an increase of 54% and 98%, respectively, in the surface expression of gp63- and calpain-related molecules in epimastigotes, but not in the cruzipain level, as well as stimulated the epimastigote-to-trypomastigote differentiation in a dose-dependent manner. However, approximately 45% of the trypomastigotes had their flagellum detached from the cell body. These results contribute to understand the possible role of aspartic proteases in the physiology of T. cruzi cells, adding new in vitro insights into the possibility of exploiting aspartic protease as promising targets to treat Chagas' disease.

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“…A further 100 million are at risk of infection. At any one time around 2-3 million individuals show clinical symptoms of the chronic phase of the disease and 45000 people die each year (1)(2)(3). The only drugs approved for the treatment of Chagas' disease, nifurtimox and benznidazole, were introduced for therapeutic use over thirty years ago.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Glycans, Glycoarrays, and Glyconanoparticles To Investigate Host Infection byTrypanosoma cruzi

Field

Andrade

Campo

et al. 2011

ACS Symposium Series

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Carbohydrate libraries, synthetic glycans and glycopeptides are contributing to understanding of the role of sialic acid recognition in host infection by the parasite Trypanosoma cruzi. Further, glycoarray approaches are allowing us to explore similarities and differences in the carbohydrate-binding specificity of host lectins while glyconanoparticles enable us to ask questions about the structure, sialylation and recognition of parasite mucins.

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Chagas Disease: Progress and New Perspectives

Cited by 50 publications

References 0 publications

Importance of Nonenteric Protozoan Infections in Immunocompromised People

Importance of Nonenteric Protozoan Infections in Immunocompromised People

Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

Synthetic Glycans, Glycoarrays, and Glyconanoparticles To Investigate Host Infection byTrypanosoma cruzi

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