Advances in preclinical approaches to Chagas disease drug discovery

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Source: Expert Opinion on Drug Discovery - Category: Drugs & Pharmacology Authors: Source Type: research

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HIF-1α and CD73 expression in cardiac leukocytes correlates with the severity of myocarditis in end-stage Chagas disease patients. J Leukoc Biol. 2020 May 25;: Authors: Eberhardt N, Sanmarco LM, Bergero G, Favaloro RR, Vigliano C, Aoki MP Abstract Chronic Chagas cardiomyopathy is the main infectious myocarditis worldwide. Almost 30% of Trypanosoma cruzi infected individuals develop slow and progressive myocarditis that leads to ventricular dilation and heart failure. Heart transplantation is an established, valuable therapeutic option for end-stage Chagas disease patients. Although the pathophys...
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Tags: J Leukoc Biol Source Type: research
In this study, we aimed to evaluate rLiNTPDase2-ELISA in a Phase II study with 651 dog sera samples, also comparing it with methodologies previously established and used in epidemiology surveillance in Brazil, an endemic country of CVL and VL. The rLiNTPDase2-ELISA using standard control sera showed high capability to distinguish between positive and negative sera, sensitivity of 92.6% and specificity of 88.5%. The test was reproductive and the kappa statistics judgement "substantial agreement". rLiNTPDase2-ELISA does not show cross-reactivity with ehrlichiosis-reagent sera. However, we verified 15.3% of cross-re...
Source: Acta Tropica - Category: Infectious Diseases Authors: Tags: Acta Trop Source Type: research
Calanolides E1 and E2, two related coumarins from Calophyllum brasiliense Cambess. (Clusiaceae), displayed in vitro activity against amastigote forms of Trypanosoma cruzi and Leishmania infantum. Nat Prod Res. 2020 May 22;:1-5 Authors: Silva LG, Gomes KS, Costa-Silva TA, Romanelli MM, Tempone AG, Sartorelli P, Lago JHG Abstract In the present work, the MeOH extract from stem barks of Calophyllum brasiliense Cambess. (Clusiaceae) displayed activity against amastigote forms of Trypanosoma cruzi and Leishmania infantum and was subjected to a bioactivity-guided fractionation to give two related couma...
Source: Natural Product Research - Category: Biochemistry Authors: Tags: Nat Prod Res Source Type: research
RV, Diniz LF, Novaes RD Abstract While thioridazine (Tio) inhibits the antioxidant defenses of Trypanosoma cruzi, the gold standard antitrypanosomal drug benznidazole (Bz) has potent anti-inflammatory and pro-oxidant properties. The combination of these drugs has never been tested to determine the effect on T. cruzi infection. Thus, we compared the impact of Tio and Bz, administered alone and in combination, on the development of skeletal myositis and liver inflammation in T. cruzi-infected mice. Swiss mice were randomized into six groups: uninfected untreated, infected untreated, treated with Tio (80 mg/kg) ...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
by Jacob M. Wozniak, Tatiana Ara újo Silva, Diane Thomas, Jair L. Siqueira-Neto, James H. McKerrow, David J. Gonzalez, Claudia M. Calvet Chagas disease, the clinical presentation of aT.cruzi infection, is a major human health concern. While the acute phase of Chagas disease is typically asymptomatic and self-resolving, chronically infected individuals suffer numerous sequelae later in life. Cardiomyopathies in particular are the most severe consequence of chronic Chagas disease and cannot be reversed solely by parasite load reduction. To prioritize new therapeutic targets, we unbiasedly interrogated the host signal...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Chagas disease is a major public health issue, affecting ~10 million people worldwide. Transmitted by a protozoan named Trypanosoma cruzi, this infection triggers a chronic inflammatory process that can lead to cardiomyopathy (Chagas disease). Resolvin D1 (RvD1) is a novel proresolution lipid mediator whose effects on inflammatory diseases dampens pathological inflammatory responses and can restore tissue homeostasis. Current therapies are not effective in altering the outcome of T. cruzi infection, and as RvD1 has been evaluated as a therapeutic agent in various inflammatory diseases, we examined if exogenous RvD1 could m...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Fungal and Parasitic Infections Source Type: research
Population genetics of two chromatic morphs of the Chagas disease vector Rhodnius pallescens Barber, 1932 in Panamá. Infect Genet Evol. 2020 May 19;:104369 Authors: Kieran TJ, Bayona-Vásquez NJ, Varian CP, Saldaña A, Samudio F, Calzada JE, Gottdenker NL, Glenn TC Abstract Rhodnius pallescens is the principal vector of Chagas disease in Panama. Recently a dark chromatic morph has been discovered in the highlands of Veraguas Province. Limited genetic studies have been conducted with regards to the population structure and dispersal potential of Triatominae vectors, particularly in R...
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research
In this study, we evaluated the effect of ravuconazole, an EBI, combined with amlodipine, a calcium channel blocker, upon T. cruzi experimental infection. In vitro assays confirmed the trypanocidal activity of both compounds in monotherapy and demonstrated an additive effect (∑FIC>0.5) of the combined treatment without additional toxicity to host cells. In vivo experiments, using a murine model of the T. cruzi Y strain in a short-term protocol, demonstrated that amlodipine, although lacking trypanocidal activity, dramatically increased the anti-parasitic activity of underdosing ravuconazole regimens. Additional anal...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract Chronic Chagas disease can progress to myocardial involvement with intense fibrosis, which may predispose patients to sudden cardiac death through ventricular arrhythmia. The associations of myocardial fibrosis detected by cardiac magnetic resonance (CMR) parameters with non-sustained ventricular tachycardia (NSVT) were evaluated. This cross-sectional study included patients in early stages of Chagas disease (n = 47) and a control group (n = 15). Patients underwent cardiac evaluation, including CMR examination. Myocardial fibrosis assessment by CMR with measurement of late gadolinium enhancement (LGE), na...
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
ijalva MJ, Brenière SF Abstract Rhodnius ecuadoriensis is one of the most important vector species of Chagas disease in Ecuador. This species is distributed in the Central coast region and in the south Andean region, and an incipient speciation process between these geographical populations was previously proposed. The current population genetics study only focused on the Central coast region and analyzed 96 sylvatic specimens of R. ecuadoriensis associated with Phytelephas aequatorialis palm trees. We used Cytb and 16S-rRNA sequences and a Cytb-16S-rRNA concatenated set to explore (i) the genetic variabili...
Source: Acta Tropica - Category: Infectious Diseases Authors: Tags: Acta Trop Source Type: research
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