Drug Repurposing in Chagas Disease: Chloroquine Potentiates Benznidazole Activity against Trypanosoma cruzi and .

Drug combinations and drug repurposing have emerged as promising strategies to develop novel treatments for infectious diseases, including Chagas disease. In this study, we aimed to investigate whether the repurposed drugs chloroquine (CQ) and colchicine (COL), known to inhibit Trypanosoma cruzi infection in host cells, could boost the anti-T. cruzi effect of the trypanocidal drug benznidazole (BZN), increasing its therapeutic efficacy while reducing the dose needed to eradicate the parasite.

Mapping benznidazole resistance in trypanosomatids and exploring evolutionary histories of nitroreductases and ABCG transporter protein sequences.

The nitro-heterocyclic compound benznidazole (BZ) is the first-line drug for the treatment of Chagas disease, caused by the protozoan Trypanosoma cruzi. However, therapeutic failures are common for reasons that include the influences of parasite and host genetics, the effects of toxicity on adherence to treatment, and difficulties in demonstrating parasitological cure. To obtain information on the origin of the resistance to BZ and eliminate from the scenery the participation of the host, initially we mapped the susceptibility to the drug in thirteen species of seven genera of the family Trypanosomatidae.

Investigating the structure-activity relationships of N'-[(5-nitrofuran-2-yl) methylene] substituted hydrazides against Trypanosoma cruzi to design novel active compounds.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected chronic tropical infection endemic in Latin America. New and effective treatments are urgently needed because the two available drugs - benznidazole (BZD) and nifurtimox (NFX) - have limited curative power in the chronic phase of the disease. We have previously reported the design and synthesis of N'-[(5-nitrofuran-2-yl) methylene] substituted hydrazides that showed high trypanocidal activity against axenic epimastigote forms of three T.

[Low back pain during pregnancy].

Objective: Low back pain is a common complaint among pregnant women. It is estimated that about 50% of pregnant women complain of some form of back pain at some point in pregnancy or during the postpartum period. The aim of this study was to evaluate the frequency of low back pain during pregnancy and its characteristics.

[Anesthesiologists' knowledge about packed red blood cells transfusion in surgical patients].

Introduction: Blood is an important resource in several lifesaving interventions, such as anemia correction and improvement of oxygen transport capacity. Despite advances, packed red blood cell (PRBC) transfusion still involves risks. The aim of this study was to describe the knowledge of anesthesiologists about the indications, adverse effects, and alternatives to red blood cell transfusion intraoperatively.

"True" posterior communicating aneurysms: Three cases, three strategies.

Background: The authors provide a review of true aneurysms of the posterior communicating artery (PCoA). Three cases admitted in our hospital are presented and discussed as follows.

Case Descriptions: First patient is a 51-year-old female presenting with a Fisher II, Hunt-Hess III (headache and confusion) subarachnoid hemorrhage (SAH) from a ruptured true aneurysm of the right PCoA.

A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole.

Benznidazole (BZ) is one of the two drugs used for Chagas disease treatment. Nevertheless therapeutic failures of BZ have been reported, which were mostly attributed to variable drug susceptibility among Trypanosoma cruzi strains. ATP-binding cassette (ABC) transporters are involved in a variety of translocation processes and some members have been implicated in drug resistance.

Designing and exploring active N'-[(5-nitrofuran-2-yl) methylene] substituted hydrazides against three Trypanosoma cruzi strains more prevalent in Chagas disease patients.

Chagas disease affects around 8 million people worldwide and its treatment depends on only two nitroheterocyclic drugs, benznidazole (BZD) and nifurtimox (NFX). Both drugs have limited curative power in chronic phase of disease. Nifuroxazide (NF), a nitroheterocyclic drug, was used as lead to design a set of twenty one compounds in order to improve the anti-Trypanosoma cruzi activity.

Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease.

Therapeutic failure of benznidazole (BZ) is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years.

Multiple cervical arcocristectomies for the treatment of cervical spondylotic myelopathy: surgical technique and results.

Object: In the surgical treatment of cervical spondylotic myelopathy, a posterior approach is recommended for patients with multilevel cervical stenosis. In this article the authors describe the multiple cervical arcocristectomy technique and results.

Methods: This surgical technique involves the removal of the upper half of the cervical laminae and was performed in 17 patients between 1997 and 2005 with a mean follow-up of 55 months.

Differential transcription profiles in Trypanosoma cruzi associated with clinical forms of Chagas disease: Maxicircle NADH dehydrogenase subunit 7 gene truncation in asymptomatic patient isolates.

The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form). Every year 2-3% of these individuals develop severe clinical manifestations (cardiac and digestive forms). In this study a Trypanosoma cruzi DNA microarray was used to compare the transcript profiles of six human isolates: three from asymptomatic and three from cardiac patients.