TGF- β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas’ heart disease

by Roberto Rodrigues Ferreira, Rayane da Silva Abreu, Glaucia Vilar-Pereira, Wim Degrave, Marcelo Meuser-Batista, Nilma Val éria Caldeira Ferreira, Otacílio da Cruz Moreira, Natália Lins da Silva Gomes, Elen Mello de Souza, Isalira P. Ramos, Sabine Bailly, Jean-Jacques Feige, Joseli Lannes-Vieira, Tania C. de Araújo-Jorge, Mariana Caldas Waghabi TGF-β involvement in Chagas disease cardiomyopathy has been clearly demonstrated. The TGF-β signaling pathway is activated in the cardiac tissue of chronic phase patients and is associated with an increase in extracellular matrix protein expression. The aim of this study was to investigate the e ffect of GW788388, a selective inhibitor of TβR1/ALK5, on cardiac function in an experimental model of chronic Chagas’ heart disease. To this end, C57BL/6 mice were infected withTrypanosoma cruzi (102 parasites from the Colombian strain) and treated orally with 3mg/kg GW788388 starting at 120 days post-infection (dpi), when 100% of the infected mice show cardiac damage, and following three distinct treatment schedules: i) single dose; ii) one dose per week; or iii) three doses per week during 30 days. The treatment with GW788388 improved several cardiac parameters: reduced the prolonged PR and QTc intervals, increased heart rate, and reversed sinus arrhythmia, and atrial and atrioventricular conduction disorders. At 180 dpi, 30 days after treatment interruption, the GW3x-treated group remained ...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research

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We present a series of cases of lungworm infection in grey seals (Halichoerus grypus) associated with novel, significant and unusual pulmonary vascular changes. Grey seals (n = 180) that were stranded, in rehabilitation or in long-term captivity in the UK were subjected to post-mortem examination between 2012 and 2018. Lung tissue was collected from 47 individuals for histopathological examination. Polymerase chain reaction (PCR) on formalin-fixed and paraffin wax-embedded (FFPE) material was attempted for parasite identification on selected sections using lungworm-specific primers, and nematode morphology within...
Source: Journal of Comparative Pathology - Category: Pathology Source Type: research
Publication date: Available online 19 November 2019Source: Indian Heart JournalAuthor(s): Shamshad Alam, Sharad Chandra, Gaurav Chaudhary, Akhil Sharma, Monika Bhandhari, Pravesh Vishwakarma, Akshaya Pradhan, Rishi Sethi, Sudhanshu K. Dwivedi, Varun S. NarainAbstractBackgroundChemotherapy-induced cardiotoxicity constitutes subclinical myocardial dysfunction, arrhythmias, pericarditis, coronary vasospasm, significant symptomatic heart failure. Anthracyclines pose higher risk for long-term cardiac dysfunction, with increased incidences of morbidity and mortality. Hence, early detection of chemotherapy induced cardiac dysfunc...
Source: Indian Heart Journal - Category: Cardiology Source Type: research
Authors: Katsi V, Antoniou CK, Manolakou P, Toutouzas K, Tousoulis D Abstract Evidence suggests a crucial role for vaccines in cardiovascular disease, mediated not only by disease prevention but also by immunomodulatory effects. In the present review, it will be attempted to briefly present the effects of pathogens and vaccines on the cardiovascular system, as well as potential mechanisms for development of vaccines against cardiovascular disease per se. Current epidemiological evidence regarding vaccine effectiveness in different categories of heart disease will be discussed, as well as current international guide...
Source: Hellenic Journal of Cardiology - Category: Cardiology Tags: Hellenic J Cardiol Source Type: research
This study was performed to assess whether presence of MAC and its severity predict cardio-embolic stroke in elderly patients with first diagnosed AF.Methods: In this cross-sectional study, 72 elderly patients suffering from acute cardio-embolic stroke with first diagnosed AF and 79 elderly control group patients with first diagnosed AF and without stroke were investigated. A parasternal short-axis view at the level of the mitral annulus was used for MAC measurements. The severity of MAC was measured from the anterior to posterior edge at its greatest width.Results: MAC thicknesses were significantly higher in the stroke g...
Source: Acta Cardiologica - Category: Cardiology Tags: Acta Cardiol Source Type: research
The objective of this study was to analyze the correlation between lesions caused by Eimeria and the prevalence of coccidiosis and other alterations found in the gastrointestinal tracts of broilers produced in Brazil from 2017 to 2018. Intestinal health evaluations were performed in 32 integrations (farm) of broilers in Brazil, totaling 726 birds analyzed between the ages of 22 and 40 days. Necropsied chickens were collected at three different points, with at least three birds per shed. We analyzed the following changes in the gastrointestinal tract: presence of cellular desquamation, fluid and mucus excess, ingestion of...
Source: Parasitology International - Category: Parasitology Source Type: research
The objective of the present study was to identify risk factors leading to the development of clinical CMS, using data provided from the salmon producers. Daily production data from individual fishgroups in more than 120 salmon farms along the coast of Norway from fish put to sea in 2012-2014 was collected. The data included cause-specific mortalities, which was used to identify outbreaks of CMS and risk factors for disease.A model for describing the daily probability of outbreak of CMS in each fishgroup was developed. The model was run to find the most likely value for each of the parameters, given the observed outbreak d...
Source: Preventive Veterinary Medicine - Category: Veterinary Research Source Type: research
(Reuters Health) - With the help of some London primary school children, scientists have discovered that certain soup broths passed down from generation to generation might aid in battling malaria by interrupting the life cycle of the deadly parasite.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
CONCLUSIONS: Dex sedation during EPSs is not associated with a reduction in PSVT inducibility. The therapeutic utility of Dex during EPS arises from the predictable sedation Dex affords but is associated with an increased incidence of intraprocedure hypotension. PMID: 31743172 [PubMed - in process]
Source: Anesthesia and Analgesia - Category: Anesthesiology Authors: Tags: Anesth Analg Source Type: research
Conclusions: We suggest some distinct molecular mechanisms for production of IL-1β in innate immune cells from patients with different clinical forms of Chagas disease. MMP-2 and MMP-9 gelatinases are associated with distinct disease outcomes and IL-1β production. Introduction Chagas disease, also known as American trypanosomiasis, is a neglected parasitic disease caused by the protozoan Trypanosoma cruzi (1), that affects millions of people in the world (2). During the acute phase, a diffuse and intense inflammation in the cardiomyocytes is observed, which is composed mainly of neutrophils, monocytes, and ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractChagas disease is caused by a parasite infection endemic of the Americas. Traditionally observed in rural areas of Latin America, current migration trends have turned Chagas disease into a global epidemic. Acute infection is rarely severe and once it resolves, some patients can develop cardiomyopathy as part of the chronic form many years later. Multiple factors related with both the host and the parasite determine the susceptibility and progression to cardiomyopathy. Current imaging techniques are able to identify cardiac autonomic denervation, perfusion abnormalities, and myocardial fibrosis at an early of stage ...
Source: Journal of Nuclear Cardiology - Category: Nuclear Medicine Source Type: research
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