scholarly journals Physical Exercise Promotes a Reduction in Cardiac Fibrosis in the Chronic Indeterminate Form of Experimental Chagas Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yasmin Pedra-Rezende ◽  
Juliana M. C. Barbosa ◽  
Ana Cristina S. Bombaça ◽  
Luiza Dantas-Pereira ◽  
Daniel Gibaldi ◽  
...  

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease and a health problem in Latin America. Etiological treatment has limited effectiveness in chronic CD; thus, new therapeutic strategies are required. The practice of physical exercises has been widely advocated to improve the quality of life of CD patients. The most frequent clinical CD manifestation is the chronic indeterminate form (CIF), and the effect of physical exercises on disease progression remains unknown. Here, in a CIF model, we aimed to evaluate the effect of physical exercises on cardiac histological, parasitological, mitochondrial, and oxidative metabolism, electro and echocardiographic profiles, and immunological features. To establish a CIF model, BALB/c and C57BL/6 mice were infected with 100 and 500 trypomastigotes of the Y T. cruzi strain. At 120 days postinfection (dpi), all mouse groups showed normal PR and corrected QT intervals and QRS complexes. Compared to BALB/c mice, C57BL/6 mice showed a lower parasitemia peak, mortality rate, and less intense myocarditis. Thus, C57BL/6 mice infected with 500 parasites were used for subsequent analyses. At 120 dpi, a decrease in cardiac mitochondrial oxygen consumption and an increase in reactive oxygen species (ROS) were detected. When we increased the number of analyzed mice, a reduced heart rate and slightly prolonged corrected QT intervals were detected, at 120 and 150 dpi, which were then normalized at 180 dpi, thus characterizing the CIF. Y-infected mice were subjected to an exercise program on a treadmill for 4 weeks (from 150 to 180 dpi), five times per week in a 30–60-min daily training session. At 180 dpi, no alterations were detected in cardiac mitochondrial and oxidative metabolism, which were not affected by physical exercises, although ROS production increased. At 120 and 180 dpi, comparing infected and non-infected mice, no differences were observed in the levels of plasma cytokines, indicating that a crucial biomarker of the systemic inflammatory profile was absent and not affected by exercise. Compared with sedentary mice, trained Y-infected mice showed similar parasite loads and inflammatory cells but reduced cardiac fibrosis. Therefore, our data show that physical exercises promote beneficial changes that may prevent CD progression.

2019 ◽  
Vol 20 (16) ◽  
pp. 4064 ◽  
Author(s):  
Carolina Kymie Vasques Nonaka ◽  
Carolina Thé Macêdo ◽  
Bruno Raphael Ribeiro Cavalcante ◽  
Adriano Costa de Alcântara ◽  
Daniela Nascimento Silva ◽  
...  

Chagas disease (CD) affects approximately 6–7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dunia Margarita Medina-Buelvas ◽  
Elizabet Estrada-Muñiz ◽  
Miriam Rodríguez-Sosa ◽  
Mineko Shibayama ◽  
Libia Vega

AbstractSome reports suggest that exposure to organophosphorus (OP) pesticides increases the incidence of infections. Ethylated dialkylphosphates (EtDAPs) are metabolites of OP pesticides widely distributed with immunomodulatory potential. Chagas disease is produced by Trypanosoma cruzi parasites, and resolution of this infection requires the activation of inflammatory macrophages (MΦ), which results in cardiac fibrosis. Some reports indicate that EtDAPs increase the amount of the anti-inflammatory alternatively activated MΦ (M2; CD206+F4/80+). Therefore, we analyzed the course of T. cruzi infection, MΦ profiles from peritoneal exudate cells (PECs), inflammatory cell infiltration and fibrosis in the heart of BALB/c mice exposed to diethyldithiophosphate (DEDTP), diethylthiophosphate (DETP) or diethylphosphate (DEP, 0.01 g/kg), common DAPs produced by OP pesticides, 24 h before infection with T. cruzi. We found that DEDTP increased the parasite burden in blood by 99% at the peak of the infection and enhanced the myocardial damage due to an increase in infiltrated inflammatory cells (induced by DEDTP or DETP) and fibrosis (induced by EtDAPs). In the PECs, exposure to EtDAPs increased the proportion of the MΦ subpopulations of M2a, M2b and M2d, which are associated with tissue repair. These results indicate that exposure to EtDAPs can exacerbate the acute phase of a parasitic infection and increase the long-term damage to the heart.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kang Sun ◽  
Yi-yuan Li ◽  
Jin Jin

AbstractThe response of immune cells in cardiac injury is divided into three continuous phases: inflammation, proliferation and maturation. The kinetics of the inflammatory and proliferation phases directly influence the tissue repair. In cardiac homeostasis, cardiac tissue resident macrophages (cTMs) phagocytose bacteria and apoptotic cells. Meanwhile, NK cells prevent the maturation and transport of inflammatory cells. After cardiac injury, cTMs phagocytose the dead cardiomyocytes (CMs), regulate the proliferation and angiogenesis of cardiac progenitor cells. NK cells prevent the cardiac fibrosis, and promote vascularization and angiogenesis. Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage. Reversely, type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage. Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines, and then release anti-inflammatory cytokines and growth factors, which regulate cardiac remodeling. In this process, dendritic cells (DCs) mediate the regulation of monocyte and macrophage recruitment. Recruited eosinophils and Mast cells (MCs) release some mediators which contribute to coronary vasoconstriction, leukocyte recruitment, formation of new blood vessels, scar formation. In adaptive immunity, effector T cells, especially Th17 cells, lead to the pathogenesis of cardiac fibrosis, including the distal fibrosis and scar formation. CMs protectors, Treg cells, inhibit reduce the inflammatory response, then directly trigger the regeneration of local progenitor cell via IL-10. B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.


2013 ◽  
Vol 32 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Marcus Vinicius Amaral da Silva Souza ◽  
Carla Cristiane Santos Soares ◽  
Juliana Rega de Oliveira ◽  
Cláudia Rosa de Oliveira ◽  
Paloma Hargreaves Fialho ◽  
...  

2017 ◽  
Vol 2 (4) ◽  
pp. 172-177
Author(s):  
Saeid Tanoorsaz ◽  
Naser Behpoor ◽  
Vahid Tadibi

Introduction: Cardiac apoptosis is one of the most important cardiovascular complications of diabetes. We aimed to investigate the changes of caspase-8, Bcl-2, and N-terminal pro B-type natriuretic peptide (NT-proBNP) in cardiac tissue after 4 weeks of aerobic exercise in male rats with diabetes. Methods: Forty adult male rats were randomly allocated to healthy control, diabetes, control + exercise and exercise + diabetes groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) solution (55 mg/kg). Two weeks after injection, fasting blood glucose levels were measured. After the induction of diabetes, the exercise program was performed for 4 weeks (5 sessions per week) at a speed of 15 to 18 m/min for 25 to 44 minutes. Forty-eight hours after the last training session, the subjects were anesthetized and the heart muscle was removed. Caspase-8, Bcl-2 and NT-proBNP levels were measured by ELISA method. Results: The induction of diabetes in the control group resulted in a significant increase in caspase-8, and NT-proBNP levels while an insignificant increase was observed for Bcl-2 levels (P<0.05). In non-diabetic groups, exercise caused no changes in caspase-8, NT-proBNP and Bcl-2 (P<0.05). Exercise in diabetic groups significantly decreased NT-proBNP while no changes were observed in caspase-8 and Bcl-2 (P<0.05). Conclusion: Our findings showed that diabetes increases the pro-apoptotic and anti-apoptotic agent. In addition, 4 weeks of regular aerobic exercises can be used as a non-pharmacological strategy to reduce the complications of apoptosis in diabetic cardiomyocytes.


Author(s):  
Auksė Arbačiauskaitė ◽  
Vilma Dudonienė

Background. Juvenile idiopathic arthritis (JIA) is the most common and most diffcult chronic rheumatic disease in children. Exercise helps to avoid joint deformities or corrects them, also reduces pain and disease activity, normalizes physical function, growth and development, improves the patient’s quality of life. So far, there is no consensus on what kind of exercise is appropriate for children with juvenile idiopathic arthritis. Goal of the research. To defne the most often applied physiotherapy techniques and their impact on the treatment of children and adolescents with juvenile idiopathic arthritis analysing and summarizing scientifc articles. Methods. Twelve articles have been analysed. Systemic literature overview involved the articles on clinical research which were selected in the light of the following criteria: children with juvenile’s idiopathic arthritis; classic clinical tests performed; application of different physical exercises and survey of their accessibility; Childhood Health Assessment questionnaire; language and year of publication (2000–2015). Results. Research participants in the selected articles were 525 research children and adolescents with juvenile idiopathic arthritis. Their mean age ± SD was 11.2 ± 2.9 years (range 4–21 years). There were 348 (66%) girls and 177 (34%) boys. Aquatic therapy and Pilates workout had the strongest effect on pain relief, general physical performance and life quality, whereas balance and proprioception exercises had the best effect on balance and mobility. The results showed that regular physical exercises did not increase pain, they reduced the number of swollen joints, they were safe and effcient, also, that high-intensity aerobic exercises did not provide additional benefts, so it may suggest that low-intensity exercise program is more suitable for children with JIA because it is a slow and mild. Conclusion. Analysis of 12 articles have shown that general physical exercises (33.5%) and aquatic therapy (33.5%) are used most often, whereas balance-proprioception exercises are less frequent (17%), Pilates workout (8%) and Qigong relaxation (8%) are used very rarely. The most effcient methods for the improvement of general physical performance, quality of life, and reducing pain include aquatic therapy, Pilates workout and Qigong therapy. Balance-proprioception exercises are proved to be most effective in the improvement of mobility and balance.Keywords: juvenile idiopathic arthritis, physical exercises, training, physiotherapy, physical condition, life quality.


2018 ◽  
Vol 51 (6) ◽  
pp. 827-830
Author(s):  
Glauco Andre Machado ◽  
Dalton Alexandre dos Anjos ◽  
Flávia de Freitas Rodrigues ◽  
Renata Fockink dos Anjos ◽  
Marcelo Barbosa Melo Luckemeyer ◽  
...  

2013 ◽  
Vol 41 (2) ◽  
pp. 687-693 ◽  
Author(s):  
Madhumita Dandapani ◽  
D. Grahame Hardie

AMPK (AMP-activated protein kinase) is a sensor of cellular energy status that appears to have arisen during early eukaryotic evolution. In the unicellular eukaryote Saccharomyces cerevisiae, the AMPK orthologue is activated by glucose starvation and is required for the switch from glycolysis (fermentation) to oxidative metabolism when glucose runs low. In mammals, rapidly proliferating cells (including tumour cells) and immune cells involved in inflammation both tend to utilize rapid glucose uptake and glycolysis (termed the Warburg effect or aerobic glycolysis) rather than oxidative metabolism to satisfy their high demand for ATP. Since mammalian AMPK, similar to its yeast orthologue, tends to promote the more energy-efficient oxidative metabolism at the expense of glycolysis, it might be expected that drugs that activate AMPK would inhibit cell proliferation and and hence cancer, as well as exerting anti-inflammatory effects. Evidence supporting this view is discussed, including our findings that AMPK is activated by the classic anti-inflammatory drug salicylate.


2008 ◽  
Vol 41 (3) ◽  
pp. 315-319 ◽  

Trypanosoma cruzi infection is often not detected early on or actively diagnosed, partly because most infected individuals are either asymptomatic or oligosymptomatic. Moreover, in most places, neither blood banks nor healthcare units offer diagnostic confirmation or treatment access. By the time patients present clinical manifestations of advanced chronic Chagas disease, specific treatment with current drugs usually has limited effectiveness. Better-quality serological assays are urgently needed, especially rapid diagnostic tests for diagnosis patients in both acute and chronic phases, as well as for confirming that a parasitological cure has been achieved. Some new antigen combinations look promising and it is important to assess which ones are potentially the best, together with their requirements in terms of investigation and development. In August 2007, a group of specialized researchers and healthcare professionals met to discuss the state of Chagas infection diagnosis and to build a consensus for a plan of action to develop efficient, affordable, accessible and easy-to-use diagnostic tests for Chagas disease. This technical report presents the conclusions from that meeting.


2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Mauricio Llaguno ◽  
Marcos Vinicius da Silva ◽  
Lara Rocha Batista ◽  
Djalma Alexandre Alves da Silva ◽  
Rodrigo Cunha de Sousa ◽  
...  

ABSTRACT The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet+ IFN-γ+) and a significantly higher IFN-γ+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25− and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4+ T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.


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