Association between altered tryptophan metabolism, plasma aryl hydrocarbon receptor agonists, and inflammatory Chagas disease.

Introduction: Chagas disease causes a cardiac illness characterized by immunoinflammatory reactions leading to myocardial fibrosis and remodeling. The development of Chronic Chagas Cardiomyopathy (CCC) in some patients while others remain asymptomatic is not fully understood, but dysregulated inflammatory responses are implicated. The Aryl hydrocarbon receptor (AhR) plays a crucial role in regulating inflammation.

Discovery of circulating miRNAs as biomarkers of chronic Chagas heart disease via a small RNA-Seq approach.

Chagas disease affects approximately 7 million people worldwide in Latin America and is a neglected tropical disease. Twenty to thirty percent of chronically infected patients develop chronic Chagas cardiomyopathy decades after acute infection. Identifying biomarkers of Chagas disease progression is necessary to develop better therapeutic and preventive strategies.

Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression.

infection in humans leads to progression to chronic chagasic myocarditis (CCM) in 30% of infected individuals, paralleling T cell inflammatory infiltrates in the heart tissue. T-cell trafficking into the hearts of CCM patients may be modulated by expression of chemotactic or haptotactic molecules, as the chemokine CXCL12, the cytokine tumor necrosis factor-alpha (TNF-α), and extracellular matrix proteins (ECM), such as fibronectin. Herein we evaluated the expression of fibronectin, CXCL12, and TNF-α in the myocardial tissue of seropositive (asymptomatic or with CCM), as well as seronegative individuals as healthy controls.

Diminished Prolinemia in Chronic Chagasic Patients: A New Clue for Disease Pathology?

, the etiological agent of Chagas disease, is dependent on proline for a variety of processes, such as energy metabolism, host cell invasion, differentiation, and resistance to osmotic, metabolic, and oxidative stress. On this basis, we investigated a possible relationship between prolinemia and severity of infection in chronic patients, as reported here. The study population consisted of 112 subjects, separated into 83 chronically -infected patients and 29 age-matched healthy volunteers (control) of both sexes, recruited at the Chagas Disease Service from the Department of Cardiology, Hospital Provincial del Centenario de Rosario (Rosario, Argentina).

Dysregulated Network of Immune, Endocrine and Metabolic Markers is Associated to More Severe Human Chronic Chagas Cardiomyopathy.

Individuals who are infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC), which is a complication involving a series of immune pathogenetic mechanisms, although an association between immune and metabolic alterations was more recently proposed. Accordingly, we investigated the immuno-metabolic response in chagasic patients and their possible influence on CCC pathogenesis. To this end, T.

Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial.

Background: Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers.

Objectives: The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T.

Dietary intake and nutritional status of patients with Chagas disease.

Chagas disease is a parasitic infection that affects 17 million people in Latin America. The real influence of nutritional status and food intake effect over the course of the disease to chronic Chagas Cardiomyopathy is still unknown. Furthermore, some cardiovascular risk factors might influence the evolution of the disease.

Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.

The protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive.

Assessment of cross-reactive host-pathogen antibodies in patients with different stages of chronic Chagas disease.

Introduction And Objectives: Trypanosoma cruzi infection has been shown to induce humoral autoimmune responses against host antigens tissues. Particularly, antibodies cross-reacting with myocardial antigens may play a role in the development of the severe forms of chronic Chagas disease. The aim of this study was to determine the association between clinical stage of the disease and the presence of autoantibodies in patients with chronic Chagasic disease.

Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease.

Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery.

Distribution of HLA-DRB1 alleles in Argentinean patients with Chagas' disease cardiomyopathy.

Chronic Chagas' disease occurs in a variable number of infected individuals and mainly manifests as an inflammatory cardiomyopathy that may lead to a fatal course. The factors underlying the establishment of chronic myocardial lesions are not fully understood. The study included 71 unrelated individuals serologically positive for T.

Cardiovascular risk factors in chronic Chagas' disease are associated with a different profile of putative heart-pathogenic antibodies.

Given that cardiovascular risk factors (CRF), such as smoking, alcoholism and hypertension, may contribute to the development of heart lesions, chronically Trypanosoma cruzi-infected individuals were studied to explore the relationship between the presence of such CRF, cardiomyopathy and antibodies that have been proposed to play a pathogenetic role in Chagas' disease. The targets of these antibodies were T. cruzi antigens such as cruzipain (Cz), a P ribosomal antigen (P2), and a component of myelin sheaths also present in T.

HLA class II DRB1 polymorphism in Argentinians undergoing chronic Trypanosoma cruzi infection.

DNA typing of human lymphocyte antigen (HLA)-dicloro-1-[beta]-D-ribofuranosyl-benzimidazole 1 (DRB1) alleles in 35 individuals serologically positive for T. cruzi and in 41 healthy controls was performed. DRB1*0409 allele was significantly more prevalent in seropositive individuals, with a trend being also observed for the DRB1*0701 and DRB1*1503 alleles.

Adrenergic nervous system influences on the induction of ventricular tachycardia.

Background: Sudden cardiac death is a major cause of mortality in western countries and the ventricular tachyarrhythmias are mainly involved in this regard. The adrenergic autonomic nervous system has influences in provoking life-threatening arrhythmias, and the prevention of such arrhythmias with beta-blockers supports this viewpoint. To evaluate the effect of the adrenergic nervous system and some catecholamine-releasing stimuli on the induction of ventricular tachycardia, we decided to explore the occurrence of ventricular tachycardia in patients subjected to three consecutive tests, exercise testing, isoproterenol infusion, and mental stress.