Publications (62) View all
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Article: Chronic Chagas disease: from basics to laboratory medicine.
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ABSTRACT: Abstract Chagas disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America and has huge potential to become a worldwide problem, due to increasing migration, and international tourism, as well as infectant transfer by blood contact and transfusion, intrauterine transfer, and organ transplantation. Nearly 30% of chronically-infected patients become symptomatic, often with a latency of 10-30 years, developing life-threatening complications. Of those, nearly 90% develop Chagas heart disease, while the others manifest gastrointestinal disease and neuronal disorders. Besides interrupting the infection cycle and chemotherapeutic infectant elimination, starting therapy early in symptomatic patients is important for counteracting the disease. This would be essentially supported by optimized patient management, involving risk assessment, early diagnosis and monitoring of the disease and its treatment. From economic and logistic viewpoints, the tools of laboratory medicine should be especially able to guarantee this. After summarizing the basics of chronic Chagas disease, such as the epidemiological data, the pathogenetic mechanisms thought to drive symptomatic Chagas disease and also treatment options, we present tools of laboratory medicine that address patient diagnosis, risk assessment for becoming symptomatic and guidance, focusing on autoantibody estimation for risk assessment and heart marker measurement for patient guidance. In addition, increases in levels of inflammation and oxidative stress markers in chronic Chagas disease are discussed.Clinical Chemistry and Laboratory Medicine 10/2012; · 2.15 Impact Factor -
Article: Chronic Chagas' heart disease–From pathogenesis to treatment regimes
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ABSTRACT: Chagas' disease, caused by Trypanosoma cruzi infection, was discovered nearly 100 years ago (1909) by the Brazilian physician Carlos Chagas. Chronic Chagas' disease is still ranked as the most serious parasitic disease in Latin America. Infected patients remain lifelong parasite carri-ers. With a latency of 10 to 30 years, nearly one third of parasite carriers develop life-threaten-ing complications: the majority develop Chagas' heart disease (90%). Gastrointestinal disor-ders (megaesophagus, megacolon) and neuronal afflictions mainly affecting the parasympa-thetic nerve system were found in the others. Chagas' heart disease presenting with sudden death, heart failure, malign cardiac arrhythmia, and thromboembolism is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and employment situations. Chagas' disease is start-ing to become a worldwide problem due to migration, international tourism and parasite trans-fer by blood contact, intrauterine transfer and organ transplantation. In this review, we reflect on the epidemiology and etiopathology of Chagas' heart disease. We summarize the mecha-nisms that have been suggested to drive Chagas' heart disease, mainly those based on autoim-munity phenomena. In this context, we focus on autoantibodies directed to G-protein coupled receptors. Following the autoimmunity story in chronic Chagas' heart disease – and in addi-tion to antiparasitic therapy, the treatment of heart failure, arrhythmia and thromboembolism and under study strategies such as heart transplantation and cell therapy – we describe regimes that use peptides and aptamers for autoantibody removal or neutralization. At present, such regimes are mostly proposed for beta-1-receptor autoantibodies in patients with dilated car-diomyopathy but, in principle, they can be adapted for patients with chronic Chagas' heart dis-ease who are positive for comparable autoantibodies.Applied cardiopulmonary pathophysiology: ACP 01/2012; 16:55-81. -
Article: Aptamer neutralization of beta1-adrenoceptor autoantibodies isolated from patients with cardiomyopathies.
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ABSTRACT: Autoantibodies directed against the beta1-adrenoceptor (beta1-AABs) have been proposed to drive the pathogenesis of idiopathic dilated cardiomyoparthy (DCM), Chagas' cardiomyopathy, and peripartum cardiomyopathy. For disease treatment, aptamers that bind and neutralize beta1-AABs could be significant. We determined whether oligonucleotide-aptamers, selected to target human beta1-AABs directed against the second extracellular loop of the beta1-AAB, can neutralize these AABs and modulate their function in vitro. Using Monolex technology, we identified an ssDNA aptamer that targets human beta1-AABs. The neutralization potential of this aptamer against beta1-AABs isolated from patients with DCM, Chagas' cardiomyopathy, and peripartum cardiomyopathy was analyzed using cultured neonatal rat cardiomyocytes by monitoring beta1-AAB induced cell toxicity and chronotropic cell responses. Aptamer addition reduced beta1-AAB induced cell toxicity and neutralized chonotropic beta1-AAB function in a dose-dependent manner. In the presence of aptamer neutralized beta1-AABs, cells remained fully responsive to agonists and antagonists, such as isoprenaline and bisoprolol. Both aptamer pretreated with a complementary (antisense) aptamer and a control scrambled-sequence aptamer were ineffective at beta1-AAB neutralization. Beta1-AABs directed against the first extracellular loop of the beta1-receptor and AABs directed against other G-protein coupled receptors were not affected by the selected aptamer. A specific aptamer that can neutralize cardiomyopathy associated human beta1-AABs in vitro has been identified and characterized, providing a framework for future in vivo testing of this treatment option in animal experiments.Circulation Research 08/2011; 109(9):986-92. · 9.49 Impact Factor -
Article: Cardiac troponin T measured with a highly sensitive assay for diagnosis and monitoring of heart injury in chronic Chagas disease.
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ABSTRACT: Chronic Chagas disease (15 million patients; annual incidence, 40, 000 patients; annual mortality, 12 ,500 patients) is the most serious parasitic disease in Latin America. Between 10 and 30 years after infection, 30% of patients with Chagas disease develop heart injury, which is the main reason for its high mortality. Consequently, frequent cardiac diagnostics are required for patients with Chagas disease. To minimize time-intensive and cost-intensive diagnostics, such as electrocardiography, echocardiography, and radiologic imaging, we tested the effect of measuring serum cardiac troponin T (cTnT) with a highly sensitive assay. To indicate the pathophysiologic background for cTnT release in Chagas heart injury, inflammation markers, such as C-reactive protein and interleukin 6, were measured in parallel. Serum cTnT was measured in 26 healthy subjects and in 179 patients with chronic Chagas disease who were asymptomatic (indeterminate stage, n = 86), who were suffering from cardiomyopathy with or without megacolon (n = 71), or who were suffering from megacolon exclusively (n = 22). Serum cTnT was significantly higher in patients with cardiomyopathy with or without megacolon than in healthy subjects, asymptomatic subjects, and patients with megacolon, and the cTnT value was correlated with the severity of the cardiomyopathy. The lower limit of detection for the highly sensitive assay (3 ng/L) was best at distinguishing patients with, and without, heart injury. C-reactive protein and interleukin 6 were found to parallel cTnT changes in both the different Chagas groups and the cardiomyopathy groups separated by disease severity. Highly sensitive cTnT measurement has the potential to contribute to diagnosis and monitoring of heart injury in patients with chronic Chagas disease. The highly sensitive assay of cTnT release seems to be related to Chagas heart disease-specific inflammation.Archives of pathology & laboratory medicine 02/2011; 135(2):243-8. · 2.58 Impact Factor -
Article: Chronic Chagas' heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine.
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ABSTRACT: Chagas' disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America. Nearly 30% of infected patients develop life-threatening complications, and with a latency of 10-30 years, mostly Chagas' heart disease which is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and labor situations. Because of increasing migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation, Chagas' heart disease could potentially become a worldwide problem. To raise awareness of this problem, we reflect on the epidemiology and etiopathology of Chagas' disease, particularly Chagas' heart disease. To counteract Chagas' heart disease, in addition to the general interruption of the infection cycle and chemotherapeutic elimination of the infection agent, early and effective causal or symptomatic therapies would be indispensable. Prerequisites for this are improved knowledge of the pathogenesis and optimized patient management. From economic and logistics viewpoints, this last prerequisite should be performed using laboratory medicine tools. Consequently, we first summarize the mechanisms that have been suggested as driving Chagas' heart disease, mainly those associated with the presence of autoantibodies against G-protein-coupled receptors; secondly, we indicate new treatment strategies involving autoantibody apheresis and in vivo autoantibody neutralization; thirdly, we present laboratory medicine tools such as autoantibody estimation and heart marker measurement, proposed for diagnosis, risk assessment and patient guidance and lastly, we critically reflect upon the increase in inflammation and oxidative stress markers in Chagas' heart disease.Heart Failure Reviews 12/2010; 17(1):45-64. · 3.20 Impact Factor
