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1.
Rev Soc Bras Med Trop ; 52: e20190386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800924

RESUMO

INTRODUCTION: Chronic chagasic cardiopathy (CCC) is essentially a dilated cardiomyopathy in which a subacute, but constant chronic inflammatory process causes progressive destruction of the heart tissue. The action of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and anti-inflammatory cytokines, like interleukin IL-10 and IL-17, plays a fundamental role in the immunopathogenesis and evolution of disease. Early anti-congestive therapy, aimed at changing the morbidity and mortality rate, has been shown to reduce disease progression and to alter patients' immune response pattern. METHODS: This cross-sectional study aimed to evaluate the profile of Th1 and Th17 cytokines and IL-17, TNF-α, and IFN-γ expressions in different stages of CCC. Forty patients affected by chronic Chagas disease were divided into different groups according to the stage of the pathology. In agreement with the Brazilian consensus on Chagas disease, patients were classified as presenting an undetermined form, a cardiac form and a digestive form. Serum IFN-γ, TNF-α, IL-10, and IL-17 were evaluated. RESULTS: Lower serum IFN-γ concentrations were detected in patients receiving angiotensin-converting enzyme inhibitors (p = 0.0182), but not in those using angiotensin receptor blockers (p = 0.0783). Patients using amiodarone and aldosterone antagonist presented higher serum TNF-α concentrations (p = 0.0106 and 0.0187, respectively). IL-10 and IL-17 levels did not differ between the study groups (p = 0.7273 and p = 0.6697, respectively). CONCLUSIONS: These results suggest that the cytokine profile and disease progression are altered by anti-congestive medications commonly prescribed for CCC.


Assuntos
Cardiomiopatia Chagásica/imunologia , Citocinas/sangue , Adulto , Idoso , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/tratamento farmacológico , Doença Crônica , Estudos Transversais , Citocinas/imunologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Can J Physiol Pharmacol ; 97(2): 140-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557036

RESUMO

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 µU/mL) when compared with control (8.0 ± 4.9 µU/mL) and IDC (9.9 ± 5.0 µU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 µg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.


Assuntos
Adipocinas/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Chagásica/metabolismo , Insulina/sangue , Adipocinas/metabolismo , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Coração , Frequência Cardíaca/fisiologia , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
3.
J Electrocardiol ; 51(6): 1039-1043, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30497727

RESUMO

Chagas cardiomyopathy is the most harmful complication of Chagas disease. The electrocardiogram is a well-studied exam and has been considered an important tool for detection and evaluation of Chagas cardiomyopathy since the first years of its description. Many of its abnormalities have been described as associated with a worse prognosis. Serum BNP levels were described as inversely related to the left ventricular ejection fraction and as an independent predictor of death. It was not reported how electrocardiographic alterations correlate to NT-proBNP and its analog. The present study aims to describe the baseline electrocardiograms of a large cohort of patients with Chagas disease from endemic area and to establish an association between the number of electrocardiogram alterations and high levels of NT-ProBNP in Chagas disease patients. This study selected 1959 Chagas disease patients in 21 municipalities within a limited region in the northern part of the State of Minas Gerais (Brazil), 1084 of them had Chagas cardiomyopathy. NT-proBNP levels were suggestive of heart failure in 11.7% of this population. One or more electrocardiographic alterations have an Odds Ratio of 9.12 (CI 95% 5.62-14.80) to have NT-proBNP elevation. Considering the association between the number of 1, 2, and 3 or more alterations in electrocardiogram and NT-proBNP elevation, the ORs were 7.11 (CI 95% 4.33-11.67); 16.04 (CI 95% 9.27-27.77) and 47.82 (CI 95% 17.98-127.20), respectively. The presence and the number of typical electrocardiographic alterations of Chagas disease are independently associated with the severity of the cardiomyopathy.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Eletrocardiografia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Biomarcadores/sangue , Brasil , Cardiomiopatia Chagásica/sangue , Doença de Chagas/epidemiologia , Estudos de Coortes , Estudos Transversais , Doenças Endêmicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
4.
Rev Inst Med Trop Sao Paulo ; 60: e57, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30365640

RESUMO

The vasoactive intestinal peptide (VIP) expression is lower in cardiac chagasic patients and is related to worse cardiac function. The reduction of VIP in patients with Chagas disease may be a result of its enhanced degradation. To test this hypothesis, the tryptase and chymase expression was evaluated. We also related VIP levels with interleukin-17 (IL-17) expression since VIP may modulate IL-17 production. Plasma levels of chymase were higher in chagasic patients. Conversely, VIP/chymase and VIP/tryptase ratios were lower in chagasic patients when compared to non-infected individuals. Besides, the VIP/chymase ratio was lower in chagasic cardiac patients in comparison with the indeterminate group. A positive correlation between tryptase and chymase levels was observed in chagasic cardiac patients. In relation to IL-17, we observed a higher expression of this cytokine in the cardiac form of the disease than in the indeterminate form. IL-17/VIP ratio was higher in the cardiac form in comparison with non-infected or indeterminate form. These results suggest that the low levels of VIP observed in chagasic patients could be due to an increased production of chymase and/or to the additive effect of the interaction between chymase and tryptase in the cardiac form. Moreover, the decreased VIP expression may contribute to the increase of IL-17 in chagasic cardiac patients.


Assuntos
Cardiomiopatia Chagásica/metabolismo , Interleucina-17/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Cardiomiopatia Chagásica/sangue , Quimases/sangue , Estudos Transversais , Humanos , Triptases/sangue , Peptídeo Intestinal Vasoativo/sangue
5.
Mem Inst Oswaldo Cruz ; 113(10): e180224, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30133549

RESUMO

BACKGROUND: Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients with Chagas cardiomyopathy (ChC) than in patients with non-dilated chagasic cardiomyopathy. However, its prognostic value was not established in patients with ChC. METHODS: Forty-nine patients with ChC (50 ± 7 years, New York Heart Association "NYHA" I-III); were evaluated by echocardiography, exercise testing, and blood analysis. Serum BDNF levels were determined using enzyme-linked immunosorbent assay sandwich. Patients were followed-up, and cardiac death was considered the end-point. The survival analyses were performed using Kaplan-Meier and Cox regression. RESULTS: After 39 ± 14 months of follow-up, 12 patients (25%) died. The concentration of 2.5 ng/mL was the optimal cut-off value to predict survival with significant difference between the groups with low (≤ 2.5 ng/mL) and high (> 2.5 ng/mL) BDNF levels (p = 0.006). Lower serum BDNF levels (hazards ratio (HR) 1.1, 95% confidence interval (CI) 1.1-1.4; p = 0.001), peak oxygen uptake (HR 1.2, 95% CI 1.0-1.3; p = 0.009), and left ventricular ejection fraction (HR 0.8, 95% CI 0.7-0.9; p = 0.001) were the independent predictors of survival. The combination of low serum BDNF levels and reduced left ventricular ejection fraction were highly predictive of death (HR 5.6, 95% CI: 1.2-9.7; p = 0.026). CONCLUSION: In patients with ChC, reduced serum BDNF levels, especially if associated with systolic function, may provide useful prognostic information.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Cardiomiopatia Chagásica/sangue , Adulto , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia , Ensaio de Imunoadsorção Enzimática , Teste de Esforço , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Prognóstico , Estudos Prospectivos , Padrões de Referência , Medição de Risco/métodos , Fatores de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Fatores de Tempo
6.
Arq Neuropsiquiatr ; 76(1): 22-25, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29364390

RESUMO

To describe anticoagulation characteristics in patients with cardiac complications from Chagas disease and compare participants with and without cardioembolic ischemic stroke (CIS). A retrospective cohort of patients with Chagas disease, using anticoagulation, conducted from January 2011 to December 2014. Forty-two patients with Chagas disease who were using anticoagulation were studied (age 62.9±12.4 years), 59.5% female and 47.6% with previous CIS, 78.6% with non-valvular atrial fibrillation and 69.7% with dilated cardiomyopathy. Warfarin was used in 78.6% of patients and dabigatran (at different times) in 38%. In the warfarin group, those with CIS had more medical appointments per person-years of follow-up (11.7 vs 7.9), a higher proportion of international normalized ratios within the therapeutic range (57% vs 42% medical appointments, p = 0.025) and an eight times higher frequency of minor bleeding (0.64 vs 0.07 medical appointments). Patients with Chagas disease and previous CIS had better control of INR with a higher frequency of minor bleeding.


Assuntos
Anticoagulantes/uso terapêutico , Isquemia Encefálica/prevenção & controle , Cardiomiopatia Chagásica/complicações , Embolia/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Cardiomiopatia Chagásica/sangue , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Varfarina/efeitos adversos , Varfarina/uso terapêutico
7.
Mol Cell Biochem ; 438(1-2): 59-65, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28766165

RESUMO

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.


Assuntos
Acetilcolina/sangue , Acetilcolinesterase/sangue , Encéfalo/metabolismo , Cardiomiopatia Chagásica/sangue , Linfócitos/metabolismo , Trypanosoma cruzi , Animais , Encéfalo/patologia , Cardiomiopatia Chagásica/patologia , Linfócitos/patologia , Camundongos , Óxido Nítrico/sangue , Peroxidase/sangue
8.
Front Immunol ; 9: 3015, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30662439

RESUMO

B-cells mediate humoral adaptive immune response via the production of antibodies and cytokines, and by inducing T-cell activation. These functions can be attributed to distinct B-cell subpopulations. Infection with Trypanosoma cruzi, the causative agent of Chagas disease, induces a polyclonal B-cell activation and lytic antibody production, critical for controlling parasitemia. Individuals within the chronic phase of Chagas disease may remain in an asymptomatic form (indeterminate), or develop severe cardiomyopathy (cardiac form) that can lead to death. Currently, there is no effective vaccine to prevent Chagas disease, and no treatment to halt the development of the cardiomyopathy once it is installed. The pathology associated with cardiac Chagas disease is a result of an inflammatory reaction. Thus, discovering characteristics of the host's immune response that favor the maintenance of favorable heart function may unveil important immunotherapeutic targets. Given the importance of B cells in antibody production and parasite control, we investigated T. cruzi-derived antigenic fractions responsible for B-cell activation and whether frequencies and functional characteristics of B-cell subpopulations are associated with different clinical outcomes of human Chagas disease. We stimulated cells from indeterminate (I) and cardiac (C) Chagas patients, as well as non-infected individuals (NI), with T. cruzi-derived protein- (PRO), glycolipid- (GCL) and lipid (LIP)-enriched fractions and determined functional characteristics of B-cell subpopulations. Our results showed that the frequency of B-cells was similar amongst groups. PRO, but not GCL nor LIP, led to an increased frequency of B1 B-cells in I, but not C nor NI. Although stimulation with PRO induced higher TNF expression by B1 B-cells from C and I, as compared to NI, it induced expression of IL-10 in cells from I, but not C. Stimulation with PRO induced an increased frequency of the CD11b+ B1 B-cell subpopulation, which was associated with better cardiac function. Chagas patients displayed increased IgM production, and activation of gamma-delta T-cells, which have been associated with B1 B-cell function. Our data showed that PRO activates CD11b+ B1 B-cells, and that this activation is associated with a beneficial clinical status. These findings may have implications in designing new strategies focusing on B-cell activation to prevent Chagas disease cardiomyopathy.


Assuntos
Antígenos de Protozoários/imunologia , Linfócitos B/imunologia , Cardiomiopatia Chagásica/imunologia , Proteínas de Protozoários/imunologia , Trypanosoma cruzi/imunologia , Adulto , Idoso , Antígenos de Protozoários/metabolismo , Linfócitos B/metabolismo , Brasil , Antígeno CD11b/imunologia , Antígeno CD11b/metabolismo , Comunicação Celular/imunologia , Células Cultivadas , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/parasitologia , Estudos Transversais , Feminino , Glicolipídeos/imunologia , Glicolipídeos/metabolismo , Humanos , Imunoglobulina M/imunologia , Imunoglobulina M/metabolismo , Interleucina-10/imunologia , Interleucina-10/metabolismo , Linfócitos Intraepiteliais/imunologia , Linfócitos Intraepiteliais/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/metabolismo , Adulto Jovem
9.
Rev Soc Bras Med Trop ; 50(5): 689-692, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29160519

RESUMO

INTRODUCTION: Elucidating the molecules involved in the inflammatory process of chronic Chagas disease may allow identification of treatment targets. METHODS: The ex vivo phenotypic expression of chemokine receptors CCR1, CCR3, CCR4, CCR5, CXCR2, CXCR3, CXCR4, and CXCR5 on the CD4+ and CD8+ T-cells of patients with chronic Chagas cardiomyopathy of varying severity was evaluated using flow cytometry. RESULTS: Differential expression of CD4+CCR3+ and CD8+CCR4+ T-cells was observed in patients with mild cardiac involvement compared, respectively, with patients with severe cardiac and asymptomatic forms of Chagas disease. CONCLUSIONS: These receptors are possibly involved in the pathogenesis of chronic Chagas cardiomyopathy.


Assuntos
Linfócitos T CD4-Positivos/química , Linfócitos T CD8-Positivos/química , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/patologia , Receptores CCR/sangue , Idoso , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas
10.
Nutr J ; 16(1): 36, 2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28599665

RESUMO

BACKGROUND: Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients. METHODS: The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated. RESULTS: Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups. CONCLUSION: Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary. TRIAL REGISTRATION: NCT01863576.


Assuntos
Biomarcadores/sangue , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/tratamento farmacológico , Ácidos Graxos Ômega-3/administração & dosagem , Idoso , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Cardiomiopatias/sangue , Cardiomiopatias/tratamento farmacológico , Colesterol/sangue , Doença Crônica , Citocinas/sangue , Dieta , Suplementos Nutricionais , Método Duplo-Cego , Ácidos Graxos Ômega-3/sangue , Feminino , Seguimentos , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
11.
Int J Cardiol ; 240: 354-359, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28320606

RESUMO

BACKGROUND: Cardiac arrhythmias are one of the main causes of death in ChCP and other dilated cardiomyopathies. Previous studies demonstrated that ventricular arrhythmias are associated with the presence of autoantibodies with beta-adrenergic activity, Ab-ß. OBJECTIVES: The aim of this study was to investigate whether Ab-ß, present in chronic chagasic patients (ChCP), induce cardiac arrhythmias in the pharmacological type-2 long QT syndrome model (LQTS-2). METHODS/RESULTS: The LQTS2 was established by perfusion of Tyrode saline solution with a potassium channel blocker E-4031 (5µM) in isolated rabbit hearts or in rabbit cardiac strips, in order to record ECG or action potential, respectively. Autoantibodies from ChCP activating (Ab-ß) or not (Ab-NR) cardiac beta 1-adrenergic receptors were used. Ab-ß, but not Ab-NR, were able to significantly shorten QT, QTc and increase Tpeak-Tend interval in the LQTS-2. A positive correlation between higher QTc and Tpeak-Tend was found after Ab-ß perfusion in the same model. In addition, in the LQTS-2 model, in almost 75% (11/15) of the hearts perfused with Ab-ß, ventricular and atrio-ventricular electrical disturbances were observed. Atenolol abolished all Ab-ß-induced arrhythmias. Ab-ß, when perfused in a cellular LQTS-2, drastically reduced the action potential duration and evoked early afterdepolarization (EAD's), while Ab-NR did not modulate the AP properties in the LQTS-2. CONCLUSION: The results indicate that Ab-ß were able to induce cardiac arrhythmias and EAD's. This phenomenon can explain, at least in part, the cellular mechanism of Ab-ß-induced arrhythmias. Furthermore, atenolol is effective for the treatment of Ab-ß-induced arrhythmias.


Assuntos
Arritmias Cardíacas/sangue , Arritmias Cardíacas/fisiopatologia , Autoanticorpos/sangue , Cardiomiopatia Chagásica/sangue , Síndrome do QT Longo/fisiopatologia , Receptores Adrenérgicos beta 1/sangue , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Arritmias Cardíacas/etiologia , Eletrocardiografia/efeitos dos fármacos , Eletrocardiografia/métodos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Síndrome do QT Longo/induzido quimicamente , Estudos Longitudinais , Masculino , Coelhos , Estudos Retrospectivos
13.
Int J Cardiol ; 227: 577-582, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27839809

RESUMO

BACKGROUND/OBJECTIVES: Up 30 to 40% of Chagas patients exhibit cardiomyopathy with different degrees of cardiac involvement. Biomarkers may help in differentiation of the severity of Chagas cardiomyopathy (CCM). This study sought to examine the diagnostic value of a panel of biomarkers to distinguish the severity of (CCM). METHODS: 100 patients with CCM were included in this cross-sectional study. Based on electrocardiogram and echocardiogram, CCM patients were classified in three stages according to disease's severity. Levels of high-sensitivity cardiac troponin T (Hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), soluble ST2 (sST2) and cystatin-c (Cys-c) were measured. Logistic regression models were used to assess the association between levels of natural log-transformed values of biomarkers and stages C/D versus B. We also calculated the area under curve (AUC) for each of the models. RESULTS: In models adjusted for age, sex, body mass index, kidney function and medication use, increased levels of NT-proBNP (per 1 unit natural log-transformed values, odds ratio (OR)=5.55; 95CI%:1.65-18.72) and Hs-cTnT (per 1 unit natural log-transformed values, OR=7.11; 95CI%:1.41-35.90) showed significant association with the severity of CCM per 1 unit increase of biomarkers. The accuracy of NT-proBNP and Hs-cTnT for diagnosis of the severity of CCM was high: AUC of 0.968 and 0.956 respectively. No significant difference was found in the AUC between NT-proBNP and Hs-cTnT. No association was found between Gal-3, NGAL, sST2 and Cys-C and severity of CCM. CONCLUSIONS: NT-proBNP and Hs-cTnT have both same diagnostic value in distinguishing severity of CCM.


Assuntos
Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/mortalidade , Eletrocardiografia , Galectina 3/sangue , Peptídeo Natriurético Encefálico/sangue , Troponina T/sangue , Adulto , Fatores Etários , Idoso , Área Sob a Curva , Biomarcadores/sangue , Cardiomiopatia Chagásica/tratamento farmacológico , Cardiomiopatia Chagásica/fisiopatologia , Estudos Transversais , Cistatina C/sangue , Progressão da Doença , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Taxa de Sobrevida
14.
J Infect Dis ; 215(3): 387-395, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28003350

RESUMO

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression.


Assuntos
Cardiomiopatia Chagásica/genética , Disfunção Ventricular/genética , Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/fisiopatologia , Citotoxicidade Imunológica/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Células Matadoras Naturais/imunologia , Análise em Microsséries , Pessoa de Meia-Idade , Miocárdio/patologia , Reação em Cadeia da Polimerase em Tempo Real , Disfunção Ventricular/sangue , Disfunção Ventricular/parasitologia
15.
Trop Med Int Health ; 21(12): 1545-1551, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27699992

RESUMO

OBJECTIVE: Autoantibodies cross-reacting with the ß1 adrenergic receptor (anti-ß1AR and anti-p2ß) and cardiac myosin antigens (anti-B13) have been related to the pathogenesis of chronic Chagas heart disease (CCHD). Studies exploring their levels in different stages are scarce. We aimed to evaluate the relationship of these autoantibodies with the clinical profile of chronic patients, especially regarding their classificatory accuracy in severe presentation with heart failure. METHODS AND RESULTS: We conducted a cross-sectional study of 155 T. cruzi-seropositive patients and 26 age- and gender-matched healthy controls. They were categorised in three stages of CCHD. Serum antibodies were measured by specific immunoassays. Symptomatic individuals showed increased levels of anti-ß1AR and anti-B13, while anti-p2ß antibodies were similar between groups. A composite logistic regression model including anti-B13, anti-ß1AR antibody levels and age was able to predict systolic heart failure yielding an area under the curve of 83% (sensitivity of 67% and specificity of 89%). CONCLUSIONS: In our study, anti-ß1AR and anti-B13 antibodies were higher in individuals with chronic Chagas heart disease stage III, mainly in those with dilated cardiomyopathy associated with systolic heart failure. Logistic regression analysis showed that both antibodies were good predictors of severe CCHD. As well as being involved in disease progression, anti-ß1AR and anti-B13 antibodies may be used as a serum marker of poor prognosis in terms of heart compromise.


Assuntos
Autoanticorpos/sangue , Miosinas Cardíacas/imunologia , Cardiomiopatia Chagásica/imunologia , Insuficiência Cardíaca/etiologia , Receptores Adrenérgicos beta 1/imunologia , Trypanosoma cruzi/imunologia , Adulto , Idoso , Área Sob a Curva , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/parasitologia , Doença de Chagas , Estudos Transversais , Progressão da Doença , Feminino , Insuficiência Cardíaca/imunologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença
17.
BMJ Open ; 6(5): e011181, 2016 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-27147390

RESUMO

PURPOSE: We have established a prospective cohort of 1959 patients with chronic Chagas cardiomyopathy to evaluate if a clinical prediction rule based on ECG, brain natriuretic peptide (BNP) levels, and other biomarkers can be useful in clinical practice. This paper outlines the study and baseline characteristics of the participants. PARTICIPANTS: The study is being conducted in 21 municipalities of the northern part of Minas Gerais State in Brazil, and includes a follow-up of 2 years. The baseline evaluation included collection of sociodemographic information, social determinants of health, health-related behaviours, comorbidities, medicines in use, history of previous treatment for Chagas disease, functional class, quality of life, blood sample collection, and ECG. Patients were mostly female, aged 50-74 years, with low family income and educational level, with known Chagas disease for >10 years; 46% presented with functional class >II. Previous use of benznidazole was reported by 25.2% and permanent use of pacemaker by 6.2%. Almost half of the patients presented with high blood cholesterol and hypertension, and one-third of them had diabetes mellitus. N-terminal of the prohormone BNP (NT-ProBNP) level was >300 pg/mL in 30% of the sample. FINDINGS TO DATE: Clinical and laboratory markers predictive of severe and progressive Chagas disease were identified as high NT-ProBNP levels, as well as symptoms of advanced heart failure. These results confirm the important residual morbidity of Chagas disease in the remote areas, thus supporting political decisions that should prioritise in addition to epidemiological surveillance the medical treatment of chronic Chagas cardiomyopathy in the coming years. The São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) represents a major challenge for focused research in neglected diseases, with knowledge that can be applied in primary healthcare. FUTURE PLANS: We will continue following this patients' cohort to provide relevant information about the development and progression of Chagas disease in remotes areas, with social and economic inequalities. TRIAL REGISTRATION NUMBER: NCT02646943; Pre-results.


Assuntos
Cardiomiopatia Chagásica/epidemiologia , Doença Crônica/epidemiologia , Insuficiência Cardíaca/epidemiologia , Imunossupressores/uso terapêutico , Peptídeo Natriurético Encefálico/sangue , Nitroimidazóis/uso terapêutico , Fragmentos de Peptídeos/sangue , Idoso , Biomarcadores/sangue , Brasil/epidemiologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/tratamento farmacológico , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica/tratamento farmacológico , Progressão da Doença , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Vigilância da População , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Fatores Socioeconômicos
18.
Eur J Pharmacol ; 777: 26-32, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26927755

RESUMO

Chagas disease is caused by Trypanosoma cruzi (T. cruzi). In some patients with Chagas disease, symptoms progress to chronic chagasic cardiomyopathy. Endogenously, inflammation is resolved in the presence of lipid mediators such as aspirin-triggered RvD1 (AT-RvD1) which has anti-inflammatory and pro-resolution effects. Here, we demonstrated, for the first time, the effects of AT-RvD1 on T. cruzi antigen-stimulated peripheral blood mononuclear cells (PBMCs) from patients with Chagas heart disease. The levels of IFN-γ, TNF-α, IL-10, and IL-13 increased in PBMCs from cardiac-form Chagas patients in stage B1 (patients with fewer heart abnormalities) stimulated with T. cruzi antigen compared to those in non-stimulated PBMCs. AT-RvD1 reduced the IFN-γ concentrations in PBMCs from patients with Chagas disease stimulated with T. cruzi antigen compared to stimulated with T. cruzi antigen cells. AT-RvD1 treatment resulted in no observable changes in TNF-α, IL-10, and IL-13 levels. AT-RvD1 significantly decreased the percentage of necrotic cells and caused a significant reduction in the proliferation rate of T. cruzi antigen-stimulated PBMCs from patients with Chagas disease. These findings demonstrate that AT-RvD1 modulates the immune response in Chagas disease patients and might have potential to be used as an alternative approach for slowing the development of further heart damage.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Cardiomiopatia Chagásica/tratamento farmacológico , Cardiomiopatia Chagásica/patologia , Humanos , Interferon gama/metabolismo , Leucócitos Mononucleares/patologia , Pessoa de Meia-Idade , Necrose/patologia , Adulto Jovem
19.
Am J Trop Med Hyg ; 94(5): 1034-9, 2016 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-26976886

RESUMO

There is a significant heterogeneity in reported performance of serological assays for Chagas disease diagnosis. The conventional serology testing in laboratory diagnosis and in blood banks is unsatisfactory because of a high number of inconclusive and misclassified results. We aimed to assess the quality of four commercially available enzyme-linked immunosorbent assay tests for their ability to detect Trypanosoma cruzi antibodies in 685 sera samples. Cross-reactivity was assessed by using 748 sera from patients with unrelated diseases. Initially, we found that the reactivity index against T. cruzi antigen was statistically higher in sera from Chagas disease patients compared with those from non-chagasic patients, supporting the notion that all evaluated tests have a good discriminatory ability toward the diagnosis of T. cruzi infection in patients in the chronic phase of the disease. Although all tests were similarly sensitive for diagnosing T. cruzi infection, there were significant variations in terms of specificity and cross-reactivity among them. Indeed, we obtained divergent results when testing sera from patient with unrelated diseases, particularly leishmaniasis, with the levels of cross-reactivity being higher in tests using whole T. cruzi extracts compared with those using recombinant proteins. Our data suggest that all four tests may be used for the laboratory diagnosis and routine blood screening diagnose for Chagas disease. We also emphasize that, despite their general good performance, caution is needed when analyzing the results when these tests are performed in areas where other diseases, particularly leishmaniasis, are endemic.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Técnicas Imunoenzimáticas/métodos , Cardiomiopatia Chagásica/sangue , Doença Crônica , Humanos
20.
Rev Inst Med Trop Sao Paulo ; 57(5): 385-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26603224

RESUMO

Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease.


Assuntos
Adenosina Desaminase/sangue , Proteína C-Reativa/análise , Doença de Chagas/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Cardiomiopatia Chagásica/sangue , Doença de Chagas/enzimologia , Doença Crônica , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Espectrofotometria
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