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1.
Rev Soc Bras Med Trop ; 53: e20190488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32638886

RESUMO

INTRODUCTION: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy. METHODS: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment. RESULTS: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04). CONCLUSIONS: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.


Assuntos
Doença de Chagas/genética , Insuficiência Cardíaca/fisiopatologia , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Adulto , Inibidores da Enzima Conversora de Angiotensina , Brasil , Estudos de Casos e Controles , Doença de Chagas/fisiopatologia , Estudos de Coortes , Progressão da Doença , Feminino , Genótipo , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade
2.
Cardiovasc Pathol ; 49: 107257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32674046

RESUMO

BACKGROUND: Chronic Chagas disease (CCHD) associated with Systemic Arterial Hypertension (SAH) is frequently found in areas where the disease is endemic. The pathogenesis of patients with both pathologies (CCHD-SAH) is unsettled. Nitric Oxide (NO) and Kinins are important players in the myocardial inflammation process in experimental CCHD. No previous study has addressed this question in patients with CCHD, particularly in those with CCHD-SAH. Accordingly, this study was undertaken in an attempt to contribute to the understanding of the pathogenesis of patients with CCHD-SAH. METHODS: Thirty-seven patients with a positive serology for Chagas disease were enrolled; 15 had CCHD alone, 22 had CCHD-SAH (abnormal ECG/Doppler echocardiogram plus a systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg on admission), and 11 had SAH alone. Thirty healthy individuals matched by age and sex served as controls. Plasma High-molecular (Hkg) and low-molecular weight (LKg) kininogens, plasma kallikrein levels (Pkal and Tcal), Kininase II, and plasma NO were measured. RESULTS: HKg and LKg were lower in CCHD-SAH patients in comparison with other groups (P < .0001). Pkal and Tcal were higher in CCHD-SAH patients in comparison with the other groups (P< .0001). Kininase II levels were similar in SAH, CCHD, and CCHD-SAH patients, but lower in comparison with controls (P< .0001). NO levels were similar in CCHD and CCHD-SAH patients, but higher in comparison with SAH patients and controls (P > .0001). CONCLUSION: Such findings suggest increased Kinin and NO activity in patients with CCHD-SAH, thus contributing to the understanding of the pathogenesis of this condition.


Assuntos
Pressão Arterial , Doença de Chagas/sangue , Hipertensão/sangue , Cininas/sangue , Óxido Nítrico/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Brasil/epidemiologia , Estudos de Casos e Controles , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Doença de Chagas/fisiopatologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Regulação para Cima
3.
Am J Trop Med Hyg ; 103(2): 745-751, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32431281

RESUMO

Chronic Chagas disease can progress to myocardial involvement with intense fibrosis, which may predispose patients to sudden cardiac death through ventricular arrhythmia. The associations of myocardial fibrosis detected by cardiac magnetic resonance (CMR) parameters with non-sustained ventricular tachycardia (NSVT) were evaluated. This cross-sectional study included patients in early stages of Chagas disease (n = 47) and a control group (n = 15). Patients underwent cardiac evaluation, including CMR examination. Myocardial fibrosis assessment by CMR with measurement of late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV) was performed. There was an increase in myocardial fibrosis CMR parameters and ventricular arrhythmias among different stages of Chagas disease, combined with a decrease in the left ventricular ejection fraction (LVEF) by CMR and also in the right ventricular systolic function by S' wave on tissue Doppler. Fibrosis mass and ECV were associated with the Rassi score, ventricular extrasystole, and E/e' ratio in a logistic regression model adjusted for age and gender. The ECV maintained an association with the presence of NSVT, even after adjustments for fibrosis mass and LVEF assessed by CMR. The receiver-operating characteristic area under the curve for global ECV (0.85; 95% CI: 0.71-0.99) and NSVT was greater than that for fibrosis mass (0.75; 95% CI: 0.54-0.96), although this difference was not statistically significant. Extracellular volume could be an early marker of increased risk of ventricular arrhythmia in Chagas disease, presenting an independent association with NSVT in the initial stages of chronic Chagas cardiomyopathy, even after adjustment for fibrosis mass and LVEF.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Coração/diagnóstico por imagem , Taquicardia Ventricular/fisiopatologia , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/diagnóstico por imagem , Doença de Chagas/complicações , Doença de Chagas/diagnóstico por imagem , Doença de Chagas/fisiopatologia , Estudos Transversais , Ecocardiografia , Eletrocardiografia Ambulatorial , Espaço Extracelular , Feminino , Fibrose , Humanos , Modelos Logísticos , Imagem por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Tamanho do Órgão , Curva ROC , Volume Sistólico , Taquicardia Ventricular/etiologia , Função Ventricular Direita
4.
Rev Soc Bras Med Trop ; 53: e20190457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130325

RESUMO

INTRODUCTION: Chagas disease is one of the most common diseases in Latin America and heart involvement is the main cause of death. This study aimed to determine differences in tissue Doppler imaging (TDI) parameters in the assessment left and right ventricular function in patients with the indeterminate form of Chagas disease compared to those in healthy controls. METHODS: We compared 194 patients with the indeterminate form of Chagas disease to 72 age-matched healthy individuals. We considered p-values <0.05 to be statistically significant. RESULTS: TDI analysis of the right ventricular (RV) showed lengthened isovolumic relaxation time (IRT) and higher RV index of myocardial performance (RIMP) and left ventricle (LV) index of myocardial performance (LIMP) in the Chagas group than in the control group, indicating RV and LV systolic and diastolic myocardial damage. TDI analysis of the myocardial velocities of the interventricular septum and the lateral wall of the LV also showed a systolic and diastolic myocardial damage. CONCLUSIONS: The study results demonstrated early LV systolic and diastolic myocardial damage in the RV and LV in patients with the indeterminate form of Chagas disease by TDI. These early findings of RV and LV dysfunction may help identify patients who will progress to heart failure during the disease course. TDI should be included in initial patient evaluations because it allows adequate follow-up and treatment.


Assuntos
Doença de Chagas/fisiopatologia , Coração/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Estudos de Casos e Controles , Doença de Chagas/diagnóstico por imagem , Diagnóstico Precoce , Ecocardiografia , Ecocardiografia Doppler , Feminino , Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Disfunção Ventricular Esquerda/diagnóstico por imagem
5.
Mem Inst Oswaldo Cruz ; 115: e190364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130371

RESUMO

Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doença de Chagas/fisiopatologia , Fator VIIa/análise , Fígado/fisiopatologia , Proteína C/análise , Doença Aguda , Adulto , Biomarcadores/sangue , Brasil/epidemiologia , Estudos de Casos e Controles , Doença de Chagas/sangue , Doença de Chagas/enzimologia , Doença de Chagas/transmissão , Feminino , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Carga Parasitária , Estudos Prospectivos
6.
Artigo em Inglês | MEDLINE | ID: mdl-32074218

RESUMO

Proinflammatory and inflammatory mediators induced by Trypanosoma cruzi infection increase the oxidative stress, generating toxicity for cells targeting mitochondria of different tissues. We studied the activity of citrate synthase and complexes I-IV of respiratory chain in mitochondria of blood lymphomonocyte fraction, from albino Swiss mice infected with different isolates of T. cruzi , during Chagas disease evolution. Complexes I-IV were modified in infected groups (p<0.05) in all the stages, and an inflammatory process of different magnitudes was detected in the heart and skeletal muscle according to the isolate. The citrate synthase activity presented modifications in the SGO Z12 and the Tulahuen group (p<0.05). Hearts showed fiber fragmentation and fibrosis; skeletal muscle presented inflammatory infiltrates and in the Tulahuen infected group, there were also amastigote nests. The inflammatory processes produced an oxidative stress that induced different alterations of mitochondrial enzymes activities in the lymphomonocyte fraction that can be detected by a simple blood extraction, suggesting that they could be used as disease markers, especially in the indeterminate phase of Chagas disease.


Assuntos
Doença de Chagas/enzimologia , Citrato (si)-Sintase/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Mitocôndrias/enzimologia , Animais , Doença de Chagas/metabolismo , Doença de Chagas/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Masculino , Mitocôndrias/parasitologia , Mitocôndrias/patologia , Parasitemia
7.
Clin Immunol ; 212: 108346, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31954803

RESUMO

Previous studies showed that circulating autoantibodies against M2 muscarinic receptors (anti-M2R Ab) are associated with decreased cardiac parasympathetic modulation in patients with chronic Chagas disease (CD). Here we investigated whether the exposure of M2R to such antibodies could impair agonist-induced receptor activation, leading to the inhibition of associated signaling pathways. Preincubation of M2R-expressing HEK 293T cells with serum IgG fractions from chagasic patients with cardiovascular dysautonomia, followed by the addition of carbachol, resulted in the attenuation of agonist-induced Gi protein activation and arrestin-2 recruitment. These effects were not mimicked by the corresponding Fab fractions, suggesting that they occur through receptor crosslinking. IgG autoantibodies did not enhance M2R/arrestin interaction or promote M2R internalization, suggesting that their inhibitory effects are not likely a result of short-term receptor regulation. Rather, these immunoglobulins could function as negative allosteric modulators of acetylcholine-mediated responses, thereby contributing to the development of parasympathetic dysfunction in patients with CD.


Assuntos
Autoanticorpos/imunologia , Doenças do Sistema Nervoso Autônomo/imunologia , Doença de Chagas/imunologia , Receptor Muscarínico M2/imunologia , Adulto , Idoso , Regulação Alostérica , Autoanticorpos/metabolismo , Autoanticorpos/farmacologia , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/metabolismo , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Carbacol/farmacologia , Doença de Chagas/complicações , Doença de Chagas/metabolismo , Doença de Chagas/fisiopatologia , Agonistas Colinérgicos/farmacologia , Feminino , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Receptor Muscarínico M2/efeitos dos fármacos , Receptor Muscarínico M2/metabolismo , beta-Arrestina 1/metabolismo
8.
Gen Comp Endocrinol ; 289: 113380, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891689

RESUMO

Within invertebrates, the kinin family of neuropeptides is responsible for the modulation of a host of physiological and behavioural processes. In Rhodnius prolixus, kinins are primarily responsible for eliciting myotropic effects on various feeding and diuresis-related tissues. Here, the R. prolixus kinin receptor (RhoprKR) has been identified, cloned and sequenced from the central nervous system (CNS) and hindgut of R. prolixus. Sequence analyses show high similarity and identity between RhoprKR and other cloned invertebrate kinin receptors. The expression profile of RhoprKR shows the RhoprKR transcript throughout the R. prolixus gut, with highest expression in the hindgut, suggesting a role of Rhopr-kinins in various aspects of feeding and digestion. RNA interference (RNAi)-mediated knockdown of the RhoprKR transcript resulted in a significant reduction of hindgut contractions in response to Rhopr-kinin 2 and an Aib-containing kinin analog. dsRhoprKR- injected insects also consumed a significantly larger meal, suggesting a role of Rhopr-kinins in satiety.


Assuntos
Doença de Chagas/fisiopatologia , Cininas/metabolismo , Rhodnius/química , Animais , Feminino , Masculino
9.
Sci Rep ; 9(1): 18786, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827221

RESUMO

The objective of this investigation was to evaluate the activity of the suprahyoid musculature during swallowing and to correlate the findings with the degree of megaesophagus, oral and pharyngeal videofluoroscopy and esophageal manometry in patients with achalasia caused by Chagas' disease. Twenty-nine patients with positive serology for Trypanosoma cruzi and dysphagia (Chagas' disease group) and 29 individuals matched by sex and age (control group) participated in the study. Surface electromyography of the suprahyoid musculature and videofluoroscopy during swallowing of paste and liquid consistencies were performed. Canonical correlation analysis of the MANOVA test results showed that the Chagas' disease group had lower electromyographic activity when compared with controls. Overlapping circles of radiological findings were found for megaesophagus. The Spearman test showed a positive correlation between the electromyographic activity in the maximum voluntary isometric contraction and the time of pharyngeal transit for both liquid (p = 0.014) and paste (p = 0.047). The logistic regression test showed no association between electromyographic activity of the suprahyoid muscles and esophageal manometry results (p > 0.05). In conclusion, individuals with chagasic megaesophagus have reduced electromyographic activity of the suprahyoid muscles during swallowing, in addition to a greater recruitment of the suprahyoid musculature with increased pharyngeal transit time.


Assuntos
Doença de Chagas/fisiopatologia , Acalasia Esofágica/fisiopatologia , Músculos do Pescoço/fisiopatologia , Idoso , Deglutição , Eletromiografia , Esôfago/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
PLoS One ; 14(8): e0220689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374101

RESUMO

An ever-increasing number of patients with chronic indeterminate Chagas disease are diagnosed with early vascular and cardiac abnormalities, as cardiovascular imaging becomes more sensitive. However, the currently available information on aortic stiffness (a prognostic marker for adverse cardiovascular outcomes) in these patients is scarce. In this study, we consecutively recruited 21 asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease and 14 Bolivian adults, who were seronegative for Trypanosoma cruzi infection. No participants had a prior history of heart disease, hypertension, diabetes, chronic kidney disease or atrial fibrillation. Carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), carotid intima-media thickness and conventional echocardiographic measurements were recorded in all participants. Patients with chronic indeterminate Chagas disease had significantly higher cf-PWV (7.9±1.3 vs. 6.4±1.1 m/s, p = 0.003) and greater HOMA-estimated insulin resistance than subjects without Chagas disease. The two groups did not significantly differ in terms of age, sex, smoking, adiposity measures, blood pressure, plasma lipids, fasting glucose levels as well as cr-PWV, carotid intima-media thickness measurements, left ventricular mass and function. Presence of chronic indeterminate Chagas disease was significantly associated with increasing cf-PWV values (ß coefficient: 1.31, 95% coefficient interval 0.44 to 2.18, p = 0.005), even after adjustment for age, sex, heart rate, systolic blood pressure and insulin resistance. In conclusion, asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease have an early and marked increase in aortic stiffness, as measured by cf-PWV, when compared to Bolivian adults who were seronegative for Trypanosoma cruzi infection.


Assuntos
Pressão Sanguínea/fisiologia , Doença de Chagas/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Bolívia , Espessura Intima-Media Carotídea , Velocidade da Onda de Pulso Carótido-Femoral , Doença de Chagas/diagnóstico por imagem , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso
11.
Parasitology ; 146(13): 1655-1664, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31362797

RESUMO

Considering a potential exercise-drug interaction, we investigated whether exercise training could improve the efficacy of specific antiparasitic chemotherapy in a rodent model of Chagas disease. Wistar rats were randomized into five groups: sedentary and uninfected (CT); sedentary and infected (SI); sedentary, infected and treated (SIT); trained and infected (TI); trained, infected and treated (TIT). After 9-weeks running training, the animals were infected with T. cruzi and followed up for 4 weeks, receiving 100 mg kg-1 day-1 benznidazole. No evidence of myocarditis was observed in CT animals. TI animals exhibited reduced parasitemia, myocarditis, and reactive tissue damage compared to SI animals, in addition to increased IFN-γ, IL-4, IL-10, heart non-protein antioxidant (NPA) levels and glutathione-s transferase activity (P < 0.05). The CT, SIT and TIT groups presented similar reductions in parasitemia, cytokines (IFN-γ, TNF-α, IL-4, IL-10, IL-17 and MCP-1), inflammatory infiltrate, oxidative heart damage and antioxidant enzymes activity compared to SI and TI animals, as well as reduced heart microstructural remodeling (P < 0.05). By modulating heart inflammation and redox metabolism, exercise training exerts a protective effect against T. cruzi infection in rats. However, the antiparasitic and cardioprotective effects of benznidazole chemotherapy are more pronounced, determining similar endpoints in sedentary and trained T. cruzi-infected rats.


Assuntos
Antiparasitários/uso terapêutico , Cardiotônicos/uso terapêutico , Doença de Chagas/tratamento farmacológico , Nitroimidazóis/uso terapêutico , Condicionamento Físico Animal , Animais , Doença de Chagas/fisiopatologia , Citocinas/imunologia , Modelos Animais de Doenças , Esquema de Medicação , Coração/fisiopatologia , Masculino , Miocardite , Parasitemia/tratamento farmacológico , Ratos , Ratos Wistar , Corrida , Trypanosoma cruzi/efeitos dos fármacos
12.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31354939

RESUMO

Trypanosoma cruzi, the etiologic agent of Chagas disease, causes a latent infection that results in cardiomyopathy. Infection with this pathogen is a major socio-economic burden in areas of endemic infection throughout Latin America. The development of chagasic cardiomyopathy is dependent on the persistence of this parasite in host tissues. Pathogenesis of this cardiomyopathy is multifactorial and research indicates that it includes microvascular dysfunction, immune responses to host and parasite antigens, and various vasoactive and lipid mediators produced by both the host and parasite. It has been demonstrated that T. cruzi persists in adipose tissue and uses fat as a nutritional niche in infected hosts. This chronic infection of adipose tissue plays an important role in the pathogenesis and persistence of this infection and involves mitochondrial stress responses as well as the production of various anti-inflammatory adipokines and pro-inflammatory cytokines by both white and brown adipose tissue. The changes in diet in endemic regions of infection have resulted in an epidemic of obesity that has significant implications for the pathogenesis of T. cruzi infection and the development of chagasic cardiomyopathy in infected humans.


Assuntos
Tecido Adiposo , Doença de Chagas , Estresse Oxidativo , Trypanosoma cruzi , Doença de Chagas/fisiopatologia , Citocinas/metabolismo , Humanos , Trypanosoma cruzi/patogenicidade
13.
Arq. bras. oftalmol ; 82(3): 183-188, May-June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001301

RESUMO

ABSTRACT Purpose: To test the hypothesis that Chagas disease predisposes to optic nerve and retinal nerve fiber layer alterations. Methods: We conducted a cross-sectional study including 41 patients diagnosed with Chagas disease and 41 controls, paired by sex and age. The patients underwent ophthalmologic examinations, including intraocular pressure measurements, optic nerve and retinal nerve fiber layer screening with retinography, optical coherence tomography, and standard automated perimetry. Results: All of the patients with Chagas disease had a recent cardiologic study; 15 (36.6%) had heart failure, 14 (34.1%) had cardiac form without left ventricular dysfunction, and 12 (29.3%) had indeterminate form. Optic nerve/retinal nerve fiber layer alterations were observed in 24 patients (58.5%) in the Chagas disease group and 7 controls (17.1%) (p£0.01). Among these, optic nerve pallor, optic nerve alterations suggestive of glaucoma, notch, peripapillary hemorrhage, and localized retinal nerve fiber layer defect were detected. Alterations were more prominent in patients with Chagas disease and heart failure (11 patients), although they also occurred in those with Chagas disease without left ventricular dysfunction (7 patients) and those with indeterminate form (6 patients). Optical coherence tomography showed that themean of the average retinal nerve fiber layer thickness measured 89 ± 9.7 mm, and the mean of retinal nerve fiber layer superior and inferior thickness measured 109 ± 17.5 and 113 ± 16.8 mm, respectively were lower in patients with Chagas disease. In controls, these values were 94 ± 10.6 (p=0.02); 117 ± 18.1 (p=0.04), and 122 ± 18.4 mm (p=0.03). Conclusion: Changes in optic nerve/ retinal nerve fiber layer were more prevalent in patients with Chagas disease.


RESUMO Objetivo: Testar a hipótese de que a doença de Chagas predispõe a alterações no nervo óptico e camada de fibras nervosas peripapilar. Métodos: Foi realizado um estudo transversal com 41 pacientes diagnosticados com doença de Chagas e 41 controles, pareados por sexo e idade. Os pacientes foram submetidos a exames oftalmológicos, incluindo medida da pressão intraocular, avaliação do nervo óptico e camada de fibras nervosas através de retinografia, tomografia de coerência óptica e perimetria automatizada padrão. Resultados: Todos os pacientes com doença de Chagas apresentavam estudo cardiológico recente; 15 pacientes (36,6%) apresentavam insuficiência cardíaca; 14 (34,1%) forma cardíaca sem disfunção de ventrículo esquerdo e 12 (29,3%), forma indeterminada. Alterações do nervo óptico/camada de fibras nervosas foram observadas em 24 pacientes (58,5%) do grupo com doença de Chagas e 07 controles (17,1%) (p£0,01). Dentre estas, palidez do nervo óptico, alterações do nervo óptico sugestivas de glaucoma, entalhe, hemorragia peripapilar e defeito da camada de fibras localizado foram detectados. As alterações foram mais proeminentes nos pacientes com doença de Chagas e insuficiência cardíaca (11 pacientes) embora também ocorressem naqueles com doença de Chagas sem disfunção de ventrículo esquerdo (7 pacientes) e com forma indeterminada (6 pacientes). A tomografia de coerência óptica mostrou que a média da espessura da camada de fibras nervosas da retina mediu 89 ± 9,7 mm), e a média da espessura da camada de fibras nervosas superior e inferior mediu 109 ± 17,5 e 113 ± 16,8 mm, respectivamente, foi menor em pacientes com doença de Chagas. Nos controles, esses valores foram de 94 ± 10,6 mm (p=0,02); 117 ± 18,1 (p=0,04) e 122 ± 18,4 mm (p=0,03). Conclusão: Alterações do nervo óptico/camada de fibras nervosas da retina foram mais prevalentes nos pacientes com doença de Chagas.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Nervo Óptico/patologia , Retina/patologia , Doença de Chagas/patologia , Fibras Nervosas/patologia , Nervo Óptico/fisiopatologia , Nervo Óptico/diagnóstico por imagem , Valores de Referência , Retina/fisiopatologia , Doenças Retinianas/etiologia , Doenças Retinianas/patologia , Estudos de Casos e Controles , Doenças do Nervo Óptico/fisiopatologia , Doenças do Nervo Óptico/patologia , Estudos Transversais , Análise de Variância , Doença de Chagas/complicações , Doença de Chagas/fisiopatologia , Tomografia de Coerência Óptica , Testes de Campo Visual , Pressão Intraocular
14.
Arq Bras Oftalmol ; 82(3): 183-188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116301

RESUMO

PURPOSE: To test the hypothesis that Chagas disease predisposes to optic nerve and retinal nerve fiber layer alterations. METHODS: We conducted a cross-sectional study including 41 patients diagnosed with Chagas disease and 41 controls, paired by sex and age. The patients underwent ophthalmologic examinations, including intraocular pressure measurements, optic nerve and retinal nerve fiber layer screening with retinography, optical coherence tomography, and standard automated perimetry. RESULTS: All of the patients with Chagas disease had a recent cardiologic study; 15 (36.6%) had heart failure, 14 (34.1%) had cardiac form without left ventricular dysfunction, and 12 (29.3%) had indeterminate form. Optic nerve/retinal nerve fiber layer alterations were observed in 24 patients (58.5%) in the Chagas disease group and 7 controls (17.1%) (p£0.01). Among these, optic nerve pallor, optic nerve alterations suggestive of glaucoma, notch, peripapillary hemorrhage, and localized retinal nerve fiber layer defect were detected. Alterations were more prominent in patients with Chagas disease and heart failure (11 patients), although they also occurred in those with Chagas disease without left ventricular dysfunction (7 patients) and those with indeterminate form (6 patients). Optical coherence tomography showed that themean of the average retinal nerve fiber layer thickness measured 89 ± 9.7 mm, and the mean of retinal nerve fiber layer superior and inferior thickness measured 109 ± 17.5 and 113 ± 16.8 mm, respectively were lower in patients with Chagas disease. In controls, these values were 94 ± 10.6 (p=0.02); 117 ± 18.1 (p=0.04), and 122 ± 18.4 mm (p=0.03). CONCLUSION: Changes in optic nerve/ retinal nerve fiber layer were more prevalent in patients with Chagas disease.


Assuntos
Doença de Chagas/patologia , Fibras Nervosas/patologia , Nervo Óptico/patologia , Retina/patologia , Idoso , Análise de Variância , Estudos de Casos e Controles , Doença de Chagas/complicações , Doença de Chagas/fisiopatologia , Estudos Transversais , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/fisiopatologia , Doenças do Nervo Óptico/patologia , Doenças do Nervo Óptico/fisiopatologia , Valores de Referência , Retina/diagnóstico por imagem , Retina/fisiopatologia , Doenças Retinianas/etiologia , Doenças Retinianas/patologia , Tomografia de Coerência Óptica , Testes de Campo Visual
15.
Life Sci ; 230: 141-149, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129142

RESUMO

When administered alone, preinfection exercise training and benznidazole-based chemotherapy induce cardioprotection in Chagas disease. However, the effect of concomitant exercise and benznidazole treatment is unknown. We investigated whether exercise and specific chemotherapy could interact to modulate parasitemia, inflammation, redox status and heart damage in a murine model of T. cruzi infection. Wistar rats were randomized into an uninfected control group (CNT) and four groups infected with T. cruzi: sedentary untreated (SUN) and treated (STR), and trained untreated (TUN) and treated (TTR). Running training was administered 5 days/week for 4 weeks. Treated animals concomitantly received 100 mg/kg/day benznidazole. Heart inflammation and reactive damage were not detected in CNT animals. Compared to SUN, TUN animals presented increased levels of parasitemia, myocarditis, nitric oxide, hydrogen peroxide, protein carbonyl, malondialdehyde, cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10 and IL-17), catalase, superoxide dismutase and glutathione reductase activity, as well as reduced heart non-protein antioxidant levels (P < 0.05). TTR animals exhibited higher levels of parasitemia, myocarditis, hydrogen peroxide, malondialdehyde, IFN-γ, TNF-α and IL-6 than STR animals (P < 0.05), which showed the lowest levels of all analyzed parameters compared to the other groups (P < 0.05). Our findings indicate that exercise aggravates acute infection. When concomitantly administered with benznidazole, exercise training impaired parasitic control and chemotherapy-induced cardioprotection in T. cruzi-infected rats. Considering that exercise training and T. cruzi infection constitute independent metabolic challenges, the negative effects of concomitant treatment are potentially related to the overlapping oxidative and immunoinflammatory demands of exercise and the infection itself.


Assuntos
Doença de Chagas/tratamento farmacológico , Doença de Chagas/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Antioxidantes/farmacologia , Cardiotônicos/metabolismo , Catalase/metabolismo , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/terapia , Citocinas/metabolismo , Modelos Animais de Doenças , Coração/fisiologia , Inflamação/metabolismo , Interleucina-10/metabolismo , Masculino , Miocardite/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Nitroimidazóis/farmacologia , Parasitemia/parasitologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Trypanosoma cruzi/patogenicidade , Fator de Necrose Tumoral alfa/metabolismo
16.
PLoS Negl Trop Dis ; 13(4): e0007324, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30995222

RESUMO

Chagas Disease (CD) is an anthropozoonosis caused by Trypanosoma cruzi. With complex pathophysiology and variable clinical presentation, CD outcome can be influenced by parasite persistence and the host immune response. Complement activation is one of the primary defense mechanisms against pathogens, which can be initiated via pathogen recognition by pattern recognition molecules (PRMs). Collectin-11 is a multifunctional soluble PRM lectin, widely distributed throughout the body, with important participation in host defense, homeostasis, and embryogenesis. In complex with mannose-binding lectin-associated serine proteases (MASPs), collectin-11 may initiate the activation of complement, playing a role against pathogens, including T. cruzi. In this study, collectin-11 plasma levels and COLEC11 variants in exon 7 were assessed in a Brazilian cohort of 251 patients with chronic CD and 108 healthy controls. Gene-gene interactions between COLEC11 and MASP2 variants were analyzed. Collectin-11 levels were significantly decreased in CD patients compared to controls (p<0.0001). The allele rs7567833G, the genotypes rs7567833AG and rs7567833GG, and the COLEC11*GGC haplotype were related to T. cruzi infection and clinical progression towards symptomatic CD. COLEC11 and MASP2*CD risk genotypes were associated with cardiomyopathy (p = 0.014; OR 9.3, 95% CI 1.2-74) and with the cardiodigestive form of CD (p = 0.005; OR 15.2, 95% CI 1.7-137), suggesting that both loci act synergistically in immune modulation of the disease. The decreased levels of collectin-11 in CD patients may be associated with the disease process. The COLEC11 variant rs7567833G and also the COLEC11 and MASP2*CD risk genotype interaction were associated with the pathophysiology of CD.


Assuntos
Doença de Chagas/genética , Doença de Chagas/fisiopatologia , Colectinas/genética , Epistasia Genética , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos de Casos e Controles , Colectinas/sangue , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
17.
Acta Trop ; 194: 36-40, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30898615

RESUMO

Chagas' disease (CD) is a zoonosis caused by the protozoan Trypanosoma cruzi. Besides being an important cause of cardiomyopathy, central nervous system (CNS) manifestations have also been reported in CD. Renin-Angiotensin System (RAS) plays a pathophysiological role in several brain disorders such as cerebrovascular and neurodegenerative diseases. A link between RAS and nitric oxide (NO) pathways has been described in CNS. For instance, Angiotensin-(1-7) increases NO expression in the brain, which may, in turn, help to control parasite load in response to T. cruzi infection. Herein, we investigated the levels of RAS components in the brain cortex in acute T. cruzi infection and the effect of L-NAME administration, an inhibitor of the enzyme NO synthase, in CNS infection and in RAS molecules. Male Holtzman rats were inoculated intraperitoneally with T. cruzi Y strain and received L-NAME or tap water from one day before the infection until 13 days post infection (dpi). Parasitemia was evaluated on alternate days from day 3 post-infection until day 13 in both T. cruzi infected groups. Histopathological analysis of the brain cortex was also performed. Brain cortex was collected from non-infected (controls) and infected rats at 13 dpi for RAS components assessment. Infected rats receiving L-NAME presented higher parasitemia, brain parasitism and inflammation compared with non-treated infected animals. The administration of L-NAME significantly decreased the levels of Angiotensin I Converting Enzyme 2 (ACE2). In conclusion, we provided preliminary evidence of the interaction between RAS and NO during the acute phase of T. cruzi infection.


Assuntos
Encéfalo/metabolismo , Encéfalo/parasitologia , Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Óxido Nítrico/metabolismo , Sistema Renina-Angiotensina/fisiologia , Trypanosoma cruzi/fisiologia , Animais , Doença de Chagas/fisiopatologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Trypanosoma cruzi/isolamento & purificação
18.
J Neurol Sci ; 400: 10-14, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30878634

RESUMO

BACKGROUND: Chagas disease (CD) and ischemic stroke (IS) have a significant but poorly understood correlation. There is paucity of evidence regarding secondary prophylaxis of IS and etiological causes. OBJECTIVES: To compare arterial stroke topography and the respective morbidities and mortality in patients with CD of undetermined and cardioembolic etiologies and with cardioembolic IS (atrial fibrillation [AF]). METHODS: We compared vascular topography and outcomes using data obtained from the electronic medical records of all patients with IS with either CD (with cardioembolic or undetermined etiology) or AF, admitted to SARAH Hospital Brasilia between 2009 and 2013. RESULTS: A total of 115 patients were investigated: 49 involving AF, 23 involving CD of unclear etiology, and 43 involving CD of cardioembolic etiology. Middle cerebral artery stroke was predominant in all groups, although more frequent in patients with CD of undetermined etiology. No significant difference was found in the arterial territories. Hemodynamic stroke was predominant among CD patients who experienced cardioembolic events. AF patients had worse modified Rankin scale scores upon admission and a higher mortality rate than CD patients in both categories. CONCLUSIONS: Stroke topography is not useful in determining the etiological diagnosis. Patients with AF and IS are more likely to have worse outcomes than are those with CD and IS. The autonomic nervous system could be affected in patients with CD.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Doença de Chagas/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Idoso , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/fisiopatologia , Estudos de Casos e Controles , Infarto Cerebral/epidemiologia , Infarto Cerebral/fisiopatologia , Doença de Chagas/epidemiologia , Doença de Chagas/fisiopatologia , Estudos de Coortes , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Tomografia Computadorizada por Raios X/métodos
19.
Curr Med Chem ; 26(36): 6519-6543, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30381063

RESUMO

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host's immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.


Assuntos
Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/fisiologia , Doença de Chagas/fisiopatologia , Trypanosoma cruzi/patogenicidade , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Doença Crônica/tratamento farmacológico , Progressão da Doença , Humanos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Nitroimidazóis/uso terapêutico , Fatores de Risco , Trypanosoma cruzi/efeitos dos fármacos
20.
J Pharmacol Exp Ther ; 368(1): 11-20, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30348750

RESUMO

Most patients acutely infected with Trypanosoma cruzi undergo short-term structural and functional cardiac alterations that heal without sequelae. By contrast, in patients whose disease progresses to chronic infection, irreversible degenerative chronic Chagas cardiomyopathy (CCC) may develop. To account for the contrast between cardiac regeneration in high-parasitism acute infection and progressive cardiomyopathy in low-parasitism CCC, we hypothesized that T. cruzi expresses repair factors that directly facilitate cardiac regeneration. We investigated, as one such repair factor, the T. cruzi parasite-derived neurotrophic factor (PDNF), known to trigger survival of cardiac myocytes and fibroblasts and upregulate chemokine chemokine C-C motif ligand 2, which promotes migration of regenerative cardiac progenitor cells (CPCs). Using in vivo and in vitro models of Chagas disease, we tested whether T. cruzi PDNF promotes cardiac repair. Quantitative PCR and flow cytometry of heart tissue revealed that stem-cell antigen-1 (Sca-1+) CPCs expand in acute infection in parallel to parasitism. Recombinant PDNF induced survival and expansion of ex vivo CPCs, and intravenous administration of PDNF into naïve mice upregulated mRNA of cardiac stem-cell marker Sca-1. Furthermore, in CCC mice, a 3-week intravenous administration of PDNF protocol induced CPC expansion and reversed left ventricular T-cell accumulation and cardiac remodeling including fibrosis. Compared with CCC vehicle-treated mice, which developed severe atrioventricular block, PDNF-treated mice exhibited reduced frequency and severity of conduction abnormalities. Our findings are in support of the novel concept that T. cruzi uses PDNF to promote mutually beneficial cardiac repair in Chagas disease. This could indicate a possible path to prevention or treatment of CCC.


Assuntos
Bloqueio Atrioventricular/sangue , Bloqueio Atrioventricular/terapia , Doença de Chagas/sangue , Doença de Chagas/terapia , Glicoproteínas/administração & dosagem , Glicoproteínas/sangue , Neuraminidase/administração & dosagem , Neuraminidase/sangue , Administração Intravenosa , Animais , Bloqueio Atrioventricular/fisiopatologia , Doença de Chagas/fisiopatologia , Chlorocebus aethiops , Doença Crônica , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Trypanosoma cruzi/metabolismo , Células Vero
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