RESUMO
BACKGROUND: Chagas disease is a systemic illness with widespread microvascular involvement. Experimental and clinical studies suggest that functional and structural microcirculatory abnormalities might be relevant to the disease progression. OBJECTIVES: To show the presence of sublingual microcirculatory alterations in patients with chronic Chagas disease. METHODS: This was a cross-sectional study including adult patients with serologic diagnosis of Chagas disease (n = 41) and control volunteers with negative serology (n = 38), from an endemic rural population. Study participants underwent clinical, electrocardiographic, echocardiographic, and sublingual videomicroscopic assessment. Videos were acquired by a sidestream-dark-field (SDF) imaging device and evaluated by a software-assisted analysis (AVA 3.2 software). FINDINGS: Most of Chagas disease patients were in the indeterminate phase (n = 34) and had lower heart rate and more echocardiographic abnormalities than control group (50 vs. 26%, p = 0.03). They also exhibited higher small microvessels total and perfused vascular density (20.12 ± 2.33 vs. 19.05 ± 2.25 and 20.03 ± 2.28 vs. 19.01 ± 2.25 mm/mm2, p < 0.05 for both). Other microvascular variables did not differ between groups. MAIN CONCLUSIONS: Patients with chronic Chagas disease exhibited increases in sublingual total and perfused microvascular density. Angiogenesis might be the underlying mechanism. The videomicroscopic assessment of mucosal sublingual microcirculation might be an additional tool in the monitoring of Chagas disease.
Assuntos
Doença de Chagas , Microcirculação , Soalho Bucal , População Rural , Humanos , Microcirculação/fisiologia , Estudos Transversais , Masculino , Feminino , Doença de Chagas/fisiopatologia , Adulto , Pessoa de Meia-Idade , Soalho Bucal/irrigação sanguínea , Estudos de Casos e Controles , Doença Crônica , Doenças EndêmicasRESUMO
Disorders of gastrointestinal motility are the major physiologic problem in chagasic megacolon. The contraction mechanism is complex and controlled by different cell types such as enteric neurons, smooth muscle, telocytes, and an important pacemaker of the intestine, the interstitial cells of Cajal (ICCs). The role of ICCs in the progression of acute and chronic Chagas disease remains unclear. In the present work, we investigate the aspects of ICCs in a long-term model of Chagas disease that mimics the pathological aspects of human megacolon. Different subsets of ICCs isolated from Auerbach's myenteric plexuses and muscle layers of control and Trypanosoma cruzi infected animals were determined by analysis of CD117, CD44, and CD34 expression by flow cytometer. Compared with the respective controls, the results showed a reduced frequency of mature ICCs in the acute phase and three months after infection. These results demonstrate for the first time the phenotypic distribution of ICCs associated with functional dysfunction in a murine model of chagasic megacolon. This murine model proved valuable for studying the profile of ICCs as an integrative system in the gut and as a platform for understanding the mechanism of chagasic megacolon development.
Assuntos
Doença de Chagas , Modelos Animais de Doenças , Células Intersticiais de Cajal , Megacolo , Animais , Células Intersticiais de Cajal/patologia , Doença de Chagas/patologia , Doença de Chagas/fisiopatologia , Megacolo/parasitologia , Megacolo/patologia , Megacolo/fisiopatologia , Camundongos , Citometria de Fluxo , Masculino , Trypanosoma cruzi/fisiologiaRESUMO
BACKGROUND: Chagas disease causes digestive anatomic and functional changes, including the loss of the myenteric plexus and abnormal esophageal radiologic and manometric findings. OBJECTIVE: To evaluate the association of abnormal esophageal radiologic findings, cardiac changes, distal esophageal contractions, and complaints of dysphagia and constipation in upper (UES) and lower (LES) esophageal sphincter basal pressure in Chagas disease patients. METHODS: The study evaluated 99 patients with Chagas disease and 40 asymptomatic normal volunteers. The patients had normal esophageal radiologic examination (n=61) or esophageal retention without an increase in esophageal diameter (n=38). UES and LES pressure was measured with the rapid pull-through method in a 4-channel water-perfused round catheter. Before manometry, the patients were asked about dysphagia and constipation and submitted to electrocardiography and chest radiography. RESULTS: The amplitude of esophageal distal contraction decreased from controls to chagasic patients with esophageal retention. The proportion of failed and simultaneous contractions increased in patients with abnormal radiologic examination (P<0.01). There were no significant differences in UES and LES pressure between the groups. UES pressure was similar between Chagas disease patients with cardiomegaly (n=27, 126.5±62.7 mmHg) and those without it (n=72, 144.2±51.6 mmHg, P=0.26). Patients with constipation had lower LES pressure (n=23, 34.7±20.3 mmHg) than those without it (n=76, 42.9±20.5 mmHg, P<0.03). CONCLUSION: Chagas disease patients with absent or mild esophageal radiologic involvement had no significant changes in UES and LES basal pressure. Constipation complaints are associated with decreased LES basal pressure.
Assuntos
Doença de Chagas , Transtornos da Motilidade Esofágica , Esfíncter Esofágico Inferior , Manometria , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doença de Chagas/fisiopatologia , Doença de Chagas/complicações , Esfíncter Esofágico Inferior/fisiopatologia , Esfíncter Esofágico Inferior/diagnóstico por imagem , Estudos de Casos e Controles , Transtornos da Motilidade Esofágica/fisiopatologia , Transtornos da Motilidade Esofágica/complicações , Adulto , Esfíncter Esofágico Superior/fisiopatologia , Esfíncter Esofágico Superior/diagnóstico por imagem , Constipação Intestinal/fisiopatologia , Constipação Intestinal/etiologia , Constipação Intestinal/diagnóstico por imagem , Idoso , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/diagnóstico por imagem , PressãoRESUMO
INTRODUCTION: Although Chagas disease causes high levels of morbidity, the muscle function and tolerance to physical activity in Chagas disease patients are still not completely understood. OBJECTIVE: To compare health-related fitness of patient groups with acute Chagas disease versus chronic Chagas disease. MATERIALS AND METHODS: We conducted a cross-sectional study involving 18 patients. The data were obtained from patient´s records, and functional capacity was measured with the sixminute walk test, the peripheral muscle strength with handgrip strength, and respiratory muscle strength using the maximum inspiratory pressure and the maximum expiratory pressure. RESULTS: The 18 patients were divided in two groups: acute Chagas disease (n=9) and chronic Chagas disease (n=9). The distance walked in the six-minute walk test was lower than the predicted distance walked in both groups (p < 0.0001). The maximum expiratory pressure was lower than the predicted one (p = 0.005), and statistically significant for chronic Chagas disease patients (p = 0.02). Heart rate increased faster in the chronic Chagas disease group within the first two minutes of the six-minute walk test (p = 0.04). The sixminute walk test in the acute Chagas disease group presented a strong correlation with peripheral muscle strength (p = 0.012) and maximum inspiratory pressure (p = 0.0142), while in the chronic Chagas disease group, only peripheral muscle strength and maximum inspiratory pressure were correlated (p = 0.0259). CONCLUSION: The results suggest lowered functional capacity and reduced respiratory and peripheral muscle strength in patients with Chagas disease, although no differences were observed between groups. The early increase in heart rate during exercise in the chronic Chagas disease group implies a greater myocardial overload.
Introducción. Aunque la enfermedad de Chagas causa gran morbilidad, la función muscular y la tolerancia a la actividad física de estos pacientes aún no se comprenden por completo. Objetivos. Comparar el estado físico relacionado con la salud de pacientes con enfermedad de Chagas aguda versus crónica de Chagas. Materiales y métodos. Se hizo un estudio transversal que incluyó 18 pacientes. La información se obtuvo de los registros de los pacientes. La capacidad funcional se evaluó con la prueba de la caminata de seis minutos, se determinó la fuerza de prensión manual para evaluar los músculos periféricos y se estableció la fuerza de los músculos respiratorios mediante presión inspiratoria máxima y la presión espiratoria máxima. Resultados. Se evaluaron 18 pacientes, nueve con enfermedad de Chagas aguda y nueve con enfermedad de Chagas crónica. La distancia recorrida en la prueba de caminata de seis minutos fue menor que la distancia recorrida predicha en ambos grupos (p < 0,0001). La presión espiratoria máxima fue más baja de lo previsto (forma aguda: p = 0,005; forma crónica: p = 0,02). La frecuencia cardíaca aumentó más rápido en el grupo con enfermedad de Chagas crónica dentro de los primeros dos minutos de la caminata (p = 0,04). La distancia recorrida en el grupo con la forma aguda se correlacionó con la fuerza de prensión manual (p = 0,01) y la presión inspiratoria máxima (p = 0,01). En el grupo con la enfermedad crónica, solo hubo correlación entre la fuerza de presión manual y la presión inspiratoria máxima (p = 0,02). Conclusiones. Los resultados sugirieren disminución de la capacidad funcional y de la fuerza muscular respiratoria y periférica, aunque sin diferencias entre ambos grupos. El aumento de la frecuencia cardiaca en el grupo con enfermedad de Chagas crónica sugiere una mayor sobrecarga miocárdica.
Assuntos
Doença de Chagas , Força Muscular , Humanos , Estudos Transversais , Doença Crônica , Doença Aguda , Doença de Chagas/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Teste de Caminhada , Músculos Respiratórios/fisiopatologia , Aptidão Física , Força da Mão , Idoso , Frequência Cardíaca/fisiologiaRESUMO
BACKGROUND: The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the preservation of mammalian homeostasis. This interplay involves two major pathways: the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. SUMMARY: The establishment of infection can affect immunoneuroendocrine interactions, with functional consequences for immune organs, particularly the thymus. Interestingly, the physiology of this primary organ is not only under the control of the central nervous system (CNS) but also exhibits autocrine/paracrine regulatory circuitries mediated by hormones and neuropeptides that can be altered in situations of infectious stress or chronic inflammation. In particular, Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), impacts upon immunoneuroendocrine circuits disrupting thymus physiology. Here, we discuss the most relevant findings reported in relation to brain-thymic connections during T. cruzi infection, as well as their possible implications for the immunopathology of human Chagas disease. KEY MESSAGES: During T. cruzi infection, the CNS influences thymus physiology through an intricate network involving hormones, neuropeptides, and pro-inflammatory cytokines. Despite some uncertainties in the mechanisms and the fact that the link between these abnormalities and chronic Chagasic cardiomyopathy is still unknown, it is evident that the precise control exerted by the brain over the thymus is markedly disrupted throughout the course of T. cruzi infection.
Assuntos
Encéfalo , Doença de Chagas , Timo , Humanos , Doença de Chagas/imunologia , Doença de Chagas/fisiopatologia , Animais , Encéfalo/imunologia , Timo/imunologia , Timo/fisiologia , Trypanosoma cruzi/fisiologia , Trypanosoma cruzi/imunologia , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Neuroimunomodulação/fisiologia , Neuroimunomodulação/imunologia , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
In insects, the follicle cells (FCs) give rise to a single-layered tissue of binucleated professional secretory cells that surround the oocytes during oogenesis. In the latest stage of oocyte development, the FCs rapidly synthesize and secrete the chorion (eggshell) immediately before degenerating through apoptosis. Here, we used RT-qPCR, electron microscopy, and RNAi silencing to explore the role of the main unfolded protein response (UPR) receptors IRE1 and PERK, as well as the ultrastructure dynamics of the FCs during oogenesis of the insect vector of Chagas disease Rhodnius prolixus. We found that IRE1 and PERK mRNAs are highly expressed in the ovaries of vitellogenic females. Interestingly, we observed that IRE1 and PERK, as well as different isoforms of the chaperones Bip and PDI, have their FCs gene expression levels decreased during the vitellogenesis to choriogenesis transition. Using transmission electron microscopy, we observed that the downregulation of the UPR gene expression is accompanied by dramatic changes in the FCs ultrastructure, with an 80% reduction in the mean area of the ER tubules, and circularization and enlargement of the mitochondria. Additionally, we found that parental RNAi silencing of both IRE1 and PERK resulted in minor changes in the chorion protein composition and ultrastructure, accessed by urea extraction of the chorion proteins and scanning electron microscopy, respectively, but did not impact the overall levels of oviposition and F1 embryo development.
Assuntos
Doença de Chagas/genética , Retículo Endoplasmático/metabolismo , Endorribonucleases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Vitelogênese/genética , eIF-2 Quinase/metabolismo , Animais , Doença de Chagas/fisiopatologia , Regulação para Baixo , Feminino , Insetos , RhodniusRESUMO
BACKGROUND: Left ventricular systolic dysfunction (LVSD) in Chagas disease (ChD) is relatively common and its treatment using low-cost drugs can improve symptoms and reduce mortality. Recently, an artificial intelligence (AI)-enabled ECG algorithm showed excellent accuracy to detect LVSD in a general population, but its accuracy in ChD has not been tested. OBJECTIVE: To analyze the ability of AI to recognize LVSD in patients with ChD, defined as a left ventricular ejection fraction determined by the Echocardiogram ≤ 40%. METHODOLOGY/PRINCIPAL FINDINGS: This is a cross-sectional study of ECG obtained from a large cohort of patients with ChD named São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) Study. The digital ECGs of the participants were submitted to the analysis of the trained machine to detect LVSD. The diagnostic performance of the AI-enabled ECG to detect LVSD was tested using an echocardiogram as the gold standard to detect LVSD, defined as an ejection fraction <40%. The model was enriched with NT-proBNP plasma levels, male sex, and QRS ≥ 120ms. Among the 1,304 participants of this study, 67% were women, median age of 60; there were 93 (7.1%) individuals with LVSD. Most patients had major ECG abnormalities (59.5%). The AI algorithm identified LVSD among ChD patients with an odds ratio of 63.3 (95% CI 32.3-128.9), a sensitivity of 73%, a specificity of 83%, an overall accuracy of 83%, and a negative predictive value of 97%; the AUC was 0.839. The model adjusted for the male sex and QRS ≥ 120ms improved the AUC to 0.859. The model adjusted for the male sex and elevated NT-proBNP had a higher accuracy of 0.89 and an AUC of 0.874. CONCLUSION: The AI analysis of the ECG of Chagas disease patients can be transformed into a powerful tool for the recognition of LVSD.
Assuntos
Inteligência Artificial , Doença de Chagas/complicações , Eletrocardiografia/métodos , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Algoritmos , Brasil , Doença de Chagas/fisiopatologia , Estudos Transversais , Eletrocardiografia/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Função Ventricular EsquerdaRESUMO
BACKGROUND: Chagas disease remains a major cause of cardiovascular death in endemic areas. Focused echocardiography (FoCUS) is a point-of-care means of assessing cardiac function which can be useful for the diagnosis of cardiac involvement. OBJECTIVE: This study aims evaluating the characteristics of validity and reliability of FoCUS applied on Chagas disease patients. METHODS: Patients with Chagas disease coming from an endemic area were selected from a large cohort (SaMi-Trop). A simplified echocardiogram with only three images was extracted from the conventional echocardiogram performed in this cohort. The images were evaluated by an observer who was blinded to the clinical and echocardiographic data, to determine the accuracy and reliability of FoCUS for cardiac assessment. The analysis constituted of 5 prespecified variables, dichotomized in absence or presence: left ventricular (LV) size and systolic function, right ventricular (RV) size and systolic function, and LV aneurysm. RESULTS: We included 725 patients with a mean age of 63.4 ± 12.3 years, 483 (67%) female. Abnormal electrocardiogram was observed in 81.5% of the patients. Left and right ventricular dysfunctions were found in 103 (14%) and 49 (7%) of the patients, respectively. Sensitivity, specificity, positive predictive value and negative predictive value were 84%, 94%, 70% and 97% for LV enlargement and 81%, 93%, 68% and 97% for LV systolic dysfunction, respectively, and 46%, 99%, 60% and 98% for RV dilatation, and 37%, 100%, 100% and 96% for RV dysfunction, respectively. Inter and intraobserver agreement were 61% and 87% for LV enlargement and 63% and 92% for LV dysfunction, respectively, and 50% and 49% for RV size and 46% and 79% for RV dysfunction, respectively. LV apical aneurysm was found in 45 patients (6.2%) with the lowest sensitivity of FoCUS study (11%; 95% CI 2-28%). CONCLUSIONS: FoCUS showed satisfactory values of validity and reliability for assessment of cardiac chambers in patients with Chagas disease, except for apical aneurysm. This tool can identify heart disease with potential impact on patient management in the limited-resource setting.
Assuntos
Doença de Chagas/diagnóstico , Ecocardiografia , Coração/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Direita/diagnóstico , Idoso , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/diagnóstico por imagem , Cardiomiopatia Chagásica/fisiopatologia , Doença de Chagas/diagnóstico por imagem , Doença de Chagas/fisiopatologia , Feminino , Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Sístole/fisiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/fisiopatologiaRESUMO
BACKGROUND: In the Brazilian Amazon, a new epidemiological profile of Chagas disease transmission, the oral route, has been detected and cited as being responsible for the increase in acute cases in Brazil. The clinical evaluation of acute Chagas disease (ACD) has been a challenge since it can progress to a chronic phase with cardiac alterations, and the follow-up by modern diagnostic methods is very difficult due to the socio-geographical characteristics of the Brazilian Amazon. Thus, alternatives should be sought to alleviate this problem. We conducted a study to evaluate subjects with ACD using the 12-lead ECG QRS score (Selvester score) as an estimative of myocardial injury progression before and after ACD treatment. METHODS: The study included indigenous subjects from the Amazon region with ACD in clinical follow-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) Chagas Disease outpatient clinic in the state of Amazonas, Brazil. The control group consisted of 31 healthy volunteers with no history of heart disease and no reactive serology for Chagas disease. Baseline ECG was performed in all subjects. The Selvester scoring method was performed according to the standardized guide (< 3 points: no myocardial injury,> 3: points × 3% = % of the predicted LV infarction). RESULTS: A total of 62 subjects were included, 31 as cases and 31 as controls. The mean follow-up of the case group was 17 months. The control group presented normal ECG. The case group presented 13 alterations before treatment and 11 after. Nineteen individuals presented scores > 3 points, 6 before and 13 after. In 19.36% of subjects, myocardial injury was found before treatment and in 41.94% after treatment. CONCLUSION: This is the first study that uses the Selvester score (SS) to predict myocardial injury in subjects with ACD. The results of this study suggest the significant presence of myocardial injury from the beginning of treatment to the period post treatment of ACD, which demonstrates that the SS can be applied for stratification and follow-up of Chagas disease in the Amazon region.
Assuntos
Doença de Chagas/fisiopatologia , Eletrocardiografia/métodos , Coração/fisiopatologia , Adulto , Brasil/etnologia , Doença de Chagas/complicações , Doença de Chagas/tratamento farmacológico , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Coração/diagnóstico por imagem , Humanos , Povos Indígenas , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Megacolon is one of the main late complications of Chagas disease, affecting approximately 10% of symptomatic patients. However, studies are needed to understand the mechanisms involved in the progression of this condition. During infection by Trypanosoma cruzi (T. cruzi), an inflammatory profile sets in that is involved in neural death, and this destruction is known to be essential for megacolon progression. One of the proteins related to the maintenance of intestinal neurons is the type 2 bone morphogenetic protein (BMP2). Intestinal BMP2 homeostasis is directly involved in the maintenance of organ function. Thus, the aim of this study was to correlate the production of intestinal BMP2 with immunopathological changes in C57Bl/6 mice infected with the T. cruzi Y strain in the acute and chronic phases. The mice were infected with 1000 blood trypomastigote forms. After euthanasia, the colon was collected, divided into two fragments, and a half was used for histological analysis and the other half for BMP2, IFNγ, TNF-α, and IL-10 quantification. The infection induced increased intestinal IFNγ and BMP2 production during the acute phase as well as an increase in the inflammatory infiltrate. In contrast, a decreased number of neurons in the myenteric plexus were observed during this phase. Collagen deposition increased gradually throughout the infection, as demonstrated in the chronic phase. Additionally, a BMP2 increase during the acute phase was positively correlated with intestinal IFNγ. In the same analyzed period, BMP2 and IFNγ showed negative correlations with the number of neurons in the myenteric plexus. As the first report of BMP2 alteration after infection by T. cruzi, we suggest that this imbalance is not only related to neuronal damage but may also represent a new route for maintaining the intestinal proinflammatory profile during the acute phase.
Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Doença de Chagas/metabolismo , Interferon gama/metabolismo , Animais , Proteína Morfogenética Óssea 2/genética , Doença de Chagas/fisiopatologia , Colo/patologia , Modelos Animais de Doenças , Interleucina-10/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/patologia , Masculino , Megacolo/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Plexo Mientérico/metabolismo , Neurônios/metabolismo , Trypanosoma cruzi/patogenicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Memory impairment has been associated with chronic Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. In degenerative diseases, memory loss has been associated with increased oxidative stress, revealed as enhanced lipid peroxidation, in the cerebral cortex. Benznidazole (Bz), a trypanocidal drug efficient to reduce blood parasite load in the acute and chronic phases of infection, showed controversial effects on heart disease progression, the main clinical manifestation of CD. Here, we evaluated whether C57BL/6 mice infected with the Colombian type I T. cruzi strain present memory deficit assessed by (i) the novel object recognition task, (ii) the open field test and (iii) the aversive shock evoked test, at 120 days post infection (dpi). Next, we tested the effects of Bz therapy (25mg/Kg/day, for 30 consecutive days) on memory evocation, and tried to establish a relation between memory loss, parasite load and oxidative stress in the central nervous system (CNS). At 120 dpi, T. cruzi-infected mice showed memory impairment, compared with age-matched non-infected controls. Bz therapy (from 120 to 150 dpi) hampered the progression of habituation and aversive memory loss and, moreover, reversed memory impairment in object recognition. In vehicle-administered infected mice, neuroinflammation was absent albeit rare perivascular mononuclear cells were found in meninges and choroid plexus. Bz therapy abrogated the infiltration of the CNS by inflammatory cells, and reduced parasite load in hippocampus and cerebral cortex. At 120 and 150 dpi, lipid peroxidation was increased in the hippocampus and cortex tissue extracts. Notably, Bz therapy reduced levels of lipid peroxidation in the cerebral cortex. Therefore, in experimental chronic T. cruzi infection Bz therapy improved memory loss, in association with reduction of parasite load and oxidative stress in the CNS, providing a new perspective to improve the quality of life of Chagas disease patients.
Assuntos
Doença de Chagas/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Nitroimidazóis/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Animais , Doença de Chagas/complicações , Doença de Chagas/metabolismo , Doença de Chagas/fisiopatologia , Doença Crônica , Cognição/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Feminino , Camundongos Endogâmicos C57BL , Carga ParasitáriaRESUMO
Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosoma cruzi that affects several million people mainly in Latin American countries. Chagas disease has two phases, which are acute and chronic, both separated by an indeterminate time period in which the infected individual is relatively asymptomatic. The acute phase extends for 40-60 days with atypical and mild symptoms; however, about 30% of the infected patients will develop a symptomatic chronic phase, which is characterized by either cardiac, digestive, neurological, or endocrine problems. Cardiomyopathy is the most important and severe result of Chagas disease, which leads to left ventricular systolic dysfunction, heart failure, and sudden cardiac death. Most deaths are due to heart failure (70%) and sudden death (30%) resulting from cardiomyopathy. During the chronic phase, T. cruzi-infected macrophages respond with the production of proinflammatory cytokines and production of superoxide and nitric oxide by the NADPH oxidase 2 (NOX2) and inducible nitric oxide synthase (iNOS) enzymes, respectively. During the chronic phase, myocardial changes are produced as a result of chronic inflammation, oxidative stress, fibrosis, and cell death. The cellular inflammatory response is mainly the result of activation of the NF-κB-dependent pathway, which activates gene expression of inflammatory cytokines, leading to progressive tissue damage. The persisting production of reactive oxygen species (ROS) is the result of mitochondrial dysfunction in the cardiomyocytes. In this review, we will discuss inflammation and oxidative damage which is produced in the heart during the chronic phase of Chagas disease and recent evidence on the role of macrophages and the production of proinflammatory cytokines during the acute phase and the origin of macrophages/monocytes during the chronic phase of Chagas disease. We will also discuss the contributing factors and mechanisms leading to the chronic inflammation of the cardiac tissue during the chronic phase of the disease as well as the innate and adaptive host immune response. The contribution of genetic factors to the progression of the chronic inflammatory cardiomyopathy of chronic Chagas disease is also discussed. The secreted extracellular vesicles (exosomes) produced for both T. cruzi and infected host cells can play key roles in the host immune response, and those roles are described. Lastly, we describe potential treatments to attenuate the chronic inflammation of the cardiac tissue, designed to improve heart function in chagasic patients.
Assuntos
Doença de Chagas/genética , Exossomos/metabolismo , Inflamação/fisiopatologia , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , Animais , Doença de Chagas/fisiopatologia , Doença Crônica , Humanos , CamundongosRESUMO
Chagas disease (ChD) and systemic arterial hypertension (SAH) are two severe comorbidities that lead to mortality and a reduction in people's quality of life, with an impact on public health. The aim of this study was to quantify the biomarkers of cardiac injury in patients with ChD and SAH. Eighty patients were divided into four groups: 20 hypertensive patients, 20 ChD-hypertensive patients, 20 ChD patients, and 20 normotensive volunteers; all of them came from outpatient's public health services. Among the evaluated markers for cardiac lesions (creatine kinase, creatine kinase-MB isoform, myoglobin, high-sensitive cardiac troponin T[hs-cTnT], B-type natriuretic peptide [BNP], and C-reactive protein), hs-cTnT and BNP were the most appropriate. Importantly, our results showed that the cut off point for hs-cTnT could be < 0.007 ng/mL, which could lead to the early detection of myocardial lesions. The BNP and hs-cTnT levels were high only in the ChD and ChD-hypertensive patient groups, suggesting that Chagas' disease may play an important role in the increase of these biomarkers. ChD patients, hypertensive or not, with cardiac or cardiodigestive involvement presented significantly higher values of hs-cTnT (p < 0.001) and BNP (p = 0.001) than ChD patients with indeterminate and digestive forms, which strengthens the validation of these markers for the follow-up of clinical cardiac form of ChD. This study suggests that the BNP and hs-cTnT can be used as possible indirect biomarkers of cardiac damage. In addition, the reference values of these biomarkers in Chagas and hypertensive cardiomyopathies should be better understood with further studies.
Assuntos
Doença de Chagas/diagnóstico , Hipertensão/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Doença de Chagas/fisiopatologia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Valor Preditivo dos Testes , Qualidade de Vida , Curva ROC , Troponina T/sangueRESUMO
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 CimaRESUMO
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-IdadeRESUMO
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 , Imageamento 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 DireitaRESUMO
BACKGROUND: Distal contractile integral (DCI) is influenced by factors other than esophageal smooth muscle contractility, such as intrabolus pressure and vascular and respiratory movements' artifacts. We aimed to determine the size of the contribution of pressures generated by vascular compression on the esophagus to the DCI measured in HRM recordings in symptomatic patients. METHODS: HRM manometry recordings obtained from 383 subjects referred to the GI motility laboratory at a tertiary center (2012-2016) were evaluated by visual inspection for evidence of strong vascular compression (SVC) of the esophagus. Clinical, demographic, manometric, and serologic data for Chagas disease were obtained. Subjects were classified, respectively, as asymptomatics (ASYM) or symptomatics (SYMP). DCI and SVC-DCI were measured, and the SVC-DCI/DCI ratio was expressed as a percentage and the difference between DCI and SVC-DCI (neat-DCI) was calculated. DCI, SVC-DCI, SVC-DCI/DCI % and neat-DCI from SYMP and ASYM were compared. RESULTS: SVC was conspicuous in 42 of 383 subjects (11%). In 33 subjects, SVC was detected only in supine position. SVC was localized in middle esophagus in 21 subjects (50%), in distal esophagus in 12 subjects (29%) and in both regions in 9 subjects (21%). In 9 subjects, SVC vanished from the swallowing window analysis (21%). CONCLUSIONS: SVC is a common finding in esophageal HRM study, particularly in the supine position. Occasionally, its contribution to DCI value is sufficiently great to masquerade esophageal hypocontractility. Different manometric protocols may be required in patients with SVC.
Assuntos
Doença de Chagas/fisiopatologia , Transtornos da Motilidade Esofágica/fisiopatologia , Esôfago/irrigação sanguínea , Manometria/métodos , Contração Muscular/fisiologia , Adulto , Artefatos , Estudos de Casos e Controles , Doença de Chagas/sangue , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Deglutição/fisiologia , Transtornos da Motilidade Esofágica/diagnóstico , Esôfago/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/fisiologia , Peristaltismo/fisiologia , Pressão/efeitos adversos , PrevalênciaRESUMO
A doença de Chagas ainda é uma doença tropical muito prevalente no Brasil. Pode apresentar duas fases (aguda e crônica) e exibe grandes repercussões, sobretudo as que envolvem o sistema nervoso periférico e/ou central. Com o aumento do número de pessoas vivendo em estado (transitório ou permanente) de imunossupressão, os casos de manifestações neurológicas por neurochagas aumentaram, e este tornou-se um importante diagnóstico diferencial com outras doenças oportunistas. Este artigo teve como objetivo revisar os principais aspectos clínicos e terapêuticos da doença de Chagas no sistema nervoso central.
Chagas disease is still a very prevalent tropical disease in Brazil. It can have two phases - acute and chronic and shows major repercussions, especially those involving the peripheral and/ or central nervous system. With the increase in the number of people living in the (transient or permanent) state of immunosuppression the cases of neurological manifestations of Chagas disease increased and this became an important differential diagnosis with other opportunistic diseases. This article aimed to review the main clinical and therapeutic aspects of central nervous system Chagas disease
Assuntos
Humanos , Infecções por HIV/complicações , Sistema Nervoso Central/parasitologia , Sistema Nervoso Central/virologia , Doença de Chagas/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/fisiopatologia , Infecções por HIV/imunologia , Sistema Nervoso Central/imunologia , Doença de Chagas/diagnóstico , Doença de Chagas/fisiopatologia , Doença de Chagas/imunologia , Doença de Chagas/tratamento farmacológico , Diagnóstico DiferencialRESUMO
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 imagemRESUMO
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.