Evaluation of Tpeak–Tend and QT intervals in Chagas’ Disease, Chronic Phase and Normal Electrocardiogram

Introduction: Chagas’ disease lacks elements to predict which carriers will evolve into cardiac form and which will remain in undetermined form. Objective: To evaluate the relationship between electrocardiographic evolution and Tpeak–Tend and QT intervals, both corrected for heart rate, in chagasic patients with normal initial electrocardiogram. Method: Chagasic patients admitted to the institution until 2002 were retrospectively evaluated, and the electrocardiogram was normal at the first consultation. The Tpeak–Tend and QT intervals were measured in milliseconds at the V2 and V5 derivations, with the mean values corrected for heart rate (Bazett). The relationship of these values with the electrocardiographic evolution of the individuals was analyzed, considering the gender, time of evolution and whether they received benznidazole or not. Results: The corrected Tpeak–Tend interval showed no statistical significance among those who maintained or not normal electrocardiogram. The corrected QT interval, the treatment with benznidazole and the time of evolution showed significance for the maintenance of normal electrocardiogram. In the multivariate evaluation, treatment with benznidazole, the QTc interval and the time of evolution were independent variables for the maintenance of normal electrocardiogram. Conclusion: The Tpeak–Tend interval showed no predictor of electrocardiographic evolution. The increased QT interval favored changes

Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination

Abstract INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again

Evaluation of Parasiticide Treatment with Benznidazol in the Electrocardiographic, Clinical, and Serological Evolution of Chagas Disease.

INTRODUCTION:Chagas disease is one of the most important endemic parasitic diseases in Latin America. In its chronic phase, progression to cardiomyopathy has high morbidity and mortality. The persistence of a normal electrocardiogram (ECG) provides a similar prognosis to that of a non-diseased population. Benznidazole (BNZ) is the only drug with trypanocidal action available in Brazil. MATERIALS/METHODS/RESULTS:A group of 310 patients with chronic Chagas disease who had normal ECGs at the first medical visit performed before 2002 were included. There were 263 patients treated with BNZ and 47 untreated. The follow-up period was 19.59 years. Univariate analyses showed that those treated were younger and predominantly male. As many as 79.08% of those treated and 46.81% of those untreated continued with normal electrocardiograms (p <0.0001). The occurrence of electrocardiographic abnormalities and relevant clinical events (heart failure, stroke, total mortality, and cardiovascular death) was less prevalent in treated patients (p <0.001, p: 0.022, p: 0.047 respectively). In multivariate analyses, the parasiticide treatment was an independent variable for persistence of a normal ECG pattern, which was an independent variable in the prevention of significant clinical events. The immunofluorescence titers decreased with the parasitological treatment. However, the small number of tests in untreated patients did not allow the correlation of the decrease of these titers with electrocardiographic alterations. CONCLUSION:These data suggest that treatment with benznidazole prevents the occurrence of electrocardiographic alterations. On the other hand, patients who develop ECG abnormalities present with more significant clinical events

Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination

<div><p>Abstract INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.</p></div

Baseline characteristics of patients found and not found.

<p>Baseline characteristics of patients found and not found.</p

Characteristics of the untreated and treated with BZ groups.

<p>Characteristics of the untreated and treated with BZ groups.</p

Logistic regression model.

<p>Dependent variable: normal ECG maintenance and independent variables: treatment with BZ, follow-up, male, Caucasian and age in years.</p

Patients untreated and treated with BZ and events occurrence.

<p>Patients untreated and treated with BZ and events occurrence.</p

Efecto del entrenamiento físico en alteraciones inducidas por el envejecimiento en el músculo papilar de la rata

FUNDAMENTO: Os efeitos do envelhecimento no músculo papilar têm sido amplamente demonstrados, mas não há dados disponíveis sobre os efeitos do exercício nas alterações relacionadas à idade. OBJETIVO: Analisar os efeitos do envelhecimento nas propriedades morfológicas e quantitativas do músculo papilar e investigar se um programa contínuo de exercícios moderados pode exercer um efeito protetor contra as conseqüências do envelhecimento. MÉTODOS: Microscopia eletrônica foi utilizada para estudar a densidade dos miócitos, capilares e tecido conectivo e área transversal dos miócitos do músculo papilar no ventrículo esquerdo de ratos Wistar de 6 e 13 meses, não-treinados e submetidos a exercícios. RESULTADOS: Como esperado, a densidade de volume dos miócitos diminui significantemente (p<0,05) com a idade. A densidade de comprimento dos capilares também diminui com a idade, mas não de forma significante. A fração de volume intersticial do tecido do músculo capilar aumenta significantemente com a idade (P<0,05). O número de perfis de miócitos mostrou uma redução de 20% que foi acompanhada de hipertrofia dos miócitos no envelhecimento (P<0,05). Animais submetidos a uma sessão diária de 60 minutos, 5 dias/semana a 1,8 km.h-1 de corrida moderada em esteira ergométrica durante 28 semanas mostraram uma reversão de todos os efeitos do envelhecimento observados no músculo papilar. CONCLUSÃO: O presente estudo apóia o conceito de que treinamento físico de longo prazo impede as mudanças deletérias relacionadas à idade no músculo capilar.BACKGROUND: The effects of aging on papillary muscle have been widely demonstrated, but no data on the effects of exercise on the age-related changes are available. OBJECTIVE: To analyze the effects of aging on the morphological and quantitative properties of papillary muscle and investigate whether a long-term moderate exercise program would exert a protective effect against the effects of aging. METHODS: We used electron microscopy to study the density of myocytes, capillaries and connective tissue and the cross-sectional area of myocytes of the papillary muscle of the left ventricle of 6- and 13-month-old untrained and exercised Wistar rats. RESULTS: As expected, the volume density of myocytes declined significantly (p<0.05) with aging. The length density of myocardial capillaries also declined with aging, but not significantly. The interstitial volume fraction of the papillary muscle tissue increased significantly (P<0.05) with age. The number of myocyte profiles showed a reduction of 20% that was accompanied by myocyte hypertrophy in the aged rats (P<0.05). Animals submitted to a 60-minute daily session,, 5 days/wk at 1.8 km.h-1 of moderate running on a treadmill for 28 weeks showed a reversion of all the observed aging effects on papillary muscle. CONCLUSION: The present study supports the concept that long-term exercise training restrains the aging-related deleterious changes in the papillary muscle.FUNDAMENTO: Los efectos del envejecimiento en el músculo papilar han sido demostrados de modo amplio, pero no hay datos disponibles sobre los efectos del ejercicio en las alteraciones relacionadas a la edad. OBJETIVO: Analizar los efectos del envejecimiento en las propiedades morfológicas y cuantitativas del músculo papilar e investigar si un programa continuo de ejercicios moderados puede ejercer un efecto protector contra las consecuencias del envejecimiento. MÉTODOS: Se utilizó microscopia electrónica para estudiar la densidad de los miocitos, capilares y tejido conectivo, así como el área transversal de los miocitos del músculo papilar en el ventrículo izquierdo de ratas Wistar de 6 y 13 meses, no entrenadas y sometidas a ejercicios. RESULTADOS: Como se esperaba, la densidad de volumen de los miocitos disminuye significantemente (p<0,05) con el avance de la edad. La densidad de longitud de los capilares también disminuye con la edad, pero no de forma significante. La fracción de volumen intersticial del tejido del músculo capilar aumenta significantemente con el avance de la edad (P<0,05). El número de perfiles de miocitos mostró una reducción del 20%, seguida de su hipertrofia en el envejecimiento (P<0,05). Sometidos a una sesión diaria de 60 minutos, 5 días/semana a 1,8 km.h-1 de corrida moderada en estera ergométrica durante 28 semanas, los animales mostraron una reversión de todos los efectos del envejecimiento observados en el músculo papilar. CONCLUSIÓN: El presente estudio apoya el concepto de que entrenamiento físico de largo plazo impide los cambios letales en el músculo capilar relacionados a la edad

Exploring the Evolutionary Origin and Biological Role of the <em>Trypanosoma cruzi</em> Ecotin-Like Molecule in Chagas’ Disease

Enzymes called proteases play important roles in the physiology of all living organisms and in the interaction of a parasite/symbiont with its host. Different types of peptidases act on specific substrates and are regulated by specific inhibitors. Ecotins, described firstly in Eschericchia coli, are inhibitors of serine peptidases (ISP) from S1A family including trypsin, chymotrypsin, neutrophil elastase, and cathepsin G. Ecotin-like inhibitors are present in parasites from Trypanosomatidae family, including Trypanosoma cruzi, the causative agent of Chagas’ disease. This chapter explores the evolutive origin of the T. cruzi TcISP2 and its possible interactions with proteins of the human immune system and in Chagas’ disease. The phylogenetic relationship of TcISP2 with trypanosomatids ISPs, comparative loci analysis among trypanosomatids, and the occurrence of bacteria endosymbionts in the group strongly suggest horizontal transfer as the main origin mechanism for trypanosomatids ISPs, followed by duplication events and losses that could explain its current genomic pattern. The relationship of TcISP2 with the vertebrate host immune system can be inferred by its antigenicity in Chaga’s disease murine model, presenting high antibody titer after 60 days post-infection, which could indicate the inhibition of TcISP2 activity associated with chronic phase of the Chaga’s disease