RESUMEN
3-Nitrotriazole-based compounds belonging to various chemical subclasses were found to be very effective against Chagas disease both in vitro and in vivo after a short administration schedule. In this study, five compounds with specific characteristics were selected to be administered for longer periods of time to mice infected with the virulent Trypanosoma cruzi Y strain to further evaluate their effectiveness as antichagasic agents and whether or not potential adverse effects occur. Benznidazole was included for comparison purposes. Complete parasitemia depletion, weight gain, 100% survival, and a lack of myocardial inflammation were observed with four of the compounds and benznidazole administered intraperitoneally at 15 or 20 mg/kg of body weight/day for 40 days. There was a significant reduction in the number of treatment days (number of doses) necessary to induce parasitemia suppression with all four compounds compared to that required with benznidazole. Partial cures were obtained with only one compound tested at 15 mg/kg/day and on the schedule mentioned above but not with benznidazole. Taken together, our data suggest that these compounds demonstrate potent trypanocidal activity comparable to or better than that of the reference drug, benznidazole, when they are administered at the same dose and on the same schedule.
Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Nitroimidazoles/farmacología , Parasitemia/tratamiento farmacológico , Triazoles/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Femenino , Ratones , Triazoles/químicaRESUMEN
Introduction: Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi. Although endemic mainly in Latin America, CD has become a global public health problem due to migration of infected individuals to non-endemic regions. Despite progress made in drug development, preclinical assays for drug discovery are required to accelerate the development of new drugs with reduced side effects, which are much needed for human treatment. Methods: We used a cure model of infected mice treated with Fexinidazole (FZ) to further validate a novel Enzyme Linked Aptamer (ELA) assay that detects parasite biomarkers circulating in the blood of infected animals. Results: The ELA assay showed cure by FZ in ~71% and ~77% of mice infected with the VL-10 and Colombiana strains of T. cruzi, respectively. The ELA assay also revealed superior treatment efficacy of FZ compared to Benznidazole prior to immunosuppression treatment. Discussion: Our study supports the use of ELA assay as an alternative to traditional serology or blood PCR to assess the efficacy of antichagasic drugs during their preclinical phase of development. Further, the combination of high sensitivity and ease of use make this parasite antigen detection assay an attractive new tool to facilitate the development of much needed new therapies for CD.
Asunto(s)
Enfermedad de Chagas , Nitroimidazoles , Trypanosoma cruzi , Humanos , Animales , Ratones , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Resultado del Tratamiento , Pruebas Inmunológicas , Oligonucleótidos/farmacologíaRESUMEN
In recent decades, the oral infection of Trypanosoma cruzi has gathered increased attention due to frequent outbreaks that can lead to more severe clinical signs than those usually found in the areas of vector transmission. This study addresses the main routes of infection using metacyclic trypomastigotes (MT) and blood trypomastigotes (BT). Herein, BALB/c mice were infected with the Colombian (TcI) strain via intraperitoneal (IP), oral, intragastric (IG), ocular (OC) and cutaneous (CT) routes with 106 culture-derived MT or BT. Parasitemia was intermittent and low in animals inoculated with MT, in contrast, high parasitemia levels were found in BT-mice. A tropism for the muscles was observed in oral or IG infection with BT. Differently, the parasite was widely distributed in the tissues of mice infected with MT. However, the intensity of the inflammation infiltrating the tissues was higher in oral or IG infection with BT. Animals inoculated with BT via the IG route had similar serum levels of IFN-γ and smaller IL-10 compared to those infected with MT via the IG route. TNF-α levels were higher in the serum from BT-animals, which could explain the higher intensity of heart inflammation in these animals. Our results suggest that the infective form and the route of infection differentially modulated the outcome of Trypanosoma cruzi mice infection.
Asunto(s)
Enfermedad de Chagas , Enfermedades Transmisibles , Trypanosoma cruzi , Animales , Ratones , Ratones Endogámicos BALB C , Parasitemia/parasitologíaRESUMEN
O estresse é um grave problema de saúde pública e sua gravidade e suscetibilidade se relacionam com uma série de fatores como a idade, a obesidade e a funcionalidade. As mudanças na saúde física, na saúde mental, na vida social e na capacidade cognitiva no envelhecimento predispõem o estresse. Assim, saber manejar o estresse do cotidiano é necessário, principalmente durante a velhice. O presente estudo teve como objetivo avaliar a percepção de estresse, presença de obesidade, funcionalidade e histórico de tabagismo em idosos de uma Universidade Aberta a Pessoa Idosa (UniAPI). Trata-se de um transversal. Foram coletados dados sociodemográficos, aplicado o questionário de percepção de estresse (EPS-10), medidas antropométricas (índice de massa corporal e circunferência de cintura), Escala de Brody e Lawton e histórico de tabagismo de 63 idosos. A comparação entre dois grupos foi realizada com o teste t- Student ou o Teste de Mann-Whitney. Para variáveis categóricas, o teste Qui-quadrado de Pearson e também, regressão linear múltipla ajustados por sexo e idade. A maioria dos idosos eram do sexo feminino (85,7%). Em relação ao estresse, 34% dos idosos apresentaram maior percepção de estresse. O IMC (∆= 3,57 kg/m²) foi maior no grupo com maior percepção de estresse, enquanto o score da escala de Lawton e Brody (∆= 0,47) foi maior no grupo sem percepção. Houve associação entre a presença de percepção de estresse com o IMC (p= 0,031). 100% dos idosos com baixa funcionalidade apresentaram maior percepção de estresse. O IMC (ß= 0,28; p=0,038) e a circunferência de cintura (ß=0,13; p=0,028) tiveram relação direta com o escore de percepção subjetiva de estresse. Em conclusão, a presença de estresse está associada a altos valores de IMC e CC e menor funcionalidade em idosos.
Stress is a serious public health problem and its severity and susceptibility are related to a number of factors such as age, obesity and functionality. Changes in physical health, mental health, social life, and cognitive ability in aging predispose to stress. Thus, knowing how to manage everyday stress is necessary, especially during old age. The present study aimed to evaluate the perception of stress, presence of obesity, functionality and smoking history in elderly people from an Open University for the Elderly (UniAPI). This is a cross-sectional study. We collected sociodemographic data, applied the questionnaire of perceived stress (EPS-10), anthropometric measurements (body mass index and waist circumference), Brody and Lawton Scale and smoking history of 63 elderly. Comparison between two groups was performed with the t-Student test or the Mann-Whitney test. For categorical variables, Pearson's chi-square test and also, multiple linear regression adjusted for gender and age. Most of the elderly were female (85.7%). Regarding stress, 34% of the elderly showed higher perception of stress. The BMI (∆= 3.57 kg/m²) was higher in the group with higher perception of stress, while the Lawton and Brody scale score (∆= 0.47) was higher in the group with no perception. There was an association between the presence of perceived stress and BMI (p= 0.031). 100% of the elderly with low functionality had higher perceived stress. BMI (ß= 0.28; p=0.038) and waist circumference (ß=0.13; p=0.028) had a direct relationship with the score of subjective perception of stress. In conclusion, the presence of stress is associated with high BMI and WC values and lower functionality in the elderly.
El estrés es un grave problema de salud pública y su gravedad y susceptibilidad están relacionadas con una serie de factores como la edad, la obesidad y la funcionalidad. Los cambios en la salud física, la salud mental, la vida social y la capacidad cognitiva en el envejecimiento predisponen al estrés. Por ello, es necesario saber cómo gestionar el estrés cotidiano, especialmente durante la vejez. El presente estudio tuvo como objetivo evaluar la percepción del estrés, la presencia de obesidad, la funcionalidad y los antecedentes de tabaquismo en ancianos de una Universidad Abierta para Ancianos (UniAPI). Se trata de un estudio transversal. Se recogieron datos sociodemográficos, se aplicó el cuestionario de estrés percibido (EPS-10), medidas antropométricas (índice de masa corporal y perímetro de cintura), Escala de Brody y Lawton e historia de tabaquismo a 63 ancianos. La comparación entre dos grupos se realizó con la prueba t-Student o la prueba de Mann-Whitney. Para las variables categóricas, se utilizó la prueba de chi-cuadrado de Pearson y también la regresión lineal múltiple ajustada por sexo y edad. La mayoría de los ancianos eran mujeres (85,7%). En cuanto al estrés, el 34% de los ancianos mostró una mayor percepción de estrés. El IMC (∆= 3,57 kg/m²) fue mayor en el grupo con mayor percepción de estrés, mientras que la puntuación de la escala de Lawton y Brody (∆= 0,47) fue mayor en el grupo sin percepción. Hubo asociación entre la presencia de estrés percibido y el IMC (p= 0,031). El 100% de los ancianos con baja funcionalidad tenían mayor estrés percibido. El IMC (ß= 0,28; p=0,038) y el perímetro de cintura (ß=0,13; p=0,028) tuvieron una relación directa con la puntuación de percepción subjetiva de estrés. En conclusión, la presencia de estrés se asocia a valores elevados de IMC y CC y a una menor funcionalidad en los ancianos.
RESUMEN
Chagas cardiomyopathy remodeling is based on the presence of Trypanosoma cruzi in heart tissue and on the complex inflammatory response leading to a myocardium fibrosis and alterations in conductive and functional heart parameters. This study aims to evaluate Simvastatin on the inflammatory response and heart functionality using dogs infected with Y strain of T. cruzi. Animals were treated daily with Simvastatin (20 mg) for 6 months and submitted to clinical and immunopathological evaluations. Simvastatin reduced heart expression and serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) but not interleukin-10 (IL-10), possibly favoring blood parasitism but reducing inflammation and fibrosis in the left ventricle and right atrium. Simvastatin also ameliorated ejection fraction, diastolic diameter, and mass index of the left ventricle 6 months after infection. This study suggests that more investigation should be performed on the use of statins as a prophylactic therapy against cardiac remodeling because of their effects on modifying immune response and benefiting functional parameters in dogs with T. cruzi-induced ventricular dysfunctions.