RESUMEN
BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. In 30% of cases, after years of infection and in the absence of treatment, the disease progresses from an acute asymptomatic phase to a chronic inflammatory cardiomyopathy, leading to heart failure and death. An inadequate balance in the inflammatory response is involved in the progression of chronic Chagas cardiomyopathy. Current therapeutic strategies cannot prevent or reverse the heart damage caused by the parasite. Aspirin-triggered resolvin D1 (AT-RvD1) is a pro-resolving mediator of inflammation that acts through N-formyl peptide receptor 2 (FPR2). AT-RvD1 participates in the modification of cytokine production, inhibition of leukocyte recruitment and efferocytosis, macrophage switching to a nonphlogistic phenotype, and the promotion of healing, thus restoring organ function. In the present study, AT-RvD1 is proposed as a potential therapeutic agent to regulate the pro-inflammatory state during the early chronic phase of Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 wild-type and FPR2 knock-out mice chronically infected with T. cruzi were treated for 20 days with 5 µg/kg/day AT-RvD1, 30 mg/kg/day benznidazole, or the combination of 5 µg/kg/day AT-RvD1 and 5 mg/kg/day benznidazole. At the end of treatment, changes in immune response, cardiac tissue damage, and parasite load were evaluated. The administration of AT-RvD1 in the early chronic phase of T. cruzi infection regulated the inflammatory response both at the systemic level and in the cardiac tissue, and it reduced cellular infiltrates, cardiomyocyte hypertrophy, fibrosis, and the parasite load in the heart tissue. CONCLUSIONS/SIGNIFICANCE: AT-RvD1 was shown to be an attractive therapeutic due to its regulatory effect on the inflammatory response at the cardiac level and its ability to reduce the parasite load during early chronic T. cruzi infection, thereby preventing the chronic cardiac damage induced by the parasite.
Asunto(s)
Cardiomiopatía Chagásica/tratamiento farmacológico , Ácidos Docosahexaenoicos/administración & dosificación , Animales , Cardiomiopatía Chagásica/genética , Cardiomiopatía Chagásica/inmunología , Cardiomiopatía Chagásica/parasitología , Enfermedad Crónica/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Corazón/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/inmunología , Nitroimidazoles/administración & dosificación , Carga de Parásitos , Receptores de Formil Péptido/genética , Receptores de Formil Péptido/inmunología , Trypanosoma cruzi/fisiologíaRESUMEN
BACKGROUND: The Copenhagen Burnout Inventory (CBI) is a public domain questionnaire measuring the degree of psychological fatigue experienced in three subdimensions of Burnout: personal (PB), work-related (WB), and client-related Burnout (CB). The study aimed to examine the acceptability, reliability and construct validity of the Spanish version of CBI. METHOD: The study population consisted of 479 workers of educational centers, social work centres, healthcare centres and workers within the industry sector. Data was collected in 2009 through a self-administered questionnaire including the three CBI scales, sixteen scales of psychosocial work environment (COPSOQ ISTAS21) and perceived general and mental health and vitality (SF-36). RESULTS: Response rate was 78.7%. The three scales have an inter-item correlation average between 0.42 and 0.60 and a corrected item-total correlation between 0,49 and 0,83. The internal consistency of the three scales had Cronbach's α values of 0.90 for PB, 0.83 for WB and 0.82 for CB. CONCLUSIONS: Burnout was related to both psychosocial work environment and wellbeing measures in the expected direction and intensity. The items of the three scales show good discrimination capacity, good consistency and homogeneity. The three CBI scales have an acceptable internal consistency reliability index, slightly higher in PB. The discrimination capacity of the scales is verified through the discrimination index and the different levels between occupations and activities. These results demonstrate that the Spanish version of the CBI is a reliable and valid instrument for measuring Burnout.