RESUMEN
In spite of the fact that hypertension stand out as the main vascular risk factor for developing dementia, it is essential to acknowledge the presence of other risk factors, both vascular and non-vascular that contribute to increase this risk. This study stratified the dementia risk using CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) dementia risk score in a sample of 1279 hypertensive patients from the Heart-Brain Study in Argentina and to observed the association between the risk factors include in the CAIDE score and the current cognitive status. The average age of the sample was 60.2 ± 13.5 years (71% female) and the average years of education was 9.9 ± 5.1 years. To assess the current cognitive status, we used the Mini-mental test (MMSE), the clock drawing test (CDT) and Mini-Boston test. According to CAIDE score ( ≥9 points) the risk of dementia was 40.4% in the total sample and 28.1% in the middle-life hypertensive patients (between 47 to 53 years). An inverse association was observed between CAIDE score and the results of current cognitive tests (MMSE = R2 0.9128, p < 0.0001; CDT = R2 0.9215, p < 0.0001 y Mini-Boston= R2 0.829, p < 0.0001). The CAIDE score can predict the risk of dementia in hypertensive patients and its result was associated with the current cognitive status (result of cognitive tests).
Asunto(s)
Cognición , Demencia , Hipertensión , Humanos , Femenino , Hipertensión/complicaciones , Hipertensión/epidemiología , Demencia/epidemiología , Demencia/etiología , Masculino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Argentina/epidemiología , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: To estimate the prevalence of mood and anxiety disorders among adults seeking care in primary healthcare centers in Cordoba city, Argentina. METHODS: Cross-sectional analysis of a random sample of adults 18-69 years of age seeking care for general health problems in public (i.e., government-funded) primary healthcare centers in Cordoba city, Argentina in 2010-2011. Mood and anxiety disorders were assessed in the participants' lifetime, and in the last 12 months and 30 days using the World Mental Health Composite International Diagnostic Interview 3.0, and defined following the International Classification of Diseases, tenth revision. RESULTS: Overall, 1,067 participants were included in the current analysis [mean age 35.6 (SD 13.2) years, 83.7% female]. The lifetime, 12-month and 30-day prevalence of any mood or anxiety disorder was 40.4% [95% confidence interval (95%CI) 37.4-43.4%], 20.1% (17.8-22.7%) and 7.8% (6.2-9.6%), respectively. The prevalence of anxiety disorders was higher compared to mood disorders when assessed in the participants' lifetime [29.7% (95%CI 27.0-32.5%) versus 19.3% (17.0-21.8%)], and in the last 12 months [14.9% (12.8-17.2%) versus 8.7% (7.1-10.6%)] and 30 days [5.8% (4.5-7.4%) versus 2.3% (1.5-3.4%)]. Age and marital status-adjusted odds ratios for any mood or anxiety disorder in the participants' lifetime and in the last 12 months and 30 days comparing women versus men were 1.19 (95%CI 0.85-1.67), 1.70 (1.07-2.69), and 2.26 (1.02-5.00), respectively. CONCLUSION: The prevalence of mood and anxiety disorders is high among adults seeking care in primary healthcare centers in Cordoba city, particularly among women. Integration of primary and mental health services is warranted.
Asunto(s)
Trastornos Mentales/epidemiología , Salud Mental/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Adulto , Anciano , Argentina/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Salud Mental/tendencias , Persona de Mediana Edad , Prevalencia , Atención Primaria de Salud/tendencias , Salud Pública/estadística & datos numéricos , Salud Pública/tendencias , Factores Socioeconómicos , Adulto JovenRESUMEN
UNLABELLED: The severe and chronic mental illnesses such as schizophrenia are associated with very complex problems that are not confined to the symptoms but also affect psychosocial functioning and community integration. OBJECTIVE: To evaluate the reliability (in terms of internal consistency) of the WHODAS 2.0 for analyzing the psychosocial functioning of people with schizophrenia living in the community and using mental health services, and report the WHODAS 2.0 results from the same sample. METHODS: The sample comprised 100 users diagnosed with schizophrenia (F20 to F29 of ICD 10) living in the community and in contact with mental health services in Córdoba, Buenos Aires and San Luis in Argentina. Interviewers were trained in the use of the WHODAS 2.0. RESULTS: For the overall internal consistency of the WHODAS 2.0: Cronbach's alpha = 0.78. WHODAS 2.0 results for these service users were: Domain 1, 57% none, 19.4% mild, 20.4% moderate, 3.2% severe. Domain 2, 60.2% none, 18.3% mild, 17.2% moderate, 3.2% severe. Domain 3, 54.9% none, 23.7% mild, 19.4% moderate, 2.2% severe. Domain 4, 74.2% none, 18.3% mild, 6.5% moderate, 1.1% severe. Domain 5, 82.8% none, 1.8% mild, 4.3% moderate, 1.1% severe. Domain 6, 81.7% none, 15.1% mild, 3.2% moderate. CONCLUSIONS: WHODAS 2.0 showed high internal consistency in this population. Most of the service users had no disability or mild disability in all 6 domains. A substantial minority had moderate disability in some domains (D1, D3). In all domains, <5% had severe disability.
Asunto(s)
Evaluación de la Discapacidad , Escala del Estado Mental/normas , Psicología del Esquizofrénico , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud , Masculino , Servicios de Salud Mental , Psicometría/normas , Calidad de Vida , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto JovenRESUMEN
UNLABELLED: The association between chronic pain and mental disorders is a determining factor of the disease evolution and requires a comprehensive approach in patients. OBJECTIVE: evaluate the prevalence of mental disorders in patients with chronic pain who use the service of Neurology at the National Clinical Hospital, Cordoba, Argentina. METHODOLOGY: the study included patients with chronic pain who used the Neurology service, National Clinical Hospital in Cordoba, Argentina, selected from a validated form that contains the appropriate clinical criteria. Mental disorders were evaluated in a sample of 351 patients through the CIDI 3.0. The interviewers were properly trained to implement it. Data were analyzed using InfoStat® statistical software. RESULTS: The mean age of the sample was 41.94±2.02 years, ranging from 20 to 65, 88.32% being women. It showed that 50.98% of the consultants for chronic pain had an episode of mental disorders throughout their life. Thus, the lifetime prevalence for affective disorders was 29.4% and neurotic disorders, stress related disorders and somatoform disorders was 41.2%. CONCLUSION: The results contributed to identify the background frequency and characteristics of mental disorders in patients presenting with chronic pain in a service of Neurology, requiring the need to implement a comprehensive clinical intervention, and to continue the research to assess concurrent comorbidity of both conditions.
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Dolor Crónico/epidemiología , Trastornos Mentales/epidemiología , Adulto , Anciano , Argentina/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurología , Prevalencia , Distribución por Sexo , Adulto JovenRESUMEN
UNLABELLED: Many individuals with behavioral and mental health disorders do not receive care in specialized mental health services. These individuals could potentially be identified and managed in the primary healthcare level. OBJECTIVE: To analyze the coverage gap on mental health disorders in the primary healthcare level of Córdoba city, Argentina. METHODOLOGY: Stratified multistage random sample of individuals 19 to 69 years of age seeking care in primary healthcare centers of the public health system in Córdoba city. Presence of behavioral and mental health disorder and receiving healthcare through mental health services were assesed using CIDI 3.0. Data were analyzed using descriptive statistics. RESULTS: A total of 1,067 individuals were included in the present analysis. Overall, 20.15% of individuals included in the analysis had behavioral and mental health disorders during the last year, of whom 77.33% did not receive care through mental health services. DISCUSSION AND CONCLUSION: The proportion of individuals with behavioral and mental health disorders and of those who did not receive care through mental health services are similar to those observed in other Latin American countries, but higher than those reported in Europe. This communication gives preliminary results about the coverage gap on mental health disorders present in the primary healthcare level in Cordoba city. These individuals may benefit from interventions aimed to identify and manage those with mental health disorders in the primary healthcare level.
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Trastornos Mentales/epidemiología , Servicios de Salud Mental/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Adulto , Anciano , Argentina/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Distribución por Sexo , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTION: The General Health Questionnaire (GHQ-12) is a commonly used instrument to screen for psychiatric distress. However, the psychometric properties and reliability of the GHQ-12 in Argentina and, more specifically, in the city of Cordoba, have not previously been studied. OBJECTIVE: To assess the psychometric properties and reliability of GHQ-12 in adult consultants of primary care in Cordoba, Argentina. METHODS: Using probabilistic sampling in primary care centers in the city of Cordoba, a cross-sectional study was conducted. The Spanish version of the GHQ-12 was administered. The psychometric properties, including internal consistency and factor structure, for the Spanish version of the GHQ-12 were measured. RESULTS: 854 primary care consultants were included in the study. The questionnaire had high internal consistency, with a Cronbach's alpha of 0.80. An exploratory factor analysis suggested a two-factor model, similar to what has been reported for the original questionnaire. CONCLUSIONS: The GHQ-12 showed good psychometric properties and reliability in the studied population.
Asunto(s)
Atención Primaria de Salud/estadística & datos numéricos , Estrés Psicológico/diagnóstico , Encuestas y Cuestionarios/normas , Adulto , Distribución por Edad , Anciano , Argentina , Femenino , Humanos , Lenguaje , Masculino , Estado Civil , Persona de Mediana Edad , Psicometría , Valores de Referencia , Reproducibilidad de los Resultados , Distribución por Sexo , Estadísticas no Paramétricas , Adulto JovenRESUMEN
INTRODUCTION: Academic performance is a product of the complex environment that surrounds the student, shaped by aspects such as intensity of study, motivation and context of relationships, which affect the academic achievement of individuals. There may be other psychological or emotional factors, such as anxiety, level of psychological well-being, and behavior strategies for effective adaptation to concrete environment demands and their associated emotional stress. OBJECTIVES: This research study aims at determining the level of psychological well-being and coping strategies in students of the Basic Common Cycle of studies leading to an MD degree in the School of Medicine of the National University of Córdoba, Argentina. METHODS AND MATERIALS: This is an observational study based on a "Questionnaire on determiners of academic performance", that was answered by 374 students. Data was processed using statistical bivariate analysis (p< 0.05) and multiple correspondence factorial analysis. RESULTS: Students with "VG/G (Very Good/Good) performance" show high levels of satisfaction and well-being use direct coping strategies which lead them to "cope with problematic situations" by means of "problem solving". Students with "R/I (Regular/Insufficient) academic performance" declare "dissatisfaction with most aspects of their personalities", feel unable to give a satisfactory response to environment demands, and assume "avoidance behaviors" as coping strategies. CONCLUSIONS: Student academic performance is associated with psychological well-being, feeling of satisfaction with achievements, and coping with stressful situations.
Introducción: El rendimiento académico es producto del complejo mundo que envuelve al estudiante, determinado por aspectos cotidianos (intensidad de estudio, motivación y medio relacional) que afectan el desempeño académico de los individuos. Otros factores pueden ser psicológicos o emocionales tales como la ansiedad, el grado de bienestar psicológico y las estrategias conductuales tendientes a lograr una adaptación efectiva a las demandas concretas del ambiente y al estrés emocional asociado. Objetivos: En esta investigación se propuso identificar el nivel de bienestar psicológico y las estrategias de afrontamiento en los estudiantes del Ciclo Básico de la Carrera de Medicina y analizar la relación entre bienestar, afrontamiento y rendimiento académico. Material y método: Es un estudio observacional el cual se trabajó a partir del "Cuestionario Determinantes relacionados con el rendimiento académico" implementado a 374 alumnos. El análisis de los datos se efectuó a través del procesamiento estadístico con análisis bivariado (p<0,05) y análisis factorial de correspondencia múltiple. Resultados: Los alumnos con "Rendimiento MB/B" presentan altos niveles de satisfacción y bienestar utilizando un afrontamiento directo que contribuye a "enfrentar las situaciones que preocupan" mediante la "solución de problemas". En tanto que los alumnos con "Rendimiento R/I" perciben "disgusto con la mayoría de los aspectos de su personalidad" sintiéndose impedidos para responder satisfactoriamente a las demandas del ambiente, asumiendo "comportamientos de evitación" como forma de afrontamiento. Conclusiones: El rendimiento académico de los estudiantes se asocia con la presencia de bienestar psicológico, satisfacción con respecto a los logros alcanzados y el afrontamiento de situaciones estresoras.
Asunto(s)
Logro , Adaptación Psicológica , Satisfacción Personal , Estrés Psicológico/psicología , Estudiantes de Medicina/psicología , Adolescente , Adulto , Argentina , Estudios Transversales , Femenino , Humanos , Masculino , Motivación , Autoimagen , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION: Academic performance is a product of the complex environment that surrounds the student, shaped by aspects such as intensity of study, motivation and context of relationships, which affect the academic achievement of individuals. There may be other psychological or emotional factors, such as anxiety, level of psychological well-being, and behavior strategies for effective adaptation to concrete environment demands and their associated emotional stress. OBJECTIVES: This research study aims at determining the level of psychological well-being and coping strategies in students of the Basic Common Cycle of studies leading to an MD degree in the School of Medicine of the National University of Córdoba, Argentina. METHODS AND MATERIALS: This is an observational study based on a "Questionnaire on determiners of academic performance", that was answered by 374 students. Data was processed using statistical bivariate analysis (p< 0.05) and multiple correspondence factorial analysis. RESULTS: Students with "VG/G (Very Good/Good) performance" show high levels of satisfaction and well-being use direct coping strategies which lead them to "cope with problematic situations" by means of "problem solving". Students with "R/I (Regular/Insufficient) academic performance" declare "dissatisfaction with most aspects of their personalities", feel unable to give a satisfactory response to environment demands, and assume "avoidance behaviors" as coping strategies. CONCLUSIONS: Student academic performance is associated with psychological well-being, feeling of satisfaction with achievements, and coping with stressful situations.
Asunto(s)
Logro , Adaptación Psicológica , Satisfacción Personal , Estrés Psicológico/psicología , Estudiantes de Medicina/psicología , Adolescente , Adulto , Argentina , Estudios Transversales , Femenino , Humanos , Masculino , Motivación , Encuestas y Cuestionarios , Autoimagen , Adulto JovenRESUMEN
INTRODUCTION: Academic performance is a product of the complex environment that surrounds the student, shaped by aspects such as intensity of study, motivation and context of relationships, which affect the academic achievement of individuals. There may be other psychological or emotional factors, such as anxiety, level of psychological well-being, and behavior strategies for effective adaptation to concrete environment demands and their associated emotional stress. OBJECTIVES: This research study aims at determining the level of psychological well-being and coping strategies in students of the Basic Common Cycle of studies leading to an MD degree in the School of Medicine of the National University of Córdoba, Argentina. METHODS AND MATERIALS: This is an observational study based on a "Questionnaire on determiners of academic performance", that was answered by 374 students. Data was processed using statistical bivariate analysis (p< 0.05) and multiple correspondence factorial analysis. RESULTS: Students with "VG/G (Very Good/Good) performance" show high levels of satisfaction and well-being use direct coping strategies which lead them to "cope with problematic situations" by means of "problem solving". Students with "R/I (Regular/Insufficient) academic performance" declare "dissatisfaction with most aspects of their personalities", feel unable to give a satisfactory response to environment demands, and assume "avoidance behaviors" as coping strategies. CONCLUSIONS: Student academic performance is associated with psychological well-being, feeling of satisfaction with achievements, and coping with stressful situations.
Asunto(s)
Adaptación Psicológica , Estrés Psicológico/psicología , Estudiantes de Medicina/psicología , Logro , Satisfacción Personal , Adolescente , Adulto , Adulto Joven , Argentina , Autoimagen , Estudios Transversales , Femenino , Humanos , Encuestas y Cuestionarios , Masculino , MotivaciónRESUMEN
We have previously shown that clomipramine and allopurinol used separately are effective in preventing chronic chagasic cardiomyopathy. The aim of the present study was to evaluate the effect of the association of clomipramine (Clo--5 mg/kg/day/90 days) and allopurinol (Allo--5, 10, or 15 mg/kg/day/90 days) for the treatment of experimental Chagas disease in the acute stage. Treatment effectiveness was evaluated through parasitemia, survival, electrocardiography, serology, and cardiac histopathology. Groups treated showed no electrocardiographic abnormalities, in contrast to those untreated which presented 25% of mice with conduction alterations. The myocardium of treated mice (Clo, Allo10+Clo, and Allo15+Clo) presented no structural alterations. Cardiac b-receptor affinity was preserved in mice treated with Clo or Clo+Allo at the different doses; receptor density of the Clo and Allo15+Clo groups did not differ from the non-infected group. Anti-cruzipain antibody levels were similar in treated and untreated groups. Survival was significantly increased in the treated groups (p < 0.05), with Clo and all the Clo+Allo groups presenting the highest rates. These results show that the association of clomipramine + allopurinol is effective for Chagas disease treatment and has the same effect as clomipramine alone.
Asunto(s)
Alopurinol/administración & dosificación , Antiprotozoarios/administración & dosificación , Enfermedad de Chagas/tratamiento farmacológico , Clomipramina/administración & dosificación , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Cisteína Endopeptidasas/inmunología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Electrocardiografía , Masculino , Ratones , Miocardio/patología , Parasitemia/tratamiento farmacológico , Proteínas Protozoarias , Análisis de Supervivencia , Resultado del Tratamiento , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/aislamiento & purificaciónRESUMEN
The chronic indeterminate form of Trypanosoma cruzi infection could be the key to knowing which patients will develop chagasic myocardiopathy. Infected mice present a period in which cardiac functional and structural alterations are different from those described for acute or chronic phases. We studied some components of the cardiac ß-adrenergic system in mouse hearts infected with T. cruzi Tulahuen strain or SGO-Z12 isolate during the chronic indeterminate phase of infection. We determined: (i) the primary messenger (epinephrine and norepinephrine) levels in plasma by reverse-phase-HPLC; (ii) the cardiac ß-adrenergic receptors' (ß-AR) density and affinity by binding with tritiated dihidroalprenolol and by immunofluorescence; (iii) the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the phosphorylation of the proteins involved in cardiac contraction; (iv) the cardiac contractility and functional studies of the ß-ARs as a response to the ligand binding to the receptor; and (v) the left ventricular ejection fraction as a measure of in vivo cardiac function. Plasma catecholamines levels remained similar to those found in uninfected controls. The ß-ARs' affinity decreased in both infected groups compared with the uninfected group (P<0.05) while the receptors' density increased only in the SGO-Z12 group (P<0.01). Cyclic AMP levels were higher in both infected groups (P<0.01) relative to controls, and were higher in SGO-Z12-infected mice compared with those infected with the Tulahuen strain. However, the basal contractile force remained unchanged and the response to catecholamines only increased in the Tulahuen group (P<0.05). The left ventricular ejection fraction, on the other hand, was diminished in SGO-Z12-infected mice. Heterogeneity between T. cruzi strains determine, in the chronic indeterminate form, alterations in the signaling pathways of the ß-adrenergic system at different levels: (i) between catecholamines and the ß(1)-receptors; (ii) between the receptors' activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.
Asunto(s)
Cardiomiopatía Chagásica/metabolismo , Receptores Adrenérgicos beta/metabolismo , Trypanosoma cruzi/fisiología , Animales , Cardiomiopatía Chagásica/parasitología , Cardiomiopatía Chagásica/fisiopatología , AMP Cíclico/metabolismo , Electrocardiografía , Epinefrina/metabolismo , Corazón/parasitología , Corazón/fisiopatología , Humanos , Ratones , Contracción Miocárdica , Miocardio/metabolismo , Norepinefrina/metabolismo , Transducción de SeñalRESUMEN
There is a real need for new and less toxic drugs for the treatment of Chagas disease, as nifurtimox and benznidazole are effective but toxic and provoke unpleasant side effects, especially in adult patients. Allopurinol, commonly used to treat the hiperuricemia, is also used by the Trypanosoma cruzi's hypoxantine guanine fosforyltransferase as an alternative substrate incorporating it into the parasite's ribonucleic acid, provoking the death of the parasite. However, the results of using allopurinol as chemotherapy for Chagas disease are not clear. For that, we investigated the evolution of the T. cruzi infection in mice treated with allopurinol (5, 10 or 15 mg/kg for 90 days) obtaining a reduction in the parasitaemia (p<0.05), no electrocardiographic alterations (p<0.05) and a conserved myocardial and cardiac beta-receptors' affinity values with the highest dose of the drug, compared to those of the uninfected mice. Cruzipain immunoglobulin G levels remained high in all the groups as well as the survival (70%, 90 days post-infection). Allopurinol prevented the acute phase evolving into the chronic cardiac disease.
Asunto(s)
Alopurinol/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Trypanosoma cruzi/efectos de los fármacos , Alopurinol/administración & dosificación , Animales , Anticuerpos Antiprotozoarios/sangre , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/fisiopatología , Cisteína Endopeptidasas/inmunología , Electrocardiografía , Masculino , Ratones , Miocardio/patología , Parasitemia , Proteínas Protozoarias , Análisis de Supervivencia , Trypanosoma cruzi/crecimiento & desarrolloRESUMEN
Chronic Chagas' disease represents the result of the interaction between the host and the parasite, producing different clinical features: from a mild disease to a severe heart failure. In the present investigation, we analyzed whether Trypanosoma cruzi strain and/or reinfections in the acute stage, determine changes in the chronic phase (135 days postinfection, d.p.i) that could explain the diverse evolution of cardiac lesions. After infection of albino Swiss mice (n = 170) with 50 blood trypomastigote of the T. cruzi, strain Tulahuen (n = 80) and the isolate SGO-Z12 (n = 90), respectively, and reinfections at 10 and 20 d.p.i. Parasitemia, survival, electrocardiography, affinity and density of cardiac beta-receptors and histopathology of the heart were studied. Parasitemias in reinfected mice were significantly higher than those in single-infected mice. Survival of SGO-Z12-infected group was significantly higher than the other groups (p < 0.01). All Tulahuen-reinfected mice and 55-67% of the infected and SGO-Z12-reinfected groups presented some electrocardiographic abnormality (p < 0.01). Hearts from single-infected mice presented fibber disorganization and necrosis; reinfected groups also exhibited fibber fragmentation and a diminished affinity and a higher beta-adrenergic receptors' density than the other groups (p < 0.05). Therefore, parasite strain and reinfections determine different cardiac damage, and either (or both) of these factors are involved in the severity of the clinical picture and the prognosis of the chronic cardiac disease.
Asunto(s)
Cardiomiopatía Chagásica/parasitología , Trypanosoma cruzi/clasificación , Trypanosoma cruzi/fisiología , Animales , Femenino , Ratones , Parasitemia , Pronóstico , Recurrencia , Factores de TiempoRESUMEN
Mice infected with Trypanosoma cruzi Tulahuen strain or SGO-Z12 isolate were treated at 180 days post infection (p.i.) (i.e. chronic phase) with benznidazole (for 30 days) or thioridazine (for 12 days). Both drugs produced a decrease in electrocardiographic alterations, fewer modifications in the affinity and density of cardiac beta-receptors, and few isolated areas of fibrosis in the heart, whereas untreated mice presented areas of necrosis and fibre fragmentation 350 days p.i. (P<0.01). Survival in treated mice was 100% for benznidazole and 88% for thioridazine, independent of the parasite strain; survival for untreated mice was 30% and 40% for Tulahuen strain and SGO-Z12 isolate, respectively (P<0.01). No cardiotoxic effects of thioridazine were detected at the dose and treatment schedule used. These results show the benefit of treatment in the chronic phase of Chagas disease and that thioridazine should be considered as a promising agent for the treatment of Chagas disease.
Asunto(s)
Cardiomiopatía Chagásica/tratamiento farmacológico , Enfermedad de Chagas/tratamiento farmacológico , Nitroimidazoles/uso terapéutico , Tioridazina/uso terapéutico , Tripanocidas/uso terapéutico , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Electrocardiografía , Ratones , Nitroimidazoles/farmacología , Tioridazina/farmacología , Tripanocidas/farmacologíaRESUMEN
BACKGROUND: It has been demonstrated that the beta-adrenergic signal transduction system is altered somewhere along its pathway in Trypanosoma cruzi infected hearts and we think that these alterations would differ according to the infection phase and the parasite strain. Their study would be important for the understanding of the disease's pathophysiology. METHODS: In the present work we studied important components of this system in mice hearts infected with T. cruzi, Tulahuen strain and with SGO-Z12 isolate, obtained from a patient of an endemic area, in the acute phase of the infection, determining: the plasma catecholamines levels, the beta-receptors density and affinity as well as their function, the cardiac concentration of cAMP and the cardiac contractility as the physiologic response to the initial stimulus. RESULTS: Plasma catecholamines levels were diminished in both infected groups when compared to the uninfected one (P < 0.01). The receptor's affinity was also diminished (P < 0.05) while their density was augmented only in the SGO-Z12 infected one (P < 0.01). The cAMP levels were higher in both infected groups (P < 0.01), the basal contractile force however increased only in the Tulahuen infected one (P < 0.01) while the response to catecholamines remained unchanged. The hearts infected with the SGO Z12 isolate presented an inferior response to epinephrine (P < 0.05) than the ventricles infected with the Tulahuen strain. CONCLUSIONS: This model represents an important approach to understand the biochemical, physiological and molecular changes in the cardiac beta-adrenergic signalling that clearly begin in the acute phase of Chagas' disease and reveal a clear differentiation in the alterations produced by different parasite strains.
Asunto(s)
Catecolaminas/sangre , Cardiomiopatía Chagásica/sangre , Epinefrina/sangre , Norepinefrina/sangre , Receptores Adrenérgicos beta/análisis , Animales , AMP Cíclico/análisis , Corazón/fisiopatología , Humanos , Ratones , Miocardio/química , Receptores Adrenérgicos beta/fisiologíaRESUMEN
In Chagas disease serious cardiac dysfunction can appear. We specifically studied the cardiac function by evaluating: ventricle contractile force and norepinephrine response, affinity and density of beta-adrenergic receptors, dynamic properties of myocardial membranes, and electrocardiography. Albino swiss mice (n = 250) were infected with 55 trypomastigotes, Tulahuen strain and studied at 35, 75, and 180 days post-infection, that correspond to the acute, indeterminate, and chronic phase respectively. Cardiac beta-adrenergic receptors' affinity, myocardial contractility, and norepinephrine response progressively decreased from the acute to the chronic phase of the disease (p < 0.01). The density (expressed as fmol/mg.prot) of the receptors was similar to non-infected mice (71.96 ± 0.36) in both the acute (78.24 ± 1.67) and indeterminate phases (77.28 ± 0.91), but lower in the chronic disease (53.32 ± 0.71). Electrocardiographic abnormalities began in the acute phase and were found in 65 percent of the infected-mice during the indeterminate and chronic phases. Membrane contents of triglycerides, cholesterol, and anisotropy were similar in all groups. A quadratic correlation between the affinity to beta-adrenergic receptors and cardiac contractile force was obtained. In conclusion the changes in cardiac beta-adrenergic receptors suggests a correlation between the modified beta-adrenergic receptors affinity and the cardiac contractile force.
Asunto(s)
Animales , Ratones , Enfermedad de Chagas , Fluidez de la Membrana , Contracción Miocárdica , Norepinefrina , Receptores Adrenérgicos beta , Trypanosoma cruzi , Enfermedad Aguda , Cardiomiopatía Chagásica , Enfermedad Crónica , Modelos Animales de Enfermedad , ElectrocardiografíaRESUMEN
In Chagas disease serious cardiac dysfunction can appear. We specifically studied the cardiac function by evaluating: ventricle contractile force and norepinephrine response, affinity and density of beta-adrenergic receptors, dynamic properties of myocardial membranes, and electrocardiography. Albino swiss mice (n = 250) were infected with 55 trypomastigotes, Tulahuen strain and studied at 35, 75, and 180 days post-infection, that correspond to the acute, indeterminate, and chronic phase respectively. Cardiac beta-adrenergic receptors' affinity, myocardial contractility, and norepinephrine response progressively decreased from the acute to the chronic phase of the disease (p < 0.01). The density (expressed as fmol/mg.prot) of the receptors was similar to non-infected mice (71.96 +/- 0.36) in both the acute (78.24 +/- 1.67) and indeterminate phases (77.28 +/- 0.91), but lower in the chronic disease (53.32 +/- 0.71). Electrocardiographic abnormalities began in the acute phase and were found in 65% of the infected-mice during the indeterminate and chronic phases. Membrane contents of triglycerides, cholesterol, and anisotropy were similar in all groups. A quadratic correlation between the affinity to beta-adrenergic receptors and cardiac contractile force was obtained. In conclusion the changes in cardiac beta-adrenergic receptors suggests a correlation between the modified beta-adrenergic receptors affinity and the cardiac contractile force.
Asunto(s)
Enfermedad de Chagas/fisiopatología , Fluidez de la Membrana , Contracción Miocárdica , Norepinefrina/metabolismo , Receptores Adrenérgicos beta/metabolismo , Trypanosoma cruzi/patogenicidad , Enfermedad Aguda , Animales , Cardiomiopatía Chagásica/metabolismo , Cardiomiopatía Chagásica/fisiopatología , Enfermedad de Chagas/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad , Electrocardiografía , Masculino , RatonesRESUMEN
Cardiac beta-adrenergic receptors' function was studied in the acute phase of Chagas' disease in mice reinfected with Trypanosoma cruzi Tulahuen strain (Tul) and with parasites isolated from an infected patient (SGO-Z12). Genetic characterization of SGO-Z12 isolates demonstrated that it belongs to the zimodeme Z12, one of the prevalent ones in humans in Argentina. Electrocardiography, heart histopathology, parasitemias, and survival in infected and reinfected mice were also analyzed. Reinfected mice reached higher parasitemias, 14% of the infected with SGO-Z12 and 76% of the reinfected groups showed electrocardiographic abnormalities. Similar results were found in mice that were infected and reinfected with Tul. SGO-Z12-Reinfected and Tul-Infected groups exhibited cardiac beta-adrenergic receptors' affinity significantly diminished (p<0.001) and its density significantly increased (p<0.001) than in infected and non-infected groups. Histopathologic alterations in hearts from Tul and SGO-Z12-Reinfected mice were detected. Reinfections with T. cruzi, Tulahuen strain or SGO-Z12 isolate provoked cardiac dysfunctions of different degrees, from the acute phase on.
Asunto(s)
Enfermedad de Chagas/fisiopatología , Modelos Animales de Enfermedad , Miocardio/metabolismo , Miocardio/patología , Receptores Adrenérgicos beta/metabolismo , Trypanosoma cruzi/patogenicidad , Enfermedad Aguda , Animales , Cardiomiopatía Chagásica/mortalidad , Cardiomiopatía Chagásica/parasitología , Cardiomiopatía Chagásica/patología , Enfermedad de Chagas/parasitología , Enfermedad Crónica , Progresión de la Enfermedad , Electrocardiografía , Femenino , Corazón/parasitología , Humanos , Ratones , Parasitemia/parasitología , Recurrencia , Tasa de SupervivenciaRESUMEN
Chagas' disease is caused by Trypanosoma cruzi, which is transmitted by reduviid bugs. The World Health Organization has estimated that about 16-18 million people in the Americas are infected, and that more than 100 million are at risk. In the present study we have used a murine model to analyse if particular T. cruzi strains (Tulahuen strain and SGO-Z12 isolate from a chronic patient) and/or re-infection may determine, during the indeterminate phase of experimental Chagas' disease, changes that could explain the different evolution of cardiac lesions. Re-infected mice reached higher parasitaemias than those infected for the first time. The survival in the indeterminate phase of mice infected with Tulahuen strain was 50.0%, while the SGO-Z12-infected group presented a significantly higher survival rate (77.1%; P <0.01). The SGO-Z12-re-infected group showed a survival rate (70.9%) significantly higher than that of the Tulahuen-re-infected group (37.0%; P <0.01). Electrocardiographic abnormalities were found in 66% of Tulahuen-infected mice, while in SGO-Z12-infected group such abnormalities were found in only 36% of animals ( P <0.01). The two groups exhibited similar percentages of electrocardiographic dysfunction on re-infection, although intraventricular blocks were more frequent in Tulahuen-re-infected mice ( P <0.01). Hearts from infected or re-infected mice with either parasite showed mononuclear infiltrates. The SGO-Z12-re-infected and Tulahuen-re-infected groups exhibited a significantly diminished affinity ( P <0.05) and a significantly increased density ( P <0.05) of cardiac beta-adrenergic receptors compared with the infected and non-infected groups. The indeterminate phase of Chagas' disease is defined as a prolonged period that is clinically silent, but the present findings show that different T. cruzi strains and re-infection are able to alter the host-parasite equilibrium, and these factors may be responsible for inducing progressive cardiopathy.