RESUMEN
Deficits in hippocampal synaptic plasticity result in cognitive impairment in Huntington's disease (HD). Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts neuroprotective actions, mainly through the PAC1 receptor. However, the role of PACAP in cognition is poorly understood, and no data exists in the context of Huntington's disease (HD). Here, we investigated the ability of PACAP receptor stimulation to enhance memory development in HD. First, we observed a hippocampal decline of all three PACAP receptor expressions, i.e., PAC1, VPAC1, and VPAC2, in two different HD mouse models, R6/1 and HdhQ7/Q111, from the onset of cognitive dysfunction. In hippocampal post-mortem human samples, we found a specific decrease of PAC1, without changes in VPAC1 and VPAC2 receptors. To determine whether activation of PACAP receptors could contribute to improve memory performance, we conducted daily intranasal administration of PACAP38 to R6/1 mice at the onset of cognitive impairment for seven days. We found that PACAP treatment rescued PAC1 level in R6/1 mice, promoted expression of the hippocampal brain-derived neurotrophic factor, and reduced the formation of mutant huntingtin aggregates. Furthermore, PACAP administration counteracted R6/1 mice memory deficits as analyzed by the novel object recognition test and the T-maze spontaneous alternation task. Importantly, the effect of PACAP on cognitive performance was associated with an increase of VGlut-1 and PSD95 immunolabeling in hippocampus of R6/1 mice. Taken together, these results suggest that PACAP, acting through stimulation of PAC1 receptor, may have a therapeutic potential to counteract cognitive deficits induced in HD.
Asunto(s)
Hipocampo/fisiopatología , Enfermedad de Huntington/fisiopatología , Memoria/fisiología , Plasticidad Neuronal/efectos de los fármacos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Administración Intranasal , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastornos del Conocimiento/fisiopatología , Modelos Animales de Enfermedad , Homólogo 4 de la Proteína Discs Large/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hipocampo/patología , Humanos , Proteína Huntingtina/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/administración & dosificación , Agregado de Proteínas , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/metabolismo , Proteína 1 de Transporte Vesicular de Glutamato/metabolismoRESUMEN
Objetivo Conocer la efectividad de una intervención farmacéutica en pacientes, al alta hospitalaria, para mejorar la comprensión de los tratamientos farmacológicos y en consecuencia el cumplimiento de las pautas prescritas, en su domicilio. Observar si esta intervención repercute en el número de reingresos hospitalarios. Método Estudio experimental, controlado, aleatorizado, con dos grupos paralelos. Fueron incluidos 100 pacientes polimedicados del área de medicina interna. Al grupo control no se le realizó ninguna actividad complementaria a la práctica clínica habitual. Al grupo intervención, ya sea paciente o cuidador en el caso de pacientes dependientes, un farmacéutico le explicó y le hizo entrega de un diagrama horario personalizado de los medicamentos prescritos. Además, se informó al paciente acerca de la utilidad de cada medicamento, cómo debía ser administrado y la importancia de seguir las pautas correctamente. Al cabo de siete días, todos los pacientes o cuidadores fueron entrevistados telefónicamente acerca de su medicación, mediante un cuestionario. Se compararon las respuestas obtenidas con la prescripción médica al alta y se registraron las discrepancias. Mediante el sistema informático del censo hospitalario se consultaron los reingresos a los treinta y sesenta días del alta hospitalaria. Resultados El 70,7% de pacientes del grupo intervención, a la semana del alta, tomaba toda su medicación conforme a las pautas prescritas, en el grupo control este porcentaje fue de 19,5% (p < 0,001). El número de pacientes que reingresaron en el hospital al mes del (..)(AU)
Objective To determine the effectiveness of a pharmaceutical intervention with the patient upon hospital discharge, to improve understanding of pharmaceutical treatment and, as a consequence, improve adherence to prescribed regimens at home. To observe whether this intervention has an impact on the number of hospital admissions. Methods Experimental, controlled, randomised study with two parallel groups. One-hundred polymedicated internal medicine patients were included. Routine clinical practice was performed on the control group. For the intervention group, whether patient or carer (in the case of dependent patients), a pharmacist explained the drugs prescribed giving the patient a personalised medication timetable. Furthermore, the pharmacist explained why each drug had been prescribed, how to take it and why it was important to take the medication correctly. After seven days, all patients or carers were asked to complete a questionnaire about their treatment by telephone. The responses obtained were compared with the prescription upon discharge and discrepancies were recorded. We consulted the hospital's computer records to check for admissions thirty and sixty days following discharge. Results A week following hospital discharge, 70.7% of the intervention group were taking all of their medication in accordance with the prescribed regimen, whereas 19.5% of the control group was (P < .001). Three (7.3%) patients from the intervention group and 10 patients (24.4%) from the control group were readmitted a month following hospital discharge (P < .05). After two months, 3 (7.2%) patients from the intervention group and 13 (31.7%) from the control group had been readmitted (P < .01).Conclusions The pharmacist's intervention upon discharge has helped increase the percentage of patients that understood and took their medication correctly in accordance with their prescription. The number of hospital readmissions in the intervention group has also reduced (AU)
Asunto(s)
Servicio de Farmacia en Hospital/organización & administración , Administración del Tratamiento Farmacológico/organización & administración , Servicios Farmacéuticos , Evaluación de Eficacia-Efectividad de Intervenciones , Alta del PacienteRESUMEN
OBJECTIVE: To determine the effectiveness of a pharmaceutical intervention with the patient upon hospital discharge, to improve understanding of pharmaceutical treatment and, as a consequence, improve adherence to prescribed regimens at home. To observe whether this intervention has an impact on the number of hospital admissions. METHODS: Experimental, controlled, randomised study with two parallel groups. One-hundred polymedicated internal medicine patients were included. Routine clinical practice was performed on the control group. For the intervention group, whether patient or carer (in the case of dependent patients), a pharmacist explained the drugs prescribed giving the patient a personalised medication timetable. Furthermore, the pharmacist explained why each drug had been prescribed, how to take it and why it was important to take the medication correctly. After seven days, all patients or carers were asked to complete a questionnaire about their treatment by telephone. The responses obtained were compared with the prescription upon discharge and discrepancies were recorded. We consulted the hospital's computer records to check for admissions thirty and sixty days following discharge. RESULTS: A week following hospital discharge, 70.7% of the intervention group were taking all of their medication in accordance with the prescribed regimen, whereas 19.5% of the control group was (P < .001). Three (7.3%) patients from the intervention group and 10 patients (24.4%) from the control group were readmitted a month following hospital discharge (P < .05). After two months, 3 (7.2%) patients from the intervention group and 13 (31.7%) from the control group had been readmitted (P < .01). CONCLUSIONS: The pharmacist's intervention upon discharge has helped increase the percentage of patients that understood and took their medication correctly in accordance with their prescription. The number of hospital readmissions in the intervention group has also reduced.
Asunto(s)
Cuidados Posteriores/métodos , Consejo Dirigido , Cumplimiento de la Medicación , Alta del Paciente , Educación del Paciente como Asunto/métodos , Servicio de Farmacia en Hospital , Anciano , Anciano de 80 o más Años , Cuidadores/psicología , Esquema de Medicación , Femenino , Humanos , Masculino , Errores de Medicación/prevención & control , Readmisión del Paciente/estadística & datos numéricos , Pacientes/psicología , Farmacéuticos , Polifarmacia , Rol Profesional , Encuestas y Cuestionarios , TeléfonoRESUMEN
INTRODUCTION: Atopic dermatitis (AD) is a cutaneous disease of unknown etiology. It shows a clear genetic predisposition with probable environmental modulation. This study evaluated risk factors associated with diagnosis and flares of AD in Spanish children. PATIENTS AND METHODS: We performed an observational, multicenter, retrospective case-control study that included 4243 children aged less than 14 years old with AD and 978 controls matched for age and sex. Family history of disease and environmental variables were collected in both groups and clinical history of AD was recorded in the case group. RESULTS: Significant risk factors for AD were: a family history of the disease and concomitant cutaneous infections. The prevalence of AD in first degree relatives was 39 % and that in second degree relatives was 19 % (higher in maternal than paternal lines). The mean age of children with AD was 4.2 (SD 3.4) years and the mean age at diagnosis was 1.5 (SD 2.2) years, with a mean of 2.9 (SD 2.6) flares during the previous year. Cold weather (Cantabrian and Continental Iberian Peninsula areas) was related to a greater number of flares. Children with AD had a greater number of concomitant cutaneous diseases and infections than children in the control group. CONCLUSIONS: AD is mainly a genetic disease, with climatic factors involved in severity modulation, and with important immunological alterations. In contrast, this study found no domestic environmental factors that were associated with disease onset.
Asunto(s)
Dermatitis Atópica/epidemiología , Dermatitis Atópica/genética , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , España/epidemiologíaRESUMEN
Introducción: La dermatitis atópica (DA) es una enfermedad de etiología desconocida, con clara predisposición genética y una probable participación de factores ambientales. El objetivo del estudio era evaluar los factores de riesgo asociados al diagnóstico y aparición de brotes de DA en niños españoles. Pacientes y métodos: Estudio observacional, multicéntrico, retrospectivo de casos y control que incluyó una muestra de 4.243 niños menores de 14 años afectados de DA y 978 controles ajustados por edad y sexo. Se recogieron datos de antecedentes familiares y características del entorno familiar en ambos grupos y características clínicas de la DA en los pacientes. Resultados: Los factores de riesgo significativos para la aparición de DA fueron los antecedentes familiares y las infecciones concomitantes de la piel. La prevalencia de DA en familiares de primer grado fue del 39 % y en familiares de segundo grado, del 19 % (superior en línea materna que paterna). La edad media de los niños afectados fue de 4,2 (desviación estándar [DE] 3,4) años y la edad media en el diagnóstico fue de 1,5 (DE 2,2) años, con un número medio de brotes de la enfermedad de 2,9 (DE 2,6) en el año previo. En las zonas de España con clima más frío (cantábrico y continental) se observó mayor número de brotes. Los niños con DA presentaron mayor coincidencia de enfermedades cutáneas e infecciosas que los niños control. Conclusiones: La DA es una enfermedad con una gran predisposición genética, modulada por factores climáticos y que acarrea alteraciones inmunológicas. Por el contrario no encontramos influencias significativas de factores ambientales domésticos
Introduction: Atopic dermatitis (AD) is a cutaneous disease of unknown etiology. It shows a clear genetic predisposition with probable environmental modulation. This study evaluated risk factors associated with diagnosis and flares of AD in Spanish children. Patients and methods: We performed an observational, multicenter, retrospective case-control study that included 4243 children aged less than 14 years old with AD and 978 controls matched for age and sex. Family history of disease and environmental variables were collected in both groups and clinical history of AD was recorded in the case group. Results: Significant risk factors for AD were: a family history of the disease and concomitant cutaneous infections. The prevalence of AD in first degree relatives was 39 % and that in second degree relatives was 19 % (higher in maternal than paternal lines). The mean age of children with AD was 4.2 (SD 3.4) years and the mean age at diagnosis was 1.5 (SD 2.2) years, with a mean of 2.9 (SD 2.6) flares during the previous year. Cold weather (Cantabrian and Continental Iberian Peninsula areas) was related to a greater number of flares. Children with AD had a greater number of concomitant cutaneous diseases and infections than children in the control group. Conclusions: AD is mainly a genetic disease, with climatic factors involved in severity modulation, and with important immunological alterations. In contrast, this study found no domestic environmental factors that were associated with disease onset
Asunto(s)
Lactante , Niño , Adolescente , Preescolar , Humanos , Dermatitis Atópica/epidemiología , Dermatitis Atópica/genética , Prevalencia , Factores de Riesgo , España/epidemiologíaRESUMEN
In the female reproductive tract, the complement system represents a defense mechanism that can act directly against pathogens and cells, and mediates inflammatory response. Endometrial cells are protected from autologous complement attack by membrane-bound complement regulatory proteins (CRPs) that prevent complement activation: membrane cofactor protein (CD46), decay accelerating factor (CD55), and protectin (CD59). In this work we show that all CRPs were overexpressed after LPS exposure. Maximal stimulatory effect was detected after 6h, and was declining after 12h, reaching control levels in 24h. CD59 was the protein showing the more prominent effect. There seems to be a slight increase of CRP expression in the endometrium of sterile patients that have anti-endometrial antibodies (AEA) in their serum. Our results suggest that under stress, the high expression of CRPs (CD46, CD55, and CD59) could protect endometrial injured cells against complement mediated lysis. The survival of these cells with some biochemical modifications would enable autoimmune response.