ABSTRACT
BACKGROUDS: Cannabinoid receptor antagonists have been suggested as a novel treatment for obesity and diabetes. We have developed a synthetic cannabinoid receptor antagonist denominated BAR-1. As the function and integrity of a ß-cell cellular structure are important keys for diabetes onset, we evaluated the effects of pharmacological administration of BAR-1 on prediabetic and diabetic rodents. METHODS: CD-1 mice fed a hypercaloric diet or treated with streptozotocin were treated with 10 mg/kg BAR-1 for 2, 4 or 8 weeks. Body weight, oral glucose tolerance test, HbA1c, triglycerides and insulin in serum were measured. In isolated islets, we evaluated stimulated secretion and mRNA expression, and relative area of islets in fixed pancreases. Docking analysis of BAR-1 was complemented. RESULTS: BAR-1 treatment slowed down weight gain in prediabetic mice. Fasting glucose-insulin relation also decreased in BAR-1-treated mice and glucose-stimulated insulin secretion was increased in isolated islets, without effects in oral test. Diabetic mice treated with BAR-1 showed a reduced glucose and a partial recovery of islet integrity. Gene expression of insulin and glucagon showed biphasic behaviour, increasing after 4 weeks of BAR-1 administration; however, after 8 weeks, mRNA abundance decreased significantly. Administration of BAR-1 also prevents changes in endocannabinoid element expression observed in prediabetic mice. No changes were detected in other parameters studied, including the histological structure. A preliminary in-silico study suggests a close interaction with CB1 receptor. CONCLUSIONS: BAR-1 induces improvement of islet function, isolated from both prediabetic and diabetic mice. Effects of BAR-1 suggest a possible interaction with other cannabinoid receptors.
Subject(s)
Cannabinoid Receptor Antagonists/pharmacology , Diabetes Mellitus, Experimental/metabolism , Islets of Langerhans/drug effects , Prediabetic State/metabolism , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Animals , Body Weight/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/pathology , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Insulin/blood , Insulin Secretion/drug effects , Male , Mice , Prediabetic State/drug therapy , Prediabetic State/pathology , Receptor, Cannabinoid, CB1/administration & dosage , Streptozocin , Triglycerides/bloodABSTRACT
La depresión en adolescentes constituye un problema de salud pública por su frecuencia creciente y sus consecuencias. Objetivo: Determinar las prevalencias y los factores asociados con el episodio depresivo en adolescentes de las ciudades de Cajamarca, Huaraz y Ayacucho. Material y Métodos: Estudio epidemiológico de corte transversal, con muestreo probabilístico trietápico por conglomerados. Se usó la base de datos del Estudio Epidemiológico en Salud Mental de la Sierra Peruana 2003. La población estudiada comprendió a los residentes de 12 a 17 años. Se utilizaron cuestionarios para medir variables demográficas y socioeconómicas, aspectos generales de salud mental, trastornos clínicos y relaciones intrafamiliares. Se ajustaron modelos de regresión logística múltiple. Resultados: La prevalencia de episodio depresivo en adolescentes fue 5,7% (IC 95%: 4,5%-7,2%), observándose según el análisis multivariado, asociaciones estadísticamente significativas con: sexo femenino (OR: 2,7, IC 95%: 1,4-5,2), haber tenido enamorado(a) (OR: 2,3, IC 95%: 1,2-4,1), síndrome psicótico (OR: 5,3, IC 95%: 2,2-13,2) y deseos de morir (OR: 3,2, IC 95%: 1,8-5,8). Conclusiones: La prevalencia de episodio depresivo en adolescentes de las tres ciudades estudiadas fue similar a la encontrada en otros países. Los factores asociados que mejor predijeron el episodio depresivo fueron: sexo femenino, haber tenido enamorado(a), síndrome psicótico y deseos de morir alguna vez en la vida; los cuales podrían ser evaluados como factores de riesgo en estudios posteriores.
Adolescent depression is a public health problem due to its increasing frequency and consequences. Objective: To determine the prevalence of depressive episode and associated factors in adolescents from the cities of Cajamarca, Huaraz and Ayacucho. Material and Methods: Cross sectional study with three-stage cluster probability sampling. We used the database of the Mental Health Epidemiological Study from the Peruvian Andes 2003. The population from 12 to 17 years old was assessed. Questionnaires were used to measure demographic and socioeconomic variables, general mental health, mental disorders and domestic relationships. We adjusted multiple logistic regression models. Results: Prevalence of depressive episode in adolescents was 5.7% (IC 95%: 4.5%-7.2%). We observed by multivariate analysis, statistically significant associations with: female gender (OR: 2.7, IC 95%: 1.4-5.2), having had a boyfriend or girlfriend (OR: 2.3, IC 95%: 1.2-4.1), psychotic syndrome (OR: 5.3, IC 95%: 2.2-13.2) and the wish to die (OR: 3.2, IC 95%: 1.8-5.8). Conclusions: Prevalence of depressive episode in adolescents in these three cities was similar to those reported in adolescents in other countries. Associated factors that best predicted depressive episode were female gender, having had a boyfriend or girlfriend, psychotic syndrome and wish to die, which should be evaluated as risk factors in future studies.
Subject(s)
Humans , Male , Female , Adolescent , Depression , Precipitating Factors , Prevalence , Epidemiologic Studies , Cross-Sectional Studies , Cluster Sampling , PeruABSTRACT
La depresión en adolescentes constituye un problema de salud pública por su frecuencia creciente y sus consecuencias. Objetivo: Determinar la prevalencia y los factores asociados con el episodio depresivo en adolescentes de Lima Metropolitana y Callao. Métodos: Estudio de corte transversal, con muestreo probabilístico trietápico por conglomerados. Se usó la base de datos del Estudio Epidemiológico Metropolitano en Salud Mental 2002. La población estudiada comprendió a los residentes de 12 a 17 años. Se utilizaron cuestionarios para medir variables demográficas y socioeconómicas, aspectos generales de salud mental, trastornos clínicos y relaciones intrafamiliares. Se ajustaron modelos de regresión logística múltiple. Resultados: La prevalencia actual del episodio depresivo en adolescentes fue 8.6% (IC 95%: 6.7-11.1%), observándose según el análisis multivariado, asociaciones estadísticamente significativas con: edad de 15 a 17 años (OR: 2.03; IC 95%: 1.08-3.98), sexo femenino (OR: 2.24; IC 95%: 1.16-4.29), nada o poca satisfacción con las relaciones sociales (OR: 2.69; IC 95%: 1.33-5.46), reglas y castigos en el hogar injustos (OR: 4.22; IC 95%: 2.15-8.26), problemas alimentarios (OR: 3.0; IC 95%:1.39-6.45) y deseos de morir (OR: 2.88; IC 95%:1.51-5.51). Conclusiones: La prevalencia del episodio depresivo en adolescentes de Lima Metropolitana y Callao fue similar y en algunos casos mayor a la encontrada en adolescentes de otros países. Los factores asociados que mejor predijeron el episodio depresivo fueron: edad de 15 a 17 años, sexo femenino, nada o poca satisfacción con las relaciones sociales, reglas y castigos en el hogar injustos, problemas alimentarios y deseos de morir; los cuales podrían ser evaluados como factores de riesgo en estudios posteriores.
Objective: To determine the prevalence and factors associated with depressive episode in adolescents from Lima Metropolitana and Callao. Methods: Cross sectional study with three-stage cluster probability sampling. We used the database from the Metropolitan Epidemiological Study on Mental Health 2002. Study population comprised residents of 12-17 years. Questionnaires were used to measure demographic and socioeconomic variables, general mental health, mental disorders and domestic relationships. We adjusted multiple logistic regression models. Results: Prevalence of depressive episode in adolescents was 8.6% (CI 95%: 6.7-11.1%), we observed, by multivariate analysis, statistically significant associations with age of 15-17 years (OR: 2.028; CI 95%: 1.084-3.984), female gender (OR: 2.24; CI 95% 1.164-4.292), nothing or little satisfaction with social relationships (OR: 2.691; CI 95%: 1.326-5.460), unjust rules and punishment at home (OR: 4.215; CI 95%: 2.151-8.26), eating disorders (OR: 3.0; CI 95%: 1.394-6.454) and death wishes (OR:2.88; CI 95%: 1.505-5.511). Conclusions: Prevalence of depressive episode in adolescents in Lima and Callao was similar and in some cases greater than prevalence reported in adolescents in other countries. Associated factors that best predicted depressive episode were age 15 to 17 years, female gender, nothing or little satisfaction with social relationships, unjust rules and punishment at home, eating disorders and wishes to die, which could be evaluated as risk factors in future studies. Keywords: Depression, Adolescents, Prevalence, Associated factors.
