The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice

The endocannabinoid system (ECS) regulates energy metabolism, has been implicated in the pathogenesis of metabolic diseases and exerts its actions mainly through the type 1 cannabinoid receptor (CB1). Likewise, autophagy is involved in several cellular processes. It is required for the normal development of muscle mass and metabolism, and its deregulation is associated with diseases. It is known that the CB1 regulates signaling pathways that control autophagy, however, it is currently unknown whether the ECS could regulate autophagy in the skeletal muscle of obese mice. This study aimed to investigate the role of the CB1 in regulating autophagy in skeletal muscle. We found concomitant deregulation in the ECS and autophagy markers in high-fat diet-induced obesity. In obese CB1-KO mice, the autophagy-associated protein LC3 II does not accumulate when mTOR and AMPK phosphorylation levels do not change. Acute inhibition of the CB1 with JD-5037 decreased LC3 II protein accumulation and autophagic flux. Our results suggest that the CB1 regulates autophagy in the tibialis anterior skeletal muscle in both lean and obese mice.

Sistema endocanabinoide y desarrollo de esteatosis hepática / A role for the endocannabinoid system in hepatic steatosis

The endocannabinoid system (SEC) is an important modulator of several metabolic functions. This system is composed by cannabinoid receptors type 1 and 2 (RCB1 and RCB2), their endogenous ligands, known as endocannabinoids, and the enzymes involved in their synthesis and degradation. A deregulated SEC originates metabolic alterations in several tissues, resulting in the typical manifestations of the metabolic syndrome. Liver steatosis of different origins constitutes a physiopathological condition where an altered hepatic SEC is observed. In this condition, there is an increased expression of RCB1 and/or higher endocannabinoid levels in different hepatic cells, which may exert an autocrine/paracrine hyperstimulation of RCB1/RCB2. Activation of RCB1 stimulate the expression of several hepatocyte lipogenic factors, thus leading to increased de novo fatty acids synthesis and consequently to an abnormal accumulation of triglycerides. The effect of RCB2 activity on hepatic function is still controversial because, on one side its stimulation has an interesting protective effect on alcoholic liver disease while, on the other, it may enhance the development of hepatic steatosis in experimental models of diet-induced obesity. In this review we discuss the proposed mechanisms by which SEC is involved in the etiology of hepatic steatosis, as well as the therapeutic possibilities involving peripheral RCB1/RCB2 antagonism/agonism, for the treatment of this condition.

Factores asociados a síntomas depresivos en trabajadoras sexuales / Factors associated to depression symptomatology in sex workers

Introducción: Las condiciones de trabajo y la violencia ejercida contra las trabajadoras sexuales han sido relacionadas con el incremento de las tasas de infecciones de transmisión sexual. Sin embargo, también se encuentran enfermedades que afectan su salud mental. Objetivos: Determinar la magnitud de síntomas depresivos y factores asociados en trabajadoras sexuales. Diseño: Estudio transversal-analítico. Lugar: Centro de salud referencial para la prevención y control de infecciones de transmisión sexual. Participantes: Trabajadoras sexuales. Intervenciones: A 117 trabajadoras sexuales, que fueron atendidas durante los meses de mayo y junio del 2010, se aplicó el test de Beck para medir la sintomatología depresiva y una encuesta para medir los siguientes factores: socio-demográficos, sociales (antecedentes de maltrato físico, psicológico y sexual en el trabajo y hábitos nocivos: alcohol y drogas), conductas sexuales de riesgo y características del trabajo (edad de inicio, años de trabajo, satisfacción con el trabajo). Principales medidas de resultados: Porcentaje de síntomas depresivos y fuerza de asociación entre los factores y la presencia de síntomas depresivos. Resultados: El 56,4 por ciento de las trabajadoras sexuales presentó algún nivel de sintomatología depresiva. El nivel de síntomas depresivos graves estuvo presente en 23,9 por ciento. Los factores que se encontraron asociados a depresión, independiente del nivel, fue el antecedente de maltrato físico frecuente, con OR=9,46, IC95 por ciento 1,05 a 85,07; p=0,045. Los factores asociados a nivel de síntomas depresivos graves fueron: ingreso económico menor a S/. 1 000.00, tener hijos, haberse iniciado en el trabajo sexual antes de los 18 años y consumo de drogas (p<0,05). Conclusiones: Más de 50 por ciento de trabajadoras presentó algún nivel de síntomas depresivos, que estuvieron asociados al antecedente de maltrato físico. Para el nivel síntomas depresivos graves, los factores asociados fueron: ingreso económico menor a S/. 1 000.00, tener hijos, haberse iniciado en el trabajo sexual antes de los 18 años y consumir drogas.

Introduction: The working conditions and violence against sex workers has been linked to increasing rates of sexual transmitted diseases. But there are also other diseases that affect their mental health. Objectives: To determine the magnitude of depressive symptoms and associated factors in sex workers. Design: Crossanalytic study. Setting: Health Centre of reference for the prevention and control of sexually transmitted infections. Participants: Sex workers. Interventions: Beck test was applied to 117 sex workers attended between May and June 2010 in order to measure depressive symptoms as well as a survey to determine socio-demographic and social (physical abuse, psychological and sexual labor and harmful habits: alcohol and drug abuse) factors, risky sexual behavior and job characteristics (age at onset, years of work, job satisfaction). Main outcome measures: Percentage of depressive symptoms and weight of association between factors and presence of depressive symptoms. Results: Some level of depressive symptoms was found in 56,4 per cent of sex workers. Severe depressive symptoms were present in 23,9 per cent. Main factor associated with depression was background of frequent physical abuse (OR = 9,46, CI95 per cent: 1,05 to 85,07; p = 0,045). Factors associated with severe depressive symptoms were income less than S/. 1 000.00, having children, having started sex work before age 18, and drug abuse (p <0,05). Conclusions: Over 50 per cent of sex workers had some level of depressive symptoms generally associated with history of physical abuse. Severe depressive symptoms were associated to income less than S/. 1 000.00, having children, having started sex work before age 18, and drug abuse.

Participación del sistema endocanabinoide en el desarrollo de obesidad / A role for the endocannabinoid system in obesity

Endocannabinoids are the endogenous ligands for the cannabinoid receptors type 1 and 2. These membrane receptors are responsible for the psychotropic effects of Cannabis Sativa, when bound to its active component known as (-)-Δ9-tetrahydro-cannabinol. Cannabinoid receptors, endocannabinoids and the enzymes catalyzing their biosynthesis and degradation, constitute the endocannabinoid system (ECS), which has a remarkable role controlling energy balance, both at central nervous system and peripheral tissues. The ECS regulates food ingestion by stimulating a network of orexigenic neurons present in the hypothalamus and reinforcing motivation and reward to food consumption in the nucleus accumbens. Regarding peripheral tissues, this system controls lipid and glucose metabolism at different levels, reduces energy expenditure and leads energy balance to fat storage. Metabolic alterations, includ-ing excessive accumulation of abdominal fat, dyslipidaemia and hyperglicaemia, are suggested to be associated to a hyperactivated ECS. Since obesity is one of the major health problems in modern societies, in this review we discuss the role of the endocannabinoid system in metabolic pathways associated to control mechanisms of energy balance and its involvement in overweight and obesity. In addition, we also discuss therapeutic possibilities and emergent problems due to cannabinoid receptor type 1 antagonism utilized as treatment for such alterations.

Neurofibromatosis tipo 1 asociada a déficit cognitivo, hidrocefalia, displasia ósea y elefantiasis / Neurofibromatosis type 1 associated to cognition deficit, hydrocephaly, bone dysplasia and elephantiasis

Se presenta el caso de un paciente varón de 31 años, procedente de Cajamarca, con problemas cognitivos desde su escolaridad temprana, que desde los 12 años desarrolló incremento progresivo de volumen y deformación de su miembro inferior derecho y en menor cuantía del izquierdo, asociado a plegamiento de piel, crecimiento de nódulos subcutáneos, con formación de cordones nerviosos en muslo y pierna que le daban un aspecto elefantiásico. Dolor y limitación funcional para la marcha. Concomitantemente, presencia en piel de manchas café con leche generalizadas y nódulos de Lisch en ambos iris. En la resonancia magnética y TAC con contraste, se evidenciaron abundantes nódulos plexiformes en cavidad abdominopélvica, que continuaban por todo el muslo, de tamaño uniforme, formando tumoraciones y cordones. Asimismo, presentó displasia ósea (adelgazamiento de la cortical del fémur y tibia, formación de neocótilo izquierdo, pseudoartrosis). La resonancia cerebral con contraste descubrió una hidrocefalia triventricular, normotensa.

We report the case of a 31 year-old male from Cajamarca, Peru, with cognitive problems since childhood, who at 12 year-old developed increased volume and deformation of his right lower limb and to a lesser extent of his left, associated to massive skin folding, growth of subcutaneous nodules, elephantine look due to nerve cords formation in thigh and leg, pain and functional walking limitation. Concomitantly generalized skin café au lait spots, subcutaneous nodules, and Lisch nodules in both irides. Magnetic resonance and contrast TAC revealed abundant uniform plexiform nodules in abdomino-pelvic cavity forming masses and cords that continued throughout his thigh as lumps and cords. In addition, the patient presented bone dysplasia (thinning of femur and tibia cortex, pseudoarthrosis, new left cotyle formation). Contrast magnetic resonance showed triventricular normotensive hydrocephalus.

Evidencias de la presencia de una actividad tipo-quimotripsina en el espermatozoide humano y su rol en la reacción acrosómica / Evidence of the quimiotrypsin activity in the human spermatozoid and its role in the acrosomic reaction

Se evaluó el efecto de inhibidores de la quimotripsina sobre la reacción acrosómica del espermatozoide humano estimulada por la zona pelúcida o fluido folicular humano. Espermatozoides mótiles, seleccionados por un gradiente de Percol, fueron incubadas en una concentración de 1x 10 células/ml, a 37 grados centigrados, y 5 por ciento de CO2. Después de 4.5 hrs. Se añadió el inhibidor de quimotripsina TPCK (N- Tosyl-L-Phenylalanine-Chloromethyl Ketone) o el sustrato ATEE (N-Acetyl-L-Tyrosine Ethyl Ester) por 30 minutos. Luego, se añadieron cuatro ovocitos humanos y se determinó el porcentaje de reacción acrosómica sobre la zona pelúcida. El TPCK y el ATEE inhibieron la reacción acrosómica producida por la zona pelúcida. Los inhibidores de quimotripsina TPCK y quimostatina y los sustratos para quimotripsina ATEE, BTEE (N-Benzoyl-Tyrosine-Ethyl Esther), Succinyl-Ala-Ala-Phe-7-Amido-4 Methyl-Coumarin (Suc-Ala-Ala-Phe-AMC), y Succynil-Leu-Leu-Val-Try-7-Amido-4 Methyl-Coumarin (Suc-Leu-leu-Val-Tyr-AMC) inhibieron la reacción acrosómica inducida por el fluido folicular humano. Los extractos espermáticos mostraron una actividad hidrolítica hacia los sustratos Suc-Ala-Ala-Phe-AMC y Suc-Leu-Leu-Val-Tyr-AMC. Esta actividad enzimática fue anulada por el TPCK y la quimostatina, en ausencia de Ca2+ y no fue modificada por la 1,10 fenantrolina. Además, esta actividad estuvo presente en el sobrenadante después de que la reacción acrosómica fue inducida por el ionóforo de calcio y en espermatozoides epidídimales recuperados de la región caudal. Observaciones con el microscopio electrónico indicaron que los inhibidores impidieron los eventos de membrana de la reacción acrosómica. Estos datos sugieren una asociación entre el espermatozoide humano y una actividad tipo quimotripsina con un posible rol en la reacción acrosómica