Mitochondrial dysfunction in non-alcoholic fatty liver disease and insulin resistance: cause or consequence?

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome and refers to a spectrum of disorders ranging from steatosis to steatohepatitis, a disease stage characterized by inflammation, fibrosis, cell death and insulin resistance (IR). Due to its association with obesity and IR the impact of NAFLD is growing worldwide. Consistent with the role of mitochondria in fatty acid (FA) metabolism, impaired mitochondrial function is thought to contribute to NAFLD and IR. Indeed, mitochondrial dysfunction and impaired mitochondrial respiratory chain have been described in patients with non-alcoholic steatohepatitis and skeletal muscle of obese patients. However, recent data have provided evidence that pharmacological and genetic models of mitochondrial impairment with reduced electron transport stimulate insulin sensitivity and protect against diet-induced obesity, hepatosteatosis and IR. These beneficial metabolic effects of impaired mitochondrial oxidative phosphorylation may be related not only to the reduction of reactive oxygen species production that regulate insulin signaling but also to decreased mitochondrial FA overload that generate specific metabolites derived from incomplete FA oxidation (FAO) in the TCA cycle. In line with the Randle cycle, reduced mitochondrial FAO rates may alleviate the repression on glucose metabolism in obesity. In addition, the redox paradox in insulin signaling and the delicate mitochondrial antioxidant balance in steatohepatitis add another level of complexity to the role of mitochondria in NAFLD and IR. Thus, better understanding the role of mitochondria in FA metabolism and glucose homeostasis may provide novel strategies for the treatment of NAFLD and IR.

Paclitaxel-induced neuropathic pain is age dependent and devolves on glial response.

BACKGROUND: Paclitaxel is an antimitotic antitumour drug highly effective against a broad range of cancers considered refractory to conventional chemotherapy. One of the main serious side effects of paclitaxel treatment is the induction of peripheral neuropathic pain that often diminishes the patient's quality of life. In this study, we evaluated the severity of the neuropathy induced by paclitaxel and the inflammatory reaction in the dorsal horn of the spinal cord in young, adult and aged male CD1 mice. METHOD: Hyperalgesia to noxious thermal stimulus and allodynia to non-noxious mechanical stimulus were evaluated using the plantar test and the von Frey filament model, respectively. Spinal cord microglia and astrocytes expression was assessed using Iba1 and glial fibrillary acidic protein immunofluorescence staining, respectively. RESULTS: All groups of mice showed a higher nociceptive reaction to thermal noxious (hyperalgesia) and mechanical non-noxious (allodynia) stimuli after paclitaxel treatment. However, these signs of neuropathy were enhanced in young mice followed by aged animals. Additionally, paclitaxel evoked a marked microglial and astrocytic response in the spinal cord of young and aged mice, whereas this enhanced reactivity was less important in adult mice. Indeed, the most severe glial activation observed in juvenile animals correlated well with major signs of neuropathy in this group of age. CONCLUSION: Our results demonstrate that paclitaxel-induced neuropathy in mice is an age-dependent phenomenon whose severity devolves on glial response.

Diferencias en el uso de las estrategias de afrontamiento, el catastrofismo y el estado de ánimo en función del tiempo de evolución del dolor crónico / No disponible

Introducción: este estudio describe el dolor crónico como un estresor complejo al que la persona debe adaptarse continuamente usando diferentes estrategias. Método: el objetivo de esta investigación es observar las diferencias que existen en las variables psicológicas y el uso de las estrategias de afrontamiento del dolor en función del tiempo de evolución. Los instrumentos de evaluación son: "Cuestionario del Dolor McGill" (MPQ), "Estrategias de Afrontamiento del Dolor Crónico" (CADR), "Escala Hospitalaria de Ansiedad y Depresión" (HAD), "Escala de Catastrofismo del CSQ" (CSQ-C). Los 60 participantes del estudio son pacientes de una unidad de tratamiento especializada en el ámbito hospitalario. De estos se crearon dos grupos, uno de menor tiempo de evolución (de 1 a 5 años) y el otro de mayor tiempo de evolución (de más de 13 años). Resultados: los resultados muestran que tanto el tiempo de evolución como la edad del paciente se asocian con el uso de una estrategia pasiva, la "catarsis" y la evaluación del dolor tiene una relación positiva con el catastrofismo, las estrategias pasivas, la ansiedad y la depresión. Mediante el análisis de la comparación de medias de los dos grupos se confirma que el grupo de menor tiempo de evolución hace mayor uso de la estrategia de afrontamiento "catarsis" y además presenta puntuaciones más altas en "catastrofismo" en comparación con los componentes del otro grupo. Conclusión: se observa la relación entre del dolor y las variables psicológicas del estudio como también los cambios que pueden aparecer en diferentes etapas de la evolución del dolor

Introduction: preliminary study on the psychological variables and coping strategies in chronic pain related to duration. This study describes chronic pain as a stressor complex that the person using a coping strategies to adapt continuously. Method: the primary objective of this research observes differences in psychological variables and the use of pain coping strategies depending on the time of evolution. The assessment instruments are McGill Pain Questionnaire (MPQ), "Strategies for Coping with Chronic Pain" (CADR), Hospital Anxiety and Depression Scale (HAD), Catastro-phism Scale CSQ (CSQ-C). Participants of this study are patients with chronic pain and are treated in to specialized unit. The results show that duration and patient's age are associated with the use of a passive strategy, the "catharsis". The perception of pain has a positive relationship with catastrophizing, passive strategies, anxiety and depression. Results: results obtained by comparing the average of the two groups, one with 1 to 5 years of evolution, and another 13 to 33 years, show that the group of shorter duration makes greater use of the coping strategy of catharsis and it has scored higher on catastrophizing compared to another group. Conclusion: we observe the relationship between pain and psychological variables of this study and changes that may occur in different stages of duration of pain (AU)

[Assessment of the effectiveness of an instrument to identify health an social problems in an elderly population from a primary health care center]. / Evaluación de la efectividad de un instrumento para identificar problemas sociales y sanitarios en la población anciana adscrita a un centro de atención primaria.

OBJECTIVE: To assess the response rate to a multi-dimensional, self administered questionnaire in patients > or =75 years old attending a primary health care center and to establish the prevalences of problems in the following dimensions: socio-economical, cognitive, morbidity, polypharmacy, physical activity, falls, and activities of the daily living. DESIGN: Cross-sectional descriptive study based on a self-administered questionnaire posted by mail. SETTING: A primary health care center in Barcelona. PARTICIPANTS: A total of 1299 patients > or =75 years old. MAIN MEASUREMENTS: Social surroundings, activities of the daily living, sensorial problems, morbidity, physical symptoms including sphincter's incontinence, cognitive status, and medication use. RESULTS: The response rate was 68% (95% CI, 0.65-0.70). The average age of the women who participated was significantly greater than the one of the men (82.5+/-5.3 vs 81.6+/-5.0, respectively). A significantly greater proportion of women than of men lived single (38.2 vs 10.9%); they had difficulties to maintain its house cosy (15.6 vs 8.8%) and they had difficulties to make ends meet (18.0 vs 13.6%). Globally, there were a greater proportion of women than of men whom they had: medical problems, cognitive problems, depression, and difficulties to carry out activities of the daily living. Overall, subjects that have had difficulties to make ends meet had greater prevalences of problems in all the dimensions of this evaluation. On the other hand, subjects that lived single had lower prevalences of problems in all the dimensions except they had a greater prevalence of depression. CONCLUSION: The multidimensional evaluation in elderly patients by the postal method is an efficient procedure that allows identifying many socioeconomic and health problems. In addition, it is feasible to identify to most fragile subjects and latter on to carry out preventive and curative interventions on them as well as to make their follow up.

Evaluación de la efectividad de un instrumento para identificar problemas sociales y sanitarios en la población anciana adscrita a un centro de atención primaria / Assessment of the effectiveness of an instrument to identify health an social problems in an elderly population from a primary health care centre

Diseño. Estudio descriptivo, transversal, basado en cuestionario autoadministrado enviado por correo postal. Emplazamiento. Un centro de atención primaria de Barcelona. Participantes. Un total de 1.299 ancianos de 75 años de edad o mayores. Mediciones principales. Entorno social, actividades de la vida diaria, problemas sensoriales, morbilidad, síntomas físicos, entre ellos, incontinencia de esfínteres, estado cognitivo y uso de medicación. Resultados. La tasa de respuesta fue del 68%. La edad promedio (± desviación estándar) de las mujeres que participaron fue significativamente mayor que la de los varones (82,5 ± 5,3 frente a 81,6 ± 5,0 años, respectivamente). Una proporción significativamente mayor de mujeres que de varones vivían solas (el 38,2 frente al 10,9%), tenían dificultades para mantener su casa acogedora (el 15,6 frente al 8,8%) y llegar a final de mes con suficientes recursos monetarios (el 18,0 frente al 13,6%). Globalmente, hubo una mayor proporción de mujeres que de varones que presentaban problemas médicos, problemas cognitivos, depresión y dificultades para llevar a cabo actividades de la vida diaria. Los sujetos que tenían dificultades para llegar a final de mes con suficientes recursos monetarios también presentaron globalmente mayores prevalencias de problemas en todas las dimensiones de esta evaluación. Los sujetos que vivían solos tenían una prevalencia menor de problemas en todas las dimensiones, pero una prevalencia mayor de depresión. Conclusión. La evaluación multidimensional en ancianos por correo postal es un procedimiento eficaz que permite identificar múltiples problemas sociales y sanitarios. Además, es factible identificar a los más frágiles, para posteriormente realizar intervenciones preventivas y curativas, así como su seguimiento

Objective. To assess the response rate to a multi-dimensional, self administered questionnaire in patients >=75 years old attending a primary health care center and to establish the prevalences of problems in the following dimensions: socio-economical, cognitive, morbidity, polypharmacy, physical activity, falls, and activities of the daily living. Design. Cross-sectional descriptive study based on a self-administered questionnaire posted by mail. Setting. A primary health care center in Barcelona. Participants. A total of 1299 patients >=75 years old. Main measurements. Social surroundings, activities of the daily living, sensorial problems, morbidity, physical symptoms including sphincter's incontinence, cognitive status, and medication use. Results. The response rate was 68% (95% CI, 0.65-0.70). The average age of the women who participated was significantly greater than the one of the men (82.5±5.3 vs 81.6±5.0, respectively). A significantly greater proportion of women than of men lived single (38.2 vs 10.9%); they had difficulties to maintain its house cosy (15.6 vs 8.8%) and they had difficulties to make ends meet (18.0 vs 13.6%). Globally, there were a greater proportion of women than of men whom they had: medical problems, cognitive problems, depression, and difficulties to carry out activities of the daily living. Overall, subjects that have had difficulties to make ends meet had greater prevalences of problems in all the dimensions of this evaluation. On the other hand, subjects that lived single had lower prevalences of problems in all the dimensions except they had a greater prevalence of depression. Conclusion. The multidimensional evaluation in elderly patients by the postal method is an efficient procedure that allows identifying many socioeconomic and health problems. In addition, it is feasible to identify to most fragile subjects and latter on to carry out preventive and curative interventions on them as well as to make their follow up