Adipocyte-specific Nos2 deletion improves insulin resistance and dyslipidemia through brown fat activation in diet-induced obese mice.

OBJECTIVE: Inducible nitric oxide (NO) synthase (NOS2) is a well-documented inflammatory mediator of insulin resistance in obesity. NOS2 expression is induced in both adipocytes and macrophages within adipose tissue during high-fat (HF)-induced obesity. METHODS: Eight-week-old male mice with adipocyte selective deletion of the Nos2 gene (Nos2AD-KO) and their wildtype littermates (Nos2fl/fl) were subjected to chow or high-fat high-sucrose (HFHS) diet for 10 weeks followed by metabolic phenotyping and determination of brown adipose tissue (BAT) thermogenesis. The direct impact of NO on BAT mitochondrial respiration was also assessed in brown adipocytes. RESULTS: HFHS-fed Nos2AD-KO mice had improved insulin sensitivity as compared to Nos2fl/fl littermates. Nos2AD-KO mice were also protected from HF-induced dyslipidemia and exhibited increased energy expenditure compared with Nos2fl/fl mice. This was linked to the activation of BAT in HFHS-fed Nos2AD-KO mice as shown by increased Ucp1 and Ucp2 gene expression and augmented respiratory capacity of BAT mitochondria. Furthermore, mitochondrial respiration was inhibited by NO, or upon cytokine-induced NOS2 activation, but improved by NOS2 inhibition in brown adipocytes. CONCLUSIONS: These results demonstrate the key role of adipocyte NOS2 in the development of obesity-linked insulin resistance and dyslipidemia, partly through NO-dependent inhibition of BAT mitochondrial bioenergetics.

Resveratrol inhibition of inducible nitric oxide synthase in skeletal muscle involves AMPK but not SIRT1.

The plant-derived polyphenol resveratrol (RSV) modulates life span and metabolism, and it is thought that these effects are largely mediated by activating the deacetylase enzyme SIRT1. However, RSV also activates the cell energy sensor AMP-activated protein kinase (AMPK). We have previously reported that AMPK activators inhibit inducible nitric oxide synthase (iNOS), a key proinflammatory mediator of insulin resistance in endotoxemia and obesity. The aim of this study was to evaluate whether RSV inhibits iNOS induction in insulin target tissues and to determine the role of SIRT1 and AMPK activation in this effect. We found that RSV (40 mg/kg ip) treatment decreased iNOS induction and NO production in skeletal muscle and white adipose tissue, but not in liver, of endotoxin (LPS)-challenged mice. This effect of the polyphenol was recapitulated in vitro, where RSV (10-80 µM) robustly inhibited iNOS protein induction and NO production in cytokine/LPS-treated L6 myocytes and 3T3-L1 adipocytes. However, no effect of RSV was observed on iNOS induction in FAO hepatocytes. Further studies using inhibitors of SIRT1 revealed that the deacetylase enzyme is not involved in RSV action on iNOS. In marked contrast, RSV activates AMPK in L6 myocytes, and blunting its activation using Compound C or RNA interference partly blocked the inhibitory effect of RSV on NO production. These results show that RSV specifically inhibits iNOS induction in muscle through a mechanism involving AMPK but not SIRT1 activation. This anti-inflammatory action of RSV likely contributes to the therapeutic effect of this plant polyphenol.

Activity of Adesmia boronioides resinous exudate against phytopathogenic bacteria.

Resinous exudate obtained from the aerial parts of Adesmia boronioides Hook.f. were evaluated to determine anti-phytopathogenic effects. Briefly, resinous exudate was obtained by dipping fresh plant material in dichloromethane; chemical composition was determined by GC-MS; and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated against four phytopathogenic bacteria. Resinous exudate yield was 8.5% (resin/fresh plant), of which esquel-6-en-9-one (14.25%), esquel-7-en-9-one (5.86%), and veratric acid (2.59%) were the effective antibacterial compounds. Tested against Pectobacterium carotovorum subsp. carotovora, Erwinia amylovora, Bacillus subtilis, and Pseudomonas syringae, MICs and MBCs ranged from 16 to 128 µg/mL and 32-256 µg/mL, respectively. These results provide initial evidence that resinous bush A. boronioides is a new and alternative source of substances with agricultural interest.

Actividad citotóxica de extractos crudos y fracciones de Blepharocalyx cruckshanksii contra líneas celulares de cáncer humano seleccionadas / Cytotoxic activity of crude extracts and fractions from Blepharocalyx cruckshanksii against selected human cancer cell lines

El presente estudio tiene como objetivo explorar las posibles aplicaciones de los extractos de corteza y hoja de Blepharocalyx cruckshanksii como agente citotóxico contra líneas celulares de cáncer in vitro ((MCF-7, PC-3 y HT-29) mediante el uso de ensayo de sulforhodamine B (SRB). El ensayo de citotoxicidad reveló que el extracto de acetato de etilo de la corteza exhibía una actividad anticancerígena marcada. El extracto activo se sometió a un reparto líquido-líquido usando hexano y acetato de etilo para obtener fracciones basadas en su polaridad. Sin embargo, la Fracción 4 (F4) fue identificado como el más efectivo de la serie al mostrar contra todas las líneas celulares de cáncer una citotoxicidad cercana a los agentes antineoplásicos ensayados. Luego, F4 se analizó por cromatografía de gasesespectrometría de masas (GC-MS) para identificar sus componentes principales y relacionar estos componentes con el efecto citotóxico. Los resultados obtenidos indicaron que la corteza de B. cruckshanksii tiene una excelente actividad citotóxica y amerita estudios adicionales para aislar nuevos compuestos para quimioterapia.

The present study aims to explore the potential applications of Blepharocalyx cruckshanksii bark and leaf extracts as a cytotoxic agent against in vitro cancer cell lines (MCF-7, PC-3 and HT-29) by using sulforhodamine B (SRB) assay. The cytotoxicity assay revealed that the ethyl acetate extract from the bark exhibited marked anticancer activity. The active extract was subjected to liquid-liquid partitioning by using hexane and ethyl acetate to obtain fractions based on their polarity. However, Fraction 4 (F4) was identified as the most effective of the series by displaying against all cancer cell lines a cytotoxicity close to antineoplastic agents assayed. Then, F4 was analyzed by gas chromatography­mass spectrometry (GC-MS) to identify their major components and to relate these components to the cytotoxic effect. The results obtained indicated that B. cruckshanksii bark have excellent cytotoxic activity and warrant further studies to isolate novel compounds for chemotherapeutic use.

Aceptabilidad, consumo y tolerancia del complemento alimentario "leche enriquecida" en niños beneficiarios del Programa Alimentario Nutricional Integral

Introducción: Una de las mayores dificultades de los programas de alimentación complementaria es determinar cuál es el alimento más adecuado para mejorar el aporte nutricional, que presente una buena tolerancia y bajo nivel de rechazo. En Paraguay, el Instituto Nacional de Alimentación y Nutrición dependiente del Ministerio de Salud Pública y Bienestar Social cuenta con un programa alimentario nutricional integral, que no disponía de ninguna evaluación previa de la aceptación de su producto alimentario. Objetivo: Describir la aceptabilidad, consumo y tolerancia del complemento alimentario "Leche Enriquecida" en niños beneficiarios del Programa Alimentario Nutricional Integral. Método: Estudio descriptivo, retrospectivo. Muestreo no probabilístico, por casos consecutivos. Incluyó a los padres y/o cuidadores de niños beneficiarios del Programa Alimentario Nutricional Integral (PANI) que acudieron a los servicios de salud de Concepción, Guaira y Caaguazú durante los años 2010 y 2011. La aceptabilidad del complemento alimentario se midió mediante una encuesta realizada a los padres y/o cuidadores de los niños participantes del estudio. Resultados: En el estudio participaron 86 padres y cuidadores de niños menores de cinco años de edad. 44/86 de las madres consideraron que al niño le gusta mucho el complemento alimentario, la mayor parte de los beneficiarios consumieron el complemento todos los días (n=75). 85/86 de la población estudiada no presentó intolerancia a la leche enriquecida. Conclusión: El complemento nutricional presenta una excelente aceptabilidad, consumo y tolerancia por parte de los beneficiarios.

Introduction: One of the major difficulties of complementary feeding programs is to determine which food is the most adequate to improve nutritional intake, which has a good tolerance and a low level of rejection. In Paraguay, the National Institute of Food and Nutrition under the Ministry of Public Health and Social Welfare has a comprehensive nutritional food program, this program has no evaluation of the acceptance of its food product. Objective: Describe the acceptability, consumption and tolerance of the enriched milk supplement in children beneficiaries of the Integral Nutritional Feeding Program. Method: A retrospective descriptive study that included parents and / or caregivers of children from the Integral Nutritional Food Program (PANI) who attended the health services of Concepción, Guaira and Caaguazú during the years 2010 and 2011. Not probabilistic consecutive sampling cases. The acceptability of the food supplement was measured by a survey of the parents and/or caregivers of the children participating in the study. Results: The study involved 86 children under five years of age. 44/86 of the mothers consider that the child is very fond of the food supplement, most of the recipients consumed the supplement every day (n=75). 85/86 of the population studied did not have complement intolerance. Conclusion: The nutritional supplement presents excellent acceptability, consumption and tolerance on the part of the beneficiaries.

Obese mice lacking inducible nitric oxide synthase are sensitized to the metabolic actions of peroxisome proliferator-activated receptor-gamma agonism.

OBJECTIVE: Synthetic ligands for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) improve insulin sensitivity in obesity, but it is still unclear whether inflammatory signals modulate their metabolic actions. In this study, we tested whether targeted disruption of inducible nitric oxide (NO) synthase (iNOS), a key inflammatory mediator in obesity, modulates the metabolic effects of rosiglitazone in obese mice. RESEARCH DESIGN AND METHODS: iNOS(-/-) and iNOS(+/+) were subjected to a high-fat diet or standard diet for 18 weeks and were then treated with rosiglitazone for 2 weeks. Whole-body insulin sensitivity and glucose tolerance were determined and metabolic tissues harvested to assess activation of insulin and AMP-activated protein kinase (AMPK) signaling pathways and the levels of inflammatory mediators. RESULTS: Rosiglitazone was found to similarly improve whole-body insulin sensitivity and insulin signaling to Akt/PKB in skeletal muscle of obese iNOS(-/-) and obese iNOS(+/+) mice. However, rosiglitazone further improved glucose tolerance and liver insulin signaling only in obese mice lacking iNOS. This genotype-specific effect of rosiglitazone on glucose tolerance was linked to a markedly increased ability of the drug to raise plasma adiponectin levels. Accordingly, rosiglitazone increased AMPK activation in muscle and liver only in obese iNOS(-/-) mice. PPAR-gamma transcriptional activity was increased in adipose tissue of iNOS(-/-) mice. Conversely, treatment of 3T3-L1 adipocytes with a NO donor blunted PPAR-gamma activity. CONCLUSIONS: Our results identify the iNOS/NO pathway as a critical modulator of PPAR-gamma activation and circulating adiponectin levels and show that invalidation of this key inflammatory mediator improves the efficacy of PPAR-gamma agonism in an animal model of obesity and insulin resistance.

Reincidencia y desistimiento en adolescentes infractores: análisis de trayectorias delictivas a partir de autorreporte de delitos, consumo de sustancias y juicio profesional / Recidivism and Desistance in Young Offenders: Criminal Trajectory Analysis from Self-Reported Offenses, Substance Use and Professional Judgment

Se analizan respuestas de 239 adolescentes varones condenados por diversos delitos, y agrupados en seis trayectorias delictivas definidas por características psicológicas, riesgos y comportamiento problemático. El autorreporte de delitos se obtiene con la Escala EDA; consumo problemático, con la Guía DEP-ADO, riesgos y recursos con el Inventario IRNC y la Ficha "FER-R" y delincuencia oficial desde los expedientes judiciales. El propósito fue caracterizar diferencialmente las trayectorias delictivas, analizando retrospectivamente la relación entre volumen de delitos autorreportados, consumo de sustancias, acumulación de factores de riesgo y recursos y sanciones. Los resultados muestran evoluciones distintas por trayectoria con diferente potencial de reincidencia y desistimiento, independientes de la sanción ejecutada. Se discute fundamentando la necesidad de programas de intervención diferenciada por trayectorias delictivas.

We analyzed responses of 239 male adolescents convicted of various crimes and offenses, grouped into six trajectories defined psychological characteristics, risks and problem behavior. The self-reporting of crimes is obtained with the "EDA" scale, problematic abuse with the "DEP-ADO" grid, risks and resources with "IRNC" inventory and the "FERR" grid, from official crime the court records. The purpose was to characterize differentially criminal trajectories, retrospectively, analyzing the relationship between self-reported crime volume, substance abuse, accumulation of risk factors and resources and penalties. The results show different trends for trajectories with diverse potential recidivism and desistance, independent of the penalty executed. We discuss basing the need for differentiated intervention programs criminal trajectories.