Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.

DietPlan : Desenvolupament d’un assistent nutricional online

Avui en dia, Internet permet ampliar l'horitzó d'alguns serveis, donant-los un altre caire més versàtil i còmode pel client final. El fet de posar a disposició del client un servei com el de la dietètica i la nutrició 24 hores al dia i 7 dies a la setmana, sense que perdi el seu valor i continui sent individualitzat, ofereix al client un coaching en aquest terreny i, al negoci, una altra visió del mateix. Així doncs, el principal objectiu és desenvolupar un lloc web, on l'usuari final pugui rebre una valoració dietètica i nutricional del seu estat actual de manera automàtica i, a la vegada, se li aportin els punts on pot millorar i una dieta escaient. Tot i així, la figura del professional en dietètica participarà del procés, ja que sempre existiran casos més complicats que d'altres.

Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis.

BACKGROUND & AIMS: Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE) and to provide end points for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patient assessments of disease severity. We also evaluated relationships between patient assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS: We collected information from 186 patients with EoE in Switzerland and the United States (69.4% male; median age, 43 y) via surveys (n = 135), focus groups (n = 27), and semistructured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patient assessment of EoE severity. The PRO instrument was used prospectively in 153 adult patients with EoE (72.5% male; median age, 38 y), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 y). RESULTS: Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patient assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity (range, 0-10) and PRO score (range, 0-8.52) was 0.15. CONCLUSIONS: We developed and validated an EoE scoring system based on 7 PRO items that assess symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.

Oxygen content and inhomogeneity effects on the electrical properties of YBa2Cu3Oy thin films

Oxygen content is a very important factor influencing the electrical properties of YBa2Cu3Oy. In this work the electrical properties of laser deposited YBa2Cu3Oy thin films on LaAlO3(100), in the whole range 6 y 7, are studied. An electrical network model, which randomly assigns oxygen contents and R(T) characteristics to the different elements in the circuit according to an arbitrary distribution, is used to analyze several features in the measured R(T) characteristics as a function of oxygen homogeneity. The model takes into account both short-range and long-range oxygen inhomogeneities. Good agreement between estimated oxygen contents from x-ray diffraction data in our samples and the average oxygen contents used to reproduce their R(T) characteristics is found. The model points out that oxygen homogeneity is very important in order to get the best and reproducible properties, and for conduction and superconductivity analysis through the shape or derivatives of R(T) characteristics.

Libertad condicional : propuestas para aumentar su concesión

La libertad condicional es una institución cuya aplicación no se da con la frecuencia que debería para lograr una resocialización y reinserción adecuada. Para reducir las tasas de encarcelamiento y los costes que se derivan, así como para igualar las tasas de liberados condicionales en Cataluña con las del resto del Estado, se proponen posibles mejoras para la concesión del último grado penitenciario. Las propuestas se desarrollan a partir de una investigación empírica basada en una revisión exhaustiva de los informes de pronóstico de reinserción de la Junta de Tratamiento y las resoluciones del Fiscal de Vigilancia Penitenciaria.Se formularán propuestas generales y específicas. Las primeras estarán encabezadas a modificar el punitivismo de la sociedad y la implementación de la libertad condicional. Las segundas estarán orientadas a focalizar el último grado penitenciario también a internos con alto riesgo de reincidencia, siempre y cuando se les proporcione una intervención intensiva; a mejorar y tratar tanto los factores estáticos como los dinámicos –hábitos laborales, toxicomanías, apoyo familiar– para facilitar el acceso a la libertad condicional según los actuales requisitos; a concienciar sobre la importancia de satisfacer la responsabilidad civil y a seguir la línea del modelo de riesgo, necesidad y responsividad.ABSTRACTParole is an institution whose application does not occur as often as it should to achieve resocialization and reintegration adequately. To reduce incarceration rates and its costs, as well as to equalize Catalonia’s parole rates with the rest of the state, it is suggested possible improvements for the last grade prison’s granting. The proposals were developed from an empirical research based on the analysis of the Treatment Assembly’s forecast reports reintegration and the Fiscal’s resolutions.It will be formulated general and specific proposals. The first one will be led to modify society’s punitivity and parole’s implementation. The second one will be directed on focusing parole in high risk prison inmates, as long as they have an intensive intervention; on improving and treat both static and dynamic factors –work habits, addictions, family support– to facilitate the access on parole under the current requirements; on raising the importance of paying the civil liability and follow the principles of the model of risk, needs and responsivity.

On-line desorption of dried blood spots coupled to hydrophilic interaction/reversed-phase LC/MS/MS system for the simultaneous analysis of drugs and their polar metabolites.

An assay for the simultaneous analysis of pharmaceutical compounds and their metabolites from micro-whole blood samples (i.e. 5 microL) was developed using an on-line dried blood spot (on-line DBS) device coupled with hydrophilic interaction/reversed-phase (HILIC/RP) LC/MS/MS. Filter paper is directly integrated to the LC device using a homemade inox desorption cell. Without any sample pretreatment, analytes are desorbed from the paper towards an automated system of valves linking a zwitterionic-HILIC column to an RP C18 column. In the same run, the polar fraction is separated by the zwitterionic-HILIC column while the non-polar fraction is eluted on the RP C18. Both fractions are detected by IT-MS operating in full scan mode for the survey scan and in product ion mode for the dependant scan using an ESI source. The procedure was evaluated by the simultaneous qualitative analysis of four probes and their relative phase I and II metabolites spiked in whole blood. In addition, the method was successfully applied to the in vivo monitoring of buprenorphine metabolism after the administration of an intraperitoneal injection of 30 mg/kg on adult female Wistar rat.

The Role of Information in Contemporary Migration. More Sources but Less Informed

La migració internacional contemporània és integrada en un procés d'interconnexió global definit per les revolucions del transport i de les tecnologies de la informació i la comunicació. Una de les conseqüències d'aquesta interconnexió global és que les persones migrants tenen més capacitat per a processar informació tant abans com després de marxar. Aquests canvis podrien tenir implicacions inesperades per a la migració contemporània pel que fa a la capacitat de les persones migrants per a prendre decisions més informades, la reducció de la incertesa en contextos migratoris, el desdibuixament del concepte de distància o la decisió d'emigrar cap a llocs més llunyans. Aquesta recerca és important, ja que la manca de coneixement sobre aquesta qüestió podria contribuir a fer augmentar la distància entre els objectius de les polítiques de migració i els seus resultats. El paper que tenen els agents de la informació en els contextos migratoris també podria canviar. En aquest escenari, perquè les polítiques de migració siguin més efectives, s'haurà de tenir en compte la major capacitat de la població migrant de processar la informació i les fonts d'informació en què es confia. Aquest article demostra que l'equació més informació equival a més ben informat no es compleix sempre. Fins i tot en l'era de la informació, les fonts no fiables, les expectatives falses, la sobreinformació i els rumors encara són presents en els contextos migratoris. Tanmateix, defensem l'argument que aquests efectes no volguts es podrien reduir complint quatre requisits de la informació fiable: que sigui exhaustiva, que sigui rellevant, que s'hi confiï i que sigui actualitzada.

How Party Linkages Shape Austerity Politics: Clientelism and Fiscal Adjustment in Greece and Portugal during the Eurozone Crisis

Drawing on an analysis of austerity reforms in Greece and Portugal during the sovereign debt crisis from 2009 onwards, we show how the nature of the linkages between parties and citizens shapes party strategies of fiscal retrenchment. We argue that parties which rely to a greater extent on the selective distribution of state resources to mobilize electoral support (clientelistic linkages) are more reluctant to agree to fiscal retrenchment because their own electoral survival depends on their ability to control state budgets to reward clients. In Greece, where parties relied extensively on these clientelistic linkages, austerity reforms have been characterized by recurring conflicts and disagreements between the main parties, as well as a fundamental transformation of the party system. By contrast, in Portugal, where parties relied less on clientelistic strategies, austerity reforms have been more consensual because fiscal retrenchment challenged to a lesser extent the electoral base of the mainstream parties.

Estudio multidisciplinario del ecosistema manglar en la comunidad tradicional de Curral Velho : Análisis de los servicios ecosistémicos producidos por los manglares a partir de la percepción de la comunidad de Curral Velho

Existe un número elevado de sectores de la sociedad que identifican los beneficios ofrecidos por el ecosistema del manglar así como la interacción entre ellos y el bienestar humano. Aún así, los servicios ecosistémicos (ESs) ofrecidos por la naturaleza son poco visibles y reconocidos legislativamente. Se puede observar que el manglar es uno de los ecosistemas más productivos del planeta. Tienen gran importancia tanto económica, social, ambiental como cultural, pero en las últimas décadas se ha hecho más notable una degradación progresiva debida, en gran parte, a la cría de camarón en cautividad, la camaronicultura. Por esta causa, se observa que la legislación y las políticas que pretenden gestionar estos ecosistemas, no actúan en consecuencia al no imponer ciertas medidas necesarias para esta vital protección, ni considera la importancia de los ecosistemas para la vida de las comunidades tradicionales que dependen de sus servicios para sobrevivir. Por ello es necesario producir un conocimiento sobre ESs a partir de la percepción por parte de la comunidad y que la comunidad se implique en la resolución de esta problemática, ya sea en la toma de decisiones o mediante ciertas actividades o acciones que puedan denunciar estas prácticas insostenibles. Frente a este contexto, este trabajo fue realizado a partir de la información obtenida en la comunidad de Curral Velho (Ceará, Brasil), con el objetivo de realizar un estudio sobre los ESs proveídos por los manglares a partir de la percepción de la comunidad para demostrar la importancia que éstos tienen para el bienestar de los habitantes de la comunidad que se benefician. Los resultados fueron alcanzados a partir de una combinación de metodologías sociales que hacen posible la participación por parte de los habitantes: free listing, encuestas de valoración, grupos focales y observación participante. En la aplicación de estos métodos fueron identificados nuevos ESs de carácter psicológico por los pescadores/as de la pesca artesanal. Por lo que se concluye que es importante tener en cuenta la opinión de las comunidades adyacentes para preservar los flujos ecosistémicos que proporciona el manglar.

Association between polyclonal B cell activation and the presence of autoantibodies in mice infected with Yersinia enterocolitica O:3

Eight-week old conventional female Swiss mice were inoculated intravenously with Yersinia enterocolitica O:3. A second group of normal mice was used as control. Five mice from each group were bled by heart puncture and their spleens were removed for spleen cell collection on the 3rd, 5th, 7th, 10th, 14th and 21st day after infection. Immunoglobulin-secreting spleen cells were detected by the isotype-specific protein A plaque assay. Total immunoglobulin levels were determined in mouse serum by single radial immunodiffusion and the presence of autoantibodies was determined by ELISA. We observed a marked increase in the total number of cells secreting immunoglobulins of all isotypes as early as on the 3rd day post-infection and the peak of secretion occurred on the 7th day. At the peak of the immunoglobulin response, the total number of secreting cells was 19 times higher than that of control mice and most immunoglobulin-secreting cells were of the IgG2a isotype. On the 10th day post-infection, total serum immunoglobulin values were 2 times higher in infected animals when compared to the control group, and continued at this level up to the 21st day post-infection. Serum absorption with viable Y. enterocolitica cells had little effect on antibody levels detected by single radial immunodiffusion. Analysis of serum autoantibody levels revealed that Y. enterocolitica infection induced an increase of anti-myosin and anti-myelin immunoglobulins. The sera did not react with collagen. The present study demonstrates that Y. enterocolitica O:3 infection induces polyclonal activation of murine B cells which is correlated with the activation of some autoreactive lymphocyte clones

Comparative pathogenicity of Coxsackievirus A16 circulating and noncirculating strains in vitro and in a neonatal mouse model

An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 strain causes severe lesions in muscle and lung tissues. Therefore, an effective CV vaccine with improved pathogenic safety is needed. The aim of this study was to evaluate the in vivo safety and in vitro replication capability of a noncirculating CVA16 SHZH05 strain. The replication capacity of circulating CVA16 strains CC024, CC045, CC090 and CC163 and the noncirculating SHZH05 strain was evaluated by cytopathic effect in different cell lines. The replication capacity and pathogenicity of the CC024 and SHZH05 strains were also evaluated in a neonatal mouse model. Histopathological and viral load analyses demonstrated that the SHZH05 strain had an in vitro replication capacity comparable to the four CC strains. The CC024, but not the SHZH05 strain, became distributed in a variety of tissues and caused severe lesions and mortality in neonatal mice. The differences in replication capacity and in vivo pathogenicity of the CC024 and SHZH05 strains may result from differences in the nucleotide and amino acid sequences of viral functional polyproteins P1, P2 and P3. Our findings suggest that the noncirculating SHZH05 strain may be a safer CV vaccine candidate than the CC024 strain.

Aplicación de diversos métodos químicos para determinar actividad antioxidante en pulpa de frutos

El Brazil es considerado un de los principales países productores de zumos de frutos, ocupando en concreto la tercera posición respecto a esto. La diversidad de frutos en el mercado es cada vez mayor, introduciéndose diariamente nuevos frutos tropicales cuyas propiedades y actividades no están aún totalmente determinadas. El gobierno brasileño apoya el comercio exterior de frutos, invirtiendo fondos en exposiciones que promueven y sitúan a los nuevos productos en los países de la Unión Europea, tal como la "Brazilian Fruit Festival" que promociona frutos in natura, pulpas congeladas y zumos procesados. Se publican cada vez en mayor número nuevas investigaciones que asocian el consumo de frutas con efectos beneficiosos para la salud humana. Este trabajo tiene por objeto la determinación del índice de fenoles totales (FT), antocianos totales (AT) y la capacidad antioxidante de las pulpas de frutos comerciales congelados, aplicando los métodos espectrofotométrico químicos mas en boga para la determinación de la actividad antioxidante (ABTS, DPPH y DMPD). Se ha determinado la capacidad antioxidante de las pulpas de los frutos tropicales de mayor consumo en el mercado del sur de Brazil (mora, uva, açaí, guayaba, fresa, acerola, piña, mango, graviola, cupuaçu y maracuyá) aplicando el método ABTS con medidas a dos tiempos (1 y 7 minutos), DPPH (30 y 60 minutos) y DMPD (10 minutos). Los valores TEAC (capacidad antioxidante equivalente al Trolox) obtenidos de las pulpas oscilan entre mínimos y máximos de 2,0 y 67,2 µmol/g aplicando el ensayo ABTS, 1,02 y 67,0 µmol/g aplicando DPPH y 4,2 y 46,6 µmol/g aplicando DMPD. La capacidad antioxidante obtenida por los métodos ABTS y DPPH se encuentra correlacionada con el contenido de compuestos fenólicos y antocianos.

La ciudad de Dios

UANL