Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18

Background: Implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanisms. A hepatic melanoma metastasis model where a majority of metastases are generated via interleukin-18-dependent mechanisms was used to test whether anti-inflammatory properties of resveratrol can interfere with mechanisms of metastasis. Methods: Two experimental treatment schedules were used: 1) Mice received one daily oral dose of 1 mg/kg resveratrol after cancer cell injection and the metastasis number and volume were determined on day 12. 2) Mice received one daily oral dose of 1 mg/kg resveratrol along the 5 days prior to the injection of cancer cells and both interleukin-18 (IL-18) concentration in the hepatic blood and microvascular retention of luciferase-transfected B16M cells were determined on the 18(th) hour. In vitro, primary cultured hepatic sinusoidal endothelial cells were treated with B16M-conditioned medium to mimic their in vivo activation by tumor-derived factors and the effect of resveratrol on IL-18 secretion, on vascular cell adhesion molecule-1 (VCAM-1) expression and on tumor cell adhesion were studied. The effect of resveratrol on melanoma cell activation by IL-18 was also studied. Results: Resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion-and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells. Conclusions: These results demonstrate multiple sites for therapeutic intervention using resveratrol within the prometastatic microenvironment generated by tumor-induced hepatic IL-18, and suggest a remarkable effect of resveratrol in the prevention of inflammation-dependent melanoma metastasis in the liver.

Copia de cartas remitidas a los sacerdotes vascos presos por Alberto de Onaindia entre el 12 de enero y el 11 de mayo de 1940.

Fecha: 12-1/4-4/11-5-1940 (>1970 copia) / Unidad de instalación: Carpeta 45 - Expediente 2-13 / Nº de pág.: 20 (mecanografiadas)

The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event

6 p.

Clasificadores supervisados para predecir la abstinencia a 12 meses en fumadores tratados con vareniclina

Tesis leida dentro del Master de "Ingeniería Computacional y Sistemas Inteligentes"

Introducción a Gretl 1.9.12 para Econometría

Guía para el uso de Gretl en un curso introductorio de Econometría y/o análisis de datos

ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP

15 p.

Dynamics of Streptococcus pneumoniae Serotypes Causing Acute Otitis Media Isolated from Children with Spontaneous Middle-Ear Drainage over a 12-Year Period (1999–2010) in a Region of Northern Spain

10 p.

Evaluación de la incontinencia urinaria de esfuerzo en primigravidas a termino. Seguimiento a los 6, 12 y 24 meses postparto

pag. var.: il.

Effects of 12 weeks muscle hipetrophy training program in a young male athlete: stydy case

PURPOSE: The main goals of the present study were: 1) to review some recommendations about how to increase lean body mass; 2) to analyse whether following scientific sources of current recommendations, visible changes can be shown or not in a participant (body composition, strength and blood analyses). METHODS: One male athlete completed 12 weeks of resistance training program and following a diet protocol. Some test were determined such as, strength 6RM, blood analyses, skindfold measurements, body perimeters and impedance test. Body composition measurements were taken 3 times during the program (before-T1, after 6 weeks of intervention period-T2 and at the end of the program-T3). On the other hand, strength tests and blood analyses were performed twice (before and after the program). RESULTS: Strength was increased in general; blood analyses showed that Creatine kinase was increased a 104% and Triglycerides level was decreased a 22.5%; in the impedance test, body mass (1.6%), lean body mass (3.5%) and Body mass index (1.7%) were increased, whereas fat mass was decreased (15.5%); relaxed and contracted biceps perimeters were also increased. CONCLUSION: A muscle hypertrophy training program mixed with an appropriate diet during 12 weeks leads to interesting adaptations related to increase in body weight, lean body mass, biceps perimeters, strength and creatine kinase levels, and a decrease in fat mass.

Plan de mejora ante los resultados del análisis de los hábitos deportivos y el sedentarismo en estudiantes de 12-13 años de los centros escolares Lauro Ikastola, Colegio Miribilla y Txorierri Ikastetxea

El presente estudio es una investigación llevada a cabo con chicos y chicas de entre 12 y 13 años sobre los hábitos deportivos y el sedentarismo. El estudio se ha llevado a cabo en 3 centros escolares vizcaínos diferentes: Lauro Ikastola (Loiu), Txorierri ikastetxea (Derio) y Colegio Miribilla (Bilbao) con el fin de abarcar y analizar una mayor heterogeneidad de alumnos. Hoy en día el sedentarismo infantil es un factor de ri esgo muy importante entre los más jóvenes y por ello es de vital importancia trabajar y proponer una serie de acciones y estrategias para incentivar a los adolescentes a llevar una vida activa y saludable.

Etapa sentikorraren lehenengo fasearen (8-12 urte) garrantzia keinu teknikoak barneratzerako surfean

8-12 urte bitarteko umeen surf entrenamendu prozesua nola planifikatu behar da, murgilduta dauden etapa sentikorra kontuan hartuz.

Improved Mechanical Properties of Compatibilized Polypropylene/Polyamide-12 Blends

Compatibilized blends of polypropylene (PP) and polyamide-12 (PA12) as a second component were obtained by direct injection molding having first added 20% maleic anhydride-modified copolymer (PP-g-MA) to the PP, which produced partially grafted PP (gPP). A nucleating effect of the PA12 took place on the cooling crystallization of the gPP, and a second crystallization peak of the gPP appeared in the PA12-rich blends, indicating changes in the crystalline morphology. There was a slight drop in the PA12 crystallinity of the compatible blends, whereas the crystallinity of the gPP increased significantly in the PA12-rich blends. The overall reduction in the dispersed phase particle size together with the clear increase in ductility when gPP was used instead of PP proved that compatibilization occurred. Young's modulus of the blends showed synergistic behavior. This is proposed to be both due to a change in the crystalline morphology of the blends on the one hand and, on the other, in the PA12-rich blends, to the clear increase in the crystallinity of the gPP phase, which may, in turn, have been responsible for the increase in its continuity and its contribution to the modulus.

Cytokine pathway disruption in a mouse model of schizophrenia induced by Munc18-1a overexpression in the brain

Background: An accumulating body of evidence points to the significance of neuroinflammation and immunogenetics in schizophrenia, and an imbalance of cytokines in the central nervous system (CNS) has been suggested to be associated with the disorder. Munc18-overexpressing mice (Munc18-OE) have provided a model for the study of the alterations that may underlie the symptoms of subjects with schizophrenia. The aim of the present study was to elucidate the involvement of neuroinflammation and cytokine imbalance in this model. Methods: Cytokines were evaluated in the cortex and the striatum of Munc18-OE and wild-type (WT) mice by enzyme-linked immunosorbent assay (ELISA). Protein levels of specific microglia and macrophage, astrocytic and neuroinflammation markers were quantified by western blot in the cortex and the striatum of Munc18-OE and WT mice. Results: Each cytokine evaluated (Interferon-gamma (IFN-gamma), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-2 (IL-2) and CCL2 chemokine) was present at higher levels in the striatum of Munc18-OE mice than WT. Cortical TNF-alpha and IL-2 levels were significantly lower in Munc18-OE mice than WT mice. The microglia and macrophage marker CD11b was lower in the cortexes of Munc18-OE mice than WT, but no differences were observed in the striatum. Glial Fibrillary Acidic Protein (GFAP) and Nuclear Factor-kappaB (NF-kappa B)p65 levels were not different between the groups. Interleukin-1beta (IL-1 beta) and IL-6 levels were beneath detection limits. Conclusions: The disrupted levels of cytokines detected in the brain of Munc18-OE mice was found to be similar to clinical reports and endorses study of this type for analysis of this aspect of the disorder. The lower CD11b expression in the cortex but not in the striatum of the Munc18-OE mice may reflect differences in physiological activity. The cytokine expression pattern observed in Munc18-OE mice is similar to a previously published model of schizophrenia caused by maternal immune activation. Together, these data suggest a possible role for an immune imbalance in this disorder.