960 resultados para Factor de impacto
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Duración (en horas): Menos de 10 horas. Destinatario: Estudiante y Docente
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Background: Human melanoma frequently colonizes bone marrow (BM) since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC) microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2) in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown. Methods: Herein we analyzed the effect of cyclooxygenase-2 (COX-2) inhibitor celecoxib in a model of generalized BM dissemination of left cardiac ventricle-injected B16 melanoma (B16M) cells into healthy and bacterial endotoxin lipopolysaccharide (LPS)-pretreated mice to induce inflammation. In addition, B16M and human A375 melanoma (A375M) cells were exposed to conditioned media from basal and LPS-treated primary cultured murine and human BMSCs, and the contribution of COX-2 to the adhesion and proliferation of melanoma cells was also studied. Results: Mice given one single intravenous injection of LPS 6 hour prior to cancer cells significantly increased B16M metastasis in BM compared to untreated mice; however, administration of oral celecoxib reduced BM metastasis incidence and volume in healthy mice, and almost completely abrogated LPS-dependent melanoma metastases. In vitro, untreated and LPS-treated murine and human BMSC-conditioned medium (CM) increased VCAM-1-dependent BMSC adherence and proliferation of B16M and A375M cells, respectively, as compared to basal medium-treated melanoma cells. Addition of celecoxib to both B16M and A375M cells abolished adhesion and proliferation increments induced by BMSC-CM. TNF alpha and VEGF secretion increased in the supernatant of LPS-treated BMSCs; however, anti-VEGF neutralizing antibodies added to B16M and A375M cells prior to LPS-treated BMSC-CM resulted in a complete abrogation of both adhesion-and proliferation-stimulating effect of BMSC on melanoma cells. Conversely, recombinant VEGF increased adherence to BMSC and proliferation of both B16M and A375M cells, compared to basal medium-treated cells, while addition of celecoxib neutralized VEGF effects on melanoma. Recombinant TNFa induced B16M production of VEGF via COX-2-dependent mechanism. Moreover, exogenous PGE2 also increased B16M cell adhesion to immobilized recombinant VCAM-1. Conclusions: We demonstrate the contribution of VEGF-induced tumor COX-2 to the regulation of adhesion-and proliferation-stimulating effects of TNFa, from endotoxin-activated bone marrow stromal cells, on VLA-4-expressing
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Monografia (especialização) – Curso de Parlamento e Direito, Câmara dos Deputados, Centro de Formação, Treinamento e Aperfeiçoamento (Cefor), 2015.
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Background: The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE). A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results: Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE epsilon 4 allele, increasing the risk of AD (OR = 5.96, 95% CI 2.74-12.94, p < 0.001 and OR = 6.71, 95% CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women. In MCI patients such as synergistic effect was only found between AG and APOE epsilon 4 allele (OR = 3.21 95% CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95% CI 1.69-20.42, p < 0.01). Conclusion: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon 4 allele that proves greater in women with AD.
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[EN] Enforcement of rural policy measures within National Parks may have a particular importance as they may contribute to reach socioeconomic objectives devised for such areas. So this paper approaches as case study the application of a relevant rural development measure in the Northumberland National Park (NNP) –England, North East— over the period 2000-2008 in order to explore whether NNP makes any difference in terms of enforcing rural policy measures. The main research findings indicate that NNP may have some sort of positive impact on rural development, but support relying on tourism monoculture may be a background reason for undesired negative consequences.
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397 p.
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La mastectomía, ya sea debida a un cáncer de mama o realizada profilácticamente, es considerada por muchas mujeres como un ataque a su feminidad e identidad, causando en ellas un gran impacto psicosocial que comprometerá su calidad de vida. Por un lado, la mastectomía afecta negativamente a algunos aspectos de su autopercepción como son su imagen corporal o su sexualidad. Por otro lado, sus relaciones sociales pueden verse perjudicadas, pudiendo resultar en una ruptura con sus parejas o en el cese de sus relaciones sexuales incluso tras la reconstrucción. Ante estos problemas, la enfermera debe ayudar a la mujer a adaptarse a esta nueva situación a través de unos cuidados individualizados que favorezcan su auto-aceptación y promuevan la reestructuración social. Sin embargo, muchas enfermeras reconocen una falta de conocimiento y dificultades comunicativas a la hora de abordar estos temas, así como una escasez de medios para poder realizarlo. Por todo ello, parece evidente la necesidad de una formación específica al respecto.