Optimización por los alumnos de Fisioterapia de los recursos bibliográficos existentes en la biblioteca del cento y aplicación a la docencia de Fisiología del ejercicio. Potenciación del uso del inglés científico

Memoria ID-145. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2010-2011.Durante el desarrollo de Proyecto previo en el curso 2009-10 detectamos dos puntos débiles fundamentales en la formación de los estudiantes y susceptibles de mejora ya que inciden directamente en dos deficiencias detectadas por los empleadores en los alumnos egresados de los planes de estudio anteriores (1995 y 2001), y que están recogidas en el Informe de Autoevaluación de la Diplomatura de Fisioterapia realizado durante el curso 2004-05 y publicado en marzo del 2005. Dichas deficiencias son: 1) la escasa autonomía de los egresados en la búsqueda de medios o información para resolver problemas, y 2) la baja comprensión y escaso uso del inglés en el ámbio laboral. Por ello, nos propusimos dos objetivos concretos para mejorar ambas competencias transversales

Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy

This is an open access article distributed under the Creative Commons Attribution License.Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.This study was supported by grants from Ministerio de Economía y Competitividad (Grant SAF2010-15881 and Red de Investigacion Cooperativa en Enfermedades Renales REDINREN RD12/0021/0032), Junta de Castilla y León (Grant SA 001/C05 and Excellence Group GR100), and REDINREN which is an initiative of the Instituto de Salud Carlos III of Spain supported by FEDER funds. When performing the present study, Ana B. Rodríguez-Pena was a fellow of the Fundacion Renal “Iñigo Ávarez de Toledo” and Neil G. Docherty was a fellow ofThe Marie Curie Programme, EU.Peer Reviewe

Experiencia docente para la implantación de nuevas metodologías activas de aprendizaje en la asignatura de fisiología para primer curso de fisioterapia

Memoria ID-0168. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2009-2010.En el curso 2010‐11 se implantarán los nuevos planes de estudio adaptados al EEES conducentes a la obtención del Título de Graduado/a en Fisioterapia. Conscientes de la importancia de concienciar a los estudiantes pertenecientes a esta última promoción del plan antiguo 2001 de los cambios metodológicos y modificaciones que supone la entrada en vigor del proceso de Bolonia para los fisioterapeutas, diseñamos este proyecto en el que se propone una estrategia docente basada en los principios que sustentan el proceso de adaptación de los futuros profesionales a las demandas de la sociedad propugnado en el EEES. Otras universidades de España ya han implantado estos nuevos planes para Fisioterapia durante este curso académico 2009/10. Para conseguir los objetivos de formación en competencias propias de la materia así como los de formación en competencias transversales, se emplean las técnicas docentes clásicas (clases magistrales, clases prácticas, seminarios y tutorías) pero con un enfoque mucho más activo y participativo, y se desarrollan otras técnicas como la elaboración de trabajos dirigidos mediante tutorías específicas para este propósito y la celebración de varios seminarios de diverso contenido

Reduced tumor growth and angiogenesis en endoglin-haploinsufficient mice

8 páginasEndoglin is a transforming growth factor-β1 (TGF-β1) accessory receptor which is highly expressed in tumor vessels. To study the role of endoglin in tumor growth and angiogenesis we induced a highly vascularized tumor in mice heterozygous for endoglin (Eng+/–) and in their control littermates (Eng+/+) by injecting 106 Lewis lung carcinoma (3LL) cells subcutaneously. Nine days after injection, the tumor was removed and weighed. Capillary density (CD31 immunohistochemistry), hemoglobin content and vascular cell adhesion molecule-1 (VCAM-1) expression were used to assess tumor vascularization. Tumor perfusion rate was measured by laser-Doppler technique. Expression of the hypoxia-inducible factor (HIF), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were determined by Western blot analysis. The aerobic metabolism and oxygen dependency were inferred from the measurement of ATP in tumoral tissue. Tumor weight, capillary density, hemoglobin and VCAM-1 were reduced by about 30% in Eng+/– compared to Eng+/+ littermates. The protein levels of eNOS and phosphorylated eNOS were significantly reduced in Eng+/– compared to Eng+/+ mice. HIF expression was slightly reduced whereas VEGF level was slightly increased in Eng+/– compared to Eng+/+. Tumor tissue levels of ATP and ADP were similar in both types of mice. These data demonstrate that endoglin plays a major role in tumor neoangiogenesisPeer reviewe

Activation of Erk1/2 and Akt following unilateral ureteral obstruction

Chronic unilateral ureteral obstruction is a well characterized model of renal injury leading to tubulointerstitial fibrosis and distinct patterns of cell proliferation and apoptosis in the obstructed kidney. In this study we assessed the contribution of the mitogen activated protein kinase (MAPK)-ERK1/2 and the phosphatidylinositol 3 kinase (PI3K)-Akt pathways to early renal changes following unilateral obstruction. Increased activation of small Ras GTPase and its downstream effectors ERK1/2 and Akt was detected in ligated kidneys. The use of specific pharmacological inhibitors to either ERK1/2 or Akt activation led to decreased levels of fibroblast-myofibroblast markers in the interstitium while inhibition of PI3K reduced the number of proliferating cells and the amount of interstitial extracellular matrix deposition. Treatment with an ERK1/2 inhibitor diminished the number of apoptotic tubule and interstitial cells. Our results suggest a role for the MAPK-ERK1/2 and PI3K-Akt systems in early changes induced by ureteral obstruction and that inhibition of these signaling pathways may provide a novel approach to prevent progression of renal fibrosis

Characterization of murine S-endoglin isoform and its effects on tumor development

12 páginas, 6 figuras, 2 tablas -- PAGS nros. 4450-4461Endoglin is a transmembrane glycoprotein that acts as an auxiliary receptor for transforming growth factor- (TGF-) and modulates cellular responses to this pleiotropic cytokine. Endoglin is strongly expressed in endothelial cells, where it appears to exert a crucial role in vascular development and angiogenesis. Two endoglin isoforms (L and S), differing in their cytoplasmic domains, have been previously characterized in human tissues. We now demonstrate the existence of similar L- and S-endoglin variants in murine tissues with 47 and 35 amino acids, respectively, in their cytoplasmic tail. RT–PCR analysis showed that L is the predominant endoglin isoform expressed in mouse tissues, although S-endoglin mRNA is significantly expressed in liver and lung, as well as in endothelial cell lines. Furthermore, a protein of size equivalent to recombinant S-endoglin expressed in mammalian cells was detected in mouse endothelial cells by Western blot analysis. L- and S-endoglin isoforms can form disulfide-linked heterodimers, as demonstrated by cotransfection of L- and S-endoglin constructs. To address the role of S-endoglin in vivo, an S-Eng+ transgenic mouse model that targets S-endoglin expression to the endothelium was generated. The lethal phenotype of endoglin-null (Eng-/-) mice was not rescued by breeding S-Eng+ transgenic mice into the endoglin-null background. S-Eng+ mice exhibited reduced tumor growth and neovascularization after transplantation of Lewis lung carcinoma cells. In addition, S-Eng+ mice showed a drastic inhibition of benign papilloma formation when subjected to two-stage chemical skin carcinogenesis. These results point to S-endoglin as an antiangiogenic molecule, in contrast to L-endoglin which is proangiogenicWe thank Sebastián Aliño, Benilde Jiménez and Amparo Cano for their generous gifts of cell lines. We also thank Annette Düwell for helping with mouse breeding and genotyping, and Cristina González for skilful technical assistance. This work was supported by grants from 'Ministerio de Educación y Ciencia (SAF2004-04902 to MQ, SAF2004-01390 to CB and BFU2004-00285-BFI to JML-N), 'Fondo de Investigación Sanitaria' (ISCIII, Red de Centros de Cáncer RTICCC (C03/10) to MQ and PI020200 to CB). EP-G was the recipient of a predoctoral fellowship from the 'Communidad Autónoma de Madrid"Peer reviewe

Absence of K-Ras reduces proliferation and migration but increases extracellular matrix synthesis in fibroblasts

The involvement of Ras-GTPases in the development of renal fibrosis has been addressed in the last decade. We have previously shown that H- and N-Ras isoforms participate in the regulation of fibrosis. Herein, we assessed the role of K-Ras in cellular processes involved in the development of fibrosis: proliferation, migration, and extracellular matrix (ECM) proteins synthesis. K-Ras knockout (KO) mouse embryonic fibroblasts (K-ras) stimulated with transforming growth factor-β1 (TGF-β1) exhibited reduced proliferation and impaired mobility than wild-type fibroblasts. Moreover, an increase on ECM production was observed in K-Ras KO fibroblasts in basal conditions. The absence of K-Ras was accompanied by reduced Ras activation and ERK phosphorylation, and increased AKT phosphorylation, but no differences were observed in TGF-β1-induced Smad signaling. The MEK inhibitor U0126 decreased cell proliferation independently of the presence of K-ras but reduced migration and ECM proteins expression only in wild-type fibroblasts, while the PI3K-AKT inhibitor LY294002 decreased cell proliferation, migration, and ECM synthesis in both types of fibroblasts. Thus, our data unveil that K-Ras and its downstream effector pathways distinctively regulate key biological processes in the development of fibrosis. Moreover, we show that K-Ras may be a crucial mediator in TGF-β1-mediated effects in this cell type.This work was supported by grants from Instituto de Salud Carlos III (PS09/01067, PI12/00959, co-funded by FEDER, and Retic RD06/0016/013 RedinRen) Spanish Ministry of Science and Innovation (BFU2008-01728 and SAF2013-45784-R) and Junta de Castilla y Leon (GRS167/A/07, IES095U14 and Excellence Group GR100). JMMF is supported by Junta de Castilla y Leon and European Social Fund.Peer Reviewe