Mejoras Operativas y Técnicas del VAMTAC ST5

Existe una gran variedad de vehículos en el ET, necesarios para la realización de las actividades y cometidos de las diferentes Unidades del ET, es por ello que constituyen un pilar importante en las Unidades. Entre los distintos vehículos existe el URO VAMTAC, de fabricación española. Este vehículo es muy utilizado en diferentes Unidades del Ejército de Tierra, como es en el Regimiento de Infantería “Garellano” 45. El VAMTAC tiene diferentes modelos, como es el S3 y el ST5, los cuales están siendo utilizados en el Batallón “Guipúzcoa” I/45. Son vehículos de alta movilidad, con una alta capacidad de transporte de material, así como la capacidad de acoplar diferentes armas de diferente calibre a su afuste. Es un vehículo de gran versatilidad y capacidad de reacción, que permite a este Bón, como aquellos que lo utilizan, una alta operatividad. Sin embargo, esta operatividad se ve afectada por los diferentes fallos de diseño que arrastra el modelo. Pues tras diferentes encuestas realizadas a personal de las Compañías del Batallón, acompañado de entrevistas a personal de segundo escalón, así como personal especializado, se han descubierto diferentes carencias de este vehículo que pueden ser solucionadas, mejorando así su eficacia y disminuyendo su tiempo en el taller esperando ser reparado.Estos problemas que se revelaron a través de las encuestas y entrevistas, y, tras un exhaustivo estudio, se centraron en las ruedas del vehículo. Estos problemas radicaban en una rotura de pernos, que venía provocada por diferentes factores, (material, tamaño, disposición,…), y en un desgaste de los elementos de freno. Las soluciones planteadas, tras su análisis, consisten en cambiar diferentes elementos de la rueda (llanta, disco de amarre y perno) y; proponer un nuevo diseño de los elementos de freno (pastilla de freno y disco de freno).Tras presentar los nuevos diseños y propuestas de mejoras se realizó un estudio de su viabilidad técnica y económica. Todo lo explicado anteriormente ayudado de las diferentes herramientas aprendidas en el grado como el análisis de riesgos, matriz DAFO, análisis de stakeholders y consultar bibliografía especializada.<br /

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

Role of inflammation in túbulo-interstitial damage associated to obstructive nephropathy

<p>Abstract</p> <p>Obstructive nephropathy is characterized by an inflammatory state in the kidney, that is promoted by cytokines and growth factors produced by damaged tubular cells, infiltrated macrophages and accumulated myofibroblasts. This inflammatory state contributes to tubular atrophy and interstitial fibrosis characteristic of obstructive nephropathy. Accumulation of leukocytes, especially macrophages and T lymphocytes, in the renal interstitium is strongly associated to the progression of renal injury. Proinflammatory cytokines, NF-κB activation, adhesion molecules, chemokines, growth factors, NO and oxidative stress contribute in different ways to progressive renal damage induced by obstructive nephropathy, as they induce leukocytes recruitment, tubular cell apoptosis and interstitial fibrosis. Increased angiotensin II production, increased oxidative stress and high levels of proinflammatory cytokines contribute to NF-κB activation which in turn induce the expression of adhesion molecules and chemokines responsible for leukocyte recruitment and iNOS and cytokines overexpression, which aggravates the inflammatory response in the damaged kidney. In this manuscript we revise the different events and regulatory mechanisms involved in inflammation associated to obstructive nephropathy.</p

Membrane and soluble forms of endoglin in preeclampsia

29 p.-4 fig.Preeclampsia is a disease of high incidence in pregnant women which complicates pregnancy and may lead to the death of mother and baby. Preeclampsia is characterized by a series of clinical features such as hypertension and proteinuria associated with endothelial dysfunction. Although the causes of disease have not been elucidated, it has been reported that high levels of endoglin, a TGF-beta auxiliary co-receptor, and a soluble form of this protein, occur respectively in the placenta and plasma of women who develop the disease. In this review, the alterations in vasculogenesis and angiogenesis that occur during preeclampsia, the cellular and molecular mechanisms that lead to increased membrane bound endoglin expression and soluble endoglin release, including hypoxia and oxidative stress, and the possible pathogenic role of soluble endoglin in this disease have been analyzed.Studies from the authors´ laboratories have been supported by grants from Ministerio de Ciencia e Innovación of Spain (SAF2010-19222 to CB; and SAF2010-15881 to JML-N), Genoma España (MEICA, to CB), Junta de Castilla y Leon (Grant GR100 to JMLN), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, to CB) and Red de Investigación Cooperativa en Enfermedades Renales (REDINREN RD012/0021, to JML-N). CIBERER and REDINREN are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain supported by FEDER funds. BO is supported by a fellowship from Ministry of Science and Innovation (BES-2008-005550).Peer reviewe

Endoglin regulates renal ischaemia-reperfusion injury

14 páginas, 10 figuras -- PAGS nros. 2106-2119Background. Renal ischaemia–reperfusion (I–R) can cause acute tubular necrosis and chronic renal deterioration. Endoglin, an accessory receptor for Transforming Growth Factor-β1 (TGF-β1), is expressed on activated endothelium during macrophage maturation and implicated in the control of fibrosis, angiogenesis and inflammation. Methods. Endoglin expression was monitored over 14 days after renal I–R in rats. As endoglin-null mice are not viable, the role of endoglin in I–R was studied by comparing renal I–R injury in haploinsufficient mice (Eng+/−) and their wild-type littermates (Eng+/+). Renal function, morphology and molecular markers of acute renal injury and inflammation were compared. Results. Endoglin mRNA up-regulation in the post-ischaemic kidneys of rats occurred at 12 h after I–R; endoglin protein levels were elevated throughout the study period. Expression was initially localized to the vascular endothelium, then extended to fibrotic and inflamed areas of the interstitium.  Two days after I–R, plasma creatinine elevation and acute tubular necrosis were less marked in Eng+/− than in Eng+/+ mice. Significant up-regulation of endoglin protein was found only in the post-ischaemic kidneys of Eng+/+ mice and coincided with an increased mRNA expression of the TGF-β1 and collagen IV (α1) chain genes. Significant increases in vascular cell adhesion molecule-1 (VCAM-1) and inducible nitric oxide synthase (iNOS) expression, nitrosative stress, myeloperoxidase activity and CD68 staining for macrophages were evident in post-ischaemic kidneys of Eng+/+, but not Eng+/− mice, suggesting that impaired endothelial activation and macrophage maturation may account for the reduced injury in post-ischaemic kidneys of Eng+/− mice. Conclusions. Endoglin is up-regulated in the post-ischaemic kidney and endoglin-haploinsufficient mice are protected from renal I–R injury. Endoglin may play a primary role in promoting inflammatory responses following renal I–R.This study was supported by grants from Ministerio de Ciencia y Tecnología (SAF2001-1701) and Junta de Castilla y León (SA22/03)Peer reviewe

Endoglin increases eNOS expression by modulating Smad2 protein levels and Smad2-dependent signalling

13 páginas, 8 figuras -- PAGS nros. 456-468The endothelial nitric oxide synthase (eNOS) is a critical regulator of cardiovascular homeostasis, whose dysregulation leads to different vascular pathologies. Endoglin is a component of the transforming growth factor beta (TGF-β) receptor complex present in endothelial cells that is involved in angiogenesis, cardiovascular development, and vascular homeostasis. Haploinsufficient expression of endoglin has been shown to downregulate endothelium-derived nitric oxide in endoglin+/− (Eng+/−) mice and cultured endothelial cells. Here, we find that TGF-β1 leads to an increased vasodilatation in Eng+/+ mice that is severely impaired in Eng+/− mice, suggesting the involvement of endoglin in the TGF-β regulated vascular homeostasis. The endoglin-dependent induction of eNOS occurs at the transcriptional level and is mediated by the type I TGF-β receptor ALK5 and its downstream substrate Smad2. In addition, Smad2-specific signaling is upregulated in endoglin-induced endothelial cells, whereas it is downregulated upon endoglin gene suppression with small interference RNA (siRNA). The endoglin-dependent upregulation of Smad2 was confirmed using eNOS and pARE promoters, whose activities are known to be Smad2 dependent, as well as with the interference of Smad2 with siRNA, Smurf2, or a dominant negative form of Smad2. Furthermore, increased expression of endoglin in endoglin-inducible endothelial cells or in transfectants resulted in increased levels of Smad2 protein without affecting the levels of Smad2 mRNA. The increased levels of Smad2 appear to be due to a decreased ubiquitination and proteasome-dependent degradation leading to stabilization of Smad2. These results suggest that endoglin enhances Smad2 protein levels potentiating TGF-β signaling, and leading to an increased eNOS expression in endothelial cells. J. Cell. Physiol. 210: 456–468, 2007. © 2006 Wiley-Liss, Inc.ALK, activin receptor-like kinase; Dox, doxycycline; eNOS, endothelial nitric oxide synthase; MEFs, murine embryonic fibroblasts; Pp, perfusion pressure; siRNA, small interference RNA; TGF-β, transforming growth factor-β; TβRI, TGF-β type I receptor; TβRII, TGF-β type II receptor; HHT, hereditary hemorrhagic telangiectasia. The endothelial nitric oxide synthase (eNOS or NOS3) is a critical regulator of cardiovascular homeostasis, vascular remodeling, and angiogenesis, and whose dysregulation leads to different types of vascular pathology (Kawashima and Yokoyama, 2004; Sessa, 2004; Tai et al., 2004). eNOS-derived NO is an endogenous vasodilatory molecule that regulates the tone of blood vessels and maintains an anti-thrombotic, anti-proliferative, and anti-apoptotic environment in the vessel wall (Sessa, 2004). Elucidation of the mechanisms and factors determining the expression and activity of eNOS under different physiological and pathophysiological conditions has long been considered central in order to understand the alterations in vascular NO production (Tai et al., 2004). The expression of eNOS is regulated by extracellular stimuli such as shear stress, estrogens, hypoxia, or growth factors (Davis et al., 2001; Simoncini et al., 2002; Tai et al., 2004). Among these, TGF-β1 has been shown to increase bovine aortic endothelial cell (BAEC) and human umbilical vein endothelial cell (HUVEC) steady-state eNOS mRNA expression (Inoue et al., 1995). Interestingly, eNOS expression is modulated not only by transcriptional, but also by post-transcriptional mechanisms (Sessa, 2004; Tai et al., 2004). At the transcriptional level, the eNOS promoter lacks a TATA box, but exhibits proximal elements such as Sp1 and GATA motifs, which are common characteristics of constitutively expressed genes (Zhang et al., 1995; Tai et al., 2004). The 5′-flanking region also contains many putative sites for further transcriptional regulation of eNOS. However, only a few of these sites have been formally shown to regulate eNOS transcription, including PEA3 (Cieslik et al., 1998) and AP-1 binding sites (Navarro-Antolin et al., 2000). Also, a region of the eNOS promoter extending from −1269 and −935 that contains Smad binding sites and mediates TGF-β induction of eNOS transcription, has been identified (Saura et al.,2002)Endoglin (CD105), is a 180-kDa homodimeric membrane glycoprotein which is strongly expressed by human endothelial cells and is involved in angiogenesis, cardiovascular development, and vascular homeostasis (Gougos and Letarte, 1990; Duff et al., 2003; Lebrin et al., 2005). The gene encoding endoglin has been identified as the target for the dominant vascular disorder known as hereditary hemorrhagic telangiectasia type 1 (HHT1) (Guttmacher et al., 1995). HHT is a highly penetrant autosomal dominant vascular dysplasia associated with frequent epistaxis, gastrointestinal bleedings, telangiectases, and arteriovenous malformations in brain, lung, and liver (Shovlin and Letarte, 1999; Marchuk and Lux, 2001). The mechanistic role of endoglin in angiogenesis and vascular remodeling is not known, but it is likely related to the transforming growth factor-β (TGF-β) system, as endoglin is a functional component of the membrane TGF-β receptor complex (Lastres et al., 1996) and is a substrate for TGF-β receptor-mediated phosphorylation (Guerrero-Esteo et al., 2002; Koleva et al., 2006). Signaling induction by TGF-β and related members of this superfamily regulate a variety of human diseases including cancer, fibrosis, developmental disorders, or cardiovascular pathology (Blobe et al., 2000; Siegel and Massague, 2003; Waite and Eng, 2003; Lebrin et al., 2005). TGF-β signaling is initiated when ligand induces formation of heteromeric complexes of type I and type II serine/threonine kinase receptors (TβRI and TβRII, respectively), which in turn activate and induce translocation of the Smad family of proteins to the nucleus (Attisano and Wrana, 2002; Miyazawa et al., 2002; Shi and Massague, 2003; Feng and Derynck, 2005). The association of endoglin with TβRII and TβRI (ALK1 and ALK5) regulates Smad signaling and cellular responses to TGF-β (Lastres et al., 1996; Letamendia et al., 1998; Li et al., 2000; Guerrero-Esteo et al., 2002). Endoglin regulates signal transduction of TGF-β1 by potentiating ALK1/Smad1 pathway and repressing the ALK5/Smad3 (Lebrin et al., 2004; Blanco et al., 2005), whereas it enhances ALK5/Smad2 signaling (Guerrero-Esteo et al., 2002). Conversely, in endoglin-deficient mice it has been shown that TGF-β/ALK5 signaling from endothelial cells to adjacent mesothelial cells is defective, as evidenced by reduced phosphorylation of Smad2 (Carvalho et al., 2004).Recently, it has been shown that endoglin regulates nitric oxide-dependent vasodilatation, as well as eNOS expression and activity (Jerkic et al., 2004; Toporsian et al., 2005). In addition, eNOS derived NO seems to play a major role in endoglin-dependent angiogenesis (Jerkic et al., 2006a) and COX-2 regulated expression (Jerkic et al., 2006b). The role of endoglin in the control of vascular tone was examined by measuring NO-dependent vasodilation in haploinsufficient mice (Eng+/−) and their Eng+/+ littermates (Jerkic et al., 2004). Urinary and plasma concentrations of nitrites were lower in Eng+/− than in Eng+/+ mice. The levels of eNOS in kidneys and femoral arteries were about half in Eng+/− than in Eng+/+ mice and were also reduced in primary cultures of aortic endothelial cells from Eng+/− compared with those from Eng+/+ mice. Furthermore, overexpression or suppression of endoglin in cultured cells induced a marked increase or decrease in the protein levels of eNOS, respectively (Jerkic et al., 2004). However, the mechanisms by which endoglin regulates eNOS expression are poorly understood. In the present work we show that endoglin enhances eNOS expression by increasing Smad2 protein levels and thereby enhancing TGF-β-dependent induction of eNOS in endothelial cellsThis work was supported by Ministerio de Educacion y Ciencia, Spain; grant numbers: SAF2004-01390 to C.B. and BFU2004-00285/BFI to J.M.L.-N.; Fondo de Investigaciœn Sanitaria, Spain; grant number: PI020200 to C.B.; COBRE Program, National Center for Research Resources, NIH, USA; grant number: P20-RR15555 to C.P.H.V.; Fondo Nacional de Ciencia y Tecnologia, Chile; grant number: FONDECYT-1050476 to J.F.S.; HHT Foundation International, Inc.; grant number: 3 to C.B.; Canadian Institute of Health Research (CIHR) to L.A.Peer reviewe

Endoglin regulates nitric oxide-dependent vasodilatation

23 p.-8 fig.Endoglin is a membrane glycoprotein that plays an important role in cardiovascular development and angiogenesis. We examined the role of endoglin in the control of vascular tone by measuring nitric oxide (NO)-dependent vasodilation in haploinsufficient mice (Eng(+/-)) and their Eng(+/+) littermates. The vasodilatory effect of acetylcholine, bradykinin, and sodium nitroprusside was assessed in anesthetized mice; in isolated, perfused hindlimbs; and in aortic rings. The substantial hypotensive and vasodilatory response induced by acetylcholine and bradykinin in Eng(+/+) was markedly reduced in Eng(+/-) mice. Both kinds of animals had similar responses to sodium nitroprusside, suggesting that the deficient vasodilatory effect is not due to a NO response impairment. Urinary and plasma concentrations of nitrites, a NO metabolite, were lower in Eng(+/-) than in Eng(+/+) mice. The levels of endothelial nitric oxide synthase (eNOS) in kidneys and femoral arteries were about half in Eng(+/-) than in Eng(+/+) mice and were also reduced in primary cultures of aortic endothelial cells from Eng(+/-) compared with those from Eng(+/+) mice. Furthermore, overexpression or suppression of endoglin in cultured cells induced a marked increase or decrease in the protein levels of eNOS, respectively. Thus, our results in vivo and in vitro demonstrate a relationship between endoglin and NO-dependent vasodilation mediated by the regulation of eNOS expression.This study was supported by grants from Comisión Interministerial de Ciencia y Tecnología(SAF2001/1701 to J. M. López-Novoa and SAF2000-0132 to C. Bernabéu); Comunidad Autónoma de Madrid (to C. Bernabéu); and Fondo de Investigación Sanitaria (PI020200 to C.Bernabéu). Dr. M. Jerkic is supported by a Visiting Professor Tenure of the Spanish Ministerio de Ciencia y Tecnología.Peer reviewe

Circulating soluble endoglin modifies the inflammatory response in mice

<div><p>Inflammation is associated with every health condition, and is an important component of many pathologies such as cardiovascular diseases. Circulating levels of soluble endoglin have been shown to be higher in the serum of patients with cardiovascular diseases with a significant inflammatory component. The aim of this study was to evaluate the implication of circulating soluble endoglin in the inflammatory response. For this purpose, a transgenic mouse expressing human soluble endoglin (sEng+) was employed, and three different inflammatory approaches were used to mimic inflammatory conditions in different tissues. This study shows that control sEng+ mice have a normal inflammatory state. The lung and kidney injury induced by the inflammatory agents was reduced in sEng+ mice, especially the intra-alveolar and kidney infiltrates, suggesting a possible reduction in inflammation induced by soluble endoglin. To deepen into this possible effect, the leukocyte number in the bronchoalveolar lavage and <i>air pouch</i> lavage was evaluated and a significant reduction of neutrophil infiltration in LPS-treated lungs and ischemic kidneys from sEng+ with respect to WT mice was observed. Additionally, the mechanisms through which soluble endoglin prevents inflammation were studied. We found that in sEng+ animals the increment of proinflammatory cytokines, TNFα, IL1β and IL6, induced by the inflammatory stimulus was reduced. Soluble endoglin also prevents the augmented adhesion molecules, ICAM, VCAM and E-selectin induced by the inflammatory stimulus. In addition, vascular permeability increased by inflammatory agents was also reduced by soluble endoglin. These results suggest that soluble endoglin modulates inflammatory-related diseases and open new perspectives leading to the development of novel and targeted approaches for the prevention and treatment of cardiovascular diseases.</p></div

Proyecto para el desarrollo de un plan de tutorías en la Facultad de Farmacia de la Universidad de Salamanca

Se diseñan programas de incorporación a la universidad, y de tutorías y orientación para los alumnos de nuevo ingreso en la Facultad de Farmacia de Salamanca. Se realizan jornadas de acogida para los alumnos de nuevo ingreso en las que se facilitan el primer contacto y conocimiento entre los compañeros, se conoce el centro, sus instalaciones y servicios, y se facilita el inicio del curso, la incorporación al centro, y el conocimiento de los profesores. Después de la realización de las jornadas se realiza una encuesta a los asistentes. Para la realización del plan de tutorías, se realiza un listado con los nombres de los alumnos y se asignan a cada tutor. Los tutores desarrollan reuniones individuales y grupales con los alumnos asignados. Para favorecer el contacto entre el tutor y el alumno se desarrollan actividades académicas y se adquieren más ordenadores para facilitar la comunicación por correo electrónico. Se pretende habilitar un aula para que se centralicen las actividades del plan de tutorías.Castilla y LeónConsejería de Educación. Dirección General de Universidades e Investigación; Monasterio de Nuestra Señora de Prado, Autovía Puente Colgante s. n.; 47071 Valladolid; +34983411881; +34983411939;ES

Inflammatory cytokines in BAL and air-pouch lavage.

<p>Quantitative analysis of proinflammatory cytokines (TNFα, IL1β and IL6) in BAL and air pouch lavage was performed by ELISA and presented as picograms per milliliter of lavage. Data are expressed as mean ± SEM. n = 5 in each group of mice. (A) TNFα concentration in BAL, +p<0,0001 LPS <i>vs</i> control, two-way ANOVA; (B) TNFα concentration in air pouch lavage, +p<0,05 carrageenan <i>vs</i> control, two-way ANOVA; (C) IL1β concentration in BAL, *p<0,05 <i>vs</i> LPS WT, T test; (D) IL1β concentration in air pouch lavage, +p<0,01 carrageenan <i>vs</i> control, two-way ANOVA; (E) IL6 concentration in BAL, #p<0,001 <i>vs</i> control sEng+, T test; *p<0,05 <i>vs</i> LPS, T test; (F) IL6 concentration in air pouch lavage, *p<0,05 <i>vs</i> carrageenan WT, T test.</p