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Arnalich F.,Hospital Universitario La Paz | Maldifassi M.C.,Autonomous University of Madrid | Atienza G.,Autonomous University of Madrid | Ciria E.,Hospital Universitario La Paz | And 6 more authors.
Cytokine | Year: 2012

Introduction: Plasma vascular endothelial growth factor (VEGF) was shown to increase during acute hypoglycemia and could mediate rapid adaptation of the brain. In this study we examined the neuroendocrine response in patients with type 2 diabetes mellitus (T2DM) in hypoglycemic coma or with acute neuroglycopenic symptoms. Methods: We prospectively studied 135 consecutive T2DM patients admitted for severe hypoglycemia during a 2-year period. We collected clinical variables and measured plasma concentrations of VEGF, epinephrine, norepinephrine, cortisol and growth hormone at admission and 30. min afterwards. Results: Thirty two patients developed hypoglycemic coma and 103 did not lose consciousness. Median plasma VEGF level of coma patients was 3.1-fold lower at baseline than that of non-coma patients, and even 5.3-fold lower 30. min afterwards. Plasma epinephrine concentration was significantly lower just at baseline in coma patients. On the contrary, there were no differences in concentrations of the other hormones. Multivariate logistic regression analysis showed that VEGF concentration (OR 0.68; CI 0.51-0.95) was a protective factor against the development of coma. Conclusions: VEGF and epinephrine responses to acute hypoglycemia are reduced in T2DM patients who develop hypoglycemic coma. An increased plasma VEGF concentration appeared to be a protective factor against the development of hypoglycemic coma. © 2011 Elsevier Ltd. Source

Navarro-Munoz M.,Autonomous University of Barcelona | Ibernon M.,Autonomous University of Barcelona | Bonet J.,Autonomous University of Barcelona | Perez V.,Autonomous University of Barcelona | And 10 more authors.
Kidney and Blood Pressure Research | Year: 2012

Background/Aims: Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity. Methods: Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select differential peptides. Tentative identification of the differential peptides was carried out by HPLC-MS/MS. Results: The HPLC-MS/MS results suggest that uromodulin (UMOD; m/z: 1682, 1898 and 1913) and α1- antitrypsin (A1AT; m/z: 1945, 2392 and 2505) are differentially expressed urinary peptides that distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT peptide abundance was observed in 80-92% of patients with GKD. Proliferative forms of GKD were distinguished from nonproliferative forms, based on a combination of UMOD and A1AT peptides. Nonproliferative forms correlated with higher A1AT peptide levels - focal segmental glomerulosclerosis was linked more closely to high levels of the m/z 1945 peptide than minimal change disease. Conclusion: We describe a workflow - urinary peptide profiling coupled with histological findings - that can be used to distinguish GKD accurately and noninvasively, particularly its nonproliferative forms. Copyright © 2012 S. Karger AG. Source

Gutierrez-Fernandez M.,Hospital Universitario La Paz | Rodriguez-Frutos B.,Hospital Universitario La Paz | Ramos-Cejudo J.,Hospital Universitario La Paz | Teresa Vallejo-Cremades M.,Hospital Universitario La Paz | And 3 more authors.
Stem Cell Research and Therapy | Year: 2013

Introduction. Stem cell therapy can promote good recovery from stroke. Several studies have demonstrated that mesenchymal stem cells (MSC) are safe and effective. However, more information regarding appropriate cell type is needed from animal model. This study was targeted at analyzing the effects in ischemic stroke of acute intravenous (i.v.) administration of allogenic bone marrow- (BM-MSC) and adipose-derived-stem cells (AD-MSC) on functional evaluation results and brain repair markers. Methods. Allogenic MSC (2 × 10§ssup§6 §esup§cells) were administered intravenously 30 minutes after permanent middle cerebral artery occlusion (pMCAO) to rats. Infarct volume and cell migration and implantation were analyzed by magnetic resonance imaging (MRI) and immunohistochemistry. Function was evaluated by the Rogers and rotarod tests, and cell proliferation and cell-death were also determined. Brain repair markers were analyzed by confocal microscopy and confirmed by western blot. Results: Compared to infarct group, function had significantly improved at 24 h and continued at 14 d after i.v. administration of either BM-MSC or AD-MSC. No reduction in infarct volume or any migration/implantation of cells into the damaged brain were observed. Nevertheless, cell death was reduced and cellular proliferation significantly increased in both treatment groups with respect to the infarct group. At 14 d after MSC administration vascular endothelial growth factor (VEGF), synaptophysin (SYP), oligodendrocyte (Olig-2) and neurofilament (NF) levels were significantly increased while those of glial fiibrillary acid protein (GFAP) were decreased. Conclusions: i.v. administration of allogenic MSC - whether BM-MSC or AD-MSC, in pMCAO infarct was associated with good functional recovery, and reductions in cell death as well as increases in cellular proliferation, neurogenesis, oligodendrogenesis, synaptogenesis and angiogenesis markers at 14 days post-infarct. © 2013 Gutiérrez-Fernández et al.; licensee BioMed Central Ltd. Source

Aguado-Fraile E.,Instituto Ramon Y Cajal Of Investigacion Sanitaria Irycis | Ramos E.,Instituto Ramon Y Cajal Of Investigacion Sanitaria Irycis | Saenz-Morales D.,Instituto Ramon Y Cajal Of Investigacion Sanitaria Irycis | Conde E.,Instituto Ramon Y Cajal Of Investigacion Sanitaria Irycis | And 7 more authors.
PLoS ONE | Year: 2012

Ischemia/reperfusion (I/R) is at the basis of renal transplantation and acute kidney injury. Molecular mechanisms underlying proximal tubule response to I/R will allow the identification of new therapeutic targets for both clinical settings. microRNAs have emerged as crucial and tight regulators of the cellular response to insults including hypoxia. Here, we have identified several miRNAs involved in the response of the proximal tubule cell to I/R. Microarrays and RT-PCR analysis of proximal tubule cells submitted to I/R mimicking conditions in vitro demonstrated that miR-127 is induced during ischemia and also during reperfusion. miR-127 is also modulated in a rat model of renal I/R. Interference approaches demonstrated that ischemic induction of miR-127 is mediated by Hypoxia Inducible Factor-1alpha (HIF-1α) stabilization. Moreover, miR-127 is involved in cell-matrix and cell-cell adhesion maintenance, since overexpression of miR-127 maintains focal adhesion complex assembly and the integrity of tight junctions. miR-127 also regulates intracellular trafficking since miR-127 interference promotes dextran-FITC uptake. In fact, we have identified the Kinesin Family Member 3B (KIF3B), involved in cell trafficking, as a target of miR-127 in rat proximal tubule cells. In summary, we have described a novel role of miR-127 in cell adhesion and its regulation by HIF-1α. We also identified for the first time KIF3B as a miR-127 target. Both, miR-127 and KIF3B appear as key mediators of proximal epithelial tubule cell response to I/R with potential al application in renal ischemic damage management. © 2012 Aguado-Fraile et al. Source

Lado Tourino I.,European University at Madrid | Naranjo A.C.,European University at Madrid | Negri V.,Institute of Biomedical Research alberto Sols | Cerdan S.,Institute of Biomedical Research alberto Sols | Ballesteros P.,Spanish University for Distance Education (UNED)
Journal of Molecular Graphics and Modelling | Year: 2015

Computational modeling of the translational diffusion of water molecules in anisotropic environments entails vital relevance to understand correctly the information contained in the magnetic resonance images weighted in diffusion (DWI) and of the diffusion tensor images (DTI). In the present work we investigated the validity, strengths and weaknesses of a coarse-grained (CG) model based on the MARTINI force field to simulate water diffusion in a medium containing carbon nanotubes (CNTs) as models of anisotropic water diffusion behavior. We show that water diffusion outside the nanotubes follows Fick's law, while water diffusion inside the nanotubes is not described by a Fick's behavior. We report on the influence on water diffusion of various parameters such as length and concentration of CNTs, comparing the CG results with those obtained from the more accurate classic force field calculation, like the all-atom approach. Calculated water diffusion coefficients decreased in the presence of nanotubes in a concentration dependent manner. We also observed smaller water diffusion coefficients for longer CNTs. Using the CG methodology we were able to demonstrate anisotropic diffusion of water inside the nanotube scaffold, but we could not prove anisotropy in the surrounding medium, suggesting that grouping several water molecules in a single diffusing unit may affect the diffusional anisotropy calculated. The methodologies investigated in this work represent a first step towards the study of more complex models, including anisotropic cohorts of CNTs or even neuronal axons, with reasonable savings in computation time. © 2015 Elsevier Inc. All rights reserved. Source

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