Institute Investigacion Sanitaria Hospital

Madrid, Spain

Institute Investigacion Sanitaria Hospital

Madrid, Spain
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Lozano D.,Institute Investigacion Sanitaria IIS | Lozano D.,Hospital Universitario La Paz | Sanchez-Salcedo S.,Institute Investigacion Sanitaria Hospital | Sanchez-Salcedo S.,Research Center Perteneciente Red Of Bioingenieria | And 9 more authors.
Acta Biomaterialia | Year: 2014

Biopolymer-coated nanocrystalline hydroxyapatite (HA) made as macroporous foams which are degradable and flexible are promising candidates as orthopaedic implants. The C-terminal (107-111) epitope of parathyroid hormone-related protein (PTHrP) exhibits osteogenic properties. The main aim of this study was to evaluate whether PTHrP (107-111) loading into gelatin-glutaraldehyde biopolymer-coated HA (HAGlu) scaffolds would produce an optimal biomaterial for tissue engineering applications. HAGlu scaffolds with and without PTHrP (107-111) were implanted into a cavitary defect performed in both distal tibial metaphysis of adult rats. Animals were sacrificed after 4 weeks for histological, microcomputerized tomography and gene expression analysis of the callus. At this time, bone healing occurred only in the presence of PTHrP (107-111)-containing HAGlu implant, related to an increase in bone volume/tissue volume and trabecular thickness, cortical thickness and gene expression of osteocalcin and vascular cell adhesion molecule 1, but a decreased gene expression of Wnt inhibitors, SOST and dickkopf homolog 1. The autonomous osteogenic effect of the PTHrP (107-111)-loaded HAGlu scaffolds was confirmed in mouse and human osteoblastic cell cultures. Our findings demonstrate the advantage of loading PTHrP (107-111) into degradable HAGlu scaffolds for achieving an optimal biomaterial that is promising for low load bearing clinical applications. © 2014 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.


Izquierdo-Barba I.,Institute Investigacion Sanitaria Hospital | Izquierdo-Barba I.,CIBER ISCIII | Garcia-Martin J.M.,Imm Institute Microelectronica Of Madrid Cnm Csic | Alvarez R.,University of Seville | And 7 more authors.
Acta Biomaterialia | Year: 2015

Bacterial colonization and biofilm formation on orthopedic implants is one of the worst scenarios in orthopedic surgery, in terms of both patient prognosis and healthcare costs. Tailoring the surfaces of implants at the nanoscale to actively promote bone bonding while avoiding bacterial colonization represents an interesting challenge to achieving better clinical outcomes. Herein, a Ti6Al4V alloy of medical grade has been coated with Ti nanostructures employing the glancing angle deposition technique by magnetron sputtering. The resulting surfaces have a high density of nanocolumnar structures, which exhibit strongly impaired bacterial adhesion that inhibits biofilm formation, while osteoblasts exhibit good cell response with similar behavior to the initial substrates. These results are discussed on the basis of a "lotus leaf effect" induced by the surface nanostructures and the different sizes and biological characteristics of osteoblasts and Staphylococcus aureus. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Mellado M.,CSIC - National Center for Biotechnology | Martinez-Munoz L.,CSIC - National Center for Biotechnology | Cascio G.,CSIC - National Center for Biotechnology | Lucas P.,CSIC - National Center for Biotechnology | And 2 more authors.
Frontiers in Immunology | Year: 2015

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies. © 2015 Mellado, Martínez-Muñoz, Cascio, Lucas, Pablos and Rodríguez-Frade.


Vila M.,Institute Investigacion Sanitaria Hospital | Vila M.,CIBER ISCIII | Matesanz M.C.,Complutense University of Madrid | Goncalves G.,University of Aveiro | And 6 more authors.
Nanotechnology | Year: 2014

Graphene oxide (GO) has been proposed as an hyperthermia agent for anticancer therapies due to its near-infrared (NIR) optical absorption ability which, with its small two-dimensional size, could have a unique performance when compared to that of any other nanoparticle. Nevertheless, attention should be given to the hyperthermia route and the kind of GO-cell interactions induced in the process. The hyperthermia laser irradiation parameters, such as exposure time and laser power, were investigated to control the temperature rise and consequent damage in the GOs containing cell culture medium. The type of cell damage produced was evaluated as a function of these parameters. The results showed that cell culture temperature (after irradiating cells with internalized GO) increases preferentially with laser power rather than with exposure time. Moreover, when laser power is increased, necrosis is the preferential cell death leading to an increase of cytokine release to the medium. © 2014 IOP Publishing Ltd.


Gomez-Cerezo N.,Institute Investigacion Sanitaria Hospital | Gomez-Cerezo N.,CIBER ISCIII | Izquierdo-Barba I.,Institute Investigacion Sanitaria Hospital | Izquierdo-Barba I.,CIBER ISCIII | And 4 more authors.
Journal of Materials Chemistry B | Year: 2015

Mesoporous bioactive glasses (MBGs) in the SiO2-CaO-P2O5 system have been prepared using different non-ionic structure directing agents (SDA): Brij58, F68, P123 and F127. For the first time, the bioactive response of MBGs can be tailored with the kind of SDA incorporated. This is because, in addition to the textural properties, we can use the SDA to tailor the local atomic environment within the MBG struts. These features lead to differences in the in vitro bioactive behaviour of MBGs. Among the different SDAs used in this work, the triblock copolymer F68 leads to MBGs that exhibit the fastest bioactivity and the fastest differentiation induction from a pre-osteoblast to an osteoblast phenotype. These results are explained in terms of a highly ordered mesoporous structure, more free calcium cations acting as silica network modifiers and small mesopores that avoid the formation of CaP nuclei within pores, which could obstruct the ionic exchange with the surrounding fluids. This journal is © The Royal Society of Chemistry 2015.


MacDowell K.S.,Complutense University of Madrid | MacDowell K.S.,Research Center Biomedica En Red Of Salud Mental Cibersam | MacDowell K.S.,Institute Investigacion Sanitaria Hospital | Garcia-Bueno B.,Complutense University of Madrid | And 14 more authors.
International Journal of Neuropsychopharmacology | Year: 2013

Inflammation, caused by both external and endogenous factors, has been implicated as a main pathophysiological feature of chronic mental illnesses, including schizophrenia. An increase in pro-inflammatory cytokines has been described both in experimental models and in schizophrenia patients. However, not much is known about the effects that antipsychotic drugs have on intra-and intercellular mechanisms controlling inflammation. The aim of the present study was to investigate the possible anti-inflammatory effect of a standard schizophrenia treatment not only at the level of soluble mediators, but also at intra-and intercellular inflammatory pathways. The present study was conducted in a model of mild neuroinflammation using a lipopolysaccharide (LPS) challenge that was not an endotoxaemic dose (0.5 mg/kg i.p.) in young adult rats. Main results: single doses of risperidone (0.3-3.0 mg/kg i.p.) prevented increased inflammatory parameters induced by LPS in brain cortex [expression of inflammatory cytokines, interleukin (IL)-1β and tumour necrosis factor (TNF)-α, activity of the inducible inflammatory enzymes nitric oxide synthase and cyclooxygenase, p38 mitogen-activated protein kinase (MAPK) and inflammatory nuclear transcription factor κB] and restored anti-inflammatory pathways decreased by LPS challenge (deoxyprostaglandins and peroxisome proliferator activated receptor γ). This is the first study demonstrating that risperidone elicits a preventive effect on the anti-inflammatory arm of the homeostatic mechanism controlling inflammation in a model of mild encephalitis in rats. Our findings suggest a possible protective effect of risperidone on brain cells. © 2011 CINP.


Matesanz M.C.,Complutense University of Madrid | Linares J.,Complutense University of Madrid | Linares J.,CIBER ISCIII | Lilue I.,Complutense University of Madrid | And 8 more authors.
Journal of Materials Chemistry B | Year: 2014

In the present study, the effects of nanocrystalline hydroxyapatite (nano-HA) and nanocrystalline Si-substituted hydroxyapatite (nano-SiHA) on osteoclast differentiation and resorptive activity have been evaluated in vitro using osteoclast-like cells. The action of these materials on proinflammatory and reparative macrophage populations was also studied. Nano-SiHA disks delayed the osteoclast differentiation and decreased the resorptive activity of these cells on their surface, as compared to nano-HA samples, without affecting cell viability. Powdered nano-SiHA also induced an increase of the reparative macrophage population. These results along with the beneficial effects on osteoblasts previously observed with powdered nano-SiHA suggest the potential of this biomaterial for modulating the fundamental processes of bone formation and turnover, preventing bone resorption and enhancing bone formation at implantation sites in treatment of osteoporotic bone and in bone repair and regeneration. © 2014 the Partner Organisations.


PubMed | Institute Investigacion Sanitaria Hospital and CSIC - National Center for Biotechnology
Type: | Journal: Frontiers in immunology | Year: 2015

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies.


Martinez-Morentin L.,Autonomous University of Madrid | Martinez L.,Autonomous University of Madrid | Piloto S.,Sanford Burnham Institute for Medical Research | Yang H.,Columbia University | And 9 more authors.
Human Molecular Genetics | Year: 2015

The heart is a muscle with high energy demands. Hence, most patients with mitochondrial disease produced by defects in the oxidative phosphorylation (OXPHOS) system are susceptible to cardiac involvement. The presentation of mitochondrial cardiomyopathy includes hypertrophic, dilated and left ventricular noncompaction, but the molecular mechanisms involved in cardiac impairment are unknown. One of the most frequent OXPHOS defects in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors such as Sco1 and Sco2. To investigate the molecular mechanisms that underlie the cardiomyopathy associated with Sco deficiency, we have heart specifically interfered scox expression, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. Cardiomyocytes with low levels of scox have a significant reduction in COX activity and they undergo a metabolic switch from OXPHOS to glycolysis, mimicking the clinical features found in patients harbouring Sco mutations. The major cardiac defects observed are produced by a significant increase in apoptosis, which is dp53-dependent. Genetic and molecular evidence strongly suggest that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans. © The Author 2015. Published by Oxford University Press. All rights reserved.


Garcia-Sanchez F.,Hospital Universitario Of Mostoles | Martinez-Gras I.,Hospital Universitario La Paz | Martinez-Gras I.,Institute Investigacion Sanitaria Hospital | Martinez-Gras I.,Research Center Biomedica En Red Of Salud Mental | And 6 more authors.
Revista de Neurologia | Year: 2011

Introduction. Prepulse inhibition (PPI) of startle is an operational measure of the pre-attentive filtering process known as sensorimotor gating. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30-500 ms before a strong startle inducing stimulus, and reduces the magnitude of the startle response. This experimental paradigm has been studied in laboratory animal as well as in patients with schizophrenia. Recently, PPI deficits have been observed in other psychiatric disorders that shared some deficit in cognitive and sensorimotor gating. Development. We have reviewed studies examining prepulse inhibition in humans across some neuropsychiatric disorders for asses the clinical and neurobiological implications of this paradigm. Conclusions. PPI deficits have been observed in multiple psychiatric disorders many of which present a common correlate anatomic-functional and a dysfunction in several neurotransmission systems, mainly dopamine system. These dysfunctions are independent of categorical diagnostic and they have proposed as a biological marker of vulnerability for some psychiatric disorders. © 2011 Revista de Neurología.

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