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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. Source

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. Source

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. Source

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. Source

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. Source

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