Radiocirugía estereotáctica para el tratamiento de la epilepsia, el temblor esencial, la enfermedad de Parkinson, la neuralgia del glosofaríngeo y del trigémino: síntesis de su eficacia, efectividad, seguridad y eficiencia

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Opcions disponibles en la cirurgia de la malaltia de Parkinson i la tremolor essencial

Parkinson; Tremolor; CirurgiaParkinson; Temblor; CirugíaParkinson's; Shaking; SurgeryAquest document conté una revisió de revisions i d’informes de síntesi, en què s’han seleccionat els informes d’avaluació de tecnologies sanitàries i les guies de pràctica clínica, s’han descrit de forma narrativa els resultats i, mitjançant la tècnica qualitativa de grup nominal, s’ha elaborat una taula comparativa amb recomanacions sobre les indicacions per a cada tipus de tècnica quirúrgica.Este documento contiene una revisión de revisiones y de informes de síntesis, en que se han seleccionado los informes de evaluación de tecnologías sanitarias y las guías de práctica clínica. Se han descrito de forma narrativa los resultados y, mediante la técnica cualitativa de grupo nominal, se ha elaborado una mesa comparativa con recomendaciones sobre las indicaciones para cada tipo de técnica quirúrgica.This document contains review of reviews and synthesis reports has been prepared, in which health technology assessment reports and clinical practice guidelines were selected. The results have been described narratively, and, through a qualitative nominal group technique, a comparative table has been drawn up with recommendations on indications for each type surgical intervention

Identification of N-Acyl Hydrazones as New Non-Zinc-Binding MMP-13 Inhibitors by Structure-Based Virtual Screening Studies and Chemical Optimization

Matrix metalloproteinase 13 plays a central role in osteoarthritis (OA), as its overexpression induces an excessive breakdown of collagen that results in an imbalance between collagen synthesis and degradation in the joint, leading to progressive articular cartilage degradation. Therefore, MMP-13 has been proposed as a key therapeutic target for OA. Here we have developed a virtual screening workflow aimed at identifying selective non-zinc-binding MMP-13 inhibitors by targeting the deep S1 & PRIME; pocket of MMP-13. Three ligands were found to inhibit MMP-13 in the & mu;M range, and one of these showed selectivity over other MMPs. A structure-based analysis guided the chemical optimization of the hit compound, leading to the obtaining of a new N-acyl hydrazone-based derivative with improved inhibitory activity and selectivity for the target enzyme

Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening

Matrix metalloproteinases (MMPs) are the family of proteases that are mainly responsible for degrading extracellular matrix (ECM) components. In the skin, the overexpression of MMPs as a result of ultraviolet radiation triggers an imbalance in the ECM turnover in a process called photoaging, which ultimately results in skin wrinkling and premature skin ageing. Therefore, the inhibition of different enzymes of the MMP family at a topical level could have positive implications for photoaging. Considering that the MMP catalytic region is mostly conserved across different enzymes of the MMP family, in this study we aimed to design a virtual screening (VS) workflow to identify broad-spectrum MMP inhibitors that can be used to delay the development of photoaging. Our in silico approach was validated in vitro with 20 VS hits from the Specs library that were not only structurally different from one another but also from known MMP inhibitors. In this bioactivity assay, 18 of the 20 compounds inhibit at least one of the assayed MMPs at 100 μM (with 5 of them showing around 50% inhibition in all the tested MMPs at this concentration). Finally, this VS was used to identify natural products that have the potential to act as broad-spectrum MMP inhibitors and be used as a treatment for photoaging