Efecto del condroitín sulfato en la sinovitis de pacientes con artrosis de rodilla

Objetivo: Evaluar mediante ecografía el efecto del condroitín sulfato (CS) en la sinovitis de pacientes conartrosis (OA) de rodilla, y colaborar en el conocimiento de los mecanismos bioquímicos involucrados enla inflamación sinovial.Métodos: Estudio controlado, aleatorizado, ciego simple de 70 pacientes con OA de rodilla tratadosdurante 6 meses con CS o paracetamol (PCT). Los pacientes fueron visitados a tiempo basal, a las 6semanas, y a los 3 y 6 meses para valorar el estado de su OA según los siguientes parámetros: sinovi-tis evaluada mediante ecografía (según definición de expertos OMERACT); dolor y función, mediante laescala visual analógica y el índice de Lequesne; y concentración de mediadores inflamatorios en suero ylíquido sinovial, mediante ELISA.Resultados: El tratamiento con CS redujo en un 50% el número de individuos que presentaban sinovitis;sin embargo, se observó un incremento de un 123% en el grupo tratado con PCT. En los pacientes sinsinovitis inicial, se observó el establecimiento de esta en un 85,71 y 25% de los casos tratados con PCT yCS, respectivamente. Ambas terapias mejoraron la función articular, pero únicamente el tratamiento conCS produjo una mejora significativa del dolor al final del tratamiento. Se observó una asociación entre eltratamiento con CS y los cambios en la concentración de RANTES y UCN en el líquido sinovial.Conclusiones: El tratamiento con CS tiene un efecto mantenido beneficioso, previniendo la aparición desinovitis o disminuyendo su presencia, así como reduciendo los síntomas de la artrosis. El PCT tambiénmejora los síntomas clínicos, pero no tiene ningún efecto sobre la inflamación. Las variaciones observadasen la concentración de RANTES y UCN podrían estar relacionadas con el efecto antiinflamatorio asociadoal tratamiento con CS

Discrepancies in Composition and Biological Effects of Different Formulations of Chondroitin Sulfate

Osteoarthritis is a common, progressive joint disease, and treatments generally aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease progression. One such agent is chondroitin sulfate-a complex, heterogeneous polysaccharide. It is extracted from various animal cartilages, thus has a wide range of molecular weights and different amounts and patterns of sulfation. Chondroitin sulfate has an excellent safety profile, and although various meta-analyses have concluded that it has a beneficial effect on symptoms and structure, others have concluded little or no benefit. This may be due, at least partly, to variations in the quality of the chondroitin sulfate used for a particular study. Chondroitin sulfate is available as pharmaceutical- and nutraceutical-grade products, and the latter have great variations in preparation, composition, purity and effects. Moreover, some products contain a negligible amount of chondroitin sulfate and among samples with reasonable amounts, in vitro testing showed widely varying effects. Of importance, although some showed anti-inflammatory effects, others demonstrated weak effects, and some instances were even pro-inflammatory. This could be related to contaminants, which depend on the origin, production and purification process. It is therefore vitally important that only pharmaceutical-grade chondroitin sulfate be used for treating osteoarthritis patient

Ser129D mutant alpha-synuclein induces earlier motor dysfunction while S129A results in distinctive pathology in a rat model of Parkinson's disease

Alpha-synuclein phosphorylated at serine 129 (S129) is highly elevated in Parkinson's disease patients where it mainly accumulates in the Lewy bodies. Several groups have studied the role of phosphorylation at the S129 in alpha-synuclein in a rat model for Parkinson's disease using recombinant adeno-associated viral (rAAV) vectors. The results obtained are inconsistent and accordingly the role of S129 phosphorylation in alpha-synuclein toxicity remains unclear. This prompted us to re-examine the neuropathological and behavioral effects of the S129 modified alpha-synuclein species in vivo. For this purpose, we used two mutated forms of human alpha-synuclein in which the S129 was replaced either with an alanine (S129A), to block phosphorylation, or with an aspartate (S129D), to mimic phosphorylation, and compared them with the wild type alpha-synuclein. This approach was similar in design to previous studies, however our investigation of dopaminergic degeneration also included performing a detailed study of the alpha-synuclein induced pathology in the striatum and the analysis of motor deficits. Our results showed that overexpressing S129D or wild type alpha-synuclein resulted in an accelerated dopaminergic fiber loss as compared with S129A alpha-synuclein. Furthermore, the motor deficit seen in the group treated with the mutant S129D alpha-synuclein appeared earlier than the other two forms of alpha-synuclein. Conversely, S129A alpha-synuclein showed significantly larger pathological alpha-synuclein-positive inclusions, and slower dopaminergic fiber loss, when compared to the other two forms of alpha-synuclein, suggesting a neuroprotective effect of the mutation. When examined at long-term, all three alpha-synuclein forms resulted in pathological accumulations of alpha-synuclein in striatal fibers and dopaminergic cell death in the substantia nigra. Our data show that changes in the S129 residue of alpha-synuclein influence the rate of pathology and neurodegeneration, with an overall deleterious effect of exchanging S129 to a residue mimicking its phosphorylated state. (c) 2013 Elsevier Inc. All rights reserved