This study suggests an important involvement of adipokines in OA patients considering their high serum levels compared to controls. Associations of systemic adipokines with local synovial tissue inflammation were found, although not represented by similar relations with cartilage damage, suggesting that adipokines are of relevance in the inflammatory component of OA.
Using this novel approach we were able to demonstrate an in vivo generated chondrobeneficial effect of celecoxib in patients with end stage knee OA.
There is an inverse relation between cartilage AGEs and actual cartilage damage in end-stage OA. This is likely due to ongoing (ineffective) increased turnover of cartilage matrix proteins even in end stage disease.
After the Rotterdam Marathon on 21 April 1991 (ambient temperature 5.80C, relative humidity 74%, wind velocity 5 m s-1) data from 66 athletes were analysed for information concerning total recovery and recovery from pain, stiffness, loss of appetite, sleep disturbance and fatigue.The pulse rate, body weight and temperature were measured. The athletes were divided at random into two groups. Thirty-four athletes received an intravenous infusion of 2.51 of a 2.5% glucose/0.45% NaCl solution. Thirty-two athletes received a placebo infusion of 100ml 0.9% NaCl. Recovery took 9.2 days in the placebo group and 10.2 days in the infusion group. All athletes had pain and/or stiffness after the marathon. The immediate replacement of 2.51 of fluid had no significant influence on the rate of total recovery, the number of days with pain or stiffness, the appetite, sleep or fatigue. On the first day after the marathon the pulse rate was increased. The rectal temperature was not affected. The athletes were also divided into fast and slow runners without regard to fluid replacement. Fast runners (those running the race in less than 2 h 55 min) needed more time to recover than slower runners and pain and/or stiffness lasted longer in the fast group. Athletes who equalled or improved their best previous result also needed more A search of the literature showed that there are almost no data available dealing with recovery after a marathon race. Therefore a study was designed to gather information about the recovery of marathon runners and the effect of intravenous fluid infusion immediately following the race. Subjects and methodsOur study population was chosen from the list of competitors. Experienced male marathon runners were selected. Only those who had completed a previous marathon in less than 3 h and were members of a Dutch track and field club were entered in the study. Of the 382 athletes who fulfilled the above requirements 263 were selected because they lived in, or in the vicinity of, Rotterdam, or in one of the other big cities in the Netherlands. These 263 athletes were asked by informative letter to participate in our investigation. We received a positive response from 98 athletes. The athletes were divided at random into two groups. The participants in each group were to receive an i.v. infusion (100ml 0.9% NaCl in group 1 and 2.512.5% glucose/0.45% NaCl in group 2) administered by anaesthetists and their auxiliaries. The infusions were administered to groups 1 and 2 in separate rooms. All athletes had a cooling down period of approximately 30 min. The 100-ml infusion took on average 15 min, whereas the 2.5-1 infusion was completed after about 50min. Questions concerning recovery, pain, stiffness, loss of appetite, sleep disturbance and fatigue, were answered by the athletes on the 36 days following the marathon by filling in a questionnaire. The questions were answered by using a visual analogue scale of 0-10. On days 1, 3, 7, 14 and 21 the athletes were asked to determine their weight, pulse rate and rectal tempe...
BackgroundSeveral studies suggest that celecoxib has beneficial effects on degenerated cartilage (1, 2). Together with effects on synovial tissue and bone, celecoxib was postulated to have disease modifying osteoarthritic drug (DMOAD) activity.ObjectivesThis study evaluated the DMOAD activity of celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor compared to no treatment and naproxen, treating end-stage knee osteoarthritis (OA), after in vivo exposure using detailed ex vivo tissue analyses.Methods172 patients with end-stage knee OA were randomized to 4 groups and treated for 4 weeks prior to knee replacement surgery: celecoxib 2dd200g, naproxen 3dd250mg, celecoxib 2dd200mg stopped 3 days prior to surgery, or no treatment. To determine if treatment had reached the joint, intra-articular COX-2 expression was determined by Western Blot analysis in the celecoxib until surgery and no treatment group, considering these as most extremes. Proteoglycan release, as primary outcome and content were determined by staining and precipitation of glycosaminoglycans (GAGs) with Alcian Blue. Release of newly formed proteogylcans, as a measure of proteoglycan retention, was determined by loss of 35SO42-labeled GAGs in culture medium by precipitation of GAGs and subsequent liquid scintillation analysis. Synovial tissue inflammation markers interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by Enzyme Linked Immuno Sorbet Assay (ELISA) and nitric oxide (NO) production by standard Griess reaction. Western Ontario and McMaster University (WOMAC) questionnaire was used to evaluate clinical parameters.ResultsIntra-articular COX-2 expression was significantly decreased in both cartilage and synovial tissue (figure 1) indicating proper in vivo exposure of the treatment.Despite this reduction, no significant effect on proteoglycan release, retention or content was found for none of the treatment groups (table 1). Synovial tissue showed only a small decrease in nitric oxide levels in celecoxib treated patients. No clear clinical effects could be observed as indicated by the WOMAC scores.ConclusionsNo effect of a 4-week in vivo celecoxib treatment on joint tissue in knee OA patients could be detected, although decreased expression of COX-2 confirmed its intra-articular availability. Effects on synovial inflammatory mediators and clinical outcome were very limited. No adverse effects were found either. As such the previous reported disease modifying effects of celecoxib in in vitro and pilot clinical studies could not unambiguously be confirmed in this randomized trial.References de Boer TN, Huisman AM, Polak AA, Niehoff AG, van Rinsum AC, Saris D, et al. The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2009;17(4):482–8.Mastbergen SC, Jansen NW, Bijlsma JW, Lafeber FP. Differential direct effects of cyclo-oxygenase-1/2 inhibition on proteoglycan turnov...
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