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IntroductionCD4+CD25+/highCD127low/- regulatory T cells (Tregs) play a crucial role in maintaining peripheral tolerance. Data about the frequency of Tregs in rheumatoid arthritis (RA) are contradictory and based on the analysis of peripheral blood (PB) and synovial fluid (SF). Because Tregs exert their anti-inflammatory activity in a contact-dependent manner, the analysis of synovial membrane (SM) is crucial. Published reports regarding this matter are lacking, so we investigated the distribution and phenotype of Tregs in concurrent samples of SM, SF and PB of RA patients in comparison to those of osteoarthritis (OA) patients.MethodsTreg frequency in a total of 40 patients (18 RA and 22 OA) matched for age and sex was assessed by flow cytometry. Functional status was assessed by analysis of cell surface markers representative of activation, memory and regulation.ResultsCD4+ T cells infiltrate the SM to higher frequencies in RA joints than in OA joints (P = 0.0336). In both groups, Tregs accumulate more within the SF and SM than concurrently in PB (P < 0.0001). Relative Treg frequencies were comparable in all compartments of RA and OA, but Treg concentration was significantly higher in the SM of RA patients (P = 0.025). Both PB and SM Tregs displayed a memory phenotype (CD45RO+RA-), but significantly differed in activation status (CD69 and CD62L) and markers associated with Treg function (CD152, CD154, CD274, CD279 and GITR) with only minor differences between RA and OA.ConclusionsTreg enrichment into the joint compartment is not specific to inflammatory arthritis, as we found that it was similarly enriched in OA. RA pathophysiology might not be due to a Treg deficiency, because Treg concentration in SM was significantly higher in RA. Synovial Tregs represent a distinct phenotype and are activated effector memory cells (CD62L-CD69+), whereas peripheral Tregs are resting central memory cells (CD62L+CD69-).

The simulator study allowed an exact characterization of the running-in period and showed a delayed onset of running-in wear. In contrast, the clinical data showed a slow increase in measured ion concentrations. These different wear patterns are probably due to the effects of distribution, accumulation, and excretion of particles and ions in vivo.

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Modular neck implants are an attractive treatment tool in total hip replacement. Concerns remain about the mechanical stability and metal ion release caused by the modular connection. Five different implant designs were investigated in an experimental set-up. In vivo conditions were simulated and the long-term titanium release was measured. Finally, the modular connections were inspected for corrosion processes and signs of fretting. No mechanical failure or excessive corrosion could be identified for the implants tested. The titanium releases measured were extremely low compared to in vivo and in vitro studies and were not in a critical range.Résumé Dans les prothèses totales de hanche l'utilisation d'implants avec col modulaire est d'une utilisation fré-quente et pratique. Néanmoins, cette utilisation laisse persister des doutes sur la stabilité mécanique et sur le relargage des ions métalliques. 5 différents implants ont été étudiés en reproduisant les conditions in vivo, en mesurant le relargage de titane et en évaluant la corrosion et les lésions du col. Ce travail n'a pas permis de mettre en évidence d'échec secondaire à une corrosion excessive, et les taux de titane sont restés extrêmement bas dans les limites de l'acceptable.

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Purpose Biological reactions against wear particles are a common cause for revision in total knee arthroplasty. To date, wear has mainly been attributed to polyethylene. However, the implants have large metallic surfaces that also could potentially lead to metal wear products (metal ions and debris). The aim of this study was to determine the local release of cobalt, chromium, molybdenum and titanium in total knee arthroplasty during a standard knee wear test. Methods Four moderately conforming fixed-bearing implants were subjected to physiological loadings and motions for 5×10 6 walking cycles in a knee wear simulator. Polyethylene wear was determined gravimetrically and the release of metallic wear products was measured using high resolutioninductively coupled plasma-mass spectrometry. Results A polyethylene wear rate of 7.28±0.27 mg/10 6 cycles was determined and the cumulative mass of released metals measured 1.63±0.28 mg for cobalt, 0.47±0.06 mg for chromium, 0.42±0.06 mg for molybdenum and 1.28±0.14 mg for titanium. Conclusion For other metallic implants such as metal-on-metal total hip arthroplasty, the metal wear products can interact with the immune system, potentially leading to immunotoxic effects. In this study about 12 % by weight of the wear products were metallic, and these particles and ions may become clinically relevant for patients sensitive to these materials in particular. Non-metallic materials (e.g. ceramics or suitable coatings) may be considered for an alternative treatment for those patients.

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