Superoxide anion (O2  •−) is overproduced in joint inflammation, rheumatoid arthritis, and osteoarthritis. Increased O2  •− production leads to tissue damage, articular degeneration, and pain. In these conditions, the physiological defense against O2  •−, superoxide dismutases (SOD) are decreased. The MnII complex MnL4 is a potent SOD mimetic, and in this study it was tested in inflammatory and osteoarticular rat pain models. In vivo protocols were approved by the animal Ethical Committee of the University of Florence. Pain was measured by paw pressure and hind limb weight bearing alterations tests. MnL4 (15 mg kg−1) acutely administered, significantly reduced pain induced by carrageenan, complete Freund's adjuvant (CFA), and sodium monoiodoacetate (MIA). In CFA and MIA protocols, it ameliorated the alteration of postural equilibrium. When administered by osmotic pump in the MIA osteoarthritis, MnL4 reduced pain, articular derangement, plasma TNF alpha levels, and protein carbonylation. The scaffold ring was ineffective. MnL4 (10−7 M) prevented the lipid peroxidation of isolated human chondrocytes when O2  •− was produced by RAW 264.7. MnL4 behaves as a potent pain reliever in acute inflammatory and chronic articular pain, being its efficacy related to antioxidant property. Therefore MnL4 appears as a novel protective compound potentially suitable for the treatment of joint diseases.

Purpose We evaluated the risk of hypersensitivity to metals in a population of consecutive subjects undergoing a total knee arthroplasty (TKA). We also proposed a diagnostic pathway to address any sensitivity to metals. We finally presented the mid-term outcomes of a full non allergenic knee implant. Methods We developed a protocol based on the medical history, patch testing, and on specific laboratory assays, in order to assess a sensitization to metals. Twenty-four patients (25 knees) with referred or suspected allergy to metals were found in more than 1,000 treated patients, with a mean age of 72.9 years. We proceeded to a radiologic study, a clinical evaluation by the visual analogic scale (VAS), and Knee Society rating system (KSS). In all cases a full anallergic cemented implant with an oxidized zirconium femoral component and an all-polyethylene tibial baseplate was chosen. Results Four (16.6%) of the 24 patients were considered to be hypersensitive to metals. The mean follow-up was 79.2 months. No patient reported any reaction related to hypersensitivity or complications after TKA. The VAS improved from a mean preoperative value of 7.2 to 1.8 postoperatively; the KSS and the functional score increased from 38 to 91 points and from 39 to 88 points, respectively. Conclusions We consider careful research of medical history for metals hypersensitivity crucial, and we perform patch testing and lab assays in case of doubtful sensitization. The choice of a modern hypoallergenic implant may prevent any kind of potential reactions.

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BackgroundAll implant compounds undergo an electrochemical process when in contact with biological fluids, as well as mechanical corrosion due to abrasive wear, with production of metal debris that may inhibit repair processes. None of the commonly-used methods can diagnose implant allergies when used singly, therefore a panel of tests should be performed on allergic patients as pre-operative screening, or when a postoperative metal sensitisation is suspected.MethodsWe analysed patients with painful prostheses and subjects prone to allergies using the Patch Test in comparison with the Lymphocyte Transformation Test. Cytokine production was evaluated to identify prognostic markers for early diagnosis of aseptic loosening. Metal debris endocytosis and cytoskeletal rearrangement was visualised by confocal microscopy.ResultsOur results demonstrate that the Lymphocyte Transformation Test can identify patients who have a predisposition to develop allergic reactions and can confirm the diagnosis of hypersensitivity in patients with painful prostheses.The prevalence of a Th2-cytokine pattern may be used to identify predisposition to the development of allergic diseases, while the selective presence of osteoclastogenic cytokines may be used as predictor of a negative outcome in patients with painful prosthesis.The hypothesis of the prognostic value of these cytokines as early markers of aseptic loosening is attractive, but its confirmation would require extensive testing.ConclusionsThe Lymphocyte Transformation Test is the most suitable method for testing systemic allergies. We suggest that the combined use of the Patch Test and the Lymphocyte Transformation Test, associated with cytokine detection in selected patients, could provide a useful tool for preventive evaluation of immune reactivity in patients undergoing primary joint replacement surgery, and for clinical monitoring of the possible onset of a metal sensitization in patients with implanted devices.