Stabilization of fibrin-chondrocyte constructs with fibrinolytical inhibitors has been shown to be a feasible method for the reconstruction of cartilage in vitro. In this study, the method was tested in vivo. Autologous cultures were used to form stabilized fibrin-chondrocyte constructs that were injected into auricular cartilage defects of rabbits. Stabilization was achieved by high doses of fibrinolytic inhibitors. Samples were prepared for magnetic resonance imaging, histology, and immunohistochemistry after 1, 2, 4, and 6 months. Defects of the contralateral ear, which were treated with stabilized fibrin without cells, were used for controlled comparisons. In all cell-fibrin samples, cartilage-like tissue was present. Immunohistochemistry revealed the presence of collagen II. This finding was similar for all observations. In the control samples, only minor new cartilage could be detected at the cut edges. The reconstruction of cartilage in vivo by injecting fibrin-chondrocyte constructs, stabilized with inhibitors of fibrinolysis, is thus possible.
Significant improvements of 1-month patient-reported outcomes are achieved in patients attending inpatient as well as outpatient exercise-based cardiac rehabilitation when compared with no exercise-based cardiac rehabilitation. In contrast to inpatient exercise-based cardiac rehabilitation, however, outpatient exercise-based cardiac rehabilitation leads to a further improvement of patient-reported outcomes. These results suggest that, if patients have to be admitted for inpatient exercise-based cardiac rehabilitation, this programme should be followed by an outpatient exercise-based cardiac rehabilitation to further improve and stabilize these patient-reported outcome variables.
These results confirm the antioxidative properties of the study drug, indicating that nimesulide, beside its known anti-inflammatory properties, also shows an evident antioxidative activity that adds further supportive evidence to its key role in the treatment of OA patients (thanks to the absence of degenerative effects on cartilage).
CD3+CD4+CD28null and CD3+CD8+CD28null T cells are enriched in patients with immune-mediated diseases compared with healthy controls. This study shows that CD4+CD28null T cells express Toll-like receptors recognizing bacterial lipopolysaccharides in ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. In ankylosing spondylitis, TLR4 (23.1 ± 21.9%) and, to a smaller extent, TLR2 (4.1 ± 5.8%) were expressed on CD4+CD28null T cells, whereas expression was negligible on CD4+CD28+ and CD8+ T cells. CD4+CD28null T cells produced perforin upon stimulation with lipopolysaccharide, and this effect was enhanced by autologous serum or recombinant soluble CD14. Perforin production could be prevented with blocking antibodies directed against CD14 or TLR4. Incubation of peripheral blood mononuclear cells with tumour necrosis factor alpha led to an upregulation of TLR4 and TLR2 on CD4+CD28null T cells in vitro, and treatment of patients with antibodies specifically directed against tumour necrosis factor alpha resulted in decreased expression of TLR4 and TLR2 on CD4+CD28null T cells in vivo. We describe here a new pathway for direct activation of cytotoxic CD4+ T cells by components of infectious pathogens. This finding supports the hypothesis that CD4+CD28null T cells represent an immunological link between the innate immune system and the adaptive immune system.
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