Introduction

recent studies recognised metabolic abnormalities as additional factors in the development of rotator cuff (RC) tendinopathy. It has been hypothesised that the insertional area of this tendon is susceptible to degenerative changes due to intrinsic hypovascularization. The mechanisms underlying this process are not yet clear. In this study we attempted to confirm if larger lesions of the RC are related to impaired vasodilatatory response of the local circulation in conditions of “hemodynamic stress”.

Summary Statement. The incidence of osteonecrosis was significantly lower in the anti-vasospasm agent group (32%) than that in the control group (75%). Vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis. Introduction. A number of studies have suggested that ischemia is the principal pathomechanism of osteonecrosis, however, the detailed mechanism responsible for ischemia remains unclear. It has recently been reported that the Rho/Rho-kinase mediated pathway (Rho-kinase pathway) is considered to be involved in the possible pathogenesis of various cardiovascular disorders as well as cerebral vasospasm. We examined the effects of fasudil (Rho-kinase inhibitor), an anti-vasospasm agent, on the development of steroid-induced osteonecrosis in rabbits. Materials & Methods. One group of rabbits received 15 mg/kg of fasudil intravenously, which were then injected once intramuscularly with 20 mg/kg of methylprednisolone (n = 33, MF group), and one received methylprednisolone alone as a control (n = 28, M group). Eight rabbits from each group were sacrificed 24 hour after the methylprednisolone injection to analyze them by immunohistochemical staining, a Western blotting analysis. Two weeks after the steroid injection, the femora and humeri were examined histopathologically for the incidence of osteonecrosis. Results. The incidence of osteonecrosis was significantly lower in the MF group (32%) than that in the M group (75%) (P < 0.01). Immunohistochemically, endothelin. A. -receptor (ET. A. Rc) expressions levels were decreased in the smooth muscle of the bone marrow in the MF group in comparison to that in the M group. In the M group, the average relative phospho-myosin light chain (p-MLC) expression level in the bone marrow tissue was significantly higher than that observed in the MF group (P < 0.01). In the MF group, the average relative total-eNOS expression level as well as the average relative phospho-eNOS (p-eNOS) expression level was almost 1.5 times higher than that observed in the M group (P < 0.05). The eNOS expressions levels in both serum and bone marrow in the MF group were significantly higher than those in the M group (P < 0.05). Discussion/Conclusion. The potential mechanisms resulting in vasospasm include the increased release of vasoconstrictors or increased sensitivity to these vasoconstrictors. ET-1 has been demonstrated to cause vascular smooth muscle cell constriction via ET. A. Rc stimulation. The expression of ET. A. Rc in rabbits treated with methylprednisolone plus fasudil (MF group) decreased in comparison with that in rabbits treated with the methylprednisolone alone (M group). In this study, both the eNOS and p-eNOS expressions levels in the M group were decreased in comparison to those observed in the MF group. A previous study suggested that high-dose steroid administration causes the overproduction of reactive oxygen species, and thereby perturbs nitric oxide (NO) availability in the vascular endothelium, leading to vascular endothelial dysfunction in patients receiving high-dose steroid therapy. Considering the pathogenesis of the development of osteonecrosis, we speculate that endothelial dysfunction may thus be a preliminary condition leading to the vasospasm. In conclusion, this study indicates that vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis and that the anti-vasospasm agents seem to decrease the incidence of steroid-induced osteonecrosis

The aim of this study was to examine the effects of cement in total knee arthroplasty on markers of inflammation and endothelial dysfunction, as surrogate markers for enhanced risk of vascular disease or precipitation of acute vascular events post-operatively. A total of 36 patients were recruited, with 18 in each of the cemented and uncemented groups. Both groups were matched for age, sex and body mass index. Venous blood samples were taken pre-operatively, day 1 and day 7 post-operatively. Serum levels of interleukin 6 (IL6), tumour necrosis factor (TNF□?, e-selectin, Von willebrand factor (vWF), tissue plasminogen activator (tPA) and soluble CD40 ligand were analysed. Also, real time analysis of the expression of CD40 and CD14/CD42a aggregates on monocytes was carried out using flow cytometry. Patients were excluded from the study if there were signs of either superficial or deep infection. The only variable to demonstrate a significant difference between the two groups was the CD1442a count. There was a significant difference in the first 24 hours (p=0.00) and from day 1 to day 7 (p=0.02). Our study suggests that the use of bone cement causes a significant rise in CD1442a count which has been linked to atherothrombosis and acute coronary syndromes. These changes may explain the increased incidence of venous thrombosis and thromboembolism post-operatively. However more research required in this field to delineate the exact pathways involved