Changes in the metabolism of nuclear inositides phosphorylated in the D3 position of the inositol ring, which may act as second messengers, mainly have been linked to cell differentiation. To clarify a possible role of this peculiar class of inositides also during cell proliferation and/or apoptosis, we have examined the issue of whether or not in the osteoblast-like clonal cell line MC3T3-E1 it may be observed an insulin-like growth factor-I (IGF-I)-and platelet-derived growth factor (PDGF)-dependent nuclear translocation of an active phosphatidylinositol 3-kinase (PI 3-K). We found that both the growth factors increased rapidly and transiently both the amount and the activity of immunoprecipitable nuclear PI 3-K. Intranuclear PI 3-K exhibited a massive tyrosine phosphorylation on the p85 regulatory subunit. Moreover, by means of coimmunoprecipitation experiments, we showed the presence, in isolated nuclei, of the p110 catalytic subunit of PI 3-K. Enzyme translocation was blocked by the specific PI 3-K inhibitor LY294002. In contrast, intranuclear translocation of PI 3-K did not occur in response to the proapoptotic cytokine tumor necrosis factor ␣ (TNF-␣). IGF-I was able to counteract the apoptotic stimulus of TNF-␣ and this was accompanied by the intranuclear translocation of PI 3-K. LY294002 inhibited both intranuclear translocation of PI 3-K and the rescuing effect of IGF-I. These findings strongly suggest that an important step in the signaling pathways that mediate both cell proliferation and survival is represented by the intranuclear translocation of PI 3-K. (J Bone Miner Res 2000;15:1716 -1730)
In biopsy specimens from autologous chondrocyte transplantation tissue at two years, there is evidence of the formation of new tissue, which displays varying degrees of organization with some fibrous and fibrocartilaginous features. Long-term follow-up investigations are needed to verify whether, once all of the remodeling processes are completed, the newly formed tissue will acquire the more typical features of articular cartilage.
We report a prospective trial comparing the effectveness of a post-operative flexion regime versus a standard extension regime on the early outcome and on the post-operative blood loss of total knee arthroplasty. Fourty-eight knees were divided into two different post-operative rehabilitation regimes: a flexion regime and an extension regime. The two groups were well matched with respect to age, gender, operation side and pre-op diagnosis. All patients were implanted with a NexGen cemented total knee prosthesis and all operations were performed by the same surgeon. Patients were assessed pre-operatively, at the time of discharge, at 6 weeks and at 12 weeks, and were evaluated by means of the Knee Society Score (KSS) and the WOMAC score, the Clarkson criteria for range of motion and muscolar strength measurement, and the Verbal Numeric Scale (VNS) for the pain. Futhermore, postoperative blood loss was assessed by comparing the volume of blood in the drain at the time of their removal and measuring the difference in preoperative and postoperative blood haemoglobin (Hb) in the 2 groups. Patients subjected to the flexion regime had a better KSS and Womac score after 12 weeks and had less post-operative blood loss, requiring fewer blood transfusions. No differences were found between the two groups in terms of pain and muscolar strength. We believe a flexion regime after a total knee arthroplasty is a valid option of rehabilitation treatment and does not result in an increase in wound problems.
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