Different Type of Microscope

Multiple drilling is reported to be an effective treatment for osteonecrosis of the head of femur, but its effect on intra-osseous pressure has not been described. We undertook multiple drilling and recorded the intra-osseous pressure in 75 osteonecrotic hips in 60 patients with a mean age of 42 years (19 to 67). At a mean follow-up of 37.1 months (24 to 60), 42 hips (56%) had a clinically successful outcome. The procedure was effective in reducing the mean intra-osseous pressure from 57 mmHg (SD 22) to 16 mmHg (SD 9). Hips with a successful outcome had a mean pressure of 26 mmHg (SD 19). It was less effective in preventing progression of osteonecrosis in hips with considerable involvement and in those with a high intra-osseous pressure in the intertrochanteric region (mean 45 mmHg (SD 25)). This study is not able to answer whether a return of the intra-osseous pressure to normal levels is required for satisfactory healing.

purpose. Tissue inhibitor of metalloprotease (TIMP)-3 is an inhibitor of matrix metalloprotease (MMP) and regulates angiogenesis. In the eye, TIMP3 is tightly associated with Bruch’s membrane. In this study, the authors analyzed mice lacking TIMP3 for retinal abnormalities.

methods. Mice with targeted disruption of the Timp3 gene were generated (Timp3^–/–) and bred into C57/Bl6 and CD1 backgrounds. Eyes were analyzed by light and electron microscopy. Vasculature was examined by scanning laser ophthalmoscopy, corrosion casts, and whole mount preparations. MMP activity was assessed by in situ zymography, angiogenic potential was evaluated by tube formation, and aortic ring assays and signaling pathways were studied by immunoblotting.

results. TIMP3-deficient mice develop abnormal vessels with dilated capillaries throughout the choroid. Enhanced MMP activity in the choroid region of Timp3^–/– eyes was detected when compared with controls. Timp3^–/–-derived tissue showed an increased angiogenic activity over wild-type, an effect that could specifically be inhibited by recombinant TIMP3. Moreover, the antiangiogenic property of TIMP3 was demonstrated to reside within the C-terminal domain. When VEGFR2 inhibitor was added to Timp3^–/– aortic explants, endothelial sprout formation was markedly reduced, which provided evidence for an unbalanced VEGF-mediated angiogenesis in Timp3^–/– animals. Finally, angiogenic signaling pathways are activated in Timp3^–/–-derived cells.

conclusions. These findings suggest that the distinct choroidal phenotype in mice lacking TIMP3 may be the result of a local disruption of extracellular matrix and angiogenic homeostasis, and they support an important role of TIMP3 in the regulation of choroidal vascularization.