Double-blind comparison of ropivacaine 7.5 mg ml(-1) with bupivacaine 5 mg ml(-1) for sciatic nerve block.
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Two groups of 12 patients had a sciatic nerve block performed with 20 ml of either ropivacaine 7.5 mg ml(-1) or bupivacaine 5 mg ml(-1). There was no statistically significant difference in the mean time to onset of complete anaesthesia of the foot or to first request for post-operative analgesia. The quality of the block was the same in each group. Although there was no statistically significant difference in the mean time to peak plasma concentrations the mean peak concentration of ropivacaine was significantly higher than that of bupivacaine. There were no signs of systemic local anaesthetic toxicity in any patient in either group. (+info)
Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188.
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Vascular endothelial growth factor (VEGF)-mediated angiogenesis is an important part of bone formation. To clarify the role of VEGF isoforms in endochondral bone formation, we examined long bone development in mice expressing exclusively the VEGF120 isoform (VEGF120/120 mice). Neonatal VEGF120/120 long bones showed a completely disturbed vascular pattern, concomitant with a 35% decrease in trabecular bone volume, reduced bone growth and a 34% enlargement of the hypertrophic chondrocyte zone of the growth plate. Surprisingly, embryonic hindlimbs at a stage preceding capillary invasion exhibited a delay in bone collar formation and hypertrophic cartilage calcification. Expression levels of marker genes of osteoblast and hypertrophic chondrocyte differentiation were significantly decreased in VEGF120/120 bones. Furthermore, inhibition of all VEGF isoforms in cultures of embryonic cartilaginous metatarsals, through the administration of a soluble receptor chimeric protein (mFlt-1/Fc), retarded the onset and progression of ossification, suggesting that osteoblast and/or hypertrophic chondrocyte development were impaired. The initial invasion by osteoclasts and endothelial cells into VEGF120/120 bones was retarded, associated with decreased expression of matrix metalloproteinase-9. Our findings indicate that expression of VEGF164 and/or VEGF188 is important for normal endochondral bone development, not only to mediate bone vascularization but also to allow normal differentiation of hypertrophic chondrocytes, osteoblasts, endothelial cells and osteoclasts. (+info)
TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression.
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The development of endochondral bones requires the coordination of signals from several cell types within the cartilage rudiment. A signaling cascade involving Indian hedgehog (Ihh) and parathyroid hormone related peptide (PTHrP) has been described in which hypertrophic differentiation is limited by a signal secreted from chondrocytes as they become committed to hypertrophy. In this negative-feedback loop, Ihh inhibits hypertrophic differentiation by regulating the expression of Pthrp, which in turn acts directly on chondrocytes in the growth plate that express the PTH/PTHrP receptor. Previously, we have shown that PTHrP also acts downstream of transforming growth factor beta (TGFbeta) in a common signaling cascade to regulate hypertrophic differentiation in embryonic mouse metatarsal organ cultures. As members of the TGFbeta superfamily have been shown to mediate the effects of Hedgehog in several developmental systems, we proposed a model where TGFbeta acts downstream of Ihh and upstream of PTHrP in a cascade of signals that regulate hypertrophic differentiation in the growth plate. This report tests the hypothesis that TGFbeta signaling is required for the effects of Hedgehog on hypertrophic differentiation and expression of PTHRP: We show that Sonic hedgehog (Shh), a functional substitute for Ihh, stimulates expression of Tgfb2 and Tgfb3 mRNA in the perichondrium of embryonic mouse metatarsal bones grown in organ cultures and that TGFbeta signaling in the perichondrium is required for inhibition of differentiation and regulation of Pthrp expression by Shh. The effects of Shh are specifically dependent on TGFbeta2, as cultures from Tgfb3-null embryos respond to Shh but cultures from Tgfb2-null embryos do not. Taken together, these data suggest that TGFbeta2 acts as a signal relay between Ihh and PTHrP in the regulation of cartilage hypertrophic differentiation. (+info)
An unusual case of a postoperative bone cyst.
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We describe an unusual case of a postoperative bone cyst resulting from a retained fragment of surgical glove. We highlight some of the problems associated with gloves and suggest ways of safeguarding against similar complications. (+info)
Interleukin 17 synergises with tumour necrosis factor alpha to induce cartilage destruction in vitro.
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BACKGROUND: Interleukin 17 (IL17) is produced by activated T cells and has been implicated in the development of bone lesions and cartilage degradation in rheumatoid arthritis (RA). OBJECTIVE: To determine whether IL17, alone or together with tumour necrosis factor alpha (TNFalpha), induces cartilage destruction in vitro. METHODS: Fetal mouse metatarsals stripped of endogenous osteoclast precursors were used to study the effect of IL17 on cartilage degradation independently of osteoclastic resorption. Cartilage destruction was analysed histologically by Alcian blue staining. RESULTS: IL17 alone, up to 100 ng/ml, had no effect on the cartilage of fetal mouse metatarsals. IL17 (>/=0.1 ng/ml), however, induced severe cartilage degradation when given together with TNFalpha (>/=1 ng/ml). The cytokine combination decreased Alcian blue staining, a marker of proteoglycans, throughout the metatarsals and induced loss of the proliferating and early hypertrophic chondrocyte zones. TNFalpha alone also decreased Alcian blue staining, but not as dramatically as the cytokine combination. In addition, it did not induce loss of chondrocyte zones. Treatment with inhibitors of matrix metalloproteinase (MMP) activity and nitric oxide synthesis showed that MMP activity played a part in cartilage degradation, whereas nitric oxide production did not. CONCLUSIONS: IL17, together with TNFalpha, induced cartilage degradation in fetal mouse metatarsals in vitro. IL17 may, therefore, participate in the development of cartilage destruction associated with RA by enhancing the effects of TNFalpha and may provide a potential therapeutic target. (+info)
Grasping primate origins.
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The evolutionary history that led to Eocene-and-later primates of modern aspect (Euprimates) has been uncertain. We describe a skeleton of Paleocene plesiadapiform Carpolestes simpsoni that includes most of the skull and many postcranial bones. Phylogenetic analyses indicate that Carpolestidae are closely related to Euprimates. C. simpsoni had long fingers and an opposable hallux with a nail. It lacked orbital convergence and an ankle specialized for leaping. We infer that the ancestor of Euprimates was primitively an arboreal grasper adapted for terminal branch feeding rather than a specialized leaper or visually directed predator. (+info)
In vitro and in vivo endochondral bone formation models allow identification of anti-angiogenic compounds.
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A major obstacle in the study of angiogenesis and the testing of new agents with anti-angiogenic potential has been the lack of experimental models with predictive in vivo value. We describe here the combined use of in vitro and in vivo angiogenesis models that are based on endochondral bone development. This approach led to the identification of a new inhibitor of matrix metalloprotease (MMP) activity that inhibits neovascularization in vitro and in vivo while osteoclast invasion, which occurs simultaneously during bone development, remained unaffected. In contrast, the broad-spectrum MMP-inhibitor marimastat inhibited both in vitro angiogenesis and osteoclastogenesis dose-dependently but displayed severe toxic side effects in vivo. The combined use of these experimental models may, therefore, facilitate the discovery of mechanisms underlying angiogenesis and lead to identification of new pharmacological compounds with clinical efficacy and appropriate selectivity in the treatment of angiogenesis-dependent disorders like arthritis and cancer. (+info)
Skeletal changes in type-2 diabetic Goto-Kakizaki rats.
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We characterized appendicular and axial bones in rats with type-2 diabetes in five female Goto-Kakizaki (GK) rats, a strain developed from the Wistar rat showing spontaneous type-2 diabetes, and five age- and sex-matched non-diabetic Wistar rats. The humerus, tibia, metatarsals and vertebral bodies were analysed by peripheral quantitative computerized tomography (pQCT). In diabetic rats, the height of the vertebral bodies and length of the humerus were decreased while the length of the metatarsals was increased. A decreased cross-sectional area was found in the vertebral end-plate region and the tibial metaphysis. Notably, the diaphysis in all long bones showed expansion of periosteal and endosteal circumference. In tibia this resulted in increased cortical thickness, whereas in humerus and metatarsal it was unchanged. Areal moment of inertia was increased in all diaphyses suggesting greater bending strength. The most conspicuous finding in diabetic rats pertained to trabecular osteopenia. Thus, trabecular bone mineral density was significantly reduced in all bones examined, by 33-53%. Our pQCT study of axial and appendicular bones suggests that the typical feature of diabetic osteopathy in the GK rat is loss of trabecular bone and expansion of the diaphysis. The loss of metaphyseal trabecular bone if also present in diabetic patients may prove to underlie the susceptibility to periarticular fracture and Charcot arthropathy. The findings suggest that the risk of fracture in diabetes varies according to the specific sub-regions of a bone. The approach described may prove to be useful in the early detection of osteopathy in diabetic patients who may be amenable to preventive treatment. (+info)