Regulation of osteoblast differentiation by Pasteurella multocida toxin (PMT): a role for Rho GTPase in bone formation.

The role of the Rho-Rho kinase signaling pathway on osteoblast differentiation was investigated using primary mouse calvarial cells. The bacterial toxin PMT inhibited, whereas Rho-ROK inhibitors stimulated, osteoblast differentiation and bone nodule formation. These effects correlated with altered BMP-2 and -4 expression. These data show the importance of Rho-ROK signaling in osteoblast differentiation and bone formation. INTRODUCTION: The signal transduction pathways controlling osteoblast differentiation are not well understood. In this study, we used Pasteurella multocida toxin (PMT), a unique bacterial toxin that activates the small GTPase Rho, and specific Rho inhibitors to investigate the role of Rho in osteoblast differentiation and bone formation in vitro. MATERIALS AND METHODS: Primary mouse calvarial osteoblast cultures were used to investigate the effects of recombinant PMT and Rho-Rho kinase (ROK) inhibitors on osteoblast differentiation and bone nodule formation. Osteoblast gene expression was analyzed using Northern blot and RT-PCR, and actin rearrangements were visualized after phalloidin staining and confocal microscopy. RESULTS: PMT stimulated the proliferation of primary mouse calvarial cells and markedly inhibited the differentiation of osteoblast precursors to bone nodules with a concomitant inhibition of osteoblastic marker gene expression. There was no apparent causal relationship between the stimulation of proliferation and inhibition of differentiation. PMT caused cytoskeletal rearrangements because of activation of Rho, and the inhibition of bone nodules was completely reversed by the Rho inhibitor C3 transferase and partly reversed by inhibitors of the Rho effector, ROK. Interestingly, Rho and ROK inhibitors alone potently stimulated osteoblast differentiation, gene expression, and bone nodule formation. Finally, PMT inhibited, whereas ROK inhibitors stimulated, bone morphogenetic protein (BMP)-2 and -4 mRNA expression, providing a possible mechanism for their effects on bone nodule formation. CONCLUSIONS: These results show that PMT inhibits osteoblast differentiation through a mechanism involving the Rho-ROK pathway and that this pathway is an important negative regulator of osteoblast differentiation. Conversely, ROK inhibitors stimulate osteoblast differentiation and may be potentially useful as anabolic agents for bone.     

The emerging role of induced hypothermia in the management of acute stroke.

Current treatment of acute stroke remains unsatisfactory. This review presents experimental and clinical data which suggest that mild induced hypothermia could be a potent and practicable neuroprotective treatment of acute ischaemic stroke and intracerebral haemorrhage. Hypothermia, if proven to be safe, effective and widely practicable in patients with acute stroke, could have an enormous positive impact on reducing the burden of stroke worldwide. Critical issues that will need to be considered in a well designed randomised controlled trial of induced hypothermia in acute stroke patients are discussed.     

Gianotti-Crosti-Syndrom nach Impfung

Es wird über 4 Kleinkinder berichtet, bei denen ein Gianotti-Crosti-Syndrom (GCS) mit einer Latenz von 6–8 Tagen nach Impfung auftrat. Nachfolgende Auffrischungsimpfungen wurden problemlos vertragen. W?hrend das Auftreten eines GCS in Assoziation mit einer Virusinfektion gut dokumentiert ist, liegen über das Auftreten eines GCS im Anschluss an eine Impfung nur wenige Mitteilungen vor. Auf einen derartig m?glichen Zusammenhang sollte jedoch bei Vorstellung dieses Krankheitsbildes (GCS) im Rahmen der Anamneseerhebung unbedingt eingegangen werden.     

Percutaneous transhepatic placement of biliary endoprostheses: results in 100 consecutive patients.

One hundred patients with malignant biliary obstruction underwent palliative therapy by means of percutaneous transhepatic placement of 114 biliary endoprostheses. All patients were then followed up for at least 18 months or until death. Retrospective evaluation of the 95 patients who died showed an average survival time of 5.0 months. The five remaining patients have survived an average of 29.8 months. During the 1st week after stent insertion, a second manipulation was performed to improve stent function in nine patients. Overall, 14 (12.3%) of the stents became obstructed and six (5.2%) migrated; 86 patients required no further therapy for biliary obstruction or stent malfunction. The 30-day mortality rate was 12%; none of the deaths were directly attributable to a complication of the stent placement procedure.     

Bone mineral content in patients with carcinoma of the prostate

This study investigated the effect of metastatic prostatic carcinoma on bone density. Thirty patients underwent a lumbar spine scan with a dual photon absorptiometer. Of these patients, 9 had proven skeletal metastatic deposits in the area being investigated. Comparison of results with a non-matched control population with proven benign prostatic histology showed a significantly elevated linear bone mineral content (BMC) in the disease group. Patients scanned after a 3- or 6-month period of hormonal therapy demonstrated a rise in BMC values, although the trend was not statistically significant. Indices of calcium metabolism have also been investigated.     

肘关节脱位与肱骨远端关节内骨折

Objective To describe dislocation of the elbow with articular fracture of the distal humerus,a type of elbow fracture-dislocation about which little has been written.Methods Four patients with a dislocation of the elbow and fracture of the distal humerus were identified.Three had dislocation and complex intraarticular fracture of the capitellum,trochlea,and lateral epicondyle.Results Two patients(one treated with a second operation to address avascular necrosis of the capitellum)achieved a functional arc of elbow motion and one patient was lost after removal of the implants 3 months after fracture with documented healing.The fourth patient had a complex open fracture dislocation involving the entire articular surface.An attempt to salvage the articular surface resulted in deep infection.Extensive heterotopic bone led to arthrodesis of the elbow.Conclusions Dislocations of the elbow with articular fracture of the humerus are uncommon.Most injuries involve the capitellum,lateral trochlea,and lateral epicondyle.Open reduction and internal fixation of the distal humerus fracture can restore stability without repairing the medial collateral ligament.