Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve

The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc.     

Effects of cognitive behavioral therapy on work outcomes in vocational rehabilitation for participants with schizophrenia spectrum disorders

Designed to help persons with schizophrenia to persist and perform better at job placements, the Indianapolis Vocational Intervention Program (IVIP) is a program of cognitive-behavioral group and individual interventions. While its feasibility has been previously demonstrated, it is unknown whether IVIP assists persons to achieve greater levels of participation in vocational rehabilitation and higher levels of job performance. In this study, 100 participants with schizophrenia or schizoaffective disorder were offered a six month job placement and randomized to receive IVIP (n = 50) or support services (n = 50) matched for treatment intensity. Number of hours worked was recorded weekly and job performance was assessed biweekly using the Work Behavior Inventory with raters blind to condition. t-tests revealed that participants in the IVIP group worked a significantly greater number of weeks than those in the support condition. Also, repeated measures ANOVA revealed the IVIP group worked more hours across that 26 week period as well. And with regards to work performance, repeated measures of the 56 participants who worked for at least two-thirds of the intervention revealed that participants in the IVIP group had generally better work performance than those in the support condition. Results suggest a connection between cognitive-behavioral interventions and higher levels of work performance in people with schizophrenia.     

骨细胞的功能：生物学研究和机理探讨

骨细胞（osteocyte）是在矿化骨基质内名副其实的骨的细胞（bonecell）。通过细胞突触，骨细胞彼此相连，很可能也与骨髓中某些细胞相接，从而形成三维细胞网络。从骨的超微结构看，骨细胞处于很理想的位置，可以担当骨生理的重要调节因子。然而，由于骨细胞处于矿化骨基质深层，对其功能了解甚少。但随着新技术方法的应用，就有可能对这种成骨细胞系中的终末分化细胞进行深入研究，人们也由此对骨细胞的兴趣大增。骨细胞被认为是骨的机械应力感受器，它有可能参与骨重建。骨细胞能分泌具有调节成骨细胞功能的硬骨素（sclerostin）。一种能降低肾脏磷回吸收的激素——调磷因子FGF23也主要源白骨细胞。随着我们对骨细胞了解的深入，清楚显示，骨细胞不仅能影响局部骨转换活性，而且对全身矿物质的体内平衡也有多种功能。因此，对骨细胞的研究，可以为代谢性骨病的治疗探索新的途径。     

Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgery

Background: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients.
Methods: Thirty (≥75 years, gender M9/F21) and 20 (≤60 years, gender M20/F0) patients scheduled to undergo cardiac surgery. A standard anesthesia with fentanyl as an opioid was used. Fentanyl plasma concentrations were measured at the end of surgery and 2 h later. After tracheal extubation, when the pain intensity was at least moderate, blood samples for fentanyl and oxycodone plasma concentration measurements were taken. Thereafter, oxycodone hydrochloride 0.05 mg/kg i.v. was administered. After 15 and 45 min, pain intensity, sedation and oxycodone plasma concentration were determined. This test protocol was repeated twice.
Results: The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients (5.7±2.2 vs. 3.8±1.2 ng/ml, P =0.001). The plasma concentrations of oxycodone were comparable between the groups. The interval between the second and the third oxycodone dose was longer in the elderly patients ( P =0.036). Pain intensity on the verbal rating scale was lower at the 45-min assessment point after all three oxycodone test doses ( P =0.008) and sedation scores were significantly higher after the third dose in the elderly patients ( P =0.035).
Conclusions: In elderly patients, the plasma concentration of fentanyl was higher but plasma levels of oxycodone were at a similar level compared with middle-aged patients. However, the elderly patients had less pain and were more sedated after doses of oxycodone.