Ueber Lähmung der Convergenz- und Divergenzfähigkeit

Ohne Zusammenfassung     

A novel GalR2-specific peptide agonist

The galanin peptide family and its three receptors have with compelling evidence been implicated in several high-order physiological disorders. The co-localization with other neuromodulators and the distinct up-regulation during and after pathological disturbances has drawn attention to this neuropeptide family. In the current study we present data on receptor binding and functional response for a novel galanin receptor type 2 (GalR2) selective chimeric peptide, M1145 [(RG)₂-N-galanin(2-13)-VL-(P)₃-(AL)₂-A-amide]. The M1145 peptide shows more than 90-fold higher affinity for GalR2 over GalR1 and a 76-fold higher affinity over GalR3. Furthermore, the peptide yields an agonistic effect in vitro, seen as an increase in inositol phosphate (IP) accumulation, both in the absence or the presence of galanin. The peptide design with a N-terminal extension of galanin(2-13), prevails new insights in the assembly of novel subtype specific ligands for the galanin receptor family and opens new possibilities to apply the galanin system as a putative drug target.     

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.     

Development and evaluation of a case group concept for inpatients with mental disorders in Germany: Using self-report and expert-rated instruments

The aim of this study was to evaluate a case-mix system to classify inpatients with mental disorders in Germany by means of self-report and expert-rated instruments. The use of case-mix systems enhances the transparency of performance and cost structure and can thus improve the quality of mental health care. We analysed a consecutive sample of 1677 inpatients with mental disorders from 11 hospitals using regression tree analysis. The model assigns patients to 17 groups, accounting for 17% of the variance for duration of stay. Patients with eating disorders had a longer duration of stay than patients with anxiety disorder, duration of mental illness of less than 3–5 years, lower levels of interpersonal problems and higher occupational position. The results showed that besides diagnosis, variables such as duration of illness and interpersonal problems are important for classifying inpatients with mental disorders. The results of the study should be critically reviewed regarding the empirical results of other studies and the appropriateness of case group concepts for inpatients with mental disorders.     

Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10⁻⁷ M) or continuously at an equivalent cumulative dose (6.6 × 10⁻⁹ M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.     

Functioning and disability 6–15 years after traumatic brain injuries in northern Sweden

Objectives –  To assess long‐term functioning and disability after traumatic brain injury (TBI). Material and methods –  Individuals (n = 88) in Norrbotten, northern Sweden, who had been transferred for neurosurgical care were assessed with internationally established TBI outcome measures 6–15 years post‐injury. Results –  There was an improvement in overall outcome from discharge from inpatient rehabilitation to follow‐up. Many individuals had a high degree of motor and cognitive functioning, which enabled them to live independently in their own home without assistance, but there remained a disability related to community reintegration and social participation. This affected their productivity and to some degree their marital stability. The remaining disability and reduced productivity were related to the age at injury and the injury severity. Conclusions –  Our data showed that individuals with a TBI can achieve and maintain a high degree of functioning many years after the injury. Increasing age and a greater injury severity contributed to their long‐term disability.     

Tooth movement and cytokines in gingival crevicular fluid and whole blood in growing and adult subjects.

INTRODUCTION: Tooth movement has been studied largely with respect to the force required for tipping when pressure distribution varies along the length of the periodontal ligament. But important factors for effective canine translation include the nature and magnitude of applied stress and the patient's cell biology. The purpose of this research was to test 3 hypotheses: (1) the velocity of tooth translation (v(t)) is related to applied stress and growth status, (2) a threshold of stress accounts for the lag phase, and (3) v(t) is correlated with the ratio (AI) of 2 cytokines (IL-1beta, IL-1RA) measured in gingival crevicular fluid (GCF) and stimulated whole blood (SWB). METHODS: Continuous maxillary canine retraction stresses of 13 kPa and 4, 26, or 52 kPa were applied bilaterally in 6 growing and 4 adult subjects for 84 days. Dental models and GCF samples were collected at 1- to 14-day intervals. Cytokines were measured in GCF and SWB cell cultures. RESULTS: V(t) was positively related to stress and was higher in growing subjects (P = .001). It was also related to AI(GCF) in growers (R2= 0.56) and nongrowers (R2= 0.72). Canines moved with 52 kPa showed a lag phase, and postlag phase AI(GCF) was twice that of lag phase AI(GCF). Mean v(t) and associated AI(GCF) during the postlag phase were nearly double the values for canines moved with 13 and 26 kPa. SWB production of cytokines was dose-dependent. For growing subjects, SWB IL-1RA was correlated with v(t) (R = 0.70-0.72), and AI(SWB) and IL-1beta concentrations were correlated with AI(GCF) (R = 0.73-0.78). CONCLUSIONS: V(t) varied with growth status and stresses < or = 52 kPa; stresses of < 52 kPa showed no lag phase; and equivalent stresses yielded subject-dependent differences in v(t), which correlated with cytokines in GCF and SWB.