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.     

The nonutility of chest roentgenographic examination in asymptomatic patients with positive tuberculin test results

To determine the value of chest roentgenograms in the management of asymptomatic persons with positive tuberculin skin test results, we undertook a retrospective review of all tests administered by our Employee Health Service, North Shore University Hospital, Manhasset, NY, between July 1, 1983 and November 1, 1987. Of 5200 tests, 247 results were positive. Two hundred twenty-one of these charts were reviewed for roentgenographic results and the presence of symptoms. All persons were asymptomatic. Chest roentgenograms revealed the following: normal, 188; unrelated abnormalities, 24; apical pleural thickening, 5; granulomas, 2; calcified hilar node, 1; and calcified node plus granuloma, 1. We noted no active tuberculosis, nor did the chest roentgenographic results influence recommendations for isoniazid prophylaxis. We conclude that chest roentgenograms are of value in 0% to 1.3% of asymptomatic people with positive tuberculin test results. A larger study should be undertaken to further define the usefulness of chest roentgenograms in this population.     

Brain serotonin transporter binding in non-depressed patients with Parkinson's disease

Early post-mortem data suggest that damage to brain serotonin neurones might play a role in some features (e.g., depression) of Parkinson's disease (PD). However, it is not known whether such damage is a typical characteristic of living patients with PD or whether the changes are regionally widespread. To address this question we measured, by positron emission tomography imaging, levels of the brain serotonin transporter (SERT), a marker for serotonin neurones, as inferred from binding of [¹¹C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB), a second generation SERT radioligand, in subcortical and cerebral cortical brain areas of clinically advanced non-depressed (confirmed by structured psychiatric interview) patients with PD. SERT binding levels in PD were lower than those in controls in all examined brain areas, with the changes statistically significant in orbitofrontal cortex (−22%), caudate (−30%), putamen (−26%), and midbrain (−29%). However, only a slight non-significant reduction (−7%) was observed in dorsolateral pre-frontal cortex, an area implicated in major depression. Our imaging data suggests that a modest, regionally widespread loss of brain serotonergic innervation might be a common feature of advanced PD. Further investigation will be required to establish whether SERT binding is more or less decreased in those patients with PD who also have major depressive disorder.     

Effects of intracerebral estradiol on the dorsal immobility response in the rat

The effects of intracerebral implants of 17 beta estradiol and cholesterol in five brain regions were tested on the duration of the dorsal immobility response in ovariectomized female rats. The dorsal immobility response was significantly prolonged by 4-hr implants of 17 beta estradiol in the dorsal striatum and nucleus accumbens, but not in the cortex, the globus pallidus, or the substantia nigra pars compacta. These data further support previous evidence that estradiol acts directly on the striatum to affect behavior in the rat.     

Zur Behandlung der Ohrblutgeschwulst

Ohne Zusammenfassung     

Wissenschaftliche Neurobildgebung in der Medizin

Neuroimaging has in recent years greatly contributed to our understanding of a wide range of aspects of central neurological diseases. These include the classification and localization of disease (e.g., in headache), the understanding of pathology (e.g., in Parkinson’s disease), mechanisms of reorganization (e.g., in stroke), and the subclinical progress of disease (e.g., in degenerative diseases). Apart form presurgical mapping, clinical applications of fMRI are limited. However, functional imaging enables the formulation of neurobiological hypotheses that can be tested clinically and is suited to test classical clinical hypotheses about how the brain works. Understanding the mechanisms and the site of pathology, e.g., in cluster headaches, will lead and has led to new therapeutic strategies. New methodological developments for neuroscientific applications are aimed at the integration of functional and morphological connectivity through a combination of magnetic resonance techniques (fMRI, DTI) and electrophysiological (EEG, MEG) recordings. In addition to stimulus-dependent activations, resting state activity has found increasing interest, for example, in sleep research and various psychiatric diseases (e.g., schizophrenia, borderline).     

High Caudal Epidural Anaesthesia with Local Anaesthetics or α2‐Agonists in Calves

The objective of this study was to examine the efficacy of a caudal epidural anaesthesia using lidocaine or xylazine in a high volume for analgesia of the flank, navel and hamstring tendon. Fourteen calves weighing 57.7 ± 5.1 kg and 37.9 ± 9.3 (mean ± SEM) days old were randomly divided into two groups of seven calves each. Calves belonging to the lidocaine group were given a 2% lidocaine solution in the sacrococcygeal vertebral space epidurally at a volume of 0.4 ml/kg (8 mg/kg) body weight (BW). Animals of the xylazine group were administered an epidural anaesthesia with xylazine at a dose of 0.1 mg/kg BW, diluted with a 0.9% saline solution to a corresponding final volume of 0.4 ml/kg BW. Heart rate and respiratory rate were measured and the degree and duration of analgesia was determined by the response to a skin prick with a hypodermic needle over a period of 350 min after epidural injection. After epidural anaesthesia with lidocaine the mean heart rate increased during dorsal recumbency, whereas after xylazine both heart rate and respiratory rate decreased significantly (P < 0.05). The epidural injection of xylazine compared with lidocaine caused longer (P < 0.05) analgesia at the hamstring tendon (mean ± SEM, 120.7 ± 29.7 min versus 93.6 ± 3.5 min) and at the flank (100.7 ± 24.4 min versus 78.3 ± 11.1 min). There were no differences in the intensity of analgesia between groups. After xylazine application analgesia at the navel was achieved for 95.0 ± 14.1 min whereas after lidocaine injection sufficient analgesia at the navel was found in just two of seven calves for 55 and 95 min respectively. Based on above experiences, a second study was performed, in which a combination of xylazine and local anaesthetics was used and the injection volume was increased to prove the efficacy of caudal epidural anaesthesia in 15 calves (26.3 ± 26.7 days; 57.1 ± 19.5 kg) submitted to the clinic for regular umbilical surgery. In these cases the xylazine (0.1 mg/kg BW) was diluted with 2% lidocaine (n = 7) or 2% procaine (n = 8) to a corresponding final volume of 0.5–0.6 ml/kg BW. In all cases complete anaesthesia of the surgical area was achieved and no adverse effects were observed. Overall the high volume caudal epidural anaesthesia represents an effective, safe, cheap and easy to perform alternative for anaesthesia of the navel, flank and hamstring tendon in calves without major side effects.     

ES05ROUTINE PARAFIBROMIN IMMUNOHISTOCHEMISTRY OF LARGE PARATHYROID ADENOMAS IS NOT AN EFFECTIVE SCREENING STRATEGY FOR CARCINOMA

Purpose Parathyroid carcinoma (PC) is rare and accounts for less than 1% of all cases of primary hyperparathyroidism (PHPT). The definitive histopathologic diagnosis of PC requires unequivocal invasion or metastasis which may be absent at first presentation. As a result, many cases of PC can only be diagnosed retrospectively. Parafibromin is the protein encoded by HRPT2 which is mutated and not expressed in many parathyroid carcinomas. Given that PCs generally weigh more than parathyroid adenomas (PA)s, we hypothesized that amongst large PAs there may be a high incidence of occult PC which could be identified by negative staining for parafibromin. Methodology 57 parathyroid glands weighing greater than 2 grams excised from 1998–2006 were identified from the University of Sydney Endocrine Surgical Database. Two specimens with a histopathologic diagnosis of PC were excluded. Immunohistochemical staining for parafibromin was performed on the remaining 55 PAs. Results Of the 55 specimens stained for parafibromin only one definite negative stain was detected. This case was originally classified as an “atypical adenoma” because it showed nuclear and architectural atypia without unequivocal evidence of invasive growth. In view of the negative staining for parafibromin it therefore probably represents occult carcinoma. There has been no evidence of recurrence or metastasis after 6.5 years. Conclusions Complete loss of staining for parafibromin is very rare in giant parathyroid adenomas suggesting that occult carcinoma is equally rare. As a result routine immunohistochemical staining for parafibromin does not appear to be an effective screening test for carcinoma in large PA without histopathologic features of PC.