The ubiquitin-proteasome pathway in health and disease of the nervous system

In recent years, proteolysis by the ubiquitin-proteasome pathway has attained prominence as a new molecular mechanism that regulates many vital functions of the nervous system, including development of synaptic connections and synaptic plasticity. Here, we review the latest findings on the role of proteolysis in sculpting the nervous system through control of axonal growth, axonal and dendritic pruning, and regulation of synaptic size and number. We also discuss how protein degradation functions in synaptic plasticity and the roles of local proteolysis in neuronal compartments. In addition, we describe how proteolysis is associated with Alzheimer's disease and ataxia. Furthermore, we highlight the recent approaches that exploit components of the ubiquitin-proteasome pathway for amelioration of these diseases in animal models.     

Multiple fourth ventricular hydatidosis

Hydatid disease caused by ingestion of eggs of the cestode Echinococcus granulosus is endemic in the Middle East, Mediterranean countries, South America, North Africa and Australia.¹ Infratentorial occurrence of hydatid cyst is rare. We present a report of an extremely rare case of multiple exclusive fourth ventricular hydatid cysts, both primary and secondary, and discuss problems with the diagnosis and management of this condition.     

Isolation,structural determination,synthesis and quantitative determination of impurities in Intron-A,leached from a silicone tubing

Investigation of unexpected levels of impurities in Intron product has revealed the presence of low levels of impurities leached from the silicone tubing (Rehau RAU-SIK) on the Bosch filling line. In order to investigate the effect of these compounds (1a, 1b and 2) on humans, they were isolated identified and synthesized. They were extracted from the tubing by stirring in Intron placebo at room temperature for 72 h and were enriched on a reverse phase CHP-20P column, eluting with gradient aqueous ACN and were separated by HPLC. Structural elucidation of 1a, 1b and 2 by MS and NMR studies demonstrated them to be halogenated biphenyl carboxylic acids. The structures were confirmed by independent synthesis. Levels of extractable impurities in first filled vials of actual production are estimated to be in the range of 0.01–0.55 μg/vial for each leached impurity. Potential toxicity of these extractables does not represent a risk for patients under the conditions of clinical use.     

Prospective evaluation of the learning curve for holmium laser enucleation of the prostate

PURPOSE: In a prospective manner we evaluated the learning experience of an endourologist inexperienced with holmium laser prostate enucleation and its impact on surgical outcome. We also reviewed the literature to document technical features of holmium laser prostate enucleation at different institutions. MATERIALS AND METHODS: Patient demographic, perioperative and followup data were analyzed. To assess the impact of the learning curve on postoperative outcome patients were divided into group 1--patients 1 to 50, group 2--51 to 100 and group 3--101 to 162. The effect of the learning curve and weight of resected tissue on enucleation and morcellation efficiency was studied. RESULTS: Holmium laser prostate enucleation was successfully completed in 93.82% of patients. Eight patients required conversion to transurethral prostate resection. Enucleation and morcellation efficiency was 0.49 and 2.75 gm per minute, respectively. Enucleation efficiency attained a plateau after 50 cases. Postoperative outcome was compared in the 3 patient groups. There was a higher incidence of capsular perforation and stenotic urethral complications in group 1. In the literature a mean of 57.09% of tissue (range -9.6 to 81.9%) was retrieved after holmium laser prostate enucleation and mean efficiency was 0.52 gm per minute (range -0.11 to 1.09). Efficiency increased proportionally with resected prostate weight. CONCLUSIONS: An endourologist inexperienced with holmium laser prostate enucleation can perform the procedure with reasonable efficiency after about 50 cases with an outcome comparable to that of experts, as described in the literature. During the learning curve conversion to transurethral prostate resection can be done without any harm to the patient.     

Primary non-Hodgkin's B-cell lymphoma of the male urethra presenting as stricture disease

Primary urethral lymphoma is exceedingly rare. There are only three cases reported involving the male urethra, with one in an immunocompromised man. We report a case of primary B-cell lymphoma presenting as complex urethral stricture disease.     

Phase synchronization of the ongoing EEG and auditory EP generation.

OBJECTIVE: We investigated the role of phase synchronization of the spontaneous electroencephalogram (EEG) in auditory evoked potential (EP) generation in a sample of healthy individuals. METHODS: Auditory responses were obtained from 20 healthy subjects following a double stimulus paradigm, using two identical tone bursts (S1 and S2) separated by 0.5s. Single-trial auditory evoked potentials were decomposed into sinusoidal, exponentially decaying/increasing components using the piecewise Prony method (PPM). Pre- and post-stimulus phase histograms were compared to determine the degree of phase synchronization produced by auditory stimulation. RESULTS: Analysis of single responses revealed that the S1 stimuli produced phase synchronization in the 2-8Hz frequency range, with little or no concomitant amplitude increase. A significantly reduced phase effect was seen in response to S2 stimuli. CONCLUSIONS: Stimulus-induced phase synchronization of the ongoing EEG is a major mechanism for the generation of auditory EP components with a latency in the 50-250ms range. SIGNIFICANCE: The fact that the EP components accessed here are generated through phase synchronization implies that the ensemble-averaged EP will not resemble the single trial response, and it would certainly be misleading to consider the single trial response as an amplitude-scaled version of the ensemble average.     

Real-time multiplex PCR assay for rapid detection and toxintyping of Clostridium perfringens toxin producing strains in feces of dairy cattle

Clostridium perfringens is an anaerobic, gram-positive, spore-forming bacterium associated with a wide variety of diseases in domestic animals and humans. We have developed dual-labeled fluorescence hybridization probe (TaqMan((R)))-based real-time multiplex PCR assay for detection of toxin genes alpha (cpa), beta (cpb), iota (ia), epsilon (etx), beta2 (cpb2) and enterotoxin (cpe) of C. perfringens directly from cattle feces. The assay was standardized using ATCC reference strains of C. perfringens producing alpha, beta, iota, epsilon and enterotoxin, respectively. The assay for detection of beta2 toxin gene was standardized using a field strain of C. perfringens producing beta2 toxin. The minimum detection limit for the real time PCR assay ranged from 5 to 70 pg of DNA for the six toxin genes. A total of 307 fecal samples collected from seven dairy herds in Pennsylvania were analyzed using the multiplex assay. The real-time PCR assay revealed that cpa, cpb, ia, etx, cpb2 and cpe were detected in 68 (28.2%), 6 (2.5%), 6 (2.5%), 4 (1.6%), 164 (68%) and 11 (4.5%) of 241 PCR positive samples, respectively. The findings of the study revealed that C. perfringens beta2 toxin producing strains were widely prevalent in lactating cows in Pennsylvania and they may play an important role in C. perfringens associated diarrheal diseases.