Neuronal voltage-gated sodium channel subtypes: Key roles in inflammatory and neuropathic pain

Voltage-gated sodium channels (VGSCs) play an important role in neuronal excitability. Regulation of VGSC activity is a complex phenomenon that occurs at multiple levels in the cell, including transcriptional regulation, post-translational modification and membrane insertion and retrieval. Multiple VGSC subtypes exist that vary in their biophysical and pharmacological properties and tissue distribution. Any alteration of the VGSC subtype profile of a neuron or the mechanisms that regulate VGSC activity can cause significant changes in neuronal excitability. Inflammatory and neuropathic pain states are characterised by alterations in VGSC subtype composition and activity in sensory neurons. This review focuses on the VGSC subtypes involved in such pain states. (c) 2006 Elsevier Ltd. All rights reserved

The glia response after peripheral nerve injury: A comparison between Schwann cells and olfactory ensheathing cells and their uses for neural regenerative therapies

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory nerve, and Schwann cells (SCs), which are present in the rest of the PNS. These two glial types share many similar morphological and functional characteristics but also exhibit key differences. The olfactory nerve is constantly turning over throughout life, which means OECs are continuously stimulating neural regeneration, whilst SCs only promote regeneration after direct injury to the PNS. This review presents a comparison between these two PNS systems in respect to normal physiology, developmental anatomy, glial functions and their responses to injury. A thorough understanding of the mechanisms and differences between the two systems is crucial for the development of future therapies using transplantation of peripheral glia to treat neural injuries and/or disease.Griffith Health, School of Nursing and MidwiferyFull Tex

Assessment of the Food-Swallowing Process Using Bolus Visualisation and Manometry Simultaneously in a Device that Models Human Swallowing

The characteristics of the flows of boluses with different consistencies, i.e. different rheological properties, through the pharynx have not been fully elucidated. The results obtained using a novel in vitro device, the Gothenburg Throat, which allows simultaneous bolus flow visualisation and manometry assessments in the pharynx geometry, are presented, to explain the dependence of bolus flow on bolus consistency. Four different bolus consistencies of a commercial food thickener, 0.5, 1, 1.5 and 2\ua0Pa\ua0s (at a shear rate of 50\ua0s −1 )—corresponding to a range from low honey-thick to pudding-thick consistencies on the National Dysphagia Diet (NDD) scale—were examined in the in vitro pharynx. The bolus velocities recorded in the simulator pharynx were in the range of 0.046–0.48\ua0m/s, which is within the range reported in clinical studies. The corresponding wall shear rates associated with these velocities ranged from 13\ua0s −1 (pudding consistency) to 209\ua0s −1 (honey-thick consistency). The results of the in vitro manometry tests using different consistencies and bolus volumes were rather similar to those obtained in clinical studies. The in vitro device used in this study appears to be a valuable tool for pre-clinical analyses of thickened fluids. Furthermore, the results show that it is desirable to consider a broad range of shear rates when assessing the suitability of a certain consistency for swallowing

Simultaneous X-ray Video-Fluoroscopy and Pulsed Ultrasound Velocimetry Analyses of the Pharyngeal Phase of Swallowing of Boluses with Different Rheological Properties

The Ultrasound Velocity Profiling (UVP) technique allows real-time, non-invasive flow mapping of a fluid along a 1D-measuring line. This study explores the possibility of using the UVP technique and X-ray video-fluoroscopy (XVF) to elucidate the deglutition process with the focus on bolus rheology. By positioning the UVP probe so that the pulsed ultrasonic beam passes behind the air-filled trachea, the bolus flow in the pharynx can be measured. Healthy subjects in a clinical study swallowed fluids with different rheological properties: Newtonian (constant shear viscosity and non-elastic); Boger (constant shear viscosity and elastic); and shear thinning (shear rate-dependent shear viscosity and elastic). The results from both the UVP and XVF reveal higher velocities for the shear thinning fluid, followed by the Boger and the Newtonian fluids, demonstrating that the UVP method has equivalent sensitivities for detecting the velocities of fluids with different rheological properties. The velocity of the contraction wave that clears the pharynx was measured in the UVP and found to be independent of bolus rheology. The results show that UVP not only assesses accurately the fluid velocity in a bolus flow, but it can also monitor the structural changes that take place in response to a bolus flow, with the added advantage of being a completely non-invasive technique that does not require the introduction of contrast media

Gamma radiolytic stability of CyMe4BTBP and the effect of nitric acid

The highly selective nitrogen donor ligand CyMe4BTBP for An(III) separation by solvent extraction was irradiated in a 60Co γ-source under varying conditions. Organic solutions of 10 mmol/L ligand in 1-octanol were contacted with different concentrations of nitric acid to observe the influence of an aqueous phase during irradiation. In subsequent liquid-liquid extraction experiments, distribution ratios of 241Am and 152Eu were determined. Distribution ratios decreased with increasing absorbed dose when irradiation was performed in the absence of nitric acid. With addition of nitric acid, initial distribution ratios remained constant over the whole examined dose range up to 300 kGy. For qualitative determination of radiolysis products, HPLC-MS measurements were performed. The protective effect of nitric acid was confirmed, since in samples irradiated with acid contact, no degradation products were observed, but only addition products of the 1-octanol molecule to the CyMe4BTBP molecule

Gamma radiolytic stability of CyMe4BTBP and the effect of nitric acid

The highly selective nitrogen donor ligand CyMe4BTBP for An(III) separation by solvent extraction was irradiated in a 60Co γ-source under varying conditions. Organic solutions of 10 mmol/L ligand in 1-octanol were contacted with different concentrations of nitric acid to observe the influence of an aqueous phase during irradiation. In subsequent liquid-liquid extraction experiments, distribution ratios of 241Am and 152Eu were determined. Distribution ratios decreased with increasing absorbed dose when irradiation was performed in the absence of nitric acid. With addition of nitric acid, initial distribution ratios remained constant over the whole examined dose range up to 300 kGy. For qualitative determination of radiolysis products, HPLC-MS measurements were performed. The protective effect of nitric acid was confirmed, since in samples irradiated with acid contact, no degradation products were observed, but only addition products of the 1-octanol molecule to the CyMe4BTBP molecule

Posterior cricoid region fluoroscopic findings: the posterior cricoid plication.

The region posterior to the cricoid cartilage is challenging to assess fluoroscopically. The purpose of this investigation is to critically evaluate the posterior cricoid (PC) region on fluoroscopy and describe patterns of common findings. This was a case control study. All fluoroscopic swallowing studies performed between June 16, 2009, and February 9, 2010, were reviewed for features seen in the PC region. These findings were categorized into distinct patterns and compared to fluoroscopic studies performed in a cohort of normal volunteers. Two hundred patient studies and 149 healthy volunteer studies were reviewed. The mean age of the referred patient cohort and the volunteer cohort was 57 years (±19) and 61 years (±16), respectively (p > 0.05). The patient cohort was 53% male and the control cohort was 56% female (p > 0.05). Four groups were identified. Pharyngoesophageal webs were seen in 7% (10/149) of controls and 14% (28/200) of patients (p = 0.03). A PC arch impression was seen in 16% of patients (32/200) and controls (24/149) (p = 1). A PC plication was demonstrated in 23% (34/149) of controls and 30% (60/200) of patients (p = 0.13). No distinctive PC region findings were seen in 54% (81/149) of controls and 42% (84/200) of referred patients (p = 0.02). Four patients (2%) had both a web and a PC plication. Four categories of PC region findings were identified (unremarkable PC region, web, PC arch impression, and PC plication). Both patients referred for swallowing studies and healthy volunteers demonstrated esophageal webs, PC arch impressions, and PC plications. Only webs were more common in patients than in control subjects (p = 0.03). The PC impression and PC plication are likely to represent normal variants that may be identified on fluoroscopic swallow studies

Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin

Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society

The Qualified Legal Compliance Committee: Using the Attorney Conduct Rules to Restructure the Board of Directors

The Securities and Exchange Commission introduced a new corporate governance structure, the qualified legal compliance committee, as part of the professional standards of conduct for attorneys mandated by the Sarbanes-Oxley Act of 2002. QLCCs are consistent with the Commission\u27s general approach to improving corporate governance through specialized committees of independent directors. This Article suggests, however, that assessing the benefits and costs of creating QLCCs may be more complex than is initially apparent. Importantly, QLCCs are unlikely to be effective in the absence of incentives for active director monitoring. This Article concludes by considering three ways of increasing these incentives