Fast lidocaine block of cardiac and skeletal muscle sodium channels: one site with two routes of access

We have studied the block by lidocaine and its quaternary derivative, QX-314, of single, batrachotoxin (BTX)-activated cardiac and skeletal muscle sodium channels incorporated into planar lipid bilayers. Lidocaine and QX-314, applied to the intracellular side, appear to induce incompletely resolved, rapid transitions between the open and the blocked state of BTX-activated sodium channels from both heart and skeletal muscle. We used amplitude distribution analysis (Yellen, G. 1984. J. Gen. Physiol. 84:157–186.) to estimate the rate constants for block and unblock. Block by lidocaine and QX-314 from the cytoplasmic side exhibits rate constants with similar voltage dependence. The blocking rate increases with depolarization, and the unblocking rate increases with hyperpolarization. Fast lidocaine block was virtually identical for sodium channels from skeletal (rat, sheep) and cardiac (beef, sheep) muscle. Lidocaine block from the extracellular side occurred at similar concentrations. However, for externally applied lidocaine, the blocking rate was voltage-independent, and was proportional to concentration of the uncharged, rather than the charged, form of the drug. In contrast, unblocking rates for internally and externally applied lidocaine were identical in magnitude and voltage dependence. Our kinetic data suggest that lidocaine, coming from the acqueous phase on the cytoplasmic side in the charged form, associates and dissociates freely with the fast block effector site, whereas external lidocaine, in the uncharged form, approaches the same site via a direct, hydrophobic path

Laser powder bed fusion of porous graded structures: a comparison between computational and experimental analysis

Functionally graded porous structures (FGPSs) are gaining interest in the biomedical sector, specifically for orthopaedic implants. In this study, the compressive behaviour of seven different FGPSs comprised of Face Centred Cubic (FCC) and the Octet truss unit cells (OCT) were analysed. The porosity of the structures were graded in different directions (radially, longitudinally, laterally and longitudinally & radially) by varying the strut diameters or by combining the two types of unit cells. The structures were manufactured by laser power bed fusion and compression tests were performed. Radially and laterally porous graded structures were found to outperform uniform porous structures with an increase in stiffness of 13.7% and 21.1% respectively. The experimental and finite element analysis (FEA) results were in good agreement with differences in elastic modulus of 9.4% and yield strength of 15.8%. A new FEA beam model is proposed in this study to analyse this type of structures with accurate results and the consequent reduction of computational time. The accuracy of the Kelvin-Voight model and the rule of mixtures for predicting the mechanical behaviour of different FGPSs was also investigated. The results demonstrate the adequacy of the analytical models specifically for hybrid structures and for structures with smooth diameter transitions

Purification of a lectin from Eugenia uniflora L. seeds and its potential antibacterial activity

Aims: The aim of this work was to analyse the antimicrobial properties of a purified lectin from Eugenia uniflora L. seeds. Methods and Results: The E. uniflora lectin (EuniSL) was isolated from the seed extract and purified by ion-exchange chromatography in DEAE-Sephadex with a purification factor of 11·68. The purified lectin showed a single band on denaturing electrophoresis, with a molecular mass of 67 kDa. EuniSL agglutinated rabbit and human erythrocytes with a higher specificity for rabbit erythrocytes. The haemagglutination was not inhibited by the tested carbohydrates but glycoproteins exerted a strong inhibitory action. The lectin proved to be thermo resistant with the highest stability at pH 6·5 and divalent ions did not affect its activity. EuniSL demonstrated a remarkable nonselective antibacterial activity. EuniSL strongly inhibited the growth of Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella sp. with a minimum inhibitory concentration (MIC) of 1·5 μg ml−1, and moderately inhibited the growth of Bacillus subtilis, Streptococcus sp. and Escherichia coli with a MIC of 16·5 μg ml−1. Conclusions: EuniSL was found to be effective against bacteria. Significance and Impact of the Study: The strong antibacterial activity of the studied lectin indicates a high potential for clinical microbiology and therapeutic applications.VALNATURA of ALFA Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq

Auswirkung der Paraffinmigration auf die freie Oberflächenenergie von Naturkautschuk

Die Auswirkung der Migration von Paraffinwachs auf die freie Oberflächenenergie (Oberflächenspannung) von Naturkautschuk (NR) wurde untersucht. Dazu wurde das Wachs in den Kautschuk eingemischt und die Proben anschließend bis zu 168 h bei Raumtemperatur gelagert, bevor die Oberflächenspannung durch Kontaktwinkelmessungen bestimmt wurde. Mit Hilfe der Sekundärionen-Massenspektrometrie wurden”chemische Fingerabdrücke” der Kautschukoberflächen erstellt. Die Oberflächenspannung verringerte sich mit zunehmender Lagerzeit aufgrund der Wanderung des Wachses an die Oberfläche. Die rascheste Abnahme erfolgte innerhalb der ersten 3 h. Danach verringerte sich die Oberflächenspannung sehr viel langsamer und erreichte nach 48-stündiger Lagerung ein Plateau. Durch die Migration des Wachses an die Oberfläche verringerte sich die Oberflächenspannung insgesamt um ca. 46 %. Die Verringerung der Oberflächenspannung beeinflusst nachteilig die Möglichkeit des Kautschuks zur Bindung mit sich selbst oder mit anderen Elastomeren. The effect of the migration of paraffin wax on the surface free energy of natural rubber (NR) was investigated. The rubber was mixed with the wax and then stored at ambient temperature for up to 168 hrs before its surface free energy was measured using contact angle measurement. Static secondary ion mass spectrometry was also used to provide a chemical fingerprint of the rubber surfaces. The surface free energy decreased as a function of storage time because of the migration of the wax to the rubber surface. The highest rate of reduction was recorded up to 3 hrs and thereafter, the surface free energy decreased at a much slower rate, reaching a plateau after 48 hrs in storage. In total, the surface free energy reduced by approximately 46 % as a result of the migration of the wax to the rubber surface. The reduction in surface free energy could adversely affect ability of the rubber to stick to itself and to other dissimilar elastomers

Atmospheric Heating and Wind Acceleration: Results for Cool Evolved Stars based on Proposed Processes

A chromosphere is a universal attribute of stars of spectral type later than ~F5. Evolved (K and M) giants and supergiants (including the zeta Aurigae binaries) show extended and highly turbulent chromospheres, which develop into slow massive winds. The associated continuous mass loss has a significant impact on stellar evolution, and thence on the chemical evolution of galaxies. Yet despite the fundamental importance of those winds in astrophysics, the question of their origin(s) remains unsolved. What sources heat a chromosphere? What is the role of the chromosphere in the formation of stellar winds? This chapter provides a review of the observational requirements and theoretical approaches for modeling chromospheric heating and the acceleration of winds in single cool, evolved stars and in eclipsing binary stars, including physical models that have recently been proposed. It describes the successes that have been achieved so far by invoking acoustic and MHD waves to provide a physical description of plasma heating and wind acceleration, and discusses the challenges that still remain.Comment: 46 pages, 9 figures, 1 table; modified and unedited manuscript; accepted version to appear in: Giants of Eclipse, eds. E. Griffin and T. Ake (Berlin: Springer

Calibration of Super-Kamiokande Using an Electron Linac

In order to calibrate the Super-Kamiokande experiment for solar neutrino measurements, a linear accelerator (LINAC) for electrons was installed at the detector. LINAC data were taken at various positions in the detector volume, tracking the detector response in the variables relevant to solar neutrino analysis. In particular, the absolute energy scale is now known with less than 1 percent uncertainty.Comment: 24 pages, 16 figures, Submitted to NIM

Insulin Glargine in the Intensive Care Unit: A Model-Based Clinical Trial Design

Online 4 Oct 2012Introduction: Current succesful AGC (Accurate Glycemic Control) protocols require extra clinical effort and are impractical in less acute wards where patients are still susceptible to stress-induced hyperglycemia. Long-acting insulin Glargine has the potential to be used in a low effort controller. However, potential variability in efficacy and length of action, prevent direct in-hospital use in an AGC framework for less acute wards. Method: Clinically validated virtual trials based on data from stable ICU patients from the SPRINT cohort who would be transferred to such an approach are used to develop a 24-hour AGC protocol robust to different Glargine potencies (1.0x, 1.5x and 2.0x regular insulin) and initial dose sizes (dose = total insulin over prior 12, 18 and 24 hours). Glycemic control in this period is provided only by varying nutritional inputs. Performance is assessed as %BG in the 4.0-8.0mmol/L band and safety by %BG<4.0mmol/L. Results: The final protocol consisted of Glargine bolus size equal to insulin over the previous 18 hours. Compared to SPRINT there was a 6.9% - 9.5% absolute decrease in mild hypoglycemia (%BG<4.0mmol/L) and up to a 6.2% increase in %BG between 4.0 and 8.0mmol/L. When the efficacy is known (1.5x assumed) there were reductions of: 27% BG measurements, 59% insulin boluses, 67% nutrition changes, and 6.3% absolute in mild hypoglycemia. Conclusion: A robust 24-48 clinical trial has been designed to safely investigate the efficacy and kinetics of Glargine as a first step towards developing a Glargine-based protocol for less acute wards. Ensuring robustness to variability in Glargine efficacy significantly affects the performance and safety that can be obtained