Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness?

Bailey DM, Taudorf S, Berg RMG, Lundby C, McEneny J, Young IS, Evans KA, James PE, Shore A, Hullin DA, McCord JM, Pedersen BK, Moller K. Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness? Am J Physiol Regul Integr Comp Physiol 297: R1283-R1292, 2009. First published September 2, 2009; doi: 10.1152/ajpregu.00366.2009.-This study examined whether hypoxia causes free radical-mediated disruption of the blood-brain barrier (BBB) and impaired cerebral oxidative metabolism and whether this has any bearing on neurological symptoms ascribed to acute mountain sickness (AMS). Ten men provided internal jugular vein and radial artery blood samples during normoxia and 9-h passive exposure to hypoxia (12.9% O-2). Cerebral blood flow was determined by the Kety-Schmidt technique with net exchange calculated by the Fick principle. AMS and headache were determined with clinically validated questionnaires. Electron paramagnetic resonance spectroscopy and ozone-based chemiluminescence were employed for direct detection of spin-trapped free radicals and nitric oxide metabolites. Neuron-specific enolase (NSE), S100 beta, and 3-nitrotyrosine (3-NT) were determined by ELISA. Hypoxia increased the arterio-jugular venous concentration difference (a-v(D)) and net cerebral output of lipid-derived alkoxyl-alkyl free radicals and lipid hydroperoxides (P

KCNQ Currents and Their Contribution to Resting Membrane Potential and the Excitability of Interstitial Cells of Cajal From the Guinea Pig Bladder

PURPOSE: The presence of novel KCNQ currents was investigated in guinea pig bladder interstitial cells of Cajal and their contribution to the maintenance of the resting membrane potential was assessed. MATERIALS AND METHODS: Enzymatically dispersed interstitial cells of Cajal were patch clamped with K(+) filled pipettes in voltage clamp and current clamp modes. Pharmacological modulators of KCNQ channels were tested on membrane currents and the resting membrane potential. RESULTS: Cells were stepped from -60 to 40 mV to evoke voltage dependent currents using a modified K(+) pipette solution containing ethylene glycol tetraacetic acid (5 mM) and adenosine triphosphate (3 mM) to eliminate large conductance Ca activated K channel and K(adenosine triphosphate) currents. Application of the KCNQ blockers XE991, linopirdine (Tocris Bioscience, Ellisville, Missouri) and chromanol 293B (Sigma) decreased the outward current in concentration dependent fashion. The current-voltage relationship of XE991 sensitive current revealed a voltage dependent, outwardly rectifying current that activated positive to -60 mV and showed little inactivation. The KCNQ openers flupirtine and meclofenamic acid (Sigma) increased outward currents across the voltage range. In current clamp mode XE991 or chromanol 293B decreased interstitial cell of Cajal resting membrane potential and elicited the firing of spontaneous transient depolarizations in otherwise quiescent cells. Flupirtine or meclofenamic acid hyperpolarized interstitial cells of Cajal and inhibited any spontaneous electrical activity. CONCLUSIONS: This study provides electrophysiological evidence that bladder interstitial cells of Cajal have KCNQ currents with a role in the regulation of interstitial cell of Cajal resting membrane potential and excitability. These novel findings provide key information on the ion channels present in bladder interstitial cells of Cajal and they may indicate relevant targets for the development of new therapies for bladder instability.

Coordinated control of DFIG’s rotor and grid side converters during network unbalance

This paper proposes a coordinated control of the rotor and grid side converters (RSC & GSC) of doubly-fed induction generator (DFIG) based wind generation systems under unbalanced voltage conditions. System behaviors and operations of the RSC and GSC under unbalanced voltage are illustrated. To provide enhanced operation, the RSC is controlled to eliminate the torque oscillations at double supply frequency under unbalanced stator supply. The oscillation of the stator output active power is then cancelled by the active power output from the GSC, to ensure constant active power output from the overall DFIG generation system. To provide the required positive and negative sequence currents control for the RSC and GSC, a current control strategy containing a main controller and an auxiliary controller is analyzed. The main controller is implemented in the positive (dq)+ frame without involving positive/negative sequence decomposition whereas the auxiliary controller is implemented in the negative sequence (dq)? frame with negative sequence current extracted. Simulation results using EMTDC/PSCAD are presented for a 2MW DFIG wind generation system to validate the proposed control scheme and to show the enhanced system operation during unbalanced voltage supply.

A fast multi-output RBF neural network construction method

This paper investigates the center selection of multi-output radial basis function (RBF) networks, and a multi-output fast recursive algorithm (MFRA) is proposed. This method can not only reveal the significance of each candidate center based on the reduction in the trace of the error covariance matrix, but also can estimate the network weights simultaneously using a back substitution approach. The main contribution is that the center selection procedure and the weight estimation are performed within a well-defined regression context, leading to a significantly reduced computational complexity. The efficiency of the algorithm is confirmed by a computational complexity analysis, and simulation results demonstrate its effectiveness. (C) 2010 Elsevier B.V. All rights reserved.