We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state preference, with either fast or slow binding kinetics) and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e. g., a shift of the “”steady-state slow inactivation curve”), was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring GW3965 in vitro drugs were indistinguishable from slow-inactivated state-preferring drugs. On the other hand, fast-and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery,
respectively. The robustness of these observations was verified: i) by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii) by testing the same drugs in a fundamentally different model and iii) by an analysis of the effect of systematically changing www.selleckchem.com/products/SB-525334.html drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs
on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that conclusions based on voltage protocols that are used to detect slow-inactivated state preference are unreliable and should be re-evaluated.”
“We report photocurrent (PC) and its complemented
photoluminescence investigations of carrier escape dynamics in multi-layered InAs/GaAs self-assembled quantum selleck chemical dots (QDs) subjected to vertical electric fields. We found a nonlinear dependence of PC on the laser excitation power. This unusual behavior can be tuned by bias voltage. Very well agreement between PC data and theoretical prediction ensures that the accumulation of holes trapped in QDs is responsible for this nonlinearity. It is expected that this laser controlled electronic transport might open many potential applications in optoelectronic devices. (C) 2011 American Institute of Physics. [doi:10.1063/1.3562192]“
“Background: Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease leading to sensory and motor polyneuropathies, and functional limitations. Liver transplantation is the only treatment for FAP, requiring medication that negatively affects bone and muscle metabolism. The aim of this study was to compare body composition, levels of specific strength, level of physical disability risk, and functional capacity of transplanted FAP patients (FAPTx) with a group of healthy individuals (CON).
Methods: A group of patients with 48 FAPTx (28 men, 20 women) was compared with 24 CON individuals (14 men, 10 women). Body composition was assessed by dual-energy X-ray absorptiometry, and total skeletal muscle mass (TBSMM) and skeletal muscle index (SMI) were calculated.