Effects of U-50,488H on scopolamine-, mecamylamine- and dizocilpine-induced learning and memory impairment in rats

The role of kappa opioid receptor agonists in learning and memory is controversial. In the present study, the effects of U-50,488H on scopolamine-, mecamylamine- and dizocilpine-induced learning and memory impairments in rats were investigated. Scopolamine (3.3 mumol/kg s.c.), a muscarinic cholinergic antagonist, and mecamylamine (40 mumol/kg s.c.), a nicotinic cholinergic antagonist, significantly impaired learning and memory in rats in a step-through type passive avoidance test. Administration of U-50,488H (0.17 or 0.51 mumol/kg s.c.) 25 min before the acquisition trial reversed the impairment of learning and memory induced by scopolamine and mecamylamine. Although low doses of scopolamine (0.17 mumol/kg) and mecamylamine (12 mumol/kg) had no effect, concurrent administration of both antagonists induced impairment of learning and memory. Scopolamine significantly increased acetylcholine release in the hippocampus as determined by in vivo brain microdialysis. On the other hand, mecamylamine significantly decreased acetylcholine release. U-50,488H completely blocked the decrease in acetylcholine release induced by mecamylamine, whereas it only partially blocked the increase of acetylcholine induced by scopolamine. On the other hand, an endogenous kappa opioid receptor agonist, dynorphin A (1-13), did not block the increase in acetylcholine release induced by scopolamine. The antagonistic effect of U-50,488H was abolished by pretreatment with nor-binaltorphimine (4.9 nmol/rat i.c.v.), a selective kappa opioid receptor antagonist. U-50,488H did not affect the impairment of learning and memory induced by the blockade of NMDA receptors by dizocilpine ((+)-MK-801). These results suggest that U-50,488H reverses the impairment of learning and memory induced by the blockade of cholinergic transmission and abolishes the decrease of acetylcholine release induced by mecamylamine via the kappa receptor-mediated opioid neuronal system.     

An analysis of the intracerebral ability to eliminate a nitroxide radical in the rat after administration of idebenone by anin vivo rapid scan electron spin resonance spectrometer

Electron spin resonance (ESR) measurements after intracerebroventricular injection of a nitroxide radical were carried out in rats (n=6) that received oral idebenone for 2 weeks and in control rats (n=5), using anin vivo rapid scan ESR spectrometer. The half-life of nitroxide, which was estimated from the change in the peak height (M=+1) of the ESR signals from the head, was used as a marker for the elimination of the nitroxide radical. The half-life in the rats treated with idebenone was significantly shorter than it was in the controls (p<0.05). This finding indicates that the treatment with idebenone can enhance the intracerebral-eliminating ability of the nitroxide radical.     

A genetic animal model of human neocortical heterotopia associated with seizures

Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a "rim-to-core" neurogenetic pattern rather than the characteristic "inside-out" pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the tish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures. The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.     

Design and synthesis of oligosaccharides that interfere with glycoprotein quality-control systems

Calnexin (CNX) and its soluble homologue calreticulin (CRT) are lectin-like molecular chaperones that help newly synthesized glycoproteins to fold correctly in the rough endoplasmic reticulum (ER). To investigate the mechanism of glycoprotein-quality control, we have synthesized structurally defined high-mannose-type oligosaccharides related to this system. This paper describes the synthesis of the non-natural undecasaccharide 2 and heptasaccharide 16, designed as potential inhibitors of the ER quality-control system. Each possesses the key tetrasaccharide element (Glc1Man3) critical for the CNX/CRT binding, while lacking the pentamannosyl branch required for glucosidase II recognition. These oligosaccharides were evaluated for their ability to bind CRT by isothermal titration calorimetry (ITC). As expected, each of them had a significant affinity towards CRT. In addition, these compounds were shown to be resistant to glucosidase II digestion. Their activities in blocking the chaperone function of CRT were next measured by using malate dehydrogenase (MDH) as a substrate. Their inhibitory effects were shown to correlate well with their CRT-binding affinities, both being critically dependent upon the presence of the terminal glucose (Glc) residue.     

PERFORMANCE OF A PRESSURIZED TWO-STAGE FLUIDIZED GASIFICATION PROCESS FOR PRODUCTION OF LOW-BTU GAS FROM COAL CHAR

A two-stage pressurized fluidized-bed gasification process has been developed to produce low-heating value gases from coal char. The reactor was 0.075 m id. and 1.4 m long, and gasification experiments were conducted under pressures up to 790 kPa and at temperatures up to 1323 K. A partition disc was used to divide the fluidized bed into two stages, using the first stage as a partial combuster and gasifier and the second stage as a gasifier. The disc was designed to control compositions of coal char particles in both stages so that the heat required for the endothermic gasification reaction in the second stage can be provided by the heat of combustion in the first

For conditions examined here, the disc with an opening ratio of 40° was found to give optimum distribution of the char particles in both stages without ash agglomeration. It was also shown that all oxygen gas was completely consumed within the first stage

The heating value of the product gas increased with the char feed rale. However, there may be an oplimum Teed ratio of char and sand-particles since the higher char feed rate causes more frequent ash agglomeration as well as less carbon conversion     

Solid-state source of atomic oxygen for low-temperature oxidation processes: application to pulsed laser deposition of TiO2:N films

An atomic oxygen (AO) source has been redesigned to coordinate with a pulsed laser deposition system and used to grow nitrogen-doped TiO(2) films by deposition of TiN and simultaneous irradiation of the substrate with AO. The AO source uses an incandescently heated thin tube of zirconia as an oxygen permeation media to generate pure AO of low kinetic energy. The emission flux is calibrated using a silver-coated quartz crystal microbalance. The thin shape of the probe and transverse emission geometry of this emission device allow the emission area to be positioned close to the substrate surface, enhancing the irradiation flux at the substrate. AO irradiation is crucial for formation of TiO(2) phases via oxidation of the deposited TiN laser plume, and is effective for decrease of the substrate temperature for crystallization of anatase phase to as low as around 200 °C.     

Generation,growth, shrinkage,and dispersion of Au agglomerates in Si during the annealing of supersaturated substitutional Au

Si samples homogeneously pre-indiffused with Au atoms at a concentration 7.5 × 10¹⁶ atoms/cm³ were heat treated at 900 °C for 22.5, 90, 360, and 1,440 h to generate Au agglomerates during the out-diffusion process of supersaturated high-temperature substitutional Au. The number of Au atoms in all of the agglomerates in the regions 8–22, 22–36, 36–50, and 50–64 μm from the surface were measured by secondary ion mass spectrometry, and the change of their distributions during annealing was obtained. As a result, agglomerates containing (1–3) × 10⁵ Au atoms were initially generated with a concentration of 1.1 × 10¹⁰ agglomerates/cm³ at a short annealing time. The generated agglomerates grow, shrink, and disperse with the decrease of the supersaturation of the surrounding Au concentration, that is, with increase of annealing time. The boundary Au concentration for changing from growth to shrinkage of the agglomerates is (3–5) × 10¹⁵ atoms/cm³. The agglomerates grow and contain until about 2.3 × 10⁶ atoms. The agglomerates disperse and finally disappear as the surrounding Au concentration decreases to its thermal equilibrium value with continued annealing. It is difficult to explain the continuous generation, growth, shrinkage, and dispersion of the agglomerates during annealing using the usual theoretical treatment of agglomeration of supersaturated solutes in solids.