Blockade of metabotropic glutamate receptors prevents long-term memory consolidation

Metabotropic glutamate receptor activation has been shown to be essential for establishment of long-term potentiation, a phenomenon increasingly thought to be associated with the laying down of permanent memory. However, these receptors may also play a part in the initiation of protein kinase C activity, which has been demonstrated to be involved in prelong-term memory processes. Blockade of the metabotropic glutamate receptors by the specific antagonist, (RS)-α-Methyl-4-carboxyphenylgycine (500 μM) is shown to induce amnesia during a long-term memory stage in day-old chicks trained on a passive avoidance task, and to have no effect on prelong-term stages. The results suggest a specific role for these receptors in a possibly LTP associated mechanism of memory processing.     

Preparation of substained-release microspheres of phenylpropanolamine HCl and their release characteristics

Sustained release microspheres containing phenylpropanolamine HCl (PPA) were prepared with acrylic polymer (Eudragit RL/RS) sand hydroxypropylmethylcellulose phthalate (HPMCP) using a emulsion-solvent evaporation method. Magnesium stearate was used a smoothing agent for preparation of microspheres. The microspheres obtained were very spherical and free-flowing particles. Scanning electron microscopy showed that microspheres have a smooth surface and a sponge-like internal structure. The dissolution rate of PPA from the microspheres was dependent on the pH of dissolution media. PPA showed faster release in pH 1.2 solution than in pH 7.4 solution due to the solubility of PPA. Therefore we prepared new microspheres containing 5% (w/v) HPMCP in order to control the release of PPA. The release rate of PPA from these new microspheres was similar in pH 1.2 and pH 7.4 solution.     

Investigation of the cortico-reticulo-spinal connections in cats

Stimulation of the motor cortex evoked postsynaptic potentials in bulbar reticulo-spinal neurons of anaesthetized cats. In 72.4% of reticulo-spinal neurons they were identified as monosynaptic. According to the time characteristics they were classified into two groups (‘fast’ and ‘slow’). Corticobulbar fibres projecting to reticulospinal neurons could be also differentiated as ‘fast’ (conduction velocities above 20 m/s) and ‘slow’ (condition velocities below 20 m/s). Evidence was obtained that ‘fast’ cortico-fugal excitatory postsynaptic potentials are mediated by ‘fast’ cortico-bulbar fibres, and ‘slow’ excitatory postsynaptic potentials by the ‘slow’ ones. It was found that reticulo-spinal neurons with axon conduction velocities of 10.8–65 m/s can be activated by both ‘fast’ and ‘slow’ cortico-bulbar fibres, and the neurons with conduction velocities above 65 m/s only by the ‘slow’ ones. The background activity of reticulo-spinal neurons with slow conducting axons can be characterized as ‘tonic’ (with relatively uniform interspike interval distribution) while the activity of ‘fast’ neurons as ‘phasic’ (with significant grouping of discharges).The possible functional role of the differentiated cortico-reticulo-spinal connections is discussed.     

Preparation of prolonged release clarithromycin microparticles for oral use and theirin vitro evaluation

Prolonged release microparticles of clarithromycin (CL) were prepared using Eudragit RL 100 and RS 100 by spray-drying and casting-drying techniques. For the characterization of those microparticles, preparation yield, particle size distribution, X-ray diffraction, thermal behavior, active agent content and in vitro dissolution from the microparticles were performed. HPLC was used for the assay of clarithromycin and the assay method was validated. All the formulations obtained showed prolonged release when compared to pure clarithromycin. Microparticles prepared by spray-drying method had a slower release compared to those of casting-drying method. Spray-drying method seems to be a more suitable method to prepare microparticles for prolongation in release.     

Comparison of 5-HT4 receptors in guinea-pig colon and rat oesophagus: effects of novel agonists and antagonists

5-HT₄ receptors in isolated distal colon myenteric plexus of guinea-pig, mediating contraction of longitudinal smooth muscle, have been further characterized by selective agonists and antagonists. The indole agonists, 5-HT and 5-methoxytryptamine (5-MeOT), were full agonists (relative to 5-HT) with potency values (pEC₅₀) of 8.0 ± 0.1 (n = 50) and 7.8 ± 0.1 (n = 12), respectively. 5-HT₄ receptor agonists of other structural classes, including benzimidazolones (BIMU 1 and BIMU 8), and benzamides ((S)-zacopride, (R)-zacopride, renzapride, SC 49518) were partial agonists with intrinsic activities less than that of 5-HT. In general, the potencies for these compounds at 5-HT₄ receptors in guinea-pig colon were similar to the potencies seen in the rat isolated oesophagus, where 5-HT₄ receptors mediate relaxation.GR 113808 {[1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl1-methyl-1H-indole-3-carboxylat}, RS 39604 {1-[4-amino-5-chloro-2-(3,5-dimethoxybenzyloxy)phenyl]-3-[1-[2-[(methylsulfonyl)amino] ethyl]-4-piperidinyl]-1-propanone hydrochloride and SB 204070 {(1-n-butyl-4-piperidinyl)methyl 8-amino-7-chloro-1,4-benzodioxane-5-carboxylate} antagonized 5-HT responses with pA₂ values of 9.1 ± 0.1, 9.0 ± 0.2 and 11.0 ± 0.1, respectively. These affinity values were similar to those obtained at 5-HT₄ receptors in isolated rat oesophagus (9.0 ± 0.4, 9.3 ± 0.1 and 10.6 ± 0.1, respectively).Despite these operational similarities between 5-HT₄ receptors in guinea-pig colon and rat oesophagus, several novel compounds have revealed important differences between 5-HT₄ receptors in the two tissues. For example, the substituted benzoate, RS 23597 {3-(piperidine-1-yl) propyl-4-amino-5-chloro-2-methoxybenzoate hydrochloride, acted as a partial agonist (intrinsic activity 0.5) in guinea-pig colon with a potency of 7.6 ± 0.1 (n = 16). In isolated rat oesophagus, however, this compound was a surmountable antagonist (pA₂ = 7.8 ± 0.1) with no intrinsic activity. In contrast, the substituted naphthalimide (S)RS 56532 {(S)6-amino-5-chloro-2-(1-azabicyclo[2, 2, 2]octan-3-yl)2,3-dihydro-1H-benz isoquinoline-1,3-dione hydrochloride}, was a potent (pEC₅₀ = 7.9 ± 0.1), efficacious partial agonist (intrinsic activity = 0.8) in the rat oesophagus. However, in guinea-pig colon, it was a surmountable antagonist with an affinity (pK_B) of 9.4 ± 0.1. Furthermore, several novel, selective, 5-HT₄ compounds also showed opposing patterns of intrinsic activities similar to those described for RS 23597 and (S)RS 56532.It is concluded that these differences are inconsistent with differences in 5-HT₄ receptor reserves, and may suggest that 5-HT₄ receptors in the guinea-pig colon and the rat oesophagus can be operationally distinguished.     

3S技术在研究自然环境因素对疟疾传播影响中的应用

自然因素与疟疾传播的关系密切,国内外对气温、降雨量、湿度和地形地貌等自然因素与疟疾传播的关系作了大量研究。近年来以计算机和空间技术为基础发展起来的3S技术［地理信息系统（GIS）、遥感（RS）和全球定位系统（GPS）］在疟疾研究的资料收集、数据分析和模型建立等方面广泛应用,本文对3S技术在自然因素与疟疾传播关系中的应用和研究进展进行综述。     

Distribution, morphology, and synaptic targets of corticothalamic terminals in the cat lateral posterior-pulvinar complex that originate from the posteromedial lateral suprasylvian cortex

The lateral posterior (LP) nucleus is a higher order thalamic nucleus that is believed to play a key role in the transmission of visual information between cortical areas. Two types of cortical terminals have been identified in higher order nuclei, large (type II) and smaller (type I), which have been proposed to drive and modulate, respectively, the response properties of thalamic cells (Sherman and Guillery [1998] Proc. Natl. Acad. Sci. U. S. A. 95:7121-7126). The aim of this study was to assess and compare the relative contribution of driver and modulator inputs to the LP nucleus that originate from the posteromedial part of the lateral suprasylvian cortex (PMLS) and area 17. To achieve this goal, the anterograde tracers biotinylated dextran amine (BDA) or Phaseolus vulgaris leucoagglutinin (PHAL) were injected into area 17 or PMLS. Results indicate that area 17 injections preferentially labelled large terminals, whereas PMLS injections preferentially labelled small terminals. A detailed analysis of PMLS terminal morphology revealed at least four categories of terminals: small type I terminals (57%), medium-sized to large singletons (30%), large terminals in arrangements of intermediate complexity (8%), and large terminals that form arrangements resembling rosettes (5%). Ultrastructural analysis and postembedding immunocytochemical staining for gamma-aminobutyric acid (GABA) distinguished two types of labelled PMLS terminals: small profiles with round vesicles (RS profiles) that contacted mostly non-GABAergic dendrites outside of glomeruli and large profiles with round vesicles (RL profiles) that contacted non-GABAergic dendrites (55%) and GABAergic dendritic terminals (45%) in glomeruli. RL profiles likely include singleton, intermediate, and rosette terminals, although future studies are needed to establish definitively the relationship between light microscopic morphology and ultrastructural features. All terminals types appeared to be involved in reciprocal corticothalamocortical connections as a result of an intermingling of terminals labelled by anterograde transport and cells labelled by retrograde transport. In conclusion, our results indicate that the origin of the driver inputs reaching the LP nucleus is not restricted to the primary visual cortex and that extrastriate visual areas might also contribute to the basic organization of visual receptive fields of neurons in this higher order nucleus.     

Neurotoxic effects of colchicine: Differential susceptibility of CNS neuronal populations

Colchicine injected into the dentate gyrus of the hippocampus in adult rats preferentially destroys dentate granule cells. In the present study, we examine the light- and electron-microscopic correlates of the degeneration and evaluate whether the selectivity is preserved across the range of doses between 0.18 and 25 μg. Colchicine in a similar dose range was also injected into the cerebellum, olfactory bulb, striatum and cerebral cortex to examine local and regional differences in susceptibility to colchicine.The morphological changes accompanying degeneration in the dentate gyrus include fragmentation of the granule cell layer, appearance of small dark staining bodies in the cell layer, massive microglial invasion and profound disruption of granule cell axons and dendrites. Electron-microscopic observations suggest that the small dark bodies are probably condensed nuclei. The preferential vulnerability of dentate granule cells following intrahippocampal injection was observed at all doses. At doses between 0.18 and 2.5 μg there was little evidence of damage to neurons other than dentate granule cells. At the highest dose tested (25 μg) some pyramidal cells of regio superior near the injection site were destroyed, while granule cell destruction extended several mm from the injection site. Injection of 0.5–25 μg into the cerebellum resulted in the destruction of both granule cells and Purkinje cells, while cells which appeared to be neurons in the molecular layer were less affected. Following injection of 0.5 μg into the olfactory bulb, granule cells were extensively destroyed and there appeared to be some loss of mitral cells and an overall shrinkage of the injected bulb. Neuronal destruction in the striatum was observed with colchicine injections ranging from 2.5 to 25 μg, but at a given dose, the destruction was less extensive than for any other region tested except cerebral cortex.A possible application of this method and the implications of these results for other investigators using colchicine in the brain are discussed.