Developmental change of the inhibition by lead of NMDA-activated currents in cultured hippocampal neurons

The inhibition of N-methyl-D-aspartate (NMDA)-activated current in cultured fetal rat hippocampal neurons by Pb2+ was investigated at various stages of cell development. Pb2+ selectively inhibited NMDA currents recorded from young cultured neurons. In the first week of culture, Pb2+ showed the most prominent inhibition, which was gradually attenuated in the following weeks. Pb2+'s action was selective for NMDA- as opposed to either kainate- or quisqualate-induced currents. The current-voltage relationship for NMDA-induced currents in the presence of Pb2+ revealed that the effect of this cation was voltage-independent, which suggested that the site of interaction of Pb2+ with the NMDA receptor/channel is located outside the membrane electric field. Single channel studies showed that Pb2+ reduced the frequency but not the lifetime of the NMDA-activated single channel currents. Further evaluation of the mechanism of action of Pb2+ on the NMDA receptor demonstrated that this cation is a noncompetitive antagonist of both NMDA and glycine. We have demonstrated that the NMDA-induced whole cell currents change along with cell development, and the effects of Pb2+ are also dependent upon age of culture. The NMDA-induced currents in cultured rat hippocampal neurons had two components, one that decayed rapidly and another that decayed slowly. The fast component was clearly observed at concentrations of glycine higher than 1 microM, whereas the slow component reached its maximum amplitude at the glycine concentration of 1 microM. Moreover, the rapidly decaying component of NMDA-evoked whole cell currents was predominant in young cultured neurons, and its contribution to the total current was reduced in old cultured neurons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Allosteric modulation of Torpedo nicotinic acetylcholine receptor ion channel activity by noncompetitive agonists

Similar to other neuroreceptors of the vertebrate central nervous system, the nicotinic acetylcholine receptor (nAChR) is subject to modulatory control by allosterically acting ligands. Of particular interest in this regard are allosteric ligands that enhance the sensitivity of the receptor to its natural agonist acetylcholine (ACh), as such ligands could be useful as drugs in diseases associated with impaired nicotinic neurotransmission. Here we discuss the action of a novel class of nAChR ligands which act as allosterically potentiating ligands (APL) on the nicotinic responses induced by ACh and competitive agonists. In addition, APLs also act as noncompetitive agonists of very low efficacy, and as direct blockers of ACh-activated channels. These actions are observed with nAChRs from brain, muscle and electric tissue, and they depend on the structure of the APL and the concentration range applied. We focus here on Torpedo nAChR because (i) the unusual pharmacology of these ligands was first discovered with this system, and (ii) large quantities of this receptor are readily available for biochemical studies.     

Contribution of nicotinic receptors to the function of synapses in the central nervous system: the action of choline as a selective agonist of alpha 7 receptors

The alpha 7-nicotinic receptor (nAChR)-selective agonist choline and nAChR-subtype-selective antagonists led to the discovery that activation of both alpha 7 and alpha 4 beta 2 nAChRs located in CA1 interneurons in slices taken from the rat hippocampus facilitates the tetrodotoxin (TTX)-sensitive release of gamma-aminobutyric acid (GABA). Experiments carried out in cultured hippocampal neurons not only confirmed that preterminal alpha 7 and alpha 4 beta 2 nAChRs modulate the TTX-sensitive release of GABA, but also demonstrated that evoked release of GABA is reduced by rapid exposure of the neurons to acetylcholine (ACh, 10 microM-1 mM) in the presence of the muscarinic receptor antagonist atropine (1 microM). This effect of ACh, which is fully reversible and concentration-dependent, is partially blocked by superfusion of the cultured neurons with external solution containing either the alpha 7-nAChR-selective antagonist methyllycaconitine (MLA, 1 nM) or the alpha 4 beta 2-nAChR-selective antagonist dihydro-beta-erythroidine (DH beta E, 100 nM). A complete blockade of ACh-induced reduction of evoked release of GABA was achieved only when the neurons were perfused with external solution containing both MLA and DH beta E, suggesting that activation of both alpha 7 and alpha 4 beta 2 nAChRs modulates the evoked release of GABA from hippocampal neurons. Such mechanisms may account for the apparent involvement of nAChRs in the psychological effects of tobacco smoking, in brain disorders (e.g., schizophrenia and epilepsy), and in physiological processes, including cognition and nociception.     

New finding of Phlebotom uses in the State of S?o Paulo with special reference to Lutzomyia longipalpis]

The removal by centrifugation of epididymal contents from mouse spermatozoa had no deleterious effect on fertilization in vitro, and, depending on the genotype of the gametes, was frequently associated with increased levels of fertility. Washing of the spermatozoa significantly improved the fertilization rate of F1 eggs with TO spermatozoa and of BALB/c eggs with BALB/c spermatozoa, but had no significant effect of F1 spermatozoa with F1 eggs.     

Effect of sex and age on bone mass, body composition and fuel metabolism in humans

The mechanism(s) governing the gain of upper-body fat and its relationship to the decrease in bone mass with age is still unclear. Therefore, four groups of subjects matched for weight, height, and body mass index (n = 119; 60 women, 59 men), but differing in age (above and below 50 y) and sex were investigated using dual energy x-ray absorptiometry (DXA) to assess body composition (bone, lean, and fat mass as well as its distribution) and indirect calorimetry to determine resting fuel metabolism. Fat mass of trunk and arms (P < 0.01), but not legs, increased with advancing age in males, resulting in a continuous increase in the ratio of upper- to lower-body fat (r = 0.45, P < 0.001). In contrast, total fat mass remained stable in women, irrespective of menopause, but a redistribution of fat occurred with advancing age (r = 0.43, P < 0.001), resulting in a higher upper- to lower-body fat ratio (P < 0.05) in older than in younger women. Total lean soft-tissue mass of all segments of the body was greater in men than in women irrespective of age (P < 0.001), and lower in the older groups than in the younger ones irrespective of sex. In males, but not females, lean soft-tissue mass in arms and legs decreased (r = 0.57, P < 0.001), whereas the ratio of total fat to lean soft-tissue mass increased (r = 0.53, P < 0.001) with age. Bone mineral content correlated with total body fat in both groups of women and in young males (r > 0.5, P < 0.001), but not in older males. With advancing age, the proportion of lean soft-tissue mass occupied by total skeleton declined in women (n = 59, P < 0.001), but remained stable in males. Resting energy expenditure decreased with age in both sexes. Protein and carbohydrate oxidation were similar in all four groups of subjects. Total fat oxidation and fat oxidation per kilogram of lean soft-tissue mass decreased with age (r > 0.36, P < 0.01) in males, but not in females, whereas it increased with increasing fat mass in females (r > 0.32, P < 0.03), but not in males. In contrast, fat oxidation per kilogram of fat mass decreased with fat mass in males (r = 0.61, P < 0.001), but not in females. Our results suggest that aging affects body composition and fuel metabolism differently in each gender, leading to reduced fat oxidation and accumulation of upper-body fat with loss of striated muscle in men, and to an increased ratio of upper- to lower-body fat and bone loss in women, the latter depending on fat mass.     

Myelodysplastic syndromes (MDS): prognostic factors and scoring systems

OBJECTIVE: To evaluate the score systems of Cassano and Sanz and suggest a new one. DESIGN: Case series. LOCATION: Teaching hospitals: EPM UNIFESP and Faculdade de Medicina de Botucatu. PARTICIPANTS: 59 patients diagnosed from 1979 to 1992. INTERVENTION: Evaluation of clinical-laboratorial data. MEASUREMENT: Statistical comparison, uni and multivariate analysis and actuarial survival curves. RESULTS: Cassano's system divided the patients into high and low risk (p = 0.0966) while Sanz's gave high, intermediate and low risk (p = 0.0108). The univariate analysis showed hemoglobin, WBC count, E/M ratio, liver size and blast percentage in BM as statistically significant. The multivariate analysis showed blast percentage in BM (p = 0.004) and Hb (p = 0.050) as significant. Our system, considering the multivariate analysis data, divided the patients into high, intermediate and low risk (p = 0.0038). CONCLUSIONS: Sanz's system was more functional than Cassano's, while ours showed predictive survival value and ease of use in clinical practice.     

产品品牌与服务品牌的双亮相——汇利堡携代理品牌打造汽车改装王国

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