Transporter reversal as a mechanism of glutamate release from the ischemic rat cerebral cortex: studies with DL-threo-beta-benzyloxyaspartate

Elevated levels of the excitotoxic amino acids, glutamate and aspartate, have been implicated in the pathogenesis of neuronal injury and death induced by cerebral ischemia. This study evaluated the contribution of reversed high-affinity, Na(+)-dependent, glutamate transport to the ischemia-evoked release of glutamate and aspartate using DL-threo-beta-benzyloxyaspartate (DL-TBOA), a newly developed competitive, non-transported blocker of the EAAT 1-3 transporters. Changes in the extracellular levels of these and other amino acids, and of glucose and lactate in cerebral cortical superfusates during four-vessel occlusion-elicited global cerebral ischemia were examined using a cortical window technique. Basal and ischemia-evoked amino acid, glucose and lactate efflux were compared in control versus DL-TBOA (100 microM; applied topically for 35 min prior to ischemia) animals. Twenty minutes of ischemia caused large increases in aspartate, glutamate, GABA and taurine effluxes into cortical superfusates, with non-significant effects on the efflux of glycine, glutamine, alanine and serine. Application of DL-TBOA caused a 2-fold increase in basal, preischemic, extracellular glutamate levels, but did not affect those of the other compounds. In the presence of DL-TBOA, ischemia-evoked release of aspartate, glutamate, taurine and glutamine was significantly reduced; that of the other amino acids was not affected. The ischemia-evoked declines in glucose were significantly attenuated, and lactate release was enhanced above that in control animals. The amino acid data are interpreted as indicating that aspartate and glutamate releases were reduced as a consequence of DL-TBOA inhibition of reversed transport by high-affinity, Na-dependent carriers, predominantly involving the glial EAAT 2 transporter. The reduction in ischemia-evoked taurine release is interpreted as being due to a decrease in cell swelling prior to and during the initial phase of ischemia due to reduced entry of the Na(+), and other ions, associated with a decreased glutamate uptake. Glucose-sparing and availability for lactate formation would also result from a reduced glutamate/Na(+) uptake. These results indicate that reversed transport, primarily from glial cells by the EAAT 2 carrier, is responsible for a substantial (42 and 56%) portion of the ischemia-evoked increase in extracellular glutamate and aspartate levels, respectively. As a potent, competitive, non-transported blocker of high-affinity, Na(+)-dependent, glutamate transporters, DL-TBOA promises to be a valuable new compound for the study of glutamatergic mechanisms.     

加入WTO后我国健康相关产品管理的挑战与机遇

2001年我国加入世界贸易组织(WTO)，作为WTO成员国按照国际贸易规则建立一个完整的、更具活力和长久性的多边产品贸易体制，促进和规范产品贸易良好发展是我们面临的任务之一。WTO成员国通过降低关税和其他贸易壁垒，在国际贸易中消除歧视性待遇，达到互惠互利的目的。WTO诸     

儿童散光度散光轴向的分析

目的:探讨3～10岁儿童散光度散光轴向分布情况。方法:10g/L阿托品常规散瞳验光检查2299眼。结果:3～10岁儿童散光度分布在0.25～2.00D,合例散光占96.35%,反例散光占0.52%,斜轴散光占3.13%。结论:3～10岁儿童散光以合例散光为主,斜轴散光次之,极少部分为反例散光。     

WHO 网站与药物流行病学

目的：介绍世界卫生组织网站中的药物流行病学信息。方法：介绍世界卫生组织网站结构和药物流行病学信息所处栏目。结果：药物流行病学信息主要分布于健康主题和WHO子网站中。结论：世界卫生组织网站中有丰富的药物流行病学信息。     

老年食管癌围手术期的处理要点与体会

目的:提高老年人食管癌手术治疗成功率及降低其围术期死亡率。方法:对30例老年食管癌实行开胸手术患者的围手术期准备、术前检查、处理、手术方法及术后并发症的防治等进行分析。结果:本组手术切除率为100%,无死亡病例,无吻合口瘘。出现呼吸衰竭、窒息各1例。结论:选择好手术适应症,充分准备围手术期各项指标及术后预防呼吸、循环衰竭是手术成功的关键。     

降低体重指数对原发性高血压病降压效果的影响及其临床意义

目的探讨降低体重指数(BodyMassIndex,BMI)对原发性高血压病降压效果的影响及其临床意义。方法选择40例超重或肥胖的(BMI≥24)原发性高血压病患者,分为治疗组与对照组,降低治疗组患者的体重指数,同时观察两组治疗前后血压的变化。结果发现治疗组患者降低体重指数后血压有明显下降,与对照组相比有显著的临床意义(P<0.05)。结论降低超重或肥胖的高血压病患者的体重指数可起到一定的降压效果,应注意降低患者的体重指数。     

Vitapex糊剂在儿童年轻恒牙根尖诱导成形术中的应用

目的探讨Vitapex糊剂和氢氧化钙糊剂用于儿童年轻恒牙根尖诱导成形术的治疗效果。方法对85例儿童,98颗牙根尖发育未完成,牙髓病变已波及根髓、牙髓已坏死或并发根尖周炎的年轻恒牙分为2组,分别用Vitapex糊剂和氢氧化钙糊剂进行根尖诱导成形术,观察其根尖发育情况。结果Vitapex糊剂组总有效率为91.84%。氢氧化钙组总有效率为77.55%。2者疗效在统计学比较存在显著性。结论Vitapex糊剂作为一种根尖诱导成形剂具有良好的治疗效果。值得在临床推广应用。     

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

The nucleocapsid （N） protein of SARS-coronavirus （SARS-CoV） is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DHSalpha and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobutins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity （DTH） and CD^8＋ CTL responses to N protein.     

Pericyte and microvascular diseases

Pericytes are perivascular cells of microcirculation, which construct the barrier between the microcircula-tion and interstitial fluid with endothelial cell and basement membrane. Contractility and other multifunctional activities of pericytes are now being elucidated. Pericytes are pluripotential cells (i. e. as a source of other cell types)and take part in many biological and pathological procedures, such as vascularization, vascular remodeling , microvessel permeability and wound healing, etc. The functional interaction of pericytes with endothelial cells (EC) is now being established. The disfunction and population alteration of pericytes are characterized in many microvascular diseases, such as diabetic retinopa-thy, vascularization of tumors, hypertension,etc.     

不孕不育者对人工授精技术的伦理态度调查研究

目的：研究不孕不育者对人工授精技术的伦理态度,促进该项技术更好地为患者服务.方法：自制问卷调查了223名不孕不育者.结果：不孕不育者对AIH、AID的态度存在显著差异（P＜0.05）;对婚姻家庭生活选择相对宽容;精子的商品化趋向值得关注;必须采取一定措施以保证精子和人工授精儿的质量.结论：AID会引发许多伦理问题,临床应用时更应遵循有利于患者、知情同意等伦理原则和相关法律规定,以减少纠纷,造福社会.