伴行为和精神症状痴呆患者的脑葡萄糖代谢研究

目的:研究有、无痴呆的行为和精神症状(BPSD)的阿尔茨海默病(AD)患者脑葡萄糖代谢的不同特点,以探讨AD患者BPSD的病理生理及其与大脑神经病理之间的关系。方法:对13例符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的AD患者,其中6例有BPSD(BPSD组),7例无BPSD(NBPSD组),并进行PET检查,对各脑区局部脑葡萄糖代谢率(rCMRglc)及多个核团进行测定,并用统计参数图(SPM)对两组脑PET图像进行像素间比较。结果:①BPSD组的AD患者额叶放射性减低者多于NBPSD组(4/6∶2/7);②应用感兴趣区(ROI)方法进行比较,BPSD组和NBPSD组在所选脑区中的rCMRglc差异无显著性(P>0.05);③应用SPM方法进行比较发现,BPSD组和NBPSD组rCMRglc显著减低的脑区主要分布在前额叶、顶枕交界处和颞下回。BPSD组比NBPSD组rCMRglc减低面积大,左侧额叶上回、右侧颞叶前内部、右侧岛叶前下部葡萄糖代谢减低。结论:AD患者,不管有无BPSD,rCMRglc减低区主要位于前额叶、顶枕叶交界处和颞叶下回;有BPSD的AD患者比无BPSD的患者rCMRglc的减低区面积大,分布广,程度重,提示BPSD可能是AD病程中的一个症状,而并非是另一种AD类型;额叶rCMRglc减低可能与BPSD的发生有关。     

中学生苯二氮(艹卓)类药使用调查

目的:了解武汉地区中学生使用苯二氮艹卓(BZD)类药的现状。方法:采用整群抽样方式,在武汉市7个中心城区,共抽取258个班,采用自行设计的问卷,共获有效问卷12345份。调查数据采用SPSS10.0软件进行统计。结果:调查发现武汉市中学生BZD的使用率为4.0%,依赖的发生率为4.1‰,男生多于女生(P<0.01)。服药和未服药的学生在对药物认识上差异有显著性(P<0.01)。为摆脱烦恼(14.1%),好奇(13.3%),受周围人影响(10.8%),寻求快乐(9.9%)等动机,是BZD滥用的主要原因。多元Logistic回归分析发现:不遵医嘱、性别、经常喝酒、认为好玩和有益无害、经常抽烟、与父母关系、母教育方式、父文化、父母间关系、年级等是BZD使用的危险因素。结论:武汉地区确实存在中学生滥用BZD的现象,而使用的原因是个人、家庭、社会多因素的结果。     

甜菜碱对HepG2人肝癌细胞[Ca2+]i和细胞膜电位的影响

目的研究甜菜碱对肝癌HepG2细胞内游离Ca2 浓度([Ca2 ]i)和细胞膜电位的影响。方法Fluo-3/AM标记,激光扫描共聚焦显微镜观察HepG2细胞[Ca2 ]i,TMRE标记,激光扫描共聚焦显微镜测定细胞膜电位的影响。结果甜菜碱能够升高HepG2细胞[Ca2 ]i,降低细胞膜电位。升高[Ca2 ]i的强度具一定的剂量依赖性,随甜菜碱剂量的增大而升高。甜菜碱50、25mg/mL组与对照组比较差异非常显著(P<0.01),甜菜碱12.5mg/mL组与对照组比较差异显著(P<0.05)。给药48h时间段内细胞内的[Ca2 ]i升高的幅度较大,72h升高幅度相对较小。而降低膜电位上,在48h时间段内,甜菜碱50、25、12.5mg/mL各组膜电位均显著高于对照组(P<0.05),但在72h时间段内甜菜碱12.5mg/mL组与对照组比较没有显著性差异(P>0.05)。结论甜菜碱通过开放细胞膜上的通透性转换孔道(MPTP),从而升高HepG2细胞[Ca2 ]i,启动细胞凋亡机制,诱导HepG2细胞凋亡。     

Binding of [3H]MK-801 in subcellular fractions of Schistosoma mansoni: evidence for interaction with nicotinic receptors

Several studies have suggested that l-glutamate is a putative neurotransmitter in Schistosoma mansoni. Recently, we detected the presence of low-affinity binding sites for [(3)H]kainic acid in the heterogeneous (P(1)) subcellular fraction of S. mansoni. In an attempt to characterize N-methyl-d-aspartate (NMDA) receptors in this worm, we performed binding assays with [(3)H]MK-801, a NMDA non-competitive antagonist, in the P(1) fraction of adult S. mansoni. In competition experiments, MK-801 (IC(50) approximately 200 microM) and ketamine (IC(50) approximately 500 microM) exhibited a low affinity for the sites labeled with [(3)H]MK-801. Along with the lack of modulation of this binding by glutamatergic agonists and antagonists and the absence of stereoselectivity for MK-801 isomers, these results suggest that [(3)H]MK-801 could label a site different from the classical NMDA receptor in S. mansoni. Based on the evidences that MK-801 interacts with mammalian muscle and central nervous system nicotinic receptors as a low-affinity noncompetitive antagonist, we have investigated the effects of MK-801 on the nicotine-induced flaccid paralysis of the worm, in vivo. The motility of S. mansoni was quantified by image analysis through a measure of displacement of the worm's extremities. In the presence of (-)-nicotine (10-100 microM), we observed an immediate paralysis of the worms, that was inhibited by 1mM MK-801. Besides nicotine, choline (10-50mM) was also able to inhibit the worm's motility. As a conclusion, we suggest that [(3)H]MK-801 binds to nicotinic receptors, and not NMDA receptors, in subcellular fractions of S. mansoni.     

Dansylarginine N-(3-ethyl-1,5-pentanediyl)amide: A potent and selective fluorescent inhibitor of butyrylcholinesterase

Interactions between dansylarginine N-(3-ethyl-1,5-pentanediyl)amide (DAPA) and the cholinesterases were examined by the techniques of enzyme kinetics and fluorescence spectroscopy. When tested with partially purified enzyme preparations, DAPA was a potent inhibitor of butyrylcholinesterase $\text{(}\text{IC}{}_{50}\text{= 2 × 10}{}^{\mathrm{?7}}\text{M}\text{)}$ but not of acetylcholinesterase $\text{(}\text{IC}{}_{50}\text{= 4 × 10}{}^{\mathrm{?4}}\text{M}\text{)}$. For a detailed study of the effects of DAPA on butyrylcholinesterase (BuChE), the enzyme was purified to homogeneity from horse serum, with the aid of affinity chromatography on N-methyl acridinium. The kinetics of the inhibition of purified BuChE by DAPA were complex, having both competitive and non-competitive features, and it was not possible to estimate K_i unambiguously. Spectroscopic measurements showed that the fluorescence of the dansyl moiety was strongly affected by the binding to BuChE. With excitation at 330 nm, total fluorescence emission from bound DAPA (at 450 nm and above) was 21-fold greater than from free DAPA. In a titration experiment, this enhancement of fluorescence intensity was used to calculate that each monomer of BuChE has two apparently independent DAPA-binding sites with a K_d of 4.5 × 10^?7 M. Further measurements showed that the fluorescence emission of bound DAPA was markedly blue-shifted (to 502 nm from 570 nm in free solution) and that the fluorescence lifetime of this form was greatly prolonged (to 24 nsec from 2.7 nsec). These observations indicate that the high affinity binding sites on BuChE lock DAPA in a highly non-polar environment.     

Temperature sensitivity of axonal transport in hibernating and nonhibernating rodents.

The temperature sensitivity of fast axonal transport of labeled protein in peripheral sensory axons was investigated in rats and hibernating and non-hibernating ground squirrels (Spermophilus r. richardsonii), using an in vitro technique which permitted incubation of the sciatic nerve for various periods of time at different temperatures. The relationship between velocity and temperature was exponential between 13 and 38°C, but below 13°C transport ceased or became too slow to detect. There were no significant differences in the relationship between temperature and velocity for the three classes of nerve studied. It is concluded that the peripheral nerves of hibernating ground squirrels are not modified to permit axonal transport to continue at the low body temperatures characteristic of the hibernating state.     

Renal transport of 2'-deoxytubercidin in mice

Previous results [J. F. Kuttesch, Jr. and J. A. Nelson, Cancer Chemother, Pharmac. 8, 221 (1982)] from this laboratory indicate that mechanisms exist for renal secretion of 2'-deoxyadenosine and possibly for reabsorption of adenosine in humans and in mice. Since significant metabolism of these purine nucleosides occurs even in the presence of adenosine deaminase inhibitors, the renal handling of a compound which is not significantly metabolized by the deaminase or by kinases was studied. Unlike 2'-deoxyadenosine itself, the 2'-deoxyadenosine analog, [4-amino-7-(2'-deoxy-beta-D-erythro-pentofuranosyl)-pyrrolo-(2,3-d)pyrimidine; 2'-deoxytubercidin], is not significantly metabolized by mammalian tissues. In mice, the renal plasma clearance of 2'-deoxytubercidin exceeded that of inulin by about 3-fold. Also, mouse kidney slices concentratively accumulated 2'-deoxytubercidin by a saturable and metabolically dependent process. The uptake by mouse kidney slices was inhibited by classical substrates for the organic cation secretory system (tetraethylammonium, choline and N1-methylnicotinamide) but was not markedly inhibited by classical substrates for the organic anion secretory system (p-aminohippurate, phenol red and probenecid). Since 2'-deoxytubercidin inhibited the active, concentrative uptake of [14C]tetraethylammonium, but failed to inhibit the uptake of p-[14C]aminohippurate by mouse kidney slices, it is concluded that 2'-deoxytubercidin may be secreted by the organic cation system. Additional studies are required, however, to unequivocally establish the relationships between 2'-deoxytubercidin, 2'-deoxyadenosine and tetraethylammonium renal secretory mechanisms.     

Ethacrynic acid influx and efflux in kidney cortex slices: Dependence on sodium gradient

Ethacrynic acid (EA) accumulation in rat kidney cortex slices was inhibited by reduction of sodium concentration in the incubation medium. Preloading of slices with sodium reduced EA accumulation at medium sodium concentration of 30–140 mM. Ouabain (10^?3 M) inhibited EA accumulation in kidney cortex slices of rabbit, guinea-pig, Psammomys obesus, rat, mouse and Acomys cahirinus in decreasing order. Ouabain inhibited the sodium pump in kidney cortex slices of these species in the same order. Ethacrynic acid efflux was faster from slices of rat kidney medulla than from kidney cortex. the efflux rate from cortical slices increased when sodium concentration in the incubation medium was lowered. Probenecid (10^?3 M) in the medium enhanced the efflux rate of EA from kidney cortex slices. It was concluded that EA fluxes in kidney cortex slices fit the model of a sodiumactivated carrier mechanism and that the sodium gradient across the cell membrane determines the direction of net EA transport.     

电离辐射对大鼠脑皮质牛磺酸、谷氨酸及其谷氨酸阳性神经元的影响

目的 探讨电离辐射对大鼠脑皮质内谷氨酸(glutamate,Glu)、牛磺酸(taurine,Tau)水平和谷氨酸阳性神经元的影响。方法 雄性SD大鼠45只随机分为3组,头部分别给予0、10、20 Gy ⁶⁰Coγ射线照射。照射后12h测定脑皮质谷氨酸(Glu)、牛磺酸的含量以及神经细胞内游离Ca²⁺浓度([Ca²⁺]i),同时观察大鼠脑皮质Glu阳性神经元以及神经细胞凋亡情况。结果 随着照射剂量的增加,脑皮质内Glu含量升高,Tau含量减少,Glu/Tau比值逐渐上升,细胞内游离Ca²⁺浓度([Ca²⁺]i)升高,Glu阳性神经元数量增加,细胞凋亡数量上升,并与电离辐射呈一定的量效关系。结论 上述结果提示Glu产生的神经毒作用参与了电离辐射对中枢神经系统的损伤过程。