硫化氢对老龄急性脑梗死大鼠海马CA3区突触结构的影响

目的评价硫化氢(H2S)对老龄急性脑梗死大鼠海马CA3区突触结构的影响。方法健康雄性SD大鼠60只,18~20月龄,体重500~700 g,采用随机数字表法分为4组,每组15只:对照组(C组)、模型组(M组)、Na HS组(N组)、生理盐水组(S组)。N组于制作模型前25 min给予大鼠腹腔注射H2S外源性供体Na HS(28μmol/kg);S组于制作模型前25 min给予大鼠腹腔注射等量生理盐水;C组不行任何处理。采用线栓法致大鼠大脑中动脉阻塞致急性脑梗死模型。于急性脑梗死后第1~5天每组随机取5只大鼠,进行Morris水迷宫进行测试,记录逃避潜伏期和穿越平台次数;于急性脑梗死后1、3、5 d(T1~T3)每组随机取5只大鼠处死,取海马组织,电镜下定量测定海马CA3区突触结构各项指标。结果与C组比较,M组、N组和S组大鼠急性脑梗死后逃避潜伏期延长,穿越平台次数减少,海马CA3区突触数减少,间隙增宽,突触后膜致密物厚度变薄,突触活性区长度缩短,突触界面曲率减小(P<0.05);与M组比较,N组急性脑梗死后逃避潜伏期缩短,穿越平台次数增多,海马CA3区突触数增加,间隙变窄,突触后膜致密物厚度变厚,突触活性区长度延长,突触界面曲率增大(P<0.05);与N组比较,S组急性脑梗死后逃避潜伏期延长,穿越平台次数减少,海马CA3区突触数减少,间隙增宽,突触后膜致密物厚度变薄,突触活性区长度缩短,突触界面曲率减小(P<0.05)。结论 H2S可改善老龄急性脑梗死大鼠认知功能,其机制可能与海马组织CA3区突触结构改变有关。     

丙泊酚对老龄大鼠认知功能及血清S100β蛋白神经特异性烯醇化酶的影响

目的探讨丙泊酚对老年大鼠认知功能及S100β蛋白、神经特异性烯醇化酶的影响。方法选用50只健康雄性Wistar大鼠,20月龄,体质量560~610 g,采用随机数字表法分为对照组(C组)25只和丙泊酚组(P组)25只。丙泊酚组腹腔注射60 mg/kg(6 ml/kg)丙泊酚,然后酌情追加,维持麻醉3 h。对照组腹腔注射等量0.9%氯化钠注射液(6 ml/kg)。于停药后1天开始行跳台实验(第1和7天)和Morris水迷宫实验(连续7 d)测试认知功能。于麻醉结束后的第1天和第7天测定血浆样本中S100β和神经特异性烯醇化酶(NSE)的浓度。结果与C组比较,P组丙泊酚麻醉结束后1 d时老龄大鼠跳台实验学习和记忆阶段潜伏期、受电击总时间均明显延长,错误次数增多(P<0.01)。麻醉结束后7 d时,2组间各指标差异无统计学意义(P>0.05)。丙泊酚麻醉结束后第1天老龄大鼠Morris水迷宫实验逃避潜伏期和总游泳距离明显延长(P<0.01),而2组大鼠在第7天水迷宫空间探索实验中原平台象限探索时间、探索距离、穿越平台次数间差异无统计学意义(P>0.05)。2组大鼠在丙泊酚麻醉后第1天和第7天血清S100β和NSE浓度差异无统计学意义(P>0.05)。结论丙泊酚麻醉后第1天老龄大鼠的被动回避能力和空间学习记忆能力可能会下降,但不会造成长时间(第7天)的影响;血清S-100β蛋白和NSE浓度在预测丙泊酚麻醉是否影响认知功能的价值不大。     

七氟醚对老龄大鼠海马CA3区突触结构的影响

目的观察七氟醚对老龄大鼠海马CA3区突触结构的影响。方法健康SD大鼠60只,18月龄,随机分为4组:空白对照组(C组)、3%七氟醚组(S1组)、1.5%七氟醚组(S2组)、3%异氟醚组(I组),每组15只。于麻醉结束后1、3、7 d(T1~T3)行Morris水迷宫实验,并测定海马CA3区突触结构各指标。结果与C组比较,I组T1~T3、S1组T1~T2时逃避潜伏期延长,穿越原平台象限次数减少,I组、S1组T1~T3海马CA3区突触间隙增宽,PSD厚度变薄,突触活性区长度缩短,突触界面曲率减小(P<0.05);与I组、S1组比较,S2组T1~T2时逃避潜伏期缩短,T1~T3海马CA3区突触间隙变窄,PSD厚度增厚,突触活性区长度延长,突触界面曲率增大(P<0.05);与I组比较,S1组、S2组T3时逃避潜伏期缩短,穿越原平台象限次数增加(P<0.05);与S1组比较,I组T3时逃避潜伏期延长,穿越原平台象限次数减少(P<0.05);与T1比较,I组、S1组、S2组T2~T3时逃避潜伏期缩短(P<0.05)。结论低浓度七氟醚对老龄大鼠认知功能无明显影响,高浓度七氟醚、异氟醚均可导致老龄大鼠认知功能减退,其机制可能与抑制海马CA3区突触结构的改变有关。     

鼠神经生长因子对急性脑梗死血清神经元烯醇化酶和S100β蛋白的影响

目的探讨鼠神经生长因子对急性脑梗死血清神经元烯醇化酶(NSE)和S100β蛋白的影响。方法 128例急性脑梗死患者随机分为两组,观察组64例,对照组64例,对照组采用常规治疗,观察组在常规治疗的基础上加用鼠神经生长因子。治疗前后测定血清NSE和S100β蛋白。结果两组治疗前ESS和ADL评分无明显差异(P>0.05);两组治疗后ESS和ADL评分均有明显升高(P<0.05),并且与对照组治疗后比较,观察组治疗后升高更明显(P<0.05)。两组治疗前患者血清NSE和S100β蛋白无明显差异(P>0.05);两组治疗后患者血清NSE和S100β蛋白均明显降低(P<0.05,P<0.01),并且与对照组治疗后比较,观察组治疗后降低更明显(P<0.05)。结论鼠神经生长因子可以明显降低急性脑梗死血清NSE和S100β蛋白的表达。     

神经元特异性烯醇化酶、S-100β蛋白与急性脑梗死关系的临床研究

目的探讨急性脑梗死患者血清神经元特异性烯醇化酶（NSE）和S-100β蛋白的变化及与急性脑梗死的关系。方法采用酶联免疫吸附法测定80例急性脑梗死患者NSE、S-B100β蛋白及40例健康体检者（对照组）血清NSE和S-100β蛋白含量。结果急性脑梗死患者血清NSE和S-100β蛋白浓度均明显高于对照组,差异有统计学意义（P〈0.05）,且NSE和S-100β蛋白水平随梗死面积的增大及神经功能缺损程度的加重逐渐升高,差异有统计学意义（P〈0.05）。结论血清NSE和S-100β蛋白水平较好地反映了急性脑梗死梗死面积及神经功能缺损程度,可以作为判断急性脑梗死梗死面积、评价疗效和估计预后的一个重要手段。     

瑞舒伐他汀对急性脑梗死患者血清S100β、NSE、sICAM-1、MMP-2、hs-CRP的影响

目的探讨瑞舒伐他汀对急性脑梗死患者血清S100β、NSE、s ICAM-1、MMP-2、hs-CRP的影响。方法选取我院2010年9月至2014年9月收治的急性脑梗死患者90例,随机分为观察组和对照组,每组45例,两组均给予阿司匹林、舒血宁等常规治疗,另外,观察组和对照组同时给予瑞舒伐他汀20 mg、10 mg口服,比较两组患者治疗前后的NIHSS评分,同时比较两组治疗前及治疗后14 d两组患者血清S100β、NSE、s ICAM-1、MMP-2、hs-CRP水平。结果治疗前,两组NIHSS评分及血清S100β、NSE、s ICAM-1、M M P-2、hs-CRP水平比较差异无统计学意义。治疗后,观察组NIHSS评分低于对照组(P<0.05),血清S100β[(0.08±0.05)μg/L]、NSE[(7.34±1.33)μg/L]、s ICAM-1[(104.68±10.51)μg/L]、M M P-2[(466.36±79.00)μg/L]、hs-CRP[(5.43±0.56)μg/L]低于对照组[(0.11±0.06)、(8.46±1.80)、(131.91±11.44)、(519.46±81.01)、(7.30±0.80)μg/L],两组比较差异有统计学意义(P<0.05或P<0.01)。结论瑞舒伐他汀可显著改善急性脑梗死患者的临床症状,降低血清S100β、NSE、s ICAM-1、MMP-2、hs-CRP水平,值得在临床治疗上予以推广。     

衣达拉奉对急性脑梗死患者血清NSE、S-100β的影响

目的探讨依达拉奉治疗急性脑梗死的疗效,以及其对血清神经元特异性烯醇化酶（NSE）、S-100β的影响。方法68例急性脑梗死患者随机分为观察组（常规治疗＋依达拉奉）和对照组（常规治疗）各34例,观察并比较两组的疗效,以及两组治疗前后血清NSE、S-100β的变化。结果治疗14d后,观察组的总有效率明显高于对照组（X^2=7．852,P〈0．05）。血清NSE和S-100β水平均较治疗前明显下降（P〈0．05、P〈0．01）,且观察组较对照组降低更明显（P〈0．05）。结论依达拉奉治疗急性脑梗死疗效确切,且能明显降低患者血清NSE、S-10015的水平,值得广泛推广和应用。     

急性脑卒中患者血浆ET、S-100B蛋白和NSE含量与神经功能缺损的临床研究

目的 探讨急性脑卒中患者（包括急性脑梗死、脑出血）血清神经元特异性烯醇化酶（NSE）、内皮素（ET）和S-100B蛋白浓度,观察其在急性期变化与神经功能缺损的关系。方法回顾性分析发病在24h内的急性脑卒中患者100例（其中脑梗死组45例,脑出血组55例）及对照组31例血清NSE、ET和S-100B蛋白水平变化,脑梗死、脑出血血清NSE、ET和S-100B蛋白水平与神经功能缺损程度的相关性。结果脑梗死组和脑出血组血清NSE、ET和S-100B蛋白水平均较对照组有不同程度增高（P〈0．01）。脑梗死组和脑出血组神经功能缺损的轻、中、重型3组血清NSE、ET和S-100B蛋白水平组间比较差异有统计学意义（P〈0．01）。结论血清NSE、ET和S-100B蛋白水平可作为急性脑卒中患者病情判断、预后评估的指标之一,尤其适用于无法进行影像学检查的脑卒中患者。     

不同麻醉用药对老年非体外循环冠脉搭桥术后认知功能影响的比较

目的:探讨适宜老年非体外循环冠状动脉旁路移植术(OPCABG)患者的麻醉用药方法。方法:择期拟行OPCABG的冠心病患者60例,年龄65～82岁,心功能Ⅱ级或Ⅲ级。随机分为七氟烷组(S组)和异氟烷组(I组),每组30例。于麻醉诱导后(T0)、术毕(T1)、术后6h(T2)和术后24h(T3)4个时间点采集颈内静脉球部血5mL,测定血清S-100蛋白和神经元特异性烯醇化酶(NSE)浓度。分别于麻醉前1d和术后3d、7d时对患者进行简易智能状态检查(MMSE)评分(总分30分),<24分为认知功能障碍。结果:术后所有患者镇痛效果均良好。术后7d内发生认知功能障碍者S组4例(13.3%),I组16例(53.3%),2组发生率差别有统计学意义(P<0.05)。2组术后3、7dMMSE评分均低于同组术前1d(P<0.05);I组术后7dMMSE评分低于S组(P<0.05)。2组血清S-100蛋白和NSE浓度于手术开始后升高,T1时达到高峰(P<0.05),T2下降,但仍高于基础值(P<0.05),至T3时恢复至基础水平(P>0.05);与I组比较,T1和T2时S组血清S-100蛋白和NSE浓度降低(P<0.05)。结论...     

重组人促红细胞生成素治疗急性脑梗死疗效观察

目的探讨重组人促红细胞生成素(rHu-EPO)治疗急性脑梗死患者近期的有效性和安全性。方法收集2018年2—8月我院神经内一科收治的急性脑梗死患者84例,随机分为EPO治疗组(n=43)与对照组(n=41)。两组均给予常规西药治疗,治疗组皮下注射rHu-EPO。观察两组患者第1、4、7、10、14天血清神经元特异性烯醇化酶(NSE)、S-100β蛋白变化,并比较治疗前后患者的美国国立卫生院卒中量表(NIHSS)评分、血压、血红蛋白变化。结果治疗后第7、10、14天两组患者血清NSE和S-100β蛋白均明显降低,EPO治疗组低于照组(P 0.05)。治疗14 d后EPO治疗组患者NIHSS评分低于对照组(P 0.05),两组血压、血红蛋白比较,差异无统计学意义(P 0.05)。结论 rHu-EPO能显著降低急性脑梗死患者血清NSE及S-100β蛋白含量,降低NIHSS评分,可以改善急性脑梗死患者的神经功能预后,可能对治疗急性脑梗死有效。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.