定志小丸对D-半乳糖致衰老模型小鼠学习、记忆能力及抗氧化活性的影响

目的研究定志小丸对D-半乳糖所致亚急性衰老小鼠学习记忆能力和脂质过氧化的影响.方法小鼠背部皮下注射D-半乳糖造成早衰模型,采用跳台法测小鼠学习记忆能力,血清和脑组织SOD、MDA.结果定志小丸使致D-半乳糖衰老小鼠跳台错误潜伏期显著延长,错误次数显著减少,血清和脑组织SOD 活力提高,MDA含量降低.结论定志小丸能改善D-半乳糖致衰小鼠的学习记忆功能,其机制可能与降低脑组织中脂质过氧化物的含量有关.     

定志小丸对 D-半乳糖致衰老模型小鼠学习、记忆能力及抗氧化活性的影响

目的研究定志小丸对D-半乳糖所致亚急性衰老小鼠学习记忆能力和脂质过氧化的影响。方法小鼠背部皮下注射D-半乳糖造成早衰模型，采用跳台法测小鼠学习记忆能力，血清和脑组织SOD、MDA。结果定志小丸使致D-半乳糖衰老小鼠跳台错误潜伏期显著延长，错误次数显著减少，血清和脑组织SOD 活力提高，MDA 含量降低。结论定志小丸能改善D-半乳糖致衰小鼠的学习记忆功能，其机制可能与降低脑组织中脂质过氧化物的含量有关。     

绿茶多酚对学习记忆障碍小鼠的改善作用及其机制

目的观察绿茶多酚(GTP)对D-半乳糖诱导的学习记忆障碍模型小鼠的药效,并初步探讨其机制。方法sc 120mg.kg-1.d-1D-半乳糖,建立学习记忆障碍模型小鼠;采用跳台法、水迷宫、避暗法和开场实验评价GTP对模型小鼠学习记忆障碍的改善作用,并测定小鼠血液和脑组织中乙酰胆碱酯酶(AchE)的活性。结果与学习记忆障碍模型组比较,GTP可明显延长跳台潜伏期,减少跳台错误次数;缩短游出迷宫的时间和减少进入盲端的错误次数;减少避暗活动错误次数和延长进入穿梭箱的潜伏期;同时,明显增加了小鼠的探究行为。低、中、高剂量的GTP对模型小鼠的脑组织及血清中AchE活性均无显著影响。结论GTP对D-半乳糖诱导的模型小鼠学习记忆障碍有改善作用,但此作用机制与AchE活性无关。     

当归芍药散二氯甲烷提取部位对D-半乳糖致衰老小鼠学习记忆能力的影响

目的研究当归芍药散二氯甲烷提取部位(DSP)对D-半乳糖(D-gal)致小鼠学习记忆能力障碍及神经毒性的改善作用。方法 ICR小鼠随机分为空白组,模型组,维生素E组,当归芍药散二氯甲烷提取部位低、高剂量组。空白组以外各组皮下注射D-半乳糖(50mg.kg-1.d-1)50d制备小鼠亚急性衰老模型。用跳台法和Morris水迷宫法评价小鼠的学习记忆能力,测定小鼠血清中总超氧化物歧化酶(T-SOD)、丙二醛(MDA)、谷胱甘肽过氧化酶(GSH-Px)活性和脑组织匀浆中谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)比值、Na+-K+-ATPase活性和淀粉样蛋白β(Aβ)含量。结果当归芍药散二氯甲烷提取部位能够显著提高衰老小鼠的学习记忆能力(P<0.05或P<0.01),提高衰老模型小鼠血清SOD、GSH-Px及脑组织Na+-K+-ATP酶活性,并升高GSH/GSSG比值,减少血清MDA(P<0.05或P<0.01);减少脑内Aβ含量(P<0.05)。结论当归芍药散二氯甲烷提取部位能够改善D-半乳糖衰老模型小鼠的学习记忆障碍,其作用可能与提高脑组织的抗氧化能力、降低中枢神经毒性有关。     

火麻仁油对D-半乳糖致衰老小鼠学习记忆障碍的保护作用研究

目的:研究火麻仁油对D-半乳糖(D-gal)致衰老小鼠学习记忆能力的保护作用,并探讨其作用机制.方法:采用D-半乳糖诱导小鼠衰老模型,用跳台法、水迷宫法和Morris水迷宫法测定衰老小鼠学习记忆能力,检测小鼠脑组织丙二醛(MDA)含量和总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及大脑皮层和海马组织中乙酰胆碱(Ach)含量和乙酰胆碱酯酶(AchE)、胆碱乙酰化转移酶(ChAT)活性,观察脑组织组织形态学变化.结果:火麻仁油(3、6和12 mL/kg)能明显延长跳台实验的跳台潜伏期,缩短错误次数;缩短水迷宫实验达到时间和减少错误次数;缩短Morris水迷宫实验逃避潜伏期和第1次到达原平台时间,增加穿越原平台次数和逗留时间;能显著增加脑组织中T-AOC、SOD、GSH-Px活性和降低MDA含量,增加大脑皮层和海马组织中Ach含量和AchE、ChAT活性,减轻脑组织损伤.结论:火麻仁油可显著改善D-半乳糖致衰老小鼠学习记忆能力,其机制可能与其提高脑组织抗氧化和清除自由基能力,增强中枢胆碱能神经系统功能有关.     

D—半乳糖致衰老小鼠记忆与海马突触形态学变化

目的探讨D-半乳糖致衰老小鼠学习记忆与海马突触界面结构可塑性变化的关系.方法用开场行为和Y-迷宫分辨学习记忆行为分别检测D-半乳糖衰老模型小鼠自发活动和学习记忆行为的变化,然后用电镜和计算机图象分析仪观测小鼠海马CA3区GrayⅠ型突触界面结构参数的变化.结果 D-半乳糖致衰老小鼠在新异环境中的自发活动和探究行为明显减少,学习记忆功能显著降低;记忆保持率(%)由76.8±9.3下降为68.6±9.4(P＜0.05);同时衰老小鼠出现海马突触后致密物质(PSD)厚度明显变薄(33.30±6.58,P＜0.01),突触间隙宽度显著增大(20.32±1.83,P＜0.05)等突触界面超微结构的改变.结论 D-半乳糖致衰老小鼠脑功能的减退可能与其改变海马突触界面超微结构有关.     

丹参红花提取物对D-半乳糖致衰老小鼠学习记忆的调节作用

目的观察丹参红花提取物对D-半乳糖(D-ga1)致小鼠衰老模型学习记忆的调节作用。方法小鼠随机分为正常对照组、模型对照组、丹参红花提取物低剂量(10 mg/kg.d)、中剂量(10 mg/kg.d)组、高剂量(10 mg/kg.d)组,8周后采用Y型迷宫、跳台实验检测小鼠学习记忆能力,及体内丙二醛(MDA)和超氧化物歧化酶(SOD)水平。结果与正常对照组比较,模型对照组小鼠跳台错误次数和迷宫错误次数明显增多;体内MDA含量升高,SOD活性下降;丹参红花提取物各组小鼠跳台错误次数减少,迷宫测试潜伏期缩短,体内MDA含量下降,SOD活性升高,并呈现剂量依赖性。结论丹参红花提取物能改善衰老小鼠学习记忆能力,其机制可能与抗氧化作用有关。     

松茸多糖对D-半乳糖所致小鼠衰老模型的影响

目的通过建立D-半乳糖致衰老小鼠模型,研究松茸多糖的抗衰老作用。方法实验小鼠随机分为5组,分别为正常对照组、模型组、Vit E(50 mg.kg-1)阳性对照组、松茸多糖低(10 mg.kg-1)、高(20 mg.kg-1)剂量组。在给药6周后,用小鼠跳台试验和Morris水迷宫实验测试小鼠的学习记忆能力;计算脑、胸腺及脾脏指数;检测小鼠血清及脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量。结果与模型组比较,松茸多糖低、高剂量组可明显提高衰老小鼠的学习和记忆能力,降低衰老小鼠的脑、胸腺及脾指数,还可不同程度提高衰老小鼠血清和脑组织SOD和GSH-Px活性,抑制MDA水平升高。结论松茸多糖可能通过提高机体免疫和抗氧化能力而发挥抗衰老作用。     

类叶升麻苷对D-半乳糖致衰老小鼠抗氧化作用的研究

目的 研究类叶升麻苷对D-半乳糖所致衰老小鼠的学习记忆能力和氧化作用的影响.方法 将昆明种小鼠随机分为空白对照组、模型组、石杉碱甲组和类叶升麻苷高、中、低剂量组.空白对照组颈背部注射生理盐水,其余各组颈背部注射D-半乳糖(150 mg·kg-1·d-1)造模,连续90 d.从第71天开始石杉碱甲组和类叶升麻苷低、中、高剂量组分别灌胃给药,连续20 d.采用Morris水迷宫测试小鼠的学习记忆能力,然后检测血清和脑组织内的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量.结果 与模型组相比,给予类叶升麻苷和石杉碱甲后可以改善小鼠的学习记忆能力,其潜伏期和游泳距离均明显缩短(P＜0.05).与空白对照组相比,模型组小鼠血清和脑组织内SOD、GSH-Px活性明显降低(P＜0.01),MDA含量明显升高(P＜0.01).与模型组相比,类叶升麻苷组在给药后均能明显提高小鼠血清和脑组织内SOD和GSH-Px活性(P＜0.01),降低血清和脑组织内MDA含量(P＜0.01).小鼠学习记忆能力与血清和脑组织内SOD、GSH-Px活性以及MDA含量相关(P＜0.01).结论 类叶升麻苷能够改善小鼠学习记忆功能,提高血清和脑组织内抗氧化酶活性,降低MDA含量.     

三才汤乙醇提取液对D-半乳糖衰老小鼠脑抗氧化作用的实验研究

为探讨三才汤抗衰老机理,本实验采用D-半乳糖衰老小鼠,灌胃三才汤醇提液30d,测定衰老小鼠脑SOD、NOS、Na+,K+－ATP酶活力和NO、MDA含量．实验结果表明,与模型组相比,三才汤醇提液能提高衰老小鼠脑SOD、NOS和NA+,K+－ATP酶的活性（P＜0.01和P＜0．05）,降低脑组织MDA含量（P＜0.01）,提高脑NO含量（P＜0．01）,提示三才汤醇提液对衰老小鼠脑有抗氧化作用,可延缓小鼠脑衰老。     

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.     

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.     

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.