健脑合剂改善小鼠学习记忆作用及其机理初探

目的 :观察中药健脑合剂对记忆障碍小鼠学习记忆的影响 ,并初步探讨其作用机理。方法 :以跳台法、避暗法与电迷宫试验检测由东莨菪碱、亚硝酸钠及乙醇所致记忆障碍小鼠及D 半乳糖与三氯化铝模型小鼠的学习记忆能力 ,测定大脑胆碱酯酶活性、LPO含量与全血SOD活性。结果 :健脑合剂 1 4g·kg-1和 2 8g·kg-1可明显改善由东莨菪缄、亚硝酸钠及乙醇所致记忆获得、记忆巩固及记忆再现障碍 ,增强D 半乳糖模型小鼠与三氯化铝小鼠的被动学习能力 ,提高D 半乳糖所致衰老小鼠全血SOD活性及抑制脑LPO生成 ,显著降低痴呆小鼠脑胆碱酯酶活性。结论 :健脑合剂能提高记忆障碍模型小鼠及三氯化铝与D 半乳糖模型小鼠学习记忆功能 ,其机制可能与影响中枢M胆碱能系统和改善体内自由基平衡有关     

远志提取物对小鼠学习记忆的影响

目的:研究远志提取物(Ept-Ⅵ)对小鼠学习记忆功能的影响。方法:利用动物学习记忆计算机在线检测系统,采用东莨菪碱、亚硝酸钠、最大电休克和自然衰老所致小鼠学习记忆障碍模型,通过跳台试验和水迷宫实验对Ept-Ⅵ的益智作用进行了观察。结果:在跳台实验中,连续灌胃给予Ept-Ⅵ30～120 mg·kg-1·d-1,1周可明显改善12月龄BALB／C小鼠的学习和认知能力,使其在获得、巩固、再现阶段停留在安全区时间延长,错误区时间减少;连续灌胃给予Ept-Ⅵ60～240 mg·kg-1·d-1,2周对3 mg·kg-1·d-1东莨菪碱所致小鼠学习记忆障碍有明显的改善作用,表现为小鼠在学习巩固阶段安全区时间延长,错误区时间减少;而连续灌胃给予Ept-Ⅵ60～240 mg·kg-1·d-1, 2周可显著改善最大电休克(MES)所致小鼠学习记忆障碍。在水迷宫实验中,连续灌胃给予Ept-Ⅵ60～240 mg·kg-1·d-1,12周可以缩短亚硝酸钠所致学习记忆障碍小鼠到达水迷宫安全平台／出口的时间。结论:远志提取物能够在学习的多个阶段改善学习记忆障碍模型小鼠的学习记忆功能。     

抗衰灵口服液对小鼠学习记忆的改善作用

目的观察抗衰灵口服液对多种化学物质所致学习记忆障碍的影响。方法给予各种化学试剂造成小鼠学习记忆功能障碍 ,采用一次性被动回避反应跳台法和避暗法 ,以及方向辨别性水迷宫法观察受试药的改善作用。结果抗衰灵口服液能明显减少东莨菪碱所致获得性记忆障碍小鼠的错误次数、增强戊巴比妥钠引起的空间记忆障碍小鼠的学习记忆能力 ,对抗亚硝酸钠造成的小鼠记忆巩固不良和40 %乙醇引起的小鼠记忆再现障碍。结论抗衰灵口服液具有多方面改善智力的作用     

脑复康与氯酯醒配伍应用对学习记忆的改善作用

目的考察脑复康与氯酯醒配伍应用对学习记忆的改善作用。方法采用小鼠记忆获得、巩固、再现障碍模型,小鼠衰老模型以及大鼠痴呆模型,考察了两药配伍的药理学作用。结果脑复康与氯酯醒配伍以给药剂量为17.5和60 mg·kg-1,35和120 mg·kg-1连续腹腔注射2周,可以显著地改善东莨菪碱致小鼠记忆获得障碍和亚硝酸钠致小鼠记忆巩固障碍;也可显著改善乙醇致小鼠记忆再现缺失和半乳糖致小鼠记忆衰退;脑复康与氯酯醒配伍以给药剂量为12.25和42 mg·kg-1,24.5和84 mg·kg-1连续腹腔注射30 d可显著提高三氯化铝致大鼠主动回避与被动回避的达标率,显著降低大鼠海马内β淀粉样前体蛋白阳性神经元的数量。结论脑复康与氯酯醒配伍应用能够更好地改善学习记忆的衰退,降低海马β-APP阳性脑神经元的数量。     

异甘草素对丙泊酚致小鼠学习记忆障碍的影响

目的:研究异甘草素(isoliquiritigenin,ISL)对丙泊酚致小鼠学习记忆障碍的影响。方法:选用昆明种小鼠,随机分为5组,每组10只。ISL低、中、高剂量给药组分别灌服ISL 15、30、60mg.kg-1;正常照组和模型组每日灌服等容量的溶媒。灌胃60min后除正常对照组外,其他各组均腹腔注射丙泊酚20mg.kg-1。15min后测试避暗和跳下潜伏期及错误次数(避暗实验和跳台实验),以及10次测试中一次性正确的次数(Y迷宫法)。结果:与正常组比较,模型组避暗和跳下潜伏期缩短,错误次数增加,一次性正确次数减少;与模型组相比,异甘草素可剂量依赖性增加避暗和跳下潜伏期,减少错误次数,增加一次性正确的次数。结论:异甘草素可改善丙泊酚所致小鼠学习记忆障碍。     

不同用量配伍当归芍药散对动物学习记忆功能及脑内NO的影响

目的:研究不同用量配伍当归芍药散对动物学习记忆功能及脑内神经化学物质NO的影响。方法:用避暗法和水迷宫法测定小鼠的学习记忆功能,脑内NO的测定参照试剂盒方法进行。结果:不同归芍比的当归芍药散对正常小鼠的学习记忆能力都有一定的促进作用,其中归芍比为15.4、11.34的组方能明显改善东莨菪碱所致小鼠被动回避障碍,明显延长小鼠潜伏期,减少错误次数;在改善小鼠空间辨别障碍方面,归芍比为11.34的当归芍药散能明显缩短利血平化小鼠水迷宫潜伏期,改善小鼠空间辨别障碍,其余各组方对正常小鼠水迷宫潜伏期影响不明显;而不同归芍比的当归芍药散能降低东莨菪碱所致的被动回避障碍小鼠脑内NO含量升高。结论:当归芍药散中归芍比为11.34时,既能明显改善小鼠被动回避障碍,又能明显改善小鼠空间辨别障碍,降低东莨菪碱所致的被动回避障碍小鼠脑内NO含量的升高,益智作用最佳。     

抗衰灵口服液对小鼠学习记忆的改善作用

目的 观察抗衰灵口服液对多种化学物质所致学习记忆障碍的影响。方法 给予各种化学试剂造成小鼠学习记忆功能障碍，采用一次性被动回避反应－－跳台法和避暗法，以及方向辨别性水迷宫法观察受试药的改善作用。结果 抗衰灵口服液能明显减少东莨菪碱所致获得性记忆障碍小鼠的错误次数、增强戊巴比妥钠引起的这间记忆障碍小鼠的学习记忆能力，对抗亚硝酸钠造成的小鼠记忆巩固不良和40％乙醇引起的小鼠记忆再现障碍。结论 抗衰灵口服液具有多方面改善智力的作用。     

石菖蒲水提取物SIPI-SCPd改善动物学习记忆的研究

目的研究石菖蒲水提取物SIPI-SCPd是否有改善动物学习记忆的作用。方法将70,35,17.5和8.75 mg/kg的SIPI-SCPd分别连续给予ICR小鼠口服2周或Wistar大鼠口服4周,采用跳台法或避暗法观察其对东莨菪碱、NaNO2及45%乙醇诱导的小鼠记忆损伤(记忆获得障碍,记忆巩固不良,记忆再现障碍)模型的影响,以及采用Morris水迷宫法观察SIPI-SCPd对由东莨菪碱所致大鼠记忆障碍的影响。并观察受试小鼠脑内乙酰胆碱酯酶活力的变化。结果 70,35,17.5 mg/kg的SIPI-SCPd均能延长记忆获得障碍、记忆巩固不良和记忆再现障碍模型小鼠跳下平台或进入暗室的潜伏期;并能改善由东莨菪碱所致的大鼠空间记忆障碍。SIPI-SCPd对乙酰胆碱酯酶的活性没有影响。结论 SIPI-SCPd对几种药物诱导的记忆障碍模型动物的学习记忆功能均有一定的改善作用,且该作用与乙酰胆碱酯酶的活性无关。     

脑清宁颗粒剂对小鼠学习记忆能力的影响

目的观察脑清宁颗粒剂对小鼠学习记忆能力的影响.方法以东莨菪碱、亚硝酸钠和乙醇分别造成小鼠记忆获得障碍、记忆巩固障碍和记忆再现障碍,采用Y型迷路法测定小鼠学习记忆能力.结果在3种记忆障碍模型中,预先灌胃给予脑清宁颗粒剂5、10、20 g·kg-1,1次·d-1,连续7 d,可明显提高小鼠的学习记忆成绩(P＜0.001).结论脑清宁颗粒剂对小鼠学习记忆障碍有改善作用.     

抗痴Ⅰ号对小鼠学习和记忆的促进作用

采用复杂食饵迷宫法和一次训练被动回避性条件反应—跳台法,观察了抗痴I号对小鼠学习和记忆的促进作用。实验结果表明抗痴I号对正常小鼠的空间辨别学习、记忆获得方面有促进作用;可拮抗东莨菪碱造成的记忆获得障碍;改善氯霉素和亚硝酸钠造成的记忆巩固不良;改善30％乙醇引起的记忆再现缺损,并对亚硝酸钠中毒缺氧有明显的改善作用。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.