他克林优先拮抗4种莨菪类生物碱引起的小鼠学习障碍(英文)

目的:比较他克林(tacrine,50μmol·kg~(-1),sc)拮抗莨菪类生物碱(0.05-50μmol·kg~(-1),ip)所致学习记忆障碍。方法:用两次性开阔和回避反应研究,小鼠于第一次实验前30min给药。结果:他克林对东莨菪碱(Sco)0.05-50μmol·kg~(-1)或阿托品(Atr)5-50μmol·kg~(-1)引起的学习和记忆障碍均有拮抗作用,以拮抗学习障碍最明显。他克林能改善樟柳碱(AT_3)和山莨菪碱(Ani)5-50μmol·kg~(-1)所致学习损伤,但不能拮抗其记忆损伤。Sco 0.5-50μmol·kg~(-1),AT_3和Atr5-50μmol·kg~(-1)完全拮抗,Ani 50μmol·kg~(-1)部分拮抗他克林引起的自主活动减少。结论:他克林优先改善莨菪类药物引起的被动回避反应学习障碍。     

大鼠脑室注射四肽Asn-Ala-Gly-Ala引起的镇痛作用(英文)

icv四肽Asn-Ala-Gly-Ala(NAGA)能引起大鼠痛阈持续升高,并呈剂量依赖关系(0.03—0.24μmol/rat)。这一作用可被纳洛酮(icv.0.26mg·kg~(-1))翻转。icv甲硫氨酸脑啡肽抗血清或亮氨酸脑啡肽抗血清,能抑制NAGA引起的镇痛作用;icv强啡肽A_(1-13)抗血清或β-内啡肽抗血清不影响NAGA引起的镇痛作用。结果提示NAGA的镇痛作用可能与大鼠脑内甲硫氨酸脑啡肽和亮氨酸脑啡肽的释放有关。     

4-氨基吡啶诱发小鼠舔体反应与肥大细胞释放组胺

4-氨基吡啶(4-AP)1 mg·kg~(-1)颈背部sc能诱发小鼠舔体反应,该反应可被苯海拉明、氯苯那敏或阿司咪唑所抑制。重复注射 4-AP可使舔体反应逐渐减少或不发生,且给药部位皮肤组胺含量明显降低。4-AP也能促进小鼠离体腹腔肥大细胞释放组胺,结果表明,4-AP具有释放组胺作用,它诱发的小鼠舔体反应可能与释放组胺有关。     

脑室内注射4-氨基吡啶诱发家兔惊厥

家兔icv 4-氨基吡啶(4-AP)8μg能诱发反复发作的惊厥,ECoG呈现高幅棘波。抗癫痫药苯妥英钠、苯巴比妥钠、安定均能有效控制4-AP诱发的惊厥,使ECoG棘波消失。丙戊酸钠也有一定效果。东莨菪碱、氟哌啶醇与酚妥拉明均能拮抗4-AP引起的惊厥。结果提示,4-AP诱发的惊厥可能与它促进中枢ACh;DA及NE等递质的释放有关。家兔icv 4-AP诱发的惊厥与常用的癫痫模型比较,有一定优点,可作为筛选抗癫痫药的动物模型之一。     

S-21007,强效5-羟色胺3受体部份激动剂,对小鼠焦虑的作用(英文)

AIM: To study the effect of S-21007, a 5-HT_3partial agonist in different animal models of anxiety inmice. METHODS: S-21007 effects were evaluatedin the behavior tests after intraperitioneal and oral acutetreatment or in the light/dark test after both acute andchronic treatments. RESULTS: S-21007 presentedanxiolytic-like properties after acute administration inthe light/dark box test, the mirrored chamber test, andthe elevated plus-maze at be doses 10 ng·kg~(-1)-100μg·kg~(-1), 1-100 μg·kg~(-1) and 10-100 μg·kg~(-1),respectively. In the light/dark box test, S-21007 wasactive orally after acute treatment at 100 ng·kg~(-1)-10mg·kg~(-1) and after chronic treatment (14 d) at 1-10μg·kg~(-1). S-21007 was devoid of sedative or stimula-     

钙拮抗剂和钾通道开放剂对4-氨基吡啶诱发家兔惊厥的拮抗作用

家兔icy 4-氨基吡啶(4-AP)8μg 能诱发反复发作的惊厥,皮层电图(ECoG)呈现高幅棘波。钙拮抗剂尼莫地平(0.2 mg/kgiv)、氟桂嗪(5 mg/kg iv)及钾通道开放剂二氮嗪(0.1mg icv)均能有效控制4-AP诱发的惊厥,使ECoG 棘波消失。本文结果进一步证明钙拮抗剂与钾通道开放剂具有抗惊厥作用,并提示icv4-AP 诱发家兔的惊厥可能与该药阻滞神经细胞的钾通道有关。以4-AP 惊厥建立的筛选抗癫痫药的动物模型可能有其实用价值。     

单唾液酸四己糖神经节苷脂对小鼠便秘的调节作用研究

目的研究单唾液酸四己糖神经节苷脂(GM1)对小鼠便秘的调节作用。方法雄性SPF级ICR小鼠120只,分为正常对照组,模型对照组,空白制剂组,GM1低、中、高剂量组,每组20只,给药组连续7 d分别灌胃给予13、26、52 mg·kg~(-1)的GM1。末次给药后30 min通过灌胃给予5mg·kg~(-1)地芬诺酯片(每组10只),复制肠道蠕动抑制模型,观察小鼠肠道墨汁推进率;或灌胃给予10 mg·kg~(-1)的地芬诺酯片(每组10只)复制便秘模型,观察小鼠排便时间、排便粒数及排便重量。结果高剂量组GM1可显著提高肠蠕动抑制模型小鼠的小肠墨汁推进率;可显著缩短便秘模型小鼠首次排黑便的时间及增加排黑便粒数。结论 GM1对小鼠便秘具有明显的调节作用。     

双苯氟嗪对血小板聚集和血栓形成的影响(英文)

在体内外实验中观察我国首创合成的新钙拮抗剂双苯氟嗪(Dip)对血小板聚集和实验性血栓形成的作用。Dip iv 1—2mg·kg~(-1)和1—100μmol·L~(-1)体外温育可剂量或浓度依赖性地抑制ADP和AA诱发的家兔血小板聚集。Dip iv 2.5—10 mg·kg~(-1)和ip 50—100 mg·kg~(-1)可抑制大鼠体内血栓形成;Dip iv 10mg·kg~(-1)和200μmol·L~(-1)体外给药可抑制体外血栓形成。提示,减轻紊乱的血小板与血管壁反应是其抗血栓作用的主要因素,Dip的作用强于Cin。     

党参和甘草糖复合物对IEC-6细胞迁移和膜电位的影响

目的观察党参糖复合物和甘草糖复合物对小肠上皮细胞IEC-6迁移和细胞膜电位的影响,探讨益气健脾中药党参和甘草促进胃肠黏膜损伤修复的作用机制。方法在正常或钾通道抑制剂4-氨基吡啶(4-AP)负荷下,分别加入党参和甘草糖复合物(25~200 mg·L~(-1))与IEC-6细胞培养24 h,相差显微镜下观察细胞迁移数,流式细胞仪检测细胞膜电位。结果与细胞正常对照组比较,党参和甘草糖复合物(50和100 mg·L~(-1))可提高细胞迁移数(P<0.01,P<0.05)。与正常对照组比较,4-AP可减少细胞迁移数(P<0.01);与4-AP模型组比较,党参和甘草糖复合物(50~200 mg·L~(-1))可逆转4-AP所致的细胞迁移抑制(P<0.01)。流式细胞仪检测结果表明,与正常对照组比较,党参和甘草糖复合物(50 mg·L~(-1))可提高细胞膜电位(P<0.01),增加细胞膜超极化水平;与正常对照组比较,4-AP模型组细胞膜电位降低(P<0.01),增加细胞膜去极化水平;与4-AP模型组比较,党参和甘草糖复合物(100和200 mg·L~(-1))可逆转4-AP所致的细胞膜去极化(P<0.01)。结论党参和甘草促进胃肠黏膜损伤修复的作用机制,可能与其糖复合物影响小肠上皮细胞迁移的多胺介导钾通道激活信号通路有关。     

赛拉嗪对小鼠胃肠运动及大鼠胃肠电的影响

育亨宾(0.5～4mg·kg~(-1),sc)和苯口恶咪唑(2～8 mg·kg~(-1).sc)剂量依赖性地拮抗赛拉嗪(4mg·kg~(-1),sc)对小鼠胃肠推进运动的抑制作用.赛拉嗪(2、4 mg·kg~(-1),sc)可乐定(120μg·kg~(-1),sc)抑制大鼠胃、十二指肠、空肠、回肠的肌电活动,用药后30min作用最显著。育亨宾(4 mg·kg~(-1),sc)一定程度地拮抗赛拉嗪(4 mg·kg~(-1),sc)抑制胃肠肌电活动的作用.     

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.     

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.