不同钙拮抗药对大鼠杏仁核电刺激点燃模型的作用比较

目的 比较不同类型钙拮抗药对大鼠杏仁核电刺激点燃癫模型的作用及其机制。方法 采用恒定电流刺激大鼠右侧杏仁核制备大鼠杏仁核电刺激点燃慢性癫模型，观察不同类型的钙拮抗药对大鼠杏仁核电刺激点燃动物模型的后放电时程（ADD）和Racine’s分级的影响，并进行给药前后的自身对照。结果 不同类型钙拮抗药对大鼠杏仁核电刺激点燃癫发作的作用不同。尼莫地平40～80 mg·kg^-1 灌胃可抑制大鼠杏仁核电刺激点燃癫发作，降低Racine’s 分级（均P＜0.01）；地尔硫200 mg·kg^-1灌胃可抑制ADD（P＜0.05）,但对Racine’s 分级无影响（P＞0.05）;乙琥胺100～250 mg·kg^-1 灌胃对大鼠杏仁核电刺激点燃癫发作及Racine’s 分级均无抑制作用（均P＞0.05）；苯妥英钠20 mg·kg^-1 皮下注射可抑制大鼠杏仁核电刺激点燃发作，降低Racine’s分级（均P＜0.01）;丙戊酸钠500 mg·kg^-1 灌胃可抑制大鼠杏仁核电刺激点燃发作，降低Racine’s 分级（均P＜0.05）;桂利嗪20～60 mg·kg^-1灌胃可抑制大鼠杏仁核电刺激点燃癫发作，降低Racine’s 分级（均P＜0.01）。 结论 L型和T型钙通道可能参与癫发病机制，L型钙拮抗药尼莫地平具有抗癫点燃作用；较大剂量地尔硫可抑制ADD，其机制可能与阻滞L型电压依赖性钙通道（VDCC）有关; T型钙拮抗药乙琥胺对杏仁核癫点燃无抑制作用，杏仁核癫点燃发作或癫大发作与丘脑神经元低阈值T型钙通道无关；苯妥英钠、丙戊酸钠可抑制杏仁核点燃癫发作;苯妥英钠作用的T型钙通道不同于乙琥胺，该两药也可能通过其他机制抗癫;丙戊酸钠可能兼有乙琥胺和苯妥英钠对钙通道的抑制作用;桂利嗪的抗癫作用可能与阻滞多种类型的电压依赖性钙通道有关。     

MK-801与抗癫痫药合用对大鼠杏仁核点燃的影响(英文)

目的　在大鼠杏仁核点燃模型研究MK 80 1(地佐西平 )及其联合用药的抗癫痫作用。方法　建立大鼠杏仁核慢性电刺激点燃模型 ,测定不同剂量的MK 80 1对点燃模型各项指标的影响 ,探讨MK 80 1与其他抗癫痫药的协同作用 ,用氨基脲诱发的小鼠惊厥模型测定MK 80 1抗惊厥作用。结果　MK 80 1(0 1～ 0 2 5mg·kg- 1)可剂量依赖性抑制杏仁核点燃 ,缩短后放电时程 ,降低Racine’s分级 ;在对点燃均无明显影响的剂量下 ,MK 80 1(0 0 5mg·kg- 1)与抗癫痫药 (苯巴比妥、丙戊酸及尼卡地平 )合用可缩短后放电时程或降低Racine’s分级。MK 80 1(0 1～ 0 2 5mg·kg- 1)显著降低小鼠氨基脲诱发的发作潜伏期、惊厥发生率和死亡率。结论　MK 80 1具有抑制大鼠杏仁核点燃的作用 ,增强苯巴比妥、丙戊酸及尼卡地平的抗癫痫活性 ,为临床的合并用药提供实验依据     

东莨菪碱等对大鼠杏仁核点燃模型的影响

目的 :观察经常用于戒毒的药物东莨菪碱、可乐定和纳洛酮在杏仁核点燃模型中的作用 ,为戒毒药的开发研究寻找一种较好的药物筛选动物模型。方法 :制备大鼠杏仁核点燃模型 ,观察东莨菪碱对点燃发展及发作的影响 ,观察可乐定、纳洛酮对杏仁核点燃大鼠的影响。结果 :东莨菪碱 1 0 - 2 0mg·kg- 1 (ip)可抑制大鼠杏仁核点燃发展过程 (P <0 0 5 ) ;1 5 - 2 5mg·kg- 1 (ip)可抑制杏仁核点燃大鼠的发作 (P <0 0 5 )。可乐定 0 0 5 - 0 1mg·kg- 1 (ip)能降低点燃大鼠Racine’s分级 (P <0 0 5 )。纳洛酮对点燃模型无明显作用。结论 :东莨菪碱等经常用于戒毒的药物对点燃模型具有抑制作用 ,提示点燃模型对戒毒新药筛选可能有指导意义。     

尼卡地平对大鼠杏仁核点燃效应的抑制作用(英文)

目的:探讨钙通道阻滞剂尼卡地平对大鼠杏仁核点燃的作用及机制。方法:恒定电流每日一次刺激大鼠右侧杏仁核,观察尼卡地平对杏仁核点燃发展和发作的影响,测定点燃大鼠脑内各种氨基酸神经递质的含量。结果:腹腔注射尼卡地平2mg·kg~(-1)显著延缓杏仁核点燃发展进程(P<0.01);尼卡地平2-20mg·kg~(-1)剂量依赖性抑制大鼠杏仁核点燃发作,升高发作阈值(ADT),降低Racine分级;20mg·kg~(-1)尼卡地平显著提高杏仁核点燃大鼠脑内抑制性氨基酸神经递质GABA的含量(P<0.05)。结论:尼卡地平对大鼠杏仁核点燃的发展和发作有抑制作用,其机制可能与阻断电压依赖性钙通道及增强GABA系统功能有关。     

吲哚醌对大鼠杏仁核点燃的抑制作用

目的：研究吲哚醌对大鼠杏仁核点燃发作的影响及其抗惊厥作用。方法：建立大鼠杏仁核点燃模型,观察发作的电生理指标和行为学变化;在小鼠最大电休克惊厥、戊四唑惊厥和氨基脲惊厥模型计数惊厥发生率。结果： ip吲哚醌50～200 mg.kg-1均可升高杏仁核点燃大鼠的局灶性后放电阈值,降低发作强度和全身性发作 (stage 5) 百分率;可剂量依赖性地对抗小鼠最大电休克发作,并能取消戊四唑惊厥和氨基脲惊厥的强直相,降低戊四唑惊厥的死亡率。结论：吲哚醌对癫痫发作有抑制作用,其机制与抑制MAO-B活性、升高发作阈值有关。     

MK-801与抗癫痫药合用对大鼠杏仁核点燃的影响

目的在大鼠杏仁核点燃模型研究MK-801(地佐西平)及其联合用药的抗癫痫作用。方法建立大鼠杏仁核慢性电刺激点燃模型,测定不同剂量的MK-801对点燃模型各项指标的影响,探讨MK-801与其他抗癫痫药的协同作用,用氨基脲诱发的小鼠惊厥模型测定MK-801抗惊厥作用。 结果MK-801(0.1～0.25 mg·kg^-1)可剂量依赖性抑制杏仁核点燃,缩短后放电时程,降低Racine's分级;在对点燃均无明显影响的剂量下,MK-801(0.05 mg·kg^-1)与抗癫痫药(苯巴比妥、丙戊酸及尼卡地平)合用可缩短后放电时程或降低Racine's分级。MK-801(0.1～0.25 mg·kg^-1)显著降低小鼠氨基脲诱发的发作潜伏期、惊厥发生率和死亡率。结论MK-801具有抑制大鼠杏仁核点燃的作用,增强苯巴比妥、丙戊酸及尼卡地平的抗癫痫活性,为临床的合并用药提供实验依据。     

托吡酯对大鼠杏仁核点燃的抑制作用

目的　在大鼠杏仁核点燃模型研究抗癫痫新药托吡酯的抗癫痫作用及其作用机制。方法　建立大鼠杏仁核电刺激点燃模型 ,并通过联合用药探讨托吡酯对点燃的作用及其可能机制 ;测定托吡酯对小鼠氨基脲惊厥的影响。结果　托吡酯 (5 0～ 2 0 0mg·kg-1,ig)可剂量依赖性抑制杏仁核点燃 (P <0 0 5 )。在对点燃均无明显影响的低剂量下 ,托吡酯与丙戊酸钠或尼卡地平合用可缩短后放电时程 (P <0 0 5 )。托吡酯 2 0 0mg·kg-1,ig ,降低小鼠氨基脲诱发的惊厥发生率和死亡率 (P <0 0 1)。结论　托吡酯能抑制杏仁核点燃 ,与丙戊酸钠、尼卡地平有协同效应 ,其机制可能与GABA能神经功能增强以及Ca2 + 拮抗有关。     

氧化槐定碱对大鼠杏仁核脑区电活动及其功率谱的影响

目的 观察氧化槐定碱（oxysophoridine,OSR）对麻醉大鼠杏仁核脑区脑生物电（EEG）变化及其功率谱的影响 . 方法 利用脑立体定位技术,将电极置入大鼠杏仁核脑区,采用单极引导法及计算机辅助FFT技术记录并分析OSR对大鼠杏仁核脑区脑生物电变化的影响. 结果 每只大鼠侧脑室注射OSR 2.5,5.0,10.0 mg,大鼠杏仁核脑区出现以低幅慢波为主并伴有梭形睡眠波,总功率明显下降（P＜0.01）,主频率后移（P＜0.05）,α、β波占总频率比例升高（P＜0.05）. 结论 OSR具有中枢抑制作用,其抑制作用与降低大鼠杏仁核电活动、改变频率分配有关.     

托吡酯对大鼠点燃过程及杏仁核后放电的影响

目的观察托吡酯对大鼠点燃过程及杏仁核后放电的影响。方法选取雄性健康Wistar大鼠60只随机分为实验组及对照组各30只,实验组用托吡酯(40mg/kg)进行灌胃,用相同电刺激强度对两组大鼠进行点燃,记录点燃所需刺激次数、杏仁核后放电阈值、后放电时程及后放电频率。结果托吡酯(40mg/kg)灌胃后,实验组大鼠点燃总数明显减少,点燃所需刺激次数显著增加,杏仁核后放电阈值升高,时程缩短,后放电频率减少。结论托吡酯可明显抑制大鼠点燃过程,缩短杏仁核后放电时程和减少放电频率,升高杏仁核后放电阈值。     

利多卡因对电点燃模型的作用

目的研究利多卡因对电点燃模型的作用。方法采用腹腔注射的给药途径,观察杏仁核点燃大鼠的行为表现,以Racine分级作为评价标准。结果利多卡因0.5～25.0mg/kg腹腔注射可依赖性抑制大鼠杏仁核点燃作用,提高阈值,降低Rcine分级(P<0.01)。利多卡因剂量>30mg/kg,有明显的兴奋作用(P<0.05)。结论利多卡因对大鼠杏仁核点燃有兴奋和抵制双重作用。     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

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.