连钱草乙醇提取物对豚鼠离体肠平滑肌和小鼠肠运动功能的影响

目的:观察连钱草乙醇提取物对小鼠小肠推进运动、药物性腹泻小鼠模型和豚鼠离体回肠平滑肌收缩的影响,探讨其作用机理.方法:采用在体方法观察连钱草乙醇提取物对小鼠小肠推进功能的影响,采用离体方法观察连钱草乙醇提取物对豚鼠回肠平滑肌运动功能的影响.结果:连钱草乙醇提取物能够显著抑制小鼠小肠炭末推进率(P＜0.01),缓解大黄所致小鼠腹泻 (P＜0.01),对抗新斯的明所致的肠蠕动亢进 (P＜0.01).抑制豚鼠离体回肠平滑肌收缩(P＜0.01),拮抗乙酰胆碱、组胺、氯化钡对离体豚鼠回肠平滑肌的激动作用(P＜0.01).结论:连钱草乙醇提取物具有抑制肠蠕动作用,这种作用可能由胃肠道的胆碱能受体和组胺受体介导,或直接作用于回肠平滑肌细胞.     

益智仁醇提取物对动物胃肠运动的影响

目的:研究益智仁醇提取物对动物胃肠运动的影响。方法:采用小鼠在体胃肠运动实验和家兔离体肠肌运动实验,观察益智仁醇提取物对正常小鼠胃排空、小肠推进运动和家兔离体肠肌收缩的影响。结果:益智仁醇提取物在5、10、20g·kg-1剂量下给药对正常小鼠胃排空有显著抑制作用,对家兔离体肠肌收缩有显著抑制作用,对氯化乙酰胆碱引起的肠肌兴奋有显著拮抗作用。结论:益智仁醇提取物对动物胃肠运动有抑制作用,其作用途径可能与M胆碱受体有关。     

粉防己碱对小鼠、家兔和豚鼠肠平滑肌的作用

目的　研究钙拮抗剂粉防己碱 (tetrandrine,Tet)对小鼠、家兔和豚鼠肠平滑肌的影响。方法　用小鼠胃肠推进运动法 ,家兔和豚鼠离体肠平滑肌标本。结果　 Tet(1 0～ 1 5 mg· kg-1,ig)对小鼠肠平滑肌运动无明显影响 ,Tet抑制家兔离体回肠自发性收缩 ,Tet(1 0 μmol·L-1)抑制氨甲酰胆碱诱导的豚鼠结肠带依内钙收缩 ,但不影响依外钙收缩。Tet浓度依赖性地使 KCl引起的豚鼠离体结肠带收缩量效曲线非平行右移 ,最大反应降低 ,p D2 为 4.0 1。结论　 Tet主要抑制肠平滑肌电压依赖性钙通道 (PDC) ,阻止 Ca2 + 通过 PDC,但对胃肠运动功能影响较小     

玄归滴丸对胃肠运动的抑制作用研究

目的探究玄归滴丸对不同机能状态小鼠胃肠运动和家兔离体肠管运动的影响,为其治疗平滑肌痉挛引起的腹痛提供实验基础。方法选择小鼠肠推进实验方法,利用新斯的明、阿托品等药物复制小鼠胃肠运动功能障碍模型,测定各组小鼠的胃残留率和小肠推进率;采用家兔离体肠管平滑肌实验,考察并记录给予不同受试药物后家兔离体肠管的肌张力变化。结果玄归滴丸临床等效4倍剂量、8倍剂量使正常小鼠胃残留率升高(P <0.05,P <0.01),小肠推进率降低(P <0.05);与正常对照组比较,新斯的明致小鼠胃肠运动亢进,给予玄归滴丸4倍剂量、8倍剂量组后能够明显地抑制胃肠运动,增加胃残留率(P <0.05,P <0.01),降低小肠推进率(P <0.01);与正常对照组比较,阿托品可致胃肠运动抑制,给予玄归滴丸4倍剂量、8倍剂量组后可以进一步抑制胃肠运动,进一步增加胃残留率(P<0.05,P <0.01),降低小肠推进率(P <0.05,P <0.01);家兔离体肠管平滑肌实验结果也进一步表明,玄归滴丸使家兔离体肠管的肌张力降低。结论玄归滴丸对胃肠运动具有一定的抑制作用,对痉挛性胃肠道疾病具有潜在的治疗效果。     

藿香正气滴丸对正常及乙酰胆碱刺激下动物胃肠道功能的影响

目的:观察藿香正气滴丸对正常及乙酰胆碱刺激下动物胃肠功能的影响。方法:观察藿香正气滴丸对正常小鼠胃排空和肠推进运动、乙酰胆碱所致大鼠离体胃底条平滑肌收缩、家兔离体肠平滑肌收缩作用以及家兔在体肠平滑肌收缩作用的影响。结果:藿香正气滴丸对正常状态胃肠运动无明显影响;可不同程度抑制乙酰胆碱引起的家兔在体回肠平滑肌收缩幅度以及乙酰胆碱所致大鼠离体胃底平滑肌以及家兔离体十二指肠平滑肌的收缩。结论:藿香正气滴丸对不同状态的胃肠道具有不同影响,对过度兴奋的胃肠道平滑肌收缩具有抑制作用,而对正常状态的胃肠道无明显影响。     

小儿健脾膏促胃肠动力作用研究

目的 观察小儿健脾膏对离体豚鼠回肠和大鼠胃肌收缩、在体大鼠胃肌收缩及整体小鼠胃排空与肠推进的影响。方法 离体和在体实验中,运用生物机能实验系统检测小儿健脾膏对回肠和胃肌收缩张力的影响;整体实验中,运用称重法和标记法测定小鼠胃排空率与肠推进比率。结果 离体实验中,不同剂量的小儿健脾膏均可增大豚鼠回肠和大鼠胃肌的平均收缩幅度;在体实验中,中、高剂量小儿健脾膏可显著增加大鼠胃肌的平均收缩幅度,且高剂量对大鼠胃肌的收缩与新斯的明具有协同作用;整体实验中,不同剂量的小儿健脾膏均能显著加速阿托品所致胃肠动力障碍模型小鼠的胃排空与肠推进。结论 小儿健脾膏具有促进胃肠动力的药理作用。     

款冬花不同提取物对豚鼠离体回肠收缩作用的研究

目的研究比较款冬花各个不同提取物对豚鼠离体回肠收缩的作用。方法通过石油醚、乙酸乙酯、CO2超临界萃取等方法制备款冬花多个提取物,将离体豚鼠回肠悬吊于克-亨试液中,观察给药后豚鼠回肠的收缩作用,计算豚鼠回肠收缩幅度抑制率。结果款冬花各个不同提取物均能降低组胺引起的豚鼠离体回肠收缩幅度。结论款冬花各个提取物能明显抑制豚鼠回肠收缩运动。     

款冬花不同提取物对豚鼠离体回肠收缩作用的研究

目的 研究比较款冬花各个不同提取物对豚鼠离体回肠收缩的作用。方法 通过石油醚、乙酸乙酯、CO2超临界萃取等方法制备款冬花多个提取物,将离体豚鼠回肠悬吊于克-亨试液中,观察给药后豚鼠回肠的收缩作用,计算豚鼠回肠收缩幅度抑制率。结果 款冬花各个不同提取物均能降低组胺引起的豚鼠离体回肠收缩幅度。结论 款冬花各个提取物能明显抑制豚鼠回肠收缩运动。     

法落海对小肠及子宫的作用

——用法落海根浸膏作药理实验,结果为:(1)给小白鼠灌胃,LD50为800±53毫克/公斤。(2)对肠鼠离体回肠的正常收缩有缓解作用,出现张力下降,收缩振幅变小或变平,并能对抗组织胺对豚鼠离体回肠的兴奋作用。(3)对家兔离体小肠的正常收缩有缓解作用,出现张力下降,收缩振幅变平,并能对抗乙酰胆硷对家兔离体小肠的兴奋作用。(4)原位家兔小肠实验,对小肠的正常收缩有缓解作用,出现张力下降,收缩振幅变小,并能对抗乙酰胆硷对原位小肠的兴奋作用。(5)对豚鼠离体子宫正常收缩有缓解作用,出现张力下降,收缩振幅变小或变平,并能对抗垂体后叶素或麦角新硷对肠鼠离体子宫的兴奋作用。(6)原位家兔子宫实验,对子宫的正常收缩有缓解作用,出现张力下降,收缩振幅变小,并能对抗垂体后叶索或麦角新硷对家兔原位子宫的兴奋作用。根据以上实验结果,提示法落海浸膏是一个平滑肌解痉药。     

木香超临界水提液对豚鼠离体肠和小鼠肠推动的作用研究

目的 观察木香超临界后水提液对小鼠小肠推进运动和豚鼠离体回肠平滑肌收缩的影响.方法 以正常、新斯的明负荷和肾上腺素负荷为研究模型,采用碳末推动法和离体肠实验方法.结果 木香Ⅰ组、木香Ⅱ组和木香Ⅲ组碳末推进率均高于正常对照组,差异有统计学意义(P<0.05和P<0.01).肾上腺素组碳末推进率明显低于正常对照组,差异有统计学意义(P<0.01);木香Ⅰ组、木香Ⅱ组和木香Ⅲ组碳末推进率明显高于肾上腺素组,差异有统计学意义(P<0.01).新斯的明组碳末推进率明显高于正常对照组,差异有统计学意义(P<0.01);木香Ⅰ组、木香Ⅱ组和木香Ⅲ组碳末推进率均低于新斯的明组,差异有统计学意义(P<0.05和P<0.01).给药后豚鼠自发收缩活动频率和振幅均高于给药前,差异有统计学意义(P<0.05和P<0.01),且振幅随着木香超临界水提液剂量的增加而增大.结论 木香超临界水提液有促进小鼠小肠运动的作用,对肾上腺素所致小鼠小肠推进抑制有显著的促进作用,对新斯的明所致的小鼠小肠推进亢进有拮抗作用,对豚鼠离体回肠自发活动有兴奋作用.     

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.