润燥颗粒对小鼠小肠推进功能的实验研究

目的:评价润燥颗粒对小鼠小肠推进功能的影响。方法:观察该药混悬液对阿托品、肾上腺素、盐酸吗啡负荷小鼠以及正常小鼠小肠推进运动的影响,并用t检验分析。结果:该药的3个剂量组与对照组相比较,P均小于0.01。结论:润燥颗粒促进4种不同负荷的小鼠小肠推进功能作用显著,并具有明显的量效关系。     

增液汤颗粒对便秘小鼠的润肠通便作用

目的 研究增液汤颗粒的润肠通便作用。方法 采用复方地芬诺酯建立小鼠便秘模型,观察便秘小鼠的粪便排泄情况、肠水分和小肠推进运动等指标;观察正常小鼠的大肠推进运动;采用在体肠管实验法研究正常大鼠回肠收缩活动和对正常小鼠肠道肠液分泌量的影响。结果 增液汤颗粒能够缩短便秘小鼠首次排便时间,增加便秘小鼠粪便粒数（P〈0.05或P〈0.01）,改善粪便性状,增加便秘小鼠肠水分（P〈0.05或P〈0.01）,增强便秘小鼠的小肠推进运动,增强正常小鼠的大肠推进运动,促进正常大鼠回肠收缩,增加正常小鼠肠腔液体量（P〈0.05或P〈0.01）。结论 增液汤颗粒具有较好的润肠通便作用,能够有效治疗便秘。     

小儿便通颗粒泻下通便作用的实验研究

目的研究小儿便通颗粒的泻下通便作用。方法选择正常小鼠小肠推进试验,阿托品所致小鼠小肠抑制试验,小鼠胃排空肠推进模型及正常小鼠排便试验,自身粪便所致便秘模型,失水性便秘模型,对小儿便通颗粒的药理作用进行评价。结果小儿便通颗粒可以促进正常小鼠小肠蠕动;对抗小鼠因阿托品所致小鼠小肠抑制状态;增加食物在胃中的排空作用和肠道中的推进率;缩短正常小鼠的排便时间,增加排便量和粒数,水分吸引减少;对因食自身粪便和失水造成的便秘模型具有一定的治疗作用。结论小儿便通颗粒具有一定的泻下通便作用,为该药治疗小儿便秘提供了实验依据。     

番泻苷对小鼠肠道运动功能的影响及相关机制研究

目的 :评价大黄提取二蒽酮类衍生物 (番泻苷 ,sennoside ,SEN)对小鼠肠道运动功能的影响 ,并探讨其相关机制。方法 :采用小鼠湿粪记数试验观察番泻苷对小鼠肠道运动功能的影响 ;采用放射免疫分析法检测小鼠小肠组织胃动素 (motilin ,MTL)、生长抑素 (somatostatin,SS)的水平 ;采用分光光度法测定小肠粘膜Na K ATP酶的活性。结果 :番泻苷各剂量均能增强小鼠的排便功能 ,与正常对照组相比有显著差异 ;番泻苷各剂量均能显著提高小鼠小肠组织胃动素的含量 ,而降低生长抑素的水平 ;番泻苷各剂量组小鼠小肠粘膜Na K ATP酶活性显著低于正常对照组。结论 :番泻苷能增强小鼠的肠道运动功能 ,具有润肠通便之功效 ,其机制可能与促进肠道胃动素释放 ,降低肠道生长抑素水平和抑制小肠粘膜Na K ATP酶的活性有关     

夏黄颗粒治疗慢传输型便秘的实验研究

目的 采用吗啡致小鼠慢传输型便秘模型,评价夏黄颗粒的治疗作用,并对其通便作用进行实验研究。方法 采用连续sc 2.5 mg/kg盐酸吗啡45 d致小鼠慢传输型便秘模型,观察夏黄颗粒的通便作用;采用1次性ip 5 mg/kg盐酸吗啡致小鼠小肠推进、胃排空抑制模型,观察夏黄颗粒对胃肠抑制的拮抗作用;采用测定小鼠小肠湿、干质量法,观察夏黄颗粒对肠水分吸收的作用;采用顺铂致大鼠异嗜模型,观察夏黄颗粒的止吐作用;采用吗啡致豚鼠离体回肠、结肠痉挛模型,观察夏黄颗粒的作用及机制。结果 与模型组比较,小鼠给药5 d,夏黄颗粒14.95、7.48 g生药/kg能显著增加慢传输型便秘小鼠的24 h排便量（P<0.05、0.01）,继续给药至7 d,14.95、7.48 g生药/kg能显著增加小肠推进率、14.95 g生药/kg显著升高血清P物质含量（P<0.05、0.01）;给药1次,14.95、7.48 g生药/kg剂量组能显著增加小鼠小肠推进率、加快胃排空（P<0.01）,14.95 g生药/kg显著增加小鼠小肠含水量（P<0.01）;大鼠给药3 d,10.35 g生药/kg剂量组能显著降低大鼠异嗜高岭土质量（P<0.05）;给药1次,2.49、1.25 mg生药/mL（浴槽终浓度）能显著降低吗啡所致痉挛性回肠的肠张力（P<0.01）,2.49、1.25、0.62 mg生药/mL（浴槽终浓度）能显著降低吗啡所致痉挛性结肠的肠张力（P<0.05、0.01）。结论 夏黄颗粒对吗啡所致慢传输型便秘有显著的治疗作用,具有显著的通便、解痉、促进胃肠运动、肠吸收及止吐作用。     

气滞胃痛颗粒促进胃肠运动和镇痛作用研究

目的：观察气滞胃痛颗粒对小鼠胃肠动力的影响和镇痛作用,为气滞胃痛颗粒的临床合理应用提供理论依据。方法：以胃肠内标记物葡聚糖蓝-2000在小鼠胃内色素残留及小肠内推进比为指标,观察气滞胃痛颗粒对小鼠胃排空及肠推进的影响;以醋酸所致小鼠扭体反应为疼痛指标,观察气滞胃病颗粒的镇痛作用。结果：气滞胃痛颗粒低、中、高剂量组（1．25g／kg、2．50g／kg、5．00g/kg）可以改善阿托品和多巴胺引起的小鼠胃排空障碍、以及小肠推进抑制作用;对吗啡引起的小鼠胃排空障碍和小肠推进抑制作用无显著影响;中、高剂量组可以促进正常小鼠胃排空,高剂量促进小肠推进。低、中、高剂量组可以显著减少醋酸引起的小鼠扭体次数。结论：气滞胃痛颗粒具有促进小鼠胃肠动力和镇痛作用。     

小鼠低纤维膳食便秘模型的初步研究

目的通过给予小鼠特制低纤维饲料,建立小鼠低纤维膳食便秘模型,并采用富含膳食纤维的样品进行模型验证。方法设5个组:普通饲料阴性对照组、低纤维饲料模型组(Low-fiber-diet,LFD)和高纤样品3个剂量组(146. 75,1 467. 5和4 402. 5 mg/kg·bw)。每组20只小鼠,10只用于小肠运动试验,另10只用于排便试验。普通饲料阴性对照组5周内持续给予普通饲料,第22天开始给予蒸馏水; LFD组5周内持续给予低纤维饲料,第22天开始给予蒸馏水;高纤样品3个剂量组5周内持续给予低纤维饲料,第22天开始给予小鼠相应剂量样品。所有动物经口灌胃1次/d,共14 d;试验第36天进行小肠运动试验和小鼠排便试验。结果小肠运动试验结果显示:LFD组与阴性对照组小鼠比较、高纤样品各剂量组与LFD组比较,小鼠小肠推进率差异均无统计学意义(P0. 05)。小鼠排便试验结果显示:LFD组与阴性对照组比较,6 h排便粒数减少、粪便湿重降低、粪便干重降低且排便时间延长,差异均有统计学意义(P0. 01),提示模型成立。高纤样品低剂量组与LFD组比较,排便时间缩短(P0. 01);其他参数比较差异无统计学意义(P0. 05)。高纤样品中、高剂量组与LFD组比较,6 h便粒数增加、粪便湿重增加、粪便干重增加且排便时间缩短,差异均有统计学意义(P0. 01)。结论小鼠排便试验低纤维膳食便秘模型成立,给予高纤样品后可改善小鼠便秘情况,具有润肠通便的功能。在小肠运动试验中,低纤维膳食便秘模型不成立可能与其便秘机制与试验原理不一致有关,尚需进一步研究。     

干酪菌发酵产物对小鼠小肠推进功能抑制的影响

目的观察干酪菌发酵产物对小鼠小肠推进运动抑制的影响。方法采用小鼠小肠推进实验 ,观察经胃给予干酪菌发酵产物前后小肠推进百分比的变化 ,以及腹腔注射几种胃肠运动抑制剂后对其药效的影响。结果干酪菌发酵产物 (1 5 0、30 0、6 0 0mg/kg)能提高小鼠小肠推进百分比 ,且呈剂量 效应依赖关系 ;能拮抗多巴胺 (1mg/kg)、吗啡 (8mg/kg)、肾上腺素 (0 .1mg/kg)引起的小鼠小肠运动减弱。结论干酪菌发酵产物能提高小鼠小肠推进功能 ;能改善小鼠小肠运动抑制     

新生颗粒的药效学实验研究

目的:观察及评价新生颗粒的主要药效。方法:采用化学刺激镇痛实验研究新生颗粒的镇痛作用;采用排便实验研究新生颗粒对硫酸阿托品致胃肠麻痹模型的胃肠运动作用;戊巴比妥钠阈剂量实验研究新生颗粒的催眠作用;吗啡依赖自然戒断实验研究新生颗粒对吗啡依赖大鼠自然戒断后体重下降的影响。结果:新生颗粒中、高剂量组对化学刺激所致疼痛具有明显的抑制作用(P<0.01),尤以高剂量组作用明显(P<0.001);新生颗粒中剂量组、高剂量组可显著地延长阈剂量戊巴比妥钠小鼠睡眠时间(P<0.001);对抗阿托品引起的胃肠平滑肌蠕动减慢所致的排便时间延长、排便量减少等症状,可显著缩短排便时间和增加排便量(P<0.01),具有明显增强胃肠推进作用;能抑制吗啡自然戒断大鼠体重下降(P<0.001、P<0.01或P<0.05),对吗啡依赖动物的戒断反应表现出明显的抑制作用。结论:新生颗粒具有一定的镇痛、催眠、增进胃肠动力作用及吗啡戒断体重下降抑制作用,对吗啡戒断综合征具有一定的治疗作用。     

无毒棉籽液抗腹泻作用机理

小鼠灌胃给予无毒棉籽３，６ｇ／ｋｇ对蓖麻油、硫酸钠致腹泻有拮抗作用，对正常小鼠及生大黄泻下鼠的肠腔水分无影响；对新斯的明、酚妥拉明所致小肠运动亢进有明显抑制作用，对阿托品致小肠运动减弱有协同作用．无毒棉籽抗泻下的机制可能与抑制副交感神经的兴奋有关     

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.     

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.