国产齐拉西酮的急性毒性作用的实验研究

目的：研究国产齐拉西酮灌胃(ig)给予和腹腔(ip)给药对NIH小鼠的急性毒性反应。方法：以0．5％羧甲基纤维素钠配制齐拉西酮悬液，小鼠灌胃给予和腹腔给予，观察指标包括给药后立即和连续14天观察小鼠的一般情况和计算半数致死量(LD50)。结果：齐拉西酮小鼠灌胃的LD50大于2．0g／kg。腹腔注射给药的LD50为1．407g/kg，95％可信限为1．167～1．697g／kg。结论：对于NIH小鼠，齐拉西酮灌胃给药、腹腔给药的LD50与国外产齐拉西酮的急性毒性相似。     

汉黄芩素的小鼠急性毒性作用研究

目的观察汉黄芩素对小鼠的急性毒性反应,评价其安全性大小。方法给小鼠灌服和腹腔注射不同质量浓度的汉黄芩素,观察小鼠的活动和毒性反应,记录小鼠的死亡数,并用Bliss法计算半数致死量(LD50)。结果汉黄芩素对小鼠经口服及腹腔注射的急性毒性症状主要有行动迟缓、异步态、心率加快、呼吸急促、连续性抽搐。小鼠口服给药的LD50为7.62 g/(kg.d),95%的可信限为6.55～8.86 g/(kg.d),腹腔给药的LD50为6.08 g/(kg.d),95%的可信限为5.89～6.27 g/(kg.d)。结论汉黄芩素毒性较低,该试验为其进一步开发应用提供了依据。     

司丙红霉素的急性毒性研究

目的:观察司丙红霉素对小鼠的急性毒性反应和死亡情况。方法:采用三种不同给药途径对昆明小鼠进行了急性毒性研究。结果:灌胃给药的LD50为2134.6(1761.8~2586.4)m g/kg,腹腔注射给药LD50为305.5(272.2~341.9)m g/kg,静脉注射给药LD50为121.2(115.3~127.3)m g/kg。结论:司丙红霉素用于临床是较安全的。     

熏硫对白芷提取物急性毒性的影响

目的:进行白芷提取物安全性评价,并比较熏硫与未熏硫白芷药材制备的提取物的急性毒性.方法:分别将熏硫与未熏硫的白芷药材制备的提取物分成5个不同的剂量组,观察小鼠灌胃给药后所产生的急性毒性反应的症状及死亡情况,并计算出该药所致的小鼠LD50及95％可信限.结果:测得未熏硫白芷药材制备的提取物的LD50为55.5169g生药/kg,95％可信限为49.3894～62.4046 g生药/kg;熏硫白芷药材提取物的LD50为89.4420 g生药/kg,95％可信限为79.1242～101.1052 g生药/kg.结论:熏硫与未熏硫白芷药材制备的提取物对小鼠急性毒性均属于无毒级,但熏硫后白芷药材制备的提取物的LD50及95％可信限明显升高,毒性明显降低.     

比伐卢定的升降压物质检查和毒性实验

目的:研究比伐卢定的升降压物质检查和毒性实验。方法:按照2010年版《中国药典》二部相关方法,以1⁵倍(2.85倍(2.8¹4mg/kg)临床单次用药剂量作为降压和升压物质检查剂量,采用猫血压法确定降压物质检查限值,采用SD大鼠总动脉插管监测血压确定升压物质检查限值;小鼠经尾静脉注射给药急性毒性实验测算其半数致死量(LD50),并确定异常毒性检查限值。结果:比伐卢定的降压、升压物质检查限值均为14 mg/kg;小鼠静脉注射的LD50为1.60 g/kg,LD50的95%可信限为1.5014mg/kg)临床单次用药剂量作为降压和升压物质检查剂量,采用猫血压法确定降压物质检查限值,采用SD大鼠总动脉插管监测血压确定升压物质检查限值;小鼠经尾静脉注射给药急性毒性实验测算其半数致死量(LD50),并确定异常毒性检查限值。结果:比伐卢定的降压、升压物质检查限值均为14 mg/kg;小鼠静脉注射的LD50为1.60 g/kg,LD50的95%可信限为1.50¹.71 g/kg;异常毒性检查注射给药后观察48 h,未见小鼠死亡。结论:比伐卢定符合《中国药典》要求。     

盐酸左氧氟沙星原料药的急性毒性作用研究

目的研究盐酸左氧氟沙星原料药的急性毒性作用,确保临床用药安全。方法选择静脉注射及腹腔注射两种途径作小鼠急性毒性试验,按Bliss法程序作统计处理。结果盐酸左氧氟沙星原料药对小鼠静脉注射的半数致死量（LD50）为399．93mg／kg,95％可信限为357．59～447．28mg／kg;腹腔注射LD50为1175．55mg／kg,95％可信限为1066．52～1259．73mg／kg。结论盐酸左氧氟沙星原料药毒性小,使用安全范围大。     

通脉丸方浓缩液的急性毒性实验

目的研究通脉丸方浓缩液的急性毒性。方法采用灌胃给药,观察小鼠的活动情况及死亡情况,测定通脉丸对小鼠的半数致死量（LD50）及可信限。结果给药后小鼠出现不同程度的中毒症状,小鼠死亡多发于4h之内,其灌胃给药LD50为107．48g／kg,其95％可信区间为96．624-117．71g／kg。结论通脉丸方浓缩液的急性毒性较小,毒性反应对雌雄小鼠没有差异。     

硫酸锌对小鼠半数致死量测定的可行性分析

目的探讨硫酸锌对小鼠半数致死量(LD50)测定的可行性。方法将60只小鼠随机分成6组,每组10只,分别按0.2437g/kg、0.3482g/kg、0.4973g/kg、0.7106g/kg、1.0150g/kg、1.4500g/kg质量浓度受试值以体质量(0.2m l/kg)给小鼠灌服不同浓度的硫酸锌溶液。观察小鼠的中毒症状及死亡情况。采用B liss法计算硫酸锌的LD50值及其95%的可信范围。结果给药后不同时间内小鼠出现活动受抑制,自由活动减少;濒死时出现呼吸困难、紫绀等症状;剖开腹腔可见胃肠道呈松弛膨胀,肝、肺充血等状态。硫酸锌的LD50为583.2mg/kg,LD50的95%平均可信限为(583.2±0.1528)mg/kg。结论明确了硫酸锌对小鼠LD50适宜剂量范围,为后续的实验研究工作提供了参考依据。     

杠柳毒苷单次给药的毒性研究

目的寻找小鼠灌胃给予杠柳毒苷的最大耐受量(MTD)、腹腔注射给药的半数致死量(LD50)和杠柳毒苷引起豚鼠半数出现心电异常的剂量。方法小鼠进行灌胃给药测定最大耐受量;小鼠进行腹腔注射给药测定半数致死量;豚鼠在清醒状态下腹腔注射不同剂量杠柳毒苷并连续观察其给药后心电图120 min,记录给药后心电异常数并计算其心电异常率。结果杠柳毒苷灌胃给药小鼠在66、83和103 mg/kg剂量下没有死亡;在20.65、17.55、14.92、12.68和10.78 mg/kg 5个剂量下,杠柳毒苷腹腔给药小鼠死亡率分别为100%、70%、60%、10%和0%;在0.58、0.46、0.37、0.30和0.24 mg/kg 5个剂量下,豚鼠心电异常率分别为80%、64.3%、30.8%、23.1%和7.7%。结论杠柳毒苷灌胃给药小鼠MTD为103 mg/kg;杠柳毒苷腹腔注射给药小鼠LD50为15.20 mg/kg;杠柳毒苷引起豚鼠半数出现心电异常的剂量为0.39 mg/kg。     

展舒胶囊急性毒性试验

目的：观察展舒胶囊的急性毒性,为临床安全用药提供依据。方法：用展舒胶囊进行小鼠灌胃和小鼠腹腔注射急性毒性试验。结果：小鼠灌服展舒胶囊最大浓度和最大容量,即40g·kg^-1体重,未见毒性发生;小鼠腹腔注射展舒胶囊LD50为0．86g·kg^-1体重,95％可信限为0．76～0．98g·kg^-1。结论：展舒胶囊按临床给药途径口服应用具有较高的安全性。     

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.