健心灵口服液长期毒性实验研究

目的 :观察大鼠长期灌服健心灵口服液所产生的毒性反应的程度 ,以确定临床用药的安全性。方法 :大鼠灌胃给予三种浓度健心灵口服液 ,连续 6 0d ,末次给药 2 4h后处死动物 ,作血液学、血液生化学检查以及脏器系数测定 ,各组数据与对照组比较 ,各脏器作病理组织学检查。高剂量组、对照组余下动物放置 2周后 ,同样作上述检查与测定 ,了解该药的毒性反应。结果 :实验表明 ,健心灵口服液各剂量组动物体重及脏器系数与对照组比较无明显差异 ,中、小剂量组其血液学、血液生化学指标与对照组比较P >0 0 5 ;大剂量组动物血清ALT值与对照值比较P <0 0 5 ,其余指标均无明显差异 ;停药 2周后 ,其ALT值下降 ,各项指标与对照组比较P >0 0 5 ,各组动物病理组织学检查均无异常。结论 :健心灵口服液大剂量组动物连续 6 0d给药 ,其血清ALT值升高 (P <0 0 5 ) ,放置 2周后可恢复正常 ,说明该反应可逆 ,小、中剂量组及大剂量组动物血液学、血液生化学指标以及脏器系数与对照组比较无显著差异 (P >0 0 5 ) ,病理组织学检查无异常。通过大鼠长期毒性试验研究表明该制剂毒性在一定范围内较低 ,临床应用时应注意观察。     

健心灵口服液长期毒性实验研究

目的：观察大鼠长期灌服健心灵口服液所产生的毒性反应的程度，以确定临床用药的安全性。方法：大鼠灌胃给予三种浓度健心灵口服液，连续60d，末次给药24h后处死动物，作血液学、血液生化学检查以及脏器系数测定，各组数据与对照组比较，各脏器作病理组织学检查。高剂量组、对照组余下动物放置2周后，同样作上述检查与测定，了解该药的毒性反应。结果：实验表明，健心灵口服液各剂量组动物体重及脏器系数与对照组比较无明显差异，中、小剂量组其血液学、血液生化学指标与对照组比较P＞0．05；大剂量组动物血清ALT值与对照值比较P＜0．05，其余指标均无明显差异；停药2周后，其ALT值下降，各项指标与对照组比较P＞0．05，各组动物病理组织学检查均无异常。结论：健心灵口服液大剂量组动物连续60d给药，其血清ALT值升高(P＜0．05)，放置2周后可恢复正常，说明该反应可逆，小、中剂量组及大剂量组动物血液学、血液生化学指标以及脏器系数与对照组比较无显差异(P＞0．05)，病理组织学检查无异常。通过大鼠长期毒性试验研究表明该制剂毒性在一定范围内较低，临床应用时应注意观察。     

牛黄解毒滴丸毒理学实验研究

目的 观察牛黄解毒滴丸对小鼠的急性毒性和对大鼠90 d长期毒性.方法 取健康大鼠80只,完全随机分为对照组和小、中、大剂量组,各20只.对照组给等容量新制蒸馏水;小、中、大剂量组分别给予4.1、8.2、16.4 g/kg牛黄解毒滴丸,上午定时空腹灌胃给药1次,连续给药3个月.采用小白鼠最大耐受量测定法和大鼠长期毒性试验进行研究.结果 对小鼠灌胃给药的半数致死量＞9 g/(kg·d),相当于临床用量的120倍;停药后24 h大剂量组淋巴细胞高于对照组[(89±5)％比(84±4)％,P＜0.05],其他指标各组都在正常范围内;停药后2周,即恢复期,淋巴细胞即下降至正常范围内.停药后24h,中剂量组和高剂量组组大鼠的ALT、AST高于正常组[分别为(43±7)、(44±9) U/L比(35±9) U/L,(221 ±35)、(233±34) U/L比(197±35) U/L],停药后2周降至正常范围内.大鼠长期毒性试验对动物一般行为活动、体重增长和病理组织学检查等与对照组比较,差异均无统计学意义(P＞0.05).结论 牛黄解毒滴丸未见明显毒性,为临床安全用药提供了实验依据.     

藏药安儿宁颗粒毒理学研究

目的观察动物给予藏药安儿宁颗粒的急性毒性和长期毒性,确定无毒反应的剂量,以评估藏药安儿宁颗粒长期用药的安全性。方法急性毒性实验:采用小鼠最大耐受量灌胃法,24 h内灌胃3次,给药后连续观察14 d,记录小鼠的毒性反应及死亡情况;长期毒性实验:将96只大鼠按体重随机分为对照组和安儿宁颗粒高、中、低剂量组,每组24只,雌雄各半;各剂量组分别灌胃安儿宁颗粒90、30、9 g生药·kg-1(相当于临床日剂量的625、208.3、62.5倍),对照组灌胃等体积纯化水,1次·d-1,连续给药30 d,大鼠每周称重,给药结束时测试大鼠尿常规、血常规、血生化、脏器系数及病理组织学变化。结果小鼠1 d内3次灌胃藏药安儿宁颗粒的最大耐受量为90 g生药·kg-1,未见出现明显的急性毒性反应。长期毒性试验90 g生药·kg-1剂量组血液指标CREA、TP、BUN降低,TT升高;30 g生药·kg-1剂量组CHOL、CREA降低,APTT升高;9 g生药·kg-1剂量组CREA、BUN降低,其他指标与对照组比较均无统计学意义,这些现象在停药15 d消失。结论藏药安儿宁颗粒对小鼠灌胃无明显急性毒性反应。大鼠连续灌胃藏药安儿宁颗粒30 d,各剂量组对大鼠血液指标有轻度影响,停药后消失;无其他明显的慢性毒性反应和延缓毒性反应,临床用量是安全的。     

养阴益气胶囊长期毒性实验

目的 评价养阴益气胶囊对大鼠灌胃给药6个月的长期毒性情况。方法 90只SD大鼠随机分为3组：养阴益气胶囊大剂量组(每日灌胃给药剂量相当于生药20 g·kg^-1)、养阴益气胶囊小剂量组(每日灌胃给药剂量相当于生药5 g·kg^-1)和空白对照组(每日灌胃等容量纯化水),灌胃容量均为5 mL·kg^-1,给药时间均为180 d。观察指标为大鼠外观体征、进食、行为活动、排便、体质量、血液学及血生化指标,以及病理检查。停药后继续进行可逆性观察2周。结果 小剂量组和大剂量组大鼠体质量增加,但稍低于空白对照组(P>0.05);两组大鼠血液学指标均在正常范围内,与空白对照组之间差异无统计学意义(P>0.05);大剂量组血尿素氮高于空白对照组(P<0.05),但仍在正常范围内,其余血生化指标各组间差异无统计学意义(P>0.05)。各组动物系统尸解、组织病理学检查及可逆性观察均未见异常,脏器系数及生殖腺系数组间差异均无统计学意义(P>0.05)。结论 养阴益气胶囊给大鼠灌胃给药6个月的安全剂量为相当于生药20 g...     

五加双参片对大鼠的长期毒性研究

目的 观察大鼠长期口服五加双参片所产生的毒性反应及其程度，为确定临床用药的剂量提供科学依据。方法 采用大鼠灌胃给药90d，按体重和性别随机分为4．5g／kg、2．5g／kg、1．15g／kg3个剂量组和1个空白对照组，观察大鼠对药物的毒性反应。结果 3个剂量组与对照组动物在试验期间活动均正常，无一例死亡；体重增长情况基本一致，血常规、肝肾功能化验结果未见明显差异，主要脏器的病理解剖学和病理组织学检查未见特殊的病理学改变。结论 五加双参片是一种无明显毒性和副作用的纯中药制剂。     

QYL胶囊对大鼠的长期毒性试验

目的观察QYL胶囊对SD大鼠反复给药6个月的长期毒性作用,确定无毒性反应剂量,为临床用药提供安全性依据。方法采用SD大鼠以QYL胶囊提取物0.5、1.5和4.5g/kg体重连续灌胃6个月、停药恢复观察2个月的长期毒性试验。结果给药后期3个剂量组各有一只雄鼠先后死亡,病检显示低、中剂量组死亡雄鼠分别为肺部感染大叶性肺炎和灌胃受伤致死,高剂量组死亡雄鼠考虑为药物活血化瘀药效作用放大所致;中剂量组2只雌鼠精神欠佳、体重略降;中剂量组雄鼠和高剂量组动物体重增长缓慢,其余动物试验期间一般状况良好。给药期和停药恢复期中、高剂量组血液学、血液生化学虽有部分检查指标与对照组比较,差异有统计学意义,但均在本中心历史背景资料范围内小幅波动,且无明显剂量-反应关系,故无生物学意义。给药期中、高剂量组肝、肺、肾的重量及系数增加,可能与动物体重增长缓慢有关,停药2个月即有所恢复。恢复期中剂量一例、高剂量2例雄鼠镜检分别诊断为横纹肌肉瘤、平滑肌肉瘤和心脏血管肉瘤,与所给药物相关性不明确;其余动物主要器官、组织未见与药物明显相关的形态学改变。结论QYL胶囊0.50g/kg体重(推荐临床拟用药量的100倍)为基本无毒性反应剂量。     

心力丸的毒性试验研究

目的 观察心力丸对小鼠的最大耐受量(Maximal tolerance dose,MTD)和大鼠的长期毒性作用,为临床安全用药提供参考依据.方法 (1)最大耐受量的测定采用心力丸以最大剂量单次灌胃,观察给药后小鼠所产生的急性毒性反应和死亡情况.(2)长期毒性试验观察3个剂量组(0.4、0.2、0.1 g·kg-1·d-1)每天灌胃1次,每周给药6 d,连续给药3个月对大鼠产生的毒性反应.结果 (1)按40 ml/kg灌胃16%的心力丸混悬液,未见异常情况.(2)连续给药3个月各组动物一般状况无明显异常.结论 (1)心力丸的最大耐受量大于6.4 g/kg,是临床日用量的1600倍.(2)心力丸在0.4 g·kg-1·d-1,相当于临床最大日用量的100倍以下剂量是安全的.     

止消保肾宁颗粒的毒理学研究

目的:观察止消保肾宁颗粒对小鼠、大鼠的急性毒性和对大鼠的长期毒性。方法:给小鼠一次性灌胃不同剂量(33.0、29.8、26.9、24.3、21.9、19.8 g/kg)止消保肾宁颗粒,观察小鼠的一般情况及死亡数。给大鼠单次灌胃止消保肾宁颗粒13.2 g/kg,观察大鼠的急性毒性。在长期毒性实验中,给大鼠连续灌胃低、中、高剂量(3.1、6.2、12.4 g/kg)180 d,观察大鼠的体重、血液学指标、生化指标、脏器系数和组织病理学检查结果。结果:止消保肾宁颗粒对小鼠的LD50为26.0 g/kg。长期毒性实验中,第24～26周高剂量组大鼠体重增长较空白对照组明显减慢,第27周恢复。中、低剂量组大鼠的体重与空白对照组无显著性差异。高、中、低剂量组大鼠的血液学指标、生化指标、脏器系数与空白对照组无显著性差异。未发现与用药有关的组织病理学异常。结论:止消保肾宁颗粒的拟定临床剂量(190 mg/d)是安全的。     

咽康口服液急性毒性和长期毒性试验研究

目的 探讨咽康口服液的急性毒性和长期毒性,为临床安全用药提供科学依据。方法 急性毒性试验,在无法测定半数致死量(LD50)的基础上,以最大给药体积剂量(1.0 g/m L)给予小鼠炎康口服液,24 h内灌胃给药3次,连续观察7 d。长期毒性试验,将大鼠随机分为对照组及低、中、高[0.5,2.5,5.0 m L/(kg·d)]剂量组,给药量分别相当临床患者用药量的1,5,10倍;30 d后每组随机处死雌雄大鼠各5只,取尾静脉血测定血液流变学和血液生化学主要指标,对心、肝、肾、肺作组织病理学检查。结果 急性毒性试验时小鼠灌胃最大耐受量至少相当于临床1次治疗量的300倍,且未见毒性反应。长期毒性试验时各剂量组大鼠的体重和血液流变学、血液生化学主要指标与对照组无明显差异,心、肝、肾、肺组织病理学检查均未见明显病理改变。结论 咽康口服液临床应用安全。     

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.