油茶皂苷对小鼠经口、经腹腔急性毒性试验

目的观察油茶皂苷（sasanquasaponin．SQS）对小鼠经口、经腹腔急性毒性,计算其半敷致死量（LD50）。方法给小鼠灌服和腹腔注射不同浓度的SQS溶液,通过观察小鼠的活动和毒性反应,记录小鼠的死亡数,用Bliss法计算LD50。结果给药后不同时间内,小鼠出现自由活动减少,濒死时呼吸频率加快、张口呼吸、鼻翼扇动等中毒症状,死亡高峰在6h内,死亡原因为多脏器损伤。小鼠经口LD50=1999．3mg·kg^-1,95％的可信限=1645．2-2440．2mg·kg^-1,腹腔给药LD50=36．525mg·kg^-1,95％的可信限=29．773-45．408mg·kg^-1.结论SQS属于低毒物质。     

来氟米特3-甲基异构体急性毒性试验

目的观察来氟米特3-甲基异构体经口给药的急性毒性试验（LD50的测定）。方法给小鼠灌服不同浓度来氟米特3-甲基异构体混悬液,通过观察小鼠的活动和毒性反应,记录小鼠的死亡数,用Bliss法计算LD50。结果动物给药后不同时间内很快表现为兴奋,继而动物出现抽搐,后精神差,静伏少动,步态蹒跚,濒死时精神极差,呼吸频率加快、张口呼吸、鼻翼扇动等中毒症状。LD50=1537mg.kg-1,95%的可信限=1252.3～1879.8mg.kg-1,LD5=646.99mg.kg-1,LD95=3651.3mg.kg-1。结论来氟米特3-甲基异构体急性毒性很小。     

不同粒径马钱子粉的急性毒性实验

目的通过运用超细粉碎技术,观察普通马钱子粉与超细马钱子粉对小鼠的急性毒性实验.方法运用急性毒性实验方法,所得数据用“改良寇氏法”计算.结果普通马钱子粉LD50为223.95mg*kg-1,95%的可信限为208.19～240.94mg*kg-1;超细马钱子粉LD50为198.09mg*kg-1,95%可信限181.41～216.34mg*kg-1.结论马钱子粉经超细粉碎后可增加其在体内的吸收.     

丹酚酸B对小鼠的急性毒性试验

目的进行丹酚酸B小鼠急性毒性研究,为新药开发和安全用药提供参考。方法小鼠尾静脉注射不同剂量的丹酚酸B原料,连续观察14 d,记录小鼠的急性毒性反应,并计算半数致死量(LD50)以及LD5095%可信限。结果尾静脉注射给药后,部分小鼠出现毒性反应并死亡,计算LD50为636.890 9 mg·kg-1,LD5095%的可信限为617.225 5～657.182 8 mg·kg-1,死亡动物尸检,各主要脏器肉眼未见明显改变,14 d后各剂量组存活小鼠体重均增加。结论丹酚酸B原料毒性较小。     

盐酸氯雷他定一般药理学及毒理学实验研究

目的观察盐酸氯雷他定的一般药理试验及急性毒性试验,以证明其安全性。方法采用多计量盐酸氯雷他定对不同动物进行一般药理学及毒理学试验。结果小鼠灌胃给予5mgkg-1、10mgkg-1和20mgkg-1盐酸氯雷他定对小鼠的自主活动和给予阈下催眠剂量戊巴比妥钠的小鼠入睡的数目均无明显影响。十二指肠给予1.5mgkg-1、3.0mgkg-1和6.0mgkg-1盐酸氯雷他定对麻醉猫的心血管和呼吸系统亦无明显影响。小鼠灌胃给予盐酸氯雷他定,LD50=1373.85mg.kg-1(95%可信限1114.61～1646.66mg.kg-1);小鼠腹腔注射给盐酸氯雷他定,LD50=527.96mg.kg-1(95%可信限446.22～625.29mg.kg-1)。     

香加皮不同组分对小鼠急性毒性实验比较研究

目的比较进行香加皮全组分、水提组分、醇提组分的急性毒性观察与评价,为临床用药的安全性提供依据。方法分别制备香加皮上述不同组分,按照经典小鼠急毒试验方法,用bliss法计算半数致死量（LD50）,公斤体重法计算最大耐受量（MTD）,考察香加皮全组分（MTD）值、水提组分（LD50）值、醇提组分（LD50）值,连续给药观察14天,记录各组动物体重变化,毒性症状谱及死亡情况。结果香加皮药材全组分MTD可达16.0g.kg-1.d-1,相当于临床人用量的186.6倍;香加皮水提组分LD50值为93.578g.kg-1.d-1,95%的可信限为89.149～98.484g.kg-1.d-1,相当于临床人用量的1091.8倍,香加皮醇提组分LD50值为61.388g.kg-1.d-1,95%的可信限为57.466～65.521g.kg-1.d-1,相当于临床人用量的716.2倍。通过小鼠急毒实验观察：肢体麻痹、腹泻、抽搐、呼吸抑制是香加皮不同组分主要的急性毒性症状,香加皮水提、醇提组分小鼠死亡多发生于48小时之内。结论香加皮不同组分毒性大小顺序依次为醇提组分、水提组分、全组分。     

柴胡总皂苷粗提取物对小鼠急性毒性实验研究

目的探讨柴胡总皂苷提取物对小鼠急性毒性的影响。方法采用经典的小鼠急性毒性试验方法,进行柴胡总皂苷粗提取物对小鼠的急性毒性研究。结果按含生药量计算,柴胡总皂苷粗提取物对小鼠的半数致死量（LD50）为94.974g·kg-1·d-1,相当于临床70kg成人每公斤人日用量的422.8倍;95%可信限为88.742～103.76g·kg-1·d-1,相当于临床70kg成人每公斤人日用量的414.1～484.2倍;按含总皂苷含量计算,LD50为5231.5mg·kg-1·d-1,95%可信限为4886.1～5721.2mg·kg-1·d-1。死亡小鼠急性毒性主要表现为安静怠动,即而出现走路不稳、腹卧昏睡、心率加快、呼吸急促、连续性抽搐、神经抑制而死亡。存活小鼠在14天观察期内体重增长缓慢,余未见明显异常。结论柴胡药材具有一定的毒性,与临床报道相一致。柴胡总皂苷既是其发挥功效的主要化学成分,又是其产生毒性的主要物质基础。其毒性部位以及体内蓄积毒性的＂量-时-毒＂关系有待进一步研究。     

桦褐孔菌不同提取物小鼠急性毒性实验研究

目的研究桦褐孔菌不同提取物对小鼠急性毒性作用,为临床安全用药提供依据。方法采用经典的急性毒性实验方法,测定桦褐孔菌水提物和70%乙醇提取物的半数致死量(LD50),并观察其毒性反应。结果随着给药量的增大,桦褐孔菌水提物和醇提取物对小鼠毒性作用逐渐增强,死亡率逐渐升高,空白组没有异常变化。按生药量计算水提物的LD50是17.49g·kg-1,95%可信区间为16.36～18.70g·kg-1;醇提取物LD50是61.97g·kg-1,95%可信区间为53.73～71.46g·kg-1。结论桦褐孔菌水提物和70%乙醇提取物均有一定的毒性,且水提物毒性起效量比70%乙醇提取物的起效量小。     

白首乌C_（21）甾总苷及其醋酸降解产物的急性毒性试验研究

目的比较白首乌C21甾总苷及其醋酸降解产物对小鼠急性毒性的影响。方法分别以1∶0.8等比稀释法配制等比浓度白首乌C21甾总苷组及白首乌总苷醋酸降解产物组的给药剂量,一次性腹腔给药,观察小鼠的死亡率,采用改良寇氏法计算半数致死量（LD50）。结果白首乌C21甾总苷的LD50值为721.2675mg.kg-1,95%的可信限为595.464~847.071mg.kg-1;白首乌总苷醋酸降解产物的LD50值为984.0087mg.kg-1,95%的可信限为833.8096~1134.2078mg.kg-1。结论白首乌总苷醋酸降解产物的LD50值升高,说明醋酸水解降低了白首乌C21甾总苷的毒性,为进一步研究白首乌C21甾总苷的增效减毒作用有显著意义。     

精制蛇毒酶对小鼠急性毒性研究

目的:观察精制蛇毒酶的急性毒性。方法:采用简化机率法对小鼠尾静脉注射和腹腔注射进行急毒实验,计算半数致死量(LD50)。结果:精制蛇毒酶尾静脉给药的半数致死量(ivLD50)为6.695u﹒kg-1,95%的可信限为6.695±1.498u﹒kg-1;腹腔给药的半数致死量(ipLD50)为4.677u﹒kg-1,95%可信限为4.677±0.793u﹒kg-1。结论:在实验剂量下,精制蛇毒酶低毒、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.     

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.