乌芪舒筋通络片中乌头碱限量检测方法研究

目的:建立测定乌芪舒筋通络片中乌头碱限量的方法。方法:采用薄层色谱(TLC)法对制剂中的乌头碱进行鉴定。薄层板为硅胶G薄层板,展开剂为甲苯-乙酸乙酯-三氯甲烷-丙酮-氨水(20∶18∶3∶6∶1,V/V/V/V/V),显色剂为稀碘化铋钾试液和亚硝酸钠乙醇试液。经耐用性和检测限考察,并优选薄层板、温度和湿度。结果:乌头碱的TLC图斑点清晰且阴性对照无干扰。本试验耐用性良好;检测限为0.9μg;可用薄层板为Merck HPTLC预制板、硅胶G薄层板和自制的以羧甲基纤维素钠为黏合剂的硅胶G薄层板;温度为5~16℃,湿度为32%~72%。结论:本方法操作简便、重复性良好,可用于乌芪舒筋通络片中乌头碱限量的测定。     

薄层色谱法检查蚁乌风湿膏中毒性生物碱的限量

目的：建立蚁乌风湿膏中毒性生物碱士的宁、马钱子碱和乌头碱的限量检查方法.方法：采用薄层色谱法,分别采用甲苯-丙酮-乙醇-浓氨试液（4：5：0.6：0.4）、环已烷-乙酸乙酯-二乙胺（5：4：1）为展开剂,稀碘化铋钾试液为显色剂.结果：蚁乌风湿膏中士的宁和乌头碱的检测限分别为0.3,0.6μg.结论：该方法简便,灵敏度高,重复性好,阴性无干扰.可用于蚁乌风湿膏的质量控制.     

液-质联用法同时测定大鼠血浆中的乌头碱、新乌头碱、次乌头碱及其药动学

目的:建立HPLC-MS分析方法同时测定大鼠血浆中的乌头碱、新乌头碱、次乌头碱含量,并用于研究大鼠口服附子煎液后乌头碱、新乌头碱、次乌头碱的药动学。方法:血浆经氨水碱化后用醋酸乙酯进行液-液萃取。色谱柱为Alltima C18柱(250mm×4.6mm,5μm),流动相为甲醇-10mmol.L-1醋酸铵水溶液(75∶25)。质谱检测方式为选择性离子监测,选择监测的离子为m/z646.45(乌头碱),m/z632.38(新乌头碱),m/z615.64(次乌头碱)和m/z336.60(盐酸小檗碱,内标)。结果:血浆中乌头碱在0.05~5μg.L-1、新乌头碱在0.5~50μg.L-1、次乌头碱在2.5~250μg.L-1范围内线性关系良好,定量限为0.05μg.L-1,血浆中的平均提取回收率高于90%,批内和批间精密度均小于15%。结论:本法灵敏、可靠、简便,适用于乌头碱、新乌头碱、次乌头碱的药动学研究。     

高效液相色谱法在康复新胶囊中新乌头碱、次乌头碱和乌头碱含量测定中的应用分析

目的:创建高效液相色谱法并对康复新胶囊中新乌头碱、次乌头碱和乌头碱含量进行测定。方法:在氨水的基础上进行乙醚提取,利用OasisMCX固相萃取柱纯化提取液,分析柱是ZORBAX SB-C8(250mm×4.6mm,5μm),流动相是0.04mol·L-1三乙胺(磷酸调pH=3)-甲醇(50∶50),柱温是40℃,检测波长是235nm。结果:在0.002~1μg的范围里,新乌头碱、次乌头碱、乌头碱的线性关系相对较好,回收率超过90%,RSD在2%以下。结论:高效液相色谱法操作相对简便,准确率高,分离效果好,能有效测定康复新胶囊中新乌头碱、次乌头碱和乌头碱含量。     

复方羊角片中乌头碱的限量检查

目的:对复方羊角片中的乌头碱进行限量检查;方法:采用薄层色谱法对复方羊角片中的制川乌所含的乌头碱进行限量检查,使用硅胶G薄层板,展开剂为:甲苯-醋酸乙酯-二乙胺(14:4:1)。结果:专属性及重现性好,能够很好的控制乌头碱的限量。结论:该方法简便、快捷,专属性及重现性好,结果准确可靠,可用于该品的质量控制。     

伍用刺乌头碱对3-乙酰乌头碱毒性及镇痛作用的影响

刺乌头碱(0.5mg·kg~(-1))对3-乙酰乌头碱(0.07mg·kg~(-1))诱发大鼠心律失常有显著的对抗作用.二者伍用(剂量LA:AA=7:1)对镇痛作用无明显影响.但刺乌头碱可显著提高3-乙酰乌头碱小鼠的LD_(50),从而提高其治疗指数.扩大其安全范围。     

复方软骨素片中乌头碱限量检查方法的探讨

目的:探讨检查复方软骨素片中乌头碱限量的方法.方法:采用薄层色谱法检查,用碱性氧化铝薄层板,以正己烷-醋酸乙酯(1:1)为展开剂,将碘化钾试碘液与碘化铋钾试液等容混合液为显色剂.结果:采用薄层色谱法可以对复方软骨素中的乌头碱限量进行检查.结论:薄层色谱法简单、方便,可用于复方软骨素片的质量控制.     

RP-HPLC同时测定止痛方提取物中6个成分的含量

目的:采用高效液相色谱法同时测定止痛方提取物中芍药苷、原阿片碱、新乌头碱、延胡索乙素、乌头碱、次乌头碱6个成分的含量。方法:采用Venusil XBP-C18(4.6 mm×250 mm,5μm)色谱柱,流动相为甲醇-乙腈-0.1%氨水(磷酸调pH至9.0)梯度洗脱,流速1.0 mL.min-1,检测波长为230 nm(0～12 min,检测芍药苷)、280 nm(12～26 min,检测原阿片碱)、235 nm(26～29 min,检测新乌头碱)、280 nm(29～31 min,检测延胡索乙素)、235 nm(31～50 min,检测乌头碱、次乌头碱),柱温30℃。结果:6个成分的峰面积与浓度的线性关系良好(r>0.9994);加样回收率为96.7%～102.6%。结论:该方法简便、准确,重复性好,为止痛方制剂的质量控制提供依据。     

高效液相色谱法同时测定中药附子中乌头碱、中乌头碱和次乌头碱的含量

目的:探讨中药附子中乌头碱、中乌头碱和次乌头碱的高效液相色谱测定方法.方法:采用HypersilC18(4.6mm×250mm,5.0μm),以甲醇:0.05%磷酸溶液(三乙胺溶液调节pH值6.2)=60:40,检测波长为252nm,柱温为35℃,流速为0.8mL/min.结果:乌头碱回归方程为Y=1.285×103+0.324×102(r=0.9997),在0.261~1.559μg范围内呈较好的线性关系;中乌头碱回归方程为Y=3.354×103+0.015×102(r=0.9996),在0.526~2.031μg范围内线性关系良好;次乌头碱线性回归方程为Y=1.329×103-0.426×102(r=0.9999),在0.152~1.352μg范围内线性关系良好.结论:高效液相色谱法对中药附子中3种有效成分进行测定,方法简单易行,重现性好,精密度高,可作为附子质量控制的方法.     

高效液相色谱法分离测定康复新胶囊中乌头类生物碱含量

目的:建立一种用高效液相色谱法分离测定康复新胶囊中新乌头碱、次乌头碱和乌头碱含量的方法。方法:应用氨水碱化后,乙醚提取,提取液通过Oasis　MCX固相萃取柱对样品进行纯化,以ZORBAX SB-C8柱（250mm×4.6mm,5μm）为分析柱,0.04mol·L-1三乙胺（磷酸调pH=3）-甲醇（50:50）为流动相,检测波长235nm,柱温40℃。结果:新乌头碱、次乌人碱和乌头碱约在0.002～1μg范围内线性关系良好,其回收率>90％,RSD<2％。结论:该方法准确、专属,分离效果好,灵敏度高。     

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.     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.