盐酸依匹斯汀离子选择性电极的研制与应用

目的探讨盐酸依匹斯汀离子选择性电极的研制方法及其在含量测定中的应用。方法电极以盐酸依匹斯汀-四苯硼钠为载体、磷酸三丁酯（TBP）为增塑剂。结果线性范围为1．0×10^-2-5．0×10^-6mol／L,检测下限为3．0×10^-6mol／L,回收率为98．8％-101．3％。结论电极法含量测定结果与高效液相色谱法一致,该电极可用于盐酸依匹斯汀片剂的含量测定。     

辛伐他汀联合依替米贝治疗高胆固醇血症及对动脉内膜厚度的影响

目的依替米贝（Ezetimibe）加用他汀类可降低低密度脂蛋白胆固醇（low-density lipoprotein，LDL），但是依替米贝对动脉粥样硬化的效果不清楚。方法随机化对照研究，720例患者分别接受80mg／d辛伐他汀或加用10mg依替米贝，均采用超声波检查颈动脉内膜厚度，主要结局为颈动脉内膜厚度平均值变化。结果辛伐他汀组颈动脉内膜厚度变化为（0．0058±0．0037）mm，辛伐他汀加依替米贝为（0．0111±0．0038）mm（P=0．29）；研究期末LDL胆固醇水平辛伐他汀组为（192．7±60．3）mg／dL（4．98±1．56）mmol／L，辛伐他汀加依替米贝组为（141．3±52．6）mg／dL（3．65±1．36）mmol／L（两组间相差16．5％，P〈0．01）；两组间甘油三酯下降相差6．6％、CRP降低相差25．7％，辛伐他汀加依替米贝组降低更显著（P〈0．01）；两组不良反应相似。结论高胆固醇血症患者联合应用依替米贝和辛伐他汀不能显著改变动脉内膜厚度，但对LDL胆固醇和CRP水平降低显著。     

嗜麦芽窄食单胞菌的耐药性调查

目的了解我院2000-2003年嗜麦芽窄食单胞菌（Xan）的耐药性。方法常规的方法对临床标本进行培养分离，API鉴定，K-B法进行药敏试验（结果参照绿脓假单胞菌的标准），结果统计用WHONET5及SPSS软件。结果Xan对临床常用的11种抗生素的耐药率分别为复方磺胺甲恶唑25．0％-36．0％、替卡西林／棒酸39．7％-69，3％、头孢他啶41．2％-61．3％、头孢哌酮／舒巴坦39．7％-57．3％、环丙沙星39.7％-69．3％、头孢匹美69．1％-82．7％、哌拉西林／三唑巴坦69.1％-85．3％、阿米卡星79．4％-97．1％、头孢哌酮85．3％-91．2％、哌拉西林87．2％-100．0％、氨曲南89．3％-95．6％．4年间，哌拉西林、头孢匹美、复方磺胺甲恶唑、头孢哌酮等4种抗生素的耐药率有显著的差异（P〈0．05），其它7种抗生素无差异（P〉0．05）。结论经验治疗Xan感染可选择复方磺胺甲恶唑、替卡西林／棒酸、头孢他啶。     

高效液相色谱法测定琥珀止痛膏中士的宁含量

目的用高效液相色谱（HPLC）法测定琥珀止痛膏中士的宁含量。方法采用十八烷基硅烷键合硅胶为填充剂的依利特ODS—C18色谱柱（4．6mm×250mm，5μm），流动相为0．01mol／L庚烷磺酸钠与0．02mol／L磷酸二氢钾等量混合溶液（用10％磷酸调节pH值为2．8）-乙腈（81：19），检测波长为254nm。结果士的宁质量浓度在6．07～60．70μg／mL范围内与峰面积线性关系良好（r=0．9999），平均加样回收率为99．80％，RSD为1．8％（n=6）。结论HPLC法快速、简便、准确，可用于测定琥珀止痛膏中士的宁含量。     

依巴斯汀联合甘草锌治疗慢性荨麻疹60例临床疗观察

目的观察依巴斯汀联合甘草锌治疗慢性荨麻疹的临床疗效。方法随机将60例慢性荨麻疹患者分成治疗组（依巴斯汀联合甘草锌）和对照组（甘草锌），治疗组口服依巴斯汀10mg，1次／d，甘草锌5g／包，3次／d，对照组仅口服甘草锌5g／包，3次／d，对比两组治疗后的临床疗效。结果治疗组7d，28d痊愈，显效率分别为66．6％和90．1％，均明显高于对照组33．2％和53．4％（χ^2=6．667，P〈0．01；χ^2=5．963，P〈0．15）。结论依巴斯汀联合甘草锌治疗慢性荨麻疹起效快、疗效确切。     

匹多莫德糖浆在健康人体的药动学和生物等效性评价

目的：研究匹多莫德糖浆的人体相对生物利用度和生物等效性。方法：健康志愿者20名,随机双交叉单剂量口服匹多莫德糖浆（受试制剂）和溶液（参比制剂）,剂量分别为20ml（800mg）和14ml（800mg）,采用HPLC法测定血浆中匹多莫德的浓度,用DAS2．1药动学程序计算药动学参数和生物利用度,并进行生物等效性评价。结果：单剂量口服匹多莫德受试和参比制剂后,血浆匹多莫德的Cmax分别为（4．45±1．80）μg·ml^-1和（5．17±1．57）Hg·ml^-1,tmax分别为（2．28±0．550）h和（2．18±0．61）h,t1／2分别为（2．27±1．07）h和（1．98±0．77）h,AUC0-14分别为（21．77±6．48）ng·h·ml^-1和（21．13±5．30）μg.h.ml^-1,AUC0-∞分别为（22．28±6．48）μg·h·ml^-1和（21．564±5．36）μg·h·ml^-1。AUC0-14、AUC0→∞和Cmax的90％可信区间分别为89．2％-116．4％,89．8％-116．9％和74．8％～94．2％。受试制剂的相对生物利用度R0-14和R0-∞分别为（107．69±37．25）％和（108．20±37．13）％。结论：匹多莫德受试制剂和参比制剂具有生物等效性。     

依普利酮原料及其制剂的含量测定方法改进

目的建立HPLC测定依普利酮原料及其片剂、胶囊含量的方法,为标准改进提供参考。方法采用Shim—packVP—ODS柱（4．6mm×150mm,5μm）,以水甲醇-乙腈-三乙胺（50：25：25：0．1）（用冰醋酸调节pH值为5．5）为流动相,检测波长为240nm,流速为1．0mL·min^-1。结果依普利酮在10．10～151．47μg·mL^-1范围内与峰面积呈良好的线性关系（r=0．9999）,依普利酮胶囊的平均回收率为100．23％,RSD为0．95％;依普利酮片的平均回收率为100．77％,RSD为0．76％。三批原料的含量测定结果分别是：99．9Yo、99．8％和99．9％;三批片剂的含量测定结果分别是：96．5％、96．89／6和97．4％;三批胶囊的含量测定结果分别是：97．6％、98．3％和98．2％。结论该方法经方法学验证可用于依普利酮原料、片剂、胶囊的质量控制。     

依折麦布片HPLC含量测定方法学研究

目的建立依折麦布含量测定方法。方法采用高效液相色谱祛,以Agilent SB-C18（5μm,150mm×4．6mm）为色谱柱,以0．05mol／L磷酸二氢钾溶液-乙腈-四氢呋喃（65：25：10）为流动相;检测波长为232nm,柱温为25℃,流速为1．0mL／min。结果含量测定方法学研究表明,该方法专属性好;依折麦布在40．23-402．30μg／mL的浓度范围内与其峰响应值呈良好的线性关系,平均回收率为98．8％（RSD=0.3％）。结论本方法测定结果准确,精密度高,耐用性良好,可以作为依折麦布的含量测定方法。     

RP—HPLC法测定瘫痿胶囊中马钱子碱和士的宁的含量

目的建立以反相高效液相色谱法测定瘫痿胶囊中马钱子碱和士的宁含量的方法。方法色谱柱为依利特C18（4．6×150mm，5μm），流动相为：0．01mol／L庚烷磺酸钠与0．02mol／L磷酸二氢钾等量混合溶液（用10％磷酸调节pH值2．8）-乙睛（79：21），流速：1．0ml／min，检测波长：260mm，柱温：30℃。结果马钱子碱进样量在0．1296～1．9440μg（r=0．99996）范围内，士的宁的进样量在0．1338—2．0070μg（r=0．99993）的范围内与峰面积积分值呈良好的线性关系。平均加样回收率马钱子碱为99．91％，RSD=1．95％，（n=6）；士的宁为99．60％，RSD=1．48％，（n=6）。结论本方法简便、快速、准确、重现性好，可用于瘫痿胶囊的质量控制。     

顶空气相色谱法测定匹伐他汀钙中有机溶剂残留量

目的建立以顶空进样测定匹伐他汀钙原料药中有机溶刑残留量的方法。方法以N，N-二甲基甲酰胺为溶剂，平衡温度为90℃，平衡时间为30min。采用DM-624毛细管柱（内涂6％氰丙基苯基硅氧烷和94％聚甲基硅氧烷），检测器为FID，载气为№，流速为5mL／min，分流比为3：1，顶空进样量为1．0mL。结果二氯甲烷、四氢呋喃、乙醇、正己烷、甲苯、环己烷和乙腈的质量浓度线性范围分别是12．2-304．8μg／mL，14．4—359．6μg／mL，101．1—2528μg／mL，5．8～145μg／mL，17．9—446．5μg／mL，77．8—1945μg／mL，8．1—203．3μg／mL；平均回收率分另4为98．0％，99．0％，98．2％，99．2％，98．5％。99．6％，97．5％。结论顶空气相色谱法简单，灵敏度高，测定结果准确，可用于匹伐他汀钙有机溶剂残留量的测定。     

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.