高效液相色谱法测定塞来昔布胶囊中塞来昔布的含量

目的 　建立测定塞来昔布胶囊中塞来昔布含量的反相高效液相色谱法。 方法 　以美国 Dikma公司 Diamonsil TMC1 8反相柱 ( 2 5 0 mm×4.6mm,5 μm)为色谱柱 ,流动相为甲醇 -超纯水 ( 85∶ 15 ,V/V) ,流速为 0 .8m L· min- 1 ,检测波长 2 5 4nm,柱温 40℃ ,进样量为 5 μL。考察了流动相不同配比对塞来昔布色谱行为的影响。 结果 　塞来昔布与胶囊剂辅料及其杂质可完全分离 ;分析方法的定量测定下限为 2 5μg· m L- 1 ,线性范围 :2 5～ 10 0 0 μg·m L- 1 ,回归方程为 C=1.86× 10 - 2 F+1.84× 10 - 1 ,r=0 .999( n=8) ,平均回收率为 98.2 3 %,RSD=0 .47%。 结论 　该方法灵敏、准确、简单、快速、可用于塞来昔布胶囊的含量测定     

HPLC法测定塞来昔布胶囊中有关物质

目的 建立一种有效测定塞来昔布胶囊中有关物质的高效液相色谱法,并进行质量方法学研究.方法 采用Pheny1-2Hypersil柱(250 mm×4.6mm,5μm);流动相为甲醇-0.02 mol/L磷酸二氢钾缓冲液(pH 3.0) (45∶55);柱温为40℃;检测波长为215 nm;体积流量为1.3 mL/min;进样量为80 μL.结果 4-[5-(2-甲基苯基)-3-(三氟甲基)-1H-吡唑-1-基]苯磺酰胺的质量浓度在1.0～3.0 μg/mL具有良好的线性关系(r=0.999 6);检测限(S/N=3)为0.4 ng.结论 本方法简便准确、重现性好,精密度高,可有效地检测塞来昔布胶囊中有关物质,并为塞来昔布的检查和方法学研究提供了依据.     

4种非甾体抗炎药治疗类风湿关节炎的成本-效果分析

目的 :探讨 4种口服非甾体抗炎药治疗类风湿性关节炎 6mo的成本和效果。方法 :4 6 1例病人随机分成 4组 ,双氯芬酸组 131例 ,服用双氯芬酸 75～ 10 0mg·d- 1,萘丁美酮组 131例 ,服用萘丁美酮 10 0 0mg·d- 1,美洛昔康组 14 4例 ,服用美洛昔康 15mg·d- 1,塞来昔布组 5 5例 ,服用塞来昔布 2 0 0mg·d- 1,疗程均为 6mo。运用成本 -效果分析对 4组病人进行分析评价。结果 :双氯芬酸、萘丁美酮、美洛昔康、塞来昔布 4组完成疗程病例数分别为12 5 ,12 7,139和 5 5例。在疗程结束时 ,4组间疗效无显著差异 (P >0 .0 5 ) ,塞来昔布组不良反应率明显低于其他 3组 (P <0 .0 1)。 4组总成本分别为(14 0 0±s 32 6 ) ,(15 31± 36 ) ,(2 0 18± 5 2 7) ,(32 2 5±76 7)元 ;成本 -效果比为 (2 0 4 1± 6 12 ) ,(2 5 6 0±6 81) ,(2 985± 70 6 ) ,(4 6 6 7± 1389)元·例 - 1;经敏感度分析后的成本 -效果比为 (1896± 4 5 5 ) ,(2 36 6±6 38) ,(2 6 6 9± 5 89) ,(3978± 96 3)元·例 - 1。结论 :双氯芬酸为治疗类风湿性关节炎的较佳方案 ,在经济许可的情况下 ,偏重考虑药物安全性 ,塞来昔布也是一个较佳选择。     

环氧酶抑制剂对大鼠血小板聚集的影响

目的：研究环氧酶抑制剂艾瑞昔布、氯吲昔布、美洛昔康、塞来昔布和吲哚美辛对环氧酶-1（COX-1）和环氧酶-2（COX-2）的选择性及对大鼠血小板聚集的影响，探讨环氧酶选择性抑制与血小板聚集之间的关系。方法：利用A23187刺激的小鼠腹腔巨噬细胞模型检测COX-1表达的变化；利用LPS诱导的小鼠腹腔巨噬细胞模型检测COX-2表达的变化；利用花生四烯酸和胶原作为刺激剂诱导血小板聚集模型检测化合物对大鼠血小板聚集的影响。结果：上述化合物对COX-1和COX-2的表达均有明显的抑制作用，其对COX-1和COX-2抑制率IC50的比值分别为：艾瑞昔布IC50 coxl／IC50 cox2为6．7；氯吲昔布IC50 cox-1／IC50cox-2为3．5；美洛昔康抑制IC50cox-1／IC50COX-2为3．0；塞来昔布C50cox-1／IC50cox-2为61．5；吲哚美辛抑制IC50cox-1／IC50COX-2为0．66。艾瑞昔布、氯吲昔布、美洛昔康和吲哚美辛抑制花生四烯酸诱导的大鼠血小板聚集的IC50分别为2．98×10-6 mol／L、1．13×10-5 mol／L、6．80×10-6mol／L和1．82×10-6mol／L；其抑制胶原诱导的大鼠血小板聚集的Ic50分别为2．89×10-6mol／L、3．24×10-6mol／L、5.4×10-8mol／L和1．87×10-7mol／L。塞来昔布在10-5mol／L，浓度时对花生四烯酸和胶原诱导的血小板聚集无明显抑制作用。结论：上述化合物对环氧酶选者性抑制南强到弱的顺序依次为塞来昔布、艾瑞昔布、氯吲昔布、美洛昔康和吲哚美辛。随环氧酶抑制的选择性降低，化合物对血小板聚集制作用逐渐增强。     

一阶导数差示脉冲极谱法用于盐酸丁卡因及其制剂的定量研究

本文研究建立盐酸丁卡因及其制剂的一阶导数差示脉冲极谱法。盐酸丁卡因在水溶液中,于0.060V(vs Ag/Cl)处出现一良好的一阶导数差示脉冲极谱峰,在1.0～6.O×10~(-4)mol/L范围内,药物浓度与其一阶导数差示脉冲极谱峰幅值呈良好的线性关系(P<0.o1,r=0.9968)。检测限为1.O×10~(-8)mol/L。方法简便、快速、灵敏,结果准确.     

电化学发光法测定美洛昔康含量的研究

美洛昔康对Luminol电化学发光有强烈的抑制作用,建立了电化学发光法测定美洛昔康含量的新方法。美洛昔康浓度在2.5×10-7~3.0×10-5mol·L-1范围内与发光减少值呈良好的线性关系。检出限为1.0×10-7mol·L-1。对5.0×10-6mol·L-1美洛昔康平行测定10次,相对标准偏差为4.05%。该法具有简便、快速、灵敏的特点,应用于美洛昔康片的测定,结果满意。     

塞来昔布联合烷二硫氨基甲酸对胃癌细胞KDR和AQP1表达的影响

目的探讨塞来昔布联合烷二硫氨基甲酸(PDTC)对胃癌MGC803细胞株凋亡和KDR、AQP1表达的影响。方法 MGC803细胞培养于RPMI-1640培养液中,实验分为对照组、塞来昔布25μmol.L-1组、PDTC 50μmol.L-1组、塞来昔布25μmol.L-1+PDTC 50μmol.L-1组。药物干预细胞48 h后,采用噻唑蓝(MTT)比色法测定细胞抑制率;采用流式细胞术测定细胞周期分布的变化;用transwell小室法检测药物处理前后细胞侵袭力的变化。采用逆转录聚合酶链反应(RT-PCR)、Western-blot检测KDR、AQP1基因和蛋白的表达情况。结果塞来昔布对MGC803细胞增殖有明显的抑制作用,两制剂联合作用时抑制作用更强(P<0.01)。塞来昔布和PDTC均可诱导细胞凋亡,联合作用后细胞凋亡率更高(P<0.01);联合用药与单独用药相比,可使细胞发生明显的G1期阻滞(P<0.01),进一步下调了KDR、AQP1基因和蛋白的表达(P<0.05)。结论塞来昔布和PDTC联合应用具有协同作用,可进一步抑制细胞的生长和迁移,下调KDR、AQP1基因和蛋白的表达,提示两药联合使用治疗胃癌可能具有很大的潜力。     

西咪替丁的单扫描示波极谱测定法

在 0 .1mol/ L HCl介质中 ,西咪替丁有一个不可逆的吸附还原波 ,峰电位为 - 0 .99V (对 SCE) ,二次微分峰电流与西咪替丁浓度在 2× 10 - 7～ 7× 10 - 6 mol/ L 范围内呈线性关系 ,相关系数 r=0 .998。单扫描示波极谱法方法简便快速 ,测定西咪替丁片剂中西咪替丁含量 ,结果与标示量能很好符合 ,平均回收率为 99.7%。     

一阶导数高速脉冲极谱法用于氯化钠的定量分析

本文研究了一阶导数高速脉冲极谱祛,并将其运用于氯化钠及其制剂的定量分析中。在-0.11V(vs Ag/AgCl)处出现一良好的导数极谱峰,在6.2×10~(-4)～3.1×10~(-3)mol/L范围内,浓度与导数峰电流呈线性关系。检测限为3.1×10~(-7)mol/L。操作简便、快速、灵敏,结果准确。     

高效液相色谱法测定人血浆中帕瑞昔布和伐地昔布的浓度

目的建立高效液相色谱法测定人血浆中前体药物帕瑞昔布及其产物伐地昔布的浓度。方法色谱柱为Diamonsil C18柱(150 mm×4.6 mm,5μm),柱温30℃,流动相为乙腈-水-磷酸(57∶43∶0.01,V/V/V),流速1.0 mL.min-1,检测波长240 nm;内标为塞来昔布。结果帕瑞昔布的线性方程为Y=0.017 8X-0.022 9(r2=0.999 9),线性范围为1～100 mg.L-1。伐地昔布回归方程为Y=0.315 2X-0.005 1,(r2=0.999 8),线性范围为0.05～5 mg.L-1。帕瑞昔布和伐地昔布日内及日间RSD均小于15%,回收率均大于85%。结论本方法灵敏度高、专一性好、操作简单,可同时检测血浆中帕瑞昔布和伐地昔布,能满足药动学研究需要。     

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.     

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.     

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.     

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.