石榴叶提取物中鞣花酸在大鼠体内药物动力学研究

目的通过大鼠口服石榴叶提取物,研究其中活性成分鞣花酸的药动学特征。方法采用反相HPLC法,紫外检测,应用药动学软件3p87拟合大鼠体内鞣花酸的药动学模型。结果鞣花酸在大鼠体内呈二室模型分布,主要药动学参数为:α=1.07h-1,β=0.12h-1,Ka=5.67h-1,t1/2α=0.65h;t1/2β=5.94h;t1/2Ka=0.12h;K21=0.36h-1;K10=0.35h-1;K12=0.48h-1;AUC=0.85g·h·L-1。结论鞣花酸药动学特征为口服血药浓度低,大部分经胃吸收,达峰时间短,快速吸收、快速分布消除。石榴叶中鞣花酸的吸收大于鞣花酸单体的吸收。     

不同溶媒提取对川芎提取物中阿魏酸药动学的影响

目的考察不同溶媒提取是否对川芎提取物中阿魏酸大鼠体内药动学有影响.方法给大鼠分别灌胃3种不同溶媒的川芎提取物后,用高效液相色谱法测定血浆中阿魏酸的浓度,计算相应的药动学参数.结果3种不同溶媒的川芎提取物大鼠灌胃后阿魏酸的t1/2幔瑃1/2猓琕d/F,CL/F,AUC0-t,Tmax,Cmax存在一定差别,其中乙醇提取物大鼠灌胃后AUC0-t为(2.9±0.4)mg·L-1·h-1,而水提取物和醋酸乙酯提取物大鼠灌胃后AUC0-t分别为(1.3±0.6)mg·L-1·h-1,(1.4±0.4)mg ·L-1·h-1,乙醇提取物阿魏酸的AUC0-t与水和醋酸乙酯的AUC0-t之间差异有显著性.结论不同溶媒提取对川芎提取物中阿魏酸在大鼠体内的药动学有显著影响.     

白芷提取物欧前胡素在大鼠体内的药物动力学

目的通过给予大鼠白芷提取物,探讨其中主要活性成分欧前胡素的药物动力学特征。方法利用RP-HPLC法测定大鼠灌胃白芷提取物后血浆中欧前胡素的血药浓度,用DAS2.0药动学程序求算其药物动力学参数。结果欧前胡素在大鼠体内呈二室模型分布,主要药物动力学参数为:tmax=0.75 h,ρmax=(2.165±0.289)mg.L-1,t1/2=(5.449±2.040)h,AUC0→t=(7.204±3.966)mg.h.L-1,AUC0→∞=(7.512±4.190)mg.h.L-1。结论该法可作为大鼠血浆中欧前胡素的检测及其体内药物动力学研究。     

银杏酮酯及其HP-β-环糊精包合物在大鼠体内的药物动力学

目的建立测定大鼠血浆中槲皮素、山柰素浓度的反相高效液相色谱法,研究银杏酮酯颗粒及其HP-β-环糊精包合物大鼠灌胃后体内药物动力学行为。方法血浆标本水解后,经乙酸乙酯提取,以甲醇-水-磷酸为流动相;12只大鼠随机均分为2组,分别灌胃银杏铜酯颗粒及其包合物后,检测血浆药物浓度。药时曲线采用DAS药代计算程序处理。结果槲皮素在2.6~264.0μg.mL-1,山柰素在1.2~120μg.mL-1与峰面积线性关系良好。结果表明GBE50经包合后,槲皮素主要药动学参数Cmax,tmax,AUC0-t,AUC0-∞分别为(0.219 4±0.034 5)mg.L-1、(4±1)h、(0.872±0.243)h.mg.L-1、(0.843±0.431)h.mg.L-1;参比制剂中槲皮素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为(0.164 6±0.004 1)mg.L-1、(8±3)h、(0.434±0.132)h.mg.L-1、(0.577±0.143)h.mg.L-1。GBE50经包合后山柰素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为(0.016 3±0.003)mg.L-1、(1±0.2)h、(0.077±0.023)h.mg.L-1、(0.09±0.04)h.mg.L-1;参比制剂中山柰素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为(0.015 5±0.002)mg.L-1、(8±3)h、(0.023±0.003 5)h.mg.L-1、(0.026±0.011 2)h.mg.L-1.以槲皮素计,包合物的相对生物利用度为146.10%;以山柰素计,包合物的相对生物利用度为346.15%。结论该法准确,适用于槲皮素和山柰素血浆浓度的测定;制备的银杏酮酯-羟丙基-β-环糊精包合物与银杏铜酯颗粒相比,吸收明显增加。     

强的松对塞克硝唑在大鼠体内的药物动力学行为的影响

目的建立测定大鼠血浆中塞克硝唑的HPLC法,并用于考察联合使用强的松后塞克硝唑在大鼠体内药动学行为的改变。方法 12只健康雄性SD大鼠随机分成2组(分别为单独和联合给药组),采用HPLC法测定血浆中塞克硝唑的浓度。流动相为乙腈-0.02 mol.L-1磷酸二氢钾(体积比为25∶75,pH 3.0),流速为1 mL.min-1,检测波长为320 nm。结果大鼠单独灌胃给予塞克硝唑与联合强的松给药组主要的的药动学参数:ρmax分别为(95.2±3.7)和(97.6±14.9)mg.L-1,tmax分别为(0.67±0.26)和(0.79±0.46)h,t1/2分别为(3.71±0.73)和(4.47±1.68)h,AUC0-t分别为(587±50)和(663±72)mg.h.L-1,AUC0-∞分别为(592±49)和(669±73)mg.h.L-1,均无显著性差异(P>0.05)。结论强的松对塞克硝唑在大鼠体内的药动学行为无显著影响。     

银杏内酯B及银杏内酯提取物大鼠体内药动学比较

目的:研究银杏内酯B、银杏内酯提取物在大鼠体内的药动学。方法:LC-MS测定血浆中银杏内酯B的血药浓度,采用3p87药动学处理软件,计算药动学参数,Cmax、tmax采用实测值。结果:银杏内酯B单体、银杏内酯提取物大鼠口服后的t1/2α分别为(0.18±0.09)、(0.17±0.07)h;t1/2β分别为(2.3±2.0)、(2.3±1.5)h;AUC0-12h分别为(2701±655)、(2889±836)μg.L-1.h;AUC0-∞分别为(2778±680)、(2966±854)μg.L-1.h,银杏内酯提取物中银杏内酯B的生物利用度是单体的1.07倍。结论:银杏内酯B单体、银杏内酯提取物大鼠口服后的药动学参数差异均无统计学意义,银杏内酯提取物中共存成分对银杏内酯B的大鼠体内药动学行为影响无统计学意义。     

盐酸小檗碱单次和多次给药在Beagle犬体内的药动学

目的研究盐酸小檗碱胶囊单次和多次给药后在Beagle犬体内的药动学。方法 6条Beagle犬按150 mg单次和多次口服盐酸小檗碱胶囊,多次给药每天1次,共7 d。采用UPLC-MS/MS色谱法测定犬血浆中盐酸小檗碱的浓度。用DAS 2.0药动学软件处理血药浓度数据。用SPSS统计软件对所得的药动学数据进行显著性差异分析。结果单次给药后主要药动学参数t1/2为(18.85±10.54)h,ρmax为(4.18±2.59)μg.L-1,AUC0-t为(110.04±70.22)μg.h.L-1,AUC0-∞为(121.51±74.19)μg.h.L-1,CL为(1 593.57±745.01)L.h-1,V为(44 509.1±34 995.4)L,tmax为(20.42±22.98)h;多次给药达稳态后主要药动学参数t1/2为(18.53±9.99)h,ρmax为(9.92±7.01)μg.L-1,AUC0-t为(164.51±119.70)μg.h.L-1,AUC0-∞为(172.34±125.03)μg.h.L-1,CL为(1 280.19±709.95)L.h-1,V为(33 655.7±27 632.2)L,tmax为(6.08±4.90)h。结论盐酸小檗碱单次和多次给药后在Beagle犬体内血药浓度均较低,盐酸小檗碱多次给药在Beagle犬体内无明显蓄积现象。     

红花与羟基红花黄色素A大鼠体内药动学的研究

目的:研究红花和羟基红花黄色素A(hydrosafflor yellow A,HSYA)大鼠体内药动学的特征。方法:采用HPLC-UV法测定大鼠血浆中HSYA的血药浓度,应用DAS2.0求得药动学参数。结果:红花和HSYA大鼠体内药动学过程符合二室模型,其药动学参数:Cmax分别为(4.89±0.61)mg/L,(4.61±0.19)mg/L;tmax分别为(0.75±0.00)h,(0.75±0.00)h;AUC0~6分别为(7.32±0.44)mg·h·L-1,(8.68±0.93)mg·h·L-1;t1/2α分别为(0.25±0.08)h,(0.69±0.28)h;t1/2β分别为(1.21±0.36)h,(0.98±0.15)h。结论:红花在大鼠体内吸收比HSYA快,代谢比HSYA慢,表明红花中有其他成分影响HSYA的吸收和代谢。     

口服环孢素的肝移植患者药时曲线监测

目的 :研究口服环孢素 (新山地明 )的肝移植患者的药时曲线。方法 :采用荧光偏振免疫法 (FPIA法 )对 14例肝移植患者口服环孢素A(CsA)后进行了药时曲线监测 ,并计算了其药动学参数 :达到峰值浓度的时间tmax、峰值浓度Cmax、0～ 4h药时曲线下面积AUC0→ 4h、0～ 12h药时曲线下面积AUC0→ 12h。结果 :tmax=2 .2± 0 .6h ,Cmax=12 5 9.8± 4 15 .0 μg·L-1,AUC0→ 4h=32 5 0 .1± 10 34.7μg·h·L-1·h ,AUC0→ 12h=72 16 .5± 2 30 0 .1μg·h·L-1。结论 :口服新山地明的肝移植患者各病例间CsA代谢的个体差异非常大     

硝苯地平缓释片与普通片在健康人体内药动学的比较

目的比较硝苯地平缓释片与硝苯地平普通片在健康人体内药动学。方法 12名男性健康志愿者平均分为2组,分别单剂量口服硝苯地平缓释片与硝苯地平普通片20 mg,用高效液相色谱法检测硝苯地平的血药浓度,并用DAS 2.1软件进行数据处理。结果硝苯地平缓释片与硝苯地平普通片主要药动学参数ρmax分别为(1 247.8±78.4)μg.L-1和(1 896.7±109.2)μg.L-1,tmax分别为(4.6±0.7)h和(2.6±0.9)h,t1/2分别为(8.6±2.8)h和(4.8±1.5)h,AUC0-∞分别为(5 879.3±176.2)μg.h.L-1和(3 724.9±121.3)μg.h.L-1,AUC0-t分别为(4 427.8±131.7)μg.h.L-1和(2 936.5±75.4)μg.h.L-1。结论硝苯地平缓释片的tmax、t1/2长于普通片,AUC0-t、AUC0-∞高于普通片,而ρmax低于普通片,说明硝苯地平缓释片具有良好的缓释效果。     

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.