盐酸奥丹西酮离子导入的研究(英)

本文研究了奥丹西酮在不同电流密度下经小鼠全皮的渗透动力学。当电流密度从0.05mA．cm-2升高到0.3mA．cm-2时，药物的稳态流量从30．29μg．cm-2.h-1增加到160.70μg．cm-2.h-1。研究中药物稳态流量和应用电流之间不严格呈线性关系。铂在供药池中作阳极时，可导致药物溶液变色；而应用银电极代替铂电极，则可以避免此问题的出现。应用铂电极时，供药池和接受池中均发现有pH变化。文章对以上问题以及解决的方法进行了讨论。     

盐酸特拉唑嗪贴剂的制备及质量控制

目的：制备盐酸特唑嗪贴剂，研究其耐热，耐寒性，刺激性及透皮吸收性能，方法：以PVA制备盐酸特拉唑嗪贴剂，小鼠皮为模型皮肤，采用Franz扩散池分别进行药物经皮释放试验和渗透试验，并测定了人体透皮速率。结果：盐酸特拉唑嗪贴剂耐热和耐寒性质良好。对皮肤无刺激性。体外释放速率为13．52ug.cm^-2.h^-1，体外透皮速率为11．87ug.cm^-2.h^-1，人体平均透平速率为11．25ug.cm^-2.h^-1，结论：盐酸特拉唑嗪贴剂是一种有效的控释型外用制剂。     

桉油对丙酸氮倍他索乳膏经皮渗透和吸收的作用

目的：考察促进剂桉油对丙酸氯倍他索（CBT）乳膏经皮渗透的促进作用,通过比较透过量和皮层中量,分析在该制剂中是否透合使用桉油,方法：采用直立式扩散池,考察了桉油在0．5％,1．0％,5．0％浓度下0．05％CBT乳膏经皮渗透2,4,6,8,10,24h后单位面积累积透过量Q(ug.cm^-2)和稳态透皮流量J（ug.cm^-2.h^-1);HPLC法测定经皮渗透24h后每克皮肤组织中CBT的量D（ug.g^-1),结果：4种浓度的桉油均显著促进CBT乳膏透皮吸收（P＜0．01）,其J值约是对照组的3－5倍（P＜0．01）,随浓度增加,陂层量D并不随之相应增加,结论：桉油可加快CBT经皮渗透速度,也能增加皮层中CBT量,但有饱和性,建议CBT 乳膏膏以少加（＜50％）或不加桉油为好。     

反相高效液相色谱法测定兔眼玻璃体内吲哚美辛浓度及药物动力学研究

目的测定兔眼玻璃体内吲哚关辛（IN）浓度,研究其药物动力学特征并探讨给药方案。方法50只实验兔随机分为10组,每组5只10眼。除空白组外,其余各组每眼给予浓度为6mg·mL^-1IN溶液0．2mL,分别于注药后0．5、1、2、4、8、12、24、48、72h各处死1组兔子,取玻璃体样本,用反相高效液相色谱法（RP—HPLC）测定玻璃体腔内IN质量浓度。用DAS软件计算主要的药物动力学参数。结果吲哚美辛眼玻璃体内的消除半衰期为6．93h、药时曲线下面积为127．2μg·h^-1·mL^-1、清除率为0．04μg·h^-1结论兔眼玻璃体内吲哚美辛质量浓度变化符合一室模型,若按t1／2给药（τ=t1/2）则3～4次·d^-1的给药方案可达到稳态浓度（Css）。     

N-三甲基壳聚糖对丙酸倍氯米松凝胶体外促透作用的考察

目的：考察N-三甲基壳聚糖（TMC60）对丙酸倍氯米松（BM）的体外促透作用。方法：制备含1％TMC60的BM凝胶,用Frartz扩散池进行体外促透作用研究,以稳态透皮速率J为指标,与同浓度的氮酮、壳聚糖（CS）进行比较。结果：空白组、氮酮组、TMC60组及CS组的J分别为3．8221,4．0984,4．2055和4．3569ug·cm^-2·h^-1。与空白组相比,TMC60有显著的促进BM体外透皮扩散作用（P〈0．05）;而与同浓度氮酮、CS相比,促透作用无显著性差异（P〉0．05）。结论：TMC60可显著促进BM的体外透皮扩散。     

沙丁胺醇经皮渗透性实验研究

本采用反相高教液相色谱法测定了沙丁胺醇饱和水溶液对兔皮和小鼠皮的体外经皮渗透速率．结果表明．沙丁胺醇有较好的经皮渗透性．对兔皮和小鼠皮的渗透速率分别为52.09±9．54μg·cm^-2·h^-1和130．36±28.21μg·cm^-2·h^-1.     

大鼠静注苯妥英钠的毒代动力学研究

目的：探讨苯妥英钠（DPH—Na）在大鼠血液的毒代动力学规律及组织分布。方法：大鼠静注中毒剂量DPH-Na后采集血液及组织样品,HPLC法测定其血浆及组织中药物浓度,分别用隔室模型拟合和米曼氏方程计算毒代动力学参数,并比较各组织中药物浓度。结果：DPH-Na静注中毒剂量后,在大鼠体内符合二室模型过程,主要毒代动力学参数：Cmax=（61．31±7．09）ug·ml^-1,t1／2a：（0．18±0．08）h,t1／2 B：（2．60±0．52）h,AUC=（147．22±29．16）（ug·ml^-1）·h,CL=（0．15±0．02）L·h^-1。按米曼氏方程解析所得主要毒代动力学参数：Vm=（10．42±5．33）ug·ml^-1·h^-1,Km=（66．65±13．71）ug·ml^-1,其余毒代动力学参数与二室模型拟合结果无明显差异（P〉0．05）。DPH-Na在各组织中的浓度顺序依次为：肺〉肾〉肝〉心〉脑。结论：DPH-Na在大鼠体内的毒代动力学与药物动力学规律有差异,其中毒后在体内消除减慢,血液及组织中可能大量蓄积。     

阿奇霉素分散片药物动力学与生物利用度研究

目的 研究阿奇霉素分散片健康人体的药物动力学与生物等效性。方法高效液相色谱．质谱法（LC-MS）测定20名男性健康志愿者随机交叉口服阿奇霉素分散片受试制剂和参比制剂的药时数值。以DAS2．0软件计算其药动学参数,考察其生物等效性。结果受试制剂和参比制剂的药动学参数：tmax分别为（2．1±0．8）h和（3．1±2．2）h;Cmax分别为（433．5±138．1）μg/L和（425、7±184．3）μg／L;AUC0-120h分别为（4231±1198）μg·L^-1·h^-1和（3881±1154）μg·L^-1·h^-1;AUC0～∞分别为（460911207）μg·L^-1·h^-1和（4287±1268）μg·L^-1·h^-1。以AUC0-120h计算,受试阿奇霉素分散片和参比阿奇霉素分散片比较的人体相对生物利用度为（119．6±52．9）％。结论两种不同厂家的阿奇霉素分散片具有生物等效性。     

褪黑激素皮肤渗透性的研究(英)

本文考察了渗透促进剂Azone（AZ）、油酸（OA）、丙二醇（PG）等和离子导入法（Ag／AgCl或Pt电极,电流密度0.19mA／cm2,频率2000Hz,占／空比1：1）对褪黑激素（MT）皮肤渗透性的影响。MT能透过小鼠全皮,其稳态流量和渗透系数分别为1622×10-3μg／cm2．s和0.8888×10-6cm／s：100％AZ、5％AZ／PG和10％OA／PG处理皮肤后,MT的稳态流量分别是未处理组的7.61、7.03和2.98倍;MT作为非离子性药物,离子导入对其也有促渗作用,离子导入处理组的稳态流量是未处理组的2.19倍。结果表明渗透促进剂（AZ、OA）、离子导入法均能增加MT的经皮渗透。     

探针药物法测定大黄对大鼠肝细胞色素CYP2E1酶的影响

目的用探针药物法测定大黄对大鼠肝细胞色素CYP2E1酶的影响。方法将SD舍大鼠随机分组,给药组予大黄灌胃,以生理盐水组为空白对照,尾静脉给予CYP2E1探针药物氯唑沙宗,HPLC法检测体内药动学参数来评价各组的CYP2E1酶活性。结果氯唑沙宗代谢符合二室模型,给药组t1/2β（1．18±0．28）h、AUC（20．09±12．11）mg·h·L^-1、V（c）（0．30±0．21）L、CL（s）（0．94＋0．59）L·h^-1,对照组t1/2β（1．49±0．14）h、AUC（38．87±8．35）mg·h·L^-1、V（c）（0．21±0．06）L、CL（s）（0．12±0．02）L·h^-1.结论大黄对大鼠肝细胞色素CYP2E1有诱导作用。     

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.