N-三甲基壳聚糖对更昔洛韦凝胶体外促渗作用的考察

［摘要］目的考察N 三甲基壳聚糖（TMC60）对更昔洛韦的体外促渗作用。方法制备含1%TMC60的更昔洛韦凝胶,用Franz扩散池进行体外促渗作用研究,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值分别为3.822 1,4.098 4,4.205 5及4.356 9 μg•（cm2）-1•h-1。与空白组相比,TMC60有显著的促进更昔洛韦体外经皮渗透作用（P＜0.05）,与同浓度氮酮、CS相比,促渗作用差异无统计学意义（P＞0.05）。结论TMC60可显著促进更昔洛韦的体外经皮渗透。     

壳聚糖对丙酸倍氯米松凝胶体外促透作用的考察

目的:考察不同浓度壳聚糖(CS)对丙酸倍氯米松(BD)凝胶体外透皮速率的影响.方法:分别将0.1%.0.5%,1.0%CS用于BD凝胶中作为吸收促进剂,以泊洛沙姆p407为凝胶基质,并以含1%氮酮的BD凝胶作为阳性对照,不含任何促渗剂的BD凝胶作为阴性对照,采用改良Franz扩散池进行大白鼠离体皮肤渗透实验,RP-HPLC法测定接受液中BD的含量,计算累积透过量Q,得出Q-t回归方程及稳态渗透速率J.结果:不同浓度CS对BD凝胶均有一定的促渗作用,并以1.0%促透效果最好,1.0%CS组和氮酮组的J分别为3.78,3.83(μg·cm-2·h-1),两者差异无统计学意义(P>0.05),而与阴性组相比差异均具有统计学意义(P<0.05),其透皮吸收行为符合一级方程.结论:CS对BD凝胶的体外透皮吸收有较好的促进作用,值得进一步研究.     

透皮促渗剂对醋酸地塞米松壳聚糖凝胶透皮特性的影响

目的观察透皮促渗剂对醋酸地塞米松壳聚糖凝胶透皮特性的影响。方法实验分为无促渗剂组和促渗剂组。无促渗剂组为0.75%药物5%壳聚糖凝胶剂;促渗剂组根据含促渗剂不同又分为月桂氮酮+丙二醇、月桂氮酮、丙二醇+二甲亚砜、二甲亚砜+月桂氮酮组。以无毛大鼠皮肤为渗透屏障,进行体外渗透实验,分析该凝胶稳态透皮速率（Js）和Js提高率。结果无促渗剂组①Js为（3.75±0.56） μg&#8226;（cm2） 1&#8226;h 1。促渗剂组效果明显,其中二甲亚砜+月桂氮酮组②Js为（8.12±0.58） μg&#8226;（cm2） 1&#8226;h 1,月桂氮酮+丙二醇组③Js为（5.41±0.74） μg&#8226;（cm2） 1&#8226;h 1,丙二醇+二甲亚砜组④Js为（4.31±0.42） μg&#8226;（cm2） 1&#8226;h 1,月桂氮酮组⑤Js为（4.35±0.36） μg&#8226;（cm2） 1&#8226;h 1。与①比较,②的Js提高率为2.17%（P＜0.01）,与③④⑤比较,②的Js分别为1.51,1.89,1.87倍（P＜0.05或P＜0.01）。结论混合促渗剂具有比单一促渗剂更好的促渗效果。     

八角茴香挥发油经皮渗透性及对布洛芬透皮吸收的影响

［摘要］目的考察八角茴香挥发油的经皮渗透性及对布洛芬的促透作用,为制备八角茴香挥发油和布洛芬外用制剂及筛选天然透皮促进剂提供参考。方法建立布洛芬及八角茴香挥发油中主成分茴香脑的高效液相色谱（HPLC）测定方法。以体外婴儿皮肤为渗透屏障, Franz扩散池法考察八角茴香挥发油经皮渗透性及对布洛芬透皮吸收的影响。结果0.5%,1.0%,2.0%八角茴香挥发油的透皮速率常数（Jss） 分别为（1.675±0.331）,（4.048±0.579）,（5.352±0.166） μg&#8226;（cm2）-1&#8226;h 1。无八角茴香挥发油与0.5%,1.0%,2.0%八角茴香挥发油对布洛芬透皮吸收的Jss分别为（9.416±1.260）,（7.803±1.128）,（9.495±0.749）,（7.334±0.885） μg&#8226;（cm2）-1&#8226;h 1。结论不同浓度八角油和布洛芬对人皮肤均具有良好的渗透性,且呈浓度依赖性,但八角油对布洛芬未表现出促透作用,甚至抑制布洛芬经皮渗透。     

N-三甲基壳聚糖对雌二醇凝胶透皮促进作用的体外研究

目的:研究季铵化程度为60%的N-三甲基壳聚糖对雌二醇凝胶体外透皮吸收的影响。方法:合成季铵化程度为60%的N-三甲基壳聚糖(TMC60),通过1H-NMR确定其季铵化程度。设立含2%TMC60的雌二醇凝胶为TMC60组,含2%氮酮的雌二醇凝胶为阳性组,无促渗剂的雌二醇凝胶为阴性组。通过体外透皮扩散试验得到各组累积透过量(Q),并求出稳态透皮速率(J)。结果:合成得到的TMC60季铵化程度为67.2%。TMC60组的Q和J显著大于阴性组(P<0.05),但与阳性组比较无显著性差异(P>0.05)。结论:2%TMC60与2%氮酮的促渗效果相似,值得进一步研发。     

当归挥发油对尼莫地平透皮吸收的影响

目的研究当归挥发油对尼莫地平体外经皮渗透的影响。方法以30％乙醇 0.9%氯化钠溶液为接收液,不同浓度的当归挥发油为促渗剂,以预处理的体外兔皮肤作为渗透屏障,Franz扩散池进行体外渗透实验,高效液相色谱法测定尼莫地平的含量。结果不同浓度当归挥发油均能显著提高尼莫地平渗透速率（均P＜0.05）,其中1.0%当归挥发油促渗效果最好,渗透速率为36.63 μg&#8226;（cm2） 1&#8226;h 1,是对照组的3.25倍。结论当归挥发油可以作为尼莫地平经皮吸收制剂的促渗剂。     

N-三甲基壳聚糖对芦荟凝胶透皮吸收促进作用的体外研究

目的：研究季胺化程度为60％的N-三甲基壳聚糖（TMC60）对芦荟凝胶体外透皮吸收的影响。方法：分别制备含2％TMC60的芦荟凝胶（TMC60组）,含2％氮酮的芦荟凝胶（阳性组）,无促渗剂的芦荟凝胶（阴性组）。通过体外透皮扩散实验得到各组累积透过量Q9并求出稳态透皮速率Jo结果：TMC60组和阳性组的Q和J均显著大于阴性组（P〈0．05）;而TMC60组和阳性组相比差异无统计学意义（P〉0．05）。结论：2％TMC60与2％氮酮的体外透皮吸收促进效果相似,值得进一步研发。     

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。     

.舍曲林辅助治疗精神分裂症阴性症状40例

［摘要］目的观察舍曲林对精神分裂症阴性症状的疗效和安全性。方法以阴性症状为主的住院精神分裂症患者80例,随机分为治疗组与对照组,各40例。治疗组：利培酮起始剂量1 mg&#8226;d 1,po,平均（4.5±1.3） mg&#8226;d 1,联合舍曲林50～100 mg&#8226;d 1,平均（66.2±23.7） mg&#8226;d 1,po;对照组：利培酮起始剂量1 mg&#8226;d 1,平均（4.9±1.1） mg&#8226;d 1,po。疗程8周。采用阳性与阴性症状量表（PANSS）、不良反应量表（TESS）评定疗效和不良反应。结果4周末两组PANSS总分、阳性因子分、阴性因子分及8周末两组PANSS总分和各因子分与治疗前比较均差异有显著性或极显著性（P＜0.05或P＜0.01）。8周末治疗组PANSS总分及阴性因子分明显低于对照组（P＜0.05或P＜0.01）。结论舍曲林辅助治疗精神分裂症阴性症状有较好的疗效,且安全性好。     

寡聚精氨酸壳聚糖对替硝唑透皮吸收促进作用的体内外研究

摘 要 目的： 考察寡聚精氨酸壳聚糖（CS-R9）的体内外透皮吸收促进作用。 方法: 以离体小鼠腹部全皮为皮肤屏障,采用Franz扩散池,以替硝唑（TNZ）溶液为阴性对照,氮酮TNZ溶液为阳性对照,考察CS-R9对TNZ溶液的体外透皮促进作用;以大鼠为实验动物,随机分为阴性组、氮酮组及实验组,分别给予TNZ溶液,氮酮TNZ溶液及CS-R9 TNZ溶液,于给药后不同时间点取血0.5 ml,用HPLC法测定其中TNZ的浓度,考察CS-R9对TNZ在体透皮吸收促进作用。结果:体外试验结果表明与阴性对照相比,CS-R9对TNZ具有显著的透皮吸收促进作用（P<0.05）,与同浓度氮酮作用差异无统计学意义（P>0.05）;体内透皮实验也表明CS-R9具有显著透皮吸收促进效果,与同浓度氮酮相比,差异无统计学意义（P>0.05）,且对药物具有一定的缓释作用。结论: CS-R9对TNZ的透皮吸收具有理想的促进作用,值得进一步研究。     

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.