免疫磁性制剂的研究

磁性药物制剂是将药物和铁磁性物质共包于或共分散于载体中应用于体内,然后利用体外磁场效应引导药物在体内移动并定位集中的靶向给药制剂。这类制剂包括:1 免疫磁性微球(immunomanetic microsphere) 制备此微球一般可分2步:①制成含磁性材料的微球;②在微球表面引入活性基因如OH,COOH,NH_2等,再通过载体表面偶联反应将抗体、酶或免疫毒素结合到载体上,     

天然高分子磁微球作为靶向制剂的研究进展

磁性微球作为靶向药物载体有利于提高药物疗效，降低药物的毒副作用，为化疗药物的临床应用开辟了新途径。文章着重综述和评价了以天然高分子材料为载体的磁性微球的制备和应用，并对相关研究工作中存在的问题提出了看法。     

多柔比星磁性葡聚糖微球的制备及特性检测

目的:制备多柔比星磁性葡聚糖微球并检测其特性。方法:采用吸附法制备多柔比星磁性葡聚糖微球。高倍显微镜观察微球粒径大小及形态,紫外分光光度法检测微球中多柔比星的含量,测定微球磁吸附率,计算求和值 S,确定最佳投料比(药物:载体),绘制药物微球体外释放曲线。结果:制备的多柔比星磁性葡聚糖微球最佳投料比为1:15,磁吸附率为100%。微球外形圆整,分散性好。多柔比星30 min 释放28%;60min 释放45%;6h 释放65%。结论:制备的多柔比星磁性葡聚糖微球缓释性好,磁响应性强,可作为一种治疗顽固性疼痛的靶向神经损毁剂。     

抗癌药物白蛋白微球的研究进展

为提高抗癌药物对癌细胞或组织的靶向性,增强疗效,降低其全身毒副作用,以不同材料作载体的抗癌药物微球相继研制成功:不可生物降解的乙基纤维素微球,可生物降解的白蛋白微球、淀粉微球、明胶微球、聚乳酸微球,以及近年来问世的磁性微球、毫微球等。白蛋白微球以其良好的生物相容性和可降解性被广泛用于抗癌药靶向给药系统。 白蛋白微球最初用于动物及人的肺部扫描和循环系统研究,自1974年首次作为抗癌药物载体以来,相继用作诊断试剂及靶向给药、化学栓塞治疗的载体。1 抗癌药物动脉栓塞白蛋白微球 肿瘤动脉栓塞疗法是将抗癌药物制剂选择性注入支配     

磁性微球的磁响应性及狗肾动脉栓塞实验研究

研究了磁性明胶微球(MG-ms)的磁响应性及狗肾动脉栓塞效果。磁响应性实验表明,介质流速越慢,磁场强度越大,磁性微球中磁铁粒子含量越高,越容易定位磁性微球。狗肾动脉灌注10～30um磁性微球,血管造影和病理切片结果表明:磁性微球在外磁场作用下可以进一步栓塞至肾小球、肾脏的微细动脉,而且栓塞均匀、完全,而不加磁场时栓塞不完全。这些结果提示磁性明胶微球可以作为治疗肾癌的栓塞剂,将有利于增强化疗效果、减少毒副反应。     

5—氟脲嘧啶磁性微球的制备及其性能的探讨

将5—氟脲嘧啶，牛血清白蛋白和磁性液体混合乳化，在不同温度下固化，然后制成粒径l～2μm 的注射用磁性白蛋白微球(FMAM)．在体37℃的吐温80的生理盐水中。用各种不同固化温度的磁性微球进行释 放试验，结果表明：微球制备的固化温度越高，微球药物释放越缓慢。对磁性液体配比不同的微球药释试验结果 表明，磁性液体配比越高其释药越缓慢。另外，还对磁性徽球在不同磁感应强度下的磁应答性以及在小白鼠体内皮 下组织的分布情况作了初步研究.     

低剂量阿霉素磁性微球的体内动力学

作者将低剂量阿霉素(0.05mg/kg)包封在磁性微球中,以100倍高剂量的游离型阿霉素静脉注射(5mg/kg)作对照,用小白鼠尾为靶部位进行体内动力学研究。实验表明,在给药后60分钟,低剂量阿霉素磁性微球在靶部位保留时间约为游离型阿霉素二倍的浓度。以~(125)I标记微球,测定载体的体内分布。将鼠尾分为四段,第三段为靶部位暴露于强度为8000奥斯特(Oe)的磁场、梯度±4000 Oe。在鼠腹侧尾动脉注射微球5～60分钟内,肝、肺、脾仅有少量分布;心、肾和鼠尾1,     

RP-HPLC法测定5-Fu磁性微球及小鼠各组织中5-Fu的含量

目的:以反相高效液相色谱法测定5-氟尿嘧啶(5-Fu)磁性微球及小鼠各组织中5-Fu的含量,并评价5-Fu磁性微球在小鼠体内的靶向性。方法:15只小鼠尾静脉注射5-Fu及其磁性微球,采用0.5%胃蛋白酶消解磁性微球后经乙酸乙酯2次萃取后以反相高效液相色谱法测定心、肝、肾、脾、肺、脑和肌肉等组织匀浆中5-Fu含量。结果:组织匀浆中5-Fu检测浓度在0.1～25mg·L-1范围内线性关系良好,最低检测浓度为0.1mg·L-1。与注射单一5-Fu对照品比较,小鼠静脉注射5-Fu磁性微球后在肝脏分布明显增加(P<0.05),加入磁性支架和体表磁场的肌肉组织中可见5-Fu分布。结论:本方法适用于测定磁性微球及小鼠各组织中5-Fu的含量;5-Fu磁性微球具有肝靶向性和磁靶向性。     

磁性壳聚糖微球制备及生物相容性的研究

目的:制备5-氟尿嘧啶磁性壳聚糖微球并评价空载磁性壳聚糖微球的生物相容性。方法:采用乳化交联法制备5-氟尿嘧啶磁性壳聚糖微球并优化制备工艺,采用扫描电镜和振动样品磁强计(VSM)对微球进行表征;四噻唑蓝法观察细胞增殖情况,评估磁性壳聚糖微球的体外细胞毒性;溶血实验和血常规检查评估磁性壳聚糖微球的血液相容性;植埋实验评估磁性壳聚糖微球的组织相容性。结果:经过优化后的5-氟尿嘧啶磁性壳聚糖微球包封率和载药量分别为70.2%和12.3%,Z-均粒径为1 479.6 nm,饱和磁化度为4.79 emu.g-1,微球形态良好、均匀圆整;自制空载磁性壳聚糖微球体外细胞相容性符合要求,显示出良好的血液相容性和体内组织相容性。结论:优化了5-氟尿嘧啶磁性壳聚糖微球的制备工艺,制备的空载磁性壳聚糖微球具有很好的生物相容性。     

HPLC法测定磁性微球及大鼠肝组织中的平阳霉素

目的 :建立磁性微球及鼠肝组织中平阳霉素的检测方法 ,评价磁性微球的靶向性。方法 :采用RP -HPLC法 ,紫外检测 ,内标法定量 ,平阳霉素磁性微球采用 pH =4的胃蛋白酶消化后过滤稀释测定 ,鼠肝组织匀浆后离心取上清液用三氯醋酸沉淀蛋白后直接进样分析。结果 :测定样品在 10～ 5 0 μg·mL-1范围内线性关系良好 ,回收率和精密度均较满意。结论 :用本法测定磁性微球及鼠肝组织中平阳霉素 ,可用于研究磁性微球中平阳霉素的含量及组织中分布情况 ,考察磁性微球的靶向性。     

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.