穿心莲内酯3,19-缩醛（酮）衍生物对小鼠脾淋巴细胞增殖活性的影响*

目的:评价穿心莲内酯及其衍生物对小鼠脾淋巴细胞增殖活性的影响,用于指导以穿心莲内酯为先导化合物的新型免疫调节剂的合成。方法:采用MTT法,在1.56~12.50μmol.L-1定量考察穿心莲内酯及其3,19-缩醛(酮)衍生物对小鼠脾淋巴细胞增殖反应的影响。结果:穿心莲内酯对丝裂原诱导的淋巴细胞增殖活性有显著的抑制作用。通过半合成改造得到的3,19-缩醛(酮)衍生物可使抑制活性显著提高,但是部分衍生物在1.56~6.25μmol.L-1内表现出促进T或/和B淋巴细胞增殖的作用。结论:穿心莲内酯3,19-缩醛(酮)衍生物对穿心莲内酯作为开发免疫调节剂的先导化合物有重要价值和潜力。     

穿心莲内酯衍生物抗肿瘤、解热抗炎构效关系研究进展

目的对近年来穿心莲内酯衍生物抗肿瘤、解热抗炎的构效关系研究进展综述,为穿心莲内酯的进一步研究提供思路。方法对相应文献进行归纳、总结和综述。结果穿心莲内酯及其衍生物发挥抗肿瘤活性的必需基团是完整的α-亚烷基-γ-丁内酯,Δ12,13双键,Δ8,17双键或成环及C14羟基等活性基团;而α-亚烷基-γ-丁内酯环打开与否和抗炎无关,穿心莲内酯及其衍生物的双键位置决定其抗炎作用,具有环内双键的化合物抗炎作用强于具有环外双键的化合物。结论穿心莲内酯衍生物具有良好的开发前景,应加强其衍生物与构效关系的研究。     

固态穿心莲内酯的降解

穿心莲Andrographis paniculata(Burm.f.)Wall.ex Nees.主要活性成分是穿心莲内酯(1)及其衍生物脱氧穿心莲内酯(2)、新穿心莲内酯(3)和14脱氧-11,12-二脱氢穿心莲内酯(4)等三萜内酯。该植物地上部分干粉在干燥环境中贮存一年以上,其总内酯含量减少26％。作者研究了穿心莲内酯在高温条件下的稳定性和可能的主要降解途径。     

连续应用穿心莲内酯致急性肾功能衰竭一例

穿心莲内酯及其衍生物广泛应用于临床，主要用于抗病毒治疗。关于肾损害的不良反应报道较多，该例患者因有既往过敏史而再次应用穿心莲内酯的不同衍生物而致严重的肾功能衰竭。本病例为研究穿心莲内酯的毒性作用提供参考，同时对于临床杜绝使用商品名有典型的警示作用。     

异穿心莲内酯3,19-双酯类衍生物的合成与表征

目的 设计并合成异穿心莲内酯衍生物.方法 以DCC为缩合剂,DMAP为催化剂,合成异穿心莲内酯3,19-双酯衍生物.结果 合成并表征了9个异穿心莲内酯3,19-双酯衍生物及2个异穿心莲内酯19-单酯衍牛物.异穿心莲内酯与羧酸及缩合剂DCC的摩尔比为1.0;2.5;2.5,于室温下反应4～6 h.结论 所合成化合物结构均经1HNMR、MS确证.     

穿心莲内酯脂质体体外细胞毒性实验

穿心莲内酯（andrographolide）是穿心莲的主要有效成分之一，具有抗菌解热、止咳平喘等作用，临床用于治疗上呼吸道炎症和细菌性痢疾，疗效较好，且副作用小。然而，穿心莲内酯难溶于水，口服生物利用度较低，为提高其在水中的溶解度，穿心莲内酯及其衍生物注射液处方中加入了大量的增溶剂，但后者会增加制剂的毒性。     

穿心莲内酯糖苷衍生物的合成

目的:合成穿心莲内酯糖苷衍生物.方法:对穿心莲内酯的羟基进行糖苷化,合成了穿心莲内酯-葡萄糖苷,穿心莲内酯-半乳糖苷,穿心莲内酯-甘露糖苷.结果与结论:目标化合物经IR、HNMR、MS得到结构确证,可能具有更强的抗艾滋病的潜力.     

穿心莲内酯及其衍生物制剂临床作用特点与不良反应评析

目的了解穿心莲内酯及其衍生物制剂临床作用特点的差异性,为临床合理用药提供参考。方法依据4种制剂的说明书并查阅相关文献资料,从其成分、药理作用及适应症、用法用量、使用溶媒、注意事项、配伍禁忌、不良反应等方面进行比较。结果以穿心莲内酯为基本结构的4种制剂临床作用特点及不良反应存在一定差异。结论临床应加深对穿心莲内酯衍生物不同注射剂作用特点及不良反应的认识,合理选择使用不同制剂,保障用药安全。     

穿心莲内酯类化合物的分析研究——Ⅰ.穿心莲内酯(Andrographolide)衍生物的离子对高速液相色谱法分析

本文报道了穿心莲内酪的各种水溶性衍生物,如亚硫酸氢钠加成穿心莲内酯,亚硫酸钠加成穿心莲内酯,穿心莲内酯磺酸钠与三乙酰化穿心莲内酯磺酸钠,及其制剂的离子对高速液相色谱法。以0.08%十六烷基三甲基溴化铵(Cetrimide)为对离子,以异丙醇-正戊醇-水(65:27:7)为流动相,pH3～4,硅胶柱,紫外λ220nm为检测器,可使各种衍生物获得完全分离与分别定量。本法准确度与专属性好,最低检出量为1×10^-5g,选择苦味酸为内标,由数据站系统自动存贮并计算分析结果。     

穿心莲内酯衍生物AL-1合成工艺中杂质的分离与鉴定

目的：分离和分析穿心莲内酯衍生物AL-1合成中的杂质,探讨其来源及成因,并以此指导合成工艺改进。方法：采用色谱法分离和分析AL-1合成中的杂质;MS和1H NMR进行结构确证。结果：杂质分别为二羟基缩丙酮保护的穿心莲内酯脱水物和脱水穿心莲内酯。结论：穿心莲内酯14-位羟基在碱性以及较高温度条件下易脱水生成脱水穿心莲内酯。     

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.