泰山紫草与新疆紫草的HPLC指纹图谱对比研究

目的 对比研究泰山紫草和新疆紫草指纹图谱及其主要成分含量,评价泰山紫草的药用价值。方法 采用HPLC,色谱柱为Symmetry C₁₈色谱柱（4.6 mm×250 mm,5 μm）,流动相为乙腈-水（70∶30）,流速为1.0 mL·min^-1,柱温为30℃,检测波长为516 nm。应用中药色谱指纹图谱相似度评价系统（2012年版）软件,建立泰山紫草、新疆紫草指纹图谱。结果 建立了泰山紫草、新疆紫草指纹图谱的共有模式,以新疆紫草对照图谱作为参照图谱,进行峰匹配,对比计算泰山紫草指纹图谱的相似度为0.798,泰山紫草中含有萘醌类有效成分,但含量与新疆紫草中存在差异。结论 泰山紫草具有一定的药用价值,但不可完全替代新疆紫草使用。     

党参生品及不同米炒党参UPLC指纹图谱比较研究

目的 比较小米和大米炒制党参Codonopsis Radix前后的指纹图谱差异。方法 采用超高效液相色谱（UPLC）法,色谱柱为Agilent Poroshell SB-C₁₈,流动相为乙腈-0.15%冰醋酸水（梯度洗脱）,体积流量为0.3 mL/min,检测波长为267 nm,柱温为30℃,进样量为1 μL。以党参炔苷为参照,建立生党参、小米炒党参、大米炒党参（各9批）的UPLC指纹图谱;运用《中药指纹图谱相似度评价系统（2012版）》进行相似度评价及共有峰指认;运用SPSS 20.0软件进行聚类分析;使用数据统计软件SSPS 20.0与SIMCA 14.1进行主成分分析。UPLC法检测大米炒党参、小米炒党参、生党参各9批饮片中5-羟甲基糠醛（5-HMF）和党参炔苷含量。结果 9批党参生品的UPLC指纹图谱有6个共有峰,小米炒党参和大米炒党参分别均有10个共有峰,相似度均大于0.90;指认了5-HMF、党参炔苷2个共有峰,党参“米”炒后UPLC指纹图谱共有峰特征明显,小米炒党参和大米炒党参的UPLC指纹图谱未见明显差异。聚类分析和主成分分析结果一致,9批党参生品聚为一类,而小米炒党参和大米炒党参聚为另一类。与生党参比较,大米炒党参和小米炒党参中5-HMF含量均显著升高（P<0.01）,3种饮片党参炔苷含量无明显差异。结论 成功建立了党参生品及小米炒党参、大米炒党参的UPLC指纹图谱,不同炮制辅料对米炒党参中化学成分的影响趋势相同,但程度不同。     

注射用五味子提取物指纹图谱研究

目的 采用高效液相色谱法建立注射用五味子提取物指纹图谱,并对2015—2016年制备的40批注射用五味子提取物进行指纹图谱相似度分析。方法 试验考察了不同流动相组成和浓度、不同检测波长、不同洗脱方法、不同品牌C₁₈色谱柱（250 mm×4.6 mm,5 μm）、不同流速、不同柱温等条件下供试品溶液的色谱行为,利用中药色谱指纹图谱相似度评价系统对试验所得色谱图进行相似度分析。结果 确定了高效液相色谱检测条件,建立了20批注射用五味子提取物的对照指纹图谱（相似度不低于0.991）,确定了12个共有峰,并对5个共有峰进行了指认,其余20批供试品与对照图谱的相似度均值为0.994。结论 本试验建立的注射用五味子提取物指纹图谱可以为其质量控制提供科学的依据,为完善注射用益气复脉（冻干）质量标准提供数据支持。     

鼻渊净胶囊的HPLC指纹图谱研究

目的 建立鼻渊净胶囊的高效液相色谱（HPLC）指纹图谱。方法 采用Agilent SB-C₁₈（4.6 mm×250 mm,5 μm）色谱柱,乙腈-水为流动相、以1.0 ml/min流速行梯度洗脱,检测波长210 nm,柱温30 ℃,洗脱时间为80 min。采用中药色谱指纹图谱相似度评价系统（2004A版）对检测出色谱进行指纹图谱相似度评价。结果 建立了鼻渊净胶囊的HPLC指纹图谱,确定了20个共有峰,15个峰归属到各药材,其中5个峰确认了化学成分;10批样品的指纹图谱的整体相似度与对照图谱比较,均在90%以上。结论 所建立的鼻渊净胶囊指纹图谱有助于从整体上控制该制剂的质量。     

肾康注射液指纹图谱的研究

目的 建立肾康注射液的超高效液相色谱（UPLC）指纹图谱,并对肾康注射液指纹图谱共有峰进行鉴定。方法 采用超高效液相色谱条件法,色谱柱ACQUITY UPLC^® CSH-C₁₈（2.1mm×100mm,1.7μm）,甲醇（A）-0.1%甲酸溶液（B）二元梯度洗脱,流速0.4 ml/min,检测波长280 nm,进样量2 μl,柱温30℃,使用飞行时间质谱仪,负离子模式扫描。结果 建立了肾康注射液UPLC指纹图谱,采用UPLC/ESI-Q-TOF MS技术共鉴定了26个共有峰。采用《中药指纹图谱相似度评价系统（2012.130723版）》评价了20批肾康注射液,指纹图谱相似度均大于0.90。结论 本方法所建立的肾康注射液指纹图谱灵敏度高,稳定可靠,为肾康注射液的质量控制提供了科学依据。     

知柏地黄丸的UPLC指纹图谱研究

目的 建立知柏地黄丸UPLC指纹图谱的研究方法。方法 采用Waters Acquity BEH C₁₈色谱柱（2.1 mm×100 mm,1.7 μm）,流动相为乙腈-0.1%磷酸,梯度洗脱,检测波长236 nm,流速0.4 mL·min^-1,柱温40℃,以丹皮酚作为参照物。结果 在12 min内完成指纹图谱分析,标出12个共有峰,对6个色谱峰进行了归属,并进行了相似度评价。结论 UPLC简便可行,建立的指纹图谱可用于知柏地黄丸的质量控制。     

基于HPLC-ELSD指纹图谱与化学计量学相结合的舒眠胶囊质量评价

目的 建立舒眠胶囊HPLC-ELSD指纹图谱与化学计量学相结合，全面、系统评价舒眠胶囊质量的方法。方法 采用ACE Excel AR C₁₈色谱柱（4.6 mm×250 mm，5.0 μm），流动相为乙腈-水，梯度洗脱，柱温30℃，流速为1.0 mL·min^-1，ELSD漂移管温度50℃，N₂流速为3.0 mL·min^-1。用HPLC-ELSD对15批次舒眠胶囊进行分析，建立指纹图谱共有模式，采用聚类分析（cluster analysis，CA）、主成分分析（principal component analysis，PCA）等化学计量学方法进行区分与比较，寻找导致不同批次间差异的主要标志性成分。结果 共确定了16个共有峰，归属了10个共有峰的药材来源，通过对照品比对指认了4个共有峰归属，分别为柴胡皂苷a、芍药内酯苷、芍药苷、槲皮苷，样品相似度均>0.90，CA将样品分为3类，PCA筛选出不同批次间差异的主要标记物，分别为3（芍药苷），14，15号峰。结论 本研究建立的HPLC-ELSD指纹图谱与HPLC-DAD指纹图谱相结合能对舒眠胶囊产品一致性、稳定性进行全面有效评价，可用于舒眠胶囊的质量综合评价。     

基于指纹图谱的银翘解毒颗粒质量评价

目的 采用HPLC建立银翘解毒颗粒指纹图谱,整体评价该制剂质量。方法 采用Waters CORTECS^TM C₁₈色谱柱（4.6 mm×150 mm,2.7 μm）,以乙腈为流动相A,0.1%甲酸为流动相B,梯度洗脱,流速为0.5 mL·min^-1,柱温为25℃,检测波长为245 nm;采用LC-MS对银翘解毒颗粒物质基础进行解析并对色谱峰进行归属;运用中药色谱指纹图谱相似度评价系统软件,对28家生产企业的28批样品进行相似度评价。结果 建立了银翘解毒颗粒的HPLC指纹图谱;检测到34个成分,鉴定了其中30个成分,特征峰分别归属于金银花、连翘、牛蒡子、薄荷、荆芥、甘草和淡豆豉7味药;28批样品的相似度值为0.77~0.99。结论 相似度评价结果发现个别企业存在低劣饮片投料或工艺过程控制不严等违规生产现象。建立的指纹图谱方法便捷、特征性强、重复性好,为综合评价和控制产品质量提供了依据。     

前胡香豆素类成分HPLC指纹图谱研究

目的 建立前胡香豆素类成分的HPLC指纹图谱，为科学评价其质量提供可靠方法。方法 采用Ecosil-C₁₈色谱柱（4.6 mm×250 mm，5 μm），以甲醇-水（68：32）为流动相，分析时间50 min，流速1.0 mL·min^-1，柱温40℃，检测波长323 nm；采用LC-MS对前胡香豆素类成分进行解析，并对特征峰进行归属；运用中药色谱指纹图谱相似度评价系统软件，对18批前胡样品和4批混淆品进行相似度评价。结果 以白花前胡甲素和白花前胡乙素为参照物，建立了以8个共有峰为指标成分的前胡药材指纹图谱，通过LC-MS定性分析结合对照品比对，推测8个共有峰为前胡香豆素D、前胡香豆素E、peucedanumarin Ⅱ、白花前胡甲素、peucedanumarin Ⅰ、白花前胡乙素、白花前胡素E及其同分异构体，并且以相似度为0.9能很好地区分前胡正品和混淆品。结论 该方法简单、重复性良好，可为前胡药材的质量评价提供有效鉴别方法。     

经典名方泽泻汤UPLC指纹图谱的建立

目的 建立泽泻汤的UPLC指纹图谱。方法 采用ACQUITYUPLC^ÒBEH C₁₈色谱柱（2.1 mm×50 mm，1.7 μm），以乙腈（A）-水（B）作为流动相进行梯度洗脱，柱温35℃，流速0.3 mL·min^-1，全波长扫描，以泽泻醇B为参照峰，分析15批次泽泻汤的UPLC指纹图谱，并使用中药色谱指纹图谱相似度评价系统结合主成分分析、正交偏最小二乘法判别分析（PLS-DA）评价泽泻汤的指纹图谱。结果 在泽泻汤指纹图谱中共标定23个共有峰，其中15个化合物峰来自泽泻，8个化合物峰来自白术，指认了白术内酯Ⅰ、白术内酯Ⅱ、白术内酯Ⅲ、泽泻醇A、泽泻醇B和23-乙酰泽泻醇B 6个共有峰，其含量波动范围分别为0.028 7~0.033 1，0.029 5~0.036 6，0.012 0~0.019 4，0.102 2~0.143 9，0.469 3~0.701 2，0.425 5~0.730 8 mg·mL^-1，15批样品指纹图谱相似度为0.979~0.996。主成分分析和PLS-DA将15批样品按照泽泻的产地不同分为3类。结论 该方法快速简单、精密度高、稳定性强、重复性好，基本体现了泽泻汤的整体化学成分特征，可为泽泻汤开发和应用的质量控制提供参考。     

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.

     

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.     

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.     

Glycofection: The Ubiquitous Roles of Sugar Bound on Glycoplexes

Glycofection (transfection by using sugar-substituted polylysine) was assessed in order to provide an alternative to viral vectors for the transfer of genes into vascular smooth muscle cells. A rabbit vascular smooth muscle cell line (Rb-1 cells) was selectively transfected by using glycoplexes (glycosylated polylysine/pSV2LUC complexes) in the presence of 10 mu M of the fusogenic peptide GALA. A sugar-specific transfection was obtained when the glycofection was conducted for 1 h with glycoplexes containing either alpha Gal, alpha -Glc, alpha -GalNAc, beta -GlcNAc, or beta -GalNAc residues. The gene expression was high after transfection, with glycoplexes bearing alpha Gal, alpha -GalNAc, or beta -GalNAc residues that were weakly internalized, and low with glycoplexes carrying Lact or Rha residues that were well taken up by cells. These results suggest that 1) glycofection can be a good approach for a selective transfer of genes intovascular smooth muscle cells, 2) an efficient uptake of the glycoplexes is not the unique limiting step for an efficient transfection, and 3) the sugar-dependent trafficking of the glycoplexes inside the cells may account for the transfection efficiency.     

直肠癌下切缘病理组织学分析

目的探讨直肠癌逆向浸润与下切缘的安全距离的关系。方法对36例直肠癌Miles手术和Dixon手术后标本的肿瘤下缘1.0cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查,观察直肠癌逆向浸润或转移的距离。结果36例直肠癌标本距癌肿下缘1.0 cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查均为阴性,结论直肠癌远恻逆向浸润或转移未见超过1.0cm,因此认为保肛手术时切除肿瘤远侧肠管(包括系膜)2.0cm是安全的。