毛细管电泳法测定娑罗子药材中的黄酮苷类成分

目的:建立高效胶束毛细管电泳法分离测定娑罗子药材中的黄酮苷类成分的分析方法。方法:应用 HPCE 对娑罗子中分离得到的3种黄酮苷进行分析测定,以0.2mol·L~(-1)硼砂-0.06mol·L~(-1)SDS(含15%乙腈,pH 为9.0)的缓冲液为电泳介质,压力进样,在25℃,20kV 恒压下电泳分离,并在270nm 波长处检测。结果:娑罗子中的3种黄酮苷在30min 内可达到分离。结论:该方法可用于娑罗子药材及其制剂中黄酮苷类成分的分析。     

以盐酸去甲万古霉素为手性选择剂毛细管电泳法分离西替利嗪对映体

目的:建立以阳离子表面活性剂碘化四丁基铵为电渗流改性剂,以盐酸去甲万古霉素为手性选择剂的毛细管电泳法分离西替利嗪对映体。方法:考察了盐酸去甲万古霉素浓度、Tris 浓度和缓冲液 pH 对分离的影响,对分离条件进行了优化。结果:在含0.04 g·L~(-1)碘化四丁基铵和1.0 mmol·L~(-1)盐酸去甲万古霉素的25 mmol·L~(-1)Tris 磷酸缓冲液(pH 4.5)的运行电解质体系中,西替利嗪对映体在分离电压为20 kV 的条件下得到良好分离,西替利嗪对映体分离度达1.8。结论:本法可用于西替利嗪对映体的分离。     

毛细管区带电泳分离／安培检测儿茶酚胺药物

目的:建立毛细管区带电泳(CZE)分离/安培检测左旋多巴(DP)、多巴胺(DA)、肾上腺素(EP)、去甲肾上腺素(NE)、5-羟色胺(5-HT)5种儿茶酚胺类神经递质(CAs)药物的方法。方法:采用石英毛细管柱(60 cm×50μm),含8 mmol·L~(-1)对-(季铵盐)杯[4]芳烃(QAC4A)的125 mmol·L~(-1)磷酸氢二钠溶液(Na_2HPO_4,pH 7.0)为缓冲液,分离电压6 kV,分离 CAs 并利用 Cu 微粒修饰碳纤维电极检测。结果:优化条件下5种 CAs 被基线分离,回收率为92%～105%,5种 CAs 在0.2～1000μmol·L~(-1)浓度内呈良好线性关系,最低检测限为0.2 μmol·L~(-1)。应用该方法成功地测定了5种 CAs 注射液、正常人和嗜铬细胞瘤患者尿样。结论:本法用于分离并检测 CAs 药物,具有准确、灵敏、简便的特点,适合该类药品分析。     

胶束毛细管电泳测定枇杷叶中熊果酸和齐墩果酸的含量

目的:建立测定枇杷叶中熊果酸和齐墩果酸含量的毛细管电泳方法。方法:采用胶束毛细管电泳法(MECC),未涂层弹性石英毛细管(75 μm×60 cm,有效长度50 cm);压力进样,压力:3.0×10~3 Pa;进样时间:5 s;分离电压:24 kV;柱温:25℃;检测波长:200 nm;运行缓冲液:30 mmol·L~(-1) SDS,20 mmol·L~(-1)羟丙基-β-环糊精,5%乙腈,40 mmol·L~(-1)硼砂溶液(pH9.4);运行时间:30 min。结果:测得熊果酸和齐墩果酸的线性范围分别为42.5～680 μg·mL~(-1)(r=0.9989)和33.0～660μg·mL~(-1)(r=0.9994),平均回收率(n=5)分别为98.1%(RSD 为3.3%)和97.8%(RSD 为2.9%)。结论:方法准确可靠,适合于枇杷叶中熊果酸和齐墩果酸的含量测定。     

胶束电动毛细管电泳法分离6种生物碱基

目的:采用胶束电动毛细管电泳法(MECC)分离腺嘌呤(A)、鸟嘌呤(G)、胞嘧啶(C)、胸腺嘧啶(T)、茶碱和咖啡因6种生物碱基。方法:20℃、18 kV 应用电压下,检测波长270 nm,在 35 mmol·L~(-1)十二烷基硫酸钠(SDS)-10 mmol·L~(-1)硼砂(pH 9.0)运行缓冲液中电泳分离。结果:6种碱基8 min 内达到基线分离;在10～500 mg·L~(-1)浓度范围内呈良好线性关系;相关系数为0.9995～0.9999;检出限为12.5～100μg·L~(-1),加样回收率在96.1%～105.2%。并用于3种药物和茶叶中生物碱基含量的测定。结论:方法简便、快速,灵敏度高,可用于分析和测定含生物碱基的药物和饮料。     

高效毛细管胶束电泳法测定血清中氟尿嘧啶的含量

建立了血清中5-FU血药浓度的高效毛细管胶束电泳分离测定方法。测定条件为未涂渍石英毛细管(27cm×75μm);电极缓冲液(25mmol·L~(-1)硼酸-硼砂缓冲液pH9.0加50mmol·L~(-1)SDS);操作电压500V/cm;检测波长266um;压力上样10s;5-FUDR为内标。实验结果 血清中5-FU的含量在0.05～50μg·ml~(-1)之间呈良好的线性关系,r=0.999 9,平均回收率 日内回收率为98.3％(RSD=3.8％);日间为102.6％(RSR=5.2％)。     

坦洛新对映体的HS-β-环糊精的HPCE手性拆分研究

目的:建立坦洛新对映体的毛细管电泳手性拆分法。方法:10 mmol·L~(-1)HS-β-环糊精为手性添加剂,以25 mmol·L~(-1)的磷酸缓冲液,用三乙醇胺调节 pH 为3.0为背景电解质溶液,运行电压为-20 kV,毛细管温度为20℃,检测波长200nm,对坦洛新对映体进行手性分离研究,并考察了多种因素对分离的影响。结果:在该毛细管电泳条件下,坦洛新对映体能得到基线分离。结论:本方法简单、快捷、经济,可适用于坦洛新对映体分离和纯度检查。     

胶束毛细管电泳法测定家兔体内的丹参素及药代动力学和组织分布

目的:建立片参中丹参素在家兔血浆中的胶束毛细管电泳(MEKC)分析方法,并研究其药代动力学和组织分布。方法:丹参提取液给家兔灌服,采用液-液萃取技术对家兔血浆中的丹参素进行萃取,用胶束毛细管电泳进行测定。MEKC 条件为:熔融石英毛细管75μm×34.5 cm,有效长度26cm,运行缓冲溶液为30 mmol·L~(-1)硼砂 50 mmol·L~(-1)SDS(pH=9.00),运行电压7 kV,检测波长280 nm。结果:该分析方法的线性范围为0.4～400μg·mL~(-1),LOD 为0.08μg·mL~(-1)(S/N=3),LOQ 为0.4μg·mL~(-1),日内精密度的 RSD 为1.1%～5.8%,日间精密度的 RSD 为2.9%～3.4%,平均回收率为85.0%～104.2%。结论:该分析方法灵敏、准确,适合于丹参素的药代动力学及组织分布研究。     

HPCE法同时测定保健品及中成药中的5种苷类成分

目的 建立同时测定中成药及保健品中人参皂苷Rg1、Re、红景天苷、淫羊藿苷、腺苷5种苷类成分含量的毛细管电泳法.方法 采用高效毛细管电泳紫外检测法,运行缓冲液为50 mmol·L-1硼砂-4 mmol·L-1 NaCh(15%甲醇,pH10),分离电压30 kV,温度20 ℃;检测波长205nm.结果 人参皂苷Rg1、...     

西布曲明对映体的毛细管电泳分离及结合常数的测定

目的 采用毛细管电泳法分离西布曲明对映体并测定其结合常数.方法 考察手性添加剂浓度、缓冲溶液pH及浓度、温度、分离电压等因素对分离度的影响,并采用双倒数法计算西布曲明对映体与2,6-二甲基-β-环糊精(DM-β-CD)的结合常数.结果 在12.5 mmol·L~(-1)DM-β-CD、100 mmol·L~(-1)Tris-H_3PO_4(pH 2.5)缓冲液、16℃柱温,30 kV操作电压的毛细管电泳条件下,西布曲明对映体在9 min内获得了良好分离,分离度达2.0;结合常数分别为154.4、173.3 L·mol~(-1).结论 所用高效毛细管电泳方法快速、准确、可靠,适用于西布曲明对映体的分离;结合常数的计算可为研究西布曲明对映体的拆分机理提供依据.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.