不同醋制方法对延胡索中延胡索乙素和原阿片碱含量的影响

目的:探讨延胡索不同醋制方法对其延胡索乙素、原阿片碱含量的影响。方法:HPLC法:大连依利特C_(18)色谱柱(250mm×4.6mm,5μm),流动相为甲醇-0.6%冰醋酸(含0.6%三乙胺)(20:80);检测被长为280nm;流速1.0ml·min~(-1);柱温:室温。结果:延胡索乙素、原阿片碱分别在0.25～1.47μg(r=0.999 9),0.20～1.21μg(r=0.999 9)范围呈良好的线性关系,平均回收率分别为104.0%,101.2%,RSD分别为1.8%,1.5%(n=6)。不同醋制方法对延胡索中延胡索乙素和原阿片碱含量影响不一。结论:方法准确,重复性好,延胡索乙素和原阿片碱含量适用于延胡索炮制品的质量控制。临床应用宜规范采用"醋延胡索"。     

反向高效液相色谱法测定妇乐软胶囊中延胡索乙素的含量

目的建立反相高效液相色谱法测定妇乐软胶囊中延胡索乙素的含量。方法采用Shim-Pak vp-ods C18(250 mm×4.6 mm,5μm)色谱柱,0.1%磷酸(pH 6.0)-甲醇为流动相,梯度洗脱,检测波长230 nm。结果延胡索乙素在0.2024-5.06μg线性关系良好(r=1.000)。平均回收率为101.2%,RSD=2.1%(n=5)。结论本法准确、简便、快速、稳定可靠,能用于测定妇乐软胶囊中延胡索乙素的含量。     

胃安宁片延胡索中延胡索乙素的HPLC含量测定

目的:建立HPLC法测定胃安宁片延胡索中延胡索乙素含量测定的方法.方法:采用RP-HPLC法测定.用Agilent XDB C18色谱柱(250mm×4.6mm,5μm),以甲醇-0.1%磷酸溶液(三乙胺调PH值至6.0)(60:40)为流动相,流速为1ml/min,检测波长280nm,柱温为室温,进样量为10μ1.结果延胡索乙素保留时间约为27分钟左右,与其他峰的分离度大于1.5.延胡索乙素的线性范围为0.024-0.476μg,γ=0.9999,平均加样回收率为98.81%(n=5).结论:该方法简便快速,结果准确可靠,可用于延胡索乙素中延胡索乙素的HPLC含量测定.     

HPLC法测定肾石通颗粒(无糖型)中延胡索乙素的含量

目的建立肾石通颗粒(无糖型)中延胡索乙素的含量测定方法。方法采用高效液相色谱法。色谱条件:色谱柱:Diamonsil(钻石)C18(5μm,250×4.6mm);流动相:甲醇-0.1%磷酸(三乙胺调pH6.0)(55∶45);检测波长:280nm;柱温:40℃;流速:1.0mL/min;理论板数按延胡索乙素峰计算不低于3000。结果延胡索乙素在0.1~0.6μg之间线性关系良好,r=0.9996。延胡索乙素平均回收率为99.3%,RSD=0.83%。结论该方法准确,重复性好,可用于肾石通颗粒(无糖型)的质量控制。     

HPLC测定气滞胃痛颗粒中的延胡索乙素

目的采用HPLC测定气滞胃痛颗粒中的延胡索乙素。方法色谱柱为Kromasil C18,流动相为乙腈-水(40:60,磷酸调pH6.2),检测波长为283 nm,流速为1.0 m.lmin-1,柱温为30℃。结果延胡索乙素2.68~100.50μg.ml-1与峰面积的线性关系良好(r=0.9999),平均加样回收率为98.90%,RSD=2.48%。结论所建方法准确、重复性好,可用于气滞胃痛颗粒中延胡索乙素的测定。     

气滞胃痛颗粒质量标准研究

目的建立气滞胃痛颗粒的质量控制方法。方法采用薄层色谱(TLC)法对气滞胃痛颗粒中的香附、枳壳和甘草进行定性鉴别。采用高效液相色谱(HPLC)法对气滞胃痛颗粒中的延胡索乙素进行含量测定,色谱柱采用Alltima C18柱(250 mm×4.6 mm,5μm),以0.1%磷酸溶液(用三乙胺调pH至6.0)-乙腈(59∶41)为流动相,流速为1.0 mL/min,检测波长为280 nm,柱温为30℃。结果枳壳、香附和甘草薄层色谱法鉴别专属性强,延胡索乙素进样量在0.050 1～1.002μg范围内与峰面积呈良好线性关系(r=0.999 9,n=7),延胡索乙素平均回收率为99.94%,RSD=1.60%(n=6)。结论所用方法可准确地定性、定量,重现性好,可用于控制气滞胃痛颗粒的质量。     

HPLC法测定胃安颗粒中延胡索乙素的含量

目的建立胃安颗粒中延胡索乙素的含量测定方法.方法采用高效液相色谱法测定胃安颗粒中延胡索乙素的含量.色谱柱:Hypersil C18柱(4.6mm×250mm,5μm);流动相:甲醇-0.1%磷酸溶液(55∶45);流速:1mL·min-1;柱温:室温;检测波长:280nm.结果延胡索乙素在0.193～0.965μg范围内,进样量与峰面积呈良好的线性关系(r=0.9992),平均回收率为96.59%,RSD=1.99%.结论本法准确、专属性强、重现性好,可作为胃安颗粒中延胡索乙素的含量测定方法.     

HPLC法测定气滞胃痛胶囊中延胡索乙素的含量

目的建立气滞胃痛胶囊中延胡索乙素的含量测定方法。方法采用HPLC法,色谱柱:迪马C18色谱柱,甲醇-0.17%磷酸溶液(每1000mL 0.17%磷酸溶液加入1.8mL三乙胺)(26∶74)为流动相,检测波长280nm。结果延胡索乙素在0.0506~1.2156μg之间线性关系良好,r=0.9999,回收率为98.55%,RSD为1.09%(n=6)。结论该方法操作简单、分离效果好、灵敏度高,可作为气滞胃痛胶囊的质量控制标准。     

高效液相色谱法测定胃康灵胶囊中延胡索乙素的含量

目的:建立以反相高效液相色谱(RP-HPLC)法测定胃康灵胶囊中延胡索乙素含量的方法。方法:色谱柱为Shim-Pack VP-ODS,流动相为甲醇-水-三乙胺溶液(70∶30∶0.5),检测波长为280nm,柱温为25℃,流速为1ml/min。结果:延胡索乙素进样量在0.08μg~0.80μg范围内呈良好的线性关系(r=0.9 999,n=5),平均加样回收率为100.76%(RSD=2.13%,n=6)。结论:本方法简便、快速、可靠,可用于该制剂的质量控制。     

RP-HPLC法测定创灼膏中延胡索乙素的含量

目的建立以高效液相色谱法测定创灼膏中延胡索乙素含量的方法。方法色谱柱为Khim-pack shimadzu C18柱,流动相为乙腈-0.2%磷酸溶液(20∶80),流速为1 mL/min,检测波长为280 nm。结果延胡索乙素浓度在5⁵0μg/mL范围内的线性关系良好(r=0.9999),平均回收率为98.0%(RSD=1.07%)。结论方法简便易行,准确率高,重现性好,为本品的质量控制提供了可靠的方法。     

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.