高效液相色谱法测定连翘中连翘酯苷的含量

目的　建立连翘中连翘酯苷的含量测定方法。方法　 HPL C法 ,采用 C1 8柱 ,乙腈 -水 -醋酸 (1 5∶ 85∶ 0 .2 )为流动相 ,检测波长为 332 nm,柱温室温 ,流速为 1 .0 m L· min-1 。结果　连翘酯苷在 0 .0 1 0～ 0 .81 0 g· L-1 范围内线性关系良好 (r =0 .9999) ,平均回收率为 1 0 0 .5 % ,RSD 1 .6 1 %。结论　该法简便快速 ,重现性好 ,适于连翘中连翘酯苷的定量分析     

太行山区不同产地连翘中连翘苷、连翘酯苷A的含量测定

目的：采用HPLC法测定太行山区不同产地、不同采集时间连翘中连翘苷及连翘酯苷A的含量。方法：采用Agilent ZORBAX Eclipse XDB-C18（250mm×4.6mm,5μm）色谱柱,测定连翘苷以乙腈-水（25∶75）为流动相,等度洗脱;流速为1.0ml·min-1;检测波长为277nm。测定连翘酯苷A以乙腈-0.4％冰醋酸溶液（15∶85）为流动相,等度洗脱,流速为1.0ml·min-1;检测波长为330nm。结果：连翘苷和连翘酯苷A线性范围分别为0.206～2.060μg和0.120～1.200μg,平均回收率分别为99.52%（RSD=1.74%）和99.63%（RSD=1.21%）。结论：太行山区不同产地连翘中连翘苷和连翘酯苷A含量差异较大,7月份采集连翘中连翘苷、连翘酯苷A含量最高。含量测定方法准确、快速,适用于连翘的质量控制。     

连翘不同部位中连翘酯苷和连翘苷的含量分析

目的:考察连翘不同部位中连翘酯苷和连翘苷的含量。方法:采用 HPLC 法测定连翘根、树皮、枝、叶、花、果实、种子、果壳中连翘酯苷和连翘苷的含量,以 Diamonsil—C_(18)(4.6 mm×250 mm,5μm)为色谱柱,流动相为水(A)-甲醇(B),梯度洗脱(0～14 min,34%B;14～15 min,34%B～43%B;15～23 min,43%B;23～24 min,43%B～45%B;24～34 min,45%B;34～36 min,45%B～80%B;36～40 min,80%B),流速为1 mL·min~(-1),检测波长270 nm。结果:连翘酯苷在连翘的树皮、叶、花、果实和种子中含量较高,在根、枝、果壳含量很低,连翘苷在连翘叶中的含量远高于其他部位。结论:连翘不同部位连翘甘和连翘酯苷的含量有较大差别,中药连翘应增加连翘酯苷作为标识性成分。     

高效液相色谱法同时测定连翘叶中连翘酯苷A和连翘苷含量

目的建立同时测定连翘叶中连翘酯苷A和连翘苷含量的高效液相色谱法。方法采用AgilentZorbaxSB—C18柱（150mm×4．6mm,5μm）,以甲醇-0．1％磷酸溶液（32：68）为流动相,检测波长为227nm,流速为1．0mL／min,进样量为10txL,柱温为30℃。结果连翘酯苷A、连翘苷进样量分别在293．170～3664．624ng（r=0．999980）和333．760—4172．000ng（r=0．999991）范围内与相应峰面积皇良好线性关系,平均回收率分别为97．00％（RSD：1．88％）和99．97％（RSD=2．11％）。结论该法操作简便、结果准确、专属性强,可用于同时测定连翘叶中连翘酯苷A和连翘苷的含量。     

HPLC法测定小儿肺热咳喘口服液中连翘苷和连翘酯苷A的含量

目的建立高效液相色谱法同时测定小儿肺热咳喘口服液中连翘苷和连翘酯苷A的含量。方法采用Phe-nomen Luna C18(4.6 mm×250 mm5,μm)色谱柱,流动相为甲醇-0.2%磷酸溶液梯度洗脱,检测波长为280 nm,流速为1.0 mL·min-1,柱温为30℃。结果连翘苷和连翘酯苷A与其相邻杂质峰能完全分离,连翘苷和连翘酯苷A进样量分别在0.030 3～0.545 4μgr,=0.999 5,0.019 8～0.356 4μgr,=0.999 6浓度范围内线性关系良好,平均回收率分别为99.35%,RSD=0.097%(n=6),99.48%,RSD=0.15%(n=6)。结论本法简便、可靠、准确,可用于该制剂的质量控制。     

门氏护胃方中连翘与其他药材配伍煎煮前后连翘酯苷A和连翘苷提取率变化的研究

目的:考察门氏护胃方中连翘单药及与其他药材配伍煎煮前后连翘酯苷A和连翘苷提取率的变化。方法:采用高效液相色谱法测定连翘单味药材(5 g×7付)、连翘(5 g×7付)与姜半夏配伍、门氏护胃方[包括连翘(5 g×7付)、姜半夏等6味药材]经水煎煮后药液中连翘酯苷A和连翘苷的提取量并计算提取率。色谱柱为Diamonsil C18,流动相为乙腈-0.2%甲酸溶液,梯度洗脱,检测波长为278 nm,柱温为30℃,流速为1.0 m L/min。结果:连翘酯苷A与连翘苷进样量线性范围分别为0.61～6.1、0.246～2.46μg(r=0.999 7、0.999 9),在精密度、稳定性(20 h内)和重复性试验中RSD均<2%(n=6),平均回收率为96.10%～99.37%(RSD≤2.36%,n=6);在连翘单味药材中,连翘酯苷A和连翘苷的提取率分别为96.90%、66.67%;在连翘-姜半夏配伍样品水煎液中,二者的提取率分别为101.61%、54.55%;在门氏护胃方样品水煎液中,二者的提取率分别为98.39%、84.85%。结论:连翘与姜半夏配伍后连翘酯苷A的提取率增加、连翘苷的提取率略有减少;连翘与门氏护胃方中其他药材配伍后,二者的提取率均略有增加。     

RP-HPLC测定抗病毒口服液中连翘苷的含量

目的　以反相高效液相色谱法测定抗病毒口服液中连翘苷的含量。方法　色谱条件为 :ODS柱 ( 4 6mm× 2 5cm ,5 μm) ;流动相 :乙腈 水 ( 2 5∶75 ) ;检测波长 2 77nm ;平均回收率为 10 0 2 2 % ,RSD为 3 6 1% (n =5 )。 结果　该方法简便 ,与样品中其它成分容易分开 ,稳定性与精密度良好。结论　本法可作为抗病毒口服液中连翘苷含量测定的一种方法。     

四季抗病毒合剂制备中连翘酯苷A和连翘酯苷B转移率的研究

目的建立连翘与四季抗病毒合剂中连翘酯苷A和连翘酯苷B的含量测定方法,阐明其在连翘药材至四季抗病毒合剂制剂间的转移率。方法采用超快速液相色谱(UFLC)法,选取3批连翘药材,每批对应5批制剂。结果 1 3批连翘药材中连翘酯苷A的含量分别为12.57,20.26和18.64mg·g~(-1),3批连翘药材中连翘酯苷B的含量依次分别为2.22,3.76和3.07mg·g~(-1);2每批连翘药材对应5批制剂中连翘酯苷A的平均含量分别为1 129.40,1 828.30和1 666.30μg·mL~(-1),每批连翘药材对应5批制剂中连翘酯苷B的平均含量依次分别为224.80,382.60和315.70μg·mL~(-1);3 15批制剂中连翘酯苷A和连翘酯苷B的转移率分别为74.86%和84.95%,RSD分别为0.88%和1.43%。结论该含量测定方法具有简便、稳定、可靠、准确等优点,可作为连翘与四季抗病毒合剂中连翘酯苷A和连翘酯苷B的定量方法;连翘酯苷A和连翘酯苷B的转移率高,表明制剂制备工艺有利于2种有效成分的溶出,为保证制剂疗效提供了理论依据。     

RP-HPLC法测定抗病毒口服液中连翘苷含量

采用 RP- HPL C法测定抗病毒口服液中连翘苷含量。固定相为 Nova- Pak C18反相柱 ;流动相为甲醇 -水 -磷酸 (4 3∶ 57∶ 0 .2 ) ;检测波长为 2 77nm。该方法的线性范围为 0 .4 2～ 4 .2 3μg(r =0 .9999) ,平均回收率为95.6 % ,RSD =3.0 1% (n =6 )。     

高效液相色谱法测定胜红抗炎素胶囊中连翘苷的含量

目的 　采用高效液相色谱法测定胜红抗炎素胶囊中连翘苷的含量。 方法 　色谱柱为KromasilC1 8柱 (1 50× 4 .6mm ,5μm) ,流动相为乙腈∶水 (2 5∶75) ;流速 :1 .0ml·min- 1 ,检测波长为 2 77nm。 结果 　连翘苷的进样量在 0 2～ 2 .0 μg范围内与峰面积呈良好线形 (r =0 .9995) ;平均回收率为 99 82 % ,RSD为 1 0 9% (n =9)。 结论 　该法简便 ,结果可靠 ,可有效地用于胜红抗炎素胶囊的质量控制。     

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.     

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.

     

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.     

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.     

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.     

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.