杨芽黄素生物活性的研究进展

杨芽黄素是植物体内一种重要的活性成分，属于黄酮类化合物，具有广泛的生物活性，例如抗肿瘤、抗氧化、抗炎、止泻、抗菌、抗化感、杀虫等作用。其中，关于其抗肿瘤作用的报道比较详细，杨芽黄素对不同的肿瘤细胞具有不同的作用机制。近年来，杨芽黄素的抗过敏、抗骨质疏松、神经保护等药理活性也逐渐被发现。此外，其在体内代谢过程中可去甲氧基化生成白杨素，但药动学方面研究仍相对较少。本文首次对杨芽黄素的生物活性和药动学的研究进行了系统总结，以期为研究者了解杨芽黄素的研究进展提供参考依据。     

聚乙烯亚胺单独及与三种抗菌药物联用对白念珠菌的体外抗菌活性

目的评估多支链的阳离子高分子聚合物——聚乙烯亚胺(PEI)单独及与三种不同类别的常规抗菌药物(两性霉素B、氟康唑和多黏菌素B)联合使用对白念珠菌(MY7245和MY7238)的两种临床分离物的抗真菌活性。方法通过体外实验测定不同分子质量聚乙烯亚胺单独及与三种不同类别的常规抗菌药物联合使用对两株白念珠菌的最小抑菌浓度和杀灭时间,确定PEI单独及联合使用的体外抗真菌活性。结果分子量在2～745ku范围内的PEI均对这两种白念珠菌产生很好的抗真菌活性,且分子量小的PEI比分子量大的PEI的抗菌作用更显著。与单独作用的PEI相比,分子量较大的PEI与常规药物联合使用时可产生较强的协同作用。在体外致死研究实验中可以看到,PEI-两性霉素B和PEI-氟康唑结合物可以提高抑菌作用,但PEI-多黏菌素B结合物却拮抗抑菌作用。结论PEI单独与联合使用均对白念珠菌产生很好的抗菌效果。     

米诺环素对白念珠菌抗菌活性的实验室研究

目的 探究米诺环素在白念珠菌感染中的体外抗菌活性.方法 用K-B纸片扩散法对临床标本分离出的白念珠菌进行抗菌药物包括米诺环素的药敏试验,观察并记录所有药敏试验中,米诺环素的敏感程度及敏感率.结果 发现32种抗菌药物中只有米诺环素对自念珠菌有抑菌环,有抑菌环并且直径14mm以上的占41%.结论 米诺环素在体外具有抗真菌药的活性.     

查耳酮的合成及体外抗真菌活性

目的合成查耳酮类化合物并测定其抗真菌活性. 方法利用Claisen-Schmidt反应合成查耳酮,并针对四种真菌(白色念珠菌、新生隐球菌、烟曲霉菌、红色毛癣菌)做了体外抗真菌活性筛选. 结果显示所合成化合物大多具有体外抗真菌活性,尤其化合物8, 其针对浅表菌的抗真菌活性与氟康唑相当.本文还对部分查耳酮的合成做了一些探索.结论所合成的查耳酮均有不同程度的抗真菌活性,其化学结构差异与抗菌活性相关.     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。     

吡喃鎓衍生物N2的体外抗真菌活性研究

目的 研究N2系列化合物的抗真菌作用。方法 利用微量液基稀释法考察化合物N2系列化合物的体外抗真菌活性；在菌丝和被膜诱导条件下考察N2化合物对白念珠菌菌丝和被膜形成的抑制效果。结果 N2化合物对临床常见条件致病真菌白念珠菌有明显抗真菌活性；N2化合物可以明显抑制白念珠菌菌丝生长和被膜的形成；N2化合物可以通过损伤白念珠菌细胞膜和细胞壁发挥杀菌作用。结论 N2化合物具有较为广泛的抗真菌谱，能起到明显的体外抗真菌效果，对真菌菌丝和生物被膜的形成均有明显的抑制作用，可以认为N2化合物具有抗真菌潜力，可作为先导化合物，指导进一步改造。筛选获得了具有抗真菌活性的N2化合物，为抗真菌药物研发和解决真菌耐药问题提供新思路。     

益智仁化学成分、药理作用及质量标志物研究进展

益智仁Alpinia oxyphylla具温脾止泻摄涎、暖肾缩尿固精的功效，主要含有倍半萜类、二苯庚烷类、黄酮类等成分，其中益智酮甲、圆柚酮和7-表-香科酮等具有调节排尿功能，原儿茶酸、白杨素、圆柚酮和杨芽黄素可改善认知能力，益智酮甲、杨芽黄素、白杨素具抗菌、抗肿瘤作用，原儿茶酸、白杨素具有抗氧化应激、改善糖尿病症状。目前益智仁质量评价方法过于简单，选择的指标成分单一、专属性差、且与功效相关性弱，急需结合新的思想和技术，构建符合中医辨证论治的质量标准体系。     

新型三唑类衍生物的合成及抗真菌活性研究

目的:研究具有萘苄结构的三唑类化合物的抗真菌活性.方法:设计合成了10个三唑类新化合物,其结构通过1H-NMR、MS确证,选择8种真菌为实验菌株,进行体外抑菌活性测试.结果:所有化合物对所选真菌均表现出了一定的抑菌活性,部分化合物对白念珠菌的MIC80值＜0.125μg/ml,是伏立康唑活性的16倍.结论:引入萘环和烷基侧链的目标化合物都具有抗真菌活性.     

鬼箭锦鸡儿中紫檀烷类化合物抗真菌活性研究

目的 研究鬼箭锦鸡儿中紫檀烷类化合物的抗真菌活性。方法 在生物活性指导下,利用聚酰胺、硅胶常规色谱和制备型高效液相色谱方法进行化合物分离,采用波谱技术和化学方法鉴定化合物的结构。最低抑菌浓度(MIC)测定参照美国国家临床实验室标准化委员会(NCCLS)推荐的M27-A方案中的微量肉汤稀释法。结果 鬼箭锦鸡儿整株植物氯仿部分显示好的抗真菌活性,活性追踪分离得到五个紫檀烷类化合物,分别是3-甲氧基高丽槐素(1)、高丽槐素(2)、3-甲氧基-9羟基紫檀烷(3)、3,9-二甲氧基紫檀烷(4)和3-甲氧基-4,9二羟基紫檀烷(5),其中化合物2面对三种念珠菌菌株,显示出潜在的抗真菌活性,最低抑菌浓度范围为6.25~25 μg·mL^-1。结论 所有化合物均为首次从该植物分离得到,并且生物活性结果确认紫檀素类化合物是有效的抗真菌成分。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Hyperkalaemia in patients in hospital

A survey of all laboratory blood specimens with a plasma potassium concentration greater than or equal to 5.5 mmol/L was conducted over a three month period. Of 331 specimens with hyperkalaemia, 71 were excluded because the specimens was haemolysed, old or contaminated. The laboratory served a population of 348,561 and during this time measured the plasma potassium on 25,016 occasions. Sixty-six outpatients and 20 neonates were not evaluated. The survey was undertaken on 86 of 102 inpatients (46 males), 48 of whom were over 66 years of age. Fifty-seven patients were admitted under a medical service and 29 under a surgical service. Fifty-nine had a single episode of hyperkalaemia. Thirty-two underwent a surgical procedure. The commonest contributing factor was impaired renal function which was present in 71 (83%) patients. Although a definitive causative role for drugs could be identified in only five patients, in 52 (60%) patients drugs were a contributing factor (potassium supplements 24, ACE inhibitors 16, nonsteroidal antiinflammatory drugs 12). Thirty-five of the 86 (41%) patients died during their hospital admission. Nineteen of the 35 deaths occurred within three days of the hyperkalaemia being recorded. A normal plasma potassium was eventually documented in 50 of the 86 patients. Of the remaining 36 patients, 25 (69%) subsequently died. In general the treatment of patients with hyperkalaemia focused on identifying and treating the underlying cause. Hyperkalaemia must always be considered seriously and regard given to the overall clinical status of the patient, with particular attention to drug therapy, renal and cardiac function, acid base status and the possibility of sepsis.