槲皮素对鼻咽癌CNE-2Z细胞增殖的影响及机制研究

目的探讨槲皮素对鼻咽癌CNE-2Z细胞增殖的影响及机制,为槲皮素在抗肿瘤临床应用提供理论基础。方法应用MTT法检测槲皮素对人鼻咽癌CNE-2Z细胞增殖的影响,RT-PCR检测槲皮素对CNE-2Z细胞,COX-2、p65和Survivin mRNA表达的影响。结果 MTT结果显示槲皮素对CNE-2Z细胞的生长抑制作用呈现明显的浓度依赖性和时间依赖性（P〈0.01）。槲皮素能呈时间依赖性的抑制CNE-2Z细胞COX-2、p65和Survivin mRNA的表达（P〈0.01）。结论槲皮素呈现明显的浓度依赖性和时间依赖性抑制CNE-2Z细胞的增殖,其作用机制与下调COX-2、p65和Survivin mRNA的表达密切相关。     

槲皮素对高同型半胱氨酸血症家兔血管内皮细胞的保护作用

目的　评估槲皮素对高同型半胱氨酸血症家兔血管内皮细胞的影响。方法　制造家兔高同型半胱氨酸损伤血管内皮细胞模型 ,同时灌胃给予槲皮素 5 0、10 0和 2 0 0mg·kg-1,30d后采血进行循环内皮细胞计数 ,测定血清MDA、SOD、NO和血浆ET ,取胸主动脉作血管反应性测定 ,并进行组织学检查。结果　与损伤模型组相比 ,槲皮素给药组循环内皮细胞降低 ,MDA、ET水平降低 ,而NO和SOD水平升高 ,对ACh的内皮依赖性舒张反应趋近正常 ,对NTG的内皮非依赖性舒张反应无影响 ,组织学检查也证实槲皮素有效地对抗高同型半胱氨酸造成的血管内皮细胞损伤。结论　槲皮素对高同型半胱氨酸损伤家兔血管内皮细胞有保护作用。     

槲皮素对过氧化氢诱导的血管内皮细胞周期及NO水平的影响

目的研究槲皮素对人脐静脉血管内皮细胞增殖周期及细胞内一氧化氮产生的影响。方法用过氧化氢诱导血管内皮细胞损伤,采用ＭＴＴ比色法、流式细胞仪观察槲皮素对血管内皮细胞作用及周期的影响;用硝酸还原酶法测定细胞培养液中ＮＯ水平。结果过氧化氢对血管内皮细胞具有损伤作用,槲皮素剂量依赖性促进过氧化氢诱导血管内皮细胞的增殖,而且主要是Ｓ期和Ｇ２Ｍ期细胞比率增加;槲皮素可减少过氧化氢诱导的血管内皮细胞释放乳酸脱氢酶及促进过氧化氢诱导血管内皮细胞内ＮＯ水平的增加。结论槲皮素可保护过氧化氢诱导血管内皮细胞的损伤及修复,其作用可能与ＮＯ的水平有关。     

槲皮素抑制血管生成作用的实验研究

目的　研究槲皮素 (Quercetin)对血管生成和培养的人脐静脉内皮细胞 (HUVEC)的影响。方法　采用生长因子 (血管内皮细胞生长因子VEGF、碱性成纤维细胞生长因子bFGF)诱导的鸡胚绒毛尿囊膜 (CAM)血管增生模型观察槲皮素对血管生成的影响 ;利用培养的HUVEC ,用MTT法观察槲皮素抑制内皮细胞增殖的作用 ;流式细胞仪观察槲皮素对HUVEC细胞周期的影响。结果　槲皮素 (0 1、0 0 5和 0 0 2 5mmol·L-1)能明显抑制VEGF诱导的CAM小血管生成 ;槲皮素 (0 1和 0 0 5mmol·L-1)能明显抑制bFGF诱导的CAM小血管生成 ;槲皮素 (2 4 0、12 0 μmol·L-1和 6 0 μmol·L-1)对内皮细胞增殖有抑制作用 ,抑制率分别为 6 7 0 %、5 8 1%和39 7% ;槲皮素 (2 4 0、12 0 μmol·L-1)能显著导致HUVEC的S、G2 期阻滞。结论　槲皮素能抑制VEGF和bFGF诱导的血管生成 ,且对内皮细胞增殖具有抑制作用。     

内皮依赖性超极化作用

通过对内皮依赖性松弛作用机制的探讨，作者指出，除一氧化氮外，另外一种不依赖于ｃＧＭＰ的内皮衍生的超极化因子参与内皮依赖性扩血管作用，其超极化及松弛作用的可能与钙依赖性钾通道的开放有关。除ＮＯ和前列环素外，Ｈ２Ｏ２，花生四烯酸的非ＰＧ类代谢物及细胞     

槲皮素对兔离体肠平滑肌张力的影响及其机制

目的:观察槲皮素对兔离体回肠平滑肌肌张力的影响,并探讨其作用机制。方法:试验采用经典的离体小肠灌流技术,观察槲皮素(quercetin,Que)对回肠平滑肌自主收缩活动以及乙酰胆碱(acetylcholine,Ach)、氯化钡及组胺(histamine)所致痉挛性收缩肠平滑肌张力的影响。结果:槲皮素(20,60,100mol.L-1)能剂量依赖性的抑制家兔离体小肠平滑肌自发性收缩,对乙酰胆碱,组胺和氯化钡所致的兔离体肠痉挛性收缩也具有剂量依赖性抑制作用。在无钙台式液中,槲皮素可明显抑制Ach引起的回肠平滑肌收缩(P<0.01),亦能使氯化钙量效曲线下移。槲皮素对Bay K8644(0.5mol.L-1)引起的回肠平滑肌收缩亦有明显抑制作用(P<0.01)。结论:槲皮素明显抑制了家兔离体小肠平滑肌的收缩活动,其机制与抑制外钙内流及内钙释放有关。     

槲皮素对TNFα诱导的内皮细胞与中性粒细胞粘附的抑制作用

目的:研究槲皮素对TNFα诱导的内皮细胞与中性粒细胞粘附的抑制作用及作用机制.方法:用髓过氧化酶法测定中性粒细胞与内皮细胞的粘附,ELISA法测定内皮细胞粘附分子的表达. 结果:TNFα通过增加/诱导内皮细胞ICAM-1, VCAM-1及E-selectin的表达而剂量、时间依赖性地增加内皮细胞与中性粒细胞的粘附.槲皮素可剂量依赖性地抑制上述粘附,其作用机制为抑制TNFα诱导内皮细胞上述3种粘附分子的表达.结论:槲皮素通过抑制ICAM-1, VCAM-1及E-selectin的表达而降低TNFα诱导的内皮细胞与中性粒细胞的粘附.     

槲皮素微乳凝胶制备及体外透皮研究

目的制备槲皮素微乳凝胶,并对其性能及透皮效果进行研究。方法根据已优化的槲皮素微乳的处方并将微乳制成凝胶,采用Franz扩散池对槲皮素微乳凝胶的体外透皮情况进行考察。结果从体外透皮实验可见,与槲皮素混悬液凝胶比较,槲皮素微乳凝胶的体外透过量明显增加(P0.05)。结论槲皮素微乳凝胶的制备工艺可行,且能促进槲皮素的透皮转运量。     

一个槲皮素衍生物对大鼠主动脉内皮细胞氧化与凋亡的保护作用(英文)

甲氧基甲醚异戊烯基槲皮素是一个新合成的槲皮素衍生物, 它比槲皮素有更强的细胞保护作用。本文进一步研究了它对大鼠血管内皮细胞的保护作用和可能的机制。甲氧基甲醚异戊烯基槲皮素(2.5-10 μmol/L)可显著提高H2O2损伤的大鼠血管内皮细胞存活率, 其作用强于槲皮素和维生素E。但在无细胞反应体系甲氧基甲醚异戊烯基槲皮素不显示抗氧化作用。甲氧基甲醚异戊烯基槲皮素(5-10 μmol/L)显著提高H2O2损伤大鼠血管内皮细胞的培养液NO水平和SOD活性, 2.5-10 μmol/L可显著增加培养液中GSH-Px活性, 10μmol/L甲氧基甲醚异戊烯基槲皮素显著降低MDA水平。甲氧基甲醚异戊烯基槲皮素(2.5-10 μmol/L)可以非常明显地减少H2O2诱导的RAECs凋亡率。可见甲氧基甲醚异戊烯基槲皮素的细胞保护作用可能归因于它促进内皮细胞NO释放, 增加细胞内SOD和GSH-Px酶生成, 从而减少脂质过氧化; 抑制细胞凋亡也是它的重要机制之一。该发现提示: 甲氧基甲醚异戊烯基槲皮素有可能成为一个对动脉粥样硬化或其它血管损伤相关疾病有益的抗氧化剂。     

俄色叶和俄色果不同提取部位对大鼠胸主动脉的舒张作用

目的:研究俄色叶、俄色果不同提取部位及俄色叶主要成分根皮苷、根皮素对SD大鼠离体胸主动脉环的舒张作用。方法:采用离体血管灌流实验,通过累计给药法,观察俄色叶、俄色果不同提取部位及根皮苷、根皮素对基础状态、氯化钾(KCl,60 mmol·L~(-1))预收缩的SD大鼠离体胸主动脉环张力的影响。结果:俄色叶及俄色果不同提取部位和根皮苷对基础状态的胸主动脉血管环均无显著影响,对氯化钾预收缩的胸主动脉血管环具有浓度依赖性的舒张作用。根皮素对静息状态的血管有收缩作用,而对氯化钾预收缩的胸主动脉有舒张作用,表现为双向调节作用。结论:俄色叶降压效果强于俄色果,其中有效成分根皮素作用强于根皮苷。其降压机制之一可能为抑制血压依赖性钙通道的开放,减少细胞外钙内流,使细胞内Ca~(2+)浓度下降而舒张血管。     

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.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

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.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

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.