西红花苷对大鼠心肌损伤的影响

目的:观察西红花苷(Crocin)经静脉注射(iv)和灌胃(ig)单次给药,对大鼠冠脉结扎所致心肌缺血的影响及多次ig给药对去甲肾上腺素(NE)所致大鼠心肌肥厚模型的影响.方法:采用大鼠冠脉结扎造成心肌缺血模型,分别单次ig或iv给予Crocin,6 h后记录心电图(ECG)测量S点的位移;取出心脏用0.1%氯化硝基四氮唑兰(0.1%NBT)染色,计算心肌梗死面积百分率;测定血清中肌酸激酶(CK)及乳酸脱氢酶(LDH)的含量.同时采用NE 所致大鼠心肌肥厚模型,以Crocin多次i.g给药,观察心肌细胞ATPase活性、羟脯氨酸(Hydroxyproline)及MDA的含量.结果:iv Crocin 50和25 mg·-1,ECG的S点位移和心肌梗死面积百分率,血清CK和LDH的含量均比模型组降低.单次ig Crocin 50和100 mg·kg-1组各项指标与模型组相比无显著性差异.Crocin多次ig给药对NE所致大鼠心肌肥厚无改善作用.结论:西红花苷ig给药,对大鼠冠脉结扎所致心肌缺血及NE所致大鼠心肌肥厚均无改善作用,iv给药可有效改善心肌缺血.临床应用应以iv给药为宜.     

西红花酸对大鼠心肌缺血再灌注损伤能量代谢的影响

目的:研究西红花酸对大鼠心肌缺血再灌注损伤能量代谢的影响.方法:建立大鼠在体心肌缺血再灌注模型,采用高效液相色谱(HPLC)法测定心肌组织中高能磷酸化合物ATP,ADP和AMP的含量,以试剂盒测定心肌组织Na /K -ATPage,Ca2 /Mg2 -ATPase活性和血清乳酸脱氢酶(LDH)及肌酸激酶(CK)活性,考察西红花酸(50,25 mg·kg-1)的保护作用.结果:西红花酸能显著降低血清中LDH和CK水平,提高缺血组织ATP含量和能量物质的储备,保护心肌组织ATPase活性.结论:西红花酸对大鼠心肌缺血再灌注损伤有一定的保护作用.其作用机制可能与增加缺血区心肌能量物质含量,保护ATPase活性,改善能量代谢障碍有关.     

西红花酸对去甲肾上腺素所致原代培养心肌细胞能量代谢和凋亡的影响

目的研究西红花酸对去甲肾上腺素(NE)诱导原代培养心肌细胞能量代谢障碍和细胞凋亡的保护作用。方法1 μmol·L^-1 NE损伤原代培养的心肌细胞,检测细胞培养上清液的LDH、心肌细胞ATPase、线粒体琥珀酸脱氢酶(MSDH)的活力,线粒体膜电位的变化,流式细胞仪检测细胞凋亡,观察西红花酸保护作用。结果模型组细胞培养上清液LDH增加,心肌细胞MSDH和ATPase的活力降低,线粒体膜电位降低,心肌细胞凋亡率增加。西红花酸明显降低培养上清液LDH增加,提高MSDH和ATPase的活力、线粒体膜电位的水平,对心肌细胞的凋亡具有明显的保护作用。结论西红花酸对NE所致的心肌细胞能量代谢障碍和凋亡具有明显的保护作用。     

京尼平苷和西红花酸保肝利胆作用的比较

目的 :比较栀子果实中的 2个主要有效成分京尼平苷和西红花酸的保肝利胆作用。方法 :采用十二指肠给药 ,观察京尼平苷和西红花酸对大鼠胆汁流量的影响。采用小鼠CCl4,对乙酰氨基酚急性肝损伤模型 ,比较 2种药物对血清丙氨酸转氨酶 (ALT) ,天冬氨酸转氨酶 (AST)及肝组织中丙二酰二醛 (MDA) ,还原型谷胱甘肽(GSH) ,谷胱甘肽过氧化物酶 (GSH Px)的影响。结果 :京尼平苷 5 0和 10 0mg·kg-1剂量于给药后 0 .5h均显著增加大鼠胆汁分泌 ,而西红花酸同样 2个剂量于给药后 1h对大鼠胆汁分泌却有抑制作用。京尼平苷和西红花酸均可对抗CCl4和对乙酰氨基酚肝损伤引起的MDA升高 ,GSH含量下降和GSH Px活力降低。肝组织的病理变化也有明显减轻 ,但京尼平苷的作用明显强于西红花酸。结论 :栀子利胆保肝的有效成分主要为京尼平苷。     

西红花酸对多柔比星致大鼠心脏毒性的影响

目的：研究西红花酸减轻多柔比星心脏毒性的作用并探讨其机制。方法：建立多柔比星损伤大鼠心脏模型，灌胃给予西红花酸，观察动物心电图变化，测定血清乳酸脱氢酶（LDH）、肌酸激酶（CK）、超氧化物歧化酶（SOD）、全血谷胱甘肽过氧物酶（GSH—Px）和丙二醛（MDA）的变化，用光镜及透射电镜观察心肌的病理改变。结果：西红花酸可以有效改善多柔比星诱导的大鼠心电图异常，如QRS复合波变宽、Q＆T间期延长、T波高耸以及心率变缓（P〈0．05），阻滞多柔比星引起的总SOD，Cu-Zn-SOD，全血GSH—Px活性降低和LDH，CK活性升高及MDA的升高（P〈0．05）；改善心肌超微结构的病理变化。结论：西红花酸可以减轻多柔比星的心脏毒性。     

西红花苷-1大鼠吸收及排泄的研究

目的:研究经口服给药西红花苷-1的吸收及排泄情况.方法:采用大鼠在体小肠回流实验、西红花苷-1溶液2和4h恒温孵育实验以及灌胃给药吸收及排泄实验.HPLC法测定西红花苷-1的含量.结果:西红花苷-1经大鼠在体小肠回流4h后药量消失率分别为:十二指肠10.1%,空肠9.55%,回肠9.15%,结肠12.24%.在不同肠段的空白回流液中孵育4h,降解率分别为:十二指肠9.85%,空肠10.85%,回肠11.49%,结肠12.64%.大鼠灌胃给药24h后粪及肠内容物药量占给药量的79.9%.在蒸馏水及空白肠回流液中经24h孵育,降解率为15.64%和17.62%.大鼠血和尿中均未检测出西红花苷-1.结论:西红花苷-1口服给药后不能以原形经肠道吸收,有少部分转化为苷元(西红花酸)吸收,但浓度很低.     

西红花苷和西红花酸在小鼠体内抗氧化活性对比研究

目的对比评价西红花苷和西红花酸在小鼠体内抗氧化活性。方法采用硅胶柱层析从栀子中分离西红花酸和西红花苷纯品,普通昆明小鼠灌胃给药西红花酸和西红花苷,剂量分别是西红花酸6.25、12.5和25.0mg·kg-1和西红花苷18.7、37.5和75.0mg·kg-1.d-1,采用测定普通小鼠体内抗氧化指标(SOD、GSH-Px、TAOC和MDA)的方法对比评价西红花酸和西红花苷-1体内抗氧化活性。结果两种化合物都能明显提高小鼠肾脏和肝脏的SOD,肝脏的GSH-Px,心脏和肾脏的TAOC,降低血浆的MDA。结论西红花酸和西红花苷-1具有相似的体内抗氧化活性,其主要活性部位可能是肝脏和肾脏。     

西红花酸体内外抗氧化作用的研究

目的研究西红花酸体内外抗氧化作用,以探讨其抗AS作用机制。方法采用次黄嘌呤/黄嘌呤氧化酶反应体系产生O2-,观察西红花酸对O2-的清除作用;分离LDL,观察西红花酸对铜离子诱导的LDL氧化的影响;大鼠灌胃给予西红花酸,观察其对血清TAC及SOD、GPX等抗氧化酶活性、血清氧化易感性的影响。结果西红花酸能有效清除次黄嘌呤/黄嘌呤氧化酶反应体系产生的O2-,抑制铜离子诱导的LDL氧化修饰。西红花酸能明显提高大鼠血清SOD、GPX等抗氧化酶活性,提高血清抗氧化能力。结论西红花酸具有良好的体内外抗氧化活性,能明显提高血清及LDL抗氧化能力,这可能是其抑制AS主要机制之一。     

西红花酸对三氧化二砷诱导大鼠心肌损伤的保护作用

目的 探讨西红花酸对三氧化二砷(As203)所致大鼠心肌损伤的保护作用.方法 40只SD大鼠随机均分为对照组,模型组和西红花酸25、50 mg ? kg-1组,分别每日上午腹腔注射生理盐水或相应剂量西红花酸,6h后模型组和西红花酸组腹腔注射As203 5 mg·kg-1诱导心肌损伤模型,连续10 d.检测心电图,观察心...     

西红花苷对低密度脂蛋白所致鹌鹑内皮细胞损伤的保护作用

目的探讨西红花苷对低密度脂蛋白(LDL)所致内皮细胞损伤的保护作用。方法在体外培养牛主动脉内皮细胞中,加入不同剂量的西红花苷培养12 h后,再加入50μg.ml-1的LDL继续培养24 h,测定培养液中NO含量,测定细胞中一氧化氮合酶(NOS)的活性。在鹌鹑饮食性动脉粥样硬化模型上,观察西红花苷连续9周预防性给药对血清LDL和血清NO的影响。结果西红花苷可浓度依赖性地提高细胞内NOS的活性(P<0.01),使细胞合成分泌的NO含量升高(P<0.01)。西红花苷能显著降低血清LDL水平,使血清NO含量提高。结论西红花苷对LDL所致内皮细胞损伤有保护作用。     

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.