美洛昔康贴片抗炎作用实验研究

目的观察局部用美洛昔康贴剂(Mel T)的抗炎作用及其对胃肠道的刺激性。方法采用二甲苯致腹腔毛细血管通透性增加法和二甲苯致耳肿胀法,角叉菜胶诱发足肿胀法以及完全佐剂诱导佐剂性关节炎等实验方法。结果Mel T局部粘贴小鼠20、105、mg/kg,明显抑制二甲苯所致的小鼠耳肿胀和二甲苯引起的皮肤毛细血管通透性的增加,大鼠足部粘贴14、7、3.5 mg/kg,明显抑制角叉菜胶致大鼠足肿胀;对AA大鼠原发性和继发性炎症均有抑制作用,且大鼠胃肠道粘膜出血和溃疡比Mel灌胃组少。结论Mel T有明显的抗炎作用,不良反应小于口服给药。     

四氢黄连碱体内抗炎作用的研究

目的通过多种炎症模型观察四氢黄连碱的体内抗炎作用。方法采用由多种炎性介质参与的角叉菜胶致大鼠足肿胀模型、二甲苯致小鼠耳肿胀模型以及小鼠内毒素休克模型,从整体上评价四氢黄连碱的体内抗炎作用。角叉菜胶致大鼠足肿胀模型分为:空白对照组、四氢黄连碱高剂量组(21 mg/kg)、低剂量组(7 mg/kg)以及阳性药地塞米松组(5 mg/kg),空白对照组给予生理盐水,其余各组给予相应剂量的药物,30 min后,足跖皮下注射角叉菜胶,并分别在致炎前及致炎后1、2、3、4、5 h测量大鼠足趾厚;二甲苯致小鼠耳肿胀模型分为:空白对照组、四氢黄连碱高剂量组(30 mg/kg)、低剂量组(10 mg/kg)以及阳性药地塞米松组(5 mg/kg),空白对照组给予生理盐水,其余各组给予相应剂量的药物,连续给药7 d,末次给药30 min后于小鼠右耳涂抹二甲苯,左耳为对照,l h后处死,取相同部位的耳片并称重;小鼠内毒素休克模型分为:空白对照组、阴性组、四氢黄连碱高剂量组(30 mg/kg)以及低剂量组(10 mg/kg),阴性组和空白对照组给予生理盐水,其余各组给予相应剂量的药物,给药后30 min,阴性组和四氢黄连碱组腹腔注射LPS(20 mg/kg),空白对照组给予等体积的生理盐水,每隔12 h记录1次小鼠的存亡情况,连续观察72 h。结果角叉菜胶致大鼠足肿胀模型中,四氢黄连碱可显著抑制大鼠足肿胀,高剂量组(21 mg/kg)对足肿胀的最大抑制率达到77.82%,低剂量组(7 mg/kg)对足肿胀的最大抑制率为62.39%,和阳性药地塞米松组(5 mg/kg,最大抑制率80.54%)的作用相当;二甲苯致小鼠耳肿胀模型中,四氢黄连碱可显著抑制小鼠的耳肿胀,其中高剂量组(30 mg/kg)对耳肿胀的抑制率达到74.03%,低剂量组(10 mg/kg)对耳肿胀的抑制率为53.93%,和阳性药地塞米松组(5 mg/kg,抑制率64.71%)的作用相当;四氢黄连碱可显著性提高内毒素休克小鼠的存活率,其中高剂量组(30 mg/kg)内毒素休克小鼠72 h内的存活率为70%,低剂量组(10 mg/kg)为40%,四氢黄连碱组的存活率与阴性组(30%)相比差异有统计学意义。结论四氢黄连碱具有较强的抗炎、抗内毒素休克作用,且抗炎机制可能与抑制炎性物质的渗出和炎症细胞因子的分泌有关。     

701跌打镇痛膏抗炎作用的实验研究

目的考察701跌打镇痛膏的抗炎作用,为其临床应用提供实验依据。方法通过角叉菜胶致大鼠足跖肿胀模型、二甲苯致小鼠耳肿胀模型、完全氟氏佐剂致大鼠关节炎模型,考察701跌打镇痛膏的抗炎作用。结果 701跌打镇痛膏单次腹部敷贴给药后能明显降低角叉菜胶致SD大鼠足肿胀的足容积和足肿胀度,药效达峰时间约为给药后4 h;连续腹部敷贴给药5 d后能明显降低二甲苯引起的小鼠耳廓肿胀度,抗炎作用具有明显的量效关系;对大鼠佐剂性关节炎模型未见明显作用。结论 701跌打镇痛膏对急性渗出性炎症具有明显的改善作用,但对免疫性炎症作用不明显。     

草豆蔻挥发油的抗炎作用研究

目的 研究草豆蔻挥发油的抗炎作用.方法 构建二甲苯致小鼠耳肿胀、醋酸致小鼠腹腔毛细血管通透性增加、棉球诱发大鼠肉芽肿及角叉菜胶致大鼠足跖肿胀炎症模型,将草豆蔻挥发油高、中、低剂量组炎症模型鼠的疗效与空白对照组、阳性对照组(地塞米松)相比较,观察草豆蔻挥发油对不同炎症模型的抗炎作用.结果 与空白对照组及阳性对照组相比,高、中剂量草豆蔻挥发油能够降低小鼠毛细血管通透性,并抑制二甲苯致小鼠耳肿胀,减轻大鼠肉芽肿,其中高剂量草豆蔻挥发油(100mg/kg)的抗炎作用与地塞米松组相当.结论 草豆蔻挥发油具有明显的抗炎作用.     

鬼针草总黄酮对急性炎症的保护作用及可能机制研究

目的:研究鬼针草总黄酮(TFB)对急性炎症的保护作用与可能机制.方法:二甲苯诱导急性小鼠耳肿胀,检测耳肿胀度和血清TNF-α、IL-1、IL-6、IL-8含量;氟氏完全佐剂诱导佐剂性关节炎(AA)大鼠原发性炎症,检测足肿胀度和血清TNF-α、IL-1、IL-2、IL-6、IL-8含量,HE染色观察炎症关节病理学变化,免疫组织化学法检测关节软骨组织ASIC1a蛋白.结果:小鼠急性耳肿胀和AA大鼠原发性炎症中,模型组动物血清TNF-α、IL-1、IL-6和IL-8含量均明显升高,TFB(100、200mg/kg)灌胃给药能降低小鼠耳肿胀度和血清TNF-α、IL-1、IL-6、IL-8含量,TFB(67、133mg/kg)可以升高AA大鼠血清IL-2的含量.TFB灌胃给药可以使AA大鼠关节炎性细胞减少,改善病理变化.在AA大鼠原发性炎症中模型组大鼠关节软骨组织ASIC1a表达明显升高,TFB(67、133 mg/kg)组ASIC1a的表达明显降低.相关性分析结果显示,AA大鼠原发性炎症中ASIC1a与血清TNF-α、IL-1、IL-8含量呈正相关.结论:TFB对急性炎症具有保护作用,其抗炎机制可能与调节炎症介质释放有关.     

炎康颗粒的抗炎作用及机制研究

目的 研究炎康颗粒的抗炎作用,并探讨其作用机制.方法 采用巴豆油致小鼠耳肿胀实验模型、角叉菜胶致雄性大鼠足跖肿胀实验模型,观察炎康颗粒对急性炎症的作用;采用大鼠棉球肉芽肿实验模型,观察炎康颗粒对慢性炎症的作用;采用摘除双侧肾上腺的大鼠进行角叉菜胶致足跖肿胀实验及棉球肉芽肿实验,以观察炎康颗粒抗炎作用与下丘脑-垂体肾上腺轴(HPAA)的关系.结果 炎康颗粒8、16 g(生药)/kg连续给药1周,明显抑制小鼠耳肿胀;4、8g(生药)/kg明显抑制由角叉菜胶诱导的大鼠足趾肿胀;明显抑制大鼠棉球肉芽的增生.摘除肾上腺后,炎康颗粒连续给药1周,无明显抗炎作用.结论 炎康颗粒对急性炎症和慢性炎症均有明显的防治作用,其抗炎作用依赖于HPAA系统,并与减少白细胞介素有关.     

复方风湿宁注射液的抗炎作用研究

目的 研究复方风湿宁注射液的抗炎作用.方法采用大鼠角叉菜胶致关节炎模型、大鼠佐剂性关节炎模型和大鼠棉球肉芽肿模型,观察复方风湿宁注射液的抗炎、消肿作用,并测定角叉菜胶诱发的关节炎模型大鼠致炎足炎症渗出液中前列腺素E2(PGE2)的水平.结果与模型组比较,复方风湿宁注射液显著减轻角叉菜胶所致踝关节炎症大鼠的足肿胀度(P＜...     

枇杷叶三萜酸对慢性支气管炎大鼠气道上皮细胞NF-κB和ICAM-1表达的影响

目的 研究原花青素对大鼠佐剂性关节炎的治疗作用并探讨其作用机理。方法 60只雄性SD大鼠随机分为正常对照组、模型对照组、地塞米松治疗组（2mg／kg）、原花青素小剂量组（1．2mg／kg）、原花青素中剂量组（6mg／kg）、原花青素大剂量组（30mg／kg），每组10只．用完全弗氏佐剂制造大鼠佐剂性关节炎（AA）模型，大鼠于致炎后第8天给药，观察各组对AA大鼠足肿胀及体重的影响。第24天处死大鼠，剪下致炎足的对侧足爪，剪碎后浸泡于生理盐水2小时，EIA法测浸泡液中PGE2的含量。同时分离大鼠腹腔巨噬细胞，     

原花青素对佐剂性关节炎大鼠炎性介质的影响

目的 观察原花青素对佐剂性关节炎大鼠炎症介质PGE2、NO和细胞因子IL—β、TNF—α、IL-4、IL-0的影响。方法60只雄性SD大鼠随机分为正常对照组、模型对照组、地塞米松治疗组（2mg／kg）、原花青素小剂量组（1．2mg／kg）、原花青素中剂量组（6mg／kg）、原花青素大剂量组（30mg／kg），每组10只，以完全弗氏佐剂制造大鼠佐剂性关节炎模型。大鼠于致炎后第8天给药，第24天心脏取血，ELISA测血清中IL—β、TNF—α、IL-4、IL—10的含量；并剪下致炎足的对侧足爪，剪碎后浸泡于生理盐水2小时，     

盆炎洁颗粒抗炎作用的研究

目的观察盆炎洁颗粒的抗炎作用。方法采用小鼠耳肿胀、大鼠角叉菜胶性关节炎及塑料环致大鼠子宫炎症模型。结果连续3d灌胃盆炎洁颗粒7．5g生药/kg、22．5g生药/kg可明显抑制二甲苯性小鼠耳肿胀；灌胃4．5g生药/kg、13．5g生药/kg对大鼠关节炎及子宫炎模型均有明显抑制作用，其抗炎强度与阳性药妇炎康片相似。结论盆炎洁颗粒具有良好的抗炎作用。     

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.     

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.     

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.