玉郎伞提取物对大鼠心肌缺血再灌注损伤的保护作用

目的:研究玉郎伞(YLS)对心肌缺血再灌注损伤(MIRI)的影响.方法:以Wistar大鼠制备MIRI模型(结扎冠状动脉5 min后再灌注30 min),观察YLS对心肌梗死面积及心肌组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力及血清中乳酸脱氢酶(LDH)、肌酸磷酸激酶(CK)活性生化指标的影响.结果:YLS明显降低心肌梗死范围、提高心肌组织中SOD活力、降低其MDA含量,同时降低血清中CK和LDH活力(P<0.01或P<0.05).结论:YLS对大鼠心肌缺血再灌注损伤具有显著的保护作用.     

甘草酸二铵对大鼠心肌缺血再灌注损伤脂质过氧化及心肌酶活性的影响

目的:观察甘草酸二铵(DG)对大鼠心肌缺血再灌注损伤脂质过氧化及心肌酶活性的影响。方法:雄性wistar大鼠30只,随机分为假手术组、缺血再灌注组和DG20mg·kg-1组。每组10只。采用在体大鼠心肌缺血30min再灌注60min损伤模型,再灌注60min后分别用比色法测定心肌丙二醛(MDA)含量、超氧化物歧化酶(SOD)、三磷酸腺苷酶(ATP酶)、血清磷酸肌酸激酶(CPK)和乳酸脱氢酶(LDH)水平,并用酶组织化学方法检测心肌组织琥珀酸脱氢酶(SDH)的活性。结果:DG能显著降低心肌组织中MDA含量和SDH的活性(P<0.05,P<0.01),提高SOD和ATP酶活性(P<0.05,P<0.01),并减少心肌CPK和LDH的释放(P<0.05,P<0.01)。结论:DG具有保护大鼠心肌缺血再灌注损伤的作用,其作用机理可能与其降低心肌脂质过氧化,增强心肌细胞SOD、SDH和ATP酶活性有关。     

氟哌啶醇季铵盐衍生物对大鼠心肌缺血再灌注损伤保护作用的研究

目的　研究氟哌啶醇季铵盐衍生物 (F2 )对大鼠心肌缺血再灌注损伤的影响。方法　大鼠冠状动脉左前降支结扎 30min ,再灌注 30min ,于缺血前舌下静脉注射不同剂量F2 (1,2 ,4mg·kg-1)。测定血清肌酸激酶 (CK)、肌酸激酶同工酶MB (CK MB)、乳酸脱氢酶 (LDH)、α 羟丁酸脱氢酶(HBDH)、谷草转氨酶 (GOT)、丙二醛 (MDA)的含量 ,超氧化物歧化酶 (SOD)活性 ;透视电子显微镜下观察心肌形态学改变。结果　F2 能呈量效关系降低由于缺血再灌注引起的心肌损害心肌酶CK、CK MB、LDH、HBDH、GOT的释放 ,保护SOD的活性 ,降低MDA的产生 ;透视电子显微镜下可观察到F2 能减轻缺血再灌注心肌的形态学改变。结论　F2 对大鼠心肌缺血再灌注损伤具有保护作用     

丹参粉针剂对大鼠心肌缺血/再灌注损伤的保护作用

目的:探讨丹参粉针剂(Danshenfenzhenji,DSFZJ)对大鼠心肌缺血/再灌注损伤的保护作用。方法:通过冠脉结扎、再通手术建立大鼠心肌缺血/再灌注损伤模型,测定各组动物心电图ST段变化、血清肌酸激酶(CK)、乳酸脱氢酶(LDH)活性及观察心肌组织病理学改变,观察药物的心肌保护作用。结果:与模型组比,DSFZJ低、高剂量组(iv,40,250 mg·kg~(-1))心电图ST段抬高值明显下降(P＜0．01),大鼠血清CK和LDH活性显著降低(P＜0．01),心肌组织病理损伤得到明显改善。结论:DSFZJ对大鼠心肌缺血/再灌注损伤具有良好的保护作用。     

异甜菊醇对大鼠在体心肌缺血再灌注损伤的保护作用

目的在大鼠在体心肌缺血再灌注模型上进一步证实异甜菊醇对缺血再灌损伤心肌的保护作用。方法麻醉大鼠结扎左冠状动脉30min后再灌注90min。结扎前10min静脉注射异甜菊醇。心电图连续观察大鼠心室纤颤(VF)和室性心动过速(VT)的发生率;全自动生化分析仪测定血清乳酸脱氢酶(LDH)和肌酸激酶(CK)活性;测定心肌梗死范围;光学显微镜和电镜观察心肌组织学和超微结构改变。结果异甜菊醇0.5～2.0mg·kg-1有效减少大鼠心肌缺血再灌期VF和VT发生率,减少心肌梗死范围,降低血清LDH和CK活性。光镜及电镜观察可见异甜菊醇处理组心肌组织形态学及超微结构损伤明显轻于缺血再灌对照组。结论异甜菊醇对大鼠缺血再灌注损伤心肌有保护作用。     

参麦注射液对再灌注性大鼠心肌细胞保护的研究

目的:探讨参麦注射液对再灌注性大鼠心肌细胞保护的作用机制.方法:结扎冠状动脉前降支复制大鼠心肌缺血再灌注损伤模型,测定心肌组织丙二醛(MDA)含量及结构型、诱导型一氧化氮合酶(cNOS,iNOS)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、血清肌酸激酶(CK)的活性.结果:参麦注射液组心肌组织cNOS、SOD、GSH-Px活性高于缺血再灌注组(P＜0.01),MDA含量、iNOS及血清CK活性低于MI/R组(P＜0.01).结论:参麦注射液保护心肌再灌注性损伤的作用与其抑制iNOS活性、激活cNOS、提高心肌抗氧化能力、清除氧自由基、减轻细胞膜脂质过氧化状态相关.     

碘化正丁基氟哌啶醇对兔心肌缺血再灌注损伤血流动力学和心肌组织中酶的影响

目的　评价碘化正丁基氟哌啶醇 (N n butylhaloperi doliodide ,F2 )对心肌缺血再灌注损伤的保护作用 ,并探讨其作用机制。方法　结扎兔冠状动脉左室支 ,制成急性心肌缺血再灌注损伤模型 ,缺血前 5min ,静脉推注F2 ,观察在急性缺血和再灌注状态下血流动力学的变化及再灌注后心肌组织中超氧化物歧化酶 (SOD)、丙二醛 (MDA)、肌酸激酶(CK)、ATP酶的变化。结果　F2能剂量依赖地改善兔心肌缺血再灌注后的血流动力学变化 ,MAP、LVSP、±dp/dtmax均较缺血再灌注对照组升高 ,LVEDP有所降低 ;还能剂量依赖性地降低MDA的产生 ,保护心肌组织SOD的活性和Ca2 + ATPase、Na+ ,K+ ATPase的活性 ,保护心肌酶CK的释放。结论　F2对心肌缺血再灌注损伤有保护作用。     

葡萄糖酸锌对大鼠缺血再灌注损伤心肌细胞凋亡和细胞超微结构的影响

目的观察心肌缺血再灌注损伤过程中心电图变化,肌酸激酶（CK）和乳酸脱氢酶（LDH）活性,细胞凋亡和心肌细胞超微结构的变化,分析葡萄糖酸锌对心肌的保护作用及其可能机制。方法建立大鼠在体心肌缺血再灌注损伤模型。用心电监测心律失常发生率、比色法测定血清中CK,LDH、流式细胞仪检测细胞凋亡和电镜观察心肌细胞超微结构。结果与模型组相比,葡萄糖酸锌三个不同剂量组大鼠心律失常发生率、血清中CK和LDH活性、细胞凋亡指数降低（P〈0.01）,心肌细胞超微结构损伤明显减轻。结论葡萄糖酸锌对缺血再灌注损伤心肌具有保护作用,可能与其抑制细胞凋亡和减轻心肌细胞超微结构病理改变有关。     

依布硒林对大鼠心肌缺血再灌注损伤的保护作用

目的：探讨依布硒林（Ebs）对大鼠心肌缺血再灌注损伤的保护作用。方法：结扎大鼠冠状动脉左前降支，使心肌缺血30min，再灌注60min，制成急性心肌缺血再灌注损伤模型，缺血前10min，腹腔注射Ebs。动态观察心电图（ECG）变化，同时监测心电图ST段的变化。再灌注结束时，测定血清肌酸磷酸激酶（CK），乳酸脱氢酶（LDH），心肌超氧化物歧化酶（S（）D）活性和谷胱甘肽过氧化物酶（GSH-Px）活性，及心肌丙二醛（MDA）含量。结果：Ebs（1，2，4mg·kg^-1）能减轻心肌心电图ST段变化，降低血清CK、LDH活性，提高心肌SOD和GSH-Px活性，减少心肌MDA含量。结论：Ebs对心肌缺血再灌注损伤有保护作用，其作用与减少脂质过氧化物和增加内源性抗自由基物质的产生有关。     

心达康片对心肌缺血再灌注损伤模型大鼠的保护作用研究

目的:研究心达康片对心肌缺血再灌注损伤模型大鼠的保护作用。方法:采用结扎冠状动脉左前降支30min后再灌注120min的方法复制大鼠心肌缺血再灌注损伤模型。实验分为假手术(等容生理盐水)组、模型(等容生理盐水)组、盐酸地尔硫(14mg/kg)组与心达康高、中、低剂量(6、4、2mg/kg)组,灌胃给药,给药7d后复制模型。检测大鼠血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性与心肌细胞中三磷酸腺苷(ATP)酶活性;免疫组化法测定B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的表达。结果:与假手术组比较,模型组大鼠血清中CK、LDH活性显著增强,SOD和GSH-Px活性显著减弱,心肌细胞ATP酶活性显著减弱,Bax表达显著增强,Bcl-2表达显著减弱(P<0.01);与模型组比较,心达康高、中、低剂量组大鼠血清中CK、LDH活性显著减弱,SOD和GSH-Px活性显著增强,心肌细胞ATP酶活性显著增强,Bax表达显著减弱,Bcl-2表达显著增强(P<0.01或P<0.05)。结论:心达康片对心肌缺血再灌注损伤模型大鼠具有明显的保护作用,其机制可能与其增强机体清除自由基能力,改善心肌细胞ATP酶的能量代谢,以及抑制心肌缺血后心肌细胞凋亡有关。     

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.