黄芩苷对大鼠心肌缺血再灌注损伤的保护作用

目的研究黄芩苷对大鼠缺血再灌注损伤的保护作用. 方法结扎大鼠左冠脉前降支40 min 再灌注120 min ,观察黄芩苷对心肌梗死后大鼠心功能、心肌梗死面积和乳酸脱氢酶(LDH)活性、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性等的影响.结果结扎冠脉前5 min给黄芩苷10～40 mgkg-1能改善心肌梗死后大鼠的心功能、减少心肌梗死面积(9%～30%),并能减少梗死后心肌MDA含量、提高梗死后心肌SOD、 LDH的活性. 结论黄芩苷对大鼠缺血再灌注的心肌损伤有保护作用.     

黄芩苷对大鼠心肌缺血再灌注损伤的保护作用

目的　研究黄芩苷对大鼠缺血再灌注损伤的保护作用。方法　结扎大鼠左冠脉前降支 4 0min再灌注 12 0min ,观察黄芩苷对心肌梗死后大鼠心功能、心肌梗死面积和乳酸脱氢酶 (LDH)活性、丙二醛 (MDA)含量、超氧化物歧化酶(SOD)活性等的影响。结果　结扎冠脉前 5min给黄芩苷10～ 4 0mg·kg-1能改善心肌梗死后大鼠的心功能、减少心肌梗死面积 (9%～ 30 % ) ,并能减少梗死后心肌MDA含量、提高梗死后心肌SOD、LDH的活性。结论　黄芩苷对大鼠缺血再灌注的心肌损伤有保护作用     

L-肉碱预处理对离体家兔心肌缺血再灌注损伤的保护作用

目的:观察L-肉碱预处理对离体家兔心肌缺血再灌注损伤的保护作用.方法:采用离体兔心Langendorff灌注实验模型,离体兔心24只,随机等分成3组(n=8).正常对照组:连续灌注K-H液 90 min;缺血再灌注损伤组:灌注 30 min,关闭主动脉套管停止灌注,30 min后恢复37 ℃ K-H液灌注 60 min;L-肉碱组:步骤同缺血再灌注组,但在停灌前先用含10 mmolL-1 L-肉碱的K-H液灌注 30min.记录血流动力学指标:冠脉流量(CF)、左心室舒张压(LVDP)、左心室压力时间变化率(±dp/dt);检测冠脉流出液中丙二醛(MDA)、超氧化物歧化酶(SOD)、肌酸激酶(CK)、乳酸脱氢酶(LDH)浓度和心肌组织中MDA、SOD及L-肉碱的含量.结果:L-肉碱组能显著促进再灌注时心功能恢复:±dp/dtmax和LVDP显著升高;CF增大;冠脉流出液中MDA、LDH、CK以及心肌组织中MDA浓度降低;而冠脉流出液和心肌组织中SOD含量均升高(P<0.05);心肌中L-肉碱含量明显增高(P<0.01);超微结构观察结构损伤较轻(P<0.05).结论:L-肉碱预处理具有抗兔离体心肌缺血再灌注损伤的作用.     

巴曲酶对抗狗心脏缺血/再灌损伤(英文)

目的:研究巴曲酶(Bat)对狗心脏缺血/再灌损伤的影响。方法:狗冠脉左前降枝结扎30 min后恢复血液灌注,于缺血前(Bat-Ⅰ组)或缺血后再灌前15min(Bat-Ⅱ组)静脉注射Bat(1 Bu·kg~(-1))。测定dp/dt_(max)和LVEDP及血浆CK和LDH及心肌MDA含量,观察心肌病理形态学改变。结果:I/R组动物缺血或再灌后死亡率高达65.0％,心肌损伤明显。Bat-Ⅰ和Bat-Ⅱ组动物的死亡率分别为30.0％和28.6％,P<0.05,心肌损伤减轻;血浆CK、LDH含量,LVEDP及心肌MDA含量降低; dp/dt_(max)和-dp/dt_(max)增加。结论:Bat可明显拮抗狗心脏缺血/再灌注损伤,改善心功能。     

金丝桃苷对心肌缺血与再灌注损伤的拮抗作用

目的：观察金丝桃苷（Ｈｐｙ）对缺血再灌注心肌的保护作用及双抗近氧化作用。方法：结扎家兔冠脉左降支６０ｍｉｎ后松开结扎２０ｍｉｎ，以多道生理记录仪持续记录左室内压（ＬＶＰ），左室内压变化速率（ＬＶ±ｄｐ／ｄｔ），心电图（ＥＣＧ）变化，再灌注后，取血和左心室肌测血浆肌酸磷酸激酶（ＣＰＫ），乳酸脱氢酶（ＬＤＨ）及心肌阳离子含量，采用Ｌａｎｇｅｎｄｏｒｆｆ系统，离体大鼠心脏缺血４０ｍｉｎ后再灌注３０ｍｉｎ     

莲心碱对大鼠缺血再灌注损伤心肌的保护作用

目的:研究莲心碱对大鼠缺血再灌注损伤心肌的保护作用.方法:实验大鼠24只,随机分为3组,每组8只.假手术组:冠状动脉左前降支(LAD)处穿一丝线,但不结扎;损伤对照组:结扎冠状动脉LAD,造成心肌缺血再灌注损伤;药物组:结扎冠状动脉LAD前静脉注射莲心碱5 mg&#8226;kg 1.测定每组大鼠血清中磷酸肌酸激酶(CPK)、乳酸脱氢酶(LDH)活性,丙二醛(MDA)含量,心肌梗死范围(IS).结果:与假手术组和损伤对照组比较,药物组血清CPK、LDH活性与MDA含量明显降低(P＜0.01),心肌梗死面积减少(P＜0.05).结论:莲心碱对大鼠缺血再灌注损伤心肌有保护作用.     

当归和丹参对家兔心肌缺血再灌注损伤的保护作用

目的:观察丹参、当归及当归加丹参对家兔心肌缺血再灌注损伤的保护作用.方法:结扎兔冠状动脉左室支中段,制成急性缺血再灌注模型.缺血10min时,分别iv丹参注射液、当归注射液和当归注射液加丹参注射液,观察在急性缺血及再灌注状态下心功能及血浆肌酸磷酸激酶(CPK)和丙二醛(MDA)变化.结果:丹参、当归及丹参加当归都可以使模型兔心电图Ⅱ导联∑ST段压低;LVSP,±dp/dt_(max)和增强,血浆CPK和MDA降低.结论:尽管3种治疗对心肌缺血再灌注心肌损伤都有保护作用,但当归丹参1:1配伍应用与两单位药单用比较并无统计学差异,说明中药配伍的严格性.     

红花黄素对大鼠心肌缺血-再灌注模型的作用及机制研究

目的　研究红花黄素对心肌缺血 -再灌注大鼠的影响。方法　建立大鼠冠脉结扎致心肌缺血 -再灌注损伤模型 ,观察红花黄素预防性给药对缺血大鼠血浆中肌酸磷酸激酶 (CPK)、乳酸脱氢酶 (LDH)活性及心肌和血浆中脂质过氧化物丙二醛 (MDA)含量 ,超氧化物歧化酶 (SOD)活性的影响。结果　红花黄素预防性给药能明显降低血浆CPK、LDH的活性及MDA含量 ,提高SOD的活性 ,具有明显的抗氧化性。结论　红花黄素对实验性心肌缺血 -再灌注大鼠具有明显的保护作用 ,其作用可能与其抗氧化有关     

蝙蝠葛酚性碱对心肌缺血及缺血再灌注损伤的保护作用

目的研究蝙蝠葛酚性碱(PAMD)对心肌缺血及缺血再灌注损伤的作用。方法用大鼠皮下注射异丙肾上腺素85 mg.kg-1造成心肌缺血模型,于造模前30 min灌胃给予生理盐水、PAMD(7.5,15或30 mg.kg-1)、地尔硫10 mg.kg-1或地奥心血康150 mg.kg-1,测定心肌缺血后乳酸脱氢酶(LDH)、肌酸激酶(CK)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量及病理学改变。离体大鼠心脏缺血30 min再灌注40 min,分别给予PAMD(1,10或100 mg.L-1)或地奥心血康100 mg.kg-1,测定心肌缺血再灌注后左室收缩压(LVSP)、左室舒张末压(LVEDP)和左室压最大变化速率(±dp/dtmax)、冠脉流量,测定心肌SOD活性和MDA含量。结果 PAMD显著降低缺血所致的LDH、CK和MDA升高,提高SOD活性,减轻心肌病理损伤。PAMD促进缺血再灌注末LVSP、LVEDP和±dp/dtmax等恢复,增加冠脉流量和SOD活性并降低MDA含量。结论 PAMD对心肌缺血及缺血再灌注损伤有保护作用,其机制可能与其抗氧化及改善心肌代谢有关。     

参麦注射液对正常及缺血再灌注离体豚鼠心脏的影响

目的观察参麦注射液(SM)对正常及缺血再灌注离体豚鼠心脏的影响。方法采用正常Langendorff灌流及缺血再灌注离体豚鼠心脏模型,观察SM对冠脉流量的影响,测定冠脉流出液中乳酸脱氢酶(LDH)活性及心肌组织丙二醛(MDA)、超氧化物歧化酶(SOD)的活性。结果SM可显著提高正常及缺血-再灌注离体豚鼠心脏的冠脉流量,减少缺血-再灌注后LDH的漏出总量,降低缺血再灌后心肌组织MDA的含量,升高SOD的活性。结论SM可增加正常及缺血-再灌离体豚鼠心脏冠脉流量,减轻缺血-再灌引起的心肌损伤。     

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.