卡维地洛对大鼠缺血再灌注心肌超微结构的影响

目的:评价第三代β受体阻断药——卡维地洛(CVD)对大鼠在体心脏缺血再灌注心肌的超微结构的影响.方法:实验大鼠24只,假手术组8只,只开胸,不结扎左前降支冠状动脉,另外16只通过结扎左前降支冠状动脉,建立大鼠在体心脏缺血再灌注损伤模型.后者又分为对照组8只,未给药;CVD组8只,术前7 d连续胃管给CVD(1 mg•kg 1•d 1),结扎左前降支冠状动脉30 min后松开进行再灌注6 h,处死动物.观察乳酸脱氢酶(LDH)、肌酸磷酸酶(CK MB)、过氧化物酶(MDA)变化并对心肌进行HE染色及电镜检查.结果: CVD减少CK MB、LDH及MDA的释放.对照组心肌细胞HE染色及电镜检查呈明显片状或局灶性坏死,润盘结构紊乱,大量反应性的中性粒细胞浸润于坏死细胞之间;CVD组心肌细胞损伤程度明显减轻,粒细胞浸润也明显减少, 润盘结构基本正常.结论:CVD对大鼠在体缺血再灌注心脏具有明显保护作用.CVD有抗氧化、减少心肌梗死区中性粒细胞浸润、减少心肌损伤等多种作用.     

血栓通预处理对大鼠心肌缺血再灌注损伤的影响

目的:研究血栓通对大鼠缺血心肌的保护作用。方法:选用40只Wister大鼠分为正常对照组、模型组、血栓通组及维拉帕米组,采用结扎大鼠冠状动脉左前降支建立出大鼠心肌缺血再灌注损伤模型。检测大鼠血清磷酸肌酸激酶(CPK)、乳酸脱氢酶(LDH)、血清及心肌组织超氧化物歧化酶(SOD)和脂质过氧化物丙二醛(MDA),研究血栓通对心肌梗死范围的影响。结果:血栓通可对抗结扎大鼠冠状动脉左前降支所致的大鼠急性心肌损伤,使心肌缺血大鼠的CPK及LDH降低,并可增加心肌组织SOD的活性,减少MDA生成且能显著缩小心肌梗死的范围。结论:血栓通对大鼠心肌缺血有保护作用,其机制可能与抗脂质过氧化反应有关。     

银杏内酯对结扎大鼠冠状动脉致心肌缺血的影响

目的:研究银杏内酯对大鼠心肌缺血的保护作用.方法:大鼠按体重分为7组,分别为银杏内酯10,20,40mg·kg-1组,银杏叶提取物150mg·kg-1组,普萘洛尔5mg·kg-1组,模型组和正常组.采用结扎冠状动脉左前降支造成心肌梗死模型,分别测定手术后各组大鼠的心肌损伤范围(坏死及缺血范围),血清磷酸肌酸激酶(CPK)、乳酸脱氢酶(LDH)活性及心肌组织中丙二醛(MDA)含量.结果:银杏内酯(10,20,40mg·kg-1)能明显减轻心肌损伤,降低心肌缺血大鼠血清中LDH和CPK活力及MDA含量.结论:银杏内酯对结扎大鼠冠状动脉所致心肌缺血损伤具有明显的保护作用.     

尼可地尔对大鼠缺血再灌注心肌梗死的影响

目的 观察不同剂量尼可地尔对大鼠缺血再灌注心肌梗死的影响.方法 Wistar大鼠100只,随机分为五组:尼可地尔低剂量组、尼可地尔中剂量组、尼可地尔高剂量组、假手术组和对照组.麻醉大鼠,结扎左冠状动脉前降支60 min,再灌注60 min,从心肌梗死面积(MIS),血清酶学,丙二醛(MDA)、超氧化物歧化酶(SOD)的变化观察尼可地尔的抗心肌缺血再灌注损伤作用.结果 与对照组比较,尼可地尔中高剂量组可降低心肌梗死面积,降低血清肌酸磷酸激酶(CK)和乳酸脱氢酶(LDH)活性,提高心肌SOD活性,减少心肌MDA含量(P＜0.01).结论 在一定剂量范围内,尼可地尔可降低心肌梗死面积,对急性缺血心肌有保护作用.     

雌激素对骨骼肌缺血再灌注损伤的保护作用

目的:探讨17β-雌二醇对大鼠骨骼肌缺血再灌注损伤的作用.方法:制作右后肢缺血再灌注模型,30只大鼠随机分为3组,假手术组;缺血再灌注对照组:骨骼肌缺血冉灌注+生理盐水;雌激素干预组:骨骼肌缺血再灌注+雌激素干预.用全自动牛化分析仪测定血浆肌酸磷酸激酶(CPK)、乳酸脱氢酶(LDH),用硫代巴比妥酸比色法测定丙二醛(MDA),用比色法测定小腿三头肌组织中髓过氧化酶(MPO)活性;高倍显微镜观察小腿三头肌组织结构变化.结果:缺血再灌注对照组、雌激素十预组与假手术组比较,血浆CPK、LDH、MDA及MPO含量明显升高(P<0.01),雌激素干预组与缺血再灌注对照组相比血浆CPK、LDH、MDA及MPO含量明硅降低(P<0.01);缺血冉灌注对照组、雌激素干预组均可见骨骼肌损伤,缺血再灌注对照组明显重于雌激素干预组.结论:雌激素对肢体骨骼肌缺血再灌注损伤具有保护作用,其作用与抑制中性粒细胞的效应有关.     

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.     

冠心宁注射液对大鼠心肌缺血再灌注损伤的保护作用

目的:观察冠心宁注射液对大鼠心肌缺血再灌注损伤的保护作用,探讨冠心宁抗心肌缺血再灌注损伤的保护机理.方法:雄性SD大鼠30只随机分成假手术组(C组)、缺血再灌注组(I/R组)、冠心宁治疗组(G组),建立大鼠在体心肌缺血再灌注模型:C组丝线穿过冠状动脉前降支但不结扎,I/R、G组通过结扎心脏左冠状动脉前降支40 min,再灌注60 min制作缺血再灌注损伤动物模型.缺血前30 min,G组经腹腔注射冠心宁注射液10.0 ml·kg-1,余两组注射等量0.9%氯化钠注射液.测定再灌注60 min后心肌超氧化物岐化酶(SOD)活性及丙二醛(MDA)含量,同时取每组大鼠心肌检测梗死面积,电镜下观察缺血区心肌超微结构变化.结果:与I/R组相比,G组再灌注后60 min心肌MDA含量降低(P<0.01),SOD活性增高(P<0.01),梗死面积较小(P<0.01),心肌超微结构受损较轻.结论:冠心宁注射液对心肌缺血再灌注损伤有明显的保护作用,其机制与其增强心肌抗氧化作用有关.     

异可利定对大鼠心肌缺血及缺血/再灌注所致心律失常的影响

目的探究异可利定对大鼠心肌缺血及缺血/再灌注所致心律失常的影响。方法将SD大鼠随机分为假手术组、心肌缺血/再灌注模型组、阳性药维拉帕米组、异可利定(2.5、5、10 mg·kg~(-1))组,共6组,每组16只。结扎大鼠左冠状动脉建立大鼠心肌缺血/再灌注损伤模型,记录Ⅱ导联心电图,并测定大鼠心肌缺血面积、心肌梗死范围及心肌组织超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)等生化指标。结果异可利定可以明显降低大鼠缺血/再灌注室性早搏(ventricular extrasystole,VE)、室性心动过速(ventricular tachycardia,VT)、心室颤动(ventricular fibrillation,VF)的发生率;减少缺血期间大鼠心肌缺血面积和心肌梗死范围;明显升高缺血/再灌注损伤心肌SOD、GSH-Px的含量,降低MDA含量。结论异可利定对心脏缺血/再灌注损伤有保护作用,可能与其抗氧化作用有关。     

玉郎伞黄酮对心肌缺血再灌注损伤的保护作用

目的探讨玉郎伞黄酮(YF)对大鼠心肌缺血再灌注损伤(MIRI)的保护作用.方法60只健康SD大鼠,随机分为假手术(Sham)组、缺血再灌注损伤(MIRI)对照组、溶剂生理盐水(NS)组和3个预处理组(YF低、中、高剂量组,各组大鼠♀♂各半).结扎冠状动脉左前降支30min后,再灌注60min,建立MIRI模型.用不同剂量YF在结扎冠状动脉左前降支前30min分别做预处理.再灌注结束后采血,测定血浆中谷草转氨酶(AST)、乳酸脱氢酶(IDH)、乳酸脱氢酶同工酶1(LDHl)、超氧化物岐化酶(SOD)和丙二醛(MDA)的改变,测量心肌梗死范围.结果与MIRI组比较,YF预处理能明显降低血浆中AST、LDH、LDHl和MDA含量,能提高SOD活性,降低心肌梗死范围.结论YF对大鼠心肌MIRI具有显著的保护作用.     

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     

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.