维拉帕米防治缺血和缺血／再灌注性室颤的探讨

目的：探讨维拉帕米抗缺血及缺血／再灌注性室颤的机理。方法：用高效液相色谱－电化学法测定豚鼠离体心灌注液中去甲肾上腺素（NE）含量。结果：维拉帕米组在灌止灌注时心脏NE释放明显低于对照组（P＜0．01）,缺血及缺血／再灌注性室颤发生率维拉帕米组显著低于对照组（P＜0．01）。结论：维拉帕米抑制缺血心肌NE释放为其抗缺血及缺血／再灌注室颤的机理之一。     

维拉帕米防治缺血和缺血/再灌注性室颤的探讨

目的 :探讨维拉帕米抗缺血及缺血 /再灌注性室颤的机理。方法 :用高效液相色谱—电化学法测定豚鼠离体心灌注液中去甲肾上腺素 (NE)含量。结果 :维拉帕米组在灌止灌注时心脏NE释放量明显低于对照组 (P <0 0 1) ,缺血及缺血 /再灌注性室颤发生率维拉帕米组显著低于对照组 (P <0 0 1)。结论 :维拉帕米抑制缺血心肌NE释放为其抗缺血及缺血 /再灌注室颤的机理之一。     

蝙蝠葛碱对心肌去甲肾上腺素出胞释放的影响

目的研究蝙蝠葛碱对心肌去甲肾上腺素（ＮＥ）出胞释放的药理作用。方法用高压液相色谱—电化学法测定电刺激时豚鼠离体灌注心脏流出液的ＮＥ含量。结果不加实验条件时第１次电刺激（Ｓ１）与第２次电刺激（Ｓ２）所引起的ＮＥ释放量无差别（Ｐ＞０．０５），蝙蝠葛碱（３０μｍｏｌＬ－１）、维拉帕米（５μｍｏｌＬ－１）明显减少Ｓ２引起的ＮＥ释放（Ｐ＜０．０１，Ｐ＜０．０５）；组间比较，蝙蝠葛碱组、维拉帕米组均显著低于对照组（Ｐ＜０．０１），而蝙蝠葛碱组与维拉帕米组之间无统计学差别（Ｐ＞０．０５）。结论蝙蝠葛碱具有抑制心肌去甲肾上腺素出胞释放的作用。     

蝙蝠葛碱抑制射频消融术后对病人血小板膜糖蛋白IV再分布的作用

目的：探讨蝙蝠葛碱对射频消融术（RFCA）后病人血小板不可逆性聚集的影响。方法：运用流式细胞术测定14例阵发性上性心动过速病人RFCA术前后静息血小板和凝血酶活化血小板膜糖蛋白IV（GPIV）及凝血酶敏感蛋白（TSP）的分布，结果：RFCA术后静息血小板膜GPiV分布明显高于术前（P＜0．01），凝血酶活化的血小板膜GPiV及TSP分布，RFCA术后明显高于术前（P＜0．05或P＜0．01），蝙蝠葛碱可显著抑制FCA术后由凝血酶诱导的血小板膜GPIV再分布（P＜0．05或P＜0．01），部分抑制凝血酶诱导的α－颗粒内TSP的释放（P＜0．05），结论：蝙蝠葛碱可抑制RFCA后血小板的不可逆性聚集。     

雷米普利对糖尿病大鼠心脏的药理性预适应作用

目的：评价雷米普利对糖尿病大鼠心脏的药理性预适应作用。材料和方法：大鼠尾静脉注射链脲菌素（45mg／kg）制备糖尿病模型。随机分为4组：缺血／再灌注（I／R）组，缺血预适应（IP）组，雷米普利（RAM）药理性预适应组，雷米普利＋缺血预适应（RAM＋IP）组。RAM组及RAM＋IP组每天用雷米普利（1mg／kg）灌胃，共4周。4周后全部大鼠行心肌30min缺血继之2h再灌注，IP组及RAM＋IP组于30min缺血前行心肌缺血预适应。连续监测ST-段变化以及缺血期室性心律失常发生情况，TTC染色测定心肌梗死范围，TUNEL法检测心肌细胞凋亡，免疫组化法测定Bcl-2与Bax的表达，光、电镜下观察心肌形态学改变。结果：与I／R组比较，IP及RAM组均见缺血心脏ST-段抬高幅度显著降低（P〈0．05），室早出现时间推迟（P〈0．05），持续时间缩短（P〈0．05），室速、室颤发生率降低（P〈0．05），心肌梗死范围缩小（P〈0．01），心肌细胞凋亡减轻（P〈0．001），Bcl-2／Bax比值升高（P〈0．05），形态学观察见心肌损伤减轻；RAM＋IP组可见室早持续时间缩短（P〈0．05），室速、室颤发生率降低（P〈0．05），心肌梗死范围缩小（P〈0．01），心肌细胞凋亡减轻（P〈0．001），Bcl-2／Bax比值升高（P〈0．05）。与IP组比较，RAM＋IP组上述各指标无明显差异。结论：IP对患糖尿病4周的大鼠具有心脏保护效应，长期服用RAM对糖尿病心肌具有药物预适应作用，均可增强糖尿病大鼠心脏对缺血／再灌注损伤的耐受性，但二者联用无协同效应。     

蝙蝠葛碱对心肌去甲肾上腺腺出胞释放的影响

目的 研究蝙蝠葛碱对心肌去甲肾上腺素（ＮＥ）出胞释放的药理作用，方法 用高压液相色谱－电化学法测定电刺激时豚鼠离体灌注心脏流出液的ＮＥ含量，结果 不加实验条件时第１次电刺激（Ｓ１）与第２次电刺激（Ｓ２）所引起的ＮＥ释放量无差别（Ｐ〉０．０５），蝙蝠葛碱（３０μｍｏｌ．Ｌ＾－１）维持帕米（５μｍｏｌ．Ｌ＾－１）明显减少Ｓ２引起的ＮＥ释放（Ｐ〈０．０１，Ｐ〈０．０５），组间比较，蝙蝠葛碱组，维拉帕米组     

蝙蝠葛酚性碱抗兔心脑缺血再灌注损伤作用

目的：探讨蝙蝠葛酚性碱抗家兔心脑缺血再灌注损伤的作用及其机制。方法：结扎家兔左冠状动脉前降支及双侧颈总动脉,30min后复灌,制成心脑缺血再灌模型。分别于缺血前10min,缺血2、10、30min,再灌1、10、30、60、120、180、240min时经股动脉取血2mL,再灌240min后立即取出左心室、海马、皮层、小脑。测定血清及各组织中内二醛（MDA)含量和超氧化物歧化酶（SOD）活性。结果：与对照组相比,缺血再灌组（I－R）复灌10min后血清MDA含量显著升高,而SOD活性显著降低（P＜0．05）。与I－R组相比,应用RAMd后,血清MDA含量降低,而SOD活性升高（P＜0．05）。各组织中MDA含量与SOD活性变化与血清中相似。结论：蝙蝠葛酚性碱通过减轻脂质过氧化所造成的损伤及提高SOD活性,对心脑缺血再灌注损伤具有一定的保护作用。     

心房肽Ⅲ对离体大鼠心脏缺血再灌注损伤的保护作用

目的观察心房肽Ⅲ（APⅢ）对离体大鼠心肌缺血再灌注的保护作用。方法离体心脏停灌30min,造成全心缺血,复灌60min。共取36个心脏随机分为6个组：高、中、低（1×10^-8mol／L、3×10^-8mol／L、1×10^-8mol／L）3个剂量APⅢ组,（缺血再灌注）模型对照组,维拉帕米（10^-7mol／L）对照组和正常对照组。测定复灌第20分钟冠脉流出液中乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）的活性和灌流结束后心肌组织SOD活性和MDA含量。结果灌流液中,3种剂量的APⅢ组和维拉帕米组,SOD活性均显著高于模型对照组（P〈0．05）,LDH活性均低于模型对照组,但无统计学意义（P〉0．05）。心肌组织中,各剂量APⅢ组和维拉帕米组的SOD活性均高于模型对照组（P〈0．01）;各剂量APⅢ组和维拉帕米组MDA的含量均低于模型对照组,高、中剂量APⅢ组（P〈0．05）,而低剂量APⅢ组和维拉帕米组差异无统计学意义（P〉0．05）。结论APⅢ可以减少心脏I／R中氧自由基的生成,保护心肌,作用优于维拉帕米,并有剂量依赖性。     

脑利钠肽后处理对高血脂大鼠缺血／再灌注心肌的保护作用

目的观察脑利钠肽后处理对高血脂大鼠缺血／再灌注心肌的保护作用。方法高血脂SD大鼠24只,随机分为3组：假手术组、缺血／再灌注组、脑利钠肽后处理组,每组8只。制备大鼠心肌缺血／再灌注模型。测定血清肌酸激酶（CK）、超氧化物岐化酶（SOD）、丙二醛（MDA）含量和心肌梗死范围。结果再灌注结束后,脑利钠肽后处理组和缺血／再灌注组CK明显高于假手术组[分别为（758．11±39．94）,（815．19±40．85）,（219．17±22．63）U／L,P〈0．01],脑利钠肽后处理组CK低于缺血／再灌注组（P〈0．05）。脑利钠肽后处理组血清中SOD含量高于缺血／再灌注组,MDA含量低于缺血／再灌注组（P〈0．05）。脑利钠肽后处理组坏死区与缺血区比值低于缺血／再灌注组[分别为（33．0±5．2）％,（38．4±3．1）％,P〈0．05]。结论脑利钠肽后处理对高血脂大鼠缺血／再灌注心肌具有保护作用。     

异丙酚对大鼠离体心脏再灌注心律失常的影响

目的：实验观察异丙酚对大鼠离体心脏再灌注心律失常的影响。方法：SD大鼠Langendorff离体心脏灌注后,建立冠状动脉左前降支局部心肌缺血和再灌注心律失常模型。分6组：对照组;异丙酚1μg/ml组;异丙酚3μg/ml组;维拉帕米10ng/ml组;异丙酚1μg/ml加维拉帕米10ng/ml组;异丙酚3μg/ml加维拉帕米10ng/ml组。定时测量冠脉流量、心率和连续监测ECG,以比较各组再灌注期室性期前收缩（VPB）、心室纤颤（VF）、室性心动过速（VT）的发生率以及正常窦性节律（NSR）的持续时间。结果：与对照组相比,后4组再灌注期的VF发生率均有非常显著地降低（P＜0．01）,VF的持续时间显著缩短（P＜0．01）,NSR的时间明显延长,而VT的发生率仅有下降趋势。结论：3μg/ml的异丙酚与10ng/ml的维拉帕米相似,对大鼠离体心脏再灌注期VF的发生率和持续时间具有非常显著的抑制作用。     

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.