羟苯氨酮对实验性心肌缺血的治疗作用

目的研究强心扩血管新药羟苯氨酮(oxyphenamone)对心肌缺血的治疗作用。方法用多导生理记录仪和电磁流量计测定心脏血流动力学参数，观察药物对阻断冠脉致急性心肌梗死猫心脏生理功能的影响。形成异丙肾上腺素致大鼠心肌缺血坏死模型，从心肌酶学及病理形态学方面评价药效。结果羟苯氨酮(2-8 mg·kg^-1,iv)可剂量依赖性地降低心梗猫的心率、血压、血管阻力与张力时间指数(TTI)，轻度增加心肌收缩力与心输出量，不影响左室压与心脏作功。羟苯氨酮(4-8 mg·kg^-1,ip)可明显减轻异丙肾上腺素致大鼠心肌肌酸磷酸激酶(CPK)、丙二醛(MDA)与血清谷草转氨酶(GOT)活性变化与病理形态学损伤。结论羟苯氨酮对心肌缺血性损伤有明显治疗作用。     

强心扩血管药羟苯氨酮对大鼠,猫和狗心脏血流动力学的影响

为了解强心扩血管新药羟苯氨酮( oxyphenamone,9003 )对在体心血管系统的效应,用多导生理仪与电磁流量计测定大鼠,猫与狗的心脏血流动力学参数。结果表明,静注羟苯氨酮引起血压与血管阻力中度下降,心输出量,心肌收缩力与收缩力变化速度,冠状动脉和股动脉血流量明显增加。羟苯氨酮对心率与左室压的影响呈现种系差别,它增加狗的左室收缩压与压力变化速度,降低左室舒张末期压力,小剂量羟苯氨酮(1或3mg·kg^-1)引起狗的心率轻度降低,剂量增到6mg·kg^-1,心率中度加快。羟苯氨酮不影响猫的心率与左室压。大鼠静注羟苯氨酮后引起心率,左室收缩压与压力变化速度降低,左室舒张末期压力无变化。羟苯氨酮对心脏血流动力学的影响有待用病理模型作进一步观察。     

强心扩血管药羟苯氨酮对离体心肌与血管的作用

为阐明强心扩血管药羟苯氨酮对心肌与血管的直接影响,采用离体心脏,离体心肌与血管制备,以心肌张力、心率、冠脉流量及血管平滑肌张力为观察指标。结果显示:给离体大鼠心脏灌流羟苯氨酮0.1～1μmol·L^-1可使心肌收缩力和冠脉流量明显增加,心率轻度减慢。羟苯氨酮剂量依赖性地增加豚鼠乳头肌和左房肌张力,并减慢右房频率。羟苯氨酮(1～50μmol·L^-1)非竞争性地对抗KCl,5-HT和CaCl₂致狗冠状动脉,基底动脉和肠系膜动脉的收缩,显示它有松弛血管平滑肌的作用。与磷酸二酯酶抑制剂类药物米力农作比较,两者的正性肌力作用与扩血管作用相似。然而,羟苯氨酮减慢心搏频率,米力农则增加心率。提示羟苯氨酮有直接正性肌力、负性频率与扩血管作用。     

羟苯氨酮对戊巴比妥钠致心力衰竭的治疗作用

目的：研究强心扩血管新药羟苯氨酮(oxyphenamone) 对心力衰竭的治疗作用。 方法：用多导生理仪与电磁流量计测定戊巴比妥钠致心力衰竭豚鼠、 猫与狗的心脏血流动力学参数。 结果：iv 羟苯氨酮1～8 mg.kg^-1, 剂量依赖性地增加心肌收缩力、 左室收缩压、 心输出量、 心脏作功及冠状动脉血流量, 其作用强度与磷酸二酯酶抑制剂(PDEI)氨力农(amrinone) 相似。 而PDEI增加心率, 易致心律失常, 并继续降低血压; 羟苯氨酮则减慢心率, 使降低的血压上升。 结论：羟苯氨酮能明显改善心衰动物的心脏功能,其作用优于PDEI, 有可能发展成为治疗心力衰竭的新药。     

羟苯氨酮对离体鼠心停灌-复灌损伤的保护作用

目的研究羟苯氨酮对全心停灌-复灌损伤的影响。方法采用离体大鼠心脏停灌40 min-复灌30 min模型，从心脏功能、心肌能量代谢、抗氧化、线粒体钙超载及超微结构等方面观察药物作用。结果停灌前和复灌时给予羟苯氨酮(1~10 μmol·L^-1)明显增加复灌时心肌收缩力与冠脉流量，降低冠脉流出液的肌酸磷酸激酶(CPK)活性，对抗损伤所致的心肌三磷酸腺苷(ATP)与磷酸肌酸(PCr)含量降低，增强心肌抗氧化能力，对抗线粒体钙超载，使线粒体超微结构保持得比较完整。结论羟苯氨酮明显对抗停灌-复灌致心肌损伤，为该药保护再灌注损伤提出有力依据。     

羟苯氨酮保护大鼠心脏对抗心肌缺血-再灌注损伤

目的研究强心扩血管新药羟苯氨酮(oxyphenamone)对心肌缺血-再灌注损伤的保护作用。方法对离体或在体大鼠心脏，阻断冠脉前降支10 min后行再灌注15 min(离体)或30 min(在体)，形成心肌缺血-再灌注损伤模型，从心电图、心肌酶学与心肌超微结构等方面观察药效。结果羟苯氨酮(离体心脏灌流1-10 μmol·L^-1，或静脉注射0.1-1.0 mg·kg^-1)剂量依赖性地明显减少再灌注时的心律失常，对抗损伤所致心肌CPK，LDH与MDA的变化，减轻心肌超微结构损伤。结论羟苯氨酮明显保护离体和在体大鼠心肌对抗冠脉阻断所致缺血-再灌注损伤。     

芍药苷对正常麻醉开胸犬血流动力学及心肌耗氧量的影响

目的:观察芍药苷对正常麻醉开胸犬血流动力学及心肌耗氧量的影响。方法:经十二指肠给药,以血压、左室内压、左室作功、冠脉阻力、心肌耗氧量等为观测指标,研究芍药苷对犬血流动力学及心肌耗氧量的影响。结果:芍药苷具有降低左室内压,降低左室作功指数、降低血压、降低总外周阻力、降低冠脉阻力;降低心肌耗氧量的作用。结论:芍药苷可通过增加冠脉流量,增加氧的供应,降低心肌耗氧量,改善心脏血流动力学。     

三甲氧苄嗪

【化学名】 1-(2,3,4-三甲氧苄基)哌嗪二盐酸盐【结构式】【作用特点】本品为作用较强的抗心绞痛药物,能减低心脏工作负荷,降低心肌耗氧和能量的消耗,从而改善心肌氧的供需平衡;促进心肌代谢及心肌能量的产生;它能对抗肾上腺素、去甲肾上腺素及加压素的作用,直接作用于血管平滑肌,降低血管壁阻力,增加冠脉血流量及周围循环血流量;促进侧枝循环的形成和发展,从而使动脉阻塞区心肌血流恢复,保护心肌,对心肌细胞膜具有特殊作     

葛根素对急性心肌缺血狗区域性心肌血流与心脏血流动力学的作用

麻醉开胸狗ⅳ葛根素(puerarin)可减慢心率(HR)、降低主动脉压(MAP),用同位素标记微球法测得的缺血区侧枝冠脉血流量并不减少。从狗的右室旁路制备的心脏血流动力学实验发现葛根素明显减低张力一时间指数(TTI)与左室压力升高速度(LV dp/dt)。当MAP调整到给药前的水平时,TTI与LV dp/dt恢复,进入缺血区的侧技血流增加,非缺血区的冠脉血流量(CBF)亦增加。葛根素减低冠脉血管阻力(CVR)的作用比减低全身血管阻力(SVR)的作用更显著。葛根素不影响心肌收缩力,但增加局部心肌缺血时的侧枝血流并减少与心肌氧消耗有关的血流动力学参数。这些结果提示葛根素有益于治疗心肌缺血。     

生脉输液对麻醉犬血流动力学及心肌耗氧量的影响

目的研究生脉输液对麻醉犬血流动力学及心肌耗氧量的影响。方法将杂种犬36只,随机分为6组(每组6只):对照组、阳性药组(硝酸甘油注射液组和生脉注射液组)、生脉输液高、中、低三个剂量组。人工呼吸下开胸,观察用药前后不同时间点麻醉犬的冠脉流量(CBF)、心输出量(CO)、冠脉阻力(CAVR)、总外周阻力(TPVR)、心搏出量(SV)、心搏指数(SI)、心脏指数(CI)、左室作功(LVSW)、心肌血流量(MBF)、心肌耗氧指数(MOCI)、耗氧量(VO2)、心肌氧利用率(MOUR)等指标的变化。结果与对照组比较,生脉输液(200,100 mg生药.kg-1)能显著增加麻醉犬冠状动脉和主动脉的血流量、增加心肌血流量,降低总外周血管阻力和冠状动脉阻力,提高心搏出量和心肌氧利用率。结论生脉输液对麻醉犬血流动力学参数有改善作用,具有良好的抗心肌缺血作用。     

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.