中国萝芙木碱Verticillatine对麻醉狗和猫心功能与血流动力学的影响

Verticillatine(Vt)0.5～1.0mg/kg iv,能使麻醉狗的血压下降,心率减慢,cl,LVSP LV dp/dt max,LVWI,TPR降低,作用随剂量增加而加强。冠脉阻力稍降低,但心肌氧利用率和氧耗减少。颈内动脉和股动脉血流增加,阻力减少。给麻醉猫iv Vt和六羟季铵1.0 mg/kg后,BP,LVP和LV dp/dt max降低,但LV dp/dt/p和LVEDP无明显变化。说明Vt能降低心脏后负荷,对前负荷无明显影响。     

人参茎叶黄酮对狗心脏血流动力学的影响

人参茎叶黄酮20mg/kg(iv)能明显降低麻醉狗的 LVP、(dp/dt)max、TPVR、BP和耗氧量。对心脏泵功能指标 CI、SI 和心肌收缩性指标 dp/dt/CPIP 无显著影响。对反映心肌收缩敏捷度的 t-(dp/dt)max 明显延长(1～40min)。对 CO、PF 无明显影响。     

生脉注射液对麻醉动物血流动力学及心肌耗氧的影响

本文探讨华西医科大学制药厂研制的生脉注射液对心血管机能的影响。猫十只,麻醉后iv生脉注射液1ml/kg,使CO、SV、CI、LVWI、LVSP、dp/dt max和Vce-cpip显著增加,而tdp/dt max、LVET和LVEDP无明显改变。另五只猫麻醉后iv生脉注射液1ml/kg,颈动脉、股动脉、肠系膜上动脉血流量均有短暂增多。四只犬麻醉后iv生脉注射液1ml/kg,冠状动脉左旋支血流量增加,而心肌耗氧量和动静脉氧差均减少。     

川芎嗪对犬心脏血流动力学的作用

给麻醉犬静脉滴注川芎嗪1、2及4 mg/kg/min,连续10分钟;动物出现心率加快,心肌收缩力加强,血管扩张。这些作用随剂量的增加而加强。滴注1 mg/kg/min时,心率、LVP及dp/dt max增加,2 mg/kg/min时,心率、LVP、dp/dt max及冠脉血流明显增加。剂量增至4 mg/kg/min时,除上述指标明显增加外,还出现LVEDP、CI,心肌氧耗和脑血流增加,冠状动脉和脑血管阻力及总外周阻力降低。给清醒高血压犬滴注川芎嗪4 mg/kg/min及一次静注20'mg/kg也引起心率加速。心得安(ⅳ1～2 mg/kg)能对抗川芎嗪对麻醉和清醒犬的上述作用,而利血平则不能完全对抗川芎嗪的作用。     

辽吉冰凉花总甙对心功能影响的实验研究

辽吉冰凉花总甙(APAW)1.0mg/kg iv,能使麻醉家兔正常心脏的P-dP/dt环体面积(LO),LV-dP/dt_(max),Vpm及LVSP比药前增大,HR减慢。APAW和冰凉花(AAR)及毒毛旋花子甙K(SK)一样,能明显改善衰竭兔心的心功能。静脉恒速输入0.5 mg/ml APAW,25min后,心衰家兔的LVSP,LV—dP/dt max,LO均明显回升,LVEDP降低,t-dP/dt max缩短。三种强心甙的最大强心效力无显著性差异。但APAW的治疗宽度和治疗指数均较AAR和SK为大,而AAR和SK间则无显著性差异。     

辽吉冰凉花总甙对心功能影响的实验研究

辽吉冰凉花总甙(APAW)1.0mg/kg iv,能使麻醉家兔正常心脏的P-dP/dt环体面积(LO),LV-dP/dt_max,Vpm及LVSP比药前增大,HR减慢。APAW和冰凉花(AAR)及毒毛旋花子甙K(SK)一样,能明显改善衰竭兔心的心功能。静脉恒速输入0.5 mg/ml APAW,25min后,心衰家兔的LVSP,LV—dP/dt max,LO均明显回升,LVEDP降低,t-dP/dt max缩短。三种强心甙的最大强心效力无显著性差异。但APAW的治疗宽度和治疗指数均较AAR和SK为大,而AAR和SK间则无显著性差异。     

硅酸钠对犬血流动力学的作用

麻醉犬8只,iv硅酸钠10～20mg/kg,观察血流动力学各参数的影响。结果表明Na_2SiO_3可使LVSP,+dp/dt max和VCE-+dp/dtmax增加,-dp/dt max增加而T值缩短,可使SBP,DBP和MAP增加,CI增加而对HR及THR影响不大。认为升压作用与CI增加,心脏作功增加有关。     

甲基莲心碱对正常及高血压大鼠血流动力学的影响

iv甲基莲心碱(Nef)6 mg/kg于正常血压、肾性高血压、DOCA盐型高血压大鼠,在血压下降的同时,伴有LVSP,±(dp/dt)max,(dp/dt)P~(-1)的降低,正常血压及肾性高血压大鼠LVSP~-(dp/dt)P~(-1)环缩小,其斜率变小,心率短时变慢,LVEDP变化不明显。iv Nef 2 mg/kg于Wistar高血压大鼠时,仅明显降低血压,而对其它血流动力学指标无明显影响,Nef降低舒张压的作用大于降低收缩压。猫后肢灌流实验证明Nef有明显降低血管阻力的作用。结果表明Nef的降压作用可能由于扩张外周血管所致。     

左旋四氢巴马汀对麻醉大鼠血流动力学影响

L-THP 6mg/kg iv仅显著降低麻醉大鼠血压,LVP-过性降低。iv L-THP 18mg/kg在显著降低血压的同时伴有LVP,±(dP/dt)_(max),(dP/dt)P~(-1)降低及HR减慢。但血压下降程度比心室收缩性能下降为大。L-THP依剂量降低DAP,且降低程度大于SAP。表明L-THP能降低外周阻力,大剂量时对心脏收缩性能有抑制作用。     

心喘灵(XC-1)及其衍生物XC-2对麻醉犬血流动力学的作用

本工作比较研究了心喘灵(XC-1)及其衍生物XC-2(8204) 对麻醉开胸犬心脏血流动力学的作用。用递加剂量法静注心喘灵0.5,1.0,2.0和4.0 mg/kg,每二个剂量之间的间隔为5 min,给药后MAP和LVP下降,HR减慢,CI和SI增加,TPR降低,冠状、颈内和股动脉血流增加,血管阻力下降,±LVdp/dt max增加,而LV dp/dt/p改变不明显,LVW,CVP和MVO₂无明显变化。用同法静注同样剂量XC-2的作用和心喘灵相似,但较弱;一次静注5 mg/kg也出现柑似但较弱的作用。它们的作用是通过阻断α和β受体及直接扩张血管所引起。     

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.