莲心碱衍生物抗实验性心律失常的作用

目的:研究4种莲心碱衍生物抗心律失常的药理作用.方法:采用哇巴因、氯化钙、乌头碱3种抗心律失常模型.结果:4种莲心碱衍生物(5 mg•kg 1,iv)均能显著提高哇巴因致豚鼠、乌头碱致大鼠发生室性期前收缩(VE)、室性心动过速(VT)、心室纤颤(VF)及心脏停搏(CA)的用量,延长CaCl2诱发大鼠心律失常的出现时间,缩短生存大鼠的窦性心律恢复时间,减少死亡率.结论:4种莲心碱衍生物均有广泛的抗心律失常作用.     

二苯甲酰莲心碱抗实验性心律失常的作用

目的：研究二苯甲酰莲心碱抗实验性心律失常的作用。方法：采用乌头碱、哇巴因、氯化钙3种抗心律失常模型。结果：二苯甲酰莲心碱5mg.kg^1可明显提高乌头碱所致大鼠，哇巴因致豚鼠发生室性早搏，室性心动过速，室颤及心脏停搏用量，延长氯化钙诱发大鼠出现心律失常的时间，缩短窦律恢复时间，提高窦律恢复律，延长死亡时间及降低死亡率，结论：二苯甲酰莲心碱具有广泛的抗心律失常作用。     

二对氯苯甲酰莲心碱对实验性心律失常的影响

目的　研究二对氯苯甲酰莲心碱抗心律失常的药理作用。方法　采用乌头碱、哇巴因、氯化钙 3种抗心律失常模型。结果　二对氯苯甲酰莲心碱 5mg·kg-1iv可明显提高乌头碱致大鼠、哇巴因致豚鼠发生室性早搏、室性心动过速、室颤及心脏停搏用量 ;延长氯化钙诱发大鼠心律失常的出现时间 ,减少早搏、室颤的发生率及死亡率。结论　二对氯苯甲酰莲心碱具有广泛的抗心律失常作用     

二乙酰基莲心碱抗实验性心律失常的作用

目的研究二乙酰基莲心碱抗心律失常的药理作用.方法采用乌头碱、哇巴因、氯化钙3种抗心律失常模型.结果二乙酰基莲心碱5mg     

四氢小蘖碱的抗心律失常作用

四氢小蘖碱(THB,30mg/kg ip)能明显对抗大鼠氯化钙或氯化钡所诱发的心律失常。THB(40mg/kg ip)对大鼠缺血—再灌性心律失常有保护作用,使其室颤(VF)发生率减低,窦性心律恢复时间缩短及死亡率显著降低。THB(10mg/kg iv)也明显减少电刺激兔下丘脑诱发的室性心律失常发生率。能提高哇巴因诱发的室性早搏、室性心动过速、室颤和心脏停搏的用量,但统计学尚不显著。对乌头碱诱发的心律失常无对抗作用。THB(30mg/kg ip)相当1/17LD_(50))对大鼠血液动力学指标仅有轻度抑制作用。表明THB抗心律失常有效剂量无明显不良影响。     

葛根素磺酸钠与葛根素抗心律失常作用的比较

目的:探讨葛根素磺酸钠的抗心律失常作用。方法:用氯仿、乌头碱、哇巴因3种方法建立心律失常模型,比较葛根素磺酸钠与葛根素抗心律失常的作用。结果:葛根素磺酸钠和葛根素均能降低氯仿致KM小鼠心室纤颤的发生率,明显提高乌头碱致SD大鼠室性期前收缩、室性心动过速、室颤、心搏停止的阈剂量,明显提高哇巴因致EWG/B豚鼠室性期前收缩、室性心动过速、室颤、心搏停止的阈剂量,但葛根素磺酸钠的效果更好。结论:葛根素磺酸钠具有较好的抗心律失常的作用,为其临床治疗心律失常奠定基础。     

阿魏酸钠抗心律失常机制的初步探讨

目的探讨阿魏酸钠是否具有抗心律失常作用及其可能的抗心律失常机制。方法应用哇巴因及乌头碱建立心律失常的动物模型 ,并观察阿魏酸钠对心律失常的影响。结果阿魏酸钠0 6g/kg静脉推注可对抗哇巴因诱发的室性心律失常 ,使室性早搏、室性心动过速、室颤的发生时间延长 ,并可提高哇巴因致室性早搏、室性心动过速、室颤的剂量 ,两组之间差异有显著意义 (P <0 0 1) ,但阿魏酸钠不能对抗乌头碱诱发的心律失常。结论阿魏酸钠具有对抗哇巴因诱发的心律失常作用 ,机制可能与其对钾离子通道的阻滞作用有关     

甲基莲心碱对大鼠血压、血小板聚集和血栓形成的影响

采用比浊法研究甲基莲心碱对大鼠血压及血小板聚集、血栓形成的影响，结果显示甲基莲心碱在降低血压的同时，能剂量依赖性地抑制ＡＤＰ和胶原诱导的正常大鼠、肾性高血压大鼠和高脂喂养大鼠血小板聚集；甲基莲心碱亦能明显延长电刺激大鼠颈动脉闭塞性血栓形成时间。此结果表明甲基莲心碱具有降压与抗血小板聚集和血栓形成的双重作用。     

槐果碱对哇巴因诱发豚鼠室性心律失常的影响

目的观察槐果碱的抗室性心律失常作用。方法将哇巴因诱发的室性心律失常豚鼠,分为对照组与不同剂量槐果碱组(5、2.5和1.25 mg·kg~(-1))。通过心电图仪连续观察记录室性早搏(室早)、室性心动过速(室速)、室扑、室颤及心脏停搏出现时间,计算哇巴因的累积量。结果槐果碱各组与对照组相比,仅5 mg·kg~(-1)组能增加出现室早、室速、室扑、室颤及心脏停搏的哇巴因累积量(P<0.01)。结论槐果碱对哇巴因诱发的豚鼠室性心律失常有一定的抑制作用,以5 mg·kg~(-1)的剂量为佳。     

毛果芸香碱对实验性心律失常的保护作用

目的：观察毛果芸香碱对实验性心率失常的影响。方法：分别以乌头碱，氯化钡和哇巴因制备实验性动物心律失常模型，观察毛果芸香碱的干预作用。结果：毛果芸香碱可显著延迟乌头碱引起的大鼠室性心律失常的出现（P〈0．05），延长出现心律失常后的存活时间（P〈0．05）；能明显延迟氯化钡引起的大鼠双相室性心律失常的出现（P〈0．01），缩短心律失常的持续时间（P〈0．01）；能显著延长哇巴因引起豚鼠出现心律失常后的存活时间（P〈0．05）。毛果芸香碱的上述作用可被M3受体阻断荆4-DAMP完全逆转。结论：毛果芸香碱具有对抗乌头碱和氯化钡诱发大鼠，哇巴因诱发豚鼠心律失常的作用，提示其具有良好的抗心律失常作用；毛果芸香碱通过激动大鼠和豚鼠心肌M3受体而产生抗心律失常的作用。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.