海星甾醇抗实验性心律失常作用

目的研究海星甾醇［丁二酸(5-雄甾烯-17-酮-3β-羟基)二酯］对实验性心律失常的作用。方法通过iv乌头碱、哇巴因、BaCl₂、肾上腺素、冠脉结扎和电刺激复制各种动物心律失常模型，在预先po海星甾醇，观察其对实验性心律失常的预防作用。结果海星甾醇可分别增加乌头碱、哇巴因、BaCl₂诱发心律失常所需剂量，延迟VP,VT,VF和CA的出现；可延迟肾上腺素所致兔VT的出现，缩短恢复正常心律的时间；可减少冠脉结扎再灌注所致室性心律失常；可提高电刺激兔所致室颤阈值。结论海星甾醇具有一定的抗实验性心律失常作用。     

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。     

苄普地尔抗心律失常作用

苄普地尔iv能明显提高乌头碱诱发大鼠心律失常用量及豚鼠心脏哇巴因中毒耐量;对BaCI_2、Adr诱发的实验性心律失常有明显对抗作用;对大鼠冠脉结扎复灌注引起的心律失常有保护作用。     

小叶锦鸡儿提取物对大鼠实验性心律失常的影响

目的研究小叶锦鸡儿正丁醇提取物对药物诱发大鼠实验性心律失常的影响。方法制备乌头碱、氯化钡(BaCl2)诱发大鼠实验性心律失常模型,将大鼠分为生理盐水对照组、阳性对照组和100、50 mg.kg-1小叶锦鸡儿正丁醇提取物组,分别于舌下静脉给药1次,记录给予乌头碱后出现室性早搏(VP)、室性心动过速(VT)、心室颤动(VF)时乌头碱的用量;记录给予BaCl2后心律失常出现的时间和维持的时间。结果小叶锦鸡儿正丁醇提取物的两个剂量可明显提高乌头碱所致大鼠发生的VP、VT、VF的用量;延长BaCl2诱发大鼠心律失常的出现时间,缩短维持时间。结论小叶锦鸡儿正丁醇提取物具有一定抗大鼠实验性心律失常的作用。     

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。     

胃复安对实验性心律失常的作用

MCP有对抗氯化钡诱发大白鼠心律失常的作用;对抗氯仿-肾上腺素诱发家兔的心律失常,能提高乌头碱诱发大鼠心律失常的用量、致室颤量和致死量、但对哇巴因诱发的心律失常无影响,不能改善结扎大白鼠冠状动脉造成的缺血性心律失常。有局部麻醉作用。     

去甲羟基安定抗心律失常药理作用研究

本文用大鼠乌头碱，冠脉结扎和家兔电刺激诱发心律失常模型研究了去甲羟基安定抗心律失常作用，结果证明：去甲羟基安定具有明显抗心律失常作用，特别对乌头硷和家兔性心律失常作用明显强大于大鼠冠脉结扎性心律失常，其作用机理可能和抑制钠通道有关，本研究提示该药在临床上可用于室性早搏等心律失常。     

刺乌头碱对麻醉大鼠心电图的影响及其抗实验性心律失常作用

目的与方法：给麻醉大鼠恒速ｉｖ刺乌头碱观察ＥＣＧ变化及ｉｐ小剂量刺乌头碱对动物实验性心律失常的影响。结果：ｉｖ剂量至２．５４±０．０６ｍｇ·ｋｇ－１时，ＨＲ显著减慢，Ｐ－Ｒ间期显著延长，当剂量增至４．１２～８．１９ｍｇ·ｋｇ－１时，可分别引起ＶＰ、ＶＴ、ＶＦ及ＣＡ等；经ｉｐ０．５ｍｇ·ｋｇ－１时，则能对抗乌头碱、氯化钡诱发的大鼠心律失常，显著提高哇巴因诱发豚鼠心律失常的剂量。结论：小剂量刺乌头碱具有抗心律失常作用，而大剂量又可诱发心律失常。     

氧化苦参碱抗大鼠实验性心律失常的作用探讨

目的观察氧化苦参碱的抗心律失常作用。方法将SD大鼠随机分为两组,制作乌头碱诱发大鼠室性心律失常模型和结扎左冠状动脉前降支诱发的大鼠室性心律失常,以及对氯仿所致大鼠的室颤,一组静脉注射生理盐水,另一组静注氧化苦参碱,观察两组心律失常的变化。结果氧化苦参(OM)20 mg/kg能明显对抗乌头碱和结扎左冠状动脉前降支诱发的大鼠室性心律失常,也能预防对氯仿所致小鼠的室颤的发生。结论氧化苦参碱对大鼠有明显的抗心律失常作用,此实验为氧化苦参碱的临床应用提供了实验依据。     

碘杂环化合物的抗心律失常作用

碘杂环-64能防治乌头碱、氯化钡和结扎冠状动脉诱发的大鼠心律失常,推迟肾上腺素—氯仿诱发家兔心律失常的发作和缩短心律失常持续期,提高哇巴因诱发豚鼠心律失常的剂量,显著降低乙酰胆碱(Ach)—氯化钙诱发小鼠房颤(扑)的发生率。碘杂环-64减慢心率与迷走神经兴奋和β受体阻滞无关。     

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.     

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.