安神定志丸对癫痫小鼠的影响

目的:探讨安神定志丸对小鼠癫痫模型的影响。方法:通过给小鼠硝酸士的宁注射液、戊四氮及对小鼠进行电刺激制备癫痫发作模型,以生理盐水作对照,研究药物对动物癫痫发作的抑制作用。结果:安神定志丸对戊四氮所致的小鼠惊厥,能降低试验动物死亡率(P<0.05);对士的宁所致的试验动物惊厥,能延长惊厥发生的潜伏期(P<0.05)和死亡时间(P<0.05);能降低电惊厥动物的惊厥发生率(P<0.05)。结论:安神定志丸具有明显的抗癫痫作用。     

天麻定痫康胶囊抗癫痫作用的实验研究

目的 观察天麻定痫康抗癫痫作用.方法 天麻定痫康胶囊(按剂量分3个组)予小鼠灌胃给药,于末次给药后1 h,采用士的宁注射液腹腔注射引起小鼠惊厥,观察小鼠惊厥发生率、潜伏期及惊厥导致死亡率.另设苯妥英钠组为阳性对照组,模型对照组给予生理盐水.结果 各剂量组天麻定痫康胶囊均可显著延长士的宁注射液致小鼠惊厥潜伏期,其中1 g/kg和2g/kg天麻定痫康尚可显著降低惊厥后死亡率.结论 天麻定痫康胶囊有抗癫痫作用.     

藏药七十味珍珠丸对惊厥小鼠脑内氨基酸含量的影响

目的　观察七十味珍珠丸的抗惊厥作用及作用机制。方法　七十味珍珠丸ig给药,使用硫代氨基脲制成惊厥小鼠模型,测定惊厥开始时间、致死率;采用高压液相色谱仪测定小鼠脑内抑制性氨基酸γ氨基丁酸(GABA)、甘氨酸(Gly)和兴奋性氨基酸谷氨酸(Glu)、天门冬氨酸(Asp)的含量。结果　七十味珍珠丸对硫代氨基脲所致惊厥的开始时间,具有显著延迟作用,可明显减少小鼠致死率。有升高惊厥小鼠脑内GABA ,降低脑内Glu含量的作用趋势,但无显著差异(P>0.05) ,而对Glu/GABA的比值,却有明显的降低作用(P<0.05、P<0.01) ,使Glu/GABA保持正常动物的水平,即维持中枢神经系统兴奋和抑制状态平衡的作用,阻止惊厥发生。结论　该药具有抗惊厥作用,其作用机制可能是通过调节脑内兴奋性和抑制性氨基酸的平衡来实现的     

藏药七十味珍珠丸对惊厥小鼠脑内氨基酸含量的影响

目的　观察七十味珍珠丸的抗惊厥作用及作用机制。方法　七十味珍珠丸ig给药 ,使用硫代氨基脲制成惊厥小鼠模型 ,测定惊厥开始时间、致死率 ;采用高压液相色谱仪测定小鼠脑内抑制性氨基酸γ 氨基丁酸 (GABA)、甘氨酸 (Gly)和兴奋性氨基酸谷氨酸 (Glu)、天门冬氨酸 (Asp)的含量。 结果　七十味珍珠丸对硫代氨基脲所致惊厥的开始时间 ,具有显著延迟作用 ,可明显减少小鼠致死率。有升高惊厥小鼠脑内GABA ,降低脑内Glu含量的作用趋势 ,但无显著差异 (P >0 .0 5 ) ,而对Glu/GABA的比值 ,却有明显的降低作用 (P <0 .0 5、P <0 .0 1) ,使Glu/GABA保持正常动物的水平 ,即维持中枢神经系统兴奋和抑制状态平衡的作用 ,阻止惊厥发生。结论　该药具有抗惊厥作用 ,其作用机制可能是通过调节脑内兴奋性和抑制性氨基酸的平衡来实现的     

丹皮总甙抗实验性癫痫的研究

目的：了解丹皮总甙是否具有抗小鼠实验性癫痫作用。方法：采用最大电惊厥（ＭＥＳ）及戊四唑、士的宁、氨基脲等化学性惊厥模型，观察丹皮总甙（ｔｏｔａｌｇｌｕｃｏｓｉｄｅｓｏｆｍｏｕｔａｎｃｏｒｔｅｒ，ＴＧＭ）对动物惊厥发作数、发作潜伏期及动物存活时间等指标的影响，从而分析ＴＧＭ抗惊厥作用及其时量效关系。结果：ＴＧＭ（６０、８０ｍｇ·ｋｇ－１ｉｐ；８０ｍｇ·ｋｇ－１ｉｇ）可减少小鼠ＭＥＳ发作数，其峰时为药后０．５～１ｈ；ＴＧＭ（６０～８０ｍｇ·ｋｇ－１ｉｇ）可延长戊四唑、士的宁、氨基脲所致小鼠惊厥的潜伏期及动物存活时间；同时ＴＧＭ（４０ｍｇ·ｋｇ－１ｉｐ）可增强苯巴比妥抗上述惊厥之作用。结论：ＴＧＭ（６０～８０ｍｇ·ｋｇ－１）呈剂量依赖性对抗小鼠ＭＥＳ及戊四唑、士的宁、氨基脲所致小鼠化学性惊厥，并可增强苯巴比妥抗惊厥作用。     

苯巴比妥钠对药物士的宁所致惊厥的保护作用

目的:探索苯巴比妥钠对药物士的宁所致惊厥的保护作用,并为苯巴比妥钠保护士的宁所致惊厥提供理论和实验基础。方法:选取健康小鼠60只,随机选取50只分5组,按浓度梯度腹腔内注射10%的苯巴比妥钠溶液,另外10只腹腔内注射生理盐水(NS)0.1ml/10g,30min后注射硝酸士的宁(ml)1.5mg/kg,进行Racine行为分级,凡小鼠无显示Ⅳ~V级的发作认为抗惊厥。结果:注射苯巴比妥钠组的小鼠与注射生理盐水组的小鼠相比较,前者在注射浓度为1.5mg/kg硝酸士的宁后30min内惊厥潜伏期、持续期延长,惊厥发生率、死亡率明显降低。结论:对于硝酸士的宁所致的惊厥,苯巴比妥钠可降低小鼠惊厥的发生率和死亡率。     

石菖蒲挥发油和水溶性成分对癫痫小鼠脑组织SOD、LPO、NO的影响

目的:研究石菖蒲挥发油和水溶性成分对士的宁致癫痫小鼠脑组织SOD、LPO、NO的影响.方法:石菖蒲挥发油和水溶性成分灌胃小鼠用士的宁造成癫痫模型测定3 d后,小鼠脑组织SOD、LPO、NO的含量.结果:挥发油组,水提液组能增加小鼠脑组织SOD含量;挥发油组,水提液组、去油水煎液组能显著降低脑内LPO水平,除去油水煎液低剂量组外,其余各组均有降低脑内NO的作用.结论:实验结果提示活跃的自由基反应可能参与了癫痫的发病,石菖蒲挥发油和水溶性成分能有效清除自由基、阻止过氧化物形成,减少NO的神经毒性,对脑细胞具有良好的保护作用.     

灵芝颗粒剂对小鼠镇静催眠和免疫功能的影响

目的：观察灵芝颗粒剂的镇静催眠、增强免疫功能作用。方法：采用开阔法、戊巴比妥钠致小鼠睡眠时间、士的宁致小鼠惊厥法，测定小鼠脾指数、胸腺指数和白细胞数。结果：灵芝颗粒剂能明显减少小鼠自主活动，缩短戊巴比妥钠致小鼠睡眠潜伏期，延长戊巴比妥钠致小鼠睡眠时间，能对抗士的宁致小鼠惊厥的作用，能升高小鼠脾指数、胸腺指数和白细胞数。结论：灵芝颗粒剂具有镇静催眠、增强免疫功能的作用。     

川芎嗪抗小鼠实验性癫痫的研究

目的:系统评价川芎嗪(Tetramethylpyrazine,TMP)是否具有抗小鼠实验性癫痫作用。方法:采用最大电惊厥(MES)及戊四氮、士的宁、匹罗卡品等癫痫模型。观察川芎嗪(TMP)低、中、高(200、400、800mg.kg-1)剂量对动物惊厥发作数、阵挛潜伏期及动物存活时间等指标的影响,从而分析川芎嗪抗惊厥作用及其时量关系。结果:中、高剂量(400、800mg.kg-1)川芎嗪可明显减少MES发作次数,延长戊四氮、士的宁所致小鼠阵挛潜伏期,同时延长死亡时间。高剂量川芎嗪可延长小鼠匹罗卡品癫痫模型的阵挛时间,与模型组相比,差异有统计学意义。结论:川芎嗪对癫痫有一定防治作用,并存在一定的量效关系。     

安痫宁冲剂抗惊厥作用的实验研究

目的：研究安痫宁冲剂的抗惊厥作用。方法：选用电惊厥及药物性惊厥法观察惊厥潜伏期、惊厥百分数、死亡率。结果：安痫宁高剂量可明显延长小鼠惊厥潜伏期，中、低剂量有延长小鼠惊厥潜伏期的趋势，安痫宁高剂量组惊厥百分率为75％，与空白组相比有差异。结论：安痫宁具有抗惊厥作用。     

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.

---

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.