Cedemex对吗啡依赖性大鼠不同脑区3种单胺类神经递质的影响

目的:观察Cedemex对吗啡依赖性大鼠不同脑区单胺类神经递质的影响.方法:采用反相高效液相色谱-荧光检测法分别测定大鼠腹侧被盖区(VTA)、海马区、大脑皮层和伏隔核(NAe)共4个脑区的多巴胺(DA),去甲肾上腺素(NE)、及5-羟色胺(5-HT)的含量.结果:吗啡依赖大鼠脑内各区的DA,NE及5-HT等单胺类神经递质发生紊乱,其含量均明显高于正常.Cedemex能够促进吗啡依赖戒断后脑区内DA,NE及5-HT等单胺类神经递质含量趋于正常.结论:单胺类递质(DA,NE,5-HT)在吗啡依赖中可能起重要作用,Cedemex改善吗啡依赖性大鼠脑内单胺类神经递质的含量,可能是Cedemex临床治疗的作用机制之一.     

半夏泻心汤对高龄合并D-半乳糖诱导衰老模型大鼠的影响

目的:研究半夏泻心汤对衰老模型大鼠学习记忆能力和脑内神经递质的影响。方法:高龄大鼠ip D-半乳糖125 mg.kg~(-1),每天1次,连续4周造成衰老模型动物,用水迷宫检测衰老大鼠学习记忆能力,用Elisa法检测脑组内多巴胺(DA)、去甲肾上腺素(NE)和五羟色胺(5-HT)等的含量,用Elisa法检测血清降钙素相关基因肽(CGRP)、内皮素-1(ET-1)的水平,用免疫组织化学方法检测脑组织内脑源性神经营养因子(BDNF)的表达。结果:半夏泻心汤给药组可明显缩短逃避潜伏期;半夏泻心汤10和5 g.kg~(-1)给药组海马区脑组织内DA和5-HT含量明显升高,可明显上调脑组织额叶皮层区BDNF的表达,但半夏泻心汤对血清CGRP和ET-1未见明显影响。结论:半夏泻心汤对衰老模型大鼠脑内单胺类神经递质水平与额叶皮层BDNF的表达有显著影响。     

AQP4参与雌激素对单胺类神经递质的调节作用

目的：探讨AQP4对雌激素调节神经递质作用的影响。方法：应用雄性AQP4基因敲除型CD1小鼠与野生型CD1小鼠，给予不同剂量雌激素后测定不同脑区中单胺类神经递质的含量。结果：AQP4基因敲除型雄性小鼠纹状体多巴胺（DA）及5-羟色胺（5-HT）、皮层去甲肾上腺素（NE）含量增加；海马NE、下丘脑DA水平下降。同时，给予雌激素后，野生型雄性CD1小鼠纹状体DA、5-HT含量及海马5-HT含量升高，皮层DA、5-HT水平及下丘脑NE、DA水平下降；而雌激素对AQP4敲除型雄性CD1小鼠单胺类递质无显著影响。结论：AQP4敲除可改变雌激素对单胺类递质水平的调节作用，对纹状体内DA水平的影响尤为显著。AQP4参与了雌激素对单胺类神经递质的调节。     

白松片对慢性应激大鼠海马单胺类神经递质含量的影响

目的:观察中药白松片对应激大鼠海马单胺类神经递质含量的影响。方法:健康成年雄性SD大鼠42只,随机分为正常对照组、模型对照组、氟西汀对照组(1.8mg·kg-1)及白松片3个剂量(4.32,13.0,21.6g·kg-1,生药量)组。每只大鼠每日灌胃给药1次,连续14d。给药d6始,通过强迫游泳建立应激大鼠模型。用高效液相色谱-电化学法测定大鼠海马单胺类神经递质及其代谢产物的含量。结果:模型对照组大鼠海马去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)含量及多巴胺/3,4-二羟苯乙酸(DA/DOPAC)和5-羟色胺/5-羟吲哚乙酸(5-HT/5-HIAA)的比值分别为(4.7±s1.3)nmol·g-1,(47±12)nmol·g-1,(0.97±0.22)nmol·g-1,19±4,0.23±0.06,低于正常对照组(P<0.05或P<0.01);NE/5-HT比值(4.9±0.9)高于正常对照组(P<0.01);用白松片预防给药可使模型大鼠海马NE,DA和5-HT含量及NE/5HT,DA/DOPAC和5-HT/5-HIAA的比值恢复至正常水平(P<0.05或P<0.01)。结论:白松片可能通过提高NE,DA及5-HT的含量并降低其代谢率来发挥其抗抑郁作用。     

如意珍宝片对血管性痴呆模型大鼠的保护作用

目的 研究如意珍宝片对血管性痴呆(VD)大鼠的保护作用。方法 采用改良双侧颈总动脉永久性结扎法制备大鼠VD模型,以Y迷宫为学习记忆评价指标,并测定VD大鼠脑内多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)3种单胺类神经递质水平。结果 如意珍宝片能显著的增加Y迷宫的正确次数和提高脑内3种单胺类神经递质水平。结论 如意珍宝片能提高VD大鼠学习记忆能力,升高脑内单胺类神经递质水平,从而改善大脑皮层的兴奋性,激活脑损伤后的学习记忆过程。     

龙眼参多糖对SAMP8学习记忆及脑组织单胺类神经递质含量影响的研究

目的:研究龙眼参(LYS)多糖对快速老化小白鼠(SAMP8)学习记忆及脑组织单胺类神经递质含量的影响。方法:选用6月龄的SAMP850只,随机分为SAMP8、石杉碱甲和LYS多糖低、中、高剂量组,每组10只,另选用6月龄正常老化小白鼠(SAMR1)10只作为正常对照组。各组分别ig相应药物40d后,采用Morris水迷宫法检测小鼠的学习记忆能力,采用高效液相色谱法测定小鼠脑组织去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)的含量。结果:与正常对照组比较,SAMP8组的学习记忆能力显著下降,且其脑组织NE、DA、5-HT的含量显著降低(P<0·05或P<0·01);与SAMP8组比较,LYS多糖组小鼠的学习记忆能力及脑组织单胺类神经递质的含量均显著提高(P<0·05或P<0·01)。结论:LYS多糖可有效调整中枢神经递质的合成及提高学习记忆能力,具有良好的抗痴呆作用。     

经前平颗粒对愤怒情绪模型大鼠不同脑区单胺类神经递质的影响及分析

目的通过研究愤怒模型大鼠不同脑区单胺类神经递质的含量变化,探讨愤怒发生的微观机制及中药经前平颗粒的可能干预机制。方法采用社会隔离结合居住入侵方法制备愤怒大鼠模型,分别为正常组、愤怒模型组、经前平颗粒给药组;运用高效液相色谱法检测各组大鼠不同脑区单胺类神经递质的含量。结果与正常对照组相比,愤模组大鼠下丘脑NE含量明显下降(P<0.01),给药后愤药组大鼠额叶皮质NE含量异常变化得以纠正(P<0.05);愤模组额叶皮质、顶区皮质、海马DA含量下降(P<0.01,P<0.01,P<0.01),而下丘脑DA含量则上升(P<0.01),给药后下丘脑DA含量恢复至正常水平(P<0.01)。愤模组大鼠下丘脑5-HT含量降低(P<0.01)。结论大鼠愤怒情绪反应与下丘脑NE含量下降,额叶皮质、顶区皮质、海马DA、下丘脑5-HT含量下降,下丘脑DA含量上升有关;干预药物经前平颗粒可能通过纠正上述指标异常变化而发挥药理作用。综上所述,本研究为进一步研究愤怒情绪发病机制及调肝方药治病机制提供理论基础和方向。     

乌灵菌粉对脑卒中后抑郁大鼠海马区单胺类神经递质及

目的:观察乌灵菌粉对脑卒中后抑郁(PSD)大鼠的行为学改变及脑内单胺类神经递质的影响。方法:采用双侧颈总动脉永久性结扎后并给予行为限制的方法制作PSD大鼠模型,采用敞箱试验(open-field)观察大鼠行为学变化,并用高效液相法检测大鼠海马组织中4种单胺类神经递质去甲肾上腺素(L-NE)、多巴胺(DA)、5-羟色胺(5-HT)和5-羟基吲哚乙酸(5-HIAA)的含量,对比观察了乌灵菌粉组(0.3 g.kg-1,qd,ig,28 d)、盐酸氟西汀组(0.75 mg.kg-1,qd,ig,28 d)、模型组及假手术组的变化。结果:与假手术组比较,模型组行为学能力下降,脑内NE,DA,5-HT和5-HIAA下降(P<0.05);与模型组比较,乌灵菌粉组及盐酸氟西汀组行为学能力改善,脑内5-HT和5-HIAA水平上升(P<0.05),而两组间比较统计学差异不明显(P>0.05)。结论:乌灵菌粉可改善脑卒中后抑郁大鼠的行为学改变,其作用可能通过调节脑内5-HT水平。     

山奈酚对乳腺癌抑郁模型大鼠的抗抑郁作用研究

目的 探讨山奈酚对实验性乳腺癌抑郁大鼠的抗抑郁作用。方法 90只大鼠随机分为对照组、乳腺癌组、抑郁组、复合模型组、氟西汀组、山奈酚组,每组15只。通过慢性不可预知性轻度应激方法建立大鼠抑郁模型,以二甲基苯蒽为诱导剂建立乳腺癌大鼠模型。采用旷场实验垂直运动次数及水平活动总路程观察各组大鼠自主活动;液质联检分析各组大鼠脑内海马及前额叶皮质单胺类神经递质,包括去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)和5-羟色胺(5-hydroxytryptamine,5-HT)含量的变化。结果 乳腺癌组自主活动均减少,但与对照组比较无显著性差异;抑郁组和复合模型组自主活动减少,与对照组比较差异均有显著性(P<0.01);与复合模型组相比,山奈酚组与氟西汀组垂直运动次数及水平活动总路程均显著增加(P<0.05或P<0.01)。与复合模型组比较,氟西汀组海马区DA、5-HT含量显著增高(P<0.01),前额叶皮质DA、NE、5-HT浓度均显著性增高(P<0.05);山奈酚组与复合模型组比较,海马部位NE含量明显增高(P<0.05),前额叶皮质部位DA、NE、5-HT浓度均显著性增高(P <0.05或P <0.01)。结论 山奈酚具有显著抗大鼠抑郁作用,可能通过提高前额叶皮质部位NE、DA、5-HT递质水平达到抗抑郁作用。     

七十味珍珠丸对脑损伤大鼠脑内单胺类神经递质的影响

目的 :通过对脑损伤大鼠脑内单胺类神经递质含量的测定 ,研究七十味珍珠丸 (RNSP)治疗脑血管疾病的作用机理。方法 :RNSP ig给药后 ,制成脑损伤病理模型 ,采用荧光分光光度法检测脑内 5 -羟色胺 (5 -HT)、去甲肾上腺素 (NA)、多巴胺(DA)含量。结果 :RNSP具有显著降低脑损伤所致大鼠脑内 5 -HT、NA含量升高的作用 (P<0 .0 5、P<0 .0 1) ,对 DA含量的抑制 ,也有一定的作用趋势 (P>0 .0 5 )。结论 :RNSP治疗脑血管疾病的作用机理 ,可能与它具有调节脑内单胺类神经递质的作用有关     

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.

---

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.