复方风湿宁注射液镇痛作用的实验研究

目的:研究复方风湿宁注射液镇痛作用。方法:采用热板致痛法,醋酸致痛法和甲醛致痛法观察复方风湿宁注射液的镇痛作用;采用大鼠角叉菜胶性关节炎模型并测定角叉菜胶性关节炎模型大鼠致炎足炎症渗出液中前列腺素E2(PGE2)含量。结果:复方风湿宁注射液显著提高热致痛时小鼠的痛阈值及痛阈提高率,与空白对照组比较(P<0.05);显著减少醋酸致痛时小鼠扭体反应的次数及缩短小鼠扭体反应出现的时间,与空白对照组比较(P<0.01～0.05);显著减少甲醛致痛小鼠在15～30min时相内的舔足时间,与空白对照组比较(P<0.05);显著减少角叉菜胶性关节炎模型大鼠致炎足炎症渗出液中PGE2含量。结论:复方风湿宁注射液具有一定镇痛作用,其机制可能与抑制PGE2合成与释放有关。     

骨湿宁治疗风湿性关节炎的实验研究

目的:观察骨湿宁的主要药理作用。方法:采用佐剂、角叉菜胶、尿酸钠等引发大鼠关节炎症或疼痛模型、小鼠热板、醋酸扭体法以及腹腔毛细血管通透性来评价骨湿宁的抗炎、镇痛作用。结果:骨湿宁能抑制大鼠佐剂性关节炎的原发性和继发性病变;抑制角叉菜胶所致的大鼠炎症肿胀;对由大鼠尿酸钠关节炎致痛、小鼠热板、醋酸扭体致痛均有明显的镇痛作用;并具有降低小鼠腹腔毛细血管通透性、抑制大鼠棉球致组织增生的作用。结论:骨湿宁具有一定的抗炎、镇痛作用     

骨湿宁治疗风湿性关节炎的实验研究

目的：观察骨湿宁的主要药理作用。方法：采用佐剂，角叉菜胶，尿酸钠等引发大鼠关节炎症或疼痛模型，小鼠热板，醋酸扭体法以及腹腔毛细血管通透性来评价骨湿宁的抗炎，镇痛作用。结果：骨湿宁能抑制大鼠佐剂性关系炎的原发性和继发性病变；抑制角叉菜胶所致的大鼠炎症肿胀；对由大鼠尿酸钠关节炎致痛，小鼠热板，醋酸扭体致痛均有明显的镇痛作用；并具有降低小鼠腹腔毛细血管通透性，抑制大鼠棉球致组织增生的作用。结论：骨湿宁具有一定的抗炎，镇痛作用。     

苯胺洛芬注射液镇痛作用及镇痛部位研究

目的研究苯胺洛芬注射液对大鼠单足致炎急性炎症模型和大鼠单发性关节慢性病理性炎症模型的镇痛作用,并对其镇痛部位进行分析。方法通过角叉菜胶致大鼠单足致炎后的后肢压痛实验和完全弗氏佐剂致大鼠单发性关节炎性疼痛实验,测定致炎足和非致炎足痛阈值和屈伸关节评分。结果在大鼠急性炎症模型和慢性病理性炎症模型中,苯胺洛芬注射液25.2、75.6 mg·kg-1可提升致炎足的痛阈值,但对非致炎足的痛阈值无明显影响,致炎足和非致炎足痛阈值变化情况与氟比洛芬酯注射液相当,而喷他佐辛注射液对致炎足和非致炎足均有镇痛作用。结论苯胺洛芬注射液发挥镇痛作用的部位主要在外周,这与非甾体类抗炎镇痛药的作用部位相似。     

复方甘草酸苷对佐剂性关节炎大鼠血清中TNF-α、IL-1和IL-6表达水平的影响

目的:研究复方甘草酸苷对佐剂性关节炎大鼠血清中TNF-αIL-1和IL-6表达水平的影响,以探讨复方甘草酸苷对佐剂性关节炎的治疗作用.方法:通过给大鼠右后足跖部皮下注射完全弗氏佐剂(CFA)建立类风湿性关节炎的动物模型(AA),在致炎后第14d,大鼠继发性关节炎出现.开始在治疗组AA大鼠腹腔注射复方甘草酸苷注射液2mg...     

大麻二酚抗类风湿关节炎作用研究

目的 观察工业大麻中提取分离得到的大麻二酚的抗类风湿关节炎作用.方法 建立角叉菜胶致大鼠急性炎症模型和佐剂诱导的大鼠关节炎模型,测定大麻二酚5、7.5、10和20 mg/kg各剂量组大鼠灌胃后不同时间的肿胀值变化,并与艾瑞昔布阳性对照组比较.结果 与角叉菜胶致大鼠急性炎症模型组相比,大麻二酚各剂量给药组大鼠肿胀值均下降,并随给药剂量和时间的增加抗炎作用逐渐增强,其中20 mg/kg大麻二酚给药后3h肿胀值和肿胀率均较阳性对照组降低,但差异均无统计学意义;与佐剂诱导的大鼠关节炎模型组相比,大麻二酚各给药组显示出一定的量效关系,且10 mg/kg大麻二酚剂量组给药后第12d以及20 mg/kg剂量组给药后第10和12d的肿胀值和肿胀率均显著降低(P＜0.05,P＜ 0.01),而大麻二酚各剂量组与阳性对照组相比差异并无统计学意义.结论 大麻二酚对角叉菜胶致大鼠急性炎症和佐剂诱导的大鼠关节炎模型均有一定作用.     

广藿香叶挥发油抗炎作用机制实验研究

目的对广藿香叶挥发油抗炎机制进行实验研究。方法通过研究广藿香叶挥发油对角叉菜胶致大鼠足肿炎症模型组织和血清中前列腺素E2(PGE2)、丙二醛(MDA)、一氧化氮(NO)含量的影响,探讨广藿香叶抗炎作用机理。结果广藿香叶挥发油能明显降低大鼠角叉菜胶性炎症模型组织和血清中的PGE2和MDA的含量,能降低角叉菜胶致大鼠足肿炎症模型血清中NO的含量。结论广藿香叶挥发油抗炎作用机制与抑制炎症组织PGE2合成、减少炎症组织中MDA堆积,降低NO含量有关。     

基于网络药理学和分子对接探讨复方风湿宁片治疗类风湿关节炎的作用机制

目的 采用网络药理学联合分子对接技术探讨复方风湿宁片治疗类风湿性关节炎的作用机制。方法 通过TCMSP、BATMAN-TCM、Swiss TargetPrediction数据库及文献报道收集复方风湿宁片的活性化学成分靶点,并使用GeneCards数据库检索类风湿关节炎的疾病靶点,将两者取交集,并通过绘制“复方风湿宁片–活性成分–靶点–通路–类风湿关节炎”网络图。对复方风湿宁片中的活性成分与类风湿关节炎靶点进行分子对接。结果 通过网络药理学分析得到复方风湿宁片中有34种活性化学成分,对应1059个靶点,与类风湿关节炎靶点交集356个。通过KEGG富集分析发现复方风湿宁片主要可能在肿瘤坏死因子（TNF）信号通路、白细胞介素-17(IL-17)信号通路、Th17细胞分化、T细胞受体信号通路、Toll样受体（TLR）信号通路、核因子κB(NF-κB)信号通路、Th1和Th2细胞分化、Janus激酶（JAK）-信号传导和转录激活蛋白3(STAT3)信号通路、B细胞受体信号通路和类风湿性关节炎等通路上发挥治疗作用。蛋白激酶B(Akt1)、前列腺素内过氧化物酶2(PTGS2)、丝裂原活化蛋白激酶1(...     

701跌打镇痛膏抗炎作用的实验研究

目的考察701跌打镇痛膏的抗炎作用,为其临床应用提供实验依据。方法通过角叉菜胶致大鼠足跖肿胀模型、二甲苯致小鼠耳肿胀模型、完全氟氏佐剂致大鼠关节炎模型,考察701跌打镇痛膏的抗炎作用。结果 701跌打镇痛膏单次腹部敷贴给药后能明显降低角叉菜胶致SD大鼠足肿胀的足容积和足肿胀度,药效达峰时间约为给药后4 h;连续腹部敷贴给药5 d后能明显降低二甲苯引起的小鼠耳廓肿胀度,抗炎作用具有明显的量效关系;对大鼠佐剂性关节炎模型未见明显作用。结论 701跌打镇痛膏对急性渗出性炎症具有明显的改善作用,但对免疫性炎症作用不明显。     

骨痹宁胶囊的药效学研究

目的 研究骨痹宁胶囊的抗炎、消肿、镇痛作用,为临床用药提供理论依据. 方法 通过研究骨痹宁胶囊对二甲苯致小鼠耳肿胀的影响和对1%角叉菜胶致大鼠足跖肿胀的影响来考察其抗炎、消肿作用;研究对小鼠热板法痛阈值的影响及对0.6%醋酸所致小鼠扭转次数的影响考察镇痛作用. 结果 骨痹宁胶囊对二甲苯致小鼠耳肿胀有明显抑制作用;可抑制角叉菜胶致大鼠足跖肿胀;提高小鼠热板法痛阈值;减少0.6%醋酸所致小鼠扭转反应次数. 结论 骨痹宁胶囊具有抗炎、消肿、镇痛作用,提示骨痹宁胶囊对类风湿关节炎有较好的疗效.     

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.     

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.     

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.