知母宁体外抗甲型流感病毒作用研究

目的:考察知母宁体外抗甲型流感病毒作用.方法:以利巴韦林作阳性对照药物,用中性红染色法测定知母宁不同加药方式对甲型人流感病毒H1N1的体外抑制作用及其时效关系.结果:知母宁对甲型人流感病毒具明显的综合抑制作用及抑制病毒吸附后的复制增殖作用,这两种作用的半数有效浓度(EC50)分别为0.70及0.76 mg·ml-1.知母宁对病毒吸附的预防作用弱,无直接杀伤病毒的作用.随药物作用时间延长,知母宁在低浓度抗病毒有效率呈减小趋势,在高浓度时(≥1.4 mg·ml-1)其抗病毒能力基本不变.同时知母宁可明显降低病毒的感染性.结论:知母宁具有明显的体外抗甲型人流感病毒作用.     

利巴韦林注射液体内外抗流感病毒作用研究

利巴韦林具有广谱抗病毒活性, 对多种DNA或RNA病毒体内外都有抑制作用。本文对利巴韦林注射液的体内外抗流感病毒活性进行研究, 体外实验采用细胞病变 (CPE) 法研究了利巴韦林注射液对流感病毒甲乙型的活性, 体内实验采用小鼠模型研究了利巴韦林注射液对流感病毒A/FM/1/47 (H1N1) 鼠肺适应株感染小鼠的保护作用。结果显示, 在体外实验中, 利巴韦林注射液对所检测的7种病毒株均有显著的抑制活性; 在体内实验中, 利巴韦林注射液可以显著提高感染小鼠的存活率和平均生活日, 显著改善感染小鼠的肺病变和肺指数。     

滨蒿总黄酮体内外抗甲型流感病毒作用的研究

目的研究滨蒿总黄酮在体内外抗甲型流感病毒的作用。方法将昆明小鼠随机分为7组,即滨蒿总黄酮0.10,0.20和0.40g·kg-1组、利巴韦林组、复方一枝蒿颗粒组、病毒对照组和对照组,采用甲型流感病毒PR/8/H1N1滴鼻感染小鼠造成肺炎模型,连续灌胃给药7d。计算肺指数并测定肺匀浆中IL-6和IL-8的水平;体外Cytopathic effect(CPE)法观察滨蒿总黄酮抗甲型流感病毒A/京防/262/95(H1N1)的作用。结果滨蒿总黄酮0.10,0.20和0.40g·kg-1给药后能明显降低甲型流感病毒PR/8/H1N1感染小鼠的肺指数,明显降低肺匀浆中的IL-6水平(P<0.01);滨蒿总黄酮0.40g·kg-1剂量组可明显降低肺匀浆中IL-8的水平(P<0.05);滨蒿总黄酮在体外对A/京防/262/95(H1N1)的IC50值为6.9μg·mL-1,治疗指数(SI)为55.1。结论滨蒿总黄酮对甲型流感病毒感染小鼠有明显的治疗作用,对甲型流感病毒所致细胞病变有明显的抑制作用,表明其有良好的抗甲型流感病毒作用。     

绿豆肽调节病毒性肺炎幼鼠T细胞免疫、减轻炎症反应

目的:探讨绿豆肽调节病毒性肺炎幼鼠T细胞免疫、减轻炎症反应机理.方法:对3周龄昆明(KM)幼鼠采用A型流感病毒(H1N1)滴鼻法建立病毒性肺炎模型,将建模成功幼鼠随机分为模型组、利巴韦林组(46 mg·kg-1·d-1)、绿豆肽低、中、高剂量组(50,100,200 mg·kg mb-1·d-1),每组10只;另取10...     

黄芩苷与利巴韦林联用体内外抗流感病毒作用

目的评价黄芩苷与利巴韦林联用体内外抗流感病毒作用,为其临床上联用提供实验依据。方法 CPE法和MTT法测定药物单用及联用对感染3种不同亚型流感病毒MD-CK细胞的保护效果,分别应用合并指数法(combination in-dex,CI)和MacSynergyⅡ分析法,分析黄芩苷与利巴韦林体外联用的相互作用。神经氨酸酶(NA)抑制试验测定黄芩苷对流感病毒NA活性的抑制作用。应用H1N1亚型流感病毒(FM1株)人工感染BALB/c小鼠模型,评价黄芩苷与利巴韦林联用对感染小鼠的保护作用。结果体外黄芩苷与利巴韦林联用对H1N1和H5N1病毒的抑制表现为相加作用,对H9N2病毒的抑制表现为协同作用。黄芩苷对3种亚型流感病毒NA的半数抑制浓度(IC50)在0.29～0.49 mmol.L-1范围。利巴韦林与黄芩苷联合给药与单独给药相比,提高感染小鼠的存活率,延长其存活时间。结论黄芩苷对流感病毒NA活性具有抑制作用。黄芩苷与利巴韦林在体外联用,对不同亚型流感病毒的抑制表现为相加或协同作用;二者联用对感染流感小鼠的保护效果明显优于单用。     

黄芩苷对FM1肺炎小鼠肺损伤的作用机制研究

目的研究黄芩苷对甲型流感病毒性肺炎小鼠肺组织炎性损伤的作用机制。方法将96只ICR鼠随机分为正常对照组、模型组、利巴韦林组(100 mg.kg-1),黄芩苷组(1 500、750、375 mg.kg-1)[5],每组16只。用流感病毒亚甲型鼠肺适应株A/FM/1/47(H1N1)感染小鼠,制备小鼠流感病毒性肺炎模型,用不同剂量黄芩苷溶液灌胃治疗后,观察肺组织H-E染色切片病理变化,采用RT-PCR测定肺组织c-jun、c-fos mRNA表达,采用Western blot测定肺组织c-jun、磷酸化c-jun蛋白表达,应用ELISA检测肺匀浆炎性细胞因子TNF-α、IL-1β的含量。结果黄芩苷750、375 mg.kg-1剂量均能明显减轻肺组织炎性损伤;明显降低c-jun、c-fosmRNA的表达(P<0.05,P<0.01),明显降低c-jun、磷酸化c-jun蛋白表达(P<0.01);明显抑制TNF-α、IL-1β的分泌(P<0.01)。结论黄芩苷能够缓解甲型流感病毒诱导的炎性病理损伤,其可能通过抑制流感病毒感染引起的转录因子AP-1高表达而降低炎性细胞因子的分泌水平,从而发挥抗流感病毒感染的作用。     

鼠尾草酸对甲型流感病毒的体外抑制作用研究

鼠尾草酸(carnosic acid, CA)是迷迭香与鼠尾草等植物中主要的酚二萜类活性成分,具有抗氧化、抗炎等作用,但目前未见CA抗流感病毒的相关报道。本研究通过病毒滴度测定方法评价了迷迭香中主要活性成分迷迭香酸、CA和熊果酸的抗流感病毒活性,发现CA在A549细胞中显著抑制流感病毒H5N1增殖,进一步通过间接免疫荧光、Western blot和实时荧光定量PCR等方法对CA的体外抗流感病毒作用进行了系统评价并初步探讨其作用机制。结果表明, CA在A549和MDCK细胞中可显著抑制流感病毒H5N1复制,半数有效浓度(EC₅₀)分别为4.30和3.64μmol·L^-1。同时, CA也抑制流感病毒2009panH1N1(EC₅₀:10.1μmol·L^-1)和H3N2(EC₅₀:12.8μmol·L^-1)在A549细胞中的复制。机制研究发现, CA对H5N1复制的抑制作用与其诱导A549细胞血红素加氧酶-1(HO-1)的表达并减少H5N1感染细胞中活性氧的水平...     

知母宁体外抗单纯疱疹病毒Ⅰ型体外活性研究

目的:对知母宁体外抗单纯疱疹病毒Ⅰ型的活性进行研究.方法:采用MTT比色法测定知母宁对Vero细胞的毒性作用.采用中性红染色法,以阿昔洛韦为阳性对照药物,考察不同给药方式与不同药物处理时间下知母宁体外抗单纯疱疹病毒Ⅰ型(HSV-ⅠSm44)的活性.结果:MTT法测得Vero细胞对知母宁的最大耐受浓度与半数中毒浓度(TC50)分别为0.29与3.66mg*ml-1.不同加药方式下,知母宁与阿昔洛韦均对HSV-ⅠSm44表现出综合抑制作用并能抑制病毒吸附后的复制增殖过程,这些作用总体上随药物浓度升高而增强,其中知母宁抗病毒有效率(ER%)最高达76.42%.知母宁预防HSV-Ⅰ病毒吸附的作用较弱,但其在高浓度(2.08mg*ml-1以上)对HSV-Ⅰ具强的直接杀伤作用,最高ER%值为98.86%.随药物处理时间延长,低浓度知母宁抗HSV-Ⅰ的ER%值递减,2.08mg*ml-1以上知母宁的ER%值变化小.在不同药物处理时间下,知母宁及阿昔洛韦组病毒的感染性均较平行设置的病毒对照组减弱,且知母宁组的感染力较阳性药物组更弱.知母宁组病毒感染力下降值△lgTCID50随处理时间增加而增加.结论:知母宁在体外从多个作用点较强地抑制单纯疱疹病毒Ⅰ型活性.     

一清胶囊抗甲型H1N1流感病毒作用

目的 研究一清胶囊抗甲型H1N1流感病毒作用。方法 采用小鼠气管内注入甲型流感病毒鼠肺适应株A/PR/8/34(H1N1)病毒液建立病毒感染小鼠模型,以肺指数、肺指数抑制率、小鼠累积死亡率为指标,评价一清胶囊体内抗甲型H1N1流感病毒作用。结果 7.3 g·kg^-1一清胶囊(原生药)可降低病毒感染小鼠的肺脏指数(P<0.05)和小鼠感染病毒后7~9 d内的死亡率(P<0.01)。结论 一清胶囊具有明显的抗甲型H1N1流感病毒作用。     

Study on Qingre Jiedu oral liquid against influenza A virus in vivo

目的 观察清热解毒口服液在BALB/c小鼠体内抗甲型流感病毒的作用.方法 将BALB/c小鼠随机均分为正常对照组、流感病毒感染模型组、利巴韦林片组、连花清瘟胶囊组及清热解毒口服液高、中、低剂量组.小鼠感染流感病毒后ig给药,以生存情况、死亡保护率及延长生命率作为指标,观察清热解毒口服液抗流感病毒的作用.结果 清热解毒口服液各剂量组均能减轻感染小鼠的发病症状;死亡保护率为50％ ～ 60％;延长生命率为61.56％～73.84％.与阳性药物利巴韦林片及连花清瘟胶囊比较,差异无统计学意义.结论 清热解毒口服液在BALB/c小鼠体内有抗甲型H1N1流感病毒的作用,其机制有待深入研究.     

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.