显齿蛇葡萄总黄酮对兔口腔黏膜溃疡的作用

目的研究显齿蛇葡萄总黄酮抗口腔黏膜溃疡的作用。方法分别采用表皮葡萄球菌或10%乙酸注射到新西兰兔颊黏膜,或用同种异体口腔黏膜匀浆上清液作为免疫抗原注射于兔背部皮下,制备3种口腔黏膜溃疡模型。显齿蛇葡萄总黄酮剂量为84,266和840mg.kg-1,西地碘为1mg.kg-1,每天分4次口腔局部涂布给药3～4d。观察溃疡发生情况和溃疡愈合时间,检查溃疡直径和局部炎症指数,检测抗口腔黏膜抗体滴度和局部病理改变。结果显齿蛇葡萄总黄酮能使表皮葡萄球菌性、乙酸性口腔黏膜溃疡模型的溃疡直径明显缩小,炎症指数降低,愈合时间缩短,并随药物剂量增加作用增强;对免疫性口腔黏膜溃疡,可使溃疡发生率明显降低,抗体滴度下降,局部病理变化明显减轻。结论显齿蛇葡萄总黄酮有减轻口腔黏膜溃疡炎症、促进溃疡愈合的作用。     

灵杏咳喘胶囊体内外抑菌作用的实验研究

目的研究灵杏咳喘胶囊的体内、外抑菌作用。方法采用标准试管二倍稀释法测定灵杏咳喘胶囊的最低抑菌浓度（MIC）,并观察其在小鼠体内对金黄色葡萄球菌和肺炎克雷伯氏菌的抑菌作用。结果体外抑菌试验显示：灵杏咳喘胶囊对肺炎杆菌、金黄色葡萄球菌、肺炎双球菌、大肠埃希氏菌与β-溶血性链球菌均有明显的体外抑制作用,其MIC为0.50～2.0 g.L-1。体内抗菌试验显示：治疗性给药条件下,该药能显著延长肺炎克雷伯氏菌感染小鼠的平均存活时间,预防性给药条件下,不仅能显著提高肺炎克雷伯氏菌感染小鼠的存活率（P〈0.05）,还能使感染小鼠的平均存活时间延长。结论灵杏咳喘胶囊具有一定的体内、体外抑菌作用。     

盐酸头孢他美酯体内和体外抗菌作用研究

目的评价盐酸头孢他美对临床常见致病菌的体外和体内抗菌作用。方法采用试管二倍稀释法测定最低抑菌浓度(MIC),同时与对照药头孢克洛进行对比。结果头孢他美对革兰氏阳性菌如乙型溶血性链球菌、肺炎链球菌有较强的抗茵活性,MIC50均为0.25μg/mL;对革兰阴性菌如淋球菌、肺炎克雷伯杆菌、痢疾杆菌、流感嗜血杆菌也有较强的抗菌活性,MIC50分别为0.25、0.5、0.5和0.5μg/mL。头孢他美酯口服给药对金葡菌、大肠埃希菌感染小鼠有明显的保护作用,其ED50分别为24.6和9.3mg/kg,头孢他美酯对金葡菌的抗菌活性弱于头孢克洛,但对大肠埃希菌的抗菌活性强于头孢克洛。结论头孢他美和头孢他美酯对临床常见致病菌有良好的抗菌作用。     

阿莫西林和哌拉西林抗菌活性的比较

比较阿莫西林和哌拉西林的体外和体内抗菌活性。体外试验采用琼脂二倍稀释法测定最低抑菌浓度(MIC);采用肉汤二倍稀释法测定最低杀菌浓度(MBC);活菌计数法绘制杀菌曲线(KCs);测定培养基pH值、细菌接种量、血清蛋白结合对阿莫西林和哌拉西林抗菌活性的影响;活菌计数法测定抗生素后效应(PAE);测定防耐药变异浓度(MPC)。体内试验采用小鼠的大肠埃希菌及金黄色葡萄球菌全身感染模型,静脉给药保护后测定药物的半数有效量(ED50);采用免疫低下小鼠大腿金黄色葡萄球菌感染模型,观察尾静脉给药24 h后的大腿肌肉感染菌量变化。结果:阿莫西林的MIC90高于哌拉西林,但血清蛋白结合的影响小于哌拉西林;阿莫西林和哌拉西林均对大肠埃希菌和金黄色葡萄球菌全身感染小鼠具有良好的保护作用,阿莫西林的ED50小于哌拉西林;阿莫西林对金黄色葡萄球菌大腿肌肉感染的免疫低下小鼠治疗效果优于哌拉西林。阿莫西林在体外抗菌作用次于哌拉西林,但体内抗菌作用优于哌拉西林。     

盐酸头孢他美酯体内和体外抗菌作用研究

目的评价盐酸头孢他美对临床常见致病菌的体外和体内抗菌作用。方法采用试管二倍稀释法测定最低抑菌浓度（MIC）,同时与对照药头孢克洛进行对比。结果头孢他美对革兰氏阳性菌如乙型溶血性链球菌、肺炎链球菌有较强的抗菌活性,MICso均为0．25μg／mL;对革兰阴性菌如淋球菌、肺炎克雷伯杆菌、痢疾杆菌、流感嗜血杆菌也有较强的抗菌活性,MIC50分别为0．25、0．5、0．5和0．5μg／mL。头孢他美酯口服给药对金葡菌、大肠埃希菌感染小鼠有明显的保护作用,其ED50分别为24．6和9．3mg／kg,头孢他美酯对金葡菌的抗菌活性弱于头孢克洛,但对大肠埃希菌的抗菌活性强于头孢克洛。结论头孢他美和头孢他美酯对临床常见致病菌有良好的抗菌作用。     

硫肽类抗生素诺卡沙星抗革兰阳性菌的活性研究

目的：研究新型硫肽类抗生素诺卡沙星对临床常见革兰阳性致病菌的抗菌活性,探讨其抗菌机制,并与临床常用抗生素进行比较。方法：采用琼脂二倍稀释法测定最低抑菌浓度（Minimal Inhibition Concentration,MIC）,采用微量肉汤二倍稀释法测定最低杀菌浓度（Minimal Bactericidal Concentration,MBC）,采用小鼠体内抗菌保护实验测定体内抗菌活性。结果：诺卡沙星对甲氧西林耐药的葡萄球菌、青霉素耐药的肺炎球菌均显示较强的抗菌活性,对金黄色葡萄球菌MRSA、MSSA,表皮葡萄球菌MRSE、MSSE的MIC50值分别为0.016、0.016、0.0625、0.03125 mg· L-1,对肺炎球菌（PRSP/PISP）、化脓性链球菌、肠球菌的MIC50值为0.008、0.008、0.016 mg·L-1,其MIC50值为万古霉素的1/32-1/128,为莫西沙星的1/4-1/256,为利奈唑胺的1/32-1/256。注射用诺卡沙星经静脉给药后,对金黄色葡萄球菌感染小鼠均呈现体内保护作用,其ED50值明显低于对照药万古霉素和利奈唑胺,体内抗菌保护作用优于对照药。结论：诺卡沙星具有高效抗菌作用,明显优于万古霉素、利奈唑胺及莫西沙星,且与它们之间无交叉耐药现象。     

清喉口含片动物体内、外抑菌实验研究

目的研究清喉口含片的体内、外抑菌作用。方法采用标准试管二倍稀释法测定清喉口含片的最低抑菌浓度(MIC)和最低杀菌浓度(MBC),并观察清喉口含片在小鼠体内对金黄色葡萄球菌的抑菌作用。结果清喉口含片对金黄色葡萄球菌、甲型溶血性链球菌、乙型溶血性链球菌、肺炎链球菌、流感嗜血杆菌均有明显的体外抑制作用,其MIC、MBC分别为0.0625~0.50、0.125~1.0g/ml,对腹腔注射金黄色葡萄球菌的小鼠具有抑菌作用。结论清喉口含片具有体内、外抑菌作用。     

阿扑西林的体内外抗菌作用

目的评价阿扑西林的抗菌作用。方法体外试验采用平皿二倍稀释法测定最低抑菌浓度(MIC),比较药物的90%抑菌范围(MIC90)或者50%抑菌范围(MIC50)。体内试验采用腹腔注射肺炎链球菌、金黄色葡萄球菌、肠球菌、大肠杆菌分别感染小鼠制备模型,尾静脉注射不同浓度的阿扑西林,观察小鼠1周内的死亡情况。结果阿扑西林对苯唑西林敏感的葡萄球菌、肺炎链球菌、肠球菌、非产超广谱β-内酰胺酶的大肠埃希菌、阴沟肠杆菌、产气肠杆菌均具有较强的抗菌活性;阿扑西林对肺炎链球菌、金黄色葡萄球菌、肠球菌、大肠杆菌感染的小鼠均具有明显的体内保护作用,呈剂量-效应关系。结论阿扑西林在体内和体外均具有明显的抗菌活性。     

金鱼连口服液的急性毒性及药效学实验

目的：观察金鱼连口服液的急性毒性反应和体外、体内抗菌作用。方法：给昆明种小鼠以最大给药体积（40mL·kg^-1）灌胃给药，bid，观察金鱼连口服液的急性毒性反应；选用金黄色葡萄球菌和大肠埃希菌2个菌种，采用试管稀释法测定金鱼连口服液的最小抑菌浓度；运用动物体内抗菌实验模型，观察金鱼连口服液体内抗菌作用。结果：小鼠灌胃给药，其最大给药量相当于临床用量（按人体质量60kg计算）的250倍，14d内无异常反应，体质量正常增长。金鱼连口服液对金黄色葡萄球菌和大肠埃希菌均具有显著抑制作用，金黄色葡萄球菌的MIC503.2mg·L^-1，MIC90 12．8mg·L^-1；大肠埃希菌MIC50 6．4mg·L^-1，MIC50 25．6mg·L^-1。结论：金鱼连口服液无急性毒性作用，具有显著杀灭金黄色葡萄球菌和大肠埃希菌作用。     

牛至挥发油体内外抗痢疾杆菌的作用

目的观察牛至挥发油对痢疾杆菌的抑菌和杀菌作用。方法应用宋内痢疾杆菌和福氏痢疾杆菌F2a腹腔感染小鼠，观察牛至挥发油不同时间灌胃给药后对染菌小鼠的保护作用；体外测定该挥发油对痢疾杆菌不同菌群的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。结果牛至挥发油对感染宋内痢疾杆菌、福氏痢疾杆菌F2a的小鼠有保护作用，对痢疾杆菌不同菌群有明显的抑菌和杀菌作用，MIC和MBC分别为50～100 和125～500 mg · mL 1。结论牛至挥发油是一种抗痢疾杆菌感染的有效药物。     

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.