国产阿洛西林体外抗菌活性研究

本文报道国产阿洛西林对1980～1988年重庆地区临床分离的446株致病菌的体外抗菌活性,并与美国Miles 药厂生产的同类产品进行比较。结果表明阿洛西林具有广谱抗菌作用。国产阿洛西林在浓度为32μg/ml时能抑制79.8％的细菌。本品对金葡菌、痢疾杆菌、变形杆菌和绿脓杆菌的MIC_(50)和MIC_(90)各为2和16、2和 4,4和32、8和64μg/ml。阿洛西林对其他革蓝氏阴性杆菌和粪链球菌亦具较好抗菌活性。其抗绿脓杆菌的作用较羧苄青霉素为强.阿洛西林对庆大霉素和羧苄青霉素耐药绿脓杆菌的抑菌率各为81.7％和85％。     

阿洛西林在狗的药物动力学参数的反相高效液相色谱法测定

本文用反相高效液相法测定犬静注和肌注阿洛西林20mg/kg后的血中药物浓度,并据此计算有关药物动力学参数。ODS-C_(18)为固定相,甲醇/67mmol/L磷酸缓冲液(1:1,vol/vo1)为流动相,紫外(uv)检测。以对硝基丙酰苯胺为内标物对血清中阿洛西林进行定量测定。根据F值,r 2/1值和AIC(Akaike's Information Criterion)值判断静注和肌注药物后在体内的转运过程分别符合开放型二室和一室模型。静注后即刻血药浓度为218±13μg/mL,T_(1/2α)为0.13h。肌注后T_(max)和T_(1/2ka)分别为0.75和0.24h,C_(max)为16±6μg/mL,但im后AUC仅为iv相同剂量后的38％。该药iv和im后的T_(1/2)分别为1.5和1.7h,V_d分别为0.35和0.43L/kg。本实验结果与微生物法测定结果间无显著差异。     

国产阿洛西林体外抗菌作用研究

本文报道国产阿洛西林对临床分离的372株革蓝氏阳性、阴性菌的体外抗菌作用。阿洛西林在12.5μg/ml时能抑85％金葡球菌、90％粪链球菌以及所试全部的链球菌;在此浓度下,能抑制85％大肠杆菌、79％绿脓杆菌、85％奇异变形杆菌、68％吲哚阳性变形杆菌、67％产碱杆菌。对本试验所试绿脓杆菌的作用比美洛西林、羧苄青 素强,但不如哌拉西林强。阿洛西林对羧苄青霉素耐药的绿脓杆菌较敏感。除了绿脓杆菌外,阿洛西林对肠细菌科其他各菌株也有较好的活力,但均不如美洛西林强。     

高效液相色谱法测定血浆中阿司匹林和水杨酸

应用0072％磷酸-甲醇(45:55,v/v)为流动相,在μ-Bondapark C18柱上,以苯甲酸为内标,建立了家兔血浆中阿司匹林(1)和水杨酸(2)的高效液相色谱测定法。1和2平均绝对回收率分别为100.7和104.8％,变异系数分别为5.6和7.3％。1.2的血浆浓度分别在2～10μg/ml、20～100μg/ml范围内呈良好线性关系。     

高效液相色谱法测定人血浆中舒乐安定的浓度

本文应用高效液相色谱法测定人血浆中舒乐安定的浓度。检测波长为240nm,利眠宁为内标,甲醇:磷酸盐缓冲液为移动相。回收率为97.3～108.9%,日内和日间误差(浓度0.60μg/ml)(CV)分别为2.5%和2.9%(n=9)。对临床数十名患者血浓测定,其血浓在0.4～0.87μg/ml,为临床合理用药提供了依据。     

国产阿洛西林体外抗菌作用研究

氨苄西林、羧苄西林的应用使青霉素的抗菌谱已扩大了包括革蓝氏阴性杆菌,临床使用已证明这二药的疗效,但药菌谱窄及随着高剂量的使用而出现毒副反应而限制了它们的使用。临床上虽有一定数量的新青霉素在使用,仍需要有抗菌谱广,特别对绿浓杆菌有作用的新青霉素,阿洛西林是具有这一特点的新青霉素,国产阿洛西林已由四川抗菌素工业研究所研制成功。本文报道国产阿洛西林对临床分离的14种172株革蓝氏阳性、阴性菌的体外抗菌作用,并与其它青霉素类抗生素进行比较。实验结果表明新的脲基青霉素——阿洛西林为一广谱抗生素。在12.5μg/ml时,阿洛西林能抑制85％金黄色     

人血中茶碱浓度高效液相色谱法测定的改进

本文应用高效液相色谱法测定人血中茶碱的浓度。以甲醇水（30∶70V／V）作流动相，乙腈为提取剂，巴比妥钠作内标；线性范围在5～100μg／ml，相关系数r=0.9997；最低检测限1.0μg／ml；平均回收率为94.81±5.93％；日内误差（CV％）和日间误差（CV％）分别为4.6％和5.9％。应用本法对哮喘病人氨茶碱用药进行监测，为临床治疗及个体给药提供依据。     

HPLC法测定机体中巴比妥酸盐类

在临床上或意外事故中常需对病人体液或组织中的巴比妥酸盐类进行测定,但过去的测定方法都不理想.本文用HPLC法对12种常用巴比妥酸盐进行定性或定量测定,方法快速、灵敏、复演性好.作者用μBondapak C_(18)柱子(15cm×3.9mm,id)测定血浆、尿、死者血液和组织中的巴比妥酸盐,该法已正式用于法庭和临床毒理学分析.材料:1mg/ml巴比妥酸盐甲醇液,血浆和血液的工作液(100和10μg/ml)用甲醇稀释;巴比妥酸盐标准液浓度分别为1、2、5、10、20、50和100μg/ml.50μg/ml阿普巴比妥和1mg/ml酚酞的甲醇液为内标.     

美洛西林钠的HPLC测定

建立了测定美洛西林钠的HPLC法.采用Shim-packCLC-ODS为色谱柱,甲醇-0.05mol/L磷酸二氢钠溶液-10%氢氧化四乙基铵溶液-水(403∶200∶3∶394,用磷酸调节pH值至5.5±0.1)为流动相,流速1.0ml/min,检测波长230nm.美洛西林钠在200～1995μg/ml浓度范围内其峰面积与浓度呈良好线性关系,r=0.9999.方法平均回收率为99.29%,RSD0.41%.     

HPLC法测定人血清中头孢呋肟浓度

本文建立了快速、简便测定人血清中头孢呋肟反相HPLC法,采用5×20mn不锈钢柱内填10um YWG-C_(18)H_(37)17定相,流动相甲醇:水:冰醋酸(28:71:1v/v),流速1.2ml/min,以头孢噻肟为内标物,紫外检测波长290nm,用10％三氯醋酸作蛋白沉淀剂,与血清之比为1:2(v/v)。头孢呋肟的日内回收率为100.34±6.60％,日间回收率为99.69±6.33％。头孢呋肟最低检测限为2ng,最低检测浓度为0.2μg/ml。在0.25～10μg/ml浓度范围内线性良好,相关系数r=0.9999。     

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.     

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.     

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.