老年 COPD 患者奈替米星静脉滴注给药的药动学研究与临床效果分析

目的：研究老年慢性阻塞性肺部疾病（ COPD）患者奈替米星（ NTM）静脉滴注给药在下呼吸道的分布和药物动力学,并分析其临床疗效和不良反应。方法24例COPD患者分为A、B组,每组12例。2组NTM剂量分别为A组每天7=．0 mg／kg,B组给予5．0 mg／kg,静脉滴注。利用荧光偏振免疫方法,使用尿素替代肺泡液稀释内标,测定肺泡液、支气管分泌液和血清中的NTM浓度。结果 A组药物动力学参数表现为,血清中NTM最高浓度Cmax可达（26．73±4．96）mg／L,消除半衰期为3．95 h;肺泡液中最高浓度为（7．75±2．12）mg／L,是血清Cmax的30％,而支气管分泌液中药物的浓度与肺泡液浓度呈正相关（ r ＝0．6434, P ＜0．05）。采用静脉滴注给药方式,肺泡中的药物浓度比常见肺炎致病菌的MIC值高。连续给药7 d后,所有患者均未见神经、肝、肾毒性。结论静脉滴注给药方式,给药间隔时间长,且不会增加不良反应,更适用于临床上老年COPD患者的治疗。     

12例COPD患者奈替米星药动学及其下呼吸道浓度测定

目的:探讨COPD老年患者奈替米星的药代动力学特性及其下呼吸道浓度分布.方法:一天一次静脉滴注奈替米星7mg/kg,以尿素作为肺泡液稀释内标,用荧光偏振免疫法测定血清、支气管分泌液和肺泡液中奈替米星浓度.结果:奈替米星7mg/kg一天一次静脉滴注30min,血清峰浓度26.71±4.95mg/L,消除半衰期3.69h;肺泡液中药物峰浓度7.76±2.13mg/L ,相当于血清峰浓度的29%,两者具有显著相关性(r=0.986),且超过常见肺炎致病菌的MIC 值;支气管分泌液药物浓度与血清峰浓度无相关性(r=0.687).结论:奈替米星一天一次静脉滴注7mg/kg用于COPD老年患者能有效治疗肺部感染.     

12例COPD患者奈替米星药动学及其下呼吸道浓度测定

目的:探讨COPD老年患者奈替米星的药代动力学特性及其下呼吸道浓度分布.方法:一天一次静脉滴注奈替米星7mg/kg,以尿素作为肺泡液稀释内标,用荧光偏振免疫法测定血清、支气管分泌液和肺泡液中奈替米星浓度.结果:奈替米星7mg/kg一天一次静脉滴注30min,血清峰浓度26.71±4.95mg/L,消除半衰期3.69h;肺泡液中药物峰浓度7.76±2.13mg/L ,相当于血清峰浓度的29%,两者具有显著相关性(r=0.986),且超过常见肺炎致病菌的MIC 值;支气管分泌液药物浓度与血清峰浓度无相关性(r=0.687).结论:奈替米星一天一次静脉滴注7mg/kg用于COPD老年患者能有效治疗肺部感染.     

美罗培南在老年肺部感染患者的药动学及疗效观察

用美罗培南 5 0 0mg ,静脉点滴 ,每 12h一次 ,治疗 16例老年肺部感染患者 ,通过细菌培养、检测血药浓度动态变化及支气管肺泡灌洗液 (BAL)中的药物浓度 ,以探讨美罗培南对老年肺部感染患者的适用价值。结果显示 ,致病菌阴转率为 94% ,治疗有效率为 87% ;静滴后 1.5hBAL液中药物浓度为 ( 0 .2 97± 0 .0 6 5 )mg/L ;血药峰值浓度为 ( 2 9.47土 0 .99)mg/L ,用药 8h后血药浓度为 ( 2 .44± 0 .90 )mg/L ,半衰期约为 1h。     

左氧氟沙星在胆汁中的药动学研究

目的研究左氧氟沙星(levofloxacin,LVLX)在胆道手术患者的药动学特点。方法13名施行胆道手术并行T管引流的患者静脉滴注单剂量LVLX 400mg,用高效液相色谱法测定LVLX在不同时相胆汁中的药物浓度。结果LVLX在胆汁中的药动学参数分别为tmax(2.81±1.96)h,cmax(7.08±2.40)mg/L,t1/2(21.24±30.46)h,AUC(55.39±26.07)(h.mg)/L。胆汁药物浓度均超过胆道常见病原菌的MIC,AUC/MIC均大于12。结论广泛的抗菌谱和极高的胆汁药物浓度提示该药是治疗和预防胆道感染的有效药物,单剂量400mg单次给药具有治疗和预防胆道感染的作用。     

亚胺培南西司他丁治疗老年肺部感染的药代动力学观察

目的：观察亚胺培南西司他丁治疗老年肺部感染的药代动力学。方法：选择我院2014年12月～2015年12月收治的92例老年肺部感染患者,随机分为两组,各46例。对照组给予头孢噻肟舒巴坦进行治疗,实验组给予亚胺培南西司他丁进行治疗,对比两组细菌清除率,并检测实验组中7例的血药浓度与8例肺泡灌洗液中亚胺培南西司他丁的浓度。结果：实验组7例肺部感染药代动力学实验表明,峰值浓度为（29.13±0.62）mg/L,半衰期在1h左右;实验组8例静脉滴注亚胺培南西司他丁1.5h肺泡灌洗液中药物平均浓度为（1.45±0.13）mg/L,蛋白含量为（0.21±0.07）g/L,单位蛋白量中药物浓度为（6.71±1.17）mg/g;实验组细菌清除率为93.48%,明显高于对照组的76.09%,差异显著（P＜0.05）。结论：亚胺培南西司他丁血药浓度与细菌清除率均具有较高水平,临床应用价值显著。     

乙基西梭霉素在全胃肠外营养病人的药代动力学

目的观察在全胃肠外营养(TPN)时病人体内乙基西梭霉素(NTM)的药代动力学。方法用高效液相色谱 -间接光度检测(HPLC_IPD)法测定7例行TPN病人和7例对照病人静滴NTM5mg·kg-1 后血清和尿中药物浓度 ,并计算药代动力学参数。结果NTM在体内处置符合二室开放模型 ,静滴后TPN组NTM血清峰浓度低于对照组 ,但无显著性差异 ,至5h后TPN组浓度开始高于对照组 ,至12h时已明显高于对照组 ;尿中原型药物排出率TPN组较对照组下降 ,但无显著性差异 ;TPN组与对照组血清NTM的t1/2(β)分别为(5.8±1,6)h和(3.5±1.4)h。结论病人给TPN时 ,NTM体内分布和消除变慢。     

抗生素对呼吸系统的透入研究

治疗支气管及肺部细菌感染的成功或失败,其重要因素之一是合宜抗生素浓度在呼吸道感染部位的(氵弥)散,多数文献应用动物模型或痰液作为研究手段或标本。本文应用气管插管、气管造瘘或纤维支气管镜等方法以获得不为上呼吸道分泌物或唾液所污染的下呼吸道支气管分泌液。此类标本的测定结果可代表游离药物在肺部的有效浓度、药物的透入速度、在肺部的代谢和分泌液的廓清等因素。采用一次给药后检查380例无肝、肾功能损害的慢性支气管炎患者,在他们继发呼吸道感染时取痰液标本,同时收集给药后不     

Aztreonam的药代动力学及其在支气管分泌物中浓度

本文研究了监护室内患下呼吸道感染的危重病人体内Aztreonam(AZT)的药代动力学,并探讨了在肺部感染时,药物在支气管分泌物中是否达到有效浓度。选女性2名、男性8名,年龄18-77岁,所有病人均需气管插管。3人为支气管炎,7人为支气管肺炎。药物剂量范围15.7-36.4mg/kg,在研究过程中未用其它抗生素。在首次静注(3分钟)AZT 2克后,血清中平均浓度是242.6±140mg/L,在用药后8小时(第2次给药前)是4.4±3.3,尿浓度始终较高,且主要以原药排泄。在用药后2     

加替沙星在老年社区获得性肺炎患者体内的临床药动学研究

目的研究加替沙星在老年社区获得性肺炎患者(community-acquired pneumonia,CAP)体内的药动学特征。据此拟订其用于老年CAP患者的给药方案。方法以HPLC测定患者口服加替沙星片(400 mg)后体内的血药浓度。结果受试者单剂口服400 mg加替沙星片后,体内血液分布符合二室开放模型,血药峰浓度cmax(2.83±1.13)mg.L-1、CL值(10.47±7.60)L.h-1低于健康人群,而达峰时间tmax(3.30±0.93)h、消除半衰期t1/2β(10.1±4.47)h、AUC(6.9±19.5)mg.h.L-1均较健康人群长,个体间参数差异较大。结论在给老年CAP患者使用加替沙星片时应注意给药剂量和给药间隔,慎重给药。     

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.