萘替米星与妥布霉素治疗耐药型下呼吸道细菌感染的比较

目的：探索奈替米星治疗耐药型下呼吸道细菌感染的疗效。方法：奈替米星组４２例（男性２４例，女性１８例；年龄６０±ｓ１１ａ）。用奈替米星２００ｍｇ加入０．９％氯化钠注射液２００ｍＬ中静脉滴注，ｑｄ。妥布霉素组３６例（男性２１例；女性１５例；年龄５８±１１ａ）。用妥布霉素８０ｍｇ，加入０．９％氯化钠注射液２００ｍＬ中静脉滴注，ｂｉｄ。疗程均为１０～１４ｄ。结果：奈替米星组痊愈８２％，显效１２％，总有效率９４％。妥布霉素组痊愈５３％，显效２３％，总有效率７７％。结论：奈替米星组与妥布霉素对治疗耐药型下呼吸道细菌感染均有效，奈替米星治疗优于妥布霉素，经χ２检验Ｐ＜０．０５，且无副作用     

硫酸奈替米星注射液临床疗效及药效学研究

使用国产硫酸奈替米星注射液治疗呼吸系统和泌尿系统感染共63例．临床有效率为98．4％，细菌阴转率和细菌清除率均为98．3％，不良反应发生率为9．1％。同时用庆大霉素随机对照治疗泌尿系统感染35例，奈替米星的临床疗效和细菌学疗效明显优于庆大霉素（P＜0．05），但不良反应发生率两者之间无显著性差异（P＞0.05）。体外药敏试验结果表明奈替米星的药物敏感率大于阿米卡星和庆大霉素，77．3％庆大霉素耐药菌和92．9％环丙沙星耐药大肠杆菌对奈替米星敏感，国产奈替米星的体外抗菌活性与进口产品相同。     

国产阿齐红霉素胶囊的临床验证小结

国产阿齐红霉素进口同类品随机对照治疗呼吸道感染３２例（各组均为１６例）结果表明，国产品组的有效率为９３．８％（１５／１６），痊愈率为５６．２％（９／１６）；进口品组的有效率为８７．５％（１４／１６），痊愈率为６２．５％（１０／１６），两组无显著性差异（Ｐ＞０．０５）。两组的细菌清除以菌株数计及以病例数计，分别为９３．３％（１４／１５）和８５．％（１２／１４），无显著性差异（Ｐ＞０．０５）。两组出现     

头孢拉定对奈替米星药代动力学的影响

目的 观察头孢拉定对奈替米星药代动力学的影响。方法１４例感染患者随机分成单用奈替米星组（ＮＴＭ）和奈替米星＋头孢拉定组（ＮＴＭ＋ＣＰＲ）。采用高效液相色谱一间接光度检测（ＨＰＬＣ－ＩＰＤ）法，测定患者单剂量静脉滴注 ５ ｍｇ ＮＴＭ后的血清药物浓度，并计算主要药动学参数；同时测定尿液药物浓度及药物回收率。结果ＮＴＭ组和ＮＴＭ＋ＣＰＲ组的Ｔ１／１／２β分别为２．４０±１．０１ｈ和 ４．３３± １．４３ｈ（Ｐ＜ ０．０１），ＡＵＣ０～２４ｈ６３．４２± ３０．００ｍｇ／Ｌ·ｈ和 ７８．５４± ３２．８８ｍｇ／Ｌ·ｈ（ｐ＜ ０．０ １），２４ｈ尿中 ＮＴＭ Ｗ收率也有显著性差异。结论 ＮＴＭ＋ＣＰＲ联用时 ＮＴＭ生物利用度增高，尿中回收率下降，连续长期联用将导致体内蓄积。     

洛美沙星治疗淋病临床疗效对比观察

观察了国产洛美沙星与氧氟沙星随机对照治疗无合并症淋病１０１例的临床疗效及不良反应。洛美沙星组５８例，氧氟沙星组４３例。男性病人８７例服用洛美沙星或氧氟沙星２００ｍｇ，每日２次，２天；女性病人１４例服４００ｍｇ，每日２次，２天。两药临床治愈率分别为９３．１％（５４／５８）和９０．７％（３９／４３），无显著性差异（Ｐ＞０．０５）。细菌清除率分别为９６．６％（５６／５８）和９３．０２％（４０／４３）。其不良反应发生率分别为１．７％（１／５８）和２．３％（１／４３），反应轻微。洛美沙星、氧氟沙星、环丙沙星、头孢曲松、青霉素和大观霉素对５６株淋球菌的ＭＩＣ＿（５０）／ＭＩＣ＿（９０）（ｍｇ／Ｌ）为０．０６／０．２５、０．０６／０．１２５、０．０６／０．１２５、０．０６／０．２５、０．５／１．０和１６／３２。     

奈替米星体液浓度测定的方法学研究

通过对国产硫酸奈替米星注射后人体血尿中药物浓度测定，建立了奈替米星体液浓度测定的微生物法，该方法的检测限为０．０３７５～０．０７５１μｇ，最低检测浓度为０．２５～０．５μｇ／ｍｌ，回收率为８８．８％±３．６３％～９８％±１４．４０％，重复性试验相对标准差为２．２２％～５．３４％；并对１０例健康受试者用药后血标本１００余份进行了微生物法测定和高压液相色谱法测定，对两种方法测定结果的比较发现：微生物法测定的血药浓度明显高于ＨＰＬＣ法（Ｐ＜０．０１），而ＨＰＬＣ法由于需复杂的样品预处理和特殊的色谱条件，测定的血药浓度较低，回收率仅７１．９８％～７６．９６％。不过，两种方法测定结果的相关性较好。本研究结果提示：微生物法测定奈替米星体液浓度简便、易操作、结果准确可信，适用于体液药物浓度测定。     

奈替米星配伍甲硝唑治疗及预防阑尾炎及阑尾术后感染

目的：观察奈替米星（Ｎｅｔ）配伍甲硝唑（Ｍｅｔ）治疗阑尾炎及预防阑尾术后感染的效果及Ｎｅｔ在阑尾组织中的分布。方法：确诊阑尾炎病人给予Ｎｅｔ（０．３ｇ,ｉｖ ｇｔｔ,ｑｄ）／Ｍｅｔ（０．５ｇ,ｉｖ ｇｔｔ,ｔｉｄ）２￣７ｄ保守治疗或阑尾切除手术病人术前１次及术后２ｄ应用Ｎｅｔ／Ｍｅｔ预防阑尾术后感染。结果：１４例阑尾炎保守治疗有效率为６４．３％（９／１４）。５２例阑尾切除术总手术感染率为１．９％（     

国产硫酸奈替米星注射液的药动学研究

采用微生物法对８名健康受试者单剂静脉滴注和肌注１００ｍｇ硫酸奈替米星注射液进行药动学研究，测定了给药后不同时间的血、尿药浓度，并经计算机程序计算药动学参数。结果显示：单剂静滴和肌注后的药动学符合二室开放模型，静滴药动学方程式为：Ｃ＝１０．８１２２ｅ－３．６７１４ｔ＋４．８８３１ｅ－０．２２０５ｔ；肌注药动学方程式为：Ｃ＝９．６８６８ｅ－１．４９１８ｔ＋５．４７５４ｅ－０．２０８６ｔ－１０．９７７０ｅ－３．７２５９ｔ。Ｔ１／２α分别为０．７４７８和０．４１２１ｈ，Ｔ１／２β分别为３．２３０８和２．８７４０ｈ，峰浓度分别为１３．１１和７．６０μｇ／ｍｌ，肌注后达峰时间为０．４８ｈ，总清除率分别为３．２２和３．２６（Ｌ／ｈ），２４ｈ肾排出率分别为５９．０６％和６８．５７％。给药后６ｈ内血药浓度及２４ｈ内尿药浓度＞１μｇ／ｍｌ，尿药浓度明显高于血药浓度。本研究结果与进口硫酸奈替米星注射液药动学过程基本一致。根据其药动学特征，建议一般给药方案为１００ｍｇ每日２次，可达到和维持有效血药浓度。     

β—七叶皂苷钠治疗流行性乙型脑炎疗效观察

１１６例流行性乙型脑炎（乙脑）病人分为治疗组６２例（男３９例，女２３例；平均年龄５．１岁）在常规治疗的同时加用β－七叶皂苷钠成人１０ｍｇ，儿童０．１～０．２ｍｇ／ｋｇ，加入０．９％氯化钠１００～２００ｍｌ静脉滴注，８ｄ至恢复期，与仅按常规治疗的５４例（男３４例，女２０例；平均年龄５．３岁）作对照。结果：治疗组治愈率与总有效率为８２．３％与９１．９％，优于对照组的６４．８％与７５．９％，Ｐ＜０．０５或Ｐ＜０．０１；病死率３．２％，低于对照组的１４．８％；抽搐停止时间，神志转清时间及呼吸衰竭纠正时间较对照组缩短，Ｐ＜０．０１或Ｐ＜０．０５；病情加重率（１．６％）低于对照组（１４．８％），Ｐ＜０．０５，提示β－七叶皂苷钠是治疗乙脑的有效药物。     

氟氧头孢与头孢美唑随机对照治疗细菌性感染的临床评价

氟氧头孢（ＦＭＯＸ）为一新的氧头孢烯类广谱抗生素。我们以头孢美唑（ＣＭＺ）作为对照药，进行随机对照临床试验，共治疗细菌性感染６４例，其中试验组与对照组各３２例，包括上、下呼吸道感染３０例、泌尿道感染１８例、妇科感染５例及外科感染１１例，以评价其安全性和有效性。试验药与对照药均静脉给药，每次１～２ｇ，每日２次，疗程７～１４天。试验组与对照组总有效率分别为９３．８％和９０．６％；细菌清除率分别为８８．９％和９１．４％；均无统计学显著差异（Ｐ＞０．０５）。临床分离７１株致病菌药敏试验结果表明：８４．５％对ＦＭＯＸ高度敏感，８３．３％的金葡球菌（包括ＭＲＳＡ）对ＦＭＯＸ高度敏感。试验组与对照组不良反应发生率分别为６．０６％和９．３８％，无统计学显著差异（Ｐ＞０．０５）。以上结果表明ＦＭＯＸ治疗临床各系统感染，特别对金葡球菌感染安全有效     

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.

---

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.     

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.