多药联合治疗老年细菌性下呼吸道感染的对照观察

目的：评价头孢哌酮,舒巴坦和头孢哌酮,舒巴坦加头孢克洛序贯疗法治疗老年细菌性下呼吸道感染的临床疗效及成本效果分析。方法：将75例老年细菌性下呼吸道感染患者随机分为治疗组和对照组,治疗组予头孢哌酮,舒巴坦2g静滴,然后给予头孢克洛250mg,po,bid;对照组予头孢哌酮,舒巴坦2g静滴,bid,治疗组和对照组均治疗8～10d。结果：对照组和治疗组痊愈率分别为62．1％和63．2％,总有效率分别为91．9％和92．1％,治疗后细菌清除率分别为84．8％和86．6％;两组以上结果差异均无统计学意义（P〉0．05）。序贯疗法整个疗程平均节省1193元。结论：头孢哌酮／舒巴坦加头孢克洛序贯疗法治疗老年细菌性下呼吸道感染．临床疗效显著,比单用头孢哌酮／舒巴坦更具成本效果,患者依从性好。     

头孢吡肟、头孢哌酮／舒巴坦与美罗培南治疗成人下呼吸道感染的成本-效果评价

目的：评价头孢吡肟、头孢哌酮／舒巴坦与美罗培南治疗成人下呼吸道感染的临床疗效及经济学意义。方法：80例下呼吸道感染患者随机分为3组,分别给予头孢吡肟、头孢哌酮／舒巴坦、美罗培南进行抗感染治疗,统计分析3组临床疗效、细菌学效果及安全性,并进行成本-效果分析。结果：3组临床有效率分别为96．4％、92．6％、96．0％,差异无统计学意义（P〉0．05）;细菌清除率分别为78．6％、77．8％、80．0％,差异无统计学意义（P〉0．05）;不良反应发生率分别为14．3％、11．1％、8．0％,差异无统计学意义（P〉0．05）;组间治疗成本的高低与治疗药物成本的变化密切相关,成本．效果比（C／E）分别为71．4、66．1、75．1,头孢吡肟、美罗培南相对于头孢哌酮／舒巴坦的增量成本-效果比（AC／AE）分别为200．3、317．6。结论：头孢哌酮／舒巴坦是最具成本-效果的治疗下呼吸道感染药物。     

三种头孢菌素治疗下呼吸道感染的成本与效果分析

目的对头孢噻肟、头孢哌酮舒巴坦和头孢唑肟3种用药方案进行成本．效果分析。方法将113例下呼吸道感染的患者按用药情况分为3组,头孢噻肟组：头孢噻肟钠2．0g加入250ml0．9％氯化钠注射液中静脉滴注;头孢哌酮舒巴坦组：头孢哌酮舒巴坦钠2．0g加入250ml0．9％氯化钠注射液中静脉滴注;头孢唑肟组：头孢唑肟钠2．0g加入250ml0．9％氯化钠注射液中静脉滴注,均为2次／d,疗程均为7～14d,进行成本效果分析。结果头孢噻肟组有效30例（83．33％）,头孢哌酮舒巴坦组有效33例（84．62％）,头孢唑肟组有效32例（84．21％）;3组药物细菌清除分别为头孢噻肟组为29株（90．63％）,头孢哌酮舒巴坦组33株（94．29％）,头孢唑肟组31株（91．18％）;3组细菌敏感率分别为头孢噻肟组78．22％,头孢哌酮舒巴坦组84．16％,头孢噻肟组80．20％。3种头孢菌素临床疗效细菌清除率和敏感率的差异均无统计学意义（P〉0．05）;3种头孢菌素成本分别为头孢噻肟组190．08元、头孢哌酮舒巴坦组898．04元和头孢唑肟组1827．32元,3组成本差异有统计学意义（P〈0．05）;成本一效果比为头孢噻肟组2．28、头孢哌酮舒巴坦组10．61和头孢唑肟组21．70。结论临床治疗下呼吸道感染时,头孢噻肟是一个较为有效、经济、合理的选择。     

阿莫西林钠/舒巴坦钠治疗急性细菌性感染的多中心临床研究

为评价阿莫西林钠／舒巴坦钠治疗急性细菌性感染的有效性和安全性，本文以氨苄西林钠／舒巴坦钠为对照，采用多中心随机对照临床试验治疗急性细菌性感染151例，随机分组试验组58例、对照组55例、开放试验组38例。阿莫西林钠／舒巴坦钠每日4．5－6．0g、氨苄西林钠／舒巴坦钠每日4．5－12．0g，两药均分次静脉滴注，疗程7－14d。研究结果表明，试验组与对照组的痊愈率和有效率分别为75．86％与80．00％（P＞0．05）和94．83％与98．18％（P＞0．05），两组细菌产酶率分别为67．35％与69．57％（P＞0．05）；细菌清除率分别为93．88％与95．65％。开放组痊愈率、有效率、细菌产酶率和清除率分别为78．95％、97．37％、63．64％和96．97％。各组均未见严重不良反应。五种药物体外抗菌活性测定表明，阿莫西林钠／舒巴坦钠的抗菌活性与氨苄西林钠／舒巴坦钠、头孢哌酮和头孢曲松相似，明显强于阿莫西林。以上结果提示，阿莫西林钠／舒巴坦钠治疗急性细菌性感染临床疗效确切，使用安全。     

利复星静脉与片剂序贯治疗中度下呼吸道感染疗效和成本效益分析

目的：进一步讨论“利复垦（左旋氧氟沙星）针剂静脉滴注－片剂口服序贯治疗”对中度社区肺部细菌感染的疗效、安全性及卫生经济学的综合评价。方法；采用区组随机化、多中心平行对照试验设计。A组用利复星200mg，静脉滴注，bid;B组先用利复星注射液200mL静脉滴注,bid，连续4d后，改为利复星200mg,po,bid，总疗程均为10－14d。结果；2组总有效率分别为86．79％和84．91％，统计学上无显著性差异（P＞0．05），2组细菌清除率分别为77．78％和76．00％，统计学上无显著性差异（P＞0．05）。2组的不良反应均相似，且很低，未见引起肝、肾功能异常改变。在药物经济学上，B组各项指标均占优势，住院天数明显缩短，住院费用分别为565．53和395．30元，总医疗费分别为3812．38和2452．67元。成本－效果比，2组分别为4394和2889元，经统计学分析，均有显著性差异（P＜0．01）。结论：利复星具有良好的药代动力学和安全性，抗菌谱广，疗效显著，利复星针剂静脉滴注－片剂口服序贯治疗呼吸系统中度细菌性感染，是一理想、成本效果上佳的治疗方案。     

头孢哌酮与头孢哌酮／舒巴坦不良反应的回顾性调查分析

目的：调查比较使用头孢哌酮和头孢哌酮／舒巴坦患者不良反应的发生情况。方法：从解放军药品不良反应监测中心数据库中筛选2001年1月至2006年12月，应用头孢哌酮和头孢哌酮／舒巴坦静脉滴注发生不良反应的病例报告220例。分为2组：头孢哌酮组115例，头孢哌酮／舒巴坦组105例。分别给予头孢哌酮1．0g，头孢哌酮／舒巴坦2．0g（头孢哌酮：舒巴坦=1：1），均溶于5％葡萄糖或0．9％氯化钠注射液100～200ml中，2次／d静脉滴注，滴注时间30～60min，回顾性比较2组不良反应的类型、临床表现、严重程度、转归、对原患疾病的影响及发生时间等方面的差异。结果：2组的主要不良反应相同，均为皮肤及其附件损害、过敏反应及胃肠道反应，其发生率的差异无统计学意义（P〉0．05），2组不良反应转归和对原患疾病的影响不同，头孢哌酮组致死或严重（有后遗症）不良反应的。构成比较头孢哌酮／舒巴坦组高，分别为0．9％、0和2．6％、0头孢哌酮组不良反应出现时间为（1．9±2．1）d，头孢哌酮／舒巴坦组的出现时间较晚，为（2．9±4．1）d．头孢哌酮／舒巴坦组出现4例视觉异常、1例血糖升高和1例声音嘶哑患者。结论：头孢哌酮与头孢哌酮／舒巴坦的主要不良反应相似；头孢哌酮／舒巴坦的安全性更好，但应注意其引起的某些特殊不良反应。     

国产非洛地平片治疗高血压的研究

采用单盲、2：1随机临床对照研究观察八周国产非治地平片的降压效果和毒副反应。167例轻中度高血压者经二周观察期的安慰剂洗脱后，113例非洛地平组（非组，5mg一日二次），54例尼群地平组（尼组，10mg一日二次），血压分别为161／102和159／10lmmHg。结果示；非组血压下降31／21mmHg，较尼组24／17mmHg显著（P＜0．01）、达到目标血压（≤140／90mmHg）者分别占80．5％和63．0％（P＜0．05）。非组显效率和总有效率分别为93．8％和99．1％，也显著高于尼组（72．2％和88．9％，P＜0．01）。治疗后心率均有轻度增加。两组副反应轻微，均无明显代谢性参数的影响。     

头孢哌酮舒巴坦钠对医院获得性肺炎21例疗效观察

目的探讨头孢哌酮舒巴坦钠对医院获得性肺炎的疗效。方法将42例医院获得性肺炎患者随机分为两组，治疗组和对照组各21例，治疗组应用舒巴坦／头孢哌酮2g，静脉滴注，每8～12h 1次；对照组应用头孢哌酮2g，静脉滴注，每8～12h1次。两组疗程均为7—14d。结果头孢哌酮舒巴坦钠有效率为85．7％，头孢哌酮有效率为52．3％，两组比较差异有统计学意义（P〈0．05）。两组患者共分离出病原菌38株，药敏试验显示对头孢哌酮舒巴坦钠敏感率为89．5％，高于头孢哌酮63．2％，差异有统计学意义（P〈0．05）。结论舒巴坦／头孢哌酮对医院获得性肺炎有良好疗效。     

舒巴坦／头孢哌酮与头孢噻肟阴机对照多中心临床研究

目的：用舒巴坦／头孢哌酮与头孢噻肟随机治疗各种中、重度急性细菌性研究,评价前者的安全性及有效性。方法：多中心区组随机平行试验及开放试验,舒巴坦／头孢哌酮（1：1）4－8g/d,分2－4次静滴,7－14d;头孢噻肟4－8g/d,用法同上。结果：共完成167例（试验组60例,对照组61例,开放组者46例）,不同感染病种者试验组痊愈率和有效率 为81．7％和93．3％,对照组者为67．2％和90．2％,开放组者的80．4％和95．6％,无显著性差异（P＞0．05）。试验组和开放组共106例,两组总的痊愈率和有效率分别为81．1％和94．3％。不同细菌感染者各组药物疗效与不同感染病种临床疗效一致。三组细菌培养阳性率分别为90．0％、95．2％及87．0％,细菌β－内酰胺酶产生率分别为66．7％、58．6％及67．5％,细菌清除率（阴转率）分别为98．2％（98．2％）、96．6％（96．4％）与95．0％（94．8％）,无显著性差异（P＞0．05）。纸片敏试结果显示临床分离菌对舒巴坦／头孢哌酮高敏率为96．7％,高于头孢噻肟67．1％、头孢哌酮60．5％、头孢曲松60．5％、头孢他啶77．6％及头孢唑林44．1％,有显著性差异（P＜0．05）。舒巴坦／头孢哌酮的MIC值较其它头孢菌素类低。各组不良反应率分别为6．6％、1．6％及2．2％,试验组表现皮疹、瘙痒、瘀斑（PT延长）及恶心呕吐各1例,对照组ALT、AST升高1例,开放组皮疹1例。结论：结果提示舒巴坦／头孢哌酮 为治疗细菌感染性疾病安全有效的药物。     

头孢哌酮舒巴坦钠治疗社区获得性肺炎临床效果观察

目的：观察头孢哌酮舒巴坦钠治疗社区获得性肺炎（ CAP）的临床效果。方法将80例CAP患者随机分为观察组和对照组各40例。观察组应用头孢哌酮舒巴坦钠治疗,对照组应用左氧氟沙星治疗,比较2组临床疗效、症状体征改善情况和致病菌清除率。结果治疗7d后,观察组总有效率为95．00％明显高于对照组的92．25％,差异有统计学意义（P＜0．05）。观察组患者临床症状体征改善时间明显短于对照组,差异均有统计学意义（P＜0．05）。观察组患者致病菌清除率明显高于对照组,差异有统计学意义（P＜0．05）。结论头孢哌酮舒巴坦钠治疗CAP临床疗效满意,致病菌清除率高,安全可靠,值得临床推广应用。     

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.     

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.     

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.