替加色罗联合多潘立酮治疗餐后不适综合征型功能性消化不良临床观察

目的探讨替加色罗联合多潘立酮治疗餐后不适综合征型功能性消化不良（PDS—FD）的疗效。方法PDS—FD患者161例，采用完全随机设计方法分为3组：多潘立酮组53例给予多潘立酮10mg，2次／d；替加色罗组54例给予替加色罗3mg，2次／d；联合用药组54例给予替加色罗、多潘立酮联合用药进行治疗。计算治疗前1周及治疗第4周患者餐后上腹胀、早饱感、餐后恶心、过度嗳气的症状积分和治疗有效率。结果3组患者治疗第4周各项症状的单项积分较治疗前1周均呈下降趋势（P〈0．01）；联合用药组单项症状积分下降值和治疗有效率均超过多潘立酮组和替加色罗组（P〈0．05）；替加色罗组单项积分下降值（嗳气除外）均超过多潘立酮组（P〈0．05）。结论替加色罗联合多潘立酮对改善PDS—FD单项症状和治疗有效率优于单独应用多潘立酮或替加色罗。     

替加色罗与莫沙必利治疗糖尿病胃轻瘫疗效比较

目的：比较替加色罗与莫沙必利治疗糖尿病胃轻瘫的疗效。方法：65例糖尿病胃轻瘫患者随机分为治疗组（33例）及对照组（32例）。两组均予控制饮食、适宜运动,同时注射胰岛素或口服抗糖尿病药控制血糖。在此基础上,治疗组加用替加色罗片6 mg,po bid,对照组加用莫沙必利片5 mg,po tid。均为饭前30 min口服。两组疗程均为4周。观察两组4周后临床疗效及治疗后6个月、1年的复发率。结果：治疗4周后,治疗组总有效率为93.94%,明显优于对照组总有效率71.88%（P〈0.05）。治疗组6个月和1年的复发率也明显低于对照组（P〈0.05）。结论：替加色罗治疗糖尿病胃轻瘫临床疗效较好,明显降低复发率。     

小剂量替加色罗联合阿米替林治疗便秘型肠易激综合征

目的：观察小剂量替加色罗联合阿米替林对便秘型肠易激综合征（C-IBS）的疗效及耐受性。方法：将60例C—IBS患者随机分为观察组和对照组,对照组给予常规剂量替加色罗口服,观察组给予小剂量替加色罗联合阿米替林口服,疗程均为4周。观察两组治疗后腹痛、腹涨、便秘等症状变化。结果：观察组腹痛、腹泻症状改善较对照组显著,便秘改善两组间差异无统计学意义。对照组不良反应发生率较观察组显著。结论：对便秘型肠易激综合征采用小剂量替加色罗联合阿米替林治疗是安全有效的。     

氯波必利联合黛力新治疗功能性消化不良疗效观察

目的评价氯波比利联合黛力新治疗功能性消化不良（FD）的疗效。方法将98例FD患者随机分为2组。观察组52例,给予氯波必利5mg,3次／d,黛力新片10．5mg,1次／d;对照组46例,给予氯波必利5mg,3次／d。疗程均为4周,比较2组一晦床症状变化。结果2组用药4周后临床主要症状均明显缓解（尸〈0．05或〈0．01）;除恶心、呕吐和上腹部疼痛外,其他症状消失率观察组均优于对照组（P〈0．0）。观察组总有效率92．3％,对照组76．1％,2组比较,差异有统计学意义（P〈0．05）。2组均无严重不良反应。结论氯波比利联合黛力新治疗FD疗效满意,安全性好,是治疗FD的可行方案。     

孟鲁司特联合布地奈德治疗毛细支气管炎的临床疗效观察

目的：观察口服盂鲁司特联合布地奈德雾化吸入治疗毛细支气管炎的疗效。方法：将临床确诊为婴幼儿毛细支气管炎的90例患儿随机分为试验组48例和对照组42例,另选择健康体检儿40例作为正常对照组。对照组给予常规治疗,试验组在常规治疗基础上病初即给予孟鲁司特口服,≤6个月2mg／d,〉6个月4mg／d,睡前顿服,同时给予布地奈德混悬液1mL／次,每日2次雾化吸入,直到临床症状消失后停用,继续口服孟鲁司特1周停用。观察两组治疗后主要临床症状和体征消失时间、住院天数及治愈率,两组治疗前后外周血IgE、IL-4、Eos的变化并与正常对照组比较。结果：试验组有效率91．7％,对照组有效率69．0％,两组比较差异有统计学意义（χ^2=7．48,P〈0．01）。试验组在缓解喘憋、咳嗽、肺部哆音、心率及缩短住院时间等方面均优于对照组（P〈0．05）;治疗后试验组外周血IgE、IL-4、Eos水平均较治疗前明显下降（P〈0．01）,且试验组较对照组下降明显（P〈0．05）。结论：孟鲁司特与布地奈德联合治疗毛细支气管炎,能显著提高疗效,降低药物不良反应发生率,值得在临床应用和推广。     

盐酸依托比利治疗功能性消化不良临床应用

目的观察盐酸依托比利治疗功能性消化不良（FD）的临床疗效及安全性。方法将100例FD患者随机分为治疗组60例,给予盐酸依托比利分散片50mg,3次／d,三餐前30min服;对照组40例,给予多潘立酮片10mg,3次／d,饭前30min服;疗程均为4周。结果盐酸依托比利治疗组总有效率为100％,疗效优于多潘立酮对照组（80％）,P〈0．05。结论盐酸依托比利能明显缓解FD患者症状,不良反应轻,是FD的有效治疗药物。     

氟哌噻吨美利曲辛片治疗功能性消化不良伴抑郁患者的疗效观察

目的评价氟哌噻吨美利曲辛片治疗FD伴抑郁患者的疗效。方法随机将42例FD伴抑郁症病人分为两组，对照组按不同分型给予H2受体阻滞剂和促动力药常规治疗，治疗组在上述常规治疗的基础上每天加用氟哌噻吨美利曲辛片10．5mg bid，疗程3周至6周。结果治疗后两组患者消化道症状均有显著改善（P〈0．05），但治疗组较对照组症状改善更明显（P〈0．05）。治疗组较对照组3周末、6周末SDS评分均有明显降低．差异显著（P〈0．01）；治疗组3周末、6周末SDS评分均有明显降低，差异显著（P〈0．05）；而对照组3周末、6周末SDS评分降低不明显，无显著差异（P〉0．05）。结论氟哌噻吨美利曲辛片治疗FD伴抑郁患者有明显的疗效及良好的安全性．     

培哚普利/吲哒帕胺复合制剂治疗高血压患者的多中心、随机、双盲对照研究

目的：比较低剂量培哚普利／吲哒帕胺复合制剂与吲哒帕胺缓释剂治疗高血压患者血压的变化和治疗反应率及其安全性。方法：共入选原发性高血压病患者231例。经2周安慰剂洗脱期后，分为试验组（n=116）和对照组（n=115）。完成试验患者210例，符合方案分析集（PPS）203例，其中试验组107例，对照组96例。2组随机双盲接受培哚普利2ms／吲哒帕胺0．625mg或吲哒帕胺缓释剂（纳催离SR）1．5mg，qd；治疗6周后，如果舒张压（DBP）〈90mmHg，继续上述治疗；如果DBP≥90mmHg，试验组改为qid口服培哚普利4mg／吲哒帕胺1．25mg；对照组在纳催离SR的基础上加用美托洛尔50mg，qd，继续治疗6周。部分患者在治疗前及治疗12周时行动态血压检测（ABPM）。结果：用药后第6周时，试验组药物剂量加倍比率为48．6％（52／107），对照组有54．2％（52／96）的病例需加用美托洛尔，两组加药率比较无差异（P=0．43）。与给药前比较，治疗12周后两组DBP均明显下降（P〈0．01），下降幅度试验组和对照组平均为12．4和13．6mmHg（P=0．191），两组收缩压（SBP）在用药后各时点亦均明显下降（P〈0．01），下降幅度为15．4和15．7mmHg。两组ABPM各指标均明显下降，试验组和对照组的DBP各峰比（T／P）为80％和47％。两组不良事件发生率无差异，主要的不良事件为咳嗽、鼻炎、低钾血症。结论：2种治疗方法12周后均可显著降低DBP和SBP。试验组可以维持24h平稳降压。两组不良反应发生率相似。     

吉非替尼治疗老年晚期非小细胞肺癌的疗效观察

目的：探讨吉非替尼治疗老年晚期非小细胞肺癌的有效性和安全性。方法：对照组34例采用放疗进行治疗,观察组37例给予口服吉非替尼250mg／次,1次／日,比较两组的治疗总有效率、疾病控制率、不良反应发生率及治疗前后的血清糖蛋白型肺癌标志物（CA125）、粘蛋白型糖抗原（CA242）及癌胚抗原（CEA）水平的变化。结果：观察组治疗总有效率和疾病控制率均高于对照组（χ2=3．903,χ2=4．214,P〈0．05）;治疗后两组患者血清CA125、CA242及CEA水平均明显下降（P〈0．05,P〈0．01）,观察组CA125和CEA低于对照组（P〈0．05）;观察组不良反应发生率低于对照组,但两组差异无统计学意义（P〉0．05）。结论：吉非替尼治疗老年中晚期非小细胞肺癌患者的临床疗效确切,耐受性好,不良反应少,值得广泛推广。     

替米沙坦对终末期肾功能衰竭患者血液透析过程中高血压控制的研究

目的探讨替米沙坦对终末期肾功能衰竭患者血液透析过程中高血压的控制。方法选择在血液透析过程中伴有高血压症状的终末期肾功能衰竭患者62例，随机分为观察组和对照组各31例，观察组患者服用硝苯地平10mg．3次／d、美托洛尔50mg，3次／d、替米沙坦10mg，1次／d。对照组患者服用硝苯地平10mg，3次／d、美托洛尔50mg，3次／d、依那普利10mg，2次／d。观测两组病例治疗前及治疗12周后早晨6时血压、动态血压以及超声心动图变化。结果两组治疗12周后早晨6时血压、舒张晚期最大血流速度和舒张早期最大血流速度比值（A／E值）较治疗前均有显著下降（tSBP=2．5554，tDBP=3．7254，均P〈0．01；t1=2．8353，t2=5．1243，均P〈0．05）；动态血压检测结果提示观察组对夜间收缩压和舒张压均有显著下降（tSBP1=4．1696，tDBP1=3．8113，均P〈0．05），并优于对照组（tSBP2=2．6062，tDBP2=3．2179，P〈0．05），且不影响血压昼夜节律及心率，无明显不良反应发生。结论替米沙坦是治疗终末期肾功能衰竭患者血液透析过程中高血压的有效药物。     

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.     

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.