布洛芬对大鼠体温降低作用的昼夜节律研究

目的:研究布洛芬不同时辰给药对大鼠体温降低作用及血药浓度的昼夜节律变化规律。方法:采用随机区组实验设计,60只大鼠分别在不同时间(2:00、6:00、10:00、14:00、18:00、22:00)单次灌胃给予布洛芬颗粒50mg.kg-1,另取10只为空白对照,观察大鼠体温和血药浓度的昼夜节律变化规律,以时间图和余弦法进行分析。结果:大鼠正常体温及用药后体温均呈现明显的昼夜节律变化,峰值相位及振幅无显著改变,仅均值下降;最佳拟合曲线分别为Yti=38.7+0.52Cos(15°×ti—86.80°)和Yti=37.8+0.55Cos(15°×ti—117°)。大鼠在不同时辰给药血药浓度亦呈现明显的昼夜节律变化,明期血药浓度高于暗期,最佳拟合曲线Yti=41.95+5.30Cos(15°×ti—272.83°)。结论:大鼠在不同时辰给予布洛芬,体温和血药浓度均存在昼夜节律的差异。     

阿斯匹林对小鼠正常体温的降低作用及其昼夜节律变化

一般认为水杨酸类药物仅降低处于高热状态的体温而不影响正常体温。但本文实验表明，大剂量阿斯匹林（ＡＳＰ）（２００ｍｇ·ｋｇ－１，ｉｐ）使雄性ＩＣＲ小鼠的正常体温明显下降，且该作用呈昼夜节律性变化。ＡＳＰ用药后血浆水杨酸浓度也呈昼夜变化，但与药物的体温降低作用无明显的正相关关系。提示ＡＳＰ用药后的体温降低作用的昼夜节律主要与动物体温的昼夜节律相关。     

布洛芬二元醇脂质体温敏凝胶的处方筛选与体外释放研究

目的:制备布洛芬二元醇脂质体温敏凝胶,研究其体外释放特性。方法:以泊洛沙姆407(P407)和泊洛沙姆188(P188)为凝胶基质,采用冷溶法制备布洛芬二元醇脂质体温敏凝胶;以胶凝温度为指标,以P407、P188比例(g/100 ml)与布洛芬二元醇脂质体的加入量为因素,采用正交试验对布洛芬二元醇脂质体温敏凝胶处方进行优化;采用Franz扩散池法比较布洛芬乙醇溶液、布洛芬二元醇脂质体、布洛芬P407二元醇脂质体温敏凝胶和优选制备的布洛芬P407/P188二元醇脂质体温敏凝胶的体外释放特性。结果:最优处方为32%P407、3.2%P188及2.5 ml的布洛芬二元醇脂质体,所制温敏凝胶的胶凝温度为(32.1±0.5);体外释放结果显示,与布洛芬乙醇溶液及布洛芬二元醇脂质体比较,优选制备的温敏凝胶具有明显缓释作用,其12 h内累积释放度为(40.9±0.43)%,24 h内累积释放度为(60.76±0.58)%,符合一级释药模型;布洛芬P407二元醇脂质体温敏凝胶和优选制备的温敏凝胶的体外释放特性无明显差异。结论:成功制得具有温敏特性和明显缓释作用的布洛芬二元醇脂质体温敏凝胶。     

阿斯匹林对小鼠正常体温的降低作用及其昼夜节律变化

一般认为水杨酸类药物仅降低处于高热状态的体温而不影响正常体温。但本文实验表明,大剂量阿斯匹林(ASP)(200mg·kg^-1,ip)使雄性ICR小鼠的正常体温明显下降,且该作用呈昼夜节律性变化。ASP用药后血浆水杨酸浓度也呈昼夜变化,但与药物的体温降低作用无明显的正相关关系。提示ASP用药后的体温降低作用的昼夜节律主要与动物体温的昼夜节律相关。     

中西医结合治疗小儿热性惊厥疗效观察

目的研究清热止惊汤联合布洛芬混合液治疗小儿热性惊厥的疗效。方法选择63例呼吸道感染引起的热性惊厥患儿作为研究对象,随机分为给予清热止惊汤联合布洛芬混合液治疗32例的治疗组和清热止惊汤治疗31例的对照组,观察惊厥治疗效果、体温情况以及呼吸道症状缓解时间。结果治疗组总有效率明显高于对照组（P〈0.05）;咳嗽、咳痰、气喘、肺部啰音缓解时间均明显短于对照组（P〈0.05）;治疗组患儿从治疗后15 min开始体温明显低于治疗前,对照组患儿从治疗后45 min体温明显低于治疗前。结论清热止惊汤联合布洛芬混合液治疗小儿热性惊厥,能够更为快速地降低体温,改善呼吸道症状,更为有效地控制惊厥状态,是治疗小儿热性惊厥行之有效的方法。     

布洛芬对小儿急性呼吸道感染的退热作用观察

目的观察布洛芬混悬液的退热效果。方法选择有高热症状的急性上呼吸道感染患儿100例，随机分为两组，分别用布洛芬混悬液（56例）和对乙酰氨基酚口服溶液（44例）治疗，记录首次给药后0．5、1．0、1．5、2．0、3．0、4．0、5．0和6．0h的体温变化。结果布洛芬组和对乙酰氨基酚组体温降低1．5℃所需的平均时间分别为（1104-78）min、（1194-82）min，比例分别为83．9％和84．1％（P〉0．05）。前2h两组体温下降相似，在3．0、4．0、5．0和6．0h布洛芬组平均体温下降大于对乙酰氨基酚组，体温正常化维持时间更长。结论布洛芬退热疗效优于对乙酰氨基酚。     

布洛芬混悬液与安痛定注射液临床疗效的对照观察

目的：观察比较布洛芬混悬液与安痛定注射液的退热疗效。方法：选择有高热症状的急性上呼吸道感染患儿(腋温≥39．1℃)76例随机分成两组，分别用布洛芬混悬液和安痛定注射液治疗。结果：在第1小时内两药退热效果和速度相同，而布洛芬混悬液在第2小时就能使患儿体温降至接近正常体温，并能维持6～8小时；安痛定注射液未能将体温退至正常，用药后4小时体温有回升趋势。布洛芬混悬液对咽痛、头痛的缓解也比安痛定更为显著。结论：布洛芬混悬液退热作用强，维持时间长，对咽痛、头痛的缓解疗效较安痛定显著。     

布洛芬水溶性凝胶的制备工艺研究

目的:研究布洛芬水溶性凝胶的最佳制备工艺.方法:以正交试验方法筛选基质最佳处方.结果:最佳基质处方为泊洛沙姆p407/p188(15%:20%)、海藻酸钠0.6%、乙醇15%,由此制得的布洛芬水溶性凝胶在体温下胶凝,粘度适中.结论:该处方设计合理.制备工艺稳定.     

布洛芬混悬液与对乙酰氨基酚在小儿高热治疗中的临床疗效观察

目的：观察布洛芬混悬液与对乙酰氨基酚在小儿高热治疗中的临床疗效。方法：本文选取我院2013年8月～2014年8月收治的100例高热患儿，随机分为治疗组和对照组，对照组采用对乙酰氨基酚实施治疗，治疗组采用布洛芬混悬液实施治疗，对比两组临床疗效、治疗前后体温变化情况以及不良反应发生率。结果：治疗后治疗组体温测定为（36.92±0.61）℃，对照组体温测定为（38.03±0.49）℃，两组对比存在显著差异（P<0.05），具有统计学意义。结论：小儿高热采用布洛芬混悬液开展治疗，临床疗效更加显著，对于调整和控制体温有着重要作用，值得临床推广。     

右旋布洛芬与布洛芬混悬液退热疗效的对照研究

目的比较右旋布洛芬与布洛芬混悬液治疗儿童感染性高热的临床疗效。方法将有高热症状的急性上呼吸道感染患儿238例随机分为2组,分别给予口服右旋布洛芬和布洛芬混悬液退热,采用腋温法检测用药前和用药不同时间后的体温,并计算体温下降的幅度。结果右旋布洛芬和布洛芬混悬液都具有很好的依从性,但右旋布洛芬退热速度更快,作用更强,维持退热时间更长。结论右旋布洛芬混悬液退热疗效优于布洛芬混悬液。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.