微生物法测定血浆中头孢泊肟浓度的方法研究

目的建立一种检测血浆中头孢泊肟的微生物检测方法.方法克雷伯肺炎杆菌、藤黄八叠微球菌作菌株在不同培养基及不同菌量检测血浆中头孢泊肟浓度.结果用克雷伯肺炎杆菌0.05ml作检验定菌,在低(0.16mg/l)、中(1.25mg/l)、高(5mg/l)三个浓度的回收率范围为84.5%～102.9%.日内、日间差异在5.3%～7.0%范围之内,室温、冻融、长期稳定性均在要求范围.标准曲线范围为0.04～10mg/l,相关系数r=0.9993,方法稳定可靠.结论此方法可用于头孢泊肟酯类药物的药动学和生物利用度研究.     

微生物法测定血浆中头孢泊肟浓度的方法研究

目的 建立一种检测血浆中头孢泊肟的微生物检测方法。方法 克雷伯肺炎杆菌、藤黄八叠微球菌作菌株在不同培养基及不同菌量检测血浆中头孢泊肟浓度。结果 用克雷伯肺炎杆菌0．05ml作检验定菌，在低（0．16mg/l)、中（1．25mg／l）、高（5mg/l）三个浓度的回收率范围为84．5％－102．9％。日内、日间差异在5．3％－7．0％范围之内，室温、冻融、长期稳定性均在要求范围。标准曲线范围为0．04－10mg/l，相关系数r＝0．9993，方法稳定可靠。结论 此方法可用于头孢泊肟酯类药物的药动学和生物利用度研究。     

头孢吡肟对肺炎克雷伯氏菌和大肠埃希氏菌的体外敏感性

目的　评价第四代头孢菌素头孢吡肟对 4 2 6株肺炎克雷伯氏菌和大肠埃希氏菌的体外敏感性。方法　收集 2 0 0 1年 3～ 10月福州地区 4家医院分离的肺炎克雷伯氏菌和大肠埃希氏菌 4 2 6株 ,用 Kirby-Bauer琼脂扩散法作药敏试验 :用表型确认试验检测 ESBL s。结果　 4 2 6株肺炎克雷伯氏菌和大肠埃希氏菌中 ,头孢吡肟的敏感性为 94 .37% ,仅次于亚胺培南 (10 0 % )、头孢哌酮 /舒巴坦 (10 0 % )和哌拉西林 /三唑巴坦(99.5 3% ) ,明显高于青霉素类抗生素哌拉西林 (48.83% )和第二代头孢菌素头孢呋辛 (6 0 .0 9% ) ,也高于第三代头孢菌素头孢曲松 (6 2 .91% )、头孢噻肟 (6 4 .79% )、头孢哌酮 (6 5 .73% )和头孢他啶 (88.2 6 % )。经表型确认试验证实 14 2株 (33.33% )为产超广谱 β-内酰胺酶 (ESBL s)菌 ;头孢吡肟对产 ESBL s菌和非产 ESBL s菌体外敏感性分别为 84 .5 1%、99.30 %。结论　头孢吡肟对肺炎克雷伯氏菌和大肠埃希氏菌的体外抗菌活性高于第三代头孢菌素 ,低于亚胺培南、头孢哌酮 /舒巴坦和哌拉西林 /三唑巴坦 ,头孢吡肟可考虑作为医院内感染的经验性一线用药。     

固相萃取高效液相色谱法测定人血浆中头孢泊肟浓度

目的 :建立人血浆中头孢泊肟的高效液相色谱测定法。方法 :采用固相萃取法预处理血浆样品 ,分析柱为M N Necleosil 10 0 5C18柱 (15 0mm× 4 .6mm ,5 μm) ,流动相为pH 3.8的 0 .0 5mol·L-1醋酸缓冲液 甲醇 (82∶18) ,流速为 1mL·min-1,检测波长为 2 34nm ,柱温为 39℃ ,按内标法定量。结果 :头孢泊肟与内标固定物的保留时间为 7.77min和 8.93min ;头孢泊肟血药浓度线性范围为 0 .0 5～ 5 .0mg·L-1(r =0 .9999) ,最低检测浓度为 0 .0 2 5mg·L-1(S/N≥ 3) ,萃取回收率在 84 %～ 95 % (n =5 ) ,分析方法回收率在 98%～ 10 6 % (n =5 ) ,日内和日间RSD分别为 2 .5 %～ 6 .6 %和 1.8%～ 4 .2 % (n =5 )。结论 :本法操作便捷 ,灵敏度和精密度高 ,重现性好 ,适于头孢泊肟的药动学研究     

反相高效液相色谱法测定头孢泊肟酯干混悬剂中头孢泊肟酯的含量

目的　建立测定头孢泊肟酯干混悬剂中头孢泊肟酯含量的方法。方法　采用反相高效液相色谱法 ,色谱柱为Shim Pack苯基柱 ( 4 μm ,3.9mm× 15 0mm) ;流动相 :0 .0 0 5mol/L磷酸二氢钾 ( pH6 .5 ) 乙腈 甲醇 ( 6 0∶10∶30 ) ;检测波长为 2 6 0nm。结果　精密度及稳定性均良好 ;头孢泊肟酯 (按头孢泊肟计 )在 5 0～ 2 5 0 μg/mL内 ,峰面积与浓度呈良好的线性关系 ,相关系数为 0 .9999,平均回收率为 99.91% ,RSD =0 .4 2 %。结论　本方法简便、准确、灵敏可靠     

HPLC法测定人血浆中头孢泊肟的浓度

目的建立测定人血浆中头孢泊肟酯的活性代谢产物头孢泊肟浓度的高效液相色谱法,并应用于头孢泊肟酯干混悬剂在健康人体内的药动学研究。方法采用沉淀蛋白法进行样品预处理,色谱柱为Agilent Zorbax SB-C18柱(150 mm×4.6 mm,5μm),流动相为乙腈-20 mmol.L-1磷酸二氢铵缓冲液(体积比为9∶91,含6.6 mmol.L-1三乙胺,磷酸调pH值至2.0),流速为1.0 mL.min-1,检测波长为254 nm,内标为头孢克洛。结果头孢泊肟浓度线性范围为0.102～6.528 mg.L-1,低、中、高3个质量浓度的提取回收率分别为92.0%、93.3%和92.1%,日内和日间精密度RSD(n=6)分别为3.3%、3.8%、2.0%和14.2%、2.9%、6.3%。头孢泊肟血浆样品室温放置2 h、预处理后室温放置24 h、经历1次及3次冷冻-解冻循环和-20℃冷冻情况下保存40 d均可保持稳定。结论此法适用于头孢泊肟酯药动学研究。     

SPE-HPLC法测定人血浆中头孢吡肟的浓度

目的:建立测定人血浆中头孢吡肟浓度的方法.方法:采用固相萃取(SPE)血浆中头孢吡肟.色谱柱为大连依利特Hypersil BDS C18,流动相为甲醇-磷酸盐缓冲液(20:80),柱温为30℃,流速为1 ml·min-1,检测波长为257 nm,进样量20 μl.结果:头孢吡肟检测浓度线性范围为1.0～200 mg·L-1(r＝0.999 9);最低检测限为1 mg·L-1;低、中、高3种浓度头孢吡肟的方法回收率分别为118.0%,97.0%,95.0%,日内RSD分别为1.7%,3.6%,2.1%,日间RSD分别为8.2%,4.9%,2.6%.结论:该方法简便、灵敏度高,适用于测定人血浆中头孢吡肟的含量.     

头孢泊肟匹酯片溶出度测定方法

本文建立了头孢泊肟匹酯片溶出度测定方法。以盐酸溶液 (9→ 10 0 0 )为溶剂 ,转速 10 0 r/ min,采用紫外分光光度法测定头孢泊肟匹酯片溶出量 ,测定波长为 2 6 3nm。线性浓度范围 3～ 2 4μg/ ml,r=0 .9999。经 30 min取样 ,三批头孢泊肟匹酯片的溶出量均大于 90 %。方法简便、准确 ,重复性好     

头孢泊肟酯干混悬剂人体生物等效性研究

目的 在健康受试者中观察头孢泊肟酯干混悬剂的药动学特性及其与片剂的生物等效性.方法 按标签开放性随机自身交叉设计,20例健康男性受试者分别口服单剂量头孢泊肟酯干混悬剂和片剂,头孢泊肟酯剂量均为100 mg,血浆头孢泊肟的浓度采用高效液相色谱法(HPLC)检测.结果 头孢泊肟酯干混悬剂和片剂对应tmax分别为(2.55±0.67)和(2.75±0.66)h,Cmax分别为(1.958±0.380)和(1.847±0.506)μg/mL,AUC0→t分别为(10.68+2.18)和(10.06±2.63)h·μg/mL.头孢泊肟酯干混悬剂相对于片剂的平均相对生物利用度为(109.18±18.44)%.两种制剂的AUC0→t和Cmax均无显著差异(P>0.05).结论 头孢泊肟酯干混悬剂与头孢泊肟酯片剂具有生物等效性,结果 可供临床参考.     

头孢卡品酯对细菌感染小鼠败血症的体内抗菌作用研究报告

目的 评价头孢卡品酯对我国近三年临床分离致病菌所致小鼠败血症的体内抗菌作用.方法 以0.5mL最小致死量(MLD)腹腔注射细菌感染小鼠,建立小鼠败血症实验模型,灌胃0.5mL不同剂量的抗菌药物,记录给药后1～7d内小鼠成活率,用BLISS法计算50％、95％有效剂量(ED50、ED95)及P值.结果 对4株临床分离致病菌进行了体内保护试验.结果显示,头孢卡品酯对不产ESBLs的大肠埃希菌、肺炎克雷伯菌以及甲氧西林敏感金葡菌、青霉素敏感肺炎链球菌的ED50值在0.381～3.613mg/kg,ED95值在1.304-17.939mg/kg.结论 头孢卡品酯对所测革兰阴性菌的体内抗菌作用优于革兰阳性菌.对体外抗菌活性优于头孢泊肟的菌株,体内抗菌作用也基本优于头孢泊肟酯.     

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.

---

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.

     

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.     

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.     

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.     

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.