反相高效液相色谱法测定人血浆中氨溴索浓度

目的：建立测定血浆中氨溴索浓度的反相高效液相色谱法。方法：血浆样品用乙醚提取,醚层经００１ｍｏｌ·Ｌ－１盐酸提取后进样,色谱柱为ＲｅｓｏｌｖｅＣ１８４６ｍｍ×２５０ｍｍ（５μｍ）,流动相为乙腈－甲醇－００１ｍｏｌ·Ｌ－１ｐＨ７０磷酸盐缓冲液－四氢呋喃（３５０∶３５０∶２７５∶２５）,流速１５ｍＬ·ｍｉｎ－１,检测波长２４２ｎｍ,外标法峰高定量。结果：本法最低检测浓度５ｎｇ·ｍＬ－１,线性范围１０～３２０ｎｇ·ｍＬ－１,回归方程为Ｈ＝２４５＋１６４Ｃ,ｒ＝０９９９５,日内ＲＳＤ为２７％～５３％,日间ＲＳＤ为３２％～８２％。结论：该法适用于盐酸氨溴索片的药代动力学研究。     

高效液相色谱法测定盐酸氨基胍片中盐酸氨基膈的含量

目的：用高效液相色谱法(HPLC法)测定盐酸氨基胍片含量。方法：采用C18柱，以乙腈—0．025mol／LKH2PO4(含0．596三乙胺，pH＝3．5)(30：70)为流动相，检测波长为213nm。结果：盐酸免基瓜浓度在82～810μg/mL范围内与峰面积有良好的线性关系，r＝0．9998；平均回收率为100．0％，RSD＝0．96％，n＝9；日内差＝0．25％，日间差RSD＝0．11％。结论：HPLC法可以用于盐酸氨基胍片的含量测定。     

盐酸普罗帕酮片及注射液的HPLC测定

建立了测定盐酸普罗帕酮片及注射液含量与有关物质的HPLC法,采用Shim-pack CLC ODS色谱柱,流动相为乙腈－0．01mol/L磷酸氢二铵溶液（2：1,用磷酸调节pH值至4．6）,检测波长为246nm,线性范围为30－270ug/ml,相关系数为0．9999,片剂和注射液的平均回收率分别为101．4％（RSD＝1．4％）和101．3％（RSD＝0．96％）,盐酸普罗帕酮,环氧酚和AK－26的最低检出量分别为0．3,0．17和0．39ng。     

高效液相色谱法测定头孢泊肟酯及其制剂的含量

建立一种用高效液相色谱法测定头孢泊肟酯及其片剂，胶囊剂的含量及有关物质的方法。方法：以ODS为固定相。甲醇－水（41：59）为流动相；检测波长为240nm。结果：头孢泊肟酯的浓度在0.3-0.9mg/ml范围内线性关系良好，回归方程为：Y＝1460374，8X-4983．9，r=0.9999。头孢泊肟酯，头孢泊肟酯片和头孢泊肟酯胶囊重现性良好（n=9)，RSD分别为0．5％，1．0％和1．2％。头孢泊肟酯片和头孢泊肟酯胶囊平均回收率分别为100．6％（RSD＝1．0％，n=9)和99．8％（RSD＝0．8％，n=90。本方法简单，快速，结果准确。     

人血浆中美洛昔康的高效液相色谱测定法

目的：建立人血浆中美洛昔康的高效液相色谱测定方法。方法：用外标法,以四氢呋喃提取血浆中的美洛昔康,用高效液相色谱法测定美洛昔康。色谱柱：瑞典KRomasil,ODS C18.流动相：水－甲醇－乙腈－冰醋酸（500：600：50：20）,内含1．01g庚烷磺酸钠,流速1mL.min^-1,检测波长：355nm。结果：本测定方法的提取回收率为97．7％－101．9％,RSD为1．91％－5．79％,人血浆中美洛昔康的最低检测度为0．122ug.mL^-1,线性范围为：0．122－7．83ug.mL^-1。结论：本法操作简单,准确,灵敏度高,可用于美洛昔康胶囊和片剂的药代动力学和生物利用度的测定。     

反相高效液相色谱法测定人血清中曲昔派特浓度

目的：建立测定人血清中曲昔派特浓度的反相高效液相色谱法。方法：血浆样品用乙酸乙酯萃取后进样。选用美国Beckman 344型高效液相色 谱仪。Ultrasphere ODS(250mm*4.6mm,5um)色谱柱。流动相为甲醇－0．01mol.L^-1 pH2.5的磷酸二氢钠缓冲液（35：65）,流速1mL.min^-1,茶碱作内标,紫外检测波长254mm,内标法峰高定量。结果：本法高,中低浓度的萃取回收率为79．4％－81．1％,方法回收率为97．3％－105．0％,日内RSD＜5％,日间RSD＜10％。结论：本法快捷,灵敏,准确,适用于曲昔派特血药浓度测定及药代动力学研究。     

反相高效液相色谱法测定盐酸乙哌立松片剂的含量

目的：建立高效液相色谱法测定盐酸乙哌立公片含量的方法。方法：酸盐乙哌立松片加甲醇,超声振荡,过滤后以ODS C18为分析柱,以甲醇－水－三乙胺（80：19．5：0．5,V／V）为流动相,托哌酮为内标,于254nm波长检测。结果：盐酸乙哌立松在0．4－1．6mg/ml浓度范围内线性关系良好（r=0.9999),平均回收率98．4％,RSD,1．2％,三批协酸乙哌立松片含量测定结果分别为标示量的97．8％,98．3％和98．9％,结论：方法快速,准确,专一性强,适用于盐酸乙哌立松片的含量测定。     

阿斯咪唑片剂人体药代动力学和生物利用度的初步研究

目的：观察阿斯咪唑片剂的人体药代动力学和生物利用率。方法：用放射免疫法测定血浆阿斯咪唑＋去甲阿斯咪唑含量，按交叉设计法对国产和进口阿斯咪唑片进行健康中国人体的药物代谢学比较研究，并求得相对生物利用率。用3P87软件处理，结果与结论：阿斯咪唑的药代动力学呈二室模型。主要药代动力学参数：国产片：Vd=5.34±1．85L;αT1／2＝0．74±0．37h;βT1／2＝286．10±220．11h；CL＝0．052±0．031ng/ml;Tmax=1.56±1．32h;Cmax=1.04±0．10ng/ml;AUC=262.69±162．18ng/ml·h^-1。进口片：Vd=8.24±2．56L；αT1／2＝1．16±0．98h;βT1／2＝260．38±260．37h；CL＝0．089±0．079ng/ml;Tmax=1.37±0．82h;Cmax=0.93±0．14ng/ml;AUC=250.66±148．05ng/ml·h^-1。国产片对进口片的相对生物利用率为127．8％。     

紫外分光光度法测定尿中氧氟沙星的排泄量

目的：对国产氧氟沙星片药代动力学进行研究。方法：采用紫外分光光度法测定氧氟沙星尿药浓度。结果：药代动力学参数分别为：Ｋ＝０.１２７８ｈ;Ｔ１２＝５．９６ｈ;Ｘｕ０－２４＝１６５．８４ｍｇ;排泄率（Ｑ）＝８２８４％。结论：本法简便、快捷,可作为药代动力学研究和临床监测的有效方法。     

血浆中硝酸异小梨醇酯浓度测定及其药代动力学的研究

本文用气液色谱电子捕获检测法测定人血浆中硝酸异山梨醇酯的浓度。以乙醚-环已烷混合液作提取试剂，2，4－二硝基氯苯作内标，线性范围为8．5～169nmol／L，相关系数γ＝0．994；最低检测量为4．2nmol／L；平均回收率为91．98±6．8％；日内误差（CV％）和田间误差（CV％）分别为2．9％和7．3％。应用本法测定了正常人口服和经皮肤贴敷给药后硝酸异山梨醇酯的血药浓度，并进行药代动力学的研究，参数计算结果属一房室模型，半衰期为8．0min。     

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.     

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.     

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.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.