反相高效液相色谱法测定5-氨基水杨酸及其代谢物在人血浆及尿中的浓度

目的：研究５－氨基水杨酸及其代谢物在人血浆及尿中的浓度。方法：反相高效液相色谱法（ＲＰ－ＨＰＬＣ）为测定方法。结果：血浆测定两者线性范围均为０．０８～８．００μｇ·ｍｌ－１，最低检出浓度均为０．０４μｇ·ｍｌ－１，两者平均回收率分别为８７．９３％，９１．４８％，日内ＲＳＤ分别为６．０４％，５．５１％，日间ＲＳＤ分别为７．９８％，４．４３％。５－氨基水杨酸尿浓度测定线性范围为０．５～１０μｇ·ｍｌ－１，最低检出浓度为０．２５μｇ·ｍｌ－１，平均回收率为１０１．８３％，日内ＲＳＤ为１．５７％，日间ＲＳＤ为２．６４％。结论：该测定方法快速，简便，灵敏     

尼莫地平控释片释放度试验研究

本文研究了尼莫地平控释片的释放度试验方法——转篮法，释放介质为含有２２％异丙醇的０．１ｍｏｌ·Ｌ－１盐酸液；磷酸盐缓冲液（ｐＨ５．８）和ｐＨ７．２的溶液。含量测定方法：紫外分光光度法，在三种介质中尼莫地平分别在１～３０μｇ·ｍｌ－１，１０～５０μｇ·ｍｌ－１和１０～５０μｇ·ｍｌ－１的范围内，浓度与吸收度有较好的线性关系。回归方程分别为Ａ＝０．６１５Ｃ＋０．０２３（ｒ＝０．９９９９）；Ａ＝０．０６１４Ｃ＋０．０１２（ｒ＝０．９９９５）；Ａ＝０．０６１２Ｃ＋０．００８８（ｒ＝０．９９９９）。平均回收率分别为９９．６３％，９９．９８％及１００．７７％，ＲＳＤ（％）分别为１．３４％，１．５９％及１．４１％。本方法的体外释放百分率与体内吸收分数有较好的相关性（ｒ＝０．９９１）。     

阿莫西林克拉维酸钾口服干混悬剂含量测定方法研究

目的：对阿莫西林克拉维酸钾口服干混悬剂含量测定方法研究。方法：采用高效液相色谱法，在３×３ＣＲＣ１８柱（４ｍｍ×３．５ｃｍ）上，以ｐＨ４．４磷酸二氢钠溶液－甲醇（９５∶５）为流动相，流速１．０ｍｌ·ｍｉｎ－１，检测波长为２２０ｎｍ。结果：阿莫西林和克拉维酸浓度分别在２５～５００μｇ·ｍｌ－１及１０～２００μｇ·ｍｌ－１范围内有良好的线性关系，平均方法回收率分别为９９．４％±１．９％和９９．５％±２．０％，日内精密度分别在１．１％～２．３％和１．７％～２．６％之间，日间精密度分别＜３．１％和＜２．５％。结论：本法实用简便，结果可靠。     

吲哚美辛缓释胶囊单剂量与多剂量达稳态时的相对生物利用度

采用反相高效液相色谱法测定１１名健康志愿受试者单剂量口服７５ｍｇ和多剂量口服吲哚美辛缓释胶囊和吲哚美辛片后，吲哚美辛血药浓度变化情况。测得单剂量口服７５ｍｇ吲哚美辛缓释胶囊与吲哚美辛片的达峰时间分别是４．０ｈ与１．５ｈ，峰浓度分别是１．０２μｇ·ｍｌ－１与３．７μｇ·ｍｌ－１，吲哚美辛缓释胶囊的相对生物利用度为１０２％。测得多剂量口服吲哚美辛缓释胶囊与吲哚美辛片达稳态后的Ｃｍｉｎ分别是０．２０８μｇ·ｍｌ－１与０．２６３μｇ·ｍｌ－１，Ｃｍａｘ分别是１．２６μｇ·ｍｌ－１与１．２２６μｇ·ｍｌ－１，Ｔｍａｘ分别为２．７７ｈ与１．８２ｈ，ＦＩ分别是１４０．８１％与１２８．２１％。以ＡＵＣ为指标，经统计分析，吲哚美辛缓释胶囊与吲哚美辛片在单剂量和多剂量达稳态时是生物等效制剂。     

Effects of heparin on growth factor-induced mitogenic and proliferative responses of rat pulmonary a

目的：探讨肝素是否能抑制生长因子诱导的大鼠肺动脉平滑肌细胞（ＰＡＳＭＣ）分裂和增殖．方法：应用含１０％ＦＢＳ的Ｍ１９９培养液培养大鼠ＰＡＳＭＣ．细胞分裂及细胞增殖分别用［ｍｅｔｈｙｌ３Ｈ］ＴｄＲ和细胞计数监测．结果：ＦＢＳ（１０％），以及ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ－１），ＦＧＦ（５０μｇ·Ｌ－１），或ＩＬ１α（１００ｎｇ·Ｌ－１）联合应用均能增加大鼠ＰＡＳＭＣ分裂．肝素（１００ｍｇ·Ｌ－１）抑制１０％ＦＢＳ诱导的大鼠ＰＡＳＭＣ增殖（２８％±６％）和胸腺嘧啶摄取反应（２７％±７％），抑制ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ－１），ＦＧＦ（５０μｇ·Ｌ－１），或ＩＬ１α（１００ｎｇ·Ｌ－１）联用诱导的大鼠ＰＡＳＭＣ增殖（２５％±６％，２７％±７％，２０％±４％），以及胸腺嘧啶摄取反应（２３％±７％，２６％±６％，２０％±６％）．结论：肝素抑制生长因子诱导的大鼠ＰＡＳＭＣ的分裂与增殖．     

Use of cafeine as a probe for rapid determination of cytochrome P-450 CYP1A2 activity in humans

目的：建立快速测定细胞色素Ｐ４５０ＣＹＰ１Ａ２酶活性的高压液相色谱方法．方法：取３００μＬ血浆样品，用β羟乙基茶碱作内标，经５ｍＬ氯仿／异丙醇（９∶１）萃取处理后，用００５％的乙酸、乙腈和甲醇作为基本流动相，采用梯度洗脱程序在ＯＤＳ柱上分离待测组分，紫外检测波长２８２ｎｍ．结果：无内源性物质干扰测定．次黄嘌呤、内标和咖啡因快速基线分离，三者的保留时间均小于１３分钟．次黄嘌呤和咖啡因的检测下限均为０１μｍｏｌ·Ｌ－１，线性范围分别为１－１００μｍｏｌ·Ｌ－１和１－２００μｍｏｌ·Ｌ－１，相关系数分别为０９９９９和０９９８７，变异系数分别小于６％和１０％．两者的平均相对回收率为９６％－１０８％．结论：本方法快速、灵敏，可用于人群ＣＹＰ１Ａ２酶活性研究．     

Inhibitory effect of trapidil on proliferation of cultured rat aortic smooth muscle cells induced by endothelin-1

目的：观察曲匹地尔（Ｔｒａ）对内皮素１诱导的血管平滑肌细胞（ＶＳＭＣ）增生的影响．方法：测定ＶＳＭＣ数目，［３Ｈ］ＴｄＲ参入细胞ＤＮＡ的放射活性及ＶＳＭＣ的细胞周期分布．结果：内皮素１１００ｎｍｏｌ·Ｌ－１处理大鼠ＶＳＭＣ后，细胞数，［３Ｈ］ＴｄＲ摄取及细胞分裂增殖活性等分别增加１３４％±２３％，２１２％±７１％和８６％±１８％，Ｔｒａ５，５０，５００μｍｏｌ·Ｌ－１对上述参数的抑制率分别为１２％－４８％，３５％－５４％和１５％－４７％．Ｔｒａ５０μｍｏｌ·Ｌ－１和５００μｍｏｌ·Ｌ－１对未经内皮素处理的细胞的生长无明显作用．结论：Ｔｒａ对内皮素１诱导的培养大鼠ＶＳＭＣ的增生具有阻抑作用．     

Ge－132赖氨酸盐的抗癌作用

Ｇｅ－１３２赖氨酸盐２００ｍｇ·ｋｇ－１·ｄ－１×１０ｄ及１００ｍｇ·ｋｇ－１·ｄ－１×１０ｄｉｇ对小鼠移植性Ｓ１８０荷瘤实体瘤的抑制率分别为４６．７％、３４．７％，对小鼠移植性Ｈ２２肝癌实体瘤的抑制率分别为４２．５％、３５．２％。２００ｍｇ·ｋｇ－１·ｄ－１×１５·ｄ及１００ｍｇ·ｋｇ－１·ｄ－１×１５ｄｉｇ对小鼠移植性ＬＬＣ肺癌实体瘤的抑制率分别为８１．７％、６１．７％，其抑制率均高于Ｇｅ－１３２同剂量组。Ｇｅ－１３２赖氨酸盐对Ｈ２２肝癌腹水型小鼠的生命延长率明显大于ＮＳ组及Ｇｅ－１３２组。提示Ｇｅ－１３２赖氨酸盐的抗癌作用比Ｇｅ－１３２更明显。     

Inhibitory Effect of β-Elemene Emulsion on Platelet Aggregation and its Mechanism

为阐明β榄香烯的抗血小板作用，本文分别采用比浊法和放免法测定大鼠连续ｉｐ７ｄβ榄香烯乳６．２５～１２．５ｍｇ·ｋｇ－１·ｄ－１后对血小板聚集、血浆ｋｅｔｏＰＧＦ１α和ＴＸＢ２水平的影响。结果表明，本品分别使凝血酶、花生四烯酸和ＡＤＰ诱导血小板最大聚集率下降３８．３％～４２．６％，１４．７％～１９．１％和７．２％～１０．８％，血浆ＴＸＢ２从８８ｎｇ·Ｌ－１下降至７２ｎｇ·Ｌ－１，ｋｅｔｏＰＧＦ１α从１７．５ｎｇ·Ｌ－１增加至２０．９ｎｇ·Ｌ－１。提示ＴＸＢ２降低和ｋｅｔｏＰＧＦ１α值增加是其抑制血小板聚集的作用机制之一。     

高效液相色谱法测定盐酸环丙沙星血药浓度及其药动学研究

采用高效液相色谱法（ＨＰＬＣ）测定盐酸环丙沙星的血药浓度。色谱条件为：紫外检测波长λ２７７ｎｍ；分析柱为ＨＰ－ＲＰ－ＯＤＳＣ１８柱，Φ４．６×２２０ｍｍ；流动相：乙腈∶（溴化四丁基铵０．００８ｍｏｌ·Ｌ－１＋磷酸二氢钾水溶液０．０１１ｍｏｌ·Ｌ－１）＝１４∶８６，配好后磷酸调ｐＨ至２．７４±０．０２。本法血清最低检出浓度０．０１μｇ·ｍｌ－１。对１０名受试者口服５００ｍｇ两种盐酸环丙沙星片后进行药动学和生物利用度研究。药－时曲线经拟合为二室开放模型，其Ｔ１／２β分别为４．６８±０．５３ｈ与４．４０±０．４７ｈ，Ｔｍａｘ分别为１．２８±０．０７ｈ与１．３３±０．０７ｈ，Ｃｍａｘ分别为６．４４±０．６１（μｇ·ｍｌ－１）与５．８８±０．４０（μｇ·ｍｌ－１），ＡＵＣ分别为１９．８８±１．８３（μｇ·ｈ－１·ｍｌ－１）和１９．２４±１．０８（μｇ·ｈ－１·ｍｌ－１）。供试品片剂的相对生物利用度为１０３．３２±４．８１％（９９．５８±４．６３％，经含量校正），经统计分析两种制剂具有生物等效性。     

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.     

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.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

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.