反相高效液相色谱法测定血浆和脑脊液中甲氨蝶呤浓度

目的：建立测定血浆和脑脊液中甲氨蝶呤的反相高效液相色谱方法。方法：采用ＯＤＳ不锈钢柱,流动相：甲醇∶０．０２５ｍｏｌ·Ｌ－１磷酸盐缓冲液（２１∶７９,ｐＨ６．７０）,检测波长：３０６ｎｍ,样品经沉淀蛋白质后直接进样。结果：血浆和脑脊液样品回收率分别为９７．５％±４．１％和１００．８％±１．５％,日内和日间误差（ＲＳＤ）均＜７％,最低检测浓度４．７５×１０－８ｍｏｌ·Ｌ－１,血浆中在１．１０×１０－７～２．２×１０－６ｍｏｌ·Ｌ－１和２．２０×１０－６～１．７６×１０－４ｍｏｌ·Ｌ－１;脑脊液中在１．１０×１０－７～２．２０×１０－６ｍｏｌ·Ｌ－１和２．２０×１０－６～１．１０×１０－３ｍｏｌ·Ｌ－１浓度范围内有良好线性关系,ｒ＝０．９９９６～０．９９９９。结论：本法简便、准确、灵敏。     

碳糊电极吸附伏安法测定微量酚磺乙胺

在００５ｍｏｌ／Ｌ硫酸底液中，用碳糊电极吸附伏安法测定酚磺乙胺，阳极峰电位为０５５Ｖ（ｖｓ．ＳＣＥ），峰电位与酚磺乙胺的浓度在１０×１０－７～１０×１０－４ｍｏｌ／Ｌ范围内呈良好的线性关系。该法检测下限为５０×１０－８ｍｏｌ／Ｌ，回收范围为９５０％～１０５５％，相对标准偏差为３０％（ｎ＝１２）。对酚磺乙胺注射液用本法进行了测定，获得满意结果。本文对反应机理进行了初步探讨，酚磺乙胺在碳糊电极上是一个两电子、两质子的不可逆过程     

胆骨化醇及其制剂的二阶导数差示脉冲极谱法定量研究

本文建立了胆骨化醇及其制剂的二阶导数差示脉冲极谱法定量测定方法。在２．０×ｌ０－５ｍｏｌ／ＬＫＣｌ底液中，于－１．６９Ｖ（ｖｓＡｇ／ＡｇＣｌ）处出现一良好的二阶导数差示脉冲极谱峰，在２．０×１０－５～１．２×１０－４ｍｏｌ／Ｌ范围内，胆骨化醇的浓度与其导数峰幅值呈非常显著的线性关系（ｐ＜０．０１），检测限为８．４×１０－９ｍｏｌ／Ｌ。方法简便、快速、灵敏，结果准确。     

4－（取代氨基酸酰胺基）－4－脱氧－4′－去甲基表鬼臼毒素的合成及其抗肿瘤活性

合成了１８个Ｎ－苄氧羰基保护的４－取代氨基酸酰胺基－４－脱氧－４′－去甲基表鬼臼毒素衍生物。它们在体外试验中显示出良好的抗Ｌ１２１０白血病细胞（ＩＣ５０２．７×１０－１～４．０×１０－４ｍｇ／Ｌ）和ＫＢ细胞的活性，部分新化合物的抗Ｌ１２１０和ＫＢ细胞的活性超过依托泊甙［Ｅｔｏｐｏｓｉｄｅ，ＩＣ５０（Ｌ１２１０）１．０×１０－１ｍｇ／Ｌ］。     

RP—HPLC法测定片剂中盐酸莫索尼定的含量

采用反相高效液相色谱法，选择苯酚为内标物，ＺＹ１１０４型ＸＷＧ－Ｃ１８柱（４．６ｍｍ×２５０ｍｍ）为分析柱，甲醇－水－０．２ｍｏｌ／Ｌ硫酸铵（１０．６８０．７２，ｐＨ＝７．７）为流动相，流速为１．０ｍＬ／ｍｉｎ，检测波长为２５４ｎｍ，进样量２０μＬ，测定片剂中盐酸莫索尼定的含量，按盐酸莫索尼定计算，理论板数为２５４４，样品峰与内标峰的分离度为３．９．线性范围为４～１００ｍｇ／Ｌ（ｒ＝０．９９９８），最低检测量为１０ｎｇ，平均回收率为９９．８２％，ＲＳＤ＝０．７９％．用该法测定３批盐酸莫索尼定片剂的含量，结果分别为（９６．８±１．９）％、（９９．４±１．７）％和（９９．３±１．６）％．本法快速、灵敏、准确，专属性高．     

氯霉素滴眼液的吸附伏安法测定

在０．０１ｍｏｌ／ＬＮａＯＨ溶液中，氯霉素具有灵敏的吸附还原波，峰电位在－０．５３Ｖ（ｖｓ．ＳＣＥ）。浓度在５．０×１０－３～２．５×１０－１μｇ／ｍｌ范围内，峰电流与浓度呈线性关系。可用吸附伏安法测定滴眼液中氯霉素含量，结果满意。     

微生物产生的淀粉酶抑制剂研究Ⅲ淀粉酶抑制剂抑制动力学研究

Ｓ－２－３５淀粉酶抑制剂是一种易溶于水、不溶于有机溶剂的白色粉末，其紫外谱图呈末端吸收，红外谱图在３３９１、１５７２、１４１０、１０３０及９２７ｃｍ￣（－１）处有明显吸收峰。该抑制剂在ｐＨ６．５的条件下对ａ－淀粉酶有明显的抑制作用（ＩＤ＿（５０）为１．７×１０－５ｍｏｌ／Ｌ）．在３７℃，ｐＨ６．５的磷酸缓冲液中，Ｓ－２－３５抑制剂对淀粉酶的抑制作用与抑制剂的浓度关系密切，在抑制剂浓度较小的情况下，抑制剂与酶的结合呈直线关系，随着抑制剂浓度增大，残留活力曲线则出现漂移。根据Ｄｉｘｏｎ图和Ｌｉｎｅｗｅａｖｅｒ－Ｂｕｒｋ图的研究表明，Ｓ－２－３５淀粉酶抑制剂对淀粉酶的结合和底物呈竞争性抑制，抑制常数Ｋ＿ｉ为１．５～１．６×１０￣（－６）ｍｏｌ／Ｌ。     

诺氟沙星治疗阿米巴肝脓肿

目的：探索新的、有效的治疗阿米巴肝脓肿的药物。方法：诺氟沙星０．３－０．４９，ｔｉｄ，ｐｏ×１５ｄ，治疗３０例（男性２２例，女性８例；年龄４５±ｓ３ａ）阿米巴肝脓肿病人。用０．５％甲硝唑１００ｍＬ静脉滴注（静滴），ｂｉｄ×（３－５）ｄ，以后改为０．４ｇ，ｔｉｄ，ｐｏ×（７－１０）ｄ治疗２９例作对照。２组合并细菌感染者均加用四环素１．０ｇ，ｑｄ，静滴５－７ｄ或用氨苄西林２．０ｇ，ｔｉｄ，ｉｖ×（５－７）ｄ。结果：诺氟沙星组在治疗有效率，体温恢复正常时间，平均住院无数与甲硝唑组相似（Ｐ＞０．０５）。但脓腔缩小时间短，肝区疼痛消失早，不良反应少（Ｐ＜０．０１或０．０５）。结论：诺氟沙星治疗阿米巴肝脓肿优于甲硝唑。     

盐酸林可霉素的吸附伏安法研究

本文报道了一种测定盐酸林可霉素的灵敏的电分析方法。在０．０２ｍｏｌ／Ｌ氢氧化钠－０．０４８ｍｏｌ／Ｌ亚硫酸钠体系中，盐酸林可霉素产生一灵敏的吸附波，峰电位－１．３８Ｖ（ｖｓ．ＳＣＥ），浓度在１．０×１０~（－６）～１．２０×１０~（－５）ｍｏｌ／Ｌ之间与峰高有良好的线性关系。本文对盐酸林可霉素极谱性质和电极过程进行初步探讨，并进行了含量测定。本法具有快速、简便、灵敏、准确之特点。     

单胺菌素─喹诺酮酰胺衍生物的合成

为探索喹诺酮类化合物充当单胺菌素３位边链酸的构效关系，合成了４个未见文献报道的单胺菌素－喹诺酮酰胺衍生物（５ａ）～（５ｄ）．它们是以氧氟沙星（８）、氟罗沙星（９）或诺氟沙星前体（１－乙基－６－氟－７－氯－１，４－二氢－４－氧代喹啉－３－羧酸）（１０）通过ＤＣＣ－ＨＯＢＴ法酰化卡芦莫南母核（６）或氨曲南母核（７）得到的．初步体外抑菌试验表明：（５ａ）～（５ｄ）的最低抑菌浓度（ＭＩＣ）均大于１００ｍｇ／Ｌ     

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.