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101.
Purpose. To determine whether the non-toxic pentameric B subunit of Cholera toxin (CTB) binding to ganglioside GM1 on both the lipid vesicles and epithelial cells may provide a means to target lipid vesicles to mucosal cells expressing surface GM1.
Methods. Sonicated lipid vesicles containing ganglioside GM1 were prepared. Inter-vesicle cross-linking due to pentameric CTB binding to these GM1 vesicles was determined with a sub-micron particle analyzer. Association of CTB to GM1 vesicles was analyzed with continuous sucrose gradient centrifugation. CTB-mediated binding of GM1 vesicles to human mucosal epithelial cells (Caco-2 and HT-29), mucous membranes of mouse trachea, and nasal tissues were detected with fluorescent labeled vesicles.
Results. An increase in lipid particle size due to binding of CTB to lipid vesicles and inter-vesicles cross-linking was detected. At a 30-to-1 mole ratio of membrane-bound GMl-to-CTB, optimum increase in GM1 vesicle aggregation, was detected. Under such conditions, all the added CTB molecules were associated with GM1 vesicles. Time course analysis showed that inter-vesicles cross linking by CTB was detectable within 10 min. and reached a maximum value at 60 min. CTB associated GM1-vesicles bind to mucosal epithelial cells HT-29 and Caco-2 with similar affinity [Kd = 7.8 × 10–4 M lipid (Caco-2) and 7.6 × 10–4 M lipid (HT-29)]. GM1 mediated binding specificity was demonstrated by blocking with anti-GMl antibody and the insignificant degree of CTB-associated GM1 vesicle binding to GM1 deficient C6 cells.
Conclusions. The CTB-mediated GM1 binding to multiple membrane surfaces provides selective localization of GM1 vesicles to GM1 expressing mucosal cells and tissues. The strategy may be useful in localizing drugs and proteins to gut and respiratory tract mucosa. 相似文献
102.
重视药物利用评价研究,开展药物利用评价活动 总被引:1,自引:1,他引:0
药物利用评价是当前医院合理用药的深入发展的重要体现,也是临床药学的重要工作之一。本文论述了药物利用评价的目的、意义、方法和进展,以及药物利用评价在医院药房中的应用,以期引起有关人员的重视。 相似文献
103.
米非司酮配伍卡前列甲酯89例与米非司酮配伍米索前列醇110例终止早期妊娠的比较 总被引:4,自引:0,他引:4
目的:比较米非司酮配伍卡前列甲酯与米非司酮配伍米索前列醇终止早期妊娠的疗效。方法:妊娠≤49d孕妇199例,年龄26±5a,随机分A组89例,B组110例。2组均用米非司酮25mg,bid,3d,于d4,A组阴道后穹窿置卡前列甲酯栓1mg。B组米索前列醇po,600μg。结果:A和B组完全流产率各为83%和93.6%,经X2检验,P<0.05;胎囊排出时间,A组4±5h,B组3±6h,2组无显著差异。结论:米非司酮配伍米索前列醇的抗早孕效果优于配伍卡前列甲酯。 相似文献
104.
海藻、甘草及其相伍用对小鼠肝药酶的影响 总被引:5,自引:0,他引:5
目的:研究海藻、甘草单煎液及其不同比例合煎,单煎后混合液以及单体A、B;C、D、E对小鼠肝药酶的影响。方法:取小鼠随机分组,分别ig给药,qd,连续4d后禁食20h,处死取肝脏,称重后制成匀浆,紫外分光光度计于450nm,490nm波长下测其光密度值,计算肝匀浆中细胞色素P-450的含量。结果:甘草、甘草与海藻合煎液及单体A,B,C,D,E均能显著提高小鼠肝匀浆中细胞色素P-450的含量,而海藻,甘草与海藻单煎后混合液未能提高小鼠肝心浆中的细胞色素P-450的含量。结论:甘草,甘草与海藻合煎液及单体,A,B,C,D,E均能显著提高小鼠肝匀浆中细胞色素P-450的含量,对肝药酶有诱导作用。 相似文献
105.
人癌干细胞集落形成测定常用双层琼脂平皿法。新法系采用园形玻璃毛细管法培养!可
以减少细胞用量及药物消耗。管内径为1.3mm,管长9.75cm,内盛15.000有核细胞/50μl,培养7~
14天。50例肿瘤活检标本生长成功率为88%,并可供化疗药物敏感性试验用。这种微量化检测具有
独特的优点,便于推广应用。 相似文献
106.
Camphor and m-cresol mixtures are used in antiseptic and anti-itching creams. No compendial method exists for these preparations. This paper reports a capillary gas chromatographic method using FID detection with 2,6-di-tert-butyl-4-methylphenol as internal standard on a 30 m×0.32 mm Supelcowax®-10 column (0.25 μm film) with helium as carrier gas. Ramped temperature programming was applied. The method allows simultaneous quantitation of camphor and m-cresol in the presence of o- and p-cresols, calamine and zinc oxide. Overall percent recoveries (±SD, n=9) of camphor, o-, p- and m-cresol from spiked placebo creams, at a labeled amount of 10 (w/w)% were 96.9±0.6, 98.2±0.6, 99.2±0.5 and 101.0±0.9%, respectively, and at a labeled amount of 1% were 96.7±0.6, 97.8±0.9, 97.8±0.6, and 100.3±1.0%, respectively. The recovery studies were carried out at ±30% of the labeled amounts. Linear peak area or height ratios were obtained (r>0.999) for camphor, o-, p- and m-cresol covering a concentration range of 10–200% of the labeled amount. Linearity (r>0.999) was also obtained for m-cresol when the relative concentration of o- and p-cresol was varied from 5 to 100% of the m-cresol concentration. The resolution between the ‘critical pair’ of p- and m-cresol was ≥1.1. The limit of quantitation was 23 pg for m-cresol and 9.3 pg for camphor using an injection split of 1:50. The repeatability (%RSD) for all compounds were <2% for peak area and <1.4% for peak height ratios. System suitability and robustness of the method were established. The method was successively applied to the assay of available commercial products and allows assay of camphor and the three cresol isomers. 相似文献
107.
Drug related hospital admissions 总被引:13,自引:0,他引:13
J. Hallas B. Harvald J. Worm J. Beck-Nielsen L. F. Gram E. Grodum N. Damsbo J. Schou H. Kromann-Andersen F. Frølund 《European journal of clinical pharmacology》1993,45(3):199-203
Summary As part of a high-intensity monitoring study of drug events as the cause of admission to departments of internal medicine, the effect of an educational intervention programme was studied. Two departments were included, one specialising in geriatrics and one that received patients by non-selected referral. The series consisted of 607 consecutive admissions studied before and 703 after the intervention. The drug events considered were adverse drug reactions and dose-related therapeutic failures, mainly due to non-compliance.A modest, statistically non-significant decrease in drug related hospital admissions (DRH) was seen, from 14% before to 13% after the intervention period. However, DRHs classified as definitely avoidable showed the significant decrease of 83%.There was no apparent relationship between the topics selected for the intervention programme and changes in the pattern of DRHs. No relationship between alterations in sales data and hospital admissions caused by a given drug could be demonstrated. A blinded external evaluation of case abstracts did not disclose any significant shift in the investigators' assessments.The intervention may have had an non-specific effect on avoidable DRHs. 相似文献
108.
3-Methoxytyramine (3-MT) is a minor metabolite of dopamine which is suggested to reflect the turnover and utilization of dopamine. A novel, isocratic HPLC method has been developed which can be used to analyse 3-MT in homogenates of rat brain without the need for additional purification procedures. Furthermore, the coulometric electrochemical detection system is sensitive enough to measure 3 pg of 3-MT (equivalent to 0.6 ng/g tissue wet weight). 3-Methoxytyramine was measured in the striatum and n. accumbens after decapitation and rapid freezing, using 3-methoxy-4-hydroxybenzylamine as the internal standard. The effects of dopaminergic and other drugs on this metabolite were examined using this method. -Methyl-p-tyrosine (200 mg/kg i.v.) produced parallel linear decreases in dopamine and 3-MT in naive rats, but not those pretreated with tranylcypromine (5 mg/kg i.p.). Methamphetamine (0.3–10 mg/kg i.p.) and amphetamine (0.3–10 mg/kg i.p.) both dose-dependently increased 3-MT in naive and tranylcypromine-pretreated rats. In naive animals, 3-MT was not altered by intraperitoneal injection of the dopamine reuptake inhibitors, bupropion (10 mg/kg) and nomifensine (10 mg/kg) or by sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg) and zimeldine (10 mg/kg). 3-Methoxy-tyramine was decreased by apomorphine (5 mg/kg i.p.) and also by large doses of the selective D2 antagonist, BRL 34778 (5 mg/kg i.p.) or
-DOPA (50 mg/kg i.p.). The selective D1 antagonist, SCH 23390 (0.1 or 5 mg/kg i.p.) was without effect. In tranylcypromine-pretreated rats, 3-MT was dose-dependently reduced and increased by apomorphine (0.01–5 mg/kg i.p.) and BRL 34778 (0.1–5 mg/kg i.p.), respectively. The drug SCH 23390 (0.1–5 mg/kg i.p.) produced much smaller increases in 3-MT which were probably mediated through the striatonigral pathway. Overall, the data suggest that measurement of 3-MT, after inhibition of monoamine oxidase, is a useful index of the release and utilization of dopamine. However, after substantial and prolonged depletion of dopamine, levels of 3-MT in naive animals are a better index. Also, the formation of 3-MT in naive rats provides a sensitive method for distinguishing between dopamine releasing agents and reuptake inhibitors. 相似文献
109.
Mark Beuger md Anthony Tommasello ms Robert Schwartz md Mary Clinton pharmd 《Journal of substance abuse treatment》1998,15(6):15-593
Forty-eight consecutive applicants and 30 known clonidine-abusing methadone patients at three methadone treatment programs were surveyed regarding their use of clonidine. Two distinct patterns of clonidine use emerged. Of 22 applicants who took clonidine illicitly, 15 used it primarily to decrease opioid withdrawal, as well as for its sedating effect. Applicants mostly obtained it from physicians, used an average dose of 0.37 mg at a time, and about one third believed clonidine to be addictive. In contrast, clonidine-using patients took clonidine primarily for its psychoactive effects, including the interaction with methadone, in addition to decreasing opioid withdrawal. Patients obtained clonidine frequently on the street and from family or friends, but less from physicians. The average reported dose for patients was 0.6 mg. The vast majority of these patients felt clonidine was addictive. Our findings, when coupled with the risk inherent in clonidine overdose, suggest that further research into the identification and treatment of clonidine abuse among methadone patients is warranted. 相似文献
110.
Walter G. Sannita Luisa Lopez Lino Maggi Guido Rosadini 《Documenta ophthalmologica. Advances in ophthalmology》1988,70(1):89-96
L-acetylcarnitine is a compound with cholinergic properties and putative action on the visual system and the glucose metabolism. Ten healthy, emmertropic volunteers (age range: 21 to 28 years) were studied. Each subject was administered 5, 10, and 30 mg/kg acute intravenous doses of L-acetylcarnitine and matching placebo. Retinal oscillatory potentials to full-field flash stimulation were recorded before and 30, 60, and 120 min after administration. A systematic reduction of the implicit time of the P2 and N2 oscillatory potential components was observed after administration of the 10 and 30 mg/kg doses: significant changes were not evident at the 5 mg dose or after placebo. The latency reduction was significantly correlated with the postdrug increment of the L-acetylcarnitine plasma concentration. No other systematic modification in latency of amplitude was observed.The results were presented in part at the XXV I.S.C.E.V. Symposium, Sarasota (Florida), April 26–30, 1987. 相似文献