环丙沙星在老年慢性阻塞性肺病患者多次给药的药动学研究

应用微生物法测定６名老年慢性阻塞性肺病患者（ＣＯＰＤ）多次口服环丙沙星片后的血清药物浓度，药物体内过程符合一室模型，其主要药动学参数分别为：Ｔ１／２＝５．１±１．１ｈ；Ｖｄ／Ｆ＝７±４Ｌ／ｋｇ；（Ｃ∞）ｍａｘ＝２．７±１．０μｇ／ｍｌ；Ｔ′ｐ＝１．０±０．４ｈ，测定方法平均回收率为１０１．６％     

高效液相色谱法与紫外法测定慢性阻塞性肺病患者茶碱血药浓…

本文用高效液相色谱法（ＨＰＬＣ）和双波长紫外分光光度法（ＵＶ）平行测定了２１例慢性阻塞性肺病（ＣＯＰＤ）患者的血清茶碱浓度，共１２３例次，两种方法之间有良好的线性关系（ｒ＝０．９７６１，Ｐ〈０．０１），但ＵＶ法较ＨＰＬＣ法测得的血清茶碱浓度低（△Ｃ＝－０．６±１．６ｍｇ／Ｌ，ｎ＝１２３，Ｐ〈０．０５），药物动力学研究表明：两种方法所得药－时曲线均符合一房室模型，血药浓度的差异并不影响茶碱的主要药动     

咪哒唑仑在两个年龄组的药物动力学

对健康男性较高年龄及青年志愿者各７例，分别单次快速静滴０．０８ｍｇ／ｋｇ及０．１２ｍｇ／ｋｇ咪哒唑仑后，进行了药物动力学研究。结果两组药物动力学均成二室模型。较高年龄组比青年组的室间转运速率常数Ｋ１２、末相半衰期Ｔ１／２β和平均滞留时间ＭＲＴ０－∞均明显增大，两组Ｋ１２分别为７±６ｈ和２．８±１．４ｈ（Ｐ＜０．０５），Ｔ１／２β为４．０±１．７ｈ和２．１±０．６ｈ（Ｐ＜０．０１），ＭＲＴ０－∞为５．２±１．８ｈ和２．５±０．７ｈ（Ｐ＜０．０１）；而总清除率ＣＬｓ较高年龄组比青年组明显减小，分别为０．１７±０．０３Ｌ／（ｋｇ·ｈ）和０．２８±０．０８Ｌ／（ｋｇ·ｈ）（Ｐ＜０．０１）。且中国人ＣＬｓ较欧洲人为低。提示年龄增大对咪哒唑仑的清除能力下降，中国男性老年人给药剂量和给药间隔应适当调整。     

盐酸特拉唑嗪胶囊人体生物利用度及药物动力学研究

目的：对盐酸特拉唑嗪胶囊的人体内生物利用度进行研究。方法：单剂量口服盐酸特拉唑嗪胶囊和片剂２ｍｇ。血药浓度采用ＨＰＬＣ测定，数据用３Ｐ８７计算药动学参数。结果：盐酸特拉唑嗪胶囊剂的药动学参数：Ｋａ为８．２±４．０ｈ－１，Ｔ１／２为８．２±２．５ｈ，Ｔｍａｘ为０．６１±０．１１ｈ，Ｃｍａｘ为４３．５±８．５ｎｇ·ｍｌ－１，ＡＵＣ为３６７．４±３４．６ｎｇ·ｈ·ｍｌ－１；盐酸特拉唑嗪片剂的药动学参数：Ｋａ为６．４±７．４ｈ－１，Ｔ１／２为７．４±２．１ｈ，Ｔｍａｘ为０．９±０．４ｈ，Ｃｍａｘ为４３．１±４．８ｎｇ·ｍｌ－１，ＡＵＣ为３７１．３±４４．４ｎｇ·ｈ·ｍｌ－１。结论：两种剂型的药物动力学参数之间差异均无显著性（Ｐ＞０．０５），胶囊剂的相对生物利用度为９９．８８％。     

羟乙桂胺在肌肉挛缩患者及健康志愿者体内的药物动力学

９名肌肉挛缩患者和６名健康志愿者口服羟乙桂胺片１５ｍｇ／ｋｇ，用ＨＰＬＣ测定血药浓度并计算动力学参数。９名肌肉挛缩患者口服后的达峰时间Ｔｍａｘ（约１ｈ），峰浓度Ｃｍａｘ（５．５±０．８μｇ／ｍｌ）；ｋａ（１．１９±０．１４ｈ－１），ｔ１／２α（１．０８±０．３１ｈ），ｔ１／２β（３．３７±１．０５ｈ），与健康志愿者无显著差异（ｐ＞０．０５）。     

应用Bayesian反馈法预测阿替洛尔药物动力学参数及血药浓度

应用Ｂａｙｅｓｉａｎ反馈法预测２１例高血压病人，口服阿替洛尔的个体药动学参数及稳态血药浓度（Ｃｐｓｓ）并与经典药动学方法估算结果作比较，结果表明本法的Ｔ１／２为６．０±１．７ｈ，Ｖｄ为１．４３±０．１３Ｌ／ｋｇ，ＣＬ为１７２±３４ｍｌ／（ｈ·ｋｇ）；经典法的Ｔ１／２为６．８±２．４ｈ，Ｖｄ为１．４５±０．５６Ｌ／ｋｇ，ＣＬ为１６４±８５ｍｌ／（ｈ·ｋｇ）。两者无显著性差异（Ｐ＞０．０５）。两法所测得Ｃｐｓｓ有较好相关性（ｒ＝０．９９３）。     

氨氯地平片在健康人和高血压患者中的药物动力学

采用反相高效液相色谱法测定了健康志愿者及高血压患者共３３名单剂量口服５ｍｇ苯磺酸氨氯地平片后的血清药物浓度，研究了该药在中国人体内的药物动力学。经ＰＫＢＰ－Ｎ１程序拟合表明，氨氯地平主要呈现二房室模型。其主要药动学参数分别为：健康人Ｔ１／２α＝０．６±０．５ｈ，Ｔ１／２β＝３５±９ｈ，Ｔｍａｘ＝８±４ｈ，Ｃｍａｘ＝２．４±０．８ｎｇ／ｍｌ；中青年高血压患者Ｔ１／２α＝０．６±０．４ｈ，Ｔ１／２β＝３６±９ｈ，Ｔｍａｘ＝１１±４ｈ，Ｃｍａｘ＝２．３±１．２ｎｇ／ｍｌ；老年高血压患者Ｔ１／２α＝０．４９±０．３３ｈ，Ｔ１／２β＝４２±１４ｈ，Ｔｍａｘ＝１０±４ｈ，Ｃｍａｘ＝２．８±１．４ｎｇ／ｍｌ。结果表明，中国人体内的氨氯地平药动学参数与报道的外国人相似。     

口服茶碱缓释胶囊的药物动力学

采用荧光偏振免疫法（ＦＰＩＡ），对１２名老年慢性阻塞性肺病（ＣＯＰＤ）患者口服单剂量和多剂量茶碱缓释胶囊（ＰＴ）测定经时血药浓度并计算药物动力学参数。结果表明，单剂量组口服ＰＴ后Ｔｍａｘ＝７．０±６．０ｈ，Ｃｍａｘ＝６．８±２．６ｍｇ·Ｌ－１；多剂量组连续口服ＰＴ后Ｔｓｓｍａｘ＝４．０±１．８ｈ，Ｃｓｓｍａｘ＝１６．５±２．６ｍｇ·Ｌ－１。     

盐酸伪麻黄碱在人体中的药物动力学

采用反相高效液相色谱外标法测定人血清中伪麻黄碱浓度，并测定８例志愿受试者伪麻黄碱血药浓度，并计算分析药物动力学参数，结果单剂量口服９０ｍｇ盐酸伪麻黄碱后，药时曲线呈一室模型。Ｔｍａｘ＝１．７±１．１ｈ，Ｃｍａｘ＝３６４±９４ｎｇ·ｍｌ－１，ＡＵＣ（０～∞）＝２６６２±３０３（ｎｇ·ｈ·ｍｌ－１），Ｔ１／２＝４．０±１．０ｈ，Ｋａ＝２．４±１．４ｈ－１，Ｋｅ＝０．１９±０．０４ｈ－１，Ｖｄ＝０．１９±０．０５ｍｇ，Ｃｌ＝０．０３±０．０１ｍｇ·ｈ－１。     

高效液相色谱法测定静注吡洛地尔兔血药浓度及药物动力学参数

本文应用反相高效液相色谱法测定兔静注吡洛地尔（１５ｍｇ／ｋｇ）血药浓度，样品用正庚烷提取。流动相以１０％三乙胺：甲醇液（甲醇：水＝９：１）＝５：９５。紫外检测波长为２５４ｎｍ，回收率８１．４％，日内和日间的ＲＳＤ值为２．４％、３．５％。最低检测血浓为２０ｎｇ／ｍｌ。用３Ｐ８７程序拟合为二室模型。α＝３．０８ｈ－１，β＝０．１８ｈ－１，Ｔ１／２＝４．０７ｈ，Ｋ１０＝０．９１ｈ－１，Ｋ１０＝０．６１ｈ－１，Ｖｃ＝１１．４５ＡＬ／ｋｇ，ＣＬ＝６．７３Ｌ／（ｋｇ·ｈ），ＡＵＣ＝２．２１（μｇ·ｈ）／Ｌ。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.