荧光光谱法研究安非他酮与人血清白蛋白的相互作用

目的 研究安非他酮与人血清白蛋白(human serum albumin,HSA)的相互作用。方法 通过荧光光谱法研究安非他酮对HSA的荧光猝灭光谱和同步荧光光谱的影响。由Stern-Volmer方程确定安非他酮对HSA的荧光猝灭机制,双对数方程确定反应结合位点和结合常数。根据热力学方程讨论两者间主要的作用力类型。结果 荧光猝灭光谱显示,安非他酮对HSA有猝灭作用,在17 ℃和37 ℃时的猝灭速率常数分别为5.714 8×10³和3.126 1×10³ L·mol^-1·s^-1,反应前后的焓变和熵变均<0,结合点数为1。结论 安非他酮对HSA的猝灭过程为静态猝灭,二者间的结合力主要为氢键和范德华力。     

荧光猝灭法研究二氢槲皮素和二氢杨梅素与牛血清白蛋白的相互作用

目的 研究二氢槲皮素和二氢杨梅素与牛血清白蛋白(BSA)的相互作用。方法 运用荧光光谱法结合Stern-Volmer方程和Line Weaver-Burk双倒数函数计算出BSA与二氢槲皮素和二氢杨梅素相互作用的猝灭常数和结合常数,通过反应前后热力学参数如焓变ΔH和熵变ΔS的大小对作用力类别进行判断。结果 测得二氢槲皮素与BSA在不同温度下的结合常数293 K为2.27×10⁴ L·mol-1,298 K为2.06×10⁴ L·mol-1,303 K为1.89×10⁴ L·mol-1,二氢杨梅素与BSA在不同温度下的结合常数293 K为2.43×10⁴ L·mol-1,298 K为2.39×10⁴ L·mol-1,303 K为2.13×10⁴ L·mol-1。确定其使牛血清白蛋白荧光猝灭的过程为静态猝灭过程,通过热力学参数确定其结合力主要为疏水作用。结论 应用荧光猝灭法了解二氢槲皮素和二氢杨梅素与牛血清白蛋白之间有较强的结合反应,结合力以疏水作用力为主。     

抗凝药物华法林与牛血清白蛋白相互作用光谱研究

采用紫外-可见吸收光谱和荧光光谱，在生理pH条件下，研究华法林与牛血清白蛋白的相互作用。探讨华法林对于牛血清白蛋白的荧光猝灭机制。结果表明华法林对牛血清白蛋白的猝灭作用为动态猝灭过程。猝灭常数在16 ℃和37 ℃分别为6.05×10⁴ L·mol^-1和6.14×10⁴ L·mol^-1。根据Fster的偶极-偶极无辐射能量转移理论，求得牛血清白蛋白-华法林的能量转移效率E为0.37，两者间的最近距离r为3.15 nm。     

荧光光谱法研究顺铂与牛血清白蛋白的键合

摘 要 目的：探讨在人体生理条件下顺铂与牛血清白蛋白(BSA)的结合作用。 方法: 采用荧光光谱法研究顺铂与BSA的作用机制;考察其结合常数、结合位点数和作用力类型;考察顺铂对BSA构象的影响。结果: 顺铂对BSA的猝灭过程是形成基态复合物的静态猝灭,顺铂与BSA结合位点数和结合常数分别为1.36×10⁴ L·moL^-1和0.991,两者以氢键和范德华力为主。同步荧光表明两者结合作用影响色氨酸残基所处的微环境。结论:顺铂能与BSA结合并改变BSA的构象。     

荧光光谱法研究肼黄与人血清白蛋白的结合性质

目的 研究肼黄与人血清白蛋白（HSA）间的结合性质。方法 采用荧光猝灭法对肼黄与人血清白蛋白间相互作用进行研究。结果 肼黄可以使HSA的内源荧光发生猝灭现象。肼黄与HSA相互作用的热力学参数计算结果为ΔG⁰<0、ΔH⁰<0、ΔS⁰>0。华法林的加入可使HSA-肼黄体系的荧光强度明显降低。结论 肼黄以形成HSA-肼黄复合物的静态猝灭机制与HSA发生相互作用。二者形成HSA-肼黄复合物的过程是自发进行的,疏水作用力和氢键在形成HSA-肼黄复合物的过程中发挥主要作用。肼黄在HSA上的结合位点是与华法林相同的siteⅠ位。     

盐酸西布曲明与牛血清白蛋白结合作用的光谱学研究

目的运用光谱学方法研究在生理pH值条件下盐酸西布曲明与牛血清白蛋白之间的结合作用。方法 通过荧光法和吸收光谱法确定了盐酸西布曲明对牛血清白蛋白的荧光猝灭机制。依据Scatchard方程测定了不同温度下该结合反应的结合常数和结合位点数。根据热力学方程讨论了两者间的主要作用力类型。结合同步荧光分析了盐酸西布曲明对牛血清白蛋白构象的影响。结果盐酸西布曲明对牛血清白蛋白的荧光猝灭机制为静态猝灭。在8，25和37 ℃时盐酸西布曲明与牛血清白蛋白的结合常数分别为1.21×10⁵，8.31×10⁴和6.97×10⁴ L·mol^-1，结合位点数均为1。结合反应的热力学参数为ΔH=-9.70 kJ·mol^-1，ΔS=56.41 J·mol^-1·K^-1。结论 两者结合的主要作用力类型是静电作用。盐酸西布曲明在体内能够被血清蛋白存储和转运且结合时对蛋白构象无影响。     

荧光光谱法研究昂丹司琼与人血清白蛋白的相互作用

目的利用荧光光谱法研究昂丹司琼(OND)与人血清白蛋白(HSA)的相互作用。方法采用荧光光谱法。结果在296K和310K时OND与HSA的结合常数分别为3.24×104L/mol,4.68×104L/mol,热力学参数ΔH为20.08kJ/mol。结论 OND对HSA的荧光猝灭机制主要为静态猝灭,二者有一个结合位点,其作用力类型以疏水作用力为主。     

巴罗沙星与DNA的相互作用及Mg2+的影响

目的研究巴罗沙星与DNA的分子作用机制和Mg²⁺对巴罗沙星与DNA相互作用的影响。方法利用荧光光谱研究巴罗沙星与DNA的作用强度并计算热力学数据ΔH；利用紫外光谱、黏度测定、竞争实验、与变性DNA作用的比较等方法确定巴罗沙星与小牛胸腺DNA的相互作用方式；利用荧光光谱考察Mg²⁺对巴罗沙星与小牛胸腺DNA相互作用的影响。结果DNA对巴罗沙星的荧光猝灭常数为(5.43±0.07)×10³ L·mol^-1，ΔH=-8.03 kJ·mol^-1；Mg²⁺使巴罗沙星与DNA的作用增强。结论巴罗沙星以沟槽键合方式与DNA相互作用；Mg²⁺对巴罗沙星与DNA的结合有中介作用。     

一种氨基葡萄糖棉酚Schiff碱衍生物的制备及其抗HIV-1病毒活性

摘 要 目的：确定1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱结构及其优势构象,并探讨其抗HIV-1病毒活性。方法: 制备1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱, 并利用红外光谱, 核磁波谱技术和PM6半经典计算等方法对其结构进行解析;采用HIV-l/IIIB-/TZM-bl细胞指示系统测定其抗HIV-1病毒活性。结果: 光谱分析表明1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱新化合物具有烯胺-烯胺结构特征,并归属了所有碳原子和氢质子化学位移; PM6研究表明1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱烯胺-烯胺和亚胺-亚胺构型的生成热分别为-4 168.415 kJ·mol^-1和-4 150.080 kJ·mol^-1,烯胺 烯胺构型在能量上更有利,并确立了其优势构象,分子内氢键使其更为稳定,与光谱分析结果一致;新化合物显示了较强的抗艾滋病毒活性,可能作用在病毒感染细胞的进入阶段。结论:1,3,4,6-四-O-乙酰基-β-D-氨基葡萄糖棉酚Schiff碱以烯胺 烯胺构型存在,具有一定抗艾滋病毒活性。     

荧光光谱法分析盐酸哌唑嗪与牛血清白蛋白的结合作用

目的研究不同温度下盐酸哌唑嗪与牛血清白蛋白(BSA)间的相互作用及其作用机制。方法荧光光谱法。结果荧光光谱法测定盐酸哌唑嗪与BSA在25℃和37℃反应的结合常数K均是2.0×10⁴L·mol^-1,结合位点数n分别为1.19,1.14,热力学参数为(37℃)ΔH=0,ΔG=-25.52kJ·mol^-1,ΔS=0.082kJ·mol^-1·K^-1,盐酸哌唑嗪的加入影响了BSA的构象;依据Frster非辐射能量转移机制,得到盐酸哌唑嗪与BSA之间的结合距离和能量转移效率分别为r=4.69nm,E=0.078。结论盐酸哌唑嗪与BSA在实验浓度范围内形成了具有一定结构的复合物,且它们之间的作用力以静电作用力为主。     

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.