阿尔泰狗哇花挥发油的气相色谱-质谱联用分析

目的分析植物阿尔泰狗哇花的精油成分。方法采用常规水蒸气蒸馏法提取精油，运用气相色谱质谱联用（GC-MS）对其成分进行分析，用气相色谱面积归一化法测定计算了各成分的相对百分含量。结果经GC-MS分析共分离出54个峰，鉴定出38种化合物，占总峰面积的91.7％。主成分为单萜和倍半萜，占挥发油检出成分的73．6％，其中含量较大的成分有大根香叶烯（20．1％）、石竹烯（7．29％）、1，1，4，7-四甲基-八氢化-1氢-环丙基工薁（7．18％）、β-蒎烯（5．40％）、β-水芹烯（3．77％）、苎烯（3．02％）。另外还含有乙酸乙酯（7．62％）、甲酸乙酯（3．65％）、斯巴醇（3．42％）等成分。结论阿尔泰狗哇花精油中含有多种药理活性成分，有综合开发利用的价值。     

藏药甘毕二汤二氧化碳超临界流体萃取精油化学成分研究

目的:研究藏药甘毕二汤二氧化碳超临界流体萃取精油的化学组成及相对含量。方法:采用气相色谱-质谱联用方法分离鉴定甘毕二汤二氧化碳超临界流体萃取精油化学成分并测定其相对含量。结果:甘毕二汤二氧化碳超临界流体萃取精油得率为5.9%,分离得到48个色谱峰,鉴定出43种成分,主要成分是桉叶油二烯-5,11(13)-内酯-8,12、胡椒碱、β-谷甾醇、α-蛇麻烯、8-十七烯、9-十八炔酸甲酯、反亚油酸甲酯、榄香醇、正十六烷、花生四烯酸甲基酯、正十四烷、反式石竹烯、(Z,Z,Z)-9,12,15-十八烷三烯酸乙酯、1,1-二甲基萘等。结论:甘毕二汤二氧化碳超临界流体萃取精油中富含烃、萜、酯和醇等组分,其中桉叶油二烯-5,11(13)-内酯-8,12和胡椒碱的相对含量之和占精油含量的39.40%。     

气相色谱-质谱和化学计量学解析法分析防风挥发油成分

目的：定性、定量分析防风挥发油成分。方法：采用气相色谱-质谱法进行检测，通过化学计量学解析法对重叠色谱峰进行分辨，实现防风挥发油成分的定性、定量分析。结果：防风挥发油成分鉴定了45个，占挥发油成分总含量的89．15％。结论：防风挥发油主要成分是镰叶芹醇（11．24％），苯亚甲基苯甲醛（9．40％），正辛醛（6．76％），正己醛（3．16％），2，3，5，6，7，8，8a-八氢-1，4-二甲基-7-（1-甲基乙烯基）莫（2．13％），2，4-癸二烯醛（1．83％）和正庚醛（1．71％）．     

甘肃产独活及牛尾独活挥发油成分的气-质联用分析

目的分析甘肃产独活Angelica pubescens Maxim．f.biserr-ata Shan et Yuan及牛尾独活Heraeleum moellendoffii Hance的挥发油成分。方法采用GC—MS方法分离和鉴定挥发油成分，并用面积归一化法进行定量分析。结果从独活挥发油中分离出55个化合物，占挥发油总量的94．196％；从牛尾独活挥发油中分离鉴定鉴定出47个化合物，占挥发油总量的81．657％。结论独活挥发油主要成分为α-蒎烯(20．295％)、1-甲基4-异丙基苯(15．568％)、3-甲基-壬烷(5．904％)等；牛尾独活挥发油主要成分为β-蒎烯(24．321％)、α-蒎烯(8．167％)、1-甲基4-异丙烯基-环己烯(8．061％)等。     

药对陈皮—干姜与其单味药挥发性成分的比较分析

目的:比较分析药对陈皮-干姜与其单味药的挥发性成分.方法:采用水蒸气蒸馏法分别提取陈皮,干姜药材及药对挥发性成分,应用气相色谱-质谱联用(GC-MS)技术对各样品中的挥发性成分进行比较分析,并采用峰面积归一化法计算百分含量.结果:从陈皮挥发性成分中检出的4-异丙基甲苯、D-柠檬烯、壬醛、大根香叶烯等成分和干姜挥发性成分中检出的甲基庚烯酮、α-法尼烯、5-甲基-2-(1-甲基乙烯基)-4-己烯-1-醇乙醇酯、α-长叶蒎烯等成分在药对挥发油中均未检出;而药对陈皮-干姜中新增成分冰片、2-甲基丙酸-3,7-二甲基-2,6-辛二醇酯、β-桉叶醇、肉桂苯氨基甲酸酯等.结论:药对陈皮-干姜配伍后挥发性化学成分与单味药相比有明显差异.     

桔皮挥发油、几种人工合成香精中α-柠檬烯含量的比较

目的 观察桔皮挥发油、几种人工合成香精中α-柠檬烯不同含量结果。方法 采用气相色谱-质谱检测挥发油中α-柠檬烯．结果 芦柑皮挥发油和3种人工合成香精经色谱分离出14-50多个峰不等，主要成分均为α-柠檬烯，其它各成分的含量均在15％以下。其中以香橙油香精含α-柠檬烯量最多(89．49％)，其次为桔子油香精(88．3％)。结论 挥发油中80％是α-柠檬烯，若能用人工合成的香精代替天然桔皮挥发油中的α-柠檬烯，可解决资源问题．若有人工合成品，对研究α-柠檬烯的药理作用取材更为方便。     

柴胡桂枝汤挥发油的GC-MS分析及对人肺腺癌A549细胞体外增殖的抑制作用研究

目的:研究复方柴胡桂枝汤挥发油的组成成分,并评价其对人肺腺癌A549细胞体外增殖的抑制作用。方法:根据2015年版《中国药典》(四部)通则2204挥发油测定法中甲法提取柴胡桂枝汤中的挥发油。采用气相色谱-质谱联用法(GC-MS)结合Kováts指数分析其挥发油成分,并采用峰面积归一化法计算各成分的相对含量。以不同质量浓度顺铂(4、8、16、32、64 mg/L)为阳性对照,采用MTT法检测不同质量浓度柴胡桂枝汤挥发油(25、50、100、200、400 mg/L)作用48 h后对A549细胞体外增殖的抑制作用;另设阴性对照组(加细胞但不加药物)。结果:从挥发油中共分离出71个成分,鉴定出其中59个成分,其峰面积之和占总峰面积的84.99%。其中,相对含量较高的成分为芳姜黄烯(17.65%)、β-甜没药烯(9.57%)、β-罗勒烯(7.05%)、α-姜黄烯(5.35%)、2,5-二甲基苯甲醛(4.24%)、异丁酸芳樟酯(2.70%)、α-雪松烯(2.48%)、δ-杜松烯(2.07%)。与阴性对照组比较,4~64 mg/L顺铂组和25~400 mg/L柴胡桂枝汤挥发油组细胞的增殖率均显著降低(P<0.05);顺铂和柴胡桂枝汤挥发油对A549细胞体外增殖的半数抑制浓度分别为10.150、73.526 mg/L。结论:柴胡桂枝汤挥发油中主要以芳姜黄烯、β-甜没药烯、β-罗勒烯、α-姜黄烯等成分为主,其对A549细胞的体外增殖具有一定的抑制作用。     

GC-MS法分析黄皮叶和假黄皮叶中挥发油成分的差异

目的:分析黄皮叶和假黄皮叶中挥发油成分的差异。方法:通过水蒸气蒸馏法分别提取黄皮叶和假黄皮叶中的挥发油。然后采用气相色谱-质谱联用(GC-MS)技术进样分析获得总离子流图,采用HPMSD化学工作站对总离子流图中各色谱峰进行质谱扫描后,通过检索比对图谱库NIST Version 1.7鉴定两种药材中挥发油的化学成分,并采用峰面积归一化法计算各成分的相对质量分数。结果:从黄皮叶、假黄皮叶挥发油中分别鉴定出了43、31个成分,相对质量分数总和分别为97.59%、98.57%。其中,相对质量分数超过1%的成分分别有19、18个,均主要为倍半萜类;相对质量分数超过5%的挥发油成分分别有7、5个,在黄皮叶挥发油中主要以(-)-斯巴醇(12.35%)和(E)-5-{(1R,3R,6S)-2,3-二甲基三环[2.2.1.02,6]庚烷-3-基}-2-甲基戊-2-烯醛(14.70%)为主,在假黄皮叶中主要以(E)-倍半水合桧烯(24.94%)和1-(1,5-二甲基-4-己烯基)-4-甲基-苯(16.15%)为主。两者中共有挥发油成分4个,分别为α-蛇麻烯、(E)-5-{(1R,3R,6S)-2,3-二甲基三环[2.2.1.02,6]庚烷-3-基}-2-甲基戊-2-烯醛、石竹烯氧化物和(-)-斯巴醇,两者中共有成分含量差异均不大。结论:黄皮叶和假黄皮叶挥发油中成分类型基本相似,但具体成分组成和含量差异较大,不可相互替代使用。     

青蒿精油化学组成及其生态类型相关性研究

目的:研究重庆永川、湖南湘潭、山东招远3个不同产地野生青蒿精油的化学组成;探讨青蒿精油化学组成及其生态类型的关系。方法:水蒸气蒸馏法提取精油,GC-MS法分析精油的化学组成。结果:从3个产地的青蒿精油中分别鉴定出44,50,39个化合物,占精油总量的85.58%,82.33%,94.83%;3个产地的青蒿精油含有19化合物相同,其中蒿酮(11.32%,0.10%,57.48%)、樟脑(10.05%,8.20%,2.43%)、石竹烯(14.83%,6.26%,3.55%)和大根香叶烯-D(13.44%,6.14%,2.07%)的相对含量差别明显。结论:实验结果证实山东招远青蒿属于观赏类型,湖南湘潭青蒿属于混合类型;而重庆永川青蒿属于混合类型和富青蒿素类型之间的过渡类型,更趋向于后者。     

GC—MS蒙古苍耳挥发油成分分析

目的对蒙古苍耳挥发油成分进行分析研究。方法采用超声波提取法提取蒙古苍耳中的挥发性成分,GC毛细管柱色谱法进行分离,质谱检测器进行分析,峰面积归-化法确定其相对含量,气相色谱-质谱联用技术辅助人工检索鉴定其化学成分。结果从蒙古苍耳的挥发油中分离鉴定出23种化学成分,主要成分有异硫氰酸甲酯（2．92％）,双（三甲基硅基）雌二醇（1．85％）,维生素E（1．33％）,五味子醇甲（1．78％）,秋酰胺（3．09％）,谷甾醇（1．63％）,4,4-二甲基胆甾（15．54％）,秋水仙碱（1．86％）,3,7,11,15-四甲基-十六醇（13．34％）,仪-亚麻酸（16．02％）,1-亚麻酸（30．12％）,粪甾烯（2．56％）,碱性艳绿（4．49％）,豆甾醇（1．09％）,上述14种成分含量占总含量的99．7％。结论蒙古苍耳挥发性成分中亚麻酸总含量最高,占挥发性成分总量的46．14％。     

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.     

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.     

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.     

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.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.     

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.     

Benzodiazepines,amnesia and sedation: Theoretical and clinical issues and controversies

The amnestic effect of benzodiazepines, first described in 1965, and the subsequent attempts to identify the precise nature of this effect, are reviewed. The difficulty in deciding to what extent this effect is secondary to the sedative action of these drugs is shown by the lack of agreement between studies. Nevertheless, it is concluded that, given the right experimental design, all benzodiazepines can be shown to cause an anterograde amnesia which is probably primarily a result of reduced attention or rehearsal and secondary to sedation. Its onset, degree and duration are influenced by dose, rate of absorption, route of administration, potency and the receptor occupancy rate of the particular benzodiazepine involved, but plasma elimination t_½ appears to be relatively unimportant. The clinical relevance of this for the long-term use of hypnotics and anxiolytics is not clear. Tolerance appears to be greater than for the anxiolytic but less than the sedative or anticonvulsant effect of benzodiazepines. It seems that transient amnestic effects could occur in chronic users related to post-dose, peak benzodiazepine levels. The great variability in individual response means that transient amnesia is a potential adverse drug reaction in certain individuals taking benzodiazepines.     

Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination

The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers.The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml^–1·h, and from 63.4 to 74.6 ng·ml^–1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide.The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril.Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.