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201.
Witherington J Abberley L Briggs MA Collis K Dean DK Gaiba A King NP Kraus H Shuker N Steadman JG Takle AK Sanger G Wadsworth G Butler S McKay F Muir A Winborn K Heightman TD 《Bioorganic & medicinal chemistry letters》2008,18(6):2203-2205
A series of small molecule orally bioavailable ghrelin receptor agonists have been identified through systematic optimisation of a high throughput screening hit. 相似文献
202.
Huang J Orac CM McKay S McKay DB Bergmeier SC 《Bioorganic & medicinal chemistry》2008,16(7):3816-3824
Novel 3,5-disubstituted ring E analogs of methyllycaconitine were prepared and evaluated in nicotinic acetylcholine receptor binding assays. The desired analogs were prepared through the Suzuki-Miyaura cross-coupling reaction of methyl 5-bromo-nicotinate. The Suzuki-Miyaura cross-coupling reactions of pyridines with electron withdrawing substituents have not been extensively described previously. 相似文献
203.
Andrew Steptoe Linda Perkins-Porras Catherine McKay Elisabeth Rink Sean Hilton Francesco P Cappuccio 《BMJ (Clinical research ed.)》2003,326(7394):855
ObjectiveTo measure the effect of brief behavioural counselling in general practice on patients'' consumption of fruit and vegetables in adults from a low income population.DesignParallel group randomised controlled trial.SettingPrimary health centre in a deprived, ethnically mixed inner city area.Participants271 patients aged 18-70 years without serious illness.InterventionBrief individual behavioural counselling based on the stage of change model; time matched nutrition education counselling.ResultsConsumption of fruit and vegetables increased from baseline to 12 months by 1.5 and 0.9 portions per day in the behavioural and nutrition groups (mean difference 0.6 portions, 95% confidence interval 0.1 to 1.1). The proportion of participants eating five or more portions a day increased by 42% and 27% in the two groups (mean difference 15%, 3% to 28%). Plasma β carotene and α tocopherol concentrations increased in both groups, but the rise in β carotene was greater in the behavioural group (mean difference 0.16 μmol/l, 0.001 μmol/l to 1.34 μmol/l). There were no changes in plasma ascorbic acid concentrations or urinary potassium excretion. Differences were maintained when analysis was restricted to the 177 participants with incomes ≤£400 (€596, $640) a week.ConclusionsBrief individual counselling in primary care can elicit sustained increases in consumption of fruit and vegetables in low income adults in the general population.
What is already known on this topic
Brief interventions can be effective in increasing consumption of fruit and vegetablesBiomarkers and intention to treat analyses have seldom been used in such interventions, and few studies have targeted low income populationsWhat this study adds
Compared with nutritional counselling, brief behavioural counselling carried out by nurses in primary care led to greater increases in fruit and vegetable intake and in plasma β carotene concentrationFavourable effects were observed in low income adults living in a deprived inner city area 相似文献204.
205.
Discovery of novel dihydro-9,10-ethano-anthracene carboxamides as glucocorticoid receptor modulators
Bingwei V. Yang Wayne Vaccaro Arthur M. Doweyko Lidia M. Doweyko Tram Huynh David Tortolani Steven G. Nadler Lorraine McKay John Somerville Deborah A. Holloway Sium Habte David S. Weinstein Joel C. Barrish 《Bioorganic & medicinal chemistry letters》2009,19(8):2139-2143
A series of dihydro-9,10-ethano-anthracene-11-carboxamides as novel glucocorticoid receptor modulators is reported. SAR exploration identified compounds from this series displaying a promising dissociation profile in discriminating between transrepression and transactivation activities. 17a is a partial agonist of GR-mediated transactivation which elicits potent and efficacious transrepression in reporter gene assays. A hypothetical binding mode is provided which accounts for the induction of functional activity by a bridgehead methyl group. 相似文献
206.
Blake A. Schaeffer Daniel Kamykowski Laurie McKay Geoff Sinclair Edward Milligan 《Journal of phycology》2009,45(1):154-163
The internal lipid, carotenoid, and toxin concentrations of Karenia brevis (C. C. Davis) Gert Hansen and Moestrup are influenced by its ability to use ambient light and nutrients for growth and reproduction. This study investigated changes in K. brevis toxicity, lipid class, and carotenoid concentrations in low‐light, nitrate‐replete (250 μmol quanta · m?2 · s?1, 80 μM NO3); high‐light, nitrate‐replete (960 μmol quanta · m?2 · s?1, 80 μM NO3); and high‐light, nitrate‐reduced (960 μmol quanta · m?2 · s?1, <5 μM NO3) mesocosms. Reverse‐phase HPLC quantified the epoxidation state (EPS) of the xanthophyll‐cycle pigments diadinoxanthin and diatoxanthin, and a Chromarod Iatroscan thin layer chromatography/flame ionization detection (TLC/FID) system quantified changes in lipid class concentrations. EPS did not exceed 0.20 in the low‐light mesocosm, but increased to 0.65 in the high‐light mesocosms. Triacylglycerol and monogalactosyldiacylglycerol (MGDG) were the largest lipid classes consisting of 9.3% to 48.7% and 37.3% to 69.7% of total lipid, respectively. Both lipid classes also experienced the greatest concentration changes in high‐light experiments. K. brevis increased EPS and toxin concentrations while decreasing its lipid concentrations under high light. K. brevis may mobilize its toxins into the surrounding environment by reducing lipid concentrations, such as sterols, limiting competition, or toxins are released because lipids are decreased in high light, reducing any protective mechanism against their own toxins. 相似文献
207.
目的观察非酒精性脂肪肝(NAFLD)大鼠肝组织中PPARα基因的表达,并用PPARct激动剂进行干预,探讨其与胰岛素抵抗、脂代谢紊乱的关系。方法大鼠随机分为①正常对照组、②高脂模型组、③PPARα激动剂干预组,利用高脂饮食建立大鼠非酒精性脂肪肝模型。12周后,检测大鼠血脂、肝功能、血糖、胰岛素水平及胰岛素抵抗指数;RT-PCR法分析PPARα基因的表达;观察肝脏的形态学改变。结果PPARa激动剂可降低NAFLD大鼠转氨酶、血脂水平及胰岛素抵抗指数,可促进NAFLD大鼠中PPARa基因的表达;肝脏形态学明显改善。结论PPARα激动剂能改善NAFLD大鼠脂质代谢紊乱,有明显的保肝降酶作用,具有适度的胰岛素增敏作用。PPARα及其配体在NAFLD发病机制及治疗中的进一步深入研究,将为临床防治NAFLD提供新的思路。 相似文献
208.
目的探讨正常SD雌性大鼠性成熟前不同日龄段的脏器与促黄体生成素(LH)、促卵泡素(FSH)、雌二醇(E2)等性激素的变化及其关系。方法从生产群中取出60窝密度状态一致的SD大鼠,在不同日龄随机选取雌性大鼠,检测15、25、32、40日龄时大鼠体重、主要脏器指数,子宫、卵巢组织变化和15、25、32、40、60日龄大鼠血清LH、FSH、E2水平。结果记录了SD雌性大鼠性成熟前各脏器指数和卵巢、子宫组织变化,结果显示大鼠卵巢、子宫的增长速度大于体重的增长,而其他脏器增速大都小于体重的增长。本研究还记录了血清LH、FSH、E2水平在不同日龄段的变化规律,表明血清LH、E2浓度在32日龄时出现较为明显升高。结论不同日龄大鼠脏器指数的动态变化提示大鼠性器官在性发育早期得到机体的优先发育。血清LH、E2水平在32日龄时有了明显升高,提示性腺轴功能已经激活。60日龄大鼠血清性激素水平的波动类似于动情周期的规律性变化,推测大鼠在60日龄前即已进入性成熟,这些结果将为大鼠性发育的相关研究提供重要的参考数据。 相似文献
209.
210.
SA McKee 《Addiction biology》2009,14(1):99-107
Use of human laboratory analogues of smoking behavior can provide an efficient, cost-effective mechanistic evaluation of a medication signal on smoking behavior, with the result of facilitating translational work in medications development. Although a number of human laboratory models exist to investigate various aspects of smoking behavior and nicotine dependence phenomena, none have yet modeled smoking lapse behavior. The first instance of smoking during a quit attempt (i.e. smoking lapse) is highly predictive of relapse and represents an important target for medications development. Focusing on an abstinence outcome is critical for medication screening as the US Food and Drug Administration approval for cessation medications is contingent on demonstrating effects on smoking abstinence. This paper outlines a three-stage process for the development of a smoking lapse model for the purpose of medication screening. The smoking lapse paradigm models two critical features of lapse behavior: the ability to resist the first cigarette and subsequent ad libitum smoking. Within the context of the model, smokers are first exposed to known precipitants of smoking relapse (e.g. nicotine deprivation, alcohol, stress), and then presented their preferred brand of cigarettes. Their ability to resist smoking is then modeled and once smokers 'give in' and decide to smoke, they participate in a tobacco self-administration session. Ongoing and completed work developing and validating these models for the purpose of medication screening is discussed. 相似文献