2010~2014年某大型综合型医院青年科学基金申报资助分析

目的 探讨青年科学基金获资助的必要条件。方法 对2010~2014年某大型综合型医院申请和中标的青年科学基金数据进行统计描述和统计分析,分析基金申请人员和获资助人员基本特征。结果 ①此大型医院近5年共申请青年科学基金543项,中标132项,平均资助率为24.31%;②项目负责人男女性别分布平均,以中级职称居多,重点学科中标率高;③77.27%的科研人员获得青年基金前已经发表过1~3篇SCI论文。结论 科研人员的研究基础对获青年科学基金资助越来越重要。     

NSFC药物学与药理学学科2000年度受理与资助项目

作为我国科教兴国方针的实施措施之一,国家自然科学基金委员会2000年度科学基金经费在1999年度约10亿元的基础上又有较大幅度的增长,达到约13亿元人民币。今后两年还将有较大幅度的增加,到2002年科学基金经费将不少于20亿元人民币。我国科学家从事的基础研究工作将会得到更有力的支持。同时,“十五”期间国家自然科学基金委员会还将在具体管理和项目评审办法方面进行新的改革和探索,积极支持和鼓励有我国特色和源头创新性的科学研究,以使我国科学研究的总体水平在21世纪初期能进一步缩小与发达国家的差距,在某些方面形成我国的特色和优势领…     

互联网科研基金与临床试验信息网站

1科研基金信息网站科学基金是医学工作者获得研究资助的主要来源。基金资助信息主要可通过学术组织网站和科学基金会网站获取。本文介绍几个国内外主要科学基金组织的网站和网址。GrantsNet网站是一个检索方便、更新及时的生物医学研究与科学教育基金资助项目数据库。对于医学研究者来说,其丰富的资源和方便的检索可以帮助他们迅速查询到所需要的信息,有助于了解和紧跟研究潮流,并及时获得研究与教育基金。此外,该网站还提供了帮助年轻学者如何获得基金的指南信息,以及基金资助新闻信息、学者间交流信息的讨论组等服务功能。1.1美国基金网…     

某三甲医院提升国家自然科学基金申报水平的激励措施及效果评价

目的 调整科研项目激励措施，提升医院职工申报国家自然科学基金项目的积极性和质量。方法 收集2010—2021年某三级甲等医院国家自然科学基金项目的申报与立项数据，对比2016年调整激励措施前后数据变化，评价调整激励措施后的效果。结果 调整措施后，该医院的国家自然科学基金申报项目数量明显提高，且科研人员申报青年科学基金等全国竞争性项目的积极性明显提升，增长率远大于地区科学基金项目；立项数量稳中有升，资助经费明显增长；项目申报结构、立项结构均得到优化；该医院整体科研水平显著提升。结论 该院制定的科研项目调整措施效果显著。     

医药类基础研究 项目的绩效评价初探

为探索对基础研究项目进行绩效评价的方法，本文结合1988年底对3所医科大学1991－1995年间获得国家自然科学基金资助的医药类面上项目的投入产出情况调查，从项目参加者情况、经费使用、论文产出、获奖、专利和产业化、获得后续资助及人才培养等方面比较了3所高校的项目投入产出情况；作者对基础研究绩效评价的方法进行了讨论，指出绩效评价需要联合多种指标进行综合考查，基础研究项目要重点突出创新性和人才及其研究能力的培养方面的评价。     

我国学者揭示代谢与免疫新机制

在国家自然科学基金优秀青年科学基金（项目编号：31522020）和面上项目（项目编号：31270017）等资助下,浙江大学医学院王迪教授通过构建动物疾病模型,结合免疫学、细胞生物学和生物化学等研究手段,发现胆酸可以通过抑制NLRP3炎症小体从而改善炎症性疾病,如脓毒症、腹腔炎以及2型糖尿病等的发生,揭示了脂代谢通路蛋白参与炎症性疾病发生发展的新机制。     

关于评选第14届中国药学会-施维雅青年药物化学奖和专项研究资助项目的通知

<正>中国药学会-施维雅青年药物化学奖和专项研究资助项目是由中国药学会与法国施维雅研究院共同设立,每年评选一次,旨在鼓励我国优秀青年药物化学工作者立足于国内,致力于新药研究。2011年第14届奖项推荐评选工作已经开始,现将有关事宜通知如下。根据设奖宗旨和国内药物化学学科发展的实际情况,2011年奖励办法为:(1)继续面向全国,奖励3名从事药物化学研究的青年药物化学(合成药物和天然药物)学者;获奖者每人可获得奖金15 000元人民币、奖杯和证书。(2)面向边远地区的专项资助项目,资助1项研究课题,经费为50 000元人民币,2年内完成;并颁发专项资助项目证书。(3)如专项资助项目空缺,则青年药物化学奖奖励名额为5名。     

政府研发资助、内部研发投入与制药企业创新绩效的关系研究

目的:为提高政府对制药企业研发资助效果、增加企业内部研发投入和提高创新绩效提供参考。方法:在假设的基础上,构建政府研发资助、内部研发投入与创新绩效关系的理论模型,采用回归分析和中介效应分析方法,以江苏省的制药企业为研究对象进行实证研究。结果与结论:所设计的量表具有良好的信度和效度,经实证检验后得到最终的模型,结合各相关系数结果表明除假设3外其余各项假设均可获得验证。其中,政府研发资助对制药企业内部研发投入和创新绩效均存在促进效应,内部研发投入在政府研发资助与创新绩效之间起到完全中介作用,即政府研发资助对创新绩效有间接的促进作用,其影响系数为0.405。建议政府应适当增加对制药企业的研发资助,充分发挥财政资金的引导作用;制药企业则需重视内部研发投入,建立其在创新体系中的主体地位等。     

中美政府资助罕见病与罕用药科研基金项目的比较分析

目的:探索中美政府资助罕见病与罕用药科研基金项目差异性。方法:比较分析两国罕见病和罕用药科研项目的管理规定、数量、金额、研究机构和领域五大核心内容。结果:美国出台明确科研资助的罕用药和罕见病法案;2008-2013年间,美国NIH资助37826项罕见病及罕用药科研基金项目,共计约147.3亿美元;同期,中国NSFC资助3132项此类项目,共计约12.9亿元。中美的高校为罕见病及罕用药科研项目的主要承担机构。美国罕见病及罕用药项目的研究领域相对广泛,对重点研究采取持续性资助。结论:我国的罕见病和罕用药科研项目的管理存在定义界定不明确、缺乏专项科研基金项目、管理机构和激励机制,研究经费少和研究领域窄等问题,应针对性进行改进。     

盐酸川芎嗪经腹腔注射在兔眼视网膜组织中的药代动力学

目的　测定腹腔注射盐酸川芎嗪后不同时间兔眼视网膜川芎嗪的浓度 ,计算其药动学参数 ,研究其药动学特点。方法　 4 4只家兔随机分为 11组 ,每只家兔腹腔注射盐酸川芎嗪 80mg·kg-1,在用药前 (0h)和用药后 0 2 5、0 5、0 75、1、1 5、2、3、5、8、12h取视网膜 ,采用反向高效液相色谱法 (RP HPLC)进行测定。 3P87软件拟合药动学参数。结果　腹腔注射盐酸川芎嗪后 ,其浓度在正常家兔眼视网膜呈开放型二室模型。理论值高峰浓度 (Cmax)为 1 6 3mg·g-1,达收稿日期 :2 0 0 4-0 1-3 1,修回日期 :2 0 0 4-0 2 -2 8基金资助 :广东省自然科学基金 (张清炯 0 10 765 )、国家自然科学基金(杨锦南 3 0 3 0 0 467)和广东省中医药管理局科学基金 (邓新国 10 40 0 64 )资助项目作者简介 :邓新国 ( 1961-) ,男 ,博士 ,研究方向 :眼科药物的开发、药理、药效和药代动力学研究 ;胡世兴 ( 195 2 -) ,男 ,博士 ,美国波士顿哈佛医学院眼科及免疫学博士后研究员 ,教授 ,博士生导师 ,通讯作者 ,Tel:0 2 0 873 3 0 2 89,E mail:Markhu @2 63 .net峰时间 (Tmax)为 0 32h ,半衰期T1/ 2α为 0 35h ,T1/ 2 β为 2 5 0h ,清除率 (CL)为 7 89g·h-1。实测值 15min为 (1 36± 0 16 )mg·g-1,30min达高峰为 (2 5 9± 0 19)mg·     

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     

Metabolic interaction between imipramine and carbamazepine in vivo and in vitro in rats

Summary The pharmacokinetic consequences of the combination of carbamazepine with imipramine in male Wistar rats have been investigated. It was found that a 2-week treatment with the combination resulted in the increase of the concentrations of the parent compounds and a simultaneous decrease in their metabolites in blood plasma i.e. carbamazepine inhibited imipramine demethylation in the side chain while imipramine inhibited carbamazepine 10,11-epoxidation. The velocity of imipramine 2-hydroxylation and 10,11-epoxy-carbamazepine hydration did not seem to be changed by the combination. On the basis of studies in vitro it is concluded that the observed metabolic interaction between carbamazepine and imipramine is due to the competition of the drugs for the active centre of cytochrome P 450 and to a certain qualitative alteration of the enzyme by imipramine as can be deducted from the decrease of carbamazepine binding to the cytochrome. Send offprint requests to K. J. Netter     

Buprenorphine and naloxone alone and in combination in opioid-dependent humans

Subjective, physiological and behavioral effects of subcutaneously administered hydromorphone (6 mg), naloxone (0.2 mg), buprenorphine (0.2 and 0.3 mg), and two buprenorphine-naloxone combinations (buprenorphine 0.2 mg plus naloxone 0.2 mg and buprenorphine 0.3 mg plus naloxone 0.2 mg) were assessed under double-blind conditions in six opioid-dependent volunteers. Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 120 min after drug administration. Hydromorphone decreased pupil diameter and respiration, increased blood pressure and increased scores on subjective measures indicating opioid-like effects. Buprenorphine given alone had no significant effect on any variable measured. Naloxone given alone produced opioid abstinence-like effects which were measurable on subject- and observer-rated behavioral measures and physiological measures. Buprenorphine in combination with naloxone somewhat attenuated the naloxone-precipitated withdrawal response. Overall, the naloxone-buprenorphine combinations produced effects which were qualitatively similar to the effects of naloxone alone, suggesting a low potential for abuse of the combination product by opioid-dependent individuals.Supported by a grant from Reckitt and Colman Pharmaceutical Division and USPHS Grants DA-00050 and DA-04089 from the National Institute on Drug Abuse     

Consistency in catecholamine and cortisol excretion in males and females

Data from a series of experiments performed on 24 female and 24 male subjects were used to evaluate the consistency in urinary catecholamine and cortisol excretion. Data were available from 8 laboratory situations of varying activity level and content, spaced at intervals of maximum 3 months. Correlational analyses showed that for cortisol, interindividual consistency was higher for measures obtained on the same day than for measures obtained on different days. Interindividual consistency was generally high in catecholamine and cortisol excretion during non-stressful situations in both sexes. During experimental stress, however, consistency was as high as during nonstress for males, while it was lower for females. Analysis of variance components confirmed these results and showed that in males variation due to interindividual differences was high during both baseline and experimental-stress situations, while in females it was high during baseline situations only. During experimental stress, variation for females was due primarily to interaction. It is suggested that the males showed a more generalized stress response over situations than the females.     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85–100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Strain-dependency in motor activity and in concentration and turnover of catecholamines in synchronized rats

Circadian rhythm in motor activity was studied with an Animex motimeter in six strains of rats (ACI, BH, BS, DA, LEW, TNO) synchronized by a 12 hr light: 12 hr dark cycle. ANOVA revealed significant interstrain differences in motor activity as well as in the concentration and turnover of central noradrenaline and dopamine. Strain-dependent differences were also found with regard to tyrosine hydroxylase inhibition on motor activity. However, no significant interstrain correlations were found between endogenous concentration and/or turnover rates of the catecholamines and motor activity in normal and drug-treated rats.     

Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteers

Objectives  The WHO recommends artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria. At least 15 African countries have adopted artesunate plus amodiaquine as treatment policy. As no pharmacokinetic data on this combination have been published to date, we investigated its pharmacokinetic interactions and tolerability in healthy volunteers in Africa. Methods  In a randomized, three-phase, cross-over study, amodiaquine (10 mg/kg) and artesunate (4 mg/kg) were given as single oral doses to 15 healthy volunteers. Artesunate was given to all volunteers on day 0. On day 7 they received either amodiaquine or amodiaquine plus artesunate and the alternative regimen on day 28. The pharmacokinetics of artesunate and amodiaquine and their main active metabolites dihydroartemisinin and desethylamodiaquine were compared following monotherapy and combination therapy using analysis of variance. Results  Thirteen volunteers completed the study, and pharmacokinetic parameters could be determined for twelve volunteers. When given in combination, the mean AUC was lower for dihydroartemisinin [ratio 67% (95% CI 51–88%); P = 0.008] and desethylamodiaquine [ratio 65% (95% CI 46–90%); P = 0.015] when compared with monotherapy. Adverse events of concern occurred in four volunteers (27%): grade 3 transaminitis (n = 1), neutropaenia (n = 2), and hypersensitivity (n = 1). Conclusion  The total drug exposure to both drugs was reduced significantly when they were given in combination. The clinical significance of these interactions is unclear and must be studied in malaria patients. The frequency and nature of adverse events among the healthy volunteers were of concern, and suggest laboratory monitoring would be needed in malaria patients treated with artesunate plus amodiaquine.     

Evaluation of pharmacokinetic interactions between bicyclol and co-administered drugs in rat and human liver microsomes in vitro and in rats in vivo

1. Bicyclol is a new synthetic anti-hepatitic drug and primarily metabolized by CYP3A. The aim of this study was to evaluate the pharmacokinetic interactions between bicyclol and co-administered drugs including metformin, pioglitazone, atorvastatin, fenofibrate, Cyclosporin A (CsA), and tacrolimus in rat and human liver microsomes (RLMs/HLMs) in vitro and in rats in vivo.

2. The depletion rate of bicyclol in RLMs was significantly inhibited by 44.8% and 35.5% after preincubation with pioglitazone and fenofibrate while the metabolite formation rate of bicyclol in HLMs was inhibited by 26.1% and 23.9% after preincubation and coincubation with tacrolimus, and by 20.2% after preincubation with CsA. Conversely, preincubation and coincubation with bicyclol significantly inhibited the depletion rate of pioglitazone in RLMs by 34.1% and 27.1%, respectively, and the formation rate of para- and ortho-hydroxy atorvastatin in RLMs and HLMs by 20.6–36.2%. There were no significant pharmacokinetic interactions between bicyclol and pioglitazone in rats after a single or multiple oral treatment.

3. As the selected inhibitory drug concentrations in vitro were significantly higher than those in clinical settings and the maximum inhibition rate did not exceed 50%, the clinically significant interaction between bicyclol and these co-administered drugs in humans is predicted less likely to happen.

     

Fluvastatin efficacy and tolerability in comparison and in combination with cholestyramine

The aim of this study was to investigate the new synthetic HMG-CoA reductase inhibitor, fluvastatin, for efficacy, safety and tolerability in comparison to cholestyramine. One hundred fifty one primary hypercholesterolaemic patients participated in this double-blind, parallel-group, randomized study. During the first 12 weeks of the study, fluvastatin (20 mg and 40 mg daily) was compared with cholestyramine (16 g per day). In the subsequent, 6-week part of the study, the comparative efficacy, safety and tolerability of 20 mg fluvastatin, combined with cholestyramine (4 g, 8 g, or 16 g) were assessed.Fluvastatin (40 mg) reduced LDL cholesterol by 28.0%, triglycerides by 10.5% and increased HDL cholesterol by 3.7%. Cholestyramine (16 g) reduced LDL cholesterol by 35.0%, but raised triglycerides and HDL cholesterol by 12.3% (p<0.01) and 3.7% respectively.The combination of fluvastatin 20 mg and cholesty-ramine (4 g, 8 g and 16 g) induced the following reductions in LDL cholesterol: 30.4%, 35.6% and 46.6% respectively. There was no significant change in triglycerides in either group although HDL cholesterol was raised by 4.9%, 8.3% and 7.2% respectively. One patient treated with fluvastatin and two treated with cholesty-ramine were withdrawn from the study due to elevation of liver transaminases. The most frequent subjective adverse effects in both treatment groups were mild, transient gastrointestinal complaints.Thus, fluvastatin was effective as a lipid-lowering agent; the effect was further enhanced when fluvastatin was combined with cholestyramine.     

Nicotine-induced hypophagia and hypodipsia in deprived and in hypothalamically stimulated rats

Nicotine, in doses of 0.15 and 0.45 mg/kg, induced hypophagia and hypodipsia in 20 hrs-deprived rats and elevated the threshold currents for hypothalamically induced feeding and drinking in satiated rats. These effects were blocked by pretreatment with 0.5 mg/kg mecamylamine, but not by pretreatment with 3.0 or 9.0 mg/kg hexamethonium. These results indicate a centrally-located mechanism for the hypophagic and hypodipsic effect of single injections of nicotine.