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Oestrogen and the cardiovascular system: the good, the bad and the puzzling   总被引:3,自引:0,他引:3  
The concept that oestrogen replacement therapy is cardioprotective has been challenged recently by the negative results of randomized clinical trials in coronary heart disease. These data have come at a time of rapid advances in our understanding of the cellular mechanisms of oestrogen. In particular, the cloning of the classical oestrogen receptor (ERalpha), the identification of a novel ER isoform (ERbeta), the availability of specific ERalpha and ERbeta knockout mice models, and the elucidation of receptor functions and signalling pathways linked to non-genomic actions of oestrogen are helping to unravel this complex biology. In this article, these advances will be discussed with particular emphasis on the regulation of nitric oxide synthesis by oestrogen. Furthermore, the puzzling issues that have emerged and the potential for development of novel and specific therapeutic approaches will be highlighted.  相似文献   

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The history of ketamine and phencyclidine from their development as potential clinical anaesthetics through drugs of abuse and animal models of schizophrenia to potential rapidly acting antidepressants is reviewed. The discovery in 1983 of the NMDA receptor antagonist property of ketamine and phencyclidine was a key step to understanding their pharmacology, including their psychotomimetic effects in man. This review describes the historical context and the course of that discovery and its expansion into other hallucinatory drugs. The relevance of these findings to modern hypotheses of schizophrenia and the implications for drug discovery are reviewed. The findings of the rapidly acting antidepressant effects of ketamine in man are discussed in relation to other glutamatergic mechanisms.Tables of Links
TARGETS
GPCRsaLigand-gated ion channelsb
κ receptorAMPA receptors
μ receptorGluN2A
ACh receptors (muscarinic)GluN2B
Cannabinoid receptorsGluN2C
D2 receptorGluN2D
Metabotrophic glutamate receptorsKainate receptors
EnzymesdNMDA receptors
CholinesterasesNicotinic ACh receptors
GAD-67
GSK-3Ion channelc
mTORHCN1
PKB (Akt)
Open in a separate window
LIGANDS
5-HTDopamineMorphine
AChEthylketocyclazocineNaloxone
AMPAHA-966NMDA
AmphetamineIfenprodilNoradrenaline
BicucullineKainatePentazocine
ChlorpromazineKetamine (CI-581)Phencyclidine
CyclazocineLevorphanolPregnenolone
D-AP5LSDQuisqualate
DextromethorphanMemantineU50488H
Dizocilpine (MK-801)
Open in a separate windowThese Tables list key protein targets and ligands in this article which are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Pawson et al., 2014) and are permanently archived in the Concise Guide to PHARMACOLOGY 2013/14a,b,c,dAlexander et al., 2013a,b,c,d,,,).  相似文献   

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医院以及医院药学的定位和服务方式转变   总被引:3,自引:0,他引:3  
本文以新一轮医药卫生体制改革的内容为切入点,分析我国现有医院与医院药学的现状,并与国外医疗体系做对比;提出了公立医院的定位问题及如何发挥医院药学在医院中的作用,转变服务方式,加强药师队伍建设等问题。  相似文献   

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Hydrogen sulfide is rapidly gaining ground as a physiological mediator of inflammation, but there is no clear consensus as to its precise role in inflammatory signaling. This article discusses the disparate anti-inflammatory ('the good') and proinflammatory ('the bad') effects of endogenous and pharmacological H(2)S in disparate animal model and cell culture systems. We also discuss 'the ugly', such as problems of using wholly specific inhibitors of enzymatic H(2)S synthesis, and the use of pharmacological donor compounds, which release H(2)S too quickly to be physiologically representative of endogenous H(2)S synthesis. Furthermore, recently developed slow-release H(2)S donors, which offer a more physiological approach to understanding the complex role of H(2)S in acute and chronic inflammation ('the promising') are discussed.  相似文献   

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Pharmaceutical research organizations can benefit from outsourcing discovery activities that are not core competencies of the organization. The core competencies for a discovery operation are the expertise and systems that give the organization an advantage over its competition. Successful outsourcing ventures result in cost reduction, increased operation efficiency and optimization of resource allocation. While there are pitfalls to outsourcing, including poor partner selection and inadequate implementation, outsourcing can be a powerful tool for enhancing drug discovery operations.  相似文献   

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骆晓莺 《中国基层医药》2010,17(21):2887-2888
目的探讨生殖道解脲支原体(UU)和沙眼衣原体(CT)与女性不孕症的关系。方法对305例不孕症患者(观察组)和130例正常女性(对照组),应用荧光定量PCR技术检测生殖道分泌物中的UU和CT,观察两组的差异。结果观察组UU、CT、UU和CT双重感染率分别为59.3%、41.0%和17.0%,均明显高于对照组(x2=89.82、44.86、19.11,均P〈0.05);原发性不孕组UU、CT感染率与继发性不孕组比较,差异均无统计学意义(均P〉0.05)。结论UU和CT的感染与女性不孕症有一定的相关性。  相似文献   

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郭秀武 《中国药事》1999,13(4):223-226
分析我国药品监督管理工作的现状,抓住机遇,迎接挑战,为把全方位的药品监督推向21世纪做好准备。  相似文献   

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目的探讨实时三维超声在膀胱癌虚拟立体模型及体积测量中的应用价值。方法对经膀胱镜活检病理确诊的29例膀胱癌患者,进行实时三维超声扫查,然后应用虚拟组织计算机辅助分析(VOCAL)技术对癌体虚拟立体模型及体积测量。结果实时三维超声不仅在膀胱癌虚拟立体模型明显优于三维图像,并且癌体体积测量十分准确。结论应用实时三维超声VOCAL技术,在膀胱癌虚拟立体模型,能够客观准确地反映癌体空间形态,并且对癌体积测量更加准确。  相似文献   

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采用光照核黄素产生氧自由基,观察后者在外周和脊髓水平对疼痛的影响。发现在外周,小鼠足跖部皮下注射LRF0.06,0.67mmol.mouse^-1有致痛作用;脊髓水平,小鼠鞘内注射LRF0.106-0.665nmol.mouse^-1有致痛敏作用;进一步研究发现OFR的脊髓痛敏与Ca^2+有密切关系,用维拉帕米,尼莫地平,EGTA可拮抗OFR的痛敏作用。  相似文献   

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