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排序方式: 共有170条查询结果,搜索用时 296 毫秒
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Rats exposed to a footshock show conditional fear when reexposed to the shock context. Immediate presentation of shock after placement in the context significantly reduces this fear. Preexposure to the context in the absence of shock, coupled with a minimum preshock interval during training, overcomes this immediate shock deficit. Because rats learn about the context during preexposure and express that learning after being reinforced, the context preexposure effect is an aversive analogue of latent learning. The authors examined the effect of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphovalerate (APV) on the facilitatory effect of context preexposure. Rats were preexposed to a chamber after APV administration. The next day they were placed in the same chamber without drug and received shock 35 s later. APV blocked the facilitatory effect of preexposure. Therefore NMDA receptors are important for contextual latent learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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Muhammad Nabeel Ghayur Anwarul Hassan Gilani 《European Food Research and Technology》2007,224(4):477-481
In this study, we describe the tracheal-relaxant and tocolytic activities of the methanol (ME) and aqueous (AQ) crude extracts
of ginger (rhizome of Zingiber officinale) in an attempt to rationalize its traditional use in disorders of airways and uterine hyperactivity. Both of the ginger extracts
dose-dependently relaxed K+ (80 mM) and carbachol (CCh, 1 μM)-induced contractions with more potency against K+, similar to that elicited by verapamil, a Ca2+ channel blocker. In isolated uterine preparations, the extracts suppressed the K+-induced contractions with respective EC50 values of 0.03 mg/ml (0.02–0.05, 95% CI) and 0.05 mg/ml (0.04–0.06). Activity-directed fractionation of AQ yielded an organic
and an aqueous fraction with the activities concentrated in the former. Both the crude extracts were found safe in mice up
to the oral dose of 5 g/kg when tested for acute toxicity for 24 h. The study shows that ginger possesses tracheal and uterine
smooth muscle relaxant activity, possibility mediated via Ca2+ channel blockade, justifying its use in disorders such as asthma, cough as well as in dysmenorrhoea and uterine and menstrual
spasms and congestion. 相似文献
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Andreas Hugerth Magnus Brisander Ulla Wrange Mikael Kritikos Björn Norrlind Marianne Svensson 《Drug development and industrial pharmacy》2013,39(2):185-196
ABSTRACTThe physicochemical properties of 1-benzenesulfonyl-4-(piperazin-1-yl)-indole hydrochloride, a novel 5-HT6 receptor antagonist for the treatment of obesity were characterized. Two solid state forms were identified at ambient conditions (23°C): an anhydrate form (1) and a hydrate form (2), with 1.5 moles of H2O. The latter easily dehydrates and rehydrates without affecting the crystal morphology. Investigations of the propensity for interconversion between the two forms reveal that a) conversion of 2→1 takes place above 145°C and that b) conversion of 1→2 only occurs after crystallization from supersaturated aqueous solutions at a water activity ≥0.94 or in the presence of comparable amounts of crystals of 2 in water at ambient conditions. However, in an equimolar suspension of 1 and 2 at 37°C no phase transformation was observed. Thus, the difference in chemical potential between the two forms is small. Form 1 was shown to have overall favorable solid state properties and, hence, considered the preferred form for continued pharmaceutical development. The characterization was performed by means of light microscopy, scanning electron microscopy, powder X-ray diffraction, FTIR/NIR-spectroscopy, differential scanning calorimetry, hot stage microscopy, thermogravimetry, dynamic vapor sorption, Karl Fischer water content determination, phase stability studies of suspensions, solubility, and intrinsic dissolution rate measurements. 相似文献
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Mallory Batty Rachel Pugh Ilampirai Rathinam Joshua Simmonds Edwin Walker Amanda Forbes Shailendra Anoopkumar-Dukie Catherine M. McDermott Briohny Spencer David Christie Russ Chess-Williams 《International journal of molecular sciences》2016,17(8)
This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers. 相似文献
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目的:探讨腺苷A2A受体拮抗剂对实验性自身免疫性脑脊髓炎(EAE)的治疗作用及其对中枢炎症性小胶质细胞形态和功能的影响。方法:MOG35-55免疫诱导建立EAE模型,EAE小鼠出现神经功能缺损症状后开始腹腔注射腺苷A2AR拮抗剂至发病后第10天。ELISA法检测中枢神经系统内IFN-γ、IL-17、TGF-β、IL-10的表达情况,免疫荧光双重染色法检测小胶质细胞内M1型细胞标志物诱导型一氧化氮合酶(iNOS)和M2型细胞标志物精氨酸酶I(ArgI)的合成情况。离体培养BV-2小胶质细胞,LPS诱导的小胶质细胞炎症反应,并予A2AR拮抗剂干预,Real-time PCR和ELISA法检测M1型和M2型细胞相关的细胞因子RNA表达水平和分泌水平。Western Blot法检测各组小胶质细胞内M1型和M2型细胞标志物的表达量。结果:腺苷A2AR拮抗剂能有效缓解发病后EAE小鼠的神经功能缺损症状,降低IFN-γ的分泌水平,使M1型细胞相关的iNOS合成减少,M2型细胞相关的ArgI合成增多。腺苷A2AR拮抗剂能减少LPS刺激后BV-2小胶质细胞M1型细胞相关的细胞因子IL-1β的mRNA表达量和分泌量,对M2型细胞相关的细胞因子及蛋白无显著影响。结论:腺苷A2AR拮抗剂对发病后的EAE小鼠有肯定的治疗作用,其机制可能与改变中枢炎症过程中小胶质细胞的表型(M1/M2转换)改变(形态和功能)有关。 相似文献
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张银 《化学工业与工程技术》2014,(3):59-61
对咪达那新的合成方法进行了归纳和比较,重点介绍了关键中间体4-(2-甲基-1-咪唑基)-2,2-二苯基丁腈的合成及由关键中间体合成咪达那新的研究进展,为咪达那新的进一步研究及工业化生产提供参考。 相似文献
10.
Interplay between Endothelin and Erythropoietin in Astroglia: The Role in Protection against Hypoxia
Richard Sch?fer Lars Mueller Reinhild Buecheler Barbara Proksch Matthias Schwab Christoph H. Gleiter Lusine Danielyan 《International journal of molecular sciences》2014,15(2):2858-2875
We show that, under in vitro conditions, the vulnerability of astroglia to hypoxia is reflected by alterations in endothelin (ET)-1 release and capacity of erythropoietin (EPO) to regulate ET-1 levels. Exposure of cells to 24 h hypoxia did not induce changes in ET-1 release, while 48–72 h hypoxia resulted in increase of ET-1 release from astrocytes that could be abolished by EPO. The endothelin receptor type A (ETA) antagonist BQ123 increased extracellular levels of ET-1 in human fetal astroglial cell line (SV-FHAS). The survival and proliferation of rat primary astrocytes, neural precursors, and neurons upon hypoxic conditions were increased upon administration of BQ123. Hypoxic injury and aging affected the interaction between the EPO and ET systems. Under hypoxia EPO decreased ET-1 release from astrocytes, while ETA receptor blockade enhanced the expression of EPO mRNA and EPO receptor in culture-aged rat astroglia. The blockade of ETA receptor can increase the availability of ET-1 to the ETB receptor and can potentiate the neuroprotective effects of EPO. Thus, the new therapeutic use of combined administration of EPO and ETA receptor antagonists during hypoxia-associated neurodegenerative disorders of the central nervous system (CNS) can be suggested. 相似文献