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31.
F Moureau J Wouters DP Vercauteren S Collin G Evrard F Durant F Ducrey JJ Koenig FX Jarreau 《European journal of medicinal chemistry》1992,27(9)
Toloxatone is a reversible MAOA-inhibitor, marketed as antidepressant (Humoryl®), with an original chemical structure. It differs from first generation irreversible MAOIs, known to induce covalent bonds with the enzyme active site. In order to understand the mechanism of the reversible inactivation of the MAO, as a first step, a detailed structural and electronic analysis was undertaken. An X-ray diffraction-crystallographic study showed that toloxatone is a planar molecule and brought to light hydrogen bonds and π-π interactions. MO calculations confirmed the planar structure as energetically favoured. Electronic analysis demonstrated a delocalization of both ring systems. The combined results give evidence for the potential of toloxatone to participate in reversible, long distance interactions with an appropriate partner. 相似文献
32.
妊娠末期催产素刺激子宫蜕膜细胞产生与分娩有关的前列腺素,但其作用方式仍未知。本实验分离妊娠19d大鼠蜕膜细胞,测定了催产素作用后蜕膜细胞内游离钙的变化,结果加入0.001~1μmol·L-1催产素后,蜕膜细胞内[Ca2+]i出现瞬息增加,其峰值与催产素浓度呈剂量依赖关系,且此作用有自身钝化现象。说明催产素可能激活妊娠末期大鼠蜕膜细胞内的肌醇磷酯蛋白激酶C系统。给妊娠末期大鼠ip硫酸去氢表雄酮钠盐后分离的蜕膜细胞,催产素作用引起[Ca2+]i瞬息增加峰值较对照升高。 相似文献
33.
Frazier EP Mathy MJ Peters SL Michel MC 《The Journal of pharmacology and experimental therapeutics》2005,313(1):260-267
Cyclic AMP is the prototypical second messenger of beta-adrenergic receptors, but recent findings have questioned its role in mediating smooth muscle relaxation upon beta-adrenergic receptor stimulation. We have investigated the signaling mechanisms underlying beta-adrenergic receptor-mediated relaxation of rat urinary bladder. Concentration-response curves for isoproterenol-induced bladder relaxation were generated in the presence or absence of inhibitors, with concomitant experiments using passive tension and KCl-induced precontraction. The adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536; 1 microM), the protein kinase A inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7; 10 microM), N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89; 1 microM), and Rp-adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS; 30 microM), and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 3 microM) produced only minor if any inhibition of relaxation against passive tension or KCl-induced precontraction. Among various potassium channel inhibitors, BaCl2 (10 microM), tetraethylammonium (3 microM), apamin (300 nM), and glibenclamide (10 microM) did not inhibit isoproterenol-induced relaxation. Some inhibition of the isoproterenol effects against KCl-induced tone but not against passive tension was seen with inhibitors of calcium-dependent potassium channels such as charybdotoxin and iberiotoxin (30 nM each). A combination of SQ 22,536 and ODQ significantly inhibited relaxation against passive tension by about half, but not that against KCl-induced tone. Moreover, the combination failed to enhance inhibition by charybdotoxin against KCl-induced tone. We conclude that cAMP and cGMP each play a minor role in beta-adrenergic receptor-mediated relaxation against passive tension, and calcium-dependent potassium channels play a minor role against active tension. 相似文献
34.
目的:一氧化氮在维持机体多个系统的生理功能中起重要作用,许多慢性疾病可造成一氧化氮产生减少,此时一氧化氮供体是一种必要的补充。观察一氧化氮外源性供体L-arginine对体外培养破骨细胞增殖及骨吸收功能的影响。方法:实验于2005-06/2006-05在四川大学华西医院生物治疗国家重点实验室干细胞与组织工程研究室完成。选择出生1d的清洁级SD大鼠乳鼠,采用骨髓诱导法体外培养破骨细胞,培养液内分别加入0.3,0.6,1.0g/L不同浓度的L-arginine,并以等体积三蒸水作为对照。培养7d后,以抗酒石酸酸性磷酸酶染色观察破骨细胞数目、形态,MIAS-2000图像分析仪检测骨片上骨吸收陷窝的数目和面积,并用扫描电镜观察不同浓度L-arginine对骨吸收陷窝的影响。结果:①破骨细胞的一般形态:破骨细胞较其他细胞大,形态不规则,呈油煎蛋形、长条形、腊肠形或漏斗形等,细胞内可见几个至几十个核不等。抗酒石酸酸性磷酸酶染色酶活性部分酒红色,颗粒状。②抗酒石酸酸性磷酸酶阳性细胞数:各组破骨细胞数目随着L-arginine浓度增加而减少(P<0.05)。③骨吸收陷窝的面积和数目:骨片培养7d,吸收陷窝计数的结果显示,0.3g/L以上浓度L-arginine对破骨细胞吸收功能均有明显抑制作用,并呈剂量相关性。0.3g/LL-arginine组陷窝面积为对照组的91%(P<0.05),0.6g/LL-arginine组为对照组的80%(P<0.05),1.0g/LL-arginine组为对照组的69%(P<0.01)。结论:采用骨髓诱导法培养的破骨细胞数量多、纯度高,且具有明显的骨吸收功能。L-arginine抑制破骨细胞增殖,抑制破骨细胞骨吸收功能,并呈剂量相关性。 相似文献
35.
Two monoclonal antibodies (anti-3-3 and anti-3-40) were produced, which identify two new leukemia-associated antigens. Both antibodies reacted with most cell lines derived from patients with T lymphoblastic leukemia (T-ALL), but were not detected on suspensions of normal hematopoietic cells (including thymocytes) by cytotoxicity, absorption, or indirect immunofluorescence assays. Analysis of fresh leukemic cells indicated that anti-3-3 only reacted with T-ALL cells, while anti-3-40 also reacted with some non-T, non-B ALL cells and a few acute myelocytic leukemia (AML) cells. The 3-40 antigen was also found histopathologically in frozen sections of several normal tissues, including the epithelial cells and a few lymphoid cells of the thymus, and some malignant tissues. The 3-3 antigen was not found in any tissue studied. A "double absorption"assay provided additional serologic evidence that the two antibodies identify different antigenic determinants. Biochemical analysis indicated that the molecules immunoprecipitated by anti-3-3 and anti-3-40 have molecular weights of 35,000-40,000 daltons. This study demonstrated that the 3-3 and 3-40 antigens are markers for human T-ALL and can be used along with the normal T-lymphocyte antigen, 3A1, to discriminate T-ALL from cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia (ATL), and T-cell chronic lymphocytic leukemia (T-CLL). 相似文献
36.
Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis 总被引:10,自引:0,他引:10 下载免费PDF全文
Leung SY Chen X Chu KM Yuen ST Mathy J Ji J Chan AS Li R Law S Troyanskaya OG Tu IP Wong J So S Botstein D Brown PO 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(25):16203-16208
We analyzed gene expression patterns in human gastric cancers by using cDNA microarrays representing approximately equal 30,300 genes. Expression of PLA2G2A, a gene previously implicated as a modifier of the Apc(Min/+) (multiple intestinal neoplasia 1) mutant phenotype in the mouse, was significantly correlated with patient survival. We confirmed this observation in an independent set of patient samples by using quantitative RT-PCR. Beyond its potential diagnostic and prognostic significance, this result suggests the intriguing possibility that the activity of PLA2G2A may suppress progression or metastasis of human gastric cancer. 相似文献
38.
口内路径下颌骨升枝矢状劈开截骨术治疗下颌前突畸形 总被引:8,自引:1,他引:7
归来 《口腔颌面外科杂志》1997,7(2):84-87
下颌骨升枝矢状劈开术是目前世界上使用最普遍的矫正下颌骨畸形的手术方法之一。作者采用口内入路下颌骨畸形的手术方法之一。作者采用口内入路下颌骨升枝矢状劈开截骨术治疗下颌骨前突182例,其中真性下颌前突143例,假性下颌前突39例。年龄在15~58岁之间,平均24岁。随访6个月~9年。除9例术后畸形复发需再次矫正以外均获满意效果。本文介绍了口内入路下颌骨升枝矢状截骨术的手术过程及注意事项,并着重讨论了其优缺点,可能出现的并发症及处理方法 相似文献
39.
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