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71.
Claudia Linde Cornelia Löffler Christina Kessler U. Quast 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(4):467-474
In vascular smooth muscle, openers of ATP-dependent potassium channels (K
ATP channels), such as P1075 (N-cyano-N’-(1,1-dimethylpropyl)-N’’-3-pyridylguanidine), produce relaxation. In this study we have investigated the effects of thiol-modifying agents on the
binding of P1075 and on the 86Rb+ efflux stimulating and vasorelaxant effects of the opener in rat aortic rings. The increase in 86Rb+ efflux induced by P1075 was taken as a qualitative measure of K+ channel opening. The hydrophilic SH-group-oxidizing substance, thimerosal (1 to 100μM), abolished specific binding of [3H]-P1075 with an IC50 value of 7.6±1.2μM; at 30μM, the half time for inhibition was 38min. Two other thiol-oxidizing agents, PMB (4-hydroxy-mercuribenzoic
acid) and DTBNP (2,2’-dithio-bis(5-nitropyridine)), inhibited binding up to 86% and 44%, respectively. The disulphide bond
reducing substance, DTT (1,4-dithiothreitol, 0.1 to 1mM), reduced [3H]-P1075 binding by up to 20% and partially reversed the inhibitory effect of thimerosal. In 86Rb+ efflux experiments, thimerosal (3 to 100μM) concentration-dependently increased basal efflux but inhibited P1075-stimulated
tracer efflux with an IC50 value of 7±1μM. The inhibitory effect occurred with a half-time of approximately 8min and was essentially reversed by DTT.
In rings precontracted with noradrenaline, thimerosal inhibited the vasorelaxant effect in a noncompetitive manner, shifting
the concentration-relaxation curves to the right and reducing maximum relaxation.The data show that oxidation of thiol groups
interferes with the binding of the K
ATP channel opener, P1075; concomitantly, the 86Rb+ efflux stimulating and the vasorelaxant effects are inhibited. Reduction of disulphide bonds by DTT has only minor effects
on the action of P1075. Collectively, the results suggest that intact thiol groups are essential for the functioning of the
KATP channel in rat aorta. The different kinetics governing the inhibition of opener binding and of opener-stimulated 86Rb+ efflux suggest that the SH-groups involved in the two processes differ in their accessibility to thimerosal and/or in their
reactivity.
Received: 7 April / Accepted: 9 July 1997 相似文献
72.
Marc Ziegler Alexandre Castro-Caldas Susanna Del Signore Olivier Rascol 《Movement disorders》2003,18(4):418-425
Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on alpha2A and alpha2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: -10.0 points in the piribedil group vs. -6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients. 相似文献
73.
74.
5-羟色胺对大鼠脊髓P物质痛觉调制的影响(英文) 总被引:1,自引:0,他引:1
比较SP,5-HT与For诱发的脊髓内c-fos表达的异同,以及它们之间的相互关系,从而进一步了解SP在脊髓痛觉调制中的主要作用.方法:用免疫组织化学法和痛阈测定法.结果:发现大鼠it P物质(sP)10μg和sc5%甲醛(For)150μL诱发的脊髓c-fos表达主要在背角Ⅰ,Ⅱ,Ⅴ及Ⅵ层,同时SP使痛阈降低,For使痛级均数(PIR)升高.5-HT it 20μg引起的c-fos表达较多地分布于背角Ⅲ—Ⅳ层,并可使痛阈升高.5-HT和Fen可分别减弱和增加SP及For诱发的脊髓c-fos表达及痛反应.结论:SP在脊髓内可能主要起致痛作用,5-HT可抑制SP引起的脊髓c-fos表达,从而参与SP的痛觉调制作用. 相似文献
75.
Evidence for the presence of substance P-like immunoreactivity in the human cerebellum 总被引:1,自引:0,他引:1
M. Del Fiacco M. T. Perra M. Quartu M. D. Rosa G. Zucca M. C. Levanti 《Brain research》1988,446(1):173-177
Preliminary results on the localization of substance P-like immunoreactivity in the human cerebellum are presented. Cerebella from newborn and adult subjects were examined. While only sporadic positive fibres were detected in the adult tissue, the immunoreactive material appeared more abundant in the cerebella from newborn subjects. Varicose and non-varicose fibres and dot-like nerve terminals were present with different density in various regions. The paucity of immunoreactive perikarya suggests that most of the cerebellar substance P-like immunoreactive material has an extrinsic origin. 相似文献
76.
Nd:YAG激光对牙本质钙/磷比值的影响 总被引:1,自引:0,他引:1
朱庆萍 《临床口腔医学杂志》1998,14(3):131-132
为探讨Nd:YAG激光对牙本质矿物含量的影响,应用扫描电镜和能谱仪定点测量50个上前牙标本的根管壁(激光照射工和正常对比区)的钙、磷含量,结果表明,照射区牙本质钙/磷(Ca/P)比值高于对比区,当激光能量达15W以上时变化更为显著,提示Nd:YAG激光能提高牙本质的钙化程度。 相似文献
77.
本文采用RP-HPLC方法对紫苏油及其习用品白苏油、野苏油甘油酯进行了定性定量分析。利用HPLC分析油脂也为中药材真伪鉴别提供了一条有效途径。 相似文献
78.
目的 :通过检测 P73蛋白、P2 1蛋白在乳腺癌中的表达及其与临床病理指标的关系 ,探讨乳腺癌的生物学特性 ,分析它们在乳腺癌的发生、转移中所起的作用。方法 :应用免疫组化 S-P法检测 68例乳腺癌石蜡包埋标本中 P73、P2 1的表达情况。结果 :a.在乳腺癌 - 级与 级之间 P73蛋白阳性率分别为 1 8.75 % ( 9/48)和 60 .0 0 % ( 1 2 /2 0 ) ,差异有显著性 ( P <0 .0 5 )。随着 P73阳性表达率增高 ,乳腺癌的恶性程度增高。b.淋巴结转移组 p2 1的阳性表达率 2 3 .3 3 % ( 7/3 0 )明显低于无淋巴结转移组的阳性率 5 2 .63 % ( 2 0 /3 8) ,差异有显著性( P <0 .0 5 )。c.P73、P2 1之间无相关。结论 :P73、P2 1与乳腺癌的发生、发展有关 相似文献
79.
正规康复治疗对脑卒中患者P300的影响 总被引:5,自引:0,他引:5
目的研究正规康复治疗对脑卒中患者P300的影响,为脑卒中患者认知功能的康复提供临床依据.方法按照统一的入选条件选取2001年10月~2002年2月在本院住院的脑卒中患者60例为研究对象,随机分成康复组和对照组,康复组在脑卒中后3~7 d开始康复治疗,为期1个月.对照组未给予康复治疗,治疗前后进行P300检查.结果康复组在康复后与对照组及在康复后与康复前相比,P300的潜伏期明显缩短,波幅明显增高(P<0.01).结论正规康复治疗可以明显改善脑卒中患者的认知功能. 相似文献
80.
慢性阻塞性肺疾病前驱性呼吸衰竭患者呼吸驱动的改变 总被引:15,自引:4,他引:11
目的探讨慢性阻塞性肺疾病(COPD)和COPD前驱性呼吸衰竭(前驱呼衰)患者中枢呼吸驱动的改变;评价界定COPD前驱性呼吸衰竭的临床意义.方法试验对象为COPD前驱性呼吸衰竭、COPD尚未达前驱性呼吸衰竭的患者和健康对照者各30名.所有受试者均进行如下参数的测定:动脉血气分析;常规肺功能,主要以第1秒用力呼气容积(FEV1)占预计值的百分比(FEV1%)来评价;中枢呼吸驱动水平,以0.1 s口腔阻断压(P0.1)、校正中枢呼吸驱动(以每分通气量来校正,即P0.1/MV)和吸气阻抗P0.1/VT/Ti)等来评价.结果P0.1和P0.1/MV在COPD前驱呼衰组明显高于正常对照组和未达前驱呼衰组,P0.1/VT/Ti在COPD前驱呼衰组和未达前驱呼衰组明显高于正常对照组(P=0.002);P0.1,P0.1/MV,P0.1/VT/Ti与PaO2,FEV1%呈显著负相关(rs=-0.769,-0.495,-0.543;-0.747,-0.480,-0.526,P均<0.01);与PaCO2呈显著正相关(rs=0.270,0.312,0.369,P分别为<0.05,<0.01,<0.01).结论COPD前驱呼衰患者呼吸储备能力减低,呼吸效率下降;P0.1,P0.1/MV,P0.1/VT/Ti等参数在推断患者神经-肌力输出水平与呼吸衰竭发生阈值方面具有较大的意义.当COPD进展至前驱呼衰阶段,从血气分析、肺功能检查到呼吸驱动水平都发生了显著的改变,从而提示界定此阶段具有一定的临床意义. 相似文献