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中国医师杂志 2018年第10期20卷 1546-1548页

作者：洪波戴茹萍戴拥黎洪宇湖南省岳阳市中医医院麻醉科 414000 中南大学湘雅二医院麻醉科长沙410011

目的探讨分析2型糖尿病及七氟烷对罗库溴铵肌肉松弛效应的影响。方法选择在本院择期行中下腹部手术患者120例,其中80例2型糖尿病患者随机分为A组和B组,每组40例,其余40例非2型糖尿病患者作为C组。各组患者均于诱导入睡后经静脉推注罗库... 详细信息

目的探讨分析2型糖尿病及七氟烷对罗库溴铵肌肉松弛效应的影响。方法选择在本院择期行中下腹部手术患者120例,其中80例2型糖尿病患者随机分为A组和B组,每组40例,其余40例非2型糖尿病患者作为C组。各组患者均于诱导入睡后经静脉推注罗库溴铵,C组和A组患者麻醉维持方式均选用异丙酚静脉麻醉,而B组患者麻醉维持方式使用七氟烷吸入麻醉。以成串刺激检测患者神经肌肉阻滞深度,记录各组患者罗库溴铵松肌作用相关指标。结果三组患者罗库溴铵肌松作用起效时间差异无统计学意义(P> 0. 05),但A组、B组患者恢复时间、恢复指数较C组明显延长(P <0. 05),且B组患者恢复时间、恢复指数较A组延长(P <0. 05)。A组、B组患者T1、T2、T3、T4恢复时间较C组明显延长(P <0. 05),且B组患者T1、T2、T3、T4恢复时间较A组延长(P <0. 05)。结论 2型糖尿病患者应用罗库溴铵可导致肌松效应恢复时间延迟,且同时运用吸入麻醉药物七氟烷可进一步延长其肌松效应恢复时间,对于2型糖尿病使用七氟烷吸入麻醉需要考虑减少罗库溴铵用量或者相应延长肌松药追加间隔时间。

关键词：糖尿病,2型/病理生理学甲醚类/药理学雄甾烷醇类/药理学肌松弛

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不同浓度右美托咪定对罗库溴铵肌松效应的影响

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中国医师杂志 2014年第10期16卷 1346-1348页

作者：冯娅妮朴春梅孙艳红马虹中国医科大学附属第一医院麻醉科沈阳110001

目的观察不同浓度右美托咪定对罗库溴铵肌松起效时间及临床时效的影响.方法择期全麻下行乳腺癌改良性根治术患者60例,年龄26～55岁,随机分为四组,每组15例.A组（对照组）：麻醉诱导前10 min内匀速输注生理盐水（NS）0.25 ml/kg;B、C、... 详细信息

目的观察不同浓度右美托咪定对罗库溴铵肌松起效时间及临床时效的影响.方法择期全麻下行乳腺癌改良性根治术患者60例,年龄26～55岁,随机分为四组,每组15例.A组（对照组）：麻醉诱导前10 min内匀速输注生理盐水（NS）0.25 ml/kg;B、C、D组分别以右美托咪定初始剂量0.3、0.6、1.0 μg/kg麻醉诱导前10 min内匀速输注完,麻醉期间以0.3、0.6、1.0 μg/（g·h）持续泵注至手术结束.患者入室后均在多功能生命体征监测仪下监测血压（BP）、心率（HR）、血氧饱和度（SpO2）、心电图（ECG）、气管插管后监测呼气末二氧化碳（EtCO2）,记录To和T25的时间及血流动力学的变化.结果 To时间各组差异无统计学意义（P＞0.05）,但C组和D组中T25时间[（48 ±6） min和（51 ±6）min]与A组[（40±6）min]比较差异有统计学意义（P＜0.05）.B、C、D组用不同浓度的右美托咪定后与A组相比,C和D组给药后5 min血压明显下降[（88.76 ±7.06） mmHg,（87.89±6.95） mmHg,P＜0.05],B组和C组诱导前心率[（60.80±7.11）次/min,（63.31 ±5.78）次/min]与A组比较明显下降（P＜0.05）,D组心率在给药后5 min、诱导前及给药后30 min明显下降[（66.40±9.49）次/min,（60.52 ±7.45）次/min,（61.32±7.11）次/min,P＜0.05].结论不同浓度右美托咪定对罗库溴铵的起效时间没有影响,但右美托咪定增加到一定浓度时能够增强罗库溴铵的临床时效.不同浓度右美托咪对围手术期的血压及心率有影响.

关键词：右美托咪啶/投药和剂量右美托咪啶/药理学肌松弛/药物作用雄甾烷醇类/药理学神经肌肉阻滞

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17β-O-aminoalkyloximes of 5β-androstane-3β,14β-diol with digitalis-like activity:: Synthesis, cardiotonic activity, structure-activity relationships, and molecular modeling of the Na⁺,K⁺-ATPase receptor

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JOURNAL OF MEDICINAL CHEMISTRY 2000年第12期43卷 2332-2349页

作者： Cerri, A Almirante, N Barassi, P Benicchio, A Fedrizzi, G Ferrari, P Micheletti, R Quadri, L Ragg, E Rossi, R Santagostino, M Schiavone, A Serra, F Zappavigna, MP Melloni, P Prassis Ist Ric Sigma Tau Dept Med Chem I-20019 Settimo Milanese MI Italy Prassis Ist Ric Sigma Tau Dept Cardiovasc Pharmacol I-20019 Settimo Milanese MI Italy Univ Milan Fac Agr Chem Sect Dept Agr & Food Mol Sci I-20133 Milan Italy

A series of digitalis-like compounds with a 17-aminoalkoxyiminoaIkyl or -alkenyl substituent was synthesized and evaluated for inhibition of Na+,K+-ATPase and for inotropic activity. The highest inhibition was found with compounds having the substituent in configuration 17 beta and the amino group at a distance of 6 or 7 bonds from C(17) of the digitoxigenin skeleton. The presence of the oxime function strengthens the interaction with the receptor, more if alpha,beta-unsaturated, thus mimicking the electronic situation of the unsaturated lactone in natural digitalis compounds. The most active compounds showed Na+,K+-ATPase inhibitory potencies (IC50) 17-25 times higher than the standards digitoxigenin and digoxin and 3-11 times higher inotropic potencies (EC50) in isolated guinea pig left atria. These features are supported by a molecular model suggesting the possible interactions of the groups described above with particular amino acid residues in the H1-H2 domains of Na+,K+-ATPase. Some interactions are the classical ones already described in the literature;a new, very strong interaction of the basic group with the Cys138 was found and adds new possibilities to design compounds interacting with this region of the receptor. The most interesting compounds were also studied in vivo in the anesthetized guinea pig for evaluating their inotropic effect versus the lethal dose. Compounds 9 and 12 showed a slightly higher safety ratio than digoxin and deserve further evaluation.

关键词：雄甾烷类/化学合成雄甾烷类/化学雄甾烷类/药理学雄甾烷醇类/化学合成雄甾烷醇类/化学雄甾烷醇类/药理学结合部位强心药/化学合成强心药/化学强心药/药理学洋地黄糖甙类/药理学酶抑制剂/化学合成酶抑制剂/化学酶抑制剂/药理学心房/药物作用肾/酶学模型分子心肌收缩/药物作用哇巴因/化学哇巴因/代谢肟类/化学合成肟类/化学肟类/药理学钠钾交换ATP酶/拮抗剂和抑制剂钠钾交换ATP酶/化学钠钾交换ATP酶/代谢构效关系动物狗豚鼠男(雄)性

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The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR

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MOLECULAR AND CELLULAR BIOLOGY 2000年第9期20卷 2951-2958页

作者： Tzameli, I Pissios, P Schuetz, EG Moore, DD Baylor Coll Med Dept Mol & Cellular Biol 1 Baylor Plaza Houston TX 77030 USA St Jude Childrens Res Hosp Dept Pharmaceut Sci Memphis TN 38105 USA

A wide range of xenobiotic compounds are metabolized by cytochrome P450 (CYP) enzymes, and the genes that encode these enzymes are often induced in the presence of such compounds. Here, we show that the nuclear receptor CAR can recognize response elements present in the promoters of xenobiotic-responsive CYP genes, as well as other novel sites. CAR has previously been shown to be an apparently constitutive transactivator, and this constitutive activity is inhibited by androstanes acting as inverse agonists. As expected, the ability of CAR to transactivate the CYP promoter elements is blocked by the inhibitory inverse agonists. However, CAR transactivation is increased in the presence of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), the most potent known member of the phenobarbital-like class of CYP-inducing agents. Three independent lines of evidence demonstrate that TCPOBOP is an agonist ligand for CAR. The first is that TCPOBOP acts in a dose-dependent manner as a direct agonist to compete with the inhibitory effect of the inverse agonists. The second is that TCPOBOP acts directly to stimulate coactivator interaction with the CAR ligand binding domain, both in vitro and in vivo. The third is that mutations designed to block ligand binding block not only the inhibitory effect of the androstanes but also the stimulatory effect of TCPOBOP. Importantly, these mutations do not block the apparently constitutive transactivation by CAR, suggesting that this activity is truly ligand independent. Both its ability to target CYP genes and its activation by TCPOBOP demonstrate that CAR is a novel xenobiotic receptor that may contribute to the metabolic response to such compounds.

关键词：氨基酸序列雄甾烷醇类/化学雄甾烷醇类/药理学结合部位印迹法蛋白质细胞系剂量效应关系药物谷胱甘肽转移酶/代谢分子序列数据诱变质粒蛋白质结构三级吡啶类/化学吡啶类/代谢受体胞质和核/激动剂受体胞质和核/遗传学受体胞质和核/代谢序列同源性氨基酸反式激活因子类/激动剂反式激活因子类/遗传学反式激活因子类/代谢转录因子转染动物人类小鼠

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The peroxisome proliferator response element of the gene encoding the peroxisomal β-oxidation enzyme enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase is a target for constitutive androstane receptor β/9-cis-retinoic acid receptor-mediated transactivation

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第6期275卷 4345-4350页

作者： Kassam, A Winrow, CJ Fernandez-Rachubinski, F Capone, JP Rachubinski, RA Univ Alberta Dept Cell Biol Edmonton AB T6G 2H7 Canada Univ Alberta Dept Biochem Edmonton AB T6G 2H7 Canada McMaster Univ Dept Biochem Hamilton ON L8N 3Z5 Canada

The genes encoding the first two enzymes of the peroxisomal beta-oxidation pathway, acyl-CoA oxidase (AOx) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD), contain upstream cis-acting regulatory regions termed peroxisome proliferator response elements (PPRE), Transcription of these genes is mediated through the binding of peroxisome proliferator-activated receptor or (PPAR alpha), which binds to a PPRE as a heterodimer with the 9-cis-retinoic acid receptor (RXR alpha). Here we demonstrate that the HD-PPRE is also a target for the constitutive androstane receptor beta (CAR beta) In vitro binding analysis showed that CAR beta bound the HD-PPRE, but not the AOx-PPRE, as a heterodimer with RXR alpha, Binding of CAR beta/RXR alpha to the HD-PPRE occurred via determinants that overlap partially with those required for PPAR alpha/RXR alpha binding. In vivo, CAR beta/RXR alpha activated transcription from an HD-PPRE luciferase reporter construct, Interestingly, CAR beta was shown to also modulate PPAR alpha/RXR alpha-mediated transactivation in a response element-specific manner. In the presence of the peroxisome proliferator, Wy-14,643, CAR beta had no effect on PPAR alpha/RXR alpha-mediated transactivation from the HD-PPRE but antagonized transactivation from the AOx-PPRE in both the presence and the absence of proliferator, Our results illustrate that transcription of the AOx and HD genes is differentially regulated by CAR beta and that the HD gene is a specific target for regulation by CAR beta, Overall, this study proposes a novel role for CAR beta in the regulation of peroxisomal beta-oxidation.

关键词：酰基CoA氧化酶雄甾烷醇类/药理学结合竞争性细胞系 DNA结合蛋白质类/遗传学二聚作用烯酰CoA水合酶/遗传学基因表达调控酶学氧化还原酶类/遗传学过氧化酶体激增剂/药理学过氧化物酶体类/酶学过氧化物酶体类/遗传学嘧啶类/药理学受体胞质和核/遗传学受体维甲酸/代谢调控序列核酸/遗传学维甲类X受体转录因子/遗传学转录因子/代谢转录激活/遗传学动物人类大鼠

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sgk is an aldosterone-induced kinase in the renal collecting duct -: Effects on epithelial Na⁺ channels

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JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第24期274卷 16973-16978页

作者： Náray-Fejes-Tóth, A Canessa, C Cleaveland, ES Aldrich, G Fejes-Tóth, G Dartmouth Med Sch Dept Physiol Lebanon NH 03756 USA Yale Univ Sch Med Dept Cellular & Mol Physiol New Haven CT 06520 USA

The early phase of the stimulatory effect of aldosterone on sodium reabsorption in renal epithelia is thought to involve activation of apical sodium channels. However, the genes initiating this effect are unknown. We used a combination of polymerase chain reaction-based subtractive hybridization and differential display techniques to identify aldosterone-regulated immediate early genes in renal mineralocorticoid target cells. We report here that aldosterone rapidly increases mRNA levels of a putative Ser/Thr kinase, sgk (or serum- and glucocorticoid-regulated kinase), in its native target cells, i.e. in cortical collecting duct cells. The effect occurs within 30 min of the addition of aldosterone, is mediated through mineralocorticoid receptors, and does not require de novo protein synthesis. The full-length sequences of rabbit and mouse sgk cDNAs were determined. Both cDNAs show significant homology to rat and human sgk (88-94% at the nucleotide level, and 96-99% at the amino acid level). Coexpression of the mouse sgk in Xenopus oocytes with the three subunits of the epithelial Na+ channel results in a significantly enhanced Na+ current. These results suggest that sgk is an immediate early aldosterone-induced gene, and this protein kinase plays an important role in the early phase of aldosterone-stimulated Na+ transport.

关键词：醛固酮/生物合成醛固酮/药理学阿米洛利/药理学氨基酸序列雄甾烷醇类/药理学导电性酶诱导即早蛋白质类肾小管集合/药物作用肾小管集合/酶学分子序列数据核蛋白质类蛋白质丝氨酸苏氨酸激酶/生物合成蛋白质丝氨酸苏氨酸激酶/遗传学 RNA 信使/生物合成受体盐皮质激素/生物合成重组蛋白质类/代谢序列同源性氨基酸动物兔

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Effect of rocuronium compared with succinylcholine on IOP

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BRITISH JOURNAL OF ANAESTHESIA 1999年第5期83卷 823-824页

作者： Lim, K Smith, AF Royal Lancaster Infirm Lancaster England

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