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浙江大学学报（医学版） 2008年第2期37卷 193-197页

作者：方华李昌熙王泉云刘进左云霞四川大学华西医院麻醉科四川成都610041

目的:探讨体外循环(CPB)中犬心肌能量代谢和脂质过氧化反应的变化,并用吡咯烷二硫氨基甲酸酯(PDTC)进行干预治疗。方法:将12只犬随机分为对照组(C组,n=6)和PDTC组(P组,n=6),建立CPB心肌缺血再灌注模型。P组于CPB前静脉注射PDTC 30 mg/k... 详细信息

目的:探讨体外循环(CPB)中犬心肌能量代谢和脂质过氧化反应的变化,并用吡咯烷二硫氨基甲酸酯(PDTC)进行干预治疗。方法:将12只犬随机分为对照组(C组,n=6)和PDTC组(P组,n=6),建立CPB心肌缺血再灌注模型。P组于CPB前静脉注射PDTC 30 mg/kg,C组静脉注射等量生理盐水。分别于CPB前和阻断主动脉60 min及开放主动脉60 min时,取心肌进行三磷酸腺苷(ATP)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)含量和线粒体肿胀度(MSD)检测。于CPB前和开放主动脉30 min及开放主动脉60 min时测定血液动力学指标。结果:P组在阻断主动脉60 min和开放主动脉60 min时ATP、SOD、GSH-PX含量均显著高于C组(P<0.01),而MDA和MSD均显著低于C组(P<0.01)。P组在开放主动脉30 min和开放主动脉60 min时血液动力学指标恢复迅速(P<0.01)。结论:PDTC可明显提高缺血心肌抗氧化能力,改善心肌能量代谢。

关键词：吡咯烷类/治疗应用吡咯烷二硫氨基甲酸酯抗氧化作用心肌保护体外循环

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The use of glycoprotein IIb/IIIa inhibitors in patients with coronary artery disease

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AMERICAN JOURNAL OF MEDICINE 2000年第3期109卷 224-237页

作者： Sabatine, MS Jang, IK Massachusetts Gen Hosp Div Cardiol Boston MA 02114 USA Harvard Univ Sch Med Boston MA USA

Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of acute coronary syndromes as well as in the prevention of complications after percutaneous coronary interventions. Approximately 50,000 patients with coronary artery disease have been enrolled in randomized studies of glycoprotein IIb/IIIa inhibitors. The purpose of this article is to review the pharmacology of glycoprotein IIb/IIIa inhibitors, the results of the clinical trials using these agents, and their current use in percutaneous coronary interventions and the treatment of acute coronary syndromes. (C) 2000 by Excerpta Medica, Inc.

关键词：乙酸盐类/治疗应用急性病投药口服丙氨酸/治疗应用抗体单克隆/治疗应用抗凝药/投药和剂量抗凝药/治疗应用苄脒类/治疗应用冠心病/药物疗法冠心病/治疗出血/化学诱导免疫球蛋白Fab片段/治疗应用心肌梗死/药物疗法肟类/治疗应用肽类/治疗应用哌啶类/治疗应用血小板聚集抑制剂/治疗应用血小板糖蛋白GPⅡb-Ⅲa复合物/拮抗剂和抑制剂吡咯烷类/治疗应用随机对照试验(主题) 支架综合征血小板减少/化学诱导血栓溶解疗法酪氨酸/类似物和衍生物酪氨酸/治疗应用人类

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Peripheral effects of the κ-opioid agonist EMD 61753 on pain and inflammation in rats and humans

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1999年第1期290卷 354-361页

作者： Machelska, H Pflüger, M Weber, W Piranvisseh-Völk, M Daubert, JD Dehaven, R Stein, C Free Univ Berlin Klinikum Benjamin Franklin Klin Anaesthesiol & Operative Intensivmed D-12200 Berlin Germany Johns Hopkins Univ Dept Anesthesiol & Crit Care Med Baltimore MD USA NIDA Preclin Pharmacol Lab Intramural Res Program NIH Baltimore MD USA Univ Munich Dept Anesthesiol Munich Germany Adolor Corp Malvern PA USA

The objective of the present study was to evaluate the effects of EMD 61753 (asimadoline), a K-opioid receptor agonist with restricted access to the central nervous system, on postoperative pain in patients who underwent knee surgery and on nociceptive thresholds and inflammation in rats treated with Freund's complete adjuvant. Patients treated with EMD 61753 (10 mg p.o.) tended to report an increase in pain, as evaluated by a visual analog scale and by the time to the first request for and the total amount of supplemental analgesic medication. The global tolerability of EMD 61753 was assessed as significantly inferior to that of a placebo by the investigator. In rats, the bilateral intraplantar (***.) injection of EMD 61753 (0.1-3.2 mg) resulted in dose-dependent antinociception in both inflamed and noninflamed paws, with a peak at 5 min after injection, as evaluated by the paw pressure method. However, at later time points (1 h-4 days), a significant decrease in the paw pressure threshold was observed, confirming its tendency toward a hyperalgesic action in humans. This was accompanied by an increase in paw volume and paw temperature, with a peak at 6 h after injection. EMD 61753 (1.6 mg)-induced analgesia was blocked by the peripheral opioid receptor antagonist naloxone methiodide (2.5-10 mg/kg s.c.) and by the kappa-receptor antagonist nor-binaltorphimine (0.1 mg;***.). In contrast, EMD 61753 (1.6 mg)-induced hyperalgesia and increases in paw volume and paw temperature were blocked neither by naloxone methiodide (10-40 mg/kg s.c.) nor by dizocilpine maleate (0.003-0.009 mg i,pl.), a N-methyl-D-aspartic acid receptor antagonist. These data show differentially mediated peripheral actions of EMD 61753: K-opioid receptor-induced analgesia and nonopioid, non-N-methyl-D-aspartic acid hyperalgesic and proinflammatory effects.

关键词：乙酰胺类/代谢乙酰胺类/药理学乙酰胺类/治疗应用镇痛药阿片类/代谢镇痛药阿片类/药理学镇痛药阿片类/治疗应用关节炎实验性/药物疗法关节炎实验性/病理学关节炎实验性/病理生理学关节镜检查行为动物/药物作用 CHO细胞仓鼠亚科双盲法炎症/药物疗法炎症/病理学炎症/病理生理学膝关节/外科学疼痛/药物疗法疼痛/病理生理学疼痛测定痛阈/药物作用疼痛手术后/药物疗法疼痛手术后/病理生理学吡咯烷类/代谢吡咯烷类/药理学吡咯烷类/治疗应用大鼠 Wistar 受体阿片样 κ/激动剂受体阿片样 κ/代谢成年人动物女(雌)性人类男(雄)性大鼠

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Pyrrolidine dithiocarbamate prevents I-κB degradation and reduces microvascular injury induced by lipopolysaccharide in multiple organs

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MOLECULAR PHARMACOLOGY 1999年第4期55卷 658-667页

作者： Liu, SF Ye, XB Malik, AB Univ Illinois Coll Med Dept Pharmacol Chicago IL 60612 USA

Lipopolysaccharide (LPS) is a key mediator of multiple organ injury observed in septic shock. The mechanisms responsible for LPS-induced multiple organ injury remain obscure. In the present study, we tested the hypothesis that the LPS-induced injury occurs through activation of the transcription factor, nuclear factor-kappa B (NF-kappa B). We examined the effects of inhibiting NF-kappa B activation in vivo in the rat on LPS-induced: 1) gene and protein expression of the cytokine-inducible neutrophil chemoattractant (CINC) and intercellular adhesion molecule-1 (ICAM-1);b) neutrophil influx into lungs, heart, and liver;and c) increase in microvascular permeability induced by LPS in these organs. LPS (8 mg/kg, i.v.) challenge of rats activated NF-kappa B and induced CINC and ICAM-1 mRNA and protein expression. Pretreatment of rats with pyrrolidine dithiocarbamate (50, 100, and 200 mg/kg, i.p.), an inhibitor of NF-kappa B activation, prevented LPS-induced I-kappa B alpha degradation and the resultant NF-kappa B activation and inhibited, in a dose-related manner, the LPS-induced CINC and ICAM-1 mRNA and protein expression. Pyrrolidine dithiocarbamate also markedly reduced the LPS-induced tissue myeloperoxidase activity (an indicator of tissue neutrophil retention) and the LPS-induced increase in microvascular permeability in these organs. These results demonstrate that NF-kappa B activation is an important in vivo mechanism mediating LPS-induced CINC and ICAM-1 expression, as well as neutrophil recruitment, and the subsequent organ injury. Thus, inhibition of NF-kappa B activation may be an important strategy for the treatment of sepsis-induced multiple organ injury.

关键词：抗氧化剂/治疗应用毛细血管/病理学毛细血管通透性/药物作用趋化因子 CXC 趋化因子类/生物合成趋化因子类/遗传学 DNA结合蛋白质类/代谢酶抑制生长物质/生物合成生长物质/遗传学 I-κB蛋白质类胞间黏附分子1/生物合成胞间黏附分子1/遗传学胞间信号肽类和蛋白质类脂多糖类/毒性 NF-κB/代谢中性白细胞/药物作用中性白细胞/代谢过氧化物酶/代谢吡咯烷类/治疗应用 RNA 信使/生物合成 RNA 信使/药物作用大鼠 Sprague-Dawley 休克脓毒性/病理学硫代氨基甲酸酯类/治疗应用动物男(雄)性大鼠

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Muscarinic receptor antagonists in the treatment of overactive bladder

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UROLOGY 2000年第5A期55卷 33-46页

作者： Chapple, CR Royal Hallamshire Hosp Dept Urol Sheffield S10 2JF S Yorkshire England

A wealth of clinical evidence supports the view that. muscarinic receptor antagonists are effective in the treatment of overactive bladder. However, treatment-limiting adverse effects such as dry mouth, constipation, and blurred vision have restricted the usefulness of previously available agents, such as oxybutynin. A real need therefore existed for effective and well-tolerated agents for the long-term management of the troublesome symptoms of overactive bladder. This review outlines the various approaches that have been used in attempts to overcome the tolerability problems of oxybutynin. It also describes how advances in our understanding of muscarinic receptors and bladder function has led to the potential development of either tissue- or subtype-selective antimuscarinic agents with improved tolerability. Drugs that have been developed in this way include tolterodine and darifenacin, each of which shows some bladder selectivity in animal models. Unlike darifenacin, however, the bladder selectivity of tolterodine has been confirmed by numerous clinical studies. Tolterodine's improved tolerability compared with oxybutynin, along with its equivalent therapeutic efficacy at recommended dosages, permits patients to experience the beneficial effects of long-term treatment. Tolterodine therefore represents a real alternative for the long-term management of overactive bladder. The results of ongoing clinical studies with darifenacin are awaited before it can be concluded that selective antagonism of M-3 receptors leads to improved tolerability over existing agents in the treatment of overactive bladder. Similarly, the potential improvements in tolerability associated with different dosage formulations of oxybutynin, and the clinical utility of S-oxybutynin, are yet to be conclusively demonstrated. UROLOGY 55 (Suppl 5A): 53-46, 2000. (C) 2000, Elsevier Science Inc.

关键词：二苯甲基化合物/治疗应用苯呋喃类/治疗应用临床试验(主题) 甲酚类/治疗应用扁桃酸类/治疗应用毒蕈碱拮抗剂/治疗应用苯丙醇胺吡咯烷类/治疗应用膀胱疾病/并发症膀胱疾病/药物疗法尿失禁/并发症尿失禁/药物疗法人类

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Prior peripheral arterial disease and cerebrovascular disease are independent predictors of adverse outcome in patients with acute coronary syndromes: Are we doing enough? Results from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study

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AMERICAN HEART JOURNAL 2003年第4期145卷 622-627页

作者： Cotter, G Cannon, CP McCabe, CH Michowitz, Y Kaluski, E Charlesworth, A Milo, O Bentley, J Blatt, A Krakover, R Zimlichman, R Reisin, L Marmor, A Lewis, B Vered, Z Caspi, A Braunwald, E Assaf Harofeh Med Ctr Cardiol Inst IL-70300 Zerifin Israel Brigham & Womens Hosp Boston MA 02115 USA Nottingham Clin Res Grp Nottingham England Wolfson Med Ctr Holon Israel Barzilai Govt Hosp Ashqelon Israel Rebecca Sieff Govt Hosp Safed Israel Lady Davis Med Ctr Haifa Israel Kaplan Med Ctr Rehovot Israel

Background Cerebrovascular accidents (CVAs), transient ischemic attacks (TIAs), and peripheral arterial disease (PAD) frequently coexist with coronary artery disease (CAD) and were previously reported to adversely affect the prognosis of patients with chronic CAD. Methods We examined the effect of prior CVA/TIA or PAD (extra-cardiac vascular disease [EVD]) on the outcome of 10,281 patients with acute coronary syndromes enrolled in. the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction (OPUS-TIMI) 16 trial of the oral glycoprotein Ilb/IIIa antagonist orbofiban plus aspirin versus aspirin alone. We evaluated mortality, recurrent cardiac events, and stroke and used multivariate analysis to control for differences in baseline characteristics. Results Patients with EVD were older, had more coronary risk factors, had a history of CAD, and received more intensive medical treatment at baseline. The acute event in these patients was more often unstable angina pectoris and less commonly Q-wave myocardial infarction. With coronary angiography, patients with prior EVD more often had multivessel disease. During the 10 months of follow-up, the presence of EVD was predictive of an increased hazard of death, reinfarction, recurrent ischemia, stroke, and a composite of these events. Despite the increased severity of the CAD and increased risk of events, patients with EVD were treated less frequently with beta-blockers and more frequently with calcium blockers. Despite patients with EVD having a 45% higher incidence of hypercholesterolemia, lipid-lowering agents were prescribed in a similar percentage of patients as patients without EVD. Conclusion In patients with acute coronary syndromes, the presence of prior CVA, TIA, or PAD is associated with more extensive CAD and worse outcome. These patients appear to receive less aggressive treatment, which may explain, at least in part, their worse outcome.

关键词：丙氨酸/治疗应用阿司匹林/治疗应用脑血管障碍/并发症冠心病/并发症冠心病/药物疗法双盲法药物疗法联合随访研究多元分析外周血管疾病/并发症血小板聚集抑制剂/治疗应用血小板糖蛋白GPⅡb-Ⅲa复合物/拮抗剂和抑制剂前瞻性研究吡咯烷类/治疗应用回归分析危险因素治疗结果老年人女(雌)性人类

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Increased platelet reactivity in patients given Orbofiban after an acute coronary syndrome:: An OPUS-TIMI 16 substudy

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第4期85卷 491-493页

作者： Holmes, MB Sobel, BE Cannon, CP Schneider, DJ Univ Vermont Coll Med Cardiol Unit Dept Med Burlington VT 05401 USA Brigham & Womens Hosp Cambridge MA USA Harvard Univ Sch Med Cambridge MA 02138 USA

Platelet reactivity is increased in patients with acute coronary syndromes, accounting in part for the propensity to progressive or recurrent thrombosis.1,2 Accordingly, platelet surface glycoprotein IIb-IIIa (GP IIb-IIIa) inhibitors have been used to reduce platelet aggregation and the incidence of subsequent cardiac events.3–6 The Orbofiban in Patients with Unstable coronary syndromes–Thrombolysis In Myocardial Infarction (OPUS-TIMI 16) trial was designed to determine whether orbofiban, an orally active agent of this type, was effective. Despite its promise in preliminary studies, orbofiban did not reduce the 30-day combined end point of death, myocardial infarction, or recurrent ischemia (placebo 10.7%, orbofiban 9.5%, p = NS). Furthermore, 1 of the 2 active treatment groups had an increase in death after 30 days (placebo 1.4%, orbofiban 2.3%, p <0.05).7 To clarify factors that could be responsible for the lack of efficacy, we evaluated platelet reactivity in blood samples from 15 patients enrolled in OPUS-TIMI 16.

关键词：急性病投药口服丙氨酸/投药和剂量丙氨酸/治疗应用血小板/药物作用血小板/生理学冠状动脉血栓形成/血液冠状动脉血栓形成/药物疗法纤维蛋白原/代谢血小板聚集/药物作用血小板聚集抑制剂/投药和剂量血小板聚集抑制剂/治疗应用血小板糖蛋白GPⅡb-Ⅲa复合物/拮抗剂和抑制剂吡咯烷类/投药和剂量吡咯烷类/治疗应用复发血栓溶解疗法治疗结果人类

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丁咯地尔联用速碧林治疗频发性、短暂性脑缺血发作疗效观察

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中国误诊学杂志 2006年第4期6卷 639-640页

作者：方昕陈中安武汉市商业职工医院内科湖北武汉430021

本研究旨在观察并比较丁咯地尔联用速碧林与灯盏花素联用阿斯匹林治疗频发性、短暂性脑缺血发作(TIA)的临床疗效及其副作用。[第一段]

关键词：吡咯烷类/治疗应用肝素,低分子量/治疗应用脑缺血发作,短暂性/药物疗法

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盐酸丁咯地尔联用甲钴胺治疗糖尿病周围神经病变的临床观察

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中国误诊学杂志 2008年第30期8卷 7386-7387页

作者：刘艳晓王俊宏侯卫东河南平顶山市第一人民医院内分泌科 467000

糖尿病性神经病变(DNP)是糖尿病最常见的慢性并发症之一,糖尿病周围神经病变最多见,发病机制尚未完全清楚,治疗较困难,根据对我科盐酸丁咯地尔联用甲钴胺治疗糖尿病周围神经病变情况的观察,现报道如下.

关键词：糖尿病神经病变/药物疗法周围神经系统疾病/药物疗法吡咯烷类/治疗应用维生素B12/治疗应用

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丁咯地尔治疗雷诺综合征疗效观察

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中国误诊学杂志 2010年第15期10卷 3606-3607页

作者：邱承高广西梧州市工人医院 543001

目的:观察丁咯地尔治疗雷诺综合征(RS)的临床疗效。方法:将40例RS患者随机分为两组:对照组20例给予硝苯地平缓释片和哌唑嗪片口服;治疗组20例给予盐酸丁咯地尔静脉滴注治疗。观察2组患者肢端变色、疼痛等症状及冷水实验、握拳试验、血... 详细信息

目的:观察丁咯地尔治疗雷诺综合征(RS)的临床疗效。方法:将40例RS患者随机分为两组:对照组20例给予硝苯地平缓释片和哌唑嗪片口服;治疗组20例给予盐酸丁咯地尔静脉滴注治疗。观察2组患者肢端变色、疼痛等症状及冷水实验、握拳试验、血液流变学等实验室指标治疗前后的变化。结果:治疗组总有效95.0%,对照组总有效率65.0%,两组总有效率比较差异有统计学意义(P<0.05)。两组治疗后实验室指标比较差异也有统计学意义(P<0.05)。结论:丁咯地尔治疗RS疗效肯定,不良反应少。

关键词：雷诺病/药物疗法吡咯烷类/治疗应用

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