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我国学者发现-糖尿病治疗药物或可治疗三阴性乳腺癌

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上海医药 2017年第5期38卷 65页

浙江大学医学院董辰方教授课题组发现,治疗糖尿病并发症的药物依帕司他能有效抑制乳腺癌细胞,该药物有望成为治疗致命性乳腺癌的有效靶向药物。相关论文发表于国际知名期刊《实验医学杂志》上。[第一段]

关键词：降血糖药论文学位(主题) 期刊(主题) 绕丹宁/类似物和衍生物乳腺肿瘤/病理学药用制剂院校医学浙江

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依帕司他联合前列地尔治疗2型糖尿病周围神经病变的疗效

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医学临床研究 2014年第8期31卷 1569-1571页

作者：高四红郑桃林何伟陕西省安塞县人民医院内科陕西延安717400 解放军163医院神经内科湖南长沙410003

【目的】观察依帕司他联合前列地尔治疗糖尿病周围神经病变（DPN）的临床疗效。【方法】将88例2型糖尿病（T2DM）DPN的患者随机分为对照组与观察组，各44例，两组患者均严格控制饮食、适量运动、口服降糖药或注射胰岛素控制血糖，甲钴... 详细信息

【目的】观察依帕司他联合前列地尔治疗糖尿病周围神经病变（DPN）的临床疗效。【方法】将88例2型糖尿病（T2DM）DPN的患者随机分为对照组与观察组，各44例，两组患者均严格控制饮食、适量运动、口服降糖药或注射胰岛素控制血糖，甲钴胺注射液0．5 mg肌注，每日1次。在此基础上，观察组加用依帕司他50 mg口服，每日3次；前列地尔20μg＋0．9％氯化钠注射液100 m L静脉滴注，每日1次。疗程均为2周。【结果】观察组患者自觉症状改善总有效率（97．7％）显著高于对照组（72．7％）（P＜0．05）；两组神经传导速度（NCV）均明显改善，观察组优于对照组，差异具有统计学意义（P＜0．01）。【结论】依帕司他、前列地尔及甲钴胺注射液联合治疗DPN效果显著。

关键词：绕丹宁/治疗应用绕丹宁/类似物和衍生物前列地尔/治疗应用维生素B12/治疗应用注射剂药物疗法,联合糖尿病神经病变/药物疗法治疗结果

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依帕司他与硫辛酸联合治疗糖尿病周围神经病变临床观察

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中国误诊学杂志 2007年第30期7卷 7247-7248页

作者：孙昕昳孙毓蔓杜兴旭孙琳赵殿军北华大学第一临床医院内分泌科吉林吉林132011 吉林省永吉县口前镇铁北社区卫生服务站

目的:观察依帕司他与硫辛酸联合治疗糖尿病周围神经病变的疗效,并探讨其机制。方法:116例患者分为治疗组60例,对照组56例。在理想控制血糖的基础上,治疗组给予口服依帕司他片50 mg、3次/d,连用3周;硫辛酸450mg/d静点,连用15 d;对照组患... 详细信息

目的:观察依帕司他与硫辛酸联合治疗糖尿病周围神经病变的疗效,并探讨其机制。方法:116例患者分为治疗组60例,对照组56例。在理想控制血糖的基础上,治疗组给予口服依帕司他片50 mg、3次/d,连用3周;硫辛酸450mg/d静点,连用15 d;对照组患者每天给予维生素B1100 mg及维生素B12500μg肌注,连用15 d。观察症状改善情况,并测定治疗前后正中神经和腓总神经的运动传导速度(MNCV)和感觉传导速度(SNCV),同时注意观察药物不良反应。结果:治疗组临床症状较对照组明显改善,治疗组与对照组治疗后MNCV和SNCV均较治疗前提高,但治疗组提高更明显,差异有显著性(P<0.05),且无明显不良反应。结论:依帕司他与硫辛酸联合治疗糖尿病周围神经病变,效果满意,在没有更明确治疗方法时,值得临床推广应用。

关键词：糖尿病神经病变/药物疗法周围神经系统疾病/药物疗法绕丹宁/类似物和衍生物硫辛酸/治疗应用

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依帕司他和前列地尔合用治疗糖尿病周围神经病变疗效观察

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中国误诊学杂志 2006年第21期6卷 4170-4170页

作者：陈春杰房丽梅陈茹吉林辽源矿业集团总医院内分泌科 136200

依帕司他是近年来研究的一种醛糖还原酶抑制剂,前列地尔是一种舒张血管平滑肌、改善末梢循环的药物,两药合用治疗糖尿病周围神经病变治疗效果显著。总结如下。[第一段]

关键词：绕丹宁/类似物和衍生物前列地尔/治疗应用糖尿病神经病变/药物疗法周围神经系统疾病/药物疗法

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Effects of renal sorbitol accumulation on urinary excretion of enzymes in hyperglycaemic rats

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ANNALS OF CLINICAL BIOCHEMISTRY 2001年第4期38卷 391-398页

作者： Ishii, N Ikenaga, H Ogawa, Z Aoki, Y Saruta, T Suga, T Kitasato Univ Sch Allied Hlth Sci Dept Clin Chem Sagamihara Kanagawa 2288555 Japan Keio Univ Sch Med Dept Internal Med Tokyo Japan Kanagawa Hlth Serv Assoc Clin Labs Kanagawa Japan Tokyo Univ Pharm & Life Sci Sch Pharm Dept Clin Biochem Tokyo Japan

We studied the effects of epalrestat, a specific inhibitor of aldose reductase, on renal sorbitol accumulation and the resulting urinary enzyme excretion in hyperglycaemic rats. The activities of proximal tubule-derived enzymes such as N-acetyl-beta -D-glucosaminidase (NAG), alanine aminopeptidase (AAR), gamma -glutamyltranspeptidase (GGT) and dipeptidyl aminopeptidase IV (DAPIV) in urine were determined in five groups of male Wistar rats (each n = 7): (a) 0.9% saline-loaded, (b) 10% glucose-loaded, (c) 10% glucose-loaded with epalrestat pretreatment, td) 10% mannitol-loaded and (e) 10% mannitol-loaded with epalrestat pretreatment. Epalrestat was given mixed in chow at a dose of 50 mg/kg body weight. Urinary NAG, AAP, GGT and DAPIV activities were significantly increased (P <0.005, P <0.05, P <0.01, P <0.01, respectively) by the induction of hyperglycaemia. In contrast, enzyme excretion was not increased in the mannitol- or saline-loaded groups. Pre-treatment with epalrestat completely prevented the increased urinary excretion of NAG, AAP and GGT. At the end of the infusion study, renal cortical glucose concentrations of the glucose-loaded groups with and without epalrestat pretreatment were approximately fivefold higher than those of the mannitol- or saline-loaded groups (P <0.005 each). Renal cortical sorbitol concentrations of the glucose-loaded group was also approximately twofold higher than those of the mannitol- or saline-loaded groups (P <0.01 each). However, in the group that received both glucose and epalrestat, renal cortical sorbitol concentration was not increased. These results suggest that accumulation of intracellular sorbitol leads to proximal tubular cell dysfunction and abnormal enzymuria.

关键词：乙酰氨基葡糖苷酶/尿方差分析抗原 CD13/尿抗原 CD26/血液生物学标记/尿血糖/代谢酶抑制剂/药理学肾小球滤过率/药物作用肾小球滤过率/生理学葡萄糖/投药和剂量葡萄糖/药理学高血糖症/酶学高血糖症/代谢高血糖症/尿输注静脉内肾/代谢甘露醇/药理学大鼠 Wistar 绕丹宁/类似物和衍生物绕丹宁/药理学山梨醇/代谢噻唑烷类时间因素 γ-谷氨酰转移酶/尿动物男(雄)性大鼠

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The synthesis and SAR of rhodanines as novel class C β-lactamase inhibitors

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 2000年第19期10卷 2179-2182页

作者： Grant, EB Guiadeen, D Baum, EZ Foleno, BD Jin, HY Montenegro, DA Nelson, EA Bush, K Hlasta, DJ RW Johnson Pharmaceut Res Inst Antimicrobial Agents Res Raritan NJ 08869 USA

beta-Lactam antibiotics such as the cephalosporins and penicillins have diminished clinical effectiveness due to the hydrolytic activity of diverse beta-lactamases, especially those in molecular classes A and C. A structure-activity relationship (SAR) study of a high-throughput screening lead resulted in the discovery of a potent and selective non-beta-lactam inhibitor of class C beta-lactamases. (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：药物评价临床前酶抑制剂/化学合成酶抑制剂/化学酶抑制剂/药理学分子结构哌拉西林/拮抗剂和抑制剂哌拉西林/药理学绕丹宁/类似物和衍生物绕丹宁/化学合成绕丹宁/化学绕丹宁/药理学构效关系 β内酰胺酶类/分类

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Continuous inhibition of excessive polyol pathway flux in peripheral nerves by aldose reductase inhibitor fidarestat leads to improvement of diabetic neuropathy

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JOURNAL OF DIABETES AND ITS COMPLICATIONS 1999年第3期13卷 141-150页

作者： Mizuno, K Kato, N Makino, M Suzuki, T Shindo, M Kenkyusho Co Res Dept Pharmaceut Lab Sanwa Kagaku Inabe Mie 5110406 Japan

We investigated the effects of three aldose reductase (AR) inhibitors, fidarestat, epalrestat and zenarestat, on the slowing of sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), and minimal F-wave latency prolongation in streptozotocin (STZ)-induced diabetic rats. Two weeks after STZ injection, SNCV and MNCV in the diabetic rats were significantly slower than in normal rats. Fidarestat (0.25-2 mg/kg/day), epalrestat (48 to 96 mg/kg/day) or zenarestat (10-40 mg/kg/day) was administered orally for the following 2 weeks, and SNCV, MNCV and F-wave latency were measured 3 h after final administration. Significant prolongation of minimal F-wave latency, as well as slowing of SNCV and MNCV, was found in the untreated diabetic rats 4 weeks after STZ injection. At a dose of 0.5 mg/kg/day or more fidarestat showed significant effects on these nervous dysfunctions, effects that were more potent than those shown by the other inhibitors. Furthermore, following the 2-week administration of fidarestat (1 mg/kg/day), epalrestat (48 mg/kg/day) or zenarestat (20 mg/kg/day), which began 2 weeks after STZ injection, sorbitol content in the sciatic nerve, produced by AR, a rate-limiting enzyme in the polyol pathway, was determined at 3, 8, 12, and 24 h after final administration. At each point in time, sorbitol content in the untreated diabetic rats was much higher than that in the normal control rats. Fidarestat suppressed sorbitol accumulation remarkably and continuously until 24 h after administration. On the other hand, the inhibitory effect by zenarestat declined in a time-dependent manner, and epalrestat did not decrease sorbitol content. Therefore, these results suggest that continuous inhibition of increased polyol pathway flux can improve diabetic neuropathy more potently. (C) 1999 Elsevier Science Inc.

关键词：醛还原酶/拮抗剂和抑制剂糖尿病实验性/药物疗法糖尿病实验性/代谢糖尿病神经病变/药物疗法糖尿病神经病变/代谢酶抑制剂/药理学咪唑类/治疗应用咪唑啉啶类神经传导周围神经/代谢聚合物/代谢喹唑啉类/治疗应用大鼠 Sprague-Dawley 绕丹宁/类似物和衍生物绕丹宁/治疗应用坐骨神经/代谢山梨醇/代谢噻唑烷类动物男(雄)性大鼠

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Protective effect of an aldose reductase inhibitor against bone loss in galactose-fed rats: Possible involvement of the polyol pathway in bone metabolism

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METABOLISM-CLINICAL AND EXPERIMENTAL 1999年第7期48卷 904-909页

作者： Inaba, M Terada, M Nishizawa, Y Shioi, A Ishimura, E Otani, S Morii, H Osaka City Univ Sch Med Dept Internal Med 2 Abeno Ku Osaka 545 Japan Osaka City Univ Sch Med Dept Biochem Abeno Ku Osaka 545 Japan

Many patients with diabetes mellitus show a moderate reduction in bone mass. Our recent in vitro studies showed that sustained exposure of osteoblast-like MG-63 cells to high glucose by itself impairs their functions partly via the polyol pathway. To investigate the role of hyperglycemia in the etiology of diabetic osteopenia in vivo separately from insulin deficiency, we determined whether epalrestat, an aldose reductase (AR) inhibitor (ARI), lessens the abnormalities in calcium (Ca) metabolism in galactose-fed rats. Weight gain was impaired in the rats, which was not altered by epalrestat. Galactose feeding temporarily enhanced bone resorption as reflected by increased biochemical markers for bone resorption (urinary excretion of pyridinoline [PYR] and deoxypyridinoline [DPYR]) at 1 to 3 months, which were significantly decreased by epalrestat. Epalrestat also restored the positive correlation between a bone-formation marker (serum osteocalcin [OC]) and a bone-resorption marker (urinary DPYR excretion) at 6.5 months. Histomorphometric analysis of bone performed 6.5 months after galactose feeding showed that both the bone volume and osteoblast numbers in the tibia, which were significantly suppressed by galactose feeding, were partly restored to a significant extent by the simultaneous administration of epalrestat. In summary, epalrestat partially protected against the development of osteoblast dysfunction and reduced the temporary increase in biochemical markers for bone resorption induced by galactose feeding, with a resultant increase in bone volume, suggesting that the polyol pathway may be intimately involved in the development of abnormal bone metabolism in galactose-fed rats. Copyright (C) 1999 by W.B. Saunders Company.

关键词：醛还原酶/拮抗剂和抑制剂氨基酸类/尿血糖/分析体重/药物作用骨疾病代谢性/化学诱导骨疾病代谢性/预防和控制骨和骨组织/药物作用骨和骨组织/代谢钙/尿进食/药物作用酶抑制剂/药理学半乳糖骨钙素/血液聚合物/代谢大鼠 Wistar 绕丹宁/类似物和衍生物绕丹宁/药理学噻唑烷类胫骨/药物作用胫骨/病理学动物男(雄)性大鼠

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