NEW PHARMACOLOGY ASPECTS RELATED TO CARBONIC ANHYDRASE

与碳酸酐酶相关的新药理学方面

• 批准号: 3336805
• 负责人: THOMAS H MAREN
• 金额: $ 10.77万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336805
• 关键词: acetazolamide; acid base balance; bicarbonates; brain cell; buffers; carbon dioxide; carbon dioxide tension; carbonate dehydratase; carbonic anhydrase inhibitors; cell membrane; drug design /synthesis /production; drug metabolism; egg /ovum; electrofocusing; endolymph; ion transport; ions; isozymes; mitochondria; myocardium; protonation; saltwater environment; secretion; sodium; striated muscles; sulfonamides; uterus

A five-fold program has been developed in which the central theme is the enzyme carbonic anhydrase (C.A.), its chemistry, inhibition, and role in certain organ systems, presently unknown. The continuity between biochemical and physiological events is stressed. We plan to study the following: I. The role of carbonic anhydrase in muscle, uterus, ova, and secretion of endolymph. This introduces also fundamental questions about the physiology of these organs. Particularly, in muscle we shall study CO2 output after inhibition of the enzyme; in uterus the implantation evironment; in ova the dispersion of the corona radiata; in endolymph the rate and character of secretion. II. We shall study the role of CO2 in neutral secretions (NaCl) and whether there can be renal H+ output independent of the CO2 system. III. New sulfonamide inhibitors combining lipid and water solubility will be developed. Studies of drug-enzyme kinetics will be pursued, with attention ot "uncompetitive" inhibition, and differences between the three C.A. isozymes. IV. We wish to characterize mitochondrial C.A., and also the enzyme in brain myelin, with respect to Kcat, Km, and susceptibility to inhibition by the sulfonamides. V. We plan to study gas exchange and acid-base balance in sub-order of Amphibia, the plethodonts, which lack both lungs and gills, and respire entirely through the skin. They are also the only adult vertebrates that lack red cell C.A.

已经制定了一个五重计划，其中的中心主题是 碳酸氢酶(C.A.)的化学、抑制及其在体内的作用 某些器官系统，目前尚不清楚。两者之间的连贯性 强调生化和生理事件。我们计划研究 以下内容：I.碳酸酐酶在肌肉、子宫、卵子和 内淋巴分泌。这也引入了一些基本问题，如 这些器官的生理学。特别是，在肌肉方面，我们将研究二氧化碳 产酶抑制后排出；子宫内着床 环境；在卵子中，辐射日冕的分散；在内淋巴中 分泌物的速度和特征。II.我们将研究二氧化碳在 中性分泌物(NaC L)与肾脏能否有H+输出 独立于二氧化碳系统。三、新型磺胺类缓蚀剂联合 将开发脂类和水的溶解性。药物酶的研究进展 将追求动力学，注意“非竞争性”抑制，以及 三种C.A.同工酶之间的差异。四、我们希望将 线粒体C.A.，以及脑髓鞘中的酶，相对于 Kcat、Km和对磺胺类药物的敏感性。五、我们的规划 为了研究两栖动物亚目的气体交换和酸碱平衡， 多齿类，既没有肺也没有鳃，完全通过 皮肤。它们也是唯一缺乏红细胞C.A.的成年脊椎动物。

项目成果

Association Between Walking for Exercise and Symptomatic and Structural Progression in Individuals With Knee Osteoarthritis: Data From the Osteoarthritis Initiative Cohort.

• DOI: 10.1002/art.42241
• 发表时间: 2022-10
• 期刊: ARTHRITIS & RHEUMATOLOGY
• 影响因子: 13.3
• 作者: Lo, Grace H.;Vinod, Surabhi;Richard, Michael J.;Harkey, Matthew S.;McAlindon, Timothy E.;Kriska, Andrea M.;Rockette-Wagner, Bonny;Eaton, Charles B.;Hochberg, Marc C.;Jackson, Rebecca D.;Kwoh, C. Kent;Nevitt, Michael C.;Driban, Jeffrey B.
• 通讯作者: Driban, Jeffrey B.

A longitudinal comparative study of falls in persons with knee arthroplasty and persons with or at high risk for knee osteoarthritis.

对膝关节置换术患者和膝骨关节炎患者或高风险患者跌倒的纵向比较研究。

• DOI: 10.1093/ageing/afw126
• 发表时间: 2016
• 期刊: Age and ageing
• 影响因子: 6.7
• 作者: Riddle,DanielL;Golladay,GregoryJ
• 通讯作者: Golladay,GregoryJ

Angiotensin-Converting Enzyme Inhibitor Use and Incident Frailty: A Longitudinal Cohort Study.

血管紧张素转换酶抑制剂的使用和事​​件衰弱：一项纵向队列研究。

• DOI: 10.1007/s40266-019-00642-3
• 发表时间: 2019
• 期刊: Drugs & aging
• 影响因子: 2.8
• 作者: Veronese,Nicola;Stubbs,Brendon;Smith,Lee;Maggi,Stefania;Jackson,SarahE;Soysal,Pinar;Demurtas,Jacopo;Celotto,Stefano;Koyanagi,Ai
• 通讯作者: Koyanagi,Ai

Prognostic value of coping strategies in a community-based sample of persons with chronic symptomatic knee osteoarthritis.

• DOI: 10.1016/j.pain.2013.08.012
• 发表时间: 2013-12
• 期刊: Pain
• 影响因子: 7.4
• 作者: Alschuler KN;Molton IR;Jensen MP;Riddle DL
• 通讯作者: Riddle DL

Relationship Between Magnetic Resonance Imaging Features and Knee Pain Over Six Years in Knees Without Radiographic Osteoarthritis at Baseline.

• DOI: 10.1002/acr.24394
• 发表时间: 2021-11
• 期刊: Arthritis care & research
• 影响因子: 4.7
• 作者: Magnusson K;Turkiewicz A;Kumm J;Zhang F;Englund M
• 通讯作者: Englund M