Study on establishing the precise measurement system for oxidative stress

• Project/Area Number: 18790543
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: 平野 綱彦 Wakayama Medical University, 医学部, 助教 (00382333)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
• Keywords: 呼吸器病学 / 慢性閉塞性肺疾患 / 窒素化ストレス / ニトロタイロシン / HPC / ECD法 / 喀痰 / テオフィリン / 酸化ストレス / 精密定量法 / 3-ニトロタイロシン / HPLC / 定量法 / 唾液 / 気道閉塞

Research Abstract

まず高速液体クロマトグラフィー(HPLC)に電気化学検出(ECD)を組み合わせた方法を用いた喀痰中の蛋白結合3-ニトロタイロシンの測定は窒素化ストレスの定量法として有益であり、気道・肺における窒素化ストレスの産生亢進がCOPDの発症や進展に関与していることを示した.次に実際に人において窒素化ストレスの制御がCOPDの気道炎症を改善すると仮定し、クロスオーバースタイルにてCOPD患者にテオフィリンを投与し、検討を行った.活性窒素種の測定に関して、上述のHPLC/ECD法による定量的な検討もあわせて行ったところ、テオフィリン投与群では、気道中の活性窒素種産生量が減少し、好中球性の気道炎症が抑制されることを見出し、同薬剤がCOPDの新たな抗炎症薬となる可能性が示唆された.今後は本システムを用いてCOPDの気道・肺炎症に関連する原因物質を特定し、その病的意義及び特異的に制御し得る薬剤の検証をすすめて、COPDの病態解明・治療効率の向上へ寄与できると考えられる.

Research Products

• [Journal Article] Prevalence of COPD in primary care clinics : correlation with non-respiratory diseases (2008)
  • Author(s): Minakata Y, Sugiura H, Yamagata T, Yanagisawa S, Ichikawa T, Koarai A, Akamatsu K, Hirano T, Matsunaga K, Ichinose M
  • Journal Title: Internal medicine 47(2) Pages: 77-82
  • Peer Reviewed
• [Journal Article] Comparison of bronchodilatory properties of transdermal and inhaled long-acting beta(2)-agonists (2008)
  • Author(s): Yamagata T, Hirano T, Sugiura H, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M
  • Journal Title: Pulm Pharmacol Ther 21(1) Pages: 160-5
  • Peer Reviewed
• [Journal Article] Peak Expiratory Flow Variability Adjusted by Forced Expiratory Volume in One Second is a Good Index for Airway Responsiveness in Asthmatics (2008)
  • Author(s): K. Matsuaga, M. Kanda, A. Hayata, S. Yanagisawa, T. Ichikawa, K. Akamatsu, A. Koarai, T. Hirano, H. Sugiura, Y. Minakata, M. Ichinose
  • Journal Title: Intern Med 47 Pages: 1107-1112
• [Journal Article] Peroxynitrite augments fibroblast-mediated tissue remodeling via myofibroblast differentiation (2008)
  • Author(s): T. Ichikawa, H. Sugiura, A. Koarai, S. Yanagisawa, M. Kanda, A. Hayata, K. Furukawa, K. Akamatsu, T. Hirano, M. Nakanishi, K. Matsunaga, Y. Minakata, M. Ichinose
  • Journal Title: Am J Physiol Lung Cell Mol Physiol 295 Pages: 800-808
  • Peer Reviewed
• [Journal Article] Prevalence of COPD in primary care clinics : Correlation with nonrespiratory diseases (2008)
  • Author(s): Minakata Y, Hirano T, et.al.
  • Journal Title: Intern Med 47 Pages: 77-82
  • Peer Reviewed
• [Journal Article] Comparison of bronchodilatory properties of transdermal and inhaled long-acting beta2-agonists (2008)
  • Author(s): Yamagata T, Hilano T, et.al.
  • Journal Title: Pulm Pharmacol Ther 21 Pages: 160-165
  • Peer Reviewed
• [Journal Article] Peak expiratory flow variability adjusted by forced expiratory volume in one second is a good index for airwav responsiveness in asthmatics (2008)
  • Author(s): Matsunaga K, Hirano T, et.al.
  • Journal Title: Inten Med 47 Pages: 1107-1112
  • Peer Reviewed
• [Journal Article] Peroxynitrite augments fibroblast-mediated tissue remodeling via myofi broblast differentiation (2008)
  • Author(s): Ichikawa T, Hirano T, et.al.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol 295 Pages: 800-808
  • Peer Reviewed
• [Journal Article] Overexpression of CD-11b and CXCR1 on Circulating Neutrophils : Its Possible Role in COPD (2007)
  • Author(s): T. Yamagata, H. Sugiura, T. Yokoyama, S. Yanagisawa, T. Ichikawa, K. Ueshima, K. Akamatsu, T. Hirano, M. Nakanishi, Y. Yamagata, K. Matsunaga, Y. Minakata, M. Ichinose
  • Journal Title: Chest 132 Pages: 890-899
  • Peer Reviewed
• [Journal Article] Improvement of pulmonary function and dyspnea by tiotropium in COPD patients using a transdermal β2-agonist (2007)
  • Author(s): K. Akamatsu, T. Yamagata, T. Takahashi, K. Miura, S. Maeda, Y. Yamagata, T. Ichikawa, S. Yanagisawa, K. Ueshima, T. Hirano, M. Nakanishi, K. Matsunaga, Y. Minakata, M. Ichinose
  • Journal Title: Pulm Pharm Ther 20 Pages: 701-707
  • Peer Reviewed
• [Journal Article] The Influence of Free 3-Nitrotyrosine and Saliva on the Quantitative Analysis of Protein-Bound 3-Nitrotyrosine in Sputum (2007)
  • Author(s): K. Ueshima, Y. Minakata, H. Sugiura, S. Yanagisawa, T. Ichikawa, K. Akamatsu, T. Hirano, M. Nakanishi, K. Matsunaga, T. Yamagata, M. Ichinose
  • Journal Title: Analytical Chemistry Insights 1 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Possible impact of salivary contamination on cytokine analysis in exhaled breath condensate (2007)
  • Author(s): T. Ichikawa, K. Matsunaga, Y. Minakata, S. Yanagisawa, K. Ueshima, K. Akamatsu, T. Hirano, M. Nakanishi, H. Sugiura, T. Yamagata, M. Ichinose
  • Journal Title: Analytical Chemistry Insights 2 Pages: 5-92
  • Peer Reviewed
• [Journal Article] 気管支喘息における呼気凝縮液中の炎症関連物質発現と呼吸生理パラメーターとの関連 (2007)
  • Author(s): 松永和人, 柳澤悟, 市川朋宏, 上嶋千史, 赤松啓一郎, 平野綱彦, 中西正典, 山縣俊之, 南方良章, 一ノ瀬正和
  • Journal Title: 呼吸 26 Pages: 2-4
  • Peer Reviewed
• [Journal Article] Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline (2006)
  • Author(s): T. Hirano, T. Yamagata, M. Gohda, Y. Yamagata, T. Ichikawa, S. Yanagisawa, K. Ueshima, K. Akamatsu, M. Nakanishi, K. Matsunaga, Y. Minakata, M.Ichikawa
  • Journal Title: Thorax 61 Pages: 761-766
  • Peer Reviewed
• [Journal Article] Airway cytokine expression measured by means protein array in exhaled breath condensate: Correlation with physiologic properties in asthmatic patients (2006)
  • Author(s): K. Matsunaga, S. Yanagisawa, T.Ichikawa, K. Ueshima, K. Akamatsu, T. Hirano, M. Nakanishi, T. Yamagata, Y. Minakata, M. Ichinose
  • Journal Title: J Allergy Clin Immunol 118 Pages: 84-90
  • Peer Reviewed
• [Journal Article] Two Cases of Asthma in Handicapped Elderly Persons in Which Assisted Inhalation Therapy Was Effective (2006)
  • Author(s): K. Matsunaga, S. Yanagisawa, T. Ichikawa, K. Ueshima, K. Akamatsu, T. Hirano, M. Nakanishi, T. Yamagata, Y. Minakata, M. Ichinose
  • Journal Title: Allergology International 55 Pages: 347-351
  • Peer Reviewed
• [Journal Article] 気道過敏性の簡便な臨床指標の検討 (2006)
  • Author(s): 松永和人, 柳澤悟, 市川朋宏, 上嶋千史, 赤松啓一郎, 平野綱彦, 中西正典, 山縣俊之, 南方良章, 一ノ瀬正和
  • Journal Title: 呼吸 25 Pages: 41-42
  • Peer Reviewed
• [Journal Article] COPD気道における微小血管透過性亢進 (2006)
  • Author(s): 南方良章, 柳澤悟, 市川朋宏, 上嶋千史, 赤松啓一郎, 平野綱彦, 中西正典, 松永和人, 山縣俊之, 一ノ瀬正和
  • Journal Title: 呼吸 25 Pages: 45-46
  • Peer Reviewed
• [Journal Article] COPD患者に対する新しいテオフィリンの効果の検討: 抗炎症作用とその機序 (2006)
  • Author(s): 郷田三賀子, 平野綱彦, 福井浩二, 山縣俊之, 山縣優子, 中西正典, 上嶋千史, 松永和人, 南方良章, 一ノ瀬正和
  • Journal Title: 和歌山医学 57 Pages: 8-13
  • NAID: 40007282874
  • Peer Reviewed
• [Presentation] Inhibition of reactive nitrogen species production in COPD airway : comparison inhaled corticosteroid and oral theophylline (2008)
  • Author(s): 平野綱彦
  • Organizer: 第76回和歌山医学会総会(青洲賞受賞記念講演)
  • Place of Presentation: 和歌山
  • Year and Date: 2008-07-06
• [Presentation] COPDにおける気道炎症と窒素化ストレス (2008)
  • Author(s): 平野綱彦
  • Organizer: 第48回日本呼吸器学会学術講演会(シンポジウム)
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-15
• [Presentation] 胸腔鏡で診断しえた悪性胸膜中皮種の2例 (2007)
  • Author(s): 平野綱彦, 中西宏公, 池田剛司
  • Organizer: 第36回和歌山肺癌研究会
  • Place of Presentation: 和歌山
  • Year and Date: 2007-07-07
• [Presentation] Comparison of Bronchodilator Propery between Inhaled and Transdermal β2-Stimutants (2006)
  • Author(s): T. Hirano, S. Yanagis wa, T. Ichikawa, K. Ueshima, M. Nakanishi, K. M tsunaga, T. Yamagata, Y. Minakata, M. Ichinose
  • Organizer: 11th Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2006-11-21
• [Book] COPDの病因と病態 (2008)
  • Author(s): 平野綱彦, 一ノ瀬正和
  • Publisher: 中外医学社
• [Book] 血液検査, 喀痰検査, 呼気ガス検査 (2008)
  • Author(s): 平野綱彦, 一ノ瀬正和
  • Publisher: 診断と治療96
• [Book] 血液検査、喀疾検査、呼気ガス検査 (2008)
  • Author(s): 平野綱彦、一ノ瀬正和
  • Publisher: 診断と治療
• [Book] COPDの病因と病態 (2008)
  • Author(s): 平野綱彦、一ノ瀬正和
  • Publisher: 中外医学社
• [Book] 薬物療法の基礎知識 気管支拡張薬 22. 抗コリン薬の種類・使用法. 高齢者診療のツボ COPD. 福地義之助編 (2006)
  • Author(s): 平野綱彦, 一ノ瀬正和
  • Publisher: 日本医事新報社