Clinical and Basic Study of Thioredoxin as a Oxidative Stress Marker in Patients with Obstructive Sleep Apnea

• Project/Area Number: 18603003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 睡眠学
• Research Institution: Kyoto University
• Principal Investigator: CHIN Kazuo Kyoto University, Graduate School of Medicine, Associate Professor (90197640)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Hajime Kyoto University, Graduate School of Medicine, Associate Professor (70303914)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,040,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
• Keywords: sleep apnea / obstructive sleep apnea / hypoxemia / intermittent hypoxia / Thioredoxin / oxidative stress / adiponectin / CPAP / 低酸素 / 肥満 / グレリン

Research Abstract

Obstructive sleep apnea (OSA) is associated with increased cardiovascular mortality, and oxidative stress was suggested to play an important role. The plasma thioredoxin (TRX) level is a novel oxidative stress market Adiponectin is an adipocyte-derived molecule with anti-inflammatory property. Plasma TRX and adiponectin levels were measured in 41 patients with severe OSA before (n=41) and after (n=27) nasal continuous positive airway pressure (nCPAP) therapy for one month and 12 subjects without OSA (Non-OSA group). The TRX level was significantly higher (p=0.02) and adiponectin level was significantly lower (p=0.02) in the OSA group than in the Non-OSA group. After one month of nCPAP treatment (n=27), the TRX level significantly decreased (p=0.03) and adiponectin level significantly increased (p=0.03). Among the 53 subjects (41 OSA + 12 Non-OSA subjects), the TRX level was positively correlated with respiratory disturbance index (p=0.002) and percentage of time with SaO_2<90% (p=0.002). The adiponectin level, but not the TRX level, was correlated with BMI (p = 0.02). Plasma TRX has the potential to be a unique marker for evaluating oxidative stress in OSA patients and monitoring the effectiveness of nCPAP therapy. Thus, OSA related hypoxemia (intermittent hypoxemia) which mimics reperfusion-reoxygenation may induce tissue injury as an oxidative stress. To investigate effects of intermittent hypoxia as an oxidative stress on cells, we made an instrument which had two chambers : hypoxia and normoxia chambers. Each chamber has preconditional medium equilibrated with gases : O2, CO2 and N2. Thus, putting cells into each preconditional medium, we can make intermittent hypoxia condition to cells. Using this instrument, we will do several cell experiments under intermittent hypoxia in the future.

Research Products

• [Journal Article] Acylated ghrelin level in patients with obstructive sleep apnoea before and after nasal CPAP treatment. (2008)
  • Author(s): Takahashi K, Chin K. Akamizu T, Morita S, Sumi K, Oga T, Matsumoto H, Niimi A, Tsuboi T, Fukuhara S, Kangawa K, Mishima M.
  • Journal Title: Respirology (in press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Plasma thioredoxin, a novel oxidative stress marker, in patients with obstructive sleep apnea before and after nasal continuous positive airway pressure. (2008)
  • Author(s): Takahashi K, Chin K, Nakamura H, Morita S, Sumi K, Oga T, Matsumoto H, Niimi A, Fukuhara S, Yodoi J, Mishima M.
  • Journal Title: Antioxidants & Redox Signaling 10
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Plasma thioredoxin, a novel oxidative stress marker, in patients with obstructive sleep apnea before and after nasal continuous positive airway pressure (2008)
  • Author(s): Takahashi, K., Chin, K., Nakamura, H., Morita, S., Sumi, K., Oga, T., Matsumoto, H., Niimi, A., Fukuhara, S., Yodoi, J., Mishima, M
  • Journal Title: Antioxidants & Redox Signaling 10 Pages: 715-726
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sleep-disordered breathing in the usual lifestyle setting as detected with home monitoring in a Japanese male working population (2008)
  • Author(s): Nakayama-Ashida, Y., Takegami, M., Chin, K., Sumi, K., Nakamura, T., Takahashi, K., Wakamura, T., Horita, S., Oka, Y., Minami, I., Fukuhara, S., Kadotani, H
  • Journal Title: Sleep 31 Pages: 419-425
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Plasma thioredoxin, a novel oxidative stress marker, in patients with obstructive sleep apnea before and after nasal continuous positive airway pressure. (2008)
  • Author(s): Takahashi K, Chin K, et. al.
  • Journal Title: Antioxidants & Redox Signaling . (In press)
• [Journal Article] Acylated ghrelin level in patients with obstructive sleep apnoea before and after nasal CPAP treatment. (2008)
  • Author(s): Takahasni K, Cnin K, et. al.
  • Journal Title: Respirology . (In press)
• [Journal Article] Sleep-disordered breathing in the usual lifestyle setting as detected with home monitoring in a Japanese male working population. (2008)
  • Author(s): Nakayama-Ashida Y, Takegami M, Chin K, et. al.
  • Journal Title: Sleep . (In press)
• [Journal Article] Sleep-disordered breathing in the usual lifestyle setting as detected with home monitoring in a Japanese male working population. (2007)
  • Author(s): Nakayama-Ashida Y, Takegami M, Chin K, Sumi K, Nakamura T, Takahasli K, Wakamura T, Horita S, Oka Y, Minami I, Fukuhara S, Kadotani H.
  • Journal Title: Sleep 31
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Noninvasive ventilation for pediatric patients under 1 year of age after cardiac surgery. (2007)
  • Author(s): Chin K, Takahashi K, Ohmori K, Iwasa T, Matsumoto H, Niimi A, Doi H, Ikeda T, Nakahata T, Komeda M, Mishima M.
  • Journal Title: J Thoracic Cardiovascular Surgery 134 Pages: 260-261
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 睡眠時無吸症候群. ガイドラインに基づいたcommon disease診療. (2007)
  • Author(s): 陳 和夫
  • Journal Title: 臨床研修プラクティス. 4
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Noninvasive ventilation for pediatric patients under 1 year of age after cardiac surgery (2007)
  • Author(s): Chin, K., Takahashi, K., Ohmori, K., Iwasa, T., Matsumoto, H., Niimi, A., Doi, H., Ikeda, T., Nakahata, T., Komeda, M., Mishima, M
  • Journal Title: J Thoracic Cardiovascular Surgery 134 Pages: 260-261
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Falls in blood pressure in patients with obstructive sleep apnoea after long-term nasal continuous posidve airway pressure treatment. (2006)
  • Author(s): Chin K, Nakamura T, Fukuhara S, Takahashi K, Sumi K, Matsumoto H, Niimi A, Mishima M, Nakamura T.
  • Journal Title: Journal of Hypertension 24 Pages: 2091-2099
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Clinical characteristics of obesity-hypoventilation syndrome in Japan: a Multi-center study. (2006)
  • Author(s): Akashiba T, Akahoshi T, Kawahara S, Uematsu A, Katsura K, Sakurai S, Murata A, Sakakibara H, Chin K, Hida W, Nakamura H.
  • Journal Title: Inter Med 45 Pages: 1121-1125
  • NAID: 130000076625
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Negative-pressure pulmonary edema after resection of mediastinum thyroid goiter. (2006)
  • Author(s): Ikeda H, Asato R, Chin K, Kojima T, Tanaka S, Omori K, Hiratsuka Y, Ito J.
  • Journal Title: Acta Oto-Laryngologica 126 Pages: 886-888
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 高齢者睡眠時無呼吸(SAS)の治療は持続陽圧呼吸(CPAP)が第一選択である。(Pro)第48回日本老年医学会学術集会記録(老齢医療におけるControversy) (2006)
  • Author(s): 陳 和夫
  • Journal Title: 日本老年学会誌 43 Pages: 734-737
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 日本語版the Epworth Sleepiness Scale(JESS)-これまで使用されていた多くの「日本語版」との主な差異と改訂- (2006)
  • Author(s): 福原俊一、竹上未紗、鈴鴨よしみ、陳 和夫、井上雄一、角谷 寛、岡 靖哲、野口裕之、脇田貴文、並川 努、中村敬哉、三嶋理晃、Murray W. Johns.
  • Journal Title: 日本呼吸器学会誌 44 Pages: 896-898
  • NAID: 10018401023
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Falls in blood pressure inpatients with obstructive sleep apnoea after long-term nasal continuous positive airway pressure treatment (2006)
  • Author(s): Chin, K., Nakamura, T., Fukuhara, S., Takahashi, K., Sumi, K., Matsumoto, H., Niimi, A., Mishima, M., Nakamura, T
  • Journal Title: Journal of Hypertension 24 Pages: 2091-2099
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Elevated heart rate before treatment in patients with obstructive sleep apnoea-hypopnoea (2006)
  • Author(s): Sumi, K., Chin, K., Takahashi, K., Nakamura, T., Matsumoto, H., Mimi, A., Mishima, M
  • Journal Title: Quarterly Journal of Medicine 99 Pages: 545-553
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical characteristics of obesity-hypoventilation syndrome in Japan : a Multi-center study (2006)
  • Author(s): Akashiba, T., Akahoshi, T., Kawahara, S., Uematsu, A., Katsura, K., Sakurai, S., Murata, A., Sakakibara, H., Chin, K., Hida, W., Nakamura, H
  • Journal Title: Inter Med 45 Pages: 1121-1125
  • NAID: 130000076625
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Negative-pressure pulmonary edema after resection of mediastinum thyroid goiter (2006)
  • Author(s): Ikeda, H., Asato, R., Chin, K., Kojima, T., Tanaka, S., Omori, K., Hiratsuka, Y., Ito, J
  • Journal Title: Acta Oto-Laryngologica 126 Pages: 886-888
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Falls in blood pressure in patients with obstructive sleep apnoea after long-term nasal continuous positive airway pressure treatment. (2006)
  • Author(s): Chin K, Nakamura T, Fukuhara S, Takahashi K, Sumi K, Matsumoto H, Niimi A, Mishima M, Nakamura T
  • Journal Title: Journal of Hypertension 24 Pages: 2091-2099
• [Journal Article] Elevated heart rate before treatment in patients with obstructive sleep apnoea-hypopnoea. (2006)
  • Author(s): Sumi K, Chin K, Takahashi K, Nakamura T, Matsumoto H, Niimi A, Mishima M
  • Journal Title: Quarterly Journal of Medicine 99 Pages: 545-553
• [Journal Article] Clinical characteristics of obesity-hypoventilation syndrome in Japan : a Multi-center study. (2006)
  • Author(s): Akashiba T, Akahoshi T, Kawahara S, Uematsu A, Katsura K, Sakurai S, Murata A, Sakakibara H, Chin K, et al.
  • Journal Title: Inter Med 45 Pages: 1121-1125
  • NAID: 130000076625
• [Journal Article] Negative-pressure pulmonary edema after resection of mediastinum thyroid goiter. (2006)
  • Author(s): Ikeda H, Asato R, Chin K, Kojima T, Tanaka S, Omori K, Hiratsuka Y, Ito J
  • Journal Title: Acta Oto-Laryngologica 126 Pages: 886-888
• [Journal Article] 高齢者睡眠時無呼吸(SAS)の治療持続陽圧呼吸(CPAP)が第一選択である。(Pro)第48回日本老年医学会学術集会記録(老齢医療におけるControversy) (2006)
  • Author(s): 陳 和夫
  • Journal Title: 日本老年学会誌 43 Pages: 734-737
• [Journal Article] 日本語版the Epworth Sleepiness Scale(JESS)-これまで使用されていた多くの「日本語版」との主な差異と改訂- (2006)
  • Author(s): 福原俊一, 竹上未紗, 鈴鴨よしみ, 陳 和夫, 井上雄一, 角谷 寛, 岡 靖哲, 野ロ裕之, 脇田貴文, 並川 努, 中村敬哉, 三嶋理晃, Murray W. Johns.
  • Journal Title: 日本呼吸器学会誌 44 Pages: 896-898
  • NAID: 10018401023
• [Journal Article] Elevated heart rate before treatment in patients with obstructive sleep apnoea-hypopnoea (2005)
  • Author(s): Sumi K, Chin K Takahashi K, Nakamura T, Matsumoto H, Niimi A, Mishima M. Elevated heart rate before treatment in patients with obstructive sleep apnoea-hypopnoea.
  • Journal Title: Quarterly Journal of Medicine 99
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Acylated ghrelin level in patients with obstructive sleep apnoea before and after nasal CPAP treatment
  • Author(s): Takahashi, K., Chin, K., Akamizu, T., Morita, S., Sumi, K., Oga, T., Matsumoto, H., Niimi, A., Tsuboi, T., Fukuhara, S., Kangawa, K., Mishima, M
  • Journal Title: Respirology (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 閉塞型睡眠時無呼吸と持続陽圧呼吸の血小板凝集能への効果の検討. (2007)
  • Author(s): 小賀 徹、陳 和夫、角 謙介、高橋憲一、半田知宏、渡辺 創、三嶋理晃、北 徹、堀内久徳
  • Organizer: 第32回日本睡眠学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-08
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] The influence of sleep-disordered breathing on the occurrence of metabolic syndrome from a population based study. (2007)
  • Author(s): Chin K, Takahashi K, Takegami K, Oga T, Nakayama-Asida Y, Oka. Y, Wakamura T, Mishima M, Fukuhara S, Kadotani H.
  • Organizer: 5th Congress of the World Federation of Sleep Research and Sleep Medicine Societies.
  • Place of Presentation: Cairns, Australia.
  • Year and Date: 2007-09-03
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] The influence of sleep-disordered breathing on the occurrence of metabolic syndrome from a population based study (2007)
  • Author(s): Chin, K., Takahashi, K., Takegami, K., Oga, T., Nakayama-Asida, Y., Oka, Y., Wakamura, T., Mishima, M., Fukuhara, S., Kadotani, H
  • Organizer: 5th Congress of the World Federation of Sleep Research and Sleep Medicin Societies
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2007-09-03
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] NPPVの院内急性期使用から予防使用に関連してワークショップ:NPPV普及のための教育とその標準化. (2007)
  • Author(s): 陳 和夫
  • Organizer: 第29回日本呼吸療法医学会
  • Place of Presentation: 岡山
  • Year and Date: 2007-07-06
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Elevated acylated ghrelin may accelerate body weight gain in patient with obstructive sleep apnea before treatment (2007)
  • Author(s): Takahashi, K., Chin, K., Akamizu, T., Sumi, K., Nakamura, T., Kangawa, K., Mishima, M
  • Organizer: ATS 2006 International Conference
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2007-05-22
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Improvement in increased platelet aggregability in patients with obstructive sleep apnea by nasal continuous positive airway pressure treatment. (2007)
  • Author(s): Chin K, Sumi K, Horiuchi H, Takahashi K, Nakamura T, KitaT, Mishima M.
  • Organizer: ATS 2007 International Conference
  • Place of Presentation: アメリカ・サンフランシスコ
  • Year and Date: 2007-05-21
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Improvement in increased platelet aggregability in patients with obstructive sleep apnea by nasal continuous positive airway pressure treatment (2007)
  • Author(s): Chin, K., Sumi, K., Horiuchi, H., Takahashi, K., Nakamura, T., Kita, T., Mishima, M
  • Organizer: ATS 2007 International Conference
  • Place of Presentation: California, USA
  • Year and Date: 2007-05-21
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 高齢者睡眠時無呼吸(SAS)の治療は持続陽圧呼吸(CPAP)が第一選択である。Pro.老年医療におけるControversy. (2006)
  • Author(s): 陳 和夫
  • Organizer: 第48回日本老年医学会
  • Place of Presentation: 石川県・金沢
  • Year and Date: 2006-06-08
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Elevated acylated ghrelin may accelerate body weight gain in patient with obstructive sleep apnea before treatment. (2006)
  • Author(s): Takahashi K, Chin K, Akamizu T, Sumi K, Nakamura T, Kangawa K, Mishima M.
  • Organizer: ATS 2006 International Conference
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2006-05-22
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 閉塞型睡眠時無呼吸症候群(OSAS)患者の高血圧症合併の有無による長期経鼻持続気道陽圧(nCPAP)療法の降圧効果. (2006)
  • Author(s): 中村敬哉、陳 和夫、高橋憲一、角 謙介、福原俊一、三嶋理晃.
  • Organizer: 第31回日本睡眠学会
  • Place of Presentation: 滋賀県・大津
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 閉塞型睡眠時無呼吸症候群におけるアポリポ蛋白の検討. (2006)
  • Author(s): 高橋憲一、陳 和夫、角 謙介、中村敬哉、三嶋理晃.
  • Organizer: 第31回日本睡眠学会
  • Place of Presentation: 滋賀県・大津
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 日本語版The Epworth Sleepiness(ESS)の開発・項目選択・検証〜_古典的モデルと項目応答理論を活用して〜_. (2006)
  • Author(s): 竹上末紗、鈴鴨よしみ、野口裕之、脇田貴文、陳 和夫、中村敬哉、角谷 寛、井上雄一、岡 靖哲、並川 努、Murray Johns、福原 俊一
  • Organizer: 第31回日本睡眠学会
  • Place of Presentation: 滋賀県・大津
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 睡眠時無呼吸症候群とメタボリックシンドローム.シンポジウム「睡眠と循環制御」 (2006)
  • Author(s): 陳 和夫
  • Organizer: 第27回日本循環制御医学会総会
  • Place of Presentation: 東京
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 在宅人工呼吸療法の適応、呼吸器疾患最新の治療2007-2009(工藤翔二、中田紘一郎、貫和敏博編)161-163 (2007)
  • Author(s): 陳和夫
  • Total Pages: 506
  • Publisher: 南江堂
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 呼吸調節機能検査、夜間睡眠モニター、「内科学」(金沢一郎、北原光夫、山口 徹、小俣政男編)1015-1017 (2007)
  • Author(s): 陳 和夫
  • Total Pages: 728
  • Publisher: 朝倉書店
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 呼吸調節機能検査、夜間睡眠モニター、「内科学」(金沢一郎、北原光夫、山口 徹、小俣政男編)1015-1017 (2006)
  • Author(s): 陳 和夫
  • Total Pages: 2994
  • Publisher: 医学書院
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 閉塞性睡眠時無呼吸・低呼吸症候群 どの観点から取り組むか「睡眠医学を学ぶために 専門医の伝える実践睡眠医学」(立花直子、NPO法人大阪スリープヘルスネットワーク編)215-224 (2006)
  • Author(s): 陳 和夫
  • Total Pages: 338
  • Publisher: 永井書店
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 「呼吸の事典」有田秀穂編(総ページ数744の内の20頁) (2006)
  • Author(s): 陳 和夫
  • Total Pages: 744
  • Publisher: 朝倉書店