Long-term prognosis and management of clinically ill infants :"Fetal origin of adult disease" hypothesis

• Project/Area Number: 21591314
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Okayama University (2010-2011); University of Fukui (2009)
• Principal Investigator: TSUKAHARA Hirokazu 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (90207340)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 病的新生児 / 成人病 / 一酸化窒素 / 酸化ストレス / 生体マーカー / 小児疾患 / レドックス / 広汎性発達障害 / フェニルケトン尿症 / 脳障害 / 骨減少症 / 早産低出生体重児 / 成人病胎児期発症説 / asymmetric dimethylarginine / 肝内門脈-体静脈シャント / 高シトルリン血症 / 高アンモニア血症 / シトリン欠損症 / 動物モデル

Research Abstract

We have established several oxidative stress markers such as NOx, ADMA, and 8-OHdG in neonates, infants, and children. Measurement of these parameters enables us to evaluate NO-ADMA system and oxidative environment non-invasively and sequentially in children with various disorders. Rapid test for 8-OHdG measurement is also available. Further studies using these procedures are in progress in the clinical field.

Research Products

• [Journal Article] Multiple biomarkers for oxidative stress in patients with brain disorders (2012)
  • Author(s): Tsukahara H, Fujii Y, Hayashi Y, Morishima T
  • Journal Title: J Neurol Sci Volume: 313(1-2) Pages: 196-196
  • Peer Reviewed
• [Journal Article] Activation of Akt is associated with poor prognosis and chemotherapeutic resistance in pediatric B-precursor acute lymphoblastic leukemia (2012)
  • Author(s): Morishita N, Tsukahara H, Chayama K, Ishida T, Washio K, Miyamura T, Yamashita N, Oda M, Morishima T
  • Journal Title: Pediatr Blood Cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Oxidative stress biomarkers in pediatric medicine : A 2011 update (2012)
  • Author(s): Tsukahara H
  • Journal Title: Systems Biology of Free Radicalsand Anti-Oxidants Volume: (in press)
  • Peer Reviewed
• [Journal Article] Redox modulatory factors of human breast milk, Dietary and nutritionalaspects of human breast milk (2012)
  • Author(s): Tsukahara H
  • Volume: (in press)
  • Peer Reviewed
• [Journal Article] Evaluation of oxidative stress status in children with pervasive developmental disorder and attention deficit hyperactivity disorder usingurinary-specific biomarkers (2011)
  • Author(s): Kawatani M, Tsukahara H, Mayumi M
  • Journal Title: Redox Rep Volume: 16 Pages: 45-6
  • Peer Reviewed
• [Journal Article] CD36 deficiency predisposing young children to fasting hypoglycemia (2011)
  • Author(s): Nagasaka H, Yorifuji T, Takatani T, Okano Y, Tsukahara H, Yanai H, Hirano K, Hui SP, Hirayama S, Ito T, Chiba H, Miida T
  • Journal Title: Metabolism Volume: 60(6) Pages: 881-887
  • Peer Reviewed
• [Journal Article] Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adultswith phenylketonuria (2011)
  • Author(s): Sanayama Y, Nagasaka H, Takayanagi M, Ohura T, Sakamoto O, Ito T, Ishige-Wada M, Usui H, Yoshino M, Ohtake A, Yorifuji T, Tsukahara H, Hirayama S, Miida T, Fukui M, Okano Y
  • Journal Title: Mol Genet Metab Volume: 103(3) Pages: 220-225
  • Peer Reviewed
• [Journal Article] Cross-sectional study of bone metabolism along with nutrition in adult classical phenylketonuric patients diagnosed byneonatal screening (2011)
  • Author(s): Nagasaka H, Tsukahara H, Takatani T, Sanayama Y, Takayanagi M, Ohura T, Sakamoto O, Ito T, Wada M, Yoshino M, Ohtake A, Yorifuji T, Hirayama S, Miida T, Fujimoto H, Mochizuki H, Hattori T, Okano Y
  • Journal Title: J Bone Miner Metab Volume: 29(6) Pages: 737-743
  • Peer Reviewed
• [Journal Article] Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria (2011)
  • Author(s): Sanayama Y, et al
  • Journal Title: Mol Genet Metab Volume: 103 Pages: 220-225
  • Peer Reviewed
• [Journal Article] Cross-sectional study of bone metabolism with nutrition in adult classical phenylketonuric patients diagnosed by neonatal screening (2011)
  • Author(s): Nagasaka H, et al
  • Journal Title: J Bone Miner Metab Volume: 29 Pages: 737-743
  • Peer Reviewed
• [Journal Article] CD36 deficiency predisposing young children to fasting hypoglycemia (2011)
  • Author(s): Nagasaka H, et al
  • Journal Title: Metabolism Volume: 60 Pages: 881-887
  • Peer Reviewed
• [Journal Article] Evaluation of oxidative stress status in children with pervasive developmental disorder and attention deficit hyperactivity disorder using urinary-specific biomarkers (2011)
  • Author(s): Kawatani M, et al
  • Journal Title: Redox Rep Volume: 16 Pages: 45-46
  • Peer Reviewed
• [Journal Article] Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt (2010)
  • Author(s): Nagasaka H, Okano Y, Aizawa M, Miida T, Yorifuji T, Tajima G, Sakura N, Takatani T, Sanayama Y, Sugamoto K, Mayumi M, Kobayashi K, Hirano K, Takayanagi M, Tsukahara H
  • Journal Title: Metabolism Volume: 59(1) Pages: 107-113
  • Peer Reviewed
• [Journal Article] Asymmetric dimethylarginine, an endogenous NO synthase inhibitor, in human breast milk (2010)
  • Author(s): Tsukahara H, Nagasaka H
  • Journal Title: Early Hum Dev Volume: 86(2) Pages: 69-70
  • Peer Reviewed
• [Journal Article] Coupling of the citrulline recycling to endothelial NO production (2010)
  • Author(s): Tsukahara H, Nagasaka H, Tokuriki S, Mayumi M
  • Journal Title: Mol Genet Metab Volume: 99(4) Pages: 438-438
  • Peer Reviewed
• [Journal Article] Imagesin emergency medicine (2010)
  • Author(s): Nishijima K, Takahashi J, Yamamoto M, Orisaka M, Suzuki C, Tsukahara H, Shukunami K, Kurokawa T, Yoshida Y, Kotsuji F
  • Journal Title: Ann Emerg Med Volume: 55(5) Pages: 483-490
  • Peer Reviewed
• [Journal Article] Favorable effect of 4-phenylacetate on liver functions attributable to enhanced bile salt export pump expression in ornithine transcarbamylase-deficient children (2010)
  • Author(s): Nagasaka H, Yorifuji T, Kobayashi K, Takikawa H, Komatsu H, Inui A, Fujisawa T, Miida T, Tsukahara H, Takatani T, Hayashi H
  • Journal Title: Mol Genet Metab Volume: 100(2) Pages: 123-128
  • Peer Reviewed
• [Journal Article] Favorable effect of 4-phenylacetate on liver functions attributable to enhanced bile salt export pump expression in ornithine transcarbamylase-deficient children (2010)
  • Author(s): Nagasaka H, et al.
  • Journal Title: Mol Genet Metab Volume: 100 Pages: 123-128
  • Peer Reviewed
• [Journal Article] Coupling of the citrulline recycling to endothelial NO production (2010)
  • Author(s): Tsukahara H, et al.
  • Journal Title: Mol Genet Metab Volume: 99 Pages: 438-438
  • Peer Reviewed
• [Journal Article] Asymmetric dimethylarginine, an endogenous NO synthase inhibitor, in human breast milk (2010)
  • Author(s): Tsukahara H, et al.
  • Journal Title: Early Hum Dev Volume: 86 Pages: 69-70
  • Peer Reviewed
• [Journal Article] Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymplomatic children with congenital portosystemic venous shunt (2010)
  • Author(s): Nagasaka H, et al.
  • Journal Title: Metabolism Volume: 59 Pages: 107-113
  • Peer Reviewed
• [Journal Article] Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt (2010)
  • Author(s): Nagasaka H, et al.
  • Journal Title: Metabolism 59 Pages: 107-113
  • Peer Reviewed
• [Journal Article] Effects of bezafibrate on dyslipidemia with cholestasis in children with familial intrahepatic cholestasis-1 deficiency manifesting progressive familial intrahepatic cholestasis (2009)
  • Author(s): Nagasaka H, Yorifuji T, Hirano K, Ota A, Toyama-Nakagawa Y, Takatani T, Tsukahara H, Kobayashi K, Takayanagi M, Inomata Y, Uemoto S, Miida T
  • Journal Title: Metabolism Volume: 58(1) Pages: 48-54
  • Peer Reviewed
• [Journal Article] Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects (2009)
  • Author(s): Nagasaka H, Tsukahara H, Yorifuji T, Miida T, Murayama K, Tsuruoka T, Takatani T, Kanazawa M, Kobayashi K, Okano Y, Takayanagi M
  • Journal Title: Metabolism Volume: 58(3) Pages: 278-282
  • Peer Reviewed
• [Journal Article] Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even duringthe silent period (2009)
  • Author(s): Nagasaka H, Okano Y, Tsukahara H, Shigematsu Y, Momoi T, Yorifuji J, Miida T, Ohura T, Kobayashi K, Saheki T, Hirano K, Takayanagi M, Yorifuji T
  • Journal Title: Mol Genet Metab Volume: 97(1) Pages: 21-26
  • Peer Reviewed
• [Journal Article] Lipoprotein profiles in children with two common cholesteryl ester transfer protein gene mutations, D442G and I14A, during the first year of life (2009)
  • Author(s): Nagasaka H, Yorifuji T, Momoi T, Yorifuji J, Hirano K, Ota A, Takatani T, Tsukahara H, Takayanagi M, Kobayashi K, Chiba H, Sato Y, Miida T
  • Journal Title: Clin Chim Acta Volume: 406(1-2) Pages: 52-56
  • Peer Reviewed
• [Journal Article] Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period (2009)
  • Author(s): Nagasaka H, et al.
  • Journal Title: Mol Genet Metab 97 Pages: 21-26
  • Peer Reviewed
• [Journal Article] Lipoprotein profiles in children with two common cholesteryl ester transfer protein gene mutations, D442G and I14A, during the first year of life (2009)
  • Author(s): Nagasaka H, et al.
  • Journal Title: Clin Chim Acta 406 Pages: 52-56
  • Peer Reviewed
• [Presentation] 酸化ストレスの生体マーカー (2011)
  • Author(s): 塚原宏一
  • Organizer: 第49回日本小児感染症学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2011-11-29
• [Presentation] 小児科領域におけるレドックスマーカー検査の現況 (2011)
  • Author(s): 塚原宏一
  • Organizer: 第58回日本臨床検査医学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2011-11-18
• [Presentation] 酸化ストレスの生体マーカー-最近の進歩 (2011)
  • Author(s): 塚原宏一
  • Organizer: 第43回小児感染症学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2011-10-29
• [Presentation] 腎臓関連の臨床検査の読み方・考え方 (2011)
  • Author(s): 塚原宏一
  • Organizer: 第8回南大阪小児腎疾患カンファレンス
  • Place of Presentation: 大阪
  • Year and Date: 2011-07-23
• [Presentation] 血管生物学の基礎と臨床 (2011)
  • Author(s): 塚原宏一
  • Organizer: 平成23年岡山大学小児科同門会(「友周会」)
  • Place of Presentation: 岡山
  • Year and Date: 2011-03-13
• [Presentation] 血管生物学の基礎と臨床 (2011)
  • Author(s): 塚原宏一
  • Organizer: 平成23年福井県小児科医会学術講演会
  • Place of Presentation: 福井
  • Year and Date: 2011-03-12
• [Presentation] 新生児における循環の適応生理とそれに基づいた輸液戦略 (2011)
  • Author(s): 塚原宏一
  • Organizer: 第25回岡山新生児研究会
  • Place of Presentation: 岡山
  • Year and Date: 2011-02-12
• [Presentation] 酸化ストレスマーカーの臨床と研究:小児科領域における臨床的意義 (2010)
  • Author(s): 塚原宏一
  • Organizer: 島根大学医学部附属病院小児科セミナー
  • Place of Presentation: 島根
  • Year and Date: 2010-12-07
• [Presentation] ありふれた臨床検査から読めること・考えられること (2010)
  • Author(s): 塚原宏一
  • Organizer: 第10回山陽小児臨床懇話会(鯉操会)
  • Place of Presentation: 広島
  • Year and Date: 2010-11-20
• [Presentation] 川崎病の血管障害マーカー (2010)
  • Author(s): 塚原宏一
  • Organizer: 第6回岡山川崎病研究会
  • Place of Presentation: 岡山
  • Year and Date: 2010-10-30
• [Presentation] 川崎病の血管障害マーカー (2010)
  • Author(s): 塚原宏一
  • Organizer: 第6回川崎病研究会
  • Place of Presentation: 岡山
  • Year and Date: 2010-10-30
• [Presentation] 小児における諸臓器の成熟-小児は小さな大人ではない! (2010)
  • Author(s): 塚原宏一
  • Organizer: 第16回日本小児麻酔学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-09-18
• [Presentation] 小児の骨代謝:新生児・未熟児を中心に (2010)
  • Author(s): 塚原宏一
  • Organizer: 第9回山口県こどもの成長を考える会
  • Place of Presentation: 山口
  • Year and Date: 2010-07-16
• [Presentation] 窒素 (N) と酸素 (0) の化学・生物学 (2009)
  • Author(s): 塚原宏一
  • Organizer: 第6回日本臨床高気圧酸素・潜水医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-20