Mechanisms of abnormal iron metabolism in metabolic syndrome and its implications for new therapeutic strategies

• Project/Area Number: 21590959
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Hyogo Medical University
• Principal Investigator: TSUJINO Takeshi 兵庫医科大学, 医学部, 非常勤講師 (90283887)
• Co-Investigator(Kenkyū-buntansha): MASUYAMA Tohru 兵庫医科大学, 医学部, 教授 (70273670) ; KAWABATA Masaaki 兵庫医科大学, 医学部, 非常勤講師 (70411999) ; NAITO Yoshiro 兵庫医科大学, 医学部, 講師 (10446049)
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: メタボリックシンドローム / 鉄代謝 / 多血症 / インスリン抵抗性 / 高血圧 / 鉄 / 貧血 / メタボリックシンドローム. / nitrosative stress / 低酸素 / 貯蔵鉄 / 糖尿病性腎症 / 酸化ストレス / ピモニダゾール / レニン・アンジオテンシン系

Research Abstract

High body iron levels are found in type 2 diabetes mellitus(DM). Iron excess leads to tissue injury through free radical formation. We investigated the effect of iron restriction on diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty(OLETF) rats, a model of type 2 DM. In OLETF given high salt-high fat diet, iron restriction reduced systolic blood pressure, urinary excretion of protein and renal glomerular injury. Iron restriction suppressed oxidative stress and renin-angiotensin system in the kidney and attenuated renal hypoxia in the HFS+IR group compared to the HFS group. Iron restriction may be beneficial in prevention of nephropathy in type 2 DM.

Research Products

• [Journal Article] Impaired expression of duodenal iron transporters in Dahl salt-sensitive heart failure rats (2011)
  • Author(s): Naito Y, Tsujino T, Fujimori Y, Sawada H, Akahori H, Hirotani S, Ohyanagi M, Masuyama T.
  • Journal Title: J Hypertens Volume: 29(4) Pages: 741-8
  • Peer Reviewed
• [Journal Article] Dietary iron restriction prevents hypertensive cardiovascular remodeling in Dahl salt-sensitive rats (2011)
  • Author(s): Naito Y, Hirotani S, Sawada H, Akahori H, Tsujino T, Masuyama T.
  • Journal Title: Hypertension Volume: 57(3) Pages: 497-504
  • Peer Reviewed
• [Journal Article] Role of plasma aldosterone concentration in regression of left-ventricular mass following antihypertensive medication (2011)
  • Author(s): Yoshida C, Goda A, Naito Y, Nakaboh A, Matsumoto M, Otsuka M, Ohyanagi M, Hirotani S, Lee-Kawabata M, Tsujino T, et al
  • Journal Title: J Hypertens Volume: 29(2) Pages: 357-363
  • Peer Reviewed
• [Journal Article] Administration of angiotensin-converting enzyme inhibitors is associated with slow progression of mild aortic stenosis in Japanese patients (2011)
  • Author(s): Wakabayashi K, Tsujino T, et al
  • Journal Title: Heart Vessels Volume: 26(3) Pages: 252-7
  • Peer Reviewed
• [Journal Article] Preprocedural evaluation and endovascular treatment of iliofemoral artery disease without contrast media for patients with pre-existing renal insufficiency (2011)
  • Author(s): Kawasaki D, Fujii K, Fukunaga M, Fujii N, Masutani M, Kawabata ML, Tsujino T, et al
  • Journal Title: Circ J Volume: 75 Pages: 179-184
  • NAID: 10027425887
  • Peer Reviewed
• [Journal Article] Intraleaflet hemorrhage is associated with rapid progression of degenerative aortic valve stenosis (2011)
  • Author(s): Akahori H, Tsujino T, et al
  • Journal Title: Eur Heart J Volume: 32 Pages: 888-896
  • Peer Reviewed
• [Journal Article] Dietary iron restriction prevents hypertensive cardiovascular remodeling in dahl salt-sensitive rats (2011)
  • Author(s): Naito Y, Hirotani S, Sawada H, Akahori H, Tsujino T, Masuyama T
  • Journal Title: Hypertension Volume: 57(3) Pages: 497-504
  • Peer Reviewed
• [Journal Article] Endothelium-dependent coronary vasomotor response and neointimal coverage of zotarolimus-eluting stents 3 months after implantation (2011)
  • Author(s): Fujii K, Kawasaki D, Oka K, Akahori H, Fukunaga M, Sawada H, Masutani M, Lee-Kawabata M, Tsujino T, et al
  • Journal Title: Heart Volume: 97(12) Pages: 977-82
  • Peer Reviewed
• [Journal Article] The impact of pravastatin pre-treatment on periprocedural microcirculatory damage in patients undergoing percutaneous coronary intervention (2011)
  • Author(s): Fujii K, Kawasaki D, Oka K, Akahori H, Iwasaku T, Fukunaga M, Eguchi A, Sawada H, Masutani M, Lee-Kawabata M, Tsujino T, Ohyanagi M, Masuyama T
  • Journal Title: JACC Cardiovasc Interv Volume: 4(5) Pages: 513-20
  • Peer Reviewed
• [Journal Article] Involvement of bone morphogenetic protein-binding endothelial regulator in aortic valve stenosis (2011)
  • Author(s): Sawada H, Naito Y, Hirotani S, Akahori H, Iwasaku T, Eguchi A, Okuhara Y, Fujii A, Ohyanagi M, Mitsuno M, Miyamoto Y, Tsujino T, Masuyama T
  • Journal Title: Int J Cardiol Volume: 152(1) Pages: 107-109
  • Peer Reviewed
• [Journal Article] Determinants of plasma brain natriuretic peptide levels in untreated hypertensive patients (2011)
  • Author(s): Goda A, Nakao S, Tsujno T, et al
  • Journal Title: J Echocardiogr Volume: 9 Pages: 103-108
  • Peer Reviewed
• [Journal Article] Heart Failure with Preserved Ejection Fracationにおける左室内腔形態と予後との関連についての検討 (2011)
  • Author(s): 江口明世, 中坊亜由美, 合田亜希子, 正木充, 大塚美里, 吉田千佳子, 廣谷信一, 川端正明, 辻野健, 増山理
  • Journal Title: Jpn J Med Ultrasonics Volume: 38(2) Pages: 103-110
  • Peer Reviewed
• [Journal Article] 心・腎保護の観点からみた降圧治療においてアンジオテンシンII受容体拮抗薬に利尿薬を追加する意義 (2011)
  • Author(s): 奥田哲, 合田亜希子, 正木充, 中坊亜由美, 飯野貴子, 吉田千佳子, 廣谷信一, 大柳光正, 辻野健, 増山理
  • Journal Title: 日本心臓病学会誌 Volume: 6(3) Pages: 209-215
  • NAID: 10029839441
  • Peer Reviewed
• [Journal Article] 糖尿病,肥満と心不全 (2011)
  • Author(s): 松本実佳, 辻野健, 増山理
  • Journal Title: アディポサイエンス Volume: 8(1) Pages: 56-62
• [Journal Article] Iron Regulatory Hormone Hepcidin Decreases in Chronic Heart Failure Patients With Anemia. (2010)
  • Author(s): Matsumoto M, Tsujino T, et al.
  • Journal Title: Circ J Volume: 74 Pages: 301-6
  • NAID: 10025942465
  • Peer Reviewed
• [Journal Article] Increased interleukin-18 expression in nonrheumatic aortic valve stenosis. (2010)
  • Author(s): Naito Y, Tsujino T, et al.
  • Journal Title: Int J Cardiol Volume: 144 Pages: 260-63
  • Peer Reviewed
• [Journal Article] Hyperglycemia induced cell growth and gene expression via the serum response element through RhoA and Rho-kinase in vascular smooth muscle cells. (2010)
  • Author(s): Ishiko K, Tsujino T, et al.
  • Journal Title: Prep Biochem Biotechnol Volume: 40 Pages: 139-51
  • Peer Reviewed
• [Journal Article] OCT assessment of thin-cap fibroatheroma distribution in native coronary arteries. (2010)
  • Author(s): Fujii K, Tsujino T, et al.
  • Journal Title: JACC Cardiovasc Imaging Volume: 3(2) Pages: 168-75
  • Peer Reviewed
• [Journal Article] Increase in tissue and circulating pentraxin3 levels in patients with aortic valve stenosis. (2010)
  • Author(s): Naito Y, Tsujino T, et al.
  • Journal Title: Am Heart J Volume: 160(4) Pages: 685-91
  • Peer Reviewed
• [Journal Article] Increased serum neopterin in patients with nonrheumatic aortic valve stenosis. (2010)
  • Author(s): Naito Y, Tsujino T, et al.
  • Journal Title: Int J Cardiol Volume: 145(2) Pages: 360-1
  • Peer Reviewed
• [Journal Article] Augmented cannabinoid receptors expression in human aortic valve stenosis. (2010)
  • Author(s): Naito Y, Tsujino T, et al.
  • Journal Title: Int J Cardiol Volume: 145 Pages: 535-7
  • Peer Reviewed
• [Journal Article] Decrease in serum adiponectin levels in response to treatment predicts good prognosis in acute decompensated heart failure. (2010)
  • Author(s): Matsumoto M, Tsujino T, et al.
  • Journal Title: J Clin Hypertens (Greenwich) Volume: 12(11) Pages: 900-4
  • Peer Reviewed
• [Journal Article] Shinozuka K. Characterization of cardiac size and function in SHRSP. Z-Lepr(fa)/IzmDmcr rats, a new animal model of metabolic syndrome. (2010)
  • Author(s): Tada Y, Tsujino T, et al.
  • Journal Title: Biol Pharm Bull Volume: 33 Pages: 1971-6
  • Peer Reviewed
• [Journal Article] Preprocedural Evaluation and Endovascular Treatment of Iliofemoral Artery Disease Without Contrast Media for Patients With Pre-Existing Renal Insufficiency. (2010)
  • Author(s): Kawasaki D, Tsujino T, et al.
  • Journal Title: Circ J Volume: 75 Pages: 179-84
  • NAID: 10027425887
  • Peer Reviewed
• [Journal Article] Serum interleukin-6 and C-reactive protein are markedly elevated in acute decompensated heart failure patients with left ventricular systolic dysfunction. (2010)
  • Author(s): Matsumoto M, Tsujino T, et al.
  • Journal Title: Cytokine Volume: 49(3) Pages: 264-8
  • Peer Reviewed
• [Journal Article] The Mechanism of Distinct Diurnal Variations of Renin-Angiotens in System in Aorta and Heart of SpontaneouslyHypertensive Rats. (2009)
  • Author(s): Naito Y, Tsujino T, et al.
  • Journal Title: Rats. Clinical and Experimental Hypertension. 31 Pages: 625-38
  • Peer Reviewed
• [Journal Article] High salt intake elevated blood pressure but not changed circadian blood pressure rhythm in Otsuka Long-Evans Tokushima Fatty(OLETF)rat. (2009)
  • Author(s): Matsumoto M, Tsujino T, et al
  • Journal Title: Clin Exp Hypertens. 31 Pages: 271-80
  • Peer Reviewed
• [Journal Article] Adaptive response of the heart to long-term anemia induced by iron deficiency. (2009)
  • Author(s): Naito Y, Tsujino T, et al.
  • Journal Title: Am J Physiol Heart Circ Physiol. 296(3) Pages: 585-93
  • Peer Reviewed
• [Presentation] 鉄制限は2型糖尿病ラットの早期腎症を予防する (2012)
  • Author(s): 竹内志織、佐々木尚子、岡田侑磨、前田有貴、石田拓巳、松本実佳、増山理、辻野健
  • Organizer: 日本薬学会第132回年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-29
• [Presentation] 慢性腎臓病モデルにおける鉄の関与 (2011)
  • Author(s): 藤井彩, 内藤由朗, 澤田悠, 辻野健, 佐々木尚子, 赤堀宏州, 大柳光正, 増山理
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 栃木
• [Presentation] (Featured Research Session) Beta-blocker therapy may inhibit collagen degradation, and improve LV systolic function (2011)
  • Author(s): Yoshida C, Hirotani S, Goda A, Masaki M, Nakaboh A, Lee-Kawabata M, Tsujino T, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Statin use reduces neoangiogenesis and intraleaflet hemorrhage in the aortic valve of degenerative aortic stenosis (2011)
  • Author(s): Akahori H, Tsujino T, Naito Y, Yoshida C, Fujii K, Lee-Kawabata M, Sakoda T, Mitsuno M, Miyamoto Y, Ohyanagi M, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] The improvement in LV diastolic stiffness correlated with inhibition of collagen degradation following induction of beta-blocker therapy (2011)
  • Author(s): Yoshida C, Hirotani S, Goda A, Masaki M, Nakaboh A, Lee-Kawabata M, Tsujino T, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Altered expression of iron regulating system in heart failure model rats : a possible mechanism of anemia associated with heart failure (2011)
  • Author(s): Naito Y, Tsujino T, Sawada H, Eguchi A, Iwasaku T, Akahori H, Hirotani S, Ohyanagi M, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Effects of efonizipine, calcium channel blocker, on exercise tolerance and left ventricular diastolic function in patients with myocardial infarction (2011)
  • Author(s): Naka T, Yoshida C, Akagami T, Doi T, Takahashi K, Masutani M, Sakoda T, Tsujino T, Masuyama T, Ohyanagi M
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Addition of statin therapy to cardiac rehabilitation synergistically improves left ventricular diastolic function in patients with chronic heart failure (2011)
  • Author(s): Yoshida C, Hirotani S, Lee-Kawabata M, Goda A, Masaki M, Otsuka M, Nakaboh A, Eguchi A, Tsujino T, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Atorvastatin improves LV diastolic function in rat model of diastolic heart failure by lowering collagen-specific chaperone HSP47 (2011)
  • Author(s): Akahori H, Tsujino T, Naito Y, Matsumoto M, Eguchi A, Hirotani S, Lee-Kawabata M, Sakoda T, Ohyanagi M, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Impact of intravenous vasodilators on renal function in patients with acute cardiogenic pulmonary edema treated with carperitide or isosorbide dinitrate (2011)
  • Author(s): Fujii K, Iwasaku T, Doi T, Okumura T, Sawada H, Hirotani S, Lee-Kawabata M, Tsujino T, Ohyanagi M, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Duration of acute kidney injury and long-term clinical-events in patients with pre-existing renal dysfunction hospitalized for acute cardiogenic pulmonary edema (2011)
  • Author(s): Fujii K, Iwasaku T, Doi T, Okumura T, Sawada H, Hirotani S, Lee-Kawabata M, Tsujino T, Ohyanagi M, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Advanced glycation end products predict left ventricular chamber stiffness and remodeling in patients with non-diabetic hypertension (2011)
  • Author(s): Masaki M, Hirotani S, Goda A, Yoshida C, Nakaboh A, Ohtsuka M, Lee-Kawabata M, Tsujino T, Koshiba M, Yamagishi S, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Chaotic nature of myocardial ultrasonic radio frequency signals reflect inflammation and collagen production in patients with hypertension (2011)
  • Author(s): Masaki M, Goda A, Hirotani S, Yoshida C, Nakaboh A, Ohtsuka M, Lee-Kawabata M, Tsujino T, Koshiba M, Yamagishi S, Masuyama T
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] 慢性心不全患者の心臓リハビリテーションにスタテン治療を併用することの有用性 (2011)
  • Author(s): 中坊亜由美, 吉田千佳子, 廣谷信一, 合田亜希子, 正木充, 大塚美里, 大江良子, 江口明世, 澤田悠, 川端正明, 辻野健, 増山理
  • Organizer: 第22回日本心エコー図学会学術集会
  • Place of Presentation: 鹿児島
• [Presentation] 器質的心疾患を伴わない肺動脈圧上昇症例の症状と心機能との関係:心エコー図所見からみた特徴 (2011)
  • Author(s): 奥平久美子, 合田亜希子, 中坊亜由美, 正木充, 大塚美里, 吉田千佳子, 大江良子, 江口明世, 田中益水, 牧原佐知子, 三角千香, 西村純子, 吉本直喜, 松永桃子, 廣谷信一, 川端正明, 飯島尋子, 辻野健, 増山理
  • Organizer: 第22回日本心エコー図学会学術集会
  • Place of Presentation: 鹿児島
• [Presentation] β遮断薬導入による左室収縮能改善とコラーゲン代謝との関連 (2011)
  • Author(s): 大江良子, 吉田千佳子, 中坊亜由美, 合田亜希子, 正木充, 廣谷信一, 川端正明, 辻野健, 増山理
  • Organizer: 第22回日本心エコー図学会学術集会
  • Place of Presentation: 鹿児島
• [Presentation] 三尖弁逆流と動脈スティフネスとの関係 (2011)
  • Author(s): 正木充, 廣谷信一, 合田亜希子, 大江良子, 中坊亜由美, 吉田千佳子, 川崎大三, 川端正明, 辻野健, 小柴賢洋, 増山理
  • Organizer: 第22回日本心エコー図学会学術集会
  • Place of Presentation: 鹿児島
• [Presentation] 動脈スティフネスと左室拡張能の関連 (2011)
  • Author(s): 正木充, 廣谷信一, 合田亜希子, 大江良子, 中坊亜由美, 吉田千佳子, 川崎大三, 川端正明, 辻野健, 小柴賢洋, 増山理
  • Organizer: 第22回日本心エコー図学会学術集会
  • Place of Presentation: 鹿児島
• [Presentation] β遮断薬治療による左室スティフネスの改善はコラーゲン分解の抑制と関連する (2011)
  • Author(s): 大江良子, 吉田千佳子, 廣谷信一, 合田亜希子, 正木充, 中坊亜由美, 川端正明, 辻野健, 増山理
  • Organizer: 日本超音波医学会第84回学術集会
  • Place of Presentation: 東京
• [Presentation] 心リハにボルテゾミブ・デキサメサゾン療法を併用し運動能の改善が得られた心アミロイドーシスの1例 (2011)
  • Author(s): 中聡夫, 吉田千佳子, 赤神隆文, 土居隆, 中坊亜由美, 高橋敬子, 笹沼直樹, 山内真哉, 井谷祐介, 田中隆史, 佐古田剛, 辻野健, 増山理, 岡田昌也
  • Organizer: 第17回日本心臓リハビリテーション学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 大動脈弁狭窄症弁組織におけるBone morphogenetic protein-binding endothelial regulator (BMPER)発現 (2011)
  • Author(s): 澤田悠, 内藤由朗, 辻野健, 奥原祥貴, 江口明世, 岩破俊博, 赤堀宏州, 廣谷信一, 大柳光正, 光野正孝, 宮本裕治, 増山理
  • Organizer: 第59回日本心臓病学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 先天性2尖弁による大動脈弁狭窄症の組織学的検討:加齢変性に伴う3尖弁の大動脈弁狭窄症との比較 (2011)
  • Author(s): 赤堀宏州, 辻野健, 内藤由朗, 吉田千佳子, 佐々木尚子, 川端正明, 大柳光正, 光野正孝, 宮本裕治, 増山理
  • Organizer: 第59回日本心臓病学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 収縮不全心のβ遮断薬導入療法はコラーゲン分解を抑制し左室リモデリングを抑制する (2011)
  • Author(s): 吉田千佳子, 廣谷信一, 中坊亜由美, 合田亜希子, 正木充, 川端正明, 辻野健, 増山理
  • Organizer: 第59回日本心臓病学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 急性心筋梗塞患者に対するエホニジピン追加投与は心臓リハビリテーションの効果を増強する (2011)
  • Author(s): 中聡夫, 吉田千佳子, 赤神隆文, 土居隆, 辻野健, 増山理, 大柳光正
  • Organizer: 第15回日本心不全学会学術集会
  • Place of Presentation: 鹿児島
• [Presentation] アトロバスタチンによる心拡張能改善の機序 (2011)
  • Author(s): 赤堀宏州, 辻野健, 佐々木尚子, 内藤由朗, 松本実佳, 増山理
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 栃木
• [Presentation] Neoangiogenesis, intraleaflet haemorrhage and macrophage infiltration are more remarkable in bicuspid aortic valve stenosis than in tricuspid aortic valve stenosis (2011)
  • Author(s): Akahori H, Tsujino T, Naito Y, Yoshida C, Sasaki N, Lee-Kawabata M, Ohyanagi M, Mitsuno M, Miyamoto Y, Masuyama T
  • Organizer: European Society of Cardiology Congress 2011
  • Place of Presentation: France
• [Presentation] Statin use reduces neoangiogenesis and intraleaflet haemorrhage in the aortic valve of degenerative aortic stenosis (2011)
  • Author(s): Akahori H, Tsujino T, Naito Y, Yoshida C, Sasaki N, Lee-Kawabata M, Ohyanagi M, Mitsuno M, Miyamoto Y, Masuyama T
  • Organizer: European Society of Cardiology Congress 2011
  • Place of Presentation: France
• [Presentation] The correlation between collagen degradation and LV function following inducation of beta blocker therapy (2011)
  • Author(s): Yoshida C, Masaki M, Hirotani S, Goda A, Otsuka M, Nakaboh A, Eguchi A, Lee-Kawabata M, Tsujino T, Masuyama T
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: USA
• [Presentation] 鉄制限は2型糖尿病モデルラットの早期腎症発症を予防する (2010)
  • Author(s): 佐々木尚子, 松本実佳, 内藤由朗, 赤堀宏州, 増山理, 辻野健
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
• [Presentation] 大動脈弁狭窄症進行における弁尖内出血の意義 (2010)
  • Author(s): 辻野健
  • Organizer: 第83回日本超音波医学会学術集会2010
  • Place of Presentation: 京都
• [Presentation] 心不全患者におけるへプシジンの動態. (2009)
  • Author(s): 辻野健
  • Organizer: 第33回鉄バイオサイエンス学会学術集会2009
  • Place of Presentation: 倉敷
  • Year and Date: 2009-09-12
• [Book] 循環器疾患と薬物治療. (2009)
  • Author(s): 辻野健
  • Total Pages: 510
  • Publisher: 薬物治療学(平井みどり,三木知博編),化学同人,京都,55-110,2009.