研究者詳細 - 森松　博史

MISC - 森松　博史

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Role of heme oxygenase-1 in protection of the kidney after hemorrhagic shock

Yutaka Arimori, Toru Takahashi, Hiroyuki Nishie, Kazuyoshi Inoue, Hiroko Shimizu, Emiko Omori, Susumu Kawanishi, Yuichiro Toda, Hiroshi Morimatsu, Kiyoshi Morita

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 26 ( 1 ) 27 - 32 2010年7月

記述言語：英語出版者・発行元：SPANDIDOS PUBL LTD

Hemorrhagic shock followed by resuscitation (HSR) causes oxidative stress, which results in multiple organ damage. The kidney is one of the target organs of HSR-mediated oxidative tissue injury. Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, is induced by oxidative stress; it protects against oxidative tissue injuries. The aim of the present study was to examine the role of renal HO-1 induction after HSR. Rats were subjected to hemorrhagic shock to achieve a mean arterial pressure of 30 mmHg for 60 min, followed by resuscitation with the shed blood. HSR resulted in a significant increase in functional HO-1 protein in the tubular epithelial cells of the kidney, whereas HSR resulted in only a slight increase in gene expression of tumor necrosis factor (TNE)-alpha and inducible nitric oxide synthase (iNOS), and in protein expression of activated caspase-3 solely in renal cells where HO-1 expression was absent. HSR also resulted in a significant increase in Bcl-2 gene expression. Pretreatment of HSR animals with tin-mesoporphyrin (0.5 mu mol/kg), a specific competitive inhibitor of HO activity, resulted in a significant decrease in HO activity and exacerbated tissue inflammation and apoptotic cell death as judged by the marked increase in expression of TNF-alpha and iNOS, and in activated caspase-3-positive cells, and the significant reduction in Bcl-2 expression, respectively. These findings indicate that HO-1 induction is an adaptive response to HSR-induced oxidative stress and is essential for protecting tubular epithelial cells from oxidative damage through its anti-inflammatory and anti-apoptotic properties.

DOI： 10.3892/ijmm_00000430

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肝切除術後鎮痛の検討:生体肝移植ドナーと腫瘍による肝切除患者の比較

塩崎恭子, 松崎孝, 中村龍, 中塚秀輝, 森松博史, 佐藤哲文, 溝渕知司, 森田潔

日本ペインクリニック学会誌 17 ( 2 ) 185 2010年5月

Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness

Sean M. Bagshaw, Michael Bennett, Michael Haase, Anja Haase-Fielitz, Moritoki Egi, Hiroshi Morimatsu, Giuseppe D'amico, Donna Goldsmith, Prasad Devarajan, Rinaldo Bellomo

INTENSIVE CARE MEDICINE 36 ( 3 ) 452 - 461 2010年3月

記述言語：英語出版者・発行元：SPRINGER

Sepsis is the most common trigger for acute kidney injury (AKI) in critically ill patients. We sought to determine whether there are unique patterns to plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in septic compared with non-septic AKI.
Prospective observational study.
Two adult ICUs in Melbourne, Australia.
Critically ill patients with septic and non-septic AKI.
None.
Blood and urine specimens collected at enrollment, 12, 24 and 48 h to measure plasma and urine NGAL. Eighty-three patients were enrolled (septic n = 43). Septic AKI patients had more co-morbid disease (p = 0.005), emergency surgical admissions (p < 0.001), higher illness severity (p = 0.008), more organ dysfunction (p = 0.008) and higher white blood cell counts (p = 0.01). There were no differences at enrollment between groups in AKI severity. Septic AKI was associated with significantly higher plasma (293 vs. 166 ng/ml) and urine (204 vs. 39 ng/mg creatinine) NGAL at enrollment compared with non-septic AKI (p < 0.001). Urine NGAL remained higher in septic compared with non-septic AKI at 12 h (p < 0.001) and 24 h (p < 0.001). Plasma NGAL showed fair discrimination for AKI progression (area under receiver-operator characteristic curve 0.71) and renal replacement therapy (AuROC 0.78). Although urine NGAL performed less well (AuROC 0.70, 0.70), peak urine NGAL predicted AKI progression better in non-septic AKI (AuROC 0.82).
Septic AKI patients have higher detectable plasma and urine NGAL compared with non-septic AKI patients. These differences in NGAL values in septic AKI may have diagnostic and clinical relevance as well as pathogenetic implications.

DOI： 10.1007/s00134-009-1724-9

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Serious Adverse Events(SAEs)と術中輸液管理の関係

塩崎恭子, 森松博史, 中村龍, 横山正尚, 中塚秀輝, 佐藤健治, 片山浩, 森田潔

日本集中治療医学会雑誌 17 ( Supplement ) 374 2010年1月

大学病院における高度侵襲手術後のSerious Adverse Events(SAEs)

森松博史, 横山正尚, 中塚秀輝, 中村龍, 塩崎恭子, 佐藤健治, 森田潔

日本集中治療医学会雑誌 17 ( Supplement ) 252 2010年1月

大動脈弁置換術中の大動脈遮断解除直後に発生した難治性心室細動に対して塩酸アミオダロン静脈内投与が奏効した1症例

鈴木聡, 岩崎達雄, 森松博史, 横井渚, 松岡舞夕子, 末盛智彦, 金澤伴幸, 清水一好, 戸田雄一郎, 森田潔

麻酔 59 ( 10 ) 1266 - 1270 2010年

記述言語：日本語出版者・発行元：克誠堂出版(株)

66歳男。労作時呼吸困難が持続し、高度大動脈弁狭窄症の診断で大動脈弁置換術が予定された。手術開始から大きな問題なく人工心肺開始、大動脈遮断となり、術操作も問題なく終了し、大動脈遮断時間は95分であった。遮断解除後に心室細動(VF)を認め、計3回の直流除細動器による電気ショックを行ったが改善せず、更に塩酸リドカインと硫酸マグネシウム液の静脈内投与後に計7回、次いで塩酸ニフェカラント投与後に計5回の電気ショックを行ったがVFは継続した。そこで、塩酸アミオダロンを静脈投与した後に電気ショックを行ったところ、1回で除細動に成功した。VFの持続時間は60分で、この間血液ガス分析では電解質や酸塩基平衡の異常はなかった。その後は心室ペーシング下で人工心肺を離脱し、手術終了となった。術後は塩酸アミオダロン、塩酸ランジオロールの静脈内持続投与を行い、VFの再発はなく、4日目に中止した。術後13日目にICUを退室し、63日目に退院した。

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骨髄移植後呼吸不全に陥った重症Veno-Occlusive Diseaseの小児症例

横井渚, 戸田雄一郎, 森松博史, 松﨑孝, 鈴木聡, 江木盛時, 片山浩, 森田潔

ＩＣＵとＣＣＵ 34 ( 11 ) 1007 - 1011 2010年

集中治療室での先天性心疾患におけるベクロニウム持続投与挿管時間との関係

清水一好, 森松博史, 戸田雄一郎, 鈴木聡, 金澤伴幸, 末盛智彦, 岩崎達雄, 森田潔

日本集中治療医学会雑誌 17 ( 3 ) 353 - 354 2010年

記述言語：日本語出版者・発行元：(一社)日本集中治療医学会

2006年12月〜2007年6月に、ICU入室後に筋弛緩薬を持続投与された先天性心疾患40例(6.3〜15.8ヵ月・平均11ヵ月)を対象に、挿管時間への影響因子について検討した。40例のうち37例(92.5%)は心臓手術後患者で、施行術式はRACHS-1カテゴリーで2.8〜3.6(平均3.2)、人工心肺時間92〜140分(平均116分)、大動脈遮断時間49〜82分(平均65分)、人工心肺中の冷却温度は24.8〜28.4℃(平均26.6℃)であった。ICU入室中に投与したベクロニウムの総投与量は3.3〜11.7mg・kg-1(平均7.5mg・kg-1)、持続投与中止から抜管までの時間は48.4〜153.9時間(平均101.1時間)と4日間を要していた。そのうち約80%の症例は100時間以内に抜管可能であった。5例は抜管まで200時間以上と長時間を要した。挿管時間と各因子の比例ハザードモデルによる単変量解析の結果、ベクロニウム総投与量と人工心肺冷却温度が有意に独立した危険因子であった。

DOI： 10.3918/jsicm.17.353

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【集中治療とMET(Medical Emergency Team)/RRT(Rapid Response Team)】諸外国での現状

森松博史, 塩崎恭子, 中村龍, 森田潔

ＩＣＵとＣＣＵ 34 ( 6 ) 447 - 452 2010年

【CRRT】開始・中止のタイミング

森松博史

Intensivist 2 ( 2 ) 257 - 262 2010年

【CRRT】 PMX-EUPHAS studyについて考える

森松博史

Intensivist 2 ( 2 ) 395 - 397 2010年

グルタミンはHo-1誘導を介して自然免疫系の活性化を抑制し出血性ショック後の腸管障害を軽減する

高橋徹, 井上一由, 清水裕子, 楳田佳奈, 有森豊, 川西進, 松三昌樹, 片山浩, 森松博史, 森田潔

エンドトキシン研究 10 65 - 68 2010年

LOW ANTITHROMBIN III LEVEL AND MORTALITY IN CRITICALLY ILL PATIENTS

Shiho Takenouchi, Moritoki Egi, Hiroshi Morimatsu, Yuichiro Toda, Kazuyoshi Shimizu, Kiyoshi Morita

CRITICAL CARE MEDICINE 37 ( 12 ) A126 - A126 2009年12月

ALTERATIONS OF PITUITARY HORMONES AFTER PEDIATRIC CARDIAC SURGERY

Kazuyoshi Shimizu, Hiroshi Morimatsu, Yuichiro Toda, Moritoki Egi, Tomohiko Suemori, Satoshi Suzuki, Tatsuo Iwasaki, Kiyoshi Morita

CRITICAL CARE MEDICINE 37 ( 12 ) A113 - A113 2009年12月

PERIOPERATIVE GLUCOSE VARIABILITY AND OXIDATIVE STRESS IN CARDIAC SURGERY PATIENTS

Moritoki Egi, Kazuyoshi Shimizu, Yuichiro Toda, Tatsuo Iwasaki, Hiroshi Morimatsu, Kiyoshi Morita

CRITICAL CARE MEDICINE 37 ( 12 ) A112 - A112 2009年12月

Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study

Shigehiko Uchino, Rinaldo Bellomo, Hiroshi Morimatsu, Stanislao Morgera, Miet Schetz, Ian Tan, Catherine Bouman, Ettiene Macedo, Noel Gibney, Ashita Tolwani, Heleen Oudemans-van Straaten, Claudio Ronco, John A. Kellum

CRITICAL CARE MEDICINE 37 ( 9 ) 2576 - 2582 2009年9月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Objectives: To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes. However, there is lack of information on how and under what conditions continuous renal replacement therapy is discontinued.
Design: Post hoc analysis of a prospective observational study.
Setting. Fifty-four intensive care units in 23 countries.
Patients: Five hundred twenty-nine patients (52.6%) who survived initial therapy among 1006 patients treated with continuous renal replacement therapy.
Interventions: None.
Measurements and Main Results., Three hundred thirteen patients were removed successfully from continuous renal replacement therapy and did not require any renal replacement therapy for at least 7 days and were classified as the "success" group and the rest (216 patients) were classified as the "repeat-RRT" (renal replacement therapy) group. Patients in the "success" group had lower hospital mortality (28.5% vs. 42.7%, p < .0001) compared with patients in the "repeat-RRT" group. They also had lower creatinine and urea concentrations and a higher urine output at the time of stopping continuous renal replacement therapy. Multivariate logistic regression analysis for successful discontinuation of continuous renal replacement therapy identified urine output (during the 24 hrs before stopping continuous renal replacement therapy: odds ratio, 1.078 per 100 mL/day increase) and creatinine (odds ratio, 0.996 per mu mol/L increase) as significant predictors of successful cessation. The area under the receiver operating characteristic curve to predict successful discontinuation of continuous renal replacement therapy was 0.808 for urine output and 0.635 for creatinine. The predictive ability of urine output was negatively affected by the use of diuretics (area under the receiver operating characteristic curve, 0.671 with diuretics and 0.845 without diuretics).
Conclusions. We report on the current practice of discontinuing continuous renal replacement therapy in a multinational setting. Urine output at the time of initial cessation (if continuous renal replacement therapy was the most important predictor of successful discontinuation, especially if occurring without the administration of diuretics. (Crit Care Med 2009; 37:2576-2582)

DOI： 10.1097/CCM.0b013e3181a38241

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肝切除術後鎮痛の検討:静脈内PCA法と硬膜外PCEA法の比較

塩崎恭子, 松崎孝, 梶原秀年, 溝渕知司, 佐藤哲文, 森松博史, 中塚秀輝, 西江宏行, 佐藤健治, 森田潔

日本ペインクリニック学会誌 16 ( 3 ) 430 2009年6月

Non-overt disseminated intravascular coagulation scoring for critically ill patients: The impact of antithrombin levels

Moritoki Egi, Hiroshi Morimatsu, Christian J. Wiedermann, Makiko Tani, Tomoyuki Kanazawa, Satoshi Suzuki, Takashi Matsusaki, Kazuyoshi Shimizu, Yuichiro Toda, Tatsuo Iwasaki, Kiyoshi Morita

THROMBOSIS AND HAEMOSTASIS 101 ( 4 ) 696 - 705 2009年4月

記述言語：英語出版者・発行元：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN

Validation of a scoring algorithm for non-overt disseminated intravascular coagulation (DIC) proposed by the International Society on Thrombosis and Haemostasis (ISTH) is still incomplete. It was the objective of this study to assess the impact of including AT to non-overt DIC scoring on the predictability for intensive care unit (ICU) death and the later development of overt-DIC defined by the Japanese Ministry of Health and Welfare (JMHW) or the ISTH. We performed a retrospective observational study conducted in 364 patients in critical care. Coagulation parameters obtained daily for DIC screening were utilised for scoring. There were 194 and 196 patients scored as positive non-overt DIC with and without AT, respectively; diagnostic agreement between the two was 78%. As compared with patients without non-overt DIC, these non-overt DIC patients had significantly higher mortality. In 37 ICU non-survivors, positive non-overt DIC scoring with AT preceded ICU death by a median of 6.8 days, which was significantly earlier as compared with a median of 5.4 days for non-overt DIC without AT (p=0.022). In patients who developed overt-DIC after admission, the time period from positive non-overt DIC to positive overt-DIC was significantly longer when AT was utilised (overt-DIC ISTH; 1.3 days vs. 0.1 days, p=0.004, overt-DIC JMHW; 2.5 days vs. 2.0 days, p=0.04, with AT vs. without AT, respectively). Non-overt DIC scoring predicted a high risk of death in critically ill patients. When information on AT levels was included, non-overt DIC scoring was found to predict development of overt-DIC significantly earlier than non-overt DIC scoring without AT.

DOI： 10.1160/TH08-07-0448

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Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury

Sean M. Bagshaw, Shigehiko Uchino, Rinaldo Bellomo, Hiroshi Morimatsu, Stanislao Morgera, Miet Schetz, Ian Tan, Catherine Bouman, Ettiene Macedo, Noel Gibney, Ashita Tolwani, Heleen M. Oudemans-van Straaten, Claudio Ronco, John A. Kellum

JOURNAL OF CRITICAL CARE 24 ( 1 ) 129 - 140 2009年3月

記述言語：英語出版者・発行元：W B SAUNDERS CO-ELSEVIER INC

Purpose: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes.
Methods: This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients.
Results: Timing of RRT was stratified into "early" and "late" by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early (<2 days), delayed (2-5 days), and late (>5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea <= 24.2 mmol/L vs 61.4% for urea >24.2 mmol/L; odds ratio [OR], 0.92; 95% confidence interval [CI], 0.73-1.15; P = .48) or covariate-adjusted mortality (OR, 1.25; 95% CI, 0.91-1.70; P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine >309 mu mol/L vs 71.4% for creatinine <= 309 mu mol/L; OR, 0.46; 95% CI, 0.36-0.58; P < .0001) and covariate-adjusted mortality (OR, 0.51; 95% CI, 0.37-0.69; P < .001).However, for timing relative to ICU admission, late RRT was associated with greater crude (72.8% vs 62.3% vs 59%, P < .001) and covariate-adjusted mortality (OR, 1.95; 95% CI, 1.30-2.92; P = .001). Overall, late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence.
Conclusion: Timing of RRT, a potentially modifiable factor, might exert an important influence on patient survival. However, this largely depended on its definition. Late RRT (days from admission) was associated with a longer duration of RRT, longer hospital stay, and higher dialysis dependence. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jcrc.2007.12.017

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PREVENTION OF HEMORRHAGIC SHOCK-INDUCED INTESTINAL TISSUE INJURY BY GLUTAMINE VIA HEME OXYGENASE-1 INDUCTION

Kana Umeda, Toru Takahashi, Kazuyoshi Inoue, Hiroko Shimizu, Shigeru Maeda, Hiroshi Morimatsu, Emiko Omori, Reiko Akagi, Hiroshi Katayama, Kiyoshi Morita

SHOCK 31 ( 1 ) 40 - 49 2009年1月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Hemorrhagic shock (HS) is an oxidative stress that causes intestinal tissue injury. Heme oxygenase 1 (HO-1) is induced by oxidative stress and is thought to play an important role in the protection of tissues from oxidative injury. We previously reported the ileum to be the most susceptible to HS-induced tissue injury site in the intestine because HO-1 induction is the lowest at this site. We also previously demonstrated that glutamine (GLN) significantly induced HO-1 in the lower intestinal tract. In the present study, we investigated whether GLN pretreatment improves HS-induced intestinal tissue injury in the ileum by HO-1 induction. Treatment of rats with GLN (0.75 g/kg, i.v.) markedly induced functional HO-1 protein in mucosal epithelial cells in the ileum. Glutamine treatment before HS (MAP of 30 mmHg for 60 min) significantly ameliorated HS-induced mucosal inflammation and apoptotic cell death in the ileum, as judged by significant decreases in gene expression of TNF-alpha, iNOS, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1, myeloperoxidase activity, the number of infiltrated neutrophils, DNA fragmentation by in situ oligo ligation assay, and activated caspase-3 expression, and by increases in gene expression of IL-10 and Bcl-2. In contrast, treatment with tin mesoporphyrin, a specific inhibitor of HO activity, abolished the beneficial effect of GLN pretreatment. These findings indicate that GLN pretreatment significantly ameliorated tissue injury in the ileum after HS by inducing HO-1. Glutamine treatment may thus protect mucosal cells from HS-induced oxidative damage via the anti-inflammatory and antiapoptotic properties of HO-1.

DOI： 10.1097/SHK.0b013e318177823a

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