Papers - OHTAKE Kazuo
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ベイズ型age-period-cohort分析を用いた日本の予測平均余命の性差(2023～2047年) Reviewed
内田 博之, 三藤 瑠莉, 瓶子 英朗, 斎藤 雅文, 小田切 陽一, 大竹 一男, 八巻 努, 内田 昌希, 夏目 秀視, 小林 順
日本衛生学雑誌 73 ( 3 ) 338 - 353 2018.09
Language：Japanese Publisher：(一社)日本衛生学会
日本の1958～2012年までの全死因および主要死因別の性別年齢階級別死亡数は人口動態統計、1958～2012年までの性別年齢階級別人口は国勢調査報告および10月1日現在推計人口、2013～2047年までの日本の性別年齢階級別将来推計人口は国立社会保障・人口問題研究所より得た。1958～1962年から2008～2012年にかけて男女ともすべての年齢階級別死亡率は低下傾向を示し、特に15歳未満でその傾向が大きかった。出生年次別の死亡率は、男女ともすべての年齢階級で出生年の推移に伴い低下傾向を示し、特に20歳未満の傾きが大きかった。全死因の死亡率の年次推移に対する年齢効果、時代効果およびコホート効果の推計値の比較より、死亡率の年次推移は、男女ともに年齢効果が一番大きく影響し、男性でコホート効果の次に時代効果、女性で時代効果の次にコホート効果が影響した。平均余命の将来予測では、2008～2012年から2043～2047年までの期間に、0～4歳の平均余命は2023～2027年に一端短縮するものの男性が1.64年、女性が0.70年延伸し、他の年齢階級においても同様に平均余命の延伸が予測された。
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Improved Intranasal Retentivity and Transnasal Absorption Enhancement by PEGylated Poly-l-ornithine. Reviewed International journal
Yusuke Kamiya, Tsutomu Yamaki, Shigehiro Omori, Masaki Uchida, Kazuo Ohtake, Mitsutoshi Kimura, Hiroshi Yamazaki, Hideshi Natsume
Pharmaceuticals (Basel, Switzerland) 11 ( 1 ) 2018.01
Language：English Publishing type：Research paper (scientific journal)
We reported that the introduction of polyethylene glycol (PEG) to poly-l-ornithine (PLO), which is an homopolymeric basic amino acid having absorption-enhancement ability, prolonged retention time in an in vitro inclined plate test, probably due to an increase in viscosity caused by PEGylation. The aim of the present study is to investigate whether the introduction of PEG chains to PLO improves intranasal retention and transnasal absorption in vivo. We performed intranasal administration experiments using PLO and PEG-PLO with a model drug, fluorescein isothiocyanate dextran (FD-4), in rats under closed and open systems. In the open system, transition of plasma FD-4 concentration after co-administration with unmodified PLO was low, and the area under the plasma concentration-time curve (AUC) decreased to about 60% of that in the closed system. In contrast, the AUC after co-administration with PEG-PLO in the open system was about 90% of that in the closed system, and the transition of plasma FD-4 concentration and FD-4 absorption profile were similar to those of the closed system. These findings indicate that introducing PEG chains to homopolymeric basic amino acids (HPBAAs) is a very useful method for developing a functional absorption enhancer that can exhibit an efficient in vivo absorption-enhancing effect.
DOI： 10.3390/ph11010009
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Hiroyuki Uchida, Ruri Mito, Hideaki Heishi, Masafumi Saito, Youichi Odagiri, Kazuo Ohtake, Tutomu Yamaki, Masaki Uchida, Hideshi Natsume, Jun Kobayashi
Nihon eiseigaku zasshi. Japanese journal of hygiene 73 ( 3 ) 338 - 353 2018
Language：Japanese Publishing type：Research paper (scientific journal)
OBJECTIVES: In this study, we aimed to (1) determine the effects of age, period, and cohort on mortality rate trends between 1958 and 2012 in Japan and (2) assess gender differences in projected life expectancy (LE) for the 2023-2047 period. METHODS: A time trend study was conducted using age-period-cohort (APC) analysis. A Bayesian APC model was fitted to describe mortality rate trends for the 1958-2012 period and to project mortality rates for 2023-2047. LE was predicted by Chiang's method using projected mortality rates. RESULTS: Age, period, and cohort effects showed similar patterns between males and females. As time passes, gender differences in projected LE were larger among individuals over 65 years than among those under 65 years. Time series change rates of the extension of projected LE after excluding specific causes of death showed the following: smaller extension of projected LE in males in terms of mortality risk from malignant neoplasms, heart diseases, pneumonia, and accidents (under 65 years) and in females in terms of mortality risk from heart diseases, cerebrovascular diseases, and suicide (over 65 years). CONCLUSIONS: Gender differences in projected LE are expected to be smaller before middle age and to be larger among seniors. These projected gender differences stem in part from the lower mortality risk among men than among women from malignant neoplasms, heart diseases, pneumonia, and accidents (under 65 years), and among women compared to men from heart disease, cerebrovascular disease, and suicide (over 65 years).
DOI： 10.1265/jjh.73.338
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Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress Reviewed International journal
Hiroyuki Uchida, Yukari Nakajima, Kazuo Ohtake, Junta Ito, Masahiko Morita, Ayako Kamimura, Jun Kobayashi
WORLD JOURNAL OF GASTROENTEROLOGY 23 ( 36 ) 6650 - 6664 2017.09
Language：English Publishing type：Research paper (scientific journal) Publisher：BAISHIDENG PUBLISHING GROUP INC
AIM
To determine whether oral glutathione (GSH) administration can alleviate the effects of fasting-induced intestinal atrophy in the small intestinal mucosa.
METHODS
Rats were divided into eight groups. One group was fed ad libitum, another was fed ad libitum and received oral GSH, and six groups were administrated saline (SA) or GSH orally during fasting. Mucosal height, apoptosis, and cell proliferation in the jejunum were histologically evaluated. iNOS protein expression (by immunohistochemistry), nitrite levels (by high performance liquid chromatography, as a measure of NO production), 8-hydroxydeoxyguanosine formation (by ELISA, indicating ROS levels), glutathione/ oxidized glutathione (GSH/GSSG) ratio (by enzymatic colorimetric detection), and gamma-glutamyl transpeptidase (Ggt1) mRNA levels in the jejunum (by semi-quantitative RT-PCR) were also estimated.
RESULTS
Oral GSH administration was demonstrated to drastically reduce fasting-induced intestinal atrophy in the jejunum. In particular, jejunal mucosal height was enhanced in GSH-treated animals compared to SA-treated animals [527.2 +/- 6.9 for 50 mg/kg GSH, 567.6 +/- 5.4 for 500 mg/kg GSH vs 483.1 +/- 4.9 (mu m), P < 0.01 at 72 h]. This effect was consistent with decreasing changes in GSH-treated animals compared to SA-treated animals for iNOS protein staining [0.337 +/- 0.016 for 50 mg/kg GSH, 0.317 +/- 0.017 for 500 mg/kg GSH vs 0.430 +/- 0.023 (area of staining part/area of tissue), P < 0.01 at 72 h] and NO [2.99 +/- 0.29 for 50 mg/kg GSH, 2.88 +/- 0.19 for 500 mg/kg GSH vs 5.34 +/- 0.35 (nmol/g tissue), P < 0.01 at 72 h] and ROS [3.92 +/- 0.46 for 50 mg/kg GSH, 4.58 +/- 0.29 for 500 mg/kg GSH vs 6.42 +/- 0.52 (8-OHdG pg/mu g DNA), P < 0.01, P < 0.05 at 72 h, respectively] levels as apoptosis mediators in the jejunum. Furthermore, oral GSH administration attenuated cell proliferation decreases in the fasting jejunum [182.5 +/- 1.9 for 500 mg/kg GSH vs 155.8 +/- 3.4 (5-BrdU positive cells/10 crypts), P < 0.01 at 72 h]. Notably, both GSH concentration and Ggt1 mRNA expression in the jejunum were also attenuated in rats following oral administration of GSH during fasting as compared with fasting alone [0.45 +/- 0.12 vs 0.97 +/- 0.06 (nmol/mg tissue), P < 0.01; 1.01 +/- 0.11 vs 2.79 +/- 0.39 (Ggt1 mRNA/Gapdh mRNA), P < 0.01 for 500 mg/kg GSH at 48 h, respectively].
CONCLUSION
Oral GSH administration during fasting enhances jejunal regenerative potential to minimize intestinal mucosal atrophy by diminishing fasting-mediated ROS generation and enterocyte apoptosis and enhancing cell proliferation. -
Inducible and neuronal nitric oxide synthases exert contrasting effects during rat intestinal recovery following fasting Reviewed International journal
Junta Ito, Hiroyuki Uchida, Naomi Machida, Kazuo Ohtake, Yuki Saito, Jun Kobayashi
EXPERIMENTAL BIOLOGY AND MEDICINE 242 ( 7 ) 762 - 772 2017.04
Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE PUBLICATIONS LTD
We investigated the effects of endogenous inducible (iNOS) and neuronal nitric oxide synthase on recovery from intestinal mucosal atrophy caused by fasting-induced apoptosis and decreased cell proliferation during refeeding in rats. Rats were divided into five groups, one of which was fed ad libitum, and four of which underwent 72h of fasting, followed by refeeding for 0, 6, 24, and 48 h, respectively. iNOS and neuronal nitric oxide synthase mRNA and protein levels in jejunal tissues were measured, and mucosal height was histologically evaluated. Apoptotic indices, interferon-gamma (IFN-gamma) transcription levels, nitrite levels (as a measure of nitric oxide [NO] production),8-hydroxydeoxyguanosine formation (indicating reactive oxygen species [ROS] levels), crypt cell proliferation, and the motility indices (MI) were also estimated. Associations between mucosal height and NOS protein levels were determined using Spearman's rank correlation test. Notably, we observed significant increases in mucosal height and in neuronal nitric oxide synthase mRNA and protein expression as refeeding time increased. Indeed, there was a significant positive correlation between neuronal nitric oxide synthase protein level and mucosal height during the 48-h refeeding period (r=0.725, P<0.01). Conversely, iNOS mRNA and protein expression decreased according to refeeding time, with a significant negative correlation between iNOS protein level and mucosal height being recorded during the 48-h refeeding period (r=-0.898, P<0.01). We also noted a significant negative correlation between jejunal neuronal nitric oxide synthase and iNOS protein concentrations over this same period (r=-0.734, P<0.01). Refeeding also restored the decreased jejunal MI caused by fasting. Our finding suggests that refeeding likely repairs fasting-induced jejunal atrophy by suppressing iNOS expression and subsequently inhibiting NO, ROS, and IFN- as apoptosis mediators, and by promoting neuronal nitric oxide synthase production and inducing crypt cell proliferation via mechanical stimulation.
Impact statement
Besides providing new data confirming the involvement of iNOS and nNOS in intestinal mucosal atrophy caused by fasting, this study details their expression and function during recovery from this condition following refeeding. We demonstrate a significant negative correlation between iNOS and nNOS levels during refeeding, and associate this with cell proliferation and apoptosis in crypts and villi. These novel findings elucidate the relationship between these NOS isoforms and its impact on recovery from intestinal injury. A mechanism is proposed comprising the up-regulation of nNOS activity by mechanical stimulation due to the presence of food in the intestine, restricting iNOS-associated apoptosis and promoting cell proliferation and gut motility. Our investigation sheds light on the molecular basis behind the repercussions of total parenteral nutrition on intestinal mucosal integrity, and more importantly, the beneficial effects of early enteral feeding. -
Identification of the cysteine residue responsible for oxidative inactivation of mouse galectin-2. Reviewed International journal
Mayumi Tamura, Akari Sasai, Rika Ozawa, Masanori Saito, Kaori Yamamoto, Tomoharu Takeuchi, Kazuo Ohtake, Hiroaki Tateno, Jun Hirabayashi, Jun Kobayashi, Yoichiro Arata
Journal of biochemistry 160 ( 4 ) 233 - 241 2016.10
Language：English Publishing type：Research paper (scientific journal)
Galectins are a group of animal lectins characterized by their specificity for β-galactosides. Mouse galectin-2 (mGal-2) is predominantly expressed in the gastrointestinal tract and has been identified as one of the main gastric mucosal proteins that are uniquely sensitive to S-nitrosylation. We have previously reported that oxidation of mGal-2 by hydrogen peroxide (H2O2) resulted in the loss of sugar-binding ability, whereas pre-treatment of mGal-2 with S-nitrosocysteine prevented H2O2-induced inactivation. In this study, we used point-mutated recombinant mGal-2 proteins to study which of the two highly conserved Cys residues in mGal-2 must be S-nitrosylated for protection against oxidative inactivation. Mutation of Cys57 to a Met residue (C57M) did not result in lectin inactivation following H2O2 treatment, whereas Cys75 mutation to Ser (C75S) led to significantly reduced lectin activity, as is the case for wild-type mGal-2. However, pre-treatment of the C75S mutant with S-nitrosocysteine protected the protein from H2O2-induced inactivation. Therefore, Cys57 is suggested to be responsible for oxidative inactivation of the mGal-2 protein, and protection of the sulfhydryl group of the Cys57 in mGal-2 by S-nitrosylation is likely important for maintaining mGal-2 protein function in an oxidative environment such as the gastrointestinal tract.
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Development of a Transnasal Delivery System for Recombinant Human Growth Hormone (rhGH): Effects of the Concentration and Molecular Weight of Poly-L-arginine on the Nasal Absorption of rhGH in Rats Reviewed
Ryo Kawashima, Masaki Uchida, Tsutomu Yamaki, Kazuo Ohtake, Tomomi Hatanaka, Hiroyuki Uchida, Hideo Ueda, Jun Kobayashi, Yasunori Morimoto, Hideshi Natsumea
BIOLOGICAL & PHARMACEUTICAL BULLETIN 39 ( 3 ) 329 - 335 2016.03
Language：English Publishing type：Research paper (scientific journal) Publisher：PHARMACEUTICAL SOC JAPAN
A novel system for delivering recombinant human growth hormone (rhGH) that is noninvasive and has a simple method of administration is strongly desired to improve the compliance of children. The aim of this study was to investigate the potential for the intranasal (i.n.) co-administration of rhGH with poly-L-arginine (PLA) as a novel delivery system by evaluating the effects of the concentration and molecular weight of PLA on the nasal absorption of rhGH. The influence of the formation of insoluble aggregates and a soluble complex in the dosage formulation on nasal rhGH absorption was also evaluated by size-exclusion chromatography and ultrafiltration. PLA enhanced the nasal absorption of rhGH at each concentration and molecular weight examined. Nasal rhGH absorption increased dramatically when the PLA concentration was 1.0 % (w/v) due to the improved solubility of rhGH in the formulation. A delay in rhGH absorption was observed when the molecular weight of PLA was increased. This appeared to be because the increase in molecular weight caused the formation of a soluble complex. It seems that the PLA concentration affects the absorption-enhancing effect on rhGH, while the molecular weight of PLA affects the time when the maximum plasma rhGH concentration was reached (T-max) of rhGH after i.n. administration, mainly because of the interactions among rhGH, PLA, and additives. Therefore, the transnasal rhGH delivery system using PLA is considered to be a promising alternative to subcutaneous (s.c.) injection if these interactions are sufficiently controlled.
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大学男子駅伝選手の常圧下低酸素環境を利用したトレーニングにおける魚油製剤摂取の効果 Reviewed
櫛部 静二, 小林 悟, 竹之内 康広, 金 賢珠, 新井 尚之, 野部 浩司, 大竹 一男, 白幡 晶, 加園 恵三
脂質栄養学 25 ( 1 ) 61 - 74 2016.03
Language：Japanese Publisher：日本脂質栄養学会
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Identification of the cysteine residue responsible for oxidative inactivation of mouse galectin-2. Reviewed International journal
Tamura M, Sasai A, Ozawa R, Saito M, Yamamoto K, Takeuchi T, Ohtake K, Tateno H, Hirabayashi J, Kobayashi J, Arata Y.
J Biochem. 160 233 - 241 2016
Language：English Publishing type：Research paper (scientific journal)
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S-nitrosylation of mouse galectin-2 prevents oxidative inactivation by hydrogen peroxide. Reviewed International journal
Mayumi Tamura, Masanori Saito, Kaori Yamamoto, Tomoharu Takeuchi, Kazuo Ohtake, Hiroaki Tateno, Jun Hirabayashi, Jun Kobayashi, Yoichiro Arata
Biochemical and biophysical research communications 457 ( 4 ) 712 - 7 2015.02
Language：English Publishing type：Research paper (scientific journal)
Galectins are a group of animal lectins characterized by their specificity for β-galactosides. Galectin-2 (Gal-2) is predominantly expressed in the gastrointestinal tract. A proteomic analysis identified Gal-2 as a protein that was S-nitrosylated when mouse gastric mucosal lysates were reacted with S-nitrosoglutathione, a physiologically relevant S-nitrosylating agent. In the present study, recombinant mouse (m)Gal-2 was S-nitrosylated using nitrosocysteine (CysNO), which had no effect on the sugar-binding specificity and dimerization capacity of the protein. On the other hand, mGal-2 oxidation by H2O2 resulted in the loss of sugar-binding ability, while S-nitrosylation prevented H2O2-inducted inactivation, presumably by protecting the Cys residue(s) in the protein. These results suggest that S-nitrosylation by nitric oxides protect Gal-2 from oxidative stress in the gastrointestinal tract.
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都道府県別の平均要介護期間と損失生存可能年数の地域格差と医療・福祉資源の関連について 医薬品情報に着目した地域相関研究 Reviewed
内田 博之, 中村 拓也, 金子 彩野, 大竹 一男, 内田 昌希, 小田切 陽一, 夏目 秀視, 小林 順
厚生の指標 61 ( 3 ) 15 - 24 2014.03
Language：Japanese Publisher：(一財)厚生労働統計協会
目的 平均要介護期間と年齢調整YPLL(years of potential life lost)率に着目し,各指標の都道府県別の地域格差と医療・福祉資源との関連を明らかにし,医薬品情報を含んだ関連要因の抽出を目的として地域相関研究を行った。方法 2008年の厚生労働省,総務省の各種統計資料のデータを使用し,都道府県別の平均要介護期間と年齢調整YPLL率を算出した。また,都道府県別の医療・福祉資源に関する要因のデータも得た。2つの指標と各種要因との間の相関係数を算出し,統計学的に有意な相関を示す要因を抽出した。相関マトリクスを作成し,多重共線性を配慮して候補要因を絞り,2つの指標を目的変数とした重回帰分析を行った。結果 平均要介護期間との相関が認められた要因のうち医薬品情報に関する要因として,男性では「電算処理済み処方箋1枚当たりの報酬別内訳の技術料」および「特定保険医療材料料」が抽出されたが,重回帰分析の結果からは,「糖尿病内科医師数」と「居宅介護サービスの通所介護利用者数」が関連の大きい説明変数として得られた。女性では医薬品情報に関する要因として,「電算処理済み処方箋1枚当たりの報酬別内訳の特定保険医療材料料」が抽出されたが,重回帰分析の結果からは,「リウマチ科医師数」と「居宅介護サービスの訪問介護利用者数」が関連の大きい説明変数として得られた。年齢調整YPLL率との相関が認められた要因のうち医薬品情報に関する要因として,男性では「薬剤師数」「薬局総数」「調剤の電算化率」および「後発医薬品調剤率」が抽出されたが,重回帰分析の結果からは,「後発医薬品調剤率」「特別養護老人ホームの定員」および「薬局総数」が関連の大きい説明変数として得られた。女性では医薬品情報に関する要因として,「薬局総数」「内服薬処方箋1枚当たりの薬剤料の3要素分解(1種類1日当たり薬剤料)」が抽出されたが,重回帰分析の結果からは,「呼吸器内科医師数」が説明変数として得られた。結論 相関分析の結果より,男女ともに平均要介護期間および年齢調整YPLL率に影響を与えている要因には,医薬品情報に関連した要因が説明変数の候補として抽出されたが,重回帰分析の結果より,医薬品情報と関連した要因として,男性において「後発医薬品調剤率」と「薬局総数」が年齢調整YPLL率との関連の大きい要因として把握された。(著者抄録)
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[Age, period, and birth cohort-specific effects on cervical cancer mortality rates in Japanese women and projections for mortality rates over 20-year period (2012-2031)]. Reviewed
Hiroyuki Uchida, Mizuki Kobayashi, Ami Hosobuchi, Ayano Ohta, Kazuo Ohtake, Tutomu Yamaki, Masaki Uchida, Youichi Odagiri, Hideshi Natsume, Jun Kobayashi
Nihon eiseigaku zasshi. Japanese journal of hygiene 69 ( 3 ) 215 - 24 2014
Language：Japanese Publishing type：Research paper (scientific journal)
OBJECTIVES: We aimed to determine the effects of age, period, and birth cohort on cervical cancer mortality rate trends in Japanese women, by age-period-cohort (APC) analysis. Additionally, we analyzed projected mortality rates. METHODS: We obtained data on the number of cervical cancer deaths in Japanese women from 1975-2011 from the national vital statistics and census population data. A cohort table of mortality rate data was analyzed on the basis of a Bayesian APC model. We also projected the mortality rates for the 2012-2031 period. RESULTS: The period effect was relatively limited, compared with the age and cohort effects. The age effect increased suddenly from 25-29 to 45-49 years of age and gently increased thereafter. An analysis of the cohort effect on mortality rate trends revealed a steep decreasing slope for birth cohorts born from 1908-1940 and a subsequent sudden increase after 1945. The mortality rate projections indicated increasing trends from 40 to 74 years of age until the year 2031. CONCLUSIONS: The age effect increased from 25-29 years of age. This could be attributable to the high human papilloma virus (HPV) infection risk and the low cervical cancer screening rate. The cohort effect changed from decreasing to increasing after the early 1940s. This might be attributable to the spread of cervical cancer screening and treatment before 1940 and the high HPV infection risk and reduced cervical cancer screening rate after 1945. The projected mortality rate indicated an increasing trend until the year 2031.
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Acute lethal crush-injured rats can be successfully rescued by a single injection of high-dose dexamethasone through a pathway involving PI3K-Akt-eNOS signaling. Reviewed International journal
Isamu Murata, Kazuya Ooi, Shingo Shoji, Yohei Motohashi, Miwa Kan, Kazuo Ohtake, Soichiro Kimura, Hideo Ueda, Genya Nakano, Kunihiro Sonoda, Yutaka Inoue, Hiroyuki Uchida, Ikuo Kanamoto, Yasunori Morimoto, Jun Kobayashi
The journal of trauma and acute care surgery 75 ( 2 ) 241 - 9 2013.08
Language：English Publishing type：Research paper (scientific journal)
BACKGROUND: Crush syndrome (CS) is characterized by ischemia/reperfusion-induced rhabdomyolysis and the subsequent onset of systemic inflammation. CS is associated with a high mortality, even when patients are treated with conventional therapy. We hypothesized that treatment of lethal CS rat model with dexamethasone (DEX) have therapeutic effects on the laboratory findings and clinical course and outcome. METHODS: To create a CS model, anesthetized rats were subjected to bilateral hind limb compression with rubber tourniquets for 5 hours and randomly divided into three groups as follows: saline-treated CS group, CS groups treated with low (0.1 mg/kg) and high doses (5.0 mg/kg) of DEX. Saline for the CS group or DEX for the DEX-treated CS groups was intravenously administered immediately before reperfusion. Under continuous monitoring and recording of arterial blood pressures, blood and tissue samples were collected for histologic and biochemical analysis at designated period before and after reperfusion. RESULTS: Ischemic compression of rat hind limbs reduced the nitrite content in the crushed muscle, and the subsequent reperfusion induced reactive oxygen species-mediated circulatory collapse and systemic inflammation, finally resulting in a mortality rate of 76% by 48 hours after reperfusion. A single injection of high-dose DEX immediately before reperfusion activated endothelial nitric oxide synthase (eNOS) by sequential phosphorylation through the nongenomic phosphoinositide 3-kinase (PI3K)-Akt-eNOS signaling pathway. DEX also exhibited anti-inflammatory effects by modulating proinflammatory and anti-inflammatory mediators, consequently suppressing myeloperoxidase activities and subsequent systemic inflammation, showing a complete recovery of the rats from lethal CS. CONCLUSION: These results indicate that high-dose DEX reduces systemic inflammation and contributes to the improved survival rate in a rat CS model.
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肥満を伴うインスリン抵抗性マウスに及ぼす亜硝酸塩摂取の影響に関する研究 Invited
大竹一男
日本食品化学研究振興財団研究成果報告書 ( 19 ) 2013
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デキストラン硫酸ナトリウム誘導大腸炎モデルマウスに与えるセルロース粉末の影響 Reviewed
清水 純, 紙谷 ひとみ, 大竹 一男, 内田 博之, 小林 順, 真野 博
ルミナコイド研究 16 ( 2 ) 71 - 79 2012.12
Language：Japanese Publisher：(一社)日本食物繊維学会
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Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model Reviewed International journal
Isamu Murata, Ryo Nozaki, Kazuya Ooi, Kazuo Ohtake, Soichiro Kimura, Hideo Ueda, Genya Nakano, Kunihiro Sonoda, Yutaka Inoue, Hiroyuki Uchida, Ikuo Kanamoto, Yasunori Morimoto, Jun Kobayashi
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY 72 ( 6 ) 1548 - 1554 2012.06
Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS
BACKGROUND: Nitrite is an intrinsic signaling molecule with potential therapeutic implications in mammalian ischemia/reperfusion (I/R) injury of the heart, liver, and kidney. Although limb muscle compression and subsequent reperfusion are the causative factors in developing crush syndrome (CS), there has been no report evaluating the therapeutic effects of nitrite on CS. We therefore tested whether nitrite could be a therapeutic agent for the treatment of CS.
METHODS: To create a CS model, anesthetized rats were subjected to bilateral hind limb compression with rubber tourniquets for 5 hours, followed by reperfusion for 0 hour to 6 hours while monitoring blood pressure. Saline for the CS group or sodium nitrite (NaNO2-100, 200, and 500 mu mol/kg) for the nitrite-treated CS groups was intravenously administered immediately before reperfusion. Blood and tissue samples were collected for biochemical analysis.
RESULTS: Tissue nitrite levels in injured muscles were significantly reduced in the CS group compared with the sham group during I/R injury. Nitrite administration to CS rats restored nitric oxide bioavailability by enhancing nitrite levels of the muscle, resulting in a reduction of rhabdomyolysis markers such as potassium, lactate dehydrogenase, and creatine phosphokinase. Nitrite treatment also reduced plasma levels of interleukin-6 and myeloperoxidase activities in muscle and lung tissues, finally resulting in a dose-dependent improvement of survival rate from 24% (CS group) to 36% (NaNO2-100 group) and 64% (NaNO2-200 and 500 groups).
CONCLUSION: These results indicate that nitrite reduces I/R-induced muscle damage through its cytoprotective action and contributes to improved survival rate in a rat CS model. (J Trauma Acute Care Surg. 2012;72: 1548-1554. Copyright (C) 2012 by Lippincott Williams & Wilkins). -
I 型糖尿病モデルラットにおける造影剤腎症に対する N-acetylcysteine の予防効果 Reviewed
澁谷真紀、小原由香、小島俊彦、内田昌希、大竹一男、内田博之、小林順、横田千津子、夏目秀視
Progres in Medicine. 32 119 - 125 2012.04
Language：Japanese Publishing type：Research paper (scientific journal)
Other Link： http://libir.josai.ac.jp/il/meta_pub/G0000284repository_JOS-02873648-32-659
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肥満を伴うインスリン抵抗性マウスに及ぼす亜硝酸塩摂取の影響に関する研究 Invited
大竹一男
日本食品化学研究振興財団研究成果報告書 ( 18 ) 2012
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Characterization of systemic and histologic injury after crush syndrome and intervals of reperfusion in a small animal model. Reviewed International journal
Isamu Murata, Kazuya Ooi, Hiromi Sasaki, Soichiro Kimura, Kazuo Ohtake, Hideo Ueda, Hiroyuki Uchida, Norikiyo Yasui, Yasuhiro Tsutsui, Naoya Yoshizawa, Ichiro Hirotsu, Yasunori Morimoto, Jun Kobayashi
The Journal of trauma 70 ( 6 ) 1453 - 63 2011.06
Language：English Publishing type：Research paper (scientific journal)
BACKGROUND: Prolonged compression of limb muscles and subsequent decompression are important in the development of crush syndrome (CS). We applied a simple rubber tourniquet to rat hind limbs to create a CS model. METHODS: Anesthetized rats were subjected to bilateral hind limb compression for 5 hours followed by decompression and reperfusion for 0 hour, 1 hour, 3 hours, and 24 hours under monitoring of arterial blood pressure and electrocardiography. Blood and tissue samples were collected for histology, biochemical analysis, and tissue myeloperoxidase activity assessment. RESULTS: The survival rates of the CS-model groups remained at 100% until 3 hours, however, dropped to 25% at 24 hours after reperfusion mainly because of hyperkalemia and consequent hypotension observed at 1 hour and deteriorated at 3 hours after reperfusion. Rhabdomyolysis evaluated by circulating and histologic markers of injury was found as early as 1 hour and more marked at 3 hours, resulting in impaired renal function 24 hours after reperfusion. Myeloperoxidase activities increased with incremental periods after reperfusion not only in injured limb muscles but also in kidney and lung, suggesting an abnormal interaction between the vascular endothelium and circulating leukocytes after rhabdomyolysis, possibly causing subsequent multiple organ dysfunction frequently encountered in CS. CONCLUSION: The findings from this study demonstrate the feasibility of a novel small animal model of extremity crush injury. By using this model, the impact of incremental periods of reperfusion on mortality and remote organ dysfunctions can be characterized. Future studies are necessary to better define a threshold for this injury pattern and the impact of other factors underlying this syndrome.
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[Age-, period-, and birth-cohort-specific effects on the male proportion in Japanese newborns and projections for male proportion for 20 periods (2008-2027)]. Reviewed
Hiroyuki Uchida, Mayo Watanabe, Maho Naiki, Junta Ito, Kazuo Ohtake, Youichi Odagiri, Jun Kobayashi
Nihon eiseigaku zasshi. Japanese journal of hygiene 66 ( 3 ) 582 - 8 2011.05
Language：Japanese Publishing type：Research paper (scientific journal)
OBJECTIVES: To determine the age-, period-, and cohort-specific effects on the male proportion in Japanese newborns, we performed an age-period-cohort (APC) analysis in this study. In addition, projections for the male proportion were analyzed. METHODS: We obtained data on live births of newborns for Japanese women in 1947-2007 from the National Vital Statistics. Cohort tables containing data on the male proportion were analyzed using a Bayesian APC model. Projections of the male proportion (2008-2027) were calculated. RESULTS: The age effect decreased when the mothers were 40-44 years old; however, the effect was relatively limited as compared with the period and cohort effects. The period effect increased from 1947 to 1969 and decreased thereafter. Analysis of the cohort effect on male proportion trends revealed a decreasing slope for birth cohorts born between 1905 and 1945 and a subsequent increase after 1958. The projections for male proportion indicated that the male proportion in 2027 would be similar to that in the 1970s. CONCLUSIONS: The age of the mother hardly affected the male proportion. The period effect started decreasing from the latter half of the 1960s. This may be attributable to the high economic growth since 1965 that promoted industrial development that led to environmental pollution, which in turn may have lead to the deterioration of the intrauterine environment. Cohort effects changed from 1958 and exhibited trends toward increase in male proportion; this may be due to improvements in obstetric care. Our results suggest that the male proportion in Japanese newborns will increase in the future.