Updated on 2021/12/25

写真a

 
TAKAYAMA Fusako
 
Organization
Medicine, Dentistry and Pharmaceutical Sciences Associate Professor
Position
Associate Professor
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Degree

  • Doctor of Philosophy in Pharmaceutical Sciences (Ph.D.) ( Kumamoto University )

Research Interests

  • 薬効解析

  • Biofunctional Evaluation of Medicine and Health

  • 健康機能解析

Research Areas

  • Life Science / Pharmacology

  • Life Science / Physiology

  • Life Science / Nutrition science and health science

Education

  • Kumamoto University   薬学部   薬学科

    - 1979

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    Country: Japan

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  • Kumamoto University    

    - 1979

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Research History

  • - 岡山大学医歯薬学総合研究科 准教授

    2004

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  • - Associate Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2004

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  • Research Associate,Dept. Pharmacology, Faculty of Medicine, Oita Medical University

    1991 - 2003

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  • Oita Medical University

    1991 - 2003

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Professional Memberships

Committee Memberships

  • 日本酸化ストレス学会   学術評議員  

    2011   

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    Committee type:Academic society

    日本酸化ストレス学会

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  • 日本油化学会   中国支部幹事  

    2010   

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    Committee type:Academic society

    日本油化学会

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  • 日本薬理学会   学術評議員  

    1997.1   

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  • 日本油化学会   日本油化学会第57回年会 実行委員  

    2018.9   

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    Committee type:Academic society

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  • 日本油化学会   日本油化学会関西支部幹事:地区講演会の開催  

    2012   

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    Committee type:Academic society

    日本油化学会

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  • 第43回日本薬学会・日本薬剤師会日本病院薬剤師会 中国四国支部学術大会、松江市(島根)   座長  

    2012   

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    Committee type:Academic society

    第43回日本薬学会・日本薬剤師会日本病院薬剤師会 中国四国支部学術大会、松江市(島根)

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  • 日本薬理学会   第113回日本薬理学会近畿部会 実行委員(2008)  

    2008   

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  • 第38回日本心脈管作動物質学会   事務局  

    2008   

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    Committee type:Academic society

    第38回日本心脈管作動物質学会

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  • Society for Free Radical Biology and Medicine   会員  

    2007   

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    Committee type:Academic society

    Society for Free Radical Biology and Medicine

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  • 第29回グアニジノ化合物研究会   事務局・座長  

    2007 - 2008   

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    Committee type:Academic society

    第29回グアニジノ化合物研究会

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  • 第46回日本薬学会・日本薬剤師会 日本病院薬剤師会 中国四国支部学術大会、高知市   座長  

    2007   

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    Committee type:Academic society

    第46回日本薬学会・日本薬剤師会 日本病院薬剤師会 中国四国支部学術大会、高知市

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  • 第80回日本薬理学会年会、名古屋市   座長  

    2006   

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    第80回日本薬理学会年会、名古屋市

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  • 日本医療薬学会   会員  

    2004 - 2012   

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    Committee type:Academic society

    日本医療薬学会

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  • 第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会、松江市   座長  

    2004   

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    第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会、松江市

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Papers

  • Regulatory effects of nicotine on neurite outgrowth in rat superior cervical ganglia cells.

    Hiromu Kawasaki, Hayato Hino, Fusako Takayama, Yoshihisa Kitamura, Toshiaki Sendou, Shingo Takatori

    Journal of pharmacological sciences   148 ( 1 )   103 - 107   2022.1

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    We have reported that nicotine has a neurotrophic action on peripheral adrenergic nerves in vivo, which is mediated by α7 nicotinic acetylcholine receptors (nAChRs). To clarify the possible mechanisms, the present study further investigated the effect of nicotine on neurite outgrowth in tyrosine hydroxylase (TH)-positive superior cervical ganglia (SCG) cells isolated from neonatal rats in vitro. Nicotine at low concentrations (0.01-0.3 mM) increased the number of neurite outgrowths in TH-immunopositive SCG cells, while high concentrations of nicotine (1-10 mM) gradually reduced it, and only 10 mM nicotine was markedly inhibited compared to the control. A 100 μM of nicotine-induced increase in neurite numbers depended on the exposure time and was inhibited by treatment with the nAChR antagonist hexamethonium (Hex) and α7 nAChR antagonist α-bungarotoxin (α-Bgtx). The nicotine (10 mM)-induced a significant decrease in neurite outgrowth in SCG, which was perfectly canceled by Hex to the control level but not by α-Bgtx. These results suggest that nicotine has a regulatory neurotrophic action mediated by both α7 nAChR and other subtypes in TH-positive SCG cells of rats.

    DOI: 10.1016/j.jphs.2021.10.012

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  • Spirulina platensis and its ingredient biopterin glucoside improved insulin sensitivity in non-alcoholic steatohepatitis model.

    Yuri Fujihara, Yasumasa Kodo, Shin-Ichi Miyoshi, Ritsuko Watanabe, Hiroshi Toyoda, Mitsumasa Mankura, Hideaki Kabuto, Fusako Takayama

    Journal of clinical biochemistry and nutrition   69 ( 2 )   151 - 157   2021.9

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    Non-alcoholic steatohepatitis is the chronic liver disease leading to cirrhosis and cancer and its prevalence is increasing. Some agents are under clinical trials for non-alcoholic steatohepatitis treatment. We previously reported Spirulina (Arthrospira) platensis effectively prevented non-alcoholic steatohepatitis progression in our model rats. The contribution of phycocyanin, an ingredient of Spirulina (Arthrospira) platensis, was limited. We, therefore, have looked for more active components of Spirulina (Arthrospira) platensis. In this study, we pursued the effect of biopterin glucoside, another bioactive ingredient of Spirulina (Arthrospira) platensis. We found Spirulina (Arthrospira) platensis and biopterin glucoside oral administrations effectively alleviated oxidative stress, inflammation and insulin signal failure, and prevented fibroblast growth factor 21 gene overexpression in non-alcoholic steatohepatitis rat livers. We concluded biopterin glucoside is a major component of Spirulina (Arthrospira) platensis action.

    DOI: 10.3164/jcbn.20-201

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  • Opposite Effects of Metformin against Non-Alcoholic Fatty Liver Disease, Depend on Steatosis Grade

    Fusako Takayama, Yuri Fujihara, Tsuno Wataru, Kamatani Haruka, Kabuto Hideaki, Mankura Mitsumasa

    Advances in Clinical Toxicology   4 ( 2 )   2019.5

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Medwin Publishers  

    DOI: 10.23880/act-16000157

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  • How does Eucommia leaf extract prevent smooth muscle cell proliferation induced by high-fat diets at the aortic tunica media? International journal

    Fusako Takayama, Yuri Fujihara

    Hypertension research : official journal of the Japanese Society of Hypertension   40 ( 6 )   541 - 543   2017.6

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    DOI: 10.1038/hr.2017.22

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  • Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries.

    Panot Tangsucharit, Shingo Takatori, Yoshito Zamami, Mitsuhiro Goda, Poungrat Pakdeechote, Hiromu Kawasaki, Fusako Takayama

    Journal of pharmacological sciences   130 ( 1 )   24 - 32   2016.1

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    The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR) subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol) produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol) disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist) or 4-DAMP (M1 and M3 antagonist) plus hexamethonium (nicotinic AChR antagonist), but not methoctramine (M2 and M4 antagonist). These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation.

    DOI: 10.1016/j.jphs.2015.12.005

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  • Nicotine facilitates reinnervation of phenol-injured perivascular adrenergic nerves in the rat mesenteric resistance artery. International journal

    Shingo Takatori, Hidetoshi Fujiwara, Kenta Hagimori, Narumi Hashikawa-Hobara, Ayako Yokomizo, Fusako Takayama, Panot Tangsucharit, Nobufumi Ono, Hiromu Kawasaki

    European journal of pharmacology   748   1 - 9   2015.2

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    Nicotine has been shown to have neuroprotective and neurotrophic actions in the central nervous system. To elucidate the peripheral neurotrophic effects of nicotine, we determined whether nicotine affected the reinnervation of mesenteric perivascular nerves following a topical phenol treatment. A topical phenol treatment was applied to the superior mesenteric artery proximal to the abdominal aorta in Wistar rats. We examined the immunohistochemistry of the distal small arteries 7 days after the treatment. The topical phenol treatment markedly reduced the density of tyrosine hydroxylase (TH)-LI and calcitonin gene-related peptide (CGRP)-LI fibers in these arteries. The administration of nicotine at a dose of 3 mg/kg/day (1.5 mg/kg/injection, twice a day), but not once a day or its continuous infusion using a mini-pump significantly increased the density of TH-LI nerves without affecting CGRP-LI nerves. A pretreatment with nicotinic acetylcholine receptor antagonists hexamethonium, mecamylamine, and methyllycaconitine, but not dextrometorphan, canceled the TH-LI nerve reinnervation induced by nicotine. Nicotine significantly increased NGF levels in the superior cervical ganglia (SCG) and mesenteric arteries, but not in the dorsal root ganglia, and also up-regulated the expression of NGF receptors (TrkA) in the SCG, which were canceled by hexamethonium. These results suggested that nicotine exhibited neurotrophic effects that facilitated the reinnervation of adrenergic TH-LI nerves by activating α7 nicotinic acetylcholine receptor and NGF in the SCG.

    DOI: 10.1016/j.ejphar.2014.12.005

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  • Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats. International journal

    Tomoko T Yamanushi, Hideaki Kabuto, Eiichiro Hirakawa, Najma Janjua, Fusako Takayama, Mitsumasa Mankura

    The Journal of nutrition   144 ( 4 )   467 - 74   2014.4

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    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

    DOI: 10.3945/jn.113.175125

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  • Oral Administration of Eicosapentaenoic Acid or Docosahexaenoic Acid Modifies Cardiac Function and Ameliorates Congestive Heart Failure in Male Rats Reviewed

    Tomoko T. Yamanushi, Hideaki Kabuto, Eiichiro Hirakawa, Najma Janjua, Fusako Takayama, Mitsumasa Mankura

    JOURNAL OF NUTRITION   144 ( 4 )   467 - 474   2014.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC NUTRITION-ASN  

    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA ethyl ester (EPA-Et; E group), or DHA ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P <= 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P <= 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P <= 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P <= 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P <= 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

    DOI: 10.3945/jn.133.175125

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  • Oral Administration of Eicosapentaenoic Acid or Docosahexaenoic Acid Modifies Cardiac Function and Ameliorates Congestive Heart Failure in Male Rats. Reviewed International journal

    Tomoko T Yamanushi, Hideaki Kabuto, Eiichiro Hirakawa, Najima Janjua, Fusako Takayama, Mitsumasa Mankura

    J. Nutrition,   12 ( 4 )   1 - 8   2014

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    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

    DOI: 10.3945/jn.113.175125

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  • Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson’s disease model mouse. Reviewed

    Hideaki Kabuto, Tomoko T Yamanushi, Najma Janjua, Fusako Takayama, Mitsumasa Mankura

    Journal of Oleo Science.   62 ( 1 )   21 - 28   2013

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    Active oxygen has been implicated in the pathogenesis of Parkinson's disease (PD); therefore, antioxidants have attracted attention as a potential way to prevent this disease. Squalene, a natural triterpene and an intermediate in the biosynthesis of cholesterol, is known to have active oxygen scavenging activities. Squalane, synthesized by complete hydrogenation of squalene, does not have active oxygen scavenging activities. We examined the effects of oral administration of squalene or squalane on a PD mouse model, which was developed by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA). Squalene administration 7 days before and 7 days after one 6-OHDA injection prevented a reduction in striatal dopamine (DA) levels, while the same administration of squalane enhanced the levels. Neither squalene nor squalane administration for 7 days changed the levels of catalase, glutathione peroxidase, or superoxide dismutase activities in the striatum. Squalane increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, in the striatum. Both squalane and squalene increased the ratio of linoleic acid/linolenic acid in the striatum. These results suggest that the administration of squalene or squalane induces similar changes in the composition of fatty acids and has no effect on the activities of active oxygen scavenging enzymes in the striatum. However, squalane increases oxidative damage in the striatum and exacerbates the toxicity of 6-OHDA, while squalene prevents it. The effects of squalene or squalane treatment in this model suggest their possible uses and risks in the treatment of PD.

    DOI: 10.5650/jos.62.21

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  • Do cholinergic nerves innervating rat mesenteric arteries regulate vascular tone? International journal

    Panot Tangsucharit, Shingo Takatori, Pengyuan Sun, Yoshito Zamami, Mitsuhiro Goda, Poungrat Pakdeechote, Fusako Takayama, Hiromu Kawasaki

    American journal of physiology. Regulatory, integrative and comparative physiology   303 ( 11 )   R1147-56   2012.12

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    Vascular blood vessels have various types of cholinergic acetylcholine receptors (AChR), but the source of ACh has not been confirmed. Perivascular adrenergic nerves and nonadrenergic calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerves innervate rat mesenteric arteries and regulate vascular tone. However, function of cholinergic innervation remains unknown. The present study investigated cholinergic innervation by examining effects of cholinesterase inhibitor (neostigmine), a muscarinic AChR antagonist (atropine), and a nicotinic AChR antagonist (hexamethonium) on adrenergic nerve-mediated vasoconstriction and CGRPergic nerve-mediated vasodilation in rat mesenteric vascular beds without endothelium. In preparations treated with capsaicin (CGRP depletor) or in the presence of N(ω)-nitro-l-arginine methyl ester (nonselective nitric oxide synthase inhibitor), perivascular nerve stimulation (PNS; 2-12 Hz) evoked a frequency-dependent vasoconstriction. In the same preparations, exogenous norepinephrine induced a concentration-dependent vasoconstriction. Atropine, hexamethonium, and neostigmine had no effect on vasoconstrictor responses to PNS and norepinephrine injections. In denuded preparations, these cholinergic agents did not affect the PNS (12 Hz)-evoked release of norepinephrine in perfusate. In preconstricted preparations without endothelium in the presence of guanethidine (adrenergic neuron blocker), PNS (1-4 Hz) induced a frequency-dependent vasodilation, which was not affected by atropine, hexamethonium, and neostigmine. In denuded preparations treated with capsaicin and guanethidine, PNS did not induce vascular responses, and atropine, neostigmine, and physostigmine had no effect on PNS. Immunohistochemistry study showed choline acetyltransferase-immunopositive fibers, which were resistant to capsaicin and 6-hydroxydopamine (adrenergic toxin). These results suggest that rat mesenteric arteries have cholinergic innervation, which is different from adrenergic and capsaicin-sensitive nerves and not associated with vascular tone regulation.

    DOI: 10.1152/ajpregu.00317.2012

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  • Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis.

    Wing Pak, Fusako Takayama, Manaka Mine, Kazuo Nakamoto, Yasumasa Kodo, Mitsumasa Mankura, Toru Egashira, Hiromu Kawasaki, Akitane Mori

    Journal of clinical biochemistry and nutrition   51 ( 3 )   227 - 34   2012.11

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    The pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, but accumulating data suggest oxidative stress and the relationship between inflammation and immunity plays a crucial role. The aim of this study is to investigate the spirulina, which is a blue-green algae rich in proteins and other nutritional elements, and its component-phycocyanin effect on a rat model of NASH. NASH model rats were established by feeding male Wistar rats with choline-deficient high-fat diet (CDHF) and intermittent hypoxemia by sodium nitrite challenge after 5 weeks of CDHF. After experimental period of 10 weeks, blood and liver were collected to determine oxidative stress injuries and efficacies of spirulina or phycocyanin on NASH model rats. In the NASH model rats, increase in plasma liver enzymes and liver fibrosis, increases in productions of reactive oxygen species from liver mitochondria and from leukocytes, the activation of nuclear factor-kappa B, and the change in the lymphocyte surface antigen ratio (CD4(+)/CD8(+)) were observed. The spirulina and phycocyanin administration significantly abated these changes. The spirulina or phycocyanin administration to model rats of NASH might lessen the inflammatory response through anti-oxidative and anti-inflammatory mechanisms, breaking the crosstalk between oxidative stress and inflammation, and effectively inhibit NASH progression.

    DOI: 10.3164/jcbn.12-18

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  • Water Extract of Vitis coignetiae Pulliat Leaves Attenuates Oxidative Stress and Inflammation in Progressive NASH Rats Reviewed

    Wing Pak, Fusako Takayama, Azusa Hasegawa, Mitsumasa Mankura, Toru Egashira, Keiji Ueki, Kazuo Nakamoto, Hiromu Kawasaki, Akitane Mori

    ACTA MEDICA OKAYAMA   66 ( 4 )   317 - 327   2012.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OKAYAMA UNIV MED SCHOOL  

    This study aimed to investigate the therapeutic effects of the water extract of leaves of Vitis coignetiae Pulliat (VCPL) on nonalcoholic steatohepatitis (NASH) with advanced fibrosis, as our previous study exhibited its preventive effect on NASH. The NASH animal model [PCT/JP2007/52477] was prepared by loading recurrent and intermittent hypoxemia stress to a rat with fatty liver, which resembled the condition occurring in patients with obstructive sleep apnea (OSA) and fatty liver, who have a high incidence of NASH. Intermittent hypoxemia stress is regarded as a condition similar to warm ischemia followed by re-oxygenation, which induces oxidative stress (OS). The daily 100 or 300 mg/kg VCPL administrations were performed for 3 weeks perorally beginning at the time of detection of advanced liver fibrosis. The therapeutic efficacy of VCPL on NASH was demonstrated by the reduction of the leakage of hepato-biliary enzymes and the amelioration of liver fibrosis. The OS elevation in NASH rats was measured based on the derivation of reactive oxygen species from liver mitochondrial energy metabolism and on the decrease in plasma SOD-like activity. The aggravation of inflammatory responses was demonstrated by the neutrophil infiltration (elevated myeloperoxidase activity) and the progression of fibrosis in the livers of NASH rats. In addition, the NASH rats without VCPL treatment also exhibited activation of nuclear factor-kappa B, a key factor in the link between oxidative stress and inflammation. All of these changes were reduced dose-dependently by the VCPL administration. These findings indicate that VCPL may improve hepatic fibrosis or at least suppress the progression of NASH, by breaking the crosstalk between OS and inflammation.

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  • Water extract of Vitis coignetiae Pulliat leaves attenuates oxidative stress and inflammation in progressive NASH rats.

    Wing Pak, Fusako Takayama, Azusa Hasegawa, Mitsumasa Mankura, Toru Egashira, Keiji Ueki, Kazuo Nakamoto, Hiromu Kawasaki, Akitane Mori

    Acta medica Okayama   66 ( 4 )   317 - 27   2012

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    This study aimed to investigate the therapeutic effects of the water extract of leaves of Vitis coignetiae Pulliat (VCPL) on nonalcoholic steatohepatitis (NASH) with advanced fibrosis, as our previous study exhibited its preventive effect on NASH. The NASH animal model [PCT/JP2007/52477] was prepared by loading recurrent and intermittent hypoxemia stress to a rat with fatty liver, which resembled the condition occurring in patients with obstructive sleep apnea (OSA) and fatty liver, who have a high incidence of NASH. Intermittent hypoxemia stress is regarded as a condition similar to warm ischemia followed by re-oxygenation, which induces oxidative stress (OS). The daily 100 or 300 mg/kg VCPL administrations were performed for 3 weeks perorally beginning at the time of detection of advanced liver fibrosis. The therapeutic efficacy of VCPL on NASH was demonstrated by the reduction of the leakage of hepato-biliary enzymes and the amelioration of liver fibrosis. The OS elevation in NASH rats was measured based on the derivation of reactive oxygen species from liver mitochondrial energy metabolism and on the decrease in plasma SOD-like activity. The aggravation of inflammatory responses was demonstrated by the neutrophil infiltration (elevated myeloperoxidase activity) and the progression of fibrosis in the livers of NASH rats. In addition, the NASH rats without VCPL treatment also exhibited activation of nuclear factor-κB, a key factor in the link between oxidative stress and inflammation. All of these changes were reduced dose-dependently by the VCPL administration. These findings indicate that VCPL may improve hepatic fibrosis or at least suppress the progression of NASH, by breaking the crosstalk between OS and inflammation.

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  • Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator-activated receptor (PPAR) α-selective agonists. International journal

    Shintaro Ban, Jun-ichi Kasuga, Izumi Nakagome, Hiromi Nobusada, Fusako Takayama, Shuichi Hirono, Hiromu Kawasaki, Yuichi Hashimoto, Hiroyuki Miyachi

    Bioorganic & medicinal chemistry   19 ( 10 )   3183 - 91   2011.5

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    A series of α-ethylphenylpropanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) α-selective agonists, based on our PPARα/δ dual agonist 3 as a lead compound. Structure-activity relationship studies clearly indicated that the steric bulkiness and position of the distal hydrophobic tail part are critical for PPARα agonistic activity and PPARα selectivity, as had been predicted from a molecular-modeling study. A representative compound blocked the progression of nonalcoholic steatohepatitis (NASH) in an animal model.

    DOI: 10.1016/j.bmc.2011.03.064

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  • Effects of docosahexaenoic acid in an experimental rat model of nonalcoholic steatohepatitis.

    Fusako Takayama, Kazuo Nakamoto, Nagao Totani, Tomoko Yamanushi, Hideaki Kabuto, Takao Kaneyuki, Mitsumasa Mankura

    Journal of oleo science   59 ( 8 )   407 - 14   2010

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    Docosahexaenoic acid (DHA) regulates the lipid metabolism and inflammation that is closely associated with oxidative stress. The present study investigated the effects of DHA on the development of nonalcoholic steatohepatitis (NASH). To induce fatty liver, rats were fed choline-deficient high-fat diets (CDHF). The rats were then divided into 4 groups treated over the subsequent 6 weeks as follows: control, CDHF, CDHF+oxidative stress (NASH), and NASH+DHA (1.0 g/kg, p.o.). Rats of the control group were fed MF chow diet only. NASH rats showed severe steatohepatitis and liver fibrosis. Treatment with DHA significantly decreased the n-6/n-3 ratio in the livers and increased plasma SOD like activity compared with NASH rats. In addition, DHA attenuated the liver fibrosis during NASH development. Therefore, a higher DHA ratio in the liver of NASH rats might regulate the inflammatory response through a low n-6 ratio and diminished oxidative stress, effectively inhibiting liver fibrosis during NASH progression. These results suggested that DHA is a novel functional food for the prevention of NASH.

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  • A Novel Animal Model of Nonalcoholic Steatohepatitis (NASH): Hypoxemia Enhances the Development of NASH.

    Fusako Takayama, Toru Egashira, Hiromu Kawasaki, Mitsumasa Mankura, Kazuo Nakamoto, Shigeru Okada, Akitane Mori

    Journal of clinical biochemistry and nutrition   45 ( 3 )   335 - 40   2009.11

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    Recent reports described a high incidence of nonalcoholic steatohepatitis (NASH) in patients with obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans. Chemical hypoxemia through methemoglobinemia was induced by daily intraperitoneal injection of sodium nitrite (40 mg/kg) for 4 weeks in rats with fatty liver. The later was induced by 4-week feeding a choline-deficient high-fat diet (CDHF). Besides, the normal chow diets feeding groups were prepared with in the same manner except for CDHF feeding. The animal experiment was performed in four groups; Normal control, Hypoxemia, CDHF, and CDHF + hypoxemia. Nitrite was given for the later 4 weeks to each rat of Hypoxemia and CDHF + hypoxemia. CDHF + hypoxemia rats were confirmed to develop histological changes that resemble those of patients with NASH, together with biochemical liver dysfunction, while CDHF group was limited in mild steatosis, and Hypoxemia group liver was normal. Present study established a reproducible and useful NASH model resembling the main features of NASH in humans, and showed first that recurrent and intermittent hypoxemia aggravate fatty liver to steatohepatitis and liver fibrosis.

    DOI: 10.3164/jcbn.09-29

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  • A Novel Animal Model of Nonalcoholic Steatohepatitis (NASH): Hypoxemia Enhances the Development of NASH Reviewed

    Fusako Takayama, Toru Egashira, Hiromu Kawasaki, Mitsumasa Mankura, Kazuo Nakamoto, Shigeru Okada, Akitane Mori

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   45 ( 3 )   335 - 340   2009.11

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    Recent reports described a high incidence of nonalcoholic steatohepatitis (NASH) in patients with obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans. Chemical hypoxemia through methemoglobinemia was induced by daily intraperitoneal injection of sodium nitrite (40 mg/kg) for 4 weeks in rats with fatty liver. The later was induced by 4-week feeding a choline-deficient high-fat diet (CDHF). Besides, the normal chow diets feeding groups were prepared with in the same manner except for CDHF feeding. The animal experiment was performed in four groups; Normal control, Hypoxemia, CDHF, and CDHF + hypoxemia. Nitrite was given for the later 4 weeks to each rat of Hypoxemia and CDHF + hypoxemia. CDHF + hypoxemia rats were confirmed to develop histological changes that resemble those of patients with NASH, together with biochemical liver dysfunction, while CDHF group was limited in mild steatosis, and Hypoxemia group liver was normal. Present study established a reproducible and useful NASH model resembling the main features of NASH in humans, and showed first that recurrent and intermittent hypoxemia aggravate fatty liver to steatohepatitis and liver fibrosis.

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  • Beneficial effects of Vitis coignetiae Pulliat leaves on nonalcoholic steatohepatitis in a rat model.

    Fusako Takayama, Kazuo Nakamoto, Hiromu Kawasaki, Mitsumasa Mankura, Toru Egashira, Keiji Ueki, Azusa Hasegawa, Shigeru Okada, Akitane Mori

    Acta medica Okayama   63 ( 2 )   105 - 11   2009.4

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    Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on the abundant polyphenols and anthocyanins in its fruit. However, it is not known whether the leaves of this plant confer similar benefits. This study investigated the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH). Rats were fed a choline-deficient high-fat diet for four weeks to generate fatty livers. NASH was induced by oxidative stress loading. Ten weeks later, blood and liver samples were collected from anesthetized animals and assessed biochemically, histologically, and histochemically to determine the extent of oxidative stress injury and the overall effects of VCPL. Six-week VCPL extract supplementation reduced serum levels of liver enzymes, decreased CYP2E1 induction, increased plasma antioxidant activities and delayed the progression of liver fibrosis. The findings suggested that VCPL has strong radical-scavenging activity and may be beneficial in preventing NASH progression.

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  • [Effect of postprandial hyperglycemia and hyperinsulinemia on vascular responsiveness].

    Yoshito Zamami, Shingo Takatori, Yukiko Iwatani, Kousuke Yamawaki, Satoko Miyashita, Nana Yabumae, Fusako Takayama, Mitsunobu Mio, Hiromu Kawasaki

    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan   128 ( 3 )   419 - 24   2008.3

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    Recent clinical studies demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II, calcitonin gene-related peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentration of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting injection of pressor responses to noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nerve-mediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemic, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increases adrenergic nerve-mediated vasoconstriction, which is partly associated with the blunted CGRPergic nerve function, and that plasma insulin concentration associated with hyperglycemia may be responsible for alteration of neuronal vascular regulation.

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  • Involvement of angiotensin type 1 receptors in altered neuronal vascular regulation in acute hyperinsulinemia Reviewed

    Yoshito Zamami, Shingo Takatori, Kousuke Yamawaki, Satoko Miyashita, Nana Yabumae, Fusako Takayama, Yoshihisa Kitamura, Mitsunobu Mio, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   56P - 56P   2008

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  • [Mechanisms underlying enhanced vasodilator responses to various vasodilator agents following endothelium removal in rat mesenteric resistance arteries].

    Yukiko Iwatani, Hiromi Numa, Saori Atagi, Fusako Takayama, Mitsunobu Mio, Hiromu Kawasaki

    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan   127 ( 4 )   729 - 33   2007.4

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    We reported that vasodilator responses to various vasodilator agents were augmented by endothelium removal. To explain this mechanism, we hypothesized that endothelium removal eliminates the release of endothelium-derived contracting factor EDCF, which counteracts the vasodilation. However, the underlying mechanism is unknown. Therefore the present study investigated the second messenger system further to investigate the mechanisms underlying enhanced vasodilator response after endothelium removal in rat mesenteric resistance arteries. Mesenteric vascular beds isolated from Wistar rats were perfused and perfusion pressure was measured. The vascular endothelium was removed by 30-s perfusion of sodium deoxycholate. Vasodilator responses to sodium nitroprusside (SNP) perfusion were markedly augmented and prolonged by endothelium removal. In preparations with intact endothelium and active tone, 5-min perfusion of sodium azide (non-specific guanylate cyclase (GC) activator), ANP (membrane-linked GC activator), and 8-Br-cGMP (cGMP analogue) caused a concentration-dependent vasodilation that was markedly augmented by endothelium removal. However, vasodilation induced by YC-1 and BAY41-2272 (selective soluble GC activator) was not augmented by endothelium removal. When methylene blue (soluble GC inhibitor) was present in the medium, SNP caused a concentration-dependent vasodilation in the preparation with intact endothelium, which was less augmented by endothelium removal compared with control (preparation without methylene blue). These findings suggest that endothelium removal affects intracellular cGMP-mediated signal transduction system in vascular smooth muscle cells.

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  • Distribution of perivascular nerves in neovasculatures in mice. Reviewed

    Mitsuhiro Goda, Saori Atagi, Keisuke Amitani, Yoshihisa Kitamura, Fusako Takayama, Hiromu Kawasaki

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN   127   148 - 149   2007

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    Angiogenesis is critical for the growth and spread of tumors. Since perivascular nerves maintain vascular tone and regulate organ and tissue blood flow, it is hypothesized that the neuronal regulation of blood flow toward tumors by perivascular nerves may lead to suppress the tumor growth. However, it. is not known whether neovessels resulted from angiogenesis have innervation of perivascular nerves. Therefore, the present study was designed to investigate the distribution of perivascular nerves in neovasculatures and effect of nerve growth factor (NGF) on perivascular innervation in mice. A Matrigel was subcutaneously implanted in the mouse. The presence of perivascular nerves in Matrigel on Day 3 to 21 after the implantation was immunohistochemically studied by immunostaining using PGP9.5 antibody. NGF or saline was subcutaneously administered by an osmotic mini-pump. Immunostaining of neovasculatures in Matrigel showed the presence of perivascular nerves on Day 21 after Matrigel injection. Perivascular innervation of neovessels within Marigel implanted in NGF-treated mice was observed in Day 17 after Matrigel implantation. However, NGF treatment did not increase numbers of neovessels in Matrigel. These results suggest that perivascular nerves innervate neovessels as neovasculatures mature and that NGF accelerates innervation of perivascular nerves in neovessels.

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  • Neuronal nitric-oxide synthase inhibition facilitates adrenergic neurotransmission in rat mesenteric resistance arteries. International journal

    Yukako Hatanaka, Narumi Hobara, Jin Honghua, Shinji Akiyama, Hideki Nawa, Yuta Kobayashi, Fusako Takayama, Yutaka Gomita, Hiromu Kawasaki

    The Journal of pharmacology and experimental therapeutics   316 ( 2 )   490 - 7   2006.2

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    The effects of nonselective nitric-oxide synthase (NOS) inhibitors [N-omega-nitro-L-arginine methyl ester (L-NAME) and N-omega-nitro-L-arginine (L-NNA)] and specific neuronal NOS (nNOS) inhibitor [vinyl-L-N-5-(1-imino-3-butenyl)-L-ornithine (L-VNIO)] on adrenergic nerve-mediated vasoconstriction were studied in rat perfused mesenteric vascular beds without endothelium. Perfusion of L-NAME, L-NNA, or l-VNIO markedly augmented vasoconstrictor responses to periarterial nerve stimulation (PNS; 2-8 Hz) without affecting vasoconstriction induced by exogenously injected norepinephrine (NE). Addition of L-arginine, a precursor for the synthesis of nitric oxide (NO), reversed the augmentation of the PNS response by l-NAME. The PNS (8 Hz)-evoked NE release in the perfusate was increased by L-NAME perfusion. In preparations treated with capsaicin [a depleter of calcitonin gene-related peptide (CGRP)-containing nerves], L-NAME did not augment vasoconstrictor responses to PNS or NE injection. Combined perfusion of CGRP(8-37) (a CGRP receptor antagonist) and L-NAME induced additive augmentation of the vasoconstrictor response to PNS but did not affect the response to NE injection. In preparations with active tone produced by methoxamine and in the presence of guanethidine, L-NAME perfusion did not affect the vasodilator response induced by PNS. Immunostaining of the mesenteric artery showed the presence of nNOS-like immunopositive nerve fibers, which were absent in arteries pretreated with capsaicin. These findings suggest that NO, which is released from perivascular capsaicin-sensitive nerves, presynaptically inhibits neurogenic NE release to modulate adrenergic neurotransmission.

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  • Histamine-induced vasodilation and vasoconstriction in the mesenteric resistance artery of the rat. International journal

    Honghua Jin, Toshihiro Koyama, Yukako Hatanaka, Shinji Akiyama, Fusako Takayama, Hiromu Kawasaki

    European journal of pharmacology   529 ( 1-3 )   136 - 44   2006.1

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    The present study was designed to examine the vascular response to histamine in rat perfused mesenteric vascular beds with active tone. In preparations with intact endothelium, perfusion of histamine (1 nM-100 microM) produced a concentration-dependent vasodilation. Histamine-induced vasodilation was attenuated by L-NAME (nitric oxide (NO) synthase inhibitor, 100 microM) and olopatadine (histamine H(1) receptor antagonist, 1 microM) but not by lafutidine (histamine H(2) receptor antagonist, 1 microM). Cold-storage denervation (4 degrees C for 72 h) of the preparation with intact endothelium attenuated the histamine-induced vasodilation. In preparations without endothelium, histamine at low concentrations (1-100 nM) produced only a small and rapid vasodilation, whereas histamine at concentrations higher than 1 muM produced triphasic vascular responses: initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. Lafutidine abolished only the histamine-induced initial vasodilation. Olopatadine abolished the histamine-induced second vasoconstriction and third vasodilation. Cold-storage denervation of the denuded preparation abolished the histamine-induced second vasoconstriction and third vasodilation. These findings suggest that histamine induced endothelium-dependent vasodilation via endothelium histamine H(1) receptors and endothelium-independent vasodilation via smooth muscle histamine H(2) receptors. It is also suggested that the histamine-induced endothelium-independent vasoconstriction and vasodilation are mediated by histamine H(1) receptors and perivascular nerves.

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  • Effect of adrenomedullin on adrenergic vasoconstriction in mesenteric resistance arteries of the rat.

    Shinji Akiyama, Yukako Hatanaka, Narumi Hobara, Jin Honghua, Keiji Kosugi, Fusako Takayama, Hiromu Kawasaki

    Journal of pharmacological sciences   99 ( 3 )   264 - 71   2005.11

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    Adrenomedullin (AM) is a hypotensive peptide that belongs to a family of peptides structurally related to calcitonin gene-related peptide (CGRP). The present study examined the effect of AM on adrenergic nerve-mediated vasoconstriction in rat perfused mesenteric vascular beds without endothelium. Perfusion of AM at 0.1 nM but not 10 nM increased vasoconstrictor responses to periarterial nerve stimulation (PNS) (1-4 Hz), while AM at 10 nM significantly attenuated vasoconstriction induced by bolus injection of norepinephrine (NE). In preparations treated with capsaicin (a CGRP depletor), pressor responses to both PNS and NE injection were markedly attenuated by AM. Perfusion of CGRP(8-37) (a CGRP-receptor antagonist) significantly potentiated the PNS- but not the NE-induced vasoconstriction. Combined perfusion of CGRP(8-37) and AM had no effect on the PNS-induced response and antagonized the inhibitory effect of AM on the NE-induced response. AM(2-52) (an AM-receptor antagonist) did not influence the effect of AM. These findings suggest that AM facilitates adrenergic vasoconstriction by inhibiting neurotransmission of CGRP-containing nerves, which counteract adrenergic nerve-mediated vasoconstriction.

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  • Long-term inhibition of angiotensin prevents reduction of periarterial innervation of calcitonin gene-related peptide (CGRP)-containing nerves in spontaneously hypertensive rats. International journal

    Narumi Hobara, Noriko Gessei-Tsutsumi, Mitsuhiro Goda, Fusako Takayama, Shinji Akiyama, Yuji Kurosaki, Hiromu Kawasaki

    Hypertension research : official journal of the Japanese Society of Hypertension   28 ( 5 )   465 - 74   2005.5

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    The aim of this study was to investigate age-related changes in the density of calcitonin gene-related peptide (CGRP)-containing nerve fibers in spontaneously hypertensive rats (SHR) and the effects of long-term inhibition of the renin-angiotensin system on these changes. The density of immunocytochemically stained nerve fibers in the mesenteric artery was quantified by computer-assisted image processing. An age-related decrease in the density of CGRP-like immunoreactive (LI)-containing nerve fivers but not neuropeptide Y (NPY)-LI-containing sympathetic nerve fibers was found in the mesenteric artery of SHR but not Wistar Kyoto rats (WKY). The density of NPY-LI-containing sympathetic nerve fibers was significantly greater in SHR than in WKY. SHR were treated for 7 weeks with angiotensin converting enzyme inhibitor (0.005% temocapril), angiotensin II type-1 (AT1) receptor antagonist (0.025% losartan) or vasodilator (0.01% hydralazine) in their drinking water. Each drug treatment significantly lowered the systolic blood pressure measured by tail-cuff method. Long-term treatment of SHR with temocapril and losartan significantly increased the density of CGRP-LI-containing nerve fibers in mesenteric arteries. However, the density after hydralazine treatment was similar to the level in non-treated SHR. The density of NPY-LI-containing nerve fibers was not increased by any of the drug treatments. These results suggest that long-term inhibition of the renin-angiotensin system in SHR prevents remodeling of CGRPergic nerve fibers and prevents the reduction of CGRPergic nerve function.

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  • Zinc benzoate, a contaminating environmental compound derived from polystyrene resin inhibits A-type monoamine oxidase. International journal

    Toru Egashira, Kumiko Sakai, Fusako Takayama, Mami Sakurai, Satoshi Yoshida

    Toxicology letters   145 ( 2 )   161 - 5   2003.11

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    The contaminants in deionized and distilled water (DDI water) boiled with polystyrene resin inhibited A-type monoamine oxidase (MAO, MAO-A preferentially deaminates serotonin and norepinephrine and regulates these amines concentration) activity in monkey brain mitochondria. To identify these contaminants, we attempted measurements by HPLC, FT-IR and NMR. The compound inhibiting MAO-A activity was zinc benzoate. Although it potently inhibited MAO-A activity, zinc benzoate did not effect MAO-B in monkey brain mitochondria. It also reversibly and competitively inhibited MAO-A activity in a dose-dependent manner. Zinc benzoate, however, did not inhibit either MAO-A or -B activities in rat brain mitochondria. These results indicate that zinc benzoate, which inhibits MAO-A activity, is easily incorporated in DDI water by boiling polystyrene and also may be a contaminating environmental chemical compound that alters the levels of serotonin and norepinephrine in the central nervous system.

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  • Calcium disodium edetate enhances type A monoamine oxidase activity in monkey brain. International journal

    Toru Egashira, Kumiko Sakai, Mami Sakurai, Fusako Takayama

    Biological trace element research   94 ( 3 )   203 - 11   2003.9

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    The effects of metal chelators on monoamine oxidase (MAO) isozymes, MAO-A and MAO-B, in monkey brain mitochondria were investigated in vitro. MAO-A activity increased to about 40% with 0.1 microM calcium disodium edetate (CaNa2EDTA) using serotonin as a substrate, and this activation was proportional to the concentration of CaNa2EDTA. On the other hand, MAO-A activities were decreased gradually with an increasing concentration of o-phenanthroline and diethyldithiocarbamic acid, but these metal chelators had no effect on MAO-B activity in monkey brain. The activation of MAO-A activity by CaNa2EDTA was reversible. CaNa2EDTA did not activate both MAO-A and MAO-B activities in rat brain mitochondria. Zn and Fe ions were found in the mitochondria of monkey brain. Zn ions potently inhibited MAO-A activity, but Fe ions did not inhibit either MAO-A or MAO-B activity in monkey brain mitochondria. These results indicate that the activating action of CaNa2EDTA on MAO-A was the result of the chelating of Zn ions contained in mitochondria by CaNa2EDTA. These results also indicate the possibility that Zn ions may regulate physiologically the level of serotonin and norepinephrine content in brain by inhibiting a MAO-A activity.

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  • Changes of materials that scavenge 1,1-diphenyl-2-picrylhydrazyl radicals in plasma by per-oral administration of Kampo medicine, Ninjin-yoei-to in rats. International journal

    Toru Egashira, Fusako Takayama, Yasuhiro Komatsu

    The Journal of pharmacy and pharmacology   55 ( 3 )   367 - 71   2003.3

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    The Kampo medicine, Ninjin-yoei-to, scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals in a dose-dependent fashion as did ascorbic acid and alpha-tocopherol. Ninjin-yoei-to, which is composed of 12 herbs, had a potent DPPH radical scavenging ability. We investigated the transition of the materials that scavenge DPPH radicals in plasma after oral administration of Ninjin-yoei-to to rats. When 1.0 g kg(-1) Ninjin-yoei-to was administered, the DPPH radical scavenging ability increased at 30 min and biphasic peaks were observed at 2 h and at 10 h. From the response-time profile, kinetic parameters including values for K(a) (absorption rate constant), t(max) (peak concentration time), t(1/2) (half-life) and MRT (mean residence time) of the radical scavenging ability in plasma could be calculated for DPPH radicals. K(a) values were 0.53 +/- 0.03 and 0.36 +/- 0.07 h, t(max) values were 2.1 +/- 1.04 and 8.56 +/- 2.69 h, t(1/2) values were 1.60 +/- 0.12 and 3.39 +/- 1.72 h, and MRT values were 4.14 +/- 1.59 and 8.18 +/- 2.55 h, respectively. These parameters calculated from the antioxidation dynamics were considered to offer a very meaningful procedure for examining the effects of Ninjin-yoei-to.

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  • Inhibition by Zn(2+) of A-form monoamine oxidase in monkey brain mitochondria.

    Toru Egashira, Fusako Takayama, Kumiko Sakai

    Journal of pharmacological sciences   91 ( 3 )   239 - 45   2003.3

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    The effects of ZnSO(4) on mitochondrial monoamine oxidase (MAO) activity in monkey brain were compared with those in rat and rabbit, in vitro. After preincubation at 25 degrees C for 20 min with 1 microM ZnSO(4), MAO-A activity in monkey brain was about 50% using serotonin (5-HT) as a substrate, and the inhibition was proportional to the concentration of ZnSO(4). However, ZnSO(4) had no effect on MAO-B activity in monkey brain using beta-phenylethylamine (beta-PEA) as a substrate. The inhibition by ZnSO(4) of MAO-A activity was competitive and reversible. CdSO(4) also inhibits MAO-A, but not MAO-B in monkey brain mitochondria. ZnSO(4) did not inhibit either MAO-A or MAO-B activity in rat and rabbit brain mitochondria. These results indicate that the inhibiting action of Zn(2+) differs depending on animal species. In monkey brain mitochondria, MAO-A was highly sensitive to Zn(2+) and MAO-B was less sensitive. These results also suggest that Zn(2+) may regulate the level of catecholamine content in monkey brain.

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  • Effects of zinc ion on type A monoamine oxidase in monkey brain mitochondria. International journal

    Toru Egashira, Fusako Takayama, Kumiko Sakai

    Biochemical pharmacology   65 ( 4 )   625 - 7   2003.2

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    The effects of ZnSO(4) on types A and B monoamine oxidase (MAO) isozymes in monkey brain mitochondria were investigated, in vitro. Type A MAO activity in monkey brain decreased to about 50% with 1 microM ZnSO(4) using serotonin as a substrate, and this inhibition was proportional to the concentration of ZnSO(4). ZnSO(4) had no effect, however, on type B MAO activity in monkey brain using beta-phenylethylamine as a substrate. The inhibition by ZnSO(4) of type A MAO activity was competitive and reversible. ZnSO(4) did not inhibit either type A or type B MAO activity in rat brain mitochondria. Almost similar results were also obtained when ZnCl(2) was used, in vitro. These results indicate that the inhibiting action of zinc ion differs depending on animal species and organ. Type A MAO in monkey brain mitochondria was highly sensitive to zinc ion, while type B activity was less sensitive.

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  • [Free radicals and oxidative stress: targeted ESR measurement of free radicals].

    Toru Egashira, Fusako Takayama

    Nihon yakurigaku zasshi. Folia pharmacologica Japonica   120 ( 4 )   229 - 36   2002.10

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    The detection of free radicals generated within the body may contribute to clarifying the pathophysiological role of free radicals in disease processes. As an appropriate procedure to examine the generation of free radicals in a biological system, electron spin resonance (ESR) has emerged as a powerful tool for detection and identification. A method for determination of oxygen radical scavenging activity using ESR and the spin trapping technique was developed. Oxygen radicals were trapped by 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) or alpha-phenyl-N-t-butylnitrone (PBN), and the DMPO or PBN spin adduct signal was measured quantitatively by an ESR spectrometer. The spin trapping method using ESR has also been reported for not only in vitro and ex vivo measurements but also in vivo measurements. In in vivo ESR, nitroxyl radical is being used as a spin trap well. ESR signal intensities of nitroxyl radical are measured after administration to animals and the signal decay rates of nitroxyl radical have reported to be influenced by various types of oxidative stress. With this method, it is possible to specify the type of radical or the location at which the free radicals are produced. The spin trapping method by in vivo ESR is an effective procedure for giving non-invasive measurements in animals. ESR imaging in the organs of live animals can also be obtained after injection of nitroxyl radicals as an imaging agent using ESR-computed tomography. In vivo ESR imaging has been established as a powerful technique for determining the spatial distribution of free radicals in living organs and tissues.

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  • Change in free radical-related substances in plasma following ischemia-reperfusion in rat liver. International journal

    Atsuko Iwamoto, Toru Egashira, Fusako Takayama, Yasumitsu Yamanaka, Takayuki Noguchi

    Pathophysiology : the official journal of the International Society for Pathophysiology   8 ( 3 )   167 - 174   2002.6

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    In order to clarify the relationship between free radicals and liver injury due to ischemia-reperfusion, we investigated the dynamics of radical-related substances in the blood of rats after liver ischemia-reperfusion. Subsequent to 60 min of liver ischemia, the generation of reactive oxygen species (ROS) from polymorphonuclear leukocytes (PMNs) initiated by phorbol myristate acetate (PMA) and lipid peroxidation significantly increased 2 h after reperfusion and showed peak values at 8-10 h. These values returned to the control level 32 h after reperfusion. The levels of nitric oxide metabolites (NO(x), NO(2)(-)+NO(3)(-)) increased biphasically at 10 and 32 h during the period of reperfusion, but did not return to control levels. Cu,Zn-superoxide dismutase (SOD) levels increased immediately after 5 min of reperfusion and showed a peak value after 20 min. This increase diminished gradually and returned to the control level 10 h after reperfusion. Mn-SOD increased 2 h after reperfusion, and this level was maintained for 48 h. The levels did not show increases at the end of ischemia and were nearly identical to the pre-ischemia levels. These finding obtained from the dynamics of radical-related substances are considered very meaningful for investigating mechanisms in the pathogenesis of liver injury by ischemia-reperfusion, and are clinically important in liver transplantation.

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  • Protective effects of LipoPGE_1, prostagland in E_1 incorporated in lipid microspheres, against liver injury caused by ischemia-reperfusion

    EGASHIRA Toru, TAKAYAMA Fusako, KUDO Yoshikuni, YAMANAKA Yasumitsu

    Folia Pharmacologica Japonica   105 ( 2 )   77 - 86   1995.2

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    Effect of LipoPGE1 on liver injury caused by ischemia-reperfusion were compared with that of PGE1-CD, cyclodextrin clathrated PGE1, in rats. LipoPGE1 (10μg/kg) and PGE1-CD (10μg/kg) were gradually injected into the portal vein 5 min both prior to ischemia and prior to reperfusion. In only the group receiving injections of vehicle alone, rats died within 2 days after the episode of 90-min liver ischemia. The survival rate of all rats treated with LipoPGE1 was higher than that of rats who received vehicle alone, which indicates that LipoPGE1 pretherapy improved the survival of rats after liver ischemia-reperfusion. LipoPGE1 markedly suppressed elevations of GOT, GPT, and LDH, lipid peroxide and aromatic amino acid levels in the plasma caused by ischemiareperfusion of the liver. When animals were given a single dose of LipoPGE1 prior to reperfusion, LipoPGE1 also suppressed elevations of GOT, GPT, LDH and lipid peroxide levels caused by 30min of liver ischemia followed by 12-hr reperfusion. These suppressive effects with LipoPGE1 were stronger than those of PGE1-CD. These findings suggest that LipoPGE1 may have therapeutic applications in the treatment of hepatic injury.

    DOI: 10.1254/fpj.105.77

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Books

  • 「ストレス百科事典ー精神医学的・臨床心理的・社会心理的・社会経済的影響」

    丸善  2013 

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  • ストレス百科事典

    丸善  2010 

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MISC

  • 高脂肪食およびDHAエチルエステル添加高脂肪食摂取後の6-Hydroxy Dopamine投与による線条体Dopamine濃度低下に対する影響

    加太 英明, 山主 智子, 高山 房子, 万倉 三正, 三澤 嘉久, 対馬 忠広

    日本栄養・食糧学会大会講演要旨集   71回   206 - 206   2017.4

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  • 杜仲葉エキス成分による非アルコール性脂肪性肝炎(NASH)進行リスク低減機能

    藤原 由理, 高山 房子, 江頭 亨, 細尾 信悟, 杉万 直, 平田 哲也, 山口 康代, 山崎 寛生, 川崎 博己, 豊田 博, 渡邊 律子, 山主 智子, 加太 英明, 万倉 三正, 大倉 朋子, 近藤 史織, 吉野 真帆, 岡田 茂

    日本薬学会年会要旨集   137年会 ( 3 )   203 - 203   2017.3

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  • 非アルコール性脂肪性肝炎(NASH)病態下サルコペニア進展リスクに対する杜仲葉エキスの影響

    近藤 史織, 高山 房子, 細尾 信悟, 杉万 直, 平田 哲也, 山口 康代, 山崎 寛生, 川崎 博己, 豊田 博, 渡邊 律子, 山主 智子, 加太 英明, 万倉 三正, 大倉 朋子, 藤原 由理, 吉野 真帆, 江頭 亨, 岡田 茂

    日本薬学会年会要旨集   137年会 ( 3 )   203 - 203   2017.3

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  • ニコチンはラット上頸神経節細胞の神経突起伸長を促進する(Nicotine enhances neurite outgrowth of rat primary cultured superior cervical ganglia cells)

    高取 真吾, 日野 隼人, 高山 房子, 北村 佳久, 千堂 年昭, 川崎 博己

    日本神経精神薬理学会年会プログラム・抄録集   46回   220 - 220   2016.7

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  • 非アルコール性肝炎(NASH)に対する杜仲葉エキスの予防機能

    高山 房子, 細尾 信悟, 平田 哲也, 山口 康代, 山崎 寛生, 和田 篤敬, 川崎 博己, 豊田 博, 渡邊 律子, 山主 智子, 加太 英明, 万倉 三正, 岡田 茂

    日本抗加齢医学会総会プログラム・抄録集   16回   227 - 227   2016.6

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  • 鬱血性心不全ラット洞房結節のカルシウム制御遺伝子発現異常に対するDHA経口摂取の影響

    山主 智子, 加太 英明, 小河 佳織, 高山 房子, 対馬 忠広, 三澤 嘉久, 万倉 三正

    日本栄養・食糧学会大会講演要旨集   70回   294 - 294   2016.4

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  • 高脂肪食摂取に伴う肝臓への脂質蓄積および活性酸素処理機能に対するDHAエチルエステルの影響

    加太 英明, 片山 真紗子, 山主 智子, 高山 房子, 万倉 三正, 三澤 嘉久, 対馬 忠広

    日本栄養・食糧学会大会講演要旨集   70回   203 - 203   2016.4

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  • Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries

    Panot Tangsucharit, Shingo Takatori, Yoshito Zamami, Mitsuhiro Goda, Poungrat Pakdeechote, Hiromu Kawasaki, Fusako Takayama

    JOURNAL OF PHARMACOLOGICAL SCIENCES   130 ( 1 )   24 - 32   2016.1

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    The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR) subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol) produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol) disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist) or 4-DAMP (M1 and M3 antagonist) plus hexamethonium (nicotinic AChR antagonist), but not methoctramine (M2 and M4 antagonist). These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation. (C) 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V.

    DOI: 10.1016/j.jphs.2015.12.005

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  • ラット上頚神経節細胞からの神経突起に及ぼすニコチンの影響

    高取真吾, 日野隼人, 高山房子, 川崎博己

    日本薬理学会西南部会プログラム/抄録集   69th   73   2016

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  • Nicotine facilitates reinnervation of phenol-injured perivascular adrenergic nerves in the rat mesenteric resistance artery International journal

    Shingo Takatori, Hidetoshi Fujiwara, Kenta Hagimori, Narumi Hashikawa-Hobara, Ayako Yokomizo, Fusako Takayama, Panot Tangsucharit, Nobufumi Ono, Hiromu Kawasaki

    EUROPEAN JOURNAL OF PHARMACOLOGY   748   1 - 9   2015.2

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    Nicotine has been shown to have neuroprotective and neurotrophic actions in the central nervous system. To elucidate the peripheral neurotrophic effects of nicotine, we determined whether nicotine affected the reinnervation of mesenteric perivascular nerves following a topical phenol treatment. A topical phenol treatment was applied to the superior mesenteric artery proximal to the abdominal aorta in Wistar rats. We examined the immunohistochemistry of the distal small arteries 7 days after the treatment. The topical phenol treatment markedly reduced the density of tyrosine hydroxylase (TH)-LI and calcitonin gene-related peptide (CGRP)-LI fibers in these arteries. The administration of nicotine at a dose of 3 mg/kg/day (1.5 mg/kg/injection, twice a clay), but not once a day or its continuous infusion using a mini-pump significantly increased the density of TH-LI nerves without affecting CGRP-Ll nerves. A pretreatment with nicotinic acetylcholine receptor antagonists hexamethonium, mecamylamine, and methyllycaconitine, but not dextrometorphan, canceled the TH-LI nerve reinnervation induced by nicotine. Nicotine significantly increased NGF levels in the superior cervical ganglia (SCG) and mesenteric arteries, but not in the dorsal root ganglia, and also up-regulated the expression of NGF receptors (TrkA) in the SCG, which were canceled by hexamethonium. These results suggested that nicotine exhibited neurotrophic effects that facilitated the reinnervation of adrenergic TH-LI nerves by activating alpha 7 nicotinic acetylcholine receptor and NGF in the SCG. (C) 2014 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ejphar.2014.12.005

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  • 症状改善薬投与に伴うパーキンソン病モデルマウスの病態進行に及ぼすスクアレンの影響 抗酸化活性への影響

    加太 英明, 山主 智子, 照屋 茜, 問田 真由, 香川 穂輝, 高山 房子, 万倉 三正

    日本栄養・食糧学会大会講演要旨集   68回   265 - 265   2014.4

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  • Oral Administration of EPA or DHA Modifies Cardiac Function and Ameliorates Congestive Heart Failure in Male Rats. "jointly worked"

    Hideaki Kabuto, Tomoko T. Yamanushi, Najma Janjua, Fusako Takayama, Mitsumasa Mankura

    The Journal of Nutrition   144 ( 4 )   467 - 474   2014

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  • 高純度エイコサペンタエン酸及びドコサヘキサエン酸経口投与によるラット右鬱血性心不全の予防効果

    山主 智子, 加太 英明, 平川 栄一郎, Janjua Najma, 高山 房子, 万倉 三正

    日本栄養・食糧学会大会講演要旨集   67回   116 - 116   2013.4

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  • Fermented papaya preparation halts the progression of non-alcoholic steatohepatitis in rats

    Shinki Murakami, Fusako Takayama, Toru Egashira, Mitsuko Imao, Akitane Mori

    Journal of Biophysical Chemistry   4 ( 2 )   84 - 90   2013

  • Nicotine facilitates the reinnervation of injured perivascular nerves

    Kenta Hagimori, Hidetoshi Fujiwara, Tangsucharit Panot, Hiromu Kawasaki, Fusako Takayama

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   194P - 194P   2013

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  • Do cholinergic nerves innervating rat mesenteric arteries regulate vascular tone? International journal

    Panot Tangsucharit, Shingo Takatori, Pengyuan Sun, Yoshito Zamami, Mitsuhiro Goda, Poungrat Pakdeechote, Fusako Takayama, Hiromu Kawasaki

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY   303 ( 11 )   R1147 - R1156   2012.12

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    Tangsucharit P, Takatori S, Sun P, Zamami Y, Goda M, Pakdeechote P, Takayama F, Kawasaki H. Do cholinergic nerves innervating rat mesenteric arteries regulate vascular tone? Am J Physiol Regul Integr Comp Physiol 303: R1147-R1156, 2012. First published October 10, 2012; doi:10.1152/ajpregu.00317.2012.-Vascular blood vessels have various types of cholinergic acetylcholine receptors (AChR), but the source of ACh has not been confirmed. Perivascular adrenergic nerves and nonadrenergic calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerves innervate rat mesenteric arteries and regulate vascular tone. However, function of cholinergic innervation remains unknown. The present study investigated cholinergic innervation by examining effects of cholinesterase inhibitor (neostigmine), a muscarinic AChR antagonist (atropine), and a nicotinic AChR antagonist (hexamethonium) on adrenergic nerve-mediated vasoconstriction and CGRPergic nerve-mediated vasodilation in rat mesenteric vascular beds without endothelium. In preparations treated with capsaicin (CGRP depletor) or in the presence of N-omega-nitro-L-arginine methyl ester (nonselective nitric oxide synthase inhibitor), perivascular nerve stimulation (PNS; 2-12 Hz) evoked a frequency-dependent vasoconstriction. In the same preparations, exogenous norepinephrine induced a concentration-dependent vasoconstriction. Atropine, hexamethonium, and neostigmine had no effect on vasoconstrictor responses to PNS and norepinephrine injections. In denuded preparations, these cholinergic agents did not affect the PNS (12 Hz)-evoked release of norepinephrine in perfusate. In preconstricted preparations without endothelium in the presence of guanethidine (adrenergic neuron blocker), PNS (1-4 Hz) induced a frequency-dependent vasodilation, which was not affected by atropine, hexamethonium, and neostigmine. In denuded preparations treated with capsaicin and guanethidine, PNS did not induce vascular responses, and atropine, neostigmine, and physostigmine had no effect on PNS. Immunohistochemistry study showed choline acetyltransferase-immunopositive fibers, which were resistant to capsaicin and 6-hydroxy-dopamine (adrenergic toxin). These results suggest that rat mesenteric arteries have cholinergic innervation, which is different from adrenergic and capsaicin-sensitive nerves and not associated with vascular tone regulation.

    DOI: 10.1152/ajpregu.00317.2012

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  • Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis

    Wing Pak, Fusako Takayama, Manaka Mine, Kazuo Nakamoto, Yasumasa Kodo, Mitsumasa Mankura, Toru Egashira, Hiromu Kawasaki, Akitane Mori

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   51 ( 3 )   227 - 234   2012.11

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    The pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, but accumulating data suggest oxidative stress and the relationship between inflammation and immunity plays a crucial role. The aim of this study is to investigate the spirulina, which is a blue-green algae rich in proteins and other nutritional elements, and its component-phycocyanin effect on a rat model of NASH. NASH model rats were established by feeding male Wistar rats with choline-deficient high-fat diet (CDHF) and intermittent hypoxemia by sodium nitrite challenge after 5 weeks of CDHF. After experimental period of 10 weeks, blood and liver were collected to determine oxidative stress injuries and efficacies of spirulina or phycocyanin on NASH model rats. In the NASH model rats, increase in plasma liver enzymes and liver fibrosis, increases in productions of reactive oxygen species from liver mitochondria and from leukocytes, the activation of nuclear factor-kappa B, and the change in the lymphocyte surface antigen ratio (CD4(+)/CD8(+)) were observed. The spirulina and phycocyanin administration significantly abated these changes. The spirulina or phycocyanin administration to model rats of NASH might lessen the inflammatory response through anti-oxidative and anti-inflammatory mechanisms, breaking the crosstalk between oxidative stress and inflammation, and effectively inhibit NASH progression.

    DOI: 10.3164/jcbn.12-18

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  • ラット腸間膜動脈血管周囲神経損傷モデルにおけるnicotineの神経再分布促進作用

    萩森健太, 藤原秀敏, 高取真吾, 高山房子, 川崎博已

    日本薬学会年会要旨集   132nd ( 3 )   84   2012.3

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  • M1/M3 acetylcholine receptors mediate acetylcholine-induced endothelium-independent and cgrpergic nerve-mediated vasodilation in rat mesenteric arteries

    Panot Tangsucharit, Poungrat Pakdeechote, Shingo Takatori, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   118   78P - 78P   2012

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  • 高純度エイコサペンタエン酸及びドコサヘキサエン酸投与によるラット炎症性肺高血圧症予防効果

    山主 智子, 加太 英明, 平川 栄一郎, ジャンジュア・ナジマ, 高山 房子, 万倉 三正

    脂質栄養学   20 ( 2 )   161 - 161   2011.8

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  • パーキンソン病モデルマウスの脳内ドーパミン低下に及ぼすスクアレンおよびスクアランの影響

    加太 英明, 山主 智子, 万倉 三正, 高山 房子

    日本栄養・食糧学会大会講演要旨集   65回   140 - 140   2011.4

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  • NASHをターゲットとする食品の開発 -スピルリナを中心に-

    高山房子, 中本賀寿夫, 峰麻奈加, 杉本志保, 白穎, 江頭亨, 川崎博巳, 黄堂泰昌, 万倉三正, 岡田茂, 森昭胤

    臨床化学   40 ( 4 )   333 - 340   2011

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  • Effects of Docosahexaenoic Acid in an Experimental Rat Model of Nonalcoholic Steatohepatitis

    Fusako Takayama, Kazuo Nakamoto, Nagao Totani, Tomoko Yamanushi, Hideaki Kabuto, Takao Kaneyuki, Mitsumasa Mankura

    JOURNAL OF OLEO SCIENCE   59 ( 8 )   407 - 414   2010.8

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    Docosahexaenoic acid (DHA) regulates the lipid metabolism and inflammation that is closely associated with oxidative stress. The present study investigated the effects of DHA on the development of nonalcoholic steatohepatitis (NASH). To induce fatty liver, rats were fed choline-deficient high-fat diets (CDHF). The rats were then divided into 4 groups treated over the subsequent 6 weeks as follows: control, CDHF, CDHF + oxidative stress (NASH), and NASH + DHA (1.0 g/kg, p.o.). Rats of the control group were fed NW chow diet only. NASH rats showed severe steatohepatitis and liver fibrosis. Treatment with DHA significantly decreased the n-6/n-3 ratio in the livers and increased plasma SOD like activity compared with NASH rats. In addition, DHA attenuated the liver fibrosis during NASH development. Therefore, a higher DHA ratio in the liver of NASH rats might regulate the inflammatory response through a low n-6 ratio and diminished oxidative stress, effectively inhibiting liver fibrosis during NASH progression. These results suggested that DHA is a novel functional food for the prevention of NASH.

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  • 症状改善薬投与に伴うパーキンソン病モデルマウスの行動異常・病態進行に及ぼす香辛料成分の影響

    加太 英明, 山主 智子, 高山 房子, 万倉 三正

    日本栄養・食糧学会大会講演要旨集   64回   124 - 124   2010.5

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  • 高純度エイコサペンタエン酸及びドコサヘキサエン酸経口投与によるラット心臓機能の変化

    山主 智子, 加太 英明, ジャンジュア・ナジマ, 高山 房子, 万倉 三正

    日本栄養・食糧学会大会講演要旨集   64回   131 - 131   2010.5

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  • 非アルコール性脂肪性肝炎モデルに対する大豆ペプチドとDHAの有効性に関する研究

    杉本 志保, 万倉 三正, 江頭 亨, 三宅 夏樹, 川崎 博己, 高山 房子

    日本薬学会年会要旨集   130年会 ( 3 )   218 - 218   2010.3

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  • DHA 製品の開発と機能性評価

    万倉三正, 西岡功志, 加太英明, 山主智子, 戸谷永生, 中本賀寿夫, 金行孝雄, 高山房子

    ジャパンフードサイエンス   49 ( 1 )   45 - 52   2010

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  • Water extract of Vitis coignetiae grape leaves attenuates oxidative stress and inflammation in progressive NASH rats

    Azusa Hasegawa, Fusako Takayama, Hiromu Kawasaki, Toru Egashira, Mitsumasa Mankura, Shigeru Okada, Akitane Mori

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112   208P - 208P   2010

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  • A novel animal model of nonalcoholic steatohepatitis (NASH): Hypoxemia enhances the development of NASH

    Fusako Takayama, Toru Egashira, Hiromu Kawasaki, Mitsumasa Mankura, Kazuo Nakamoto, Shigeru Okada, Akitane Mori

    Journal of Clinical Biochemistry and Nutrition   45 ( 3 )   335 - 340   2009.11

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    Recent reports described a high incidence of nonalcoholic steatohepatitis (NASH) in patients with obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans. Chemical hypoxemia through methemoglobinemia was induced by daily intraperitoneal injection of sodium nitrite (40 mg/kg) for 4 weeks in rats with fatty liver. The later was induced by 4-week feeding a choline-deficient high-fat diet (CDHF). Besides, the normal chow diets feeding groups were prepared with in the same manner except for CDHF feeding. The animal experiment was performed in four groups
    Normal control, Hypoxemia, CDHF, and CDHF + hypoxemia. Nitrite was given for the later 4 weeks to each rat of Hypoxemia and CDHF + hypoxemia. CDHF + hypoxemia rats were confirmed to develop histological changes that resemble those of patients with NASH, together with biochemical liver dysfunction, while CDHF group was limited in mild steatosis, and Hypoxemia group liver was normal. Present study established a reproducible and useful NASH model resembling the main features of NASH in humans, and showed first that recurrent and intermittent hypoxemia aggravate fatty liver to steatohepatitis and liver fibrosis.

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  • Beneficial Effects of Fermented Green Tea Extract in a Rat Model of Non-alcoholic Steatohepatitis

    Kazuo Nakamoto, Fusako Takayama, Mitsumasa Mankura, Yuki Hidaka, Toru Egashira, Tetsuya Ogino, Hiromu Kawasaki, Akitane Mori

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   44 ( 3 )   239 - 246   2009.5

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    Oxidative stress is frequently considered as a central mechanism of hepatocellular injury in non-alcoholic steatohepatitis (NASH). The aim of this study was to investigate the effects of fermented green tea extracts (FGTE) on NASH. Rats were fed a choline-deficient high-fat diet for 4 weeks to nutritionally generate fatty livers. NASH was induced chemically by oxidative stress using repeated intraperitoneal injections of nitrite. Rats with NASH developed steatohepatitis and liver fibrosis after 6-week of such treatment. At 10 weeks, blood and liver samples were collected from anesthetized animals and assessed for extent of OS injury and effects of FGTE, by biochemical, histological and histochemical analyses. FGTE reduced serum levels of liver enzymes, lipid peroxidation and production of mitochondrial reactive oxygen species. In addition, FGTE showed inhibition of progressions of cirrhosis. Our findings suggest that our FETE have strong radical scavenging activity and may be beneficial in the prevention of NASH progression.

    DOI: 10.3164/jcbn.08-256

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  • 非アルコール性脂肪性肝炎(NASH)に対するDHAの効果に関する研究

    金行 孝雄, 高山 房子, 川崎 博巳, 戸谷 永生, 中本 賀寿夫, 万倉 三正, 森 昭胤

    日本栄養・食糧学会大会講演要旨集   63回   96 - 96   2009.5

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  • Beneficial Effects of Vitis coignetiae Pulliat Leaves on Nonalcoholic Steatohepatitis in a Rat Model

    Fusako Takayama, Kazuo Nakamoto, Hiromu Kawasaki, Mitsumasa Mankura, Toru Egashira, Keiji Ueki, Azusa Hasegawa, Shigeru Okada, Akitane Mori

    ACTA MEDICA OKAYAMA   63 ( 2 )   105 - 111   2009.4

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    Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on the abundant polyphenols and anthocyanins in its fruit. However, it is not known whether the leaves of this plant confer similar benefits. This study investigated the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH). Rats were fed a choline-deficient high-fat diet for four weeks to generate fatty livers. NASH was induced by oxidative stress loading. Ten weeks later, blood and liver samples were collected from anesthetized animals and assessed biochemically, histologically, and histochemically to determine the extent of oxidative stress injury and the overall effects of VCPL. Six-week VCPL extract supplementation reduced serum levels of liver enzymes, decreased CYP2E1 induction, increased plasma antioxidant activities and delayed the progression of liver fibrosis. The findings suggested that VCPL has strong radical-scavenging activity and may be beneficial in preventing NASH progression.

    DOI: 10.18926/AMO/31835

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  • マウス腸間膜動脈血管床灌流標本における血管周囲神経を介する反応

    藤原 弘喜, 和家 祥大, 高山 房子, 北村 佳久, 川崎 博己

    日本薬理学雑誌   133 ( 3 )   26P - 26P   2009.3

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  • アンモニア誘発性脳浮腫発症のメカニズムPathogenetic mechanisms of ammonia-induced brain edema

    高山 房子, 森 昭胤TAKAYAMA Fusako, MORI Akitane

    腎と透析   67 ( 1 )   75 - 79   2009

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  • Anti-oxidative and anti-inflammatory effects of spirulina and its component on non-alcoholic steatohepatitis model rats

    Pak Wing, Fusako Takayama, Mitsumasa Mankura, Toru Egashira, Yasumasa Kodo, Akitane Mori

    FREE RADICAL BIOLOGY AND MEDICINE   47   S164 - S164   2009

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  • Protective Effect of SAIDO-PS501 on Stress-induced Acute Gastric Mucosal Lesion in Rats

    Shinki Murakami, Fusako Takayama, Toru Egashira, Mitsumasa Mankura, Mitsuko Imao, Hiromu Kawasaki, Shigeru Okada, Akitane Mori

    FREE RADICAL BIOLOGY AND MEDICINE   47   S131 - S132   2009

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  • Vascular responses to periarterial nerve stimulation (PNS) in mouse mesenteric vascular beds

    Hiroki Fujiwara, Yoshihiro Wake, Fusako Takayama, Yoshihisa Kitamura, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   261P - 261P   2009

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  • Protective Effect of SAIDO-PS501 on Stress-induced Acute Gastric Mucosal Lesion in Rats

    Shinki Murakami, Fusako Takayama, Toru Egashira, Mitsumasa Mankura, Mitsuko Imao, Hiromu Kawasaki, Shigeru Okada, Akitane Mori

    FREE RADICAL BIOLOGY AND MEDICINE   47   S147 - S147   2009

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  • マウス腸間膜動脈灌流標本における血管反応性の解析

    和家祥大, 藤原弘喜, 高山房子, 北村佳久, 川崎博己

    日本循環薬理学会口演要旨集   19th   44   2009

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  • Anti-oxidative and Anti-inflammatory Effects of Oyster Preparation on NASH model rats

    Chengzhu Zhao, Fusako Takayama, Mitsumasa Mankura, Toru Egashira, Hiromu Kawasaki, Shigeru Okada, Akitane Mori

    FREE RADICAL BIOLOGY AND MEDICINE   47   S164 - S164   2009

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  • THE EFFECTS OF DHA FOR EXPERIMENTAL NASH MODEL RATS

    Takao Kaneyuki, Fusako Takayama, Nagao Totani, Mitsumasa Mankura, Akitane Mori

    ANNALS OF NUTRITION AND METABOLISM   55   401 - 401   2009

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  • Usefulness of Cancer Chemotherapy Adverse Effects Manual in Department of Urology, Okayama University Hospital

    TAMAKI Chihiro, NAWA Hideki, IHORIYA Akiko, SAIKA Takashi, WATANABE Toyohiko, SAGARA Hidenori, KAWASAKI Youichi, MATSUNAGA Hisashi, KAWASAKI Hiromu, TAKAYAMA Fusako, GOMITA Yutaka, KUMON Hiromi, KAWASAKI Hiromu

    Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences)   34 ( 10 )   962 - 971   2008.10

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    In cancer chemotherapy,adverse effects are inevitable and occasionally fatal.Also,the use of appropriate measures against them can greatly influence the QOL of cancer patients so such measures should be taken rapidly.To do this,an extensive knowledge base containing information on the degrees and time of occurrence of various anticancer drug adverse effects is necessary.<br>In this study,we developed an evidence-based adverse effects manual for doctors.Six months after distributing the manual,we examined its usefulness by administering a questionnaire.More than 80% of the doctors responding said that the manual saved work in deciding on a prescription or examining medical treatments and more than 90% of them thought that the manual aided them in administering treatment.In conclusion,our manual provides doctors with a useful tool that enabled them to rapidly administer appropriate treatment for adverse effects due to cancer chemotherapy.

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  • Nerve Growth Factor accelerate distribution of perivascular nerves in neovasculatures in mice

    GODA Mitsuhiro, ATAGI Saori, AMITANI Keisuke, KITAMURA Yoshihisa, TAKAYAMA Fusako, KAWASAKI Hiromu

    31 ( 3 )   91 - 96   2008.10

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  • 岡山大学病院泌尿器科におけるがん薬物療法副作用対策マニュアルの有用性

    玉木 千尋, 名和 秀起, 庵谷 亜希子, 雑賀 隆史, 渡邉 豊彦, 相良 英憲, 河崎 陽一, 松永 尚, 千堂 年昭, 高山 房子, 五味田 裕, 公文 裕巳, 川崎 博巳

    医療薬学   34 ( 10 )   962 - 971   2008.10

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    岡山大学病院泌尿器科におけるがん薬物療法副作用対策マニュアルの有用性について検討した。作成したマニュアルを病棟医師13例に配布した。6ヵ月後にアンケート調査を行い、13例より回答を得た。マニュアルの使用頻度は、週1回が30.8%、月2〜3回が30.8%、月1回が30.8%、ほとんど使わないが7.7%であった。マニュアル記載項目のなかで最も使用頻度の高い項目は、投与量・投与時間・投与スケジュール、腎障害時・肝障害時の抗がん剤減量目安、副作用モニタリングシート、米国臨床腫瘍学会で推奨されている制吐薬の組み合わせ方であった。マニュアルの有用性に関して具体的に質問して、各質問項目を4段階で評価した。それぞれで3-4の評価が8割を超えた。マニュアルが役に立つ点では、「重篤な副作用の回避」および「適切な治療の提供」が6割を超えた。

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J03520&link_issn=&doc_id=20081015410009&doc_link_id=%2Fdb5pharm%2F2008%2F003410%2F009%2F0962-0971%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdb5pharm%2F2008%2F003410%2F009%2F0962-0971%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 20-P1-139 肺移植患者における中枢神経副作用発症と免疫抑制薬との関連性調査(有害事象・副作用,来るべき時代への道を拓く)

    藤原 弘喜, 相良 英憲, 佐藤 智昭, 松永 尚, 千堂 年昭, 五味田 裕, 高山 房子, 川崎 博己

    日本医療薬学会年会講演要旨集   18   2008.9

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  • 岡山大学薬学部におけるPBL導入の現状と6年制に向けての課題

    岡崎宏美, 四宮一昭, 名倉弘哲, 北村佳久, 合葉哲也, 高山房子, 黒崎勇二, 川崎博己, 千堂年昭

    医療薬学フォーラム講演要旨集   16th   304   2008.7

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  • 台湾産の洛神花(Hibiscus sabadadariffa L)のin vitroにおける抗酸化について

    松下 至, 金行 孝雄, 村上 泰子, 中本 賀寿夫, 野田 泰子, 高山 房子, 万倉 三正, 森 昭胤

    日本栄養・食糧学会大会講演要旨集   62回   260 - 260   2008.4

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  • ラット腸間膜動脈血管の血管周囲交感神経を介するCGRP神経性血管弛緩反応におけるprotonの関与

    宮下智子, 平井和浩, 北村佳久, 高山房子, 川崎博己

    日本薬理学雑誌   131 ( 3 )   34P   2008.3

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  • Effect of postprandial hyperglycemia and hyperinsulinemia on vascular responsiveness

    Yoshito Zamami, Shingo Takatori, Yukiko Iwatani, Kousuke Yamawaki, Satoko Miyashita, Nana Yabumae, Fusako Takayama, Mitsunobu Mio, Hiromu Kawasaki

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN   128 ( 3 )   419 - 424   2008.3

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    Recent clinical studies demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin 11, calcitonin generelated peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentration of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting injection of pressor responses to noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nerve-mediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemic, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increases adrenergic nerve-mediated vasoconstriction, which is partly associated with the blunted CGRPergic nerve function, and that plasma insulin concentration associated with hyperglycemia may be responsible for alteration of neuronal vascular regulation.

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  • Effect of postprandial hyperglycemia and hyperinsulinemia on vascular responsiveness

    Yoshito Zamami, Shingo Takatori, Yukiko Iwatani, Kousuke Yamawaki, Satoko Miyashita, Nana Yabumae, Fusako Takayama, Mitsunobu Mio, Hiromu Kawasaki

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN   128 ( 3 )   419 - 424   2008.3

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    Recent clinical studies demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin 11, calcitonin generelated peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentration of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting injection of pressor responses to noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nerve-mediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemic, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increases adrenergic nerve-mediated vasoconstriction, which is partly associated with the blunted CGRPergic nerve function, and that plasma insulin concentration associated with hyperglycemia may be responsible for alteration of neuronal vascular regulation.

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  • ラット腸間膜動脈血管の血管周囲交感神経を介するCGRP神経性血管弛緩反応におけるprotonの関与

    宮下 智子, 平井 和浩, 北村 佳久, 高山 房子, 川崎 博己

    日本薬理学雑誌   131 ( 3 )   34p - 34p   2008.3

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  • 腎性高血圧ラット腸間膜動脈における血管周囲一酸化窒素含有神経機能変化

    小山 敏広, 庄司 知世, 畑中 由香子, 合田 光寛, 芳原 成美, 高山 房子, 川崎 博己

    日本薬理学雑誌   131 ( 3 )   25p - 25p   2008.3

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  • 若手薬理研究者が展開する病態解明と薬効評価による創薬へのアプローチ 領域を超えた交流から広がる創薬への道 腎血管性高血圧ラット腸間膜動脈における血管周囲一酸化窒素含有神経の機能変化

    小山 敏広, 畑中 由香子, 合田 光寛, 芳原 成美, 高山 房子, 川崎 博己

    日本薬学会年会要旨集   128年会 ( 1 )   249 - 249   2008.3

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  • 光に不安定な薬剤の簡易懸濁法を用いた経管投与方法について

    座間味 義人, 槙田 崇志, 安藤 哲信, 倉田 なおみ, 合葉 哲也, 黒崎 勇二, 北村 佳久, 千堂 年昭, 高山 房子, 川崎 博己, 五味田 裕

    日本薬学会年会要旨集   128年会 ( 4 )   220 - 220   2008.3

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  • フルクトース負荷インスリン抵抗性モデルラットの負荷早期における神経性血管反応性の変化

    座間味 義人, 高取 真吾, 薮前 奈々, 宮下 智子, 細田 美穂, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬理学雑誌   131 ( 3 )   40p - 40p   2008.3

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  • 新しい薬効評価法を用いた治療薬の開発 食後高血糖が血管反応性に及ぼす影響

    座間味 義人, 高取 真吾, 岩谷 有希子, 山脇 康佑, 宮下 智子, 薮前 奈々, 高山 房子, 見尾 光庸, 川崎 博己

    薬学雑誌   128 ( 3 )   419 - 424   2008.3

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  • フルクトース負荷インスリン抵抗性モデルラットの負荷早期における神経性血管反応性の変化

    座間味 義人, 高取 真吾, 薮前 奈々, 宮下 智子, 細田 美穂, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬理学雑誌   131 ( 3 )   40p - 40p   2008.3

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  • 無麻酔無拘束ラットにおけるClonidineによる中枢性昇圧反応の発現機序に関する脳内GABA神経系の関与

    花房伸幸, 岡本和明, 北村佳久, 高山房子, 川崎博己

    血管   31 ( 1 )   41   2008.1

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  • Nerve Growth Factor(NGF)は新生血管における血管周囲神経の分布を促進させる

    合田光寛, 能木沙織, 網谷慶介, 芳原成美, 北村佳久, 高山房子, 川崎博己

    血管   31 ( 1 )   29   2008.1

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  • マウス正常微小血管および新生血管における血管周囲神経の分布

    合田光寛, 能木沙織, 網谷慶介, 芳原成美, 北村佳久, 高山房子, 川崎博己

    日本薬理学雑誌   131 ( 1 )   10P   2008.1

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  • Nerve Growth Factor(NGF)は新生血管における血管周囲神経の分布を促進させる

    合田 光寛, 能木 沙織, 網谷 慶介, 芳原 成美, 北村 佳久, 高山 房子, 川崎 博己

    血管   31 ( 1 )   29 - 29   2008.1

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  • マウス正常微小血管および新生血管における血管周囲神経の分布

    合田 光寛, 能木 沙織, 網谷 慶介, 芳原 成美, 北村 佳久, 高山 房子, 川崎 博己

    日本薬理学雑誌   131 ( 1 )   10P - 10P   2008.1

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  • 食後高血糖時の急性高インスリン状態における交感神経機能亢進とAngiotensin II Type 1受容体の関与

    座間味 義人, 高取 真吾, 宮下 智子, 薮前 奈々, 細田 美穂, 岩谷 有希子, 高山 房子, 見尾 光庸, 川崎 博己

    血管   31 ( 1 )   38 - 38   2008.1

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  • マウス腸間膜動脈血管床灌流標本における血管周囲神経を介する反応

    藤原弘喜, 和家祥大, 高山房子, 北村佳久, 川崎博己

    日本薬理学会近畿部会プログラム・要旨集   114th   46   2008

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  • Distribution and characterization of perivascular nerves in neovasculatures of mice

    Mitsuhiro Goda, Saori Atagi, Keisuke Amitani, Narumi Hobara, Yoshihisa Kitamura, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   113P - 113P   2008

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  • Proton-related interaction between perivascular nerves in the rat mesenteric artery

    Satoko Miyashita, Kazuhiro Hirai, Yoshihisa Kitamura, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   196P - 196P   2008

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  • Preventive Effect on FGTE Against An Experimental NASH Model Rats

    Kazuo Nakamoto, Fusako Takayama, Mitsumasa Mankura, Hiromu Kawasaki, Tetsuya Ogino, Kozo Utsumi, Akitane Mori

    FREE RADICAL BIOLOGY AND MEDICINE   45   S128 - S128   2008

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  • Changes in mesenteric perivascular nerve function in fructose-drinking rats (FDR)

    Nana Yabumae, Miho Hosoda, Yoshito Zamami, Hiroki Fujiwara, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   195P - 195P   2008

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  • Effect of SAIDO-PS501 on Non-Alcoholic Steatohepatitis

    Shinki Murakami, Fusako Takayama, Kazuo Nakamoto, Mitsumasa Mankura, Toru Egashira, Mitsuko Imao, Hiromu Kawasaki, Shigeru Okada, Akitane Mori

    FREE RADICAL BIOLOGY AND MEDICINE   45   S88 - S89   2008

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  • Involvement of GABAergic nerves in pressor response to microinjection of Clonidine in conscious rats

    Nobuyuki Hanafusa, Kazuaki Okamoto, Yoshihisa Kitamura, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   238P - 238P   2008

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  • Effect of the Fermented Green Tea on Body-Fat Accumulation in Rats Fed a High Fat Diet

    Yuki Hidaka, Fusako Takayama, Kazuo Nakamoto, Hiromu Kawasaki, Toru Egashira, Mitsumasa Mankura, Akitane Mori

    FREE RADICAL BIOLOGY AND MEDICINE   45   S126 - S126   2008

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  • Effect of Spirulina on Experimental Non-Alcoholic Steatohepatitis Model Rats

    Pak Wing, Fusako Takayama, Mitsumasa Mankura, Toru Egashira, Yasumasa Kodo, Akitane Mori

    FREE RADICAL BIOLOGY AND MEDICINE   45   S130 - S130   2008

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  • Acute hyperglycemia and hyperinsulinemia enhance adrenergic vasoconstriction and decrease calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats

    ZAMAMI Yoshito, TAKATORI Shingo, YAMAWAKI Kousuke, MIYASHITA Satoko, YABUMAE Nana, TAKAYAMA Fusako, MIO Mitsunobu, KAWASAKI Hiromu

    血管   30 ( 3 )   81 - 86   2007.10

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  • 正常微小血管および新生血管における血管周囲神経の分布に関する研究

    合田光寛, 能木沙織, 網谷慶介, 芳原成美, 北村佳久, 高山房子, 川崎博己

    生体機能と創薬シンポジウム   2007   148 - 149   2007.9

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  • 29-P2-191 アンプル開封時における抗がん剤曝露の危険性 : 5-FUアンプルカット前の静置時間の影響(製剤,社会の期待に応える医療薬学を)

    藪前 奈々, 河崎 陽一, 松香 直行, 横山 紀子, 川島 理恵子, 岡田 健男, 上島 智, 北村 佳久, 千堂 年昭, 高山 房子, 五味田 裕, 川崎 博己

    日本医療薬学会年会講演要旨集   17   2007.9

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  • 29-P2-115 がん化学療法副作用対策マニュアルの有用性(リスクマネジメント,社会の期待に応える医療薬学を)

    玉木 千尋, 名和 秀起, 庵谷 亜希子, 相良 英憲, 河崎 陽一, 松永 尚, 千堂 年昭, 高山 房子, 五味田 裕, 川崎 博已

    日本医療薬学会年会講演要旨集   17   2007.9

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  • 30-P3-50 アミオダロンとワルファリンカリウムの相互作用 : アミオダロン併用時におけるワルファリン投与量の調節(相互作用,社会の期待に応える医療薬学を)

    花房 伸幸, 森 英樹, 千堂 年昭, 高山 房子, 五味田 裕, 川崎 博己, 出石 文男

    日本医療薬学会年会講演要旨集   17   2007.9

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  • 30-P2-12 大量がん化学療法における悪心・嘔吐対策(副作用・有害事象,社会の期待に応える医療薬学を)

    宮下 智子, 岡崎 宏美, 末包 幸恵, 虫明 智恵子, 大野 さとみ, 津田 真美, 三宅 伸子, 千堂 年昭, 高山 房子, 五味田 裕, 川崎 博己

    日本医療薬学会年会講演要旨集   17   2007.9

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  • フルクトース負荷早期における血管反応性の変化

    薮前 奈々, 細田 美穂, 座間味 義人, 金 きょう, 合田 光寛, 小山 敏広, 高取 真吾, 高山 房子, 川崎 博己

    日本薬理学雑誌   130 ( 3 )   12P - 12P   2007.9

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  • フルクトース負荷早期における血管反応性の変化

    薮前 奈々, 細田 美穂, 座間味 義人, 金 きょう, 合田 光寛, 小山 敏広, 高取 真吾, 高山 房子, 川崎 博己

    日本薬理学雑誌   130 ( 3 )   12P - 12P   2007.9

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  • ESRラジカル計測によるBio-Dosimetryへの試み 砂糖、ナイロン、歯牙、毛髪や爪etc.で放射線が測れる?

    西村 明久, 荒尾 信一, 板谷 道信, 村中 明, 松宮 昭, 梶原 康正, 今城 吉成, 平塚 純一, 久保田 壽一, 小野 俊朗, 高山 房子

    Radiation Medicine   25 ( Suppl.I )   101 - 101   2007.4

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  • ラット腸間膜動脈血管の内皮細胞除去後におけるcAMP及びcGMP量の変化

    岩谷 有希子, 能木 沙織, 沼 裕美, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬学会年会要旨集   127年会 ( 2 )   142 - 142   2007.3

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  • 新しい薬効評価法を用いた治療薬の開発 食後高血糖が血管反応性に及ぼす影響

    座間味 義人, 高取 真吾, 山脇 康佑, 宮下 智子, 藪前 奈々, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬学会年会要旨集   127年会 ( 1 )   291 - 291   2007.3

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  • フルクトース負荷ラットのインスリン抵抗性に及ぼすプロポリス長期投与の影響

    小山 敏広, 土井 志真, 高取 真吾, 座間味 義人, 合田 光寛, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬学会年会要旨集   127年会 ( 2 )   133 - 133   2007.3

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  • マウス腫瘍増殖に対する神経成長因子(NGF)の抑制効果

    合田光寛, 能木沙織, 網谷慶介, 芳原成美, 北村佳久, 高山房子, 川崎博己

    日本薬理学雑誌   129 ( 2 )   31P   2007.2

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  • マウス腫瘍増殖に対する神経成長因子(NGF)の抑制効果

    合田 光寛, 能木 沙織, 網谷 慶介, 芳原 成美, 北村 佳久, 高山 房子, 川崎 博己

    日本薬理学雑誌   129 ( 2 )   31P - 31P   2007.2

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  • Nerve growth factor(NGF)の血管周囲神経再分布作用におけるアンジオテンシンタイプ2受容体(AT2R)の役割

    吉田 菜三夏, 横溝 綾子, 合田 光寛, 芳原 成美, 高山 房子, 川崎 博己

    日本薬理学雑誌   129 ( 2 )   30P - 30P   2007.2

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  • 加齢に伴うラット腸間膜動脈のメトキサミン収縮に対する内皮依存性抑制の減弱と杜中葉エキス長期投与による改善

    金 きょう, 音無 由紀子, 坪井 崇, 川村 直美, 田川 智恵, 高山 房子, 川崎 博己

    日本薬理学雑誌   129 ( 2 )   22P - 22P   2007.2

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  • 食後高血糖が血圧調節機構に及ぼす影響

    座間味 義人, 高取 真吾, 山脇 康佑, 宮下 智子, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬理学雑誌   129 ( 2 )   32P - 32P   2007.2

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  • 高血圧モデルラットの腸間膜動脈における一酸化窒素含有神経の血管緊張度調節における機能変化

    小山 敏広, 庄司 知世, 畑中 由香子, 合田 光寛, 芳原 成美, 高山 房子, 川崎 博己

    日本薬理学雑誌   129 ( 2 )   32P - 32P   2007.2

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  • 食後高血糖が血圧調節機構に及ぼす影響

    座間味 義人, 高取 真吾, 山脇 康佑, 宮下 智子, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬理学雑誌   129 ( 2 )   32P - 32P   2007.2

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  • ラット腸間膜動脈におけるメトキサミン誘発収縮の内皮依存性抑制及びアセチルコリンによる内皮依存性過分極反応

    金 きょう, 音無 由紀子, 坪井 崇, 川村 直美, 田川 智恵, 高山 房子, 川崎 博己

    血管   30 ( 1 )   27 - 27   2007.1

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  • 2-Kidney,1-Clip(2K-1C)高血圧ラット腸間膜動脈における一酸化窒素(NO)含有神経による血管緊張度調節機能の減弱

    小山 敏広, 庄司 知世, 畑中 由香子, 合田 光寛, 芳原 成美, 高山 房子, 川崎 博己

    血管   30 ( 1 )   28 - 28   2007.1

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  • 脊髄穿刺ラットの神経性血管反応に及ぼす一酸化窒素合成酵素阻害薬の影響

    山脇 康佑, 奥畑 智, 座間味 義人, 高山 房子, 川崎 博己

    血管   30 ( 1 )   28 - 28   2007.1

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  • 食後高血糖を想定した急性高血糖状態における血管反応性の変化

    座間味 義人, 高取 真吾, 山脇 康佑, 宮下 智子, 薮前 奈々, 高山 房子, 見尾 光庸, 川崎 博己

    血管   30 ( 1 )   27 - 27   2007.1

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  • Mechanisms underlying enhanced cGMP-mediated vasodilator responses to various vasodilator agents following endothelium removal in rat mesenteric resistance arteries.

    Yukiko Iwatani, Saori Atagi, Hiromi Numa, Fusako Takayama, Mitsunobu Mio, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103 ( 4 )   84P - 84P   2007

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    DOI: 10.1248/yakushi.127.729

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  • Mechanisms underlying enhanced cGMP-mediated vasodilator responses to various vasodilator agents following endothelium removal in rat mesenteric resistance arteries.

    Yukiko Iwatani, Saori Atagi, Hiromi Numa, Fusako Takayama, Mitsunobu Mio, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103 ( 4 )   84P - 84P   2007

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    DOI: 10.1248/yakushi.127.729

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  • 食後高血糖時の急性高インスリン状態におけるCGRP神経機能減弱とAngiotensin II Type 1受容体の関与

    座間味義人, 高取真吾, 藪前奈々, 宮下智子, 細田美穂, 高山房子, 見尾光庸, 川崎博己

    日本循環薬理学会口演要旨集   17th   42   2007

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  • Long-term administration of Eucommia ulmoides Oliv. leaf extract improves age-related deficiency of endothelium-dependent inhibitory effect on methoxamine-induced excess vasoconstriction in aged rat mesenteric resistance arteries

    Xin Jin, Yukiko Otonashi, Takashi Tsuboi, Naomi Kawamura, Chie Tagawa, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   69P - 69P   2007

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  • Effect of nitric-oxide synthase (NOS) inhibition on blood pressure response to spinal cord stimulation in pithed rats.

    Kosuke Yamawaki, Satoshi Okuhata, Yoshito Zamami, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   145P - 145P   2007

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  • Suppression of tumor growth by nerve growth factor in mice in vivo.

    Mitsuhiro Goda, Saori Atagi, Keisuke Amitani, Narumi Hobara, Yoshihisa Kitamura, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   82P - 82P   2007

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  • Effects of fermented green tea extract on free radical generation in the rat liver mitochondria of an experimental non-alcoholic steatohepatitis model.

    Kazuo Nakamoto, Fusako Takayama, Mitsumasa Mankura, Ying Bai, Kei Morita, Masafumi Ooro, Takao Kaneyuki, Hiromu Kawasaki, Shigeru Okada, Akitane Mori

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   210P - 210P   2007

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  • Perivascular nerves innervate newborn blood vessels in Matrigel in mouse

    Saori Atagi, Mitsuhiro Goda, Keisuke Amitani, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   219P - 219P   2007

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  • The role of angiotensin type 2 receptor (AT2R) on nerve growth factor (NGF) induced-reinnervation of perivascular nerves

    Namika Yoshida, ayako Yokomizo, Mitsuhiro Goda, Mamoru Ouchida, Kenji Simizu, Fusako Takayama, Hiromu Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   219P - 219P   2007

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  • 無麻酔・無拘束ラットのClonidine脳内投与による昇圧反応機序:中枢GABA神経系の関与

    花房伸幸, 岡本和明, 北村佳久, 高山房子, 川崎博己

    日本循環薬理学会口演要旨集   17th   82   2007

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  • Evaluation of Newly Developed Educational System for Pharmacy Students through Preliminary Training Trial on Dispensing Practice

    NISHIHARA SHIGEKI, OKAZAKI HIROMI, KAWAKAMI YASUHIRO, YOSHITOMI HIRONORI, KAWASAKI HIROMU, KUROSAKI YUJI, TAKAYAMA FUSAKO, KITAMURA YOSHIHISA, SENDO TOSHIAKI, SHIBATA KAZUHIKO, GOMITA YUTAKA

    医療薬学   32 ( 10 )   1044 - 1049   2006.10

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    At Okayama University, a pharmacy educational curriculum requiring a period of six-years was started in April, 2006 and in its novel core curriculum, long-term practical training in a hospital is specified. Preliminary practical training based on the core curriculum was conducted to uncover problems in the long-term hospital training. The preliminary training, which was given to fourth-year undergraduate students and focused on dispensing practice, was preceded by lectures. Arrangements for the training included the preparation of a new textbook, drawing up evaluation criteria, the appointm...

    DOI: 10.5649/jjphcs.32.1044

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  • 30P2-141 生体肝移植患者におけるタクロリムスのTDMの指標に関する検討(薬物動態(TDM・投与設計等),医療薬学の扉は開かれた)

    合田 光寛, 河崎 陽一, 川上 英治, 北村 佳久, 千堂 年昭, 高山 房子, 八木 孝仁, 田中 紀章, 五味田 裕, 川崎 博己

    日本医療薬学会年会講演要旨集   16   2006.9

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  • 神経成長因子(NGF)のin vivoにおける腫瘍増殖抑制効果に関する検討

    合田光寛, 能木沙織, 網谷慶介, 北村佳久, 高山房子, 川崎博己

    生体機能と創薬シンポジウム   2006   147 - 148   2006.9

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  • 01P1-110 小児科病棟における看護師への注射薬取り扱いに関する情報提供への取り組み(医薬品適正使用,医療薬学の扉は開かれた)

    山脇 康佑, 川島 理恵子, 西原 茂樹, 千堂 年昭, 高山 房子, 矢野 香苗, 五味田 裕, 川崎 博己

    日本医療薬学会年会講演要旨集   16   2006.9

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  • 食後高血糖が神経性血圧調節機能に及ぼす影響

    座間味義人, 高取真吾, 山脇康佑, 宮下智子, 高山房子, 見尾光庸, 川崎博己

    生体機能と創薬シンポジウム   2006   144 - 146   2006.9

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  • 30-G-06 光に不安定な薬剤の簡易懸濁法を用いた投与方法について(医薬品適正使用,医療薬学の扉は開かれた)

    座間味 義人, 槙田 崇志, 安藤 哲信, 倉田 なおみ, 合葉 哲也, 黒崎 勇二, 天野 学, 名和 秀起, 北村 佳久, 千堂 年昭, 五味田 裕, 高山 房子, 川崎 博己

    日本医療薬学会年会講演要旨集   16   2006.9

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  • 01P2-013 造血幹細胞移植患者における抗真菌薬の使用状況(薬物療法(基礎と臨床),医療薬学の扉は開かれた)

    能木 沙織, 北川 航平, 北村 佳久, 千堂 年昭, 高山 房子, 五味田 裕, 川崎 博己

    日本医療薬学会年会講演要旨集   16   2006.9

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  • 急性高血糖が神経性血圧調節機能に及ぼす影響

    座間味 義人, 高取 真吾, 山脇 康佑, 宮下 智子, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬理学雑誌   128 ( 2 )   17P - 17P   2006.8

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  • ラット腸間膜動脈血管における膜型グアニル酸シクラーゼを介する血管弛緩反応の内皮細胞除去による増強機序

    岩谷 有希子, 沼 裕美, 能木 沙織, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬理学雑誌   128 ( 2 )   17P - 17P   2006.8

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  • 急性高血糖が神経性血圧調節機能に及ぼす影響

    座間味 義人, 高取 真吾, 山脇 康佑, 宮下 智子, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬理学雑誌   128 ( 2 )   17P - 17P   2006.8

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  • 簡易懸濁法を用いた経管栄養チューブによる薬剤投与方法の改善

    座間味 義人, 高山 房子, 川崎 博己, 石井 雅人, 柴田 和彦, 五味田 裕

    TDM研究   23 ( 2 )   101 - 102   2006.4

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  • 卵黄タンパク質分解物のヒトに対する血圧降下作用

    金田 輝之, 羽田 尚彦, 野村 政孝, 青野 祥子, 高山 房子, 栗木 隆吉, 戸部 和夫, 川崎 博己

    日本栄養・食糧学会大会講演要旨集   60回   99 - 99   2006.4

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  • ラット腸間膜動脈血管弛緩反応の内皮細胞除去による増強機序

    岩谷 有希子, 能木 沙織, 高山 房子, 見尾 光庸, 川崎 博己

    日本平滑筋学会雑誌   10 ( 1 )   J - 27   2006.4

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  • 肝移植施行後の胆汁うっ滞によるシクロスポリンの血中濃度低下が認められた一例

    中本 賀寿夫, 高山 房子, 川崎 博己, 河崎 陽一, 柴田 和彦, 五味田 裕

    TDM研究   23 ( 2 )   139 - 140   2006.4

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  • 生体肝移植患者におけるタクロリムス体内動態と臨床検査値に関する検討

    合田哲也, 河崎陽一, 川上英二, 北村佳久, 高山房子, 川崎博己, 柴田和彦, 八木孝仁, 田中紀章, 五味田裕

    日本薬学会年会要旨集   126th ( 2 )   183   2006.3

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  • 薬学における創薬を目指した個体薬理学の新展開 ラット腸間膜動脈血管床の内皮細胞除去による血管弛緩反応増強機序

    岩谷 有希子, 沼 裕美, 能木 沙織, 高山 房子, 見尾 光庸, 川崎 博己

    日本薬学会年会要旨集   126年会 ( 1 )   253 - 253   2006.3

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  • 生体肝移植患者におけるタクロリムス体内動態と臨床検査値に関する検討

    合田 哲也, 河崎 陽一, 川上 英二, 北村 佳久, 高山 房子, 川崎 博己, 柴田 和彦, 八木 孝仁, 田中 紀章, 五味田 裕

    日本薬学会年会要旨集   126年会 ( 2 )   183 - 183   2006.3

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  • ワルファリンを用いた抗凝固療法中の血液凝固能における季節変化の影響

    小山 敏広, 森 英樹, 高山 房子, 川崎 博己, 柴田 和彦, 五味田 裕, 出石 文男

    日本薬学会年会要旨集   126年会 ( 2 )   192 - 192   2006.3

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  • フルクトース負荷ラットのインスリン抵抗性に及ぼすローヤルゼリー長期投与の影響

    座間味 義人, 高取 真吾, 野村 政孝, 中妻 章, 見尾 光庸, 高山 房子, 川崎 博己

    日本薬学会年会要旨集   126年会 ( 3 )   136 - 136   2006.3

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  • Neuronal nitric-oxide synthase inhibition facilitates adrenergic neurotransmission in rat mesenteric resistance arteries International journal

    Y Hatanaka, N Hobara, J Honghua, S Akiyama, H Nawa, Y Kobayashi, F Takayama, Y Gomita, H Kawasaki

    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS   316 ( 2 )   490 - 497   2006.2

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    The effects of nonselective nitric-oxide synthase ( NOS) inhibitors [N-omega-nitro-L-arginine methyl ester (L-NAME) and N-omega-nitro-L-arginine (L-NNA)] and specific neuronal NOS ( nNOS) inhibitor [vinyl-L-N-5-(1-imino-3-butenyl)-L-ornithine (L-VNIO)] on adrenergic nerve-mediated vasoconstriction were studied in rat perfused mesenteric vascular beds without endothelium. Perfusion of L-NAME, L-NNA, or L-VNIO markedly augmented vasoconstrictor responses to periarterial nerve stimulation (PNS; 2-8 Hz) without affecting vasoconstriction induced by exogenously injected norepinephrine (NE). Addition of L-arginine, a precursor for the synthesis of nitric oxide (NO), reversed the augmentation of the PNS response by L-NAME. The PNS (8 Hz)-evoked NE release in the perfusate was increased by L-NAME perfusion. In preparations treated with capsaicin [a depleter of calcitonin gene-related peptide (CGRP)-containing nerves], L-NAME did not augment vasoconstrictor responses to PNS or NE injection. Combined perfusion of CGRP(8-37) (a CGRP receptor antagonist) and L-NAME induced additive augmentation of the vasoconstrictor response to PNS but did not affect the response to NE injection. In preparations with active tone produced by methoxamine and in the presence of guanethidine, L-NAME perfusion did not affect the vasodilator response induced by PNS. Immunostaining of the mesenteric artery showed the presence of nNOS-like immunopositive nerve fibers, which were absent in arteries pretreated with capsaicin. These findings suggest that NO, which is released from perivascular capsaicin-sensitive nerves, presynaptically inhibits neurogenic NE release to modulate adrenergic neurotransmission.

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  • Histamine-induced vasodilation and vasoconstriction in the mesenteric resistance artery of the rat International journal

    H Jin, T Koyama, Y Hatanaka, S Akiyama, F Takayama, H Kawasaki

    EUROPEAN JOURNAL OF PHARMACOLOGY   529 ( 1-3 )   136 - 144   2006.1

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    The present study was designed to examine the vascular response to histamine in rat perfused mesenteric vascular beds with active tone. In preparations with intact endothelium, perfusion of histamine (1 nM-100 mu M) produced a concentration-dependent vasodilation. Histamine-induced vasodilation was attenuated by L-NAME (nitric oxide (NO) synthase inhibitor, 100 mu M) and olopatadine (histamine H, receptor antagonist, 1 mu M) but not by laftitidine (histamine H-2 receptor antagonist, 1 mu M). Cold-storage denervation (4 degrees C for 72 h) of the preparation with intact endothelium attenuated the histamine-induced vasodilation. In preparations without endothelium, histamine at low concentrations (1-100 nM) produced only a small and rapid vasodilation, whereas histamine at concentrations higher than 1 mu M produced triphasic vascular responses: initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. Lafutidine abolished only the histamine-induced initial vasodilation. Olopatadine abolished the histamine-induced second vasoconstriction and third vasodilation. Cold-storage denervation of the denuded preparation abolished the histamine-induced second vasoconstriction and third vasodilation. These findings suggest that histamine induced endothelium-dependent vasodilation via endothelium histamine H-1 receptors and endothelium-independent vasodilation via smooth muscle histamine H-2 receptors. It is also suggested that the histamine-induced endothelium-independent vasoconstriction and vasodilation are mediated by histamine H-1 receptors and perivascular nerves. (c) 2005 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ejphar.2005.10.060

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  • Histamine-induced vasodilation and vasoconstriction in the mesenteric resistance artery of the rat

    H Jin, T Koyama, Y Hatanaka, S Akiyama, F Takayama, H Kawasaki

    EUROPEAN JOURNAL OF PHARMACOLOGY   529 ( 1-3 )   136 - 144   2006.1

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    The present study was designed to examine the vascular response to histamine in rat perfused mesenteric vascular beds with active tone. In preparations with intact endothelium, perfusion of histamine (1 nM-100 mu M) produced a concentration-dependent vasodilation. Histamine-induced vasodilation was attenuated by L-NAME (nitric oxide (NO) synthase inhibitor, 100 mu M) and olopatadine (histamine H, receptor antagonist, 1 mu M) but not by laftitidine (histamine H-2 receptor antagonist, 1 mu M). Cold-storage denervation (4 degrees C for 72 h) of the preparation with intact endothelium attenuated the histamine-induced vasodilation. In preparations without endothelium, histamine at low concentrations (1-100 nM) produced only a small and rapid vasodilation, whereas histamine at concentrations higher than 1 mu M produced triphasic vascular responses: initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. Lafutidine abolished only the histamine-induced initial vasodilation. Olopatadine abolished the histamine-induced second vasoconstriction and third vasodilation. Cold-storage denervation of the denuded preparation abolished the histamine-induced second vasoconstriction and third vasodilation. These findings suggest that histamine induced endothelium-dependent vasodilation via endothelium histamine H-1 receptors and endothelium-independent vasodilation via smooth muscle histamine H-2 receptors. It is also suggested that the histamine-induced endothelium-independent vasoconstriction and vasodilation are mediated by histamine H-1 receptors and perivascular nerves. (c) 2005 Elsevier B.V. All rights reserved.

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  • 自由行動下ラットにおけるNO合成酵素阻害薬L-NAME静脈内投与による昇圧反応機序

    根木 真一, 花房 伸幸, 高山 房子, 川崎 博己

    日本薬理学雑誌   127 ( 1 )   31P - 31P   2006.1

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  • SOD様活性を示すtempolのラット腸間膜動脈抵抗血管における血管反応

    中本 賀寿夫, 武田 章利, 高山 房子, 川崎 博己

    日本薬理学雑誌   127 ( 1 )   33P - 33P   2006.1

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  • Innervation and functional changes in mesenteric perivascular calcitonin gene-related peptide- and neuropeptide Y-containing nerves following topical phenol treatment

    N. Hobara, M. Goda, Y. Kitamura, F. Takayama, H. Kawasaki

    NEUROSCIENCE   141 ( 2 )   1087 - 1099   2006

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    We have previously shown that age-related reduction of innervation and function in mesenteric perivascular calcitonin gene-related peptide-containing vasodilator nerves takes place in spontaneously hypertensive rats. The present study was performed to investigate innervation and functional changes in perivascular calcitonin gene-related peptide-and adrenergic neuropeptide Y-containing nerves after topical treatment with phenol, which damages nerve fibers, around the rat superior mesenteric artery. Under pentobarbital-Na anesthesia, 8-week-old Wistar rats underwent in vivo topical application of phenol (10% phenol in 90% ethanol) or saline (sham rats) to the superior mesenteric artery proximal to the bifurcation of the abdominal aorta. After the treatment, the animals were subjected to immunohistochemistry of the 3rd branch of small arteries proximal to the intestine and to vascular responsiveness testing on day 3 through day 14. The innervation levels of calcitonin gene-related peptide-like immunoreactivity containing fibers and neuropeptide Y-like immunoreactivity containing fibers were markedly reduced on day 3 to day 14 and on day 5 to day 14 after the treatment, compared with those in sham-operated rats, respectively. In perfused mesenteric vascular beds isolated from phenol-treated rats, adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide nerve-mediated vasodilation in response to periarterial nerve stimulation (2-12 Hz) were significantly decreased on day 3 and day 7. Neurogenic release of norepinephrine in phenol-treated rats on day 7 was significantly smaller that that in sham-operated rats. Nerve growth factor content in the mesenteric arteries of phenol-treated rats was significantly lower than that in sham-operated rats. Administration of nerve growth factor using osmotic mini-pumps for 7 days after the phenol treatment resulted in greater density of calcitonin gene-related peptide-and neuropeptide Y-like immunoreactivity fibers than in phenol-treated rats and restored decreased vascular responses to periarterial nerve stimulation. These results suggest that topical phenol-treatment of the mesenteric artery effectively induces functional denervation of perivascular nerves, which can be prevented or reversed by nerve growth factor treatment. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.

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  • 30P1-075 泌尿器科におけるがん化学療法支援のための看護師向けマニュアルの作成とその評価(癌薬物療法(外来化学療法、緩和ケア等),医療薬学の扉は開かれた)

    大呂 真史, 五味田 裕, 川崎 博己, 名和 秀起, 毎熊 真理, 庵谷 亜希子, 相良 英憲, 千堂 年昭, 高山 房子, 雑賀 隆史, 日野 洋子

    日本医療薬学会年会講演要旨集   16 ( 0 )   2006

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  • Facilitatory effect of hepatocyte growth factor (HGF) on redistribution of perivascular nerves in the rat mesenteric artery

    N Hobara, M Goda, F Takayama, H Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   100   87P - 87P   2006

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  • Effect of adrenomedullin on adrenergic vasoconstriction in mesenteric resistance arteries of the rat

    S Akiyama, Y Hatanaka, N Hobara, J Honghua, K Kosugi, F Takayama, H Kawasaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   99 ( 3 )   264 - 271   2005.11

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    Adrenomedullin (AM) is a hypotensive peptide that belongs to a family of peptides structurally related to calcitonin gene-related peptide (CGRP). The present study examined the effect of AM on adrenergic nerve-mediated vasoconstriction in rat perfused mesenteric vascular beds without endothelium. Perfusion of AM at 0.1 nM but not 10 nM increased vasoconstrictor responses to periarterial nerve stimulation (PNS) (1 - 4 Hz), while AM at 10 nM significantly attenuated vasoconstriction induced by bolus injection of norepinephrine (NE). In preparations treated with capsaicin (a CGRP depletor), pressor responses to both PNS and NE injection were markedly attenuated by AM. Perfusion of CGRP(8 - 37) (a CGRP-receptor antagonist) significantly potentiated the PNS- but not the NE-induced vasoconstriction. Combined perfusion of CGRP(8 - 37) and AM had no effect on the PNS-induced response and antagonized the inhibitory effect of AM on the NE-induced response. AM(22 - 52) (an AM-receptor antagonist) did not influence the effect of AM. These findings suggest that AM facilitates adrenergic vasoconstriction by inhibiting neurotransmission of CGRP-containing nerves, which counteract adrenergic nerve-mediated vasoconstriction.

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  • 抵抗血管収縮に対する内皮由来弛緩因子(NOおよびEDHF)の抑制的調節と加齢変化

    音無 由紀子, 内堀 聡子, 川村 直美, 坪井 崇, 高山 房子, 川崎 博己

    日本薬理学雑誌   126 ( 4 )   14P - 14P   2005.10

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  • 卵黄蛋白由来ペプチドの降圧作用

    野村 政孝, 青野 祥子, 根木 真一, 金田 輝之, 羽田 尚彦, 高山 房子, 川崎 博己

    日本薬理学雑誌   126 ( 4 )   14P - 14P   2005.10

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  • P-208 肝移植後の免疫抑制薬の血中濃度及び臨床検査値の変動推移と酸化ストレス障害に関する検討(9.薬物動態(TDM・投与設計等)1,医療薬学の未来へ翔(はばた)く-薬剤師の薬剤業務・教育・研究への能動的関わり-)

    中本 賀寿夫, 河崎 陽一, 北村 佳久, 高山 房子, 川崎 博己, 三宅 悟, 柴田 和彦, 八木 孝仁, 田中 紀章, 五味田 裕

    日本医療薬学会年会講演要旨集   15   2005.9

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  • P-262 簡易懸濁法を用いたワルファリンの投与量設定について(12.調剤・処方管理、オーダリング(注射剤含む)2,医療薬学の未来へ翔(はばた)く-薬剤師の薬剤業務・教育・研究への能動的関わり-)

    座間味 義人, 天野 学, 岡崎 宏美, 田川 真大, 石井 雅人, 黒崎 勇二, 高山 房子, 川崎 博巳, 柴田 和彦, 五味田 裕

    日本医療薬学会年会講演要旨集   15   2005.9

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  • Long-term inhibition of angiotensin prevents reduction of periarterial innervation of calcitonin gene-related peptide (CGRP)-containing nerves in spontaneously hypertensive rats International journal

    N Hobara, N Gessei-Tsutsumi, M Goda, F Takayama, S Akiyama, Y Kurosaki, H Kawasaki

    HYPERTENSION RESEARCH   28 ( 5 )   465 - 474   2005.5

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    The aim of this study was to investigate age-related changes in the density of calcitonin gene-related peptide (CGRP)-containing nerve fibers in spontaneously hypertensive rats (SHR) and the effects of long-term inhibition of the renin-angiotensin system on these changes. The density of immunocytochemically stained nerve fibers in the mesenteric artery was quantified by computer-assisted image processing. An age-related decrease in the density of CGRP-like immunoreactive (Li)-containing nerve fivers but not neuropeptide Y (NPY)-LI-containing sympathetic nerve fibers was found in the mesenteric artery of SHR but not Wistar Kyoto rats (WKY). The density of NPY-LI-containing sympathetic nerve fibers was significantly greater in SHR than in WKY. SHR were treated for 7 weeks with angiotensin converting enzyme inhibitor (0.005% temocapril), angiotensin 11 type-1 (AT,) receptor antagonist (0.025% Iosartan) or vasodilator (0.01% hydralazine) in their drinking water. Each drug treatment significantly lowered the systolic blood pressure measured by tail-cuff method. Long-term treatment of SHR with temocapril and Iosartan significantly increased the density of CGRP-LI-containing nerve fibers in mesenteric arteries. However, the density after hydralazine treatment was similar to the level in non-treated SHR. The density of NPY-LI-containing nerve fibers was not increased by any of the drug treatments. These results suggest that long-term inhibition of the renin-angiotensin system in SHR prevents remodeling of CGRPergic nerve fibers and prevents the reduction of CGRPergic nerve function.

    DOI: 10.1291/hypres.28.465

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  • インスリン抵抗性病態に及ぼすRoyal Jelly長期投与の影響

    野村 政孝, 圓尾 奈緒美, 中妻 章, 高山 房子, 川崎 博己

    日本薬学会年会要旨集   125年会 ( 3 )   133 - 133   2005.3

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  • 高血圧における血管周囲神経リモデリングとレニン-アンジオテンシン系阻害薬長期投与による改善効果

    芳原 成美, 合田 光寛, 高山 房子, 川崎 博己

    日本薬理学雑誌   124 ( 補冊1 )   85P - 86P   2004.11

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    抵抗血管には外膜周囲を網目状にとりまく血管周囲神経が分布し血管緊張度調節に大きな役割を担っている.主な血管周囲神経として血管収縮性の交感神経と血管拡張性のカルシトニン遺伝子関連ペプチド(CGRP)含有神経が知られている.両神経は相反的な支配によって血管の緊張度調節を行っている.高血圧自然発症ラット(SHR)ではCGRP神経のみがその分布と機能が加齢とともに減弱し,血管周囲神経リモデリングが見られる.その結果,神経リモデリングを起こさない交感神経機能が亢進して血圧上昇が生じている可能性が示唆されている.SHRにレニン-アンジオテンシン系阻害薬を長期間投与することによって,腸間膜動脈抵抗血管におけるGGRP神経の機能と神経分布密度の増加が確認された.この結果は長期のレニン-アンジオテンシン系阻害が血管周囲神経の機能と分布密度を変化させることで,血管周囲神経リモデリングの改善につながったものと考えられる(著者抄録)

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  • P-39 経管栄養チューブによる薬剤投与方法の改善について : 簡易懸濁法(2.医薬品適正使用,"薬剤師がつくる薬物治療"-薬・薬・学の連携-)

    座間味 義人, 石井 雅人, 高山 房子, 柴田 和彦, 川崎 博己, 五味田 裕

    日本医療薬学会年会講演要旨集   14   2004.9

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  • Zinc benzoate, a contaminating environmental compound derived from polystyrene resin inhibits A-type monoamine oxidase International journal

    T Egashira, K Sakai, F Takayama, M Sakurai, S Yoshida

    TOXICOLOGY LETTERS   145 ( 2 )   161 - 165   2003.11

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    The contaminants in deionized and distilled water (DDI water) boiled with polystyrene resin inhibited A-type monoamine oxidase (MAO. MAO-A preferentially deaminates serotonin and norepinephrine and regulates these amines concentration) activity in monkey brain mitochondria. To identify these contaminants, we attempted measurements by HPLC, FT-IR and NMR. The compound inhibiting MAO-A activity was zinc benzoate. Although it potently inhibited MAO-A activity, zinc benzoate did not effect MAO-B in monkey brain mitochondria. It also reversibly and competitively inhibited MAO-A activity in a dose-dependent manner. Zinc benzoate, however, did not inhibit either MAO-A or -B activities in rat brain mitochondria. These results indicate that zinc benzoate, which inhibits MAO-A activity, is easily incorporated in DDI water by boiling polystyrene and also may be a contaminating environmental chemical compound that alters the levels of serotonin and norepinephrine in the central nervous system. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

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  • Calcium disodium edetate enhances type A monoamine oxidase activity in monkey brain International journal

    T Egashira, K Sakai, M Sakurai, F Takayama

    BIOLOGICAL TRACE ELEMENT RESEARCH   94 ( 3 )   203 - 211   2003.9

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    The effects of metal chelators on monoamine oxidase (MAO) isozymes, MAO-A and MAO-B, in monkey brain mitochondria were investigated in vitro. MAO-A activity increased to about 40% with 0.1 muM calcium disodium edetate (CaNa(2)EDTA) using serotonin as a substrate, and this activation was proportional to the concentration of CaNa(2)EDTA. On the other hand, MAO-A activities were decreased gradually with an increasing concentration of o-phenanthroline and diethyldithiocarbamic acid, but these metal chelators had no effect on MAO-B activity in monkey brain. The activation of MAO-A activity by CaNa(2)EDTA was reversible. CaNa(2)EDTA did not activate both MAO-A and MAO-B activities in rat brain mitochondria. Zn and Fe ions were found in the mitochondria of monkey brain. Zn ions potently inhibited MAO-A activity, but Fe ions did not inhibit either MAO-A or MAO-B activity in monkey brain mitochondria. These results indicate that the activating action of CaNa(2)EDTA on MAO-A was the result of the chelating of Zn ions contained in mitochondria by CaNa(2)EDTA. These results also indicate the possibility that Zn ions may regulate physiologically the level of serotonin and norepinephrine content in brain by inhibiting a MAO-A activity.

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  • Changes of materials that scavenge 1,1-diphenyl-2-picrylhydrazyl radicals in plasma by per-oral administration of Kampo medicine, Ninjin-yoei-to in rats International journal

    T Egashira, F Takayama, Y Komatsu

    JOURNAL OF PHARMACY AND PHARMACOLOGY   55 ( 3 )   367 - 371   2003.3

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    The Kampo medicine, Ninjin-yoei-to, scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals in a dose-dependent fashion as did ascorbic acid and a-tocopherol. Ninjin-yoei-to, which is composed of 12 herbs, had a potent DPPH radical scavenging ability. We investigated the transition of the materials that scavenge DPPH radicals in plasma after oral administration of Ninjin-yoei-to to rats. When 1.0 g kg(-1) Ninjin-yoei-to was administered, the DPPH radical scavenging ability increased at 30 min and biphasic peaks were observed at 2 h and at 10 h. From the response-time profile, kinetic parameters including values for K-a (absorption rate constant), t(max) (peak concentration time), t(1/2) (half-life) and MRT (mean residence time) of the radical scavenging ability in plasma could be calculated for DPPH radicals. K-a values were 0.53 +/- 0.03 and 0.36 +/- 0.07 h, t(max) values were 2.1 +/- 1.04 and 8.56 +/- 2.69 h, t(1/2) values were 1.60 +/- 0.12 and 3.39 +/- 1.72 h, and MRT values were 4.14 +/- 1.59 and 8.18 +/- 2.55 h, respectively. These parameters calculated from the antioxidation dynamics were considered to offer a very meaningful procedure for examining the effects of Ninjin-yoei-to.

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  • Inhibition by Zn(2+) of A-form monoamine oxidase in monkey brain mitochondria

    T Egashira, F Takayama, K Sakai

    JOURNAL OF PHARMACOLOGICAL SCIENCES   91 ( 3 )   239 - 245   2003.3

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    The effects of ZnSO(4) on mitochondrial monoamine oxidase (MAO) activity in monkey brain were compared with those in rat and rabbit, in vitro. After preincubation at 25degreesC for 20 min with 1 muM ZnSO(4), MAO-A activity in monkey brain was about 50% using serotonin (5-HT) as a substrate, and the inhibition was proportional to the concentration of ZnSO(4). However, ZnSO(4) had no effect on MAO-B activity in monkey brain using 8-phenylethylamine (beta-PEA) as a substrate. The inhibition by ZnSO(4) of MAO-A activity was competitive and reversible. CdSO(4) also inhibits MAO-A, but not MAO-B in monkey brain mitochondria. ZnSO(4) did not inhibit either MAO-A or MAO-B activity in rat and rabbit brain mitochondria. These results indicate that the inhibiting action of Zn(2+) differs depending on animal species. In monkey brain mitochondria, MAO-A was highly sensitive to Zn(2+) and MAO-B was less sensitive. These results also suggest that Zn(2+) may regulate the level of catecholamine content in monkey brain.

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  • Effects of zinc ion on type A monoamine oxidase in monkey brain mitochondria International journal

    T Egashira, F Takayama, K Sakai

    BIOCHEMICAL PHARMACOLOGY   65 ( 4 )   625 - 627   2003.2

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    The effects of ZnSO4 on types A and B monoamine oxidase (MAO) isozymes in monkey brain mitochondria were investigated, in vitro. Type A MAO activity in monkey brain decreased to about 50% with 1 muM ZnSO4 using serotonin as a substrate, and this inhibition was proportional to the concentration of ZnSO4, ZnSO4 had no effect, however, on type B MAO activity in monkey brain using Pphenylethylamine as a substrate. The inhibition by ZnSO4 of type A MAO activity was competitive and reversible. ZnSO4 did not inhibit either type A or type B MAO activity in rat brain mitochondria. Almost similar results were also obtained when ZnCl2 was used, ill vitro. These results indicate that the inhibiting action of zinc ion differs depending on animal species and organ. Type A MAO in monkey brain mitochondria was highly sensitive to zinc ion. while type B activity was less sensitive. (C) 2002 Elsevier Science Inc. All rights reserved.

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  • Pharmacokinetics of Glycyrrhizin and Glycyrrhetic Acid Followin Glycyrrhizin Administration to Rats with Single and Multiple Doses via Different Routes

    Egashira Toru, Takayama Fusako, Yufu Fumie, Shoyama Yukihiro

    Japanese Pharmacology & Therapeutics   2003

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  • 水浸拘束ストレス負荷ラットにおける血中の酸化的ストレス状態に関する検討

    高山 房子, 江頭 亨, 山中 康光

    日本薬理学雑誌   119 ( 3 )   66P - 66P   2002.3

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  • Change in free radical-related substances in plasma following ischemia-reperfusion in rat liver International journal

    Atsuko Iwamoto, Toru Egashira, Fusako Takayama, Yasumitsu Yamanaka, Takayuki Noguchi

    Pathophysiology   8 ( 3 )   167 - 174   2002

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    In order to clarify the relationship between free radicals and liver injury due to ischemia-reperfusion, we investigated the dynamics of radical-related substances in the blood of rats after liver ischemia-reperfusion. Subsequent to 60 min of liver ischemia, the generation of reactive oxygen species (ROS) from polymorphonuclear leukocytes (PMNs) initiated by phorbol myristate acetate (PMA) and lipid peroxidation significantly increased 2 h after reperfusion and showed peak values at 8-10 h. These values returned to the control level 32 h after reperfusion. The levels of nitric oxide metabolites (NOx, NO2-+NO3-) increased biphasically at 10 and 32 h during the period of reperfusion, but did not return to control levels. Cu,Zn-superoxide dismutase (SOD) levels increased immediately after 5 min of reperfusion and showed a peak value after 20 min. This increase diminished gradually and returned to the control level 10 h after reperfusion. Mn-SOD increased 2 h after reperfusion, and this level was maintained for 48 h. The levels did not show increases at the end of ischemia and were nearly identical to the pre-ischemia levels. These finding obtained from the dynamics of radical-related substances are considered very meaningful for investigating mechanisms in the pathogenesis of liver injury by ischemia-reperfusion, and are clinically important in liver transplantation. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

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  • Free radicals and oxidative stress: Targeted ESR measurement of free radicals

    Toru Egashira, Fusako Takayama

    Folia Pharmacologica Japonica   120 ( 4 )   229 - 236   2002

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    The detection of free radicals generated within the body may contribute to clarifying the pathophysiological role of free radicals in disease processes. As an appropriate procedure to examine the generation of free radicals in a biological system, electron spin resonance (ESR) has emerged as a powerful tool for detection and identification. A method for determination of oxygen radical scavenging activity using ESR and the spin trapping technique was developed. Oxygen radicals were trapped by 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) or α-phenyl-N-t-butylnitrone (PBN), and the DMPO or PBN spin aduct signal was measured quantitatively by an ESR spectrometer. The spin trapping method using ESR has also been reported for not only in vitro and ex vivo measurements but also in vivo measurements. In in vivo ESR, nitroxyl radical is being used as a spin trap well. ESR signal intensities of nitroxyl radical are measured after administration to animals and the signal decay rates of nitroxyl radical have reported to be influenced by various types of oxidative stress. With this method, it is possible to specify the type of radical or the location at which the free radicals are produced. The spin trapping method by in vivo ESR is an effective procedure for giving non-invasive measurements in animals. ESR imaging in the organs of live animals can also be obtained after injection of nitroxyl radicals as an imaging agent using ESR-computed tomography. In vivo ESR imaging has been established as a powerful technique for determining the spatial distribution of free radicals in living organs and tissues.

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  • Effect of endotoxin-induced reactive oxygen species on sperm motility

    K Urata, H Narahara, Y Tanaka, T Egashira, F Takayama, Miyakawa, I

    FERTILITY AND STERILITY   76 ( 1 )   163 - 166   2001.7

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    Objective: To define the mechanism of infection-induced damage of sperm.
    Design: The effect of lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) on sperm motility and its modification by scavengers were investigated.
    Setting: Research laboratory of a university hospital.
    Patient(s): Normozoospermic semen samples were obtained from 37 healthy volunteers.
    Intervention(s): The sperms were incubated in the presence of LPS with or without scavengers.
    Main Outcome Measure(s): Sperm motility was evaluated by a sperm quality analyzer (SQAIIB). ROS formation in semen samples was measured by a Berthold luminometer (LB953).
    Result(s): Motility of spermatozoa was decreased in the LPS-treated samples compared with that in the control groups. ROS was significantly higher in the LPS-treated groups than in the control groups. The addition of ROS scavengers restored the motility index and suppressed ROS production in the LPS-treated semen samples.
    Conclusion(s): These data suggest that endotoxin-induced excessive production of ROS is responsible for the decrease in sperm motility and that antioxidant therapy may be a therapeutic option for infertile men with bacterial genital tract infection. (C) 2001 by American Society for Reproductive Medicine.

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  • Singlet oxygen generation from phosphatidylcholine hydroperoxide in the presence of copper

    F Takayama, T Egashira, Y Yamanaka

    LIFE SCIENCES   68 ( 15 )   1807 - 1815   2001.3

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    This study pursued whether singlet oxygen (O-1(2)) is generated from phosphatidylcholine hydroperoxide (PCOOH), the oxidized modification product of a major constituent of biomembranes and serum lipoproteins. The O-1(2) formation was detected, by utilizing the oxidation of 2,2,6,6-tetramethyl- 4-piperidone (TMPD) by O-1(2) to yield 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (TEMPONE), which generates electron spin resonance (ESR) signals. The TEMPONE signal was detected in human plasma with addition of PCOOH by ESR determination after introducing copper(II). The TEMPONE formation was proportional to the amounts of PCOOH added according to moles of active oxygen. The TEMPONE signal intensity was weakened significantly in the presence of beta -carotene and histidine in a concentration-dependent manner, but was not at all decreased by mannitol, Mn-superoxide dismutase and catalase. In addition, HPLC-chemiluminescence analysis demonstrated that incubation with the PCOOH/Cu(II) combination oxidized cholesterol, a relatively oxidation-resistant component, to the cholesterol hydroperoxide. These results reveal that O-1(2) is generated from PCOOH in contact with copper(II). In conclusion, this in-vitro study provides directly the O-1(2) formation in living organisms following the advancement of peroxidation of constitutive lipids. (C) 2001 Elsevier Science Inc. All rights reserved.

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  • Protective effect of Ninjin-yoei-to on damage to isolated hepatocytes following transient exposure to tert-butyl hydroperoxide

    F Takayama, T Egashira, Y Yamanaka

    JAPANESE JOURNAL OF PHARMACOLOGY   85 ( 3 )   227 - 233   2001.3

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    To establish a simple screening system for estimating efficacy of an agent for an oxidative-related lesion, we investigated the damage in isolated rat hepatocytes exposed to 75 muM tert-butyl hydroperoxide (t-BuOOH) and then subsequently incubated the cells in fresh medium. By electron spin resonance spectroscopy analysis using 5,5-dimethyl-1-pynoline-N-oxide (DMPO), DMPO adducts of tert-butoxyl radicals and carbon center radicals were detected during the t-BuOOH exposure, and DMPO-OH formation was detected after t-BuOOH removal. In t-BuOOH-exposed cells, the level of phosphatidylcholine hydroperoxide (PCOOH), a peroxidative product of biomembranes in the hepatocytes, and the leakage of enzymes into the culture medium were significantly increased. An increase in acid phosphatase (AP) activity representing lysosome destabilization preceded the aspartate oxoglutarate aminotransferase (AST), alanine oxoglutarate aminotransferase (ALT) and lactate dehydrogenase (LDH) leakage. Ninjin-yoei-to added to the culture medium following the t-BuOOH exposure significantly inhibited the PCOOH formation and the leakage of AP, AST, ALT and LDH, concentration- dependently. Ninjin-yoei-to at 1 mg/ml in culture medium completely diminished these increases in enzyme activities down to the background levels found in control experiments and this reduction was greater than the most effective alpha -tocopherol concentration of 20 mu mol /ml. Considering all of these results, it is likely Ninjin-yoei-to, may exert its protective effect by antioxidative action and membrane stabilization.

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  • フリーラジカルに関する基礎事項。フリーラジカルの測定法.

    江頭 亨, 高山房子, 山中康光

    Clinical Neuroscience   19; 516-519,   2001

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  • Styrene inhibits monoamine oxidase A, but not monoamine oxidase B in monkey brain mitochondria

    Toru Egashira, Fusako Takayama, Kumiko Sakai, Yasumitsu Yamanaka

    Toxicology Letters   117 ( 1-2 )   115 - 119   2000.9

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    The effects of styrene on mitochondrial monoamine oxidase (MAO) activity in rat and monkey brains were compared in vitro. After preincubation at 25°C for 20 min with 1 mM styrene monomer MAO-A activity in monkey brain was inhibited potently using 5-HT (for MAO-A substrate), but MAO-B activity in monkey brain and platelets were slightly inhibited using β-PEA (for MAO-B substrate). Styrene monomer also competitively inhibited MAO-A activity in a dose-dependent manner. MAO-A in monkey brain was inhibited by styrene in ascending order of potency: styrene trimer&gt
    styrene dimer&gt
    styrene monomer. In contrast styrene monomer slightly inhibited both MAO-A and MAO-B activities in rat brain mitochondria. In the present study styrene monomer potently inhibits MAO-A activity, but not MAO-B activity, in monkey brain mitochondria in vitro. These results indicate the inhibiting action of styrene differs depending on animal species and MAO isoforms. Copyright (C) 2000 Elsevier Science Ireland Ltd.

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  • Day/night variation of 5-hydroxyindole acetic acid concentration in rat cerebrospinal fluid after acute and long-term administration of a selective serotonin reuptake inhibitor, fluvoxamine

    T Egashira, F Takayama, Y Yamanaka, K Takada, H Takeda, T Matsumiya

    JAPANESE JOURNAL OF PHARMACOLOGY   83 ( 4 )   344 - 347   2000.8

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    When 30 mg/kg, p.o. of fluvoxamine, a selective serotonin reuptake inhibitor, was administered, significant increases of 3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxy indole-3-acetic acid (5-HIAA) contents in rat cerebrospinal fluid (CSF) were observed from two days after administration of fluvoxamine in both the light and dark periods and in the dark period of the light/dark cycle, respectively. In long-term treatment with 15 mg/kg, p.o. of fluvoxamine, the level of MHPG in CSF exhibited no difference, whereas the levels of 5-HIAA showed a significant increase during the light periods. These results suggest that fluvoxamine enhances the 5-HT system, but only with long-term treatment.

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  • Antioxidant and hepatoprotective actions of the medicinal herb Artemisia campestris from the Okinawa Islands

    Y Aniya, M Shimabukuro, M Shimoji, M Kohatsu, MA Gyamfi, C Miyagi, D Kunii, F Takayama, T Egashira

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   23 ( 3 )   309 - 312   2000.3

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    The antioxidant action of Artemisia campestris was examined in vitro and in vivo. A water extract of A. campestris showed a strong scavenging action of 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and superoxide anion radicals. When the extract was given intraperitoneally to mice prior to carbon tetrachloride (CCl4) treatment, CCl4-induced liver toxicity, as seen by an elevation of serum aspartate aminotransferase and alanine aminotransferase activities, was significantly reduced. Depression of the elevation of serum enzyme levels after CCl4-treatment was also observed by oral administration of the extract. In that case, CCl4-derived lipid peroxidation in the liver was decreased by the extract treatment. These results suggest that the extract of A. campestris scavenges radicals formed by CCl4 treatment resulting in protection against CCl4-induced liver toxicity.

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  • ラット肝虚血再循環時における血中のフリーラジカル関連物質の動態

    江頭 亨, 高山 房子, 山中 康光

    日本薬理学雑誌   115 ( 3 )   67P - 67P   2000.3

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  • 酸化ストレス負荷で惹起された単離肝細胞障害に対するグリチルリチンおよびグリチルレチン酸の保護効果.

    高山房子, 江頭 亨, 山中康光

    薬理と治療   2000

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  • Changes in monoamine metabolites concentrations in rat cerebrospinal fluid after acute and long-term administration of a selective serotonin reuptake inhibitor, trazodone

    T Egashira, F Takayama, Y Yamanaka

    PHARMACOLOGICAL RESEARCH   40 ( 6 )   503 - 508   1999.12

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    In order to clarify the mechanism of the antidepressive effects of trazodone, a selective serotonin reuptake inhibitor, we investigated the dynamics of monoamine metabolites in cerebrospinal fluid (CSF) of free-moving conscious rats by acute and long-term treatment with trazodone. When 100 mg kg(-1) p.o. of trazodone were administered, a significant increase of 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration was soon observed in the light period of the light/dark cycle, and a significant decrease of dihydroxy phenyl acetic acid (DOPAC) concentration was observed during the 2 days after administration of trazodone; in contrast, the homovanilic acid (HVA) level was increased. However, we detected no significant changes in the 5-hydroxy indole-3-acetic acid (5-HIAA) concentration during the 3 days. In the case of long-term treatment with 50 mg kg-l, p.o. of trazodone, the levels of MHPG, DOPAC and HVA exhibited no difference when compared with values obtained during saline treatment in either the light or dark period, whereas the levels of 5-HIAA showed a significant increase during the light period. These findings suggest that a long-term treatment with trazodone enhances the serotonergic neurons. (C) 1999 Academic Press.

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  • The inhibition of monoamine oxidase activity by various antidepressants: Differences found in various mammalian species

    T Egashira, F Takayama, Y Yamanaka

    JAPANESE JOURNAL OF PHARMACOLOGY   81 ( 1 )   115 - 121   1999.9

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    The effects of the antidepressant drugs zimeldine, imipramine, maprotiline or nomifensine on mitochondrial monoamine oxidase (MAO) activity in mouse, rat, dog and monkey brains were compared in vitro. Mouse, rat, dog and monkey brain MAO-B activities were inhibited by zimeldine more potently than MAO-A activity. Imipramine inhibited MAO-B more potently than MAO-A activity in mouse and rat brains. When dog and monkey brains were investigated, MAO-A activity was inhibited more potently than MAO-B activity at high concentrations of imipramine, while at low concentrations, MAO-B activity was more potently inhibited. Maprotiline and nomifensine inhibited mouse and rat brain MAO-B activity more potently than MAO-A activity, while the inverse was true for dog and monkey brains. All four drugs are competitive inhibitors of MAO-A, but noncompetitive inhibitors of MAO-B in all animal brains. The respective K-i values of these reagents for monkey brain MAO-A and MAO-B were low compared to those of mouse, rat and dog. These results indicate that monkey brain MAOs are more sensitive to antidepressant drugs than those in rodent brain.

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  • Monitoring of radical scavenging activity of peroral administration of the Kampo medicine Sho-saiko-to in rats

    T Egashira, F Takayama, Y Yamanaka, Y Komatsu

    JAPANESE JOURNAL OF PHARMACOLOGY   80 ( 4 )   379 - 382   1999.8

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    The Kampo medicine Sho-saiko-to scavenged superoxide anion radicals (O-2(-)), hydroxyl radicals ( OH) and 1,1 -diphenyl-2-picrylhydrazyl (DPPH) radicals in a dose-dependent fashion. We attempted to investigate the transition of free radical scavenging activity in plasma after oral administration of Sho-saiko-to in rats. From the response-time profile, kinetic parameters including values for K-a (absorption rate constant), T-max (peak concentration time), T-1/2 (half life) and MRT (mean residence time) of radical scavenging activity in plasma could be calculated for the O-2(-), .OH and DPPH radicals. These parameters calculated from the dynamics of antioxidation are considered a very meaningful procedure to examine the effects of Sho-saiko-to.

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  • ESR measurement of endogenous nitric oxide in liver and blood of mice subjected to hepatic ischemia-reperfusion

    Fusako Takayama, Toru Egashira, Yasumitsu Yamanaka

    Pathophysiology   6 ( 1 )   45 - 51   1999.4

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    To examine the role of nitric oxide (NO) in liver ischemia-reperfusion injuries, electron spin resonance (ESR) measurements were employed to directly detect NO in the liver and blood of mice subjected to liver ischemia-reperfusion. We used an NO trapping and accumulating reagent, N- (dithiocarboxy)sarcosine/Fe2+ (DTCS/Fe) that specifically binds to NO to form stable NO adduct, (DTCS)/Fe-NO. The DTCS/Fe-NO adduct is detectable by ESR spectrometry at room temperature, giving rise to a characteristic triplet spectrum. The (DTCS)/Fe-NO contents in liver and blood decreased during ischemia, and still more decreased at the early reflow phase. Then, 12 h after reflow onset, the adduct content increased approximately 1.5-fold in the liver and 2.5-fold in the blood compared to that in a non-ischemia group. The fluctuation of liver NO levels may have resulted from a lack of oxygen during ischemia and the scavenging of superoxide anions during the early reflow phase. Therefore, NO levels would result in decline, then a subsequent boost in NO levels as cells respond to the reperfusion-induced damage. Blood endotoxin concentration and serum aspartate oxoglutarate aminotransferase (AST), alanine oxoglutarate aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were significantly higher in the liver ischemia-reperfused group than in the sham-operated group. Pretreatment with N(G)-mono-N-methyl-L- arginine, an NO synthase inhibitor resulted in decreased NO levels to an undetectable level, all the more increased lipid peroxide contents in liver, and the amelioration of hepatic injury induced by 60 min of liver ischemia followed by 60 min of reperfusion. From these results, NO was interpreted to protect against injuries in part to brake the progression of the free radical chain reaction.

    DOI: 10.1016/S0928-4680(98)00037-6

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  • No contribution to lipopolysaccharide-induced hepatic damage in galactosamine-sensitized mice

    Fusako Takayama, Toru Egashira, Yasumitsu Yamanaka

    Journal of Toxicological Sciences   24 ( 1 )   69 - 75   1999.2

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    To investigate the role of nitric oxide (NO) in hepatitis-induced endotoxemia, we injected mice intraperitoneally with 250 mg/kg galactosamine (GalN) and 1 mg/kg lipopolysaccharide (LPS) separately and in combination. NO synthesis increased in a dose-dependent manner with LPS. NO generation at 5 hr after administration of LPS was greater than that at 24 hr. Enhancement of NO generation was demonstrated in mice administered GalN and LPS in combination. A nitrosyl-heme signal in 10,000 g supernatant of liver homogenate, due to cytochrome P450 (P450) combining with NO, NO-P450, was detected at more than ten hr and even more after administration of LPS by electron spin resonance (ESR) measurements at 77°K. The strongest NO-P450 signal and most extreme elevation of aspartate oxoglutarate aminotransferase (AST), alanine oxoglutarate aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum and of lysosomal enzyme activity in plasma were observed in the GalN+LPS group. Their potency was greater than in the 10 mg/kg LPS group, which was even greater than in the LPS 1 mg/kg group. The aniline hydroxylase activity was inversely proportional to NO-P450 signal intensity. It appears that NO might contribute to LPS-induced hepatic damage in GalN-sensitized mice through degeneration and inactivation of liver microsomal enzymes by binding P450 active sites.

    DOI: 10.2131/jts.24.69

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  • グリチルリチンの脳内モノアミン動態に及ぼす影響.

    江頭 亨, 高山房子, 山中康光, 高田 香, 武田弘志, 松宮輝彦

    薬理と治療   1999

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  • 人参養栄湯に関する薬理学的基礎研究。第二報:人参養栄湯長期投与による生体内フリーラジカルおよび過酸化脂質の動態.

    江頭 亨, 池辺あや, 井上美幸, 大山美雪, 成合美穂子, 成迫久美, 田中さおり, 高山房子, 山中康光

    和漢医薬学雑誌   1999

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  • 人参養栄湯に関する薬理学的基礎研究。第一報 :人参養栄湯のフリーラジカル消去作用.

    江頭 亨, 高山房子, 山中康光

    和漢医薬学雑誌   1999

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  • 老齢ラット脳のコリン作動性神経系の神経化学的マーカーの検討 老化,性差,飼育環境

    江頭 亨, 高山 房子, 山中 康光

    神経化学   37 ( 3 )   383 - 383   1998.9

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    Language:Japanese   Publisher:日本神経化学会  

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Presentations

  • 非アルコール性脂肪性肝炎(NASH)随伴サルコペニアリスクに対する藍藻成分の影響

    江崎 茜, 犬飼 修太郎, 黄堂 泰昌, 万倉 三正, 豊田 博, 渡邊 律子, 加太 英明, 高山 房子

    第74回日本酸化ストレス学会 第21回日本NO学会 合同学術集会  2021.5.20 

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    Event date: 2021.5.19 - 2021.5.20

    Presentation type:Poster presentation  

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  • 抗酸化発酵食品 AOB による NAFLD 予防機能 _ 腸管バリア障害と慢性炎症に着目して

    津野 航, 有吉 孝仁, 大倉 朋子, 三宅 歩実, 豊田 博, 渡邊 律子, 高山 房子

    第74回日本酸化ストレス学会 第21回日本NO学会 合同学術集会  2021.5.20 

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    Event date: 2021.5.19 - 2021.5.20

    Language:Japanese   Presentation type:Poster presentation  

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  • メトフォルミンの NAFLD に対する逆ベクト ル作用とミトコンドリア酸化ストレス

    釜谷 春香, 高山 房子, 犬飼 修太郎, 藤原 由理, 豊田 博, 渡邊 律子, 岡田 茂

    第74回日本酸化ストレス学会 第21回日本NO学会 合同学術集会 2021年5月20日  2021.5.19 

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    Event date: 2021.5.19 - 2021.5.20

    Language:Japanese  

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  • 非アルコール性脂肪性肝炎発症・進展への摂取糖質の相違による影響および スピルリナ成分による NASH 予防効果の機序解明

    高山 房子, 河井 花菜子, 野村 彩織, 黄堂 泰昌, 豊田 博, 渡邊 律子, 加太 英明, 万倉 三正

    第73回日本酸化ストレス学会 / 第20回日本NO学会合同学術集会  2020.10.6 

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    Event date: 2020.10.6 - 2020.10.7

    Language:Japanese  

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  • ラン藻成分によるNASH進行リスク低減機能_腸管バリア障害と慢性炎症に着目して

    有吉孝仁,高山房子,大倉朋子 ,犬飼修太郎, 森本龍平,河井花菜子,黒田浩基,豊田博,渡邊律子,黄堂泰昌, 岡田茂

    第72回日本酸化ストレス学会学術集会  日本酸化ストレス学会

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    Event date: 2019.6.26 - 2019.6.27

    Language:Japanese   Presentation type:Poster presentation  

    Venue:札幌市  

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  • A fermented grain food mixture (AOB) protects NASH progression International conference

    Fusako Takayama, Takahito Ariyoshi, Yuri Fujihara1), Ritsuko Watanabe, Hiroshi Toyoda, Hideaki Kabuto, Shigeru Okada

    The 9th Biennial Meeting of Society for Free Radical Research-Asia (SFRR-Asia 2019)(Kyoto)  Free Radical Research-Asia

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    Event date: 2019.4.4 - 2019.4.6

    Language:English   Presentation type:Poster presentation  

    Venue:Kyoto  

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  • Spirulina and its ingredient, pterin derivative ameliorate non-alcoholic steatohepatitis model rats International conference

    Yuri Fujihara, Yasumasa Kodo, Ritsuko Watanabe, Hiroshi Toyoda, Mitsumasa Mankura, Hideaki Kabuto, Shigeru Okada , Fusako Takayama

    The 9th Biennial Meeting of Society for Free Radical Research-Asia (SFRR-Asia 2019)(Kyoto)  Free Radical Research-Asia

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    Event date: 2019.4.4 - 2019.4.6

    Language:English   Presentation type:Poster presentation  

    Venue:Kyoto  

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  • NASHに対する抗酸化発酵食品AOB の効果:高糖・高脂肪摂餌ラットで惹起される腸内環境異常に着目して

    有吉孝仁,河井花奈子,黒田浩基,藤原由理,大倉智子, 森本龍平, 犬飼修太郎,豊田 博, 渡邊 律子, 高山 房子

    第18回AOB研究会  2018  AOB研究会

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    Event date: 2018.6.16

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都ホテルオークラ (京都市)  

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  • :Blue algae and its ingredients ameliorate NASH, with synchronous relief of oxidative stress and inflammation in gut of rats

    2018 

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    Event date: 2018.5.17 - 2018.5.18

    Language:Japanese   Presentation type:Poster presentation  

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  • 非アルコール性脂肪性肝炎(NASH)合併サルコペニア病態に対する藍藻成分と分岐鎖アミノ酸の効果

    犬飼 修太郎, 高山 房子, 黄堂 泰昌, 豊田 博, 渡邊 律子, 古谷 満寿美, 万倉 三正, 加太 英明, 岡田 茂

    第71回日本酸化ストレス学会学術集会  2018  日本酸化ストレス学会

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    Event date: 2018.5.17 - 2018.5.18

    Language:Japanese   Presentation type:Poster presentation  

    Venue:仙台市  

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  • 非アルコール性脂肪性肝炎(NASH)合併サルコペニアに対する 杜仲葉エキスの影響

    近藤 史織, 高山 房子, 細尾 信悟, 杉万 直, 平田 哲也, 山口 康代, 山崎 寛生, 川崎 博己, 豊田 博, 渡邊 律子, 加太 英明, 万倉 三正, 大倉 朋子, 藤原 由理, 吉野 真帆, 江頭 亨, 岡田 茂

    日本杜仲研究会 第12回 定期大会  2017  日本杜仲研究会

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    Event date: 2017.7.29

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京国際フォーラム (千代田区)  

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  • 非アルコール性脂肪性肝炎に対する杜仲葉エキスと分岐鎖アミノ酸の予防効果

    藤原 由理, 高山 房子, 江頭 亨, 細尾 信悟, 杉万 直, 平田 哲也, 山口 康代, 山崎 寛生, 川崎 博己, 豊田 博, 渡邊 律子, 加太 英明, 万倉 三正, 岡田 茂

    第70回日本酸化ストレス学会学術集会  2017  日本酸化ストレス学会

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    Event date: 2017.6.28 - 2017.6.29

    Language:Japanese   Presentation type:Poster presentation  

    Venue:仙台市  

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  • NASH病態ラットにおける腸管の形態学的変化とCYP変動について? −NASH進展リスク軽減機能の作用点となり得るか?−

    大倉 朋子, 高山 房子, 江頭 亨, 細尾 信悟, 杉万 直, 平田 哲也, 山口 康代, 山崎 寛生, 川崎 博己, 豊田 博, 渡邊 律子, 加太 英明, 万倉 三正, 岡田 茂

    第70回日本酸化ストレス学会学術集会  日本酸化ストレス学会

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    Event date: 2017.6.28 - 2017.6.29

    Language:Japanese   Presentation type:Poster presentation  

    Venue:仙台市  

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  • Protective effects of Eucommia ulmoides leaf extract and its costituent, asperuloside on non-alcoholic steatohepatitis (NASH)

    2017 

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    Event date: 2017.3.24 - 2017.3.27

    Language:Japanese   Presentation type:Poster presentation  

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  • Does Eucommia ulmoides leaf extract have an effect on the progression ri sk of sarcopenia as a complication of non-alcoholic steatohepatitis?

    2017 

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    Event date: 2017.3.24 - 2017.3.27

    Language:Japanese   Presentation type:Poster presentation  

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  • 非アルコール性脂肪性肝炎に対する藍藻類成分の効果

    Saori Nomura, Aya Yoshii, Shigeru Okada, Ritsuko Watanabe, Hiroshi Toyoda, Hideaki Kabuto, Tomoko Yamanushi, Mitsumasa Mankura, Yasumasa Kodo, Toru Egashira, Akitane Mori, Fusako Takayama

    第69回日本酸化ストレス学会学術集会  2016  日本酸化ストレス学会

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    Event date: 2016.8.30 - 2016.8.31

    Language:Japanese   Presentation type:Poster presentation  

    Venue:仙台市  

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  • 非アルコール性肝炎(NASH)に対する杜仲葉エキスの予防機能

    高山 房子, 細尾 信悟, 平田 哲也, 山口 康代, 山崎 寛生, 和田 篤敬, 川崎 博己, 豊田 博, 渡邊 律子, 山主 智子, 加太 英明, 万倉 三正, 岡田 茂

    第16回日本抗加齢医学会総会  2016  日本抗加齢医学会

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    Event date: 2016.6.10 - 2016.6.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:パシフィコ横浜 (横浜市)  

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  • Spirulina components alleviate NASH progression to intervene inflammation in progressive

    Nomura, Saori, , Yoshii, Aya, Okada, Shigeru, Watanabe, Ritsuko, Toyoda, Hiroshi, Kabuto, Hideaki, Yamanushi, Tomoko, Mankura, Mitsumasa, Kodo, Yasumasa, Egashira, Toru, Mori, Akitane, Takayama, Fusako

    第89回日本薬理学会年会  2016  日本薬理学会

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    Event date: 2016.3.9 - 2016.3.11

    Language:English   Presentation type:Poster presentation  

    Venue:横浜市  

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  • DHA経口摂取による右鬱血性心不全ラット心筋細胞イオンチャネル発現の変化

    Saori Nomura, Aya Yoshii, Shigeru Okada, Ritsuko Watanabe, Hiroshi Toyoda, Hideaki Kabuto, Tomoko Yamanushi, Mitsumasa Mankura, Yasumasa Kodo, Toru Egashira, Akitane Mori, Fusako Takayama

    日本脂質栄養学会第24回大会  2015  日本脂質栄養学会

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    Event date: 2015.8.28 - 2015.8.29

    Language:Japanese   Presentation type:Poster presentation  

    Venue:佐賀市  

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  • 非アルコール性脂肪性肝炎に対するスピルリナ成分の有効性と栄養エネルギー代謝破綻への影響

    Saori Nomura, Aya Yoshii, Shigeru Okada, Ritsuko Watanabe, Hiroshi Toyoda, Hideaki Kabuto, Tomoko Yamanushi, Mitsumasa Mankura, Yasumasa Kodo, Toru Egashira, Akitane Mori, Fusako Takayama

    第68回日本酸化ストレス学会学術集会  2015  日本酸化ストレス学会

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    Event date: 2015.6.11 - 2015.6.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:鹿児島市  

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  • 症状改善薬投与に伴うパーキンソン病モデルマウスの病態進行に及ぼすスクアレンの影響 抗酸化活性への影響

    加太 英明, 山主 智子, 照屋 茜, 問田 真由, 香川 穂輝, 高山 房子, 万倉 三正

    第68回日本栄養・食糧学会大会  2014  日本栄養・食糧学会

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    Event date: 2014.5.30 - 2014.6.1

    Language:English   Presentation type:Poster presentation  

    Venue:札幌市  

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  • Spirulina platensis and its ingredient prevent NASH to attenuate oxidative stress from mitochondrial energy metabolism and chronic inflammation followed by metabolic turnover alteration. International conference

    Aya Yoshii, Fusako Takayama, Yasumasa Kodo, Ritsuko Watanabe, Hiroshi Toyoda, Mitsumasa Mankura, Toru Egashira, Hideaki Kabuto, Tomoko Yamanushi, Yuji Kurosaki, Shigeru Okada, Akitane Mori

    The Oxygen Club California (OCC), the 2014 World Congress on Oxidants and Antioxidants In Biology  2014 

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    Event date: 2014.5.7 - 2014.5.10

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  • Intervention of Spirulina platensis and phycocyanin in ferric nitrilotriacetate- induced renal oxidative damage and inflammatory alteration in mice. International conference

    Aya Yoshii, Fusako Takayama, Yasumasa Kodo, Ritsuko Watanabe, Hiroshi Toyoda, Mitsumasa Mankura, Toru Egashira, Hideaki Kabuto, Tomoko Yamanushi, Yuji Kurosaki, Shigeru Okada, Akitane Mori

    The Oxygen Club California (OCC), the 2014 World Congress on Oxidants and Antioxidants In Biology  2014 

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    Event date: 2014.5.7 - 2014.5.10

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  • Mechanism of spirulina platensis efficacy against non-alcoholic steatoepatitis model rats. International conference

    Aya Yoshii, Fusako Takayama, Yasumasa Kodo, Ritsuko Watanabe, Hiroshi Toyoda, Mitsumasa Mankura, Toru Egashira, Hideaki Kabuto, Tomoko Yamanushi, Yuji Kurosaki, Shigeru Okada, Akitane Mori

    International symposium on Free Radical Resarch: Contribution to Medicine. 2010  2014 

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    Event date: 2014.3.23 - 2014.3.26

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  • Spirulina attenuates ferric nitrilotriacetate-induced renal oxidative damage in mice. International conference

    Fusako Takayama, Manaka Mine, Yasumasa Kodo, Ritsuko Watanabe, Hiroshi Toyoda, Hideaki Kabuto, Tomoko Yamanushi, Mitsumasa Mankura, Akitane Mori, Shigeru Okada

    International symposium on Free Radical Resarch: Contribution to Medicine. 2010  2014 

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    Event date: 2014.3.23 - 2014.3.26

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  • 非アルコール性脂肪性肝炎に対するスピルリナ成分の有効性とその機序の検討

    吉井 彩,高山房子,呉 艶,Panot TANGSUTYARIT, 萩森 健太, 豊田 博,渡邊 律子, 黄堂 泰昌, 加太 英明, 山主 智子, 黒崎 勇二, 岡田 茂, 森 昭胤

    第66回 日本酸化ストレス学会学術集会  2013  日本酸化ストレス学会

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    Event date: 2013.6.13 - 2013.6.14

    Presentation type:Poster presentation  

    Venue:名古屋市 ウインクあいち  

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  • 高純度エイコサペンタエン酸及びドコサヘキサエン酸経口投与によるラット右鬱血性心不全の予防効果

    加太 英明, 平川 栄一郎, Janjua Najma, 高山 房子, 万倉 三正

    第67回日本栄養・食糧学会大会  2013  日本栄養・食糧学会

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    Event date: 2013.5.24 - 2014.5.26

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋市  

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  • Nicotine facilitates the reinnervation of injured perivascular nerves

    Kenta Hagimori1, Hidetoshi Fujiwara, Panot Tangsucharit, Hiromu Kawasaki, Fusako Takayama

    第86回 日本薬理学会年会  2013  社団法人 日本薬理学会

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    Event date: 2013.3.21 - 2013.3.23

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福岡市 岡山大学 鹿田キャンパス  

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  • 血管周囲神経損傷ラットにおけるニコチンの交感神経再分布促進作用機序に関する研究

    萩森 健太,藤原 秀敏,川? 博已,高山 房子

    第18回 創薬・薬理フォーラム岡山  2012  岡山創薬・薬理研究会

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    Event date: 2012.12.22

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:岡山市 岡山大学 鹿田キャンパス  

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  • M1/M3 acetylcholine receptors mediate acetylcholine-induced endothelium-independent and CGRPergic nerve-mediated vasodilation in rat mesenteric arteries

    Panot Tangsucharit, Poungrat Pakdeechote, Shingo Takatori, Fusako Takayama and Hiromu Kawasaki

    第18回 創薬・薬理フォーラム岡山  2012  岡山創薬・薬理研究会

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    Event date: 2012.12.22

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:岡山市 岡山大学 鹿田キャンパス  

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  • Profile of protective effects of Hinase oyster preparation and its constitutional n-3 PUFA on non-alcoholic steatohepatitis International conference

    Fusako Takayama, Mitsumasa Mankura, Toru Egashira, Enn Go, Aya Yoshi, Shigeru Okada and Akitane Mori

    Bioactive Okayama 2012  2012  Okayama Bioactive Research Society

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    Event date: 2012.9.13 - 2012.9.14

    Language:English   Presentation type:Oral presentation (general)  

    Venue:Okayama University 50th Anniversary Hall, 1-1-1 Tsushima-naka Kita-ku, Okayama  

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  • ラット腸間膜動脈血管周囲神経損傷モデルにおけるnicotineの神経再分布促進作用

    萩森健太、藤原秀敏、高取真吾、高山房子、川崎?博已

    日本薬学会第132年会  2012  公益社団法人 日本薬学会

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    Event date: 2012.3.28 - 2012.3.31

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:北海道札幌市 北海道大学  

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  • Anti-oxidative stress and anti-inflammatory effects of oyster preparation on NASH model rats International conference

    Takao Kaneyuki, Chengzhu Zhao, Mitsumasa Mankura, Toru Egashira, Hiromu Kawasaki, Shigeru Okada, and Akitane Mori, Fusako Takayama

    11th Asian Congress of Nutrition  2011 

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    Event date: 2011.7.13 - 2011.7.16

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  • 非アルコール性脂肪性肝炎に対する抗酸化および抗炎症機能を介したスピルリナの効果

    峰 麻奈加、白 穎、黄堂 泰昌、江頭 亨、川? 博己、万倉 三正、岡田 茂、森 昭胤、高山 房子

    第64回日本酸化ストレス学会学術集会  2011  日本酸化ストレス学会

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    Event date: 2011.7.2 - 2011.7.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:ルスツリゾートホテル&コンベンション, 北海道虻田郡 北海道  

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  • Effect of oyster preparation and its consititutional n-3 polyunsaturated fatty acid on NASH through redox balance regulation. International conference

    Chengzhu Zhao, Mitsumasa Mankura, Toru Egashira, Hiromu Kawasaki, Shigeru Okada, Akitane Mori, and Fusako Takayama

    International symposium on Free Radical Resarch: Contribution to Medicine. 2010  2011 

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    Event date: 2011.1.20 - 2011.1.22

    Language:English   Presentation type:Poster presentation  

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  • Effects of spirulina on non-alcoholic steatohpatitis through anti-oxidative and anti-inflammatory mechanisms. International conference

    Fusako Takayama, Wing Pak, Mitsumasa Mankura, Toru Egashira, Hiromu Kawasaki, Yasumasa Kodo, Manaka Mine, Shigeru Okada, Akitane Mori

    International symposium on Free Radical Resarch: Contribution to Medicine. 2010  2011 

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    Event date: 2011.1.20 - 2011.1.22

    Language:English   Presentation type:Poster presentation  

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  • 非アルコール性脂肪性肝炎モデルに対する大豆ペプチドとDHAの 有効性に対する研究

    杉本志保、万倉三正、江頭亨、三宅夏樹、川崎博已、岡田茂、森昭胤、高山房子

    第63回日本酸化ストレス学会学術集会  2010  日本酸化ストレス学会

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    Event date: 2010.6.24 - 2010.6.25

    Language:Japanese   Presentation type:Poster presentation  

    Venue:横浜市  

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  • 非アルコール性脂肪性肝炎に対する抗酸化機能を介した スピルリナの効果

    ○峰 麻奈加、高山 房子、白 穎、黄堂 泰昌、万倉 三正、江頭 亨、川崎 博已、岡田 茂、 森 昭胤

    第63回日本酸化ストレス学会学術集会  2010  日本酸化ストレス学会

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    Event date: 2010.6.24 - 2010.6.25

    Language:Japanese   Presentation type:Poster presentation  

    Venue:横浜市  

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  • Beneficial effects of spirulina on non-alcoholic steaeohepatitis model rats by anti-oxidative and anti- inflammatory activities. International conference

    the 2010 World Congress of the Oxygen Club of California  2010 

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    Event date: 2010.3.17 - 2010.3.20

    Presentation type:Oral presentation (general)  

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  • Effects of aqueous extracts from Vitis Coignetiae Pulliat leave on non-alcoholic heatohepatitis model rat. International conference

    the 2010 World Congress of the Oxygen Club of California  2010 

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    Event date: 2010.3.17 - 2010.3.20

    Presentation type:Oral presentation (general)  

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  • Protective effects of SAIDO-PS501 on stress-induced acute gastric mucosal lesion in rats International conference

    Shinki Murakami, *Fusako Takayama, Toru Egashira, Mitsumasa Mankura, Mitsuko Imao, Hiromu Kawasaki, Shigeru Okada and Akitane Mori

    SFRBM's 16th Annual Meeting  2009 

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    Event date: 2009.11.18 - 2009.11.24

    Presentation type:Poster presentation  

    Venue:San Francisco, California USA  

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  • Anti-oxidative and anti-inflammatory effects of oyster on NASH model rats International conference

    Chengzhu Zhao, Fusako Takayama, Mitsumasa Mankura, Toru Egashira, Hiromu Kawasaki, Shigeru Okada, and Akitane Mori

    SFRBM's 16th Annual Meeting  2009 

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    Event date: 2009.11.18 - 2009.11.24

    Presentation type:Poster presentation  

    Venue:San Francisco, California USA  

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  • Anti-oxidative and anti-inflammatory effects of spirulina and its component on non-alcoholic steatohepatitis model rats International conference

    SFRBM's 16th Annual Meeting  2009 

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    Event date: 2009.11.18 - 2009.11.23

    Language:English   Presentation type:Poster presentation  

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  • 学生視点からの病院実務実習における満足度調査

    長谷川あずさ、高山 房子、川崎 博已

    第19回医療薬学会年会  2009 

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    Event date: 2009.10.24 - 2009.10.25

    Presentation type:Oral presentation (general)  

    Venue:長崎市  

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  • 虚血-再灌流腎障害ラットにおける機能性食品の効果とグアニジノ化合物惹起白血球プライミング抑制作用

    高山房子、杉本志保、長谷川あずさ、川崎 博已、森 昭胤

    第30回グアニジノ化合物研究会・総会  2009  グアニジノ化合物研究会・総会

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    Event date: 2009.10.9 - 2009.10.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:筑波  

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  • 急性胃粘膜病変に対するSAIDO-PS501の予防効果

    村上真樹、*高山房子、江頭 亨、今尾充子、万倉三正、川崎博己、岡田 茂、森 昭胤

    第62回日本酸化ストレス学会学術集会  2009 

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    Event date: 2009.6.11 - 2009.6.12

    Presentation type:Poster presentation  

    Venue:福岡市  

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  • スピルリナ成分による非アルコール性脂肪性肝炎(NASH)リスク低減機能メカニズムについて

    村白 穎、*高山 房子、黄堂 泰昌、万倉 三正、江頭 亨、川崎 博已、岡田 茂、森 昭胤

    第62回日本酸化ストレス学会学術集会  2009 

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    Event date: 2009.6.11 - 2009.6.12

    Presentation type:Poster presentation  

    Venue:福岡市  

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  • ω3系多価不飽和脂肪酸DHAの栄養エネルギー代謝改善作用と抗酸化ストレス作用ついて

    日高祐樹、高山房子、万倉三正、江頭亨、川崎博已、森昭胤

    第62回日本酸化ストレス学会学術集会  2009  日本酸化ストレス学会

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    Event date: 2009.6.11 - 2009.6.12

    Presentation type:Poster presentation  

    Venue:福岡市  

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  • The effects of DHA for experimental NASH model rats International conference

    Takao KANEYUKI, *Fusako TAKAYAMA, Nagao TOTANI, Kazuo NAKAMOTO, Yuki HIDAKA, Mitsumasa MANURA, Akitane MORI

    Niigata World Forum on Foods and Flowers 2008  2008 

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    Event date: 2008.11.29 - 2008.11.30

    Presentation type:Poster presentation  

    Venue:新潟市  

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  • Effect of Spirulina on experimental non-alcoholic steatohepatitis model rats International conference

    Pak Wing , Fusako Takayama, Mitsumasa Mankura, Toru Egashira, Yasumasa Kodo, Akitane Mori

    SFRBM's 15th Annual Meeting  2008 

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    Event date: 2008.11.19 - 2008.11.23

    Presentation type:Poster presentation  

    Venue:Indianapolis, Indiana USA  

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  • Effect of SAIDO-PS501 on non-alcoholic steatohepatitis model rats International conference

    Shinki Murakami , Fusako Takayama, Kazuo Nakamoto, Mitsumasa Mankura, Toru Egashira, Mitsuko Imao, Hiromu Kawasaki, Akitane Mori

    SFRBM's 15th Annual Meeting  2008 

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    Event date: 2008.11.19 - 2008.11.23

    Presentation type:Poster presentation  

    Venue:Indianapolis, Indiana USA  

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  • Effect of the fermented green tea on body fat accumulation in rats fed a high-fat diet International conference

    Yuki Hidaka, *Fusako Takayama, Kazuo Nakamoto, Hiromu Kawasaki, Mitsumasa Mankura and Akitane Mori

    SFRBM's 15th Annual Meeting  2008 

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    Event date: 2008.11.19 - 2008.11.23

    Presentation type:Poster presentation  

    Venue:Indianapolis, Indiana USA  

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  • Preventive effect of FGTE against an experimental NASH model rats International conference

    Kazuo Nakamoto, *Fusako Takayama, Mitsumasa Mankura, Tetsuya Ogino, Utsumi kozo, Akitane Mori

    SFRBM's 15th Annual Meeting  2008 

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    Event date: 2008.11.19 - 2008.11.23

    Presentation type:Poster presentation  

    Venue:Indianapolis, Indiana USA  

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  • 腎虚血‐再灌流誘発性急性腎不全モデルに対するDHA とヤマブドウ葉水抽出物の機能性と併用効果に関する研究

    宮城晃子、*高山房子、長谷川あずさ、川崎博已、江頭亨、万倉三正、植木啓司、岡田茂、森昭胤

    第47回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会  2008 

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    Event date: 2008.11.8 - 2008.11.9

    Presentation type:Oral presentation (general)  

    Venue:岡山市  

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  • Nerve growth factor(NGF) のマウス腫 瘍増殖抑制効果

    合田光寛 、能木沙織 、網谷 慶介 、芳原成美 、北村佳久 、*高山房子 、 川崎博己

    第47回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会  2008 

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    Event date: 2008.11.8 - 2008.11.9

    Presentation type:Oral presentation (general)  

    Venue:岡山市  

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  • 腎虚血?再灌流誘発性急性腎不全モデルに対する甘草抽出物と緑茶発酵物の機能性と併用効果に関する研究

    杉本志保、*高山房子、万倉三正、中本賀寿夫、川崎博已、江頭亨、岡田茂、森昭胤

    第47回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会 

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    Event date: 2008.11.8 - 2008.11.9

    Presentation type:Oral presentation (general)  

    Venue:岡山市  

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  • ヤマブドウ葉水抽出物の非アルコール性脂肪性肝炎に対する効果

    長谷川 あずさ、高山 房子、川? 博已、中本 賀寿夫、万倉 三正、岡田 茂、森 昭胤

    第113回日本薬理学会近畿部会  2008 

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    Event date: 2008.6.20

    Presentation type:Oral presentation (general)  

    Venue:岡山市  

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  • 緑茶発酵物水抽出物の非アルコール性脂肪性肝炎(NASH)モデルラットに対する予防効果について

    中本 賀寿夫、高山 房子、万倉 三正、川崎 博已、森 昭胤

    第61回日本酸化ストレス学会学術集会  2008 

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    Event date: 2008.6.19 - 2008.6.20

    Presentation type:Poster presentation  

    Venue:京都市  

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  • 非アルコール性脂肪性肝炎(NASH)モデルラットに対するスピルリナ投与の効果について

    白 穎 、*高山 房子、 万倉 三正 、黄堂 泰昌 、川崎 博已 、 岡田 茂、 森 昭胤

    第61回日本酸化ストレス学会学術集会  2008 

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    Event date: 2008.6.19 - 2008.6.20

    Presentation type:Poster presentation  

    Venue:京都市  

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  • 非アルコール性脂肪性肝炎(NASH) モデルラットに対するSAIDO-PS501の有効性に関する薬理学的研究

    村上真樹、*高山房子、中本賀寿夫、万倉三正、今尾充子、川崎博已、森 昭胤

    第61回日本酸化ストレス学会学術集会  2008 

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    Event date: 2008.6.19 - 2008.6.20

    Presentation type:Poster presentation  

    Venue:京都市  

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  • ラット腸間膜動脈血管の血管周囲交感神経を介するCGRP 神経性血管弛緩反応におけるproton の関与

    宮下智子、平井和浩、北村佳久、*高山房子、川?博己

    第112回 日本薬理学会近畿部会  2007 

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    Event date: 2007.11.16

    Venue:大阪市  

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  • 腎性高血圧ラット腸間膜動脈における血管周囲一酸化窒素含有神経機能変化

    小山敏広、庄司知世、畑中由香子、合田光寛、芳原成美、*高山房子、川崎博己

    第112回 日本薬理学会近畿部会  2007 

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    Event date: 2007.11.16

    Venue:大阪市  

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  • 非アルコール性脂肪性肝炎 (NASH) に対するDHAの効果に関する研究

    井原啓子、*高山 房子、 川崎 博己、中本 賀寿夫、万倉 三正、森 昭胤

    第46回 日本薬学会中国四国支部学術大会  2007 

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    Event date: 2007.10.10 - 2007.10.11

    Venue:高知市  

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  • ヤマブドウ葉成分の新規NASH病態モデルに対する効果

    長谷川 あずさ、*高山 房子、 川崎 博己、中本 賀寿夫、万倉 三正、岡田 茂、森 昭胤

    第46回 日本薬学会中国四国支部学術大会  2007 

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    Event date: 2007.10.10 - 2007.10.11

    Venue:高知市  

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  • 血管周囲神経ー神経伝達におけるプロトンの関与

    平井和浩、宮下智子、北村佳久、*高山 房子、川崎 博己

    第46回 日本薬学会中国四国支部学術大会  2007 

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    Event date: 2007.10.10 - 2007.10.11

    Venue:高知市  

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  • フルクトース負荷ラットにおけるインスリン抵抗性病態の血管周囲神経機能の解析

    細田美穂、薮前奈々、座間味義人、*高山 房子、 川崎 博己

    第46回 日本薬学会中国四国支部学術大会  2007 

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    Event date: 2007.10.10 - 2007.10.11

    Venue:高知市  

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  • Effects of fermented green tea extract on a new experimental non-alcoholic steatohepatitis model rat. International conference

    * Fusako Takayama, Kazuo Nakamoto, Mitsumasa Mankura, Tetsuya Ogino, Takao Kaneyuki, Asanuma Masato, Shigeru Okada, Akitane Mori

    Diet and Optimum Health Conference  2007 

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    Event date: 2007.5.16 - 2007.5.19

    Venue:Portland, Oregon  

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  • Radical scavenging activity of fermented green tea extract.

    Kazuo Nakamoto, *Fusako Takayama, Mitsumasa Mankura, Takao Kaneyuki, Akitane Mori

    Diet and Optimum Health Conference  2007 

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    Event date: 2007.5.16 - 2007.5.19

    Venue:Portland, Oregon  

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  • Nerve growth factor (NGF) の血管周囲神経再分布作用におけるアンジオテンシン タイプ2 (AT2R) の役割

    吉田 菜三夏、横溝 綾子、合田 光寛、大内田 守、清水 憲二、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • NASHモデルラットの肝ミトコンドリアからのフリーラジカル産生に対する茶発酵物の効果

    中本 賀寿夫、*高山 房子、大呂 真史、森田 圭、白 頴、川崎 博己、金行 孝雄、万倉 三正、岡田 茂、森 昭胤

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • 高血圧ラット腸間膜動脈において一酸化窒素含有神経は交感神経伝達を調節する

    小山 敏広、庄司 知代、畑中 由香子、合田光寛、芳原 成美、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • 神経性血管反応に及ぼす様々なインスリン濃度での食後高血糖の影響

    座間味 義人、高取 真吾、山脇 康祐、宮下 智子、薮前 奈々、*高山 房子、見尾 光庸、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • ラット腸間膜動脈のメトキサミン収縮に対する内皮依存性抑制の加齢による減弱と杜仲葉エキス長期投与による改善

    Jin Xin、音無 由紀子、坪井 崇、川村 直美、田川 智慧、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • Matrigel血管新生における血管周囲神経の分布

    能木 沙織、合田 光寛、網谷慶介、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • L-NAME前処置した脊髄穿刺ラットにおけるヒスタミンによる心血管反応

    山脇 康祐、奥畑 智、座間味 義人、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • 脊髄穿刺ラットの脊髄刺激による血管反応に及ぼす一酸化窒素合成酵素阻害薬の影響

    山脇 康祐、奥畑 智、座間味 義人、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • 高血圧ラット腸間膜動脈におけるカルシトニン遺伝子関連ペプチド含有神経と一酸化窒素含有神経による血管緊張度調節

    小山 敏広、庄司 知代、畑中 由香子、合田光寛、芳原 成美、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • ケトライド系抗菌薬テリスロマイシンは血管周囲交感神経伝達を抑制する

    畑中 由香子、小山 敏広、芳原 成美、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • ラット腸間膜血管床における内皮細胞除去によるcGMPを介す血管弛緩反応増強の機序

    岩谷 有希子、能木 沙織、沼 裕美、*高山 房子、見尾 光庸、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • 神経成長因子 (NGF) のマウス腫瘍増殖抑制効果

    合田 光寛、能木 沙織、網谷慶介、芳原 成美、北村 佳久、*高山 房子、川崎 博己

    第80回日本薬理学会年会  2007 

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    Event date: 2007.3.14 - 2007.3.16

    Venue:名古屋市  

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  • 加齢に伴うラット腸間膜動脈のメトキサミン収縮に対する内皮依存性抑制の減弱と杜仲葉エキス長期投与による改善

    金?, 音無由紀子, 坪井崇, 川村直美, 田川智恵, *高山房子, 川崎博己

    日本薬理学会近畿部会110回  2006 

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    Event date: 2006.11.10

    Venue:京都  

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  • マウス腫瘍増殖に対する神経成長因子 (NGF) の抑制効果

    合田光寛、能木沙織、網谷慶介、芳原成美、北村佳久、高山房子、川崎博己

    第110回 日本薬理学会近畿部会  2006 

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    Event date: 2006.11.10

    Venue:京都  

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  • Nerve growth factor (NGF) の血管周囲神経再分布作用におけるアンジオテンシン タイプ2受容体 (AT2R) の役割

    吉田菜三夏、横溝綾子、合田光寛、芳原成美、高山房子、 川崎博己

    第110回 日本薬理学会近畿部会  2006 

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    Event date: 2006.11.10

    Venue:京都  

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  • 非アルコール性脂肪性肝炎への赤ブドウ抽出エキスの効果

    森田 圭、大呂真史、中本賀寿夫、高山 房子、万倉三正、川崎博己

    日本薬学会中国四国支部学術大会  2006 

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    Event date: 2006.10.28 - 2006.10.29

    Venue:広島市  

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  • ラット腸間膜動脈血管における膜型グアニル酸シクラーゼを介する血管弛緩反応の内皮細胞除去による増強機序(会議録)

    岩谷有希子, 沼裕美, 能木沙織,*高山房子, 見尾光庸, 川崎博己

    日本薬理学学会年会  2006 

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    Event date: 2006.3.8 - 2006.3.10

    Venue:横浜市  

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  • 脂肪肝ラット低酸素状態負荷による非アルコール性脂肪肝炎病態モデル

    *高山房子、 芳原成美、中本賀寿夫、大呂真史、武田章利、吉田菜三夏、 川崎博己、江頭 亨

    第79回日本薬理学会年会  2006 

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    Event date: 2006.3.8 - 2006.3.10

    Venue:横浜市  

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  • ラット腸間膜動脈抵抗血管におけるTempolの血管反応

    ◇ 中本 賀寿夫、 武田 章利、*高山 房子、川崎博己

    第79回日本薬理学会年会  2006 

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    Event date: 2006.3.8 - 2006.3.10

    Venue:横浜市  

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  • 急性高血糖が神経性血圧調節機能に及ぼす影響

    座間味義人(岡山大学 大学院医歯薬学総合研究科臨床薬学), 高取真吾, 山脇康佑, 宮下智子, *高山房子, 見尾光庸, 川崎博己

    日本薬理学学会年会  2006 

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    Event date: 2006.3.8 - 2006.3.10

    Venue:横浜市  

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  • ニコチンの交感神経性血管弛緩反応における神経ー神経伝達物質としてのprotonの可能性

    張女朱、江口真嗣、*高山房子、川崎博己

    第44回日本薬学会・日本病院薬剤師会 中四国支部学術大会  2005 

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    Event date: 2005.11.12 - 2005.11.13

    Venue:松山市  

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  • ラット腸間膜動脈収縮に対する内皮由来弛緩因子の抑制的調節と加齢変化

    内堀聡子、音無由紀子、*高山房子、川崎博己

    第44回日本薬学会・日本病院薬剤師会 中四国支部学術大会  2005 

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    Event date: 2005.11.12 - 2005.11.13

    Venue:松山市  

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  • 卵黄蛋白由来ペプチドの降圧作用

    青野祥子、野村政孝、金田輝之、羽田尚彦、*高山房子、川崎博己

    第44回日本薬学会・日本病院薬剤師会 中四国支部学術大会  2005 

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    Event date: 2005.11.12 - 2005.11.13

    Venue:松山市  

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  • 無麻酔無拘束ラットにおける一酸化窒素合成酵素阻害薬L-NAME静脈内投与による昇圧反応機序

    花房伸幸、根木真一、川崎博己、*高山房子

    第44回日本薬学会・日本病院薬剤師会 中四国支部学術大会  2005 

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    Event date: 2005.11.12 - 2005.11.13

    Venue:松山市  

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  • 腸間膜動脈抵抗血管の内皮除去による血管弛緩反応の増強作用機序:cGMPを介する反応の変化

    沼 裕美、岩谷有希子、能木沙織、川崎博己、*高山房子

    第44回日本薬学会・日本病院薬剤師会 中四国支部学術大会  2005 

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    Event date: 2005.11.12 - 2005.11.13

    Venue:松山市  

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  • ラット腸間膜動脈抵抗血管における抗酸化剤tempolの血管反応

    武田章利、中本賀寿夫、*高山房子、川崎博己

    第44回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2005 

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    Event date: 2005.11.12 - 2005.11.13

    Venue:松山市  

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  • 脊髄穿刺ラットの血圧反応に及ぼす急性高血糖の影響

    宮下智子、座間味義人、高取真吾、*高山房子、見尾光庸、川崎博己

    第44回日本薬学会・日本病院薬剤師会 中四国支部学術大会  2005 

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    Event date: 2005.11.12 - 2005.11.13

    Venue:松山市  

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  • SOD様活性を示すtempolのラット腸間膜動脈抵抗血管における血管反応

    中本賀寿夫、武田章利、*高山房子、川崎博己

    第108回日本薬理学会近畿部会  2005 

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    Event date: 2005.11.11 - 2005.11.13

    Venue:松山市  

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  • 肝移植後の免疫抑制剤の血中濃度及び臨床検査値の変動推移と酸化ストレス障害に関する検討

    中本賀寿夫、河崎陽一、北村佳久、*高山房子、川崎博己、三宅 悟、柴田和彦、八木孝仁、田中紀章、五味田 裕

    第15回日本医療薬学会年会  2005 

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    Event date: 2005.10.1 - 2005.10.3

    Venue:岡山市  

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  • Ketoprofen誘発光線過敏症に対するラジカル反応の関与

    *高山房子、大呂真史、桑名由記、黒崎勇二、高取真吾、見尾光庸、川崎博己

    第27回日本フリーラジカル学会学術集会  2005 

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    Event date: 2005.6.4

    Venue:岡山市  

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  • 肝移植施行後胆汁うっ滞によるシクロスポリン血中濃度低下が認められた一症例

    中本賀寿夫、河崎陽一、*高山房子、川崎博己、三宅 悟、柴田和彦、八木孝仁、田中紀章、五味田 裕

    第22回日本TDM学会・学術大会  2005 

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    Event date: 2005.5.21 - 2005.5.22

    Venue:宜野湾市  

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  • 脊髄穿刺ラットの血圧反応に及ぼす高血糖の影響

    座間味義人、山脇康佑、高取真吾、*高山房子、見尾光庸、川崎博己

    第78回日本薬理学会年会  2005 

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    Event date: 2005.3.24

    Venue:横浜市  

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  • Adrenomedullinによるラット腸間膜動脈周囲神経の再生分布促進作用

    芳原成美、合田光寛、大塚*高山房子、川崎博己

    第78回日本薬理学会年会  2005 

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    Event date: 2005.3.23

    Venue:横浜市  

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  • ラット腸間膜動脈抵抗血管における内皮除去による血管弛緩反応の増強作用機序:セカンドメッセンジャーの関与

    岩谷有希子、能木沙織、*高山房子、川崎博己

    第78回日本薬理学会年会  2005 

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    Event date: 2005.3.22

    Venue:横浜  

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  • ラット腸間膜動脈抵抗血管におけるヒスタミンによる血管周囲神経を介した血管収縮および弛緩反応

    金 紅花、小山敏広、畑中由香子、*高山房子、川崎博己

    第78回日本薬理学会年会  2005 

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    Event date: 2005.3.22

    Venue:横浜市  

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  • NOS阻害はラット腸間膜動脈周囲交感神経の伝達を促進する

    畑中由香子、芳原成美、金 紅花、丁 敏、小林裕太、*高山房子、川崎博己

    第78回日本薬理学会年会  2005 

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    Event date: 2005.3.22

    Venue:横浜市  

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  • ラット腸間膜動脈抵抗血管におけるヒスタミンの血管反応

    小山敏広、金 紅花、*高山房子、川崎博己

    第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2004 

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    Event date: 2004.4

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  • Ketoprofen誘発光線過敏症に対するラジカル反応の関与についての検討

    大呂真史、桑名由記、*高山房子、川崎博己

    第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2004 

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    Event date: 2004.4

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  • 嚥下障害を有する患者に対する薬学的アプローチ

    桑名由記、小寺訓代、森英樹、出石文男、柴田和彦、五味田裕、*高山房子、川崎博己

    第14回日本医療薬学学会年会  2004 

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    Event date: 2004.4

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  • 経管栄養チューブによる薬剤投与方法の改善について〜簡易懸濁法

    座間味義人、石井雅人、*高山房子、柴田和彦、川崎博己、五味田裕

    第14回日本医療薬学学会年会  2004 

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    Event date: 2004.4

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  • 酸化ストレス誘発単離肝細胞障害へのグリチルリチンおよびグリチルレチン酸の抑制効果について

    吉田菜三夏、*高山房子、桑名由記、座間味義人、中本賀寿夫、大呂真史、山脇康佑、川崎博己

    第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2004 

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    Event date: 2004.4

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  • Adrenomedullinによるラット腸間膜動脈周囲神経の再生促進作用

    合田光寛、芳原成美、大塚*高山房子、川崎博己

    第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2004 

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    Event date: 2004.4

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  • ラット腸間膜動脈抵抗血管の内皮除去による血管弛緩反応増強機序: セカンドメッセンジャーの関与

    能木沙織、岩谷有希子、*高山房子、川崎博己

    第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2004 

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    Event date: 2004.4

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  • 脊髄穿刺ラットの血圧反応に及ぼす高血糖の影響

    山脇康佑、座間味義人、*高山房子、川崎博己

    第43回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2004 

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    Event date: 2004.4

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  • 老齢ラットへの人参養栄湯の長期投与によるフリーラジカル、生体分子過酸化傷害及び生存期間への影響

    *高山房子, 江頭亨

    第26回 日本過酸化脂質・フリーラジカル学会  2002 

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    Event date: 2002.10.31

    Venue:徳島市  

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  • N-Dimethyl-N-(2-phenoxyethyl)-1-dodecanaminium bromide (O-5721) の発毛効果について

    江頭亨, *高山房子, 山中康光

    第75回 日本薬理学会年会  2002 

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    Event date: 2002.3.13 - 2002.3.15

    Venue:熊本市  

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  • Nカフェー酸はα1A-アドレナリン受容体機構を活性化し抗うつ効果を誘発する

    江頭亨, *高山房子, 山中康光, 高田 香, 武田弘志, 松宮輝彦

    第75回 日本薬理学会年会  2002 

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    Event date: 2002.3.13 - 2002.3.15

    Venue:熊本市  

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  • 酸化ストレスに対するムイラプアマの効果

    江頭亨, *高山房子, 山中康光

    第75回 日本薬理学会年会  2002 

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    Event date: 2002.3.13 - 2002.3.15

    Venue:熊本市  

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  • 水浸拘束ストレス負荷ラットにおける血中の酸化的ストレス状態に関する検討

    高山房子, 江頭亨, 山中康光

    第54回 日本薬理学会西南部会  2001 

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    Event date: 2001.11.22

    Venue:福岡市  

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  • 老齢ラットの寿命, 脂質過酸化およびフリーラジカルに対する人参養栄湯の長期投与の効果

    江頭亨, *高山房子, 山中康光

    第74回 日本薬理学会年会  2001 

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    Event date: 2001.3.21 - 2001.3.23

    Venue:横浜市  

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  • 酸化ストレス負荷で惹起された単離肝細胞障害に対するグリチルリチンおよびグリチルレチン酸の保護効果

    *高山房子, 江頭亨, 山中康光

    第53回 日本薬理学会西南部会  2000 

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    Event date: 2000.11.24

    Venue:福岡市  

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  • ラット脳スーパーオキシドデイスムターゼ (SOD)の加齢による変化について,

    江頭亨, *高山房子, 山中康光, 酒井久美子

    第43回 日本神経化学会大会  2000 

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    Event date: 2000.10.18 - 2000.10.20

    Venue:金沢市  

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  • 環境化学物質の脳神経系への影響: スチレンはサル脳モノアミン酸化酵素を阻害する,

    江頭亨, *高山房子, 山中康光

    第27回 日本トキシコロジー学術年会  2000 

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    Event date: 2000.6.29

    Venue:横浜市  

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  • 人参養栄湯のフリーラジカル消去効果に関する研究

    江頭亨, *高山房子, 山中康光

    第73回 日本薬理学会年会  2000 

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    Event date: 2000.3.23 - 2000.3.25

    Venue:横浜市  

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  • コレステロールヒドロペルオキシド負荷により惹起される遊離肝細胞障害

    *高山房子, 江頭亨, 山中康光

    日本過酸化脂質・フリーラジカル学会第23回大会  1999 

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    Event date: 1999.11.26

    Venue:横浜市  

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  • ラット肝虚血再循環時における血中のフリーラジカル関連物質の動態

    江頭亨, *高山房子, 山中康光

    第52回 日本薬理学会西南部会  1999 

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    Event date: 1999.11.20

    Venue:鹿児島市  

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  • B型monoamine oxidase(MAO-B)阻害剤の慢性投与による老齢マウスの寿命延長作用に対するフリーラジカルの関与について

    江頭亨, *高山房子, 山中康光

    第42回 日本神経化学会大会  1999 

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    Event date: 1999.9.16

    Venue:広島市  

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  • 藍藻成分によるNASH軽減作用と腸管の酸化ストレス・透過性亢進と栄養素応答変化に ついて

    第71回日本酸化ストレス学会学術集会  2018 

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  • 杜仲葉エキス成分による非アルコール性脂肪性肝炎(NASH)進行リスク低減機能

    日本薬学会 第137年会  2017 

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  • NASH病態ラットにおける腸管の形態学的変化とCYP変動について  −NASH進展リスク軽減機能の作用点となり得るか?−

    第70回日本酸化ストレス学会学術集会  2017 

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  • 非アルコール性脂肪性肝炎(NASH)病態下サルコペニア進展リスクに対する杜仲葉エキスの影響

    日本薬学会 第137年会  2017 

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  • Intervention of Spirulina platensis and phycocyanin in ferric nitrilotriacetate- induced renal oxidative damage and inflammatory alteration in mice.

    The Oxygen Club California (OCC), the 2014 World Congress on Oxidants and Antioxidants In Biology  2014 

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  • Spirulina platensis and its ingredient prevent NASH to attenuate oxidative stress from mitochondrial energy metabolism and chronic inflammation followed by metabolic turnover alteration.

    The Oxygen Club California (OCC), the 2014 World Congress on Oxidants and Antioxidants In Biology  2014 

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  • Spirulina attenuates ferric nitrilotriacetate-induced renal oxidative damage in mice.

    International symposium on Free Radical Resarch: Contribution to Medicine. 2010  2014 

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  • Mechanism of spirulina platensis efficacy against non-alcoholic steatoepatitis model rats.

    International symposium on Free Radical Resarch: Contribution to Medicine. 2010  2014 

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  • Anti-oxidative stress and anti-inflammatory effects of oyster preparation on NASH model rats

    11th Asian Congress of Nutrition  2011 

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  • Effects of spirulina on non-alcoholic steatohpatitis through anti-oxidative and anti-inflammatory mechanisms.

    International symposium on Free Radical Resarch: Contribution to Medicine. 2010  2011 

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  • Effect of oyster preparation and its consititutional n-3 polyunsaturated fatty acid on NASH through redox balance regulation.

    International symposium on Free Radical Resarch: Contribution to Medicine. 2010  2011 

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  • 腎虚血-再灌流誘発性急性腎不全モデルに対する甘草抽出物と緑茶発酵物の機能性と併用効果に関する研究

    第47回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会  2008 

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  • 腎性高血圧ラット腸間膜動脈における血管周囲一酸化窒素含有神経機能変化

    第112回 日本薬理学会近畿部会  2007 

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  • 嚥下障害を有する患者に対する薬学的アプローチ

    第14回日本医療薬学学会年会  2004 

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Industrial property rights

  • 病態モデル実験動物、病態モデル実験動物の作出方法及び病態モデル実験動物の利用方法

    高山 房子、江頭 亨

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    Application no:2009-528727 

    Patent/Registration no:特許番号5109134 

  • 高度不飽和脂肪酸含有組成物及び該組成物を含有する食品

    万倉 三正、藤井 淳、清水 芳雄、加太 英明、高山 房子、山主 智子

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    Application no:2015-248498 

Research Projects

  • Elucidation of liver mitochondrial metabolism failure and auto-inflammation induced by high‐fat and high sugar diets, to focus on RNA epigenetic

    Grant number:19K11692  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    高山 房子, 合葉 哲也, 古田 和幸, 檜垣 和孝

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    平成31年度に実施予定の実験研究①~③に加え、令和2年実施予定であった「MS生活習慣病の根底の慢性炎症」に関し、腸管上皮バリア機能とインフラマソーム活性化との関係解析に着手した。①【メタボリックシンドローム (MS) 基盤肝疾病の肝異所性脂肪病態「肝細胞内肥満」NAFLD (非アルコール性脂肪性肝疾患, nonalcoholic fatty liver disease)およびその範疇で炎症・線維化進展の著明なNASH[特許第5109134]の両病態動物モデル作製】人道的配慮の基に、ヒト発症リスクに近似させた条件での飼養、すなわち、実験動物Wistar系雄性ラットへの高脂肪・高糖餌による飼養 (4週間)を行った。このラットの半数に、さらに、一過性に「好気的エネルギー代謝に不可欠な酸素の組織供給不足」に近似させるストレスを連日負荷し飼養 (最長6週間) を続けた。実験的飼養期間完了の後、病態の評価・解析用試料として、麻酔を施したラットから臓器・血液試料を採取した。
    ②【栄養性肝疾患NAFLD およびNASH病態進展度の評価】肝障害に対する臨床診断基準 (血液生化学的マーカー、病理組織化学的検査) により病態進展度を評価した。
    ③【栄養の偏りで惹起させたNAFLDと、さらに有酸素性エネルギー代謝の反復性・一過性の軽度な阻害ストレスで惹起させたNASH病態モデルラットの肝臓におけるRNA-エピジェネティックス (RNAメチル化修飾)の解析】メチル化修飾RNA調節でRNA-EGに作動するALKBH活性を左右する補基質と補因子の肝組織中レベルの検討を行った。加えて、RNAメチル化の程度の検討のため、肝組織から抽出したRNA中のN6-メチルアデニン (m6A)量をELISA法により定量した。

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  • Anti-metabolic syndrome study to regulate liver energy metabolism rupture of NASH

    Grant number:25350886  2013.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    TAKAYAMA Fusako, OKADA Shigeru, YOSHII Aya, NOMURA Saori, MANKURA Mitsumasa, SATO Fumi, TOYODA HiROShi, WATANABE Ritsuko, MORI Akitane

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    Grant amount:\4810000 ( Direct expense: \3700000 、 Indirect expense:\1110000 )

    Our previous study exhibited Spirulina platensis worked so well in preventing fibrosis and ameliorating fatty liver of an animal model of non-alcoholic steatohepatitis (NASH). The study indicated the role of epigenetic alteration relating the energy metabolism rupture of liver mitochondria in pathological progress of NASH induced by continuously ingesting high fat and sugar diets and high carbohydrate and by intermittent hypoxemia (similar to sleep apnea syndrome). So this study aimed to explore effects of polyamines to profile the mechanism of polyamines on NASH, to provide therapeutic or preventive agents for therapeutic agent for hepatic dyslipidemia including NASH. The mechanisms of actions were investigated to focus on oxidative injuries, inflammatory reactions and lipid metabolism regulations.

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  • Study of anti-metabolic syndrome effects of cholesteryl ester-n3 PUFA targeting for liver energy metabolism alteration in non-alcoholic steatohepatitis rats.

    Grant number:22500665  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    TAKAYAMA Fusako, OKADA Shigeru, SUGIMOTO Shiho, MANKURA Mitsumasa, SATO Fumi, TOYODA Hiroshi, WATANABE Ritsuko, OKADA Shigeru

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    This study showed that DHA cholesteryl ester and EPA one were useful industrially, as both exerted higher effects to retard the NASH progress approximately 10 times than the respective ethyl ester. By evaluation system to reproduce NASH aggravation by choline deficient high fat diets and besides recurrent intermittent oxygen deficiency stress, it was exhibited that the efficacies resulted from relieving the decreased erythrocyte deformability and the persistent oxidative stress-inflammation.

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Class subject in charge

  • Are chemical substances dangerous for you ? (2021academic year) Third semester  - 金3~4

  • Practice in Clinical and Biopharmaceutical Sciences (2021academic year) Third semester  - その他6~9

  • Practice in Clinical and Biopharmaceutical Sciences (2021academic year) Third semester  - その他6~9

  • Life Science 3 (2021academic year) Late  - その他

  • Physiology 1 (2021academic year) 1st semester  - 水5,水6

  • Physiology 1 (2021academic year) 1st semester  - 水5,水6

  • Physiology 2 (2021academic year) Second semester  - 水5~6

  • Physiology 2 (2021academic year) Second semester  - 水5~6

  • Pathology and Therapeutics (2021academic year) special  - その他

  • Are chemical substances dangerous for you ? (2020academic year) Third semester  - 金3,金4

  • Practice in Clinical and Biopharmaceutical Sciences (2020academic year) Third semester  - その他

  • Practice in Clinical and Biopharmaceutical Sciences (2020academic year) Third semester  - その他

  • Life Science 3 (2020academic year) special  - その他

  • Physiology 1 (2020academic year) 1st semester  - 水5,水6

  • Physiology 1 (2020academic year) 1st semester  - 水5,水6

  • Physiology 2 (2020academic year) Second semester  - 水5,水6

  • Physiology 2 (2020academic year) Second semester  - 水5,水6

  • Pathology and Therapeutics (2020academic year) special  - その他

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Social Activities

  • 「SDGsの達成に向けた岡山大学の取組」として、「科学的プロファイル化天然食資源による栄養改善」の取組

    岡山大学  2018 - 2021.1

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  • 認定NPO法人日本・ミャンマー医療人育成支援協会会員

    Role(s):Organizing member

    認定NPO法人日本・ミャンマー医療人育成支援協会  2009

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    Type:Other

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Media Coverage

  • 梗塞性疾患に対する食品 (ゴーヤ) の有効性解説 TV or radio program

    テレビ朝日  林修先生の今でしょ!講座  2015.7.26

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  • 山ブドウ葉成分の予防医学的機能 TV or radio program

    岡山放送  2007

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