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A Study on Mechanisms of Regional Differences of Side Effects of Hormone Replacement Treatment (HRT)

Research Project

Project/Area Number 16406001
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Gender
Research InstitutionNagoya University

Principal Investigator

HAYASHI Toshio  University Hospital, Assistant Professor, 医学部附属病院, 講師 (80303634)

Co-Investigator(Kenkyū-buntansha) IGUCHI Akihisa  Nagoya University, Graduate School of Mediciene, Professor, 大学院医学系研究科, 教授 (20109763)
SUZUKI Yoshikatsu  Nagoya City University Hospital, Associate Professor, 医学部附属病院, 助教授 (30254288)
KOZAKI Kouiti  Kyourin University School of Mediciene, Associate Professor, 医学部, 助教授 (80272540)
佐久間 一郎  北海道大学, 医学部附属病院, 講師 (40260393)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2004: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsHormone Replacement Therapy / Postmenopausal Women / Comprehensive Geriatric Assessment / Single Nucleotide Polymorphism / Metabolic Syndrome / Atherosclerosis / 遺伝子解析
Research Abstract

Total 1971 postmenopausal women participated the study during 3 years (China: Chengdu n=345, Kumming n=333, Korea: Seoul n=306, Nepal: Katmandu n=156, Iran: Teheran n=201, and Japan: Nagoya n=629). Hormone replacement therapy were applied for 32% of Korean participants, 4% of Japanese, however 0% to other country's peoples. Questionnaires revealed that Japanese. postmenopausal women hope stay indoors, rarely enjoy exercises and have fewer hobbies other than other Asian women. The mean age was 66.77±5.09 yrs, and mean years after menopause was 18.22±7.41 yrs. Compared with data reported, the mean levels of BMI, WC, systolic BP, diastolic BP, and TG tended to be higher.
The prevalence of MetS diagnosed by IDF, NCEP ATPIII, CDS and JPN criteria were 37.34%, 27.31%, 23.29%, and 13.65%, respectively. IDF-MetS had the highest prevalence, whereas JPN-MetS had the lowest one. Although no significant changes of adipocytokines were found among different MetS groups, CDS MetS group tended to have … More the lowest levels of adiponectin, whereas JPN MetS group tended to have the highest levels of TNF alpha and IL-6.
Adipocytokines may be the key factors link visceral adipose accumulation and atherosclerotic diseases, by playing harmful (eg.TNFalpha, IL-6) or protective (eg. adiponectin) roles. In our study, adiponectin levels were revealed to be significant higher in MetS groups than in normal groups. No significant differences were revealed between PMW with MetS and PMW with metabolic disorders.
We are now analyzing the SNPs as above. Almost all genotype showed same pattern among asian countries, there may be some difference in the pattern of SNP of PAI-1, ER a, eNOS etc.
Conclusively, IDF definition for MetS is the most sensitive one to metabolic disorders, whereas JPN and CDS definitions correlate better with CHD and changes of adipocytokines. The supplementation of different dcriteria with adipocytokines may give more meanings to the definition of metabolic syndrome. This study will cover the area of character, attitude and the specificity of asian postmenopausal women and may reveal the difference of atherosclerosis between Asian, American and European women, and may give us the clue of the taylor made therapy for the atherosclerotic diseases of Asian older female. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (38 results)

All 2007 2006 2005 2004 Other

All Journal Article (35 results) Book (3 results)

  • [Journal Article] Risks of CHD identified by different criteria of metabolic snydrome and related changes of adipocytokines in elderly post menopausal women2007

    • Author(s)
      Ding Qunfang, Hayashi T, Matsui-Hirai H, Packiasamy AR, Iguchi A.他2名
    • Journal Title

      J Diabetes and its Complication (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Nitric oxide (NO) is a new clinical biomarker of survival in the elderly patients and its efficacy might be nearly equal to albumin.2007

    • Author(s)
      Osawa M, Hayashi T, Nomura H, Funami J, Miyazaki A, Ignarro LJ, Iguchi A
    • Journal Title

      Nitric Oxide 16

      Pages: 157-163

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 17beta-estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase by High Glucose : Relevance to Postmenopausal Diabetic Cardiovascular Disease.2007

    • Author(s)
      Miyazaki-Akita A, Hayashi T, Ding QF, Shiraishi H, Nomura T, Hattori Y, Iguchi A
    • Journal Title

      J Pharmacol Exp Ther. 320

      Pages: 591-598

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] blantagonist and b2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFα in rat with type II diabetes.2007

    • Author(s)
      Hayashi T, Packiasamy ARJ, Miyazaki-Akita A, Funami J, Matsui-Hirai H, Fukatsu A, Ieuchi A
    • Journal Title

      Life Science 80

      Pages: 592-599

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] High glucose downregulates the number of caveolae in monocytes through oxidative stress from NADPH oxidase : Implications for atherosclerosis.2007

    • Author(s)
      Hayashi T, Juliet PA, Miyazaki A, Ignarro LJ, Iguchi A
    • Journal Title

      Biochim Biophys Acta 1772

      Pages: 364-372

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Nitric oxide (NO) metabolites are associated with survival in older patients-comparison of its efficacy with established markers.2007

    • Author(s)
      Hayashi T, Nomura H, Osawa M, Miyazaki A, Funami J, Matsui-Hirai H, Iguchi A.
    • Journal Title

      J Am Geriatric Soc (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Risks of CHD identified by different criteria of metabolic snydrome and related changes of adipocytokines in elderly post menopausal women.2007

    • Author(s)
      Ding Qunfang, Hayashi T, Matsui-Hirai H, Packiasamy AR, Iguchi A et al.
    • Journal Title

      J Diabetes and its Complication (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nitric oxide (NO) is a new clinical biomarker of survival in the elderly patients and its efficacy might be nearly equal to albumin.2007

    • Author(s)
      Osawa M, Hayashi T, Nomura H, Funami J, Miyazaki A, Ignarro LJ, Iguchi A.
    • Journal Title

      Nitric Oxide 16

      Pages: 157-163

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 17beta-estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase by High Glucose : Relevance to Postmenopausal Diabetic Cardiovascular Disease.2007

    • Author(s)
      Miyazaki-Akita A, Hayashi T, Ding QF, Shiraishi H, Nomura T, Hattori Y, Iguchi A.
    • Journal Title

      J Pharmacol Exp Ther 320

      Pages: 591-598

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] b1 antagonist and b2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFa in rat with type II diabetes.2007

    • Author(s)
      Hayashi T, Packiasamy ARJ, Miyazaki-Akita A, Funami J, Matsui-Hirai H, Fukatsu A, Iguchi A.
    • Journal Title

      Life Science 80

      Pages: 592-599

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] High glucose downregulates the number of caveolae in monocytes through oxidative stress from NADPH oxidase : Implications for atherosclerosis2007

    • Author(s)
      Hayashi T, Juliet PA, Miyazaki A, Ignarro LJ, Iguchi A.
    • Journal Title

      Biochim Biophys Acta 1772

      Pages: 364-372

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nitric oxide (NO) metabolites are associated with survival in older patients-comparison of its efficacy with established markers2007

    • Author(s)
      Hayashi T, Nomura H, Osawa M, Miyazaki A, Funami J, Matsui-Hirai H, Iguchi A.
    • Journal Title

      J Am Geriatric Soc (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] b1 antagonist and b2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFα in rat with type II diabetes.2007

    • Author(s)
      Hayashi T, Packiasamy ARJ, Miyazaki-Akita A, Funami J, Matsui-Hirai H, Fukatsu A, Iguchi A
    • Journal Title

      Life Science 80

      Pages: 592-599

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nitric oxide (NO) metabolites are associated with survival in older patients-comparison of its efficacy with established markers.2007

    • Author(s)
      Hayashi T, Nomura H, Osawa M, Miyazaki A, Funami J, Matsui-Hirai H, Iguchi A
    • Journal Title

      J Am Geriatric Soc (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Selective iNOS inhibitor, ONO1714 successfully retards the development of high-cholesterol diet induced atherosclerosis by novel mechanism2006

    • Author(s)
      Hayashi T, Matsui-Hirai H, Packiasamy AR, Kano-Hayashi H, Iguchi A.他2名
    • Journal Title

      Atherosclerosis 187

      Pages: 316-324

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Modulating role of estradiol on arginase II expression in hyper-lipidemic rabbits as an atheroprotective mechanism2006

    • Author(s)
      Hayashi T, Esaki T, Sumi D, Mukherjee T, Iguchi A, Chaudhuri G
    • Journal Title

      Proc Natl Acad Sci USA 103

      Pages: 10485-10490

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endothelial Cellular Senescence is Inhibited by Nitric Oxide-Implications in Atherosclerosis Associated with Menopause and Diabetes.2006

    • Author(s)
      Hayashi T, Matsui-Hirai H, Miyazaki-Akita A, Fukatsu A, Funami J, Ding QF, Kamalanathan S, Hattori Y, Ignarro LJ, Iguchi A
    • Journal Title

      Proc Natl Acad Sci USA. 103

      Pages: 17018-17023

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective iNOS inhibitor, ONO1714 successfully retards the development of high-cholesterol diet induced atherosclerosis by novel mechanism.2006

    • Author(s)
      Hayashi T, Matsui-Hirai H, Packiasamy AR, Kano-Hayashi H, Iguchi A et al.
    • Journal Title

      Atherosclerosis 187

      Pages: 316-324

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Modulating role of estradiol on arginase H, expression in hyper-lipidemic rabbits as an atheroprotective mechanism.2006

    • Author(s)
      Hayashi T, Esaki T, Sumi D, Mukherjee T, Iguchi A, Chaudhuri G.
    • Journal Title

      Proc Natl Acad Sci U S A 103

      Pages: 10485-10490

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endothelial Cellular Senescence is Inhibited by Nitric Oxide -Implications in Atherosclerosis Associated with Menopause and Diabetes.2006

    • Author(s)
      Hayashi T, Matsui-Hirai H, Miyazaki-Akita A, Fukatsu A, Funami J, Ding QF, Kamalanathan S, Hattori Y, Ignarro LJ, Iguchi A.
    • Journal Title

      Proc Natl Acad Sci U S A 103

      Pages: 17018-17023

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Modulating role of estradiol on arginase II expression in hyper-lipidemic rabbits as an atheroprotective mechanism2006

    • Author(s)
      Hayashi T, Esaki T, Sumi D, Mukherjee T, Iguchi A, Chaudhuri G
    • Journal Title

      Proc Natl Acad Sci U S A 103

      Pages: 10485-10490

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Endothelial Cellular Senescence is Inhibited by Nitric Oxide -Implications in Atherosclerosis Associated with Menopause and Diabetes.2006

    • Author(s)
      Hayashi T, Matsui-Hirai H, Miyazaki-Akita A, Fukatsu A, Funami J, Ding QF, Kamalanathan S, Hattori Y, Ignarro LJ, Iguchi A.
    • Journal Title

      Proc Natl Acad Sci U S A. 103

      Pages: 17018-17023

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 1-Citiulline and 1-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits.2005

    • Author(s)
      Hayashi T, Packiasamy AR, Matsui-Hirai H, Miyaxaki A, Ignarro Lj, Iguchi A.他2名
    • Journal Title

      Proc Natl Acad Sci U S A 102巻38号

      Pages: 13681-13686

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The treadmill exercise-tolerance test is useful for the prediction and prevention of ischemic coronary events in elderly diabetics2005

    • Author(s)
      Hayashi T, Nomura H, Esaki T, Hattori A, Kano-Hayashi H, Iguchi A
    • Journal Title

      J Diabetes and its Complication 19巻5号

      Pages: 264-268

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NADPH Oxidase Inhibitor, Apocynin, restores the impaired endothelial dependent and independent responses and scavenges superoxide anion in Rats with Type II Diabetes2005

    • Author(s)
      Hayashi T, Packiasamy AR, Kano-Hayashi H, Tsunekawa T, Iguchi A.他2名
    • Journal Title

      Diabetes, Obesity and Metabolism 7巻4号

      Pages: 334-343

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bowel incontinence is related to improvement in basic activities of daily living (BADL) in residents of long-term care health facilities for the elderly in Japan2005

    • Author(s)
      Nomura H, Hayashi H, Hayashi T., Endo H, Miura H, Satake S, Iguchi A
    • Journal Title

      Geriatrics Gerontology International 5巻1号

      Pages: 48-52

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 2,4,6-Trinitrotoluene inhibits endothelial nitric oxide synthase activity and elevates blood pressure in rats.2005

    • Author(s)
      Sun Y, Miyauchi T, Sumi D, Hayashi T, Shimojo N, Kumagai Y. 他4名
    • Journal Title

      Arch Toxicol 79巻12号

      Pages: 705-710

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The effect of high glucose on NO and superoxide anion through endothelial GTPCH1 and NADPH oxidase2004

    • Author(s)
      Ding Qunfang, Toshio Hayashi, Packiasamy AR Juliet, Akihisa Iguchi他5名
    • Journal Title

      Life Sciences 75巻・4号

      Pages: 3185-3194

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Strategy for treating elderly Japanese with hypercholesterolemia2004

    • Author(s)
      Horiuchi H, Matsuzawa Y, Hayashi T, Yamane K, Egusa G, Kita T他11名
    • Journal Title

      Geriatrics Gerontology International 4巻・2号

      Pages: 151-157

    • NAID

      10014317066

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A new HMG-CoA reductase inhibitor, pitavastatin remarkably retards the progression of high cholesterol induced atherosclerosis in rabbits.2004

    • Author(s)
      Hayashi T, Rani P JA, Fukatsu A, Matsui-Hirai H, Osawa M他3名
    • Journal Title

      Atherosclerosis 176巻4号

      Pages: 255-263

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Risks of CHD identified by different criteria of metabolic snydrome and related changes of adipocytokines in elderly post menopausal women

    • Author(s)
      Ding Qunfang, Hayashi T, Matsui-Hirai H, Packiasamy AR, Iguchi A.他2名
    • Journal Title

      J Diabetes and its Complication 印刷中

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Selective iNOS inhibitor, ONO1714 successfully retards the development of high-cholesterol diet induced atherosclerosis by novel mechanism.

    • Author(s)
      Hayashi T, Matsui-Hirai H, Packiasamy AR, Kano-Hayashi H, Iguchi A.他2名
    • Journal Title

      Atherosclerosis 印刷中

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The treadmill exercise-tolerance test is useful for the prediction and prevention of ischemic coronary events in elderly diabetics

    • Author(s)
      Hayashi T, Nomura H, Esaki T, Hattori A, Kano-Hayashi H, Iguchi A.
    • Journal Title

      J Diabetes and its complication 印刷中

    • Related Report
      2004 Annual Research Report
  • [Journal Article] NADPH Oxidase Inhibitor, Apocynin, restores the impaired endothelial dependent and independent responses and scavenges superoxide anion in Rats with Type II Diabetes

    • Author(s)
      Hayashi T, Packiasamy AR, Kano-Hayashi H, Tsunekawa T, Iguchi A.他2名
    • Journal Title

      Diabetes, Obesity and Metabolism 印刷中

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Bowel incontinence is related to improvement in basic activities of daily living (BADL) in residents of long-term care health facilities for the elderly in Japan

    • Author(s)
      Nomura H, Hayashi H, Hayashi T., Endo H, Miura H, Satake S, Iguchi A
    • Journal Title

      Geriatrics Gerontology International 印刷中

    • Related Report
      2004 Annual Research Report
  • [Book] 酸化ストレスと心血管病(執筆項目 酸化ストレスとエストロゲン)2007

    • Author(s)
      横山 光宏, 藤田 敏郎 編集, 林 登志雄, 井口昭久 著
    • Total Pages
      386
    • Publisher
      日本医学出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Book] Oxidative Stress and Cardiovascular Disease2007

    • Author(s)
      Mitshiro Yokoyama, Toshiro Fujita (ed.)Toshio Hayashi, Akihisa Iguchi(auth.)
    • Total Pages
      386
    • Publisher
      Nihon Igaku Shuppan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 改訂高齢女性の健康増進のためのホルモン補充療法ガイドライン(編集 大内尉義)2004

    • Author(s)
      林 登志雄他8名
    • Total Pages
      388
    • Publisher
      メジカルビュー社
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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