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Chronopharmacological study on the diurnal rhythms in bone metabolism.

Research Project

Project/Area Number 02454422
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionTohoku university

Principal Investigator

SHINODA Hisashi  Dept. of pharmacology, Tohoku univ. Sch. of dentistry, Professor, 歯学部, 教授 (80014025)

Co-Investigator(Kenkyū-buntansha) HIRAFUJI Masahiko  Dept. of pharmacology, Tohoku univ. Sch. of dentistry, Instructor, 歯学部, 助手 (20142987)
ONODERA Kenji  Dept. of pharmacology, Tohoku univ. Sch. of dentistry, Lecturer, 歯学部, 講師 (40133988)
ENDO Yasuo  Dept. of pharmacology, Tohoku univ. Sch. of dentistry, Lecturer, 歯学部, 講師 (50005039)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1990: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordscircadian rhythm / bone resorption / mineralization / bisphosphonates / elcatonin / chronopharmacology / rat / 骨代謝 / サ-カディアンリズム / 骨
Research Abstract

1) Time structure of diurnal rhythms in calcium transfer in and out of bone was determined in rats. Peak deposition of calcium into bone and growing incisor occurred at 2400h, with a nadir at 1200h, while, calcium release from bone was maximal around 1200-1600h and lowest late in the dard period. It was shown that a heat sensitive humoral factor(s) regulates diurnal rhythms in bone resorption in rats and in humans. 2) The effect of the time of drug administration was studied in rats using blockers of bone resorption. It was shown that there is a diurnal rhythm in the susceptibility of rats to elcatonin, sodium salicylate and bisphosphonates, which are known to have hypo calcemic or anti-osteolytic action. It was also shown that the magnitude of hypocalcemic or anti-osteolytic effects of these drugs depend on the phase of diurnal rhythms in bone resorption. The above results suggest that more predictable and efficacious results might be attained if the diurnal rhythmicities in bone metabolism were taken into consideration in designing treatment regimens with blockers of bone resorption.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] H.Shinoda,P.H.Stern: "Diurnal rhythm in endogeneous bone resorbing activity in rat serum." J.Bone Miner.Res.5(Supple2). S129 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda: "Diurnal rhythm in the susceptibility of rats to elcatonin,Cl_2MBP and HEBP" Jpn.J.Pharmacol. 52(Supple1). 312P (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 篠田 壽: "硬組織代謝のサーカディアンリズムと薬効の日内変動" 東北大歯誌. 10. 49 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda,K.Onodera: "Diurnal variation in the hypocalcemic effect of sodium salicylate" Jpn.J.Pharmacol. 55(Supple1). 135P (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda,P.H.Stern: "Diurnal rhythms in Ca transfer into bone,Ca release from bone and bone resorbing activity in serum of rats." Am.J.Physiol. 262. R235-R240 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] P.H.Stern,P.Lakatos,H.Shinoda et al.: "Relation of diurnal rhythm of cortisol to bone-resorbing activity in human serum" Osteoporosis Int.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda, P.H.Stern: "Diurnal rhythm in endogeneous bone resorbing activity in rat serum." J Bone Miner Res.5(Supple.2). S129 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda: "Diurnal variations in the susceptibility of rats to elcatonin, C12MBP and HEBP and their relations to the circadian rhythms in bone metabolism." Jpn J Pharmacol.52(Supple.1). 312 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda, K.Onodera: "Diurnal variation in the hypocalcemic effect of sodium salicylate." Jpn J Pharmacol.55(Supple.1). 135 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda, P.H.Stern: "Diurnal rhythms in Ca transfer into bone, Ca release from bone and bone resorbing activity in serum of rats." Am J Physiol.262. 235-R240 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda: "Diurnal variation in the susceptibility of rats to elcatonin and sodium salicylate." Bone and Miner.17(Supple.1). 333 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] P.Lakatos, A.Blumsohn, R.Eastell, B.Morris, H.Shinoda, P.H.Stern: "Diurnal rhythms of human serum bone resorbing activity." J Bone Miner Res.7(Supple.1). S177 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] P.H.Stern, P.Lakatos, G.Tarjan, A.Blumsohn, R.Eastell, H.Shinoda: "Relation of Diurnal rhythm of cortisol to bone-resorbing activity in human serum." Osteoporosis Int.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.Shinoda,P.H.Stern: "Diurnal rhythms in Ca transfer into bone,Carelease from bone,and bone resorbing activity in serum of rats." American Journal of Physiology. 362. R235-R240 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Shinoda: "Piurnal variations in the susceptibility of rats to elcatonin and sodium salicylate" Bone and Mineral. 17. 333- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] P.Lakatos,H.Shinoda et al.: "Diurnal rhythms of human serum bone resorbing activity" Journal of Bone and Mineral Research. 7. S177- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 篠田 壽: "Bisphosphonatesの骨吸収抑制作用" Japanese Journal of Pharmacology. 58(Supple I). 28P- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 大塚 美重 篠田 壽: "成長期のラット切歯象牙質にみられる成長線の周期性に関する研究:生物リズムの個体発生" 歯科基礎医学会雑誌. 34(秒録号). 146- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hisashi Shinoda: "Diurnal rhythms of Calcium transter into bone,Calcium release from bome and bone resorbing activity in serum of rats." Amer.J.Physiol.in press.

    • Related Report
      1991 Annual Research Report
  • [Publications] A.Togari: "Effect of HEBP on experimental osteoporosis imduced by ovariectomy in rats." Japan J.Pharmacol.56. 177-185 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Hirafuji: "Plateletーleukocyte interaction in adhesion to endothelial cells induced by plateletーactirating factor in vitro." Brit.J.Pharmacol.103. 1333-1338 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Hirafuji: "PAFーmediated platelet adhesion to endothelial cells induced by FMLPーStimulated leukocytes." J.Lipid Mediators. 4. 347-352 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Onodera: "Pharmacological characterisfics of catalepsy induced by intraーcerebroventicular administration of histamine in mice." Agents and actions. 33. 134-146 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hisashi Shinoda: "Diurnal variations in the susceptibility of rats to elcatonin,bisphosphonates and sodium salicylate." Calcit Tiss.Int.

    • Related Report
      1991 Annual Research Report
  • [Publications] Hisashi Shinoda: "Diurnal uariations in the susceptibility of rats to elcatonin,Cl_2MBP,and HEBP and their relations to the circadian rhythms in bone metabolism." The Japanese Journal of Pharmacology. 52. 319 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hisashi Shinoda,Paula H.Stern: "Diurnal rhythms in calcium fransfer into bone,calcium release from bone,and bone resorbing activity in Serum of rats" American Journal of Physiology. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] A.Togari,M.Arai,M.Hironaka,S.Matsumoto,H.Shinoda: "Effect of HEBP(1ーHydroxyethylideneー1,1ーbisphosphonate)on experimental osteoporosis induced by ouariectomy in rats" The Japanese Journal of Pharmacology,. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Onodera,H.Shinoda: "Pharmacological characteristics of catalepsy induced by intracerebroventricular administration of histamine in mice" Agents and Actions. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Hirafuji,H.Shinoda: "Plateletーleukocyte interaction in adhesion to endothelial cells induced by plateletーactivating factor in uitro" British Journal of Pharmacology. (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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