2015 Fiscal Year Annual Research Report
血管内皮増殖因子ＶＥＧＦ系を基軸とする、敗血症性多臓器不全の治療戦略の研究
| Project/Area Number |
25462812
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 医学 / 外科系臨床医学 / 救急医学 / 集中治療学 / 敗血症 |
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| Outline of Annual Research Achievements |
We completed three years of current project. In these three years of project, we used various pharmacological interventions for the treatment of multiple organ dysfunction syndrome (MODS) from early sepsis, some drugs like endothelin blockade, TNF-alpha blockade, protease activated receptor 2 (PAR2) blockade, VEGF receptor antagonist, ultra-short acting beta blocker as therapeutics for MODS in sepsis. Over last several years including the current project we found that endothelin-1 and VEGF play important roles in the pathogenesis of MODS in sepsis with an organ specific roles. In last year of project, we found beta blocker like landiolol has potential roles in reversing sepsis mediated brain and renal injury through the modulation of VEGF and endothelin system. An addition we found landiolol treatment actively arrests acute lung injury in sepsis through suppression of upregulated endothelin system. We also did primary culture of alveolar macrophage and found landiolol inhibited the LPS-induced endothelin upregulation in alveolar macrophage. In another set of experiments, we found diabetes is a strong risk factor for the worsening of MODS in sepsis. Roles of VEGF in MODS became more evident when DM co-existed with sepsis. The downregulation of VEGF in pulmonary and cardiac tissues becomes more prominent when DM is co-existed with sepsis. We also performed clinical research on sepsis with Hokkaido University. We found a potential role of activated protein kinase C in pathogenesis of sepsis with the alteration in VEGF in Japanese sepsis patients.
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Research Products
(8 results)
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[Journal Article] Hyperinflation deteriorates arterial oxygenation and lung injury in a rabbit model of ARDS with repeated open endotracheal suctioning.2015
Author(s)
J. Kamiyama, S. Jesmin, H. Sakuramoto, N. Shimojo, M.M. Islam, K. Hagiya, M. Sugano, M. Oki, T. Unoki, S. Kawano, T. Mizutani
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Journal Title
BMC Anesthesiology15
Volume: 15(73)
Pages: 1-11
DOI
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Three hours treatment of landiolol hydrochloride, an ultra-short-acting β-blocker, is not effective to reverse altered pulmonary endothelin-1 system in acute lung injury in a rat model of early hours of endotoxemia2015
Author(s)
Yujiro Matsuishi, Subrina Jesmin, Sakuramoto hideaki, Nobutake Shimojo, Shila Akhtar, Sohel Zaedi, Tanzila Khatun, Satoru Kawano, Taro Mizutani
Organizer
The Fourteenth International Conference on Endothelin
Place of Presentation
Savannah, GA, United States of America
Year and Date
2015-09-02 – 2015-09-05
Int'l Joint Research
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[Presentation] Amelioration of acute liver injury with the blockade of protease activated receptor-2 (PAR2) through the suppression of upregulated levels of Endothelin-1 and TNF-α in a rat model of endotoxemia2015
Author(s)
Subrina Jesmin, Sohel Zaedi, Nobutake Shimojo, Shila Akhtar, Md. Arifur Rahman, Yujiro Matsuishi, Naoto Yamaguchi, Sayeeda Nusrat Sultana, Satoshi Gando, Satoshi Sakai, Saturo Kawano, Takashi Miyauchi
Organizer
The Fourteenth International Conference on Endothelin
Place of Presentation
Savannah, GA, United States of America
Year and Date
2015-09-02 – 2015-09-05
Int'l Joint Research
