2006 Fiscal Year Final Research Report Summary
Elucidation of molecular mechanisms and therapeutic strategies for diabetic angiopathic complications
| Project/Area Number |
17591074
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | University of Fukui |
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Principal Investigator |
TSUKAHARA Hirokazu University of Fukui, Faculty of Medical Sciences, Department of Pediatrics, Lecturer, 医学部附属病院, 講師 (90207340)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Angiopathic complications / Oxidative stress / Nitrative stress / Biological markers / Inflammatory responses / Antioxidants |
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| Research Abstract |
Angiopathy is a major chronic complication of diabetic mellitus and an important cause of increased morbidity and mortality among the patients with diabetes. Possible mechanisms of untoward effects of hyperglycemia include high oxidative stress status. Loads of reactive oxygen species (ROS) that overburden antioxidant systems induce oxidative stress in the body. Major cellular targets of ROS are membrane lipids, proteins, nucleic acids, and carbohydrates. Other investigators and I have introduced specific biomarkers for oxidative damages and antioxidant defenses into the field of pediatric medicine. Specifically, I have presented age-related reference normal ranges of oxidative stress biomarkers, including urinary acrolein-lysine, 8-hydroxy-2'-deoxyguanosine, nitrite/nitrate, and pentosidine, and the changes of the parameters in diabetes mellitus. I have also presented the data indicating that expression of both adhesion molecules and chemokines in human microvascular endothelial cells induced by inflammatory cytokine TNF-α is inhibited significantly by pretreatment with antioxidants or NO donors, possibly in part through blocking the activation of NF-κB. These experimental results suggest a potential therapeutic approach using antioxidants or NO donors in the treatment of oxidative stress related inflammatory diseases. These informations will be helpful to understand the pathogenesis and management of diabetic angiopathy, including atherosclerosis, retinopathy and nephropathy.
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