| Co-Investigator(Kenkyū-buntansha) |
HIGASHIDA Kousuke Yamanashi Medical College, Pediatrics Fellow, 医学部, 助手 (60173142)
ASAYAMA Kohtaro Yamanashi Medical College, Pediatrics Fellow, 医学部, 助手 (70129310)
AMEMIYA Shin Yamanashi Medical College, Pediatrics Assistant Professor, 医学部, 講師 (10118903)
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| Research Abstract |
The project aimed to establish the early diagnosis with pathophysiologic and pathochemical indicies of diabetic complications in patients with childhood-onset diabetes mellitus. This project consisted of the two main themes ; one was the pathophysiological aspect of early stage of diabetic nephropathy, and another was the pathochemical aspect of free radicals and lipoprotein metabolisms in the development of diabetic complications.
As to the pathophysiologic characteristics of diabetic nephropathy, we first proved that glomerular hyperfiltration played the major role in the decreasing renal functional the early stages from microalbuminuria through overt proteinuria, which were examined by the low-dose dopamine infusion test. Then the glomerular hyperfiltration was evaluated by the tubuloglomerular feed-back loop, the activation of which leaded to the increased total exchangeable Na content, and tended to accumulate Na before the development of hypertension in diabetic nephropathy. The p
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athophysiologic characteristics depended on the increased urinary Na excresion (FENa) through the change of suppressed circulatory renin-angiotensin system, enhanced renal catecholamine metabolism, and the increment of atrial natriuretic peptide (hANP). This mechanism began to operate even before the microalbuminuric stages started. From the clinical aspect, the indicies can be established with the low active to total renin ratio and the increcased hANP associated with high FENa. These findings indicate that the prevention of diabetic nephropathy can be achieved by the restriction of Na metabolism with restiction of Na intake and/or angiotensin converting enzyme inhibitors, as well as the normalization of blood glucose.
From the pathchemical aspects of free radical and lipoprotein metabolism, we established the highly specific assay systems for lipid peroxides and various antioxidant enzymes in diabetic, starved, and obese animal models. In addition, the immuno-histochemical staining techniqus was investigated and applied to the localization of superoxide dismutase (CuZnSOD in cytoplasma and MnSOD in mitochondria) in various organs. With using these approaches, the role of free radicals was specifically analyzed in the progress of microvascular damages and artherosclerosis in diabetes mellitus. Furthermore, the minute changes of free radicals and lipoprotein metabolism were observed in both insulin-dependent diabetic children, which revealed the back ground abnormalities of early diabetic complications. Less
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