| Project/Area Number |
18390433
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | University of Fukui |
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Principal Investigator |
YOKOYAMA Osamu University of Fukui, Faculty of Medical Sciences, Professor (90242552)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Yoshitaka University of Fukui, Faculty of Medical Sciences, Assistant Professor (30273006)
YOKOTA Yoshifumi University of Fukui, Faculty of Medical Sciences, Professor (50222386)
AKINO Hironobu University of Fukui, Faculty of Medical Sciences, Associate Professor (90159335)
TANASE Kazuya University of Fukui, Hospital, Assistant Professor (00359720)
KUSUKAWA Naoya University of Fukui, Hospital, Medical doctor (80372499)
中井 正治 福井大学, 医学部, 助手 (50372496)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,830,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2007: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2006: ¥11,500,000 (Direct Cost: ¥11,500,000)
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| Keywords | overactive bladder / COX-2 / single nucleotide polymorphism / prostaglandin / BPH / cerebral infarction / spinalcord injure / urinary incontinence |
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| Research Abstract |
It has been reported that a new variant in the COX-2 promoter, a guanine to cytosine substitution at -765 (-765G->C) is located within a putative binding site for the transcription factor Spl. The polymorphism of the COX-2 gene was found to associate with a decreased risk of myocardial infarction and stroke by reduction in PGE2 production. Previously we reported that PGE2 played an important role in neuron-plasticity in the brain and spine, which resulted in the development of OAB. Therefore, in BPH or stroke patients with -765GC genotype or -765CC genotype, development of OAR in believed to be diminished. In the present study, the patients with cerebrovascular accident, spinal lesion, or bladder outlet obstruction (BOO) were classified into two groups ; overactive bladder (OAB) group and non-overactive bladder (non-OAB) group according to the International Prostate symptom Score (IPSS)/OAB symptom score. Blood and urine samples were collected from all patients. Gemonic DNA was prepare
… More
d from blood and -765G->C variant was genotyped by restriction endonuclease digestion of the polymerase chain reaction product. Genotypes were determined. The level of prostaglandin E2 (PGE2) in the urine were analyzed with the severity of OAB. The results obtained in 2006 and 2007 were as follows;
1. The urine levels of PGE2 in patients with BOO were significantly higher than that in control.
2. The urine level of PGE2 in patients with cerebrovascular accident was correlated with severity of IPSS. The patients with high score of IPSS reveals high level of urine PGE2.
3. COX inhibitors dose-dependently inhibited detrusor overactivity caused by cerebral infarction in rats. This effect was dependent on suppression of C-fiver afferent nerves in the bladder.
4. Single nucleotide polymorphism (SNP) in COX-2 promoter gene was found in 3 out of 70 patients with OAB. The results will be presented at 2008 NBS annual meeting in Tokyo. We have to accumulate the samples to analyze the correlation between SNP and severity of OAB.
PGE2 excreted from the urothelium in response to bladder distension stimulates C-fiver afferent nerves, subsequently promoting detrusor overactivity. This mechanism seems to be true in patients with BOO. However, the levels of PGE2 were related with the severity of OAB in patients with cerebrovascular accidents. They were not proven to exist BOO. These results suggest that there might exist other underlying mechanisms to explain the role of PGE2 in OAB. Less
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