University of the Ryukyus · Faculty of Medicine · 助教

Research keywordsbladder dysfunction・male infertility・seminiferous tubules・urodynamic models・stress urinary incontinence・FGFR3 fusion・andropause

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• Time-dependent bladder activity changes in streptozotocin-induced female diabetic rats2025 · Izumi, K; Kamijo, TC; Oshiro, T; Kimura, R; Ashikari, A; Kurobe, M; Akimoto, T; Miyazato, M
• Adenosine Receptor Mechanisms Underlying Bladder Dysfunction in Male Rats With Bladder Outlet Obstruction2025 · <h4>Aims</h4>We examined the role of subtypes of adenosine receptors in bladder dysfunction and changes in the adenosine receptor expression in the bladder using male rats with partial bladder outlet obstruction (BOO).<h4>Methods</h4>In Sprague-Dawley rats (male 8-weeks old), BOO was produced by a partial ligation of the urethra along a metal rod of a 1.2 mm outer diameter. Control rats underwent sham operation. Awake cystometrograms (CMG) were first recorded during saline instillation, and then an adenosine A1 receptor agonist (CCPA, 4.1 μM), an adenosine A2A antagonist (ZM241385, 15 μM), or inosine (1 mM) were applied intravesically in sham and BOO rats. In addition, mRNA levels of adenosine receptor subtypes in the bladder wall were measured using RT-PCR. Histological studies of bladder specimen were also performed.<h4>Results</h4>Weights of BOO bladders were significantly (p < 0.0001) larger compared with sham bladders. In CMG, a number of non-voiding contractions (NVCs), bladder contraction amplitudes during voiding, bladder capacity, and post-void residual (PVR) were significantly (p < 0.001) increased compared with sham rats. Voiding efficiency (VE) was significantly (p < 0.001) reduced in BOO versus sham rats. Intravesical application of CCPA or inosine did not induce statistically significant effects on CMG parameters in BOO rats. Yet, ZM241385 induced a significant (p = 0.040) reduction in NVCs of BOO rats. mRNA levels of adenosine A2A and A3 receptors were significantly (p < 0.0001 and p = 0.0145, respectively) upregulated in the BOO bladder mucosa, whereas adenosine A2B receptors showed a significant (p < 0.0001) reduction in the BOO bladder mucosa compared with sham bladders. Histologically, we found the thickened detrusor muscle layer in BOO versus sham rats.<h4>Conclusions</h4>The male rat model of BOO seems to be suitable for exploring urethral obstruction-related bladder dysfunction at the compensated phase. In addition, the adenosine A2A receptor subtype would be a potential target for the treatment of male BOO patients with bladder overactivity.<h4>Clinical trial registration</h4>A clinical trial registration is not required as this study reported the basic research data using animal models.
• 精漿中の金属成分に関する生化学的研究の動向2024 · 古城 公佑, 田中 隆造, 小栗 朋子, 中園 亜由美, 清水 拓弥, 藤本 俊介, 沼畑 大介, 黒部 匡広, 柿沼 敏行, 内田 将央, 山崎 一恭, 池田 篤史, 高山 達也, 根来 宏光, 西山 博之
• Feasibility of high-frequency ultrasound for seminiferous tubule assessment and correlation of B-mode imaging with pathological findings in the testis in azoospermia2024 · PURPOSE: To determine the feasibility of high-frequency ultrasound (HFUS) for assessing seminiferous tubules and to understand high-resolution B-mode images of the testes in cases of azoospermia. METHODS: We verified how the histopathological images of testicular biopsy specimens can be observed using HFUS images and measurement analysis of seminiferous tubules was performed to 28 testes of 14 cases with azoospermia who underwent preoperative ultrasound and microdissection testicular sperm extraction (micro-TESE). The population consisted of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), including Sertoli cell-only syndrome (SCOS), and the other pathologies. Statistical verification of differences in seminiferous tubule diameters among preoperative ultrasound examination, ultrasound examination of pathological specimens, and histopathological specimens. We also examined the imagingpathology correlation via a case series presentation, aiming to identify imaging markers of testicular pathology and determine the possibility of predicting each condition. RESULTS: A comparison between HFUS images and histopathology from the same biopsy specimens suggested that ultrasonography could be seen as stereoscopic images due to its significantly greater slice thickness. The diameters of tubules were generally larger in pathological tissues as compared to ultrasonographic findings in OA and SCOS, but not in the other conditions. Comparisons provided insights into the predictability of SCOS and revealed imaging findings such as gaps between tubules and decreased diameter reflective of testicular damage. CONCLUSION: Seminiferous tubules can be observed however the diameter of seminiferous tubules varies in imaging and histopathology depending on the pathology. Imaging findings that reflect testicular damage and the predictability of SCOS were revealed in this study, but further verification is required.

• 尿道のセロトニン陽性パラニューロンに着目した、腹圧性尿失禁の病態解明と治療法探索2021 · 腹圧性尿失禁は高頻度でQOLの低下に直結する重要な疾患であるが、十分なエビデンスを有する治療薬が存在せず、病態のさらなる解明、新規治療薬開発は喫緊の課題である。尿道には腺細胞と神経細胞に共通する特性を持つ一群の内分泌・受容器細胞であるパラニューロン細胞が存在し、その中でセロトニン分泌能を持つものが尿道の機械的、化学的刺激の受容体として機能していると推定されている。一方で尿道組織に存在するセロトニン受容体は尿道の収縮反応への関与が推定されているものの、依然として不明な点が多い。本研究では、尿道でのセロトニン陽性パラニューロンとセロトニン受容体を介したシグナル経路の活性化が尿道収縮の増強に重要な役割を果たしている、という仮説を立て、複数の腹圧性尿失禁病態モデルラットを用いた病態解明と、新規治療法の開発を目的とする。学術的な問いは「尿道でのセロトニン陽性パラニューロンとセロトニン受容体を介したシグナル経路の活性化は腹圧性尿失禁の改善に寄与するのか」という点である。初年度では動物実験モデル作成ならびに膀胱機能測定環境、RT-PCRの準備をすすめた。2つの腹圧性尿失禁病態モデルラット、両側卵巣摘除(ovariectomy;OVX)モデルラットと膣バルーン拡張(vaginal distention;VD)モデルラットの作成に成功した。次年度では尿道基線圧の低下、尿道禁制反射圧の低下などの、腹圧性尿失禁病態モデルとしての表現型の再現性を確認する。さらに摘出した尿道組織を用いたRT-PCRによる発現分子解析や、蛍光免疫染色法を用いたセロトニン陽性パラニューロンの密度変化の解析を進めていく予定である。
• 尿道上皮内セロトニン陽性パラニューロン経路の網羅的解析による腹圧性尿失禁の克服
• 尿路変向による廃用性低活動萎縮膀胱ラットモデルの回復における神経支配の影響の解明

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