尿道結石與膀胱過動症治療策略與研究的發展

Abstract

過多的氧化壓力在許多泌尿科學方面的疾病愈症狀扮演著重要的腳色，例如泌尿系統癌症、尿路結石、不孕、性功能障礙、慢性腎臟病變、膀胱過動症、與其他下泌尿路排尿障礙等疾病。 在過去的臨床與基礎研究可發現，尿路結石與氧化壓力的產生可能互為因果，且尿路結石在產生與排除的過程中有可造成泌尿道的損傷，導致體外震波碎石的治療效果降低；許多臨床文獻利用無顯影劑輔助之電腦斷層來判斷患者的腰側疼痛是否為尿路結石所引起之腎絞痛，也利用結石在電腦斷層上的特性來判斷輸尿管結石是否能成功以體外震波碎石治療，但電腦斷層並非判斷病人是否罹患尿路結石疾病的必要臨床影像工具，且對於體外震波碎石也無法在術中提供即時定位的功能，另外在台灣健保審核結石疾病之給付時也並非必要之檢查項目，故目前許多文獻利用結石於電腦斷層上的特徵來做為手術成功與失敗的預測因子，無法完整應用於實際臨床上的判斷，故本論文之第一個研究部分，利用生物統計方法找出無電腦斷層輔助之體外震波碎石手術成功的預測因子，期待結果能增進體外震波碎石手術之成功率，我們並進一步利用測定結石患者尿液的氧化壓力，比較是否較一般人為高。 對苯二胺為頭髮染劑與皮革染劑之常見的成分，對苯二胺與其具有毒性的代謝物能夠產生過量的過氧化物，而在過去的臨床與動物實驗文獻中已證明了於膀胱內若由於各種疾病引起過度的氧化壓力，將會導致組織的受損與膀胱的失能，因此我們於本論文的第二個基礎研究部分，將嘗試長期給予老鼠低劑量的對苯二胺，觀察膀胱受損的狀況，然後進一步應用合成的擬含鎳超氧化物歧化酶治療對苯二胺引起之膀胱失能。The excessive reactive oxygen species (ROS) play an important part in development of urological diseases or conditions, such as cancer, urolithiasis, infertility, sexual dysfunction, chronic kidney disease, overactive bladder, and other lower urinary tract symptoms.

Among previous clinical and basic researches, urolithiasis and oxidative stress interact as both cause and effect. Generation and passing of urolithiasis might cause urinary tract injuries, which might decrease efficacy of extracorporeal shock wave lithotripsy (ESWL). The existent studies explored the utility of Non-contrast computed tomography (NCCT) on diagnosis of urolithiasis and defining predictors of successful ESWL. However, NCCT is not always performed clinically if the diagnosis of ureteral calculi has been confirmed by other radiographics. NCCT is of no help for real-time localization of calculi. NCCT is also unnecessary prior to ESWL for National Taiwan Health Insurance medical claims reviews. Thus, there is a discrepancy between the accumulated evidence of predictors based on NCCT and those available in clinical practice. The first clinical study was to find biometrical predictors for the success of ESWL without assistance of NCCT. The results would enhance the clinical decision making and successful rates of stone clearance. Furthermore, we define existence of the free radicals in urine with electron paramagneic resonance.

Para-phenylenediamine (PPD) is a common ingredient in hair and leather dyes. PPD and its toxic metabolites induce excess reactive oxygen species formation. Oxidative stress from varies etiology upregulates tissue-damage marker compounds and induces bladder dysfunction in clinical and animal studies. We hypothesized chronic PPD exposure results in bladder injuries. Furthermore, we evaluated the therapeutic effect of synthetic nickel-containing superoxide dismutase mimics on PPD-induced bladder dysfunction rat models.