Kazuya Tanase

Modulation of Stretch Evoked Adenosine Triphosphate Release From Bladder Epithelium by Prostaglandin E2

PURPOSE We previously reported that cyclooxygenase inhibitors improved storage function in rats with detrusor overactivity caused by cerebral infarction via C-fiber suppression but the precise mechanism underlying this effect remained unclear. In this study we investigated the effects of cyclooxygenase inhibitors on stretch evoked adenosine triphosphate and prostaglandin E(2) release from bladder epithelium. MATERIALS AND METHODS Whole bladders excised from normal rats were fixed vertically in an organ bath filled with Krebs solution. Bladders were infused with 0.3 ml Krebs solution (baseline), followed by 0.9 ml vehicle or 1.5 ml vehicle/drug solution, or 0.3 ml protamine sulfate (Wako Pure Chemical Industries, Osaka, Japan), followed by 0.3 ml prostaglandin E(2) (Nacalai Tesque, Kyoto, Japan). Solutions were allowed to stand for 10 minutes and collected. Adenosine triphosphate and prostaglandin E(2) concentrations were measured by luciferin-luciferase assay and enzyme-linked immunoassay, respectively. RESULTS Adenosine triphosphate and prostaglandin E(2) release from bladder epithelium was increased by distention in volume dependent fashion. A 100 μM dose of the nonselective cyclooxygenase inhibitors FYO-750, ketoprofen and indomethacin significantly suppressed the increased adenosine triphosphate and prostaglandin E(2) release. Inhibition of adenosine triphosphate release by 100 μM FYO-750 and indomethacin was antagonized by prostaglandin E(2) co-injection. Prostaglandin E(2) increased adenosine triphosphate release in a nondistending condition, and the 1 μM of the selective EP1 and EP3 receptor antagonists ONO-8711 and ONO-AE5-599, respectively, significantly suppressed the increased adenosine triphosphate release. CONCLUSIONS Results indicate that cyclooxygenase inhibitors suppress adenosine triphosphate release from bladder epithelium via decreasing prostaglandin E(2). EP1 and/or EP3 receptors appear to participate in this effect.

Endovascular Treatment for an Iliac Artery–Ureteral Fistula with a Covered Stent

Iliac artery-ureteral fistula (IAUF) is a rare entity that has a potential risk of life-threatening hemorrhage. It is difficult to diagnose and treat appropriately. Conventional treatment for the disease consists of surgical ligation and vascular reconstruction or coil embolization. Surgical treatment is usually difficult for patients with several risk factors. In recent years, endovascular stent-graft treatment for iliac artery pseudoaneurysm has been reported. The present report describes two cases in which endovascular covered stent-graft treatment was successfully applied to treat IAUF, with good clinical outcomes.

Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats

PURPOSE The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity. METHODS Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after CI or SO, and investigated the effects on cystometrography of i.v. DON. RESULTS Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P < 0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P < 0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P < 0.05). In decerebrated rats, low dose of DON did not change micturition parameters. CONCLUSIONS These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction.

Rare Causes of Hematuria Associated with Various Vascular Diseases Involving the Upper Urinary Tract

Hematuria is a commonly encountered symptom of a wide spectrum of diseases, including calculi, tumors, and vascular abnormalities. In rare cases, hematuria is caused by life-threatening vascular diseases. When hematuria is encountered, physicians sometimes fail to include vascular diseases in the differential diagnosis because of their rare association with hematuria. Likewise, radiologists often fail to do so because of the low frequency of occurrence of these diseases. Multidetector computed tomography performed with the bolus injection technique should be the first-line diagnostic test when vascular disease is suspected. Radiologists should be familiar with the various imaging findings of hematuria caused by vascular disease. They should also be familiar with the management options (including endovascular techniques) for hematuria caused by vascular disease, since in some cases affected patients can be treated with interventional procedures.

Improvement in Neurogenic Detrusor Overactivity by Peripheral C Fiber's Suppression With Cyclooxygenase Inhibitors

PURPOSE Cyclooxygenase inhibitors decrease micturition frequency in animals with bladder inflammation but to our knowledge the influence of cyclooxygenase inhibitors on detrusor overactivity has not been investigated. We evaluated the effects, and the site and mechanism of action of cyclooxygenase inhibitors on detrusor overactivity induced by cerebral infarction. MATERIALS AND METHODS Cerebral infarcted rats underwent cumulative intravenous administration of the selective cyclooxygenase-1 inhibitor SC-560 (Sigma), the selective cyclooxygenase-2 inhibitor rofecoxib (Kemprotec, Middlesbrough, United Kingdom) or the nonselective cyclooxygenase inhibitor FYO-750 hourly plus a single intravenous administration of SC-560, rofecoxib or SC-560 plus rofecoxib. To evaluate the site of action cerebral infarcted rats underwent single intracerebroventricular or intrathecal administration of FYO-750. To evaluate the mechanism of action FYO-750 was intravenously administered in diuretic rats or cerebral infarcted rats pretreated with resiniferatoxin. RESULTS For cumulative administration SC-560 (0.3 mg/kg), rofecoxib (0.3 mg/kg) and FYO-750 (0.1 to 1 mg/kg) significantly increased bladder capacity. For single administration neither SC-560 (0.03 mg/kg) nor rofecoxib (0.03 mg/kg) affected bladder capacity but SC-560 plus rofecoxib significantly increased bladder capacity vs vehicle. Intracerebroventricular and intrathecal administration of FYO-750 did not affect bladder capacity. FYO-750 did not affect urinary production in diuretic rats and the effects of FYO-750 were blocked by resiniferatoxin except at the highest drug dose. CONCLUSIONS Results indicate that cyclooxygenase inhibitors improve detrusor overactivity caused by cerebral infarction by suppressing peripheral C fibers without affecting urinary production. The nonselective cyclooxygenase inhibitor showed more potent efficiency than the selective cyclooxygenase-1 or the cyclooxygenase-2 inhibitor alone.

Antidiuretic effect of antimuscarinic agents in rat model depends on C‐fibre afferent nerves in the bladder

Antichollnergic agents are anticipated to diminish storage symptoms, as well as nocturia. Nevertheless, the effect of this treatment on polyuria related to nocturia is not clear. By subgroup analysis of the data set from a phase III clinical trial of antimuscarinic agent for OAB patients in Japan, imidafenacin was found to improve nocturia with a reduction in nocturnal polyuria. This study adds the effects and underlying mechanism of antimuscarinic agents decreasing urine production through inhibition of C‐fibre in the bladder of water‐leaded rats.

NEPHROGENIC ADENOMA IN A PATIENT WITH TRANSITIONAL CELL CARCINOMA OF THE BLADDER RECEIVING INTRAVESICAL BACILLUS CALMETTE-GUERIN

A 76‐year‐old‐man was admitted to our hospital for a recurrent bladder tumor. He had received intravesical bacillus Calmette‐Guérin (BCG) treatment for a transitional cell carcinoma of the bladder. A follow‐up cystoscopy revealed a solitary papillary tumor in the left bladder wall. A transurethral cold cup biopsy revealed a nephrogenic adenoma without any evidence of malignant cells. We discuss the pathogenesis of nephrogenic adenoma and suggest that prolonged cystitis caused by intravesical BCG may play an etiological role.

Urethral Sensations are Related to the Development of Detrusor Overactivity

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C‐fiber afferent nerves. α1A‐adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A‐adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.

Co-administration of an α1-blocker improves the efficacy and safety of antimuscarinic agents in rats with detrusor overactivity

Objective:  To investigate the efficacy and safety of a combination treatment with α1‐blockers and antimuscarinics for detrusor overactivity in rats.

CYCLOOXYGENASE INHIBITORS IMPROVE NONINFLAMMATORY OVERACTIVE BLADDER CAUSED BY CEREBRAL INFARCTION BECAUSE OF SUPPRESSION OF PERIPHERAL C-FIBER

is unclear. This study aims to investigate the direct effects of BoNT/A on sensory afferent firing in an ex vivo mouse bladder preparation. METHODS: Adult male mice were sacrificed humanely according to UK legislation. The whole pelvic region was dissected out and placed in a recording chamber superfused with oxygenated Krebs-bicarbonate solution (95% O2, 5% CO2) at 35°C. The urethra and dome were catheterised. Recording of afferent nerve firing was performed by placing a pelvic sensory nerve bundle into a suction electrode, as previously described (Daly et al, 2007). This preparation enabled simultaneous sampling of intravesical pressure and multiunit afferent nerve firing. Ramp distension (100μl.min-1) of the bladder with saline (NaCl, 0.9%) up to 40 mmHg was repeated at 10 minute intervals. To determine the effect of BoNT/A, 2U (BOTOX®) was applied to the bladder lumen during distension, preceded and followed by the control (saline) distension protocol. The effects of BoNT/A was monitored for over 2 hours post application. Data are presented as normalised to the response prior to application of BoNT/A and presented as mean ± S.E.M. Statistical analysis was carried out using either a 2-way ANOVA followed by a Bonferroni post test or paired Students t-test. RESULTS: Ramp distension of the bladder evoked a graded increase in afferent firing with increasing intravesical pressure, which was reproducible following repeated distensions with saline. Following addition of BoNT/A, the afferent response was significantly attenuated after 1 hour. At 2 hours, the maximum afferent firing at 40 mmHg was reduced by 75.9 ± 12.2% (control: 116 ± 13.6 vs. BoNT/A: 24.1 ± 12.2, P=0.0016, n=5). A 2-way ANOVA revealed statistically different afferent responses > 15 mmHg. Interestingly, bladder compliance was not affected after application of BoNT/A (P=0.38). CONCLUSIONS: These results indicate that intravesical BoNT/A directly attenuated distension evoked sensory afferent nerve firing in vitro. BoNT/A application did not affect bladder compliance. Further studies are required to determine how BoNT/A affects mechano-sensory pathways in the bladder. Daly D et al. J Physiol 2007 Sep;583(2):663-674