Hitoshi Shinbo

Expression and functional role of β-adrenoceptors in the human urinary bladder urothelium

We investigated the presence of β-adrenoceptor subtypes in human urinary bladder urothelium and examined whether β-adrenoceptors in the urothelium modulate the relaxation responses of isolated human detrusor strips to a β-adrenoceptor agonist. Expression of β1-, β2-, and β3-adrenoceptor mRNA in urothelium and detrusor smooth muscle was determined by reverse transcription-polymerase chain reaction, and the distribution of β1-, β2-, and β3-adrenoceptors in human urinary bladder urothelium were examined by immunohistochemistry. Paired human longitudinal detrusor strips with and without an intact urothelium were suspended in organ baths to construct concentration-response curves to isoproterenol. The possible involvement of urothelium-derived nitric oxide (NO) in this response was examined in additional experiments with urothelium-intact strips in the presence of NG-nitro-L-arginine methylester (L-NAME). Results confirmed the expression of β1-, β2-, and β3-adrenoceptors in the human urinary bladder urothelium. Further, the presence of the urothelium caused a parallel rightward shift of the concentration-response curve to isoproterenol with a significant reduction in potency (pEC50). L-NAME failed to exert any significant effect on the relaxation response to isoproterenol in the urothelium-intact strips. These results confirm the presence of β1-, β2-, and β3-adrenoceptors in human urinary bladder urothelium. Further, they suggest that urothelial β-adrenoceptors induce the release of a urothelium-derived factor which inhibits the β-adrenoceptor agonist-induced relaxation of the human detrusor smooth muscle and that this inhibitory mechanism might not involve NO.

Human Muscarinic Receptor Binding Characteristics of Antimuscarinic Agents to Treat Overactive Bladder

PURPOSE We characterized the binding affinities of several antimuscarinic agents in human muscarinic receptors. MATERIALS AND METHODS Competitive inhibitory effects of antimuscarinic agents on specific NMS [H] (PerkinElmer Life Sciences, Boston, Massachusetts) binding were examined in human tissue homogenates and in CHO-K1 cell membranes expressing human muscarinic receptor subtypes. RESULTS Oxybutynin, propiverine, tolterodine, the respective metabolites DEOB, DPr-P-4(N-->O) and 5-HM, and darifenacin inhibited in concentration dependent fashion specific [(3)H]NMS binding in homogenates of the human bladder and parotid gland as well as in membranes of CHO-K1 cell lines expressing human muscarinic M(1) to M(5) receptor subtypes. Based on inhibition constant values the inhibitory effects of tolterodine, 5-HM and DPr-P-4(N-->O) were 1.4 to 1.7 times greater in the bladder than in the parotid gland, whereas the inhibitory effects of oxybutynin, DEOB, propiverine and darifenacin were 2 to 10 times greater in the parotid gland. Consequently tolterodine, 5-HM and DPr-P-4(N-->O) compared with oxybutynin, DEOB, propiverine and darifenacin were found to show 3 to 4 times greater affinity to muscarinic receptors in the human bladder than in the parotid gland. Tolterodine and 5-HM were 2-fold more potent for inhibiting specific [(3)H]NMS binding at cell membranes expressing the M(2) vs the M(3) subtype. Conversely oxybutynin, DEOB, propiverine, DPr-P-4(N-->O) and darifenacin showed 2 to 22 times higher affinity to the M(3) than to the M(2) subtype. CONCLUSIONS Compared with oxybutynin, tolterodine, 5-HM and DPr-P-4(N-->O) may bind more selectively to muscarinic receptors in the human bladder than in the parotid gland.

Effects of a novel β3‐adrenoceptor agonist, AJ‐9677, on relaxation of the detrusor muscle: An in vitro study

Objectives:  To examine the relaxant effects of AJ‐9677, a novel β3‐adrenoceptor agonist, on the isolated rat, monkey and human detrusor muscle.

Seasonal changes in symptom score and uroflowmetry in patients with lower urinary tract symptoms

Objective. To determine whether subjective or objective seasonal changes occur in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Material and methods. A total of 31 patients with LUTS were observed for >5 years. Their International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum flow rate (Qmax), voided volume (VV) and post-void residual (PVR) were measured every month. Results. Total IPSS, QOL, VV or PVR did not show any seasonal changes between the three seasons: summer (hot season: June to September); winter (cold season: December to March); and spring and fall (comfortable season: April, May, October and November). Furthermore, when the IPSS was examined by dividing it into storage symptoms (frequency, urgency and nocturia) and voiding symptoms (incomplete emptying, intermittency, weak stream and straining), no significant seasonal changes were detected. Only Qmax showed a significant seasonal change, being higher in both the cold season (median 10.4 ml/s) and the comfortable season (median 10.1 ml/s) than in the hot season (median 9.4 ml/s). Conclusions. It has generally been thought that LUTS worsen in winter. Our results indicate that the IPSS and the QOL score remain nearly constant if they are determined regularly over an extended period of time. Qmax may however be influenced by seasonal changes in temperature.

Resistive Index: A Newly Identified Predictor of Outcome of Transurethral Prostatectomy in Patients With Benign Prostatic Hyperplasia

OBJECTIVE To examine the usefulness of several preoperative parameters obtained through transrectal ultrasonography in predicting the outcome of transurethral resection of the prostate (TURP). METHODS A total of 572 men aged 51-85 years scheduled to undergo TURP for benign prostatic hyperplasia were prospectively enrolled, and 560 were ultimately evaluated. We preoperatively assessed International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum urinary flow rate (Q(max)), and postvoid residual urine volume (PVR), and measured total prostate volume (TPV), transition zone (TZ) index, and resistive index (RI) using transrectal ultrasonography. To compare the usefulness of the latter 3 indices, we calculated the area under the receiver operating characteristic (ROC) curve for each index and for IPSS. RESULTS IPSS (total, postmicturition symptoms, storage symptoms, voiding symptoms), QOL score, Q(max), and PVR were significantly improved after TURP. Significant differences between the effective and noneffective groups were observed with regard to age, IPSS (total, postmicturition symptoms, storage symptoms, voiding symptoms), QOL score, TPV, TZ index, RI, Q(max), and PVR. The area under the ROC curve was 0.663 for IPSS, 0.691 for TPV, 0.719 for the TZ index, and 0.845 for the RI. CONCLUSIONS The RI is a useful predictor of an effective outcome after TURP in patients with benign prostatic hyperplasia and may be useful for determining suitability for surgical intervention.

Effect of age on the responses of rat bladder detrusor strips to adenosine triphosphate.

Objective To assess age‐related changes in bladder function using the contractile responses to ATP of detrusor strips from rats of various ages.

Expression of β-Adrenoceptor Subtypes in Urothelium, Interstitial Cells and Detrusor of the Human Urinary Bladder

Objective: We examined whether interstitial cells (ICs) of the human urinary bladder expressed β‐adrenoceptor (AR) subtypes, and semiquantitatively compared the staining intensity among urothelium, ICs and detrusor muscles.

Expression and functional role of β3‐adrenoceptors in the human ureter

To investigate the presence of β‐adrenoceptor subtypes in the human ureter, and to examine whether β3‐adrenoceptors modulate relaxation of the human ureter.

Simultaneous bilateral laparoscopic adrenalectomy in ACTH-independent macronodular adrenal hyperplasia

Laparoscopic surgery for urological conditions has now become popular worldwide. The case is reported of a 56‐year‐old woman who underwent simultaneous bilateral laparoscopic adrenalectomy for adrenocorticotropic hormone‐independent macronodular adrenocortical hyperplasia (AIMAH), followed by autotransplantation of resected adrenal gland fragments. Simultaneous laparoscopic adrenalectomies seem feasible for a patient with AIMAH because of its minimally invasive nature. However, autotransplantation of adrenal fragments failed in this patient with AIMAH.

Application of Ultrasonography and the Resistive Index for Evaluating Bladder Outlet Obstruction in Patients with Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is an extremely common and chronic condition that can lead to bladder outlet obstruction (BOO) in elderly men. Although pressure-flow studies are considered the most reliable method for evaluating BOO, they are invasive and complicated. Transrectal ultrasonography (TRUS) is a promising alternative because of its minimal invasiveness. Recently, TRUS imaging has been shown capable of measuring the resistive index, a useful parameter for evaluating BOO and for determining proper medical intervention in patients suffering from BPH.