A small pilot study to evaluate the accuracy and feasibility of a novel automated voiding diary device for recording urine output measurements.

AIMS: Recording a voiding diary can be bothersome for patients and is sometimes inaccurate and unhygienic. This study aimed to develop and assess the accuracy and convenience of a novel device that automatically records the voiding diary by measuring pre- and post-void body weight. METHODS: We used this novel device for seven healthy volunteers and ten hospitalized patients. The examinees got on the device before and after voiding and the device recorded the voiding diary automatically. The examinees also manually recorded a voiding diary by collecting their urine in a cup and measuring its volume and weight. We examined the correlation between the traditional and the automated voiding diary to confirm the accuracy of voiding measurements using this device. Additionally, we investigated which measurement method was preferred by the participants. RESULTS: In the healthy volunteers group, there was a strong correlation between the voided urine weight recorded by the device and voided urine weight measured manually by the examinee (R2 = 0.9935). In the patients group, there was a strong (R2 = 0.9117) but lower correlation than that of the volunteers group, with an error of ±25 g 62% of the time, and ±50 g 82% of the time, respectively. All of the healthy volunteers and seven of the ten patients preferred using the automated voiding diary. CONCLUSIONS: This novel device recorded a reasonably accurate voiding diary for everyday clinical practice.

Pre-treatment serum testosterone level can be a useful factor to predict the improvement in bladder outlet obstruction by tadalafil for male patients with lower urinary tract symptoms induced by benign prostatic obstruction.

INTRODUCTION: To investigate possible pre-treatment factors related to the therapeutic effect of tadalafil on bladder outlet obstruction (BOO). MATERIALS AND METHODS: Eighty untreated outpatients with lower urinary tract symptoms (LUTS) due to BOO received 5 mg tadalafil daily for 12 months. Subjective symptoms and objective findings were evaluated before and 12 months after treatment. At 12 months, the patients were divided into two groups according to an improvement grade in BOO index (BOOI). Patient characteristics including age, serum total testosterone level (TT), PSA, and prostate volume, and subjective and objective parameters on LUTS were set as candidates of pre-treatment factors, and the parameters that influenced the improvement of BOO were statistically analysed. RESULTS: A total of 69 patients with mean age of 69.8 years and mean prostate volume of 48.8 mL were included. Subjective symptoms and BOOI were significantly ameliorated after 12 months. In terms of an improvement of BOOI, 30 patients (43.5%) showed insignificant improvement in BOO, whereas 39 patients (56.5%) exhibited excellent improvement. Comparison of pre-treatment factors between the groups showed that TT was the only independent predictor related to the improvement in BOO. The improvement of BOO was significantly better in patients with higher TT. CONCLUSIONS: Pre-treatment TT was considered to be a useful predictor of therapeutic effects of tadalafil for BOO.

Clinical characteristics and useful signs to differentiate detrusor underactivity from bladder outlet obstruction in men with non-neurogenic lower urinary tract symptoms.

OBJECTIVE: To investigate the clinical characteristics and useful signs to differentiate detrusor underactivity from bladder outlet obstruction in men with non-neurogenic lower urinary tract symptoms. METHODS: A total of 638 treatment-naive men with non-neurogenic lower urinary tract symptoms who underwent subjective and objective evaluations were reviewed retrospectively. We divided the patients into detrusor underactivity and bladder outlet obstruction groups based on urodynamic findings, and compared parameters obtained from questionnaires and non-invasive tests. Detrusor underactivity was defined as bladder contractility index ≤100 and bladder outlet obstruction index ≤40, whereas bladder outlet obstruction was defined as bladder contractility index >100 and bladder outlet obstruction index >40. RESULTS: Of 638 patients, 145 (22.7%) had detrusor underactivity and 273 (42.8%) had bladder outlet obstruction. Total international prostate symptom score and international prostate symptom score-voiding subscore were significantly higher in the detrusor underactivity group. There were significant differences in prostate volume, intravesical prostatic protrusion, and all uroflowmetry parameters between the two groups. In multivariate logistic regression analysis, lower intravesical prostatic protrusion (cut-off value 8.2 mm), lower bladder voiding efficiency (cut-off value 70%), and the presence of sawtooth and interrupted waveform on uroflowmetry were significant predictive factors for detrusor underactivity. In particular, the incidence of sawtooth and interrupted waveform was significantly higher in the detrusor underactivity group (80%) than in the bladder outlet obstruction group (12.8%), which showed both high sensitivity (80%) and specificity (87.2%) in differentiating detrusor underactivity from bladder outlet obstruction. CONCLUSIONS: Sawtooth and interrupted waveform on uroflowmetry can be a useful predictive factor for detrusor underactivity. In addition, lower intravesical prostatic protrusion and bladder voiding efficiency can be of supplementary use.

Analysis of continence reflexes by dynamic urethral pressure recordings in a rat stress urinary incontinence model induced by multiple simulated birth traumas.

The present study evaluated real-time changes in urethral pressure during the storage phase using a rat model with stress urinary incontinence (SUI) induced by simulated multiple birth traumas and investigated the relationship between urethral continence function and dynamic parameters associated with the changes in urethral pressure. Sprague-Dawley rats were divided into the following two groups: the sham group, which underwent three catheterizations of the vagina without distension at 2-wk intervals, and the vaginal distension (VD) group, which underwent three VDs at 2-wk intervals. After transection of the T8-T9 spinal cord, simultaneous bladder and urethral pressure recordings were performed during intravesical pressure elevation. Urodynamic parameters such as leak point pressure (LPP), urethral baseline pressure (UBP), maximum urethral pressure (MUP), the MUP-UBP differential (dUP) during intravesical pressure elevation, the bladder pressure when urethral contraction begins (Puc), and the bladder pressure at bladder neck opening (Pno) were then measured and compared. Compared with the sham group, LPP, UBP, dUP, MUP, Puc, and Pno were significantly decreased in the VD group. Pressure differences between LPP and Pno and between LPP and UBP (LPP-UBP) were also significantly different in the two groups. However, difference values of LPP and MUP or Pno and UBP were not altered after VD. Our new methods of simultaneous recordings of dynamic changes in bladder and urethral pressures are useful to fully evaluate the functional alterations in urethral continence function in the SUI model induced by multiple VDs. Moreover, LPP-UBP values, which correspond to the difference between Valsalva LPP and maximum urethral closure pressure in clinical urodynamics, would be useful to evaluate the impaired urethral continence function after simulated birth traumas in animal models.

Objective impacts of tadalafil on storage and voiding function in male patients with benign prostatic hyperplasia: 1-year outcomes from a prospective urodynamic study.

PURPOSE: To investigate the 1-year effects of tadalafil on storage and voiding function in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (LUTS/BPH) based on a urodynamic study. METHODS: In a one-armed, prospective study, 105 untreated outpatients with LUTS/BPH received 5 mg tadalafil every day for 12 months. Subjective symptoms and objective findings on voiding and storage functions, obtained through urodynamic studies that included cystometry and pressure flow study, were evaluated before, at 3 months, and at 12 months of treatment. RESULTS: The analysis included 94 patients with a mean age of 70.7 years and a mean prostate volume of 44.5 mL. Subjective symptom parameters of LUTS were significantly ameliorated after 3 months, and progressively improved until study conclusion. Similarly, monitoring of storage and voiding functions revealed significant improvements after 3 months that continued to improve until 12 months. In 49 patients who revealed detrusor overactivity during cystometry at the baseline assessment, uninhibited detrusor contractions disappeared in 15 (30.6%) patients after 3 months (p = 0.02), and in 22 (44.9%) after 12 months (p < 0.001). Mean maximum flow rate significantly increased by 2.9 mL/s during the 12-month treatment (p < 0.001), whereas mean bladder outlet obstruction index significantly decreased from 59.5 at baseline to 45.7 at 3 months (p = 0.001), and to 42.9 at 12 months (p < 0.001). CONCLUSIONS: Tadalafil significantly improved storage and voiding functions, along with LUTS, in patients with LUTS/BPH during a 1-year treatment.

Comparison in the efficacy of fesoterodine or mirabegron add-on therapy to silodosin for patients with benign prostatic hyperplasia complicated by overactive bladder: A randomized, prospective trial using urodynamic studies.

AIMS: To compare the efficacy of fesoterodine or mirabegron add-on therapy for persistent overactive bladder (OAB) symptoms despite silodosin monotherapy in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, in both subjective and objective aspects. METHODS: A total of 120 patients with persistent OAB symptoms despite silodosin monotherapy were randomized to receive add-on therapy with fesoterodine (4 mg/day) or mirabegron (50 mg/day) for 12 weeks. At week 12, changes from baseline in patients' subjective symptoms and voiding/storage functions, as assessed using the International Prostate Symptom Score (IPSS), OAB symptom score (OABSS), and urodynamic studies, were compared between the groups. RESULTS: The final analysis included 50 and 52 patients in the fesoterodine and mirabegron groups, respectively. Although the IPSS and OABSS significantly improved in both groups, the fesoterodine (vs mirabegron) group showed significantly greater improvements in the OABSS-total (-2.8 vs -1.5, P = 0.004), IPSS-QOL (-1.5 vs -1.1, P = 0.04), and OABSS-urgency score (-1.5 vs -0.9, P = 0.008) at 12 weeks. Regarding storage functions, although both groups showed significant improvements, the fesoterodine group demonstrated greater improvements in the detrusor overactivity alleviation rate (52.6% vs 28.9%, P = 0.03). Voiding functions did not deteriorate in either group at 12 weeks; no significant inter-group differences were observed. Post-void residual urine significantly increased by 16 mL only in the fesoterodine group. CONCLUSION: Add-on therapy of fesoterodine to silodosin was more effective than adding mirabegron to silodosin for improving OAB symptoms and storage functions, without deteriorating voiding symptoms or functions.

The effect of herpes simplex virus vector-mediated gene therapy of protein phosphatase 1α on bladder overactivity and nociception.

AIMS: We studied the effect of herpes simplex virus (HSV) vectors-based gene transfer of protein phosphatase 1α (PP1α) on bladder hypersensitivity in rats. METHODS: Using adult female Sprague-Dawley rats, non-replicating HSV vectors carrying PP1α or green fluorescent protein (GFP) were injected into the bladder wall. At one week after vector inoculation, cystometry and Western blot assay were performed, whereas the other experiments were performed at 2 weeks after vector inoculation. RESULTS: GFP-expressing cells were identified in the bladder as well as in L6/S1 dorsal root ganglia at 14 days. In cystometry, intercontraction intervals (ICI) after resiniferatoxin (RTx; TRPV1 agonist) irrigation was significantly reduced in the PP1α group in comparison with the GFP group. Moreover, RTx-induced freezing behavior events were observed significantly more frequently in the PP1α group than the GFP group. The number of c-Fos positive cells in the L6 spinal dorsal horn was significantly less in the PP1α group than in the GFP group. Western blot assay revealed lower levels of phosphorylated inositol 1, 4, 5-triphosphate receptor (p-IP3 R), and phosphorylated TRPV1 in the PP1α compared with the GFP group. CONCLUSIONS: HSV vectors-mediated PP1α gene therapy may be an alternative treatment modality for cystitis-related hypersensitive bladder condition at least in part via modulation of the IP3 R signaling pathway.

What Are Factors Contributing to Improvement of Overactive Bladder Symptoms after Alpha-1 Blocker Treatment in Patients with Both Storage and Voiding Symptoms?

INTRODUCTION: To determine the pre-treatment factors related to the improvement of overactive bladder (OAB) symptom after alpha-1 blocker monotherapy in patients with benign prostatic hyperplasia complicated by OAB (BPH/OAB). METHODS: Post-hoc analysis of a prospective study in patients with BPH/OAB, randomized to receive silodosin 8 mg (n = 157) or naftopidil 75 mg (n = 157) treatment for 12 weeks, was performed. At 12 weeks post-administration, patients were divided into 2 groups (good responder [GR] group and poor responder [PR] group), according to the improvement in the OAB symptom score (OABSS). We compared the pre-administration parameters between both groups and evaluated the factors related to OAB improvement. RESULTS: Of 314 patients, 159 patients (50.6%) were classified into the GR and 155 (49.4%) into the PR. International Prostate Symptom score, total OABSS, OABSS urgency-score, OABSS urgency urinary incontinence (UUI)-score, post-void residual urine volume (PVR), and selection rate of naftopidil were significantly higher in the PR than in the GR. On multivariate logistic regression analysis, larger PVR, higher OABSS-UUI-score, and the choice of naftopidil were significant risk factors for insufficient improvement of OAB symptoms. CONCLUSIONS: Pre-treatment PVR, UUI severity, and the choice of treatment agent are predicting factors related to OAB improvement after alpha-1 blocker monotherapy in patients with BPH/OAB.

Urodynamic analysis of the impact of diabetes mellitus on bladder function.

OBJECTIVES: To analyze sequential changes of diabetic cystopathy based on urodynamic data in patients with diabetes mellitus. METHODS: Participants included male diabetes patients who underwent a pressure flow study at Nagoya University Graduate School of Medicine, Nagoya, Japan, from April 2005 to October 2016. Patients with a previous history of lower urinary tract dysfunction were excluded. Bladder dysfunction was categorized into four urodynamic patterns: (i) normal; (ii) detrusor overactivity with normal detrusor contractility; (iii) detrusor hyperreflexia/impaired contractility; and (iv) detrusor underactivity. The urodynamic patterns were evaluated according to the presence of diabetic retinopathy and nephropathy, which was correlated to diabetes mellitus duration. Furthermore, the association of clinical factors with voiding function, as well as sensory function, was investigated. RESULTS: A total of 57 patients were enrolled. Detrusor overactivity with normal detrusor contractility patterns was seen only in cases with neither diabetic retinopathy nor diabetic nephropathy, whereas the prevalence of detrusor hyperreflexia/impaired contractility pattern was highest in cases with diabetic retinopathy. Detrusor underactivity pattern was found with the highest frequency in cases with both diabetic retinopathy and diabetic nephropathy. On multivariate analysis, the existence of diabetic retinopathy was only significantly correlated with bladder contractility index. Furthermore, multivariate analysis showed that first desire volume and maximum cystometric capacity were significantly positively correlated with post-void residual urine volume, and also negatively correlated with voiding efficiency independent of bladder contractility index. CONCLUSIONS: Diabetes patients have diverse progressive bladder dysfunction according to the diabetes stage. An optimal screening program is necessary to detect and manage diabetic cystopathy at an early stage.

Treatment of male stress urinary incontinence using autologous adipose-derived regenerative cells: Long-term efficacy and safety.

OBJECTIVES: To investigate the long-term efficacy and safety of periurethral injection of autologous adipose-derived regenerative cells for the treatment of post-prostatectomy stress urinary incontinence. METHODS: A total of 13 patients with persistent stress urinary incontinence after prostate surgery (radical prostatectomy, 10 patients; holmium laser enucleation of the prostate, three patients) underwent periurethral injection of adipose-derived regenerative cells and were followed up for >4 years. A 24-h pad test was carried out for four consecutive days in each evaluation period, and changes in the mean daily leakage volume during the 4 days from baseline to 60 months after treatment were evaluated. RESULTS: The mean follow-up period was 69 months (range 55-72 months). The mean leakage volume/24 h in all patients changed from 260.7 g to 152.7 g. Urinary incontinence progressively improved up to 12 months after treatment in 10 patients, who maintained improvement up to the final assessment, with the mean daily leakage volume decreasing from 281.5 g to 119.0 g (reduction rate 57.7%). The other three patients showed no improvement at 1 year and at the final assessment. After the perioperative period, significant adverse events or prostate-specific antigen increase were not observed during long-term follow up. CONCLUSIONS: The present findings suggest that periurethral injection of autologous adipose-derived regenerative cells is a safe and feasible treatment modality with long-term efficacy for patients with male stress urinary incontinence caused by urethral sphincter deficiency.

Nerve growth factor-dependent hyperexcitability of capsaicin-sensitive bladder afferent neurones in mice with spinal cord injury.

NEW FINDINGS: What is the central question of this study? Nerve growth factor (NGF) is reportedly a mediator inducing urinary bladder dysfunction. Is NGF directly involved in hyperexcitability of capsaicin-sensitive C-fibre bladder afferent pathways after spinal cord injury (SCI)? What is the main finding and its importance? Neutralization of NGF by anti-NGF antibody treatment reversed the SCI-induced increase in the number of action potentials and the reduction in spike thresholds and A-type K+ current density in mouse capsaicin-sensitive bladder afferent neurones. Thus, NGF plays an important and direct role in hyperexcitability of capsaicin-sensitive C-fibre bladder afferent neurones attributable to the reduction in A-type K+ channel activity in SCI. ABSTRACT: Nerve growth factor (NGF) has been implicated as an important mediator in the induction of C-fibre bladder afferent hyperexcitability, which contributes to the emergence of neurogenic lower urinary tract dysfunction after spinal cord injury (SCI). In this study, we determined whether NGF immunoneutralization using an anti-NGF antibody (NGF-Ab) normalizes the SCI-induced changes in electrophysiological properties of capsaicin-sensitive C-fibre bladder afferent neurones in female C57BL/6 mice. The spinal cord was transected at the Th8/Th9 level. Two weeks later, continuous administration of NGF-Ab (10 µg kg-1  h-1 , s.c. for 2 weeks) was started. Bladder afferent neurones were labelled with Fast-Blue (FB), a fluorescent retrograde tracer, injected into the bladder wall 3 weeks after SCI. Four weeks after SCI, freshly dissociated L6-S1 dorsal root ganglion neurones were prepared. Whole-cell patch-clamp recordings were then performed in FB-labelled neurones. After recording action potentials or voltage-gated K+ currents, the sensitivity of each neurone to capsaicin was evaluated. In capsaicin-sensitive FB-labelled neurones, SCI significantly reduced the spike threshold and increased the number of action potentials during membrane depolarization for 800 ms. These SCI-induced changes were reversed by NGF-Ab. Densities of slow-decaying A-type K+ (KA ) and sustained delayed rectifier-type K+ currents were significantly reduced by SCI. The NGF-Ab treatment reversed the SCI-induced reduction in the KA current density. These results indicate that NGF plays an important role in hyperexcitability of mouse capsaicin-sensitive C-fibre bladder afferent neurones attributable to a reduction in KA channel activity. Thus, NGF-targeting therapies could be effective for treatment of afferent hyperexcitability and neurogenic lower urinary tract dysfunction after SCI.

Role of microglia in the spinal cord in colon-to-bladder neural crosstalk in a rat model of colitis.

AIMS: We investigated whether spinal cord microglia are involved in colon-to-bladder neural crosstalk in a rat model of colitis. METHODS: Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by administering 50% trinitrobenzene sulfonic acid into the distal colon in the colitis group and the minocycline group. Minocycline, a microglial inhibitor, was continuously infused into the intrathecal space in the minocycline group. The following investigations were performed on day 7: (1) continuous cystometry (CMG) in an awake condition; (2) nociceptive behavior observation induced by intravesical instillation of resiniferatoxin; (3) toluidine blue staining in the bladder; (4) Immunofluorescence staining for the microglial marker, CD11b, in L6 spinal cord sections; and (5) quantitative RT-PCR to investigate interleukin-1ß (IL-1ß), chemokine ligand 3 (CCL3), and brain-derived neurotrophic factor (BDNF) gene expression in the L6 spinal cord. RESULTS: In comparison with the control group, the colitis group showed significant increases in (1) micturition frequency during cystometry; (2) resiniferatoxin-induced freezing behavior (bladder pain); (3) the number of total and degranulated mast cells in the bladder; (4) the number of microglia in the L6 spinal cord, and (5) the expression of IL-1ß, CCL3, and BDNF mRNA in the L6 spinal cord. Moreover, intrathecal administration of minocycline alleviated these pathophysiological findings caused by experimental colitis. CONCLUSIONS: Spinal microglia may play an important role in colitis-induced bladder overactivity and enhanced bladder pain sensitivity in colitis rats.

Effect of TRPV4 activation in a rat model of detrusor underactivity induced by bilateral pelvic nerve crush injury.

AIMS: To produce an animal model of peripheral neurogenic detrusor underactivity (DU) and to evaluate the effect of TRPV4 receptor activation in this DU model. METHODS: In female Sprague-Dawley rats, bilateral pelvic nerve crush (PNC) was performed by using sharp forceps. After 10 days, awake cystometrograms (CMG) were recorded in sham and PNC rats. A TRPV4 agonist (GSK 1016790A) with or without a TRPV4 antagonist (RN1734) were administered intravesically and CMG parameters were compared before and after drug administration in each group. The TRPV4 transcript level in the bladder mucosa and histological changes were also evaluated. RESULTS: In CMG, PNC rats showed significant increases in intercontraction intervals (ICI), number of non-voiding contractions (NVCs), baseline pressure, threshold pressure, bladder capacity, voided volumes, and post-void residual (PVR) compared to sham rats. Contraction amplitude and voiding efficiency were significantly decreased in PNC rats. In PNC rats, intravesical application of GSK1016790A (1.5 µM) significantly decreased ICI, bladder capacity, voided volume, and PVR without increasing NVCs, and these effects were blocked by RN1734 (5.0 µM). In contrast, 1.5 µM GSK1016790A had no significant effects on CMG parameters in normal rats. TRPV4 expression within the bladder mucosa of PNC rats was increased in association with urothelial thickening. CONCLUSIONS: Rats with bilateral PNC showed characteristics of DU, and this model seems appropriate for further evaluation of peripheral neurogenic mechanisms of DU. Also, TRPV4 receptors, the activation of which reduced bladder capacity and PVR, could be a target for DU treatment.

Effects of Withdrawing α1-Blocker from Combination Therapy with α1-Blocker and 5α-Reductase Inhibitor in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: A Prospective and Comparative Trial Using Urodynamics.

PURPOSE: We compared the effects on lower urinary tract symptoms and bladder outlet obstruction of combination therapy with α1-blocker and 5α-reductase inhibitor or a switch to 5α-reductase inhibitor monotherapy. We determined the factors influencing changes in lower urinary tract symptoms after α1-blocker withdrawal. MATERIALS AND METHODS: A total of 140 outpatients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia received combination therapy with silodosin 8 mg per day and dutasteride 0.5 mg per day for 12 months. Of the patients 132 were randomized to continue combination therapy or switched to dutasteride monotherapy through silodosin withdrawal as the monotherapy group. Parameter changes from before randomization to 12 months after randomization were assessed based on subjective symptoms and urodynamic findings of voiding and storage function. RESULTS: Efficacy analysis included 57 patients on combination therapy and 60 on monotherapy. The change in I-PSS (International Prostate Symptom Score) after randomization was -0.7 and -0.6 in the combination therapy and monotherapy groups, respectively. The bladder outlet obstruction index changed from 46.1 to 41.8 in the combination therapy group and from 42.9 to 39.9 in the monotherapy group. No significant differences in subjective symptoms and bladder outlet obstruction were observed between the 2 groups. However, storage function decreased in the monotherapy group and lower urinary tract symptoms deteriorated significantly after the switch to dutasteride monotherapy in patients with a higher body mass index. CONCLUSIONS: We found that α1-blocker withdrawal from combination therapy was reasonable and tolerable with regard to the effect on lower urinary tract symptoms and bladder outlet obstruction. However, withdrawal must be performed carefully in patients with a high body mass index.

Comparison of Silodosin and Naftopidil for Efficacy in the Treatment of Benign Prostatic Enlargement Complicated by Overactive Bladder: A Randomized, Prospective Study (SNIPER Study).

PURPOSE: We investigated the efficacy of 2 α1-blockers with different affinities for the α1-adrenoceptor subtypes silodosin and naftopidil in the treatment of benign prostatic enlargement complicated by overactive bladder. MATERIALS AND METHODS: This was a prospective, open label, randomized, multicenter study of 350 outpatients with untreated benign prostatic enlargement associated with urinary urgency at least once per week and an OABSS (Overactive Bladder Symptom Score) of 3 or greater. Patients were randomly assigned to receive silodosin 8 mg per day or naftopidil 75 mg per day. Changes in parameters from baseline to 4 and 12 weeks were assessed based on I-PSS (International Prostate Symptom Score), I-PSS quality of life, OABSS and voiding functions measured by uroflowmetry. RESULTS: On efficacy analysis a total of 314 patients were included in the 2 groups. No significant difference in adverse effects was observed between the groups. Mean I-PSS and I-PSS quality of life scores, and OABSS significantly improved in both groups. Statistically significantly greater improvement in the silodosin group than in the naftopidil group was observed in total OABSS (p = 0.03), I-PSS quality of life score (p = 0.005) and OABSS urgency score (p <0.001) at 12 weeks. In regard to voiding function the maximum urinary flow rate showed significant improvements in both groups but the change in the maximum flow rate in the silodosin group at 12 weeks was significantly greater than in the naftopidil group (3.6 vs 2.1 ml per second). CONCLUSIONS: Silodosin, a pure α1A-adrenoceptor blocker, showed greater improvement in overactive bladder symptoms along with the urinary flow rate in patients with benign prostatic enlargement complicated by overactive bladder compared to naftopidil, an α1D>A-adrenoceptor blocker.

Combinational effects of muscarinic receptor inhibition and ß3-adrenoceptor stimulation on neurogenic bladder dysfunction in rats with spinal cord injury.

AIMS: To investigate the effects of combined therapy with an anticholinergic agent and a ß3-adrenoceptor agonist on bladder dysfunction and proliferation-related molecule expression in rats with spinal cord injury (SCI). METHODS: The spinal cord was transected at the level of T8-9 in female Sprague-Dawley rats, which were divided into four groups; A: Vehicle, B: 10 mg/kg/day of oxybutynin, C: 10 mg/kg/day of mirabegron, and D: combined administration of oxybutynin and mirabegron. Drugs were administered by oral gavage from 2 to 4 weeks after spinal cord transection. We evaluated urodynamic parameters and bladder tissue remodeling factors. RESULTS: Non-voiding contractions (NVCs) during the storage phase of cystometrograms tended to be decreased in all three treated groups with a significant reduction in group D versus A. Bladder compliance was improved, and intercontraction intervals, voided volume and bladder capacity were increased in group D. In all three treated groups (B-D), the expression of HIF1-α and TGF-ß1 was decreased compared to group A. The expression of collagen-III and bFGF was decreased in groups B and D. The total bladder elastin level was increased in group D. CONCLUSIONS: The combination therapy of an anticholinergic agent and a ß3-adrenoceptor agonist elevated the bladder elastin level, reduced NVCs, and increased bladder compliance more effectively than the monotherapy in SCI rats. Thus, the combination therapy could be effective for the treatment of neurogenic bladder dysfunction including bladder remodeling. Neurourol. Urodynam. 36:1039-1045, 2017. © 2016 Wiley Periodicals, Inc.

Long-term efficacy of a combination therapy with an anticholinergic agent and an α1-blocker for patients with benign prostatic enlargement complaining both voiding and overactive bladder symptoms: A randomized, prospective, comparative trial using a urodynamic study.

AIMS: We evaluated long-term efficacy and safety of a combination therapy (CT) with an anticholinergic agent and an α1-blocker for patients with benign prostatic enlargement (BPE) complaining of voiding and overactive bladder (OAB) symptoms, in comparison with those of α1-blocker monotherapy (MT), by conducting a urodynamic study (UDS). METHODS: This was a randomized prospective study involving 120 outpatients with untreated BPE associated with urinary urgency at least once per week and OABSS of ≥3. The patients were randomly assigned to receive MT with silodosin at 8 mg/day or CT with silodosin at 8 mg/day and propiverine at 20 mg/day. Changes in parameters from baseline to 12 weeks and 1 year after administration were assessed based on IPSS, IPSS-QOL, OABSS, and voiding and storage functions as measured by UDS. RESULTS: In efficacy analysis, 53 patients with MT and 51 with CT were included. Although mean IPSS and OABSS significantly improved in both groups, the CT group showed statistically significant improvement in OABSS (-3.4 in CT, -2.4 in MT, P = 0.04), IPSS-QOL (-1.9, -1.2, P = 0.01), and OAB-urgency score (-1.8, -1.2, P < 0.01) at the long-term evaluation. In storage function, both groups showed significant improvements, but the CT group demonstrated a greater improvement in terms of disappearance rate of detrusor overactivity (54.5% in CT, 34.2% in MT, P = 0.07) and bladder capacity (+61 mL, +33 mL, P = 0.02). CONCLUSIONS: Long-term combination treatment with silodosin and propiverine was effective and safe for BPE patients with voiding and OAB symptoms. Neurourol. Urodynam. 36:748-754, 2017. © 2016 Wiley Periodicals, Inc.

Post-injury bladder management strategy influences lower urinary tract dysfunction in the mouse model of spinal cord injury.

AIMS: To examine the effects of a different number of daily bladder squeezes on bladder dysfunction in mice with spinal cord injury (SCI). METHODS: Spinal cord was transected at the Th8/9 in female C57BL/6N mice. Their bladders were manually squeezed to eliminate urine inside every day for 4 weeks. The mice were divided into three groups depending on the number of bladder squeezes; A: once daily, B: twice daily, C: three times daily. Four weeks after transection, single-filling cystometry were performed under an awake condition. NGF in the bladder mucosa and mRNA expression of P2X receptors and TRP channels in L6/S1 dorsal root ganglia (DRG) were measured. RESULTS: Bladder weight in group C was less than that of group A. Bladder capacity, post-void residual, and the number of non-voiding contractions during the storage phase were significantly larger in group A compared to group B or C. The level of NGF in groups C were lower compared to group A or B. The expression of P2X3 and TRPA1 in groups B and C was decreased compared to group A. The expression of P2X2 was decreased in groups B compared to group A. CONCLUSION: The post-injury bladder management after SCI with an increased number of daily bladder emptying improves the storage and voiding bladder dysfunction associated with the reduction of NGF in the bladder as well as P2X and TRP transcripts in lumbosacral DRG.

Intravesical application of rebamipide suppresses bladder inflammation in a rat cystitis model.

PURPOSE: We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model. MATERIALS AND METHODS: Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters. RESULTS: Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1ß, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide. CONCLUSIONS: Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis.

Intravesical application of rebamipide promotes urothelial healing in a rat cystitis model.

PURPOSE: Rebamipide is used as a topical therapeutic agent for various organs. We examined the healing effects of intravesical rebamipide on damaged urothelium in a rat model of chemically induced cystitis. MATERIALS AND METHODS: Hydrochloride was injected in the bladder of female Sprague Dawley® rats to induce cystitis. On days 1 and 4 rebamipide (1 or 10 mM) or vehicle was administered in the bladder and maintained for 1 hour. Histopathology, urothelial permeability, cystometrogram and nociceptive behaviors were evaluated on day 7. Also, tissue rebamipide concentrations after the 1-hour bladder instillation were quantified using high performance liquid chromatography. RESULTS: Intravesically administered rebamipide permeated the bladder, particularly in hydrochloride treated rats, and the pharmacologically effective tissue dose remained for greater than 6 hours. Bladder histological evaluation revealed polymorphological inflammatory cell infiltration and decreased positive staining for uroplakin 3A in hydrochloride treated rats. Scanning electron microscopy showed damaged tight junctions in the hydrochloride group. Evans blue absorption in the bladder wall was increased in hydrochloride treated rats. These findings, which were associated with urothelial injury and increased permeability, were dependently suppressed by the rebamipide treatment dose. Cystometrogram demonstrated that the intercontraction interval was shorter in hydrochloride treated rats but prolonged by rebamipide. The increased nociceptive behaviors observed after intravesical resiniferatoxin administration were also suppressed by rebamipide. CONCLUSIONS: Intravesical rebamipide accelerated the repair of damaged urothelium, protected urothelial barrier function and suppressed bladder overactivity and nociception.