Protective effect of equol intake on bladder dysfunction in a rat model of bladder outlet obstruction.

OBJECTIVES: This study evaluates the impact of equol, a metabolite of soy isoflavone, on bladder dysfunction in rats with bladder outlet obstruction (BOO). In addition, we investigate its potential as a neuroprotective agent for the obstructed bladder and discuss its applicability in managing overactive bladder (OAB). METHODS: Eighteen male Sprague-Dawley rats were divided into three groups (six rats per group) during the rearing period. The Sham and C-BOO groups received an equol-free diet, while the E-BOO group received equol supplementation (0.25 g/kg). At 8 weeks old, rats underwent BOO surgery, followed by continuous cystometry after 4 weeks of rearing. The urinary oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde) were measured, and the bladder histology was analyzed using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining (neurofilament heavy chain for myelinated nerves, peripherin for unmyelinated nerves, and malondialdehyde). RESULTS: Equol reduced BOO-induced smooth muscle layer fibrosis, significantly prolonged the micturition interval (C-BOO: 193 s, E-BOO: 438 s) and increased the micturition volume (C-BOO: 0.54 mL, E-BOO: 1.02 mL) compared to the C-BOO group. Equol inhibited the increase in urinary and bladder tissue malondialdehyde levels. While the C-BOO group exhibited reduced peripherin alone positive nerve fibers within the smooth muscle layer, equol effectively attenuated this decline. CONCLUSIONS: Equol reduces lipid peroxidation and smooth muscle layer fibrosis in the bladder and exhibited neuroprotective effects on bladder nerves (peripheral nerves) and prevented the development of bladder dysfunction associated with BOO in rats. Consumption of equol is promising for the prevention of OAB associated with BOO.

Defining urge as an uncontrolled micturition explains pathogenesis, informs cure and helps solve the burgeoning OAB crisis.

BACKGROUND: Parallel with the demographic ageing crisis, is a disabling overactive bladder (OAB) crisis (urgency/frequency/nocturia), 30% prevalence in older women, pathogenesis stated as unknown and, according to some learned societies, incurable. HYPOTHESIS/AIMS: To review International Continence Society and Integral System paradigms to test our thesis that OAB per se is not a pathological condition, rather, a prematurely activated uncontrolled micturition; pathogenesis being anatomical damage in a nonlinear feedback control system comprising cortical and peripheral (muscle/ligament) components. METHODS: We examined studies from basic science, anatomy, urodynamics, ultrasonic and video xrays, ligament repairs, from which we created a nonlinear binary model of bladder function. We applied a Chaos Theory feedback equation, Xnext = Xc(1 - X) to test our hypothesis against existing concepts and hypotheses for OAB pathogenesis. RESULTS: The bladder has ONLY two modes, EITHER closed OR open (micturition). Closure is reflexly controlled cortically and peripherally: muscles contracting against ligaments stretch the vagina to suppress afferent signals to micturate from urothelial stretch receptors. "OAB" can be caused by anatomical damage anywhere in the model, by childbirth or age-weakened ligaments, which can be repaired to cure all three OAB symptoms. Urodynamic "DO" graphs are interpreted anatomically and by the feedback equation. CONCLUSION: OAB is in crisis. Our thesis of OAB as an uncontrolled micturition from anatomical defects in the bladder control system provides fresh directions for further development of new treatments, nonsurgical and surgical, to help break the crisis and bring hope and cure to 600 million women sufferers.

Overactive Bladder in Frail Older Adults.

Overactive bladder (OAB) and frailty are multidimensional syndromes, and the prevalence of both increases with age. Little evidence exists for a direct association between OAB and frailty, but urinary urgency may well be a precursor of frailty in older people. Frail older adults are no less deserving of treatment than fit older adults, and lifestyle, behavioral, and pharmacological interventions remain the primary options for treatment, with some evidence for efficacy. Data on onabotulinumtoxinA therapy or percutaneous tibial nerve stimulation in frail older adults are sparse. Frail older adults are often excluded from drug trials, but evidence is accumulating that antimuscarinics and, to a lesser extent, beta-adrenergic agonists are safe, well-tolerated, and effective in older adults. Cognitive impairment associated with frailty should not be used as justification for avoiding the use of antimuscarinics. More studies are required to better understand the association between OAB and frailty, as both are associated with poor outcomes and may be amenable to intervention. Drug trials for OAB treatments should be encouraged to include frail older adults, as this population is highly affected yet often excluded.

Mirabegron in the Treatment of Overactive Bladder: Safety and Efficacy in the Very Elderly Patient.

Lower urinary tract symptoms, including urgency, urgency incontinence, frequency, and nocturia, are highly prevalent in older adults and are associated with significant morbidity and impairment in quality of life. When conservative measures such as bladder training fail to improve symptoms, pharmacological management is recommended by national and international guidelines. Mirabegron, an agonist of the ß3 adrenergic receptor, demonstrates similar efficacy to the anticholinergic drugs without the risk of anticholinergic effects, but experience and evidence in the very elderly population are limited. This narrative review examines the current evidence base for mirabegron in very elderly adults.

Update from TASCI, a Nationwide, Randomized, Sham-controlled, Double-blind Clinical Trial on Transcutaneous Tibial Nerve Stimulation in Patients with Acute Spinal Cord Injury to Prevent Neurogenic Detrusor Overactivity.

Transcutaneous tibial nerve stimulation has the potential to revolutionize the management of lower urinary tract dysfunction in patients with acute spinal cord injury. TASCI is a nationwide randomized, sham-controlled, double-blind clinical trial for which the preparatory phase has been successfully completed.

The influence of nebivolol on the activity of BRL 37344 - the ß3-adrenergic receptor agonist, in the animal model of detrusor overactivity.

AIMS: The cardiotoxic effects of antimuscarinics constitute a significant restriction in their application in elderly people. Overactive bladder syndrome pharmacotherapy using compounds with cardioprotective properties would seem an ideal solution. The main goal of the study was to assess the impacts of nebivolol (NEB) on the activity of BRL 37344 - ß3-adrenergic receptor (ß3AR) agonist, in the animal model of detrusor overactivity. As both these substances can impact on the cardiovascular system, their effect on the parameters of this system and diuresis was also examined. METHODS: Retinyl acetate (RA; 0.75%) solution was used to induce detrusor overactivity in female Wistar rats. BRL and/or NEB were administered intra-arterially during cystometry in a single dose (2.5 or 5, 0.05 or 0.1 mg/kg, respectively). In addition, a 24 hours measurement of heart rate, blood pressure, and urine production was carried out. RESULTS: NEB (0.05 mg/kg) and BRL (2.5 mg/kg) monotherapy proved to have no influence on the cystometric parameters of animals with RA-induced detrusor overactivity. NEB at 0.1 mg/kg resulted in a drop in the detrusor overactivity index, similarly to BRL at 5 mg/kg. Coadministration of NEB and BRL, both at ineffective doses, decreased the detrusor overactivity index and ameliorated the nonvoiding contractions. ß3AR stimulation proved to induce tachycardia and hypertension. NEB at 0.05 mg/kg proved to ameliorate detrusor overactivity and have preventive properties against adverse cardiovascular effects of the ß3AR agonist. CONCLUSIONS: The combined application of the ß3AR agonist and NEB may improve detrusor overactivity without affecting the heart rate, blood pressure, and urine production.

"A secret club": focus groups about women's toileting behaviors.

BACKGROUND: Understanding reasons for and impact of women's toileting behaviors on bladder health is important to prevent and manage urinary incontinence (UI) and overactive bladder (OAB). METHODS: Women, regardless of urinary incontinence (UI) and overactive bladder (OAB) status, were recruited in Pennsylvania and North Carolina. Focus groups were conducted by trained female moderators and sessions were audiotaped. Participants completed an anonymous questionnaire containing validated items to determine the presence of UI and OAB. Audiotapes were transcribed and content was analyzed by two investigators to identify themes. RESULTS: Twenty-four women participated (mean age 68 ± 13.4 years); most had UI (75%) or OAB (87.5%). Many women had difficulty in describing bladder health, and talked about bladder function, diseases or conditions, and control over the bladder. Four themes about toileting emerged: 1) cues/triggers/alerts women used to find and use toilets, 2) toilet cleanliness away from and at home, 3) toileting as a nuisance, and 4) situational awareness. Women described internal (e.g., sensation of heaviness) and external cues/triggers/alerts (e.g., walking by restrooms), and the trade-off between their concerns about public toilet cleanliness and the need to urinate. Some women expressed being irritated or annoyed about having to stop activities to urinate. Most women reported sitting on their home toilets, whereas, many hovered or stood over the toilet in public places. CONCLUSIONS: The information gained from this study will facilitate the development of relevant public health messaging and interventions to raise public awareness about UI, OAB, and bladder health with the aim to encourage women to seek help when symptoms are present.

A medical device containing purified bovine colostrum (Monurelle Biogel) in the treatment of vulvovaginal atrophy in postmenopausal women: Retrospective analysis of urinary symptoms, sexual function, and quality of life.

OBJECTIVE: This study assessed the effectiveness and safety of a medical device containing purified bovine colostrum (Monurelle Biogel; Zambon, Bresso, Italy) in improving vulvovaginal atrophy (VVA), sexual function, urinary symptoms, and quality of life (QoL) in postmenopausal women. METHODS: In all, 172 postmenopausal women with VVA were included in the study. All women were treated with vaginal Monurelle Biogel daily for 12 weeks. Patients underwent clinical examinations, completed a 3-day voiding diary, and had VVA graded using the Vaginal Health Index (VHI) at baseline and 12 weeks. Patients also completed the Female Sexual Function Index (FSFI), overactive bladder questionnaire (OAB-Q), and the Urogenital Distress Inventory (UDI-6), among others. RESULTS: After 12 weeks, there were significant increases in mean (± SD) VHI (12.53 ± 3.67 vs. 19.31 ± 3.49; P < .0001), the number of patients engaging in regular sexual activity 102 (59.3%) vs. 144 (83.7%), and in the total FSFI score (21.64 ± 2.99 vs. 28.16 ± 1.93; P < .0001) compared with baseline. In addition, there were significant reductions in the mean number of 24-hour voids (9.57 ± 2.12 vs. 7.13 ± 1.22; P < .0001), urgent micturition episodes per 24 hours (1.75 ± 0.76 vs. 1.14 ± 0.87; P = .001), nocturia episodes (1.58 ± 0.85 vs. 0.97 ± 1.18; P = .0002), and urinary incontinence episodes per 24 hours (0.74 ± 0.59 vs. 0.28 ± 0.52; P = .003). Finally, after 12 weeks treatment, there were significant differences in UDI-6 (7.85 ± 0.81 vs. 5.56 ± 1.40), OAB-Q symptom (53.60 ± 12.57 vs. 22.08 ± 9.63), and OAB-Q health-related QoL (21.75 ± 8.51 vs. 69.34 ± 14.59) scores compared with baseline (P < .0001 for all). The Patient Impression of Global Improvement scale revealed global improvement in 143 women (83.14%). CONCLUSIONS: Monurelle Biogel is an effective treatment for VVA in postmenopausal women, improving sexual life, urinary symptoms, and QoL.

Overactive Bladder Symptoms after Transobturator Sling Surgery for Pure Stress Urinary Incontinence: A Cross-Sectional Comparative Study.

INTRODUCTION: Transobturator tape (TOT) surgery has been associated with increased overactive bladder (OAB) although much controversy exists. METHODS: In a cross-sectional study, women who underwent TOT surgery for pure stress incontinence (MonarcTM) answered the 6 questions of the symptom bother (SB) subscale of the OAB questionnaire - short form (OABq-SF) and an additional question regarding whether symptoms began after surgery. Women with SB score over the 4th quartile (≥30/100) were reassessed after a longer follow-up. Patients from primary care were recruited as controls. RESULTS: We recruited 213 patients (135 in the TOT group and 78 age-adjusted controls). The mean age of operated patients was 58.7 ± 10.1 years with a mean follow-up of 25.9 ± 13.2 months. OABq-SF SB scores did not differ between the TOT group and controls (respectively, 18.5 ± 30 and 15.5 ± 6.7, p = 0.202). A total of 48% patients reported no relationship between symptoms and surgery. Highly symptomatic operated patients were reassessed after a longer follow-up (46.3 ± 10.6 months). The mean score in the second follow-up (n = 25) was not statistically different from the first assessment (46.4 ± 22.7 and 58.1 ± 19.8, p = 0.059). CONCLUSIONS: Women who underwent TOT surgery did not show increased OAB SB scores when compared to controls. Our study suggests that OAB symptoms may thus be present but overlooked during initial clinical assessment.

The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice.

We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 wk after SCI. Female C57BL/6N mice were divided into four groups: 1) spinal intact (SI)-control, 2) SI-capsaicin pretreatment (Cap), 3) SCI-control, and 4) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition. In the Cap groups, capsaicin (25, 50, or 100 mg/kg) was injected subcutaneously 4 days before the experiments. In the SI-Cap group, 100 mg/kg capsaicin pretreatment significantly increased bladder capacity and decreased the silent period duration of EUS/EMG compared with the SI-control group. In the SCI-Cap group, 50 and 100 mg/kg capsaicin pretreatment decreased the number of nonvoiding contractions (NVCs) and the duration of reduced EUS activity during voiding, respectively, compared with the SCI-control group. In SCI mice, hexamethonium, a ganglionic blocker, almost completely blocked NVCs, suggesting that they are of neurogenic origin. Patch-clamp recordings in capsaicin-sensitive bladder afferent neurons from SCI mice showed hyperexcitability, which was evidenced by decreased spike thresholds and increased firing rate compared with SI mice. These results indicate that capsaicin-sensitive C-fiber afferent pathways, which become hyperexcitable after SCI, can modulate bladder and urethral sphincter activity in awake SI and SCI mice. Detrusor overactivity as shown by NVCs in SCI mice is significantly but partially dependent on capsaicin-sensitive C-fiber afferents, whereas the EUS relaxation during voiding is enhanced by capsaicin-sensitive C-fiber bladder afferents in SI and SCI mice.

Adherence and persistence of mirabegron and anticholinergic therapies in patients with overactive bladder: a real-world claims data analysis.

BACKGROUND: Adherence and persistence rates of anticholinergic (ACH) therapies have been well described. To date, few studies describe these metrics for mirabegron in patients with overactive bladder. METHODS: This retrospective analysis of MarketScan® database assessed adherence and persistence of patients receiving either mirabegron or ACH. Study eligibility required an index date (first prescription filled) between July 2012 and June 2013 with 12 months of continuous enrolment preindex date and 12 months of follow-up. Adherence was defined as a proportion of days covered of ≥ 80% among patients with at least 2 fills of index medication. Persistence measures included treatment failure described as either treatment discontinuation (medication supply gap ≥ 30 days) or switching to a different medication. A medication supply gap of ≥ 45 days was used as a sensitivity analysis. RESULTS: The mean age of mirabegron users (n = 4037) was 67 years and 43% were ACH naïve while the mean age of ACH users was 62 years (n = 67,943). Over the 12-month follow-up period, 44% of patients treated with mirabegron and 31% of patients treated with ACH were adherent to their indexed medications. Treatment failure was 81% for mirabegron and 88% for ACH. Most mirabegron treatment failures were because of treatment discontinuation (67%) versus switching to ACH therapy (14%). The ACH discontinuation rate was 84% and treatment switching rate was 4%. The mean (standard deviation) time to treatment failure was 143 (130) days for mirabegron and 69 (69) days for ACH. Adherence and persistence patterns were similar in the sensitivity analysis using a ≥ 45-day supply gap threshold. CONCLUSIONS: This real-world study demonstrated low adherence and persistence to mirabegron similar to ACH therapies.

Sex difference in the contribution of GABAB receptors to tibial neuromodulation of bladder overactivity in cats.

This study investigated the role of γ-aminobutyric acid subtype B (GABAB) receptors in tibial and pudendal neuromodulation of bladder overactivity induced by intravesical administration of dilute (0.5%) acetic acid (AA) in α-chloralose-anesthetized cats. To inhibit bladder overactivity, tibial or pudendal nerve stimulation (TNS or PNS) was applied at 5 Hz and two or four times threshold (T) intensity for inducing toe or anal sphincter twitch. TNS at 2T or 4T intensity significantly (P < 0.05) increased the bladder capacity to 173.8 ± 16.2 or 198.5 ± 24.1%, respectively, of control capacity. Meanwhile, PNS at 2T or 4T intensity significantly (P < 0.05) increased the bladder capacity to 217 ± 18.8 and 221.3 ± 22.3% of control capacity, respectively. CGP52432 (a GABAB receptor antagonist) at intravenous dosages of 0.1-1 mg/kg completely removed the TNS inhibition in female cats but had no effect in male cats. CGP52432 administered intravenously also had no effect on control bladder capacity or the pudendal inhibition of bladder overactivity. These results reveal a sex difference in the role of GABAB receptors in tibial neuromodulation of bladder overactivity in cats and that GABAB receptors are not involved in either pudendal neuromodulation or irritation-induced bladder overactivity.

Imprisoned in the Cultural Stereotypes of Overactive Bladder: Cultural Meanings of Disease and Sick Role Adaptation in Hong Kong.

BACKGROUND: Diseases often carry cultural meanings and metaphors, and these meanings can influence illness experiences and behavioral responses. OBJECTIVES: This research investigated how old cultural stereotypes and new social understandings of overactive bladder (OAB) intertwined to influence sick role adaptation and behavioral responses among those with OAB. METHODS: A qualitative approach using in-depth individual, semistructured interviews was adopted. Thirty patients having OAB were purposively sampled from a patient self-help group for people with OAB. RESULTS: The cultural stereotypes about OAB-as an "old people" disease, as a hopeless disease without cure, as a sexually related disease, and as a disease of substance use-had significant impact on the social and illness experiences of participants, leading to difficulty in adapting to their sick role, indicated by behavioral responses of denial, concealment, resignation, and self-seclusion. DISCUSSION: Cultural stereotypes of OAB significantly influenced sick role adaptation, which affected illness experiences of persons with OAB. These cultural stereotypes were associated with behavioral responses that led to difficulties in coping with OAB.

Activation of bitter taste receptors (tas2rs) relaxes detrusor smooth muscle and suppresses overactive bladder symptoms.

Bitter taste receptors (TAS2Rs) are traditionally thought to be expressed exclusively on the taste buds of the tongue. However, accumulating evidence has indicated that this receptor family performs non-gustatory functions outside the mouth in addition to taste. Here, we examined the role of TAS2Rs in human and mouse detrusor smooth muscle (DSM). We showed that mRNA for various TAS2R subtypes was expressed in both human and mouse detrusor smooth muscle (DSM) at distinct levels. Chloroquine (CLQ), an agonist for TAS2Rs, concentration-dependently relaxed carbachol- and KCl-induced contractions of human DSM strips. Moreover, 100 µM of CLQ significantly inhibited spontaneous and electrical field stimulation (EFS)-induced contractions of human DSM strips. After a slight contraction, CLQ (1 mM) entirely relaxed carbachol-induced contraction of mouse DSM strips. Furthermore, denatonium and quinine concentration-dependently decreased carbachol-induced contractions of mouse DSM strips. Finally, we demonstrated that CLQ treatment significantly suppressed the overactive bladder (OAB) symptoms of mice with partial bladder outlet obstruction (PBOO). In conclusion, we for the first time provide evidence of the existence of TAS2Rs in the urinary DSM and demonstrate that TAS2Rs may represent a potential target for OAB. These findings open a new approach to develop drugs for OAB in the future.

Ovariectomy May Induce Detrusor Overactivity in Rats: The Therapeutic Role of Rho Kinase Inhibition.

OBJECTIVE: To verify the impact of ovariectomy (OVX) on the micturition cycle in conscious rats; to examine the influence of rho kinase (ROCK) inhibition on the bladder detrusor in OVX rats; to assess the effect of the joint administration of the ROCK inhibitor (GSK 269962) and solifenacin succinate (SOL) to these animals. MATERIALS AND METHODS: The impact of OVX or a single dose of GSK 269962 and/or SOL on the cystometric parameters was assessed 28 days after the procedure. RESULTS: OVX caused an increase in detrusor overactivity index, amplitude, and frequency of nonvoiding contractions, along with a decrease in voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. GSK 269962 administered in a dose of 10 mg/kg (but not 5 mg/kg) or SOL in a dose of 0.03 mg/kg (but not 0.015 mg/kg) triggered an increase in voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions, along with a decrease in detrusor overactivity index, amplitude, and frequency of nonvoiding contractions. A combined administration of GSK 269962 (5 mg/kg) and SOL (0.15 mg/kg), in doses ineffective in monotherapy, triggered a reversal in the OVX-induced cystometric changes. CONCLUSION: It appears that ROCK inhibitors can become an alternative worth considering in overactive bladder syndrome treatment, especially in the light of the findings pointing to the decreased efficiency of antimuscarinic drugs in the overactive bladder syndrome treatment of postmenopausal women.

Preventive Effect of Hydrogen Water on the Development of Detrusor Overactivity in a Rat Model of Bladder Outlet Obstruction.

PURPOSE: Bladder ischemia and oxidative stress contribute to the pathogenesis of bladder dysfunction caused by bladder outlet obstruction. H2 reportedly acts as an effective antioxidant. We investigated whether oral ingestion of H2 water would have a beneficial effect on bladder function in a rat model of bladder outlet obstruction. MATERIALS AND METHODS: H2 water was made by dissolving H2 gas in ordinary drinking water using a hydrogen water producing apparatus. The bladder outlet obstruction model was surgically induced in male rats. Rats with obstruction were fed H2 water or ordinary drinking water. On week 4 postoperatively cystometry was performed. Oxidative stress markers and the bladder nerve growth factor level were determined. Bladder tissues were processed for pharmacological studies and histological analysis. RESULTS: The micturition interval and micturition volume significantly decreased in obstructed rats given ordinary drinking water. These decreases were significantly suppressed by oral ingestion of H2 water. Increased post-void residual volume in obstructed rats was significantly reduced by H2 water. Obstruction led to a significant increase in bladder weight, oxidative stress markers and nerve growth factor. H2 water significantly suppressed these increases without affecting bladder weight. There was no significant difference in histological findings between rats with bladder obstruction given H2 water and ordinary drinking water. Decreased responses of detrusor muscle strips from obstructed bladders to KCl, carbachol and electrical field stimulation were reversed by H2 water ingestion. CONCLUSIONS: Results suggest that H2 water could ameliorate bladder dysfunction secondary to bladder outlet obstruction by attenuating oxidative stress.

Impact of Rho-Kinase Inhibitor Hydroxyfasudil in Protamine Sulphate Induced Cystitis Rat Bladder.

OBJECTIVES: The objective of the present study was to evaluate anti-inflammatory effects of hydroxyfasudil in a protamine sulfate (PS) induced cystitis rat model. Additionally, we investigated prevention of bladder overactivity (BO), and tissue damage in these experiments. METHODS: Animals were divided into four groups. In Groups 1 and 2, chemical induced cystitis model was created by administrating intravesical PS with PE50 catheter by the transurethral route. In Group 1, Rho-kinase inhibitor hydroxyfasudil was administered intaperitoneally, and in Group 2, subjects were administered a corresponding volume of saline in the same way. In Group 3, vehicle was administered intravesically and hydroxyfasudil was administrated intraperitoneally. Group 4 was a control Group, and the vehicle was administered intravesically and intraperitoneally. Micturition frequencies were recorded. Biochemical analyses were performed for oxidative stress, and pathological evaluations were investigated. In vitro contractions of bladder tissue strips were measured in tissue-bath. RESULTS: There were significantly lower Lipid peroxidase levels and higher levels of Glutathione in Group 1 than Group 2 (P = 0.016, P = 0.001, respectively). There was generally more inflammation in Group 2 than the other groups as determined by microscopy. There were significantly higher frequencies of micturition, lower volume, and mean voided maximum urine output after PS administration in Groups 1 and 2. In vitro contraction responses of bladder strips to potassium chloride and acetylcholine were statistically higher in Group 2 than Groups 1 and 3. CONCLUSIONS: Significant reduction of inflammation by affecting the anti-oxidant defense systems was provided by hydroxyfasudil. Decreased in vitro responses to contractions of bladder smooth muscle strips were obtained. Hydroxyfasudil may be a potential new therapeutic option for inflammation and BO, in rat bladder.

The role of the peripheral cannabinoid system in the pathogenesis of detrusor overactivity evoked by increased intravesical osmolarity in rats.

The cannabinoid receptors CB1 and CB2 are localized in the urinary bladder and play a role in the regulation of its function. We investigated the pathomechanisms through which hyperosmolarity induces detrusor overactivity (DO). We compared urinary bladder activity in response to blockade of CB1 and CB2 receptors using AM281 and AM630, respectively, in normal rats and after hyperosmolar stimulation. Experiments were performed on 44 rats. DO was induced by intravesical instillation of hyperosmolar saline. Surgical procedures and cystometry were performed under urethane anaesthesia. The measurements represent the average of 5 bladder micturition cycles. We analysed basal, threshold, and micturition voiding pressure; intercontraction interval; compliance; functional bladder capacity; motility index; and detrusor overactivity index. The blockage of CB1 and CB2 receptors diminished the severity of hyperosmolar-induced DO. In comparison with naïve animals the increased frequency of voiding with no significant effect on intravesical voiding pressure profile was observed as a result of the blockage of CB1 and CB2 receptors. These results demonstrate that hyperosmolar-induced DO is mediated by CB1 and CB2 receptors. Therefore, the cannabinoid pathway could potentially be a target for the treatment of urinary bladder dysfunction.

Impact of overactive bladder on quality of life and resource use: results from Korean Burden of Incontinence Study (KOBIS).

BACKGROUND: To evaluate the impact of overactive bladder (OAB) on quality of life (QOL), resource use and productivity loss in patients recruited from six hospitals in Korea. METHODS: This cross-sectional survey recruited 625 OAB patients between July to December 2013. Patients were categorised into four groups based on the average number of urinary incontinence (UI) episodes over the past three days (0, 1, 2-3 and ≥4 UI/day). QOL was measured using the Incontinence-Specific Quality of Life Instrument (I-QOL), the Overactive Bladder Questionnaire (OAB-q), and a generic health-related utility instrument (EQ-5D). Information on hospital and clinic visit frequency, and continence pads use were also collected. Work productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire. Between group differences were assessed using ANOVA. Multivariable regression analyses were performed to examine the independent effects of OAB symptoms on QOL. RESULTS: Severity of UI showed a significant linear relationship with QOL, with clinically meaningful differences between each UI severity category. Compared to the dry category, patients in the most severe category (≥4 UI/day) had significantly lower I-QOL scores (69.8 vs 42.6; p < 0.0001), greater symptom bother on the OAB-q (30.4 vs 64.6; p < 0.0001), and poorer EQ-5D utility (0.848 vs 0.742; p < 0.001). Multivariable analyses showed that UI severity, frequency, urgency, and nocturia are independently associated with poorer QOL. Incontinence severity is also significantly associated with cost of incontinence pads (p < 0.0001), and a greater interference with work and regular activities (p = 0.001), however, no significant difference in hospital and clinic visits were observed. CONCLUSION: Severity of UI is a key contributor to the disease burden of OAB in Korean patients, even after taking into account the impact of other symptoms associated with OAB.