Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder.
Ontology highlight
ABSTRACT: Aim
To characterize purinergic signaling in overactive bladder (OAB).Methods
Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB.Results
P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively).Conclusions
The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.
SUBMITTER: Firouzmand S
PROVIDER: S-EPMC8164356 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveTo assess change in overactive bladder (OAB) symptoms up to 5 years after surgery and to identify associated predictors of change from baseline.MethodsThis is a secondary analysis of data from three multicenter urinary incontinence (UI) surgical trials of women with stress-predominant mixed UI assigned to Burch colposuspension, autologous fascial sling, or retropubic or transobturator midurethral slings. The primary outcome was improvement of 70% or greater from baseline in symptoms measured by the Urinary Distress Inventory-Irritative subscale. Surgical groups were compared within respective trials. Generalized linear models were fit using 1-year and up to 5-year data.ResultsSignificant improvements in Urinary Distress Inventory-Irritative scores were reported by each surgical group 1 year after surgery (P<.001). Most women (50-71%) reported improvement in OAB symptoms. Improvements were similar between midurethral sling groups at 1 year (65.5% compared with 70.7%, P=.32; odds ratio [OR] 0.83, 95% confidence interval [CI] 0.57-1.20 for retropubic compared with transobturator sling) and throughout the 5-year follow-up period. More women reported OAB symptom improvement after Burch compared with pubovaginal sling (67.9% compared with 56.6%, P=.01; OR 1.59, 95% CI 1.10-2.31 for Burch compared with sling); this group difference at 1 year persisted throughout the 5-year follow-up. At 1-year, 50.0-64.3% of patients reported 70% greater improvement in UI. This proportion declined to 36.5-54.1% at 5 years (P<.001). Preoperative use of anticholinergics and urodynamic parameters was not predictive of OAB symptom change after surgery.ConclusionMost women with stress-predominant mixed UI experienced significant improvement in OAB symptoms after incontinence surgery although this initial improvement diminished over time. Obesity blunted symptom improvement.Level of evidenceII.
| S-EPMC4526119 | biostudies-literature
Project description:AIMS:The primary aim is to provide detailed rationale and methodology for the development and implementation of a perioperative behavioral/pelvic floor exercise research protocol for women who self-chose surgical intervention and who may or may not have been offered behavioral treatments initially. This protocol is part of the ESTEEM trial (Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence Trial) which was designed to determine the effect of a combined surgical and perioperative behavioral/pelvic floor exercise intervention versus surgery alone on improving mixed urinary incontinence (MUI) and overactive bladder (OAB) symptoms. METHODS:As part of a multi-site, prospective, randomized trial of women with MUI electing midurethral sling (MUS) surgical treatment, participants were randomized to a standardized perioperative behavioral/pelvic floor exercise intervention?+?MUS versus MUS alone. The specific behavioral intervention included: education on voiding habits, pelvic floor muscle training (PFMT), bladder training (BT), strategies to control urgency and reduce/prevent urinary symptoms, and monitoring/promoting adherence to behavioral recommendations. To ensure consistency across all eight research sites in the pelvic floor disorders network (PFDN), selective behavioral treatments sessions were audiotaped and audited for protocol adherence. RESULTS:The behavioral intervention protocol includes individualization of interventions using an algorithm based on pelvic floor muscle (PFM) assessment, participant symptoms, and findings from the study visits. We present, here, the specific perioperative behavioral/pelvic floor exercise interventions administered by study interventionists. CONCLUSIONS:This paper details a perioperative behavioral/pelvic floor exercise intervention research study protocol developed for women undergoing surgery for MUI.
| S-EPMC5907803 | biostudies-literature
Project description:ObjectiveTo investigate the relationship between sleep disturbance, fatigue, and urinary incontinence (UI) and overactive bladder (OAB) symptoms among patients with OAB.MethodsPatients who were diagnosed with OAB and age-matched control subjects without OAB were enrolled. Sleep disturbance and fatigue symptoms were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) short forms. UI and OAB symptoms were assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI), the International Consultation on Incontinence Questionnaire-Overactive Bladder (ICIQ-OAB), the Overactive Bladder Questionnaire (OAB-q), the Urogenital Distress Inventory Short Form (UDI-6), and the Incontinence Impact Questionnaire Short Form (IIQ-7). Psychosocial health (depression, anxiety, and perceived stress level) was also assessed.ResultsPatients with OAB reported a significantly greater sleep disturbance compared with controls (PROMIS 8b T-scores: 54.3 ± 10.3 vs 43.8 ± 9.2). Patients with OAB also reported a significantly greater fatigue compared with controls (PROMIS 7a T-scores: 54.7 ± 9.6 vs 46.0 ± 6.4). After adjusting for nocturia, the differences in sleep disturbance between OAB and controls became insignificant (P = .21), whereas the differences in fatigue between OAB and controls remained significant (P = .014). Among patients with OAB, there were positive correlations between sleep disturbance and the severity of OAB symptoms (ICIQ-OAB), poorer health-related quality of life (OAB-q QOL), the severity of UI symptoms (ICIQ-UI), greater incontinence impact (IIQ-7), and urinary bother (UDI-6). Positive correlations were also observed between fatigue and worse UI and OAB symptoms and quality of life. Both sleep disturbance and fatigue were associated with poor psychosocial health (depression, anxiety, and higher stress level) among patients with OAB.ConclusionSleep disturbance and fatigue are present in substantial percentages of patients with OAB. Among patients with OAB, sleep disturbance and fatigue were associated with more severe UI and OAB symptoms, worse health-related quality of life, and poorer psychosocial health.
| S-EPMC5669629 | biostudies-literature
Project description:The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder (OAB) has been measured by population-based investigations in many parts of the world. However, data are lacking for Eastern Europe, and there has not been any large population-representative study in any country of this region. Therefore, the aim of this study was to evaluate the prevalence and associated bother of LUTS and OAB in a population-representative sample of persons aged???40 years in Poland. This investigation was conducted as a computer-assisted telephone interview. The survey sample was stratified by age, sex, and place of residence to reflect the entire Polish population. LUTS and OAB were assessed by a standardized protocol based on the International Continence Society definitions and validated questionnaires. Of 6005 participants, 57% were women, and the mean age (range) was 60.7 (40-93) years. The prevalence of LUTS was 69.8% (men 66.2%; women 72.6%). There was no difference in prevalence between urban and rural areas. LUTS were often bothersome among men and women, but women were more likely to be bothered compared with men. There were also statistically significant correlations between the frequency and the bother intensity of each of the LUTS. The prevalence of OAB was higher in women (39.5%) than in men (26.8%), and OAB increased with age. Lastly, LUTS had detrimental effects on the quality of life because one third of the participants had concerns about their urinary-specific quality of life. This investigation was the first nationwide, population-representative epidemiological study of LUTS and OAB in an Eastern-European country. LUTS were highly prevalent, often bothersome, and had negative effects on the quality of life of men and women aged???40 years. Our findings are comparable with other epidemiologic studies of LUTS and OAB conducted in different regions of the world.Trial registration: NCT04121936.
| S-EPMC7666180 | biostudies-literature
Project description:The aim of this study was to measure, at the population level, the prevalence, bother, and treatment-related behavior for lower urinary tract symptoms (LUTS) and overactive bladder syndrome (OAB) in a large cohort of cardiology patients. This report is a further analysis of data from LUTS POLAND, a computer-assisted telephone survey that reflected the entire Polish population, stratified by age, sex, and place of residence. LUTS and OAB were assessed by a standardized protocol, the International Continence Society definitions, and validated questionnaires. In addition, all participants provided information regarding their behavior as it related to LUTS treatment. Overall, 6005 participants completed interviews, and 1835 (30.6%) had received treatment by cardiologists. The prevalence of LUTS was 73.3% for cardiology participants compared with 57.0% for respondents who were not treated by cardiologists (p < 0.001). There were no differences between men and women in LUTS prevalence for cardiology patients. Nocturia was the most prevalent LUTS. LUTS were often bothersome, and storage symptoms were more bothersome than voiding or postmicturition symptoms. The prevalence of OAB syndrome was 50.7% in cardiology patients, higher than in noncardiology participants (36.6%, p < 0.001), and more women were affected than men. Only one-third of cardiology patients who reported LUTS were seeking treatment for LUTS, and most of them received treatment. There were no differences between persons living in urban and rural areas. LUTS and OAB were highly prevalent among cardiology patients. Although LUTS were often bothersome in this unique population, we found that the seeking of treatment for LUTS was minimal. These results highlight the need for cooperation between cardiologists and urologists.
| S-EPMC7766299 | biostudies-literature
Project description:BackgroundA reliable reference of population-based parameters for lower urinary tract symptoms (LUTS) and overactive bladder (OAB) is lacking for the elderly. Thus, the objective of this study was to estimate the prevalence, bother, effect on quality of life, and treatment-related behavior for LUTS and OAB in a large population-level cohort of Polish adults aged ≥ 65 years.MethodsWe used data from the telephone LUTS POLAND survey. Respondents were categorized by sex, age, and residence. All LUTS and OAB were assessed with validated questionnaires and a standard protocol based on the International Continence Society definitions.ResultsThe mean (standard deviation) age of 2402 participants (60.4% women) was 72.5 (6.7) years. The prevalence of LUTS was 79.5% (men: 76.6%; women: 81.4%), and the prevalence of OAB was 51.4% (men: 49.4%; women: 52.8%). The prevalence of both conditions increased with age. The most prevalent symptom was nocturia. LUTS and OAB were often bothersome, and almost half of participants who reported LUTS or OAB had decreased quality of life related to their urinary functioning. Nevertheless, only one third of participants sought treatment for their bladder problems, and most of these participants received treatment. We did not observe differences between urban and rural areas in all analyzed population-level parameters.ConclusionsLUTS and OAB were prevalent conditions with significant bother and negative effects on quality of life among Polish adults aged ≥ 65 years. Nevertheless, most affected respondents had not sought treatment. Thus, for older persons, there is a need to increase public awareness about LUTS and OAB, and the negative effects of LUTS and OAB on healthy aging. In addition, greater government and healthcare system resources are needed to better manage LUTS and OAB in older patients.
| S-EPMC10142045 | biostudies-literature
Project description:Although it is known that changes in bacterial components of the urinary microbiome are associated with overactive bladder (OAB), the specific role of viruses is still insufficiently investigated. The aim of the present study is to evaluate the role of urinary viruses in woman with OAB, and analyze the potential relationship between viruses, bacteria and disease. Catheterized urine samples were collected from 55 women with OAB and 18 control individuals. OAB patients fulfilling the following criteria were considered eligible for this study: female, 18 years of age or older; presented with classic OAB symptoms defined by the International Continence Society; and OAB Symptom Score (OABSS) total score ≥ 3 points and question 3 (urgency) score ≥ 2 points. Based on results of metagenomic next-generation sequencing (mNGS), all participants were divided into virus-infected and virus-uninfected groups for analysis. The results of mNGS showed that the diversity of the OAB group was lower than that of the control group when focused on bacterial sequences, which was consistent with our previous study. According to the questionnaire filled out by the patients, OABSS and 8-item OAB questionnaire, female OAB patients who had viruses detected in their urine had more severe symptoms. In parallel, John Cunningham virus (mainly subtype 7 and subtype 2) was the most frequently detected virus in urine. Correlation analysis indicated that risk factors for virus infection in OAB patients include age, habit of holding urine and pelvic surgery history. Given our preliminary data, viral infection can aggravate OAB severity and affect the composition of bacterial. Further research is required to explain how viral infections can aggravate OAB patient symptoms and cause bacterial changes.
| S-EPMC9537457 | biostudies-literature
Project description:Objectives: Emerging evidence indicates that alterations to the urinary microbiome are related to lower urinary tract symptoms. Overactive bladder (OAB) is a common disorder with complex etiologies and usually accompanied by psychological diseases. More information concerning the urinary microbiome and psychological factors in OAB is required. The aim of this study was to characterize the female urinary microbiome associated with OAB and investigate the relationships between urinary microbiome and psychological factors. Methods: Thirty women with OAB and 25 asymptomatic controls were recruited and asked to finish the Overactive Bladder Symptom Score, Self-Rating Anxiety Scale and Self-Rating Depression Scale. Urine specimens were collected by transurethral catheterization and processed for 16S rRNA gene sequencing using Illumina MiSeq. Sequencing reads were processed using QIIME. LEfSe revealed significant differences in bacterial genera between controls and OAB patients. The relationships between the diversity of the urinary microbiome and psychological scores were identified by Pearson's correlation coefficient. Results: We found that bacterial diversity (Simpson index) and richness (Chao1) were lower in OAB samples compared to controls (P both = 0.038). OAB and control bacterial communities were significantly different (based on weighted UniFrac distance metric, R = 0.064, P = 0.037). LEfSe demonstrated that 7 genera were increased (e.g., Proteus and Aerococcus) and 13 were reduced (e.g., Lactobacillus and Prevotella) in OAB group compared to controls. There were negative correlations between scores on Self-Rating Depression Scale and both richness (Chao1, r = -0.458, P = 0.011) and diversity (Shannon index, r = -0.516, P = 0.003) of urinary microbiome in OAB group. Some bacterial genera of OAB women with anxiety or depression were significantly different from those without. Conclusions: The aberrant urinary microbiome with decreased diversity and richness may have strong implications in pathogenesis and treatment of OAB. Psychological conditions were correlated with characteristics of urinary microbiome in women with OAB. Further research is needed to understand the connection between central nervous system and urinary microbiome.
| S-EPMC5712163 | biostudies-literature
Project description:IntroductionA prespecified pooled analysis of two placebo-controlled, phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder (OAB) patients with urinary incontinence (UI).MethodsPatients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo, sparing the trigone. Change from baseline at week 12 in UI episodes/day, proportion of patients reporting a positive response ('greatly improved' or 'improved') on the treatment benefit scale (TBS), micturition and urgency were evaluated by number of prior anticholinergics (1, 2 or ≥ 3) and reason for their discontinuation (insufficient efficacy or side effects). Adverse events (AE) were assessed.ResultsPatients had taken an average of 2.4 anticholinergics before study enrolment. OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo, regardless of the number of prior anticholinergics (-2.82 vs. -1.52 for one prior anticholinergic; -2.58 vs. -0.58 for two prior anticholinergics; and -2.92 vs. -0.73 for three or more prior anticholinergics; all p < 0.001). The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo (69.0% vs. 37.2% for one prior anticholinergic; 58.8% vs. 24.8% for two prior anticholinergics and 56.4% vs. 22.5% for three or more prior anticholinergics; all p < 0.001). Similar results were observed regardless of the reason for discontinuation. OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups. AEs were well tolerated, with a comparable incidence in all groups.ConclusionIn patients with symptoms of OAB who were inadequately managed by one or more anticholinergics, onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB. ClinicalTrials.gov: NCT00910845, NCT00910520.
| S-EPMC4282287 | biostudies-literature
Project description:PurposeAwakening from sleep to urinate is the hallmark of nocturia, a condition that impacts several facets of health related quality of life and for which current therapy is suboptimal. Given the paucity of prospective data on antimuscarinics for the management of nocturia, we investigated the efficacy and safety of flexible dose fesoterodine for the treatment of nocturnal urgency in subjects with nocturia and overactive bladder.Materials and methodsSubjects with 2 to 8 nocturnal urgency episodes per 24 hours began a 2-week, single-blind, placebo run-in followed by 1:1 randomization to 12 weeks of double-blind treatment with fesoterodine (4 mg daily for 4 weeks with an optional increase to 8 mg) or placebo using predefined criteria for nocturnal urgency episodes, nocturnal urine volume voided and total 24-hour urine volume voided. The primary end point was change from baseline to week 12 in the mean number of micturition related nocturnal urgency episodes per 24 hours.ResultsOverall 963 subjects were randomized from 2,990 screened, and 82% of subjects treated with fesoterodine and 84% of those treated with placebo completed the study. Significant improvements in the primary end point (-1.28 vs -1.07), in nocturnal micturitions per 24 hours (-1.02 vs -0.85) and in nocturnal frequency urgency sum (-4.01 vs -3.42) were observed with fesoterodine vs placebo (all p ≤0.01). Health related quality of life measures (overactive bladder questionnaire Symptom Bother -20.1 vs -16.5, sleep 22.3 vs 19.9 and other domains; all p <0.05) were improved with fesoterodine.ConclusionsTo our knowledge this is the first prospective study to assess antimuscarinic efficacy for reducing nocturnal urgency. Flexible dose fesoterodine significantly reduced nocturnal urgency episodes vs placebo in subjects with overactive bladder.
| S-EPMC3679189 | biostudies-literature