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Impaired contractility of the circular striated urethral sphincter muscle may contribute to stress urinary incontinence in female zucker fatty rats.

ABSTRACT: Obesity has been an independent risk factor for female stress urinary incontinence (SUI), the mechanism of this association remains unknown. The aim of this study is to validate the hypothesis that urethral dysfunction is a possible contributor to SUI in obese women.Ten Zucker Fatty (ZF) (ZUC-Leprfa 185) and 10 Zucker Lean (ZL) (ZUC-Leprfa 186) female rats at 12-week-old were used in this experiment. The urethral sphincter rings were harvested from the bladder neck through to the most proximal 2/3 regions. In the organ bath study, single pulses of electrical field stimulation (EFS) were applied. For the fatiguing stimulation, repeated multi-pulse EFS with 70 mA were applied at frequency of 5 Hz for 5 min. Caffeine-containing Krebs' solution was administrated to contract the urethra until the contraction began to reach a plateau for 10 min. We performed immunofluorescence staining of the urethra after the experiment was finished.Compared to ZL controls, ZF rats had significantly impaired muscle contractile activity (MCA) (P < 0.05). Also, ZF rats presented early fatiguing of MCA and had a significantly greater percentage of MCA decline from baseline in the fatiguing test (37.7% vs 25.6%, P < 0.05). The plateau of maximal MCA induced by caffeine in ZF rats was significantly lower than ZL controls (0.22 vs 0.36, P < 0.05).This novel study showed that obese female rats had significantly impaired contractile properties of striated urethral sphincter, suggesting urethral dysfunction could be an important contributor to SUI in obesity.

SUBMITTER: Lee YC

PROVIDER: S-EPMC5546299 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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TAS-303 effects on urethral sphincter function in women with stress urinary incontinence: phase I study.

Project description:Introduction and hypothesisTAS-303, which selectively inhibits noradrenaline reuptake, was developed for treating stress urinary incontinence (SUI). The proximal urethra mainly comprises smooth muscle fibers in which ?1 adrenergic receptors are abundant. This study was conducted to evaluate the effect of TAS-303 on urethral function and its safety profile in female patients with SUI.MethodsIn total, 16 women (age, 20-64 years) with SUI and?>?5.0 g of leakage in the 1-h pad test at screening were randomized and administered the assigned treatment in a double-blind manner. The primary end point was change in the maximal urethral closure pressure (MUCP) at 6 h post-dose. The secondary end point was change in the urethral closure pressure of the entire urethra and each urethral region (proximal, middle, and distal) at 6 h post-dose. The results were analyzed using a t-test.ResultsThe mean change ± standard deviation in MUCP at 6 h post-dose was 3.473?±?12.154 cmH2O for TAS-303 and 2.615?±?9.794 cmH2O for placebo (between-group difference: 0.858 cmH2O, P?=?0.8047). The mean changes ± standard deviation in urethral closure pressure of the proximal urethra at 6 h after the administration of TAS-303 18 mg and placebo were 3.863?±?10.941 and 1.634?±?12.093, respectively (between-group difference: 2.229 cmH2O, P?=?0.5976).ConclusionsNo significant difference in MUCP and urethral closure pressure was found between TAS-303 and placebo. However, the change in the proximal urethral closure pressure with TAS-303 was larger than that with placebo. This suggests that TAS-303 has pharmacological effects on urethral sphincteric function.

| S-EPMC7902327 | biostudies-literature

Therapeutic Efficacy of Urethral Sphincter Injections of Platelet-Rich Plasma for the Treatment of Stress Urinary Incontinence due to Intrinsic Sphincter Deficiency: A Proof-of-Concept Clinical Trial.

Project description:PurposeThe aim of this study was to investigate the efficacy of autologous platelet-rich plasma (PRP) in the treatment of stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD) refractory to medical treatment.MethodsThirty-five patients with SUI due to urodynamically proven ISD were prospectively enrolled. Five milliliters of PRP (2.5-5 times the platelet concentration in peripheral blood) was injected into the external sphincter at 5 sites; all patients received 4 injections at monthly intervals. The primary end-point was the change in SUI severity as assessed by a visual analogue scale (VAS of SUI). The secondary-endpoints were the Global Response Assessment score and changes in urodynamic parameters from baseline to 3 months after treatment.ResultsThe mean age of patients was 68.7±12 years; the median duration of SUI was 4 years. Five patients had neurogenic SUI, while 30 had nonneurogenic SUI (21 with postprostatectomy incontinence, 6 with previous radical cystectomy, and 3 with other etiologies). Complete dryness was achieved in 7 patients (20.0%) while moderate improvement was observed in 14 (40.0%). The mean VAS of SUI score decreased significantly from 6.57±1.89 to 3.77±2.41 after treatment. The abdominal leak point pressure (ALPP) increased significantly from 98.3±55.8 to 157.3±79.3 cm H2O. There was no increase of ALPP in neurogenic SUI and less increase of ALPP in patients with failed treatment outcomes. No perioperative adverse events or severe complications occurred.ConclusionUrethral PRP injection is safe and effective in increasing urethral resistance and improving SUI. PRP could be an alternative treatment modality for male and female patients with moderate SUI due to nonneurogenic causes.

| S-EPMC8022168 | biostudies-literature

Mid-urethral sling operations for stress urinary incontinence in women.

Project description: Not available

| S-EPMC6483329 | biostudies-literature

Urethral failure is a critical factor in female urinary incontinence. Now what?

Project description: Not available

| S-EPMC8892071 | biostudies-literature

Does Medicaid cover artificial urinary sphincter and male urethral sling surgery?-a state-by-state analysis.

Project description:BackgroundInformation regarding the Medicaid coverage of artificial urinary sphincter (AUS) and male suburethral slings (MS) placement in the United States (US) is not readily available. In this manuscript, we seek to elucidate the state-by-state Medicaid coverage of these two procedures in the US.MethodsState Medicaid websites were utilized to access publicly available physician fee schedules for the calendar year 2020. Fee schedules were searched for current procedural terminology (CPT) codes. CPT codes representing insertion of tandem cuff, insertion of AUS, removal of AUS, removal and replacement AUS, sling operation for correction of male stress urinary incontinence (SUI), and removal or revision of sling for male SUI were utilized. Data were recorded by the procedure for each device, including the coverage status and physician fees.ResultsOf the 50 US states analyzed, 49 publish publicly accessible physician fee schedules. All 49 of these states reported coverage for removal with and without revision of the AUS, and 48 states reported coverage for insertion of an AUS, and insertion of a tandem cuff. The median reimbursement for each AUS related procedure was $624.00 ($181.84-$10,960.90) for tandem cuff, $665.54 ($199.89-$11,949.86) for AUS insertion, $528.03 ($146.90-$1,893.12) for AUS removal, and $630.29 ($208.55-$11,586.74) for AUS revision. All 49 states reported coverage for placement of MS, and 48 states reported coverage for removal or revision of MS. The median reimbursement was $652.57 ($198.00-$5,237.35) for MS placement and $554.47 ($104.27-$2,288.93) for MS revision.ConclusionsAUS and MS procedures in the Medicaid population are covered by nearly all states. Therefore, surgical treatment of SUI may be offered to Medicaid patients in most states without reimbursement concerns.

| S-EPMC10005999 | biostudies-literature

The effects of microenergy acoustic pulses on animal model of obesity-associated stress urinary incontinence. Part 2: In situ activation of pelvic floor and urethral striated muscle progenitor cells.

Project description:AIM:To investigate the possibility and mechanism of microenergy acoustic pulses (MAP) for activating tissue resident stem/progenitor cells within pelvic and urethral muscle and possible mechanism. METHODS:The female Zucker Lean and Zucker Fatty rats were randomly divided into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. MAP was applied at 0.033?mJ/mm2 , 3?Hz for 500 pulses, and the urethra and pelvic floor muscles of each rat was then harvested for cell isolation and flow cytometry assay. Freshly isolated cells were analyzed by flow cytometry for Pax-7, Int-7?, H3P, and EdU expression. Meanwhile, pelvic floor muscle-derived stem cells (MDSCs) were harvested through magnetic-activated cell sorting, MAP was then applied to MDSCs to assess the mechanism of stem cell activation. RESULTS:Obesity reduced EdU-label-retaining cells and satellite cells in both pelvic floor muscle and urethra, while MAP activated those cells and enhanced cell proliferation, which promoted regeneration of striated muscle cells of the pelvic floor and urethral sphincter. Activation of focal adhesion kinase (FAK)/AMP-activated protein kinase (AMPK) /Wnt/?-catenin signaling pathways by MAP is the potential mechanism. CONCLUSIONS:MAP treatment activated tissue resident stem cells within pelvic floor and urethral muscle in situ via activating FAK-AMPK and Wnt/?-catenin signaling pathway.

| S-EPMC6801020 | biostudies-literature

Liquid crystal elastomer based dynamic device for urethral support: Potential treatment for stress urinary incontinence.

Project description:Stress urinary incontinence (SUI) is characterized by the involuntary loss of urine due to increased intra-abdominal pressure during coughing, sneezing, or exercising. SUI affects 20-40% of the female population and is exacerbated by aging. Severe SUI is commonly treated with surgical implantation of an autologous or a synthetic sling underneath the urethra for support. These slings, however, are static, and their tension cannot be non-invasively adjusted, if needed, after implantation. This study reports the fabrication of a novel device based on liquid crystal elastomers (LCEs) capable of changing shape in response to temperature increase induced by transcutaneous IR light. The shape change of the LCE-based device was characterized in a scar tissue phantom model. An in vitro urinary tract model was designed to study the efficacy of the LCE-based device to support continence and adjust sling tension with IR illumination. Finally, the device was acutely implanted and tested for induced tension changes in female multiparous New Zealand white rabbits. The LCE device achieved 5.6% ± 1.1% actuation when embedded in an agar gel with an elastic modulus of 100 kPa. The corresponding device temperature was 44.9 °C ± 0.4 °C, and the surrounding agar temperature stayed at 42.1 °C ± 0.4 °C. Leaking time in the in vitro urinary tract model significantly decreased (p < 0.0001) when an LCE-based cuff was sutured around the model urethra from 5.2min ± 1min to 2min ±0.5min when the cuff was illuminated with IR light. Normalized leak point force (LPF) increased significantly (p = 0.01) with the implantation of an LCE-CB cuff around the bladder neck of multiparous rabbits. It decreased significantly (p = 0.023) when the device was actuated via IR light illumination. These results demonstrate that LCE material could be used to fabricate a dynamic device for treating SUI in women.

| S-EPMC9772118 | biostudies-literature

Artificial Urinary Sphincter Is Better Than Slings for Moderate Male Stress Urinary Incontinence With Acceptable Complication Rate: A Systematic Review and Meta-Analysis.

Project description:BackgroundThis meta-analysis aimed to compare the efficacy of artificial urinary sphincter (AUS) and slings for the treatment of moderate male stress urinary incontinence (SUI) based on existing data.MethodsThe study was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched the widely acknowledged database including PubMed, Embase (Ovid version), Medline (Ovid version), and Cochrane Central Register of Controlled Trials (till February 2021). Male patients with moderate SUI who underwent AUS or slings procedure over 18 years old and had been monitored with a mean follow-up time of at least 12 months were included. The primary outcome was success rate defined as daily pad use with 0-1 pad/d postoperatively. Articles with congruent outcomes were suitable for inclusion. The secondary outcome included complication rate of infection, erosion, acute urinary retention, and surgical revision.ResultsFive studies with a total of 509 patients (295 for slings and 214 for AUS) were recruited. The success rate was higher in AUS with an odds ratio (OR) = 0.57 (95% CI: 0.36-0.90). As for the overall complication rate, no significant difference was discovered between slings and AUS groups (OR = 1.06, 95% CI: 0.58-1.92, P = 0.86).ConclusionTo conclude, AUS was better than slings for moderate male SUI treatment according to daily pad use with an acceptable complication rate. The slings also had clinical value and were options when aging male patients were AUS naive and refused inserted mechanical devices. High-quality pieces of evidence are needed to confirm the efficacy of AUS and slings in moderate male SUI.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=271203, identifier: CRD42021271203.

| S-EPMC8863861 | biostudies-literature

External urethral sphincter pressure measurement: an accurate method for the diagnosis of detrusor external sphincter dyssynergia?

Project description:BackgroundCombined pelvic floor electromyography (EMG) and videocystourethrography (VCUG) during urodynamic investigation are the most acceptable and widely agreed methods for diagnosing detrusor external sphincter dyssynergia (DESD). Theoretically, external urethral sphincter pressure (EUSP) measurement would provide enough information for the diagnosis of DESD and could simplify the urodynamic investigation replacing combined pelvic floor EMG and VCUG. Thus, we evaluated the diagnostic accuracy of EUSP measurement for DESD. PATIENTS #ENTITYSTARTX00026;MethodsA consecutive series of 72 patients (36 women, 36 men) with neurogenic lower urinary tract dysfunction able to void spontaneously was prospectively evaluated at a single university spinal cord injury center. Diagnosis of DESD using EUSP measurement (index test) versus combined pelvic floor EMG and VCUG (reference standard) was assessed according to the recommendations of the Standards for Reporting of Diagnostic Accuracy Initiative.ResultsUsing EUSP measurement (index test) and combined pelvic floor EMG and VCUR (reference standard), DESD was diagnosed in 10 (14%) and in 41 (57%) patients, respectively. More than half of the patients presented discordant diagnosis between the index test and the reference standard. Among 41 patients with DESD diagnosed by combined pelvic floor EMG and VCUR, EUSP measurement identified only 6 patients. EUSP measurement had a sensitivity of 15% (95% CI 5%-25%), specificity of 87% (95% CI 76%-98%), positive predictive value of 60% (95% CI 30%-90%), and negative predictive value of 56% (95% CI 44%-68%) for the diagnosis of DESD.ConclusionsFor diagnosis of DESD, EUSP measurement is inaccurate and cannot replace combined pelvic floor EMG and VCUR.

| S-EPMC3365101 | biostudies-literature

Voluntary urination control by brainstem neurons that relax the urethral sphincter.

Project description:Voluntary urination ensures that waste is eliminated when safe and socially appropriate, even without a pressing urge. Uncontrolled urination, or incontinence, is a common problem with few treatment options. Normal urine release requires a small region in the brainstem known as Barrington's nucleus (Bar), but specific neurons that relax the urethral sphincter and enable urine flow are unknown. Here we identify a small subset of Bar neurons that control the urethral sphincter in mice. These excitatory neurons express estrogen receptor 1 (BarESR1), project to sphincter-relaxing interneurons in the spinal cord and are active during natural urination. Optogenetic stimulation of BarESR1 neurons rapidly initiates sphincter bursting and efficient voiding in anesthetized and behaving animals. Conversely, optogenetic and chemogenetic inhibition reveals their necessity in motivated urination behavior. The identification of these cells provides an expanded model for the control of urination and its dysfunction.

| S-EPMC6119086 | biostudies-literature

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