Urethral Sphincter Muscle Research Articles

Noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques

Dysfunction of the lower urinary tract (LUT) is prevalent in neurological disorders, including multiple sclerosis, stroke, spinal cord injury and neurodegenerative conditions. Common symptoms include urgency, incontinence, and urinary retention. Recent advances in neuromodulation have resulted in improved treatments for overactive bladder symptoms of urgency, frequency, and nocturia. However, there are presently no treatments available for the induction of voiding to overcome urinary retention. We demonstrate that transcutaneous spinal cord stimulation (TSCS), a non-invasive intervention, applied over the thoracolumbar spine in neurologically intact rhesus macaques can activate the LUT, including activation of the bladder detrusor muscle, the urethral sphincter and pelvic floor muscles. Urodynamic studies show improved voiding efficiency and decreased post-voiding residual volumes in the bladder, while maintaining coordinated activity in the detrusor and sphincter with physiologic detrusor peak pressure, contraction duration, and urine flow rate remaining unchanged. We conclude that TSCS may represent a novel approach to activate the LUT and enable voiding in select neurological conditions.

Activation of the spinal neuronal network responsible for visceral control during locomotion

It has been established that stepping of the decerebrate cat was accompanied by involvement of the urinary system: external urethral sphincter (EUS) and detrusor muscle activation, as well as the corresponding increase of the intravesical pressure. Detrusor and EUS evoked EMG activity matched the limbs locomotor movements. Immunohistochemical labeling of the immediate early gene c-fos expression was used to reveal the neural mechanisms of such somatovisceral interconnection within the sacral neural pathways. Study showed that two locomotor modes (forward and backward walking) had significantly different kinematic features. Combining the different immunohistochemical methods, we found that many c-fos-immunopositive nuclei were localized within several visceral areas of the S2 spinal segment which matched the sacral parasympathetic nucleus and dorsal gray commissure. Cats stepping backward had 4-fold more c-fos-immunopositive nuclei within the ventrolateral part of the sacral parasympathetic nucleus apparently correspondent to the “lateral band” contained cells controlling bladder function. The present work provides the direct evidences of visceral neurons activation depending on the specific of locomotor pattern and confirms the somatovisceral integration carrying out on the spinal cord level.

PENGARUH PEMBERIAN KOMBINASI KEGEL EXERCISE DAN BRIDGING EXERCISE TERHADAP PERUBAHAN FREKUENSI INKONTINENSIA URIN PADA LANJUT USIA DI YAYASAN BATARA HATI MULIA GOWA

Lansia merupakan suatu tahap lanjut dari proses kehidupan yang ditandai dengan penurunan kemampuan tubuh. Sehingga banyak terjadi perubahan pada anatomis dan fisologis tubuh lansia diantaranya perubahan neurologi, musculoskeletal dan kandung kemih. Hal ini berdampak pada kelemahan otot pelvic floor yang menyebabkan terjadinya inkontinensia urin karena tidak adekuatnya otot sfingter uretra dalam mencegah kebocoran urin. Penangan inkontinensia urin ini dilakukan dengan memberikan latihan melalui pendekatan penguatan otot pelvic floor secara langsung dan otot core secara keseluruhan.Penelitian ini bertujuan untuk mengetahui pengaruh kombinasi kegel exercise dan bridging excerise terhadap perubahan inkontinensia urin pada lansia. Penelitian ini merupakan penelitian pre-experimental design, dengan pendekatan penelitian one group pretest-posttest design. Populasi penelitian ini adalah seluruh lansia yang ada di Yayasan Batara Hati Mulia, Gowa. Teknik pengambilan sampel dalam penelitian ini adalah purposive sampling dengan jumlah sampel 13 orang.Pengumpulan data dilakukan dengan cara pengambilan data primer melalui wawancara dan didasarkan pada skala ordinal frekuensi inkontinensia urin. Penelitian ini dilakukan selama 6 minggu dengan 18 kali pemberian latihan. Uji statistik yang digunakan adalah paired sample t test. Hasil analisis pre test dan post test memperlihatkan penurunan frekuensi inkontinensia urin dengan nilai p < 0,000. Hal tersebut menunjukkan bahwa kombinasi kegel exercise dan bridging exercise berpengaruh terhadap perubahan frekuensi inkontinensia urin pada lansia.
 

Intraoperative Triggered Electromyography Recordings from the External Urethral Sphincter Muscles During Spine Surgeries.

Introduction: Bowel and bladder function are at risk during tumor resection and other surgeries of the conus, cauda equina, and nerve roots. This study demonstrates the ability to acquire triggered electromyography (t-EMG) from the external urethral sphincter (EUS) muscles by utilizing a urethral catheter with an electrode attached.Methods: A retrospective analysis of neurophysiological monitoring data from two medical centers was performed. Seven intradural tumors and three tethered cord release surgeries that used urethral sphincter electrodes to record t-EMG were included in the analysis. The patients consisted of five females and five males with ages ranging from eight months to 67 years (median: 49 years). Our neuromonitoring paradigm included upper and lower extremity somatosensory evoked potentials (SSEPs) and transcranial electrical motor evoked potentials (TCeMEPs), as well as spontaneous and triggered electromyography (EMG) from the external anal sphincter (EAS), EUS muscles and lower extremity muscles bilaterally. A catheter with urethral electrodes attached was used for recording spontaneous electromyography (s-EMG), t-EMG, and TCeMEPs from the skeletal muscle of the EUS. Train of four (TOF) was also recorded from the abductor hallucis muscle as well for monitoring the level of muscle relaxant.Results: We were able to successfully record t-EMG responses from the EUS muscles in all patients (100%). It is worthy to note that only one patient presented preoperatively with bladder incontinence, urgency, and frequency. Almost immediately in the postoperative phase, the patient’s frequency and urgency improved, and the bladder function normalized within two weeks of having the tumor removed.Conclusions: In this small series, we were able to acquire t-EMG in 100% of patients when recorded from the EUS using a urethral catheter with electrodes built into it. T-EMGs can be attempted in surgeries that put the function of the pelvic floor at risk. More study is needed to establish better statistical methods, better modality efficacy, and a better understanding of intraoperative countermeasures that may be employed when an alert is encountered to prevent impending neurological sequelae.

Motor Evoked Potential Recordings from the Urethral Sphincter Muscles (USMEPs) during Spine Surgeries

ABSTRACTBowel and bladder function are at risk during tumor resection of the conus, cauda equina, and nerve roots. This study demonstrates the ability to acquire transcranial electrical motor evoked potentials (TCeMEPs) from the urethral sphincter muscles (USMEPs) by utilizing a urethral catheter with an embedded electrode. A retrospective analysis of intraoperative neurophysiological monitoring (IONM) data from nine intradural tumors, four tethered cord releases, and two spinal stenosis procedures was performed (n = 15). The cohort included seven females and eight males (median age: 38.91 years). A catheter with embedded urethral electrodes was used for recording TCeMEPs and spontaneous electromyograph (s-EMG) from the external urethral sphincter (EUS). USMEPs were obtained in 14 patients (93%). The reliability of TCeMEP from the external anal sphincter (EAS) was variable across all patients. In patient 7, the TCeMEP recordings from the urethral sphincter were not present before incision; however, following the resection of the tumor, the USMEP recordings were obtained and remained stable for the remainder of the procedure. Patient 7 had subsequent improvement in bladder function postoperatively. Patient 4 exhibited a 50% increase in the amplitude of the USMEP following tumor resection and exhibited improved bladder function as well postoperatively. In this small series, we were able to acquire consistent and reliable MEPs when recorded from the urethral sphincters. More study is needed to establish a better understanding of the value added by this modality. USMEPs can be attempted in surgeries that put the function of the pelvic floor at risk.

Age and multiparity related urethral sphincter muscle dysfunction in a rabbit model: Potential roles of TGF-β and Wnt-β catenin signaling pathways.

Prior studies demonstrate increased incidence of urinary incontinence (UI) in the geriatric population which affects their quality of life. Pathophysiology of UI in the geriatric population and the underlying molecular mechanisms are still unclear. To elucidate these mechanisms, we performed a pre-clinical study in a rabbit model and the objectives were to (i) determine the effect of aging as well as multiparity on urethral sphincter muscle thickness and urethral closing pressure (UCP); (ii) examine the role of fibrosis and atrophy; and (iii) elucidate the molecular pathways that mediate fibrosis and atrophy in the urethral tissue. New Zealand White female rabbits (n = 6 each; young 6-12 months and old over 30 months of age) were anesthetized and urethral muscle thickness and sphincter closure function were measured. Rabbits were then sacrificed and urethral tissues (bladder neck and mid-urethra) were collected to process for immunostaining as well as for molecular studies for markers for fibrosis (β-catenin which is an important mediator of Wnt signaling, Collagen-1, and TGF-β) and atrophy (MuRF-1). Our studies showed a significant decrease in the urethral sphincter muscle thickness and closure function with age. Age-related increase in protein and mRNA expression levels of fibrosis, as well as atrophy markers were observed in the bladder neck and mid-urethral tissues. Age and multiparity related increase in fibrosis and atrophy of urethral sphincter muscles may contribute to impaired urethral closure function seen in old animals.

Effect of a 5-HT2c receptor agonist on urethral closure mechanisms in female rats.

The serotonin (5-HT2c) receptor is known to be involved in the mechanism of urethral closure in a model of stress incontinence. Lorcaserin (Belviq®) has received Food and Drug Administration approval for the treatment of obesity. However, it is unclear whether this selective 5-HT2c receptor agonist enhances urethral closure in stress urinary incontinence (SUI) models. Therefore, we investigated whether lorcaserin could enhance urethral closure in female rats with vaginal distention (VD). Normal female rats and rats with stress incontinence induced by VD were tested. We evaluated the effect of a single dose of lorcaserin (0.03, 0.3, or 0.9 mg/kg with cumulative administration) on the urethral pressure amplitude during electrical stimulation (A-URE) and on the urethral baseline pressure (UBP). The manual compression-induced leak point pressure (LPP) was also measured. In VD rats, a single intravenous injection of lorcaserin (0.3 and 0.9 mg/kg) significantly increased both A-URE and LPP compared to saline (P < 0.05). In normal rats, intravenous lorcaserin (0.3 and 0.9 mg/kg) also significantly increased A-URE and LPP compared to saline (P < 0.05). The changes of A-URE and LPP, which are parameters of active urethral closure, were significantly larger in normal rats than in VD rats. We showed that lorcaserin can activate the external urethral sphincter and pelvic floor muscles, suggesting an influence on active closure mechanisms. 5-HT2c receptors agonists may have dual effects in patients with SUI, not only by reducing obesity but also by enhancing active urethral closure.

Effects of 7-difluoromethy-5, 4'-dimethoxygenistein on stress urinary incontinence model in rats and its mechanisms

To investigate the effects of 7-difluoromethy-5, 4'-dimethoxygenistein (DFMG) on stress urinary incontinence (SUI) model in Sprague Dawley (SD) rats and its possible mechanisms. Methods: SD rat model of SUI was established through simulating pregnancy, birth trauma and ovarian castration. The rats were divided into a normal control group, a SUI group, and a DFMG group at 10 or 20 mg/kg. They were treated with 10 mg/kg normal saline (NS), 10 mg/kg NS, 10 mg/kg DFMG and 20 mg/kg DFMG, respectively, via gastric gavage every other day. Maximal bladder capacity (MBC), leak point pressure (LPP), abdominal leak point pressure (ALPP), hematoxylin-eosin (HE) staining, and Masson staining were performed to detect the index for the model. MiR-26b and its down-stream gene phosphatase and tensin homolog deleted on chromosome 10 (PENT) mRNA in urethral sphincter muscles cells (USMCs) were analyzed by RT-PCR. The protein levels of PENT, phosphatidylinositol 3-kinase (PI3K), protein kinaseB (AKT), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome C(Cyt-c) and caspase-3 were examined by Western blot. The apoptotic rate of USMCs was determined by flow cytometry (FCM), and the proliferative rate of USMCs was examined by MTT assay. Results: The SD rat model of SUI was successfully established. HE staining and Masson staining showed that the pathological features of urethral sphincter were improved in the DFMG-treated groups compared with the SUI group. The urine dynamics indexes of model rats, such as MBC, LPP and ALPP, were improved (all P﹤0.05). The results of RT-PCR showed that the miR-26b mRNA was up-regulated (P﹤0.05) and PENT mRNA was down-regulated (P﹤0.05) in the DFMG-treated groups compared with the SUI group. Simultaneously, compared with the SUI group, the protein levels of PENT, Bax, Cyt-c and caspase-3 were down-regulated (all P﹤0.05) and the protein levels of PI3K, AKT and Bcl-2 protein were up-regulated (all P﹤0.05), accompanied by the decreased apoptotic rate of USMCs (P﹤0.05) and the increased proliferative rate of USMCs (P﹤0.05) in the DFMG-treated groups. Conclusion: The DFMG can significantly improve the symptoms of urinary dynamics, which might be related to the up-regulation of miR-26b expression and the regulation of PI3/AKT-Bcl-2/ Bax signaling pathways.

Exploration of male urethral sphincter complex using diffusion tensor imaging (DTI)-based fiber-tracking.

Urinary incontinence is a major clinical problem arising primarily from age-related degenerative changes to the sphincter muscles. However, the precise anatomy of the normal male sphincter muscles has yet to be established. Diffusion tensor imaging (DTI) may offer a unique insight into muscle microstructure and fiber architecture. To explore the anatomy of the urethral sphincter muscles pertinent to urinary continence function using DT-MRI. Prospective cohort study. Eleven normal male subjects (mean age: 25.4 years); two subjects were scanned in three separate sessions to assess reproducibility. 3T; using a diffusion-weighted spin echo planar sequence. DT parameters including fractional anisotropy (FA), primary (λ1 ), secondary (λ2 ), and tertiary (λ3 ) eigenvalues, Apparent diffusion coefficient and radial diffusivity were analyzed statistically, while tracked muscle fibers were assessed visually. Regional differences (sphincters and longitudinal muscle of the urethra) in the DTI indices were assessed by one-way analysis of variance. A Tukey post-hoc test was used to identify significant differences between muscle regions. Two sphincter muscles, one proximal near the base of the bladder, corresponding to the lisso-sphincter, and the other distal to the end of the prostate corresponding to the rhabdo-sphincter, surrounding a central urethral muscle fiber bundle, were clearly identified. FA was higher and λ3 lower in the proximal sphincter muscle compared to the central urethral muscle and the distal sphincter (P < 0.05). The average coefficient of variation ranged from 5-12% for the DTI indices. Since DTI values are known to reflect underlying tissue microarchitecture, significant differences in DTI indices identified here between the muscles of the urethral complex may potentially arise from differences in tissue microarchitecture that may in turn be related to the specific function of the sphincter and other muscles. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1002-1011.

Association between Magnetic Resonance Imaging Findings of the Pelvic Floor and de novo Stress Urinary Incontinence after Vaginal Delivery.

ObjectiveThe study aimed to evaluate the contributions of levator ani muscle (LAM) injury, vesical neck movement, urethral length and mobility, and urethral sphincter dysfunction observed on magnetic resonance imaging (MRI) towards stress urinary incontinence (SUI) after vaginal delivery.Materials and MethodsFifty primiparous women after 6 months of delivery (15 with SUI and 35 without) and 35 nulliparous as continent controls underwent MRI at rest and Valsalva maneuver. A published levator ani scoring system was used to characterize morphological changes of LAM. The severity of the injury was divided into three categories as none, minor, and major. A series of common parameters including levator plate angle, iliococcygeal angle, and levator hiatus were used to describe the functional conditions of LAM. Urethral mobility was defined based on the rotation of the urethra between Valsalva and rest status. Vesical neck movement was evaluated by its distance to the pubococcygeal line. Urethral sphincter dysfunction was defined as the widening of the proximal urethra and/or funneling at the urethrovesical junction during Valsalva.ResultsPrimiparous incontinent (PI) women had additional major levator ani defects (33.3% vs. 17.1%) while less minor defects (0.7% vs. 31.4%) than primiparous continent (PC) women. Vesical neck downward movement in PI women was more obvious than PC women (28.5 mm vs. 24.2 mm, p = 0.006). Urethral mobility was more active in primiparous women than in nulliparous continent controls (57.4 vs. 52.4), whereas no difference was observed on urethral mobility in the primiparous group (p = 0.25). Urethral sphincter dysfunction and funneling were present in 80% of PI women versus 22.9% in PC women (p < 0.001).ConclusionThe MRI findings revealed that de novo SUI was associated with major LAM injury, vesical neck downward movement as well as urethral sphincter dysfunction. Vesical neck funneling on sagittal images can be treated as a valuable predictor for SUI. The intervention for the PI should focus on the elevation of vesical neck, rehabilitation of LAM as well as recovery of the urethral sphincter muscle.

Microfluidic production of bioactive fibrin micro-beads embedded in crosslinked collagen used as an injectable bulking agent for urinary incontinence treatment.

Urinary incontinence is involuntary urine leakage, resulting from a deficient function of the sphincter muscle complex. Yet there is no functional cure for this devastating condition using current treatment options. Applied physical and surgical therapies have limited success. In this study, a novel bioactive injectable bulking agent, triggering new muscle regeneration at the injection site, has been evaluated. This injectable consists of cross-linked collagen and fibrin micro-beads, functionalized with bound insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1). These bioactive fibrin micro-beads induced human smooth muscle cell migration in vitro. Thus, this injectable bulking agent is apt to be a good candidate for regeneration of urethral sphincter muscle, ensuring a long-lasting treatment for urinary incontinence.

Pengaruh Pemberian Kompres Hangat Suprapubik Terhadap Pemulihan Reflek Vesica Urinaria Pada Pasien Post Spinal Anestesi Di RSU PKU Muhammadiyah Bantul

Spinal anesthesia causes urinary retention because the urethral sphincter muscle doesn't respond to urination desire. Whencircumstances continue the pressure inhibits the flow of urine occurs hydroureter, hydronephrosis and gradually kidneyfailure. Suprapubic warm compresses activated dopaminergic transmission in the mesolimbic central nervous system thateffectively improve circulation speeds recovery of vesica urinary reflex. This research is aimed to know the effect of warmcompress on the vesica urinaria recovery reflex in post spinal anesthesia patient at RS PKU Muhammadiyah Bantul. Thisstudy was an experimental study with quasy experiment type with Non Equivalent Control Group After Only Design. Thetreatment provided was suprapubic warm compress. Consecutive sampling with 40 respondents divided into control andintervention group that undergo spinal anesthesia at RSU PKU Muhammadiyah Bantul. Data analysis was done by Chisquare. In control group, 9 respondents (45%) had vesica urinary reflex recovery ≤ 8 hours, while in intervention group, 16respondents (20%) had vesica urinary reflex ≤ 8 hours. Chi Square test resulted on p value 0.022 (≤0,05). There is an effect ofsuprapubic warm compress toward vesica urinary reflex recovery in post spinal anesthesia patients at RSU PKUMuhammadiyah Bantul.

Uzing of endourethral and intravaginal electrostimulation of urethral sphincter and pelvic floor muscles іn complex treatment of women with stress urinary incontinence without prolapse of pelvic organs

Uzing of endourethral and intravaginal electrostimulation of urethral sphincter and pelvic floor muscles іn complex treatment of women with stress urinary incontinence without prolapse of pelvic organs

MP42-09 ATROGIN IS A NOVEL MARKER OF AGE-RELATED URETHRAL SPHINCTER MUSCLE ATROPHY

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2017MP42-09 ATROGIN IS A NOVEL MARKER OF AGE-RELATED URETHRAL SPHINCTER MUSCLE ATROPHY M. Raj Rajasekaran, Johnny Fu, My-Uyen (Lilly) Nguyen, and Valmik Bhargava M. Raj RajasekaranM. Raj Rajasekaran More articles by this author , Johnny FuJohnny Fu More articles by this author , My-Uyen (Lilly) NguyenMy-Uyen (Lilly) Nguyen More articles by this author , and Valmik BhargavaValmik Bhargava More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1298AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies show an age-related increase in the prevalence of urinary incontinence (UI) (10-15% in adults and ~30% % in older population >70 years). Age-related atrophic changes in urethral sphincter muscles are recognized as the most common cause for UI in the geriatric population. Recently, atrogin (a muscle-specific E3 ubiquitin ligase) is recognized as an important molecular pathway involved in age-related muscle atrophy. We tested the hypothesis that increased urethral sphincter atrophy during advanced aging is mediated by this novel atrogin pathway. METHODS We used a rabbit model to establish time course of age-related urethral sphincter muscle complex dysfunction and for further evaluation of molecular mechanisms of muscle dysfunction /atrophy in rabbits. We employed young (6-9 months), middle age (>12 months) and old rabbits (>30 months) and measured urethral muscle thickness (using transurethral ultrasound (US) technique (Fig A-inset) as well as urethral closure pressure (Fig A) in response to pelvic floor muscle electrical stimulation. We harvested bladder neck (for lissosphincter) and mid-urethra (for rhabdosphincter) samples to evaluate protein and mRNA levels of atrogin (marker of atrophy) using Western blot (protein) /qPCR studies respectively. RESULTS Our rabbit studies confirmed age-related changes in the urethral sphincter muscle thickness (Fig A) and alterations in closure pressure (Fig A) as well as in protein/mRNA levels of marker of atrophy (atrogin; Fig B-D) in both bladder neck and mid-urethra . These observations confirm our hypothesis that age-related increase in atrophy mediated via atrogin pathway may contribute to sphincter muscle dysfunction. CONCLUSIONS Our physiological, imaging and molecular studies are consistent with our hypothesis that age-related increase in atrogin protein contribute to sphincter muscle dysfunction. Targeting atrogin may be a novel approach to prevent age-related urethral sphincter muscle atrophy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e547 Advertisement Copyright & Permissions© 2017MetricsAuthor Information M. Raj Rajasekaran More articles by this author Johnny Fu More articles by this author My-Uyen (Lilly) Nguyen More articles by this author Valmik Bhargava More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP82-09 ENHANCEMENT OF SNEEZE-INDUCED URETHRAL CONTINENCE REFLEX VIA SEROTONIN TYPE 7 RECEPTORS IN RATS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II1 Apr 2017MP82-09 ENHANCEMENT OF SNEEZE-INDUCED URETHRAL CONTINENCE REFLEX VIA SEROTONIN TYPE 7 RECEPTORS IN RATS Takahisa Suzuki, Takahiro Shimizu, Joombeom Kwon, Eiichiro Takaoka, Shun Takai, Nobutaka Shimizu, Naoki Wada, Seiichiro Ozono, and Naoki Yoshimura Takahisa SuzukiTakahisa Suzuki More articles by this author , Takahiro ShimizuTakahiro Shimizu More articles by this author , Joombeom KwonJoombeom Kwon More articles by this author , Eiichiro TakaokaEiichiro Takaoka More articles by this author , Shun TakaiShun Takai More articles by this author , Nobutaka ShimizuNobutaka Shimizu More articles by this author , Naoki WadaNaoki Wada More articles by this author , Seiichiro OzonoSeiichiro Ozono More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2556AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The spinal serotonin (5HT) system is well known to be involved in the control of lower urinary tract function, and we previously reported that 5HT receptors such as 5HT1A or 5HT2C, have respectively inhibit or enhance the urethral continence reflex during sneezing in rats. However, because there are multiple 5HT receptor subtypes, it is often difficult to determine the subtype-specific mechanism. Thus, we examined the role of 5HT7 receptors in the urethral continence mechanism using a rat model of stress urinary incontinence (SUI), in which endogenous 5HT was depleted by p-chlorophenylalanine (PCPA). METHODS Female Sprague-Dawley rats were used. PCPA (200 mg/kg/day) was administered intraperitoneally for two days. Thereafter, using a microtransducer-tipped catheter inserted to the mid-urethra, we assessed urethral baseline pressure (UBP), amplitudes of urethral responses during sneezing (AURS) and abdominal pressure during sneezing (Pabd) under urethane anesthesia before and after administration of following drugs. First, we investigated the effects of a 5HT7 and partial 5HT1A agonist (LP 44 = LP, 0.3mg/kg, iv) in PCPA-administered rats. To suppress the partial 5HT1A effect of LP, a 5HT1A antagonist (WAY 100635 = WAY, 0.1 mg/kg, iv) was administered before LP treatment. Secondly, we investigated whether the effects of LP in the presence of WAY were inhibited by a 5HT7 antagonist (SB 269970 = SB, 0.1 mg/kg, iv), which was administered with WAY prior to LP administration. All data are shown in cmH2O. RESULTS After LP administration (n = 6), UBP and AURS were significantly increased compared to the PCPA + WAY (n = 4) or PCPA only group (n = 7) (UBP: 15.2 vs 16.8 vs 26.6, AURS: 30.0 vs 32.2 vs 50.5 [PCPA only vs PCPA + WAY vs PCPA + WAY + LP], respectively) (Figure). However, in the presence of the SB, UBP and AURS were not significantly increased after LP administration (n = 6) compared to the PCPA + WAY (n = 6) or PCPA only group (n = 6). Pabd had no statistical difference among groups. CONCLUSIONS The 5HT7 receptor exerts the facilitatory effects on the urethral baseline activity and the urethral continence reflex during stress conditions such as sneezing, which are reportedly attributable to contractions of smooth and striated urethral sphincter muscles, respectively. Thus, 5HT7 agonists could be effective for the treatment of SUI. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1100 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Takahisa Suzuki More articles by this author Takahiro Shimizu More articles by this author Joombeom Kwon More articles by this author Eiichiro Takaoka More articles by this author Shun Takai More articles by this author Nobutaka Shimizu More articles by this author Naoki Wada More articles by this author Seiichiro Ozono More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP42-08 MALE URETHRAL SPHINCTER COMPLEX REVISITED USING NOVEL MR IMAGING TECHNIQUES

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2017MP42-08 MALE URETHRAL SPHINCTER COMPLEX REVISITED USING NOVEL MR IMAGING TECHNIQUES Kyoko Sakamoto, Valmik Bhargava, Vadim Malis, M. Raj Rajasekaran, and Shantanu Sinha Kyoko SakamotoKyoko Sakamoto More articles by this author , Valmik BhargavaValmik Bhargava More articles by this author , Vadim MalisVadim Malis More articles by this author , M. Raj RajasekaranM. Raj Rajasekaran More articles by this author , and Shantanu SinhaShantanu Sinha More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1297AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Anatomical description of the male urethral sphincter complex (internal lissospincter and external rhabdosphincter) has undergone several revisions as previous conclusions were mostly derived from gross cadaveric dissection of adult male pelvis. These findings have been plagued by distortions of the anatomical structures in cadavers. Our objective was to elucidate the anatomy of the urethral sphincter muscles by resorting to in vivo, non-invasive imaging, using proton-density (PD), diffusion tensor imaging (DTI) and fiber tracking and thereby improve our understanding by avoiding the errors in cadaveric studies. METHODS Normal healthy five male young subjects, (mean age ~25 yrs) were scanned on a 3T GE MR scanner, using a multi-channel cardiac coil, lying supine, feet-first. After acquisition of a high resolution sagittal scout scan (Fig. A), axial morphological proton-density scans were prescribed and acquired extending from a few slices below the base of the bladder to beyond the entry of the urethra into the penis (~18-22 slices depending on the height of the subject). Three mm thick DTI scans were acquired and analyzed to obtain first the tensor axial images (Fig. B-C) to construct fibers within this urethral complex. RESULTS A consistent finding was that of possibly two sphincter like muscles (Fig. D-E), with one proximal near the bladder neck (yellow arrow in Fig. A, B) and the other more distal (Fig. C). In the tensor images, blue color indicates fibers oriented superior- inferior, red left-right while green anterior-posterior directions. Fiber tracking of these tensor images yields fiber structures within the urethral sphincter complex. The proximal sphincter is shown in Fig. D, the distal sphincter in Fig. E. The connecting superior-inferior longitudinal fibers are shown in blue in Fig. F. A consistent finding was the distance between the two sphincters is between 21 and 24 mm (i.e., 7 to 8 slices). CONCLUSIONS This is perhaps the first DTI and fiber tracking of the male urethral sphincter complex. Our findings support the two sphincter concept to constrict/close the urethral opening. These observations will form the basis of normal urethral morphology that can be monitored in post-surgery patients and correlated with age /urinary incontinence symptoms. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e546-e547 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kyoko Sakamoto More articles by this author Valmik Bhargava More articles by this author Vadim Malis More articles by this author M. Raj Rajasekaran More articles by this author Shantanu Sinha More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Sulforaphane Treatment of Stress Urinary Incontinence Via the Nrf2-ARE Pathway in a Rat Model

Background/Aims: To explore the effect of sulforaphane (SFN) treatment in rats through the induction of Stress Urinary Incontinence (SUI) via the Nrf2-ARE pathway. Methods: A total of 18 female rats (Sprague-Dawley) were assigned to three groups: a control group, an SUI group, and an SUI+SFN group (six rats per group). Rats in the treatment groups were induced via postpartum vaginal balloon dilation and bilateral ovariectomy. Rats in the SUI+SFN group were treated via intraperitoneal injection once per day for a total of one month. Urethral sphincter muscle histological was observed by HE and Masson staining. Peak voiding pressure and interval of micturition were measured by cystometry. Oxidative stress markers and protein expression in the Nrf2-ARE pathway were examined by immunohistochemical staining and western blotting. Results: Prolonged micturition interval and higher peak voiding pressure were observed in the SUI+SFN group. Disturbance of muscle morphology was ameliorated, muscle content was elevated, and collagen content was restrained in response to SFN treatment. The SOD, GSH-Px, and CAT activities were elevated in the SUI+SFN group compared to those in the control group. The level of cell apoptosis was decreased in SUI rats after SFN treatment; however, apoptosis was mainly located in the urethral mucosa instead of the muscle layer. SFN reduced the Bax/Bcl-2 expression ratio. Nrf2 and Nrf2 target antioxidant proteins were elevated in the SFN group. Conclusions: SFN was effective for SUI treatment via decreasing oxidative stress and activating the Nrf2-ARE pathway.

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

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.

Reconstruction of the Urethral Sphincter with Dynamic Graciloplasty in a Male Rabbit Model

Introduction: The use of artificial urinary sphincters can improve urinary incontinence after radical prostatectomies; however, complications can arise. We hypothesized that dynamic graciloplasty improves urethral sphincter reconstruction. Materials and Methods: Models of urethral sphincter muscle reconstruction were developed in 5 adult rabbits by wrapping the gracilis muscle flap around the urethra. Intra-urethral pressure was measured in each of the models before reconstruction (control), after reconstruction, and after electrical stimulation of the flap in reconstructed models (stimulated models). Results: The mean maximum urethral closure pressure was significantly greater in the reconstruction model (69.7 (66.5-115.8) mm Hg) than in the control model (39.2 (33.7-49.6) mm Hg). The mean integral of the urethral pressure and urethral length was also significantly greater in the reconstruction model than in the control model. Furthermore, sphincter tightening was enhanced by the electrical stimulation of the flap. Conclusions: Our results support our hypothesis that the functional reconstruction of urethral sphincters using muscle flaps is promising for the treatment of urinary incontinence.

Regeneration of degenerated urinary sphincter muscles: improved stem cell-based therapies and novel imaging technologies.

Stress urinary incontinence (SUI) is a largely ousted but significant medical, social, and economic problem. Surveys suggest that nowadays approximately 10% of the male and 15% of the female population suffer from urinary incontinence at some stage in their lifetime. In women, two major etiologies contribute to SUI: degeneration of the urethral sphincter muscle controlling the closing mechanism of the bladder outflow and changes in lower pelvic organ position associated with degeneration of connective tissue or with mechanical stress, including obesity and load and tissue injury during pregnancy and delivery. In males, the reduction of the sphincter muscle function is sometimes due to surgical interventions as a consequence of prostate cancer treatment, benign prostate hyperplasia, or of neuropathical origin. Accordingly, for women and men different therapies were developed. In some cases, SUI can be treated by physical exercise, electrophysiological stimulation, and pharmacological interventions. If this fails to improve the situation, surgical interventions are required. In standard procedures, endoprostheses for mechanical support of the weakened tissue or mechanical valves for a bladder outflow control are implanted. In 20% of cases treated, repeat procedures are required as implants yield all sorts of side effects in time. Based on preclinical studies, the application of an advanced therapy medicinal product (ATMP) such as implantation of autologous cells may be a curative and long-lasting therapy for SUI. Cellular therapy could also be an option for men suffering from incontinence caused by injury of the nerves controlling the muscular sphincter system. Here we briefly report on human progenitor cells, especially on mesenchymal stromal cells (MSCs), their expansion and differentiation to smooth muscle or striated muscle cells in vitro, labeling of cells for in vivo imaging, concepts of improved, precise, yet gentle application of cells in muscle tissue, and monitoring of injected cells in situ.