This paper is concerned with the rate-dependent material properties of an aluminum thin foil. In the micro-scale tensile tests were conducted for Al1100 thin foils with thickness of 96 μm at various strain rates ranged from 1/s to 100/s using a High-Speed Micro Material Testing Machine (HSMMTM). The dimension of the test specimen was 1,500 μm in the gauge length and 300 μm in the gauge width. Test equipments designed and constructed for micro-tensile tests as well as a new jig system for easy installation and accurate alignment of a specimen between a specimen and the jig system. The jig mechanism developed enhances the reproducibility of experiments. Experimental results show that the flow stress of an aluminum thin foil increases more remarkable as the strain rate increases than the flow stress of an aluminum sheet with moderate thickness.

Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.

AIMS:Micromotion is an autonomous intramural movement of the bladder, and is believed to be an initial step in the generation of urinary urgency. Therefore, controlling micromotion may be a novel target in overactive bladder (OAB) treatment. However, developing micromotion treatment has been limited by the absence of a standardized animal model. We attempted to create a micromotion animal model and investigated the effectiveness of a β3 -adrenoceptor agonist (CL316,243) on micromotion.METHODS:Bilateral major pelvic ganglia (MPGs) were excised in 18 male Sprague-Dawley rats, resulting in an almost completely denervated bladder. On postoperative Day 7, cystometry was performed. Rats were divided into three treatment groups: CL316,243; β3- adrenoceptor antagonist (SR59230A) pretreated CL316,243; and a nonselective antimuscarinic agent (oxybutynin). Changes in micromotion were evaluated after the intra-arterial administration of each agent.RESULTS:Low-amplitude oscillations in intravesical pressure (micromotion) were observed 1 week after MPGs excision. Micromotion frequency significantly (p = 0.003) decreased (2.17 ± 3.54 times/5 min) with CL316,243 compared with vehicle (6.33 ± 1.97 times/5 min). Micromotion amplitude also decreased with CL316,243 (1.15 ± 1.93 cmH2 O) compared with vehicle (5.96 ± 5.12 cmH2 O), approaching conventional significance (p = 0.090). No significant decreases in frequency or amplitude were observed with oxybutynin treatment.CONCLUSIONS:Systemic administration of the β3 -adrenoceptor agonist CL316,243 effectively controlled micromotion in bilateral MPGs-excised, almost completely denervated rat bladders. This result indicates that β3 -adrenoceptor agonist may affect the bladder directly, suggesting that it might be effective for overall OAB, regardless of the presence or level of neurological deficits. Bilateral MPGs-excised rats are considered a plausible micromotion animal model suitable for future research.

The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the urinary bladder, urethra, and external urethral sphincter. This activity is in turn controlled by neural circuits in the brain, spinal cord, and peripheral ganglia. Various neurotransmitters, including acetylcholine, norepinephrine, dopamine, serotonin, excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide, and neuropeptides, both in the periphery and the central nervous system have been implicated in the neural regulation of the lower urinary tract. Injuries or diseases of the nervous system, as well as drugs and disorders of the peripheral organs, can produce voiding dysfunctions such as urinary frequency, urgency, pain and incontinence, or inefficient voiding and urinary retention. This chapter reviews recent advances in our understanding of the pharmacology in the control of lower urinary tract function and the targets for drug therapy.

Due to the short storage period, large quantities of platelet concentrate (PC) are expiring. The expired PC cannot be injected into a blood vessel, but the activity of bioactive molecules, especially growth factors, is still preserved. In this paper, we organized a process to obtain a growth factor-rich bioproduct for use as a supplement in human cell culture by optimizing freezing, thawing, and sterilization conditions. Each unit of PC displayed visual differences, diverse biochemical values, and growth factor concentrations. To minimize lot-to-lot variation, we pooled a minimum of 10 PC units. The concentrations of growth factors were maximized through five freeze–thaw cycles for 12 h at −80 °C for freezing and for 5 min at 36 °C for thawing. We used a cell strainer with 40 µm pores, followed by a 0.45 μm filter and a 0.22 μm filter sequentially to sterilize the bioproduct with minimizing loss. The obtained growth factors remained stable for 4–6 h at room temperature (23 °C), 24 h at 4 °C, and 12 months at −80 °C. Cellular responses to the growth factor-rich bioproduct were tested with primary human renal proximal tubule epithelial cells. The cells exhibited a significantly increased growth rate, compared to the fetal bovine serum (FBS)-treated control group. The cells maintained their characteristic cuboidal shape, and stem cells and renal progenitor cells also preserved their genetic characteristics during culture. Therefore, the growth factor-rich bioproduct isolated from expired PC through our process can be used as a medium supplement to replace FBS in human cell culture for clinical application.

This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder–urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.

Purpose: Vibegron, a novel, potent β3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB.Methods: A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis.Results: Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients’ quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume.Conclusions: Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB.

This review article aims to summarize the recent advancement in basic research on lower urinary tract dysfunction (LUTD) following spinal cord injury (SCI) above the sacral level. We particularly focused on the neurophysiologic mechanisms controlling the lower urinary tract (LUT) function and the SCI-induced changes in micturition control in animal models of SCI. The LUT has two main functions, the storage and voiding of urine, that are regulated by a complex neural control system. This neural system coordinates the activity of two functional units in the LUT: the urinary bladder and an outlet including bladder neck, urethra, and striated muscles of the pelvic floor. During the storage phase, the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure and continence, and during the voiding phase, the outlet relaxes and the bladder contracts to promote efficient release of urine. SCI impairs voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following SCI, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However, the bladder does not empty efficiently because coordination between the bladder and urethral sphincter is lost. In animal models of SCI, hyperexcitability of silent C-fiber bladder afferents is a major pathophysiological basis of neurogenic LUTD, especially detrusor overactivity. Reflex plasticity is associated with changes in the properties of neuropeptides, neurotrophic factors, or chemical receptors of afferent neurons. Not only C-fiber but also Aδ-fiber could be involved in the emergence of neurogenic LUTD such as detrusor sphincter dyssynergia following SCI. Animal research using disease models helps us to detect the different contributing factors for LUTD due to SCI and to find potential targets for new treatments.

There is no clear pathophysiologic evidence determining how long overactive bladder (OAB) medication should be continued. We, therefore, investigated the effect of mirabegron using cessation (CES) or continuation (CON) treatment in an OAB animal model.

You have accessJournal of UrologyCME1 May 2022PD08-07 ANTIFIBROSIS TREATMENT IMPROVES BLADDER DYSFUNCTION AND PAIN PERCEPTION IN A MOUSE MODEL OF BLADDER PAIN WITH CENTRAL SENSITIZATION MIMICKING INTERSTITIAL CYSTITIS Joonbeom Kwon, Hye-Ri Park, Eun-Ju Lee, Ji-Ae Jang, Hyun-Jung Cho, and Naoki Yoshimura Joonbeom KwonJoonbeom Kwon More articles by this author , Hye-Ri ParkHye-Ri Park More articles by this author , Eun-Ju LeeEun-Ju Lee More articles by this author , Ji-Ae JangJi-Ae Jang More articles by this author , Hyun-Jung ChoHyun-Jung Cho More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002527.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies reported the possibility that the interruption of fibrosis may improve interstitial cystitis (IC). In addition, our previous study with nintedanib, which has an antifibrotic effect and inhibits the receptors of VEGF, FGF, and PDGF, demonstrated the improvement of bladder overactivity and C-fiber hyperexcitability in spinal cord injured mice. Therefore, we investigated whether antifibrotic therapy using nintedanib can improve the IC-like pathologic conditions. METHODS: Female C57BL/6 mice were divided into 3 groups (each N=8): (A) Sham, (B) IC mice treated with vehicle, and (C) IC mice treated with nintedanib. For inducing an IC-like model, intravesical instillation of hyaluronidase mixed with lipopolysaccharide was conducted 3 times once a week. At the last instillation, vehicle or nintedanib (50mg/kg) was administered daily for 3 weeks. Then, pain assessment using Von-Frey filaments and cystometry was conducted. Trichrome staining, RT-PCR in the bladder, and immunohistochemistry of L6-S1 dorsal root ganglia (DRG) and L6 spinal cord were performed to investigate the improvement of bladder fibrosis, inflammation, nociception, and central sensitization. RESULTS: In pain assessment, 50% thresholds of target force were significantly reduced in group B vs. A, but recovered in group C vs. B. In cystometry, non-voiding contractions and voiding efficiency were worsened in group B, but restored in group C (Fig 1-a). Bladder fibrosis increased in group B were improved in group C in trichrome staining (Fig.1-b). mRNA levels in the bladder related to inflammation (IFN-r, CCR2), nociception (TACR2), P2X purinergic (P2X3, P2X4, P2X7), muscarinic (M2), and β-adrenergic receptors (β2, β3) were increased in group B, but decreased in group C (Fig 1-c). In immunohistochemistry, TRPV1 in L6-S1 DRG and CX3CR1, GFAP, and CCR2 in L6 spinal cord were upregulated in group B, but reduced in group C (Fig 1-d). CONCLUSIONS: Antifibrosis treatment using nintedanib improved bladder pain and bladder overactivity in the IC model. Therapeutic effects seem to be mediated by inhibitions of bladder afferent hyperexcitability as well as central sensitization. Source of Funding: National Research Foundation of Korea (2020R1C1C1012208) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e107 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joonbeom Kwon More articles by this author Hye-Ri Park More articles by this author Eun-Ju Lee More articles by this author Ji-Ae Jang More articles by this author Hyun-Jung Cho More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 May 2022MP49-15 OVERACTIVE BLADDER MEDICATION; HOW LONG SHOULD IT BE CONTINUED? - MIRABEGRON INTERFERES WITH CENTRAL SENSITIZATION IN A MOUSE MODEL OF OVERACTIVE BLADDER Joonbeom Kwon, Eun-Ju Lee, Hye-Ri Park, Hyun-Jung Cho, Ji-Ae Jang, Donghwi Park, and Naoki Yoshimura Joonbeom KwonJoonbeom Kwon More articles by this author , Eun-Ju LeeEun-Ju Lee More articles by this author , Hye-Ri ParkHye-Ri Park More articles by this author , Hyun-Jung ChoHyun-Jung Cho More articles by this author , Ji-Ae JangJi-Ae Jang More articles by this author , Donghwi ParkDonghwi Park More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002624.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The etiology of overactive bladder (OAB) is multifactorial, and bladder afferent hyperexcitability has been proposed to be one of the contributing factors. In addition, chronic afferent hyperexcitability may induce neural remodeling in the central nervous system (CNS). However, there has been no clear pathophysiologic evidence determining how long OAB treatments should be continued. We, therefore, investigated the CNS effect of mirabegron using an OAB animal model and compared the therapeutic effect between treatment cessation (CES) and continuation (CON) groups. METHODS: Female C57BL/6 mice were divided into 4 groups (N=8 in each): Sham, OAB, CES, and CON groups. OAB was induced by 3-times weekly intravesical instillations of KCl and hyaluronidase. Mirabegron (2mg/kg) was administered for 10 and 20 days in CES and CON groups, respectively. Cystometry was performed, and mRNA levels of bladder muscarinic, β-adrenergic, and P2X purinergic receptors were measured. CCL2 and CCR2 in L6-S1 dorsal root ganglia (DRG), as afferent markers, and CX3CR1, GFAP, and CCR2 in the L6 spinal cord, as markers of glial activation and central sensitization, were also evaluated by RT-PCR and immunohistology. RESULTS: OAB mice showed bladder overactivity and inefficient voiding (Fig 1-a) with increased M2, M3, P2X2, P2X3, P2X4, and P2X7 levels in the bladder and increased CCL2 and CCR2 in DRG, indicating afferent hyperexcitability (Fig 1-b). CX3CR1, GFAP, and CCR2 in the L6 spinal cord were upregulated in the OAB group (Fig 1-c). However, CON mice exhibited improvements of all these parameters of afferent hyperexcitability and central sensitization. Also, CON mice showed better voiding efficiency and reduced CNS changes compared with CES mice. CONCLUSIONS: Central sensitization may be an important pathophysiological mechanism of OAB. Continuous treatment of OAB with mirabegron seems to prevent the process of central sensitization via improvement of CNS neural remodeling. Therefore, continuous OAB medication may be desirable for long-term disease control. Source of Funding: Astellas Pharma. Co.Ltd. (ISR005728) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e859 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joonbeom Kwon More articles by this author Eun-Ju Lee More articles by this author Hye-Ri Park More articles by this author Hyun-Jung Cho More articles by this author Ji-Ae Jang More articles by this author Donghwi Park More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF downloadLoading ...

Aims Spinal cord injury (SCI) above the sacral level causes bladder dysfunction and remodeling with fibrosis. This study examined the antifibrotic effects using nintedanib, an inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors, on detrusor overactivity (DO) and bladder fibrosis, as well as the modulation mechanisms of C-fiber afferent pathways. Methods Thirty female C57BL/6 mice were divided into group A (spinal intact), group B (SCI with vehicle), and group C (SCI with nintedanib). At 2 weeks after SCI, vehicle or 50 mg/kg nintedanib was administered subcutaneously for 2 weeks. Then, cystometry was conducted, followed by RT-PCR measurements of fibrosis-related molecules, muscarinic, beta-adrenergic, TRP and purinergic receptors in the bladder or L6-S1 dorsal root ganglia (DRG). Trichrome stain and Western blot analysis of transforming growth factor-beta and fibronectin were performed in the bladder. TRPV1 expression in L6 DRG was measured by immunohistochemistry. Results In cystometry, intercontraction intervals, nonvoiding contractions, voided volume, and voiding efficiency were significantly improved in group C versus group B. RT-PCR, Western blotting, and trichrome staining revealed the fibrotic changes in the bladder of group B, which was improved in group C. Increased messenger RNA levels of TRPV1, TRPA1, P2X(2), and P2X(3) in DRG of group B were significantly decreased in group C. TRPV1 immunoreactivity in DRG was increased in group B, but decreased in group C. Conclusions Nintedanib improves storage and voiding dysfunctions and bladder fibrosis in SCI mice. Also, nintedanib-induced improvement of DO is associated with reduced expression of C-fiber afferent markers, suggesting the modulation of bladder C-fiber afferent activity.

Currently, the midurethral sling (MUS) is widely used as a standard treatment in patients with stress urinary incontinence (SUI). Several studies have reported the failure rate of MUS to be approximately 5%–20%. In general, sling failure can be defined as persistent SUI after surgery or a temporary improvement in incontinence followed by recurrence. Failure is also often considered to include cases requiring secondary surgery due to mesh exposure, postoperative voiding difficulty, de novo urgency/urge incontinence, and severe postoperative pain. Because of the lack of large-scale, high-quality research on this topic, no clear guidelines exist for second-line management. To date, transurethral bulking agent injections, tape shortening, repeat MUS, pubovaginal sling (PVS) using autologous fascia, and Burch colposuspension are available options for second-line surgery. Repeat MUS is the most widely used second-line surgical method at present. Bulking agent injections have lower durability and efficacy than other treatments. Tape shortening demonstrates a relatively low success rate, but comparable outcomes if the period from first treatment to relapse is short. In patients with intrinsic sphincter deficiency, PVS and retropubic (RP) MUS can be considered first as second-line management because of their higher success rate than other treatments. When revision or reoperation is required due to prior mesh-related complications, PVS or colposuspension, which is performed without a synthetic mesh, is appropriate for second-line surgery. For patients with detrusor underactivity, a readjustable sling can be a better option because of the high risk of postoperative voiding dysfunction in PVS or RP slings.

Aims The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. Methods Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. Results PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. Conclusions PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU.

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

Background and Objectives: The purpose of this study was to compare two methods (transperitoneal laparoscopic ureterolithotomy [TLU] and a combination of ureteroscopic lithotripsy [UL] with retrograde intrarenal surgery [RIRS]) designed for the treatment of large proximal ureteral calculi so that their associated complications and stone-free rates could be assessed. Methods: A total of 100 patients from three different hospitals who were diagnosed with large upper ureteral stones (≥15 mm) were treated via TLU (n = 48) or UL-RIRS (n = 52). They were treated between March 2012 and May 2014. The study compared the complications, success rate, patient characteristics, and the operation time between the two groups. Results: The immediate stone clearance rate after a single session was higher in the TLU group than in the UL-RIRS group (100% vs 73.1%, P = .005). However, there was no significant difference in the stone-free rates between the two groups three months after the last procedure was performed (100% vs 96.1%, P = .655). Regarding patients with a history of early-failure extracorporeal shock-wave lithotripsy, there was no significant difference in the stone-free rate between the two groups three months after the last procedure (100% vs 94.4%, P > .05). Further, overall complication rates between the groups were not statistically different (P = .261). Conclusion: This study demonstrates that TLU is an effective and safe procedure to treat large impacted upper ureteral stones. When compared to UL-RIRS, TLU showed equivalent efficacy and safety, though there were failed first-line treatments.

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

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II1 Apr 2018MP38-12 URETHRAL DYSFUNCTION AND THERAPEUTIC EFFECTS OF A PDE 5 INHIBITOR (TADALAFIL) IN A RAT MODEL OF NEUROGENIC UNDERACTIVE BLADDER INDUCED BY PELVIC NERVE CRUSH Ei-ichiro Takaoka, Shun Takai, Takahisa Suzuki, Nobutaka Shimizu, Joonbeom Kwon, Hiroki Okada, Christopher J. Chermansky, Jun Miyazaki, and Naoki Yoshimura Ei-ichiro TakaokaEi-ichiro Takaoka More articles by this author , Shun TakaiShun Takai More articles by this author , Takahisa SuzukiTakahisa Suzuki More articles by this author , Nobutaka ShimizuNobutaka Shimizu More articles by this author , Joonbeom KwonJoonbeom Kwon More articles by this author , Hiroki OkadaHiroki Okada More articles by this author , Christopher J. ChermanskyChristopher J. Chermansky More articles by this author , Jun MiyazakiJun Miyazaki More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1239AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To characterize the urethral dysfunction and the effect of a phosphodiesterase 5 (PDE 5)inhibitor, Tadalafil, in a rat model of peripheral neurogenic detrusor underactivity (DU)/under active bladder (UAB) induced by pelvic nerve crush (PNC) injury. METHODS PNC rats were made by partial compression of visceral branches of the bilateral pelvic nerves. After 10 days, awake cystometrograms (CMG) as well as simultaneous recordings of isovolumetric CMG and urethral perfusion pressure (IC-UPP) were performed. Also, in normal rats, IC-UPP was recorded with atropine to examine if the attenuated isovolumetric bladder contraction affects urethral relaxation. Moreover, in PNC rats, the effects Tadalafil on CMG and IC-UPP parameters. We also evaluated the transcription levels of nNOS, eNOS, and PDE 5 at urethral specimens of PNC and normal rats. RESULTS In CMG, PNC rats showed significant increases in bladder capacity, post-void residual urine volume, non-voiding contractions, and intercontraction intervals (ICI) while bladder contraction amplitude was significantly decreased compared to normal rats. In IC-UPP study, PNC rats revealed significantly decreases in amplitudes of isovolumetric bladder contraction and urethral relaxation during bladder contraction. Atropine (0.4mg/kg, i.v.) attenuated the amplitude of isovolumetric bladder contractions, but not that of urethral relaxation. In CMG, Tadalafil (1mg/kg, i.v.) decreased post-void residual urine volume and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Tadalafil also improved the amplitude of urethral relaxation during bladder contraction in PNC rats (figure). In urethral tissues, nNOS transcript levels were upregulated in PNC rats vs. normal rats. CONCLUSIONS PNC rats, which is a model of peripheral neurogenic DU/UAB, revealed not only DU, but also impaired urethral relaxation. PDE 5 inhibition enhanced urethral relaxation during voiding, resulting in improved voiding efficiency in this model. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU/UAB. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e505 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ei-ichiro Takaoka More articles by this author Shun Takai More articles by this author Takahisa Suzuki More articles by this author Nobutaka Shimizu More articles by this author Joonbeom Kwon More articles by this author Hiroki Okada More articles by this author Christopher J. Chermansky More articles by this author Jun Miyazaki More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...