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Low urinary flow rates are frequently observed following tubularized incised plate urethroplasty. The underlying cause is not yet fully understood and may be associated with low urethral compliance. The purpose of this study is to non-invasively evaluate the urethral compliance in a rabbit model. Ten male New Zealand rabbits were randomly divided into a control group and a urethroplasty group for tubularized incised plate urethroplasty. Seven weeks post-operatively, ex vivo urethral compliance was evaluated using both the Jesus invasive measurement and the non-invasive method. The Jesus measurement involved measuring urethral volume and pressure by air insufflation, and the non-invasive method utilized ultrasound and uroflowmetry to assess the urethral anterior-posterior diameter and flow data, respectively. Curve regression analysis was applied to calculate urethral compliance. Curve regression analysis revealed that the median urethral compliance measured by non-invasive method in the control group was 0.247 (0.241, 0.257) mm•s/ml, and it was 0.269 (0.263, 0.270) mm•s/ml in the urethroplasty group, with no significant difference between the two groups. The Jesus method indicated median urethral compliance was 0.141 (0.137, 0.149) ml/cmH 2 O for the control group and 0.182 (0.173, 0.192) ml/cmH 2 O for the urethroplasty group, showing no significant statistical difference. In the rabbit model, urinary flow rate and anterior-posterior diameter serve as non-invasive indicators that can effectively reflect urethral compliance, and TIP surgery has no significant impact on urethral compliance.

The male urethra transports urine and semen. Any disease of the male urethra, hindering normal voiding or ejaculation, has a major impact on quality of life. Urethral stricture disease is common and molecular research into urethral strictures is hampered by the lack of reliable models of the human urethra. The aim of this project is to develop an in vitro model system of the human urethra. We hypothesized that by using the organ-on-a-chip technology we would be able to recapitulate physiology, functionality and the biomechanical cues of the native urethra and its surrounding vascular bed. Our approach consisted in using the F300R microfluidic device in combination with a rocking system to develop a potential urethra-on-a-chip. Urethral epithelial cells were used to mimic the native urethral epithelium. Gelatin-based hydrogels were tested for vasculogenic properties by placing the gel on the chick chorioallantoic membrane (CAM). Furthermore, the same gels were used for the formation of a micro vascular bed. Microvessel-like structures were formed in the gelatin-based hydrogels. Furthermore, these gels supported penetration, survival and proliferation of chicken endothelial cells when placed on the CAM. While we could only recapitulate a low fluidic shear stress (FSS) of 0.049 dyne/cm 2 , this was enough to form a confluent monolayer during dynamic conditions. This was not accomplished during static conditions. This project holds promise in mimicking the native layers of the urethra: epithelium and surrounding vascular tissue, under dynamic conditions. This new approach could provide a valuable platform to study the pathogenesis of urethral diseases and verify the effectiveness of drug treatment.

Background To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra‐sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa). Methods Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy × 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade ≥ 3 toxicity (including grade ≥ 2 for urinary obstruction/retention) during the first 3 months. Results Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ‐PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate. Conclusions At 18 months, urethra‐sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW). Dose per fraction and overall treatment time can impact tolerance of prostate SBRT. Urethra‐sparing SBRT showed a low toxicity profile and minimal impact on QoL. An EOD or QW SBRT schedule had a comparable tolerance and efficacy at 18 months.

Stress urinary incontinence (SUI) is a prominent incontinence caused by increased abdominal pressure. Sling treatments are surgical procedures used to treat SUI by inserting an artificial mesh into the urethra. However, after the sling treatments, patients can be at risk of chronic pain and infection in the urological system. The current research aims to develop new non-ablative transurethral laser treatment for SUI as a minimally invasive and non-implantable procedure. Six females porcine were randomly divided into three groups: Control, day 0 and day 28 after laser treatment. The urethra was dilated using a balloon-assisted diffusing applicator and irradiated with a 980-nm laser light at 20 W for 15 s. To compare the efficacy of the treatment, urethral tissues were harvested on days 0 and 28 for histological evaluation. 28 days after the laser treatment, the urethra thickness was 46% greater than the control group, indicating an increase in collagen deposition in the urethra. The transurethral laser treatment groups exhibited significantly higher levels of collagen reconstruction-related proteins (VEGF and collagen type 3), compared to the control group, without causing thermal damage to the urethral mucosa. The current findings demonstrated the feasibility of the non-ablative transurethral laser treatment for SUI without thermal damage to the urethral mucosa. Further investigations will be pursued to validate functional and molecular changes of the laser-treated urethra in a disease-induced animal model in order to warrant the efficacy and safety of the transurethral laser treatment for clinical translations.

In urethral damage/stricture prevention, open and harsh urethral microenvironments and isotropic compression and swelling properties of exogenous implants render urethral repair intractable. Here a dynamically urethra-adapted and obligations-oriented trilayer hydrogel was engineered to integrate scarless urethral repair. Therein, the diethylacrylamide-hydroxyethylacrylamide (HEAm) (D-H) hydrogel layer featuring high anti-fouling performance prevent adhesions of bacterial and blood cells, and its poor swelling avoids urethra occlusion. The upper swellable and verteporfin (VP)-loaded N,N’-methylenebisacrylamide-poly (N-isopropylacrylamide) (BP) layer encourages urethra regeneration through expediting cell migration and proliferation. The rigid and water-resistant Zein middle layer opposes urine voiding-arised BP shedding, urethral diastole/contraction, inward BP swelling-arised urethra occlusion and urine permeation. Importantly, systematic proteomic and genomic analysis reveals that such hydrogel scaffolds expedite epithelial & vascular regenerations, attenuate tight cell junction, oppose inflammation microenvironment and regulate extracellular matrix secretion and metabolism to realize integrated urethral repair. The microenvironment-adaptable design concepts provide reliable rationales to engineer urethral regeneration scaffolds. In urethral damage, exogenous implants designed for urethral repair are hindered by the open and harsh urethral microenvironments and the isotropic compression and swelling properties of the material. Here, Yang et al. develop a tri-layer hydrogel with anti-fouling and low-swelling properties for scarless urethral repair.

Chemosensory cells in the mucosal surface of the respiratory tract (“brush cells”) use the canonical taste transduction cascade to detect potentially hazardous content and trigger local protective and aversive respiratory reflexes on stimulation. So far, the urogenital tract has been considered to lack this cell type. Here we report the presence of a previously unidentified cholinergic, polymodal chemosensory cell in the mammalian urethra, the potential portal of entry for bacteria and harmful substances into the urogenital system, but not in further centrally located parts of the urinary tract, such as the bladder, ureter, and renal pelvis. Urethral brush cells express bitter and umami taste receptors and downstream components of the taste transduction cascade; respond to stimulation with bitter (denatonium), umami (monosodium glutamate), and uropathogenic Escherichia coli ; and release acetylcholine to communicate with other cells. They are approached by sensory nerve fibers expressing nicotinic acetylcholine receptors, and intraurethral application of denatonium reflexively increases activity of the bladder detrusor muscle in anesthetized rats. We propose a concept of urinary bladder control involving a previously unidentified cholinergic chemosensory cell monitoring the chemical composition of the urethral luminal microenvironment for potential hazardous content.

Urethral stricture is characterized by the chronic formation of fibrous tissue, leading to the narrowing of the urethral lumen. Despite the availability of various endoscopic treatments, the recurrence of urethral strictures remains a common challenge. Postsurgery pharmacotherapy targeting tissue fibrosis is a promising option for reducing recurrence rates. Although drugs cannot replace surgery, they can be used as adjuvant therapies to improve outcomes. In this regard, many drugs have been proposed based on the mechanisms underlying the pathophysiology of urethral stricture. Ongoing studies have obtained substantial progress in treating urethral strictures, highlighting the potential for improved drug effectiveness through appropriate clinical delivery methods. Therefore, this review summarizes the latest researches on the mechanisms related to the pathophysiology of urethral stricture and the drugs to provide a theoretical basis and new insights for the effective use and future advancements in drug therapy for urethral stricture.

Anoctamin-1 Ca 2+ -activated Cl − channels (ANO1) are proposed to modulate contractility of urethra smooth muscle cells (USMC), but their cellular expression and contribution to agonist/neural evoked activity is unclear. ANO1 is implicated as a potential target to treat incontinence, thus this is an important issue to resolve. We sought to clarify roles of ANO1 in contractility of mouse USMC. We found expression of Ano1 transcripts in murine urethra, with no difference between male and females. Immunolabelling revealed ANO1 was expressed in USMC and not in specialized populations of interstitial cells (c-kit + interstitial of Cajal-like cells (ICC-LC) and PDGFRα + cells). However, a specific ANO1 channel inhibitor, Ani9, failed to affect urethral contractions elicited by phenylephrine, arginine vasopressin or electrical field stimulation of intrinsic nerves. CaCC inh A01 also failed to affect urethral contractions. In addition, Ani9 had no effect on Ca 2+ signals generated by USMC in situ. In contrast, Ani9 effectively reduced spontaneous contractions and Ca 2+ signals of mouse proximal colon. In addition, Ani9 inhibited ANO1 currents recorded in HEK 293 cells, at concentrations 30 times less than those used in organ bath experiments. Our data suggest that despite expression of ANO1 in USMC, these channels do not contribute to basal Ca 2+ signalling, or agonist and neurally-evoked contractions in murine urethra.

Spinal Cord Injury (SCI) often leads to urinary incontinence. While alterations in the bladder have been considered the primary cause of post-SCI urinary dysfunction, evidence suggests that urethral afferents may influence post-SCI bladder activity. These afferents respond to locally produced serotonin (5-HT), and 5-HT signalling may likely be affected by SCI. Here, we investigated the role of urethral 5-HT on post-SCI bladder reflex activity using female C57BL/6 mice (wild-type -WT- and animals lacking urethral 5-HT (tryptophan hydroxylase 1 -tph1- null - tph1 −/− ). In WT animals, bladder overactivity and increased 5-HT + urethral cells were observed at one and four weeks post-SCI (1w and 4w, respectively), while, in contrast, tph1 −/− mice showed some preservation of bladder function. Both genotypes developed urethral smooth muscle atrophy 4w post-SCI, but fibrosis of striated muscle was detected only in tph1 −/− 4w SCI mice. Sensory and cholinergic fibres were upregulated only in WT SCI mice, suggesting 5-HT depletion may block their expansion. Pharmacological blockade of 5-HT receptors did not prevented urinary impairment but affected SCI-induced bladder dysfunction. These observations indicate that urethral 5-HT contributes to SCI-induced urinary impairment and urethral tissue reorganization, offering new insights into the urethrovesical reflex and potentially pinpointing new therapeutic targets.

Introduction and hypothesisThe objective was to determine whether standardized, intraoperative urethral measurement improves retropubic mid-urethral sling (RPMUS) positioning and if the intraoperative position remains stable at 2 weeks postoperatively.MethodsParticipants undergoing a RPMUS were randomized to mid-urethral placement as per usual surgical care (no Foley catheter measurement, no-FCM) vs urethral mid-point Foley catheter measurement (FCM). The primary outcomes were RPMUS location as determined by 2D and 3D ultrasound 2 weeks postoperatively (as percentage from urethral meatus − relative to the urethral length) and intraoperatively following the RPMUS placement.ResultsForty-four women enrolled, underwent RPMUS, and provided baseline data and intraoperative ultrasound measurements; of these, 36 (82%) had interpretable intraoperative and postoperative ultrasound measurements. Demographic data were similar in the two groups. The mean RPMUS mid-point was 57 % and 55 % in measured and controls (p = 0.685); this same measurement was relatively unchanged at 2 weeks postoperatively at 57% and 54% respectively (p = 0.538). Very much and much improvement was reported on the PGI-I by 84% and 85% of participants in the FCM and no-FCM groups respectively.ConclusionsIntraoperative RPMUS position at 2 weeks after surgery is similar to the intraoperative position. Compared with usual surgical care, intraoperative measurement of urethral mid-point with a Foley catheter did not affect RPMUS sling position.