Bladder Detrusor Muscle Research Articles

Urinary Incontinence Associated with Sertraline use in a Young SSRI-Naí¯ve Female Patient: a Case Report

Introductions: Urinary incontinence is a side effect of several antidepressants, especially those in the SSRI and SNRI groups. Sertraline, a popular SSRI effective against a wide range of mental disorders, is one such drug with a clear association with a new onset of UI. Case: A 20-year-old Indonesian Chinese woman, presenting with mixed anxiety and depressive symptoms, was initially treated with sertraline 50 mg. She experienced an acute onset of urinary urgency and a loss of bladder control. These symptoms resolved upon discontinuation of sertraline. She was then given 10 mg of fluoxetine, and she noted that the urinary problems did not return. The medication was gradually tapered up to 40 mg/day with no remarkable adverse events. Discussions: Sertraline tends to stimulate micturition through effects on M3 muscarinic receptors on the bladder's detrusor muscle and inhibition of the dopamine transporter in the central nervous system. On the other hand, fluoxetine acts antagonistically on 5-HT2C, inhibiting the voiding reflex and promoting urinary continence. Therefore, though both are SSRIs, sertraline and fluoxetine may exhibit different, clinically meaningful effects. Conclusions: Clinicians need to have a greater awareness of urinary incontinence as a side effect of sertraline, as it impacts patients' adherence and quality of life. When possible, switching to fluoxetine is recommended for patients with urinary problems in the event of sertraline use.

Nitrergic inhibition of sympathetic arteriolar constrictions in the female rodent urethra.

During the urine storage phase, tonically contracting urethral musculature would have a higher energy consumption than bladder muscle that develops phasic contractions. However, ischaemic dysfunction is less prevalent in the urethra than in the bladder, suggesting that urethral vasculature has intrinsic properties ensuring an adequate blood supply. Diameter changes in rat or mouse urethral arterioles were measured using a video-tracking system. Intercellular Ca2+ dynamics in arteriolar smooth muscle (SMCs) and endothelial cells were visualised using NG2- and parvalbumin-GCaMP6 mice, respectively. Fluorescence immunohistochemistry was used to visualise the perivascular innervation. In rat urethral arterioles, sympathetic vasoconstrictions were predominantly suppressed by α,β-methylene ATP (10μM) but not prazosin (1μM). Tadalafil (100nM), a PDE5 inhibitor, diminished the vasoconstrictions in a manner reversed by N-ω-propyl-l-arginine hydrochloride (l-NPA, 1μM), a neuronal NO synthesis (nNOS) inhibitor. Vesicular acetylcholine transporter immunoreactive perivascular nerve fibres co-expressing nNOS were intertwined with tyrosine hydroxylase immunoreactive sympathetic nerve fibres. In phenylephrine (1μM) pre-constricted rat or mouse urethral arterioles, nerve-evoked vasodilatations or transient SMC Ca2+ reductions were largely diminished by l-nitroarginine (l-NA, 10μM), a broad-spectrum NOS inhibitor, but not by l-NPA. The CGRP receptor antagonist BIBN-4096 (1μM) shortened the vasodilatory responses, while atropine (1μM) abolished the l-NA-resistant transient vasodilatory responses. Nerve-evoked endothelial Ca2+ transients were abolished by atropine plus guanethidine (10μM), indicating its neurotransmitter origin and absence of non-adrenergic non-cholinergic endothelial NO release. In urethral arterioles, NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions pre- and post-synaptically to restrict arteriolar contractility. KEY POINTS: Despite a higher energy consumption of the urethral musculature than the bladder detrusor muscle, ischaemic dysfunction of the urethra is less prevalent than that of the bladder. In the urethral arterioles, sympathetic vasoconstrictions are predominately mediated by ATP, not noradrenaline. NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions by its pre-synaptic inhibition of sympathetic transmission as well as post-synaptic arteriolar smooth muscle relaxation. Acetylcholine released from parasympathetic nerves contributes to endothelium-dependent, transient vasodilatations, while CGRP released from sensory nerves prolongs NO-mediated vasodilatations. PDE5 inhibitors could be beneficial to maintain and/or improve urethral blood supply and in turn the volume and contractility of urethral musculature.

Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome.

Overactive bladder (OAB) is an age-related disorder characterised by unstable bladder contractions resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual's quality of life. The development of LUTS may be linked to the overexpression of oxytocin receptors (OXTRs) within the bladder detrusor muscle, resulting in increased baseline myogenic tone. Thus, it is hypothesised that targeting OXTRs within the bladder using oxytocin antagonists may attenuate myogenic tone within the bladder, thereby providing a new therapeutic avenue for treating OAB. Organ bath contractility and immunohistochemistry techniques were conducted on bladder tissue sourced from young rats (7-8 weeks and 10-12 weeks) and older rats (4-5 months and 7-9 months). Organ bath studies revealed that oxytocin (OT) significantly increased bladder contractions, which were significantly attenuated by [β-Mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2, Orn8]-Oxytocin) (1 µM) (**** p < 0.0001) and atosiban (10 µM) in both young and older rats (** p < 0.01); in contrast, cligosiban (1 µM and 10 µM) did not inhibit OT-induced contractions in both young and older rats (p ≥ 0.05). Interestingly, cligosiban (1 µM and 10 µM) significantly reduced the frequency of spontaneous contractions within the bladder of both young (*** p < 0.001) and older rats (**** p < 0.0001), while atosiban (10 µM) only demonstrated this effect in older rats (** p < 0.01). Furthermore, immunohistochemistry (IHC) analysis revealed significant colocalization of nuclear-specific oxytocin receptors (OXTRs) in the contractile (smooth muscle) cells within young (** p < 0.01) and older rats (* p < 0.05), indicating OT may be a key modulator of bladder contractility.

The Surgical Treatment of Advanced Urinary Incontinence

Purpose: Current treatments of urgency urinary incontinence (UUI) are aimed to reduce the neurological influence on bladder detrusor muscle function. A previous observation after posterior exenteration led to the hypothesis that UUI is caused by a laxity of the uterosacral ligaments (USL). In a previous Clinical Phase I trial in patients with UUI continence was achieved in 40% of patients by replacement of the USL. The results supported the concept of a Clinical Phase II trial in which only patients who lost urine after urgency (advanced UI) were treated by replacement of the USL. The aim of the study was to evaluate the cause why some patients became continent while others remained incontinent after replacement of the USL. Methods: In this Clinical Phase II trial, patients with advanced UI were included. The USL was replaced by specially designed polyvinylidene fluoride (PVDF) structures. During laparoscopy these structures were fixed at the promontory and at the cervical stump after supracervical hysterectomy (cervicosacropexy, CESA) or at the vaginal stump (vaginosacropexy, VASA). The USL replacing parts of the structures had an identical length of 8.8 cm in CESA and 9.3 cm in VASA. Patients who remained incontinent after tensioning of the vagina were offered a suburethral trans-obturator tape (TOT). Results: 339 patients with advanced urinary incontinence (UI) were evaluable. Continence was re-established in 39% of patients after CESA and in 32.9% after VASA. The statistical analysis revealed that the Continence Rates (CR) after CESA or VASA were significantly (p&lt;0.001) dependent on patients age at surgery (&lt;60 years vs ≥60 years). The respective CR after CESA were 50% vs 26% and after VASA 41.5% vs 28.9%. After an additional transobturator tape (TOT) the overall CR was between 67.5% and 87.5%. Conclusion: The replacement of the USL by PVDF-tapes of defined length led to continence in between 32.9% and 39% of the patients. After the additional placement of a TOT 8/4 the percentage of continent patients increased by 30.5% to 37.3%. These findings support the hypothesis that continence is dependent on the physiological function of the USL and PUL. The observation that the CR after USL replacement decreased in patients ≥60 years indicates that ageing affected some additional other part in the area of the urethra-vesical junction (UVJ). The CR after CESA or VASA (and a TOT) in patients with advanced UI deserve further clinical evaluation.

A consensus statement on when to start clean intermittent self-catheterization: An untapped resource?

Clean intermittent self-catheterisation (CISC or ISC) is used by patients/carers to empty the bladder if needed. Sometimes the urethral lumen leading out of the bladder is blocked; sometimes, the bladder (detrusor) muscle itself or the autonomic motor nerves innervating the bladder are damaged, resulting in a failure of the detrusor muscle to work, leading to a failure of the bladder being able to empty adequately. Prior consensus as to the indications and timing of CISC has yet to be provided. This article aims to provide a multidisciplinary consensus view on this subject. It is evident that every patient needs to be considered individually, bearing in mind the symptoms and investigations to be considered. We emphasise the importance of considering the term Bladder Voiding Efficiency (BVE). One group of patients who might find CISC helpful are those with a neurological disorder; these include spinal injury patients, multiple sclerosis, Parkinson's, and a condition called cauda equina. Sometimes bladder problems are treated with anticholinergics, and others may be treated with Botox. These may cause the bladder not to empty at all, which is good for leaks but needs self-catheterisation to empty the bladder. In the past, hospitals used a permanent catheter called an 'indwelling' or a 'suprapubic' catheter. These can have side effects, including infections, stones, and pain. For CISC, disposable catheters are the best option for patients as they come in different sizes and styles to provide individualised care. In conclusion, we would like hospitals to consider each patient separately and not use a general 'one-size-fits-all' bladder function for these patients.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

The role of intracellular calcium and Rho kinase pathways in G protein-coupled receptor-mediated contractions of urinary bladder urothelium and lamina propria.

The influence of extracellular and intracellular calcium on smooth muscle contractile activity varies between organs. In response to G protein-coupled receptor (GPCR) stimulation, the urinary bladder detrusor muscle has shown a 70% dependence on extracellular calcium, whereas the urothelium and lamina propria (U&LP) has a 20%-50% dependence. However, as this only accounts for partial contractile activity, the contribution of intracellular calcium and calcium sensitization pathways remains unclear. This study assessed the role of intracellular signaling pathways on GPCR-mediated urinary bladder U&LP contraction. Porcine U&LP responses to activation of the Gq/11-coupled muscarinic, histamine, 5-hydroxytryptamine (serotonin), neurokinin, prostaglandin, and angiotensin II receptors were assessed with three selective inhibitors of store-released intracellular calcium, 2-aminoethyl diphenylborinate (2-APB), cyclopiazonic acid (CPA), and ruthenium red, and three Rho kinase inhibitors, fasudil, Y-27632, and GSK269962. There was no discernible impact on receptor agonist-induced contractions of the U&LP after blocking intracellular calcium pathways, suggesting that this tissue is more sensitive to alterations in the availability of extracellular calcium. However, an alternative mechanism of action for GPCR-mediated contraction was identified to be the activation of Rho kinase, such as when Y-27632 significantly reduced the GPCR-mediated contractile activity of the U&LP by approximately 50% (P < 0.05, n = 8). This suggests that contractile responses of the bladder U&LP do not involve a significant release of calcium from intracellular stores, but that Gq/11-coupled receptor activation causes calcium sensitization via Rho kinase. This study highlights a key role for Rho kinase in the urinary bladder, which may provide a novel target in the future pharmaceutical management of bladder contractile disorders.

İzole Sıçan Mesane Detrusor Kasında Omeprazolün Etkisi ve Bu Etkide Rac-1 Yolağının Rolü

Introduction: The urinary retention problem reported in some patients using omeprazole and other proton pump inhibitors suggests that this drug has this effect by relaxing the bladder smooth muscle. Studies with omeprazole and other proton pump inhibitors show that these drugs cause relaxation in various tissue and organ smooth muscles, which also supports our hypothesis. However, there is no study in the literature about the possible effect and mechanism of action of omeprazole on bladder smooth muscle. The aim of this study is to investigate the possible effect and mechanism of action of omeprazole in isolated rat bladder detrusor muscle. Materials and Methods: In the presence of omeprazole (10-4, 5x10-4, 10-3 M), contraction responses induced by acetylcholine (10-6-10-3 M) and electrical field stimulation (2-64 Hz) were measured. Rac-1 pathway inhibitor NSC23799 (10-4 M) was used to investigate the mechanism of action of omeprazole. One-way analysis of variance (ANOVA) and Tukey-Kramer post-hoc test were used for statistical analysis. Results: Omeprazole (10-4, 5x10-4, 10-3 M) dose-dependently inhibited maximal contraction responses induced by acetylcholine and electrical field stimulation. When omeprazole (5x10-4 M) was applied in combination with NSC23766, it caused a significant increase in ACh and EFS-induced responses compared to the NSC23766 alone group. Conclusion: These results show that omeoprazole inhibits contractions in isolated rat detrusor muscle through blockade of Rac-1 pathway. Keywords: Detrusor Muscle, Omeprazole, Rac-1 Pathway, Rat

İzole Sıçan Mesane Detrusor Kasında Omeprazolün Etkisi ve Bu Etkide Rac-1 Yolağının Rolü

ABSTRACT The Effect of Omeprazole on Isolated Rat Bladder Detrusor Muscle and the Role of the Rac-1 Pathway in This Effect Introduction: The urinary retention problem reported in some patients using omeprazole and other proton pump inhibitors suggests that this drug has this effect by relaxing the bladder smooth muscle. Studies with omeprazole and other proton pump inhibitors show that these drugs cause relaxation in various tissue and organ smooth muscles, which also supports our hypothesis. However, there is no study in the literature about the possible effect and mechanism of action of omeprazole on bladder smooth muscle. The aim of this study is to investigate the possible effect and mechanism of action of omeprazole in isolated rat bladder detrusor muscle. Materials and Methods: In the presence of omeprazole (10-4, 5x10-4, 10-3 M), contraction responses induced by acetylcholine (10-6-10-3 M) and electrical field stimulation (2-64 Hz) were measured. Rac-1 pathway inhibitor NSC23799 (10-4 M) was used to investigate the mechanism of action of omeprazole. One-way analysis of variance (ANOVA) and Tukey-Kramer post-hoc test were used for statistical analysis. Results: Omeprazole (10-4, 5x10-4, 10-3 M) dose-dependently inhibited maximal contraction responses induced by acetylcholine and electrical field stimulation. When omeprazole (5x10-4 M) was applied in combination with NSC23766, it caused a significant increase in ACh and EFS-induced responses compared to the NSC23766 alone group. Conclusion: These results show that omeoprazole inhibits contractions in isolated rat detrusor muscle through blockade of rac-1 pathway. Keywords: Detrusor Muscle, Omeprazole, Rac-1 Pathway, Rat

Vinpocetine Ameliorates Metabolic-Syndrome-Associated Bladder Overactivity in Fructose-Fed Rats by Restoring Succinate-Modulated cAMP Levels and Exerting Anti-Inflammatory Effects in the Bladder Detrusor Muscle

Succinate and its receptor, the G protein-coupled receptor 91 (GPR91), have pathological implications in metabolic syndrome (MetS) and its associated bladder dysfunction, particularly in decreasing bladder cAMP levels and promoting proinflammation. Using fructose-fed rats (FFRs), a rat model of MetS, we investigate the effects of vinpocetine (a phosphodiesterase-1 inhibitor) and celecoxib (a selective cyclooxygenase-2 inhibitor) on MetS-associated bladder overactivity. Phenotypes of the overactive bladder, including increased micturition frequency and a shortened intercontractile interval in cystometry, were observed in FFRs, together with elevated succinate levels in the liver and serum and the downregulation of GPR91 in the liver and urinary bladder. Treatments with vinpocetine and celecoxib improved tissue fibrosis and ameliorated the overexpression of the inflammatory cytokines, such as IL-1β, in the liver and bladder. In bladder organ bath studies, vinpocetine, but not celecoxib, treatment restored the contraction and relaxation responses of the detrusor muscle strip in response to KCl, carbachol, and forskolin stimulation. At a molecular level, vinpocetine and celecoxib treatments modulated the downstream messengers of GPR91 (i.e., ERK1/2 and JNK), suppressed NF-κB and IL-1β expressions in the bladder, and prevented the fibrogenesis observed in FFRs. The exogenous application of succinate to a bladder organ bath significantly reduced the forskolin-induced cAMP production by the detrusor muscle, which was notably restored in the presence of vinpocetine. Together, these results suggest that vinpocetine may alleviate the MetS-associated bladder overactivity by restoring the succinate-modulated detrusor cAMP production and exerting the anti-inflammatory effects in the bladder detrusor muscle.

Development and Validation of a UPLC Method for Determination of Mirabegron in Tablet Dosage Forms

Mirabegron is a drug that is used to treat an overactive bladder. Mirabegron activates the β3 adrenergic receptor in the bladder's detrusor muscle, causing muscular relaxation and bladder capacity expansion. A few measurement procedures have been discovered, but they are inconvenient and time-consuming. The current study developed a simple, exact, precise, and practical UPLC technique for determining the amount of Mirabegron in tablet dosage forms. For the verification of Mirabegron, a simple and specific UPLC approach is applied. On an Acquity BEH C18 (50*3.0mm. 1.7m), chromatographic separation was achieved using a versatile stage containing Potassium di hydrogen phosphate: Methanol(70:30) v/v with a detection wavelength of 254 nm. Mirabegron (r2 = 0.997) showed linearity in the 50-150 g/ml range. The amount of Mirabegron to be employed by the suggested technique matches the label exactly. The proposed technique was validated according to ICH guidelines and used to ensure that the correct amount of medication was present in the dosage form.

Imatinib Mesylate Reduces Neurotrophic Factors and pERK and pAKT Expression in Urinary Bladder of Female Mice With Cyclophosphamide-Induced Cystitis.

Imatinib mesylate is a tyrosine kinase inhibitor that inhibits platelet-derived growth factor receptor (PDGFR)-α, -β, stem cell factor receptor (c-KIT), and BCR-ABL. PDGFRα is expressed in a subset of interstitial cells in the lamina propria (LP) and detrusor muscle of the urinary bladder. PDGFRα + interstitial cells may contribute to bladder dysfunction conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) or overactive bladder (OAB). We have previously demonstrated that imatinib prevention via oral gavage or treatment via intravesical infusion improves urinary bladder function in mice with acute (4 hour, h) cyclophosphamide (CYP)-induced cystitis. Here, we investigate potential underlying mechanisms mediating the bladder functional improvement by imatinib using a prevention or treatment experimental design. Using qRT-PCR and ELISAs, we examined inflammatory mediators (NGF, VEGF, BDNF, CCL2, IL-6) previously shown to affect bladder function in CYP-induced cystitis. We also examined the distribution of phosphorylated (p) ERK and pAKT expression in the LP with immunohistochemistry. Imatinib prevention significantly (0.0001 ≤ p ≤ 0.05) reduced expression for all mediators examined except NGF, whereas imatinib treatment was without effect. Imatinib prevention and treatment significantly (0.0001 ≤ p ≤ 0.05) reduced pERK and pAKT expression in the upper LP (U. LP) and deeper LP (D. LP) in female mice with 4 h CYP-induced cystitis. Although we have previously demonstrated that imatinib prevention or treatment improves bladder function in mice with cystitis, the current studies suggest that reductions in inflammatory mediators contribute to prevention benefits of imatinib but not the treatment benefits of imatinib. Differential effects of imatinib prevention or treatment on inflammatory mediators may be influenced by the route and frequency of imatinib administration and may also suggest other mechanisms (e.g., changes in transepithelial resistance of the urothelium) through which imatinib may affect urinary bladder function following CYP-induced cystitis.

Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair

IntroductionFetal myelomeningocele (MMC) repair improves lower extremity motor function. We have previously demonstrated that augmentation of fetal MMC repair with placental mesenchymal stromal cells (PMSCs) seeded on extracellular matrix (PMSC-ECM) further improves motor function in the ovine model. However, little progress has been made in improving bowel and bladder function, with many patients suffering from neurogenic bowel and bladder. We hypothesized that fetal MMC repair with PMSC-ECM would also improve bowel and bladder function. MethodsMMC defects were surgically created in twelve ovine fetuses at median gestational age (GA) 73 days, followed by defect repair at GA101 with PMSC-ECM. Fetuses were delivered at GA141. Primary bladder function outcomes were voiding posture and void volumes. Primary bowel function outcome was anorectal manometry findings including resting anal pressure and presence of rectoanal inhibitory reflex (RAIR). Secondary outcomes were anorectal and bladder detrusor muscle thickness. PMSC-ECM lambs were compared to normal lambs (n = 3). ResultsEighty percent of PMSC-ECM lambs displayed normal voiding posture compared to 100% of normal lambs (p = 1). Void volumes were similar (PMSC-ECM 6.1 ml/kg vs. normal 8.8 ml/kg, p = 0.4). Resting mean anal pressures were similar between cohorts (27.0 mmHg PMSC-ECM vs. normal 23.5 mmHg, p = 0.57). RAIR was present in 3/5 PMSC-ECM lambs that underwent anorectal manometry and all normal lambs (p = 0.46). Thicknesses of anal sphincter complex, rectal wall muscles, and bladder detrusor muscles were similar between cohorts. ConclusionOvine fetal MMC repair augmented with PMSC-ECM results in near-normal bowel and bladder function. Further work is needed to evaluate these outcomes in human patients.

The effect of vitamin D deficiency and supplementation on urinary incontinence: scoping review.

Vitamin D receptors are found in skeletal and smooth muscle cells throughout the body, specifically in the bladder detrusor muscle. We reviewed the current literature on the association between vitamin D deficiency and urinary incontinence (UI), and whether vitamin D supplementation plays a role in the treatment of UI symptoms. We performed a scoping review of all available studies. PubMed, Google Scholar, and PEDro databases were searched from inception until August 2020 with the keywords "urinary incontinence," "pelvic floor disorders," "lower urinary tract symptoms," "overactive bladder," and various terms for vitamin D. No language restrictions were imposed. The reference lists of all retrieved articles were also searched. The search revealed 12 studies of different research methodologies after elimination. In 6 out of the 7 cross-sectional studies reviewed, a significant association between vitamin D deficiency or insufficiency and the onset and severity of UI was found. In 2 out of the 3 prospective studies included, no association between vitamin D intake and UI was found; however, both randomized controlled trials that were reviewed found that vitamin D supplementation is effective for the treatment of UI. The existing literature supports an association between low levels of serum vitamin D and UI. Initial evidence regarding the effect of vitamin D supplementation on UI is accumulating, yet additional, comprehensive research is warranted to establish these findings.

Effect of Electroacupuncture on Bladder Dysfunction via Regulation of MLC and MLCK Phosphorylation in a Rat Model of Type 2 Diabetes Mellitus

Previous studies observed have reported that electroacupuncture (EA) is effective in relieving diabetic bladder dysfunction (DBD); however, little is known about the mechanism. Therefore, we explored the effects and mechanisms of EA on DBD in streptozotocin–high-fat diet- (STZ–HFD-) induced diabetic rats. The Sprague-Dawley male rats were divided randomly into four groups: normal group, diabetes mellitus group (DM group), DM with EA treatment group (EA group), and DM with sham EA treatment group (sham EA group). After 8 weeks of EA treatment, the body weight, serum glucose, bladder weight, and cystometrogram were evaluated. The bladder wall thickness was examined by abdominal ultrasound imaging. After the transabdominal ultrasound measurements, hematoxylin-eosin (HE) staining was used to observe the bladder mucosa layer. The bladder detrusor smooth muscle cells (SMCs) and fibroblasts were observed under transmission electron microscopy (TEM). The phospho-myosin light chain (p-MLC), phospho-myosin light chain kinase (p-MLCK), and phospho-myosin phosphatase target subunit 1 (p-MYPT1) levels in the bladder were examined using Western blot. The bladder weight, serum glucose, bladder wall thickness, volume threshold for micturition, and postvoid residual (PVR) volume in the diabetic rats were significantly higher than those in the control animals. EA treatment significantly reduced the bladder weight, bladder wall thickness, volume threshold for micturition, and PVR volume in diabetic rats. EA caused a significant increase in the MLC dephosphorylation and MLCK phosphorylation levels in the group compared to the sham EA and model groups. EA reduced the infiltration of inflammatory cells in the bladder mucosa layer of diabetic rats. In addition, EA repaired the damaged bladder detrusor muscle of diabetic rats by reducing mitochondrial damage of the SMCs and fibroblasts. Therefore, EA could reduce the bladder hypertrophy to ameliorate DBD by reversing the impairment in the mucosa layer and detrusor SMCs, which might be mainly mediated by the regulation of p-MLC and p-MLCK levels.

The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1β, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T–H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.

Urinary Retention Following Inguinal Herniorrhaphy: Role of Neuromuscular Blockade Reversal.

Nondepolarizing neuromuscular blockade is reversed with neostigmine/glycopyrrolate or sugammadex. Anticholinergic glycopyrrolate decreases bladder detrusor muscle contractility, potentially leading to postoperative urinary retention (POUR). POUR commonly complicates inguinal herniorrhaphy. In this study we assess association between reversal technique and POUR. Records of adult patients undergoing unilateral inguinal herniorrhaphy with neuromuscular blockade from January 2013 to September 2020 were reviewed for POUR (unplanned postoperative insertion of urinary catheter). A propensity-adjusted analysis was performed to assess POUR in neostigmine/glycopyrrolate versus sugammadex using inverse probability of treatment weighting (IPTW) to adjust for potential confounding. We identified 181 patients who underwent herniorrhaphy with amnio-steroidal neuromuscular blockers, 75 (41.4%) who received sugammadex and 106 (58.6%) neostigmine/glycopyrrolate. Compared with sugammadex, neostigmine/glycopyrrolate group had longer surgical course [unweighted standardized difference (USTD)=0.38, P=0.004], received more intraoperative opioids (USTD=0.704, P<0.001), more often performed via laparoscopic approach (USTD=0.407, P=0.012), and less often with periprocedural urinary catheter insertion (USTD=0.452, P=0.003). POUR was observed in 2 (3%) of patients in the sugammadex group, and 16 (15%) in neostigmine/glycopyrrolate [unadjusted odds ratio (OR)=0.15; 95% confidence interval (CI): 0.03-0.69; P=0.015, and IPTW OR=0.13; 95% CI: 0.03-0.64; P=0.012]. Results remained similar with further analysis adjusted for opioid administration in the postanesthesia care unit (adjusted IPTW OR=0.18; 95% CI: 0.04-0.88; P=0.034). Of the POUR patients, 9 required unplanned overnight admission and 4 emergency room visit. These results suggest that neuromuscular blockade reversal with sugammadex is associated with lower rates of POUR following unilateral inguinal herniorrhaphy. Our results need to be reconfirmed in a randomized prospective study.

A pilot study of bladder voiding with real-time MRI and computational fluid dynamics.

Lower urinary track symptoms (LUTS) affect many older adults. Multi-channel urodynamic studies provide information about bladder pressure and urinary flow but offer little insight into changes in bladder anatomy and detrusor muscle function. Here we present a novel method for real time MRI during bladder voiding. This was performed in a small cohort of healthy men and men with benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) to demonstrate proof of principle; The MRI urodynamic protocol was successfully implemented, and bladder wall displacement and urine flow dynamics were calculated. Displacement analysis on healthy controls showed the greatest bladder wall displacement in the dome of the bladder while men with BPH/LUTS exhibited decreased and asymmetric bladder wall motion. Computational fluid dynamics of voiding showed men with BPH/LUTS had larger recirculation regions in the bladder. This study demonstrates the feasibility of performing MRI voiding studies and their potential to provide new insight into lower urinary tract function in health and disease.

Therapeutic effects and modulatory mechanism of Alpiniae oxyphyllae Fructus in chronic intermittent hypoxia induced enuresis in rats.

The objective of this study was to explore the effect of Alpiniae oxyphyllae Fructus (AOF) on a rat model of chronic intermittent hypoxia (CIH)-induced enuresis. Findings of this study may help identify therapeutic targets in children with nocturnal enuresis (NE). Female rats were randomly divided into a control group (saline gavage, 4 weeks of normal air), CIH group (saline gavage, 4 weeks of CIH), and AOF group (AOF gavage, 4 weeks of CIH). The variables measured in this study included water intake, urine output, bladder leak point pressure (BLPP), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. The expression levels of the purinergic P2X3 receptor, muscarinic M3 receptor, and ß3-adrenergic receptor (ß3-AR) in the bladder were also measured. The bladder was subjected to haematoxylin and eosin (HE) and Weigert staining, and histological changes were observed under a light microscope to evaluate the morphological changes in the bladder in each group. Compared with the control group, urine output was increased, and the BLPP was decreased in the CIH group, but AOF administration decreased urine output and increased BLPP. In addition, the serum MDA level increased and the SOD activity decreased in the CIH group compared with the control group. Administration of AOF decreased the MDA level and increased the SOD activity. Additionally, compared with the control group, HE and Weigert staining in the CIH group showed that the bladder detrusor muscle bundles were disordered and loose, some muscle bundles were broken, the content of collagen fibres in the gap was reduced, and the gap was significantly widened. However, following the administration of AOF, the bladder detrusor muscle bundles were neatly arranged, and the content of collagen fibres in the gap was increased. Furthermore, compared with the control group, the purinergic P2X3 receptor and muscarinic M3 receptor were expressed at higher levels, and ß3-AR was expressed at lower levels in the CIH group, but AOF administration decreased the expression of the purinergic P2X3 receptor and muscarinic M3 receptor and increased the expression of the ß3-AR. AOF improves enuresis by inhibiting oxidative stress and regulating the expression of the purinergic P2X3 receptor, muscarinic M3 receptor, and ß3 adrenergic receptor.