Detrusor Contraction Research Articles

The urethra in continence and sensation: Neural aspects of urethral function.

Traditionally, the urethra has been considered a mere conduit to guide urine from the bladder to the external side of the body. Building evidence indicates that the urethra may directly influence bladder function via mechanisms restricted to the lower urinary tract (LUT). Here, we discuss the tissue arrangement of the urethra and addressed the contribution of new paraneuronal cells to LUT function. We also briefly reviewed two frequent LUT pathologies associated with urethral dysfunction. Continence depends on an intact and functional urethral sphincter, composed of smooth, and striated muscle fibers and regulated by somatic and autonomic fibers. Recent studies suggest the existence of an urethro-vesical reflex that also contributes to normal LUT function. Indeed, the urethral lumen is lined by a specialized epithelium, the urothelium, in the proximal urethra. In this region, recent evidence demonstrates the presence of specific paraneuronal cells, expressing the neurotransmitters acetylcholine and serotonin. These cells are in close proximity of nerve fibers coursing in the lamina propria and are able to release neurotransmitters and rapidly induce detrusor contractions, supporting the existence of an urethro-vesical crosstalk. The mechanism underlying the fast communication between the urethra and thebladder are beginning to be understood and should involve the interaction between specificepithelial cells and fibres innervating the urethral wall. It is likely that this reflex should bealtered in pathological conditions, becoming an attractive therapeutic target.

Urodynamic evaluation of patients with localized prostate cancer before and 4\xa0months after robotic radical prostatectomy

Radical prostatectomy can alter the anatomy of the urinary bladder. We aimed to evaluate bladder function before and 4 months after radical prostatectomy using the urodynamic test and overactive bladder (OAB) symptom score. Among 70 prospectively enrolled patients, 61 patients completed the study. In the urodynamic test, bladder capacity and compliance did not change, the frequency of involuntary detrusor contraction decreased, the maximum flow rate and bladder outlet obstruction index improved, and the maximum urethral closure pressure (MUCP) deteriorated. Further evaluation of urodynamic parameters according to changes in symptoms was made. Although change in bladder compliance was correlated with changes in OAB symptoms, not the relative change of bladder compliance but the relative change in the MUCP was reliable factor when OAB symptoms were deteriorated. In general, prostatectomy did not deteriorate the condition of the detrusor; rather, change in the MUCP could be responsible for postprostatectomy OAB.

Effects of High Salt Intake on Detrusor Muscle Contraction in Dahl Salt-Sensitive Rats.

High salt intake has been reported as a risk factor for urinary storage symptoms. However, the association between high salt intake and detrusor muscle contraction is not clear. Therefore, we investigated the effects of high salt intake on the components of detrusor muscle contraction in rats. Six-week-old male Dahl salt-resistant (DR; n = 5) and Dahl salt-sensitive (DS; n = 5) rats were fed a high salt (8% NaCl) diet for one week. The contractile responses of the detrusor muscle to the cumulative administration of carbachol and electrical field stimulation (EFS) with and without suramin and atropine were evaluated via isometric tension study. The concentration–response curves of carbachol were shifted more to the left in the DS group than those in the DR group. Contractile responses to EFS were more enhanced in the DS group than those in the DR group (p < 0.05). Cholinergic component-induced responses were more enhanced in the DS group than those in the DR group (p < 0.05). High salt intake might cause urinary storage symptoms via abnormalities in detrusor muscle contraction and the enhancement of cholinergic signals. Excessive salt intake should be avoided to preserve bladder function.

The Sustained Therapeutic Effects of Percutaneous Posterior Tibial Nerve Stimulation in the Treatment of Neurogenic Lower Urinary Tract Symptoms in Patients with Parkinson's Disease: 24-months Clinical and Urodynamic Results

To determine the sustained therapeutic effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment in Parkinson's disease patients with detrusor activity during 24 months. After 12 weeks therapy, PTNS was applied at 14-day intervals for 3 months, 21-day intervals for 3 months and 28-day intervals through 24 months. The patients completed a 3-day voiding diary and ICIQ-SF, OAB-V8, OAB-q SF questionnaires at 3rd, 6th, 9th,12th and 24th month. A total of 76 patients were enrolled in the study. Of these 44 (57.9%) were men and 32 (42.1%) women. The differences of compared parameters at baseline and at the end of 24 months were as follows; daytime frequency decreased by 4.6 voids daily, urge incontinence decreased by 4.2 episodes daily, urgency episodes decreased by 6.2 episodes daily, nocturia decreased by 2.4 voids (P <.001) and voided volume improved by a mean of 71.4 cc (P <.05). When compared with baseline significant improvements were seen in the volume at the first involuntary detrusor contraction (1st IDCV), maximum cystometric capacity (MCC), maximal detrusor pressure at first involuntary detrusor contraction (1st IDC Pdetmax), maximal detrusor pressure at MCC (MCC Pdetmax), detrusor pressure at maximal flow (PdetQmax) and post-void residual volume (PVR) after PTNS treatment at 3, 12, 24 months (P <.001 for each) except maximal flow rate (Qmax) value (P ˃.05). These results have demonstrated the significant improvements both on voiding and urodynamic parameters under PTNS treatment with a tapering protocol for during 24-months in Parkinson's disease with detrusor activity.

Inhibition of LIM kinase reduces contraction and proliferation in bladder smooth muscle

Overactive bladder (OAB) is the most bothersome symptom in lower urinary tract symptoms (LUTS). Current pharmacologic treatment aims to inhibit detrusor contraction; however, shows unsatisfied efficacy and high discontinuation rate. LIM kinases (LIMKs) promote smooth muscle contraction in the prostate; however, their function in the bladder smooth muscle remains unclear. Here, we studied effects of the LIMK inhibitors on bladder smooth muscle contraction and proliferation both in vitro and in vivo experiments. Bladder expressions of LIMKs are elevated in OAB rat detrusor tissues. Two LIMK inhibitors, SR7826 and LIMKi3, inhibit contraction of human detrusor strip, and cause actin filament breakdown, as well as cell proliferation reduction in cultured human bladder smooth muscle cells (HBSMCs), paralleled by reduced cofilin phosphorylation. Silencing of LIMK1 and LIMK2 in HBSMCs resulted in breakdown of actin filaments and decreased cell proliferation. Treatment with SR7826 or LIMKi3 decreased micturition frequency and bladder detrusor hypertrophy in rats with bladder outlet obstruction. Our study suggests that LIMKs may promote contraction and proliferation in the bladder smooth muscle, which could be inhibited by small molecule LIMK inhibitors. LIMK inhibitors could be a potential therapeutic strategy for OAB- related LUTS.

Beyond gait and balance: urinary and bowel dysfunction in X-linked adrenoleukodystrophy

ObjectiveTo characterize the prevalence, onset, and burden of urinary and bowel dysfunction in adult patients with adrenoleukodystrophy (ALD) and to evaluate any sex differences in symptom presentation.MethodsIn this retrospective and prospective study, we performed medical record review (n = 103), analyzed the results of clinically indicated urodynamic testing (n = 11), and developed and distributed a symptom and quality of life (QOL) survey (n = 59).ResultsUrinary and bowel symptoms are highly prevalent in both males (75.0%) and females (78.8%) in this population, most commonly urinary urgency, often leading to incontinence. Time to onset of first urinary or bowel symptom occurs approximately a decade earlier in males. Seventy-two percent of symptomatic patients report a limitation to QOL. Urodynamic evaluation provides evidence of three distinct mechanisms underlying lower urinary tract dysfunction: involuntary detrusor contractions (indicating uncontrolled neuronal stimulation with or without leakage), motor underactivity of the bladder, and asynergy between detrusor contraction and sphincter relaxation.ConclusionsBeyond gait and balance difficulties, urinary and bowel symptoms are common in adults with ALD and impair QOL. Males are affected at a younger age but both sexes experience a higher symptom burden with age. As this population also experiences gait and balance impairment, patients with ALD are more vulnerable to urinary urgency leading to incontinence. Urodynamic evaluation may help better elucidate the pathophysiologic mechanisms underlying neurogenic lower urinary tract dysfunction, which can allow more targeted treatment.

Using Physical Factor Therapy for Postoperative Patients with Cerebral Apoplexy Voiding Dysfunction: A Case Study

Objective: We introduce and analyze by physical factors treatment case the method and effect of urinary retention after stroke, li xx hospital diagnosis: patients with cerebral hemorrhage postoperative recovery, on the left side of the limb dysfunction, urinary bladder sensitivity is poorer, lack of detrusor activity, urethral sphincter muscle tension increased, urination disorders, urinary retention. Treatment methods: Using electrical therapeutic apparatus, electrodes cross placed in the lower abdomen in patients with bladder section. Using percutaneous nerve electrical stimulation, placed therapeutic apparatus is the cathode respectively in patients with the third sacral vertebral and bladder reflex zone, set the treatment frequency is 120 hz, voltage range of 20 ~ 26 v. Using shortwave treatment, set the short-wave frequency therapy apparatus 10 w, before and after the placement of electrodes, to help urethral sphincter muscle tension relaxed, eliminate urinary tract inflammation and edema. Results: By interfering with the treatment, percutaneous neuromuscular electrical stimulation (TENS) and short wave 15 days after treatment, patients can feel obviously can urinate and pa ontaneously 300 ml urine volume. Conclusion: interference electric treatment can stimulate the detrusor contraction, short-wave can improve urethral sphincter muscle tension, Percutaneous neuromuscular electrical stimulation therapy can excitement parasympathetic promote bladder function, improve urinary retention in patients with quality of life.

Gabapentin add-on therapy for patients with spinal cord injury associated neurogenic overactive detrusors that are unresponsive to combined anticholinergic and beta-3 adrenergic therapy.

IntroductionSpinal cord injury is a major cause of lifelong morbidity and functional micturition problems. Some patients are refractory to the available therapeutics, even when used in combination. In this paper we report our results of using gabapentin as an add-on treatment in refractory overactive detrusor cases secondary to spinal cord injury.Material and methodsA total of 27 patients who had a spinal cord injury between the levels of the second thoracic and fourth lumbar vertebrae and had an overactive detrusor in urodynamic studies were included in this retrospective study. The patients were selected due to the fact that they also had not responded to a combination of an anticholinergic and mirabegron and had neuropathic pain. Gabapentin treatment was added to the previous therapy. Demographics, previous treatments, chronic conditions, urodynamic findings, clinical and urodynamic responses are reported in this paper.ResultsWe observed a response to treatment in the urodynamic studies of 11 patients (40.17%), in terms of decreased detrusor contractions, maximal detrusor pressure, and the number of incontinence episodes. Sixteen patients did not respond to the gabapentin add-on therapy and were referred for Botulinum toxin injections to the bladder.ConclusionsGabapentin add-on therapy can be considered as a third or further option, before Botulinum toxin injection, for patients with neurogenic overactive detrusor who did not respond to the combination of anticholinergics and mirabegron. The approved usage of gabapentin for neurogenic pain justifies its usage in this area. In our selected patient group, who had not responded to the combination therapy, we observed a clinical benefit in one-third of the patients.

Impairment of AMPK-α2 augments detrusor contractions in bladder ischemia.

PurposeIschemia disrupts cellular energy homeostasis. Adenosine monophosphate-activated protein kinase alpha-2 (AMPK-α2) is a subunit of AMPK that senses cellular energy deprivation and signals metabolic stress. Our goal was to examine the expression levels and functional role of AMPK-α2 in bladder ischemia.Materials and MethodsIliac artery atherosclerosis and bladder ischemia were engendered in apolipoprotein E knockout rats by partial arterial endothelial denudation using a balloon catheter. After eight weeks, total and phosphorylated AMPK-α2 expression was analyzed by western blotting. Structural integrity of AMPK-α2 protein was assessed by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Functional role of AMPK-α2 was examined by treating animals with the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D ribofuranoside (AICAR). Tissue contractility was measured in the organ bath and bladder nerve density was examined by immunostaining.ResultsTotal AMPK-α2 expression increased in bladder ischemia, while phosphorylated AMPK-α2 was significantly downregulated. LC-MS/MS suggested post-translational modification of AMPK-α2 functional domains including phosphorylation sites, suggesting accumulation of catalytically inactive AMPK-α2 in bladder ischemia. Treatment of rats with AICAR diminished the force of overactive detrusor contractions and increased bladder capacity but did not have a significant effect on the frequency of bladder contractions. AICAR diminished contractile reactivity of ischemic tissues in the organ bath and prevented loss of nerve fibers in bladder ischemia.ConclusionsIschemia induces post-translational modification of AMPK-α2 protein. Impairment of AMPK-α2 may contribute to overactive detrusor contractions and loss of nerve fibers in bladder ischemia. AMPK activators may have therapeutic potential against detrusor overactivity and neurodegeneration in bladder conditions involving ischemia.

OnabotulinumtoxinA for the treatment of neurogenic detrusor overactivity in children.

AimsThis study evaluated whether one (or more) of three doses of onabotulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children.MethodsThis was a 48‐week prospective, multicenter, randomized, double‐blind study in children (aged 5–17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes. Secondary endpoints: change from baseline in urine volume at first morning catheterization, urodynamic measures, and positive response on the treatment benefit scale. Safety was also assessed.ResultsThere was a similar reduction in urinary incontinence from baseline to Week 6 for all doses (−1.3 episodes/day). Most patients reported positive responses on the treatment benefit scale (75.0%−80.5%). From baseline to Week 6, increases were observed in urine volume at first morning clean intermittent catheterization (50 U, 21.9 ml; 100 U, 34.9 ml; 200 U, 87.5 ml; p = 0.0055, 200 U vs. 50 U) and in maximum cystometric capacity (range 48.6−63.6 ml) and decreases in maximum detrusor pressure during the storage phase (50 U, −12.9; 100 U, −20.1; 200 U, −27.3 cmH2O; p = 0.0157, 200 U vs. 50 U). The proportion of patients experiencing involuntary detrusor contractions dropped from baseline (50 U, 94.4%; 100 U, 88.1%; 200 U, 92.6%) to Week 6 (50 U, 61.8%; 100 U, 44.7%; 200 U, 46.4%). Safety was similar across doses; urinary tract infection was most frequent.ConclusionsOnabotulinumtoxinA was well tolerated and effective for the treatment of NDO in children; 200 U showed greater efficacy in reducing bladder pressure and increasing bladder capacity.

Short-term reproducibility of cystometry in multiple sclerosis patients

To assess the reproducibility of detrusor activity cystometric pattern in multiple sclerosis (MS) patients, which is poorly documented in the medical literature, by means of successive filling. We conducted a prospective study in MS patients; cystometry was repeated twice at 5minutes of interval if a detrusor overactivity before 300mL of filling was observed. Thus, 3 successive cystometries were analysed. The following characteristics were recorded: detrusor maximum pressure (Pmax), volume at the first involuntary detrusor contraction (IDC), maximum cystometric capacity (MCC), pressure at the first IDC, the existence of an overactive detrusor classified as phasic or terminal. We included 31 patients (19 women and 12 men); only 6 patients were naïve-treatment, the mean EDSS was: 5.3 (±1.6) and the mean age was 48.4 (±12.5) years. All the patients had an overactive detrusor for each cystometry. The reproducibility was good for all the parameters (range ICC between 0.7 and 0.83). Quantitative and qualitative cystometric data have a good reproducibility in MS patients with detrusor overactivity before 300mL of filling. 3.

An inhibitory effect of Berberine from herbal Coptis chinensis Franch on rat detrusor contraction in benign prostatic hyperplasia associated with lower urinary tract symptoms

Ethnopharmacological relevanceCoptis chinensis Franch (CCF), also known as Huang Lian in China, is a traditional Chinese medicine that commonly used for more than 2000 years. Clinically, CCF often used as anti-inflammatory, immune regulation and other effects. It has been reported that the decoction containing CCF can be used for the treatment of benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS).Aim of the study: This research aims to investigate the effect of CCF on inhibition of BPH development in vivo and in vitro, and further identify the active compound (s) and the possible mechanism involved in BPH-related bladder dysfunction. Materials and methodsOestrodial/testosterone-induced BPH rat model was established as the in vivo model. The prostate index (PI) was calculated, the pathogenesis was analyzed and the micturition parameters were determined in the shamed-operated, BPH model and BPH + CCF groups after 4-week administration. The tension in detrusor strips was then assessed upon KCl or ACh stimulation with or without incubation of CCF or active compounds. To further investigate the signaling involved, rat detrusor cells were cultured as the in vitro models, the instantaneous calcium influx was measured and the ROCK-1 expression was detected. ResultsIncreased PI value and the aggravated prostatic pathology were observed with voiding dysfunction in BPH rats, which were significantly blocked by oral CCF taken. ACh or KCl-induced contractile responses in detrusor strips were significantly inhibited and the micturition parameters were improved when incubation with CCF or its active compounds such as berberine. Both CCF and berberine suppressed the cellular calcium influx and ROCK-1 expression upon ACh stimulation, demonstrating that berberine was one of the active compounds that contributed to CCF-improved micturition symptoms and function. ConclusionsTaken together, our findings give evidence that CCF and its active compound berberine inhibited BPH and bladder dysfunction via Ca2+ and ROCK signaling, supporting their clinical use for BPH and BPH-related LUTS treatment.

Comparison of intravesical instillation of hyaluronic acid with intradetrusor botulinum toxin A injection or cystoscopic hydrodistention for ketamine-associated cystitis.

ObjectiveThis study aimed to compare the therapeutic effect of intravesical instillation hyaluronic acid with intradetrusor botulinum toxin A (BTX-A) injection or cystoscopic hydrodistention for ketamine-associated cystitis.MethodsThirty-six patients were evenly randomly divided into the BTX-A group or the hydrodistention group. Patients received 200 U BTX-A detrusor injections in the BTX-A group and cystoscopic hydrodistention in the hydrodistention group. Intravesical instillation of hyaluronic acid was administrated in both groups for eight times. Patients with involuntary detrusor contraction were divided into the persistent involuntary detrusor contraction group and resolved involuntary detrusor contraction group after treatment in 6 months. The predictors of persistent involuntary detrusor contraction were analyzed.ResultsTwelve months after treatment, the daytime frequency, Interstitial Cystitis Symptom Index, maximal capacity, and maximal cystometric capacity in the BTX-A group were significantly better than those in the hydrodistention group. Patients with resolution of involuntary detrusor contraction had a significantly shorter duration of ketamine, lower amount of fibrosis in pathology, and higher maximal capacity than those with persistent involuntary detrusor contraction 6 months after therapy.ConclusionIntravesical instillation of hyaluronic acid with intradetrusor BTX-A injection appears to be a preferable option for long-term effectiveness compared with cystoscopic hydrodistention.

Sexual dimorphism of detrusor function demonstrated by urodynamic studies in rhesus macaques

The lower urinary tract (LUT) and micturition reflexes are sexually dimorphic across mammals. Sex as a biological variable is also of critical importance for the development and translation of new medical treatments and therapeutics interventions affecting pelvic organs, including the LUT. However, studies of LUT function with comparisons between the sexes have remained sparse, especially for larger mammals. Detrusor function was investigated by filling cystometry and pressure flow studies in 16 male and 22 female rhesus macaques. By filling cystometry, male subjects exhibited a significantly larger bladder capacity and compliance compared to females. Pressure flow studies showed a significantly higher bladder pressure at voiding onset, peak pressure, and elevation in detrusor-activated bladder pressure from the end of bladder filling to peak pressure in the male subjects. The activation of reflex micturition, with associated detrusor contractions, resulted in voiding in a significantly larger proportion of female compared to male subjects. A higher urethral outlet resistance is suggested in the male subjects. We conclude that sexual dimorphism of detrusor function is prominent in rhesus macaques, shares many features with the human, and merits consideration in translational and pre-clinical research studies of micturition and LUT function in non-human primates.

Understanding the mechanics of closure is key to optimal midurethral sling technique

The animal experiments and prototype midurethral sling operations demonstrated that the sling provided new collagen to reinforce weak pubourethral ligaments (PUL). The now strengthened PULs were able to restore the contractile power of the 3 oppositely-acting directional closure forces. By contraction, these three forces exponentially altered the intraurethral resistance to flow when they closed the urethra to sustain continence. Relaxation of the forward force allowed the two posterior forces to uninhibitedly open the posterior urethral wall just prior to detrusor contraction, to facilitate evacuation of urine. The aim of this work is to examine the mechanics of the component anatomical structures which contribute to these functions, to analyse how subtle details impact on the actual surgical technique of the midurethral sling operations to optimize success, contribute to complications and how to prevent and fix them.

Low energy shock wave-delivered intravesical botulinum neurotoxin-A potentiates antioxidant genes and inhibits proinflammatory cytokines in rat model of overactive bladder.

To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.

Association of Detrusor Muscular Activity With the Outcome of Transurethral Resection of Prostate in Patients With Severity of Bladder Outflow Obstruction

Objective: To evaluate the association of detrusor muscular activity with outcome of TURP in patients with severity of bladder outflow obstruction. Methods: This is a hospital based cross sectional study conducted in the Department of Urology of Dhaka Medical College Hospital, Dhaka.Elderly male patients having lower urinary tract symptoms (IPSS=20-35) with no retention (non-catheterized patient), who attended in Dhaka Medical College Hospital, were included in the study. A total of 73 patients meeting the enrollment criteria were included in the study. They were evaluated by history, physical examination including DRE and necessary investigations to identify the potential candidates for TURP. Then the potential participants were counseled for Urodynamic study. All patients underwent TURP by expert surgeon. Three months after TURP, repeat Urodynamic study was done and the results were compared to see the outcome. Afterward the data were plotted for the clarification of detrusor contractility at three levels: normal detrusor contractility (voiding pressure 40-60cm of water), detrusor over activity (voiding pressure &gt;60cm of water) and detrusor under activity (voiding pressure &lt;40 cm of water). According to the provisional ICS nomogram for the analysis of voiding, patients were divided into three classes. In BOO Index(PdetQmax-2Qmax),obstructed(BOOI &gt; 40); equivocal(BOOI=20-40);Unobstructed(BOOId” 20) are taken into consideration. The test statistic used to analyze the data was descriptive statistics and ANOVA test. The level of significance was set at 0.05 and P&lt;O.05 was considered significant. Results: Out of 73 patients 8 didn’t attend follow up session and hence excluded keeping 65 for final analysis. The mean age was 66.3 ± 9.7 years (50- 87 years) .Detrusor over activity was present in 13(20%), normal detrusor contractility was observed in 46(70.8%) and weak contractility in 6(9.2%). Peak urinary flow rate was almost similar among patients of different groups. However, voided volume and residual volume were lowest in overactive group and highest in underactive group, while normal group was in between two (p = 0.007 and p = 0.046 respectively). Maximum urinary flow rate and voided urine between patients of moderate and severe bladder outlet obstruction were almost comparable (p =0.120 and p = 0.270 respectively). However, residual urine volume was much higher in the patients of moderate BOO than that in severe BOO (p = 0.001).The patients of OAB experienced a significant improvement in percentage of reduction of residual urine volume compared to normal and underactive bladder (p = 0.002), However, there were no significant difference among the patients with overactive, normal and underactive bladder with respect to peak urinary flow rate and voided urine volume (p = 0.499 and p = 0.847 respectively). Conclusion: TURP is an effective surgical procedure for treatment of BPH, especially for patients with severe degree of BOO with normal or overactive detrusor contraction. Bangladesh Journal of Urology, Vol. 18, No. 2, July 2015 p.56-61

Therapeutic Efficacy of Human Embryonic Stem Cell-Derived Multipotent Stem/Stromal Cells in Diabetic Detrusor Underactivity: A Preclinical Study.

Mesenchymal stem/stromal cell (MSC) therapy is a promising approach for treatment of as yet incurable detrusor underactivity (DUA), which is characterized by decreased detrusor contraction strength and/or duration, leading to prolonged bladder emptying. In the present study, we demonstrated the therapeutic potential of human embryonic stem cell (ESC)-derived multipotent MSCs (M-MSCs) in a diabetic rat model of DUA. Diabetes mellitus (DM) was induced by intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) into 8-week-old female Sprague-Dawley rats. Three weeks later, various doses of M-MSCs (0.25, 0.5, and 1 × 106 cells) or an equivalent volume of PBS were injected into the outer layer of the bladder. Awake cystometry, organ bath, histological, and gene expression analyses were evaluated 1 week (short-term) or 2 and 4 weeks (long-term) after M-MSC transplantation. STZ-induced diabetic rats developed DUA, including phenotypes with significantly longer micturition intervals, increased residual urine amounts and bladder capacity, decreased micturition pressure on awake cystometry, and contractile responses to various stimuli in organ bath studies. Muscle degeneration, mast cell infiltration, fibrosis, and apoptosis were present in the bladders of DM animals. A single local transplantation of M-MSCs ameliorated DUA bladder pathology, including functional changes and histological evaluation, and caused few adverse outcomes. Immunostaining and gene expression analysis revealed that the transplanted M-MSCs supported myogenic restoration primarily by engrafting into bladder tissue via pericytes, and subsequently exerting paracrine effects to prevent apoptotic cell death in bladder tissue. The therapeutic efficacy of M-MSCs was superior to that of human umbilical cord-derived MSCs at the early time point (1 week). However, the difference in efficacy between M-MSCs and human umbilical cord-derived MSCs was statistically insignificant at the later time points (2 and 4 weeks). Collectively, the present study provides the first evidence for improved therapeutic efficacy of a human ESC derivative in a preclinical model of DM-associated DUA.

Silodosin improves functional consequences of lower urinary tract obstruction secondary to benign prostate hypertrophy, a proof of concept study in the spontaneously hypertensive rat supplemented with testosterone

BackgroundThe main purpose of this study is to investigate the effect of silodosin on the urodynamic consequences in a previously established model of lower urinary tract symptoms associated with benign prostate hyperplasia, the spontaneously hypertensive rats (SHR) supplemented with testosterone.MethodsThree groups of animals (8-week-old; n = 10/group) were considered: Wistar Kyoto (control) rats (WKY), SHR supplemented with testosterone at 3 mg/kg/day and treated with either vehicle (SHR-T, n = 10) or silodosin at 0.1 mg/kg/day (SHR-T + silodosin, n = 10) by oral gavage for 6 weeks. Cystometry experiments were performed. The bladder was harvested, weighed and paraffin-embedded for morphometric analysis. The prostate was also harvested and weighed.ResultsThe number of animals included in the analysis were n = 10/10 for WKY and n = 7–8/10 for each SHR rats supplemented with testosterone group. SHR-T displayed a significant decrease in the intercontraction interval, infused volume and mean flow rate whereas the frequency of non-voiding contractions was increased. Silodosin improved the voiding behavior of SHR-T by significantly increasing the intercontraction interval, the infused volume and the mean flow rate and decreasing the number of non-voiding contractions. SHR-T displayed a significant increase in prostate and bladder weights and a 15% increase in the detrusor wall area compared to WKY.ConclusionsChronic silodosin treatment relieved storage symptoms in SHR supplemented with testosterone and decreased the frequency of non-voiding detrusor contractions during the filling phase.

Urodynamic efficacy of fesoterodine for the treatment of neurogenic detrusor overactivity and/or low compliance bladder.

ObjectiveTo examine the urodynamic effects of fesoterodine on neurogenic detrusor overactivity and/or low compliance bladder.MethodsA total of 77 patients (52 men, 25 women; aged 61.6 ± 20.3 years) were given fesoterodine 4–8 mg/day and prospectively followed for 12 weeks. The primary end‐point variable was change in the maximum cystometric capacity on urodynamic study. The secondary end‐point was to assess the number of patients whose neurogenic detrusor overactivity disappeared, and the changes in the urodynamic parameters, lower urinary tract symptoms questionnaires and the 3‐day frequency volume chart parameters after the treatment.ResultsA total of 13 patients (16.9%) withdrew because of adverse events (dry mouth or blurred vision), and four patients dropped out for unknown reasons. Finally, 60 patients completed the study. Bladder capacity at first desire to void, maximum cystometric capacity and bladder compliance increased by 29.2 mL, 79.9 mL and 22.2 mL/cm H2O, respectively, showed statistical significance (P = 0.026, P < 0.001 and P < 0.001). Neurogenic detrusor overactivity disappeared in 12 of 51 patients (23.5%), and a significant increase was observed in bladder capacity at first involuntary contraction (P < 0.001), and a significant decrease was observed in maximum detrusor contraction (P < 0.001). In patients with low compliance bladder (with detrusor underactivity without neurogenic detrusor overactivity; n = 9), maximum cystometric capacity and bladder compliance increased significantly (P = 0.003 and P = 0.006, respectively). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire–Short Form, most items of King’s Health Questionnaire, and the number of urgency episodes and leaks in a day decreased significantly after treatment.ConclusionsFesoterodine seems to be a valid treatment option for neurogenic detrusor overactivity and/or low compliance bladder in neurogenic bladder patients.