Bladder Voiding Dysfunction Research Articles

Computational fluid dynamics of bladder voiding using 3D dynamic MRI.

Over the last couple of decades, image-based computational fluid dynamics (CFD) has revolutionized cardiovascular research by uncovering hidden features of wall strain, impact of vortices, and its use in treatment planning, as examples, that were simply not evident in the gold-standard catheterization studies done previously. In the work presented here, we have applied magnetic resonance imaging (MRI)-based CFD to study bladder voiding and to demonstrate the feasibility and potential of this approach. We used 3D dynamic MRI to image the bladder and urethra during voiding. A surface mesh processing tool was developed to process the bladder wall prior to executing a wall-motion driven CFD simulation of the bladder and urethra. The obtained flow rate and pressure were used to calculate urodynamic nomograms, which are currently used in the clinical setting to assess bladder voiding dysfunction. These nomograms concluded that our healthy volunteer has an unobstructed bladder and normal contractility. We calculated the work done to void the bladder and propose this as an additional quantitative metric to comprehensively assess bladder function. Further, we discuss the areas that would improve this relatively new methodology of image-based CFD in urodynamics.

Intermittent Self-catheterization for Bladder Dysfunction After Deep Endometriosis Surgery: Duration and Factors that Might Affect the Recovery Process

ObjectiveTo assess the duration needed for regaining normal bladder voiding function in patients with postoperative bladder dysfunction requiring intermittent self-catheterization after deep endometriosis surgery, and identify risk factors that might affect the recovery process. DesignRetrospective study based on data recorded in a large prospective database. SettingEndometriosis referral center. PatientsFrom September 2018 to June 2022, 1,900 patients underwent excision of deep endometriosis in our center. 61 patients were discharged with recommendation for intermittent self-catheterization and were thus included in the study. InterventionsIntermittent self-catheterization after endometriosis surgery. Measurements and Main Results43 patients (70.5%) stopped self-catheterization during the follow up period. Median follow up was 25 weeks (range, 7 to 223 weeks). Surgery was performed laparoscopically in 48 patients (78.7%) and robotically in 13 (21.3%). 47 patients (77%) had nodules involving the digestive tract, 11 (18%) had urinary tract involvement, 29 had parametrial nodules (47.5%) and 13 (21.3%) had sacral plexus involvement. The probability of bladder voiding function recovery and arrest of self-catheterization was 24.5%, 54%, 59%, 72%, and 77% at 4, 8, 12, 52, and 78 weeks respectively. Cox's multivariate model identified preoperative bladder dysfunction as the only statistically significant independent predictor for arrest of self-catheterization (HR 0.36, 95%CI 0.15-0.83). ConclusionsPatients requiring intermittent self-catheterization for bladder dysfunction after deep endometriosis excision may spontaneously recover bladder function in 77% of cases. Symptoms suggesting preoperative bladder voiding dysfunction should be reviewed before planning surgery, and patients should be informed of the higher postoperative risk of long-term bladder voiding dysfunction.

Correlation of cardiac autonomic functions with uroflowmetry parameters in Type 2 diabetes mellitus patients – Analytical cross-sectional study

Background: Diabetic autonomic neuropathy can affect the autonomic nervous system (ANS) as a whole and result in a detrimental impact on cardiovascular, gastrointestinal, and genitourinary systems. However, urinary bladder dysfunction is one of the most important complications of long-standing and poorly controlled diabetes mellitus (DM) and often impairs the quality of life presenting as an under-recognized complication of diabetes. Cardiac autonomic functions are also severely affected in DM, leading to cardiovascular autonomic neuropathy (CAN). Hence, the present study aimed at correlating the urinary bladder functions with cardiac autonomic functions in Type 2 diabetic patients. Aims and Objectives: The aim of the study was to assess the cardiac autonomic functions using a cardiac ANS study (CANS study) and correlate it with the urinary bladder functions using uroflowmetry studies in Type 2 DM patients. Materials and Methods: This is an analytical cross-sectional study, with a sample size of 31 Type 2 DM patients recruited from the diabetology ward of Rajiv Gandhi Government General Hospital, Madras Medical College, Chennai. The patients were clinically examined and the history was collected. The Uroflowmetry test was done in the Department of Urology and the CANS study was done in the Department of Diabetology and the parameters were recorded in Microsoft Excel and analyzed using Statistical Package for the Social Sciences software. Results: A majority of subjects had significant severe and definite sympathetic involvement and early and definite cardiac autonomic neuropathy in the CANS study. Subjects with cardiac autonomic neuropathy had a negative correlation with voided volume, maximum flow rate, and average flow rate and a positive correlation with voiding time, and post-voided residual urine volume. Conclusion: According to this study, subjects with uncontrolled diabetes had predominant sympathetic nervous system dysfunction and also early, definite cardiac autonomic neuropathy. Subjects with early cardiac autonomic neuropathy had significant alterations in the uroflowmetry parameters indicating bladder voiding dysfunction in them. Hence, CANS study and uroflowmetry can be used to determine early ANS dysfunction in DM.

Th1/17 polarization and potential treatment by an anti-interferon-γ DNA aptamer in Hunner-type interstitial cystitis

Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette-Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17+polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a mouse anti-IFN-γ DNA aptamer and observed that the intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed murine HIC model with little migration into the blood. Our study provides the plausible basis for the clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.

Heparanase 2 (Hpa2)- a new player essential for pancreatic acinar cell differentiation

Heparanase 2 (Hpa2, HPSE2) is a close homolog of heparanase. Hpa2, however, lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase enzymatic activity. Mutations of HPSE2 were identified in patients diagnosed with urofacial syndrome (UFS), a rare genetic disorder that exhibits abnormal facial expression and bladder voiding dysfunction, leading to renal damage and eventually renal failure. In order to reveal the role of HPSE2 in tissue homeostasis, we established a conditional Hpa2-KO mouse. Interestingly, the lack of Hpa2 was associated with a marked decrease in the expression of key pancreatic transcription factors such as PTF1, GATA6, and Mist1. This was associated with a two-fold decrease in pancreas weight, increased pancreatic inflammation, and profound morphological alterations of the pancreas. These include massive accumulation of fat cells, possibly a result of acinar-to-adipocyte transdifferentiation (AAT), as well as acinar-to-ductal metaplasia (ADM), both considered to be pro-tumorigenic. Furthermore, exposing Hpa2-KO but not wild-type mice to a carcinogen (AOM) and pancreatic inflammation (cerulein) resulted in the formation of pancreatic intraepithelial neoplasia (PanIN), lesions that are considered to be precursors of invasive ductal adenocarcinoma of the pancreas (PDAC). These results strongly support the notion that Hpa2 functions as a tumor suppressor. Moreover, Hpa2 is shown here for the first time to play a critical role in the exocrine aspect of the pancreas.

HF02-10 AT THE EPICENTER OF INNOVATION IN THE 1970S: DR. JACK LAPIDES' RIGHT-HAND MAN, DR. ANANIAS DIOKNO

You have accessJournal of UrologyCME1 Apr 2023HF02-10 AT THE EPICENTER OF INNOVATION IN THE 1970S: DR. JACK LAPIDES' RIGHT-HAND MAN, DR. ANANIAS DIOKNO Justin Refugia and Gopal Badlani Justin RefugiaJustin Refugia More articles by this author and Gopal BadlaniGopal Badlani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003242.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Dr. Jack Lapides’ research in urology is widely recognized. His mentee, Dr. Ananias Diokno, was paramount to this work. We present Dr. Diokno’s contributions to highlight his role in pioneering treatments in neuro-urology and review a portion of his innumerable accomplishments. METHODS: We reviewed literature published by Drs. Lapides and Diokno to define their collaborative efforts. Web searches were performed with Google Scholar and PubMed and internal searches of our institution’s libraries. RESULTS: Dr. Lapides’ fruitful career largely occurred at the University of Michigan (UM). During his residency under the direction of Dr. Nesbit, his academic prowess was honed. In the 1960s, he became known for sentinel works on bladder physiology and voiding dysfunction. An important young person looking up to him was Dr. Diokno, a recent graduate of the University of Santo Tomas in the Philippines. In the late 1960s, Dr. Lapides went on to mentor him, later recruiting him to the UM urology residency and then Babcock Fellowship. One influential contribution that Dr. Diokno assisted with was the controversial study of non-sterile, clean intermittent catheterization (CIC) that challenged Dr. Guttman’s sterile approach. The team successfully taught CIC to patients with voiding dysfunction to prevent increased intravesical pressures. This lead to better control of their urinary difficulties and minimized UTIs, with no additional risks. Co-residents Drs. Diokno and Silber were astonished by the results. Initially, their enthusiasm was not met with a warm reception, yet the team persisted and saw their work revolutionize medicine worldwide. With his academic vigor, Dr. Diokno continued to move the needle during fellowship by discovering new categories of detrusor sphincter dyssynergia (DSD) and went on to establish use of CIC in clinical practice. CONCLUSIONS: Beyond the 1970s, Dr. Diokno maintained a remarkable career. He pioneered the initial efforts of geriatric incontinence by leading the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) efforts on community dwelling elderly as a separate category than institutionalized elderly. He also led the Beaumont Health System to becoming a recognized center for voiding dysfunction, first as the chair of urology and later as the chief medical officer (CMO). Many American and Asian urologists have benefitted from Dr. Diokno’s contributions and for this he deserves continued recognition. Source of Funding: N/a © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e253 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin Refugia More articles by this author Gopal Badlani More articles by this author Expand All Advertisement PDF downloadLoading ...

Effect of the neuropathic pain receptor P2X3 on bladder function induced by intraperitoneal injection of cyclophosphamide (CYP) in interstitial cystitis rats.

BackgroundThe role of purinergic receptor P2X3 in pathological bladder dysfunction and chronic pelvic pain remains unclear. We aim to investigate the effect of P2X3 on bladder function in interstitial cystitis (IC) through the IC rat model induced by cyclophosphamide (CYP).MethodsA total of 120 female Sprague-Dawley (SD) rats were randomly divided into 6 groups: control, CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups. The control group was injected with normal saline. The rats in the CYP-4h and CYP-48h groups were given a single high dose. The rats in the CYP-10d, CYP-30d, and CYP-45d groups were given a low dose of CYP repeatedly every three days. Bladder voiding function was measured using urodynamic techniques to observe the effect of the P2X3 receptor on bladder function in CYP-induced IC.ResultsThe rats in the CYP-4h group showed significant overactivity of the bladder compared with the control group, the bladder voiding interval was shortened (P<0.01), and the maximal voiding pressure was increased (P<0.01). At the same time, the degree of overactive bladder in the CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups became increasingly serious, the interval of bladder micturition was shortened stepwise (P<0.01), and the maximal micturition pressure was increased stepwise (P<0.01). Compared with the control group, the CYP-48h group mainly showed a shorter bladder voiding interval (P<0.01), lower voiding volume, and higher activation of mast cells and inflammatory factors in the bladder. In the CYP-10d group, bladder mast cell activation and inflammatory factors increased significantly. Intrathecal injection (IT) of A-317491 significantly prolonged the bladder voiding intervals in CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d rats (P<0.01), and the maximal voiding pressure of the CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups was significantly decreased (P<0.05), while the maximal voiding pressure of the CYP-10d group was not significantly affected.ConclusionsP2X3 receptors in dorsal root ganglion (DRG) play an important role in bladder function induced by intraperitoneal injection of CYP in rats. IT of P2X3 inhibitors can significantly improve the grade of bladder voiding dysfunction and chronic pelvic pain.

Urinary Symptoms and Bladder Voiding Dysfunction Are Common in Young Men with Defecatory Disorders: A Retrospective Evaluation.

Lower urinary tract symptoms (LUTS) are frequently reported by constipated patients. Prospective studies investigating the association between defecatory disorders (DDs) and voiding dysfunction, predominantly in women, have reported conflicting results. This study investigated (1) the prevalence of LUTS in young men with DDs and (2) the association between objectively documented DDs and voiding dysfunction in constipated young men with LUTS. We reviewed the medical records, including validated questionnaires, of men aged 18-40 with confirmed DDs treated with pelvic floor physical therapy (PT) at our institution from May 2018 to November 2020. In a separate group of constipated young men with LUTS who underwent high-resolution anorectal manometry (HRM), rectal balloon expulsion test (BET), and uroflowmetry, we explored the relationship between DDs and voiding dysfunction. A total of 72 men were evaluated in the study. Among 43 men receiving PT for a proven DD, 82% reported ≥ 1 LUTS, most commonly frequent urination. Over half of these men experienced a reduction in LUTS severity after bowel-directed pelvic floor PT. Among 29 constipated men with LUTS who had undergone HRM/BET and uroflowmetry, 28% had concurrent defecatory and voiding dysfunction, 10% had DD alone, 14% had only voiding dysfunction, and 48% had neither. The presence of DD was associated with significantly increased odds of concurrent voiding dysfunction (odds ratio 9.3 [95% CI 1.7-52.7]). Most young men with DDs experience LUTS, which may respond to bowel-directed physical therapy. Patients with DD and urinary symptoms have increased odds of voiding dysfunction.

Molecular mechanisms of voiding dysfunction in a novel mouse model of acute urinary retention.

Acute urinary retention (AUR) is a common urological emergency and affects a significant patient population. The inability to eliminate urine may lead to permanent damage to the bladder's structure and functioning. However, we know little about the underlying molecular sequelae to the urine retention. To closely mirror the potential high pressures that patients with AUR could experience, we catheterized anesthetized female mice via the urethra and filled the bladder by pumping saline (25 µL/min) into the bladder lumen to 50 cm or 80 cm water pressure. A water column with designated height (50 or 80 cm) was then adjusted to maintain constant pressure in the bladder lumen for 30 minutes. Functional and morphological evaluations were performed from 0 to 24 hours after AUR treatment. Mice exhibited incontinence and overactivity with diminished voiding pressure. Significant injury was confirmed which revealed bladders with disrupted urothelial barrier, edematous lamina propria, and distorted muscle bundles. Bladder smooth muscle (BSM) from pressure-treated mice have significantly diminished contraction force, suggesting that bladder voiding dysfunction can be attributed to impaired BSM contractility. Indeed, dysregulation of acetylcholine and purinergic signaling pathways were demonstrated, indicating that reduced efficacy of these pathways contributes to impaired BSM contractility. Finally, altered expression of β1-integrin and extracellular matrix mediated mechanotransduction pathways were detected, suggesting a profound remodeling process. These data demonstrated an easy to perform, quantifiable, and reproducible AUR mouse model, which mimics well the characteristics of human AUR patients, and our data generate new insights into the molecular mechanisms that occur following AUR.

Dual diagnosis of Ochoa syndrome and Niemann-Pick disease type B in a consanguineous family

Ochoa syndrome (UFS1; Urofacial syndrome-1) is a very rare autosomal recessive disorder caused by mutations in the HPSE2 gene that results bladder voiding dysfunction and somatic motor neuropathy affecting the VIIth cranial nerve. Niemann-Pick disease is a rare autosomal recessive lysosomal storage disorder with systemic involvement resulting from sphingomyelinase deficiency and generally occurs via mutation in the sphingomyelin phosphodiesterase-1 gene (SMPD1). Here, we report a 6-year-old girl with symptoms such as urinary incontinence, recurrent urinary tract infections, peculiar facial expression, mainly when smiling, hypertelorism, constipation, incomplete closure of eyelids during sleep and splenomegaly. Homozygote mutations in two different genes responsible for two distinct syndromes were detected in the patient. Homozygous NM_000543.5:c.502G>A (p.Gly168Arg) mutation was found in the SMPD1 gene causing Niemann-Pick disease. In addition, some of the clinical features were due to a novel homozygous mutation identified in the HPSE2 gene, NM_021828.5:c.755delA (p.Lys252SerfsTer23). Here, we discuss about the importance of considering dual diagnosis in societies where consanguineous marriages are common. Accurate diagnosis of the patient is very important for the management of the diseases and prevention of complications.

Combined vaginal-laparoscopic approach vs. laparoscopy alone for prevention of bladder voiding dysfunction after removal of large rectovaginal endometriosis.

To assess whether the combined vaginal-laparoscopic route may reduce the risk of postoperative bladder atony, when compared to an exclusively laparoscopic approach, in patients presenting with deeply infiltrating rectovaginal endometriosis with extensive vaginal infiltration. Retrospective comparative cohort study using data prospectively recorded in the CIRENDO database. Academic Tertiary Care Centre. One hundred and thirty-two consecutive patients who underwent surgery of rectovaginal endometriosis with vaginal infiltration measuring greater than 3cm diameter. Combined vaginal-laparoscopic versus laparoscopic approach. Sixty-two patients underwent excision of endometriosis via a combined vaginal-laparoscopic approach (study group, or cases), while 71 patients underwent surgery via an exclusively laparoscopic route (controls). Rates of preoperative cyclical voiding difficulty and sensation of incomplete bladder emptying were comparable between the two groups. Preoperative urodynamic assessment was carried out in 18% of cases and 38% of controls, with abnormal results in 27.3% and 11.1% of cases and controls respectively. Early postoperative voiding difficulty (post-void residual>100mL) occurred in 14.7% and 24.3% of cases and controls respectively. There was a significant reduction in risk of intermittent self-catheterisation of 13% at time of discharge in the study cases. Three months postoperatively, one case and 6 controls had persistent voiding dysfunction requiring prolonged self-catheterisation. The combined vaginal-laparoscopic approach for large rectovaginal endometriotic nodules could reduce the risk of postoperative bladder dysfunction, when compared to an exclusively laparoscopic approach, most likely due to a reduced risk of damage to the pelvic splanchnic nerves at the paravaginal level.

Surgery-related complications and long-term functional morbidity after segmental colo-rectal resection for deep infiltrating endometriosis (ENDO-RESECT morb).

Segmental resection has been generally associated with increased peri-operative risk of major complications. While major complications are widely acknowledged, minor complications, such as slight, to moderate infections, peripheral sensory disturbances, bladder voiding dysfunction, postoperative urinary obstruction, and sexual disorders are less reported. The aim of this study is to investigate the surgery-related complications and functional disorders, as well as to evaluate their persistence after long-term follow-up in women undergone segmental resection for deep infiltrating endometriosis. Special attention is given to evaluating impairments of bowel, bladder, and sexual function. All clinical data obtained from medical records of women who underwent segmental resection for intestinal endometriosis between October 2005, and November 2017, in Catholic University Institutions. Perioperative morbidity was classified by Extended Clavien-Dindo classification. Postoperative intestinal, voiding, and sexual morbidity was estimated by the compilation of specific questionnaires. Fifty women were included in the study. Forty-three high colorectal resections (86%), 6 low resections (12%), and 1 ultra-low resection (2%) were performed, while in 3 cases (6%) multiple resections were needed. The overall complication rate was 44%. Nineteen women (38%) experienced early complications and 3 women (6%) late complications. Long-term functional postoperative complications were composed of intestinal in 30%, urinary in 50%, and sexual in 64% of the study population. Median follow-up was 55.5months. Segmental resection, when indicated, offers a radical and feasible approach for bowel deep infiltrating endometriosis, resulting in an improved general quality of life. The bowel and bladder complications appear to be acceptable and often reversible. Postoperative sexual dysfunctions, such as anorgasmia and insufficient vaginal lubrication, appear to persist over time. Surgeons and women have to be aware of the incidence of this kind of complications.

Les cystostomies continentes – indications et principes de prise en charge

To specifically introduce continent cystostomy -indications, surgical technique, complications and management- to the nurses working in a urology department. The present article is based on a review of the literature and author's experience in continent cystostomy. Continent cystostomy is a neo-conduit placed between the bladder and the anterior abdominal wall using the digestive tract. It is usually performed in patients with bladder voiding dysfunction who cannot undergo clean self-intermittent catheterization through the urethra. The high success rate (>84%) associated with this procedure should not hide the frequent associated complications with the conduit. Even if continent cystostomy is associated with good mid- and long-term functional outcomes, it requires a close follow-up and in some cases "adjustments".

Cystitis-induced bladder pain is Toll-like receptor 4 dependent in a transgenic autoimmune cystitis murine model: a MAPP Research Network animal study.

Altered Toll-like receptor (TLR)4 activation has been identified in several chronic pain conditions but has not been well studied in interstitial cystitis/bladder pain syndrome (IC/BPS). Our previously published human studies indicated that patients with IC/BPS present altered systemic TLR4-mediated inflammatory responses, which were significantly correlated with reported pain severity. In the present study, we sought to determine whether altered TLR4 activation plays a role in pelvic/bladder pain seen in patients with IC/BPS using our validated IC/BPS-like transgenic autoimmune cystitis model (URO-OVA). URO-OVA mice developed responses consistent with pelvic and bladder pain after cystitis induction, which was associated with increased splenocyte production of TLR4-mediated proinflammatory cytokines IL-1β, IL-6, and TNF-α. Increased spinal expression of mRNAs for proinflammatory cytokines IL-6 and TNF-α, glial activation markers CD11b and glial fibrillary acidic protein, and endogenous TLR4 ligand high mobility group box 1 was also observed after cystitis induction. Compared with URO-OVA mice, TLR4-deficient URO-OVA mice developed significantly reduced nociceptive responses, although similar bladder inflammation and voiding dysfunction, after cystitis induction. Intravenous administration of TAK-242 (a TLR4-selective antagonist) significantly attenuated nociceptive responses in cystitis-induced URO-OVA mice, which was associated with reduced splenocyte production of TLR4-mediated IL-1β, IL-6, and TNF-α as well as reduced spinal expression of mRNAs for IL-6, TNF-α, CD11b, glial fibrillary acidic protein, and high mobility group box 1. Our results indicate that altered TLR4 activation plays a critical role in bladder nociception independent of inflammation and voiding dysfunction in the URO-OVA model, providing a potential mechanistic insight and therapeutic target for IC/BPS pain.

Chronic linaclotide treatment reduces colitis-induced neuroplasticity and reverses persistent bladder dysfunction.

Irritable bowel syndrome (IBS) patients suffer from chronic abdominal pain and extraintestinal comorbidities, including overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC-PBS). Mechanistic understanding of the cause and time course of these comorbid symptoms is lacking, as are clinical treatments. Here, we report that colitis triggers hypersensitivity of colonic afferents, neuroplasticity of spinal cord circuits, and chronic abdominal pain, which persists after inflammation. Subsequently, and in the absence of bladder pathology, colonic hypersensitivity induces persistent hypersensitivity of bladder afferent pathways, resulting in bladder-voiding dysfunction, indicative of OAB/IC-PBS. Daily administration of linaclotide, a guanylate cyclase-C (GC-C) agonist that is restricted to and acts within the gastrointestinal tract, reverses colonic afferent hypersensitivity, reverses neuroplasticity-induced alterations in spinal circuitry, and alleviates chronic abdominal pain in mice. Intriguingly, daily linaclotide administration also reverses persistent bladder afferent hypersensitivity to mechanical and chemical stimuli and restores normal bladder voiding. Linaclotide itself does not inhibit bladder afferents, rather normalization of bladder function by daily linaclotide treatment occurs via indirect inhibition of bladder afferents via reduced nociceptive signaling from the colon. These data support the concepts that cross-organ sensitization underlies the development and maintenance of visceral comorbidities, while pharmaceutical treatments that inhibit colonic afferents may also improve urological symptoms through common sensory pathways.

Bladder augmentation in children: current problems and experimental strategies for reconstruction.

SummaryBladder augmentation is a demanding surgical procedure and exclusively offered for selected children and has only a small spectrum of indications. Paediatric bladder voiding dysfunction occurs either on a basis of neurological dysfunction caused by congenital neural tube defects or on a basis of rare congenital anatomic malformations. Neurogenic bladder dysfunction often responds well to a combination of specific drugs and/or intermittent self-catheterization. However, selected patients with spinal dysraphism and children with congenital malformations like bladder exstrophy and resulting small bladder capacity might require bladder augmentation. Ileocystoplasty is the preferred method of bladder augmentation to date. Because of the substantial long-and short-term morbidity of augmentation cystoplasty, recent studies have tried to incorporate new techniques and technologies, such as the use of biomaterials to overcome or reduce the adverse effects. In this regard, homografts and allografts have been implemented in bladder augmentation with varying results, but recent studies have shown promising data in terms of proliferation of urothelium and muscle cells by using biological silk grafts.

Effects of electroacupuncture on bladder and bowel function in patients with transverse myelitis: a prospective observational study.

ObjectiveTo preliminarily explore the effect of electroacupuncture (EA) on bladder and bowel dysfunction in patients with transverse myelitis.MethodsSixteen participants were treated with EA at bilateral BL32, BL33, and BL35 once a day, five times a week for the first 4 weeks, and once every other day, three times a week for the following 4 weeks. Patients were then followed up for 6 months. Bladder and bowel function, and the safety of EA, were assessed.ResultsAfter 8 weeks of treatment, five (5/16, 31%) patients resumed normal voiding, three (6/16, 38%) regained partially normal voiding, and five (5/16, 31%) had no change. After treatment, the residual urine volume decreased by 100 mL (IQR 53–393 mL; P<0.05) in nine patients with bladder voiding dysfunction; in 11 patients with urinary incontinence, the number of weekly urinary incontinence episodes, 24-hour urinary episodes, and nocturia episodes per night diminished by 14 (95% CI 5 to 22), 5 (95% CI 1 to 9), and 4 (95% CI 0 to 7) episodes, respectively (all P<0.05). After 8 weeks of treatment in eight patients with faecal retention, four (4/8, 50%) resumed normal bowel movements, three (3/8, 38%) regained partially normal bowel movements, and one (1/8, 13%) had no change.ConclusionsEA might be a promising alternative for the management of bladder and bowel dysfunction in patients with transverse myelitis. Randomised controlled trials are needed to confirm the effectiveness and safety of EA for this condition.

Durasphere® EXP: a non-biodegradable agent for treatment of primary Vesico-Ureteral reflux in children

ABSTRACTIntroduction:Durasphere® EXP (DEXP) is a compound of biocompatible and non--biodegradable particles of zirconium oxide covered with pyrolytic carbon. The aim of this study is to evaluate the durability of off-label use of DEXP in the treatment of primary vesicoureteral reflux in children.Materials and Methods:Patients who underwent subureteric injection of DEXP for the correction of primary VUR were retrospectively reviewed. Patients aged >18 years as well as those who had grade-I or -V VUR, anatomic abnormalities (duplicated system, hutch diverticulum), neurogenic bladder or treatment refractory voiding dysfunction were excluded. Radiologic success was defined as the resolution of VUR at the 3rd month control. Success was radiographically evaluated at the end of the first year.Results:Thirty-eight patients (9 boys, 29 girls; mean age, 6.3±2.7 years) formed the study cohort. Forty-six renal units received DEXP (grade II: 22; grade III: 18; grade IV: 6). Mean volume per ureteric orifice to obtain the mound was 0.70±0.16mL. First con- trol VCUG was done after 3 months in all patients. After the first VCUG, 6 patients had VUR recurrence. Short-term radiologic success of DEXP was 84.2%. Rate of radiologic success at the end of the first year was 69.4% (25/32). Lower age (p:0.006) and lower amount of injected material (p:0.05) were associated with higher success rates at the end of 1 year.Conclusion:This is the first study to assess the outcomes of DEXP for treatment of primary VUR in children. After 1 year of follow-up, DEXP had a 69.4% success rate.

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats.

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Transcystometrograms were performed in urethane-anesthetized rats. The in vitro and in vivo reactive oxygen species levels and pathological changes in formalin-fixed bladder sections were evaluated. Western blotting and immunohistochemistry elucidated the pathophysiological mechanisms of oxidative stress-induced apoptosis, autophagy, and pyroptosis. P-phenylenediamine increased voiding frequency, blood and urinary bladder levels of reactive oxygen species, and neutrophil and mast cell infiltration. It also upregulated biomarkers of autophagy (LC3 II), apoptosis (poly (ADP-ribose) polymerase), and pyroptosis (Caspase 1). WCT003 and WCT006 ameliorated reactive oxygen species production, inflammation, apoptosis, autophagy, pyroptosis, and bladder hyperactivity. P-phenylenediamine increased oxidative stress, inflammatory leukocytosis, autophagy, apoptosis, and pyroptosis formation within the urinary bladder. Novel synthetic nickel-containing superoxide dismutase mimics relieved p-phenylenediamine-induced bladder inflammation and voiding dysfunction.

Resveratrol improves urinary dysfunction in rats with chronic prostatitis and suppresses the activity of the stem cell factor/c-Kit signaling pathway.

Chronic prostatitis (CP) is a common urological disorder, with bladder voiding dysfunction being the primary clinical manifestation. Resveratrol is polyphenolic compound isolated from numerous plants, with widely‑reported anti-inflammatory properties. The present study aimed to investigate whether resveratrol may improve overactive bladder in rats with CP and to investigate the underlying molecular mechanisms. Furthermore, the potential pharmacological synergy between resveratrol and solifenacin was also investigated as a potential treatment for CP. Following the successful establishment of a rat model of CP by subcutaneously injecting DPT vaccine, rats were treated with resveratrol or a combination of resveratrol+solifenacin. Bladder pressure and volume tests were performed to investigate the effect of resveratrol and solifenacin on urinary dysfunction in rats with chronic prostatitis. Western blot analysis and immunohistochemical staining were used to examine the expression of c‑Kit receptor, stem cell factor (SCF), AKT and phosphorylated‑AKT (p‑AKT) in the bladder tissue. The results of the bladder pressure and volume test indicated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure in the control group were 0.57ml, 0.17ml and 29.62cmH2O, respectively. These values were increased by 71, 27 and 206% in rats in the CP group compared with the control group. Following treatment with resveratrol, the results in the resveratrol group were reduced by 25.77, 44.23 and 13.32% compared with the CP group. The results of western blot analysis, immunohistochemical staining and immunofluorescence labeling demonstrate that the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats in the CP group was 4.32, 6.13 and 6.31times higher compared with the control group, respectively. Following treatment with resveratrol, protein expression was significantly reduced. However, no significant differences were observed between the protein expression of the SCF, c‑Kit and p‑AKT in the bladder between the resveratrol and combination groups. In conclusion, resveratrol may improve overactive bladder by downregulating the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats with CP. Furthermore, a combination of resveratrol and solifenacin may have potential pharmacological synergy as a treatment for patients with CP.