Urothelial Inflammation Research Articles

β-Adrenoceptors regulate urothelial inflammation and zonula occludens in the bladder outlet obstruction model

BackgroundThe purpose of this study was to evaluate the effects of β-adrenoceptors (ADRBs) on the urothelial inflammation and zonula occludens (ZO) in a rat PBOO model and in an in vitro model. MethodsThe PBOO model was established by ligating the bladder neck of rats. Twenty rats were divided into 4 groups: sham operation, PBOO + normal saline, PBOO + ADRB2 agonist, PBOO + ADRB3 agonist. PBOO rats were with treated with ADRBs agonists for 3 weeks. Human urothelial cells (HUCs) were subjected to ADRBs agonist treatment or hydrostatic pressure in an in vitro model. ResultsIn the PBOO group, there was a significant increase in the expression of MCP-1, IL-6 and RANTES compared to the sham group. By contrast, there was a post-PBOO decline in the expression of ZO-1 and ZO-2 in the urothelium. ADRB2 or ADRB3 agonists exhibited downregulated inflammatory cytokine expression and increased ZO expression in the PBOO model. The regulation of inflammation and ZO by ADRB2 and ADRB3 agonists in an in vitro model was found consistent with that in the PBOO model. Moreover, RhoA and ROCK inhibitors suppressed the expression of hydrostatic pressure-induced inflammatory cytokines. Additionally, RhoA agonist reversed the inhibitory effect of ADRBs agonists on the inflammatory secretion from HUCs. ConclusionsADRB2 and ADRB3 agonists increased ZO protein expression in HUCs in a rat PBOO model and in an in vitro model. Furthermore, ADRB2 and ADRB3 agonists inhibited the secretion of inflammatory cytokines from HUCs by regulating the RhoA/ROCK signaling pathways.

Micronized Palmitoylethanolamide, Hempseed Oil, and Maritime Pine Bark Dry Extract (Pelvipea®) for Pelvic Pain: An In Vitro Study for Urothelial Inflammation Treatment.

Urothelial inflammation plays a key role in the pathogenesis of chronic pelvic pain due to its origin in the bladder. The aim of this study was to evaluate the efficacy of a patent-pending formulation (Pelvipea®) composed of micronized palmitoylethanolamide (PEA), hempseed oil, and maritime pine bark dry extract in reducing urothelial inflammation, as well as the effect of each ingredient individually, in order to define the synergistic effect of the three ingredients. An in vitro bladder urothelium model composed of the T24 cell line was exposed to a conditioned media obtained by treating macrophage-differentiated THP-1 cells with different concentrations of the functional ingredients and a mixture of them in the presence of the pro-inflammatory stimulus of Escherichia coli. Cells exposed only to the inflammatory stimulus in the absence of pre-treatment were considered as a positive control for inflammation. The impact of each functional ingredient and their mixture on inflammation was evaluated by the determination of transcription factor NF-kB and of pro-inflammatory cytokine expression. Statistical analysis was performed using the t-test, comparing the mixture and the single ingredients for every condition tested. All results were reported as fold change (mean ± standard deviation), the ratio between the values obtained from the respective treatments for inflammation control. The three functional ingredients did not induce negative effects on THP-1 cell vitality. The levels of NF-kB were reduced following treatment with hempseed oil, maritime pine bark dry extract, and the mixture at all tested concentrations, and with micronized PEA from 25 to 200 μg/mL. Treatment with the mixture resulted in the lowest expression levels of interleukins (IL)-1β, IL-6, and IL-8 compared to the single functional ingredients at a concentration of 230 μg/mL, with values of 0.08 (±0.00), 0.01 (±0.00), and 0.32 (±0.01), respectively. The mixture of micronized PEA, hempseed oil, and maritime pine bark dry extract (Pelvipea®) at 230 μg/mL showed the best efficacy in urothelial IL-1β, IL-6, and IL-8 reduction compared with the singular components. This formulation may represent a promising therapeutic option to relieve painful symptoms originating in the bladder. However, in vivo studies are needed to confirm these results.

Patterns of mutations in nine cancer-related genes and PAF development among smoking male patients diagnosed with bladder cancer.

Smoking is one of the most popular risk factors provoking bladder cancer (BC). This research intended to estimate cigarette smoking effect involving PAF signs between smoking patients with BC and non-smoking patients with same diagnosis to define relations with pathological characteristics and their prognosis on zero-relapse and disease-associated recovery. Two groups of smokers (n = 54) and non-smokers (n = 62) were selected. Both cohorts of patients had BC. They were evaluated utilizing NGS on 9 cancer-related genes and confirmed through the Sanger DNA sequencing and histopathological tests based on H&E staining. The factor of smoking and impact of PAF development by ELISA assay and PAF-R manifestation in terms of immunochemical evaluation on BC areas comparing to a control group (n = 30) was examined involving healthy contributors, including the use of well-designed statistical trials. The multivariate evaluation showed considerable rise in mutation patterns related to smoking among BC patients (group 3), increase in PAF development (***P<0.001) and vivid signs of PAF-R contrasted to non-smokers with BC (group 2) and control group (group 1). All the identified biological changes (gains/losses) were recorded at the same locations in both groups. Patients from group 3 held 3-4 various mutations, while patients from group 2 held 1-3 various mutations. Mutations were not identified in 30 respondents from control group. The most repeated mutations were identified in 3 of 9 examined genes, namely TP53, PIK3CA and PTEN, with highest rates of increase in Group 3. Moreover, histopathological tests revealed barely identifiable and abnormal traits in BC tissues, i.e. were without essential histopathological changes between groups 2 and 3. Smoking of cigarettes provokes PAF development due to urothelial inflammation and rise of mutations in 9 cancer-related genes. These are indicative factors of inducing BC.

Increased Chronic Urothelial Inflammation and its Association with Urinary Tract Infection

Introduction: Inflammation of the bladder can be due to both noninfectious and infectious etiologies. The most common cause of infectious cystitis has been Escherichia coli. Objectives: The basic aim of the study is to find the increased chronic urothelial inflammation and its association with urinary tract infection. Material and methods: This cross sectional study was conducted in Ganga Ram hospital, Lahore during June 2020 to December 2020. The data was collected from 50 patients. Bladder symptoms and lower urinary tract conditions were investigated. All patients were treated actively according to the latest urine culture and followed by antimicrobial prophylaxis for at least 1 month. Results: The data was collected from 50 patients. The mean age was 45± 3.56 years for male and 52.3 ± 8.89 years for females. The analysis of data shows the differences in urodynamic variables between the control subjects and the ESRD/CKD patients. Conclusion: It is concluded from our study that increased urothelial inflammation and apoptosis and decreased cell expression were found in patients with ESRD/CKD.

Clinicopathological Analysis of Chronic Urothelial Inflammation Associated with UTI in Women

Introduction: Urinary tract infection (UTI) is a typical grumbling experienced in outpatient setting, regardless of whether essential care or expert facility. Objectives of the study: The basic aim of the study is to analyses the clinicopathological analysis of chronic urothelial inflammation associated with UTI in women. Material and methods: This cross sectional study was conducted in Foundation University Medical College Islamabad During March 2021 till November 2021. The data was collected through non-probability consecutive sampling technique. Results: The data was gathered from 100 patients. The examination of data shows the distinctions in urodynamic factors between the control subjects and the ESRD/CKD patients. In general, the ESRD/CKD patients had fundamentally lower FS, US, and CBC than did the controls. Patients with ESRD/CKD with DU had altogether lower FS, CBC in ESRD/DU patients with BO (table 01). Conclusion: It is concluded from our study that chronic inflammation, urothelial cell apoptosis and impairment of barrier function of urothelial cells could be the underlying pathophysiology of recurrent UTI in women. Keywords: UTI, Women, Pathology, Urothelial

Pathological and Clinicopathological Features of Canine and Feline Bladder Disease

Dogs and cats commonly present to veterinary hospitals with urinary bladder disease, but despite their clinical importance and comparative potential to human diseases, bladder diseases in Australian dogs and cats are under investigated. In veterinary pathology, insufficient levels of diagnostic agreement can occur, and this is influenced by sample quality as well as the pathologist’s own experience, training, and cognitive biases. Logistic regression is a statistical technique which, when applied to veterinary histopathology, could improve pathologist agreement. Thus, there were two overarching goals of this thesis - to investigate the pathology and comparative potential of canine and feline urinary bladder disease in Australia, and to explore the utility of logistic regression modelling in improving inter-pathologist agreement.This project conducted a retrospective evaluation of pathology cases of canine and feline urinary bladder tissue from the veterinary pathology archives of the University of Queensland School of Veterinary Science and Murdoch University’s School of Veterinary and Life Sciences, with prospective sampling from veterinary clinics and a commercial veterinary pathology service in South East Queensland. The demographics of the dataset were examined using proportionate morbidity and logistic regression to identify associations between animal factors and the diagnosis. Secondly, a comprehensive histological evaluation was undertaken of every sample, with logistic regression modelling performed to identify associations between histological variables and diagnosis. Thirdly, a subset of canine and feline diseased and normal bladder tissue samples was tested for biomarker expression using immunohistochemistry and polymerase chain reaction. This combined approach tested if retrospective samples were of sufficient quality, and when validated provided quantity as well as cellular location of the target biomarkers. To further investigate the comparative potential of feline idiopathic cystitis (FIC), a systematic review was conducted on biomarkers in bladder pain syndrome (BPS) compared to FIC, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Finally, to investigate the role of logistic regression modelling in veterinary pathologist agreement, the modelling of histological variables was used to formulate a predictive probability tool which we then tested on four pathologists evaluating the same set of twenty-five slides, with diagnostic agreement evaluated using the Fleiss kappa statistic.The main findings from the demographic analysis were a higher risk of bladder neoplasia in dogs compared to cats, increasing risk for bladder neoplasia with age, and decreased risk for cystitis in neutered animals. Next, logistic regression modelling on the histology dataset of canine and feline urinary bladder tissue from Eastern and Western Australia identified six significant variables that3were associated with the diagnosis – urothelial ulceration, urothelial inflammation, neutrophilic submucosal inflammation, submucosal lymphoid aggregates, amount of submucosal haemorrhage, and species. These six variables were used to create a predictive probability tool for bladder disease diagnosis. The pathologist agreement study revealed a good level of agreement between the four pathologists when diagnosing neoplastic lesions, but poor to fair agreement for cystitis, urolithiasis and normal bladder tissue. Agreement between pathologists did improve when signalment and clinical history was provided, with mixed results on inter-pathologist agreement when the predictive probability tool was used. However, the predictive tool did prove valuable in increasing the agreement of the study pathologists’ diagnosis with the reference diagnosis. There were multiple other confounders at play in this experiment such as variable digital slide quality and different interpretations of the study instructions. A systematic review on biomarkers in bladder pain syndrome revealed that nerve growth factor is the most likely urine biomarker to be useful in the diagnosis of human BPS. The aim of this review had been to compare biomarkers in BPS to those in FIC, however an unexpected variability in the study parameters meant we could not fulfil this goal. A final laboratory-based investigation of biomarkers of canine and feline bladder diseases revealed two findings - that archived formalin fixed, paraffin embedded tissues are not good samples for PCR experiments, and secondly that tight junction protein-1 may be a promising tissue biomarker for differentiating between some urinary bladder diseases in dogs and cats.In conclusion, this thesis has undertaken a comprehensive analysis of the pathogenesis and comparative potential of canine and feline bladder diseases and is the first to apply logistic regression modelling to veterinary histopathology diagnosis and to improving inter-pathologist agreement. Logistic regression modelling is a promising tool for veterinary pathology. Dogs and cats are potentially good comparative models for human bladder diseases; however, inconsistent case definitions in human research complicates veterinary and medical field alignment. Finally, a collaborative multicentre approach would be invaluable to collect high quality prospective samples of feline idiopathic cystitis cases to allow further investigation into this disease. In summary, the comprehensive approach utilised in this thesis has provided valuable information on bladder disease in cats and dogs and sets a foundation for further work in this field.

Predicting Diagnosis of Australian Canine and Feline Urinary Bladder Disease Based on Histologic Features.

Anatomic pathology is a vital component of veterinary medicine but as a primarily subjective qualitative or semiquantitative discipline, it is at risk of cognitive biases. Logistic regression is a statistical technique used to explain relationships between data categories and outcomes and is increasingly being applied in medicine for predicting disease probability based on medical and patient variables. Our aims were to evaluate histologic features of canine and feline bladder diseases and explore the utility of logistic regression modeling in identifying associations in veterinary histopathology, then formulate a predictive disease model using urinary bladder as a pilot tissue. The histologic features of 267 canine and 71 feline bladder samples were evaluated, and a logistic regression model was developed to identify associations between the bladder disease diagnosed, and both patient and histologic variables. There were 102 cases of cystitis, 84 neoplasia, 42 urolithiasis and 63 normal bladders. Logistic regression modeling identified six variables that were significantly associated with disease outcome: species, urothelial ulceration, urothelial inflammation, submucosal lymphoid aggregates, neutrophilic submucosal inflammation, and moderate submucosal hemorrhage. This study demonstrated that logistic regression modeling could provide a more objective approach to veterinary histopathology and has opened the door toward predictive disease modeling based on histologic variables.

Risk factors for enterococcal bacteriuria in dogs: A retrospective study.

BackgroundIn humans, Enterococcus spp. urinary tract infections (UTI) are commonly associated with urinary catheter‐induced urothelial inflammation but this is not the case in dogs.Hypothesis/ObjectivesTo identify risk factors predisposing dogs to enterococcal bacteriuria.AnimalsSeventy dogs with Enterococcus spp. bacteriuria (case) and 70 dogs with Enterococcus coli bacteriuria (control).MethodsA single center retrospective case‐control study with subjects and controls identified by a medical records search for Enterococcus spp. (subject) or E coli (control) bacteriuria from January 1, 2014 to December 31, 2017. Cases and controls were balanced with respect to average age and weight. Binary logistic regression was used to estimate and test whether the odds of having Enterococcus spp. bacteriuria (instead of E coli) were associated with the presence of any given characteristic.ResultsA history of recurrent bacteriuria was significantly more common in Enterococcus spp. cases than in E coli controls (odds ratio [OR]: 2.07; 95% confidence interval [CI]: 1.04‐4.16, P = .04). Comorbidities associated with the presence of Enterococcus spp. bacteriuria included lower urinary tract (LUT) anatomic abnormalities (OR: 2.94; 95% CI: 1.17‐8.10, P = .02), urolithiasis (P = .01), and the presence of LUT neoplasia (P = .04). Small frequencies (n = 12 and n = 6, respectively) compromise our ability to precisely estimate the genuine OR for the latter 2 characteristics.Conclusions and Clinical ImportanceIf the identified risk factors promote Enterococcus spp. colonization in dogs via induced LUT inflammation similar to people then Enterococcus spp. bacteriuria could be a sentinel for underlying LUT inflammation.

The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A.

Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely “botulinum toxin A” (BoNT-A) and “overactive bladder”, with or without the additional keywords “detrusor overactivity”, “diabetes mellitus”, “inflammation”, and “urodynamic study”. We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy.

Adelmidrol + sodium hyaluronate in IC/BPS or conditions associated to chronic urothelial inflammation. A translational study

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, bladder inflammation and pain. It is a particular challenging disease and a clear unmet medical need in terms of identifying new therapeutic strategies. The aim of study was to evaluate the anti-inflammatory effects of intravesical Vessilen® (a new formulation of 2% adelmidrol (the diethanolamide derivative of azelaic acid) + 0.1% sodium hyaluronate) administration in rodent models of IC/BPS and in IC/BPS patients or other bladder disorders.Acute and chronic animal models of cystitis were induced by a single or repetitive intraperitoneal injections of cyclophosphamide (CYP); patients with IC/BPS or with bladder pain syndrome associated with symptoms of the lower urinary tract treated once weekly by bladder instillation of Vessilen® for 8 weeks.CYP instillation caused macroscopic and histological bladder alterations, inflammatory infiltrates, increased mast cell numbers, bladder pain, increased expression of nitrotyrosine, decreased expression of endothelial tight junction zonula occludens-1. Intravesical Vessilen® treatment was able to ameliorate CYP induced bladder inflammation and pain by inhibiting nuclear factor-κB pathway and inflammatory mediator levels as well as reduced mechanical allodynia and nerve growth factor levels. A significant improvement in quality of life and symptom intensity were evident in patients with IC/BPS or other bladder disorders treated with Vessilen®. Vessilen® could be a new therapeutic approach for human cystitis.

Urothelial dysfunction and sensory protein expressions in patients with urological or systemic diseases and hypersensitive bladder

ObjectiveTo investigate the underlying pathophysiology in the urothelium of different lower urinary tract diseases (LUTDs) and in patients with overactive bladder (OAB) or hypersensitive bladder (HSB), including chronic inflammation, barrier proteins, and sensory functional receptors. Materials and MethodsA total of 156 patients, including 14 with idiopathic OAB, 11 with detrusor overactivity and inadequate contractility (DHIC), 19 with end-stage renal disease (ESRD) and HSB, 26 with spinal cord injury (SCI) and detrusor overactivity (DO), 23 with bladder outlet obstruction (BOO) and DO, 19 with diabetes mellitus (DM) and OAB, 20 with interstitial cystitis (IC), and 24 with ketamine cystitis (KC) were investigated for urothelial dysfunction and sensory protein expressions. Twenty control patients without LUTD were invited and separated into two groups for comparative studies. All participants had urodynamically proven DO or increased bladder sensation on video urodynamic studies. Urothelial dysfunction and functional receptor expressions were investigated and compared between patients with LUTD and controls. ResultsAll patient subgroups had significant increases in mast cell activation and apoptotic cell counts and a decrease in E-cadherin expression. P2X3 expression was significantly decreased in DHIC but was increased in BOO/DO. Urothelial M3 expression was significantly increased in patients with OAB, BOO/DO, DM/OAB, and KC. M2 expression was significantly decreased in DHIC but increased in patients with BOO/DO. β3-AR expression was significantly decreased in patients with OAB and increased in patients with DHIC, ESRD/HSB, DM/OAB, and KC. Patients with OAB and BOO/DO had significantly increased M2/β3-AR. Lower M2/β3-AR was associated with lower voiding efficiency and large postvoid residual (PVR) in DHIC, ESRD/HSB, and SCI/neurogenic detrusor overactivity (NDO). ConclusionPatients with OAB or HSB showed increased urothelial inflammation and lower barrier protein expression. Increased M3/β3-AR or M2/β3-AR in the urothelium was associated with OAB, whereas decreased M3/β3-AR or M2/β3-AR was associated with poor voiding efficiency and large PVR in LUTD.

Clinical Efficacy and Changes of Urothelial Dysfunction after Repeated Detrusor Botulinum Toxin A Injections in Chronic Spinal Cord-Injured Bladder

Chornic spinal cord injury (SCI) will induce bladder urothelium dysfunction. This study investigated the therapeutic effects on urothelial dysfunction after repeated detrusor injections of onabotulinumtoxinA (BoNT-A) in SCI patients with neurogenic detrusor overactivity (NDO). Twenty chronic suprasacral SCI patients with NDO were enrolled. The patients received 300 U BoNT-A injection into the detrusor every six months. The urothelium was assessed by cystoscopic biopsy at baseline and six months after each BoNT-A treatment. Immunofluorescence staining for urothelial dysfunction, including E-cadherin, zonula occludens-1 (ZO-1), tryptase for mast cell activity, and urothelial apoptosis were investigated. The outcome of urothelial dysfunction parameters after BoNT-A injection were compared between baseline and six months after each treatment. Repeated 300 U BoNT-A injections showed a sustained decrease of detrusor pressure compared with baseline. After three repeated BoNT-A detrusor injections, significantly greater distributions of E-cadherin (p = 0.042) and ZO-1 (p = 0.003) expressions, but no significant changes, of urothelial apoptosis and mast cell activation were found after repeated BoNT-A therapy. Urothelial dysfunction, such as adhesive and junction protein concentrations in SCI patients’ bladders, recovered after three repeated cycles of BoNT-A treatment. The therapeutic effects sustained. However, urothelial inflammation and apoptosis after SCI were not significantly improved after three repeated BoNT-A injections.

Urothelial Dysfunction and Chronic Inflammation in Diabetic Patients with Overactive Bladder.

To investigate urothelial dysfunction, suburothelial inflammation, and muscarinic receptor expression in diabetic patients with overactive bladder (OAB). A total 19 patients with OAB and diabetes mellitus (DM), 14 OAB patients without DM, and 10 healthy control subjects were enrolled in the study. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase (mast cell activation), and apoptosis tests on the bladder urothelium and suburothelium were performed. Tissue muscarinic receptor M2, M3, and purinergic receptor P2X3 levels were measured by Western blotting. Video urodynamic studies were analyzed in relation to immunofluorescence and western blotting results. The mean age of the controls, OAB patients without and with DM were comparable (62.9 ± 6.9, 58.4 ± 21.3, and 68.9 ± 11.3 years, respectively, P = 0.25). E-cadherin and mast cell expression in the bladder urothelium samples of the DM-OAB group and the OAB group without DM differed significantly from those of the control group (all P < 0.05). However, immunofluorescence analyses including E-cadherin, mast cells, apoptotic cell counts, and ZO-1 were comparable between OAB patients with and without DM. In addition, M3 muscarinic protein expression in the bladders of OAB patients with and without DM was significantly higher than that in the control subjects. The video urodynamic parameters did not correlate with the immunofluorescence data, M2 and M3 muscarinic receptor data, or P2X3 protein expression. Urothelial dysfunction and chronic suburothelial inflammation may contribute to the pathogeneses of OAB. However, DM does not aggravate the severity of urothelial inflammation in OAB patients.

Urothelial dysfunction and chronic inflammation in patients with bladder outlet obstruction and different bladder dysfunction and different BOO degree

Urothelial dysfunction and chronic inflammation in patients with bladder outlet obstruction and different bladder dysfunction and different BOO degree

MP20-16 REDUCED BLADDER CAPACITY AND INCREASED BLADDER SENSATION IS ASSOCIATED WITH UROTHELIAL DYSFUNCTION AND CHRONIC INFLAMMATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND END-STAGE RENAL DISEASE

INTRODUCTION AND OBJECTIVES: Patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) may have reduced bladder capacity and compliance. Some patients also bother with severe frequency, urgency and frequent urinary tract infection (UTI). This study evaluated the urothelial dysfunction and chronic inflammation in the bladder mucosa from CKD or ESRD to clarify the pathophysiology of the bladder dysfunction in the bladder. METHODS: A total of 27 patients with CKD or ESRD with detrusor underactivity (DU) (n1⁄48), or with detrusor overactivity (DO) or hypersensitive bladder (HSB) (n1⁄419) were enrolled. Bladder mucosa specimens were obtained during transurethral procedures and were investigated for the adhesive protein E-cadherin, tight junction protein zonula occludens 1 (ZO-1), activated mast cell count by tryptase test, and urothelial apoptotic cell count by TUNEL. The urodynamic parameters were also evaluated and compared with a group of normal females without lower urinary tract symptoms. RESULTS: The bladder mucosa in CKD and ESRD showed significantly higher mast cell count and urothelial apoptosis and lower ZO-1 expression compared with the controls. E-cadherin was reduced in patients with ESRD/CKD with DU but not in ESRD/CKD with DO or HSB (Fig. 1). The expressions of ZO-1 and E-cadherin andmast cell activity were significantly associated with increased bladder sensation and small voided volume. Increased mast cell and apoptotic cell counts and decreased ZO-1 were more prominent in ESRD/CKD with DO or HSB (Table 1). CONCLUSIONS: Urothelial dysfunction and chronic inflammation are remarkable in the bladders of ESRD or CKD. Increased inflammation and defective barrier function are more prominent in ESRD/CKD bladder with DO of HSB. These urothelial pathophysiologies explain the bladder dysfunction and frequent UTI in the bladders of ESRD/CKD. Table 1 The urodynamic parameters and urothelial dysfunction in patients with chronic kidneydisease and end stage renal disease

MP31-05 UROTHELIAL DYSFUNCTION AND CHRONIC INFLAMMATION IN PATIENTS WITH BLADDER OUTLET OBSTRUCTION AND DIFFERENT BLADDER DYSFUNCTION AND DIFFERENT BLADDER OUTLET OBSTRUCTION DEGREE

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 2015MP31-05 UROTHELIAL DYSFUNCTION AND CHRONIC INFLAMMATION IN PATIENTS WITH BLADDER OUTLET OBSTRUCTION AND DIFFERENT BLADDER DYSFUNCTION AND DIFFERENT BLADDER OUTLET OBSTRUCTION DEGREE Chung-Cheng Wang, Jia-Hui Chang, and Hann-Chorng Kuo Chung-Cheng WangChung-Cheng Wang More articles by this author , Jia-Hui ChangJia-Hui Chang More articles by this author , and Hann-Chorng KuoHann-Chorng Kuo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1360AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The underlying mechanisms responsible for the bladder dysfunction in bladder outlet obstruction (BOO) remain poorly understood. The purpose of this study is to investigate the urothelial dysfunction and chronic inflammation in patients with BOO. METHODS In this prospective study, we enrolled those patients with LUTS. Based on their VUDS performances, it was categorized into 4 sub-groups: control, BOO with detrusor overactivity (DO), BOO with Detrusor underactivity (DU) and BOO with hypersenstivity bladder (HSB). Bladder tissues taken from these patients were analyzed. Immunofluorescence (IF) staining of junction protein E-cadherin, mast cell, TUNEL and zonula occludens 1(ZO-1) were performed. RESULTS A total of 44 men were enrolled in this study. There were 34 patients presented with BOO (DO: 12, DU: 11 and HSB: 11). The expression and cellular location of E-cadherin, mast cell, TUNEL and ZO-1 were illustrated in Fig. 1. The distribution of E-cadherin is significantly reduced in BOO with DU (8.37±9.50) (p<0.000), whereas exhibit highest number of TUNEL (3.60±3.43) (p<0.021). The tryptase signal in BOO with DO is significantly increased (19.05±6.14) (p<0.000)(Table 1). All these parameters do not show positive correlation with Abrams-Griffiths (AG) number. Increasing number of E-cadherin is associated with Pdet and Qmax. Tryptase/ mast cell is positively associated with FSF. CONCLUSIONS In this study, we have shown that LUTS secondary to BOO are associated with chronic urothelial inflammation and urothelial dysfunction. DU induced by BOO is associated with significant urothelial defection. This may imply that the loss of functional protein and urothelial cell apoptosis might contribute to the pathophysiology of bladder dysfunction in BOO. Table 1. The numbers of E-cadherin, tryptase, TUNEL and ZO-1 in different sub-groups Normal (N=10) BOO+DO (N=12) BOO+DU (N=11) BOO+HSB (N=11) P value E-cadherin 27.70±10.42 11.16±7.65 8.37±9.50 27.23±13.94 0.000 Tryptase (mast cell) 4.16±2.68 19.05±6.14 11.67±11.10 12.91±4.51 0.000 TUNEL 0.85±1.31 3.45±2.55 3.60±3.43 1.39±1.79 0.021 ZO-1 6.90±1.82 7.43±1.65 9.08±5.82 7.14±3.40 0.490 BOO: bladder outlet obstruction; DO: detrusor overactivity; DU: detrusor underactivity; HSB: hypersenstivity bladder; ZO-1: zonula occludens 1 © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e357 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chung-Cheng Wang More articles by this author Jia-Hui Chang More articles by this author Hann-Chorng Kuo More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Alteration of Urothelial Inflammation, Apoptosis, and Junction Protein in Patients with Various Bladder Conditions and Storage Bladder Symptoms Suggest Common Pathway Involved in Underlying Pathophysiology.

Lower urinary tract symptoms (LUTS) are common in various bladder disorders. This study investigated urothelial dysfunction and chronic inflammation in the urothelium in different types of lower urinary tract dysfunction (LUTD), which causes bladder storage symptoms. Bladder tissues were obtained from patients with LUTD including 17 with interstitial cystitis/bladder pain syndrome (IC/BPS), 15 with bladder outlet obstruction (BOO), 12 with spinal cord injury (SCI), 12 with recurrent urinary tract infection (UTI), 13 with ketamine related cystitis (KC) and 10 controls. The bladder specimens were investigated using immunofluorescence (IF) staining of the urothelial junction protein E-cadherin and the TUNEL assay for urothelial apoptosis. Mast cell activation was also measured by IF using tryptase for mucosal inflammation. Statistical analysis was performed using the Kruskal-Wallis and Wilcoxon rank-sum test and P-values less than 0.05 were considered significant. Highly significant increases of mast cell infiltration were observed in patients with KC (7.8 ± 3.7), IC/BPS (4.6 ± 3.0), recurrent UTI (2.4 ± 1.2), SCI (3.7 ± 2.7), and BOO (5.1 ± 2.0) compared with controls (1.3 ± 1.2) (all p < 0.05). Statistically significant increases of apoptotic cells were observed in patients with KC (4.2 ± 1.5), IC/BPS (2.4 ± 1.7), SCI (2.4 ± 1.4), recurrent UTI (1.9 ± 2.4), and BOO (1.2 ± 1.1) compared with controls (0.08 ± 0.3) (all p < 0.05). Significantly decreased expression of E-cadherin in patients with IC/BPS (25.1 ± 16.3), KC (11.0 ± 11.3), and recurrent UTI (26.2 ± 5.0) was found compared to controls (42.4 ± 16.7) and patients with SCI (44.4 ± 18.8) or BOO (42.8 ± 14.3) (all P < 0.05). Increased urothelial inflammation and urothelial cell apoptosis seem to share common pathophysiologies of various LUTDs that cause similar bladder symptoms.

Changes in nerve growth factor level and symptom severity following antibiotic treatment for refractory overactive bladder

Overactive bladder (OAB) has a multifactorial aetiology, and for some women symptoms may be associated with chronic urothelial inflammation secondary to bacterial colonisation. One marker of such inflammation may be urinary nerve growth factor (NGF). We hypothesised that for women with OAB and urothelial inflammation, urinary NGF would be reduced following antibiotic therapy. Women with overactive bladder and urodynamic diagnosis of detrusor overactivity who were refractory to anticholinergics, and had histological evidence of urothelial inflammation were treated with a 6-week course of rotating antibiotics. Urinary NGF was measured by ELISA before and after treatment. Three-day bladder diaries, the Patients' Perception of Intensity of Urgency Scale, the King's Health Questionnaire and the Patients' Perception of Bladder Condition questionnaire were used to assess subjective and objective outcomes of therapy. Thirty-nine women with refractory DO were recruited. The NGF levels decreased significantly after antibiotic therapy (Wilcoxon signed rank test; p = 0.015). There were significant improvements in daytime frequency, nocturia and urgency (p < 0.05), and 74 % of women reported improvement in perception of their bladder condition. Urinary NGF is responsive to antibiotic therapy. Women with refractory overactive bladder and elevated NGF may benefit from antibiotic treatment.

Radiation treatment of bladder squamous cell carcinoma in a patient with spina bifida: A case report

Bladder cancer is the sixth most common cancer in Canada. While most patients present with transitional cell carcinoma, few present with squamous cell carcinoma (SCC). Risk factors for SCC include a history of chronic urinary tract infection, urothelial inflammation and indwelling catheters. We present the management of a patient with locally advanced SCC of the bladder.

BK Virus Associated Hemorrhagic Cystitis in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant

Hemorrhagic cystitis (HC) is a severe complication in pediatric and adult patients (pts) undergoing allogeneic hematopoietic stem cell transplantation (HCT). HC is characterized by urothelial inflammation and painful hematuria which can be microscopic (Grade I) or macroscopic with blood clots and urinary tract obstruction (grade II-IV). The incidence of HC in pediatric HCT pts ranges from about 10% to 20 % and morbidity and mortality is as high as 75% depending on the severity of HC. The etiology of delayed onset of HC (greater than 2 weeks from conditioning therapy) is multifactorial, including damage from conditioning therapy, irradiation, graft-versus host disease (GVHD), steroids, and viral infection.