Ulcerative Interstitial Cystitis Research Articles

Comparative effectiveness and safety of cocktail therapy versus combined sodium hyaluronate and chondroitin sulphate (Ialuril): Intravesical instillation treatment of interstitial cystitis/bladder pain syndrome, which one to use?

Objective: To compare effectiveness and safety of intravesical therapy (sodium hyaluronate and chondroitin sulphate) Ialuril versus cocktail therapy for treatment of interstitial cystitis (IC). Materials and methods: Prospective study from March 2013 till August 2019 including all IC patients presented to our urology clinic. All IC patients underwent basic workup including urine test, urodynamic test and gynaecological/genital exam. Postoperatively, all patients received intravesical therapy. Patients were randomly allocated to either cocktail therapy (NaOH + heparin + lidocaine) or Ialuril (Sodium hyaluronate and chondroitin sulphate) therapy as intravesical seven cycles. The primary outcome was therapy effectiveness using Interstitial Cystitis Problem Index (ICPI) and Interstitial Cystitis Symptom Index (ICSI) improvement post therapy. Secondary outcome were for complications and compliance. Results: Total of 32 patients were included (6 males, 26 females) with mean age of 43 years (24–72 years), mean follow-up 36 months (15–72 months). Cocktail intravesical therapy was used in 21 patients while 11 patients received Ialuril. All patients showed improvement on their ICSI and ICPI scores post therapy from their baseline. Statistical analysis showed no significant difference between both groups regarding improvement in ICSI and ICPI index with p-value = 0.552 and p = 0.79, respectively. Infection and non-compliance is significantly high in the cocktail arm p = 0.004, p = 0.027 Conclusions: Intravesical cocktail therapy was equally effective as Ialuril in treating IC. Ialuril was preferred over cocktail therapy because of lower side effect; when considering ulcerative IC subgroup, we need large randomised controlled trials to compare therapy benefits.

β-Defensin 2, an Antimicrobial Peptide, as a Novel Biomarker for Ulcerative Interstitial Cystitis; Can β-Defensin 2 Suspect the Dysbiosis of Urine Microbiota?

As urine is not sterile, inflammatory reactions caused by dysbiosis of the urinary microbiota may induce interstitial cystitis. A study was conducted to determine whether β-defensin 2 (BD-2), a specific antimicrobial peptide in the bladder, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC). Urine samples from three female groups were examined: healthy controls (n = 34, Control group), non-Hunner type IC (n = 40, NHIC group), and Hunner type IC (n = 68, HIC group). Urine samples were collected via a transurethral catheter and assayed for BD-2 levels using enzyme linked immunosorbent assay. Under general or regional anesthesia, cystoscopy with diagnostic and therapeutic hydrodistension was performed in NHIC and HIC groups patients. These patients underwent a biopsy of the bladders. Based on the urinary specimens from 142 patients, BD-2 expression was found to be 18-fold higher in patients with Hunner type IC than in patients with non-Hunner type IC. The enhanced secretion of BD-2 exhibited a strong correlation with increased mast cell counts associated with bladder IC pathology. Enhanced urinary secretion of the antimicrobial peptide BD-2 from Hunner type IC patients associated with clinical phenotypes and demonstrated relatively robust levels to be used as a potential biomarker. Moreover, the increased urinary level of BD-2 may suggest a new possibility of biomarkers caused by dysbiosis of the urinary microbiota in ulcerative IC.

PD01-04 ANTIMICROBIAL PEPTIDE, BETA-DEFENSIN 2 (BD2), IS A NOVEL BIOMARKER ON ULCERATIVE INTERSTITIAL CYSTITIS; CAN BD2 SUSPECT THE DYSBIOSIS OF URINE MICROBIOTA?

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (PD01)1 Sep 2021PD01-04 ANTIMICROBIAL PEPTIDE, BETA-DEFENSIN 2 (BD2), IS A NOVEL BIOMARKER ON ULCERATIVE INTERSTITIAL CYSTITIS; CAN BD2 SUSPECT THE DYSBIOSIS OF URINE MICROBIOTA? Sang Wook Lee, Woong Bin Kim, Si Hyun Kim, Ji Kang Yun, and Young Ho Kim Sang Wook LeeSang Wook Lee More articles by this author , Woong Bin KimWoong Bin Kim More articles by this author , Si Hyun KimSi Hyun Kim More articles by this author , Ji Kang YunJi Kang Yun More articles by this author , and Young Ho KimYoung Ho Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001965.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since urine is not sterile, inflammatory reactions caused by dysbiosis of urinary microbiota may induce interstitial cystitis. A study was conducted to find out whether BD2, one of antimicrobial peptides in urine, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC), compared to macrophage migration inhibitory factor (MIF). METHODS: Urine samples were assayed for BD2 and MIF by enzyme-linked immunosorbent assays (ELISA). Urine samples from three female groups were examined: healthy controls (N=34, Group I), non-ulcerative IC (N=40, Group II), and ulcerative IC (N=68, Group III). Urine samples were collected via transurethral catheter all patients with IC. Cystoscopy with diagnostic and therapeutic hydrodistention was applied a to Group II & III patients. The National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) criteria were applied to the patients with endoscopic clinical diagnosis of Painful bladder syndrome/IC. The mast cell counts criteria proposed by the European Society for the Study of Interstitial Cystitis (ESSIC) were contrasted and results were compared. RESULTS: Based on urinary specimens from a total of 142 patients, BD2 expressed 18-fold higher in patients with ulcerative IC than in patients with non-ulcerative IC. MIF levels were 31-fold higher in patients with ulcerative IC than in patients with non-ulcerative IC. The enhanced secretion of BD-2 exhibited a strong correlation with the increased mast cell counts associated with bladder IC pathology. CONCLUSIONS: Enhanced urinary secretion of BD2 from ulcerative IC patients demonstrated relatively robust levels to be used as potential biomarkers, and associated with clinical phenotypes. Moreover, the increased urinary level of anti-microbial peptide BD2 may suggest a new possibility of diagnosis caused by dysbiosis of urinary microbiota in ulcerative IC. Source of Funding: This work was supported by the “Soonchunhyang University Research Fund” © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e31-e32 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sang Wook Lee More articles by this author Woong Bin Kim More articles by this author Si Hyun Kim More articles by this author Ji Kang Yun More articles by this author Young Ho Kim More articles by this author Expand All Advertisement Loading ...

Exploration of the core genes in ulcerative interstitial cystitis/bladder pain syndrome.

ABSTRACTObjective:Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment.Materials and Methods:First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS.Results:A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained.Conclusion:The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.

Practice-changing publications in functional urology: A case-based approach.

The urological literature grows immensely by the day. Identifying practice-changing papers poses further difficulties. The purpose of this paper is to provide a common, case-based approach to applying the findings of some key papers in functional urology over the last 24 months. The cases described encompass: an elderly female with overactive bladder (OAB), a male patient with storage symptoms, a female patient with ulcerative interstitial cystitis, and a post-menopausal woman with recurrent urinary tract infections (UTI).

MicroRNA-495 alleviates ulcerative interstitial cystitis via inactivating the JAK-STAT signaling pathway by inhibiting JAK3.

As a notable chronic disorder, the incidence of interstitial cystitis (IC) has been documented to have increased among the female population with activity in microRNA-495 (miR-495) implicated in this disease. The current study was aimed at elucidating the effects associated with miR-495 on the inflammatory response and bladder fibrosis in rats with ulcerative IC via the JAK-STAT pathway by targeting JAK3. Ulcerative IC rat models were established. The targeting relationship between JAK3 and miR-495 was evaluated using luciferase reporter assay. After gain- or loss-of-function assays, mast-cell infiltration was assessed using toluidine blue staining, bladder fibrosis using Masson staining, and NO content using nitrate reductase method. JAK3 protein expression was detected by immunohistochemistry, JAK3, STAT1, STAT3, TGFβ-1, Col-I, Col-III, JAK1, JAK2, p-STAT1, and p-STAT3 expression by RT-qPCR and Western blot analysis, and serum IL-6, IL-8, IL-10, IL-17, and TNF-α levels in rats by ELISA. Following transfection of overexpressed miR-495 or siRNA-JAK3, a diminished degree of mast-cell infiltration, number of mast cells, bladder fibrosis, NO content, JAK3-positive expression, mRNA expression of JAK3, STAT1, STAT3, TGFβ-1, Col-I, Col-III, protein expression of JAK1, JAK2, JAK3, p-STAT1, p-STAT3, and expression of IL-6, IL-8, IL-10, IL-17, and TNF-α were identified. Collectively, our key findings provide evidence supporting the notion that the overexpression of miR-495 ameliorates inflammatory response and bladder fibrosis in ulcerative IC rat models via inactivation of the JAK-STAT signaling pathway by inhibiting JAK3.

Long-term outcomes of ulcerative interstitial cystitis after complete transurethral resection with therapeutic hydrodistention.

We analyzed the long-term efficacy of simultaneous transurethral resection (TUR) and therapeutic hydrodistention in patients with ulcerative interstitial cystitis (IC) who did not experience recurrence on long-term follow-up. We studied 132 female patients (mean age = 56.45 ± 11.56years) who underwent TUR followed by hydrodistention to treat ulcerative IC between January 2010 and January 2017, and who were available for follow-up, for more than 36months (mean = 52.3 ± 10.51months). Of the 132 patients, those who did not suffer recurrence within 36months after surgery were allocated to group I and those who had a recurrence within the same period were assigned to group II. Preoperative factors, including age, were compared between the groups. In group I, improvements in pain and voiding symptoms were recorded using a 10-point visual analog pain scale (VAS) and a 3-day micturition chart. A global response assessment (GRA) was used to evaluate patient satisfaction. In group II, the maximum functional bladder capacity (FBC) was smaller, and voiding frequency was higher, than in group I. Follow-up of patients in group I for more than 3years showed that pain decreased after surgery. The 10-point VAS scores were 9.68 before surgery, and 1.54, 0.93, 0.55, and 0.46 at 1, 6, 12, and 36months after surgery (p < 0.001), respectively. Maximum FBCs were 174.82mL before surgery and 237.14, 250.71, and 254.46mL at 1, 12, and 36months after surgery (p < 0.001), respectively; thus, FBC increased after surgery. Urination frequency decreased significantly after surgery; the number of daily urinations was 12.77 before surgery, and 9.88, 9.21, and 9.25 at 1, 12, and 36months after surgery (p < 0.001), respectively. Overall patient satisfaction improved after surgery; the GRA scores were 2.39, 2.71, and 2.8 points at 1, 12, and 36months after surgery (p < 0.001), respectively. Upon simultaneous performance of TUR and therapeutic hydrodistention in patients with ulcerative IC, 49.2% showed favorable outcomes for 3years.

Treatment of ulcerative compared to non-ulcerative interstitial cystitis with hyperbaric oxygen: a pilot study.

The etiology of interstitial cystitis (IC) is often idiopathic but can be due to Hunner's ulcers. Hyperbaric oxygen (HBO) is used to treat ulcerative disease of the superficial skin. We hypothesized that HBO can treat ulcerative IC (UIC) but would be less efficacious for non-ulcerative IC (NIC). Patients with NIC and UIC enrolled in this study. Following informed consent, demographic information was collected. A visual analog pain scale and validated questionnaires were collected; each patient underwent cystoscopy prior to treatment. Each subject met with a hyperbaric specialist and after clearance underwent 30 treatments over 6 weeks. Adverse events were monitored. Patients repeated questionnaires, visual analog pain scale and global response assessment (GRA) immediately, 2 weeks, 3, 6 and 12 months after treatment. Patients also underwent cystoscopy 6 months after treatment. Differences before and after treatment were compared. Nine patients were recruited to this study. One was unable to participate, leaving two subjects with NIC and six with UIC. All patients completed HBO without adverse events. Three patients completed HBO but pursued other therapies 7, 8.5 and 11 months after treatment. On GRA, 83% of patients with UIC were improved. This treatment effect persisted, as 66% of UIC patients remained better at 6 months. In contrast, only one patient in the NIC group improved. Questionnaire scores improved in both groups. Pain scores improved by 2 points in the UIC group but worsened by 1.5 points in the NIC group. Two patients with ulcers resolved at 6-month cystoscopy. HBO appeared beneficial for both UIC and NIC. Data shows slightly better benefit in patients with UIC compared to NIC; both groups showed improvement. Given the small sample size, it is difficult to draw definitive conclusions from these data. Larger studies with randomization would be beneficial to show treatment effect.

Transurethral Resection Alone Vs Resection Combined With Therapeutic Hydrodistention as Treatment for Ulcerative Interstitial Cystitis: Initial Experience With Propensity Score Matching Studies

To compare the therapeutic efficacy of transurethral resection (TUR) alone with that of TUR combined with therapeutic hydrodistention in patients with ulcerative interstitial cystitis (IC). The study subjects were 44 female patients newly diagnosed with IC who underwent TUR to treat ulcerative IC and who were available for follow-up, without recurrence of disease for 12 months. We retrospectively studied both patients who underwent TUR alone (group I) and those who underwent TUR combined with therapeutic hydrodistention (group II). Improvements in pain and voiding symptoms were retrospectively evaluated using a 10-point visual analog scale for pain and a 3-day micturition chart. Group I included 22 patients and group II included 22 patients of mean ages 58.45 ± 11.01 and 56.27 ± 11.86 years, respectively. Use of a 10-point visual analog scale showed that pain decreased after the procedures in both groups, but the improvement did not differ between groups. The maximum functional bladder capacities of patients in group I were 161.36, 192.47, and 204.12 mL, respectively, before, at 6 months, and at 12 months after the operation; the maximum functional bladder capacities of patients in group II were 175.45, 263.14, and 291.17 mL, respectively. The voiding frequencies of group I were 12.59, 10.67, and 9.89 times daily, respectively, before, at 6 months, and at 12 months after the operation; the voiding frequencies of group II were 12.95, 9.5, and 8.29 times daily, respectively. TUR combined with therapeutic hydrodistention increased bladder capacity and improved voiding symptoms more so than did TUR alone for ulcerative IC.

The Role of Immunoglobulin E in the Pathogenesis of Ketamine Related Cystitis and Ulcerative Interstitial Cystitis: An Immunohistochemical Study

Background: A previous study revealed elevated serum Immunoglobulin E (IgE) in ketamine related cystitis (KC) patients. IgE might participate the pathogenesis of different types of bladder pain syndromes, including KC and interstitial cystitis (IC). Objectives: To investigate the IgE expression in KC and IC bladder tissue. Study Design: Prospective evaluation. Setting: The study was conducted in a tertiary teaching hospital, Hualien Tzu Chi Hospital. Methods: We investigated the bladder IgE with immunofluorescence staining and quantification. The active mast cells were measuring using tryptase. The symptoms and urodynamic study results were recorded. Double immunofluorescence staining of tryptase and IgE was also performed. Sixteen KC patients, 10 ulcerative IC patients, and 20 non-ulcerative IC patients participated. The history and urodynamic parameters were investigated in these patients. The bladder mucosa was biopsied during cystoscopic hydrodistention. Bladder biopsies were also taken from 22 patients with bacterial cystitis and 12 healthy controls. Results: Bladder IgE was positive in 15 (93.8%) KC patients, 9 (90%) ulcerative IC patients, one (5%) non-ulcer IC patient, 8 (36.4%) bacterial cystitis patients, and 2 (16.7%) controls (P &lt; .001). The bladder IgE was greater in the patients with KC than in the others (P &lt; .001). After excluding KC patients, bladder IgE was significantly higher in the patients with ulcerative IC than the others (P &lt; .001). The bladder IgE was significantly correlated with pain on a visual analogue scale (r2 = 0.156, P = .017) and maximum bladder capacity (r2 = 0.423, P &lt; .001). Tryptase expression did not show a significant difference between KC, ulcer IC, and non-ulcer IC (P = 0.222). Double immunofluorescence staining showed co-expression of tryptase and IgE. Conclusions: IgE-mediated inflammation played a significant role in the pathogenesis of KC and ulcerative IC. Key words: Immunoglobulin E, ketamine cystitis, interstitial cystitis

MP72-16 SAFETY, TOLERABILITY, AND PRELIMINARY EFFICACY OF LIRIS® 400 MG IN WOMEN WITH ULCERATIVE INTERSTITIAL CYSTITIS

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2016MP72-16 SAFETY, TOLERABILITY, AND PRELIMINARY EFFICACY OF LIRIS® 400 MG IN WOMEN WITH ULCERATIVE INTERSTITIAL CYSTITIS Kenneth Peters, Yodit Seifu, Chris Cutie, and Daniel Radecki Kenneth PetersKenneth Peters More articles by this author , Yodit SeifuYodit Seifu More articles by this author , Chris CutieChris Cutie More articles by this author , and Daniel RadeckiDaniel Radecki More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1629AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ulcerative interstitial cystitis (IC) is an inflammatory bladder condition with characteristic lesions (Hunner′s lesions) noted on cystoscopy that are associated with bladder pain and voiding frequency. LiRIS is a passive, nonresorbable, intravesical system designed to provide continuous, controlled release of lidocaine into the bladder over a 2-week period. METHODS This 2-center, open-label, Phase 1b study in women ≥18 y evaluated the safety, tolerability, and preliminary efficacy of LiRIS 400 mg over two 14-day treatment periods and up to 12-weeks follow-up (Day 112). Inclusion criteria included a pain Numeric Rating Scale (NRS) score of 3-9.5, ≥1 Hunner′s lesion at screening cystoscopy, and ≥8 daily voids. A second LiRIS 400 mg was inserted at Day 14 if Hunner′s lesions appeared improved or unchanged on Day 14; it was removed on Day 28. Treatment-emergent adverse events (TEAEs), pain, voiding frequency, and O′Leary-Sant Interstitial Cystitis Symptom Index (ICSI)/Interstitial Cystitis Problem Index (ICPI) scores were recorded. RESULTS Ten patients were enrolled (mean age 57.2 y). Three patients were excluded from the analysis: 1 had only 1 LiRIS treatment, 1 expelled LiRIS prior to Day 28, and 1 did not complete follow-up. The per-protocol population thus comprised 7 patients. By Days 14 and 28, 6/7 patients (86%) and 7/7 patients (100%), respectively, responded to treatment with decreased Hunner′s lesion affected area, lesion number, and/or lesion severity. Pain NRS scores were 5.5 at baseline (BL) and decreased significantly at all time points (P<.05), including 12 weeks following LiRIS removal; decreases from BL on Days 14, 28, and 112 were -2.97 (P=.004), -4.27 (P=.003), and -4.4 (P=.029), respectively. Mean daily voids were 18.2 at BL and were reduced significantly from Day 7 through Day 56, except on Day 14 (P=.055). ICSI/ICPI scores were similarly reduced from BL at Day 20 through at least Day 56 (P<.05). No patient discontinued due to TEAEs. TEAEs occurred in 6/10 patients (2 procedure-related, 2 device-constituent-related, 1 dysuria, 1 pollakiuria). CONCLUSIONS This small proof of concept study of LiRIS 400 mg in women with ulcerative IC and Hunner′s lesions demonstrated a favorable safety profile as well as long-lasting improvements in lesions, pain, voiding frequency, and ICSI/ICPI scores. Additional double-blind, placebo-controlled studies will be necessary to confirm the safety and effectiveness of LiRIS in larger numbers of patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e958 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Kenneth Peters More articles by this author Yodit Seifu More articles by this author Chris Cutie More articles by this author Daniel Radecki More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Cystectomy for Ulcerative Interstitial Cystitis: Sequelae and Patients' Perceptions of Improvement

To evaluate the outcomes after cystectomy for ulcerative interstitial cystitis (IC). Medical records were reviewed for history, operative data, and postoperative events. A mailed survey assessed preoperative symptom severity/duration, providers seen, and symptom changes on 7-point scaled global response assessments. Descriptive statistics were performed. Of 10 women (mean age 64 ± 12.5 years), 9 had cystectomy with ileal conduit and 1 had a neobladder. All had previous cautery of Hunner's ulcer (median 3.0 cautery procedures). Maximum bladder capacity at first and last cautery was median 325 and 188 mL, respectively. Median operative time was 321 minutes, blood loss was 200 mL (range, 100-900), 4 of 10 were transfused, and length of stay was 8 days. During a mean follow-up of 3.9 years, 6 patients required 1 or more reoperations, including hernia repair (2), urostomy revision (2), revision of ureteroileal anastomosis (1), small bowel resection (1), and neobladder cutaneous fistula repair (1). Survey respondents (n= 9) reported having seen (mean) 5.4 ± 3.8 providers before cystectomy. Median duration of symptoms was 5 years, and day and nighttime urinary frequencies were 30 and 15 times, respectively. Postoperatively, IC pain had resolved in all patients except for one. On the global response assessments, patients had moderate/marked improvement in overall symptoms (8 of 8), pain (9 of 9), sexual function (4 of 6), and quality of life (8 of 9), 7 of 9 were very satisfied with the treatment, and 8 of 9 would make the same decision again. Despite subsequent reoperations, symptom improvements lead to high levels of satisfaction with cystectomy for IC.

Effect of Transurethral Resection With Hydrodistention for the Treatment of Ulcerative Interstitial Cystitis

PurposeMany treatment options to help relieve the symptoms of interstitial cystitis (IC) are available, but none are effective. Because no reports of transurethral ulcer resection with hydrodistention are available, we assessed the effects of such combined surgery for ulcerative IC.Materials and MethodsBetween June 2006 and June 2011, 87 female patients with IC who underwent transurethral resection with hydrodistention and were followed up for at least 12 months were included. Improvements in patients' voiding symptoms and pain were analyzed retrospectively by using a 3-day micturition chart and a 10-point visual analogue scale (VAS) before and after the operation. The global response assessment (GRA) was used to assess treatment satisfaction.ResultsThe mean age of the 87 female patients was 59.1±10.1 years, and the mean follow-up period was 26.7±14.4 months. Mean maximum functional bladder capacity increased from 168.4±92.4 mL to 276.3±105.4 mL (1 month) and to 227.3±91.7 mL (12 months). The mean frequency of voiding decreased from 17.2±8.5 before to 10.6±5.3 after (1 month) surgery; however, it increased again to 13.3±4.8 at 12 months. The 10-point VAS score decreased from 9.1±0.8 to 1.2±0.3 (1 month); however, it increased again to 2.5±0.4 (3 months), 3.2±0.4 (6 months), and 5.3±0.5 (12 months) (p<0.001). Symptom improvement based on the GRA was observed in 83 of the 87 patients (95.4%) at 1 month and in 55 of 87 patients (63.2%) at 12 months.ConclusionsTransurethral resection with hydrodistention is an effective treatment option for ulcerative IC because it provides improvements in voiding symptoms and pain.

Integration analysis of quantitative proteomics and transcriptomics data identifies potential targets of frizzled-8 protein-related antiproliferative factorin vivo

What's known on the subject? and What does the study add? Interstitial cystitis (IC) is a prevalent and debilitating pelvic disorder generally accompanied by chronic pain combined with chronic urinating problems. Over one million Americans are affected, especially middle-aged women. However, its aetiology or mechanism remains unclear. No efficient drug has been provided to patients. Several urinary biomarker candidates have been identified for IC; among the most promising is antiproliferative factor (APF), whose biological activity is detectable in urine specimens from >94% of patients with both ulcerative and non-ulcerative IC. The present study identified several important mediators of the effect of APF on bladder cell physiology, suggesting several candidate drug targets against IC. In an attempt to identify potential proteins and genes regulated by APF in vivo, and to possibly expand the APF-regulated network identified by stable isotope labelling by amino acids in cell culture (SILAC), we performed an integration analysis of our own SILAC data and the microarray data of Gamper et al. (2009) BMC Genomics 10: 199. Notably, two of the proteins (i.e. MAPKSP1 and GSPT1) that are down-regulated by APF are involved in the activation of mTORC1, suggesting that the mammalian target of rapamycin (mTOR) pathway is potentially a critical pathway regulated by APF in vivo. Several components of the mTOR pathway are currently being studied as potential therapeutic targets in other diseases. Our analysis suggests that this pathway might also be relevant in the design of diagnostic tools and medications targeting IC. • To enhance our understanding of the interstitial cystitis urine biomarker antiproliferative factor (APF), as well as interstitial cystitis biology more generally at the systems level, we reanalyzed recently published large-scale quantitative proteomics and in vivo transcriptomics data sets using an integration analysis tool that we have developed. • To identify more differentially expressed genes with a lower false discovery rate from a previously published microarray data set, an integrative hypothesis-testing statistical approach was applied. • For validation experiments, expression and phosphorylation levels of select proteins were evaluated by western blotting. • Integration analysis of this transcriptomics data set with our own quantitative proteomics data set identified 10 genes that are potentially regulated by APF in vivo from 4140 differentially expressed genes identified with a false discovery rate of 1%. • Of these, five (i.e. JUP, MAPKSP1, GSPT1, PTGS2/COX-2 and XPOT) were found to be prominent after network modelling of the common genes identified in the proteomics and microarray studies. • This molecular signature reflects the biological processes of cell adhesion, cell proliferation and inflammation, which is consistent with the known physiological effects of APF. • Lastly, we found the mammalian target of rapamycin pathway was down-regulated in response to APF. • This unbiased integration analysis of in vitro quantitative proteomics data with in vivo quantitative transcriptomics data led to the identification of potential downstream mediators of the APF signal transduction pathway.

Urinary Chemokines as Noninvasive Predictors of Ulcerative Interstitial Cystitis

Based on basic research findings an increase in chemokines and cytokines (CXCL-1 and 10, nerve growth factor and interleukin-6) is considered responsible for inflammation and afferent sensitization. In this cross-sectional study we tested the hypothesis that select chemokines are increased in the urine of patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome. Midstream urinary specimens were collected from 10 patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome, respectively, and from 10 asymptomatic controls. Urinary levels of 7 cytokines were measured by a human cytokine/chemokine assay. Nerve growth factor was measured by enzyme-linked immunosorbent assay. Urinary levels of most chemokines/cytokines were tenfold to 100-fold lower in asymptomatic controls vs patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome. Univariate comparison of 8 tested proteins in the ulcerative vs nonulcerative groups revealed a significant fivefold to twentyfold increase in CXCL-10 and 1, interleukin-6 and nerve growth factor (ANOVA p<0.001). Differential expression of chemokines in ulcerative and nonulcerative subtypes of interstitial cystitis/painful bladder syndrome suggests differences in paracrine signaling between the 2 entities.

Gene Expression Analysis of Urine Sediment: Evaluation for Potential Noninvasive Markers of Interstitial Cystitis/Bladder Pain Syndrome

We determined whether gene expression profiles in urine sediment could provide noninvasive markers for interstitial cystitis/bladder pain syndrome with and/or without Hunner lesions. Fresh catheterized urine was collected and centrifuged from 5 controls, and 5 Hunner lesion-free and 5 Hunner lesion bearing patients. RNA was extracted from pelleted material and quantified by gene expression microarray using the GeneChip® Human Gene ST Array. Three biologically likely hypotheses were tested, including 1) all 3 groups are distinct from each other, 2) controls are distinct from the 2 types combined of patients with interstitial cystitis/bladder pain syndrome and 3) patients with Hunner lesion-interstitial cystitis/bladder pain syndrome are distinct from controls and patients with nonHunner-lesion interstitial cystitis/bladder pain syndrome combined. For statistical parity an unlikely fourth hypothesis was included, that is patients with nonHunner-lesion interstitial cystitis/bladder pain syndrome are distinct from controls and patients with Hunner lesion-interstitial cystitis/bladder pain syndrome combined. Analysis supported selective up-regulation of genes in the Hunner lesion interstitial cystitis/bladder pain syndrome group (hypothesis 3), which were primarily associated with inflammation. The inflammatory profile was statistically similar to that reported in a prior Hunner lesion interstitial cystitis/bladder pain syndrome bladder biopsy study. Gene expression analysis of urine sediment was feasible in this pilot study. Expression profiles failed to discriminate nonHunner-lesion interstitial cystitis/bladder pain syndrome from controls and they are unlikely to be a noninvasive marker for nonHunner-lesion interstitial cystitis/bladder pain syndrome. In contrast, patients with Hunner lesion had increased proinflammatory gene expression in urine sediment, similar to that in a prior microarray study of bladder biopsies. If these preliminary results are validated in future research, they may lead to a noninvasive biomarker for Hunner lesion-interstitial cystitis/bladder pain syndrome.

Expressions of Uroplakin gene family in interstitial cystitis

Objective To detect gene expressions of Uroplakin (UP) family in interstitial cystitis (IC). Methods Gene expression of UP Ia, Ib, II, III, and III-δ4 was quantitatively measured in bladder biopsy samples from patients with IC (n=29) and control subjects (n=16) using real-time RT-PCR. Results UP III-delat4, a splicing variant of UP III, was significantly up-regulated to 4.80 in IC samples (P<0.001). When IC patients were divided into two groups, one with and one without ulcerative changes, the UP Ia, UP Ib, UP II, UP III and III-δ4 genes were significantly up-regulated to 4.99, 3.31, 2.75, 15.38, 11.48 in nonulcerative IC patients, but decreased to 0.04, 0.29, 0.09, 0.11, 0.34 in ulcerative IC patients (P<0.01). The up-regulation of UP III-δ4 was more prominent than that of UP III: 26.5-fold versus 5.6-fold compared to the median values of normal subjects. Conclusion Although the clinical implications of the over-expression of UP III and III-δ4 in non-ulcerative IC bladders remain to be clarified, from the diagnostic viewpoint, UP III-δ4 is a potential marker for identifying nonulcerative IC. Key words: Cystitis, interstitial; Uroplakin genes

Genome-based expression profiling study of Hunner’s ulcer type interstitial cystitis: an array of 40-gene model

The aim of this study was to explore potential molecular mechanisms contributing to the pathogenesis of Hunner's ulcer type interstitial cystitis (IC). Dataset acquisitions from Gene Expression Omnibus under platform accession no GSE 11783. We compared global gene expression profiles in bladder epithelial cells from IC patients with Hunner's ulcer corresponding to normal controls. We re-sampling and exploit the correlation structure presented in the dataset through the transcriptional response. For each patient, two bladder biopsies were studied, one from an ulcer area and one from a non-ulcer area. RNA was extracted, and all labeled samples were hybridized to Human Genome U133 Plus 2.0 Array (Affymetrix, CA, USA). The Mahalanobis distance in hierarchical cluster analysis revealed a model of 40 genes expression which is increased in IC and ulcerated IC. Our results can be summarized as follows: First, the expressions of major histocompatibility complex (MHC) class IF and II molecules, leukocyte immunoglobulin-like receptors, hepatitis A virus cellular receptor 2, and interleukin 32 were increased in bladder epithelial from IC and ulcerative IC area. Next, there is an indication of antigen-mediated aggregation of the high-affinity Fc epsilon and gamma RI leading to allergic inflammation through the disease status. Third, the high-affinity Fc gamma RI subunit facilitated T-cell-mediated immune response through the disease status. Such changes, jointly termed "bladder remodeling," can constitute an important long-term consequence of Hunner's ulcer type IC. Our results indicate that genome-based expression profiling can be used for the diagnostic tests of Hunner's ulcer type IC in clinical practice.

CXCR3 Binding Chemokine and TNFSF14 Over Expression in Bladder Urothelium of Patients With Ulcerative Interstitial Cystitis

We investigated the genes responsible for ulcerative interstitial cystitis by DNA microarray analysis and quantitative real-time polymerase chain reaction. Bladder urothelial tissues were taken from a site apart from the ulcerative lesion in 9 patients with ulcerative interstitial cystitis and from a normal-looking area in 9 controls, including 7 with bladder carcinoma and 2 with benign prostatic hyperplasia. Total RNA was extracted from bladder samples and gene expression was compared between these 2 groups using Whole Human Genome DNA microarray 44K (Agilent Technologies, Santa Clara, California). Microarray data were analyzed by GeneSpring GX software and Ingenuity Pathway Analysis. Chosen genes were confirmed for altered transcription by quantitative real-time polymerase chain reaction. We identified 564 probes that were significantly expressed in mRNA more than 4-fold vs those in controls using volcano plot analysis (p <0.001). Further network Ingenuity Pathway Analysis of these genes showed the top 3 functions, including 1) cell-to-cell signaling and interaction, and hematological system development and function, 2) inflammatory disease and 3) cellular development. Quantitative real-time polymerase chain reaction confirmed increased mRNA expression of several genes in the bladder samples of patients with ulcerative interstitial cystitis, including CXCR3 binding chemokines (CXCL9, 10 and 11) and TNFSF14 (LIGHT). Our study using DNA microarray analysis followed by quantitative real-time polymerase chain reaction reveals over expression of genes related to immune and inflammatory responses, including T-helper type 1 related chemokines, and cytokines such as CXCR3 binding chemokines and TNFSF14. These genes may be potential interstitial cystitis biomarkers.

Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis

BackgroundInterstitial cystitis (IC), a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed.ResultsGene expression profiles from bladder biopsies of five patients with ulcerative IC and six control patients were generated using Affymetrix GeneChip expression arrays (Affymetrix – GeneChip® Human Genome U133 Plus 2.0). More than 31,000 of > 54,000 tested probe sets were present (detection p-value < 0.05). The difference between the two groups was significant for over 3,500 signals (t-test p-value < 0.01), and approximately 2,000 of the signals (corresponding to approximately 1,000 genes) showed an IC-to-healthy expression ratio greater than two. The IC pattern had similarities to patterns from immune system, lymphatic, and autoimmune diseases. The dominant biological processes were the immune and inflammatory responses. Many of the up-regulated genes were expressed in leukocytes, suggesting that leukocyte invasion into the bladder wall is a dominant feature of ulcerative IC. Histopathological data supported these findings.ConclusionGeneChip expression arrays present a global picture of ulcerative IC and provide us with a series of marker genes characteristic for this subtype of the disease. Evaluation of biopsies from other bladder patients with similar symptoms (e.g. patients with non-ulcerative IC) will further indicate whether the data presented here will be valuable for the diagnosis of IC.