Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Association of physical therapy techniques can improve pain and urinary symptoms outcomes in women with bladder pain syndrome. A randomized controlled trial

ABSTRACT Purpose: to verify the effects of biofeedback (BF) and manual therapy (MT) associated with transcutaneous electrical nerve stimulation (TENS) or postural exercises (PE) in the treatment of bladder pain syndrome (BPS) in women regarding pain and urinary symptoms. Materials and Methods: a parallel-randomized controlled trial was conducted in BPS patients diagnosed according to NIH clinical criteria. Two specialized physiotherapists applied demographic and validated questionnaires of perineal and suprapubic pain (VAS), urinary symptoms and problems (ICSI and ICPI) and sexual function (FSFI) and a physical assessment was made to identify myofascial trigger points. Thirty-one women, mean age 51.8 ± 10.9 were randomized in three groups of treatment consisting of ten weekly sessions of BF and MT (Conventional group); BF, MT, and TENS (TENS group); and BF, MT, and PE (Postural group). Results: Postural group improved perineal and suprapubic pain after treatment (p<0.001 and p=0.001, respectively), and the suprapubic pain improvement remained persistent at 3 months of follow up (p=0.001). Postural group improved urinary symptoms and problems after treatment (p<0.001 and p=0.005, respectively) and during follow up (p<0.001 and p=0.001). Conclusions: Biofeedback and manual therapy associated with postural exercises showed a significant improvement in perineal and suprapubic pain and urinary symptoms after treatment and during follow-up. Both results suggest a possible role for the use of this physiotherapy technique to treat BPS patients. Longer follow-up and a larger number of patients are necessary to confirm these conclusions.

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

ABSTRACT Objective: 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.

A retrospective analysis of long-term follow-up of sacral neuromodulation in the management of refractory interstitial cystitis/bladder pain syndrome / 中华泌尿外科杂志

Objective:To summarize long-term outcome of sacral neuromodulation (SNM) for refractory interstitial cystitis/bladder pain syndrome (IC/BPS).Methods:Between January 2013 and October 2020, 28 patients with IC / BPS who received SNM in Beijing Chaoyang Hospital and Hebei Yanda Hospital were retrospectively analyzed. There were 5 males and 23 females, with median age 63.00 (47.50, 66.75) years old. The urgency score was 4 (3, 4) points, 24-hour micturition frequency was 26 (20.50, 32.50) times, nocturia was 9 (7, 12) times, single urine volume was 59.00 (41.25, 79.50) ml, VAS score was 9.0 (8.0, 9.0) points, O′Leary-Sant score was 31.00 (20.25, 33.00) points, and single maximum urine volume was 100.0 (80.0, 127.5) ml. The improvement of symptoms before operation, test period and last follow-up were compared.Results:The urgency score was 2 (1, 3), the 24-hour micturition frequency was 17.00 (15.00, 22.75), the frequency of nocturia was 5.5 (4.0, 7.0), the single urine volume was 87.50 (70.25, 110.00) ml, the VAS score was 4.0 (3.0, 6.0) and the O′Leary-Sant score was 20.00 (17.00, 23.00) in 28 patients during the test period, which were significantly improved compared with those before operation ( P < 0.05). There was no significant difference in the single maximum urine volume of 135.0 (102.5, 160.0) ml between the two groups ( P > 0.05). 28 patients received SNM Ⅱ permanent stimulator implantation. The median follow-up time was 29.5 (21.25, 61.75) months. Among the 28 patients, 3 patients underwent cystectomy and ileal conduit after removal of the complete SNM system due to the unsatisfied results. Twenty-five cases (89.3%) were still treated with SNM. Among them, 6 cases accepted combinative therapy of oral medicine (antihistamines, sodium pentose polysulfate, hormones, immunosuppressants, etc.). Two cases accepted combinative therapy of intravesical instillation, including heparin in one case and sodium hyaluronate in the other one. Three cases accepted combinative therapy of botulinum toxin injection.One case accepted combinative therapy of bladder augmentation. Two cases accepted combinative therapy of traditional Chinese medicine (TCM). One case accepted combinative therapy of oral medicine and TCM. The remaining 10 cases didn't accept any treatment. Among them, 3 cases were still treated with SNM even though they were not satisfied with the effect, including 1 case due to electrode displacement. At the last follow-up of 25 patients, the urgency score was 2 (1, 3), the 24-hour micturition frequency was 16.50 (13.00, 19.75), the frequency of nocturia was 5.5 (4.0, 9.0), the single urine volume was 105.0 (72.5, 120.0) ml, the VAS score was 4.5 (3.0, 6.0) and the O'Leary Sant score was 16.00 (14.00, 22.50), which were significantly improved compared with those before operation ( P < 0.05), but no difference with those during test period ( P>0.05). There was no significant difference in the single maximum urine volume of 125.0 (102.5, 150.0) ml at the last follow-up compared with preoperative and test period ( P>0.05). Conclusions:As a treatment option for refractory IC / BPS, SNM can improve the symptoms of most patients and maintain good long-term efficacy combined with other.

Therapeutic Endoscopic Treatment Plus Maintenance Dimethyl Sulfoxide Therapy Prolongs Recurrence-Free Time in Patients With Hunner Type Interstitial Cystitis: A Pilot Study / 대한배뇨장애요실금학회지

PURPOSE: To evaluate whether hydrodistention with fulguration of Hunner lesions (HD/FUL) plus maintenance dimethyl sulfoxide (DMSO) therapy prolongs the recurrence-free time in patients with Hunner type interstitial cystitis (IC).METHODS: The study enrolled patients with Hunner type IC who required repeat HD/FUL due to recurrence of IC symptoms after the first HD/FUL at our institution. All patients received a second HD/FUL plus maintenance DMSO therapy. The maintenance DMSO therapy was performed every 2 weeks for a total of 8 instillations, and then once every 4 weeks thereafter. The recurrencefree time from HD/FUL to therapeutic failure was estimated using the Kaplan-Meier method. The recurrence-free time between the first HD/FUL and second HD/FUL plus maintenance DMSO therapy was statistically compared using the log-rank test.RESULTS: A total of 21 patients (mean age, 66.3±10.8 years) with Hunner type IC were evaluated. The recurrence-free time for the second HD/FUL plus maintenance DMSO therapy was significantly longer than that for the first HD/FUL (P<0.0001). The median recurrence-free time for the first HD/FUL was 10.1 months, while that for the second HD/FUL plus maintenance DMSO therapy has yet to be reached. The recurrence-free rate for the first HD/FUL was 81.0% at 6 months, 38.1% at 1 year, 9.5% at 2 years, and 4.8% at 3 years. In contrast, the rate for the second HD/FUL plus maintenance DMSO therapy was 100% at 6 months, 94.7% at 1 year, 82.6% at 2 years, and 82.6% at 3 years. There were no significant differences in efficacy between the first and second HD/FUL.CONCLUSIONS: HD/FUL plus maintenance DMSO therapy clearly prolongs the recurrence-free time compared with HD/FUL alone in Hunner type IC.

Isolation and identification of urine-derived stem cells from female patients with interstitial cystitis/ bladder pain syndrome / 中华泌尿外科杂志

Objective To establish the method for isolation and culture of urine-derived stem cells (USCs) from female patients with interstitial cystitis/bladder pain syndrome (IC/BPS).Methods The USCs were collected from fresh midstream urine samples from 6 female IC/BPS patients admitted to our hospital from June 2018 to December 2018.The 6 patients were 33-55 years old (average 41.5 years old),and their course of illness was 2-18 years (average 8 years).The USCs were isolated from the urine through times of centrifugation and cultured in specific medium.Growth curve and cell cycle of USCs were observed.The expression of surface markers of USCs was analyzed by flow cytometry and immunofluorescence,the smooth muscle and epithelial differentiation potential of USCs were detected by immunofluorescence staining of surface markers of smooth muscle cells and epithelial cells.Results USCs were successfully extracted from 3 of 6 female patients,and the success rate reached 50％ by once extraction.USCs showed a "rice-grain" spindle appearance and showed logarithmic growth.USCs expressed surface markers associated with mesenchymal stem cells (e.g.CD44,CD73,CD105,CD133) and embryonic stem cells [e.g.stage-specific embryonic antigen 4 (SSEA4)] and pericytes[e.g.CD146,platelet derived growth factor beta receptor (PDGFRB) and NG2],but didn't express hematopoietic stem cell surface markers(e.g.CD31,CD34 and CD45).When induced to smooth muscle cells or epithelial cells,the cells expressed the surface markers of smooth muscle cells [e.g.desmin,myosin,alpha-smooth muscle actin(otSMA) and vimentin] and epithelial cells(e.g.uroplakin 1A,uroplakin 3B,AE1/AE3 and cytokeratin 13).Conclusions The method of isolation and culture of USCs from female IC/BPS patients was successfully established,and it provides a preliminary technical method for exploring the application of USCs in the clinical study of IC/BPS patients with autologous treatment.

Efficacy and safety of urinary diversion in patients with refractory interstitial cystitis/bladder pain syndrome / 中华泌尿外科杂志

Objective To evaluate the efficacy and safety of urinary diversion in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS).Methods Clinical data of 15 female patients who underwent urinary diversion treatment for IC/BPS in our hospital from January 2008 to July 2018 were retrospectively analyzed.The mean age of the subjects was 64 years old (range 29-79),and the mean disease history of IC/BPS was 5 years (range 2-15).Behavior therapy,oral medicine therapy,intravesical instillation,bladder submucosal injection of botulinum toxin type A and sacral neuromodulation showed unsatisfied outcomes in these patients.Before the surgical intervention,the average urinary frequency was (30.7 ± 11.6) per day,the median visual analogue scale (VAS) was 95 (range 50-100),the O'Leary-Sant Index was 35 (range 31-36) [all the interstitial cystitis problem index (ICPI) was 16],the pelvic pain and urgency/frequency patient symptom scale (PUF) was 35 (range 32-36) [the bother score was 12 (range 11-12)],all the quality of life (QOL) was 6,and the average serum creatinine was (81.1 ± 13.5) μmol/L.Two patients underwent cutaneous ureterostomy without cystectomy,1 patient underwent ileal conduit urinary diversion without cystectomy,and the other 12 patients underwent laparoscopic ileal conduit urinary diversion with cystectomy.The differences of the Global Response Assessment (GRA),complications,VAS,ICPI,PUF,QOL and the serum creatinine before and after the operation were compared.Results The mean postoperative follow-up period was 24 months (range 6-110).The last follow-up showed that all the GRA was 7,the median VAS was 0 (range 0-30),all the ICPI was 0,all the PUF(bother score)was 0,and the median QOL was 2 (1-4),which were significantly different with those before the surgery (all P ＜ 0.01).The last follow-up showed that the average serum creatinine was (83.8 ± 12.5)μ mol/L,which were not significantly different with that before the surgery (P =0.22).Postoperative adhesive intestinal obstruction occurred in 3 subjects.Conclusions Urinary diversion might be an effective and adequate treatment for refractory IC/BPS to eliminate pain or lower urinary tract symptom and improve quality of life of the patients.

A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis

ABSTRACT Objective To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Materials and methods Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O’Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. Results Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O’Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. Conclusions Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.

Current progress of intravesical instillation therapy in interstitial cystitis/bladder pain syndrome / 国际外科学杂志

Interstitial cystitis/bladder pain syndrome is a chronic pain syndrome characterised by pain/ discomfort attributed to the bladder,with associated urgency and urinary frequency.Its etiology is unknown and the syndrome probably have different manifestations.There is no specific treatment and multi-treatment often been used to treat interstitial cystitis/bladder pain syndrone.Bladder instillation therapy is often used as an important treatment because the drug is concentrated in the bladder and keeps a higher concentration.But the drug selection and treatment regimen of bladder instillation are not uniform.A number of intravesical agents are reviewed in this paper along with the available evidence for their use.

Research progress for the diagnosis and treatment of bladder pain syndrome/interstitial cystitis / 中国医师杂志

Bladder pain syndrome or interstitial cystitis (BPS/IC) is a clinical diagnosis based primarily on refractory suprapubic pain,which is lack of effective treatment and a broad consensus of diagnostic criteria,because its etiology and pathophysiology remains unclear.In this review,it was discussed that recent research advancement regarding to definition,etiology,diagnosis and treatment of BPS/IC,through referring to the latest guidelines and literature on this disorder.

Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research Into Interstitial Cystitis / 대한배뇨장애요실금학회지

PURPOSE: We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder. METHODS: Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis. RESULTS: In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups. CONCLUSIONS: Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.

Lupus cystitis presenting with hidronephrosis and gastrointestinal involvement / Cistite lúpica apresentando hidronefrose e envolvimento gastrointestinal

Abstract Introduction: Lupus cystitis is a rare manifestation of systemic lupus erythematosus, characterized by thickening of the bladder wall, associated with ureterohydronephrosis. In several cases gastrointestinal symptoms are the main manifestation. The optimal immunosuppressive regimen is still unknown. Methods: 16-year-old girl with systemic lupus erythematosus was admitted with dysuria, renal impairment, diarrhea, abdominal pain, nausea and vomiting. An abdominal CT scan demonstrated moderate bilateral dilation from the pelvis to the ureterovesical junction, and the bladder exhibited reduced capacity and diffusely thickened walls. A diagnosis of chronic interstitial cystitis was performed and treatment with high dose methylprednisolone resulted in a significant relief of gastrointestinal and urinary symptoms and a reduction of the bladder thickness with improvement of their capacity. Conclusion: Lupus cystitis is a rare and underdiagnosed urinary manifestation of LES and the presence of mild urinary symptoms and abdominal pain may alert about this possibility.

Resumo Introdução: A Cistite Lúpica é uma manifestação rara do Lúpus Eritematoso Sistémico, caracterizada pelo espessamento da parede da bexiga, podendo estar associada com ureterohidronefrose. Em vários casos, os sintomas gastrointestinais são a principal manifestação e ainda não se sabe qual o regime imunossupressor mais adequado nesta situação. Método: Uma jovem de 16 anos de idade com lúpus eritematoso sistémico foi admitida com disúria, insuficiência renal, diarreia, dor abdominal, náuseas e vómitos. A tomografia computadorizada de abdome demonstrou dilatação moderada de ureter e pelve renal bilateralmente e bexiga exibindo capacidade reduzida e paredes difusamente espessadas. Foi feito o diagnóstico de cistite intersticial crónica e o tratamento com dose elevada de metilprednisolona resultou em um alívio significativo dos sintomas urinários e gastrointestinais e uma redução da espessura da bexiga, com melhora da sua capacidade. Conclusão: A Cistite Lúpica é uma manifestação urinária rara e subdiagnosticada do LES e a presença de sintomas urinários leves e dor abdominal devem alertar para essa possibilidade diganóstica.

The Early Histological Effects of Intravesical Instillation of Platelet-Rich Plasma in Cystitis Models / 대한배뇨장애요실금학회지

PURPOSE: To evaluate the early histological effects of the intravesical instillation of platelet-rich plasma (PRP) in rabbit models of interstitial and hemorrhagic cystitis. METHODS: Thirty-six rabbits were classified into 6 groups: saline (S), S+PRP, hydrochloric acid (HCl), HCl+PRP, cyclophosphamide (CyP), and CyP+PRP. At 48 hours after induction, PRP was prepared and intravesically administered to the S+PRP, HCl+PRP, and CyP+PRP groups. Bladder sections were stained with toluidine blue for mast cell counting and with hematoxylin and eosin for histopathology and mitotic index determination. The proliferation index was determined by proliferating cell nuclear antigen (PCNA) immunolabeling. The nonparametric Mann-Whitney U-test was used for statistical analysis. RESULTS: No abnormalities were observed in the S group, whereas increased interstitial edema and increased average mitotic and proliferation indices were observed in the S+PRP group (P=0.023, P=0.004, and P=0.009, respectively). Intense epithelial loss, hemorrhage, and leukocyte infiltration were detected in the HCl and HCl+PRP groups, whereas a significantly increased average mitotic index was observed in the HCl+PRP group (P=0.002). When compared with its CyP counterpart, a significant reduction in hemorrhage and an increase in leukocyte infiltration and mitotic index were observed in the CyP+PRP group (P=0.006, P=0.038, and P=0.002, respectively). In addition, PCNA staining revealed a significantly increased proliferation index in the HCl+PRP and CyP+PRP groups (P=0.032 and P=0.015, respectively). CONCLUSIONS: The intravesical instillation of PRP increased the mitotic index in the saline and cyclophosphamide groups while decreasing macroscopic bleeding.

Psychological changes in patients with interstitial cystitis after hydrodistension / 中华老年医学杂志

Objective To evaluate the effect of hydrodistension on interstitial cystitis and the psychological changes after hydrodistension.Methods Thirty two patients with interstitial cystitis underwent hydrodistension from May 2011 to Jun 2012 in Department of Urology,Beijing Hospital.Interstitial cystitis symptom index(ICSI),Visual onalogue Scale (VAS) pain score,quality of life questionnaire(QOL) score,self-rating anxiety scale(SAS) score,self-rating depression scale(SDS) score were recorded and analyzed before and at 1-3 month after hydrodistension surgery.The voiding diary and postoperative complications were cared.Results Symptoms were improved in twenty nine patients,the efficiency rate was 90.6％ (29/32).There were significant differences in ICSI score,VAS pain score,QOL score,SAS score,SDS score between pre and 3 month post-surgery [(26.7± 2.3) vs.(15.2±1.9),(4.6±2.5) vs.(1.8±1.1),(4.3±2.2) vs.(2.2±1.6),(53.8±3.7) vs.(40.8±2.3),(54.8±2.3) vs.(42.4±1.5),t=8.33,7.94,6.54,7.20,8.52,respectively,all P ＜0.05].No complication was found after surgery.Both the clinical symptoms and the anxiety and depression symptoms in patients were relieved,and QOL was improved.Conclusions For the patients with interstitial cystitis,the undergoing of hydrodistension surgery can relieve the anxiety and depression symptoms and improve quality of life.

Interleukin-33 and Mast Cells Bridge Innate and Adaptive Immunity: From the Allergologist's Perspective / 대한배뇨장애요실금학회지

Interleukin (IL) 33, a member of the IL-1 superfamily, is an "alarmin" protein and is secreted in its active form from damaged cells undergoing necrotic cell death. Mast cells are one of the main effector cell types in allergic disorders. They secrete a variety of mediators, including T helper 2 cytokines. As mast cells have high-affinity IgE receptors (FcepsilonRI) on their surface, they can capture circulating IgE. IgE-bound mast cells degranulate large amounts of histamine, heparin, and proteases when they encounter antigens. As IL-33 is an important mediator of innate immunity and mast cells play an important role in adaptive immune responses, interactions between the two could link innate and adaptive immunity. IL-33 promotes the adhesion of mast cells to laminin, fibronectin, and vitronectin. IL-33 increases the expression of adhesion molecules, such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, in endothelial cells, thus enhancing mast cell adhesion to blood vessel walls. IL-33 stimulates mast cell proliferation by activating the ST2/Myd88 pathway; increases mast cell survival by the activation of survival proteins such as Bcl-XL; and promotes the growth, development, and maturation of mast cell progenitors. IL-33 is also involved in the activation of mature mast cells and production of different proinflammatory cytokines. The interaction of IL-33 and mast cells could have important clinical implications in the field of clinical urology. Epithelial dysfunction and mast cells could play an important role in the pathogenesis of interstitial cystitis. Urinary levels of IL-33 significantly increase in patients with interstitial cystitis. In addition, the number of mast cells significantly increase in the urinary bladders of patients with interstitial cystitis. Therefore, inhibition of mast cell activation and degranulation in response to increase in IL-33 is a potential therapeutic target in the treatment of interstitial cystitis.

Increased Expression of Neuregulin 1 and erbB2 Tyrosine Kinase in the Bladder of Rats With Cyclophosphamide-Induced Interstitial Cystitis / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to evaluate changes in expressions of neuregulin (NRG)1 and erbB2 tyrosine kinase (ErbB2) in bladders of rats with cyclophosphamide (CYP)-induced interstitial cystitis (IC). METHODS: Twenty-four Sprague-Dawley rats were divided into the IC group (n=16) and the control group (n=8). After inducing IC with intraperitoneal CYP injection, expressions of NRG1 and ErbB2 were analyzed using western blotting and reverse transcriptase-polymerase chain reaction. RESULTS: In Western blotting, relative intensities and distributions of both NRG1 and ErbB2 were approximately 1.5- and 3.2-fold higher, respectively, in the IC group than in the control group (mean+/-standard deviation: 1.42+/-0.09 vs. 0.93+/-0.15 and 0.93+/-0.16 vs. 0.29+/-0.08, P<0.05). In the rat bladder samples, mRNA expression levels of NRG1 and ErbB2 were higher in the IC group than in the control group (P<0.05). CONCLUSIONS: Our study has demonstrated significant changes in mRNA expression and immunoreactivity of NRG1 and ErbB2 receptors in the urinary bladder after CYP-induced IC. These results suggest that the up-regulated NRG1 may play a role in inducing an overactive bladder and promoting regeneration in the inflammatory bladder with CYP-induced IC.

Evaluation of the metabolism of glycosaminoglycans in patients with interstitial cystis

Introduction: Painful bladder syndrome/interstitial cystitis (PBS/IC) pathogenesis is not fully known, but evidence shows that glycosaminoglycans (GAG) of bladder urothelium can participate in its genesis. The loss of these compounds facilitates the contact of urine compounds with deeper portions of bladder wall triggering an inflammatory process. We investigated GAG in urine and tissue of PBS/IC and pure stress urinary incontinence (SUI) patients to better understand its metabolism. Materials and Methods: Tissue and urine of 11 patients with PBS/IC according to NIDDK criteria were compared to 11 SUI patients. Tissue samples were analyzed by histological, immunohistochemistry and immunofluorescence methods. Statistical analysis were performed using t Student test and Anova, considering significant when p < 0.05. Results: PBS/IC patients had lower concentration of GAG in urine when compared to SUI (respectively 0.45 ± 0.11 x 0.62 ± 0.13 mg/mg creatinine, p < 0.05). However, there was no reduction of the content of GAG in the urothelium of both groups. Immunofluorescence showed that PBS/IC patients had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. Conclusion: the results suggest that GAG may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the PBS/IC. .

Clinical analysis of the diagnosis and treatment of male interstitial cystitis: report of 18 cases / 中华泌尿外科杂志

ObjectiveTo investigate the diagnosis and the treatment of male interstitial cystitis (IC) to improve the efficiency.MethodsEighteen cases of IC male patients treated from Jan 2010 to Dec 2010 who suffered from suprapnbic pain urinary frequency and urgency were analyzed retrospectively.All these patients were misdiagnosed as category Ⅲ chronic prostatitis.According to the NIDDK diagnostic criteria of IC,Pelvic Pain and Urgency Frequency (PUF) scoring,potassium sensitivity test (PST),and cystoscopy under anaesthesia were used to establish the diagnosis of IC.24 h urinary diary,routine uronoscopy,prostate fluid routine and bacterial culture examination were taken before the treatment of hydrodistention and intravesical instillation of heparin.ResultsAfter the follow-up 12 to 25 months ( average,19 months),the symptoms improved distinctly.The PUF scoring was 19.2 ±4.1 before treatment and 13.6 ±2.4 after treatment respectively ( P ＜ 0.01 ).24 hours' frequency and amount of urination were (7.5 ± 4.3)times and (241.7 ±45.3) ml after treatment compared with (11.5 ±3.9) times and (159.5 ±30.8) ml before treatment ( P ＜ 0.01 ).ConclusionsThe male IC and chronic prostatitis share the same symptoms.They can be differentiated by the IC diagnosis.The treatment of hydrodistention alone with oral tolterodine tartrate sustained release tablets and intravesical instillation of heparin can evidently improve the symptoms of the male IC patients.

Role of bladder hydrodistention and intravesical sodium hyaluronate in the treatment of interstitial cystitis / 中华泌尿外科杂志

ObjectiveTo evaluate the clinical efficacy of bladder hydrodistention and intravesical sodium hyaluronate in the treatment of interstitial cystitis (IC).Methods Twenty-one IC patients received intravesical sodium hyaluronate therapy under combined blockage or intravenous anesthesia.Bladders were perfused with normal saline under 100 cm H2O perfusion pressure and expanded for 10 min,the bladders were then injected through a catheter with 40 mg/50 ml sodium hyaluronate which was released after 1 h.Intravesical perfusion was applied once every week four to six times in a course of treatment.Results The average bladder capacity was extended from 191.6 ± 88.7 ml before expansion to 425.3 ± 79.8 ml after bladder expansion ( P =0.000).The extension was done under anesthesia.There were two suspected bladder ruptures after starting the bladder expansion at 6.5 min and 7.2 min.There was significant gross hematuria in 19 cases,10 min after bladder expansion.After treatment,the catheters were removed 24 h after manipulation in 17 patients; the catheters were removed 72 h after manipulation in two cases with hematuria;the catheters were removed four days after manipulation in the two cases of suspected bladder rupture.Pain was significantly reduced after the catheters were removed and the maximum urinary output increased slightly.The day before the second injection of sodium hyaluronate,the urinary frequency decreased significantly than before start of treatment (32.8 vs 18.5 times/24 h).The maximum urinary output increased significantly compared with the output before treatment (86.7 vs 151.9 ml).Pain was reduced significantly after treatment (8.7 vs 3.0).The O'Leary-Sant IC score and the QOL were significantly improved (30.0 vs 17.0,5.9 vs 2.4,respectively) (P =0.000).After the third treatment,the symptoms continued to improve.The treatment results were best in the fifth week at the time of the sixth injection of sodium hyaluronate.Symptoms rebounded at six months.However compared with that before treatment,the difference was still statistically significant ( P =0.000).ConclusionsBladder hydrodistention under anesthesia for severe intractable IC patients produces immediate effectiveness.Sodium hyaluronic infusion can alleviate urinary frequency and pain,and the effectiveness and duration of treatment are positively correlated.

Expressions of Uroplakin gene family in interstitial cystitis / 中华泌尿外科杂志

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.