Bladder Interstitial Cystitis Research Articles

Identification of PLAC8 as a Potential Biomarker for the Diagnosis of Interstitial Cystitis.

Interstitial cystitis is a diagnosis of exclusion due to the complexity of its etiology and pathology, which is a chronic disease with an unknown etiology. To our knowledge, few studies were performed to identify predictive biomarkers for interstitial cystitis. This study aimed to identify and validate potential biomarkers for interstitial cystitis (IC). The interstitial cystitis datasets were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using the R package and were subjected to functional and pathway enrichment analysis. Key biomarkers of interstitial cystitis were identified by using Lasso regression analysis and the SVM-RFE algorithm. The diagnostic value of key biomarkers was validated in internal and external datasets, and pathways that relate to biomarkers of interstitial cystitis were screened. The ssGSEA was employed to identify the immune cells closely related to biomarkers. The expression of PLAC8 in patients with interstitial cystitis was detected by immune-histochemistry (IHC). Sixteen differentially expressed genes associated with interstitial cystitis were identified, which were primarily linked to the biological process of the chemokine signaling pathway. PLAC8, identified as a biomarker for interstitial cystitis, was validated to express a significantly different between IC and normal bladder tissues. PLAC8-related pathways were analyzed, with a focus on NF-κB, TNF, Toll-like receptor, chemokine, IL-17, and JAK-STAT signaling pathways. PLAC8 was proved to be closely related to immune activations, which is similar to the pathogenesis of IC, which is a chronic dysregulated immune disease. Meanwhile, we also observed a higher level of PLAC8 in IC tissues. PLAC8 has promising application prospects as a biomarker for interstitial cystitis diagnosis. These findings could aid in the diagnosis and treatment of interstitial cystitis.

Amitriptyline plus hydrodistension versus hydrodistension alone for treating interstitial cystitis bladder pain syndrome

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition that is difficult to diagnose and treat. The aim of this study was to investigate whether a combination treatment of amitriptyline after bladder hydrodistension is more beneficial for IC/BPS patient. Methods: Seventy-six patients’ dates diagnosed with IC/BPS were collected: the hydrodistension group (34 patients) and the combination group (42 patients), which received amitriptyline (25 mg ~ 50 mg/d) for 3 months following hydrodistension. The efficacy was evaluated at the 3rd and 6th months by using index scores. In addition, adverse events of amitriptyline and hydrodistension were recorded. Results: There was no difference in two groups at baseline. The ICSI, ICPI, AIS, SAS, OABSS, VAS and FVC scores improve significantly in the combination group than in the hydrodistension group at 3 months after hydrodistension . After 3 months of amitriptyline withdrawal, obvious improvement in the combination group was observed only for the AIS at the 6th month. At the 6th month, the indexes of the two groups still improved significantly compared with those recorded prehydrodistension; however, there was no difference in the improvement of maximum bladder volume in both groups before and after hydrodistension (P > 0.05). The adverse events of amitriptyline all were in the tolerable range. Conclusions: Hydrodistension under general anesthesia effectively relieved IC patients’ symptoms for at least 6 months. The three-month usage of amitriptyline alleviated the symptoms and problems more quickly and safely after hydrodistension in patients with IC/BPS.

Cultured versus freshly isolated adipose-derived stem cells in improvement of the histopathological outcomes in HCL-induced cystitis in a rat model

Interstitial cystitis (IC) is an incurable chronic disease. The etiology of IC is unclear, and no effective therapies have been established. Here, using a hydrogen chloride (HCL)-induced IC in a rat model, the therapeutic potency of stromal vascular fraction (SVF) and Adipose-derived stem cells (ADSCs) was studied. Thirty-six female Sprague Dawley rats were divided into four groups: the sham, HCL, (HCL+SVF) group, and (HCL+ADSCs) group (9 for each). Cystitis was induced by transurethral instillation of HCL, while PBS was used for the sham group. A single dose of SVF or ADSCs was injected into the submucosa of the rat bladder in HCL-induced IC groups. The bladder tissues were analyzed for Toluidine Blue, Masson Trichrome, CD3, and CD34 to evaluate mast cell activation, fibrosis, inflammatory cells, and bladder regeneration, respectively. Compared to HCL-induced IC, SVF or ADSCs injection into IC bladder dramatically decreased mast cell infiltration, T-cell activation, and fibrosis. Taken together, administration of SVF cells or cultured ADSCs improves the histopathological outcomes of HCL-induced bladder injury in a time-dependent manner. Of note, SVF injection into the bladder submucosa was estimated to have the most potent therapeutic efficacy and may represent an essential component in future clinical applications.

Integrating single-cell RNA sequencing with spatial transcriptomics reveals immune landscape for interstitial cystitis

Interstitial cystitis (IC) is a severely debilitating and chronic disorder with unclear etiology and pathophysiology, which makes the diagnosis difficult and treatment challenging. To investigate the role of immunity in IC bladders, we sequenced 135,091 CD45+ immune cells from 15 female patients with IC and 9 controls with stress urinary incontinence using single-cell RNA sequencing (scRNA-seq). 22 immune subpopulations were identified in the constructed landscape. Among them, M2-like macrophages, inflammatory CD14+ macrophages, and conventional dendritic cells had the most communications with other immune cells. Then, a significant increase of central memory CD4+ T cells, regulatory T cells, GZMK+CD8+ T cells, activated B cells, un-switched memory B cells, and neutrophils, and a significant decrease of CD8+ effector T cells, Th17 cells, follicular helper T cells, switched memory B cells, transitional B cells, and macrophages were noted in IC bladders. The enrichment analysis identified a virus-related response during the dynamic change of cell proportion, furthermore, the human polyomavirus-2 was detected with a positive rate of 95% in urine of patients with IC. By integrating the results of scRNA-seq with spatial transcriptomics, we found nearly all immune subpopulations were enriched in the urothelial region or located close to fibroblasts in IC bladders, but they were discovered around urothelium and smooth muscle cells in control bladders. These findings depict the immune landscape for IC and might provide valuable insights into the pathophysiology of IC.

The Effect of Chronic Psychological Stress on Lower Urinary Tract Function: An Animal Model Perspective.

Chronic psychological stress can affect urinary function and exacerbate lower urinary tract (LUT) dysfunction (LUTD), particularly in patients with overactive bladder (OAB) or interstitial cystitis–bladder pain syndrome (IC/BPS). An increasing amount of evidence has highlighted the close relationship between chronic stress and LUTD, while the exact mechanisms underlying it remain unknown. The application of stress-related animal models has provided powerful tools to explore the effect of chronic stress on LUT function. We systematically reviewed recent findings and identified stress-related animal models. Among them, the most widely used was water avoidance stress (WAS), followed by social stress, early life stress (ELS), repeated variable stress (RVS), chronic variable stress (CVS), intermittent restraint stress (IRS), and others. Different types of chronic stress condition the induction of relatively distinguished changes at multiple levels of the micturition pathway. The voiding phenotypes, underlying mechanisms, and possible treatments of stress-induced LUTD were discussed together. The advantages and disadvantages of each stress-related animal model were also summarized to determine the better choice. Through the present review, we hope to expand the current knowledge of the pathophysiological basis of stress-induced LUTD and inspire robust therapies with better outcomes.

The potential role of folate metabolism in interstitial cystitis.

The topic of interstitial cystitis (IC), also known as painful bladder syndrome (PBS), and folate/one carbon metabolism has previously been unaddressed in research. This narrative review highlights a potential connection for those with mast cell-related IC and histamine-mediated pain that is explored through four conceptual sections. The first section focuses on the nature of mast cell involvement and histamine-mediated pain in some interstitial cystitis patients. The second section reviews the literature on folate status in wider allergic conditions. The third section addresses the role of folate and methylation in general in histamine excretion. Finally, folate metabolism and vascular function are addressed because of the vascular abnormalities present in some IC bladders.

Retracted: Microrna‐139‐5p inhibits epithelial‐mesenchymal transition and fibrosis in post‐menopausal women with interstitial cystitis by targeting LPAR4 via the PI3K/Akt signaling pathway

The study explores whether miR-139-5p targeting LPAR4 affects epithelial-mesenchymal transition (EMT) and fibrosis in post-menopausal women with interstitial cystitis (IC) via the PI3K/Akt signaling pathway. Bladder tissues of IC and normal bladder tissues were collected. The pathology of bladder tissues was observed by HE, Masson and Picrosirius red staining. LPAR4 positive expression rate were determined by IHC. ELISA was performed to detect the levels of IL-6, IL-8, IL-10, and TNF-α. Rat IC models were randomized into seven different groups. miR-139-5p, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, P13K, Akt, E-cadherin, N-cadherin, Vimentin, TGF-β1, and CTGF expression were determined by RT-qPCR and Western blotting. Dual luciferase reporter gene assay verified that LPAR4 is a target gene of miR-139-5p. Fibrosis was a pathological manifestation of IC. The IC group showed higher LPAR4, PI3K, Akt, p-PI3K, p-Akt, N-cadherin, Vimentin, TGF-β1, and CTGF expression but lower miR-139-5p and E-cadherin expression than the normal group. The levels of IL-6, IL-8, IL-10, and TNF-α expression decreased while HB-EGF increased in the IC group in comparison of the normal group. Compared with the blank and NC groups, E-cadherin expression was increased in the miR-139-5p mimic and siRNA-LPAR4 groups, while LPAR4, PI3K, Akt, p-P13K, p-Akt, N-cadherin, Vimentin, TGF-β1, and CTGF expression were decreased. An opposite trend was found in the miR-139-5p inhibitor group. The miR-139-5p decreased in the miR-139-5p inhibitor + siRNA-LPAR4 and miR-139-5p inhibitor + wortmannin groups. Conclusively, miR-139-5p targeting LPAR4 inhibits EMT and fibrosis in post-menopausal IC women through the PI3K/Akt signaling pathway.

Digital quantitative analysis of mast cell infiltration in interstitial cystitis.

To evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique. Bladder biopsy specimens from 31 patients with Hunner type IC and 38 patients with non-Hunner type IC were analyzed. Bladder biopsy specimens from 37 patients without IC, including 19 non-specific chronic cystitis ("non-IC cystitis") specimens and 18 non-inflamed bladder ("normal bladder") specimens, were used as controls. Mast cell tryptase-, CD3-, CD20-, and CD138-immunoreactive cells were quantified using digital image analysis software to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and lymphoplasmacytic cell densities were counted independently in the entire lamina propria and detrusor areas and compared among the four groups. In the lamina propria, there were no significant differences in mast cell and lymphoplasmacytic cell densities between Hunner type IC and non-IC cystitis or between non-Hunner type IC and normal bladder specimens. In the detrusor, the mast cell densities were not significantly different among the four groups. Mast cell density was correlated with lymphoplasmacytic cell density, but not with clinical parameters. Mast cell density is not significantly different between IC specimens and non-IC control specimens with a similar degree of background inflammation. The intensity of mast cell infiltration generally correlated with that of lymphoplasmacytic cells. We conclude that mast cell count is of no value in the differential diagnosis between IC and other etiologies.

RETRACTED ARTICLE: Inhibition of microRNA-214 promotes epithelial–mesenchymal transition process and induces interstitial cystitis in postmenopausal women by upregulating Mfn2

Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups. Exosomes secreted by transfected ADMSCs were instilled into the bladders of postmenopausal rats. The expression of miR-214 and Mfn2 mRNA and EMT markers was assessed by qRT-PCR and western blotting. It was confirmed that Mfn2 was the target gene of miR-214 in IC. Compared with the normal bladder tissues, miR-214 decreased, but Mfn2 increased in IC bladder tissues. Compared with the blank group, the expression of miR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein increased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein decreased in the miR-214 mimics and Mfn2 groups. The expression of MiR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein decreased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein increased in the miR-214 inhibitors group. Our findings indicate that the inhibition of miR-214 promotes the EMT process and contributes to bladder wall fibrosis by up-regulating Mfn2, thus leading to the occurrence of IC in postmenopausal women.

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 < .001). The bladder IgE was greater in the patients with KC than in the others (P < .001). After excluding KC patients, bladder IgE was significantly higher in the patients with ulcerative IC than the others (P < .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 < .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

MP72-01 URINE LEVELS OF MACROPHAGE MIGRATION INHIBITORY FACTOR ARE INCREASED IN PATIENTS WITH BLADDER INFLAMMATION

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2016MP72-01 URINE LEVELS OF MACROPHAGE MIGRATION INHIBITORY FACTOR ARE INCREASED IN PATIENTS WITH BLADDER INFLAMMATION Fei Ma, Dimotrios E. Kouzoukas, Magnus M. Fall, Robert Moldwin, David M. Preston, Deborah R. Erickson, Barbara Kahn, Katherine Meyer-Siegler, and Pedro L. Vera Fei MaFei Ma More articles by this author , Dimotrios E. KouzoukasDimotrios E. Kouzoukas More articles by this author , Magnus M. FallMagnus M. Fall More articles by this author , Robert MoldwinRobert Moldwin More articles by this author , David M. PrestonDavid M. Preston More articles by this author , Deborah R. EricksonDeborah R. Erickson More articles by this author , Barbara KahnBarbara Kahn More articles by this author , Katherine Meyer-SieglerKatherine Meyer-Siegler More articles by this author , and Pedro L. VeraPedro L. Vera More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1614AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, which appears to mediate bladder inflammation and pain in rodents (Vera et al, 2010; Kouzoukas et al, 2014). We hypothesized that urinary MIF levels would increase in patients with inflammatory diseases of the bladder, and therefore examined urine from patients with conditions including: interstitial cystitis (IC) with and without Hunner lesions, urinary tract infection (UTI), and radiation cystitis. We compared these samples to those of a control population. METHODS Urine samples were collected and studied in 3 male and 3 female groups: Specimens from males included those from patients with culture confirmed UTI, those with radiation cystitis (after undergoing radiation therapy) and a control population. Specimens from females include those from IC patients with and without Hunner lesions, and those from control subjects. Urine samples from patients with Interstitial Cystitis met NIDDK diagnostic criteria. All IC patients were symptomatic at the time of urine collection. Urinary MIF and Creatinine levels were assayed using commercially available kits (R&D; Enzo). RESULTS MIF levels were significantly increased in the urine of UTI patients (>4-fold; N=51) or radiation cystitis patients (10-fold; N=18) when compared to controls (N=117), either as total concentration or normalized to creatinine levels (Table 1). Similarly, MIF levels were significantly increased (5-fold; Table 2) in the urine of IC patients with Hunner lesions (N=47) when compared to female controls (N=102). Urine MIF levels in IC patients without Hunner lesions (N=63) were not different from controls. CONCLUSIONS Urinary MIF is increased in a variety of bladder inflammatory conditions including interstitial cystitis with Hunner lesions, UTI and radiation cystitis. Conversely, urine MIF levels from IC patients without Hunner lesions are similar to controls. These findings may represent differences in pathogenesis between these conditions and may serve as a marker to distinguish them from each other. MIF may be useful for diagnosis or prognosis of IC patients with Hunner lesions and may represent a novel therapeutic target for reducing bladder pain in IC and other bladder inflammatory disorders. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e952 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Fei Ma More articles by this author Dimotrios E. Kouzoukas More articles by this author Magnus M. Fall More articles by this author Robert Moldwin More articles by this author David M. Preston More articles by this author Deborah R. Erickson More articles by this author Barbara Kahn More articles by this author Katherine Meyer-Siegler More articles by this author Pedro L. Vera More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Urethral pain syndrome: fact or fiction--an update

Urethral pain syndrome is a symptom complex including dysuria, urinary urgency and frequency, nocturia and persistent or intermittent urethral and/or pelvic pain in the absence of proven infection. These symptoms overlap with several other conditions, such as interstitial cystitis bladder pain syndrome and overactive bladder. Urethral pain syndrome may occur in men but is more frequent in women. The exact etiology is unknown but infectious and psychogenic factors, urethral spasms, early interstitial cystitis, hypoestrogenism, squamous metaplasia as well as gynecological risk factors are discussed. These aspects should be ruled out or confirmed in the diagnostic approach. Despite the assumption of a multifactorial etiology, pathophysiologically there is a common pathway: dysfunctional epithelium of the urethra becomes leaky which leads to bacterial and abacterial inflammation and ends in fibrosis due to the chronic impairment. The therapeutic approach should be multimodal using a trial and error concept: general treatment includes analgesia, antibiotics, alpha receptor blockers and muscle relaxants, antimuscarinic therapy, topical vaginal estrogen, psychological support and physical therapy. In cases of nonresponding patients intravesical and/or surgical therapy should be considered. The aim of this review is to summarize the preliminary findings on urethral pain syndrome and to elucidate the diagnostic and therapeutic options.

Anesthetic Bladder Hydrodistention Is Superior to Superior Hypogastric Plexus Neurolysis in Treatment of Interstitial Cystitis–bladder Pain Syndrome: A Prospective Randomized Trial

To evaluate efficacy and safety of superior hypogastric plexus neurolysis (SHN) for treatment of interstitial cystitis (IC)-bladder pain syndrome (BPS) in comparison with bladder hydrodistention (HD). In a prospective study, 24 female patients were randomly allocated to receive either SHN or HD. Patients were evaluated by recording the O'Leary-Sant IC symptom indices, IC problem indices, pain visual analog scale (VAS), number of daytime frequency, and nocturia. Pressure flow study was conducted for all patients. Intraoperative and postoperative changes and adverse events were recorded. Basal IC symptom indices, IC problem indices, and VAS scores were comparable between both groups (P = .31, .63, and .94, respectively). There was no statistically significant difference between both groups with respect to urodynamic parameters. Only pain VAS at first week was improved in SHN in comparison with HD (P = .012). Thereafter, all parameters were significantly improved in favor of the HD group at 2- and 4-week visits. Adverse events in both groups were ranked as Grade 1 Clavien-Dindo classification including transient hematuria in the HD group and transient back ache in the SHN group. Despite effective pain control in cases with IC-BPS after SHN, it lacks durability. It seems that SHN in its current form is not to be a suitable line of treatment for IC-BPS. Multimodality treatment would be needed for proper control of patients' symptoms.

Mesenchymal Stem Cell Therapy Alleviates Interstitial Cystitis by Activating Wnt Signaling Pathway.

Interstitial cystitis (IC) is a syndrome characterized by urinary urgency, frequency, pelvic pain, and nocturia in the absence of bacterial infection or identifiable pathology. IC is a devastating disease that certainly decreases quality of life. However, the causes of IC remain unknown and no effective treatments or cures have been developed. This study evaluated the therapeutic potency of using human umbilical cord-blood-derived mesenchymal stem cells (UCB-MSCs) to treat IC in a rat model and to investigate its responsible molecular mechanism. IC was induced in 10-week-old female Sprague-Dawley rats via the instillation of 0.1 M HCl or phosphate-buffered saline (PBS; sham). After 1 week, human UCB-MSC (IC+MSC) or PBS (IC) was directly injected into the submucosal layer of the bladder. A single injection of human UCB-MSCs significantly attenuated the irregular and decreased voiding interval in the IC group. Accordingly, denudation of the epithelium and increased inflammatory responses, mast cell infiltration, neurofilament production, and angiogenesis observed in the IC bladders were prevented in the IC+MSC group. The injected UCB-MSCs successfully engrafted to the stromal and epithelial tissues and activated Wnt signaling cascade. Interference with Wnt and epidermal growth factor receptor activity by small molecules abrogated the benefits of MSC therapy. This is the first report that provides an experimental evidence of the therapeutic effects and molecular mechanisms of MSC therapy to IC using an orthodox rat animal model. Our findings not only provide the basis for clinical trials of MSC therapy to IC but also advance our understanding of IC pathophysiology.

Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis

We analyzed the urothelium of cats diagnosed with feline interstitial cystitis to determine whether abnormalities in protein expression patterns could be detected and whether the expression pattern was similar to that in patients with human interstitial cystitis/bladder pain syndrome. The proteins analyzed are involved in cell adhesion and barrier function, comprise the glycosaminoglycan layer or are differentiation markers. Formalin fixed biopsies from 8 cats with feline interstitial cystitis and from 7 healthy control cats were labeled by immunohistochemistry and scored with a modified version of a system previously used for human samples. Cluster analysis was performed to investigate relationships between markers and samples. Of the feline interstitial cystitis bladders 89% showed abnormal protein expression and chondroitin sulfate patterns while only 27% of normal tissues showed slight abnormalities. Abnormalities were found in most feline interstitial cystitis samples, including biglycan in 87.5%, chondroitin sulfate, decorin, E-cadherin and keratin-20 in 100%, uroplakin in 50% and ZO-1 in 87.5%. In feline interstitial cystitis bladders about 75% of chondroitin sulfate, biglycan and decorin samples demonstrated absent luminal staining or no staining. Cluster analysis revealed that feline interstitial cystitis and normal samples could be clearly separated into 2 groups, showing that the urothelium of cats with feline interstitial cystitis is altered from normal urothelium. Feline interstitial cystitis produces changes in luminal glycosaminoglycan and several proteins similar to that in patients, suggesting some commonality in mechanism. Results support the use of feline interstitial cystitis as a model of human interstitial cystitis.

Mast cell activation and response to tolterodine in the rat urinary bladder in a chronic model of intravesical protamine sulfate and bacterial endotoxin-induced cystitis.

The aim of the present study was to use an animal model of interstitial cystitis (IC) in order to investigate the histology and function of the bladder, with a particular focus on mast cell degranulation and response to detrusor overactivity (DO) to tolterodine. A total of 18female Sprague‑Dawley rats were used. In 12rats, lipopolysaccharide (LPS) was intravesically instilled following the induction of IC by protamine sulfate (PS) and sixrats were subjected to sham instillations. Following 1month, cystometry was performed. The effects of tolterodine were tested in half of the animals with IC. All rats in the IC group demonstrated DO during the filling phase and no significant changes in the frequency or pressure compared with that following tolterodine injection were identified. Histological examination revealed a significant increase in the total number of infiltrated mast cells in IC rats compared with that in the sham rats (P<0.05). Degranulated mast cells were evident in 80% of rats with IC; however, they were not apparent in the sham rats. Urinary bladder inflammation, similar to that in human IC in terms of degranulated mast cells and bladder function, was induced in rats. The animal model used in the present study provided insight into the pathophysiological mechanisms underlying the ineffectiveness of anticholinergics in patients with overlapping IC and overactive bladder (OAB).

Increased Expression of Hypoxia-inducible Factor-1α and Vascular Endothelial Growth Factor Associated With Glomerulation Formation in Patients With Interstitial Cystitis

To examine whether hypoxia occurs in the bladders of patients with interstitial cystitis (IC) by monitoring the expression of hypoxia-inducible factor-1 (HIF-1) and VEGF. Previous studies have reported that bladder perfusion is decreased in patients with IC. Hypoxia induces overexpression of vascular endothelial growth factor (VEGF), which has been reported to be associated with the formation of glomerulations in patients with IC. The study group consisted of 32 patients with IC, and the control group consisted of 8 volunteers. We obtained bladder biopsies from both groups and studied the expression of HIF-1α and VEGF proteins by immunoblotting and immunohistochemical and double immunofluorescent staining. Data were analyzed using the Mann-Whitney U test. Immunoblotting and immunostaining revealed that the expression of HIF-1α and VEGF proteins was increased in the study group compared with the control group. The relative intensities of HIF-1α and VEGF proteins were 60.60 ± 7.81 and 43.60 ± 5.37 in the study group and 26.20 ± 4.72 and 20.25 ± 1.45 in the control group, respectively. The overexpression of VEGF in study group biopsies was particularly evident in umbrella cells examined by confocal microscopy. Our findings identified increased expression of HIF-1α in bladder tissue and overexpression of VEGF in umbrella cells from patients with IC. These events may be associated with glomerulation formation during hydrodistention in IC bladders. Thus, these molecular findings could offer the therapeutic mechanism for hyperbaric oxygenation application to patients with IC.

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

Changes of histamine receptors in bladder before and after the establishment of interstitial cystitis in animal model

Objective To investigate the changes of 4 histamine receptors (H1R, H2R, H2R and H4 R)in interstitial cystitis on animal experimental models. Methods Thirty female SD rats (250-300 g) were randomly divided into 2 groups as follows: 20 in experimental group and 10 in control group. The experimental group was filled with protamine sulfate+ potassium chloride to create interstitial cystitis model, the control group was sacrificed directly. At the end of the experiment, the bladders of all these SD rats were studied by the immunohistochemistry staining and the value of their mean absorbance (-A) was calculated by IPP4.5 image analysis software. The SPSS 11.5 was used to analyze the differences between the groups. Results Four kinds of histamine receptors mainly expressed in the bladder epithelium. In the experimental group, the (-A) of H1 R was 0. 054±0.031, the of H2R was 0.032±0.021, the (-A) of H3R was 0.047±0.033 and the (-A) of H4R was 0. 149±0. 191,respectively. In the control group, the A of H1R was 0. 017±0. 011, the (-A) of H2R was 0. 018±0. 015, the (-A) of H3R was 0. 014±0. 011, the (-A) of H4R was 0. 060±0.039, respectively. In contrast,the A of H1 R, H2 R and H3R in experimental group was increased significantly(P＜0.05); there was no significant change in (-A) of H4R expression(P＞0.05). Conclusions H1, H2 and H3 receptors in rat model interstitial cystitis bladder epithelium have increased and it indicates H1 R, H2R and H3R may be related to interstitial cystitis. H3 R may be a new treatment target of interstitial cystitis. Key words: Cystitis,interstitial; Urinary bladder; Receptors,histamine; Rats, SpragueDawley

Detection Of Escherichia Coli DNA From Interstitial Cystitis Bladder Biopsies Provides Little Evidence Of A Causal Microbe

Detection of Escherichia coli DNA from interstitial cystitis bladder biopsies provides little evidence of a causal microbe