chondroitin-sulfates and Cystitis--Interstitial

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Topics: Administration, Intravesical; Botulinum Toxins, Type A; Brazil; Chondroitin Sulfates; Clinical Decision-Making; Cystitis, Interstitial; Dimethyl Sulfoxide; Diterpenes; Humans; Hyaluronic Acid; Lidocaine; Mycobacterium bovis; Pentosan Sulfuric Polyester; Treatment Outcome

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic symptom complex that may cause bothersome storage symptoms and pain or discomfort of the bladder, adversely affecting a patient's quality of life. The etiology of IC/BPS remains unclear, and its cause may be multifactorial. Diagnosis of IC/BPS is based on clinical features, and the possibility of other conditions must be ruled out first. Although no definitive treatment is currently available for IC/BPS, various intravesical therapies are used for IC/BPS, including heparin, hyaluronic acid, chondroitin sulfate, pentosan polysulfate, dimethylsulfoxide, liposomes, and botulinum onabotulinumtoxinA (BoNT-A). This review summarizes the intravesical therapy for IC/BPS and discusses recent advances in the instillation of liposomal-mediated BoNT-A and other newly developed intravesical therapies.

Topics: Acetylcholine Release Inhibitors; Administration, Intravesical; Anesthetics, Local; Anticoagulants; Botulinum Toxins, Type A; Chondroitin Sulfates; Cystitis, Interstitial; Dimethyl Sulfoxide; Free Radical Scavengers; Heparin; Humans; Hyaluronic Acid; Lidocaine; Liposomes; Pentosan Sulfuric Polyester; Urological Agents

To assess the efficacy of intravesical hyaluronic acid (HA) and HA/chondroitin sulfate (CS) instillation in patients with interstitial cystitis/painful bladder syndrome by systematic review and meta-analysis.. A systematic literature search was performed using the keywords: 'interstitial cystitis' or 'painful bladder syndrome' or 'bladder pain syndrome' and 'hyaluronic acid', up to March 31, 2016. The primary outcome was visual analogue scale related pain symptom (VAS). Secondary outcomes were the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), frequency, nocturia, bladder volume, and voided urine volume.. Ten articles involving 390 patients were retrieved and assessed in analysis. A significant improvement in mean VAS on fixed-effect and random-effect models (mean difference [MD] -3.654, 95% confidence interval [CI] -3.814 to -3.495, and MD -3.206, 95% CI -4.156 to -2.257, respectively) was found. Significant improvements were found in the ICSI (MD -3.223, 95% CI -4.132 to -2.315) and ICPI (MD -2.941, 95% CI -3.767 to -2.116). Similarly, the other outcomes were significantly improved.. Intravesical HA and HA/CS instillation improved pain symptom, quality of life, and other outcomes and could be included as therapeutic modality of interstitial cystitis/painful bladder syndrome.

Topics: Administration, Intravesical; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Hyaluronic Acid; Nocturia; Organ Size; Pain Management; Pain Measurement; Quality of Life; Treatment Outcome; Urinary Bladder

To compare the different endovesical therapeutic regimes in terms of clinical effectiveness based on glycosaminoglycan replenishment agents (RA-GAG) available on the market in Spain.. A bibliographic analysis was made of the studies published in Medline from 1996 to 2012 on RA-GAG of application in the bladder, placing emphasis on the clinical results. A post-hoc comparison was made of the efficacy of this treatment in the studies conducted in patients with interstitial cystitis in different conditions by calculating the effect sizes to analyze improvement on the pain visual analogue scale (VAS) and clinical response rate. The number of patients needed to treat (NNT) for the different agents was calculated based on the odds ratio and associated economic implications.. The globally available evidence is scarce. There are 38 articles about RA-GAGs in different indications, 71 of them in interstitial cystitis and only 8 may assist in establishing a comparison between the results presented. The treatments used were placebo, 0.8% high molecular weight hyaluronic acid (Cystistat(®)), 2% chondroitin sulfate sodium (Uracyst(®)) and a combination of 1.6% low molecular weight hyaluronic acid plus 2% chondroitin sulfate (Ialuril(®)), between 6 and 12 instillations. Another low molecular weight hyaluronic acid preparation (Uromac(®)) lacks any scientific evidence. All the therapeutic elements studied show a mean score decrease on the pain VAS and increase in the rate of post-treatment response. The NNT for the treatments that are statistically more beneficial over placebo ranges from 1.6 and 4.1. The post-hoc comparison of the response rates has established that Cystistat(®) 12 instillations (OR 18.8; 95% CI 6.4-57.2; P=.001) or 10 instillations (OR 19.2; 95% CI 5.3-75.3; P=.001) are the treatment regimes that obtain maximum effectiveness. In both cases, the NNT was 1.6.. This study has multiple limitations inherent to the nature of the design. However, although the available literature is scarce, it shows that there are differences regarding the clinical effectiveness of the different agents and regimes used for endovesical treatment of interstitial cystitis. These differences also entail economic type implications.

Topics: Chondroitin Sulfates; Cystitis, Interstitial; Glycosaminoglycans; Humans; Hyaluronic Acid

It is established that intravesical sodium hyaluronate and chondroitin sulfate has high efficacy in patients with bladder pain syndrome/interstitial cystitis (BPS/IC). Currently, an oral form of chondroitin sulfate is also available. The aim of study was to compare the efficacy of intravesical hyaluronic acid monotherapy and long-term oral chondroitin sulfate in combination with intravesical therapy in patients with BPS/IC.. A total of 59 patients with BPS/IC were randomized in two groups. In Group 1, 30 women (mean age 57.1 years) received viscoelastic solution of sodium hyaluronate 50 ml 1 time per week for 12 weeks as intravesical monotherapy. In Group 2 (n=29), patients were prescribed to complex therapy, which included the similar intravesical therapy combined with chondroitin sulfate in a dose 0.39 g, 2 capsules 3 times a day, also for 12 weeks. All patients completed visual analogue scale (VAS), interstitial cystitis symptom index (ISCI), interstitial cystitis problems index (ICPI) and voiding diary before and 1 week after the start of therapy. In all cases a cystoscopy and urodynamic study were performed in order to exclude other bladder pathologies.. At baseline, a mean VAS score in both groups was 7 points, a mean ISCI score was 17 points in Group 1 and 18 points in Group 2 (p>0.1). The mean ICPI score in both groups was 15 points. A frequency of urination in Group 1 and 2 was 11.4 and 11.6 per day, respectively (p>0,1). A mean volume of urination was 138+/-24.6 and 131+/-18.6 , respectively. After 12 weeks of therapy there was significant improvement of VAS, ICSI and ICPI scores in both groups, as well as frequency and volume of urination, but in Group 2 an improvement in almost all parameters studied, except for the volume of urination, was more pronounced.. The combined therapy of BPS/IC with intravesical hyaluronic acid and oral chondroitin sulfate provides significantly better results in comparison with intravesical hyaluronic acid as monotherapy.

Topics: Administration, Intravesical; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Hyaluronic Acid; Middle Aged; Pain; Pain Measurement

Intravesical glucosaminoglycan (GAG) replacement therapies are commonly used in the treatment of bladder pain syndrome (BPS)/interstitial cystitis (IC). Different intravesical glucosaminoglycan products are currently available. In this prospective study, clinical efficacy of chondroitin sulfate and hyaluronic acid are compared in patients with BPS/IC.. Patients were randomized to CS and HA groups. All patients were evaluated for visual analogue pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), voiding diary for frequency/nocturia, and mean urine volume per void at the beginning of the therapy and after 6 months. All patients had a potassium sensitivity test (PST) initially. Wilcoxon and Mann-Whitney U tests were used for statistical analysis.. There were 21 patients in both groups. Mean age of patients in CS and HA groups were 47.10 and 48.90, respectively(P > 0.05). Before treatment, Parson's test was positive in 64.3% of patients (27/42) with no difference between groups. VAS of pain, ICSI, ICPI, frequency at 24 h and nocturia results have improved significantly at both treatment arms. Intravesical CS was also found superior to intravesical HA in terms of 24 h frequency, nocturia and ICPI (P < 0.05). No severe adverse effects were reported.. Data comparing clinical efficiencies of different GAG therapies are very limited. In this study, intravesical CS was found superior to intravesical HA in terms of 24 h frequency, nocturia and ICPI in patients with BPS/IC in short term follow-up. To provide a definitive conclusion on superiority of one GAG therapy to others, further evaluation with long term follow up is required.

Topics: Administration, Intravesical; Adult; Aged; Chondroitin Sulfates; Cystitis, Interstitial; Female; Glycosaminoglycans; Humans; Hyaluronic Acid; Middle Aged; Nocturia; Pain; Pain Management; Pain Measurement; Prospective Studies; Treatment Outcome; Urinary Bladder Diseases; Urodynamics

Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril. Randomized, open-label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end-of-treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses.. A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P < 0.0001) in the intention-to-treat population. Treatment with HA/CS resulted in a greater reduction in pain intensity at 6 months compared with DMSO for the per-protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment-related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost-effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality-adjusted life years (QALY) and 8003€/QALY.. Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health-related quality of life, while HA/CS showed a more acceptable cost-effectiveness profile.

Topics: Administration, Intravesical; Adolescent; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Cost-Benefit Analysis; Cystitis, Interstitial; Dimethyl Sulfoxide; Female; Humans; Hyaluronic Acid; Middle Aged; Pain; Pain Measurement; Quality of Life; Treatment Outcome; Urinary Bladder; Urological Agents; Young Adult

Intravesical instillations of hyaluronic acid (HA) and chondroitin sulfate (CS) may lead to regeneration of the damaged glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome (IC/BPS).. Twenty-two patients with IC/BPS received intravesical instillations (40 ml) of sodium HA 1.6% and CS 2.0% in 0.9% saline solution (IALURIL, IBSA) once weekly for 8 weeks, then once every 2 weeks for the next 6 months.. The score for urgency was reduced from 6.5 to 3.6 (p = 0.0001), with a reduction in pain scores from an average of 5.6 to 3.2 (p = 0.0001). The average urine volume increased from 129.7 to 162 ml (p < 0.0001), with a reduction in the number of voids in 24 h, from 14 to 11.6 (p < 0.0001). The IC Symptom and Problem Index decreased from 25.7 to 20.3 (p < 0.0001), and the Pain Urgency Frequency score, from 18.7 to 12.8 (p < 0.0001).. The treatment appeared to be effective and well tolerated in IC/BPS in this initial experience.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Adult; Anti-Inflammatory Agents; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Hyaluronic Acid; Lower Urinary Tract Symptoms; Middle Aged; Pain Measurement; Surveys and Questionnaires; Urination; Urine; Young Adult

To gain additional safety and effectiveness information regarding intravesical 2% chondroitin sulfate in subjects with interstitial cystitis/bladder pain syndrome (IC/BPS) in a controlled clinical trial.. Women with IC/BPS were randomized to receive either 8 weekly bladder instillations of 20 mL of 2% chondroitin sulfate or 20 mL of inactive control solution. The primary effectiveness endpoint was the number of positive results using the Global Response Assessment at week 11 (4 weeks after the last instillation). The secondary effectiveness endpoint was a positive response to the Interstitial Cystitis Symptom Index (ICSI) at week 11. Additional effectiveness endpoints were changes from baseline at week 11 in the total ICSI score voiding diary, and visual analog scale for pain.. A total of 98 eligible women with a diagnosis of IC/BPS met the inclusion criteria and were the intention to treat population. Of the 98 women, 83% completed the study. More patients in the chondroitin sulfate group (38.0%) reported moderate or marked improvement (considered responders) compared with the inactive control group (31.3%) at the 11-week endpoint visit. Similarly, more subjects in the active treatment group were classified as ICSI and VAS pain responders and reported a greater decrease in ICSI and VAS pain scores than the control group. None of these differences were statistically significant.. Intravesical chondroitin sulfate therapy for IC/BPS might result in minor improvements in IC/BPS-related symptom and pain. However, the magnitude of benefit in our small pilot study does not support its use as monotherapy for this condition. Better strategies for selecting patients with a bladder-specific clinical phenotype might improve the overall response to this type of intravesical therapy.

Topics: Administration, Intravesical; Adult; Aged; Chondroitin Sulfates; Cystitis, Interstitial; Double-Blind Method; Female; Humans; Middle Aged; Pain Measurement; Pilot Projects; Treatment Outcome

The goal of this pilot study was to gather information on differences between intravesical chondroitin sulfate and inactive vehicle control for treatment of interstitial cystitis/painful bladder syndrome (IC/PBS).. This was a prospective, randomized, double-blind, inactive vehicle-controlled, 12-week study (6-week treatment period, followed by a 6-week follow-up period) in patients with IC/PBS. Patients were randomized to weekly intravesical treatment with 2.0% sodium chondroitin sulfate in phosphate-buffered saline or intravesical vehicle control. Primary efficacy analysis compared responders (moderately or markedly improved) according to the 7-point Global Response Assessment. Secondary endpoints include questionnaires focused on symptoms and quality of life.. Sixty-five evaluable patients were randomized. At the primary endpoint analysis (week 7), 22.6% of the vehicle control group were responders compared with 39.4% of the active therapy group (P = .15). There was no statistically significant difference for any of the secondary endpoints. Overall, 76.9% of the patients in the study reported at least 1 adverse event; most were mild or moderate, the majority associated with the vehicle control treatment. Nine nonserious intervention-related adverse events were reported in 3 patients in the vehicle control group compared with 2 in 1 patient in the active treatment group.. The difference in treatment effect in this small underpowered study was not statistically significant, although twice as many patients reported a clinically significant benefit with intravesical chondroitin sulfate treatment compared with vehicle control treatment. This trial provides data required to design a well-powered randomized vehicle-controlled trial to determine the true efficacy of this potentially promising therapy.

Topics: Administration, Intravesical; Adult; Chondroitin Sulfates; Cystitis, Interstitial; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain; Pilot Projects; Prospective Studies; Sample Size; Treatment Outcome

To report a multicentre, community based open-label study designed to assess the efficacy and safety of intravesical sodium chondroitin sulphate in the treatment of patients with the clinical diagnosis of interstitial cystitis (IC). Chondroitin sulphate is a naturally occurring glycosaminoglycan (GAG) in the bladder mucus layer and changes in this GAG have been implicated in the pathogenesis of IC, and small single-centre studies have suggested that intravesical chondroitin sulphate may have efficacy in IC.. Patients with IC were treated with sodium chondroitin sulphate (Uracyst, Stellar Pharmaceuticals Inc., London ON, Canada) solution 2.0% via urinary catheter weekly for 6 weeks and then monthly for 16 weeks for a total of 10 treatments. The primary efficacy endpoint was the percentage of responders to treatment as indicated by a marked or moderate improvement on a seven-point patient Global Response Assessment (GRA) scale at week 10 (4 weeks after the initial six treatments) compared with baseline. A major secondary efficacy endpoint (durability) was the percentage of responders on the GRA scale after 10 treatments. Additional secondary efficacy objectives were differences from baseline in Patient Symptom/Problem Index scores over the course of the treatment compared with baseline.. In all, 47% of the 53 enrolled patients with long standing moderately severe IC (mean [SD, range] diagnosis of IC 3.0 [3.4, 0.1-16] years; duration of symptoms 9.2 [9.2, 1-39] years; baseline symptom score 14.2 [3.2]) were responders at week 10. At 24 weeks, 60% were responders. There was a statistically and clinically significant decrease in the mean (SD) symptom and bother scores from baseline at 10 weeks and 24 weeks, at 9.0 (4.3) and 8.1 (5.0), respectively (P < 0.001). There were no significant safety issues during the study.. This multicentre community based real-life clinical practice study suggests that intravesical chondroitin sulphate may have an important role in the treatment of IC and validates the rationale for a randomized placebo-controlled trial.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Chondroitin Sulfates; Cohort Studies; Cystitis, Interstitial; Female; Glycosaminoglycans; Humans; Middle Aged; Potassium; Treatment Outcome; Young Adult

The aims of this study were to evaluate the efficacy and tolerability of intravesical instillations of high-molecular-weight hyaluronic acid (HA) 1.6% and chondroitin sulfate (CS) 2.0% in patients with refractory painful bladder syndrome/interstitial cystitis (PBS/IC) and to observe their impact on Quality of Life. Twenty-three women were enrolled. They received bladder instillations with HA and CS weekly for 20 weeks and then monthly for 3 months. Mean follow-up after completion of therapy was 5 months. We observed a significant improvement in urinary symptoms on voiding diaries and Visual Analogue Scale for frequency (p = 0.045), urgency (p = 0.005), and pain (p = 0.001). The O'Leary-Sant Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index resulted in a significant improvement in both scores (p = 0.004 and 0.01, respectively). The Pelvic Pain and Urgency/Frequency Symptom Scale only showed significant improvement in the symptom score (p = 0.001). This promising experience seems to offer an additional therapeutic option in patients with refractory PBS/IC.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Adult; Aged; Chondroitin Sulfates; Cystitis, Interstitial; Drug Therapy, Combination; Female; Humans; Hyaluronic Acid; Middle Aged; Pain Measurement; Quality of Life; Treatment Outcome

The aim of our study was to test the effect of a more viscous compound than existent hyaluronic acid formulation in helping to restore a defective glycosaminoglycan layer, and therefore in improving Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) symptoms when administered intravesically in IC/PBS patients.. A total of 23 female patients completed the study. Patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline, 40 ml, weekly for 12 weeks and then bi-weekly for 6 months, if there was initial response.. After 12 weeks treatment both Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), pelvic pain and Urgency/Frequency Symptom Scale (PUF) showed a mean significant improvement, which was maintained thereafter. The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks' treatment period, with a significant reduction and increase, respectively. Mean voiding volume increased from 143 ml to 191, which apparently was not reflected in a corresponding reduction of number of daily voids (from 15,5 to 14). VAS values decreased from 5,4 to 3,6 (pain) and from 6,0 to 3,5 (urgency) after the treatment cycle, showing a significant improvement.. In our preliminary experience, the administration of intravesical hyaluronic acid plus chondroitine sulphate appears to be a safe and efficacious method of treatment in IC/PBS.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Adult; Aged; Chondroitin Sulfates; Cystitis, Interstitial; Drug Therapy, Combination; Female; Humans; Hyaluronic Acid; Middle Aged; Pain Measurement; Treatment Outcome; Viscosity

Topics: Adolescent; Adult; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Inflammation; Instillation, Drug; Male; Neutralization Tests; Patient Compliance; Patient Selection; Potassium; Quality of Life; Research Design; Surveys and Questionnaires

An open label study of chondroitin sulfate was undertaken to determine the response of patients with interstitial cystitis and positive potassium test results to this agent.. Eighteen patients with classic features of interstitial cystitis were enrolled in the study. Patients received 40 mL chondroitin sulfate, 0.2% instilled intravesically once a week for four weeks and then once a month for 12 months. At the same times, Quality of Life Improvement scores, voiding diaries, and pain and voiding indices were reviewed.. Thirteen of 18 patients were followed for the entire 13-month study. Twelve of these patients responded to treatment within 3 to 12 weeks, on average. A total of 6/13 (46.2%) showed a good response, 2/13 (15.4%) had a fair response, and 4/13 (30.8%) had a partial response and 1/13 (7.7%) showed no response.. Intravesical chondroitin sulfate seems to demonstrate some beneficial effects in treatment of interstitial cystitis patients who have positive potassium stimulation test results.

Topics: Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Male

We performed a prospective, single-arm study comparing outcomes between transurethral ablation plus postoperative instillation of hyaluronic acid and chondroitin sulfate (HACS group) and transurethral ablation only in patients with Hunner type interstitial cystitis (historical control group). A total of 78 patients were enrolled, and 51 were included in the per-protocol analysis set. The 2-year recurrence rate was 47.1% (95% CI, 32.9-61.5) in the HACS group, which was significantly lower than that in the control group (86.2%; 95% CI, 74.6-93.9, P < 0.001). After instillation therapy, the hazard ratio for recurrence was 0.38 (95% CI, 0.23-0.65, P < 0.001). The HACS group had an increased recurrence-free survival with the median interval not being reached, while it was 11.4 months in the control group (95% CI, 8.8-13.8, P < 0.001). Regardless of the instillation treatment, there were significant improvements in all symptom questionnaire scores and pain compared to the baseline. However, in the instillation group, improvement was stable even after 12 months. In patients with Hunner type interstitial cystitis, intravesical instillation of hyaluronic acid and chondroitin sulfate after transurethral ablation significantly reduced the recurrence rate and maintained symptom improvement for more than 1 year.

Topics: Administration, Intravesical; Chondroitin Sulfates; Cystitis, Interstitial; Humans; Hyaluronic Acid; Prospective Studies; Treatment Outcome

To investigate the long-term feasibility, safety and effectiveness of intravesical chondroitin sulfate therapy in patients with one or more forms of chronic cystitis.. The study included 62 female patients with interstitial cystitis/painful bladder syndrome (IC/PBS) who received intravesical chondroitin sulfate (40 ml/80 mg) therapy between 2014 and 2018. A total of 15 doses of intravesical treatment were applied, once weekly in the first month and once monthly from the second month onward. A 3-day voiding diary, a visual analog scale (VAS), the O'Leary Sant Indexes (ICSI/ICPI), the Pelvic Pain and Urgency/Frequency Symptom (PPUFS) Scale and PPUF Bother scores were recorded and evaluated through prospective comparison before treatment and at the first month and first year. Patients were also assessed using the Global Response Assessment (GRA) at the end of the first month and first year to assess the effectiveness of responses to treatment.. In the first month of treatment, 0.2% chondroitin sulfate was ineffective in 22.5% of patients, with mild improvement observed in 40.0% and moderate-good improvement in 37.0%. Evaluation at the end of the first year revealed mild improvement in 21.0% of patients and moderate-good improvement in 79.0%. Statistically significant improvements were observed in all scoring systems at 1 and 12 months compared with pre-treatment values (p < 0.001).. Long-term intravesical chondroitin sulfate therapy is a safe and highly successful therapeutic modality that produces significant improvement in patients' quality of life and symptoms in the treatment of IC/PBS.

Topics: Administration, Intravesical; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Prospective Studies; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Interstitial cystitis (IC) is a progressive bladder disease characterized by increased urothelial permeability, inflammation of the bladder with abdominal pain. While there is no consensus on the etiology of the disease, it was believed that restoring the barrier between urinary solutes and (GAG) urothelium would interrupt the progression of this disease. Currently, several treatment options include intravesical delivery of hyaluronic acid (HA) and/or chondroitin sulfate solutions, through a catheter to restore the urothelial barrier, but have shown limited success in preclinical, clinical trials. Herein we report for the first time successful engineering and characterization of biphasic system developed by combining cross-linked hyaluronic acid and naïve HA solution to decrease inflammation and permeability in an in vitro model of interstitial cystitis. The cross-linking of HA was performed by 4-arm-polyethyeleneamine chemistry. The HA formulations were tested for their viscoelastic properties and the effects on cell metabolism, inflammatory markers, and permeability. Our study demonstrates the therapeutic effects of different ratios of the biphasic system and reports their ability to increase the barrier effect by decreasing the permeability and alteration of cell metabolism with respect to relative controls. Restoring the barrier by using biphasic system of HA therapy may be a promising approach to IC.

Topics: Cell Line; Chondroitin Sulfates; Cystitis, Interstitial; Humans; Hyaluronic Acid; Urothelium

To determine whether glycosaminoglycan (GAG) replenishment is able to improve recovery of a deficient urothelial barrier, chondroitin sulfate (CS) instillations were tested using an in vitro model. Porcine urothelial cells (Ucells) were terminally differentiated in culture conditions to construct a urothelial layer with a functional barrier. This layer was damaged to compromise barrier function to simulate a key characteristic of bladder pain syndrome/interstitial cystitis. The functional effect of subsequent treatment with CS was evaluated.. Primary porcine Ucells were isolated and cultured on inserts. Differentiation of cells was evaluated with immunohistochemical analysis for the presence of umbrella cells, tight junctions and CS. Transepithelial electrical resistance (TEER) measurements were performed to evaluate barrier function. Protamine was used to simulate mild urothelial damage. CS 0.2% (vol/vol), a GAG, was subsequently instilled in the treatment group. The recovery of barrier function was further evaluated with TEER measurements. The Student t test was used for the analysis of results.. After induction of differentiation, the Ucells expressed barrier markers and a functional barrier was established (measured by high TEER). TEER decreased significantly after instillation with protamine. CS instillation improved recovery of TEER significantly measured after 7 hours (84% vs 22% in controls). After 24 hours; however, the TEER was comparable in both experimental groups.. CS instillation improves the recovery of the urothelial barrier after damage in vitro. This functional experiment shows that CS improves recovery of damaged urothelial function, which supports the hypothesis behind the mechanism of action of GAG-replenishment therapy.

Topics: Animals; Cell Differentiation; Cells, Cultured; Chondroitin Sulfates; Cystitis, Interstitial; Glycosaminoglycans; Recovery of Function; Swine; Tight Junctions; Urinary Bladder Diseases; Urothelium

Our aim was to determine the efficacy of intravesical chondroitin sulfate (CS) and combined hyaluronic acid/chondroitin sufate (HA/CS) treatment and their effects on sexual function of females with interstitial cystitis/bladder pain syndrome (IC/BPS).. A total of 68 female patients with IC/BPS between 2012 and 2018 were reviewed. Thirty-three patients were treated with combined HA/CS and 28 patients were treated with CS. Instillations were performed weekly for the first month, biweekly for the second month, and monthly in the third and fourth months. Before and after the sixth month of the treatment, all patients were evaluated with the Female Sexual Function Index (FSFI), visual analog pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), and voiding diary, and changes were recorded.. A statistically significant improvement was determined for FSFI, VAS, ICSI, and ICPI scores after treatment in both groups. Among baseline characteristics, a weak but significant negative correlation was determined only between the ICSI score improvement and age (rho: -0.38; p = 0.03) on statistical analysis. Compared with CS, combined HA/CS treatment was superior in terms of ICSI, ICPI, and daytime and nighttime frequency improvement (0.042, 0.038, 0.039, and 0.045; respectively). All domains of the sexual function index were significantly improved at the sixth month of intravesical therapy in both groups. A statistical difference was not found between the two groups.. Although it seems that intravesical HA/CS combination is superior to CS alone in terms of symptom reduction, both of them have beneficial effects on sexual function.

Topics: Administration, Intravesical; Adult; Chondroitin Sulfates; Cystitis, Interstitial; Drug Combinations; Female; Humans; Hyaluronic Acid; Middle Aged; Retrospective Studies; Sexual Dysfunction, Physiological; Treatment Outcome; Young Adult

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.

Topics: Animals; Biomarkers; Cats; Cell Differentiation; Chondroitin Sulfates; Cystitis, Interstitial; Disease Models, Animal; Humans; Immunohistochemistry; Proteins; Urothelium

Aim of the study was to validate the Hyaluronic acid-Chondroitin sulfate (HA-CS) as ex adiuvantibus criteria to identified patients with urgency symptoms related to interstitial cystitis/painful bladder syndrome (IC/PBS) and to obtained a population of patients with pure stress urinary incontinence.. We retrospectively analysed clinical data of 17 patients with clinical suspect of IC/PBS, which received intravescical HA-CS to reduce pelvic pain and urgency symptoms waiting for surgical treatment for stress urinary incontinence. The main outcomes were reduction of urinary frequency, urgency, and bladder pain.. Compared to baseline, a significant decrease in pain, urgency and frequency were observed. Of the 17 patients, 82.3% reported resolution of pain and urge symptoms and in patients with persistence of urge symptoms the urodynamic assessment showed an overactive bladder syndrome (OAB).. HA-CS treatment induces an improvement in pain and urgency symptoms in patients with IC⁄PBS that referred also stress urinary incontinence. Therefore, HA-CS treatment could be use as clinical adjunctive parameter to select patients with pure stress urinary incontinence.

Topics: Adult; Chondroitin Sulfates; Cohort Studies; Cystitis, Interstitial; Drug Combinations; Female; Humans; Hyaluronic Acid; Middle Aged; Pelvic Pain; Retrospective Studies; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Stress; Urinary Incontinence, Urge; Urodynamics; Young Adult

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory condition of the bladder. Bladder instillation is one avenue of treatment but evidence for its effectiveness is limited. Chondroitin sulphate solution 2.0% (Urocyst) is a glycosaminoglycan (GAG) replenishment therapy instilled for patients with IC/PBS. We assessed its effectiveness for treating IC/PBS in Northern Ireland.. Patients with IC/PBS were assessed with the O'Leary-Sant interstitial cystitis index score and global response assessment questionnaire prior to commencing treatment. Assessment with these questionnaires was performed after 6 treatments (10 weeks) and again after 10 treatments (24 weeks). Assessment end points were pain, urgency, symptom score and problem score.. Data was collected on 10 patients, 9 female and 1 male. 6 patients had failed RIMSO-50 dimethyl sulphoxide (DMSO) 50% treatment prior. At baseline the mean pain score was 6.6, urgency score 7.00, symptom score 13.5 and problem score 12.5. After 24 weeks the mean pain score fell to 2.0, urgency score to 1.80, symptom score to 6.89 and problem score to 5.67. At 10 weeks the global response to treatment was 100%. Nocturia was the first symptom to improve with urgency and pain following. No side effects were noted during instillation and all patients tolerated the treatments.. IC/PBS is a difficult disease to treat. It requires a multimodal approach. We found that intravesical chondroitin sulphate reduced pain, urgency and O'Leary-Sant symptom and problem scores in patients with IC/PBS. All patients tolerated the treatment and no side effects were reported.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome

To investigate beneficial effect of the readily available colchicine through its intravesical application on protamine/lipopolysaccharide induced interstitial cystitis model in rat and to compare its efficacy to the chondroitin sulphate available for clinical use.. Twenty-four Wistar female rats were assigned to control (C), interstitial cystitis (IC), chondroitin sulphate (CS) and colchicine (Col) groups. IC, CS and Col groups received protamine sulphate and lipopolysaccharide (PS/LPS) instillation. Testing agents CS and Col were administered a day after PS/LPS inoculation into the bladders. Rats in Group C received saline solution. CS and Col groups received 1 mL CS (0.2%) and 1 mL Col (0.05 mg/mL). The treatment agents were left in bladders for one hour's duration. Animals were sacrificed 5 days after the inoculation and the bladder tissues were examined histologically to evaluate the amount of extravasated leucocytes, mast cell concentration (by counting total number of cells per 10 high power field (hpf; 1 hpf = ×400 magnification) as well as interstitial tissue edema for each bladder.. Intravesical application of CS reduced significantly the leucocyte and mast cell infiltration as well as interstitial edema compared to group C . The level of reduction in leucocyte and mast cell infiltration in Col group was comparable to that of CS, although the interstitial edema was not resolved.. Intravesical administration of Col decreased leucocyte and mast cell infiltration to the same extent of CS in PS/LPS induced bladder inflammation in rat. Col may be an alternative to other treatment modalities for painful bladder conditions such as IC.

Topics: Administration, Intravesical; Animals; Chondroitin Sulfates; Colchicine; Cystitis; Cystitis, Interstitial; Disease Models, Animal; Female; Lipopolysaccharides; Protamines; Rats; Rats, Wistar

To investigate what changes are endoscopically evident after glycosaminoglycans (GAGs) therapy by hyaluronic acid (HA) and chondroitin sulphate (CS) (Ialuril®) in female patients affected by bladder pain syndrome(BPS)/ interstitial cystitis (IC) or recurrent urinary tract infections (rUTIs).. 21 female patients over 18 years affected by rUTIs or BPS/IC received intravesical instillation of HA and CS (4 weekly instillations followed by 2 instillations every 2 weeks and 2 instillation monthly). Post-treatment evaluation included cystoscopy and patient assessment of improvement in symptoms and satisfaction on a visual analogue scale (VAS) from 0 to 10.. The post-treatment endoscopy showed a positive effect on bladder mucosa morphology. In 2 cases, treatment did not change endoscopic findings and clinical symptoms. In the other patients, when macroscopic features of the bladder mucosa normalized, the clinical picture improved.. GAGs therapy by HA and CS (Ialuril) improves the morphology of bladder mucosa in patients with rUTI or BPS/IC.

Topics: Adult; Aged; Chondroitin Sulfates; Cystitis; Cystitis, Interstitial; Cystoscopy; Drug Combinations; Endoscopy; Female; Glycosaminoglycans; Humans; Hyaluronic Acid; Middle Aged; Mucous Membrane; Urinary Bladder; Urinary Bladder Diseases; Urinary Tract Infections; Urothelium

To assess the response of patients diagnosed with painful bladder syndrome to treatment with instillations of sodium chondroitin sulfate.. We present a series of cases of patients with painful bladder syndrome who followed a bladder instillation protocol with sodium chondroitin sulfate, according to our centre's regimen. The response to treatment was assessed with respect to pain, according to the Downie scale; urinary frequency, according to the voiding diary; and subjective improvement, according to the Patient Global Impression of Improvement (PGI-I) scale.. A total of 28 patients with a median age of 59 years (range 22-90) followed this protocol. From the medical histories, 19.4% had suffered an infection of the urinary tract, 3.8% had suffered urinary tuberculosis, 7.6% received pelvic radiation therapy and 26.9% had taken anticholinergic drugs for overactive bladder syndrome. We evaluated the response to treatment at 0, 3, 6 and 12 months and found that at the end of treatment 72.3% of the patients had improved bladder pain and 75% were significantly better.. Treatment with sodium chondroitin sulfate through endovesical instillation in painful bladder syndrome improves pain, voiding frequency and quality of life in the long term.

Topics: Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Male; Middle Aged; Young Adult

Topics: Administration, Intravesical; Anti-Inflammatory Agents; Chondroitin Sulfates; Cystitis, Interstitial; Humans; Hyaluronic Acid

Topics: Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans

Reconstruction of the glycosaminoglycan layer plays a role in the successful treatment of bladder pain syndrome/interstitial cystitis (BPS/IC). Intravesical instillations of hyaluronic acid (HA) and chondroitin sulphate (CS) have given results in the short term. We hypothesise that these benefits continue in the longer term.. With the aim of evaluating this therapy over a longer period we treated 12 BPS/IC patients refractory to other treatments with a combination of HA 1.6 % and CS 2.0 % over a period of 3 years assessing symptoms and quality of life using a visual analogue scale, 3-day voiding diaries and validated questionnaires.. Improvements in bladder function were sustained for 3 years (mean number of daily voids decreased from 17.8 at baseline to 15.5 at 9 months and 11.9 at 3 years, and mean volume per void from 136.8 ml at baseline to 143.9 ml at 9 months and 180.9 ml at 3 years). Quality of life assessments confirmed these improvements.. Intravesical instillations of HA and CS produced a sustained improvement of the symptomatology, up to 3 years, in patients with BPS/IC refractory to previous treatments. Further confirmation would be expected from larger controlled trials.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Adult; Aged; Anti-Inflammatory Agents; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Hyaluronic Acid; Longitudinal Studies; Middle Aged; Pain Measurement; Quality of Life; Surveys and Questionnaires; Time Factors; Urination

Urothelial glycosaminoglycans (GAGs) are decreased in bladder pain syndrome (BPS), and urinary GAGs are thought to reflect this deficiency. In previous researches, urine GAG levels were found increased, decreased, or similar between BPS and controls. Additionally, no study is available on the structure characterization of urinary chondroitin sulfate (CS) in BPS patients.. CS in the urine of BPS-affected patients and controls has been determined by specific electrophoresis, along with total GAGs and heparan sulfate (HS) percentage, and CS disaccharides have been quantified by high-performance liquid chromatography.. No significant differences were obtained for total amount of GAGs, absolute content of CS and HS, and their relative percentages. Moreover, no differences were observed for CS structure confirming similar urine CS composition in BPS subjects and controls.. This study found no significant differences of BPS and control urine GAG levels and CS structure to allow use of these parameters as diagnostic markers for BPS diagnosis.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Cystitis, Interstitial; Electrophoresis, Agar Gel; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Middle Aged

Interstitial cystitis and BPS (bladder pain syndrome) are chronic inflammatory diseases of the bladder. They are as yet imperfectly understood diseases, possibly originating from damage to the glycosaminoglycan layer of the bladder epithelium . Hyaluronic acid-containing preparations are currently utilised for palliation of the symptoms and protection of the bladder epithelium . The aim of the work described here was the evaluation of one of these preparations containing chondroitin sulfate together with hyaluronic acid.. The preparation was evaluated for its anti-inflammatory potential as well as regarding the tolerance by the bladder epithelium. The urothelial cell line T24 was employed as an in vitro model of the human bladder because of its ability to react to adequate stimuli with the release of interleukin 6. To this end the cells were treated with hyaluronic acid and chondroitin sulfate. Subsequently, TNF-alpha was applied to induce inflammation. The severity of inflammation was measured on the basis of the IL-6 released by the cells in comparison to untreated control cultures.. A reduction of TNF-alpha-induced IL-6 release after treatment with hyaluronic acid and chondroitin sulfate was observed, indicating the anti-inflammatory action of the preparation. As shown by the large number of living cells after treatment the test preparation did not affect cell viability even in high concentrations. These data suggest a good tolerance of the product by the patients.. The administration of the preparation in patients suffering from interstitial cystitis or BPS appears promising. In additional, the presented work demonstrates the feasibility of the cell culture model for the screening of new therapeutic approaches.

Topics: Adjuvants, Immunologic; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cell Survival; Chondroitin Sulfates; Cystitis, Interstitial; Dose-Response Relationship, Drug; Escherichia coli; Feasibility Studies; Humans; Hyaluronic Acid; In Vitro Techniques; Interleukin-5; Lipopolysaccharides; Tumor Necrosis Factor-alpha; Urothelium

Effectiveness, safety, and tolerability of instillation therapy with chondroitin sulphate (CAS 9082-07-9, Gepan instill) was investigated in a non-interventional study. 286 patients with clinically diagnosed chronic forms of cystitis, such as bladder pain syndromelinterstitial cystitis, radiation cystitis, overactive bladder syndrome and chronically-recurring cystitis were included. The course of symptoms was documented over 8 instillations at maximum, covering a period of approximately three months. All main symptoms of chronic cystitis declined consistently and statistically significantly (p < 0.0001). Both daytime and nighttime micturition frequencies as well as the score levels of urgency and pain declined significantly during the course of treatment. The functional bladder capacity as indicated by the volume of first morning voiding increased from 157.9 ml +/- 7.5 to 186.7 ml +/- 6.9 (mean +/- SE; p < 0.0001). The level of urgency decreased from 6.8 +/- 0.1 to 3.4 +/- 0.2 (mean +/- SE; numerical rating scale (11-point box scale); p < 0.0001) and nocturia decreased from 4.0 +/- 0.2 to 2.1 +/- 0.1 times (mean +/- SE; p < 0.0001). Chondroitin sulphate instillation was effective and well tolerated in the therapy of chronic forms of cystitis associated with a possible GAG layer deficit (GAG layer: mainly composed of the glycosaminoglycans chondroitin sulphate, dermatan sulphate and heparan sulphate), but the results need to be confirmed in a controlled study.

Topics: Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Chronic Disease; Cystitis; Cystitis, Interstitial; Female; Glycosaminoglycans; Humans; Injections; Male; Middle Aged; Pain; Pain Measurement; Prospective Studies; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics

Interstitial cystitis/Painful bladder syndrome (IC/PBS) is a chronic bladder condition of unknown etiology and pathogenesis. However, there is evidence of bladder surface mucosal and glycosaminoglycans (GAG) dysfunction in IC/PBS and GAG replacement therapy has been used to treat the condition. The results of an open label, uncontrolled study of a dietary supplement designed to improve GAG mucopolysaccharides integrity (glucosamine sulfate, sodium hyaluronate and chondroitin sulfate) and reduce bladder wall inflammation (quercetin, rutin) are presented herein.. Two hundred fifty two IC/PBS patients (25 men, 227 women; 18-69 years old), who had failed other treatments, took four CystoProtek capsules /day (mg/capsule: glucosamine sulfate, 120; chondroitin sulfate, 150; hyaluronate sodium, 10; quercetin, 150; rutin, 20). Symptoms were evaluated using a visual analogue scale (VAS) (severity range from 1-10) before and after treatment (< 6, 6-12 or > 12 months). The women were divided into two severity groups--a more severe A group with a baseline mean VAS score greater than or equal to 5 and a less severe B group with a mean score < 5.. Male patients (55.72 +/- 9.53 years, n = 25) had a mean VAS score at baseline of 7.6 +/- 1.63 which fell 51.8% to 3.94 +/- 2.46 (p < 0.0001) after 12.46 +/- 8.76 months of treatment. The women (n = 227) experienced a 48.8% reduction in the mean VAS score (p < 0.0001) after 11.2 +/- 8.7 months. The mean VAS score in Group A (49.72 +/- 11.39 years, n = 207) fell 52.1% from 7.91 +/- 1.55 to 3.79 +/- 2.37 (p < 0.0001) after 11.06 +/- 8.18 months and in Group B (52.40 +/- 10.19 years, n = 20) fell 43.5% from 3.15 +/- 0.92 to 1.78 +/- 1.63 (p = 0.013) after 10.10 +/- 5.80 months. Patients in Group A and B were further subdivided into Groups A1, B1 (> 12 months), A2, B2 (6-12 months) and A3, B3 (< 6 months treatment); improvement was statistically significant in all the more severe Group A treatment duration subgroups.. Dietary supplements targeting the bladder GAGs (chondroitin, glucosamine, hyaluronate) and bladder inflammation (quercetin, rutin) are useful in the treatment of refractory IC/PBS. Prospective randomized trials of such supplements are warranted in both treatment refractory and treatment naïve patients.

Topics: Adolescent; Adult; Aged; Chondroitin Sulfates; Cystitis, Interstitial; Dietary Supplements; Drug Combinations; Female; Humans; Hyaluronic Acid; Male; Middle Aged; Young Adult

(1) Chondroitin sulfate solution 2.0% is a glycosaminoglycan (GAG) replenishment therapy instilled into the bladder of GAG-deficient patients with interstitial cystitis (IC). (2) Two non-randomized, uncontrolled pilot studies report improvements in patient-reported symptoms after the use of chondroitin sulfate for one year. Prospective, randomized, head-to-head trials are needed to assess the effectiveness of this technology compared with other IC therapies. (3) The cost and demand for this technology are low, but there could be a significant impact on clinics that administer treatment, if uptake increases.

Topics: Canada; Chondroitin Sulfates; Costs and Cost Analysis; Cystitis, Interstitial; Evidence-Based Medicine; Female; Humans; Male

Interstital cystitis is often treated with exogenous glycosaminoglycans such as heparin, chondroitin sulphate (Uracyst), hyaluronate (Cystistat) or the semi-synthetic pentosan polysulphate (Elmiron). The mechanism of action is presumed to be due to a coating of the bladder surface to replace the normally present chondroitin sulphate and heparan sulphate lost as a result of the disease. This study used fluorescent labelled chondroitin sulphate to track the distribution of glycosaminoglycans administered intravesically to mouse bladder that had been damaged on the surface.. The surfaces of mouse bladders were damaged by 3 mechanisms -- trypsin, 10 mM HCl, and protamine sulphate. Texas Red-labeled chondroitin sulphate was instilled into the bladders of animals with damaged bladders and controls instilled only with saline. Bladders were harvested, frozen, and sectioned for examination by fluorescence.. The normal mouse bladder bound a very thin layer of the labelled chondroitin sulphate on the luminal surface. Trypsin- and HCl-damaged bladders bound the labelled chondroitin sulphate extensively on the surface with little penetration into the bladder muscle. Protamine produced less overt damage, and much less labelling was seen, presumably due to loss of the label as it complexed with the protamine intercalated into the bladder surface.. Glycosaminoglycan administered intravesically does bind to damaged bladder. Given that the changes seen following bladder damage resemble those seen naturally in interstitial cystitis, the mechanisms proposed for the action of these agents is consistent with a coating of damaged bladder.

Topics: Animals; Chondroitin Sulfates; Cystitis, Interstitial; Fluorescent Dyes; Glycosaminoglycans; Mice; Mice, Inbred C57BL; Urinary Bladder; Xanthenes

Despite a lack of consensus concerning the etiology of interstitial cystitis (IC) the loss of impermeability and other abnormalities of the urothelium are features of the disease. In this study the distribution of proteins involved with epithelial adhesion, cellular differentiation and bladder impermeability in urothelial biopsies were explored by the immunohistochemical assessment of E-cadherin, ZO-1, uroplakin and chondroitin sulfate.. Biopsies obtained from 27 patients with IC and 7 controls were immediately fixed in formalin, immunohistochemically labeled for the described proteins and scored for protein expression, morphology and differentiation.. Only 3 IC samples appeared completely normal, while 24 of the 27 showed an abnormality in at least 1 marker and in 6 all 4 markers were abnormal. In patients vs controls findings were abnormal for uroplakin in 13 of 27 vs 1 of 7 (p = 0.085), for E-cadherin (over expressed) in 18 of 27 vs 0 of 7 (p = 0.0021), for ZO-1 in 11 of 27 vs 0 of 7 (p = 0.046) and for chondroitin sulfate in 15 of 27 vs 0 of 7 (p = 0.0054). The morphology/polarity score significantly correlated with ZO-1 (Pearson r = 0.3935, p = 0.0423) and chondroitin sulfate (Pearson r = 0.7079, p <0.0001) expression. Chondroitin sulfate and ZO-1 showed a high correlation with each other (Pearson r = 0.5587, p = 0.0025). Uroplakin and E-cadherin expression were independent of all other markers.. The findings reported strongly suggest abnormal differentiation in the IC bladder. The disruption of ZO-1 is similar to that reported in feline IC. Elevated E-cadherin may represent an adaptation to increased bladder permeability.

Topics: Adult; Aged; Antibodies, Monoclonal; Biomarkers; Cadherins; Chondroitin Sulfates; Cystitis, Interstitial; Female; Humans; Male; Membrane Proteins; Middle Aged; Urinary Bladder; Uroplakin II; Urothelium

Mast cells are ubiquitous cells derived from the bone marrow and are responsible for allergic reactions as they release numerous vasodilatory, nociceptive and pro-inflammatory molecules in response to immunoglobulin E (IgE) and specific antigen. Mast cell secretion is also triggered by a number of peptides, such as bradykinin and substance P, and may also be involved in the development of inflammatory responses. An example is interstitial cystitis, which is a sterile painful bladder disorder that has been associated with a defective glycosaminoglycan bladder mucosal layer and an increased number of activated mast cells. Pentosanpolysulfate is a synthetic, sulfated polysaccharide that has been approved for the treatment of interstitial cystitis on the premise that it may replenish the defective glycosaminoglycan layer. We hypothesize that pentosanpolysulfate may also have an additional or alternate action on bladder mast cells. We report that pentosanpolysulfate has a powerful dose dependent inhibitory effect on mast cell release of histamine induced by the mast cell secretagogue compound 48/80.. Inhibition of mast cell secretion was documented by light and electron microscopy and extended to stimulation by substance P or IgE and antigen.. The inhibition was more potent than that seen with the clinically available mast cell stabilizer disodium cromoglycate (cromolyn). Maximal inhibition by pentosanpolysulfate was apparent within 1 minute, was unaffected by the length of pre-incubation and persisted after the drug was washed off. In contrast, the effect of cromolyn was limited by rapid tachyphylaxis. In addition, while cromolyn has no effect on mucosal or rat basophilic leukemia cells, pentosanpolysulfate inhibited histamine secretion from both. Confocal microscopy using a calcium indicator dye showed that pentosanpolysulfate decreased intracellular calcium ion levels.. Pentosanpolysulfate appears to be a potent inhibitor of allergic and nonimmune mast cell stimulation, which is an alternative explanation of its benefit in interstitial cystitis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcium; Chondroitin Sulfates; Cromolyn Sodium; Cystitis, Interstitial; Dose-Response Relationship, Drug; Histamine Release; Histocytochemistry; Immunoglobulin E; Male; Mast Cells; Microscopy, Confocal; Microscopy, Electron; p-Methoxy-N-methylphenethylamine; Pentosan Sulfuric Polyester; Peritoneum; Rats; Rats, Sprague-Dawley; Substance P; Urinary Bladder

We compared urinary glycosaminoglycan levels in patients with interstitial cystitis and healthy controls.. Total sulfated glycosaminoglycans assayed by dimethylmethylene blue binding and individual glycosaminoglycans analyzed by cellulose acetate electrophoresis were compared in patients with interstitial cystitis and healthy controls. Also, multiple urine samples were obtained from healthy female controls for 2 months to assess the relationship of urinary glycosaminoglycan and creatinine concentrations, and to determine whether glycosaminoglycan excretion changes during the menstrual cycle.. Total sulfated glycosaminoglycan and creatinine concentrations correlated well in random voided samples. Menstrual cycle day did not affect total sulfated glycosaminoglycan levels. Cellulose acetate electrophoresis revealed 3 bands corresponding to chondroitin sulfates, heparan sulfate and acidic glycoprotein. Patients with interstitial cystitis had decreased urinary concentrations of each of these individual components and total sulfated glycosaminoglycans. However, glycosaminoglycan-to-creatinine ratios were similar in interstitial cystitis and control urine.. Using these assays total and individual urinary glycosaminoglycan levels normalized to creatinine were not altered in interstitial cystitis.

Topics: Chondroitin Sulfates; Cystitis, Interstitial; Female; Glycosaminoglycans; Heparin; Humans; Menstrual Cycle

To investigate the abundance of chondroitin sulfate proteoglycans at the bladder lumenal and subepithelial surfaces in bladder biopsies derived from patients with interstitial cystitis (IC) and controls.. Tissue sections derived from biopsies from 31 IC patients and 24 pathologically normal control sections were labeled for proteoglycans using the 2B6 anti-"stub" antibody and detected by immunohistochemistry.. On the lumenal surface, 5 of 31 (19%) IC sections were positive for proteoglycans versus 14 of 24 (58%) control sections (P = 0.00011). At the basal surface, 5 of 19 IC patients were positive versus 7 of 12 controls (P = 0.032).. A deficit of bladder lumenal and basal proteoglycans is associated with IC. The deficit in basal layer proteoglycans suggests an altered urothelial differentiation program. The lumenal deficit suggests that the charge-dependent exclusion of ions from the bladder surface is compromised in IC.

Topics: Chondroitin Sulfates; Cystitis, Interstitial; Epithelium; Humans; Proteoglycans; Urinary Bladder