Treatment Of Interstitial Cystitis Research Articles

The NLRP3 Inflammasome Inhibitor Dapansutrile Attenuates Cyclophosphamide-Induced Interstitial Cystitis.

Interstitial cystitis (IC)/bladder pain syndrome (BPS), hereafter referred together as IC, is a clinical syndrome characterized by sterile inflammation in the bladder. While the etiology and pathophysiology of IC remain unclear, it may involve autoimmunity in light of the significant role played by the NLRP3 inflammasome. However, the effect of NLRP3 inhibitors including dapansutrile (Dap) on IC had not been explored previously. Here, we investigated the effect of Dap in the cyclophosphamide (CYP)-induced experimental mouse model of IC, which results in functional and histological alterations confined to the urinary bladder (UB) comparable to that of clinical IC. CYP-induced mice treated with Dap exhibited improved UB pathology and reductions in inflammation scores and the frequency and the number of mast cells and neutrophils, relative to mice that received CYP alone. Dap- and CYP-treated mice also exhibited infiltration of T cells in the spleen and iliac lymph nodes (ILNs) and a concurrent significant decrease (p<0.01) in CXCR3+CD8+ T cells in the UB, induction of systemic and mucosal dendritic cells (DCs), and reduced levels of systemic proinflammatory cytokines, as compared to CYP alone. We also observed decreases in the expression of several signaling pathways regulators, including interleukin-1 beta (IL-1β), NLRP3, caspase-1, nuclear factor kappa B (NF-κB), and inducible nitric oxide synthase (iNOS) in the UB of CYP- and Dap-treated mice, relative to those receiving CYP alone. Taken together, these results suggest that Dap suppresses IC through the reduction of CXCR3+T cells, mast cells, and neutrophils in the UB and induces DCs as a protective measure. The present study identifies the mechanisms underlying the amelioration of IC by the NLRP3 inhibitor Dap and may provide an avenue for a potential therapeutic agent for the treatment of IC.

Platelet-rich plasma: application for interstitial cystitis and erectile dysfunction

Up-to-date, the platelet-rich plasma (PRP) treatment method is actively used in many fields of medicine. In traumatology, PRP is used to treat bone and cartilage defects, ligamentous apparatus. In combustiology for the healing of burns, in surgery ¾ trophic ulcers. There is evidence of the feasibility of using PRP in some dermatological diseases, as well as in dental practice. For urology, the method is new and is just beginning to be studied. The article discusses the methods of treatment of interstitial cystitis (IC) and erectile dysfunction (ED) using PRP. During the review, we relied on existing data on the effectiveness of intravesical injections of PRP in the treatment of IC, as well as on the successful treatment of ED with activated, nonactivated PRP and PRP augmented phosphodiesterasetype 5 (PDE-5) inhibitors.

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

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

Anti-inflammatory iron chelator, DIBI, reduces leukocyte-endothelial adhesion and clinical symptoms of LPS-induced interstitial cystitis in mice.

Interstitial cystitis (IC) is a prevalent and debilitating chronic inflammatory disease of the urinary bladder. Currently there are no fully effective therapeutic agents available, in part due to the still obscure pathogenesis of IC. Lipopolysaccharide (LPS) also known as endotoxin from Gram negative bacteria elicits IC in mice and has formed the basis of model systems for investigation. Excess free iron plays an important role in inflammation through generation of reactive oxygen species (ROS). The novel iron chelator DIBI has been shown to sequester excess free iron and dampen excess inflammatory responses to systemic LPS administration and also to Gram negative bacterial infections. The overall objective of this study was to evaluate the effects of DIBI on LPS induced IC in mice. Leukocyte activation, endothelial adhesion and functional capillary density were assessed by intravital microscopy of the bladder microcirculation following a single intravesical LPS administration with or without intravesical DIBI treatment. Clinical IC symptoms were also assessed through behavioral and pain threshold force measurements. Four groups of female BALB/c mice (n = 5-6/group) were randomized in this study: control group, IC group without therapy, IC group with DIBI therapy and control group with DIBI therapy. The groups were examined using intravital microscopy (IVM) of the bladder for leukocyte-endothelial interactions (adherent leukocytes, temporarily interacting leukocytes) and functional capillary density (FCD). A modified behavioral score by Boucher et al. and Von-Frey-Aesthesiometry were used to evaluate key behavioral indices related to pain and visceral pain perception. LPS introduced intravesically induced an early (≤2h) inflammation of the bladder evidenced by leukocyte activation and adhesion to bladder capillary walls. Intravesical DIBI therapy of mice 30min following LPS administration and assessed after 1.5h treatment showed a significant decrease in the number of adherent leukocytes compared to IC animals without DIBI treatment. DIBI treated mice showed a significantly lowered increase in behavioral distress scores compared to IC mice without therapy. Untreated IC mice exhibited a significantly decreased threshold force value for evoked pain response and DIBI treatment improved the threshold pain response. A significant inverse correlation was found for the two pain and suffering evaluation methods results. DIBI reduced inflammatory endothelial leukocyte adhesion and key indices related to pain and suffering over those observed in untreated IC mice. Our findings suggest a potential therapeutic role for DIBI for IC treatment.

Diagnosis of interstitial cystitis: practice-orientated diagnostic work-up

Interstitial cystitis is a chronic orphan disease of the urinary bladder characterised by its main symptoms of bladder pain, persistent urge to void and urinary frequency. Due to a variety of confusable diseases and different pathophysiologies, the diagnosis of IC is still a diagnosis of exclusion and remains a challenge for doctors and patients alike. Patients often experience misdiagnosis and unsuccessful treatment for years. Therefore, the primary goal for these patients with chronic pain must be a rapid diagnosis and initiation of adequate treatment. This article focuses on transferring the consensus-based recommendations of the current German S2k guideline "Diagnosis and Treatment of Interstitial Cystitis" (IC/BPS) (2018 AWMF register No.: 043/050) into a practice-orientated and structured diagnostic work-up process.

P03 - The potential use of medical grade Manuka honey in the treatment of interstitial cystitis/ bladder pain syndrome

P03 - The potential use of medical grade Manuka honey in the treatment of interstitial cystitis/ bladder pain syndrome

A Novel Use of Cyclobenzaprine and Hyoscyamine (BLAVACARE TM) Impregnated Vaginal Suppositories for the Symptomatic Treatment of Interstitial Cystitis, Bladder Spasms, and Painful Bladder Syndrome

Interstitial Cystitis and Painful Bladder Syndrome are chronic conditions that are associated with urinary frequency, urgency, pain, and nocturia. The etiology of IC/PBS is not clearly understood, therefore diagnosis and treatment can be challenging. IC/PBS greatly affects the quality of life in several ways. In this report, we present the case of a patient with longstanding interstitial cystitis symptoms who was successfully treated with a novel approach after failing treatment established by the current guidelines in the management of IC/PBS. This case illustrates the complex nature of this syndrome and offers a new treatment approach that can potentially change the way IC/PBS are medically managed.

Efficacy and safety of povidone iodine with dimethyl sulfoxide vs 0.05% tretinoin in treatment of molluscum contagiosum: A randomized case control study

Efficacy and safety of povidone iodine with dimethyl sulfoxide vs 0.05% tretinoin in treatment of molluscum contagiosum: A randomized case control study

Differential Expression of microRNAs Correlates With the Severity of Experimental Autoimmune Cystitis.

Interstitial cystitis (IC)/bladder pain syndrome (BPS) primarily affects women. It varies in its severity and currently has no effective treatment. The symptoms of IC include pelvic pain, urgency and frequency of urination, and discomfort or pain in the bladder and lower abdomen. The bladders of IC patients exhibit infiltration by immune cells, which lends credence to the hypothesis that immune mechanisms also play a role in the etiology and pathophysiology of IC. The Differentially expressed microRNAs (miRs) in immune cells may serve as crucial immunoregulators in the IC. Therefore, we sought to determine whether miRs might play a regulatory role in the progression and pathogenesis of IC, using experimental autoimmune cystitis (EAC) model. In the present study, we observed differential expression of a specific subset of miRs in iliac lymph nodes (ILNs) and urinary bladders (UB) of IC mice compared to that in control mice. Microarray analysis of 96 miRs from the bladder and 135 miRs from ILNs allowed us to identify 50 that exhibited at least a 1.5-fold greater difference in expression in EAC mice compared to control mice. Hierarchical cluster analysis of the microarray data was used to search available databases to predict molecular pathways with which the miRs might interact. Four miRs from each organ that exhibited altered expression in EAC mice and that were predicted to have roles in inflammation (miR-146a, -181, -1931, and -5112) were selected for further analysis by reverse transcription-polymerase chain reaction (RT-PCR). All were confirmed to be elevated in EAC mice. Histological inflammatory scores, systemic chemokines, and cytokines expressed by T helper type 1 (Th1) lymphocytes were also elevated in EAC mice as compared to control animals. We hypothesize that the mechanism of EAC induction might involve the modulation of specific miRs that increase local and systemic levels of chemokines and cytokines. The present study identifies novel miRs expressed in UB and ILNs that will allow us to highlight mechanisms of EAC pathogenesis and may provide potential biomarkers and/or serve as the basis of new therapies for the treatment of IC.

Beneficial effect of Bletilla striata extract solution on zymosan-induced interstitial cystitis in rat.

Interstitial cystitis (IC) is a chronic pain syndrome that is characterized by suprapubic pain upon bladder filling. Bletilla striata, a well-known traditional Chinese herb with established efficacy in wound healing and anti-inflammation, was hypothesized to improve the symptoms of IC possibly though forming a physical barrier that could isolate the bladder tissue from irritants. This study was conducted to evaluate the beneficial effects of intravesical treatment with B. striata extract solution (BSES) on visceral pain and bladder function of rats with zymosan-induced IC. Thirty female rats were randomly divided into control group, zymosan-induced cystitis rats treated with normal saline (Z + NS), and zymosan-induced cystitis rats treated with BSES (Z + BSES). All rats underwent evaluation for abdominal withdrawal reflex (AWR) scores to assess visceral hypersensitivity, cystometrography, and electromyogram (EMG) of both external urethral sphincter and bladder detrusor. Data were analyzed by one way analysis of variance. The Z + NS group had an increased visceral hypersensitivity as compared to control group. Rats treated with BSES (Z + BSES group) had decreased AWR scores and amplitude of bladder detrusor-EMG. Besides, BSES treatment improved overactive bladder with significant effects on the extend of micturition interval and increase of storage of urine. Intravesical instillation of BSES can significantly alleviate zymosan-induced visceral hypersensitivity and bladder overactivity associated with IC. This study suggested that intravesical instillation with BSES might be a promising treatment for IC.

Development of a novel treatment for interstitialcystitis using filtered adipose-derived stem cells lysate

Development of a novel treatment for interstitialcystitis using filtered adipose-derived stem cells lysate

Forming a Non-Profit Organization for Patients with a Urological Disease in 1984: Does it relate to Clinical Microbiology Today?

Interstitial Cystitis (IC), also known as Painful Bladder Syndrome (PBS), was initially described in the mid 1800’s. It was not until 1984 that a patient non-profit organization, the Interstitial Cystitis Association (ICA), was formed in order to work with IC patients and the National Institutes of Health (NIH) to define and increase research on this enigmatic and debilitating condition. The media played an important role in bringing together patients and helping them understand that they were not alone in their suffering. Epidemiological studies legitimized the disease and research at the NIH and other academic institutions progressed enormously. However, despite over 30 years of hard work, urologists have been unable to determine a cause for IC or any truly effective treatments to help patients suffering from this condition. Collaboration with other specialties, in particular clinical microbiology, may prove fruitful in advancing research into the cause and potential treatments for IC.

Opioid prescription use in patients with interstitial cystitis.

The opioid epidemic is a recent focus of national initiatives to reduce opioid misuse and related addiction. As interstitial cystitis (IC) is a chronic pain state at risk for narcotic use, we sought to assess opioid prescription use in patients with IC. Data were accessed from the Virginia All Payers Claims Database. We identified female patients diagnosed with IC from 2011 to 2016 using International Classification of Disease codes. A patient identifier was used to link diagnoses with outpatient prescription claims for opioids using generic product identifiers. We then analyzed opioid prescriptions within 30days of a claim with a diagnosis of IC. A total of 6,884 patients with an IC diagnosis were identified. The median number of IC claims per patient was 2 (IQR 1 to 4). Mean patient age was 47.8. Twenty-eight percent of patients received at least 1 opioid prescription, with a median of 2 (IQR 1, 4) per patient. Among those receiving opioids, 185 (9.5%) had more than 10 opioid prescriptions, with a maximum of 129. The most common prescriptions were hydrocodone (n = 2,641, 32.3%), oxycodone (n = 2,545, 31.2%), and tramadol (n = 1,195, 14.6%). There was a decline in opioid prescriptions per month for IC, although the rate per IC diagnosis remained stable. A significant number of patients with IC are treated with opioids. Although the overall number of opioid prescriptions associated with IC had declined, the prescription rate per IC diagnosis had not. As part of the national initiative to reduce opioid use, our data suggest that IC treatment strategies should be examined.

Platelet Enriched Plasma for Treatment of Interstitial Cystitis

Platelet Enriched Plasma for Treatment of Interstitial Cystitis

Adverse reactions of dimethyl sulfoxide in humans: a systematic review.

Background: Dimethyl sulfoxide (DMSO) has been used for medical treatment and as a pharmacological agent in humans since the 1960s. Today, DMSO is used mostly for cryopreservation of stem cells, treatment of interstitial cystitis, and as a penetrating vehicle for various drugs. Many adverse reactions have been described in relation to the use of DMSO, but to our knowledge, no overview of the existing literature has been made. Our aim was to conduct a systematic review describing the adverse reactions observed in humans in relation to the use of DMSO. Methods: This systematic review was reported according to the PRISMA-harms (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines. The primary outcome was any adverse reactions occurring in humans in relation to the use of DMSO. We included all original studies that reported adverse events due to the administration of DMSO, and that had a population of five or more. Results: We included a total of 109 studies. Gastrointestinal and skin reactions were the commonest reported adverse reactions to DMSO. Most reactions were transient without need for intervention. A relationship between the dose of DMSO given and the occurrence of adverse reactions was seen. Conclusions: DMSO may cause a variety of adverse reactions that are mostly transient and mild. The dose of DMSO plays an important role in the occurrence of adverse reactions. DMSO seems to be safe to use in small doses. Registration: PROSPERO CRD42018096117.

Factors affecting the symptom-free period after hydrodistention in females with interstitial cystitis and painful bladder syndrome

Hydrodistention is one of the effective procedures for the diagnosis as well as treatment of interstitial cystitis and painful bladder syndrome and interstitial cystitis/painful bladder syndrome (IC/PBS). The present study was aimed to investigate the factors affecting the symptom-free period after hydrodistention in females with IC/PBS. In the present study, 32 IC/PBS females with symptom recurrence after hydrodistention who needed further management were included. Clinical information including age, duration suffered from the disease, preoperative functional bladder capacity (FBC), and the distended bladder volume during hydrodistention was investigated. Also, the symptom-free period after hydrodistention and the volume difference between preoperative FBC and distended bladder volume during the hydrodistention (ΔBV) was calculated for the analysis. As the result, ΔBV was the only factor that significantly elongated the symptom-free period after hydrodistention (p < 0.001). Thus, the larger volume difference between preoperative FBC and distended bladder volume during the first hydrodistention elongated the symptom-free period of IC/PBS females after receiving hydrodistention.

Extracorporeal shockwave against inflammation mediated by GPR120 receptor in cyclophosphamide-induced rat cystitis model

BackgroundWe tested the hypothesis that extracorporeal shockwave treatment (ESWT) can abolish inflammation and restore urothelial barrier integrity in acute interstitial cystitis by upregulating the fatty acid receptor GPR120.MethodsA total of 30 female Sprague-Dawley rats were categorized into five groups: (1) sham-operated rats (SC); (2) rats treated with ESWT (SC + ESWT); (3) rats with bladder irritation using 150 mg/kg cyclophosphamide through intraperitoneal injection; (4) cyclophosphamide rats treated with ESWT (cyclophosphamide+ESWT); (5) cyclophosphamide rats treated with GPR120 agonist (cyclophosphamide+GW9508).ResultsOn Day 3, urine and bladder specimens were collected for biochemical, histopathological, immunological, and immunoblotting analysis. Following stimulation with cyclophosphamide, the inhibition of the elevated levels of TAK1/NF-κB and phospho-TAK1/NF-κB by ESWT and GPR120 agonists in RT4 cells was associated with a suppression of NF-κB translocation from the cytosol to the nucleus. Accordingly, this anti-inflammatory effect was abolished by GPR120 antagonist and knockdown of GPR120. Histologically, bladder inflammation in cyclophosphamide-treated rats was suppressed by GW9508 or ESWT. Masson’s trichrome and Sirius red staining revealed that cyclophosphamide treatment enhanced synthesis of extracellular matrix in rats that was reversed by GW9508 or ESWT. Upregulated pro-inflammatory mediators and cytokines in the cyclophosphamide-treated rats were also suppressed in the GW9508- or ESWT-treated rats. The significantly increased inflammatory cell infiltration as well as the impaired urothelial integrity of the bladder after cyclophosphamide treatment were reversed by treatment with GW9508 or ESWT.ConclusionsThese findings suggest that GPR120, the sensing receptor for ESWT, may be useful in the treatment of interstitial cystitis by inhibiting inflammatory response in bladder cells.

Adverse reactions of dimethyl sulfoxide in humans: a systematic review

Background: Dimethyl sulfoxide (DMSO) has been used for medical treatment and as a pharmacological agent in humans since the 1960s. Today, DMSO is used mostly for cryopreservation of stem cells, treatment of interstitial cystitis, and as a penetrating vehicle for various drugs. Many adverse reactions have been described in relation to the use of DMSO, but to our knowledge, no overview of the existing literature has been made. Our aim was to conduct a systematic review describing the adverse reactions observed in humans in relation to the use of DMSO. Methods: This systematic review was reported according to the PRISMA-harms (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines. The primary outcome was any adverse reactions occurring in humans in relation to the use of DMSO. We included all original studies that reported adverse events due to the administration of DMSO, and that had a population of five or more. Results: We included a total of 109 studies. Gastrointestinal and skin reactions were the commonest reported adverse reactions to DMSO. Most reactions were transient without need for intervention. A relationship between the dose of DMSO given and the occurrence of adverse reactions was seen. Conclusions: DMSO may cause a variety of adverse reactions that are mostly transient and mild. The dose of DMSO plays an important role in the occurrence of adverse reactions. DMSO seems to be safe to use in small doses. Registration: PROSPERO CRD42018096117.

Assessment of treatment outcomes of interstitial cystitis with hydrodistention and bladder training by O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices

ObjectiveTo investigate whether the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) is efficacy measure tool for interstitial Cystitis (IC) treatment with hydrodistention (HD) and bladder training (BT). Materials and methodsFrom January 2003 to March 2006, 108 consecutive IC patients were treated by HD and BT after HD. This study evaluated the efficacy of treatment with the specific questionnaire for IC, the ICSI and ICPI. Each patient filled out the questionnaire before HD and three months after HD and BT. The efficacy of the treatment was evaluated using the average scores of ICSI and ICPI. ResultsThe mean ± margin of error, (95% confidence interval) of total scores of ICSI and ICPI were 13.89 ± 2.95, (13.33–14.45) and 12.51 ± 2.50, (12.04–12.98) before HD, respectively, and were 2.70 ± 1.16, (2.44–2.95) and 1.99 ± 1.27, (1.71–2.26) (all p < 0.005) three months after HD and BT, respectively. ConclusionO'Leary-Sant ICSI and ICPI is not only a screening tool for IC but also a useful assessment tool for IC treatment outcomes.

An epigenetic switch on ARID1A chromatin remodeler by alpha‐oxoglutarate activates the antiproliferative axis in interstitial cystitis

Interstitial cystitis (IC) is a chronic urinary tract disease that is characterized by unpleasant sensations, such as chronic pelvic pain and various other symptoms, in the absence of infection or other identifiable causes. We previously performed comprehensive metabolomics profiling of urine in IC patients using nuclear magnetic resonance and gas-chromatography/mass spectrometry and found that urinary α-oxoglutarate was significantly elevated. α-oxoglutarate (α-OG), the tricarboxylic acid (TCA) cycle intermediate, reportedly functions to suppress the proliferation of normal human bladder epithelial cells. Here, we identified AT-rich interactive domain 1A (ARID1A), a key chromatin remodeler, as being hypomethylated and upregulated by 2-oxoglutarate treatment. This was done through EPIC DNA methylation profiling and subsequent biochemical approaches, including quantitative RT-PCR and western blot analyses. Furthermore, we found that α-oxoglutarate almost completely suppresses ten-eleven translation (TET) activity, but does not affect DNA methyltransferase (DNMT) activity. DNMT inhibition in our IC rat models did not limit IC-associated symptoms or cytokine production. Altogether, our studies reveal the potential role of α-OG in epigenetic remodeling through its effects on AR1DA and TET in the bladder, which could provide a promising therapeutic strategy for IC treatment. Support or Funding Information The authors acknowledge support from National Institutes of Health grants (1U01DK103260, 1R01DK100974, U24 DK097154, NIH NCATS UCLA CTSI UL1TR000124), Department of Defense grants (W81XWH-15-1-0415), Centers for Disease Controls and Prevention (1U01DP006079), IMAGINE NO IC Research Grant, the Steven Spielberg Discovery Fund in Prostate Cancer Research Career Development Award, the U.S.-Egypt Science and Technology Development Fund by the National Academies of Sciences, Engineering, and Medicine (to J.K.). J.K. is former recipient of Interstitial Cystitis Association Pilot Grant, a Fishbein Family IC Research Grant, New York Academy of Medicine, and Boston Children's Hospital Faculty Development. The funders had no role in the design, data collection and analysis, decision to publish or preparation of the manuscript. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.