OBJECTIVES: To investigate the therapeutic efficacy and mechanism of pentosan polysulfate (PPS) for cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) in mice. METHODS: Female C57BL/6 mice (6-8 weeks old) were randomized into control group, PPS treatment (25 mg/kg via gavage for 3 weeks) group, CYP treatment (3 separate intraperitoneal injections at 50 mg/kg in week 4), and CYP+PPS treatment group. Gut microbiota alterations of the mice were analyzed using 16S rDNA sequencing and non-targeted metabolomics. Fecal microbiota transplantation (FMT) was performed in CYP-treated recipient mice and those treated with both CYP and PPS. In the in vitro experiment, LPS-stimulated human bladder epithelial cells (SV-HUC-1) were used to assess the effects of deoxycholic acid (DCA) and TGR5 signaling inhibitor SBI-115 on barrier functions of bladder epithelial cells. RESULTS: PPS treatment significantly improved the mechanical pain thresholds, restored the urodynamic parameters, and attenuated bladder inflammation and barrier dysfunction in CYP-treated mice. Mechanistically, PPS enriched the abundance of Eubacterium xylanophilum and increased DCA levels in the intestines of CYP-treated mice. FMT experiments confirmed microbiota-dependent therapeutic effects of PPS, shown by reduced bladder pathology in the recipient mice treated with both CYP and PPS. In SV-HUC-1 cells, DCA obviously alleviated LPS-induced inflammation and barrier disruption, and treatment with SBI-115 abolished these protective effects of DCA. CONCLUSIONS PPS ameliorates IC/BPS in mice by remodeling gut microbiota to enhance DCA production and activate TGR5 signaling, suggesting a novel microbiota-bile acid-TGR5 axis that mediates the therapeutic effect of PPS and a therapeutic strategy for IC/BPS by targeting gut-bladder crosstalk.
Animals ; Cystitis, Interstitial/drug therapy* ; Gastrointestinal Microbiome/drug effects* ; Pentosan Sulfuric Polyester/therapeutic use* ; Cyclophosphamide/adverse effects* ; Mice, Inbred C57BL ; Female ; Mice ; Bile Acids and Salts/metabolism* ; Urinary Bladder ; Fecal Microbiota Transplantation ; Humans

OBJECTIVE: To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC). METHODS: Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes. RESULTS: A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment (P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group (P < 0.05). CONCLUSION Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.
Humans ; Female ; Cystitis, Interstitial/drug therapy* ; Administration, Intravesical ; Retrospective Studies ; Sodium Bicarbonate/therapeutic use* ; Treatment Outcome ; Lidocaine/therapeutic use* ; Heparin/therapeutic use* ; Electrocoagulation

OBJECTIVE: To establish a model of bladder pain syndrome in SD rats by cyclophosphamide intraperitoneal injection, to evaluate the effectiveness of the model from the urodynamic and histological levels, to lay a zoological foundation for the clinical study of bladder pain syndrome, and to further guide clinical treatment. METHODS: Thirty-two 8-week-old SD rats were randomly divided into 4 groups, including acute test group, acute control group, chronic test group, and chronic control group, with 8 rats in each group. The acute test group received intraperitoneal injection of cyclophosphamide 150 mg/kg immediately after the measurement of urodynamic data on the first day, and urodynamic examination was performed again 2 days later. After that, the rats were sacrificed to obtain bladder tissue. In the chronic test group, after measuring the baseline data of urodynamics on the first day, cyclophosphamide 75 mg/kg was intraperitoneally injected on the first, fourth, and seventh days, and the rats were sacrificed after measuring the urodynamic data again on the eighth day to obtain bladder tissue. The acute control group and the chronic control group were injected with the same amount of normal saline during intraperitoneal injection, and the urodynamic testing time point were consistent with the corresponding test groups. Histopathological changes of the bladder were assessed by HE staining. RESULTS: In each acute and chronic group, there were no intragroup differences in baseline urodynamic levels between the test and control groups. The urodynamic maximum bladder volume was significantly reduced in the acute test group after administration(t=-2.961, P < 0.05), histologically, severe interstitial edema, obvious inflammatory cell infiltration, mucosal edema and submucosal hemorrhage, and partial urothelium were absent could be seen, which were consistent with acute cystitis performance. The urodynamic maximum bladder capacity was significantly reduced in the chronic test group after administration (t=-3.886, P < 0.05), and the bladder compliance was lower than that in the control group, but not significant, the histological manifestations were urothelial exfoliation, interstitial edema, submucosal hemorrhage, infiltration of inflammatory cells such as lymphocytes, and dense vascular distribution. CONCLUSION In the acute test group, a single intraperitoneal injection of cyclophosphamide could induce acute bladder inflammation in the rats. In the chronic test group, repeated injections of cyclophosphamide could induce histological changes in chronic inflammation of chronic bladder pain syndrome in the rats. But the bladder function was not significantly impaired.
Animals ; Cyclophosphamide/therapeutic use* ; Cystitis/pathology* ; Cystitis, Interstitial/drug therapy* ; Disease Models, Animal ; Hemorrhage ; Rats ; Rats, Sprague-Dawley ; Urodynamics

BACKGROUNDPhloroglucinol plays an important role in oxidative stress and inflammatory responses. The effects of phloroglucinol have been proven in various disease models. The aim of the present study was to investigate the efficacy and possible mechanisms of phloroglucinol in the treatment of interstitial cystitis (IC).

METHODSThirty-two female Sprague-Dawley (SD) rats were used in this study. IC was induced by intraperitoneal injection of cyclophosphamide (CYP). Rats were randomly allocated to one of four groups (n = 8 per group): A control group, which was injected with saline (75 mg/kg; i.p.) instead of CYP on days 1, 4, and 7; a chronic IC group, which was injected with CYP (75 mg/kg; i.p.) on days 1, 4, and 7; a high-dose (30 mg/kg) phloroglucinol-treated group; and a low-dose (15 mg/kg) phloroglucinol-treated group. On day 8, the rats in each group underwent cystometrography (CMG), and the bladders were examined for evidence of oxidative stress and inflammation. Statistical analysis was performed by analysis of variance (ANOVA) followed by least square difference multiple comparison post-hoc test.

RESULTSHistological evaluation showed that bladder inflammation in CYP-treated rats was suppressed by phloroglucinol. CMG revealed that the CYP treatment induced overactive bladder in rats that was reversed by phloroglucinol. Up-regulated tumor necrosis factor-α and interleukin-6 expression in the CYP-treated rats were also suppressed in the phloroglucinol treated rats. CYP treatment significantly increased myeloperoxidase activity as well as the decreased activities of catalase of the bladder, which was reversed by treatment with phloroglucinol.

CONCLUSIONSThe application of phloroglucinol suppressed oxidative stress, inflammation, and overactivity in the bladder. This may provide a new treatment strategy for IC.

Animals ; Cyclophosphamide ; toxicity ; Cystitis, Interstitial ; chemically induced ; drug therapy ; Female ; Inflammation ; drug therapy ; Oxidative Stress ; drug effects ; Phloroglucinol ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder ; drug effects ; pathology

OBJECTIVETo investigate the therapeutic effect of pentosan polysulfide sodium (PPS) on chronic non-bacterial prostatitis (CNP) in rats.

METHODSBased on Robinette's method, we established a CNP model in 80 male SD rats, aged 6 months and weighing 315 - 450 g, by castration followed by subcutaneous injection of estradiol at 0.25 mg / (kg x d) for 30 consecutive days. Then we randomly allocated the model rats into a placebo group (n = 40) and a PPS group (n = 40) to receive intragastric administration of normal saline and PPS, respectively. After 8 weeks of treatment, the pathological changes in the rat prostatic tissue were observed by HE staining.

RESULTSVaried degrees of chronic inflammation and inflammatory cell infiltration were seen in the prostatic tissues of both groups of rats before the treatment. The inflammation was significantly improved after the treatment in the PPS group but not in the placebo group.

CONCLUSIONPPS has some therapeutic effect on CNP in the rat, and its mechanism may be associated with the abilities of PPS to repair the damaged glycosaminoglycan layer and inhibit inflammation in the prostate.

Animals ; Chronic Disease ; Cystitis, Interstitial ; drug therapy ; Disease Models, Animal ; Male ; Pentosan Sulfuric Polyester ; therapeutic use ; Prostate ; pathology ; Prostatitis ; drug therapy ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo discuss the diagnosis and treatment interstitial cystitis (IC).

METHODSThe clinical date of 10 cases of IC (all women) were analyzed. Their age ranged from 31 to 63 years, with a mean of 41 years. Their courses ranged from 1.5 to 7 years, with a mean of 3.4 years. The symptom criteria of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) was met for IC and no patients had Hunner's ulcer. Potassium sensitivity tests (PST) were performed in all cases. Eight were positive. The O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) was used as treatment outcome measures. ICSI score was from 9 to 20 (mean, 14 +/- 4) at baseline. All the patients were treated with hydrodistention initially. Efficacy was evaluated at 1 month after hydrodistention. The patients who failed to respond to the treatment and recurrence after the treatment were treated by oral or intravesical therapy.

RESULTSThe 10 cases were followed up for 3 to 26 months (mean, 7.8 months) after hydrodistention. Five patients obtained symptom relief. Among them, symptom significantly relieved or disappeared in 2, with the score decreased > 7; symptom partially relieved in 3, with the score decreased > 3. Five cases failed to respond to the treatment. Two cases had recurrence 3 and 6 months after the treatment. The effective rate was 50%. The ICSI score was decreased to 11 +/- 6 at 1 month (t = 4.394, P < 0.05) after the treatment. Those who failed to respond or recurrence after hydrodistention were treated by other methods. Two case were treated with oral Pentosan Polysulfate, effective. Three cases were treated with amitriptylin, 2 effective. Three cases were treated with intravesical Dimethyl sulfoxide plus heparin plus dexamethasone, all effective.

CONCLUSIONSThe diagnosis of IC should meet the symptom criteria of the NIDDK. PST has significant high positive rate in IC patient, which can be used not only for diagnosis but also for instruction. There are a lot of strategies in the management of patients with IC. Hydrodistention is the first choice.

Adult ; Combined Modality Therapy ; Cystitis, Interstitial ; diagnosis ; therapy ; Dilatation ; methods ; Drug Therapy, Combination ; Female ; Humans ; Middle Aged ; Retrospective Studies