Innate Bacteriostatic Mechanisms Defend the Urinary Tract.

Urinary tract infection (UTI) is the most common type of urogenital disease. UTI affects the urethra, bladder, ureter, and kidney. A total of 13.3% of women, 2.3% of men, and 3.4% of children in the United States will require treatment for UTI. Traditionally, bladder (cystitis) and kidney (pyelonephritis) infections are considered independently. However, both infections induce host defenses that are either shared or coordinated across the urinary tract. Here, we review the chemical and biophysical mechanisms of bacteriostasis, which limit the duration and severity of the illness. Urinary bacteria attempt to overcome each of these defenses, complicating description of the natural history of UTI.

EBV infection mediated BDNF expression is associated with bladder inflammation in interstitial cystitis/bladder pain syndrome with Hunner's lesion.

Interstitial cystitis/bladder pain syndrome with Hunner's lesion (HIC) is characterized by chronic inflammation and nerve hyperplasia; however, the pathogenesis of HIC remains a mystery. In this study, we detected both Epstein-Barr virus (EBV) latency infection genes EBNA-1 and LMP-1 and EBV lytic infection BZLF-1 and BRLF-1 expression in the HIC bladders, indicating the coexistence of EBV persistence and reactivation in the B cells in HIC bladders. Upregulation of EBV-associated inflammatory genes in HIC bladders, such as TNF-α and IL-6, suggests EBV infection is implicated in the pathogenesis of bladder inflammation. Nerve hyperplasia and upregulation of brain-derived neurotrophic factor (BDNF) were noted in the HIC bladders. Double immunochemical staining and flow cytometry revealed the origin of BDNF to be EBV-infected B cells. Inducible BDNF expression was noted in B cells upon EBV infection, but not in the T cells. A chromatin immunoprecipitation study revealed BDNF transcription could be promoted by cooperation between EBV nuclear antigens, chromatin modifiers, and B-cell-specific transcription. Knockdown of BDNF in EBV-infected B cells resulted in the inhibition of cell proliferation and viability. Downregulation of phosphorylated SMAD2 and STAT3 after BDNF knockdown may play a role in the mechanism. Implantation of latent EBV-infected B cells into rat bladder walls resulted in a higher expression level of CD45 and PGP9.5, suggesting tissue inflammation and nerve hyperplasia. In contrast, implantation of BDNF depleted EBV-infected B cells abrogated these effects. This is the first study to provide insights into the mechanisms underlying the involvement of EBV-infected B cells in HIC pathogenesis. © 2022 The Pathological Society of Great Britain and Ireland.

The effects of a galectin-3 inhibitor on bladder pain syndrome in mice with cyclophosphamide-induced cystitis.

AIMS: To explore the effect of blocking galectin-3 in the bladder pain syndrome associated with interstitial cystitis. METHODS: A galectin-3 inhibitor was used to treat mice with cyclophosphamide-induced cystitis. The expression of galectin-3 in bladder tissues and urine was examined by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. Suprapubic-pelvic pain, bladder voiding, bladder pain-like nociceptive behavior, and referred hyperalgesia were assessed. The weights of the bladders were also measured, and inflammatory cell infiltration and inflammatory cytokine levels were examined by histopathological evaluation. The inflammatory cytokines interleukin 1ß (IL-1ß), nerve growth factor (NGF), IL-6, and tumor necrosis factor α (TNF-α) were measured by ELISA. RESULTS: Increases in galectin-3 levels, inflammation, bladder weight, and bladder pain-related symptoms were observed in bladders with cyclophosphamide-induced cystitis. Administration of the galectin-3 inhibitor significantly mitigated bladder pain-related symptoms and inflammatory response. In response to the 500 µM dose of the galectin-3 inhibitor, nociceptive behaviors, nociceptive score, and bladder-to-body weight ratios were reduced by 65.1%, 65.3%, and 40.3%, respectively, while 500 µM Gal-3 inhibitor increased pelvic pain threshold by 86.7%. Moreover, galectin-3 inhibitor treatment inhibited the inflammation. Compared to untreated CYP-induced mice, there were significant changes in the levels of IL-1ß (41.72 ± 2.05 vs. 18.91 ± 2.26 pg/mg tissues), NGF (9.64 ± 0.38 vs. 1.88 ± 0.05 pg/mg tissues), IL-6 (42.67 + 1.51 vs. 21.26 + 2.78 pg/mg tissues, and TNF-α (22.02 ± 1.08 vs. 10.70 ± 0.80 pg/mg tissues) in response to the highest dose of the Gal-3 inhibitor subgroup (500 µM), and 500 µM Gal-3 inhibitor reduced mast cell infiltration ratios by 71.8%. CONCLUSIONS: The galectin-3 inhibitor relieved pelvic pain, urinary symptoms, and bladder inflammation in mice with cyclophosphamide-induced cystitis. Thus, galectin-3 inhibitors may be novel agents in interstitial cystitis treatment.

Ketamine cystitis following ketamine therapy for treatment-resistant depression - case report.

BACKGROUND: Ketamine is a novel and exciting putative antidepressant medication for patients with treatment-resistant depression. A complication commonly seen in frequent and heavy recreational use of ketamine is ulcerative cystitis, which presents with lower urinary tract symptoms (LUTS) and upper renal tract damage and can be seen in over 25% of regular users. Although Ketamine-induced cystitis (KIC) is a recognised complication in recreational use of ketamine, its occurrence in therapeutic use of ketamine in depression has so far not been reported. The exact pathogenesis of KIC is currently unknown, making treatment and prevention advice much more difficult. Early diagnosis of KIC and immediate cessation of ketamine has been shown to improve adverse urinary tract symptoms and prevent further damage. CASE PRESENTATION: We present a case of a 28-year-old female who was started on ketamine treatment for depression, and who then developed symptoms of KIC, which was confirmed by urine microscopy, culture and analysis. CONCLUSIONS: To our knowledge, this is the first reported case of KIC in a patient receiving treatment-dose ketamine as part of their antidepressant therapy.

Cystitis glandularis with concomitant Crohn's disease leading to a paroxysm of Crohn's disease with ulcerated external iliac vessels.

•we report the case of a 36-year-old female patient who presented to our hospital with a diagnosis of cystitis glandularis manifesting as a vesicovaginal fistula. She underwent cystoscopic biopsy at a local hospital, but anti-inflammatory treatment was ineffective, and the patient was experiencing low urination frequency and urgency, as well as pain. The patient underwent laparoscopic repair of a cystoscopy-confirmed vesicovaginal fistula. After surgery, the patient experienced a paroxysm of Crohn's disease with multiple small bowel fistulas and erosion of the external iliac vessels that ruptured to form an external iliac vessel small bowel fistula. The fistula was confirmed by surgical exploration, and the patient eventually died.

Bladder Mucosal Cystitis Cystica Lesions Are Tertiary Lymphoid Tissues That Correlate With Recurrent Urinary Tract Infection Frequency in Postmenopausal Women.

PURPOSE: We identify correlates and clinical outcomes of cystitis cystica, a poorly understood chronic inflammatory bladder change, in women with recurrent urinary tract infections. MATERIALS AND METHODS: A retrospective, observational cohort of women with recurrent urinary tract infections who underwent cystoscopy (n=138) from 2015 to 2018 were identified using electronic medical records. Cystitis cystica status was abstracted from cystoscopy reports and correlations were identified by logistic regression. Urinary tract infection-free survival time associated with cystitis cystica was evaluated by Cox proportional hazards regression. Exact logistic regression was used to identify factors associated with changes to cystitis cystica lesions on repeat cystoscopy. Biopsies of cystitis cystica lesions were examined by routine histology and immunofluorescence. RESULTS: Fifty-three patients (38%) had cystitis cystica on cystoscopy. Cystitis cystica was associated with postmenopausal status (OR: 5.53, 95% CI: 1.39-37.21), pelvic floor myofascial pain (6.82, 1.78-45.04), having ≥4 urinary tract infections in the past year (2.28, 1.04-5.09), and a shorter time to next urinary tract infection (HR: 1.54, 95% CI: 1.01-2.35). Forty-two patients (82%) demonstrated improvement or resolution of lesions. Ten/11 (91%) biopsied cystitis cystica lesions were tertiary lymphoid tissue with germinal centers and resembled follicular cystitis. CONCLUSIONS: Cystitis cystica lesions were associated with postmenopausal status, pelvic floor myofascial pain, and number of urinary tract infections in the prior year and predicted worse recurrent urinary tract infection outcomes. Cystitis cystica lesions are tertiary lymphoid tissue/follicular cystitis that may improve or resolve over time with treatment. Identifying cystitis cystica in recurrent urinary tract infection patients may be useful in informing future urinary tract infection risk and tailoring appropriate treatment strategies.

Why Are Some People with Lower Urinary Tract Symptoms (LUTS) Depressed? New Evidence That Peripheral Inflammation in the Bladder Causes Central Inflammation and Mood Disorders.

Anecdotal evidence has long suggested that patients with lower urinary tract symptoms (LUTS) develop mood disorders, such as depression and anxiety, at a higher rate than the general population and recent prospective studies have confirmed this link. Breakthroughs in our understanding of the diseases underlying LUTS have shown that many have a substantial inflammatory component and great strides have been made recently in our understanding of how this inflammation is triggered. Meanwhile, studies on mood disorders have found that many are associated with central neuroinflammation, most notably in the hippocampus. Excitingly, work on other diseases characterized by peripheral inflammation has shown that they can trigger central neuroinflammation and mood disorders. In this review, we discuss the current evidence tying LUTS to mood disorders, its possible bidirectionally, and inflammation as a common mechanism. We also review modern theories of inflammation and depression. Finally, we discuss exciting new animal studies that directly tie two bladder conditions characterized by extensive bladder inflammation (cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction) to neuroinflammation and depression. We conclude with a discussion of possible mechanisms by which peripheral inflammation is translated into central neuroinflammation with the resulting psychiatric concerns.

[The effect of a medicinal plant preparation on the frequency of episodes of exacerbation of recurrent cystitis and metabolic parameters in patients with type 2 diabetes mellitus taking glyphlosins].

BACKGROUND: The problem of recurrent urinary tract infections (UTI) in patients with type 2 diabetes mellitus (DM 2) is relevant, especially when there is a combination of predisposing factors, such as female gender, history of UTI episodes, and therapy with sodium glucose cotransporter type 2 (SGLT-2) inhibitors, and the choice of effective and safe means could cause some difficulties, including ina terms of the burden of antibiotic resistance. AIM: To evaluate the effectiveness and safety of the phytoproduct Canephron® N for the prevention of exacerbations of recurrent cystitis and the effect on metabolic parameters in patients with type 2 diabetes taking SGLT-2 inhibitors. MATERIALS AND METHODS: Prospective, randomized, open, parallel group study in 60 women. The main group took the drug Canephron® N for 3 months. The main parameters for evaluating were the frequency of recurrence of cystitis, level of albuminuria and LDL-cholesterol peroxidation product - malondialdehyde. RESULTS: Within 3 months of taking Canephron® N, exacerbations of chronic cystitis were diagnosed 2 times less often, a decrease in albuminuria was found in the form of an increase in the proportion of patients with an optimal level of albuminuria by 20%, a 50% reduction in the frequency of the initial increase in albuminuria, and the absence of moderate albuminuria in all patients at the end of course of therapy. A decrease in the level of MDA by 1.4 times was noted (p=0.019). CONCLUSION: Thus, the herbal drug Canephron® N can be used for accompanying therapy and prophylactic treatment in patients with recurrent cystitis on the background of DM 2, taking SGLT-2 inhibitors. The course of therapy should last at least 3 months.

Absence of prostacyclin greatly relieves cyclophosphamide-induced cystitis and bladder pain in mice.

Cyclophosphamide (CP) has been widely used in the treatment of various malignancies and autoimmune diseases, but acrolein, a byproduct of CP, causes severe hemorrhagic cystitis as the major side effect of CP. On the other hand, a large amount of prostacyclin (PGI2 ) is produced in bladder tissues, and PGI2 has been shown to play a critical role in bladder homeostasis. PGI2 is biosynthesized from prostaglandin (PG) H2 , the common precursor of PGs, by PGI2 synthase (PTGIS) and is known to also be involved in inflammatory responses. However, little is known about the roles of PTGIS-derived PGI2 in bladder inflammation including CP-induced hemorrhagic cystitis. Using both genetic and pharmacological approaches, we here revealed that PTGIS-derived PGI2 -IP (PGI2 receptor) signaling exacerbated CP-induced bladder inflammatory reactions. Ptgis deficiency attenuated CP-induced vascular permeability and chemokine-mediated neutrophil migration into bladder tissues and then suppressed hemorrhagic cystitis. Treatment with RO1138452, an IP selective antagonist, also suppressed CP-induced cystitis. We further found that cystitis-related nociceptive behavior was also relieved in both Ptgis-/- mice and RO1138452-treated mice. Our findings may provide new drug targets for bladder inflammation and inflammatory pain in CP-induced hemorrhagic cystitis.

Emphysematous cystitis as a potential marker of severe Crohn's disease.

BACKGROUND: Emphysematous cystitis (EC) is characterized by the presence of air within the bladder wall, often a complication of urinary tract infection (UTI) by gas-producing organisms. However, EC has also been reported in the setting of infectious colitis suggesting an alternate etiology. We report a rare case of EC in the setting of severe Crohn's colitis with no clinical evidence of UTI. CASE PRESENTATION: A 43-year old female presented with a 2-month history of bloody diarrhea consisting of 8-12 bowel movements a day, weight loss of 10 kg and peripheral edema. She also had multiple ulcerated lesions on her abdominal wall and in the perianal region. Initial CT scan was significant for pancolitis, anasarca and EC. The follow-up CT cystogram, flexible cystoscopy and pelvic MRI confirmed the diagnosis of EC and ruled out any fistulous tracts in the pelvis including enterovesical/colovesical fistula. The patient did not report any urinary symptoms and the urinalysis was within normal limits. An extensive infectious workup was negative. Despite the paucity of infectious findings, the EC was empirically treated with an intravenous third-generation cephalosporin. Colonoscopy was significant for multiple ulcerated and hyperemic areas with pseudopolyps all throughout the right, transverse and left colon. Biopsies confirmed Crohn's colitis with no evidence of granulomata or dysplasia. Immunohistochemistry was negative for CMV. The perianal and abdominal wall lesions were suspected to be pyoderma gangrenosum although biopsies were equivocal. The colitis was initially treated with intravenous steroids followed by biologic therapy with Infliximab. Despite appropriate escalation of therapies, the patient developed colonic perforation requiring subtotal colectomy. CONCLUSION: This is a rare case of EC in a patient with severe Crohn's colitis. There was no evidence of urinary tract infection or fistulising disease. According to our review, this is the first reported incident of EC in a patient with inflammatory bowel disease without any prior intra-abdominal surgeries. While active Crohn's disease alone is a critical illness, we conclude that concomitant EC may be a poor prognostic factor.

Eosinophilic cystitis complicated with cystitis glandularis: a case report.

BACKGROUND: Eosinophilic cystitis (EC) is a rare inflammatory disease characterized by the gathering and infiltration of numerous eosinophilia (EOS) in the bladder wall. Because of Few cases of EC have been reported globally, the epidemiology of EC is not well known. We report herein the details of one very scarce case of large tumor-like eosinophilic cystitis complicated with cystitis glandularis (CG) diagnosed by biopsy. CASE PRESENTATION: A 45-year-old Chinese man was referred to our hospital for the treatment of right lumbago and odynuria. Ultrasound examination indicated the low echo on the right portion wall and the neck of the bladder. Computed tomography showed a remarkable enhancing large mass that measured 5.0 cm × 2.3 cm located on the right portion of the bladder with undefined margin. For further treatment, diagnostic transurethral resection of the bladder was performed, the postoperative histopathological diagnosis was EC complicated with CG. After transurethral resection, antibiotics, glucocorticoids, and antihistamines were treated. The patient recovered uneventfully and was discharged on postoperative day 8 without evidence of recurrence followed-up for 6 months. CONCLUSION: Large tumor-like eosinophilic cystitis complicated with cystitis glandularis is rare, malignant tumors need to be ruled out. We deem that prompt biopsy led to the exact diagnosis, appropriate treatment led to better prognosis.

Acute unilateral hydronephrosis in the setting of hemorrhagic cystitis.

Acute flank pain associated with hematuria and unilateral hydronephrosis is a classic presentation for an obstructing ureteral stone. However, in the setting of hemorrhagic cystitis, blood can acutely obstruct the distal ureter and infrequently result in hydronephrosis. We present a case of an adult female patient with hemorrhagic cystitis who presented with acute right flank pain associated with unilateral hydronephrosis and perinephric fluid on point-of-care ultrasound (PoCUS) in the absence of renal or ureteral abnormality on CT scan hours earlier. Her symptoms resolved, urine cultures showed no growth, and her outpatient follow-up was unremarkable. We suspect given the acute onset of right obstructive uropathy, an unremarkable CT just hours earlier, and the brief nature of her symptoms, that blood obstructed her distal UVJ leading to acute and transient obstructive uropathy.

Concurrent urachal abscess and florid cystitis glandularis masquerading as malignancy: a case report and literature review.

BACKGROUND: The urachus is the embryological remnant of the cloaca and allantois. Failure of its regression can cause diseases any time after birth. It is difficult to differentiate an abscess from urachal adenocarcinoma based on the clinical presentation and image findings. Cystitis glandularis reflects chronic irritation of the bladder urothelium, and tumor-like florid cystitis glandularis can be misdiagnosed as malignancy. We report a patient with concurrent urachal abscess and florid cystitis glandularis which increased the resemblance of malignancy. CASE PRESENTATION: A 57-year-old female was incidentally found to have a heterogeneous pelvic mass abutting the urinary bladder. A cystoscopy examination revealed protruding tumors located in the bladder dome. Her blood test results were all normal, and urinalysis showed microscopic hematuria. Urachal cancer was diagnosed and en bloc excision of the umbilicus, tumor, and the involved bladder dome was performed. Pathology revealed urachal abscess with concurrent cystitis glandularis within the urinary bladder. No malignancy was identified in the resected specimen. CONCLUSIONS: It is challenging to distinguish urachal abscess from a malignant tumor based on the clinical presentation and imaging studies. As in our case, the coexistence of urachal abscess and tumor-like florid cystitis glandularis increased the resemblance to a malignancy. This is the first reported case of the concurrence of these two disease entities, and emphasizes that the detection of bladder tumors on cystoscopy is not sufficient to make the diagnosis of urachal cancer with bladder involvement.

Improved management of cystitis in primary care following the implementation of a simple multifaceted intervention.

OBJECTIVE: We assessed the impact of the implementation of a simple multifaceted intervention aimed at improving management of cystitis in primary care. DESIGN: Quality control before and after study. SITE: Primary care centres in Barcelona city provided by the Catalonian Institute of Health. PARTICIPANTS: The multifaceted intervention consisted of (1) creation of a group with a leader in each of the primary care centres, out of hours services, sexual and reproductive centres, and home visit service, (2) session on management of cystitis in each centre, (3) result feedback for professionals, and (4) provision of infographics for professionals and patients with urinary tract infections. Interventions started in November 2020 and ended in the summer of 2021. MAIN MEASUREMENTS: Variation in the prescription of first-line antibiotics, usage of antibiotics, and request for urine cultures before and after this intervention. RESULTS: Training sessions took place in 93% of the centres. The use of first-line therapies cystitis increased by 6.4% after the intervention (95% confidence interval [CI], 5.7-7.1%). The use of nitrofurantoin in recurrent cystitis increased, mainly in out of hours service (8.7%; 95% CI, 5.2-12.2%). Urine cultures were more frequently requested after the intervention for recurrent cystitis in both primary care centres and out of hours services, with a 7.2% increase [95% CI, 5.9-8.5%), but also for uncomplicated urinary tract infections (3.1%; 95% CI, 1.8-4.4%). CONCLUSIONS: A low-intensity multifaceted intervention on management of cystitis, with strong institutional support, resulted in a better choice of antibiotic in antibiotic prescribing, but the intervention had less impact on the adequacy of urine cultures.

Complicated urinary tract infection caused by Corynebacterium urealyticum - A pathogen that should not be forgotten.

Although Corynebacterium urealyticum has rarely been isolated in diagnostic laboratories, this bacterium can be a significant uropathogen causing significant complications. It causes cystitis and alkaline encrusted cystitis, commonly involved in patients who need prolonged hospitalization and bladder catheterisation. We report here a case of a 19-yearold young man who was diagnosed with N-Methyl Daspartate receptor (NMDAR) encephalitis that requires hospitalization for optimization of rehabilitation treatment in Hospital Kuala Lumpur, Malaysia. His urine culture isolated slow growing gram-positive pleomorphic rods subsequently identified as C. urealyticum. Based on the risk factors, the isolation of C. urealyticum could not be simply dismissed as contaminants. The patient was treated successfully with vancomycin for two weeks.

[A Case of Panperitonitis Due to Bladder Rupture Caused by Spinal Metastasis of Colorectal Cancer].

A 74-year-old patient was undergoing treatment for ascending colon cancer (cT4aN2M1a) in the Department of Surgery at our hospital. During treatment for increased lymph node metastasis and spinal metastasis, she complained of numbness in her dorsal thigh. Magnetic resonance imaging showed spinal canal stenosis due to L4 bone metastasis. Immediately after starting radiation therapy for L4 bone metastasis, bladder rupture occurred and led to generalized peritonitis. We performed emergency laparotomy and drainage. Later, the patient's general condition improved, but irreversible neurological symptoms remained, and activities of daily living decreased markedly. This was thought to be caused by weakening of the bladder wall due to chronic cystitis, and hyperextension of the bladder due to neurogenic bladder. Bacteriuria leaked into the abdominal cavity, resulting in generalized peritonitis.

Evaluation of hymenal adhesions resection in the treatment of recurrent post-coital cystitis.

OBJECTIVE: To describe and evaluate the technique of hymenal adhesions resection in the treatment of recurrent post-coital cystitis. MATERIALS AND METHODS: Monocentric retrospective observational study including patients operated for hymenal adhesions resection between 2013 and 2020. The indication was based on the association of 4 conditions: at least 3 episodes of documented cystitis per year, a post-coital rhythm, a failure of preventing hygienic and dietary rules, a negative etiological assessment except for the existence of hymenal adhesions. RESULTS: Twenty-three patients were included. The procedures were performed on an outpatient basis. With a mean follow-up of 36.5 months (standard deviation: 22.3), 21 patients (91%) reported a correction of recurrent post-coital cystitis, 16 (70%) had 1 to 2 annual episodes of cystitis, 19 (83%) reported improvement with surgery and satisfaction was rated on average at 8.5/10 (standard deviation: 2.15). None of the 23 patients had persistent documented recurrent cystitis after surgery, 12 (52%) had 1 to 2 documented episodes annually, and 11 (48%) had no documented recurrence. Three cases of postoperative complications were observed: vulvovaginitis, delayed healing, and pyelonephritis. No cases of dyspareunia were reported during the follow-up. CONCLUSION: In case of post-coital cystitis, accompanied by hymenal adhesions, and without any other identified cause, the removal of hymenal adhesions could be an alternative to iterative antibiotic therapy.

Urinary tract infections in children.

Urinary tract infections (UTIs) in children are among the most common bacterial infections in childhood. They are equally common in boys and girls during the first year of life and become more common in girls after the first year of life. Dividing UTIs into three categories; febrile upper UTI (acute pyelonephritis), lower UTI (cystitis), and asymptomatic bacteriuria, is useful for numerous reasons, mainly because it helps to understand the pathophysiology of the infection. A single episode of febrile UTI is often caused by a virulent Escherichia coli strain, whereas recurrent infections and asymptomatic bacteriuria commonly result from urinary tract malformations or bladder disturbances. Treatment of an upper UTI needs to be broad and last for 10 days, a lower UTI only needs to be treated for 3 days, often with a narrow-spectrum antibiotic, and asymptomatic bacteriuria is best left untreated. Investigations of atypical and recurrent episodes of febrile UTI should focus on urinary tract abnormalities, whereas in cases of cystitis and asymptomatic bacteriuria the focus should be on bladder function.

Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR-4/NF-κB, and JAK1/STAT3 signaling in cyclophosphamide-intoxicated rats.

Hemorrhagic cystitis is a potentially deadly complication associated with radiation therapy and chemotherapy. This study explored the protective effect of edaravone (ED) on cyclophosphamide (CP)-induced hemorrhagic cystitis, oxidative stress, and inflammation in rats. The animals received 20 mg/kg ED for 10 days and a single injection of 200 mg/kg CP on day 7. CP induced tissue injury manifested by the diffuse necrotic changes, disorganization of lining mucosa, focal hemorrhagic patches, mucosal/submucosal inflammatory cells infiltrates, and edema. CP increased malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha, and interleukin 6 (IL-6), decreased IL-10, and upregulated toll-like receptor 4 (TLR-4), nuclear factor-kappa B (NF-κB) p65, Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) in the urinary bladder of rats. ED effectively prevented the histopathological alterations, decreased MDA, NO, and inflammatory mediators, and downregulated TLR-4, NF-κB, JAK1, and STAT3 in CP-induced rats. Treatment with ED upregulated ikß kinase ß, IL-10, nuclear factor-erythroid 2 related factor 2 (Nrf2), and cytoglobin, and boosted glutathione, superoxide dismutase, and glutathione S-transferase. Molecular docking simulations revealed the ability of ED to bind TLR-4, NF-κB, JAK1, and STAT3. In vitro, ED increased the cytotoxic activity of CP against HeLa, Caco-2, and K562 cell lines. In conclusion, ED prevented CP-induced hemorrhagic cystitis in rats by attenuating oxidative stress, suppressing TLR-4/NF-κB, and JAK1/STAT3 signaling and boosted Nrf2, cytoglobin, and antioxidants.

A rare case of eosinophilic cystitis involving the inside and outside of the urinary bladder associated with an infected urachal cyst.

BACKGROUND: Eosinophilic cystitis is a rare inflammatory disease of the bladder characterized by eosinophilic infiltration of the bladder wall. Most Eosinophilic cystitis cases present with mucosal lesions of the urinary bladder. We present a very rare case of large mass-forming eosinophilic cystitis, involving the inside and outside of the bladder associated with an infected urachal cyst. CASE PRESENTATION: A 59-year-old man presented with gross hematuria, fever, dysuria, and suprapubic pain. Computed tomography showed a heterogeneously enhancing mass that measured 7.6 cm × 4 cm located on the anterosuperior portion of the bladder with an internal fluid collection. Cystoscopy revealed a raspberry-like mass lesion on the bladder dome. Transurethral resection of the bladder was initially performed. The mass lesion protruding from inside the bladder was removed, and pus-like fluid was drained. The pathologic diagnosis was eosinophilic cystitis. Follow-up computed tomography showed a remnant mass outside the bladder and urachal cyst. To eliminate the remnant lesion, robot-assisted partial cystectomy was performed. The patient showed no evidence of recurrent disease on follow-up cystoscopy and computed tomography for up to 2 years. CONCLUSIONS: Clinicians should consider the possibility of eosinophilic cystitis in patients who present with hematuria, fever, and suprapubic pain and have both intravesical and extravesical masses.