Bladder Research Articles

6402 Unsuspected Bladder Mass Turns Out To Be A Paraganglioma

Abstract Disclosure: S. Lamichhane: None. A. Flowers: None. D.T. Price: None. A. Kaur: None. Background: Urinary bladder (UB) paragangliomas are extremely rare tumors comprising of less than 0.05% of all bladder neoplasms and 10% of all paragangliomas. The diagnosis is usually suspected based on clinical features of painless hematuria, episodic headaches, hypertension, palpitations associated with micturition or bladder and confirmed biochemically by elevated urinary and/or plasma fractionated metanephrines (MN). Here, we present a case of a UB mass that was initially diagnosed on biopsy and subsequent biochemical workup revealed elevated MN. Case Report: A 64-year-old man with type 2 diabetes and hypertension, admitted for revision surgery of subdural hematoma was incidentally found to have a 3.3 x 3.4 x 3.9 cm polypoid heterogenous hyper enhancing UB mass attached to the anterior wall on CT abdomen done for abdominal pain. Cystoscopy and TURBT were complicated by hypertensive urgency. Pathology turned out to be paraganglioma. Detailed history at this time revealed a long-standing history of frequency, urgency, nocturia 4 times nightly, recurrent urinary tract infections, an episode of gross hematuria 1-2 years ago, and difficulty controlling blood pressure on 4 anti-hypertensives. Subsequently, labs showed plasma free MN of 97 pg/ml (ref range <=57), free normetanephrine (NMN) of 2392 pg/ml (ref range <=148), and total MN of 2489 pg/ml (ref range <=205). Genetic panel was negative for SDHA, SHD, AF2, SDHB, SHDC, SDHD, VHL, RET, TMEM127. He received 6 doses of Lantreotide due to suspicion of metastasis based on abdominal, pelvic, and inguinal lymphadenopathy seen on DOTATATE scan. After preparation with alpha and beta blockers, he underwent uneventful robot-assisted cystectomy with lymph node resection that resulted in a well-differentiated paraganglioma negative for margins, lymph node involvement, and extra bladder extension. A week later, MN reduced, plasma free MN 37 pg/ml, free NMN 178 pg/ml, and total plasma MN 215 pg/ml. His BP improved, and micturition-induced palpitations resolved. Conclusion: Due to the rarity of UB paraganglioma, the diagnosis can be missed and delayed. This has a serious implication due to the risk of hypertensive crisis during the surgery and increased risk of cardiovascular complications. This case highlights the need for awareness among physicians of the clinical presentation associated with UB paraganglioma, its early recognition and management. Presentation: 6/2/2024

Comparison of pelvic floor morphometry in supine and standing in women with and without pelvic organ prolapse: A cross-sectional exploratory study

Introduction:Intra-abdominal pressure (IAP) and gravity may both challenge pelvic organ support and contribute to the development or worsening of pelvic organ prolapse (POP). This study aimed to assess whether pelvic floor morphometry differs between supine and standing positions in women with and without POP, at rest and with elevated IAP, and to compare the change in measures from the supine to standing position between groups. Methods:Thirty premenopausal vaginally parous women with (n=15) and without (n=15) POP were included. Transperineal ultrasound was used to assess pelvic floor morphometry (bladder neck [BN], rectal ampulla [RA], levator plate angle [LPA], anorectal angle [ARA], levator anteroposterior distance [LAP], and levator hiatal area [LHA]) in supine and standing, at rest and bearing down. Measures were compared between positions (supine and standing) and groups (women with and without POP). Results:At rest, BN and RA were lower and LPA was smaller in standing than supine for all participants (all p<0.04), and LHA and LAP distance were greater in standing than supine for women with POP (p<0.001). In standing rest, BN and RA were lower and LHA was greater in women with than without POP (p<0.001). There were no differences between women with and without POP in these measures in supine (all p>0.23). ARA was greater in with POP than without POP in both positions at rest (p=0.002). During bearing down, BN and RA were lower, ARA and LPA were smaller, and LHA and LAP distance were larger in standing than in supine for all participants (all p<0.023). In bearing down in both positions, BN and RA were lower and ARA and LHA were greater in women with than without POP (all p=0.013). Conclusion:Our findings indicate lower pelvic floor support in women with POP compared to women without POP that is evident during bearing down in supine, and at rest and during bearing down in standing. These findings underscore the utility of transperineal ultrasound to assess pelvic floor morphometry in standing to guide management of women with POP.

Urinary Bladder Stone Secondary to Transmigration of Intra Uterine Contraceptive Device

Urinary Bladder Stone Secondary to Transmigration of Intra Uterine Contraceptive Device

6694 A Case of an Extraneous Organ: A Uterus Found in a Genotypic and Phenotypic Male

Abstract Disclosure: R.A. Zielinski: None. S. Shteyman: None. A.G. Samat: None. Background: Persistent Mullerian Duct Syndrome (PMDS) is a rare entity that occurs when a phenotypic male is found to have female reproductive organs. In our case we describe an XY male who was found to have an abdominal mass consistent with a uterus on pathology. Clinical Case: Our patient is a 58-year-old male with hypertension, obesity, and obstructive sleep apnea who presented to the ED with 3 weeks of left upper quadrant pain. Abdominal CT showed two homogeneous enhancing oval lesions in the pelvis superior to the urinary bladder; 8.3 x 4.6 cm on the right and 3.6 x 3 cm on the left. Exploratory laparotomy was performed, and intraoperatively the mass was firm with a left satellite lesion and two fibrous bands that appeared similar in structure to round ligaments. Microscopically the tissue contained mullerian-type epithelium and smooth muscle with cystic degeneration. It was CK7 positive, estrogen receptor variable positive, and CK20 negative. Genetic testing confirmed the patient’s karyotype to be XY without genetic mosaicism. Our patient had two children spontaneously, regular spontaneous erections, and occasional hot flashes. Physical exam revealed an obese male (BMI 51) with bilateral gynecomastia and normal testicular size. He had no history of intra-abdominal or undescended testes requiring surgery. Labs showed increased total estrogen (283.7 pg/mL, n 60-190 pg/mL) and estradiol (39 pg/mL, n &amp;lt;= 29 pg/mL), decreased total testosterone (86 ng/dL, n 250-1,100 ng/dL), and normal free testosterone when corrected for SHBG (140 ng/dL, n 110-574 ng/dL). Testicular ultrasound was unrevealing. 3 years postoperatively his estradiol level normalized (34 pg/mL) and his total testosterone improved from 86 ng/dL to 223 ng/dL after losing 40 pounds on semaglutide. Discussion and Conclusion: Although the exact incidence of PMDS is unknown, it is a rare phenomenon. Only 200 cases between 1964 and 2000 and 34 cases between 2013 and 2017 have been reported. Mullerian ducts are embryologic structures present in both XY and XX fetuses until week 8 of life, when XY fetuses produce anti-mullerian hormone (AMH). In PMDS, the XY fetus either fails to produce AMH, or there is a defect in the AMH receptors, leading to the persistence of mullerian ducts. These ducts can then differentiate into a uterus, fallopian tubes, and/or the upper vagina. Our patient is a genotypical and phenotypical male with a uterus-like organ. The mild elevation in his estrogen level is likely secondary to his obesity. The estrogen could have increased the size of the uterus, causing the patient’s initial symptoms of abdominal pain which prompted his presentation to the hospital.

Suspected encrusting cystitis in a domestic ferret (Mustela putorius furo)

BackgroundEncrusting cystitis diagnosis and medical management in domestic ferrets (Mustela putorius furo) has never been documented. Case descriptionA client-owned, 6.5-year-old, neutered, male domestic ferret was presented for lethargy, abdominal pain, straining to urinate for 12 days, and red, purulent urine. On physical examination, the ferret was quiet, alert, and responsive, had a distended and inexpressible bladder, large and firm kidneys, and was displaying signs of severe pain including vocalization on abdominal palpation and when attempting to urinate. Sonographic evaluation showed an irregular, layered, hyperechoic mass lesion present in the lumen of the urinary bladder with extensions of the layered luminal material into the urethra, and severely dilated renal pelves and ureters. These severe, urinary bladder changes were consistent with pseudomembranous, encrusting cystitis. Following a discussion with the owner about options for humane euthanasia versus exploratory surgery, euthanasia was elected. The remains were taken home with the owner and a necropsy was not performed. Conclusion and case relevanceTo the author’s knowledge, this paper reports the first known case of suspected encrusting cystitis in a domestic ferret including radiologic and ultrasonographic findings.

Excretory urography can track down morphological changes in the urinary bladder associated with urachal anomalies in calves for early diagnosis.

To investigate radiographic detection by excretory urography of morphological changes in the urinary bladder associated with urachal anomalies in calves. Excretory urography was performed to detect morphological changes in the urinary bladder of 13 calves, of which 6 were nondysuric with swelling of umbilical region and 7 were dysuric without clinical umbilical swelling from November 2022 through April 2024. The urinary bladder was delineated in all 13 calves after excretory urography. The aspect ratios (length:height), which objectively evaluate the shape of the urinary bladder, ranged from 1.08 to 2.43 (1.90 in average) and 1.34 to 11.89 (4.75 in average) in nondysuric and dysuric calves, respectively. The ratios of calves with nondysuric were significantly lower than those of dysuric (P < .05). Excretory urography could play an important role in evaluating abnormal morphological changes due to urachus anomalies in the urinary bladder of calves. Among calves with dysuria, urachal anomaly should be included in the differential diagnosis. Excretory urography is proposed as an alternative option for early diagnosis among calves presenting with dysuria to improve livestock productivity.

Primary Melanoma of the Urinary Bladder: Clinical, Histopathologic, and Comprehensive Molecular Analysis of a Rare Tumor.

Primary melanoma of the urinary bladder is extremely rare and generally has a poor prognosis. The histopathological diagnosis can be challenging as tumors can be unpigmented and of varying morphology. Here we report a rare example of primary urinary bladder melanoma with clinical, imaging, gross anatomical, histopathologic, immunohistochemical, and molecular findings to illustrate the utility of an integrated approach in establishing the diagnosis and guide therapy. A comprehensive, integrated approach, including molecular studies, may be helpful in further establishing an accurate diagnosis and informing therapies of this rare but poorly behaved entity.

Primary urinary bladder lymphoma: presentation with bilateral hydronephrosis

Primary urinary bladder lymphoma: presentation with bilateral hydronephrosis

APRIL/BAFF upregulation is associated with clonal B-cell expansion in Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a chronic inflammatory disease of the urinary bladder with an unknown etiology. We conducted comprehensive immunogenomic profiling of bladder specimens obtained by biopsy and cystectomy from 37 patients with HIC. Next-generation RNA sequencing demonstrated abundant plasma cell infiltration with frequent light chain restriction in HIC-affected bladder tissue. Subsequent analysis of the B-cell receptor repertoire revealed spatial and temporal expansion of B-cell clones. The extent of B-cell clonal expansion was significantly correlated with the gene expression levels of TNFSF13 and TNFSF13B, which encode APRIL and BAFF, respectively. These findings indicate that APRIL and BAFF are the key regulators of clonal B-cell expansion in HIC and might serve as therapeutic targets in this debilitating disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

EZH2 specifically regulates ISL1 during embryonic urinary tract formation

Isl1 has been described as an embryonic master control gene expressed in the pericloacal mesenchyme. Deletion of Isl1 from the genital mesenchyme in mice leads to an ectopic urethral opening and epispadias-like phenotype. Using genome wide association methods, we identified ISL1 as the key susceptibility gene for classic bladder exstrophy (CBE), comprising epispadias and exstrophy of the urinary bladder. The most significant marker (rs6874700) identified in our recent GWAS meta-analysis achieved a p value of 1.48 × 10− 24 within the ISL1 region. In silico analysis of rs6874700 and all other genome-wide significant markers in Linkage Disequilibrium (LD) with rs6874700 (D’ = 1.0; R2 > 0.90) revealed marker rs2303751 (p value 8.12 × 10− 20) as the marker with the highest regulatory effect predicted. Here, we describe a novel 1.2 kb intragenic promoter residing between 6.2 and 7.4 kb downstream of the ISL1 transcription starting site, which is located in the reverse DNA strand and harbors a binding site for EZH2 at the exact region of marker rs2303751. We show, that EZH2 silencing in HEK cells reduces ISL1 expression. We show that ezh2−/− knockout (KO) zebrafish larvae display tissues specificity of ISL1 regulation with reduced expression of Isl1 in the pronephric region of zebrafish larvae. In addition, a shorter and malformed nephric duct is observed in ezh2−/− ko zebrafish Tg(wt1ß:eGFP) reporter lines. Our study shows, that Ezh2 is a key regulator of Isl1 during urinary tract formation and suggests tissue specific ISL1 dysregulation as an underlying mechanism for CBE formation.

Reconstruction of deep and perforating corneal defects in dogs-A review (Part II/III): Biomaterials and keratoprosthesis.

The surgical reconstruction of severe corneal ulcers is a common and crucial component of the clinical practice of veterinary ophthalmology. Numerous surgical techniques are used in dogs for corneal reconstruction, and these techniques may be categorized by the material used to repair the corneal lesion. The first part of the present review described procedures that utilize autogenous ocular tissues, homologous donor tissues, and heterologous donor tissues. In this second part of the review, the categories of biomaterials and keratoprosthetics will be summarized. Biomaterials that are reported for use in dogs include amniotic membrane, porcine urinary bladder acellular matrix, porcine small intestinal submucosa, acellular porcine corneal stroma, and other miscellaneous soft tissue and cartilage grafts (e.g., preserved equine renal capsule, autologous omentum, autologous buccal mucosa membrane, bovine pericardium, and homologous peritoneum). Descriptions of keratoprosthesis surgery in dogs are currently limited, but the use of artificial corneal transplants hold promise for dogs with severe, vision-compromising corneal disease that is not amenable to other reconstruction techniques. This review describes the results of experimental studies evaluating these graft materials in dogs, and it will summarize the findings and outcomes of the clinical articles published in each material category. Reporting inconsistencies and areas where additional research is required will be highlighted to help guide future studies in this area. A major aim of this review is to help identify potential subjects that could be evaluated in future investigations and that might lead to refinements in clinical practice.

H4K20me3 is increased in human bladder cancer tissues, and it is upregulated by reactive oxygen species in bladder cancer cell lines.

H4K20me3 is increased in human bladder cancer tissues, and it is upregulated by reactive oxygen species in bladder cancer cell lines.

Neurogenic-derived 6-nitrodopamine is the most potent endogenous modulator of the mouse urinary bladder relaxation

6-Nitrodopamine (6-ND) modulates vas deferens, seminal vesicles, and corpus cavernosum contractility; however, its role on the lower urinary tract organs has not been evaluated. Investigations of isolated urinary bladders from wild-type (WT) mice revealed 6-ND release was comparable to that of dopamine and adrenaline, whereas noradrenaline was hardly detected, as assessed by liquid chromatography coupled to tandem mass spectrometry. In vitro, 6-ND induced concentration-dependent relaxations in carbachol pre-contracted bladders with high potency (pEC50: 8.04 ± 0.86), independently of eNOS/sGC activity. Co-incubation of 6-ND (1–10 μM) antagonizes the contractile effects of acetylcholine (p < 0.05). Experiments using nitric oxide synthase (NOS) knockout mice demonstrated that 6-ND release from isolated urinary bladder was significantly reduced by neuronal NOS (nNOS−/−) deletion and abolished by triple NOSs deletion (n/i/eNOS−/−), while no significant changes were observed in endothelial (eNOS−/−) or inducible (iNOS−/−) knockout mice. Incubation with tetrodotoxin resulted in a significant decrease in 6-ND release in bladders obtained from WT, but not in nNOS−/− mice. The bladders from nNOS−/− and n/i/eNOS−/− mice exhibited significantly higher contractile responses to electric field stimulation (EFS), compared to eNOS−/−, iNOS−/−, or WT bladders. The hyperreactivity observed in triple NOS knockouts was reversed by the incubation with bladder mucosal layer obtained from a donor WT mice, but not with the muscular layer. These findings clearly demonstrate 6-ND is the most potent endogenous relaxing agent of urinary bladder, and inhibition of its release is associated with bladder hyperreactivity.

The first survey of endoparasite infection in the brown rat (Rattus norvegicus) from a synanthropic environment in Hungary

Urban rats are significant reservoirs of zoonotic endoparasites, posing serious health risks to humans. This study aimed to detect common endoparasites in wild brown rats (Rattus norvegicus) in Budapest, addressing the current lack of endoparasite surveys in Hungary. Carcasses of 131 rats collected following extermination were examined. Three zoonotic helminths were identified: Hymenolepis nana and Hymenolepis diminuta in the jejunum, and Calodium hepaticum in the liver. Additionally, non-zoonotic parasites were detected, including Eimeria spp., Entamoeba muris, Heterakis spumosa, Nippostrongylus brasiliensis, Eucoleus gastricus, Aonchotheca annulosa, Syphacia muris (intestine), and Trichosomoides crassicauda (urinary bladder). Helminth infection prevalence was 83.9 %, with no noticeable differences in prevalence or infection intensity between sexes. These findings highlight the potential public health risk posed by zoonotic parasites in urban rat populations, emphasising the importance of surveillance to mitigate possible human infection. The findings indicate that rats from Budapest harbour similar parasites to those in neighbouring regions. Further large-scale studies are recommended to better understand the parasitic landscape in Hungary's rat populations, leveraging data from rat control programs.

The onset characteristics and prognosis of patients with radiation-associated second primary malignancy: a pancancer study in the US SEER cancer registries.

Cancer survivors have an elevated risk of developing a second primary malignancy (SPM) after radiation therapy (RT). Data on the association between RT and SPM are limited. Our aim was thus to investigate the impact of RT on the risk of developing SPMs and to evaluate the specific characteristics and prognostic outcomes. We enrolled a pancancer cohort using data from the Surveillance, Epidemiology, and End Results registries spanning from January 1973 to December 2015. Multivariable Cox and the Fine-Gray competing risk regression were employed to assess the hazard ratio (HR) and 95% confidence interval (CI) of SPMs in patients who received RT in comparison to those with no RT (NRT). Poisson regression was used to evaluate the RT-associated risks (RR) and the standardized incidence ratio (SIR) for SPMs. The analysis identified 24 types of risk-increased SPMs (RI-SPMs), including malignancies of the oropharynx, hypopharynx, larynx, esophagus, lung, breast, liver, pancreas, stomach, colon, rectum, ovary, corpus uteri, ureter, vagina, urinary bladder, penis, testis, and kidney, among others. The cumulative incidence of those with RI-SPMs was higher than that of the NRT patients (19.8% vs. 15.3%; P<0.001). The RR for RI-SPMs decreased with increasing age at FPM diagnosis (aged 20-49 years: RR 1.52; age 50-69 years: RR 1.31; age 70 years: RR 1.21), and the RR increased with longer latency period following FPM diagnosis (60-119 months: RR 1.28; 120-239 months: RR 1.24; 240-360 months: RR 1.46). The 10-year overall survival of those with RI-SPMs was significantly lower than that of the matched NRT patients (28.5% vs. 31.7%; P<0.001). Patients with RI-SPMs warrant greater attention given their time-cumulative onset risk and poor prognosis. Long-term surveillance is necessary for cancer survivors treated with RT.

Metformin: Beyond Type 2 Diabetes Mellitus.

Metformin was developed from an offshoot of Guanidine. It is known to be the first-line medication for type 2 diabetes mellitus, polycystic ovarian syndrome, and weight reduction. Metformin has also been shown to have effectiveness in the management of non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, and various carcinomas like hepatocellular, colorectal, prostate, breast, urinary bladder, blood, melanoma, bone, skin, lung and so on. This narrative review focuses on the effect of metformin on non-alcoholic fatty liver disease, liver cirrhosis, and hepatocellular carcinoma. The search platforms for the topic were PubMed, Scopus, and Google search engine. Critical words for searching included 'Metformin,' AND 'Indications of Metformin,' AND 'Non-Alcoholic Fatty Liver Disease,' AND 'Metformin mechanism of action,' AND 'NAFLD management,' AND 'NAFLD and inflammation,' AND 'Metformin and insulin,' AND 'Metformin and inflammation,' AND 'Liver cirrhosis,' AND 'Hepatocellular carcinoma.' Lifestyle modification and the use of hypoglycemic agents can help improve liver conditions. Metformin has several mechanisms that enhance liver health, including reducing reactive oxygen species, nuclear factor kappa beta (NF-κB), liver enzymes, improving insulin sensitivity, and improving hepatic cell lipophagy. Long-term use of metformin may cause some adverse effects like lactic acidosis and gastrointestinal disturbance. Metformin long-term overdose may lead to a rise in hydrogen sulfide in liver cells, which calls for pharmacovigilance. Drug regulating authorities should provide approval for further research, and national and international guidelines need to be developed for liver diseases, perhaps with the inclusion of metformin as part of the management regime.

Robot-assisted T-plasty for recalcitrant bladder neck stenosis: description of technique and initial results.

The aim of this study was to describe the technique and initial outcomes of robot-assisted T-plasty for recalcitrant bladder neck stenosis. Patients who underwent robot-assisted T-plasty for recalcitrant bladder neck stenosis in a single center were included. Presence of bladder neck stenosis was preoperatively confirmed by the combination of retrograde urethrography with voiding cysto-urethrography and flexible urethroscopy. Follow-up visits were performed with history taking, uroflowmetry and echographic residual urine measurement. Complications were graded according to the Clavien-Dindo classification. Patients without urinary symptoms and with a maximum uroflow of no less than 15mL/s were considered as successfully treated. Otherwise, cystoscopy would be performed, and recurrence was defined as the inability to pass a 14 French cystoscope through the bladder neck. Since 2018, seven patients were treated. The etiologies were transurethral resection of the prostate and simple prostatectomy in respectively 6 patients and 1 patient. Cystoscopy was able to diagnose bladder neck stenosis in all cases whereas urethrography was equivocal in 3 out of 7 cases. Median (range) age at surgery was 60 (54-75) years, and median number of prior endoscopic treatment for bladder neck stenosis was 3 (1-16). The median operative time was 123 (110-159) minutes. No intraoperative complications were reported. Three patients suffered a grade 2 complication. After a median follow-up of 27 (4-74) months, the recurrence-free rate was 100% with no evidence of de-novo incontinence or erectile dysfunction. In our series, robot-assisted T-plasty suggests positive and safe outcomes in treating recalcitrant bladder neck stenosis with a good patency rate and low incontinence rate. Additionally, cystoscopy is reliable in the diagnosis of patients with inconclusive urethrography results.

El uso de la cirugía robótica para el tratamiento de estenosis uretrales y contracturas del cuello vesical: una revisión sistemática

The use of robotic surgery for the management of urethral strictures and bladder neck contractures: a systematic reviewObjective: The aim of this systematic review is to offer a comprehensive view of the current use of robotic surgery for the treatment of urethral strictures and bladder neck contractures.Methods: A systematic review of the current literature was conducted through the Medline and NCBI PubMed, Embase databases in December 2023. Keywords used were “robotic” and “robotic-assisted” combined with “urethroplasty”, “urethral stricture”, and “bladder neck contracture”. All papers published after 2000, concerning studies conducted on humans for urethral strictures and bladder neck contractures managed with robotic surgery were considered for the review. Only procedures involving a direct approach to urethra/bladder neck and/or graft harvesting for urethroplasty have been included.Results: A total of 275 articles were evaluated after the strategy search and only 11 articles were considered eligible for the final analysis. The studies included a series of between a minimum of 1 and a maximum of 104 patients, for a total of 203 patients. The robotic surgery was performed mainly for the treatment of bladder neck contracture and posterior urethra. In some reports, the robotic system was used for graft harvesting, subsequently used with an open perineal technique. The follow-up presented in the different studies is very heterogeneous. However, most studies have high success rates, with recurrence and redo surgery rates generally below 20%. Likewise, post-procedure incontinence rates are low.Conclusions: The outcomes presented in the literature, combined with the minimally invasive nature, suggest a possible growing role for robotic surgery in the coming years in the treatment of these diseases.

Activation mechanism and novel binding sites of the BKCa channel activator CTIBD.

The large-conductance calcium-activated potassium (BKCa) channel, which is crucial for urinary bladder smooth muscle relaxation, is a potential target for overactive bladder treatment. Our prior work unveiled CTIBD as a promising BKCa channel activator, altering V 1/2 and G max This study investigates CTIBD's activation mechanism, revealing its independence from the Ca2+ and membrane voltage sensing of the BKCa channel. Cryo-electron microscopy disclosed that two CTIBD molecules bind to hydrophobic regions on the extracellular side of the lipid bilayer. Key residues (W22, W203, and F266) are important for CTIBD binding, and their replacement with alanine reduces CTIBD-mediated channel activation. The triple-mutant (W22A/W203A/F266A) channel showed the smallest V 1/2 shift with a minimal impact on activation and deactivation kinetics by CTIBD. At the single-channel level, CTIBD treatment was much less effective at increasing P o in the triple mutant, mainly because of a drastically increased dissociation rate compared with the WT. These findings highlight CTIBD's mechanism, offering crucial insights for developing small-molecule treatments for BKCa-related pathophysiological conditions.

122 - Functional role of the urothelium in nitrergic signaling in the isolated healthy and inflamed rat urinary bladder

122 - Functional role of the urothelium in nitrergic signaling in the isolated healthy and inflamed rat urinary bladder