Pelvic tissue from women with stress urinary incontinence and pelvic organ prolapse show a genetic predisposition to abnormal extracellular matrix remodeling, which is modulated by reproductive hormones, trauma, mechanical stress load and aging. This progressive remodeling contributes to stress urinary incontinence/pelvic organ prolapse by altering normal tissue architecture and mechanical properties.
The finding of stage 2 or greater cystocele is highly suggestive of clinically significant apical vaginal descent to -3 or greater. Furthermore, as cystocele stage increases, the predictive value of apical prolapse also increases. Surgeons contemplating cystocele repair should have high suspicion for vaginal apical prolapse and consider concomitant repair.
The open probability of calcium-activated voltage-gated potassium channel (BK channel) on bladder umbrella urothelial cells is increased by lipopolysaccharide (LPS). It is hypothesized that this channel’s activity is important in the urothelial innate immune response during urinary tract infection (UTI). We performed in vivo studies using female C57BL/6 mice whose bladders were inoculated with LPS (150 μl of 1 mg/ml) or uropathogenic Escherichia coli (UPEC, UTI89), without and with intravesical BK inhibitor iberiotoxin (IBTX, 1 μM). Inflammatory biomarkers (chemokines and cytokines) were measured in urine specimens collected 2 h after inoculation using a 32-multiplex ELISA. Of these 32 biomarkers, 19 and 15 were significantly elevated 2 h after LPS and UPEC exposure, respectively. IBTX significantly abrogated the elevations of 15 out of 19 biomarkers after LPS inoculation and 12 out of 15 biomarkers after UPEC inoculation. In a separate experiment, qPCR for IL-6, interferon-γ-induced protein 10 (CXCL10), and macrophage inflammatory protein 2 (CXCL2) in urothelium paralleled the changes measured in urine of these same biomarkers, supporting that urinary changes in biomarker levels reflected urothelial expression changes. These in vivo data demonstrated that BK channel activity is crucial in the urothelial host innate immune response, as measured by changes in urinary biomarkers, in UTI pathogenesis.
OVX mice persisted with increased voiding frequency after LPS. Urothelial genes that could mediate this voiding behavior include IL6, COX-2, and S-adenosylmethionine decarboxylase.
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