Functional and histologic imaging of urinary bladder wall after exposure to psychological stress and protamine sulfate

Abstract

To quantify the urinary bladder wall T1 relaxation time (T1) before and after the instillation contrast mixture in rats previously subjected to water avoidance stress (WAS) and/or acute exposure to protamine sulfate (PS). Female Wistar rats were randomized to receive either sham (control) or 1 h of WAS for ten consecutive days before the evaluation of nocturnal urination pattern in metabolic cages. T1 mapping of urinary bladder wall at 9.4 T was performed pre- and post- instillation of 4 mM Gadobutrol in a mixture with 5 mM Ferumoxytol. Subsequently, either T1 mapping was repeated after brief intravesical PS exposure or the animals were sacrificed for histology and analyzing the mucosal levels of mRNA. Compared to the control group, WAS exposure decreased the single void urine volume and shortened the post-contrast T1 relaxation time of mucosa- used to compute relatively higher ingress of instilled Gadobutrol. Compromised permeability in WAS group was corroborated by the urothelial denudation, edema and ZO-1 downregulation. PS exposure doubled the baseline ingress of Gadobutrol in both groups. These findings confirm that psychological stress compromises the paracellular permeability of bladder mucosa and its non-invasive assay with MRI was validated by PS exposure.

Interstitial cystitis—an imbalance of risk and protective factors?

“…Exposure to WAS increases anxiety-like behaviors, urinary frequency, and bladder hyperalgesia. Histological changes in bladder tissue from WAS-exposed rats included ulcerated areas, edema, vascular congestion, inflammatory cell infiltration, increased angiogenesis and mucosal mast cell numbers ( 2 ), and increased bladder mucosal permeability in female Wistar rats ( 167 ). Additionally, Wang et al ( 168 ), reported greater activation in brain regions of the central micturition circuit and increased engagement of portions of the micturition circuit responsive to urgency, viscerosensory perception, and its relay to motor regions coordinating imminent bladder contraction in adult female Wistar-Kyoto rats subjected to WAS to model IC.…”

SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

“…It has been known for over forty years that decreased host resistance [69] is a key determinant of cystitis secondary to the disruption of tissue integrity [12,65,83] or a decrease in the blood supply to the bladder either due to psychogenic stress [82] or abdominal aortic calcification [141]. A recent study reported the non-inferiority of a new triazaacenaphthy-lene antibiotic, Gepotidacin, relative to nitrofurantoin in treating uncomplicated cystitis caused by UPEC and nitrofurantoin-resistant uropathogens [33].…”

“…Compared to men, the higher incidence of cystitis in women is generally linked to their shorter urethra and infrequent voiding [69] that thins the urothelial barrier [12,62,80] for the proximal seeding of uropathogens from the adjacent cavities of the vagina and anus [81]. It is also likely that the periodic shedding of the urothelium, observed exclusively in the females of mammals [82][83][84] may increase the inherent predisposition to cystitis [12] but frequent shedding of urothelium may be lowering the incidence of urothelial carcinoma in women [85,86].…”

“…Furthermore, cystitis can dilate the tight junctions of the inflamed urothelium [12,65,82] to reportedly cause a four-fold rise in creatinine reabsorption [55,67] via passive paracellular diffusion, and the resulting decline in the urine creatinine levels can potentially introduce errors in the estimation of the renal function status of cystitis patients, leading to their under-and overdosing of OAT [25,113]. Given that every dose of an OAT regimen produces an initial subtherapeutic concentration in urine [122] during the intended build-up to the MIC, which is itself indeterminable, there is an inevitable period of potential AMR risk with the initiation of OAT, even with AMS [40,41,[137][138][139].…”

Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration

“…Accordingly, the clearance of diffused drugs from urothelium by venous outflow [42] keeps the urothelial levels of mitomycin [43] or of Gadobutrol static with time regardless of the duration of dwell time or repeated instillation [43][44][45]. The venous clearance of Mitomycin diffusing down the concentration gradient from bladder lumen [46] ensured that urothelial Mitomycin levels remain static during the instillation period [43] but the blood levels of instilled Mitomycin [34,47] and of Gadobutrol exhibited a dynamic range during and after instillation periods(Figure 2A).…”