Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity

Abstract

Objective:To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO.Materials and Methods:Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed.Results:The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group.Conclusions:It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.

Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat

“…Our results show increased MC numbers and MCT expression in the rat bladders with CBI. Previous studies suggested that increased MC–nerve interaction might be a cause of bladder hyperactivity [ 10 , 26 ]. Keith and Saban [ 26 ] reported an intimate anatomic relationship between MCs and primary afferent nerve fibers in the guinea pig bladder and concluded that the imbalance in this mutual exchange could potentially cause bladder hyperactivity.…”

“…The bladder was processed for methylene blue staining and immunohistochemical staining. The number of MCs was counted in 5 consecutive fields (×400), and the mean values were used in the subsequent statistical analysis [ 10 ]. For immunohistochemical examinations of bladder tissue, sections were deparaffinized, and endogenous peroxidase was quenched with 0.3% H 2 O 2 .…”

“…A previous study revealed that MC infiltration into the bladder was observed in patients with detrusor overactivity (DO), which caused OAB [ 9 ]. It was also reported that MC infiltration into the bladder plays an important role in DO in rats with visceral hypersensitivity [ 10 ]. Mast cell tryptase (MCT), the most abundant MC protease, modulates neuronal activity by cleaving protease-activated receptor 2 (PAR2), which is expressed on C fibers.…”

The evolution of nucleosidic analogues: self-assembly of prodrugs into nanoparticles for cancer drug delivery

“…A prodrug can be designed to convert to its active form by counting on its bioconversion by an enzyme expressed largely in the targeted tissue or organ. 73,74 Xu et al utilized the increased presence of the cathepsin B enzyme in the pancreatic cancer tissue to develop a cholesteryl hemisuccinate-1 gemcitabine prodrug that will release the gemcitabine mainly at the cancer site aer contact with cathepsin B that will cleave the amide bond. 75…”