Long term-side effects from cancer therapies are a growing health care concern as life expectancy among cancer survivors increases. Damage to the bladder is common in patients treated with radiation therapy for pelvic cancers and can result in radiation (hemorrhagic) cystitis (RC). The disease progression of RC consists of an acute and chronic phase, separated by a symptom-free period. Gaining insight in tissue changes associated with these phases is necessary to develop appropriate interventions. Using a mouse preclinical model, we have previously shown that fibrosis and vascular damage are the predominant pathological features of chronic RC. The goal of this study was to determine the pathological changes during acute RC. We identified that radiation treatment results in a temporary increase in micturition frequency and decrease in void volume 4–8 weeks after irradiation. Histologically, the micturition defect is associated with thinning of the urothelium, loss of urothelial cell–cell adhesion and tight junction proteins and decrease in uroplakin III expression. By 12 weeks, the urothelium had regenerated and micturition patterns were similar to littermate controls. No inflammation or fibrosis were detected in bladder tissues after irradiation. We conclude that functional bladder defects during acute RC are driven primarily by a urothelial defect.
Fetal alcohol spectrum disorders (FASD) is an overarching term that encompasses a range of developmental outcomes exhibited in children exposed to alcohol in utero. 1 FASD can present differently in every child, however, intellectual and/or behavioral impairments are always reported. The most severe of these disorders is Fetal Alcohol Syndrome (FAS), which is characterized by facial dysmorphology, growth restriction, and central nervous system/neurodevelopmental abnormalities. 2 As a result, the US Surgeon General and the American Academy of Pediatrics have issued an advisory to abstain from any alcohol when considering pregnancy and throughout pregnancy. 3,4 Although the exact mechanism of FASDs remains elusive, the Mechanistic Target
Purpose:
We sought to determine if urinary cytokine concentration profiles were different between various bladder conditions.
Materials and Methods:
Participants at three clinical sites completed a demographics survey and provided a urine sample in a collection cup containing a room-temperature urine preservative. Participants were divided into the following categories based on physician-documented diagnosis: asymptomatic control, nonulcerative interstitial cystitis (IC), overactive bladder with incontinence (OAB wet), urinary tract infection (UTI), and bladder cancer. Urinary cytokines were measured through Luminex multiplex assay.
Results:
Two hundred and seventy-seven urine samples were collected from three clinical sites. Urinary pro-inflammatory cytokines had an increasing trend in bladder disease versus control, with a significant increase for chemokine (C-X-C) ligand 1 growth-regulated protein alpha CXCL1 (GRO). Further analyses demonstrated that patients with UTI had significantly higher levels of GRO and interleukin-8 (IL-8) in comparison to control, nonulcerative IC, OAB wet, and bladder cancer. Both are chemokines that stimulate chemotaxis resulting in the rapid accumulation of immune cells such as neutrophils. IL-6 levels overall were at the lower limit of assay range but were significantly increased in urine of UTI patients versus IC patients. MCP-1 (CCL2) had the least separation among the control group and the various bladder diseases.
Conclusion:
Urinary concentrations of GRO were higher in disease state compared to control. Specifically, levels of GRO and IL-8 were higher in urine samples from patients with UTI compared to controls and other bladder conditions. Comparing and contrasting urinary cytokines may help improve our understanding of these important bladder diseases with great unmet needs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.