Hemorrhagic cystitis is a common complication in children receiving cyclophosphamide, a chemotherapeutic alkylating agent. Acrolein is a urinary metabolite from cyclophosphamide and can induce hemorrhagic cystitis. Here, we investigated the effects and mechanisms of acrolein by intravesical instillation on urinary bladder muscle contractions and pathological alterations in rats. Acrolein instillation significantly increased the muscle contractions of rat bladder detrusor after 1 and 6 h but markedly decreased detrusor contractions after 24 h. Acrolein increased phosphorylated protein kinase C (pan-PKC) expressions in bladders after 1 and 6 h but inhibited it after 24 h. Inducible nitric oxide (NO) synthase (iNOS) protein expressions were markedly induced in bladders 24 h after acrolein treatment. Twenty-four-hour acrolein instillation increased the levels of nitrite/nitrate and interleukin-6 (IL-6) in the urinary bladder. The iNOS inhibitors significantly inhibited the acrolein-increased nitrite/nitrate levels, but not IL-6 levels. IL-6-neutralizing antibodies effectively inhibited the acrolein-increased NOx levels. The increased detrusor contractions by 1-h acrolein treatment were significantly reversed by the PKC inhibitor RO32-0432, and the decreased detrusor contractions by 24-h acrolein treatment were significantly reversed by the iNOS inhibitor and IL-6-neutralizing antibody. Both the iNOS inhibitor and IL-6-neutralizing antibody effectively reversed the increased iNOS expression, decreased PKC phosphorylation, increased bladder weight, and hemorrhagic cystitis in rats 24 h after acrolein treatment. Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling pathway participates in the acrolein-triggered detrusor contraction inhibition and hemorrhagic cystitis. These findings may help us to find a new strategy to treat cyclophosphamide-induced hemorrhagic cystitis.
Normal ECG values in newborns, infants, and children have been collected and published. ECG in the adolescent, however, remains, to be collected and studied. The present study was designed and carried out to establish the normal ECG standards in male and female adolescents. A total of 898 school children and adolescents screened and examined as healthy were divided by age and sex into 6-9, 9-13, and 13-18 years age-groups. A 12 lead conventional ECG was recorded in 10 mm/mV and 25 mm/s, utilizing an automated Fukuda Denshi FCP-4301, MS-DOS/IBM-AT ECG machine. Lead V3R was not taken. Analog-to-digital conversion was performed by Fukuda signal acquisition module at a sampling rate of 500 Hz. The data on 69 ECG parameters were analyzed for the mean, standard deviation, 2nd to 98th percentiles, 95% confidence intervals, and sex difference. Normal values on 69 ECG parameters, sex-specific heart rate, P-QRS-T interval, duration, axis, wave amplitude, and calculated R/S amplitude ratio and ventricular activation time by age-group and sex were established. Male and female difference was noted in 49 (71.0%) parameters, of which 3 (6.1%) began in 6-9 years age-group, 30 (61.2%) began in 9-13 years age-group, and 16 (32.7%) in 13-18 years age-group. No sex difference occurred in 20 (29.0%) parameters. Normal male and female ECG standards on 69 ECG parameters in the adolescent were established. ECG sex difference began to appear the earliest at ages 6-9 years, and it occurred mostly at ages 9-13 years and 13-18 years, reflecting the anatomical and physiological consequences of puberty.
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.