To confirm changes in urethral activity with age, both intravesical pressure and urethral perfusion pressure (UPP) were recorded and external urethral sphincter electromyography (EUS‐EMG) was performed. A total of 33 female Sprague Dawley rats aged 3 months (young rats), 12 months (middle‐aged rats), and 24 months (aged rats) were used. Bladder activity was evaluated using continuous cystometry. Urethral activity was evaluated by simultaneously recording intravesical pressure and UPP in isovolumetric conditions under urethane anesthesia in each group. Additionally, EUS‐EMG activity was monitored under the same conditions. In continuous cystometry, the amplitude of bladder contractions was not different among the three groups; nevertheless, residual urine volume was significantly increased in middle‐aged and aged rats, as compared in young rats. With respect to UPP, the change in UPP was significantly smaller in aged rats (60%) and middle‐aged rats (64%) than in young rats. Furthermore, the mean amplitude of high‐frequency oscillations of the EUS was significantly lower in aged (61%) and middle‐aged rats (70%) than in young rats. EUS‐EMG revealed EUS bursting activity during voiding with clear active and silent phases in young rats but unclear active and silent phases in aged rats. Masson's trichrome staining of the urethra showed EUS atrophy in aged rats compared to young and middle‐aged rats. The results indicate that aging induces two urethral dysfunctions in the urethral smooth muscle and EUS, which may lead to dyscoordination between the urinary bladder and urethra.

Ipilimumab and nivolumab combination therapy is effective against unresectable or metastatic renal cell carcinoma. However, it is associated with many immune-related adverse events, including hypophysitis that is difficult to diagnose early because of non-specific initial symptoms. Herein, we report the case of a 54-year-old man with metastatic renal cell carcinoma who developed hypophysitis after receiving ipilimumab and nivolumab combination therapy. The initial symptom was headache. However, endocrine tests showed decreased levels of cortisol, free thyroxine and thyroid-stimulating hormone. Moreover, magnetic resonance imaging revealed pituitary enlargement. Accordingly, we diagnosed hypophysitis and immediately started hydrocortisone replacement therapy, which improved the symptoms.

pathway in bladder ischemia. These changes shifted contractile reactivity of ischemic bladder tissues to electrical field stimulation (EFS) to the left and produced cystometric changes consistent with detrusor overactivity. Treatment of bladder tissues with the USF1 inhibitor C527 reversed hyperreactivity to EFS. Treatment of rats with the AMPK-a2 activator AICAR significantly downregulated USF1 expression and diminished cystometric markers of detrusor overactivity in bladder ischemia.CONCLUSIONS: Impairment of AMPK-a2 by ischemia upregulated USF1 and provoked detrusor overactivity by activation of cellular stress responses. The mechanism appeared to involve USF1-directed smooth muscle hyperreactivity via cellular stress signaling pathway. Our data suggest that activators of AMPK-a2 and inhibitors of USF1 may have valuable therapeutic potentials against overactive bladder.