Akiyoshi Someya

Effect of mirabegron, a novel β3-adrenoceptor agonist, on bladder function during storage phase in rats

Mirabegron, a selective β3-adrenoceptor agonist, facilitates urine storage function by exerting a relaxing effect on bladder smooth muscle. Here, we investigated the effect of mirabegron on bladder function during the storage phase. We assessed the effect of mirabegron on the resting intravesical pressure in anesthetized rats and also tested antimuscarinics (oxybutynin and tolterodine) under the same experimental conditions. Mirabegron dose-dependently decreased the resting intravesical pressure, while oxybutynin and tolterodine showed no statistically significant effects on resting intravesical pressure. We also investigated the effect of mirabegron on bladder function using cystometry technique in conscious rats with bladder outlet obstruction. While mirabegron dose-dependently decreased the frequency of nonvoiding contractions, considered an index of abnormal response in bladder storage, no significant effects were noted on the amplitude of nonvoiding contractions, micturition pressure, threshold pressure, voided volume, residual volume, or bladder capacity. Neither oxybutynin nor tolterodine affected the frequency of nonvoiding contractions; however, oxybutynin increased residual volume and tended to decrease voided volume in a dose-dependent manner, and tolterodine dose-dependently decreased voided volume. Taken together, these results shed light on the suggestion of mirabegron as a therapeutic agent, compared with antimuscarinics, with its most prominent effect being the facilitation of bladder storage.

EFFECTS OF MIRABEGRON (YM178) ON NON-MICTURITION CONTRACTIONS IN THE BLADDER OF CONSCIOUS RATS WITH BLADDER OUTLET OBSTRUCTION (BOO)

patients within the development cohort was 26 vs. 71 months in the external validation cohort (P<0.001). In overall survival analyses, the median values were 21 vs. 32 months for respectively the development and the external validation cohort (P<0.001). Three variables (age, stage and surgical status) were included in the nomograms predicting cancer-specific and overall mortality. In the external validation cohort, the nomograms achieved between 72 and 80% accuracy for prediction of ACC-specific or overall mortality at 1 to 5 years after either surgery or diagnosis of ACC for non-surgical patients. CONCLUSIONS: Our models are the first standardized and individualized prognostic tools for patients with ACC. Their accuracy was confirmed within a large external population-based cohort of ACC patients.