Cold stress-induced bladder overactivity in type 2 diabetic mellitus rats is mitigated by the combination of a M3 -muscarinic antagonist and a ß3 -adrenergic agonist.

OBJECTIVES: Goto-Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M3 -muscarinic receptor antagonist and a ß3 -adrenergic receptor agonist. METHODS: Ten-week-old female GK rats were fed a high-fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle, the M3 -muscarinic receptor antagonist solifenacin, the ß3 -adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4 ± 2°C), where the cystometric measurements were continued. The expressions of both M3 -muscarinic and ß3 -adrenergic receptors were investigated. RESULTS: After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle-, solifenacin-, or mirabegron-treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M3 -muscarinic and ß3 -adrenergic receptors were detected, the expression of M3 -muscarinic receptor mRNA was significantly higher than that of ß3 -adrenergic receptor mRNA. CONCLUSIONS: The cold stress-induced bladder overactivity was not improved by either the M3 -muscarinic receptor antagonist or the ß3 -adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M3 -muscarinic antagonists and ß3 -adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.

[Docetaxel-based chemotherapy for hormone-refractory prostate cancer in Japanese patients : experience in a single institute].

Between April 2007 and November 2010, we treated 21 cases of hormone-refractory prostate cancer with docetaxel-based chemotherapy. The administered dose of docetaxel was from 40 to 75 mg/m2, and the treatments were repeated every 3 to 4 weeks. The patients were from 61 to 88 years old (median 78). Fourteen patients were alive, and seven had died. According to the prostate specific antigen response, the complete response rate was 30%, partial response was 10%, no change was 25%, and progressive disease was 25%, respectively. Median time to progression was 7.0 months (from 1 to 43 months), and median overall survival time after chemotherapy was 11.5 months (from 3 to 44 months). One patient died of adverse events. However, in most cases, hematological toxicities were tolerable and manageable, although neutropenia of grade 3 to 4 was observed. On the other hand, non-hematological toxicities that led to discontinuation of the therapy were observed in a few cases. Docetaxel-based chemotherapy was feasible and effective even for patients over 80 years old. In responding cases, it is important to maintain the chemotherapy as long as possible, by modifying the treatment procedures, while paying attention to the adverse events.