Akihiko Shibuya

Dopamine release in the medial preoptic area during male copulatory behavior in rats

In vivo microdialysis was employed to measure the extracellular concentrations of dopamine (DA) in the medial preoptic area (MPOA) of rats during male sexual activity to look for a correlation with sexual activity. During copulation, the concentration of DA in the MPOA was significantly increased. A significant difference was detected in changes of DA between copulators and non-copulators. These findings were consistent with the assertion that DA neuron activity in the MPOA facilities male copulatory behavior.

RESTORATION OF SEXUAL BEHAVIOR AND DOPAMINERGIC NEUROTRANSMISSION BY LONG TERM EXOGENOUS TESTOSTERONE REPLACEMENT IN AGED MALE RATS

PURPOSE We investigated the effects of long-term testosterone replacement on copulatory behavior and dopaminergic neurotransmission in the medial preoptic area of aged male rats. MATERIALS AND METHODS The rats were divided into 3 groups depending on testosterone replacement. Those in the long-term replacement group were castrated at the age of 12 months and received testosterone replacement thereafter for 12 months. In the short-term replacement group, rats were castrated at the age of 22 months and high or low dose testosterone replacement was done for 2 months. The control group consisted of aged rats 24 months old and young rats 12 weeks old, neither of which had been castrated or received testosterone replacement. We observed sexual behavior in rats of these groups. After a behavioral test, we measured the tissue concentration of dopamine in the MPOA and the change rate of the extracellular dopamine level induced by infusion of N-methyl-D-aspartic acid (NMDA) in the MPOA and compared the long-term replacement and no-replacement groups. RESULTS The rats in the long-term replacement group showed a mount rate at the same level as that of young rats at 6 weeks after starting replacement and it was maintained to 24 months of age. Their mount rate was significantly higher than that of the rats with the short-term replacement. A significantly higher change rate of dopamine release was recognized in the long-term group; however, no significant difference in the concentration of dopamine was recognized between aged rats with long-term replacement and those without replacement. CONCLUSIONS Aged rats (24 months old) with long-term testosterone replacement maintained almost the same level of mount behavior as young rats (12 weeks old). The results imply that long-term testosterone replacement may favorably alter the decline in the process of sexual activity with aging. The restoration by testosterone replacement of dopaminergic activity in the MPOA may be involved in the maintenance of sexual function in aged rats.

The Efficacy and Safety of Propiverine Hydrochloride in Patients with Overactive Bladder Symptoms Who Poorly Responded to Previous Anticholinergic Agents

Objectives. To prospectively examine the efficacy and safety of propiverine hydrochloride in patients with overactive bladder (OAB) symptoms who poorly responded to previous treatment with solifenacin, tolterodine or imidafenacin. Methods. Patients aged ≥20 with persisting OAB symptoms (≥6 in OAB symptom score (OABSS)) even after at least 4-week treatment using solifenacin, tolterodine or imidafenacin were enrolled. Propiverine 20 mg/day was administered for 12 weeks to 70 patients who desired the further improvement of OAB symptoms and 3 who had intolerable adverse events of previous drugs. The OABSS and postvoid residual urine volume (PVR) were determined before and at 4 and 12 weeks of treatment. Results. Of 73 patients enrolled (29 males and 44 females, median age 71 years), 52 completed the protocol treatment. The OABSS was significantly improved by propiverine treatment (9.0 at baseline, 6.2 at 4 weeks, 6.3 at 12 weeks (P < 0.001)). The scores of OAB symptoms (nighttime frequency, urgency and urge incontinence) except daytime frequency also improved significantly. No increase in PVR was observed. The most frequent adverse event was dry mouth (13.7%), followed by constipation (6.8%). Conclusions. Propiverine is useful to improve OAB for patients who poorly respond to solifenacin, tolterodine or imidafenacin.

Three-year outcome analysis of alpha 1-blocker naftopidil for patients with benign prostatic hyperplasia in a prospective multicenter study in Japan

Purpose Our aim was to prospectively analyze the 3-year outcomes of naftopidil treatment for patients with benign prostatic hyperplasia (BPH), including those who dropped out during follow-up and had retreatment for BPH after termination of the drug within 3 years. Patients and methods Naftopidil, 50 mg/d or 75 mg/d, was given to 117 patients having BPH aged 50 years and older who had international prostate symptom scores (IPSS) ≥8. They were prospectively followed for 3 years with periodic evaluation. If naftopidil was terminated, the reason was determined. For patients with termination, an outcome survey was done to evaluate the status of retreatment for BPH at 3 years. Results Twenty-five patients (21.4%) continued the same medication for 3 years. The total IPSS, quality of life index, BPH problem index, and maximum flow rate were significantly improved during 3 years. Treatment failure defined as symptomatic progression (an increase in the IPSS of ≥4 points compared to the baseline value), development of acute urinary retention, conversion to other α1-blockers, add-on of a 5α-reductase inhibitor, or conversion to surgery was observed in 41 patients (35.0%). In the univariate analysis, age, prostate volume, and serum prostate-specific antigen were predictors of treatment failure. Of the 50 patients who discontinued naftopidil during the follow-up, only 13 (26%) patients reported that they needed retreatment with α1-blockers and/or surgery within 3 years. Conclusion Long-term efficacy of naftopidil was observed, although older age, increased prostate volume, and elevated prostate-specific antigen at baseline were highly likely to result in treatment failure. Even after termination for various reasons, only a small portion of the patients needed retreatment for BPH within 3 years.

Significance of the combined treatment with isepamicin and piperacillin in an in vitro model for complicated cystitis operated by automatic simulator apparatus for urinary concentration

Isepamicin (ISP) and piperacillin (PIPC) were shifted to the urinary concentration by employing an in vitro complicated cystitis model operated by a computer-controlled automatic simulator for urinary concentration, and administrated to bacteria in the urinary bladder model (Pseudomonas aeruginosa: P. aeruginosa, initial cell concentration: 10(7) cfu/ml). In this case, effects by single treatment with ISP or PIPC on cell number curves were examined. Further, significance of the combined treatment with ISP and PIPC were investigated by changing the order of each treatment. And following the results were obtained. 1. In a single treatment with PIPC the cell concentration was minimum (10(4) cfu/ml) at 9th hour after its treatment and thereafter, regrowth to the same level as the initial concentration was observed at 16th hour. 2. In the case of single treatment with ISP, the cell concentration became minimum (10(2) cfu/ml) at 13th hour after the treatment and raised to the same concentration as the initial one at 25th hour. 3. In the combined treatment, the cell concentration was minimum (less than 10(1) cfu/ml) at 26th hour in the case of prior treatment with ISP. Thereafter, regrowth was observed and the cell concentration at 42nd hour reached to the initial cell concentration. 4. In simultaneous treatment with ISP and PIPC, the cell concentration at 24th hour was minimum (10(1) cfu/ml) and reached to the same level as the initial one after regrowth. From these results, it was found that the combined treatment with ISP and PIPC caused more reduction of the cell concentration than either single treatment. Further, regrowth of the cells was suppressed for longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)