Yasushi Nagase

Multidirectional contraction of human hypertrophied prostate.

1. The purpose of the present investigation is to evaluate muscle contraction in two directions (longitudinal and circumferential to urethra) physiologically and morphologically for alpha-adrenoceptor agonists. 2. Norepinephrine (10(-7)-10(-4) M), phenylephrine (10(-7)-10(-4) M) and clonidine (10(-7)-10(-4) M) induced contractions in a dose-dependent manner on human prostate from patients with benign prostatic hypertrophy (BPH). 3. No significant differences were observed between longitudinal and circumferential directions of human prostate in 50% of the maximal muscle contraction (EC50 values) and the maximal muscle contractions caused by any agents used. 4. Morphometric analysis for muscle in prostates was performed using formalin-fixed, paraffin-embedded sections stained by the Mallory-Azan method. 5. There was no significant difference in the density of the muscle area between longitudinal and circumferential directions of prostatic strips. 6. These results suggest that there are no significant differences in responsiveness of alpha-adrenoceptor agonists and the smooth muscle contents in longitudinal and circumferential directions to urethra, for human hypertrophied prostate.

Age-related changes in alpha1-adrenoceptors in rat prostate

The age-related changes in the density of alpha1-adrenoceptors in the dorsolateral lobe of the rat prostate were evaluated in Wistar rats at 8, 52, and 104 weeks of age. [3H]YM617, a newly senthesized alpha1-adrenergic blocker, was used as the ligand. The mean maximum number of binding sites, or alpha1-adrenoceptor density (Bmax)±SE of 104-week-old rats (11.0±1.2 fmol/mg protein) was significantly lower than that in the 8-week-old rats (37.0±4.3 fmol/mg protein) and 52-week-old rats (37.2±3.4 fmol/mg protein) respectively, P<0.01. In contrast, mean affinity (Kd) values±SE of these groups showed no significant differences (8-week-old rats, 115.8±9.1; 52-week-old rats, 100.5±5.8; and 104-week-old rats, 116.4±9.8 pM). Mean volumes±SE of muscle cells of the prostate were 3.7±1.1x103 μm3 at 8 weeks, 30.0±6.2x103 μm3 at 52 weeks, and 18.6±8.2x103 μm3 at 104 weeks. Volumes for 8-week-old rats were significantly smaller than those for 52-week-old (P<0.01) and 104-week-old rats (P<0.05). However, the mean area density of the muscle cells showed no difference among the three groups: 20.1±2.2% at 8 weeks, 27.3±2.9% at 52 weeks and 20.3±3.4% at 104 weeks. In conclusion, the density of YM617-binding sites (alpha1-adrenoceptors) in 104-week-old rats was lower than in 8- and 52-week-old rats. Muscle volume in the rat prostate was larger in rats aged 52 and 104 weeks than in 8-week-old rats, but no correlation was found between alpha1-adrenoceptor density and the muscle volume or muscle density in aging.

METASTATIC SMALL CELL CARCINOMA OF THE URINARY BLADDER TREATED WITH SYSTEMIC CHEMOTHERAPY INCLUDING AN AMRUBICIN; A CASE REPORT

We report a 59-year-old male patient with metastatic small cell carcinoma of the bladder treated with systemic chemotherapy including an amrubicin. The patient was referred to our hospital complaining of macrohematuria. A cytoscopy revealed a non-papillary, broad-based tumor extending from the right to the posterior wall of the bladder. A computed tomography showed bilateral hydronephrosis caused by the bladder tumor and multiple metastases to the para-aortic and common iliac lymph nodes. The histopathological findings following a transurethral resection of the bladder tumor revealed a T2N3M1, LYM, stage IV small cell carcinoma. We administered two courses of systemic chemotherapy consisting of cisplatin (CDDP) plus an etoposide (VP-16), a first-line treatment usually administered to patients with small cell carcinoma of the lung. We then administered second-line chemotherapy consisting of CDDP plus an irinotecan. When the first and second-line therapies failed to halt progression of the disease, we decided to use amrubicin as the third-line therapy concomitant with radiotherapy for local control. Although the NSE (neuron-specific enolase) value decreased, the patient died 11 months after the initial examination. To our knowledge, this is the first case in which small cell carcinoma of the bladder was treated with amrubicin.