Tadashi Hanai

Effects of Tamsulosin on Bladder Blood Flow and Bladder Function in Rats With Bladder Outlet Obstruction

OBJECTIVES To investigate the mechanism underlying the ameliorating effect of tamsulosin, an alpha(1)-adrenoceptor antagonist, on storage symptoms associated with benign prostatic hyperplasia, the effects of tamsulosin on bladder blood flow (BBF) and bladder function was evaluated in rats with bladder outlet obstruction (BOO). METHODS BOO was produced by partial ligature of the proximal urethra, which was maintained for 2 weeks. Tamsulosin was subcutaneously administered via an osmotic pump for 2 weeks immediately after the BOO surgery. The BBF in the sham-operated rats, the control BOO rats, and the tamsulosin-treated BOO rats was measured using the fluoromicrosphere method. Each rat was kept in a metabolic cage for observation of micturition behavior. Expression of the alpha(1)-adrenoceptor subtype mRNA in the vesical artery was measured by reverse transcriptase-polymerase chain reaction. RESULTS BBF was significantly reduced in BOO rats compared with sham-operated rats, and tamsulosin significantly increased the BBF in BOO rats. Tamsulosin ameliorated the decrease in mean voided volume in BOO rats with bladder masses < 500 mg. Expression of the alpha(1)-adrenoceptor subtype in the vesical artery was alpha(1a)- > alpha(1d)-adrenoceptors; almost no expression was observed of alpha(1b)-adrenoceptors in either sham-operated or BOO rats. CONCLUSIONS Tamsulosin increased BBF in BOO rats via an antagonistic effect, presumably on the alpha(1A)- and/or alpha(1D)-adrenoceptor in the vesical artery mainly, and improved the decrease in mean voided volume. Therefore, the results of this study suggest that tamsulosin improves bladder overactivity via improvement of BBF.

Bladder smooth muscle cell phenotypic changes and implication of expression of contractile proteins (especially caldesmon) in rats after partial outlet obstruction

Background: The purpose of the present study was to investigate morphological changes in bladder smooth muscle of rats with partial outlet obstruction. We investigated smooth muscle cell phenotypic changes and implication of synthetic phenotype in contractility decrease and bladder compliance after bladder outlet obstruction.

Eviprostat suppresses urinary oxidative stress in a rabbit model of partial bladder outlet obstruction and in patients with benign prostatic hyperplasia.

Eviprostat is a phytotherapeutic agent that has been used widely for more than 40 years in the treatment of benign prostatic hyperplasia (BPH) in Japan and Germany, and is known to have antioxidant activity. The present study investigated the effect of Eviprostat on the levels of the urinary oxidative stress marker 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) in a rabbit model of surgical partial bladder outlet obstruction (PBOO) and in patients with lower urinary tract symptoms (LUTS) associated with BPH. In the rabbit model, 8‐OHdG levels in urine collected after 3 weeks of PBOO were 3.8‐fold higher than in the urine of sham‐operated rabbits. When twice‐daily Eviprostat was administered orally throughout the 3‐week PBOO period, the increase in urinary 8‐OHdG levels was suppressed by 70%. In the clinical study, nine patients who received Eviprostat for 4 weeks showed 2.5‐fold lower urinary 8‐OHdG levels than before treatment. During Eviprostat treatment, the total International Prostate Symptom Score (IPSS) decreased from 16.56 ± 2.74 to 13.67 ± 2.30 and the quality of life score from 4.22 ± 0.40 to 3.22 ± 0.46. The findings provide evidence that the antioxidant activity of Eviprostat is responsible for its beneficial effects in the treatment of BPH. Copyright

Effects of chronic treatment with vardenafil, a phosphodiesterase 5 inhibitor, on female rat bladder in a partial bladder outlet obstruction model

To investigate whether vardenafil, a phosphodiesterase 5 (PDE‐5) inhibitor, would protect the bladder from decompensatory changes in a 4‐week rat bladder outlet obstruction (BOO) model, as evidence has been accumulating that PDE‐5 inhibitors improve lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).

Long-term outcome of the endoscopic correction of vesico-ureteric reflux: a comparison of injected substances.

To summarize the long‐term outcome of endoscopic surgery to correct vesico‐ureteric reflux (VUR) using different injected substances, i.e. autologous blood, hyaluronan/dextranomer copolymer (HDC), PTFE and glutaraldehyde cross‐linked bovine dermal (GAX) collagen.

Partial outlet obstruction of the rat bladder induces a stimulatory response on proliferation of the bladder smooth muscle cells.

Outlet obstruction of the ratbladder induces hypertrophy/hyperplasiacharacterized by increases in bladder mass,smooth muscle content, and collagen deposition.In order to understand the mechanism of theoutlet obstruction-induced hypertrophy andhyperplasia, we first determined the temporalpattern of changes in bladder mass afterinducing the outlet obstruction. Histologicalanalysis revealed that the smooth muscle cellswith hypertrophy and hyperplasia, fibroblastsand connective tissue were increased in atime-dependent manner, corresponding to thetemporal pattern observed in the changes inbladder mass, although the phase of changes inthese tissue components was somewhat different.In order to further determine whether anyproliferation-stimulatory factors were releasedfrom the bladder with obstruction incorrespondence with increased bladder mass,soluble fractions were prepared from thebladders with outlet obstruction for 3–30weeks, and their effects on proliferation ofsmooth muscle cells were examined. The solublefractions prepared from the bladders at 3 to 14weeks after obstruction slightly butsignificantly facilitated the proliferation ofcultured smooth muscle cells, while the solublefractions released after 20 weeks rathersuppressed the proliferation. These resultssuggest that the initial increase in bladdermass might be in part due to the facilitatedproliferation of smooth muscle cells of thebladder body induced by growth factors releasedinto the soluble fractions, and thathypertrophy might then play a role in theincreased bladder mass at later phases.

Bladder outlet obstruction accelerates bladder carcinogenesis

To examine the correlation between partial bladder outlet obstruction (PBOO) and bladder carcinogenesis.

Why is transurethral microwave thermotherapy (TUMT) positively effective

Between 1992 and 1994, 157 patients with benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). In evaluating the efficacy of TUMT with the International Prostate Symptom Score (I-PSS) in 121 patients, 18 (15%) showed excellent and 42 (35%) showed good response. In evaluation of QOL, the result was 43 patients (33%) excellent and 42 patients (35%) good response. In objective evaluation of uroflow in 93 patients, 12 (13%) showed excellent and 13 (14%) showed good response. The prostatic volume did not show a significant decrease after treatment. In terms of overall improvement, according to the criteria proposed at the 2nd International Consultation on BPH, the treatment was considered effective in 53 of 108 patients (48%). Histological examination of the prostate enucleated from a patient 7 months after TUMT revealed degenerative changes of nerve fibres on S-100 protein immunohistochemical staining, which were more extensive than those in smooth muscle cells on HE staining. Inin vitro tests the isometric contraction force of the rabbit prostatic tissue was measured after exposure to different temperatures, ranging from 37 to 50 °C. No significant change was observed up to 45°C vs. 37°C. After exposure to 48°C, the nerve mediated contractions became completely depressed, although phenylephrine or KCl induced contractions were only partially suppressed. After exposure to 50°C, no contraction was induced by any type of stimuli. In conclusion, it is suggested that good symptomatic improvement after TUMT results from both neural and muscular damage to the prostate. As TUMT is not aiming at a relief of anatomical obstruction, 50°C is thought to be a sufficient thermal condition to cause an irreversible damage to prostatic tissue, which will provide a relief from functional obstruction and urethral instability.

Medial prefrontal cortex lesions inhibit reflex micturition in anethetized rats

The medial prefrontal cortex is thought to participate in the control of micturition and urinary continence, based on evidence from clinical reports, but its exact role is not fully understood. This study investigated whether ibotenic acid lesions of the medial prefrontal cortex would influence volume-evoked micturition in urethane-anesthetized rats. The incidence and amplitude of bladder contractions were recorded during continuous saline infusion (0.1 ml/min) immediately before and 1 week after ibotenic acid (0.5 microg) or vehicle (0.5 microl) was injected into the medial prefrontal cortex. Vehicle injection did not change the incidence or amplitude of bladder contractions compared to pre-injection values. Ibotenic acid lesions prolonged the time interval between bladder contractions significantly although it did not affect the amplitude of bladder contractions. Histological analysis revealed that ibotenic acid lesions were restricted primarily to the anterior cingulate and prelimbic cortices. Larger ibotenic acid lesions extending ventrally into the infralimbic cortex produced a variable response but did not change the overall incidence or amplitude of bladder contractions significantly. These data indicate that the medial prefrontal cortex influences the timing of bladder contractions but does not affect contraction amplitudes.

Postrenal acute renal failure during pregnancy 20 years after antireflux surgery

We report that a 27-year-old woman withbilateral severe hydronephorosis duringpregnancy 20 years after antireflux surgery. The patient developed postrenal acute renalfailure due to obstruction of the lower ureter. This patient could safely give birth afterbilateral percutaneous nephrostomy throughjoint management with the obstetrics andgynecology staff. We describe that stenosis ofthe lower ureter is a late complication ofantireflux surgery.