Effect of co-administration of BRL-37344 and tadalafil on reduction of overactive bladder symptoms after induction of detrusor overactivity in mice

Abstract Purpose: To evaluate the impact of the combination of BRL 37344 and tadalafil (TDF) on the reduction of overactive bladder (OB) symptoms. Methods: Thirty mice were randomized into 5 groups (G) of 6 animals each. L-NAME was used to induce DO. G1: Control; G2: L-NAME; G3: L-NAME + TDF; G4: L-NAME + BRL 37344; G5: L-NAME + TDF + BRL 37344. After 30 days of treatment, the animals were submitted to cystometry to evaluate non-voiding contractions (NVC), threshold pressure (TP), baseline pressure (BP), frequency of micturition (FM) and threshold volume (TV). Differences between the groups were analyzed with ANOVA followed by the Tukey test. Results: NVC increased in G2 (4.33±2.58) in relation to G1 (1.50±0.55). NVC decreased in G3 (2.00±1.10), G4 (1.50±1.52) and G5 (2.00±1.26) compared to G2 (p<0.05). FM decreased in G3 (0.97±0.71), G4 (0.92±0.38) and G5 (1.05±0.44) compared to G2 (p<0.05). However, the combination of TDF and BRL37344 was not more effective at increasing NVC and improving FM than either drug alone. The five groups did not differ significantly with regard to TV. Conclusion: The combination of BRL 37344 and TDF produced no measurable additive effect on reduction of OB symptoms.

Impact of testicular sperm extraction and testicular sperm aspiration on gonadal function in an experimental rat model

ABSTRACT Purpose To assess the impact of sperm retrieval on the gonadal function of rats with impaired spermatogenesis by comparing testicular sperm extraction (TESE) to aspiration (TESA). The efficacy of these procedures to sperm obtainment was also compared. Materials and Methods A pilot study showed impaired spermatogenesis, but normal testosterone (T) production after a bilateral orchidopexy applied to 26 rats, which were randomly assigned into four groups: TESE (n=7), TESA (n=7), SHAM (n=6) and Control (n=6). The T levels were measured through comparative analysis after the orchidopexy. Results There was no statistical difference in the animal's baseline T levels after orchidopexy in comparison to the controls: the TESE and TESA groups, 6.66±4.67ng/mL; the SHAM group (orchidopexy only), 4.99±1.96ng/mL; and the Control, 4.75±1.45ng/mL, p=0.27. Accordingly, no difference was found in the postoperative T levels: TESE, 5.35±4.65ng/mL; TESA, 3.96±0.80ng/mL; SHAM, 3.70±1.27ng/mL; p=0.4. The number of sperm cells found through TESE (41.0±7.0) was significantly larger than that found through TESA (21.3±8.1, p=0.001). Moreover, higher tissue weight was found through TESE (0.09±0.02g versus 0.04±0.04g, p=0.04). Conclusions The testicular sperm capture performed in rats through extraction or aspiration, after orchidopexy, did not significantly decrease the T levels. The amount of sperm found through testicular sperm extraction was higher than that through testicular sperm aspiration.

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

Purpose The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Materials and Methods Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. Results The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. Conclusion In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles. .

Locally advanced penile carcinoma: classic emasculation or testis-sparing surgery?

The study evaluates the clinical and pathological findings of 16 patients with locally advanced penile carcinoma (PC) submitted to emasculation, and discusses questions related to the usefulness of bilateral orchiectomy.

Between 1999 and 2010, 172 patients with PC were treated. Sixteen (9%) underwent emasculation. Data were retrieved from the institution's database including age, ethnicity, date of surgery, residential setting, level of schooling, time to diagnosis, type of reconstruction, complications, tumor stage and grade, vascular and perineural invasion along with invasion of corpus cavernosum, corpus spongiosum, testicles, scrotum and urethra.

A total of 16 patients (average: 63.1 years) with locally advanced PC were included. All were illiterate or semiliterate rural dwellers and 87% were white. The time to diagnosis was 8-12 months. The mean follow-up time was 31.9 months (1-119). By the time of the last follow-up, only seven patients (43.75%) were alive. Tumors were pT4 (n = 6), pT3 (n = 8), pT2 (n = 2), Grade I (n = 5) and Grade II (n = 11). The histopathological examination revealed invasion of the urethra (n = 13), scrotum (n = 5) and testicles (n = 1). The surgical margin was positive in one patient. Six patients (37.5%) had vascular invasion and 11 (68.7%) had perineural invasion. Currently, only one of the former is alive.

The finding of focal microscopic testicular infiltration in only one of 32 testicles, even in the presence of clinically apparent scrotal invasion, suggests that emasculation without bilateral orchiectomy is a safe treatment option for patients with locally advanced PC. .

Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle by a new nitric oxide donor ruthenium compound

PURPOSE: The aim of this study was to evaluate the relaxation in vitro of cavernous smooth muscle induced by a new NO donor of the complex nitrosil-ruthenium, named trans-[Ru(NH3)4(caffeine)(NO)]C13 (Rut-Caf) and sodium nitroprusside (SNP). MATERIALS AND METHODS: The tissues, immersed in isolated bath systems, were pre-contracted with phenilephrine (PE) (1 µM) and then concentration-response curves (10-12 - 10-4 M) were obtained. To clarify the mechanism of action involved, it was added to the baths ODQ (10 µM, 30 µM), oxyhemoglobin (10 µM), L-cysteine (100 µM), hydroxicobalamine (100 µM), glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid nitrogen to measure the amount of cGMP and cAMP produced. RESULTS: The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC50) and maximum effect (Emax). The substances showed activity through activation of the soluble guanylyl cyclase (sGC), because the relaxations were inhibited by ODQ. Oxyhemoglobin significantly diminished the relaxation effect of the substances. L-cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine significantly diminished the relaxation effect of Rut-Caf. Glibenclamide significantly increased the efficacy of Rut-Caf (pEC50 4.09 x 7.09). There were no alterations of potency or maximum effect of the substances with the addition of the other ion channel blockers. Rut-Caf induced production of significant amounts of cGMP and cAMP during the relaxation process. CONCLUSIONS: In conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by means of activation of sGC with intracellular production of cGMP and cAMP; and also by release of NO in the intracellular environment. Rut-Caf releases the NO free radical and it does not act directly on the potassium ion channels.