[Therapeutic effect of tadalafil on lower urinary tract symptoms with erectile dysfunction].

OBJECTIVE: To investigate the therapeutic effect of low-dose tadalafil on BPH-induced lower urinary tract symptoms (LUTS) complicated with ED. METHODS: We randomly assigned 126 patients with BPH-induced LUTS and ED to receive daily administration of tadalafil (5 mg) plus tamsulosin hydrochloride sustained-release capsules (0.2 mg) (treatment group Ⅰ ［T-Ⅰ］, n = 42), tadalafil (5 mg) only (treatment group Ⅱ ［T-Ⅱ］, n = 42) or placebo (control group, n = 42), all for 12 weeks. Before and after 6 and 12 weeks of medication, and at 4 and 8 weeks after drug withdrawal, we recorded and compared the IPSS sub-item scores in the voiding stage and urinary storage symptoms, total IPSS, IIEF-5 scores, and the frequency of sexual activities among the three groups of patients. RESULTS: As for the IPSS sub-item scores in the voiding stage symptoms, T-Ⅰ showed statistically significant differences between any two of the five time points (P < 0.05), but not T-Ⅱ between the baseline and 6-week medication or 8-week withdrawal (P > 0.05), or between 6-week medication and 8-week withdrawal (P > 0.05), nor did the control group among the five time points (P > 0.05). Statistically significant differences were observed between any two of the three groups at 12 weeks of medication and 4 weeks after drug withdrawal (P < 0.05), but not between the T-Ⅱ and control groups at 6 weeks of medication or 8 weeks after withdrawal (P > 0.05). As to the IPSS sub-item scores in the urinary storage symptoms, there were significant differences between any two time points in T-Ⅰ and T-Ⅱ (P < 0.05), but not in the control (P > 0.05), nor between T-Ⅰ and T-Ⅱ at 6 or 12 weeks of medication or at 4 or 8 weeks after drug withdrawal (P > 0.05). With regard to the total IPSS, statistically significant differences were found between any two of the three groups at 6 and 12 weeks of medication and 4 and 8 weeks after drug withdrawal (P < 0.05), but not between 6-week medication and 8-week withdrawal in T-Ⅰ or T-Ⅱ (P > 0.05), nor among the five time points in the control group (P > 0.05). Concerning the IIEF-5 scores, there was no significant difference in the frequency of sexual activities between the three groups （Ｐ>0.05）.There were statistically significant differences between any two of the three groups at 6 weeks of medication and 8 weeks after drug withdrawal (Ｐ<0.05), but not between 6-week medication and 4- or 8-week withdrawal (P > 0.05) or between 4- and 8-week withdrawal (P > 0.05) in T-Ⅰ, nor between 6-week medication and 8-week withdrawal in T-Ⅱ (P > 0.05) or among the five time points in the control (P > 0.05), nor between T-Ⅰ and T-Ⅱ at 12 weeks of medication (P > 0.05) or 4 weeks after drug withdrawal (P > 0.05). CONCLUSIONS: Daily administration of tadalafil at 5 mg can effectively improve the IPSS sub-item scores in the urinary storage symptoms and IIEF-5 scores, with a persistent effect after withdrawal similar to that of its combination with other drugs, and therefore can be recommended for the treatment of BPH-induced LUTS complicated with ED.

LncRNA THOR promotes human renal cell carcinoma cell growth.

BACKGROUND: Recent studies have characterized a novel but extremely conserved long non-coding RNA (LncRNA) THOR. THOR directly associates with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to promote mRNA stabilization of key pro-cancerous genes. RESULTS: Here, we show that THOR is expressed in human renal cell carcinoma (RCC) tissues and established/primary human RCC cells. It was not detected in normal renal tissues nor in HK-2 and primary human renal epithelial cells. THOR silencing (by targeted siRNAs) or CRISPR/Cas9 knockout inhibited RCC cell growth, viability and proliferation in vitro. Reversely, forced over-expression of THOR promoted RCC cell survival and proliferation. IGF2BP1-regulated genes, including IGF2, GLI1 and Myc, were downregulated by THOR silencing or knockout, but they were upregulated after THOR over-expression. In vivo, THOR-knockout 786-O tumors grew significantly slower than the control tumors in nude mice. CONCLUSION: THOR expression promotes RCC cell growth in vitro and in vivo. THOR could be a novel and important therapeutic target for human RCC.

[Effects of sildenafil on bladder compliance and endothelin-1 in rabbit model of partial bladder outlet obstruction].

OBJECTIVE: To explore the effects of sildenafil on bladder compliance and endothelin-1 in the rabbit model of partial bladder outlet obstruction. METHODS: A total of 24 adult male New Zealand white rabbits were randomly divided into group A, group B, group C and group D (n = 6 each). The rabbit model of partial bladder outlet obstruction was established in groups C and D while groups A and B underwent a sham operation. Daily sildenafil (10 mg/kg) was dosed to groups B and C by lavage. Daily normal saline was dosed similarly to groups A and D. Bladder urodynamic examinations were conducted in each group at Week 16. Then bladder was isolated and weighed from each group. And ET-1 in bladder tissue was measured by ELISA. RESULTS: Pressure thresholds for voiding (PT) in A-D groups were (10.6 ± 2.0), (11.6 ± 2.7), (14.0 ± 4.2) and (20.4 ± 6.1) cm H2O respectively. Compared with groups A, B and C, PT in group D was significantly higher (all P < 0.01). Bladder compliance in 4 groups were (2.75 ± 0.51), (2.78 ± 0.46), (4.98 ± 2.15) and (1.22 ± 0.25) ml/cm H2O respectively. Compared with groups A, B and C, bladder compliance was significantly lower in group D (all P < 0.01). Bladder compliance in group C was higher than that in groups A and B (both P < 0.01). The weights of bladder specimens in 4 groups were (5.0 ± 0.4), (4.6 ± 0.4), (8.2 ± 1.3) and (17.9 ± 2.3) g respectively. Compared with groups A and B, the weights of groups C and D were significantly heavier (all P < 0.01). And the weight of group D was much greater than that of group C (P < 0.01). The contents of ET-1 in bladder tissue of 4 groups were (72 ± 19), (69 ± 18), (76 ± 21) and (106 ± 29) pg/g respectively. Compared with groups A, B and C, ET-1 in bladder tissue was significantly higher in group D (all P < 0.05). CONCLUSIONS: Daily sildenafil can effectively alleviate the damage of rabbit bladder compliance from partial bladder outlet obstruction and protect bladder functions. Its mechanism may be related with the down-regulation of ET-1 in bladder tissue of partial bladder outlet obstruction.

[Effects and mechanisms of phosphodiesterase type 5 inhibitors on rats with overactive bladder].

OBJECTIVE: To investigate the effects and the possible mechanistic pathway of phosphodiesterase type 5 (PDE5) inhibitors on rats with overactive bladder. METHODS: A total of 24 adult male spontaneously hypertensive rats (SHRs) were randomly divided into 3 groups: daily lavage group, discontinuous lavage group and blank group (n = 8 each). Daily vardenafil (10 mg×kg(-1)×d(-1)), discontinuous vardenafil (10 mg×kg(-1)×d(-1)) and daily normal saline were administered respectively to 3 groups by lavage. And 8 adult male SD rats were included into the control group. Bladder urodynamic examinations were conducted in each group 2 weeks later. Then bladder detrusor muscle strips isolated from each group were further divided into two parts. One part was first pre-contracted and then the relaxant effects of sodium nitroprusside and Y-27632 were observed. For another part, enzyme-linked immunosorbent assay was used to measure cyclic guanosine monophosphate (cGMP). RESULTS: As compared with the control group, the values of bladder inter contraction interval (ICI) and bladder capacity (BC) were significantly lower [(409 ± 36) s vs (568 ± 60) s, (284 ± 25) µl vs (395 ± 42) µl, P < 0.01] while the bladder non voiding contraction (NVC) was significantly higher in the blank group [(2.03 ± 0.49) number/min vs(1.07 ± 0.30) number/min, P < 0.01]. Compared with the blank group, the values of ICI and BC were elevated. NVC decreased obviously in the discontinues and daily lavage groups [(486 ± 53) s and (564 ± 44) s; (337 ± 37) µl and (392 ± 30) µl; (1.82 ± 0.32) number/min and (0.52 ± 0.23) number/min, P < 0.05]. The effects were more significant in the daily lavage group (P < 0.01). The maximal relaxant effect of sodium nitroprusside was obviously enhanced in the discontinues and daily lavage groups [(50.6 ± 2.1)% and (67.9 ± 4.1)% vs(25.3 ± 5.0)%, P < 0.01]. However the sensitivity of Y-27632 decreased significantly [(35.8 ± 2.5)% and (20.2 ± 2.3)% vs (71.6 ± 2.8)%, P < 0.01], while the level of cGMP was significantly higher in the bladder detrusor muscle [(20.6 ± 4.1) fmol/mg and (29.4 ± 4.3) fmol/mg vs (12.9 ± 2.1) fmol/mg, P < 0.01]. The effects of the daily lavage group were more pronounced (P < 0.01). CONCLUSION: The phenomenon of bladder overactivity is observed in the SHRs. The PDE5 inhibitors are effective in treating overactive bladder. And the effect of daily supplement is much better. In addition, the mechanism may operate through the cGMP-dependent protein kinase G-RhoA/Rho kinase signaling pathway.

Efficacy of daily low-dose sildenafil for treating interstitial cystitis: results of a randomized, double-blind, placebo-controlled trial--treatment of interstitial cystitis/painful bladder syndrome with low-dose sildenafil.

OBJECTIVE: To evaluate the efficacy of daily low-dose sildenafil for the treatment of nonulcer interstitial cystitis (IC) in women. PATIENTS AND METHODS: Forty-eight women with a clinical diagnosis of IC from 3 medical centers were randomly assigned to treatment with daily low-dose sildenafil (25 mg, n=24) or placebo (n=24) for 3 months. The O'Leary-Sant IC symptom and problem indices, visual analog scale scores, and a micturition diary with the interval of micturition, the frequency of nocturia, and urgency episodes were recorded before treatment, every 2 weeks after the treatment until 3 months. Patient Overall Rating of Improvement in Symptoms was assessed and regarded as effective when the value was above 50%. RESULTS: The IC symptom and problem indices scores and urodynamic index were significantly improved in sildenafil treatment group as compared with placebo group and baselines at week 4, 6, 8, 10, and 12, as well as 3 months after treatment (P<.05). Urodynamic index including first desire to void, strong desire to void, and maximum cystometric capacity was significantly improved in sildenafil treatment group at week 12 and at 3 months after treatment (P<.05). The efficiency of treatment reached 62.5%. However, no significant change of the visual analog scale values was observed between 2 groups except at week 12 in the sildenafil treatment group (P<.05). All adverse events were mild to moderate and transient. CONCLUSION: Daily low-dose sildenafil is an easy, well-tolerated, and effective treatment for IC in women.