Sickle cell disease (SCD)-associated priapism is characterized by decreased nitric oxide (NO) signaling and downregulated phosphodiesterase (PDE)5 protein expression and activity in the penis. Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the penis in SCD are not known. Given the critical role of androgens in erection physiology and NO synthase (NOS)/PDE5 expression, we hypothesized that testosterone replacement to eugonadal testosterone levels reduces priapism by reversing impaired endothelial (e)NOS activity and molecular abnormalities involving PDE5. Adult male transgenic Berkeley sickle cell (Sickle) and wild-type (WT) mice were implanted with testosterone pellets, which release 1.2 μg testosterone/day for 21 days, or vehicle. After 21 days, animals underwent erectile function assessment followed by collection of blood for serum testosterone measurements, penes for molecular analysis, and seminal vesicles as testosterone-responsive tissue. Serum testosterone levels were measured by radioimmunoassay; protein expressions of PDE5, α-smooth muscle actin, eNOS and nNOS, and phosphorylation of PDE5 at Ser-92, eNOS at Ser-1177, neuronal (n) NOS at Ser-1412, and Akt at Ser-473 were measured by Western blot in penile tissue. Testosterone treatment reversed downregulated serum testosterone levels and increased (p < 0.05) the weight of seminal vesicles in Sickle mice to levels comparable to that of WT mice, indicating restored testosterone levels in Sickle mice. Testosterone treatment reduced (p < 0.05) prolonged detumescence in Sickle mice and normalized downregulated P-PDE5 (Ser-92), PDE5, P-eNOS (Ser-1177), and P-Akt (Ser-473) protein expressions in the Sickle mouse penis. Testosterone treatment did not affect P-nNOS (Ser-1412), eNOS, nNOS, or α-smooth muscle actin protein expressions in the Sickle mouse penis. In conclusion, in the mouse model of human SCD, increasing testosterone to eugonadal levels reduced priapic activity and reversed impaired Akt/eNOS activity and PDE5 protein expression in the penis.
Aim: The objective of this study was to report the long-term outcomes and complications of patients with multiple sclerosis (MS) who underwent noncontinent urinary diversion to treat lower urinary tract symptoms (LUTS). Material and Methods: A retrospective study included all adult patients with MS who underwent an ileal conduit urinary diversion between 2000 and 2015.Early postoperative complications were reported as well as long-term complications, reoperation rates, and renal function.Results: Overall, 91 patients were included. The surgery was indicated for refractory urinary incontinence (n = 73), renal failure (n = 8), major perineal skin ulcer due to urinary incontinence (n = 6), and recurrent urinary tract infections (n = 4). The median follow-up was 50 months (range, 3-158 months). A significant reduction (P < .05) of postoperative nonobstructive pyelonephritis rate was observed. There was no significant difference between preoperative and postoperative renal function (P = .32). Early postoperative complications were reported in 24 patients (26%): 4 Clavien I, 6 Clavien II, 9 Clavien III, 4Clavien IV, and 1 Clavien V. Nine patients required reoperation for these complications (9.9%). Late complications were reported in 28 patients (30.8%): 8 ureteral anastomosis stenosis, 2 stoma stenosis, 2 incisional hernias, 6 kidney or ureteral lithiasis, and 10 pyelonephritis. Among them, 15 patients (16.5%) required reoperation for late complications.Conclusion: Noncontinent urinary diversion using ileal conduit appears to be an effective end-stage solution in MS patients. The perioperative morbidity rate of 26% and the late complication rate of 31% should be considered to better inform patients before the surgery. K E Y W O R D Scomplications, ileal conduit, multiple sclerosis, surgery, urinary diversion, urinary incontinence
Objectives To investigate detrusor function and cAMP activation as a possible target for detrusor overactivity in an experimental model lacking a key denitrosylation enzyme, S-nitrosoglutathione reductase (GSNOR). Materials and Methods GSNOR-deficient (GSNOR−/−) (n=30) and wild-type (WT) mice (n=26) were treated for 7 days with the cAMP activator, colforsin (1mg/kg), or vehicle intraperitoneally. Cystometric studies or molecular analyses of bladder specimens were performed. Bladder function indices and expression levels of proteins that regulate detrusor relaxation (nitric oxide synthase pathway) or contraction (RhoA/Rho-kinase pathway) and oxidative stress were assessed. Student t-test and one-way ANOVA were used. Results GSNOR−/− mice showed a significant increase (P<0.05) in voiding and non-voiding contraction frequencies compared to WT mice (Cohen’s effect size values d = 1.82 and 2.52, respectively). Colforsin normalized these abnormalities (Cohen’s effect size values d = 1.85 and 1.28, respectively). Western blot analyses showed an up-regulation of the RhoA/Rho-kinase pathway reflected by a significant increase (P<0.05) of phosphorylated-MYPT1 expression in GSNOR−/− mouse bladders, which was reversed by colforsin treatment. An increased level (P<0.05) of gp91phox expression in bladders of GSNOR−/− mice was observed without significant change after colforsin treatment. Neuronal and endothelial nitric oxide synthase phosphorylation on Ser-1412 and Ser-1177, respectively, did not differ between GSNOR−/− and WT mouse bladders irrespective of colforsin treatment. Conclusion Impaired denitrosylation is associated with detrusor overactivity that is linked with upregulated RhoA/Rho-kinase signaling. Colforsin reverses physiologic and molecular abnormalities. This study describes a novel model of detrusor overactivity and suggests a possible basis for its treatment.
Background Penile prothesis (PP) is the gold-standard treatment of drug-refractory erectile dysfunction (ED). While postoperative outcomes have been widely described in the literature, there are few data about patient satisfaction and intraoperative events. We aimed to assess long-term patient satisfaction and perioperative outcomes after PP implantation in a single-centre cohort of unselected patients using validated scales. Results A total of 130 patients received a PP (median age: 62.5 years [IQR: 58–69]; median International Index of Erectile Function (IEEF-5) score: 6 [IQR: 5–7]). Median follow-up was 6.3 years [IQR: 4–9.4]. Thirty-two (24.6%) patients underwent surgical revision, of which 20 were PP removals (15.4%). Global PP survival rate was 84.6% and previous PP placement was a risk factor for PP removal (p = 0.02). There were six (4.6%) non-life-threatening intraoperative events including two which resulted in non-placement of a PP (1.5%). EAUiaic grade was 0 for 124 procedures (95.4%), 1 for four procedures (3.1%) and 2 for two procedures (1.5%). Of patients who still had their PP at the end of the study, 91 (80.5%) expressed satisfaction. Conclusions PP implantation is a last-resort treatment for ED with a satisfactory outcome. PPs are well accepted by patients.
The aim of this article is to assess the outcomes of a low-intensity extracorporeal shock wave therapy (LiESWT) protocol for the treatment of Peyronie's disease (PD). Patients treated for PD were prospectively recorded, and data were retrospectively reviewed. Age, characteristics of fibrous plaques, concomitant treatments, International Index of Erectile Function (IIEF-5), Lue score, and pain score on Likert scale were collected. Patients in acute phase of PD and an angulation of <40° were included. The protocol consisted of 6 weekly sessions of 4000 pulses each, applied from different directions, with a maximal power of 20 W and 8 Hz frequency. We included 39 patients (median age: 56.8 years, interquartile range [IQR]: 35.8–62.2 years). The median number of sessions received per patient was 7.2. After treatment, the median Lue score decreased from 6.8 initially to 3.3 ( P = 0.003), the median Likert pain score dropped from 1.8 to 0.7 ( P = 0.004), the median plaque size was reduced from 2 cm to 1.2 cm ( P = 0.08), and the median penile curvature diminished from 31° to 17° ( P = 0.07). On univariate and multivariate analysis, the only predictors of success were younger age (odds ratio [OR] = 0.95, P = 0.03 and OR = 0.91, P = 0.04, respectively) and concomitant use of phosphodiesterase-5 inhibitors (PDE5i; OR = 0.92, P = 0.02 and OR = 0.93, P = 0.01, respectively). LiESWT had a favorable impact on Lue score and notably penile pain, curvature, plaque size, and erectile function in patients treated for PD during the early inflammatory phase, with no side effects. Younger age and concomitant use of PDE5i were the only success predictors.
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