To evaluate the etiology of erectile dysfunction: What should we know currently?

Erectile dysfunction (ED) is the inability to develop normal erection or an hardening problem at various extent that causes inability to maintain the erection for the sufficient time required for a complete sexual activity. It can be the result of neurologic, psychogenic, vascular, urogenital and hormonal abnormalities. It is reported that it affects 52-67% of men between 40 and 70 years old. Numerous theories and opinions are issued in the literature in order to explain the hemodynamic changea that occur during erection and detumescence. Especially the effects of chronic diseases and psychogenic factors on the pathophysiology of erectile dysfunction are common matters of discussion in recent years. In this review, we will evaluate the current developments in the literature about the etiology of erectile dysfunction.

Immunolocalization of glial cell-derived neurotrophic factor (GDNF) and its receptor GFR-alpha1 in varicocele-induced rat testis.

The aim of the study was to determine the immunolocalisation of glial cell-derived neurotrophic factor (GDNF) and its receptor (GFRalpha1) in testicular dysfunction induced by experimental left varicocele. Male Wistar rats were divided randomly into two groups: a varicocele-induced group and a sham-operated group for 9, 11 and 13 weeks (each group n=6). After orchiectomy, part of the left testis from each animal was fixed, processed and embedded in paraffin wax for immunohistochemistry and the other part was fixed for ultrastructural investigations. GDNF immunoreactivity was localized in the interstitial space in Leydig cell cytoplasm and there was no significant difference (P=0.5) between the varicocele-induced groups at the various time points. GFRalpha1 localization was perinuclear in spermatids and cytoplasmic in Leydig cells. The decrease of GFRalpha1 immunoreactivity was significant (P=0.001) in varicocele-induced testis at 13 weeks when compared with the age-matched sham group. This is the first study to describe the immunolocalization patterns of GDNF and GFRalpha1 in a rat model of varicocele. Although there was no change in GDNF labelling at the different time points after varicocele, GFRalpha1 was significantly decreased in the 13-week group. Distribution of GDNF and its receptor GFRalpha1 in normal and varicocele-induced rat testes suggests both autocrine and paracrine regulation of spermatogenesis.

Endoscopic treatment of ureteric strictures: acucise, cold-knife endoureterotomy and wall stents as a salvage approach.

OBJECTIVE: To evaluate the factors influencing the results of endoureterotomy using cold-knife and cutting balloon dilatation, and permanent ureteral wall stents in patients with benign ureteral strictures after different operations affecting the ureter. MATERIALS AND METHODS: Over a 4-year period, in 18 patients, endoscopic cold-knife and Acucise endoureterotomies were performed in 13 and 7 renal units, respectively. Eight Memoterm permanent ureteral wall stents were inserted into 7 patients when endoureterotomy failed. Successful outcome was defined by the absence of re-stricture assessed both clinically and radiologically. RESULTS: The strictures were secondary to ureterolithotomy in 6, ureteroscopy in 3, gynecological procedures in 4, abdominal surgeries in 2, transplantation in 2 and continent urinary diversion in 1. The right and left ureters were unilaterally affected in 5 and 11 patients, respectively (5 of them had a solitary kidney), while the remaining 2 patients had bilateral ureteral strictures. We achieved total ureteral patency of 3 (43%) and 7 (54%) renal units with Acucise and cold-knife incision, respectively. Obstructive uropathy was resolved in 6 renal units (75%) of 8 using ureteral wall stents. CONCLUSION: Endoureterotomy with cold-knife or Acucise cutting balloon dilatation is effective in the treatment of iatrogenic ureteral strictures, but only in a selected group. Based on our results, the favorable prognostic criteria for endoureterotomy are the length (< or =1.5 cm), the nonischemic nature of the stricture and adequate renal function. As a salvage approach, permanent self-expanding ureteral wall stents with a 75% success rate may provide a satisfactory outcome for decompression of an obstructed system.

The restorative effect of a selective cyclooxygenase-2 inhibitor on urothelial cell-cell interactions after partial bladder outlet obstruction in rats.

OBJECTIVE: To determine the changes in cyclooxygenase-2 (COX-2), E-cadherin and alpha-catenin expression after partial bladder outlet obstruction (PBOO), and whether a selective COX-2 inhibitor (celecoxib) might inhibit COX-2 expression and have beneficial effects on urothelial cell-to-cell interactions in rats subjected to PBOO. MATERIALS AND METHODS: Thirty-six male rats were divided into six equal groups; celecoxib was administered after creating PBOO for 1 and 4 weeks in groups 1 and 2, respectively. Two further obstructed groups (3 and 4, PBOO for 1 and 4 weeks, respectively) received no treatment. Sham-operated animals served as controls (group 5 and 6, assessed at 1 and 4 weeks, respectively). After 1 and 4 weeks of PBOO or a sham procedure the bladder weight was recorded before sampling the bladder for Western blotting and immunohistological analysis, to assess the expressions of COX-2 and adherens proteins, E-cadherin and alpha-catenin. Urothelial cell-to-cell interactions were evaluated using electron microscopy. RESULTS: The bladder mass increased rapidly during the first 7 days after PBOO in groups 1-4 compared with 5 and 6 (P < 0.05). While the bladder mass then continued to increase for the next 21 days in group 4, it was constant in group 2 (P < 0.001). Immunohistochemical staining and Western blotting analyses showed that E-cadherin and alpha-catenin expression were reversibly decreased in rats with PBOO, while COX-2 protein expression was up-regulated. After giving celecoxib there was a significant decrease in COX-2 expression and a restoration of intercellular adherens junctions and desmosomes, as assessed on electron microscopy and expression of adherens proteins combined. CONCLUSION: The increase in COX-2 expression attributable to hypoxia and the tensile strength of bladder wall was attenuated by celecoxib. Selective COX-2 inhibitors have important restorative effects on intercellular adherens junctions and desmosomes in PBOO.

Apoptotic and proliferative index after Alpha-1-adrenoceptor antagonist and/or finasteride treatment in benign prostatic hyperplasia.

INTRODUCTION: The induction of apoptosis has emerged as a potential target for optimization of the medical management of benign prostatic hyperplasia (BPH), recently. The influence of alpha1-adrenoceptor antagonist (alpha1-ARA), 5-alpha reductase inhibitor and their combination on prostatic cell apoptotic and proliferative indices of benign hyperplastic prostate gland were investigated. MATERIALS AND METHODS: A total of 49 male patients with BPH (mean age: 66.5 years) treated with alpha1-ARA and/or finasteride were retrospectively evaluated. Patients treated with alpha1-ARA (doxazosin n = 12 and terazosin n = 10), finasteride (n = 9) and combination of finasteride and alpha1-ARA (n = 9) were enrolled in the study. Primary antibodies were Ki-67 and proliferating cell nuclear antigen for the evaluation of proliferation in prostate stromal and epithelial cells. In situ apoptotic DNA fragmentation was evaluated using TUNEL assay. RESULTS: All treatment groups had no significant changes in the rate of prostate stromal and epithelial cell proliferation. Epithelial apoptotic index (AI) was not statistically significant for finasteride vs. alpha1- ARA, alpha1-ARA vs. finasteride + alpha1-ARA and finasteride + alpha1-ARA vs. finasteride groups. While alpha1-ARA was more effective than finasteride on stromal apoptosis, alpha1-ARA-induced stromal apoptosis was not significantly different from alpha1-ARA plus finasteirde treatment. CONCLUSION: Not only androgen variabilities but also alterations in sympathetic neurotransmission with age could have important implications for pathophysiological prostate growth. The combination of finasteride and alpha1-ARA is not superior to alpha1-ARA therapy with their similar epithelial and stromal apoptotic effects with unaffected cell proliferation.

Evaluation of penile hemodynamic status and adjustment of treatment alternatives in Peyronie's disease.

AIM: Erectile dysfunction may be observed in up to 80% of patients with Peyronie's disease. An objective evaluation of the erectile function is attempted to work out in patients with Peyronie's disease. METHODS: Penile deformity, sexual function and penile vascular status were analyzed in 123 patients with Peyronie's disease, who had not received any pertinent treatment. RESULTS: Penile deformity, palpable plaque and pain on erection were seen in 112 (91%), 97 (78.8%) and 27 (21.9%) of the 123 patients, respectively. Of the 76 patients evaluated by color Doppler ultrasounography, veno-occlusive dysfunction as the vascular component for erectile dysfunction was found in 17 (22.3%), arterial insufficiency in 10 (13.1%) and a mixed picture in 23 (30.2%). CONCLUSION: The documentation of penile erectile function and the determination of the vascular status using color Doppler ultrasonography can guide the appropriate therapeutic choice.

Is sildenafil citrate an alternative agent in the evaluation of penile vascular system with color Doppler ultrasound?

UNLABELLED: IINTRODUCION: The ideal diagnosis and therapeutic agent for erectile dysfunction (ED) would be an oral drug taken prior to color Doppler ultrasound (CDU) examination and sexual intercourse. In the present study we have investigated if the efficacy of oral sildenafil is optimal in the diagnosis of underlying pathology of ED. MATERIAL AND METHODS: The study group comprised of 41 patients with ED. Firstly, all patients underwent CDU examinations after the combined intracavernosal injection of 60 mg of papaverine and sexual stimulation (CIS). Secondly, these patients were examined after taking 50 mg of oral sildenafil citrate combined with self-manual and visual sexual stimulation. RERSULTS The differences of peak systolic velocity values were statistically significant between CIS and sildenafil (right: 40.7 +/- 2.9 vs. 28.7 +/- 3.3; left: 41.2 +/- 3.3 vs. 25.7 +/- 2.4; p < 0.001) in patients with normal penile vascular system. However, end-diastolic velocity and resistance index values were not significant between the same groups. In addition, there were not significant differences for peak systolic and end-diastolic blood flow velocities and resistances index with CIS and sildenafil in cases with vasculogenic ED. CONCLUSIONS: Sildenafil citrate plus visual sexual stimulation is not reliable as CIS to make accurate interpretation of penile vascular status using CDU. On the other hand, in some cases suspected of psychogenic ED after detailed sexual history, sildenafil might be tried as an initial step of the functional evaluation with CDU in order to prevent prolonged erection risk with intracavernosal injection of vasoactive agents.