Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats.

To evaluate the protective role of bosentan (BOS), an endothelin-1 (ET-1) receptor antagonist, and to show the changes in rats with experimentally induced diabetic erectile dysfunction (ED), a total of 24 albino Wistar rats were allocated into four groups. Group 1 was the healthy group and Group 2 had diabetes mellitus (DM) induced by intraperitoneal injection of 60 mg kg-1 streptozotocin (STZ). Following the establishment of DM, Group 3 and Group 4 were treated with oral BOS doses of 50 mg kg-1 and 100 mg kg-1 , respectively, for 60 days. At the end of the treatment, we evaluated yawning and erection response to apomorphine treatment and then the animals were sacrificed. ET-1, eNOS, iNOS, tumour necrosis factor (TNF)-α, ET-RA and ET-RB mRNA expressions were analysed in cavernosal tissue. It was observed that yawning and erection response decreased in the diabetic group; however, both of these improved with BOS treatment. While ET-1, TNF-α and iNOS gene expressions increased, eNOS, ET-RA and ET-RB gene expressions decreased in the DM group compared to the healthy group. DM has a negative impact on cavernosal tissue blood flow through activating vasoconstrictor mediators in cavernosal tissue. BOS regulates significantly eNOS, iNOS and TNF-α expressions in a dose-dependent manner.

Efficacy and tolerability of udenafil in Turkish men with erectile dysfunction of psychogenic and organic aetiology: a randomized, double-blind, placebo-controlled study.

Udenafil is a potent phosphodiesterase type-5 inhibitor (PDE5) previously shown in studies conducted in populations of Eastern-Asian ethnicity, to significantly improve sexual function, in addition to a favourable safety profile. The purpose of this study was to evaluate the efficacy and safety of udenafil for the treatment of erectile dysfunction (ED), for the first time in a non-Eastern-Asian population. In this multicentre, randomized, double-blind, parallel, placebo-controlled study conducted in five centres in Turkey, 118 eligible subjects were randomized to receive udenafil 100 mg taken as on-demand or matching placebo for an 8-week treatment period. The primary efficacy variable was the change from baseline of the International Index of Erectile Function Questionnaire-Erectile Function Domain (IIEF-EFD) score, secondary efficacy variables were changes from baseline in IIEF Questionnaire Domains' 2-5 scores (Intercourse Satisfaction, Orgasmic Function, Sexual Desire, Overall Sexual Satisfaction) and IIEF Questionnaire Grand Total score, changes from baseline in penetration success rates (SEP2) and intercourse completion rates (SEP3) and evaluation of responses to the global assessment question (GAQ). Patients treated with udenafil demonstrated significantly higher increase in the IIEF-EFD scores compared with placebo-treated subjects [4.0 (95% CI: 1.3-6.6; p = 0.003)]. Similarly, greater improvements were observed in the scores for SEP2 [0.65 (95% CI: 0.02-1.3, p = 0.043)], SEP3 [0.9 (95% CI: 0.3-1.5, p = 0.003)] and two other IIEF Questionnaire Domains (Domain 4: Sexual Desire, Domain 5: Overall Sexual Satisfaction). The proportion of positive responses to the GAQ was greater in the udenafil compared to the placebo group (72.2% vs. 49.1%, p = 0.014). The most frequent treatment-emergent adverse events were headache, flushing and rhinorrhea, all of mild or moderate severity. This is the first study to demonstrate in a non-Eastern-Asian population that udenafil 100 mg taken as on-demand can effectively improve erectile function and is well tolerated.

Robotic-assisted laparoscopic nephroureterectomy and bladder cuff excision.

BACKGROUND AND OBJECTIVES: Our aim was to show that bladder cuff excision and distal ureterectomy can be safely performed by using the LigaSure device during robotic-assisted laparoscopic nephroureterectomy. METHODS: A 60-year-old man presented with gross hematuria. He was diagnosed with upper urinary tract transitional cell carcinoma (TCC) on the left side and was scheduled for robot-assisted laparoscopic surgery. Without changing the patient's position, sealing with the LigaSure atlas for bladder cuff excision and distal ureterectomy was performed. RESULTS: The operating time was 140 minutes from the initial incision to skin closure of all incisions. The estimated blood loss during the surgery was 120 mL. There were no intraoperative or postoperative complications. The Foley drain was removed on day 3 after normal cystographic findings, and the patient was discharged from the hospital on the fourth postoperative day. CONCLUSION: Robot-assisted nephroureterectomy with distal ureterectomy in the same position using a LigaSure device is a safe alternative for upper tract transitional cell carcinoma.

The actual incidence of papaverine-induced priapism in patients with erectile dysfunction following penile colour Doppler ultrasonography.

Penile color Doppler sonography is a valuable method for evaluating erectile dysfunction. However, there are some concerns about the safety of this method due to the intracorporeal pharmacological injection, which may cause priapism as a complication, resulting in penile fibrosis. To evaluate the actual incidence of papaverine-induced priapism in patients with erectile dysfunction (ED) who underwent penile colour Doppler sonography and to determine the safety of this diagnostic tool, a retrospective study was conducted using the database of our institution. A total of 672 men with ED underwent penile color Doppler ultrasonography with the intracorporeal injection of 60 mg papaverine hydrochloride. The patient characteristics of priapism cases were retrospectively evaluated. Priapism in 18 of the 672 patients (2.68%) was successfully treated with blood aspiration, irrigation and injection of an alpha-agonist medication, when needed. Patients with priapism were younger compared with those without priapism; mean age 45 +/- 12.51 (20-68) versus 50.93 +/- 12.04 (17-78) (P < 0.001). Penile Doppler ultrasound is a safe procedure in evaluating erectile dysfunction. The incidence of priapism, which is the most important complication of this procedure, is low and can be managed successfully with conservative approaches.

Penile blood cyclic guanosin monophosphate level is associated with penile Doppler ultrasound findings.

The aim of this study was to look into a molecule in penile blood sample that shows correlation with the tumescence grade and/or penile Doppler ultrasound findings. Patients admitted to urology outpatient clinic with the complaint of erectile dysfunction between November 2006 and April 2007 were evaluated. Patients with the history of phosphodiesterase inhibitor usage or genital trauma, genital abnormalities, Peyronie's disease, endocrinopathies, cardiovascular diseases and major psychiatric or neurological disorders were excluded. Those patients were later evaluated with a penile Doppler ultrasound, 10-20 min after intracavernosal injection of 60 mg of papaverine hydrochloride. Tumescence grade, peak-systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI) were recorded. Blood samples were drawn from penis and the levels of calcium, myeloperoxidase, malondialdehyde, nitrite, nitrate, vasoactive intestinal peptide and cyclic guanosin monophosphate (cGMP) and the activity of superoxide dismutase were measured. A total of 46 patients with erectile dysfunction were included. The median age of the patients was 49.3+/-10.2 (range 24-67). We could not find any significant correlation between penile Doppler ultrasound parameters and any of penile blood measurements except cGMP that demonstrated a significant negative correlation with PSV (rho=-0.533, P=0.001) and RI (rho=-0.468, P=0.005). However, a positive correlation between cGMP and EDV was detected (rho=0.322, P=0.059). Mean cGMP levels were 3.347+/-0.694 pmol ml(-1) (2.295-4.685), 3.193+/-0.669 pmol ml(-1) (2.165-4.094) and 2.742+/-0.690 pmol ml(-1) (1.290-4.011) in grades 2, 3 and 4 tumescence groups, respectively, and the difference among mean cGMP levels of these groups were statistically significant (P=0.027). As a conclusion, penile blood cGMP level showed a significant negative correlation with mean PSV, RI values and tumescence grade, whereas there was a positive but insignificant correlation between cGMP and mean EDV value.

Turkish validation of the premature ejaculation diagnostic tool and its association with intravaginal ejaculatory latency time.

There are uncertain issues on the diagnostic methods of premature ejaculation (PE). The premature ejaculation diagnostic tool (PEDT) was developed to systematically apply the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria in diagnosing PE and the aim of this study is to carry out the Turkish validation of the PEDT and to evaluate its association with intravaginal ejaculatory latency time (IELT). A total of 94 patients with a self-reported complaint of PE and 88 men without PE were enrolled into the study and requested to complete the nine-item PEDT, which was translated into Turkish. The patients were also requested to measure IELT. All participants were requested to come for a second visit to assess the PEDT's retest reliability; data from 78 men in the PE group and 69 men in the control group were collected. The IELT data of 35 patients were also recorded. The mean age of the PE group and the control group were 39.4+/-9.7 (24-65) and 30.1+/-5.7 (20-56), respectively, (P=0.068). Among the patients in the PE group, 24 (68.5%) reported life-long PE, whereas 11 (31.5%) reported acquired PE. The geometric mean IELT of the PE group was 59.7+/-46.2 (6.5-197.7) s. The number of men reporting IELTs of <1, 1-<2 and >2 min were 20 (57.1%), 11 (31.5) and 4 (11.4%), respectively. The factor analysis assessment showed that the five-item combination (questions 1, 2, 3, 4 and 8) explained 74.4% of the variance, there were no other combinations that explained the variance more effectively. Cronbach's alpha score of five-item combination was calculated as 0.77, showing adequate internal consistency. The overall Cronbach's alpha score did not increase if any item combination was deleted. The test-retest correlation coefficients of each item were higher than 0.80 and the correlation coefficient of the total score was 0.90. The PEDT and IELT showed an adequate correlation (rho=0.44). As a conclusion, the validated five-item Turkish version of PEDT is a reliable questionnaire to screen PE among Turkish patients. Its significant association with IELT supports the fact that PEDT may be of benefit for the diagnosis of PE and measuring the response to treatment. In addition, PEDT seems to be more applicable than measuring IELT in our population, for the assessment of PE.

Auditory event-related potentials in patients with premature ejaculation.

OBJECTIVES: To investigate in a descriptive manner the P300 component of the event-related potential (ERP), which is related to aspects of cognitive processing, in patients with premature ejaculation (PE) to determine whether there is a cognitive alteration in this condition. Recent studies with short latency evoked potentials such as cortical somatosensory evoked potentials have indicated that afferent sensory inputs from the genital area to the nervous system are increased in PE. However, the cortical neural process of ejaculation has remained poorly understood. METHODS: We performed ERPs in 20 patients with PE and in 20 age-matched healthy subjects. ERPs were evoked by an auditory oddball paradigm consisting of 150 tone bursts (80% 1 kHz; 20% 2 kHz). The latencies of the N200 and the P300 waves and the amplitude of the P300 wave were measured. RESULTS: The mean latencies of the N200 and P300 waves were significantly longer in the patients with PE than in the controls (P <0.04 and <0.03, respectively). No significant difference was found in the P300 amplitude between the controls and patients (P >0.05). CONCLUSIONS: These data indicate that the greater cortical representation of sensory stimuli from the genital areas that has been shown with somatosensory evoked potential studies might be related to a cognitive/neurobehavioral dysfunction. The dysfunction involves an increased time to evaluate and categorize the stimuli in the central nervous system, with no change in the quality of cognition and neural disinhibition by the prefrontal cortex to early sensory processing in subcortical or primary cortical regions, which are cognitive neural processes underlying ERP generation.

Evrim Bougie: a new instrument in the management of urethral strictures.

BACKGROUND: In this study a new instrument and technique is described for the endoscopic treatment of complete posterior urethral strictures, which may result in serious complications and sometimes require troublesome treatments. METHODS: Three patients with complete posterior urethral obstruction were treated endoscopically with the guidance of a new instrument: Evrim Bougie. Evrim Bougie looks like a Guyon Bougie, has a curved end, which facilitates getting into the bladder through the cystostomy tract and with a built in channel of 1.5 mm in diameter for a sliding needle exiting at its tip. Having confirmed fluoroscopically and endoscopically that the sliding needle had passed across the strictured segment, the strictured segment was incised with internal urethrotomy, distal to the strictured segment, and urethral continuity was accomplished. At the end of the operation a Foley urethral catheter was easily placed into the bladder per urethra. Patients were instructed in self-catheterization after removal of the urethral catheter. All patients achieved normal voiding at postoperative 7th month follow-up evaluation. CONCLUSION: Internal urethrotomy could be performed under the guidance of the sliding needle of Evrim Bougie advanced from above the posterior urethral strictures, which to our knowledge was described for the first time in the English literature. We also believe that there may be other possible indications of Evrim Bougie for different procedures in urethral surgery.

The role of adrenomedullin in varicocele and impotence.

OBJECTIVE: To assess the levels of adrenomedullin (a vasodilatory peptide) in penile blood before and after injection with papaverine in impotent men, and in the internal spermatic vein in infertile patients with varicocele, comparing the results with levels in the brachial vein in the same patients. PATIENTS AND METHODS: Intracavernosal levels of adrenomedullin were determined in 14 impotent men (with no vascular pathology, as assessed by colour Doppler ultrasonography) before and after papaverine-induced penile erection. The effect of needle puncture alone was assessed in eight control patients. The level of adrenomedullin was also measured in the internal spermatic vein and brachial vein in 14 infertile men with varicocele. RESULTS: The mean (SD) intracavernosal adrenomedullin levels in the 14 impotent men were significantly different between the flaccid and papaverine-induced erectile state, at 93.5 (33.0) and 135.8 (34.9) pmol/mL, respectively, (P < 0.05). Needle puncture alone had no effect on adrenomedullin levels. In men with varicocele, the adrenomedullin level of 139.0 (34.3) pmol/mL within the internal spermatic vein was significantly higher than that in the brachial vein, at 103.9 (37.6) pmol/mL (P < 0.05). CONCLUSION: Injection with papaverine increases adrenomedullin release into penile blood; this release may be responsible for the increase in penile blood flow and penile erection. Higher levels of adrenomedullin within the internal spermatic vein of patients with varicocele may result from the retrograde flow of venous blood from the left adrenal gland and kidney. Further studies are needed to determine the role of adrenomedullin in male infertility and impotence.

Correlation of non-random chromosomal aberrations in lymphocytes of prostate cancer patients with specific clinical parameters.

The purpose of this research was to correlate non-random chromosomal aberrations in the peripheral blood lymphocytes (PBLs) of prostate cancer patients with specific clinical parameters. Peripheral blood samples were analyzed from 59 informative prostate cancer patients. Non-random chromosomal alterations detected in the PBLs and their correlation with any specific clinical parameters were analyzed statistically. A comparison was made between specific chromosomal abnormalities in the patients having an early (<65 years) or late (> or =65 years) age at disease onset, low-grade (Gleason grade <7) or high-grade (Gleason grade > or =7) tumors, a low (<10 ng/ml) or high (> or =10 ng/ml) prostate-specific antigen (PSA) level, and androgen-sensitive or -insensitive disease. In examining the specific chromosomal breakpoints, the regions 1p13, 2q21, 3p21, 4q13, 5q31, 6p21, 7p15, 7p13, 7q32, 10p11, 10q26, 11p15, 11p11, 14q12, and 16q12 showed breaks in at least four cases. Chromosome 15 (P=0. 045) was significantly altered in patients having a PSA value greater than or equal to 10, while it (P=0.017) and chromosome 19 (P=0.036) were significantly altered in patients having a PSA value greater than or equal to 20. In addition, chromosomes 5 (P=0.032), 8 (P=0.020), 16 (P=0.009), and 20 (P=0.047) were significantly altered in patients having a Gleason grade greater than 7. Also, chromosomes 2 (P=0.020) and 3 (P=0.044) were significantly altered in patients who had early disease onset. Additionally, chromosome 10 (P=0.041) was significantly altered in patients having metastasis, and chromosomes 4 (P=0.006) and 7 (P=0.028) were significantly altered in patients having androgen-insensitive disease. In spite of the small subset of patients, chromosome 8 (p=0.003) was significantly altered in patients having small cell carcinoma of the prostate. From these results we conclude that non-random chromosomal aberrations present in PBLs of prostate cancer patients can be correlated with specific clinical parameters. These correlations can be used to identify a prostate cancer patient's risk response to therapy.

Interleukin 8 expression regulates tumorigenicity and metastases in androgen-independent prostate cancer.

Interleukin 8 (IL-8) is mitogenic and chemotactic for endothelial cells. Within a neoplasm, IL-8 is secreted by inflammatory and neoplastic cells. The highly metastatic PC-3M-LN4 cell line overexpresses IL-8 relative to the poorly metastatic PC-3P cell line. We evaluated whether IL-8 expression by human prostate cancer growing within the prostate of athymic nude mice regulates tumor angiogenesis, growth, and metastasis. PC-3P cells were transfected with the full-length sense IL-8 cDNA, whereas PC-3M-LN4 cells were transfected with the full-sequence antisense IL-8 cDNA. Control cells were transfected with the neomycin resistance gene (Neo). In vitro, sense-transfected PC-3P cells overexpressed IL-8-specific mRNA and protein, which resulted in up-regulation of matrix metalloproteinase 9 (MMP-9) mRNA, and collagenase activity, resulting in increased invasion through Matrigel. After antisense transfection of the PC-3M-LN4 cells, IL-8 and MMP-9 expression, collagenase activity, and invasion were markedly reduced relative to controls. After orthotopic implantation, the sense-transfected PC-3P cells were highly tumorigenic and metastatic, with significantly increased neovascularity and IL-8 expression compared with either PC-3P cells or controls. Antisense transfection significantly reduced the expression of IL-8 and MMP-9 and tumor-induced neovascularity, resulting in inhibition of tumorigenicity and metastasis. These results demonstrate that IL-8 expression regulates angiogenesis in prostate cancer, in part by induction of MMP-9 expression, and subsequently regulates the growth and metastasis of human prostate cancer.