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Objective: Chromosomal changes are an important cause of reproductive disorders. This study investigated the chromosomal changes and prevalence of pathologies in individuals admitted to our Genetic Evaluation Center over a 10-year period due to a reproductive disorder., Materials & Methods: The chromosomal findings of 4345 individuals with reproductive disorders who applied to our Genetic Evaluation Center at Akdeniz University in Antalya, Turkey between 2011 and 2021 were retrospectively evaluated., Results: In this study, an abnormal karyotype was found in a total of 138 individuals (87 males and 51 females). Although the incidence of this abnormal karyotype varied among the diseases in the reproductive disorder subgroups, it was most frequently seen in azoospermia (17.0%). Of the 138 abnormalities, 75 were numerical and 54 were structural. The remaining 9 abnormalities consisted of 6 sex reversals and 3 patients with both numerical and structural anomalies. Additionally, the X chromosome was the chromosome most frequently involved in these abnormalities, being observed in 40.6% of patients., Conclusion: This 10-year, single-center study involved one of the largest case series in the literature to investigate the subtypes of reproductive disorders and their chromosomal relationship. Although the importance of chromosome analysis has been deemphasized, it is still recommended for use by the guidelines and, as the results of this study demonstrate, is still a highly effective method in the investigation of reproductive disorders. Furthermore, chromosome analysis of individuals diagnosed with a reproductive disorder is also very important in the practice of the increasingly utilized preimplantation genetic diagnosis (PGD)., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

To investigate, if advanced glycation end products (AGEs) are involved in erectile dysfunction (ED) and also ALT-711, a cross-link breaker of AGEs, has the therapeutic potential against the development of ED in rats treated with high concentrated AGEs including food. For this purpose, 30 male Harlan Spraque-Dawley rats randomly were divided into three groups; (1) control rats treated with regular diet, (2) rats treated with high-level of AGE specific diet for 6 months, and (3) rats having AGE-diet treated with ALT-711 for the final 3 months of 6 months of AGE-diet period. Erectile response to cavernosal nerve stimulation (CNS), protein expression of neuronal nitric oxide synthase (nNOS) and levels of AGEs, Malondialdehyde (MDA), cyclic guanosine monophosphate (cGMP) were determined in penile tissues. Erectile responses to CNS and penile nNOS and cGMP content were significantly reduced, while AGEs and MDA were elevated in penises of Group-2. Treatment with ALT-711 reversed ED and depletion of both nNOS and cGMP. Additionally, ALT-711 treatment reduced penile tissue AGEs and MDA expression. In present study: rats without any co-morbidity such as diabetes mellitus (DM) and chronic renal failure (CRF) were treated with high-level AGEs containing food. Our results suggest that ALT-711 may be an interesting and promising approach in the treatment of AGEs-related ED., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Erectile dysfunction (ED) is a common condition which reduces quality of life of both patients and their partners, and is a significant health care expense every year. Although phosphodiesterase type-5 inhibitors are the current first-line treatment for men with ED, they are limited by their on-demand dosing, intolerance, and variable efficacy in complex patient populations such as men with multiple medical comorbidities or ED after pelvic surgery. Regenerative medicine has been introduced and investigated in andrology as an encouraging strategy to restore diseased erectile tissue structure and function. Novel regenerative therapies for ED are controversial but are perceived to offer a durable and safe tissue restorative approach to act as a long-term solution to this cumbersome disease process. Here, we review platelet-rich plasma, amniotic fluid membranes, low-intensity extracorporeal shockwave therapy, and stem cell therapy as regenerative strategies to treat ED. Most of these approaches have preclinical and occasionally clinical data to support their ongoing investigation; however, none of these treatments are currently supported for use in ED patients outside of clinical trials., Competing Interests: Conflicts of Interest: The focused issue “Contemporary Issues and Controversies in Men’s Health” was commissioned by the editorial office without any funding or sponsorship. The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

Background: Little is known about sperm health in male patients with familial Mediterranean fever (FMF). In this study, the authors aimed to search the frequency of sperm abnormalities of adolescent boys with FMF and also to investigate whether disease activity or colchicine treatment have negative effects on sperm parameters., Method: The male adolescents older than 14 years with a diagnosis of FMF were investigated retrospectively. Tel Hashomer and pediatric FMF clinical criteria were used for diagnosis of FMF. Patients who had semen analysis were included in the study., Result: Mean age at the diagnosis was 11.13 ± 3.82 years, and mean age at the study was 14.50 ± 0.70 years. The mean sperm concentration was found as 66.26 ± 41.02 million/ml (N > 15 million/ml), the mean total sperm count 113.42 ± 132.39 million (N > 39 million), and the mean sperm motility 51.78 ± 23.70% (N > 40%). Only 8 of 19 (42.1%) patients had normal sperm parameters. Sperm concentration was reduced in two cases, total sperm count was reduced in four patients, and motility was reduced in nine cases. The presence of FMF attacks under treatment was found to be a risk factor for decreased motility in the study group by multivariate regression analysis (odds ratio 0.076, [95% confidence interval 0.005-0.648], P = 0.031). Erythrocyte sedimentation rate at the time of diagnosis was high in patients with low sperm counts compared with those with normal sperm counts (56.00 ± 8.51 vs 24.35 ± 6.32, P: 0.03). Mean colchicine dose at the time of sperm analysis was higher in patients with low sperm motility than that with normal sperm motility (1.72 ± 0.18 vs 1.25 ± 0.08, P: 0.02)., Conclusion: Sperm abnormalities of male patients with FMF is not infrequent, and it is linked to both inflammation due to uncontrolled disease and colchicine therapy., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Low-intensity extracorporeal shockwave therapy (LI-ESWT) to the penis has recently emerged as novel therapeutic option in the treatment of erectile dysfunction (ED). Randomized-controlled studies investigating the effect of this new treatment modality revealed promising results in men with vasculogenic ED. However, the efficacy of LI-ESWT in men who develop ED following radical prostatectomy (RP) remains obscure due to the exclusion of this group in nearly all clinical trials. In this review, the authors synthesize the findings from available preclinical and clinical studies that examine the potential utility of LI-ESWT in men with post-RP ED.

Objective: Previous study conducted by the Turkish Society of Andrology in 1999 reported the prevalence of erectile dysfunction (ED) as 69.2% in men of ≥40 years of age, using a single-item non-validated question. This rate seemed to be higher compared to the studies reported worldwide. So, there was a need to carry out another epidemiological study by using validated questionnaires. Our aim was to investigate ED prevalence, severity, and its correlates in men aged ≥40 years using validated tools., Material and Methods: This cross-sectional, observational, population-based field survey was carried out in randomly selected males of ≥40 years from 19 provinces of Turkey. All participant completed a survey included with socio-demographic and socio-economic characteristics, medical and sexual history, associated physical and medical comorbidities. Erectile function was assessed by the International Index of Erectile Function (IIEF) questionnaire based on a total score of 30. The prevalence of ED, its severity and correlates in men aged ≥40 years were determined for main outcome measures. Data sets were statistically compared and p<0.05 was considered as significant., Results: Median age of 2.760 males was 54.2 years. The median prevalence of ED was calculated as 33% among all males of ≥40 years of age. When subjects were stratified by age; median ED prevalence rates were 17% for 40-49 years, 35.5% for 50-59 years, 68.8% for 60-69 years, and 82.9% for ≥70 years. Among all ED men, 76.9% reported mild, 16.3% moderate, and 5.7% severe ED. At logistic regression analyses; age, diabetes, hypertension, atherosclerosis, dyslipidemia, lower urinary tract symptoms, educational status and monthly income were found to be independent risk factors for having ED., Conclusion: This population-based survey in Turkish men of ≥40 years of age reported the prevalence of ED as 33%. Besides, this study reported age as the main predictor for presence and severity of ED., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Penile traction therapy (PTT) is a new therapeutic option for men with Peyronie's disease (PD). However, it has a long history of use in other fields of medicine including bone, skin, skeletal muscle, and Dupuytren's. Mechanotransduction, or gradual expansion of tissue by traction, leads to the formation of new collagen tissue by cellular proliferation. As a molecular result, continuous extension of the fibrous plaque causes significant increases in collagenase and metalloproteinases, and, ultimately, to fibrous plaque softening and extension. This hypothetical knowledge has been supported by recent well designed experimental studies. Furthermore, several clinical papers have provided promising results on the use of PTT in PD patients. It has been shown in some series that the use of PTT significantly increases flaccid and stretched penile lengths and results in significant penile curvature improvement when compared to baseline. Furthermore, the use of PTT concomitantly with either verapamil or interferon α-2b has also been shown to be an effective therapy. Additionally, the beneficial effect of PTT on penile length before or after penile surgery in men with corporal fibrosis has been described. Finally, as a minimally invasive alternative treatment option to penile augmentation surgery in men with dysmorphophobia, PTT use has shown promising results by several experts. Studies have shown that PTT provides an acceptable, minimally invasive method that can produce effective and durable lengthening of the penis in men complaining of a small/short penis. There are, however, several criticisms related to the designs of the reported studies, such as small sample size and selection bias. Well-designed studies with larger numbers of patients and longer follow-up periods are, however, needed to establish the true benefits of PTT.

Purpose: Azoospermia is one of the major causes of male infertility and is basically classified into obstructive (OA) and non-obstructive azoospermia (NOA). The molecular background of NOA still largely remains elusive. It has been shown that the poly(A)-binding proteins (PABPs) essentially play critical roles in stabilization and translational control of the mRNAs during spermatogenesis., Methods: In the present study, we aim to evaluate expression levels of the PABP genes, EPAB, PABPC1, and PABPC3, in the testicular biopsy samples and in the isolated spermatocyte (SC) and round spermatid (RS) fractions obtained from men with various types of NOA including hypospermatogenesis (hyposperm), RS arrest, SC arrest, and Sertoli cell-only syndrome (SCO)., Results: In the testicular biopsy samples, both PABPC1 and PABPC3 mRNA expressions were gradually decreased from hyposperm to SCO groups (P < 0.05), whereas there was no remarkable difference for the EPAB expression among groups. The expression levels of cytoplasmically localized PABPC1 and PABPC3 proteins dramatically reduced from hyposperm to SCO groups (P < 0.05). In the isolated SC and RS fractions, the EPAB, PABPC1, and PABPC3 mRNA expressions were gradually decreased from hyposperm to SC arrest groups (P < 0.05). Similarly, both PABPC1 and PABPC3 proteins were expressed at higher levels in the SC and RS fractions from hyposperm group when compared to the SC and RS fractions from either RS arrest or SC arrest group (P < 0.05)., Conclusion: Our findings suggest that observed significant alterations in the PABPs expression may have an implication for development of different NOA forms.

The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg-1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P < 0.05). The increase in both intracavernosal pressure (ICP) and area under the curve of CRF-induced rats treated with sildenafil (Group 3) was greater than CRF-induced rats (Group 2). Additionally, sildenafil treatment decreased AGE, MDA and iNOS levels, while it preserved nNOS and cGMP contents in CRF-induced penile tissue. Decreased AGE, MDA, iNOS and increased nNOS, cGMP levels at the sildenafil-treated group increased both ICP and Total ICP to CNS, which led to improve erectile function in CRF-induced rats. The results of the present study revealed the therapeutic effect of chronic sildenafil administration on erectile function in CRF-induced rats.

The objective of this study was to determine the prevalence of male pelvic dysfunction (MPD) and its correlation in men ≥40 years of age in a population-based study. This study was designed as a non-interventional, observational, cross-sectional field survey. Participating males of ≥40 years were randomly selected from 19 provinces of Turkey. All participants were asked to complete a survey including data regarding demographics, socio-economic status, socio-cultural factors, medical and sexual history, current medications, comorbidities and three validated questionnaires assessing lower urinary tract symptoms (International Prostate Symptom Score), erectile dysfunction (International Index of Erectile Function) and ejaculatory behaviour (Male Sexual Health Questionnaire-4). MPD was defined by combining abnormal scores calculated from all three questionnaires. All data were analysed statistically and p < 0.05 was accepted as significant. A total of 2730 males of ≥40 years (mean, 54.2 ± 10.6 years) were enrolled in this study. The prevalence of MPD was calculated as 24.4% among all participants. The prevalence of MPD was lowest at age between 40 and 49 years (9.1%) and highest at ≥70 years (76.6%), exhibiting correlation with age. Each decade of increase in age was associated with a 3.4-fold increase in presence of MPD. At logistic regression analyses; age, diabetes, hypertension, dyslipidemia, cardiovascular disease, obesity and lower income were found to be independent predictors for increased prevalence of MPD. This study reports prevalence of MPD as 24.4% in males of ≥40 years. Furthermore, age was found to be the main independent predictor of having MPD., (© 2013 American Society of Andrology and European Academy of Andrology.)

Erectile dysfunction (ED) is the most common male sexual problem worldwide. The association between ED and components of metabolic syndrome (MtS) is well established. This study examined neck circumference (NC) as a possible indicator of MtS and also of ED. Ninety-two patients were included and divided into two groups. Group 1 consisted of 47 patients with ED and Group 2 consisted of 45 healthy volunteers. Questionnaires, differences in anthropometric and laboratory measurements between patients with ED and the control group, and a cut-off value for NC were investigated. The mean NC in ED patients was higher in Group 1 than in Group 2 (P = 0.001), and Group 1 also demonstrated more MtS criteria than Group 2 (P < 0.001). The cut-off point of NC was defined as 34.75 cm for ED and MtS. The cut-off values of waist circumference for ED and MtS were 105.5 and 102.5 cm respectively. In the light of these findings, NC may be a new component of MtS in ED patients. Additionally, NC may be a novel indicator of central obesity and ED. We suggest that NC values of 35 cm and over may predict ED in patients with MtS., (© 2013 Blackwell Verlag GmbH.)

Objective: To evaluate the changing cavernosal length of patients with diabetes mellitus (DM) and organic erectile dysfunction (ED) who were treated with inflatable, three-piece penile prostheses, a current surgical treatment option in our clinic, over the course of 12 years., Materials and Methods: Between April 2000 and December 2012, we retrospectively investigated data from patients who were diagnosed with organic ED and undergone penile prosthesis implantation (PPI). Of the 239 patients, 235 of them were included in the study. Four patients who were operated on for trans-sexuality were excluded from the study. All patients were divided into two groups as those with (Group 1) or without DM (Group 2). Data, including age, body mass index (BMI) in kg/m(2), surgical history, comorbidities, International Index of Erectile Function (IIEF) questionnaire scores, combined intracavernous injection and stimulation (CIS) test results, length of corpus cavernosum while implanting the penile prosthesis, complications, operative times, mean hospital stay, and satisfaction of the patient and partner, were recorded. Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis. A p-value of <0.05 was considered to be statistically signifcant., Results: The mean age was 57.9±10.5 years. Study population consisted of patients with DM (n=65), hypertension (n=21), DM, and hypertension (n=28), hyperlipidemia (n=5), a history of previous radical pelvic surgery with (n=4) or without DM (n=51) or cases without any comorbidity (n=62). Mean length of the corpus cavernosum was 17.277±0.1509 cm in Group 1 and 17289±0.1598 cm in Group 2 (p<0.05). Additionally, the other parameters, including age, operative time, and the satisfaction of the patient and partner, were not different between these groups (p>0.05)., Conclusion: The length of the corpus cavernosum and the destruction of cavernosal tissues do not depend only on DM. We conclude that these features may have multifactorial causes.

In this report we describe the first patient ever found to have azoospermia in association with both exceptional complex chromosomal rearrangements and microdeletions at two translocation breakpoints. A 36-year-old male who had been suffering from male factor infertility was admitted to our clinic. The patient also displayed mild dysmorphia. An analysis of the patient's semen revealed azoospermia. GTG banding revealed the presence of an exceptional complex chromosomal rearrangement involving chromosomes 1, 4, 10 and 14. Using subtelomeric FISH analysis, the patient's karyotype was designated as 46,XY,t(1;10)(q43q44;q21q26.1)(CEB108/T7+,D1S3738-;10PTEL006+,D10S2290+, D1S3738+), ins(14;4) (q31.3;q23q33)(D14S1420+; D4S3359+, D4S2930+). Array-CGH analysis revealed two microdeletions at the 4q22.3q23 and 14q31.1q31.3 chromosomal regions. We suggest that microdeletions at the 4q22.3q23 and 14q31.1q31.3 chromosomal regions associated with both an exceptional complex chromosomal rearrangement and the Homo sapiens chromosome 4 open reading frame 37 (C4orf37) gene located at the 4q22.3q23 region might be associated with male factor infertility., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Environmental exposure to pesticides may cause serious health risks including fertility and reproductive function. The aim of this study was to highlight whether there is a relationship between exposure to abamectin and male fertility parameters of farmworkers. Twenty male farmworkers who were using abamectin and 20 men not exposed to pesticides were recruited as experimental and control groups, respectively. Semen analysis, molecular markers of sperm maturity and serum reproductive hormone levels were evaluated. In experimental group, high plasma abamectin levels were detected. These men have decreased sperm motility. Moreover, diminished molecular markers of sperm maturity, such as decreased hyaluronic acid (HA) binding of sperm, increased numbers of aniline blue positive sperm and increased percentage of creatine kinase (CK) positive sperm, were observed in abamectin-exposed men. Their serum testosterone, LH and FSH levels did not change significantly. We conclude that exposure to abamectin may impair male fertility by effecting semen quality., (© 2012 Blackwell Verlag GmbH.)

Recently, the relationship between advanced glycation end products (AGEs) and erectile dysfunction (ED) has been reported. The present study aimed to investigate whether a combination of an AGE cross-link breaker (alagebrium/ALT-711) and sildenafil could enhance the erectile capacity in streptozotocin (STZ) diabetic rats. Additionally, we assessed the effect of that treatment option on some molecules that have been suggested to have crucial roles in AGE-related ED pathways. Four groups of animals were utilized: (1) age-matched control rats, (2) STZ-induced diabetic rats (40 mg kg(-1) i.p.), (3) STZ rats+sildenafil (5 mg kg(-1) p.o.), (4) STZ rats treated with a combination of sildenafil (5 mg kg(-1) p.o)+alagebrium/ALT-711 (10 mg kg(-1) p.o.) for the final 1 month of the 2 months of diabetes period. At 2 months after i.p. injection of STZ, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue AGEs, MDA (malondialdehyde), cyclic guanosine monophosphate (cGMP) (ELISA), endothelial nitric oxide (NO) synthase (eNOS), inducible NO synthase (iNOS) (western blot), nuclear factor (NF)-κB, mitogen-activated protein (MAP) kinase (immunohistochemistry) and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) analyses were performed in all groups of rats. STZ diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve) after CNS when compared with control rats (P<0.05). The increase in both ICP and area under the erectile curve of STZ diabetic rats treated with a combination of sildenafil+alagebrium/ALT-711 as well as in STZ diabetic rats treated with sildenafil alone was significantly greater than STZ diabetic rats. Additionally, combination treatment decreased AGE, MDA, iNOS, NF-κB, MAP kinase and apoptosis levels, whereas it preserved cGMP contents in diabetic penile tissue. Decreased AGE, MDA, iNOS, NF-κB, MAP kinase and increased cGMP levels at the combination (sildenafil+alagebrium/ALT-711) therapy group increased both the peak ICP and total ICP to CNS in the STZ diabetic rats, which was similar to the response observed in control rats. These results may explain the role of AGEs in diabetes-related ED and the effect of an AGE cross-link breaker alagebrium/ALT-711+sildenafil therapy on some critical molecules related to AGE-related ED pathways.

Introduction: In addition to the previously defined "lifelong" and "acquired" premature ejaculation (PE), the existence of two more subtypes of PE, namely "natural variable PE" and "premature-like ejaculatory dysfunction," has been proposed., Aims: To evaluate the diagnostic value of the Premature Ejaculation Diagnostic Tool (PEDT) and Arabic Index of Premature Ejaculation (AIPE) in a population-based study, in relation to their sensitivity across these four different PE syndromes and to assess the Premature Ejaculation Profile (PEP) scores of patients with lifelong, acquired, natural variable PE and premature-like ejaculatory dysfunction., Methods: Between June 2009 and December 2009, couples were randomly selected from 17 provinces of Turkey. Subjects with the complaint of ejaculating prematurely were classified as lifelong, acquired, natural variable PE, and premature-like ejaculatory dysfunction according to the medical and sexual history they described. PE status was also assessed with PEDT, AIPE and PEP. The sensitivity, specificity, positive predictive value and negative predictive value were calculated for PEDT and AIPE in the study population whereas detection rates of these two questionnaires were also compared among the four PE syndromes. Moreover, PEP scores of patients with lifelong, acquired, natural variable PE and premature-like ejaculatory dysfunction were compared. Significance level was considered as P < 0.05., Main Outcome Measures: Scores obtained from PEDT, AIPE, and PEP questionnaires., Results: A total of 2,593 couples were enrolled where 512 (20.0%) male subjects reported PE. PEDT, AIPE, and PEP measures of the PE patients indicated worse sexual function (P < 0.001 each). Mean scores obtained from questionnaires were significantly better in patients with premature-like ejaculatory dysfunction and they were the worst in patients with acquired PE (P < 0.001 each). The sensitivity values of PEDT and AIPE were 89.3 and 89.5, whereas their specificity values were 50.5 and 39.1, respectively. There were statistically significant differences in detection rates of PEDT and AIPE among the four PE syndromes (P = 0.006 and P < 0.001). They were higher in acquired and lifelong PE and lower in premature-like ejaculatory dysfunction., Conclusion: PEDT and AIPE can diagnose PE with high sensitivity, especially in patients with lifelong and acquired PE. The complaint of patients with acquired PE seems to be more severe than those complaining of lifelong, natural variable PE and premature-like ejaculatory dysfunction patients., (© 2011 International Society for Sexual Medicine.)

Introduction: In addition to the previously known lifelong and acquired premature ejaculation (PE) syndromes, the existence of two more PE syndromes has been suggested: natural variable PE and premature-like ejaculatory dysfunction. However, epidemiological studies investigating the prevalence of these four PE syndromes have yet to be conducted., Aim: To determine the prevalence of the complaint of ejaculating prematurely across the four PE syndromes., Methods: This study, conducted between June 2009 and December 2009, was designed as a non-interventional, observational cross-sectional field survey. Participating couples were randomly selected from 17 provinces of Turkey. All participants were asked to complete a questionnaire including data regarding demographics, socioeconomic status, social and cultural factors, medical and sexual history, current medications, and ejaculation time. Subjects with a complaint of ejaculating prematurely were classified as lifelong, acquired, and natural variable PE, or premature-like ejaculatory dysfunction., Main Outcome Measures: The main outcome measures were prevalence of complaint of ejaculating prematurely in the general population and across the four PE syndromes., Results: A total of 2,593 couples (mean age, 41.9±12.7 years for males and 38.2±12.1 years for females) were enrolled. Five-hundred twelve subjects (20.0%) complained of ejaculating prematurely. Fifty-eight (2.3%), 100 (3.9%), 215 (8.5%), and 131 (5.1%) subjects were classified as lifelong, acquired, and natural variable PE, and premature-like ejaculatory dysfunction, respectively., Conclusions: The prevalence of the complaint of ejaculating prematurely among Turkish men was 20.0%, with the highest PE syndrome being natural variable PE (8.5%) and premature-like ejaculatory dysfunction (5.1%)., (© 2010 International Society for Sexual Medicine.)

The aim of this study was to analyze the semen variables and hormone profiles in kidney transplanted male adolescents. Eight post-pubertal male patients who underwent successful renal tx during the peripubertal period and who had ESRD during childhood were enrolled in the study. Patients who underwent tx before 14 yr old (group I) and patients who underwent tx after 14 yr old (group II) were evaluated separately. Semen was collected and analyzed. Serum levels of LH, FSH, and testosterone were measured and found to be normal in all patients except one. The mean age at the diagnosis of CKD was six yr and 13 yr in groups I and II, respectively. The mean age at the time of tx was 12 yr in the first and 17.8 yr in the second group. The patients in group I had received prednisone, cyclosporine A and azathioprine with a longer duration of time compared with patients in group II. Sperm counts (15.5 +/- 15.7 vs. 82.3 +/- 64.2 millions/mL) and sperm motilities (37.8 +/- 30.9 vs. 57.8 +/- 22.1%) were lower in group I than group II. Only one patient in group II had normal sperm parameters and azospermia was observed in one patient from group I. We conclude that the earlier onset and the longer duration of uremia, the more impairment of reproductive function. Also, it seems that duration of exposure to corticosteroids or cyclosporine combined with azathioprine contribute to sperm dysfunction in peripubertal transplanted boys.

In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capacity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency. The critical role of androgens on the development, growth, and maintenance of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function. Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. Furthermore, androgen deprivation caused to accumulation of fat containing cells and decreased protein expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS), and phosphodiesterase type-5 (PDE-5), which play crucial role in normal erectile physiology. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintenance of penile tissue and erectile physiology as well. Furthermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalence, diagnosis and treatment options of hypogonadism in aging men.

Mesenchymal stem cells (MSCs) can be used in adult stem cell-based gene therapy for vascular diseases. To test the hypothesis that MSCs alone or endothelial nitric oxide synthase (eNOS)-modified MSCs can be used for treatment of erectile dysfunction (ED), syngeneic rat MSCs (rMSCs) were isolated, ex vivo expanded, transduced with adenovirus containing eNOS, and injected into the penis of aged rats. Histological analysis demonstrated that rMSCs survived for at least 21 days in corporal tissue after intracavernous injection, and an inflammatory response was not induced. Intracavernous administration of eNOS-modified rMSCs improved the erectile response in aged rats at 7 and 21 days after injection. The increase in erectile function was associated with increased eNOS protein, NOS activity, and cGMP levels. rMSCs alone increased erectile function of aged rats at day 21, but not at day 7, with the transplanted cells exhibiting positive immunostaining for several endothelial and smooth muscle cell markers. This change in rMSC phenotype was accompanied by upregulation of penile eNOS protein expression/activity and elevated cGMP levels. These findings demonstrate that an adenovirus can be used to transduce ex vivo expanded rMSCs to express eNOS and that eNOS-modified rMSCs improve erectile function in the aged rat. Intracavernous injection of unmodified wildtype rMSCs improved erectile function 21 days after injection through mechanisms involving improved endothelium-derived NO/cGMP signaling and rMSC differentiation into penile cells expressing endothelial and smooth muscle markers. These data highlight the potential clinical use of adult stem cell-based therapy for the treatment of ED.

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.

Objectives: Accumulation of advanced glycation end products (AGEs) has been linked to many of the complications of diabetes mellitus, including erectile dysfunction (ED). Furthermore, it has been demonstrated that inhibitors of AGE formation, such as aminoguanidine, can prevent ED in diabetic animals. However, it is unknown whether late administration of a putative cross-link breaker, ALT-711, can reverse diabetic ED. We therefore compared ALT-711 and aminoguanidine in their ability to reverse ED in diabetic rats., Materials and Methods: Male Sprague-Dawley rats were randomly divided into four groups: (i) age-matched controls; (ii) streptozotocin (STZ)-induced diabetic rats (60 mg/kg; intraperitoneal injection); (iii) STZ diabetic rats treated with ALT-711 (3 mg/kg/day, intraperitoneal injection); and (iv) STZ diabetic rats treated with aminoguanidine (1 gm/L in drinking water) during the final 6 weeks of 12 weeks of induced diabetes. At the end of 12 weeks, erectile response to cavernous nerve stimulation (CNS) was determined. Neuronal nitric oxide synthase (nNOS) contents were measured in all penises, and AGE levels were determined both in penile tissues and in serum samples., Results: Erectile responses to CNS and penile nNOS protein content were significantly reduced, while AGE levels were elevated in the penises and serum of untreated diabetic animals. Treatment with ALT-711, but not with aminoguanidine, reversed ED and nNOS depletion and reduced serum and penile tissue AGE levels., Conclusions: These results suggest that cross-link breakers, such as ALT-711, are the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in the reversal of diabetes-related ED.

Purpose: We investigated the involvement of poly(adenosine diphosphate-ribose) (PAR) polymerase (PARP) activation in the development of erectile dysfunction and the therapeutic benefit of the potent PARP inhibitor INO-1001 (Inotek Pharmaceuticals Corp., Beverly, Massachusetts) in a bilateral cavernous nerve crush injury (BCNCI) model in rats., Materials and Methods: Sprague-Dawley rats were divided into 3 groups, namely sham treated, BCNCI plus vehicle and BCNCI plus the PARP inhibitor INO-1001. One week after surgical intervention all groups underwent in vivo cavernous nerve stimulation. PAR activation, nitrotyrosine and inducible nitric oxide synthase were evaluated by immunohistochemistry and serum levels of INO-1001 were measured by high performance liquid chromatography. Penile tissues were analyzed for levels of malondialdehyde and myeloperoxidase. Data sets were statistically compared in all groups., Results: Neurogenic mediated erectile responses were evaluated. Mean intracavernous pressure (ICP), the ICP-to-blood-pressure ratio and total ICP were significantly decreased in BCNCI plus vehicle rats. These values were not statistically different between the sham and PARP inhibitor treated groups. There was a marked decrease in PAR staining in the treatment group. There was a substantial increase in malondialdehyde tissue levels but not myeloperoxidase in response to BCNCI, which was unchanged with PARP inhibitor treatment. There was a marked increase in tyrosine nitration in the treatment group. Up-regulation of nitric oxide synthase and increased tyrosine nitration were not observed in the penile tissues of the treatment group., Conclusions: These data demonstrate that BCNCI in a rat model causes increased PARP activation, resulting in severe erectile dysfunction. Treatment with the PARP inhibitor INO-1001 decreases the degree of nitrosative stress, prevents PARP activation and provides significant cavernous neuroprotection, which in turn preserves erectile function.

Introduction: Penile duplex Doppler ultrasound (PDDU) is currently the preferred method for the functional evaluation of penile hemodynamics. PDDU may be used to monitor objectively changes in penile vascular parameters in men who undergo treatment for Peyronie's disease (PD), including intralesional interferon alpha-2b (IFN alpha-2b)., Aim: To investigate the impact of intralesional IFN alpha-2b therapy for PD on penile hemodynamics by using PDDU and to assess the objective role of PDDU in monitoring treatment outcomes., Materials and Methods: Thirty-nine patients (20 in the placebo and 19 in the IFN alpha-2b treatment arm) were enrolled in this prospective, placebo-controlled, parallel study. Patients received either 10 mL saline or 5 x 10(6) units of IFN alpha-2b intralesional injections every other week for a total of six injections. Patients in each group were evaluated at baseline and after completion of treatment regarding changes in penile hemodynamic parameters, penile curvature, plaque size and density, pain on erection, and erectile function. Specific published criteria were used for PDDU measurements. Outcomes were statistically compared between each group by using Mann-Whitney U and chi-square tests., Results: The mean age of the patients and the duration of PD were similar in both groups. The improvement in penile blood flow was significantly greater in IFN alpha-2b-treated patients than those in the placebo group. The number with the nonvascular classification increased significantly in the IFN alpha-2b arm from 31.5% to 57.8%. Additionally, improvements in penile curvature, plaque size and density, and pain on erection were better in the IFN alpha-2b group compared with the control. No significant improvement was observed in the erectile function domain in either group., Conclusion: This study reveals that intralesional IFN alpha-2b injections have a significant benefit on penile hemodynamic parameters. Moreover, intralesional IFN alpha-2b is an effective, minimally invasive treatment for PD, and PDDU is a useful adjunct to monitor objectively changes in penile vascular parameters. interferon alpha-2b injection therapy on penile hemodynamics in men with Peyronie's disease.

Introduction: Superoxide anion may contribute to erectile dysfunction (ED) in diabetes mellitus by reducing cavernosal nitric oxide (NO) bioavailability. The purpose of this study was to determine if gene transfer of extracellular superoxide dismutase (EC-SOD) can reduce superoxide anion formation and determine if this reactive oxygen species may contribute to diabetes-related ED in an experimental model of diabetes., Methods: Three groups of animals were utilized: (1) control; (2) streptozotocin (STZ)-diabetic rats [60 mg/kg intraperitoneally (ip)] intracavernosally injected with AdCMVbetagal (negative control); and (3) STZ-rats intracavernosally injected with AdCMVEC-SOD. Two months after ip injection of STZ, groups 2 and 3 were transfected with the adenoviruses and 2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Confocal microscopy for superoxide anion and von Willebrand Factor (vWF) was performed in the STZ-diabetic rat. Superoxide anion production, total SOD activity, and cyclic guanosine monophosphate (cGMP) levels were measured in each experimental group of rats., Results: Confocal microscopy demonstrated superoxide in smooth muscle and endothelial cells of the STZ-rat cavernosum and colocalized with vWF in the endothelium. Higher superoxide anion levels and decreased cGMP levels were found in the penis of STZ-rats at a time when erectile function was reduced. Two days after administration of AdCMVEC-SOD, superoxide anion levels were significantly lower in the penis of STZ-rats. Total SOD activity and cavernosal cGMP was increased in the penis of EC-SOD-transfected rats. STZ-rats transfected with AdCMVEC-SOD had a peak intracavernosal pressure (ICP) and total ICP to CNS that was similar to control rats., Conclusions: These data demonstrate that in vivo adenoviral gene transfer of EC-SOD can reduce corporal superoxide anion levels and raise cavernosal cGMP levels by increasing NO bioavailability thus restoring erectile function in the STZ-diabetic rat.

The objective of this study was to investigate mast cells and iNOS expression in testis tissue, and to correlate these results with spermatogenic disorders. A total of 136 testicular biopsies were obtained from the testes of 80 patients with infertility. Their age ranged from 21 to 45 years. The biopsy specimens were immunohistochemically stained with antihuman tryptase for mast cells. In each section, all interstitial fields were evaluated for the total number of mast cells as well as the total number of Leydig cells. The number of mast cells per Leydig cell was calculated and recorded as mast cell index. Immunohistochemical iNOS staining was evaluated semiquantitatively according to intensity and the proportion of the stained cells. There was a significant increase of the mast cell index in all groups with testicular disorder compared with normal spermatogenesis group (p < 0.05). Increase of the index was in the order of hypospermatogenesis, maturation arrest and SCO, and index of SCO group was especially higher, i.e, more than twice than other groups. iNOS score was significantly higher in the SCO group than in the men with normal spermatogenesis, hypospermatogenesis, and maturation arrest (p < 0.05). Finally, a significantly statistical correlation was found between the iNOS score and mast cells index (r = 0.758, p = 0.001). Increase of mast cell index was observed in the groups of infertile testis, and high expression of iNOS in Leydig cells was associated with the highest mast cell index in SCO, the lesion with the most severe damage of the germ cell.

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.

We report a case of 41-year-old man with idiopathic prostatic giant calculi presenting with voiding difficulty. To our knowledge this is the youngest case with idiopathic prostatic giant calculi reported in the literature. The etiopathogenesis of prostatic calculi are also discussed.

Introduction: The prognostic significance of PTEN protein loss in bladder cancer is not well established. The objective of this study was to investigate the PTEN expression profile in superficial noninvasive papillary transitional cell carcinoma (TCC) versus invasive TCC and compared the results with pathological and clinical parameters., Materials and Methods: Bladder tumor samples were obtained from 29 patients who underwent surgery for superficial (n=11) and invasive (n=18) bladder cancers at the Akdeniz University Hospital. The patient profile including sex, age, histological grade and the stage, presence of carcinoma in situ, cystoscopy findings (tumor size, location, multiplicity) were obtained by examining the patients' medical records. No patient received anticancer agents prior to the operation. Western blotting was performed using bladder carcinoma samples in order to determine the level of PTEN protein expression for each patient., Results: Only 4 (13.7%) patients with bladder carcinoma manifested a decrease in the level of PTEN expression. Regarding the correlation between tumor stage and the PTEN expression, with the exception of patient 23 all patients who displayed a reduction in PTEN expression had muscle-invasive TCC., Conclusion: Future studies with a clinical follow-up will be needed to determine if those superficial tumors with decreased PTEN expression are going to progress to a later stage. Based on our results PTEN by itself does not seem to be a good candidate as an independent marker to predict the behavior of bladder cancers., (Copyright (c) 2005 S. Karger AG, Basel.)

Basic science research on erectile physiology has been devoted to investigating the pathogenesis of erectile dysfunction (ED) and has led to the conclusion that ED is predominately a disease of vascular origin. It is well recognized that the incidence of ED dramatically increases in men who suffer from diabetes mellitus, hypercholesterolemia, and cardiovascular disease. Endothelial nitric oxide synthase (eNOS) is an important factor in cardiovascular homeostasis, angiogenesis, and erectile function. Given the impact of endothelial-derived nitric oxide (NO) in vascular biology, a great deal of research over the past decade has focused on the role of NO synthesis from the endothelium in normal erectile physiology as well as in disease states. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the occurrence of ED. Therefore, a likely target of gene therapy for the treatment of ED is eNOS. This communication reviews the role of eNOS in erectile physiology and discusses the alterations in eNOS expression in various vascular diseases of the penis. Putative gene therapy interventions to restore eNOS expression and subsequent endothelial function may represent an exciting new therapeutic strategy for the future treatment of ED.

Objective: To assess the accumulation of advanced glycation end products (AGEs) in streptozotocin (STZ)-induced diabetic rat cavernosal tissue, and to determine whether the protective effect of aminoguanidine (AG) on erectile function is related to the timing of treatment, as the accumulation of AGEs in the penis may be important in the pathogenesis of diabetes mellitus-induced erectile dysfunction, and prolonged treatment with AG (a selective AGE inhibitor), prevents erectile dysfunction in this situation., Materials and Methods: Harlan Sprague-Dawley rats were divided into groups 1-4, i.e. age-matched controls; STZ diabetic rats (60 mg/kg intraperitoneal) given free access to water; STZ diabetic rats treated with AG (1 g/L per day in the drinking water) immediately after inducing diabetes; and STZ-diabetic rats treated with AG 1 month after inducing diabetes, respectively. Two months after inducing diabetes the intracavernosal pressure was measured after cavernosal nerve stimulation, and cavernosal AGE (5-hydroxy methyl furfural, 5-HMF) levels assessed., Results: Cavernosal tissue 5-HMF levels from groups 2 and 4 were significantly higher than in group 1 (control). The expression of 5-HMF in group 3 was similar to that in group 1. Diabetic rats had significantly lower erectile function than controls, while groups 3 and 4 (treated with AG) had normal erectile function, as measured by cavernosal nerve stimulation., Conclusions: The effect of AG on AGE levels seems to be time-dependent; that the 1-month treatment with AG improved erectile function with no change in AGEs suggests that AG has protective effects on the penile vasculature through alternative pathways.

Purpose: Erectile dysfunction (ED) occurs in 20% to 54% of men with Peyronie's disease (PD). We investigated the role of vascular status in the pathophysiology of ED in patients with PD., Materials and Methods: A total of 509 consecutive men with PD (group 1--impotent 259, 1a, and potent 250, 1b, mean age +/- SD 54.6 +/- 4.4 years) and 507 consecutive men with ED only (group 2--mean age 49.4 +/- 12.4 years) underwent penile duplex ultrasonography (PDU). Detailed sexual and medical history, and focused physical examination were performed in all patients. Patients in the 2, groups were stratified according to age (18 to 80 years) and classified according to PDU results (normal vascular status, arterial insufficiency, veno-occlusive dysfunction [VOD] and mixed vascular pathology)., Results: VOD was observed in 23.1% and 42.8% of patients in groups 1 and 2, respectively (p <0.05). Although VOD was significantly more common in group 2 (ED alone) than in group 1a (PD plus ED) in the third decade (p <0.05), overall PDU results showed no statistical difference for VOD between these 2 groups (p >0.05). Of note, mixed vascular pathologies were significantly higher in group 1a than in group 2 in the third through fifth decades (p <0.05), while arterial insufficiency was more common in the seventh decade (p <0.05)., Conclusions: While many groups have investigated the vascular causes of ED, the exact etiology of ED in men with PD remains controversial. A possible relationship between ED and VOD in patients with PD has been previously reported. The current PDU study demonstrates that for all ages except 30 to 39 years the prevalence of VOD in patients with PD plus ED is similar to that of patients with ED alone.

Significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. RhoA/Rho-kinase may suppress endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that RhoA/Rho-kinase contributes to diabetes-related erectile dysfunction and down-regulation of eNOS in the streptozotocin (STZ)-diabetic rat penis. Colocalization of Rho-kinase and eNOS protein was present in the endothelium of the corpus cavernosum. RhoA/Rho-kinase protein abundance and MYPT-1 phosphorylation at Thr-696 were elevated in the STZ-diabetic rat penis. In addition, eNOS protein expression, cavernosal constitutive NOS activity, and cGMP levels were reduced in the STZ-diabetic penis. To assess the functional role of RhoA/Rho-kinase in the penis, we evaluated the effects of an adeno-associated virus encoding the dominant-negative RhoA mutant (AAVTCMV19NRhoA) on RhoA/Rho-kinase and eNOS and erectile function in vivo in the STZ-diabetic rat. STZ-diabetic rats transfected with AAVCMVT19NRhoA had a reduction in RhoA/Rho-kinase and MYPT-1 phosphorylation at a time when cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were restored to levels found in the control rats. There was a significant decrease in erectile response to cavernosal nerve stimulation in the STZ-diabetic rat. AAVT19NRhoA gene transfer improved erectile responses in the STZ-diabetic rat to values similar to control. These data demonstrate a previously undescribed mechanism for the down-regulation of penile eNOS in diabetes mediated by activation of the RhoA/Rho-kinase pathway. Importantly, these data imply that inhibition of RhoA/Rho-kinase improves eNOS protein content and activity thus restoring erectile function in diabetes.

Erectile dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to determine whether a combination of sildenafil and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats + sildenafil (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVbetagal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p. injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1-2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were assessed in the cavernosal tissue. STZ-diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were similar to control animals. STZ-diabetic rats administered sildenafil demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings, while the AUC was significantly increased at all voltage (V) settings. The increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at all V settings was greater than STZ-diabetic rats transfected with AdCMVbetagal. STZ-diabetic rats transfected with AdCMVeNOS and administered sildenafil had a significant increase in total ICP that was greater than eNOS gene therapy alone. Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but were increased after transfection with AdCMVeNOS to values greater than control animals. In conclusion, overexpression of eNOS and cGMP in combination with sildenafil significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats. Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene therapy alone.

The objective of this study was to evaluate the efficacy of topically applied prostaglandin E1 (PGE(1))+5% SEPA (soft enhancement of percutaneous absorption) on the glans penis in a feline erection model. Erectile response after glans penis administration of PGE(1)+5% SEPA cream (Topiglan, MacroChem Co., Lexington, MA, USA) was compared to the erectile response after intracavernosal administration of the triple-drug combination (1.65 mg papaverine, 25 microg phentolamine, and 0.5 microg PGE(1)). The placebo cream and increasing concentrations (0.25%, 2.5 mg/ml; 0.5%, 5 mg/ml; and 1%, 10 mg/ml) of PGE(1)+5% SEPA were applied in a total volume of 0.1 ml via a plastic needle-less syringe. The control triple-drug combination was administrated intracavernosally via a 30-gauge needle at the completion of each experiment to serve as a control reference. With each application of placebo, PGE(1)+SEPA, and the triple-drug combination, changes in intracavernosal pressure and systemic blood pressure were continuously monitored. Topical application of PGE(1)+SEPA induced increases in intracavernosal pressure in a dose-dependent manner, with minimal effects on systemic blood pressure. The increases obtained with 1% PGE(1) Topiglan cream were similar to the intracavernosal pressure values elicited by the standard intracavernosal triple-drug combination. These data demonstrate that topical glans penis application of PGE(1)+SEPA can induce an erectile response in cats with minimal systemic adverse effects. Oral pharmacological agents are the first-line treatment for male ED. Studies investigating the effectiveness of noninvasive modalities such as topical therapy should continue, because these agents have the potential to avoid the systemic effects commonly seen with oral therapies. Additionally, topical therapy may also benefit patients who are unresponsive to oral agents or have explicit contraindications. Topical PGE(1) application to the glans penis may become an important treatment option in selected patients suffering from erectile dysfunction.

Purpose: We investigated the relationship between penile curvature severity and co-morbidities in men with Peyronie's disease (PD) and assessed whether the severity of curvature had an impact on penile vascular status and/or erectile function., Materials and Methods: Based on a 10-year period 469 patients with PD were retrospectively evaluated in regard to age at diagnosis, type and degree of penile curvature, erectile dysfunction (ED) and other comorbidities, such as diabetes mellitus, hypertension, serum lipid abnormalities, smoking and ischemic heart disease. To assess penile vascular status all men with PD underwent penile duplex Doppler ultrasound evaluation. The severity of penile curvature was classified using the Kelami system, that is grade 1--curvature 30 degrees or less, grade 2--30 to 60 degrees and grade 3--greater than 60 degrees., Results: Mean patient age was 54.8 +/- 4.3 years (range 18 to 79) and the mean duration of symptoms was 24.8 +/- 13.7 months (range 3 to 120). The most common penile abnormality was dorsal curvature in 47.1% of patients. The most frequently documented co-morbid conditions in association with PD were hypertension in 27.2% of cases, smoking in 25.5%, hypercholesterolemia in 18.3%, diabetes mellitus in 17.2%, hyperlipidemia in 15.7% and a history of penile trauma in 13.2%. There was no relationship between the number or severity of each of these co-morbid conditions and the severity of the penile abnormality. In addition, there was no relationship between the severity of penile curvature and penile vascular status in patients with PD. Moreover, the prevalence of these comorbidities, except smoking and penile trauma history, was significantly higher in patients with PD and concurrent ED than in patients with PD only., Conclusions: While co-morbid conditions, such as hypertension, smoking, hypercholesterolemia, diabetes mellitus and hyperlipidemia, are commonly seen in patients with PD and may seem to be risk factors for PD, there was no statistical relationship between penile curvature severity and any of these comorbidities. Similarly there was no statistically significant relationship between the severity of curvature and penile vascular status or ED. The fact that the prevalence of associated comorbidities is higher in patients with PD and ED than in patients with PD only indicates that these comorbidities are more likely related to ED than to the pathogenesis of PD.

Purpose: Erectile dysfunction (ED) is frequently associated with diabetes mellitus. We determined if advanced glycation end products (AGEs) are involved in ED and investigated if the selective AGE and inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) could protect against the development of ED in a diabetic rat model., Materials and Methods: Harlan Sprague-Dawley rats were divided into 3 groups. The 9 nondiabetic rats in group 1 served as age matched controls. Diabetes was induced in the 9 rats in groups 2 and 3, respectively, by intraperitoneal injection of streptozocin (60 mg/kg). While group 2 was given free access to water and a standard diet, group 3 was treated with AG added to drinking water (1 gm/l daily). Two months after diabetes induction in vivo intracavernous pressure measurements were determined. Penile tissue glycation (furosine on high performance liquid chromatography), AGEs (pentosidine on high performance liquid chromatography and immunohistochemistry), AGE receptor (galectin-3 on immunohistochemistry and Western blot) and iNOS (Western blot) levels were measured in control and diabetic penises., Results: Cavernous tissue furosine, pentosidine, galectin-3 and iNOS protein levels were significantly elevated in the diabetic group compared with controls (p <0.05). On the other hand, cavernous tissue furosine, pentosidine, galectin-3 and iNOS expression were lower in diabetic rats treated with AG despite an unchanged glycemia level. Diabetic rats had a significant decrease in erectile function compared with control rats (p <0.05), while AG treated diabetic rats showed erectile function similar to that in control animals., Conclusions: Glycation, AGEs, galectin-3 and iNOS levels are elevated in diabetic rat penile tissue and significantly decreased by AG treatment. Furthermore, erectile function was preserved in AG treated animals. The observation that AG improved glycation despite no effect on glycemia suggests that AG may improve penile collagen turnover.

Surgical therapy for Peyronie's disease (PD) is reserved for patients with severe penile deformity that fails to improve with medical treatment and impedes sexual intercourse. The surgical treatment of PD consists of either correction of the penile deformity or insertion of a penile prosthesis in patients with concomitant erectile dysfunction (ED). Plaque incision/excision combined with grafting procedures or plication techniques are suitable in Peyronie's patients having an adequate penile vascular supply. When patients with Peyronie's disease have both penile deformity and ED, penile prosthesis implantation with or without excision or incision of the tunica is the current standard of care.

Objectives: To investigate the impact of advanced glycation end products (AGEs) and inducible nitric oxide synthase (iNOS) in chronic renal failure (CRF)-associated testicular dysfunction in an experimental model. In additionally, we examined whether different peritoneal dialysis (PD) fluids could contribute to the elevation in AGE level and iNOS expression in the testes., Methods: Adult male Wistar rats, 10 and 12 weeks of age and weighing 200-330 g, were divided into 5 groups. Group 1 served as the control group. In group 2, CRF was induced and a peritoneal catheter was implanted, but the dialysis procedure was not performed until the end of the study. In group 3, CRF was induced and PD was performed with dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF rats received dialysis fluids containing 3.86% glucose and icodextrin. Finally, an indwelling catheter was implanted and the dialysis procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin (group 5). Chronic PD began 4 weeks after insertion of the catheter. Each morning, this fluid was drained and 20 ml dialysis fluid, containing either 1.36 or 3.86% glucose, was given intraperitoneally for 4 h in unanesthetized animals. Each evening, 20 ml icodextrin was given for 10 h. The dialysis procedure was performed for 8 weeks. The AGE level was determined from the 5-hydroxymethyl-2-furaldehyde (5-HMF) content of penis samples and iNOS expression was assessed by immunohistochemistry., Results: The elevation of 5-HMF was significant in the testes from groups 2, 3, 4, and 5 when compared with group 1. Furthermore, the differences between groups 2 and 4, 3 and 4, and 4 and 5 were also significant (p < 0.05). Immunohistochemical analysis revealed the presence of iNOS predominantly in the Leydig cells. While iNOS staining was significantly lower in group 1 than in other groups, there were also significant differences between groups 2 and 3, 2 and 4, 2 and 5, 3 and 5, and 4 and 5 (p < 0.05). Finally, a significant statistical correlation was found between the 5-HMF and iNOS levels (r = 0.698, p = 0.001)., Conclusions: The present study identifies, for the first time, a potential role of AGE and iNOS in experimental CRF-associated testicular dysfunction. In addition, we found that PD fluids containing glucose contribute to this effect. These results may lead to a better understanding of the pathophysiological pathway in CRF-related testicular dysfunction., (Copyright 2003 S. Karger AG, Basel)

Objectives: To assess the long-term functional outcome, patient and partner satisfaction, and predictive factors for unfavorable results in men treated with a surgical approach for severe Peyronie's disease., Methods: Sixty-one patients underwent surgical treatment for Peyronie's disease between 1997 and 2001 and were retrospectively evaluated. All patients were assessed preoperatively with a detailed sexual and medical history, focused physical examination, and penile duplex ultrasonography. Nineteen patients underwent penile plaque excision/incision and grafting with Tutoplast cadaveric pericardial grafting material (group 1). Penile prosthesis implantation and manual modeling was performed in 31 patients (group 2a), and 11 men were treated with penile prosthesis implantation and pericardial grafting (group 2b)., Results: The mean follow-up of the patients was 21.9 +/- 13.6 months (range 12 to 48). Complete penile straightening was achieved in 15 patients (78.9%) in the excision/incision and grafting group. In the 42 men who underwent reconstruction using penile prosthesis implantation (group 2a,b), penile curvature resolved completely in 37 patients (88%). Long-term postoperative residual curvatures greater than 30 degrees occurred in 3 patients (15.7%) and 2 patients (4.8%) in groups 1 and 2a,b, respectively. One penile prosthesis (2.3%) was explanted in the second group for erosion. Patient responses to our questionnaire showed that overall 83.6% of the patients and 76.9% of the partners were satisfied with the surgical result., Conclusions: According to the results of this long-term, retrospective study, pericardial grafting can be used successfully after plaque excision/incision procedures in men undergoing surgical treatment for severe Peyronie's disease. In patients with Peyronie's disease and erectile dysfunction, implantation of a penile prosthesis and correction of the curvature with a graft can provide an acceptable, functionally straight penis without any increased risk of complications compared with penile prosthesis implantation alone.

Purpose: We determined whether adenoviral gene transfer of endothelial nitric oxide synthase (eNOS) to the penis of streptozotocin induced diabetic rats could improve the impaired erectile response., Materials and Methods: Two experimental groups of animals were transfected with adenoviruses, including streptozotocin (Sigma Chemical Company, St. Louis, Missouri) diabetic rats with AdCMVbetagal and streptozotocin diabetic rats with AdCMVeNOS. At 1 to 2 days after transfection these study animals underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age matched control rats. In control and transfected streptozotocin diabetic rats eNOS and neuronal NOS (nNOS) were examined by Western blot analysis. Constitutive and inducible NOS activities were evaluated in the presence and absence of calcium by L-arginine to L-citrulline conversion and nitrate plus nitrite levels were measured. In control and streptozotocin diabetic penes beta-galactosidase activity and localization were determined., Results: After transfection with AdCMVbetagal beta-galactosidase was localized to the endothelium and smooth muscle cells of the streptozotocin diabetic rat penis. Streptozotocin diabetic rats had a significant decrease in erectile function, as determined by peak and total intracavernous pressure (area under the curve) after cavernous nerve stimulation compared with control rats. Streptozotocin diabetic rats transfected with AdCMVeNOS had peak intracavernous pressure and area under the curve similar to those in control animals. This change in erectile function was a result of eNOS over expression with an increase in eNOS protein expression and constitutive NOS activity as well as an increase in nitric oxide biosynthesis, as reflected by an increase in cavernous nitrate plus nitrite formation. There was no change in nNOS protein expression or calcium independent conversion of NOS (inducible NOS activity)., Conclusions: Adenoviral gene transfer of eNOS significantly increased peak and total intracavernous pressure to cavernous nerve stimulation in streptozotocin diabetic rats to a value similar to the response observed in control rats. Our results suggest that eNOS contributes significantly to the physiology of penile erection. These data demonstrate that in vivo adenoviral gene transfer of eNOS can physiologically improve erectile function in the streptozotocin diabetic rat.

Objectives: To devise a set of clinical criteria that would identify which penile abnormality could be malignant and warrant biopsy, between Peyronie's disease (a pathological fibrosis involving the tunica albuginea of the penis) and epithelioid sarcoma (ES) of the penis (a rare malignant condition which can resemble Peyronie's disease in clinical presentation)., Patients and Methods: The pathology reports and histological slides of men with Peyronie's disease who underwent penile biopsy were reviewed for ES. The medical charts of suspicious cases were then reviewed by a pathologist, unaware of the origin, for consistencies in signs, symptoms and clinical findings. These consistencies were then to be used to develop criteria for biopsy. Thirty-two men underwent penile biopsy from 1992 to 2001., Results: Because there were no actual cases of ES, a specific set of criteria for ES could not be established. A review of previously published cases was then used for comparison with the present patients., Conclusions: Many of the previously reported cases included signs and symptoms of urethral narrowing or compression, causing lower urinary tract symptoms. In addition, the penile nodule size was reported to progressively enlarge over time. Because of the high prevalence of Peyronie's disease and low prevalence of ES, biopsy of every penile nodule is not judicious. However, signs and symptoms of urethral obstruction, and a progressively growing and persistently painful nodule should suggest a possible malignancy and warrant biopsy.

Objective: To describe our experience of inguinal exploration in patients who had a reasonable chance of having a benign testicular lesion., Patients and Methods: From 1995 to 2002, 11 patients (mean age 43 years, range 27-63) with testicular masses that were suspected to be benign underwent inguinal exploration., Results: In nine of the 11 patients, frozen-section analysis and the final pathological results were similar, and two underwent inguinal orchidectomy. In seven patients the testicle was spared. Finally, because of an uncertain pathological diagnosis and patient age, two patients underwent orchidectomy., Conclusions: Inguinal exploration and testicular-sparing surgery are reasonable options in patients with peripheral intratesticular lesions, on the basis of preoperative ultrasonographic characteristics, and if there is a possibility of the mass being benign because of age, race, physical examination and tumour markers.

The etiologies of erectile dysfunction (ED) after nerve-sparing radical prostatectomy have not been clearly elucidated. The aim of this study was to evaluate the effects of cavernous nerve injury on cavernous fibrosis, and to consider measures to prevent irreversible damage to the cavernous tissues. Twenty male Sprague-Dawley rats constituted the study population. The animals were divided into 2 groups; group 1 consisted of sham-operated rats (n = 10), and group 2 consisted of rats that underwent incision of both cavernous nerves (n = 10). Three months later, all rats underwent intracavernous papaverine injection (300 and 600 mg), and intracorporal pressures were recorded. Transforming growth factor-beta(1) (TGF-beta(1)) messenger RNA (mRNA) expression from rat penile tissue was measured using reverse transcriptase-polymerase chain reaction. Hypoxia-inducible factor-1alpha (HIF-1alpha), TGF-beta(1), and collagen I and III protein expressions were determined by Western blot analysis and immunohistochemical staining. Erectile function as studied with intracavernosal papaverine injection and histological analysis of penile cross-sections at 3 months was similar in both groups. TGF-beta(1) mRNA expression, HIF-1alpha, TGF-beta(1), and collagen I and III protein expressions were significantly greater in the neurotomy group. Immunohistochemical staining for TGF-beta(1), HIF-1alpha, and collagen III were qualitatively more positive in the neurotomy group, whereas collagen I staining was similar. This study demonstrates an increase in TGF-beta(1), HIF-1alpha, and collagen III synthesis in rat cavernosal smooth musculature after cavernous neurotomies. In theory, cavernous fibrosis may be reduced by employing various vasoactive agents or interventions that increase oxygenation to the corporal tissues during the postoperative period.