The therapeutic effect of ALT-711 on erectile function in rats treated with high-level AGEs (advanced glycation end products) containing diet.

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.

Semen analysis in adolescents with familial Mediterranean fever.

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.

Prevalence of male pelvic dysfunction: results from the Turkish society of andrology male sexual health study group.

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.

Usage of neck circumference as novel indicator of erectile dysfunction: a pilot study in Turkish population.

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.

Effect of abamectin exposure on semen parameters indicative of reduced sperm maturity: a study on farmworkers in Antalya (Turkey).

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.

Therapeutic effect of combination of alagebrium (ALT-711) and sildenafil on erectile function in diabetic rats.

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.

Relationship between mast cell and iNOS expression in testicular tissue associated with infertility.

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.

Feline penile erection induced by topical glans penis application of combination alprostadil and SEPA (Topiglan).

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.

Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats.

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.

Surgical approaches for advanced Peyronie's disease patients.

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.

Penile epithelioid sarcoma and the case for a histopathological diagnosis in Peyronie's disease.

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.

Testicular-sparing surgery: a reasonable option in selected patients with testicular lesions.

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.

Penile scintigraphy with 99mTc-human immunoglobulin G: a novel method for distinguishing the unstable and stable phases of Peyronie's disease.

OBJECTIVE: To investigate the value of penile scintigraphy using 99mTc-human immunoglobulin G (IgG) to differentiate the unstable (acute) and stable (chronic) phases of Peyronie's disease (PD). PATIENTS AND METHODS: Thirty-two consecutive patients (25 with PD and seven without) were evaluated using a detailed sexual history, serum chemistry panel, colour Doppler ultrasonography during simultaneous intracavernosal injection of 50 mg papaverine and stimulation, and 99mTc-IgG scanning. When indicated, nocturnal penile tumescence monitoring, dynamic infusion cavernosometry, cavernosonography and cavernosal artery systolic occlusion pressure were measured. After administering 370 MBq of 99mTc-IgG, images were taken at 30 min, 1, 2, 3 and 4 h. The scans were considered positive if there was any focal accumulation of radiopharmaceutical consistent with PD plaque formation. RESULTS: Eleven of the 25 patients with PD (mean age 56 years, sd 8) were in the unstable phase, the remaining 14 being in the stable phase. There was a localized increase in 99mTc-IgG activity in 10 patients who had unstable PD. There was complete resolution of increased activity in two patients at 12 and 13 months of follow-up. Of the 14 patients in the stable phase, 12 (at > 1 year) showed neither increased nor decreased 99mTc-IgG activity. In the remaining two patients there was increased activity on the plaque side. There was no local increase in activity in the control group. CONCLUSION: Inflammatory reactions can develop at various intervals during the unstable phase of PD. Medical methods should be used during the unstable phase and surgery delayed until the stable phase of the disease begins. An objective method of differentiating between the phases is therefore important. Penile 99mTc-IgG imaging is a new diagnostic approach for confirming the unstable phase of PD.

Impact of chronic renal failure and peritoneal dialysis fluids on advanced glycation end product and iNOS levels in penile tissue: an experimental study.

OBJECTIVES: To investigate the impact of chronic renal failure (CRF) on advanced glycation end product and inducible nitric oxide synthase (iNOS) in penile tissue, we examined the advanced glycation end product 5-hydroxy methyl furfural (5-HMF) content and iNOS expression in rats in which uremia had been produced by greater than 85% nephrectomy. In addition, the contribution of peritoneal dialysis (PD) fluids to the elevation of penile tissue 5-HMF levels and iNOS staining scores has been investigated. METHODS: Adult male Wistar rats, aged between 10 and 12 weeks and weighing 200 to 330 g, were divided into five groups that each included 6 animals. The first group served as a control group. In the second group, CRF was induced and a peritoneal catheter was implanted, but PD was not performed. In group 3, CRF was induced and PD was performed using dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF was also induced and PD was performed using 3.86% glucose and icodextrin. Finally, in group 5, without CRF, an indwelling catheter was implanted, and the PD procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin. RESULTS: The elevation in 5-HMF levels and iNOS staining scores in penile tissue from groups 2, 3, 4, and 5 was significant compared with group 1 (P <0.05). The elevation in 5-HMF levels and iNOS staining scores was also significant between groups 2 and 3, 2 and 4, 3 and 4, 3 and 5, and 4 and 5 (P <0.05). Moreover, the correlation between the 5-HMF levels and iNOS staining scores was statistically significant (r = 0.525, P = 0.003). CONCLUSIONS: In the present experimental study, we found that 5-HMF levels and iNOS staining scores were significantly elevated in rat penile tissue in which uremia had been produced compared with the groups without CRF. Additionally, PD fluids containing glucose had an effect on the elevation of penile tissue 5-HMF levels and iNOS staining scores.

Honeymoon impotence: psychogenic or organic in origin?

OBJECTIVES: Honeymoon impotence is the inability to perform successful sexual intercourse during the initial experience, especially during the first nights of marriage, and it is relatively frequent in Turkey. We investigated the underlying penile vascular abnormalities in patients presenting with honeymoon impotence and sought to differentiate between psychogenic and organic etiologies. METHODS: Between 1989 and 1999, 90 patients sought urologic help for honeymoon impotence. Patient age ranged from 18 to 39 years (mean 28.06 +/- 3.4). All patients were given an intracavernous injection of 60 mg papaverine combined with self-manual genital stimulation (CIS test) to assess the degree of tumescence. Patients with a positive response to the CIS test were later evaluated with nocturnal penile tumescence (NPT) monitoring. Patients with a negative response to the CIS test and/or NPT monitoring were evaluated further using penile color Doppler ultrasound. RESULTS: A psychogenic etiology was found in 61 patients (67.7%), 50 (55.5%) of whom achieved satisfactory sexual intercourse after intracavernous injection. Twenty-five patients (27.7%) exhibited penile vascular abnormalities by color Doppler ultrasound. Neurogenic erectile dysfunction was considered in the remaining 4 patients (4.4%) with a positive response to the CIS test, abnormal findings on NPT monitoring, and a normal vascular system with color Doppler ultrasound. CONCLUSIONS: The present study is the first to report penile vascular abnormalities in patients presenting with honeymoon impotence, which was previously believed to be exclusively psychogenic in origin. The evaluation of the penile vascular system in patients with honeymoon impotence may reveal underlying penile vascular abnormalities, allowing the choice of the appropriate therapeutic option.