Levent Ozcan

Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population

We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the chi2-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P<0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences.

Interobserver variability in Gleason histological grading of prostate cancer

Abstract Objective: The aims of this study were to evaluate the reproducibility of the Gleason grading system and to compare its interobserver variability with the novel Gleason grade grouping proposal using a large sample volume. Materials and methods: In total, 407 pathology slides of prostate needle biopsies from 34 consecutive patients with prostate cancer were re-evaluated. The International Society of Urological Pathology 2005 modified Gleason grading system with Epstein’s modification was used. Two pathologists, blind to each other and to the initial pathology report, performed the pathological evaluation. To determine interobserver concordance, the kappa (κ) coefficient test was used. Results: Pathologist 1 and pathologist 2 detected a tumor in 202 and 231 cores, respectively (p < 0.001). The two pathologists disagreed on the presence of a tumor in 31 cores. Of these 31 cores, 74% (n = 23/31) were Gleason pattern 3. The mean length of the cancer foci in these 31 disputed cores was 1.54 ± 0.8 mm. Concordance rates between the two observers for primary and secondary Gleason patterns were 63.96% (κ = 0.34) and 63.45% (κ = 0.37), respectively. Concordance with respect to the Gleason sum was 57.9% (κ = 0.43). When the Gleason scores were classified into the novel Gleason grade grouping, concordance was found to be 51.7% (κ = 0.39). Conclusions: The agreement between observers on the Gleason sum was moderate. The novel Gleason grade grouping did not improve interobserver agreement. Further studies are needed to confirm these results on interobserver variability.

Urolithiasis is associated with low serum testosterone levels in men

OBJECTIVE To evaluate the relationship among urolithiasis, metabolic syndrome (MetS) and serum testosterone (T) level in men. MATERIAL AND METHODS 513 men older than 18 years were enrolled in this study: 313 of the subjects had a history of stones (group 1) and 200 had no history of stones (controls, group 2). Early morning T levels were recorded and anthropometric measurements were investigated to evaluate MetS. Analyses were completed using chi-square tests. RESULT Serum T level was lower in stone forming patients than control subjects and 161 (%51.4) men in group 1 and 92 (%46) men in group 2 were diagnosed with metabolic syndrome. T level was found lower limit (< 285 ng/dl) in the MetS and urolithiasis group (p 0.002, OR 2.71). CONCLUSIONS We found low testosterone levels in the patients with stone disease and prevalence of the MetS in men with urolithiasis was higher than in men without stone disease. Our findings show that levels of testosterone had no effect on stone formation, but the factors that cause stone formation can have an effect on the level of testosterone.

Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the χ2-test. RESULTS: The short (S) allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (p<0.05). Out of the 69 total PE patients, 41 patients (59%) responded to therapy. There was no significant difference in the International Index of Erectile Function score at the end of therapy between the responder and nonresponder groups. The frequencies of the L allele and S allele were 20% and 39%, respectively, in the responder group (p<0.05). CONCLUSION: We conclude that premature ejaculation patients with the SS genotype respond well to selective serotonin reuptake inhibitor therapy. Further studies with large patient groups are necessary to confirm this conclusion.

Effects of Tadalafil 5 mg Dosed Once Daily in Men with Premature Ejaculation

Purpose: In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). Methods: Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. Results: The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. Conclusion: We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE.

Beneficial effects montelukast, cysteinyl-leukotriene receptor antagonist, on renal damage after unilateral ureteral obstruction in rats

Introductıon Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO) in rats. Mateirıals and Methods 32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide(NO), malondialdehyde(MDA) and reduced glutathione(GSH) levels were determined in the other part of kidneys. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p<0.005). Also, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in group 3 compared the other groups(p<0.005). Conclusıon We can say that montelukast prevent kidney damage with antioxidant effect, independently of NO.

TT polymorphism in rs2165241 and rs1048661 region in lysyl oxidase like-1 gene may have a role in stress urinary incontinence physiopathology

Aim:  In experimental studies, lysyl oxidase like‐1 (LOX‐L1) (−/−) mice were shown to have similar pelvic floor dysfunction to female rats. LOX‐L1 levels in endopelvic fascia decrease as a result of increasing births in women with pelvic prolapse. For these reasons, we investigated the LOX‐L1 gene polymorphism, which has an important role in connective tissue and collagenous metabolism in stress urinary incontinence (SUI).

Association of erectile dysfunction and urolithiasis

OBJECTIVES In recent years, it has been shown that there is association between metabolic syndrome and urinary stone disease. Stone disease and erectile dysfunction (ED) are considered as systemic diseases which are associated with hormonal and metabolic disorders. Therefore we investigated the relationship between ED and urinary tract calculi. MATERIAL AND METHODS 98 male patients with urolithiasis and 59 randomly selected male patients without stone disease were included in the study. Serum testosterone (T) levels were measured and International Index of Erectile Function (IIEF)-15 questionnaire forms were used to assess ED. RESULTS The prevalence of ED was found 29% (29 patients) in the urolithiasis group. Sixty-nine patients (71%) had no ED; 16 (16.3%) had mild, 5 (5.1%) had moderate and 8 (8.2%) had severe ED. None of the patients in the control group had severe or modarete ED, six patients (10.2%) had mild ED. Serum T levels were detected at the level of biochemical hypogonadism on 13 patients with stones (13.3%) and T levels were detected at the lower limit in 18 (18.3%) patients. CONCLUSION In our study we have shown that ED and low T levels are significantly associated with urolithiasis. We propose that the patients with urolitiasis should be evaluated for ED and hypogonadism.

Comparison of the clinical parameters of benign prostate hyperplasia in diabetic and non diabetic patients

OBJECTIVE We evaluated the correlation between benign prostate hyperplasia (BPH) measures and diabetes mellitus in men with benign prostate hyperplasia in a prospective study. MATERIALS AND METHODS Between 2008-2012, 100 diabetic and 200 non diabetic patients undergoing surgery due to benign prostate hyperplasia were enrolled in the study. The parameters evaluated for each patients included prostate volume, fasting blood glucose, HbA1c, total testosterone, total prostatic specific antigen (T-PSA), triglicerides, total cholesterol and body mass index (BMI). A questionnaire including international prostate symptom score (IPSS) was sdministered and uroflow test measuring the peak urinary flow rate was performed to appreciate the complaints of the patients objectively. RESULTS Diabetic patients are more likely to have larger prostate volume. The symptom score evaluated by IPSS and post micturition residual volume were also significantly higher in diabetic groups. The other statistically significant different parameter between two groups was total testosterone that diabetic patients tend to have lower levels. Diabetic counterparts were established to have higher BMI. No statistically significant differentiation was observed about trigliceryde and total cholesterol levels and uroflow rates. CONCLUSIONS Our study suggests a positive correlation between high prostate volume and diagnosis of diabetes mellitus in patients with benign prostatic hyperplasia. We also observed a positive correlation between symptom scores and post micturion residual volumes and diagnosis of diabetes mellitus suggesting that the presence of diabetes is related to both static and dynamic components of benign prostate hyperplasia. Additionally testosterone levels were lower in diabetic patients. Further studies need to confirm these relationship in a larger population.

Low serum insulin-like growth factor-1 in patients with erectile dysfunction.

ObjectiveEndothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED.Materials and methodsAll men were evaluated for ED and divided into two groups: 80 patients suffering from ED for > 1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated.ResultsThe mean age of patients in ED group was 60.4 ± 11.3 years and 55.4 ± 9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5 ± 38.3 and 132.5 ± 53.3 ng/ mL, respectively, P < 0.001). The IGF-1 levels were positively correlated with ED score (r = 0.623, P < 0.01).ConclusionIn this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population.RésuméObjectifsLa dysfonction endothéliale et les altérations vasculaires jouent un rôle crucial dans la pathogenèse de la dysfonction érectile (DE). L’Insulin-like Growth Factor-1 (IGF-1) est l’un des facteurs de croissance qui ont un vaste champ d’effets biologiques. IGF-1 est un médiateur important de la croissance, différentiation et transformation cellulaires dans différents tissus. Le but de la présente étude était de rechercher une association entre les taux d’IGF-1 et la dysfonction érectile.Matériel et MéthodesLa dysfonction érectile a été évaluée chez tous les hommes, constitués en 2 groupes : 80 patients souffrant de DE depuis plus d’un an, et 80 sujets sans DE recrutés comme groupe témoin dans l’étude. Le diagnostic de DE était basé sur le score 5 de l’Index International de la Fonction Erectile. Les taux d’IGF-1 ont été mesurés par immunodosage automatisé par chemiluminescence. La relation entre les taux d’IGF-1 et le score de la DE a été statistiquement évaluée.RésultatsL’âge moyen des patients du groupe DE était de 60.4±11.3 ans et de 55.4±9.6 dans le groupe témoin. Les taux plasmatiques d’IGF-1 étaient significativement plus bas dans le groupe DE que chez les témoins (respectivement 96.5±38.3 et 132.5±53.3 ng/mL, P < 0.001). Les taux d’IGF-1 étaient positivement corrélés au score de la DE (r = 0.623, P < 0.01).ConclusionsNos résultats indiquent que les taux sériques d’IGF-1 sont associés à une dysfonction endothéliale qui prédit la DE. L’IGF-1 sérique apparaît être un prédicteur spécifique de la DE, et il pourrait être utilisé pour une prédiction précoce de la DE dans la population masculine.