Effect of Oltipraz on urethral healing: An experimental study.

BACKGROUND: We aimed to examine the oral and topical effect of Oltipraz (OPZ) on fibrosis and healing after urethra injury in a rat model. METHODS: In all, 33 adult Sprague-Dawley rats were divided randomly into 5 different groups: sham, urethral injury group (UI), oral Oltipraz treatment group for 14 days after urethral injury (UI+oOPZ), intraurethral Oltipraz treatment group for 14 days after urethral injury (UI+iOPZ) and only intraurethral Oltipraz treatment for 14 days without urethral injury (sham+iOPZ). Pediatric urethrotome blade was used to create the urethral injury model for the injury groups (UI, UI+oOPZ and UI+iOPZ). After 14 days of treatment, all rats were sacrificed after penectomy under general anesthesia. Urethral tissue was evaluated histopathologically for congestion, inflammatory cell infiltration and spongiofibrosis, and immunohistochemically for transforming growth factor Beta-1 (TBF) and vascular endothelial growth factor receptor2 (VEGFR2). RESULTS: The congestion score was not statistically significantly different between the groups. Spongiofibrosis was distinctive in UI group and OPZ given groups. Inflammation and spongiofibrosis score were statistically significantly higher in the sham+iOPZ group compared to the sham group (P<0.05). VEGFR2 and TGF Beta-1 scores were statistically significantly higher in the sham+iOPZ group compared to the sham group (P<0.05). We did not find beneficial effect of OPZ on urethral healing. We found the harmful effect of intraurethral administration of OPZ in the group without urethral injury in compared to sham. CONCLUSIONS: According to our results, we cannot suggest OPZ in the treatment of urethral injury. Future studies in this area are needed.

Effect of Nintedanib on healing and fibrosis in rats with experimentally induced urethral injury.

AIM: We aimed to determine the effectiveness of Nintedanib treatment, which has known antifibrotic effect, in preventing fibrosis after urethral trauma. MATERIAL AND METHODS: Twenty-three adult Sprague-Dawley rats were divided randomly into 3 different groups: Sham, Urethral injury group (UI) and Urethral injury+ Nintedanib (UI+N). The urethral injury model was made with a pediatric urethrotome knife. Nintedanib was administered at a dose of 50mg/kg by oral gavage for 14 days at the same time every day. After 14 days of treatment, all rats were performed penectomy under general anesthesia. Urethral tissue was evaluated histopathologically (congestion, inflammatory cell infiltration and spongiofibrosis) and immunohistochemically (transforming growth factor (TBF) Beta-1 and vascular endothelial growth factor receptor 2 (VEBFR2)). RESULTS: Histopathological findings: Group UI had higher scores in all categories (congestion, inflammatory cell infiltration, and spongiofibrosis), followed by Group UI+N and Group Sham, respectively. A statistically significant difference was found between Group UI and Group UI+N in terms of the scores of histopathological parameters (p<0.05). Immunohistochemical findings: Group UI had higher scores in both categories, followed by Group UI+N and Group Sham, respectively. A statistically significant difference was found between Group UI and Group UI+N in TGF Beta-1 and VEGF scores (p<0.05). CONCLUSION: We found that Nintedanib administration after urethral trauma reduced inflammation and fibrosis histologically and immunohistochemically. The positive effect of Nintedanib on inflammation and fibrosis after urethral trauma reported in this animal study is encouraging for a potential clinical human application.

Effects of taking tadalafil 5 mg once daily on erectile function and total testosterone levels in patients with metabolic syndrome.

We aimed to evaluate the efficacy of tadalafil 5 mg once-daily treatment on testosterone levels in patients with erectile dysfunction (ED) accompanied by the metabolic syndrome. A total of 40 men with metabolic syndrome were evaluated for ED in this study. All the patients received 5 mg tadalafil once a day for 3 months. Erectile function was assessed using the five-item version of the International Index of Erectile Function (IIEF) questionnaire. Serum testosterone, follicle-stimulating hormone and luteinising hormone levels were also evaluated, and blood samples were taken between 08.00 and 10.00 in the fasting state. All participants have three or more criteria of metabolic syndrome. At the end of 3 months, mean testosterone values and IIEF scores showed an improvement from baseline values (from 3.6 ± 0.5 to 5.2 ± 0.3, from 11.3 ± 1.9 to 19 ± 0.8 respectively). After the treatment, serum LH levels were decreased (from 5.6 ± 0.6 to 4.6 ± 0.5). There was significantly difference in terms of baseline testosterone and luteinising hormone values and IIEF scores (p < .05). Based on our findings, we recommend tadalafil 5 mg once daily in those men with erectile dysfunction especially low testosterone levels accompanied by metabolic syndrome.

Calcium signalling and ER stress in insulin resistance and atherosclerosis.

The burden of type 2 diabetes and its major complication cardiovascular disease is rapidly increasing worldwide. Understanding the underlying pathogenic mechanisms of these diseases is crucial to develop novel therapeutics. Recent work using genetic and biochemical methods in mouse models and human samples have identified disturbed calcium signalling and endoplasmic reticulum stress as emerging factors involved in the pathogenesis of many metabolic diseases. In this review, we will highlight the specific roles of calcium signalling and endoplasmic reticulum stress response in the development of insulin resistance and atherosclerosis.

Combination therapy with selective serotonin reuptake inhibitors and phosphodiesterase-5 inhibitors in the treatment of premature ejaculation.

We aimed to evaluate the effectiveness of paroxetine and tadalafil combination in the treatment of premature ejaculation (PE). A total of 150 primary (lifelong)PE patients were randomly distributed into three groups of 50 patients each. Group 1 received 20 mg paroxetine every day for 1 month, Group 2 received 20 mg tadalafil on demand 2 h before intercourse, and Group 3 received paroxetine and tadalafil on demand 2 h before intercourse. Intravaginal ejaculatory latency times (IELT) scores were evaluated at baseline, at the end of the first month of therapy and 1 month after discontinuation of the treatment, while International Index of Erectile Function (IIEF) questionnaire scores were evaluated both prior to and after the treatment. At the end of the first month of therapy, IELT scores were compared with the basal values and statistically significant changes were detected (60.6 ± 30.2-117.3 ± 67.3, 68.5 ± 21.4-110.2 ± 37.3, 71.56 ± 40.23-175.2 ± 60.2)(P < 0.01). IELT scores after discontinuation of treatment were found to be close to the baseline IELT scores (P > 0.05). IIEF scores were evaluated both prior to and after the treatment, and no statistically significant difference was detected (P > 0.05). It is concluded that utilisation of selective serotonin reuptake inhibitors (SSRI) and phosphodiesterase-5 inhibitors (PDE5i) combination before intercourse seems to provide significantly longer ejaculatory latency times as compared with SSRI alone for a long time in patients with PE.

Relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors treatment on premature ejaculation: decreased nitric oxide is associated with premature ejaculation.

The aim of the present study was to determine the relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors (SSRI) treatment on premature ejaculation. Sixty married men (aged 20-50) with lifelong premature ejaculation and forty healthy men (aged 24-48) as control group were included in this study. The patients were evaluated by intravaginal ejaculation latency time (IELT) for premature ejaculation (PE). IELT<1 min is accepted PE. Patients with diabetes mellitus, chronic disorders or erectile dysfunction and heavy smokers were excluded. All patients were evaluated with history, physical examination, International Index of Erectile Dysfunction-5 (IIEF-5) score and IELT by stopwatch method. Nitric oxide levels were measured by Griess reaction, and all samples were frozen at -80 °C. Patients were randomly categorised 4 group to receive fluoxetine 20 mg day(-1) (Group 1), paroxetine 20 mg day(-1) (Group 2), sertraline 50 mg day(-1) (Group 3) and healthy control (Group 4) for 4 weeks. Baseline and post-treatment findings were compared between the four groups. At the end of 4 weeks, in fluoxetine, paroxetine, sertraline groups mean IELT values showed a statistically significant improvement from the baseline values (P < 0.001, P < 0.001, P = 0.03; respectively). Baseline and 1st month follow-up mean IIEF scores were 24.5 and 23.05, 24.70 and 23.60 (P < 0.05) in group 1 and group 3 respectively; also 23.09 and 23.32 (P > 0.05) in group 2. Baseline serum NO levels were 31.8, 30.44, 30.8 and 42.84 in fluoxetine, paroxetine, sertraline and healthy control groups respectively. NO levels were statistically lower in patients with PE. After treatment of fluoxetine, paroxetine and sertraline, NO levels were increased baseline (35.8, 36.4, 38.08) (P < 0.05). Our findings indicated that PE is associated with decreased serum NO levels. After the SSRI treatment increased, NO may retard ejaculation presumably by central peripheral mechanism. Further studies are needed to confirm this suggestion and the role of NO in pathophysiology and treatment for premature ejaculation.