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.

Evaluation of MicroRNA-124 Expression in Renal Cell Carcinoma.

The Wingless/INT (WNT) signaling network has roles in renal cancer development. It was shown that the tumor-suppressor microRNA-124 (miR-124) is associated with the Wnt pathway. Thus, we aimed to measure miR-124 expression levels to evaluate whether it is a prognostic marker or a potential treatment strategy. Thirty tumor and 30 surrounding healthy kidney tissues from the same subjects diagnosed with renal cell carcinoma (RCC), were included in the study. The expression levels of miR-124 were measured with real-time polymerase chain reaction (qPCR) and determined by the 2-ΔΔCT method. The Statistical Package for Social Science (SPSS) version 22 program was used for statistical analyses and a p value of 0.05 was considered to be statistically significant. The expression levels of miR-124 was found to be about 3-fold lower in tumors than in healthy tissues (p 0.001) and decreased expression levels correlated with tumor stage, tumor diameter, body mass index (BMI) and neutrophil values (p 0.05). Our results showed that miR-124 expression levels are associated with RCC. MicroRNA-124 may be assessed as a biomarker in prognosis and the restoration of miR-124 expression might be effective in the treatment of RCC.

The role of inflammatory parameters (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-eosinophil ratio) in patients with Peyronie's disease.

OBJECTIVES: The aim of the study was to investigate the ability of the systemic inflammatory parameters to predict the discrimination of the phases of Peyronie's disease (PD). MATERIALS AND METHODS: Demographic, clinical, and laboratory data from 156 patients with PD were analyzed. A complete blood count (CBC) was obtained for every patient, and the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-eosinophil ratio (MER) were calculated for every men. Subsequently, patients were divided into two groups based upon the phase of the disease. RESULTS: The mean age was 51.9 ± 9.6 in all study population. The mean duration between symptom onset and patient evaluation was 4.2 ± 3.2 months in acute phase group, while it was 32.7 ± 31.7 months in chronic phase group (p < 0.001). There were no significant differences between the groups according to comorbidities such as diabetes, hypertension, lipid abnormalities, ischemic heart disease, smoking, and alcohol consumption. There was a statistically significant difference in NLR and PLR between two groups (p = 0.008, p = 0.008, respectively). NLR and PLR were significantly correlated with discrimination status in univariate analysis (p = 0.003, p = 0.005, respectively). Multivariate regression analysis revealed that NLR was the only independent risk factor for discrimination of the phases of PD (p < 0.001). The ROC analysis revealed a cutoff value of 1.8 (AUC 0.712, p < 0.001; sensitivity 61.1%; specificity 75.0%) for the NLR. CONCLUSION: Our study demonstrated that NLR could be helpful to differentiate the chronic phase from the acute phase in patients with PD. Therefore, NLR could be used as an objective biomarker to the management of the disease and choosing the appropriate treatment.

Protective effect of hydrogen sulfide on experimental testicular ischemia reperfusion in rats.

AIM: Testicular torsion is an urgent urological condition. Ischemia-reperfusion (I/R) processes that occur after detorsion as a treatment for torsion are caused by testicular injury. The purpose of our study is investigating the protecting effect of hydrogen sulfide (H2S) on the testicular ischemia reperfusion injury. MATERIALS AND METHODS: Thirty-eight Wistar-Albino rats were divided randomly into 6 different groups: Control (6); sham (6); IR-E (6)-2 h of torsion and 4 h of reperfusion; IR-E + H2S (6)-in addition to the IR-E group, 75 µmol/kg of sodium hydrogen sulfide (NaHS) was administered intraperitoneally 30 min before reperfusion; IR-L (7)-2 h of torsion and 24 h of reperfusion; IR-L + H2S (7)-in addition to the IR-L group, 75 µmol/kg NaHS was administered intraperitoneally 30 min before reperfusion. Biochemically, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), reductive glutathione (GSH), and tumor TNF-α levels were measured in the testis. Serum TNF-α levels were also measured. Hematoxylin and eosin (H & E) was used for histopathological staining and microscopic findings were examined. The Johnsen score was performed to assess spermatogenesis activity in the testis. Apoptosis protease activating factor-1 (Apaf-1) and inducible nitric oxide synthase (iNOS) activity were evaluated immunohistochemically as well. Statistical analyses were made by the Chi-squared test and one-way analysis of variance. RESULTS: MDA and NO levels were significantly increased in the IR-L group compared with sham and which decreased by the addition of H2S treatment to the IR-L group (p < 0.05) in biochemical evaluation. GSH vs SOD levels were decreased in the IR-L group compared with sham and which increased by the addition of H2S treatment to the IR-L group, but this correlations were not statistically significant (p > 0.05). Tissue and serum TNF-α levels were significantly increased in the IR-E group compared with sham and which decreased by the addition of H2S treatment to the IR-E group. Johnsen score was the lowest in IR-L group (p < 0.05). Apaf-1 and iNOS activity were significantly increased in the IR-L group compared with sham and which decreased by the addition of H2S treatment to the IR-L group (p < 0.05) in immunohistochemical evaluation. CONCLUSIONS: First, the authors would like to say that H2S treatment is protective and it is against ischemia reperfusion injury in testicular torsion. The anti-inflammatory, antioxidant, and antiapoptotic properties of H2S caused protective effect as shown in this study.

Protective effect of nebivolol on gentamicin-induced nephrotoxicity in rats.

OBJECTIVE: Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. As we know, treatment with nebivolol has been shown to decrease renal fibrosis and glomerular injury as well as improve endothelial dysfunction. Therefore, we evaluated the potential protective effect of nebivolol (NBV) against GEN-induced nephrotoxicity in rats. MATERIAL AND METHOD: Twenty-four rats were randomly divided into four groups: control group (Group 1); rats intraperitoneally injected with GEN (100 mg/kg/day; Group 2); rats treated with GEN plus distilled water (Group 3); and rats treated with GEN plus NBV (10 mg/kg/day; Group 4). After 15 days, the rats were sacrificed, their kidneys taken, and blood analysis performed. Tubular necrosis and interstitial fibrosis scores were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in other part of kidneys. RESULTS: The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of NBV to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and NBV had significantly lower MDA and NO levels in kidney cortex tissue than that given GEN alone. Despite the presence of mild tubular degeneration, the rats treated with GEN+NBV showed a less severe tubular necrosis, and their glomeruli maintained a better morphology compared to GEN group. CONCLUSION: NBV exerts antioxidant, anti-inflammatory and antifibrotic effects on GEN-induced kidney damage by reducing oxidative stress in rat model (Tab. 3, Fig. 2, Ref. 68).

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.

Lipoprotein-associated phospholipase A2 levels are associated with erectile dysfunction in patients without known coronary artery disease.

Endothelial dysfunction and microvascular damage play a crucial role in the pathogenesis of erectile dysfunction (ED). Lp-PLA2 is a calcium-independent member of the phospholipase A2 family and hydrolyses oxidised phospholipids on low-density lipoprotein (LDL) particles that plays a pivotal role in ox-LDL-induced endothelial dysfunction. The purpose of the current study was to determine the association between Lp-PLA2 levels and ED in patients without known coronary artery disease (CAD). All patients were evaluated for ED and divided into two groups: 88 patients suffering from ED for >1 year were enrolled as an experimental group and 88 patients 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. Levels of Lp-PLA2 were measured in serum by colorimetric assay. The relationship between Lp-PLA2 levels and ED in patients was evaluated statistically. The mean age of patients with ED group was 59.4 ± 11.32 and 55.8 ± 9.67 in the control group. Plasma Lp-PLA2 levels were significantly higher in ED than in the control group (220.3 ± 66.90 and 174.8 ± 58.83 pg ml(-1) , respectively, P < 0.001). The Lp-PLA2 levels were negatively correlated with score of ED (r = -0.482, P < 0.05). In logistic regression analysis, enhanced plasma Lp-PLA2 levels result in approximately 1.2-fold increase in ED [1.22 (1.25-2.76)]. In this study, serum Lp-PLA2 levels were found to be associated with endothelial dysfunction predictive of ED. Serum Lp-PLA2 level appears to be a specific predictor of ED, and it may be used in early prediction of ED in the male population.

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.

Stress urinary incontinence in premenopausal and postmenopausal women: evaluation of serum estradiol levels and bone mineral density.

AIM: Stress urinary incontinence is the most common form of urinary incontinence, occurring in pure or mixed forms in nearly 80% of women with incontinence. Hypoestrogenism may cause female incontinence and low bone mineral density, together. So, we investigated the relationship between stress urinary incontinence, serum E2 levels and osteoporosis in premenopausal and postmenopausal women. METHODS: From February 2011 to March 2012, 78 postmenopausal and 30 premenopausal women with stress incontinence, and 57 continent postmenopausal and 20 premenopausal women included in the study. All women's ages, body mass indexes, comorbidities, numbers of birth, number of pregnancies, serum estradiol levels and T-scores were evaluated and compared between groups. RESULTS: Bone mineral density was evaluated in groups. Osteoporosis was more in women with stress urinary incontinence (P<0.05). E2 levels were found decrease in the postmenopausal and premenopausal women who have stress urinary incontinence compared to control group. we found that the women who have low estradiol levels, usually T score was ≤ -2.5 and have osteoporosis. CONCLUSION: Osteoporotic women should be evaluated for urinary incontinence and vice versa women with urinary incontinence evaluated for osteoporosis. Further studies are needed to clarify molecular mechanisms of these results.

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.