An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis.

INTRODUCTION: The aim of this experimental study was to investigate the histopathological and biochemical effects of pyrrolidine dithiocarbamate, an antioxidant and inhibitor of NF-kß, on ischemiareperfusion injury in rats. METHODS: A total of 21 male Wistar-Albino rats were randomly distributed into three groups as sham group (Group 1), ischemia-reperfusion (I/R) group (Group 2) and I/R with pyrrolidine dithiocarbamate (PDTC) group (Group 3). Left testicles of rats in Groups 2 and 3 underwent testicular torsion of 720° for four hours and 100 mg/kg of PDTC was administered intraperitoneally prior to detorsion in Group 3. An hour after detorsion process, left orchiectomies were performed and 5 ml of intracardiac blood samples were drawn from rats in all three groups. Histopathological examination of testis tissues performed and measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) levels in blood samples were taken. RESULTS: Elevated levels of MDA and decreased SOD activity, together with decreased Johnson tubular biopsy scores consistent with I/R injury were observed in Group 2 (p<0.05). Group 1 and Group 3 were similar in terms of MDA levels, SOD activity, and Johnson scores (p>0.05). CONCLUSIONS: Our results indicated that PDTC may have beneficial effects for alleviation of I/R injury in testicular tissue in rats. Understanding the underlying mechanisms and exploration of its diagnostic and therapeutic potential requires further randomized, controlled trials on a larger scale.

Neutrophil-lymphocyte ratio as a predictor of recurrence and progression in patients with high-grade pT1 bladder cancer.

INTRODUCTION: We investigated the value of the preoperative neutrophil-lymphocyte ratio (NLR) in predicting recurrence and progression of high-grade pT1 non-muscle-invasive tumour in patients with bladder cancer during a 5-year follow-up period. METHODS: We retrospectively reviewed data of 1100 patients with bladder cancer; these patients underwent transurethral resection and were monitored at multiple centres from 2008 to 2013. In total, 166 consecutive and newly diagnosed patients with high-grade pT1 tumours were included in this study. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. RESULTS: Of the 166 patients, 152 were male. The patients were evaluated as two separate groups in terms of recurrence and progression. The mean follow-up period was 24.2 months (interquartile range 13.8-36.6 months). A statistically significant difference was found between recurrence and tumour size (p = 0.001), number of tumours (p < 0.001), NLR (p < 0.001), and smoking (p = 0.007). No statistically significant correlation was found between NLR and progression. According to receiver operating characteristic (ROC) analysis, the optimum cut-off value for the NLR was ≥2.43 (74% sensitivity, 60% specificity, p < 0.001; area under the curve [AUC] 0.687, 95% confidence interval [CI] 0.607-0.767). Multivariate logistic regression analysis determined that the following factors were independent predictors of recurrence in patients with high-grade pT1 non-muscle-invasive bladder cancer: tumour number (OR 5.32, 95% CI 2.10-12.90), NLR of ≥2.43 (OR 2.587; 95% CI 1.156-5.789), and smoking (OR 4.17, 95% CI 1.31-13.21). CONCLUSION: A high preoperative NLR may play an important role in predicting recurrence of superficial transitional cell type high-grade pT1 bladder tumours. Prospective studies are required to validate the role of NLR as a prognostic marker in high-grade pT1 bladder tumours.

Effect of mitomycin, bevacizumab, and 5-Fluorouracil to inhibit urethral fibrosis in a rabbit model.

BACKGROUND AND PURPOSE: Mitomycin C (MMC), bevacizumab, and 5-fluorouracil (5-FU) are frequently used in cancer treatment. Each of these agents also exhibits antiproliferative properties in different tissues. We compared the efficacy of MMC, bevacizumab, and 5-FU may inhibit urethral fibrosis (UF) without statistically significant differences among them. MATERIALS AND METHODS: Forty male rabbits with traumatized urethras were divided into four groups: Group 1 (control), no medical treatment; group 2, MMC applied to the traumatized area; group 3, bevacizumab applied to the traumatized area; and group 4, 5-FU applied to the traumatized area. All animals were euthanized after 28 days to evaluate the presence of chronic inflammation and fibrosis. Tissue samples were subjected to hematoxylin and eosin and Masson trichrome staining to assess the presence of fibrosis, the state of the epithelium, and collagen density. RESULTS: The MMC and control groups showed the most significant difference in outcomes (P<0.001), followed by the bevacizumab (P=0.002) and 5-FU groups (P=0.005). No statistically significant difference was noted when all three treatment groups were compared with one another. Histopathologic examination revealed inflammatory cell infiltration in the connective tissue, irregular collagen bundles, increased fibroblasts, and a moderate degree of fibrosis in the control group. Compared with controls, all treatment groups exhibited mild fibrosis, less collagen bundle irregularity, and lower numbers of fibroblasts. CONCLUSION: MMC, bevacizumab, and 5-FU may inhibit UF. There were no statistically significant differences in the effectiveness among the three agents.

Endothelial nitric oxide synthase gene polymorphisms (promoter -786T/C, exon 894 G/T and intron G10T) in unexplained female infertility.

BACKGROUND/AIMS: Recent investigations in both males and females show that there may also be some genetic risk factors associated with infertility, and endothelial nitric oxide synthase (eNOS) has important functions in implantation. We aimed to investigate the association of three different polymorphisms of eNOS (promoter -786T/C, exon 894 G/T and intron G10T) with unexplained female infertility. MATERIALS AND METHODS: Two groups of patients were included in the study: (1) women with unexplained infertility and (2) healthy, fertile women with normal menstrual cycles. eNOS polymorphisms were studied in genomic DNA of each patient by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Forty-one women with unexplained infertility and 40 fertile women were included. Baseline physical characteristics and hormonal parameters of the two groups were similar. For eNOS exon 894 G/T polymorphism, the GG homozygotes were significantly lower and the heterozygotes GT were significantly higher in the infertile group than in the control group (p < 0.05). eNOS gene polymorphism both for promoter and intron were similar in the two groups (p > 0.05). CONCLUSION: Altered eNOS protein caused by eNOS exon 894 G/T polymorphism might cause implantation failure, which may be a possible cause of unexplained female infertility.

Protective effects of N-acetylcysteine on experimentally undescended testis.

PURPOSE: We evaluated the efficacy of N-acetylcysteine for testicular damage induced by undescended testes in rats. MATERIALS AND METHODS: Flutamide was injected in the abdomen of pregnant rats daily from days 14 to 20 of gestation. Male offspring with cryptorchidism were randomly divided into 2 groups. Healthy male rats without undescended testes comprised the control group (group 1). Group 2 (undescended testes without N-acetylcysteine) received no treatment. Group 3 (undescended testes plus N-acetylcysteine) received intraperitoneal N-acetylcysteine daily. At 70 days after experiment initiation the testes were removed for histopathological and biochemical analysis. RESULTS: Mean malonyl dialdehyde values were lowest in group 1 and highest in group 2. In group 3 malonyl dialdehyde levels were significantly lower than in group 2 (p <0.001). Conversely, mean glutathione peroxidase was highest in group 1 and lowest in group 2. Glutathione peroxidase levels in group 3 were significantly higher than in group 2 (p <0.001). Histopathological differences between groups 1 and 3 in the modified Johnsen score were not significant (p = 0.041). However, the differences between these groups and group 2 were significant (p <0.001). The median apoptotic cell count did not differ between groups 1 and 3 but it was significantly higher in group 2 than in the other groups (p = 0.03 and <0.001, respectively). CONCLUSIONS: N-acetylcysteine may alleviate undescended testis induced damage to testes through its antioxidant effects. The underlying mechanism of these effects merits further investigation. Long-term studies are also needed as well as comparative animal and human studies.