Treatment with melatonin and selenium attenuates docetaxel-induced apoptosis and oxidative injury in kidney and testes of mice.

Docetaxel (DTX) has been used in cancer treatments for several decades, but it results in many adverse apoptotic effects through excessive production of reactive oxygen species (ROS) in some tissue including the kidney and testes. We aimed to investigate potential modulatory roles of melatonin (MEL) and selenium (Se) against DTX-induced apoptosis and oxidative injury in the testes and kidney of mice. Thirty-two mice were divided into four equal groups as control, DTX, DTX + MEL and DTX + Se. DTX group was treated with a single intraperitoneal dose of DTX. After DTX treatment, MEL and Se were administered to the mice in the DTX + MEL and DTX + Se groups for 7 days respectively. Increased lipid peroxidation, ROS, apoptosis, caspase-3 and caspase-9 activities in the kidney and testes of the DTX group were diminished by treatment with MEL and Se. DTX-induced decreases in vitamin E (α- and γ-tocopherol), glutathione peroxidase and reduced glutathione levels in the kidney and testis were increased following MEL and Se treatments. In conclusion, our data show that MEL and Se can act as modulators against DTX-induced apoptosis and oxidative damage in the kidney and testis through up-regulation of glutathione and vitamin E and down-regulation of caspase pathways.

Selenium attenuates docetaxel-induced apoptosis and mitochondrial oxidative stress in kidney cells.

Docetaxel (DTX) is a chemotherapeutic agent, and it is used for the treatment of several cancers including prostate and glioblastoma, but it results in many adverse effects in normal tissues, including kidney. The cytoprotective properties of selenium (Se) against adverse effects of DTX were reported in several normal cells, except kidney cell lines. The purpose of this study was to investigate the effects of Se on DTX-induced nephrotoxicity in normal kidney cell lines. The human embryonic kidney 293 (HEK293) cells were divided into four groups as control, Se (200 nmol/l for 10 h), DTX (10 nmol/l for 48 h), and DTX+Se. Laser confocal microscope fluorescence intensity of apoptosis (annexin V and propidium iodide), mitochondrial membrane depolarization, reactive oxygen species production, and lipid peroxidation levels were increased in the cells by the DTX treatments, although cell number, cell viability, reduced glutathione and glutathione peroxidase values were decreased by the treatments. The fluorescence intensities and values were recovered in the DTX+Se group of the cells by Se treatment. In conclusion, DTX-induced adverse effects were recovered through inhibition of apoptosis and mitochondrial oxidative stress through upregulation of reduced glutathione and glutathione peroxidase in the normal kidney (HEK293) cells. Combination therapy of DTX and Se could be used as an effective strategy for protection of kidney cells against adverse effects of DTX.

ADP-Ribose and oxidative stress activate TRPM8 channel in prostate cancer and kidney cells.

Activation of TRPM8 channel through oxidative stress may induce Ca2+ and pro-apoptotic signals in prostate cancer and kidney cells. The aim of this study was to evaluate activation of TRPM8 can increase apoptosis and oxidative stress in the prostate cancer (Du145M8), TRPM8 knock out (Du 145M8KO), transfected (HEK293TM8) and non-transfected human kidney (HEK293) cells. Intracellular Ca2+ responses to TRPM8 activation were increased in the Du145M8 and HEK293TM8 cells from coming cumene hydrogen peroxide (CHPx), menthol, ADP-Ribose (ADPR), but not in the HEK293 and Du 145M8KO cells. The intracellular Ca2+ responses to both ADPR and CHPx were totally inhibited by the thiol cycle antioxidant glutathione, and TRPM8 blockers (N-(p-amylcinnamoyl)anthranilic acid and capsazepine). Apoptosis, Annexin V, mitochondrial membrane depolarization, intracellular ROS, caspase 3 and 9 values were increased through TRPM8 activation in the Du 145M8 but not in the Du 145M8KO and non-transfected HEK293 cells by CHPx and hydrogen peroxide. In conclusion, apoptotic and oxidant effects on the cells were increased activation of TRPM8 by oxidative stress and ADPR. Activation of TRPM8 through oxidative stress and ADPR in the cells could be used as an effective strategy in the treatment of prostate cancer cells.

Fibroepithelial Polyp of the Ureter: A Rare Cause of Hydronephrosis.

Background: Fibroepithelial polyps of the urothelial system are rare and are considered to be benign tumors. Ultrasonography (USG), contrast-enhanced CT, and contrast-enhanced MRI can be used for detecting fibroepithelial polyps in the urothelial system. These polyps can be treated by performing open exploration and endoscopic or laparoscopic resection. Previous studies have also reported the frequent use of laser treatment for treating fibroepithelial polyps located in the proximal ureter. Case Presentation: A 54-year-old female patient presented to our clinic with right flank pain. Evaluation of the patient by performing USG and CT detected grade-2 hydronephrosis of the right kidney; however, no stone was detected in the urinary system. MRI detected thickening of the wall of the right proximal ureter along with contrast enhancement. These findings suggested the presence of a ureteral polyp. Ureterorenoscopy detected a 7-cm-long ureteral polyp in the proximal ureter, which was resected by performing monopolar cautery. Conclusion: Although fibroepithelial polyps of the urinary tract are rare, they should be considered in the absence of urinary calculi and in the presence of a ureteral obstruction. Furthermore, careful endoscopic resection by performing electrocautery is a safe and useful method for treating ureteral lesions.

The impact of gallic acid on the methotrexate-induced kidney damage in rats.

Prolonged use of an antineoplastic agent methotrexate (MTX), can cause numerous side effects such as nephrotoxicity. The aim of this study was to examine the effects of MTX on kidneys and demonstrate the protective effects of gallic acid (GA). Twenty-four, male, rats distributed into three groups. Each groups consisted eight rats and only saline was administered to the control group. The MTX group received a single dose (20 mg/kg) MTX intraperitoneally. The MTX + GA group received same dose MTX and 100 mg/kg GA orally during the 7 days. Renal functions, oxidative stress markers, histopathological and immunohistochemical changes were evaluated at the end of the experiment. Blood urea nitrogen, creatinine, uric acid levels and tissue oxidative stress markers, total oxidant status and oxidative stress index levels significantly increased and total antioxidant status levels significantly decreased in MTX group compared with the control group. At the histopathological examination hemorrhages, tubular cell necrosis, glomerulosclerosis, inflammatory cell infiltrations and proteinous materials in tubules were noticed in MTX group. Immunohistochemical examination revealed that increased expressions of serum amyloid A (SAA), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE-2) and C-reactive protein (CRP) in tubular epithelial cells of kidneys in this group. There were no immunoreaction with SAA and CRP, only small number of PGE-2 and TNF-α positive tubular epithelial cells were observed in MTX + GA group. In conclusion, all evidence suggested that oxidative stress caused MTX-induced nephrotoxicity and GA prevent the kidney from the nephrotoxicity due to its antioxidant and anti-inflammatory activities.

A Novel Experimental Method for Penile Augmentation Urethroplasty With a Combination of Buccal Mucosa and Amniotic Membrane in a Rabbit Model.

OBJECTIVE: To investigate the results of penile urethral reconstruction using amniotic membrane (AM) and buccal mucosa (BM) grafts, and the simultaneous use of both in a rabbit model. MATERIALS AND METHODS: A total of 28 male rabbits were divided into 4 groups according to grafting style: group 1 (AM), group 2 (BM), group 3 (BM + AM), and group 4 (sham). A standardized urethral defect was created in the 3 initial groups. The sham group underwent only a ventral vertical urethral incision and primary re-suturation. AM grafts were used in group 1, and BM grafts were used in groups 2 and 3. AM grafts were affixed to the BM grafts in group 3 as a covering tissue. Urethrography and endoscopy were performed after the 1st and 2nd months of grafting. The penises were subjected to histopathologic and immunohistochemical assessment for fibroblast growth factor and vascular endothelial growth factor expression. RESULTS: Dehiscence and fistula developed in group 1, whereas 2 fistulas were observed in group 2. No complications developed in group 3. Epithelization at urethras was observed at 4 weeks in all groups, but transformation to urothelial epithelialization occurred at 8 weeks. Marked amelioration and epithelial transformation were observed in group 3. The most prominent fibroblast growth factor expression was observed in group 3. Vascular endothelial growth factor expression was completely negative in group 3 at 8 weeks, indicating complete healing. CONCLUSION: The simultaneous use of AM and BM for ventral onlay penile urethroplasty provides better tissue healing and lower complication rates in comparison to BM alone. Further animal studies or clinical applications are needed.

Do anxiety, stress, or depression have any impact on pain perception during shock wave lithotripsy?

INTRODUCTION: The most important adverse effect during shock wave lithotripsy (SWL) is pain perception. In this study, we evaluated the effect of anxiety, stress, and depression on pain perception during SWL. METHODS: From November 2013 to December 2014, 189 consecutive patients undergoing SWL for kidney stones were evaluated prospectively. Patient characteristics (age, sex, body mass index [BMI], urologic intervention history, the presence of a double-j catheter, and stone-related parameters) were also recorded. Anxiety, stress, and depression states were assessed before the first procedure using the Depression, Anxiety, and Stress Scales (DASS-42), which is a self-report scale. The degree of pain perception was evaluated with a 10-point Visual Analogue Scale (VAS) at the end of the first SWL session. RESULTS: There were no statistically significant differences in terms of VAS scores during SWL between patients with and without anxiety, stress, or depression (p >0.05). Furthermore, no statistically significant relationships were found between VAS scores and patient age, sex, side of the stone, presence of a double-j stent, number of stones, and SWL experience (p >0.05). CONCLUSIONS: According to our findings, anxiety, stress, or depression seemed to have no impact on pain perception during SWL.

Comparison of shockwave frequencies of 30 and 60 shocks per minute for kidney stones: a prospective randomized study.

OBJECTIVE: One of the factors that determines the treatment success of shockwave lithotripsy (SWL) is the frequency of the shockwaves during the procedure. This study compared the efficacy and pain perception of shockwave frequencies at 30 versus 60 shocks/min for kidney stones. MATERIALS AND METHODS: From August 2013 to May 2015, 160 patients with solitary, radiopaque kidney stones were randomized to SWL at 30 shocks/min (group 1) or 60 shocks/min (group 2), with 80 patients in each group. The primary outcome measure was success rate at 3 months after the last SWL session. The secondary outcome measure was pain perception during the procedures. RESULTS: Of the 160 randomized patients, data for a total of 148 patients (74 patients in group 1 and 74 patients in group 2) were analyzed, after the exclusion of the patients lost to follow-up or who required secondary intervention within 3 months. There was no statistically significant difference between the two groups in terms of the success rate at 3 months (68.9% vs 71.6%, p = .719). However, the mean visual analogue scale scores of all the sessions were significantly higher in group 1 than in group 2 (5.83 vs 4.06, p < .05). Stone location, especially the lower calyceal location, was the only significant negative predictor for success according to multivariate logistic regression analysis. CONCLUSIONS: The success rate was similar between these two frequencies. However, pain perception was significantly higher at 30 than at 60 shocks/min.

The effectiveness of extra-scrotal fixation following manual detorsion for testicular torsion: a pilot study in a rabbit model.

INTRODUCTION: To investigate the effectiveness of manual detorsion (MD) and applicability of extra-scrotal fixation for testicular torsion in a rabbit model. MATERIAL AND METHODS: Twelve New Zealand male rabbits were randomized into six groups of two rabbits each. A single-side testicular torsion (TT) model (different degrees, time and sides) was performed in all groups except the Sham group. The groups included: Group 1 (180°; 4 h), Group 2 (720°; 6 h), Group 3 (1080°; 9 h), Group 4 (540°; 1 h), Group 5 (900°; 2 h), and Group 6 (sham-only). Testes were examined by another urologist and radiologist with Color Doppler Ultrasonography (CDU). MD was performed with CDU until blood flow was observed in the affected testis. Extra-scrotal fixation was then conducted in these animals. The testes were then harvested for blinded histopathological examinations. RESULTS: TT was detected in all animals except the control group. The CDU examination detected decreased blood flow only in Group 1. An opposite rate was observed between the spermatic cord diameter and torsion degree. A wrong direction of MD in the first step was observed in two rabbits in Groups 4 and 5. Torsion signs were observed only in Group 3. Rest torsion was observed in Groups 3 and 5 after extra-scrotal fixation. Histopathological examinations showed that testicular damage increased in parallel to torsion duration. CONCLUSIONS: Extra-scrotal fixation after MD along with CDU may be a simple and minimally invasive treatment option in TT therapy. However, this must be verified with further studies.

Is it possible to distinguish testicular torsion from other causes of acute scrotum in patients who underwent scrotal exploration? A multi-center clinical trial.

INTRODUCTION: To assess the clinical presentation of patients who underwent surgical exploration for acute scrotum and to investigate the potentially related factors for differential dignosis. MATERIAL AND METHODS: We retrospectively analyzed the medical records of 97 patients who underwent surgical exploration for acute scrotum between May 2007 and July 2013. The patients were divided into two groups as follows: Group1 included patients with testicular torsion (TT) and Group 2 contained patients with acute scrotal pathologies other than TT, including torsion of the testicular appendage, epididymo-orchitis, trauma and Henoch-Schönlein purpura. The physical examination findings, colour Doppler ultrasound (CDUS) and laboratory findings for the groups were compared. RESULTS: In total, 97 scrotal explorations were carried out for acute scrotum. Group 1 included 72 patients (74.2%) and Group 2 included 25 patients (25.8%). Group 2 was comprised of patients with torsion of the testicular appendage (n = 13), epididymo-orchitis (n = 8), testicular trauma (n = 2) and Henoch-Schönlein purpura (n = 2). In Group 1, 32 cases (44.4%) presented to a hospital less than 6 hours after onset of pain. More than half (64%) of Group 2's cases presented more than 24 hours after pain onset. Fever and pyuria appeared more frequently in Group 2 than in Group 1 and the results reached statistical significance (p = 0.001 and p = 0.044, respectively). Group 1 had more testicular tenderness than Group 2 (p <0.001). Our testicular salvage rate was 59.7%, and 40.3% of patients underwent orchiectomy. CONCLUSIONS: CDUS predicted the diagnosis of TT (sensitivity 98.6%). Furthermore, clinical findings may also play a substantial role in the differential diagnosis of acute scrotum.

Predictive role of hematologic parameters in testicular torsion.

PURPOSE: To evaluate the predictive role of the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet count (PLT) in the diagnosis of testicular torsion (TT) and testicular viability following TT. MATERIALS AND METHODS: We analyzed two study groups in this retrospective study: 75 patients with a diagnosis of TT (group 1) and 56 age-matched healthy subjects (group 2). We performed a complete blood count as a part of the diagnostic procedure, and NLR, PLR, MPV, and PLT values were recorded. We compared the patient and control groups in terms of these parameters. Then, TT patients were divided into two subgroups according to the time elapsed since the onset of symptoms. Subsequently, we evaluated the relationship between the duration of symptoms and these parameters. RESULTS: There were significant differences between groups 1 and 2 in NLR, PLR, and PLT (p<0.001 for all). There was no predictive role of MPV in the diagnosis of TT (p=0.328). We determined significantly high sensitivity and specificity levels for NLR in the prediction of TT diagnosis (84% and 92%, respectively). Furthermore, NLR was significantly related to the duration of symptoms in TT patients (p=0.01). CONCLUSIONS: NLR may be a useful parameter in the diagnosis of TT. Furthermore, NLR may be used as a predictive factor for testicular viability following TT.