Ersagun Karagüzel

Mechanisms of testicular torsion and potential protective agents.

Testicular torsion is a urological emergency most commonly seen in adolescence, involving a decrease in blood flow in the testis resulting from torsion of the spermatic cord that can result in gonad injury or even loss if not treated in time. Testicular ischaemia–reperfusion injury represents the principle pathophysiology of testicular torsion, with ischaemia caused by twisting of the spermatic cord, and reperfusion on its subsequent release. Many cellular and molecular mechanisms are involved in ischaemia-reperfusion injury following testicular torsion. Studies have investigated the use of pharmacological agents as supportive therapy to surgical repair in order to prevent the adverse effects of testicular torsion. Numerous substances have been proposed as important in the prevention of post-ischaemia–reperfusion testicular injury. A range of chemicals and drugs has been successfully tested in animal models for the purpose of mitigating the dangerous effects of ischaemia-reperfusion in testis torsion.

The short term effects of resveratrol on ischemia–reperfusion injury in rat testis

PURPOSE The purpose of this study was to identify changes taking place in the rat testis at the 24th hour of reperfusion following testicular torsion and to evaluate the effects of resveratrol (RSV), a powerful antioxidant, in preventing these changes using novel biochemical parameters and histopathology. METHODS Eighteen adult male rats were divided into three groups: Sham-operated (S), torsion/detorsion (T/D), and T/D+RSV groups. In the T/D group, testicular ischemia was achieved by rotating the left testis 720° clockwise for 4h. In the T/D+RSV group, 20mg/kg RSV was administered intraperitoneally 30 min before detorsion. All rats were sacrificed 24h after detorsion. Serum and tissue malondialdehyde (MDA) concentrations, ischemia modified albumin (IMA), total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and histopathological damage score were analyzed. RESULTS Serum MDA, IMA, TOS, and OSI levels rose significantly in the T/D group. Serum MDA and IMA values were lower in the T/D+RES groups, but not significantly. OSI and TOS values were lower in the T/D+RES group, and the difference was significant. TAS values decreased significantly in the T/D group and rose in the T/D+RSV group, but not significantly. Ipsilateral tissue MDA values were significantly elevated in the T/D group and decreased in the T/D+RSV group, but not significantly. Apoptosis and histopathological damage increased significantly in the T/D group and decreased significantly in the T/D+RSV group. In the contralateral testis, apoptosis increased significantly in the T/D group. It decreased significantly in the T/D+RSV group. CONCLUSIONS Our findings show that RSV had a protective effect against oxidative damage induced with a testicular T/D model, especially at the antiapoptotic and histopathological level. OSI may be a good guide to the clinical status of testicular T/D.

A comparison of the effects of N-acetylcysteine and ethyl pyruvate on experimental testicular ischemia-reperfusion injury

OBJECTIVE To compare the effects of N-acetylcysteine (NAC) and ethyl pyruvate (EP) on experimental testicular ischemia-reperfusion (I/R) injury. DESIGN Randomized, controlled, experimental study. SETTING University hospital. ANIMAL(S) Twenty-four mature male Wistar rats. INTERVENTION(S) Rats were divided into four groups: control group, torsion-detorsion (T/D) group, EP group, and NAC group. In the pretreatment of the NAC and EP groups, 20 mg/kg NAC and 50 mg/kg EP were given intraperitoneally (IP) 30 minutes before detorsion. MAIN OUTCOME MEASURE(S) Serum ischemia-modified albumin (IMA), tissue and serum malondialdehyde, and myeloperoxidase activity levels and histopathological damage scores were then compared. RESULT(S) Ethyl pyruvate and N-acetylcysteine exhibited a protective effect against I/R injury. Of the biochemical parameters evaluated as a result of testicular I/R, only IMA levels were significantly elevated. There was a strong and significant correlation between serum IMA levels and histopathological injury scores, and the increase in serum IMA level exhibited a strong parallel with the increase in histopathological injury. In the EP group, although the histopathological injury score was similar to that of the control group, serum IMA levels were significantly elevated. CONCLUSION(S) Both NAC and EP, the effects of which on I/R injury are evaluated in the present study, reduce such injury in testicular torsion-detorsion. Comparing their effects on IMA levels, NAC may be regarded as a relatively more effective treatment than EP.

Comparison of the protective effect of dipyridamole and acetylsalicylic acid on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury☆

PURPOSE Ischemia reperfusion injury arising from testicular torsion results in a loss of spermatogenesis and a significant increase in germ cell apoptosis. We investigated the effects of dipyridamole and acetylsalicylic acid (ASA), 2 well-known platelet inhibitors, on testicular ischemia reperfusion injury. METHODS Thirty adult male Sprague-Dawley rats were randomly divided into 5 groups (n = 6 for each group): control, sham-operated, torsion/detorsion (T/D), T/D + dipyridamole, and T/D + ASA. Testicular ischemia was achieved by rotating the left testis 720° clockwise for 2 hours. Thirty minutes before torsion, 10 mg/kg dipyridamole was injected transperitoneally in the T/D + dipyridamole group, and 100 mg/kg ASA was injected transperitoneally in the T/D + ASA group. Sixty days after the initial surgical procedure, ipsilateral orchiectomies were performed for histopathologic examination to determine Johnsens mean testicular biopsy score (MTBS), mean seminiferous tubular diameter (MSTD), and apoptotic index (AI) in all groups. RESULTS Unilateral testicular torsion-detorsion led to a significant decrease in Johnsens MTBS and MSTD values in the ipsilateral testis and a significant increase in AI values of the T/D group. There were no significant differences between the T/D + dipyridamole and control groups in terms of MSTD and MTBS values. Although an amount of improvement exits in T/D + ASA group, there were significant differences between the T/D + ASA and control group MSTD and MTBS values. There was no significant difference between the T/D + dipyridamole and control groups in terms of AI values (P > .05), but the differences between the T/D + ASA and control groups were significant despite a slight decline in AI values of the T/D + ASA group. CONCLUSIONS Our findings show that the use of dipyridamole before testicular reperfusion has a potentially protective effect against long-term injury in testicular ischemia reperfusion injury.

The Diagnostic Value of Plasma SCUBE1, a Novel Biomarker of Platelet Activation, in Testicular Torsion: A Randomized, Controlled, Experimental Study.

OBJECTIVE To investigate the potential diagnostic value of plasma signal peptide, CUB (complement proteins C1r/C1s, Uegf, Bmp1) domain, epidermal growth factor (EGF)-like 1 (SCUBE1) protein in experimentally induced testicular torsion (TT). MATERIALS AND METHODS In this randomized, controlled, experimental study, 24 mature male Wistar rats were divided into four groups: 2- and 4-hour control (groups I and III, respectively), and 2- and 4-hour torsion (groups II and IV, respectively) groups. Torsion was performed by rotating the left testis 720° clockwise and maintained by fixing the testis. Plasma SCUBE1 levels and histopathological damage scores were compared. RESULTS There was significantly greater histopathological damage in the 4-hour torsion group compared with the other groups. SCUBE1 levels in this group were also higher than those in the other groups, and the difference was significant. There were significant correlations between histopathological scores and SCUBE1 levels. CONCLUSION SCUBE1, a novel marker of platelet activation, is elevated in TT. According to our results, platelet activation may play an important pathological role in tissue injury associated with testicular ischemia. Plasma SCUBE1 measurement may have diagnostic, therapeutic, or prognostic value in TT.

Effect of valproic acid treatment on penile structure in prepubertal rats.

INTRODUCTION The aim of this study was to determine the histological effects of valproic acid (VPA) on the penis in prepubertal rats. METHODS Twelve male Wistar rats (21-24 days old) were divided equally into 2 experimental groups, and given tap water (control group) or 300mg/kg/day VPA via gavage for 30 days. After the penes had been harvested, the antiangiogenic and antifibrogenic properties of VPA were evaluated immunohistochemically using vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), transforming growth factor-beta 1 (TGF-β1) and Massons trichrome staining. Apoptosis was determined by caspase-3 and caspase-9 immunoreactions. Results were expressed as histochemical score (HSCORE), a semi-quantitative analysis for the intensity of immunohistochemical reactivity. RESULTS Immunohistochemical HSCORE decreased for VEGF and TGF-β1 staining and increased for iNOS staining in rats treated with VPA compared with the control group. Intensities of caspase-3 and caspase-9 labeling were also significantly increased by administration of VPA. Massons trichrome staining exhibited a fairly diminished level of collagen in the corpus cavernosum of rats treated with VPA. CONCLUSION In the light of these results, the administration of VPA from prepuberty to adulthood led to increased apoptosis and deterioration of the smooth muscle/collagen ratio in rats corpus cavernosum.

Postcircumcisional Ischemia of the Glans Penis Treated with Pentoxifylline

Ischemia of the glans penis is a rare postcircumcision complication. We describe a four-year-old boy developing ischemia of the glans penis 48 h after circumcision. The ischemia completely resolved following treatment with iv pentoxifylline (PTX) for six days, and the patient was discharged without any problems. PTX treatment should be kept in mind as an alternative treatment modality in ischemia of the glans penis which is a serious potential post-circumcision complication.

Effect of Tadalafil on Renal Resistivity and Pulsatility Index in Partial Ureteral Obstruction

Introduction: To investigate the effect of tadalafil on Resistivity Index (RI) and Pulsatility Index (PI) in partial unilateral ureteral obstruction (PUUO). Methods: Twelve New Zealand rabbits were assigned into two groups. Baseline renal Doppler ultrasonography (USG) was performed in all rabbits. The rabbits in group 1 received tadalafil for a month (10 mg/72 h) and group 2 was defined as sham. After 1 month, in both groups left PUUO was created. Renal Doppler USG was performed to measure RI and PI parameters of both kidneys on the 4th hour and 1st and 3rd days postoperatively. Results: Baseline renal Doppler USG revealed that there was no difference between two kidneys in both groups. The differences in mean RI and PI values of the kidneys between the sham and tadalafil groups were not statistically significant. Compared with the preoperative values, postoperative RI and PI values for the left kidneys were significantly increased in the period from 4 h to 3 days postoperatively in the sham group (p < 0.05). However, mean RI and PI values were not increased in the tadalafil group when compared with the sham group and this difference between the two groups was significant (p < 0.05). Conclusions: Tadalafil has a lowering affect on RI and PI in experimentally created PUUO.

Investigation of tyrphostin AG 556 for testicular torsion-induced ischemia reperfusion injury in rat

OBJECTIVE To investigate the effects of tyrphostin AG 556, a tyrosine kinase inhibitor (TKI) in an experimental model of testicular ischemia-reperfusion (I/R) injury. MATERIAL AND METHODS Twenty-four adult male rats were randomly divided into four groups (n = 6): sham, torsion/detorsion (T/D), T/D + dimethylsulfoxide (DMSO) (vehicle group), and T/D + DMSO + tyrphostin AG 556. Testicular torsion was achieved by rotating the left testis 720° clockwise for 4 h. Thirty minutes before detorsion, 3 mg/kg tyrphostin AG 556 was injected transperitoneally in the AG 556 group and DMSO was injected transperitoneally in the DMSO group. After 2 h of reperfusion arterial blood samples were collected for biochemical analysis for malondialdehyde (MDA), ischemia modified albumin (IMA), SCUBE1 (signal peptide-CUB [complement C1r/C1s, Uegf, and Bmp1] and EGF [epidermal growth factor] like domain-containing protein 1), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) parameters, and ipsilateral orchiectomies were performed for histopathological examination based on the semi-quantitative Johnsens mean testicular biopsy score (MTBS) in all groups. RESULTS Tyrphostin AG 556 exhibited a protective effect against I/R injury in testicular torsion. Of the biochemical parameters evaluated as a result of testicular I/R, IMA, MDA, and TOS levels were significantly elevated. There was no significant difference in terms of these biochemical parameters between the sham and AG 556 groups. Significant histopathological injury was determined by comparing the T/D and sham groups. According to histopathological injury scores, significant differences were determined between T/D and AG 556 groups and between AG 556 and sham groups. AG 556 had a superior improving effect on Johnsens scores than DMSO. CONCLUSIONS Our results suggest that the use of tyrphostin AG 556 prior to testicular reperfusion has a protective effect against testicular I/R injury.

Knotted ureteral stent: a rare complication of ureteral stent usage

The use of ureteral stents has become a routine urological practice. There are many different complications with ureteral stent use. One rare complication is knotting, which can be a very difficult condition to treat. We report a case in which a complete knot was found in the proximal part of an indwelling ureteral stent with a proximal ureteral stone.