Beneficial effects of melatonin compared with allopurinol in experimental testicular torsion

Background/purpose

Several antioxidant agents such as allopurinol have been used to prevent ischemia-reperfusion (I/R) injury-induced tissue damage after experimental testicular torsion so far. The current study was designed to determine the effect of melatonin, which is a potent antioxidant agent, in preventing testicular damage following torsion.

Methods

Sixty prepubertal male Wistar-Albino rats were divided into 5 groups: control (C), torsion (T), torsion plus detorsion (TD), torsion plus allopurinol (200 mg/kg) plus detorsion (A), and torsion plus melatonin (50 mg/kg) plus detorsion (M). Left testes were rotated 720° for 6 hours. The torsed testes were detorsed. Detorsion time was 6 hours. In all groups, left orchiectomies were performed to determine the tissue levels of malondialdehyde (MDA) and histopathologic changes. Blood samples were taken to measure serum creatine phosphokinase (CPK) levels. The results were analyzed statistically.

Results

Serum CPK levels of groups A and M were found to be significantly lower than groups T and TD (P < .05). Tissue MDA levels in group M were statistically different from groups T and TD (P < .05). However, in groups A and T, MDA levels were similar (P > .05). The highest histologic grade was determined in group TD (3.8 ± 0.5). Histologic grade of group M was significantly lower than group TD (P < .001), but there was no histologic difference between testes of groups A and TD (P > .05).

Conclusions

These results have shown that melatonin treatment prevents I/R injury both biochemically and histopathologically, whereas allopurinol treatment prevents it only biochemically in experimental testicular torsion. Melatonin is a potent antioxidant agent more effective than allopurinol in preventing testicular I/R injury.     

Prepubertal testicular torsion: subsequent fertility

Eighteen patients were reviewed 7 to 23 years after prolonged unilateral testicular torsion. They had all undergone surgical untwisting with replacement of the nonviable testis in the scrotum during prepubertal period. Five patients were now married and had fathered one or more children. Thirteen patients were unmarried. There was absence of testis on the affected side in 14 of 18 patients. Four patients had severe testicular atrophy on the affected side (testicular volume less than 1 mL). The contralateral side showed either a normal testicular volume or a compensatory hypertrophy (testicular volume greater than 25 mL). Seminal analysis was done in 13 unmarried men and it was completely normal in 10 patients. Two patients had low sperm density but normal semen volume and motility. One patient had pathologic semen analysis. IgG and IgA specific mixed agglutination reaction (MAR) test did not show evidence of sperm autoantibodies in any patient. Our clinical experience shows that, after prepubertal torsion, the contralateral testis undergoes normal development. Furthermore, torsion in the prepubertal male does not cause autosensitization and diminished fertility in adult life.     

Efficacy of antioxidant treatment in the prevention of testicular atrophy in experimental testicular torsion

Background/Purpose

This study aimed to compare dose schedules of the antioxidant treatment (melatonin and steroid) used as 1 dose and as once a day for 7 days in terms of salvage of the testes in the late period.

Methods

Sixty prepubertal rats were divided into 6 groups each containing 10 rats: sham (S), torsion-detorsion (TD), 1-dose melatonin (M¹), 1-dose steroid (ST¹), 7-dose melatonin (M⁷), and 7-dose steroid (ST⁷) groups. The left testes were rotated 720° for 6 hours and detorsed for 6 hours thereafter. In the treatment groups, 17 mg/kg melatonin and 1 mg/kg steroid were injected 15 minutes before detorsion. Left orchiectomies were performed to determine testicular weights and Johnsen scores 3 months later.

Results

Testicular weights and Johnsen scores in the M¹, ST¹, and TD groups were significantly lower compared with those in the S group, and atrophy developed in these groups, whereas they were higher in the M⁷ and ST⁷ groups compared with the TD group. Testicular atrophy did not develop in the M⁷ or ST⁷ groups.

Conclusions

Our results suggested that antioxidant agents used once a day for 7 days prevent testicular atrophy and are effective in terms of salvage of the testes.     

睾丸扭转的研究进展

睾丸扭转是泌尿外科最常见的阴囊急症之一,常需要急诊手术以争取保留患侧睾丸。有不少学者认为扭转复位后的睾丸仍存在缺血再灌注损伤并且会对患者性激素水平、生育能力等造成威胁。本文通过综述睾丸扭转的研究进展,以期提高临床医生对睾丸扭转的认识。     

The effect of unilateral testicular torsion on the contralateral testicle in prepubertal Chinese hamsters

Recent studies of experimental testicular torsion in rats, rabbits, and guinea pigs have demonstrated conflicting evidence regarding contralateral testicular damage. Those studies in which cellular damage has been found are postulated to result from an immunological mechanism whereby the blood-testis barrier is disrupted with subsequent autoantibody formation. In this study, the histologic and immunologic effects of testicular torsion on the contralateral testicle were investigated in prepubertal Chinese hamsters. Four study groups were established; (1) Left orchiectomy only, (2) sham surgery (scrotal incision), (3) 720 degrees left testicular torsion with left orchiectomy 24 hours later, (4) 720 degrees torsion of left testicle with detorsion after 24 hours. The initial procedure was performed at 1 month of age with subsequent biopsies of the contralateral testicle at 1 week, 1 month, and 6 months after the initial procedure. Testicular tissue was examined for immunofluorescent activity using fluorescent labeled goat anti-hamster IgG. Positive controls were established by rabbit immunization (rabbit anti-hamster immunoglobulin) which was subsequently combined with fluorescent labeled goat antirabbit IgG. There was no appreciable difference in immunologic activity between control and experimental animals. Representative sections were examined histologically and no tubular damage was demonstrated and active spermatogenesis was noted at 6 months in all groups. We believe that our results support the premise that testicular torsion in the prepubertal period has no effect on the contralateral testicle.     

The effects of human chorionic gonadotropin treatment on the contralateral side in unilateral testicular torsion

BACKGROUND/PURPOSE: Unilateral testicular torsion can cause histologic damage, consisting of aspermatogenesis and tubular atrophy, in the contralateral testis human chorionic gonadotropin (HCG) treatment is widely used in undescended testis, and has been shown to improve histomorphometric alterations beside the testicular descent. However, the role of HCG in testicular torsion has not been investigated before. Therefore, this experimental study was conducted to evaluate the effects of HCG treatment on contralateral testicular histology and function in unilateral testicular torsion. METHODS: Forty adult male Wistar rats were randomized into 4 groups: SHAM, SHAM+HCG, TORSION, and TORSION+HCG. Torsion was created by twisting the righ testis 720 degrees and maintained by fixing it to the scrotum. HCG treatment started 24 hours after the torsion at a dose of 100 IU/kg, twice weekly for three weeks. Left orchiectomy was performed one month after the torsion and removed testes were immersed in Bouin's fixative for histopathological evaluation. Mean seminiferous tubule diameter (MSTD) was measured and Johnsen's score was calculated. Blood samples were taken for assaying serum testosteron level. RESULTS: Unilateral testicular torsion resulted in a significant decrease in spermatogenesis and MSTD on the contralateral side. Serum testosteron level was also reduced. HCG treatment improved these parameters in the contralateral 'untwisted' testis beside the serum testosteron. CONCLUSIONS: Our data demonstrates that unilateral testicular torsion adversely effects its counterpart. HCG treatment improves contralateral histomorphometric alterations and serum testosteron in unilateral torsion.     

Perinatal testicular torsion: a unique strategy

Background/Purpose

Perinatal testicular torsion (PTT) is defined as testicular torsion occurring prenatally or within the first 30 days of life. The aim of this study was to evaluate the data obtained from patients with PTT and propose principles of management based on clinical, surgical, and histologic findings.

Methods

A retrospective analysis of 27 boys seen between 1990 and 2005 with surgically documented PTT was conducted. Patients were divided into 2 groups: A, prenatal testicular torsion; B, postnatal testicular torsion. The presence of acute scrotal inflammatory signs defined the urgency to operate.

Results

There were 4 clinical pictures in group A: A1, patients with a nubbin testis (n = 3); A2, patients with a small and hard testis (n = 12); A3, patients with a normal-sized and hard testis (n = 8); and A4, patients with an acute scrotum (n = 2). Group B (n = 2) presented no sign after birth and later developed an acute scrotum. Surgical exploration and histologic examination showed clear signs of a long-standing testicular torsion in groups A1, A2, and A3 or a recent-onset testicular torsion in groups A4 and B. Only one testis could be salvaged (group B).

Conclusions

Clinical signs correlated very well with surgical and histologic findings and can define the need and the urgency to operate. Although testicular salvage rate is very low, the affected side always should be explored to confirm the diagnosis and to fix or remove the affected testicle. The contralateral scrotum also should be explored because of the risk of asynchronous contralateral testicular torsion.     

睾丸扭转(附18例报告)

目的　总结睾丸扭转的诊治经验。　方法　回顾性分析 18例睾丸扭转患者的临床资料。 18例平均年龄 2 3岁 ,<2 5岁者占 83% ,左侧占 83%。发病至确诊时间 5h～ 4 0d ,10h以上者占 89%。　结果　早期误诊 15例。 4例隐睾扭转者行睾丸切除术 ;14例阴囊内睾丸扭转者中 ,11例 (79% )因睾丸坏死予以切除 ,3例手术复位者随访 6个月～ 3年 ,睾丸萎缩 1例。　结论　隐睾扭转应与腹股沟嵌顿疝和急腹症鉴别 ,阴囊内睾丸扭转应与睾丸炎及附睾炎鉴别。早期手术探查对提高睾丸存活率有重要意义     

精索扭转的诊断与治疗(附21例报告)

目的：总结精索扭转的诊治经验。方法：回顾性分析21例精索扭转的临床诊治资料。结果：1例手法复位成功，5例行睾丸复位固定术，15例行坏死睾丸切除术。结论：彩色多普勒超声成像是诊断精索扭转的可靠方法，早期积极手术探查是提高睾丸成活率的关键。     

睾丸扭转和精索扭转的诊断与治疗(附68例报告)

目的:探讨睾丸和精索扭转的诊断与治疗方法,提高睾丸和精索扭转的治疗水平。方法:对68例睾丸和精索扭转的临床资料进行总结,68例平均年龄21岁,<20岁者占84%,左侧55例占80.8%.发病至确诊时间6h～30天,12h以上者占90.2%。结果:53例术前彩色多普勒血流动态显象(CDFI)应作为诊断疾病的常见与首选检查方法。诊断并经手术证实,符合率100%,经手术探查;41例行手术复位、固定,睾丸获救。27例行患侧睾丸切除术,所有病例均行对侧探察,固定。结论:阴囊X核素显象,B超对睾丸精索扭转早期诊断有帮助。早期诊断,及时治疗是提高疗效的关键。彩色多普勒血流动态显象应作为诊断该疾病的常见及首选检查方法,对睾丸精索一旦确诊或疑有精索扭转的患者应及早行紧急复位,以期挽救睾丸,同时行睾丸固定术也十分必要。对于确诊毫无保留价值的睾丸需行切除术。     

Flow cytometric DNA analysis demonstrates contralateral testicular deterioration in experimental unilateral testicular torsion of prepubertal rats

Summary. It has been postulated that unilateral testicular torsion causes damage to the contralateral testis and reduces fertility. However, in animal studies such an effect has not been fully proven by histopathologic examination or other conventional assays of spermatogenesis. We investigated the effect of unilateral testicular torsion on contralateral spermatogenesis in prepubertal rats using quantitative flow cytometric DNA analysis. Male rats were divided into three groups which underwent sham-operation, simple hemiorchiectomy or unilateral testicular torsion. Five weeks after these operations, fertility and spermatogenesis by flow cytometry were evaluated. No significant differences were observed in body weight, contralateral testicular weight or serum testosterone concentration among the three experimental groups. In the torsion group, mean seminiferous tubular diameter, number of foetuses, fertility rate and percentage of haploid cells were all significantly decreased compared to the other two groups. These results suggest that unilateral testicular torsion causes damage to the contralateral testis and consequently can reduce the future fertility of prepubertal rats.     

睾丸扭转诊治体会(附39例报告)

目的 提高睾丸扭转的诊治水平。方法 对39例睾丸扭转患者的临床资料进行总结。39例均有睾丸绞痛症状，Prehn征阳性20例。8例行阴囊核素显像检查，均有放射性分布缺损。B超显示睾丸、附睾在阴囊内位置改变，睾丸内血流减少或消失。结果 5例12h以内手术者，睾丸均存活；5例12～24h手术者，3例睾丸存活；27例超过24h手术者，仅6例睾丸存活。2例未手术。结论 阴囊核素显像、B超对睾丸扭转早期诊断很有帮助。早期诊断、及时治疗是提高疗效的关键。     

Pentoxifylline improves blood flow to both testes in testicular torsion

Objectives: Electromagnetic and radioisotopic studies have shown thatunilateral testicular torsion causes a decrease in contralateral testicularblood flow. Pentoxifylline improves microvascular blood flow in conditionsof vascular insufficiency. An experimental study was designed to evaluatethe effects of pentoxifylline (Ptx) on blood flow to both testes duringunilateral testicular torsion and detorsion.Materials and methods: Thirty-six adult male albino Wistar rats wererandomly divided into six groups where each consisted of six rats: group1: sham operation, group 2: sham operation with Ptx, group 3: torsion,group 4: torsion with Ptx, group 5: detorsion, group 6: detorsion with Ptx.After intraperitoneal administration of Ptx at a dose of 50 mg/kg 15minutes before torsion; right testes of the rats underwent 30 minutes oftorsion and 30 minutes of detorsion. Blood flows of both testes weremeasured during torsion and detorsion simultaneously by using ¹³³Xeclearance technique.Results: Unilateral testicular torsion caused decrease in bilateraltesticular blood flow. Pentoxifylline had no effect on testicular blood flowduring torsion. Detorsion caused a partially increase in blood flow toipsilateral (detorted) testis, but had no effect on contralateral (nontorted)testicular blood flow. Pentoxifylline administration during detorsionsignificantly increased blood flow to both testes.Conclusions: Testicular torsion is a pathological process that causesdecreased blood flow to both testes. Pentoxifylline improves blood flow toboth testes during detorsion in a rat model of testicular torsion. Furtherstudies are needed to evaluate the effects of pentoxifylline on testiculartorsion.     

Assessment of immunological mechanism in infertility of the rat after experimental testicular torsion

Summary A necrotic torted testis left in the scrotum affects the contralateral testis, resulting in depressed fertility. It was suggested that testicular torsion provoked a systemic response of an immunologic nature. In order to prove this theory, 56 rats were operated. Ten had a sham operation, in 17 a testis was torted and excised after 24 h, and in 29 a testis was torted and excised after 24 h, and in 29 a testis was torted but left in situ till the sacrifice. Antisperm-antibodies were not found in any phase of the experiment in the sham group. Using indirect immunofluorescence, antisperm-antibodies were found in the sera of 8/17 rats of the orchiectomy group and in 24/29 of the detorted group. In the direct immunofluorescence study, all the antibodies were localized in the tail of the spermatozoid. The antisperm-antibodies dissappeared after 3 to 6 months.     

The protective effect of erythropoietin infusion on testicular torsion/detorsion: an experimental study

Introduction  The aim of the present study was to evaluate the effects of erythropoietin (EPO) on the histopathology of testes after unilateral testicular torsion and detorsion. Materials and methods  Twenty-five male Sprague–Dawley rats weighing 120 g were used in this study. The rats were randomly divided into three groups, a sham group consisting of five rats and the other two groups consisting of ten rats. In group 1 (sham group), right orchiectomy with no additional intervention was performed. In group 2 (T/D group), torsion was created by rotating the testis 720° in a clockwise direction for 4 h. After a 4-h torsion period, the right testis was detorted and replaced into the scrotum for 4 h. After the torsion, 0.5 cc 0.9% NaCl solution was injected once and three times in a week (total 12 doses). In group 3 (T/D + erythropoietin; EPO group), the same surgical procedure was done as in group 1, but EPO 1,000 IU/kg was injected just before the detorsion and three times in a week. At the end of each procedure, bilateral orchiectomies were performed for the histopathological examinations in all groups. Results  We examined the testes weight, vascularization of the region between the seminiferous tubules, percentage of necrotic seminipherous tubules, and maturation of spermatogenesis in terms of necrosis, sertoli cells, maturation arrest of spermatogenesis, hypospermatogenesis, and normal spermatogenesis of torsioned testis tissues with and without EPO treatment. Extremely significant differences in testicular weight were observed in group 1 compared to groups 2 and 3 (P < 0.001). Conclusion  Administration of EPO significantly influenced the rescue of testicular function by preserving the intact seminiferous tubular morphology, lowering the percentage of necrotic seminipherous tubules, and significantly reducing histological damage (P < 0.05).     

婴幼儿睾丸扭转的早期诊断和治疗方法选择

目的：探讨提高婴幼儿睾丸扭转疗效的方法。方法：对12例睾丸扭转患儿均行阴囊彩超检查,10例提示睾丸扭转。根据病情选择手法复位、睾丸复位 双侧睾丸固定术和切除扭转的睾丸同时固定对侧睾丸。结果：1例行手法复位成功,随访4个月～3年,3例保留睾丸者彩超显示双睾丸血流一致;9例切除睾丸者显示对侧睾丸血流正常。结论：阴囊彩超检查对婴幼儿睾丸扭转的诊断有较大的帮助;婴幼儿睾丸扭转后发生睾丸坏死的比率高,早期诊断、及时治疗是救活睾丸的关键,一旦明确或高度怀疑睾丸扭转,应立即行手术探查。     

Protective effects of immunophilin ligands on testicular torsion/detorsion damage in rats

Objectives  The purpose was to investigate the role of immunophilin ligands in ischemia/reperfusion (I/R)-induced germ cell apoptosis in the rat. Materials and methods  Sprague–Dawley rats were divided into five groups with ten animals in each. In animals undergoing torsion/detorsion, right testes were rotated 720o for 1 h. A baseline group was for basal normal values. The sham-operated group served as a control group. The TD group underwent torsion/detorsion surgery alone; the cyclosporine-A group (TD-CsA) received intravenous cyclosporine injection (5 mg/kg) at the time of detorsion, and the FK-506 group (TD-FK) received intravenous FK-506 (3.5 mg/kg) at the time of detorsion. For measurement of lipid peroxidation and antioxidant enzyme activities, the right testes of five animals in each group were excised after 4-h reperfusion. Germ cell apoptosis indices were determined 24 h following detorsion in the right testes of the remaining five animals in each group. Results  Malondialdehyde (MDA) levels in the TD group were significantly higher compared to control and baseline groups. Moreover, testicular MDA values in TD-CsA and TD-FK groups were significantly lower than in TD. There were also significant decreases in catalase and superxide dismutase activities in the TD group compared to control and baseline groups. These values in TD-CsA and TD-FK groups were significantly higher than in TD. The mean germ cell apoptosis scores were significantly higher in TD animals compared to control and baseline groups; however, CsA and FK-506 treatment significantly reduced the apoptosis compared with the TD group. Conclusion  We have shown that administration of immunophilin ligands in testicular torsion decreases ischemia/reperfusion (I/R) cellular damage. The results of biochemical studies suggest that reduction of oxidative stress along with attenuated neutrophil accumulation by immunophilin ligands may have a major role in their cytoprotective effects.     

Right paratesticular abscess mimicking neonatal testicular torsion and caused by Proteus mirabilis

The clinical presentation of neonatal paratesticular abscess may closely resemble that of, neonatal testicular torsion and the use of scrotal ultrasonography to differentiate the two has low, sensitivity. We propose early operative treatment of suspected neonatal testicular torsion to salvage, the testicle in cases of paratesticular abscesses. This is a report of the successful transinguinal, drainage of a right neonatal paratesticular abscess preoperatively diagnosed as testicular torsion and, caused by Proteus mirabilis. The testicle was salvaged.     

Protective role of erythropoietin during testicular torsion of the rats

Testicular torsion is an important clinical urgency. Similar mechanisms occurred after detorsion of the affected testis as in the ischemia reperfusion (I/R) damage. This study was designed to investigate the effects of erythropoietin (EPO) treatment after unilateral testicular torsion. Fifty male Sprague-Dawley rats were divided into five groups. Group 1 underwent a sham operation of the right testis under general anesthesia. Group 2 was same as sham, and EPO (3,000 IU/kg) infused i.p., group 3 underwent a similar operation but the right testis was rotated 720° clockwise for 1 h, maintained by fixing the testis to the scrotum, and saline infused during the procedure. Group 4 underwent similar torsion but EPO was infused half an hour before the detorsion procedure, and in group 5, EPO was infused after detorsion procedure. Four hours after detorsion, ipsilateral and contralateral testes were taken out for evaluation. Treatment with EPO improved testicular structures in the ipsilateral testis but improvement was less in the contralateral testis histologically, but EPO treatment decreased germ cell apoptosis in both testes following testicular IR. TNF-α, IL-1β, IL-6 and nitrite levels decreased after EPO treatment especially in the ipsilateral testis. We conclude that testicular I/R causes an increase in germ cell apoptosis both in the ipsilateral and contralateral testes. Eryhropoietin has antiapoptotic and anti-inflammatory effects following testicular torsion.