Protective effect of MOTILIPERM in varicocele-induced oxidative injury in rat testis by activating phosphorylated inositol requiring kinase 1α (p-IRE1α) and phosphorylated c-Jun N-terminal kinase (p-JNK) pathways.

CONTEXT: MOTILIPERM was prepared as a mixture of extracts of three medicinal herbs [roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliaceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae)]. OBJECTIVE: To investigate the role of reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress in a rat model of varicocele and the therapeutic efficacy of MOTILIPERM in this model. MATERIALS AND METHODS: Sixty male rats were divided into five experimental groups: a normal control group (CTR + vehicle), a control group administered MOTILIPERM 200 mg/kg (CTR + M 200), a varicocele-induced control group (VC + vehicle) and two varicocele-induced groups administered MOTILIPERM 100 (VC + M 100) or 200 (VC + M 200) mg/kg for 4 weeks. Testis weights were recorded and serums were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathology, analyses of ER response protein expression levels and oxidative stress were assessed by measuring ROS, reactive nitrogen species (RNS), malondialdehyde (MDA) level and ratios of total glutathione (GSH)/oxidized GSH (GSSG). RESULTS: MOTILIPERM treatment of varicocele-induced groups significantly increased left testis weight, testosterone level, sperm motility, count and spermatogenic cell density. ER-response protein expression levels were dose-dependently decreased in VC + M 200 group compared with VC + vehicle group. MOTILIPERM treatment also decreased MDA and ROS/RNS level but increased GSH/GSSG ratio. DISCUSSION AND CONCLUSIONS: This study suggests that ROS-related ER stress may play a major role in varicocele-induced infertility and MOTILIPERM, a novel compound targeting ROS-based ER stress, may be therapeutically useful in treatment of varicocele, or as a supplement for the treatment of infertility.

La escleroterapia con espuma es un método eficaz para el tratamiento de la insuficiencia venosa / Foam sclerotherapy is an effective method for the treatment of venous insufficiency

«La escleroterapia puede mucho más de lo que en general imaginamos. Teóricamente lo puede todo (Mollard 1994)». En esta reflexión, este cirujano vascular, intuye la potencialidad de los esclerosantes en la nueva forma farmacéutica acabada de nacer. La escleroterapia, procedimiento técnicamente ciego, no evolucionaba, permanecía durante décadas como complemento a la cirugía. No podía progresar porque estaba presa de limitaciones inherentes a la forma líquida de los productos utilizados que impiden hacer suyos los requerimientos básicos de la escleroterapia: a) Conocimiento de la concentración intravascular del esclerosante. b) Homogénea, extensa y manejable distribución sobre las paredes venosas. c) Control del tiempo de contacto esclerosante-endotelio. La clave de la escleroterapia se encierra en el control de la acción de los fármacos esclerosantes y este control se consigue con la forma farmacéutica de espuma inyectable; con ella la escleroterapia rápidamente evoluciona hasta alcanzar una nueva era

'Sclerotherapy can be much more than we generally imagine. Theoretically, it can be everything. (Mollard 1994)'. In this reflection, a vascular surgeon sensed the potentiality of sclerosing agents in the recently created new pharmaceutical form. Sclerotherapy, technically a blind procedure, did not evolve; it remained as a complement to surgery for years. It was unable to progress because it was a prisoner of the imitations adherent to the liquid form of the products used, which that impeded compliance with the basic requirements of sclerotherapy: a) Knowledge of the intravascular concentration of the sclerosing agent. b) Homogeneous, extensive, and manageable distribution of the venous walls. c) Temperature control of the sclerosing agent-endothelium contact. The key to sclerotherapy involves controlling the action of the sclerosing drugs, and this control is achieved in the pharmaceutical form of an injectable foam, and with this, sclerotherapy rapidly advanced until reaching this new era. Nowadays, different therapies are used in the treatment of varicose veins, including radiofrequency and laser ablation, stripping, surgery, echanical-chemical systems, steam, and glue, with very different outcomes. Sclerotherapy is a minimally invasive technique used for more than a hundred years, and useful for treating tiny little veins, until recently, in 1993, a pharmaceutical grade foam was developed that succeeded in treating large varicose veins, and is imitated by many others. The physical-chemical features of these foams vary considerably among themselves, depending on the production technique, concentration of sclerosing agent, types of gases used, gas/liquid proportion, type of gas/ size of bubble ratio, as well as varying in their safety and therapeutic use. The optimal liquid/gas proportion is obtained when there is sufficient liquid for the bubbles to be spherical and with the smallest diameter possible, but without introducing excess sclerosing liquid, which is described as kugelschaum (wet foam) or alternatively, it forms polyederschaum (dry foam). A series of experimental and theoretical studies have been conducted with the purpose of investigating the mechanical and rheological properties of the foams. However, to study its dynamic behaviour is a challenging theoretical problem, due to the complex interaction between the physical phenomena that occur in different longitudinal scales (that is to say, from the molecular to the macroscopic). And, in this interesting time of the evolution of the injection of drugs deposited over bubbles, is where we currently are

The effects of Lichtenstein tension-free mesh hernia repair on testicular arterial perfusion and sexual functions.

INTRODUCTION AND AIM: Lichtenstein tension-free mesh hernia repair has been gold standard for treatment of inguinal hernia. Studies have demonstrated that the complication rate is low. However, because the structures in spermatic cord pass through a narrow space, there has been concern about injury to testicular artery, vein, and vas deferens. The aim of this study was to evaluate the effects of Lichtenstein tension-free mesh hernia repair on testicular arterial perfusion and sexual functions in early phase after the operation. METHODS: Forty male patients underwent tension-free mesh hernia repair. All of them underwent Lichtenstein tension-free mesh hernia repair under spinal anesthesia. Patients were evaluated for local wound complications such as seroma, hematoma, and infection on days 1 and 7. To evaluate the effects of surgery on sexual activity, pain was graded on a scale of 1 to 10 by visual analog scale (VAS). International Index of Erectile Dysfunction (IIEF-5) questionnaire was used in our study to evaluate sexual dysfunction. Testicular arterial flow was reevaluated by Doppler ultrasound. Patients were questioned about erectile dysfunction and sexual satisfaction as well as pain limiting their daily activities and sexual function. RESULTS: Mean operation time was 38 ± 5 (23-122) minutes. Preoperative/postoperative mean flow velocity for operation side (ipsilateral) was 5.13 ± 2.7 ml/min and 6.3 ± 2.3 ml/min respectively and the difference was statistically significant (p = 0.008). VAS scores in preoperative and postoperative periods were compared and had mean values of 0.6 ± 1.4 and 0.8 ± 1.7 respectively and the difference was not statistically significant. CONCLUSION: Lichtenstein tension-free mesh hernia repair does not have any negative effects on testicular perfusion and sexual function; it can be performed safely for treatment of inguinal hernia.

Varicocele en adolescentes: revision y guias para la practica diaria / Varicocele in adolescents: a review and guideline for the daily practice

OBJETIVO: El varicocele en el adolescente es uno de los temas mas difíciles en Urología pediátrica. ¿Cual debería considerarse una buena indicación de tratamiento y a que edad? . ¿Mejora la fertilidad con el tratamiento? .Podemos esperar? .¿Cual es el mejor tratamiento quirúrgico y mínimamente invasivo? Para contestar a estas preguntas ofrecemos una guía clínica para la practica diaria. METODOS: Realizamos una búsqueda en Pub Med de la literatura en habla inglesa de los últimos diez años utilizando las siguientes palabras clave "varicocele", "diagnostico", "tratamiento", "fertilidad" y "adolescente". Después resumimos y comparamos los resultados de estos estudios. CONCLUSIONES: Los adolescentes con varicocele necesitan un seguimiento regular incluyendo la medición del testículo por exploración física y ecografía. En aquellos en los que haya una discrepancia del tamaño de mas del 20% entre el testículo izquierdo y el derecho durante un periodo de 12 meses y los que tengan dolor necesitan varicocelectomía independientemente de la edad del paciente, el estadio de Tanner o el tamaño del varicocele. El pico de flujo retrogrado (PFR) parece ser una buena herramienta no invasiva en el seguimiento y puede ser de ayuda para seleccionar pacientes para cirugía. Un PFR.38 cm/s en combinación con una asimetría testicular mayor o igual al 20% es un argumento para la cirugía independientemente de la edad, el estadio de Tanner o el tamaño del varicocele. Con un PFR<30 cm/s en combinación con una asimetría testicular <20% debería hacerse seguimiento anual. En caso de empeoramiento del PFR o de la asimetría se debe operar. Los pacientes aptos para manejo conservador deberían hacer seguimiento hasta que sea posible realizar un seminograma. Presentamos un algoritmo para el manejo del adolescente con varicocele. Los mejores resultados del tratamiento del varicocele se obtienen con las técnicas microscópicas subinguinales y las laparoscópicas con preservación de linfáticos como demuestra el metaanálisis realizado en esta revisión (AU)

OBJECTIVES: varicocele in adolescent men is one of the most challenging topics in pediatric urology. What should be considered as a good indication for treatment and at what age? Does treatment improve fertility? Can we wait? What is the best surgical and minimal invasive treatment? To answer these questions we provide a guideline to use in daily practice. METHODS: we performed a search of the English literature of the last ten years through the Pub Med database using the following key words "varicocele", "diagnosis", "treatment", "fertility" and "adolescent". We then summated and compared the results of these studies. CONCLUSION: adolescents with varicocele need regular follow-up including clinical examination and ultrasound measurements of the testis. Those with a persistent discrepancy between left and right testis size of more than 20% over a period of 12 months and those with pain need varicocelectomy independent of patient age, Tanner stage or varicocele size. The peak retrograde flow (PRF) seems to be a good diagnostic non-invasive tool in the follow-up and can be of help to select patients for surgery. PRF.38 cm/s in combination with testicular asymmetry minor=20% is a reason for surgery independent of age, Tanner stage or varicocele size. PRF<30 cm/s in combination with testicular asymmetry <20% should be followed annually. In case of worsening PRF or asymmetry surgery must be performed. Patients suitable for conservative management should be followed until semen analysis is possible. We present a flow-chart to use in the management of adolescent varicocele. The best results of varicocele treatment are obtained with microscopic subinguinal and laparoscopic lymphatic spearing techniques as shown in a meta-analysis performed in this review (AU)

The effect of micronized purified flavonoid fraction on the prevention of testicular pathologies in adolescent rats with experimentally induced varicocele.

PURPOSE: We investigated the effect of micronized purified flavonoid fraction on the prevention of testicular pathologies following varicocele induction. MATERIALS AND METHODS: A total of 66 adolescent (6-week-old) male Wistar rats were included in study. Rats were divided into 7 groups, including group 1--control, group 2--sham operation, group 3--left varicocele induced, group 4--varicocele induced, varicocelectomy done 4 weeks later and micronized purified flavonoid fraction administered for 4 weeks, group 5--varicocele induced and micronized purified flavonoid fraction administered for 8 weeks, group 6--varicocele induced and beginning 4 weeks later micronized purified flavonoid fraction administered for 4 weeks, and group 7--varicocele induced and varicocelectomy done 4 weeks later. Before sacrifice bilateral real-time testicular microvascular perfusion of all rats was measured using the PeriFlux System 5000 PF 5010 LDPM Unit (Perimed, Järfälla, Sweden). All testes were graded according to the Johnsen scoring system. To assess apoptosis caspase-3 levels were measured. RESULTS: Testicular weight in group 3 was markedly decreased and the extent of seminiferous tubular damage was significantly increased compared with the other groups. Bilateral testicular blood flow and the number of apoptotic germ cells were greater in group 3. Significantly higher Johnsen scores and a meaningful decrease in the apoptotic index were detected in groups 4 to 7 compared with group 3. CONCLUSIONS: We observed favorable effects of micronized purified flavonoid fraction on the regression of testicular damage secondary to varicocele.

Andrological aspects of physical exercise and sport medicine.

Appropriate physical activity is one of the bases of healthy lifestyle. In fact, physical exercise and playing sport may be associated with both improvements and injury to both general and reproductive health. A biologically normal testosterone secretion appears fundamental in males to guarantee both a physiological exercise adaptation and safe sport participation. The reproductive system is highly sensitive to the effects of exercise-related stress and the reproductive hormones may both increase and decrease after different acute or chronic exercises. Exercise and sport participation may positively or negatively influence andrological health status depending on the type, intensity and duration of performed physical activity and on individual health status. In addition, prohibited substances administration (e.g. androgenic-anabolic steroids, and so forth) in competitive and non-competitive athletes represents the main cause of iatrogenic andrological diseases. Preventing and treating andrological problems in active healthy and unhealthy individuals is as important as promoting a correct lifestyle. Physicians need to be educated on the relationships between the male reproductive system and sport participation and on the great role of the pre-participation physical examination in the prevention of andrological diseases.

Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats.

In rat experimental varicocele, polydeoxyribonucleotide (PDRN) induces vascular endothelial growth factor (VEGF) production, thereby enhancing testicular function. This may point to a new therapeutic approach in human varicocele.

Inguinal hernias and genital abnormalities in young Jordanian males.

This study was carried out to document the prevalence of inguinal hernia, hypospadias, undescended testis and varicocele in 3057 male applicants to the military wing of Mu'ta University in the south of Jordan. Age range was 17-20 years. A total of 250 men had one the 4 conditions: 93 (3.0%) had inguinal hernia; 15 (0.5%) had undescended testis (26.7% bilateral); 59 (1.9%) had hypospadias; 83 (2.7%) had varicocele (98.79% on the left side). Prevalence of inguinal hernia and undescended testis were comparable with international prevalence rates, while the rate for hypospadias was higher and that for varicocele lower. A birth defects registration system would help in planning preventive and treatment strategies.

[Doppler study in the evaluation of results of varicocele treatment in teenagers]. / Dopplerografiia v otsenke rezul'tatov lecheniia varikotsele u podrostkov.

Results of treatment in 62 patients with varicocele were evaluated with anamnestic, physical and Doplerographic data. Recurrence of varicocele was seen after the Palomo surgery in 4.9% patients. Hydrocele reoccured after surgery in 2 teenagers. Doppler study revealed that 37.5% patients had orthostatic extravasal obstruction of the left renal vein in the aortomesenterial "forceps" (0.15 +/- 0.03 cm, p > 0.05) with a significant decrease in volumetric blood flow velocity by 44 +/- 30.01 ml/min. Postsurgical signs of venous renal hypertension were seen in 2 patients. Doppler ultrasound study more objectively evaluate long-term results of varicocele treatment.

[Choice of surgical method in the treatment of varicocele]. / Vybor metoda operativnogo lecheniia varikotsele.

The data are presented on 788 patients with varicocele and impairment of spermatogenesis. All the patients were divided into two groups. Group 1 consisted of 240 patients not examined with ultrasound dopplerography who had undergone Ivanissevich operation with estimation of spermatogenesis before and 12 months after the operation. Improvement on the spermatograms was observed in 167 of 227 (73%) patients. Group 2 consisted of 548 patients. Hemodynamic alterations were examined in 342 (62.4%). After this examination they were operated by Ivanissevich. Improvement of spertmatogenesis was achieved in 285 (90.4%) patients. Sapheno-testicular intervenous anastomoses were established in 183 patients. 168 (92%) of them improved spermatogenesis. Recurrences were detected in 19 (8%) and 10 (5.4%) patients of groups 1 and 2, respectively. The above treatment policy promoted recovery of sperm fertility in operated patients and makes recurrences less frequent.

[Role of spermatic vein phlebography and scleroembolization in treating varicocele and preventing its recurrence]. / Znachenie flebografii i kombinirovannoi skleroémbolizatsii vnutrennikh semennykh ven dlia lecheniia i preduprezhdeniia retsidivov varikotsele.

The phlebograms and intravascular treatment of varicocele were performed in 406 patients aged from 10 to 60 years. Scleroembolization of the left internal spermatic vein was successfully used in 402 of them. Dilatation and retrograde flow through the right internal spermatic vein were recorded in 101 of 238 patients during transjugular catheterization. This investigation has confirmed high effectiveness of the method of the intravascular combined scleroembolization in treatment of varicocele. Using the transjugular access facilitates not only performing the left side intervention but represents the only efficient means to fulfill the right side phlebography of the spermatic vein and its obliteration. The strategy of using the bilateral intervention for the detection of retrograde contrast of the right internal spermatic vein considerably improves the results of treatment of varicocele and decreases risk of relapses.

Comparison of early deflation rate of detachable latex and silicone balloons and observations on persistent varicocele.

PURPOSE: To determine the frequency of and time until spontaneous deflation of detachable embolization balloons made of different materials and the correlation between persisting or recurrent varicocele and the spontaneous deflation of the balloons. MATERIALS AND METHODS: Forty-five patients with clinically detected left-sided varicocele underwent embolization with 78 silicone and 22 latex balloons. The minimum follow-up time was 3 months and the follow-up consisted of clinical examination, color duplex ultrasonography, and plain radiography of the balloons. Those patients who were suspected of having recurrent varicoceles underwent control venography to assess the internal spermatic vein. RESULTS: All of the latex balloons and 10% of the silicone balloons deflated spontaneously during the follow-up. The average time until deflation was 5.1 months for latex and 9.9 months for silicone balloons. Persistence of varicocele, attributed to perfusion through a previously occluded portion of the internal spermatic vein, occurred in two of 11 (18%) recurrences. Nine of 11 (72%) recurrences were due to bypassing collaterals past the site of detachable balloon placement. CONCLUSIONS: Latex balloons seem to predispose more to persisting/recurrent varicocele than silicone balloons. Early deflation of the balloons explained two (18%) of the 11 persisting or recurrent varicoceles. A combination of a sclerosing agent with balloon embolization of the internal spermatic vein is recommended.

Laparoscopic varicocele operation: a chance to prevent the recurrence.

There are recurrences and postoperative hydrocele of varicocele after any kind of surgical treatment. Laparoscopic clipping and dissection of internal spermatic vessels was performed without any complication in 73 children to treat varicocele in our department between 1995 and 1998. We have used a new method to detect etiological factors at laparoscopic surgery. The well-known Linton and Trendelenburg test was adapted to detect incidental collateral veins in 73 patients. Using these test, collateral veins were detected in 16 boys. The testicular artery identified in most of the cases as a pulsatile vessel. The operating time was 10-25 minutes. Laparoscopic varicocelectomy is a safe, effective treatment causing minimal discomfort and allowing patients an early to return to activity. These results suggest this technique a viable alternative to open ligation in paediatric urological practice.

Color Doppler ultrasound used for screening varicocele: the clinical significance as compared to physical examination.

The Acuson 128 XP color Doppler ultrasound (CDUS) unit has been applied to cases of infertility in the Chang Gung Memorial Hospital infertility clinic since November 1992. Seventy-four infertile males (group I) and 82 fertile cases (group II) with clinical obvious varicocele (detected by physical examination) were enrolled in this retrospective analysis. Subclinical varicocele (27%) may account for large group of the infertile men. It occurs almost bilaterally and can only be detected by CDUS. On the contrary, 26.8% of the cases with clinical obvious varicocele can be objectively ruled out by CDUS. Color Doppler ultrasound proved to be an easy, effective, convenient and noninvasive instrument for determining subclinical varicocele. It also helped to avoid unnecessary varicocelectomy in cases as judged by physical examination alone.

[Persistent varicocele: experience with prophilaxis and microsurgical treatment]. / Il varicocele persistente: nostra esperienza di profilassi e trattamento microchirurgico.

Persisting varicocele is still a rather hard clinical and therapeutical problem requiring a good level of surgical and microsurgical capability. In order to prevent and to treat postsurgical persistence, our trend is to resort to a correct and rational etiopathogenetical framing allowing us to choose the most appropriate surgical treatment. Relying on such procedure we perform all sorts of traditional and microsurgical interventions. We can say that the microsurgical techniques are the most appropriate ones to solve the problems of the second surgical intervention.

Percutaneous spermatic vein occlusion: evaluation of sclerosing agents in experimental animals.

The 5%-20% rate of recurrence of testicular varicoceles after embolotherapy has been a persistent clinical problem. Three sclerosing agents--sodium tetradecyl sulfate 3%, absolute ethanol, and 100 degrees C contrast material--were evaluated in canine spermatic veins for degree and durability of venous occlusion. Pathologic examination for perivenous, pulmonary, and neural changes was performed. Both sodium tetradecyl sulfate and absolute ethanol were effective sclerosants, but sodium tetradecyl sulfate was technically easier to use. The use of a sclerosant in conjunction with balloons or coils is the safest, most effective technique for occluding variococeles and minimizing postembolotherapy recurrences.