A Comprehensive Review: Molecular and Genetic Background of Indirect Inguinal Hernias.

BACKGROUND: The occurrence of indirect inguinal hernias (IIH) is 5 times more prevalent than that of direct inguinal hernias (IH) and it is 7 times more common in males, owing to the attendance of the processus vaginalis (PV) throughout testicular descent. SUMMARY: In children, the immense mainstream of IH is indirect. The progress of IIH development in children is instigated with a patent PV, which is mostly treated by simple herniorrhaphy. Syndromes of the collagen, microfibril, elastin, and glycosaminoglycan constituents of the extracellular matrix may attend to the development of IH. Our recent research showed that the lack of epithelial-mesenchymal transition (EMT) in children contributes to the development of IIH, while the scenario is defined as the opposite in adults. However, there is still a lack of knowledge on all of the genetic and molecular causes of the disease. KEY MESSAGES: Here we aimed to review the published genetic background of IH, the deficiencies of connective tissue causing the disease, recently defined molecular pathways involved including EMT, and possible recurrence reasons. This comprehensive study can deliver an analytic outline aiding to define patients with IH combined with fundamental genetic diseases.

Deficiency of epithelial-mesenchymal transition causes child indirect inguinal hernia.

INTRODUCTION: Epithelial-mesenchymal transition (EMT) describes rapid changes in cellular phenotype. During EMT, epithelial cells down-modulate cell-cell adhesion, alter polarity, reorganize cytoskeleton, become isolated, motile, and resistant to anoikis. Epithelial breakdown and epithelial cell migration are the key processes involved in the obliteration of processus vaginalis. The great majority of abnormalities are because of nonobliteration or incomplete fusion of PV. We aimed to analyze the quantitative changes of epithelial genes in adult/child patients and their controls to examine differences of the genesis of these hernias. We also aimed to investigate the potential epigenetic causes of indirect inguinal hernia in adult patients. METHODS: Ten adult, ten child indirect inguinal hernia sacs and ten adult, ten child parietal peritonea were used. Hernial sac samples were obtained from indirect inguinal hernia surgeries. Peritonea of adult patients who underwent open cholecystectomy for cholelithiasis via subcostal incision were included in the study as the healthy control groups. Ages of the children were selected to be between 0 and 5 whereas the age of adults was chosen as 35-55, respectively. Total RNA isolation and cDNA synthesis were made from hernia sacs and peritoneum samples. Relative Keratin 1, Keratin 15, Filaggrin2 and STAT3 expressions were analyzed via qPCR. Indirect inguinal hernia sac cells were seeded and grown in vitro. Child diseased cells were employed in immunocytochemistry (ICC) analysis for Cytokeratin 15, Filaggrin2 and Bcl-2. Adult indirect inguinal hernia cells were examined for H3 modifications through ICC. RESULTS: In child indirect inguinal hernia, Keratin expressions were found higher than their controls. They were meaningfully lower than the healthy group in adult indirect inguinal hernia. Keratin 15, Keratin 1 and Filaggrin2 expressions were all correlating since they are members of related pathways. STAT3 expressions were opposite to Keratin and Filaggrin expressions suggesting that adult cells might have a switch to the mesenchymal state from the epithelial state. Adult indirect inguinal hernia samples have switched to the mesenchymal state whereas child indirect inguinal hernia samples have shown lack of transition. CONCLUSION: Irregular changes of EMT associated genes act in the progression of indirect inguinal hernia. Hence, the information on the epigenetic regulation of EMT in patients with primary inguinal hernia can aid to comprehend the pathogenesis in adults and infers new therapeutic approaches for this disease. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level 2.

A case of split notochord syndrome: Presenting with respiratory failure in the neonatal period.

Split notochord syndrome (SNS) is a very rare congenital anomaly. This report describes a male newborn with a neuroenteric cyst in the posterior mediastinum and multiple vertebrae anomalies presenting with respiratory failure and pulmonary hypertension. This report also discusses the embryological development and the etiologic theories of SNS.

Characterization and Differentiation of Stem Cells Isolated from Human Newborn Foreskin Tissue.

Circumcision is described as a cultural, medical, and religious process which states surgical removal of the foreskin either partly or fully. Cells isolated from the circumcised tissues are referred as foreskin cells. They have been thought as feeder cell lines for embryonic stem cells. Their fibroblastic properties were also utilized for several experiments. The waste tissues that remain after the circumcision thought to have stem cell properties. Therefore, there have been very few attempts to expose their stem cell properties without turning them into induced pluripotent stem cells. Although stem cell isolation from prepuce and their mesenchymal multilineage differentiation potential have been presented many times in the literature, the current study explored hematopoietical phenotype of newborn foreskin stem cells for the first time. According to the results, human newborn foreskin stem cells (hnFSSCs) were identified by their capability to turn into all three germ layer cell types under in vitro conditions. In addition, these cells have exhibited a stable phenotype and have remained as a monolayer in vitro. hnFSSCs suggested to carry different treatment potentials for bone damages, cartilage problems, nerve damages, lesion formations, and other diseases that are derive from mesodermal, endodermal, and ectodermal origins. Owing to the location of the tissue in the body and differentiation capabilities of hnFSSCs, these cells can be considered as easily obtainable and utilizable even better than the other stem cell sources. In addition, hnFSSCs offers a great potential for tissue engineering approaches due to exhibiting embryonic stem cell-like characteristics, not having any ethical issues, and teratoma induction as in embryonic stem cell applications.

Ischemia-reperfusion injury of rabbit ovary and protective effect of trapidil: an experimental study.

We aimed to detect the protective effect of trapidil in ischemia-reperfusion (IR) injury due to ovarian torsion and detorsion. Thirty-two pubertal New Zealand albino rabbits were used. Adnexal torsion was created by rotating the left adnexa including the tubal and ovarian vessels in a 360 degrees clockwise direction. Adnexal detorsion was done by untwisting the adnexa. In the IR group, left oopherectomy was performed after 3 h of adnexal torsion and 3 h of adnexal detorsion. In the study group, a 3-h adnexal torsion was performed and trapidil was administered intraperitoneally as a single dose of 40 mg/kg, 1 h before detorsion. The left oopherectomy was performed after a 3-h adnexal detorsion. In the sham group, sham operation was performed followed by left oopherectomy. In the control group, normal ovarian tissue was evaluated. Catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels of ovarian tissue were determined for each group. The values of SOD and GSH-Px activities in the IR group were significantly decreased (P < 0.05). In addition, the MDA level was significantly higher in the IR group (P < 0.01). The trapidil-administered group showed significant increase in the levels of GSH-Px (P < 0.05), catalase (P < 0.05), SOD (P < 0.05), and decreased MDA levels (P < 0.05) compared to those in the IR group. The study has shown that trapidil treatment prevents ischemia induced oxidative damage in the ovarian tissues of rabbits.

In vitro sensitivity of mouse esophagus to agonists in different pH medium values.

AIM: The aim of this study is to determine the in vitro sensitivity of mouse esophagus to contracting and relaxing agonists in different pH medium values. MATERIALS AND METHODS: Forty-eight Swiss albino mice (30-40 g) of both sexes were anesthetized with tiopental sodium (30 mg/kg). After exsanguinations from abdominal artery, esophagi were removed and suspended under 0.6 g of resting tension in a tissue bath containing 10 mL of Krebs solution at 37 degrees C. The experiments were performed in different pH mediums 7.4, 6.4, 4, and 2. Carbachol and acetylcholine were used as contractile agonists, and noradrenalin and isoproterenol to evaluate relaxation responses. Data concerning similar concentrations of contractile agonists obtained from different pH mediums were analyzed using Kruskal-Wallis nonparametric analysis of variance and post hoc Dunn test. Relaxation responses were compared with Student t test. A P value less than .05 was considered significant. The study was approved by Local Ethical Committee of Kirikkale University. RESULTS: Carbachol and acetylcholine caused concentration-dependent contractility in pH 7.4, 6.4, and 4, but contractile responses were inhibited in pH 2. In carbachol and acetylcholine experiments, there was a significant decrease in contractile responses to all concentrations in conjunction with a decreased in pH value. Relaxation responses in pH 2 and 4 could not be obtained because precontraction of tissues was not possible. Noradrenalin and isoproterenol produced concentration-dependent relaxations in pH 7.4 and 6.4. Although noradrenalin responses showed no significant difference according to pH, isoproterenol caused better relaxations in pH 6.4 (between 10(-8) and 10(-6) mol/L) when compared to pH 7.4 studies. CONCLUSION: The mouse esophagus has impaired contractile responses to carbachol and acetylcholine in decreased pH values. Contraction responses did not occur in pH medium of 2. In contrast, esophagus segments showed better relaxations in lower pH values with isoproterenol.

Protective effects of trapidil in ischemia-reperfusion injury due to testicular torsion and detorsion: an experimental study.

OBJECTIVE: We aimed to detect the preventive effects of trapidil in ischemia-reperfusion (IR) injury due to testicular torsion and detorsion. METHODS: Forty prepubertal albino rats were used. In the IR group, torsion was created by rotating the left testis over 2 h, and detorsion was done by untwisting the testis. Bilateral orchiectomies were performed after 4 h. In study group, 2-h torsion was performed and trapidil was administered as a single dose 1 h before detorsion. Bilateral orchiectomies were performed after 4 h. In the sham group, a sham operation was done. In the sham plus trapidil group, a sham operation was done and trapidil was administered as a single dose. Testicular tissue malondialdehyde (MDA), nitric oxide (NO) and total sulfhydryl (T-SH) levels were determined for each group. The grades of interstitial injury were determined in histopathologic examination. RESULTS: The NO and MDA levels in the IR group were significantly higher than the study, sham and sham plus trapidil groups in the left testis (P<0.05, P<0.001 and P<0.001, respectively). A statistical difference was not found among study, sham and sham plus trapidil groups in the left testis in NO and MDA levels (P>0.05). The T-SH level in the study group was significantly higher than in the IR, sham and sham plus trapidil groups in left testis P<0.05). In the IR group (left testis), grade 1 interstitial injury was 30% (3/10), grade 2 injury was 60% (6/10) and grade 3 injury was 10% (1/10). In the study group (left testis), grade 1 interstitial injury was 30% (3/10) and there was no injury in 70% (7/10). CONCLUSION: Trapidil decreased free oxygen radical formation in testicular torsion and detorsion, and attenuated histopathological damage in the ipsilateral twisted testis.

Embryologic preputial sinus remnant mimicking urethral duplication.

Urethral duplications are rare congenital anomalies. Approximately 200 cases of urethral duplications have been reported in literature. We present a seven-year-old-boy with an embryologic preputial sinus remnant which was mimicking urethral duplication. The clinical presentations and embryology of the urethral duplication and preputial sinus are discussed.

Effect of paralysis of the abdominal wall muscles by botulinum A toxin to intraabdominal pressure: an experimental study.

PURPOSE: To show the effect of botulinum A toxin-induced paralysis of abdominal muscles on intraabdominal pressure. MATERIAL AND METHODS: Fifteen Sprague-Dawley rats were divided into 2 groups. An abdominal skin incision was done, and 2 catheters were placed for the pressure monitoring and saline infusion. Saline solution was given to the abdomen until reaching to a pressure level of 9 cm H2O and 6 mm Hg in pressure device, and the amounts of injected saline were recorded. Then intraabdominal saline was drained. Two milliliters (5 U/mL) botulinum A toxin was applied to the abdominal muscles in group 2. Saline was injected at the same points in same amounts in group 1. After 3 days, catheters were placed, and the saline volumes needed to obtain the same pressure levels were recorded for each rat. Spontaneous motor unit potential (MUP), single MUP analysis and interference patterns of the muscles, respiratory rates, and vascular pressure measurements were recorded before and after botulinum toxin (Botox) injections. RESULTS: Mean intraabdominal saline volumes in the first and third days were 63.8 and 64.4 mL in group 1 and 67.6 and 80.6 mL in group 2, respectively. Mean MUP amplitude and duration of the rectus muscles in group 2 (17.1 microV and 1.47 milliseconds) were significantly lower than those of group 1 (187 microV and 4.9 milliseconds) in the third day. There were no pathological changes in respiratory rates and pressure measurements before and after Botox injections. CONCLUSION: This pilot experimental study showed that local injection of botulinum A toxin causes paralysis in abdominal wall muscles, increases the intraabdominal volume, and decreases the pressure, and this application may be used as an adjunct in abdominal wall closure in selective cases.

The effect of indwelling catheter on OH-proline in the urethral wound: an experimental study.

OBJECTIVE: To investigate the effect of catheterization on urethral wound healing by measuring OH-proline. METHODS: Eighteen male New Zealand albino rabbits were divided equally into three groups. In the control group, urethral tissue samples were taken from the ventral penile surface. In group II, the ventral penile surface was incised and primarily repaired by 6/0 polydioxanone. In group III, the incised urethra was repaired by 6/0 polydioxanone and a urethral catheter was inserted. Tissue samples were taken on the 20th postoperative day in groups II and III. Tissue OH-proline levels were measured by the method of Bergman and Loxley. The Kruskal-Wallis statistical test was used for evaluation. RESULTS: OH-proline values as microg/mg dry tissue were 16.43+/-2.68 in the control group, 14.47+/-1.82 in group II and 14.63+/-0.63 in group III. There was no significant difference between the three groups (P>0.05). CONCLUSION: Use of a urethral catheter does not appear to have a direct effect on collagen synthesis in wound healing.

Idiopathic benign bilateral testicular enlargement in a pubertal boy: a case report and review of literature.

We present a case of 12-year-old boy with idiopathic benign bilateral testicular enlargement. We eliminated precocious puberty, juvenile hypothyroidism, adrenal rest tumors, X-linked mental retardation, and bilateral testicular neoplasms. The clinical and laboratory features and differential diagnosis of benign bilateral testicular enlargement are discussed.

Trapidil, an inhibitor for phosphodiesterase and platelet-derived-growth factor, ameliorates corrosive esophageal burn in rats.

Corrosive esophageal burn is a common health problem in the pediatric age group and causes serious esophageal injuries. The medical treatment in acute phase of corrosive esophageal injury is of particular importance for prevention of esophageal stricture. We therefore aimed to investigate the possible beneficial effect of trapidil (triazolopyrimidine), an inhibitor for phosphodiesterase and platelet-derived-growth-factor, during acute phase of esophageal corrosive injury. Wistar albino rats were randomly allocated to untreated, treated, and sham-operated groups (n = 10 for each group). Corrosive esophageal burn was generated with 10% NaOH solution. The rats were left untreated (untreated group) or treated with trapidil as a single dose of 40 mg/kg intraperitoneally after one hour of the injury (treated group). Abdominal esophageal segment was isolated and tied in sham-control group. The studied esophageal segment was removed from each animal after 24 hours. Malondialdehyde (MDA) and nitric oxide (NO) levels were measured in the esophageal tissues. The ulcer depth was graded by histopathologic examination. MDA and NO levels were significantly higher in the untreated group than in the treated group. Namely, trapidil treatment significantly decreased MDA and NO levels in the injured tissues, the levels of which are similar to those in the tissues of control animals. The grades of ulcer depth were significantly improved in the treated group. These results indicate that the reactive oxygen radicals increase in the early phase of corrosive esophagitis and cause tissue damage. We suggest that trapidil treatment may be useful in acute phase of corrosive esophageal injury.

Protective effects of trapidil in lung after abdominal aorta induced ischemia-reperfusion injury: an experimental study.

UNLABELLED: We aimed to investigate the protective effects of trapidil after the occlusion of abdominal aorta and the reperfusion injury in lung. Eighteen New Zealand albino rabbits were used in the study. In six animals [group 1, ischemia-reperfusion (IR) group], the abdominal aorta was exposed and a microvascular clamp was placed in the infrarenal abdominal aorta for 60 min. After the ischemic period, the microvascular clamp was removed and reperfusion was provided for 2 h. After the reperfusion period, the lungs were removed carefully and specimens were prepared for histopathological and biochemical studies in appropriate conditions. In group 2 (study group), trapidil (Rocarnal, Rentschler-UCB GmbH, Kerpen, Germany) was administered intraperitoneally as a single dose 1 h prior to trial, the IR procedure was performed and lung specimens were prepared similar to group 1. In group 3 (sham group), the infrarenal abdominal aorta was exposed and lung specimens were prepared for histopathological and biochemical studies at the end of the study. Histopathological changes, malondialdehyde (MDA), nitric oxide (NO) and total sulfhydryl group (T-SH) levels were evaluated. There was a statistical difference between the IR group and study group regarding NO and MDA levels (P < 0.05 and P < 0.01, respectively), but this was not detected between the IR group and the sham group (P > 0.05). There was no statistical difference among the three groups regarding T-SH levels (P > 0.05). While a statistical difference was found between the sham group and study group in the NO level (P < 0.05), no statistical difference was found in the MDA level (P > 0.05). There was a statistical difference in interstitial edema, PMN infiltration and hemorrhage scores among the groups (P < 0.05). There was a statistical difference between the IR group and study group in PMN infiltration (P < 0.05), but this was not detected between the groups in interstitial edema and hemorrhage scores (P > 0.05). There was a statistical difference between IR group and sham group in interstitial edema, PMN infiltration and hemorrhage scores (P < 0.05). Statistical difference was found between the sham group and study group in interstitial edema and hemorrhage scores (P < 0.05), but not in PMN infiltration (P > 0.05). CONCLUSIONS: Infrarenal abdominal aortic occlusion and reperfusion causes lung injury. We conclude that trapidil has preventive effects in the lung tissue after IR injury.

Autorevascularization of the testicle and spermatic vessels by bladder pedicle flap: an experimental study.

PURPOSE: The aim of the study was to investigate revascularization of the testicle through its own tissue and spermatic vessels by a bladder pedicle flap in rabbits. METHODS: Thirty male rabbits were used in the study. In 10 animals, the Fowler-Stephens (FS) procedure was applied to the right testicles (FS group). The FS procedure and revascularization of the testicle by a bladder pedicle flap were applied to the right testicles in 10 animals (FSO group). No surgical procedure was performed in the control group. Scintigraphic study was performed 3 weeks after the high ligation procedure in the FS and FSO groups. Both testicles were evaluated by radionuclide scintigraphy in all the animals. Macroscopic testicle weights were evaluated. Testicular biopsy scores and mean seminiferous tubule diameters were determined in the histopathologic study. RESULTS: The testicular blood flow of the FSO group was better than the FS group (P < .05), but there was no statistically significant difference between the FSO and the control groups (P > .01). Testicle weights, testicular biopsy scores, and seminiferous tubule diameters in the FSO group were detected, and there was a statistically significant difference when compared with the FS group (P < .05) but not with the control group (P > .01). CONCLUSION: We suppose that the surgical model of revascularization of the testicle through its own tissue and spermatic vessels by a bladder pedicle flap can be an alternative to the FS procedure in abdominal and high canalicular undescended testicles.