Ozoile Reduces the LPS-Induced Inflammatory Response in Colonic Epithelial Cells and THP-1 Monocytes.

Inappropriate activation of immune functions in intestinal epithelial cells can lead to inflammation that is characterized also by infiltration into intestinal tissue of monocytes/macrophages. Current therapies for intestinal inflammation include anti-inflammatory, immunosuppressive and biological drugs. Ozoile (stable ozonides) has been reported to exert anti-inflammatory effects. However, ozonated oil has been used mainly for topical applications and no data are available about its effects on intestinal cells or immune cells. In this study, we evaluated Ozoile effects on human HT-29 colonic cells and THP-1 monocytic cells stimulated with LPS to induce inflammation. HT-29 and THP-1 cells were treated with LPS in the presence/absence of Ozoile for 4 h. Biomarkers of inflammation, some members of tight junctions and the adhesion molecule ICAM were assessed by qRT-PCR. Protein expression was analyzed by Western blotting. The release of TNF-α and IL-1ß was measured by ELISA. In HT-29, Ozoile inhibited LPS-induced expression of TNF-α, IL-1ß, ZO-1, CLDN1, NOS2 and MMP-2 and increased the expression of Nrf2 and SOD2 antioxidant proteins. In THP-1 cells, the LPS induction of TNF-α, IL-1ß and ICAM was counteracted by Ozoile treatment. Our in vitro results demonstrate the effectiveness of Ozoile in reducing the inflammatory response in intestinal and monocytic cells. Further in vivo studies are necessary to confirm its possible use for intestinal inflammatory conditions.

Pathogenesis of Congenital Malformations: Possible Role of Oxidative Stress.

OBJECTIVE: Congenital anomalies are important causes of morbidity and mortality in children. Oxidative stress (OS) is involved in the physiopathology of pregnancy-related congenital malformations. This review summarizes the role of OS in the pathogenesis of congenital malformations; in particular, its purpose is to describe how OS influences the development of heart congenital malformations, oesophageal atresia, biliary atresia, diaphragmatic hernia, and autosomal dominant polycystic kidney disease. STUDY DESIGN: Systematic review of previous studies about the role of OS in pregnancy and its possible effects in developing of congenital malformations. One electronic database (PubMed) was searched and reference lists were checked. RESULTS: An imbalance between the production of reactive oxygen species (ROS) and antioxidant defense can occur early in pregnancy and continue in the postnatal life, producing OS. It may destroy the signaling pathways needed for a correct embryogenesis leading to birth defects. In fact, cell functions, especially during embryogenesis, needs specific signaling pathways to regulate the development. These pathways are sensitive to both endogenous and exogenous factors; therefore, they can produce structural alterations of the developing fetus. CONCLUSION: Because OS plays a significant role in pathogenesis of congenital malformations, studies should be developed in order to better define their OS mechanisms and the beneficial effects of supplemental therapeutic strategies. KEY POINTS: · Oxidative stress is involved in the pathogenesis of congenital malformations.. · Heart malformations, oesophageal atresia, biliary atresia, diaphragmatic hernia, and autosomal dominant polycystic kidney are analyzed.. · A knowledge of pathomechanism of OS-related congenital malformations could be useful to prevent them..

CO2 pneumoperitoneum effects on proliferation and apoptosis in two different neuroblastoma cell lines.

PURPOSE: The proto-oncogene MYCN is considered a transcription factor involved in the regulation of neuroblastoma (NB) cell biology. Since minimally invasive-surgery represents a debated treatment of NB, we investigated CO2 effects on proliferative activity and apoptotic pathway in two NB cell lines, SH-SY5Y (MYCN-non-amplified) and IMR-32 (MYCN-amplified). METHODS: SH-SY5Y and IMR-32 were exposed to CO2 (100%) at a pressure of 15 mmHg for 4 h and then moved to normal condition for 24 h. Cell proliferation, caspase 3 activity and transcript levels of BAX, BCL-2, cyclin B, cyclin D and MMP-2 were evaluated. RESULTS: CO2 exposure caused a decrease in cell proliferation associated to increases in BAX/BCL-2 ratio and caspase 3 activity in SH-SY5Y, while opposite effects have been found in IMR-32. CO2 exposure induced a decrease of cyclin B1 in SH-SY5Y, while an increase in cyclin B1 and D1 was observed in IMR-32. A slight up-regulation of MMP-2 expression in SH-SY5Y and a significant increase of 2.2 folds in IMR-32 was observed (p < 0.05). CONCLUSIONS: Our results suggest that CO2 exposure may cause different effects on various NB cell lines, likely due to MYCN amplification status. Further in vitro and in vivo studies are needed to highlight the role of laparoscopy on NB behaviour.

Giammusso corporoplasty for the treatment of isolated congenital ventral penile curvature: Results and long-term follow-up.

The aim was to retrospectively evaluate our experience in a large series of patients affected by isolated congenital ventral penile curvature, surgically treated using a previously described modified incisional corporoplasty. Two hundred and six patients with isolated congenital ventral penile curvature underwent a modified incisional corporoplasty. Mean age at surgery was 20.7 ± 5.5 years, and degree of ventral curvature was 60 ± 23°. After the point of maximum convexity identification, Buck's fascia was vertically opened along the deep dorsal vein, which was partially ligated, resected and removed. Tunica albuginea was then longitudinally incised and transversally closed. Post-operative follow-up examination was performed at 2 weeks, 6, 12 and 24 months and then annually. Surgical time was 79 ± 12 min. At follow-up, 189 out of 198 patients (95%) were completely satisfied, four patients (2%) complained a recurrence of penile curvature, and 6 (3%) complained about shortening of the penis. None of the patients had any interference with sexual activity. One patient (0.5%) showed erectile dysfunction 5 years after surgery, but there was no organic dysfunction during examination. The proposed technique allows correction of ventral congenital penile curvature without dorsal neurovascular bundle manipulation, resulting in minimum trauma of the erectile tissue, without injury to nerve fibres.

Acute scrotal pain in pediatric patients: diagnosis with an innovative Doppler technique (MicroV).

Acute scrotal pain is one of the most frequent symptoms in pediatric patients visited in the Emergency Department. Ultrasonography with color and power Doppler represents the first-line method that clinicians use to carry out the differential diagnosis between spermatic cord torsion and inflammation, but sensitivity and specificity are 63-100% and 97-100%, respectively; this variability may be related to operator's experience and testis vascular hemodynamics and also to machine performance and patient age. Recent technological innovations have made possible to create a new Doppler mode called ultrasound microvascular imaging. This technique exploits algorithms capable of separating low frequencies of static tissue artifacts from ones of very weak flows. It is known as MicroV (from Esaote) and Superb microvascular imaging (from Toshiba). It provides both macrocirculation vascular maps, as a typical Doppler feature, and microcirculation vascular maps. Furthermore, the use of background subtraction could improve the visibility of small vascular structures. We report a case of a pediatric patient suffering from acute scrotal pain assessed ultrasonographically with this innovative Doppler technique (MicroV) that may give more confidence in detecting testicular vascular signals if compared with traditional Doppler techniques.

Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status.

Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, p16, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-MYCN-amplified) and IMR-32 (MYCN-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of HIF-1α in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of MYCN amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.

Methylene blue dye for identification of processus vaginalis during hydrocele repair: experience in a teaching hospital.

BACKGROUND: The aim of this study is to investigate the use of methylene blue in perioperative identification of the patent processus vaginalis in a group of boys presenting with congenital or recurrent hydrocele where surgery was performed by junior surgeons in training. METHODS: We retrospectively reviewed the notes of 22 boys with hydrocele, of which two recurrences, who were operated via a standard inguinal approach, by trainees. Methylene blue 0.3-0.5 mL was injected into the hydrocele fluid through the scrotal wall. A processus vaginalis was identified as a blue line. RESULTS: Methylene blue injection clearly identified a patent processus vaginalis in 91% of patients. In 9% (N.=2), of which one recurrence, methylene blue injection demonstrated a hydrocele with an obliterated processus vaginalis. There were no intraoperative complications. No testicular atrophy was recorded. CONCLUSIONS: Injection of methylene blue into the hydrocele sac may be considered a useful aid for a clearer identification of a difficult patent processus vaginalis. In the present series, there were no complications, and thus we believe that this technique might be suitable and especially helpful, in cases of recurrent hydrocele, and for junior surgeons in training.

The Risk For Malignancy of the Thyroid Nodule is Modulated by Gender, Echotexture, and Intranodular Lymphocytic Thyroiditis.

Based on the American (Bethesda, 2017) or Italian (SIAPEC 2014) cytological categories of thyroid nodules, the risk of malignancy and management vary. This risk is 5-10% or<3% (benign or TIR2), 6-18% or<10% (AUS/FLUS or TIR3A), 10-40% or 15-30% (FN/SFN or TIR3B), 45-60% or 60-80% (suspicious or TIR4), 94-96% or 95% (malignant or TIR5). In 408 thyroid nodules evaluated cytologically, we computed the malignancy rate in each category considering gender (325 females, 83 males), echotexture (268 isoechoic, 140 hypoechoic), intranodular chronic lymphocytic thyroiditis (ICLT: 113 with and 295 without); histology (263 benign, 145 malignant). It was 0-1.7% for the benign categories, except hypoechoic/ICLT+ve nodules of females (25%); 0-2.3% for the AUS/FLUS category, except isoechoic/ICLT-ve nodules of males (11.1%) and hypoechoic/ICLT-ve nodules of females (22.2%). For the FN/SFN category, rate was the most variable (from 0% in isoechoic/ICLT+ve nodules of males to 100% in hypoechoic/ICLT-ve nodules of males). The 30% threshold for risk was passed in four subgroups, and the 40% threshold in two subgroups (45% in isoechoic/ICLT-ve nodules of males, 80% in hypoechoic/ICLT+ve nodules of females). For the suspicious category, rate was 100% in males, except those with isoechoic/ICLT-ve nodules (75%), and>80% in females with hypoechoic nodules. For the malignant category, rate was always 100%. In conclusion, particular groups of nodules (based on gender, echotexture, and ICLT) within the cytologically benign through the suspiciously malignant category are at risk of malignancy substantially greater (even 100%) than the standard one. Accordingly, the suggested management cannot be standardized.

Similar effectiveness of dapagliflozin and GLP-1 receptor agonists concerning combined endpoints in routine clinical practice: A multicentre retrospective study.

AIMS: According to cardiovascular outcome trials, some sodium-glucose contransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are recommended for secondary cardiovascular prevention in type 2 diabetes (T2D). In this real-world study, we compared the simultaneous reductions in HbA1c, body weight and systolic blood pressure after initiation of dapagliflozin or GLP-1RA as second or a more advanced line of therapy. MATERIALS AND METHODS: DARWIN-T2D was a retrospective multi-centre study conducted at diabetes specialist clinics in Italy that compared T2D patients who initiated dapagliflozin or GLP-1RA (exenatide once weekly or liraglutide). Data were collected at baseline and at the first follow-up visit after 3 to 12 months. The primary endpoint was the proportion of patients achieving a simultaneous reduction in HbA1c, body weight and systolic blood pressure. To reduce confounding, we used multivariable adjustment (MVA) or propensity score matching (PSM). RESULTS: Totals of 473 patients initiating dapagliflozin and 336 patients initiating GLP-1RA were included. The two groups differed in age, diabetes duration, HbA1c, weight and concomitant medications. The median follow-up was 6 months in both groups. Using MVA or PSM, the primary endpoint was observed in 30% to 32% of patients, with no difference between groups. Simultaneous reduction of HbA1c, BP and SBP by specific threshold, as well as achievement of final goals, did not differ between groups. GLP-1RA reduced HbA1c by 0.3% more than the reduction achieved with dapagliflozin. CONCLUSION: In routine specialist care, initiation of dapagliflozin can be as effective as initiation of a GLP-1RA for attainment of combined risk factor goals.

Stable Ozonides with Vitamin E Acetate versus Corticosteroid in the Treatment of Lichen Sclerosus in Foreskin: Evaluation of Effects on Inflammation.

BACKGROUND: Lichen sclerosus (LS) is a disease of the skin of unclear etiology that can occur in the foreskin. Topical therapy with corticosteroids is recommended, but they can have side effects. OBJECTIVES: We aimed to compare the effects of ozonides with vitamin E acetate (OZOILE) versus topical corticosteroid in children undergoing circumcision. METHOD: Twenty children undergoing circumcision were treated before surgery: 10 children with OZOILE cream and 10 with 0.1% mometasone furoate once a day for 7 days. Ten age-matched patients with LS of the foreskin without any treatment were recruited as controls. Transcript levels of proinflammatory and anti-inflammatory cytokines and e-cadherin were evaluated in removed foreskins by qRT-PCR. RESULTS: OZOILE and steroid topical treatment produced a similar reduction of TNF-α and IL-1ß mRNA levels in foreskins from patients with LS when compared to untreated patients (p < 0.001). OZOILE and steroid treatment caused an increase in the transcript levels of IL-13 and e-cadherin in the foreskin of patients affected by LS in comparison to untreated foreskin (p < 0.001). CONCLUSIONS: On the basis of our biochemical data, a randomized clinical trial might be useful to verify the actual clinical effect of OZOILE as alternative treatment to corticosteroids in children affected by LS of the foreskin.

Altered Integrins Expression of Patients Affected by Cryptorchidism.

OBJECTIVES: The study aimed to investigate the expression of the integrin isoforms α7A and ß1A, expressed by myogenic precursor cells, and α7B and ß1D, expressed by mature muscle cells in the cremaster of patients affected by an undescended testis. METHODS: Fifteen samples of cremaster were obtained from patients undergoing surgery for an undescended testis. Thirty control specimens of cremaster were harvested from patients with congenital hydrocele or inguinal hernia. Immunofluorescent analysis was carried out using anti-α7A, ß1A, α7B, and ß1D integrin antibodies. Sections were observed using confocal laser scanning microscopy. RESULTS: As compared with controls, a significant loss of a α7B (p = 0.0355) and ß1D (p = 0.0069) integrins and a higher expression of α7A (p = 0.0003) and ß1A (p = 0.0150) was detected in the cremaster of patients affected by an undescended testis. CONCLUSIONS: Our data document a critical alteration of the cytoskeleton of cremasteric smooth muscle cells in patients with an undescended testis. This might explain the altered function in smooth muscle cells in cremaster implied during testicular descent. We therefore speculate that the postnatal splicing of α7A to α7B and of ß1A to ß1D integrins is delayed. This could account for the common clinical scenario of spontaneous descent of the testes in the first months of life.

Genetic analysis of the human insulin-like 3 gene in pediatric patients with testicular torsion.

PURPOSE: Testicular torsion (TT) mainly affects boys under 18 years old. To avoid orchiectomy, TT requires an immediate operative management. The etiology of TT is still controversial. Observed familiar recurrence suggests the presence of a genetic involvement. The INSL3 gene consists of two exons, and it is specifically expressed in fetal and adult Leydig cells. In transgenic mice, deletion of this gene was observed an increased testicular mobility and testicular torsion. We have hypothesized the possible involvement of the INSL3 gene as a predisposing factor of human TT. METHODS: We performed genetic analysis in 25 pediatric patients with unilateral and intravaginal TT (left, n = 13, 56%; right, n = 12, 48%). The age of the patients ranged from 1 to 16 years (median age n = 10.4 ± 5.46 years). In this study, we included two first male cousins affected by TT. Venous peripheral blood samples was obtained after parental written informed consent. RESULTS: The Thr60Ala polymorphism was detected in exon 1 of INSL3 gene and other 2 rarer variants (rs1047233 and rs1003887) were identified in the 3' untranslated region. These variants are prevalent in patients with TT instead of healthy subjects. CONCLUSIONS: Additional studies in a larger population are needed to better understand the clinical consequence of the INSL 3 variations founded. This would allow in the future to identify the patients at risk of TT to improve clinical management.

Anti-Inflammatory and Tissue Regenerative Effects of Topical Treatment with Ozonated Olive Oil/Vitamin E Acetate in Balanitis Xerotica Obliterans.

Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder, considered the male genital variant of lichen sclerosus. Anti-inflammatory drugs are commonly used in BXO. We evaluated the effects of an innovative formulation of ozonated olive oil with vitamin E acetate (OZOILE®) on the inflammatory status and tissue remodeling in male children with BXO. The mRNA transcripts of proteins involved either in inflammation or in dynamics of tissue regeneration were analyzed by quantitative real-time PCR, in foreskins affected by BXO removed from patients untreated or treated with OZOILE® cream for 7 days before circumcision. We found a significant reduction in mRNA levels of IL-1ß, TNF-α, INF-γ, transglutaminase 2 and NOS2 in foreskins treated with OZOILE® in comparison to untreated ones (p < 0.001). No significant differences were observed in NF-κB activation in the specimens obtained from treated and untreated patients. Hence, OZOILE® treatment up-regulated hypoxia-inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF) and E-cadherin gene expression (p < 0.001). The treatment with OZOILE® showed effective results in children affected by BXO by reducing the inflammatory process and stimulating mechanisms for tissue regeneration of the foreskin. A randomized clinical trial on a large number of children affected by BXO might be useful to verify the efficacy of topical treatment with OZOILE®.

Utility of uroflowmetry during the follow-up of children affected by balanitis xerotica obliterans (BXO).

INTRODUCTION: To evaluate the outcome of circumcised patients with balanitis xerotica obliterans (BXO) using uroflowmetry (UF). METHODS: Between 2011 and 2013, 180 children underwent a circumcision for phimosis. The foreskin was examined on microscopy. Patients with an histological diagnosis of BXO were included in the study. Patients with BXO underwent UF two weeks after surgery and treatment with clobetasol propionate ointment. Patients were re-evaluated at 6, 12, 18 and 24 months postoperatively clinically and using UF. RESULTS: 75 of 180 circumcised patients (41.6%) were included. At two weeks, Thirtytwo of 75 patients (42.7%) displayed a pathological UF. At six months, 15 patients (20%) had pathological UF and a new cycle of clobetasol was prescribed. At one year, 10 patients (13.3%) displayed patholgocial UF and underwent progressive urethral dilatation or meatoplasty. At 18 months, 71 patients (94.7%) displayed regular UF, 3 underwent a meatoplasty and one a staged urethroplasty for a severe urethral stenosis. At two years, UF was normal in 74 out of 75 (98.7%). CONCLUSIONS: We recommend to send for hystological examination all foreskins excised after circumcision. We believe that a clinical and uroflowmetric follow-up of pediatric patients with BXO is mandatory for a prompt identification of post-voiding dysfunction.

Premedication with melatonin vs midazolam: efficacy on anxiety and compliance in paediatric surgical patients.

Preoperative anxiety is a major problem in paediatric surgical patients. Melatonin has been used as a premedicant agent and data regarding effectiveness are controversial. The primary outcome of this randomized clinical trial was to evaluate the effectiveness of oral melatonin premedication, in comparison to midazolam, in reducing preoperative anxiety in children undergoing elective surgery. As secondary outcome, compliance to intravenous induction anaesthesia was assessed. There were 80 children undergoing surgery randomly assigned, 40 per group, to receive oral midazolam (0.5 mg/kg, max 20 mg) or oral melatonin (0.5 mg/kg, max 20 mg). Trait anxiety of children and their mothers (State-Trait Anxiety Inventory) at admission, preoperative anxiety and during anaesthesia induction (Modified Yale Pre-operative Anxiety Scale), and children's compliance with anaesthesia induction (Induction Compliance Checklist) were all assessed. Children premedicated with melatonin and midazolam did not show significant differences in preoperative anxiety levels, either in the preoperative room or during anaesthesia induction. Moreover, compliance during anaesthesia induction was similar in both groups. CONCLUSIONS: This study adds new encouraging data, further supporting the potential use of melatonin premedication in reducing anxiety and improving compliance to induction of anaesthesia in children undergoing surgery. Nevertheless, further larger controlled clinical trials are needed to confirm the real effectiveness of melatonin as a premedicant agent in paediatric population. What is Known: • Although midazolam represents the preferred treatment as a premedication for children before induction of anaesthesia, it has several side effects. • Melatonin has been successfully used as a premedicant agent in adults, while data regarding effectiveness in children are controversial. What is New: • In this study, melatonin was as effective as midazolam in reducing children's anxiety in both preoperative room and at induction of anaesthesia.

Polydeoxyribonucleotide Treatment in Genital Lichen Sclerosus in Males.

It has been reported that treatment with polydeoxyribonucleotide (PDRN) in males affected by lichen sclerosus significantly improves the overall conditions of treated patients. It confirms that PDRN has a potent cytoprotective action as in other pathological conditions. We believe that multicentric randomized clinical trials are necessary for testing the benefits of this promising agent.

Primary nocturnal enuresis: Assessment and treatment at a single referral center.

BACKGROUND: The aim of this study was to investigate the prevalence of primary monosymptomatic and non-monosymptomatic nocturnal enuresis (PMNE and PNMNE) and associated factors in a major referral center for NE in Abu Dhabi. METHODS: Children referred to the Paediatric Continence Clinic, between 2014 and 2016, for PNE were included in the study. Exclusion criteria were neuropathic bladder, abnormality of the bladder and bowel, urethral stenosis, neurological and psychiatric problems, non-completion of the diagnostic protocol, and follow up <6 months. RESULTS: A total of 128 patients were included in the study: 82 boys (64.1%) and 46 girls (35.9%). A total of 42.7% of boys and 8.7% of girls had PMNE, and 57.3% of boys and 91.3% of girls had PNMNE. Constipation was present in 46% of patients. In the male PNMNE group, 74.5% had overactive bladder (OAB), 10.6%, dysfunctional voiding (DV); and 14.9%, OAB + DV. In the female PNMNE group, 35.7% had OAB; 21.4%, DV; 40.5%, OAB + DV; and 2.4%, underactive bladder. A total of 97% and 86 of children with PMNE and PNMNE, respectively, had resolution of NE. Boys had a significantly higher incidence of PMNE, and girls, of DV. CONCLUSION: In Abu Dhabi, NE is often associated with bladder dysfunction or DV, mostly in girls, and with constipation. High intake of dry, low fiber foods, along with hot weather and the stress of city living negatively affect the incidence of fecal retention and of NE. A multimodal approach, including the treatment of constipation, led to a satisfactory resolution of PNE in almost 90% of cases.

Neonatal bowel strangulation: Rare presentation of congenital diaphragmatic hernia.

We report a case of congenital diaphragmatic hernia (CDH) with perinatal bowel strangulation requiring intestinal resection. Ten hours after birth, the newborn started to be lethargic and developed bilious emesis. X-ray documented distended loops of bowel with air fluid levels in the abdomen and a gasless, non-homogeneous opacity of the left hemithorax, a right mediastinal shift and loss of the sharp left hemidiaphram line. On gastrographin enema the left colon was above the adjacent left diaphragm. Emergency surgery was performed at 16 h of age. The entire small bowel appeared reddish and compromised. After 24 h, second-look laparotomy was performed and only 25 cm of small bowel were viable. The postoperative period was uneventful. Neonatal bowel strangulation in CDH should be taken into account when estimating postnatal morbidity and mortality and, even if CDH treatment is not an emergency procedure, if gastrointestinal symptoms prevail over respiratory symptoms, surgery should be carried out without delay.

Expression of Transglutaminase in Foreskin of Children with Balanitis Xerotica Obliterans.

Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder of unclear etiology. The etiology and the exact molecular mechanisms underlying the disease are still unknown. The human transglutaminase (TG) family consists of several proteins with catalytic activity essential for biological processes. In the present research we investigated the transcript levels of three TGs in patients operated on for congenital phimosis without or with histologically confirmed BXO; Thirty children with acquired phimosis were enrolled. The removed foreskins were sent both for histological diagnosis and for quantitative real-time PCR to evaluate the transcript levels of keratinocyte (TG1), tissue (TG2), and epidermal (TG3) transglutaminase; We observed a decrease in TG1 and TG3 transcripts by about 70% (p < 0.001) in foreskins from patients with BXO (n = 15) in comparison with patients without BXO (n = 15) and an increase in TG2 mRNA levels by 2.9 folds (p < 0.001); Reduced expression of both TG1 and TG3 was associated with the altered structure of the foreskin in BXO and can be a consequence of damage to keratinocytes. Increased expression of TG2 can be the result of chronic inflammation. TG2 overexpression can play a pivotal role in triggering and maintaining the inflammatory response in BXO patients.