Bis (2-butoxyethyl) Phthalate Delays Puberty Onset by Increasing Oxidative Stress and Apoptosis in Leydig Cells in Rats.

Objective: This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats. Methods: Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3ß pathways were assessed. Results: BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3ß and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 µmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05). Conclusion: BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.The graphical abstract is available on the website www.besjournal.com.

Dexmedetomidine impairs P­glycoprotein­mediated efflux function in L02 cells via the adenosine 5'­monophosphate­activated protein kinase/nuclear factor­κB pathway.

Dexmedetomidine (DEX) a type of the anaesthetic that has been widely used in anaesthesia and intensive care. However, whether DEX affects the pharmacokinetics of drugs remains elusive. As hepatic P­glycoprotein (P­gp) serves a critical role in the disposition of drugs, the present study aimed to address whether P­gp function could be affected by DEX in vitro. In the present study, L02 cells (a normal human liver cell line) were exposed to DEX for 24 h and P­gp function was evaluated by the intracellular accumulation of Rhodamine 123. The results indicated that P­gp function was significantly impaired by DEX treatment and that the mRNA levels and protein levels of P­gp were downregulated in a dose­ and time­dependent manner. Importantly, DEX­induced downregulation of P­gp was associated with adenosine 5'­monophosphate-activated protein kinase (AMPK) activation, as it was significantly attenuated by AMPK inhibition using dorsomorphin. Furthermore, the results revealed that changes in the subcellular localisation of nuclear factor (NF)­κB following AMPK activation were involved in the P­gp regulation in response to DEX treatment. Collectively, these results suggested that DEX impairs P-glycoprotein­mediated efflux function in L02 cells via the AMPK/NF­κB pathway, which provided direct evidence that the hepatic disposition of drugs may be affected by DEX through the downregulation of P­gp.

Clinical characteristics of Meckel diverticulum in children: A retrospective review of a 15-year single-center experience.

Meckel diverticulum is the most prevalent congenital abnormality of the gastrointestinal tract in children. The aim of this study was to review and analyze clinical data on the diagnosis and management of Meckel diverticulum in pediatric patients. The records of 102 pediatric patients (<14 years old) who underwent surgery for Meckel diverticulum at our institute between 2001 and 2015 were reviewed. Clinical, imaging, laboratory, surgical, and pathological data were recorded. The series comprised 65 males and 37 females with a median age of 5.6 years. Lower gastrointestinal bleeding was the most frequently identified clinical manifestation of Meckel diverticulum, and this manifestation was observed in 41 patients. Intussusception secondary to Meckel diverticulum was identified in 32 patients. Twelve patients presented clinical features of peritonitis; of these patients, 8 had perforated Meckel diverticulum and 4 had Meckel diverticulitis. In 10 patients, Meckel diverticulum was incidentally diagnosed during other surgeries, including appendectomy and neonatal enterostomy. Seven patients were diagnosed with intestinal obstruction. Technetium-99m pertechnetate imaging offered high diagnostic yield. Open surgery was performed on 59 patients, while a laparoscopic approach was employed in 35 patients. The remaining 8 patients did not undergo resection of the Meckel diverticulum. Histology revealed ectopic gastric mucosa in 42 patients (44.7%), ectopic pancreatic tissue in 35 patients (37.2%), mucosa of the small intestine in 15 patients (16.0%), and both gastric and pancreatic ectopic tissue in 2 patients (2.1%). All patients recovered uneventfully except 2 patients in whom an intestinal adhesion obstruction was identified after discharge. Meckel diverticulum had various clinical manifestations in children. Technetium-99m pertechnetate imaging may be useful for diagnosing Meckel diverticulum. Surgical excision of the Meckel diverticulum may be safe and effective in symptomatic patients, and relatively better outcomes can be achieved using this approach.

Transumbilical Single-Incision Laparoscopic Surgery in Children with Conventional Instruments: Our Early Experience.

OBJECTIVE: Laparoscopic surgery is the current accepted approach in most pediatric surgical centers. In an attempt to further minimize the surgical trauma and improve cosmetic outcome, new techniques with a single incision through the umbilicus have been proposed and we believe they will become the standard choices for pediatric surgery. This report describes our initial experience with transumbilical single-incision laparoscopic surgery (TSILS) in children with conventional instruments. MATERIALS AND METHODS: A retrospective review of 82 pediatric patients who underwent TSILS in children with conventional instruments from January 2011 to June 2015 was performed. The operations included 56 appendectomies, 9 cholecystectomies, and 17 spermatic vein ligations. RESULTS: The average age by procedure was 6.2 years for appendectomy (range of 3-14 years); 12.4 years for cholecystectomy (range of 10-14 years); and 12.8 years for spermatic vein ligation (range of 11-14 years). The average operative time was 32 minutes for appendectomy (range of 25-56 minutes); 54 minutes for cholecystectomy (range of 35-95 minutes); and 23 minutes for spermatic vein ligation (range of 17-41 minutes). The average length of staying in hospital was 3 days (range of 2-5 days). All of the operations in 82 cases were successful. None required conversion to open or conventional laparoscopic surgery. There was no obvious wound pain. In addition, there were no wound infections on umbilicus and any other intraoperative complications. There was no obvious scar at patients' umbilicus after postoperative follow-up for 2-4 weeks. CONCLUSIONS: TSILS is a safe and viable technique that may be used successfully in pediatric surgery. Additionally, excellent cosmetic results are obtained as evidenced by imperceptible umbilical scarring.

[Inhibitory effect of matrine on proliferation of human ovary malignant teratoma cell line PA-1 in vitro].

OBJECTIVE: To study the effect of matrine (MAT) on the proliferation of human ovary malignant teratoma cell line PA-1 in vitro. METHODS: PA-1 cells allocated in different groups were treated with different concentrations (0.25 mg/mL, 0.5 mg/mL and 1.0 mg/mL) of MAT. The inhibitory effect of MAT and its dose- and time-effect relationship were detected with MTT; the apoptosis rate and cell cycle were evaluated by flow cytometry; and the changes of bcl-2/bax mRNA expression in cells were measured using semi-quantitative RT-PCR. RESULTS: After being exposed to MAT, the PA-1 cell proliferation was decreased in a concentration- and time-dependent manner; cell apoptosis rate raised as the increasing concentration of MAT and acting time; cells retarded at G1 phase in the cell cycle dose-dependently; and the bcl-2/bax mRNA expression in cells dawn-regulated significantly. CONCLUSION: MAT can dose- and time-dependently inhibit the proliferation of PA-1 cell by reducing bcl-2/bax mRNA ratio to produce a G1 phase arresting in cell cycle.

[Effect of Safflor injection on the intestine ultrastructure characteristics following intestine ischemia/reperfusion injury in rabbits].

AIM: To explore effects of Safflor (Chinese Tradional Medicine) on the intestine ultrastructure characteristics during intestine ischemia/ reperfusion injury (I/RI) in rabbits. METHODS: Thirty rabbits were randomly divided into three groups: control group (group S), ischemia/reperfusion group (group I/R) and Safflor injection group (group SI). Morphological changes of intestine ischemia/reperfusion in rabbits and the protective effects of Safflor were observed under electric telescope. RESULTS: The intestine ultrastructure was badly injured in group I/R. Mitochondria and intestinal mucosal cells were swellen and endoplasmic reticulum expanded, however, in the SI group the ultrastructural injury of the ischemia greatly ameliorated. CONCLUSION: The ultrastructure injury occurrted after intestine I/RI and Safflor has protective effects on the intestine ultrastructure.

[Protective effects of inhibition of tissue nitric oxide in the initial stage against tardive injury of testicular spermatogenic function: experiment with rats].

OBJECTIVE: To study the protective effects of inhibition of tissue nitric oxide in the initial stage against the tardive injury of contralateral testicular spermatogenic function after unilateral testicular torsion. METHODS: 56 prepubertal Sprague-Dawley rats were randomly divided into 4 equal groups: placebo group undergoing rotation of left testis 720 degrees clockwise for 4 h, fixing thereof to the scrotum, and then intravenous injection of normal saline; cyclosporine group, undergoing intraperitoneal injection of cyclosporine once daily for 1 month after the testicular rotation and fixation; NG-methyl L-arginine (L-NMMA) group, undergoing intravenous injection of L-NMMA 30 mg/kg 30 min before the testicular rotation; and sham-operation group, undergoing isolation and suture of testis only. The right (untwisted) testes were removed from 7 rats from each group 1 week and 2 months after surgery. The malondialdehyde (MDA) level and nitrous oxide (NO)/nitrogen oxide synthase (NOS) content were evaluated. Histological examination was conducted. The mean seminiferous tubule diameter (MSTD) was assessed. The level of MHC peptide-tetramer complex was determined by flow cytometry. RESULTS: The levels of MDA, NO, NOS, and MHC peptide-tetramer complex of the L-NMMA, placebo, and cyclosporine groups one week after surgery were all significantly higher than those of the sham operation group (all P < 0.05). The levels of MDA, NO, NOS, and MHC peptide-tetramer complex of the L-NMMA group were all significantly lower then those of the placebo group (all P < 0.05). The pathological damage of the contralateral testis in early and late stages in the L-NMMA group was lighter than in the placebo group. CONCLUSION: By inhibiting tissue NO production in focal organizations during the early period, L-NMMA reduces the damages inthe testis contralateral to the testis undergoing unilateral torsion.