Reactive oxygen species and chemokines： Are they elevated in the esophageal mucosa of children with gastroesophageal reflux disease？

AIM： To determine the role of inflammatory cytokines and reactive oxygen species （ROS） in childhood reflux esophagitis. METHODS： A total of 59 subjects who had complaints suggesting GERD underwent esophagogastroduoden oscopy. Endoscopic and histopathologic diagnosis of reflux esophagitis was established by Savary-Miller and Vandenplas grading systems, respectively. Esophageal biopsy specimens were taken from the esophagus 20% proximal above the esophagogastric junction for conventional histopathological examination and the measurements of ROS and cytokine levels. ROS were measured by chemiluminescence, whereas IL-8 and MCP-1 levels were determined with quantitative immunometric ELISA on esophageal tissue. Esophageal tissue ROS, IL-8 and MCP-1 levels were compared among groups with and without endoscopic/histo- pathologic esophagitis. RESULTS： Of 59 patients 28 （47.5%） had normal esophagus whereas 31 （52.5%） had endoscopic esophagitis. In histopathological evaluation, almost 73% of the cases had mild and 6.8% had moderate degree of esophagitis. When ROS and chemokine levels were compared among groups with and without endoscopic esophagitis, statistical difference could not be found between patients with and without esophagitis. Although the levels of ROS, IL-8 and MCP-1 were found to be higher in the group with histopathological reflux esophagitis, this difference was not statistically significant. CONCLUSION： These results suggest that the grade of esophagitis is usually mild or moderate during childhood and factors apart from ROS, IL-8 and MCP-1 may be involved in the pathogenesis of reflux esophagitis in children.     

The role of reactive oxygen species and apoptosis in the pathogenesis of varicocele in a rat model and efficiency of vitamin E treatment

We investigated role of reactive oxygen species (ROS) and apoptosis in the pathogenesis of infertility in experimental model of varicocele. The protective effect of vitamin E was also examined. Three groups of rats were constructed as the first group had sham operation, experimental varicoceles were established by partial ligation of the left renal vein in later two groups. Third group had received vitamin E. Production of ROS was determined by chemiluminescence assay (CL). The in situ end labelling technique was utilized to investigate apoptosis. Tissue vitamin E levels were measured by high performance liquid chromatography. The differences between luminol enhanced CL levels of groups were not statistically significant. However, the difference between CL levels of lucigenin probe in left testicles of sham and varicocele groups were statistically significant ( p = 0.0007). Similarly, the results of the third group receiving vitamin E significantly differed from the varicocele group ( p = 0.0025). The difference of apoptotic index was also statistically significant between sham and varicocele groups ( p = 0.0038). Although the values of apoptotic index detected in the vitamin E group were lower compared with the varicocele group, the difference was not significant. This study proposes that ROS production and apoptosis in the testicles were induced with experimental varicocele. Vitamin E had a protective role. An increased rate of apoptosis with experimental varicocele suggests a molecular alteration, which may involve ROS overproduction as the triggering mechanism. Consequently, this study indicates an association between varicocele and infertility at molecular level through stimulation of ROS and apoptosis.     

Rosiglitazone Attenuates Liver Inflammation in a Rat Model of Nonalcoholic Steatohepatitis

Rosiglitazone is an insulin-sensitizing agent. We aimed to assess the effects of rosiglitazone on a methionine- and choline-deficient diet (MCDD) model of nonalcoholic steatohepatitis (NASH) in rats. Wistar rats were fed either MCDD or a control diet in the 4-week induction study; they were given saline or 4 mg/kg/day rosiglitazone. After the induction study period, the rats were divided into four groups and fed MCDD or given a control diet for an additional 8 weeks and received saline or rosiglitazone. Serum and tissue samples were obtained. Rosiglitazone improved inflammation in NASH and improved ALT, alkaline phosphatase, and interleukin-6 levels in the induction study and interleukin-1β, interleukin-6, and tumor necrosis factor-α levels in the treatment study. Our preliminary study is the first to show the anti-inflammatory effects of rosiglitazone in NASH. Rosiglitazone’s effect on cytokines may be a key mechanism of its anti-inflammatory effect in NASH.     

Secukinumab and acitretin as a combination therapy for three clinical forms of severe psoriasis in multi‐drug refractory patients: A case series of high efficacy and safety profile

Secukinumab, the first monoclonal antibody that inhibits interleukin‐17A, has been shown to have rapid and long‐lasting efficacy in the treatment of moderate‐to‐severe psoriasis. However, there are still difficult‐to‐treat cases in which even dose‐escalation fails to provide a clinical response. In such cases, combining secukinumab with a conventional systemic agent may be a rational approach. Although methotrexate is most commonly preferred, acitretin may also be considered a good alternative, with its lower hepatotoxic potential. Data are limited regarding the use of combination therapy of secukinumab and acitretin for psoriasis. We herein present three patients with chronic plaque, generalized pustular and erythrodermic psoriasis, respectively, accompanied by multiple comorbidities, in whom skin clearance could not be achieved with several conventional and biologic therapies (including escalated dose regimens of secukinumab in two patients). Alternatively, we used a combination of secukinumab with low‐dose acitretin, which resulted in a complete or almost complete skin clearance in all patients, with no adverse events or increased toxicity. Based on our real‐life clinical experience with those patients, acitretin seems an effective and safe option to be used in combination with secukinumab. Even in patients who are refractory to multiple drugs including escalated doses of secukinumab, the addition of low‐dose acitretin may be helpful in achieving treatment goals, decreasing the need for switching to another biologic therapy.     

The effect of short- versus long-term administration of alpha tocopherol on the survival of random flaps in experimental diabetes mellitus

The effects of short- versus long-term alpha tocopherol administration on oxidative stress and survival of dorsal random flaps were studied in diabetic rats. Seven groups, with 20 rats in each, were constructed: (1) control, (2) noncontrolled diabetes, (3) noncontrolled diabetes+short-term alpha tocopherol, (4) noncontrolled diabetes+long-term alpha tocopherol, (5) insulin treatment, (6) insulin+short-term alpha tocopherol, and (7) insulin+long-term alpha tocopherol. After 3 months of diabetes, dorsal McFarlane flaps were raised. Flap viability and free-radical measurements with histopathological examination were investigated. Mean flap survival in Groups I to VII were 84.0+/-2.2%, 55.0+/-2.4%, 57.0+/-2.5%, 57.8+/-3.7%, 64.1+/-4.1%, 70.0+/-4.9%, and 77.0+/-6.6%, respectively. Free-radical concentration, as assessed with luminol- and lucigenin-enhanced chemiluminiscence, was inversely correlated with flap survival. The results for viability and free-radical concentrations were significant between Groups 1, 2, 5, 6, and 7. Random flaps in diabetic animals showed significantly greater necrosis compared with controls. Among the diabetic animals, group receiving combination of insulin and long-term alpha tocopherol treatment had the greatest flap viability and least tissue free-radical concentration. Histopathological studies showed a hyalinization of arterioles in diabetics with long-term alpha tocopherol treatment protecting the vessel wall. In conclusion, random flaps in experimental diabetes mellitus show greater tissue oxidative stress and necrosis, which is only partially corrected with insulin treatment. Long-term antioxidant supplementation as an adjunct to insulin further lowers the oxidative stress, protects vessel structure and function, and therefore increases flap survival.     

The efficacy of a novel antibacterial hydroxyapatite nanoparticle-coated indwelling urinary catheter in preventing biofilm formation and catheter-associated urinary tract infection in rabbits

The aim of this study was to investigate of the efficacy and reliability of a novel antimicrobial hydroxyapatite (HA) nanoparticle coating of urethral catheters, in the prophylaxis of biofilm formation and bacteriuria in rabbits. A total of 60 male rabbits were randomized to the control and study groups and each group was divided into three subgroups depending on 3, 5 and 7 days of the urethral catheterization period. The rabbits in the study group were catheterized with Ag⁺-incorporated nano-HA coated urethral catheters and those in the control group with standard silicon–latex urethral catheters. Urine and catheter surface smear samples were conducted for bacteriological analysis. Catheter cross-section samples were undergone measuring of biofilm thickness. Tissue samples of bladder and urethra were inspected for histological changes. The results indicate that at the end of 7 days of the catheterization period, the number of the rabbits with bacteriuria was significantly lower in the study group versus control group (p ^¶ = 0.020). The biofilm formation on luminal surface of the catheters was significantly thinner in the study group versus control group, at the end of 5 and 7 days of the catheterization period (0.035 and 0.035, respectively).No histological adverse change or particle penetration was detected in the urothelium. In conclusion, it was observed that Ag⁺ + HA nanoparticle coating significantly lowered the incidence of catheter-related bacteriuria and decreased biofilm formation, at the end of 7 days study period. The novel antimicrobial urethral catheter coating appeared to have a potential in the prophylaxis of catheter-induced urinary tract infections.     

Infliximab for the treatment of recalcitrant generalized pustular psoriasis of pregnancy: Report of a challenging case

Pustular psoriasis of pregnancy (PPP), also known as impetigo herpetiformis, is a rare gestational dermatosis that may induce life‐threatening complications for both the mother and fetus. Treatment of recalcitrant generalized PPP may be challenging as available therapeutic options are limited. We herein present a 24‐year‐old pregnant woman with generalized PPP accompanied by high fever, fatigue, leukocytosis, and elevated levels of serum acute phase reactants. The patient was resistant to a combination treatment of high‐dose cyclosporine (7.5 mg/kg/d, peroral), systemic methylprednisolone (1 mg/kg/d, intramuscular), and empirical antibiotherapy. However, she dramatically improved with infliximab (5 mg/kg, intravenous infusion), which was introduced at week 28 of pregnancy. Even within 24 hours after the first infusion of infliximab, pustular lesions began to regress with a rapid decline in fever. Following the third infusion, clearance of pustular lesions with a slight erythema was observed. Serum levels of leukocytes and acute phase reactants returned to normal. There were no adverse events related to infliximab therapy. At 40 weeks, the patient gave birth to a healthy baby. Our experience reported herein suggests that infliximab may serve as a rapidly acting, highly effective, and well‐tolerated “rescue” therapy in recalcitrant generalized PPP, which poses a big therapeutic challenge for clinicians.