Gastroduodenal reflux induces group IIa secretory phospholipase A2 expression and activity in murine esophagus

Exposure of esophageal epithelium to gastric and duodenal contents results in the histologic changes of hyperproliferation and mucosal thickening. We have previously shown that presence of secretory phospholipase A₂ (sPLA₂) is necessary to produce these histologic changes in a murine model of gastroduodenal reflux. We sought to determine the influence of gastroduodenal reflux (GDR) on sPLA₂ protein and mRNA levels as well as enzyme activity in esophageal tissue. BALB/c (sPLA₂^+/+) mice (n= 28) underwent side‐to‐side surgical anastomosis of the first portion of the duodenum and GE junction (DGEA) resulting in continuous exposure of esophageal mucosa to mixed gastric and duodenal contents. Sham control mice (n= 14) underwent laparotomy, esophagotomy and closure. Real‐time RT PCR was used to quantitate the influence of GDR on group IIa sPLA₂ expression. Immunofluorescent staining was quantitated by digital microscopy using a specific antibody to identify and locate sPLA₂ protein. A colorimetric assay was used to quantify total sPLA₂ activity after standardization of protein levels. Statistical analysis was conducted using Student's t‐test. Group IIa sPLA₂ mRNA and protein levels were increased at 4 and 8 weeks compared with sham controls. This increase occurred in a time‐dependent manner and correlated with esophageal mucosal thickness. Furthermore, sPLA₂ enzyme activity was increased significantly at 4 and 8 weeks compared with untreated controls. The expression of group IIa sPLA₂ as well as sPLA₂ activity is induced by GDR. This novel finding indicates that sPLA₂ may play a role in the development of the histologic changes produced by GDR in esophageal mucosa.     

Postshock mesenteric lymph induces endothelial NF-kappaB activation

BACKGROUND: Posthemorrhagic shock mesenteric lymph (PSML) has been shown to activate pulmonary endothelial cells and cause lung injury. Although multiple mediators may be involved, most of these effects are mediated by nuclear factor-kappa B (NF-kappaB) activation. Degradation of the inhibitor of kappa B (IkappaB) is a key regulatory step in the activation of NF-kappaB. We therefore hypothesized that PSML would cause IkappaB degradation with subsequent NF-kappaB phosphorylation and nuclear translocation. METHODS: Mesenteric lymph was collected from male rats before shock and each hour after shock for up to 3 h (n = 5). Buffer (control), buffer + 10% (v/v) lymph, or buffer + tumor necrosis factor (10 ng/mL) were incubated with human pulmonary endothelial cells for 30 min and then lysed. Immunoblots of lysates were probed for IkappaB and phospho-p65. Immunohistochemistry was performed on cells grown on glass slides and then treated as above with the third PSML sample. Cells were fixed and then probed for p65. Statistical analysis was performed with Student's t-test and analysis of variance with significance was set at P < 0.05. RESULTS: Western blots of cell lysates for IkappaB demonstrated a steady decrease in total IkappaB with each lymph sample. Phosphorylation of NF-kappaB , p65 component, steadily increased with each PSML sample, with a maximum reached during the third PSML sample, which also significantly increased translocation of NF-kappaB to the nucleus. CONCLUSION: Postshock mesenteric lymph bioactivity is mediated by pathways which involved IkappaB degradation. These pathways offer novel off targets for clinical intervention to prevent the distal organ injury caused by postinjury hemorrhagic shock.     

Posttraumatic reactions among injured children and their caregivers 3 months after the terrorist attack in Beslan

This report describes symptoms of posttraumatic stress disorder (PTSD) among a group of Beslan's children (N=22) and their primary caregivers (N=20) 3 months after the children had been taken hostage in their school by a group of terrorists. Attention and memory were also measured. Children and their caretakers showed high levels of ongoing PTSD symptoms. Children also showed difficulties in sustaining attention and in short-term memory (digit span). These scores strongly indicate the need for appropriate interventions and ongoing monitoring of course of recovery.     

Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension

The objective of the present study was to analyze the impact of metabolic syndrome (MS) and its individual components on oxidative stress (OX) and on the activity of antioxidant enzymes of patients with essential hypertension. One hundred and eighty-seven hypertensives, 127 (61.9%) of them having criteria for MS according to the International Diabetes Federation criteria and 30 healthy normotensive subjects were included. OX status was assessed by measuring glutathione oxidized/glutathione reduced and reactive oxygen species-induced byproducts of lipid peroxidation, malondialdehyde, and DNA damage, 8-oxo-dG genomic and mitochondrial. Antioxidant enzymatic activity of Cu/Zn extracellular-superoxide dismutase (SOD) and catalase (CAT) was measured in plasma and glutathione peroxidase 1 in hemolysed erythrocytes. In mononuclear cells, total-SOD activity, CAT and glutathione peroxidase 1, were assessed as well. The OX state in both blood and peripheral mononuclear cells observed in hypertensives were not enhanced by the addition of components of the so-called MS. Likewise, the reduction in the activity of antioxidant enzymes, both extracellular and cytoplasmic, was not affected by the presence of additional components of the MS. Neither the number of components nor the individual addition of each of them, low high-density lipoprotein, triglycerides, abdominal obesity or fasting glucose, further impact in the OX abnormalities observed in those with only hypertension in absence of other components. In conclusion, the present data indicates that contribution of MS components to the OX burden generated by high blood pressure is minimal.     

Brief report: Self-blame and PTSD symptoms in adolescents exposed to terrorism: Is school connectedness a mediator?

Previous research has shown that self-blame predicts increased risk of posttraumatic stress disorder (PTSD) in youth exposed to terrorism, but little is known about the factors mediating such relationship. This study aimed to explore whether school connectedness (SC) mediates the effect of self-blame on PTSD in 60 adolescents (aged 14–18 years) who survived the 2004 terrorist attack against school no. 1 in Beslan, Russia. Participants completed measures of coping, SC, and PTSD three years after the traumatic event. Endorsement of self-blaming behaviors was found to be significantly positively related to the presence of PTSD; self-blame was negatively associated with SC, which in turn was negatively related to PTSD. The mediation hypothesis was supported, with SC partially mediating the link between self-blame and PTSD. Adolescents affected by terrorism may benefit from school-based interventions aimed at fostering students' sense of belonging and emotional bonding to teachers, peers, and the school environment.