Does lack of glutathione peroxidase 1 gene expression exacerbate lung injury induced by neonatal hyperoxia in mice?

Supplemental oxygen (O2) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasing glutathione peroxidase 1 (GPx1) gene expression increases the injurious effects of hyperoxia (Hyp). GPx1+/+ and GPx1-/- C57Bl/6J mice were exposed to 21% O2 (Air) or 40% O2 (Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pulmonary oxidative stress (P7d, P56d), macrophages in lung tissue (P7d), immune cells in bronchoalveolar lavage fluid (BALF; P56d), and GPx1-4 and catalase gene expression in lung tissue (P7d, P56d). On P7d, macrophages were decreased by lack of GPx1 expression and further decreased by hyperoxia. GPx1 expression was increased in GPx1+/+Hyp mice and decreased in both GPx1-/- groups. On P56d, heme oxygenase-1 was increased by hyperoxia when GPx1 was absent. There were significantly more immune cells from Hyp groups than from the GPx1+/+Air group and a greater proportion of lymphocytes in GPx1-/-Hyp mice. GPx1 expression was significantly decreased in GPx1-/- mice; GPx2-4 and catalase expression was increased in GPx1-/-Hyp mice compared with other groups. Tissue fraction was decreased in GPx1-/-Air mice; bronchiolar smooth muscle was decreased in GPx1-/- mice. GPx1 does not clearly exacerbate hyperoxia-induced increases in oxidative stress or lung injury but may alter pulmonary immune function. Increased expression of GPx2-4 and catalase in GPx1-/-Hyp mice suggests gene redundancy within the model.

Myocardial perfusion and oxidative stress after 21% vs. 100% oxygen ventilation and uninterrupted chest compressions in severely asphyxiated piglets.

AIM: Despite the minimal evidence, neonatal resuscitation guidelines recommend using 100% oxygen when chest compressions (CC) are needed. Uninterrupted CC in adult cardiopulmonary resuscitation (CPR) may improve CPR hemodynamics. We aimed to examine 21% oxygen (air) vs. 100% oxygen in 3:1 CC:ventilation (C:V) CPR or continuous CC with asynchronous ventilation (CCaV) in asphyxiated newborn piglets following cardiac arrest. METHODS: Piglets (1-3 days old) were progressively asphyxiated until cardiac arrest and randomized to 4 experimental groups (n=8 each): air and 3:1 C:V CPR, 100% oxygen and 3:1 C:V CPR, air and CCaV, or 100% oxygen and CCaV. Time to return of spontaneous circulation (ROSC), mortality, and clinical and biochemical parameters were compared between groups. We used echocardiography to measure left ventricular (LV) stroke volume at baseline, at 30min and 4h after ROSC. Left common carotid artery blood pressure was measured continuously. RESULTS: Time to ROSC (heart rate ≥100min(-1)) ranged from 75 to 592s and mortality 50-75%, with no differences between groups. Resuscitation with air was associated with higher LV stroke volume after ROSC and less myocardial oxidative stress compared to 100% oxygen groups. CCaV was associated with lower mean arterial blood pressure after ROSC and higher myocardial lactate than those of 3:1 C:V CPR. CONCLUSION: In neonatal asphyxia-induced cardiac arrest, using air during CC may reduce myocardial oxidative stress and improve cardiac function compared to 100% oxygen. Although overall recovery may be similar, CCaV may impair tissue perfusion compared to 3:1 C:V CPR.

Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure.

Preterm infants often require supplemental oxygen due to lung immaturity, but hyperoxia can contribute to an increased risk of respiratory illness later in life. Our aim was to compare the effects of mild and moderate levels of neonatal hyperoxia on markers of pulmonary oxidative stress and inflammation and on lung architecture; both immediate and persistent effects were assessed. Neonatal mice (C57BL6/J) were raised in either room air (21% O2), mild (40% O2), or moderate (65% O2) hyperoxia from birth until postnatal day 7 (P7d). The mice were killed at either P7d (immediate effects) or lived in air until adulthood (P56d, persistent effects). We enumerated macrophages in lung tissue at P7d and immune cells in bronchoalveolar lavage fluid (BALF) at P56d. At P7d and P56d, we assessed pulmonary oxidative stress [heme oxygenase-1 (HO-1) and nitrotyrosine staining] and lung architecture. The data were interrogated for sex differences. At P7d, HO-1 gene expression was greater in the 65% O2 group than in the 21% O2 group. At P56d, the area of nitrotyrosine staining and number of immune cells were greater in the 40% O2 and 65% O2 groups relative to the 21% O2 group. Exposure to 65% O2, but not 40% O2, led to larger alveoli and lower tissue fraction in the short term and to persistently fewer bronchiolar-alveolar attachments. Exposure to 40% O2 or 65% O2 causes persistent increases in pulmonary oxidative stress and immune cells, suggesting chronic inflammation within the adult lung. Unlike 65% O2, 40% O2 does not affect lung architecture.

Eating disorders and posttraumatic stress: phenomenological and treatment considerations using the two-factor model.

The incidence and impact of eating disorders and posttraumatic stress disorder (PTSD) are both profound. Recent data have suggested, however, that a possible concomitance may at times exist between the two diagnoses. The purpose of this paper is to increase awareness of the possibility that a presentation of an eating disorder may not be an isolated phenomenon, and it may be diagnostically prudent for clinicians to assess for a history of trauma and/or current trauma symptoms. For a clinician treating both diagnoses concurrently, we suggest utilizing the two-factor model of PTSD, and its natural corollary of neuropersonologic therapy, as a reasonable conceptual and treatment model.