Overexpression of Extracellular Superoxide Dismutase Protects against Brain Injury Induced by Chronic Hypoxia

Extracellular superoxide dismutase (EC-SOD) is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1%) for 10 days (H-KI) and compared to transgenic animals housed in room air (RA-KI), wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT). Overall brain metabolism evaluated by positron emission tomography (PET) showed that H-WT mice had significantly higher uptake of (18)FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation

Gastroesophageal Reflux Characteristics and Patterns in Patients with Idiopathic Subglottic Stenosis

Introduction. Idiopathic subglottic stenosis represents a spectrum of subglottic disease without a clear underlying cause. Prior studies have implicated a pathogenic role of gastroesophageal reflux disease in idiopathic subglottic stenosis. The aim of this study was to examine the presence and pattern of gastroesophageal reflux in a large cohort of patients with idiopathic subglottic stenosis at a tertiary referral center. Methods. We performed a retrospective review of patients with idiopathic subglottic stenosis from January 2010 to December 2016 who had undergone combined pH impedance testing. Patients with prior gastric or esophageal surgery were excluded. Data obtained included esophageal acid exposure times, number of reflux events, patient position during reflux events (defined as upright, supine, or mixed), body mass index, and the presence of proton pump inhibitor therapy. Results. 159 patients with the idiopathic subglottic stenosis were identified, of whom 41 had undergone esophageal pH impedance testing. 40 (97.6%) were women, with a mean age of 54.8 (range 31–79) years and BMI of 31.0 (range 17–55). Overall, 19 (46.3%) patients were found to reflux as confirmed by abnormal esophageal acid exposure or abnormal number of reflux events. 15 of the 19 patients with reflux had predominantly upright gastroesophageal reflux disease, whereas 2 had supine and 2 mixed reflux. Discussion. In patients with idiopathic subglottic stenosis who underwent evaluation by combined pH impedance, close to half were found to have gastroesophageal reflux disease. The majority of gastroesophageal reflux occurred while the patients were in the upright position

Relationship Between Milk Fat Globule-Epidermal Growth Factor 8 and Intestinal Cytokines in Infants Born Preterm.

OBJECTIVES:To investigate the relationships between dietary intake and fecal concentrations of milk fat globule-epidermal growth factor 8 (MFG-E8), and between fecal concentrations of MFG-E8 and markers of intestinal inflammation in infants born preterm. STUDY DESIGN:Fecal samples were collected daily and enteral feedings were sampled weekly. MFG-E8 in enteral feedings and feces, and cytokine concentrations in feces were quantified by ELISA. RESULTS:Milk MFG-E8 concentrations were significantly greater in unfortified mother\u27s own milk (MOM) and fortified mother\u27s own milk (MOM+HMF) than either donor human milk or preterm formula. MFG-E8 concentrations in fecal samples were positively correlated with MFG-E8 concentrations in respective milks. High MFG-E8 exposure (\u3e60 mL/kg/day of feedings that include MOM or MOM+HMF) was associated with lower concentrations of pro-inflammatory cytokines (interleukin-8, tumor necrosis factor-α, and monocyte chemoattractant protein-1) and higher concentrations of the anti-inflammatory cytokine interleukin-4 in feces, compared with low MFG-E8 exposure. CONCLUSION:Infants born preterm who were fed MOM had greater concentrations of MFG-E8 and lower concentrations of pro-inflammatory cytokines in fecal samples than other diets or no feedings. These data further support the protective role of MOM, possibly due to MFG-E8, against intestinal inflammation

Bacterial stability with freezer storage of human milk

© 2020 De Gruyter. All rights reserved. Human milk supports the development of a beneficial newborn intestinal microflora. We have shown previously that human milk had reduced bacteria but unchanged nutrient composition when stored at -20 °C for up to nine months. We suspected declining bacterial colony counts were manifestations of bacterial dormancy and not failure of survival. We investigated differences in selected bacterial colony counts (lactobacillus, bifidobacteria, staphylococcus, streptococcus and enterococcus) in human milk stored for 2 and 12 weeks at -20 °C in either manual or automatic defrost freezers and whether reduced bacterial counts at 12 weeks were the result of dormancy or failure of survival. Freshly expressed milk was obtained from mothers in the NICU, divided into aliquots and stored for 2 and 12 weeks at -20 °C in either automatic or manual defrost freezers. Subsequently, duplicate aliquots, one thawed and the other thawed and maintained at room temperature for 4 h, were plated to assess bacterial colony counts. Significant declines in bacterial colony counts were seen from 2 to 12 weeks freezer storage for all bacteria. There were no differences in colony counts between freezer types. Once thawed, no further bacterial growth occurred. Short-term freezer storage for 12 weeks resulted bacterial killing. Type of freezer used for storage did not have an impact on bacterial survival. It is unknown whether the paucity of important probiotic bacteria in stored human milk has adverse effects on infants

Effects of human milk fortifier properties on intrinsic probiotic bacteria

© 2020 Walter de Gruyter GmbH, Berlin/Boston. To meet the nutritional needs of preterm infants, multicomponent nutrient fortifiers are added to human milk. The fortified human milk (FHM) product changes the physical and biochemical characteristics of the milk. We questioned whether such physical-chemical changes in the milk would alter intrinsic probiotic bacterial activity. The objective of the study was to evaluate the effect of osmolality and pH on the growth of probiotic bacterial species intrinsic to human milk. Human milk samples (n = 26) were collected from mothers in the neonatal intensive care unit (NICU) and stored at-20°C until analyzed. The samples were thawed and divided into three portions. Human milk fortifiers (HMFs) were added to two portions to prepare concentrations of FHM. The remaining portion was the unfortified control sample. Each sample was then divided into two parts. One part (baseline) was used to measure the osmolality and pH and plated on selective agar to enumerate the growth of lactobacilli and bifidobacteria species. The remaining part was incubated at 37°C for 24 h to further test bacterial integrity (post-incubation) and then the same measurements were made (osmolality, pH, bacterial colony counts). When compared with unfortified milk at baseline, osmolality increased and pH decreased significantly after the addition of HMFs. Lactobacilli and bifidobacteria colony counts did not differ among the groups pre-incubation. Post-incubation lactobacilli and bifidobacteria increased in all the groups. The appropriate addition of HMFs differentially affected the osmolality and pH of the milk. These physical changes did not affect the growth of probiotic bacterial species