Comments on a class of orthogonality relations relevant to fluid-structure interaction

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Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear. Methodology and Principal Findings: Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3b, LC3B, Atg4, Atg5/12, Atg.7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1-1- mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema. Conclusions: We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. © 2008 Chen et al

The effects of sedation on gastric emptying and intra-gastric meal distribution in critical illness

The original publication can be found at www.springerlink.comObjectiveTo evaluate the effects of sedation with morphine and midazolam (M&M) versus propofol on gastric emptying in critically ill patients.DesignDescriptive study.SettingMixed medical and surgical intensive care unit.PatientsThirty-six unselected, mechanically ventilated, critically ill patients.InterventionsGastric scintigraphic data were analysed retrospectively according to whether patients were receiving M&M (n=20; 14M, 6F) or propofol (n=16; 7M, 9F). Measurements were performed over 4 h after administration of 100 ml of Ensure, labelled with 20 MBq Tc99m.Measurements and resultsGastric half-emptying time (t1/2) and total and regional (proximal and distal stomach) meal retention (%) were assessed. The median t1/2 of patients receiving M&M (153 (IQR: 72-434) min) was significantly longer than that of patients receiving propofol (58 (34-166) min, p=0.02). Total gastric retention was greater in patients receiving M&M compared to those receiving propofol (por=5% meal retention at 240 min than those treated with propofol (95% (19/20) vs. 56% (9/16); p=0.01). Changes in blood glucose concentrations during the study were similar in the two groups.ConclusionsIn critical illness, patients receiving M&M for sedation are more likely to have slow gastric emptying, and proximal meal retention than those receiving propofol. The apparent beneficial effects of propofol-based sedation need confirmation by a prospective randomised controlled study.Nam Q. Nguyen, Marianne J. Chapman, Robert J. Fraser, Laura K. Bryant, Carly Burgstad, Katrina Ching, Max Bellon and Richard H. Hollowa