Inhibiting lung lining fluid glutathione metabolism with GGsTop as a novel treatment for asthma.

Asthma is characterized by airway inflammation. Inflammation is associated with oxidant stress. Airway epithelial cells are shielded from this stress by a thin layer of lung lining fluid (LLF) which contains an abundance of the antioxidant glutathione.

Outcomes of a ventilator-associated pneumonia bundle on rates of ventilator-associated pneumonia and other health care-associated infections in a long-term acute care hospital setting.

Long-term trends in ventilator-associated pneumonia (VAP) rates, and other health care-associated infections, were examined prior to, during, and after introduction of a VAP bundle in a long-term acute care hospital setting. VAP incidence rate declined in a step-wise fashion and reached a null value. Incidence rates of bacteremia from any cause declined in a similar fashion.

Transcription factor Klf4, induced in the lung by oxygen at birth, regulates perinatal fibroblast and myofibroblast differentiation.

The fluid-filled lung exists in relative hypoxia in utero (∼25 mm Hg), but at birth fills with ambient air where the partial pressure of oxygen is ∼150 mm Hg. The impact of this change was studied in mouse lung with microarrays to analyze gene expression one day before, and 2, 6, 12 and 24 hours after birth into room air or 10% O(2). The expression levels of >150 genes, representing transcriptional regulation, structure, apoptosis and antioxidants were altered 2 hrs after birth in room air but blunted or absent with birth in 10% O(2).

Hyperoxia-induced lung injury in gamma-glutamyl transferase deficiency is associated with alterations in nitrosative and nitrative stress.

gamma-Glutamyl transferase (GGT) regulates glutathione metabolism and cysteine supply. GGT inactivation in GGT(enu1) mice limits cysteine availability causing cellular glutathione deficiency. In lung, the resultant oxidant burden is associated with increased nitric oxide (NO) production, yet GGT(enu1) mice still exhibit higher mortality in hyperoxia.

Epidemiology of ventilator-associated pneumonia in a long-term acute care hospital.

Objective: To characterize the epidemiology and microbiology of ventilator-associated pneumonia (VAP) in a long-term acute care hospital (LTACH).

Design: Retrospective study of prospectively identified cases of VAP.

Setting: Single-center, 207-bed LTACH with the capacity to house 42 patients requiring mechanical ventilation, evaluated from April 1, 2006, through January 31, 2008.

Lung lining fluid glutathione attenuates IL-13-induced asthma.

GGT(enu1) mice, deficient in gamma-glutamyl transferase and unable to metabolize extracellular glutathione, develop intracellular glutathione deficiency and oxidant stress. We used intratracheal IL-13 to induce airway inflammation and asthma in wild-type (WT) and GGT(enu1) mice to determine the effect of altered glutathione metabolism on bronchial asthma. WT and GGT(enu1) mice developed similar degrees of lung inflammation.

Regulation of Fgf10 gene expression in murine mesenchymal cells.

Fgf10 has a prominent role in organogenesis. In the developing lung, Fgf10 is dynamically expressed in the distal mesenchyme from where it diffuses and activates its epithelial receptor, Fgfr2b, to trigger budding. Little is known about how Fgf10 expression is regulated.

Fibulin-5 gene expression in human lung fibroblasts is regulated by TGF-beta and phosphatidylinositol 3-kinase activity.

Fibulin-5 (FBLN5), an extracellular matrix glycoprotein required for normal elastogenesis, is coordinately expressed with elastin during lung injury and repair. We found that treatment with transforming growth factor-beta (TGF-beta) induced a rapid but transient increase in FBLN5 heterogeneous nuclear RNA (hnRNA) followed by a sustained increased in the steady-state level of FBLN5 mRNA. The transcription start site of the human FBLN5 gene was localized at 221 nucleotides upstream of the translation start site by using primer extension, Northern blots, and functional analysis of transcriptional activity in reporter plasmids containing 5'-flanking regions.

Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in lung epithelial cells.

Aldolase C (EC 4.1.2.

Development and prospective validation of a model for predicting weaning in chronic ventilator dependent patients.

Background: Approximately ten percent of patients placed on mechanical ventilation during acute illness will require long-term ventilator support. Unfortunately, despite rehabilitation, some will never be liberated from the ventilator. A method of predicting weaning outcomes for these patients could help conserve resources and minimize frustrating failed weaning attempts for this population.

Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair.

Fibulin-5, previously known as DANCE and EVEC, is a secreted extracellular matrix protein that functions as a scaffold for elastin fiber assembly and as a ligand for integrins alphavbeta3, alphavbeta5, and alpha9beta1. Fibulin-5 is developmentally regulated in the lung, and lung air space enlargement develops in mice deficient in fibulin-5. Fibulin-5 is also induced in adult lung following lung injury by hyperoxia.

Gamma-glutamyl transferase deficiency results in lung oxidant stress in normoxia.

gamma-Glutamyl transferase (GGT) is critical to glutathione homeostasis by providing substrates for glutathione synthesis. We hypothesized that loss of GGT would cause oxidant stress in the lung. We compared the lungs of GGT(enu1) mice, a genetic model of GGT deficiency, with normal mice in normoxia to study this hypothesis.

DANCE in developing and injured lung.

We identified rat developing arteries and neural crest derivatives with multiple epidermal growth factor-like domains (DANCE) as a developmentally regulated gene using suppression-subtractive hybridization. Northern analysis confirmed a fivefold induction of this mRNA transcript between fetal day 18 and 20 that persisted through postnatal day 17. The level was declining at postnatal day 21 and was similar in adult lung to that at fetal day 18.