Protection of pulmonary epithelial cells from oxidative stress by hMYH adenine glycosylase.

BACKGROUND: Oxygen toxicity is a major cause of lung injury. The base excision repair pathway is one of the most important cellular protection mechanisms that responds to oxidative DNA damage. Lesion-specific DNA repair enzymes include hOgg1, hMYH, hNTH and hMTH. METHODS: The above lesion-specific DNA repair enzymes were expressed in human alveolar epithelial cells (A549) using the pSF91.1 retroviral vector. Cells were exposed to a 95% oxygen environment, ionizing radiation (IR), or H2O2. Cell growth analysis was performed under non-toxic conditions. Western blot analysis was performed to verify over-expression and assess endogenous expression under toxic and non-toxic conditions. Statistical analysis was performed using the paired Student's t test with significance being accepted for p < 0.05. RESULTS: Cell killing assays demonstrated cells over-expressing hMYH had improved survival to both increased oxygen and IR. Cell growth analysis of A549 cells under non-toxic conditions revealed cells over-expressing hMYH also grow at a slower rate. Western blot analysis demonstrated over-expression of each individual gene and did not result in altered endogenous expression of the others. However, it was observed that O2 toxicity did lead to a reduced endogenous expression of hNTH in A549 cells. CONCLUSION: Increased expression of the DNA glycosylase repair enzyme hMYH in A549 cells exposed to O2 and IR leads to improvements in cell survival. DNA repair through the base excision repair pathway may provide an alternative way to offset the damaging effects of O2 and its metabolites.

Intensive care management of the patient with cystic fibrosis.

Cystic fibrosis was previously thought to be a disease of childhood. With a better understanding of this condition along with improvements in therapy, patients with cystic fibrosis are now living well into adulthood. The aim of this article is to familiarize the intensive care unit physician with cystic fibrosis care, to discuss complications associated with cystic fibrosis specifically related to the intensive care unit, and to detail the current recommendations for the clinical management of the patient with cystic fibrosis. With advancing disease, the most severely affected organs are the lungs. Obstruction, infection, and inflammation contribute to the decline of pulmonary function, ultimately leading to death. Some patients may be eligible for lung transplantation, but choosing wisely will affect posttransplant survival. Because other organs are affected by the genetic defect and associated treatments, serious complications related to the liver, pancreas, intestines, and kidneys must be considered by the intensivist faced with a patient with cystic fibrosis. As practitioners, the fact that not all patients will survive and help our patients and families gracefully through the end-of-life process should be accepted.