p38 mitogen-activated protein kinase (MAPK) signaling is known to be increased in chronic obstructive pulmonary disease (COPD) macrophages. We have studied the effects of the p38 MAPK inhibitor N-cyano- pyrimidin-2-yl]amino}ethyl)guanidine (SB706504) and dexamethasone on COPD macrophage inflammatory gene expression and protein secretion. We also studied the effects of combined SB706504 and dexamethasone treatment. Lipopolysaccharide (LPS)-stimulated monocyte derived macrophages (MDMs) and alveolar macrophages (AMs) were cultured with dexamethasone and/or SB706504. MDMs were used for gene array and protein studies, whereas tumor necrosis factor (TNF) ␣ protein production was measured from AMs. SB706504 caused transcriptional inhibition of a range of cytokines and chemokines in COPD MDMs. The use of SB706504 combined with dexamethasone caused greater suppression of gene expression (Ϫ8.90) compared with SB706504 alone (Ϫ2.04) or dexamethasone (Ϫ3.39). Twenty-three genes were insensitive to the effects of both drugs, including interleukin (IL)-1␤, IL-18, and chemokine (CC motif ) ligand (CCL) 5. In addition, the chromosome 4 chemokine cluster members, CXCL1, CXCL2, CXCL3, and CXCL8, were all glucocorticoid-resistant. SB706504 significantly inhibited LPS-stimulated TNF␣ production from COPD and smoker AMs, with near-maximal suppression caused by combination treatment with dexamethasone. We conclude that SB706504 targets a subset of inflammatory macrophage genes and when used with dexamethasone causes effective suppression of these genes. SB706504 and dexamethasone had no effect on the transcription of a subset of LPS-regulated genes, including IL-1␤, IL-18, and CCL5, which are all known to be involved in the pathogenesis of COPD.Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and airway inflammation (Barnes, 2003). Alveolar macrophages (AMs) are believed to play a central role in disease pathogenesis by secreting proinflammatory cytokines and chemokines (Barnes, 2003). Glucocorticoids (GCs) are the most widely used

No abstract

As patient advocates, nurses are responsible for speaking up against unsafe practices. Nursing students must develop the confidence to speak up for patient safety so that they can hold themselves, as well as their peers and coworkers, accountable for patients' well-being. The purpose of this study was to examine the effects of a senior practicum course on confidence for speaking up for patient safety in nursing students. Confidence in speaking up for patient safety was measured with the Health Professional Education in Patient Safety Survey. The study showed a significant increase in nursing students' confidence after the senior practicum course, but there was no significant change in students' confidence in questioning someone of authority.

No abstract