American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jan 2016
Inhibition of mTOR Restores Corticosteroid Sensitivity in Chronic Obstructive Pulmonary Disease.
Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Several molecular mechanisms have been proposed, such as activations of the phosphoinositide-3-kinase/Akt pathway and p38 mitogen-activated protein kinase. However, the mechanism for corticosteroid resistance is still not fully elucidated. ⋯ mTOR inhibition by rapamycin restores corticosteroid sensitivity via inhibition of c-Jun expression, and thus mTOR is a potential novel therapeutic target for COPD.
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Am. J. Respir. Crit. Care Med. · Jan 2016
Randomized Controlled Trial Multicenter StudyRandomized Trial of Communication Facilitators to Reduce Family Distress and Intensity of End-of-life Care.
Communication with family of critically ill patients is often poor and associated with family distress. ⋯ Communication facilitators may be associated with decreased family depressive symptoms at 6 months, but we found no significant difference at 3 months or in anxiety or PTSD. The intervention reduced costs and length of stay, especially among decedents. This is the first study to find a reduction in intensity of end-of-life care with similar or improved family distress. Clinical trial registered with www.clinicaltrials.gov (NCT 00720200).
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Am. J. Respir. Crit. Care Med. · Jan 2016
Prostaglandin E2 Inhibits Neutrophil Extracellular Trap Formation Post-stem Cell Transplant.
Autologous and allogeneic hematopoietic stem cell transplant (HSCT) patients are susceptible to pulmonary infections, including bacterial pathogens, even after hematopoietic reconstitution. We previously reported that murine bone marrow transplant (BMT) neutrophils overexpress cyclooxygenase-2, overproduce prostaglandin E2 (PGE2), and exhibit defective intracellular bacterial killing. Neutrophil extracellular traps (NETs) are DNA structures that capture and kill extracellular bacteria and other pathogens. ⋯ Our results suggest blockade of the PGE2-EP2 or EP4 signaling pathway restores NETosis after transplantation. Furthermore, these data provide the first description of a physiologic inhibitor of NETosis.