American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jan 2009
Comparative StudyAntiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease.
Respiratory syncytial virus (RSV) is the most frequent cause of significant lower respiratory illness in infants and young children, but its pathogenesis is not fully understood. The transcription factor Nrf2 protects lungs from oxidative injury and inflammation via antioxidant response element (ARE)-mediated gene induction. ⋯ The results of this study support an association of oxidant stress with RSV pathogenesis and a key role for the Nrf2-ARE pathway in host defense against RSV.
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Am. J. Respir. Crit. Care Med. · Jan 2009
A once-weekly R207910-containing regimen exceeds activity of the standard daily regimen in murine tuberculosis.
R207910 (TMC207 or J) is a member of the diarylquinolines, a new family of antituberculous drugs with high bactericidal activity when given daily in the murine model of tuberculosis. R207910 exhibits a long half-life and thus is a good candidate for once-weekly therapy of tuberculosis. ⋯ The unprecedented activity of the triple combination of R207910 plus rifapentine plus pyrazinamide suggests that it may be feasible to develop a fully intermittent once-weekly regimen.
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Am. J. Respir. Crit. Care Med. · Jan 2009
High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling.
Phosphate (Pi) is an essential nutrient to living organisms. Recent surveys indicate that the intake of Pi has increased steadily. Our previous studies have indicated that elevated Pi activates the Akt signaling pathway. An increased knowledge of the response of lung cancer tissue to high dietary Pi may provide an important link between diet and lung tumorigenesis. ⋯ Our results showed that high dietary Pi promoted tumorigenesis and altered Akt signaling, thus suggesting that careful regulation of dietary Pi may be critical for lung cancer prevention as well as treatment.
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Am. J. Respir. Crit. Care Med. · Jan 2009
Surrogate decision-makers' perspectives on discussing prognosis in the face of uncertainty.
Many physicians are reluctant to discuss a patient's prognosis when there is significant prognostic uncertainty. ⋯ The majority of surrogates of patients that are critically ill want physicians to disclose their prognostic estimates even if they cannot be certain they are correct. This stems from surrogates' belief that prognostic uncertainty is simultaneously unavoidable and acceptable.
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Am. J. Respir. Crit. Care Med. · Jan 2009
Levosimendan enhances force generation of diaphragm muscle from patients with chronic obstructive pulmonary disease.
Levosimendan is clinically used to improve myocardial contractility by enhancing calcium sensitivity of force generation. The effects of levosimendan on skeletal muscle contractility are unknown. Patients with chronic obstructive pulmonary disease (COPD) suffer from diaphragm weakness, which is associated with decreased calcium sensitivity. ⋯ Levosimendan enhances force generating capacity of diaphragm fibers from patients with and without COPD patients by increasing calcium sensitivity of force generation. These results provide a strong rationale for testing the effect of calcium sensitizers on respiratory muscle dysfunction in patients with COPD.