Background. Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies

Numerous therapies used for inflammatory bowel disease (IBD) target the transcription factor NF-κB, which is involved in the production of cytokines and chemokines integral for inflammation. Here we show that curcumin, a component of the spice turmeric, is able to attenuate colitis in the dinitrobenzene sulfonic acid (DNB)-induced murine model of colitis. When given before the induction of colitis it reduced macroscopic damage scores and NF-κB activation. This was accompanied by a reduction in myeloperoxidase activity, and using semiquantitative RT-PCR, an attenuation of the DNB-induced message for IL-1β was detected. Western blotting analysis revealed that there was a reproducible DNB-induced activation of p38 MAPK detected in intestinal lysates by using a phosphospecific antibody. This signal was significantly attenuated by curcumin. Furthermore, we show that the immunohistochemical signal is dramatically attenuated at the level of the mucosa by curcumin. We conclude that the widely used food additive curcumin is able to attenuate experimental colitis through a mechanism correlated with the inhibition of the activation of NF-κB and effects a reduction in the activity of p38 MAPK. We propose that this agent may have therapeutic implications for human IBD.

Rationale: Limited data on the epidemiology of acute respiratory distress syndrome (ARDS) using a standardized screening program exist. Objectives: To describe the population-based incidence of hypoxemic respiratory failure and ARDS using a prospective standardized screening protocol; and to describe the mechanical ventilation practice and the mechanical power and examine their association with 28-day and 3-year survival outcomes. Methods: A prospective standardized screening program for ARDS, as a quality improvement initiative, was initiated at four adult intensive care units over a 27-month period. An ancillary analysis of this observational cohort was performed. Patients requiring mechanical ventilation for ≥24 hours underwent prospective and consecutive screening using standardized ventilator settings. Patient physiological data and outcomes were collected prospectively through an electronic clinical-information system and retrospectively analyzed to apply Berlin criteria. Results: Screened were 7,944 patients, among which 986 (12.4%) had hypoxemic respiratory failure (arterial oxygen tension to inspired fraction of oxygen ratio ≤300), and 731 (9.2%) met criteria for ARDS. Age-adjusted incidence of hypoxemic respiratory failure and ARDS were 37.7 and 27.6 cases per 100,000 person-years, respectively. Patients sustaining the diagnosis of ARDS had a hospital mortality of 26.5% for mild, 31.8% for moderate, and 60.0% for severe ARDS and a 3-year mortality of 43.5% for mild, 46.9% for moderate, and 71.1% for severe ARDS. Mechanical power >22 J/min was associated with increased 28-day hospital and 3-year mortality. Determinants of mechanical power associated with lower 28-day hospital and 3-year survival included plateau pressure >30 cm H2O and driving pressure >15 cm H2O, but not tidal volumes >8 ml/kg of predicted body weight. Conclusions: Using standardized screening, a large proportion of patients with hypoxemic respiratory failure met criteria for ARDS. Increasing ARDS severity was associated with increased 28-day hospital and 3-year mortality. Increased mechanical power was associated with increased mortality. Potentially modifiable determinants of mechanical power associated with lower survival included plateau pressure and driving pressure.