Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis.

BACKGROUND: Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. METHODS: Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. RESULTS: A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). CONCLUSIONS: A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.

Prolonged mechanical ventilation induces pulmonary inflammation in preterm infants.

Lung inflammation plays an important role in the pathogenesis of chronic lung disease in preterm infants. To test the hypothesis that prolonged mechanical ventilation induces pulmonary inflammation, we analyzed pro- and anti-inflammatory mediators in bronchoalveolar lavage fluid obtained from ventilated preterm infants having respiratory distress syndrome. Our results show a strong correlation between the duration of mechanical ventilation and the amount of proinflammatory mediators. However, the anti-inflammatory cytokine interleukin 10 remained stable during the whole period of mechanical ventilation. These data support the hypothesis that prolonged mechanical ventilation contributes to the development of chronic lung disease by the induction of lung inflammation without adequate stimulation of the counterregulatory cytokine interleukin 10 in preterm infants with respiratory distress syndrome.

Treatment with bovine surfactant in severe acute respiratory distress syndrome in children: a randomized multicenter study.

OBJECTIVE: To determine whether bovine surfactant given in cases of severe pediatric acute respiratory distress syndrome (ARDS) improves oxygenation. DESIGN: Single-center study with 19 patients, followed by a multicenter randomized comparison of surfactant with a standardized treatment algorithm. Primary endpoint PaO(2)/FIO(2) at 48 h, secondary endpoints: PaO(2)/FIO(2) at 2, 4, 12, and 24 h, survival, survival without rescue, days on ventilator, subgroups analyzed by analysis of variance to identify patients who might benefit from surfactant. SETTING: Multicenter study in 19 reference centers for ARDS. PATIENTS: Children after the 44th postconceptional week and under 14 years old, admitted for at least 4 h, ventilated for 12-120 h, and without heart failure or chronic lung disease. In the multicenter study 35 patients were recruited; 20 were randomized to the surfactant group and 15 to the nonsurfactant group. Decreasing recruitment of patients led to a preliminary end of this study. INTERVENTIONS: Administration of 100 mg/kg bovine surfactant intratracheally under continuous ventilation and PEEP, as soon as the PaO(2)/FIO(2) ratio dropped to less than 100 for 2 h (in the pilot study increments of 50 mg/kg as long as the PaO(2)/FIO(2) did not increase by 20%). A second equivalent dose within 48 h was permitted. RESULTS: In the pilot study the PaO(2)/FIO(2) increased by a mean of 100 at 48 h (n=19). A higher PaO(2)/FIO(2) ratio was observed in the surfactant group 2 h after the first dose (58 from baseline vs. 9), at 48 h there was a trend towards a higher ratio (38 from baseline vs. 22). The rate of rescue therapy was significantly lower in the surfactant group. Outcome criteria were not affected by a second surfactant dose (n=11). A significant difference in PaO(2)/FIO(2) in favor of surfactant at 48 h was found in the subgroup with an initial PaO(2)/FIO(2) ratio higher than 65 and in patients without pneumonia. CONCLUSIONS. Surfactant therapy in severe ARDS improves oxygenation immediately after administration. This improvement is sustained only in the subgroup of patients without pneumonia and that with an initial PaO(2)/FIO(2) ratio higher than 65