Effect of hyperbaric oxygen and ulinastatin on plasma endotoxin, soluble CD14, endotoxin-neutralizing capacity and cytokines in acute necrotizing pancreatitis.

BACKGROUND: We sought to study the effect of a combination therapy comprised of hyperbaric oxygen (HBO) and ulinastatin on the plasma levels of endotoxin, soluble CD14 (sCD14), endotoxin neutralizing capacity (ENC) and cytokines in acute necrotizing pancreatitis (ANP) in rats. METHODS: We randomly allocated 90 Sprague-Dawley rats into 6 groups: group 1 (ordinary control), group 2 (sham operation), group 3 (ANP), group 4 (ANP with HBO), group 5 (ANP with ulinastatin) and group 6 (ANP with HBO and ulinastatin). We induced ANP by retrograde injection of 3.5% sodium taurocholate (2.5 mL/kg) via the pancreatic duct. Five minutes after induction, animals in groups 5 and 6 were infused with ulinastatin (20 000 U/kg) via the portal vein. Thirty minutes after induction, animals in groups 4 and 6 received HBO therapy. We collected samples 3, 6 and 10 hours after induction of ANP. RESULTS: We found that the plasma level of endotoxin in group 3 was significantly higher than in group 4 (3, 6 h, both p < 0.001), group 5 (3 h, p < 0.001; 6 h, p = 0.014) and group 6 (both p < 0.001). The level of plasma sCD14 in group 3 was significantly higher than in group 4 (3, 6 h, both p < 0.001), group 5 (3, 6 h, both p = 0.001) and group 6 (3 h, p < 0.001; 6 h, p = 0.001). The plasma endotoxin and sCD14 levels in group 6 were significantly lower than in groups 4 and 5. The plasma ENC level in group 6 was significantly higher than in groups 3, 4 and 5 (p < 0.001). The ENC level in groups 4 and 5 were higher than in group 3, but there was no significant difference. The plasma level of tumour necrosis factor-alpha (TNF-alpha) and IL-6 in group 6 were significantly lower than in groups 3, 4 and 5 (p < 0.001). The TNF-alpha and IL-6 levels in groups 4 and 5 were lower than in group 3, but there was no significant difference. CONCLUSION: The use of an early combination therapy of HBO and ulinastatin was more effective than either therapy alone in the treatment of ANP.

Effects of resveratrol and genistein on nuclear factor­κB, tumor necrosis factor­α and matrix metalloproteinase­9 in patients with chronic obstructive pulmonary disease.

Chronic airway inflammation and airway remodeling are the major pathophysiological characteristics of chronic obstructive pulmonary disease (COPD). Resveratrol and genistein have been previously demonstrated to have anti­inflammatory and antioxidative properties. The present study aimed to measure the inhibitory effects of resveratrol and genistein on tumor necrosis factor (TNF)­α and matrix metalloproteinase (MMP)­9 concentration in patients with COPD. Lymphocytes were isolated from the blood of 34 patients with COPD and 30 healthy subjects, then randomly divided into the following four treatment groups: Control, dexamethasone (0.5 µmol/l), resveratrol (12.5 µmol/l) and genistein (25 µmol/l) groups. After 1 h of treatment, 100 µl lymphocytes were collected for nuclear factor (NF)­κB immunocytochemical staining. After 48 h treatment, the supernatant of the lymphocytes was collected for analysis of TNF­α and MMP­9 concentration levels. The percentage of lymphocytes with positive nuclear NF­κB expression was analyzed by immunocytochemical staining. The concentration levels of TNF­α and MMP­9 were measured using radioimmunoassay and enzyme­linked immunosorbent assay, respectively. The present study demonstrated that the percentage of NF­κB­positive cells, and the levels of TNF­α and MMP­9 in lymphocytes from patients with COPD patients were significantly higher compared with healthy subjects. Additionally, there were positive correlations between the percentage of NF­κB­positive cells, and the concentration levels of TNF­α and MMP­9 in patients with COPD. All three factors were significantly reduced in lymphocytes treated with resveratrol and genistein, and the inhibitory effects of resveratrol on NF­κB, TNF­α and MMP­9 were more potent than the effects of genistein. In conclusion, resveratrol and genistein may inhibit the NF­κB, TNF­α and MMP­9­associated pathways in patients with COPD. It is suggested that resveratrol and genistein may be potential drugs candidates for use in the treatment of COPD.