ABSTRACT
BACKGROUND: The role of polymorphonuclear neutrophil granulocytes (PMNs) and the PMN-derived protease, which is called matrix metalloproteinase-9 (MMP-9), for the gut barrier dysfunction in severe acute pancreatitis (SAP) has not yet been clarified. The aim of this study was to evaluate the effects of PMNs and MMP-9 on gut barrier dysfunction in rat SAP. METHODS: SAP was induced by the injection of 5% sodium taurocholate, and anti-rat PMN serum or BB-94 were administered 48 h and 24 h, respectively, before the induction of acute pancreatitis. Twenty-four hours after the induction of acute pancreatitis, the gut barrier dysfunction and the incidence of bacterial translocation (BT) and PMN transmigration were investigated by bacterial, histologic, and biochemical (MPO) analysis. Inhibition of MMP-9 was achieved by depletion of PMNs or inhibition of MMP-activity by a broad-spectrum MMP inhibitor and confirmed by zymography. In addition, reactive oxygen species were evaluated by spin trap assay. RESULTS: The mucosal injury and the infiltration of PMNs into the gut tissue of rats with SAP were significantly increased in comparison with rats treated with anti-rat PMN serum or BB-94. The levels of MMP-9 and reactive oxygen species in the gut of rats with SAP were significantly higher than those of the rats treated with anti-rat PMN serum or BB-94. Pretreatment with anti-rat PMN serum or BB-94 reduced the incidence of BT in SAP. CONCLUSION: The incidence of BT in SAP was prevented by the depletion of PMNs or less pronounced by the injection of the MMP inhibitor BB-94. PMNs play an important pathophysiologic role in the occurrence of BT, and MMP-9 is involved in both BT and PMN transmigration in rat SAP.
Subject(s)
Bacterial Translocation , Ileal Diseases/immunology , Matrix Metalloproteinase 9/metabolism , Neutrophils/enzymology , Pancreatitis, Acute Necrotizing/complications , Animals , Ileal Diseases/enzymology , Ileal Diseases/pathology , Ileal Diseases/prevention & control , Ileum/immunology , Ileum/pathology , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase Inhibitors , Naphthol AS D Esterase , Neutrophil Infiltration , Pancreas/pathology , Pancreatitis, Acute Necrotizing/enzymology , Pancreatitis, Acute Necrotizing/immunology , Pancreatitis, Acute Necrotizing/pathology , Peroxidase/analysis , Phenylalanine/analogs & derivatives , Phenylalanine/therapeutic use , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Taurocholic Acid , Thiophenes/therapeutic useABSTRACT
BACKGROUND: The overall long-term results of medical treatment for morbid obesity are poor. Surgery is the only treatment option to obtain long-term weight reduction. Analysis of risk factors for treatment success of laparoscopically placed gastric banding (LGB) has not been available until now. METHODS: Prospective study with 99 patients with LGB between January 1997 and July 2003. The parameters assessed as risk factors included onset of obesity, feeling of postprandial satiety, and initial body mass index (BMI). RESULTS: Median follow-up was 36 months (3 to 72). Independent prognostic factors of excess body weight reduction (>25%) were for the first postoperative year: onset of obesity as an adolescent (relative risk [RR] 0.21), an initial BMI <45 kg/m(2) (RR 4.76), and a BMI between 45.1 and 50 kg/m(2) (RR 3.23). After the second year, independent prognostic factors were as follows: feeling of postprandial satiety (RR 5.26) and an initial BMI <45 kg/m(2) (RR 3.03). CONCLUSION: LGB is suitable to achieve intermediate weight reduction in patients with morbid obesity. To obtain the best results, patients should be treated before they achieve a BMI >45 kg/m(2). Additionally a postprandial feeling of satiety after LGB is mandatory for good long-term results.
