Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that leucocytes play an important role in the pathogenesis of complicated pancreatitis. Indeed, increased plasma concentrations of neutrophil elastase as a marker of neutrophil activation could be detected in patients with a severe course of the disease. Recently, interleukin-8 (IL-8) has been described as a novel neutrophil activating peptide. To determine the role of IL-8 in acute pancreatitis we measured its serum concentrations by a specific enzyme-linked immunosorbent assay in 10 patients with acute pancreatitis daily during the first week of hospitalization. IL-8 levels were compared with plasma concentrations of neutrophil elastase and the clinical course of the disease. Three of the patients had uncomplicated pancreatitis, while seven showed various extrapancreatic complications. Patients with complicated pancreatitis had statistically significant (P less than 0.05) higher mean values of IL-8 (121 +/- 41 pg/ml-1 vs. 13 +/- 6 pg ml-1, mean +/- SEM) and neutrophil elastase (547 +/- 35 ng ml-1 vs. 250 +/- 20 ng ml-1) than patients with uncomplicated disease. There was a positive correlation (r = 0.52, P less than 0.0001) between IL-8 and neutrophil elastase in the lower concentration range of IL-8 (less than 100 pg ml-1). At IL-8 levels greater than 100 pg ml-1 neutrophil elastase was always greatly elevated; however, under these conditions the relationship between IL-8 and elastase was no longer linear. No measurable IL-8 concentrations were found when plasma elastase was less than 200 ng ml-1. During follow-up, initially elevated IL-8 concentrations decreased in correlation with clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-8 and neutrophil activation in acute pancreatitis. 158 45

Complexes of granulocyte elastase and alpha 1-antitrypsin are markers for granulocyte activation. In 75 patients with acute pancreatitis these complexes were immunologically determined daily in plasma during the first week of hospitalization. Patients were classified into three groups: mild pancreatitis (I, less than or equal to 1 complication, N = 34), severe pancreatitis (II, greater than or equal to 2 complications, N = 29), lethal outcome (III, N = 12). Initially, granulocyte elastase (mean +/- SEM) was lower in group I (348 +/- 39 micrograms/liter) as compared to groups II (897 +/- 183 micrograms/l) and III (799 +/- 244 micrograms/liter), P less than 0.001 for I vs II + III. Initial elastase concentrations greater than 400 micrograms/liter were consistent with a severe or fatal course of the disease but did not distinguish between severe and lethal pancreatitis. In patients with mild or severe disease, mean elastase concentrations decreased continuously during the following days (197 +/- 15 micrograms/liter in mild cases, 325 +/- 30 micrograms/liter in severe cases at day 7). In patients with lethal disease, however, mean elastase concentrations even increased at day 2 and remained higher than 700 micrograms/liter during the observation period. At days 1 and 2 the predictive value for severe or lethal disease of raised (greater than 400 micrograms/liter) elastase concentrations [positive predictive value (PPV) 82%, negative predictive value (NPV) 81%] was better than that of elevated (greater than 100 mg/liter) C-reactive protein (PPV 73%, NPV 73%), elevated (greater than 4.0 g/liter) alpha 1-antitrypsin (PPV 59%, NPV 50%), or decreased (less than 1.5 g/liter) alpha 2-macroglobulin (PPV 82%, NPV 67%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte elastase in assessment of severity of acute pancreatitis. Comparison with acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and protease inhibitor alpha 2-macroglobulin. 168 26

A specific ELISA has been developed for the determination of alpha 1-proteinase inhibitor-bound leukocyte elastase in canine plasma and tissue fluids. Comparison of the sequence of the first 16 N-terminal amino acids of the isolated canine leukocyte elastase to other elastases indicated moderate homology with porcine pancreatic elastase and pronounced identity with human leukocyte elastase. Normal canine plasma contains about 66 micrograms/l leukocyte elastase measured as elastase alpha 1-proteinases inhibitor complexes. This represents about 70% of the total amount of leukocyte elastase released in plasma. The remaining 30% is bound by alpha 1 alpha 2-macroglobulin. Blood coagulation leads to a rapid release of elastase from the leukocytes. Slow intravenous infusion of a lethal dose of endotoxin into dogs is followed by a marked drop in leukocyte count and a simultaneous rapid increase in plasma leukocyte elastase concentration reaching a plateau level of 2-3 mg/l plasma. Bile-induced pancreatitis in dogs is accompanied by successive increases in leukocyte elastase levels in plasma as well as in peritoneal exudates, reaching a level of about 15 mg/l in the exudates during the late stages of disease.
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PMID:Release of immunoreactive canine leukocyte elastase normally and in endotoxin and pancreatitic shock. 169 Apr 43

Complexes of alpha 1-proteinase inhibitor and leukocyte elastase could be demonstrated by crossed immunoelectrophoresis of the peritoneal fluid from four patients who developed a pancreatic abscess during an attack of pancreatitis. No such complexes were seen in 69 patients with acute pancreatitis without an abscess. The complexes were demonstrable 2-3 days before the abscess was clinically evident. They may thus be diagnostically and therapeutically important. The appearance of these complexes denotes the liberation of large amounts of leukocyte elastase. This may help explain the pathophysiology and high mortality of the pancreatic abscess, since leukocyte elastase is known to cause degradation of all components of connective tissue and also degradation and activation of many components within the different cascade systems.
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PMID:Leukocyte elastase alpha 1-proteinase inhibitor complexes may diagnose pancreatic abscesses early. 348 7

Proteases have a wide range of functions: digestion (pancreatic proteases), protein catabolism (lysosomal proteases), blood coagulation, immune defences (complement), cellular division and proliferation, generation of biologically active oligopeptides (kinins, hormones) from inactive polypeptide precursors, inactivation of these oligopeptides, etc. The body protects itself against its own proteases, either by confining them to a given compartment (lysosome), by synthesising them in the form of inactive precursors (trypsinogen, prothrombin, etc.), or by synthesising proteins with an antiprotease activity. Any disturbance in one of the elements of this protective system may lead to severe pathological consequences: acute hemorrhagic pancreatitis with shock, coagulation disturbances (deficient hepatic synthesis of coagulation factors, congenital antithrombin III deficiency), angioneurotic oedema (congenital deficiency of C'l esterase inhibitor) pulmonary emphysema (local secretion of leukocyte elastase, congenital deficiency of alpha a-antitrypsin).
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PMID:[Problems in intensive care posed by imbalance in the protease--protease inhibitor system]. 611 Dec 72

The protective effects of a neutrophil elastase inhibitor (ONO-5046) on cerulein-induced pancreatitis followed by a septic challenge with intraperitoneal lipopolysaccharide (LPS) were studied in a rat model. Pancreatitis was induced by four intramuscular injections of cerulein (50 micrograms/kg at 1-hr intervals). ONO-5046 was administered by continuous intravenous infusion via the right jugular vein (50 mg/kg/hr, 30 min prior to the first cerulein injection to 20 hr following the last cerulein injection). Significant differences in serum amylase and pancreatic wet weight ratio were not observed between the animals with pancreatitis treated with or without ONO-5046. There was no significant difference in the in vitro tumor necrosis factor-alpha (TNF-alpha) production by peritoneal macrophages from rats with pancreatitis treated with or without ONO-5046. In a second experiment, LPS (10 mg/kg) was administered intraperitoneally as the septic challenge 6 hr following the first cerulein injection. Lung hemorrhage was seen in the animals with pancreatitis untreated with ONO-5046 24 hr following the first cerulein injection. No significant lung hemorrhage was observed in the animals with pancreatitis treated with ONO-5046 administering 30 min prior to the first cerulein injection. These results suggest that lung hemorrhage in cerulein-induced pancreatitis that follows a septic challenge with LPS can be prevented by the intravenous administration of ONO-5046. Thus there is a significant role for neutrophil elastase in pancreatitis-associated lung injury.
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PMID:Neutrophil elastase inhibitor (ONO-5046) prevents lung hemorrhage induced by lipopolysaccharide in rat model of cerulein pancreatitis. 758 85

Levels of leukocyte elastase and neutrophil protease 4 (NP4(3)) in plasma and peritoneal exudate were studied in 25 patients with severe, acute pancreatitis. Pancreatitis was diagnosed from the clinical picture and an increased serum amylase level. The diagnosis was verified by computerized tomography, ultrasound, and findings at operation or autopsy. Peritoneal exudate on admission contained high concentrations of leukocyte elastase (6100 +/- 2000 micrograms/l) and NP4(3) (2310 +/- 900 micrograms/l). High initial levels were found also in plasma, which contained 659 +/- 110 micrograms/l of leukocyte elastase and 254 +/- 33 micrograms/l of NP4(3). The levels in plasma were still increased 3 weeks after the acute attack, also in the absence of complications, indicating that the resolution of acute pancreatitis is a protracted process. Plasma levels of both leukocyte proteases were persistently increased in patients with pancreatic abscess, in contrast to the gradual decrease seen in patients with a pseudocyst or uncomplicated recovery. The levels were increased already before the abscess was diagnosed clinically, which indicates that determinations of leukocyte elastase and NP4(3) may be helpful in detecting this complication. A pathophysiologic role for leukocyte proteases in the development of severe, acute pancreatitis should be considered.
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PMID:Levels of leukocyte proteases in plasma and peritoneal exudate in severe, acute pancreatitis. 804 15

Infectious complications are the leading cause of death in acute pancreatitis. Individual factors of immune defence could be of significance, whether or not a patient develops a severe course with infectious complications. In a prospective 5-year trial including 72 patients, we investigated 29 cellular and humoral markers of the body's defence system for their potential to indicate the severity and course of acute pancreatitis. Complement factors C3 and C4 as well as immunoglobulins IgG, IgM and IgA were normal, in general. Measurable levels of IL-1 alpha, IL-1 beta, IL-2 and sIL-2R could be detected only occasionally. Values of alpha 1-AT, TNF-alpha, TNF alpha-Rp75, neopterin, sICAM-1, IL-8, IL-1RA and sIL-6R did not correlate with a severe course. Due to the high magnitude of increase, CRP, IL-6 and granulocyte elastase were the best indicators of the inflammatory process. Delayed-type hypersensitivity response was the only early predictor of a severe course. It was superior over other cellular markers such as monocyte count or CD4+/CD8+ ratio. In vitro function of polymorphonuclear granulocytes (PMN) was not adequate to the severity of the disease already during the first week of illness. During further course, PMN motility and capacities to produce reactive oxygen species even worsened. The compromized PMN function could explain the frequent development of infectious complications in patients suffering from severe pancreatitis. These results should encourage new concepts of infection prophylaxis using stimulants of cellular defence.
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PMID:[Cellular and humoral functions in acute pancreatitis]. 913

A severe acute pancreatitis was produced by intraperitoneal injection of lipopolysaccharide (LPS) in rats with preexisting hemorrhagic and necrotizing pancreatitis induced by retrograde injection of a 5% taurocholate plus 1% trypsin solution into the pancreatic duct. Mortality and time-course changes in pancreatic, hepatic, renal and pulmonary functions, and organ myeloperoxidase (MPO) levels were examined in this model. LPS at an intraperitoneal dose of 30 mg/kg, which scarcely caused death and had no marked effect on serum parameters and organ MPO levels in rats without pancreatitis, increased the mortality in rats with taurocholate plus trypsin-induced pancreatitis. Pancreatic weight and ascitic volume increased in rats with taurocholate plus trypsin-induced pancreatitis regardless of the presence or absence of LPS. Serum amylase and lipase levels were also significantly increased in rats with induced pancreatitis, but was higher in the group given LPS. Serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN) and creatinine levels were significantly elevated in LPS-treated rats with induced pancreatitis, whereas levels in rats with induced pancreatitis not given LPS were only slightly elevated. Renal weight was also significantly increased in rats with induced pancreatitis despite the presence or absence of LPS. In LPS-treated rats with induced pancreatitis, the arterial oxygen pressure, pulmonary weight and pulmonary MPO level were significantly elevated. However, the MPO level in the kidney in these rats was not different from that in control rats, indicating that the renal dysfunction was not produced by the infiltration of neutrophils into the kidney. Increase in the pancreatic MPO level was observed in rats with induced pancreatitis, but combination treatment with LPS did not raise it. Protective effects of prophylactic treatment of 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, and trifluoroacetyl-L-lysyl-L-alaninanilide hydrochloride (compound 2), a pancreatic elastase inhibitor, on mortality were also examined in this model. Results were compared with that of the combined treatment of compound 1 and compound 2. In LPS-treated rats with taurocholate plus trypsin-induced pancreatitis, the combined treatment of compound 1 (2 mg/kg/h) and compound 2 (30 mg/kg/h) significantly reduced mortality, whereas single treatment of compound 1 or compound 2 did not show the beneficial effect. These results suggest that marked hepatic and renal dysfunction accompanies pancreatitis in this pancreatitis model rats, which may be good models for acute pancreatitis in humans. It is also suggested that neutrophil and pancreatic elastases may be synergistically involved in the pathogenesis of acute pancreatitis in this model.
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PMID:Protective effect of the combined treatment of pancreatic and neutrophil elastase inhibitors on acute pancreatitis elicited by lipopolysaccharide in rats given intraductal injection of taurocholate plus trypsin. 965 Aug 10

The inhibitory effects of YM264, a selective platelet activating factor (PAF) receptor antagonist, and 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, on mortality, and pancreatic, hepatic, renal and pulmonary dysfunction were evaluated in a rat model of multiple organ failure (MOF) accompanying acute pancreatitis. MOF was produced by intraperitoneal injection of lipopolysaccharide (LPS, 30 mg/kg) in rats with cerulein-induced pancreatitis. LPS dose-dependently increased the mortality in rats with or without pancreatitis. The threshold dose which produced death in rats without pancreatitis was 30 mg/kg. This same dose evoked death in more than 40% of rats with pancreatitis. Time-course changes in serum enzyme and organ myeloperoxidase (MPO) levels were first examined in rats with induced MOF, and the results were compared with those in rats treated with only LPS or cerulein. Pancreatic weight, and serum amylase and lipase levels significantly increased in rats with cerulein-induced pancreatitis despite the presence or absence of LPS, but recovery of these pancreatic dysfunctions was slower in the group given LPS. However, serum GOT, GPT, BUN and creatinine levels were significantly elevated only in MOF rats. In the MOF rats, the MPO level in the lung was significantly elevated and arterial oxygen pressure was decreased, indicating that infiltration of neutrophils into the lung might be involved in pulmonary dysfunction. However, the MPO levels in the pancreas and kidney in the MOF rats were not remarkably different from those in normal rats. The inhibitory effects of YM264 and compound 1 on mortality and organ dysfunction were examined in this MOF model. The 24-h survival rate for rats prophylactically and therapeutically treated with an intravenous infusion of YM264 at 0.1 mg/kg h was significantly higher than that of controls. The 24-h survival rate for rats treated prophylactically by intravenous infusion of 2 mg/kg h of compound 1 was significantly higher than that of control, whereas a beneficial dose of compound 1 was 5 mg/kg h in therapeutically treated rats. Prophylactic treatment with YM264 (0.1 mg/kg h) and compound 1 (2 mg/kg h) ameliorated organ dysfunction in rats with MOF. In conclusion, pancreatic, hepatic, renal and pulmonary dysfunctions are observed in this rat MOF model. The PAF receptor antagonist and neutrophil elastase inhibitor reduce the mortality rate in rats with MOF due to their inhibitory effects on organ dysfunction, indicating that PAF and neutrophil elastase may play important roles in the development of MOF. These results in the present model are largely consistent with those in patients with MOF, indicating that this model is suited for MOF in humans and may be used as a model to test new therapeutic approaches.
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PMID:Protective effects of a PAF receptor antagonist and a neutrophil elastase inhibitor on multiple organ failure induced by cerulein plus lipopolysaccharide in rats. 975 12


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