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Query: UMLS:C0001339 (acute pancreatitis)
 10,593 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activation of canine anionic and cationic trypsinogen by enterokinase, trypsin, thrombin, plasmin and extracts from canine granulocytes were studied in vitro. Enterokinase activates both trypsinogens about 1000 times faster than trypsin. The enterokinase-catalyzed activation is not inhibited by the main serum protease inhibitors, alpha-macroglobulin and alpha 1-antitrypsin. alpha-Macroglobulin cannot inhibit the activation of the trypsinogens by trypsin but this reaction is completely inhibited by alpha 1-antitrypsin. The results are discussed in relation to the pathogenesis of acute pancreatitis.
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PMID:Studies on the activation of canine trypsinogens in vitro. 9 42

A simple method for the purification of anionic and cationic trypsinogen and trypsin from human pancreatic juice applying affinity chromatography on aprotinin coupled Sepharose is described together with the N-terminal amino acid sequences for both trypsinogens. In addition, enzyme-linked immunoabsorbent assay (ELISA) methods for the determination of anionic and cationic trypsin-like immunoreactivity (irAT and irCT) are described. Normal serum levels are 21.3 +/- 7.4 micrograms/l and 27.8 +/- 9.0 microgram/l for irAT and irCT respectively and the accuracy of these assays is 6-10%. In our population, the normal ratio between irCT and irAT in serum is 1.36 +/- 0.42. In normal serum trypsin-like immunoreactivity consists solely of trypsinogen. In acute pancreatitis there is an increase over normal of both irAT and irCT with a proportionally greater increase in irAT than irCT. Similar changes are also found in uremic patients.
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PMID:Immunoreactive anionic and cationic trypsin in human serum. 259 66

The levels of pancreatic digestive enzymes, lysosomal hydrolases, and protease inhibitors were evaluated in ascites fluid from 24 patients with acute pancreatitis diagnosed as alcoholic, gallstone-induced, or idiopathic. In this group the concentrations of amylase (354 +/- 98 ng/ml), immunoreactive cationic trypsinogen (1840 +/- 238 ng/ml), and immunoreactive elastase 2 (1492 +/- 262 ng/ml) were greatly elevated in comparison to the corresponding serum values. Enzyme levels in ascites from the idiopathic pancreatitis group tended to be higher than the levels from the other two groups. Activity of acid phosphatase and beta-glucuronidase was significantly higher in ascites compared to serum in all groups. On the other hand, levels of immunoreactive alpha 1-protease inhibitor and alpha 2-macroglobulin in ascites fluid were about half the average concentrations reported for normal serum. Significant amounts of tryptic amidase activity (61.7 +/- 13.7 micrograms/ml) were observed, indicating a trypsin-alpha 2-macroglobulin complex. These data indicate an imbalance in the protease-to-inhibitor ratio in ascites fluid from patients with acute pancreatitis. Coupled with elevated ribonuclease activity (27.4 +/- 3.4 units), a positive methemalbumin test in 23 of 24 patients (1.1 +/- 0.4 mg hematin/100 ml), and an average protein concentration of 4.0 +/- 0.2 g/100 ml, these observations demonstrate that abdominal paracentesis and the biochemical analyses of ascites fluid provide useful information related to the biochemical events in acute pancreatitis and may be useful in the diagnosis of difficult cases, but their predictive value of severity remains to be established.
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PMID:Biochemical studies in peritoneal fluid from patients with acute pancreatitis. Relationship to etiology. 381 84

In six pigs intravenous administration of Escherichia coli endotoxin caused septic shock and a significant increase in serum cationic trypsin-like immunoreactivity (CTLI), with activation of cationic trypsinogen to trypsin and formation of complexes between cationic trypsin, on the one hand, and alpha 2-macroglobulin and alpha 1-antitrypsin, on the other, compatible with acute pancreatitis. In contrast, intraduodenal infusion of E. coli endotoxin to seven other pigs was without effect on the general circulation and on the serum CTLI.
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PMID:Effect of intravenous and intraduodenal administration of Escherichia coli endotoxin on the porcine pancreas as evaluated by changes in the serum cationic trypsin-like immunoreactivity. 389 Jan 37

The theory of pancreatic gland autodigestion by pancreatic enzymes assumed by Chiari 1886 as the crucial moment in the pathogenesis of acute pancreatitis (AP) remains accepted so far. The appearance of mutations of cationic trypsinogen gene on the 7th chromosome in several families with hereditary AP, supports the significance of trypsin in the initiation of AP. The generally recognized etiologic factors of AP include the biliary tract disease and alcohol. Opie in his "Common Channel theory" assumed that the impacted gallstone in the ampulla of Vater could cause a permanent obstruction and subsequently AP. Later clinical studies have confirmed that a short-term block of the common pancreatic duct caused by migrating gallstones is associated with onset of AP. Chronic consumption of alcohol evokes subclinical pancreatic disturbances already prior to the onset of AP. PAP (pancreatic associated protein) being the marker of pancreatic inflammation was significantly increased in chronic alcoholism without signs of AP. Many pathophysiological concepts and effective therapeutic procedures which were successful in the animal studies have not turned out to be appropriate in man. The destruction of both cellular structure and cellular connections is an early event in the development of experimental AP. There is much evidence that free oxygen radicals and the disturbances of microcirculation determine the severeness of AP. The roles of NO (nitric oxide) and kinins remain to be clarified cytokins a interleukin 2 (IL2) and interleukin 10 (IL10) had a protective effect in experimental AP. In humans the antagonist of PAF (platelet activating factor) had reduced the occurrence of organ failure. There is hope, that this knowledge, will lead to new therapeutic possibilities.
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PMID:[Etiology and pathogenesis of acute pancreatitis]. 972 65

The pancreatic acinar cell is potentially the initial site of injury that begins the series of events leading to acute pancreatitis. Pathological intrapancreatic zymogen activation occurs in experimental pancreatitis in animals and in human pancreatitis. Intracellular activation has been clearly linked to aberrant zymogen processing in one form of hereditary pancreatitis; in this genetic disease a mutation in cationic trypsinogen may eliminate the degradation of any trypsin activated in the acinar cell. Recent studies have also provided the first direct evidence that trypsinogen activation takes place early in the course of caerulein-induced pancreatitis; parallel studies have used isolated pancreatic acini and conditions that simulate those that cause pancreatitis in vivo to demonstrate that zymogens can be pathologically activated in isolated cells. A unique acinar cell pathway regulates the intracellular proteinase processing of zymogens to their active forms. Stimulating the acinar cell with supramaximal concentrations of cholecystokinin (CCK) or carbamylcholine can activate this pathway. The activation depends on a low pH compartment within the acinar cell and activation of an intracellular serine protease. A marker of trypsinogen processing, the trypsinogen activation peptide (TAP), is generated in acinar cell compartments that do not overlap with secretory granules. This compartment overlaps with a marker of recycling endosomes and lysosomes. Thus, zymogen processing within the acinar cell proceeds in a distinct subcellular compartment and is dependent on a low pH environment and activation of serine proteases.
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PMID:Mechanisms of intracellular zymogen activation. 1103 Jun 3

Hereditary pancreatitis is an unusual form of acute and chronic pancreatitis with a familial predisposition. Recently, the gene mutations causing most cases of hereditary pancreatitis have been identified in the cationic trypsinogen gene. The known mutations are trypsinogen R117H and N211. These may predispose to acute pancreatitis by eliminating one of the fail-safe mechanisms used by the pancreas to eliminate prematurely activated trypsin. Accumulation of active trypsin mutants are hypothesized to initiate a digestive enzyme activation cascade in the pancreatic acinar cells leading to autodigestion, an intense inflammatory response, and acute pancreatitis. The observation that these patients also develop typical chronic pancreatitis and may later develop pancreatic cancer provides strong evidence that these conditions are linked. Knowledge of the pathophysiological conditions leading to acute and chronic pancreatitis and the development of a transgenic mouse expressing the mutant human trypsinogen genes will provide directions and tools necessary for the effective treatment or prevention of this human disease.
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PMID:Hereditary pancreatitis: new insights, new directions. 1103 Jun 5

Three-point mutations (R117H, N211, A16V) within the cationic trypsinogen gene have been identified in patients with hereditary pancreatitis (HP). A genetic background has also been discussed for idiopathic juvenile chronic pancreatitis (IJCP), which closely mimicks the clinical pattern of HP, and alcoholic chronic pancreatitis because only a small number of heavy drinkers develop pancreatitis. This prompted us to screen 104 patients in our well-defined pancreatitis cohort for the currently known cationic trypsinogen gene mutations. The R117H mutation was detected in seven patients (six patients of two clinically classified HP families, one patient with clinically classified IJCP) and the A16V mutation in one IJCP patient. No cationic trypsinogen gene mutations were found in the remaining 96 patients with chronic and recurrent acute pancreatitis of various etiologies. Our results demonstrate the need for genetic testing to exclude HP, particularly in the presence of an atypical or unknown family history. In addition, cationic trypsinogen gene mutations are no predisposing factor in patients with chronic and recurrent acute pancreatitis of different etiologies.
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PMID:Trypsinogen gene mutations in patients with chronic or recurrent acute pancreatitis. 1113 65

Hereditary pancreatitis is an autosomal dominant form of chronic pancreatitis. It presents with recurrent attacks of acute pancreatitis, usually starting in early childhood. The attacks may vary from mild abdominal pain to pancreatic necrosis, splenic vein thrombosis, pseudocysts and death. Ultimately chronic pancreatitis ensues with unrelenting pain, calcifications, endocrine and exocrine dysfunction. The penetrance is estimated at 80%. With the use of genetic linkage analysis the gene for hereditary pancreatitis was placed on the long arm of chromosome 7 (7q35). Mutational analysis identified cationic trypsinogen as the disease gene. Cationic trypsinogen mutations are thought to result in resistance of this molecule to autolysis.
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PMID:[From gene to disease; hereditary pancreatitis]. 1114 96

Progress in understanding pancreatic diseases has been limited by a number of factors. Primary problems include the absence of good animal models, and difficulty in understanding the origin of pancreatic disease since the disease is usually manifest by the progressive destruction of the gland itself. Beginning in 1995, our laboratory, with the support of the Midwest Multicenter Pancreatic Study Group, began investigating the genetic basis of hereditary pancreatitis. Utilization of information becoming available through the human genome project allowed us to map and identify the hereditary pancreatitis gene as cationic trypsinogen (PRSS1). Molecular modeling, and subsequent experimental evidence, has solved key elements of the mysteries surrounding the origin of acute pancreatitis and the progression of acute pancreatitis to chronic pancreatitis. The availability of new genetic information and genomic tools should produce a revolution in our understanding of pancreatic diseases.
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PMID:Hereditary pancreatitis: a model for understanding the genetic basis of acute and chronic pancreatitis. 1212 Feb 37


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