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)

The currently available radioimmunoassays of trypsin measure total immunoreactive trypsin (EC 3.1.1.7), which includes both trypsinogen and alpha 1-protease inhibitor-bound trypsin. Hitherto, the only way to differentiate these two forms of trypsin has been to fractionate them on a gel-filtration column. We describe here a solid-phase immunoenzymometric assay that rapidly measures the amount of cationic trypsin bound to alpha 1-protease inhibitor in the plasma of rats with experimental pancreatitis. The assay specifically measures this complex within the range from 0.2 to 5.0 ng without interference by high concentrations of free alpha 1-protease inhibitor. The high correlation (r = 0.985) of the values obtained by size fractionation and by this assay demonstrates the accuracy of the assay, which is the first single-tube method for determining this form of activated cationic trypsin in plasma.
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PMID:Immunoenzymometric determination of trypsin/alpha 1-protease inhibitor complex in plasma of rats with experimental pancreatitis. 352 80

Different materials dissolved in 0.9% NaCl were injected into the connective, interlobular tissue of the duodenal part of the rat pancreas. Activated rat pancreatic juice or trypsin were able to induce localized necrohemorrhagic pancreatitis. Only mild edema and leukocytic infiltration were observed after injecting bovine albumin, chinese ink, trypsinogen or nonactivated pancreatic juice. The progression of histological changes was followed for 2 weeks in the trypsin-induced pancreatitis. Limited foci of severe hemorrhage, liquefaction and coagulative necrosis were observed in the first 24 h. Acinar cell degeneration and regeneration were observed 48 h after the operation, fibroblasts appearing in the interlobular spaces. Four days after injection, inter- and intralobular fibrosis, acinar cell degeneration and tubular complexes were observed, presenting a picture characteristic of chronic pancreatitis. Some minimal changes were still seen in the pancreas 1 week after injection, but by the end of the 2nd week the pancreatic histology was normal. These results demonstrate the significance of active trypsin in the pancreatic interstitium with respect to the induction of pancreatitis. This model of localized necrohemorrhagic pancreatitis is highly reproducible and without significant mortality. Following the acute process, histological changes resembling chronic pancreatitis can be observed, but they are completely reversible.
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PMID:Localized necrohemorrhagic pancreatitis in the rat after pancreatic interstitial trypsin injection. Regressive pseudochronic lesions. 373 40

To study the regulation of the successive steps along the secretory pathway in the rat exocrine pancreas the model of in vivo infusion of synthetic caerulein in conscious rats for periods up to 72 h was combined with electron microscopy and in vitro analysis of protein synthesis, intracellular protein transport and enzyme discharge using isolated pancreatic lobules. Prolonged and maximal hormonal stimulation was obtained with 0.25 microgram kg-1 h-1 caerulein and resulted in a 80-90% depletion of enzyme stores within 1 to 3 h, followed by coordinate and anticoordinate changes in individual rates of (pro-)enzyme synthesis after a lag period of 3 h. One group (two amylases) revealed a decrease in synthesis to levels about 10-fold lower than controls. A third group of proteins (one trypsinogen, lipase, proelastase) did not show changes in synthesis with hormone stimulation. The sum of such alterations led to an increase in total rate of synthesis after 6 h, which was combined with acceleration of intracellular transport, packaging, and granule discharge, thus enabling a sustained rate of secretion over the period of stimulation. In contrast, infusion of a supramaximal dose of caerulein (5.0 micrograms kg-1 h-1) induced acute edematous pancreatitis and led to an almost complete reduction of volume and protein output from the cannulated main pancreatic duct. Using freeze-fracture techniques and thin-section electron microscopy, earliest structural alterations were observed at membranes of zymogen granules and the plasma membrane. Fusion of zymogen granules among each other led to formation of large membrane-bound vacuoles within the cytoplasm. These and individual zymogen granules fused with the lateral instead of the apical plasma membrane, discharging their content into the interstitial space. Vacuole formation was associated with activation of lysosomes and with cytoplasmic destruction of acinar cells. The findings indicated severe changes in the specificity of the intracellular membrane fusion process induced by supramaximal doses of caerulein, which finally resulted in autodigestion of the pancreas.
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PMID:Structural and biochemical characterization of maximal and supramaximal hormonal stimulation of rat exocrine pancreas. 385 14

FOR MANY DECADES TWO TYPES OF ACUTE PANCREATITIS HAVE BEEN RECOGNIZED: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary alpha-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess.
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PMID:Acute pancreatitis. 455 67

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

Prostaglandins have been noted to have a "protective" effect against gastrointestinal mucosal injury induced by a wide variety of agents although possible protective effects of prostaglandins on injury to other tissues have not been reported. We have tested the effect of prostaglandin E2 (PGE2) on acute experimental pancreatitis induced by feeding young female mice a choline-deficient ethionine-supplemented (CDE) diet for 24 hr. Administration of 0.05--0.20 microgram PGE2/g body wt 1 hr before and 4 hr after institution of the CDE diet lowered the mortality rate of diet-induced pancreatitis from 56% to 31%. Larger and smaller doses of PGE2 were without effect. Administration of PGE2 (0.10 microgram/g body weight) diminished the rise in in-vitro LDH discharge and the increase in "free" Cathepsin D activity which occur during diet-induced pancreatitis. Similarly, PGE2 (0.10 microgram/g body wt) diminished the magnitude of the increase in in-vitro protein discharge and the elevated concentrations of trypsinogen and chymotrypsinogen in pancreas fragments taken from mice given the CDE diet. These findings indicate the PGE2 has a protective effect against CDE diet-induced acute experimental pancreatitis. The Cathespin D and LDH changes noted during CDE diet-induced pancreatitis suggest that this diet may decrease membrane integrity and thus allow these enzymes to leak out of the lysosomes and acinar cell, respectively, during pancreatitis. Although the basis for the protective effect of PGE2 remains unclear, our observations suggest that the prostaglandin may act to reduce the alteration in membrane integrity which occurs during CDE-diet induced pancreatitis.
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PMID:Protective effects of PGE2 on diet-induced acute pancreatitis in mice. 615 72

Radioimmunoassays for anionic and cationic dog trypsins are described. Characterization of the immunoreactivities in sera from fasting dogs demonstrated the presence of the two proenzymes only. Fasting sera from 10 dogs contained anionic and cationic trypsinogen in concentrations between 17-110 micrograms/l and 7-19 micrograms/l, respectively. Induction of experimental pancreatitis in dogs was accompanied by a large increase of immunoreactive anionic and cationic trypsins in the circulation. During the progress of the pancreatitis, immunoreactive trypsin with larger molecular weight than trypsinogen appeared. This high molecular weight immunoreactive trypsin was not seen in serum after intravenous injection of pancreatic juice in dogs. The high molecular weight immunoreactive trypsin probably consists of trypsin in complex with protease inhibitors. In vitro studies showed that the immunoreactivity of trypsin decreased considerably after binding to alpha 1-antitrypsin or alpha-macroglobulins.
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PMID:Immunoreactive trypsins in sera from dogs before and after induction of experimental pancreatitis. 615 94

A canine model of bile-induced pancreatitis has been employed to investigate time-dependent changes in the molecular forms of trypsin in blood and ascitic fluid in this disease. The distribution of immunoreactive trypsin as trypsinogen and trypsin bound to plasma inhibitors in ascitic fluid and plasma during the course of the disease has been investigated by means of a radioimmunoassay for canine pancreatic cationic trypsin. In addition, trypsinlike amidase activity was determined in plasma and ascitic fluid using Z-Gly-Gly-Arg-beta-Nap as substrate. Early plasma and ascitic fluid samples in four dogs that died contained primarily trypsinogen, while extensive activation of trypsinogen to alpha 2-macroglobulin and alpha 1-protease inhibitor-bound trypsin occurred in the course of the disease. A fifth dog survived and showed little activation of trypsinogen. In the four dogs that died, the levels of trypsinlike amidase activity in the ascitic fluid were substantial throughout the course of the disease. The plasma levels of trypsinlike activity in these animals were much lower, but increased during the disease process. The dog that survived had lower concentrations of trypsinlike activity in ascitic fluid and plasma. These results suggest that activation of trypsinogen resulting in inhibitor-bound forms of trypsin in ascitic fluid and plasma is important in the pathogenesis of acute pancreatitis.
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PMID:Immunoreactive forms of cationic trypsin in plasma and ascitic fluid of dogs in experimental pancreatitis. 617 Feb 31

The aim of the present study was to determine the effect of prolonged ethanol intake on the morphology and protein metabolism in the rat pancreatic acinar cells. Weight-matched triplets of Sprague-Dawley rats were fed Lieber-DeCarli diet containing 5% (wt/vol) concentration of ethanol, isocaloric amounts of Lieber-DeCarli diet, or rat chow ad libitum for 6, 12, and 18 mo. In the ethanol-fed group, histologic studies by light microscopy showed absence of protein plugs in the pancreatic ducts and/or pancreatitis, but electron-microscopic evaluation revealed progressive accumulation of lipid droplets in acinar and ductal cells. No definite changes in the mitochondria and endoplasmic reticulum were noticed. Biochemical studies revealed increased specific activity of trypsinogen, chymotrypsinogen, and lipase, and decreased specific activity of amylase. Trypsin-inhibiting capacity was decreased in the tissue and in the medium in a progressive fashion. There was no increase in the secretion of total protein. These data show a complex and a nonparallel alteration of specific digestive enzymes and trypsin inhibitor in this model of chronic ethanol intoxication that may be of relevance to occurrence of pancreatitis.
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PMID:Pancreatic acinar cell function and morphology in rats chronically fed an ethanol diet. 617 13

The effect of long-term ethanol intake on pancreatic digestive enzyme secretion was determined in Sprague-Dawley rats. Weight-matched triplets were fed Lieber-DeCarli diet containing 5% w/v concentration of ethanol, isocaloric amounts of Lieber-DeCarli diet, or rat chow ad libitum for 6, 12, and 18 months. Basal and bethanechol-stimulated secretion of amylase, lipase, trypsinogen, chymotrypsinogen, and pancreatic secretory trypsin inhibitor (PSTI) was determined. In the ethanol-fed group, basal secretion of trypsinogen and chymotrypsinogen was increased at 6, 12, and 18 months. In addition, basal secretion of amylase and lipase was increased and that of PSTI was decreased at 12 and 18 months. Secretion of PSTI was stimulated by bethanechol (10(-4)M), whereas the secretion of digestive enzymes was not stimulated in the ethanol-fed versus two control groups. At 12 months the dose-response curve of amylase and lipase secretion was shifted upwards in the ethanol-fed group with increase in ED50. These data are suggestive of membrane perturbations leading to increased basal secretion and a subsensitivity of the cholinergic receptors in the ethanol-fed group. Increased basal secretion of proteases in the presence of diminished trypsin inhibitor indicates that premature activation of proenzymes could occur resulting in pancreatitis.
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PMID:Effect of chronic ethanol feeding on pancreatic enzyme secretion in rats in vitro. 618 44


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