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)

Unconscious rats given intravenous ceruletide (diethylamine salt of the decapeptide caerulein) in large pharmacologic doses consistently developed moderate acute pancreatitis by 3 h and florid pancreatitis by 6 h. Biochemical serum markers of acute pancreatitis tended to parallel the severity of the pancreatic damage. In 50% of the rats, mesenteric fat necrosis was present, free peritoneal fluid containing massive elevations of trypsinogen and amylase were noted in most animals. Intravenous secretion at a low dose given simultaneously with ceruletide exerted a variable protective effect on the pathological process. A high dose of secretin produced a striking macroscopic, microscopic, and biochemical protective effect on ceruletide-induced pancreatitis. High resolution light microscopy and electron microscopy showed a marked cellular disorganization in the acini of animals treated with ceruletide alone. By contrast, there was a striking apical redirection of zymogen granules in acini of the animals treated with secretin. The results of this study suggest that high dose intravenous secretin may exert a beneficial effect on acute pancreatitis.
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PMID:Protective effects of exogenous secretin on ceruletide-induced acute pancreatitis in the rat. 619 40

A new radioimmunoassay to serum trypsinogen (Cis Trypsik) was tested in several patient populations. A low serum trypsinogen level (less than 10 ng/ml) was found in 69.2% of 13 patients with chronic pancreatic insufficiency (CPI), in 100% of 10 patients with 95-100% pancreatectomy but only in 14% of 14 patients with cancer of the pancreas. A low trypsinogen level was not found in any of 68 control subjects or 10 patients with nonpancreatic steatorrhea. Nine patients with CPI or 95% pancreatectomy were retested a mean of six months after initial testing. Four of these nine (44.4%) had a significant variation in serum trypsinogen which would have led to a different diagnostic interpretation (two went from low to normal levels and two from normal to low levels). A mixed meal had little effect on serum trypsinogen levels in five of six patients with CPI, and pancreatic enzyme replacement therapy had no consistent effect on the serum trypsinogen level in seven patients with CPI or 95% pancreatectomy. It is speculated that minor subclinical episodes of focal pancreatitis may effect the serum trypsinogen level. Although there can be considerable variability using this assay, it still offers important clinical utility. A low trypsinogen level points to a chronic pancreatic process with excellent specificity. A normal trypsinogen level is of no help and should be repeated if clinical suspicion of chronic pancreatitis remains high.
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PMID:Serum trypsinogen in diagnosis of chronic pancreatitis. 648 92

Majority of literature data support the significance of proteases activation in pathogenesis of acute pancreatitis. The ability of cathepsins to the activation of trypsinogen was shown and the labilization of lysosomes of pancreas in different models of acute experimental pancreatitis (AEP) was reported. In present work the dynamic of lysosomal changes during the course of AEP in dogs is evaluated. AEP was induced in 17 mongrel dogs by Elliot's method. Six healthy dogs served as a control group (I). Pancreatitic dogs were killed after 6 hr (G. II, n = 5), after 12 hrs (G. III, n = 5), and after 24 hrs (G. IV, n = 6 survivors). The pancreata were removed and divided into segments A (less advanced changes, [B] most advanced changes) and C (intermediate changes). The lysosomal enriched subfraction was isolated from the C segments at 15 000 X g for 20 min. The total (T) and free (F) activity of beta-glucuronidase (beta-G), acid phosphatase (AP), acid cathepsins (Cs) was estimated and the value F/T (relative free activity-r.f.a.) was calculated as an index of lysosomal stability. The progressive increase of r.f.a. of hydrolases in whole homogenate and in lysosomal enriched subfraction depending on time of AEP was observed suggesting labilization of pancreatic lysosomes. This labilization was more expressed in corresponding parts of organ with more advanced pathological changes. The differences between part A and B were most evident after 6 hrs of AEP. The labilization of lysosomes is more pronounced after 12 and 24 hrs than after 6 hrs in analogical parts of organ. These results indicate that labilization of lysosomes in pancreas correspond to the degree of pathological changes of pancreatic tissue.
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PMID:Pancreatic lysosomal hydrolases in acute experimental pancreatitis in dogs. 651 6

Experiments on rats have demonstrated that changes in the serotonin level in the body intensifies pancreatic function. The pancreas shows the increased contents of trypsinogen and proelastase and those of lysosomal enzymes (cathepsins and acid phosphatase). Administration of serotonin leads to the reduction of the inhibitory properties of blood serum versus proteolytic pancreatic enzymes. Administration of serotonin to animals with the preliminarily ligated pancreatic duct results in the development of pancreatitis with a pronounced fat necrosis of the pancreatic tissue.
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PMID:[Effect of serotonin on secretory and lysosomal enzyme activity in pancreatic tissue and the inhibitory properties of serum]. 691 1

To determine the role alcohol might play in altering pancreatic function, we have examined pure pancreatic juice, obtained by endoscopic cannulation of the pancreatic duct, from a group of 10 chronic alcoholic subjects without history or clinical or laboratory evidence of pancreatic disease and compared the results with those obtained from 15 healthy, non-alcoholic subjects. These findings confirm observations in experimental animals made by others and support the hypothesis that chronic alcohol abuse may damage the pancreas via a sequence of events involving protein hypersecretion. Increase in concentration was not uniform for all proteins measured. Unexpectedly, chronic alcoholics exhibited a highly significant elevation (two- to three-fold over normal) in trypsinogen, in contrast to statistically insignificant increases of other zymogens and trypsin inhibitor. The strikingly increased ratio of trypsinogen to trypsin inhibitor observed in all our alcoholic patients may indicate a weakening of the defence mechanism provided by the trypsin inhibitor against premature intraductal activation of zymogens and explain the predisposition of these patients to pancreatitis.
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PMID:Studies of pure pancreatic secretions in chronic alcoholic subjects without pancreatic insufficiency. 738 47

Diagnosis of acute pancreatitis (AP) can be obtained with a high level of accuracy by clinical assessment and determination of common laboratory parameters such as serum amylase and lipase concentrations. However, the key of an optimal management of patients with AP is based on an early discrimination between interstitial oedematous and necrotizing forms. The former resolves spontaneously whereas parenchymal necrosis acting as a focus for bacteria has a very high severity. In this respect, multifactor prognostic scoring systems and new biological assessments like C reactive protein are valuable methods for forecasting the prognosis of AP. However, these indicators of severity require a full 48 hour period of observation. In order to overcome these drawbacks, other prognostic criteria have been explored based mainly, on laboratory data. The most interesting ones are trypsinogen activation peptides and leucocyte elastase. Finally, the more useful tool is computed tomography (CT). Combined with high dose intravenous contrast agent, it allows an early identification of necrosis. Other goals of computed tomography are an accurate diagnosis of infection by guided needle aspirations and a preoperative recognition of devitalized and infected tissues, which require a careful surgical necrosectomy. A prolonged drainage is always recommended but relative merits of a conventional closed drainage and an open one are controversial. Another therapeutic challenge is gallstone associated to severe pancreatitis. An early stone removal is advocated by some authors but others prefer delayed surgery because of high mortality rates in case of emergency surgery. Delayed surgery until biological parameters of pancreatitis are normalized seems preferable. An early endoscopic sphincterotomy in an attractive alternative method.
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PMID:[Severe acute pancreatitis: diagnostic approaches and therapeutic implications]. 750 23

The possible role of cathepsin B in the pathogenesis of two forms of acute pancreatitis was studied using the cathepsin B inhibitor known as E-64. In an edematous, nonfatal pancreatitis induced by supramaximal doses of cerulein, increases in the serum amylase and lipase levels were less pronounced in rats pretreated with E-64. Other parameters of pancreatic injury were unaffected by inhibition of cathepsin B. In a necrohemorrhagic type of pancreatic injury induced by retrograde infusion of bile salts into the pancreatic duct, E-64 partially attenuated increases in serum levels of amylase and lipase, and in addition, reduced the activation of trypsinogen. However, the high mortality in this model of pancreatitis was not modified.
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PMID:Cathepsin B inhibition in two models of acute pancreatitis. 750 43

A normal serum amylase level is found in up to 32% of patients with acute alcoholic pancreatitis. This underlines the need for more sensitive diagnostic tests in this frequent cause of pancreatitis. Animal and human studies have shown that chronic alcohol consumption leads to important modifications in trypsinogen metabolism. The present work has prospectively analyzed admission serum trypsin activity with a new biochemical test and usual markers such as amylase, lipase, and immunoreactive trypsin in 32 attacks of acute pancreatitis. Seventeen were due to alcohol and 15 to other causes, including 11 with gallstone pancreatitis. High trypsin activity (median: 235 units/liter; range: 165-853) was found in all patients with acute alcoholic pancreatitis even when the amylase level was normal on admission (3/17: 18%). Trypsin activity did not differ between nonalcoholic pancreatitis (N = 15): 84 units/liter (42-98), alcoholic controls (N = 15): 77 units/liter (40-122), and healthy controls (N = 62): 81 units/liter (15-143). The difference was not related to the severity of disease or circulating alpha 2-macroglobulin, alpha 1-protease inhibitor, or immunoreactive trypsinogen levels. Lipase/amylase ratio was less discriminant than trypsin activity between alcoholic and nonalcoholic diseases. We conclude that serum trypsin activity seems specific to acute alcoholic pancreatitis and should be included in new prospective studies assessing biochemical testing of alcohol-related pancreatic diseases.
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PMID:Trypsin activity. A new marker of acute alcoholic pancreatitis. 752 52

To examine the possible secretion of lysosomal enzymes into the pancreatic juice in rats stimulated with pancreatic secretagogues under both physiological and pathological conditions, we investigated the changes in the secretion of cathepsin B, as a lysosomal enzyme, into pancreatic juice with stimulation of 5 different doses (0.1, 0.2, 0.5, 1.0, and 1.5 micrograms/kg.hr) of caerulein. Control rats had only pancreatic duct cannulation. In other rats, the pancreatic duct was obstructed for 3 hours and secretin was infused (0.2 CU/kg.hr). Caerulein stimulated the secretion of cathepsin B into the pancreatic juice in a dose-dependent manner, as in amylase secretion, and caerulein in higher doses (1.0 and 1.5 microgram/kg.hr) inhibited cathepsin B output as it did amylase output. There was a significantly high positive correlation between cathepsin B output and amylase output after stimulation with caerulein. The secretion of several other lysosomal enzymes was also stimulated by caerulein. Blockage of the pancreatic duct for 3 hours caused a significant but moderate rise in serum amylase levels. Redistribution of cathepsin B activity in the pancreatic subcellular fractions was noted with an increase in the amount of cathepsin B recovered from zymogen-rich pellets after 15 min of centrifugation at 1300 x g. These changes after temporary pancreatic duct obstruction are very similar to those previously noted during the early stage of diet-and caerulein-induced experimental pancreatitis and suggest colocalization of lysosomal enzymes and digestive enzymes. In addition, in duct obstructed rats, the secretion of cathepsin B and other lysosomal enzymes stimulated by caerulein was significantly greater than in animals with free-flowing pancreatic juice. These results indicate that lysosomal enzymes are secreted into pancreatic juice after stimulation by gut hormones in the same manner as classical pancreatic digestive enzymes such as amylase. Moreover, lysosomal enzymes which colocalize with zymogen granules in rats with short-term pancreatic duct obstruction are also secreted into pancreatic juice together with digestive enzymes after stimulation with gut hormones. These findings suggest that lysosomal enzymes are present in zymogen granules under normal conditions and that they may play pathophysiological roles in pancreatic juice. They also contribute to an understanding of the pathogenesis of pancreatitis, since cathepsin B can activate trypsinogen.
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PMID:Lysosomal enzyme secretion into pancreatic juice in rats injected with pancreatic secretagogues and augmented secretion after short-term pancreatic duct obstruction. 752 87

Acute necrotizing pancreatitis in opossums after bile and pancreatic duct ligation (BPDL) is a useful experimental corollary of gallstone-induced acute pancreatitis in humans. In experimental and human acute pancreatitis, a loss of segregation of the lysosomal enzyme cathepsin B and the zymogen proenzyme trypsinogen (colocalization) is implicated as the triggering event of disease pathogenesis, as cathepsin B can activate trypsinogen. The object of this study was to quantitate acinar cell necrosis and to study subcellular distribution of cathepsin B in BPDL-induced acute necrotizing pancreatitis in opossums. Bile and pancreatic ducts were ligated separately (no bile reflux) in four opossums while ducts were dissected in four sham controls. Opossums were killed 24 hr after operation. Three equidistant cross-sectional portions of each opossum pancreas were submitted to histologic examination. In blinded fashion, each focus of acinar cell necrosis was photographed and quantitated with digitizing morphometry. Numerical density (foci/cm2) and areal density (x10(3) micron 2/cm2) of focal acinar cell necrosis were determined. Differentially centrifuged pancreatic homogenates were assayed for cathepsin B, the lysosomal marker enzyme N-acetylglucosaminidase, and amylase. Morphometric quantitation of acinar cell necrosis confirmed development of acute necrotizing pancreatitis after 24 hr of BPDL in opossums. However, colocalization was not observed after BPDL, as evidenced by an absence of subcellular shift of cathepsin B activity (and N-acetyl-glucosaminidase activity) from the lysosome-enriched to the zymogen-enriched subcellular fraction. Amylase activity was increased in subcellular fractions after BPDL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ligation-induced acute pancreatitis in opossums: acinar cell necrosis in the absence of colocalization. 753 Mar 9


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