Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was confirmed that esterolytic activity was significantly elevated in plasma of patients with acute pancreatitis, which correlated better with the stage of the disease than serum amylase level. Using the several column chromatography procedures, pancreatic kallikrein, trypsin and pancreatic elastase were separated and purified from alpha 2-macroglobulin (alpha 2-M) fractions of patients plasma with acute pancreatitis. From this this result, it was confirmed that kallikrein was liberated into the blood stream from the pancreas during attacks of acute pancreatitis and the liberated kallikrein combined with alpha 2-M. Furthermore, the coexistence of trypsin is required for the complex formation of alpha 2-M and pancreatic kallikrein. It was speculated that alpha 2-M might be decomposed by the excessive amount of elastase, and consequently, might release all of its combining enzymes into the blood stream. In the present study, the activation mechanism of fibrinolytic enzyme system in plasma by human pancreatic elastase was investigated. Elastase not only converted the co-existing plasminogen to low molecular weight plasminogen which could be easily activated by the activators, but also inhibited alpha 2-M and alpha 2-plasmin inhibitor, and consequently, induced the activation of the fibrinolytic enzyme system in plasma. Furthermore, it was also confirmed that elastase could activate plasma kallikreinogen to kallikrein.
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PMID:[Interaction of proteases and their inhibitors in the pathogenesis of pancreatitis]. 241 45

A rat model of taurocholate-induced acute pancreatitis has been employed to investigate the effect of heparin on the protease-antiprotease balance. Heparin was applied intraperitoneally at a dose of 6 mg/kg body weight during 24 hrs. At 24 and 48 hours of acute pancreatitis, heparin evidently diminished the consumption of trypsinogen in pancreatic tissue and decreased trypsin generation. The use of heparin prevented the consumption of alpha 1 anti-chymotrypsin, alpha 1-anti-trypsin and AT-III in pancreatic tissue, whereas in plasma the concentration of the mentioned inhibitors was restored or even increased. Heparin does not affect evidently lowered alpha 2-macroglobulin concentration, either in pancreatic tissue or in plasma. We conclude that heparin applied in acute pancreatitis markedly moderates the dysfunction of protease-antiprotease balance both in plasma and in pancreatic tissue.
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PMID:Does heparin modify protease-antiprotease balance in acute experimental pancreatitis in rats. 242 15

Effects of FUT-175 on the pancreatic enzymes in vitro and in vivo in the enterokinase-induced experimental acute pancreatitis were investigated, and they were compared with those of gabexate and aprotinin. In in vitro experiments, FUT-175 inhibited the pancreatic protease activities 10 to 100 times more potently than gabexate. Furthermore, FUT-175 inhibited the enterokinase activity. Unlike aprotinin, FUT-175 inhibited alpha 2-macroglobulin bound trypsin activity as well as free trypsin. In in vivo experiments, at doses of 0.5-50 micrograms/kg/min, FUT-175 suppressed the elevated protease activities in the experimental acute pancreatitis more potently than gabexate. Differently from the action of aprotinin, FUT-175 suppressed trypsin activities both in the pancreas and in the plasma to the same extent. Furthermore, FUT-175 reduced the mortality of rats in the experimental acute pancreatitis in a dose-dependent manner. These data strongly support that FUT-175 is clinically useful in the therapy of acute pancreatitis.
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PMID:Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats. 242 60

The effects of the cholecystokinin (CCK)-receptor antagonist proglumide, the protease inhibitor gabexate, and the hormones secretin and cholecystokinin-octapeptide (CCK-8) were studied in a model of acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented (CDE) diet. Injections of gabexate and proglumide from initiation of CDE diet (before induction of pancreatitis) increased survival from 37% (diet alone) to 85 and 75%, respectively, and also ameliorated histological alterations and increases in serum amylase concentration and pancreatic activated trypsin. Secretin had no major beneficial effect. When proglumide or gabexate were given after induction of pancreatitis, proglumide still increased survival to 75%, whereas gabexate no longer did. Injection of nontoxic doses of CCK-8 before proglumide or gabexate injections completely abolished all beneficial effects and also increased the severity of pancreatitis due to CDE diet alone. Blockade of CCK receptors and early inhibition of protease activity may be beneficial in severe acute pancreatitis. Cholecystokinin appears to play a contributory role in the development of pancreatitis.
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PMID:Beneficial effects of cholecystokinin-receptor blockade and inhibition of proteolytic enzyme activity in experimental acute hemorrhagic pancreatitis in mice. Evidence for cholecystokinin as a major factor in the development of acute pancreatitis. 242 40

Acute pancreatitis was induced in pigs by retrograde injection of Na-taurocholate into the pancreatic duct. Chromogenic peptide substrate assays showed increased trypsin (TRY) and plasma kallikrein activity (KK), parallel with a reduction of plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) values, in the peritoneal exudate in untreated animals. Intravenous high-dose pretreatment or therapy with aprotinin starting 3 h after the induction of acute pancreatitis resulted in significantly increased KKI capacity and unchanged KK and TRY activities in the peritoneal exudate. In test animals receiving aprotinin intravenously a significantly increased survival rate and improved cardiac output and arterial blood pressure were found during the 6-h observation period. All animals treated with aprotinin survived the observation period, whereas 63% of the untreated animals died. The study emphasizes the pathophysiological importance of the plasma kallikrein-kinin system in acute pancreatitis.
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PMID:Effects on peritoneal proteolysis and hemodynamics of prophylactic and therapeutic infusions of high doses of aprotinin in experimental acute pancreatitis. 243 Mar 29

Acute pancreatitis was induced in pigs by manual retrograde injection of Na-taurocholate into the pancreatic duct. Chromogenic peptide substrate assays showed increased trypsin (TRY) and plasma kallikrein activities (KK), parallel with a reduction of prekallikrein (PKK) levels and functional plasma kallikrein inhibition (KKI), in the peritoneal exudate in untreated animals. Pretreatment with C1 inhibitor (C1 INH) concentrate significantly increased the KKI capacity, parallel with unchanged KK and TRY activities in the peritoneal exudate. Furthermore, C1 INH pretreatment significantly improved the hemodynamic performance and the survival rate during a 6-h observation period. The study underlines the pathophysiological importance of trypsin and the plasma kallikrein-kinin system during acute pancreatitis. C1 INH concentrates given intravenously prevent activation of this system locally in the peritoneal exudate during experimental acute pancreatitis.
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PMID:Effects on peritoneal proteolysis and hemodynamics of prophylactic infusion with C1 inhibitor in experimental acute pancreatitis. 243 Mar 30

To investigate the correlation between the initial levels of serum pancreatic enzymes and the severity of acute pancreatitis, serum amylase activity, immunoreactive trypsin content, phospholipase A2 activity and immunoreactive pancreatic phospholipase A2 content were comparatively measured in 22 patients with acute pancreatitis. Serum immunoreactive pancreatic phospholipase A2 content and phospholipase A2 activity in the severe group were significantly elevated as compared with those in the group of moderate pancreatitis on the first day of onset. The elevation of the initial immunoreactive phospholipase A2 content in the severe group was far greater than that of amylase activity, trypsin content and phospholipase A2 activity. The difference between immunoreactive phospholipase A2 content and phospholipase A2 activity was, in part, due to the presence of prophospholipase A2 in severe acute pancreatitis sera, but the phospholipase A2 content measured by radioimmunoassay was still about 5 times higher than that calculated from fully activated phospholipase A2 activity by trypsin.
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PMID:Usefulness of determination of serum immunoreactive pancreatic phospholipase A2 content for early identification of severe acute pancreatitis. 243

Acute pancreatitis was induced in pigs by manual retrograde injection of Na-Taurocholate into the pancreatic duct. Using chromogenic peptide substrate assays, increased plasma kallikrein activity (KK), paralleled by a reduction in functional plasma kallikrein inhibition values (KKI) were found in the peritoneal exudate in untreated animals. Several of the untreated animals experienced an increased trypsin activity (TRY) in the same exudate. Five out of eight animals died during a 6 hour observation period. Pretreatment with either Cl-INH or aprotinin given intravenously, resulted in a significantly increase in KKI capacity paralleled by unchanged KK and TRY activities in the peritoneal exudate. Furthermore, inhibitor pretreatment significantly improved hemodynamic performances (AP and CO) and the survival rate. The study underlines the pathophysiological importance of trypsin and the plasma kallikrein-kinin system during acute, severe pancreatitis.
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PMID:Effects of protease inhibitor pretreatment on hemodynamic performances and survival rate in experimental, acute pancreatitis. 243 16

The changes in the protease inhibitors and in the kallikrein-kinin system were analysed in 19 attacks of acute pancreatitis in man and correlated to the severity and clinical course of the disease. Functional alpha 2-macroglobulin was 5% in peritoneal fluid and 32% in blood in severe attacks. Functional Cl inactivator was zero in the peritoneal fluid, while values were normal in blood. High levels of complexes between alpha 1-proteinase inhibitor and trypsin were found during the first 6 days of illness in severe attacks, especially in the peritoneal fluid. Prekallikrein, kininogen and kallikrein inhibition were significantly lower in blood in severe attacks than in moderate or mild attacks. These changes were even more pronounced in the peritoneal fluid, where kallikrein-like activity was above normal, while kininogen and kallikrein inhibition were zero in severe attacks. Both high and low molecular weight kininogen were decreased, denoting an activation also by kininogenases other than plasma kallikrein. In conclusion, kinin activation was demonstrated in acute pancreatitis, especially in the peritoneal fluid. Kinin activation and protease inhibitory activity were closely correlated to the severity and clinical course of the disease. Tryptic activation of the kinin system seems probable at the low alpha 2-macroglobulin levels found in severe attacks, according to our earlier in vitro studies.
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PMID:Kinin activation and protease inhibitors in acute pancreatitis in man. 243 17

Cleavage of C3 and kininogen in human plasma following the addition of increasing amounts of human cationic trypsin was studied using an in vitro model. The cleavage was correlated to the degree of saturation of the plasma protease inhibitors alpha 2-macroglobulin and alpha 1-proteinase inhibitor, and also with varying amounts of human pancreatic secretory trypsin inhibitor. When alpha 2-macroglobulin reached about 70% saturation, there was a prompt cleavage of most of the C3 and kininogen in spite of the presence of 90% free alpha 1-proteinase inhibitor. The consumption of alpha 1-proteinase inhibitor decreased with increasing concentrations of the pancreatic secretory trypsin inhibitor. This inhibitor was needed in a concentration of about 10 mumol to block trypsin-induced C3 and kininogen cleavage completely. As trypsin is thought to be the key trigger enzyme of the pathophysiological changes in acute pancreatitis, it seems reasonable to propose that the pancreatic secretory trypsin inhibitor might be of therapeutic interest in severe acute pancreatitis provided large enough amounts can be made available.
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PMID:Influence of the human pancreatic secretory trypsin inhibitor on trypsin-induced C3 and kininogen cleavage: an in vitro study. 243 81


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