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)

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

Acute pancreatitis was induced in 15 anesthetized pigs by injection of Na-taurocholate into the pancreatic duct. Seven animals were pretreated with methyl-prednisolone sodium succinate 30 mg/kg intravenously. Using chromogenic peptide substrate assays, values of trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and arterial pressure (AP) were regularly monitored before and during a six hour observation period. In acute untreated pancreatitis a 40% reduction of PKK levels was found paralleled by an increased KK activity and a reduction of KKI capacity. High TRY levels were found in several animals. The mortality rate was 63%. The pretreated animals all survived. CO and AP were significantly less reduced than in the untreated animals. Components of the plasma kallikrein-kinin system and TRY in the exudate remained mainly unchanged. Methyl-prednisolone given as pretreatment significantly improves hemodynamic parameters and increases the survival rate. Methyl-prednisolone suppresses generation of trypsin activity and activation of the plasma kallikrein-kinin system in the peritoneal exudate which may be of significant importance to the outcome.
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PMID:Effects on peritoneal proteolysis and hemodynamics by high doses of methyl-prednisolone in experimental acute pancreatitis. 243 82

Various factors in the kallikrein-kinin system were evaluated in acute and chronic pancreatitis. It was noted in particular that plasma trypsin and glandular kallikrein increased markedly in acute phase of pancreatitis and its correlation with amylase was observed. Plasma prekallikrein (PPK) decreased in acute pancreatitis, but increased in chronic pancreatitis. A negative correlation was noted between PPK and kallikrein like activity. Both HMW and LMW kininogen decreased in acute pancreatitis. It was presumed from these findings that the increase in kinin and its activation at the acute phase of pancreatitis might be due to kallikrein or trypsin originating from the pancreas.
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PMID:Role of the kallikrein-kinin system in human pancreatitis. 248 54

Disorders in the blood kallikrein-kinin system presenting mainly with kallikrein elevation and accelerated rate of bradykinin release from kininogen, hyperhistaminemia and hyperserotoninemia may be considered natural for chronic recurrent pancreatitis at the height of its exacerbation. Despite attenuation of the aggravation some patients continue to exhibit the above changes. Upon the analysis of the prospective follow-up data, such patients develop more progressive deficiency of pancreatic enzymes as shown by repeated pancreozymin tests. This fact is under consideration in the discussion on the prognostic role of kallikrein-kinin system dysfunction, hyperhistaminemia and hyperserotoninemia persistent registration when advancing the remission of the disease.
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PMID:[A prognostic criterion for the course of chronic recurrent pancreatitis]. 262 65

After intravenous blood exposure to low-intensity radiation of Helium-Neon laser patients with haemorrhagic pancreatitis exhibited inhibition of the blood proteolytic activity; enhancement of free-radical oxidation, kallikrein-kinin system activity, blood oxygen transport, correction of endotoxic pancreatogenic syndrome. In addition, the positive shifts were also observed in the immunological status, morphofunctional characteristics of the red blood cells and hemoglobin, hepatic and renal functions. In severe pancreatogenic endotoxicosis the highest response was achieved with combined use of hemosorption and intravenous laser irradiation.
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PMID:[Effect of intravenous laser irradiation of blood on the homeostasis in patients with hemorrhagic pancreatitis]. 281 Dec 43

The inhibitory effect of gabexate mesylate, which is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation, and as a regional anticoagulant agent for hemodialysis, has been measured on bovine factor Xa, bovine alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, human urokinase, porcine pancreatic beta-kallikrein-B, and bovine beta-trypsin catalyzed hydrolysis of p-nitrophenyl esters of N-alpha-carbobenzoxy-L-arginine and N-alpha-carbobenzoxy-L-lysine. On the basis of enzyme:gabexate mesylate affinities, the serine proteases can be arranged as follows: human urinary kallikrein approximately porcine pancreatic beta-kallikrein-B much less than bovine beta-trypsin approximately bovine factor Xa approximately human Lys77-plasmin approximately human urokinase approximately bovine alpha-thrombin. The mode of binding of gabexate mesylate to the serine proteases conforms to the active-reactive site geometries observed in their complexes with natural and synthetic inhibitors. Differences in gabexate mesylate affinities for these proteases reflect structural differences at their primary specificity subsite, which have been investigated by comparative analysis of amino acid sequences and by computer-graphics techniques.
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PMID:Gabexate mesylate inhibition of serine proteases: thermodynamic and computer-graphics analysis. 310 78

Intramuscular administration of trypsin and kallikrein (andecaline) into rats contributed to more favourable development of acute traumatic pancreatitis. Trypsin and andecaline prevented the activation of proteinases in blood serum and pancreas and promoted an increase in content of trypsin inhibitor in blood serum. The proteinases efficiency appears to depend on elevation of general resistance of the organism to the trauma.
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PMID:[Effect of trypsin and kallikrein (andecalin) on the activity of proteolytic enzymes and their inhibitors in acute experimental pancreatitis]. 331 6

The effects of high-dose corticosteroids (HDC) on activities within the proteolytic cascade systems were studied in vitro and in vivo using chromogenic peptide substrate assays. In in vitro experiments 20 mg methylprednisolone sodium succinate (Solu-Medrol) per ml plasma significantly inhibited activation of plasma prekallikrein, prothrombin and plasminogen and reduced functional plasma kallikrein inhibition, antithrombin and antiplasmin activities. The effects of HDC on activities within these proteolytic cascade systems were further evaluated in experimental acute pancreatitis in pigs. Acute pancreatitis was induced by injection of Na-taurocholate into the pancreatic duct. Seven test animals received methylprednisolone sodium succinate 30 mg per kg intravenously for 30 minutes before the induction of pancreatitis as pretreatment. Eight animals remained untreated. Trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and mean arterial pressure (MAP) were monitored regularly before and during a 6 hour observation period. During untreated pancreatitis a reduction of PKK levels of about 40% were found, paralleled by an increased KK activity and a reduction of KKI capacity. Several of the animals experienced high TRY activities. The mortality rate was 63% (5 out of 8 animals). In the pretreated groups, all animals survived the observation period. CO and MAP were significantly less reduced than the untreated group at 6 hours. HDC was also found to reduce significantly plasma kallikrein activities in the peritoneal exudate compared with untreated animals. No changes in TRY activities were found in pretreated animals. Furthermore, plasma prekallikrein and functional plasma kallikrein inhibition values in the exudate were elevated significantly in HDC treated animals compared with untreated animals.
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PMID:Modulation of the proteolytic cascade systems by high dose corticosteroids. 391 8

The correlation between clinical course, protease inhibitors, complement and kinin activation was studied in vivo in 27 attacks of acute pancreatitis and also in vitro. The value of peritoneal lavage was retrospectively analyzed in 73 pancreatitis attacks. The effect of aprotinin was studied in vitro. Complement and kinin activation occurred in vitro when alpha-macroglobulin (alpha 2-M) concentration was below 35%, in spite of 90% free and reactive alpha 1-protease inhibitor. These low alpha 2-M levels were found in the general circulation in severe attacks. Functional alpha 2-M levels were lower than electroimmunoassay values during the acute disease. Complement and kinin activation was present both in blood and in peritoneal fluid. The extent of activation was closely correlated to the severity of the pancreatitis attack. Classical as well as alternative complement activation occurred. Kinin activation was caused by plasma kallikrein as well as by other kininogenases. Functional kallikrein inhibition was lower than electroimmunoassay values for the C1 inactivator. High levels of activated trypsin was found in complex with alpha 1-protease inhibitor in severe attacks. These findings together with the low functional alpha 2-M and a possible functional deficiency also of the C1 inactivator make trypsin-induced activation of the complement as well as the kinin system possible in acute pancreatitis. Changes in proteases and protease inhibitors were most pronounced in the peritoneal fluid, functional alpha 2-M and C1 inactivator being zero, indicating that the primary event occurs locally in and around the pancreas. Peritoneal lavage thus ought to be beneficial. The good results achieved with peritoneal lavage in the retrospective analysis of the 73 clinically severe attacks seem to verify this conclusion. The biochemical changes seen in vivo indicate alpha 2-M and C1 inactivator to be most important against proteolytic activation of the complement and kinin systems. Treatment with purified protease inhibitors might be beneficial. This also seems to be true of aprotinin, according to the in vitro results, provided very high doses are used. All antiprotease therapy seems to be most important intraperitoneally.
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PMID:Acute pancreatitis in man. A clinical and biochemical study of pathophysiology and treatment. 620 40

Changes 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. 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 peritoneal fluid, where kallikrein activity was above normal, while kininogen and kallikrein inhibition were nil in severe attacks. Both high and low molecular weight kininogen were decreased, denoting an activation also by kininogenases other than plasma kallikrein. These changes indicate an activation of the kallikreinkinin system in acute severe pancreatitis in man, especially in the abdominal cavity. Although there is a great deal of evidence for activation of the kinin system in experimental shock states in animals (1-4), there are to date rather few studies showing that such an activation takes place in human acute pancreatitis. This lack of clinical studies is mainly explained by the difficulty in measuring activated components of the system, especially since these components are rapidly inactivated in different ways in vivo (5).
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PMID:Changes in the kallikrein kinin system during acute pancreatitis in man. 620 88


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