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)

In 12 dogs with acute experimental pancreatitis (AEP) and 6 control animals the "free", "latent" and "total" activity of acid phosphatase, beta-glucuronidase and cathepsins in whole homogenates of the pancreas, in a lysosomal-enriched subfraction and the supernatant of pancreatic tissue was estimated. AEP was induced by injection of bile salts and thrombin solution into the pancreatic duct. In 6 dogs the protection with heparin (1.5 mg/kg/body weight) immediately after producing AEP was applied. In AEP without any protection the free activity of hydrolases in the whole homogenate (80--90%) and in the lysosomal enriched subfraction (75--90%) was higher than in the controls (60--70% and 55--75% respectively), suggesting an augmented lysosomal fragility during the course of AEP. Heparin depressed the free activity of hydrolases to 60--80% in whole homogenates, and 64--75% in the lysosomal enriched subfraction. The release of cathepsins during incubation of the lysosomal-enriched subfraction in acidic medium was lower in the group with heparin treatment. The data obtained suggest the stabilising effect of heparin on the lysosomes of the pancreas during acute experimental pancreatitis in dogs.
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PMID:The effect of heparin on lysosomes of the dog pancreas during acute experimental pancreatitis. 47 25

Alterations in coagulation factors have been reported during acute pancreatitis. Therefore the relationship of coagulation measurements to complications of pancreatitis was evaluated prospectively in 35 patients in whom 130 serial coagulation profiles were performed, consisting of fibrinogen, platelet count (PC), fibrinogen-fibrin-related-antigen (FR-antigen), prothrombin time (PT), partial thromboplastin time, thrombin time, euglobulin clot lysis, and Factors II, V and VII-X levels. During attacks of acute pancreatitis, over-all mean initial fibrinogen and PC of 268 mg. per 100 ml. and 214,000 per cubic millimiter rose significantly (p less than 0.005) to peaks of 362 mg. per 100 ml. and 477,800 per cubic millimeter by day 6 to 10. Mean initial FR-antigen of 4.8 microgram per milliliter rose to peak 7.4 microgram per milliliter on day 5. In 21 patients with mild pancreatitis, mean highest fibrinogen, PC, FR-antigen, and PT were 329 mg. per 100 ml., 361,500 per cubic millimeter, 5.3 microng per milliliter and 14.1 seconds. These values were significantly higher (p less than 0.05 to 0.01) in patients with severe pancreatitis, being 422 mg. per 100 ml. 528,000 per cubic millimeter, 13.7 microng per milliliter, and 15.5 seconds, respectively. Evaluation of the relationship of coagulation measurements to early clinical features showd that mean initial fibrinogen levels were significantly higher (p less than 0.05 to 0.01) in patients with initial amylase greater than 1,000 Somogyi units percent, serum glutamic oxaloacetic transaminase (SGOT) greater than 250 S.F.U. percent, and initial 72 hour PAO2 less than 75 mm. Hg. Early hypoxemia also correlated (p less than 0.05) with elevated initial FR-antigen levels. Impaired early renal function correlated (p less than 0.01) with elevated initial PC only. Early hypocalcemia did not correlate with coagulation measurements. These findings demonstrate that marked changes in coagulation parameters occur during acute pancreatitis and are related to over-all morbidity. Correlation of early coagulation measurements with amylase levels and with respiratory, renal, and hepatic dysfunction suggests that enzyme-related intravascular coagulation may be implicated in the pathogenesis of these complications of pancreatitis.
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PMID:The relationship of coagulation factors to clinical complications of acute pancreatitis. 85 Aug 68

The mean levels of fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT), and soluble fibrin (tPA method) in cancer patients (n = 32) were intermediate between those of patients with cerebral infarction and pancreatitis who had the most abnormal results and patients with myocardial infarction and pneumonia who had the least abnormal results. Patients with disseminated malignancies (n = 16) had significantly higher mean levels of FPA (10.6 vs. 5.3 nmol/l) and TAT (11.0 vs. 4.4 pmol/l) than patients with limited malignancies (n = 16). The difference in soluble fibrin (fibrin monomer, FM; 22.1 vs. 18.0 nmol/l) was not significant. The values of FPA, FM, and TAT in the patient population correlated significantly. There was a negative correlation between the level of antithrombin and test results for FPA (-0.69), FM (-0.48), and TAT (-0.38) in the cancer patients. Even cancer patients with locally limited disease may have elevated FPA, FM, and TAT test results, indicating a state of definite hypercoagulation.
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PMID:Indices of hypercoagulation in cancer as compared with those in acute inflammation and acute infarction. 228 6

The detection of TATC may inform about the presence of thrombin generation and, and hence of a pre-thrombotic status. An ELISA test (Enzygnst TAT) has been developed here in order to evaluate the predictive role played by TATC, and it was applied on 182 patients who distributed in 14 with cirrhosis of the liver, 11 with sepsis, 17 with chronic arterial insufficiency, 55 with neoplasms, 9 with thrombosis, 15 in postoperative period, 15 with pneumonia, 16 with disseminated intravascular coagulation (DIC), 14 with multiple injuries and 16 with pancreatitis. TATC levels were significantly increased in all groups with regard to the control group. Patients with thrombosis, sepsis, multiple injuries, DIC and in the postoperative period showed especially high TATC figures. No correlation between TATC and fibrinogen, platelet count, activated partial thromboplastin time or prothrombin complex assay was found in the post-operative patient-group. It was concluded that TATC are a good indicator of hypercoagulability.
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PMID:[Detection of thrombin-antithrombin complexes in hypercoagulability conditions. Analysis of 182 cases]. 229 Nov 47

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

4-(2-Succinimidoethylthio) phenyl 4-guanidinobenzoate (E-3123) potently inhibited trypsin, plasmin and thrombin with IC50 values of 3.9 x 10(-8) M, 9.5 x 10(-7) M and 1.9 x 10(-6) M, respectively. Experimental acute pancreatitis was induced by injection of a mixture of trypsin and taurocholate into the pancreas in rats and rabbits or by an application of a closed duodenal loop in dogs. Intravenous infusion of E-3123 at 0.03-0.3 mg/kg in rats or at 0.3-3.0 mg/kg in rabbits reduced mortality after the induction of pancreatitis in a dose-dependent manner. Light microscopy of the pancreas in the E-3123-treated rabbits revealed marked decrease in cell necrosis and acinar cell vacuolation. Increase in plasma lipase activities associated with the progression of pancreatitis in rabbits was also reduced by the infusion of E-3123. In dogs with pancreatitis, increases in serum trypsin and lipase activities were significantly reduced by infusion of E-3123 at 1.0 and 3.0 mg/kg. The efficacies of E-3123 in the in vivo experiments were higher than those of nafamostat mesilate. These results show that E-3123 may possess suppressing effects on pathogenesis and development of acute pancreatitis.
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PMID:[Effects of E-3123, a new protease inhibitor, on several protease activities and on experimental acute pancreatitis]. 341 Mar 75

Continuous arterio-venous haemofiltration (CAVH), a simple technique not employing pumps, was used for treatment of acute renal failure in 25 intensive care patients (mean age 52 +/- 16 [SD] years). Acute renal failure was due to trauma in 9 patients, occurred after surgery in 7 patients and was related to septicaemia in 5 patients, peritonitis in 2 patients and pancreatitis in one patient; in one patient acute renal failure developed during pregnancy after preexisting renal disease. Seventeen patients were oliguric and 8 patients were non-oliguric, with a mean daily urine output of 507 +/- 407 ml. At the start of CAVH the serum creatinine level was 511 +/- 198 mumol/l. The duration of treatment with CAVH was 1 to 36 days (average 9.3 days). Access to the circulation was by cannulation of the femoral artery and vein in 23 patients and by Scribner shunt in 2 patients. After an initial systemic dose of 2000 IU heparin, a continuous infusion of 250-1000 IU/hr into the arterial blood line was administered, adjusted to a partial thrombin time of 58 +/- 28 sec. With this heparin regimen a single haemofilter could be used for an average time of 2.6 +/- 1.2 days. The mean spontaneous filtration rate was 6 +/- 2 ml/min, resulting in the following serum levels: creatinine 490 +/- 187 mumol/l; urea 39 +/- 12.5 mmol/l; potassium 4.5 +/- 0.5 mmol/l. Nine catheter-associated complications occurred in 5 patients. The most important aspect of CAVH was its simplicity, optimal control of fluid balance and the possibility of unlimited parenteral nutrition. Uremia was adequately and continuously controlled. Prognosis of ARF was related to the patients' underlying illness.
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PMID:[Continuous arteriovenous hemofiltration for the treatment of acute kidney failure]. 398 93

In 22 dogs with acute experimental pancreatitis (AEP) the blood triglyceride (TG) levels, plasma post heparin lipolytic activity (PHLA), plasma inhibitors of PHLA and lipid electrophoresis were estimated. AEP was induced by injection of bile salts and thrombin into the pancreatic duct. In dogs treated with heparin in doses of 1.5 mg/kg body weight, hyperlipaemia was not found. In these animals the increase of PHLA inhibitors was evidently lower in comparison to untreated group. Our results indicate the preventive effect of heparin against disturbances of lipid metabolism in AEP.
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PMID:The effect of heparin on lipid metabolism in acute experimental pancreatitis (AEP). 741 42

This paper is concerned with a hypothesis that disturbance of free radical reactions may lead to abnormality of hemorheological properties in vivo, and so the free radicals generated in vivo may damage certain tissue cells indirectly by reducing the supply of oxygen and nutrients to these cells through slowing the circulation of blood. This hypothesis is based on the following evidence: A. We have found that the whole blood viscosity at low shear rate correlates to the lipid peroxidation in the patients suffering from certain cardio- or cerebrovascular diseases, and in dogs during liver ischemia reperfusion or hemorrhagic pancreatitis. B. Reports have shown that several alterations of hemorheological properties may take place as a result of free radical reactions, such as lipid peroxidation. For instance, lipid peroxidation may lead to decrease of deformability of red cells, increase of aggregation of red cells, formation of liquid thrombin, etc. C. We have demonstrated that some alterations of hemorheological properties involve the role of free radicals in rats suffering from intestinal ischemia/reperfusion. As evidence for this conclusion, superoxide dismutase (SOD) used as a specific scavenger of superoxide anion radical (O2-) can significantly prevent the intestinal ischemia/reperfusion induced changes of lipid peroxidation, red cell aggregation, Cassion's viscosity and whole blood viscosity at low shear rate in rats.
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PMID:A new hypothesis about the relationship between free radical reactions and hemorheological properties in vivo. 818 28

Antithrombin III (AT III) is the physiological inhibitor of thrombin and other serine proteases of the clotting cascade. In the development of sepsis, septic shock and organ failure, the plasma levels of AT III decrease considerably, suggesting the concept of a substitution therapy with the inhibitor. A decrease of AT III plasma levels might also be associated with other pathological disorders like trauma, burns, pancreatitis or preclampsia. Activation of coagulation and consumption of AT III is the consequence of a generalized inflammation called SIRS (systemic inflammatory response syndrome). The clotting cascade is also frequently activated after organ transplantation, especially if organs are grafted between different species (xenotransplantation). During the past years AT III has been investigated in numerous corresponding disease models in different animal species which will be reviewed here. The bulk of evidence suggests, that AT III substitution reduces morbidity and mortality in the diseased animals. While gaining more experience with AT III, the concept of substitution therapy to maximal baseline plasma levels (100%) appears to become insufficient. Evidence from clinical and preclinical studies now suggests to adjust the AT III plasma levels to about 200%, i.e., doubling the normal value. During the last few years several authors proposed that AT III might not only be an anti-thrombotic agent, but to have in addition an anti-inflammatory effect.
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PMID:Antithrombin III in animal models of sepsis and organ failure. 951 81


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