Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatitis was induced by injection of autologous bile into the main pancreatic duct of dogs. An initial fall in blood pressure was accompanied by appearance of large quantities of active trypsin, chymotrypsin, and elastase in pancreatic exudate with full saturation of protease inhibitors. The enzymes soon appeared in ascitic fluid and lymph, but only in the form of complexes with alpha1-antitrypsin, and alpha2-macroglobulin. No such complexes were detected in venous blood indicating short half-life in the circulation. These studies confirm the release of pancreatic enzymes during bile-induced pancreatitis, and quantify an important protective role for plasma protease inhibitors in this situation.
 ...
PMID:Release of proteolytic enzymes in bile-induced pancreatitis in dogs. 5 Sep 58

The association of chronic pancreatitis with diabetes is not very common. Men are the usual victims and ethylism the usual cause. The most common age of onset is between 40 and 50. Insulin treatment is much more frequent than for idiopathic diabetics. Diabetic heredity is probable. Calcifying pancreatitis is the most frequent form. Micro and macroangiopathic complications are found. A statistical comparative study with a matched series of idiopathic diabetics reveals no difference in the onset of vascular complications. The rate of triglycerides is statistically lower in pancreatitis (p less than 0.001). The other biological rates are the same (cholesterol, uricemy, alpha 2 macroglobulin). Diabetic stability is no more difficult to obtain than for idiopathic diabetics. In most cases the diet should be wide and alcohol must be prohibited.
 ...
PMID:[Diabetes and chronic pancreatitis. Report of twenty cases (author's transl)]. 23 6

Total protein, alpha1-antitrypsin, alpha2-macroglobulin, amylase, methemalbumin, tryptic amidase activity, radioimmunoassayable elastase 2, and three lysosomal hydrolases were determined in the ascites fluid from patients with acute pancreatitis. In eight patients methemalbumin was detected in ascites and serum, supporting the diagnosis of hemorrhagic pancreatitis. Significant levels (4-45 microgram/ml) of tryptic amidase activity were detected in ascites samples from all patients. Evidence is presented which demonstrates that the tryptic amidase activity is due to alpha2-macroglobulin-bound trypsin. Pancreatic elastase 2, determined with a new sensitive and specific radioimmunoassay, ranged from 400 to 2100 ng/ml in serum and from 650 to 4460 ng/ml in ascites fluid. Substantial amounts of alpha2-macroglobulin-bound trypsin and elastase 2, entering the circulation from the peritoneal cavity, might be responsible for certain serious complications seen in acute pancreatitis. However, with the exception of serum calcium and methemalbumin and the ascites fluid methemalbumin and total protein, none of the biochemical parameters studied showed a distinct correlation with the patient's outcome.
 ...
PMID:Studies on the ascites fluid of acute pancreatitis in man. 62 83

Assessment of the degree of severity of acute pancreatitis by means of biochemical parameters is still a subject of extensive studies. The purpose of the present study was a trial of evaluation of the diagnostic usefulness and prognostic value of certain tests for proteinase-anti-proteinase equilibrium and acute phase indices in acute pancreatitis in 52 patients (36 women and 16 men aged 22 to 83 years). The control group compared 29 healthy volunteers. The patients were classified according to the aetiology of the disease: pancreatitis connected with bile duct disease, alcoholic and non-classifiable, and another classification was based on the clinical course (medium severe, severe). Significantly higher concentration of immunoreactive trypsin (TLI) was found in the first two weeks in the group of severe disease as compared to the group with medium severe pancreatitis (p less than 0.01). TLI was significantly higher than in controls for 2 months after clinical recovery. The serum inhibitory capacity was significantly reduced in severe cases in relation to medium severe ones, particularly between 3 and 7 days of the disease (p less than 0.001). Similarly as trypsin concentration, reduced inhibitory capacity in relation to controls persisted for up to 2 months after pancreatitis. No significant differences were noted in the concentration of alpha 1 protease inhibitor and C3 and C4 complement components, in the studied groups. The serum alpha 2 macroglobulin level was significantly decreased between days 3 and 7 (p less than 0.05). The values of alpha 2 macroglobulin were correlated in that time with the values of the inhibitory capacity.
 ...
PMID:[Diagnostic usefulness and prognostic value of inhibitory capacity and other biochemical parameters of plasma in acute pancreatitis in humans]. 170 53

In uremic intoxication proteolytic activity in plasma and striated muscle is enhanced. To get further insight into the underlying mechanisms the neutral proteinases of polymorphonuclear (PMN) leukocytes were investigated in patients with acute and chronic renal failure. The following studies were performed: 1. Neutral proteolytic activity of PMN neutrophils in blood smears (according to Klessen, 1978). 2. Serum levels of elastase alpha 1 proteinase inhibitor complex (Neumann et al., 1981). In about half of the patients with chronic renal insufficiency on dietary treatment the proteolytic activity of PMN leukocytes (halo formation are due to digestion of erythrocytes and plasma) was reduced. The serum concentration of elastase alpha 1 proteinase inhibitor complex was normal in most subjects, but increased in 3 patients with the highest serum creatinine levels (greater than 13 mg/dl). In the patients with acute renal failure (ARF) of various origin (postoperatively, septicemia, pancreatitis or dye induced) halo formation was either reduced or absent. Serum elastase alpha 1 proteinase inhibitor was increased in 5/6 patients by a factor of two to four. Also in the 15 patients on regular hemodialysis treatment halo formation was substantially reduced, while the serum levels of elastase alpha 1 proteinase inhibitor complex was slightly increased. The finding of reduced proteolytic activity of PMN neutrophils in uremia is probably due to an enhanced release of proteinases into the circulation as indicated by the elevated serum levels of elastase alpha 1 proteinase inhibitor complex in some patients. The release of proteinases might be in part due to the effect of "uremic toxins". In the RDT patients the contact of the blood with the dialyzer (cuprophane) membrane might be an additional factor. In the patients with ARF the underlying disease (infection, shock, trauma) contributes to the release of proteinases. These disturbances may be harmful for the patient, if the blood concentration or function of the most important proteinase inhibitors (alpha 1 proteinase inhibitor, alpha 2 macroglobulin) is reduced.
 ...
PMID:Release of granulocyte neutral proteinases in patients with acute and chronic renal failure. 636 15

In acute pancreatitis, particularly in severe cases, polymorphonuclear neutrophil (PMN) elastase induces tissue damage in remote organs such as the lung, as well in the pancreas itself. Therefore, we examined the therapeutic effect of a specific synthetic inhibitor of PMN elastase (ONO-5046: Ono Pharmaceuticals, Osaka, Japan) on the lung, liver, and kidney, as well as pancreas, in severe hemorrhagic pancreatitis in dogs. Acute hemorrhagic pancreatitis was induced by the injection of a mixture of autologous bile and porcine trypsin into the main pancreatic duct. Lipopolysaccharide (LPS) was administered intravenously as a septic challenge. Two animal groups were used. In one group, continuous infusion of ONO-5046 was started prior to the injection of LPS (ONO group). In the other group (control), saline was infused instead. At the end of the experiment (330 min after the injection of bile and trypsin), the pancreas revealed severe hemorrhagic pancreatitis, and a large amount of bloody ascites had accumulated in the peritoneal cavity. The white blood cell count was markedly reduced in response to the induction of pancreatitis, and was decreased further by the septic attack, irrespective of the administration of ONO-5046, although the count increased again in the ONO group. Serum levels of amylase and alpha2-macroglobulin-trypsin complex increased similarly in both groups following administration of bile and trypsin. Serum Ca levels decreased in both groups. At the end of the experiment, the wet weight of the lung was slightly higher in the control group (without ONO-5046). Microscopically, the pancreas showed severe hemorrhage accompanied by extensive interstitial edema in both groups. The lung and liver demonstrated mild infiltration of inflammatory cells in the interstitium in both groups, although the inflammatory change in the liver was slightly milder in the ONO group. These findings indicate that severe hemorrhagic pancreatitis cannot be alleviated by the administration of a specific inhibitor of PMN elastase alone, although this may lessen damage to remote organs such as the liver and lung. The white blood cell count decreased markedly after the induction of acute pancreatitis, and much more after a septic challenge. This seems to be closely related to the accumulation of bloody ascites in the peritoneal cavity.
 ...
PMID:Effect of a specific synthetic inhibitor of neutrophil elastase (ONO-5046) on the course of acute hemorrhagic pancreatitis in dogs. 993 92

The pathophysiology of acute pancreatitis accompanied by chronic liver injury, and the therapeutic efficacy of prostaglandin (PG)E1 were studied experimentally in rats. Chronic liver injury was produced by subcutaneous administration of CCl4. Acute pancreatitis was induced by the closed duodenal loop (CDL) method, immediately after which PGE1 (60 ng/kg/min) was infused intravenously via the jugular vein. Serum levels of amylase, alpha2-macroglobulin-trypsin complex (alpha2M-TRY), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were determined before and at 3 and 6 h after the onset of acute pancreatitis. Rats without administration of CCl4 served as controls. Serum amylase levels were lower in the liver injury (LI) group than in the normal liver (NL) group at 3 and 6 h. PGE1 had no effect on amylase levels in either group. Serum alpha2M-TRY levels were similar in the two groups at 3 h, but significantly higher in LI than in NL at 6 h. PGE1 tended to decrease alpha2M-TRY levels only in LI. Serum CRP levels were significantly more elevated in LI than in NL at 0, 3, and 6 h. PGE1 decreased CRP levels only in LI. Serum TNF-alpha concentrations were higher in LI, especially at 6 h. PGE1 reduced TNF-alpha levels in LI. Pancreatitis severity scores were significantly higher in LI. PGE1 significantly decreased the severity scores only in LI. Fat necrosis scores were significantly lower in LI. Histologically, interstitial edema was much more prominent in NL than in LI, whereas interstitial hemorrhage was more severe in LI at 3 and 6 h. PGE1 lessened the hemorrhage in LI. The extent of both vacuolization and necrosis of acinar cells was similar for both groups and tended to be improved by PGE1. It is concluded that acute pancreatitis becomes much more serious in the presence of chronic liver injury, and that PGE1 can ameliorate the exacerbated lesions, probably by improvements in blood flow through the pancreatic tissue.
 ...
PMID:Exacerbation of acute pancreatitis in the presence of chronic liver injury in rats, with special reference to therapeutic efficacy of prostaglandin E1. 1043 68

Mice deficient in either or both mouse alpha2-macroglobulin (MAM) and murinoglobulin-1 (MUG1) were generated and proved phenotypically normal under standard conditions. Acute pancreatitis was induced with a diet deficient in choline and methionine, supplemented with ethionine. The mortality was less than 25% in wild-type mice, as opposed to at least 56% in knockout mice, and was highest (70%) in MAM-/- mice, with earliest onset at 2 days. Plasma amylase and lipase levels were increased, but pancreatic tissue appeared histologically variable in individual mice. The clinical symptoms were most severe in MAM-/- mice and, surprisingly, were not aggravated in the double knockout mice, suggesting that the lack of proteinase inhibition capacity was not the major problem. Therefore, we analyzed the expression of 21 different cytokines and polypeptide factors in the pancreas of all experimental groups of mice. Interleukin-1-receptor antagonist mRNA was consistently induced by the diet in the pancreas of MAM-/- mice, and transforming growth factor-beta, tumor necrosis factor-alpha, tumor necrosis factor-beta, beta-lymphotoxin, and interferon-gamma mRNA levels were also increased. The data demonstrate the important role of alpha2-macroglobulin (A2M) in acute pancreatitis as both a proteinase inhibitor and a cytokine carrier. Mice deficient in MAM and/or MUG thus offer new experimental models for defining in vivo the role of the macroglobulins in pancreatitis and in other normal and pathological processes.
 ...
PMID:alpha2-macroglobulin- and murinoglobulin-1- deficient mice. A mouse model for acute pancreatitis. 1048 56

In this study we determined the clinical accuracy of alpha2-macroglobulin, alpha-amylase, C-reactive protein, lipase, non-esterified fatty acids, pancreatic alpha-amylase and phospholipase A in the diagnosis and prognosis of acute pancreatitis in a group of patients with acute abdominal pain using receiver operator characteristic curve analysis. We investigated 59 patients with acute pancreatitis and 72 patients with extrapancreatic diseases of gastrointestinal origin. On the basis of initial enzyme activities, at cut-offs of 245 U/l for amylase, 656 U/l for lipase, and 182 U/l for pancreatic alpha-amylase, the diagnostic efficiencies were 0.993, 0.980, and 0.975, respectively. Receiver operator characteristic curve analysis showed the same diagnostic accuracies. We evaluated the accuracy of serum alpha2-macroglobulin, C-reactive protein, non-esterified fatty acids and phospholipase A for differentiation between acute necrotizing pancreatitis and acute oedematous pancreatitis. C-reactive protein had the highest prognostic accuracy of the parameters studied (the area under curve = 0.9082) and at a cut-off value of 126 mg/l, sensitivity and specificity were 0.759 and 0.912, respectively. The role of the clinical laboratory in the investigation of patients with acute pancreatitis continues to evolve and biochemical parameters are a good diagnostic and prognostic option.
 ...
PMID:Biochemical evaluation of patients with acute pancreatitis. 1115 45

At modelling streptozotocin and alloxan diabetes mellitus in rats we have detected an imbalance between elastase and its inhibitors (alpha 1 inhibitor of protein kinases, alpha-2 macroglobulin, acid-thermoresistant inhibitors) in tissues of the pancreas. The contribution of proelactase decreased but that of an active form of protein kinase increased; the content of alpha 1 inhibitor of protein kinase and alpha 2 macroglobulin reduced, however, the contribution of the acid-thermoresistant inhibitors in the pancreatic tissues increased. Imbalance in the system elastase-inhibitors, shown at the model of diabetes mellitus, may be an important mechanism of an exocrine insufficiency of the pancreas which results in pancreatitis.
 ...
PMID:[Elastolytic system of the pancreas in modelling diabetes mellitus]. 1244 9


1