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)

Serum immunoreactive trypsin (IRT) determination has been recommended as a screening test in chronic pancreatitis. Using a commercial radioimmunoassay kit (RIA--gnost Trypsin; Behring-Werke, Marburg/Lahn, FRG) the interassay coefficient of variation was 26--44% for three different test sera. Gel filtration chromatography profiles revealed immunoreactivity in the position of 125I-trypsin and (less than 50%) in the void volume. The test was evaluated in controls (n = 90), chronic relapsing pancreatitis (CRP;n = 60) and after total pancreatectomy (n = 5). In 65% of the CRP cases decreased IRT values were found, whereas during acute attacks of CRP supranormal and normal values were found. After total pancreatectomy IRT levels were undetectable. It is concluded that the sensitivity of this IRT test is limited and that the available test system needs improvement.
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PMID:Trypsin radioimmunoassay in the diagnosis of chronic pancreatitis. 739 44

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

A 48-year-old man was admitted for the evaluation of a massive left pleural effusion. Thoracenthesis yielded a bloody excudate with a high percentage of eosinophils (27%) and high values of pancreatic enzymes (amylase 16,000 Somogyi, Elastase 35,000 ng/dl, Lipase 12,800 U/l, Trypsin 77,000 ng/ml). The amylase isozyme of the exudate was 100% pancreatic-type fraction. The blood showed no eosinophilia (4%). A computed tomographic scan and magnetic resonance image of the abdomen revealed a pancreatic pseudocyst in contact with the diaphragm, and thrombi in the inferior vena cava and the splenic vein. After pancreatic cystectomy and splenectomy, the pleural effusion resolved rapidly. Eosinophilic pleural effusion has been reported as a complication of several disorders: pneumonia, lung carcinoma, pulmonary tuberculosis, and pulmonary infarction. However, we know of no previous report of eosinophilic pleural effusion with pancreatitis. In this case, it is interesting that the massive eosinophilic pleural effusion associated with chronic pancreatitis resolved immediately after the operation, and the patient was discharged.
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PMID:[A case of chronic pancreatitis with eosinophilic pleural effusion]. 766 23

This study compares the susceptibility of pancreatic acinar cells and zymogen granules against oxidative injury and analyzes the mechanisms involved. Zymogen granules and acinar cells, isolated from rat pancreas, were exposed to a reaction mixture containing xanthine oxidase, hypoxanthine, and chelated iron. Cell function and viability were assessed by various techniques. Trypsin activation was quantified by an Elisa for trypsinogen activating peptide. Integrity of granules was determined by release of amylase. The reaction mixture rapidly generated radicals as assessed by deoxyribose and luminol assays. This oxidative stress caused lysis of granules in a matter of minutes but significant cell death only after some hours. Nevertheless, radicals initiated intracellular vacuolization, morphological damage to zymogen granules and mitochondria, increase in trypsinogen activating peptide, and decrease in ATP already after 5-30 min. Supramaximal caerulein concentrations also caused rapid trypsin activation. Addition of cells but not of granules reduced deoxyribose oxidation, suggesting that intact cells act as scavengers. Caerulein pretreatment only slightly increased the susceptibility of cells but markedly that of granules. In conclusion, isolated zymogen granules are markedly more susceptible to oxidative injury than intact acinar cells, in particular, in early stages of caerulein pancreatitis. The results show that oxidative stress causes a rapid trypsin activation that may contribute to cell damage by triggering autodigestion. Zymogen granules and mitochondria appear to be important targets of oxidative damage inside acinar cells. The series of intracellular events initiated by oxidative stress was similar to changes seen in early stages of pancreatitis.
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PMID:Oxidative injury to isolated rat pancreatic acinar cells vs. isolated zymogen granules. 874 74

The role of oxygen-derived free radicals in pancreatitis after pancreas transplantation was examined in a porcine pancreatic transplantation model. Trypsin activation, protease inhibitor consumption, kininogen consumption, and postoperative graft function were investigated in 24 pigs subjected to whole organ pancreaticoduodenal transplantation. The animals were divided into one control group and two groups treated with free radical scavengers. One group was given allopurinol, and one group was treated with superoxide dismutase in combination with catalase. In the early phase (within 1 hr) after reperfusion, no differences were seen between the groups as to protease activation. Neither trypsin-protease inhibitor imbalance nor any signs of kininogen consumption were seen. In a later phase (1-3 days after the transplantation), the trypsin activation, measured as high molecular weight immunoreactive cationic trypsin in plasma, was significantly less pronounced in allopurinol-treated animals. This finding indicates a less severe form of reperfusion pancreatitis in this group compared with the other groups. A tendency toward better function in the allopurinol-treated group was also seen. We conclude that oxygen-derived free radicals seem to be of importance in the development of reperfusion pancreatitis after pancreas transplantation in the pig. We also conclude that allopurinol, but not superoxide dismutase/catalase, possibly due to the administration regimens used in this series, is able to attenuate the trypsin activation and the development of pancreatitis in the later phase in this model.
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PMID:Role of oxygen-derived free radicals in protease activation after pancreas transplantation in the pig. 948 64

Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved by trypsin within the NH2-terminus, exposing a tethered ligand that binds and activates the receptor. We examined the secretory effects of trypsin, mediated through PAR-2, on well-differentiated nontransformed dog pancreatic duct epithelial cells (PDEC). Trypsin and activating peptide (AP or SLIGRL-NH2, corresponding to the PAR-2 tethered ligand) stimulated both an 125I- efflux inhibited by Ca2+-activated Cl- channel inhibitors and a 86Rb+ efflux inhibited by a Ca2+-activated K+ channel inhibitor. The reverse peptide (LRGILS-NH2) and inhibited trypsin were inactive. Thrombin had no effect, suggesting absence of PAR-1, PAR-3, or PAR-4. In Ussing chambers, trypsin and AP stimulated a short-circuit current from the basolateral, but not apical, surface of PDEC monolayers. In monolayers permeabilized basolaterally or apically with nystatin, AP activated apical Cl- and basolateral K+ conductances. PAR-2 agonists increased [Ca2+]i in PDEC, and the calcium chelator BAPTA inhibited the secretory effects of AP. PAR-2 expression on dog pancreatic ducts and PDEC was verified by immunofluorescence. Thus, trypsin interacts with basolateral PAR-2 to increase [Ca2+]i and activate ion channels in PDEC. In pancreatitis, when trypsinogen is prematurely activated, PAR-2-mediated ductal secretion may promote clearance of toxins and debris.
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PMID:Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2. 991 38

Trypsin and chymotrypsin readily bind to human erythrocyte ghosts and to resealed right-side-out ghosts, but not to intact erythrocytes, as followed with [3H]trypsin and [3H]chymotrypsin and with cold proteases in a caseinolytic assay. The proteases freely reacted with casein in the presence of intact cells. Trypsin activated trypsinogen over an 8-hr time course at a faster rate in the presence of erythrocytes than in the absence thereof, after a slight initial delay. Trypsinogen did not bind to intact erythrocytes, thereby behaving comparably to trypsin. These results suggest that different microenvironments exist about the erythrocyte ghosts and the intact erythrocytes, thereby permitting the proteases to bind to the former but not to the latter. Hence, in the absence of considerable ghosts in circulating blood, which may mask the binding site of the proteases, the proteases may be more readily accessible for interaction with circulating serpins, leading to inactivation of the proteases and protection from their degradative potential. The presence of the serpins in circulating blood may assist in the control of the degradative power of the pancreatic proteases in pancreatitis and may negatively modulate such processes as thrombosis, activation of the complement system, and vascular remodeling.
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PMID:Membrane-protease interactions. III: A consideration of the difference in binding potential of pancreatic proteases to erythrocytes and erythrocyte ghosts. 1050 13

Hereditary pancreatitis (HP) is clinically indistinguishable from pancreatitis with other causes. Patients with HP have an increased chance of developing pancreatitis. Mutations in the cationic trypsinogen gene appear to cause most HP, although there is evidence for mild genetic heterogeneity with defects in other genes. Trypsin stabilization and protection from autolysis appear to play a central role in the pathogenesis of pancreatitis. The role of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) as well as the pancreatic secretory trypsin inhibitor (PSTI) in patients with pancreatitis is intriguing but as yet incompletely understood. Genetic testing may help to identify and manage patients with HP. Healthcare professionals should understand the elements necessary for obtaining informed consent for patients undergoing these tests, the limits in interpreting test results, and the psychosocial issues that may arise from genetic testing.
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PMID:Genetic testing in acute and chronic pancreatitis. 1127 78

A group of 16-kDa proteins, synthesized and secreted by rat pancreatic acinar cells and composed of pancreatic stone protein (PSP/reg) and isoforms of pancreatitis-associated protein (PAP), show structural homologies, including conserved amino acid sequences, cysteine residues, and highly sensitive N-terminal trypsin cleavage sites, as well as conserved functional responses in conditions of pancreatic stress. Trypsin activation of recombinant stress proteins or counterparts contained in rat pancreatic juice (PSP/reg, PAP I and PAP III) resulted in conversion of 16-kDa soluble proteins into 14-kDa soluble isoforms (pancreatic thread protein and pancreatitis-associated thread protein, respectively) that rapidly polymerize into insoluble sedimenting structures. Activated thread proteins show long lived resistance to a wide spectrum of proteases contained in pancreatic juice, including serine proteases and metalloproteinases. In contrast, PAP II, following activation with trypsin or pancreatic juice, does not form insoluble structures and is rapidly digested by pancreatic proteases. Scanning and transmission electron microscopy indicate that activated thread proteins polymerize into highly organized fibrillar structures with helical configurations. Through bundling, branching, and extension processes, these fibrillar structures form dense matrices that span large topological surfaces. These findings suggest that PSP/reg and PAP I and III isoforms consist of a family of highly regulated soluble secretory stress proteins, which, upon trypsin activation, convert into a family of insoluble helical thread proteins. Dense extracellular matrices, composed of helical thread proteins organized into higher ordered matrix structures, may serve physiological functions within luminal compartments in the exocrine pancreas.
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PMID:A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. 1127 30

Heat shock proteins (HSPs) are necessary in the synthesis, degradation, folding, transport, and translocation of different proteins. It is well known that the increased expression of HSPs may have a protective effect against cerulein-induced pancreatitis in rats or against choline-deficient ethionine-supplemented diet model pancreatitis in mice. The aim of this study was to investigate the potential effects of HSP preinduction by cold or hot water immersion on trypsin-induced acute pancreatitis in rats. Trypsin was injected into the interlobular tissue of the duodenal part of the pancreas at the peak level of HSP synthesis, as determined by Western blot analysis. The rats were sacrificed by exsanguination through the abdominal aorta 6 h after the trypsin injection. The serum amylase activity, the tumor necrosis factor-alpha, interleukin-1, and interleukin-6 levels, the pancreatic weight/body weight ratio, and the pancreatic contents of DNA, protein, amylase, lipase, and trypsinogen were measured. A biopsy for histology was taken. Hot water immersion significantly elevated the HSP72 expression, while cold water immersion significantly increased the HSP60 expression. Cold water immersion pretreatment ameliorated the pancreatic edema in trypsin-induced pancreatitis, however this was not due to the HSP60. Hot water immersion pretreatment did not have any effect on the measured parameters in trypsin-induced pancreatitis. The findings suggest that the induction of HSP60 or HSP72 are not enough to protect rats against the early phase of this localized necrohemorrhagic pancreatitis model.
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PMID:Induction of heat shock proteins fails to produce protection against trypsin-induced acute pancreatitis in rats. 1214 32


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