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)

Overproduction of tumor necrosis factor (TNF-), interleukin-1beta (IL-1beta), and nitric oxide (NO) is believed to be detrimental during the progression of acute pancreatitis, yet little is known about the hepatic production of these mediators and their role in mediating pancreatitis-induced hepatic dysfunction. Rats were randomized to receive a single intraperitoneal injection of the macrophage-pacifying compound, CNI-1493 (1.0 mg/kg), or vehicle 1 hour before the induction of retrograde bile salt pancreatitis. Sham-operated animals served as controls. Animals were killed 18 hours later, with serum and livers harvested to determine the degree of hepatocellular injury and the induction of TNF-, IL-1beta, and inducible nitric oxide synthase (iNOS). In addition, serum TNF- and nitrites (end-product of NO breakdown) were determined in each group to assess the mechanism of action of CNI-1493. TNF-, IL-1beta, and iNOS gene expression (by reverse-transcription polymerase chain reaction) as well as aspartate transaminase (AST), alanine transaminase (ALT), and lactic dehydrogenase (LDH) (but not alkaline phosphatase [ALP]) increased following the development of pancreatitis (all P < .05). Macrophage pacification significantly prevented the induction of TNF- and IL-1beta mRNA (but not iNOS), resulting in lessened serum AST, ALT, and LDH (all P < .05). Serum TNF- protein and nitrites correlated with gene induction in that both were increased following the onset of pancreatitis, and TNF- protein production was significantly attenuated in animals receiving CNI-1493. Hepatocellular, but not bile duct, injury occurs during experimental pancreatitis that is associated with hepatic TNF-, IL-1beta, and iNOS mRNA gene induction, as well as TNF- protein and nitrite production. Preventing the production of TNF- and IL-1beta by macrophage pacification attenuates the hepatocellular damage, suggesting that these mediators play a role in pancreatitis-induced hepatic injury.
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PMID:Macrophage pacification reduces rodent pancreatitis-induced hepatocellular injury through down-regulation of hepatic tumor necrosis factor alpha and interleukin-1beta. 979 13

It was reported that free fatty acids degraded from triglycerides by lipase may play a major role in acute necrotizing or hyperlipidemia-induced pancreatitis. We hypothesized that this injury may be related to the peroxidation of cell membrane phospholipids and tested this hypothesis using isolated pancreatic acini. Pancreatic acini were prepared from male Sprague-Dawley rats by collagenase digestion. Linoleic acid was added (0.1-1.0 mM) to the acinar cell suspension to induce cell injury. Acinar cell damage was measured by lactate dehydrogenase release and by trypan blue exclusion. Phosphatidylcholine hydroperoxide and alpha-tocopherol in the acinar cells were measured. Protective effects of alpha-tocopherol (0.5, 5.0 mM) against this type of cell injury were also evaluated. When isolated acinar cells were treated with linoleic acid, a significant decrease in viability was observed in a time- and dose-dependent manner. In addition, the levels of phosphatidylcholine hydroperoxide after treatment of 0.5 mM of linoleic acid were increased and levels of alpha-tocopherol were decreased significantly. alpha-Tocopherol significantly ameliorated both cellular injury (p < 0.01) and increases in phosphatidylcholine hydroperoxide (p < 0.01). These data suggest that lipid peroxidation of the cellular membrane is an important component of the pancreatic cell injury mediated by free fatty acids.
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PMID:Involvement of lipid peroxidation in free fatty acid-induced isolated rat pancreatic acinar cell injury. 982 Nov 80

The mechanisms responsible for intrapancreatic digestive enzyme activation as well as the relationship between that activation and cell injury during pancreatitis are not understood. We have employed an in vitro system in which freshly prepared pancreatic acini are exposed to a supramaximally stimulating concentration of the CCK analog caerulein to explore these issues. We find that in vitro trypsinogen activation depends on the continued presence of Ca2+ in the suspending medium and that it is half-maximal in the presence of 0.3 mM Ca2+. Caerulein-induced trypsinogen activation can be halted by removal of Ca2+ from the suspending medium or by chelation of intracellular Ca2+. Increasing intracellular Ca2+ with either ionomycin or thapsigargin does not induce trypsinogen activation. We have monitored cell injury by measuring the leakage of lactate dehydrogenase (LDH) from acini and by quantitating intercalation of propidium iodide (PI) into DNA. Leakage of LDH and intercalation of PI in response to supramaximal stimulation with caerulein can be detected only after caerulein-induced trypsinogen activation has already occurred, and these indications of cell injury can be prevented by addition of a cell-permeant protease inhibitor. Our findings indicate that caerulein-induced intra-acinar cell activation of trypsinogen depends on a rise in intracellular Ca2+, which reflects entry of Ca2+ from the suspending medium. Intra-acinar cell activation of trypsinogen is an early as well as a critical event in pancreatitis. The subsequent cell injury in this model is mediated by activated proteases.
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PMID:Secretagogue-induced digestive enzyme activation and cell injury in rat pancreatic acini. 1019 25

The main purpose of this study was to investigate the influence of nimodipine, a calcium channel blocker (CCB) and thyroid-releasing hormone (TRH) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. CCB decreased blood pressure in rats in the control and pancreatitis groups. TRH corrected this decrease. CCB alone had no effect on PO2 serum amylase activity, calcium concentration, liver transaminases, lactate dehydrogenase or the degree of pancreatic damage, except for the serum concentration of creatinine. CCB+TRH reduced the concentrations of serum urea and creatinine, the degree of pancreatic damage, and increased PO2 and serum calcium concentration. CCB and CCB+TRH had no effect on pancreatic myeloperoxidase activity. CCB alone had no effect on the course of ANP, but CCB+TRH had beneficial effects on the course of the ANP and various systems.
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PMID:The effects of calcium channel blocker and thyrotropin releasing hormone on acute necrotizing pancreatitis in rats. 1049 74

Sediment ingestion has recently been identified as an important exposure route for toxicants in waterfowl. The effects of lead-contaminated sediment from the Coeur d'Alene River Basin (CDARB) in Idaho on posthatching development of Canada geese (Branta canadensis) were examined for 6 wk. Day-old goslings received either untreated control diet, clean sediment (48%) supplemented control diet, or CDARB sediment (3449 microg/g lead) supplemented diets at 12%, 24%, or 48%. The 12% CDARB diet resulted in a geometric mean blood lead concentration of 0.68 ppm (ww), with over 90% depression of red blood cell ALAD activity and over fourfold elevation of free erythrocyte protoporphyrin concentration. The 24% CDARB diet resulted in blood lead of 1.61 ppm with decreased hematocrit, hemoglobin, and plasma protein in addition to the effects just described. The 48% CDARB diet resulted in blood lead of 2.52 ppm with 22% mortality, decreased growth, and elevated plasma lactate dehydrogenase-L (LDH-L) activity. In this group the liver lead concentration was 6.57 ppm (ww), with twofold increases in hepatic lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) and in reduced glutathione concentration; associated effects included elevated glutathione reductase activity but lower protein-bound thiols concentration and glucose-6-phosphate dehydrogenase (G-6-PDH) activity. The kidney lead concentration in this group was 14.93 ppm with subacute renal tubular nephrosis in one of the surviving goslings. Three other geese in this treatment group exhibited calcified areas of marrow, and one of these displayed severe chronic fibrosing pancreatitis. Lead from CDARB sediment accumulated less readily in gosling blood and tissues than reported in ducklings but at given concentrations was generally more toxic to goslings. Many of these effects were similar to those reported in wild geese and mallards within the Coeur d'Alene River Basin.
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PMID:Developmental toxicity of lead-contaminated sediment in Canada geese (Branta canadensis). 1070 32

A squirrel monkey (Saimiri sciureus) presented with wasting, vomiting and diarrhoea. Haematology revealed elevation of creatinine phosphokinase, lactic dehydrogenase, alanine aminotransferase, amylase and lipase, together with azotaemia and hypoalbuminaemia. Prominent findings were chronic pancreatitis with acinar and ductal plugs, granulomatous and necrotizing peripancreatic steatitis, degenerative myopathy, testicular atrophy, candidiasis and bacterial necrotizing glossitis. Antioxidant analyses revealed low concentrations of serum vitamin E (and apparently A), hepatic selenium and hair zinc. Pancreatitis may have caused malabsorption and maldigestion, associated with deficiency of multiple antioxidants.
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PMID:Antioxidant status in a squirrel monkey (Saimiri sciureus) with chronic pancreatitis and degenerative myopathy. 1103 77

There are a few prospective studies assessing the severity of acute pancreatitis with exclusive criteria for biliary etiology. In a cohort prospective study, Ranson (biliary etiology), Glasgow-modified, APACHE-II, and APACHE-O prognostic criteria were assessed in 65 patients with acute biliary pancreatitis (ABP). Local complications such as necrosis with fluid peripancreatic collection (3 patients), fluid collection with pancreas enlargement (3 patients), pancreatic fistula (1 patients), and pancreatic pseudocyst (1 patients); and organic failure such as renal (5 patients), hemodynamic (3 patients), and respiratory (3 patients) were found. The prognostic criteria performance, according to parameter number or positive variables evidenced that relative risk (RR) varied from 4.7 to 11.2, sensibility from 33.3% to 83.3%, specificity from 79.2% to 98.1%, positive predictive value from 45.0% to 83.3%, negative predictive value from 86.4% to 95.5%, and accuracy from 78.5% to 89.6%. In isolation, most important parameters correlated to severity included white blood cell count >18,000/mm3, lactate dehydrogenase (LDH) >400 UI/l, 10% drop of the hematocrit, serum calcium <8 mg/dl, increase of urea nitrogen >2 mg/dl, aspartate aminotransferase (AST) >200 mg/dl, LDH >600 UI/l, white blood cell count >15,000/mm3, urea >45 mg/dl, arterial pH < or = 7.33 or > or = 7.49, creatinin < or = 0.6 or > or = 1.4, hematocrit < or = 30 or > or = 45.9, white blood cell count < or = 3,000/mm3 or > or = 14,900/mm3. Ranson, Glasgow-modified, APACHE-II, and APACHE-O acute biliary pancreatitis severity criteria all present good sensibility and excellent specificity.
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PMID:Evaluation of Ranson, Glasgow, APACHE-II, and APACHE-O criteria to predict severity in acute biliary pancreatitis. 1199 72

BACKGROUND: The routine use of serum elastase-1 in patients, pre- and post-endoscopic retrograde cholangiopancreatography (ERCP), has been strongly supported but not sufficiently correlated with diagnosis, patient outcome/prognosis, or routine markers such as serum amylase. The value of serum elastase-1 post-ERCP, as far as clinical diagnosis and prognosis is concerned, was tested and compared with serum amylase in terms of sensitivity, specificity, positive prognostic value (PPV), and negative prognostic value (NPV). METHODS: In a prospective study of 38 consecutive patients undergoing ERCP, we assessed the following biochemical parameters 24 h before ERCP and 2 and 18 h after ERCP: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), alkaline phosphatase (ALP), amylase (AMS), lactate dehydrogenase (LDH), and pancreatic elastase-1. RESULTS: Statistically significant changes were found between pre-ERCP and 18-h post-ERCP in elastase-1 (P=0.009), amylase (P=0.016), gamma-GT (P=0.04), and ALP (P=0.04). Changes between 2-h and 18-h post-ERCP in all parameters tested were not statistically significant. No statistical significance was found between any biochemical parameter and specific ERCP diagnosis. CONCLUSIONS: This study showed that 2-h post-ERCP serum elastase-1 was 100% specific for post-ERCP pancreatitis or other underlying severe pathology while, at the same time, amylase was only 50% specific. The specificity of serum elastase-1 still remained high (87.5%) 18-h post-ERCP, while amylase only had a specificity of 25% at that time. In contrast, amylase had a sensitivity of 83.3 and 90% in the 2-h and 18-h post-ERCP serum samples, while elastase-1 only had a sensitivity of 56.7 and 73.3%, respectively.
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PMID:The true value of serum elastase-1 in endoscopic retrograde cholangiopancreatography (ERCP). 1214 13

Cyclooxygenase-2 (COX-2), a widely distributed enzyme, plays an important role in inflammation. We have studied the role of COX-2 in acute pancreatitis and pancreatitis-associated lung injury using both the pharmacological inhibition of COX-2 and genetic deletion of COX-2. Pancreatitis was induced in mice by 12 hourly injections of cerulein. The severity of pancreatitis was assessed by measuring serum amylase, pancreatic trypsin activity, intrapancreatic sequestration of neutrophils, and acinar cell necrosis. The severity of lung injury was evaluated by measuring lactate dehydrogenase levels in the bronchoalveolar lavage fluid and by quantitating neutrophil sequestration in the lung. In both the pharmacologically inhibited and genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was reduced compared with the noninhibited strains of COX-2-sufficient mice. This reduction in injury indicates that COX-2 plays an important proinflammatory role in pancreatitis and its associated lung injury. Our findings support the concept that COX-2 inhibitors may play a beneficial role in the prevention of acute pancreatitis or in the reduction of its severity.
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PMID:Inhibition of cyclooxygenase-2 ameliorates the severity of pancreatitis and associated lung injury. 1238 31

Endoscopic retrograde cholangiopancreatography (ERCP), together with its substantial therapeutic capabilities, carries a higher potential for complications than other endoscopic procedures. Common major complications specific to pancreaticobiliary instrumentation include pancreatitis, post-sphincterotomy hemorrhage, perforation, and cholangitis with or without systemic sepsis. Two patients underwent therapeutic ERCP for recurrent episodes of abdominal pain and elevation of hepatobiliary enzymes. Endoscopic sphincterotomy was difficult and prolonged. The calculi were successfully extracted by sweeping the choledochus with a balloon-tipped catheter or basket in both cases. The patients experienced postprocedure diffuse abdominal pain unassociated with nausea or vomiting. Laboratory data showed normal serum amylase and lipase 2, 6, and 18 h after the end of procedure, a fall in hematocrit level, and an increase of indirect bilirubin and lactic dehydrogenase. The abdominal pain subsided in 4 to 6 h. The hematocrit level remained stable during the next 3 days, and the patients were very well when discharged. Examination of glucose-6-phosphate dehydrogenase (G-6PD) enzyme levels in red cells 20 days later showed complete enzyme deficiency. This report highlights the importance of examining G-6PD deficiency in patients with post-ERCP abdominal pain, normal serum amylase and lipase, and laboratory findings of hemolysis.
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PMID:Hemolysis caused by G-6PD deficiency after a difficult and prolonged therapeutic endoscopic retrograde cholangiopancreatography. 1272 87


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