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)

1. The time course of iron overload of the pancreas in hypotransferrinaemic mice maintained on a standard rodent diet was compared with biochemical and histological markers of tissue damage. 2. Pancreatic iron levels increased linearly from weaning till 9 months of age [73.3 nmol/mg of tissue (SEM 9.9; n = 5) compared with 0.9 nmol/mg of tissue (SEM 0.1; n = 4) in age-matched controls] then decreased linearly till at least 18 months of age. 3. Investigation of tissue distribution of newly absorbed radioiron suggested that significant redistribution of iron from liver to pancreas (rather than direct dietary iron sources) must be invoked to explain the rate of pancreatic iron loading in hypotransferrinaemic mice. 4. Pancreatic epithelial cells first showed altered morphology at 9 months of age. At 12 months of age, the pancreatic epithelium had developed a micronodular appearance, with large numbers of acini replaced by atrophic, degenerated acinar cells. Increased collagen fibre deposition was evident by trichrome staining and by electron microscopy. Biochemical markers of pancreatitis (serum lipase, tissue pancreatitis-associated protein mRNA) were elevated before 9 months of age, whereas the levels of pancreatic amylase mRNA declined from 9 months of age. 5. The data suggest that iron loading of hypotransferrinaemic mouse pancreas proceeds up to a threshold level at 9 months of age followed by a progressive atrophy of secretory epithelium. The hypotransferrinaemic mouse pancreas is a useful model system for investigation of parenchymal cell damage by iron.
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PMID:Time-course of iron overload and biochemical, histopathological and ultrastructural evidence of pancreatic damage in hypotransferrinaemic mice. 948 91

For a substantial number of patients with acute pancreatitis, no recognizable causes can be identified and such cases are called "idiopathic". With the introduction of duodenal bile collection for microscopic examination, it became possible to detect minor constituents of the bile, such as cholesterol and/or calcium bilirrubinate crystals. The mechanism by which crystals produce pancreatitis seems to be related to migration of aggregate crystals through the papilla, inducing papillary trauma or temporary impaction which can cause a biliopancreatic reflux. We now report a series of 45 patients with acute pancreatitis idiopathic, 120 with gallstones and 22 alcoholic. Of the patients with idiopathic pancreatitis whom we studied by biliary drainages, 22 were found to have abnormal drainages (MC+) (20 cholesterol crystals and 2 calcium bilirrubinate), 9 patients had more than 10 crystals per slide. The microcrystals positive (MC+) group had significantly higher values for AST (69.8 +/- 1.7) (mean +/- SEM), ALT (123.3 +/- 28.1), FA (252 +/- 28.1), G-GT (144.6 +/- 26.7) and BT (1.83 +/- 0.37) than the microcrystals negative group: AST (19.6 +/- 2.5), ALT (28.3 +/- 5.8), FA (170.5 +/- 15.1), G-GT (54.3 +/- 10.7) and BT (0.76 +/- 0.09). The more 10 crystals group had higher values (AST: 82.0 +/- 29.1, ALT: 143.1 +/- 43.5, FA: 294.8 +/- 57.2, G-GT: 171.8 +/- 38.4, BT: 2.61 +/- 0.82) than in the microcrystals negative group. We concluded that in the absence of other overt causes, the presence of crystals in bile of patients with pancreatitis justifies etiology. The number is not important.
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PMID:Acute pancreatitis and microcrystals. Importance of the bile collection and biochemical parameters. 953 58

Phospholipase A2 has been suggested to be involved in the pathogenesis and pathophysiology of acute pancreatitis. We determined phospholipase A2 and amylase activities in duodenal juice collected during a secretin test from 30 consecutive patients who were suspected to have chronic pancreatitis or biliary disease. The patients underwent endoscopic retrograde cholangiopancreatography (ERCP) the following day. In the 8 patients with ERCP findings of advanced chronic pancreatitis, the mean outputs of phospholipase A2, amylase, and bicarbonate were reduced by 74%, 72%, and 60% compared to the respective values in the 13 (control) patients without a diagnosis of any pancreatic disorder or jaundice. In the 3 patients with recurrent pancreatitis but normal ERCP findings and in the 6 patients with jaundice the output values were not significantly reduced compared to those in the patients without any pancreatic disorder or jaundice. The outputs of amylase and phospholipase A2 were not significantly interrelated, whereas the outputs of phospholipase A2 and bicarbonate correlated well. Receiver characteristic (ROC) curves confirmed the high specificity and sensitivity of phospholipase A2 or bicarbonate output in patients with ERCP findings of advanced chronic pancreatitis compared to those with no changes in pancreatic ducts, with similar probability values of 0.880 +/- 0.111 (SEM), compared to the respective lower value of amylase, 0.676 +/- 0.118. Phospholipase A2 and bicarbonate output proved of equal value as markers of chronic pancreatitis and were superior to amylase output in the secretin test.
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PMID:Duodenal secretion of phospholipase A2, amylase, and bicarbonate in chronic pancreatitis. 960 59

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.
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PMID:Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome. 1039 Mar 90

Tropical calcific pancreatitis (TCP) is a chronic, nonalcoholic pancreatitis, which is limited to developing countries. In this condition, surgical decompression of the pancreatic duct consistently leads to relief of abdominal pain. However, no data are available on the effect of such intervention on pancreatic function. The aim of the present study was to prospectively evaluate b-cell and exocrine function following ductal drainage in patients with TCP. We studied 14 consecutive TCP patients who underwent ductal decompression for abdominal pain (longitudinal pancreaticojejunostomyin 12 patients, endoscopic sphincterotomy and ductal stenting in 2 subjects). Six patients who refused similar intervention served as controls. Patients were evaluated prospectively (median follow-up 13 months) for pain score, fasting and oral glucose stimulated plasma C-peptide, serum trypsin, and fecal chymotrypsin. After intervention, 1 patient died 2 months after surgery, and 2 others were lost in follow-up. The pain score improved significantly following duct decompression (median 8.0 vs. 0, p < 0.01), while in the control group there was no change in pain score (7.0 vs. 7.0). There was no change in b-cell function after intervention (fasting plasma C-peptide [mean +/- SEM] 0.41 +/- 0.08 vs. 0.42 +/- 0.05 nmol/l; peak plasma C-peptide 2.24 +/- 0.20 vs. 2.32 +/- 0.24 nmol/l). Fecal chymotrypsin was diminished in all patients prior to intervention (1.9 +/- 0.7 U/g), and did not normalize after ductal drainage in any subject. Serum trypsin levels were variable, being elevated in 29% and diminished in 47% of subjects. All 4 subjects with elevated baseline trypsin levels had a sharp fall after intervention (1020 vs. 175 ng/ml). However, serum trypsin did not normalize after ductal drainage in any patient with a diminished baseline value. In conclusion, patients with TCP have significant reduction in abdominal pain after decompression of the main pancreatic duct. However, there is no significant change in b-cell function. A fall in elevated serum trypsin suggests that there may be relief of subclinical inflammation after intervention; however, there is no improvement in exocrine function after a follow-up of 1 year.
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PMID:Prospective study of pancreatic b-cell and exocrine function following duct decompression in tropical calcific pancreatitis. 1186 45

The organotin compound di-n-butyltin dichloride (DBTC) is able to induce an acute and later a chronic pancreatitis in rats. In previous papers the authors demonstrated this DBTC pancreatitis as a rat model for an interstitial pancreatitis with tendency to transduction to the chronic form. DBTC is excreted according to its lipophilic nature by liver and bile. Therefore, the bilio-pancreatic main duct is necrotized by the tin-loaded bile. The duct system is blocked by cell debris and later by epithelial proliferations. In the chronic phase, numerous rats develop concrements in the main duct. In the present paper, the authors report about bacterial growth in some bilio-pancreatic concrements. Whereas the electron microscopic detection of tin by energy-dispersive X-ray analysis (EDX) in SEM or electron energy loss spectroscopy (EELS) in TEM was negative in the parenchyma of pancreas and liver, some concrements with bacterial cells were positive for this element. Tin mapping with energy spectroscopic imaging (ESI) in TEM demonstrated the congruency of tin signals and electron-dense particles inside these bacteria and of electron-dense accumulations in the matrix of these concrements. The low content of tin in pancreatic and liver tissue and the higher quantity of tin inside the bacterial contaminated concrements were supported by atomic absorption spectrophotometry (AAS). The paper discusses the long time preservation of tin in the concrements as an action of heavy-metal- accumulating bacteria, which should be classified in the future by bacteriological methods.
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PMID:Electron microscopic detection of tin accumulation in biliopancreatic concrements after induction of chronic pancreatitis in rats by di-n-butyltin dichloride. 1203 97

We have demonstrated that pancreatitis-associated ascitic fluid contributes to hepatocyte injury during acute pancreatitis; a phenomenon independent of ascites' enzymatic content and Kupffer cell-derived cytokines. Our aim is to characterize the mechanisms of pancreatitis-associated ascitic fluid induced hepatocyte death. NIH mice were injected intraperitoneally with pathogen-free pancreatitis-associated ascitic fluid. Twenty-four hours later, serum AST, ALT, LDH, and hepatocyte apoptosis (TUNEL) were measured. Human hepatocytes (CCL-13) were treated with pancreatitis-associated ascitic fluid +/-SB203580 or caspase-3 inhibitor-II. Mitochondrial membrane integrity was determined by DiOC6 staining. Apoptosis was measured by TUNEL staining and flow cytometry after dual labeling with Annexin-V/7-AAD. Data are mean +/- SEM of triplicates. Pancreatitis-associated ascitic fluid increased serum AST, ALT, LDH, and apoptotic cells in the mouse liver (all P < 0.03 vs. sham). In CCL-13 cells, pancreatitis-associated ascitic fluid induced a time and dose-dependent increase in apoptosis, in addition to p38-MAPK phosphorylation (P = 0.02 vs. control), caspase-3 cleavage (P < 0.03 vs. control) and decreased DiOC6 mitochondrial staining (P < 0.01 vs. control). Both caspase-3 inhibitor-II and SB203580 decreased apoptosis, but the former had no effect on DiOC6 staining. Pancreatitis-associated ascitic fluid induces liver injury and hepatocyte apoptosis by activating p38-MAPK and caspase-3 dependent pro-apoptotic pathways.
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PMID:Liver injury during acute pancreatitis: the role of pancreatitis-associated ascitic fluid (PAAF), p38-MAPK, and caspase-3 in inducing hepatocyte apoptosis. 1260 Apr 44

Mechanisms of pain transduction in acute pancreatitis are poorly understood. Increased Fos expression in the spinal cord is a marker of activation of nociceptive neurons. We hypothesized that cerulein pancreatitis leads to increased Fos expression at T9 and T10, which receive sensory input from the pancreas. Rats were injected with cerulein (100 microg/kg, s.c.) or saline carrier (NS). Endpoints at 4, 6, and 10 h were serum amylase, myeloperoxidase activity (MPO), and spinal cord Fos expression (number of immunoreactive nuclei/section dorsal gray matter). Fos-like immunoreactivity (FLI) at T9-T10 was compared to internal controls (T6, T12). An average of 20 spinal cord histologic sections were evaluated per rat. Some animals were injected with the mu-opioid receptor agonist, buprenorphine (90 microg/kg, s.c.), 3 h after cerulein, and their endpoints were measured at 6 h. Analysis of variance and t tests were used for statistical analysis. Results are means +/- SEM. As expected, cerulein induced edematous pancreatitis, with a 4-fold increase in serum amylase at 6 h [cer (n = 8): 14,000 +/- 1,300 U/ml versus NS (n = 10): 3,700 +/- 300, P < 0.005)] and a 2-fold increase in MPO activity (0.25 +/- 0.05) activity units/dry wt versus 0.13 +/- 0.02, P < 0.05). Cerulein induced nearly a 2-fold increase in FLI at T9 and T10 [n = 10 (cer) and n = 13 (NS): T9, 14 +/- 1.5 versus 7.8 +/- 0.88; T10, 15 +/- 1.7 versus 8.3 +/- 0.70; P < 0.05]. Peak effects of cerulein on FLI occurred at 6 h and were greatest at T9/T10 with relative sparing of T6/T12. T6/T12 expression was similar in experimental and control groups. Buprenorphine significantly reduced both serum amylase and FLI and T9/T10. Cerulein-induced acute pancreatitis in rat increases visceral nociceptive signaling at spinal cord levels T9 and T10, with a peak at 6 h. Blockade of this effect by the mu-opioid receptor agonist buprenorphine could occur either by direct activation of central opioid receptors and/or an anti-inflammatory mechanism. FLI is a useful tool for studying the pathophysiology of pain in experimental acute pancreatitis.
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PMID:Activation of nociceptive neurons in T9 and T10 in cerulein pancreatitis. 1504 23

Intercurrent illness and episodes of hospitalization and surgery are common in an aging population, who, at the same time, are experiencing age-related bone loss. The objective was to test the hypotheses (1) that intercurrent illness severe enough to require hospitalization produces clinically important bone loss, and (2) that antiresorptive therapy will reduce that loss. The study was a retrospective analysis of bone mineral density (BMD) change at hip and spine in subjects of the risedronate postmenopausal osteoporosis phase III trials experiencing serious adverse events (SAEs). Subjects were 243 hospitalized for non-skin cancers, pneumonia, myocardial infarction, cerebrovascular accident, gallbladder disease, and pancreatitis, on whom BMD data were available both before and after the SAE; and 286 non-hospitalized control subjects matched to those with SAEs by age, height, weight, prevalent fracture, and visit interval. In hospitalized, placebo-treated participants, the annualized percent change in BMD (mean+/-SEM) across the period of hospitalization was -0.65+/-0.39 at lumbar spine, -1.13+/-0.55 at femoral neck, and -2.66+/-0.58 at femoral trochanter; the corresponding values for the non-hospitalized, placebo controls were +0.46+/-0.28, -0.77+/-0.34, and -0.67+/-0.34. These values were more negative at all three sites for the hospitalized subjects, and significantly so at lumbar spine and femoral trochanter (P=0.019 and 0.002, respectively). By contrast, in the risedronate-treated participants, all sites exhibited bone gain and there was no significant difference between hospitalized and non-hospitalized participants. Intercurrent illness resulting in hospitalization produced a rapid bone loss across the period of illness comparable in magnitude to documented age-related loss. Risedronate in a dose of 5 mg/day effectively abolished this loss.
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PMID:Hospitalization-related bone loss and the protective effect of risedronate. 1613 44

Use of parenteral pentavalent antimonials to treat leishmaniasis is associated with a range of cardiological, biochemical and haematological adverse effects. The most serious of these is the development of ventricular tachyarrhythmias associated with prolongation of the electrocardiographic rate-corrected QT interval (QTc). Whereas some studies have reported that serious cardiological and biochemical adverse effects are common and often require treatment interruption or discontinuation, others have reported the drugs to be well tolerated. We conducted a detailed retrospective analysis of adverse events among British returned travellers (n=65) with New World cutaneous or mucosal leishmaniasis who received i.v. sodium stibogluconate (SbV) for >or=21 days. The mean+/-SEM QTc progressively increased from 389+/-3.1 msec to 404+/-2.9 msec during 3 weeks of treatment and the QTc reached the threshold for potential cardiac toxicity among 6 (10%) patients during the third week of treatment. Marked QTc prolongation and ventricular tachyarrhythmias occurred in one elderly patient with hypokalaemia and pre-existing cardiovascular morbidity. Although increased serum concentrations of amylase and hepatic transaminases were observed among 67% and 85% of patients respectively, none developed clinical pancreatitis or hepatitis and treatment modification was not required. SbV can be used safely in this population with adequate monitoring and the need for treatment interruption is uncommon. Identification of factors before and during treatment that may increase the risk of QTc prolongation and arrhythmias is important.
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PMID:Electrocardiographic and biochemical adverse effects of sodium stibogluconate during treatment of cutaneous and mucosal leishmaniasis among returned travellers. 1628 67


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