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)

Examination of immunological status in patients with acute destructive pancreatitis with uncomplicated (14 patients) and complicated (infectious-inflammatory processes--18 patients) postoperative period illustrated depression of T- and B-links of immunity, reduction of absolute and relative number of TFU- and TFC-lymphocytes. All the patients demonstrated reliable elevation of phagocytic rate, phagocytic index and number of circulating immune complexes. These changes were more significant in patients with complicated postoperative period. Level of lactoferrin in patients with complicated period was by 10% higher than in patients without complications. Significant elevation of tumor necrosis factor Ia in blood was registered in patients of both groups. During all the periods of examination the level of interleukin-8 was higher in patients with complicated postoperative period than in the patients with favorable postoperative period. This interleukin-8 is a reliable marker of postoperative complications in acute destructive pancreatitis.
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PMID:[Characteristics of immunologic disorders in patients with acute destructive pancreatitis]. 1149 Apr 88

Nuclear matrix protein (NMP) is an index of apoptosis. We measured NMP in 22 patients with acute pancreatitis and investigated the relationship between severity and NMP. We also measured tumor necrosis factor-alpha (TNF-alpha) and investigated the relationship between NMP and TNF-alpha. The NMP value increased significantly as the pancreatitis became more increasingly severe, and the NMP values were significantly higher in the group with multiple organ dysfunction syndrome (MODS) than in the group without MODS. A comparison of the NMP values in the group that survived and the group that died revealed higher NMP values in the former. A significant correlation was found between the NMP values and the TNF-alpha values, suggesting that apoptosis may contribute to the pathophysiology of acute pancreatitis.
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PMID:Nuclear matrix protein (NMP) levels in patients with acute pancreatitis. 1150 25

AIM:To investigate the role of tumor necrosis factor (TNF) in lung injury during acute necrotizing pancreatitis (ANP), and the therapeutic effect of Tong Xia purgative method in minimizing the severity of lung injury.METHODS:Fourteen canines were randomly divided into 3 groups:the Tong Xia treatment group (n = 5) using Dachengqitang; saline control group (n = 5), and the sham operation group (n =4). TNF activity in serum and in bronchoalveolar lavage fluid (BALF), the serum endotoxin levels were measured,and the severity of lung injury evaluated.RESULTS:Elevation of TNF activity was more prominent in BALF than in serum. TNF activity in serum at 6 and 12 hours and in BALF was significantly decreased in the Tong Xia treatment group than in the saline control one (q = 21.11, q = 12.07, q = 9.03, respectively, P <0.01) and the lung injury was significantly alleviated at 12 hours as compared with that in the saline group, manifested as amelioration of the lung wet/dry weight ratio, decrease in protein concentration and neutrophils count in BALF, and improvement of pulmonary inflammatory changes. A positive correlation was demonstrated between serum TNF activity and endotoxin level.CONCLUSION:Hypersecretion of TNF is shown to be one of the major causes of lung injury during ANP; Tong Xia purgative method could alleviate the degree of lung injury mediated by TNF.
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PMID:Experimental study of Tong Xia purgative method in ameliorating lung injury in acute necrotizing pancreatitis. 1181 36

Liver injury is a manifestation of the systemic inflammatory response during acute pancreatitis. We have demonstrated that elastase induces macrophage tumor necrosis factor (TNF) production in distant organs, thus mimicking pancreatitis-associated organ injury. The aim of this study was to determine the mechanism by which elastase induces hepatic cytokine production. Rat livers (n = 40) were perfused with elastase +/- gadolinium (Gd) to inhibit Kupffer cells. Liver parenchymal enzymes and TNF were measured in the effluent. In vitro, rat hepatocytes or Kupffer cells were treated with elastase (1 U/ml) +/- Gd (0.5 mg/ml) or pyrrolidine dithiocarbamate (PDTC; 0.5 mg/ml). TNF protein, TNF messenger RNA, and NF-kappa B activation were determined. In vivo, Gd blunted the elastase-induced TNF production and decreased AST, ALT, LDH, and nonviable cells (propidium iodide) (P < or= 0.03 vs. elastase). In vitro, elastase induced TNF production from Kupffer cells (P < 0.001 vs. control) but not from hepatocytes. Gd or PDTC significantly attenuated the elastase-induced TNF production (P < 0.001). Elastase-induced overexpression of TNF messengerRNA and activation of NF-kappa B was attenuated by Gd. Pancreatic elastase induces a pattern of liver injury similar to that seen during acute pancreatitis by activating cytokine production and gene expression within Kupffer cells via NF-kappa B. Gd exhibits a protective effect against elastase-induced liver injury by inhibiting activation of NF-kappa B.
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PMID:Pancreatic elastase induces liver injury by activating cytokine production within Kupffer cells via nuclear factor-Kappa B. 1202 2

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

Adenosine protects against cellular damage and dysfunction under several adverse conditions including inflammation and ischemia. In this study, we examined the effects of 3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride (KF24345), an adenosine uptake inhibitor, on experimental acute pancreatitis induced by choline-deficient and ethionine-supplemented diet in mice. KF24345, administered with the diet onset and every 24 h thereafter, prevented hyperamylasemia, acinar cell injury and serum tumor necrosis factor-alpha elevation and ultimately decreased mortality. Therapeutic treatment with KF24345, which started 32 h after the diet onset, also decreased mortality. The beneficial effect of KF24345 on mortality was abolished by the pretreatment with 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385), a selective adenosine A(2A) receptor antagonist. An intravenous injection of KF24345 at 48 h after the diet onset increased plasma adenosine concentrations in mice with acute pancreatitis. These results suggest that KF24345 shows anti-pancreatitis effects via endogenous adenosine and adenosine A(2A) receptors. The adenosine uptake inhibition could be a new therapeutic approach for acute pancreatitis.
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PMID:KF24345, an adenosine uptake inhibitor, ameliorates the severity and mortality of lethal acute pancreatitis via endogenous adenosine in mice. 1240 9

Efforts to unravel the events in the evolution of tissue damage in acute pancreatitis have shown a number of inflammatory mediators to be involved. The pathways of damage are similar, whatever the etiology of pancreatitis, with three phases of progression: local acinar injury, systemic response, and generalized sepsis. The proinflammatory response is countered by an anti-inflammatory response, and an imbalance between these two systems leads to localized tissue destruction and distant organ damage. Cytokines lie at the heart of the problem and are involved in all aspects of the cascade leading to systemic inflammatory response syndrome and multiple organ dysfunction syndrome. This review discusses the present knowledge about the role of various mediators in this process, their genetic control, and the effects of their modulation. The major proinflammatory mediators are tumor necrosis factor, interleukins 1, 6, and 8, platelet activation factor, and the chemokines. The major anti-inflammatory factors include interleukin 10, and interleukin 1 receptor antagonist. Emerging knowledge of new mediators as well as future strategy of damage control is discussed.
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PMID:Cytokine storm in acute pancreatitis. 1248 60

We have demonstrated that Kupffer cell-derived tumor necrosis factor (TNF) mediates pancreatitis-associated liver injury. The aim of this study was to determine the role of p38 mitogen-activated protein kinase (MAPK), extracellular stress-related kinase 1/2 (ERK1/2), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and nuclear factor-kappaB (NF-kappaB) in TNF gene expression within Kupffer cells. TNF and TNF-mRNA were measured in rat livers perfused with elastase. TNF, TNF-mRNA, NF-kappaB activation, and phosphorylated p38-MAPK, SAPK/JNK, and ERK1/2 were determined in Kupffer cells treated with elastase. Elastase increased TNF and upregulated TNF-mRNA in livers (P<0.03) and Kupffer cells (P<0.001). Phosphorylated p38-MAPK, SAPK/JNK, and ERK1/2 and activated NF-kappaB were detected in Kupffer cells at 7 minutes; at 60 minutes, TNF-mRNA peaked and NF-kappaB returned to baseline, whereas all three kinases remained activated. Gadolinium inhibited elastase-induced upregulation of TNF-mRNA (P < 0.001), TNF production (P<0.001), and attenuated SAPK/JNK, as well as ERK1/2, but not p38-MAPK. Both UO126 and SB203580 significantly inhibited elastase-induced upregulation of TNF-mRNA and TNF production (P<0.001), but only UO126 inhibited activation of NF-kappaB. It was concluded that pretranscriptional regulation of TNF gene expression in Kupffer cells follows an orderly activation of p38-MAPK, ERK1/2, and SAPK/JNK that may not converge on NF-kappaB. The seemingly limited duration of NF-kappaB activation may be important in "switching off" the cytokine cascade during acute pancreatitis.
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PMID:Regulation of Kupffer cell TNF gene expression during experimental acute pancreatitis: the role of p38-MAPK, ERK1/2, SAPK/JNK, and NF-kappaB. 1255 81

Glucocorticoids are potent anti-inflammatory drugs. The molecular mechanisms underlying these effects have not yet been fully revealed. The aim of the present study was to establish whether methylprednisolone pretreatment is beneficial and if it can block the pancreatic DNA binding of the transcription factor nuclear factor-kappaB (NF-kappaB) and proinflammatory cytokine synthesis during cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. Additionally, we set out to investigate the potential effects of methylprednisolone and CCK on pancreatic heat shock protein (HSP) synthesis. The dose-response (5-40 mg/kg) and time-course (6-72 h) curves of methylprednisolone on pancreatic HSP60 and HSP72 synthesis were evaluated following methylprednisolone treatment. We demonstrated that methylprednisolone specifically and dose-dependently induced HSP72 in the pancreas of rats, while it did not have a significant effect on HSP60 expression. The pancreatitis was induced near the peak level of HSP72 synthesis (2 x 30 mg/kg body weight [b.w.] methylprednisolone i.m. at an interval of 12 h, followed by a 12-h recovery period after the second injection of methylprednisolone) by administering 2 x 100 microg/kg CCK subcutaneously at an interval of 1 h. The injections of CCK in the vehicle-pretreated group significantly elevated the levels of pancreatic HSP60 and HSP72 2-4 h after the second CCK injection. Methylprednisolone pretreatment ameliorated many of the examined laboratory (the pancreatic weight/body weight [p.w./b.w.] ratio, the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic levels of tumor necrosis factor-alpha and interleukin-6, the degree of lipid peroxidation, protein oxidation, nonprotein sulfhydryl group content and the pancreatic myeloperoxidase activity) and morphological parameters of the disease. Methylprednisolone pretreatment did not influence pancreatic NF-kappaB DNA binding, but decreased proinflammatory cytokine synthesis in this acute pancreatitis model. The findings suggest that the anti-inflammatory effect of large doses of methylprednisolone in secretagogue-induced pancreatitis occurs downstream of NF-kappaB DNA binding, and that increased pancreatic HSP72 synthesis may play a role in the protective effect of the drug.
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PMID:The anti-inflammatory effect of methylprednisolone occurs down-stream of nuclear factor-kappaB DNA binding in acute pancreatitis. 1262 May 16

Increased lipid peroxidation, enhanced nuclear factor kappa-B (NF-kappaB) activation and augmented tumor necrosis factor-alpha (TNF-alpha) production have been implicated in cerulein-induced pancreatitis. We investigated whether lipid peroxidation inhibition might reduce NF-kappaB activation and the inflammatory response in cerulein-induced pancreatitis. Male Sprague-Dawley rats of 230-250g body weight received administration of cerulein (80 microg/kg s.c. for each of four injections at hourly intervals). A control group received four s.c. injections of 0.9% saline at hourly intervals. Animals were randomized to receive either raxofelast, an inhibitor of lipid peroxidation (20 mg/kg i.p. administered with the first cerulein injection) or its vehicle (1 ml/kg of a 10% DMSO/NaCl solution). All these rats were sacrificed 2 h after the last injection of either cerulein or its vehicle. Raxofelast administration (20 mg/kg i.p. with the first cerulein) significantly reduced malondialdehyde (MDA) levels, an index of lipid peroxidation (CER + DMSO = 3.075 +/- 0.54 micromol/g; CER + raxofelast = 0.693 +/- 0.18 micromol/g; p < 0.001), decreased myeloperoxidase (MPO) activity (CER + DMSO = 22.2 +/- 3.54 mU/g; CER + raxofelast = 9.07 +/- 2.05 mU/g, p < 0.01), increased glutathione levels (GSH) (CER + DMSO = 5.21 +/- 1.79 micromol/g; CER + raxofelast = 15.71 +/- 2.14 micronol/g; p < 0.001), and reduced acinar cell damage evaluated by means of histology and serum levels of both amylase (CER + DMSO = 4063 +/- 707.9 U/l; CER + raxofelast = 1198 +/- 214.4 U/l; p < 0.001), and lipase (CER + DMSO = 1654 +/- 330 U/l; CER + raxofelast = 386 +/- 118.2 U/l; p < 0.001), Furthermore, raxofelast reduced pancreatic NF-kappaB activation and the TNF-alpha mRNA levels and tissue content of mature protein in the pancreas. Indeed, lipid peroxidation inhibition might be considered a potential therapeutic approach to prevent the severe damage in acute pancreatitis.
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PMID:Lipid peroxidation inhibition reduces NF-kappaB activation and attenuates cerulein-induced pancreatitis. 1274 37


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