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)

Cerulein-induced acute pancreatitis in rats is associated with a reversible lung injury that is characterized by alveolar capillary endothelial-cell injury, increased microvascular permeability, interstitial edema formation, and intraalveolar hemorrhage and fibrin deposition. The role of mediators in this injury was analyzed using gravimetric data, microvascular permeability indices, electron microscopy, and a quantitative morphometric analysis. Neutrophil depletion induced by a specific antibody was highly protective against lung injury. Interruption of the complement pathway (using low dose Naja naja cobra venom factor) also protected against lung injury. Catalase and superoxide dismutase were also protective. The iron chelator deferoxamine and the hydroxyl radical scavenger, dimethylsulfoxide, were not protective against acute lung injury. These data suggest that complement, neutrophils, and neutrophil-derived (H2O2-dependent) oxygen products mediate lung injury that occurs secondary to cerulein-induced pancreatitis. In contrast to other models of neutrophil-dependent, oxygen-radical-mediated lung injury, this lung injury does not appear to be an iron-dependent and hydroxyl-radical mediated injury. We postulate that the process of acute pancreatitis leads to complement activation followed by neutrophil recruitment, sequestration, and adherence to alveolar capillary endothelial cells. Ultimately lung injury appears to result from local endothelial-cell injury secondary to neutrophil-generated oxygen products that may be myeloperoxidase dependent.
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PMID:Neutrophil-dependent, oxygen-radical mediated lung injury associated with acute pancreatitis. 258 87

Oxygen-derived free radicals have been implicated in the pathogenesis of acute pancreatitis, yet adaptive responses in the pancreas in vivo to oxidative stress remain poorly defined. We have investigated expression of the stress protein heme oxygenase in the intact pancreas of rats with caerulein-induced pancreatitis and in cultured pancreatic acinar and islet cell lines. Expression of inducible heme oxygenase-1 (HO-1) in the pancreas in vivo was enhanced 12-24 h after induction of pancreatitis. In murine islet (betaTC3) and rat acinar (AR42J) pancreatic cells, H2O2, methyl viologen, cadmium chloride and diethylmaleate enhanced HO-1 expression in a dose- and time-dependent manner, without altering expression of constitutive HO-2. Enhanced expression of HO-1 in the pancreas in vivo and pancreatic islet and acinar cells may contribute to cellular defences against oxidative stress associated with acute pancreatitis.
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PMID:Expression of stress proteins heme oxygenase-1 and -2 in acute pancreatitis and pancreatic islet betaTC3 and acinar AR42J cells. 908 94

The important role of oxygen radicals in acute experimental pancreatitis was demonstrated by study of the changes in the antioxidant system in the blood, liver, kidney, and pancreas of rats after the administration of a large quantity of L-arginine (L-Arg). The changes in lipid peroxidation and in reduced and oxidized glutathione were followed, as well as the activities of peroxide-decomposing enzymes (glutathione peroxidase and catalase) and H2O2-producing superoxide dismutases. The results demonstrated that "oxidative stress" develops and acute pancreatitis appears rapidly after L-Arg treatment. Oxidative stress symptoms are expressed 24 h after the final treatment. Slow restitution of the studied antioxidant system can be demonstrated as early as after 48 h.
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PMID:Oxidative stress changes in L-arginine-induced pancreatitis in rats. 916 81

Molecular mechanisms associated with apoptosis in pancreas remain largely unknown. Clusterin mRNA is induced in several tissues in response to most apoptotic stimuli. In these tissues, clusterin has an antiapoptotic activity. The aim of this work was to test whether clusterin, which is not expressed in normal pancreas, was induced in pancreas during pancreatitis and pancreatic development. Clusterin mRNA levels were strongly increased 6 h after pancreatitis induction. Maximal expression happened between 24-48 h and decreased progressively to undetectable levels at day 5. Clusterin mRNA was expressed with similar intensity in oedematous caerulein-induced pancreatitis and in response to various degrees of necrohaemorrhagic taurocholate-induced pancreatitis, indicating a maximal gene activity in all types of pancreatitis; in situ hybridization showed that the acinar cells and some ducts expressed clusterin mRNA. A single band of about 35-38 kDa was detected by western blot in pancreatic homogenates and in pancreatic juice from rats with acute pancreatitis, but not from control rats. Clusterin mRNA expression was strong in late fetal life and remains high until day 11 post-partum, then decreased progressively with a minimum from 35 to 90 days post-partum. Clusterin mRNA levels were strongly induced in pancreatic acinar AR4-2J cells in response to various apoptotic stimuli (i.e., cycloheximide, staurosporine, ceramide and H2O2) but not with interleukin (IL)-1, IL-4 or IL-6 or heat shock, which do not induce apoptosis in AR4-2J cells. In conclusion, we demonstrated that clusterin is synthesized and released by the pancreas. Its strong expression during acute pancreatitis suggests its involvement in the pancreatic response to injury. Clusterin is also induced during pancreatic development. Because these situations are associated with apoptosis and clusterin was shown to protect against apoptosis, we speculate that clusterin could be involved in the control of acinar cell apoptosis.
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PMID:Clusterin overexpression in rat pancreas during the acute phase of pancreatitis and pancreatic development. 966 Jan 81

The important role of oxygen radicals in acute experimental pancreatitis was demonstrated by study of the changes in the antioxidant system in the blood, liver, kidney and pancreas of rats after the administration of a large quantity of L-arginine (L-Arg). The changes in lipid peroxidation and in reduced and oxidized glutathione were followed as well as the activities of peroxide-decomposing enzymes (glutathione peroxidase and catalase) and H2O2-producing superoxide dismutases. The results demonstrated that acute pancreatitis and "oxidative stress" develop rapidly after L-Arg treatment. "Oxidative stress" symptoms are expressed 24 hours after the final treatment. Slow restitution of the studied antioxidant system can be demonstrated as early as after 48 hours.
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PMID:Lipid peroxidation and antioxidant system changes in acute L-arginine pancreatitis in rats. 970 7

1. Cypridina luciferin analogues, 2-methyl-6-(p-methoxyphenyl)-3,7- dihydroimidazo[1,2-a]pyrazin-3-one (MCLD) and 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2-a]pyrazin-3-one(CLA ), react with O2- or 1O2 to emit light in visible region. Such chemiluminescences were used for the detection of O2- or 1O2 in activated leukocyte systems and myeloperoxidase (granulocyte-extract) + Br- + H2O2 systems in vitro. 2. The mechanisms of MCLA (CLA)-dependent luminescence is described in detail. Superoxide generated from sinusoidal cells in acute ethanol intoxication of rats was detected by MCLA-dependent luminescence from the surface of perfused rat liver (organ luminescence). 3. Furthermore, with alive animals, O2- generated in the lung of rats with necrotized pancreatitis and that in the stomach of rats after ischemia/reperfusion were detected by their organ luminescences.
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PMID:Detection of active oxygen species in biological systems. 987 66

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-KB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). ROS generation in neutrophils increased by PMA, which was inhibited by NAC and SOD. The productions of H2O2, LPO and TNF-alpha were increased with the amounts of PMA-primed neutrophils added to acinar cells while the productions of H2O2, LPO and cytokines increased with time. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-KB and decreasing cytokine production.
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PMID:NF-kappaB and cytokines in pancreatic acinar cells. 1098 15

Recent studies demonstrate that reactive oxygen species (ROS) are important mediators of acute pancreatitis, whether induced experimentally or in necrotizing pancreatitis in humans; however, the cellular processes involved remain unclear. Adapter protein CrkII, plays a central role for convergence of cellular signals from different stimuli. Cholecystokinin (CCK), which induces pancreatitis, stimulates CrkII tyrosine phosphorylation and CrkII protein complexes, raising the possibility it can be important in the acinar cell responses to ROS. Therefore, our aim was to investigate whether CrkII signaling is involved in the biological response of rat pancreatic acini to H2O2 and the intracellular mediators implicated. Treatment of isolated rat pancreatic acini with H2O2 rapidly stimulates CrkII phosphorylation, measured as electrophoretic mobility shift and by using a phosphospecific antibody (pTyr221). Tyrosine kinase blocker B44 inhibits the higher phosphorylation state, demonstrating that it occurs mainly in tyrosine residues. H2O2-induced CrkII phosphorylation is time- and concentration-dependent, showing maximal effect with 3 mM H2O2 at 5 min. The intracellular pathways induced by H2O2 leading to CrkII tyrosine phosphorylation do not involve PKC, intracellular calcium, PI3-K or the actin cytoskeleton integrity. ROS generation clearly promotes the formation of protein complex CrkII-PYK2. In conclusion, ROS clearly affect the key adapter protein CrkII signaling by two ways: stimulation of CkII phosphorylation and a functional consequence: formation of CrkII-protein complexes. Because of its central role in activating more distal pathways, CrkII might likely play an important role in the ability of ROS to induce pancreatic cellular injury and pancreatitis.
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PMID:Adapter protein CRKII signaling is involved in the rat pancreatic acini response to reactive oxygen species. 1618

Hydrogen peroxide (H2O2) has been reported to be an effective radiation sensitizer for various cancers. A combination therapy comprising fine-needle injection (FNI) of H2O2 under endoscopic ultrasound (EUS) guidance and chemoradiation might improve treatment outcomes of pancreatic cancer; however, there have been no reports thus far. The aims of this study were to evaluate the feasibility and safety of EUS-FNI of H2O2 into the pancreas using a porcine survival model. EUS-FNI was performed in the pancreas of six pigs, which were randomly divided into three groups based on the solution injected: group 1, 2 mL of sodium hyaluronate (control); group 2, 0.5 mL of H2O2; group 3, 2 mL of H2O2. To evaluate any adverse events, blood tests and computed tomography (CT) were performed before and after FNI, as well as days 3 and 7 subsequently. The pigs were necropsied on day 7. Histologic evaluation was performed according to the criteria for experimental acute pancreatitis. EUS-FNI was successful in all pigs. CT immediately after FNI revealed gas formation in the FNI area in groups 2 and 3. No adverse events were revealed by blood tests and CT. Histologic evaluations revealed pancreatitis scores of 5 and 5 in group 1, 7 and 7 in group 2 and 14 and 15 in group 3. EUS-FNI of H2O2 into the pancreas is feasible; however, it could cause pancreatitis. FNI of H2O2 into only the pancreatic tumor might be ideal in minimizing possible adverse events.
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PMID:Endoscopic Ultrasound-Guided Fine-Needle Injection of Hydrogen Peroxide into the Pancreas: Feasibility and Tolerability Study Using a Survival Porcine Model. 3055 84