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)

Valproic acid is a widely used drug in the treatment of epilepsy and, compared to other anticonvulsant drugs, is considered safe. The most common side effects of valproic acid ingestion or therapy are transient nausea, vomiting, abdominal cramps, and diarrhea. Most of these complaints are mild. However, more serious adverse reactions can occur such as hepatotoxicity and pancreatitis. It has been proposed that, whenever possible, valproic acid not be used in the younger child, the child with a severe seizure disorder or other neurological disorders, mental retardation, developmental delay, organic brain disease, congenital abnormalities, or the child who is taking multiple anticonvulsant drugs, as these factors may increase the likelihood of hepatotoxicity and/or pancreatitis. In the present report, we describe a fatal case of acute hemorrhagic pancreatitis in a four and a half-year-old Hispanic female child who was receiving valproic acid in combination with another anticonvulsant drug for control of focal seizures. The patient also received the macrolide antibiotic azithromycin. For pediatricians and forensic pathologists valproic acid-induced pancreatitis can be a challenging diagnosis which must not be mistaken for abdominal trauma. We discuss the workup of the patient and differential diagnosis.
Pediatr Pathol Mol Med
PMID:Pathological case of the month: sudden death in a child as a result of pancreatitis during valproic acid therapy. 1239 3

Enzyme load in pancreas has been considered a risk factor in the development of acute pancreatitis. In order to confirm this hypothesis our aim was to analyze the development and evolution of acute pancreatitis (AP) induced by bile-pancreatic duct obstruction (BPDO) after reducing the pancreatic enzyme content. L-364,718 - a potent CCK-receptor antagonist - was administered (0.1 mg/kg/day) for 7 days before inducing AP by BPDO. The course of AP was evaluated at different times from 1.5-48 h after BPDO. Amylase and trypsinogen contents and cytosolic calcium levels were measured by flow cytometry using specific antisera against pancreatic enzymes labelled with isothiocyanate of fluorescein and Fluo 3, respectively. The severity of the disease at the different stages was evaluated by measurements of amylase activity in ascites and plasma, percentage of pancreatic fluid and haematocrit. Electron microscopy study of the pancreas showed an increased number of zymogen granules spread through the acinar cells of control rats treated with L-364,718 for 7 days, however, total enzyme content in individual acinar cells was significantly (p < 0.01) diminished. AP significantly increased intracellular amylase and trypsinogen load from 3-12 h after BPDO, and prior L-364,718 treatment enhanced the blockade of enzyme secretion. As a result, acinar enzyme content was significantly increased from earlier stages (1.5 h after BPDO). In parallel, increased cytosolic calcium levels observed up to 24 h after BPDO appeared earlier in L-364,718-treated rats than in those not treated. The severity of AP seems to have been higher in rats previously treated with the CCK-receptor antagonist as indicated by the significantly higher pancreatic fluid and amylase activity in ascites and plasma observed at different times after BPDO. Our results indicate that there is no correlation between the severity of pancreatitis and the amount of enzymes accumulated in the pancreas before the disease is induced.
Mol Cell Biochem 2002 Nov
PMID:Low enzyme content in the pancreas does not reduce the severity of acute pancreatitis induced by bile-pancreatic duct obstruction. 1248 74

The regenerative process of the pancreas after acute pancreatitis (AP) is characterized by acinar and ductal cell proliferation with synthesis and transient deposition of extracellular matrices. Various growth factors were reported to be highly expressed in AP, but their regulation has not yet been clarified. Fibroblast growth factor (FGF)-7, also known as keratinocyte growth factor (KGF), and FGF-10 are members of the FGF family and show high structural homology and similar biological characteristics. Both are mainly synthesized by mesenchymal cells and stimulate epithelial cells via KGF receptor (KGFR) which is a splice variant of FGFR-2. In the present study, we attempted to immunohistochemically determine the localization of FGF-7 and FGF-10 in pancreatic tissues of an L-arginine-induced rat pancreatitis model. Furthermore, highly specific KGFR antibodies were prepared and used for Western blot analysis and immunohistochemistry. In the normal pancreas, FGF-7 was localized in alpha cells of islets, but FGF-10 was not detected. KGFR was also localized in islet cells, ductal cells, and centroacinar cells in the normal pancreas. In the pancreatic tissues of rats with L-arginine-induced pancreatitis, FGF-7 was localized in alpha cells, whereas FGF-10 was expressed in vascular smooth muscle cells (VSMCs). KGFR was not expressed in centroacinar cells and its level decreased after L-arginine treatment. However, KGFR was detected instead in some acinar cells and VSMCs in addition to islet cells. These findings suggest that FGF-7 and FGF-10 contribute to the regeneration and differentiation of acinar cells and angiogenesis in AP through KGFR.
Exp Mol Pathol 2002 Dec
PMID:Differential distribution of fibroblast growth factor (FGF)-7 and FGF-10 in L-arginine-induced acute pancreatitis. 1256 93

Several genetic factors have been well known to predispose one to chronic pancreatitis (CP). However, little is known about the genetic factors that may provide a protective effect against the disease. Having found a nonsense mutation (c.111C>A; Y37X) and a splicing mutation (IVS2+1G>A) in the cationic trypsinogen gene (protease, serine, 1; PRSS1) in alcoholics without the development of CP, but not in alcoholics with CP and patients with hereditary or idiopathic CP, we propose that while "gain of function" mutations in the PRSS1 gene predispose one to pancreatitis, "loss of function" mutations in the gene may protect one against the disease.
Mol Genet Metab 2003 May
PMID:"Loss of function" mutations in the cationic trypsinogen gene (PRSS1) may act as a protective factor against pancreatitis. 1276 48

Recent studies suggest that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical acute pancreatitis. In the present study, we investigated the effects of the free radical scavenger edaravone, which is used clinically as an anti-stroke agent, in the development of experimental closed duodenal loop (CDL)-induced acute pancreatitis. In the CDL-pancreatitis model, after edaravone and vehicle saline were injected intravenously, pancreatitis was induced for 7 h by the CDL technique. The subsequent ascites volume, wet pancreatic weight, serum amylase levels, and pancreatic tissue lipid peroxide levels were evaluated. Pancreatic tissue damage was also evaluated histologically. In this CDL-induced pancreatitis model, edaravone treatment tended to reduce the ascites volume and inhibit the increases in the wet pancreatic weight. Edaravone also tended to reduced the microscopic mucosal damage scores and pancreatic tissue lipid peroxide levels. In particular, the serum amylase levels in the edaravone-treated rats (1-20 mg/kg i.v.) were significantly reduced as compared to the vehicle-treated rats. These results strongly support the involvement of ROS in the pathogenesis of CDL-induced acute pancreatitis and cytoprotective effects of free radical scavender against pancreatic acinar cells. A clinical effect for edaravone against acute pancreatitis is strongly expected.
Int J Mol Med 2003 Jul
PMID:The free radical scavenger edaravone suppresses experimental closed duodenal loop-induced acute pancreatitis in rats. 1279 21

To test the hypothesis that endotoxin is absorbed from the gut into the circulation in rats with experimental acute pancreatitis we studied two different animal models. In the first model necrotizing pancreatitis was induced by the ligation of the distal bilio-pancreatic duct while in the second, experimental oedematous acute pancreatitis was induced by subcutaneous injections of caerulein. In both experiments, in the colon of rats with acute pancreatitis endotoxin from Salmonella abortus equi was injected. Endotoxin was detected by immunohistochemistry in peripheral organs with specific antibodies. The endotoxin was found only in rats with both acute pancreatitis and endotoxin injected into the colon and not in the control groups. The distribution of endotoxin in liver at 3 and 5 days was predominantly at hepatocytes level around terminal hepatic venules, while in lung a scattered diffuse pattern at the level of alveolar macrophages was identified. A positive staining was observed after 12 hours in the liver, lung, colon and mesenteric lymph nodes of rats with both caerulein pancreatitis and endotoxin injected into the colon. We conclude that the experimental acute pancreatitis leads to early endotoxin translocation from the gut lumen in the intestinal wall and consequent access of gut-derived endotoxin to the mesenteric lymph nodes, liver and lung.
J Cell Mol Med
PMID:Endotoxin translocation in two models of experimental acute pancreatitis. 1475 10

Polymorphonuclear cells (PMN) activation is an essential step in acute pancreatitis (AP). We investigated the activation status of PMN, oxidative stress and pancreatic damage in early stage of experimental ceruleine pancreatitis in rats. The PMN action was modulated by monoclonal antibody CD 11b administration. The circulating WBC and polymorphonuclear cells count was reduced after AP induction. Chemiluminescence of whole blood PMN was remarkably reduced in AP group and increased after MoAb CD 11b administration. The CD 11b blockade significantly reduced the WBC infiltration and malondialdehyde (MDA) concentration within pancreatic gland. These data suggest that activated PMN are an important factor in early AP pathogenesis. Neutrophil aggregation within pancreatic gland modulated by monoclonal antibody CD11b contribute to the extent of injury during the early stage of ceruleine experimental pancreatitis in rats.
Exp Mol Pathol 2004 Aug
PMID:Influence of molecule CD 11b blockade on the course of acute ceruleine pancreatitis in rats. 1521 51

Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation, shock, and pancreatitis in Japan. Recent studies have demonstrated that serine protease inhibitors may play an anti-inflammatory role beyond merely an inhibitory action on neutrophil elastase at the site of inflammation at least in vitro. To clarify the direct contributions of UTI to inflammatory condition in vivo, we analyzed its roles in experimental systemic inflammatory response induced by intraperitoneal administration of lipopolysaccharide (LPS) using UTI deficient (-/-) mice and corresponding wild-type (WT) mice. After LPS (1 mg/kg) challenge, UTI (-/-) mice revealed a significant elevation of plasma fibrinogen and fibrinogen/fibrin degradation products and a decrease in white blood cell counts compared with WT mice. LPS treatment induced more severe neutrophilic inflammation in the lung and the kidney obtained from UTI (-/-) mice than in those from WT mice, which was confirmed by histological examination. The protein levels of proinflammatory mediators, such as macrophage chemoattractant protein (MCP)-1 in the lungs, MCP-1 and keratinocyte chemoattractant (KC) in the kidneys, and interleukin-1beta, macrophage inflammatory protein-2, MCP-1, and KC in the liver, were significantly greater in UTI (-/-) mice than in WT mice after LPS challenge. Our results suggest that UTI protects against systemic inflammatory response and subsequent organ injury induced by bacterial endotoxin, at least partly through the inhibition of the enhanced expression of proinflammatory cytokines and chemokines.
Mol Pharmacol 2005 Mar
PMID:Urinary trypsin inhibitor protects against systemic inflammation induced by lipopolysaccharide. 1557 31

A characteristic feature of all inflammatory disorders is the excessive recruitment of leukocytes to the site of inflammation. The loss of control in trafficking these cells contributes to inflammatory diseases. Leukocyte recruitment is a well-orchestrated process that includes several protein families including the large cytokine subfamily of chemotactic cytokines, the chemokines. Chemokines and their receptors are involved in the pathogenesis of several diseases. Acute lung injury that clinically manifests as acute respiratory distress syndrome (ARDS) is caused by an uncontrolled systemic inflammatory response resulting from clinical events including major surgery, trauma, multiple transfusions, severe burns, pancreatitis, and sepsis. Systemic inflammatory response syndrome involves activation of alveolar macrophages and sequestered neutrophils in the lung. The clinical hallmarks of ARDS are severe hypoxemia, diffuse bilateral pulmonary infiltrates, and normal intracardiac filling pressures. The magnitude and duration of the inflammatory process may ultimately determine the outcome in patients with ARDS. Recent evidence shows that activated leukocytes and chemokines play a key role in the pathogenesis of ARDS. The expanding number of antagonists of chemokine receptors for inflammatory disorders may hold promise for new medicines to combat ARDS.
Am J Physiol Lung Cell Mol Physiol 2005 Jan
PMID:Chemokines in acute respiratory distress syndrome. 1559 Oct 40

Autoimmune pancreatitis, an inflammatory process of the pancreas due to an autoimmune mechanism establishing etiology of chronic pancreatitis, is characterized by the presence of autoantibodies, hypergammaglobulinemia, pancreatic enlargement, pancreatic duct strictures, and pathologic features of fibrotic changes with intense, mainly lymphocytic infiltrations, which may contribute to tissue destruction probably by apoptosis. In almost 60% of the cases, this type of pancreatitis coexists with other autoimmune diseases such as Sjogren's syndrome, sclerosing extrahepatic cholangitis, primary biliary cirrhosis, autoimmune hepatitis, or other extrapancreatic disorders, and recently with gastric peptic ulceration. The diversity of extrapancreatic lesions with similar histopathologic findings suggests general involvement of the digestive system in this disease, although the presence of such involvement has not been fully elucidated. Similarly, Helicobacter pylori (H. pylori) infection, a well known cause of gastric ulcer, has been associated, via molecular mimicry of host structures by its constituents with the same autoimmune conditions, also characterized by fibrotic changes and/or lymphoplasmacytic inflammations, accompanied by aberrations of T cell apoptosis that contribute to hepatobiliary- or extrahepatic-tissue destruction. Considering that H. pylori is involved in the pathogenesis and pathophysiology of these autoimmune disorders, we propose that this organism might trigger autoimmune pancreatitis through induction of autoimmunity and apoptosis.
J Cell Mol Med
PMID:A concept on the role of Helicobacter pylori infection in autoimmune pancreatitis. 1578 77


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