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)

NADPH oxidase produces a large amount of reactive oxygen species (ROS) mainly in phagocytic cells. ROS are involved in NF-kappaB activation, cytokine expression and thus, pathogenesis of pancreatitis. However, the source of ROS in pancreatic acinar cells has not been clarified. Cerulein rapidly induces acute and edematous form of pancreatitis. We investigated whether pancreatic acinar cells contain NADPH oxidase, and whether NADPH oxidase mediates interleukin-6 (IL-6) in pancreatic acinar AR42J cells stimulated with cerulein. Expression of NADPH oxidase subunits and NADPH oxidase activity were determined in the cells by immunofluorescence staining and lucigenin luminescence, respectively. Oxidant-sensitive nuclear transcription factor NF-kappaB activation was monitored by electrophoretic mobility shift assay. IL-6 expression was determined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbant assay. NADPH oxidase inhibitor diphenylene iodonium (DPI), antioxidant rebamipide, and antisense oligonucleotides (AS ODNs) for NADPH oxidase subunits p22phox and p47phox were used to determine the involvement of NADPH oxidase in NF-kappaB activation and IL-6 expression in AR42J cells. As a result, pancreatic acinar AR42J cells constitutively express NADPH oxidase subunits p67phox and p47phox in the cytosol and Nox1 and p22phox in the membrane. Cerulein-stimulated NADPH oxidase activity and induced NF-kappaB activation and IL-6 expression in AR42J cells. Treatment of DPI or rebamipide and transfection of AS ODNs for NADPH oxidase subunits suppressed cerulein-induced NF-kappaB activation and IL-6 expression compared to S ODNs. In conclusion, NADPH oxidase may mediate the expression of inflammatory cytokines by stimulating NF-kappaB activation in pancreatic acinar cells during the course of pancreatitis.
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PMID:NADPH oxidase mediates interleukin-6 expression in cerulein-stimulated pancreatic acinar cells. 1583 77

The aim of this study was to investigate the influence of N-acetylcysteine (NAC) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increase in mortality rate, pancreatic necrosis and serum activity of amylase, alanine aspartate transferase (ALT), interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and significant decrease of concentrations of calcium, blood pressure, urine output and pO(2). The use of NAC inhibited the changes in urine output, pO(2), tissue activity of MPO and MDA in pancreas and lungs, and the serum activity of IL-6, ALT, and serum concentrations of urea and calcium. NAC reduced the mortality and pancreatic damage. The use of NAC has a beneficial effect on the course of ANP in rats. It may be used in the treatment of acute pancreatitis.
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PMID:Effects of N-acetylcysteine on acute necrotizing pancreatitis in rats. 1608 83

It has recently been recognized that anandamide (arachidonylethanolamide), which is an endogeneous-cannabinoid (endocannabinoid), mediates septic shock. Cannabinoid means a mind-active material in cannabis (marijuana). Anandamide is mainly produced by macrophages. Cannabinoid 1 (CB1) receptor, which is one of the cannabiniod receptors, is also known to mediate hypotensive shock. The role of endocannabinoids in the progression of acute pancreatitis is unclear. The aims of this study are to clarify their relationship and to find a new therapeutic strategy by regulating the endocannabinoid signaling in acute pancreatitis. Male Wistar rats were injected with caerulein intravenously to induce mild edematous pancreatitis or injected with 5% sodium taurocholate to the bilio-pancreatic duct to induce severe necrotizing pancreatitis. The animals in the latter group were also injected with a CB1 receptor antagonist, AM251, or vehicle solution to see if the inhibition of endocannabinoids improves their survival. Plasma anandamide level was measured by the liquid chromatography/tandem mass spectrometry method. In both models of acute pancreatitis, the plasma anandamide levels were increased, and the levels were significantly higher in rats with severe necrotizing pancreatitis than those in rats with mild edematous pancreatitis. The mean arterial pressure and survival rate were significantly improved by the treatment with AM251, despite that the local inflammatory changes in the pancreas and various parameters (white blood cells, hematocrit, serum amylase, and serum interleukin-6) were similar. This is the first report to show that endocannabinoids are involved in the deterioration of acute pancreatitis and that the down-regulation of endocannabinoid signaling may be a new therapeutic strategy for severe acute pancreatitis.
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PMID:The cannabinoid 1 receptor antagonist, AM251, prolongs the survival of rats with severe acute pancreatitis. 1614 78

Enteral nutrition, as demonstrated by the many published papers, is not only safer and cheaper than parenteral supply of nutrients, but modulates an exaggerated cytokine response related to surgical trauma that leads to an increase in intestinal permeability, bacterial translocation and infection. The aim of enteral nutrition is to reduce the impact of cytokines on surgical patients and the related infectious complications. Via the enteral route the nutrients can reach the bowel lumen where enterocytes draw upon their fuel, preserving the barrier effect and modulating the cytokine response. Parenteral supply does not achieve this target since the blood supply of nutrients is not as important as the luminal supply. It is only via the enteral supply route that we can preserve the barrier effect. Since the cytokine response sets in immediately after a trauma such as surgery, we implement uninterrupted enteral nutrition, which means before, during and after surgery, plus parenteral support till the full calorie intake is achieved. In a hepatic resection study, we have demonstrated that enteral nutrition modulates the interleukin-6 immunological response and shortens both the period to bowel movement resumption and the duration of hospital stay. Aggressive enteral nutrition has also been implemented in severe pancreatitis, allowing control of the disease without the onset of septic complications. The most important target is not to achieve full calorie intake rapidly, but to supply the enteric mucosa continuously with useful immuno-nutrients, such as glutamine and fibres, to preserve the barrier effect, the mucus layer, and immunological status of the mucosa. In this way we have obtained significant results in the surgical treatment of these patients, reducing the infection rate and hospital stay. New prospects may be,possible in the fight against surgical infections by adding probiotics to enteral nutrition in order to improve the microenvironment of the colon.
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PMID:[Perioperative enteral nutrition]. 1623 16

Gabexate mesilate is a synthetic protease inhibitor. The effectiveness of gabexate mesilate in patients with acute pancreatitis is controversial. Proinflammatory cytokines are associated with systemic inflammatory response syndrome (SIRS) in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with SIRS. We investigated the effects of gabexate mesilate on acute necrotizing pancreatitis in rats, emphasizing the changes in serum levels of proinflammatory and anti-inflammatory cytokines. Acute necrotizing pancreatitis was induced by retrograde infusion of sodium taurodeoxycholate into the pancreatobiliary duct in rats. The rats were divided into three groups. Group I was given gabexate mesilate 2 mg/kg/h i.v. continuously 1 h before the induction of acute pancreatitis. Group II was given gabexate mesilate the same dose immediately after the induction of acute pancreatitis. Group III was given normal saline as the controls. Serum levels of amylase, lipase, tumor necrosis factor alpha, interleukin-6, and interleukin-10, pancreatic histopathology and hemodynamics were examined at 5h after the induction of acute pancreatitis. Gabexate mesilate significantly reduced serum levels of amylase, lipase, tumor necrosis factor alpha and interleukin-6 at 5 h. Serum levels of interleukin-10 significantly increased in Group I, as compared with Groups II and III. The severity of pancreatic histopathology, the reduction of mean arterial pressure, the volume of ascites and pancreatic wet weight/body weight ratios were also significantly improved by the administration of gabexate mesilate. The beneficial effects of gabexate mesilate on acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses.
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PMID:Effects of gabexate mesilate on serum inflammatory cytokines in rats with acute necrotizing pancreatitis. 1647 21

The aim of this study was to investigate the influence of U-74389G on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in a significant increase in mortality rate, pancreatic necrosis, and serum levels of amylase, alanine aminotransferase, interleukin-6, tumor necrosis factor alpha, and urea, in lactate dehydrogenase levels in bronchoalveolar lavage fluid, and in the activities of myeloperoxidase and malondialdehyde in pancreas and lung tissue; a significant decrease was observed in serum calcium levels, blood pressure, urine output, and pO(2). The use of U-74389G inhibited the changes in serum urea, pO(2), and tissue levels of myeloperoxidase and malondialdehyde in pancreas and lungs. Moreover, it indicated a limited effect on the course of ANP in the rats and did not reduce mortality and pancreatic damage. Therefore, it may be used in the treatment of lung injury during acute pancreatitis.
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PMID:Effects of lazaroid U-74389G on acute necrotizing pancreatitis in rats. 1655 23

The incidence of severe acute pancreatitis is about 30 cases per 100,000 inhabitants, and it carries an overall mortality rate of 10-15%. Infection of pancreatic necrosis occurs in 20-30% of patients with severe acute pancreatitis and triples the mortality rate. Therefore, early prediction and diagnosis of infection in necrotizing pancreatitis are extremely important. The aim of the studies included in this review was to investigate the potential of specific prognostic factors to predict the development of secondary pancreatic infection in severe acute pancreatitis. This is seen as an important tool allowing to perform a computed tomography- or ultrasound-guided fine needle aspiration for bacteriological sampling at the right moment, to confirm the diagnosis, and, finally, to select the subgroup of patients who would benefit from the antibiotic prophylaxis. Precise patients' selection could possibly result in more rational use of antibiotics in patients with acute necrotizing pancreatitis and reduction of multi-resistant bacteria. Recent studies show that C-reactive protein is an important prognostic marker of pancreatic necrosis with the highest sensitivity and negative prognostic value in this respect. Procalcitonin alone or in combination with interleukin-6 best identifies patients not at risk for infection. However, a review of the clinical studies suggests that we still do not have an optimal model, thus there is a need for new more reliable biochemical and/or clinical predictive systems.
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PMID:Predicting development of infected necrosis in acute necrotizing pancreatitis. 1681 37

Retrospective analysis of 99 consecutive cases of acute severe pancreatitis established presence of systemic inflammation in all patients. Magnitude of acute phase response was characterised by C-reactive protein and Interleukin-6 values. Progression to multiple organ failure raised considerably lethality. Failure developed more frequently in respiratory system, liver and kidneys. General mortality was 38,4%.
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PMID:[Sepsis in acute severe pancreatitis]. 1692 13

Peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors that regulate cellular energy and lipid metabolism. PPAR-gamma agonists also have potent anti-inflammatory properties through down-regulation of early inflammatory response genes. The role of PPAR-gamma in acute pancreatitis has not been adequately examined. In this study, we determined the effect of PPAR-gamma agonists on the severity of pancreatitis and sought to correlate PPAR-gamma expression in pancreatic acinar cells and the severity of acute pancreatitis in vivo. Acute pancreatitis was induced in mice by hyperstimulation with the cholecystokinin analog, cerulein. PPAR-gamma agonists were administered by intraperitoneal injection 15-30 minutes before induction of pancreatitis (pretreatment) or at various times after induction of pancreatitis (treatment). Pancreata and serum were harvested over the course of 24 hours. Serum amylase activity and glucose levels were measured. Pancreata were used for histological evaluation as well as protein and mRNA analysis. Pretreatment of mice with the PPAR-gamma agonists 15-deoxy-Delta12, 14-prostaglandin J(2), or troglitazone significantly reduced the severity of pancreatitis in a dose-dependent manner. This reduction was indicated by reduced serum amylase activity and histological damage (leukocyte infiltration, vacuolization, and necrosis). Although cerulein decreased PPAR-gamma expression in the pancreas, pretreatment with agonists maintained PPAR-gamma expression early in acute pancreatitis. The expression of PPAR-gamma inversely correlated with pancreatitis severity and expression of the proinflammatory cytokines, interleukin-6, and tumor necrosis factor-alpha. Treatment with troglitazone after the induction of pancreatitis reduced serum amylase activity. The results suggest that PPAR-gamma plays a direct role in the inflammatory cascade during the early events of acute pancreatitis. Our data are the first to demonstrate that PPAR-gamma agonists represent a promising therapeutic strategy for acute pancreatitis.
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PMID:Anti-inflammatory effects of PPAR-gamma agonists directly correlate with PPAR-gamma expression during acute pancreatitis. 1696 31

Acute pancreatitis is a process that continues to interest physicians and research scientists. Understanding potential factors initiating acute pancreatitis, mechanisms regulating the local and distant inflammatory response, methods for accurately predicting outcome, and possible therapeutic interventions continue to be investigated. Current interest in inflammatory response of the acute injury focuses on proinflammatory and anti-inflammatory cytokines as markers for disease severity and predictors of outcome. Recent studies confirm the utility of physical examination and existing markers such as C-reactive protein and interleukin-6 in predicting the severity of acute pancreatitis. Understanding the molecular mechanism of lung injury remains a major focus for future therapeutic targets, since pancreatitis-associated pulmonary injury results in significant morbidity and is a major indication for intensive care unit admissions.
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PMID:Acute pancreatitis. 1703 Nov 11


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