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)

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and development 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-kappaB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H(2)O(2) 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). Neutrophils generated ROS by stimulation with PMA, which was inhibited by NAC and SOD. In acinar cells, PMA-primed neutrophils increased the productions of H(2)O(2), LPO, and cytokines both time and dose dependently. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer) in acinar cells. Both NAC and SOD inhibited neutrophil-induced, oxidant-mediated 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 useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-kappaB and decreasing cytokine production.
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PMID:Suppression of NF-kappaB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells. 1103 20

To assess the level of oxidative stress, measured as prooxidant-antioxidant imbalance in the blood of patients with alcohol-related injury of the liver and pancreas, we determined superoxide ion (O2*-) production by neutrophils isolated from the peripheral blood of 3 groups of patients. Patients with compensated alcoholic liver cirrhosis (n=16), with alcoholic chronic pancreatitis (n=20), and with concomitant cirrhosis and pancreatitis (n=10) were included in this study. All patients had consumed at least 70 g of pure alcohol per day over 5 years. They had not abstained before admission to hospital. The control group consisted of 16 healthy non-alcohol-abusive subjects. As antioxidative enzymes (AOE) present in sera play a very important role in the regulation of plasma reactive oxygen species (ROS) levels and in the protection of plasma compounds against ROS action, we also examined the serum activity of catalase (CAT), superoxide dismutase (SOD), total activity, and the glutathione peroxidase (GPx) serum concentration. Neutrophils of patients with concomitant alcoholic liver cirrhosis and pancreatitis exhibited, similarly to the neutrophils of patients with chronic alcoholic pancreatitis, an enhanced ability to produce superoxide anions in vitro. In contrast, neutrophils of patients with alcoholic liver cirrhosis exhibited a defect in resting and PMA-induced superoxide anion production. The AOE activity in the sera of patients was also significantly changed. Total SOD activity was enhanced in all groups of patients with alcoholic liver cirrhosis, chronic pancreatitis and with concomitant injury of both organs. CAT activity was only increased in the sera of patients with liver cirrhosis or pancreatitis, but not in the patients with concomitant cirrhosis and pancreatitis. GPx concentration was only diminished in the patients with chronic pancreatitis. It seems likely that oxidative stress, defined as the imbalance between prooxidant and antioxidant activity, is highest in the blood of patients with chronic pancreatitis and, especially, in patients with concomitant liver cirrhosis and pancreatitis.
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PMID:Alcohol-related cirrhosis with pancreatitis. The role of oxidative stress in the progression of the disease. 1134 18

Reactive oxygen species are considered important regulators in the pathogenesis and in the development of pancreatitis. The transcription factor nuclear factor kappaB (NF-kappaB) is activated by reactive oxygen species and regulates the gene expressions of inflammatory cytokines. The present study investigates (1) the susceptibility of isolated rat pancreatic acinar cells to oxidant attacks produced by adenosine diphosphate/ferrous iron, hypoxanthine/xanthine oxidase, and neutrophils primed with 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) and (2) the potential of small-molecule antioxidants (N-acetylcysteine, beta-carotene, rebamipide, allopurinol) and superoxide dismutase (SOD) to prevent such injury and oxidant-mediated NF-kappaB activation and inflammatory cytokine production in the cells. As a result, oxidative stress resulted in a time-dependent increase in lipid peroxide production in pancreatic acinar cells which was inhibited by small-molecule antioxidants and SOD. PMA-primed neutrophils induced NF-kappaB activation and increased the production of cytokines (IL-6, TNF-alpha) in the cells. This was in parallel with lipid peroxide production. Small-molecule antioxidants and SOD inhibited NF-kappaB activation and cytokine production in acinar cells caused by PMA-primed neutrophils. In conclusion, oxidative stress activates NF-kappaB, resulting in upregulation of inflammatory cytokines in pancreatic acinar cells. Small-molecule antioxidants might be clinically useful anti-inflammatory agents by inhibiting oxidant-induced cytokine production.
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PMID:Oxidative stress induced cytokine production in isolated rat pancreatic acinar cells: effects of small-molecule antioxidants. 1180 45

AIM:To observe the changes in oxygen free radical (OFR) and the curative effect of traditional Chinese medicine Qing Yi Tang in acute necrotizing pancreatitis (ANP).METHODS:After induction of ANP by injection of sodium taurocholate into pancreatic duct, 16 dogs were randomly divided into control group and Chinese medicine group.Serum amylase, SOD and MDA were determined on postoperative day 1, 2, 4 and 7. The animals were sacrificed on day 7. SOD and MDA in organs were determined, and pathological changes in pancreas were observed.RESULTS: As compared with control group, the serum level of amylase (734U/L vs 2783U/L) and MDA (7.8nmol/ml vs 14.8nmol/ml) in Chinese medicine group were decreased on day 7 (P < 0.05), while SOD increased significantly (281nU/ml vs 55nU/ml, P < 0.01), and similar changes occurred in MDA and SOD in organs, especially in the pancreas; the pathological changes in the pancreas were alleviated as well.CONCLUSION: Qing Yi Tang is effective in clearing OFRs and alleviating pathological changes in ANP.
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PMID:Traditional Chinese medicine Qing Yi Tang alleviates oxygen free radical injury in acute necrotizing pancreatits. 1181 20

Reactive oxygen species (ROS) has been considered to be an important regulator in the development and pathogenesis of pancreatitis and an activator of the transcription factor, nuclear factor-kappaB (NF-kappaB), regulating inflammatory cytokine gene expression. NF-kappaB activation was demonstrated in cerulein pancreatitis, which rapidly induces an acute, edematous form of pancreatitis. This study aimed to investigate whether cerulein induced ROS generation, lipid peroxide and hydrogen peroxide production, NF-kappaB activation, and expression of cytokines (IL-1beta, IL-6) in pancreatic acinar cells. An additional aim was to establish whether these alterations were inhibited by antioxidants such as glutathione, superoxide dismutase, and catalase and an inhibitor of NF-kappaB activation, pyrrolidine dithiocarbamate (PDTC). To determine the possible interactions of the antioxidants and PDTC with cerulein-induced signaling, Ca2+ signal and amylase release were monitored in the pancreatic acinar cells treated with cerulein in the presence or absence of either the antioxidants or PDTC. The results showed that cerulein generated ROS and increased lipid peroxide and hydrogen peroxide production in the acinar cells, as determined by dichlorofluorescein diacetate dye. This resulted in NF-kappaB activation and the induction of cytokine gene expression in the cells. The cerulein-induced NF-kappaB activation was in parallel to IkappaBalpha degradation. Cerulein also induced Ca2+ signals and amylase release in acinar cells. Both antioxidants (glutathione, superoxide dismutase, catalase) and PDTC inhibited the cerulein-induced, oxidant-mediated alterations but did not affect the cerulein-evoked Ca2+ signals and amylase release in acinar cells. In conclusion, ROS, generated by cerulein, activates NF-kappaB, resulting in the up-regulation of inflammatory cytokine gene expression in acinar cells. NF-kappaB inhibition by scavenging ROS might alleviate the inflammatory response in pancreatic acinar cells by suppressing cytokine gene expression.
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PMID:Suppression of cerulein-induced cytokine expression by antioxidants in pancreatic acinar cells. 1237 70

The assumption that the endoscopist is an important factor in outcome of ERCP is not easy to document. There are plenty of reasons for the difficulties in defining experience and skill of an endoscopist, and establishing suitable endpoints for their measurement. Suitable proxy variables are ERCP-frequency (ongoing volumes) and ERCP-experience (life-time volumes) of the endoscopist, as well as individual and institutional conditions. Important confounders are difficulty of ERCP, patient-related and procedure-related risk factors and risk-reducing factors. Endpoints should include success and (specific) complications of ERCP. Only few studies are available that analyse the influence of the endoscopist's skills on post-ERCP pancreatitis. Studies with a high preponderance of dominating patient-related risk factors for post-ERCP pancreatitis, e.g. suspect of SOD and unexplained abdominal pain, failed to prove such a dependence. On the other hand, evidence increases from studies with patient populations of more traditional indications for ERCP that suggests the existence of an association between ERCP-frequency of the endoscopist or ERCP-frequency of the environment and the incidence of post-ERCP pancreatitis and other complications. ERCP-experience measured in overall live-time volumes, however, does not seem to influence the risk of pancreatitis due to ERCP, although the data are very limited. During the ERCP-training of young endoscopists an impaired success rate appears more important than an increased complication rate. Nevertheless, all undesired outcomes of ERCP should be applied to the endpoints of quality assessment in ERCP-training. Further studies on this topic are needed. Since many variables significantly interact with the endpoints post-ERCP pancreatitis and complications of ERCP, a special study design appears indispensable to conclusively prove a relationship between an endoscopist's expertise and specific complications of ERCP.
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PMID:Post-ERCP pancreatitis: is the endoscopist's experience the major risk factor? 1243 84

The aim of this study was to evaluate the RBC deformability and oxidative stress parameters during acute pancreatitis. Healthy volunteers and patients with mild or severe acute pancreatitis were evaluated. There were no changes in erythrocyte's deformability in patients with mild acute pancreatitis. In severe acute pancreatitis loss of deformability of erythrocytes was observed. Serum lipofuscin level increased both in mild and severe form of the disease. The superoxide dismutase (SOD) activity was increased in erythrocytes from mild and severe form without systemic complications and was positively correlated with erythrocyte's deformability in a severe form of acute pancreatitis. Significant positive correlation between serum total antioxidant status and deformability of erythrocytes in healthy humans and negative correlation in mild pancreatitis were found.
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PMID:Red blood cells deformability and oxidative stress in acute pancreatitis. 1245 71

In dogs with acute reflux pancreatitis specific activity of superoxide dismutase in the pancreas rapidly increased (over 15 min). Activation of this enzyme by free oxygen radicals was demonstrated in in vitro experiments. Treatment with allopurinol prevented activation of superoxide dismutase. Our results indicate that superoxide ions are generated in the pancreas at the early stage of acute reflux pancreatitis due to activation of xanthine oxidase.
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PMID:Generation of free oxygen radicals in the pathogenesis of experimental acute reflux pancreatitis. 1245 61

Various protocols may be used for acute pancreatitis treatment. Recently, the benefit of hyperbaric oxygen (HBO) has been demonstrated. To clarify the mechanism of HBO on the process of the acute pancreatitis, we determined the levels of antioxidant enzymes in an acute pancreatitis model. Forty-five Sprague-Dawley rats were randomly divided into three groups: Group I: sham group (n=15), Group II: pancreatitis group (n=15), Group III: pancreatitis group undergoing HBO therapy (n=15). HBO was applied postoperatively for 5 days, two sessions per day at 2.5 fold absolute atmospheric pressure (ATA) for 90 min. Superoxide dismutase (Cu/Zn-SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH Px) activity were measured in pancreatic tissue and erythrocyte lysate. MDA and GSH Px were also determined in plasma. In addition, amylase levels were measured in the serum. While serum amylase levels and MDA values in erythrocyte, plasma and pancreatic tissue were decreased, the levels of GSH Px and SOD were found to be significantly increased in the Group III as compared to those of the Group II. The findings of our study suggest that HBO has beneficial effects on the course of acute pancreatitis and this effect may occur through the antioxidant systems.
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PMID:The effect of hyperbaric oxygen treatment on oxidative stress in experimental acute necrotizing pancreatitis. 1262 15

Functional biliary disorders encompass the conditions of SOD and gallbladder dysmotility, both of which result in clinical pain syndromes. Obtaining objective diagnostic and outcomes data for both disorders has been an ongoing challenge over the last two decades. SOD, although initially believed to be strictly a biliary disorder, has now been implicated in recurrent pancreatitis. The biliary-type classification allows a clinician to stratify patients who would benefit from SOM and endoscopic sphincterotomy. Further study into the impact of endoscopic therapy for recurrent pancreatitis is needed. By the same token, the dilemma of postcholecystectomy abdominal pain, whether classified as biliary or pancreatic type III, remains challenging. The current limitations of knowledge highlight the need for prospective randomized studies to evaluate the clinical significance of SOM abnormalities to facilitate treatment of these patients.
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PMID:Sphincter of Oddi dysfunction and other functional biliary disorders: evaluation and treatment. 1285 8


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