UMLS:C0030305 - FACTA Search

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Query: UMLS:C0030305 (pancreatitis)
16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet-activating factor (PAF) may play a critical and primary role in the pathogenesis of acute pancreatitis and pancreatitis-associated distant organ injury. The present study evaluated the effect of a PAF antagonist, lexipafant (an (S)-4-methyl-2[methyl-imidazo[4,5-c]pyridin-1-ylmethyl)-benzene sulphonyl]-amino]pentanoic acid ethyl ester, BB-882; British Biotech Ltd.), on the potential prevention of gut barrier dysfunction, by measuring gut origin sepsis, bidirectional permeability of the intestinal barrier, and pancreatic capillary endothelial barrier integrity, in acute pancreatitis induced by intraductal infusion of 5% sodium taurodeoxycholate. Pancreatic endothelial permeability significantly increased in animals with acute pancreatitis, whereas pretreatment with lexipafant had a preventive effect (p < 0.05 vs. pancreatitis with saline). Similarly, alterations noted in hematocrit and plasma levels of lipase and calcium were counteracted by the PAF antagonist. It also prevented the increase in albumin leakage from blood to the mucosal interstitium and from blood to the intestinal lumen in acute pancreatitis. Albumin passage from the gut lumen to blood in animals with pancreatitis pretreated with saline increased from 3 h and on, and lexipafant prevented alterations in mucosal epithelial permeability. Bacterial translocation was commonly seen in pancreatitis, whereas only a few positive cultures were observed in pancreatitis animals given lexipafant. Microthrombosis in intestinal villi seemed less frequent after lexipafant pretreatment. We conclude that (a) PAF may play a role in the pathogenesis of pancreatitis-associated intestinal dysfunction, (b) PAF may be involved in the development of distant organ dysfunction by triggering endothelial barrier dysfunction, and (c) PAF antagonists may provide potential agents for preventing pancreatitis-associated gut barrier dysfunction.
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PMID:Effect of a platelet-activating factor antagonist on pancreatitis-associated gut barrier dysfunction in rats. 970 Sep 40

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg(-1)/day(-1)). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN- supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.
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PMID:Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis. 983 29

Bacterial infections, frequently caused by bacteria of enteric origin, are often seen during the progression of severe acute pancreatitis, concomitant with the potential development of multiple organ dysfunction. In the present paper, the complex mechanisms of gut barrier dysfunction and gut origin sepsis in acute pancreatitis are discussed. The individual parts of the gut barrier, e.g. the immunological, bacteriological and morphological (mucus, epithelium, endothelium and interstitium) components, seem to interact and depend on each other. Pancreatitis-induced hypovolaemia due to endothelial barrier leakage and gut arteriovenous shunting causes intestinal ischaemia and reperfusion injury with concomitant gut barrier dysfunction. Gut endothelial barrier dysfunction probably plays a central role. Potential molecular mechanisms could, among others, be associated with alterations in intracellular signal transduction, intercellular signalling and expression of adhesion molecules on endothelial cells. The mechanisms underlying gut barrier dysfunction in acute pancreatitis are thus complex and still not fully elucidated. Knowledge about the regulating events will probably allow future pharmacological therapy for prevention and treatment of the severe complications of acute pancreatitis, including gut barrier dysfunction.
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PMID:Gut barrier dysfunction in experimental acute pancreatitis. 1037 40

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 c 0.06 vs. 1.98 +/-0.04 nl x min(-1) x cap(-1) [control]; P = NS), whereas mucosal (1.59 +/-0.03 vs. 2.28 +/-0.03 nl x min(-1) x cap((-1))[control]; P <0.01) and subserosal (2.47 +/-0.04 vs. 3.74 +/-0.05 nl x min(-1) x cap((-1))[control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 +/-0.03 vs. 1.98 +/-0.04 nl x min(-1) x cap(-1) [control]; P <0. 01) and colonic (mucosal: 0.59 +/-0.01 vs. 2.28 +/-0.03 nl x min(-1) x cap((-1))[control], P <0.01; subserosal: 1.96 +/-0.05 vs. 3.74 +/-0.05 nl x min(-1) x cap(-1) [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 +/-19 nmol x thr(-1) x cm(-2); mild pancreatitis: 158 +/-23 nmol x hr(-1) x cm(-2); severe pancreatitis: 181 +/-33 nmol x hr(-1) x cm(-2); P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation.
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PMID:Intestinal microcirculation and gut permeability in acute pancreatitis: early changes and therapeutic implications. 1045 30

Failure of intestinal barrier function and subsequent translocation of bacteria from the gut are believed to play a decisive role in the development of systemic septic complications, for example, following major trauma or major abdominal surgery. This study evaluated: (a) the effect of glutamine on colonic microcirculation and electrophysiological parameters reflecting gut barrier function, (b) the translocation of live bacteria to extraintestinal organs, and (c) disease outcome in two animal models with impaired gut barrier function. Severe acute pancreatitis or colitis was induced in rats randomized for therapy with or without glutamine (0.5 g/kg daily). After 48 h one animal group was prepared for intravital microscopy of colonic capillary blood flow and electrophysiological measurement of gut permeability; another was killed after 96 h for histological and microbiological examination. In animals with pancreatitis, glutamine (Gln) supplementation significantly improved gut permeability, i.e., Gln increased colonic transmucosal resistance from 67+/-7 to 92+/-3 Omega/cm(2) and decreased mannitol flux through the epithelium by 53%. Capillary blood flow in the colonic mucosa was improved by 25%. The prevalence of pancreatic infections was reduced from 86% in animals on standard parenteral nutrition to 33% in animals given the Gln-enriched diet (P<0.05); mortality decreased by 32%. In colitis, Gln had no significant effect on these parameters except for improving colonic capillary blood flow in colon segments not adjacent to the major injury site. Glutamine supplementation improves colonic capillary blood flow, stabilizes gut permeability, and reduces secondary pancreatic infections and mortality in severe rodent pancreatitis, but it is not helpful in colitis. This confirms previous reports that glutamine stabilizes gut barrier function only in certain diseases. Our experimental data strongly suggest that acute pancreatitis (rather than colitis) is one of the diseases with gut barrier dysfunction in which glutamine substitution may be helpful to reduce bacterial translocation and should therefore be tested in a controlled clinical trial.
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PMID:Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier. 1046 Sep 4

It has been postulated that in severely ill patients splanchnic hypoperfusion may cause endotoxin release from the gut, and this leakage of endotoxin into the circulation can trigger the cascade of inflammatory cytokines. We tested this hypothesis in 9 patients with acute severe pancreatitis by monitoring gastric intramucosal pH (pHi) as measure of splanchnic hypoperfusion at 12-h intervals trying to correlate it to endotoxin and cytokine release. Only 3 of 59 samples, obtained from 3 patients contained circulating endotoxin. Thirteen of 15 plasma samples drawn at pHi <7.20 did not contain endotoxin. The pHi was significantly lower in patients who subsequently developed 3 or more organ failures (P = 0.0017, analysis of variance). Although endotoxemia was only occasionally found, most patients had measurable interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) in their plasma. Concentrations of IL-6, IL-8, and IL-10 on admission correlated to degree of organ dysfunction as measured by the multiple organ system failure score (P = 0.035, r = 0.74; P = 0.010, r = 0.91; P = 0.021, r = 0.82, respectively). In conclusion, patients with acute, severe pancreatitis often have splanchnic hypoperfusion and produce a wide array of cytokines despite a rare occurrence of endotoxemia.
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PMID:Intramucosal pH and endotoxin and cytokine release in severe acute pancreatitis. 1063 74

Acute pancreatitis is a disease process that begins with an initial injury to the pancreatic acinar cell due to the erroneous premature activation and intracellular release of digestive enzymes. The local injury is amplified through the induction of a systemic inflammatory response, mediated by the generation and release of cytokines and an aggressive inflammatory cell recruitment. Failure to maintain gut integrity may exacerbate the stress response and the systemic inflammatory reaction associated with this process, worsening the overall clinical severity of the pancreatitis and contributing further to complications of organ failure and nosocomial infection. Emphasis in the clinical nutritional management of these patients has shifted from efforts to minimize stimulation of the gland, to attaining enteral access, starting tube feeds low in the gastrointestinal tract, and monitoring tolerance. While clinical guidelines help identify those patients with acute pancreatitis at greatest need for aggressive nutritional support, the proper timing to initiate feeding, the optimal composition of the enteral formula, and whether or not enteral feeding is better than no nutritional therapy is still not clear from the current literature.
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PMID:Artificial nutrition in pancreatic disease: what lessons have we learned from the literature? 1070 May 27

Infection is the most common cause of death in acute pancreatitis. Earlier studies have demonstrated that early enteral nutrition decreases microbial translocation, upregulates the immune function and reduces septic complications and mortality. Lactobacillus plantarum (Lp) has been shown to be effective in reducing egress of endotoxin and microbial strain that showed very high adherence power to gut mucosa. We adopted a model of acute pancreatitis induced by isolation and ligation of biliopancreatic duct in adult Lewis rats. Three groups were studied: A. control group (sham operation); B. induced pancreatitis, no further treatment; C. Induced pancreatitis + gavage with 5 ml/day of a suspension of Lp 299 v in a dose of 0.5-1.0 x 10(9)/ml during 4 days before and 4 days after induction of pancreatitis. All animals were sacrificed after 96 hours. Histological studies and microbiological analyses were performed. Forty out of 55 animals showed signs of severe pancreatitis on sacrifice after 96 hours. Only these animals were further studied. In group A, we found only 1/20 bacteria in mesenteric nodes (MN). Pathogenic microrganisms were found in the non-treated group in MN in 14/20 and in the pancreatic tissue in 10/20. In contrast, when kept on an umbrella of Lp 299 v, only 4/20 animals demonstrated growth of enteric bacteria in MN and 3/20 in pancreatic tissue. All of these results showed a significant reduction of infection in the treated groups. In our model, Lp 299 v is effective in preventing microbial translocation in experimental pancreatitis. Treatment with probiotic bacteria, such as Lactobacillus spp, seems to be a promising alternative as problems with antibiotic-resistant bacteria seem to accumulate.
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PMID:[A probiotic as an antagonist of bacterial translocation in experimental pancreatitis]. 1079 68

Interleukin (IL)-11 has anti-inflammatory activity in animal models of gut inflammation, endotoxemia, and radiation-induced thoracic injury. The aim of the present study was to investigate the protective role of IL-11 in a model of acute necrotizing pancreatitis in mice. Acute pancreatitis was induced by administration of seven intraperitoneal injections of cerulein (50 microg/kg) at hourly intervals. Lipopolysaccharide (LPS) was injected 5 hours after the first cerulein injection. Treatment with recombinant human IL-11 (rhIL-11) was started 30 minutes before the first cerulein injection and repeated 4 hours later. Serum levels of amylase, lipase, and tumor necrosis factor (TNF)-alpha were measured at the end of the experiments. The severity of pancreatitis was evaluated by histological scoring using a semiquantitative analysis of hematoxylin and eosin-stained sections of the pancreas. Competitive reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the intrapancreatic TNF-alpha mRNA levels. Serum amylase and lipase levels progressively increased with a maximum reached between 8 and 11 hours. Treatment with rhIL-11 significantly decreased amylase and lipase levels at 6 and 8 hours. Serum TNF-alpha peaked at 6 hours and rapidly decreased thereafter. The elevation of serum TNF-alpha was markedly inhibited by treatment with rhIL-11. Histologically, treatment of rhIL-11 reduced the severity of pancreatic injury including edema, inflammatory cell infiltration, and hemorrhage at 6 hours. Intrapancreatic TNF-alpha mRNA levels were reduced by >50% in the rhIL-11-treated group at 6 hours. In conclusion, rhIL-11 decreased the severity of experimental pancreatitis early on but not later and inhibited the intrapancreatic TNF mRNA expression in vivo, suggesting that the protective effect of IL-11 during the early stage of acute pancreatitis may be mediated, at least in part, through modulation of TNF production.
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PMID:Recombinant human interleukin-11 decreases severity of acute necrotizing pancreatitis in mice. 1097 6

Conventional wisdom has previously dictated that, in order to avoid stimulation of pancreatic secretion during acute pancreatitis, and thus avoid the perpetuation of the enzymatic activation from which the pancreatitis originated, enteral feeding should be avoided. With greater understanding of the potential role of the gastrointestinal tract in the development of a systemic inflammatory response within a number of scenarios, this dogma has recently been challenged. Moreover, there is some evidence to suggest that starving the gastrointestinal tract and providing nutritional support via the parenteral route may be associated with an increased incidence of septic complications. Experimental and clinical evidence suggests that feeding the gut may diminish intestinal permeability to endotoxin and diminish bacterial translocation, thus reducing the cytokine drive to the generalized inflammatory response and preventing organ dysfunction. Preliminary experience suggests that the institution of jejunal (but not gastric or duodenal) nutrition within 48 hours of the onset of severe acute pancreatitis diminishes endotoxic exposure, diminishes the cytokine and systemic inflammatory responses, avoids antioxidant consumption and does not cause the radiological appearances of the pancreas to deteriorate. These observations are paralleled by improvements in clinical outcome measures such as intensive care unit stay, septic complications and mortality. Whist parenteral nutrition continues to have a role in the management of acute pancreatitis particularly when complicated by fistulae or prolonged ileus, the early introduction of jejunal nutrition merits further investigation in acute pancreatitis.
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PMID:Enteral versus parenteral nutrition in acute pancreatitis. 1103 Jun 11

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