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)

Infective complications play major role in mortality of high risk patients demanding intensive care. Selective Bowel Decontamination prevents endogenous infections by reducing the number of potentially pathogen microbes (aerobic bacteria, fungi) in the oropharynx and gastrointestinal tract, saving anaerobic bacteria. It had been used 20 years ago for the first time. Authors survey it's literature ever since. Selective Bowel Decontamination is performed by the mixture of antibiotics and antimycotic drug, administered orally in hydrogel, and suspension form in nasojejunal tube. The number of Gram negative optional aerobic bacteria and fungi decrease significantly in the gut, and the microbial translocation is following this tendency. Foreign authors achieved good results in acute necrotizing pancreatitis, after liver transplant, in polytrauma, in serious burn and in haematological malignancies. According to the literature Selective Bowel Decontamination shows advantages in selected groups of high risk surgical patients. In some studies the administration took few months, but the minimum time was one week. There was no report of increasing MRSA appearance. Regular bacteriological sampling is highly recommended in order to recognize any new antibiotic resistance in time.
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PMID:[Selective bowel decontamination]. 1671 71

Fat necrosis in pancreatitis has been reported in mesentery, gut serosa and distant sites like subcutaneous fat and fatty marrow. We present a case of chronic pancreatitis wherein fat necrosis was seen in the muscularis propria and submucosa of small intestine in addition to the serosa. Saponified fatty acid crystalloids, not seen in every case, were seen in these foci of fat necrosis.
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PMID:Migration of steatonecrosis in pancreatitis. 1718 48

The pancreatic acinus is the functional unit of the exocrine pancreas whose role is to secrete zymogens into the gut lumen for food digestion via apical exocytosis. We previously reported that supramaximal CCK induced apical blockade and redirected exocytosis to ectopic sites on the basolateral plasma membrane (BPM) of this polarized cell, leading to pancreatitis. Basolateral exocytosis was mediated by protein kinase C phosphorylation of BPM Munc18c, causing its displacement into the cytosol and activation of BPM-bound Syntaxin-4 to form a SNARE complex. To mimic the conditions of alcoholic pancreatitis, we now examined whether 20 mm alcohol followed by submaximal CCK might mimic supramaximal CCK in inducing these pathologic exocytotic events. We show that a non-secretory but clinically relevant alcohol concentration (20 mm) inhibited submaximal CCK (50 pM)-stimulated amylase secretion by blocking apical exocytosis and redirecting exocytosis to less efficient BPM, indeed mimicking supramaximal CCK (10 nM) stimulation. We further demonstrate that basolateral exocytosis caused by both stimulation protocols is mediated by PKC alpha-induced phosphorylation of Munc18c: 1) PKC alpha is activated, which binds and induces phosphorylation of PM-Munc18c at a Thr site, and these events can be inhibited by PKC alpha blockade; 2) PKC alpha inhibition blocks Munc18c displacement from the BPM; 3) PKC alpha inhibition prevents basolateral exocytosis but does not rescue apical exocytosis. We conclude that 20 mm alcohol/submaximal CCK as well supramaximal CCK stimulation can trigger pathologic basolateral exocytosis in pancreatic acinar cells via PKC alpha-mediated activation of Munc18c, which enables Syntaxin-4 to become receptive in forming a SNARE complex in the BPM; and we further postulate this to be an underlying mechanism contributing to alcoholic pancreatitis.
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PMID:Alcohol/cholecystokinin-evoked pancreatic acinar basolateral exocytosis is mediated by protein kinase C alpha phosphorylation of Munc18c. 1732 28

How therapeutic endoscopy has changed! As participants and observers of the evolution of endotherapy, one has to marvel at the progress we have made in this field. We have withstood mild outrage of our description of precut sphincterotomy, to questions regarding the efficacy of balloon dilators for the bile and pancreatic duct sphincters, to outspoken objections at national meetings of our presentations describing the use of pancreatic stents for the treatment of various forms of pancreatitis, to the expectation of greater progress and advancement in the field. We routinely drain pseudocysts, stent disrupted pancreatic ducts, but, now, we commend the innovators from Erasme Hospital in Brussels for their newly described technique of completing an endoscopic rendezvous procedure performed through an external pancreatic fistula (EPF). In this new technique, an endoscopist, who is observing the progress of a percutaneous puncture through an EPF, positions an endoscope in the stomach or small bowel lumen while assisting another endoscopist (not a radiologist) who is advancing catheters and guide wires through the fistulous tract (a virtual cyst demonstrated by EUS) so that the assistant can guide the operator's puncture through the gut wall into the bowel lumen in order to deploy an internal stent to allow the normal flow or egress of pancreatic juices into the gut facilitating the closure of the fistula. Although the procedure is time-consuming and probably not cost-effective for the free enterprise reimbursement system in the United States, the results of this procedure, in a small number of patients over a long time period, were as effective as surgery. Our hats are off to those who continue to explore the outer limits of endotherapy, and we look forward to more exciting, unquestioned developments in the field. This is progress.
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PMID:Endotherapy for pancreatic fistulae: inside out or outside in? 1733 45

The diagram of the mortality of acute pancreatitis is characterized by two distinct peaks, in a similar manner to other generalized acute inflammatory responses. In the first phase, which is characterized by "hyper-inflammatory" mechanisms, death occurs due to overwhelming SIRS and subsequent multi-organ failure. The second peak of death is usually detected much later, at least two weeks after the onset of acute pancreatitis. Infection in necrotising pancreatitis is frequently observed in this so-called "compensatory antiinflammatory" phase. Since there has been no effective therapy evolved to prevent the activation of inflammatory and proteolytic cascades, the treatment of acute pancreatitis is merely symptomatic. Adequate fluid resuscitation and analgesia are the mainstays of treatment. In case of development of multi-organ failure, extensive medical and ventilatory supportive therapy is usually necessary. However, recent studies suggested certain methods might decrease the incidence of infection in pancreatic necrosis, which is usually due to bacterial translocation from the gut. Numerous attempts have been published in the literature to decrease the frequency of septic complications. Furthermore, the outcome of studies favouring antibiotic prophylaxis in acute pancreatitis were debatable. The development of multi-resistant strains of Gram-positive bacteria and Candida, due to long-term antibiotic use, is a strong argument against the indication of prophylactic antibiotic use. Recently, various clinical studies aimed to decrease bacterial translocation, including probiotic use and enteral feeding as part of the treatment. This paper provides a systematic review on data available in the evidence based literature on the use of antibiotics and the role of alternative and supportive therapy in the treatment of severe acute pancreatitis.
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PMID:Preventive strategies for septic complications of acute pancreatitis. 1796 33

The neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) family of hormones exhibit a wide variety of biological actions on the mammalian gastrointestinal tract through known G-protein coupled receptor pathways. At least four receptor subtypes, denoted as Y(1), Y(2), Y(4) an Y(5), each with specific affinities to NPY ligands, serve as regulators of mucosal function, gastrointestinal motility and secretion. Investigations to date, however, have implicated the NPY peptides as mediators in the pathogenesis of numerous gastrointestinal disorders, including malabsorption, short gut, inflammatory bowel diseases, and forms of pancreatitis. Our understanding of these diseases and the interactions of NPY peptides have been advanced by the development of receptor agonists and antagonists that can be used experimentally in animal models. Potent selective PYY agonists have been developed that exhibit clinical potential as proabsorptive agents. NPY receptor agonists and antagonists as well as mice harboring null mutations in the Y(1) and Y(4) receptors have provided novel approaches in preventing intestinal inflammation and diarrhea. The use of competitive antagonists and Y(2) receptor knockouts have also aided in understanding secretory tone and electrogenic ion transport in the colon. In the pancreas, PYY suppresses amylase and cytokine release, which would be desirable in the clinical therapy of pancreatitis. Protein/DNA array analysis has revealed that PYY reduces transcription factor binding activity and disrupts signal transduction pathways activated by TNF-alpha in acinar cells. The present review gives an overview of NPY research in gastrointestinal disease and discusses its clinical relevance and potential use as therapy.
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PMID:NPY family of hormones: clinical relevance and potential use in gastrointestinal disease. 1797 80

Ectopic pancreatic tissues of the gut are usually found incidentally during laparotomy or are reported in the autopsy findings. Rarely these ectopic pancreatic tissues may cause symptoms such as hemorrhage, pancreatitis, intussusception or perforation. We present a case report of the presence of multiple ectopic pancreatic tissues in the gut causing hemorrhage and perforation in a preterm, extremely low birth weight neonate with multiple congenital anomalies.
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PMID:Intestinal perforation by multiple ectopic pancreatic tissues in a neonate with multiple congenital anomalies. 1838 11

The time-related metabolic responses to l-arginine (ARG)-induced exocrine pancreatic toxicity were investigated using single ip doses of 1,000 and 4,000 mg/kg body weight over a 7 day experimental period in male Sprague-Dawley rats. Sequential timed urine and plasma samples were analyzed using high resolution (1)H NMR spectroscopy together with complementary clinical chemistry and histopathology analyses. Principal components analysis (PCA) and orthogonal projection on latent structures discriminant analysis (O-PLS-DA) were utilized to analyze the (1)H NMR data and to extract and identify candidate biomarkers and to construct metabolic trajectories post ARG administration. Low doses of ARG resulted in virtually no histopathological damage and distinct reversible metabolic response trajectories. High doses of ARG caused pancreatic acinar degeneration and necrosis and characteristic metabolic trajectory profiles with several distinct phases. The initial trajectory phase (0-8 h) involved changes in the urea cycle and transamination indicating a homeostatic response to detoxify excess ammonia generated from ARG catabolism. By 48 h, there was a notable enhancement of the excretion of the gut microbial metabolites, phenylacetylglycine (PAG), 4-cresol-glucuronide and 4-cresol-sulfate, suggesting that compromised pancreatic function impacts on the activity of the gut microbiota giving potential rise to a novel class of surrogate extragenomic biomarkers of pancreatic injury. The implied compromise of microbiotal function may also contribute to secondary hepatic and pancreatic toxic responses. We show here for the first time the value of metabonomic studies in investigating metabolic disruption due to experimental pancreatitis. The variety of observed systemic responses suggests that this approach may be of general value in the assessment of other animal models or human pancreatitis.
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PMID:Temporal metabonomic modeling of l-arginine-induced exocrine pancreatitis. 1871 Feb 74

Of all the body systems, the gastrointestinal (GI) tract is the most exposed to proteinases. Proteolytic activity must thus be tightly regulated in the face of diverse environmental challenges, because unrestrained or excessive proteolysis leads to pathological GI conditions. The protease-activated receptor-2 (PAR-2) is expressed in numerous cell types within the GI tract, suggesting both multiple functions and numerous modes of receptor activation. Although best known as a pancreatic digestive enzyme, trypsin has also been found in other tissues and various cancers. Of interest, trypsin and PAR-2 act together in an autocrine loop that promotes proliferation, invasion and metastasis in neoplasia through various mechanisms. Trypsin and PAR-2 seem to act both directly and indirectly through activation of other proteinase cascades, including metalloproteinases. PAR-2 activation can participate in inflammatory reactions, be protective to mucosal surfaces, send or inhibit nociceptive messages, modify gut motility or secretory functions, and stimulate cell proliferation and motility. Several studies point to a role for the PARs in disease processes of the GI tract and pancreas ranging from inflammatory bowel disease, symptoms associated with irritable bowel syndrome, pain in pancreatitis, development of colon and other GI cancers, and even infectious colitis. Proteinases should not only be considered from the traditional view as digestive or degradative enzymes in the gut, but additionally as signalling molecules that actively participate in the spectrum of physiology and diseased states of the GI tract.
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PMID:Proteinase-activated receptor 2 (PAR-2) in gastrointestinal and pancreatic pathophysiology, inflammation and neoplasia. 1908 62

The purpose of this paper is to investigate the rate of translocation of Escherichia coli strains in different experimental/animal models. Four proficient translocating E. coli strains isolated from mesenteric lymph nodes (MLNs) and/or the blood of rats (strains KIC-1 and KIC-2), from a fatal case of pancreatitis (HMLN-1) and from pigs (PC-1 isolated in this study) were tested for their ability to translocate across two host species and the Caco-2 cell line as a model of the human gut epithelium. HMLN-1 was found in the MLNs of all 15 pigs tested. This strain, however, did not translocate in any rats and only colonised the caecum of four rats in small numbers. HMLN-1 and PC-1 were the dominant translocating strains in Caco-2 cells compared to KIC-1 and KIC-2, which were found to translocate at a lower rate in pigs and in Caco-2 cells. The rate of translocation of PC-1 in rats was also very low compared to KIC-1 and KIC-2. We suggest that, in studies aiming to investigate the mechanism of translocation of E. coli strains isolated from humans, rats may not be an appropriate animal model and that the Caco-2 cells or pigs are more suitable in vitro and in vivo models, respectively.
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PMID:Host species-specific translocation of Escherichia coli. 1943 50


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