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)

Infected pancreatic necrosis (IPN), the most severe form of acute pancreatitis, is responsible for most cases of pancreatitis-related morbidity and mortality. Since 1986, 220 patients with IPN have been treated. The surgical treatment was performed on average 18.5 days (range, 8-25 days) after the onset of acute pancreatitis and consisted of wide-ranging necrosectomy, combined with widespread drainage and continuous lavage. In 108 of the 220 cases, some other surgical intervention (distal pancreatic resection, splenectomy, total pancreatectomy, cholecystectomy, colon resection, etc.) was also performed. Following surgery, the supportive therapy consisted of immunonutrition (glutamine and arginine supplementation) and modification of cytokine production with pentoxifylline and dexamethasone. Continuous lavage was applied for an average of 44.5 days (range, 21-95 days), with an average of 9.5 L (range, 5-20 L) of saline per day. The bacteriologic findings revealed mainly enteral bacteria, but Candida infection was also frequently detected (21%). Forty-eight patients (22%) had to undergo reoperation. The overall hospital mortality was 7.7% (17 patients died). In our experience, IPN responds well to adequate surgical treatment, continuous, longstanding widespread drainage and lavage, together with supportive therapy consisting of immunonutrition and modification of cytokine production, combined with adequate antibiotic and antifungal medication.
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PMID:Surgical management and complex treatment of infected pancreatic necrosis: 18-year experience at a single center. 1645 62

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

Pancreatitis-associated protein I (PAP I), also known as HIP, p23, or Reg2 protein, has recently been implicated in the endogenous regulation of inflammation. Although it was initially characterized as a protein that is overexpressed in acute pancreatitis, PAP I has also been associated with a number of inflammatory diseases, such as Crohn's disease. Knowing that PAP I and IL-10 responses share several features, we have used a pancreatic acinar cell line (AR42J) to assess the extent to which their expression is reciprocally regulated, and whether the JAK/STAT and NF-kappaB signaling pathways are involved in the suppression of inflammation mediated by PAP I. We observed that PAP I is induced in epithelial cells by IL-10 and by PAP I itself. In contrast, we found phosphorylation and nuclear translocation of STAT3 and induction of suppressor of cytokine signaling 3 in response to PAP I exposure. Finally, a JAK-specific inhibitor, tyrphostin AG490, markedly prevented PAP I-induced NF-kappaB inhibition, pointing to a cross-talk between JAK/STAT3 and NF-kappaB signaling pathways. Together, these findings indicate that PAP I inhibits the inflammatory response by blocking NF-kappaB activation through a STAT3-dependent mechanism. Important functional similarities to the anti-inflammatory cytokine IL-10 suggest that PAP I could play a role similar to that of IL-10 in epithelial cells.
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PMID:Pancreatitis-associated protein I suppresses NF-kappa B activation through a JAK/STAT-mediated mechanism in epithelial cells. 1651 47

Adenocarcinoma of the exocrine pancreas is the fourth leading cause of cancer-related death in men and women in the U.S. Cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. We analyzed cytokine gene polymorphisms as risk factors for pancreatic cancer using questionnaire data obtained by in-person interviews and germ line DNA collected in a population-based case-control study of pancreatic cancer (532 cases and 1,701 controls) conducted in the San Francisco Bay Area. We used mass spectrometry and gel-based methods to genotype 308 cases and 964 population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression analysis and included adjustment for age, sex, and smoking. We assessed potential interactions between these polymorphisms, proinflammatory conditions (e.g., pancreatitis, ulcer, and obesity), and smoking as risk factors for pancreatic cancer. There was no overall association between pancreatic cancer risk and tumor necrosis factor-alpha (TNF-A -308G/A), regulated upon activation, normally T cell-expressed, and presumably secreted (RANTES -403G/A), and CC chemokine receptor 5 (CCR5-Delta32) polymorphisms. There was a nearly 7-fold increased relative risk estimate for pancreatic cancer in individuals with a history of pancreatitis (adjusted OR, 6.9; 95% CI, 3.4-14.1). Among patients with pancreatic cancer, pancreatitis was significantly associated with TNF-A -308 GA + AA (OR, 3.1; 95% CI, 1.3-7.4) and with RANTES -403 GA + AA (OR, 2.3; 95% CI, 1.0-5.4). There was evidence for a possible interaction between current active smoking and CCR5-32del. Our results lend support for the hypothesis that proinflammatory gene polymorphisms, in combination with proinflammatory conditions, may influence the development of pancreatic cancer.
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PMID:Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma. 1661 15

Myofibroblasts and cytokines such as transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor (PDGF)-B have been found to play an important role in pancreatitis-associated fibrogenesis. It is still unclear, however, where in the inflamed pancreas and when these fibrogenic cells and cytokines can be detected. In this study we examined pancreatic tissue from patients with alcoholic chronic pancreatitis to determine the localization and distribution of myofibroblasts and the expression of cytokines in relation to the tissue damage and the activity of the inflammatory process. In tissue from pancreatic specimens from 59 patients with alcoholic chronic pancreatitis the inflammatory process was histologically staged. Myofibroblasts and the cytokines latency-associated peptide, a TGF-beta propeptide, TGF-beta receptor II, PDGF-B and the alpha-isoform of the PDGF receptor were immunohistochemically identified in 10 selected cases representing the four defined stages of alcoholic chronic pancreatitis. In stage I, the stage with overt tissue injury, myofibroblasts were numerous and especially associated with macrophages around areas of necrosis. In stage II, the stage with cellular fibrosis, myofibroblasts were the main component of the interlobular tissue. In stage III, the stage with dense fibrosis, myofibroblasts were rare, and in stage IV, when calculi were present, myofibroblasts were only detected adjacent to duct ulcerations caused by calculi. Latency-associated peptide and TGF-beta receptor II as well as PDGF-B and PDGF receptor-alpha were mainly expressed by macrophages, myofibroblasts and epithelial cells in stages I and II. The results suggest that the fibrogenic process in alcoholic chronic pancreatitis is initiated by a cytokine-based interplay of macrophages and myofibroblasts that follows tissue injury.
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PMID:Fibrogenesis in alcoholic chronic pancreatitis: the role of tissue necrosis, macrophages, myofibroblasts and cytokines. 1668 Jan 57

The number of hospitalizations in children with acute and chronic pancreatitis is increasing and accounts for significant morbidity. Acute pancreatitis is a reversible event involving diffuse inflammation of the pancreas with variable involvement of other regional tissues, remote organs, or both, whereas chronic pancreatitis is a process that produces irreversible changes in the pancreatic structure and function. Mutations in the gene encoding cationic trypsinogen have recently been identified to be associated with hereditary pancreatitis. Genetic mutations in the pancreatic secretory trypsin inhibitor and the cystic fibrosis transmembrane conductance regulator have been described to play a role in the development of pancreatitis as well. Mutations in the cytokine target genes relating to regulation of inflammation are likely to be important in determining the severity of pancreatitis. These findings, along with the advances in cell biology, have contributed to a better understanding of the pathophysiology of pancreatic diseases.
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PMID:Genetic issues in pediatric pancreatitis. 1676 92

The aim of this study was to investigate the influence of omega-3 fatty acids (omega3FA) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increases in mortality rate, intestinal permeability, bacterial infection in pancreas and extrapancreatic organs, and serum activity of urea and amylase, alanine transferase (ALT), interleukin (IL)-6, tumor necrotizing factor-alpha (TNF-alpha), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and a considerable decrease of concentrations of calcium, protein and albumin. The use of omega3FA reduced mortality, phenol sulfophthalein excretion in urine, bacterial infection in pancreas, liver, spleen, MPO and MDA levels in pancreatic and lung tissue, LDH level in BAL fluid and serum IL-6 and TNF-alpha values. Serum triglyceride increased only in the omega3FA groups. Serum amylase, ALT, calcium, urea, protein, IL-1, and degree of pancreatic damage indicated no difference between the pancreatitis groups. Increased intestinal permeability and cytokine levels, and free radical damage play an important role during the course of acute pancreatitis. The treatment with omega3FA improves these effects. omega3FA may be useful in the treatment during ANP in rats. Therefore, it can be beneficial in patients with pancreatitis.
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PMID:Effects of omega-3 fatty acids on acute necrotizing pancreatitis in rats. 1678 30

Efforts to unravel the intracellular processes that occur in acute pancreatitis continue. In cerulein pancreatitis, new evidence supports the idea that a very early event is premature trypsinogen activation triggered by lysosomal cathepsin B. Clinicians persist in trying to identify more sensitive and specific prognostic signs of the severity of attacks of pancreatitis; one study suggests that computer-based neural networks may be an alternative to biochemical markers and clinical scoring systems. The systemic severity of episodes of pancreatitis seems to be related to a multitude of proinflammatory cytokines and chemokines acting at sites distant from the pancreas. Selective blockade of some of these peptides (eg, endothelin-1 and platelet-activating factor) has decreased mortality and distant organ damage in animal models and may deserve clinical evaluation. Gene therapy may be more efficient than pharmacologic therapy in increasing anti-inflammatory cytokine (interleukin-10) levels. Clinical studies have further underlined the usefulness of prophylactic antibiotics in severe acute pancreatitis. Radiologic and endoscopic techniques may be alternatives to surgery for certain complications of pancreatitis (eg, infected necrosis and pseudocysts) in particular subsets of patients.
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PMID:Acute pancreatitis. 1702 79

Pancreatic stellate cells (PSC) are crucially involved in the development of fibrosis, a hallmark of chronic pancreatitis. Therefore, PSC represent an attractive target for the modulation of cellular functions providing the prerequisite for the establishment of novel therapeutic strategies like transfer of genetic material to the cells. Based on recent studies suggesting that the chronic course of pancreatitis is associated with immune deviation towards a Th1 cytokine profile, we have investigated the applicability of primary PSC to an adenovirus-mediated transfer of the cDNA encoding the Th2 cytokine interleukin (IL) 4 and the autocrine-acting effects of IL 4 on the cells in vitro. The transduction of primary PSC with a replication-incompetent adenovirus type 5 vector carrying the cDNA encoding rat IL- 4 resulted in a distinct expression of the cytokine on mRNA and protein level for two weeks. Similar to recombinant IL 4, effects of the endogenously synthesized cytokine were mediated by the signal transducer and activator of transcription (STAT)6. Interestingly, beside the increase of PSC proliferation, IL 4 transduction was accompanied by an up-regulation in the endogenous expression of the anti-inflammatory cytokine IL 10. In summary, our data suggest that PSC are suitable targets for gene therapy modulating cellular interactions in the pancreas.
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PMID:Adenovirus-mediated gene transfer of interleukin-4 into pancreatic stellate cells promotes interleukin-10 expression. 1712 92

Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-related function has not been reported yet. Then, it was demonstrated that PAP expression may be activated in some tissues in a constitutive or injury- and inflammation-induced manner. More recently, it has been found that PAP acts as an anti-inflammatory factor in vitro and in vivo. PAP expression can be induced by several pro- and anti-inflammatory cytokines and by itself through a JAK/STAT3-dependent pathway. PAP is able to activate the expression of the anti-inflammatory factor SOCS3 through the JAK/STAT3-dependent pathway. The JAK/STAT3/SOCS3 pathway seems to be a common point between PAP and several cytokines. Therefore, it is reasonable to propose that PAP is a new anti-inflammatory cytokine.
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PMID:Pancreatitis-associated protein: from a lectin to an anti-inflammatory cytokine. 1722 96


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