Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular mechanisms associated with apoptosis in pancreas remain largely unknown. Clusterin mRNA is induced in several tissues in response to most apoptotic stimuli. In these tissues, clusterin has an antiapoptotic activity. The aim of this work was to test whether clusterin, which is not expressed in normal pancreas, was induced in pancreas during pancreatitis and pancreatic development. Clusterin mRNA levels were strongly increased 6 h after pancreatitis induction. Maximal expression happened between 24-48 h and decreased progressively to undetectable levels at day 5. Clusterin mRNA was expressed with similar intensity in oedematous caerulein-induced pancreatitis and in response to various degrees of necrohaemorrhagic taurocholate-induced pancreatitis, indicating a maximal gene activity in all types of pancreatitis; in situ hybridization showed that the acinar cells and some ducts expressed clusterin mRNA. A single band of about 35-38 kDa was detected by western blot in pancreatic homogenates and in pancreatic juice from rats with acute pancreatitis, but not from control rats. Clusterin mRNA expression was strong in late fetal life and remains high until day 11 post-partum, then decreased progressively with a minimum from 35 to 90 days post-partum. Clusterin mRNA levels were strongly induced in pancreatic acinar AR4-2J cells in response to various apoptotic stimuli (i.e., cycloheximide, staurosporine, ceramide and H2O2) but not with interleukin (IL)-1, IL-4 or IL-6 or heat shock, which do not induce apoptosis in AR4-2J cells. In conclusion, we demonstrated that clusterin is synthesized and released by the pancreas. Its strong expression during acute pancreatitis suggests its involvement in the pancreatic response to injury. Clusterin is also induced during pancreatic development. Because these situations are associated with apoptosis and clusterin was shown to protect against apoptosis, we speculate that clusterin could be involved in the control of acinar cell apoptosis.
 ...
PMID:Clusterin overexpression in rat pancreas during the acute phase of pancreatitis and pancreatic development. 966 Jan 81

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.
 ...
PMID:Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis. 972 66

We studied potential indicators of severe acute pancreatitis by measuring the blood concentrations of various cytokines, polymorphonuclear leucocyte elastase (PMN-E), acute phase reactants, pancreatic amylase (P-AMY), pancreatic elastase-1 (E-1) and white blood cell (WBC) counts in patients with acute pancreatitis. In addition, the presence of multiple organ damage was assessed. Subjects consisted of 22 patients with acute pancreatitis including severe (n = 11), moderate (n = 4) and mild (n = 7) cases. A significant positive correlation was observed between the number of organs damaged and the peak concentrations of interleukin (IL)-6, PMN-E, C-reactive protein (CRP) and pancreatic secretory trypsin inhibitor (PSTI). Among these markers, blood concentrations of PMN-E and IL-6 rapidly increased and peaked at the early phase of acute pancreatitis whereas CRP and PSTI did not. The elevation of PMN-E and IL-6 was greater the more severe the symptoms. However, no significant correlation was observed between the number of organs damaged and the maximum serum concentrations of P-AMY and E-1, or the WBC count, which have been considered to be markers of pancreatitis. These results suggest that PMN-E and IL-6 concentrations are useful indicators of severity and prognosis and their determination facilitates the selection of appropriate treatment in the early stages of disease to prevent the aggressive progression of acute pancreatitis.
 ...
PMID:Blood concentrations of polymorphonuclear leucocyte elastase and interleukin-6 are indicators for the occurrence of multiple organ failures at the early stage of acute pancreatitis. 991 21

We evaluated the behavior of sera interleukin p70 (IL-12p70) and IL-12p40 in patients with acute pancreatitis. Twenty-three acute pancreatitis patients were studied (12 had severe pancreatitis and 11 had mild pancreatitis). Twenty healthy subjects were studied as controls. Serum concentrations of total IL-12, IL-12p70, IL-12p40, and IL-6 were determined in all subjects on admission to the hospital; in patients with acute pancreatitis, the serum levels of these molecules also were determined for the 5 days after admission. Acute pancreatitis patients had serum concentrations of total IL-12, IL-12p40, and IL-6 significantly higher (p < 0.05) than those of the healthy subjects from the first to the sixth day of the study; serum concentrations of IL-12p70 were significantly higher in acute pancreatitis patients (p < 0.02) than in the healthy subjects on the first of the disease and significantly lower (p < 0.05) on the second, third, and fourth days of illness. Reduction of IL-12p70 in acute pancreatitis patients was not due to a failure of the monocytes because the production of IL-6 was increased. Increased amounts of IL-12p40 in acute pancreatitis patients may be responsible for their increased susceptibility to infection.
 ...
PMID:Behavior of serum interleukin 12 in human acute pancreatitis. 1020 82

During the last few years attention has been focused on an important role of inflammatory mediators in the pathophysiology and systemic complications of acute pancreatitis. The present study deals with those of the mediators which have shown demonstrable activity in the course of pancreatitis, e.g. acute-phase proteins (among others C-reactive protein and alpha-1-antitrypsin) and neutrophil elastase (PMN-elastase) as the marker for granulocyte activity. The activity of cytokines IL-6, IL-8 and IL-1, of alpha-cachectin (TNF alpha), as well as of the platelet-activating factor (PAF) and the trypsinogen activation peptide (TAP), was discussed.
 ...
PMID:[Inflammatory mediators in the acute pancreatitis]. 1033 84

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.
 ...
PMID:Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome. 1039 Mar 90

To clarify the role of cytokines and acinar cell apoptosis in the pathogenesis of acute pancreatitis, we investigated the expression of intrapancreatic cytokines and apoptosis-related molecules in mice after pancreatic duct ligation (PDL). From day 1 or 3 after PDL, the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor (TNF-alpha) mRNA were up-regulated in the pancreas, suggesting that these cytokines may be involved in the development of pancreatitis after PDL. Acinar cell apoptosis was observed in the pancreas at rates of 0.13 +/- 0.03, 1.32 +/- 0.38, and 0.86 +/- 0.23% on days 1, 3, and 7 after PDL, respectively. Significant increases in intrapancreatic mRNA levels of TNF-alpha, Fas ligand (FasL), and IL-1beta-converting enzyme (ICE) were observed from day 3 after PDL with the appearance of acinar cell apoptosis. The serum amylase activity peaked on day 1 after PDL and gradually decreased on days 3 and 7 after PDL. These results suggest that acinar cell apoptosis induced after PDL may modulate the progression of acute pancreatitis by reducing the release of digestive enzymes and may therefore be a host defense mechanism, and that acinar cell apoptosis after PDL may be mediated by the TNF-alpha and/or Fas/FasL and ICE system.
 ...
PMID:Cytokine expression and induction of acinar cell apoptosis after pancreatic duct ligation in mice. 1043 65

Recently, there has been a great deal of interest in the role of cytokines in acute pancreatitis. Serum levels of IL-1, IL-6, and TNF-alpha have been demonstrated to be elevated in acute pancreatitis. We hypothesized that cytokines may be produced primarily by pancreatic parenchymal cells. Reasoning that ductal epithelium is the cell type most likely to be exposed to noxious stimuli in common causes of pancreatitis, such as ERCP and passage of a gallstone, we examined the response of well differentiated pancreatic ductal adenocarcinoma cell lines to stimuli known to stimulate cytokine production in other cells. CAPAN-1 and CAPAN-2 cells were incubated with endotoxin or TNF-alpha. The supernatant was assayed for production of IL-1, IL-6, and IL-8 by ELISA. The cells were assayed for activation of the transcription factor NF-kappaB by electrophoretic mobility shift assay. There was no detectable production of IL-1 by either cell line. CAPAN-1 cells had concentration-dependent production of IL-6 and IL-8 in response to both endotoxin and TNF-alpha. CAPAN-2 cells had concentration-dependent production of IL-6 and IL-8 in response to TNF-alpha. They had low level expression of IL-8 that was unaffected by any concentration of LPS, and no detectable production of IL-6 in response to LPS. These findings suggest that pancreatic duct cells may take an active part in the pathogenesis of acute pancreatitis through the production of cytokines.
 ...
PMID:Cytokine production by CAPAN-1 and CAPAN-2 cell lines. 1079 56

Acute pancreatitis is a disorder that has numerous causes and an obscure pathogenesis. Bile duct stones and alcohol abuse together account for about 80% of acute pancreatitis. Most episodes of biliary pancreatitis are associated with transient impaction of the stone in the ampulla (that causes obstruction of the pancreatic duct, with ductal hypertension) or passage of the stone though and into the duodenum. Other causes of acute pancreatitis are various toxins, drugs, other obstructive causes (such as malignancy or fibrotic sphincter of Oddi), metabolic abnormalities, trauma, ischemia, infection, autoimmune diseases, etc. In 10% of cases of acute pancreatitis, no underlying cause can be identified; this is idiopathic pancreatitis. Occult biliary microlithiasis may be the cause of two thirds of the cases of "idiopathic" acute pancreatitis. Intra-acinar activation of trypsinogen plays a central role in the pathogenesis of acute pancreatitis, resulting in subsequent activation of other proteases causing the subsequent cell damage. Ischemia/reperfusion injury is increasingly recognized as a common and important mechanism in the pathogenesis of acute pancreatitis and especially in the progression from mild edematous to severe necrotizing form. Increased intracellular calcium concentration also mediates acinar cell damage. Oxygen-derived free radicals and many cytokines (e.g., interleukin [IL]-1, IL-6, IL-8, tumor necrosis factor-alpha, platelet activating factor) are considered to be principal mediators in the transformation of acute pancreatitis from a local inflammatory process into a multiorgan illness.
 ...
PMID:Etiology and pathogenesis of acute pancreatitis: current concepts. 1087 61

We investigated the effects of nafamostat mesilate, a synthetic protease inhibitor clinically used for patients with pancreatitis or disseminated intravascular coagulopathy, on NO synthesis and apoptosis in lipopolysaccharide (LPS)-treated human trophoblasts. Nafamostat mesilate or aminoguanidine, an inhibitor of NO synthase, suppressed NO synthesis and apoptosis in trophoblasts induced by LPS. Both agents also suppressed matrix metalloproteinase-2 activity induced by LPS. LPS also stimulated secretion of IL-6 and IL-8 in cultured trophoblasts, which was suppressed by nafamostat mesilate. Protease inhibitors including nafamostat mesilate may be therapeutic agents for chorioamnionitis and various diseases including septic shock, ischemia-reperfusion injury in brain and heart, graft rejection, and acute phase inflammatory diseases, in which overproduction of NO or peroxynitrite is involved in tissue injury.
 ...
PMID:Nafamostat mesilate, a serine protease inhibitor, suppresses lipopolysaccharide-induced nitric oxide synthesis and apoptosis in cultured human trophoblasts. 1095 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>