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)

The osmolality of contrast injected retrograde into the rat pancreatic duct did not affect the severity of the pancreatitis (Urografin, 1,300 mOsm/kg, and Hexabrix, 580 mOsm/kg). The severity of the pancreatitis induced in rats was assessed by survival rate, histologic grading, wet lung ratio, and serum levels of amylase, lipase, and trypsin-like activity. Rats with pancreatitis induced by retrograde injected Urografin, lipopolysaccharide, taurocholic acid plus enterokinase were treated with either intravenous (i.v.) FUT-175 (Nafamstat Mesilate), FUT-175 administered by retrograde pancreatic injection, i.v. terbutaline, i.v. piperacillin sodium, piperacillin sodium by retrograde pancreatic duct injection, or a combination of FUT-175 plus terbutaline and piperacillin. Survival among the rats was increased and the incidence of pancreatic infection reduced in rats treated with i.v. piperacillin or with a combination of FUT-175 plus i.v. terbutaline, plus i.v. piperacillin compared to controls.
 ...
PMID:Therapeutic regimens in acute experimental pancreatitis in rats: effects of a protease inhibitor, a beta-agonist, and antibiotics. 747 69

The protective effects of a neutrophil elastase inhibitor (ONO-5046) on cerulein-induced pancreatitis followed by a septic challenge with intraperitoneal lipopolysaccharide (LPS) were studied in a rat model. Pancreatitis was induced by four intramuscular injections of cerulein (50 micrograms/kg at 1-hr intervals). ONO-5046 was administered by continuous intravenous infusion via the right jugular vein (50 mg/kg/hr, 30 min prior to the first cerulein injection to 20 hr following the last cerulein injection). Significant differences in serum amylase and pancreatic wet weight ratio were not observed between the animals with pancreatitis treated with or without ONO-5046. There was no significant difference in the in vitro tumor necrosis factor-alpha (TNF-alpha) production by peritoneal macrophages from rats with pancreatitis treated with or without ONO-5046. In a second experiment, LPS (10 mg/kg) was administered intraperitoneally as the septic challenge 6 hr following the first cerulein injection. Lung hemorrhage was seen in the animals with pancreatitis untreated with ONO-5046 24 hr following the first cerulein injection. No significant lung hemorrhage was observed in the animals with pancreatitis treated with ONO-5046 administering 30 min prior to the first cerulein injection. These results suggest that lung hemorrhage in cerulein-induced pancreatitis that follows a septic challenge with LPS can be prevented by the intravenous administration of ONO-5046. Thus there is a significant role for neutrophil elastase in pancreatitis-associated lung injury.
 ...
PMID:Neutrophil elastase inhibitor (ONO-5046) prevents lung hemorrhage induced by lipopolysaccharide in rat model of cerulein pancreatitis. 758 85

The cytokines such as tumor necrosis factor and interleukin-1 secreted from macrophages/monocytes proved to play important roles in the pathogenesis of endotoxemia, severe pancreatitis and other surgical injuries. However, it is still unclear how inhalational anesthetic agents influence the secretion of these cytokines from macrophages/monocytes. We investigated the effects of isoflurane on TNF-alpha and IL-1 beta secretions from human peripheral blood monocytes stimulated by lipopolysaccharide. TNF-alpha and IL-1 beta secretions increased after LPS stimulation and this increase was inhibited by isoflurane in dose-dependent fashion. The inhibitory action of isoflurane disappeared between 1 and 3 hours after stopping isoflurane inhalation. We concluded that isoflurane could inhibit TNF-alpha and IL-1 beta secretions from peripheral blood monocytes stimulated by LPS in a dose-dependent fashion and that the inhibitory action of isoflurane was reversible.
 ...
PMID:[The effect of isoflurane on the secretion of TNF-alpha and IL-1 beta from LPS-stimulated human peripheral blood monocytes]. 763 87

Severe acute pancreatitis is often complicated by intraperitoneal infection, resulting in multiple organ failure (MOF). It is known to elevate serum tumor necrosis factor (TNF-alpha) in patients with sepsis and/or MOF. In order to study the role of TNF-alpha in the aggravation of acute pancreatitis, we investigated TNF-alpha production by peritoneal macrophages in acute pancreatitis rat using the cerulein-induced pancreatitis model. TNF-alpha production by isolated peritoneal macrophages following lipopolysaccharide (LPS) stimulation was significantly increased in pancreatitis rats as compared with nonpancreatitis control rats (p < 0.001). Serum TNF-alpha activity was elevated following intraperitoneal administration of LPS as the septic challenge both in pancreatitis rats and in control rats, being significantly higher in the former (p < 0.05). Histological findings and liver function tests revealed that LPS induced more severe liver damage in pancreatitis rats than in control rats within 24 h after LPS administration. These results indicate that increased TNF-alpha production by peritoneal macrophages in acute pancreatitis augmented LPS-induced liver injury and suggest the possibility that TNF-alpha may play a role in the development of MOF during acute pancreatitis complicated by intraabdominal sepsis.
 ...
PMID:The role of tumor necrosis factor-alpha in the aggravation of cerulein-induced pancreatitis in rats. 828 75

Intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 50 micrograms/kg increased the activity and the mRNA level of manganese superoxide dismutase (Mn-SOD) but did not change those of copper/zinc-SOD (Cu/Zn-SOD) in the rat pancreas. Both the formation of pancreatic edema and the elevation of serum amylase during caerulein pancreatitis were significantly relieved in the rats pretreated with LPS (50 micrograms/kg) compared with the rats without the pretreatment. These results support the view that superoxides play a key role in the pathogenesis of caerulein pancreatitis, and that Mn-SOD in the pancreas may work as a defense against the development of this disease.
 ...
PMID:Lipopolysaccharide induces manganese superoxide dismutase in the rat pancreas: its role in caerulein pancreatitis. 855 79

The effects of pancreatic secretory trypsin inhibitor (PSTI) on cerulein-induced pancreatitis were studied in a rat model. Arg44 of PSTI was replaced by Ser using site-directed mutagenesis (R44S-PSTI). R44S-PSTI has a longer half-life than the natural form. Pancreatitis was induced by four intramuscular injections of cerulein (50 microgram/kg at 1 h intervals). Continuous intravenous infusion of R44S-PSTI began at a dose of 20 micrograms/kg/h 30 min before the first cerulein injection, and was completed 3 h after the last cerulein injection. Tumour necrosis factor (TNF-alpha) production by isolated peritoneal macrophages from rats with cerulein-induced pancreatitis increased following lipopolysaccharide stimulation, compared to control rats (P < 0.01). R44S-PSTI administration significantly decreased the TNF-alpha production by peritoneal macrophages from rats with cerulein-induced pancreatitis (P < 0.05). In addition, R44S-PSTI significantly reduced serum amylase activity (P < 0.01) and pancreatic wet weight after pancreatitis induction (P < 0.05). Histological examination revealed marked acinar cell vacuolization, interstitial oedema, and cellular infiltration in cerulein-induced pancreatitis, but a lesser degree of histological change in rats that were treated with R44S-PSTI. Prophylactic use of intravenous R44S-PSTI infusion may reduce the severity of acute pancreatitis either histologically or serologically.
 ...
PMID:The protective effects of long-acting recombinant human pancreatic secretory trypsin inhibitor (R44S-PSTI) in a rat model of cerulein-induced pancreatitis. 867 1

The role of the hypothalamic-pituitary-adrenal axis (HPA axis) in acute pancreatitis has not yet been clarified. In the present study, the concentrations of serum corticosterone and amylase, the severity of pancreatic edema, and the histology of the pancreas during cerulein-induced pancreatitis were compared in two strains of rats whose HPA axes have been reported to be hyperresponsive (Fischer female) and hyporesponsive (Lewis female) to inflammatory mediators. First, we confirmed that the secretory response of corticosterone to lipopolysaccharide was remarkably blunted in Lewis rats compared with Fischer rats. With a single intraperitoneal injection of cerulein at a dose of 50 micrograms/kg, the serum corticosterone of Fischer rats increased promptly, and their serum levels were significantly higher than those of Lewis rats at all points after the induction of pancreatitis. The edema formation and infiltration of inflammatory cells into the pancreas were more severe in Lewis rats than in Fischer rats. The serum amylase concentration was not significantly different between the two strains, except at 2 h after the induction of pancreatitis. The in vitro study using dispersed pancreatic acini showed that there was no significant difference in cerulein-stimulated amylase secretion between the two strains. These findings suggest that the responsiveness of the HPA axis and the consequent secretion of glucocorticoids might modify the pathological features of acute pancreatitis.
 ...
PMID:The role of pituitary-adrenal counterregulation of inflammation in cerulein-induced pancreatitis: a comparison between Fischer and Lewis rats. 883 Mar 35

Nitric oxide (NO) has been shown to play a significant role in inflammation. To clarify the role of NO in acute pancreatitis, we investigated the serum concentrations of NO chi (NO2- plus NO3-) and tumor necrosis factor-alpha (TNF-alpha) and the grade of pancreatitis in cerulein-induced pancreatitis in mice pretreated with lipopolysaccharide (LPS) or not. LPS pretreatment aggravated the cerulein pancreatitis in association with a transient increase in serum TNF-alpha, which was followed by a gradual elevation of serum NO chi. This elevation of serum NO chi concentration was inhibited by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA). In addition, the activity of NADPH-diaphorase (NADPH-d), a marker for NO synthase, appeared in the peritoneal macrophages of LPS-pretreated mice after the induction of pancreatitis. No elevation of serum NO chi or appearance of NADPH-d activity in peritoneal cells was found in mice without LPS pretreatment. Administration of L-NNA enhanced the elevation of pancreatitis-induced serum amylase in mice untreated with LPS, while L-NNA inhibited the elevation in LPS-pretreated mice. The effects of L-NNA were reversed by the administration of L-arginine but were not affected by D-arginine. These results suggested that (a) inflammatory cells may not be fully activated to produce excessive NO in uncomplicated edematous pancreatitis, and (b) edematous pancreatitis may be aggravated by excessively produced NO if bacterial infection is complicated and inflammatory cells are activated to express inducible NO synthase.
 ...
PMID:The role of nitric oxide in mouse cerulein-induced pancreatitis with and without lipopolysaccharide pretreatment. 892 22

The role of bronchoalveolar macrophages (BAMs) in the aggravation of cerulein-induced pancreatitis was studied by measuring expression of cytokine-induced neutrophil chemoattractant (CINC) in vitro. Pancreatitis was induced by four intramuscular injections of cerulein (50 microg/kg at 1-hr intervals). Pancreatitis rats were injected intraperitoneally with 30 mg/kg lipopolysaccharide (LPS) 6 hr following the first cerulein injection as a septic challenge. Rats were divided into four groups: group I, nonpancreatitis without LPS; group II, pancreatitis without LPS; group III, nonpancreatitis with LPS; and group IV, pancreatitis with LPS. Hyperactivity of BAMs in response to LPS was assessed as a function of in vitro CINC production. CINC concentrations of the serum and bronchoalveolar lavage fluid in group IV were significantly higher than those in groups I, II, and III. BAMs in group II harvested 6 hr following the first cerulein injection had significantly greater CINC production than those in group I. Northern blot analysis revealed abundant CINC mRNA transcripts in BAMs from groups III and IV. Additionally, myeloperoxidase activity in the lung of group IV rats 8 and 12 hr following the first cerulein injection was significantly higher than that in group I, II, and III rats. Significant differences in static lung compliance in group IV were found compared with groups I, II, and III. These results indicate that BAMs from rats with cerulein-induced pancreatitis were primed and had enhanced release of CINC following LPS exposure. Enhanced expression of CINC may modulate the pathogenesis of pancreatitis-associated lung injury complicated with sepsis.
 ...
PMID:Enhanced expression of cytokine-induced neutrophil chemoattractant (CINC) by bronchoalveolar macrophages in cerulein-induced pancreatitis rats. 900 32

We investigated the effects of the xanthine derivative propentofylline on lung injury in rats with cerulein-induced acute pancreatitis and endotoxemia. Pancreatitis was induced by four intramuscular injections of cerulein (50 micrograms/kg at 1-h intervals). Pancreatitis rats were injected intraperitoneally with 30 mg/kg lipopolysaccharide (LPS) 6 h following the first cerulein injection as a septic challenge. Propentofylline (50 mg/kg) was injected intravenously 15 min before the administration of LPS. Rats were divided randomly into five experimental groups: group I, normal rats; group II, pancreatitis; group III, LPS injection; group IV, pancreatitis and LPS injection; and group V, pancreatitis and LPS injection with propentofylline pretreatment. Serum amylase concentrations in groups II, IV, and V increased significantly 8 h after the first cerulein injection compared to those in groups I and III. Serum tumor necrosis factor (TNF)-alpha concentrations, cytokine-induced neutrophil chemoattractant (CINC) concentrations in serum or bronchoalveolar (BAL) fluid, lung myeloperoxidase (MPO) activity, and extent of pulmonary polymorphonuclear cell infiltration in group IV were significantly higher than those observed in group III. Pretreatment with propentofylline inhibited the rise in TNF-alpha levels (group V). However, propentofylline did not prevent the elevation of CINC levels in group V. In contrast, propentofylline reduced lung MPO and pulmonary PMN infiltration in group V. In addition, lung compliance was improved by pretreatment with propentofylline. These results suggest that propentofylline attenuates lung injury in an experimental model of pancreatitis complicated by endotoxemia but has differential effects on cytokine production.
 ...
PMID:Effects of propentofylline on tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant production in rats with cerulein-induced pancreatitis and endotoxemia. 909 57


1 2 3 4 5 6 7 8 Next >>