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)

The present study was undertaken to investigate the involvement of PAF in acute pancreatitis induced by cerulein in rats. Cerulein (two doses of 20 micrograms/rat, the first s.c. and the second i.v., 1 h apart) induced a significant increase in vascular permeability in the pancreas, evaluated by the Evans blue (EB) extravasation method. Plasma amylase levels were also significantly increased in this group. The PAF antagonists, BN-52021 (5 mg/kg) and WEB-2170 (1 and 10 mg/kg), both significantly reduced the extravasation of EB in the pancrease induced by i.v. injection of PAF (1 microgram/kg). At these concentrations, BN-52021 was effective at inhibiting cerulein-induced pancreatitis (60-70% of inhibition) whereas WEB-2170 had no significant effect. Although the inhibition induced by BN-52021 suggests the involvement of PAF in cerulein-pancreatitis, the lack of effect of WEB-2170 reported here does not allow a definite conclusion. Further studies are needed to elucidate the differential effect of the PAF antagonists.
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PMID:Effect of PAF antagonists on cerulein-induced pancreatitis. 753 59

The effects of S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7, Oic8]bradykinin (BK)], a new, potent and long-acting BK B2 antagonist, were tested in some in vivo models of inflammation. In rats, S 16118 (0.1 and 1 mg/kg) given i.v. or s.c. delayed the edema formation induced by intraplantar carrageenan injections up to 4 hr after administration, confirming the involvement of kinins in this inflammatory reaction. In guinea pigs treated with atropine, vagal stimulation induced bronchial microvascular leakage. Aerosolization of S 16118 (5 x 10(-3) M for 20 sec), 4 min before vagus nerve stimulation, induced a 60% decrease in the Evans blue extravasation, demonstrating the modulatory role of BK in neurogenic inflammation. In rats, caerulein infusion (4 nmol/kg/hr) induced hypotension, massive pancreatic edema, hypovolemia due to plasma leakage and an increase in serum lipase and amylase activity. S 16118 (100 nmol/kg s.c.) prevented the hypotension, the pancreatic edema and the hypovolemia and induced a marked increase in the serum lipase and amylase activity. This confirms that BK, acting on BK B2 receptors, is involved in this model of pancreatitis. In rabbits, the injection of lipopolysaccharides (LPS; 600 micrograms/kg i.v.) induced hypotension, metabolic acidosis and leukopenia. S 16118 (1.73 mumol/kg i.v.) did not influence the effects of LPS injection. In mice, i.p. LPS (25 mg/kg) administration induced over 90% mortality in 96 hr. S 16118 (1 mg/kg x 4), given 30 min before LPS injection and 4, 8 and 24 hr after LPS injection, did not influence the mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the bradykinin B2 receptor antagonist S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) in different in vivo animal models of inflammation. 779 Oct 78

This study was designed to investigate the role of nitric oxide (NO) in the formation of pancreatic edema in caerulein-induced pancreatitis in rats. Pancreatitis was produced by two intraperitoneal injections of caerulein, and plasma amylase concentration, pancreatic edema index (pancreatic wet weight/body weight), and Evans blue extravasation (as a measure of vascular permeability) were evaluated 5 h after the first injection. Four doses (1, 2.5, 5, and 10 mg/kg) of NG-nitro-L-arginine (L-NNA), an NO synthase inhibitor, were subcutaneously administered at -0.5, 0.5, 1.5, 2.5, and 3.5 h after the first injection of caerulein. L-NNA significantly lowered the edema index, the wet/dry weight ratio of the pancreas, and Evans blue extravasation in the rats with pancreatitis. The maximal effect was obtained by L-NNA at a dose of 2.5 mg/kg; this inhibited the increase in pancreatic edema formation from the control value by 60%-70%. Intraperitoneal injections (20 mg/kg, five times) of L-arginine, a substrate for NO production, partly reversed the L-NNA-induced inhibition of pancreatic edema formation, but D-arginine, an enantiomer of L-arginine, did not show any effect. Plasma amylase concentrations were not significantly affected by any dose of L-NNA, nor were they affected by L- or D-arginine. These findings strongly suggest that endogenous NO plays an important role in the formation of pancreatic edema in caerulein-induced pancreatitis in rats, probably by increasing vascular permeability and protein extravasation.
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PMID:Nitric oxide modulates pancreatic edema formation in rat caerulein-induced pancreatitis. 857 37

This study aimed to determine whether laparoscopic splenectomy is more advantageous than open splenectomy in pediatric patients. Data from 61 patients treated between June 1983 and September 1994 were reviewed. Length of hospitalization, hospital costs, operating time, and postoperative complications were evaluated. Forty-seven patients had open splenectomy. Nineteen of these underwent concomitant procedures. Fourteen patients had laparoscopic splenectomy, and four had concomitant cholecystectomy. The data show a trend toward a 1-day reduction in hospital stay associated with laparoscopic splenectomy (P < .02). Operating time was 83% longer for the laparoscopic approach (P < .001), and operating costs were almost $3,000 more (P < .001) than for open splenectomy. The total hospital cost also was greater for laparoscopic procedures (P < .1), primarily reflective of a more than $3,000 difference for splenectomy alone (P < .02). Two of the fourteen laparoscopic patients (14%) had complications. One patient with Evan's syndrome had pneumonia that required antibiotics. Another patient required conversion to an open procedure because of poorly controlled hemorrhage from a short gastric vessel. Twelve of the open splenectomy patients (25%) had complications: atelectasis (3), fever (4), wound infection (2), pneumonia (1), laryngospasm (1), and pancreatitis (1). The authors conclude that laparoscopic splenectomy is a safe but currently more expensive alternative to open splenectomy, primarily because of the use of disposable instruments. Benefits include a shorter hospital stay, no greater risk of postoperative complications, and subjective improvement in the cosmetic result. Disadvantages include increased operating time and cost. Evaluation of larger series will be needed to determine the significance of the difference in complication rates between the two procedures.
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PMID:A comparison of laparoscopic and traditional open splenectomy in childhood. 863 60

Acute pancreatitis is associated with the development of pulmonary dysfunction in a number of patients. The aim of this study was to determine whether acute lung injury was a feature of the microembolic model of pancreatitis in rats and to assess the therapeutic effect of lexipafant (BB-882), a potent platelet-activating factor antagonist, on the lung injury. Acute pancreatitis was induced by microembolisation of the pancreas with 20-microns polystyrene microspheres. After 12 h tissue capillary permeability was assessed by an Evans blue dye (EBD) extravasation technique and compared with that in control animals. A further group of animals received an intraperitoneal injection of BB-882 (5 mg/kg) 30 min after the induction of pancreatitis. There was a significantly increased tissue content of EBD in the pancreas and lungs of the group of animals with acute pancreatitis (p < 0.05). BB-882 ameliorated the pulmonary changes when administered after the induction of pancreatitis, as demonstrated by a significant reduction in the EBD content of the lungs (p < 0.01). Increased pulmonary vascular permeability is an early feature of the microembolic model of acute pancreatitis and these changes appear to be modified by the administration of BB-882, providing further evidence for the potential role of platelet-activating factor antagonists in the treatment of acute pancreatitis and its complications.
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PMID:Lung injury in the microembolic model of acute pancreatitis and amelioration by lexipafant (BB-882), a platelet-activating factor antagonist. 882 81

Recent studies provide significant evidence that cholecystokinin (CCK) is involved in the induction and development of acute pancreatitis in experimental animals. However, the results obtained with specific CCK-A (peripheral) receptor antagonists are still controversial. The present studies were undertaken to evaluate the involvement of endogenous CCK and the CCK-A receptors in the development of severe acute pancreatitis induced in Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have a selective defect in the CCK-A receptor. Three models of severe acute pancreatitis were induced by retrograde intraductal infusion of 4% sodium taurocholate, by the closed duodenal loop, or by a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine in OLETF rats and control Long-Evans Tokushima Otsuka (LETO) rats. Plasma CCK levels rose up to 4- to 14-fold over the preloading values after the onset of acute pancreatitis in all three models in both groups of rats. However, histologic alterations as well as the magnitudes of increase in serum amylase and lipase activity and the pancreatic wet weight were significantly less in the OLETF rats than those in the LETO rats. In addition, 72 h after the onset of arginine pancreatitis, massive destruction of pancreatic parenchyma with a significant reduction in serum amylase and lipase activities and pancreatic wet weight was observed in the LETO rats, whereas these changes were not seen in OLETF rats. These results suggest that endogenous CCK and CCK-A receptors play a role in the development of severe acute pancreatitis in rats.
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PMID:Role of endogenous cholecystokinin and cholecystokinin-A receptors in the development of acute pancreatitis in rats. 905 82

Lung injury develop in up to 50-70 percent of patients with acute pancreatitis. Cerulein in physiological doses reduces the rate mortality of pancreatitis by decreasing the enzyme content of the pancreas. In order to assess the effect of acute reduction of pancreatic enzyme content on the pancreatitis pulmonary injury, pancreatitis was induced in Wistar rats by intraductal injection of 5 per cent sodium taurocholate: group I, with pancreatitis; group II, pancreatitis after decreasing pancreatic enzyme content; group III, control group. Dye Evans blue was used to evaluate the lung injury. The pancreatitis pulmonary injury was smaller in group II than group I (P < 0.05) but it was similar to control group (group III). In conclusion, it is speculated that the reduction of the pancreatic enzyme content reduces the pancreatitis pulmonary injury by decreasing the quantity of pancreatic enzymes reaching the systemic circulation.
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PMID:[Protective effect of reduction of pancreatic enzyme content on the pulmonary disease induced by acute pancreatitis]. 920 26

We examined the role of the cholecystokinin-A (CCK-A) receptor in acute inflammatory and regenerative stages of experimental pancreatitis using a rat model lacking the CCK-A receptor [Otsuka Long-Evans Tokushima Fatty (OLETF) rats]. OLETF and control [Long-Evans Tokushima Otsuka (LETO)] rats were prepared with an internal bile fistula and with obstruction of pancreatic flow and were sacrificed 1-14 days later. Histological examination was performed, and changes in pancreatic wet weight, protein concentration, CCK-A and -B receptor mRNA levels, tyrosine kinase activities, and plasma amylase and CCK levels were determined. The plasma amylase level showed a transient increase on day 1, the CCK level remained at high levels throughout, and tyrosine kinase activity was increased significantly on day 3 but declined thereafter. These parameters were comparable for both strains during the acute inflammatory stage. However, no regenerative findings were observed by histological examination and the protein concentration in the pancreas was significantly lower in OLETF rats on days 7-14, during which time regeneration was completed in LETO rats. These observations indicate that the absence of the CCK-A receptor did not modify the acute phase of pancreatitis but significantly retarded regeneration of the pancreatic tissue.
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PMID:Role of cholecystokinin-A (CCK-A) receptor in pancreatic regeneration after pancreatic duct occlusion: a study in rats lacking CCK-A receptor gene expression. 951 Jan 32

Pancreatic encephalopathy is a severe complication of acute pancreatitis. Proinflammatory cytokines may play a role in the development of multi-organ failure during pancreatitis. In the present study, we measured the changes in the blood-brain barrier (BBB) permeability concomitantly with the determination of serum tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in rats before, as well as 6, 24 and 48 h after the beginning of intraductal taurocholic acid-induced acute pancreatitis. Cytokine concentrations were measured in bioassays with specific cell lines (WEHI-164 for TNF and B-9 for IL-6), while the BBB permeability was determined for a small (sodium fluorescein, molecular weight (MW) 376 Da), and a large (Evans' blue-albumin, MW 67000 Da) tracer by spectrophotometry in the parietal cortex, hippocampus, striatum, cerebellum and medulla of rats. The serum TNF level was significantly (P < 0.05) increased 6 and 24 h after the induction of pancreatitis, while the IL-6 level increased after 24 and 48 h. A significant (P < 0.05) increase in BBB permeability for both tracers developed at 6 and 24 h in different brain regions of animals with acute pancreatitis. We conclude that cytokines, such as TNF and IL-6, may contribute to the vasogenic brain edema formation during acute pancreatitis.
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PMID:Experimental acute pancreatitis results in increased blood-brain barrier permeability in the rat: a potential role for tumor necrosis factor and interleukin 6. 953 Sep 27

Pancreatic oedema occurs early in the development of acute pancreatitis, and the overall extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is released from sensory nerves, binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process termed neurogenic inflammation. We sought to determine the importance of neurogenic mechanisms in acute pancreatitis. Pancreatic plasma extravasation was measured using the intravascular tracers Evans blue and Monastral blue after administration of specific NK1-R agonists/antagonists in rats and NK1-R(+/+)/(-/-) mice. The effects of NK1-R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein-induced pancreatitis were characterized. In rats, both SP and the NK1-R selective agonist [Sar(9) Met(O(2))(11)]SP stimulated pancreatic plasma extravasation, and this response was blocked by the NK1-R antagonist CP 96,345. Selective agonists of the NK-2 or NK-3 receptors had no effect. In rats, cerulein stimulated pancreatic plasma extravasation and serum amylase. These responses were blocked by the NK1-R antagonist CP 96,345. In wildtype mice, SP induced plasma extravasation while SP had no effect in NK1-R knockout mice. In NK1-R knockout mice, the effects of cerulein on pancreatic plasma extravasation and hyperamylasemia were reduced by 60%, and pancreatic MPO by 75%, as compared to wildtype animals. Neurogenic mechanisms of inflammation are important in the development of inflammatory oedema in acute interstitial pancreatitis.
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PMID:Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice. 1082 77


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