p8 is a transcription cofactor whose expression is strongly and rapidly activated in pancreatic acinar cells during the acute phase of pancreatitis. A p8-deficient mouse strain was generated as a tool to investigate its function. Upon induction of acute pancreatitis, myeloperoxidase activity in pancreas and serum concentrations of amylase and lipase were much higher and pancreatic lesions more severe in p8-deficient mice than in wild-type, indicating that p8 expression decreased pancreatic sensitivity to pancreatitis induction. The protective mechanism might involve the pancreatitisassociated protein (PAP I), whose strong induction during pancreatitis is p8-dependent, because administration of anti-PAP I antibodies to rats increased pancreatic inflammation during pancreatitis. In addition, 100 ng/ml PAP I in the culture medium of macrophages prevented their activation by tumor necrosis factor ␣, strongly suggesting that PAP I was an anti-inflammatory factor. Finally, PAP I was able to inhibit NFB activation by tumor necrosis factor ␣, in macrophages and in the AR42J pancreatic acinar cell line. In conclusion, p8 improves pancreatic resistance to inducers of acute pancreatitis by a mechanism implicating the expression of the anti-inflammatory protein PAP I.
Intracellular Ca2؉ -changes not only participate in important signaling pathways but have also been implicated in a number of disease states including acute pancreatitis. To investigate the underlying mechanisms in an experimental model mimicking human gallstone-induced pancreatitis, we ligated the pancreatic duct of Sprague-Dawley rats and NMRI mice for up to 6 h and studied intrapancreatic changes including the dynamics of [ influx in response to secretagogue stimulation. Serum pancreatic enzyme elevation as well as trypsinogen activation was significantly reduced by pretreatment of animals with the calcium chelator BAPTA-AM. These experiments suggest that pancreatic duct obstruction rapidly changes the physiological response of the exocrine pancreas to a Ca 2؉ -signaling pattern that has been associated with premature digestive enzyme activation and the onset of pancreatitis, both of which can be prevented by administration of an intracellular calcium chelator.Alterations in intracellular calcium signaling have previously been reported from an experimental animal model of acute pancreatitis that employs supramaximal secretagogue stimulation for the disease induction (1). Moreover, the spatial and temporal distribution of intracellular calcium signals in response to either physiological or pathological stimuli has been found to be directly related to premature digestive enzyme activation in the pancreas and to acinar cell injury (2-5). Intracellular activation of trypsinogen on the other hand can be completely prevented with agents that interfere with either the uptake of calcium, the maintenance of a calcium gradient across the plasma membrane, or the rapid release of calcium from apical intracellular stores (4, 6). All of these studies indicate clearly that the spatial and temporal distribution of intracellular calcium signals plays a critical role in the early cellular events that precede the onset of pancreatitis. The mechanism, however, that was used to induce acinar cell injury in these studies or in response to which intracellular calcium changes were characterized, supramaximal secretagogue stimulation, is not necessarily an event that is generally involved in the pathogenesis of clinical pancreatitis.In many parts of the world the most common etiological factor associated with acute pancreatitis is gallstone disease. Experimental (7) as well as clinical studies (8, 9) suggest that the onset of gallstone-induced pancreatitis requires migration of the offending stone through the biliary tract and its impaction at the duodenal papilla. Here, at the junction of the common bile duct and the pancreatic duct, the stone can impair the flow of pancreatic secretion or lead to a complete blockage of the pancreatic duct. It is now generally accepted that this impairment of pancreatic secretion (7, 10, 11), rather than a potential reflux of bile into the pancreas (13), represents the critical pathophysiological event for the development gallstoneinduced pancreatitis. To investigate whether this clinically relevant...
The incidence of acute pancreatitis varies considerably between regions and is estimated at 5-80 per 100,000 population. The mortality rate of acute edematous-interstitial pancreatitis is below 1%, whereas 10-24% of patients with severe acute pancreatitis die. The early prognostic factors that can be used to determine whether the clinical course is likely to be severe are three or more signs of organ failure according to the Ranson or Imrie scores, the presence of nonpancreatic complications, and the detection of pancreatic necrosis by imaging techniques. Elevated C-reactive protein levels above 130 mg/l can also predict a severe course of acute pancreatitis with high sensitivity. Although no causal treatment exists, replacing the dramatic fluid loss that takes place in the early disease phase is critical and determines the patient's prognosis. Adequate pain relief with opiates is another therapeutic priority. In patients with pancreatic necrosis, the high mortality rate between the third and fourth week after the initial episode is determined largely by the development of pancreatic infection, and can therefore be reduced by early antibiotic treatment. Early enteral nutrition for the treatment of acute pancreatitis has been shown to be superior and much more cost-effective than parenteral nutrition. Infected pancreatic necrosis or pancreatic abscess are two of the few remaining indications for open surgery in acute pancreatitis. Even when indicated, surgery is frequently delayed or even replaced by minimally invasive surgical techniques.
Thoracic epidural analgesia attenuated systemic response and improved survival in severe acute pancreatitis. These effects might be explained by improved mucosal perfusion.
Cystic lesions located in the gastric wall are a rare finding in endosonography of the gastrointestinal tract. Compared to all forms of benign and malignant tumours of the stomach, gastric duplication cysts are an uncommon anomaly--especially in adults. We report on a 59-year-old woman suffering from intermittent abdominal pain, weight loss and nausea. A gastric duplication cyst was identified by endoscopic ultrasound (EUS), but malignancy was excluded by EUS and fine-needle aspiration histology. Because of continuously increasing abdominal complaints, surgery was performed with partial resection of the gastric corpus and splenectomy. Gross anatomy and histology showed a gastric cyst measuring 150 mm in maximum diameter with no evidence of malignancy or inflammation. Following surgery, the patient's condition recovered fully.
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