Water immersion stress induces heat shock protein 60 expression and protects against pancreatitis in rats.

Background & Aims: Heat shock proteins (Hsps), induced by cell stress, are known to protect against cellular injury. Recent studies have indicated that Hsp60 expression, induced by exposure to water immersion stress, protects against pancreatitis induced by administration of supramaximal doses of cerulein in rats. However, the mechanisms responsible for this protection are not known.

Heat shock protein 70 prevents secretagogue-induced cell injury in the pancreas by preventing intracellular trypsinogen activation.

Rodents given a supramaximally stimulating dose of cholecystokinin or its analogue cerulein develop acute pancreatitis with acinar cell injury, pancreatic inflammation, and intrapancreatic digestive enzyme (i.e., trypsinogen) activation.

Isolated extragenital bowenoid papulosis of the neck.

We report a case of extragenital bowenoid papulosis (BP) in a healthy immunocompetent 42-year-old man. The lesions occurred on the anterolateral aspects of the neck and were not associated with genital, oral, or periungual lesions. Lesional skin tested positive with the Digene hybrid capture system cocktail assay that identifies infection with a mixture of high to intermediate oncogenic human papillomavirus (HPV) types, including types 16, 18, 31, 33, 35, 45, 51, 52, and 56.

Repetitive short-term obstructions of the common bile-pancreatic duct induce severe acute pancreatitis in the opossum.

Gallstone pancreatitis is triggered by migrating stones that cause transient or continuous bile-pancreatic duct obstruction. One might hypothesize that the great clinical variability of acute pancreatitis is related to the inconsistent number and duration of a series of stone migrations. A new setting for the opossum model of acute pancreatitis was developed allowing reversible bile-pancreatic duct obstructions.

Secretagogue-induced digestive enzyme activation and cell injury in rat pancreatic acini.

The mechanisms responsible for intrapancreatic digestive enzyme activation as well as the relationship between that activation and cell injury during pancreatitis are not understood. We have employed an in vitro system in which freshly prepared pancreatic acini are exposed to a supramaximally stimulating concentration of the CCK analog caerulein to explore these issues. We find that in vitro trypsinogen activation depends on the continued presence of Ca2+ in the suspending medium and that it is half-maximal in the presence of 0.

The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury.

Background & Aims: Intercellular adhesion molecule 1 (ICAM-1) and neutrophils play important roles in many inflammatory processes, but their importance in both acute pancreatitis and pancreatitis-associated lung injury has not been defined.

Methods: To address this issue, mice that do not express ICAM-1 were used and depleted of neutrophils by administration of antineutrophil serum. Pancreatitis was induced by administering either supramaximal doses of the secretagogue cerulein or feeding a choline-deficient, ethionine-supplemented diet.

Pathophysiology of pancreatitis. Role of cytokines and other mediators of inflammation.

Acute pancreatitis is an inflammatory disease, which varies in severity from mild to severe. Factors determining the severity of pancreatitis are not known. It is generally believed that the earliest events in the evolution of acute pancreatitis lead to premature intra-acinar cell activation of digestive zymogens and that those enzymes, once activated cause acinar cell injury.

Ultrasound echogenicity in experimental venous thrombosis.

This study characterizes the echogenicity of experimentally induced venous thrombosis. Venous duplex imaging (Diasonics Spectra) was performed of the rat (n 12) and primate (n 3) inferior vena cava (IVC). Thrombosis was induced by IVC ligation at the level of the renal veins (rat, baboon) or balloon occlusion (baboon) of the IVC at the renal vein and iliac vein bifurcation level.

The effects of neutrophil depletion on a completely noninvasive model of acute pancreatitis-associated lung injury.

Conclusion: A completely noninvasive animal model of acute pancreatitis-associated lung injury was used to show that neutrophils, activated by pancreatitis, play a key role in mediating pancreatitis-associated lung injury.

Background: Significant pulmonary complications have been known to occur in over 50% of patients with severe acute pancreatitis. Recent studies using a variety of animal models of pancreatitis have suggested that neutrophil activation may play an important role in mediating lung injury.

Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis.

Background & Aims: Recent reports suggest that platelet-activating factor (PAF) plays a role in pancreatitis and pancreatitis-associated lung injury. In this study, the effects on these processes of termination of PAF action by recombinant PAF-acetylhydrolase (rPAF-AH) were investigated.

Methods: Rats were given rPAF-AH and then infused with a supramaximally stimulating dose of cerulein to induce mild pancreatitis.

Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats.

Supramaximal stimulation of the pancreas with the CCK analog caerulein causes acute edematous pancreatitis. In this model, active trypsin can be detected in the pancreas shortly after the start of supramaximal stimulation. Incubation of pancreatic acini in vitro with a supramaximally stimulating caerulein concentration also results in rapid activation of trypsinogen.

Induction of apoptosis in pancreatic acinar cells reduces the severity of acute pancreatitis.

1-Cyano-2-hydroxy-3-butene (CHB) has been reported to cause cell death in rat pancreatic acini. In this report, we describe the time-dependent effects of CHB on mouse acinar cell apoptosis and the effects of CHB-induced acinar cell apoptosis on the severity of secretagogue-induced acute pancreatitis in mice. CHB administration to mice resulted in a time-dependent increase in pancreatic apoptosis, which was maximal 12 hours after CHB administration.

Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury.

Substance P, acting via the neurokinin 1 receptor (NK1R), plays an important role in mediating a variety of inflammatory processes. However, its role in acute pancreatitis has not been previously described. We have found that, in normal mice, substance P levels in the pancreas and pancreatic acinar cell expression of NK1R are both increased during secretagogue-induced experimental pancreatitis.

Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury.

beta-Chemokines and their receptors mediate the trafficking and activation of a variety of leukocytes including the lymphocyte and macrophage. An array of no less than eight beta-chemokine receptors has been identified, four of which are capable of recognizing the chemokines MIP1alpha and RANTES. Genetic deletion of one of the MIP1alpha and RANTES receptors, CCR5, is associated with protection from infection with HIV-1 in humans, while deletion of the ligand MIP1alpha protects against Coxsackie virus-associated myocarditis.

A surgical wound infection due to Mycobacterium chelonae successfully treated with clarithromycin.

Background: Mycobacterium chelonae is an uncommon but recognized cause of chronic localized cutaneous infection at a site of penetrating trauma or a surgical wound.

Objective: The problem faced by physicians encountering an infection by M. chelonae is often response to therapy, which may be highly variable.

Cerulein-induced in vitro activation of trypsinogen in rat pancreatic acini is mediated by cathepsin B.

Background & Aims: One of the central, unresolved issues in the pathogenesis of acute pancreatitis is the uncertainty regarding the mechanisms responsible for the premature intrapancreatic activation of digestive enzyme zymogens. The aim of the current study was to develop and characterize an in vitro system that might mimic the events leading to trypsinogen activation within the pancreas during pancreatitis.

Methods: Activation of trypsinogen in response to stimulation with cerulein was quantitated in isolated rat pancreatic acini.

Clinical results of Greenfield filter use in patients with cancer.

The purpose of this report is to examine the outcomes for patients with an underlying diagnosis of malignancy who have had Greenfield vena caval filters placed for protection from pulmonary embolism, and to identify areas requiring further study. This was a retrospective review of data obtained from the Greenfield filter registry and the University of Michigan Tumor Registry for 166 patients treated at the University of Michigan Medical Center between January 1988 and June 1994. The 84 men and 82 women (mean age 57.

A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat pancreatic secretion.

The mechanisms by which short-term ethanol administration alters pancreatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. In our studies, anesthetized as well as conscious rats were given ethanol at a rate sufficient to cause the blood ethanol concentration to reach levels associated with clinical intoxication.

Protective effects of prostaglandin E1 on acute lung injury of caerulein-induced acute pancreatitis in rats.

Infusion of a supramaximally stimulating dose of the pancreatic secretagogue caerulein (10 micrograms.kg-1.h-1) for 4 h induces interstitial edematous acute pancreatitis in rats.

Effects of cycloheximide on pancreatic endonuclease activity, apoptosis, and severity of acute pancreatitis.

The factors that determine the severity of acute pancreatitis are unknown, but a close inverse correlation between that severity and the extent of acinar cell apoptosis that follows the triggering signal has been previously noted [A. M. Kaiser, A.

Edema and intrapancreatic trypsinogen activation precede glutathione depletion during caerulein pancreatitis.

Acute pancreatitis is characterized by hyperamylasemia, pancreatic edema, and the presence of activated digestive enzymes within the pancreas. The secretagogue-induced model of acute pancreatitis is also characterized by pancreatic acinar cell vacuolation, subcellular redistribution of lysosomal hydrolases, and a fall in pancreatic glutathione levels. We have performed time-dependence studies to determine the sequence with which these phenomena appear and to establish their cause-and-effect relationship.

Induction of apoptosis reduces the severity of caerulein-induced pancreatitis in mice.

The recent observation that the severity of pancreatitis is inversely related to the extent of apoptosis in five experimental models of the disease has suggested the possibility that apoptosis might protect against pancreatic injury in pancreatitis. This hypothesis was tested by inducing pancreatitis in mice during a phase of extensive apoptosis. Mice were fed a raw soya diet for five weeks to stimulate pancreatic growth and then switched to a regular chow diet for 27 hrs to permit involution of the hypertrophied gland.

Relationship between severity, necrosis, and apoptosis in five models of experimental acute pancreatitis.

In an effort to elucidate factors that determine the severity of an attack of acute pancreatitis, we have quantitated the extent of necrosis and of apoptosis in five different models of experimental acute pancreatitis. Severe pancreatitis was induced by obstructing the opossum common bile-pancreatic duct, by administering to mice 12 hourly injections of a supramaximally stimulating dose of caerulein, and by feeding young female mice a choline-deficient, ethionine-supplemented diet. In each of these models of severe pancreatitis, marked necrosis but very little apoptosis was found.

Biochemical and morphological changes that characterise recovery from necrotising biliary pancreatitis in the opossum.

The events that characterise recovery from severe biliary pancreatitis have not been defined. This study used a reversible model of necrotising pancreatitis, induced by obstructing the opossum common bile pancreatic duct (CBPD), to evaluate this phenomenon. The CBPD of opossums was obstructed with a balloon tipped catheter for five days and then decompressed by removal of the catheter.