Pathogenesis and Pathophysiology of Acute Pancreatitis

Steer, Michael L.; Perides, George

doi:10.1007/978-3-540-28656-1_16

Cited by 26 publications

(41 citation statements)

References 60 publications

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“…Various causes, including gallstones, alcohol, trauma, infections, and genetic alterations, have been implicated in the causation of this disease (1,23). Although our understanding of the cell biology of the exocrine pancreas and epidemiology of pancreatitis has increased greatly in recent years, our knowledge of its pathophysiology and the ability to prevent or treat pancreatitis remain limited (23).…”

mentioning

confidence: 99%

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

Dawra

Sharif

Phillips

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

163

131

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Dawra R, Sharif R, Phillips P, Dudeja V, Dhaulakhandi D, Saluja AK. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol 292: G1009 -G1018, 2007. First published December 14, 2006; doi:10.1152/ajpgi.00167.2006.-The pathogenesis of acute pancreatitis is not fully understood. Experimental animal models that mimic human disease are essential to better understand the pathophysiology of the disease and to evaluate potential therapeutic agents. Given that the mouse genome is known completely and that a large number of strains with various genetic deletions are available, it is advantageous to have multiple reliable mouse models of acute pancreatitis. Presently, there is only one predominant model of acute pancreatitis in mice, in which hyperstimulatory doses of cholecystokinin or its analog caerulein are administered. Therefore, the aim of this study was to develop another mouse model of acute pancreatitis. In this study, C57BL/6 mice were injected intraperitoneally with L-arginine in two doses of 4 g/kg each, 1 h apart. Serum amylase, myeloperoxidase, and histopathology were examined at varying time points after injection to assess injury to the pancreas and lung. We found that injection of L-arginine was followed by significant increases in plasma amylase and pancreatic myeloperoxidase accompanied by marked histopathological changes. The injury to the pancreas was slow to develop and peaked at 72 h. Subsequent to peak injury, the damaged areas contained collagen fibers as assessed by increased Sirius red staining. In contrast, D-arginine or other amino acids did not cause injury to the pancreas. In addition, acute inflammation in the pancreas was associated with lung injury. Our results indicate that administration of L-arginine to mice results in severe acute pancreatitis. This model should help in elucidating the pathophysiology of pancreatitis.pancreas; lung injury; fibrosis ACUTE PANCREATITIS IS AN INFLAMMATORY disease of the pancreas resulting in significant morbidity and mortality (13). Various causes, including gallstones, alcohol, trauma, infections, and genetic alterations, have been implicated in the causation of this disease (1, 23). Although our understanding of the cell biology of the exocrine pancreas and epidemiology of pancreatitis has increased greatly in recent years, our knowledge of its pathophysiology and the ability to prevent or treat pancreatitis remain limited (23). This can partially be attributed to the paucity of clinical material from the early stages of the disease available for research. To overcome this and to study the effect of new therapeutic agents, different experimental animal models of pancreatitis have been developed. Our present limited understanding about the events associated with the development of the disease is based on the use of these experimental models (21). Among the animals used for developing experimental models, the mouse is ideal because of the availability of several genetic man...

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mentioning

confidence: 99%

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

Dawra

Sharif

Phillips

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

163

131

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“…Although the mechanisms underlying these processes remain incompletely understood, the morphological and functional changes include sequestration of inflammatory cells within the lung (2,7,37), injury to the pulmonary microvascular surface (19), and extravasation of otherwise intravascular fluid across the microvascular endothelial barrier into the bronchoalveolar space (21). Acute lung injury and ARDS, along with other elements of SIRS, are frequently noted in patients with severe acute pancreatitis (30). Roughly 40% of patients who die during the early stages of severe pancreatitis succumb from lung injury and respiratory failure.…”

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confidence: 99%

In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury

Frossard

Saluja²,

Mach

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Severe pancreatitis is frequently associated with acute lung injury (ALI) and the respiratory distress syndrome. The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mediating the ALI associated with secretagogue-induced experimental pancreatitis was evaluated with GM-CSF knockout mice (GM-CSF −/−). Pancreatitis was induced by hourly (12×) intraperitoneal injection of a supramaximally stimulating dose of the cholecystokinin analog caerulein. The resulting pancreatitis was similar in GM-CSF-sufficient (GM-CSF +/+) control animals and GM-CSF −/− mice. Lung injury, quantitated by measuring lung myeloperoxidase activity (an indicator of neutrophil sequestration), alveolar-capillary permeability, and alveolar membrane thickness was less severe in GM-CSF −/− than in GM-CSF +/+ mice. In GM-CSF +/+ mice, pancreas, lung and serum GM-CSF levels increase during pancreatitis. Lung levels of macrophage inflammatory protein (MIP)-2 are also increased during pancreatitis, but, in this case, the rise is less profound in GM-CSF −/− mice than in GM-CSF +/+ controls. Administration of anti-MIP-2 antibodies was found to reduce the severity of pancreatitis-associated ALI. Our findings indicate that GM-CSF plays a critical role in coupling pancreatitis to ALI and suggest that GM-CSF may act indirectly by regulating the release of other proinflammatory factors including MIP-2.

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“…Although the pathogenesis of acute pancreatitis is not fully understood, the key event is considered to be the inappropriate release and intrapancreatic activation of pancreatic proenzymes (1). Cholecystokinin (CCK) is known to stimulate secretion of the pancreatic digestive enzymes via the CCKA receptor (2).…”

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confidence: 99%

Effect of T-0632, a CholecystokininA Receptor Antagonist, on Experimental Acute Pancreatitis.

Taniguchi¹,

Yomota²,

Kume³

et al. 1997

Jpn.J.Pharmacol

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Pathogenesis and Pathophysiology of Acute Pancreatitis

Cited by 26 publications

References 60 publications

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury

Effect of T-0632, a CholecystokininA Receptor Antagonist, on Experimental Acute Pancreatitis.

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