Causes and Mechanisms in Acute Pancreatitis

Waldthaler, Alexander; Schütte, Kerstin; Malfertheiner, Peter

doi:10.1159/000319416

Cited by 34 publications

(21 citation statements)

References 107 publications

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“…However, severe acute pancreatitis can be life-threatening and requires management in intensive care units. Although extensive research and clinical efforts have been made in the management of acute pancreatitis in the past few decades [7], to date no effective cure is available [3,8]; the mortality resulted from severe acute pancreatitis remains high [9]. It is therefore urgently needed to explore novel therapeutic strategies to improve the outcome of patients with severe pancreatitis.…”

Section: Introductionmentioning

confidence: 99%

Potential of sivelestat in protection against severe acute pancreatitis-associated lung injury in rats

Wang

Tang

Chen

et al. 2012

Experimental Lung Research

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The incidence of acute pancreatitis has been rising worldwide in the past few decades. Despite extensive research efforts, the population-based mortality from acute pancreatitis remains high. Since dysfunction of multiple vital organs, most importantly the lungs, is the major cause of early death in acute pancreatitis patients, developing effective strategies to manage lung injury has become one of the focuses of recent research efforts aiming at improving the outcome of patients with acute pancreatitis. In this study, we attempted to create a rat model of acute pancreatitis through intraductal infusion of taurocholate and to evaluate the potential of sivelestat, a synthetic neutrophil elastase inhibitor, in protection against acute pancreatitis-associated lung injury using this rat model. The results demonstrated that: (1) 5% sodium taurocholate successfully induced histopathologic and biochemical abnormalities in the circulation, lung and pancreas characteristic of human acute pancreatitis, including an increase in amylase concentration and a decrease in partial arterial oxygen pressure (PaO2) in the blood, increases in activities of myeloperoxidase (MPO) (a lung injury marker) and neutrophil elastase (a quantitative indicator of neutrophil infiltration), and levels of malondialdehyde (an indicator of lipid peroxidation) and tumor necrosis factor-alpha (a major inflammatory mediator) in the lung; (2) intravenous administration of sivelestat effectively attenuated the taurocholate-induced abnormalities in all parameters analyzed except for serum amylase concentration. Our findings have validated the taurocholate model of acute pancreatitis and demonstrated great therapeutic potential for sivelestat in managing acute pancreatitis-associated lung injury.

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Section: Introductionmentioning

confidence: 99%

Potential of sivelestat in protection against severe acute pancreatitis-associated lung injury in rats

Wang

Tang

Chen

et al. 2012

Experimental Lung Research

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“…Several models of acute pancreatitis have shown intra-acinar activation of the zymogen trypsinogen to trypsin as playing an important role in disease pathogenesis (2)(3)(4). This process is thought to be important in pancreatitis because trypsin is a "master activator" of the digestive enzyme cascade.…”

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confidence: 99%

ADP-ribosylation Factor 1 Protein Regulates Trypsinogen Activation via Organellar Trafficking of Procathepsin B Protein and Autophagic Maturation in Acute Pancreatitis

Orlichenko

Stolz

Noel

et al. 2012

Journal of Biological Chemistry

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Background: Autophagy and cathepsin B-mediated trypsin generation may be deleterious in acute pancreatitis. The role of ARF1 in the process is unknown. Results: BFA-mediated ARF1 inhibition prevents caerulein-induced processing of procathepsin B and perturbs autophagic maturation. Conclusion: ARF1-dependent trafficking of procathepsin B and autophagic maturation result in trypsinogen activation. Significance: ARF1 plays a significant role in acute pancreatitis.

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“…For instance hypercalcaemia, extreme levels of serum triglycerides, cystic fibrosis and many others have been described as risk factors for acute pancreatitis 36 . However, the first two co-morbidities explain less than 1 per cent of all cases of acute pancreatitis, and cystic fibrosis should not influence the observed associations in this study population in view of the mean age.…”

Section: Discussionmentioning

confidence: 99%