Prevention and Amelioration of Rodent Ventilation-Induced Lung Injury with Either Prophylactic or Therapeutic feG Administration.

Purpose: Mechanical ventilation is a well-established therapy for patients with acute respiratory failure. However, up to 35% of mortality in acute respiratory distress syndrome may be attributed to ventilation-induced lung injury (VILI). We previously demonstrated the efficacy of the synthetic tripeptide feG for preventing and ameliorating acute pancreatitis-associated lung injury.

Prevention and amelioration of rodent endotoxin-induced lung injury with administration of a novel therapeutic tripeptide feG.

Background: The synthetic tripeptide feG is a novel pharmacological agent that decreases neutrophil recruitment, infiltration, and activation in various animal models of inflammatory disease. In human and rat cell culture models, feG requires pre-stimulation in order to decrease in vitro neutrophil chemotaxis. We aimed to investigate the effect of feG on neutrophil chemotaxis in a lipopolysaccharide-induced acute lung injury model without pre-stimulation.

Tripeptide feG prevents and ameliorates acute pancreatitis-associated acute lung injury in a rodent model.

Background: The synthetic tripeptide feG (D-Phe-D-Glu-Gly) is a novel pharmacologic agent that decreases neutrophil recruitment, infiltration, and activation in various animal models of inflammatory disease. We aimed to investigate the effect of feG as both a preventive treatment when administered before acute lung injury and as a therapeutic treatment administered following initiation of acute lung injury.

Methods: Lung injury was assessed following prophylactic or therapeutic intratracheal feG administration in a “two-hit” rodent model of acute pancreatitis plus intratracheal lipopolysaccharide.

Evaluation of lung injury and respiratory mechanics in a rat model of acute pancreatitis complicated with endotoxin.

Background: Acute lung injury (ALI) is a common complication of acute pancreatitis (AP) and contributes to the majority of AP-associated deaths, particularly in the setting of secondary infection. This 'two-hit' model mimics clinical cases where the presentation of AP is associated with mild lung injury that, following a secondary direct lung infection, can result in respiratory dysfunction and death. We therefore aimed to characterize lung injury in a clinically-relevant 'two-hit' rat model of caerulein-induced AP combined with intratracheal endotoxin.

Acute pancreatitis due to diabetes: the role of hyperglycaemia and insulin resistance.

Background: The co-existence of diabetes mellitus (DM) in patients with acute pancreatitis (AP) is linked to poor outcomes. Four large epidemiological studies have suggested an aetiological role for DM in AP. The exact nature of this role is poorly understood.

Pancreatic nociception--revisiting the physiology and pathophysiology.

Background: Pain management of many pancreatic diseases remains a major clinical concern. This problem reflects our poor understanding of pain signaling from the pancreas.

Objectives: This review provides an overview of our current knowledge, with emphasis on current pain management strategies and recent experimental findings.

Lung injury in acute pancreatitis: mechanisms underlying augmented secondary injury.

Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are common complications of acute pancreatitis (AP). ALI/ARDS contribute to the majority of AP-associated deaths, particularly in the setting of secondary infection. Following secondary pulmonary infection there can be an exacerbation of AP-associated lung injury, greater than the sum of the individual injuries alone.

L-Arginine-induced acute pancreatitis results in mild lung inflammation without altered respiratory mechanics.

Acute lung injury is a common complication of acute pancreatitis (AP) and contributes to the majority of AP-associated deaths. Although some aspects of AP-induced lung inflammation have been demonstrated, investigation of resultant changes in lung function is limited. The aim of this study was to characterize acute lung injury in L-arginine-induced AP.

Caerulein-induced acute pancreatitis results in mild lung inflammation and altered respiratory mechanics.

Acute lung injury is a common complication of acute pancreatitis (AP) and contributes to the majority of AP-associated deaths. Although some aspects of AP-induced lung inflammation have been demonstrated, investigation of resultant changes in lung function is limited. The aim of this study was to characterize lung injury in caerulein-induced AP.

Octreotide negates the benefit of galantide when used in the treatment of caerulein-induced acute pancreatitis in mice.

Background: We have previously shown that galantide, a non-specific galanin receptor antagonist, ameliorates acute pancreatitis (AP) induced in mice. Octreotide, a somatostatin analogue, has been used in the treatment of AP with inconsistent outcomes. This study set out to compare the efficacy of a combined treatment of galantide and octreotide with the efficacy of each agent individually in experimental AP.

Can by-products in country-made alcohols induce acute pancreatitis?

Objectives: We previously reported a high incidence of alcohol-related acute pancreatitis (AP) in Goa, India, where country-made alcoholic products are consumed in addition to the commercially available alcoholic products. We aimed to analyze the composition of these country-made alcoholic products consumed by a population with a high incidence of alcohol-related AP.

Methods: Three locally distilled alcoholic products (ethanol content, >20%) regularly consumed by patients developing AP, as determined by responses in a patient questionnaire, were selected.

The islet-acinar axis of the pancreas: more than just insulin.

Although the role of the islets in the regulation of acinar cell function seemed a mystery to investigators who observed their dispersion among pancreatic acini, over time an appreciation for this intricate and unique structural arrangement has developed. The last three decades have witnessed a steadily growing understanding of the interrelationship of the endocrine and the exocrine pancreas. The islet innervation and vascular anatomy have been more fully characterized and provide an appropriate background for our current understanding.

The efficacy of combining feG and galantide in mild caerulein-induced acute pancreatitis in mice.

We have previously shown that galantide ameliorates mild acute pancreatitis (AP), and the salivary tripeptide analogue, feG, ameliorates severe AP in mice. In this study, we compared the efficacy of combining galantide and feG with that of the individual agents in treating mild AP induced in mice with 7-hourly caerulein injections. Galantide was co-administered with each caerulein injection commencing with the first injection.

Alcohol-induced acute pancreatitis: the 'critical mass' concept.

The association of alcohol consumption and acute pancreatitis (AP) has been well documented. Extensive research in the field of alcohol-induced AP has allowed scientists to understand the different aspects by which ethanol may alter pancreatic cellular function. However, despite the recognition and understanding of these proposed mechanisms, the basic question that remains unanswered is that although alcohol is consumed the world over, why is it that only some people develop AP? Epidemiologic data indicates a higher frequency of alcohol-induced AP in geographical locations where surrogate/home-brewed alcoholic beverages are freely available.

Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse.

Objectives: Acute pancreatitis (AP) is characterized by pancreatic microcirculatory and secretory disturbances. As galanin can modulate pancreatic vascular perfusion, we sought to determine if galanin plays a role in AP.

Methods: Acute pancreatitis was induced in wild-type and galanin gene knockout mice by intraperitoneal injections of cerulein.

The combination of neurokinin-1 and galanin receptor antagonists ameliorates caerulein-induced acute pancreatitis in mice.

Both galanin and substance P have been separately implicated in the pathogenesis of acute pancreatitis. We compared the efficacy of the combination of the galanin antagonist galantide and the neurokinin-1 receptor antagonist L703,606 with that of either alone in the treatment of acute pancreatitis. Acute pancreatitis was induced in mice with 7-hourly caerulein injections.

Galanin potentiates supramaximal caerulein-stimulated pancreatic amylase secretion via its action on somatostatin secretion.

Galanin inhibits pancreatic amylase secretion from mouse lobules induced by physiological concentrations of caerulein via an insulin-dependent mechanism. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on pancreatic amylase secretion induced by supramaximal concentrations of caerulein. Amylase secretion from isolated murine pancreatic lobules was measured.

Galanin inhibits caerulein-stimulated pancreatic amylase secretion via cholinergic nerves and insulin.

Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in vitro. The effect of galanin on basal-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured.

Sleeve sphincter of Oddi (SO) manometry: a new method for characterizing the motility of the sphincter of Oddi.

Background/purpose: Perfused multilumen sphincter of Oddi (SO) manometry is accepted as the gold standard for diagnosis of SO dysfunction. However, this technique is associated with a relatively high incidence of post-procedure acute pancreatitis. In addition, triple-lumen manometry recordings may be difficult to interpret, as movement may produce artifacts.

Galanin in the regulation of pancreatic vascular perfusion.

Objectives: Acute pancreatitis is associated with compromised pancreatic microcirculation. Galanin is a vasoactive neuropeptide, but its role in the regulation of pancreatic vascular perfusion (PVP) is unclear.

Methods: Localization of galanin immunoreactivity was investigated by immunohistochemistry, and the effects of bolus doses of galanin or the antagonist galantide on blood pressure (BP) and PVP (by laser Doppler fluxmetry) were determined in anesthetized possums.

The tripeptide analog feG ameliorates severity of acute pancreatitis in a caerulein mouse model.

Acute pancreatitis (AP) is associated with significant morbidity and mortality; however, there is no specific treatment for this disease. A novel salivary tripeptide analog, feG, reduces inflammation in several different animal models of inflammation. The aims of this study were to determine whether feG reduced the severity of AP and modifies the expression of pancreatic ICAM-1 mRNA during AP in a mouse model.

Neurohormonal regulation of the sphincter of Oddi.

The control of sphincter of Oddi (SO) motor activity is complex and involves interactions between the SO smooth muscle with nerves, bioactive agents, and presumably interstitial cells of Cajal. Disturbances in SO motility are known to be related to painful clinical conditions, such as SO dysfunction and acute pancreatitis. Understanding normal SO motility and comparing this to disturbed SO motility patterns may identify mechanisms that could be targeted for future pharmacologic intervention.

Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis.

Objectives: Inducible nitric oxide synthase (iNOS) activity is increased in experimental acute pancreatitis. The aim of this study was to evaluate treatment with the selective iNOS inhibitors AR-C (AR-C102222AA) and L-NIL (L-N6-(1-iminoethyl)-lysine) in experimental acute pancreatitis.

Methods: Acute pancreatitis was induced in anesthetized Australian possums by topical administration of carbachol on the sphincter of Oddi.

Second-generation recombinant hemoglobin molecules do not stimulate sphincter of Oddi, gallbladder or duodenal motility in the Australian brush-tailed possum.

Background: Several studies have investigated the effects of hemoglobin-based oxygen carriers on gastrointestinal motility. Diaspirin cross-linked hemoglobin reduces sphincter of Oddi trans-sphincteric flow and increases duodenal motility in the Australian brush-tailed possum, effects attributed to nitric oxide (NO) scavenging. Recently, second-generation recombinant hemoglobin molecules with reduced NO scavenging ability have been developed.