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The association between chronic pancreatitis (CP) and primary sclerosing cholangitis (PSC) has been reported previously. The aims of the present study were to evaluate the presence of early pancreatic abnormalities and duct changes, using MRCP/MRI in PSC and to evaluate possible risk factors for these changes and their clinical importance.One hundred and three patients with PSC were identified among all MRI liver/pancreas referrals in 2001-2005. MRCP was used to grade pancreatic duct changes in three groups: grade 0 (normal), grade 1 (mild) and grade 2 (severe). For detection of early MRI signs of CP, the pancreas-spleen signal intensity ratio (SIR), the arterial and early venous phase ratio (A/PV ratio) and the age-related size of the pancreas were evaluated.Pancreatic duct changes were found in 24% of the PSC patients. The pancreatic duct changes were associated with extrahepatic biliary involvement and long duration of PSC but not associated with pancreas-spleen SIR, A/PV ratio, pancreas size, previous post-ERCP or acute pancreatitis. Severe pancreatic duct changes were significantly associated to abdominal pain. Clinically significant CP was seen in one PSC patient (1%).Pancreatic duct changes are associated with extrahepatic bile duct strictures and not with the early MRI signs of CP. Therefore, pancreatic duct changes seem to be part of the spectrum of PSC and should not be defined as CP. Pancreatic duct changes are of limited clinical importance but may contribute to abdominal pain in PSC.

Obesity is associated with increased severity in patients with acute pancreatitis (AP). The underlying mechanisms are unknown. Genetically obese rats exhibit decreased survival rate in experimental AP, but the clinical relevance of this model of obesity may be questioned. It is proposed that development of organ failure in AP occurs in two stages: initial priming of leucocytes followed by a second inflammatory attack. The aim was to evaluate the impact of diet-induced obesity on outcome in a 'two-hit' model of AP.Lipopolysaccharide (LPS) was injected i.p. 3 h after retrograde bile duct infusion of sodium taurocholate in rats. Three experiments were done: 1) an LPS dose-response experiment, 2) chronic high-fat feeding (HF) for 16 weeks, and 3) acute HF for 10 days. Control rats received normal chow. Obesity, morphology and survival rate were assessed.LPS dose-dependently decreased survival rate and increased morphological severity. HF increased weight, intra-abdominal and liver fat. Only acute HF induced hyperlipidaemia. In AP, acute obese rats exhibited less pancreatic inflammation, but total histological severity between groups was not different. In the chronic experiment only obese animals succumbed before 24 h of pancreatitis, but 72-h survival rate was not statistically different in either high-fat experiment.An addition of LPS to AP decreases survival rate and intensifies the peri-pancreatic processes. Despite significant obesity, neither hyperlipidaemia nor increased intra-abdominal or hepatic fat influenced local pancreatic injury or survival negatively. The amount of fat per se seems not to be responsible for the deleterious influence of obesity on acute pancreatitis.

Studies in patients with acute pancreatitis have shown a correlation between obesity and serious complications or a fatal outcome. However, the mechanisms by which obesity aggravates acute pancreatitis are not known. In the present study we used the sodium taurocholate model of pancreatitis to examine the effect of obesity on severity and outcome in acute experimental pancreatitis (AEP).AEP was induced at two degrees of severity by retrograde infusion of sodium taurocholate (0.2 ml x 3% or 0.4 ml x 3.5%) into the pancreatic duct of rats with obesity induced by high-fat diet, genetically obese (GO) rats or lean control rats. Surviving animals were sacrificed 72 h after induction of pancreatitis.In the low-dose experiment, there were no significant differences in pancreatic histology or survival rate between the groups. In the high-dose experiment, the GO rats had a significantly lower 72-h survival rate than the high-fat obese (HFO) or lean control (LC) groups (GO 25% versus HFO 73%, P0.05; GO 25% versus LC 100%, P0.001). Survival rates in the high-dose experiment correlated strongly with basal liver fat content (R2 = 0.86). Pancreatic histology showed significantly more fat necrosis and a higher total pathological mean score in the HFO rats than in the LC animals (both P0.05).Obesity had a negative influence on the outcome of necrotizing pancreatitis that was related to the magnitude of the pancreatic insult. The sodium taurocholate model in obese rats would be useful for future mechanistic studies of the effect of obesity on pancreatitis.

The development of front-line endoscopic technology has introduced new opportunities during endoscopic retrograde cholangiopancreatography (ERCP) to single-handedly allow direct inspection of detailed structures of the biliary and even the pancreatic duct. This paper presents a new flexible technology delivered with an outer diameter of 0.9 mm giving an image transmission of 6000 pixels. We report on a case where direct inspection of an alleged duct defect, of potential pathogenetic significance, was considered essential in order to substantiate the subsequent clinical management.

Luminal nutrients and growth factors regulate postresectional intestinal growth. The interplay between glutamine and regulatory gastrointestinal peptides is not known.The effects of intestinal resection on tissue and plasma concentrations of peptides were studied in 60 Sprague-Dawley rats divided into resected, transected, or unoperated groups. Subgroups were fed either a glutamine-free or a glutamine-supplemented diet for 7 days. Epidermal growth factor, transforming growth factor-alpha, insulin-like growth factors (IGF) I and II, peptide YY (PYY), and enteroglucagon were analyzed in intestinal mucosa and in portal plasma by radioimmunoassay.No glutamine-specific effects were seen. The mucosal content of IGF-II (P0.01) and the portal levels of enteroglucagon and PYY (P0.05-0.01) increased after intestinal resection.The increase in PYY and enteroglucagon in portal blood supports a hormonal role in the postresectional adaptation. The increase in IGF II in the ileal mucosa, without changes in plasma, implies autocrine or paracrine growth stimulation at this stage after resection.

Islet amyloid polypeptide (IAPP), also called amylin, is a hormonal peptide produced by the islet beta-cells of the pancreas. Because the peptide is co-stored and co-released with insulin, attention has been focused on IAPP's ability to interfere with glucose metabolism. However, IAPP also has other effects, such as a reduction of food intake.In this study we investigated the dose-response effect of acute systemic administration of rat and human IAPP on food intake, and the cumulative effect of chronically increased circulating IAPP concentrations on food intake and body weight in the rat.All doses of rat IAPP investigated acutely inhibited food intake. The lowest infusion rate of 8 pmol/kg/min caused an 28% inhibition of the food intake at 2 h (p0.05). No effect of human IAPP was observed. Chronic administration of rat IAPP via an osmotic minipump during a 6-day period caused prolonged inhibitory effects on food intake and reduced body weight. During the first 3 days of infusion the food intake of the IAPP group was only 44% of the food intake of the control group (p0.001). The body weight of the IAPP group had fallen 18.6 +/- 2.7 g by day 3, in contrast to a small increase in the control group (4.0 +/- 3.1 g; p0.001). The reduction in food intake was sustained throughout the last 3 days of study (IAPP, 16.7 +/- 1.1 g/day; control, 20.6 +/- 1.5; p0.05). Similarly, the body weight still differed at the end of day 6 and, compared with day 0, was -8.7 +/- 3.7 g for the IAPP group and +10.9 +/- 4.8 for the control group (p0.01).These findings show that chronic increase of circulating IAPP levels can cause a marked reduction in both food intake and body weight and, together with the reduced food intake seen after acute administration of the peptide, indicates the possibility of IAPP functioning as a satiety factor.

The current study used islet amyloid polypeptide (IAPP) knockout mice (KO mice) to investigate the physiological role of IAPP in the regulation of food intake (FI).FI and body weight were measured in KO and wild-type (WT) mice for 27 weeks. In an additional short-term experiment, IAPP (25 pmol·kg(-1)min(-1)) was infused subcutaneously for 3 days in KO and WT mice, and FI, meal pattern, and body weight were analyzed.In the long-term experiment, no significant differences in body weight were seen between WT and KO mice at any point. FI, meal number, and meal size did not differ significantly between the groups in any of the five selected weeks that were studied. In the short-term experiment, FI decreased significantly during IAPP infusion in both WT and KO groups. FI was significantly lower in the KO mice compared with WT on days 1 and 2 (p0.05 and p0.01, respectively).The data showing no differences in FI and body weight were seen between KO and WT mice, indicating that FI can be controlled in the absence of IAPP. The more marked anorectic effect seen in the KO mice during IAPP infusion suggests that IAPP receptors and/or IAPP post-receptor signaling pathways are up-regulated in mice lacking endogenous IAPP.

A majority of patients with pancreatic cancer have obstructive jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these patients is associated with significant morbidity. Uncoupling protein 2 (UCP2) has been proposed to regulate energy expenditure and promote liver vulnerability. The effects of obstructive jaundice on muscle glucose metabolism and expression of UCP2 in liver and muscle are unknown.Rats were operated with bile duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and muscle. Simultaneously, insulin-stimulated glucose transport and glycogen synthesis in skeletal muscle were analyzed in vitro.The jaundiced rats lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold in liver but not in muscle in jaundiced rats compared to pair-fed controls. The jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or enhanced insulin action on skeletal muscle glucose transport and glycogen synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats.Experimental obstructive jaundice in the rat is associated with increased liver expression of UCP2, rapid weight loss, and intact insulin action on skeletal muscle glucose metabolism. Obstructive jaundice, by upregulated liver UCP2, may contribute to the cachexia and high surgical morbidity observed in these patients, but not to skeletal muscle insulin resistance in pancreatic cancer patients.

Maintenance of intestinal integrity is essential after major abdominal surgery in malnourished subjects. The purpose of this experimental study was to investigate factors affecting small-bowel mucosa permeability in vitro in the immediate postoperative period in starved rats.Male Wistar rats were randomly placed in five groups: Controls, Anesthesia, Resection, Starvation, and Starvation + resection. Controls consisted of fed rats. Anesthesia was induced intraperitoneally with xylazine and ketamine. Resection was 5 cm of the mid-jejunum, and the starvation period was 48 h. Two hours after surgery stripped mucosal segments from the jejunum and the ileum were mounted in Ussing chambers, and the transmucosal permeation of 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and dextran (40,000 Da) was studied for 120 min while electrophysiology was monitored.Starvation increased permeability to 51Cr-EDTA in both the jejunum and ileum. In the jejunum permeability was further increased by starvation + resection. Resection or anesthesia alone did not increase permeability. The villous height in the jejunum was reduced by starvation. Mucosal permeability was correlated to the change in transepithelial resistance during experiments.Starvation was the main cause of increased mucosal permeability in both intestinal segments of the rat, but surgical trauma had an additive effect, which was most pronounced in the jejunum.