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Objectives: The aim of this study was to determine if hypophosphatemia is more common in patients with severe alcohol-induced acute pancreatitis (AAP)., Methods: This is a retrospective, single institution, cohort study that analyzed 147 patients admitted to the hospital for AAP. Multivariate logistic regression was used to determine if hypophosphatemia would be related to clinical outcomes of disease severity., Results: Hypophosphatemia was more common in patients with severe AAP at admission; in addition, all patients with severe AAP (100%) eventually developed hypophosphatemia during admission, relative to those with mild (43%) and moderately severe (54%) AAP. The magnitude of the lowest phosphate measurement obtained during admission was lower in patients with severe AAP (mean, 1.5 mg/dL, standard deviation [SD], 0.5 mg/dL) relative to those with mild (mean, 2.6 mg/dL; SD, 0.9 mg/dL) and moderately severe (mean, 2.3 mg/dL; SD, 0.9 mg/dL) AAP (P < 0.001). Finally, patients who developed hypophosphatemia during admission were more likely to require intensive care unit admission (P < 0.001), vasopressors (P = 0.01), or intubation (P = 0.003)., Conclusions: Hypophosphatemia is more common and of greater magnitude in patients admitted to the hospital with severe AAP. In addition, patients with severe AAP who develop hypophosphatemia during admission are more likely to have poorer clinical outcomes., Competing Interests: A.F. has a patent for a high phosphate solution that is currently under investigation for use in pancreatitis. The other authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: The role of fatty acid ethyl esters (FAEEs) during human alcoholic pancreatitis is unknown. We compared FAEEs levels with their nonesterified fatty acids (NEFAs) precursors during alcohol intoxication and clinical alcoholic pancreatitis. The pathophysiology underlying FAEEs increase and their role as diagnostic biomarkers for alcoholic pancreatitis was investigated., Methods: A prospective blinded study compared FAEEs, NEFAs, and ethanol blood levels on hospitalization for alcoholic pancreatitis (n = 31), alcohol intoxication (n = 25), and in normal controls (n = 43). Serum FAEEs were measured at admission for nonalcoholic pancreatitis (n = 75). Mechanistic cell and animal studies were done., Results: Median FAEEs were similarly elevated during alcohol intoxication (205 nmol/L; 95% confidence interval [CI], 71.8-515 nmol/L, P < .001) and alcoholic pancreatitis (103.1 nmol/L; 95% CI, 53-689 nmol/L, P < .001) vs controls (1.7 nmol/L; 95% CI, 0.02-4.3 nmol/L) or nonalcoholic pancreatitis (8 nmol/L; 95% CI, 1.1-11.5 nmol/L). Alcoholic pancreatitis increased serum NEFAs (1024 ± 710 μmol/L vs 307 ± 185 μmol/L in controls, P < .05). FAEEs comprised 0.1% to 2% of the parent NEFA concentrations. FAEES correlated strongly with NEFAs independent of ethanol levels in alcoholic pancreatitis but not during alcohol intoxication. On receiver operating characteristic curve analysis for diagnosing alcoholic pancreatitis, the area under the curve for serum FAEEs was 0.87 (95% CI, 0.78-0.95, P < .001). In mice and cells, alcohol administration transiently increased all FAEEs. Oleic acid ethyl ester was the only FAEE with a sustained increase up to 24 hours after intraperitoneal oleic acid plus ethanol administration., Conclusions: The sustained, alcohol-independent, large (20- to 50-fold) increase in circulating FAEEs during alcoholic pancreatitis results from their visceral release and mirrors the 2- to 4-fold increase in parent NEFA. The large areas under the curve of FAEEs on receiver operating characteristic curve analysis supports their role as alcoholic pancreatitis biomarkers., (Copyright © 2021 AGA Institute. All rights reserved.)

Background: IgG4-related disease (IgG4-RD) is a systemic inflammatory disease, which includes type 1 autoimmune pancreatitis (AIP). Interleukin-35 (IL-35) exhibits immunosuppressive effects in several autoimmune diseases. However, the expression of IL-35 had not been reported so far in type 1 AIP. We evaluated the association between IL-35 and several cytokines, which mediate the function of Tregs in type 1 AIP., Methods: Plasma was collected from patients with type 1 AIP, alcoholic chronic pancreatitis (ACP), and healthy controls (HC) and assayed for cytokine expression. Total mRNA separated from peripheral blood was isolated from naïve Tregs (nTregs) and effector Tregs (eTregs). EBI3 and IL-12p35 gene expressions were tested in these cells by quantitative PCR. In addition, expression of IL-35 subunits in the pancreatic tissues of patients with type 1 AIP and ACP was analyzed by immunohistochemistry., Results: IL-35 was significantly elevated in type 1 AIP (n = 32) plasma compared with ACP (n = 16) and HC (n = 22), but IL-27 was not. We also detected many cells expressing both EBI3 and IL-12p35 in type 1 AIP tissues. Moreover, in peripheral blood lymphocyte, the percentage of nTregs and eTregs of CD4 + T cells in patients with type 1 AIP (n = 14) compared with HC (n = 15) was significantly decreased and increased, respectively. There were no significant differences of gene expression in patients with type 1 AIP and HC., Conclusions: This study identified elevated expression of plasma IL-35 and tissue IL-35 subunits in patients with type 1 AIP. This might lead to inflammation suppression via activated eTregs. IL-35 might be associated with this anti-inflammatory role, especially against the Th2 response through several cytokines and the differentiation of Tregs in type 1 AIP.

Background: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker associated with inflammatory and certain malignancies. Earlier we have shown that plasma suPAR (P-suPAR) predicts severity of acute alcohol-induced pancreatitis (AAP) on admission. Our aim was to investigate whether P-suPAR levels predict AAP recurrences or mortality during long-term follow-up after first AAP., Methods: Eighty-three patients (median age 47.5, range 25-71 years) suffering their first AAP during 2001-2005 were recruited and followed prospectively for 9 years with a median follow-up time of 7.0 (range 0.3-9.8) years. P-suPAR was measured by enzyme-linked immunosorbent assay (ELISA) from the samples taken at follow-up visits. Survival was registered in November 2014., Results: P-suPAR level on admission or after recovery of the first AAP did not predict the recurrence of AAP. However, higher P-suPAR measured after recovery of first AAP (3.6 vs. 2.9 ng/mL) predicted mortality during follow-up period (hazard ratio 1.48, p = .008). Cut-off value for P-suPAR indicating a higher risk for 10-year mortality resulted a value of ≥3.4 ng/mL. When adjusted for other covariates, P-suPAR above cut-off level retained its statistical significance as an independent factor., Conclusions: P-suPAR level on admission or after recovery of the first AAP does not predict the recurrence of AAP during long-term follow-up. However, P-suPAR ≥3.4 mg/mL measured after recovery from first AAP is associated with an increased risk of 10-year mortality as an independent factor. This can be used to detect patients with highest risk after AAP, in order to focus the preventive healthcare actions., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Acute pancreatitis (AP) is a severe disease associated with significant morbidity and mortality. The overall outcome has improved, but specific treatment(s) remains elusive. The challenge is the early identification and treatment of patients who will develop severe acute pancreatitis. Therefore, the aim of the present study is to investigate plasma levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the initial phase of predicted severe acute pancreatitis., Methods: Between June 2014 and January 2016, 64 patients with acute pancreatitis and 36 healthy individuals were included to study. Four blood samples, for serum TWEAK measurement, were taken from each individual in each group. The first measurement was taken from the admission blood sample. The subsequent three samples were taken at 12, 24, and 48 h after the hospital admission., Results: Serum TWEAK levels were significantly higher in patients with acute pancreatitis when compared with healthy controls. TWEAK plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients., Conclusion: Serum TWEAK levels increase progressively with the severity of acute pancreatitis and TWEAK might be a novel early marker of severity in acute pancreatitis.

Objectives: Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) are increased in various inflammatory and infectious diseases. We investigated the activation and prognostic value of plasma suPAR (P-suPAR) in patients experiencing their first acute alcohol pancreatitis (AAP)., Methods: From prospectively collected data, we measured P-suPAR concentrations in 104 patients with AAP during hospitalization and again after discharge., Results: According to the revised Atlanta classification, pancreatitis was moderately severe in 29 (28%) and severe in 6 (6%) patients and these severities were combined for further analysis (non-mild AAP, n = 35; 34%). Median P-suPAR levels were significantly higher in patients with AAP during hospitalization than after discharge (4.8 vs 3.1 ng/mL; P < 0.001) and in non-mild compared to mild AAP (6.2 vs 4.2 ng/mL; P < 0.001). When the analysis was made 1 to 4 days after admission (n = 68), the area under the curve was 0.81 (95% confidence interval, 0.70-0.92). P-suPAR was found to be a better prognostic marker in AAP than C-reactive protein, hematocrit, or creatinine., Conclusions: P-suPAR concentrations are elevated in AAP and correlate with the severity of the disease. These results suggest that P-suPAR may have potential to serve as a novel prognostic marker for AAP severity on admission.

Background: Biomarkers for the early prediction of the severity of acute pancreatitis (AP) are urgently needed for clinical management of the disease. Angiopoietin-2 (Ang-2), one of the autocrine peptides that reduce endothelial permeability, has been found to be associated with various diseases, including inflammatory disorders., Aims: This study aimed to determine whether serum Ang-2 could serve as a noninvasive biomarker for the early prediction of persistent organ failure (POF) in acute pancreatitis., Methods: A total of 120 AP patients were prospectively enrolled at Jinling Hospital. Serum samples were collected on admission. Clinical and laboratory data were recorded. Ang-2 levels were measured by enzyme-linked immunosorbent assay., Results: A total of 37 patients developed POF and were classified as having severe AP (SAP). Ang-2 was significantly higher on admission in patients who developed POF than in those who did not (p < 0.001 for all). Furthermore, receiver operating characteristic (ROC) curve analysis revealed that Ang-2 could distinguish patients who developed POF from mild AP (MAP, area under ROC curve [AUC] = 0.88, 95 % CI 0.78-0.94) and moderately severe AP patients (MSAP, AUC = 0.74, 95 % CI 0.63-0.83). In addition, multivariate logistic regression showed that increased Ang-2 was an independent predictor of developing POF between subgroups with MSAP and SAP (OR 7.2, 95 % CI 2.7-19.4) and among all AP patients (OR 12.1, 95 % CI 4.8-30.3)., Conclusions: Elevated serum Ang-2 levels on admission may be a promising biomarker for the prediction of POF in AP.

Background: The aim of this study was to find out whether pancreatic diseases invalidate the use of CDT for the detection of high alcohol intake and if CDT can distinguish between alcoholic and non-alcoholic pancreatitis., Methods: The study was carried out on 110 patients with pancreatic diseases. Serum CDT was determined using the N Latex CDT test., Results: The mean relative (%) and absolute (mg/L) CDT levels in acute and chronic pancreatitis were significantly higher than in controls and patients with primary pancreatic cancer. No significant difference was found in CDT concentrations between acute and chronic pancreatitis. The relative and absolute CDT concentrations in alcohol-induced pancreatitis were significantly higher compared to the controls and biliary-induced pancreatitis., Conclusions: Acute and chronic alcoholic pancreatitis, but not biliary pancreatitis, may affect CDT levels. Pancreatitis does not invalidate the use of CDT as a marker of alcohol abuse. CDT can be a useful test for distinguishing alcoholic from non-alcoholic pancreatitis. Changes in CDT level indicate disturbances in transferrin glycosylation in the course of alcoholic pancreatic diseases.

Introduction: There are a lot of pathogenic factors involved in development of polyetiologic diseases. Acetylcholine is known as first-order mediator and plays important role in development and maintenance of pathological processes. In this article we provide data on concentration of acetylcholine (Ah) in blood serum of patients with stomach ulcer (SU), duodenal ulcer (DU), alcoholic chronic pancreatitis (ACP) and control group.as well as activity of cholinesterase (Che). The aim of this study was to identify a role played by Ah in pathological process during a disease, that may complicate a course of the disease as poor prognostic factor., Results and Discussion: We found that there are significant differences in Ah concentration and Che activity between SU, DU, ACP and control. In control group we divide concentration of Ah into three groups: low - 0.46 to 1.0 mlMol/l (60% of individuals), moderate - mlMol 02-1,5/I (30%) and high - more than 1.5 Ah mlMol/I (10%)., Conclusion: We suppose that Che activity and Ah concentration depend on localization of pathological process. It is possible that there are hidden differences in Ah concentration and Che activity between GU and DU.

Objectives: Hypertriglyceridemia (HTG) represents a major health problem with prevalence exceeding 30% in the U.S. The present study aims to assess the effect of elevated serum triglyceride (TG) levels on the severity of acute pancreatitis (AP)., Methods: Prospectively enrolled AP patients were categorized into normal, mild, moderate, and severe/very severe categories based on their TG levels and compared in respect to demographics, comorbidities, and clinical outcomes. Multivariate analysis determined whether elevated TG levels were independently associated with persistent organ failure., Results: Two hundred and one out of 400 AP patients had serum TGs measured within 72 h of presentation, of which 115 had normal TG levels and 86 HTG (20 mild, 41 moderate, and 25 severe/very severe). Patients with HTG were of younger age (44 vs. 52 years), predominantly male (65% vs. 45%), obese (57% vs. 34%), diabetic (38% vs. 17%), and developed more frequently persistent organ failure (40% vs. 17%) compared with those with normal TGs (P<0.02). The rate of persistent organ failure increased proportionally with HTG severity grades (17% when normal TGs, 30% in mild, 39% in moderate, and 48% in severe/very severe HTG, Ptrend<0.001). On multivariate analysis controlling for age, gender, body mass index, diabetes, and alcohol etiology, moderate HTG (odds ratio (OR), 2.6; P=0.04) and severe/very severe HTG (OR, 4.9; P=0.009) were independently associated with persistent organ failure., Conclusions: Elevated serum TGs in AP patients are independently and proportionally correlated with persistent organ failure regardless of etiology. TG-mediated lipotoxicity may be an attractive target to design novel interventions for severe AP.

Background: A number of experimental studies have been put forth suggesting an important role of the hemostatic system in acute pancreatitis (AP) in the recent past. However, meaningful studies on clinical values of parameters of the hemostatic system in predicting pancreatitis associated complications are still scarce. In the current investigation, we evaluated the role of D-dimer to predict the severity of acute pancreatitis on day 1 of admission to the hospital., Methods: A total of 160 subjects (75 mild AP + 35 severe AP + 50 healthy controls) were examined in the study. Biochemical and hemostatic parameters were compared between various groups of subjects on day 1 and day 3 of admission to the hospital., Results: Levels of prothrombin time (PT), fibrinogen, D-dimer, and C-reactive protein (CRP) were significantly higher in the severe AP group than in the mild AP group. Antithrombin III (AT III) levels were significantly lower in the severe AP group than in the mild AP group. D-dimer levels were 5 times higher than the reference limit in the severe group and 1.7 times higher than the reference limit in the mild group. This difference was statistically highly significant (< 0.0001). A positive correlation between D-dimer and CRP, D-dimer and fibrinogen, and between D-dimer and PT was recorded., Conclusions: Estimation of the levels of D-dimer on admission day provides an accurate method for the identification of patients who will develop systemic complications in the further course of AP.

Objective: The aim of this study was to investigate the risk factors for acute kidney injury (AKI) in patients with acute pancreatitis (AP)., Methods: Patients with AP were retrospectively divided into AKI group and non-AKI group. To investigate the risk factors for AKI, logistic regression analysis was performed with demography, etiologies, and comorbidities. Mortalities of patients with different body mass indexes were compared., Results: There were 43 patients with AKI and 202 patients without AKI. The risk factor for AKI in AP was hypertriglyceridemia (odds ratio, 2.964; 95% confidence interval, 1.485-5.915; P = 0.007). Forty-two patients developed AKI within the first 48 hours. The mortalities of normal weight, overweight, and obese groups in patients with AKI were 16.7%, 17.4%, and 62.5%, respectively. All the 4 patients who died in the non-AKI group were of normal weight., Conclusions: Hypertriglyceridemia is an independent risk factor for AKI in the early phase of AP. Obesity does not increase mortality of patients without AKI. We hypothesize that the role of pancreatic enzymes on triglyceride accumulated in renal may be an explanation for AKI in the early phase of AP.

Background: We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease., Methods: We performed cohort and mendelian randomization in 86,258 individuals from the Danish general population, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738)., Results: Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein, and fibrinogen and with decreased albumin; coagulation factors II, VII, and X; and pancreatic amylase. The multifactorially adjusted hazard ratio for alcoholic liver cirrhosis comparing the 96%-100% vs 0%-33% YKL-40 percentile categories was 41 (95% CI 14-118). Corresponding ratios were 7.9 (5.1-12) for any alcoholic liver disease, 4.1 (1.7-10) for alcoholic pancreatitis, and 3.4 (1.9-6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations was associated with a multifactorially adjusted observational hazard ratio of 2.8 (2.4-3.3) for alcoholic liver cirrhosis and a corresponding genetic odds ratio of 1.1 (0.7-1.5). Corresponding risk estimates were 2.0 (1.8-2.2) observationally and 1.0 (0.8-1.1) genetically for any alcoholic liver disease, 1.4 (1.1-1.9) observationally and 1.1 (0.8-1.5) genetically for alcoholic pancreatitis, and 1.3 (1.1-1.6) observationally and 1.0 (0.8-1.3) genetically for any pancreatitis. Excessive alcohol consumption combined with YKL-40 concentrations in the top 5% was associated with 10-year risk of alcoholic liver cirrhosis of up to 7% in ever-smokers and 2% in never-smokers., Conclusions: YKL-40 concentration within the top 5% was a marker for alcoholic liver cirrhosis, with no evidence to support a causal relationship., (© 2014 American Association for Clinical Chemistry.)

Objectives: Transabdominal ultrasonography (US) usually reveals diagnosis of biliary acute pancreatitis (AP). Guidelines suggest repeating US in AP patients without cause at first examination. This approach has been poorly investigated, as well as the accuracy of repeated US as compared with that of magnetic resonance cholangiopancreatography. This study aims at evaluating the diagnostic accuracy of repeated US for biliary AP., Methods: The accuracy of each test for diagnosis of biliary AP was evaluated according to the final diagnosis. Comparison between tests was obtained by examining the areas under the receiver operating characteristic curves., Results: Among 155 patients, the etiology was biliary in 52% and alcoholic in 20%. The accuracy of the first US alone and of the 2 combined examinations for a biliary etiology were 66% and 83%, respectively. Comparison of receiver operating characteristic curves showed a better performance of repeated US (difference between areas under the curve, 0.135; 95% confidence interval, 0.02-0.24; P = 0.021). Magnetic resonance cholangiopancreatography had high specificity (93%) but low sensitivity (62%), with 76% accuracy. The accuracy of the combination of the 2 US examinations and of elevated alanine transferase was 87%., Conclusions: Repeated US is effective for biliary AP diagnosis. The combination of repeated US examinations and biochemical tests seems an effective approach, whereas magnetic resonance cholangiopancreatography might be restricted to selected cases.

Aim: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN)., Methods: Forty patients with mild AP, 40 patients with alcoholic CP, 33 patients with WOPN and 40 healthy subjects were examined. Serum concentrations of platelet derived growth factor BB (PDGF-BB), transforming growth factor β-1 (TGFβ-1), chemerin and high-mobility group box chromosomal protein 1 (HMBG1) were assayed by enzyme linked immunosorbent assay., Results: Patients with mild AP and those with WOPN had significantly lower serum levels of PDGF-BB compared to healthy subjects (4.0 ± 0.61 ng/mL vs 6.2 ± 0.76 ng/mL, P = 0.027, and 1.60 ± 0.31 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001, respectively), while CP was associated with higher serum levels of PDGF-BB (12 ± 1.3 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001). Circulating TGFβ-1 and chemerin levels were elevated in CP patients (57 ± 3.6 ng/mL vs 39 ± 3.6 ng/mL, P < 0.001 and 73 ± 7.2 ng/mL vs 48 ± 2.3 ng/mL, P < 0.001, respectively), but not in patients with AP and WOPN. No significant changes in serum HMBG1 levels were found either in patients with AP, WOPN or CP., Conclusion: The serum levels of some growth factors and cytokines differ significantly in AP, WOPN and CP. These data suggest that selected growth factors and cytokines may be considered as potential diagnostic biomarkers in patients with pancreatic diseases.

Background/aims: To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice., Methods: A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups., Results: The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052)., Conclusions: Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.

Introduction: Acute pancreatitis occurs as a result of autodigestive activation of pancreatic proenzymes, within the parenchyma of the glands., Objective: The goal of the work was to establish possible connection of etiology and severity of the acute pancreatitis and biohumoral parameters, ultrasound and CT., Methods: The study included 273 patients with pancreatitis, classified by Ranson's score, according to degree of severity and etiology, whose biohumoral parameters were correlated with each other, and with the ultrasound and CT findings., Results: The values of amylase and ALT were significantly higher in the severe form of pancreatitis and biliary etiology compared to etilic (p < 0.05).The ratio of AST/ALT was significantly higher in the group of etilic compared to biliary etiology (p < 0.05). LDH was significantly higher in the severe form group compared to moderate form of pancreatitis (p < 0.01). Cholesterol was significantly higher in the group of biliary compared to the group of etilic pancreatitis (p < 0.05). There was a negative low correlation between the value of calcium ions in the plasma and CT analysis (p = 0.05). Low degree negative correlation between the value of calcium ions and ultrasound analysis was established (p = 0.0001)., Conclusion: There was a negative correlation between the level of ionized calcium in the blood and the degree of the acute pancreatitis by the Balthazar score. Mean value of alpha amylase, total value of cholesterol and ALT were significantly higher in the group of biliary compared to the group of etilic acute pancreatitis. The average values of the alpha amylase, LDH and ALT were significantly higher in the group of severe form of the acute pancreatitis compared to the group of moderate form. The ratio AST/ALT was significantly higher in the group of etilic than in the group of biliary pancreatitis.

The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset of alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated the ability of acinar cells to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and evaluated acinar cell necrosis in an animal model of AP and human samples. Rats were fed either an ethanol-containing or control diet for 14 weeks and killed 3 or 24 h after a single lipopolysaccharide (LPS) injection. Inflammasome components and necro-inflammation were evaluated in acinar cells by immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure enhanced acinar cell-specific production of TNFα, IL-6, MCP-1 and IL-10, as early as 3 h after LPS, whereas IL-18 and caspase-1 were evident 24 h later. Alcohol enhanced LPS-induced TNFα expression, whereas blockade of LPS signaling diminished TNFα production in vitro, indicating that the response of pancreatic acinar cells to LPS is similar to that of immune cells. Similar results were observed from acinar cells in samples from patients with acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased systemic levels of HMGB1 and LDH were observed, indicating that this strong systemic inflammatory response is associated with little pancreatic necrosis. These results suggest that TLR-4-positive acinar cells respond to LPS by activating the inflammasome and producing pro- and anti-inflammatory mediators during the development of mild, sub-clinical AP, and that these effects are exacerbated by alcohol injury.

Purpose of Review: This study reviews recent developments concerning the effects of alcohol on plasma triglycerides. The focus will be on population, intervention and metabolic studies with respect to alcohol and plasma triglycerides., Recent Findings: Alcohol consumption and fat ingestion are closely associated and stimulated by each other via hypothalamic signals and by an elevated cephalic response. A J-shaped relationship between alcohol intake and plasma triglycerides has been described. A normal body weight, polyphenols in red wine and specific polymorphisms of the apolipoprotein A-V and apolipoprotein C-III genes may protect against alcohol-associated hypertriglyceridemia. In contrast, obesity exaggerates alcohol-associated hypertriglyceridemia and therefore the risk of pancreatitis., Summary: High alcohol intake remains harmful since it is associated with elevated plasma triglycerides, but also with cardiovascular disease, alcoholic fatty liver disease and the development of pancreatitis. Alcohol-induced hypertriglyceridemia is due to increased very-low-density lipoprotein secretion, impaired lipolysis and increased free fatty acid fluxes from adipose tissue to the liver. However, light to moderate alcohol consumption may be associated with decreased plasma triglycerides, probably determined by the type of alcoholic beverage consumed, genetic polymorphisms and lifestyle factors. Nevertheless, patients should be advised to reduce or stop alcohol consumption in case of hypertriglyceridemia.

Aim: To investigate whether enteroviral infection might trigger acute pancreatitis in patients made susceptible due to high alcohol consumption., Methods: Patients with alcohol-induced acute pancreatitis were analyzed for signs of simultaneous or preceding enteroviral infection. We studied the serum samples of 40 patients hospitalized for alcohol-induced acute pancreatitis and 40 controls recruited from an alcohol detoxification center. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus RNA and diagnose acute viremia. Immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) enteroviral antibodies were measured using enzyme immunoassay to detect subacute and previous infections. The samples were considered positive when the antibody titers were ≥ 15 IU. Furthermore, using RT-PCR, we studied pancreatic biopsy samples obtained during surgery from nine patients with chronic pancreatitis, one patient with acute pancreatitis and ten control patients with pancreatic carcinoma for evidence of persisting enteroviral RNA in the pancreatic tissue., Results: No enterovirus RNA indicating acute viremia was detected by RT-PCR in the serum samples of any patient or control. A high incidence of positive antibody titers was observed in both study groups: IgM antibodies had positive titers in 5/40 (13%) vs 4/40 (10%), P = 0.723; IgG in 15/40 (38%) vs 19/40 (48%), P = 0.366; and IgA in 25/40 (63%) vs 33/40 (83%), P = 0.045, patients and controls, respectively. Ten (25%) patients had severe pancreatitis and two (5%) required treatment in intensive care. The median length of hospitalization was 7 d (range: 3-47 d). The severity of acute pancreatitis or the length of hospitalization was not associated with enteroviral IgM, IgG or IgA antibodies. Five pancreatic biopsy samples tested positive with RT-PCR, three (8%) in the control group and two (5%) in the patient group (P = 0.64)., Conclusion: The rate of enteroviral infection is not increased in patients with alcohol-induced acute pancreatitis when compared to alcoholics with similar high alcohol use.

In order to investigate an association between alcohol consumption and lysosomal cysteine protease induced pancreatic injury and preventive effect of gallic acid as dose-dependent, we determined myeloperoxidase and malondialdehyde levels, serum amylase activities and cathepsin B and L activities in the cytosolic and lysosomal fractions of pancreatic tissue in the ethanol (8 g/kg) and ethanol plus gallic acid (at different doses 50, 100 and 200 mg/kg) given rats. Absolute ethanol (8 g/kg) was given by oral gavage. Gallic acid was dissolved in the saline (2 ml/kg) and administered before 30 min the oral administration of ethanol. Pancreatic myeloperoxidase and also malondialdehyde levels and serum amylase activities were measured. Besides, histological investigations were made. Cathepsin B activities in the cytosolic fraction were decreased by gallic acid (200 mg/kg) and increased in ethanol given rats. Cytosolic/lysosomal ratio of cathepsin B and L were found to be low in the all doses of gallic acid as compared to ethanol group. Serum amylase, pancreatic myeloperoxidase activities and malondialdehyde levels in the ethanol group were higher than in the control group. These were not statistically significant for myeloperoxidase and malondialdehyde. Also, our histopathologic results indicated that ethanol administration increased pancreatic tissue injury. Gallic acid especially at 200 mg/kg improved ethanol-mediated pancreatic tissue damage.In conclusion, gallic acid treatments were decreased release of lysosomal cathepsin B and L enzymes into cytoplasmic fraction and prevented alcohol mediated pancreatic tissue injury. Preventive effect of gallic acid might be dose-dependent.

Background & Aims: We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis., Methods: We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed for 6 months while receiving either antioxidant therapy (Antox version 1.2, Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/day). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative assessments of clinical and diary pain scores, scores on quality-of-life tests (the European Organization for Research and Treatment of Cancer [EORTC-QLQ-C30], Quality of Life Questionnaire-Pancreatic modification [QLQ-PAN28], European Quality of Life questionnaire [EuroQOL EQ-5D], and European Quality of Life questionnaire - Visual Analog Score [EQ-VAS]), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively defined by protocol., Results: After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (-0.36; 95% confidence interval [CI], -1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group and 2.93 for the antioxidant group, a difference of 0.11; 95% CI, 1.05-0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, β-carotene, and selenium were increased significantly in the antioxidant group., Conclusions: Administration of antioxidants to patients with painful chronic pancreatitis of predominantly alcoholic origin does not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Chemerin is a potent chemoattractant for chemokine-like receptor 1 expressing cells and is involved in inflammatory and immune processes that play an important role in chronic pancreatitis., Aim: To test the hypothesis that serum chemerin concentration may be affected in chronic pancreatitis patients and that chemerin can influence the course of chronic pancreatitis by increasing profibrotic cytokine production., Methods: Serum concentrations of chemerin and the major cytokines involved in pancreatic fibrosis such as platelet-derived growth factor BB and transforming growth factor β-1 were determined by ELISA in samples from 40 nondiabetic and 28 diabetic male patients with chronic pancreatitis of alcoholic origin and 40 age-matched healthy controls., Results: Serum concentrations of chemerin were increased both in nondiabetic and diabetic chronic pancreatitis patients compared to controls. Moreover, in chronic pancreatitis patients a positive correlation was found between serum chemerin and platelet-derived growth factor BB as well as transforming growth factor β-1 concentrations., Conclusions: The results indicate for the first time that: (a) chronic pancreatitis in humans is associated with an increased serum chemerin concentration and (b) serum chemerin concentration correlates with serum concentrations of the major profibrotic cytokines. Elevated level of chemerin, by stimulating macrophage infiltration of the pancreas, might lead to overproduction of platelet-derived growth factor BB and transforming growth factor β-1 and, consequently, to pancreatic fibrosis., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Several studies suggest that cytokines and neutrophils play an important role in the pathogenesis of acute pancreatitis (AP). The AIM OF THE STUDY was to assess the systemic release of proinflammatory cytokines and WBC (white blood cells) count with differential in patients with acute alcoholic pancreatitis (AAP) and to characterize the differences between patients with mild and severe forms of the disease., Material and Methods: Thirty-five patients with the mild form of acute alcoholic pancreatitis (MAAP) were compared to 11 patients with severe acute alcoholic pancreatitis (SAAP). Serum levels of IL-6, IL-8, IL-12p40 and WBC differential count were measured every second day during the first week after admission., Results: During the course of the study, the average level of IL-6 was significantly (p<0.05) higher in patients with SAAP than in patients with the mild form of the disease (MAAP). Serum levels of IL-8 and IL-12p40 on admission were higher in patients with SAAP than in patients with MAAP but the difference was not statistically significant. Of all the types of WBCs, neutrophils were significantly (p<0.05) elevated the entire time in SAAP patients when compared to patients with MAAP on 5th and 7th day from admission to hospital., Conclusions: Patients with SAAP had significantly higher proinflammatory cytokine IL-6 levels and neutrophil counts than patients with MAAP. The results suggest that proliferation and overstimulation of this subset of leukocytes might contribute to the development of the systemic inflammatory response in patients with SAAP.

Background/aims: Hyperlipidemia is one known etiology of acute pancreatitis. Alcohol use is known to induce changes in lipid metabolism and might alter the serum lipid and fatty acid profile. We hypothesized that these changes may explain individual susceptibility of developing acute pancreatitis. We compared lipid and fatty acid profiles of patients with acute alcoholic pancreatitis and alcoholic controls., Methods: 19 patients with their first alcoholic pancreatitis and 20 controls were included. Late follow-up samples were obtained from 16 patients. Serum lipids were analyzed enzymatically and the fatty acid profile using gas chromatography., Results: The concentrations of serum total cholesterol, LDL-cholesterol and HDL-cholesterol were markedly lower in patients than in controls during the acute disease but normalized after follow-up. Patients had statistically significantly lower fatty acid proportions of saturated C14:0, polyunsaturated C18:2, C18:3 and C20:3 of the n-6-series and C18:3 of the n-3-series than controls. In contrast, patients had higher percentages of saturated C16:0 and monounsaturated C18:1n9 fatty acids than controls. Mead acid, C20:3n9, marker of essential fatty acid deficiency, was lower in patients than in controls. C14:0, C20:3n6, C18:3n3 and C20:3n9 remained altered after follow-up., Conclusion: Serum lipid and fatty acid levels were significantly altered during the acute disease and returned toward normal after 18-24 months, suggesting that the changes are secondary to acute pancreatitis. They are unlikely to be the much sought 'trigger factor' of pancreatic necro-inflammation. However, further studies are warranted to fully establish this point., (Copyright © 2012. Published by Elsevier B.V.)

Aims: Our aim was to investigate plasma amino acid levels in chronic pancreatitis (CP) patients and examine their relationship with exocrine insufficiency., Methods: Thirty-nine patients with alcoholic CP and 20 healthy controls were examined. CP patients were divided into an exocrine normal group (n = 28) and an exocrine insufficiency group (n = 11). Selected clinical and laboratory values were compared among the three groups, and the effect of an elemental diet was observed in 6 patients of the exocrine insufficiency group., Results: Total amino acid concentration was significantly higher in the control group than in the exocrine normal group and exocrine insufficiency group (p = 0.032, p = 0.020). In the exocrine insufficiency group, significant reductions in the concentrations of serum histidine and methionine were found compared with the control group and exocrine normal group (histidine: p = 0.032, p = 0.045; methionine: p = 0.043, p = 0.049). In the exocrine normal group and exocrine insufficiency group, significant elevation in the concentration of serum glutamate was found compared with the control group (p = 0.036, p = 0.029). Elemental diet improved these amino acid concentrations., Conclusion: Patients with CP exhibit alterations in the levels of several amino acids, such as histidine, methionine, and glutamate. These amino acid deficiencies seem to correlate with exocrine insufficiency and be improved by an elemental diet., (Copyright © 2012 S. Karger AG, Basel.)

Context: Alcoholism may interfere with nutritional status, but reports are often troubled by uncertainties about ingested diet and organ function, as well as by ongoing abuse and associated conditions., Objective: To identify nutritional and body compartment changes in stable alcoholics without confounding clinical and dietetic variables, a prospective observational pilot study was designed. Three well-matched populations were considered: subjects with chronic alcoholic pancreatitis, alcoholics without visceral disease, and healthy never-drinking adults (controls)., Methods: Subjects (n = 60) were asymptomatic males with adequate diet, no superimposed disease or complication, and alcohol-free for at least 6 months. After exclusions, 48 patients were compared. Variables encompassed dietary recall, bioimpedance analysis, biochemical profile and inflammatory markers. Main outcome measures were body fat, lean body mass, serum lipids, C-reactive protein, and selected minerals and vitamins., Results: Both alcoholic populations suffered from reduced lean body mass (P = 0.001), with well-maintained body fat.Magnesium was depleted, and values of vitamin D and B12 correlated with alcohol abuse. LDL and total cholesterol was increased in alcoholics without pancreatitis (P = 0.04), but not in those with visceral damage. C-reactive protein and serum amyloid A correlated with duration of excessive drinking (P = 0.01)., Conclusions: Undernutrition (diminished lean body mass, risk of magnesium and vitamin deficiencies) contrasted with dyslipidemia and increased cardiovascular risk. This second danger was masked during chronic pancreatitis but not in alcoholics without visceral disease. Further studies should focus special requirements of this population.

Background: Oxidative stress-induced free radicals have been implicated in the pathology of chronic pancreatitis (CP)., Aim: We aimed to estimate oxidative stress and antioxidant status in tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) and correlate with zinc status., Methods: One hundred and seventy-five CP patients (91 TCP, 84 ACP) and 113 healthy subjects were prospectively studied. Disease characteristics and imaging features were recorded. Erythrocyte reduced glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), plasma vitamin C, and erythrocyte thiobarbituric acid reactive substance (TBARS) were estimated by spectrophotometry. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry., Results: Enhanced lipid peroxidation with concomitant decrease in antioxidant status was observed in both TCP and ACP patients (p < 0.05). The findings were comparable in both diabetic and non-diabetic CP patients. Significantly, lower plasma vitamin C and elevated levels of erythrocyte TBARS was noted in TCP as compared to ACP patients. The erythrocyte zinc significantly correlated with SOD activity (r = 0.450, p < 0.001)., Conclusions: Our study corroborates the role of oxidative stress in CP and suggests some differences in oxidative status in TCP and ACP patients. Zinc deficiency appears to affect oxidative status in CP patients.

Context: Dietary proteins and amino acids can modulate pancreatic function., Objective: Our aim was to estimate the levels of plasma amino acids in chronic pancreatitis patients and study their relationship with disease characteristics as well as exocrine and endocrine insufficiency., Patients: One hundred and seventy-five consecutive adult patients with chronic pancreatitis: 84 patients with alcoholic chronic pancreatitis and 91 patients with tropical chronic pancreatitis. One hundred and thirteen healthy controls were also studied., Design: Prospective study., Main Outcome Measures: Disease characteristics and imaging features were recorded. Plasma-free amino acid levels were estimated using reverse-phase high-performance liquid chromatography. Polyclonal antibody ELISA was used to assess pancreatic fecal elastase-1., Results: The majority of the plasma free amino acid levels decreased in chronic pancreatitis patients whereas glutamate, glycine, proline and lysine were elevated as compared to the controls. Multivariate logistic regression analysis revealed that the decrease in branched chain amino acid concentration was significantly associated with the presence of diabetes and low fecal elastase-1. In addition, a significant positive correlation was observed between branched chain amino acids and pancreatic elastase-1 (rs=0.724, P<0.001)., Conclusion: Reductions of plasma amino acid levels are seen in chronic pancreatitis, particularly sulphur containing amino acids and branched chain amino acids. Selective amino acid deficiencies seem to correlate with exocrine and endocrine insufficiency.

Background: In vitro studies suggest that platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β1 (TGF-β1) play an important role in pancreatic fibrosis. The aim of this study was to evaluate serum PDGF-BB and TGF-β1 concentrations in patients with chronic pancreatitis (CP)., Methods: Forty male patients with a history of alcoholic CP and 35 age-matched healthy subjects were examined. Serum concentrations of PDGF-BB, TGF-β1, laminin and hyaluronic acid were determined by ELISA assay. Additionally, we determined serum concentrations of PDGF-BB and TGF-β1 in patients with functional dyspepsia, ulcerative colitis and Crohn's disease., Results: Patients with advanced CP had significantly higher serum PDGF-BB and TGF-β1 concentrations compared to control subjects. A strong positive correlation between serum PDGF-BB and TGF-β1 concentrations was found in patients with CP. Serum laminin and hyaluronic acid were also elevated in patients with CP. No increase in serum PDGF-BB and TGF-β1 concentrations was found in patients with functional dyspepsia, ulcerative colitis or Crohn's disease., Conclusion: The obtained results indicate for the first time that serum levels of PDGF-BB are elevated in patients with CP. However, ROC curve analysis suggests that PDGF-BB is not superior to laminin as a potential marker of advanced CP., (Copyright © 2011 S. Karger AG, Basel.)

Objectives: The mechanisms initiating pancreatitis in patients with chronic alcohol abuse are poorly understood. Although alcohol feeding has been previously suggested to alter cholinergic pathways, the effects of these cholinergic alterations in promoting pancreatitis have not been characterized. For this study, we determined the role of the cholinergic system in ethanol-induced sensitizing effects on cerulein pancreatitis., Methods: Rats were pair-fed control and ethanol-containing Lieber-DeCarli diets for 6 weeks followed by parenteral administration of 4 hourly intraperitoneal injections of the cholecystokinin analog, cerulein at 0.5 μg/kg. This dose of cerulein was selected because it caused pancreatic injury in ethanol-fed but not in control-fed rats. Pancreatitis was preceded by treatment with the muscarinic receptor antagonist atropine or by bilateral subdiaphragmatic vagotomy. Measurement of pancreatic pathology included serum lipase activity, pancreatic trypsin, and caspase-3 activities, and markers of pancreatic necrosis, apoptosis, and autophagy. In addition, we measured the effects of ethanol feeding on pancreatic acetylcholinesterase activity and pancreatic levels of the muscarinic acetylcholine receptors m1 and m3. Finally, we examined the synergistic effects of ethanol and carbachol on inducing acinar cell damage., Results: We found that atropine blocked almost completely pancreatic pathology caused by cerulein administration in ethanol-fed rats, while vagotomy was less effective. Ethanol feeding did not alter expression levels of cholinergic muscarinic receptors in the pancreas but significantly decreased pancreatic acetylcholinesterase activity, suggesting that acetylcholine levels and cholinergic input within the pancreas can be higher in ethanol-fed rats. We further found that ethanol treatment of pancreatic acinar cells augmented pancreatic injury responses caused by the cholinergic agonist, carbachol., Conclusion: These results demonstrate key roles for the cholinergic system in the mechanisms of alcoholic pancreatitis., (Copyright © 2010 by the Research Society on Alcoholism.)

Objectives: Acute pancreatitis (AP) is a severe inflammatory disease with high mortality and morbidity rates. We have previously demonstrated that resistin may represent an early marker of inflammation in AP. It was also revealed that ghrelin may have anti-inflammatory potential. However, the role of adipohormones in AP-resistin and ghrelin as well as the proinflammatory cytokine interleukin (IL)-18-has not yet been fully elucidated., Methods: The study group comprised 32 patients with alcoholic AP and 30 controls matched for age, sex, and body mass index (BMI). In all cases AP was classified as grade C according to Balthazar's computed tomography (CT) score and as severe (3 points) according to Ranson's criteria. Serum levels of resistin, ghrelin, and IL-18 were measured on first, third, and fifth day of hospitalization by enzyme-linked immunosorbent assay (ELISA)., Results: On first day of hospitalization the mean serum resistin concentration in AP patients was significantly higher than in controls (P < 0.05) and further increased on third and fifth day of hospitalization (17.4 ± 4.23 ng/ml and 25.8 ± 8.14 ng/ml, respectively). On first day of hospitalization the mean serum IL-18 concentration in AP patients was significantly higher than in controls (P < 0.05), on third day its level further increased, and on fifth day it decreased to a level similar to that observed on admission. The serum ghrelin concentrations on first, third, and fifth day of hospitalization were comparable, and significantly higher than in controls (P < 0.01). Significant correlation between C-reactive protein (CRP) and resistin levels (r = 0.43; P < 0.05) and between CRP and IL-18 (r = 0.58; P <0.05) on day of admission was found., Conclusions: Serum concentration of IL-18 and resistin may contribute to inflammatory response and may be useful as an early marker of inflammation in AP. We also suspect that ghrelin affects the course of AP and plays an important role in inflammatory response.

Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH(-)) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH(-) and hepatic ADH-normal (ADH(+)) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ∼1.5-fold greater in ADH(-) vs. ADH(+) deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH(-) deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: To study the association of binge drinking and the outcomes of severe acute pancreatitis (SAP)., Methods: This retrospective study included 347 patients with first-attack SAP from January 2001 to February 2004. On the basis of the history of binge drinking or not, the patients were divided into the alcohol (n = 77) and the control groups (n = 270). Clinical data of the 2 groups were compared., Results: Patient age and comorbidity were similar between the 2 groups. There were more men (64, 83.1%) than women (13, 16.9%; P < 0.05) in the alcohol and the control groups (111, 41.1%; P < 0.05). The 2 groups had significant differences in admission serum triglyceride levels (5.0 +/- 5.0 vs 3.0 +/- 3.5, P < 0.05), Balthazar computed tomographic score (6.3 +/- 5.4 vs 4.2 +/- 4.5, P < 0.05), and Acute Physiology and Chronic Heath Evaluation II score (19.1 +/- 5.1 vs 16.2 +/- 6.0, P < 0.05). Total mortality and the incidences of complications were higher in the alcohol group than in the control group (P < 0.05)., Conclusions: Binge drinking might be a contributor to the aggravation of first-attack SAP.

Background/aims: Supplementation of n-3 long-chain polyunsaturated fatty acids (LCPUFA) is considered as adjuvant therapy in acute pancreatitis. We investigated plasma fatty acid status in chronic pancreatitis (CP)., Methods: Patients with alcoholic CP (n = 56, gender: 33/23 male/female, age: 60.0 [14.0] years (median [IQR]), who reported giving up alcohol consumption several years ago and 51 control subjects were included into the study. The fatty acid composition of plasma phospholipids (PL), triacylglycerols (TG) and sterol esters (STE) was analyzed., Results: The sum of monounsaturated fatty acids was significantly higher in patients with CP than in controls (PL: 12.83 [3.35] vs. 12.20 [1.95], TG: 40.51 [6.02] vs. 37.52 [5.80], STE: 20.58 [7.22] vs. 17.54 [3.48], CP vs. control, % weight/weight, median [IQR], p < 0.05). Values of arachidonic acid were significantly lower in patients with CP than in controls (PL: 10.57 [3.56] vs. 11.66 [3.25], STE: 8.14 [2.63] vs. 9.24 [2.86], p < 0.05). Values of eicosapentaenoic acid and docosahexaenoic acid did not differ and there was no difference in the ratio of n-3 to n-6 LCPUFA., Conclusion: Our present data do not furnish evidence for the supplementation of n-3 LCPUFA to the diet of CP patients in relatively good clinical condition., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: Homocysteine has been implicated in vascular dysfunction and thrombosis, as well as inflammatory conditions. This study was aimed to find out whether chronic pancreatitis (CP) is associated with hyperhomocysteinemia and derangements of transmethylation and transsulfuration pathways., Methods: We estimated homocysteine and its metabolites in 45 alcoholic CP patients, 45 tropical CP patients, and 48 healthy controls., Results: Significant increases in plasma total homocysteine and decreases in red blood cell folate, reduced glutathione, plasma methionine, cysteine, and urinary inorganic sulfate/creatinine ratio were observed in both alcoholic and tropical CP patients in comparison with healthy controls. Red blood cell glutathione and plasma cysteine levels were significantly lower in alcoholic than in tropical CP patients. However, plasma vitamin B12 levels were comparable between CP patients and controls. No significant differences in these parameters were observed between diabetic patients and nondiabetic patients. Multivariate regression analysis showed a significant negative correlation between homocysteine and folate (r = -0.415, P = 0.001) and a positive correlation between glutathione and cysteine levels (r = 0.37, P = 0.003)., Conclusions: Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in transmethylation and transsulfuration pathways. Low folate levels observed in these patients seem to have a key role in this derangement.

Background: Resistin and visfatin, hormones produced by adipose tissue, have pro-inflammatory potential; however, their role in acute pancreatitis (AP) has been investigated only rarely., Methods: The study group comprised 32 patients with alcoholic AP and 30 controls. In all cases AP was classified as C according to Balthazar's CT score and as severe according to Ranson's criteria. The serum level of visfatin, resistin, and interleukin(IL)-8 immunoassays were measured by ELISA on admission and on the third and fifth day of hospitalization., Results: On the admission day serum resistin and IL-8 concentrations in AP patients were significantly higher than in controls and they further increased on the third and fifth day of hospitalization. On the admission day serum visfatin levels in AP patients were significantly higher than in controls and further increased on the third day of hospitalization. On the fifth day the levels decreased; however, they were still higher than on admission. The correlation between visfatin and resistin as well as between C-reactive protein and visfatin, resistin and IL-8 levels has been found., Conclusion: In the course of AP, visfatin and resistin levels increase in parallel with C-reactive protein. We speculate that those parameters may provide an additional tool for the prognosis and monitoring of AP. and IAP., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: If differences of inflammatory pathways in acute pancreatitis exist for various etiologies, selective and specific antiinflammatory and other modulatory treatment regimens might be indicated. Circulating levels of prominent proinflammatory cytokines IL-6, 8, 18, and TNF-alpha were measured in patients having their first attack of either alcohol- or gallstone-induced acute pancreatitis., Methods: Seventy-five consecutive patients were prospectively included over a 15-month period, sixty of them being either alcohol- or gallstone-induced. All patients were treated according to a standardized algorithm. Blood samples were obtained immediately on admission and, again, at days 1, 2, and 14., Results: A significant effect of the etiology on the levels of IL-8 in the alcohol group as compared to the gallstone group (P=0.003) was found. No etiologic differences were observed for IL-6, IL-18, TNF-alpha, or CRP. Furthermore, no significant differences, either regarding the need for treatment at the intensive care unit or of 30-day mortality, were found., Conclusion: The present study confirms previous findings and supports the hypothesis that, except for IL-8, the biochemical profile and clinical outcome is independent of the underlying etiology. Revealing the complex spatial and temporal profile of proinflammatory cytokine expression in acute pancreatitis is necessary and important for the development of a more targeted rational therapy.

It has been previously shown that alcohol induces the damage of pancreatic parenchyma tissue, but the mechanism of this damage is still poorly understood. Assuming that oxygen radical damage may be the involved, we measured markers of oxidative damage in pancreatic tissue, blood serum, plasma, and whole blood of rats with early-stage alcohol-induced acute pancreatitis. Thirty-eight male Wistar rats were divided into three groups: the control group (group 1), the acute pancreatitis group 1 day (group 2), and 3 days (group 3) after the injection of ethyl alcohol into the common biliary duct, respectively. The levels of Fe in tissue and serum, whole blood viscosity, plasma viscosity, fibrinogen and homocysteine (Hcy) levels, erythrocyte and plasma malondialdehyde (MDA), and tissue and plasma protein carbonyl levels were found to be significantly higher in groups 2 and 3 than in group 1. However, the levels of reduced glutathione (GSH) in tissue and erythrocytes were significantly lower in groups 2 and 3 than in group 1. These results suggest that elevated Fe levels in serum and pancreatic tissue in rats with early-stage alcohol-induced acute pancreatitis is associated with various hemorheological changes and with oxidative damage of the pancreas.

Objective: The aim of this study was to assess serum adiponectin and leptin concentrations in patients with chronic pancreatitis of alcoholic and nonalcoholic origin., Methods: Forty-four male patients with chronic pancreatitis of alcoholic origin and 10 patients of nonalcoholic origin as well 16 healthy subjects were examined. Fasting blood samples were collected. Serum adiponectin, leptin, and insulin concentrations were determined by radioimmunoassay methods., Results: Patients with chronic pancreatitis had lower body mass index values compared with those of control. Nonetheless, there were no differences in serum adiponectin concentration between pancreatitis patients and healthy controls. Pancreatitis patients had lower serum leptin and insulin concentrations than healthy subjects. No difference in serum leptin and insulin concentrations between patients with chronic pancreatitis of alcoholic and nonalcoholic origin was observed. The serum adiponectin/leptin concentration ratio was higher in chronic pancreatitis patients than in control subjects., Conclusions: Chronic pancreatitis in humans (a) is associated with the decrease in serum leptin and insulin concentrations, (b) does not affect serum adiponectin concentration but increases serum adiponectin/leptin concentration ratio, and (c) alters the interrelationship between serum adiponectin and insulin concentrations. Moreover, these results suggest that changes in serum leptin and insulin concentrations are independent on the etiology of chronic pancreatitis.

Aim: To determine the role of acetylcholine (AC), serotonine (5-HT) and cytokines in progression and complications of chronic alcohol pancreatitis (CAP)., Material and Methods: 50 CAP patients were examined in the exacerbation, remission and complications of CAP (48 males, 2 females) aged 30-50 years. Control group consisted of 15 healthy subjects. IL-1beta, IL-6, IL-8, IFN-gamma, TNF-alpha, IL-4 were studied with enzyme immunoassay, 5-HT--with Ch. Sadovanquivad method, AC and activity of cholinesterase (CE) in the blood--by the method of Sh. Hestrin. Pancreatic tissue fibrosis was assessed according to computer tomography findings., Results: Patients with CAP in exacerbation had significant rise of proinflammatory, anti-inflammatory cytokines, AC and 5-HT. In a complicated course of CAP there is a pronounced rise in TNFalpha in normal level of IL-4. CAP patients with destructive changes in the pancreas showed significant rise in the level of AC and 5-HT and lowering of cytokines. CE activity in complicated course of CAP is low this indicating protein-synthetic insufficiency in CAP patients., Conclusion: In CAP the action of 5-HT and AC aims at maintenance of secretory activity of the pancreas. In inflammation participation of neuromediators decreases. Stimulation of pancreatic secretory activity switched to autonomic regulation which is prognostically unfavourable.

Objectives: Serum disialotransferrin is a specific marker of heavy alcohol consumption. We tested its accuracy and probability in detecting alcoholic cause of acute pancreatitis (AP)., Methods: Blood samples from 271 consecutive AP patients, admitted to the Helsinki University Central Hospital emergency unit, were analyzed., Results: The median (range) disialotransferrin value was significantly higher (P = 0.001) in AP patients with alcoholic (n = 172) 1.6% (0.3%-14.4) than with biliary (n = 60) 0.7% (0.3%-1.3%) or other causes (n = 39) 0.8% (0.3%-4.1%). In receiver operating curve analysis, disialotransferrin, as a single analyte, was significantly (P = 0.001-0.0001) more accurate (area under the curve [AUC], 0.88; 95% confidence interval [CI], 0.84-0.92) in detecting alcoholic AP as compared with glutamyl transferase (AUC, 0.51; 95% CI, 0.45-0.57), aspartate aminotransferase (AUC, 0.57; 95% CI, 0.51-0.63), alanine aminotransferase (AUC, 0.63; 95% CI, 0.57-0.69), erythrocyte mean cell volume (AUC, 0.72; 95% CI, 0.67-0.78), amylase (AUC, 0.74; 95% CI, 0.67-0.78), C-reactive protein (AUC, 0.65; 95% CI, 0.59-0.71), and bilirubin (AUC, 0.55; 95% CI, 0.49-0.62). At a disialotransferrin cutoff of 1.2%, giving an 8% false-positive rate, the positive likelihood ratio was 8.47. Thus, a positive disialotransferrin test result, performed within 24 hours of admission, increased the probability of alcoholic AP from pretest 64% to posttest 94%., Conclusions: Disialotransferrin, determined by capillary electrophoresis, is accurate, simple, and a rapid single biomarker of the alcoholic cause of AP.