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Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with organ failures and very high short-term mortality.To assess the incidence and factors predisposing to ACLF in patients with liver cirrhosis hospitalized due to acute gastrointestinal bleeding (GIB).We collected and retrospectively analyzed the data of 89 consecutive patients (59 males (66.2%), median age 53 years (range: 44-62 years), mean Model for End-Stage Liver Disease (MELD) score 14.42 ±6.5, median Child-Turcotte-Pugh score 10 (range: 8-11), and acute GIB (72 variceal bleeding and 17 non-variceal bleeding cases). Acute-on-chronic liver failure was diagnosed based on European Association for the Study of the Liver - Chronic Liver Failure Consortium definition.Twenty-seven (30.33%) patients met the criteria of ACLF during hospitalization: 8 (30%) had ACLF grade 1, 13 (48%) had ACLF grade 2 and 6 (22%) had ACLF grade 3. The most frequent organ failures were respiratory (22 (25%)), kidney (18 (20.23%)) and brain (17 (19.1%)) failure. The MELD score value, creatinine level and presence of hepatic encephalopathy (HE) on admission were significant predictors of ACLF in the multivariate logistic regression model with optimal cutoff point for MELD score of 18.313 and optimal cutoff point for creatinine level of 1.35 mg/dL.In-hospital risk of ACLF in cirrhotic patients hospitalized for acute gastrointestinal hemorrhage is high despite successful arrest of bleeding. Elevated creatinine level, MELD score and the presence of HE on admission are the best predictors of ACLF during hospitalization in such patients.

Purpose: Due to the lack of systematic data on antibiotic sensitivity, the treatment of the highly prevalent and pathogenic Helicobacter pylori (H. pylori) infection still poses a significant problem. Therefore, the aim of our study was to compare the efficacy of the three most commonly used anti-H. pylori therapies in northeastern Poland. Patients and Methods: This was a retrospective, single-center study performed on 289 outpatients with an H. pylori infection. Patients received one of the following three treatment regimens: (1) bismuth quadruple therapy (BQT) for 10 days, (2) metronidazole-based triple therapy (M-TT) for 10 or 14 days, and (3) levofloxacin-based triple therapy (L-TT) for 10 or 14 days. Results: BQT, M-TT, and L-TT accounted for 93.2% of prescribed anti-H. pylori therapies. The overall success rate for all treatment regimens was 84.1% (243/289). The effectiveness of first- and second-line therapy was similar and reached 83.8% and 86.2%, respectively. The efficacy of the individual treatment regimens was as follows: (1) BQT—89.4% (84/94), (2) M-TT—80.6% (112/139) and 78.8% (26/33) for 10 and 14 days, respectively, and (3) L-TT—84.6% (11/13) and 100% (10/10) for 10 and 14 days, respectively. The overall duration of treatment and type and dose of proton pump inhibitor (PPI) had no effect on the treatment efficacy. Conclusions: In the northeastern part of Poland, 10-day BQT and 10- or 14-day L-TT are effective treatment regimens for H. pylori eradication and have appear to be superior to M-TT. Practitioners in our clinic followed mostly local anti-H. pylori therapy guidelines.

Introduction Proton pump inhibitors therapy success in the treatment of gastroesophageal reflux disease (GERD) is a difficult task because the extent of mucosal damage has no relation with the severity of the symptoms. Aim To establish the efficacy of pantoprazole treatment in patients with erosive reflux disease (ERD) and in those with non-erosive reflux disease (NERD), by assessing symptom relief and quality of life. Treatment duration and adverse events associated with pantoprazole treatment were analysed. Material and methods This meta-analysis was based on three multicentre, prospective, open-label, phase IV trials conducted in Slovenia, Poland, and the Russian Federation. In total, 252 patients with GERD were included and treated with pantoprazole 40 mg once daily for 4 or 8 weeks, depending on the fulfilment of predefined healing criteria. Symptoms were assessed by patients on a scale from 0 to 3 and the quality of life on a rating scale from 1 to 10. Results Forty-five percent of patients fulfilled the healing criteria after 4 weeks of treatment, and 70% of patients after 8 weeks of treatment. Patients who failed to reach the healing criteria reported significant reduction of symptoms severity. The response to 8-week treatment was significantly higher in patients with ERD (76%) when compared to patients with NERD (64%). Discontinuation of treatment after 4 weeks was not associated with worsening of symptoms and did not affect quality of life. Pantoprazole treatment was associated with improvement of symptoms and the quality of life of GERD patients over 8 weeks of treatment and showed that GERD patients with persisting symptoms benefit from prolonging treatment to 8 weeks. Treatment with pantoprazole 40 mg was very well tolerated - more than 90% of patients were without adverse events throughout the whole study and only 4 patients discontinued the treatment due to adverse events related to pantoprazole treatment. Conclusions Pantoprazole 40 mg was associated with complete relief of GERD-related symptoms in the majority of patients with ERD and NERD. Furthermore, the severity of symptoms was significantly reduced in patients without complete relief of symptoms. Pantoprazole also continuously improved the quality of life of GERD patients over 8 weeks of treatment and was very well tolerated throughout the whole study. Therefore, this meta-analysis suggests that pantoprazole 40 mg once daily is an effective and well-tolerated choice for providing symptom relief of patients with GERD.

Pancreatic ductal adenocarcinoma is one of the deadliest human neoplasms. Despite the development of new surgical and adjuvant therapies, the prognosis remains very poor, with the overall survival rate not exceeding 9%. There is now increasing evidence that the human microbiome, which is involved in many physiological functions, including the regulation of metabolic processes and the modulation of the immune system, is possibly linked to pancreatic oncogenesis. However, the exact mechanisms of action are poorly understood. Our review summarizes the current understanding of how the microbiome affects pancreatic cancer development and progression. We discuss potential pathways of microbe translocation to the pancreas, as well as the mechanism of their action. We describe the role of the microbiome as a potential marker of pancreatic cancer diagnosis, progression, and survival. Finally, we discuss the possibilities of modifying the microbiome to improve treatment effectiveness for this deadly disease.

Background Cigarette smoke (CS) exerts protective effect against ulcerative colitis. The mechanism of this phenomenon remains unknown. One of the possible explanation by which CS exerts its anti-inflammatory action is modulation of immune system. Therefore, the aim of the study was to evaluate the effect of CS on the course of inflammation and subpopulations of lymphocytes in the blood and colon in mice with dextran sulfate sodium (DSS)-induced colitis. Methods C57BL6/cmdb mice were exposed to CS for 4 weeks. Colitis was induced with 3.5% DSS given for 10 days. Severity of colitis was determined by disease activity index (DAI), body weight changes, and macro- and microscopic characteristics of inflammation. Peripheral subpopulations of lymphocytes were assessed by flow cytometry (blood) or immunohistochemistry (colonic tissue). Results Mice treated with 3.5% DSS developed severe colitis with significantly decreased body weight, increased DAI, and macroscopic and histological features of colonic inflammation. These findings were diminished after concomitant exposure to CS. Mice exposed to DSS alone demonstrated significantly decreased percentage of total CD4+ cells (73.1 vs. 52%, p = 0.0007), accompanied by increase of CD8+ cells (18.4 vs. 39.5%, p = 0.0001). Concomitant CS exposure reversed inappropriate CD4+/CD8+ ratio both in the blood and colon and significantly increased B cell presence in the colon. Conclusions Our study has demonstrated that CS exposure decreases severity of DSS-induced colitis. This phenomenon was accompanied by changes in CD4/CD8 ratio and B cell level in the peripheral blood and colon. These mechanisms may be responsible for protective effect of smoking in ulcerative colitis. Electronic supplementary material The online version of this article (doi:10.1007/s00384-017-2882-9) contains supplementary material, which is available to authorized users.

Background and Aims Therapeutic endoscopy plays a critical role in the management of upper GI (UGI) postsurgical leaks. Data are scarce regarding clinical success and safety. Our aim was to evaluate the effectiveness of endoscopic therapy for UGI postsurgical leaks and associated adverse events (AEs) and to identify factors associated with successful endoscopic therapy and AE occurrence. Methods This was a retrospective, multicenter, international study of all patients who underwent endoscopic therapy for UGI postsurgical leaks between 2014 and 2019. Results Two hundred six patients were included. Index surgery most often performed was sleeve gastrectomy (39.3%), followed by gastrectomy (23.8%) and esophagectomy (22.8%). The median time between index surgery and commencement of endoscopic therapy was 16 days. Endoscopic closure was achieved in 80.1% of patients after a median follow-up of 52 days (interquartile range, 33-81.3). Seven hundred seventy-five therapeutic endoscopies were performed. Multimodal therapy was needed in 40.8% of patients. The cumulative success of leak resolution reached a plateau between the third and fourth techniques (approximately 70%-80%); this was achieved after 125 days of endoscopic therapy. Smaller leak initial diameters, hospitalization in a general ward, hemodynamic stability, absence of respiratory failure, previous gastrectomy, fewer numbers of therapeutic endoscopies performed, shorter length of stay, and shorter times to leak closure were associated with better outcomes. Overall, 102 endoscopic therapy–related AEs occurred in 81 patients (39.3%), with most managed conservatively or endoscopically. Leak-related mortality rate was 12.4%. Conclusions Multimodal therapeutic endoscopy, despite being time-consuming and requiring multiple procedures, allows leak closure in a significant proportion of patients with a low rate of severe AEs.

Objective We aimed to identify the best method of omeprazole (OME) application with respect to intragastric pH, cytochrome P450 2C19 (CYP2C19) genotype and phenotype. Methods The patients with non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively enrolled. After the achievement of endoscopic hemostasis, the patients were randomized to 40-mg intravenous (i.v.) OME bolus injection every 12 h or 8-mg/h continuous i.v. infusion for 72 h after an 80-mg i.v. OME bolus administration. The intragastric pH was recorded for 72 h. The CYP2C19 variant alleles (*2, *3, *17) were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole (5-OH OME) were determined. Results Altogether 41 Caucasians (18 in the OME infusion [OI] group and 23 in the OME bolus [OB] group) were analyzed. The median percentage of time with an intragastric pH > 4.0 was higher in the infusion group than in the OB group over 48 h (100% vs 96.6%, P = 0.009) and 72 h (100% vs 87.6%, P = 0.006), and that at an intragastric pH >6.0 was higher in the OI group than the OB group over 72 h (97.9% vs 63.5%, P = 0.04). Helicobacter pylori infection was correlated with the fastest increase in intragastric pH, especially in the OI group. In both groups, CYP2C19 genotypes (*1/*1, *1/*17, *17/*17) had no essential effect on intragastric pH. Conclusions In patients with NVUGIB, OME i.v. bolus followed by continuous infusion is more effective than OME i.v. bolus every 12 h in maintaining higher intragastric pH, regardless of CYP2C19 genetic polymorphisms. H. pylori infection accelerates the initial elevation of intragastric pH.

Aim We aimed to assess the relationship between procoagulant imbalance and the occurrence of variceal bleeding in patients with liver cirrhosis. Methods We compared the results of chromogenic assay for the functional evaluation of the Protein C anticoagulant pathway (ThromboPath®), thromboelastometry and the levels of factor VII, VIII, and antithrombin in two groups of cirrhotic patients: Group 1 (n = 25) — patients with moderate or large esophageal or gastric varices, who had never experienced acute gastrointestinal bleeding and Group 2 (n = 24) — patients with a history of variceal bleeding. Results Despite the differences in MELD score and the results of basic laboratory tests indicating more severe cirrhosis and suggesting a greater risk of bleeding in Group 2, the results of thromboelastometry did not differ significantly between groups. The ThromboPath® test results [ThP B: 67.8 ± 13.4 versus 59.09 ± 12.4%, p = 0.023] and factor VII level [69.04 ± 24.16 vs 53.54 ± 25.06, p = 0.032] confirmed greater plasma procoagulant activity in Group 1 compared to Group 2. However, there were no statistically significant differences in thrombin generation after activation of the protein C. Plasma of patients in Group 2 was more resistant to anticoagulation with protein C compared to Group 1 (PICI%: 65.58 ± 7.24 versus 55.64 ± 13.07%, p = 0.001). Conclusion The results of our study confirm the lack of influence of coagulation disorders on the occurrence of variceal bleeding. Moreover, the results of ThromboPath® assay indicate hypercoagulability in patients with a history of variceal bleeding and more severe liver cirrhosis, compared to patients who have never bled.

Background Beneficial clinical effects of weight reduction following bariatric therapies is not fully understood and maybe related to the complex interactions between leptin, adiponectin, visfatin, omentin, and ghrelin. The aim of study was to investigate their timeline changes associated with weight reduction and their profile in relation to the type of treatment and its efficacy. Methods Circulating hormones levels were analyzed before and after endoscopic and surgical procedures in 67 obese patients and compared to non-obese healthy controls. Results Obese patients had higher leptin levels and lower levels of adiponectin, visfatin, omentin, and ghrelin than non-obese controls. During the consecutive follow-up visits after treatment, there was a gradual decrease in leptin levels and an increase in adiponectin levels to the levels observed in non-obese. At 50–54 weeks, the ghrelin levels were lower and the levels of adiponectin and visfatin, but not omentin, were higher compared to their baseline values. BMI correlated with ghrelin and leptin levels. The percentage of total weight loss correlated positively with adiponectin levels and negatively with leptin levels. Patients with adequate weight loss had a significantly lower leptin concentration than those with treatment failure. There were timeline variations in hormone levels between endoscopic and bariatric therapies, however there were no significant differences in the median their concentration at 50–54 weeks after therapy. Conclusion Our study supports observations that weight loss itself, rather than the procedure type, is responsible for hormonal variation. The leptin levels reflect the best the body weight changes after bariatric therapies.

In this paper, we present a new brain diagnostic method based on a computer aided multispectral ultrasound diagnostics method (CAMUD). We explored the standard values of the relative time of flight (RIT), as well as the attenuation, ATN, of multispectral longitudinal ultrasound waves propagated non-invasively through the brains of a standard Caucasian volunteer population across different ages and genders. For the interpretation of the volunteers health questionnaire and ultrasound data we explored various clustering and classification algorithms, such as PCA and ANOVA. We showed that the RIT and ATN values provide very good estimators of possible physiological changes in the brain tissue and can differentiate the possible high-risk groups obtained by other groups and methods (Russo et al. [1] ; Lloyd-Jones et al. [2] ; Medscape [3] ). Special attention should be given to the subgroup which included almost 39% of the volunteers. Respondents in this group have a significantly increased minimum ATN value (see Classification Trees). These values are strongly correlated with the identified risk of stroke factors being: age, increased alcohol consumption, cases of heart disease and stroke in the family as already shown by Rusco and as incorporated into Lloyd-Jones et al., “Heart Disease and Stroke Statistics – 2009 Update”, by the American Heart Association (AHA) and American Stroke Association (ASA), as updated recently in the 2015 “Stroke Prevention Guidelines”.

Objective The invasive measurement of hepatic venous pressure gradient is the recommended method for the assessment of portal hypertension. We assessed if the mediators that regulate portal hypertension may be used as noninvasive markers of portal hypertension and liver insufficiency. Materials and methods We explored in prospective, observational study the concentration of endothelin-1, nitric oxide, and transforming growth factor-β1/2 in peripheral and hepatic venous blood; their relationship with the values of portal hypertension and liver insufficiency; and their level changes 4–6 months after non-selective beta-blocker therapy in cirrhotic patients with non-bleeding esophageal varices. Results (1) Cirrhotics have significantly increased peripheral endothelin 1 and decreased transforming growth factor-β1 levels; (2) peripheral levels of all factors correlated significantly with their hepatic levels; (3) after therapy, peripheral endothelin-1 levels significantly increased, but transforming growth factor-β2 levels decreased and were lower in patients with pressure gradient value normalization; (4) before and after therapy, peripheral and hepatic endothelin-1, transforming growth factor-β1/2 levels correlated significantly with liver failure indicators (laboratory parameters, Child-Pough and MELD scores) and pressure gradient values. Conclusions Peripheral endothelin-1 and transforming growth factor-β1 levels, which strongly correlate with their hepatic levels, reflect the stage of portal hypertension and liver insufficiency in cirrhosis.

The exact time of initiation of total enteral nutrition (TEN) in severe acute pancreatitis (SAP) and its influence on the disease outcome are not well known.An analysis of 197 cases with predicted SAP allocated to: group A (n = 97), early TEN (started within the first 48 hours after admission to hospital); and group B (n = 100), delayed TEN (started after 48 hours).Infection of necrosis/fluid collections occurred in 4 patients in group A and 18 patients in group B (P0.05). Respiratory failure and transfer to intensive care unit occurred more frequently in group B than in group A (15 vs 5 and 15 vs 3 patients; P0.05). Multiple-organ failure was observed in 9 patients in group A and 16 patients in group B (P0.05). Seven patients in group A and 11 patients in group B underwent surgery (P0.05). All 9 reported deaths occurred in group B (P0.05). The time to start TEN was a predictor of infected necrosis/fluid collection (odds ratio, 4.09; P = 0.028).Delayed compared to early TEN is associated with higher mortality, increased frequency of infected necrosis/fluid collections, respiratory failure, and a need for intensive care unit hospitalization. Enteral nutrition in SAP should be started within 48 hours after admission to hospital.

We aimed to identify the best method of omeprazole (OME) application with respect to intragastric pH, cytochrome P450 2C19 (CYP2C19) genotype and phenotype.The patients with non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively enrolled. After the achievement of endoscopic hemostasis, the patients were randomized to 40-mg intravenous (i.v.) OME bolus injection every 12 h or 8-mg/h continuous i.v. infusion for 72 h after an 80-mg i.v. OME bolus administration. The intragastric pH was recorded for 72 h. The CYP2C19 variant alleles (*2, *3, *17) were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole (5-OH OME) were determined.Altogether 41 Caucasians (18 in the OME infusion [OI] group and 23 in the OME bolus [OB] group) were analyzed. The median percentage of time with an intragastric pH4.0 was higher in the infusion group than in the OB group over 48 h (100% vs 96.6%, P = 0.009) and 72 h (100% vs 87.6%, P = 0.006), and that at an intragastric pH6.0 was higher in the OI group than the OB group over 72 h (97.9% vs 63.5%, P = 0.04). Helicobacter pylori infection was correlated with the fastest increase in intragastric pH, especially in the OI group. In both groups, CYP2C19 genotypes (*1/*1, *1/*17, *17/*17) had no essential effect on intragastric pH.In patients with NVUGIB, OME i.v. bolus followed by continuous infusion is more effective than OME i.v. bolus every 12 h in maintaining higher intragastric pH, regardless of CYP2C19 genetic polymorphisms. H. pylori infection accelerates the initial elevation of intragastric pH.

OBJECTIVES The aim of this study was to assess the functional state of platelets in patients with mild acute pancreatitis and severe acute pancreatitis (S-AP). METHODS The number of platelets and their morphological parameters were measured with Advia 2120. β-Thromboglobulin and platelet factor 4 concentrations were determined by enzyme-linked immunosorbent assay method. To evaluate the expression of platelet glycoproteins, flow cytometry method was used. RESULTS At the time of admission, a multiparameter evaluation of the platelets' function in AP patients showed enhanced platelet activation, which was reflected by an increase in the number of large platelets, concentration of degranulation markers (platelet factor 4 and β-thromboglobulin), expression of glycoprotein (Gp) IIb/IIIa, and decreased mean platelet component. Only in S-AP patients at day 1 a decreased number of platelets and high expression of P-selectin and GpIa were observed, which may suggest their prognostic value. At day 30, the procoagulation state was still present in S-AP patients, because of increased platelets and number of large platelets as well as high GpIIb/IIIa expression. CONCLUSIONS These results may indicate an important role of platelet activation in the pathogenesis of acute pancreatitis and the development of complications in S-AP.

Purpose Determination of the type and frequency of complications developing after diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) as well as the risk factors predisposing to them. Material/Methods The retrospective study, including 734 ERCP performed in 550 patients, with 404 (55%) ES (endoscopic sphincterotomy) during a 4-year period. Results Among 734 ERCP procedures, 76.4% (561) had both diagnostic and therapeutic purpose, 15.2% (112) were only diagnostic. Complications developed after 26 procedures (3.5%): acute pancreatitis (AP) in 8 patients (1.09%), cholangitis in 7 (0.95%) and delayed bleeding in 11 (1.5%) patients. After 49 (6.7%) ES immediate bleeding was observed. The risk factors for AP were: unintentional pancreatic duct contrasting, mechanical lithotripsy, the use of the “pre-cut” technique and bile duct dilatation. Cholangitis was more common in cases with difficult cannulation at older age and with lower baseline bilirubin level. The risk factors for delayed bleeding were: location of the ampulla of Vater in the diverticulum and the use of the “pre-cut” technique. Immediate bleeding was more frequent after revision of bile ducts with Dormia's basket or with balloon, after introduction of contrast medium to the pancreatic duct or in ductal cholelithiasis. Conclusions ERCP performed in the endoscopy unit of a specialist hospital department is a relatively safe procedure, with a low burden of complications as compared to the benefits it provides to appropriately qualified patients.

Ghrelin and leptin are hormones regulating appetite and metabolic processes. Adiponectin plays an important role in the modulation of glucose and lipid metabolism.The objective of the study was to evaluate the levels of plasma ghrelin, leptin, and adiponectin in obese subjects treated with bioenterics intragastric balloon (BIB), low-calorie diet (1500 kcal), and physical exercise.BIB was placed for 6 months in 21 subjects with body mass index 47.3 +/- 5.7. The control group consisted of 15 morbidly obese subjects treated with a low-calorie diet and physical effort. Plasma hormone levels were determined by RIA.In the BIB group, the insertion of the balloon caused a considerable reduction in body mass over a 6-month period (17.1 +/- 8.0 kg) as compared with the control group (3.2 +/- 6.4 kg). After 1 month, the levels of ghrelin increased from 621.9 +/- 182.4 to 903.9 +/- 237 pg/ml and thereafter gradually decreased, reaching the starting level 3 months after the removal of the balloon. In the same group, the levels of leptin decreased from 61.3 +/- 36.7 to 39.9 +/- 17.5 ng/ml. In the control group, the corresponding levels of ghrelin and leptin remained relatively stable. During the observation period, in the BIB group, the levels of adiponectin remained unchanged as opposed to a transient increase noted in the control group.In patients with morbid obesity, weight loss induced by BIB is associated with a decrease in plasma leptin and a transient elevation of plasma ghrelin. It is likely that the changes in hormones regulating the energy balance caused by BIB can prevent an increase in adiponectin level.

Irreversible airflow obstruction may develop in some cases of asthma even in absence of known risk factors such as smoking and environmental insults and despite implementing apparently appropriate therapy. This implies that genetic factors may significantly contribute to determining the severity in the course of the disease. The published reports on genetic predisposition to irreversible bronchoconstriction in asthma, however, are relatively scarce, and disregard its potential association with transforming growth factor (TGF)-beta1 gene polymorphism despite established role that TGF-beta1 plays in airway remodelling. We tested TGF-beta1 single-nucleotide polymorphisms (SNPs) at position +869 of codon 10 (leucine or proline) and position +915 of codon 25 (arginine or proline) for association with irreversible bronchoconstriction in a case-control study involving 110 patients with asthma and 109 controls. Multivariate logistic regression analysis revealed that genotype G/G at codon 25 was significantly associated with irreversible bronchoconstriction in asthmatics (odds ratio = 4.44; 95% confidence interval: 1.00-19.61; P = 0.05), but only after adjustment for gender, disease duration and smoking index. The influence of SNPs at codon 10 on irreversible airway obstruction was not significant. Our results suggest that presence of SNP (+915G/G) at codon 25 in TGF-beta1 gene may predispose to the development of irreversible bronchoconstriction in asthmatic patients, but only when coincident with the male gender, habitual smoking and relevant duration of the disease.

Background Elevated serum concentrations of macrophage-colony stimulating factor (M-CSF) have been found in a variety of malignant diseases. The aim of our study was to assess correlations between serum levels of M-CSF and clinicopathological features and survival rates in patients with colorectal cancer (CRC). Patients/methods M-CSF and the established tumor markers (carcinoembryonic antigen — CEA and carbohydrate antigen — CA 19-9) were investigated in the sera of 116 colorectal cancer patients and correlated with the clinical parameters of the disease and with the survival of patients. We compared M-CSF serum levels in CRC with colorectal adenoma patients. M-CSF was determined using enzyme-linked immunosorbent assay (ELISA). Tumor markers were measured by microparticle enzyme immunoassays (MEIA). Results CRC patients had significantly higher M-CSF and tumor markers levels compared to healthy controls and colorectal adenoma patients, with a significant association between M-CSF levels, disease stage and lymph node metastasis. Serum levels of M-CSF and CEA decreased significantly after radical resection of the tumor. Moreover, the multivariate analysis showed that the serum level of M-CSF in CRC patients was an independent prognostic factor. Conclusion These findings suggest the potential clinical use of circulating M-CSF measurements, particularly in estimating prognosis for patients with CRC.

The purpose of this study was to evaluate the usefulness of serum total sialic acid (SA) for discrimination of malignant and nonmalignant jaundice. Serum SA concentration and its ratio with total protein (SA/TP) were determined in 55 patients with jaundice: 25 malignant and 30 nonmalignant. SA was estimated by enzymatic method. Serum total SA and the ratio SA/TP were significantly higher in malignant than in nonmalignant jaundice. Diagnostic sensitivity of SA and the ratio of SA/TP in both types of jaundice reached the value of 95.8%. The specificity, positive and negative predictive values, and efficiency of SA and SA/TP were higher in malignant than in nonmalignant jaundice. Areas under ROC curves for SA and the ratio of SA/TP in malignant jaundice were higher than in nonmalignant, but there were not statistically significant differences. SA levels and the ratio of SA/TP do not have the ability to discriminate between these types of jaundice.

Gastro-esophageal reflux disease (GERD) may cause chest pain. The aim was to determine the correlation between ischemia and gastro-esophageal reflux in patients with CAD and to assess the influence of short-term "anti-reflux" therapy on the ischemia in patients with GERD and CAD.Fifty patients with angiographically proven CAD underwent simultaneous 24-h continuous ECG and esophageal pH monitoring. We assessed the number of ST-segment depression episodes (ST dep.) and total duration of ischemic episodes, expressed as total ischemic burden (TIB). In pH-metry, we assessed: time percentage of pH lower than 4, total time of pH lower than 4 and the number of pathological refluxes (PR). Patients fulfilling the GERD criteria received a 7-day therapy with omeprazole 20 mg bid. On the 7th day of therapy, simultaneous Holter and esophageal pH monitoring was repeated.Total number of 224 PRs in 42 patients (84%) was recorded during esophageal pH-metry. GERD criteria were fulfilled in 23 patients (46%). Out of 218 episodes of ST dep., 45 (20.6%) correlated with PR. GERD patients had larger TIB and higher number of ST dep. (p0.015 and p0.035, respectively). The anti-reflux therapy reduced all analyzed parameters of esophageal pH monitoring (p0.0022) as well as the number of ST dep. (p0.012) and TIB (p0.05).Gastro-esophageal reflux disease is common in patients with CAD and may provoke myocardial ischemia. Short-term proton pump inhibitors therapy that restores normal esophageal pH significantly reduces myocardial ischemia, possibly due to elimination of acid-derived esophago-cardiac reflex compromising coronary perfusion-the phenomenon known as "linked angina".

Introduction Excessive inflammatory response is one of the major causes of early mortality in acute pancreatitis (AP). Aim To evaluate the serum profiles of E-selectin, interleukin (IL)-6, and IL-10 along with their correlation to the markers of oxidative stress and neutrophil activation in patients with AP and patients with nonpancreatic acute abdominal pain (NPAAP). Methodology This prospective clinical study included 56 patients with AP (28 with mild AP and 28 with severe AP) as well as 15 patients with NPAAP. Results Serum concentrations of E-selectin, IL-10, and IL-6 and plasma concentrations of polymorphonuclear leukocyte elastase (determined on days 1-3, 5, and 10 after admission) were the highest in severe AP during the first 3 days and then declined. At day 10, the E-selectin level in severe AP was still higher than that in mild AP, and the IL-10 concentration increased again. There was no elevation in the E-selectin concentration in NPAAP patients, and IL-10 levels remained unchanged in mild AP. Oxidative stress, measured by serum malondialdehyde and 4-hydroxyalkenals levels, was the most pronounced in severe AP. Conclusions The serum E-selectin concentration is markedly elevated in severe AP and is less in mild AP but not in NPAAP. It may result from stimulation with different inflammatory mediators or indicate vascular endothelium injury mediated by oxidative stress, especially in the severe form of AP.

Cholecystokinin (CCK) acting through its G protein-coupled receptor is now known to activate a variety of intracellular signaling mechanisms and thereby regulate a complex array of cellular functions in pancreatic acinar cells. The best studied mechanism is the coupling through heterotrimeric G proteins of the Gq family to activate a phospholipase C leading to an increase in inositol trisphosphate and release of intracellular Ca2+. This pathway along with protein kinase C activation in response to the increase in diacylglycerol stimulates the secretion of digestive enzymes by the process of exocytosis. CCK also activates signaling pathways in acini more related to other processes. The three mitogen activated protein kinase cascades leading to ERKs, JNKs and p38 MAPK are all activated by CCK. CCK activates the ERK cascade by PKC activation of Raf which in turn activates MEK and ERKs. JNKs are activated by a distinct mechanism which requires higher concentrations of CCK. Both ERKs and JNKs are presumed to regulate gene expression. CCK activation of p38 MAPK also plays a role in regulating the actin cytoskeleton through phosphorylation of the small heat shock protein HSP27. The PI3K-PKB-mTOR pathway is activated by CCK and plays a major role in regulating protein synthesis at the translational level. This includes both activation of p70 S6K leading to phosphorylation of ribosomal protein S6 and the phosphorylation of the binding protein for initiation factor 4E leading to formation of the mRNA cap binding complex. Other signaling pathways activated by CCK receptors include NF-kappaB and a variety of tyrosine kinases. Further work is needed to understand how CCK receptors activate most of the above pathways and to better understand the biological events regulated by these diverse signaling pathways.

Using numerical experiments we show that the phase synchronization concept enables better insight into the synchronization phenomena encountered in coupled nonlinear chaotic circuits. In some cases when the phase plot inspection does not allow to confirm synchrony such kind of behavior can be distinguished by inspection of the phase calculated using the analytic signal approach.

In a group of 193 postinfarction patients with ventricular premature beats on a resting 12-lead ECG, the dispersion of QT and JT intervals was calculated as a difference between maximum and minimum QT and JT intervals in ventricular premature beats. During a follow-up of 38 ± 17 months, death from all causes was noted in 56 patients. Univariate predictors of mortality included QT dispersion ≥100 ms, JT dispersion ≥100 ms, left ventricular ejection fraction 60 years. At multivariate Cox proportional hazards survival analysis, only QT dispersion ≥100 ms, left ventricular ejection fraction 2 = 23.60, p = 0.0000).

We study certain L-series of Rankin-Selberg type associated to Siegel modular forms of degree 2: twists by Dirichlet characters, relation to zeta functions of spinor type, construction of Siegel cusp forms whose Fourier coefficients involve special values of such L-series, etc.

Pancreatic secretagogues that activate digestive enzyme secretion through classic intracellular mediators such as Ca2+ also activate novel signaling kinase cascades. The best defined of these is the MAP kinase cascade, but cholecystokinin also activates jun kinase, p38 MAP kinase, and S6 kinase. These novel pathways are likely involved with pancreatic growth and gene expression.

It was recently found that cholecystokinin (CCK) activates mitogen-activated protein kinases (MAPK) in isolated rat pancreatic acini. The present study evaluates whether one or both types of CCK receptors are capable of MAPK activation in pancreatic AR42J acinar cells as well as CHO cells transfected with CCK-A or CCK-B receptors. CCK significantly increased p44 MAPK and p42 MAPK activities in AR42J cells. Minimal, half-maximal, and maximal responses were observed at 30 and 500 pM and 10 nM, respectively, after CCK-8 stimulation and at 100 pM and 1.5 and 30 nM, respectively, after gastrin stimulation. Glycine-extended gastrin had no effect at 100 nM and a small but significant effect at 1 microM. The CCK-B receptor antagonist L365,260 almost totally blocked MAPK activation in AR42J cells after stimulation with gastrin and glycine-extended gastrin and substantially reduced the activation of both kinases by CCK-8, while the CCK-A receptor antagonist L364,718 was much less effective. The CCK-A-selective agonist A71376, however, was an effective stimulant of MAPK activity. In an alternative approach, stably transfected CHO cells bearing either CCK-A or CCK-B receptors were stimulated with CCK-8. Each receptor induced a time-dependent increase in activity of both MAPKs by five- to sixfold in CCK-A- and CCK-B-bearing cells. In conclusion, both CCK-A and CCK-B receptors activate MAPK in AR42J cells and in transfected CHO cells.

We investigate complex dynamic phenomena in arrays composed of interacting chaotic circuits. Such arrays can be thought of as a model of nonlinear phenomena in spatially extended (high-dimensional or infinite-dimensional) systems and active media with potential applications in brain function modelling and signal processing. In this paper we consider a particular structure of the network in which there exist locally double diffusive interactions between the cells. Such a double interaction can be considered as a paradigm and means for understanding very complex interactions existing in real systems where neighboring cells can communicate in various ways. We consider two basic cases where separate cells without coupling exhibit two different types of chaotic behavior. Depending on the connection structure, initial conditions imposed in the cells the array exhibits various kinds of spatially ordered chaotic waves. Patterns of behavior depending on the excitation of the array and the connection structure are studied in some detail. We present results of simulations showing cooperative phenomena. Depending on the connection structure between the cells and their initial states the array can show spatially ordered patterns of behavior. Such orderly spatial patterns resulting in arrays of chaotic elements are referred to as self-organization. We observed travelling target waves and chaotic wavefronts behaving like autowaves. This kind of autowave-like behavior in arrays of chaotic elements is to our knowledge described for the first time.

This paper presents results of a simulation study of complex dynamic phenomena in arrays composed of interacting chaotic circuits. Such arrays can be thought of as a new paradigm for modelling non-linear phenomena in spatially extended (high-dimensional or infinite-dimensional) systems and active media with potential applications in signal processing. Depending on the connection structure between the cells, the array can show disorganized hyperchaotic behaviour or spatially ordered chaotic waves. Patterns of behaviour depending on the excitation of the array and the connection structure are studied in this paper. Chua circuits are taken as standard chaotic cells.

Background: Clinical and experimental observations indicate that reduced beat-to-beat changes in the cycle length of nonsustained ventricular tachycardia (NSVT) may portend malignant ventricular tachyarrhythmias and sudden cardiac death. The purpose of the study was to test the hypothesis that measures of ventricular rate variability during NSVT (VRV-NSVT) may be useful in identifying patients at high risk of life-threatening arrhythmic events. Methods: The study group consisted of 326 patients who had NSVT on 24-hour ECG recordings. Temporal changes in up to 10 beat-to-beat intervals of NSVT runs (V-V) were assessed. The following parameters of VRV-NSVT were calculated: (1) average value of successive differences in V-V intervals (ADVV); and (2) normalized average value of successive differences in V-V intervals (nADVV). Results: During a mean follow-up of 4 years, 52 (16%) patients had a documented episode of sustained VT or ventricular fibrillation. Patients with these arrhythmic events had significantly (P < 0.001) lower values of ADVV and nADVV variables in comparison to patients without arrhythmic events. The relative risk of malignant arrhythmic events for patients with ADW < 40 ms was 4.9 (P < 0.001), for patients with nADVV < 6%, the risk was 3.9 (P < 0.001). Conclusions: The results of this study indicate a strong and significant relationship between NSVT and the risk of subsequent malignant ventricular tachycardia. The assessment of VRV-NSVT may be useful for identifying patients at high and low risk for subsequent arrhythmic events.

Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were treated with platelet-activating factor receptor (PAF) antagonist—BN 52021 (5 mg/kg) and sacrificed at 1 and 3 h after induction of acute pancreatitis. Malondialdehyde and sulfhydryl groups concentration were measured in pancreatic, lung, and liver tissue as a parameters of oxidant-antioxidant balance. We have shown that BN 52021 exerts only partial protecting effect against Na-TC-induced AP in rats. The positive effects of BN 52021 were expressed by: (1) Significant reduction of hyperamylasemia accompanied by lower malondialdehyde accumulation in pancreatic tissue; (2) Prevention of sulfl hydryl groups depletion in lung tissue; (3) Diminution of necrotic and inflammatory changes in pancreatic tissue; and (4) Improvement of survival rate. We suggest that these effects may depend on the inhibition of PAF-mediated activation and oxidant generation by phagocytes.

Isoxazole‐substituted 1‐aminoethyl‐ and 1‐hydroxyethyiphosphonates were synthesized by a multi‐step procedure and were screened for herbicidal activity against Lepidium sativum L. and Cucumis sativus L. All the synthesized compounds exhibited notable herbicidal activity.

Acute edematous pancreatitis was induced in Wistar male rats by iv infusion of cerulein (CR) in the dose of 5.10(-6)g.kg-1.h-1 during 3 or 6 h. The effect of BN 52021--platelet activating factor (PAF) receptor antagonist, against this model of disease was examined. BN 52021 was applied iv as a bolus injection in the dose of 5.10(-3)g.kg-1 at 0 time. Treatment with this agent significantly ameliorates cerulein-induced acute pancreatitis in rats. The effect of BN 52021 was expressed by significant reduction of pancreas edema, diminution of hyperamylasemia, lack of superoxide dismutase activity depletion, and inhibition of lipid peroxidation in pancreatic tissue. These changes were accompanied by significant reduction of acinar cells vacuolization and remarkable inhibition of infiltration with inflammatory cells in the interacinar space. We suppose that beneficial effect of BN 52021 against cerulein-induced acute pancreatitis in rats depends on the prevention of inflammatory cells activation and subsequent generation of oxygen radicals within pancreatic tissue.

OBJECTIVE We have recently reported that pancreatic growth driven by cholecystokinin released endogenously by feeding the synthetic trypsin inhibitor camostat requires the Ca-activated phosphatase calcineurin. In the present study, we evaluated a number of signal transduction pathways for their activation as part of the growth response and whether their activation was dependent on calcineurin. METHODS Male ICR mice were fed with either chow or chow plus 1 mg/g of camostat. FK506 was administered at 3 mg/kg. After various times from 12 hours to 10 days, pancreatic samples were prepared and assayed for activity of various signal transduction pathway components. RESULTS Camostat feeding increased the activation of extracellular signal-regulated kinases, c-Jun NH2-terminal kinases, and phosphorylation of the translation factor eukaryotic initiation factor 4E and activated the mammalian target of rapamycin pathway that leads to phosphorylation of the ribosomal protein S6 and of the eukaryotic initiation factor 4E binding protein but with different time courses. Treatment of mice with the calcineurin inhibitor FK506 totally blocked c-Jun NH2-terminal kinase activation, partially blocked the mammalian target of rapamycin pathway, and had no effect on extracellular signal-regulated kinase activation or the phosphorylation of eukaryotic initiation factor 4E. CONCLUSIONS The pancreatic growth response is accompanied by activation of a number of signaling pathways regulating transcription and translation, some of which are dependent on and some independent of calcineurin.

Insufficient vascularisation of substitutes in the operative reconstruction of the oesophagus is one of the main causes of the occurrence of anastomotic leaks. In the present study, the blood oxygenation of gastric substitutes for the oesophagus was evaluated before and during the reconstruction. A pulse oximeter was used for the assessment (SJ Medico Teknik AIS, Albertslund, Denmark). Oxygenation in the examined places ranged from 79% to 98%. The values of blood oxygenation in places C1 (fundus of the stomach after the formation of the substitute) and C2 (fundus of the stomach after the formation and stretching of the substitute) were significantly lower than those in analogous places in the stomach before the transformation (C/C1 p0.02; C/C2 p0.03, Fisher test). There were no correlations between pulse oximetry values observed and the presence of anastomosis leak.

Background The day-to-day variability in the number of reflux episodes and symptoms of gastro-esophageal reflux disease is high; therefore, the assessment of reflux disease based on 24-h monitoring may be inaccurate. Aims The aim of the study was to compare prolonged (48 h) and standard (24 h) pH-impedance monitoring (pH-MII). Methods Fifty-four consecutive patients with typical and atypical reflux symptoms underwent 48-h pH-MII. Acid exposure time (AET), total number of reflux episodes (TR), number of symptoms, and symptom association probability (SAP) were analyzed after the first 24 h and compared with the results obtained during 48 h of monitoring. Results The differences between the fractions of patients with normal and abnormal total AET and TR on both days were not significant. The percentage of patients with positive SAP was 57.9 % at 24 h and 71.9 % at 48 h (difference: 14.81 %, 95 % CI 0.7–21.29, P