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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. [ABSTRACT FROM AUTHOR]

Objective To describe the LTPA of older Polish citizens in the nationwide, representative population-based PolSenior Project. Methods A study group comprising 4813 randomly recruited participants aged 65 and over was surveyed. Data concerning LTPA in relation to age, gender, place of residence, and social class have been reported. Results Only 33.6% fulfilled the recommended LTPA criteria. Gardening (64.6%), walking (39.0%) and cycling (37.3%) were the most popular physical activities, followed by gymnastic exercises (18.2%) and dancing (12.8%). Village residents reported walking, gymnastics, swimming, tennis and dancing (32.5%, 9.1%, 1.8%, 0.1%, 8.1%) less frequently than those who live in cities, especially as compared to the residents of the largest cities (45.2%, 28.3%, 13.4%, 1.3%, 15.7%, respectively). However, the frequency of cycling generally decreased with the size of the place of residence. Village residents reported cycling and gardening more frequently (49.2% and 75.8%) than residents of the largest cities (20.6% and 45.8%, respectively). Conclusion There are several differences in the LTPA of older adults in Poland compared with those in North America or Western Europe. Community-based and environmental policies should concentrate on a combination of sustaining existing favorable physical activity (PA) habits (gardening and cycling), and developing access and motivation for participation in LTPA characteristic of developed countries. [ABSTRACT FROM AUTHOR]

Purpose: Considering the important role of neutrophils' activation in the pathogenesis of acute pancreatitis (AP), the aim of our study was to evaluate the expression of leukocytes' adhesion molecules in patients with AP. Patients/methods: Thirty-five patients (16 women and 19 men; age 32-77 years, median 56 years) with AP were prospectively included into our study. The absolute number of leukocytes was estimated by haematologic analyser. Surface neutrophils antigens (CD) were assayed by the direct fluorescence method for whole blood, using a flow cytometer. Results: At the day 1, significant increase of ICAM-1 expression was found in patients with severe AP (S-AP) (7280 mm-3 vs 2850 mm-3 in healthy control; p < 0.05). In the days 2, 3 and 5 it sharply decreased and peaked again to 4860 mm-3 at the day 10. In patients with mild AP (M-AP), not significant elevation of ICAM-1 quickly returned to normal level. In both forms of AP, neutrophil CD62L (L-selectin) expression reached the highest level at the day 1 (8800 mm-3 and 9020 mm-3, respectively in M-AP and S-AP, in comparison to 3400 mm-3 in control; p < 0.05). Expression of CD69 (neutrophils' marker of early activation) significantly increased in both M-AP and S-AP. Conclusions: We have found an early and significant increase of peripheral blood neutrophil CD54/ICAM- 1 expression, specific for S-AP but not for M-AP. It may provide a good marker predicting severe course of pancreatitis. [ABSTRACT FROM AUTHOR]

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 < 0.05). There were ten patients (10/54, 18.5 %) with positive SAP after 48 h that had been negative in the first 24 h. In comparison to 24 h monitoring, patients reported a significantly increased number of various symptoms correlated with reflux after 48 h. Conclusions: Extending pH-MII monitoring to 48 h does not improve the detection of abnormal acid exposure. However, it does increase the fraction of patients with positive symptom-reflux association by as much as 18.5 %. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Compares the value of linearly and nonlinearly corrected QT intervals for identifying high-risk patients. Effect of more accurate adjustment of the QT interval for heart rate on the prognostic significance of the corrected QT interval in patients with remote myocardial infarction; Sensitivity and predictive accuracy of corrected QT interval variables.

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 <40%, complete bundle branch block, ‘R-on-T’ index of ventricular premature beats <1 and age of patients >60 years. At multivariate Cox proportional hazards survival analysis, only QT dispersion ≥100 ms, left ventricular ejection fraction <40% and complete bundle branch block had an independent relation to postinfarction mortality. The final model selected increased QT dispersion as the prognostic factor which was the most strongly related to mortality (χ[sup 2] = 23.60, p = 0.0000). [ABSTRACT FROM AUTHOR]

Compares the effects of cholecystokinin (CCK) and epidermal growth factor (EGF) on the activation of components of regulated kinases (ERK) pathways, including mitogen-activated protein kinases (MAPK). Methodology used to conduct the study; Effect if EGF and CCK on the activity of MAPK in rat pancreatic acini; Conclusion of the study.

Examines whether cholecystokinin (CCK) activates 90-kDa ribososmal S6 protein kinase (p90rsk) in pancreatic acini, as well as the intracellular signaling pathways responsible for this activation. Identification of p90rsk in pancreatic acini by immunoprecipitation and Western blotting; Effects of specific inhibitors of different pathways in p90rsk.

Investigates the effect of activating the Gq protein-coupled cholecystokinin (CCK) receptor on different signaling molecules in the mitogen-activated protein kinase (MAPK) cascade in pancreatic acinar cells. Effect of epidermal growth factor (EGF) and CCK on MAPK activity; Activation of MAPK kinases MEK1 and MEK2 by EGF and CCK.

Examines whether cholecystokinin (CCK) activates S6 protein kinase (p90rsk) in pancreatic acini, as well as the intracellular signaling pathways responsible for the activation. Threshold concentration of CCK; Treatment of acini with ionomycin; Regulation of protein phosphorylation in the cytoplasm.

In a group of 191 postinfarction patients, the low variability of cycle lengths in nonsustained ventricular tachycardia was associated with poor prognosis during follow-up. By use of Cox model analysis it was found that reduced ventricular rate variability was a powerful independent predictor of sudden death and all-cause mortality in this group of patients. [ABSTRACT FROM AUTHOR]

There is a growing body of evidence for a prothrombotic tendency in patients with primary biliary cholangitis (PBC). The aim of the study was to evaluate coagulation disorders in patients with early stage PBC compared to healthy controls and evaluation of their relationship with clinical data, with particular emphasis on minimal hepatic encephalopathy (MHE). Fifty-one participants (PBC group – 38 patients, all patients but one Child-Pugh A; control group – 13 healthy controls) were included in our prospective, single center study. We assessed the plasma levels of sGPV, plasma procoagulant phospholipids (PPL) and rotational thromboelastometry (ROTEM) profiles in all study participants. Porto-systemic encephalopathy syndrome test was used to assess MHE. The sGPV levels were higher in the PBC group compared to the controls: 36.07 ​± ​11.32 ​ng/mL vs 27.04 ​± ​11.72 ​ng/mL, p ​= ​0.031. The PPL level was lower in the PBC group compared to controls resulting in increased clotting time in a factor Xa-based coagulation assay: 54.65 (47.83–58.83) sec. vs 45.90 (43.3–50.5) sec., p ​= ​0.0065. PPL levels were correlated with platelet count (rho ​= ​−0.46, p ​= ​0.001). ROTEM parameters did not differ significantly between groups. Coagulation parameters did not differ significantly between patients with and without MHE. We have showed increased levels of sGPV - a plasma marker of platelet activation by thrombin in patients with early stage PBC compared to healthy controls. We found no relationship between the coagulation disorders and the occurrence of MHE. The PPL level was lower in the PBC group. [ABSTRACT FROM AUTHOR]

Background/Aims: Intestinal metaplasia (IM) of the stomach is a precancerous condition that is often not visible during conventional endoscopy. Hence, we evaluated the utility of magnification endoscopy and methylene blue (MB) chromoendoscopy to detect IM. Methods: We estimated the percentage of gastric mucosa surface staining with MB, mucosal pit pattern, and vessel visibility and correlated it with the presence of IM and the percentage of metaplastic cells in histology, similar to the Operative Link on Gastric Intestinal Metaplasia (OLGIM) stage. Results: IM was found in 25 of 33 (75.8%) patients and in 61 of 135 biopsies (45.2%). IM correlated with positive MB staining (p<0.001) and other than dot pit patterns (p=0.015). MB staining indicated IM with better accuracy than the pit pattern or vessel evaluation (71.7% vs. 60.5% and 49.6%, respectively). At a cut-off point of 16.5% for the MB-stained gastric surface, the sensitivity, specificity, and accuracy of chromoendoscopy in the detection of advanced OLGIM stages were 88.9%, 91.7%, and 90.9%, respectively. The percentage of metaplastic cells detected on histology was the strongest predictor of positive MB staining. Conclusions: MB chromoendoscopy can serve as a screening method for detecting advanced OLGIM stages. MB mainly stains IM areas with a high concentration of metaplastic cells. [ABSTRACT FROM AUTHOR]

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)-β1 gene polymorphism despite established role that TGF-β1 plays in airway remodelling. We tested TGF-β1 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-β1 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. [ABSTRACT FROM AUTHOR]

Minimal hepatic encephalopathy (MHE) is an important complication of chronic liver disease (CLD); however, MHE burden in patients with primary biliary cholangitis (PBC) has not been determined yet. Therefore, our study aimed to assess the prevalence of MHE in a typical cohort of middle-aged, patients with PBC suspicion of liver fibrosis and to investigate the relationship between MHE, basic laboratory tests and the stage of liver fibrosis. Fifty-one patients (38 with PBC and 13 controls), were prospectively enrolled. Portosystemic Encephalopathy-Syndrome test was used to diagnose MHE. Elastography point qualification (ElastPQ) and non-invasive markers (APRI and FIB-4) were used to assess liver fibrosis. The severity of CLD was assessed using the Model of End-Stage Liver Disease (MELD) and Child-Pugh score. MHE was diagnosed in 9 patients (24.3%) with PBC and none in the control group. As many as 44.4% of the patients with MHE had neither advanced fibrosis nor cirrhosis, as demonstrated using non-invasive markers of liver fibrosis or ElastPQ. The MELD score was the only predictor of MHE with cut-off value 8.5 [AUC ​= ​0.753, CI 95% ​= ​0.569 to 0.938)] with sensitivity of 56%, specificity of 85% and accuracy of the test of 78%. Non-invasive markers of liver fibrosis and ElastPQ did not predict MHE. MHE may occur in PBC despite no evidence of advanced liver fibrosis or cirrhosis. The slightly elevated MELD score may indicate a substantially increased risk of MHE in patients with PBC. [ABSTRACT FROM AUTHOR]

Background: Endoscopic techniques have become the first-line therapy in bariatric surgery-related complications such as leaks and fistulas. We performed a systematic review and meta-analysis on the effectiveness of self-expandable stents, clipping, and tissue sealants in closing of post-bariatric surgery leak/fistula. Methods: A systematic literature search of the Medline/Scopus databases was performed to identify full-text articles published up to February 2019 on the use of self-expandable stents, clipping, or tissue sealants as primary endoscopic strategies used for leak/fistula closure. Meta-analysis of studies reporting stents was performed with the PRISMA guidelines. Results: Data concerning the efficacy of self-expanding stents in the treatment of leaks/fistulas after bariatric surgery were extracted from 40 studies (493 patients). The overall proportion of successful leak/fistula closure was 92% (95% CI, 90–95%). The overall proportion of stent migration was 23% (95% CI, 19–28%). Seventeen papers (98 patients) reported the use of clipping: the over-the-scope clips (OTSC) system was used in 85 patients with a successful closure rate of 67.1% and a few complications (migration, stenosis, tear). The successful fistula/leak closure using other than OTSC types was achieved in 69.2% of patients. In 10 case series (63 patients), fibrin glue alone was used with a 92.8–100% success rate of fistula closure that usually required repeated sessions at scheduled intervals. The complications of fibrin glue applications were reported in only one study and included pain and fever in 12.5% of patients. Conclusions: Endoscopic techniques are effective for management of post-bariatric leaks and fistulas in properly selected patients. [ABSTRACT FROM AUTHOR]

We aimed to assess the relationship between procoagulant imbalance and the occurrence of variceal bleeding in patients with liver cirrhosis. 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. 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). 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. • Procoagulant imbalance can be easily detected in liver cirrhosis. • The hypercoagulability in liver cirrhosis does not prevent variceal bleeding. • ROTEM shows no association between variceal bleeding and coagulopathy in cirrhosis. [ABSTRACT FROM AUTHOR]

Objective: The study aimed at assessing the effect of thrombocytopenia and platelet function abnormalities on the occurrence of variceal bleeding in patients with cirrhosis. Methods: The results of impedance aggregometry, von Willebrand factor antigen level and thromboelastometry (TEM) with and without the addition of a platelet inhibitor (FIBTEM®, EXTEM® test, respectively) were compared in two patient groups: Group 1 (n = 32) – patients with moderate or large esophageal or gastric varices, who had never had symptoms of acute gastrointestinal bleeding and Group 2 (n = 26) – patients with history of variceal bleeding. Results: Standard clotting test indicated more hypocoagulable profile in Group 2 compared to Group 1. However, no differences in any TEM component were observed between groups in EXTEM® test. The contribution of platelets to clot strength was significantly higher in Group 2 than in Group 1 [PLT% = 74.2 (67.5–80.4) versus 68.8 (63.7–76.5) %; p =.039]. The aggregation index was also higher in Group 2 compared to Group 1, although not statistically significant [% of healthy = 96.9 (73.2–140.1) versus 67.6 (52.5–118.8) %, p =.195]. No differences in vWF antigen levels were observed between groups. Conclusions: The results of thromboelastometry and aggregometry indicate increased contribution of platelets in clot formation in patients with a history of variceal bleeding compared to cirrhotic patients who never bled. Comparable effectiveness of hemostasis in both groups is most likely associated with the compensatory role of platelets. Increased platelet activity in this group of patients is probably due to a mechanism independent of the von Willebrand factor antigen level. [ABSTRACT FROM AUTHOR]

Highlights • Cirrhotics with esophageal varices have an imbalance of IL-18 and TGF-β1 levels. • Peripheral IL-18 and TGF-β1 levels correlate with liver failure indicators. • Peripheral Il-18 levels decrease with beta-blocker therapy. • Peripheral IL-18 levels can be a marker of clinically significant portal hypertension. Abstract Introduction The presence of esophageal varices in liver cirrhosis indicates clinically significant portal hypertension (PH), that results from structural and dynamic changes in the liver and systemic circulation including the activation of several fibrotic and inflammatory pathways. We assessed if interleukin-18 (IL-18) and transforming growth factor-β1 (TGF-β1) serum levels can be used as PH markers and reflect its severity. Material and methods IL-18 and TGF-β1 peripheral blood levels were analyzed in 83 cirrhotic patients with esophageal varices compared to healthy individuals, in relation to MELD and Child-Pugh scores, laboratory and Doppler ultrasound parameters, and non-selective beta-blocker therapy (NSBB). Results IL-18 concentration was significantly higher in cirrhotic patients, while TGF-β1 concentration was lower than in controls. MELD score correlated positively with IL-18 levels and negatively with TGF-β1 levels. IL-18 levels correlated positively with bilirubin, INR, ALT and AST levels, and negatively with albumin levels and erythrocyte count. TGF-β1 levels correlated positively with platelet count, leukocyte, and erythrocyte count, and negatively with bilirubin levels and prothrombin time. Moreover, significant correlations were found: between IL and 18 levels and portal, mesenteric superior, and splenic vein velocity, and between TGF-β1 levels and splenic vein diameter and spleen size. In a subgroup of patients, IL-18 levels significantly decreased after NSBB. Conclusion The observed imbalance of peripheral IL-18 and TGF-β1 levels indicates clinically significant PH associated with the presence of esophageal varices in cirrhosis. The correlation of IL-18 levels with liver failure indicators and decrease with NSBB suggest an important role of IL-18 in disease progression and its potential use as noninvasive test for PH assessment. [ABSTRACT FROM AUTHOR]

Acoustocerebrography is a novel, non-invasive, transcranial ultrasonic diagnostic method based on the transmission of multispectral ultrasound signals propagating through the brain tissue. Dedicated signal processing enables the estimation of absorption coefficient, frequency-dependent attenuation, speed of sound and tissue elasticity. Hypertension and atrial fibrillation are well known factors correlated with white matter lesions, intracerebral hemorrhage and cryptogenic stroke numbers. The aim of this study was to compare the acoustocerebrography signal in the brains of asymptomatic atrial fibrillation patients with and without hypertension. The study included 97 asymptomatic patients (40 female and 57 male, age 66.26 ± 6.54 years) who were clinically monitored for atrial fibrillation. The patients were divided into two groups: group I (patients with hypertension) n = 75, and group II (patients without hypertension) n = 22. Phase and amplitude of all spectral components for the received signals from the brain path were extracted and compared to the phase and amplitude of the transmitted pulse. Next, the time of flight and the attenuation of each frequency component were calculated. Additionally, a fast Fourier transformation was performed and its features were extracted. After introducing a machine learning technique, the ROC plot of differentiations between group I and group II with an AUC of 0.958 (sensitivity 0.99 and specificity 0.968) was obtained. It can be assumed that the significant difference in the acoustocerebrography signals in patients with hypertension is due to changes in the brain tissue, and it allows for the differentiating of high-risk patients with asymptomatic atrial fibrillation and hypertension. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and aim Antibiotics have many beneficial effects but their uncontrolled use may lead to increased risk of serious diseases in the future. Our hypothesis is that an early antibiotic exposition may affect immune system by altering gut microbiota. Therefore, the aim of the study was to determine the effect of penicillin treatment on gut microorganisms and immune system of mice. Methods 21-days old C57BL6/J/cmdb male mice were treated with low-dose of penicillin (study group) or water only (control group) for 4 weeks. Tissue and stool samples for histology or microbiome assessment and peripheral blood for CBC and flow cytometry evaluation were collected. Results We found high variability in microbiota composition at different taxonomic levels between littermate mice kept in the same conditions, independently of treatment regimen. Interestingly, low-dose of penicillin caused significant increase of Parabacteroides goldsteinii in stool and in colon tissue in comparison to control group (9.5% vs. 4.9%, p = 0.008 and 10.7% vs. 6.1%, p = 0.008, respectively). Moreover, mice treated with penicillin demonstrated significantly elevated percentage of B cells (median 10.5% vs 8.0%, p = 0.01) and decrease in the percentage of total CD4 + cell (median 75.4% vs 82.5%, p = 0.0039) with subsequent changes among subsets - increased percentage of regulatory T cells (Treg), T helper 1 (Th1) and T helper 2 (Th2) cells. Conclusion Our study showed significant effect of penicillin on B and T cells in peripheral blood of young mice. This effect may be mediated through changes in gut microbiota represented by the expansion of Parabacteroides goldsteinii. [ABSTRACT FROM AUTHOR]

Recent studies report an increased risk of enteric infections in patients treated with proton pump inhibitors (PPIs). Polymorphonuclear neutrophils (PMNs) play a key role in host response to bacterial infection. We evaluated the effect of omeprazole and pantoprazole treatment on the PMN function. Fifteen patients were treated with omeprazole 20 mg daily and 15 patients with pantoprazole 40 mg daily for 7 days. Treatment with omeprazole or pantoprazole had no effect on spontaneous nitroblue tetrazolium (NBT) test results. Significant increase in the percentage of phagocytes in the omeprazole group in stimulated NBT test (by 69%) was found. Treatment with omeprazole or pantoprazole had no effect on nitric oxide (NO) concentration in the PMN culture supernatant and serum, cyclic guanosine monophosphate concentration in the PMN culture supernatant and serum, as well as inducible nitric oxide synthase (iNOS) protein expression and p38 mitogen-activated protein kinase activity in PMNs. In conclusion, treatment with PPI has no effect on NO production and p38 mitogen-activated protein kinase activity in PMNs. Interestingly, short-term treatment with omeprazole but not with pantoprazole enhances PMN reactive oxygen species production. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Peptic ulcer remains the most frequent cause of upper gastrointestinal bleeding. Treatment of bleeding with simultaneous combination of two endoscopic techniques has proved to be more efficient than monotherapy. None of the published comparative studies of various contact coagulation modalities have confirmed the superiority of one of these techniques over the others. Aim: To compare the therapeutic outcomes of the use of a device enabling both injection of adrenaline solution and bipolar electrocoagulation (A + BE) to those of combined adrenaline injection with mechanical therapy (haemostatic clips) (A + HC) in the treatment of peptic ulcer bleeding. Material and methods: Fifty-two subjects with bleeding ulcers were assigned to the A + BE group, and 55 patients were treated with A + HC. Results: Overall, treatment failed in 20 patients (20/107, 18.7%): in 10 individuals from the A + BE group (10/52; 18.2%) and in 10 individuals from the A + HC group (10/55; 19.2%) (p > 0.05). Primary haemostasis was not obtained in 7 patients (6.5%): in 4 patients in the A + BE group and in 3 patients in the A + HC group (p > 0.05). Ten individuals (9.3%) experienced recurrent bleeding during hospitalisation: 4 patients from the A + BE group and 6 patients from the A + HC group (p > 0.05). Finally, in 96.3% of the patients (n = 103) the endoscopic treatment proved efficient with regards to obtaining haemostasis during hospitalisation. Surgical intervention was required in 4 individuals (3.7%): 2 patients in the A + BE group and 2 patients treated with A + HC (p > 0.05). Three patients (2.8%) - all from the A + HC group - died during hospitalisation. No significant intergroup differences were documented with regards to the mean number of transfused blood units and the mean length of hospital stay. Conclusions: The efficacy of combined endoscopic treatment of ulcer bleeding with a probe enabling simultaneous bipolar electrocoagulation and adrenaline injection seems comparable to the widely used dual technique of adrenaline injection and haemostatic clipping. [ABSTRACT FROM AUTHOR]

The aim of the study was to present the classification of anatomical variations of the stomach, based on the radiological and historical data. In years 2006-2010, 2,034 examinations of the upper digestive tract were performed. Normal stomach anatomy or different variations of the organ shape and/or topography without any organic radiologically detectable gastric lesions were revealed in 568 and 821 cases, respectively. Five primary groups were established: abnormal position along longitudinal (I) and horizontal axis (II), as well as abnormal shape (III) and stomach connections (IV) or mixed forms (V). The first group contains abnormalities most commonly observed among examined patients such as stomach rotation and translocation to the chest cavity, including sliding, paraesophageal, mixed-form and upside-down hiatal diaphragmatic hernias, as well as short esophagus, and the other diaphragmatic hernias, that were not found in the evaluated population. The second group includes the stomach cascade. The third and fourth groups comprise developmental variations and organ malformations that were not observed in evaluated patients. The last group (V) encloses mixed forms that connect two or more previous variations. [ABSTRACT FROM AUTHOR]

Abstract: Abstract: Both descriptive and longitudinal studies of aging are nowadays a subject of growing interest in different countries worldwide. However, in Poland and other Central–Eastern European countries, such comprehensive, nationally representative, multidimensional studies were never performed in the past in elderly population. The present paper describes the PolSenior project including its objectives, sample selection and structure, methods, fieldwork procedures and study flow. The aim of the project was to examine medical, psychological and socioeconomic aspects of aging in Poland. The research sample included 5695 respondents (2899 males and 2796 females) split into six equally sized age groups of elderly individuals (65–69 years, 70–74 years, 75–79 years, 80–84 years, 85–89years, 90+years) and one group of subjects just about to enter old age (55-59 years). Subjects were recruited using three stage stratified, proportional draw. The response rate was 42% and ranged from 32% to 61% between provinces. The study consisted of three visits performed by trained nurses including questionnaire survey, comprehensive geriatric assessment and blood and urine sampling. The questionnaire consisted of medical and specific socioeconomic questions. The comprehensive geriatric assessment included blood pressure and anthropometric measurements, as well as selected scales and tests routinely used in the examination of elderly subjects. Blood and urine samples were collected from 4737 and 4526 individuals, respectively. More than 50 biochemical parameters were measured, and DNA was isolated and banked. In a selected group of 1018 subjects, a medical examination by a physician was performed. The self-rated health was lower in females than in males in age groups 70–84, but similar in individuals of both sexes aged 65-69 and  85 years. Besides providing data on health and functioning of elderly population, the PolSenior project aims to analyze interrelationships between different elements of health and social status, and between genetics and health status in advanced age. The results of the PolSenior project will facilitate prioritizing the state''s public health and social policies in elderly population. Such a program provides also an excellent starting point for longitudinal studies and a basis for comparative analysis between Poland and other European countries or regions. [Copyright &y& Elsevier]

Background: Specialized intestinal metaplasia (SIM) in Barrett's esophagus is a risk factor of esophageal adenocarcinoma. It often occurs focally and cannot be distinguished from surrounding columnar epithelium with conventional endoscopy.Aims: The purpose of this study was evaluation of methylene blue (MB) staining and magnification endoscopy with comparison of pit-pattern classifications according to Endo and Guelrud, in detection of SIM in Barrett's esophagus.Methods: Twenty-five patients, aged 33-77 years (average 57 years), with displacement of Z line were prospectively enrolled and underwent gastroscopy with the use of magnification up to 115 times (Olympus GIF Q160Z). Biopsy for histopathologic examination was taken from sites stained with MB and/or places with particular pit patterns. A control group consisted of ten patients with normal gastro-esophageal junction.Results: SIM was proved in nine patients, and significantly more frequently in patients with hiatal hernia and Barrett's segment longer than 3 cm. Round or thin linear pit patterns according to Guelrud's and small round and straight pit patterns according to Endo's classification were coupled with columnar epithelium. SIM was associated with deep linear and foveolar pit patterns in Guelrud's classification. Other pit patterns were less characteristic. Both classifications had high sensitivity (Endo's 85.7%, Guelrud's 92.8%) but poor specificity (respectively, 21.15 and 28.4%) in detection of SIM. Sensitivity and specificity of MB staining were, respectively, 71.4 and 40.6%.Conclusions: Despite existing association between mucosal surface structure and histology, we find no convincing data indicating that pit-pattern evaluation may replace multiple biopsies taken according to recommendations from Seattle for detection of SIM in Barrett's esophagus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 G[sub q] family to activate a phospholipase C leading to an increase in inositot trisphosphate and release of intracellular Ca[sup 2+]. 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 whish 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 phosphorytation 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-κB 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. [ABSTRACT FROM AUTHOR]