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Liver fibrosis is a chronic and complex pathological process, occuring in patients with chronic liver diseases. The most common cause of liver fibrosis is the alcoholic liver disease, viral hepatitis type B, C and D, as well as autoimmune diseases. Other causes include metabolic dysfunctions like hemachromatosis and Wilson’s disease, biliary duct disorders, damaging effects of medicine and parasite infections. Fibrosis’ dynamics and progres speed depend on the nature of underlying mechanisms and are characterized by accumulation of ECM elements. They vary from patient to patient and are directly correlated to aberrations of homeostasis degradation and production of liver connective tissue. In liver fibrosis the main source of ECM are hepatic stellate cells (HSCS), although other cells are also able to produce ECM such as: portal fibroblasts, narrow-derived cells, biliary duct epithelial cells and epithelial mesenchymal transition hepatocytes. The HSCS activity is stimulated by proinflammatory cytokines, oxidative and nitrosative stress which lead to different pathologies such as: inflammation, steatosis, fibrosis, cirrhosis, liver-cell cancer. Alcohol, the main fibrotic agents is metabolized almost entirely in the liver, so the organ is extremely sensitive to its negative intermediate and mediate influence. Factors influencing alcoholic liver failure are not only oxidative and nitrosative stress and proinflammatory cytokines activity, but also reductive stress, hepatocytes; hypoxia, mucous membranę dysfunction and intestine flora influence, as well as genetic and immunological factors. Though in last several yers there has been a great advancement in our knowledge of liver fibrosis mechanisms, it remains tough to diagnose the proces in its early stages and consequently apply an efficient therapy. The challenge for the futur is finding useful biomarkers and new therapeutic goals.

In recent years, impressive advances in the knowledge about a vast number of microbes living in the human body and interactions between the microbiota and the human body have been observed. All micro-organisms that live in the human body consist of around 10 ^ 14 cells. The number of microbial cells colonizing the human body is ten times higher than the number of its own cells and the weight of all micro-organisms is about 2-2.5 kg. The number of bacterial genes is 50-100 times greater than the number of genes in the human body. Nowadays, the human microbiota is often regarded as a “newly discovered organ” or even as a “supergenome”. The results of many studies have revealed that disruption of the bowel microecosystem may affect the development of irritable bowel syndrome (IBS) symptoms. Therefore, manipulation of the gut microflora was hoped to be a new tool in the treatment of this disease. Various methods (probiotics, prebiotics, antibiotic therapy, transplantation of faecal flora) have been used to modify the intestinal microbiota by supporting the expansion of bacteria considered beneficial and reducing the number of those regarded as harmful, thus alleviating the IBS symptoms. There is much evidence in the literature to suggest that the intestinal microbiota and the gut-intestinal axis are important factors in the pathogenesis of IBS. Moreover, the literature findings have demonstrated beneficial effects of modifying the intestinal flora composition in alleviating IBS symptoms. Although the pathophysiology of IBS and the role of the intestinal microflora and gut-intestinal axis in it are well known, many issues are still to be elucidated. Further research into the bacteria identified in stool and colon mucosa of healthy individuals should provide more information on restoration of intestinal homeostasis in IBS patients.

INTRODUCTION AND OBJECTIVE Screening colonoscopy is a recommended tool, and the most sensitive and cost-effective method for reducing the incidence of colorectal cancer (CRC). OBJECTIVE The purpose of the study was to present the results of a 5-year screening for early detection of CRC carried out among the population of the central-eastern regions of Poland, primarily in Lublin Province. MATERIALS AND METHOD Screening colonoscopy was conducted in a group of 1,009 patients - 636 women and 373 men, aged 40-65 years. RESULTS Neoplastic polyps were found in 275 patients, advanced adenomas in 49 patients and adenocarcinoma in 13. 70.55% of neoplastic polyps was located in the distal colon, 18.9% in the proximal part and 10.55% in both regions, advanced adenomas in 79.59%, 8.16% and 12.25%, respectively. Adenocarcinoma was located in the proximal colon in 2 cases and in the distal region in 11 cases. Neoplastic polyps and advanced adenomas occurred significantly more frequently in smokers than in non-smokers. Neoplastic polyps were found statistically more frequent in males than in females, among the overweight and obese patients, than in subjects with normal BMI, and more frequently in the group of urban, compared to rural patients. However, the frequency of advanced adenomas and CRC was not statistically different in those groups. The incidence of CRC was statistically more frequent in males than in females. Smoking and male gender were significant risk factors for developing neoplastic polyps. Male gender seemed to predispose to CRC. Obesity was found to favour advanced adenomas. CONCLUSIONS The results of screening found neoplastic polyps in every third person (mean) who did not have any symptoms suggestive of colon pathology. Advanced adenomas were found in 5% of the examined and CRC was detected in 1.29% of participants. Smoking, male gender and overweight were significant risk factors for developing neoplastic polyps. No correlation was found between gender and the location of neoplastic polyps and advanced adenomas in the colon.

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn disease (CD). Similar symptoms, but different treatment procedures for both diseases require precise diagnosis. MicroRNAs (miRNAs) are major posttranscriptional players that regulate the expression of genes during the inflammation and thus could be appropriate biomarkers for differentiation between UC and CD. For this purpose, we analyzed the expression of miR-21-3p, miR-31-3p, miR-125b-1-3p, miR-146a-3p, miR-155-5p, and E-cadherin (CDH1) genes associated with IBD, in 67 tissue samples: 28 inflamed mucosa samples (n=16 UC, n=12 CD), 28 adjacent normal colonic mucosa (n=16 UC, n=12 CD), and 11 normal mucosa from healthy patients using reverse transcription real-time RT-PCR. We found all analyzed miRNAs were significantly overexpressed in UC tissue as compared to adjacent normal tissue of patients with UC, as well as to normal mucosa from healthy controls. Four miRNAs (except miR-125b-1-3p) were significantly upregulated in CD lesions as compared to adjacent normal tissue of patients with CD, and four miRNAs, except miR-146a-3p, were significantly higher in CD samples compared to normal mucosa from healthy individuals. In the CD group, we found an inverse correlation between miR-155-5p or miR-146a-3p expressions and CDH1expression in inflamed mucosa. This type of correlation was also detected for miR-213p in adjacent normal tissue and CDH1 in inflamed mucosa, as well as between miR-155-5p and CDH1 in adjacent normal tissue. Elevated miRNA expression is characteristic for IBD-mediated inflammation process and inversely correlated with CDH1 gene expression, which suggest involvement of epithelial to mesenchymal transition (EMT) in IBD development.

Background Interaction between TL1A and death receptor 3 (DR3) is associated with the pathogenesis of inflammatory bowel disease (IBD), although their role in the development of this disease remains not fully explained. Some studies showed elevated expression of TL1A and DR3 in inflamed intestinal tissue but currently there are no reports concerning expression of DR3 on peripheral blood mononuclear cells (PBMCs) of IBD patients which was the subject of our study. Methods We performed flow cytometry analysis of DR3 expression on CD4(+), CD8(+), CD11c(+), CD14(+) or CD20(+) PBMCs of adults and children with IBD and healthy volunteers with respect to C-reactive protein (CRP) levels in blood. Blood samples were collected from pediatric patients before the beginning of therapy, whereas adults patients were undergoing anti-inflammatory IBD treatment and had much lower CRP levels. Results With regard to appropriate healthy volunteers, children with IBD had elevated percentage of DR3-expressing CD4(+), CD8(+), CD11c(+) and CD20(+) PBMCs which, with the exception of DR3(+) CD11c(+) cells in children with ulcerative colitis, was correlated with CRP level in blood. Adult patients had increased frequency of DR3(+) CD8(+) and CD20(+) PBMCs and their CRP levels correlated only with DR3(+) CD8(+) cells. Conclusions In comparison to healthy volunteers, untreated children with IBD have higher percentage of DR3(+) PBMCs than adults with IBD undergoing anti-inflammatory treatment. In most of the investigated PBMCs populations, the frequency of DR3(+) cells is correlated with the level of CRP. We suggest anti-inflammatory treatment may lead to reduction in the frequency of DR3(+) PBMCs. © 2016 International Clinical Cytometry Society

Interaction between TL1A and death receptor 3 (DR3) co-stimulates T cells, induces production of several pro-inflammatory cytokines and has been linked to pathogenesis of inflammatory bowel disease (IBD). This study aimed to establish a link between expression of TL1A and selected TL1A-induced pro-inflammatory cytokines involved in IBD pathogenesis (IL-4, IL-13, IL-17A and IFN-γ) and to investigate a connection between serum concentration of TL1A in patients with IBD and activation of peripheral blood T cells. Elevated levels of IL-4 (2.91-fold) and IL-13 (4.05-fold) mRNA were detected in the inflamed colon mucosa of patients with ulcerative colitis (UC), IFN-γ mRNA was upregulated (3.23-fold) in the inflamed colon mucosa of patients with Crohn's disease (CD), whereas upregulation of IL-17A and TL1A mRNA was present in the inflamed colon mucosa of patients with both CD and UC (IL-17A: 4.48-fold and 2.74-fold, TL1A: 3.19-fold and 3.22-fold, respectively) vs. control subjects. We did not detect any changes in DR3 mRNA expression in the investigated groups of patients. TL1A mRNA level in colon mucosa of patients with IBD correlated only with the level of IL-17A mRNA but no other investigated cytokines. In colon mucosa, expression of TL1A and DR3 was localized to enterocytes and lamina propria mononuclear cells. We did not find any correlation between serum concentrations of TL1A and IL-17A or changes of CD4(+) or CD8(+) lymphocytes phenotype in patients with IBD. Therefore, our data indicate that TL1A may contribute to pathogenesis of IBD via local but not systemic induction of IL-17A but not IL-4, IL-13 or IFN-γ.

Summary Aim. The aim of the present study was to analyse the impact of education of patients with irritable bowel syndrome (IBS) on their quality of life. Methods. The study was carried out at the Gastroenterology Outpatient Clinic of the Independent Public Clinical Hospital No. 4 in Lublin and Gastroenterology Outpatient Clinic of the Cardinal Stefan Wyszynski Regional Specialist Hospital in Lublin in the years 2010–2011. The quality of life was analysed using the Quality of Life Questionnaire (QOL-Q R. Schalock, K. Keith). Material. The group of 83 patients with the diagnosis of irritable bowel syndrome, who gave their consent for inclusion in the study, was provided with information about the essence of the disease, disease-related diet and lifestyle, course of the disease, medications, and check-ups. Results. Our patients educated by the physician, nurse and those provided with written information had substantially higher scores in multi-dimensional aspects of the quality of life after education. Six months after education patients with IBS showed a significantly higher quality of life in all aspects, i.e. Satisfaction, Competence/productivity, Empowerment/ independence and Social inclusion/community integration. The understanding of the essence of their disease contributed to a decrease in anxiety associated with the neoplastic disease and worrying symptoms, which significantly reduced the incidence of complaints. Conclusions. 1. Quality of life of patients with irritable bowel syndrome is substantially reduced in all the examined spheres. 2. Education of patients with IBS resulted in enhanced quality of life and reduced disease-related complaints. 3. Education of patients with IBS plays a significant role in the entire therapeutic process.

There are some divergent data concerning the role of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of MMP (TIMP)-2 in the pathogenesis of alcoholic cirrhosis (AC) and chronic pancreatitis (CP). Our objective was to evaluate the activity of MMP-2, MMP-9 and TIMP-2 serum levels in patients with AC and CP. Twenty-one patients with diagnosis of AC and twenty-two with CP admitted to the outpatient clinic for a control visit were enrolled. All results were compared with age and sex-matched control group (n=19). The sera obtained from venous blood were stored at -70°C for further analysis. Activity of MMP-2 and MMP-9 were evaluated with gelatin zymography, TIMP-2 serum level was analyzed with the usage of ELISA method. A significant decrease of serum MMP-2 activity was noted in sera of AC and CP patients in comparison with control. Activity of MMP-9 was elevated only in CP patients and TIMP-2 serum level was elevated only in AC patients. Decreased activity of MMP-2 in AC patients can contribute to cirrhosis development. The high level of MMP-9 in serum related to CP patients theoretically can exacerbate the inflammatory process within the pancreas.

Background Liver cirrhosis is associated with functional abnormalities of the cardiovascular system with co-existing electrocardiographic (ECG) abnormalities. Objectives The aim was to analyze ECG changes in patients with cirrhosis, to evaluate whether alcoholic etiology of cirrhosis and ascites has an impact on ECG changes. Material and methods The study involved 81 patients with previously untreated alcoholic cirrhosis (64 patients with ascites, classes B and C according to the Child-Pugh classification; and 17 without ascites, categorized as class A); 41 patients with previously untreated cirrhosis due to chronic hepatitis C (HCV--30 patients with ascites, classes B and C; and 11 without ascites, class A); 42 with alcoholic steatohepatitis and 46 with alcoholic steatosis. The control group consisted of 32 healthy volunteers. Twelve-lead ECG recordings were performed and selected parameters were measured. Results Significantly longer QT and QTc intervals and lower QRS voltage were found in patients with alcoholic and HCV cirrhosis compared to the controls. Significantly lower QRS voltage was found in subjects with ascites than in those without ascites. Removal of ascites significantly increased QRS voltage. Conclusions In cirrhosis, irrespective of etiology, ECG changes involved prolonged QT and QTc intervals and reduced QRS voltage. Prolonged QT and QTc intervals were not related to the severity of cirrhosis or to the presence of ascites. However, low QRS voltage was associated with the presence of ascites. Removal of ascites reverses low QRS voltage.

The role of adenosine A3 receptors and their distribution in the gastrointestinal tract have been widely investigated. Most of the reports discuss their role in intestinal inflammations. However, the role of adenosine A3 receptor agonist in pancreatitis has not been well established. The aim of this study is (Ed note: Purpose statements should be in present tense) to evaluate the effects of the adenosine A3 receptor agonist on the course of sodium taurocholate-induced experimental acute pancreatitis (EAP). The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C—control rats, I—EAP group, and II—EAP group treated with the adenosine A3 receptor agonist IB-MECA (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-d-ribofuronamide at a dose of 0.75 mg/kg b.w. i.p. at 48, 24, 12 and 1 h before and 1 h after the injection of 5 % sodium taurocholate solution into the biliary–pancreatic duct. Serum for α-amylase and lipase determinations and tissue samples for morphological examinations were collected at 2, 6, and 24 h of the experiment. In the IB-MECA group, α-amylase activity was decreased with statistically high significance compared to group I. The activity of lipase was not significantly different among the experimental groups but higher than in the control group. The administration of IB-MECA attenuated the histological parameters of inflammation as compared to untreated animals. The use of A3 receptor agonist IB-MECA attenuates EAP. Our findings suggest that stimulation of adenosine A3 receptors plays a positive role in the sodium taurocholate-induced EAP in rats.

Toczeń rumieniowaty układowy jest przewlekłą, zapalną chorobą tkanki łącznej o podłożu autoimmunologicznym, w przebiegu której mogą być zajęte różne narządy i układy. Objawy ze strony przewodu pokarmowego występują u 25–40% pacjentów z aktywną chorobą. Są one zwykle niespecyficzne i wynikają z istniejącej choroby bądź działań niepożądanych zastosowanej terapii. Zmiany w przewodzie pokarmowym mogą obejmować każdy z jego odcinków, a także dotyczyć wątroby i trzustki. W artykule przedstawiono najczęstsze i najcięższe objawy gastroenterologiczne w przebiegu tocznia rumieniowatego układowego, wśród nich toczniowe zapalenie naczyń krezki, enteropatię białkową, rozedmę pęcherzykową jelita, uszkodzenie wątroby i ostre zapalenie trzustki.

Background and aims. There is growing evidence that white adipose tissue is an important contributor in the pathogenesis of alcoholic liver disease (ALD). We investigated serum concentrations of total adiponectin (Acrp30), leptin, and resistin in patients with chronic alcohol abuse and different grades of liver dysfunction, as well as ALD complications.Materials and Methods. One hundred forty-seven consecutive inpatients with ALD were prospectively recruited. The evaluation of plasma adipokine levels was performed using immunoenzymatic ELISA tests. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications.Results. Acrp30 and resistin levels were significantly higher in patients with ALD than in controls. Lower leptin levels in females with ALD compared to controls, but no significant differences in leptin concentrations in males, were found. High serum Acrp30 level revealed an independent association with advanced liver dysfunction, as well as the development of ALD complications, that is, ascites and hepatic encephalopathy.Conclusion. Gender-related differences in serum leptin concentrations may influence the ALD course, different in females compared with males. Serum Acrp30 level may serve as a potential prognostic indicator for patients with ALD.

Background Non-alcoholic fatty liver disease (NAFLD) refers to a very wide clinical spectrum. Advanced fibrosis that accompanies disease leads to the development of cirrhosis and hepatocellular carcinoma. Thus, identification of patients with advanced fibrosis is essential. The aim of the present study was to compare the usefulness of NAFLD fibrosis and BARD scores in predicting fibrosis in NAFLD and to determine the risk factors of advanced fibrosis. Material/methods The study included 126 patients with NAFLD. Fibrosis in liver biopsy was scored on a 5-point scale. The BARD and the NAFLD fibrosis scores were compared with the biopsy findings. Results Liver biopsy revealed 27 patients with advanced and 99 with mild/moderate fibrosis. Advanced fibrosis was statistically significantly more common in older patients with obesity, AST/ALT ratio ≥0.8, diabetes mellitus, and thrombocytes ≤200 × 10³/L. Positive predictive value, negative predictive value and AUROC curve for BARD score, and NAFLD fibrosis score were 68.57%, 96.70%, 0.865 and 70.59%, 98.11%, 0.919, respectively. Conclusions Both scores are capable of ruling out advanced fibrosis and markedly reducing the need for liver biopsies in patients with NAFLD. Obesity, diabetes mellitus, thrombocytes ≤200 × 10³/L, advanced age and AST/ALT ratio ≥0.8 are the risk factors of advanced fibrosis.

Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA-IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA-IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (μg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA-IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre-/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.

Chronic pancreatitis (CP) is a necroinflammatory process characterized by loss of both exocrine and endocrine function. To date, the disease has been treated symptomatically. Real advances in CP management can be expected once the pathophysiology of the disease is elucidated and individual stages of its development are properly managed. A key role in the CP pathogenesis is played by activation of pancreatic stellate cells (PSCs) that cooperate with the remaining pancreatic cells. All these cells produce cytokines, growth factors, angiotensin and other substances, which paracrinally or autocrinally induce further, persistent activation of PSCs. The activated PSCs are capable of producing and modifying the extracellular matrix. An optimal therapeutic preparation should exert beneficial effects on all the above-mentioned phenomena observed in CP. The most promising treatment modalities include blocking of the renin-angiotensin system (RAS), activation of peroxisome proliferator-activated receptors gamma (PPAR-γ), influence on the remaining PSC signaling pathways, blocking of substances produced by activated PSCs, and antioxidants. The findings of many recent experimental studies are highly encouraging; however, their efficacy should be confirmed in well-designed clinical trials.

Purpose To assess the prevalence of spontaneous bacterial peritonitis (SBP) in asymptomatic patients with decompensated liver cirrhosis. Material and methods Patients (pts) with symptoms of decompensation of liver cirrhosis, ascites, and no signs indicating SBP were included to our study. Exclusion criteria include: 1/ clinical symptoms of infection, 2/ developing de novo or worsening hepatic encephalopathy, 3/ gastrointestinal bleeding within the last month, 4/ renal failure, 5/ antibiotic treatment or norfloxacin prophylaxis at admission. About 60 ml of ascitic fluid were drawn for lab examination. Pathologic assessment for atypical cells was also performed. Results 37 patients fulfilled inclusion criteria. Their mean age was 56.2 ± 12.1. The Child- Pugh classification revealed 13 (35.1%) patients of class B and 24 (64.9%) patients of class C. The mean Model for End-Stage Liver Disease score in this group was 16.6 ± 6.8. The mean ascitic protein content was 1.85 ± 1.09 g/dL and mean neutrophil count 144.8 ± 445.1/mm3. Ascitic fluid analysis revealed: signs of bacterascites in 6 of 37 (16.2%) pts; neutrocytic ascites in 1 of 37 (2.7%) pts; and 2 of 37 (5.4%) pts met criteria for SBP. C-reactive protein level was the best predictor of infection [SBP(+) 47.9 ± 40.9 versus SBP(-) 11.7 ± 5.1; p= 0.0005]. Conclusions The prevalence of SBP in asymptomatic cirrhotics with ascites is low. We observed the trend towards more frequent occurrence of the infection in patients suffered from severe liver disease (Child-Pugh C group).

Melatonin and L-tryptophan (Trp) are highly gastroprotective in humans, but no study has assessed their impact on healing of chronic gastroduodenal ulcers in humans. Three groups (A, B and C) of 14 idiopathic patients in each treatment group with gastroduodenal chronic ulcers were treated with omeprazole (20 mg twice daily) combined either with placebo (group A), melatonin (group B) or with Trp (group C). The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after initiation of therapy. Plasma melatonin, gastrin, ghrelin and leptin were measured by RIA. On day 7, omeprazole by itself (group A) had not healed any ulcers, but four ulcers were healed with omeprazole plus melatonin and two with omeprazole plus tryptophan. At day 21, all ulcers were healed in patients treated with melatonin or Trp, but only 10-12 ulcers were healed in placebo-treated patients. After treatment with omeprazole plus melatonin (group B) or Trp (group C), plasma melatonin levels rose several-fold above initial values. Plasma gastrin level also rose significantly during treatment with omeprazole plus melatonin or Trp, but it was also significantly increased in patients treated with omeprazole plus placebo. Plasma ghrelin levels did not change significantly after treatment with melatonin or Trp, while plasma leptin increased significantly in patients treated with melatonin or Trp but not with placebo. We conclude that melatonin or Trp, when added to omeprazole treatment, accelerates ulcer healing and this likely depends mainly upon the significant increments in plasma melatonin.

Summary Background This study sought to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats. Material/Methods Inflammation was induced in Wistar rats by a single rectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). The antagonist of PPARγ antagonist, bisphenol A diglycidyl ether (BADGE), was administrated intraperitoneally 120 mg/kg 4 times every other day. Rosiglitazone 8 mg/kg was administrated by gastric tube 4 times. Body weight was measured daily. After killing, the large intestinal tissue was weighed and collected for histopathologic and immunoenzymatic tests. Levels of IL-6, IL-10, and myeloperoxidase (MPO) were determined in serum and in intestinal homogenates. Results Rats receiving rosiglitazone had higher body weight, whereas large intestine weight/length ratio was lower; histology showed fewer inflammatory markers. Rats receiving TNBS and TNBS along with BADGE had more intensive inflammatory changes. Rosiglitazone alone decreased expression of IL-6; used with TNBS it decreased expression of MPO in intestinal tissue, yet did not increase the expression of IL-10. Decreased levels of MPO indicate reduced neutrophil-dependent immune response. The antagonist of PPAR-γ increased IL-6 in serum and decreased IL-10 in intestinal homogenates. Bisphenol A diglycidyl ether administrated to healthy animals increases serum IL-6 levels. Conclusions Rosiglitazone inhibits experimental inflammation; administration of its selective antagonist abolishes this protective influence. Rosiglitazone inhibits expression of proinflammatory IL-6 and does not affect IL-10. Agonists of PPARs-γ are possibilities for inflammatory bowel disease prevention. Exogenous substances blocking PPARs-γ may contribute to development or relapse of nonspecific inflammatory bowel diseases.

The toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) related to the upper gastrointestinal (GI) tract is well established. However, they may cause injury distal to the duodenum as well – to the small and large intestine and/or to other organs of the digestive system. Non-steroidal anti-inflammatory drugs induce small intestinal perforation, ulcers or strictures requiring surgery and inflammation with blood and protein loss called NSAID enteropathy. These drugs can exacerbate pre-existing large bowel disease (e.g. ulcerative colitis, diverticular disease) and precipitate relapse of inactive disease or the new onset of inflammatory bowel disease (IBD) with rapid resolution of symptoms on their withdrawal. They have been implicated in the development of microscopic colitis. Non-steroidal antiinflammatory drugs-associated toxicity of the small and large bowel is increasingly recognized in clinical practice, as enteroscopic procedures become more frequently used. Liver injury is an uncommon, but potentially lethal complication. It can occur with all NSAIDs, but diclofenac and sulindac seem to be most commonly associated with the problem. These drugs may contribute to acute fatty liver of pregnancy. Hepatotoxicity is likely due to an idiosyncratic reaction resulting from an immunological response or altered metabolic pathways. The major benefits of NSAIDs relate to reports of possible prevention, delay or regression of progress towards cancer of the colon, oesophagus, stomach as well as of cancer of the breast, lung, prostate and skin. Despite their promise, NSAIDs are not yet recommended for prevention or treatment of any cancer, because the balance of hazards and benefits from the treatment must be resolved in the designated patient population. Streszczenie Toksycznośc niesteroidowych lekow przeciwzapalnych (NLPZ) w stosunku do gornego odcinka przewodu pokarmowego jest dobrze udokumentowana. Mogą one jednak powodowac uszkodzenia rowniez dystalnie do dwunastnicy – w jelicie cienkim oraz grubym i/lub w innych narządach ukladu trawiennego. Niesteroidowe leki przeciwzapalne wywolują perforacje, owrzodzenia i przewezenia jelita cienkiego, ktore wymagają leczenia operacyjnego, oraz stan zapalny z utratą krwi i bialka, zwany enteropatią. Mogą zaostrzyc objawy podstawowej choroby jelita grubego (np. wrzodziejącego zapalenia jelita grubego, choroby uchylkowej), wtornie wzmagac aktywnośc choroby nieaktywnej lub indukowac pierwotny epizod nieswoistych zapalnych chorob jelit, z szybkim ustepowaniem objawow po odstawieniu leku. Sugeruje sie ich udzial w rozwoju mikroskopowego zapalenia jelita grubego. W praktyce klinicznej toksycznośc NLPZ w jelicie cienkim i grubym rozpoznaje sie coraz cześciej ze wzgledu na coraz powszechniejszą dostepnośc procedur endoskopowych. Uszkodzenie wątroby jest rzadkim, lecz potencjalnie śmiertelnym powiklaniem. Moze sie ono pojawic po uzyciu kazdego NLPZ, ale najcześciej problem ten wywolują diklofenak i sulindak. Niesteroidowe leki przeciwzapalne mogą brac udzial w ostrym stluszczeniu wątroby u kobiet w ciązy. Ich hepatoto ksycznośc jest prawdopodobnie reakcją idiosynkrazji w wyniku odpowiedzi immunologicznej lub zaburzen metabolicznych. Najwazniejsze korzyści z terapii NLPZ wykazaly raporty o mozliwej profilatyce, opoźnieniu lub regresji rozwoju raka w jelicie grubym, przelyku, zolądku, a takze raka piersi, pluc, gruczolu krokowego i skory. Mimo tych doniesien nie sformulowano dotychczas rekomendacji dla profilaktyki i leczenia NLPZ w przebiegu zadnego z tych nowotworow. Stosunek ryzyka do korzyści wynikający z takiego leczenia musi zostac oszacowany w badaniach w odpowiednich grupach chorych.

This investigation was designed to assess the effects of oral administration of melatonin (10 mg) and tryptophan (Trp) (500 mg) on fasting and postprandial plasma levels of melatonin, gastrin, ghrelin, leptin and insulin in 10 healthy controls and in age-matched patients with liver cirrhosis (LC) and portal hypertension. Fasting plasma melatonin levels in LC patients were about five times higher (102 +/- 15 pg/mL) than in healthy controls (22 +/- 3 pg/mL). These levels significantly increased postprandially in LC patients, but significantly less so in controls. Treatment with melatonin or L-Trp resulted in a further significant rise in plasma melatonin, both under fasting and postprandial conditions, particularly in LC patients. Moreover, plasma gastrin, ghrelin, leptin and insulin levels under fasting and postprandial conditions were significantly higher in LC subjects than in healthy controls and they further rose significantly after oral application of melatonin or Trp. This study shows that: (a) patients with LC and portal hypertension exhibit significantly higher fasting and postprandial plasma melatonin levels than healthy subjects; (b) plasma ghrelin, both in LC and healthy controls reach the highest values under fasting conditions, but decline postprandially, especially after oral application of melatonin or Trp; and (c) plasma melatonin, gastrin, ghrelin and insulin levels are altered significantly in LC patients with portal hypertension compared with that in healthy controls possibly due to their portal systemic shunting and decreased liver degradation.

To investigate the effects of ADH and ALDH gene polymorphism on the development of alcoholism, alcohol liver cirrhosis and alcohol chronic pancreatitis among Polish individuals.We determined the allele and genotype of ADH2, ADH3 and ALDH2 in 198 subjects: 57 with alcohol cirrhosis, 44 with alcohol chronic pancreatitis and 43 "healthy alcoholics"; 54 healthy non-drinkers served as controls. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method on white cell DNA.In the population examined the ADH2*1 allele frequency was 97.97%. The tests did not show the ADH2*3 allele. The ADH3*1 allele frequency was 57.07%. The ADH2*1 and the ADH3*1 alleles were statistically more common among patients who abuse alcohol in comparison with the controls. The ADH2*2 allele was not detected in any of the patients with chronic alcohol pancreatitis. The ADH2*1/*1 and the ADH3*1/*1 genotypes were statistically significantly more common among the patients who abuse alcohol than in the control group. All patients were ALDH2*1/*1 homozygotic. Patients with the ADH3*1 allele and the ADH3*1/*1 genotype started to abuse alcohol significantly earlier in comparison to the patients with the ADH3*2 allele and the ADH3*2 /*2 genotype.In the Polish population examined, the ADH3*1 allele and the ADH3*1/*1 genotype are conducive to the development of alcoholism, alcohol liver cirrhosis and alcohol chronic pancreatitis. However, the ADH2*2 allele is likely to protect against these conditions. Genetic polymorphism of ALDH2 shows no correlation with alcohol addiction or alcohol cirrhosis and alcohol chronic pancreatitis. The ADH3*1 allele and the ADH3*1/*1 genotype are conducive to alcohol abuse starting at a younger age.

Background: Genetic polymorphism of enzymes involved in alcohol metabolism plays a relevant role in etiopathogenesis of alcohol disease. The aim of the present study was to find in the Polish population the CYP2E1 genotypes that are likely to be responsible for higher susceptibility to alcohol disease of the liver and chronic alcohol pancreatitis. Methods: The CYP2E1 genotype and c1 and c2 alleles frequency were examined in 198 patients. Genotyping of the CYP2E1 was performed using polymerase chain reaction–restriction fragment length polymorphism methods on white cell DNA. Results: In the examined population encompassing 198 subjects, the c2 allele was present only in 1.5% of patients. It was found only in patients abusing alcohol. In the group of patients with alcoholic cirrhosis, it was present in 3.5% of cases, whereas in patients with chronic alcoholic pancreatitis, in 2.3%. The genotype c1/c2 was present in 3% of subjects. The genotype c2/c2 was not found in any patient. Heterozygotes c1/c2 were present only in patients consuming excessive amounts of ethanol; in 7% of patients with alcoholic cirrhosis and in 4.5% of those with chronic alcoholic pancreatitis. The c2 allele occurred only in men. None of the examined women had the genotype c1/c2. Conclusions: Our studies suggest that the frequency of the c2 alleles in Polish population is low. Because of their rare frequency, it is difficult to conclude explicitly that the presence of the c2 allele promotes alcoholic damage to alimentary organs among Poles. It seems, however, that they pose the risk of alcoholic cirrhosis; their role in chronic alcoholic pancreatitis is difficult to assess.

Aim: To find the ADH3 genotypes in the Polish population likely to be responsible for higher susceptibility to alcohol disease of the liver and chronic alcohol pancreatitis. Method: The ADH3 genotype and ADH3*1 and ADH3*2 alleles frequencies were examined in 198 patients. Genotyping of the ADH3 was performed using PCR-restriction fragment length polymorphism methods on a white cell DNA. Results: The genotype ADH3*1/ADH3*1 was found to be significantly more frequent in alcohol abusers compared with non-drinkers. The examinations of the group of alcohol abusers showed that the genotype ADH3*2/ADH3*2 occurred statistically significantly less frequently in patients with chronic pancreatitis than in those without alimentary lesions (healthy drinkers). The alleles ADH3*1 and genotype ADH3*1/ADH3*1 were significantly more frequent in men than in women, whereas alleles ADH3*2 and genotype ADH3*2/ADH3*2 were more common in women. Conclusions: The genotype ADH3*2/ADH3*2 is likely to be a protective factor for chronic pancreatitis. Variations in ADH3 genotypes may account for some of the differences in prevalence of alcohol dependence between genders in the Polish population.

BACKGROUND There is a growing evidence that matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases) play an important role in the pathogenesis of numerous disorders, especially with inflammatory etiology and extracellular matrix (ECM) remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation. DATA SOURCES We carried out a PubMed search of English-language articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases. RESULTS The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however, reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation. CONCLUSION The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases is observed, but the exact role of these enzymes demands further studies. (Hepatobiliary Pancreat Dis Int 2014;13:570-579)

Heterotopic or ectopic tissue is a congenital anomaly defined as the presence of the tissue outside its normal location. This tissue is usually discovered incidentally and may be asymptomatic or may present with non-specific gastrointestinal (GI) symptoms. Two types of heterotopic tissues, pancreatic and gastric, predominantly occur in the GI tract. The frequency of ectopic pancreas found in autopsy studies is approximately 0.5%-13.7%. Heterotopic pancreatic tissue can be located anywhere along the GI tract; the most common sites are the stomach (27.5%), duodenum (25.5%), colon (15.9%), esophagus, and Meckel`s diverticulum. It has been found in approximately one per 500 surgical procedures involving the upper GI tract. It can also occur in the gallbladder, biliary tract, spleen, liver, omentum, mesentery, lung and pelvis. Likewise, heterotopic gastric mucosa can occur anywhere along the GI tract yet its most common locations are different from those of heterotopic pancreatic tissue. In this paper we present heterotopy characteristics in particular locations. Gastric or pancreatic heterotopy, although rare, should be taken into consideration in differential diagnosis of unexplainable abdominal pain, bleeding from the GI tract or weight loss. Once heterotopy has been detected, appropriate treatment can be implemented which will reduce the risk of complications.

Angiogenesis is believed to be implicated in the pathogenesis of alcoholic liver disease (ALD). We aimed to explore the usefulness and accuracy of plasma angiogenic biomarkers for noninvasive evaluation of the severity of liver failure and ALD outcome. One hundred and forty-seven patients with ALD were prospectively enrolled and assessed based on their (1) gender, (2) age, (3) severity of liver dysfunction according to the Child-Turcotte-Pugh and MELD scores, and (4) the presence of ALD complications. Plasma levels of vascular endothelial growth factor (VEGF-A) and angiopoietins 1 and 2 (Ang1 and Ang2) were investigated using ELISAs. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Significantly higher concentrations of Ang2 and VEGF-A in ALD patients as compared to controls were found. There was no difference in Ang1 levels in both groups. A positive correlation of Ang2 levels with INR (Rho 0.66;P<0.0001) and its inverse correlation with plasma albumin levels (Rho –0.62;P<0.0001) were found. High Ang2 concentrations turned out to be an independent predictor of severe liver dysfunction, as well as hepatic encephalopathy and renal impairment. Ang2 possessed the highest diagnostic and prognostic potential among three studied angiogenesis-related molecules.

Background Ulcerative colitis (UC) is a chronic disease with periods of remission and recurrences. Dysfunction of the local immune response leads to chronic inflammation within the large intestine which triggers morphological changes in the intestinal wall as well as induces the synthesis of numerous factors that have an adverse impact on the bone metabolism. The aim of the study was to determine the expression of RANKL, OPG and IL-33 in mucosal biopsies of UC patients with long disease duration as well as serum level of these cytokines in the context of bone density and bone metabolism. Materials and methods The UC group consisted of 56 patients with average disease duration of 16 y. The control group comprised 37 healthy individuals. Local expression of cytokines was assessed in the biopsies of colonic mucosa by the real-time PCR and immunohistochemistry (IHC), and their serum concentration was measured by ELISA. Results The increased bone resorption observed in patients with UC was reflected by low bone density and high serum level of C-terminal telopeptide (CTX). Mucosal RANKL expression and serum concentration were similar in UC group and healthy subjects, however, UC patients had higher local expression of OPG and serum OPG concentration. Increased IL-33 gene expression was observed only in UC at the mRNA level. We propose that bone resorption in UC patients despite OPG up-regulation could be caused by IL-33-induced mucosal synthesis of a potent proinflammatory cytokine, such as TNF-α, known as a possible inducer of osteoclastogenesis in the way independent of RANKL.

To investigate large tumor suppressor 1 (LATS1) expression, promoter hypermethylation, and microsatellite instability in colorectal cancer (CRC).RNA was isolated from tumor tissue of 142 CRC patients and 40 colon mucosal biopsies of healthy controls. After reverse transcription, quantitative polymerase chain reaction (PCR) was performed, and LATS1 expression was normalized to expression of the ACTB and RPL32 housekeeping genes. To analyze hypermethylation, genomic DNA was isolated from 44 tumor CRC biopsies, and methylation-specific PCR was performed. Microsatellite instability (MSI) status was checked with PCR using BAT26, BAT25, and BAT40 markers in the genomic DNA of 84 CRC patients, followed by denaturing gel electrophoresis.Decreased LATS1 expression was found in 127/142 (89.4%) CRC cases with the average ratio of the LATS1 level 10.33 ± 32.64 in CRC patients vs 32.85 ± 33.56 in healthy controls. The lowest expression was found in Dukes' B stage tumors and G1 (well-differentiated) cells. Hypermethylation of the LATS1 promoter was present in 25/44 (57%) CRC cases analyzed. LATS1 promoter hypermethylation was strongly associated with decreased gene expression; methylated cases showed 162× lower expression of LATS1 than unmethylated cases. Although high-grade MSI (mutation in all three markers) was found in 14/84 (17%) cases and low-grade MSI (mutation in 1-2 markers) was found in 30/84 (36%) cases, we found no association with LATS1 expression.Decreased expression of LATS1 in CRC was associated with promoter hypermethylation, but not MSI status. Such reduced expression may promote progression of CRC.

Aim. Determination of risk factors relevant to 90-day prognosis in AH. Comparison of the conventional prognostic models such as Maddrey’s modified discriminant function (mDF) and Child-Pugh-Turcotte (CPT) score with newer ones: the Glasgow Alcoholic Hepatitis Score (GAHS); Age, Bilirubin, INR, Creatinine (ABIC) score, Model for End-Stage Liver Disease (MELD), and MELD-Na in the death prediction.Patients and Methods. The clinical and laboratory variables obtained at admission were assessed. The mDF, CPT, GAHS, ABIC, MELD, and MELD-Na scores’ different areas under the curve (AUCs) and the best threshold values were compared. Logistic regression was used to assess predictors of the 90-day outcome.Results. One hundred sixteen pts fulfilled the inclusion criteria. Twenty (17.4%) pts died and one underwent orthotopic liver transplantation (OLT) within 90 days of follow-up. No statistically significant differences in the models‘ performances were found. Multivariate logistic regression identified CPT score, alkaline phosphatase (AP) level higher than 1.5 times the upper limit of normal (ULN), and corticosteroids (CS) nonresponse as independent predictors of mortality.Conclusions. The CPT score, AP > 1.5 ULN, and the CS nonresponse had an independent impact on the 90-day survival in AH. Accuracy of all studied scoring systems was comparable.

Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA-IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA-IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (μg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA-IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre-/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.

Because of numerous limitations for liver biopsy, a noninvasive marker of liver cirrhosis is sought. Promising indicators seem to be matrix metalloproteinases (MMPs) that are responsible for degradation of extracellular matrix. The aim of the study was to evaluate the gelatinase activities (MMP-2 and MMP-9) in patients with different stages of alcoholic cirrhosis. Sixty-seven outpatients who presented various stages of alcoholic cirrhosis according to Child–Turcotte–Pugh criteria and 26 healthy control subjects were enrolled. Blood samples were collected for MMP-2 and MMP-9 activities. A significant decrease of serum MMP-2 activity was noted in stages B and C of cirrhosis in comparison with control. Serum MMP-9 activity did not depend on the stage of cirrhosis. The MMP-2 levels, but not those of MMP-9, may be of value in understanding the pathogenesis and progression of alcoholic cirrhosis.

Melatonin and its precursor, l-tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l-tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E(2), and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA induced gastric lesions and microbleeding. Gastric mucosal generation of PGE(2) was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan.

Alcohol dependence poses a serious medical and sociological problem. It is influenced by multiple environmental and genetic factors, which may determine differences in alcohol metabolism. Genetic polymorphism of the enzymes involved in alcohol metabolism is highly ethnically and race dependent. The purpose of this study was to investigate the differences, if present, in the allele and genotype frequency of alcohol dehydrogenase 1B (ADH1B), ADH1C and the microsomal ethanol-oxidizing system (MEOS/CYP2E1) between alcohol-dependent individuals and controls and also to determine if these genotypes cause a difference in the age at which the patients become alcohol dependent. The allele and genotype frequencies of ADH1B, ADH1C, and CYP2E1 were determined in 204 alcohol dependent men and 172 healthy volunteers who do not drink alcohol (control group). Genotyping was performed by PCR-RFLP methods on white cell DNA. ADH1B*1 (99.3%) and ADH1C*1 (62.5%) alleles and ADH1B*1/*1 (N = 201) and ADH1C*1/*1 (N = 85) genotypes were statistically more frequent among alcohol-dependent subjects than among controls (99.3 and 62.5%, N = 201 and 85 vs 94.5 and 40.7%, N = 153 and 32, respectively). Differences in the CYP2E1 allele and genotype distribution between groups were not significant. The persons with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes became alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes (28.08, 25.67 years vs 36.0, 45.05, 34.45 years, respectively). In the Polish men examined, ADH1C*1 and ADH1B*1 alleles and ADH1C*1/*1 and ADH1B*1/*1 genotypes favor alcohol dependence. The ADH1B*2 allele may protect from alcohol dependence. However, subjects with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes become alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes.

The purpose of this experiment was to investigate the role of PPAR ligands in the course of inflammation and of rosiglitazone, a PPAR-gamma-specific agonist, on the course of experimental acute pancreatitis (EAP).EAP was induced by administration of 5% sodium taurocholate injected into the pancreatic duct. The inflammatory activity was evaluated by biochemical scores (alpha-amylase, lipase, aminotransferases, and bilirubin), morphological changes (determined by light microscopy, H+E stained), and immunohistochemical reactions (ICAM, nitrotyrosine).Rosilgitazone administered in the course of EAP at a dose 50 mg/kg p.o. decreased the intensity of morphological changes (edema, inflammatory infiltrates, necrosis, and erythrocyte extravasations). In the rosiglitazone-treated animals all the biochemical parameters of EAP were statistically significantly decreased. Immunohistochemical reactions against ICAM-1 and nitrotyrosine showed that rosiglitazone decreased the intensity of inflammatory reactions in the groups of treated animals.PPAR-gamma agonists modulate the course of the inflammatory reaction. The administration of rosiglitazone decreased the intensity of the inflammatory process in the course of sodium taurocholate-induced EAP.

Unatoč nedavnim iskoracima u ispitivanju etiopatogeneze akutnog pankreatitisa (AP), još uvijek nisu objašnjeni svi čimbenici koji određuju nastup i tijek te bolesti. Istraživači se usredotočuju na ispitivanje čimbenika koji uvjetuju razvoj teškog AP, te razmatraju genetičku predispoziciju, vrstu mogućih odgovornih čimbenika kao i istodobno prisutna oboljenja. Najbitnija zadaća preostaje, međutim, procjena osjetljivosti i specifičnosti biokemijskih i seroloških biljega u dijagnozi i prognozi razvoja teškog APte njihova klinička dostupnost. Aktivnost lipaze u serumu je pouzdaniji dijagnostički biljeg AP, nego aktivnost serumske amilaze. Tripsinogen-aktivacijski peptid (TAP) omogućava ranu dijagnozu AP. Korisni predskazatelji težine bolesti mogu uključivati prokalcitonin i TAP u mokraći, interleukine 6 i 8 u serumu, 24-satnu polimorfonuklearnu elastazu, te 48-satni C-reaktivni protein. Istraživači se usredotočuju na potragu za najboljim mogućim prognostičkim čimbenikom AP. U kliničkoj se praksi, međutim, dijagnoza temelji na biološkim biljezima, kliničkoj procjeni i drugim laboratorijskim rezultatima koji su uključeni u Ransonovu ljestvicu ili APACHEII, te na slikovnim pretragama koje se koriste za određivanje pokazatelja težine bolesti kompjutorskom tomografijom (engl. computertomographyseverityindex, CTSI). Točnu prognozu tijeka AP nije moguće načiniti sve dok nisu određeni svi ti parametri kako bi se moglo započeti s najboljom mogućom terapijom., Despite recent advances in research on etiopathogenesis of acute pancreatitis (AP), not all factors that determine the onset and course of the disease have been explained. Researchers concentrate on investigating the factors conditioning the development of severe AP. They consider genetic predisposition, the type of possible responsible factors, and comorbidities. The most essential task, however, remains to be the assessment of sensitivity and specificity of biochemical and serological markers in diagnosis and prognosis of developing severe AP and their clinical availability. Serum lipase is a more reliable diagnostic marker of AP than serum amylase. Trypsinogen activation peptide (TAP) ensures early diagnosis of AP. Useful predictors of severity may include serum procalcitonin and urinary TAP, serum interleukins-6 and -8 and polymorphonuclear elastase at 24 h, and serum C-reactive protein (CRP) at 48h. Researchers concentrate on searching for the best possible prognostic factor of AP. In clinical practice, though diagnosis is based on biological markers, clinical assessment and other laboratory results included in Ranson scale or APACHE II and imaging investigations used to define computer tomography severity index (CTSI). Accurate prognosis of AP course cannot be made until all those parameters have been determined so that the best possible treatment can be undertaken.

The aim of the study was to analyse the prevalence of H. pylori infection in adult inhabitants of Lublin Province. The effects of living conditions and lifestyle on the infection frequency were evaluated. The study included 585 adults randomly chosen for the epidemiological analysis of H. pylori infection in the Lublin region within the project commissioned by the Ministry of Health (PCZ 08-09) and State Committee for Scientific Research (C007/P05/2000). The study was based on a personal questionnaire and determinations of anti/Hp antibodies in IgG class using the ELISA method. High titres of anti/Hp antibodies (24 IU/ml) were demonstrated in 78.5 % of the subjects. In Lublin Province the infected individuals constitute 72 % of inhabitants, in the big towns--74 % and in small towns--95 %. According to the place of birth: among those born in the country 87 % are infected, compared to 78.4 % in the small towns and 64 % in the big towns, respectively. Positive test results were observed in 79 % of farmers, 78 % of manual workers and 75 % of mental workers. The percentage of the affected neglecting basic hygienic rules exceeded 90 %. With increased frequency of hygienic measures the number of the H. pylori infected individuals decreased to 65 %. The prevalence of H. pylori infection among the inhabitants of the Lublin region is lower than that found in town inhabitants. Lublin Province shows the lowest level of H. pylori infection in Poland. The H. pylori infection is strongly affected by the lack of basic rules of personal hygiene and improper diet.

Congenital nonhemolytic hyperbilirubinemias (CNH) are quite rare pathology of liver. They occur most often in children, but are common in adults too. A common feature of congenital nonhemolytic hyperbilirubinemias is an abnormal serum bilirubin level without other abnormalities in routine liver functional tests. Liver histology on light microscopy is normal. Hereditary genetics defect of enzymes taking part in metabolism of bilirubin is the cause of CNH. They are divided into two groups: with unconjugated hyperbilirubinemia (Crigler-Najjar syndrome, Gilbert syndrome) and conjugated hyperbilirubinemia (Dubin-Johnson syndrome and Rotor syndrome). Because CNH in adults are benign disorders and the prognosis is excellent, patients do not require any specific therapy. Is important to take the differential diagnosis. Once the diagnosis of congenital nonhemolytic hyperbilirubinemia is confirmed, patients should be informed of the disease process and its benign nature to prevent needless work-up in the future. In present, CNH are treated as cosmetic defects and no therapy is applied.

In the recent years, the prevalence of adenocarcinomas of the esophagus has substantially increased. At present its prevalence in the USA is comparable to that of squamous carcinoma (5/100,000 a year). In 80-90% of cases esophageal adenocarcinoma is located in 1/3 of the lower esophagus and is mainly derived from Barrett's esophagus (BE). The role of Helicobacter pylori (Hp) infection in the pathogenesis of gastritis and gastric ulcer disease has been well known and documented. However, its role in the pathogenesis of esophageal reflux disease, its complications, particularly regarding the risk of Barrett's esophagus and adenocarcinoma is still being studied. The relation between Hp infection and BE has been discussed for many years. The importance of the problem is warranted by the wide prevalence of both Hp infection and reflux disease in the population. The above mentioned findings confirm the protective effects of Hp infection in BE. Despite numerous studies some doubts concerning the relations between Hp infection and BE are still to be explained.

The Helicobacter pylori infection is considered the most frequent factor of morbidity and mortality in the diseases of the upper alimentary tract. It is responsible for duodenal and gastric ulcers. It may contribute to the development of MALT lymphoma and gastric carcinoma. The H.p. infection is a widespread phenomenon, its intensification is associated with the socioeconomic status and increases with age. The aim of the study is to analyse the epidemiological trends of the H.p. infection, the effects of environmental factors, lifestyle, diet and sanitary habits on the incidence of H.p. infection in the adult population of the Lublin region. The study included 585 adults randomly chosen for epidemiological analysis within the project ordered by the Ministry of Health and State Committee for Scientific Research. The personal questionnaires were completed and serum levels of antibodies against H.p. were determined. The positive results were found in 78.52% of the examined participants. In the youngest group, the positive result was observed in 46% of cases. In the successive age groups a systematic increase in the number of the infected was found--from 46% to 100%. The highest number of the infected individuals live in provincial towns--94.6%, the lowest--in the country--71.9%. The infections are significantly affected by sanitary conditions: poor personal hygiene--the incidence about 90%. The infection incidence is also affected by alcohol consumption--increases with consumption of high-grade alcohols--82.4% (compared to 67.5% among non-drinkers) and decreases in those drinking low-grade alcohols (beer)--75.8% (84.9% in non-drinkers). No effects of the economic status and education on the H.p. infection incidence were observed.

The aim of our study was to check the significance of portal blood velocity /PBV/ in evaluation of the severity of liver disease. Duplex doppler sonography evaluation of PBV was performed in 20 patients (pts) with liver cirrhosis (7 women, 13 men, aged 34-75) and 10 pts with normal liver function (controls). We checked it during fasting and 30 minutes after a meal. The diagnosis of liver cirrhosis was based on clinical, laboratory and sonographic criteria. The severity of liver cirrhosis was classified according the Child-Pugh score as class A--6 pts.; class B--10 pts. and class C--4 pts. The lowest values of the mean baseline PBV (during fasting) were observed in cirrhotic pts class C (15.9+/-4.2 cm/s vs class B 18,1+/-7.8 cm/s vs class A 20.4+/-8.6 cm/s vs controls 21.6+/-3.8 cm/s). A similar situation appeared after our evaluation of PBV values in the postprandial state (class C 16.5+/-4.8 cm/s vs class B 19.8+/-9.1cm/s vs class A 22.4+/-6.4 cm/s vs controls 29.6+/-10.6 cm/s). The increment of PBV after a meal in pts with the Child-Pugh class C was significantly diminished compared to control group (0.6+/-4.1cm/s vs 8.0+/-5.2 cm/s; p0.05). We concluded that the postprandial portal blood velocity assessment is useful for evaluation of the severity of liver disease.

The aim of our study was assessment of the long-term influence of interferon-alpha (IFN-alpha) treatment on the serum marker of the hepatocarcinogenesis level-alpha-fetoprotein (AFP)-in patients (pts) with chronic viral hepatitis (cvh) B and C. Thirty seven pts (21 with HCV and 16 with HBV infection (20 women, 17 men, aged 24-62) were included in the study. Pts were administered IFN-alpha in the dose of 9-15 MU per week, thrice a week, for 16 weeks (HBV group) or 24-52 weeks (HCV group). Effectiveness of IFN-alpha treatment was evaluated on the basis of the HBV DNA and HCV RNA level in blood. The serum AFP values were determined before and 4-7 years after IFN-alpha treatment. The baseline serum AFP level was increased in 26 out of 37 pts (70%) (14/21 from HCV group; 12/16 from HBV group). After the 4-7 years' follow-up it remained increased only in 2 out of 37 pts (5%). AFP values significantly decreased after IFN-alpha treatment (17.58+/-19.09 IU/ml vs 7.95+/-21.78 IU/ml; p0.05; normal range 0-5 IU/ml) in both HBV and HCV, responder and non- responder groups. These results support the hypothesis that IFN-alpha therapy could diminish the risk of liver carcinogenesis in pts with cvh B and C. It significantly decreases the serum AFP level. Its beneficial effect was observed both in responders and in non-responders.

Due to their complex and not fully known etiopathogenesis as well as difficulties in treatment, chronic hepatitis and cirrhosis still remain one of the main problems of hepatologists. Nowadays, the use of IFN alpha is considered the most effective method of treatment in chronic hepatitis. Recently, a new property of IFN, i.e. its effects on the reduction of fibrosis, has been discovered. The aim of the paper was to examine the effects of IFN alpha on biochemical parameters (AlAt and AspAt activities), on the metabolic function of the liver and its morphologic picture observed under the light and electron microscope after the 3- and 6-week CCl4-induced damage. The experiments were carried out in Wistar male rats. To evaluate the liver function, the test of aminophenazone elimination in the isolated perfused rat livers was used according to Miller modified by Hafte. Additionally, AspAt and AlAt activities were determined. The liver specimens were analysed under the light and electron microscope and using immunohistochemical methods. The findings show that after the 3-week CCl4-induced liver damage, IFN alpha does not significantly affect AlAt and AspAt activities, irrespective of the dose used. IFN alpha administered after the 6-week damage significantly changes those activities when the doses used are high. It was found that carbon tetrachloride does not result in evident cirrhotic changes, however it activates Ito cells, causes focal retraction of the stroma and fibrosis. The increased number of Ito cells in Disse's space observed in immunohistochemical and ultrastructural examinations is indicative of the activation of liver fibrotic processes following CCl4 administration in both variants used. IFN alpha substantially weakens fibrogenesis of the CCl4-damaged liver which is visible in the decreased number of Ito cells and weaker expression of the stroma retraction. Moreover, IFN alpha administered to the experimental animals after the CCl4-induced injury of the liver increases aminophenazone clearance, especially when used in higher doses. Positive effects of IFN confirmed in the studies suggest that the drug may be used in patients with chronic hepatitis and early cirrhosis since it is likely not only to eliminate the virus but also to improve the liver function and reduce fibrosis.

The experiment was carried out on mature Wistar male rats. The animals from experimental group I received Atorvastatin in the dose 0.28 mg/24 h for 3 weeks. Experimental group II received 20% ethanol ad libitum apart from Atorvastatin. Ultrastructural examinations of pancreatic exocrine cells showed the stimulation of secretory processes in cells of animals receiving Atorvastatin and considerable damage of cell organelles in experimental group II, more intense than in the pancreas of control animals which drank ethanol.