Elevated miRNA Inversely Correlates with E-cadherin Gene Expression in Tissue Biopsies from Crohn Disease Patients in contrast to Ulcerative Colitis Patients.

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.

Results of screening in Lublin Province, Poland, for colorectal cancer and neoplastic polyps - the role of environmental factors.

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.

Expression of death receptor 3 on peripheral blood mononuclear cells differes in adult IBD patients and children with newly diagnosed IBD.

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.

In Vitro Proinflammatory Polarization of Macrophages Isolated from Hepatocarcinogenic Stage in Humans and Rats.

Macrophages have multiple functions in both inhibiting and promoting hepatocarcinogenesis, which are dependent on their phenotypes. Thus, we were interested in clarifying the 'training' proinflammatory effects exerted by barley ß-glucan (BBG) on monocyte-derived macrophages from patients with hepatocellular carcinoma (HCC-Mfs). After isolation and differentiation HCC-Mfs were treated with different concentrations of BBG and functional assays were then conducted after 24 h, and 3 and 5 days of incubation. The release of reactive oxygen species, arginase concentration and cell morphology were analyzed. Under the influence of BBG neoplastic cells slightly elongated and dendric-like filopodia were observed. In HCC-Mfs, the significant generation of NO and O2- was seen on days 3 and 5 of culture, concomitantly with significant depletion (p<0.05) of arginase activity. In summary, we showed that HCC-Mfs, 'trained' in a BBG microenvironment keep a highly dynamic plasticity, together with their proinflammatory polarization, expressed by reactive oxygen species and reactive nitrogen intermediates (RNI) augmentation.

QT Interval Prolongation and QRS Voltage Reduction in Patients with Liver Cirrhosis.

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.

Quality of life of patients with irritable bowel syndrome before and after education.

OBJECTIVES: 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). 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.

Prognostic Significance of the Systemic Inflammatory and Immune Balance in Alcoholic Liver Disease with a Focus on Gender-Related Differences.

OBJECTIVES: Mechanisms of immune regulation in alcoholic liver disease (ALD) are still unclear. The aim of our study was to determine an impact of Th17 / regulatory T (Treg) cells balance and its corresponding cytokine profile on the ALD outcome. Possible gender-related differences in the alcohol-induced inflammatory response were also assessed. MATERIALS AND METHODS: 147 patients with ALD were prospectively recruited, assigned to subgroups based on their gender, severity of liver dysfunction and presence of ALD complications at admission, and followed for 90 days. Peripheral blood frequencies of Th17 and Treg cells together with IL-1beta, IL-6, IL-17A, IL-23, and TGF-beta1 levels were investigated. Flow cytometry was used to identify T cell phenotype and immunoenzymatic ELISAs for the corresponding cytokine concentrations assessment. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. RESULTS: IL-17A, IL-1beta, IL-6 levels were significantly increased, while TGF-beta1 decreased in ALD patients. The imbalance with significantly higher Th17 and lower Treg frequencies was observed in non-survivors. IL-6 and TGF-beta1 levels differed in relation to patient gender in ALD group. Concentrations of IL-6 were associated with the severity of liver dysfunction, development of ALD complications, and turned out to be the only independent immune predictor of 90-day survival in the study cohort. CONCLUSIONS: We conclude that IL-6 revealed the highest diagnostic and prognostic potential among studied biomarkers and was related to the fatal ALD course. Gender-related differences in immune regulation might influence the susceptibility to alcohol-associated liver injury.

The genetic predisposition and its impact on the diabetes mellitus development in patients with alcoholic chronic pancreatitis.

The most common cause of chronic pancreatitis (CP) is alcohol abuse. The aim of the present study was to identify patients with genetic predisposition to CP abusing alcohol. The question posed was whether CP manifests at a younger age and diabetes mellitus develops earlier in individuals with genetic predisposition. The study encompassed 79 patients with alcoholic chronic pancreatitis (ACP) and control group (100 persons). The following mutations were determined: R122H and N29I of PRSS1 and N34S of SPINK1 as well as E366K and E288V of SERPINA 1. No R122H and N291 mutations were observed in the group of ACP patients and in controls. Moreover, there was no E288V mutation. In 79 ACP patients, six SPINK 1 (N34S/wt) mutations were observed. In the control group, one heterozygous SPINK 1N34S gene mutation was found (P = 0.0238). Two PiZ mutations were identified in patients with ACP and one analogical mutation in controls. Amongst patients with ACP as well as SPINK1 and PiZ mutations, the onset of disease was observed earlier and developed earlier. The prevalence of SPINK1 mutation is higher in patients with ACP than in healthy populations. This mutation together with the effects of alcohol accelerates the development of ACP and of diabetes mellitus.

Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases.

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.

Pancreatic and gastric heterotopy in the gastrointestinal tract.

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-related biomarkers in patients with alcoholic liver disease: their association with liver disease complications and outcome.

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.

Association of serum adiponectin, leptin, and resistin concentrations with the severity of liver dysfunction and the disease complications in alcoholic liver disease.

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.

Alkaline phosphatase: the next independent predictor of the poor 90-day outcome in alcoholic hepatitis.

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.

[Serum iron parameters in chronic liver diseses]. / Parametry gospodarki zelazem w przewleklych chorobach watroby.

UNLABELLED: Iron is an essential micronutrient of almost all organisms, which is involved in many metabolic processes. Disorders of serum iron balance that relate mainly to its deficiency are frequently observed in patients with liver diseases. The aim of the study was the evaluation of serum iron parameters in patients with different chronic liver diseases and analysis of the relationships between serum level of iron, ferritin and transferrin in women and men in groups examined. MATERIAL AND METHODS: The study includes 424 patients: 151 with alcoholic liver cirrhosis (ALC), 53 with nonalcoholic fatty liver disease (NAFLD), 54 with autoimmune hepatitis (AIH), 19 patients with hepatocellulare cancer (HOC), 34 with primary biliaris cirrhosis (PBC), 39 with chronic HCV hepatitis, 48 with chronic HBV hepatitis, 15 with primary sclerosans cholangitis (PSC) and 11 patients with hemochromatosis. Forty two healthy volunteers were the control group. RESULTS: The highest mean serum level of iron was observed in patients with hemochromatosis and was 278.56 +/- 25.04 mg/dl. The mean level of iron was statistically significant different in patients with HCC in comparison to the patients with ALC (p = 0.0000), with AIH (p = 0.0108) and NAFLD (p = 0.00768). The mean level of ferritin was statistically significantly higher among patients with hemochromatosis (p = 0.0000), with ALC (p = 0.0037) and NAFLD (p = 0.0442) than in the controls. Patients with AIH, HCC, HCV infection, PSC and hemochromatosis showed higher serum level of transferin than the controls (p = 0.0000). The mean level of iron and ferritin was lowerin women than in men in the patients with ALC (p = 0.0088, p = 0.0018 respectively). The mean level of ferritin was significantly lower in men than in women among patients with NAFLD. (p = 0.0065). There were no statistically significant differences in the mean level of examined parameters between the sexes. CONCLUSION: Reduced serum level of iron is observed in chronic liver diseases. Elevated ferritin level is typical for patients with ALC and NAFLD. Differences in the level of iron, ferritin and transferin between men and women concemrn the patients with ALC while among patients with NAFLD only ferritin level differences are found.

Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation.

AIM: To investigate large tumor suppressor 1 (LATS1) expression, promoter hypermethylation, and microsatellite instability in colorectal cancer (CRC). METHODS: 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. RESULTS: 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. CONCLUSION: Decreased expression of LATS1 in CRC was associated with promoter hypermethylation, but not MSI status. Such reduced expression may promote progression of CRC.

The effects of the adenosine A3 receptor agonist IB-MECA on sodium taurocholate-induced experimental acute pancreatitis.

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 [corrected] 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.

Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin.

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.

The BARD score and the NAFLD fibrosis score in the assessment of advanced liver fibrosis in nonalcoholic fatty liver disease.

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.

The decrease of serum MMP-2 activity corresponds to alcoholic cirrhosis stage.

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.

Activated and inactivated PPARs-γ modulate experimentally induced colitis in rats.

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.