222 results on '"Elias A. Kouroumalis"'
Search Results
2. Comparative evaluation of ALBI, MELD, and Child-Pugh scores in prognosis of cirrhosis: is ALBI the new alternative?
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Elias A. Kouroumalis, Dimitra Sifaki-Pistolla, Eleni Orfanoudaki, and Maria Fragaki
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medicine.medical_specialty ,Cirrhosis ,Child-Pugh ,Population ,Gastroenterology ,albumin-bilirubin score ,03 medical and health sciences ,chemistry.chemical_compound ,Liver disease ,0302 clinical medicine ,Model for End-Stage Liver Disease ,Internal medicine ,medicine ,model for end-stage liver disease ,education ,education.field_of_study ,Creatinine ,business.industry ,Hazard ratio ,Area under the curve ,medicine.disease ,Confidence interval ,body regions ,chemistry ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Original Article ,business - Abstract
Background: The existence of reliable prognostic indices is of paramount importance in the management of cirrhosis. Both the model for end-stage liver disease (MELD) score and the older Child-Pugh (CP) scores are widely used. The albumin-bilirubin (ALBI) score, initially used in hepatocellular carcinoma, has not been thoroughly investigated in cirrhosis. The aim of this study was to compare the prognostic accuracy of ALBI, MELD, MELD with sodium (MELD-Na), CP, and the corrected for creatinine CP scores in a genetically homogeneous Cretan cirrhotic population. Methods: One hundred ninety-five outpatients or hospitalized cirrhotics (127 male, median age 66 years) were studied over a period of 2 years and ALBI, platelet-albumin-bilirubin, MELD, MELD-Na, CP score, and 2 types of modified CP score (CP-I and CP-II) with serum creatinine were calculated and correlated with survival. Results: ALBI had an optimum balance between sensitivity and specificity (area under the curve 0.704, 95% confidence interval [CI] 0.630-0.778) compared to the other scores. In the multivariate analysis, the only factors independently associated with death were the ALBI score (hazard ratio [HR] 2.51, 95%CI 1.69-3.73; P
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- 2019
3. Association of smoking with liver fibrosis and mortality in primary biliary cholangitis
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Elias A. Kouroumalis, Aikaterini Mantaka, Dimitrios Samonakis, A. Voumvouraki, Mairi Koulentaki, Maria Tzardi, and Dimitra Sifaki-Pistolla
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Male ,0301 basic medicine ,medicine.medical_specialty ,Passive smoking ,Multivariate analysis ,Alcohol Drinking ,Biopsy ,Population ,Kaplan-Meier Estimate ,medicine.disease_cause ,Logistic regression ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Severity of illness ,medicine ,Humans ,education ,Aged ,education.field_of_study ,Greece ,Hepatology ,medicine.diagnostic_test ,Liver Cirrhosis, Biliary ,business.industry ,Smoking ,Gastroenterology ,Odds ratio ,Middle Aged ,medicine.disease ,030104 developmental biology ,Liver ,Liver biopsy ,Female ,Tobacco Smoke Pollution ,030211 gastroenterology & hepatology ,Steatosis ,business ,Follow-Up Studies - Abstract
Background The outcome of primary biliary cholangitis (PBC) is affected by both genetic and environmental factors. Objective The aim of this study was to study the effect of smoking on liver histology and mortality in a genetically homogeneous population having PBC. Patients and methods Smoking and drinking habits at diagnosis (based on standard criteria) were recorded in 171 Cretan patients with PBC (163 women). A total of 148 patients had a liver biopsy. Odds ratios were calculated with logistic regression analysis. Kaplan-Meier curves were used for mortality estimation. Results Smoking was associated with alcohol consumption of more than 20 g/day [adjusted odds ratio (AOR)=2.20, 95% CI: 1.029-4.099], severe steatosis (AOR=5.31, 95% CI: 2.019-9.919), and fibrosis stage F3-F4 (AOR=1.21, 95% CI: 1.015-3.031). Heavy smoking, years of passive smoking, and serious necroinflammatiοn were independent factors associated with advanced fibrosis after adjustment for sex, age, BMI, and alcohol consumption in multivariate analysis. For every pack-year increase in smoking intensity, there was a 3.2 times higher likelihood of advanced fibrosis (95% CI: 2.018-6.294). Increased mortality was found in smokers with advanced PBC. Conclusion There is an association between smoking, whether active or passive, and advanced fibrosis in PBC. Mortality is increased in smokers with advanced disease at presentation.
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- 2018
4. Autophagy in liver diseases
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Dimitrios Samonakis, Aikaterini Augoustaki, Elias A. Kouroumalis, and Argryro Voumvouraki
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Cell ,Lipophagy ,Autoimmune hepatitis ,Review ,Liver sinusoidal cells ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Fatty liver disease ,Mitophagy ,medicine ,Autophagy ,Hepatology ,business.industry ,Liver cell ,Fatty liver ,medicine.disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hepatic stellate cell ,Cancer research ,030211 gastroenterology & hepatology ,business - Abstract
Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms. Damaged organelles, lipids and proteins are degraded in the lysosomes and their elements are re-used by the cell. Investigations on autophagy have led to the award of two Nobel Prizes and a health of important reports. In this review we describe the fundamental functions of autophagy in the liver including new data on the regulation of autophagy. Moreover we emphasize the fact that autophagy acts like a two edge sword in many occasions with the most prominent paradigm being its involvement in the initiation and progress of hepatocellular carcinoma. We also focused to the implication of autophagy and its specialized forms of lipophagy and mitophagy in the pathogenesis of various liver diseases. We analyzed autophagy not only in well studied diseases, like alcoholic and nonalcoholic fatty liver and liver fibrosis but also in viral hepatitis, biliary diseases, autoimmune hepatitis and rare diseases including inherited metabolic diseases and also acetaminophene hepatotoxicity. We also stressed the different consequences that activation or impairment of autophagy may have in hepatocytes as opposed to Kupffer cells, sinusoidal endothelial cells or hepatic stellate cells. Finally, we analyzed the limited clinical data compared to the extensive experimental evidence and the possible future therapeutic interventions based on autophagy manipulation.
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- 2020
5. Impact of Silymarin in individuals with nonalcoholic fatty liver disease: A systematic review and meta-analysis
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Georgios Kalopitas, Ioannis Doundoulakis, Christina Antza, Georgios Germanidis, Myrto Samara, Michail Chourdakis, Elias A. Kouroumalis, and Antonis Siargkas
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0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,030209 endocrinology & metabolism ,Placebo ,Chronic liver disease ,Gastroenterology ,Transaminase ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Aspartate Aminotransferases ,education ,education.field_of_study ,030109 nutrition & dietetics ,Nutrition and Dietetics ,business.industry ,Alanine Transaminase ,medicine.disease ,Meta-analysis ,business ,Body mass index ,Silymarin - Abstract
Objectives Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting a significant proportion of the general population. Recently, randomized clinical trials have been conducted examining the efficacy of silymarin in individuals with NAFLD, with conflicting results. The aim of this meta-analysis was to evaluate the efficacy of silymarin in the treatment of NAFLD by examining changes in liver biochemistry, body mass index, and liver histology. Methods We searched major electronic databases PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, as well as gray-literature sources, up to June 2020 for randomized clinical trials examining the efficacy of treatment with silymarin in individuals with NAFLD compared to placebo. The primary outcomes were changes in the mean values of transaminases (alanine aminotransferase and aspartate aminotransferase). Secondary outcomes included changes in body mass index and liver histology. Quality analysis was performed with the risk-of-bias tool 2.0. We synthesized results using weighted mean differences for continuous outcomes, along with 95% confidence intervals. Results In the meta-analysis, eight randomized clinical trials were included. A cutoff level of 0.05 was considered to provide statistically significant results. Silymarin treatment led to a statistically significant greater reduction in the levels of transaminases compared to placebo, irrespective of weight loss. Conclusions Silymarin seems to be effective in reducing transaminase levels in individuals with NAFLD. Despite the statistical benefits, we call attention to potential flaws related to the quality of the included studies. Further well-designed studies should be carried out to examine whether this reduction in transaminase levels corresponds to histologic improvement.
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- 2020
6. Understanding the Interplay between COX-2 and hTERT in Colorectal Cancer Using a Multi-Omics Analysis
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Elias A. Kouroumalis, Apostolos Zaravinos, George Notas, Styliani Vederaki, Thivi Vasilakaki, Aikaterini Tsavari, T. Theodosopoulos, and Georgios D. Ayiomamitis
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0301 basic medicine ,Cancer Research ,Telomerase ,Stromal cell ,Colorectal cancer ,PTGS1 ,PGE2 ,colorectal cancer ,Biology ,medicine.disease_cause ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Telomerase reverse transcriptase ,Oncogene ,COX-2 ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,DNA methylation ,Cancer research ,KRAS ,hTERT - Abstract
Background: Cyclooxygenase 2 (COX-2) is involved in the initial steps of colorectal cancer (CRC) formation, playing a key role in the catalysis of arachidonic acid to prostaglandin E2 (PGE2). The human telomerase reverse transcriptase (hTERT or TERT) also plays an important role in colorectal cancer growth, conferring sustained cell proliferation and survival. Although hTERT induces COX-2 expression in gastric and cervical cancer, their interaction has not been investigated in the context of CRC. Methods: COX-2, PGE2 levels, and telomerase activity were evaluated by immunohistochemistry, ELISA, and TRAP assay in 49 colorectal cancer samples. PTGS1, PTGS2, PTGES3, TERT mRNA, and protein levels were investigated using RNA-seq and antibody-based protein profiling data from the TCGA and HPA projects. A multi-omics comparison was performed between PTGS2 and TERT, using RNAseq, DNA methylation, copy number variations (CNVs), single nucleotide polymorphisms (SNPs), and insertions/deletions (Indels) data. Results: COX-2 expression was positive in 40/49 CRCs, bearing cytoplasmic and heterogeneous staining, from moderate to high intensity. COX-2 staining was mainly detected in the stroma of the tumor cells and the adjacent normal tissues. PGE2 expression was lower in CRC compared to the adjacent normal tissue, and inversely correlated to telomerase activity in right colon cancers. COX-1 and COX-2 were anticorrelated with TERT. Isoform structural analysis revealed the most prevalent transcripts driving the differential expression of PTGS1, PTGS2, PTGES3, and TERT in CRC. COX-2 expression was significantly higher among B-Raf proto-oncogene, serine/threonine kinase, mutant (BRAFmut) tumors. Kirsten ras oncogene (KRAS) mutations did not affect COX-2 or TERT expression. The promoter regions of COX-2 and TERT were reversely methylated. Conclusions: Our data support that COX-2 is involved in the early stages of colorectal cancer development, initially affecting the tumor&rsquo, s stromal microenvironment, and, subsequently, the epithelial cells. They also highlight an inverse correlation between COX-2 expression and telomerase activity in CRC, as well as differentially methylated patterns within the promoter regions of COX-2 and TERT.
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- 2019
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7. GABAA receptor polymorphisms in alcohol use disorder in the GWAS era
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Mairi Koulentaki and Elias A. Kouroumalis
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0301 basic medicine ,Pharmacology ,Genetics ,Candidate gene ,GABAA receptor ,Single-nucleotide polymorphism ,Genome-wide association study ,Alcohol use disorder ,Heritability ,Biology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine ,Etiology ,Receptor ,030217 neurology & neurosurgery - Abstract
Alcohol use disorder (AUD) is a chronic, relapsing, neuro-psychiatric illness of high prevalence and with a serious public health impact worldwide. It is complex and polygenic, with a heritability of about 50%, and influenced by environmental causal heterogeneity. Risk factors associated with its etiology have a genetic component. GABA (γ-aminobutyric acid) is a major inhibitory neurotransmitter in mammalian brain. GABAA receptors are believed to mediate some of the physiological and behavioral actions of alcohol. In this critical review, relevant genetic terms and type and methodology of the genetic studies are briefly explained. Postulated candidate genes that encode subunits of GABAA receptors, with all the reported SNPs, are presented. Genetic studies and meta-analyses examining polymorphisms of the GABAA receptor and their association with AUD predisposition are presented. The data are critically examined with reference to recent GWAS studies that failed to show relations between GABAA receptors and AUD. Restrictions and perspectives of the different findings are discussed.
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- 2018
8. PO4-11A NATURAL HISTORY STUDY OF DECOMPENSATED ALCOHOLIC CIRRHOSIS IN CRETE. RECENT IMPROVEMENT IN SURVIVAL
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M Tzardi, Elias A. Kouroumalis, M Koulentaki, Ioannis A. Mouzas, E Matrella, E Theodoraki, D Samonakis, E Orfanoudaki, and A Augoustaki
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medicine.medical_specialty ,Alcoholic liver disease ,business.industry ,medicine ,General Medicine ,Intensive care medicine ,medicine.disease ,business ,Natural history study - Published
- 2017
9. Biomarkers for primary biliary cholangitis: current perspectives
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Demetrius Samonakis, Argyro Voumvouraki, and Elias A. Kouroumalis
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medicine.medical_specialty ,Treatment response ,autoantibodies ,Intrahepatic bile ducts ,Disease ,Review ,Gastroenterology ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,proteomics ,Fibrosis ,Internal medicine ,medicine ,Hepatology ,medicine.diagnostic_test ,business.industry ,primary biliary cholangitis ,Autoantibody ,treatment response ,medicine.disease ,microRNAs ,030220 oncology & carcinogenesis ,Liver biopsy ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Rare disease - Abstract
Primary biliary cholangitis (PBC) is a chronic progressive cholestatic disease characterized by destruction of small- and medium-sized intrahepatic bile ducts. It is no longer a rare disease, since many new asymptomatic cases are incidentally identified. Liver biopsy is diagnostically critical but not always feasible or practical to be performed. Many potential, noninvasive, markers have been proposed to replace liver biopsy and further provide the assessment of disease severity and ultimate prognosis. In this review, we evaluated serum biomarkers proposed for diagnosis, extent of fibrosis, disease prognosis and attempts for early prediction of treatment response. Older biochemical and immunological markers are presented along with recent reports including the role of microRNAs and promising results based on proteomics and metabolomics.
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- 2018
10. Portal vein thrombosis in cirrhosis: diagnosis, natural history, and therapeutic challenges
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Aikaterini Augoustaki, Aikaterini Mantaka, Elias A. Kouroumalis, and Dimitrios Samonakis
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anticoagulants ,medicine.medical_specialty ,Cirrhosis ,genetic structures ,medicine.drug_class ,Review Article ,direct oral anticoagulants ,behavioral disciplines and activities ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Disease severity ,mental disorders ,medicine ,Intensive care medicine ,business.industry ,cirrhosis ,Anticoagulant ,Gastroenterology ,bleeding ,medicine.disease ,Portal vein thrombosis ,Thrombosis ,Natural history ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business ,Complication ,human activities ,psychological phenomena and processes - Abstract
Portal vein thrombosis (PVT) is a frequent complication in cirrhosis and its prevalence increases with disease severity. Several factors are involved in the development and progression of PVT. The challenge for the management of PVT is the precise evaluation of the bleeding risk as opposed to life-threatening extension of thrombosis. Nevertheless, the impact on the progression and outcome of liver disease is unclear. A critical evaluation of the available data discloses that treating PVT in cirrhotics is safe and effective. However, there are open issues, such as which anticoagulant could represent a safer therapeutic option, and when and for how long this treatment should be administered to cirrhotic patients with PVT.
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- 2018
11. Angiodrastic Chemokines in Colorectal Cancer: Clinicopathological Correlations
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Adamantia Zizi-Sermpetzoglou, George Ayiomamitis, George Emmanouil, Maria Tzardi, Andrew Moursellas, Elias A. Kouroumalis, and A. Voumvouraki
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Chemokine ,Article Subject ,Colorectal cancer ,MLH1 ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Interleukin 8 ,Dukes' Classification ,RC254-282 ,Survival analysis ,Demography ,Neoplasm Staging ,QH573-671 ,biology ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell Biology ,General Medicine ,medicine.disease ,Survival Analysis ,Neoplasm Proteins ,030104 developmental biology ,030220 oncology & carcinogenesis ,CXCL6 ,biology.protein ,Molecular Medicine ,Histopathology ,Female ,Chemokines ,Cytology ,business ,Colorectal Neoplasms ,Research Article - Abstract
Aim. To study the expression of angiodrastic chemokines in colorectal tumors and correlate findings with clinicopathological parameters and survival.Methods. The proangiogenic factor VEGF, the angiogenic chemokines CXCL8 and CXCL6, and the angiostatic chemokine CXCL4 were measured by ELISA in tumor and normal tissue of 35 stage II and III patients and correlated with the histopathology markers Ki67, p53, p21, bcl2, EGFR, and MLH1 and 5-year survival. The Wilcoxon and chi-square tests were used for statistical comparisons.Results. There was a significant increase of CXCL6 (p=0.005) and VEGF (p=0.003) in cancerous tissue compared to normal. Patients with lower levels of CXCL8 and CXCL4 lived significantly longer. Patients with loss of EGFR expression had higher levels of CXCL8 while p21 loss was associated with higher levels of CXCL6. Chemokine levels were not correlated with TNM or Dukes classification. Strong expression of p53 was accompanied by decreased survival.Conclusions. (1) The angiogenic factors CXCL6 and VEGF are increased in colorectal cancer tissue with no association with the clinical stage of the disease or survival. (2) However, increased levels of tissue CXCL8 and CXCL4 are associated with poor survival. (3) Strong expression of p53 is found in patients with poor survival.
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- 2018
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12. Higher free serum cortisol is associated with worse survival in acute variceal bleeding because of cirrhosis
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Konstantinos Zisimopoulos, Eleni Jelastopulu, Georgios Theocharis, Elias A. Kouroumalis, Christos Triantos, Apostolos Sapountzis, Konstantinos Thomopoulos, Dimitrios Samonakis, Maria Kalafateli, Nikolaos Papiamonis, Andrew K. Burroughs, Chryssoula Labropoulou-Karatza, Vasiliki Nikolopoulou, Venetsanea Kyriazopoulou, and Marina Michalaki
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Liver Cirrhosis ,Male ,Time Factors ,Cirrhosis ,Hydrocortisone ,Severity of Illness Index ,Gastroenterology ,Liver Function Tests ,Risk Factors ,London ,Prospective Studies ,Prospective cohort study ,Aged, 80 and over ,Greece ,biology ,Liver Neoplasms ,Area under the curve ,Middle Aged ,Prognosis ,Up-Regulation ,Area Under Curve ,Hepatocellular carcinoma ,Acute Disease ,Corticosteroid ,Female ,Gastrointestinal Hemorrhage ,Adult ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Globulin ,medicine.drug_class ,Serum Albumin, Human ,Esophageal and Gastric Varices ,Predictive Value of Tests ,Internal medicine ,Severity of illness ,medicine ,Adrenal insufficiency ,Humans ,Serum Albumin ,Aged ,Proportional Hazards Models ,Chi-Square Distribution ,Hepatology ,business.industry ,medicine.disease ,Surgery ,Logistic Models ,ROC Curve ,Multivariate Analysis ,Adrenal Cortex ,biology.protein ,Carrier Proteins ,business ,Biomarkers - Abstract
BACKGROUND AND AIMS Critical illness-related corticosteroid insufficiency has been reported in acute variceal bleeding (AVB). In cirrhosis, free serum cortisol (FC) is considered optimal to assess adrenal function. Salivary cortisol (SC) is considered a surrogate for FC. We evaluated FC and its prognostic role in AVB. METHODS Total serum cortisol, SC, cortisol-binding globulin, and FC (Coolens' formula) were evaluated in AVB (n=38) and in stable cirrhosis (CC) (n=31). A Cox proportional hazards model was evaluated for 6-week survival. RESULTS In AVB, the median FC and SC levels were higher with worse liver dysfunction [Child-Pugh (CP) A/B/C: 1.59/2.62/3.26 μg/dl, P=0.019; CPA/B/C: 0.48/0.897/1.81 μg/ml, P
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- 2014
13. Screening for Hepatopulmonary Syndrome in Cirrhotic Patients Using Technetium 99m-macroaggregated Albumin Perfusion Lung Scan (Tc-MAA): Diagnostic Approach and Clinical Correlations
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Maria Stathaki, Elias A. Kouroumalis, Dimitra Sifaki-Pistolla, Mairi Koulentaki, Dimitrios Samonakis, Sofia Koukouraki, and Maria Fragaki
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Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Population ,Perfusion scanning ,Kaplan-Meier Estimate ,030230 surgery ,Scintigraphy ,Gastroenterology ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Mass Screening ,Prospective Studies ,Hepatopulmonary syndrome ,education ,Prospective cohort study ,Radionuclide Imaging ,Technetium Tc 99m Aggregated Albumin ,education.field_of_study ,integumentary system ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Prognosis ,eye diseases ,030211 gastroenterology & hepatology ,Female ,Radiology ,Blood Gas Analysis ,Radiopharmaceuticals ,Complication ,business ,Technetium-99m ,Follow-Up Studies ,Hepatopulmonary Syndrome - Abstract
Background and aims The aims of this study were to prospectively screen cirrhotic patients with arterial blood gas test and albumin perfusion scan, identify those fulfilling the classic hepatopulmonary syndrome (HPS) criteria, correlate with clinical parameters, and evaluate the survival of patients with HPS compared with those without HPS in a genetically homogenous Cretan cirrhotic population. Materials and methods Data on consecutive 102 patients within 1 year were collected and analyzed. All patients underwent a technetium 99m-macroaggregated albumin perfusion lung scan (Tc-MAA). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA≥6% and a [P(A-a)O2]≥15 mm Hg (≥20 mm Hg for patients over >64 y). Results In 94/102 patients, complete scintigraphic data were available. In total, 24 (26%) patients fulfilled the diagnostic criteria of HPS; 95.8% of them had mild-to-moderate HPS. In 8 patients the Tc-MAA scintigraphy could not be interpreted. There was no difference in HPS between decompensated (24.6%) and compensated cirrhosis (27.3%). In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS (P=0.001, odds ratio; 95% confidence interval, 7.05; 2.27-21.87). Kaplan- Meier survival curves indicated a similar overall prognosis for patients diagnosed with HPS (P=0.105). Conclusions HPS is a frequent complication of cirrhosis. Mild-to-moderate HPS has no significant effect on survival of cirrhotic patients. The quantitative Tc-MAA test is a reliable tool for diagnosis.
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- 2017
14. Prevalence of thiopurine S-methyltransferase gene polymorphisms in patients with inflammatory bowel disease from the island of Crete, Greece
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Constantina Coucoutsi, George Emmanouil, Elias A. Kouroumalis, George N. Goulielmos, Ourania Sfakianaki, and Ioannis E. Koutroubakis
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Drug-Related Side Effects and Adverse Reactions ,Genotype ,Population ,Azathioprine ,Gastroenterology ,Inflammatory bowel disease ,Polymorphism, Single Nucleotide ,White People ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Polymorphism (computer science) ,Internal medicine ,Medicine ,Humans ,Adverse effect ,education ,Genotyping ,Aged ,Aged, 80 and over ,education.field_of_study ,Hepatology ,Thiopurine methyltransferase ,biology ,Greece ,business.industry ,Leukopenia ,Methyltransferases ,Middle Aged ,medicine.disease ,Inflammatory Bowel Diseases ,030220 oncology & carcinogenesis ,Case-Control Studies ,Mutation ,biology.protein ,030211 gastroenterology & hepatology ,Female ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
BACKGROUND There is evidence that genotyping for the thiopurine S-methyltransferase (TPMT) gene variants is useful for the prediction of response to thiopurine analogs (azathioprine and 6-mercaptopurine) in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of TPMT gene polymorphisms in a genetic homogenous population of IBD patients in Crete and to correlate the results with adverse reactions to thiopurine drugs. PATIENTS AND METHODS Genotyping for the most common TPMT variants TPMT*2, TPMT*3A, TPMT3*C, and TPMT*3B was performed using the PCR-restriction fragment length polymorphism method in 223 consecutive IBD patients and 119 age-matched and sex-matched healthy controls. The hospital medical records were reviewed for thiopurine use in these patients and related adverse events. RESULTS The prevalence of TPMT variants TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C was 1.8, 2.7, 1.3, and 1.8%, respectively. The G238C mutation was detected in four (1.8%) out of 223 patients, three (1.3%) patients were carriers of the G460A mutation, four (1.8%) of the A719G mutation, and six (2.7%) of both G460A and A719G mutations. In healthy controls, only one (0.8%) carried both the G460A and the A719G mutation, whereas TPMT*2, TPMT*3C, and TPMT*3B were not detected. None of the genotypes was homozygous. A statistically significant correlation between the presence of the G460A mutation and the development of leucopenia after the administration of thiopurines was observed (P=0.048). CONCLUSION This study showed a lower frequency of total TPMT variants and a higher frequency of TPMT*3B in Cretan IBD patients compared with other Caucasian populations. The presence of the G460A mutation is associated with the development of leukopenia.
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- 2017
15. Activin-A causes Hepatic stellate cell activation via the induction of TNFα and TGFβ in Kupffer cells
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Foteini Kiagiadaki, Elias A. Kouroumalis, Marilena Kampa, A. Voumvouraki, George Notas, and Elias Castanas
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0301 basic medicine ,Liver Cirrhosis ,Male ,endocrine system ,Alcoholic liver disease ,animal structures ,Kupffer Cells ,medicine.medical_treatment ,03 medical and health sciences ,Mice ,Non-alcoholic Fatty Liver Disease ,Transforming Growth Factor beta ,medicine ,Hepatic Stellate Cells ,Animals ,Humans ,Molecular Biology ,Aged ,Liver sinusoid ,Mice, Inbred BALB C ,biology ,Chemistry ,Tumor Necrosis Factor-alpha ,Activin receptor ,Middle Aged ,medicine.disease ,Hepatic stellate cell activation ,Fibrosis ,Activins ,030104 developmental biology ,medicine.anatomical_structure ,Cytokine ,Liver ,Case-Control Studies ,embryonic structures ,biology.protein ,Hepatic stellate cell ,Cancer research ,Molecular Medicine ,Steatohepatitis ,hormones, hormone substitutes, and hormone antagonists ,Follistatin - Abstract
Background & aims TGFβ superfamily member Activin-A is a multifunctional hormone/cytokine expressed in multiple tissues and cells, where it regulates cellular differentiation, proliferation, inflammation and tissue architecture. High activin-A levels have been reported in alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH). Our aim was to identify the cell types involved in the fibrotic processes induced by activin-A in liver and verify the liver diseases that this molecule can be found increased. Methods We studied the effect of activin-A on mouse primary Kupffer cells (KCs) and Hepatic Stellate cells (HSCs) and the levels of activin-A and its inhibitor follistatin in the serum of patients from a large panel of liver diseases. Results Activin-A is expressed by mouse hepatocytes, HSCs and Liver Sinusoid Endothelial cells but not KCs. Each cell type expresses different activin receptor combinations. HSCs are unresponsive to activin-A due to downregulation/desensitization of type-II activin receptors, while KCs respond by increasing the expression/production of TNFα και TGFβ1. In the presence of KCs or conditioned medium from activin-A treated KCs, HSCs switch to a profibrogenic phenotype, including increased collagen and αSMA expression and migratory capacity. Incubation of activin-A treated KC conditioned medium with antibodies against TNFα and TGFβ1 partially blocks its capacity to activate HSCs. Only patients with alcoholic liver diseases and NASH cirrhosis have significantly higher activin-A levels and activin-A/follistatin ratio. Conclusions Activin-A may induce fibrosis in NASH and alcoholic cirrhosis via activation of KCs to express pro-inflammatory molecules that promote HSC-dependent fibrogenesis and could be a target for future anti-fibrotic therapies.
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- 2017
16. Long-term change in incidence and risk factors of cirrhosis and hepatocellular carcinoma in Crete, Greece: a 25-year study
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Soultana Stratakou, A. Voumvouraki, Mairi Koulentaki, Aikaterini Mantaka, Spyridon A. Karageorgos, Elias A. Kouroumalis, Dimitrios Samonakis, and George Notas
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Hepatitis ,medicine.medical_specialty ,Cirrhosis ,Hepatocellular carcinoma ,business.industry ,cirrhosis ,Fatty liver ,Gastroenterology ,non-alcoholic fatty liver disease ,Hepatitis C ,Hepatitis B ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,HCV ,medicine ,Carcinoma ,Original Article ,030211 gastroenterology & hepatology ,Risk factor ,business - Abstract
Background No sequential long-term data exist for Greece on the etiological evolution and incidence of cirrhosis and hepatocellular carcinoma. Therefore, we studied their etiological evolution over a period of 25 years in the island of Crete. Methods We studied 812 cases of cirrhosis (561 male, median age 69 years) and 321 cases of hepatocellular carcinoma (234 male, median age 70 years) from the database of our Center. Cases were classified into five-year periods according to incidence and etiology (hepatitis B, hepatitis C, alcohol, alcohol plus viral, and non-alcoholic fatty liver disease). Results Overall, there was an increase in the incidence of hepatocellular carcinoma. A significant fourfold reduction in the incidence of hepatitis C-related cirrhosis was observed, which was degraded from first to third place as a risk factor for cirrhosis. Alcohol gradually became the first risk factor in cirrhosis (1990-94: 36.1%, 2010-14: 52.3%) and carcinoma, while the steepest increase in incidence of cirrhosis and carcinoma was associated with non-alcoholic fatty liver disease. Conclusions The incidence of cirrhosis remained constant over the years, but the incidence of hepatocellular carcinoma increased during the last decade. Risk factors for cirrhosis and hepatocellular carcinoma have changed over the past 25 years in Crete. The initial high hepatitis C virus association has significantly decreased, with alcohol now ranking first among risk factors. Non-alcoholic fatty liver disease is continually increasing and is a prominent risk factor for cirrhosis and hepatocellular carcinoma. Keywords Hepatocellular carcinoma, cirrhosis, non-alcoholic fatty liver disease, HCV, hepatocellular carcinoma Ann Gastroenterol 2017; 30 (3): 357-363
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- 2017
17. Octreotide modulates the effects on fibrosis of TNF-α, TGF-β and PDGF in activated rat hepatic stellate cells
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Elias A. Kouroumalis, Stefanos Klironomos, George Notas, Foteini Kiagiadaki, C. Xidakis, and Ourania Sfakianaki
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Octreotide ,Biochemistry ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Transforming Growth Factor beta ,Fibrosis ,Internal medicine ,Hepatic Stellate Cells ,medicine ,Animals ,Receptors, Somatostatin ,Sodium orthovanadate ,Cells, Cultured ,Cell Proliferation ,Platelet-Derived Growth Factor ,biology ,Tumor Necrosis Factor-alpha ,Somatostatin receptor ,Okadaic acid ,Phosphoproteins ,medicine.disease ,Rats ,Somatostatin ,Cytokine ,Liver ,chemistry ,biology.protein ,Hepatic stellate cell ,Cancer research ,Collagen ,Protein Tyrosine Phosphatases ,Protein Processing, Post-Translational ,Platelet-derived growth factor receptor - Abstract
Background and aims Somatostatin and its analogs may influence hepatic fibrosis interfering through several mechanisms. The aim of this study was to investigate the effect of octreotide on cytokine activated hepatic stellate cells (HSC). Methods Primary HSCs were isolated from rats and were cultured on plastic for activation. Expression of somatostatin receptors (SSTR) was investigated in cultured HSCs by immunofluorescence and western blot. The effect of octreotide on cellular proliferation was studied with the MTT assay and western blot for α1-procollagen (α1-PROC) production in TNFα, TGF-β1 or PDGF treated HSCs. Phosphotyrosine (PTP) and phosphoserine–phosphothreonine (STP) phosphatases inhibition was performed with sodium orthovanadate and okadaic acid respectively. Results Activated HSC express SSTR subtypes 1, 2A, 2B, 3 and 4 and their expression is enhanced by further HSC activation. Octreotide did not have an effect on HSC proliferation but inhibited plastic induced α1-PROC production. Interestingly, it enhanced PDGF-induced HSC proliferation but inhibited PDGF and TGFβ1 dependent expression of α1-PROC, while an opposite effect was observed in TNFα-induced cell proliferation and collagen production. PTP inhibition reversed the inhibitory effect of octreotide on α1-PROC, but potentiated its effect on PDGF and TGFβ1 dependent α1-PROC production. Finally, STP inhibition profoundly inhibited α1-PROC expression in all cases suggesting that both STP and PTP phosphatases are important regulators of pro-fibrotic mechanisms. Conclusions The net effect of octreotide on HSCs and therefore liver fibrosis is subject to the cytokine microenvironment of these cells. This effect is modulated by PTPs and STPs inhibition. Especially in the case of STPs their profibrotic effects could be an interesting new therapeutic target in liver fibrosis.
- Published
- 2014
18. Epidemiology and molecular analysis of hepatitis A, B and C in a semi-urban and rural area of Crete
- Author
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I. Drositis, A. Bertsias, Elias A. Kouroumalis, and Christos Lionis
- Subjects
Adult ,Male ,Rural Population ,Hepatitis B virus ,HBsAg ,Adolescent ,Urban Population ,Hepatitis C virus ,Population ,Hepacivirus ,medicine.disease_cause ,Young Adult ,Age Distribution ,Seroepidemiologic Studies ,Prevalence ,Internal Medicine ,medicine ,Humans ,Hepatitis B Antibodies ,education ,Aged ,Molecular Epidemiology ,education.field_of_study ,Hepatitis B Surface Antigens ,Greece ,business.industry ,Hepatitis A ,Hepatitis C ,Hepatitis C Antibodies ,Middle Aged ,Hepatitis B ,medicine.disease ,Virology ,DNA, Viral ,RNA, Viral ,Female ,business ,Viral hepatitis ,Demography - Abstract
Aim An observational seroepidemiological study was carried out in a well-defined primary-care district on the island of Crete in order to determine the recent endemicity of viral hepatitis in Cretan-population. Setting and participants The setting consisted of a semi-urban group and a remote & rural group. Serum samples were collected from 876 subjects (437 males, 439 females) aged 15 years or above. Subjects were randomly selected from the permanent population of the area that consisted of 5705 individuals. The aim was to measure the prevalence of selected viral-hepatitis markers. Results Hepatitis B surface-antigen (HBsAg) was found positive in twenty-nine individuals, (3.3%). Antibodies to hepatitis B virus core-antigen (HBcAb) were detected in 287 subjects (32.8%) and antibodies to hepatitis C virus (anti-HCV) were detected in nineteen subjects (2.2%). Seropositivities for the semi-urban group were: 3.4%, 19.1%, 2.1% and 3.2%, 48.8%, 2.2% in remote & rural group respectively. Virtually, all subjects > 45 years old were seropositive for antibodies to hepatitis A, whereas approximately 80% of those in the 15–44 age-group were found to be seropositive. Conclusion A threefold increase in the HBV exposure and carrier proportion was found in Cretan native-population and in rural-areas compared to older studies carried out in other rural-populations of the island. It is still unknown whether the recent economic crisis or the demographic changes in Cretan-population contributed to these findings. HCV endemicity remains relatively constant, however an alteration of hepatitis C genotypes was observed. Exposure to HAV was found to be higher in remote and rural areas compared to semi-urban areas.
- Published
- 2013
19. CXCR3 axis in patients with primary biliary cirrhosis: a possible novel mechanism of the effect of ursodeoxycholic acid
- Author
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Leonidas A. Bourikas, M Koulentaki, Helen A. Papadaki, Pinelopi Manousou, George Kolios, George Notas, Katerina Pyrovolaki, A. Voumvouraki, Elias A. Kouroumalis, and Ioannis Drygiannakis
- Subjects
Adult ,Male ,Cholagogues and Choleretics ,medicine.medical_specialty ,Receptors, CXCR3 ,Biopsy ,CD3 ,Immunology ,Gene Expression ,CXCR3 ,Chemokine CXCL9 ,Primary biliary cirrhosis ,stomatognathic system ,Internal medicine ,medicine ,Humans ,Protein Isoforms ,Immunology and Allergy ,CXCL10 ,CXCL11 ,RNA, Messenger ,skin and connective tissue diseases ,medicine.diagnostic_test ,biology ,Liver Cirrhosis, Biliary ,business.industry ,Chemotaxis ,Ursodeoxycholic Acid ,Original Articles ,Middle Aged ,medicine.disease ,Ursodeoxycholic acid ,Chemokine CXCL11 ,Chemokine CXCL10 ,stomatognathic diseases ,Endocrinology ,Liver ,Case-Control Studies ,Liver biopsy ,Leukocytes, Mononuclear ,biology.protein ,CXCL9 ,Female ,business ,medicine.drug - Abstract
Summary The CXC chemokines, monokine induced by interferon (IFN)-gamma (MIG) (CXCL9), IFN-gamma-induced protein 10 (IP-10) (CXCL10) and IFN-inducible T cell alpha chemoattractant (I-TAC) (CXCL11), are known to attract CXCR3- (CXCR3A and CXCR3B) T lymphocytes. We investigated MIG, IP-10 and I-TAC mRNAs expression by semi-quantitative multiplex reverse transcription–polymerase chain reaction (RT–PCR) in liver biopsies obtained from patients with a first diagnosis of primary biliary cirrhosis [(PBC) = 20] compared to patients with normal liver biopsy [normal controls (NCs) = 20]. Chemokine production was assessed by enzyme-linked immunosorbent assay (ELISA) in serum. Measurements were repeated 6 months after ursodeoxycholic acid (UDCA) treatment in PBC patients. CXCR3A and CXCR3B mRNAs expression was examined in immunomagnetically sorted CD3+ peripheral blood lymphocytes (PBL) pre- and post-treatment by RT–PCR. Flow cytometry was used to evaluate the expression of CXCR3+ PBLs of NCs and PBC patients. A marked mRNA expression of MIG and IP-10 was found in PBC patients. I-TAC mRNA was not detected. In serum of PBC patients there was a significant increase of MIG and IP-10 compared to NCs. Interestingly, there was a significant reduction of these proteins in patients' serum after UDCA treatment. I-TAC was not statistically different between groups. CXCR3A mRNA expression was found in PBLs from PBC patients as well as in NCs. CXCR3B mRNA was expressed in four of 20 (19%) NCs and 20 of 20 PBC patients. Flow cytometry revealed a significantly lower CXCR3 expression in NCs (13·5%) than in PBC (37·2%), which was reduced (28·1%, P
- Published
- 2013
20. Genetic variants associated with susceptibility to mother-to-child transmission of hepatitis B virus
- Author
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Virginia Chatzidaki, Helen Dimitriou, Elias A. Kouroumalis, Emmanouil Galanakis, and Despoina M. Choumerianou
- Subjects
Male ,Hepatitis B virus ,Adolescent ,Genotype ,TaqI ,medicine.disease_cause ,Mannose-Binding Lectin ,Polymerase Chain Reaction ,Calcitriol receptor ,chemistry.chemical_compound ,Hepatitis B, Chronic ,Gene Frequency ,Vitamin D and neurology ,Humans ,Medicine ,Allele ,Child ,Allele frequency ,Polymorphism, Genetic ,Hepatology ,Tumor Necrosis Factor-alpha ,business.industry ,Gastroenterology ,Infant ,Chronic infection ,Haplotypes ,chemistry ,Child, Preschool ,Immunology ,Disease Progression ,Receptors, Calcitriol ,Female ,business - Abstract
Objective The mechanisms of immune tolerance to hepatitis B virus (HBV) in children infected perinatally or early in infancy still remain unclarified. We aimed to study the genetic variants of immune factors implicated in viral–host interaction in children who were born to HBV-positive mothers and who had different clinical outcome. Methods Mannose-binding lectin gene (mbl2) codon 54, codon 57, and promoter 221 variants, tumor necrosis factor α (TNF-α) 308G/A, and vitamin D receptor (VDR) ApaI and TaqI genotypes were analyzed in three groups of children born to HBV-positive mothers: children with chronic infection (n=33), those with resolved infection (n=36), and those naive for HBV (n=33). Results TNF-α −308G allele frequency was found to be increased in children with chronic infection compared with children who were not affected by HBV [risk ratio (RR) 1.12, 95% confidence interval (CI) 1.0–1.25; P=0.050]. The VDR ApaI A allele tended to be more frequent in children with chronic infection than in those with resolved HBV infection (RR 1.27, 95% CI 0.95–1.67; P=0.071). The VDR ApaI α allele in ApaI and TaqI joint haplotype αT was more frequent in children with resolved infection than in those with chronic infection (RR 1.74, 95% CI 0.97–3.13; P=0.049). Conclusion Our results suggest that TNF-α and vitamin D pathways may be involved in the susceptibility to and outcome of HBV infection acquired early in life.
- Published
- 2012
21. NOD2 insertion mutation in a Cretan Crohn's disease population
- Author
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Ioannis E. Koutroubakis, M. Roussomoustakaki, Stavroula Baritaki, Em Manouel Vardas, Elias A. Kouroumalis, Philippos Dimoulios, George Koutsoudakis, and Elias Krambovitis
- Subjects
Genetics ,education.field_of_study ,Crohn's disease ,Hepatology ,Crohn disease ,business.industry ,Population ,Gastroenterology ,medicine.disease ,Carrier protein ,NOD2 ,Mutation (genetic algorithm) ,medicine ,Insertion ,education ,business - Published
- 2016
22. Systemic treatment for hepatocellular carcinoma: Still unmet expectations
- Author
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Dimitrios Samonakis and Elias A. Kouroumalis
- Subjects
Oncology ,Genome instability ,medicine.medical_specialty ,Cell type ,Cirrhosis ,Hepatocellular carcinoma ,medicine.medical_treatment ,Clinical settings ,Review ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Chemotherapy ,Hepatology ,business.industry ,Systemic chemotherapy ,Advanced stage ,Systemic ,medicine.disease ,Prognosis ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business - Abstract
Many patients with hepatocellular carcinoma (HCC) are diagnosed in an advanced stage, so they cannot be offered the option of curative treatments. The results of systemic chemotherapy are unsatisfactory and this has led to molecular targeted approaches. HCC develops in chronically damaged tissue due to cirrhosis in most patients. Several different cell types and molecules constitute a unique microenvironment in the liver, which has significant implications in tumor development and invasion. This, together with genome instability, contributes to a significant heterogeneity which is further enhanced by the molecular differences of the underlying causes. New classifications based on genetic characteristics of the tissue microenvironment have been proposed and key carcinogenic signaling pathways have been described. Tumor and adjacent tissue profiling seem biologically promising, but have not yet been translated into clinical settings. The encouraging first results with molecular - genetic signatures should be validated and clinically applicable. A more personalized approach to modern management of HCC is urgently needed.
- Published
- 2016
23. Increased serum activin-A differentiates alcoholic from cirrhosis of other aetiologies
- Author
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Elias A. Kouroumalis, George Notas, A. Voumvouraki, Stefanos Klironomos, M Georgiadou, and Mairi Koulentaki
- Subjects
medicine.medical_specialty ,Alcoholic liver disease ,Cirrhosis ,business.industry ,Clinical Biochemistry ,General Medicine ,medicine.disease ,Biochemistry ,Gastroenterology ,Pathophysiology ,Primary biliary cirrhosis ,medicine.anatomical_structure ,Fibrosis ,Hepatocellular carcinoma ,Internal medicine ,Medicine ,Alcoholic fatty liver ,business ,Vein - Abstract
Eur J Clin Invest 2012 Abstract Background Activin-A is a molecule of the TGF superfamily, implicated in liver fibrosis, regeneration and stem cell differentiation. However, data on activins in liver diseases are few. We therefore studied serum levels of activin-A in chronic liver diseases. To identify the origin of activin-A, levels in the hepatic vein were also estimated. Materials and methods Nineteen controls and 162 patients participated in the study: 39 with hepatocellular carcinoma (HCC: 19 viral associated and 20 alcohol associated), 18 with chronic hepatitis C (CHC), 47 with primary biliary cirrhosis (26 PBC stage I–II and 21 stage IV), 22 with alcoholic cirrhosis (AC, hepatic vein blood available in 16), 20 with HCV cirrhosis (hepatic vein blood available in 18) and 16 patients with alcoholic fatty liver with mild to moderate fibrosis but no cirrhosis. Results Activin-A levels were significantly increased (P
- Published
- 2012
24. Acute TIPS occlusion due to iatrogenic arteriovenous shunt in a cirrhotic patient with total portal vein thrombosis
- Author
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Dimitrios Samonakis, Emmanuel Digenakis, Dimitrios Tsetis, Elias Kehagias, Elias A. Kouroumalis, and Adam Hatzidakis
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Portal venous pressure ,Stent ,Case Report ,General Medicine ,medicine.disease ,Surgery ,Portal vein thrombosis ,Shunt (medical) ,Melena ,Ascites ,medicine ,Portal hypertension ,Radiology ,medicine.symptom ,business ,Transjugular intrahepatic portosystemic shunt - Abstract
A 69-year-old man with portal hypertension was admitted with decompensated alcoholic cirrhosis and diuretic resistant ascites. Ultrasound revealed partial portal thrombosis. Due to diuretic intolerance, transjugular intrahepatic portosystemic shunt (TIPS) was decided during which a hepatic arterial branch was inadvertently catheterized. Finally, TIPS was created, but the patient continued gaining weight. Color-Doppler ultrasonography (CDUS) showed upper stent part patency with absence of flow in lower stent portion. Twenty-five days later, the patient presented melena. Endoscopy revealed blood emerging from the Vater papilla. Hepatic angiography revealed arteriovenous shunt between a hepatic arterial branch and the proximal part of the TIPS shunt. Covered stent placement restored sufficient TIPS flow. The patient deteriorated and died 1 month later. We found out that our major technical drawback was that we did not inject a small amount of contrast after puncturing the supposed portal vein, in order to confirm correct position of the needle.
- Published
- 2015
25. Assessment of a postoperative anastomotic stricture following correction surgery of a type IVa choledochal cyst using Gd-EOB-DTPA-enhanced magnetic resonance cholangiography
- Author
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Apostolos H. Karantanas, Evangelos Perdikakis, Evangelia G. Chryssou, Elias A. Kouroumalis, and Mairi Koulentaki
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Bile duct ,Gastroenterology ,Magnetic resonance imaging ,General Medicine ,Anastomosis ,Hepatology ,medicine.disease ,Colorectal surgery ,Surgery ,Cholangiography ,medicine.anatomical_structure ,Internal medicine ,medicine ,Choledochal cysts ,Radiology ,business ,Abdominal surgery - Abstract
Choledochal cyst is a relatively uncommon disease which is characterized by congenital dilatation of the intra and/or extrahepatic part of the biliary tree. Type IVa choledochal cysts are managed surgically through total excision of the entire extrahepatic part of the abnormal bile ducts and a simultaneous hepaticoenterostomy. Postoperative anastomotic stricture after excision of choledochal cysts and hepaticojejunostomy is a well-known late complication. We report a case of a 17-year-old female in whom gadoxetic acid-enhanced magnetic resonance cholangiography assisted in the evaluation of a biliary stricture following bile duct procedures after choledochal cyst correction surgery.
- Published
- 2011
26. Serum hepcidin and prohepcidin concentrations in inflammatory bowel disease
- Author
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Aekaterini Sfiridaki, Pantelis Oustamanolakis, Niki Malliaraki, Ippokratis Messaritakis, Elias A. Kouroumalis, and Ioannis E. Koutroubakis
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Anemia ,Iron ,Prohormone ,Anti-Inflammatory Agents ,digestive system ,Inflammatory bowel disease ,Young Adult ,Gastrointestinal Agents ,Hepcidins ,Hepcidin ,hemic and lymphatic diseases ,Azathioprine ,medicine ,Humans ,Enzyme Inhibitors ,Protein Precursors ,Aged ,Glucosamine ,Crohn's disease ,Hepatology ,biology ,business.industry ,Smoking ,Gastroenterology ,nutritional and metabolic diseases ,Iron deficiency ,Middle Aged ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Sulfasalazine ,Drug Combinations ,C-Reactive Protein ,Cross-Sectional Studies ,Methotrexate ,Iron-deficiency anemia ,Immunology ,biology.protein ,Female ,business ,Antimicrobial Cationic Peptides ,medicine.drug - Abstract
Anemia is an important complication of inflammatory bowel disease (IBD). Recent data suggest that hepcidin is a major mediator of anemia with a central role in iron homeostasis and metabolism. The aim of this study was to evaluate the serum levels of hepcidin and its prohormone, prohepcidin, in patients with IBD in comparison with healthy controls.One hundred patients with IBD [49 ulcerative colitis (UC), 51 Crohn's disease (CD)] and 102 healthy controls were enrolled. Serum hepcidin and prohepcidin levels were measured by commercially available enzyme-linked immunosorbent assays kits. Their relationship with clinical and laboratory parameters of UC and CD was assessed.Median hepcidin levels were significantly higher in both patients with UC and patients with CD compared with healthy controls (P0.0001). Median prohepcidin levels were significantly lower in patients with IBD compared with healthy controls (P = 0.03). In the univariate analysis, serum hepcidin was significantly negatively correlated (r = -0.36, P = 0.0003), whereas serum prohepcidin was positively correlated (r = 0.65, P0.0001) with the hemoglobin levels. Significant correlations of both hepcidin (r = 0.34, P = 0.0007) and prohepcidin (r = -0.21, P = 0.04) with ferritin levels were found in patients with IBD. Serum hepcidin was also correlated with disease activity (for UC, r = 0.36, P = 0.009) and C-reactive protein (r = 0.29, P = 0.004). After multivariate analysis serum hepcidin levels remained significantly correlated with ferritin (P = 0.0008) and disease activity (for UC, P = 0.004).Serum hepcidin and prohepcidin levels are significantly altered in patients with IBD compared with healthy controls. This finding suggests a substantial role of these two hormones in the development of anemia in IBD.
- Published
- 2011
27. Serum surrogate markers of liver fibrosis in primary biliary cirrhosis
- Author
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Ourania Sfakianaki, George Notas, Mairi Koulentaki, Elias A. Kouroumalis, and Argiro Voumvouraki
- Subjects
Collagen Type IV ,Leptin ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Disease ,Sensitivity and Specificity ,Gastroenterology ,Diagnosis, Differential ,Primary biliary cirrhosis ,Adjuvants, Immunologic ,Predictive Value of Tests ,Fibrosis ,Laminin ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hyaluronic Acid ,Vein ,Aged ,biology ,Liver Cirrhosis, Biliary ,business.industry ,Liver Neoplasms ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,digestive system diseases ,Early Diagnosis ,medicine.anatomical_structure ,Case-Control Studies ,Hepatocellular carcinoma ,biology.protein ,Female ,business ,Algorithms ,Biomarkers - Abstract
Hyaluronan, leptin, laminin and collagen IV have been used extensively for the assessment of liver fibrosis. The aim of this study was to assay these markers in the peripheral and hepatic vein blood of primary biliary cirrhosis (PBC) patients and to study their ability to discriminate early from advanced disease.Sera from 62 PBC patients were compared to 60 controls, 44 chronic Hepatitis C, 38 hepatocellular carcinoma and 34 viral cirrhosis patients. Serum from the hepatic vein of 15 cirrhotic PBC patients and 17 patients with viral cirrhosis was also assayed.All disease groups had significantly increased levels of hyaluronan and collagen IV, compared to controls, while laminin was significantly increased only in viral cirrhosis. Hyaluronan levels were statistically different between early (54.5 ng/ml; 95%CI 27.3-426.9) and late PBC (154.5 ng/ml; 95%CI 55.3-764.4, p0.05). The area under the curve (AUC) for the identification of late PBC was 0.74 for hyaluronan, 0.63 for leptin, 0.59 for laminin and 0.70 for collagen IV. Hyaluronan had high sensitivity and NPV in identifying late stages of PBC (96% and 90%, respectively). Short term UDCA had no effect on these markers.No single measurement can differentiate between advanced and early fibrosis in PBC. However serum hyaluronan is a promising single serum marker for longitudinal studies in PBC.
- Published
- 2011
28. A concentration-dependent effect of ursodeoxycholate on apoptosis and caspases activities of HepG2 hepatocellular carcinoma cells
- Author
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Antonis G. Batistakis, Ioannis Drygiannakis, George Kolios, Elias A. Kouroumalis, and Nikos J. Tsagarakis
- Subjects
Programmed cell death ,Carcinoma, Hepatocellular ,Apoptosis ,DNA Fragmentation ,Ligands ,medicine ,Humans ,Annexin A5 ,Caspase ,Cell Proliferation ,Pharmacology ,Dose-Response Relationship, Drug ,biology ,Tumor Necrosis Factor-alpha ,Cell growth ,Ursodeoxycholic Acid ,Ursodeoxycholate ,Hep G2 Cells ,Ursodeoxycholic acid ,Biochemistry ,Organ Specificity ,Caspases ,Cancer research ,biology.protein ,DNA fragmentation ,Signal Transduction ,medicine.drug - Abstract
Clinical observations suggest that ursodeoxycholate (UDCA) may protect from hepatocellular carcinoma in cirrhotic patients. Increased apoptosis of malignant cells is a candidate mechanism. Decreased apoptosis of cholangiocytes is proposed as a mechanism for the favourable effect of UDCA in primary biliary cirrhosis. We therefore studied the effects of different concentrations of UDCA on HepG2 cell proliferation, apoptosis and caspases activities. Apoptotic features and activities of the effector or initiator caspases-8, -9, -3 and -2 after treatment of HepG2 cells with different concentrations of UDCA alone or in combination with TNF-alpha were examined. Apoptosis was detected by DNA fragmentation and flow cytometric determination of apoptotic cells with Annexin-V/PI. UDCA significantly inhibits cell proliferation only at high concentrations, but increases apoptosis at low concentrations and protects from apoptosis at higher concentrations. TNF-alpha induced DNA fragmentation is potentiated by UDCA, but flow cytometry indicates protection from early apoptosis and increase in cell survival by low and intermediate UDCA concentrations. UDCA differentially activates initiator and effector caspases in different concentrations. These data demonstrate that the effect of UDCA on caspase activation and apoptosis of HepG2 cells is concentration-dependent and activation of the caspase cascade is not always translated into increased apoptosis. Serum levels of UDCA should be possibly monitored and dosage of the drug adjusted according to the required effect.
- Published
- 2010
29. Somatostatin in hepatocellular carcinoma: experimental and therapeutic implications
- Author
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George Notas, Demetrius Samonakis, and Elias A. Kouroumalis
- Subjects
Somatostatin ,Oncology ,Hepatology ,Somatostatin receptor ,business.industry ,Hepatocellular carcinoma ,medicine ,Cancer research ,medicine.disease ,business - Published
- 2018
30. Percutaneous Palliation of Pancreatic Head Cancer: Randomized Comparison of ePTFE/FEP–Covered Versus Uncovered Nitinol Biliary Stents
- Author
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Dimitrios Tsetis, Elias A. Kouroumalis, Ioannis A. Mouzas, Fabrizio Fanelli, Mario Bezzi, Roberto Pasariello, Miltiadis Krokidis, Adam Hatzidakis, and Gianluigi Orgera
- Subjects
Adult ,Male ,medicine.medical_specialty ,Percutaneous ,Prosthesis Design ,law.invention ,Prosthesis Implantation ,Coated Materials, Biocompatible ,Randomized controlled trial ,law ,Pancreatic cancer ,Alloys ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,cardiovascular diseases ,Prospective cohort study ,Pancreas ,Polytetrafluoroethylene ,Survival analysis ,Aged ,biliary stents ,biliary drainage ,pancreatic cancer ,bile duct obstruction ,percutaneous interventions ,eptfe/fep ,covered metallic stents ,malignant jaundice ,bile duct stent ,pancreatic neoplasms ,business.industry ,Palliative Care ,Middle Aged ,Jaundice ,equipment and supplies ,medicine.disease ,Survival Analysis ,Surgery ,Pancreatic Neoplasms ,Biliary Tract Surgical Procedures ,Jaundice, Obstructive ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,Female ,Stents ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Pancreatic head cancer - Abstract
The purpose of this study was to compare the clinical effectiveness of expanded polytetrafluoroethylene/fluorinated-ethylene-propylene (ePTFE/FEP)-covered stents with that of uncovered nitinol stents for the palliation of malignant jaundice caused by inoperable pancreatic head cancer. Eighty patients were enrolled in a prospective randomized study. Bare nitinol stents were used in half of the patients, and ePTFE/FEP-covered stents were used in the remaining patients. Patency, survival, complications, and mean cost were calculated in both groups. Mean patency was 166.0 ± 13.11 days for the bare-stent group and 234.0 ± 20.87 days for the covered-stent group (p = 0.007). Primary patency rates at 3, 6, and 12 months were 77.5, 69.8, and 69.8% for the bare-stent group and 97.5, 92.2, and 87.6% for the covered-stent group, respectively. Mean secondary patency was 123.7 ± 22.5 days for the bare-stent group and 130.3 ± 21.4 days for the covered-stent group. Tumour ingrowth occurred exclusively in the bare-stent group in 27.5% of cases (p = 0.002). Median survival was 203.2 ± 11.8 days for the bare-stent group and 247.0 ± 20 days for the covered-stent group (p = 0.06). Complications and mean cost were similar in both groups. Regarding primary patency and ingrowth rate, ePTFE/FEP-covered stents have shown to be significantly superior to bare nitinol stents for the palliation of malignant jaundice caused by inoperable pancreatic head cancer and pose comparable cost and complications. Use of a covered stent does not significantly influence overall survival rate; nevertheless, the covered endoprosthesis seems to offer result in fewer reinterventions and better quality of patient life.
- Published
- 2010
31. Apoptosis and Cell Proliferation Correlated with Tumor Grade in Patients with Ampullary Carcinoma
- Author
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Efstathios N. Stathopoulos, Odysseas Zoras, Elias A. Kouroumalis, Michael Papadakis, Alexandra Kalogeraki, and Maria Tzardi
- Subjects
Male ,Ampulla of Vater ,Programmed cell death ,Pathology ,medicine.medical_specialty ,Histology ,Common Bile Duct Neoplasms ,Apoptosis ,DNA Fragmentation ,Adenocarcinoma ,Giemsa stain ,Pathology and Forensic Medicine ,In Situ Nick-End Labeling ,Cytology ,medicine ,Carcinoma ,Humans ,Aged ,Cell Proliferation ,Neoplasm Staging ,Aged, 80 and over ,Endoscopic retrograde cholangiopancreatography ,TUNEL assay ,medicine.diagnostic_test ,business.industry ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Antibodies, Antinuclear ,Female ,business - Abstract
Objective To evaluate apoptosis and cell proliferation on cytologic specimens (smears) from endoscopic retrograde cholangiopancreatography in patients with ampulary carcinoma and to correlate that relationship with the grade of the tumors. Study design Forty patients (23 males and 17 females) aged 45-81 who underwent endoscopic retrograde cholangiopancreatography were diagnosed by cytology as having ampullary adenocarcinoma and the diagnoses were confirmed histologically after an operation. All smears were stained using Papanicolaou and Giemsa stain. Apoptosis was assessed using terminal digoxigenin-labeled dUTP nick-end labeling (TUNEL assay) and cell proliferation using MIB-1 monoclonal antibody by the alkaline phosphatase method. Results The TUNEL indices were 0.4 +/- 0.07, 0.91 +/- 0.33 and 3.1 +/- 0.9 in well, moderate and poorly differentiated ampullary carcinoma, respectively. The differences in both TUNEL and MIB-1 labeling indices were statistically significant between well, moderately and poorly differentiated ampullary carcinoma, and a positive correlation was found between TUNEL and the MIB-1 indices. Conclusion Apoptosis (cell death) and cell proliferation increase as the grade of the differentiation decreases in ampullary carcinoma, suggesting a rapid turnover of the tumor cells with lower grates of differentiation, and apoptosis may play an important role in the growth of the tumors in patients with ampullary carcinomas.
- Published
- 2010
32. Ciprofloxacin decreases survival in HT-29 cells via the induction of TGF-β1 secretion and enhances the anti-proliferative effect of 5-fluorouracil
- Author
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Iordanis Pelagiadis, Ioannis Drygiannakis, Elias A. Kouroumalis, Stefanos Klironomos, Leonidas A. Bourikas, Vassilis Valatas, Pinelopi Manousou, Ioannis A. Mouzas, George Notas, and George Kolios
- Subjects
Pharmacology ,medicine.medical_specialty ,Necrosis ,Cell growth ,business.industry ,Cell cycle ,HT29 Cells ,Endocrinology ,Caco-2 ,Cell culture ,Apoptosis ,Internal medicine ,medicine ,Cancer research ,medicine.symptom ,business ,Antibacterial agent - Abstract
Background and purpose: Fluoroquinolones are potent anti-microbial agents with multiple effects on host cells and tissues. Previous studies have highlighted their pro-apoptotic effect on human cancer cells and an immunoregulatory role in animal models of inflammatory bowel disease. We examined the effect of ciprofloxacin on proliferation, cell cycle and apoptosis of HT-29 cells, a human colonic epithelial cell line sensitive to transforming growth factor (TGF)-β1-mediated growth inhibition and its role in TGF-β1 production. We also examined the effect of ciprofloxacin on proliferation of HT-29 cells in combination with 5-fluorouracil (5-FU), a well-established pro-apoptotic agent. Experimental approach: Using subconfluent cultures of HT-29 and Caco-2 cells, we studied the effect of ciprofloxacin, TGF-β1 and 5-FU on proliferation, apoptosis, necrosis and cell cycle. The effect of ciprofloxacin on TGF-β1 mRNA expression and production was studied in RNA extracts and cell culture supernatants respectively, using confluent cultures. Key results: Ciprofloxacin decreased proliferation of HT-29 cells in a concentration- and time-dependent manner. This was mediated by accumulation of HT-29 cells into the S-phase but without any effect on apoptosis or necrosis. Additionally, ciprofloxacin enhanced the antiproliferative effect of 5-FU. Interestingly, ciprofloxacin was found to up-regulate TGF-β1 production by HT-29 cells and its anti-proliferative effect was abolished when TGF-β1 was blocked. Confirming this mechanism further, ciprofloxacin had no effect on Caco-2, a human colonic epithelial cell line that lacks functional TGF-β1 receptors. Conclusions and implications: We demonstrate a novel anti-proliferative and immunoregulatory effect of ciprofloxacin on human intestinal epithelial cells mediated via TGF-β1.
- Published
- 2009
33. Expression of a splice variant of CXCR3 in Crohn's disease patients; indication for a lymphocyte-epithelial cell interaction
- Author
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Leonidas A. Bourikas, George Kolios, Helen A. Papadaki, Pinelopi Manousou, Ioannis Drygiannakis, Elias A. Kouroumalis, and Katerina Pyrovolaki
- Subjects
Adult ,Male ,Chemokine ,Receptors, CXCR3 ,CD3 Complex ,Colon ,T-Lymphocytes ,Receptor expression ,CD3 ,Lymphocyte ,CXCR3 ,Jurkat cells ,Proinflammatory cytokine ,Jurkat Cells ,Chemokine receptor ,Crohn Disease ,Humans ,Protein Isoforms ,Medicine ,RNA, Messenger ,Intestinal Mucosa ,Hepatology ,biology ,business.industry ,Chemotaxis ,Gastroenterology ,Epithelial Cells ,hemic and immune systems ,Colonoscopy ,Flow Cytometry ,Molecular biology ,medicine.anatomical_structure ,Case-Control Studies ,Immunology ,biology.protein ,Cytokines ,Colitis, Ulcerative ,Female ,Caco-2 Cells ,Chemokines ,Inflammation Mediators ,business ,HT29 Cells - Abstract
Background and Aim: T-lymphocyte migration is implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). CXC chemokines MIG, IP-10, and I-TAC act by binding to CXCR3 receptor on T-lymphocytes. We investigated the role of these chemokines and their receptor in patients with UC, CD, and normal controls (NC). Methods: Chemokine expression and serum levels were examined in colonic biopsies from patients and NC using reverse transcription–polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. HT-29 and Caco2 colonic epithelial cells were studied following in vitro stimulation with proinflammatory (Th1) and Th2-derived cytokines. CXCR3 receptor expression was assessed in CD3+ peripheral blood lymphocytes (PBL) from patients and NC and in stimulated Jurkat leukaemia cells, using RT-PCR and flow cytometry. Results: Full size CXCR3 mRNA (FS) expression was found in CD3+ PBL from controls and UC, but not from CD patients. In contrast, CD3+ PBL from CD patients showed a marked mRNA expression of the spliced variant CXCR3 (TV). This finding explains the high expression of CXCR3 on CD3+ PBL from CD patients in flow cytometry. Increased chemokine expression and production was found in colonic biopsies and serum from CD compared to UC patients and controls. Stimulation of epithelial cells with proinflammatory cytokines significantly induced chemokine production. The addition of Th2 cytokines had an inhibitory effect. Stimulation of Jurkat cells with cytokines and supernatant conditioned media from epithelial cells induced CXCR3TV expression. Conclusions: These data demonstrate that PBL from CD patients express a spliced variant of the CXCR3 receptor and suggest a role for the colonic epithelial cells in T-lymphocyte migration in intestinal inflammation.
- Published
- 2008
34. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels in inflammatory bowel disease
- Author
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Aekaterini Sfiridaki, Georgia Tsiolakidou, Ioannis E. Koutroubakis, Constantina Coucoutsi, Angeliki Theodoropoulou, and Elias A. Kouroumalis
- Subjects
Adult ,Male ,Carboxypeptidase B2 ,medicine.medical_treatment ,Pharmacology ,Inflammatory bowel disease ,chemistry.chemical_compound ,Thrombin ,Crohn Disease ,Plasminogen Activator Inhibitor 1 ,Fibrinolysis ,medicine ,Humans ,Crohn's disease ,Hepatology ,business.industry ,Vascular disease ,Gastroenterology ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,chemistry ,Plasminogen activator inhibitor-1 ,Immunology ,Colitis, Ulcerative ,Female ,business ,Plasminogen activator ,Biomarkers ,medicine.drug - Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of thromboembolic events. Imbalance of fibrinolysis has been suggested as one of the possible pathogenetic mechanisms. As plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) are inhibitors of fibrinolysis, we studied TAFI as well as PAI-1 plasma levels in IBD patients compared with healthy controls.A total of 132 IBD patients [68 ulcerative colitis (UC) and 64 Crohn's disease (CD)] and 50 healthy controls were enrolled. PAI-1 and TAFI plasma levels were assessed by commercially available enzyme-linked immunosorbent assay kits. Their relationship with clinical parameters of UC and CD was assessed.Mean plasma PAI-1 levels were significantly higher in both UC patients (3.9+/-1.3 IU/ml) and CD patients (4.0+/-1.5 IU/ml) compared with healthy controls (3.1+/-1.1 IU/ml) (P=0.01). On the other hand, mean plasma TAFI levels were significantly lower in both UC patients (14.7+/-3.1 microg/ml) and CD patients (13.3+/-3.4 microg/ml) compared with healthy controls (17.4+/-3.0 microg/ml) (P0.0001). Patients with active disease had significantly higher PAI-1 levels compared with patients with inactive disease for both diseases (P=0.03 and P=0.01, respectively). No significant association between plasma TAFI levels and disease activity was also found. Plasma TAFI levels were significantly lower in patients with ileal CD compared with patients with colonic CD.PAI-1 plasma levels are increased whereas TAFI levels are decreased in IBD patients. These results suggest an imbalance of fibrinolysis in IBD.
- Published
- 2008
35. Levels of circulating endothelin-1 and nitrates/nitrites in patients with virus-related hepatocellular carcinoma
- Author
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Elias A. Kouroumalis, A. Kouroumalis, George Notas, C. Xidakis, and V. Valatas
- Subjects
chemistry.chemical_compound ,Infectious Diseases ,Hepatology ,chemistry ,Virology ,Hepatocellular carcinoma ,medicine ,Cancer research ,In patient ,medicine.disease ,Endothelin 1 ,Virus ,Nitric oxide - Published
- 2008
36. Nitric oxide and MCP-1 regulation in LPS activated rat Kupffer cells
- Author
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Pinelopi Manousou, C. Xidakis, George Notas, George Kolios, Vassilis Valatas, and Elias A. Kouroumalis
- Subjects
Lipopolysaccharides ,Male ,medicine.medical_specialty ,Kupffer Cells ,Phosphodiesterase Inhibitors ,Clinical chemistry ,Clinical Biochemistry ,Biology ,Nitric Oxide ,Nitric oxide ,Rats, Sprague-Dawley ,Wortmannin ,Phosphatidylinositol 3-Kinases ,Basal (phylogenetics) ,chemistry.chemical_compound ,Griess test ,Internal medicine ,medicine ,Animals ,Secretion ,Molecular Biology ,Incubation ,Cells, Cultured ,Chemokine CCL2 ,Dose-Response Relationship, Drug ,Liver Diseases ,Cell Biology ,General Medicine ,Macrophage Activation ,In vitro ,Rats ,Androstadienes ,NG-Nitroarginine Methyl Ester ,Endocrinology ,chemistry - Abstract
Nitric oxide (NO) and Monocyte Chemoattractant Protein (MCP)-1 co-regulation has been found in endotoxin-activated macrophages. Kupffer cells (KC) are a main source of soluble-mediators production in liver abnormalities. We investigated in vitro similar co-regulation of NO and MCP-1 production in rat activated KC. Isolated rat KC were cultured in the presence of 1 μg/ml LPS and various concentrations of Wortmannin (0–300 nM), L-NAME (0–500 μM) or MCP-1 (0–100 ng/ml). Production of MCP-1 and NO were measured in supernatants, by ELISA and a modification of the Griess reaction, respectively. Growth arrested KC, stimulated with vehicle, produced a basal amount of NO and MCP-1. In the presence of LPS, cultured KC secreted significantly (P < 0.01) increased amounts of MCP-1 and NO. Pre-treatment of KC with various concentrations of L-NAME significantly (P < 0.05) reduced the LPS-induced secretion of NO in a concentration dependent manner, but the MCP-1 production remained unaffected. Pre-treatment with Wortmannin significantly (P < 0.05) inhibited LPS-induced secretion of MCP-1 and NO in a concentration dependent manner. Linear regression analysis revealed a positive correlation between MCP-1 and NO in the LPS (r = 0.59171, P < 0.0001) and Wortmannin (r = 0.9215, P = 0.009) treated groups, but not in the L-NAME (r = −0.08513, P = 0.873). Incubation of KC with various concentrations of MCP-1 did not increase the NO production. These results indicate that KC might be the main source of NO and MCP-1 production in liver disorders, probably through the induction of PI3-kinase(s) and without any co-regulation between these molecules, which might represent two independent immunoregulatory pathways in the role of KC in hepatic disorders.
- Published
- 2008
37. Mannose-binding Lectin MBL2 Gene Polymorphisms and Outcome of Hepatitis C Virus-infected Patients
- Author
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Emmanouil Galanakis, Elias A. Kouroumalis, Christianna Choulaki, Mary Koulentaki, Eirini Koutsounaki, and George N. Goulielmos
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Hepatitis B virus DNA polymerase ,Hepatitis C virus ,Immunology ,chemical and pharmacologic phenomena ,Hepacivirus ,medicine.disease_cause ,Mannose-Binding Lectin ,White People ,Medical microbiology ,Genotype ,medicine ,Humans ,Immunology and Allergy ,Genetic Predisposition to Disease ,Promoter Regions, Genetic ,Aged ,Mannan-binding lectin ,Aged, 80 and over ,Polymorphism, Genetic ,biology ,Lectin ,Exons ,Hepatitis C ,Middle Aged ,Hepatitis B ,bacterial infections and mycoses ,medicine.disease ,Virology ,biology.protein ,Female - Abstract
Mannose-binding lectin (MBL) is involved in host's response to several infections including hepatitis B but little is known about MBL and hepatitis C virus (HCV) infection. The present study attempts to investigate whether MBL2 genotype and serum MBL levels affect the course of HCV infection.We investigated the variant alleles in MBL2 gene promoter and exon-1 regions in 80 Caucasian HCV-infected patients. Mutations in MBL2 were determined by polymerase chain reaction and restriction fragment length polymorphisms analysis. Serum MBL levels were measured by ELISA. Polymorphism homozygosity in exon-1 region was significantly related to lower serum MBL levels (p0.001), to liver inflammation (p = 0.034, OR = 11.7) and, in a lesser degree, to fibrosis. Polymorphisms in promoter sites -221nt and -550nt were not shown to be related with serum MBL levels or progress to liver inflammation and fibrosis. Serum MBL levels were adversely associated with progression to fibrosis (p = 0.037). Response to antiviral treatment was related to hepatitis C virus genotype (p0.001, OR = 10.9), but not to MBL2 genotype or serum MBL levels.These findings suggest that polymorphisms in MBL2 gene exon-1 region are related to low serum MBL levels and progression of HCV infection to liver inflammation and fibrosis.
- Published
- 2008
38. Mechanisms of Action and Resistance of Somatostatin Analogues for the Treatment of Hepatocellular Carcinoma: A Message Not Well Taken
- Author
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George Notas, Elias A. Kouroumalis, Nikolaos Christodoulakis, and Dimitrios Samonakis
- Subjects
endocrine system ,Carcinoma, Hepatocellular ,Physiology ,Octreotide ,Antineoplastic Agents ,Neuroendocrine tumors ,Lanreotide ,Peptides, Cyclic ,chemistry.chemical_compound ,fluids and secretions ,Carcinoma ,medicine ,Humans ,Somatostatin receptor ,business.industry ,Liver Neoplasms ,Gastroenterology ,Cancer ,medicine.disease ,Somatostatin ,chemistry ,Drug Resistance, Neoplasm ,Hepatocellular carcinoma ,Immunology ,Cancer research ,business ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.
- Published
- 2008
39. RT-PCR and immunocytochemistry studies support the presence of somatostatin, cortistatin and somatostatin receptor subtypes in rat Kupffer cells
- Author
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Elias A. Kouroumalis, George Notas, C. Xidakis, E. Renieri, Niki Mastrodimou, George Kolios, and Kyriaki Thermos
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Time Factors ,Kupffer Cells ,Physiology ,Blotting, Western ,Clinical Biochemistry ,Biology ,Biochemistry ,Cortistatin (neuropeptide) ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Endocrinology ,Internal medicine ,Somatostatin receptor 3 ,medicine ,Animals ,Somatostatin receptor 2 ,Somatostatin receptor 1 ,RNA, Messenger ,Receptors, Somatostatin ,Cells, Cultured ,Delta cell ,Reverse Transcriptase Polymerase Chain Reaction ,Somatostatin receptor ,Neuropeptides ,Kupffer cell ,Immunohistochemistry ,Molecular biology ,Rats ,Somatostatin ,medicine.anatomical_structure ,hormones, hormone substitutes, and hormone antagonists - Abstract
The present study investigated the presence of somatostatin receptor subtypes (ssts) and the endogenous peptides somatostatin and cortistatin in rat Kupffer cells, since modulation of these cells by somatostatin may be important for the beneficial effect of somatostatin analogues in a selected group of hepatocellular carcinoma patients. Kupffer cells were isolated from rat liver in agreement with national and EU guidelines. RT-PCR was employed to assess the expression of somatostatin, cortistatin and ssts in Kupffer cells. Western blot analysis and immunocytochemistry were employed to assess the expression and the localization of the receptors, respectively. Quiescent Kupffer cells were found to express sst(1-4) mRNA, while immunocytochemical studies supported the presence of only the sst(3) and sst(4) receptors, which were found to be internalized. However, sst1 and sst(2A) receptors were detected by western blotting. RT-PCR and RIA measurements support the presence of both somatostatin and cortistatin. Stimulation of the cells with LPS activated the expression of the sst(2), sst(3) and sst(4) receptors. The present data provide evidence to support the presence of ssts and the endogenous neuropeptides somatostatin and CST in rat Kupffer cells. Both peptides may act in an autocrine manner to regulate sst receptor distribution. Studies are in progress in order to further characterize the role of ssts in Kupffer cells and in hepatic therapeutics.
- Published
- 2007
40. The effect of infliximab on circulating levels of leptin, adiponectin and resistin in patients with inflammatory bowel disease
- Author
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Konstantinos Karmiris, C. Xidakis, Elias A. Kouroumalis, Ioannis E. Koutroubakis, and Maria Polychronaki
- Subjects
Adult ,Leptin ,Male ,medicine.medical_specialty ,Peptide Hormones ,Adipokine ,Inflammatory bowel disease ,Body Mass Index ,Gastrointestinal Agents ,Internal medicine ,medicine ,Humans ,Resistin ,Prospective Studies ,Crohn's disease ,Hepatology ,Adiponectin ,Tumor Necrosis Factor-alpha ,business.industry ,Gastroenterology ,Antibodies, Monoclonal ,Middle Aged ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,Infliximab ,digestive system diseases ,C-Reactive Protein ,Endocrinology ,Immunology ,Female ,business ,Biomarkers ,medicine.drug - Abstract
Tumour necrosis factor alpha is a critical mediator of inflammation-related altered metabolism in inflammatory bowel disease (IBD), possibly through its interaction with adipokines, which play an important role in IBD. Infliximab is a well established antitumour necrosis factor alpha treatment in IBD.We studied serum levels of leptin, adiponectin and resistin in 20 IBD patients before and after infliximab treatment using commercially available enzyme-linked immunosorbent assays. The results were correlated with alterations of disease activity, BMI and C-reactive protein.Infliximab induced clinical response or remission in 18 out of 20 treated IBD patients. Mean serum-leptin levels were 4.6+/-0.5 and 5.1+/-0.5 ng/ml (P=0.41), mean serum-adiponectin levels were 10513.9+/-1216.9 and 9653.5+/-1031.5 ng/ml (P=0.36) and mean serum-resistin levels were 26.3+/-4.1 and 13.9+/-1.4 ng/ml (P=0.004), before and after infliximab treatment, respectively. No significant correlation between the changes of BMI, C-reactive protein or the clinical indices of activity and alterations of the examined adipokines was found.Serum levels of leptin and adiponectin had no significant alterations, whereas serum-resistin levels are significantly decreased after infliximab therapy in IBD patients, suggesting a possible proinflammatory status for resistin in IBD and a role as a marker of successful therapy.
- Published
- 2007
41. Ileal Malignant Melanoma Causing Intussusception: Report of a Case
- Author
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Maria Tzardi, Elias A. Kouroumalis, Maria Roussomoustakaki, John Romanos, John Grammatikakis, Konstantinos Karmiris, Manolis Papadakis, and Maria Polychronaki
- Subjects
Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Ileum ,Lesion ,Fatal Outcome ,Intussusception (medical disorder) ,Laparotomy ,Humans ,Medicine ,Melanoma ,Aged ,Gastrointestinal tract ,Brain Neoplasms ,business.industry ,General Medicine ,Anus ,medicine.disease ,Small intestine ,Ileal Neoplasms ,medicine.anatomical_structure ,Female ,Surgery ,medicine.symptom ,business ,Intussusception ,Brain metastasis - Abstract
Cutaneous malignant melanoma (MM) often metastasizes to the gastrointestinal (GI) tract; however, primary MM of the small intestine is a controversial diagnosis. We report the case of a 76-year-old woman found to have a primary MM in the ileum. After clinical evaluation, the radiological workup, which included magnetic resonance enteroclysis (MRE), revealed a large polypoid intraluminal tumor. She underwent laparotomy and the lesion was excised. Histological examination of the resected specimen revealed morphological and immunohistochemical characteristics of MM and a detailed postoperative examination failed to identify a primary lesion on the skin, anus, oculus, or any other site. The patient died of brain metastasis 6 months after surgery. According to our review of the literature, this is the first case of primary MM of the small intestine diagnosed with the help of MRE.
- Published
- 2007
42. Geoepidemiology of hepatocellular carcinoma in the island of Crete, Greece. A possible role of pesticides
- Author
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Spyridon A. Karageorgos, Dimitrios Samonakis, Emmanuel Digenakis, Dimitra Sifaki-Pistolla, Elias A. Kouroumalis, Mairi Koulentaki, and Soultana Stratakou
- Subjects
Adult ,Male ,Carcinoma, Hepatocellular ,Time Factors ,Hepatitis C virus ,Population ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine ,Prevalence ,Humans ,Pesticides ,education ,Aged ,Retrospective Studies ,Hepatitis B virus ,Aged, 80 and over ,education.field_of_study ,Hepatology ,Greece ,Liver Neoplasms ,Hepatitis C ,Environmental exposure ,Environmental Exposure ,Hepatitis B ,Place of birth ,Middle Aged ,medicine.disease ,Virology ,Health Surveys ,digestive system diseases ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Female ,Demography - Abstract
Background & Aims Geoepidemiological data of hepatocellular carcinoma (HCC) are lacking. Crete has a genetically homogeneous population and is suitable for studies to identify a possible contribution of environmental factors in HCC. Methods Databases for HCC (316 cases), hepatitis B virus (HBV) (633) and hepatitis C virus (HCV) (392), constructed over the past 20 years in our Unit, were used. Data included place of birth and place of residence for the last 15 years. Hellenic Statistical Authority provided population statistics from 1980 to 2014. Time-spatial methods were applied in Gis-ArcMap 10 software. Spatial autocorrelation tests (Moran's index) detected differences between the spatial distribution to place of residence. Spatial density maps were created. Kriging Interpolation was applied, to produce prediction maps of HCC. Results Hepatitis C virus appears in areas of high prevalence while HBV is uniformly distributed. HCC is more prevalent in Eastern Crete. A spatial autocorrelation between HCC and either HCV (Moran's I = 0.88, P < 0.001) or HBV (I = 0.84, P < 0.02) was found as expected. However, there is a discrepancy in the South East of Crete, where a higher prevalence of HCC than expected was observed. This is an area where extensive use of pesticides in large green houses is practiced. Conclusions Hepatocellular carcinoma is associated with the dispersion of HCV and HBVs. In an area with widespread use of pesticides, a higher than expected spatial distribution of HCC was detected.
- Published
- 2015
43. Resveratrol exerts its antiproliferative effect on HepG2 hepatocellular carcinoma cells, by inducing cell cycle arrest, and NOS activation
- Author
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Elias Castanas, Marilena Kampa, Joseph Vercauteren, Artemissia-Phoebe Nifli, George Notas, and Elias A. Kouroumalis
- Subjects
G2 Phase ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Time Factors ,Cell cycle checkpoint ,Transcription, Genetic ,medicine.medical_treatment ,Biophysics ,Apoptosis ,Biology ,Resveratrol ,Nitric Oxide ,Biochemistry ,chemistry.chemical_compound ,Internal medicine ,Stilbenes ,Tumor Cells, Cultured ,medicine ,Humans ,Molecular Biology ,Cell Proliferation ,chemistry.chemical_classification ,Reactive oxygen species ,Cell growth ,Growth factor ,Cell Cycle ,Liver Neoplasms ,G1 Phase ,Hormone receptor binding ,Cell cycle ,Antineoplastic Agents, Phytogenic ,Endocrinology ,chemistry ,Cancer research ,Nitric Oxide Synthase ,Reactive Oxygen Species - Abstract
The stilbene resveratrol exerts antiproliferative and proapoptotic actions on a number of different cancer cell lines, through diverse mechanisms, including antioxidant effects, enzyme, growth factor and hormone receptor binding, and nucleic acid direct or indirect interactions. Although resveratrol accumulates in the liver, its effect on hepatocellular carcinoma has not been extensively studied. We have used the human hepatocyte-derived cancer cell line HepG2 to address the possible action of resveratrol on cell growth and to examine some possible mechanisms of action. Our results indicate that the stilbene inhibits potently cell proliferation, reduces the production of reactive oxygen species and induces apoptosis, through cell cycle arrest in G1 and G2/M phases. Furthermore it modulates the NO/NOS system, by increasing iNOS and eNOS expression, NOS activity and NO production. Inhibition of NOS enzymes attenuates its antiproliferative effect. These data could be of value in possible prevention or adjuvant treatment of hepatocellular carcinoma, through an increased consumption of resveratrol-rich foods and beverages.
- Published
- 2006
44. Pancreatic Autoantibodies in Greek Patients with Inflammatory Bowel Disease
- Author
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Elias A. Kouroumalis, Ioannis E. Koutroubakis, Dimitrios Drygiannakis, Konstantinos Karmiris, Ioannis Drygiannakis, and Sokratis Makreas
- Subjects
Adult ,Male ,medicine.medical_specialty ,Physiology ,medicine.disease_cause ,Sensitivity and Specificity ,Severity of Illness Index ,Inflammatory bowel disease ,Autoimmunity ,Cohort Studies ,Age Distribution ,Crohn Disease ,Reference Values ,Internal medicine ,Prevalence ,medicine ,Humans ,Sex Distribution ,Colitis ,Fluorescent Antibody Technique, Indirect ,Pancreas ,Aged ,Autoantibodies ,Probability ,Crohn's disease ,Greece ,business.industry ,Gastroenterology ,Case-control study ,Autoantibody ,Middle Aged ,Hepatology ,Inflammatory Bowel Diseases ,Prognosis ,medicine.disease ,Ulcerative colitis ,Case-Control Studies ,Immunology ,Colitis, Ulcerative ,Female ,business ,Biomarkers - Abstract
Pancreatic autoantibodies (PAbs) have been suggested as a specific but not sensitive marker for Crohn's disease (CD). The aim of this study was to assess the value of detecting PAbs in Greek patients with ulcerative colitis (UC) and CD. Sera were collected from 150 patients with IBD (73 with UC and 77 with CD), 31 cases with non-IBD intestinal inflammation, 16 cases with other autoimmune diseases, and 104 healthy controls. Determination of PAbs was performed by a standard indirect immunofluorescence technique. PAbs were detected in 18 of 73 (24.7%) samples from UC patients and in 32 of 77 (41.6%) samples from CD patients. The prevalence of positive PAbs was significantly higher in CD than in UC (P = 0.04). None of the 104 samples from healthy controls and the 31 cases with non-IBD intestinal inflammation had detectable PAbs. One patient with Sjogren's syndrome was PAbs positive. No association of PAbs with IBD activity, IBD localization, or medical treatment was found. Patients with stenotic CD had a significantly higher prevalence of PAbs positivity (60%) compared with patients with inflammatory (28.6%) and fistulizing (41.2%) disease (P = 0.02). The prevalence of PAbs in Greek CD patients was found to be similar to that in previous reports. In contrast to these studies we found also increased prevalence of PAbs in UC patients. These findings suggest that PAbs should be considered as a specific marker for IBD rather than for CD.
- Published
- 2005
45. The Emerging Role of Adipocytokines as Inflammatory Mediators in Inflammatory Bowel Disease
- Author
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Ioannis E. Koutroubakis, Konstantinos Karmiris, and Elias A. Kouroumalis
- Subjects
Leptin ,medicine.medical_specialty ,Peptide Hormones ,Adipose tissue ,Adipokine ,White adipose tissue ,Inflammatory bowel disease ,Internal medicine ,Adipocytes ,medicine ,Humans ,Immunology and Allergy ,Mesentery ,Resistin ,Crohn's disease ,Adiponectin ,business.industry ,Gastroenterology ,Inflammatory Bowel Diseases ,medicine.disease ,Ghrelin ,digestive system diseases ,Endocrinology ,Immunology ,business - Abstract
Anorexia, malnutrition, altered body composition and development of mesenteric obesity are well known features of inflammatory bowel disease (IBD). Recent data suggest that dysregulation of protein secretion by white adipose tissue is involved in these manifestations of patients with IBD. Adipocytes are recently recognized as endocrine cells that secrete a variety of bioactive substances known as adipocytokines. There is evidence that adipocytokines are involved in inflammatory and metabolic pathways in human beings. Overexpression of adipocytokines such as leptin, adiponectin and resistin in mesenteric adipose tissue of operated patients with Crohn's disease has recently been reported, suggesting that mesenteric adipocytes in IBD may act as immunoregulating cells. Therefore, it could be suggested that adipocytokines play an important role in the disease pathogenesis. Moreover, modulators of mesenteric adipose function have been suggested as potential therapeutic drugs in IBD. In this review, the importance of white adipose tissue function and adipocytokines, is discussed with respect to IBD.
- Published
- 2005
46. Production of Pro- and Anti-fibrotic Agents by Rat Kupffer Cells; The Effect of Octreotide
- Author
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Elias A. Kouroumalis, Dushanka Ljumovic, C. Xidakis, Pinelopi Manousou, Vassilis Valatas, George Notas, and George Kolios
- Subjects
Leptin ,Lipopolysaccharides ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Kupffer Cells ,Physiology ,medicine.medical_treatment ,Cell Culture Techniques ,Octreotide ,Biology ,Rats, Sprague-Dawley ,Transforming Growth Factor beta1 ,chemistry.chemical_compound ,Gastrointestinal Agents ,Transforming Growth Factor beta ,Fibrosis ,Internal medicine ,medicine ,Animals ,Kupffer cell ,Gastroenterology ,medicine.disease ,Urokinase-Type Plasminogen Activator ,Matrix Metalloproteinases ,Rats ,Endocrinology ,Cytokine ,medicine.anatomical_structure ,Somatostatin ,chemistry ,Cell culture ,Plasminogen activator ,medicine.drug - Abstract
Kupffer cells may be involved in liver fibrogenesis through production of TGF-beta1. Their role in fibrinolysis is less clear. Octreotide, a synthetic analogue of somatostatin, is often used in cirrhotic patients. Its effect on Kupffer cells was studied. Isolated rat Kupffer cells were cultured in the presence of lipopolysaccharide and/or octreotide. TGF-beta1, leptin, collagenase (MMP-1), and urokinase-type plasminogen activator (uPA) were assessed in supernatants by ELISA, and MMP-2 and MMP-9 by zymography. Kupffer cells produced large amounts of MMP-1 and lipopolysaccharide induced a significant (P < 0.02) early increase. Octreotide and lipopolysaccharide caused a synergistic effect on MMP-1 secretion. By contrast, MMP-9 production stimulated by lipopolysaccharide was suppressed by octreotide. Kupffer cells produced a basal amount of uPA, significantly increased after lipopolysaccharide or octreotide incubation (P < 0.001). Large amounts of TGF-beta1 were produced in a time-dependent manner by unstimulated Kupffer cells. Lipopolysaccharide and octreotide, alone or in combination, induced a significant inhibition of this production (P < 0.01). Kupffer cells did not produce leptin, a recently identified mediator of liver fibrosis, or MMP-2. Kupffer cells may play a significant role in liver fibrinolysis. Octreotide, acting on TGF-beta1, uPA, and MMP-1 production, may be a useful agent for fibrosis resolution.
- Published
- 2005
47. Differential expression of matrix metalloproteinases in viral and non-viral chronic liver diseases
- Author
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Athanasios Alegakis, Elias A. Kouroumalis, Dusanka Ljumovic, and Ioannis Diamantis
- Subjects
Pathology ,medicine.medical_specialty ,DNA, Complementary ,Hepatitis, Viral, Human ,Biopsy ,Clinical Biochemistry ,Matrix metalloproteinase ,Biochemistry ,Hepatitis ,Liver disease ,Hepatitis B, Chronic ,Matrix Metalloproteinase 10 ,Matrix Metalloproteinase 11 ,Fibrosis ,medicine ,Humans ,medicine.diagnostic_test ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Liver Diseases ,Biochemistry (medical) ,Metalloendopeptidases ,General Medicine ,Hepatitis C ,Hepatitis C, Chronic ,Hepatitis B ,medicine.disease ,Matrix Metalloproteinases ,Matrix Metalloproteinase 9 ,Chronic Disease ,Immunology ,Matrix Metalloproteinase 2 ,RNA ,Steatohepatitis ,business - Abstract
Background Fibrosis is a common consequence of chronic liver diseases irrespective of aetiology. Metalloproteinases play an important role in the fibrotic process participating in the balance between collagen synthesis and degradation. We examined whether matrix gelatinases and stromelysins are similarly involved in the development of viral (HCV, HBV) and non-viral (NASH) liver diseases. Methods Hepatic mRNA levels of matrix metalloproteinase MMP-2, MMP-9, MMP-10 and MMP-11 isolated from liver biopsies were measured by semi-quantitative RT-PCR. Seventy-three patients were examined in this study: non-diseased controls (10), patients with chronic hepatitis B (14), chronic hepatitis C (33) and non-alcoholic steatohepatitis (16). Results A significant increase of MMP-9 and MMP-10 expression was found in patients with non-viral (non-alcoholic steatohepatitis) liver disease. Patients with chronic hepatitis B and hepatitis C showed an increase in MMP-2 mRNA expression compared to controls. Moreover, chronic hepatitis B and hepatitis C patients had significantly different mRNA expression patterns. Conclusions These findings indicate that matrix metalloproteinases are differentially involved in the fibrotic process of viral and non-viral chronic liver diseases. Differences exist between HBV and HCV chronic hepatitis. Differences between early and late fibrosis indicate that in future studies, careful staging of patients is mandatory for interpretation of results.
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- 2004
48. Decreased Total and Corrected Antioxidant Capacity in Patients with Inflammatory Bowel Disease
- Author
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Elias Castanas, Ioannis E. Koutroubakis, Niki Malliaraki, Philippos Dimoulios, Elias A. Kouroumalis, and Konstantinos Karmiris
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Adult ,Male ,medicine.medical_specialty ,Physiology ,Bilirubin ,medicine.disease_cause ,Risk Assessment ,Sensitivity and Specificity ,Severity of Illness Index ,Gastroenterology ,Inflammatory bowel disease ,Antioxidants ,Cohort Studies ,chemistry.chemical_compound ,Crohn Disease ,Reference Values ,Internal medicine ,Humans ,Medicine ,Colitis ,Aged ,Probability ,Analysis of Variance ,Crohn's disease ,business.industry ,Albumin ,Middle Aged ,Inflammatory Bowel Diseases ,Prognosis ,medicine.disease ,Ulcerative colitis ,Oxidative Stress ,stomatognathic diseases ,chemistry ,Immunology ,Disease Progression ,Uric acid ,Colitis, Ulcerative ,Female ,business ,Biomarkers ,Oxidative stress - Abstract
Oxidative stress and depletion of antioxidants may play a key role in the pathogenesis of inflammatory bowel disease (IBD)-related intestinal damage. A new automated assay for the determination of blood total antioxidant capacity (TAC), based on the crocin bleaching method, has been used for the measurement of TAC and corrected TAC (cTAC) in patients with ulcerative colitis (UC) and Crohn's disease (CD) in comparison to healthy controls (HC). Ninety-four patients with UC, 97 patients with CD, and 72 HC were included in this study. Serum TAC was measured in all patients and controls on an Olympus AU-600 chemistry analyzer using a TAC kit. cTAC was calculated from TAC after subtraction of the interactions due to endogenous uric acid, bilirubin and albumin. Mean serum TAC as well as cTAC levels were significantly lower in both UC and CD patients compared with HC (P
- Published
- 2004
49. Survival of Anti-Mitochondrial Antibody-Positive and -Negative Primary Biliary Cirrhosis Patients on Ursodeoxycholic Acid Treatment
- Author
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Joanna Moscandrea, M Koulentaki, Costas Chatzicostas, Philipos Dimoulios, and Elias A. Kouroumalis
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Male ,Cholagogues and Choleretics ,medicine.medical_specialty ,Physiology ,medicine.drug_class ,medicine.medical_treatment ,Population ,Liver transplantation ,Risk Assessment ,Gastroenterology ,Antibodies ,Primary biliary cirrhosis ,Internal medicine ,medicine ,Humans ,education ,Survival analysis ,education.field_of_study ,Bile acid ,Liver Cirrhosis, Biliary ,business.industry ,Ursodeoxycholic Acid ,Middle Aged ,Hepatology ,medicine.disease ,Survival Analysis ,Ursodeoxycholic acid ,Mitochondria ,Antibodies, Antinuclear ,Female ,business ,medicine.drug ,Anti-mitochondrial antibody - Abstract
The survival of 85 anti-mitochondrial antibody (AMA)-positive (mean Mayo risk score, 5.11) and 19 AMA-negative (mean Mayo risk score, 4.77) primary biliary cirrhosis patients, under ursodeoxycholic acid not subjected to liver transplantation, was compared with the estimated survival of a simulated control group of untreated patients created with the updated Mayo model and a control group from the general population. In the first 7 years 3 AMA-negative patients died, versus 12 under the Mayo model (P = 0.01), and 10 AMA-positive patients, versus 26 under the Mayo model (P < 0.005), with 7 expected deaths from the general population (P < 0.0001). At 10 years the cumulative survival differed in the treated patients overall (P < 0.0001) but not in the early primary biliary cirrhosis (stages I-II) patients compared to the general population. Therefore the survival of our patients treated with ursodeoxycholic acid is higher than that predicted from the Mayo model. Early treatment may prolong survival.
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- 2004
50. Secretion of inflammatory mediators by isolated rat Kupffer cells: the effect of octreotide
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George Kolios, C. Xidakis, Pinelopi Manousou, Elias A. Kouroumalis, George Notas, Vassilis Valatas, and Dusanka Ljumovic
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medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Kupffer Cells ,Physiology ,Clinical Biochemistry ,Octreotide ,Enzyme-Linked Immunosorbent Assay ,Inflammation ,Biology ,Peptide hormone ,Nitric Oxide ,Biochemistry ,Nitric oxide ,Wortmannin ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,medicine ,Animals ,Interleukin-13 ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Kupffer cell ,Interleukin-12 ,Interleukin-10 ,Rats ,Somatostatin ,medicine.anatomical_structure ,chemistry ,Tumor necrosis factor alpha ,medicine.symptom ,medicine.drug - Abstract
Aims: We studied the production of inflammatory mediators by rat KC and the possible in vitro effect of the somatostatin analogue octreotide. Methods: Primary KC cultures were incubated with LPS added alone or with different concentrations of octreotide. The production of TNFα, IL-6, IL-10, IL-12 and IL-13 was assessed in culture supernatants by ELISA and that of nitric oxide (NO) by a modification of the Griess reaction. Results: Isolated KC produced a basal amount of TNFα, IL-6, IL-12, IL-13, and NO but not IL-10. LPS-stimulated KC secreted significantly increased amounts of TNFα (P
- Published
- 2004
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