Papers by Ilias Kouroumalis
European Journal of Gastroenterology & Hepatology, Apr 1, 2006
The combination of intravenous iron and recombinant human erythropoietin has been proved to be ef... more The combination of intravenous iron and recombinant human erythropoietin has been proved to be effective in the treatment of refractory anaemia in patients with inflammatory bowel disease (IBD). Darbepoetin-alpha (DPO) has a three-fold longer terminal half-life than erythropoietin. The purpose of this pilot study was to determine whether darbepoetin-alpha is also effective for the treatment of refractory anaemia in IBD. Twenty IBD patients (nine ulcerative colitis and 11 Crohn's disease) and refractory anaemia received intravenous iron sucrose (total iron dose 1.3+/-0.5 g, range 0.7-1.9) and darbepoetin-alfa at the single, weekly dose of 0.9 microg/kg subcutaneously for 4 weeks. Serum erythropoietin, ferritin, transferrin, soluble transferrin receptor, C-reactive protein and interleukin-6 were measured at baseline and after treatment. Haematopoietic response (increase of haemoglobin > or = 2.0 g/dl) was observed in 15 out of the 20 patients (75%). The mean haemoglobin concentrations increased from 9.48+/-0.82 g/dl at baseline to 12.71+/-1.12 g/dl after treatment (P<0.0001). Mean corpuscular volume and serum ferritin levels were also significantly increased whereas mean C-reactive protein levels and endogenous erythropoietin levels significantly decreased after treatment. In IBD patients with refractory anaemia the administration of darbepoetin in combination with intravenous iron sucrose can raise haemoglobin levels.
European Journal of Clinical Investigation, Feb 1, 2006
Background Angiogenesis has been suggested to play an important role in inflammatory bowel diseas... more Background Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD). Materials and methods Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease. Results Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0•05 and P < 0•001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0•04) median serum Ang-2 levels but significantly lower (P = 0•02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0•02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin. Conclusions Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD.
Journal of Crohn's and Colitis Supplements, Mar 1, 2007
British Journal of Pharmacology, Feb 1, 2004
Kupffer cells (KC) and lipopolysaccharide (LPS) interaction is the initial event leading to hepat... more Kupffer cells (KC) and lipopolysaccharide (LPS) interaction is the initial event leading to hepatic inflammation and fibrosis in many types of liver injury. We studied chemokine secretion by KC activated with LPS and the possible effect of the somatostatin analogue octreotide, in the regulation of this process. 2 KC isolated from Sprague-Dawley rats were cultured in the presence of LPS added alone or with different concentrations of octreotide for 24 and 48 h, and chemokine production was assessed in culture supernatants by ELISA. CC chemokine mRNA expression was assessed by semiquantitative RT-PCR. 3 Vehicle-stimulated KC produced a basal amount of CC and CXC chemokines. LPS-stimulated KC secreted significantly increased amounts of IL-8 (GRO/CINC-1) (Po0.001), MIP-2 (Po0.001), MCP-1 (Po0.001), and RANTES (Po0.01). 4 Octreotide inhibited LPS-induced secretion of the CC chemokines MCP-1 (Po0.05) and RANTES (Po0.05), but not the CXC chemokines IL-8 (GRO/CINC-1) and MIP-2, in a concentration-dependent manner. Downregulation of basal and LPS-induced mRNA expression of the CC chemokines was also observed in the presence of octreotide. 5 Pretreatment with phosphatidylinositol 3 (PI3)-kinase inhibitors reduced chemokine production by LPS-treated KC in both the mRNA and protein level. Furthermore, it prevented the octreotide inhibitory effect on LPS-induced chemokine secretion, indicating a possible involvement of the PI3kinase pathway. 6 In conclusion, these data demonstrate that chemokine secretion by KC can be differentially regulated by octreotide, and suggest that this somatostatin analogue may have immunoregulatory effects on resident liver macrophages.
Biomedicines, Dec 8, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Healthcare
Malnutrition is highly prevalent in liver cirrhosis (LC). It increases as the severity of the dis... more Malnutrition is highly prevalent in liver cirrhosis (LC). It increases as the severity of the disease progresses and it is related to poor survival. The objectives of the study were the nutritional assessment of Greek LC patients, using various nutritional assessment and screening tools, and the comparison of their predictive value for mortality. In total, 137 (77 male) consecutive LC patients (median age: 67 years) were assessed with subjective global assessment (SGA) and mini nutritional assessment (MNA) questionnaires, anthropometrics, handgrip strength (HGS) tests, and bioelectric impedance analysis (BIA), in comparison to a control group of 148 healthy people. Disease severity was assessed using the model for end-stage liver disease (MELD) scores. Patients were followed up for a median of 19 months. Survival curves were calculated using the Kaplan–Meier method. In total, 60% and 43% of patients were of adequate nutritional status by SGA and MNA, respectively, which was confirme...
Journal of Cell Science, 1999
Using autoimmune antibodies from a patient with primary biliary cirrhosis we have identified a 68... more Using autoimmune antibodies from a patient with primary biliary cirrhosis we have identified a 68 kDa nuclear envelope protein, termed PBC68. This protein is co-precipitated with a 98 kDa and a 250 kDa polypeptide and is distinct from the nuclear lamins. Immunostaining of digitonin-permeabilized cells indicates that PBC68 is restricted to the inner (nucleoplasmic) face of the nuclear envelope, while indirect immunofluorescence and immunoelectron microscopy show that PBC68 is located on fibrillar structures emanating from the nuclear pore complex. The autoantigen is modified at early prophase and disassembles at prometaphase concurrently with the breakdown of the nuclear envelope. The disassembled material, instead of diffusing throughout the cytoplasm as other nucleoporins, is targeted to the mitotic spindle and remains stably bound to it until anaphase. At telophase PBC68 is released from the mitotic apparatus and reassembles late, after incorporation of LAP2B and B-type lamins, on...
Gut, 2014
Conclusion Our novel multi-parameter analyses of live cells prepared from fresh colonic and ileal... more Conclusion Our novel multi-parameter analyses of live cells prepared from fresh colonic and ileal biopsies enable precise examination of the disease-inducing and effector populations that drive UC and CD. We are using the methods described here to dissect the immunological mechanisms driving inflammation in patients with IBD. We anticipate that our ongoing comparisons of each of these immune cell populations in blood and intestinal biopsies from unaffected individuals, CD, and UC patients will reveal important details about pathogenic mechanisms controlling intestinal inflammation. Disclosure of Interest None Declared.
Journal of Crohn's and Colitis Supplements, 2008
Conclusion: This study reinforced the increased risk associated with smoking history and appendec... more Conclusion: This study reinforced the increased risk associated with smoking history and appendectomy in UC. However, a number of significant associations with CD and UC on univariate and multivariate analysis may support the "hygiene hypothesis" and may provide new etiological clues.
Journal of Crohn's and Colitis, 2014
Clinical: Diagnosis & outcome S175 >40 (18% vs 5%) and more common among CH (21% vs 7% MAL, 0% IN... more Clinical: Diagnosis & outcome S175 >40 (18% vs 5%) and more common among CH (21% vs 7% MAL, 0% IND, p = 0.02). Among Anti-HBc-ve patients, only 43 (39%) were anti-HBs+ (vaccinated). A significantly greater proportion of female patients (73% vs 53%, p = 0.03) and a trend for those age >40 (67% vs 51%, p = 0.1) were not vaccinated. Conclusions: The prevalence of HBV/HCV infection among Asian IBD patients in Singapore is similar to the general population. Physicians should be reminded regarding HBV screening (16% not screened) and vaccination (61% not vaccinated), especially among Chinese/age >40 (HBV infection) and women/age >40 (vaccination).
Journal of Crohn's and Colitis, 2009
Clinical and Experimental Immunology, 2010
SummaryHuman colonic epithelial cells express T helper type 1 (Th1)-associated chemoattractants, ... more SummaryHuman colonic epithelial cells express T helper type 1 (Th1)-associated chemoattractants, yet little is known about the production of Th2-associated chemoattractants. CCL11/eotaxin-1, CCL24/eotaxin-2 and CCL26/eotaxin-3 are known to attract CCR3-expressing, Th2-polarized lymphocytes. We studied constitutive and inflammation-induced expression and production of CCR3 together with its ligands in the colon and peripheral blood of patients with inflammatory bowel disease (IBD) by flow cytometry, reverse transcription–polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA). We further defined the regulated expression of these chemokines by RT–PCR and ELISA using cultured human epithelial cell lines. A higher fraction of peripheral T lymphocytes were found to be positive for CCR3 in patients with ulcerative colitis (UC) compared to Crohn's disease (CD), while almost no CCR3+ T cells were found in normal controls (NC). Similarly, higher and more frequent...
Alcohol and Alcoholism, 2004
BACKGROUND Binge alcohol consumption has been arbitrarily defined as five drinks in a row for men... more BACKGROUND Binge alcohol consumption has been arbitrarily defined as five drinks in a row for men and four drinks in a row for women, consumed over a short period of time. It seems that this type of alcohol consumption is not uncommon, at least in the western world. In 1993, 39% of college students binged at least three times every month, while in 1995 an increase to 52% of students was noted (Wechsler et al., 1998). Binge drinking has been experimentally shown to exacerbate acetaminophen induced centrilobular injury (De Leve et al., 1997). Moreover, in rats alcohol binging caused activation of Kupffer cells with resultant increase of phagocytic activity, prolonged release of TNFα and persisting superoxides for 24 h, although blood alcohol levels had returned to normal 12 h after the last dose of alcohol (Abril et al., 1999). Nitric oxide (NO) plays an important role in the regulation of portal vein pressure and influences splachnic vasodilatation in cirrhotic patients (Vallance et al., 1991). Moreover, NO overproduction precedes hyperdynamic splachnic circulation in rats with experimental portal hypertension (Wiest et al., 1999). It is known that in rats' Kupffer cells excessive production of NO is diminished by chronic alcohol administration (Kimura et al., 1996). The effect of binge drinking on the production of NO metabolites in patients with chronic liver disease has not been studied before. We therefore studied the effect of acute alcohol administration on NOx serum levels in patients with viral and alcoholic cirrhosis and compared them with healthy controls and patients with chronic viral hepatitis.
Hepatoma Research
Soon after introducing direct-acting antiviral agents (DAAs) for chronic hepatitis C treatment, t... more Soon after introducing direct-acting antiviral agents (DAAs) for chronic hepatitis C treatment, there began a debate over the possibility of hepatocellular carcinoma (HCC) after viral clearance. Although several reports suggested that the question has been answered negatively, other reports suggested the opposite. The present review presents data in favor and against the null hypothesis and analyzes the scientific background of the possible participation of DAAs in HCC development. The reasons for the discrepancy among studies are presented. These include heterogeneity of patient selection, the nature of the studies, and the tumors themselves are responsible for varying results. Exogenous factors like alcohol consumption or metabolic syndrome confound these findings and suggest the need for statistical adjustments. The need for careful attention to the statistical details is exemplified, and the significant points of almost universal agreements are identified. The conclusion is that...
Cancers
The HCC constitutes one of the most frequent cancers, with a non-decreasing trend in disease mort... more The HCC constitutes one of the most frequent cancers, with a non-decreasing trend in disease mortality despite advances in systemic therapy and surgery. This trend is fueled by the rise of an obesity wave which is prominent the Western populations and has reshaped the etiologic landscape of HCC. Interest in the nucleotide-binding domain leucine-rich repeat containing (NLR) family member NLRP3 has recently been revived since it would appear that, by generating inflammasomes, it participates in several physiologic processes and its dysfunction leads to disease. The NLRP3 inflammasome has been studied in depth, and its influence in HCC pathogenesis has been extensively documented during the past quinquennial. Since inflammation comprises a major regulator of carcinogenesis, it is of paramount importance an attempt to evaluate the contribution of the NLRP3 inflammasome to the generation and management of HCC. The aim of this review was to examine the literature in order to determine the...
Optimized detection of circulating anti-nuclear envelope autoantibodies by immunofluorescence
Title: Primary Biliary Cirrhosis in a genetically homogeneous population: Disease associations an... more Title: Primary Biliary Cirrhosis in a genetically homogeneous population: Disease associations and familial occurence rates.
Cancers, 2019
Background: Cyclooxygenase 2 (COX-2) is involved in the initial steps of colorectal cancer (CRC) ... more 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...
The International Journal of Biological Markers, 2001
Twenty-two different protein measurements were taken in the serum and ascitic fluid of fifty cons... more Twenty-two different protein measurements were taken in the serum and ascitic fluid of fifty consecutive patients in an attempt to investigate which tests are the most reliable for the differential diagnosis of ascites. Serum and ascitic fluid total proteins (TPR), albumin (ALB), lactate (LAC), ferritin (FER), C3 and C4 complement factors, C-reactive protein (CRP), ceruloplasmin (CER), α2-macroglobulin (α2MG), haptoglobin (HAP), α1-antitrypsin (α1AT), α1-acid glycoprotein (α1AG), transferrin (TRF), immunoglobulins IgG, IgA, IgM and cytokines such as interleukin-1α (IL-1α), interleukin-1α (IL-1α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) were measured to distinguish between malignant and cirrhotic ascites. Correlations and non-parametric Mann-Whitney tests were used for ascitic fluid:serum ratio comparisons between the two groups. Multivariate analyses were used to determine the most significant biochemical ratio predict...
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Papers by Ilias Kouroumalis