M. Zotti

Mucosal assessment of tumor necrosis factor alpha levels on paraffined samples: a comparison between immunohistochemistry and real time polymerase chain reaction

Author(s) : Enzo IerardiArticle title : Mucosal assessment of tumor necrosis factor alpha levels on paraffined samples:a comparison between immunohistochemistry and real time polymerase chainreactionArticle no : 483739Dear Author,Please check these proofs carefully. It is the responsibility of the corresponding author to checkagainst the original manuscript and approve or amend these proofs. A second proof is notnormally provided. Informa Healthcare cannot be held responsible for uncorrected errors, even ifintroduced during the composition process. The journal reserves the right to charge for excessiveauthor alterations, or for changes requested after the proofing stage has concluded.The following queries have arisen during the editing of your manuscript and are marked in themargins of the proofs. Unless advised otherwise, submit all corrections using the CATS onlinecorrection form. Once you have added all your corrections, please ensure you press the “SubmitAll Corrections” button.

Metabolic syndrome and gastro-esophageal reflux: A link towards a growing interest in developed countries

The aim of this Editorial is to describe the growing possibility of a link between gastro-esophageal reflux disease (GERD) and metabolic syndrome on the light of recent epidemiological and pathophysiological evidence. The state of the art of GERD is described, based on recent definitions, pathophysiological evidence, epidemiology in developed countries, clinical subtypes together with a diagnostic approach specifically focussed on the appropriateness of endoscopy. Metabolic syndrome is accurately defined and the pivotal role of insulin resistance is emphasized. The strong relationship between GERD and metabolic syndrome has been pathophysiologically analyzed, taking into account the role of obesity, mechanical factors and metabolic changes. Data collected by our group regarding eating habits and GERD are briefly summarized at the end of a pathophysiological analysis. The literature on the subject strongly supports the possibility that lifestyle and eating habits may be involved in both GERD and metabolic syndrome in developed countries.

Infliximab therapy downregulation of basic fibroblast growth factor/syndecan 1 link: a possible molecular pathway of mucosal healing in ulcerative colitis

Background It is known that syndecan 1 in inflammatory bowel diseases is able to migrate from epithelial basolateral site to the stromal area and apical surface of epithelium with a consequent activation and modulation of basic fibroblast growth factor (bFGF), and this process sustains mucosal healing of ulcers. On the other hand, tumour necrosis factor (TNF) α mucosal levels are directly related to the entity of the damage in these disorders. Aim of the study A ‘post-hoc’ retrospective study was performed to estimate mucosal TNF α in rectal biopsies of subjects with ulcerative colitis (UC) before and after effective infliximab therapy and its relationship with syndecan 1, bFGF and endoscopic mucosal healing. Material and methods Paraffin-embedded rectal samples from 12 patients with UC responders to infliximab were analysed for TNF α, syndecan 1 and bFGF before and 6 months after therapy using a real-time reverse transcriptase polymersase chain reaction. Additionally, syndecan 1 location was evaluated by immunohistochemistry. Samples from 12 subjects with irritable bowel symptoms without endoscopic/histological abnormalities represented the control group. Mucosal healing induced by the treatment was defined by an endoscopic Mayo subscore changing from 2–3 to 0. ANOVA plus Student–Newman–Keuls was used for statistical analysis. Results The authors found that in the active disease, an increase in TNF α (p<0.001) is accompanied by raised levels of both syndecan 1 (p<0.005) and bFGF (p<0.005) compared with the control group. Infliximab-induced TNF α decrease to levels similar to controls is associated with both endoscopic mucosal healing and adhesion molecule/growth factor significant reduction. Additionally, syndecan 1 location, which is predominant in the stromal cells and apical epithelium in the active disorder, is quite exclusively located at the basolateral epithelial area in both healed mucosa and controls. Conclusions Balanced interaction among TNF α inhibition by infliximab, syndecan 1 migration, bFGF repair modulation and final adhesion molecule reversal to its normal location might represent a suitable molecular pathway of endoscopic mucosal healing in UC.

From chronic liver disorders to hepatocellular carcinoma: Molecular and genetic pathways

Hepatocarcinogenesis is a process attributed to progressive genomic changes that alter the hepatocellular phenotype producing cellular intermediates that evolve into hepatocellular carcinoma (HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and these conditions induce liver regeneration with accelerated hepatocyte cycling in an organ that is otherwise proliferatively at rest. Hepatocyte regeneration is accelerated by upregulation of mitogenic pathways involving molecular and genetic mechanisms. Hepatic growth factors, inhibitors and triggers may also play a role. This process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomerase re-expression, microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and the emergence of HCC are associated with the accumulation of irreversible structural alterations in genes and chromosomes even if the genomic basis of the malignant phenotype is largely heterogeneous. Therefore, a malignant hepatocyte phenotype may be produced by changes in genes acting through different regulatory pathways, thus producing several molecular variants of HCC. On these bases, a key point for future research will be to determine whether the deletions are specific, due to particular loci in the minimally deleted regions of affected chromosome arms, or whether they are non-specific with loss of large portions of chromosomes or entire chromosome arms leading to passive deletion of loci. The final aim is the possibility of identifying a step where carcinogenetic processes could be terminated.

OC.03.6 INFLIXIMAB THERAPY DOWNREGULATION OF BASIC FIBROBLAST GROWTH FACTOR/SYNDECAN 1 LINK: A POSSIBLE MOLECULAR PATHWAY OF MUCOSAL HEALING IN ULCERATIVE COLITIS

Background It is known that syndecan 1 in inflammatory bowel diseases is able to migrate from epithelial basolateral site to the stromal area and apical surface of epithelium with a consequent activation and modulation of basic fibroblast growth factor (bFGF), and this process sustains mucosal healing of ulcers. On the other hand, tumour necrosis factor (TNF) a mucosal levels are directly related to the entity of the damage in these disorders. Aim of the study A ‘post-hoc’ retrospective study was performed to estimate mucosal TNF a in rectal biopsies of subjects with ulcerative colitis (UC) before and after effective infliximab therapy and its relationship with syndecan 1, bFGF and endoscopic mucosal healing. Material and methods Paraffin-embedded rectal samples from 12 patients with UC responders to infliximab were analysed for TNF a, syndecan 1 and bFGF before and 6 months after therapy using a real-time reverse transcriptase polymersase chain reaction. Additionally, syndecan 1 location was evaluated by immunohistochemistry. Samples from 12 subjects with irritable bowel symptoms without endoscopic/ histological abnormalities represented the control group. Mucosal healing induced by the treatment was defined by an endoscopic Mayo subscore changing from 2e 3t o 0. ANOVA plus StudenteNewmaneKeuls was used for statistical analysis. Results The authors found that in the active disease, an increase in TNF a (p<0.001) is accompanied by raised levels of either syndecan 1 (p<0.005) and bFGF (p<0.005) compared with the control group 1