Gastroenterology and Hepatology from Bed to Bench

Inflammation can lead to malabsorption of important micronutrients such as iron. Malabsorption and nutritional deficiency can be caused by a variety of pathological and environmental factors causing a range of other symptoms commonly caused by both H. pylori infection and coeliac disease (CD). National guidelines suggest the routine taking of duodenal biopsies to exclude CD when investigating patients for iron deficiency anemia (IDA). Studies suggest that in absence of positive antibodies, IDA is rarely caused by CD. Recent British Society of Gastroenterology guidelines discourage the routine duodenal biopsies in low risk cases but despite this guidance, taking duodenal biopsies for IDA is a common practice. Many studies have reported that H. pylori infection is associated with IDA even in patients with CD. In countries with low H. pylori prevalence we still detect more H. pylori than CD standing behind IDA. Despite the strong association between IDA and H. pylori, taking biopsies to diagnose H. pylori infection is not usually a routine part of the diagnostic workup to identify the etiology of IDA. In this review we will discuss the impact of H. pylori in IDA and highlight the possible gaps in identifying the IDA etiology.

Keywords: Helicobacter pylori, Iron deficiency anaemia, Coeliac disease.

(Please cite as: Rostami-NejadM, AldulaimiD, LivettH, RostamiK. H.pylori associated with iron deficiency anemia; strongly evidence based but weakly reflected in practice. Gastroenterol Hepatol Bed Bench 2015;8(3):178-182).

Background and Objectives:

Survival models are statistical technique to estimate or predict the overall time up to specific events. Prediction is important in medical science and the accuracy of prediction is determined by a measurement, generally based on loss functions, called prediction error. The aim of this study is using parametric models to determine the factors influencing predicted survival time for patients with colorectal cancer (CRC) and select the best model by predicting error’s technique.

Materials and Methods:

600 colorectal cancer patients whom admitted to the Cancer Registry Center of Gastroenterology and Liver Disease Research Center, Taleghani Hospital, Tehran, who were followed at least for 5 years and have completed information selected for this study. Body Mass Index (BMI), Sex, family history of CRC, tumor site, stage of disease and histology of tumor included in the analysis. The survival time was compared by the Log-rank test and multivariate analysis was carried out using parametric. For selecting the best model, the prediction error by apparent loss was used.

Result:

Log rank test showed better survival for females, BMI more than 25, patients with early stage at diagnosis and patients with colon tumor site. Prediction error by apparent loss was estimated indicated that Weibull model was the best one for multivariate analysis. BMI and Stage were independent prognostic factors according to Weibull model.

Conclusion:

In this study, Weibull regression showed a better fit according to prediction error. Prediction error would be a criterion to select the best model with ability to make prediction of prognostic factors in survival analysis.

Cellsderived from Wharton’s jelly have been reported to display a wide multilineagedifferentiation potential, showing some similarities to both embryonic (ESC)and mesenchymal stem cells (MSCs). The present study investigated thedifferentiation potential of human Umbilical Cord Mesenchymal Stem Cells(UCMSCs) into hepatic lineage through embryonic body- like aggregates formationin the presence of IGF-I.HumanMSCs were isolated from the umbilical cord and characterized by flow cytometry;then, their ability to differentiate into osteogenic and adipogenic lineageswas verified. UCMSCs were plated in 20 ?L micro drops. After 3 days, 3Dspheroids were cultured on the gelatinized culture plates. A two-stepsdifferentiation protocol was used and the cell aggregates were exposed to themedia supplemented with IGF, HGF, oncostatin M, and dexamethasone for 21 days.Immunoperoxidase and immuno-fluorescence were performed for cyrokeratin 18, 19and albumin. Functional assays were done by periodic acid Schiff (PAS) andindocyanine green.  Thecells derived from 3D spheroids showed a polygonal shape after being exposed tohepatogenic media. Immunostaining demonstrated the expression of cytokeratin-18,19 and albumin by the differentiated cells. Besides, PAS staining revealedglycogen storage in differentiated cells. Also a greater number of large sizedifferentiated cells were found at the periphery of the expanded cellaggregates.Weestablished a protocol for UCMSCs differentiation into hepatocytes and thesecells were morphologically and functionally similar to hepatocytes. Thus,Hepatocyte differentiation may be facilitated by UCMSCs aggregate formationbefore administration of the differentiation protocols.

Aim: Since there is no effective therapy for PSC except for liver transplantation, we aimed to identify PSC predisposing factors to prevent IBD progression to PSC.

Background: Inflammatory bowel disease (IBD) is commonly associated with primary sclerosing cholangitis (PSC).

Patients and Methods: This retrospective study was conducted on 447 IBD patients from IBD Clinics of Ghaem and Emam Reza Hospitals. The data were collected by interview and from patient’s recorded medical files. Patients were divided into IBD-PSC group and those without PSC. Variables were compared between two groups and those with statistically significant differences in IBD-PSC group were considered as predictive factors for development of PSC. Results: The Frequency of PSC in IBD patients was 4.3% and all of the PSC patients had UC. The mean age of patients with PSC and UC were 39.1±11.33 and 38.7±13.4 years. The male to female proportion in PSC patients was 3.8:1 and in IBD patients was 0.9:1. There were statistically significant associations among PSC with gender, IBD duration and UC extension, mucocutaneous involvement, OCP consumption, history of surgery and history of PSC in the first- degree relatives.

Conclusion: PSC frequency among IBD patients in north-east of Iran was 4.3%. Statistically significant associations were found among PSC with gender, IBD duration, UC extension, mucocutaneous involvement, and history of surgery and history of PSC in the first- degree relatives and OCP consumption. It’s recommended to limit OCP consumption in IBD patients. Identification, modification of probable predisposing risk factors and early diagnosis of PSC is necessary.

Aim: The aims of this study were to determine the phylogenetic groups and investigate phenotypic and genotypic of ESBL and MBL-producing E. coli isolates from patients with diar­rhea in Kerman, southeast of Iran.

Background: Escherichia coli is detected as a significant cause of sporadic and outbreaks of diarrhea. The emergence of extended-spectrum ?-lactamases (ESBLs) and Metallo-?-lactamases (MBLs)-producing Escherichia coli caused problems in antibiotic treatments. E. coli strains can be assigned to four main phylogenetic groups, A, B1, B2 and D.

Patients and methods: Two hundred sixteen E. coli isolates were obtained from diarrheal patients between June to December 2013. Screening and confirmation tests of ESBLs and MBLs were done by disk-diffusion and broth micro-dilution methods according to CLSI 2013. The ESBL-positive isolates were screened to determine the phylogenetic groups and presence of bla_CTX-M-15, bla_OXA-1, bla_PER-1, bla_VIMand bla_IMP genes by PCR.

Results: In this study, From the 216 E. coli isolates 56 ESBL-positive isolates were detected. Among ESBL-positive isolates, 51 isolates were positive for bla_CTX-M-15 and one isolate were positive for both bla_CTX-M-15 and bla_OXA-1 genes. None of isolates were positive for bla_PER-1, bla_VIMand bla_IMP genes. PCR assays for phylotyping of diarrhea isolates indicated that the isolates were belonged to group A (54.16%), B1 (11.11%), B2 (12.96%) and D (21.75%). ESBL-positive isolates mostly distributed in phylo-groups A and D. The isolates possessed bla_CTX-M-15 gene were belonged to A (35 isolates), B1 (5), B2 (3) and D (8) phylo-groups. According to the antimicrobial susceptibility results, imipenem was found to be the most active agent, while resistance to cefotaxime was high.

Conclusion: Our results indicate that bla_CTX-M-15 gene is widespread among diarrhea. ESBL-producing E. coli isolates were dissemination among diversity of phylo-groups. The adequate infection control measures are essential to prevent further dissemination of ?-lactamases and MBLs in our country.

Aim: This study is aimed to elicit the possible correlation between breast and colon cancer from molecular prospectiveby analyzing and comparing pathway-based biomarkers.Background: Breast and colon cancer are known to be frequent causes of morbidity and mortality in men and womenaround the world. There is some evidence that while the incident of breast cancer in young women is high, it is reportedlower in the aged women. In fact, aged women are more prone to colorectal cancer than older men. . In addition, manystudies showed that several biomarkers are common among these malignancies.Patients and methods: The genes were retrieved and compared from KEGG database and WikiPathway, and subsequently,protein-protein interaction (PPI) network was constructed and analyzed using Cytoscape v:3.2.1 software and related algorithms.Results: More than forty common genes were identified among these malignancies; however, by pathways comparison,twenty genes are related to both breast and colon cancer. Centrality and cluster screening identified hub genes, includingSMAD2, SMAD3, (SMAD4, MYC), JUN, BAD, TP53. These seven genes are enriched in regulation of transforminggrowth factor beta receptor signaling pathway, positive regulation of Rac protein signal transduction, positive regulationof mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway, and positive regulation ofmitotic metaphase/anaphase transition respectively.Conclusion: As there are numerous genes frequent between colorectal cancer and breast cancer, there may be a commonmolecular origin for these malignancies occurrences. It seems that breast cancer in females interferes with the rate ofcolorectal cancer incidence.Keywords: Colon cancer, Breast cancer, Protein-Protein Interaction Network, Gene ontology.(Please cite as: Zamanian-Azodi M, Rezaei-Tavirani M, Rahmati-Rad S, Hasanzadeh H, Rezaei Tavirani M, SeyyediSS. Protein-Protein Interaction Network could reveal

Aim: The aims of this study were to characterize Iranian Shigella sonnei strains isolated from pediatric cases and evaluate the utility of multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for genotyping of local S. sonnei strains.

Background: S. sonnei has become the dominant species in certain parts of Iran. Although PFGE is still a gold standard for genotyping and source tracking of food-borne pathogens, it is laborious, expensive, time-consuming, and often difficult to interpret. However, MLVA is a PCR-based method, which is rapid, relatively inexpensive and easy to perform.

Patients and methods: A total of 47 S. sonnei isolates were obtained from sporadic cases of pediatric shigellosis in Tehran, Iran, during the years 2002-2003 (n=10) and 2008-2010 (n=37). The patients suffered from acute diarrhea and had evidence of more than three episodes of watery, loose, or bloody stools per day. A MLVA scheme based on 7 VNTR loci was established to assess the diversity of 47 S. sonnei isolates.

Results: Based on the results, it was clear that the S. sonnei isolates were heterogeneous. Overall, 47?S. sonnei isolates were discriminated into 21 different genotypes. Analysis of the MLVA profiles using a minimum spanning tree (MST) algorithm showed the usefulness of the MLVA assay in discriminating S. sonnei isolates collected over different time periods. However, no correlation was found between the MLVA genotypes and age, gender or clinical symptoms of the patients.

Conclusion: It is assumed that our S. sonnei isolates are derived from a limited number of clones that undergo minor genetic changes in the course of time. The present study has provided some valuable insights into the genetic relatedness of S. sonnei in Tehran, Iran.

Keywords: Shigella sonnei, multilocus variable-number tandem-repeat analysis, Iran.

(Please cite as: Ranjbar R, Memariani M. Multilocus variable-number tandem-repeat analysis for genotyping of Shigella sonnei strains isolated from pediatric patients. Gastroenterol Hepatol Bed Bench 2015;8(3):225-232).

Chronic Granulomatous Disease (CGD) is an inherited primary immunodeficiency disease which increases the body’ssusceptibility to infections caused by certain bacteria and fungi. CGD is a rare disease, caused by four genes, one type is 1Xlinked and the other three are “autosomal recessive”. Although clinical presentation is variable, but characteristic featuresare recurrent pneumonia, lymphadenitis, hepatic or other abscesses. Gastrointestinal tract symptoms are common in xlinkedrecessive form of CGD. These include gastric and esophageal obstruction and inflammatory bowel disease. GIinvolvement including small and large intestines, the findings of luminal narrowing and the presence of granuloma canmake it difficult to distinguish from Crohn’s disease. On the other hands according to the literature ulcerative colitis israrely reported in patients with CGD. Our case presented with ulcerative colitis with CGD.Keywords: Crohn’s disease, Chronic granulomatous disease, Ulcerative colitis.(Please cite as: Imanzade F, Sayarri A, Tajik P. Ulcerative colitis associated with chronic granulomatous disease:case report. Gastroenterol Hepatol Bed Bench 2015;8(3):233-235).

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