Showing papers in "Gastroenterology and hepatology from bed to bench in 2016"

Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases.

Abstract: Metabolome analysis is used to evaluate the characteristics and interactions of low molecular weight metabolites under a specific set of conditions. In cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH) the liver does not function thoroughly due to long-term damage. Unfortunately the early detection of cirrhosis, HCC, NAFLD and NASH is a clinical problem and determining a sensitive, specific and predictive novel method based on biomarker discovery is an important task. On the other hand, metabolomics has been reported as a new and powerful technology in biomarker discovery and dynamic field that cause global comprehension of system biology. In this review, it has been collected a heterogeneous set of metabolomics published studies to discovery of biomarkers in researches to introduce diagnostic biomarkers for early detection and the choice of patient-specific therapies.

Protein-protein interaction network analysis of cirrhosis liver disease

Abstract: Aim: Evaluation of biological characteristics of 13 identified proteins of patients with cirrhotic liver disease is the main aim of this research. Background: In clinical usage, liver biopsy remains the gold standard for diagnosis of hepatic fibrosis. Evaluation and confirmation of liver fibrosis stages and severity of chronic diseases require a precise and noninvasive biomarkers. Since the early detection of cirrhosis is a clinical problem, achieving a sensitive, specific and predictive novel method based on biomarkers is an important task. Methods: Essential analysis, such as gene ontology (GO) enrichment and protein-protein interactions (PPI) was undergone EXPASy, STRING Database and DAVID Bioinformatics Resources query. Results: Based on GO analysis, most of proteins are located in the endoplasmic reticulum lumen, intracellular organelle lumen, membrane-enclosed lumen, and extracellular region. The relevant molecular functions are actin binding, metal ion binding, cation binding and ion binding. Cell adhesion, biological adhesion, cellular amino acid derivative, metabolic process and homeostatic process are the related processes. Protein-protein interaction network analysis introduced five proteins (fibroblast growth factor receptor 4, tropomyosin 4, tropomyosin 2 (beta), lectin, Lectin galactoside-binding soluble 3 binding protein and apolipoprotein A-I) as hub and bottleneck proteins. Conclusion: Our result indicates that regulation of lipid metabolism and cell survival are important biological processes involved in cirrhosis disease. More investigation of above mentioned proteins will provide a better understanding of cirrhosis disease.

An experimental model of colitis induced by dextran sulfate sodium from acute progresses to chronicity in C57BL/6: correlation between conditions of mice and the environment.

Abstract: Aim : To induce acute colitis progresses to chronicity in C57BL/6 mice by dextran sulfate sodium. Background : Murine models are essential tools to understand IBD pathogenesis. Among different types of chemically induced colitis models, the dextran sulfate sodium (DSS)-induced colitis model is the most common model of IBD, due to its simplicity. Patients and methods : Male C57BL/6 mice 6–8 weeks old, were collected and matched by age with controls. C57BL/6 mice treated with 2 cycles of 3.5% DSS for 4 days and 4 days of pure water between each cycle. After that, mice were sacrificed and the entire colon was removed. Small sections of the colon were fixed in formaldehyde, embedded in paraffin and sectioned with a microtome. Sections were stained with hematoxylin eosin to analyses the degree of inflammation. Results : After the first cycle oral administration of DSS, mice with severe and visible rectal bleeding and diarrhea entered into the acute phase. After day 4-5, bleeding and diarrhea were improved and mice entered into the chronic phase with peak levels of weight loss. Macroscopically, the inflammation was predominantly located in the distal colon. Microscopically, examination of the distal colon sections showed a decrease number of goblet cells, loss of crypts, signs of surface epithelial regeneration and moderate to severe infiltration of inflammatory cells in the mucosa. Conclusion : In order to achieve an experimental colitis model, our protocol is recommended for future therapies in IBD experimental modeling.

Protein-protein interaction network of celiac disease.

Abstract: Aim The aim of this study is to investigate the Protein-Protein Interaction Network of Celiac Disease. Background Celiac disease (CD) is an autoimmune disease with susceptibility of individuals to gluten of wheat, rye and barley. Understanding the molecular mechanisms and involved pathway may lead to the development of drug target discovery. The protein interaction network is one of the supportive fields to discover the pathogenesis biomarkers for celiac disease. Material and methods In the present study, we collected the articles that focused on the proteomic data in celiac disease. According to the gene expression investigations of these articles, 31 candidate proteins were selected for this study. The networks of related differentially expressed protein were explored using Cytoscape 3.3 and the PPI analysis methods such as MCODE and ClueGO. Results According to the network analysis Ubiquitin C, Heat shock protein 90kDa alpha (cytosolic and Grp94); class A, B and 1 member, Heat shock 70kDa protein, and protein 5 (glucose-regulated protein, 78kDa), T-complex, Chaperon in containing TCP1; subunit 7 (beta) and subunit 4 (delta) and subunit 2 (beta), have been introduced as hub-bottlnecks proteins. HSP90AA1, MKKS, EZR, HSPA14, APOB and CAD have been determined as seed proteins. Conclusion Chaperons have a bold presentation in curtail area in network therefore these key proteins beside the other hub-bottlneck proteins may be a suitable candidates biomarker panel for diagnosis, prognosis and treatment processes in celiac disease.

Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks.

Abstract: Aim: In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls. Background: Increased understanding of cancer biology has enabled identification of molecular events that lead to the discovery of numerous potential biomarkers in diseases. Protein-protein interaction networks is one of aspect that could elevate the understanding level of molecular events and protein connections that lead to the identification of genes and proteins associated with diseases. Methods: Gene expression data, including 63 gene or protein names for hepatocellular carcinoma and 29 gene or protein names for cirrhosis, were extracted from a number of previous investigations. The networks of related differentially expressed genes were explored using Cytoscape and the PPI analysis methods such as MCODE and ClueGO. Centrality and cluster screening identified hub genes, including APOE, TTR, CLU, and APOA1 in cirrhosis. Results: CLU and APOE belong to the regulation of positive regulation of neurofibrillary tangle assembly. HP and APOE involved in cellular oxidant detoxification. C4B and C4BP belong to the complement activation, classical pathway and acute inflammation response pathway. Also, it was reported TTR, TFRC, VWF, CLU, A2M, APOA1, CKAP5, ZNF648, CASP8, and HSP27 as hubs in HCC. In HCC, these include A2M that are corresponding to platelet degranulation, humoral immune response, and negative regulation of immune effector process. CLU belong to the reverse cholesterol transport, platelet degranulation and human immune response. APOA1 corresponds to the reverse cholesterol transport, platelet degranulation and humoral immune response, as well as negative regulation of immune effector process pathway. Conclusion: In conclusion, this study suggests that there is a common molecular relationship between cirrhosis and hepatocellular cancer that may help with identification of target molecules for early treatment that is essential in cancer therapy.

Survival rate of gastric cancer in Iran; a systematic review and meta-analysis.

Abstract: Aim : In this study, we aimed to estimate one- to five-year survival rates in Iranian patients with gastric cancer (GC). In addition, we preformed subgroup analyses and meta-regression to explore possible sources of heterogeneity between studies. Background : According to literatures, there has been increasing attention to the long-term survival rate in patients with GC in Iran. However, results have been inconsistent and remain controversial in overall survival rates. Patients and methods : Literature searches were conducted using PubMed, Scopus, and ISI, as well as Magiran, Medlib, SID, and Iran Medex databases. Studies were pooled and summary one to five survival rates were calculated. Univariate and multivariate regression analyses were used to explore possible sources of heterogeneity among studies. Subgroup analyses were also conducted. Analyses were conducted using the STATA statistical software package. Results : Final analysis of 29361 patients from 26 eligible studies was performed. The overall survival rate (one to five years) in all studies, by meta-analysis of 24, 14, 23, 12 and 22 studies were 52%, 31%, 24%, 22%, and 15%, respectively. Meta-regression analysis showed an increase in one- and five-year survival rate over the time (Reg Coef = 0.016, p= 0.04) and (Reg Coef= 0.021, p= 0.049), respectively. Positive heterogeneity was observed between quality of papers and data sources (P<0.001). Conclusion: More than half of GC deaths happened in the first year at diagnosis, and another 30% plus they occurred during the second year after confirmed diagnosis. Our results admit lower survival rates in Iran, similar to other developing countries.

Autoimmune enteropathy: not all flat mucosa mean coeliac disease.

Abstract: A 62-year-old woman complaining of severe malabsorption was diagnosed with celiac disease based on the findings of flat, small intestinal mucosa and HLA-DQ2 positivity, although celiac serology was negative. This diagnosis was questioned due to the lack of clinical and histological improvement after a long period of strict gluten-free diet. The detection of enterocyte autoantibodies guided to the correct diagnosis of autoimmune enteropathy, leading to a complete recovery of the patient following an appropriate immunosuppressive treatment. Autoimmune enteropathy should be considered in the differential diagnosis of malabsorption with severe villous atrophy, including those cases with negative celiac-related serology.

Celiac disease and obstetrical-gynecological contribution

Abstract: Celiac disease (CD) shows an increased prevalence in female, particularly during the fertile period. Celiac disease should be researched in infertility, spontaneous and recurrent abortions, delayed menarche, amenorrhea, early menopause, and children with low birth-weight. Celiac disease is still little considered during the evaluation of infertility. Up to 50% of women with untreated CD refer an experience of miscarriage or an unfavorable outcome of pregnancy. Celiac patients taking a normal diet (with gluten) have a shorter reproductive period. Women with undiagnosed CD had a higher risk of small for gestation age infants very small for gestational age infants and pre-term birth when compared with women with noted CD. The link between NCGS and infertility is actually unknown. The goal of our work is to perform an actual review about this topic and to increase the awareness in the medical population to research celiac disease in selected obstetric and gynecological disorders.

Dysbiosis of fecal microbiota and high frequency of Citrobacter, Klebsiella spp., and Actinomycetes in patients with irritable bowel syndrome and gastroenteritis.

Abstract: Aim This study was aimed to characterize putative differences of fecal microbiota between irritable bowel syndrome (IBS) and gastroenteritis patients and healthy controls Background New evidence proposed that gut microbiota has a deep effect on the balance between health and disease Patients and methods The presence of Clostridium difficile, Campylobacter spp, Enterobacteriacea and Staphylococci were detected in the samples using selective and specific culture media Microscopic examination of the samples was done to detect Actinomycetes, yeasts, Bifidobacteria, Fusobacterium spp, as well as white blood cells, red blood cells, mucus and epithelial cells Results Results of this study showed relatively higher frequency of Citrobacter spp, Lactobacilli, and Actinomycetes in the IBS patients Elevated levels of WBC, RBC secretion, and increased amounts of Klebsiella, Escherichia coli and Citrobacter spp were characterized in the patients with gastroenteritis compared with the control group Conclusion Depletion of gram positive cocci and gram negative bacilli also suggested dysbiosis of intestinal microbiota in these patients

Helicobacter pylori CagA induced interleukin-8 secretion in gastric epithelial cells.

Abstract: Aim: Since, contradictory data have been reported about the effect of diverse variants of H. pylori virulence factors on IL-8 induction, we aimed to analyze the effect of this diversity on levels of IL-8 secretion in AGS cell line. Background: Helicobacter pylori colonizes the human stomach and induces the activation of inflammatory cytokines, including interleukin (IL)-8, in the gastric mucosa. This induction promotes neutrophil and monocyte recruitment that causes gastric tissue damage. Methods: To determine whether different strains of H. pylori and their CagA variants have possible roles on IL-8 induction, polarized AGS cell line was infected with CagA+ H. pylori strains carrying different EPIYA motifs (ABCCC and ABC) and CagA- strain for 24 hours. Difference in stimulation of IL-8 was measured by ELISA. Results: IL-8 secretion was elevated in the treated cells with CagA encoding strains compared with the negative one. Furthermore, a noticeably increased level of IL-8 induction was measured by the CagA -EPIYA type ABCCC encoding strain in compare to that carried EPIYA type ABC Conclusion: Results of this study provide new evidence about different effects of H. pylori strains and possible roles of their CagA variants on IL-8 induction. It seems that not only carriage of cagA and its expression, but also diversity in EPIYA motif be involved in IL-8 induction in the gastric epithelial cells.

Comparison of three methods for mitochondria isolation from the human liver cell line (HepG2)

Abstract: Aim : The aim of this study was to evaluate and compare three available methods for mitochondrial isolation from a human cell line to predict the best method for each probable application. Background : Organelle isolation is gaining importance in experimental laboratory settings. Mitochondrial dysfunction may affect tumorgenesis process. There are some evidences that transplantation of healthy, intact and active mitochondria into cells containing defective mitochondria may reduce the proliferation. Therefore, isolated mitochondria could be considered as an effective tool for assessment and management of mitochondrial related disorders. Patients and methods : Mitochondrial isolation from the human liver cell line ( HepG2 ) was performed using two commercially available kits, including Qproteome (Qiagen) and MITOISO2 (Sigma-Aldrich), as well as a manual method. Integrity of inner membrane of mitochondria was assessed by JC-1 staining. Activity of isolated mitochondria was evaluated by DCFH-DA staining, and total yield of isolated mitochondria determined by micro-Lowry method. Finally, relative quantification using Real-time PCR was conducted to compare the mtDNA copy number of mitochondria isolated by three different methods. Results : Compared to other methods, manual kit resulted in higher yields of total amount of mitochondrial protein and mtDNA copy numbers. Isolated mitochondria by Qproteome kit, showed a higher activity. Finally, the integrity of inner-membrane of isolated mitochondria was significantly higher in Qproteome when compared with the other two methods. Conclusion : Due to differences in quality, quantity and activity of isolated mitochondria using three techniques discussed here, the method in which best-suited to each research project should be selected according to the distinct features of isolated mitochondria.

Postoperative pain relief after laparoscopic cholecystectomy: intraperitoneal sodium bicarbonate versus normal saline.

Abstract: Aim: The aim of this study was to determine the effect of sodium bicarbonate irrigation versus normal saline irrigation in patients undergoing a laparoscopic cholecystectomy. Background: Pain in patients undergoing laparoscopic cholecystectomy is the most common complaint, especially in the abdomen, back, and shoulder region.Patients and methods: In a double blind randomized clinical trial, 150 patients were assigned to the three groups (50 patients in each group). Group A received intraperitoneal irrigation normal saline (NS). Groups B and C received irrigation sodium bicarbonate and none irrigation, respectively. Pain was assessed using a visual analog scale (VAS) for 6, 18 and 24 hours postoperatively, as well as one week after the surgery. Data analysis was performed using SPSS ver18 and chi-square, Fisher’s Exact Test, on-way ANOVA and repeated measure ANOVA tests.Results: Patients in groups showed no significant difference in terms of age, gender, past medical history and smoking history (p>0.05). Left shoulder tip pain was significantly lower only between the sodium bicarbonate group and non-washing group at 6, 18, and 24 hours postoperatively (P=0.04, P=0.02 and P=0.009 respectively). There was no significant difference between the three treatment groups in right shoulder tip pain, back pain and port site incisional pain.Conclusion: In laparoscopic cholecystectomy, peritoneal irrigation with sodium bicarbonate may reduce the intensity of postoperative shoulder tip pain and is an effective method for improving the quality of life within the early recovery period.

Molecular diagnosis and anti-microbial resistance patterns among Shigella spp. isolated from patients with diarrhea.

Abstract: Aim : This study aims to determine the serogroup distribution and molecular diagnosis, as well as antimicrobial resistance profiles among Shigella spp. isolated from patients with diarrhea in Kerman, southeast of Iran. Background : Shigella species are frequent cause of bacterial dysentery worldwide. Previous studies have been reported that S. sonnei and S. flexneri are the most prevalent serogroups in various parts of Iran. Patients and methods : A total of 624 stool samples were randomly collected from patients with diarrhea from June 2013 to August 2014. Biochemical and serological characterizations were performed for identifying Shigella spp. In addition, the multiplex PCR assay was carried out for the detection and differentiation of three pathogenic Shigella spp. Antibiotic susceptibility testing was performed according to the Clinical Laboratory Standards Institute (CLSI) guidelines. Results : Fifty six (9%) Shigella strains were isolated from stool samples. The most common species were S. flexneri 31(55.4%), followed by S . sonnei 18(32.1%) and S. boydii 7(12.5%). S. dysentery was not detected in the present study. All the isolates that identified by serological test as Shigella spp. were confirmed by the multiplex PCR method. The highest rate of resistance was observed for ampicillin and trimethoprim-sulphamethoxazole antibiotics with 52(92.9%) resistant, followed by tetracycline 44(78.6%) and cefotaxime 33(58.9%). All Shigella isolates were susceptible to ciprofloxacin. A significant relationship was found between the Shigella species and cefotaxime resistance ( p <0.05). Conclusion : S. flexneri was found as the most prevalent serogroup causing shigellosis. The high rate of resistance to third-generation cephalosporins limits the treatment options available for the management of shigellosis in Kerman, Iran.

Introduction of inflammatory bowel disease biomarkers panel using protein-protein interaction (PPI) network analysis.

Abstract: Aim: In the present study, a protein-protein interaction network construction is conducted for IBD. Background: Inflammatory bowel diseases as serious chronic gastrointestinal disorders attracted many molecular investigations. Diverse molecular information is present for IBD. However, these molecular findings are not highlighted based on interactome analysis. On the other hand, PPI network analysis is a powerful method for study of molecular interactions in the protein level that provide useful information for highlighting the desired key proteins. Methods: Cytoscape is the used software with its plug-ins for detailed analysis. Two centrality parameters including degree and betweenness are determined and the crucial proteins based on these parameters are introduced. Results: The 75 proteins among 100 initial proteins are included in the network of IBD. Seventy-five nodes and 260 edges constructed the network as a scale free network. The findings indicate that there are seven hub-bottleneck proteins in the IBD network. Conclusion: More examination revealed the essential roles of these key proteins in the integrity of the network. Finally, the indicator panel including NFKB1, CD40, TNFA, TYK2, NOD2, IL23R, and STAT3 is presented as a possible molecular index for IBD. Keywords: Inflammatory bowel diseases (IBD), Protein-protein interaction (PPI) network analysis, Hub-bottlenecks, Protein clusters

Distribution and risk factors associated with intestinal parasite infections among children with gastrointestinal disorders.

Abstract: Aim: Prevalence and risk factors associated with intestinal parasites among children ? 12 years old in Nahavand county western Iran, was the objective of this search. Background: Intestinal parasites (IPs) are important health problems among most societies. Methods: This cross sectional study was carried out during 6 months from April to September 2014 in Nahavand County western Iran. Fecal samples were collected from 500 children suffering from gastrointestinal disorders (GIDs) and examined by macroscopy and microscopic (using saline and iodine wet mount, formalin-ether sedimentation, Trichrome and modified Ziehl Neelsen staining) methods. Finally, data was analyzed using Chi-square (Chi2) test and Fisher’s exact test as well as logistic regression. Results: 21.8% (109/500) of the samples were infected by one or more IPs. The most common parasites were Blastocystis sp. (16.2%), followed by Cryptosporidium spp. (2.6%), Giardia lamblia (1.6%), and Entamoeba coli (1.6%). Prevalence of intestinal parasite infections were significantly associated with age (OR= 2.280; CI 95% = 1.375-3.830; P<0.002), gender (OR= 0551; CI 95% = 0.348-0.875; P<0.011), contact with domestic animal or soil (OR= 0.492; CI 95% = 0.282-0.860; P<0.013) and seasons (OR= 2.012; CI 95% = 1.254-3.227; P<0.004). There was a significant correlation between IPs with diarrhea (OR= 3.027; CI 95% = 1.712-5.345; P<0.001) and nausea or vomiting (OR= 3.261; CI 95% = 1.281-8.175; P<0.013). Conclusion: Blastocystis sp. was the most prevalent parasites among children in Nahavand County and Helminthes infection have been dramatically decreased. Our finding shown that gender, age, season and contact with domestic animals or soil polluted are main predictive factors for intestinal parasite infections among children in this region. Moreover, IPs infection among children with gastrointestinal disorders were significantly associated with diarrhea and vomiting or nausea signs.

Prevalence of intestinal parasites in referred individuals to the medical centers of Tonekabon city, Mazandaran province.

Abstract: Aim: The aim of the present study was to determine the prevalence of intestinal parasites and their relation with socio-demographic data in referred individuals to the medical centers in Tonekabon, Mazandaran province, 2015. Background: Due to the climatic and ecological conditions in Mazandaran province, determination of the status of intestinal parasites among referred individuals to the medical centers of Tonekabon city can help researchers and healthcare services to prevent and/or control of parasitic infection in this region. Methods: This cross sectional study was conducted with randomized sampling in 2015 on 820 stool samples. Stool samples were assessed using direct slide smear with saline and Lugol, formalin-ether concentration, Ziehl-Neelsen and trichrome staining. Polymerase Chain Reaction (PCR) using specific primers was conducted for the samples suspected for Entamoeba histolytica/E. dispar and Cryptosporidium spp. One Cryptosporidium positive sample in this study was submitted for sequencing. Results: A total of 444 (54.1%) and 376 (45.9%) were male and female, respectively. Furthermore, 495 (60.4%) and 325 (39.6%) of participants had lived in the urban and rural areas, respectively. Overall, 222 participants (27.1%) were infected with at least one intestinal parasites. Prevalence of pathogenic protozoa ( Giardia lamblia and Cryptosporidium spp.) and helminthes parasites was calculated as 3.1 and 1.2%, respectively. The most common intestinal parasites in this area were: Blastocystis 153 (18.7%), Endolymax nana 44 (5.4%), Entamoeba coli 40 (4.9%), Giardia lamblia 25 (3%), Iodamoeba butschlii 22 (2.7%), Ascaris 5 (0.6%), Enterobius vermicularis 4 (0.5%), Trichostrongylus 1 (0.1%) and Cryptosporidium 1 (0.1%). By sequencing of the positive Cryptosporidium isolate using Gp60 gene, Cryptosporidium parvum subtype ?aA16G2R1 was diagnosed. Conclusion : Protozoa were more abundant than helminthes and Giardia lamblia was the most common protozoan pathogen. In this study, no significant association was found between the prevalence and the variables of socio-demographic data. Adequate knowledge and periodic surveillance of the prevalence of parasites and the socio-demographic variables that affect their frequency is important for effective control of parasitic infections.

Cancer stem cells CD133 and CD24 in colorectal cancers in Northern Iran.

Abstract: Aim : We aimed to study the expression of CD24 and CD133 in colorectal cancer and normal adjacent tissues to assess a relationship between these markers and clinic-pathological characteristics and patient’s survival. Background : Cancer stem cells are a group of tumor cells that have regeneration and multi-order differentiation capabilities. Patients and methods : Expression of CD24 and CD133 was studied in a paraffin block of colorectal cancer and normal tissues near tumors with the immuneohistochemical method in patients who were referred to Imam Khomeini Hospital in Sari. Results : A total of 50 samples (25 males and 25 females) with a mean age of 67.57±13.9 years old with range 28-93 years, included 3 mucinous carcinoma and 47 adenocarcinoma. Expression of CD133 marker was negative in 29 cases and positive in 21 cases. Expression of CD24 in tissue near tumor cells was found in 30% of available samples. The relationship between expressing CD24 with treatment (surgery and chemotherapy) was significant and its relationship with patient’s survival was insignificant statistically. However, there was a clear difference as mean survival age of patients based on CD24 expression was 26.64±18.15 for negative cases and 41.75±28.76 months for positive cases. CD24 and CD133 expressions and their co-expression with other clinic-pathological factors were not significant. Conclusion : During this study, the relationship between CD24 and treatment type was significant. To confirm this result, various studies with high sample numbers and other stem cell markers are recommended.

Cronkhite- Canada syndrome; a case report and review of the literature.

Abstract: Cronkhite- Canada syndrome (CCS) considered as a rare and non-hereditary disorder. Gastrointestinal polyposis and diarrhea along with some extra signs and symptoms such as hypoproteinemia, and epidermal manifestations are recognized in this syndrome. The pathophysiology of this syndrome is not completely understood and it seems that inflammatory processes may be involved. We present a 50 year-old man with hamartomatous polyps throughout the colon and long-lasting diarrhea not responding to typical therapies during three years.

Pregnancy with autoimmune hepatitis

Abstract: Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis patients. Background: There are only limited data describing pregnancy in patients with autoimmune hepatitis. Patients and methods: Retrospective analysis of pregnancies with autoimmune hepatitis followed in Centro Hospitalar do Porto, Portugal in the last ten years. Results: We reported nine pregnancies in seven patients with autoimmune hepatitis. Two patients had documented liver cirrhosis prior to the pregnancy. In this study, 66.7% of patients were treated with azathioprine and 88.9% with prednisolone. Clinical improvements were observed in 11.1% of pregnancies and 22.2% exacerbations were diagnosed. There were six live births and two preterm deliveries (preterm delivery rate of 33%). We also report three first trimester miscarriages (early gestation miscarriage rate of 33%). There were no neonatal or maternal deaths. Conclusion: The favorable obstetric outcome is a realistic expectation in patients with autoimmune hepatitis. Tight monitoring and control of asymptomatic and unpredictable exacerbations, which are unrelated to the severity of the underlying disease, are essential to the prognosis of the current pregnancy.

Development of systemic sclerosis in patients with autoimmune hepatitis: an emerging overlap syndrome.

Abstract: Aim: We described two case reports of AIH/SSc overlap syndrome and reviewed literatures regarding this issue. Background: AIH is a chronic hepatitis of unknown aetiology characterized by continuing hepatocellular necrosis and inflammation. AIH overlap syndromes have been reported with other autoimmune diseases. Patients and methods: According to the classification criteria for SSc, we conducted a retrospective chart review of 35 cases with biopsy-proven AIH over the past 5 years at our institution. We reviewed the MEDLINE database using the appropriate key-words. Results: A chart review of 35 cases (M/F ratio 1:2, mean age 47.6±10.3 years) revealed nine patients (9/35, 25.7%) with CTD (four males and three females with a mean age of 45.1±8.4 years). All patients had ANA. Four patients were SSA/Ro positive UCTD (1/35, 2.85%), and six patients developed SLE (6/35, 17.1%). Only two female patients (2/35, 5.7%) with specific SSc AAb developed a systemic sclerosis. We described a patient with AIH who was diagnosed with diffuse systemic sclerosis-sine scleroderma with positive anti-centromere B and SSA/Ro52 KDa antibodies. We also reported a patient with AIH who was diagnosed limited SSc with contemporary presence of anti-centromere A and anti-RNA polymerase III antibody. Conclusion: We suggest that SSc may be considered to be one of the manifestations associated with AIH. Patients with AIH may have an increased risk to develop SSc and should be followed, especially when Raynaud phenomenon was found.

Evaluation of antimicrobial susceptibility and integron carriage in Helicobacter pylori isolates from patients.

Abstract: Aim : The purpose of this study was to determine the antibiotic susceptibility pattern and distribution of integron in H. pylori isolates collected from patients referred to private health care centers in Tehran, Iran. Background : Antibiotic resistance is the main reason for failure of Helicobacter pylori therapy. Integrons as genetic reservoirs play main roles in the dissemination of antimicrobial resistance gene. Methods: During a 12-month cross-sectional study period, 65 H. pylori isolates were recovered from 124 biopsy specimens. Isolates were subjected to susceptibility testing using by Epsilometer test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PCR was used to detect different types of integrons. Results: Antimicrobial susceptibility testing revealed that 73.8% of isolates were resistant to metronidazole, 43.1% to clarithromycin, 29.2% to tetracycline, 27.7% to amoxicillin, 23.1% to rifampicin and 13.4% to levofloxacin. Frequency of multidrug resistance among H. pylori isolates was 26.1%. The most predominant resistance profiles among our isolates were included resistance to clarithromycin and metronidazole (20%). Class 1 and 2 integrons were detected in 8 (12.3%) and 15 (23.1%) of the isolates, respectively. Conclusions: The high prevalence of multidrug resistance and frequency of class 2 integron in this survey can be a warning for clinicians. Continuous surveillance is necessary for the development of new treatment protocols to prevent the treatment failures and also further spread of resistant isolates.

The likelihood ratio and frequency of DQ2/DQ8 haplotypes in Iranian patients with celiac disease

Abstract: Aim: The aim of this study was to evaluate the likelihood ratio and frequency of DQ2 and DQ8 in Iranian patients with celiac disease (CD).Background: The HLA DQ2 and HLA DQ8 are the important mediators in the development of celiac disease. A few studies evaluated the frequency of HLA DQ2 and HLA DQ8 haplotypes among the Iranian population with low sample size.Patients and methods: In this cross-sectional study, to predict HLA–DQ2 and DQ8 haplotypes, 141(73 male, 78 female) confirmed CD patients compared to 151 healthy controls were enrolled into this study during 2013-2014. HLA DQ2/ DQ8 haplotypes was determined in cases and controls using PCR-SSP technique.Results: DQ2 and DQ8 were positive in 80% (n=111) and 49% (n= 69) of CD patients and 36% (n=61) and 13% (n=21) of control group respectively. Moreover, 32% (n=45) of CD patients and 5.3% (n=8) of the control group were carrier of both haplotypes. In the case group about one-third of patients (32.2%) were positive for carrying both DQ2 and DQ8 heterodimers while only 5.3% (n=8) of the control group were carrier. In addition, the positive likelihood ratio of DQ2 and DQ8 were 1.74 (CI: 1.4- 2.1), and 2.6 (CI: 1.8– 2.7), respectively.Conclusion: The result of this study showed that the frequency of DQ8 among our population is higher than those reported by European countries, but it is close to those founded in South America and Middle East. This result suggests that the higher prevalence of HLA DQ8 pattern in Iranian CD patients is similar to non-European patients

An unusual cause of anemia in cirrhosis: spur cell anemia, a case report with review of literature.

Abstract: Chronic anemia is common in liver cirrhosis. In this setting, the pathogenesis of anemia is complex and multifactorial. Spur cell anemia is a serious disorder in cirrhotic patients and is associated with poor prognosis. Liver transplantation constitutes the only therapeutic tool. We report a case with severe spur cell anemia in alcoholic liver cirrhosis. In the attempt to investigate the origin of the disorder, we have evaluated the lipoprotein profile and found a significant reduction of apolipoprotein AI and HDL3 subclass as a possible cause of the disease.

Changes in portal blood flow and liver functions in cirrhotics during Ramadan fasting in the summer; a pilot study.

Abstract: Aim: Assessment of short term changes in portal blood flow and long term changes in liver functions in cirrhotic patients who chose to fast during the month of Ramadan in summer.Background: During Ramadan, healthy Muslims obligated to fast from predawn to sunset.Patients and methods: Forty cirrhotic patients intended to fast during the month of Ramadan in the year 2014, were examined by Congestion index (CI) as a non-invasive indicator of short term changes in the portal blood flow, while liver function tests were determined as an indicator of long term changes in liver functions.Results: A total of 38 patients completed the whole month fasting and two patients discontinued fasting due to variceal bleeding. The complicated patients were 7. CI showed a statistically significant increase from fasting to postprandial status (P <0.001), with statistically significant increases from fasting to postprandial status in Child class A (P <0.001), and B (P <0.001). We did not find a statistical significance between patients with complications and those without complications (P = 0.6). There was a statistically significant rise in the serum bilirubin after Ramadan. Deterioration noticed as advanced Child classes, development of lower limb edema, increasing ascites, increasing jaundice and overt encephalopathy.Conclusion: Cirrhotic patients showed significant short-term changes in the portal blood flow. However, these changes are not linked to complications or deterioration of liver functions and accommodated especially in patients with Child class A and B. Child class C patients should not fast.

Evaluation of hepatitis C virus intrafamilial transmission among families with one index case, a pilot study from Fars province, Iran.

Abstract: Aim: Our aim was to survey the rate and risk factors for Hepatitis C virus interfamilial transmission among families with one index case. Background: The role of intrafamilial transmission in Hepatitis C virus epidemiology is still debated. Patients and methods: A cross-sectional study was conducted on 34 families (236 members) of HCV infected patients from Fars province, spring to summer 2013. All subjects were first evaluated for the risk factors of exposure and then their serum was checked for the presence of HCV antibody and the genome, using ELISA and PCR. The genotype of all PCR positive cases was also determined by a commercial assay. Two independent sample t test and Chi-Square test were used to compare groups together. Results: In 18 out of 34 families, HCV antibody was detected (52.9%) in new members. Among them, HCV transmission in 11 families (32%) was also confirmed by PCR. Having a history of intravenous drug abuse (P=0.006) and incarceration (P=0.01) showed to be important risk factors for interfamilial transmission. Hence, blade/needle sharing (P=0.016) just following molecular assay and sex (P=036) only in the serologic analysis were also determined as significant risk factors. Furthermore, based on serologic results, medium socioeconomic state was further associated with this manner of transmission (P=0.019 and P=0.328). Interestingly, among relatives, 13 cases were brothers while just 5 cases were couples. The genotypes 3a and 1a were more prevalent among the population. Conclusion: In conclusion, our finding highlighted a noticeable role of interfamilial transmission for HCV spread and supports the significant role of close relatives, especially brother relationship in this spread. Hence, the socioeconomic state was associated with the transmission rate of virus in the family.

Seroprevalence of hepatitis a virus among iranian soldiers

Abstract: Aim: This study aims to investigate the seroprevalence of HAV immunity among Iranian soldiers and determine whether vaccination should be given to military draftees. Background: Hepatitis A virus (HAV) is highly contagious in individuals living in crowded conditions such as military centers. To the best of our knowledge, there are limited data about HAV prevalence among Iranian soldiers. Patients and methods: In this cross-sectional study, a total of 1554 soldiers were recruited through a random clustering sampling. Serum anti-HAV antibody was measured by Enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using SPSS. Results: A total of 1554 male soldiers with age ranged from 18 to 34 years (mean age: 21.2±1.9 years) at baseline were evaluated. Overall, 80.3% of the analyzed specimens were anti-HAV seropositive. Seroprevalence rates significantly increased with the age. Conclusion: Our results suggest that vaccination for HAV is not necessary for Iranian military draftees. However, the vaccination is recommended for high-risk groups, including anti-HAV seronegative soldiers.

Mesenchymal stem cells as potential therapeutic approaches in celiac disease

Abstract: As a chronic immune complication, celiac disease has a broad spectrum of clinical manifestations and gluten ingestion as an external trigger will induce the onset of this disease in genetically predisposed individuals. Because of the complex nature of celiac disease and various cascades of immunological pathways, therapies which are tend to target a single pathway or factor, often have unsatisfactory results. Thus, it should be considered that the new emerging area of cellular therapy by targeting multiple pathways may hold the key for treating celiac affected patients with complicated forms of this disease. The aim of this review is to discuss different pathways which are affected by celiac disease and to compare how various strategies, mainly cellular therapies, can regulate these pathways.

First report of Tasmanian sheep strain (G2) genotype isolated from Iranian goat using the high resolution melting (HRM) analysis.

Abstract: Aim: The present study was aimed to evaluate E. granulosus genotypes isolated from goats using HRM analysis in Isfahan province. Background: Cystic echincoccosis, so-called hydatidosis, is widespread infection caused by the larval stage of Echinococcus granulosus . This is an important zoonotic disease worldwide, especially in the developing countries such as Iran. To date, molecular studies mainly based on the mitochondrial DNA sequences have identified distinct genotypes termed G1-G10 which can differ in some characteristics such as the growth and infectivity to different intermediate hosts or the survival rate in the definitive hosts that are important for the development of control strategies. Methods: From August to December 2014, 1341 goats were investigated and hydatid cysts were collected from the liver and lungs of 43 infected goats in Isfahan province abattoirs, Isfahan, Iran. Total genomic DNA was extracted from each sample, amplified for the presence of polymorphism of mitochondrial gene coding for cytochrome c oxidase subunit 1 (CO1), using high resolution melting curve (HRM) method. Results: the results of HRM analysis using the sequence of CO1 gene for 43 Echinococcus granulosus isolates from goats showed 31, 2 and 10 isolates were identified as G1, G2, and G3 genotypes, respectively. Conclusion: G1 is the predominant genotype in the isolated goat samples in Isfahan province, and the presence of G2 strain was reported for the first time in goat in Iran.

Colonic intussusception in descending colon: An unusual presentation of colon lipoma.

Abstract: Lipomas of the colon are relatively rare benign soft tissue tumors derived from mature adipocytes of mesenchymatic origin. During colonoscopy, surgery or autopsy they are generally discovered incidentally. Most cases are asymptomatic, with a small tumor size, and do not need any special treatment. However, in the cases with larger in size of tumor some symptoms such as anemia, abdominal pain, constipation, diarrhea, bleeding, or intussusception may be presented. We reported a 47-year-old woman with colonic intussusception in the descending colon caused by colonic lipoma and diagnosed after surgical exploration for obstructive colonic mass.

Genetic characterization of Cryptosporidium spp. among patients with gastrointestinal complaints.

Abstract: AIM This study investigated subtypes of Cryptosporidium in patients with gastrointestinal complaints in Tehran, Iran. BACKGROUND Cryptosporidium, an intracellular protozean parasite, is among the major causative agents of gastroenteritis disorders in humans. It also causes water-borne and food-borne outbreaks of diarrheal diseases. PATIENTS AND METHODS A total of 1685 fecal samples were collected from patients with gastrointestinal complaints who had been referred to clinical laboratories Tehran, Iran. The primary diagnosis was established by the detection of oocysts using the modified Ziehl-Neelsen staining method and following that, the positive microscopically samples were selected for sequence analysis of the partial 60 kDa glycoprotein (gp60) gene. RESULTS Out of 1685 collected samples, 7 (0.4 %) were positive for Cryptosporidium oocysts. Sequence analysis of gp60 gene in seven Cryptosporidium isolates revealed that two subtype families were identified, IIa and IId. Five (of 7) isolates belonged to the subtype family IIa and the remaining two isolates belonged to IId. Two sub-types were recognized within the subtype family II,a including IIaA16G2R1 (3/5), IIaA17G1R1 (2/5), while IIdA17G1d was the only subtype within IId subtype family. CONCLUSION The predominance of zoonotic subtype families of C. parvum species (IIa, IId) in this study highlights the importance of zoonotic transmission of cryptosporidiosis in the country.