Gastroenterology and Hepatology from Bed to Bench

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An inflammatory bowel disease (IBD) is most common in highly industrialized Western countries but uncommon in less developed areas of the world where helminths are frequent. The hygiene hypothesis proposes that the recent increase in allergic and autoimmune diseases is due to modern highly hygienic life styles and medical conditions. Loss of routine exposure to parasitic helminths, as a result of increasing lifestyle-associated factors, may be one factor leading to the increased disease prevalence.

In animal models and clinical trials of IBD, gastrointestinal nematodes colonization suppresses intestinal inflammation through multiple mechanisms including induction of innate and adaptive regulatory circuits. Studies using helminths like Trichuris suis or Necator americanus showed that these helminths are safe and may be effective therapeutic approaches for the control of IBD and other immune diseases. The aim of present review was to exploring the therapeutic use of helminths for the control of IBD.

The physical interaction of proteins which lead to compiling them into large densely connected networks is a noticeable subject to investigation. Protein interaction networks are useful because of making basic scientific abstraction and improving biological and biomedical applications. Based on principle roles of proteins in biological function, their interactions determine molecular and cellular mechanisms, which control healthy and diseased states in organisms. Therefore, such networks facilitate the understanding of pathogenic (and physiologic) mechanisms that trigger the onset and progression of diseases. Consequently, this knowledge can be translated into effective diagnostic and therapeutic strategies. Furthermore, the results of several studies have proved that the structure and dynamics of protein networks are disturbed in complex diseases such as cancer and autoimmune disorders. Based on such relationship, a novel paradigm is suggested in order to confirm that the protein interaction networks can be the target of therapy for treatment of complex multi-genic diseases rather than individual molecules with disrespect the network.

Aim: The present study was designed to assess the impact of neo-adjuvant chemoradiotherapy on the possibility of utilizing sphincter preserving techniques in rectal cancer surgery.

Background: For both patients and surgeons anal sphincter preserving surgery serves as the ideal procedure to treat rectal cancer.

Patients and methods: Patients with rectal cancer who were admitted to Shohadaye Tajrish hospital between 2001 and 2011 and underwent sphincter preserving or non-preserving surgery were identified. They were divided into those who had received neo-adjuvant chemo-radiotherapy prior to surgery and those who didn't, and the type of surgical procedure they underwent was compared between the two arms. Data regarding tumor pathology, tumor size and distance from anal verge before and after neo-adjuvant therapy, together with the duration of chemo-radiotherapy were also assessed.

Results: 103 patients with documented rectal cancer were included in our analysis. Among 47 patients who had not received neo-adjuvant therapy, 26 (55%) underwent APR while 15(32%) and 6(13%) patients were treated with LAR and VLAR respectively. Of the 56 patients who had gone through chemo-radiotherapy prior to surgery, 30 (53%) underwent APR while 14 (25%) and 10 (18%) patients were treated with LAR and VLAR respectively. 2 patients had unresectable tumor. Tumor staging before and after neo-adjuvant therapy showed a statistically significant difference (p=0.0001).

Conclusion: Neo-adjuvant chemo-radiotherpy can decrease tumor size, increase the distance between the tumor and anal verge, and downgrade the staging. However, it does not necessarily increase the possibility of performing sphincter preserving surgery on patients suffering from low-lying tumors.

Aim: The purpose of this study was to find the isolation rate of enteropathogenic Escherichia coli (EPEC) from lettuce samples collected in Tehran.

Background: During the last decade, the prevalence of infectious diarrheal diseases due to consumption of contaminated food especially raw vegetable has been increasingly reported. Enteropathogenic Escherichia coli strains are an important group of diarrheagenic E. coli that can cause infant diarrhea especially in the developing world.

Material and Methods: One hundred lettuce samples collected in Tehran were transported to the laboratory, homogenized by a stomacher in EC broth containing cefixime, and cultured on MacConkey agar plates. Bacterial DNA was extracted by boiling method and PCR was performed using three pairs of primers targeting stx₁, stx₂ and eaeA genes.

Results: Screening of 100 lettuce samples by PCR showed four samples were positive for the presence of EPEC.

Conclusion: This study suggests contamination of the lettuce by the EPEC and its possible role as the source of infection in this region.

Aim: We evaluated the capability of “microRNA sponges” in sequestering and inhibiting the over-expressed miR-221 in HCC cell lines.

Background: Advanced hepatocellular carcinoma (HCC) is a serious public health problem, with no effective cure at present. It has been demonstrated that the deregulation of microRNAs expression contributes to tumorigenesis. In HCC, miR-221 was shown to be up-regulated in more than 70% of the cases and was associated with higher tumor stage, metastasis and a shorter time to recurrence after surgery, suggesting an important pathogenic role. A tumor promoting function of miR-221 was proved in a transgenic mouse model, which was predisposed to the development of liver cancers. These findings suggested that miR-221 could represent a potential target for anti-tumor approaches.

Material and Methods: Novel adeno and adeno-associated viral vectors (AAVs) were developed: they were genetically modified to drive the expression of multiple binding sites for miR-221, the “miR-221 sponge”, which was designed to sequester miR-221 cellular molecules.

Results: Analysis of viral vectors activity in HCC cells revealed their capability to reduce miR-221 endogenous levels, which was accompanied by the increase in CDKN1B/p27 protein, a known target of miR-221. An increase in apoptosis was also measured in Hep3B cells after infection with any of the two viral vectors in comparison with control vectors, with stronger effects induced by adenovirus compared to AAV vectors.

Conclusion: The depletion of oncogenic microRNAs represents a potential anti-cancer approach that needs to be tested for safety and efficacy. Here, we describe the development of novel “miR-221 sponge” vectors, which can reduce miR-221 activity in vitro and may be used for in vivo delivery.

Aim: This study aimed to evaluate the effect of NAFLD on CIMT as a risk factor for atherosclerosis.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide due to rise of obesity and diabetes mellitus (DM) prevalence. Non-invasive assessment of carotid intima-media thickness (CIMT) by high-resolution carotid B-mode ultrasonography is widely used for determining the atherosclerosis.

Patients and methods: In this case-control setting, 151 subjects were categorized in three groups: group I including 49 patients with NAFLD and DM; group II including 50 non-diabetic NAFLD patients; and the control including 52 normal subjects as group III. The right and left CIMTs and its maximum reading (CIMT_max) were measured by a skilled sonographist blind to the groups. The sonographic grading of the NAFLD was determined in group I and II.

Results: Median CIMT_max was significantly higher in group I comparing with group II and control group (p<0.001). This difference between group I and group II was not significant after adjusting for age and history of hypertension and hyperlipidemia (p=0.089). After controlling the confounders, there was statistical significant between group I and group II with the control group (p<0.05). There was no significant difference in median maximal thickness of intima-media in the carotid of group I compare to group II in patients with and without elevated liver enzymes (in both groups, 0.6 mm, p= 0.402).

Conclusion: Based on our findings, there is a significant association between the presence of NAFLD and atherosclerosis. This association was independent to the DM presence. The grade of NAFLD and elevated liver function tests had no effect on severity of atherosclerosis.

Aim: This study was conducted to investigate a possible association between H. pylori infection and CSR.

Background: Helicobacter pylori infection is one of the most common infections worldwide. Central Serous Chorioretinopathy (CSR) is a serious macular detachment that usually affects young people. The etiopathogenesis of the disease is still not completely understood.

Patients and methods: A prospective study was performed and we evaluated a total of 35 CSR patients and control group of138 patients who referred to gastroenterology research center of Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Central serous chorioretinopathy was diagnosed on the basis of findings in ophthalmic examinations and confirmed by fluoresce in angiogram. All patients underwent a 13C-urea breath test (UBT) to detect H. pylori infection. Patients were defined as H. pylori infected, if breath test was positive.

Results: The mean duration of symptoms before diagnosis was8.3± 2.5 days. Overall, no statistically significant difference was found between left and right eyes, bilateral CSR was observed in 5 patients (14.2%).The incidence of H. pylori infection was 85.7% in CSR patients and 55.1% in control subjects (p=0.001). Odd’s ratio was 4.895.

Conclusion: These results indicate that the prevalence of H. pylori infection is significantly higher in patients with CSR than in controls. No effect of age or sex was seen on H.pylori test results. Further multiple centers, randomized, case control trials are necessary to confirm the potential contributory role of the H. pylori infection in the pathogenesis of CSR as a possible association between infectious agents and endothelial dysfunction.

Mirizzi’s syndrome is a rare complication of gallstone disease , that gallbladder lumen can lie alongside the common hepatic duct, resulting in inflamation and resultan bile duct stricture . most cases are not indentified preoperatively. variations of the cystic duct and its point of union with the common hepatic duct are surgically important . Here, we present an unusual case of type I Mirizzi’s syndrome with an un common anomalous cystic duct , that long cystic duct joins common hepatic duct behind the duodenum . Also, there is a high bilirubin level due to gallstone and bile duct stone.

A 44-year-old man with upper abdominal pain, diarrhea and 25 kg weight loss since 3 months ago was admitted. He had a history of dyspepsia and peptic ulcer disease 4 months before admission.

Gastroduodenal endoscopy and upper gastrointestinal series with barium study were done. Biopsies and CT-scan ruled out malignancies. Endoscopy and radiology studies revealed a duodenocolic fistula. He underwent right hemicolectomy, fistula en bloc excision, and distal gastrectomy surgery with gastrojejunostomy and ileocolic anastomosis. Radiologic modalities are necessary before surgery. Surgery is the only curative treatment in benign cases and reconstruction method is dependent on patient’s situation.