Simultaneous Underexpression of let-7a-5p and let-7f-5p microRNAs in Plasma and Stool Samples from Early Stage Colorectal Carcinoma.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer death worldwide. Early detection of CRC can improve patient survival rates; thus, the identification of noninvasive diagnostic markers is urgently needed. MicroRNAs (miRNAs) have extensive potential to diagnose several diseases, including cancer. In this study, we compared the expression pattern of miRNAs from plasma and stool samples of patients with early stages of CRC (I, II) with that of healthy subjects. We performed miRNA profiling using microarrays on plasma and stool samples of eight patients with CRC and four healthy subjects. Seven miRNAs were found to be underexpressed in both plasma and stool samples of patients with CRC versus healthy subjects. Then, we aimed to verify two out of these seven differentially expressed miRNAs (let-7a-5p and let-7f-5p) by quantitative reverse transcriptase polymerase chain reaction on a larger set of plasma and stool samples of 51 patients with CRC and 26 healthy subjects. We confirmed the results of microarray analysis since their expression was significantly lower in stool and plasma samples of patients with CRC. Moreover, receiver operating characteristic curve analysis demonstrated that fecal let-7f expression levels have significant sensitivity and specificity to distinguish between patients with CRC and healthy subjects. In conclusion, if the results are confirmed in larger series of patients, underexpressed let-7a-5p and let-7f-5p miRNAs in both plasma and stool samples of patients with CRC may serve potentially as noninvasive molecular biomarkers for the early detection of CRC.

Diagnostic value of fecal calprotectin in patient with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by recurrent episodes of inflammation limited to the mucosal layer of the colon. Calprotectin is a zinc and calcium binding protein derived from neutrophils and monocytes. It is easily detectable in tissue samples, body fluids, and stools, which makes it a potentially valuable marker of inflammation. The aim of the current study is to evaluate the value of fecal calprotectin (FC) as a marker of disease activity in patients with UC. METHODS: Seventy three eligible subjects underwent ileocolonoscopy and multiple biopsies were obtained from different parts of the colon and terminal ileum. All patients underwent blood and stool sampling as well as an interview to assess the disease severity utilizing ulcerative colitis activity index (UCAI), subjectively. The diagnostic value of the FC in comparison with Mayo disease activity index as the gold standard technique, was then evaluated. RESULTS: Mean FC level increased linearly according to Mayo disease activity index (r=0.44, p<0.001) and was significantly different between levels of Mayo disease activity index (p=0.003). In multivariate analysis, Mayo disease activity index, positive CRP and ESR were associated with FC level. FC level > 21.4 ng/ml was able to discriminate between active and inactive phases of UC according to Mayo disease activity index>2 with 72.3% sensitivity and 73.1% specificity. The combination of FC > 21.4 ng/ml and UCAI score of 7 had a 46.8% sensitivity and 88% specificity to diagnose Mayo disease activity index >2. Furthermore, FC level <21.4 ng/ml in combination with UCAI score of <3 showed a highly considerable specificity of 98% to discriminate the remission phase of UC (Mayo disease activity index <2), although with a low sensitivity (31%). CONCLUSION: FC appears to be a non-invasive biomarker with moderate accuracy to discriminate the active phase of inflammatory bowel disease (IBD). The value of FC especially in combination with UCAI is highly considerable to rule out the Mayo disease activity index >2.

Incarceration is a major risk factor for blood-borne infection among intravenous drug users: Incarceration and blood borne infection among intravenous drug users.

BACKGROUND: There is a strong association between hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection which are mainly transmitted by contamination with blood via intravenous drug abuse (IVDU) or sexual contact. OBJECTIVES: To determine the prevalence of these infections and the risk factors associated with them among prisoner and non-prisoner IVDUs in Tehran, Iran. PATIENTS AND METHODS: This cross-sectional study was performed in two jails and three drug rehabilitation centers between 2001 and 2002 in Tehran. HBsAg and HBcAb were checked using highly specific third generation enzyme immunoassays (DIA.PRO, Italy, specificity >99%, and Radim, Italy, specificity 99.7%, respectively). HCVAb was detected using ELISA (DIA.PRO, Italy) with both sensitivity and specificity >98%. HIVAb test (DRG Diagnostics kit, Germany) was performed for 459 of the 468 IDU subjects. RESULTS: 392 prisoners and 135 individual attending drug rehabilitation centers were approached. Of the 518 subjects studied, 464 (89.5%) were male, 386 (74.5%) were prisoners and 132 (25.5%) were non-prisoners. In this study, HBsAg, HCVAb and HIVAb were positive in 19 (3.7%), 359 (69.5%) and 70 (15.5%) of subjects, respectively. These tests were positive in 17 (4.5%), 311 (80.5%) and 63 (17%) among prisoners and 2 (1.5%), 48 (36.5%) and 7 (7.8%) in non-prisoners, respectively. Multiple logistic regression analysis revealed that independent factors related to co-infection of HCV and HIV infection were imprisonment (p<0.001. OR: 7.5) and using common syringe (p=0.03, OR: 4.5). CONCLUSIONS: Our findings strongly suggest that drug injection inside prison carries is a risk for HIV infection and that HIV infection among IDUs is likely to be bridged to the broader population through sexual contact without using effective prevention programs.

Screening of the adult population in Iran for coeliac disease: comparison of the tissue-transglutaminase antibody and anti-endomysial antibody tests.

BACKGROUND AND AIMS: Population-based studies for the prevalence of coeliac disease (CD) in west-Asian countries are scarce. We aimed to determine the prevalence of gluten-sensitive enteropathy (GSE) in the general population of northern and southern Iran, and evaluate the sensitivity and specificity of the anti-endomysial antibody (EMA) immunofluorescent test and the enzyme-linked immunosorbent assay-based test for determination of the IgA anti-tissue transglutaminase antibody (tTG-Ab) using the human recombinant transglutaminase antigen for the detection of CD in screening the asymptomatic adult population. MATERIAL AND METHODS: Using a stratified random sampling method we enrolled a total of 2799 individuals (1438 from Sari and 1361 from Kerman). The mean age was 33.7 years (range 18-66), with 1398 men. IgA anti-tissue transglutaminase (tTG) and IgA anti-EMA were determined in the serum of all subjects. Those participants with a positive serology for any of the two tests underwent small intestinal biopsy, and were classified according to revised Marsh criteria histologically. A diagnosis of GSE was based on positive serology and a compatible histopathological finding. The maximum likelihood latent class model was used to estimate the sensitivity and specificity of the two tests. RESULTS: Twenty-nine cases showed positive IgA tTG-Ab (15 men and 14 women, mean age 35.4 years, range 18-59), whereas only five were simultaneously positive for EMA. Except for two subjects with normal small bowel histology (Marsh 0), all other subjects were found to have biopsy findings compatible with GSE: 18 Marsh I, five Marsh II, three Marsh IIIa and one Marsh IIIc lesions. he prevalence of GSE was 0.96% or 1:104. The sensitivity and specificity of the human-recombinant IgA tTG-Ab assay were 100 and 99%, respectively, whereas the results for IgA EMA were 19 and 100%, respectively. The IgA EMA was positive in cases with advanced mucosal lesions of the small bowel. The mean serum value of IgA tTG-Ab was higher in patients with severe enteropathy compared with those showing slight mucosal changes (P<0.05). CONCLUSION: The minimum prevalence of gluten sensitivity among the general population of northern and southern Iran is 1:104. The best screening test for the detection of GSE in the general population is IgA tTG-Ab.

Hereditary risk factors for the development of gastric cancer in younger patients.

BACKGROUND: It is believed that the development of gastric cancer (GC) before the age of 50 has a hereditary basis. Blood group A and history of gastric cancer in first-degree relatives have been shown to be risk factors for GC. METHODS: In this case-control study, we enrolled patients with GC who were diagnosed before the age of 50. Patients who were diagnosed as having GC were selected. A total of 534 cases were found; of these, 44 diagnosed before the age of 50 were included in the case group. For the control group, 22 males and 22 females were randomly selected from the remaining subjects, who had diagnoses of GC after the age of 50. All the surviving patients and family members of the dead patients were interviewed about the history of cancer in the family and the age at which other family members developed cancer. The blood group of each subject was also obtained. RESULTS: forty-four cases under 50 years old (mean age: 36.2 years) and forty-four controls (mean age: 67.1 years) were enrolled in the study. At the time of the study, 59.1% of the study group and 50% of the control group were alive (P value = NS). In the study group, 68.1%, 13.6%, 13.6% and 4.5% had blood groups O, A, B and AB, respectively. In the control group the corresponding figures were 27.7%, 63.6%, 6.8% and 4.5%. First or second-degree relatives with cancer, including gastric (the most frequent), breast, lung, gynecological and hematological malignancies, were noted in 54.5% of the cases and 11.4% of the controls (p < 0.01). Family histories of cancer were accepted as valid provided that they were based on valid medical documents. CONCLUSIONS: It seems that the development of GC before the age of 50 is likely to be accompanied by familial susceptibility. Interestingly, our study showed a significant correlation between blood group O and the development of gastric cancer under the age of 50.