Publications by authors named "Masoud Reza Sohrabi"

12 Publications

  • Page 1 of 1

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Diabetes Ther 2021 Feb 14. Epub 2021 Feb 14.

Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Introduction: To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM).

Methods: In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg (n = 35), pioglitazone 30 mg (n = 34), or placebo (n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans. Body composition assessment was performed by dual-energy x-ray absorptiometry (DEXA) scans. The primary end point was change from baseline in liver steatosis, using the controlled attenuation parameter (CAP) score.

Results: A borderline significant decrease in CAP score was observed with empagliflozin compared to placebo, mean difference: - 29.6 dB/m (- 39.5 to - 19.6) versus - 16.4 dB/m (- 25.0 to - 7.8), respectively; p = 0.05. Using multivariate analysis, we observed a significant reduction in the placebo-corrected change in liver stiffness measurement (LSM) with empagliflozin compared to pioglitazone: - 0.77 kPa (- 1.45, - 0.09), p  = 0.02, versus 0.01 kPa (95% CI - 0.70, 0.71, p  = 0.98), p for comparison = 0.03. Changes in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), HOMA2-IR, fibrosis-4 index (FIB4 index), NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index (APRI), android/gynecoid ratio (A/G ratio), and skeletal muscle index (SMI) were comparable between the two treatment groups, while significant reductions of the body weight and visceral fat area were observed only in the empagliflozin group (p  < 0.001 and p  = 0.01, respectively) and both were increased in the placebo and pioglitazone groups. There were no serious adverse events in either group.

Conclusion: Treatment for 24 weeks with empagliflozin, in contrast to pioglitazone, was associated with improvement of liver steatosis and fibrosis in patients with NAFLD and T2DM. In addition, body weight and abdominal fat area were decreased in the empagliflozin group.

Trial Registration: Iranian Registry of Clinical Trials (IRCT), IRCT20190122042450N3.
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http://dx.doi.org/10.1007/s13300-021-01011-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882235PMC
February 2021

Erythrocyte membrane fatty acid profile & serum cytokine levels in patients with non-alcoholic fatty liver disease.

Indian J Med Res 2018 04;147(4):352-360

Gastrointestinal & Liver Disease Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background & Objectives: Fatty acids may affect the expression of genes, and this process is influenced by sex hormones. Cytokines are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), so this study was aimed to assess the association of erythrocyte membrane fatty acids with three cytokines and markers of hepatic injury in NAFLD patients and to explore whether these associations were the same in both sexes.

Methods: In this cross-sectional study, 62 consecutive patients (32 men and 30 women) with NAFLD during the study period. Tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), aspartate aminotransferase and alanine aminotransferase were measured in a fasting serum sample, and Fibroscan was conducted for each individual. Gas chromatography was used to measure erythrocyte membrane fatty acids. Univariate and multiple linear regressions were used to analyze data.

Results: In men, IL-6 had a significant (P <0.05) positive association with total ω-3 polyunsaturated fatty acids (PUFAs). In women, TNF-α had a significant positive association with total ω-3 (P <0.05) and ω-6 (P <0.01) PUFAs, IL-6 had a significant (P <0.05) positive association with total monounsaturated fatty acids and MCP-1 had a significant positive association with total trans-fatty acids (P <0.05). No significant associations were observed between erythrocyte membrane fatty acids and liver enzymes or Fibroscan report in both sexes. In this study, women were significantly older than men [51 (42.75-55) vs 35.5 (29-52), P <0.01], so the associations were adjusted for age and other confounders.

Interpretation & Conclusions: Erythrocyte membrane fatty acid profile was not associated with serum liver enzymes or Fibroscan reports in NAFLD patients, but it had significant associations with serum TNF-α, IL-6 and MCP-1 and these associations were probably sex dependent.
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http://dx.doi.org/10.4103/ijmr.IJMR_1065_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057244PMC
April 2018

Hirschsprung Disease Diagnosis: Calretinin Marker Role in Determining the Presence or Absence of Ganglion Cells.

Iran J Pathol 2016 ;11(4):409-415

Gastrointestinal and Liver Diseases Research Center, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

Background: Hirschsprung disease is a complex genetic disorder of the enteric nervous system (ENS), often called congenital aganglionic megacolon and characterized by the absence of enteric neurons along a variable length of the intestine. The definitive diagnosis of Hirschsprung disease relies on histologic and/or histochemical staining of sections from suction rectal biopsies. Calretinin immunohistochemistry (IHC) may be a useful in its diagnosis. This study aimed to proof the usefulness of immunohistochemical staining for calretinin in rule out of Hirschsprung disease.

Methods: Paraffin blocks and slides were retrieved from the pathology archives of Ali Asghar Hospital, Tehran, Iran from 2007 to 2011 with pathology report based on the presence (14 patients) or absence (70 patients) of ganglion cells and transitional zone anatomical region (10 patients). Slides were stained with hematoxylin and eosin method to confirm the initial diagnosis was verification again. After preparing the slides, they were stained by IHC for calretinin. Then, the results were analyzed using SPSS software.

Results: In most patients, IHC for calretinin provided highly compatible results with hematoxylin-eosin findings in diagnosis of Hirschsprung disease. The values of specificity and accuracy between calretinin and standard histology (H&E) compared by the Fisher exact test declared calretinin presented significantly higher specificity and accuracy values than H&E staining ( <0.0001).

Conclusion: Calretinin IHC overcomes most of the difficulties encountered using the histology hematoxylin-eosin. Then, IHC for calretinin is a good ancillary method used by pathologists in diagnosis of Hirschsprung disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563939PMC
January 2016

Household Food Insecurity is Associated with Health-Related Quality of Life in Rural Type 2 Diabetic Patients.

Arch Iran Med 2017 Jun;20(6):350-355

8)Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran. 9)School of Public Health, Zabol University of Medical Sciences, Zabol, Iran.

Background: Health-related quality of life (HRQOL) is associated with household food insecurity (HFI). However, the studies examining the relationship between HFI and HRQOL in patients with type 2 diabetes are scarce. Thus, this study was designed to examine the relationship between HFI and HRQOL in rural type 2 diabetic patients.

Methods: In this cross-sectional study, we included 1847 rural patients with type 2 diabetes in Neyshabur from April to July 2012. HRQOL and HFI were measured with 36-item HRQOL (SF-36) and 6-item version of Household Food Security questionnaires, respectively. HRQOL was divided into eight dimensions and two summary components. We categorized households as high food secure (HFS), low food secure (LFS), and very low food secure (VLFS). Multiple linear regression model was applied to assess the independent effect of food insecurity on HRQOL.

Results: The mean age of participants was 59.65 ± 12.3 years (range: 30-97) with 69.8% women. The overall prevalence of HFI was 46.1%, and the total mean score of HRQOL was 51.11. Multiple linear regression model showed that HFI was significantly associated with the total mean score of HRQOL and its eight dimensions. One-way ANOVA test also showed that HRQOL (in all dimensions) was significantly different between 3 groups of household food security status (HFS, LFS, and VLFS) (P < 0.05).

Conclusions: The results of this study showed that HFI was associated with all dimensions of HRQOL and it is one of the strongest variables, in association with HRQOL among rural patients with type 2 diabetes.
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http://dx.doi.org/0172006/AIM.006DOI Listing
June 2017

Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers

Asian Pac J Cancer Prev 2016 12 1;17(12):5147-5152. Epub 2016 Dec 1.

Department of Virology, Faculty of Medicine,Shahid Beheshti University of Medical Sciences, Tehran, Iran. Email:

Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.
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http://dx.doi.org/10.22034/APJCP.2016.17.12.5147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454650PMC
December 2016

Association between Nicotinamide Phosphoribosyltransferase and de novo Lipogenesis in Nonalcoholic Fatty Liver Disease.

Med Princ Pract 2017 9;26(3):251-257. Epub 2017 Jan 9.

Gastrointestinal and Liver Disease Research Center (GILDRC), Iran University of Medical Sciences, Tehran, Iran.

Objective: This study explored the association between serum nicotinamide phosphoribosyltransferase (NAMPT) and hepatic de novo lipogenesis (DNL) in nonalcoholic fatty liver disease (NAFLD) and determined whether or not this association is sex dependent.

Subjects And Methods: In this cross-sectional study, 62 consecutive patients (32 males, 30 females) with NAFLD were recruited. Serum NAMPT (by ELISA), palmitic acid, and the DNL index of erythrocyte membranes as markers of hepatic DNL (by gas chromatography) were analyzed. The controlled attenuation parameter (CAP) and body impedance analyzer were used to assess hepatic and body fat, respectively. Univariate and multiple linear regressions (to adjust for confounders) were used to analyze the association of serum NAMPT with palmitic acid, DNL index, CAP, and body fat.

Results: The respective values of serum NAMPT (2.44 ± 1.03 vs. 2.45 ± 1.13 ng/mL, p = 0.98), DNL index (3.11 [2.60-3.71] vs. 3.05 [2.40-3.59], p = 0.90), and palmitic acid (20.55% [15.34-24.04] vs. 22.64% [21.15-25.95], p = 0.07) were not significantly different between men and women, but those of CAP (326 [300-340] vs. 300 [261.25-329], p = 0.002) and body fat (37.71 ± 3.80 vs. 26.60 ± 5.70, p < 0.001) were significantly higher in women. In women, serum NAMPT had a significant negative association with the DNL index (β = -0.56, p = 0.01). The DNL index also had a significant negative association with body fat (β = -0.46, p = 0.02). In men, the only significant association was the positive association between serum NAMPT and CAP (β = 0.35, p = 0.035).

Conclusion: Higher serum NAMPT in women was associated with a lower hepatic DNL index, while in men it was associated with higher hepatic fat and had no association with the DNL index. Therefore, the serum NAMPT level interpretation for NAFLD prognosis is probably sex dependent.
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http://dx.doi.org/10.1159/000455862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588391PMC
March 2018

Mutation Analysis of KRAS and BRAF Genes in Metastatic Colorectal Cancer: a First Large Scale Study from Iran.

Asian Pac J Cancer Prev 2016 ;17(2):603-8

Gastrointestinal and Liver Diseases Research Center, Firoozgar Hospital, Iran University Of Medical Sciences, Tehran, Iran E-mail :

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features.

Materials And Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these.

Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics.

Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.
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http://dx.doi.org/10.7314/apjcp.2016.17.2.603DOI Listing
January 2017

Prevalence of Non-Alcoholic Fatty Liver Disease and Its Predictors in North of Iran.

Iran J Public Health 2014 Sep;43(9):1275-83

1. Gastrointestinal and Liver Disease Research Center (GILDRC), Iran University of Medical Sciences , Tehran, Iran.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the aspects of metabolic syndrome (MetS). Due to the increase of MetS in Iran, this study was conducted to determine the prevalence of NAFLD, its potential predictors and their sex distribution in north of Iran, Amol.

Methods: In 2008 this population based cross-sectional study included 5023 adult individuals who were randomly selected from Amol healthcare centers. Blood analysis and hepatic sonography was performed for each individual and Clinical histories were reviewed. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III. Chi-square test, univariate and multivariate logistic regression were used to analyze data.

Results: The prevalence of NAFLD and metabolic syndrome was 43.8% and 29.6% respectively. Both NAFLD and metabolic syndrome were significantly more prevalent in women. There was a stronger association between these two factors in women which may indicate MetS has a much more potency to result in NAFLD in women. The strongest predictors of NAFLD in men were waist circumference>102 cm, serum ALT ≥40 (U/L) and the age group of 40-60 years. The strongest predictors of NAFLD in women were waist circumference>88 cm, the age groups of 40-60 and >60 years.

Conclusions: The observed prevalence is alarming because almost 7out of 10 subjects with MetS had NAFLD. As high waist circumference was an important predictor of NAFLD in both sexes, health care policies to reduce the incidence of obesity in the country will have an important impact on the occurrence of NAFLD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500430PMC
September 2014

Evaluation of HER-2/neu overexpression in gastric carcinoma using a tissue microarray.

Asian Pac J Cancer Prev 2014 ;15(18):7597-602

Department of Pathology, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran E-mail

Background: Amplification and overexpression of human epidermal growth factor receptor 2 (HER2 / neu) oncogene has considerable prognostic value in breast and gastric cancers. This study aimed to evaluate the frequency, overexpression pattern, clinical significance, and concordance between the results for protein expression and gene amplification of HER-2/neu in gastric and gastro-esophageal junction carcinomas.

Materials And Methods: In this study, 101 gastric tissue samples which were included in tissue microarray were immunohistochemically examined for overexpression of HER2/neu. Chromogenic in situ hybridization (CISH) was used for HER-2/neu amplification. The correlation of HER2/neu amplification with clinicopathological parameters was also assessed. In addition, concordance between CISH and IHC was detected.

Results: This study demonstrated a significant difference in the overexpression of HER2/neu in gastric tumors. The overexpression of HER2/neu was significantly higher in intestinal type, poorly differentiated grade, large size (5 cm≤) and positive nodal involvement tumors (p-value=0.041, 0.015, 0.038 and 0.071, respectively). Also, amplification of HER2/neu according to CISH test, had a significant positive correlation with tumor size and tumor type (p-value=0.018 and 0.058, respectively).Concordance between CISH and IHC was 76.9% in 101 evaluable samples.

Conclusions: IHC/CISH differences were attributed to basolateral membranous immunoreactivity of glandular cells resulting in incomplete membranous reactivity and/or a higher rate of tumor heterogeneity in gastric cancers compared to breast cancers. Therefore, this can be a potential marker for targeted therapy of malignant gastric tumors.
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http://dx.doi.org/10.7314/apjcp.2014.15.18.7597DOI Listing
June 2015

Thyroid dysfunction and choleduocholithiasis.

Middle East J Dig Dis 2013 Jul;5(3):141-5

Gastrointestinal and Liver Disease Research Center (GILDRC), Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

Background: Disturbances in lipid metabolism which occur during hypothyroidism leadto the formation of gallstones. This study aims to evaluate the thyroid functionpattern in patients with common bile duct (CBD) stones.

Methods: This case-control study recruited 151 patients with preliminary diagnosesof CBD stone who underwent ERCP (cases). The control group comprisedhealthy people who met the study criteria in the same hospital. The controlgroup underwent ultrasonography to exclude any asymptomatic bile duct lithiasis.A questionnaire that included demographic and anthropometrics datawere completed by an assigned physician. Morning blood samples that followed12 hours of fasting were taken from all participants for measurements ofserum total thyroxin (T4), serum thyroid stimulating hormone (TSH), fastingblood sugar (FBS), triglycerides (TG), total cholesterol, low density lipoprotein(LDL) and high density lipoprotein (HDL).

Results: The mean TSH in patients (2.59 ± 4.86mg/dl) was higher than the controlgroup (2.53± 4.13 9mg/dl). In subclinical hypothyroidism, serum TSH levelshigher than 5 MU/L were found in 30.6% of cases compared with 22.5% ofcontrols [OR: 1.53; 95 % confidence interval (95% CI): 0.968-2.438). Hypothyroidismwas detected in 10.8% of the control group and in 11.3% of cases(OR: 1.87; 95% CI: 0.578-2.043). The mean total cholesterol levels in caseswas higher than the control group (p=0.61).The levels of TG (p=0.05), HDL(73.35 vs. 46.41; p<0.01) and LDL (64.81.88 vs. 111.04; p<0.01) was statisticallysignificant between both groups.

Conclusion: There is an association between thyroid disorders and the presence of bileduct stones. Thyroid testing in patients with gallstone and bile duct stones isrecommended because hypothyroidism may be a predisposing factor for stonepassage from the gallbladder.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990180PMC
July 2013

Probucol in the treatment of non-alcoholic steatohepatitis: a double-blind randomized controlled study.

J Hepatol 2003 Apr;38(4):414-8

Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Shomali Avenue, Tehran, Iran.

Background/aims: A final step in the pathology of non-alcoholic steatohepatitis (NASH) is oxidative damage to hepatocytes. Probucol is a lipid-lowering agent with strong antioxidant properties. We designed a double-blind randomized controlled study to evaluate the effects of probucol in NASH.

Methods: Thirty cases of biopsy-proven NASH were included. Subjects were randomly allocated to either the treatment group or to the control group by a 2:1 ratio. The treatment group was given 500 mg of probucol daily for 6 months, and the control group, an identically appearing placebo.

Results: Twenty-seven cases completed the study. The mean aspartate transaminase (AST) and alanine transaminase (ALT) levels changed from 81.9 to 36.2 and 102.2 to 44.7 in the treatment group and from 57.6 to 49.6 and 96.8 to 96.2 in the control group, respectively. The decrease in ALT level in the treatment group as compared to the control group was significant at the P<0.005 level (95% confidence interval: 20.2-93.7 IU). Both AST and ALT levels dropped to normal in nine cases of the treatment group (50%) but none of the control group (P=0.01).

Conclusions: Probucol appears to be significantly effective in decreasing the ALT levels in patients with NASH.
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http://dx.doi.org/10.1016/s0168-8278(02)00441-5DOI Listing
April 2003

Probucol in the treatment of nonalcoholic steatohepatitis: an open-labeled study.

J Clin Gastroenterol 2003 Mar;36(3):266-8

Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Goals: To evaluate the effects of probucol, an agent with strong antioxidant properties, in reversing biochemical changes in nonalcoholic steatohepatitis (NASH).

Background: There is currently no well-established medical treatment of NASH. It is believed that oxidative stress plays a major role in hepatic damage in these patients.

Study: Cases of biopsy-proven NASH referring to a referral center in Tehran during a 12-month period were included in the study. Viral, autoimmune and other hepatic diseases were excluded. Alcohol ingestion was excluded by repeated questioning of the patient and at least two family members. Patients were given 500mg of probucol daily for 6 months. Serum levels of liver enzymes, the serum lipid profile, and weight was recorded monthly.

Results: A total of 17 patients completed the study. The mean age was 37.2 years, 13 patients were male and 4 female. The mean pretreatment value of ALT and AST was 93.5 and 80.4 U/L, and the mean posttreatment value was 41.8 and 35.9 U/L respectively ( = 0.001 and 0.006).

Conclusion: Probucol, even in the low dose of 500 mg/d, appears to be significantly effective in decreasing the ALT and AST levels in patients with NASH.
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http://dx.doi.org/10.1097/00004836-200303000-00015DOI Listing
March 2003