A population-based prospective study on obesity-related non-communicable diseases in northern Iran: rationale, study design, and baseline analysis.

Background: Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population. Method: We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively. Results: We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years. Conclusion: The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran.

Diagnostic Accuracy of Vibration Controlled Transient Elastography as Non-invasive Assessment of Liver Fibrosis in Patients with Non-alcoholic Fatty Liver Disease.

Background: Liver biopsy remain as the gold standard for diagnosing hepatic fibrosis; however, it has some limitations, such as life-threatening complications, low acceptance by the patients, and variations in the related sample. Therefore, there is a need for the development of non-invasive investigations for diagnosing hepatic fibrosis. Vibration-controlled transient elastography (VCTE) is one of these non-invasive methods. Methods: This study included 73 patients suffering from non-alcoholic fatty liver disease (NAFLD) who were older than 18 years. The patients underwent VCTE at the Baqiatallah and Firoozgar hospitals. Then, they underwent a liver biopsy by an experienced radiologist in the same hospital. A receiver operating characteristic (ROC) curve of different fibrosis stages was used to evaluate the VCTE verification. Results: VCTE could detect any fibrosis levels (stage 1 and higher) with an area under the ROC curve (AUROC) of 0.381. Moreover, it detected stage 2-4 fibrosis with an AUROC of 0.400, stage 3-4 fibrosis with an AUROC of 0.687, and stage 4 fibrosis with an AUROC of 0.984. Conclusion: The VCTE has high clinical validity in diagnosing the advanced stages of fibrosis (stages 3, 4) and can be a suitable alternative to the invasive method of liver biopsy with high reliability.

Candidate Molecular Biomarkers for the Non- Invasive Detection of Colorectal Cancer using Gene Expression Profiling.

BACKGROUND & OBJECTIVE: olorectal Cancer (CRC) is the third most common cancer after prostate (breast in women) and lung cancer; it is also the third cause of cancer deaths reported in both men and women in 2020. Currently, the most commonly used diagnostic tools for CRC are colonoscopy, serological methods, and other imaging techniques. Despite the benefits and abilities of these methods, each of them has disadvantages that reduce its functionality and acceptance. The aim of this study was identifying specific and non-invasive genetic biomarkers to diagnose colorectal cancer. METHODS: In this study, changes in the expression of HLTF and SEPT9 genes were evaluated by Real Time PCR in blood and tissue samples of CRC patients. A total of 100 samples (50 Blood and 50 Tissue samples) were evaluated with a definite diagnosis of CRC in Firoozgar Hspital, Tehran, Iran, in 2018. The QPCR method was used to compare the expression of candidate genes between the patients group and control group in both samples. Sensitivity and specificity of the test were examined using ROC curve analysis. RESULTS: The results showed a significant down-regulation in the expression of both selected genes in tissue and peripheral blood in the various stages of the CRC. The sensitivity and specifity of both genes was about 80%. CONCLUSION: The findings showed that the two candidate genes can be suggested as specific biomarkers for diagnosis of CRC using the peripheral blood as a non-invasive method. For a definite conclusion, more research is needed.

Relationship between dietary macronutrient composition and non-alcoholic fatty liver disease in lean and non-lean populations: a cross-sectional study.

OBJECTIVE: The current study aimed to customize dietary changes for lean patients with non-alcoholic fatty liver disease (NAFLD). DESIGN: The current study was done with a population-based cross-sectional design. The FFQ was used to analyse dietary macronutrient intake and ultrasonography results for NAFLD diagnosis. The study subjects were divided into the lean and non-lean groups based on their BMI (< 25 and ≥ 25). Multivariable logistic regression was used to evaluate the relationship between dietary macronutrients and NAFLD. Substitution analyses were also performed. SETTING: Amol and its suburban areas in Iran. PARTICIPANTS: Adults in the age range of 18 to < 65 with full relevant data. RESULTS: Among the total study subjects (2308), 46·7 % had fatty liver. The substitution of polysaccharides for animal protein and SFA in the lean group resulted in a significant NAFLD reduction, whereas the substitution of SFA for all types of macronutrients, except for n-6 and mono-disaccharides, led to a significant increase in NAFLD (P < 0·05). In non-lean participants, the substitution of MUFA for mono-disaccharides resulted in a significant reduction of NAFLD (P < 0·05). In this group, the substitution of SFA and mono-disaccharides for MUFA, and n-6 for all macronutrients, except vegetable protein and SFA, were significantly related to an increase in NAFLD (P < 0·05). CONCLUSIONS: Lower lean NAFLD is correlated with increasing polysaccharides in exchange for SFA and animal protein intake, whereas lower non-lean NAFLD is correlated with increasing MUFA in exchange for mono-disaccharides and reducing n-6 and SFA.

Role of microbiota-derived short-chain fatty acids in cancer development and prevention.

Following cancer, cells in a particular tissue can no longer respond to the factors involved in controlling cell survival, differentiation, proliferation, and death. In recent years, it has been indicated that alterations in the gut microbiota components, intestinal epithelium, and host immune system are associated with cancer incidence. Also, it has been demonstrated that the short-chain fatty acids (SCFAs) generated by gut microbiota are vitally crucial in cell homeostasis as they contribute to the modulation of histone deacetylases (HDACs), resulting effected cell attachment, immune cell immigration, cytokine production, chemotaxis, and the programmed cell death. Therefore, the manipulation of SCFA levels in the intestinal tract by alterations in the microbiota structure can be potentially taken into consideration for cancer treatment/prevention. In the current study, we will explain the most recent findings on the detrimental or protective roles of SFCA (particularly butyrate, propionate, and acetate) in several cancers, including bladder, colon, breast, stomach, liver, lung, pancreas, and prostate cancers.

Bizhan Aarabi and Knowledge Development in Neurotrauma.

Neurotrauma (NT) is one of the common causes of mortality and morbidity. Investigating the role of people who had an impact on the development of knowledge of NT is reasonable. Our aim is to investigate the role of Bizhan Aarabi, professor of Neurosurgery, on the knowledge development in NT. Accordingly, we searched the Scopus database for Bizhan Aarabi on August 8, 2020 and selected papers with at least 10 citations, investigating his impact on NT and details of his publications. He has published 168 papers including original articles, reviews, conference papers, letters, and editorials according to the Scopus databases. There are 112 papers with 10 or more citations. Thirty-eight out of 112 papers (33.9%) were in the first and the highest rank journal: 29 in Neurosurgery and 9 in the Journal of Neurotrauma. Twenty-four papers have the level of evidence (LOE) of "1". Bizhan Arabi developed knowledge in NT especially in the cervical spine/spinal cord trauma and brain injury and his publications are references for spine/neurosurgeons.

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.

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.

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

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.

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

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.

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

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 (ß = -0.56, p = 0.01). The DNL index also had a significant negative association with body fat (ß = -0.46, p = 0.02). In men, the only significant association was the positive association between serum NAMPT and CAP (ß = 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.

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

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.

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

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.

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

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 (P <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.

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

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.

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

Thyroid dysfunction and choleduocholithiasis.

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.

New 1,2,4-triazole-based azo-azomethine dyes. Part II: synthesis, characterization, electrochemical properties and computational studies.

A new series of monoiminated 1,2,4-triazole-based azo-azomethine dyes have been synthesized via condensation reaction of 4-amino-3-methyl-5-mercapto-1,2,4-triazole with various substituted azo-coupled salicylaldehyde. The dyes have been characterized by using FT-IR, UV-Vis and (1)H NMR spectroscopic methods as well as elemental analysis. The electrochemical behavior of the dyes has been investigated by cyclic voltammetry in DMSO at five different scan rates. Solvatochromic behavior of the dyes has been also investigated in four organic solvents with different polarities. Furthermore, the (1)H chemical shielding of the dyes were studied by the gauge independent atomic orbital (GIAO) method at the level of density functional theory (DFT).

Liver histology changes in nonalcoholic steatohepatitis after one year of treatment with probucol.

BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is effective in normalizing liver enzymes in patients with nonalcoholic steatohepatitis (NASH). We studied changes in the liver histology of patients with NASH after use of probucol for one year. METHODS: Ten patients with biopsy-proven NASH were included. Subjects were given 500 mg probucol daily. Liver biopsies were performed before treatment and after one year. RESULTS: Eight patients completed treatment. The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26, respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed. CONCLUSION: Probucol is effective in normalizing aminotransferase levels in patients with NASH. It also significantly reduces the histology grade of steatohepatitis after one year of treatment.

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

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.

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

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.