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Diabetes mellitus and hypertension are the two main etiologies of chronic kidney disease (CKD). However, CKD subjects of unknown origin (CKDu) have been recognized recently. One of the proposed causes is pesticide use in farmers. On the other hand, house use of pesticides has never been investigated in developing countries. In this study, we aimed to investigate the association between house use of pesticide and their exposure time with CKDu. This study is part of the population-based cohort of Prospective Epidemiological Research Studies in Iran. We used the baseline data of the Zahedan Adult Cohort Study. We dropped all subjects with diabetes mellitus and/ or hypertension, egfr 60-89 ml/min/1.73 m2, and unavailable creatinine measurement. Subjects with egfr of less than 60 ml/min/1.73 m2through MDRD equations were defined as CKDu and compared with subjects with egfr of more than 90 ml/min/1.73 m2. The house use of pesticides and exposure time were asked through a questionnaire. In this study 10072 participants enrolled, and 1079 remained in the final sample after appliance the exclusion criteria. Female sex, single marital status, low physical activity, TG more than 150 mg/dl, BMI of more than 25, non-smokers, house use of pesticide, and more time exposed to pesticides were associated with CKDu. The effects of age, female sex, TG more than 150 mg/dl, pesticide use (1.36;95%CI 1.01-1.84), and the third tertile of exposure time compared to non-users (1.64;95%CI 1.07-2.51) remained significant in multivariable analysis. We found a positive association between the use and exposure time with kidney function in cases without diabetes mellitus and hypertension. Further longitudinal studies should be carried out to assess this effect.

Metabolic syndrome (Mets) is a set of metabolic disorders including abdominal obesity, insulin resistance or disorders of glucose absorption and metabolism, lipid disorders, and hypertension, which increases the risk of chronic diseases including type 2 diabetes, cardiovascular diseases, cancer, and mortality. Therefore, the present study aimed to determine the trend of Mets and its components in Zahedan, a city located in South-East of Iran, from 2009 to 2017. A total of 761 individuals aged >20 years were followed from 2009 to 2017. The frequency of metabolic syndrome was measured at two-time points based on four criteria: International Diabetes Federation (IDF), National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATP III), Third Adult Treatment Panel (ATP III), and American Heart Association and the National Heart Lung and Blood Institute (AHA/NHLBI). The prevalence of Mets ranged from 16.6 (95% CI: 13.9 - 19.2) (ATP III) to 23.70% (95% CI: 20.6 - 26.6) (AHA/NHLBI) in 2009. Accordingly, it increased from 5.2% to 7.3% during the study period using different criteria such that the frequency of Mets varied from 21.8 (95% CI: 18.8 - 24.7) (ATP III) to 31.0% (95% CI: 27.7 - 34.3) (AHA/NHLBI) in 2017. The increasing trend was prominent among females, persons aged

Introduction: Nonthyroidal illness syndrome (NTIS) is common in hemodialysis patients (HPs). However, limited clinical trials have been conducted in this field. Therefore, the aim of this study was to investigate the effect of Se and/or N-acetyl-cysteine (NAC) on NTIS parameters in HPs. Methods: In this factorial randomized controlled trial, 68 HPs were divided into four groups: group A received placebo of Se and NAC, group B received 600 μg per day of NAC and placebo of Se, group C received 200 μg of Se per day and placebo of NAC and group D received 200 μg of selenium and 600 μg of NAC per day for 12 weeks. Blood samples were taken at baseline and after 12 weeks to assess free tri-iodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), and reverse T3 (rT3) concentrations. Results: Our finding demonstrated that rT3 levels were decreased in B, C, and D groups and increased nearly to baseline levels in the A group after 12 weeks, with a marked difference between the groups (p < 0.001) based on ANOVA. Although there were no significant differences in FT3 (p = 0.39), FT4 (p = 0.76), and TSH (p = 0.71) between the groups at the end of the trial. Conclusion: This trial showed that Se and/or NAC exert beneficial effects on rT3 levels in HPs. However, long-term clinical trials with a larger sample size using more appropriate biomarkers are recommended to evaluate the efficacy and safety of Se and/or NAC in HPs.

Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00–5.53, p &lt, 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30–6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97–5.25, p &lt, 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62–4.09, p &lt, 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37–2.69, p &lt, 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

Objectives Apolipoprotein AIV has a role in chylomicrons and lipid secretion and catabolism. Also, Apo-AIV plays a role in the regulation of appetite and satiety. Previous studies on rats have shown that hyperthyroidism and hypothyroidism are associated with significant changes in Apo-AIV serum levels. There has been no research on serum Apo-AIV changes in hyper and hypothyroidism in humans. Methods This case-control study was performed on new patients with hyper and hypothyroidism. Eighteen patients with hyperthyroidism and 18 patients with hypothyroidism enrolled in the study. After 12 weeks treatment blood samples were recruited. If euthyroidism was achieved, serum Apo-AIV level was measured. Eighteen euthyroid healthy individuals without thyroid disease were chosen as the control group from general population. Results Serum levels of Apo-AIV before treatment in hypothyroidism, hyperthyroidism and in the control group were 85.61, 110.66 and 33.51 mg/dL respectively (p Conclusions The results of this study for the first time showed that the serum level of Apo-AIV is increased in patients with hyperthyroidism and is decreased in patients with hypothyroidism, and after treatment, there was a significant difference with the control group.

Aim Chronic inflammation and subsequent use of glucocorticoids can lead to relative adrenocortical insufficiency in patients with rheumatoid arthritis (RA). Previously, adrenocortical hormone, dehydroepiandrosterone (DHEA) was shown as a potential therapy for autoimmune disorders. However, data regarding effects of DHEA in RA are limited. The aim of this study was to investigate the effects of DHEA on quality of life (QOL) in premenopausal rheumatoid arthritis patients. Method In this randomized double blinded, controlled trial 46 premenopausal rheumatoid arthritis patients were assigned to receive 50 mg/d DHEA (23 patients) or placebo (23 patients) for 12 weeks. Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) questionnaire, visual analog score and swollen and tender joint counts (both 0-28) were used for assessment of disease activity. Persian-validated World Health Organization Quality of Life Brief version (WHOQOL BREF) questionnaire was used to assess quality of life. Results In comparison to the control group more improvement in QOL (P = .025) and environment health (P = .001) was observed in the DHEA group. After adjustment for age and disease duration DHEA was associated with more improvement in QOL (P = .01), psychological (P = .02) and physical health (P = .03). A trend toward a decrease in ESR was observed in DHEA group (P = .06). DAS was improved in both groups; however, there was no significant change in DAS28 between groups (P = .88). Frequency of adverse events albeit minor was similar in both groups. Conclusion Our study supports a slightly superior effect of DHEA over placebo to improve QOL in premenopausal female patients with rheumatoid arthritis. We did not find improvement in DAS in the DHEA group over placebo.

Rheumatoid arthritis has a non-homogeneous pattern around the world. The current study aimed to describe the clinical manifestations and disease activity of rheumatoid arthritis patients in southeastern Iran. In this descriptive, cross-sectional study with convenience sampling, data regarding the demographics, painful joints, number of swollen and tender joints, ESR, disease activity, and therapeutic regimen of 500 patients with rheumatoid arthritis who referred to the Rheumatology Clinic of Ali Ebn Abitaleb Hospital between October 2012 and October 2013 was collected using a data form. After collection, the data was analyzed using SPSS version 16. Of the 500 studied cases, 437 cases (87.4%) were female and 63 cases (12.6%) were male. Average patient age was 48.78 ± 13.97 years, and the mean duration of the disease was 7.28 ± 7.14 years. The mean value of disease activity score-28 (DAS-28) was 3.54 ± 1.38. The DAS-28 in 30.25% of cases was below 2.6, while in 14.7% of cases it was greater than 5.1. The knee (49.6%) and the wrist (36.6%) were the most prevalent painful joints, and 375 patients complained of morning stiffness. The most frequent therapeutic regimens were prednisolone (81%), methotrexate (62.4%), hydroxychloroquine(60.8%), sulfasalazine (24%), and non-steroidal anti-inflammatory drugs (NSAIDs) (22.2%). Based on the results of this study, the mean value of DAS-28 of 3.54 ± 1.38 implies disease activity in most cases in southeastern Iran. This indicates that changing therapy regimens is necessary.

Hashimoto's thyroiditis (HT) is a chronic inflammation of the thyroid gland and is known as the most common autoimmune disease. Development of autoimmune destruction of thyroid cells is a multi-step process involving convergence of genetic and environmental factors. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) has an important role in homeostasis and negative regulation of immune responses, and is therefore considered to be a key element in the development of autoimmune diseases. The present study evaluated the association of the CTLA-4 gene polymorphisms 318C/T (rs5742909) and +49A/G (rs231775) with HT in an Iranian population (including 82 patients with HT and 104 healthy controls who were referred for routine premarital blood screenings). Genotyping was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction technique. No significant differences were observed in genotype and allele frequencies in the single nucleotide polymorphisms (SNPs) between cases and controls. In the cases as well as in the controls, the TT genotype in the −318C/T polymorphism was absent and the predominant genotype was CC, while the predominant genotype for the +49A/G SNP was AA. As only few studies in this field have assessed Iranian and even Middle Eastern populations, additional studies with a higher number of samples are recommended to further assess the impact of −318C/T (rs5742909) and +49A/G (rs231775) polymorphisms of CTLA-4 on HT.

In addition to other factors regarding the disease susceptibility, genetic factors are the main causes of Hashimoto's thyroiditis (HT) disease. CTLA4 and PTPN22 are the most prominent genes involved in the immune system regulation, thus effective in the pathogenesis of autoimmune diseases. In the current study, the association of two polymorphisms of CTLA4 and PTPN22 genes, 1661A/G (CTLA-4 gene) and C1858T (PTPN22 gene), with HT was investigated by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) technique. The effects of -1661A/G and C1858T polymorphisms on the mRNA and protein structures of CTLA-4 and PTPN22 were investigated by an in silico analysis. There was no significant difference between the genotype and allele frequencies of PTPN-22 gene polymorphism (rs2476601) in case and control groups. There was a positive association between the frequency of heterozygous genotype of CTLA4-1661A/G polymorphism (rs4553808) and HT (P = .04), but no association was seen regarding allele frequencies. In-silico analysis predicted that the transition of allele A to allele G would lead to the loss of some of the binding sites. Also, the structural analysis of C1858T transition effect on protein revealed a significant influence on PTPN-22 function. Our results showed that heterozygous genotype of -1661A/G CTLA4 gene variation might be related with the risk of HT.

Vitamin D deficiency is a major health problem which affects about one billion people in the world. Although, vitamin D supplementation is recommended as standard treatment of vitamin D deficiency, there are controversies on dose response relationship. In this regard, the present study aimed to determine the impact of vitamin D3 supplement on raising of serum 25 hydroxyvitamin D[25(OH)D] in healthy subjects with varying degrees of vitamin D deficiency.In this clinical trial 114 subjects with varying degrees of vitamin D deficiency were entered and divided into three groups: serum levels of 25(OH) D less than 10 ng/ml, 10-20 ng/ml, and 20-30 ng/ml. All of the participants were given 50,000 units vitamin D3 per week for 8 weeks, thereafter, changes in serum levels of vitamin D and PTH were evaluated at week twelve. The results were analyzed using SPSS version 16 and P 0.05 was considered to be significant.Of the 114 vitamin D deficient subjects, serum level of vitamin D was below 10 ng/ml in 22 persons (19.3%), 10-20 ng/ml in 52 persons (45.6%) and 20-30 ng/ml in 40 persons (35.1%). Following vitamin D prescription all people with varying degrees of vitamin D deficiency obtained a favorable serum level. The increase in vitamin D levels were 26.4, 18.5, and 8.3 ng/ml, in individuals with baseline vitamin D levels below 10 ng/ml, 10-20 ng/ml and 20-30 ng/ml, respectively. The changes in 25(OH) vitamin D in all three groups were significant (P 0.05), nonetheless no significant alterations in serum levels of PTH were observed (P 0.05).Our results indicated an inverse relationship between baseline serum levels of 25(OH) D and its increment following treatment with vitamin D3. Therefore, the magnitude of increments in serum 25(OH) D is greater in subjects with lower baseline levels of 25(OH) D.

Ganglioneuroblastoma is a primary malignant tumor of the sympathetic nervous system. It usually occurs in children and is extremely rare in adults. Here, we report a case of an adrenal ganglioneuroblastoma in a 38-year-old man. The adrenal incidentaloma was surgically removed and pathologically diagnosed as a ganglioneuroblastoma. The characteristics were described, because it is an unusual tumor based on the published reports in adults. To the best of our knowledge, fewer than 50 cases of ganglioneuroblastoma and 19 cases of adrenal ganglioneuroblastoma, including this case, are reported in the literature.

Thyroid hormone biosynthetic defects are rare causes of congenital hypothyroidism. Although, initial presentations are usually diffuse goiter and hypothyroidism, subsequently they may develop thyroid nodules and or thyroid cancer. We describe a case of hypothyroidism due to dyshormonogenesis whose one of the previously solid nodules degenerates into a large cyst. A 22-year-old male was referred to our clinic for evaluation of enlarging thyroid nodule. Hypothyroidism was diagnosed in infancy, however due to poor compliance to treatment TSH values were elevated most of the times. When he was fifteen the first nodule was detected which was a solid cold nodule. Fine needle aspiration was in favor of benign follicular nodule. Seven years later we found a large multi nodular thyroid with a predominant large cyst corresponding to the previously detected solid nodule. 21cc straw colored fluid was aspirated. Cytology was reported as benign cystic nodule. The patient underwent thyroidectomy and pathology confirmed a benign thyroid cyst. Although underreported thyroid dyshormonogenesis may progress to cystic degeneration. Taking into account the risk of malignancy and eventually cyst formation, we recommend more frequent evaluation in the face of nodule formation in these patients. Arq Bras Endocrinol Metab. 2014;58(9):958-61

The rs2235306 of apelin polymorphism has been shown to be associated with fasting plasma glucose levels and hypertension. The present study aimed to investigate the impact of the apelin rs2235306 gene polymorphism on the risk of metabolic syndrome (MeS) in a sample of the Iranian population. Materials and methods: This population-based cross-sectional study was performed on 151 subjects with MeS and 149 without MeS, as defined by ATPIII criteria. Apelin rs2235306 polymorphism detection was done using the tetra amplification refractory mutation system-polymerase chain reaction. Because the apelin gene is located on the X chromosome, statistical analyses were conducted in a sex-specific manner. Results: Our findings proposed that the apelin rs2235306 polymorphism was not associated with MeS susceptibility in the codominant, dominant, and recessive inheritance models tested (OR = 0.93, 95% CI = 0.51-1.71 for TC vs. TT; OR = 2.39, 95% CI = 0.70-8.16 CC vs. TT; OR = 1.09, 95% CI = 0.62-1.93 for TC+CC vs. TT; and OR = 2.45, 95% CI = 0.73-8.21 for CC vs. TT+TC). We found that the apelin TC+CC genotypes were associated with lower HDL-cholesterol in women without MeS. Conclusion: Our findings indicated no association between the apelin rs2235306 polymorphism and MeS. However, the results suggest that healthy females carrying apelin TC+CC genotypes have lower HDL-cholesterol in comparison with those carrying TT, which remains to be confirmed.

Background Efficient treatment of skin ulcers, a leading cause of substantial number of morbidities among diabetic patients, is a subject of matter. Objectives Since current therapies are partially effective and/or expensive and topical liothyronine (T3) was shown to get faster wound healing in mice, the present study was designed to assess its effectiveness in diabetic male rats. Materials and Methods In this experimental study, 30 male wistar rats with mean weight of 242 g were randomly assigned into control (group C) (n = 10) and diabetic (n = 20) groups. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin. Diabetic rats were randomly subdivided into two groups: diabetic T3 group (group A) which was treated with 150 ng/day topical T3 and diabetic placebo group (group B) received vehicle. Full thickness wound on dorsum was created in each rat (1 cm2). Photographs were taken at baseline, fourth and tenth day to analyze changes in surface areas of wounds. Results Results obtained from the present study showed that baseline surface areas of wounds were similar in all groups. Conversely, wound contraction was significantly better in T3 group in fourth and tenth days compared to placebo group, (P = 0.001, P < 0.00001). Moreover, wound healing was impaired in diabetic placebo group compared to other groups (all P < 0.05). Conclusions This study revealed that topical T3 administration is an effective measure for treatment of ulcers in diabetic male rats.

article i nfo Metabolic syndrome (MeS) is associated with increased risk for type 2 diabetes mellitus (T2DM) and cardio- vascular disease. There is some evidence indicating that adipokines play a role in the development of MeS. The present study was aimed to investigate the impact of chemerin rs17173608 and vaspin rs2236242 gene polymorphisms with the risk of MeS in a sample of Iranian population. This case-control study was done on 151 subjects with MeS and 149 without MeS, as defined by NCEP-ATPIII. Tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was designed to de- tect the polymorphisms. Our finding showed that there are significant differences in genotype frequencies be- tween the groups regarding vaspin rs2236242 polymorphism (χ 2 =18.74, pb0.0001). A significant protection against MeS was found for vaspin rs2236242 in allele and genotypes (Odd Ratio (OR)=0.52; 95% confidence interval (CI)=0.37-0.72; p=0.0001, T vs A; OR=0.49; 95%CI=0.29-0.82; p=0.007, TT vs TA and OR= 0.17; 95%CI=0.07-0.40; pb0.0001, TT vs AA). Our finding showed positive association between chemerin rs17173608 polymorphism and risk of MeS (χ 2 =7.70, p=0.021). The G allele increased the risk of MeS (OR=1.78; 95% CI=1.14-2.78; p=0.012) as compared to the T allele. In conclusion, our data suggest for the first time a significant association between vaspin rs2236242 and chemerin rs17173608 polymorphisms and the MeS in Zahedan, southeast Iran. Further studies with large sample size and different ethnicities are re- quired to confirm our findings.

Aim: Genetic and environmental factors are risk factors for breast cancer. Our aim was to investigate the associations between genetic polymorphism of GST genes (GSTM1, GSTT1 and GSTP1) and susceptibility to breast cancer in an Iranian population. Materials & methods: This case–control study was carried out on 134 patients with breast cancer and 152 healthy, cancer-free women. GSTP1 polymorphism was determined using tetra-primer amplification refractory mutation system PCR assay and GSTM1 and GSTT1 were genotyped by a multiplex PCR. Results: We found that the GSTM1 null genotype is a risk factor for predisposition to breast cancer (odds ratio [OR] = 2.01; 95% CI = 1.78–3.45; p = 0.010). No significant difference was found between the groups regarding GSTT1 null genotype (p > 0.05). The GSTP1 Ile/Val and Val/Val genotypes were associated with breast cancer risk (OR = 3.29; 95% CI = 1.84–5.91; p < 0.0001 and OR = 20.68; 95% CI = 5.66–75.60; p < 0.0001, respectively). Conclusion: In summary, GSTM1 and GSTP1, but not GSTT1 genetic polymorphisms are associated with increased risk of breast cancer in our population.

Metabolic syndrome (MeS), a cluster of several metabolic disorders, is increasingly being recognized as a risk factor for type II diabetes (T2D) and cardiovascular disease. Genetic and epigenetic alteration of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) has been associated with components of MeS. The aim of the present study was to investigate the possible association of a 32-bp deletion polymorphism and promoter methylation of the PTEN gene with MeS. DNA was extracted from the peripheral blood of 151 subjects with and 149 subjects without MeS. The 32-bp deletion variant of PTEN was detected by polymerase chain reaction (PCR) and PTEN promoter methylation was defined by a nested methylation‑specific PCR (MSP) method. No significant differences were found in the allelic and genotypic frequencies of the 32-bp deletion variant of PTEN between the groups [odds ratio (OR), 0.77; 95% confidence interval (CI), 0.41-1.45; P=0.431]. However, patients with MeS were identified to have lower levels of PTEN promoter hypermethylation than subjects without MeS. Promoter methylation may be a protective factor against susceptibility to MeS (OR, 0.52; 95% CI, 0.29-0.92; P=0.029). Our findings suggest that PTEN promoter methylation may be a mechanism for PTEN downregulation or silencing in MeS, which remains to be fully clarified.

Background: Several studies show a high prevalence of vitamin D deficiency in Asia. Data regarding the prevalence of vitamin D deficiency in southeast Iran are inadequate. Objectives: The purpose of this study was to determine the prevalence of vitamin D deficiency in Zahedan, a sunny area in southeast Iran. Subjects and Methods: This population-based cross-sectional study was performed on 993 apparently healthy subjects. Serum levels of 25-hydroxy vitamin D (25-OH vit D), parathyroid hormone, calcium, phosphate, and alkaline phosphatase activity were measured. Results: Inadequate vitamin D status was diagnosed in 94.7% of the subjects (25-OH vit D 150 ng/ml) were 85.2, 9.5, 5.3, and 0.0%, respectively. Conclusion: The results indicate that vitamin D deficiency is common in the population of Zahedan. Based on our results, fortification of milk and the use of supplements is suggested in this region.

Thiopurine S-methyltransferase (TPMT, EC 2.1.1.67) plays a key role in the metabolism of thioprine drugs. Subjects with intermediate or no TPMT activity are at risk of azathioprines toxicity treated with conventional dosages of thiopurine drugs. While TPMT polymorphisms have been extensively studied in many countries, there is insufficient data in Iranian populations. In the present study, we aimed to identify the common functional TPMT alleles in southeast Iranian population. The TPMT allele frequencies were determined by multiplexed allele-specific polymerase chain reaction. Among 832 samples of Iranian population, the frequency for the TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C, were 2.16%, 1.68%, 1.62%, and 0.54%, respectively. The distribution of the TPMT genotypes were 87.98% for TPMT*1/*1, 4.33% for TPMT*1/*2, 3.36% for TPMT*1/*3A, 3.24% for TPMT*1/*3B, and 1.08% for TPMT*1/*3C. This functional analysis of common TPMT alleles in an Iranian population could provide useful information for thioprine drugs therapy.

The enterohepatic circulation of thyroid hormones is increased in thyrotoxicosis. Bile-salt sequestrants bind thyroid hormones in the intestine and thereby increase their fecal excretion. Based on these observations, the use of cholestyramine has been tried. The present study evaluates the effect of low doses of cholestyramine as an adjunctive therapy in the management of hyperthyroidism. In a prospective, randomized, double-blind, placebo-controlled trial, 45 patients with newly diagnosed hyperthyroid Graves’ disease were randomly assigned into the following treatment protocols: group I, cholestyramine 2 g BID, methimazole and propranolol; group II, cholestyramine 1 g BID, methimazole and propranolol; group III, placebo powder, methimazole and propranolol. The fixed dose of methimazole (30 mg/d) and propranolol (40 mg/d) was used. The study period was 4 weeks. Serum total triiodothyronine and free thyroxin were measured at baseline, and at the ends of the second and the fourth week of the study. The serum thyroid hormone levels decreased more rapidly and to a greater extent in the cholestyramine-treated groups. All of the patients in group I had achieved euthyroid state at the end of the study. We conclude that low dose of cholestyramine is an effective and well-tolerated adjunctive agent in the treatment of hyperthyroid Graves’ disease. (ClinicalTrials.gov number, NCT00677469)

Introduction: Imatinib, a tyrosine kinase inhibitor which resulted in much improvement in the treatment of chronic myelogenous leukemia (CML), may adversely affect thyroid gland function. To date, assessment of thyroid function during imatinib therapy has limited to retrospective studies. The aim of this study was to evaluate the effects of imatinib on thyroid function in a prospective manner. Materials and Methods: In this prospective study, 16 newly diagnosed adult subjects with positive Philadelphia chromosome in chronic phase of CML without any other apparent underlying diseases were enrolled. Free T3, Free T4, TSH, Anti TPO and Anti thyroglobulin antibodies were measured before and after 4 and 12 weeks of treatment. Results: Of the 16 patients, 9 were male (57.1%) and 7(42.9%) were female with a mean age of 29±5 years. There were statistically significant changes within reference ranges in serum concentrations of TSH (P=0.753 and 0.002), Free T3 (P=0.012 and 0.007) and Anti Thyroglobulin (P=0.221 and 0.041) 1 month before and 3 months after imatinib initiation, respectively. At the same time, there were no significant changes in serum Free T4 (P=0.196 and 0.650) and Anti TPO (P=0.807 and 0.600) concentrations. Conclusion: This study showed some significant changes on thyroid function tests during imatinib therapy. However, all of them were within the normal range without any clinical abnormalities in the course of treatment. We recommend other studies with larger sample size and longer duration of follow-up.

Background: It has been proposed that the patients with mitochondrial diseases usually manifest systemic metabolic disorders. The metabolic syndrome (MeS), a cluster of several metabolic disorders, is increasingly being recognized as a risk factor for type 2 diabetes (T2D) and cardiovascular disease. Objectives: The aim of study was to investigate the possible association between promoter methylation of mitochondrial transcription factor A (TFAM) and MeS. Patients and Methods: DNA was extracted from peripheral blood of 151 patients with and 149 without MeS. Results: TFAM promoter methylation was evaluated by a nested methylation-specific PCR (nested MSP). Conclusions: No association was found between TFAM promoter methylation and MeS. The present study suggests that the TFAM promoter methylation is not associated with risk of MeS.

Background Metabolic syndrome (MeS) is being recognized as a risk factor for insulin resistance and cardiovascular disease. The present study was aimed to find out the possible association between 45-bp I/D polymorphism of uncoupling protein 2 (UCP2) and MeS. Methods DNA was extracted from peripheral blood of 151 subjects with and 149 subjects without MeS. 45-bp I/D variant of UCP2 was detected using polymerase chain reaction (PCR). Results Our finding showed that 45-bp I/D polymorphism was associated with protection against MeS (OR = 0.56, 95% CI = 0.34-0.92, p = 0.020 D/I vs DD and OR = 0.54, 95% CI = 0.34-0.86, p = 0.009; D/I + I/I vs D/D). The I allele decreased the risk of MeS (OR = 0.62, 95% CI = 0.44-0.90, p = 0.011) in comparison with D allele. Conclusion In conclusion, our result suggests that 45-bp I/D polymorphism is associated with the risk of MeS, which remains to be cleared.

Background and study aims Coeliac disease (CD) may be associated with several liver disorders including primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Furthermore preliminary data suggest a causative role of CD in steatosis and steatohepatitis. The aim of present study was to determine the prevalence of CD in a series of patients with non-alcoholic fatty liver disease (NAFLD). Patients and methods In a cross sectional study (2008–2010), 403 consecutive NAFLD patients (127 female and 276 male) referred to GI clinics of the Zahedan University of Medical Sciences were included. IgA anti-tissue transglutaminase (Anti-tTG) was used for screening of coeliac disease. In the patients with a positive serologic test, duodenal biopsies were taken to confirm the diagnosis. Results The mean ± SD of the age and BMI of patients were 37.4 ± 12.4 years and 28.3 ± 4.15 kg/m 2 respectively. BMIs lower than 25 kg/m 2 were found in 58 subjects (14.5%). Furthermore diabetes mellitus and hyperlipidaemia were diagnosed in 48 (11.9%) and 84 (20.8%) individuals respectively. Positive Anti-tTGs were found in 14/403 (3.4%) and 13/403 (3.2%, 95% CI 1.5–4.9) had coeliac disease according to the modified Marsh classification; 8 had type I, 3 type II, 1 type IIIA and 1 type IIIB lesions. Conclusion According to our data, prevalence of CD in the subjects with NAFLD is higher than the rates reported in the general population. Therefore screening for CD in selected cases of NAFLD may be appropriate.

Introduction Immune thrombocytopenia (ITP) is an immune disorder commonly presents as isolated thrombocytopenia. Generally corticosteroids are the main treatment of ITP. This study was designed to evaluate effectiveness of high dose dexamethasone comparing conventional corticosteroid therapy in the treatment of ITP. Materials and methods In a randomized prospective study, sixty adult patients with newly diagnosed primary symptomatic ITP (Platelet count

Methotrexate is an antifolate medication frequently used in the treatment of malignant and nonmalignant diseases. The usage of high-dose methotrexate was limited to patients with osteosarcoma, Ewing sarcoma, lymphoma, and acute lymphoblastic leukemia. One of the major side effects of high-dose methotrexate is nephropathy. The aim of present study was to determine the renal side effects of high-dose methotrexate in patients with malignancies.In a study of 102 patients with osteosarcoma (n = 72), Ewing sarcoma (n = 15), and lymphoma (n = 15), treated with high-dose methotrexate, clinical and laboratory data including kidney function tests were recorded at baseline and during follow-up visits. The mean duration of follow-up was 6 months.The mean age of the patients was 19.5 years (range, 5 to 80 years). The total courses of methotrexate therapy were 273 (median, 2.67 per patient). The mean creatinine level was 0.82 mg/dL. Of the 102 patients, 3 (2.9%) developed acute kidney injury with an at risk phase. Another patient (1.0%) developed acute kidney injury and its phase was injury according to the RIFLE criteria. None of the cases were failed and acute kidney injury was alleviated in all of the affected patients.Our data revealed a low prevalence of acute kidney injury with high-dose methotrexate therapy. In addition, these toxicities were limited to the first and second phases of the RIFLE classification, all of which resolved spontaneously.

Background and study aims Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder and coeliac disease (CD) is an auto-immune enteropathy that can mimic almost any functional GI disorder. Both IBS and coeliac disease share common symptoms. The aim of the present study was to estimate the prevalence of CD in patients with IBS and its sub-types. Patients and methods In this cross-sectional study (2008–2010), all consecutive patients with IBS who fulfilled the Rome III criteria attending the GI units in Zahedan (Southeast Iran) were included. Patients based on the sub-type of IBS were classified as diarrhoea-predominant irritable bowel syndrome (D-IBS), constipation-predominant irritable bowel syndrome (C-IBS) and alternating symptoms (mixed type). Immunoglobulin A (IgA) tissue transglutaminase (anti-tTG) was used to screen patients for CD. In the case of positive serologic test, duodenal biopsies were taken to confirm the diagnosis. Results A total of 364 (221 females and 143 males) patients with IBS were included. The mean ± standard deviation (SD) age of patients was 37.4 ± 12.4 years. Twenty (5.5%) patients were found to have positive IgA anti-tTG. Main symptoms of patients were diarrhoea (11/20), bloating (10/20) and abdominal distension (6/20). Thirteen (10.5%) patients were found to have positive IgA anti-tTG among the D-IBS, two (1.6%) in the C-IBS and five (4.2%) in M-IBS groups. Conclusion The prevalence of CD in IBS is high. IBS subjects whose main complaint is diarrhoea, bloating or even abdominal distension should be evaluated for CD.

ObjectiveParaoxonase (PON) is associated with high-density lipoprotein and protects serum lipid from oxidation. The aim of this study was to determine serum PON, arylesterase (ARE) activities, and total antioxidant capacity (TAC) in metabolic syndrome (MES).MethodsThis case–control study was performed on 106 patients with MES and 231 healthy subjects. Serum PON and ARE activities were determined spectrophotometrically. TAC was determined using ferric reducing ability of plasma assay.ResultsThe results showed that serum PON activity was significantly lower in patients with MES (69.62±59.86 IU/l) than healthy subjects (91.64±77.45 IU/l) (PPConclusionThe lower PON and ARE activities in MES may be considered an independent risk factor for cardiovascular disease, which remains to be cleared.

Paraoxonase-1 (PON1), a high-density lipoprotein (HDL) associated enzyme, is involved in the metabolism and detoxification of insecticides and pesticides. Three polymorphisms within the PON1 gene affect the enzyme activity. Two of these (L55M and Q192R) are located at the coding region and the third (–107C/T) is in promoter region. We performed a case–control study in order to elucidate the possible contribution of variability within PON1 at three mentioned positions to the risk of MS in a South-East Iranian population. DNA was isolated from peripheral blood of patients (N = 119) with MS and healthy controls (N = 201). Allelic polymorphisms at positions Q192R, L55M and –107C/T in the PON1 gene were studied by Amplification Refractory Mutation System (ARMS)-PCR. It was observed that genotypes RR and QR + RR of Q192R locus significantly increased the risk of MS (OR = 2; 95% CI: 1.17–3.40, P = 0.0001 and OR = 1.62; 95% CI: 1.0–2.63; P = 0.05, respectively). The risk in patients with MM and LM + MM genotypes at the L55M locus was marginal (OR = 1.33; 95% CI: 0.68–1.85; P = 0.34 and OR = 1.12; 95% CI: 0.68–1.85; P = 0.73 respectively). The CC genotype at –107C/T locus also increased the risk of metabolic syndrome, but was not significant. This association was somewhat stronger when combined genotypes at Q192R and L55M loci were analyzed (OR = 3.30; 95% CI: 1.34–8.24; P = 0.007). Our results, in this first study, provide evidence for association of PON1 gene polymorphisms with the risk for metabolic syndrome.

Background: Endocrinopathies and diabetes mellitus are prevalent in patients with beta-thalassemia major Recently some studies demonstrate a link between low levels of serum zinc level and higher prevalence of diabetes. The aim of this study was to evaluate the glucose tolerance in patients suffered from beta-thalassemia major and determine the association of Homeostasis Model Assessment (HOMA) parameters with zinc status among these patients. Materials and Methods: In this cross sectional study, clinical data of patients who were suffered from thalassemia major, aged≥10 years were collected. Serum ferritin concentration, fasting blood sugar, fasting blood insulin and serum zinc level were assessed after overnight fasting. Moreover, oral glucose tolerance test was performed. Homeostasis Model Assessment (HOMA-2) was used for calculating beta-cell function, insulin resistance and sensitivity for normoglycemic and pre-diabetic subjects. Results: of the 163 patients diagnosed with beta-thalassemia major, 10%, 53% and 37% were diabetic, pre-diabetic and normal, respectively. Mean serum zinc concentration was equal to 18.90±10.93µg/dl, and it was not significantly different across diabetic, pre-diabetic and normal groups. Pre-diabetic patients had significantly lower beta-cell function compared to normal subjects (P=0.0001). An inverse relation was documented between beta-cell function on one hand and total units of blood transfusion and ferritin level on the other hand (r=-0.29, P=0.004 and r=-0.27, P=0.03, respectively). The analysis adjusted for multiple possible confounders showed that there is no significant association between HOMA parameters and serum zinc level. Conclusion: Impaired glucose metabolism and low serum zinc level were quite common among our study participants. The findings of the study also signifies the substantial role of follow-up in early detection and appropriate treatment.