The effects of Ellagic acid supplementation on neurotrophic, inflammation, and oxidative stress factors, and indoleamine 2, 3-dioxygenase gene expression in multiple sclerosis patients with mild to moderate depressive symptoms: A randomized, triple-blind, placebo-controlled trial.

BACKGROUND: Depression is one of the most common psychological disorders among multiple sclerosis (MS) patients that characterized as the first symptoms. Ellagic acid is a natural polyphenol that may have neuroprotective properties through antioxidant, anti-inflammatory, and immunomodulatory effects. PURPOSE: The aim of the present study was to investigate the effects of Ellagic acid on circulating levels of brain derived neurotrophic factor (BDNF), interferon-γ (IFN-Æ´), nitric oxide (NO), nuclear factor erythroid-2-related factor 2 (Nrf2), cortisol, serotonergic system, and indoleamine 2, 3-dioxygenase (IDO) gene expression in MS patients with mild to moderate depressive symptoms. STUDY DESIGN: A randomized triple-blind clinical trial. METHODS: The eligible patients according to the inclusion criteria were randomly divided into two groups: either 180 mg Ellagic acid (Axenic company) (n = 25) or 180 mg maltodextrin (n = 25) group for 12 weeks. The Ellagic acid supplement were identical to placebo in shape, color and odor. Serum BDNF, NO, Nrf2, cortisol, serotonin, and IFN-Æ´ were measured by ELISA kit in the baseline and end of the study. Also, demographic characteristics, anthropometric measurements, physical activity, food intake, Beck Depression Inventory-II (BDI-II) and expanding disability status scale (EDSS) questionnaires, as well as IDO gene expression were assessed. SPSS software version 24 was used for statistical analysis. RESULTS: Fifty patients were evaluated, and a significant decrease in BDI-II (p = 0.001), IFN-Æ´ (p = 0.001), NO (p = 0.004), cortisol (p = 0.015), IDO gene expression (p = 0.001) and as well as increased the level of BDNF (p = 0.006) and serotonin (p = 0.019) was observed among those who received 90 mg Ellagic acid twice a day for 12 weeks versus control group. However, there were no significant differences between groups for Nrf2 levels (p>0.05) at the end of study. CONCLUSION: The current study indicates that Ellagic acid intervention has a favorable effect on depression in MS patients. This is achieved by reducing BDI-II scores, as well as levels of NO, cortisol, IFN-Æ´, and IDO gene expression. Furthermore, we found a significant elevation in circulating levels of BDNF and serotonin.

Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: a multicentral-triple blind randomized clinical trial.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines. Methods: The present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-ß), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method. Findings: Ellagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (-24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; -5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; -18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-ß in any of the study groups (p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores (p < 0.05), and no significant changes observed in PRI score (p > 0.05). Conclusion: Ellagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression.Clinical trial registration: (https://en.irct.ir/trial/53020), IRCT20120415009472N22.

The effects of chitosan supplementation on anthropometric indicators of obesity, lipid and glycemic profiles, and appetite-regulated hormones in adolescents with overweight or obesity: a randomized, double-blind clinical trial.

BACKGROUND: Chitosan is one of dietary fiber that has received great attention in improving obesity-related markers, but little is known on its effects on adolescents. OBJECTIVES: To analyze the effects of chitosan supplementation on obesity-related cardiometabolic markers and appetite-related hormones in adolescents with overweight or obesity. METHODS AND ANALYSIS: A randomized clinical trial was performed on 64 adolescents with overweight and obesity, who were randomly allocated to receive chitosan supplementation (n = 32) or placebo as control (n = 32) for 12 weeks. Anthropometric measures, lipid and glycemic profiles, and appetite-related hormones were examined. RESULTS: Sixty-one participants completed study (chitosan = 31, placebo = 30). Chitosan supplementation significantly improved anthropometric indicators of obesity (body weight: - 3.58 ± 2.17 kg, waist circumference: - 5.00 ± 3.11 cm, and body mass index: - 1.61 ± 0.99 kg/m2 and - 0.28 ± 0.19 Z-score), lipid (triglycerides: - 5.67 ± 9.24, total cholesterol: - 14.12 ± 13.34, LDL-C: - 7.18 ± 10.16, and HDL-C: 1.83 ± 4.64 mg/dL) and glycemic markers (insulin: - 5.51 ± 7.52 µIU/mL, fasting blood glucose: - 5.77 ± 6.93 mg/dL, and homeostasis model assessment of insulin resistance: - 0.24 ± 0.44), and appetite-related hormones (adiponectin: 1.69 ± 2.13 ng/dL, leptin - 19.40 ± 16.89, and neuropeptide Y: - 41.96 ± 79.34 ng/dL). When compared with the placebo group, chitosan supplementation had greater improvement in body weight, body mass index (kg/m2 and Z-score), waist circumference, as well as insulin, adiponectin, and leptin levels. Differences were significant according to P-value < 0.05. CONCLUSION: Chitosan supplementation can improve cardiometabolic parameters (anthropometric indicators of obesity and lipid and glycemic markers) and appetite-related hormones (adiponectin, leptin, and NPY) in adolescents with overweight or obesity.

Effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus: A randomized clinical trial.

Background: Vascular dysfunction is a major complication of diabetes mellitus that leads to cardiovascular disease (CVD). This study aimed to examine the effects of omega-3 consumption on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus (T1DM). Methods: In this randomized, double-blind, placebo-controlled clinical trial, 51 adolescents (10-18 years) with T1DM completed the study. Patients received 600 mg/day [containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA)] of omega-3 or placebo for 12 weeks. Flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, blood urea nitrogen (BUN), creatinine, fasting blood sugar (FBS), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), serum insulin (SI), urine albumin-creatinine ratio (uACR), blood pressure, and anthropometric indices were assessed at the baseline and after the intervention. Results: Following supplementation, omega-3 significantly increased FMD (3.1 ± 4.2 vs. -0.6 ± 4%, p = 0.006) and decreased TG (-7.4 ± 10.7 vs. -0.1 ± 13.1 mg/dl, p = 0.022) in comparison with the placebo group. However, no significant difference was observed regarding CIMT (-0.005 ± 0.036 vs. 0.003 ± 0.021 mm, p = 0.33). Although hs-CRP was significantly decreased within the omega-3 group (p = 0.031); however, no significant change was observed compared to placebo group (p = 0.221). Omega-3 supplementation had no significant effect on other variables. Conclusion: Given the elevation in FMD and reduction in TG, omega-3 supplementation can improve vascular function and may reduce the risk of cardiovascular disease in adolescents with T1DM patients.

First Record of Black Widow Spider Bite Latrodectus cinctus (Araneae: Theridiidae) From Iran.

The genus Latrodectus contains the most medically important spiders around the world. This study describes the first case of Latrodectus cinctus Blackwall, 1865 bite and clinical treatment from Iran. Also, it is the first collection report from the southeast of the country that can enhance prior knowledge on the geographical distribution of this species. We describe a 42-year-old female patient with neurological pain caused by the spider bite. Also, a summary of the entomological survey and morphological identification of the collected species from the patient's house is presented.

Study protocol of a randomized controlled clinical trial investigating the effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes.

BACKGROUND: Type 1 diabetes is a main health burden with several related comorbidities. It has been shown that endothelial function, vascular structure, and metabolic parameters are considerably disrupted in patients with type 1 diabetes. Omega-3 as an adjuvant therapy may exert profitable effects on type 1 diabetes and its complications by improving inflammation, oxidative stress, immune responses, and metabolic status. Because no randomized clinical trial has examined the effects of omega-3 consumption in children and adolescents with type 1 diabetes; the present study aims to close this gap. METHODS: This investigation is a randomized clinical trial, in which sixty adolescents with type 1 diabetes will be randomly assigned to receive either omega-3 (600 mg/day) or placebo capsules for 12 weeks. Evaluation of anthropometric parameters, flow-mediated dilation (FMD) as an endothelial function marker, carotid intima-media thickness (CIMT) as a vascular structure marker, proteinuria, biochemical factors including glycemic and lipid profile, blood urea nitrogen (BUN), creatinine, high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR), as well as blood pressure will be done at the baseline and end of the trial. Also, dietary intake and physical activity will be assessed throughout the study. Statistical analysis will be performed using the SPSS software (Version 24), and P < 0.05 will be considered statistically meaningful. DISCUSSION: It is hypothesized that omega-3 supplementation may be beneficial for the management of type 1 diabetes and its complications by reducing inflammation and oxidative stress and also modulating immune responses and glucose and lipid metabolism through various mechanisms. The present study aims to investigate any effect of omega-3 on patients with type 1 diabetes. ETHICAL ASPECTS: This trial received approval from Medical Ethics Committee of Iran University of Medical Sciences, Tehran, Iran (IR.IUMS.REC.1400.070). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20210419051010N1 . Registered on 29 April 2021.

Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS. METHODS: In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements. RESULTS: Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial. CONCLUSIONS: Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.

Comparing the effectiveness of vitamin D plus iron vs vitamin D on depression scores in anemic females: Randomized triple-masked trial.

Background: Low levels of 25-hydroxyvitamin D (25(OH)D) have been related to depression and anxiety. It seems that anemia is associated with vitamin D deficiency. We aimed to evaluate the effects of iron-vitamin D co-supplementation versus vitamin D alone on depression scores in anemic females with low levels of serum 25-hydroxyvitamin D. Methods: This randomized controlled trial was conducted on eighty premenopausal females who were recruited between May 2015 and October 2015 from primary health care centers. Women with anemia and low concentrations of 25(OH)D were randomized to either 1000 IU/d vitamin D plus 27 mg/d iron (D-Fe) or vitamin D plus placebo supplements (D-P) for 12 weeks. Depressive and anxious symptoms were evaluated with the Beck Depression Inventory (BDI) with subscales 1-13 and 14-21 and Beck Anxiety Inventory (BAI). To compare the groups, Mann-Whitney or chi-squared tests were used and within groups comparison was performed using Wilcoxon signed ranks test. The study was registered on www.clinicaltrial.org as NC 01876563. Results: The serum concentrations of 25(OH)D were increased significantly in both groups at the end of the study. In both groups, there was a significant improvement in total BDI, the BDI subscale, and the BAI scores (p<0.001). No differences were found between groups (p>0.05). Conclusion: Although the potential positive effect of vitamin D on mental health was evident, iron plus vitamin D co-supplementation did not demonstrate any significant benefits over vitamin D alone, neither in depression score reduction nor anxiety symptoms.

Health Care Expenditure and GDP in Oil Exporting Countries: Evidence From OPEC Data, 1995-2012.

BACKGROUND: There is a large body of literature examining income in relation to health expenditures. The share of expenditures in health sector from GDP in developed countries is often larger than in non-developed countries, suggesting that as the level of economic growth increases, health spending increase, too. OBJECTIVES: This paper estimates long-run relationships between health expenditures and GDP based on panel data of a sample of 12 countries of the Organization of the Petroleum Exporting Countries (OPEC), using data for the period 1995-2012. PATIENTS & METHODS: We use panel data unit root tests, cointegration analysis and ECM model to find long-run and short-run relation. This study examines whether health is a luxury or a necessity for OPEC countries within a unit root and cointegration framework. RESULTS: Panel data analysis indicates that health expenditures and GDP are co-integrated and have Engle and Granger causality. In addition, in oil countries that have oil export income, the share of government expenditures in the health sector is often greater than in private health expenditures similar developed countries. CONCLUSIONS: The findings verify that health care is not a luxury good and income has a robust relationship to health expenditures in OPEC countries.

Comparison of auditory temporal resolution between monolingual Persian and bilingual Turkish-Persian individuals.

OBJECTIVE: The aims of this study were to prepare a Persian version of the temporal resolution test using the method of Phillips et al (1994) and Stuart and Phillips (1996), and to compare the word-recognition performance in the presence of continuous and interrupted noise as well as the temporal resolution abilities between monolingual (ML) Persian and bilingual (BL) Turkish-Persian young adults. DESIGN: Word-recognition scores (WRSs) were obtained in quiet and in the presence of background competing continuous and interrupted noise at signal-to-noise ratios (SNRs) of -20, -10, 0, and 10 dB. STUDY SAMPLE: Two groups of 33 ML Persian and 36 BL Turkish-Persian volunteers participated. RESULTS: WRSs significantly differed between ML and BL subjects at four sensation levels in the presence of continuous and interrupted noise. However, the difference in the release from masking between ML and BL subjects was not significant at the studied SNRs. CONCLUSIONS: BL Turkish-Persian listeners seem to show poorer performance when responding to Persian words in continuous and interrupted noise. However, bilingualism may not affect auditory temporal resolution ability.