A systematic review and meta-analysis on the epidemiology, casual agents and demographic characteristics of onychomycosis in Iran.

Onychomycosis or fungal nail infection is one of the most common fungal infections. Nearly 50% of all nail disorders are caused by fungi. This systematic review and meta-analysis was conducted to determine the prevalence of onychomycosis across Iran. We searched English and Persian databases for studies reporting the epidemiologic features of onychomycosis in Iranian people from January 2000 to December 2018. Literature search revealed 307 studies, of which 24 studies met the eligibility criteria. In order to identifying the existence of publication bias among studies, funnel plots were used. The results of the meta-analysis were visualized as a forest plot representing the prevalence estimates of each study. Heterogeneity was also analyzed using the I2, Chi2, and Tau2 statistics. A high level of I2 and Chi2 was obtained among studies, which provides evidence of notable heterogeneity between studies. The results of current study revealed that the highest prevalence of onychomycosis was related to Mazandaran and Tehran provinces, respectively. As in the literature hypothesized shift in etiologic agents from yeasts to dermatophytes or molds could not be confirmed. Females were affected more frequently than males and in both sexes the highest incidence of infection occurrence was at the ages of >50 years. It seems the highest prevalence of onychomycosis in Mazandaran and Tehran provinces is due to the concentration of specialist doctors and research centers in these two provinces compared with others which leads to more detection and more care of the disease. Therefore, further educational strategies in order to accurate diagnosis in other provinces is necessary to reduce the risk of onychomycosis in Iran.

Immunoregulation of Inflammatory and Inhibitory Cytokines by Vitamin D3 in Patients with Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of vitamin D3 in patients with IBD exerts both direct and indirect regulatory roles on the naïve T cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of vitamin D3 on naïve T cells result in the proliferation of more regulatory T cells and inhibitory cytokines such as IL-4, IL-10 and IL-5. The binding of vitamin D to dendritic cells (DCs) through vitamin D receptors inhibits the action of IL-12 on DCs, resulting in the downregulation of Th1 and Th17. On the other hand, this interaction favours Th2 and Treg upregulation and facilitates the maintenance of immune homoeostasis between inflammatory and inhibitory cytokines which is essentially significant in the management of patients with IBD. The aim of this review was to explore the current and mounting scientific evidence on the roles of vitamin D3 in immunoregulation of inflammatory and inhibitory cytokines in patients with IBDs. An extensive literature search was conducted using keywords such as Vitamin D3*, IBD*, inflammatory cytokines*, inhibitory cytokines*, naïve-T-cells* and antigen presenting cells* through PubMed, SCOPUS and MEDLINE search engines. The results of the accumulated bodies of research that have been conducted demonstrate that vitamin D3 plays a major role not only in the immunoregulation of cytokines involved in the pathogenesis of IBDs but also in many other inflammatory disorders.

Immunomodulatory and Immunosuppressive Roles of 1α,25(OH)2D3 in Autoimmune Diseases.

Autoimmune diseases are pathological conditions characterized by abnormal responses, accompanied by autoantibodies to self-molecules. The role of vitamin D in autoimmune diseases has increased significantly in the recent past from its functions in calcium and phosphate homoeostasis, and it is now involved in the regulations and proliferations of Th1 and Th17 lymphocyte. 1α,25(OH)2D3 is very important in ameliorations of inflammatory disorders arising from autoimmune diseases, but the mechanism by which this is performed is still a bone of contentions. This review aimed to highlight the existing facts about the roles of Vitamin D in the treatment and management of autoimmune diseases. An extensive online literature search was conducted using PubMed, MEDLINE and Scopus. Accumulated bodies of research evidence are available which demonstrates that Vitamin D has a very important part to play in the regulation of immune responses in autoimmune diseases. Some of the authors suggested that Vitamin D3 carry-out its immunosuppressive and immune modulatory action, through its actions on antigen-presenting cells and activated T and B cells with the help of Vitamin D receptors present on the each of these cells. Vitamin D supplementation assists in autoimmune disorders by making qualitative and quantitative changes in the immune system (downregulation of Th1 and upregulations of Th2 cells). This resulted in the body to be more tolerant of self and less likely to mount autoimmune responses.

Beneficial effects of omega-3 and vitamin E coadministration on gene expression of SIRT1 and PGC1α and serum antioxidant enzymes in patients with coronary artery disease.

BACKGROUND AND AIM: SIRT1 and PGC1α are two important genes, which play critical roles in regulating oxidative stress and inflammation processes. The study aimed assess the effects of coadministration of omega-3 and vitamin E supplements on SIRT1 and PGC1α gene expression and serum levels of antioxidant enzymes in coronary artery disease (CAD) patients. METHODS AND RESULTS: Participants of this randomized controlled trial included 60 CAD male patients who were categorized into three groups: Group 1 received omega-3 (4 g/day) and vitamin E placebo (OP), group 2 omega-3 (4 g/day) and vitamin E (400 IU/day; OE), and group 3 omega-3 and vitamin E placebos (PP) for 2 months. Gene expression of SIRT1 and PGC1α in peripheral blood mononuclear cells (PBMCS) was assessed by reverse transcription polymerase chain reaction (RT-PCR). Furthermore, serum antioxidant enzyme and high-sensitivity C-reactive protein (hsCRP) levels were assessed at the beginning and end of the intervention. Gene expression of SIRT1 and PGC1α increased significantly in the OE group (P = 0.039 and P = 0.050, respectively). Catalase and hsCRP levels increased significantly in the OE and OP groups. However, glutathione peroxidase (GPX) and superoxide dismutase (SOD) levels did not statistically change in all groups. The total antioxidant capacity (TAC) increased significantly in the OE group (P = 0.009) but not in OP and PP groups. CONCLUSION: Supplementation of omega-3 fatty acids in combination with vitamin E may have beneficial effects on CAD patients by increasing gene expression of SIRT1 and PGC1α and improving oxidative stress and inflammation in these patients.

Vitamin A supplementation reduces IL-17 and RORc gene expression in atherosclerotic patients.

Vitamin A is a potential mediator of T helper cells in atherosclerosis. The purpose of this study was to evaluate the effect of vitamin A supplementation on expression of Th17 cells-related IL-17 and RORc genes in atherosclerotic patients. Thirty one atherosclerotic patients and 15 healthy controls were studied for 4 months. Atherosclerotic patients were randomly divided into vitamin A or placebo groups. Healthy controls and patients in vitamin A group received 25,000 IU retinyl palmitate per day. Peripheral blood mononuclear cells were isolated, cultured and divided into three groups including fresh cells, phytohemagglutinin (PHA)-activated T cells and ox-LDL-activated T cells. Gene expressions of T cells were studied by real-time PCR. In atherosclerotic patients, vitamin A supplementation resulted in significant decrease in IL-17 gene expression by 0.63-fold in fresh cell, 0.82-fold in PHA-activated cells and 0.65-fold in ox-LDL-activated cells (P < 0.05 for all). RORc gene expression in fresh cells as well as ox-LDL-activated cells decreased significantly after vitamin A supplementation in atherosclerotic patients (P = 0.0001 for both). In PHA-activated cells, vitamin A supplementation significantly decreased RORc gene in both atherosclerotic patients and healthy subjects by 0.87-fold and 0.72, respectively, while in placebo group, the RORc gene expression significantly increased by 1.17-fold (P < 0.05 for all). Findings of this study suggest that vitamin A supplementation may be an effective approach to slow progression of atherosclerosis.

Insulin resistance via modification of PGC1α function identifying a possible preventive role of vitamin D analogues in chronic inflammatory state of obesity. A double blind clinical trial study.

AIM: Obesity-induced chronic inflammation is a key component of the pathogenesis of insulin resistance. Mounting evidence has demonstrated anti-inflammatory characteristics for vitamin D. Although analogues of vitamin D3 have extensively been used in the treatment of various chronic inflammatory diseases, to our knowledge, no such research is conducted in regards with obesity. The aim of this double blind clinical trial study is to investigate whether alphacalcidol treatment in obese subjects can affect the cytokine profile and insulin resistance. Moreover, we evaluated the pathways of vitamin D receptor (VDR), PPARγ and PGC1α gene expressions which may lead to insulin resistance following treatment with either alphacalcidol or placebo. METHODS: A total of 94 obese participants (BMI≥30) were recruited for the current double blind clinical trial study. Patients were divided into two intervention (N.=40) and control groups (N.=54) based on the stratified randomized method. One-Alpha® Capsules 1 microgram: alfacalcidol (1-α hydroxyvitamin D3) and placebo were given to subjects once a day for 8 weeks. Analysis of body composition was performed with use of Body Composition Analyzer. The circulating levels of TNF-α, IL-1ß, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, and 25-Hydroxy Vi-tamin D were measured with the use of EIA method. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. The real-time PCR using specific primer pairs for VDR, PGC1α, PPARγ, and ß-actin was performed. RESULTS: The FPG, fat percent and PTH levels were decreased and the levels of HDL-cholesterol and 25-hydroxy vitamin D were significantly increased after treatment with Alfacalcidol. Regarding to cytokines levels, the levels of IL6 were significantly decreased and IL10 were significantly increased in Alfacalcidol group in comparison with the control group. The relative expressions of VDR, PGC1α, and PPARγ genes significantly increased in Alfacalcidol group. We found also significant positive correlation between circulating 25-OH vitamin D and relative PGC1α gene expression in participants with insulin resistance. CONCLUSION: It seems that Alfacalcidol treatment may be effective in amelioration of the inflammatory state in obesity. This supplement might also improve resistance to insulin through enhancement of relative VDR and its downstream genes expression, which are demonstrated to be involved in glucose homeostasis pathways.

Impact of body mass index versus physical activity and calorie intake on assisted reproduction outcomes.

OBJECTIVE: To measure the effect of body mass index (BMI) versus calorie intake and physical activity (PA) on the outcomes of assisted reproductive technologies (ART). STUDY DESIGN: A prospective study was performed on 236 infertile women who underwent in vitro fertilization. BMI, level of PA and calorie intake were assessed at study entry, and associations between these variables and ART outcomes were analyzed. Participants were divided into four groups based on BMI and PA: normal BMI/inactive, normal BMI/active, overweight/inactive and overweight/active. RESULTS: BMI, adjusted for age, level of PA, calorie intake and aetiology of infertility, was not associated with the number of oocytes retrieved, fertilization rate, cleavage rate, number of embryos, number of high-quality embryos or pregnancy rate. For women aged <36 years, the number of oocytes retrieved and the number of embryos decreased with increasing BMI, independent of calorie intake and PA. The fertilization rate, cleavage rate, number of high-quality embryos and pregnancy rate were not associated with BMI. The number of oocytes retrieved was significantly higher in women of normal weight compared with overweight women, regardless of the level of PA. CONCLUSIONS: Age has a strong negative effect on ART parameters. Increased BMI, independent of calorie intake and PA, has an adverse effect on the number of oocytes retrieved in women aged <36 years, but does not affect the number of high-quality embryos or the success of the treatment cycle.

Vitamin D status and the predictors of circulating T helper 1-type immunoglobulin levels in Iranian subjects with type 1 diabetes and their siblings: a case-control study.

BACKGROUND: Vitamin D status has been linked to both T helper (Th)1/Th2 balance and susceptibility to type 1 diabetes (T1D). The present study aimed to evaluate vitamin D status and its relation to Th1/Th2 balance in subjects with T1D, their siblings and unrelated healthy controls during autumn and winter 2008-2009. METHODS: A case-control study was conducted on subjects with T1D (n(1) = 60) and two control groups comprising nondiabetic siblings (n(2) = 60) and unrelated healthy controls (n(3) = 60). Assessments of dietary intake, anthropometry, intact parathyroid hormone (iPTH) and 25(OH)D were performed. Serum levels of immunoglobulin (Ig)G(2) and IgE, as well as the IgG2/IgE ratio, were used to evaluate Th1/Th2 balance. Vitamin D status was defined based on circulating 25(OH)D as deficiency: <27.5 nm; insufficiency 27.5 ≤ 25(OH)D <50 nm; and sufficiency ≥50 nm. RESULTS: Vitamin D status did not differ significantly among the groups. Similarly, no significant difference in 25(OH)D, iPTH, IgG(2), IgE and IgG(2)/IgE was found. In multiple regression analysis of pooled data, PTH and body mass index were the predictors of IgG(2)/IgE. In the diabetic group, both PTH and age and, in siblings, PTH only, were the predictors of IgG(2)/IgE ratio. CONCLUSIONS: These data suggest PTH as the major predictor of immune deviance towards the Th1 response in both type 1 diabetic subjects and their siblings. Considering that the active form of vitamin D suppresses PTH production, it is hypothesised that vitamin D replenishment of just those who are genetically prone to the disease (i.e. siblings) may be regarded as a preventive measure against T1D.

Glasgow coma scale and its components on admission: are they valuable prognostic tools in acute mixed drug poisoning?

Introduction. The verbal, eye, and motor components of Glasgow coma scale (GCS) may be influenced by poisoned patients' behavior in an attempted suicide. So, the values of admission GCS and its components for outcomes prediction in mixed drugs poisoning were investigated. Materials and Methods. A followup study data was performed on patients with mixed drugs poisoning. Outcomes were recorded as without complications and with complications. Discrimination was evaluated by calculating the area under the receiver operating characteristic curves (AUC). Results. There was a significant difference between the mean value of each component of GCS as well as the total GCS between patients with and without complication. Discrimination was best for GCS (AUC: 0.933 ± 0.020) and verbal (0.932 ± 0.021), followed by motor (0.911 ± 0.025), then eye (0.89 ± 0.028). Conclusions. Admission GCS and its components seem to be valuable in outcome prediction of patients with mixed drug poisoning.

Fatality in paraquat poisoning.

INTRODUCTION: Acute paraquat (PQ) poisoning continues to be a major public health concern in many developing countries. This study was designed to evaluate the data on cases of acute PQ poisoning and compare the different variables between survivors and non-survivors. METHODS: All patients of PQ poisoning who were admitted to the poisoning emergency department during the past five years were retrospectively evaluated. The different variables that were compared between survivors and non-survivors included age and gender, the time from ingestion of PQ to hospital admission, the amount of PQ ingested, occurrence of vomiting after ingestion, the time from hospital admission to initiation of haemodialysis, the length of hospital stay and the outcomes. RESULTS: A total of 29 patients were evaluated. The in-hospital fatality rate was 55.2 percent. No significant differences were observed between survivors and non-survivors with regard to the patient characteristics. Most of the patients who died had ingested more than 40 mg/kg of 20 percent PQ (62.5 percent). There was a correlation between the outcome of patients and vomiting (p-value is 0.05; correlation coefficient is 0.45) and age (p-value is 0.013; correlation coefficient is 0.56). CONCLUSION: A large amount of ingested PQ, vomiting and age may be important variables to consider in association with the high fatality rate of PQ poisoning.

Identification of cross-reactive and restricted epitopes localized on human chorionic gonadotropin beta-subunit by monoclonal antibodies.

Human chorionic gonadotropin (hCG) belongs to the family of glycoprotein hormones. All members of the family are composed of an identical alpha subunit and structurally related beta subunit which confers biological specificity. Specific quantification and functional analysis of hCG require the use of monoclonal antibodies recognizing different epitopes of hCGbeta. This study describes the production and characterization of monoclonal antibodies (MAbs) to hCGbeta with no cross-reactivity to other glycoprotein hormones. Spleen cells from Balb/c mice immunized with hCG were fused with mouse SP2/0 myeloma cells. Fused cells were grown in hypoxanthine, aminopterine, and thymidine (HAT) selective medium and cloned by limiting dilution assay. Antibody-secreting cells were screened by enzyme-linked immunosorbent assay (ELISA) and the specificity of secreted MAbs was further analyzed, using a panel of highly purified and recombinant glycoprotein hormones, their subunits and peptides representing the C-terminal end of hCGbeta (hCGbeta-CTP) by ELISA and immunoblotting. The affinity constant (K(aff)) was also determined by ELISA. Three murine hybridomas designated G5M1, B12M2 and F4M3 were obtained that secrete MAbs specific for hCGbeta. The G5M1 MAb reacts only with hCGbeta, hCGbeta-CTP and intact hCG with no detectable cross-reaction with hCGalpha or any of the other glycoprotein hormones. The specificity of B12M2 MAb is very similar to G5M1, but it does not react with hCGbeta-CTP. The F4M3 MAb also has similar specificity to G5M1 and B12M2, but it strongly cross-reacts with hLH. The affinity constant (Kaff) of G5M1, B12M2 and F4M3 was found to be 4.28 x 10(9), 5.2 x 10(8), and 1.97 x 10(9) M(-1), respectively. Our results indicate that G5M1 and B12M2 MAbs are specific for hCG and recognize epitopes restricted to hCGbeta, but F4M3 recognizes a common epitope expressed both on hCGbeta and hLHbeta.