Oral drugs in multiple sclerosis therapy: An overview and a critical appraisal

Multiple sclerosis (MS) is characterized by demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of MS resulted in the introduction of numerous effective drugs with diverse mechanisms of actions, routes of administration and benefitrisk profiles. New oral drugs recently approved for MS treatment has led to significant achievements in MS management. The oral route of administration promotes patient satisfaction and increases therapeutic compliance; but their introduction has raised concerns regarding safety and tolerability; and a thorough analysis of the benefit/risk ratio is required. This article reviews the mechanisms of action, safety and efficacy of the licensed and experimental oral drugs in MS. Moreover, we put into perspective the disease, drug and patient-related factors that should be taken into account when considering the appropriate oral drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS

Prevalence and Incidence of Multiple Sclerosis in the City of Biancavilla

It is common that the epidemiology of multiple sclerosis (MS) varies with geography and ethnicity. Recent studies show a continuous growth of incidence and prevalence in Sicily, despite the controversial "latitude gradient theory.

Association of Systemic Inflammation Index and Body Mass Index with Survival in Patients with Renal Cell Cancer Treated with Nivolumab

Inflammation indexes and body mass index (BMI) are easily evaluated, predict survival, and are potentially modifiable. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of patients with renal cell carcinoma (RCC) undergoing immune checkpoint inhibitor therapy

Exposure to Endocrine Disrupters and Nuclear Receptor Gene Expression in Infertile and Fertile Women from Different Italian Areas

Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERa, ERb, AR, AhR, PPARg, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARg. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health

The influence of endocrine disruptors in a selected population of infertile women

Several studies report that endocrine disrupting chemicals (EDC) able to interfere with endocrine homeostasis may affect women's reproductive health. We analyzed EDC serum levels and nuclear receptors (NRs) expression in order to have an indication of the internal dose of biologically active compounds and a measurement of indicators of their effects, as a result of the repeated uptake from environmental source. The percentage of patients with detectable bisphenol A (BPA) concentrations was significantly higher in the infertile patients compared with fertile subjects. No significant difference was found between the groups with regard to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), mono-ethylhexyl phthalate (MEHP) and di-(2-ethylhexyl) phthalate (DEHP) concentrations. Among infertile women, the mean expression of estrogen receptor alpha (ERα) and beta (Erβ), androgen receptor (AR) and pregnane X receptor (PXR) was significantly higher than fertile patients. The mean expression of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPARγ) did not show significant differences between two groups. Patients with endometriosis had higher levels of PPARγ than all women with other causes of infertility. This study led further support to EDC exposure as a risk factor for women's fertility. © 2013 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Correlation of Endocrine Disrupting Chemicals Serum Levels and White Blood Cells Gene Expression of Nuclear Receptors in a Population of Infertile Women

Significant evidence supports that many endocrine disrupting chemicals could affect female reproductive health. Aim of this study was to compare the internal exposure to bisphenol A (BPA), perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), monoethylhexyl phthalate (MEHP), and di(2-ethylhexyl) phthalate (DEHP) in serum samples of 111 infertile women and 44 fertile women. Levels of gene expression of nuclear receptors (ER alpha, ER beta, AR, AhR, PXR, and PPAR gamma) were also analyzed as biomarkers of effective dose. The percentage of women with BPA concentrations above the limit of detection was significantly higher in infertile women than in controls. No statistically significant difference was found with regard to PFOS, PFOA, MEHP and DEHP. Infertile patients showed gene expression levels of ER alpha, ER beta, AR, and PXR significantly higher than controls. In infertile women, a positive association was found between BPA and MEHP levels and ER alpha, ER beta, AR, AhR, and PXR expression. PFOS concentration positively correlated with AR and PXR expression. PFOA levels negatively correlated with AhR expression. No correlation was found between DEHP levels and all evaluated nuclear receptors. This study underlines the need to provide special attention to substances that are still widely present in the environment and to integrate exposure measurements with relevant indicators of biological effects

Correlation of endocrine-disrupting chemicals serum levels and white blood cells gene expression of nuclear receptors in a population of infertile women

Significant evidence supports that many endocrine disrupting chemicals could affect female reproductive health. Aim of this study was to compare the internal exposure to bisphenol A (BPA), perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), monoethylhexyl phthalate (MEHP), and di(2-ethylhexyl) phthalate (DEHP) in serum samples of 111 infertile women and 44 fertile women. Levels of gene expression of nuclear receptors (ER α , ER β , AR, AhR, PXR, and PPAR γ ) were also analyzed as biomarkers of effective dose. The percentage of women with BPA concentrations above the limit of detection was significantly higher in infertile women than in controls. No statistically significant difference was found with regard to PFOS, PFOA, MEHP and DEHP. Infertile patients showed gene expression levels of ER α , ER β , AR, and PXR significantly higher than controls. In infertile women, a positive association was found between BPA and MEHP levels and ER α , ER β , AR, AhR, and PXR expression. PFOS concentration positively correlated with AR and PXR expression. PFOA levels negatively correlated with AhR expression. No correlation was found between DEHP levels and all evaluated nuclear receptors. This study underlines the need to provide special attention to substances that are still widely present in the environment and to integrate exposure measurements with relevant indicators of biological effect