Guidance for establishing and applying tolerable upper intake levels for vitamins and essential minerals.

Vitamins and essential minerals are micronutrients that are required for the normal functioning of the human body. However, they may lead to adverse health effects if consumed in excess. A tolerable upper intake level (UL) is a science-based reference value that supports policy-makers and other relevant actors in managing the risks of excess nutrient intake.

Perfluoroalkyl substances and immunotoxicity: An in vitro structure-activity relationship study in THP-1-derived monocytes and macrophages.

Recently, PFASs toxicity for the human immune system has become a growing concern. However, there is currently limited information on PFASs immunotoxicity beyond PFHxS, PFOA, PFOS, and PFNA. Therefore, it is urgent to close the present knowledge gap by testing a wider range of compounds.

Scientific opinion on the tolerable upper intake level for vitamin E.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin E. As -tocopherol is recognised as the only essential form of vitamin E, the Panel restricted its evaluation to -tocopherol. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of vitamin E, namely risk of impaired coagulation and bleeding, cardiovascular disease and prostate cancer.

Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements.

Pre-workout supplements are popular among sport athletes and overweight individuals. Phenethylamines (PEAs) and alkylamines (AA) are widely present in these supplements. Although the health effects of these analogues are not well understood yet, they are hypothesised to be agonists of adrenergic (ADR) and trace amine-associated receptors (TAARs).

Determination of immunotoxic potencies of a series of perfluoralkylsubstances (PFASs) in human Namalwa B lymphocyte and human Jurkat T lymphocyte cells.

Exposure to PFASs is associated to several adverse health effects, such as immunotoxicity. Immunotoxic effects of PFOA and PFOS, including a reduced antibody response in both experimental animals and humans, have been reported. However, there is limited understanding of the underlying mechanisms involved.

Androgen Receptor and Cardiovascular Disease: A Potential Risk for the Abuse of Supplements Containing Selective Androgen Receptor Modulators.

The androgen receptor (AR) is a member of the family of ligand-activated transcription factors. Selective androgen receptor modulators (SARMs) exert their biological function through complex interactions with the AR. It has been speculated that overexertion of AR signaling cascades as a result of SARM abuse can be a risk factor for the development of various cardiovascular diseases.

Scientific opinion on the tolerable upper intake level for vitamin B6.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for vitamin B6. Systematic reviews of the literature were conducted by a contractor. The relationship between excess vitamin B6 intakes and the development of peripheral neuropathy is well established and is the critical effect on which the UL is based.

What Happened and Why: Responding to Racism, Discrimination, and Microaggressions in the Clinical Learning Environment.

Introduction: Within clinical learning environments, medical students are uniquely faced with power differentials that make acts of racism, discrimination, and microaggressions (RDM) challenging to address. Experiences of microaggressions and mistreatment are correlated with higher rates of positive depression screening and lower satisfaction with medical training. We developed a curriculum for medical students beginning clerkship rotations to promote the recognition of and response to RDM.

Mixture effects of tetrodotoxin (TTX) and drugs targeting voltage-gated sodium channels on spontaneous neuronal activity in vitro.

Tetrodotoxin (TTX) potently inhibits TTX-sensitive voltage-gated sodium (Na) channels in nerve and muscle cells, potentially resulting in depressed neurotransmission, paralysis and death from respiratory failure. Since a wide range of pharmaceutical drugs is known to also act on Na channels, the use of medicines could predispose individuals to a higher susceptibility towards TTX toxicity. We therefore first assessed the inhibitory effect of selected medicines that act on TTX-sensitive (Riluzole, Chloroquine, Fluoxetine, Valproic acid, Lamotrigine, Lidocaine) and TTX-resistant (Carbamazepine, Mexiletine, Flecainide) Na channels on spontaneous neuronal activity of rat primary cortical cultures grown on microelectrode arrays (MEA).

Investigating the cytotoxicity of per- and polyfluoroalkyl substances in HepG2 cells: A structure-activity relationship approach.

Per- and polyfluoroalkyl substances (PFAS) are a family of man-made chemicals with currently over 4'700 compounds identified. While toxicological data are available for some of the legacy PFAS, such as PFOA and PFOS, a knowledge gap remains concerning both emerging and legacy PFAS' toxicity due to the diversity of the PFAS. Therefore, a better understanding of the PFAS structure-activity relationship may prove helpful.

Current approaches and challenges of sample preparation procedures for the safety assessment of paper and cardboard food contact materials: A comprehensive review.

In the European Union (EU), Regulation (EC) 1935/2004 provides a harmonized legal EU framework and sets out the general principles for safety and inertness for all Food Contact Materials (FCMs) and Food Contact Articles. From a food safety point of view, however, specific EU legislation for paper and cardboard FCMs is lacking, while at Member State level, national legislation differs among countries. More than 11,000 chemicals have been identified in all types of FCMs, most of them without any information on toxicity or migration potential from FCM to food.

The impact of legacy and novel perfluoroalkyl substances on human cytochrome P450: An in vitro study on the inhibitory potential and underlying mechanisms.

Per- and polyfluoroalkyl substances (PFASs) are a group of synthetic compounds with a wide range of industrial applications. PFOA and PFOS have been the most extensively studied and have been associated with hepatotoxicity. Recently, the interaction with cytochrome P450 (CYP) has been proposed as a potential key molecular event leading to PFAS-induced hepatotoxicity.

Gastrointestinal digestion of dietary advanced glycation endproducts increases their pro-inflammatory potential.

Thermal treatment of food products leads to the formation of dietary advanced glycation endproducts (dAGEs). It was previously shown that dAGEs induce TNF-α secretion in human macrophage-like cells. To what extent gastrointestinal digestion of dAGEs influences these pro-inflammatory effects and what the implications of these pro-inflammatory characteristics further down the human gastrointestinal tract are, are currently unknown.

Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity.

Vitamin B-6 in the form of pyridoxine (PN) is commonly used by the general population. The use of PN-containing supplements has gained lots of attention over the past years as they have been related to the development of peripheral neuropathy. In light of this, the number of reported cases of adverse health effects due to the use of vitamin B-6 have increased.

Red yeast rice (Monascus purpureus) supplements: Case series assessment of spontaneously reported cases to The Netherlands Pharmacovigilance Centre Lareb.

Serious concerns are expressed on the safe use of red yeast rice (RYR) supplements. The aim of the present study was to analyse cases received by Lareb on RYR-related adverse health events. These cases were analysed for the number of reports, number of adverse drug reactions (ADRs), causality, seriousness of the reaction, latency-period, age and sex of the patients, concomitant medication and type of reporter.

Analysis and reflection on the role of the 90-day oral toxicity study in European chemical risk assessment.

The 90-day toxicity study is one of the studies used in the safety assessment of food ingredients, medicines or other chemical substances. This paper reviews the current role of the 90-day oral toxicity study in European regulatory dossiers of chemicals by reviewing EU legislation and EU and OECD guidance documents. Regulatory provisions with regard to necessity, objectives and design of such 90-day toxicity studies vary between the different sectors addressed in this review.

Dietary Advanced Glycation Endproducts and the Gastrointestinal Tract.

The prevalence of inflammatory bowel diseases (IBD) is increasing in the world. The introduction of the Western diet has been suggested as a potential explanation of increased prevalence. The Western diet includes highly processed food products, and often include thermal treatment.

Gastrointestinal digestion of dietary advanced glycation endproducts using an in vitro model of the gastrointestinal tract (TIM-1).

Protein- and sugar-rich food products processed at high temperatures contain large amounts of dietary advanced glycation endproducts (dAGEs). Our earlier studies have shown that specifically protein-bound dAGEs induce a pro-inflammatory reaction in human macrophage-like cells. To what extent these protein-bound dAGEs survive the human gastrointestinal (GI) tract is still unclear.

Role of antioxidants in the treatment of gastroesophageal reflux disease-associated idiopathic pulmonary fibrosis.

Purpose Of Review: Idiopathic pulmonary fibrosis (IPF) is a terminal lung disease of largely unknown cause. Gastroesophageal reflux disease (GERD) was recently discovered to be a trigger for the development of IPF. The current pharmaceutical approach to IPF falls short and there is a pressing need for improved therapeutic options.

Dietary Advanced Glycation Endproducts Decrease Glucocorticoid Sensitivity In Vitro.

Glucocorticoids are very effective anti-inflammatory drugs and widely used for inflammatory bowel disease (IBD) patients. However, approximately 20% of IBD patients do not respond to glucocorticoids and the reason for this is largely unknown. Dietary advanced glycation endproducts (AGEs) are formed via the Maillard reaction during the thermal processing of food products and can induce a pro-inflammatory reaction in human cells.

Haemodynamic effects of the flavonoid quercetin in rats revisited.

Background And Purpose: The flavonoid quercetin increased the in vitro potency of the α -antagonist tamsulosin to reduce phenylephrine-dependent arterial contractions by 10-fold. To examine if this supplement-drug interaction luxates hypotensive and orthostatic events in vivo, several set of studies were conducted in spontaneously hypertensive (SHR) and normotensive (Wistar Kyoto [WKY]) rats.

Experimental Approach: First, in rats pretreated with quercetin or its vehicle, responses to phenylephrine and tamsulosin were examined.

Dietary Advanced Glycation Endproducts Induce an Inflammatory Response in Human Macrophages in Vitro.

Advanced glycation endproducts (AGEs) can be found in protein- and sugar-rich food products processed at high temperatures, which make up a vast amount of the Western diet. The effect of AGE-rich food products on human health is not yet clear and controversy still exists due to possible contamination of samples with endotoxin and the use of endogenous formed AGEs. AGEs occur in food products, both as protein-bound and individual molecules.

Nanoparticle-based targeted cancer strategies for non-invasive prostate cancer intervention.

Prostate cancer is screened by testing circulating levels of the prostate-specific antigen (PSA) biomarker, monitoring changes over time, or a digital rectal exam. Abnormal results often lead to prostate biopsy. Prostate cancer positive patients are stratified into very low-risk, low-risk, intermediate-risk, and high-risk, based on clinical classification parameters, to assess therapy options.