Toxicokinetics of rare earth element oxides administered intravenously to rats.

Rare earth elements (REEs) are increasingly used in a wide range of applications. However, their toxicokinetic behaviors in animals and humans are not yet fully documented, hindering health risk assessments. We used a rat experimental model to provide novel data on the toxicokinetics of the insoluble oxide forms of praseodymium (Pr), neodymium (Nd), cerium (Ce) and yttrium (Y) administered intravenously.

Toxicokinetics of praseodymium and cerium administered as chloride salts in Sprague-Dawley rats: impacts of the dose and of co-exposure with additional rare earth elements.

We conducted a rat exposure study to assess the impacts of dose and co-exposure with other rare earth elements (REEs) on the toxicokinetics of praseodymium (Pr) and cerium (Ce). We first determined the kinetic profiles of elemental Pr and Ce in blood, urine and feces along with tissue levels at sacrifice on the seventh day following intravenous injection of PrCl or CeCl at 0.3 or 1 mg/kg bw (of the chloride salts) in adult male Sprague-Dawley rats (n = 5 per group).

A bioinformatics framework for targeted gene expression assay design: Application to in vitro developmental neurotoxicity screening in a rat model.

Brain development involves a series of intricately choreographed neuronal differentiation and maturation steps that are acutely vulnerable to interferences from chemical exposures. Many genes involved in neurodevelopmental processes show evolutionarily conserved expression patterns in mammals and may constitute useful indicators/biomarkers for the evaluation of potential developmental neurotoxicity. Based on these premises, this study developed a bioinformatics framework to guide the design of a gene expression-based in vitro developmental neurotoxicity assay targeting evolutionary conserved genes associated with neuronal differentiation and maturation in rat cerebellar granule cells (CGCs).

Toxicokinetics in rats and modeling to support the interpretation of biomonitoring data for rare-earth elements.

Toxicokinetic models are useful tools to better understand the fate of contaminants in the human body and to establish biological guidance values to interpret biomonitoring data in human populations. This research aimed to develop a biologically-based toxicokinetic model for four rare earth elements (REEs), cerium (Ce), praseodymium (Pr), neodymium (Nd) and yttrium (Y), and to establish biomonitoring equivalents (BE) serving as biological guidance values. The model was constructed using physiological data taken from the literature as well as new experimental kinetic data.

Effect of the dose on the toxicokinetics of a quaternary mixture of rare earth elements administered to rats.

Large human biomonitoring studies are starting to assess exposure to rare earth elements (REEs). Yet, there is a paucity of data on the toxicokinetics of these substances to help interpret biomonitoring data. The objective of the study was to document the effect of the administered dose on the toxicokinetics of REEs.

Synthesis of Imidazo[1,2-]pyridines: Triflic Anhydride-Mediated Annulation of 2-Azirines with 2-Chloropyridines.

The discovery and optimization of a reaction between 2-chloropyridines and 2-azirines producing imidazo[1,2-]pyridines is described. The treatment of 2-azirines with triflic anhydride (TfO) forms an electrophilic 1-trifloyl-aziridin-2-yl triflate species which, when reacted with 2-halopyridines, generates transient pyridinium salts. These salts were treated in the same pot with triethylamine (EtN), leading to the selective formation of C3-substituted imidazo[1,2-]pyridines, an heterocyclic moiety commonly found in medicinal chemistry leads and drugs.

Characterization of the rat Acetylcholinesterase readthrough (AChE-R) splice variant: Implications for toxicological studies.

Exposure to chemicals and other environmental stressors can differentially impact the expression of Acetylcholinesterase (AChE) splice variants. Surprisingly, despite the widespread use of the rat model in toxicological studies and the wealth of literature on this important biomarker of neurotoxicity, AChE coding exons and splice variants are not yet fully annotated in this species. To address this knowledge gap, a short problematic region of the rat AChE genomic DNA present in GenBank was first re-sequenced.

A bioinformatics workflow for the evaluation of RT-qPCR primer specificity: Application for the assessment of gene expression data reliability in toxicological studies.

The reliability of Reverse Transcription quantitative real-time PCR (RT-qPCR) gene expression data depends on proper primer design and RNA quality controls. Despite freely available genomic databases and bioinformatics tools, primer design deficiencies can be found across life science publications. In order to assess the prevalence of such deficiencies in the toxicological literature, 504 primer sets extracted from a random selection of 70 recent rat toxicological studies were evaluated.

Comparison of tris(2-ethylhexyl) phosphate and di(2-ethylhexyl) phosphoric acid toxicities in a rat 28-day oral exposure study.

Tris(2-ethylhexyl) phosphate (TEHP, CAS no. 78-42-2) is a plasticizer and a flame retardant, while di(2-ethylhexyl) phosphoric acid (DEHPA, CAS no. 298-07-7) is an oil additive and extraction solvent.

Associations between air pollution and cardio-respiratory physiological measures in older adults exercising outdoors.

We examined whether exercising indoors vs. outdoors reduced the cardio-respiratory effects of outdoor air pollution. Adults ≥55 were randomly assigned to exercise indoors when the Air Quality Health Index was ≥5 and outdoors on other days (intervention group, n = 37), or outdoors everyday (control group, n = 35).

Co-administration of a Rhododendron tomentosum extract does not affect mercury tissue concentrations and excretion rate in methylmercury-treated adult male rats.

Objectives: Consumption of fish/seafood is clearly linked to higher mercury levels in human tissue samples. However, correlations between methylmercury (MeHg) intakes calculated from dietary surveys and mercury body burdens are usually weak and can vary across populations. Different factors may affect MeHg absorption, distribution, metabolism and excretion, including co-exposures to phytochemicals and antibiotics, which were shown to affect mercury body burdens in rodents.

Metals and oxidative potential in urban particulate matter influence systemic inflammatory and neural biomarkers: A controlled exposure study.

Background: Oxidative stress and inflammation are considered to be important pathways leading to particulate matter (PM)-associated disease. In this exploratory study, we examined the effects of metals and oxidative potential (OP) in urban PM on biomarkers of systemic inflammation, oxidative stress and neural function.

Methods: Fifty-three healthy non-smoking volunteers (mean age 28 years, twenty-eight females) were exposed to coarse (2.

A PCR-based quantitative assay for the evaluation of mRNA integrity in rat samples.

Reverse Transcription quantitative real-time PCR (RT-qPCR) is applied to quantify gene transcript levels in a wide range of investigations. Proper assessment of RNA integrity is essential for reliable assessment of gene expression levels, as RNA molecules are acutely vulnerable to degradation. However, RNA quality control measures are still infrequently reported in rat toxicological studies, which impede proper evaluation of gene expression data reliability.

Rapid phenolic O-glycosylation of small molecules and complex unprotected peptides in aqueous solvent.

Glycosylated natural products and synthetic glycopeptides represent a significant and growing source of biochemical probes and therapeutic agents. However, methods that enable the aqueous glycosylation of endogenous amino acid functionality in peptides without the use of protecting groups are scarce. Here, we report a transformation that facilitates the efficient aqueous O-glycosylation of phenolic functionality in a wide range of small molecules, unprotected tyrosine, and tyrosine residues embedded within a range of complex, fully unprotected peptides.

Measurement of Mitochondrial Oxygen Consumption in Permeabilized Fibers of Drosophila Using Minimal Amounts of Tissue.

The fruit fly, Drosophila melanogaster, represents an emerging model for the study of metabolism. Indeed, drosophila have structures homologous to human organs, possess highly conserved metabolic pathways and have a relatively short lifespan that allows the study of different fundamental mechanisms in a short period of time. It is, however, surprising that one of the mechanisms essential for cellular metabolism, the mitochondrial respiration, has not been thoroughly investigated in this model.

Cardiorespiratory Effects of Air Pollution in a Panel Study of Winter Outdoor Physical Activity in Older Adults.

Objective: The aim of this study was to assess cardiorespiratory effects of air pollution in older adults exercising outdoors in winter.

Methods: Adults 55 years of age and older completed daily measurements of blood pressure, peak expiratory flow and oximetry, and weekly measurements of heart rate variability, endothelial function, spirometry, fraction of exhaled nitric oxide and urinary oxidative stress markers, before and after outdoor exercise, for 10 weeks. Data were analyzed using linear mixed effect models.

Cardio-Respiratory Effects of Air Pollution in a Panel Study of Outdoor Physical Activity and Health in Rural Older Adults.

Objective: To examine cardio-respiratory effects of air pollution in rural older adults exercising outdoors.

Methods: Adults 55 and over completed measurements of blood pressure, peak expiratory flow and oximetry daily, and of heart rate variability, endothelial function, spirometry, fraction of exhaled nitric oxide and urinary oxidative stress markers weekly, before and after outdoor exercise, for 10 weeks. Data were analyzed using linear mixed effect models.

General C-H Arylation Strategy for the Synthesis of Tunable Visible Light-Emitting Benzo[a]imidazo[2,1,5-c,d]indolizine Fluorophores.

Herein we report the discovery of the benzo[a]imidazo[2,1,5-c,d]indolizine motif displaying tunable emission covering most of the visible spectrum. The polycyclic core is obtained from readily available amides via a chemoselective process involving TfO-mediated amide cyclodehydration, followed by intramolecular C-H arylation. Additionally, these fluorescent heterocycles are easily functionalized using electrophilic reagents, enabling divergent access to varied substitution.

Influence of exposure to coarse, fine and ultrafine urban particulate matter and their biological constituents on neural biomarkers in a randomized controlled crossover study.

Background: Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear.

Objectives: We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles.

Cytosolic Triosephosphate Isomerase from Is Reversibly Modified by Glutathione on Cysteines 127 and 218.

In plant cells, an increase in cellular oxidants can have multiple effects, including the promotion of mixed disulfide bonds between glutathione and some proteins (-glutathionylation). The present study focuses on the cytosolic isoform of the glycolytic enzyme triosephosphate isomerase (cTPI) from and its reversible modification by glutathione. We used purified recombinant cTPI to demonstrate the enzyme sensitivity to inhibition by -ethylmaleimide, hydrogen peroxide and diamide.

Associations between urinary biomarkers of oxidative stress and air pollutants observed in a randomized crossover exposure to steel mill emissions.

The effects of industrial air pollution on human health have not been as thoroughly investigated as those of urban air pollution which originates mostly from automotive transport. To better assess the health impacts of point sources of industrial air pollution, a randomized crossover exposure study was conducted. Sixty one young and healthy volunteers were randomly assigned to spend five consecutive eight-hour days near a steel mill or at a location five kilometres away.

Aqueous Glycosylation of Unprotected Sucrose Employing Glycosyl Fluorides in the Presence of Calcium Ion and Trimethylamine.

We report a synthetic glycosylation reaction between sucrosyl acceptors and glycosyl fluoride donors to yield the derived trisaccharides. This reaction proceeds at room temperature in an aqueous solvent mixture. Calcium salts and a tertiary amine base promote the reaction with high site-selectivity for either the 3'-position or 1'-position of the fructofuranoside unit.

A PCR-based approach to assess genomic DNA contamination in RNA: Application to rat RNA samples.

Genomic DNA (gDNA) contamination of RNA samples can lead to inaccurate measurement of gene expression by reverse transcription quantitative real-time PCR (RT-qPCR). We describe an easily adoptable PCR-based method where gDNA contamination in RNA samples is assessed by comparing the amplification of intronic and exonic sequences from a housekeeping gene. Although this alternative assay was developed for rat RNA samples, it could be easily adapted to other species.

Perinatal methylmercury exposure perturbs the expression of Plp1 and Cnp splice variants in cerebellum of rat pups.

Early life exposure to environmental chemicals can interfere with myelin formation in the developing brain, leading to neurological disorders. The Proteolipid Protein 1 (Plp1), Myelin Basic Protein (Mbp) and 2',3'-Cyclic Nucleotide 3'Phosphodiesterase (Cnp) genes expressed in oligodendrocytes and involved in myelination processes can be useful biomarkers of potential developmental neurotoxicity. In an earlier study, we concluded that the reduction in the expression levels of Mbp splice variants in juvenile rat cerebellum following perinatal methylmercury (MeHg) exposure were compatible with an overall reduction of mature oligodendrocytes population.

Cyclooxygenase 1 mRNA expression is undetectable in Madin Darby Canine Kidney cells.

Background: Madin Darby Canine Kidney (MDCK) cells form polarized epithelium in vitro and are routinely used in research fields ranging from protein trafficking to influenza. However, the canine origin of these cells also means that compared to man or mouse, genomic resources are more limited and performance of commercially available antibodies often untested. The synthesis of pro-inflammatory prostaglandins in the kidney is mediated by the constitutively expressed cyclooxygenase 1 and the inducible cyclooxygenase 2 (COX-1 and COX-2, respectively).