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. Male Sprague-Dawley rats were injected intravenously with 0.3, 1 or 10 mg/kg body weight (bw) of praseodynium chloride (PrCl3), cerium chloride (CeCl3), neodymium chloride (NdCl3) and yttrium chloride (YCl3) administered together as a mixture. Serial blood samples were withdrawn up to 72 h following injection, and urine and feces were collected at predefined time intervals up to 7 days post-dosing. The REEs were measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). For a given REE dose, the time courses in blood, urine and feces were similar for all four REEs. However, the REE dose administered significantly impacted their kinetics, as lower cumulative excretion in urine and feces was associated with higher REE doses. The fraction of REE remaining in rat tissues at the terminal necropsy on post-dosing day 7 also increased with the dose administered, most notably in the lungs and spleen at the 10 mg/kg bw dose. The toxicokinetic parameters calculated from the blood concentration-time profiles further showed significant increases in the mean residence time (MRTIV) for all four REEs at the 10 mg/kg bw dose. The shift in the REE kinetics at high dose may be explained by a higher retention in lysosomes, the main organelle responsible for accumulation of these REEs in different tissues.

Biouptake of a rare earth metal (Nd) by Chlamydomonas reinhardtii - Bioavailability of small organic complexes and role of hardness ions.

A green alga, Chlamydomonas reinhardtii, was used to verify whether a simple Biotic Ligand Model (BLM) could be used to predict carefully controlled short-term biouptake for the lanthanide, Nd. In the absence of ligands or competitors, Nd biouptake was well described by a Michaelis-Menten equation with an affinity constant, KNd, of 106.8 M-1 and a maximum internalization flux of Jmax = 1.70 × 10-14 mol cm-2 s-1. For bi-metal mixtures containing Nd and Ca, Mg, Sm or Eu, Nd uptake could also be well modelled by assigning experimentally determined affinity constants of KCa = 102.6 M-1, KMg = 103.4 M-1, KSm = 106.5 M-1 and KEu = 106.5 M-1. The similar values of Km and Jmax for the three rare earth elements (REEs): Sm, Eu and Nd is consistent with them sharing a common metal uptake site. On the other hand, in the presence of the small organic ligands (citric or malic acid), neither, free or total Nd concentrations could be used to quantitatively predict Nd internalization fluxes. In other words, in order to predict biouptake by simple BLM determinations, it was necessary to consider that the Nd complexes were bioavailable. The data strongly suggest that risk evaluations of the REE will require a new paradigm and new tools for evaluating bioavailability.

The degradation and transport mechanism of a Mg-Nd-Zn-Zr stent in rabbit common carotid artery: A 20-month study.

Mg-based stent is a promising candidate of the next generation fully degradable vascular stents. The latest progress includes the CE approval of the Magmaris ® WE43 based drug eluting stent. However, so far, the long term (more than 1 year implantation) in vivo degradation and the physiological effects caused by the degradation products were still unclear. In this study, a 20 month observation was carried out after the bare Mg-Nd-Zn-Zr (abbr. JDBM) stent prototype was implanted into the common carotid artery of New Zealand white rabbit in order to evaluate its safety, efficacy and especially degradation behavior. The degradation of the main second phase Mg12Nd was also studied. Results showed that the bare JDBM stent had good safety and efficacy with a complete re-endothelialization within 28 days. The JDBM stent struts were mostly replaced in situ by degradation products in 4 month. The important finding was that the volume and Ca concentration of the degradation products decreased in the long term, eliminating the clinicians' concern of possible vessel calcification. In addition, the alloying elements Mg and Zn in the stent could be safely metabolized as continuous enrichment in any of the main organs were not detected although Nd and Zr showed an abrupt increase in spleen and liver after 1 month implantation. Collectively, the long term in vivo results showed the rapid re-endothelialization of JDBM stent and the long term safety of the degradation products, indicating its great potential as the backbone of the fully degradable vascular stent. STATEMENT OF SIGNIFICANCE: Mg-based stent is a promising candidate of the next generation fully degradable stents, especially after the recent market launch of one of its kind (Magmaris). However the fundamental question about the long term degradation and metabolic mechanism of Mg-based stent and its degradation products remain unanswered. We implanted our patented Mg-Nd-Zn-Zr bare stent into the common carotid artery of rabbits and conducted a 20 months observation. We found that the Ca containing degradation products could be further degraded in vivo. All the alloying elements showed no continuous enrichment in the main organs of rabbits. These findings eliminate the clinicians' concern of possible vessel calcification and element enrichment after the implantation of Mg alloy based stents to some extent.

Kinetics-mediate fabrication of multi-model bioimaging lanthanide nanoplates with controllable surface roughness for blood brain barrier transportation.

Effective delivery of imaging agents or therapeutics to the brain has remained elusive due to the poor blood-brain barrier (BBB) permeability, resulting in the apparent risks of inefficient diagnosis and therapeutic agents for brain disease. Herein, we report on the surface roughness mediated BBB transportation for the first time. The lanthanide-based core/shell/shell structured NaYF4:Yb,Er@NaGdF4:Yb@NaNdF4:Yb nanoplates with controllable surface roughness and multi-model bioimaging features were synthesized and used to evaluate the surface roughness dependent BBB permeability without any surface bio-functionalization. By controlling the kinetics of the shell coating process, the hexagon-disc, multi-petals and six-petals nanoplates with different surface roughness can be obtained. Comparing with the NPs with less Ra and receptor-conjugated NPs, the obtained six-petals nanoplates with highest roughness exhibit excellent performance in BBB transportation and tumor targeting, which lay solid foundation for the diagnosis and the therapy of brain tumor.

Assessment of optical path length in tissue using neodymium and water absorptions for application to near-infrared spectroscopy.

Quantitative analysis of blood oxygen saturation using near-IR spectroscopy is made difficult by uncertainties in both the absolute value and the wavelength dependence of the optical path length. We introduce a novel means of assessing the wavelength dependence of path length, exploiting the relative intensities of several absorptions exhibited by an exogenous contrast agent (neodymium). Combined with a previously described method that exploits endogenous water absorptions, the described technique estimates the absolute path length at several wavelengths throughout the visible/near-IR range of interest. Isolated rat hearts (n = 11) are perfused separately with Krebs-Henseleit buffer (KHB) and a KHB solution to which neodymium had been added, and visible/near-IR spectra are acquired using an optical probe made up of emission and collection fibers in concentric rings of diameters 1 and 3 mm, respectively. Relative optical path lengths at 520, 580, 679, 740, 800, 870, and 975 nm are 0.41+/-0.13, 0.49+/-0.21, 0.90+/-0.09, 0.94+/-0.01, 1.00, 0.84+/-0.01, and 0.78+/-0.08, respectively. The absolute path length at 975 nm is estimated to be 3.8+/-0.6 mm, based on the intensity of the water absorptions and the known tissue water concentration. These results are strictly valid only for the experimental geometry applied here.

[Effect of phosphate on the exchangeable form and the bioavailability of exogenous neodymium in soil].

Effects of phosphate on the exchangeable form and the bioavailability of exogenous neodymium (Nd) in soil were studied with 147Nd isotopic tracer. Exchangeable Nd was extracted with solution (pH8.2) of NaAc. The results indicated that Nd beyond 99.5% was adsorbed by soil whether phosphate exists in soil or not. Phosphate can precipitate dramatically Nd3+. And the Nd phosphate precipitates may set limits on the concentration of exchangeable Nd observed in soil. KH2PO4 ranging from 0.3 g.kg-1 to 1.5 g.kg-1 make a uniform impact on the exchangeable form of Nd. In addition, phosphate in soil can inhibit wheat seedling to absorb Nd. The concentration of exchangeable Nd is correlated significantly with the content of Nd in wheat seedling.

Studies on the incorporation of lanthanides in dental hard tissues.

Rare earth elements (lanthanides)--known from chrystal-chemistry for the rehardening effect on apatites--have been tested previously for the possibility of their incorporation in dental enamel. From the non-toxic lanthanides cerium was incorporated under in vitro conditions in human dental enamel. In the present study, the incorporation of lanthanum (La), europium (Eu), samarium (Sa), ytterbium (Yb) and neodymium (Nd) in human permanent enamel, dentine and deciduous enamel has been investigated by neutron activation analysis. The lanthanides were incorporated--following the above sequence--in an increasing ratio into enamel and dentine, by forming new, more resistant rare earth elements containing apatite structures.