High Zn content of Randall's plaque: A μ-X-ray fluorescence investigation

Kidney stone disease, or nephrolithiasis, is a common ailment. Among the different risk factors usually associated with nephrolithiasis are dehydration, metabolic defects (especially with regard to calcium and oxalate). The presence of a mineral deposit at the surface of the renal papilla (termed Randall's plaque) has all been recently underlined. Of note, Randall's plaque is made of the calcium phosphate, carbapatite, and serves as a nucleus for kidney stone formation. The process by which apatite nanocrystals nucleate and form Randall's plaque remains unclear. This paper deals with the possible relationship between trace elements and the formation of this mineral. The investigation has been performed on a set of Randall's plaques, extracted from human kidney stones, through μ-X-ray diffraction and μ-X-ray fluorescence analyses in order to determine the chemical composition of the plaque as well as the nature and the amount of trace elements. Our data provide evidence that Zn levels are dramatically increased in carbapatite of RP by comparison to carbapatite in kidney stones, suggesting that calcified deposits within the medullar interstitium are a pathological process involving a tissue reaction. Further studies, perhaps including the investigation of biomarkers for inflammation, are necessary for clarifying the role of Zn in Randall's plaque formation

Mineral studies in enamel, an exemplary model system at the interface between physics, chemistry and medical sciences

AbstractEnamel is an exemplary material for physicochemical analyses of biological mineral. Hereditary and environmental enamel defects as well as secondary decay processes induce degradation and destruction of enamel matter. This exceptional mineralized tissue is unable to regenerate due to the loss of the cell forming enamel: the ameloblasts. Deciphering mechanisms of enamel degradation represent a scientific challenge of economic interest. The interface between physics, chemistry, and biomedical science has been initiated for a long time. An updated review of a classical and routinely available set of different techniques is proposed to illustrate the interface between oral sciences and physico-chemistry. Research in this field has greatly evolved over the past decade thanks to various extremely sensitive techniques in Materials Science available for translational research in biomedicine

FAM20A Gene Mutation: Amelogenesis or Ectopic Mineralization?

Background and objective:FAM20A gene mutations result in enamel renal syndrome (ERS) associated with amelogenesis imperfecta (AI), nephrocalcinosis, gingival fibromatosis, and impaired tooth eruption. FAM20A would control the phosphorylation of enamel peptides and thus enamel mineralization. Here, we characterized the structure and chemical composition of unerupted tooth enamel from ERS patients and healthy subjects.Methods: Tooth sections were analyzed by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray Diffraction (XRD), and X-Ray Fluorescence (XRF).Results: SEM revealed that prisms were restricted to the inner-most enamel zones. The bulk of the mineralized matter covering the crown was formed by layers with varying electron-densities organized into lamellae and micronodules. Tissue porosity progressively increased at the periphery, ending with loose and unfused nanonodules also observed in the adjoining soft tissues. Thus, the enamel layer covering the dentin in all ERS patients (except a limited layer of enamel at the dentino-enamel junction) displayed an ultrastructural globular pattern similar to one observed in ectopic mineralization of soft tissue, notably in the gingiva of Fam20a knockout mice. XRD analysis confirmed the existence of alterations in crystallinity and composition (vs. sound enamel). XRF identified lower levels of calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount of calcium in ERS enamel, which appeared similar to dentin.Conclusion: This study suggests that, after an initial normal start to amelogenesis, the bulk of the tissue covering coronal dentin would be formed by different mechanisms based on nano- to micro-nodule aggregation. This evocated ectopic mineralization process is known to intervene in several soft tissues in FAM20A gene mutant

How to assess the role of Pt and Zn in the nephrotoxicity of Pt anti-cancer drugs?: An investigation combining μXRF and statistical analysis. Part II: Clinical application

International audienceIn this contribution, an approach developed previously for mice is used for human biopsy. In the case of patient 1, Pt detection is performed 6 days after the last oxaliplatin infusion, while for patient 2, the biopsy was performed more than 15 days after his first platin infusion and several dialysis. Even for these biological samples, experiments show that synchrotron mediated mXRF is a suitable tool to detect Pt in kidney biopsy, and thus probably for any organ exposed to Pt. Therefore, mXRF could also be of major interest to decipher the mechanism beyond Pt induced neurotoxicity, ototoxicity on human biopsy. Pharmacoavailability of chemotherapies is a major concern because some treatment failures are explained by poor tumor penetration of the active molecule. mXRF could be an elegant way to map the distribution of Pt inside cancerous cells at the micrometer scale. Pt and Zn are only two of the numerous trace elements that mXRF can detect; heavy metal intoxication diagnosis and the toxicity mechanism probably could also benefit from this innovative technique

Comparative Physicochemical Analysis of Pulp Stone and Dentin

International audienceIntroductionOdontoblasts are responsible for the synthesis of dentin throughout the life of the tooth. Tooth pulp tissue may undergo a pathologic process of mineralization, resulting in formation of pulp stones. Although the prevalence of pulp stones in dental caries is significant, their development and histopathology are poorly understood, and their precise composition has never been established. The aim of the present study was to investigate the physicochemical properties of the mineralized tissues of teeth to elucidate the pathologic origin of pulp stones.MethodsAreas of carious and healthy dentin of 8 decayed teeth intended for extraction were analyzed and compared. In addition, 6 pulp stones were recovered from 5 teeth requiring root canal treatment. The samples were embedded in resin, sectioned, and observed by scanning electron microscopy and energy-dispersive spectroscopy. X-ray diffraction was performed to identify phases and crystallinity. X-ray fluorescence provided information on the elemental composition of the samples.ResultsPulp stones showed heterogeneous structure and chemical composition. X-ray diffraction revealed partially carbonated apatite. X-ray fluorescence identified P, Ca, Cu, Zn, and Sr within dentin and pulp stones. Zn and Cu concentrations were higher in pulp stones and carious dentin compared with healthy dentin.ConclusionsPulpal cells produce unstructured apatitic mineralizations containing abnormally high Zn and Cu levels

De la simple hélice aux nanostructures tubulaires

Le même formalisme est utilisé pour expliquer la diffraction par l’ADN et par les nanotubes de carbone ou leurs analogues d’oxydes métalliques, les nanotubes d’imogolite. La diffraction permet à la fois de déterminer la structure et l’organisation des nanotubes. De la diffraction électronique à celle des rayons X, nous discutons des propriétés individuelles et d’ensemble de ces nanostructures

The status of strontium in biological apatites: an XANES/EXAFS investigation

International audienceOsteoporosis represents a major public health problem through its association with fragility fractures. The public health burden of osteoporotic fractures will rise in future generations, due in part to an increase in life expectancy. Strontium-based drugs have been shown to increase bone mass in postmenopausal osteoporosis patients and to reduce fracture risk but the molecular mechanisms of the action of these Sr-based drugs are not totally elucidated. The local environment of Sr(2+) cations in biological apatites present in pathological and physiological calcifications in patients without such Sr-based drugs has been assessed. In this investigation, X-ray absorption spectra have been collected for 17 pathological and physiological calcifications. These experimental data have been combined with a set of numerical simulations using the ab initio FEFF9 X-ray spectroscopy program which takes into account possible distortion and Ca/Sr substitution in the environment of the Sr(2+) cations. For selected samples, Fourier transforms of the EXAFS modulations have been performed. The complete set of experimental data collected on 17 samples indicates that there is no relationship between the nature of the calcification (physiological and pathological) and the adsorption mode of Sr(2+) cations (simple adsorption or insertion). Such structural considerations have medical implications. Pathological and physiological calcifications correspond to two very different preparation procedures but are associated with the same localization of Sr(2+) versus apatite crystals. Based on this study, it seems that for supplementation of Sr at low concentration, Sr(2+) cations will be localized into the apatite network

Combining μX-ray fluorescence, μXANES and μXRD to shed light on Zn2+ cations in cartilage and meniscus calcifications

International audienceWe aimed to examine the presence of Zn, a trace element, in osteoarthritis (OA) cartilage and meniscus from patients undergoing total knee joint replacement for primary OA. We mapped Ca2+ and Zn2+ at the mesoscopic scale by X-ray fluorescence microanalysis (μX-ray) to determine the spatial distribution of the 2 elements in cartilage, μX-ray absorption near edge structure spectroscopy to identify the Zn species, and μX-ray diffraction to determine the chemical nature of the calcification. Fourier transform infrared spectroscopy was used to determine the chemical composition of cartilage and meniscus. Ca2+ showed a heterogeneous spatial distribution corresponding to the calcifications within cartilage (or meniscus) or at their surface. At least 2 Zn2+ species were present: the first may correspond to Zn embedded in protein (different Zn metalloproteins are known to prevent calcification in biological tissues), and the second may be associated with a Zn trap in or at the surface of the calcification. Calcification present in OA cartilage may significantly modify the spatial distribution of Zn; part of the Zn may be trapped in the calcification and may alter the associated biological function of Zn metalloproteins

How to assess the role of Pt and Zn in the nephrotoxicity of Pt anti-cancer drugs?: An investigation combining mXRF and statistical analysis. Part II: Clinical application

International audienceIn this contribution, an approach developed previously for mice is used for human biopsy. In the case of patient 1, Pt detection is performed 6 days after the last oxaliplatin infusion, while for patient 2, the biopsy was performed more than 15 days after his first platin infusion and several dialysis. Even for these biological samples, experiments show that synchrotron mediated mXRF is a suitable tool to detect Pt in kidney biopsy, and thus probably for any organ exposed to Pt. Therefore, mXRF could also be of major interest to decipher the mechanism beyond Pt induced neurotoxicity, ototoxicity on human biopsy. Pharmacoavailability of chemotherapies is a major concern because some treatment failures are explained by poor tumor penetration of the active molecule. mXRF could be an elegant way to map the distribution of Pt inside cancerous cells at the micrometer scale. Pt and Zn are only two of the numerous trace elements that mXRF can detect; heavy metal intoxication diagnosis and the toxicity mechanism probably could also benefit from this innovative technique