Euryhaline ecology of early tetrapods revealed by stable isotopes.

The fish-to-tetrapod transition-followed later by terrestrialization-represented a major step in vertebrate evolution that gave rise to a successful clade that today contains more than 30,000 tetrapod species. The early tetrapod Ichthyostega was discovered in 1929 in the Devonian Old Red Sandstone sediments of East Greenland (dated to approximately 365 million years ago). Since then, our understanding of the fish-to-tetrapod transition has increased considerably, owing to the discovery of additional Devonian taxa that represent early tetrapods or groups evolutionarily close to them. However, the aquatic environment of early tetrapods and the vertebrate fauna associated with them has remained elusive and highly debated. Here we use a multi-stable isotope approach (δ13C, δ18O and δ34S) to show that some Devonian vertebrates, including early tetrapods, were euryhaline and inhabited transitional aquatic environments subject to high-magnitude, rapid changes in salinity, such as estuaries or deltas. Euryhalinity may have predisposed the early tetrapod clade to be able to survive Late Devonian biotic crises and then successfully colonize terrestrial environments.

Record of Nile seasonality in Nubian neonates.

The oxygen isotope compositions of bones (n = 11) and teeth (n = 20) from 12 Sudanese individuals buried on Sai Island (Nubia) were analysed to investigate the registration of the evolution of the Nile environment from 3700 to 500 years BP and the potential effects of ontogeny on the oxygen isotope ratios. The isotopic compositions were converted into the composition of drinking water, ultimately originating from the Nile. δ18O values decrease during ontogeny; this is mainly related to breastfeeding and physiology. Those of neonates present very large variations. Neonates have a very high bone turnover and are thus able to record seasonal δ18O variations of the Nile waters. These variations followed a pattern very similar to the present one. Nile δ18O values increased from 1.4 to 4.4 ‰ (Vienna Standard Mean Ocean Water) from the Classic Kerma (∼3500 BP) through the Christian period (∼1000 BP), traducing a progressive drying of Northeast Africa.

Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection.

We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.

Laser-induced breakdown spectroscopy: a new approach for nanoparticle's mapping and quantification in organ tissue.

Emission spectroscopy of laser-induced plasma was applied to elemental analysis of biological samples. Laser-induced breakdown spectroscopy (LIBS) performed on thin sections of rodent tissues: kidneys and tumor, allows the detection of inorganic elements such as (i) Na, Ca, Cu, Mg, P, and Fe, naturally present in the body and (ii) Si and Gd, detected after the injection of gadolinium-based nanoparticles. The animals were euthanized 1 to 24 hr after intravenous injection of particles. A two-dimensional scan of the sample, performed using a motorized micrometric 3D-stage, allowed the infrared laser beam exploring the surface with a lateral resolution less than 100 µm. Quantitative chemical images of Gd element inside the organ were obtained with sub-mM sensitivity. LIBS offers a simple and robust method to study the distribution of inorganic materials without any specific labeling. Moreover, the compatibility of the setup with standard optical microscopy emphasizes its potential to provide multiple images of the same biological tissue with different types of response: elemental, molecular, or cellular.

Mineral maturity and crystallinity index are distinct characteristics of bone mineral.

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2-4 mum thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis.

Bone stiffness in children: part I. In vivo assessment of the stiffness of femur and tibia in children.

Although there are many publications concerning the mechanical behavior of adult bone, there are few data about mechanical properties of children's bone. In vivo bone stiffness measurement with Orthometer device has been validated and extensively used in adults to assess bone healing after fracture or lengthening. We hypothesized that in vivo stiffness measurement with Orthometer was applicable in children and was correlated with age, height, body weight, and corpulence index. The purpose was to establish baseline stiffness values for femur and tibia in growing children.Sixteen bone measurements (7 femurs and 9 tibias) were obtained during application of an external fixator for leg lengthening in 11 children aged between 5.5 and 16.7 years. A 3-point bending test with an Orthometer was carried out on the intact bone (before osteotomy) under general anesthesia. The anteroposterior stiffness measurement was successful in all children of the series, aged from 5.5 to 16.7 years. A wide variation of femoral and tibial bone stiffness values were observed. The use of a unique value as in adults as the end point of bending stiffness during bone healing process is not possible for children. The anteroposterior bone stiffness was found to have linear correlation with children's height and body weight, but not with age and corpulence indexes. The original data obtained by this study will give a stiffness reference for height and weight and could be useful as reference values for monitoring of healing process after fracture or limb lengthening.

Bone stiffness in children: part II. Objectives criteria for children to assess healing during leg lengthening.

BACKGROUND: The decision when to remove the frame after limb lengthening through standard distraction osteogenesis remains a challenge. Multiple studies have attempted to find objective criteria to assess bone healing after fracture or bone lengthening. However, there is a paucity of such data for the pediatric population. The purpose of this study was to correlate data obtained after dual-energy x-ray absorptiometry (DXA) measurement and bending stiffness in children to find an end-point value for the safe removal of an external fixation device. METHODS: We investigated 16 consecutive children aged between 5.5 and 16.7 years who had 22 lengthenings by callotasis. Twelve femurs and 10 tibiae were lengthened with a monoplane Orthofix external fixator. Fifty simultaneous measurements of bending bone stiffness measured with an Orthometer and DXA scans (bone mineral content [BMC], bone mineral density, volumetric bone mineral density, BMC/1 cm, Area/1 cm, BMC/1 cm, Area) were obtained during healing process. Four femoral fractures were reported after the removal of the external fixation device. Linear regression analysis was used to calculate the squared correlation coefficients for the relation between the DXA scans and the mechanical tests measuring bone stiffness. RESULTS: The bone stiffness measurement of the intact bone was compared with consecutive measurements of the bone stiffness of the regenerate, and it was expressed as a percentage (coefficient). We compared the BMC of the regenerate with the same bone area of the opposite limb. The best correlation was observed for anteroposterior (AP) bone stiffness coefficient and BMC coefficient (R = 0.82). The linear equation was BMC coefficient = 0.5 x AP stiffness coefficient + 30. The end point of 75% of BMC of the regenerate corresponds to 75% of the AP stiffness on DXA scanning; this is the time when we should consider safe removal of the fixator. CONCLUSIONS: Our method of comparing bone stiffness and DXA measurements gives an objective healing end point for every patient irrespective of his or her size. This method could allow noninvasive measurement of the end point and identified at-risk population of children, reducing regenerate fracture after bone lengthening.

Long-term strontium ranelate administration in monkeys preserves characteristics of bone mineral crystals and degree of mineralization of bone.

UNLABELLED: In monkeys, long-term strontium ranelate administration results in a dose-dependent bone strontium uptake (mainly into newly formed bone) that preserves the degree of mineralization of bone and the bone mineral at the crystal level, showing its safety at bone mineral level. INTRODUCTION: Strontium ranelate simultaneously increases bone formation and decreases bone resorption, leading to prevention of bone loss and increase in bone mass and bone strength in normal and ovariectomized rats. This study investigated the interactions of stable strontium (Sr) with bone mineral in monkeys after long-term strontium ranelate treatment and after a period of treatment withdrawal. MATERIALS AND METHODS: Iliac bone was obtained from untreated monkeys, monkeys at the end of a 52-week strontium ranelate administration (200, 500, 1250 mg/kg/day orally), and in parallel groups 10 weeks after the end of strontium ranelate administration (same three doses; n = 3-7). Sr uptake and distribution in bone mineral were quantified by X-ray microanalysis, changes at the crystal level by X-ray diffraction, and the degree of mineralization of bone (DMB) by quantitative microradiography. RESULTS: After strontium ranelate administration, dose-dependent Sr uptake occurred into cortical and cancellous bone, with higher content (1.6 times) in new than in old bone. This Sr uptake decreased (50%) 10 weeks after treatment withdrawal; the decrease occurred almost exclusively in new bone. At the end of strontium ranelate treatment and after its withdrawal, a preservation of crystal characteristics was observed, suggesting that Sr was only faintly linked to crystals by ionic substitution and of DMB. CONCLUSIONS: These results show the absence of a deleterious effect of long-term strontium ranelate treatment on bone mineralization, confirming the histomorphometric observations made in postmenopausal osteoporotic women treated with strontium ranelate.