Biological monitoring of chemical exposure : toxicokinetic differences due to age and sex

Human biomonitoring is a widely used method in the assessment of occupational exposure to chemical substances and recommended biological limits are published periodically for interpretation and decision-making. However, it is increasingly recognized that a large variability is associated with biological monitoring, making interpretation less efficient than assumed. In order to improve the applicability of biological monitoring, specific factors responsible for this variability should be identified and their contribution quantified. Among these factors, age and sex are easily identifiable, and present knowledge about pharmaceutical chemicals suggests that they play an important role on the toxicokinetics of occupational chemical agents, and therefore on the biological monitoring results.The aim of the present research project was to assess the influence of age and sex on biological indicators corresponding to organic solvents. This has been done experimentally and by toxicokinetic computer simulation. Another purpose was to explore the effect of selected CYP2E1 polymorphisms on the toxicokinetic profile.Age differences were identified by numerical simulations using a general toxicokinetic model from a previous study which was applied to 14 chemicals, representing 21 specific biological entities, with, among others, toluene, phenol, lead and mercury. These models were runn with the modified parameters, indicating in some cases important differences due to age. The expected changes are mostly of the order of 10-20 %, but differences up to 50 % were observed in some cases. These differences appear to depend on the chemical and on the biological entity considered.Sex differences were quantified by controlled human exposures, which were carried out in a 12 m3 exposure chamber for three organic solvents separately: methyl ethyl ketone, 1-methoxy-2-propanol and 1,1,1-trichloroethane. The human volunteer groups were composed 12 of ten young men and fifteen young women, the latter subdivided into those with and without hormonal contraceptive. They were exposed during six hours at rest and at half of the threshold limit value. The kinetics of the parent compounds (organic volatiles) and their metabolite(s) were followed in blood, urine and expired air over time. Analyses of the solvent and their metabolites were performed by using headspace gas chromatography, CYP2E1 genotypes by using PCR-based RFLP methods. Experimental data were used to calibrate the toxicokinetic models developed for the three solvents. The results obtained for the different biomarkers of exposure mainly showed an effect on the urinary levels of several biomarkers among women due to the use of hormonal contraceptive, with an increase of about 50 % in the metabolism rate. The results also showed a difference due to the genotype CYP2E1*6, when exposed to methyl ethyl ketone, with a tendency to increase CYP2E1 activity when volunteers were carriers of the mutant allele. Simulations showed that it is possible to use simple toxicokinetic tools in order to predict internal exposure when exposed to organic solvents. Our study suggests that not only physiological differences but also exogenous sex hormones could influence CYP2E1 enzyme activity. The variability among the urinary biological indicators levels gives evidence of an interindividual susceptibility, an aspect that should have its place in the approaches for setting limits of occupational exposure.

Chemical probes that differentially modulate peroxisome proliferator-activated receptor alpha and BLTR, nuclear and cell surface receptors for leukotriene B(4).

Peroxisome proliferator-activated receptor alpha (PPARalpha)is a nuclear receptor for various fatty acids, eicosanoids, and hypolipidemic drugs. In the presence of ligand, this transcription factor increases expression of target genes that are primarily associated with lipid homeostasis. We have previously reported PPARalpha as a nuclear receptor of the inflammatory mediator leukotriene B(4) (LTB(4)) and demonstrated an anti-inflammatory function for PPARalpha in vivo (Devchand, P. R., Keller, H., Peters, J. M., Vazquez, M., Gonzalez, F. J., and Wahli, W. (1996) Nature 384, 39-43). LTB(4) also has a cell surface receptor (BLTR) that mediates proinflammatory events, such as chemotaxis and chemokinesis (Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., and Shimizu, T. (1997) Nature 387, 620-624). In this study, we report on chemical probes that differentially modulate activity of these two LTB(4) receptors. The compounds selected were originally characterized as synthetic BLTR effectors, both agonists and antagonists. Here, we evaluate the compounds as effectors of the three PPAR isotypes (alpha, beta, and gamma) by transient transfection assays and also determine whether the compounds are ligands for these nuclear receptors by coactivator-dependent receptor ligand interaction assay, a semifunctional in vitro assay. Because the compounds are PPARalpha selective, we further analyze their potency in a biological assay for the PPARalpha-mediated activity of lipid accumulation. These chemical probes will prove invaluable in dissecting processes that involve nuclear and cell surface LTB(4) receptors and also aid in drug discovery programs.

Characterization of rapeseed (Brassica napus) oils by bulk C, O, H, and fatty acid C stable isotope analyses

Rapeseed (Brassica napus) oils differing in cultivar, sites of growth, and harvest year were characterized by fatty acid concentrations and carbon, hydrogen, and oxygen stable isotope analyses of bulk oils (delta(13)C(bulk), delta(2)H(bulk), delta(18)O(bulk) values) and individual fatty acids (delta(13)C(FA)). The delta(13)C(bulk), delta(2)H(bulk), and delta(18)O(bulk) values were determined by continuous flow combustion and high-temperature conversion elemental analyzer isotope ratio mass spectrometry (EA/IRMS, TC-EA/IRMS). The delta(13)C(FA) values were determined using gas chromatography-combustion isotope ratio mass spectrometry (GC/C/IRMS). For comparison, other C(3) vegetable oils rich in linolenic acid (flax and false flax oils) and rich in linoleic acid (poppy, sunflower, and safflower oils) were submitted to the same chemical and isotopic analyses. The bulk and molecular delta(13)C values were typical for C(3) plants. The delta(13)C value of palmitic acid (delta(13)C(16:0)) and n-3 alpha-linolenic acid (delta(13)C(18:3n-3)) differed (p < 0.001) between rape, flax, and poppy oils. Also within species, significant differences of delta(13)C(FA) were observed (p < 0.01). The hydrogen and oxygen isotope compositions of rape oil differed between cultivars (p < 0.05). Major differences in the individual delta(13)C(FA) values were found. A plant-specific carbon isotope fractionation occurs during the biosynthesis of the fatty acids and particularly during desaturation of C(18) acids in rape and flax. Bulk oil and specific fatty acid stable isotope analysis might be useful in tracing dietary lipids differing in their origin.

Development and validation of a gas chromatography-negative chemical ionization tandem mass spectrometry method for the determination of ethyl glucuronide in hair and its application to forensic toxicology.

Ethyl glucuronide (EtG) is a minor and direct metabolite of ethanol. EtG is incorporated into the growing hair allowing retrospective investigation of chronic alcohol abuse. In this study, we report the development and the validation of a method using gas chromatography-negative chemical ionization tandem mass spectrometry (GC-NCI-MS/MS) for the quantification of EtG in hair. EtG was extracted from about 30 mg of hair by aqueous incubation and purified by solid-phase extraction (SPE) using mixed mode extraction cartridges followed by derivation with perfluoropentanoic anhydride (PFPA). The analysis was performed in the selected reaction monitoring (SRM) mode using the transitions m/z 347-->163 (for the quantification) and m/z 347-->119 (for the identification) for EtG, and m/z 352-->163 for EtG-d(5) used as internal standard. For validation, we prepared quality controls (QC) using hair samples taken post mortem from 2 subjects with a known history of alcoholism. These samples were confirmed by a proficiency test with 7 participating laboratories. The assay linearity of EtG was confirmed over the range from 8.4 to 259.4 pg/mg hair, with a coefficient of determination (r(2)) above 0.999. The limit of detection (LOD) was estimated with 3.0 pg/mg. The lower limit of quantification (LLOQ) of the method was fixed at 8.4 pg/mg. Repeatability and intermediate precision (relative standard deviation, RSD%), tested at 4 QC levels, were less than 13.2%. The analytical method was applied to several hair samples obtained from autopsy cases with a history of alcoholism and/or lesions caused by alcohol. EtG concentrations in hair ranged from 60 to 820 pg/mg hair.

Terrorisme et médecins de premier recours: le risque chimique [Terrorism and medicine of first aid: chemical risk].

Cet article décrit, à l'intention des mdéecins de rpremier recours, les principes de base d'une action de secours lors d'un attentat (ou d'un accident) chimique impliquant de nombreuses victimes intoxiquées et/ou contaminées.

Antidote treatment for cyanide poisoning with hydroxocobalamin causes bright pink discolouration and chemical-analytical interferences.

Here we report the case of a 70-year-old woman who committed suicide by cyanide poisoning. During resuscitation cares, she underwent an antidote treatment by hydroxocobalamin. Postmortem investigations showed marked bright pink discolouration of organs and fluids, and a lethal cyanide blood concentration of 43 mg/L was detected by toxicological investigation. Discolouration of hypostasis and organs has widely been studied in forensic literature. In our case, we interpreted the unusual pink coloration as the result of the presence of hydroxocobalamin. This substance is a known antidote against cyanide poisoning, indicated because of its efficiency and poor adverse effects. However, its main drawback is to interfere with measurements of many routine biochemical parameters. We have tested the potential influence of this molecule in some routine postmortem investigations. The results are discussed.

Investigation phytochimique d'une plante médicinale malgache Hypoestes serpens (Vahl) R. Br. (Acanthaceae) variété glabre et étude comparative avec la variété poilue

Résumé A Madagascar, comme dans plusieurs pays en développement, une grande partie de la population utilise les plantes pour se soigner. Plusieurs espèces des plantes sont ainsi utilisées en médecine traditionnelle malgache. Par ailleurs, la plupart de ces plantes ne font l'objet que de très peu d'étude scientifique. En effet, dans le cadre de l'investigation phytochimique de plantes utilisées en médecine traditionnelle malgache et dans la recherche des nouvelles substances biologiquement actives, Hypoestes serpens (Vahl) R. Br. (Acanthaceae) a été étudiée. Elle se présente sous deux variétés (glabre et poilue) qui sont tous utilisées dans la région sud-centre de Madagascar pour traiter la blennorragie. De l'extrait dichlorométhanique des feuilles de H. serpens (Vahl) R. Br. variété glabre, 12 diterpénoides dont 8 nouveaux ont été isolés. Ils ont tous montré une activité antifongique contre un champignon pathogène des plantes, Cladosporium cucumerinum, dans la bioautographie directe sur CCM. Quelques-uns ont également présenté une activité contre une levure saprophyte chez l'homme, Candida albicans et une activité inhibitrice de l'enzyme acétylcholinesterase. Les diterpènoïdes sont déjà considérés comme les principaux métabolites secondaires du genre Hypoestes. Le fractionnement de l'extrait méthanolique a conduit à l'isolement de 5 glycosides des flavonoïdes dont 4 sous formes C-g,lycosides qui n'ont jamais été identifiés dans la famille Acanthaceae. Ces flavonoïdes ont présenté une activité antiradicalaire contre le DPPH. Le fractionnement et la purification des extraits ont été effectués à l'aide des différentes techniques chromatographiques telles que la chromatographie sur colonne ouverte, la filtration sur gel, la chromatographie liquide à haute pression, la chromatographie liquide à moyenne pression et la chromatographie liquide à basse pression. Par ailleurs, les structures des composés isolés ont été élucidées par des techniques spectroscopiques (UV, MS, RMN) et de méthode chimique (hydrolyse acide). En plus de ces techniques, certaines méthodes physiques (cristallographie par rayons-X, mesure de rotation optique) ont été réalisées pour confirmer certaines structures. Comme l'espèce Hypoestes serpens (Vahl) R. Br. se présente en deux variétés, une étude comparative a été effectuée. Cette étude avait montré que ces deux variétés ont une activité biologique similaire. Finalement, une technique analytique couplée, HPLC-UV-APC1-MS a permis de montrer la présence de toutes les substances isolées de la variété glabre dans la variété poilue. Second résumé Depuis des milliers d'almées, l'homme utilise les plantes pour se soigner. De nos jours, même avec le développement de la médecine moderne, la phytothérapie reste toujours la forme des soins de santé abordable et accessible pour la majorité des populations rurales des pays en développement. En outre, les plantes médicinales constituent une source potentielle de molécules biologiquement actives pour les industries pharmaceutiques et actuellement, on estime que 25% des médicaments commercialisés dans le monde sont à base de plantes Dans le cadre de la recherche des nouvelles molécules à intérêt thérapeutique qui pourraient devenir un médicament ou un modèle de structure ("lead compound") pour le développement de nouveaux médicaments, nous avons fait une étude sur l'espèce, Hypoestes serpens (Vahl) R. Br, plante utilisée en médecine traditionnelle malgache. Cette espèce existe en deux variétés, une glabre et une autre poilue qui sont tous utilisées dans la région sud-centre de Madagascar pour traiter la blennorragie. Par ailleurs, les tradipraticiens utilisent de préférence la variété poilue. Dans la première partie de ce présent travail, une investigation phytochimique de H serpens, variété glabre (variété moins utilisée) a d'abord été effectuée afm d'isoler et d'identifier le maximum des molécules biologiquement actives qu'elle contient. De ce fait, 17 composés dont 8 nouveaux ont été isolés. Les potentiels d'activités thérapeutiques des substances isolées ont ensuite été dépistés sur les différents cibles suivants.: deux souches de champignons (Cladosporium cucumerinum et Candida albicans), l'enzyme acétylcholinesterase et le radical DPPH. La deuxième partie de ce travail a été consacrée sur l'étude comparative des deux variétés (glabre et poilue) de H. serpens à la fois sur le plan biologique et sur le plan phytochimique. A l'issue de cette comparaison, nous avons constaté que l'utilisation de ces deux variétés en médecine traditionnelle malgache n'est pas un hasard ; les deux variétés avaient présenté une activité biologique très remarquable et contiennent les mêmes substances actives. Ces résultats démontrent les potentiels thérapeutiques de H serpens en médecine traditionnelle malgache et pourraient également encourager les tradipraticiens à utiliser la variété glabre tout en protégeant la variété poilue qui est en voie de disparition actuellement. En bref, l'investigation phytochimique de H. serpens justifiée par l'isolement et l'identification de certains de ses principes actifs ouvre la voie aux recherches des médicaments d'origine naturelle. Abstract In Madagascar, as in many developing countries, most people use plants to cure. A large number of plant species are employed in Malagasy traditional medicine. Moreover, most of these plants have been subject only very little scientific study. As part of a phytochemical investigation of plants used in Malagasy traditional medicine and in the search for new biologically active substances, Hypoestes serpens (Vah1) R.Br. (Acanthaceae) was investigated. This species exists in two varieties (glabrous and hairy) which are used in the south-center part of Madagascar to treat gonorrhoea. From the dichloromethane extract of the leaves of H. serpens (Vah1) R. Br. glabrous variety, 12 diterpenoids 8 of which were new, were isolated. They showed antifungal activity against the plant pathogen Cladosporium cucumerinum, in the direct TLC bioautography. Some of them also had activity against the yeast Candida athicans and inhibited acetylcholinesterase. The diterpenes are considered as the principal secondary metabolites of the genus Hypoestes. Fractionation of the methanol extract led to the isolation of 5 flavonoid glycosides, 4 of which were C-glycosides, never before identified in the Acanthaceae family. These flavonoids showed radical scavenging activity against DPPH. The fractionation and the purification of the extracts were achieved by different chromatographic techniques such as open-column chromatography, gel filtration, high- pressure liquid chromatography, medium-pressure liquid chromatography and low-pressure liquid chromatography. Moreover, the structures of the isolated compounds were elucidated by spectroscopic techniques (UV, MS, NMR) and chemical technique (acid hydrolysis). In addition, some physical methods (X-ray crystallography, measurement of optical rotation) were performed to confirm some structures. As the species Hypoestes serpens (Vah1) R. Br. is present in two varieties, a comparative study was carried out. This study showed that these two varieties had similar biological activity. Finally, a coupled analytical technique HPLC-UV-APCI-MS showed the presence of the same compounds in both the glabrous and hairy varieties.

Impaired chemical coupling of cerebral blood flow is compatible with intact neurological outcome in neonates with perinatal risk factors.

Early detection of pathophysiological factors associated with permanent brain damage is a major issue in neonatal medicine. The aim of our study was to evaluate the significance of the CO2 reactivity of cerebral blood flow (CBF) in neonates with perinatal risk factors. Fourteen ventilated neonates with perinatal risk factors (pathological cardiotocogramm, low cord pH, postpartal encephalopathy) were enrolled into this prospective study. The study was performed 18-123 h after birth. CBF was measured using the noninvasive intravenous 133Xe method. Two measurements were taken with a minimal PaCO2-difference of 5 mm Hg. From the two CBF values the CO2 reactivity was calculated. Outcome was evaluated 1 year after birth. The CBF values at a lower PaCO2 ranged from 6.6 to 115. 2 ml/100 g brain issue/min (median = 18.2) and at a higher PaCO2 level from 7.1 to 125.7 ml/100 g brain tissue/min (median = 18.75). The calculated CO2 reactivity ranged from -9.6 to 6.6% (median 1.1%) change in CBF/mm Hg change in PaCO2. CO2 reactivity correlated with lowest pH (r2 = 0.35, p = 0.02). Two infants died, one of neonatal sepsis, the other of heart failure. Neurological outcome at the age of 1 year was normal in 11 patients, 1 had severe cerebral palsy. From the 12 surviving patients the patient with severe neurological deficit showed the highest CBF values (125.7 ml/100 g/min). Impaired chemical coupling of cerebral blood flow is compatible with intact neurological outcome in neonates with perinatal risk factors. CO2 reactivity in these newborns correlates with the lowest pH and may reflect the severity of perinatal asphyxia.

Origin of needle fibre calcite (NFC) : a geochemical approach

ABSTRACTNeedle fibre calcite (NFC) is one of the most widespread habits of pedogenic calcite. It is a monocrystal of calcite, in the shape of a needle, with a diameter of one micron and a length between 4 and 103 times its width. NFC occurs in soils with different macroscopic and microscopic morphologies. Macroscopically, two main habits of NFC exist: "cotton ball'Mike clusters and as "powder" coating on pebbles inside the soil. It can also act as nucleation sites for precipitation of calcite cements of purely physicochemical origin (LCC - Late Calcitic Cement). Although many studies have been conducted on needle fibre calcite, its origin remains a subject of debate. The NFC having never been reproduced in the laboratory whatever the considered approach, the processes responsible for its precipitation as a so particular morphology remain unexplained. The shift between the length orientation of the needle crystal and the normal axis of calcite growth (c-axis) is also unresolved.Samples taken in two soils observed in quarries (Villiers and Savagnier) in the Swiss Jura Mountains are used to investigate the processes involved in the formation of these calcite crystals in pedogenic environments. Three groups of microscopic morphologies are distinguished: (i) simple needles (SN), (ii) simple needles with overgrowths (SNO), and (iii) simple needles with nanofibres (SNN), nanofibres being either organic or mineral in nature. These groups correspond to different stages in the formation and evolution of NFC.Comparison of carbon and oxygen isotope compositions of NFC with LCC, in relationship with the composition of the carbonate host rock (CHR), and the carbon isotope signature of dissolved inorganic carbon (DIC) from the soil waters, indicates that both NFC and LCC are precipitated in isotopic equilibrium with the soil solution. Similar Ô13C and Ô180 values of the elongated NFC and the rhombohedral calcite crystals of the LCC suggest that the precipitation of these different calcite habits is not due to changes in physicochemical conditions. The growth of NFC crystals inside an organic mould formed by the fungal hyphae could explain the formation of calcite ciystals in the shape of a needle in isotopic equilibrium with the local environment.Strontium and calcium isotope compositions of the three microscopic groups of NFC and LCC were also studied, in order to determine the origin of calcium (Ca2+) entrapped in the calcite lattice and to elucidate the processes responsible for the precipitation of NFC. The 87Sr/86Sr ratio of the SN is closer to the 87Sr/86Sr ratio of the carbonate host rock than the LCC, SNO, and SNN. This could be another clue for the formation of SN inside fungal hyphae, because fungi are known to dissolve the rocks to release and translocate through their hyphae nutrients necessary for their growth. SN and SNN are depleted in Sr and enriched in ^Ca compared to the LCC. In the context of Villiers quarry, where the two ciystal shapes precipitate at similar temperature (in a range of 0,6°C), such variations are the result of a slower precipitation rate of NFC, which is inconsistent with a purely physicochemically precipitated elongate crystal.Finally, NFC is enriched in major and trace elements (i.e. Fe, Zn, Cu, and Mo) compared to the LCC. This enrichment is ascribed to modification in precipitation processes between the NFC and LCC. Right now, it is not possible to preclude the influence of the particular shape of NFC or the biological influence. REEs are not fractionated in NFC, contrary to LCC. Thus, NFC does not precipitate from a percolation solution circulating downward the soil, which should lead to the fractionation of the REEs. As explained above, fungi, are able to dissolve and translocate nutrients. This kind of processes allows releasing elements in the soil solution without fractionation and could explain the particular chemical signature of NFC regarding the REEs.The geochemical approach to investigate the origin of NFC presented in this study does not allow providing direct clues to the fungal origin of NFC, but brings several new insights in the understanding of the formation of such a particular mineral, calcite needles, by precluding definitively their physicochemical origin.RESUMELa calcite en aiguilles (NFC) est l'une des formes les plus ubiquiste de calcite pédogénique. Il s'agit d'un monocrystal de calcite d'un diamètre d'un micron et d'une longueur 4 à 102 fois supérieure à sa largeur. A l'échelle macroscopique, la NFC a été observée sous deux principaux aspects : l'une « cotonneuse » et l'autre formant un mince croûte autour des graviers du sol. La NFC peut également servir de support à la nucléation de ciments secondaires précipités de manière purement physico-chimique (LCC). Malgré les nombreuses études menées sur la NFC, son origine demeure encore inconnue. A ce jour, aucune expérience en laboratoire n'a permis de créer de la calcite en aiguilles, et ce, quelque soit l'approche abordée. Par conséquent, les processus précis responsables de la précipitation calcite avec une telle morphologie restent inconnus. Le décalage existant entre l'axe d'allongement des aiguilles de calcite et l'axe normal de croissance de la calcite (axe c) reste inexpliqué.Des échantillons de NFC, LCC, roche mère, eau de pluie des différents horizons du sol ont été prélevés principalement au front de deux carrières de graviers, ainsi que dans un profil de sol adjacent à ces carrières, dans le but de mieux comprendre les processus à l'origine de la précipitation de calcite en forme d'aiguille. Trois micro-morphologies ont été distinguées: les aiguilles simples (SN), les aiguilles simples avec surcroissances calcitiques (SNO) et enfin les aiguilles simples avec nanofibres (SNN), celles-ci pouvant être de minérales ou organiques. Ces groupes, d'après nos résultats et les études antérieures pourraient correspondre à différentes étapes de formation de la calcite en aiguilles.Dans un premier temps, la comparaison des signatures isotopiques de la calcite en aiguilles, du LCC, de la roche mère et du carbone inorganique dissout dans la solution du sol (CID) indique que la NFC, tout comme le LCC, précipite en équilibre avec la solution du sol. Les valeurs similaires en Ô13C et δ180 de cristaux de calcite allongés (NFC) et rhombohédriques (LCC) formés dans un même milieu suggère que ces différences morphologiques ne peuvent pas être attribuées à des modifications purement physico-chimiques. La croissance de NFC à l'intérieur d'un moule organique comme les hyphes de champignons semble être la seule hypothèse plausible permettant d'expliquer la formation de monocrystaux allongés de calcite en équilibre avec leur environnement.La composition isotopique en strontium (Sr) et calcium (Ca) des LCC et des trois micro¬morphologies de la NFC ont été étudiées également, afin de déterminer l'origine du Ca2+ présent dans le réseau cristallin de la calcite en aiguilles, ainsi que les processus responsables de la formation de NFC. Les valeurs du rapport 87Sr/86$r de la forme SN sont les plus proches de celles de la roche mère par rapport aux formes SNN et SNO et du LCC. Ceci pourrait être un nouvel indice de l'implication des champignons dans la précipitation de calcite en aiguilles, puisqu'ils sont connus pour avoir la capacité de dissoudre les roches afin de libérer les nutriments nécessaires à leur croissance, ainsi que de les transloquer par leurs hyphes. De plus, les formes SN et SNN sont appauvries en Sr et enrichies en "Ca, comparativement au LCC. Dans le sol étudié, tous les carbonates de calcium précipitent à la même température, par conséquent, de telles variations sont dues à un taux de précipitation plus lent de SN et SNN, ce qui est contradictoire avec l'hypothèse physico-chimique. Pour finir, la NFC est enrichie en certains éléments majeurs et traces (i.e. Fe, Zn, Cu et Mo) par rapport au LCC. Ceci peut être attribué à différents processus de formation entre la NFC et le LCC. Pour le moment il est impossible d'exclure l'influence de la forme particulière de la NFC ou celle du champignon. Les terres rares (REEs) ne sont pas fractionnées dans la NFC, contrairement au LCC. Ceci peut être expliqué par le fait que la NFC précipite à partir d'une solution qui n'a pas percolé à travers le sol. Les champignons en dissolvant les roches mettent en solution éléments sans les fractionner. L'approche géochimique de l'étude de la calcite en aiguilles ne permets pas de produire des preuves directes sur sa potentielle origine fongique, mais permet de mieux comprendre comment un minéral aussi singulier que la NFC peut se former. D'autre pare cette étude permets d'exclure définitivement l'hypothèse physico-chimique de l'origine de la calcite en aiguilles

Detection and chemical profiling of medicine counterfeits by Raman spectroscopy and chemometrics

Raman spectroscopy combined with chemometrics has recently become a widespread technique for the analysis of pharmaceutical solid forms. The application presented in this paper is the investigation of counterfeit medicines. This increasingly serious issue involves networks that are an integral part of industrialized organized crime. Efficient analytical tools are consequently required to fight against it. Quick and reliable authentication means are needed to allow the deployment of measures from the company and the authorities. For this purpose a method in two steps has been implemented here. The first step enables the identification of pharmaceutical tablets and capsules and the detection of their counterfeits. A nonlinear classification method, the Support Vector Machines (SVM), is computed together with a correlation with the database and the detection of Active Pharmaceutical Ingredient (API) peaks in the suspect product. If a counterfeit is detected, the second step allows its chemical profiling among former counterfeits in a forensic intelligence perspective. For this second step a classification based on Principal Component Analysis (PCA) and correlation distance measurements is applied to the Raman spectra of the counterfeits.

Hydrogen and oxygen isotope behaviors during variable degrees of upper mantle melting: Example from the basaltic glasses from Macquarie Island

We present measurements of hydrogen and oxygen isotopes in MORB glasses from Macquarie Island (SW. Pacific Ocean) coupled with determination of bulk H2O content by two independent techniques: total dehydration and FTIR. The incompatible trace elements in these glasses vary by a factor of 12 to 17, with K2O varying from 0.1 to 1.7 wt.%; these ranges reflect a variable degree of closed-system mantle melting, estimated from 1 to 15%. Water concentrations determined by the two techniques match well, yielding a range from 0.25 to 1.49 wt.% which correlates positively with all of the measured incompatible trace elements, suggesting that water is un-degassed, and behaves conservatively during mantle melting. Also, the agreement between the FTIR-determined and extracted water contents gives us confidence that the measured isotopic values of hydrogen reflect that of the mantle. Comparison of the range of water content with that of other incompatible trace elements allows estimation of the water partition coefficient in lherzolite, 0.0208 (ranging from 0.017 to 0.023), and the water content in the source, 386 ppm (ranging from 370 to 440 ppm). We observe a fairly narrow range in delta D and delta O-18 values of -75.5 +/- 4.5 parts per thousand and 5.50 +/- 0 .05 parts per thousand respectively, that can be explained by partial melting of normal lherzolitic mantle. The measured delta D and delta O-18 values of Macquarie Island glasses that range from nepheline- to hypersthene-normative, and from MORB to EMORB in composition, are identical to those in average global MORB. The observed lack of variation of delta D and delta O-18 with 1 to 15% degree of mantle melting is consistent with a bulk melting model of delta D and delta O-18 fractionation, in which water is rapidly scavenged into the first partial melt. The narrow ranges of delta D and delta O-18 in normal mantle are mostly due to the buffering effect of clino- and orthopyroxenes in the residual assemblage; additionally, fast ``wet'' diffusion of oxygen and hydrogen isotopes through the melting regions may further smooth isotopic differences. (C) 2012 Elsevier B.V. All rights reserved.

Chemical and isotopic equilibrium between CO2 and CH4 in fumarolic gas discharges: Generation of CH4 in arc magmatic-hydrothermal systems

The chemical and isotopic composition of fumarolic gases emitted from Nisyros Volcano, Greece, and of a single gas sample from Vesuvio, Italy, was investigated in order to determine the origin of methane (CH,) within two subduction-related magmatic-hydrothermal environments. Apparent temperatures derived from carbon isotope partitioning between CH4 and CO2 of around 340degreesC for Nisyros and 470degreesC for Vesuvio correlate well with aquifer temperatures as measured directly and/or inferred from compositional data using the H2O-H-2-CO2-CO-CH4 geothermometer. Thermodynamic modeling reveals chemical equilibrium between CH4, CO2 and H2O implying that carbon isotope partitioning between CO2 and CH, in both systems is controlled by aquifer temperature. N-2/(3) He and CH4/(3) He ratios of Nisyros fumarolic gases are unusually low for subduction zone gases and correspond to those of midoceanic ridge environments. Accordingly, CH4 may have been primarily generated through the reduction of CO, by H, in the absence of any organic matter following a Fischer-Tropsch-type reaction. However, primary occurrence of minor amounts of thermogenic CH4 and subsequent re-equilibration with co-existing CO2 cannot be ruled out entirely- CO2/He-3 ratios and delta(13)C(CO2) values imply that the evolved CO2 either derives from a metasomatized mantle or is a mixture between two components, one outgassing from an unaltered mantle and the other released by thermal breakdown of marine carbonates. The latter may contain traces of organic matter possibly decomposing to CH4 during thermometamorphism. Copyright (C) 2004 Elsevier Ltd.

Epidote in hydrous mafic magmas : near solidus phase relations in the lower crust

Crystallisation of hydrous mafic magmas at high pressure is a subject of numerous petrologic and experimental studies since the last century and is mainly related to the process of continental crust formation and the possible link between mantle derived melts and low pressure granitoids. Albeit the sequence of crystallization is well constrained by experimental studies, the origin of exposed lower crustal rocks exposed on the earth surface is controversial. Ones line of argument is favouring high pressure crystallization of dry or wet mafic magmas, whereas others invoke partial melting of pre-existing crust. Therefore studies involving field, textural and chemical observations of exposed lower crust such as in Kohistan (Pakistan) or Talkeetna (Alaska) are crucial to understand the continental crust formation processes via arc magmatism. Epidote-bearing gabbros are very sparse and always associated with the deep part of continental crust (>30 km) as in the Kohistan Arc Complex (Pakistan) or in the Chelan Complex (western U.S.). Magmatic epidote is restricted to a small temperature interval above the water-saturated solidus of MORB and represent the last crystallizing liquids in lower crustal regions. However, epidote and melt stability at lower crustal pressures are not clearly established.¦The Chelan complex (western U.S.) at the base of the Cascadian Arc is composed mainly by peraluminous tonalité associated with gabbroic and ultramafic rocks and was traditionally interpreted as a migmatitic terrain. However field, chemical and mineralogical observations rather suggest a magmatic origin and point to a protracted crystallization at intermediate to high pressure ~ 1.0 GPa dominated by amphibole fractionation and followed by isobaric cooling down to 650°C. Crystal fractionation modelling using whole rock composition and field constraints is able to generate peraluminous tonalité. The modelled crystallisation sequence and the volume proportions are in agreement with experimental studies performed at these pressures. The Chelan complex was thus not formed during a partial melting event, but represent the sequence of crystallisation occurring at the base of the crust. Massive fractionation of hornblende is able to generate peraluminous tonalité without significant assimilation of crustal rock.¦Similarly to the Chelan complex, the base of the Kohistan arc is composed of cumulates derived by high pressure crystallization of hydrous magma. In garnet gabbros, epidote occurs as magmatic phase, crystallising from hydrous interstitial melt trapped between grain boundaries at lower crustal pressures (Ρ ~ 1.2 GPa) for temperature of (650-700 °C). Trace and REE signature in epidote indicate that epidote was formed through peritectic reaction involving garnet, clinopyroxene and plagioclase. At the beginning of the crystallisation epidote signature is dominated by REE content in the melt, whereas at the end the signature is dominated by reacting phases. Melt in equilibrium with epidote inferred from the partition coefficients available is similar to intrusive tonalité up the section indicating that hydrous melt was extracted from the garnet gabbros. In some gabbros epidote shows single homogeneous compositions, while in others coexisting epidote have different compositions indicating the presence of solvi along the Al-Fe3+ join. The overgowths are only observed in presence of paragonite in the assemblage, suggesting high water content. At high water content, the hydrous solidus is shift to lower temperature and probably intersects the solvi observed along the Al-Fe3+ join. Therefore, several compositions of epidote is stable at high water content.¦-¦La composition chimique de la croûte continentale est considérée comme similaire à celle du magmatisme calco-alcalin de marge continentale active (enrichissement en éléments mobiles dans les fluides, anomalies négatives en Nb, Ta et éléments à haut potentiel électronique, etc...). Cependant la nature andésitique de la croûte continentale (Si02 > 60 wt%), résultant des nombreuses intrusions de granitoïdes dans la croûte supérieure, est sujette à polémique et le lien entre les magmas dérivés du manteau et les roches évoluées de faible profondeur n'est pas clairement établi (fusion partielle de croûte basaltique, cristallisation fractionnée à haute pression, etc...).¦Les affleurements de croûte profonde sont rares mais précieux, car ils permettent d'observer les phénomènes se passant à grande profondeur. Le complexe de Chelan (Washington Cascades) en est un exemple. Formé à environ 30 km de profondeur, il est composé de roches gabbroïques et ultramafiques, ainsi que de tonalités, qui furent souvent interprétés comme le produit de la fusion partielle de la croûte. Cependant, les relations de terrain, la chimie des éléments majeurs et des éléments traces sont cohérentes avec l'évolution d'un complexe magmatique mafique dans la croûte profonde ou moyenne ( 1.0 GPa), dominée par le fractionnement de l'amphibole. Après son emplacement, le complexe a subi un refroidissement isobare jusqu'à des températures de l'ordre de 650 °C, déduit de la composition chimique des minéraux. Un bilan de masse contraint pax les observations de terrain permet de calculer la séquence et les volumes de fractionnement. Les faciès évolués légèrement hyperalumineux observés sur le terrain peuvent être générés par la cristallisation de 3 % de websterite à olivine, 12 % d'hornblendite à pyroxène 33 % d'hornblendite, 19 % de gabbros, 15 % de diorite et 2 % de tonalité. Nous montrons ainsi qu'une série de fractionnement contrôlée par l'amphibole permet de générer des tonalités sans assimilation de matériel crustal et l'exemple de Chelan illustre la viabilité de ce processus dans la formation de croûte continentale.¦Les réactions proches du solidus saturé en H20 dans les systèmes basaltiques à des pressions élevées restent énigmatiques. Diverses expériences tendent à montrer que l'épidote est stable dans ces conditions, mais rarement observée (décrite ?) comme phase primaire dans les systèmes naturels. Les épidotes trouvées dans les gabbros de Jijal (nord-Pakistan) montrent des textures de type .magmatique telles qu'observées dans les roches évoluées. Le contenu en terres rares de ces épidotes est très variable allant de signatures enrichies en terres rares légères impliquant la présence de liquide interstitiel à des signatures complètement déprimées en ces mêmes éléments, évoquant une cristallisation en coexistence avec du grenat. Ces diverses signatures reflètent un chemin de cristallisation en présence de liquide interstitiel et enregistrent des réactions péritectiques impliquant grenat, clinopyroxene et plagioclase à des pressions de ~ 1.2 GPa pour des températures de 650-700 °C. Cependant dans quelques échantillons deux ou trois compositions d'épidotes coexistent démontrant la présence de lacunes d'immiscibilité le long de la solution solide épidote-clinozoïsite. La forte teneur en H20 du liquide magmatique est certainement à l'origine de la coexistence de deux compositions distinctes.

Incidence and management of pulmonary embolism following spinal surgery occurring while under chemical thromboprophylaxis.

Patients undergoing spinal surgery are at risk of developing thromboembolic complications even though lower incidences have been reported as compared to joint arthroplasty surgery. Deep vein thrombosis (DVT) has been studied extensively in the context of spinal surgery but symptomatic pulmonary embolism (PE) has engaged less attention. We prospectively followed a consecutive cohort of 270 patients undergoing spinal surgery at a single institution. From these patients, only 26 were simple discectomies, while the largest proportion (226) was fusions. All patients received both low molecular weight heparin (LMWH) initiated after surgery and compressive stockings. PE was diagnosed with spiral chest CT. Six patients developed symptomatic PE, five during their hospital stay. In three of the six patients the embolic event occurred during the first 3 postoperative days. They were managed by the temporary insertion of an inferior vena cava (IVC) filter thus allowing for a delay in full-dose anticoagulation until removal of the filter. None of the PE patients suffered any bleeding complication as a result of the introduction of full anticoagulation. Two patients suffered postoperative haematomas, without development of neurological symptoms or signs, requiring emergency evacuation. The overall incidence of PE was 2.2% rising to 2.5% after exclusion of microdiscectomy cases. The incidence of PE was highest in anterior or combined thoracolumbar/lumbar procedures (4.2%). There is a large variation in the reported incidence of PE in the spinal literature. Results from the only study found in the literature specifically monitoring PE suggest an incidence of PE as high as 2.5%. Our study shows a similar incidence despite the use of LMWH. In the absence of randomized controlled trials (RCT) it is uncertain if this type of prophylaxis lowers the incidence of PE. However, other studies show that the morbidity of LMWH is very low. Since PE can be a life-threatening complication, LMWH may be a worthwhile option to consider for prophylaxis. RCTs are necessary in assessing the efficacy of DVT and PE prophylaxis in spinal patients.