Catalytic Enantioselective Total Synthesis of (+)–Lycoperdic Acid

A concise enantio- and stereocontrolled synthesis of (+)-lycoperdic acid is presented. The stereochemical control is based on iminium-catalyzed Mukaiyama–Michael reaction and enamine-catalyzed organocatalytic α-chlorination steps. The amino group was introduced by azide displacement, affording the final stereochemistry of (+)-lycoperdic acid. Penultimate hydrogenation and hydrolysis afforded pure (+)-lycoperdic acid in seven steps from a known silyloxyfuran.peerReviewe

Chronic exposure to uranium leads to iron accumulation in kidney rats cells

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Biokinetic models for rats exposed to repeated inhalation of uranium: implications for the monitoring of nuclear workers

For dose assessment following chronic or accidental inhalation of radioactive aerosols, the dosimetric models of the International Commission on Radiological Protection (ICRP) provide dose coefficients, retention and excretion functions. Unknown date or dates of intake is the major source of uncertainty in dose assessment during routine monitoring of nuclear workers. The two assumptions commonly made in dose assessment from an unknown time pattern of intake have been tested experimentally with a model of repeated inhalation by rats. The hypothetical intake derived from lung measurement was relatively reliable under the two hypotheses. The hypothetical intake derived from excreta measurement depended on the choice of hypothesis and on the real time pattern of intake

Alteration of mouse oocyte quality after a subchronic exposure to depleted Uranium

Gametes and embryo tissues are known to represent a sensitive target to environmental toxicants exposure. Oocyte quality can impact subsequent developmental competence, pregnancy course and even adult health. The major health concern from depleted uranium (DU) is mainly centred on its chemotoxic properties as a heavy metal. Little attention was paid to the impact of uranium on female gamete quality. The aim of this research was to evaluate the effect of DU on mouse oocyte quality after 49 days of subchronic contamination in drinking water and to correlate the observed effects with the amount of DU accumulated in organs. Four different DU concentrations were investigated: 0 (control), 10 (DU10), 20 (DU20) and 40 mg L-1 (DU40). DU did not influence the intensity of ovulation but affected oocyte quality. The proportion of healthy oocytes was reduced by half (P < 0.001) from 20 mg L-1 compared with control group (0.537; 0.497; 0.282 and 0.239 in control, DU10, DU20 and DU40 groups respectively) whereas no accumulation of DU was recorded in the ovaries whatever the dose tested. Abnormal perivitelline space (P < 0.001) or absence of the 1st polar body (P < 0.001) was identified as the main characteristic of DU impact. In the context of this study, the NOAEL for oocyte quality was determined at 10 mg L-1 in drinking water (1.9 mg kg-1 day-1). An increase in the dose of contamination over 20 mg L-1 did not amplify the proportion of oocytes contracting a specific alteration but conducted to a diversification in oocytes abnormalities. Further investigations are necessary to correlate morphologic assessment of female gamete with its developmental competence. © 2008 Elsevier Inc. All rights reserved

The effect of repeated inhalation on the distribution of uranium in rats

For the assessment of doses after inhalation of airborne uranium compounds by workers, the International Commission on Radiological Protection (ICRP) developed compartmental models that are used to calculate reference dose coefficients and retention and excretion functions. It is assumed that each acute intake has no effect on the biokinetics of later intakes. Consequently, retention and excretion after multiple or chronic exposure are predicted using the same models as after acute exposure. This assumption was tested here on rats exposed to repeated inhalation of uranium dioxide (UO 2 ). First, excretion and organ retention were determined after a single inhalation of UO 2 . The follow-up of incorporated activity was used to design a biokinetic model for uranium inhaled by rats. Second, the biokinetics of uranium were monitored in two experiments of repeated inhalations of uranium dioxide under different intake patterns. For these two experiments, the organs' retention and excretion after repeated UO 2 inhalation were predicted using the biokinetic model and compared to the experimental measurement. Under the two sets of experimental conditions considered, the prediction of the biokinetic model based on acute exposure data was consistent with the biokinetics observed after repeated UO 2 inhalations, with the possible exception of retention in the skeleton. Copyright© Taylor & Francis Group, LLC

Etude de l'exposition industrielle à des aérosols d'uranium dans le procédé d'enrichissement par laser. Méthodes et résultats

Le développement en France d'un nouveau procédé d'enrichissement par laser de l'uranium nous a conduits à étudier en situation industrielle les risques radiotoxiques liés à la formation d'un aérosol de type UO2+Umétal. Le but de ce travail est de déterminer pour ce mélange d'oxydes d'uranium les paramètres physico-chimiques et biocinétiques spécifiques à ce composé et nécessaires ultérieurement pour le calcul de dose, ceci en fonction du nouveau modèle pulmonaire décrit par la CIPR 66. Les résultats concernant les mesures de diamètre aérodynamique médian en activité (DAMA) donnent des valeurs comprises entre 5,2 et 10 µm avec jusqu'à 20 % de particules inférieures à 1 µm, tandis que les concentrations au poste de travail varient de 1,8 à 125 Bq m-3 et le calcul des périodes biologiques conduit à 48 j pour les tests de dissolution in vitro et à 77 j pour les expériences d'inhalation in vivo, les valeurs de taux de dissolution obtenues permettent d'affirmer que ce composé est de type W suivant la classification de la CIPR 30 et de type M suivant la CIPR 66

Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats

Depleted uranium (DU) is a radioactive heavy metal coming from the nuclear industry and used in numerous military applications. Uranium inhalation can lead to the development of fibrosis and neoplasia in the lungs. As little is known concerning the molecular processes leading to these pathological effects, some of the events in terms of genotoxicity and inflammation were investigated in rats exposed to DU by inhalation. Our results show that exposure to DU by inhalation resulted in DNA strand breaks in broncho-alveolar lavage (BAL) cells and in increase of inflammatory cytokine expression and production of hydroperoxides in lung tissue suggesting that the DNA damage was in part a consequence of the inflammatory processes and oxidative stress. The effects seemed to be linked to the doses, were independent of the solubility of uranium compounds and correlating with the type of inhalation. Repeated inhalations seemed to induce an effect of potentiation in BAL cells and also in kidney cells. Comet assay in neutral conditions revealed that DNA damage in BAL cells was composed partly by double strands breaks suggesting that radiation could contribute to DU genotoxic effects in vivo. All these in vivo results contribute to a better understanding of the pathological effect of DU inhalation. © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved

Distribution and genotoxic effects after successive exposure to different uranium oxide particles inhaled by rats

In nuclear fuel cycle facilities, workers may inhale airborne uranium compounds that lead to internal contamination, with various exposure scenarios depending on the workplace. These exposures can be chronic, repeated, or acute, and can involve many different compounds. The effect of uranium after multiple scenarios of exposure is unknown. The aim of this study, therefore, was to investigate the genotoxic and biokinetics consequences of exposure to depleted insoluble uranium dioxide (UO 2 ) by repeated or acute inhalation on subsequent acute inhalation of moderately soluble uranium peroxide (UO 4 ) in rats. The results show that UO 2 repeated preexposure by inhalation increases the genotoxic effects of UO 4 inhalation, assessed by comet assay, in different cell types, when UO 4 exposure alone has no effect. At the same time, the study of UO 4 bioaccumulation showed that the UO 4 biokinetics in the kidneys, gastrointestinal tract, and excreta, but not in the lungs, were slightly modified by previous UO 2 exposures. All these results show that both genotoxic and biokinetics effects of uranium may depend on preexposure and that repeated exposure induces a potentiation effect compared with acute exposure. Copyright © Informa Healthcare

Chronic exposure to uranium leads to iron accumulation in rat kidney cells

After it is incorporated into the body, uranium accumulates in bone and kidney and is a nephrotoxin. Although acute or short-term uranium exposures are well documented, there is a lack of information about the effects of chronic exposure to low levels of uranium on both occupationally exposed people and the general public. The objective of this study was to identify the distribution and chemical form of uranium in kidneys of rats chronically exposed to uranium in drinking water (40 mg uranium liter-1). Rats were killed humanely 6, 9, 12 and 18 months after the beginning of exposure. Kidneys were dissected out and prepared for optical and electron microscope analysis and energy dispersive X-ray (XEDS) or electron energy loss spectrometry (EELS). Microscopic analysis showed that proximal tubule cells from contaminated rats had increased numbers of vesicles containing dense granular inclusions. These inclusions were composed of clusters of small granules and increased in number with the exposure duration. Using XEDS and EELS, these characteristic granules were identified as iron oxides. Uranium was found to be present as a trace element but was never associated with the iron granules. These results suggested that the mechanisms of iron homeostasis in kidney could be affected by chronic uranium exposure. © 2007 by Radiation Research Society

La dosimétrie cytogénétique de l'accident d'irradiation

Lors d'une suspicion d'exposition accidentelle aux rayonnements ionisants, la détermination de la dose reçue au moyen de paramètres biologiques est une part importante de la stratégie thérapeutique, en complément des signes cliniques et de la dosimétrie physique. Le dénombrement des aberrations chromosomiques instables dans les lymphocytes du sang périphérique est aujourd'hui la méthode de référence. La préparation des échantillons biologiques dépend cependant du but à atteindre, de l'expertise précise de suspicions d'irradiations ou du tri rapide en cas d'accident de grande envergure. Une adaptation peut être nécessaire s'il s'agit d'irradiation hétérogène ou ancienne. Malgré cette robustesse et ces adaptations, la cytogénétique conventionnelle reste une technique lourde, longue, réservée à du personnel spécialisé. Le dénombrement des micronoyaux dans les lymphocytes binucléés peut constituer une alternative, apparemment plus facile et plus simple que le test des dicentriques. À partir de l'expérience acquise par l'IPSN ces dernières années sur l'expertise des suspicions d'irradiation, ce papier a pour but de dresser un bilan technique quoique succinct de ces différentes approches telles que nous les avons adaptées aux suspicions d'irradiation récente