MADOR: A NEW TOOL TO CALCULATE DECREASE OF EFFECTIVE DOSES IN HUMAN AFTER DTPA THERAPY

Abstract models have been developed to describe dissolution of Pu/Am/Cm after internal contamination by inhalation or wound, chelation of actinides by diethylene triamine penta acetic acid (DTPA) in different retention compartments and excretion of actinide-DTPA complexes. After coupling these models with those currently used for dose calculation, the modelling approach was assessed by fitting human data available in IDEAS database. Good fits were obtained for most studied cases, but further experimental studies are needed to validate some modelling hypotheses as well as the range of parameter values. From these first results, radioprotection tools are being developed: MAnagement of DOse Reduction after DTPA therapy

Etude de l'impact de l'imidaclopride sur les capacités d'apprentissage olfactif chez l'abeille domestique, Apis mellifera L. selon l'âge

* Inra Poitou-Charentes, ERIST, Route de Saintes BP 6, 86600 Lusignan (FRA) Diffusion du document : Inra Poitou-Charentes, ERIST, Route de Saintes BP 6, 86600 Lusignan (FRA) Diplôme : DEU

Reduction of peroxisome proliferation-activated receptor γ expression by γ-irradiation as a mechanism contributing to inflammatory response in rat colon: Modulation by the 5-aminosalicylic acid agonist

Radiation-induced intestinal injuries, including inflammation and immune response, remain a limiting factor in the effectiveness of pelvic radiotherapy and in the patient's quality of life during and after treatment. Peroxisome proliferation-activated receptor (PPAR) agonists are now emerging as therapeutic drugs for various inflammatory diseases that are characterized by impaired PPAR expression. The purpose of this study was to investigate the profile of PPAR expression in rat colonic mucosa 3 and 7 days after abdominal γ-irradiation (10 Gy). We tested whether irradiation-induced acute inflammatory response could be modulated pharmacologically with the antiinflammatory properties of 5-aminosalicylic acid (5-ASA) (250 mg/kg/day), which is a PPAR activator. Irradiation drastically reduced mRNA and protein levels of PPARα and -γ and of the heterodimer retinoid X receptor (RXR)α at 3 days postirradiation. 5-ASA treatment normalized both PPARγ and RXRα expression at 3 days postirradiation and PPARα at 7 days. By promoting PPAR expression and its nuclear translocation, 5-ASA interfered with the nuclear factor (NF)-κB pathway, both by reducing irradiation-induced NF-κB p65 translocation/activation and increasing the expression of nuclear factor-κB inhibitor (IκB) mRNA and protein. Therefore, 5-ASA prevents irradiation-induced inflammatory processes as well as expression of tumor necrosis factor α, monocyte chemotactic protein-1, inducible nitric-oxide synthase, and macrophage infiltration. In addition, 5-ASA restores the interferon γ/signal transducer and activator of transcription (STAT)-1 and STAT-3 concentrations that were impaired at 3 and 7 days postirradiation and are correlated with suppressor of cytokine signaling-3 repression. Collectively, these results indicate that PPAR agonists may be effective in the prevention of inflammatory processes and immune responses during and after pelvic radiotherapy. Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics

Caffeic acid phenethyl ester modifies the Th1/Th2 balance in ileal mucosa after γ-irradiation in the rat by modulating the cytokine pattern

Aim: To pharmacologically modulate Th polarization in the ileum exposed to ionizing radiation by using the immuno-modulatory/apoptotic properties of Caffeic Acid Phenethyl Ester (CAPE). Methods: Rats received CAPE (30 mg/kg) treatment ip 15 min prior to intestinal 10 Gy γ-irradiation and once a day for a 6 d period after irradiation. Expression of genes implicated in Th differentiation in ileal mucosa (IL-23/IL-12Rβ2), Th cytokine responses (IFN-γ, IL-2, IL-4, IL-13), Th migratory behaviour (CXCR3, CCR5, CCR4), Th signalling suppressors (SOCS1, SOCS3), transcription factor (T-Bet, GATA-3) and apoptosis (FasL/Fas, TNF/TNFR, XIAP, Bax, caspase-3) was analyzed by RT-PCR 6 h and 7 d post-irradiation. CD4+ and TUNEL positive cells were visualized by immunostaining. Results: The expression of Th1-related cytokine/chemokine receptors (IFN-γ, IL-2, CXCR3, CCR5) was repressed at 7 d post-irradiation while Th2 cell cytokine/chemokines (IL-4, IL-13, CCR4) were not repressed or even upregulated. The irradiation-induced Th2 profile was confirmed by the upregulation of both Th2-specific transcription factor GATA-3 and SOCS3. Although an apoptosis event occurred 6 h after 10 Gy of intestinal γ-irradiation, apoptotic mediator analysis showed a tendency to apoptotic resistance 7 d post-irradiation. CAPE amplified apoptotic events at 6h and normalized Bax/FasL expressions at 7 d. Conclusion: CAPE prevented the ileal Th2 immune response by modulating the irradiation-influenced cytokine environment and apoptosis. © 2006 The WJG Press. All rights reserved

Modélisation de la décorporation du Pu/am par le dtpa

A new tool has been developed to optimize DTPA efficacy as concerns reduction of effective dose after 239Pu wound. For example, the simulations show, for moderately soluble compounds (type M), a 1/3 decrease of effective dose is obtained after repeated early treatment (24 i.v. for 4 months), whereas a decrease by a factor 5 can be reached if treatments continue for 5 years at 2 week interval. By contrast, for poorly soluble compounds (type S), negligible efficacy is observed after early treatments, and a 3 time decrease of dose is obtained for treatments performed at 2 week interval for 50 years. Some of the hypotheses retained for modelling DTPA decorporation are validated from new experimental data published recently, and structure of a new model which can be applied both to Pu and Am is reported, taking into account urinary and faecal excretion, structure being suitable for different doses of DTPA and using various galenic forms. © 2009 EDP Sciences.Un nouvel outil a été développé pour optimiser l’efficacité des traitements par le DTPA après blessure, sur la base d’une réduction de la dose efficace engagée. Les simulations montrent, notamment, que pour du 239Pu modérément soluble (type M), des traitements précoces (24 i.v.) étalées sur 4 mois permettent une réduction d’un tiers de la dose, alors que leur prolongement sur 5 ans, avec un intervalle de 2 semaines, peut diminuer la dose d’un facteur 5. En revanche, pour des composés peu solubles (type S), l’efficacité des traitements précoces est négligeable et un gain dosimétrique d’un facteur 3 n’est atteint que pour des traitements effectués 2 fois par mois durant 50 ans. Certaines des hypothèses retenues pour la modélisation ont été validées par les résultats d’expérimentations animales récemment publiés. Enfin, la structure d’un nouveau modèle applicable à la fois au Pu et à l’Am est rapportée, structure tenant compte de la décorporation urinaire et fécale de ces actinides et qui pourrait être adapté à différentes posologies et formes galéniques de DTPA