Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinson's Disease

It is increasingly recognized that non-motor symptoms are a prominent feature of Parkinson's disease and in the case of cognitive deficits can precede onset of the characteristic motor symptoms. Here, we examine in 4 monkeys chronically treated with low doses of the neurotoxin MPTP the early and long-term alterations of rest-activity rhythms in relationship to the appearance of motor and cognitive symptoms.Behavioral activity recordings as well as motor and cognitive assessments were carried out continuously and in parallel before, during and for several months following MPTP-treatment (12–56 weeks). Cognitive abilities were assessed using a task that is dependent on the functional integrity of the fronto-striatal axis. Rest-activity cycles were monitored continuously using infrared movement detectors of locomotor activity. Motor impairment was evaluated using standardized scales for primates. Results show that MPTP treatment led to an immediate alteration (within one week) of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only became apparent 3 to 5 weeks after initiating chronic MPTP administration. In three of the four animals studied, clinical scores returned to control levels 5–7 weeks following cessation of MPTP treatment. In contrast, both cognitive deficits and chronobiological alterations persisted for many months. Levodopa treatment led to an improvement of cognitive performance but did not affect rest-activity rhythms in the two cases tested.Present results show that i) changes in the rest activity cycles constituted early detectable consequences of MPTP treatment and, along with cognitive alterations, characterize the presymptomatic stage; ii) following motor recovery there is a long-term persistence of non-motor symptoms that could reflect differential underlying compensatory mechanisms in these domains; iii) the progressive MPTP-monkey model of presymptomatic ongoing parkinsonism offers possibilities for in-depth studies of early non-motor symptoms including sleep alterations and cognitive deficits

LA MIGRATION DU PHOQUE A CAPUCHON ENTRE LES AIRES DE MISE BAS AU SUD-EST DU CANADA ET LES AIRES DE MUE AUX SUD-EST DU GROENLAND

BANYULS/MER-Observ.Océanol. (660162201) / SudocNANTES-Ecole Nat.Vétérinaire (441092302) / SudocSudocFranceF

Etude de l'effet d'un facteur neurotrophique dans un modèle primate de maladie de Parkinson

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Direct quantification of mitochondrial DNA and its 4.9-kb common deletion without DNA purification

International audienc

Acute emotional stress and high fat/high fructose diet modulate brain oxidative damage through NrF2 and uric acid in rats

International audienceStudies focusing on the interaction of dietary and acute emotional stress on oxidative stress in cortex frontal and in brain mitochondria are scarce. Dietary-induced insulin resistance, as observed in Western diets, has been associated with increased oxidative stress causing mitochondrial dysfunction. We hypothesized that acute emotional stress could be an aggravating factor by impacting redox status in cortex and brain mitochondria. Thus, the aim of the present study was to evaluate the combination of an insulin resistance inducing high-fat/high-fructose (HF/HFr) diet and acute emotional stress on brain oxidative stress in rats. We measured several oxidative stress parameters (carbonyls, FRAP, TBARS assays, GSH, GSSG, oxidized DNA, mRNA expression of redox proteins (Nrf2), and uric acid). The HF/HFr diet resulted in increased oxidative stress both in the brain mitochondria and in the frontal cortex and decreased expression of the Nrf2 gene. The emotional stress induced an oxidative response in plasma and in brain mitochondria of the control group. In the HF/HFr group it triggered an increase expression of the redox transcription factor Nrf2 and its downstream antioxidant genes. This suggests an improvement of the redox stress tolerance in response to an enhanced production of reactive oxygen species. Accordingly, a blunted oxidative effect on several markers was observed in plasma and brain of HF/HFr-stressed group. This was confirmed in a parallel study using lipopolysaccharide as a stress model. Beside the Nrf2 increase, the stress induced a stronger UA release in HF/HFr which could take a part in the redox stress

Ebola Virus RNA Stability in Human Blood and Urine in West Africa’s Environmental Conditions

We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa’s environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly

Towards Understanding Therapeutic Failures in Masquelet Surgery: First Evidence that Defective Induced Membrane Properties are Associated with Clinical Failures

International audienceThe two-stage Masquelet induced-membrane technique (IMT) consists of cement spacer-driven membrane induction followed by an autologous cancellous bone implantation in this membrane to promote large bone defect repairs. For the first time, this study aims at correlating IMT failures with physiological alterations of the induced membrane (IM) in patients. For this purpose, we compared various histological, immunohistochemical and gene expression parameters obtained from IM collected in patients categorized lately as successfully (Responders; n = 8) or unsuccessfully (Non-responders; n = 3) treated with the Masquelet technique (6 month clinical and radiologic post-surgery follow-up). While angiogenesis or macrophage distribution pattern remained unmodified in non-responder IM as compared to responder IM, we evidenced an absence of mesenchymal stem cells and reduced density of fibroblast-like cells in non-responder IM. Furthermore, non-responder IM exhibited altered extracellular matrix (ECM) remodeling parameters such as a lower expression ratio of metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinases (TIMP-1) mRNA as well as an important collagen overexpression as shown by picrosirius red staining. In summary, this study is the first to report evidence that IMT failure can be related to defective IM properties while underlining the importance of ECM remodeling parameters, particularly the MMP-9/TIMP-1 gene expression ratio, as early predictive biomarkers of the IMT outcome regardless of the type of bone, fracture or patient characteristics

La fonction de sensibilite aux contrastes sous stimulation vestibulaire

SIGLECNRS RP 174 (223) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Corticostriatopallidal Neuroprotection by Adenovirus-Mediated Ciliary Neurotrophic Factor Gene Transfer in a Rat Model of Progressive Striatal Degeneration

International audienceCiliary neurotrophic factor (CNTF) is a potent protective factor for striatal neurons in animal models of Huntington's disease (HD). Clinical application of this potential therapeutic still requires the design and optimization of delivery systems. In the case of HD, spatial spread in the vast volume occupied by the striatum and long-term delivery of the factor are particular challenges for these systems. We explored the potential of adenovirus-mediated gene transfer to fulfill these requirements by studying the functional and anatomical effects of single-site striatal delivery of CNTF recombinant vectors in a rat model of HD. In an initial series of experiments, unilateral injections of CNTF adenovirus were performed in rats 10, 30, or 90 d before a 5 d neurotoxic treatment with systemic 3-nitropropionic acid (3NP). Preservation of striatal neurons was observed at all time points, demonstrating temporally extended neuroprotective effects of the CNTF adenovirus. In a second series of experiments , bilateral injections of CNTF adenovirus were performed in the medial aspect of the striatum 10 d before starting 3NP intoxication. Despite placement of the CNTF-producing vector outside the lateral striatal area susceptible to lesion, massive protection of corticostriatopallidal circuits was observed, associated with significant behavioral benefits. This spatial spread of neuroprotection is discussed with reference to the retrograde transport of the adenovirus vector and the anterograde transport of the transgenic CNTF. Overall, adenovirus-mediated CNTF gene transfer appears to be a potentially useful delivery system for widespread, long-term circuit neuroprotection in HD patients