Effect of prochloraz fungicide on biotransformation enzymes and oxidative stress parameters in three-spined stickleback (Gasterosteus aculeatus L.)

International audienceThe aim of this study was to characterize biomarker responses in three-spined sticklebacks exposed to prochloraz (Pcz). For this purpose, adult sticklebacks were exposed for 2 weeks to prochloraz at 0, 10, 50, 100 and 500 mu g/L prior to one week of depuration in clean water. At days 7, 14 and 21, several hepatic biomarkers were measured including 7-ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), total glutathione (GSH) content and thiobarbituric acid reactive substances (TBARS). Pcz induced a transient increase of antioxidant enzymes and a depletion of glutathione content during the first 7 days of exposure. This study showed that EROD activity and antioxidants were disrupted in a transient manner. GST was rapidly induced in a dose-dependent manner and this induction was persistent and observed also after depuration. GST appeared as a valuable biomarker to assess the exposure to Pcz

Comparison of two reference systems for biomarker data analysis in a freshwater biomonitoring context

International audienceThe usefulness of fish biomarkers for freshwater biomonitoring is now well recognized, but they still pose several questions to ecotoxicology researchers. The present study, designed to assess the effects of a small city located in an agricultural river basin watershed on sticklebacks living in an adjacent river, underlines the importance of reference selection. Two reference systems were used to analyse responses of a set of biomarkers, including biotransformation enzymes, oxidative stress parameters, neurotoxicity and endocrine disruption end-points, measured in wild sticklebacks electrofished in a contaminated stream. The results showed that the investigated urban pressure disturbed CYP3A activity but also induced hepatic lipoperoxidation and circulating vitellogenine but this result is strongly influenced by the selected reference system. This work therefore demonstrates the need for further research to identify a robust reference system for stickleback biomarker analysis

Assessment of seasonal variability of biomarkers in three-spined stickleback (Gasterosteurs aculatus L) from a low contaminated stream : implication for environmental biomonitoring

International audienceIn this study, wild three-spined sticklebacks were sampled every six weeks, between April and October, in a low contaminated stream. For all fish, physiological indexes, such as condition factor, hepato-, gonado- and nephro-somatic index were calculated to determine fish condition and reproductive status. Moreover, a set of biomarkers including biotransformation enzymes, oxidative stress parameters, neurotoxicity and endocrine disruption markers was measured. The results allowed to determine biomarker variability due to fish gender or sampling season. For example, 7-ethoxyresorufin-O-deethylase activity, glutathione peroxidase as well as vitellogenin and spiggin exhibited strong gender differences. Conversely, lipoperoxidation and acethyleholinesterase activity were characterised by a lack of gender and seasonal variation, and can be considered as more robust parameters for a field application. The present work allowed to establish practical guideline for biomarker measurements in wild sticklebacks and to define a reference system which can be used to analyze variations in future monitoring studies

Brain aromatase (Cyp19a1b) is a highly sensitive gene to estrogens and xeno-estrogens

International audienceAromatase is the only enzyme responsible for the irreversible conversion of androgens into estrogens. Teleost fishes have two copies of the cyp19a1 gene that encode two isoforms of aromatase: cyp19a1a encodes ovarian aromatase, while the cyp19a1b gene encodes brain aromatase (aromatase B). We have shown that (i) aromatase B is strongly expressed in radial glial cells (RGC), that act as stem cells in mammals and fish and ii) the cyp19a1b gene is very sensitive to estrogens, through a mechanism that involves a well conserved ERE. This feature makes this gene an outstanding biomarker of xeno-estrogen exposures and we have developed and validated an in vivo assay allowing detection of estrogenic activity with a very high sensitivity. The in vivo assay is based on a transgenic zebrafish tg(cyp19a1b-GFP) line that expresses GFP in RGCs and we demonstrate the usefulness of the transgenic cyp19a1b-GFP as a reliable, sensitive and rapid in vivo estrogenic screening assay

Adverse effects in wild fish living downstream from pharmaceutical manufacture discharges

International audienceA set of biochemical and histological responses was measured in wild gudgeon collected upstream and downstream of urban and pharmaceutical manufacture effluents. These individual end-points were associated to fish assemblage characterisation. Responses of biotransformation enzymes, neurotoxicity and endocrine disruption biomarkers revealed contamination of investigated stream by a mixture of pollutants. Fish from sampled sites downstream of the industrial effluent exhibited also strong signs of endocrine disruption including vitellogenin induction, intersex and male-biased sex-ratio. These individual effects were associated to a decrease of density and a lack of sensitive fish species. This evidence supports the hypothesis that pharmaceutical compounds discharged in stream are involved in recorded endocrine disruption effects and fish population disturbances and threaten disappearance of resident fish species. Overall, this study gives argument for the utilisation of an effect-based monitoring approach to assess impacts of pharmaceutical manufacture discharges on wild fish populations

An individual-based model of Zebrafish population dynamics accounting for energy dynamics

International audienceDeveloping population dynamics models for zebrafish is crucial in order to extrapolate from toxicity data measured at the organism level to biological levels relevant to support and enhance ecological risk assessment. To achieve this, a dynamic energy budget for individual zebrafish (DEB model) was coupled to an individual based model of zebrafish population dynamics (IBM model). Next, we fitted the DEB model to new experimental data on zebra-fish growth and reproduction thus improving existing models. We further analysed the DEB-model and DEB-IBM using a sensitivity analysis. Finally, the predictions of the DEB-IBM were compared to existing observations on natural zebrafish populations and the predicted population dynamics are realistic. While our zebrafish DEB-IBM model can still be improved by acquiring new experimental data on the most uncertain processes (e.g. survival or feeding), it can already serve to predict the impact of compounds at the population level

Use and Outcomes Associated With Bridging During Anticoagulation Interruptions in Patients With Atrial Fibrillation: Findings From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)

BACKGROUND: Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. METHODS AND RESULTS: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P=0.0003) and mechanical valve replacements (9.6% versus 2.4%; P/=2 in 94% versus 95%; P=0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84;

Early Adoption of Dabigatran and Its Dosing in US Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation

Background: Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results: We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new‐onset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001). Conclusions: Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. Clinical Trial Registration URL: Clinicaltrials.gov. Unique identifier: NCT01165710

Changes in quality of life, cognition and functional status following catheter ablation of atrial fibrillation

Objective To investigate changes in quality of life (QoL), cognition and functional status according to arrhythmia recurrence after atrial fibrillation (AF) ablation. Methods We compared QoL, cognition and functional status in patients with recurrent atrial tachycardia (AT)/AF versus those without recurrent AT/AF in the AXAFA-AFNET 5 clinical trial. We also sought to identify factors associated with improvement in QoL and functional status following AF ablation by overall change scores with and without analysis of covariance (ANCOVA). Results Among 518 patients who underwent AF ablation, 154 (29.7%) experienced recurrent AT/AF at 3 months. Patients with recurrent AT/AF had higher mean CHA(2)DS(2)-VASc scores (2.8 vs 2.3, p Conclusions Patients without recurrent AT/AF appear to experience greater improvement in functional status but similar QoL as those with recurrent AT/AF after AF ablation