Utilisation des poissons pour évaluer les effets biologiques des contaminants dans l’estuaire du Saint-Laurent et le fjord du Saguenay

Les organismes aquatiques de l’estuaire du Saint-Laurent (ESL) et du fjord du Saguenay (FS) sont exposés à des mélanges complexes de composés toxiques pouvant avoir un impact sur les populations, seuls ou en interaction avec d’autres facteurs environnementaux. L’objectif de cet article est de résumer l’information sur les effets biologiques des contaminants dans l’ESL et le FS obtenue à l’aide de poissons sentinelles. Trois études de cas démontrent la complémentarité de l’information obtenue avec différentes espèces. Les études sur l’anguille d’Amérique (Anguilla rostrata) montrent comment des poissons migrateurs peuvent être un vecteur important de contamination pour les prédateurs de haut niveau trophique de l’ESL. Des lésions prénéoplasiques au foie chez les anguilles en migration, probablement liées à une exposition aux hydrocarbures aromatiques polycycliques (HAP) sur leurs aires de croissance, sont un exemple d’effet à long terme de contaminants qui ne persistent pas dans les tissus des poissons. La présence d’adduits à l’ADN a été démontrée chez les poulamons atlantiques (Microgadus tomcod) résidents dans l’ESL et permet de comparer les niveaux d’exposition aux HAP génotoxiques entre l’ESL et d’autres estuaires de la côte Atlantique. Les études sur le poulamon ont aussi révélé une interaction entre leur période de jeûne hivernal et les produits organiques persistants (POP) menant à une augmentation transitoire des concentrations de POP dans le foie et à une dysfonction hépatique. Des échantillonnages sur le terrain, couplés à des expositions en cages in situ et à des expériences en laboratoire, ont permis de mettre évidence chez des plies canadiennes (Hipoglossoides platessoides) exposées à des sédiments contaminés de la baie des Anglais, des altérations immunitaires causant une augmentation de la susceptibilité aux maladies infectieuses. Les futures études devraient poursuivre le développement de biomarqueurs pour différents groupes de contaminants et les utiliser chez des espèces de poissons clés, à des stades sensibles de leur cycle de vie, en combinant différentes approches expérimentales multistresseurs à des études de surveillance sur le terrain.Aquatic organisms in the St. Lawrence Estuary (SLE) and the Saguenay Fjord (SF) are exposed to complex mixtures of toxic compounds which can have deleterious impacts on populations, alone or in combination with other environmental factors. The purpose of this paper is to summarize information about biological effects of contaminants in the SLE and SF obtained using sentinel fish species. Three case studies demonstrate the complementary nature of the information acquired using different sentinel species. Studies in American eel (Anguilla rostrata) show how migratory fish can be an important vector of contamination for high level predators in the SLE. Preneoplastic liver lesions in migrating eels, likely related to an exposure to polycyclic aromatic hydrocarbons (PAHs) in their growing areas, are an example of a long-term effect of contaminants which do not persist in fish tissues. DNA adducts were detected in resident SLE Atlantic tomcod (Microgadus tomcod) and can be used to compare the level of exposure to genotoxic PAHs between the SLE and other estuaries of the Atlantic coast. Studies in tomcod have also revealed an interaction between their winter fasting period and persistent organic compounds (POPs) leading to a transitory increase in concentrations of POPs in the liver and to hepatic dysfunction. Field samplings in association to in situ cage exposures and laboratory experiments have been used in American plaice (Hipoglossoides platessoides) exposed to contaminated sediments from Baie des Anglais, to demonstrate immune alterations causing increased susceptibility to infectious diseases. Future studies on biological effects of contaminants in fish in the SLE and SF should pursue the development of biomarkers for different groups of contaminants, and use them in key fish species, sampled at critical stages of their life cycle, in studies combining different multistressors experimental approaches to field monitoring

Reply to Lipworth et al.

We thank Dr. Lipworth and colleagues for their interest in our work published recently in the Journal (1). They rightly point out that the biology of asthma attacks is more complex than blood eosinophils alone and that corticosteroids have a wide range of other potentially relevant antiinflammatory effects. However, local treatment with inhaled corticosteroids (ICS) is usually the mainstay of patients with frequent eosinophilic exacerbations, and therefore in the great majority of patients, the key question is what oral corticosteroids (OCS) add to ICS in an acute attack (2) and whether this effect is seen with benralizumab. We suggest that depletion of circulating eosinophils is the only effect OCS are likely to have that are not shared with ICS (3)

Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design

We found that spadin, a natural peptide derived from sortilin, blocks the mouse TREK-1 channel and might be an efficient and fast-acting antidepressant

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Morphometrics and processing yield of Cucumaria frondosa (Holothuroidea) from the St. Lawrence Estuary, Canada.

Sea cucumber Cucumaria frondosa have highly variable whole body mass and length, and are usually sold to Asian markets as dried gutted body wall. Understanding the relation between size and yield of dry product is essential for resource conservation and for economic purposes. In this study, stock-specific mass and length recovery rates were estimated for C. frondosa captured by dredging or diving at various depths and seasons on the South shore of the St. Lawrence Estuary, along Gaspé Peninsula, and processed in a commercial plant. The processing yield in dry product mass per sea cucumber was more than 1.5 times larger for sea cucumbers collected at 26-47 m depth compared to those collected at 9-16 m depth. Within each strata, there was little variation in the processed body mass, seasonally or spatially. Recovery rates based on gutted mass for this stock (13.4─14.5%) varied little among depths and seasons, despite observed seasonal and bathymetric variation in reproductive status. In contrast, recovery rates based on whole body mass and length were highly variable both seasonally and spatially. Stress related to dredging or post-capture handling induced important variable body contraction and water content, leading to variation in body length, mass and shape of sea cucumbers having the same processed body mass. Gutted mass was the best metric to predict processed body mass and to estimate size whereas whole body length was the least reliable. New stock-specific information on variability of body mass, length, and recovery rates induced by capture, and on seasonal and bathymetric variation in reproductive status and processing yields will be used for the design of future stock assessment surveys, and for stock conservation

A multibiomarker approach on the Atlantic tomcod (Microgadus tomcod) in the St. Lawrence Estuary.

This work was conducted in the environmental immunotoxicology laboratory at Institut Armand Frappier (IAF-INRS). Financial support has been provided by the Canada Research Chair in Environmental Immunotoxicology (Dr. Michel Fournier) and Collège Doctoral International de l'Université européenne de Bretagne. This study was also supported by the INTERREG IV program (DIESE): 50 % of the Ph.D. grant was obtained by the first author, for the development of immune markers in ecotoxicology.International audienceA multibiomarker approach was developed on juvenile Atlantic tomcod (Microgadus tomcod) to evaluate the pertinence of this approach for low-cost screening assessment of the environmental quality of various coastal sites within estuaries. Several biometric indices and biomarkers (ethoxyresorufin-O-deethylase (EROD) activity, metallothionein concentration, and immune responses) were investigated on immature and maturing tomcods (≤ 31 months) collected in four environmentally contrasted sites in the St. Lawrence Estuary (SLE). Simultaneous examination of various age classes provides the opportunity to detect short-term responses in sensitive young-of-the-year fish (e.g., EROD induction) and longer-time effects associated with chronic exposure and bioaccumulation (e.g., metallothionein induction). Principal component analysis was helpful to discriminate between responses possibly related to contaminant exposure (EROD, metallothionein) and responses that could be affected by upstream-downstream gradient (immune response, biometric indices). Measurement of a battery of biomarkers in young tomcods at several sites along the shore of the SLE is a low-cost screening investigation useful to identify hot spots requiring further investigation with chemical analysis and additional reference sites

Relative potency of PCB126 to TCDD for sublethal embryotoxicity in the mummichog (Fundulus heteroclitus)

International audienceThe relative potency (ReP) of 3,3',4,4',5-pentachlorobiphenyl (PCB126) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for sublethal responses was assessed in Fundulus heteroclitus embryos. Eggs were treated with intravitelline injections of graded sublethal doses of PCB126 (312-5000 pg g(-1) wet weight, ww) or TCDD (5-1280 pg g(-1) ww). At 16 days post-fertilization (DPF), craniofacial deformities were observed in larvae hatched from eggs treated with the two highest doses of PCB126 (2500-5000 pg g(-1) ww). Both compounds caused a dose-responsive reduction of larval growth and prey capture ability (at ≥1250 pg g(-1) ww), and induction of ethoxyresorufin-O-deethylase (EROD) activity (at ≥80 pg g(-1) ww). The dose-response relationships for EROD activity for PCB126 and TCDD had similar slopes and the ReP of PCB126 to TCDD for EROD activity was estimated at 0.71. This is 140-fold higher than the World Health Organization (WHO) TCDD equivalency factor (TEF) of PCB126 for fish (0.005), which is based on rainbow trout (Oncorhynchus mykiss) embryolethality data. The slope of the dose-response relationship for prey capture ability for PCB126 was steeper than for TCDD, suggesting different mechanisms of action. Expression levels of several genes were also studied by quantitative real-time polymerase chain reaction (qPCR) following exposure to single doses of TCDD or PCB126 (1280 and 1250 pg g(-1) ww, respectively) causing similar EROD induction. A different pattern of responses was observed between PCB126 and TCDD: PCB126 appeared to induce antioxidant responses by inducing sod2 expression, while TCDD did not. These results suggest that relative potencies are species-specific and that the current ReP for PCB126 underestimates its toxicity for some fish species. It is recommended to develop species-specific RePs for a variety of sublethal endpoints and at environmentally relevant doses

Early back-calculated size-at-age of Atlantic yellow eels sampled along ecological gradients in the Gironde and St. Lawrence hydrographical systems

An international sampling program investigating the causes of the decline of American eels (Anguilla rostrata) and European eels (Anguilla anguilla) in the St. Lawrence (Canada) and Gironde (France) rivers systems provided the opportunity to compare early growth of eels of each species among habitats using back-calculated sizeâ at-age from 1 to 5 years old. Our study supports previous studies showing that the early back-calculated lengths of A. anguilla were higher in downstream and more saline Gironde system habitats than in the upstream fluvial section, and provides a new indication that length at 1-year-old is twice higher than that reported 10 years earlier. However, our data contradict the current paradigm for A. rostrata by providing evidence that early size-at-age of eels from the upstream St. Lawrence system, most distant from the spawning area, exceeds those of eels sampled downstream, at less distant sites in the estuarine section. Overall these observations are consistent with the hypothesis that the observed spatial variations in early growth rate of yellow eels sampled in the St. Lawrence and Gironde systems are the consequence of processes occurring in the first year of age such as genetic selection and/or genetically-dependent habitat choice.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Longitudinal changes in sputum and blood inflammatory mediators during FeNO suppression testing

To explore whether exhaled nitric oxide (FeNO) non-suppression identifies corticosteroid resistance, we analysed inflammatory mediator changes during a FeNO suppression test with monitored high-intensity corticosteroid therapy. In linear mixed-effects models analysed over time, the 15 clinically-distinct ‘suppressors’ (i.e. ≥42% FeNO suppression) normalised asthma control questionnaire scores (mean±SD: 2.8±1.4 to 1.4±0.9, p<0.0001) and sputum eosinophil counts (median [IQR]: 29 [6-41] to 1 [1-5]%, p=0.0003) while significantly decreasing sputum prostaglandin D2 (254 [89-894] to 93 [49-209] pg/mL, p=0.004) and numerically decreasing other type-2 cytokine, chemokine and alarmin levels. In comparison, the 19 non-suppressors had persistent sputum eosinophilia (10 [1-67]% despite high-intensity therapy) with raised end-test inflammatory mediator levels (1.9 [0.9-2.8]-fold greater than suppressors). FeNO non-suppression during monitored treatment implies biological corticosteroid resistance