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Beta-N-Methylamino-L-Alanine: LC-MS/MS Optimization, Screening of Cyanobacterial Strains and Occurrence in Shellfish from Thau, a French Mediterranean Lagoon ArchiMer
Reveillon, Damien; Abadie, Eric; Sechet, Veronique; Brient, Luc; Savar, Veronique; Bardouil, Michele; Hess, Philipp; Amzil, Zouher.
beta-N-methylamino-L-alanine (BMAA) is a neurotoxic non-protein amino acid suggested to be involved in neurodegenerative diseases. It was reported to be produced by cyanobacteria, but also found in edible aquatic organisms, thus raising concern of a widespread human exposure. However, the chemical analysis of BMAA and its isomers are controversial, mainly due to the lack of selectivity of the analytical methods. Using factorial design, we have optimized the chromatographic separation of underivatized analogues by a hydrophilic interaction chromatography coupled to tandem mass spectrometry (HILIC-MS/MS) method. A combination of an effective solid phase extraction (SPE) clean-up, appropriate chromatographic resolution and the use of specific mass spectral...
Tipo: Text Palavras-chave: Cyanotoxins; BMAA; DAB; AEG; HILIC-MS/MS; Cyanobacteria; Bivalve mollusks; French Mediterranean.
Ano: 2014 URL: http://archimer.ifremer.fr/doc/00245/35579/34112.pdf
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Comparing diatom and Alexandrium catenella/tamarense blooms in Thau lagoon: Importance of dissolved organic nitrogen in seasonally N-limited systems ArchiMer
Collos, Yves; Jauzein, Cecile; Ratmaya, Widya; Souchu, Philippe; Abadie, Eric; Vaquer, André.
Diatom blooms in Thau lagoon are always related to rain events leading to inputs of inorganic nutrients such as phosphate, ammonium and nitrate through the watershed with time lags of about 1 week. In contrast, blooms of Alexandrium catenella/tamarense can occur following periods of 3 weeks without precipitation and no significant input of conventional nutrients such as nitrate and phosphate. Field results also indicate a significant drop (from 22–25 to 15–16 μM over 3 days) in dissolved organic nitrogen (DON) at the bloom peak, as well as a significant inverse relationship between A. catenella/tamarense cell density and DON concentrations that is not apparent for diatom blooms. Such dinoflagellate blooms are also associated with elevated (6–9 μM) ammonium...
Tipo: Text Palavras-chave: Alexandrium catenella/tamarense; Non classical blooms; Organic nitrogen; Ammonium; Growth rate.
Ano: 2014 URL: http://archimer.ifremer.fr/doc/00194/30488/29758.pdf
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Dietary BMAA Exposure in an Amyotrophic Lateral Sclerosis Cluster from Southern France ArchiMer
Masseret, Estelle; Banack, Sandra; Boumediene, Farid; Abadie, Eric; Brient, Luc; Pernet, Fabrice; Juntas-morales, Raoul; Pageot, Nicolas; Metcalf, James; Cox, Paul; Camu, William.
Background Dietary exposure to the cyanotoxin BMAA is suspected to be the cause of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and North America, this toxin has been identified in the marine environment of amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures have been described. Objectives We aimed at identifying cluster(s) of amyotrophic lateral sclerosis in the Hérault district, a coastal district from Southern France, and to search, in the identified area(s), for the existence of a potential dietary source of BMAA. Methods A spatio-temporal cluster analysis was performed in the district, considering all incident amyotrophic lateral sclerosis cases identified from 1994 to 2009 by our expert...
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Ano: 2013 URL: http://archimer.ifremer.fr/doc/00168/27941/26234.pdf
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Contribution of several nitrogen sources to growth of Alexandrium catenella during blooms in Thau lagoon, southern France ArchiMer
Collos, Y; Vaquer, A; Laabir, M; Abadie, Eric; Laugier, Thierry; Pastoureaud, Annie; Souchu, Philippe.
A monitoring program with a weekly sampling frequency over a 15-month period indicates that urea concentrations above a certain threshold level may trigger the blooms of Alexandrium catenella in Thau lagoon. However, urea concentrations were also sometimes related to ammonium and dissolved organic nitrogen concentrations, indicating that the role of urea may not be a direct one. An original approach is used to assess the relative contribution of several nitrogen sources (nitrate, nitrite, ammonium, urea) to growth of A. catenella by comparing nitrogen uptake rates to nitrogen-based growth rates estimated from dilution experiments during four blooms over a 4-year period (2001-2004) in Thau lagoon. Nitrate and nitrite contributed 0.1-14% and 0.1-5%...
Tipo: Text Palavras-chave: Uptake kinetics; Ammonium; Urea; Growth; Nitrogen; HAB; Alexandrium catenella.
Ano: 2007 URL: http://archimer.ifremer.fr/doc/2007/publication-6454.pdf
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Health risk assessment related to pinnatoxins in French shellfish ArchiMer
Arnich, Nathalie; Abadie, Eric; Delcourt, Nicolas; Fessard, Valérie; Fremy, Jean-marc; Hort, Vincent; Lagrange, Emmeline; Maignien, Thomas; Molgó, Jordi; Peyrat, Marie-bénédicte; Vernoux, Jean-paul; Mattei, César.
Pinnatoxins (PnTXs) are a group of emerging marine biotoxins produced by the benthic dinoflagellate Vulcanodinium rugosum, currently not regulated in Europe or in any other country in the world. In France, PnTXs were detected for the first time in 2011, in mussels from the Ingril lagoon (South of France, Mediterranean coast). Since then, analyses carried out in mussels from this lagoon have shown high concentrations of PnTXs for several months each year. PnTXs have also been detected, to a lesser extent, in mussels from other Mediterranean lagoons and on the Atlantic and Corsican coasts. In the French data, the main analog is PnTX G (low levels of PnTX A are also present in some samples). No cases of PnTXs poisoning in humans have been reported so far in...
Tipo: Text Palavras-chave: Pinnatoxins; Shellfish; Emerging marine biotoxins; Risk assessment.
Ano: 2020 URL: https://archimer.ifremer.fr/doc/00619/73105/72236.pdf
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A comparative analysis of Alexandrium catenella/tamarense blooms in Annaba Bay (Algeria) and Thau lagoon (France); phosphorus limitation as a trigger ArchiMer
Hadjadji, Imene; Frehi, Hocine; Ayada, Lembarek; Abadie, Eric; Collos, Yves.
Environmental conditions ultimately leading to blooms of the toxic dinoflagellate Alexandrium catenella/tamarense were investigated at two Mediterranean sites (Annaba Bay, Algeria and Thau lagoon, France). Three years were examined in details: 1992 (a pre-Alexandrium period), 2002 (a year with the first bloom in Annaba) and 2010 (a year with a major bloom in Annaba). Most conditions were similar, but ammonium concentrations were much higher in Annaba (up to 100 μM) than in Thau (up to 10 μM). First records of A. catenella/tamarense were in 1995 for Thau and 2002 for Annaba, and coincided with soluble reactive phosphorus (SRP) decreasing below a concentration of about 1 μM. No other environmental variable could be related to those blooms. Thus, it is likely...
Tipo: Text Palavras-chave: Alexandrium catenella/tamarense; Blooms; Algeria; France; Mediterranean.
Ano: 2014 URL: http://archimer.ifremer.fr/doc/00174/28574/26995.pdf
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Stratégie d’échantillonnage des lieux du REPHY Sanitaire et REPHYTOX pour la région Occitanie ArchiMer
Serais, Ophelie; Caillard, Elise; Abadie, Eric; Fiandrino, Annie.
Cette procédure a pour objet de décrire la stratégie d’échantillonnage des lieux de surveillance du REPHY Sanitaire et REPHYTOX dans la région Occitanie. Les logigrammes, présentés par secteur géographique, indiquent la logique opérationnelle à suivre entre les lieux de surveillance du REPHY et du REPHYTOX dans le cadre de la mise en oeuvre des stratégies de ces réseaux. Ces stratégies sont détaillées dans le document de procédure nationale REPHYTOX (version en vigueur) et plus particulièrement dans le paragraphe « STRATEGIE D'ECHANTILLONNAGE ».
Tipo: Text Palavras-chave: REPHY; REPHYTOX; Réseaux de surveillance; Toxines; Logigrammes; Occitanie.
Ano: 2021 URL: https://archimer.ifremer.fr/doc/00676/78856/81979.pdf
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A Feedback Mechanism to Control Apoptosis Occurs in the Digestive Gland of the Oyster Crassostrea gigas Exposed to the Paralytic Shellfish Toxins Producer Alexandrium catenella ArchiMer
Rolland, Jean-luc; Medhioub, Walid; Vergnes, Agnes; Abi-khalil, Celina; Savar, Veronique; Abadie, Eric; Masseret, Estelle; Amzil, Zouher; Laabir, Mohamed.
To better understand the effect of Paralytic Shellfish Toxins (PSTs) accumulation in the digestive gland of the Pacific oyster, Crassostrea gigas, we experimentally exposed individual oysters for 48 h to a PSTs producer, the dinoflagellate Alexandrium catenella. In comparison to the effect of the non-toxic Alexandrium tamarense, on the eight apoptotic related genes tested, Bax and BI.1 were significantly upregulated in oysters exposed 48 h to A. catenella. Among the five detoxification related genes tested, the expression of cytochrome P450 (CYP1A) was shown to be correlated with toxin concentration in the digestive gland of oysters exposed to the toxic dinoflagellate. Beside this, we observed a significant increase in ROS production, a decrease in...
Tipo: Text Palavras-chave: Shellfish; Toxin; Biomarker; Expression; Phytoplankton.
Ano: 2014 URL: http://archimer.ifremer.fr/doc/00225/33606/32003.pdf
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Isolation of 12 microsatellite markers following a pyrosequencing procedure and cross-priming in two invasive cryptic species, Alexandrium catenella (group IV) and A. tamarense (group III) (Dinophyceae) ArchiMer
Laporte, Martin; Shao, Zhaojun; Berrebi, Patrick; Laabir, Mohamed; Abadie, Eric; Faivre, Nicolas; Rieuvilleneuve, Fabien; Masseret, Estelle.
Alexandrium catenella (group IV) and Alexandrium tamarense (group III) (Dinophyceae) are two cryptic invasive phytoplankton species belonging to the A. tamarense species complex. Their worldwide spread is favored by the human activities, transportation and climate change. In order to describe their diversity in the Mediterranean Sea and understand their settlements and maintenances in this area, new microsatellite markers were developed based on Thau lagoon (France) samples of A. catenella and A. tamarense strains. In this study twelve new microsatellite markers are proposed. Five of these microsatellite markers show amplifications on A. tamarense and ten on A. catenella. Three of these 12 microsatellite markers allowed amplifications on both cryptic...
Tipo: Text Palavras-chave: Invasive species; Phytoplankton; Alexandrium; Dinophyceae; Microsatellite markers; Biogeography.
Ano: 2014 URL: http://archimer.ifremer.fr/doc/00189/30026/29398.pdf
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Pinnatoxins’ Deleterious Effects on Cholinergic Networks: From Experimental Models to Human Health ArchiMer
Delcourt, Nicolas; Lagrange, Emmeline; Abadie, Eric; Fessard, Valérie; Frémy, Jean-marc; Vernoux, Jean-paul; Peyrat, Marie-bénédicte; Maignien, Thomas; Arnich, Nathalie; Molgó, Jordi; Mattei, César.
Pinnatoxins (PnTXs) are emerging neurotoxins that were discovered about 30 years ago. They are solely produced by the marine dinoflagellate Vulcanodinium rugosum, and may be transferred into the food chain, as they have been found in various marine invertebrates, including bivalves. No human intoxication has been reported to date although acute toxicity was induced by PnTxs in rodents. LD50 values have been estimated for the different PnTXs through the oral route. At sublethal doses, all symptoms are reversible, and no neurological sequelae are visible. These symptoms are consistent with impairment of central and peripheral cholinergic network functions. In fact, PnTXs are high-affinity competitive antagonists of nicotinic acetylcholine receptors (nAChRs)....
Tipo: Text Palavras-chave: Pinnatoxins; Cyclic imines; Vulcanodinium rugosum; Nicotinic acetylcholine receptors; Acute neurotoxicity; Human intoxication; Myasthenia gravis.
Ano: 2019 URL: https://archimer.ifremer.fr/doc/00507/61883/65958.pdf
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Etude sanitaire de la zone n° 34.39 "Lotissements conchylicoles de la lagune de Thau" Groupe III. Département de l'Hérault ArchiMer
Marzin, Anahita; Crottier, Anais; Piquet, Jean-come; Abadie, Eric; Roque D'Orbcastel, Emmanuelle; Fiandrino, Annie.
L’étude de zone des lotissements conchylicoles de la lagune de Thau (34.39) a été menée, à la demande du Comité Régional de la Conchyliculture en Méditerranée et du préfet de l’Hérault, pour étudier la possibilité de sectoriser la zone de production en sous-zones, au regard du risque microbiologiques (REMI). Une étude de dossier a été réalisée afin de recenser les principales sources de contamination. Celles-ci sont essentiellement d’origine anthropique et impactent différemment les secteurs envisagés. Des prélèvements de coquillages du groupe 3 ont été réalisés de mai 2017 à mai 2018 avec une fréquence bimensuelle. Au regard des critères du règlement (CE) n° 854/2004, les résultats des analyses microbiologiques (indicateur Escherichia coli) ont permis...
Tipo: Text Palavras-chave: REMI; E. coli; Contamination bactériologique des coquillages; ROCCH; Contaminants chimiques; Milieu marin; Étude de zone; Lagune de Thau; Département de l’Hérault.
Ano: 2018 URL: http://archimer.ifremer.fr/doc/00459/57056/58965.pdf
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Troubles neurologiques liés à la consommation de coquillages : des intoxications au diagnostic encore peu connu ArchiMer
Sinno-tellier, Sandra; Delcourt, Nicolas; Abadie, Eric.
La consommation de coquillages bivalves (moules, huîtres...) peut être à l’origine de troubles neurologiques graves voire mortels, liés à l’accumulation dans la chair des mollusques de toxines naturelles dont les teneurs sont par ailleurs réglementées. En juin 2019, une intoxication spécifique liée à la consommation de moules contaminées par des toxines paralysantes a attiré l’attention de l’Anses et des Centres antipoison (CAP) sur une possible méconnaissance diagnostique des intoxications par des neurotoxines marines. Une étude rétrospective des cas d’intoxication par des coquillages enregistrés par les CAP de 2012 à 2019, et des données de surveillance réglementaire des zones de production conchylicoles, a permis d’identifier 15 cas probables...
Tipo: Text Palavras-chave: Sécurité des aliments; Neurotoxines; Intoxication; Centres antipoison; Coquillages; Conchyliculture.
Ano: 2021 URL: https://archimer.ifremer.fr/doc/00691/80279/83364.pdf
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Influence of Environmental Factors on the Paralytic Shellfish Toxin Content and Profile of Alexandrium catenella (Dinophyceae) Isolated from the Mediterranean Sea ArchiMer
Laabir, Mohamed; Collos, Yves; Masseret, Estelle; Grzebyk, Daniel; Abadie, Eric; Savar, Veronique; Sibat, Manoella; Amzil, Zouher.
Laboratory experiments were designed to study the toxin content and profile of the Alexandrium catenella strain ACT03 (isolated from Thau Lagoon, French Mediterranean) in response to abiotic environmental factors under nutrient-replete conditions. This dinoflagellate can produce various paralytic shellfish toxins with concentrations ranging from 2.9 to 50.3 fmol/cell. The toxin profile was characterized by carbamate toxins (GTX3, GTX4 and GTX5) and N-sulfocarbamoyl toxins (C1, C2, C3 and C4). C2 dominated at 12-18 degrees C, but only for salinities ranging from 10 to 25 psu, whereas GTX5 became dominant at temperatures ranging from 21 to 30 degrees C at almost all salinities. There was no significant variation in the cellular toxin amount from 18 degrees C...
Tipo: Text Palavras-chave: Alexandrium catenella; PSP toxins; Temperature; Salinity; Light.
Ano: 2013 URL: http://archimer.ifremer.fr/doc/00148/25969/24056.pdf
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Etude de Vulcanodinium rugosum (Dinoflagellé producteur de pinnatoxines) se développant dans la lagune méditerranéenne de l’Ingril ArchiMer
Abadie, Eric.
Harmful and / or toxic phytoplankton blooms impact for a long time marine ecosystems worldwide. These massive developments have an adverse effect on ecosystems and their exploitation. The lagoons of the region Languedoc-Roussillon are affected for decades. In addition to recurring health risks from Dinophysis (DSP toxins) and Alexandrium (PSP toxins), Vulcanodinium rugosum was identified in 2011 in the lagoon Ingril. This new species product pinnatoxins (neurotoxins). Through this thesis work, the biology of this new species (life cycle, growth condition, toxin production), its shellfish contamination capacity and geographic distribution in neighboring lagoons were studied on cultures in the laboratory and via environmental monitoring. The results of this...
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Ano: 2015 URL: https://archimer.ifremer.fr/doc/00473/58425/61002.pdf
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Pinnatoxines en lien avec l’espèce Vulcanodinium rugosum (II) ArchiMer
Mondeguer, Florence; Abadie, Eric; Herve, Fabienne; Bardouil, Michele; Sechet, Veronique; Raimbault, Virginie; Berteaux, Tom; Zendong, Suzie Zita; Palvadeau, Hubert; Amzil, Zouher; Hess, Philipp; Fessard, Valérie; Huguet, Antoine; Sosa, Silvio; Tubaro, Aurelia; Aráoz, Rómulo; Molgó, Jordi.
Pour tenter d’apporter des réponses aux questions soulevées par une précédente étude commanditée pour approfondir les connaissances sur Vulcanodinium rugosum, l’organisme producteur de la Pinnatoxine G (PnTX G) (Hess et al., 2012), les objectifs de cette nouvelle étude sont les suivants : - Elargissement de la zone initiale de prélèvement d’Ingril à toute la lagune méditerranéenne et mise à profit de l’augmentation du nombre d’échantillons pour vérifier l’impact de l’effet matrice dans l’analyse LC-SM/MS. - Mise en culture en masse de Vulcanodinium rugosum et - Conduite d’une expérience de contamination in vivo sur des moules pour vérifier l’accumulation de la PnTX-G et comprendre les mécanismes de la métabolisation des PnTXs et de ses composés associés.....
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Ano: 2015 URL: http://archimer.ifremer.fr/doc/00285/39635/38126.pdf
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Oyster Farming, Temperature, and Plankton Influence the Dynamics of Pathogenic Vibrios in the Thau Lagoon ArchiMer
Lopez-joven, Maria-carmen; Rolland, Jean-luc; Haffner, Philippe; Caro, Audrey; Roques, Cecile; Carre, Claire; Travers, Marie-agnes; Abadie, Eric; Laabir, Mohamed; Bonnet, Delphine; Destoumieux-garzon, Delphine.
Vibrio species have been associated with recurrent mass mortalities of juvenile oysters Crassostrea gigas threatening oyster farming worldwide. However, knowledge of the ecology of pathogens in affected oyster farming areas remains scarce. Specifically, there are no data regarding (i) the environmental reservoirs of Vibrio populations pathogenic to oysters, (ii) the environmental factors favoring their transmission, and (iii) the influence of oyster farming on the persistence of those pathogens. This knowledge gap limits our capacity to predict and mitigate disease occurrence. To address these issues, we monitored Vibrio species potentially pathogenic to C. gigas in 2013 and 2014 in the Thau Lagoon, a major oyster farming region in the coastal French...
Tipo: Text Palavras-chave: Vibrio; Shellfish farming; Bivalve mollusks; Mortality outbreak; Phytoplankton; Zooplankton.
Ano: 2018 URL: https://archimer.ifremer.fr/doc/00463/57479/59598.pdf
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Effect of Nitrate, Ammonium and Urea on Growth and Pinnatoxin G Production of Vulcanodinium rugosum ArchiMer
Abadie, Eric; Kaci, Lamia; Berteaux, Tom; Hess, Philipp; Sechet, Veronique; Masseret, Estelle; Rolland, Jean-luc; Laabir, Mohamed.
ulcanodinium rugosum, a recently described dinoflagellate species producing a potent neurotoxin (pinnatoxin G), has been identified in French Mediterranean lagoons and was responsible for recurrent episodes of shellfish toxicity detected by mouse bioassay. Until now, the biology and physiology of V. rugosum have not been fully investigated. We studied the growth characteristics and toxicity of a V. rugosum strain (IFR-VRU-01), isolated in the Ingril lagoon in June 2009 (North-Western French Mediterranean Sea). It was cultivated in Enriched Natural Sea Water (ENSW) with organic (urea) and inorganic (ammonium and nitrate) nitrogen, at a temperature of 25 °C and irradiance of 100 μmol/m2·s−1. Results showed that ammonium was assimilated by cells more rapidly...
Tipo: Text Palavras-chave: Vulcanodinium rugosum; Pinnatoxin G; Ingril lagoon; Growth; Nitrogen source.
Ano: 2015 URL: https://archimer.ifremer.fr/doc/00276/38748/37290.pdf
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REPHYTOX Leucate. Mise en forme des résultats sur la période 2014-2020 ArchiMer
Serais, Ophelie; Abadie, Eric; Hubert, Clarisse; Bellamy, Elise; Fiandrino, Annie; Lemoine, Maud; Neaud-masson, Nadine.
Ce rapport a été réalisé à la demande de la Direction Départementale de la Protection des Populations de l’Hérault (DDPP34). Les résultats en toxines lipophiles réglementées (Acide Okadaïque, Dinophysis toxines et Pectenotoxines uniquement) dans les moules et les huîtres prélevées au point « Parc Leucate 2 » dans le cadre du REPHYTOX, ainsi que les dénombrements du phytoplancton toxique du genre Dinophysis réalisés dans le cadre du REPHY dans la lagune de Leucate, sont présentés sur des graphiques permettant une visualisation temporelle des épisodes de contamination entre janvier 2014 et décembre 2020.
Tipo: Text Palavras-chave: REPHYTOX; REPHY; Leucate; Point Parc Leucate 2; Moules; Huîtres; Toxins lipophiles; Dinophysis; Graphiques; Période 2014-2020.
Ano: 2020 URL: https://archimer.ifremer.fr/doc/00662/77444/79099.pdf
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Contamination de l'etang de Thau par Alexandrium tamarense. Episode de novembre a decembre 1998 ArchiMer
Abadie, Eric; Zouher, Amzil; Belin, Catherine; Comps, Marie-annick; Elziere-papayanni, Panayota; Lassus, Patrick; Le Bec, Claude; Marcaillou-le Baut, Claire; Nezan, Elizabeth; Poggi, Robert.
A bloom of the toxic dinoflagellate Alexandrium tamarense was observed for the first time in Thau iagoon between November and December 1998. Maximum cell concentrations detected in shellfish farming areas (85 000 Cells/1) were high enough to make mussels and clams unsuitable for human consumption (max. 850 ug. STX eq.100 g'1) while toxic levels in oysters did not exceed, or even reach, the international public health threshold established for PSP toxins. This event, new to French Mediterranean waters, was investigated by both local and national veterinary services and by the Ifremer teams involved in the National Monitoring Network for Phytoplankton and Phycotoxines (Réphy). The chronological and operational description of the event was compared with data...
Tipo: Text Palavras-chave: Alexandrium; Monitoring; Toxic dinoflagellates; Thau lagoon; Alexandrium; Surveillance; Dinoflagellés toxiques; Etang de Thau.
Ano: 1999 URL: http://archimer.ifremer.fr/doc/1999/rapport-884.pdf
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Searching for a link between the L-BMAA neurotoxin and amyotrophic lateral sclerosis: a study protocol of the French BMAALS programme ArchiMer
Delzor, Aurelie; Couratier, Philippe; Boumediene, Farid; Nicol, Marie; Druet-cabanac, Michel; Paraf, Francois; Mejean, Annick; Ploux, Olivier; Leleu, Jean-philippe; Brient, Luc; Lengronne, Marion; Pichon, Valerie; Combes, Audrey; El Abdellaoui, Saida; Bonneterre, Vincent; Lagrange, Emmeline; Besson, Gerard; Bicout, Dominique J.; Boutonnat, Jean; Camu, William; Pageot, Nicolas; Juntas-morales, Raul; Rigau, Valerie; Masseret, Estelle; Abadie, Eric; Preux, Pierre-marie; Marin, Benoit.
Introduction: Amyotrophic lateral sclerosis (ALS) is the most common motor neurone disease. It occurs in two forms: (1) familial cases, for which several genes have been identified and (2) sporadic cases, for which various hypotheses have been formulated. Notably, the beta-N-methylamino-L-alanine (L-BMAA) toxin has been postulated to be involved in the occurrence of sporadic ALS. The objective of the French BMAALS programme is to study the putative link between L-BMAA and ALS. Methods and analysis: The programme covers the period from 1 January 2003 to 31 December 2011. Using multiple sources of ascertainment, all the incident ALS cases diagnosed during this period in the area under study (10 counties spread over three French regions) were collected....
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Ano: 2014 URL: https://archimer.ifremer.fr/doc/00443/55431/56952.pdf
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