Use of Biosensors as Alternatives to Current Regulatory Methods for Marine Biotoxins

Marine toxins are currently monitored by means of a bioassay that requires the use of many mice, which poses a technical and ethical problem in many countries. With the exception of domoic acid, there is a legal requirement for the presence of other toxins (yessotoxin, saxitoxin and analogs, okadaic acid and analogs, pectenotoxins and azaspiracids) in seafood to be controlled by bioassay, but other toxins, such as palytoxin, cyclic imines, ciguatera and tetrodotoxin are potentially present in European food and there are no legal requirements or technical approaches available to identify their presence. The need for alternative methods to the bioassay is clearly important, and biosensors have become in recent years a feasible alternative to animal sacrifice. This review will discuss the advantages and disadvantages of using biosensors as alternatives to animal assays for marine toxins, with particular focus on surface plasmon resonance (SPR) technology.

[1]  A. Turner,et al.  Immunosensor for okadaic acid using quartz crystal microbalance , 2002 .

[2]  C. K. Wong,et al.  Puffer fish poisoning. , 1995, Journal of accident & emergency medicine.

[3]  J. Vick,et al.  Toxicological evaluation of palytoxin in several animal species. , 1974, Toxicon : official journal of the International Society on Toxinology.

[4]  G. Ronzitti,et al.  Selective disruption of the E-cadherin–catenin system by an algal toxin , 2004, British Journal of Cancer.

[5]  M. Vieytes,et al.  Development of a F actin-based live-cell fluorimetric microplate assay for diarrhetic shellfish toxins. , 2003, Analytical biochemistry.

[6]  G. B. Elyakov,et al.  An enzyme linked immunosorbent assay for detecting palytoxin-producing bacteria , 2000, Russian Journal of Bioorganic Chemistry.

[7]  T. Yasumoto,et al.  A protein phosphatase 2A inhibition assay for a fast and sensitive assessment of okadaic acid contamination in mussels. , 1996, Toxicon : official journal of the International Society on Toxinology.

[8]  Balls Michael,et al.  The Validation of Alternative Test Methods , 1996 .

[9]  Christopher T Elliott,et al.  Immunobiosensor detection of domoic acid as a screening test in bivalve molluscs: comparison with liquid chromatography-based analysis. , 2006, Journal of AOAC International.

[10]  M. Sandvik,et al.  Antibodies with broad specificity to azaspiracids by use of synthetic haptens. , 2006, Journal of the American Chemical Society.

[11]  M. Adams,et al.  Neurotoxins: overview of an emerging research technology , 1994, Trends in Neurosciences.

[12]  R. Draisci,et al.  High levels of yessotoxin in mussels and presence of yessotoxin and homoyessotoxin in dinoflagellates of the Adriatic Sea. , 1999, Toxicon : official journal of the International Society on Toxinology.

[13]  C. Ménard,et al.  Quantitative determination of paralytic shellfish poisoning toxins in shellfish using prechromatographic oxidation and liquid chromatography with fluorescence detection: interlaboratory study. , 2004, Journal of AOAC International.

[14]  A. Gago-Martínez,et al.  Further improvements in the application of high-performance liquid chromatography, capillary electrophoresis and capillary electrochromatography to the analysis of algal toxins in the aquatic environment. , 2003, Journal of chromatography. A.

[15]  L. Fleming,et al.  Neurotoxic Shellfish Poisoning , 2008, Marine drugs.

[16]  M. Vieytes,et al.  Solid-phase radioreceptor assay for paralytic shellfish toxins. , 1993, Analytical biochemistry.

[17]  C. Y. Kao Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena. , 1966, Pharmacological reviews.

[18]  P. Vale Complex profiles of hydrophobic paralytic shellfish poisoning compounds in Gymnodinium catenatum identified by liquid chromatography with fluorescence detection and mass spectrometry. , 2008, Journal of chromatography. A.

[19]  W. Carmichael Seafood and Freshwater Toxins; Pharmacology, Physiology and Detection , 2002 .

[20]  Richard E. Moore,et al.  Palytoxin: A New Marine Toxin from a Coelenterate , 1971, Science.

[21]  M. Satake,et al.  Oral and intraperitoneal acute toxicity studies of yessotoxin and homoyessotoxins in mice. , 2003, Toxicon : official journal of the International Society on Toxinology.

[22]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[23]  J. Dunlop,et al.  Recombinant human voltage-gated skeletal muscle sodium channels are pharmacologically functional in planar lipid bilayers. , 2007, Biosensors & bioelectronics.

[24]  O. Wassermann,et al.  A method for the isolation of the caribbean palytoxin (C-PTX) from the coelenterate (zooanthid) Palythoa caribaeorum. , 1983, Toxicon : official journal of the International Society on Toxinology.

[25]  L. Fritz,et al.  Ultrastructure of two toxic marine dinoflagellates, Prorocentrum lima and Prorocentrum maculosum , 1993 .

[26]  T. Iwashita,et al.  Studies on palytoxins , 1985 .

[27]  J H Luong,et al.  Developments and applications of biosensors in food analysis. , 1997, Trends in biotechnology.

[28]  T. Birkbeck,et al.  Effect of Phosphate Concentration on Production of Tetrodotoxin by Alteromonas tetraodonis , 1993, Applied and environmental microbiology.

[29]  M. Vieytes,et al.  Effects of Azaspiracids 2 and 3 on intracellular cAMP, [Ca2+], and pH. , 2004, Chemical research in toxicology.

[30]  U. Sauer Animal vs. non-animal tests for the monitoring of marine biotoxins in the EU. , 2005, ALTEX.

[31]  R. Lewis,et al.  Lophozozymus pictor toxin: a fluorescent structural isomer of palytoxin. , 1995, Toxicon : official journal of the International Society on Toxinology.

[32]  J. Silke,et al.  Two analogs of azaspiracid isolated from mussels, Mytilus edulis, involved in human intoxication in Ireland. , 1999, Natural toxins (Print).

[33]  D. Baden,et al.  Specific antibodies directed against toxins of Ptychodiscus brevis (Florida's red tide dinoflagellate). , 1984, Toxicon : official journal of the International Society on Toxinology.

[34]  Paul Leonard,et al.  Antibody production, design and use for biosensor-based applications. , 2009, Seminars in cell & developmental biology.

[35]  Hugo A. Magaña,et al.  A historical assessment of Karenia brevis in the western Gulf of Mexico , 2003 .

[36]  T. Noguchi,et al.  TTX accumulation in pufferfish. , 2006, Comparative biochemistry and physiology. Part D, Genomics & proteomics.

[37]  G. Rossini,et al.  A slot blot procedure for the measurement of yessotoxins by a functional assay. , 2007, Toxicon : official journal of the International Society on Toxinology.

[38]  K. Nicolaou,et al.  Azaspiracid substituent at C1 is relevant to in vitro toxicity. , 2008, Chemical research in toxicology.

[39]  P. Thibault,et al.  Analysis of domoic acid isomers in seafood by capillary electrophoresis , 1997, Electrophoresis.

[40]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[41]  B. Thomson,et al.  Ion-spray mass spectrometry of marine neurotoxins. , 1989, Rapid communications in mass spectrometry : RCM.

[42]  M. Satake,et al.  Identification of Protoceratium reticulatum as the biogenetic origin of yessotoxin. , 1998, Natural toxins.

[43]  B. Gessner,et al.  Epidemiologic Impact of Toxic Episodes: Neurotoxic Toxins , 2008 .

[44]  D. Mountfort,et al.  Protein phosphatase inhibition assay adapted for determination of total DSP in contaminated mussels. , 2001, Toxicon : official journal of the International Society on Toxinology.

[45]  B. Espiña,et al.  Feasibility of gymnodimine and 13-desmethyl C spirolide detection by fluorescence polarization using a receptor-based assay in shellfish matrixes. , 2010, Analytica chimica acta.

[46]  C. Vale,et al.  Measurement of Algal Toxins in the Environment , 2009 .

[47]  P. Hess,et al.  Solid phase extraction for removal of matrix effects in lipophilic marine toxin analysis by liquid chromatography-tandem mass spectrometry , 2009, Analytical and bioanalytical chemistry.

[48]  J. Cravedi,et al.  SCIENTIFIC OPINION Marine biotoxins in shellfish - Domoic acid 1 Scientific Opinion of the Panel on Contaminants in the Food Chain , 2009 .

[49]  M. Loughran,et al.  Use of a channel biosensor for the assay of paralytic shellfish toxins. , 1998, Toxicon : official journal of the International Society on Toxinology.

[50]  F. V. Van Dolah,et al.  Marine Algal Toxins : Origins , Health Effects , and Their Increased Occurrence , 2006 .

[51]  T. Aune,et al.  Detection and identification of spirolides in norwegian shellfish and plankton. , 2005, Chemical research in toxicology.

[52]  A. Daranas,et al.  Yessotoxins, a Group of Marine Polyether Toxins: an Overview , 2008, Marine drugs.

[53]  M. Twiner,et al.  Extraction and analysis of lipophilic brevetoxins from the red tide dinoflagellate Karenia brevis. , 2007, Analytical biochemistry.

[54]  C. Montigny,et al.  Domoic acid, the alleged "mussel toxin," might produce its neurotoxic effect through kainate receptor activation: an electrophysiological study in the dorsal hippocampus. , 1989, Canadian journal of physiology and pharmacology.

[55]  G. Palleschi,et al.  Enzyme inhibition-based biosensors for food safety and environmental monitoring. , 2006, Biosensors & bioelectronics.

[56]  K. Nicolaou,et al.  Cell volume decrease as a link between azaspiracid-induced cytotoxicity and c-Jun-N-terminal kinase activation in cultured neurons. , 2010, Toxicological sciences : an official journal of the Society of Toxicology.

[57]  Bertold Hock,et al.  DEVELOPMENT OF MONOCLONAL ANTIBODIES TO DOMOIC ACID FOR THE DETECTION OF DOMOIC ACID IN BLUE MUSSEL (MYTILUS EDULIS) TISSUE BY ELISA , 2002 .

[58]  M. Quilliam,et al.  Analysis of domoic acid in shellfish by thin-layer chromatography. , 1998, Natural toxins.

[59]  R. Lewis,et al.  Identification of Caribbean ciguatoxins as the cause of an outbreak of fish poisoning among U.S. soldiers in Haiti. , 1997, Toxicon.

[60]  J. F. Lawrence,et al.  Quantitative determination of paralytic shellfish poisoning toxins in shellfish by using prechromatographic oxidation and liquid chromatography with fluorescence detection. , 2001, Journal of AOAC International.

[61]  G. Palleschi,et al.  A bienzyme electrochemical probe for flow injection analysis of okadaic acid based on protein phosphatase-2A inhibition: an optimization study. , 2009, Analytical biochemistry.

[62]  C. Dell’Aversano,et al.  Toxin profile of Alexandrium ostenfeldii (Dinophyceae) from the Northern Adriatic Sea revealed by liquid chromatography-mass spectrometry. , 2006, Toxicon : official journal of the International Society on Toxinology.

[63]  M. Vieytes,et al.  Detection of sodium channel activators by a rapid fluorimetric microplate assay. , 2004, Chemical research in toxicology.

[64]  L. Botana,et al.  Detection of gymnodimine-A and 13-desmethyl C spirolide phycotoxins by fluorescence polarization. , 2009, Analytical chemistry.

[65]  J F Lawrence,et al.  Liquid chromatographic determination of domoic acid in mussels, using AOAC paralytic shellfish poison extraction procedure: collaborative study. , 1991, Journal - Association of Official Analytical Chemists.

[66]  G. Tomaselli,et al.  A functional assay for paralytic shellfish toxins that uses recombinant sodium channels. , 2001, Toxicon : official journal of the International Society on Toxinology.

[67]  J. Vieites,et al.  Incidence of Marine Toxins on Industrial Activity , 2000 .

[68]  M. Poli,et al.  Prophylaxis and treatment with a monoclonal antibody of tetrodotoxin poisoning in mice. , 1995, Toxicon : official journal of the International Society on Toxinology.

[69]  G. Bignami A rapid and sensitive hemolysis neutralization assay for palytoxin. , 1993, Toxicon : official journal of the International Society on Toxinology.

[70]  K. Steidinger,et al.  A competitive ELISA to detect brevetoxins from Karenia brevis (formerly Gymnodinium breve) in seawater, shellfish, and mammalian body fluid. , 2002, Environmental health perspectives.

[71]  P. Hess,et al.  Confirmation by LC-MS/MS of azaspiracids in shellfish from the Portuguese north-western coast. , 2008, Toxicon : official journal of the International Society on Toxinology.

[72]  T. Yasumoto,et al.  Comparison of oral and intraperitoneal toxicity of yessotoxin towards mice. , 2002, Toxicon : official journal of the International Society on Toxinology.

[73]  T. Yasumoto,et al.  Fluorometric measurement of yessotoxins in shellfish by high-pressure liquid chromatography. , 1997, Bioscience, biotechnology, and biochemistry.

[74]  T. Yasumoto,et al.  Occurrence of a new type of shellfish poisoning in the Tohoku district. , 1978 .

[75]  J. Cravedi,et al.  SCIENTIFIC OPINION Marine biotoxins in shellfish - Pectenotoxin group 1 Scientific Opinion of the Panel on Contaminants in the Food chain , 2009 .

[76]  C. Miles,et al.  Yessotoxins in Norwegian blue mussels (Mytilus edulis): uptake from Protoceratium reticulatum, metabolism and depuration. , 2005, Toxicon : official journal of the International Society on Toxinology.

[77]  M. Quilliam The role of chromatography in the hunt for red tide toxins. , 2003, Journal of chromatography. A.

[78]  Antje J Baeumner,et al.  Biosensors for environmental pollutants and food contaminants , 2003, Analytical and bioanalytical chemistry.

[79]  M. Vieytes,et al.  Yessotoxin, a novel phycotoxin, activates phosphodiesterase activity. Effect of yessotoxin on cAMP levels in human lymphocytes. , 2003, Biochemical pharmacology.

[80]  M. Satake,et al.  Ubiquitous 'benign' alga emerges as the cause of shellfish contamination responsible for the human toxic syndrome, azaspiracid poisoning. , 2003, Toxicon : official journal of the International Society on Toxinology.

[81]  D. Baden,et al.  Radioimmunoassay for PbTx-2-type brevetoxins: epitope specificity of two anti-PbTx sera. , 1995, Journal of AOAC International.

[82]  Michael Thompson,et al.  Harmonized guidelines for single-laboratory validation of methods of analysis (IUPAC Technical Report) , 2002 .

[83]  R. Leblanc,et al.  Coumaryl crown ether based chemosensors: Selective detection of saxitoxin in the presence of sodium and potassium ions , 2002 .

[84]  Kao Cy TETRODOTOXIN, SAXITOXIN AND THEIR SIGNIFICANCE IN THE STUDY OF EXCITATION PHENOMENA , 1966 .

[85]  G. Eaglesham,et al.  Multiresidue method for determination of algal toxins in shellfish: single-laboratory validation and interlaboratory study. , 2005, Journal of AOAC International.

[86]  P. Hess,et al.  Discovery of new analogs of the marine biotoxin azaspiracid in blue mussels (Mytilus edulis) by ultra-performance liquid chromatography/tandem mass spectrometry. , 2008, Rapid communications in mass spectrometry : RCM.

[87]  G. Hallegraeff A review of harmful algal blooms and their apparent global increase , 1993 .

[88]  G. Guilbault,et al.  Immunosensor for the Determination of Okadaic Acid Based on Screen-Printed Electrode , 2003 .

[89]  G. Eaglesham,et al.  Emerging tropical diseases in Australia. Part 2. Ciguatera fish poisoning , 2010, Annals of tropical medicine and parasitology.

[90]  A. E. Greenberg,et al.  Laboratory procedures for the examination of seawater and shellfish , 1984 .

[91]  H. Fujiki,et al.  Tumor promotion by inhibitors of protein phosphatases 1 and 2A: the okadaic acid class of compounds. , 1993, Advances in cancer research.

[92]  Y. Hashimoto,et al.  Toxicity of the zoanthid Palythoa tuberculosa. , 1972, Toxicon : official journal of the International Society on Toxinology.

[93]  P. Guire,et al.  Development of Immunoassays for Paralytic Shellfish Poisoning: A Radioimmunoassay for Saxitoxin , 1984 .

[94]  T. Yasumoto,et al.  Suitability of the MTT-based cytotoxicity assay to detect okadaic acid contamination of mussels. , 1996, Toxicon : official journal of the International Society on Toxinology.

[95]  B. Sykes,et al.  A Molecular Basis for Different Interactions of Marine Toxins with Protein Phosphatase-1 , 1997, The Journal of Biological Chemistry.

[96]  T. Yasumoto,et al.  Fluorometric analysis of pectenotoxin-2 in microalgal samples by high performance liquid chromatography. , 1999, Natural toxins.

[97]  I. Rayment,et al.  A structural basis for regulation of actin polymerization by pectenotoxins. , 2007, Journal of molecular biology.

[98]  R. E. Gawley,et al.  Visible fluorescence chemosensor for saxitoxin. , 2007, The Journal of organic chemistry.

[99]  Natalia Vilariño,et al.  Assessment of specific binding proteins suitable for the detection of paralytic shellfish poisons using optical biosensor technology. , 2007, Analytical chemistry.

[100]  F. V. Dolah Diversity of Marine and Freshwater Algal Toxins , 2000 .

[101]  A. Takai,et al.  Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics. , 1988, The Biochemical journal.

[102]  M. Vieytes,et al.  A fluorimetric method based on changes in membrane potential for screening paralytic shellfish toxins in mussels. , 2001, Analytical biochemistry.

[103]  Y. Hokama,et al.  Development of an enzyme‐linked immunosorbent assay for the detection of ciguatoxin in fish tissue using chicken immunoglobulin Y , 2008, Journal of clinical laboratory analysis.

[104]  S. Bates,et al.  Pennate Diatom Nitzschia pungens as the Primary Source of Domoic Acid, a Toxin in Shellfish from Eastern Prince Edward Island, Canada , 1989 .

[105]  S. Fraga,et al.  Determination of diarrhetic shellfish toxins in various dinoflagellate species , 1989, Journal of Applied Phycology.

[106]  K. Janda,et al.  Monoclonal Antibodies with Orthogonal Azaspiracid Epitopes , 2009, Chembiochem : a European journal of chemical biology.

[107]  D. Stirling Survey of historical New Zealand shellfish samples for accumulation of gymnodimine , 2001 .

[108]  M. Amar,et al.  The marine phycotoxin gymnodimine targets muscular and neuronal nicotinic acetylcholine receptor subtypes with high affinity , 2008, Journal of neurochemistry.

[109]  N. Melchiorre,et al.  The Genoa 2005 outbreak. Determination of putative palytoxin in Mediterranean Ostreopsis ovata by a new liquid chromatography tandem mass spectrometry method. , 2006, Analytical chemistry.

[110]  W. Guida,et al.  Chemosensors for the marine toxin saxitoxin. , 2002, Journal of the American Chemical Society.

[111]  K. James,et al.  The first identification of azaspiracids in shellfish from France and Spain. , 2003, Toxicon : official journal of the International Society on Toxinology.

[112]  Philipp Hess,et al.  Development and single-laboratory validation of a pseudofunctional biosensor immunoassay for the detection of the okadaic acid group of toxins. , 2009, Analytical chemistry.

[113]  J. Diogène,et al.  Comparative study of the use of neuroblastoma cells (Neuro-2a) and neuroblastomaxglioma hybrid cells (NG108-15) for the toxic effect quantification of marine toxins. , 2008, Toxicon : official journal of the International Society on Toxinology.

[114]  Christophe A. Marquette,et al.  Semi-automated membrane based chemiluminescent immunosensor for flow injection analysis of okadaic acid in mussels , 1999 .

[115]  J. Molgó,et al.  Ciguatoxin enhances quantal transmitter release from frog motor nerve terminals , 1990, British journal of pharmacology.

[116]  J. Cooney,et al.  Identification of pectenotoxin-11 as 34S-hydroxypectenotoxin-2, a new pectenotoxin analogue in the toxic dinoflagellate Dinophysis acuta from New Zealand. , 2006, Chemical research in toxicology.

[117]  J. K. Sims,et al.  Pufferfish poisoning: emergency diagnosis and management of mild human tetrodotoxication. , 1986, Annals of emergency medicine.

[118]  M. Vieytes,et al.  Feasibility of using a surface plasmon resonance-based biosensor to detect and quantify yessotoxin. , 2008, Analytica chimica acta.

[119]  M. Satake,et al.  First evidence of an extensive northern European distribution of azaspiracid poisoning (AZP) toxins in shellfish. , 2002, Toxicon : official journal of the International Society on Toxinology.

[120]  W. Catterall,et al.  Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. , 2000, Biochimie.

[121]  M. Vieytes,et al.  Study of the interaction between different phosphodiesterases and yessotoxin using a resonant mirror biosensor. , 2006, Chemical research in toxicology.

[122]  James W Noah,et al.  New developments and emerging trends in high-throughput screening methods for lead compound identification , 2010 .

[123]  M. Vieytes,et al.  Azaspiracid-4 inhibits Ca2+ entry by stored operated channels in human T lymphocytes. , 2005, Biochemical pharmacology.

[124]  T. Birkbeck,et al.  A tissue culture assay for direct detection of sodium channel blocking toxins in bacterial culture supernates. , 1992, FEMS microbiology letters.

[125]  J. Kanchanapongkul,et al.  An epidemic of tetrodotoxin poisoning following ingestion of the horseshoe crab Carcinoscorpius rotundicauda. , 1995, The Southeast Asian journal of tropical medicine and public health.

[126]  Y. Hokama A rapid, simplified enzyme immunoassay stick test for the detection of ciguatoxin and related polyethers from fish tissues. , 1985, Toxicon : official journal of the International Society on Toxinology.

[127]  A. Cembella,et al.  Cyclic imine toxins: chemistry, biogeography, biosynthesis and pharmacology. , 2007 .

[128]  H. Oguri,et al.  Synthesis-based approach toward direct sandwich immunoassay for ciguatoxin CTX3C. , 2003, Journal of the American Chemical Society.

[129]  N. Matsumori,et al.  Surface plasmon resonance-based detection of ladder-shaped polyethers by inhibition detection method. , 2009, Bioorganic & medicinal chemistry letters.

[130]  N. Kulagina,et al.  Pharmacological effects of the marine toxins, brevetoxin and saxitoxin, on murine frontal cortex neuronal networks. , 2004, Toxicon : official journal of the International Society on Toxinology.

[131]  R. Munday Toxicology of Cyclic Imines: Gymnodimine, Spirolides, Pinnatoxins, Pteriatoxins, Prorocentrolide, Spiro-Prorocentrimine, and Symbioimines , 2008 .

[132]  M. Vieytes,et al.  A rapid microplate fluorescence method to detect yessotoxins based on their capacity to activate phosphodiesterases. , 2004, Analytical biochemistry.

[133]  Natalia Vilariño,et al.  Single laboratory validation of a surface plasmon resonance biosensor screening method for paralytic shellfish poisoning toxins. , 2010, Analytical chemistry.

[134]  F. Carrier,et al.  Inhibition of protein phosphatases‐1 and ‐2A with acanthifolicin , 1990, FEBS letters.

[135]  Carolyn T. Wong,et al.  Receptor binding assay for paralytic shellfish poisoning toxins: optimization and interlaboratory comparison. , 2003, Journal of AOAC International.

[136]  Bego√±a Espi√±a,et al.  Pharmacology of Pectenotoxins , 2008 .

[137]  W. Stühmer,et al.  A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II , 1989, FEBS letters.

[138]  L. Rhodes,et al.  Yessotoxin production by Gonyaulax spinifera , 2006 .

[139]  Miloslav Pravda,et al.  Novel electrochemical immunosensors for seafood toxin analysis. , 2002, Toxicon : official journal of the International Society on Toxinology.

[140]  D. Park Detection of ciguaterra and diarrheic shellfish toxins in finfish and shellfish with ciguatect kit , 1995 .

[141]  M. Quilliam Analysis of diarrhetic shellfish poisoning toxins in shellfish tissue by liquid chromatography with fluorometric and mass spectrometric detection. , 1995, Journal of AOAC International.

[142]  F. Chu,et al.  Indirect enzyme-linked immunosorbent assay for saxitoxin in shellfish. , 1985, Journal - Association of Official Analytical Chemists.

[143]  Christopher T Elliott,et al.  Development of a novel immunobiosensor method for the rapid detection of okadaic acid contamination in shellfish extracts , 2007, Analytical and bioanalytical chemistry.

[144]  A. Nozawa,et al.  Implication of brevetoxin B1 and PbTx-3 in neurotoxic shellfish poisoning in New Zealand by isolation and quantitative determination with liquid chromatography-tandem mass spectrometry. , 2003, Toxicon : official journal of the International Society on Toxinology.

[145]  K. Nicolaou,et al.  Azaspiracids modulate intracellular pH levels in human lymphocytes. , 2006, Biochemical and biophysical research communications.

[146]  T. Yasumoto,et al.  Toxicologic evaluation of yessotoxin. , 1997, Natural toxins.

[147]  C. Miles,et al.  Use of ELISA to identify Protoceratium reticulatum as a source of yessotoxin in Norway. , 2004, Toxicon : official journal of the International Society on Toxinology.

[148]  W. Catterall,et al.  Interaction of brevetoxin A with a new receptor site on the sodium channel. , 1985, Toxicon : official journal of the International Society on Toxinology.

[149]  K. Kawatsu,et al.  Rapid and highly sensitive enzyme immunoassay for quantitative determination of tetrodotoxin. , 1997, Japanese journal of medical science & biology.

[150]  P. Grothaus,et al.  Monoclonal antibody-based enzyme-linked immunoassays for the measurement of palytoxin in biological samples. , 1992, Toxicon : official journal of the International Society on Toxinology.

[151]  Daniel G. Baden,et al.  Brevetoxicosis: Red tides and marine mammal mortalities , 2005, Nature.

[152]  Joseph J Pancrazio,et al.  A portable microelectrode array recording system incorporating cultured neuronal networks for neurotoxin detection. , 2003, Biosensors & bioelectronics.

[153]  Ashok Mulchandani,et al.  Nano aptasensor for protective antigen toxin of anthrax. , 2010, Analytical chemistry.

[154]  Jiří Homola,et al.  Detection of low-molecular-weight domoic acid using surface plasmon resonance sensor , 2005 .

[155]  T. Carpenter,et al.  CLINICOPATHOLOGIC FEATURES OF SUSPECTED BREVETOXICOSIS IN DOUBLE-CRESTED CORMORANTS (PHALACROCORAX AURITUS) ALONG THE FLORIDA GULF COAST , 2002, Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians.

[156]  J. F. Lawrence,et al.  Three Rs Approaches in Marine Biotoxin Testing , 2006, Alternatives to laboratory animals : ATLA.

[157]  C. Vale,et al.  Marine toxins and the cytoskeleton: okadaic acid and dinophysistoxins , 2008, The FEBS journal.

[158]  M. Vieytes,et al.  Study of the neuronal effects of ouabain and palytoxin and their binding to Na,K-ATPases using an optical biosensor. , 2007, Toxicon : official journal of the International Society on Toxinology.

[159]  D. Gadsby,et al.  Ion permeation through the Na+,K+-ATPase , 2006, Nature.

[160]  Q. Cheng,et al.  New trends in instrumental design for surface plasmon resonance-based biosensors. , 2011, Biosensors & bioelectronics.

[161]  D. Shea Analysis of brevetoxins by micellar electrokinetic capillary chromatography and laser‐induced fluorescence detection , 1997, Electrophoresis.

[162]  M. Satake,et al.  Structures of Azaspiracid Analogs, Azaspiracid-4 and Azaspiracid-5, Causative Toxins of Azaspiracid Poisoning in Europe , 2001, Bioscience, biotechnology, and biochemistry.

[163]  Y. Shimada,et al.  Effects of pectenotoxin-1 on liver cells in vitro. , 1994, Natural toxins.

[164]  K. Wakamatsu,et al.  Diarrhetic Shellfish Toxin, Dinophysistoxin‐1, Is a Potent Tumor Promoter on Mouse Skin , 1988, Japanese journal of cancer research : Gann.

[165]  H. S. Wolff,et al.  iRun: Horizontal and Vertical Shape of a Region-Based Graph Compression , 2022, Sensors.

[166]  Natalia Vilariño,et al.  Functional assays for marine toxins as an alternative, high-throughput-screening solution to animal tests , 2009 .

[167]  D. Gadsby,et al.  Na+/K+-pump ligands modulate gating of palytoxin-induced ion channels , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[168]  A. Cembella,et al.  Characterization of spirolides a, c, and 13-desmethyl c, new marine toxins isolated from toxic plankton and contaminated shellfish. , 2001, Journal of natural products.

[169]  S. G. Bradley,et al.  A fatal poisoning from the Oregon rough-skinned newt (Taricha granulosa). , 1981, JAMA.

[170]  K. James,et al.  Detection of five new hydroxyl analogues of azaspiracids in shellfish using multiple tandem mass spectrometry. , 2003, Toxicon : official journal of the International Society on Toxinology.

[171]  G. Palleschi,et al.  Study of a toxin–alkaline phosphatase conjugate for the development of an immunosensor for tetrodotoxin determination , 2006, Analytical and bioanalytical chemistry.

[172]  S. Morton,et al.  Determination of okadaic acid content of dinoflagellate cells: a comparison of the HPLC-fluorescent method and two monoclonal antibody ELISA test kits. , 1996, Toxicon : official journal of the International Society on Toxinology.

[173]  T. Yasumoto,et al.  Clinical and laboratory findings implicating palytoxin as cause of ciguatera poisoning due to Decapterus macrosoma (mackerel). , 1989, Toxicon : official journal of the International Society on Toxinology.

[174]  W. Hardstaff,et al.  Rapid Extraction and Cleanup for Liquid Chromatographic Determination of Domoic Acid in Unsalted Seafood , 1995 .

[175]  L. Botana,et al.  A fluorimetric microplate assay for detection and quantitation of toxins causing paralytic shellfish poisoning. , 2003, Chemical research in toxicology.

[176]  P. Katikou,et al.  First episode of shellfish contamination by palytoxin-like compounds from Ostreopsis species (Aegean Sea, Greece). , 2008, Toxicon : official journal of the International Society on Toxinology.

[177]  N. Fusetani,et al.  Occurrence of a water soluble toxin in a parrotfish (Ypsiscarus ovifrons) which is probably responsible for parrotfish liver poisoning. , 1985, Toxicon : official journal of the International Society on Toxinology.

[178]  B. Espiña,et al.  Human muscarinic acetylcholine receptors are a target of the marine toxin 13-desmethyl C spirolide. , 2010, Chemical research in toxicology.

[179]  P. Beart,et al.  Neurotoxin domoic acid produces cytotoxicity via kainate- and ampa-sensitive receptors in cultured cortical neurones , 1997, Neurochemistry International.

[180]  Christopher T Elliott,et al.  Development of a monoclonal antibody binding okadaic acid and dinophysistoxins-1, -2 in proportion to their toxicity equivalence factors. , 2009, Toxicon : official journal of the International Society on Toxinology.

[181]  M. Vieytes,et al.  A fluorescent microplate assay for diarrheic shellfish toxins. , 1997, Analytical biochemistry.

[182]  Joseph J Pancrazio,et al.  Sensitivity of the Neuronal Network Biosensor to Environmental Threats , 2004, Journal of toxicology and environmental health. Part A.

[183]  Y. Hokama,et al.  Comparative analysis of purified Pacific and Caribbean ciguatoxin congeners and related marine toxins using a modified elisa technique , 2006, Journal of clinical laboratory analysis.

[184]  C. Vale,et al.  The problem of toxicity equivalent factors in developing alternative methods to animal bioassays for marine toxin detection , 2010 .

[185]  I Tothill,et al.  Surface plasmon resonance sensor for domoic acid based on grafted imprinted polymer. , 2004, Biosensors & bioelectronics.

[186]  R. Cole,et al.  On-line high-performance liquid chromatography-electrospray ionization mass spectrometry for the determination of brevetoxins in "red tide" algae. , 1995, Analytical chemistry.

[187]  P. Holland Analysis of Marine Toxins‚ÄîTechniques, Method Validation, Calibration Standards, and Screening Methods , 2008 .

[188]  R. Lewis Ion channel toxins and therapeutics: from cone snail venoms to ciguatera. , 2000, Therapeutic drug monitoring.

[189]  C. C. Yang,et al.  Tetrodotoxin poisoning in Taiwan: an analysis of poison center data. , 1996, Veterinary and human toxicology.

[190]  C. Vale,et al.  Cytotoxic effect of azaspiracid‐2 and azaspiracid‐2‐methyl ester in cultured neurons: Involvement of the c‐Jun N‐terminal kinase , 2008, Journal of neuroscience research.

[191]  M. Lazdunski,et al.  Ciguatoxin and brevetoxins share a common receptor site on the neuronal voltage‐dependent Na+ channel , 1987, FEBS letters.

[192]  C. Malaguti,et al.  Functional assay to measure yessotoxins in contaminated mussel samples. , 2003, Analytical biochemistry.

[193]  B. Espiña,et al.  Specific and dynamic detection of palytoxins by in vitro microplate assay with human neuroblastoma cells. , 2009, Bioscience reports.

[194]  Gustaaf M. Hallegraeff,et al.  Harmful algal blooms: a global overview , 1995 .

[195]  B. Espiña,et al.  Cytoskeletal toxicity of pectenotoxins in hepatic cells , 2008, British journal of pharmacology.

[196]  R. Combes The Mouse Bioassay for Diarrhetic Shellfish Poisoning: A Gross Misuse of Laboratory Animals and of Scientific Methodology , 2003, Alternatives to laboratory animals : ATLA.

[197]  Porter Hoagland,et al.  The Economic Effects of Harmful Algal Blooms , 2006 .

[198]  D. E. Evans,et al.  Surface hydrophobicity and dispersal of Pseudomonas aeruginosa from biofilms. , 1990, FEMS microbiology letters.

[199]  J. Otero Epidemiological Impact of Diarrheic Toxins , 2008 .

[200]  Van Dolah Fm Marine algal toxins: origins, health effects, and their increased occurrence. , 2000 .

[201]  Jean-Louis Marty,et al.  Enzymatic recycling-based amperometric immunosensor for the ultrasensitive detection of okadaic acid in shellfish. , 2008, Biosensors & bioelectronics.

[202]  N. Kulagina,et al.  Detection of marine toxins, brevetoxin-3 and saxitoxin, in seawater using neuronal networks. , 2006, Environmental science & technology.

[203]  Y. Hokama,et al.  A rapid enzyme-immunoassay for the detection of ciguatoxin in contaminated fish tissues. , 1983, Toxicon : official journal of the International Society on Toxinology.

[204]  R. Ratzlaff,et al.  Saxitoxin binding to synaptosomes, membranes, and solubilized binding sites from rat brain , 1979, The Journal of Membrane Biology.

[205]  A. These,et al.  Sensitive method for the determination of lipophilic marine biotoxins in extracts of mussels and processed shellfish by high-performance liquid chromatography-tandem mass spectrometry based on enrichment by solid-phase extraction. , 2009, Journal of chromatography. A.

[206]  G. Palleschi,et al.  Disposable immunosensor for the determination of domoic acid in shellfish. , 2004, Biosensors & bioelectronics.

[207]  A. Goksøyr,et al.  Determination of domoic acid toxins in shellfish by biosense ASP ELISA--a direct competitive enzyme-linked immunosorbent assay: collaborative study. , 2007, Journal of AOAC International.

[208]  P. Hess,et al.  Azaspiracid-1 alters the E-cadherin pool in epithelial cells. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[209]  A. H. Banner,et al.  A radioimmunoassay for the detection of ciguatoxin. , 1977, Toxicon : official journal of the International Society on Toxinology.

[210]  R. W. Janes alpha-Conotoxins as selective probes for nicotinic acetylcholine receptor subclasses. , 2005, Current opinion in pharmacology.

[211]  L. Botana The Mouse Bioassay as a Universal Detector , 2008 .

[212]  C. Miles,et al.  Acute toxicity of gymnodimine to mice. , 2004, Toxicon : official journal of the International Society on Toxinology.

[213]  D. Hilgemann From a pump to a pore: How palytoxin opens the gates , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[214]  S. Døskeland,et al.  Sensitive detection of apoptogenic toxins in suspension cultures of rat and salmon hepatocytes. , 1998, Toxicon : official journal of the International Society on Toxinology.

[215]  J. Silke,et al.  Azaspiracid, a New Marine Toxin Having Unique Spiro Ring Assemblies, Isolated from Irish Mussels, Mytilus edulis. , 1999 .

[216]  P. de la Iglesia,et al.  Determination of yessotoxins and pectenotoxins in shellfish by capillary electrophoresis-electrospray ionization-mass spectrometry , 2009, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[217]  D. Baden,et al.  Brevetoxicosis in Manatees (Trichechus manatus latirostris) from the 1996 Epizootic: Gross, Histologic, and Immunohistochemical Features , 1998, Toxicologic pathology.

[218]  F. Braet,et al.  New anti‐actin drugs in the study of the organization and function of the actin cytoskeleton , 1999, Microscopy research and technique.

[219]  D. Baden,et al.  Modified immunoassays for polyether toxins: implications of biological matrixes, metabolic states, and epitope recognition. , 1995, Journal of AOAC International.

[220]  Natalia Vilariño,et al.  Paralytic shellfish poisoning detection by surface plasmon resonance-based biosensors in shellfish matrixes. , 2007, Analytical chemistry.

[221]  V. Procacci,et al.  Respiratory illness as a reaction to tropical algal blooms occurring in a temperate climate. , 2005, JAMA.

[222]  H. Endo,et al.  Development of an ultra high sensitive tissue biosensor for determination of swellfish poisoning, tetrodotoxin. , 1996, Biosensors & bioelectronics.

[223]  B. Espiña,et al.  Marine toxins and the cytoskeleton: pectenotoxins, unusual macrolides that disrupt actin , 2008, The FEBS journal.

[224]  Z. Amzil,et al.  Domoic acid accumulation in French shellfish in relation to toxic species of Pseudo-nitzschia multiseries and P. pseudodelicatissima. , 2001, Toxicon : official journal of the International Society on Toxinology.

[225]  R. E. Gawley,et al.  Selective detection of saxitoxin over tetrodotoxin using acridinylmethyl crown ether chemosensor. , 2005, Toxicon : official journal of the International Society on Toxinology.

[226]  H. Fujiki,et al.  Production of antibodies to palytoxin: neutralization of several biological properties of palytoxin. , 1987, Toxicon : official journal of the International Society on Toxinology.

[227]  L. Wiklund,et al.  Magnesium intake, drinking water, and risk of colorectal cancer. , 2005, JAMA.

[228]  C. Holmes,et al.  Molecular mechanisms underlying inhibition of protein phosphatases by marine toxins. , 1999, Frontiers in bioscience : a journal and virtual library.

[229]  K. James,et al.  Brevetoxins: Structure, Toxicology, and Origin , 2007 .

[230]  Jean-Louis Marty,et al.  Enzyme sensor for the electrochemical detection of the marine toxin okadaic acid. , 2007, Analytica chimica acta.

[231]  P. Hess,et al.  Development of an ultra-performance liquid chromatography-mass spectrometry method for the detection of lipophilic marine toxins. , 2007, Journal of chromatography. A.

[232]  Zoran Radić,et al.  Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism , 2010, Proceedings of the National Academy of Sciences.

[233]  R. Lewis,et al.  Characterization of ciguatoxins and ciguatoxin congeners present in ciguateric fish by gradient reverse-phase high-performance liquid chromatography/mass spectrometry. , 1997, Toxicon : official journal of the International Society on Toxinology.

[234]  W. Catterall Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. , 1980, Annual review of pharmacology and toxicology.

[235]  Pratik Banerjee,et al.  Mammalian cell-based biosensors for pathogens and toxins. , 2009, Trends in biotechnology.

[236]  Josef Schlatter,et al.  Opinion of the Scientific Panel on Contaminants in the food chain on a request from the European Commission on marine biotoxines in shellfish okadaic acid and analogues , 2008 .

[237]  P. Katikou Palytoxin and Analogues: Ecobiology and Origin, Chemistry, Metabolism, and Chemical Analysis , 2008 .

[238]  J. Cooney,et al.  Isolation of pectenotoxin-2 from Dinophysis acuta and its conversion to pectenotoxin-2 seco acid, and preliminary assessment of their acute toxicities. , 2004, Toxicon : official journal of the International Society on Toxinology.

[239]  J. Ramsdell,et al.  Development and preliminary validation of a microtiter plate-based receptor binding assay for paralytic shellfish poisoning toxins. , 1997, Toxicon : official journal of the International Society on Toxinology.

[240]  B. Jeffery,et al.  Amnesic shellfish poison. , 2004, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[241]  P. Thibault,et al.  Analysis of paralytic shellfish poisons by capillary electrophoresis. , 1991, Journal of chromatography.

[242]  P. Vale,et al.  Detection of Diarrheic Shellfish Poisoning and Azaspiracid Toxins in Moroccan Mussels: Comparison of the LC-MS Method with the Commercial Immunoassay Kit , 2008, Marine drugs.

[243]  A. Tubaro,et al.  Methodological improvement of the protein phosphatase inhibition assay for the detection of okadaic acid in mussels. , 1999, Natural toxins.

[244]  M. Vieytes,et al.  Kinetic analysis of the interaction between yessotoxin and analogues and immobilized phosphodiesterases using a resonant mirror optical biosensor. , 2005, Chemical research in toxicology.

[245]  W. Catterall,et al.  The sodium channel from rat brain. Purification and subunit composition. , 1984, The Journal of biological chemistry.

[246]  C. Vale,et al.  First toxicity report of tetrodotoxin and 5,6,11-trideoxyTTX in the trumpet shell Charonia lampas lampas in Europe. , 2008, Analytical chemistry.

[247]  J. Cooney,et al.  Polyhydroxylated amide analogs of yessotoxin from Protoceratium reticulatum. , 2005, Toxicon : official journal of the International Society on Toxinology.

[248]  B. Espiña,et al.  Lactone Ring of Pectenotoxins: a Key Factor for their Activity on Cytoskeletal Dynamics , 2007, Cellular Physiology and Biochemistry.

[249]  B. Codispoti,et al.  Characterization of natural toxins with inhibitory activity against serine/threonine protein phosphatases. , 1994, Toxicon : official journal of the International Society on Toxinology.

[250]  N. Vilariño Marine toxins and the cytoskeleton: azaspiracids , 2008, The FEBS journal.

[251]  M. Vieytes,et al.  Resonant mirror biosensor detection method based on yessotoxin-phosphodiesterase interactions. , 2004, Analytical biochemistry.

[252]  C. Miles,et al.  Enzyme-linked immunosorbent assay for the detection of yessotoxin and its analogues. , 2004, Journal of agricultural and food chemistry.

[253]  G. Guilbault,et al.  Development of an ultrasensitive immunoassay for rapid measurement of okadaic acid and its isomers. , 1999, Analytical chemistry.

[254]  Lange Wr Puffer fish poisoning. , 1990 .

[255]  E. Habermann Palytoxin acts through Na+,K+-ATPase. , 1989, Toxicon : official journal of the International Society on Toxinology.

[256]  M. Quilliam Committee on Natural Toxins: Phycotoxins , 1999 .

[257]  M. Vieytes,et al.  Quantification of yessotoxin using the fluorescence polarization technique and study of the adequate extraction procedure. , 2005, Analytical biochemistry.

[258]  C. Miles,et al.  Integrated enzyme-linked immunosorbent assay screening system for amnesic, neurotoxic, diarrhetic, and paralytic shellfish poisoning toxins found in New Zealand. , 2001, Journal of AOAC International.