Marine Biotoxins

  • Aníbal Martínez
  • Alejandro Garrido-Maestu
  • Begoña Ben-Gigirey
  • María José Chapela
  • Virginia González
  • Juan M. Vieites
  • Ana G. Cabado
Chapter

Abstract

This chapter revises current knowledge on marine biotoxins that are known nowadays, considering all the distinct groups based on chemical structure and lipophilic or hydrophilic characteristics. Diarrheic shellfish poisoning (DSP ), paralytic shellfish poisoning (PSP), amnesic shellfish poisoning (ASP ), azaspiracid shellfish poisoning (AZP ), ciguatera fish poisoning (CFP ) are some of the groups that will be reviewed in this chapter.

The recent development and application of advanced technologies from the generically defined -omics sciences coupled with bioinformatics platforms has been included in this chapter in order to understand the ecology and evolution of phytoplankton species and bloom dynamics. Dinoflagellate toxins are structurally and functionally diverse, and many present unique biological activities.

The literature and information regarding the biological activities and the potential application of these phycotoxins has been gathered in this book section.

Keywords

Molecularly Imprint Polymer Domoic Acid Paralytic Shellfish Poisoning Shellfish Poisoning Receptor Binding Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
AFLP

amplified fragment length polymorphism

AMPA

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ASP

amnesic shellfish poisoning

ATP

adenosine triphosphate

AZA

azaspiracid

AZP

azaspiracid shellfish poisoning

BTX

brevetoxin

C-CTX

Caribbean-CTX

CFP

ciguatera fish poisoning

CGC

cerebellar granule cell

CGN

cerebellar granule neuron

CI

cyclic imine

cyclic imines

CSP

cell surface protein

CTX

ciguatoxin

DA

domoic acid

DGGE

denaturing gradient gel electrophoresis

DNA

deoxyribonucleic acid

DSP

diarrhetic shellfish poisoning

DTX

dinophysis toxin

ELISA

enzyme-linked immunosorbent assay

EST

express sequence tag

EU

European Union

FDA

Food and Drug Administration

FETAX

frog embryo teratogenesis assay-xenopus

FISH

fluorescence in situ hybridization

GC-TOF-MS

chromatography-time-of-flight mass spectrometry

GCL

glutamate cysteine ligase

GLDC

glutamate decarboxylase

GSH

glutathione

GYM

gymnodimine

HAB

harmful algal bloom

HPLC

high-performance liquid chromatography

HRP

horseradish peroxidase

HeLa

human cervix carcinoma cells

HepG2

hepatoma cell line

I-CTX

Indian-CTX

IAC

internal amplification control

IAEA

International Atomic Energy Agency

ITS

internal transcribed spacer

LC-MS

liquid chromatography-mass spectrometry

LC

liquid chromatography

LDLR

low-density lipoprotein receptor

LT

lipophilic toxin

MAP

mitogen-activated protein

MBA

mouse bioassay

MCF

Michigan Cancer Foundation-7

MIP

molecularly imprinted polymer

MS

mass spectroscopy

MTX

maitotoxin

Mbp

million base pairs

NMDA

N-metyl-d-aspartic acid

NOAA

National Oceanic and Atmospheric Administration

NO

nitric oxide

NSP

neurotoxic shellfish poisoning

OA

okadaic acid

OTAB

octyl-trimethyl ammonium bromide

P-CTX

Pacific-CTX

PCR

polymerase chain reaction

PET

photoinduced electron transfer

PPC

proparacaine

PSP

paralytic shellfish poisoning

PST

paralytic shellfish poisoning toxin

PTX2SA

PTX2 seco acid

PTX

pectenotoxin

PbTx

brevetoxin

PlTX

palytoxin

PnTX

pinnatoxin

PtTX

pteriatoxin

RAPD

random amplified polymorphic DNA

RBA

Receptor Binding Assay

RFLP

restriction fragment length polymorphism

RIA

radioimmunoassay

RNA

ribonucleic acid

SNP

single nucleotide polymorphisms

SPR

surface plasmon resonance

SPX

spirolide

SSCP

single stranded conformation polymorphism

SSR

short sequence repeats

STX

saxitoxin

TNF

tumor necrosis factor

TTX

11-[ 3 Open image in new windowH]-tetrodotoxin

UV

ultraviolet

VGIC

voltage-gated ion channels

VGSC

voltage-gated Na + Open image in new window channel

YTX

yessotoxin

cAMP

cyclic adenosine monophosphate

cDNA

complementary DNA

epi-DA

epi-domoic acid

i.p.

intraperitoneal

iso-DA A–H

isodomoic acids A, B, C, D, E, F, G, and H

mRNA

messenger RNA

qPCR

quantitative PCR

rDNA

ribosomal DNA

rRNA

ribosomal RNA

This is a preview of subscription content, log in to check access.

References

  1. [37.1]
    European Parliament: Regulation (EC) No 853/2004 of the European Parliament and of the council of 29 April 2004 laying down specific hygiene rules for on the hygiene of foodstuffs, Off. J. Eur. Union L 139, 55–205 (2004)Google Scholar
  2. [37.2]
    M. Andjelkovic: Emerging marine biotoxins – Report from the seminar, Semin. Emerg. Toxins, Vigo-Pontevedra (European Union Reference Labratory for Marine Biotoxins, Vigo Pontevedra Spain 2012)Google Scholar
  3. [37.3]
    M. Kat: Dinophysis acuminata blooms in the Dutch coastal area related to diarrhetic mussel poisoning in the Dutch Waddensea, Sarsia 68(1), 81–84 (1983)Google Scholar
  4. [37.4]
    M. Kat: Diarrhetic mussel poisoning in the Netherlands related to the dinoflagellate dinophysis acuminata, Antonie Van Leeuwenhoek J. Microbiol. 49(4-5), 417–427 (1983)Google Scholar
  5. [37.5]
    T. Yasumoto, Y. Oshima, M. Yamaguchi: Occurrence of a new type of shellfish poisoning in the Tohoku district, Bull. Jpn. Soc. Sci. Fish. 44, 1249–1255 (1978)CrossRefGoogle Scholar
  6. [37.6]
    A. Otero, M.J. Chapela, M. Atanassova, J.M. Vieites, A.G. Cabado: Biological activities and potential applications of marine biotoxins. In: Marine Biomaterials, ed. by S.-K. Kim (CRC/Taylor Francis, Boca Raton 2013)Google Scholar
  7. [37.7]
    European Food Safety Authority: Marine biotoxins in shellfish – Domoic acid. Scientific Opinion of the Panel on Contaminants in the Food chain, EFSA Journal 1181, 1–62 (2009)Google Scholar
  8. [37.8]
    P. Vale, M.A. Sampayo: Esterification of DSP toxins by Portuguese bivalves from the Northwest coast determined by LC-MS – A widespread phenomenon, Toxicon 40(1), 33–42 (2002)CrossRefGoogle Scholar
  9. [37.9]
    P. Cohen: The structure and regulation of protein phosphatases, Annu. Rev. Biochem. 58, 453–508 (1989)CrossRefGoogle Scholar
  10. [37.10]
    T.A. Haystead, A.T.R. Sim, D. Carling, R.C. Honnor, Y. Tsukitani, P. Cohen, D.G. Hardie: Effects of the tumor promoter okadaic acid on intracellular protein phosphorylation and metabolism, Nature 337, 78–81 (1989)CrossRefGoogle Scholar
  11. [37.11]
    T. Yasumoto, M. Murata, Y. Oshima, M. Sano, G.K. Matsumoto, J. Clardy: Diarrhetic shellfish toxins, Tetrahedron 41(6), 1019–1025 (1985)CrossRefGoogle Scholar
  12. [37.12]
    J. Blanco, G. Alvarez, E. Uribe: Identification of pectenotoxins in plankton, filter feeders, and isolated cells of a Dinophysis acuminata with an atypical toxin profile, from Chile, Toxicon 49(5), 710–716 (2007)CrossRefGoogle Scholar
  13. [37.13]
    B. Paz, A.H. Daranas, M. Norte, P. Riobo, J.M. Franco, J.J. Fernandez: Yessotoxins, a group of marine polyether toxins: An overview, Mar. Drugs 6(2), 73–102 (2008)CrossRefGoogle Scholar
  14. [37.14]
    M. Murata, M. Kumagai, J.S. Lee, T. Yasumoto: Isolation and structure of yessotoxin, a novel polyether compound implicated in diarrhetic shellfish poisoning, Tetrahedron Lett. 28, 5869–5872 (1987)CrossRefGoogle Scholar
  15. [37.15]
    K.J. Lee, J.S. Mok, K.C. Song, H. Yu, J.H. Jung, J.H. Kim: Geographical and annual variation in lipophilic shellfish toxins from oysters and mussels along the South coast of Korea, J. Food Prot. 74(12), 2127–2133 (2011)CrossRefGoogle Scholar
  16. [37.16]
    G. Alvarez, E. Uribe, R. Diaz, M. Braun, C. Marino, J. Blanco: Bloom of the Yessotoxin producing dinoflagellate Protoceratium reticulatum (Dinophyceae) in Northern Chile, J. Sea Res. 65(4), 427–434 (2011)CrossRefGoogle Scholar
  17. [37.17]
    T. Yasumoto, A. Takizawa: Fluorometric measurement of yessotoxins in shellfish by high-pressure liquid chromatography, Biosci. Biotechnol. Biochem. 61(10), 1775–1777 (1997)CrossRefGoogle Scholar
  18. [37.18]
    C.O. Miles, A.L. Wilkins, A.D. Hawkes, A.I. Selwood, D.J. Jensen, R. Munday, J.M. Cooney, V. Beuzenberg: Polyhydroxylated amide analogs of yessotoxin from Protoceratium reticulatum, Toxicon 45(1), 61–71 (2005)CrossRefGoogle Scholar
  19. [37.19]
    H. Ogino, M. Kumagai, T. Yasumoto: Toxicological evaluation of yessotoxin, Nat. Toxins 5, 255–259 (1997)CrossRefGoogle Scholar
  20. [37.20]
    L.A. De la Rosa, A. Alfonso, N. Vilariño, M.R. Vieytes, L.M. Botana: Modulation of cytosolic calcium levels of human lymphocytes by yessotoxin, a novel marine phycotoxin, Biochem. Pharmacol. 61(7), 827–833 (2001)CrossRefGoogle Scholar
  21. [37.21]
    M.J. Twiner, R. El-Ladki, J. Kilcoyne, G.J. Doucette: Comparative effects of marine algal toxins azaspiracid-1,-2, and-3 on T. Jurkat lymphocyte cells, Chem. Res. Toxicol. 25, 747–754 (2012)CrossRefGoogle Scholar
  22. [37.22]
    G. Alvarez, E. Uribe, P. Avalos, C. Marino, J. Blanco: First identification of azaspiracid and spirolides in Mesodesma donacium and Mulinia edulis from Northern Chile, Toxicon 55(2/3), 638–641 (2010)CrossRefGoogle Scholar
  23. [37.23]
    A. López-Rivera, K. O'Callaghan, M. Moriarty, D. O'Driscoll, B. Hamilton, M. Lehane, K.J. James, A. Furey: First evidence of azaspiracids (AZAs): A family of lipophilic polyether marine toxins in scallops (Argopecten purpuratus) and mussels (Mytilus chilensis) collected in two regions of Chile, Toxicon 55(4), 692–701 (2009)CrossRefGoogle Scholar
  24. [37.24]
    H. Taleb, P. Vale, R. Amanhir, A. Benhadouch, R. Sagou, A. Chafik: First detection of azaspiracids in mussels in North West Africa, J. Shelfish Res. 25, 1067–1070 (2006)CrossRefGoogle Scholar
  25. [37.25]
    M.J. Twiner, N. Rehmann, P. Hess, G.J. Doucette: Azaspiracid shellfish poisoning: A review on the chemistry, ecology, and toxicology with an emphasis on human health impacts, Mar. Drugs 6(2), 39–72 (2008)CrossRefGoogle Scholar
  26. [37.26]
    R. Ueoka, A. Ito, M. Izumikawa, S. Maeda, M. Takagi, K. Shin-ya, M. Yoshida, R.W.M. van Soest, S. Matsunaga: Isolation of Azaspiracid-2 from a marine sponge Echinoclathria sp., as a potent cytotoxin, Toxicon 53(6), 680–684 (2009)Google Scholar
  27. [37.27]
    K.J. James, C. Moroney, C. Roden, M. Satake, T. Yasumoto, M. Lehane, A. Furey: Ubiquitous 'benign' alga emerges as the cause of shellfish contamination responsible for the human toxic syndrome, azaspiracid poisoning, Toxicon 41, 145–151 (2003)CrossRefGoogle Scholar
  28. [37.28]
    K. Toebe, A.R. Joshi, P. Messtorff, U. Tillmann, A. Cembella, U. John: Molecular discrimination of taxa within the dinoflagellate genus Azadinium, the source of azaspiracid toxins, J. Plankton Res. 35(1), 225–230 (2013)CrossRefGoogle Scholar
  29. [37.29]
    European Food Safety Authority: Opinion of the scientific panel on contaminants in the food chain on a request from the European commission on marine biotoxins in shellfish – Azaspiracids, Eur. Food Saf. Auth. J. 723, 1–52 (2008)Google Scholar
  30. [37.30]
    European Food Safety Authority: Marine biotoxins in shellfish – Saxitoxin group, Eur. Food Saf. Auth. J. 1019, 1–46 (2009)Google Scholar
  31. [37.31]
    L. McCauley, D.L. Erdner, S. Nagai, M. Richlen, D.M. Anderson: Biogeographic analysis of the globally distributed harmful algal bloom species Alexandrium minutum (Dinophyceae) based on rRNA gene sequences and microsatellite markers, J. Phycol. 45, 454–463 (2009)CrossRefGoogle Scholar
  32. [37.32]
    WHOI (Ed.): Harmful algae (2007), http://www.whoi.edu/redtide/page.do?pid=18103 (accessed January 31, 2012)
  33. [37.33]
    S.M. Etheridge: Paralytic shellfish poisoning: Seafood safety and human health perspectives, Toxicon 56, 108–122 (2010)CrossRefGoogle Scholar
  34. [37.34]
    K.A. Lefebvre, A. Robertson: Domoic acid and human exposure risks: A review, Toxicon 56(2), 218–230 (2010)CrossRefGoogle Scholar
  35. [37.35]
    Y. He, A. Fekete, G. Chen, M. Harir, L. Zhang, P. Tong, P. Schmitt-Kopplin: Analytical approaches for an important shellfish poisoning agent: Domoic Acid, J. Agric. Food Chem. 58(22), 11525–11533 (2010)CrossRefGoogle Scholar
  36. [37.36]
    O.M. Pulido: Domoic acid toxicologic pathology: A review, Mar. Drugs 6(2), 180–219 (2008)CrossRefGoogle Scholar
  37. [37.37]
    J.S. Ramsdell: The molecular and integrative basis to domoic acid toxicity. In: Phycotoxins Chemistry and Biochemistry, ed. by L.M. Botana (Blackwell Publishing, Oxford 2007) pp. 223–250CrossRefGoogle Scholar
  38. [37.38]
    Y. Kotaki: Ecobiology of amnesic shellfish toxin producing diatoms. In: Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 383–396CrossRefGoogle Scholar
  39. [37.39]
    J.L.C. Wright, K. Boyd, A.S.W. de Freitas, M. Falk, R. Foxall, W.D. Jamieson, A.W. Laycock, A.W. McCulloch, A.G. McInnes, P. Odense, V.P. Pathak, M.A. Quilliam, M.A. Ragan, P.G. Sim, J.A. Thibault, J.A. Walter, M. Gilgan, D.J.A. Richard, D. Dewar: Identification of domoic acid, a neuroexcitatory amino acid, in toxic mussels from eastern Prince Edward Island, Can. J. Chem. 67, 481–490 (1989)CrossRefGoogle Scholar
  40. [37.40]
    M.A. Quilliam, P.G. Sim, A.W. McCulloch, A.G. McInnes: High-performance liquidchromatography of domoic acid, a marine neurotoxin, with application to shellfish and plankton, Int. J. Environ. Anal. Chem. 36(3), 139–154 (1989)CrossRefGoogle Scholar
  41. [37.41]
    Y. Djaoued, M. Thibodeau, J. Robichaud, S. Balaji, S. Priya, N. Tchoukanova, S.S. Bates: Photocatalytic degradation of domoic acid using nanocrystalline TiO${}_{2}$ thin films, J. Photochem. Photobiol. 193, 271–283 (2008)CrossRefGoogle Scholar
  42. [37.42]
    J.L.C. Wright, M. Falk, A.G. McInnes, J.A. Walter: Identification of isodomoic acid-d and two new geometrical-isomers of domoic acid in toxic mussels, Can. J. Chem. 68(1), 22–25 (1990)CrossRefGoogle Scholar
  43. [37.43]
    J.L.C. Wright, M.A. Quilliam: Methods for domoic acid, the amnesic shellfish poisoning (ASP) toxin. In: Manual on Harmful Marine Microalgae, ed. by G.M. Hallegraeff, D. Anderson, A.D. Cembella (UNESCO, Paris 1995) pp. 115–135Google Scholar
  44. [37.44]
    M. Quilliam: Chemical methods for lipophillic shellfish toxins. In: Manual on Harmful Marine Microalgae, ed. by G. Hallegraeff, D.M. Anderson, A.D. Cembella (UNESCO, Paris 2003) pp. 211–245Google Scholar
  45. [37.45]
    European Food Safety Authority: Scientific Opinion on marine biotoxins in shellfish – Emerging toxins: Ciguatoxin group, Eur. Food Saf. Auth. J. 8(6), 1627–1638 (2010)Google Scholar
  46. [37.46]
    A. Caillaud, P. de la Iglesia, H.T. Darius, S. Pauillac, K. Aligizaki, S. Fraga, M. Chinain, J. Diogene: Update on methodologies available for ciguatoxin determination: Perspectives to confront the onset of ciguatera fish poisoning in Europe, Mar. Drugs 8(6), 1838–1907 (2010)CrossRefGoogle Scholar
  47. [37.47]
    G.K. Isbister, M.C. Kiernan: Neurotoxic marine poisoning, Lancet Neurol. 4(4), 219–228 (2005)CrossRefGoogle Scholar
  48. [37.48]
    R.W. Litaker, M.W. Vandersea, M.A. Faust, S.R. Kibler, M. Chinain, M.J. Holmes, W.C. Holland, P.A. Tester: Taxonomy of Gambierdiscus including four new species, Gambierdiscus caribaeus, Gambierdiscus carolinianus, Gambierdiscus carpenteri and Gambierdiscus ruetzleri (Gonyaulacales, Dinophyceae), Phycologia 48(5), 344–390 (2009)CrossRefGoogle Scholar
  49. [37.49]
    R.W. Litaker, M.W. Vandersea, M.A. Faust, S.R. Kibler, A.W. Naua, W.C. Holland, M. Chinain, M.J. Holmes, P.A. Tester: Global distribution of ciguatera causing dinoflagellates in the genus Gambierdiscus, Toxicon 56, 711–730 (2010)CrossRefGoogle Scholar
  50. [37.50]
    K. Aligizaki, G. Nikolaidis: Morphological identification of two tropical dinoflagellates of the genera Gambierdiscus and Sinophysis in the Mediterranean Sea, J. Biol. Res.-Thessalon. 9, 75–82 (2008)Google Scholar
  51. [37.51]
    J.P. Vernoux, R.J. Lewis: Isolation and characterisation of Caribbean ciguatoxins from the horse-eye jack (Caranx latus), Toxicon 35, 889–900 (1997)CrossRefGoogle Scholar
  52. [37.52]
    I. Pottier, J. Vernoux, A. Jones, R. Lewis: Analysis of toxin profiles in three different fish species causing ciguatera fish poisoning in Guadeloupe, French West Indies, Food Addit. Contam. 19, 1034–1042 (2002)CrossRefGoogle Scholar
  53. [37.53]
    B. Hamilton, M. Hurbungs, J.P. Vernoux, A. Jones, R.J. Lewis: Isolation and characterization of Indian Ocean ciguatoxin, Toxicon 40, 685–693 (2002)CrossRefGoogle Scholar
  54. [37.54]
    C.C. Davis: Gymnodinium Brevis Sp. Nov. A cause of discolored water and animal mortality in the gulf of Mexico, Bot. Gaz. 109(3), 358–360 (2002)CrossRefGoogle Scholar
  55. [37.55]
    European Food Safety Authority: Panel on contaminants in the food chain (CONTAM), Scientific opinion on marine biotoxins in shellfish – emerging toxins: Brevetoxin group, Eur. Food Saf. Auth. J. 8(7), 1–29 (2010)Google Scholar
  56. [37.56]
    G. Gunter, F.G.W. Smith, R.H. Williams: Mass mortality of marine animals on the lower west coast of Florida, November 1946–January 1947, Science 105(2723), 256–257 (1947)CrossRefGoogle Scholar
  57. [37.57]
    FAO (Ed.): Marine biotoxins. In: Food and Nutrition Paper, Vol. 80, Available from http://www.fao.org/docrep/007/y5486e/y5486e00.HTM (2004)
  58. [37.58]
    L.E. Fleming, B. Kirkpatrick, L.C. Backer, C.J. Walsh, K. Nierenberg, J. Clark, A. Reich, J. Hollenbeck, J. Benson, Y.S. Cheng, J. Naar, R. Pierce, A.J. Bourdelais, W.M. Abraham, G. Kirkpatrick, J. Zaias, A. Wanner, E. Mendes, S. Shalat, P. Hoagland, W. Stephan, J.A. Bean, S. Watkins, T. Clarke, M. Byrne, D.G. Baden: Review of Florida red tide and human health effects, Harmful Algae 10, 224–233 (2011)CrossRefGoogle Scholar
  59. [37.59]
    F. Van Dolah: Marine algal toxins: Origins, health effects, and their increased occurrence, Environ. Health Perspect. 108(Suppl. 1), 133–141 (2000)CrossRefGoogle Scholar
  60. [37.60]
    D.G. Baden, A.J. Bourdelais, H. Jacocks, S. Michelliza, J. Naar: Natural and derivative brevetoxins: Historical background, multiplicity, and effects, Environ. Health Perspect. 113(5), 621–625 (2005)CrossRefGoogle Scholar
  61. [37.61]
    J.H. Landsberg: The effects of harmful algal blooms on aquatic organisms, Rev. Fish. Sci. 10(2), 113–390 (2002)CrossRefGoogle Scholar
  62. [37.62]
    S.M. Plakas, R.W. Dickey: Advances in monitoring and toxicity assessment of brevetoxins in molluscan shellfish, Toxicon 56(2), 137–149 (2010)CrossRefGoogle Scholar
  63. [37.63]
    J.S. Ramsdell: The molecular and integrative basis to brevetoxin toxicity. In: Seafood and Freshwater Toxins: Pharmacology, Physiology and Detection, ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 519–550CrossRefGoogle Scholar
  64. [37.64]
    B.L. Williams: Behavioral and chemical ecology of marine organisms with respect to tetrodotoxin, Mar. Drugs 8(3), 381–398 (2010)CrossRefGoogle Scholar
  65. [37.65]
    B.D. Gessner, B. McLaughlin: Epidemiologic impact of toxic episodes: Neurotoxic toxins. In: Seafood and Freshwater Toxins. Pharmacology, Physiology and Detection, ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 77–103Google Scholar
  66. [37.66]
    Y. Bentur, J. Ashkar, Y. Lurie, Y. Levy, Z. Azzam, M. Litmanovich: Lessepsian migration and tetrodotoxin poisoning due to Lagocephalus sceleratus in the eastern Mediterranean, Toxicon 52, 964–968 (2008)CrossRefGoogle Scholar
  67. [37.67]
    P. Rodriguez, A. Alfonso, C. Vale, C. Alfonso, P. Vale, A. Tellez, L.M. Botana: First toxicity report of tetrodotoxin and 5,6,11-trideoxyTTX in the trumpet shell Charonia lampas lampas in Europe, Anal. Chem. 80, 5622–5629 (2008)CrossRefGoogle Scholar
  68. [37.68]
    R. Chau, J.A. Kalaitzis, B.A. Neilan: On the origins and biosynthesis of tetrodotoxin, Aquat. Toxicol. 104(1/2), 61–72 (2011)CrossRefGoogle Scholar
  69. [37.69]
    C.H. Lee, P.C. Ruben: Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxin, Channels 2, 407–412 (2008)CrossRefGoogle Scholar
  70. [37.70]
    C.B. Berde, U. Athiraman, B. Yahalom, D. Zurakowski, G. Corfas, C. Bognet: Tetrodotoxin-bupivacaine-epinephrine combinations for prolonged local anesthesia, Mar. Drugs 9(12), 2717–2728 (2011)CrossRefGoogle Scholar
  71. [37.71]
    R.E. Moore, P.J. Scheuer: Palytoxin – New marine toxin from a coelenterate, Science 172(3982), 495 (1971)CrossRefGoogle Scholar
  72. [37.72]
    J.R. Deeds, M.D. Schwartz: Human risk associated with palytoxin exposure, Toxicon 56(2), 150–162 (2010)CrossRefGoogle Scholar
  73. [37.73]
    European Food Safety Authority: Panel on contaminants in the food chain (CONTAM); Scientific opinion on marine biotoxins in shellfish – Palytoxin group, Eur. Food Saf. Auth. J. 7(12), 1393–1340 (2009)Google Scholar
  74. [37.74]
    P. Ciminiello, C. Dell'Aversano, E. Dello Iacovo, E. Fattorusso, M. Forino, L. Grauso, L. Tartaglione, C. Florio, P. Lorenzon, M. De Bortoli, A. Tubaro, M. Poli, G. Bignami: Stereostructure and biological activity of 42-hydroxy-palytoxin: A new palytoxin analogue from hawaiian Palythoa subspecies, Chem. Res. Toxicol. 22(11), 1851–1859 (2009)CrossRefGoogle Scholar
  75. [37.75]
    P. Riobo, J.M. Franco: Palytoxins: Biological and chemical determination, Toxicon 57(3), 368–375 (2011)CrossRefGoogle Scholar
  76. [37.76]
    D.W. Hilgemann: From a pump to a pore: How palytoxin opens the gates, Proc. Natl. Acad. Sci. USA 100(2), 386–388 (2003)CrossRefGoogle Scholar
  77. [37.77]
    M.C. Louzao, I.R. Ares, E. Cagide, B. Espina, N. Vilarino, A. Alfonso, M.R. Vieytes, L.M. Botana: Palytoxins and cytoskeleton: An overview, Toxicon 57(3), 460–469 (2011)CrossRefGoogle Scholar
  78. [37.78]
    A.M. Rodrigues, A.C.G. Almeida, A.F.C. Infantosi: Infantosi: Effect of palytoxin on the sodium-potassium pump: Model and simulation, Phys. Biol. 5(3), 036005 (2008)CrossRefGoogle Scholar
  79. [37.79]
    V. Ramos, V. Vasconcelos: Palytoxin and analogs: Biological and ecological effects, Mar. Drugs 8(7), 2021–2037 (2010)CrossRefGoogle Scholar
  80. [37.80]
    B. Krock, U. Tillmann, U. John, A.D. Cembella: Characterization of azaspiracids in plankton size-fractions and isolation of an azaspiracid-producing dinoflagellate from the North Sea, Harmful Algae 8(2), 254–263 (2009)CrossRefGoogle Scholar
  81. [37.81]
    A. Otero, M.J. Chapela, M. Atanassova, J.M. Vieites, A.G. Cabado: Ciclyc imines chemistry and mechanism of action: A review, Chem. Res. Toxicol. 24(11), 1817–1829 (2011)CrossRefGoogle Scholar
  82. [37.82]
    A. Cembella, B. Krock: Cyclic imine toxins: Chemistry, biogeography, biosynthesis and pharmacology. In: Seafood and Freshwaters Toxins: Pharmacology, Physiology and Detection, ed. by L.A. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 561–580Google Scholar
  83. [37.83]
    T.M. Hu, J.M. Curtis, Y. Oshima, M.A. Quilliam, J.A. Walter, W.M. Watsonwright, J.L.C. Wright: Spirolide-B and Spirolide-D, two novel macrocycles isolated from the digestive glands of shellfish, J. Chem. Soc.-Chem. Commun. 20, 2159–2161 (1995)CrossRefGoogle Scholar
  84. [37.84]
    T. Seki, M. Satake, L. Mackenzie, H.F. Kaspar, T. Yasumoto: Gymnodimine, a new marine toxin of unprecedented structure isolated from New Zealand oysters and the dinoflagellate, Gymnodinium sp., Tetrahedron Lett. 36(39), 7093–7096 (1995)CrossRefGoogle Scholar
  85. [37.85]
    S.Z. Zheng, F.L. Huang, S.C. Chen, X.F. Tan, J.B. Zuo, J. Peng, R.W. Xie: The isolation and bioactivities of pinnatoxin, Chin. J. Mar. Drugs 33(9), 33–35 (1990), in ChineseGoogle Scholar
  86. [37.86]
    N. Takada, N. Umemura, K. Suenaga, D. Uemura: Structural determination of pteriatoxins A, B and C, extremely potent toxins from the bivalve Pteria penguin, Tetrahedron Lett. 42(20), 3495–3497 (2001)CrossRefGoogle Scholar
  87. [37.87]
    K. Torigoe, M. Murata, T. Yasumoto: Prorocentrolide, a toxic nitrogenous macrocycle from a marine dinoflagellate, Prorocentrum lima, J. Am. Chem. Soc. 110, 7876–7877 (1988)CrossRefGoogle Scholar
  88. [37.88]
    T.M. Hu, A.S.W. de Freitas, J.M. Curtis, Y. Oshima, J.A. Walter, J.L.C. Wright: Isolation and structure of prorocentrolide B, a fast-acting toxin from Prorocentrum maculosum, J. Nat. Prod. 59(11), 1010–1014 (1996)CrossRefGoogle Scholar
  89. [37.89]
    C.-K. Lu, G.-H. Lee, R. Huang, H.-N. Chou: Spiro-prorocentrimine, a novel macrocyclic lactone from a benthic Prorocentrum sp. of Taiwan, Tetrahedron Lett. 42(9), 1713–1716 (2001)CrossRefGoogle Scholar
  90. [37.90]
    Y. Kishi: Complete structure of maitotoxin, Pure Appl. Chem. 70(2), 339–344 (1999)Google Scholar
  91. [37.91]
    M. Murata, H. Naoki, S. Matsunaga, M. Satake, T. Yasumoto: Structure and partial stereochemical assignments for maitotoxin, the most toxic and largest natural non-biopolymer, J. Am. Chem. Soc. 116(16), 7098–7107 (1994)CrossRefGoogle Scholar
  92. [37.92]
    M. Sasaki, N. Matsumori, T. Maruyama, T. Nonomura, M. Murata, K. Tachibana, T. Yasumoto: The complete structure of maitotoxin, Part I: Configuration of the C1-C14 side Chain, Angew. Chem. Int. Ed. Engl. 35(15), 1672–1675 (1996)CrossRefGoogle Scholar
  93. [37.93]
    M. Estacion, W.P. Schilling: Maitotoxin-induced membrane blebbing and cell death in bovine aortic endothelial cells, BMC Physiology 1, 2–12 (2001)CrossRefGoogle Scholar
  94. [37.94]
    K.K.W. Wang, R. Nath, K.J. Raser, I. Hajimohammadreza: Maitotoxin induces calpain activation in SH-SY5Y neuroblastoma cells and cerebrocortical cultures, Arch. Biochem. Biophys. 331(2), 208–214 (1996)CrossRefGoogle Scholar
  95. [37.95]
    M. Carrera, E. Garet, A. Barreiro, E. Garcés, D. Pérez, C. Guisande, A. González-Fernández: Generation of monoclonal antibodies for the specific immunodetection of the toxic dinoflagellate Alexandrium minutum Halim from Spanish waters, Harmful Algae 9, 272–280 (2010)CrossRefGoogle Scholar
  96. [37.96]
    A. González-Fernández, E. Garet Fonández, H. Kleivdal, C. Elliot, K. Campbell: Immunological methods for detection of toxic algae and phycotoxins: Immunofluorescence, ELISAS and other innovative techniques. In: New Trends in Marine and Freshwater Toxins: Food Safety Concerns, ed. by A.G. Cabado, J.M. Vieites (NovaScience, New York 2012) pp. 267–303, Chapter 9Google Scholar
  97. [37.97]
    L. Campbell, R.J. Olson, H.M. Sosik, A. Abraham, D.W. Henrichs, C.J. Hyatt, E.J. Buskey: First harmful Dinophysis (Dinophyceae, Dinophysiales) bloom in the US is revealed by automated imaging flow cytometry, J. Phycol. 46, 66–75 (2010)CrossRefGoogle Scholar
  98. [37.98]
    European Commission: Commission Regulation (EC): No 1244/2007 of 24 October 2007 amending Regulation (EC) No 2074/2005 as regards implementing measures for centain products of animal origin intended for human consumption and laying down specific rules on official controls for the inspection of meat, Off. J. Eur. Union L 281, 12–18 (2007)Google Scholar
  99. [37.99]
    Y. Zhou, Y.-S. Li, F.-G. Pan, Y.-Y. Zhang, S.-Y. Lu, H.-L. Ren, Z.-H. Li, Z.-S. Liu, J.-H. Zhang: Development of a new monoclonal antibody based direct competitive enzyme-linked immunosorbent assay for detection of brevetoxins in food samples, Food Chem. 118(2), 467–471 (2010)CrossRefGoogle Scholar
  100. [37.100]
    T. Tsumuraya, K. Takeuchi, S. Yamashita, I. Fujii, M. Hirama: Development of a monoclonal antibody against the left wing of ciguatoxin CTX1B: Thiol strategy and detection using a sandwich ELISA, Toxicon 60(3), 348–357 (2012)CrossRefGoogle Scholar
  101. [37.101]
    T.I. Tsumuraya, I. Fujii, M. Hirama: Production of monoclonal antibodies for sandwich immunoassay detection of Pacific ciguatoxins, Toxicon 56(5), 797–803 (2010)CrossRefGoogle Scholar
  102. [37.102]
    A. Sassolas, G. Catanante, A. Hayat, L.D. Stewart, C.T. Elliott, J.L. Marty: Improvement of the efficiency and simplification of ELISA tests for rapid and ultrasensitive detection of okadaic acid in shellfish, Food Control. 30(1), 144–149 (2013)CrossRefGoogle Scholar
  103. [37.103]
    A. Sassolas, A. Hayat, G. Catanante, J.-L. Marty: Detection of the marine toxin okadaic acid: Assessing seafood safety, Talanta 105, 306–316 (2013)CrossRefGoogle Scholar
  104. [37.104]
    M.M. Vdovenko, C. Hung, I.Y. Sakharov, F.-Y. Yu: Determination of okadaic acid in shellfish by using a novel chemiluminescent enzyme-linked immunosorbent assay method, Talanta 116, 343–346 (2013)CrossRefGoogle Scholar
  105. [37.105]
    E. Garet, A.G. Cabado, J.M. Vieites, Á. González-Fernández: Rapid isolation of single-chain antibodies by phage display technology directed against one of the most potent marine toxins: Palytoxin, Toxicon 55(8), 1519–1526 (2010)CrossRefGoogle Scholar
  106. [37.106]
    E. Garet, A. González-Fernández, J. Lago, J.M. Vieites, A.G. Cabado: Comparative evaluation of enzyme-linked immunoassay and reference methods for the detection of shellfish hydrophilic toxins in several presentations of seafood, Toxicon 58, 1410–1415 (2010)Google Scholar
  107. [37.107]
    M. Dechraoui Bottein, J. Maucher Fuquay, R. Munday, A.I. Selwood, R. van Ginkel, C.O. Miles, J.I. Loader, A.L. Wilkins, J.S. Ramsdell: Bioassays methods for detection of N-palmitoylbrevetoxin-B2 (BTX-B4), Toxicon 55, 497–506 (2010)CrossRefGoogle Scholar
  108. [37.108]
    J. Homola, E. Brynda, P. Tobiska, I. Tichy, J. Skvor: Optical biosensors using surface plasmon resonance, Proc. SPIE Photonics Devices Syst. 401, 6130–6135 (1999)Google Scholar
  109. [37.109]
    J. Abery: SPR technology increases efficiency for discovery and development, Biopharm. Int. 1 (2001)Google Scholar
  110. [37.110]
    R.C. Stevens, S.D. Soelberg, B.-T.L. Eberhart, S. Spencer, J.C. Wekell, T.M. Chinowsky, V.L. Trainer, C.E. Furlong: Detection of the toxin domoic acid from clam extracts using a portable surface plasmon resonance biosensor, Harmful Algae 6(2), 166–174 (2007)CrossRefGoogle Scholar
  111. [37.111]
    E.S. Fonfría, N. Vilariño, K. Campbell, C. Elliott, S.A. Haughey, B. Ben-Gigirey, J.M. Vieites, K. Kawatsu, L.M. Botana: Paralytic shellfish poisoning detection by surface plasmon resonance-based biosensors in shellfish matrixes, Anal. Chem. 79(16), 6303–6311 (2007)CrossRefGoogle Scholar
  112. [37.112]
    A.D. Taylor, J. Ladd, S. Etheridge, J. Deeds, S. Hall, S. Jiang: Quantitative detection of tetrodotoxin (TTX) by a surface plasmon resonance (SPR) sensor, Sens. Actuators B 130(1), 120–128 (2008)CrossRefGoogle Scholar
  113. [37.113]
    B.J. Yakes, S. Prezioso, S.A. Haughey, K. Campbell, C.T. Elliott, S.L. DeGrasse: An improved immunoassay for detection of saxitoxin by surface plasmon resonance biosensors, Sens. Actuators B 156(2), 805–811 (2011)CrossRefGoogle Scholar
  114. [37.114]
    K. Campbell, A.C. Huet, C. Charlier, C. Higgins, P. Delahaut, C.T. Elliott: Comparison of ELISA and SPR biosensor technology for the detection of paralytic shellfish poisoning toxins, J. Chromatogr. B 877(32), 4079–4089 (2009)CrossRefGoogle Scholar
  115. [37.115]
    K. Metfies, S. Huljic, M. Lange, L.K. Medlin: Electrochemical detection of the toxic dinoflagellate Alexandrium ostenfeldii with a DNA-biosensor, Biosens. Bioelectron. 20(7), 1349–1357 (2005)CrossRefGoogle Scholar
  116. [37.116]
    A. Hayat, L. Barthelmebs, J.-L. Marty: Enzyme-linked immunosensor based on super paramagnetic nanobeads for easy and rapid detection of okadaic acid, Anal. Chim. Acta 690(2), 248–252 (2011)CrossRefGoogle Scholar
  117. [37.117]
    R.B. Dominguez, A. Hayat, A. Sassolas, G.A. Alonso, R. Munoz, J.-L. Marty: Automated flow-through amperometric immunosensor for highly sensitive and on-line detection of okadaic acid in mussel sample, Talanta 99, 232–237 (2012)CrossRefGoogle Scholar
  118. [37.118]
    A. Hayat, L. Barthelmebs, A. Sassolas, J.-L. Marty: Development of a novel label-free amperometric immunosensor for the detection of okadaic acid, Anal. Chim. Acta 724, 92–97 (2012)CrossRefGoogle Scholar
  119. [37.119]
    T. Ikehara, S. Imamura, A. Yoshino, T. Yasumoto: PP2A inhibition assay using recombinant enzyme for rapid detection of okadaic acid and its analogs in shellfish, Toxins 2(1), 195–204 (2010)CrossRefGoogle Scholar
  120. [37.120]
    D.O. Mountfort, T. Suzuki, P. Truman: Protein phosphatase inhibition assay adapted for determination of total DSP in contaminated mussels, Toxicon 39(2/3), 383–390 (2001)CrossRefGoogle Scholar
  121. [37.121]
    G. Volpe, E. Cotroneo, D. Moscone, L. Croci, L. Cozzi, G. Ciccaglioni, G. Palleschi: A bienzyme electrochemical probe for flow injection analysis of okadaic acid based on protein phosphatase-2A inhibition: An optimization study, Anal. Biochem. 385(1), 50–56 (2009)CrossRefGoogle Scholar
  122. [37.122]
    H. Smienk, E. Dominguez, A. Otero, A.G. Cabado, J. Vieites: Quantitive determination of okadatic acid toxins group by a colorimetric phosphatase inhibition assay: Collaborative study, J. AOAC Int. 96(1), 77–85 (2013)CrossRefGoogle Scholar
  123. [37.123]
    European Council: (EC) CR (2005) Commission Regulation (EC) No 2074/2005 of 5 December 2005 laying down implementing measures for certain products under Regulation (EC) No 853/2004 of the European Parliament and of the Council and for the organisation of official controls under Regulation (EC) No 854/2004 of the European Parliament and of the Council and Regulation (EC) No 882/2004 of the European Parliament and of the Council, derogating from Regulation (EC) No 852/2004 of the European Parliament and of the Council and amending Regulations (EC) No 853/2004 and (EC) No 854/2004, Off. J. Eur. Union L 338, 27–59 (2005)Google Scholar
  124. [37.124]
    European Commission: Commision Regulation (EU): No 15/2011 of 10 January 2011 amending Regulation (EC) No 2074/2005 as regards testing methods for detecting marine biotoxins in live bivalve molluscs., vol. 11.1.2011, Off. J. Eur. Union 6, 3–6 (2011)Google Scholar
  125. [37.125]
    X. Zhang, Z. Zhang: Capillary electrophoresis-based immunoassay with electrochemical detection as rapid method for determination of saxitoxin and decarbamoylsaxitoxin in shellfish samples, J. Food Compos. Anal. 28(1), 61–68 (2012)CrossRefGoogle Scholar
  126. [37.126]
    F. Fournel, E. Baco, M. Mamani-Matsuda, M. Degueil, B. Bennetau, D. Moynet, D. Mossalayi, L. Vellutini, J.P. Pillot, C. Dejous, D. Rebière: Love wave biosensor for real-time detection of okadaic acid as DSP phycotoxin, Sens. Actuators B 170, 122–128 (2012)CrossRefGoogle Scholar
  127. [37.127]
    M.R. Vieytes, A.G. Cabado, A. Alfonso, C. Louzao, A. Botana, L. Botana: Solid-phase radioreceptor assay for paralytic shellfish toxins, Anal. Biochem. 211, 87–93 (1993)CrossRefGoogle Scholar
  128. [37.128]
    G.J. Doucette, M.M. Logan, J.S. Ramsdell, F.M. Van Dolah: Development and preliminary validation of a microtiter plate-based receptor binding assay for paralytic shellfish poisoning toxins, Toxicon 35(5), 625–636 (1997)CrossRefGoogle Scholar
  129. [37.129]
    G. Usup, C.P. Leaw, M.-Y. Cheah, A. Ahmad, B.K. Ng: Analysis of paralytic shellfish poisoning toxin congeners by a sodium channel receptor binding assay, Toxicon 44(1), 37–43 (2004)CrossRefGoogle Scholar
  130. [37.130]
    G.J. Doucette, C.L. Powell, E.U. Do, C.Y. Byon, F. Cleves, S.G. McClain: Evaluation of 11-[3H]-tetrodotoxin use in a heterologous receptor binding assay for PSP toxins, Toxicon 38(11), 1465–1474 (2000)CrossRefGoogle Scholar
  131. [37.131]
    C.L. Powell, G.J. Doucette: A receptor binding assay for paralytic shellfish poisoning toxins: Recent advances and applications, Nat. Toxins 7(6), 393–400 (1999)CrossRefGoogle Scholar
  132. [37.132]
    B.A. Suárez-Isla: Paralytic shellfish toxins -pharmacology, and toxicology biological detection methods. In: Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, ed. by L.A. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 197–205CrossRefGoogle Scholar
  133. [37.133]
    F.M. Van Dolah, S.E. Fuego, T.A. Leighfield, C.M. Mikulsk, G.J. Doucette: Determination of paralytic shellfish toxins in shellfish by receptor binding assay: Collaborative study, J. AOAC Int. 95(3), 795–812 (2012)CrossRefGoogle Scholar
  134. [37.134]
    V.L. Trainer, D.G. Baden, W.A. Catterall: Detection of marine toxins using recontituted sodium channels, J. AOAC Int. 78, 570–573 (1995)Google Scholar
  135. [37.135]
    R.A. Edwards, A.M. Stuart, D.G. Baden: Brevetoxin binding in three phylogenetically diverse vertebrates, Toxic Marine Phytoplankton, 4th Int. Conf., Lund, Swedan, ed. by E. Graneli (Elsevier, New York 1990), Illus. Maps 290–293Google Scholar
  136. [37.136]
    V.L. Trainer, D.G. Baden: High affinity binding of red tide neurotoxins to marine mammal brain, Aquat. Toxicol. 46, 139–148 (1999)CrossRefGoogle Scholar
  137. [37.137]
    M.L.J. Twiner, M.-Y. Bottein Dechraoui, Z. Wang, C.M. Mikulski, M.S. Henry, R.H. Pierce, G.J. Doucette: Extraction and analysis of lipophilic brevetoxins from the red tide dinoflagellate Karenia brevis, Anal. Biochem. 369(1), 128–135 (2007)CrossRefGoogle Scholar
  138. [37.138]
    M. Chinain, H. Darius, A. Ung, M. Fouc, T. Revel, P. Cruchet, S. Pauillac, D. Laurent: Ciguatera risk management in French Polynesia: The case study of Raivavae Island (Australes Archipelago), Toxicon 56(5), 674–690 (2010)CrossRefGoogle Scholar
  139. [37.139]
    H.T. Darius, D. Ponton, T. Revel, P. Cruchet, A. Ung, M.T. Fouc, M. Chinain: Ciguatera risk assessment in two toxic sites of French Polynesia using the receptor-binding assay, Toxicon 50, 612–626 (2007)CrossRefGoogle Scholar
  140. [37.140]
    F.M. Van Dolah, T.A. Leighfield, B.L. Haynes, D.R. Hampson, J.S. Ramsdell: A microplate receptor assay for the amnesic shellfish poisoning toxin, domoic acid, utilizing a cloned glutamate receptor, Anal. Biochem. 245(1), 102–105 (1997)CrossRefGoogle Scholar
  141. [37.141]
    K.A. Baugh, S. Spencer, J.C. Wekell, V.L. Trainer, K.A. Steidinger, J.H. Landsberg, C.R. Tomas, G.A. Vargo: An alternative method for domoic acid determination in seawater particulates: A receptor binding assay using glutamate dehydrogenase. In: Harmful Algae 2002. Florida Fish and Wildlife Conservation Commission, (Florida Institute of Oceanography, and Intergovernmental Oceanographic Commission of UNESCO, Paris 2004)Google Scholar
  142. [37.142]
    T. Yasumoto: Search for ciguatoxin producing clones of Gambierdiscus toxicus on Okinawan coastal reef, Ciguatera and Related Biotoxins Workshop, New Caledoria, France, 2000 (Elsevier, Paris 2008)Google Scholar
  143. [37.143]
    D.M. Anderson, A.D. Cembella, G.M. Hallegraeff: Progress in understanding harmful algal blooms: Paradigm shifts and new technologies for research, monitoring, and management, Annu. Rev. Mar. Sci. 4, 143–176 (2012)CrossRefGoogle Scholar
  144. [37.144]
    A. Penna, C. Battocchi, E. Garcés, S. Anglès, E. Cucchiari, C. Totti, A. Kremp, C. Satta, M. Grazia Giacobbe, I. Bravo: Detection of microalgal resting cysts in European coastal sediments using a PCR-based assay, Deep Sea Res. Part II 57(3), 288–300 (2010)CrossRefGoogle Scholar
  145. [37.145]
    L. Galluzzi, A. Cegna, S. Casabianca, A. Penna, N. Saunders, M. Magnani: Development of an oligonucleotide microarray for the detection and monitoring of marine dinoflagellates, J. Microbiol. Methods 84(2), 234–242 (2011)CrossRefGoogle Scholar
  146. [37.146]
    M.W. Vandersea, S.R. Kibler, W.C. Holland, P.A. Tester, T.F. Schultz, M.A. Faust, M.J. Holmes, M. Chinain, R.W. Litaker: Development of semi-quantitative PCR assays for the detection and enumeration of Gambierdiscus species (Gonyaulacales, Dinophyceae), J. Phycol. 48(4), 902–915 (2011)CrossRefGoogle Scholar
  147. [37.147]
    T. Nishimura, S. Sato, W. Tawong, H. Sakanari, K. Uehara, M.M.R. Shah, S. Suda, T. Yasumoto, Y. Taira, H. Yamaguchi: Genetic diversity and distribution of the ciguatera-causing dinoflagellate Gambierdiscus spp. (Dinophyceae) in coastal areas of Japan, PLoS ONE 8(4), e60882 (2013)CrossRefGoogle Scholar
  148. [37.148]
    T.A. Rynearson, B. Palenik: Learning to read the oceans: Genomics of marine phytoplankton, Adv. Mar. Biol. 60, 1–39 (2011)CrossRefGoogle Scholar
  149. [37.149]
    B. Palenik, J. Grimwood, A. Aerts, P. Rouze, A. Salamov, N. Putnam, C. Dupont, R. Jorgensen, E. Derelle, S. Rombauts, K. Zhou, R. Otillar, S.S. Merchant, S. Podell, T. Gaasterland, C. Napoli, K. Gendler, A. Manuell, V. Tai, O. Vallon, G. Piganeau, S. Jancek, M. Heijde, K. Jabbari, C. Bowler, M. Lohr, S. Robbens, G. Werner, I. Dubchak, G.J. Pazour, Q. Ren, I. Paulsen, C. Delwiche, J. Schmutz, D. Rokhsar, Y. Van de Peer, H. Moreau, I.V. Grigoriev: The tiny eukaryote Ostreococcus provides genomic insights into the paradox of plankton speciation, Proc. Natl. Acad. Sci. USA 104(18), 7705–7710 (2007)CrossRefGoogle Scholar
  150. [37.150]
    C.J. Gobler, D.L. Berry, S.T. Dyhrman, S.W. Wilhelm, A. Salamov, A.V. Lobanov, Y. Zhang, J.L. Collier, L.L. Wurch, A.B. Kustka, B.D. Dill, M. Shah, N.C. VerBerkmoes, A. Kuo, A. Terry, J. Pangilinan, E.A. Lindquist, S. Lucas, I.T. Paulsen, T.K. Hattenrath-Lehmann, S.C. Talmage, E.A. Walker, F. Koch, A.M. Burson, M.A. Marcoval, Y.-Z. Tang, G.R. LeCleir, K.J. Coyne, G.M. Berg, E.M. Bertrand, M.A. Saito, V.N. Gladyshev, I.V. Grigoriev: Niche of harmful alga Aureococcus anophagefferens revealed through ecogenomics, Proc. Natl. Acad. Sci. USA 108(11), 4352–4357 (2011)CrossRefGoogle Scholar
  151. [37.151]
    E.V. Armbrust, J.A. Berges, C. Bowler, B.R. Green, D. Martinez, N.H. Putnam, S.G. Zhou, A.E. Allen, K.E. Apt, M. Bechner, M.A. Brzezinski, B.K. Chaal, A. Chiovitti, A.K. Davis, M.S. Demarest, J.C. Detter, T. Glavina, D. Goodstein, M.Z. Hadi, U. Hellsten, M. Hildebrand, B.D. Jenkins, J. Jurka, V.V. Kapitonov, N. Kroger, W.W.Y. Lau, T.W. Lane, F.W. Larimer, J.C. Lippmeier, S. Lucas, M. Medina, A. Montsant, M. Obornik, M.S. Parker, B. Palenik, G.J. Pazour, P.M. Richardson, T.A. Rynearson, M.A. Saito, D.C. Schwartz, K. Thamatrakoln, K. Valentin, A. Vardi, F.P. Wilkerson, D.S. Rokhsar: The genome of the diatom Thalassiosira pseudonana: Ecology, evolution, and metabolism, Science 306(5693), 79–86 (2004)CrossRefGoogle Scholar
  152. [37.152]
    A.Z. Worden, J.-H. Lee, T. Mock, P. Rouze, M.P. Simmons, A.L. Aerts, A.E. Allen, M.L. Cuvelier, E. Derelle, M.V. Everett, E. Foulon, J. Grimwood, H. Gundlach, B. Henrissat, C. Napoli, S.M. McDonald, M.S. Parker, S. Rombauts, A. Salamov, P. Von Dassow, J.H. Badger, P.M. Coutinho, E. Demir, I. Dubchak, C. Gentemann, W. Eikrem, J.E. Gready, U. John, W. Lanier, E.A. Lindquist, S. Lucas, K.F.X. Mayer, H. Moreau, F. Not, R. Otillar, O. Panaud, J. Pangilinan, I. Paulsen, B. Piegu, A. Poliakov, S. Robbens, J. Schmutz, E. Toulza, T. Wyss, A. Zelensky, K. Zhou, E.V. Armbrust, D. Bhattacharya, U.W. Goodenough, Y. Van de Peer, I.V. Grigoriev: Green evolution and dynamic adaptations revealed by genomes of the marine picoeukaryotes micromonas, Science 324(5924), 268–272 (2009)CrossRefGoogle Scholar
  153. [37.153]
    A.E. Allen, J. LaRoche, U. Maheswari, M. Lommer, N. Schauer, P.J. Lopez, G. Finazzi, A.R. Fernie, C. Bowler: Whole-cell response of the pennate diatom Phaeodactylum tricornutum to iron starvation, Proc. Natl. Acad. Sci. USA 105(30), 10438–10443 (2008)CrossRefGoogle Scholar
  154. [37.154]
    T. Mock, M.P. Samanta, V. Iverson, C. Berthiaume, M. Robison, K. Holtermann, C. Durkin, S.S. BonDurant, K. Richmond, M. Rodesch, T. Kallas, E.L. Huttlin, F. Cerrina, M.R. Sussmann, E.V. Armbrust: Whole-genome expression profiling of the marine diatom Thalassiosira pseudonana identifies genes involved in silicon bioprocesses, Proc. Natl. Acad. Sci. USA 105(5), 1579–1584 (2008)CrossRefGoogle Scholar
  155. [37.155]
    P. von Dassow, H. Ogata, I. Probert, P. Wincker, C. Da Silva, S. Audic, J.-M. Claverie, C. de Vargas: Transcriptome analysis of functional differentiation between haploid and diploid cells of Emiliania huxleyi, a globally significant photosynthetic calcifying cell, Genome Biol. 10(10), R114 (2009)CrossRefGoogle Scholar
  156. [37.156]
    M.L. Cuvelier, A.E. Allen, A. Monier, J.P. McCrow, M. Messie, S.G. Tringe, T. Woyke, R.M. Welsh, T. Ishoey, J.-H. Lee, B.J. Binder, C.L. DuPont, M. Latasa, C. Guigand, K.R. Buck, J. Hilton, M. Thiagarajan, E. Caler, B. Read, R.S. Lasken, F.P. Chavez, A.Z. Worden: Targeted metagenomics and ecology of globally important uncultured eukaryotic phytoplankton, Proc. Natl Acad. Sci. USA 107(33), 14679–14684 (2010)CrossRefGoogle Scholar
  157. [37.157]
    K.B. Andree, M. Fernández-Tejedor, L.M. Elandaloussi, S. Quijano-Scheggia, N. Sampedro, E. Garcés, J. Camp, J. Diogène: Quantitative PCR coupled with melt curve analysis for detection of selected Pseudo-nitzschia spp. (Bacillariophyceae) from the northwestern Mediterranean Sea, Appl. Environ. Microbiol. 77(5), 1651–1659 (2011)CrossRefGoogle Scholar
  158. [37.158]
    A. Penna, M. Vila, S. Fraga, M.G. Giacobbe, F. Andreoni, P. Riobó, C. Vernesi: Characterization of Ostreopsis and Coolia (Dinophyceae) isolates in the western Mediterranean Sea based on morphology, toxicity and internal transcribed spacer 5.8S rDNA sequences, J. Phycol. 41(1), 212–225 (2005)CrossRefGoogle Scholar
  159. [37.159]
    B. Genovesi, M.-S. Shin-Grzebyk, D. Grzebyk, M. Laabir, P.-A. Gagnaire, A. Vaquer, A. Pastoureaud, B. Lasserre, Y. Collos, P. Berrebi: Assessment of cryptic species diversity within blooms and cyst bank of the Alexandrium tamarense complex (Dinophyceae) in a Mediterranean lagoon facilitated by semi-multiplex PCR, J. Plankton Res. 33(3), 405–414 (2011)CrossRefGoogle Scholar
  160. [37.160]
    D.G. Borkman, T.J. Smayda, C.R. Tomas, R. York, W. Strangman, J. Wright: Toxic Alexandrium peruvianum (Balech and de Mendiola) Balech and Tangen in Narragansett Bay, Rhode Island (USA), Harmful Algae 19, 92–100 (2012)CrossRefGoogle Scholar
  161. [37.161]
    F. Perini, A. Casabianca, C. Battocchi, S. Accoroni, C. Totti, A. Penna: New approach using the real-time PCR method for estimation of the toxic marine dinoflagellate Ostreopsis cf. ovata in marine environment, PLoS One 6(3), e17699 (2011)CrossRefGoogle Scholar
  162. [37.162]
    S. Nagai: Development of a multiplex PCR assay for simultaneous detection of six Alexandrium species (Dinophyceae), J. Phycol. 47(3), 703–708 (2011)CrossRefGoogle Scholar
  163. [37.163]
    J. Al-Tebrineh, L.A. Pearson, S.A. Yasar, B.A. Neilan: A multiplex PCR targeting hepato-and neurotoxigenic cyanobacteria of global significance, Harmful Algae 15, 19–25 (2012)CrossRefGoogle Scholar
  164. [37.164]
    M.-È. Garneau, A. Schnetzer, P.D. Countway, A.C. Jones, E.L. Seubert, D.A. Caron: Examination of the seasonal dynamics of the toxic dinoflagellate Alexandrium catenella at Redondo Beach, California, by quantitative PCR, Appl. Environ. Microbiol. 77(21), 7669–7680 (2011)CrossRefGoogle Scholar
  165. [37.165]
    S.A. Murray, M. Wiese, A. Stuken, S. Brett, R. Kellmann, G. Hallegraeff, B.A. Neilan: sxtA-Based quantitative molecular assay to identify saxitoxin-producing harmful algal blooms in marine waters, Appl. Environ. Microbiol. 77(19), 7050–7057 (2011)CrossRefGoogle Scholar
  166. [37.166]
    A. Penna, E. Bertozzini, C. Battocchi, L. Galluzzi, M.G. Giacobbe, M. Vila, E. Garces, A. Luglié: M. Magnani: Monitoring of HAB species in the Mediterranean Sea through molecular methods, J. Plankton Res. 29(1), 19–38 (2007)CrossRefGoogle Scholar
  167. [37.167]
    S.M. Dittami, C. Proux, S. Rousvoal, A.F. Peters, J.M. Cock, J.-Y. Coppee, C. Boyen, T. Tonon: Microarray estimation of genomic inter-strain variability in the genus Ectocarpus (Phaeophyceae), BMC Mol. Biol. 1, 2 (2011)CrossRefGoogle Scholar
  168. [37.168]
    J.U. Kegel, Y. Del Amo, L. Costes, L.K. Medlin: Testing a microarray to detect and monitor toxic microalgae in Arcachon Bay in France, Microarrays 2(1), 1–23 (2013)CrossRefGoogle Scholar
  169. [37.169]
    S.M. Dittami, Y. Pazos, M. Laspra, L.K. Medlin: Microarray testing for the presence of toxic algae monitoring programme in Galicia (NW Spain), Environ. Sci. Pollut. Res. 20(10), 6778–6793 (2013)CrossRefGoogle Scholar
  170. [37.170]
    A. de Bruin, B.W. Ibelings, E. Van Donk: Molecular techniques in phytoplankton research: From allozyme electrophoresis to genomics, Hydrobiologia 491(1–3), 47–63 (2003)CrossRefGoogle Scholar
  171. [37.171]
    T.I. McLean: Eco-omics: A review of the application of genomics, transcriptomics, and proteomics for the study of the ecology of harmful Algae, Microb. Ecol. 65, 901–915 (2013)CrossRefGoogle Scholar
  172. [37.172]
    A. Jamers, R. Blust, W. De Coen: Omics in algae: Paving the way for a systems biological understanding of algal stress phenomena?, Aquat. Toxicol. 92(3), 114–121 (2009)CrossRefGoogle Scholar
  173. [37.173]
    I. Yang, U. John, S. Beszteri, G. Gloeckner, B. Krock, A. Goesmann, A.D. Cembella: Comparative gene expression in toxic versus non-toxic strains of the marine dinoflagellate Alexandrium minutum, BMC Genomics 11, 248 (2010)CrossRefGoogle Scholar
  174. [37.174]
    N. Jaeckisch, I. Yang, S. Wohlrab, G. Glöckner, J. Kroymann, H. Vogel, A. Cembella, U. John: Comparative genomic and transcriptomic characterization of the toxigenic marine dinoflagellate Alexandrium ostenfeldii, PLoS ONE 6(12), e28012 (2011)CrossRefGoogle Scholar
  175. [37.175]
    B.L. Nunn, A.T. Timperman: Marine proteomics, Mar. Ecol. Prog. Ser. 332, 281–289 (2007)CrossRefGoogle Scholar
  176. [37.176]
    L.L. Chan, I.J. Hodgkiss, S. Lu, S.C.L. Lo: Use of two-dimensional gel electrophoresis proteome reference maps of dinoflagellates for species recognition of causative agents of harmful algal blooms, Proteomics 4(1), 180–192 (2004)CrossRefGoogle Scholar
  177. [37.177]
    L.L. Chan, I.J. Hodgkiss, J.M.F. Wan, J.H.K. Lum, A.S.C. Mak, W.H. Sit, S.C.L. Lo: Proteomic study of a model causative agent of harmful algal blooms, Prorocentrum triestinum II: The use of differentially expressed protein profiles under different growth phases and growth conditions for bloom prediction, Proteomics 4(10), 3214–3226 (2004)CrossRefGoogle Scholar
  178. [37.178]
    L. Wang, S.A. Shankarappa, R. Tong, J.B. Ciolino, J.H. Tsui, H.H. Chiang, D.S. Kohane: Topical drug formulations for prolonged corneal anesthesia, Cornea 32(7), 1040–1045 (2013)CrossRefGoogle Scholar
  179. [37.179]
    D.M. Anderson, A.D. Cembella, G.M. Hallegraeff: Progress in understanding harmful algal blooms: Paradigm shifts and new technologies for research, monitoring, and management, Annu. Rev. Mar. Sci. 4, 143–176 (2012)CrossRefGoogle Scholar
  180. [37.180]
    O. Fiehn: Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks, Comp. Funct. Genomics 2(3), 155–168 (2001)CrossRefGoogle Scholar
  181. [37.181]
    A. Ianora, G. Romano, Y. Carotenuto, F. Esposito, V. Roncalli, I. Buttino, A. Miralto: Impact of the diatom oxylipin 15S-HEPE on the reproductive success of the copepod Temora stylifera, Hydrobiologia 666(1), 265–275 (2011)CrossRefGoogle Scholar
  182. [37.182]
    A.R. Fernie, T. Obata, A.E. Allen, W.L. Araujo, C. Bowler: Leveraging metabolomics for functional investigations in sequenced marine diatoms, Trends Plant Sci. 17(7), 395–403 (2012)CrossRefGoogle Scholar
  183. [37.183]
    P. Hess: Specific, Quantitative and metabolomic techniques for the analysis of marine biotoxins, Paper presented at the Marine and Freshwater Toxins Analysis, 4th H. Symp. AOAC Task Force Meed. Baiona (2013)Google Scholar
  184. [37.184]
    D.-Z. Wang: Neurotoxins from marine dinoflagellates: A brief review, Mar. Drugs 6(2), 349–371 (2008)CrossRefGoogle Scholar
  185. [37.185]
    D.-Z. Wang, Y. Gao, L. Lin, H.-S. Hong: Comparative proteomic analysis reveals proteins putatively involved in toxin biosynthesis in the marine dinoflagellate Alexandrium catenella, Mar. Drugs 11(1), 213–232 (2013)CrossRefGoogle Scholar
  186. [37.186]
    M. Wiese, P.M. D'Agostino, T.K. Mihali, M.C. Moffitt, B.A. Neilan: Neurotoxic alkaloids: Saxitoxin and its analogs, Mar. Drugs 8(7), 2185–2211 (2010)CrossRefGoogle Scholar
  187. [37.187]
    M.R. Watters: Marine neurotoxins as a starting point to drugs. In: Seafood and Freshwater Toxins: Pharmacology, Physiology and Detection, ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 889–896CrossRefGoogle Scholar
  188. [37.188]
    K.D. Cusick, G.S. Sayler: An Overview on the marine neurotoxin, saxitoxin: Genetics, molecular targets, methods of detection and ecological functions, Mar. Drugs 11(4), 991–1018 (2013)CrossRefGoogle Scholar
  189. [37.189]
    J.J. Fernández, M.L. Candenas, M.L. Souto, M.M. Trujillo, M. Norte: Okadaic acid, useful tool for studying cellular processes, Curr. Med. Chem. 9, 229–262 (2002)CrossRefGoogle Scholar
  190. [37.190]
    H. Fujiki, M. Suganuma: Unique features of the okadaic acid activity on class of tumor promoters, J. Cancer Res. Clin. Oncol. 125, 150–155 (1999)CrossRefGoogle Scholar
  191. [37.191]
    M.M. Islam, S. Begum, L. Lin, A. Okamura, M. Du, S. Fujimura: Synergistic cytotoxic effect between serine-threonine phosphatase inhibitors and 5-fluorouracil: A novel concept for modulation of cytotoxic effect, Cancer Chemother. Pharmacol. 49, 111–118 (2002)CrossRefGoogle Scholar
  192. [37.192]
    V. Valdiglesias, J. Méndez, E. Pásaro, E. Cemeli, D. Anderson, B. Laffon: Assessment of okadaic acid effects on cytotoxicity, DNA damage and DNA repair in human cells, Mutation Res. Fundam. Mol. Mech. Mutagen. 689(1/2), 74–79 (2010)CrossRefGoogle Scholar
  193. [37.193]
    J. He, Y. Yang, H. Xu, X. Zhang, X.M. Li: Olanzapine attenuates the okadaic acid-induced spatial memory impairment and hippocampal cell death in rats, Neuropsychopharmacology 30, 1511–1520 (2005)CrossRefGoogle Scholar
  194. [37.194]
    A.G. Cabado, F. Leira, J.M. Vieites, M.R. Vieytes, L. Botana: Caspase-8 activation initiates okadaic acid-induced apoptosis in neuroblastoma. In: Molluscan Shellfish Safety, ed. by B.R.A. Villalba, J.L. Romalde, R. Beiras (Consellería de Pesca e Asuntos Marítimos da Xunta de Galicia and Intergovernmental Oceanographic Commission of UNESCO, Santiago de Compostela 2003) pp. 107–117Google Scholar
  195. [37.195]
    J. Lago, F. Santaclara, J.M. Vieites, A.G. Cabado: Collapse of mitochondrial membrane potential and caspases activation are early events in okadaic acidtreated Caco-2 cells, Toxicon 46(5), 579–586 (2005)CrossRefGoogle Scholar
  196. [37.196]
    A. Franchini, D. Malagoli, E. Ottaviani: Targets and effects of yessotoxin, okadaic acid and palytoxin: A differential review, Mar. Drugs 8(3), 658–677 (2010)CrossRefGoogle Scholar
  197. [37.197]
    V. Valdiglesias, B. Laffon, E. Pásaro, E. Cemeli, D. Anderson, J. Méndez: Induction of oxidative DNA damage by the marine toxin okadaic acid depends on human cell type, Toxicon 57(6), 882–888 (2011)CrossRefGoogle Scholar
  198. [37.198]
    V. Valdiglesias, B. Laffon, E. Pásaro, J. Méndez: Evaluation of okadaic acid-induced genotoxicity in human cells using the micronucleous test and gamma H2AX analysis, J. Toxicol. Environ. Health Part A: Current Issues 74(15/16), 980–992 (2011)CrossRefGoogle Scholar
  199. [37.199]
    V. Valdiglesias, B. Laffon, E. Pásaro, J. Méndez: Okadaic acid induces morphological changes, apoptosis and cell cycle alterations in different human cell types, J. Environ. Monit. 13(6), 1831–1840 (2011)CrossRefGoogle Scholar
  200. [37.200]
    C. Vale, L.M. Botana: Marine toxins and the cytoskeleton: Okadaic acid and dinophysistoxins, FEBS Journal 275(24), 6060–6066 (2008)CrossRefGoogle Scholar
  201. [37.201]
    F. Leira, C. Alvarez, J.M. Vieites, M.R. Vieytes, L.M. Botana: Characterization of distinct apoptotic changes induced by okadaic acid and yessotoxin in the BE(2)-M17 neuroblastoma cell line, Toxicol. In Vitro 16(1), 23–31 (2002)CrossRefGoogle Scholar
  202. [37.202]
    A.G. Cabado, F. Leira, M.R. Vieytes, J.M. Vieites, L.M. Botana: Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells, Arch. Toxicol. 78, 74–85 (2005)CrossRefGoogle Scholar
  203. [37.203]
    F. Santaclara, J. Lago, J.M. Vieites, A.G. Cabado: Effect of okadaic acid on integrins and structural proteins in BE(2)-M17 cells, Arch. Toxicol. 79(10), 582–586 (2005)CrossRefGoogle Scholar
  204. [37.204]
    A. Franchini, D. Malagoli, E. Ottaviani: Targets and effects of yessotoxin, okadaic acid and palytoxin: A differential review, Mar. Drugs 8(3), 658–677 (2010)CrossRefGoogle Scholar
  205. [37.205]
    C. Lamas, I. Valverde, J. Lago, J.M. Vieites, A.G. Cabado: In vitro evaluation of apoptotic markers triggered by PTX-2 in Caco-2 and neuroblastoma cells, Egypt. J. Nat. Toxins 3, 17–33 (2006)Google Scholar
  206. [37.206]
    C. Lamas, I. Valverde, J. Lago, J.M. Vieites, A.G. Cabado: Comparison between cytotoxic effects induced by PTX-2 in vitro in two human cell lines, Egypt. J. Nat. Toxins 3, 1–16 (2006)Google Scholar
  207. [37.207]
    Z.H. Zhou, M. Komiyama, K. Terao, Y. Shimada: Effects of pectenotoxin-1 on liver cells in vitro, Nat. Toxins 2, 132–135 (1994)CrossRefGoogle Scholar
  208. [37.208]
    B. Espiña, J.A. Rubiolo: Marine toxins and the cytoskeleton: Pectenotoxins, unusual macrolides that disrupt actin, FEBS Journal 275(24), 6082–6088 (2008)CrossRefGoogle Scholar
  209. [37.209]
    H.D. Chae, T.S. Choi, B.M. Kim, J.H. Jung, Y.J. Bang, D.Y. Shin: Oocyte-based screening of cytokinesis inhibitors and identification of pectenotoxin-2 that induces Bim/Bax-mediated apoptosis in p53-deficient tumors, Oncogene 24, 4813–4819 (2005)CrossRefGoogle Scholar
  210. [37.210]
    N. Vilariño, B. Espina: Pharmacology of pectenotoxins. In: Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 361–380Google Scholar
  211. [37.211]
    T. Yasumoto, M. Murata, Y. Oshima, G.K. Matsumoto, J. Clardy: Diarrhetic shellfish poisoning. In: Seafood Toxins, ed. by E.P. Ragelis (American Chemical Society, Washington 1984) pp. 207–214CrossRefGoogle Scholar
  212. [37.212]
    European Union Reference Laboratory for Marine Biotoxins: EU Harmonised Standard Operating Procedure for detection of lipophilic toxins by mouse bioassay (2009), pp. 1–14Google Scholar
  213. [37.213]
    European Food Safety Authority: Opinion of the Scientific Panel on Contaminants in the Food chain on a request from the European Commission on marine biotoxins in shellfish – yessotoxin group, EFSA Journal 907, 1–62 (2008)Google Scholar
  214. [37.214]
    K. Terao, E. Ito, M. Oarada, M. Murata, T. Yasumoto: Histopathological studies on experimental marine toxin poisoning–5. The effects in mice of yessotoxin isolated from Patinopecten yessoensis and of a desulfated derivative, Toxicon 28, 1095–1104 (1990)CrossRefGoogle Scholar
  215. [37.215]
    A. Franchini, E. Marchesini, R. Poletti, E. Ottaviani: Acute toxic effect of the algal yessotoxin on Purkinje cells from the cerebellum of Swiss CD1 mice, Toxicon 43, 347–352 (2004)CrossRefGoogle Scholar
  216. [37.216]
    A. Alfonso, L. de la Rosa, M.R. Vieytes, T. Yasumoto, L.M. Botana: Yessotoxin a novel phycotoxin, activates phosphodiesterase activity. Effect of yessotoxin on cAMP levels in human lymphocytes, Biochem. Pharmacol. 65, 193–208 (2003)CrossRefGoogle Scholar
  217. [37.217]
    A. Tubaro, V. Dell'Ovo, S. Sosa, C. Florio: Yessotoxins: A toxicological overview, Toxicon 56(2), 163–172 (2010)CrossRefGoogle Scholar
  218. [37.218]
    A. Alfonso: Yessotoxins, pharmacology and mechanism of action: Biological detection. In: Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 315–327CrossRefGoogle Scholar
  219. [37.219]
    A. Perez-Gomez, A. Ferrero-Gutierrez, A. Novelli, J.M. Franco, B. Paz, M.T. Fernández-Sánchez: Potent neurotoxic action of the shellfish biotoxin yessotoxin on cultured cerebellar neurons, Toxicol. Sci. 90(1), 168–177 (2006)CrossRefGoogle Scholar
  220. [37.220]
    F. Leira, C. Alvarez, A.G. Cabado, J.M. Vieites, M.R. Vieytes, L.M. Botana: Development of a F actin-based live-cell fluorimetric microplate assay for diarrhetic shellfish toxins, Anal. Biochem. 317, 129–135 (2003)CrossRefGoogle Scholar
  221. [37.221]
    I.R. Ares, M.C. Louzao, M.R. Vieytes, T. Yasumoto, L.M. Botana: Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins, J. Exp. Biol. 208(22), 4345–4354 (2005)CrossRefGoogle Scholar
  222. [37.222]
    G. Ronzitti, F. Callegari, C. Malaguti, G.P. Rossini: Selective disruption of the E-cadherin-catenin system by an algal toxin, Br. J. Cancer 90, 1100–1107 (2004)CrossRefGoogle Scholar
  223. [37.223]
    F. Callegari, S. Sosa, S. Ferrari, M.R. Soranzo, S. Pierotti, T. Yasumoto, A. Tubaro, G.P. Rossini: Oral administration of yessotoxin stabilizes E-cadherin in mouse colon, Toxicology 227, 145–155 (2006)CrossRefGoogle Scholar
  224. [37.224]
    M.S. Korsnes, A. Espenes: Yessotoxin as an apoptotic inducer, Toxicon 57(7/8), 947–958 (2011)CrossRefGoogle Scholar
  225. [37.225]
    L.M. Botana, A. Alfonso, M.R. Vieytes, M.I. Loza-Garcia: Therapeutic use of yessotoxins as human tumor cell growth inhibitors, European Patent EP1875906 (2008)Google Scholar
  226. [37.226]
    P. Ciminiello, E. Fattorusso: Yessotoxins chemistry, metabolism and chemical analysis. In: Seafood and Freshwater Toxins. Pharmacology, Physiology and Detection, ed. by L.M. Botana (Taylor Francis, Boca Raton 2008) pp. 287–314CrossRefGoogle Scholar
  227. [37.227]
    S. Ferrari, P. Ciminiello, C. Dell'Aversano, M. Forino, C. Malaguti, A. Tubaro, R. Poletti, T. Yasumoto, E. Fattorusso, G.P. Rossini: Structure–activity relationships of yessotoxins in cultured cells, Chem. Res. Toxicol. 17, 1251–1257 (2004)CrossRefGoogle Scholar
  228. [37.228]
    M.J. Pazos, A. Alfonso, M.R. Vieytes, T. Yasumoto, L.M. Botana: Kinetic analysis of the interaction between yessotoxin and analogues and immobilized phosphodiesterases using a resonant mirror optical biosensor, Chem. Res. Toxicol. 18, 1155–1160 (2005)CrossRefGoogle Scholar
  229. [37.229]
    A. Alfonso, Y. Román, M.R. Vieytes, K. Ofuji, M. Satake, T. Yasumoto, L.M. Botana: Azaspiracid-4 inhibits Ca${}^{{2+}}$ entry by stored operated channels in human T lymphocytes, Biochem. Pharmacol. 69(11), 1627–1636 (2005)CrossRefGoogle Scholar
  230. [37.230]
    A. Alfonso, M.R. Vieytes, K. Ofuji, M. Satake, K.C. Nicolaou, M.O. Frederick, L.M. Botana: Azaspiracids modulate intracellular pH levels in human lymphocytes, Biochem. Biophys. Res. Commun. 346(3), 1091–1099 (2006)CrossRefGoogle Scholar
  231. [37.231]
    Y. Román, A. Alfonso, M.C. Louzao, L.A. de la Rosa, F. Leira, J.M. Vieites, M.R. Vieytes, K. Ofuji, M. Satake, T. Yasumoto, L.M. Botana: Azaspiracid-1, a potent, nonapoptotic new phycotoxin with several cell targets, Cell Signal. 14, 703–716 (2002)CrossRefGoogle Scholar
  232. [37.232]
    Y. Román, A. Alfonso, M.R. Vieytes, K. Ofuji, M. Satake, T. Yasumoto, L.M. Botana: Effects of azaspiracids 2 and 3 on intracellular cAMP, [Ca${}^{{2+}}$], and pH, Chem. Res. Toxicol. 17(10), 1338–1349 (2004)CrossRefGoogle Scholar
  233. [37.233]
    A. Furey, S. O'Doherty, K. O'Callaghan, M. Lehane, K.J. James: Azaspiracid poisoning (AZP) toxins in shellfish: Toxicological and health considerations, Toxicon 56(2), 173–190 (2010)CrossRefGoogle Scholar
  234. [37.234]
    G. Ronzitti, P. Hess, N. Rehmann, G.P. Rossini: Azaspiracid-1 alters the E-cadherin pool in epithelial cells, Toxicol. Sci. 95(2), 427–435 (2007)CrossRefGoogle Scholar
  235. [37.235]
    M.J. Twiner, P. Hess, M.Y. Dechraoui, T. McMahon, M.S. Samons, M. Satake, T. Yasumoto, J.S. Ramsdell, G.J. Doucette: Cytotoxic and cytoskeletal effects of azaspiracid-1 on mammalian cell lines, Toxicon 45(7), 891–900 (2005)CrossRefGoogle Scholar
  236. [37.236]
    N. Vilariño, K.C. Nicolaou, M.O. Frederick, E. Cagide, I.R. Ares, M.C. Louzao, M.R. Vieytes, L.M. Botana: Cell growth inhibition and actin cytoskeleton disorganization induced by azaspiracid-1 structure–activity studies, Chem. Res. Toxicol. 19(11), 1459–1466 (2006)CrossRefGoogle Scholar
  237. [37.237]
    M. Bellocci, G.L. Sala, F. Callegari, G.P. Rossini: Azaspiracid-1 inhibits endocytosis of plasma membrane proteins in epithelial cells, Toxicol. Sci. 117(1), 109–121 (2010)CrossRefGoogle Scholar
  238. [37.238]
    P. Hess, P. McCarron, N. Rehmann, J. Kilcoyne, T. McMahon, G. Ryan, M.P. Ryan, G.J. Doucette: Isolation and Purification of Azaspiracids from Naturally Contaminated Materials and Evaluation of Their Toxicological Effects. Final Project Report, Marine Enviromental and Health Series, Vol. 129 (Marine Institute, Galway, Ireland 2007)Google Scholar
  239. [37.239]
    E. Ito, M. Satake, K. Ofuji, M. Higashi, K. Harigaya, T. McMahon, T. Yasumoto: Chronic effects in mice caused by oral administration of sublethal doses of azaspiracid, a new marine toxin isolated from mussels, Toxicon 40(2), 193–203 (2002)CrossRefGoogle Scholar
  240. [37.240]
    M. Satake, K. Ofuji, H. Naoki, K.J. James, A. Furey, T. McMahon, J. Silke, T. Yasumoto: Azaspiracid, a new marine toxin having unique spiro ring assemblies, isolated from Irish mussels, Mytilus edulis, J. Am. Chem. Soc. 120(38), 9967–9968 (1998)CrossRefGoogle Scholar
  241. [37.241]
    K. Ofuji, M. Satake, T. McMahon, J. Silke, K.J. James, H. Naoki, Y. Oshima, T. Yasumoto: Two analogs of azaspiracid isolated from mussels, Mytilus edulis, involved in human intoxication in Ireland, Nat. Toxins 7(3), 99–102 (1999)CrossRefGoogle Scholar
  242. [37.242]
    E. Ito, K. Terao, T. McMahon, J. Silke, T. Yasumoto: Acute pathological changes in mice caused by crude extracts of novel toxins isolated from Irish mussels. In: Harmful Algae, ed. by B. Reguera, J. Blanco, M.L. Fernández, T. Wyatt (Intergovernmental Oceanographic Commission of UNESCO, Santiago de Compostela 1998) pp. 588–589Google Scholar
  243. [37.243]
    E. Ito, M. Satake, K. Ofuji, T. McMahone, J. Silke, K. James, T. Yasumoto: Small intestinal injuries in mice caused by and new toxing, azaspiracid, isolated from Irish mussels. In: Harmful and Toxic Algal Blooms, ed. by T. Yasumoto, Y. Oshima, Y. Fukuyo (Intergovernmental Oceanographic Commission of UNESCO, Santiago de Compostela 2000) p. 395Google Scholar
  244. [37.244]
    A.F. Flanagan, K.R. Callanan, J. Donlon, R. Palmer, A. Forde, M. Kane: A cytotoxicity assay for the detection and differentiation of two families of shellfish toxins, Toxicon 39(7), 1021–1027 (2001)CrossRefGoogle Scholar
  245. [37.245]
    Z. Cao, K.T. LePage, M.O. Frederick, K.C. Nicolaou, T.F. Murray: Involvement of caspase activation in azaspiracid-induced neurotoxicity in neocortical neurons, Toxicol. Sci. 114(2), 323–334 (2010)CrossRefGoogle Scholar
  246. [37.246]
    European Food Safety Authority: Marine biotoxins in shellfish-Saxitoxin group. Scientific opinion of the Panel on Contaminants in the Food Chain, EFSA Journal 1019, 1–76 (2009)Google Scholar
  247. [37.247]
    R. Shinohara, T. Akimoto, O. Iwamoto, T. Hirokawa, M. Yotsu-Yamashita, K. Yamaoka, K. Nagasawa: Synthesis of skeletal analogues of saxitoxin derivatives and evaluation of their inhibitory activity on sodium ion channels Na${}_{{\text{v}}}$1.4 and Na${}_{{\text{v}}}$1.5, Chem. Eur. J. 17(43), 12144–12152 (2011)CrossRefGoogle Scholar
  248. [37.248]
    S.A. Murray, M. Wiese, B.A. Neilan, R.J.S. Orr, M. de Salas, S. Brett, G. Hallegraeff: A reinvestigation of saxitoxin production and sxtA in the 'non-toxic' Alexandrium tamarense group V clade, Harmful Algae 18, 96–104 (2012)CrossRefGoogle Scholar
  249. [37.249]
    M.C. Wylie, V.M. Johnson, E. Carpino, K. Mullen, K. Hauser, A. Nedder, J.N. Kheir, A.J. Rodriguez-Navarro, D. Zurakowski, C.B. Berde: Respiratory, neuromuscular, and cardiovascular effects of neosaxitoxin in isoflurane-anesthetized sheep, Reg. Anesth. Pain Med. 37(2), 152–158 (2012)CrossRefGoogle Scholar
  250. [37.250]
    A.M.S. Mayer, M.T. Hamann: Marine pharmacology in 2001–2002: Marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action, Comp. Biochem. Physiol. C 140(3–4), 265–286 (2005)Google Scholar
  251. [37.251]
    I.A. Ross, W. Johnson, P.P. Sapienza, C.S. Kim: Effects of the seafood toxin domoic acid on glutamate uptake by rat astrocytes, Food Chem. Toxicol. 38(11), 1005–1011 (2000)CrossRefGoogle Scholar
  252. [37.252]
    G. Giordano, T.J. Kavanagh, E.M. Faustman, C.C. White, L.G. Costa: Low-level domoic acid protects mouse cerebellar granule neurons from acute neurotoxicity: Role of glutathione, Toxicol. Sci. 132(2), 399–408 (2013)CrossRefGoogle Scholar
  253. [37.253]
    M.A. Friedman, L.E. Fleming, M. Fernandez, P. Bienfang, K. Schrank, R. Dickey, M.-Y. Bottein, L. Backer, R. Ayyar, R. Weisman, S. Watkins, R. Granade, A. Reich: Ciguatera fish poisoning: Treatment, prevention and management, Mar. Drugs 6(3), 456–479 (2008)CrossRefGoogle Scholar
  254. [37.254]
    R.W. Dickey, S.M. Plakas: Ciguatera: A public health perspective, Toxicon 56(2), 123–136 (2010)CrossRefGoogle Scholar
  255. [37.255]
    G.M. Nicholson, R.J. Lewis: Ciguatoxins: Cyclic polyether modulators of voltage-gated Iion channel function, Mar. Drugs 4(3), 82–118 (2006)CrossRefGoogle Scholar
  256. [37.256]
    R.N. Murrell, J.E. Gibson: Brevetoxins 2, 3, 6, and 9 show variability in potency and cause significant induction of DNA damage and apoptosis in Jurkat E6-1 cells, Arch. Toxicol. 83(11), 1009–1019 (2009)CrossRefGoogle Scholar
  257. [37.257]
    N.V. Kulagina, T.J. O'Shaughnessy, W. Ma, J.S. Ramsdell, J.J. Pancrazio: Pharmacological effects of the marine toxins, brevetoxin and saxitoxin, on murine frontal cortex neuronal networks, Toxicon 44(6), 669–676 (2004)CrossRefGoogle Scholar
  258. [37.258]
    R.N. Murrell, J.E. Gibson: Brevetoxin 2 alters expression of apoptotic, DNA damage and cytokine genes in Jurkat cells, Hum. Exp. Toxicol. 30(3), 182–191 (2010)CrossRefGoogle Scholar
  259. [37.259]
    S.C. Hilderbrand, R.N. Murrell, J.E. Gibson, J.M. Brown: Marine brevetoxin induces IgE-independent mast cell activation, Arch. Toxicol. 85(2), 135–141 (2011)CrossRefGoogle Scholar
  260. [37.260]
    Z. Cao, J. George, W.H. Gerwick, D.G. Baden, J.D. Rainier, T.F. Murray: Influence of lipid-soluble gating modifier toxins on sodium influx in neocortical neurons, J. Pharmacol. Exp. Ther. 326(2), 604–613 (2008)CrossRefGoogle Scholar
  261. [37.261]
    P. Taupin: Brevetoxin derivative compounds for stimulating neuronal growth, Expert Opin. Ther. Pat. 19(2), 269–274 (2009)CrossRefGoogle Scholar
  262. [37.262]
    S. Bragadeeswaran, D. Therasa, K. Prabhu, K. Kathiresan: Biomedical and pharmacological potential of tetrodotoxin-producing bacteria isolated from marine pufferfish Arothron hispidus (Muller, 1841), J. Venom. Anim. Toxins Incl. Trop. Dis. 16(3), 421–431 (2011)CrossRefGoogle Scholar
  263. [37.263]
    B. Hegyi, I. Komaromi, K. Kistamas, F. Ruzsnavszky, K. Vaczi, B. Horvath, J. Magyar, T. Banyasz, P.P. Nanasi, N. Szentandrassy: Tetrodotoxin blockade on canine cardiac L-Type Ca${}^{{2+}}$ channels depends on pH and redox potential, Mar. Drugs 11(6), 2140–2153 (2013)CrossRefGoogle Scholar
  264. [37.264]
    F.R. Nieto, E.J. Cobos, M.A. Tejada, C. Sanchez-Fernandez, R. Gonzalez-Cano, C.M. Cendan: Tetrodotoxin (TTX) as a therapeutic agent for pain, Mar. Drugs 10(2), 281–305 (2012)CrossRefGoogle Scholar
  265. [37.265]
    A. Turabi, A.R. Plunkett: The application of genomic and molecular data in the treatment of chronic cancer pain, J. Surg. Oncol. 105(5), 494–501 (2012)CrossRefGoogle Scholar
  266. [37.266]
    F.R. Nieto, J.M. Entrena, C.M. Cendán, E. del Pozo, J.M. Vela, J.M. Baeyens: Tetrodotoxin inhibits the development and expression of neuropathic pain induced by paclitaxel in mice, Pain 137, 520–531 (2008)CrossRefGoogle Scholar
  267. [37.267]
    N.A. Hagen, P. du Souich, B. Lapointe, M. Ong-Lam, B. Dubuc, D. Walde, R. Love, A.H. Ngoc: Tetrodotoxin for moderate to severe cancer pain: A randomized, double blind, parallel design multicenter study, J. Pain Symptom Manag. 35(4), 420–429 (2008)CrossRefGoogle Scholar
  268. [37.268]
    N.A. Hagen, B. Lapointe, M. Ong-Lam, B. Dubuc, D. Walde, B. Gagnon, R. Love, R. Goel, P. Hawley, A.H. Ngoc, P. du Souich: A multicentre open-label safety and efficacy study of tetrodotoxin for cancer pain, Curr. Oncol. 18(3), E109–E116 (2011)CrossRefGoogle Scholar
  269. [37.269]
    F.R. Nieto, E.J. Cobos, M.Á. Tejada, C. Sánchez-Fernández, R. González-Cano, C. Miguel Cendán: Tetrodotoxin (TTX) as a therapeutic agent for pain, Mar. Drugs 10, 281–305 (2012)CrossRefGoogle Scholar
  270. [37.270]
    L. Wang, S.A. Shankarappa, R. Tong, J.B. Ciolino, J.H. Tsui, H.H. Chiang, D.S. Kohane: Topical drug formulations for prolonged corneal anesthesia, Cornea 32(7), 1040–1045 (2013)CrossRefGoogle Scholar
  271. [37.271]
    C. Vale: Palytoxins: Pharmacology and biological detection methods. In: Seafood and Freshwater Toxins: Pharmacology, Physiology and Detection, ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 675–691CrossRefGoogle Scholar
  272. [37.272]
    A. Tubaro, G. Del Favero, D. Beltramo, M. Ardizzone, M. Forino, M. De Bortoli, M. Pelin, M. Poli, G. Bignami, P. Ciminiello, S. Sosa: Acute oral toxicity in mice of a new palytoxin analog: 42-Hydroxy-palytoxin, Toxicon 57(5), 755–763 (2011)CrossRefGoogle Scholar
  273. [37.273]
    E.V. Wattenberg: Palytoxin: Exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis, Am. J. Physiol. Cell Physiol. 292(1), C24–C32 (2007)CrossRefGoogle Scholar
  274. [37.274]
    E.V. Wattenberg: Modulation of protein kinase signaling cascades by palytoxin, Toxicon 57(3), 440–448 (2011)CrossRefGoogle Scholar
  275. [37.275]
    R. Munday: Ocurrence and toxicology of palytoxins. In: Seafood and Freshwater Toxins: Pharmacology, Physiology and Detection, ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 693–713CrossRefGoogle Scholar
  276. [37.276]
    I. Valverde, J. Lago, A. Reboreda, J.M. Vieites, A.G. Cabado: Characteristics of palytoxin-induced cytotoxicity in neuroblastoma cells, Toxicol. In Vitro 22(6), 1432–1439 (2008)CrossRefGoogle Scholar
  277. [37.277]
    I. Valverde, J. Lago, J.M. Vieites, A.G. Cabado: In vitro approaches to evaluate palytoxin-induced toxicity and cell death in intestinal cells, J. Appl. Toxicol. 28(3), 294–302 (2008)CrossRefGoogle Scholar
  278. [37.278]
    M. Stewart, J.W. Blunt, M.H.G. Munro, W.T. Robinson, D.J. Hannah: The absolute stereochemistry of the New Zealand shellfish toxin gymnodimine, Tetrahedron Lett. 38, 4889–4890 (1997)CrossRefGoogle Scholar
  279. [37.279]
    R. Munday: Toxicology of cyclic imines: Gymnodimine, spirolides, pinnatoxins, pteriatoxins, prorocentrolide, spiro-prorocentrimine, and symbioimines. In: Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection, 2nd edn., ed. by L.M. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 581–594CrossRefGoogle Scholar
  280. [37.280]
    S.M. Gueret, M.A. Brimble: Spiroimine shellfish poisoning (SSP) and the spirolide family of shellfish toxins: Isolation, structure, biological activity and synthesis, Nat. Prod. Rep. 27(9), 1350–1366 (2010)CrossRefGoogle Scholar
  281. [37.281]
    R. Kharrat, D. Servent, E. Girard, G. Ouanounou, M. Amar, R. Marrouchi, E. Benoit, J. Molgó: The marine phycotoxin gymnodimine targets muscular and neuronal nicotinic acetylcholine receptor subtypes with high affinity, J. Neurochem. 107(4), 952–963 (2008)Google Scholar
  282. [37.282]
    Y. Bourne, Z. Radic, R. Aráoz, T.T. Talley, E. Benoit, D. Servent, P. Taylor, J. Molgó, P. Marchot: Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism, Proc. Natl. Acad. Sci. USA 107(13), 6076–6081 (2010)CrossRefGoogle Scholar
  283. [37.283]
    C.B. Wandscheer, N. Vilariño, B. Espiña, M.C. Louzao, L.M. Botana: Human muscarinic acetylcholine receptors are a target of the marine toxin 13-desmethyl C spirolide, Chem. Res. Toxicol. 23(11), 1753–1761 (2010)CrossRefGoogle Scholar
  284. [37.284]
    C.L. Trevino, L. Escobar, L. Vaca, V. Morales-Tlalpan, A.Y. Ocampo, A. Darszon: Maitotoxin; a unique pharmacological tool for elucidating Ca${}^{{2+}}$-dependent mechanisms. In: Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection, ed. by L. Botana (CRC/Taylor Francis, Boca Raton 2008) pp. 503–516Google Scholar
  285. [37.285]
    M.C. Louzao, E. Cagide, M.R. Vieytes, M. Sasaki, H. Fuwa, T. Yasumoto, L.M. Botana: The sodium channel of human excitable cells is a target for gambierol, Cell. Physiol. Biochem. 17(5/6), 257–268 (2006)CrossRefGoogle Scholar
  286. [37.286]
    E. Cagide, M.C. Louzao, B. Espina, I.R. Ares, M.R. Vieytes, M. Sasaki, H. Fuwa, C. Tsukano, Y. Konno, M. Yotsu-Yamashita, L.A. Paquette, T. Yasumoto, L.M. Botana: Comparative cytotoxicity of gambierol versus other marine neurotoxins, Chem. Res. Toxicol. 24(6), 835–842 (2011)CrossRefGoogle Scholar
  287. [37.287]
    E. Alonso, H. Fuwa, C. Vale, Y. Suga, T. Goto, Y. Konno, M. Sasaki, F.M. LaFerla, M.R. Vieytes, L. Gimenez-Llort, L.M. Botana: Design and synthesis of skeletal analogues of gambierol: Attenuation of amyloid-β and tau pathology with voltage-gated potassium channel and n-Methyl-d-aspartate receptor implications, J. Am. Chem. Soc. 134(17), 7467–7479 (2012)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Aníbal Martínez
    • 1
  • Alejandro Garrido-Maestu
    • 4
  • Begoña Ben-Gigirey
    • 2
  • María José Chapela
    • 3
  • Virginia González
    • 1
  • Juan M. Vieites
    • 5
  • Ana G. Cabado
    • 1
  1. 1.Food Quality and SafetyANFACO-CECOPESCAVigo-PoSpain
  2. 2.EU Reference Laboratory for Marine BiotoxinsMinistry of HealthVigoSpain
  3. 3.Research & DevelopmentANFACO-CECOPESCAVigo-PoSpain
  4. 4.Microbiology and Bioassays LaboratoryANFACO-CECOPESCAVigo-PoSpain
  5. 5.General ManagementANFACO-CECOPESCAVigo-PoSpain

Personalised recommendations