Advertisement
Review Article| Volume 26, ISSUE 2, P397-419, June 2006

Toxins: Bacterial and Marine Toxins

      The term toxin refers in a specific way to a toxic substance of biologic origin; that is, a true toxin is a poison produced by a living organism. The more generic term, inclusive of both the naturally occurring toxins and of harmful substances produced in a laboratory or by other synthetic means, is toxicants [
      • Madsen J.
      Toxins as weapons of mass destruction. A comparison and contrast with biological warfare and chemical warfare agents.
      ]. The purpose of this article is to review some of the most potentially dangerous toxins of concern today. Mechanisms of action, routes of exposure, diagnostic tools, and treatment recommendations are addressed. In addition, current therapeutic uses for certain toxins are discussed.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Madsen J.
        Toxins as weapons of mass destruction. A comparison and contrast with biological warfare and chemical warfare agents.
        Clin Lab Med. 2001; 21: 593-605
      1. Shapiro DS WA. Sentinel laboratory guidelines for suspected agents of bioterrorism. Botulinum. Available at: http://www.asm.org/ASM/files/LEFTMARGINHEADERLIST/downloadfilename/0000000522/BotulismFinalVersion73003.pdf. Accessed January 6, 2006.

        • Centers for Disease Control and Prevention
        Botulism in the United States, 1899–1996. Handbook for epidemiologists, clinicians and laboratory workers.
        Centers for Disease Control and Prevention, Atlanta (GA)1998
        • Aktories K.
        • Barth H.
        Clostridium botulinum C2 toxin—new insights into the cellular up-take of the actin-ADP-ribosylating toxin.
        Int J Med Microbiol. 2004; 293: 557-564
        • Caya J.G.
        • Agni R.
        • Miller J.E.
        Clostridium botulinum and the clinical laboratorian: a detailed review of botulism, including biological warfare ramifications of botulinum toxin.
        Arch Pathol Lab Med. 2004; 128: 653-662
        • Barash J.R.
        • Tang T.W.
        • Arnon S.S.
        First case of infant botulism caused by Clostridium baratii type F in California.
        J Clin Microbiol. 2005; 43: 4280-4282
        • Centers for Disease Control and Prevention
        Botulism outbreak associated with eating fermented foods—Alaska, 2001.
        MMWR Morb Mortal Wkly Rep. 2001; 50: 680-682
        • Liu W.
        • Montana V.
        • Chapman E.R.
        • et al.
        Botulinum toxin type B micromechanosensor.
        Proc Natl Acad Sci USA. 2003; 100: 13621-13625
        • Parpura V.
        • Chapman E.R.
        Detection of botulinum toxins: micromechanical and fluorescence-based sensors.
        Croat Med J. 2005; 46: 491-497
        • Centers for Disease Control and Prevention
        Wound botulism—California, 1995.
        MMWR Morb Mortal Wkly Rep. 1995; 44: 889-892
        • Goetz C.G.
        • Meisel E.
        Selected classic examples of neurotoxic disorders—biological neurotoxins.
        Neurol Clin. 2000; 18: 719-740
        • Marks J.D.
        Medical aspects of biologic toxins.
        Anesthesiol Clin North America. 2004; 22 (vii): 509-532
      2. Bioterriorism Agents/Diseases by Category. Available at: http://www.bt.cdc.gov/agent/agentlist-category.asp. Accessed January 3, 2006.

      3. Darling RG WJ. USAMRIID's medical management of biological casualties handbook. 5th edition. Frederick (MD): US Army Medical Research Institute; 2004.

        • Ahn-Yoon S.
        • DeCory T.R.
        • Durst R.A.
        Ganglioside-liposome immunoassay for the detection of botulinum toxin.
        Anal Bioanal Chem. 2004; 378: 68-75
        • Arnon S.S.
        • Schechter R.
        • Inglesby T.V.
        • et al.
        Botulinum toxin as a biological weapon: medical and public health management.
        JAMA. 2001; 285: 1059-1070
        • Schiavo G.
        • Benfenati F.
        • Poulain B.
        • et al.
        Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin.
        Nature. 1992; 359: 832-835
        • Schiavo G.
        • Shone C.C.
        • Rossetto O.
        • et al.
        Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin.
        J Biol Chem. 1993; 268: 11516-11519
        • Dressler D.
        • Saberi F.A.
        • Barbosa E.R.
        Botulinum toxin: mechanisms of action.
        Eur Neurol. 2005; 63: 180-185
        • Montecucco C.
        • Molgo J.
        Botulinal neurotoxins: revival of an old killer.
        Curr Opin Pharmacol. 2005; 5: 274-279
        • Moorthy J.
        • Mensing G.A.
        • Kim D.
        • et al.
        Microfluidic tectonics platform: a colorimetric, disposable botulinum toxin enzyme–linked immunosorbent assay system.
        Electrophoresis. 2004; 25: 1705-1713
        • Chiao D.J.
        • Shyu R.H.
        • Hu C.S.
        • et al.
        Colloidal gold-based immunochromatographic assay for detection of botulinum neurotoxin type B.
        J Chromatogr B Analyt Technol Biomed Life Sci. 2004; 809: 37-41
        • Barr J.R.
        • Moura H.
        • Boyer A.E.
        • et al.
        Botulinum neurotoxin detection and differentiation by mass spectrometry.
        Emerg Infect Dis. 2005; 11: 1578-1583
      4. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. The Pink Book. 8th edition. Available at: http://www.cdc.gov/nip/publications/pink. Accessed January 4, 2006.

        • Montecucco C.
        • Schiavo G.
        Mechanism of action of tetanus and botulinum neurotoxins.
        Mol Microbiol. 1994; 13: 1-8
        • Goonetilleke A.
        • Harris J.B.
        Clostridial neurotoxins.
        J Neurol Neurosurg Psychiatry. 2004; 75: iii35-iii39
      5. Pascual FB ME, Zanardi LR, Cortese MM, et al. Tetanus surveillance—United States 1998–2000. MMWR CDC Surveill Summ 2003;52(SS03):1–8.

        • Thwaites C.L.
        • Farrar J.J.
        Preventing and treating tetanus.
        BMJ. 2003; 326: 117-118
        • Akbulut D.
        • Grant K.A.
        • McLauchlin J.
        Improvement in laboratory diagnosis of wound botulism and tetanus among injecting illicit-drug users by use of real-time PCR assays for neurotoxin gene fragments.
        J Clin Microbiol. 2005; 43: 4342-4348
        • Shoop W.L.
        • Xiong Y.
        • Wiltsie J.
        • et al.
        Anthrax lethal factor inhibition.
        Proc Natl Acad Sci USA. 2005; 102: 7958-7963
        • Collier R.J.
        • Young J.A.
        Anthrax toxin.
        Annu Rev Cell Dev Biol. 2003; 19: 45-70
        • Brossier F.
        • Mock M.
        Toxins of Bacillus anthracis.
        Toxicon. 2001; 39: 1747-1755
        • Petosa C.
        • Collier R.J.
        • Klimpel K.R.
        • et al.
        Crystal structure of the anthrax toxin protective antigen.
        Nature. 1997; 385: 833-838
        • Gordon V.M.
        • Klimpel K.R.
        • Arora N.
        • et al.
        Proteolytic activation of bacterial toxins by eukaryotic cells is performed by furin and by additional cellular proteases.
        Infect Immun. 1995; 63: 82-87
        • Leppla S.H.
        Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
        Proc Natl Acad Sci USA. 1982; 79: 3162-3166
        • Tournier J.N.
        • Quesnel-Hellmann A.
        • Mathieu J.
        • et al.
        Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells.
        J Immunol. 2005; 174: 4934-4941
        • Paccani S.R.
        • Tonello F.
        • Ghittoni R.
        • et al.
        Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling.
        J Exp Med. 2005; 201: 325-331
        • Klimpel K.R.
        • Arora N.
        • Leppla S.H.
        Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity.
        Mol Microbiol. 1994; 13: 1093-1100
        • Duesbery N.S.
        • Webb C.P.
        • Leppla S.H.
        • et al.
        Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor.
        Science. 1998; 280: 734-737
        • Park J.M.
        • Greten F.R.
        • Li Z.W.
        • et al.
        Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition.
        Science. 2002; 297: 2048-2051
        • Kirby J.E.
        Anthrax lethal toxin induces human endothelial cell apoptosis.
        Infect Immun. 2004; 72: 430-439
      6. Questions and answer about anthrax. Available at: http://www.bt.cdc.gov/agent/anthrax/faq. Accessed December 10, 2005.

        • Inglesby T.V.
        • O'Toole T.
        • Henderson D.A.
        • et al.
        Anthrax as a biological weapon, 2002: updated recommendations for management.
        JAMA. 2002; 287: 2236-2252
      7. Approved tests for the detection of Bacillus anthracis in the laboratory response network. Available at: http://www.bt.cdc.gov/agent/anthrax/lab-testing/approvedlrntests.asp. Accessed January 3, 2006.

        • Centers for Disease Control and Prevention
        Update: investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001.
        MMWR Morb Mortal Wkly Rep. 2001; 50: 909-919
        • Dalsgaard A.
        • Serichantalergs O.
        • Forslund A.
        • et al.
        Clinical and environmental isolates of Vibrio cholerae serogroup O141 carry the CTX phage and the genes encoding the toxin-coregulated pili.
        J Clin Microbiol. 2001; 39: 4086-4092
        • Sixma T.K.
        • Kalk K.H.
        • van Zanten B.A.
        • et al.
        Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin.
        J Mol Biol. 1993; 230: 890-918
        • Zhang R.G.
        • Scott D.L.
        • Westbrook M.L.
        • et al.
        The three-dimensional crystal structure of cholera toxin.
        J Mol Biol. 1995; 251: 563-573
        • Holmgren J.
        • Lonnroth I.
        • Mansson J.
        • et al.
        Interaction of cholera toxin and membrane GM1 ganglioside of small intestine.
        Proc Natl Acad Sci USA. 1975; 72: 2520-2524
        • Fujinaga Y.
        • Wolf A.A.
        • Rodighiero C.
        • et al.
        Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulum.
        Mol Biol Cell. 2003; 14: 4783-4793
        • Lencer W.I.
        Retrograde transport of cholera toxin into the ER of host cells.
        Int J Med Microbiol. 2004; 293: 491-494
        • Cassel D.
        • Selinger Z.
        Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site.
        Proc Natl Acad Sci USA. 1977; 74: 3307-3311
        • Rodighiero C.
        • Aman A.T.
        • Kenny M.J.
        • et al.
        Structural basis for the differential toxicity of cholera toxin and Escherichia coli heat-labile enterotoxin. Construction of hybrid toxins identifies the A2-domain as the determinant of differential toxicity.
        J Biol Chem. 1999; 274: 3962-3969
        • Lu L.
        • Baldeon M.E.
        • Savidge T.
        • et al.
        Development of microbial–human enterocyte interaction: cholera toxin.
        Pediatr Res. 2003; 54: 212-218
      8. Bopp CA RA, Wells JG. Laboratory methods for the diagnosis of epidemic dysentery and cholera. Atlanta (GA): Centers for Disease Control and Prevention; 1999.

        • Centers for Disease Control and Prevention
        Current trends update: cholera—Western Hemisphere, and recommendations for treatment of cholera.
        MMWR Morb Mortal Wkly Rep. 1991; 40: 562-565
      9. Centers for Disease Control and Prevention. Update on cholera vaccine. Available at: http://www.cdc.gov/travel/other/cholera-vaccine.htm. Accessed January 4, 2006.

        • Karch H.
        The role of virulence factors in enterohemorrhagic Escherichia coli (EHEC)–associated hemolytic-uremic syndrome.
        Semin Thromb Hemost. 2001; 27: 207-213
        • Watanabe M.
        • Matsuoka K.
        • Kita E.
        • et al.
        Oral therapeutic agents with highly clustered globotriose for treatment of Shiga toxigenic Escherichia coli infections.
        J Infect Dis. 2004; 189: 360-368
        • Obrig T.G.
        • Louise C.B.
        • Lingwood C.A.
        • et al.
        Endothelial heterogeneity in Shiga toxin receptors and responses.
        J Biol Chem. 1993; 268: 15484-15488
        • Sherman P.
        • Soni R.
        • Karmali M.
        Attaching and effacing adherence of Vero cytotoxin–producing Escherichia coli to rabbit intestinal epithelium in vivo.
        Infect Immun. 1988; 56: 756-761
        • Cherla R.P.
        • Lee S.Y.
        • Tesh V.L.
        Shiga toxins and apoptosis.
        FEMS Microbiol Lett. 2003; 228: 159-166
        • Endo Y.
        • Tsurugi K.
        • Yutsudo T.
        • et al.
        Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the toxins.
        Eur J Biochem. 1988; 171: 45-50
        • Obrig T.G.
        • Moran T.P.
        • Brown J.E.
        The mode of action of Shiga toxin on peptide elongation of eukaryotic protein synthesis.
        Biochem J. 1987; 244: 287-294
        • Yoshida T.
        • Koide N.
        • Sugiyama T.
        • et al.
        A novel caspase dependent pathway is involved in apoptosis of human endothelial cells by Shiga toxins.
        Microbiol Immunol. 2002; 46: 697-700
        • Colpoys W.E.
        • Cochran B.H.
        • Carducci T.M.
        • et al.
        Shiga toxins activate translational regulation pathways in intestinal epithelial cells.
        Cell Signal. 2005; 17: 891-899
        • Thorpe C.M.
        Shiga toxin–producing Escherichia coli infection.
        Clin Infect Dis. 2004; 38: 1298-1303
        • Centers for Disease Control and Prevention
        Escherichia coli O157:H7 outbreak linked to home-cooked hamburger—California, July 1993.
        MMWR Morb Mortal Wkly Rep. 1994; 43: 213-216
        • Siegler R.
        Central nervous system involvement in the hemolytic uremic syndrome.
        in: Kaplan B.S. Trompeter R.S. Moake J.L. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Marcel Dekker, New York1992
        • Wong C.S.
        • Jelacic S.
        • Habeeb R.L.
        • et al.
        The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections.
        N Engl J Med. 2000; 342: 1930-1936
        • Kimmitt P.T.
        • Harwood C.R.
        • Barer M.R.
        Toxin gene expression by shiga toxin–producing Escherichia coli: the role of antibiotics and the bacterial SOS response.
        Emerg Infect Dis. 2000; 6: 458-465
        • Centers for Disease Control and Prevention
        University outbreak of calicivirus infection mistakenly attributed to shiga toxin–producing Escherichia coli O157:H7—Virginia, 2000.
        MMWR Morb Mortal Wkly Rep. 2001; 50: 489-491
      10. Braden CLJ, Boothe E, Vugia D, et al. Testing to identify shiga toxin–producing E. coli in HUS patients: FoodNet 1997–2001. Presented at the International Conference on Emerging Infectious Diseases. Atlanta (GA), March 2002.

        • Isbister G.K.
        • Kiernan M.C.
        Neurotoxic marine poisoning.
        Lancet Neurol. 2005; 4: 219-228
        • Lange W.R.
        • Lipkin K.M.
        • Yang G.C.
        Can ciguatera be a sexually transmitted disease?.
        J Toxicol Clin Toxicol. 1989; 27: 193-197
        • Lehane L.
        Ciguatera fish poisoning: a review in a risk-assessment framework.
        National Office of Animal and Plant Health, Agriculture, Fisheries and Forestry, Canberra (Australia)1999
        • Mattei C.
        • Molgo J.
        • Marquais M.
        • et al.
        Hyperosmolar D-mannitol reverses the increased membrane excitability and the nodal swelling caused by Caribbean ciguatoxin-1 in single frog myelinated axons.
        Brain Res. 1999; 847: 50-58
        • Lehane L.
        • Lewis R.J.
        Ciguatera: recent advances but the risk remains.
        Int J Food Microbiol. 2000; 61: 91-125
      11. International Programme on Chemical Safety. Environmental health criteria 37. Aquatic (marine and freshwater) biotoxins. Available at: http://www.inchem.org/documents/ehc/ehc/ehc37.htm. Accessed January 4, 2006.

        • Centers for Disease Control and Prevention
        Ciguatera fish poisoning—Texas, 1997.
        MMWR Morb Mortal Wkly Rep. 1998; 43: 692-694
        • Lewis R.J.
        The changing face of ciguatera.
        Toxicon. 2001; 39: 97-106
      12. Oliver L. Recommendations for use of the Cigua-check test kit. Presented at the Fourth Workshop of the Australian Research Network for Algal Toxins (ARNAT). Townsville, Queensland, Australia. The Australian Institute of Marine Science, July 14, 2002.

        • Matta J.
        • Navas J.
        • Milad M.
        • et al.
        A pilot study for the detection of acute ciguatera intoxication in human blood.
        J Toxicol Clin Toxicol. 2002; 40: 49-57
        • Palafox N.A.
        • Jain L.G.
        • Pinano A.Z.
        • et al.
        Successful treatment of ciguatera fish poisoning with intravenous mannitol.
        JAMA. 1988; 259: 2740-2742
        • Schnorf H.
        • Taurarii M.
        • Cundy T.
        Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy.
        Neurology. 2002; 58: 873-880
        • Jeffery B.
        • Barlow T.
        • Moizer K.
        • et al.
        Amnesic shellfish poison.
        Food Chem Toxicol. 2004; 42: 545-557
        • Brown J.A.
        • Nijjar M.S.
        The release of glutamate and aspartate from rat brain synaptosomes in response to domoic acid (amnesic shellfish toxin) and kainic acid.
        Mol Cell Biochem. 1995; 151: 49-54
        • Stewart G.R.
        • Zorumski C.F.
        • Price M.T.
        • et al.
        Domoic acid: a dementia-inducing excitotoxic food poison with kainic acid receptor specificity.
        Exp Neurol. 1990; 110: 127-138
      13. Ravn H YT, Ramsdell T. Amnestic shellfish poisoning (ASP). Intergovernmental Oceanographic Commission HAB publication series 1995;1(31).

        • Peng Y.G.
        • Taylor T.B.
        • Finch R.E.
        • et al.
        Neuroexcitatory and neurotoxic actions of the amnesic shellfish poison, domoic acid.
        Neuroreport. 1994; 5: 981-985
        • Kizer K.W.
        Domoic acid poisoning.
        West J Med. 1994; 161: 59-60
        • Kawatsu K.
        • Hamano Y.
        • Noguchi T.
        Production and characterization of a monoclonal antibody against domoic acid and its application to enzyme immunoassay.
        Toxicon. 1999; 37: 1579-1589
        • Perl T.M.
        • Bedard L.
        • Kosatsky T.
        • et al.
        An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid.
        N Engl J Med. 1990; 322: 1775-1780
        • Teitelbaum J.S.
        • Zatorre R.J.
        • Carpenter S.
        • et al.
        Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels.
        N Engl J Med. 1990; 322: 1781-1787
        • Cendes F.
        • Andermann F.
        • Carpenter S.
        • et al.
        Temporal lobe epilepsy caused by domoic acid intoxication: evidence for glutamate receptor–mediated excitotoxicity in humans.
        Ann Neurol. 1995; 37: 123-126
        • Smith D.S.
        • Kitts D.D.
        A competitive enzyme-linked immunoassay for domoic acid determination in human body fluids.
        Food Chem Toxicol. 1994; 32: 1147-1154
      14. International Programme on Chemical Safety. Poisons information monograph 67. Available at: http://www.inchem.org/documents/pims/chemical/pim670.htm. Accessed January 4, 2006.

        • Pinsky C.
        • Glavin G.B.
        • Bose R.
        Kynurenic acid protects against neurotoxicity and lethality of toxic extracts from contaminated Atlantic coast mussels.
        Prog Neuropsychopharmacol Biol Psychiatry. 1989; 13: 595-598
        • Naar J.
        • Bourdelais A.
        • Tomas C.
        • et al.
        A competitive ELISA to detect brevetoxins from Karenia brevis (formerly Gymnodinium breve) in seawater, shellfish, and mammalian body fluid.
        Environ Health Perspect. 2002; 110: 179-185
        • Cheng Y.S.
        • McDonald J.D.
        • Kracko D.
        • et al.
        Concentration and particle size of airborne toxic algae (brevetoxin) derived from ocean red tide events.
        Environ Sci Technol. 2005; 39: 3443-3449
        • Baden D.G.
        • Bourdelais A.J.
        • Jacocks H.
        • et al.
        Natural and derivative brevetoxins: historical background, multiplicity, and effects.
        Environ Health Perspect. 2005; 113: 621-625
        • Bottein Dechraoui M.Y.
        • Ramsdell J.S.
        Type B brevetoxins show tissue selectivity for voltage-gated sodium channels: comparison of brain, skeletal muscle and cardiac sodium channels.
        Toxicon. 2003; 41: 919-927
        • Poli M.A.
        • Mende T.J.
        • Baden D.G.
        Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes.
        Mol Pharmacol. 1986; 30: 129-135
        • Baden D.G.
        Brevetoxins: unique polyether dinoflagellate toxins.
        FASEB J. 1989; 3: 1807-1817
        • Baden D.G.
        • Mende T.J.
        Toxicity of two toxins from the Florida red tide marine dinoflagellate, Ptychodiscus brevis.
        Toxicon. 1982; 20: 457-461
        • Baden D.G.
        • Mende T.J.
        • Bikhazi G.
        • et al.
        Bronchoconstriction caused by Florida red tide toxins.
        Toxicon. 1982; 20: 929-932
        • Woofter R.
        • Dechraoui M.Y.
        • Garthwaite I.
        • et al.
        Measurement of brevetoxin levels by radioimmunoassay of blood collection cards after acute, long-term, and low-dose exposure in mice.
        Environ Health Perspect. 2003; 111: 1595-1600
        • Trainer V.L.
        • Baden D.G.
        An enzyme immunoassay for the detection of Florida red tide brevetoxins.
        Toxicon. 1991; 29: 1387-1394
        • Poli M.A.
        • Musser S.M.
        • Dickey R.W.
        • et al.
        Neurotoxic shellfish poisoning and brevetoxin metabolites: a case study from Florida.
        Toxicon. 2000; 38: 981-993
      15. Australia New Zealand Food Authority. Shellfish toxins in food. A toxicological review and risk assessment. Technical report series number 14. p. 13–5. Available at: http://www.anzfa.gov. Accessed January 3, 2005.

        • Sorokin M.
        Puffer fish poisoning.
        Med J Aust. 1973; 1: 957
        • Ahasan H.A.
        • Mamun A.A.
        • Karim S.R.
        • et al.
        Paralytic complications of puffer fish (tetrodotoxin) poisoning.
        Singapore Med J. 2004; 45: 73-74
      16. Tetrodotoxin. Available at: http://www.pufferfish.co.uk/aquaria.species/general/tetro.htm. Accessed January 3, 2005.

        • Simidu U.
        • Noguchi T.
        • Hwang D.F.
        • et al.
        Marine bacteria which produce tetrodotoxin.
        Appl Environ Microbiol. 1987; 53: 1714-1715
        • Yu C.F.
        • Yu P.H.
        • Chan P.L.
        • et al.
        Two novel species of tetrodotoxin-producing bacteria isolated from toxic marine puffer fishes.
        Toxicon. 2004; 44: 641-647
      17. Tetrodotoxin: essentail data. Available at: http://www.cbwinfo.com/Biological/Toxins/TTX.html. Accessed January 3, 2006.

        • Cestele S.
        • Catterall W.A.
        Molecular mechanisms of neurotoxin action on voltage-gated sodium channels.
        Biochimie. 2000; 82: 883-892
        • Kiernan M.C.
        • Isbister G.K.
        • Lin C.S.
        • et al.
        Acute tetrodotoxin-induced neurotoxicity after ingestion of puffer fish.
        Ann Neurol. 2005; 57: 339-348
        • Lan M.Y.
        • Lai S.L.
        • Chen S.S.
        • et al.
        Tetrodotoxin intoxication in a uraemic patient.
        J Neurol Neurosurg Psychiatry. 1999; 67: 127-128
      18. Toxnet. Available at: http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/∼DPklSV:1. Accessed January 5, 2006.

        • How C.K.
        • Chern C.H.
        • Huang Y.C.
        • et al.
        Tetrodotoxin poisoning.
        Am J Emerg Med. 2003; 21: 51-54
        • O'Leary M.A.
        • Schneider J.J.
        • Isbister G.K.
        Use of high performance liquid chromatography to measure tetrodotoxin in serum and urine of poisoned patients.
        Toxicon. 2004; 44: 549-553
      19. Saxitoxins. Available at: http://www.aims.gov.au/arnat/arnat-0008.htm. Accessed January 9, 2006.

        • Okumura M.
        • Tsuzuki H.
        • Tomita B.
        A rapid detection method for paralytic shellfish poisoning toxins by cell bioassay.
        Toxicon. 2005; 46: 93-98
        • Dell'Aversano C.
        • Hess P.
        • Quilliam M.A.
        Hydrophilic interaction liquid chromatography—mass spectrometry for the analysis of paralytic shellfish poisoning (PSP) toxins.
        J Chromatogr A. 2005; 1081: 190-201
        • Garrido R.
        • Lagos N.
        • Lattes K.
        • et al.
        Gonyautoxin: new treatment for healing acute and chronic anal fissures.
        Dis Colon Rectum. 2005; 48: 335-340
        • Su Z.
        • Sheets M.
        • Ishida H.
        • et al.
        Saxitoxin blocks L-type ICa.
        J Pharmacol Exp Ther. 2004; 308: 324-329
        • Wang J.
        • Salata J.J.
        • Bennett P.B.
        Saxitoxin is a gating modifier of HERG K+ channels.
        J Gen Physiol. 2003; 121: 583-598
      20. Flemming LE. Paralytic shellfish poisoning. Available at: http://www.whoi.edu/redtide/illness/psp.html. Accessed January 10, 2006.

      21. Saxitoxin. In: Robinson J, editor. Public health response to biological and chemical weapons. WHO guidance. 2nd edition. Geneva (Switzerland): World Health Organization.

        • Lehane L.
        Paralytic shellfish poisoning: a review.
        National Office of Animal and Plant Health, Agriculture, Fisheries, and Forestry, Canberra (Australia)2000
        • Gessner B.D.
        • Bell P.
        • Doucette G.J.
        • et al.
        Hypertension and identification of toxin in human urine and serum following a cluster of mussel-associated paralytic shellfish poisoning outbreaks.
        Toxicon. 1997; 35: 711-722
      22. Vangelova L. Botulinum toxin: a poison that can heal. 1998. Available at: www.fda.gov/fdac/features/095_bot.html. Accessed January 3, 2006.

        • Frankel A.E.
        • Powell B.L.
        • Duesbery N.S.
        • et al.
        Anthrax fusion protein therapy of cancer.
        Curr Protein Pept Sci. 2002; 3: 399-407
        • Lavelle E.C.
        • Jarnicki A.
        • McNeela E.
        • et al.
        Effects of cholera toxin on innate and adaptive immunity and its application as an immunomodulatory agent.
        J Leukoc Biol. 2004; 75: 756-763
        • Nashar T.O.
        • Hirst T.R.
        • Williams N.A.
        Modulation of B-cell activation by the B subunit of Escherichia coli enterotoxin: receptor interaction up-regulates MHC class II, B7, CD40, CD25 and ICAM-1.
        Immunology. 1997; 91: 572-578