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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (28 February 2008)

Special Issue Editor

Guest Editor
Prof. Dr. Alejandro M. Mayer

Professor of Pharmacology, Department of Pharmacology, CCOM, Midwestern University, 555 31st. Street, Downers Grove, Illinois 60515, USA
Website | E-Mail
Fax: +1 630 515 6295
Interests: immunopharmacology, inflammation, leukocytes, cytokines, chemokines, superoxide, eicosanoids, marine toxins

Special Issue Information

Marine

Printed Edition Availble

A printed edition of this special issue is available in two volumes:

  • Volume A (ISBN 3-906980-21-9) - Review Articles, 390 p.; and
  • Volume B (ISBN 3-906980-22-7) - Research Articles, 172 p.

Price: 189 CHF (for both volumes, excl. shipping)
(Special price for contributing authors: 129 CHF)

To order a copy of the printed edition, send an e-mail to marinedrugs@mdpi.com. Pages containing colored figures are printed in color. A leaflet including the preface is available from following website.

Published Papers (25 papers)

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Editorial

Jump to: Research, Review

Open AccessEditorial Special Issue on Marine Toxins
Mar. Drugs 2009, 7(1), 19-23; doi:10.3390/md7010019
Received: 28 January 2009 / Published: 29 January 2009
Cited by 2 | PDF Full-text (94 KB) | HTML Full-text | XML Full-text
Abstract
The special issue on Marine Toxins of the Open Access journal Marine Drugs (ISSN 1660-3397, http://www.mdpi.com/journal/marinedrugs/) presents twenty four contributions which were received from distinguished investigators currently working in Canada, China, France, Germany, Iran, Italy, Japan, Portugal, Russian Federation, Slovenia, South Africa, Spain,
[...] Read more.
The special issue on Marine Toxins of the Open Access journal Marine Drugs (ISSN 1660-3397, http://www.mdpi.com/journal/marinedrugs/) presents twenty four contributions which were received from distinguished investigators currently working in Canada, China, France, Germany, Iran, Italy, Japan, Portugal, Russian Federation, Slovenia, South Africa, Spain, and the United States. The reviews and research articles provide the interested reader with a global view of marine toxins research during 2007-2008. [...] Full article
(This article belongs to the Special Issue Marine Toxins)

Research

Jump to: Editorial, Review

Open AccessArticle Recreational Exposure to Low Concentrations of Microcystins During an Algal Bloom in a Small Lake
Mar. Drugs 2008, 6(2), 389-406; doi:10.3390/md6020389
Received: 6 February 2008 / Revised: 5 June 2008 / Accepted: 19 June 2008 / Published: 26 June 2008
Cited by 42 | PDF Full-text (327 KB) | HTML Full-text | XML Full-text
Abstract
We measured microcystins in blood from people at risk for swallowing water or inhaling spray while swimming, water skiing, jet skiing, or boating during an algal bloom. We monitored water samples from a small lake as a Microcystis aeruginosa bloom developed. We recruited
[...] Read more.
We measured microcystins in blood from people at risk for swallowing water or inhaling spray while swimming, water skiing, jet skiing, or boating during an algal bloom. We monitored water samples from a small lake as a Microcystis aeruginosa bloom developed. We recruited 97 people planning recreational activities in that lake and seven others who volunteered to recreate in a nearby bloom-free lake. We conducted our field study within a week of finding a 10-μg/L microcystin concentration. We analyzed water, air, and human blood samples for water quality, potential human pathogens, algal taxonomy, and microcystin concentrations. We interviewed study participants for demographic and current health symptom information. Water samples were assayed for potential respiratory viruses (adenoviruses and enteroviruses), but none were detected. We did find low concentrations of Escherichia coli, indicating fecal contamination. We found low levels of microcystins (2 μg/L to 5 μg/L) in the water and (<0.1 ng/m3) in the aerosol samples. Blood levels of microcystins for all participants were below the limit of detection (0.147μg/L). Given this low exposure level, study participants reported no symptom increases following recreational exposure to microcystins. This is the first study to report that water-based recreational activities can expose people to very low concentrations of aerosol-borne microcystins; we recently conducted another field study to assess exposures to higher concentrations of these algal toxins. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Effects of in vitro Brevetoxin Exposure on Apoptosis and Cellular Metabolism in a Leukemic T Cell Line (Jurkat)
Mar. Drugs 2008, 6(2), 291-307; doi:10.3390/md6020291
Received: 3 January 2008 / Revised: 7 May 2008 / Accepted: 4 June 2008 / Published: 10 June 2008
Cited by 17 | PDF Full-text (294 KB) | HTML Full-text | XML Full-text
Abstract
Harmful algal blooms (HABs) of the toxic dinoflagellate, Karenia brevis, produce red tide toxins, or brevetoxins. Significant health effects associated with red tide toxin exposure have been reported in sea life and in humans, with brevetoxins documented within immune cells from many species.
[...] Read more.
Harmful algal blooms (HABs) of the toxic dinoflagellate, Karenia brevis, produce red tide toxins, or brevetoxins. Significant health effects associated with red tide toxin exposure have been reported in sea life and in humans, with brevetoxins documented within immune cells from many species. The objective of this research was to investigate potential immunotoxic effects of brevetoxins using a leukemic T cell line (Jurkat) as an in vitro model system. Viability, cell proliferation, and apoptosis assays were conducted using brevetoxin congeners PbTx-2, PbTx-3, and PbTx-6. The effects of in vitro brevetoxin exposure on cell viability and cellular metabolism or proliferation were determined using trypan blue and MTT (1-(4,5-dimethylthiazol-2-yl)-3,5- diphenylformazan), respectively. Using MTT, cellular metabolic activity was decreased in Jurkat cells exposed to 5 - 10 μg/ml PbTx-2 or PbTx-6. After 3 h, no significant effects on cell viability were observed with any toxin congener in concentrations up to 10 μg/ml. Viability decreased dramatically after 24 h in cells treated with PbTx-2 or -6. Apoptosis, as measured by caspase-3 activity, was significantly increased in cells exposed to PbTx-2 or PbTx-6. In summary, brevetoxin congeners varied in effects on Jurkat cells, with PbTx-2 and PbTx-6 eliciting greater cellular effects compared to PbTx-3. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Diverse Bacterial PKS Sequences Derived From Okadaic Acid-Producing Dinoflagellates
Mar. Drugs 2008, 6(2), 164-179; doi:10.3390/md6020164
Received: 29 February 2008 / Revised: 9 May 2008 / Accepted: 13 May 2008 / Published: 22 May 2008
Cited by 13 | PDF Full-text (1139 KB) | HTML Full-text | XML Full-text
Abstract
Okadaic acid (OA) and the related dinophysistoxins are isolated from dinoflagellates of the genus Prorocentrum and Dinophysis. Bacteria of the Roseobacter group have been associated with okadaic acid producing dinoflagellates and have been previously implicated in OA production. Analysis of 16S rRNA
[...] Read more.
Okadaic acid (OA) and the related dinophysistoxins are isolated from dinoflagellates of the genus Prorocentrum and Dinophysis. Bacteria of the Roseobacter group have been associated with okadaic acid producing dinoflagellates and have been previously implicated in OA production. Analysis of 16S rRNA libraries reveals that Roseobacter are the most abundant bacteria associated with OA producing dinoflagellates of the genus Prorocentrum and are not found in association with non-toxic dinoflagellates. While some polyketide synthase (PKS) genes form a highly supported Prorocentrum clade, most appear to be bacterial, but unrelated to Roseobacter or Alpha-Proteobacterial PKSs or those derived from other Alveolates Karenia brevis or Crytosporidium parvum. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Characterization of Intracellular and Extracellular Saxitoxin Levels in Both Field and Cultured Alexandrium spp. Samples from Sequim Bay, Washington
Mar. Drugs 2008, 6(2), 103-116; doi:10.3390/md6020103
Received: 6 February 2008 / Revised: 16 April 2008 / Accepted: 18 April 2008 / Published: 14 May 2008
Cited by 37 | PDF Full-text (1088 KB) | HTML Full-text | XML Full-text
Abstract
Traditionally, harmful algal bloom studies have primarily focused on quantifying toxin levels contained within the phytoplankton cells of interest. In the case of paralytic shellfish poisoning toxins (PSTs), intracellular toxin levels and the effects of dietary consumption of toxic cells by planktivores have
[...] Read more.
Traditionally, harmful algal bloom studies have primarily focused on quantifying toxin levels contained within the phytoplankton cells of interest. In the case of paralytic shellfish poisoning toxins (PSTs), intracellular toxin levels and the effects of dietary consumption of toxic cells by planktivores have been well documented. However, little information is available regarding the levels of extracellular PSTs that may leak or be released into seawater from toxic cells during blooms. In order to fully evaluate the risks of harmful algal bloom toxins in the marine food web, it is necessary to understand all potential routes of exposure. In the present study, extracellular and intracellular PST levels were measured in field seawater samples (collected weekly from June to October 2004- 2007) and in Alexandrium spp. culture samples isolated from Sequim Bay, Washington. Measurable levels of intra- and extra-cellular toxins were detected in both field and culture samples via receptor binding assay (RBA) and an enzyme-linked immunosorbent assay (ELISA). Characterization of the PST toxin profile in the Sequim Bay isolates by preMar. column oxidation and HPLC-fluorescence detection revealed that gonyautoxin 1 and 4 made up 65 ± 9.7 % of the total PSTs present. Collectively, these data confirm that extracellular PSTs are present during blooms of Alexandrium spp. in the Sequim Bay region. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus
Mar. Drugs 2008, 6(1), 25-38; doi:10.3390/md6010025
Received: 28 November 2007 / Revised: 23 January 2008 / Accepted: 9 February 2008 / Published: 14 February 2008
Cited by 11 | PDF Full-text (3180 KB) | HTML Full-text | XML Full-text
Abstract
Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors
[...] Read more.
Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes- GFAP and the glutamate receptors including GluR 2, NMDAR 1, NMDAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk), and apoptotic genes were altered. The chemokines that were up-regulated included - IL1-a, IL-1B, IL-6, the small inducible cytokine, interferon protein IP-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all downregulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Evaluation of Harmful Algal Bloom Outreach Activities
Mar. Drugs 2007, 5(4), 208-219; doi:10.3390/md504208
Received: 30 October 2007 / Accepted: 12 December 2007 / Published: 14 December 2007
Cited by 11 | PDF Full-text (201 KB) | HTML Full-text | XML Full-text
Abstract
With an apparent increase of harmful algal blooms (HABs) worldwide,healthcare providers, public health personnel and coastal managers are struggling toprovide scientifically-based appropriately-targeted HAB outreach and education. Since1998, the Florida Poison Information Center-Miami, with its 24 hour/365 day/year freeAquatic Toxins Hotline (1-888-232-8635) available in
[...] Read more.
With an apparent increase of harmful algal blooms (HABs) worldwide,healthcare providers, public health personnel and coastal managers are struggling toprovide scientifically-based appropriately-targeted HAB outreach and education. Since1998, the Florida Poison Information Center-Miami, with its 24 hour/365 day/year freeAquatic Toxins Hotline (1-888-232-8635) available in several languages, has received over 25,000 HAB-related calls. As part of HAB surveillance, all possible cases of HAB-relatedillness among callers are reported to the Florida Health Department. This pilot studyevaluated an automated call processing menu system that allows callers to access bilingualHAB information, and to speak directly with a trained Poison Information Specialist. Themajority (68%) of callers reported satisfaction with the information, and many provided specific suggestions for improvement. This pilot study, the first known evaluation of use and satisfaction with HAB educational outreach materials, demonstrated that the automated system provided useful HAB-related information for the majority of callers, and decreased the routine informational call workload for the Poison Information Specialists, allowing them to focus on callers needing immediate assistance and their healthcare providers. These results will lead to improvement of this valuable HAB outreach, education and surveillance tool. Formal evaluation is recommended for future HAB outreach and educational materials. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Production of the Neurotoxin BMAA by a Marine Cyanobacterium
Mar. Drugs 2007, 5(4), 180-196; doi:10.3390/md504180
Received: 17 November 2007 / Accepted: 4 December 2007 / Published: 6 December 2007
Cited by 93 | PDF Full-text (1837 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
Diverse species of cyanobacteria have recently been discovered to produce theneurotoxic non-protein amino acid β-methylamino-L-alanine (BMAA). In Guam, BMAAhas been studied as a possible environmental toxin in the diets of indigenous Chamorropeople known to have high levels of Amyotrophic Lateral Sclerosis/ ParkinsonismDementia Complex
[...] Read more.
Diverse species of cyanobacteria have recently been discovered to produce theneurotoxic non-protein amino acid β-methylamino-L-alanine (BMAA). In Guam, BMAAhas been studied as a possible environmental toxin in the diets of indigenous Chamorropeople known to have high levels of Amyotrophic Lateral Sclerosis/ ParkinsonismDementia Complex (ALS/PDC). BMAA has been found to accumulate in brain tissues ofpatients with progressive neurodegenerative illness in North America. In Guam, BMAAwas found to be produced by endosymbiotic cyanobacteria of the genus Nostoc which livein specialized cycad roots. We here report detection of BMAA in laboratory cultures of afree-living marine species of Nostoc. We successfully detected BMAA in this marinespecies of Nostoc with five different methods: HPLC-FD, UPLC-UV, Amino AcidAnalyzer, LC/MS, and Triple Quadrupole LC/MS/MS. This consensus of five differentanalytical methods unequivocally demonstrates the presence of BMAA in this marinecyanobacterium. Since protein-associated BMAA can accumulate in increasing levelswithin food chains, it is possible that biomagnification of BMAA could occur in marineecosystems similar to the biomagnification of BMAA in terrestrial ecosystems. Productionof BMAA by marine cyanobacteria may represent another route of human exposure toBMAA. Since BMAA at low concentrations causes the death of motor neurons, low levelsof BMAA exposure may trigger motor neuron disease in genetically vulnerableindividuals. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Report on the First Detection of Pectenotoxin-2, Spirolide-A and Their Derivatives in French Shellfish
Mar. Drugs 2007, 5(4), 168-179; doi:10.3390/md504168
Received: 16 October 2007 / Accepted: 21 November 2007 / Published: 23 November 2007
Cited by 41 | PDF Full-text (145 KB) | HTML Full-text | XML Full-text
Abstract
In the context of the French Phytoplankton and Phycotoxins MonitoringNetwork (REPHY) programme, shellfish samples were harvested from different locationswhere harmful algae blooms were known to have occurred. For all shellfish samples foundpositive by the mouse bioassay for diarrhetic shellfish poisoning (DSP) toxins, liquidchromatography
[...] Read more.
In the context of the French Phytoplankton and Phycotoxins MonitoringNetwork (REPHY) programme, shellfish samples were harvested from different locationswhere harmful algae blooms were known to have occurred. For all shellfish samples foundpositive by the mouse bioassay for diarrhetic shellfish poisoning (DSP) toxins, liquidchromatography (LC) coupled with mass spectrometry (MS) was used to search for thefollowing lipophilic toxins: okadaic acid (OA), dinophysistoxins (DTXs), pectenotoxins(PTXs), azaspiracids (AZAs), yessotoxins (YTXs), spirolides (SPXs) and gymnodimines(GYMs). In order to investigate the presence of acyl-OAs and/or acyl-DTX-1,-2 (DTX-3),alkaline hydrolysis was performed on all samples, and LC/MS analyses were carried out onthe samples before and after hydrolysis. The results revealed different lipophilic toxinprofiles as a function of the shellfish sampling location. The primary finding was that all ofthe samples contained OA and acyl-OA. In addition, other lipophilic toxins were found inshellfish samples: DTX-2, acyl-DTX-2 and SPXs (SPX-A, SPX-desMeC) on the Atlanticcoast (Southern Brittany, Arcachon), and pectenotoxins (PTX-2, PTX-2-seco-acid and 7-epi-PTX-2-seco-acid) on the Mediterranean coast (Thau lagoon, the island of Corsica).This paper reports on the first detection of PTX-2, SPX-A and their derivatives in Frenchshellfish. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Characterization of Aerosols Containing Microcystin
Mar. Drugs 2007, 5(4), 136-150; doi:10.3390/md504136
Received: 22 September 2007 / Accepted: 10 October 2007 / Published: 12 October 2007
Cited by 23 | PDF Full-text (110 KB) | HTML Full-text | XML Full-text
Abstract
Toxic blooms of cyanobacteria are ubiquitous in both freshwater and brackishwater sources throughout the world. One class of cyanobacterial toxins, calledmicrocystins, is cyclic peptides. In addition to ingestion and dermal, inhalation is a likelyroute of human exposure. A significant increase in reporting of
[...] Read more.
Toxic blooms of cyanobacteria are ubiquitous in both freshwater and brackishwater sources throughout the world. One class of cyanobacterial toxins, calledmicrocystins, is cyclic peptides. In addition to ingestion and dermal, inhalation is a likelyroute of human exposure. A significant increase in reporting of minor symptoms,particularly respiratory symptoms was associated with exposure to higher levels ofcyanobacteria during recreational activities. Algae cells, bacteria, and waterborne toxinscan be aerosolized by a bubble-bursting process with a wind-driven white-capped wavemechanism. The purposes of this study were to: evaluate sampling and analysis techniquesfor microcystin aerosol, produce aerosol droplets containing microcystin in the laboratory,and deploy the sampling instruments in field studies. A high-volume impactor and an IOMfilter sampler were tried first in the laboratory to collect droplets containing microcystins.Samples were extracted and analyzed for microcystin using an ELISA method. Thelaboratory study showed that cyanotoxins in water could be transferred to air via a bubble-bursting process. The droplets containing microcystins showed a bimodal size distributionwith the mass median aerodynamic diameter (MMAD) of 1.4 and 27.8 μm. The samplingand analysis methods were successfully used in a pilot field study to measure microcystinaerosol in situ. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Differential Effects of Domoic Acid and E. coli Lipopolysaccharide on Tumor Necrosis Factor-α, Transforming Growth Factor-β1 and Matrix Metalloproteinase-9 Release by Rat Neonatal Microglia: Evaluation of the Direct Activation Hypothesis
Mar. Drugs 2007, 5(3), 113-135; doi:10.3390/md503113
Received: 24 August 2007 / Accepted: 20 September 2007 / Published: 24 September 2007
Cited by 5 | PDF Full-text (764 KB) | HTML Full-text | XML Full-text
Abstract
The excitatory amino acid domoic acid is the causative agent of amnesic shellfish poisoning in humans. The in vitro effects of domoic acid on rat neonatal brain microglia were compared with E. coli lipopolysaccharide (LPS), a known activator of microglia mediator release over
[...] Read more.
The excitatory amino acid domoic acid is the causative agent of amnesic shellfish poisoning in humans. The in vitro effects of domoic acid on rat neonatal brain microglia were compared with E. coli lipopolysaccharide (LPS), a known activator of microglia mediator release over a 4 to 24 hour observation period. LPS [3 ng/mL] but not domoic acid [1mM] stimulated a statistically significant increase in TNF-α mRNA and protein generation. Furthermore, both LPS and domoic acid did not significantly affect TGF- β1 gene expression and protein release. Finally, an in vitro exposure of microglia to LPS resulted in statistically significant MMP-9 expression and release, thus extending and confirming our previous observations. However, in contrast, no statistically significant increase in MMP-9 expression and release was observed after domoic acid treatment. Taken together our observations do not support the hypothesis that a short term (4 to 24 hours) in vitro exposure to domoic acid, at a concentration toxic to neuronal cells, activates rat neonatal microglia and the concomitant release of the pro-inflammatory mediators tumor necrosis factor-α (TNF-α) and matrix metalloproteinases-9 (MMP-9), as well as the anti- inflammatory cytokine transforming growth factor β1 (TGF-β1). Full article
(This article belongs to the Special Issue Marine Toxins)

Review

Jump to: Editorial, Research

Open AccessReview The Mauve Stinger Pelagia noctiluca (Forsskål, 1775). Distribution, Ecology, Toxicity and Epidemiology of Stings.
Mar. Drugs 2008, 6(3), 496-513; doi:10.3390/md6030496
Received: 12 March 2008 / Revised: 18 July 2008 / Accepted: 30 July 2008 / Published: 4 September 2008
PDF Full-text (124 KB) | HTML Full-text | XML Full-text
Abstract
The toxicity of Cnidaria is a subject of concern due to its influence on humans. In particular, jellyfish blooms can highly affect human economical activities, such as bathing, fishery, tourism, etc., as well as the public health. Stinging structures of Cnidaria (nematocysts) produce
[...] Read more.
The toxicity of Cnidaria is a subject of concern due to its influence on humans. In particular, jellyfish blooms can highly affect human economical activities, such as bathing, fishery, tourism, etc., as well as the public health. Stinging structures of Cnidaria (nematocysts) produce remarkable effects on human skin, such as erythema, swelling, burning and vesicles, and at times further severe dermonecrotic, cardio- and neurotoxic effects, which are particularly dangerous in sensitive subjects. In several zones the toxicity of jellyfish is a very important health problem, thus it has stimulated the research on these organisms; to date toxicological research on Cnidarian venoms in the Mediterranean region is not well developed due to the weak poisonousness of venoms of jellyfish and anemones living in this area. In spite of this, during last decades several problems were also caused in the Mediterranean by stinging consequent to Cnidarian blooms mainly caused by Pelagia noctiluca (Forsskål, 1775) which is known to be the most venomous Mediterranean jellyfish. This paper reviews the knowledge on this jellyfish species, particularly considering its occurrence and toxicity. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Ciguatera Fish Poisoning: Treatment, Prevention and Management
Mar. Drugs 2008, 6(3), 456-479; doi:10.3390/md6030456
Received: 28 February 2008 / Revised: 24 July 2008 / Accepted: 19 August 2008 / Published: 21 August 2008
Cited by 79 | PDF Full-text (697 KB) | HTML Full-text | XML Full-text
Abstract
Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world, and it causes substantial physical and functional impact. It produces a myriad of gastrointestinal, neurologic and/or cardiovascular symptoms which last days to weeks, or even months. Although there are
[...] Read more.
Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world, and it causes substantial physical and functional impact. It produces a myriad of gastrointestinal, neurologic and/or cardiovascular symptoms which last days to weeks, or even months. Although there are reports of symptom amelioration with some interventions (e.g. IV mannitol), the appropriate treatment for CFP remains unclear to many physicians. We review the literature on the treatments for CFP, including randomized controlled studies and anecdotal reports. The article is intended to clarify treatment options, and provide information about management and prevention of CFP, for emergency room physicians, poison control information providers, other health care providers, and patients. Full article
(This article belongs to the Special Issue Marine Toxins)
Figures

Open AccessReview Neurotoxic Shellfish Poisoning
Mar. Drugs 2008, 6(3), 431-455; doi:10.3390/md6030431
Received: 26 February 2008 / Revised: 17 June 2008 / Accepted: 24 June 2008 / Published: 12 July 2008
Cited by 89 | PDF Full-text (360 KB) | HTML Full-text | XML Full-text
Abstract
Neurotoxic shellfish poisoning (NSP) is caused by consumption of molluscan shellfish contaminated with brevetoxins primarily produced by the dinoflagellate, Karenia brevis. Blooms of K. brevis, called Florida red tide, occur frequently along the Gulf of Mexico. Many shellfish beds in the
[...] Read more.
Neurotoxic shellfish poisoning (NSP) is caused by consumption of molluscan shellfish contaminated with brevetoxins primarily produced by the dinoflagellate, Karenia brevis. Blooms of K. brevis, called Florida red tide, occur frequently along the Gulf of Mexico. Many shellfish beds in the US (and other nations) are routinely monitored for presence of K. brevis and other brevetoxin-producing organisms. As a result, few NSP cases are reported annually from the US. However, infrequent larger outbreaks do occur. Cases are usually associated with recreationally-harvested shellfish collected during or post red tide blooms. Brevetoxins are neurotoxins which activate voltage-sensitive sodium channels causing sodium influx and nerve membrane depolarization. No fatalities have been reported, but hospitalizations occur. NSP involves a cluster of gastrointestinal and neurological symptoms: nausea and vomiting, paresthesias of the mouth, lips and tongue as well as distal paresthesias, ataxia, slurred speech and dizziness. Neurological symptoms can progress to partial paralysis; respiratory distress has been recorded. Recent research has implicated new species of harmful algal bloom organisms which produce brevetoxins, identified additional marine species which accumulate brevetoxins, and has provided additional information on the toxicity and analysis of brevetoxins. A review of the known epidemiology and recommendations for improved NSP prevention are presented. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Neurotoxins from Marine Dinoflagellates: A Brief Review
Mar. Drugs 2008, 6(2), 349-371; doi:10.3390/md6020349
Received: 9 March 2008 / Revised: 14 May 2008 / Accepted: 14 May 2008 / Published: 11 June 2008
Cited by 111 | PDF Full-text (521 KB) | HTML Full-text | XML Full-text
Abstract
Dinoflagellates are not only important marine primary producers and grazers, but also the major causative agents of harmful algal blooms. It has been reported that many dinoflagellate species can produce various natural toxins. These toxins can be extremely toxic and many of them
[...] Read more.
Dinoflagellates are not only important marine primary producers and grazers, but also the major causative agents of harmful algal blooms. It has been reported that many dinoflagellate species can produce various natural toxins. These toxins can be extremely toxic and many of them are effective at far lower dosages than conventional chemical agents. Consumption of seafood contaminated by algal toxins results in various seafood poisoning syndromes: paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP), diarrheic shellfish poisoning (DSP), ciguatera fish poisoning (CFP) and azaspiracid shellfish poisoning (ASP). Most of these poisonings are caused by neurotoxins which present themselves with highly specific effects on the nervous system of animals, including humans, by interfering with nerve impulse transmission. Neurotoxins are a varied group of compounds, both chemically and pharmacologically. They vary in both chemical structure and mechanism of action, and produce very distinct biological effects, which provides a potential application of these toxins in pharmacology and toxicology. This review summarizes the origin, structure and clinical symptoms of PSP, NSP, CFP, AZP, yessotoxin and palytoxin produced by marine dinoflagellates, as well as their molecular mechanisms of action on voltage-gated ion channels. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Non-Traditional Vectors for Paralytic Shellfish Poisoning
Mar. Drugs 2008, 6(2), 308-348; doi:10.3390/md6020308
Received: 14 March 2008 / Revised: 3 June 2008 / Accepted: 3 June 2008 / Published: 10 June 2008
Cited by 76 | PDF Full-text (984 KB) | HTML Full-text | XML Full-text
Abstract
Paralytic shellfish poisoning (PSP), due to saxitoxin and related compounds, typically results from the consumption of filter-feeding molluscan shellfish that concentrate toxins from marine dinoflagellates. In addition to these microalgal sources, saxitoxin and related compounds, referred to in this review as STXs, are
[...] Read more.
Paralytic shellfish poisoning (PSP), due to saxitoxin and related compounds, typically results from the consumption of filter-feeding molluscan shellfish that concentrate toxins from marine dinoflagellates. In addition to these microalgal sources, saxitoxin and related compounds, referred to in this review as STXs, are also produced in freshwater cyanobacteria and have been associated with calcareous red macroalgae. STXs are transferred and bioaccumulate throughout aquatic food webs, and can be vectored to terrestrial biota, including humans. Fisheries closures and human intoxications due to STXs have been documented in several non-traditional (i.e. non-filter-feeding) vectors. These include, but are not limited to, marine gastropods, both carnivorous and grazing, crustacea, and fish that acquire STXs through toxin transfer. Often due to spatial, temporal, or a species disconnection from the primary source of STXs (bloom forming dinoflagellates), monitoring and management of such non-traditional PSP vectors has been challenging. A brief literature review is provided for filter feeding (traditional) and nonfilter feeding (non-traditional) vectors of STXs with specific reference to human effects. We include several case studies pertaining to management actions to prevent PSP, as well as food poisoning incidents from STX(s) accumulation in non-traditional PSP vectors. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview In Utero Domoic Acid Toxicity: A Fetal Basis to Adult Disease in the California Sea Lion (Zalophus californianus)
Mar. Drugs 2008, 6(2), 262-290; doi:10.3390/md6020262
Received: 28 February 2008 / Revised: 26 May 2008 / Accepted: 29 May 2008 / Published: 6 June 2008
Cited by 39 | PDF Full-text (7656 KB) | HTML Full-text | XML Full-text
Abstract
California sea lions have been a repeated subject of investigation for early life toxicity, which has been documented to occur with increasing frequency from late February through mid-May in association with organochlorine (PCB and DDT) poisoning and infectious disease in the 1970's and
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California sea lions have been a repeated subject of investigation for early life toxicity, which has been documented to occur with increasing frequency from late February through mid-May in association with organochlorine (PCB and DDT) poisoning and infectious disease in the 1970's and domoic acid poisoning in the last decade. The mass early life mortality events result from the concentrated breeding grounds and synchronization of reproduction over a 28 day post partum estrus cycle and 11 month in utero phase. This physiological synchronization is triggered by a decreasing photoperiod of 11.48 h/day that occurs approximately 90 days after conception at the major California breeding grounds. The photoperiod trigger activates implantation of embryos to proceed with development for the next 242 days until birth. Embryonic diapause is a selectable trait thought to optimize timing for food utilization and male migratory patterns; yet from the toxicological perspective presented here also serves to synchronize developmental toxicity of pulsed environmental events such as domoic acid poisoning. Research studies in laboratory animals have defined age-dependent neurotoxic effects during development and windows of susceptibility to domoic acid exposure. This review will evaluate experimental domoic acid neurotoxicity in developing rodents and, aided by comparative allometric projections, will analyze potential prenatal toxicity and exposure susceptibility in the California sea lion. This analysis should provide a useful tool to forecast fetal toxicity and understand the impact of fetal toxicity on adult disease of the California sea lion. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Domoic Acid Toxicologic Pathology: A Review
Mar. Drugs 2008, 6(2), 180-219; doi:10.3390/md6020180
Received: 4 December 2007 / Revised: 16 May 2008 / Accepted: 16 May 2008 / Published: 28 May 2008
Cited by 74 | PDF Full-text (2664 KB) | HTML Full-text | XML Full-text
Abstract
Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among
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Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among the most prominent features described was memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic acid is produced by certain marine organisms, such as the red alga Chondria armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987, monitoring programs have been successful in preventing other human incidents of ASP. However, there are documented cases of domoic acid intoxication in wild animals and outbreaks of coastal water contamination in many regions world-wide. Hence domoic acid continues to pose a global risk to the health and safety of humans and wildlife. Several mechanisms have been implicated as mediators for the effects of domoic acid. Of particular importance is the role played by glutamate receptors as mediators of excitatory neurotransmission and the demonstration of a wide distribution of these receptors outside the central nervous system, prompting the attention to other tissues as potential target sites. The aim of this document is to provide a comprehensive review of ASP, DOM induced pathology including ultrastructural changes associated to subchronic oral exposure, and discussion of key proposed mechanisms of cell/tissue injury involved in DOM induced brain pathology and considerations relevant to food safety and human health. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Tetrodotoxin – Distribution and Accumulation in Aquatic Organisms, and Cases of Human Intoxication
Mar. Drugs 2008, 6(2), 220-242; doi:10.3390/md6020220
Received: 23 December 2007 / Revised: 24 March 2008 / Accepted: 8 April 2008 / Published: 28 May 2008
Cited by 123 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of
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Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Mycosporine-Like Amino Acids and Marine Toxins - The Common and the Different
Mar. Drugs 2008, 6(2), 147-163; doi:10.3390/md6020147
Received: 7 March 2008 / Revised: 9 May 2008 / Accepted: 13 May 2008 / Published: 22 May 2008
Cited by 26 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text
Abstract
Marine microorganisms harbor a multitude of secondary metabolites. Among these are toxins of different chemical classes as well as the UV-protective mycosporinelike amino acids (MAAs). The latter form a group of water-soluble, low molecular-weight (generally
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Marine microorganisms harbor a multitude of secondary metabolites. Among these are toxins of different chemical classes as well as the UV-protective mycosporinelike amino acids (MAAs). The latter form a group of water-soluble, low molecular-weight (generally < 400) compounds composed of either an aminocyclohexenone or an aminocyclohexenimine ring, carrying amino acid or amino alcohol substituents. So far there has been no report of toxicity in MAAs but nevertheless there are some features they have in common with marine toxins. Among the organisms producing MAAs are cyanobacteria, dinoflagellates and diatoms that also synthesize toxins. As in cyclic peptide toxins found in cyanobacteria, amino acids are the main building blocks of MAAs. Both, MAAs and some marine toxins are transferred to other organisms e.g. via the food chains, and chemical modifications can take place in secondary consumers. In contrast to algal toxins, the physiological role of MAAs is clearly the protection from harmful UV radiation by physical screening. However, other roles, e.g. as osmolytes and antioxidants, are also considered. In this paper the common characteristics of MAAs and marine toxins are discussed as well as the differences. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Cyanobacterial Toxins as Allelochemicals with Potential Applications as Algaecides, Herbicides and Insecticides
Mar. Drugs 2008, 6(2), 117-146; doi:10.3390/md6020117
Received: 27 February 2008 / Revised: 1 May 2008 / Accepted: 12 May 2008 / Published: 15 May 2008
Cited by 64 | PDF Full-text (344 KB) | HTML Full-text | XML Full-text
Abstract
Cyanobacteria (“blue-green algae”) from marine and freshwater habitats are known to produce a diverse array of toxic or otherwise bioactive metabolites. However, the functional role of the vast majority of these compounds, particularly in terms of the physiology and ecology of the cyanobacteria
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Cyanobacteria (“blue-green algae”) from marine and freshwater habitats are known to produce a diverse array of toxic or otherwise bioactive metabolites. However, the functional role of the vast majority of these compounds, particularly in terms of the physiology and ecology of the cyanobacteria that produce them, remains largely unknown. A limited number of studies have suggested that some of the compounds may have ecological roles as allelochemicals, specifically including compounds that may inhibit competing sympatric macrophytes, algae and microbes. These allelochemicals may also play a role in defense against potential predators and grazers, particularly aquatic invertebrates and their larvae. This review will discuss the existing evidence for the allelochemical roles of cyanobacterial toxins, as well as the potential for development and application of these compounds as algaecides, herbicides and insecticides, and specifically present relevant results from investigations into toxins of cyanobacteria from the Florida Everglades and associated waterways. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Azaspiracid Shellfish Poisoning: A Review on the Chemistry, Ecology, and Toxicology with an Emphasis on Human Health Impacts
Mar. Drugs 2008, 6(2), 39-72; doi:10.3390/md6020039
Received: 30 November 2007 / Revised: 21 February 2008 / Accepted: 18 March 2008 / Published: 7 May 2008
Cited by 89 | PDF Full-text (566 KB) | HTML Full-text | XML Full-text
Abstract
Azaspiracids (AZA) are polyether marine toxins that accumulate in various shellfish species and have been associated with severe gastrointestinal human intoxications since 1995. This toxin class has since been reported from several countries, including Morocco and much of western Europe. A regulatory limit
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Azaspiracids (AZA) are polyether marine toxins that accumulate in various shellfish species and have been associated with severe gastrointestinal human intoxications since 1995. This toxin class has since been reported from several countries, including Morocco and much of western Europe. A regulatory limit of 160 μg AZA/kg whole shellfish flesh was established by the EU in order to protect human health; however, in some cases, AZA concentrations far exceed the action level. Herein we discuss recent advances on the chemistry of various AZA analogs, review the ecology of AZAs, including the putative progenitor algal species, collectively interpret the in vitro and in vivo data on the toxicology of AZAs relating to human health issues, and outline the European legislature associated with AZAs. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Yessotoxins, a Group of Marine Polyether Toxins: an Overview
Mar. Drugs 2008, 6(2), 73-102; doi:10.3390/md6020073
Received: 5 December 2007 / Revised: 27 February 2008 / Accepted: 5 March 2008 / Published: 7 May 2008
Cited by 61 | PDF Full-text (383 KB) | HTML Full-text | XML Full-text
Abstract
Yessotoxin (YTX) is a marine polyether toxin that was first isolated in 1986 from the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic shellfish
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Yessotoxin (YTX) is a marine polyether toxin that was first isolated in 1986 from the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic shellfish poisoning (DSP) because they are often simultaneously extracted with DSP toxins, and give positive results when tested in the conventional mouse bioassay for DSP toxins. However, recent evidence suggests that YTXs should be excluded from the DSP toxins group, because unlike okadaic acid (OA) and dinophyisistoxin-1 (DTX-1), YTXs do not cause either diarrhea or inhibition of protein phosphatases . In spite of the increasing number of molecular studies focused on the toxicity of YTX, the precise mechanism of action is currently unknown. Since the discovery of YTX, almost forty new analogues isolated from both mussels and dinoflagellates have been characterized by NMR or LC-MS/MS techniques. These studies indicate a wide variability in the profile and the relative abundance of YTXs in both, bivalves and dinoflagellates. This review covers current knowledge on the origin, producer organisms and vectors, chemical structures, metabolism, biosynthetic origin, toxicological properties, potential risks to human health and advances in detection methods of YTXs. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Mechanisms of Toxicity of 3-Alkylpyridinium Polymers from Marine Sponge Reniera sarai
Mar. Drugs 2007, 5(4), 157-167; doi:10.3390/MD504157
Received: 16 October 2007 / Accepted: 31 October 2007 / Published: 13 November 2007
Cited by 24 | PDF Full-text (89 KB) | HTML Full-text | XML Full-text
Abstract
Polymeric 3-alkylpyridinium salts (poly-APS) present in the marine spongeReniera sarai show a broad spectrum of biological activities. They are lytic to erythrocytesand various other mammalian cells, enabling the transfection of the latter with alien DNA.Furthermore, they show inhibitory effects to marine bacteria and
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Polymeric 3-alkylpyridinium salts (poly-APS) present in the marine spongeReniera sarai show a broad spectrum of biological activities. They are lytic to erythrocytesand various other mammalian cells, enabling the transfection of the latter with alien DNA.Furthermore, they show inhibitory effects to marine bacteria and can inhibit fouling ofmicro- and macroorganisms to submerged surfaces. Finally, poly-APS act as potentcholinesterase inhibitors. The kinetics of acetylcholinesterase inhibition by poly-APS invitro is complex and comprises several successive phases ending in irreversible inhibitionof the enzyme. The latter is accounted for by aggregation and precipitation of the enzyme-inhibitor complexes. Poly-APS are lethal to rats in concentrations above 2.7 mg/kg.Monitoring of the basic vital functions and histopathological analysis showed that theeffects directly ascribable to acetylcholinesterase inhibition are only observed afterapplication of lower concentrations of poly-APS. At higher concentrations, such effectswere masked by other, more pronounced and faster developing lethal effects of the toxin,such as haemolysis and platelet aggregation. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessReview Molecular Structure of Endotoxins from Gram-negative Marine Bacteria: An Update
Mar. Drugs 2007, 5(3), 85-112; doi:10.3390/md503085
Received: 27 August 2007 / Accepted: 17 September 2007 / Published: 19 September 2007
Cited by 33 | PDF Full-text (187 KB) | HTML Full-text | XML Full-text
Abstract
Marine bacteria are microrganisms that have adapted, through millions of years, to survival in environments often characterized by one or more extreme physical or chemical parameters, namely pressure, temperature and salinity. The main interest in the research on marine bacteria is due to
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Marine bacteria are microrganisms that have adapted, through millions of years, to survival in environments often characterized by one or more extreme physical or chemical parameters, namely pressure, temperature and salinity. The main interest in the research on marine bacteria is due to their ability to produce several biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents. Nonetheless, lipopolysaccharides (LPSs), or their portions, from Gram-negative marine bacteria, have often shown low virulence, and represent potential candidates in the development of drugs to prevent septic shock. Besides, the molecular architecture of such molecules is related to the possibility of thriving in marine habitats, shielding the cell from the disrupting action of natural stress factors. Over the last few years, the depiction of a variety of structures of lipids A, core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been given. In particular, here we will examine the most recently encountered structures for bacteria belonging to the genera Shewanella, Pseudoalteromonas and Alteromonas, of the γ-Proteobacteria phylum, and to the genera Flavobacterium, Cellulophaga, Arenibacter and Chryseobacterium, of the Cytophaga- Flavobacterium-Bacteroides phylum. Particular attention will be paid to the chemical features expressed by these structures (characteristic monosaccharides, non-glycidic appendages, phosphate groups), to the typifying traits of LPSs from marine bacteria and to the possible correlation existing between such features and the adaptation, over years, of bacteria to marine environments. Full article
(This article belongs to the Special Issue Marine Toxins)

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