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  1. Article ; Online: Neurological disease rises from ocean to bring model for human epilepsy to life.

    Ramsdell, John S

    Toxins

    2010  Volume 2, Issue 7, Page(s) 1646–1675

    Abstract: Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had ... ...

    Abstract Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages.
    MeSH term(s) Animals ; DDT/toxicity ; Disease Models, Animal ; Epilepsy/chemically induced ; Humans ; Kainic Acid/analogs & derivatives ; Kainic Acid/toxicity ; Marine Toxins/toxicity ; Neurotoxins/toxicity ; Pesticides/toxicity ; Water Pollutants, Chemical/toxicity
    Chemical Substances Marine Toxins ; Neurotoxins ; Pesticides ; Water Pollutants, Chemical ; DDT (CIW5S16655) ; domoic acid (M02525818H) ; Kainic Acid (SIV03811UC)
    Language English
    Publishing date 2010-06-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins2071646
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Sample preparation and liquid chromatography-tandem mass spectrometry for the analysis of selected Pacific ciguatoxins in blood samples.

    Wang, Zhihong / Fuquay, Jennifer Maucher / Ledreux, Aurelie / Barbieri, Michelle / Ramsdell, John S

    Journal of chromatography. A

    2020  Volume 1621, Page(s) 461050

    Abstract: Consumption of ciguatoxin-contaminated seafood can lead to ciguatera poisoning (CP). The diagnosis of CP in humans is based on the clinical symptoms after eating the fish from tropical or subtropical areas because no confirmatory clinical tests are ... ...

    Abstract Consumption of ciguatoxin-contaminated seafood can lead to ciguatera poisoning (CP). The diagnosis of CP in humans is based on the clinical symptoms after eating the fish from tropical or subtropical areas because no confirmatory clinical tests are available. One of the challenges for ciguatoxin analysis is their extremely low but toxicologically relevant concentration in biological samples. We previously reported a method using acetonitrile to precipitate proteins and extract the ciguatoxins simultaneously in whole blood samples from animals for toxin quantification by N2A cell-based assay. However, a test method for unambiguous confirmation of exposure of marine animals or humans to ciguatoxins is still needed. In the present study, we adopted the acetonitrile extraction method and added sample clean-up in the sample preparation for the determination of Pacific ciguatoxins CTX1B (aka P-CTX-1), 52-epi-54-deoxyCTX1B (aka P-CTX-2), and CTX3C (aka P-CTX-3C) in blood plasma by LC-MS/MS. We investigated sample clean-up, LC mobile phases, LC solvent programming, and settings of the two mass spectrometers (4000 Q TRAP and AB SCIEX Triple Quad 5500) in order to improve the ability to detect the Pacific ciguatoxins at ppt level. Rat blood plasma was used for the method development. Average recoveries of the three toxins in the rat plasma samples ranged from 90% to 116% with relative standard deviations of less than 15%. The method detection limits were still not low enough for the determination of the Pacific ciguatoxins in individual blood samples from Hawaiian monk seals with the two LC-MS systems. The methods were applied to a pooled sample of blood plasma collected from Hawaiian monk seals for confirmation of toxin exposure. This study will benefit monitoring of Pacific ciguatoxins in marine mammals and potentially humans by LC-MS/MS.
    MeSH term(s) Acetonitriles/chemistry ; Animals ; Chromatography, Liquid/methods ; Ciguatoxins/blood ; Limit of Detection ; Rats ; Seals, Earless/blood ; Solvents ; Tandem Mass Spectrometry/methods
    Chemical Substances Acetonitriles ; Solvents ; Ciguatoxins (11050-21-8) ; acetonitrile (Z072SB282N)
    Language English
    Publishing date 2020-03-16
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1171488-8
    ISSN 1873-3778 ; 0021-9673
    ISSN (online) 1873-3778
    ISSN 0021-9673
    DOI 10.1016/j.chroma.2020.461050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Domoic acid epileptic disease.

    Ramsdell, John S / Gulland, Frances M

    Marine drugs

    2014  Volume 12, Issue 3, Page(s) 1185–1207

    Abstract: Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic ... ...

    Abstract Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis.
    MeSH term(s) Aged ; Aged, 80 and over ; Aging/physiology ; Amnesia/chemically induced ; Amnesia/psychology ; Animal Diseases/chemically induced ; Animal Diseases/diagnosis ; Animal Diseases/physiopathology ; Animals ; Behavior, Animal/drug effects ; Bivalvia ; Epilepsy/chemically induced ; Epilepsy/diagnosis ; Epilepsy/veterinary ; Epilepsy, Temporal Lobe/chemically induced ; Epilepsy, Temporal Lobe/physiopathology ; Female ; Food Contamination ; Hippocampus/physiopathology ; Humans ; Kainic Acid/analogs & derivatives ; Kainic Acid/poisoning ; Male ; Marine Toxins/poisoning ; Middle Aged ; Neuromuscular Depolarizing Agents/poisoning ; Neurotoxins/poisoning ; Olfactory Pathways/physiopathology ; Rats ; Recurrence ; Sea Lions/physiology ; Seizures/chemically induced ; Seizures/diagnosis ; Seizures/veterinary ; Shellfish Poisoning/diagnosis ; Shellfish Poisoning/physiopathology ; Shellfish Poisoning/veterinary
    Chemical Substances Marine Toxins ; Neuromuscular Depolarizing Agents ; Neurotoxins ; domoic acid (M02525818H) ; Kainic Acid (SIV03811UC)
    Language English
    Publishing date 2014-03-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2175190-0
    ISSN 1660-3397 ; 1660-3397
    ISSN (online) 1660-3397
    ISSN 1660-3397
    DOI 10.3390/md12031185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Bioavailability and intravenous toxicokinetic parameters for Pacific ciguatoxin P-CTX-1 in rats.

    Ledreux, Aurélie / Ramsdell, John S

    Toxicon : official journal of the International Society on Toxinology

    2013  Volume 64, Page(s) 81–86

    Abstract: Ciguatoxins are sodium channel activator toxins responsible for ciguatera fish poisoning. In this study, we determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0.13 ng P-CTX-1 per g of body ... ...

    Abstract Ciguatoxins are sodium channel activator toxins responsible for ciguatera fish poisoning. In this study, we determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0.13 ng P-CTX-1 per g of body weight. The ciguatoxin activity was assessed over time in blood using the sensitive functional Neuro2a assay. The data were analyzed with a two-compartmental model. After exposure, the ciguatoxin activity exhibited a rapid (alpha half-life of 6 min) and extensive distribution into tissues (apparent steady state volume of distribution of 7.8 L). Ciguatoxin elimination from blood was slower with a beta half-life estimated at 35.5 h. The toxicokinetic parameters determined from this study were compared to data previously obtained after oral and intraperitoneal exposure of rats to 0.26 ng P-CTX-1 per g of body weight. Maximal bioavailability was determined by the area under the concentration curve, and was used to calculate the absolute P-CTX-1 bioavailabilities for oral and intraperitoneal routes of exposures of 39% and 75%, respectively.
    MeSH term(s) Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Cell Line, Tumor ; Cell Survival/drug effects ; Ciguatera Poisoning/chemically induced ; Ciguatera Poisoning/metabolism ; Ciguatoxins/administration & dosage ; Ciguatoxins/pharmacokinetics ; Ciguatoxins/toxicity ; Half-Life ; Injections, Intraperitoneal ; Injections, Intravenous ; Male ; Mice ; Neuroblastoma/drug therapy ; Neuroblastoma/pathology ; Rats ; Rats, Sprague-Dawley ; Sodium Channels/drug effects
    Chemical Substances Sodium Channels ; Ciguatoxins (11050-21-8)
    Language English
    Publishing date 2013-03-15
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 204479-1
    ISSN 1879-3150 ; 0041-0101
    ISSN (online) 1879-3150
    ISSN 0041-0101
    DOI 10.1016/j.toxicon.2012.12.026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Persistent neurological damage associated with spontaneous recurrent seizures and atypical aggressive behavior of domoic acid epileptic disease.

    Tiedeken, Jessica A / Ramsdell, John S

    Toxicological sciences : an official journal of the Society of Toxicology

    2013  Volume 133, Issue 1, Page(s) 133–143

    Abstract: The harmful alga Pseudo-nitzschia sp. is the cause of human amnesic shellfish poisoning and the stranding of thousands of sea lions with seizures as a hallmark symptom. A human case study and epidemiological report of hundreds of stranded sea lions found ...

    Abstract The harmful alga Pseudo-nitzschia sp. is the cause of human amnesic shellfish poisoning and the stranding of thousands of sea lions with seizures as a hallmark symptom. A human case study and epidemiological report of hundreds of stranded sea lions found individuals presenting months after recovery with a neurological disease similar to temporal lobe epilepsy. A rat model developed to establish and better predict how epileptic disease results from domoic acid poisoning demonstrated that a single episode of status epilepticus (SE), after a latent period, leads to a progressive state of spontaneous recurrent seizure (SRS) and expression of atypical aggressive behaviors. Structural damage associated with domoic acid-induced SE is prominent in olfactory pathways. Here, we examine structural damage in seven rats that progressed to epileptic disease. Diseased animals show progressive neuronal loss in the piriform cortex and degeneration of terminal fields in these layers and the posteromedial cortical amygdaloid nucleus. Animals that display aggressive behavior had additional neuronal damage to the anterior olfactory cortex. This study provides insight into the structural basis for the progression of domoic acid epileptic disease and relates to the California sea lion, where poisoned animals progress to a disease characterized by SRS and aggressive behaviors.
    MeSH term(s) Aggression/drug effects ; Animals ; Brain/drug effects ; Brain/pathology ; Cell Count ; Disease Models, Animal ; Kainic Acid/analogs & derivatives ; Kainic Acid/poisoning ; Male ; Neurons/drug effects ; Neurons/pathology ; Rats ; Rats, Sprague-Dawley ; Recurrence ; Seizures/chemically induced ; Seizures/pathology ; Seizures/psychology ; Status Epilepticus/chemically induced ; Status Epilepticus/pathology ; Status Epilepticus/psychology
    Chemical Substances domoic acid (M02525818H) ; Kainic Acid (SIV03811UC)
    Language English
    Publishing date 2013-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kft037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Analysis of diarrhetic shellfish poisoning toxins and pectenotoxin-2 in the bottlenose dolphin (Tursiops truncatus) by liquid chromatography-tandem mass spectrometry.

    Wang, Zhihong / Broadwater, Margaret H / Ramsdell, John S

    Journal of chromatography. A

    2015  Volume 1416, Page(s) 22–30

    Abstract: Toxins produced by harmful algae are associated with detrimental health effects and mass mortalities of marine mammals. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is generally used to confirm the presence of algal toxins in marine mammals. ...

    Abstract Toxins produced by harmful algae are associated with detrimental health effects and mass mortalities of marine mammals. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is generally used to confirm the presence of algal toxins in marine mammals. Sample preparation and LC-MS/MS methods for the determination of three diarrhetic shellfish poisoning (DSP) toxins (okadaic acid, OA; dinophysistoxin-1, DTX1; dinophysistoxin-2, DTX2) and pectenotoxin-2 (PTX2) in bottlenose dolphin (Tursiops truncatus) urine and tissue samples were evaluated using spike-and-recovery tests. Sample clean-up with either reversed-phase silica or polymeric solid-phase extraction (SPE) reduced interference of sample matrices and improved toxin recoveries, with polymeric SPE showing higher sample loading capacity. LC separation on Xbridge C18 columns using acetonitrile/water gradient elutions with ammonia as the additive was chosen for its high detectivity and sensitivity in the MS detection of DSP toxins in negative ion mode. The retention times of OA, DTX1, and DTX2, separated as negative ions, increased with LC column temperature while the retention time of PTX2, separated as the neutral molecule, was weakly affected. At the same column temperature, retention times of OA, DTX1, and DTX2 gradually increased as the mobile phases aged while the retention time of PTX2 remained unchanged; higher column temperatures resulted in a greater increase in the retention time of each DSP toxin with mobile phase aging. Average recoveries of the 4 toxins in bottlenose dolphin samples ranged from 80% to 130% with relative standard deviations of less than 15% using the LC mobile phases prepared within one week at a column temperature of 30°C or 40°C. The preferred column temperature was 30°C, as the retention times of DSP toxins were less affected by mobile phase aging at this temperature. The limit of detection of each toxin analyzed in bottlenose dolphin samples was 2.8 ng/g or less in tissue samples and 0.7 ng/ml or less in urine.
    MeSH term(s) Animals ; Bottle-Nosed Dolphin/metabolism ; Chromatography, Liquid/methods ; Diarrhea/chemically induced ; Furans/analysis ; Marine Toxins/analysis ; Okadaic Acid/analysis ; Pyrans/analysis ; Shellfish Poisoning/metabolism ; Solid Phase Extraction/methods ; Tandem Mass Spectrometry/methods
    Chemical Substances Furans ; Marine Toxins ; Pyrans ; Okadaic Acid (1W21G5Q4N2) ; dinophysistoxin 1 (4Q51CVY9O2) ; pectenotoxin 2 (97564-91-5) ; dinophysistoxin 2 (RH78DHY1JZ)
    Language English
    Publishing date 2015-10-16
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1171488-8
    ISSN 1873-3778 ; 0021-9673
    ISSN (online) 1873-3778
    ISSN 0021-9673
    DOI 10.1016/j.chroma.2015.08.066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Domoic acid induced seizures progress to a chronic state of epilepsy in rats.

    Muha, Noah / Ramsdell, John S

    Toxicon : official journal of the International Society on Toxinology

    2011  Volume 57, Issue 1, Page(s) 168–171

    Abstract: The emergence of an epilepsy syndrome in sea lions poisoned by domoic acid (DA) draws striking parallels to the single case study of temporal lobe epilepsy (TLE) that developed in an 84 yr old man one year after being poisoned by DA. To establish a basis ...

    Abstract The emergence of an epilepsy syndrome in sea lions poisoned by domoic acid (DA) draws striking parallels to the single case study of temporal lobe epilepsy (TLE) that developed in an 84 yr old man one year after being poisoned by DA. To establish a basis for understanding this disease in sea lions and humans that appears to progress from DA poisoning, we have investigated the potential for a single incident of DA poisoning in rats to progress to spontaneous recurrent seizures (SRS), the hallmark of epilepsy. We have developed a DA administration protocol to induce a nonlethal status epilepticus (SE) and monitored the animals for SRS by 6 h/week of video recording. We demonstrate that a single episode of SE leads to SRS in 94% of rats (n = 23) in 6 months. These findings indicate that DA induced SE can efficiently translate to epileptic disease.
    MeSH term(s) Animals ; Disease Models, Animal ; Disease Progression ; Epilepsy/chemically induced ; Epilepsy/physiopathology ; Kainic Acid/analogs & derivatives ; Kainic Acid/toxicity ; Male ; Marine Toxins/toxicity ; Neurotoxins/toxicity ; Rats ; Rats, Sprague-Dawley ; Seizures/chemically induced ; Seizures/physiopathology ; Videotape Recording
    Chemical Substances Marine Toxins ; Neurotoxins ; domoic acid (M02525818H) ; Kainic Acid (SIV03811UC)
    Language English
    Publishing date 2011-01
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 204479-1
    ISSN 1879-3150 ; 0041-0101
    ISSN (online) 1879-3150
    ISSN 0041-0101
    DOI 10.1016/j.toxicon.2010.07.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Analysis of interactions of brevetoxin-B and human serum albumin by liquid chromatography/mass spectrometry.

    Wang, Zhihong / Ramsdell, John S

    Chemical research in toxicology

    2011  Volume 24, Issue 1, Page(s) 54–64

    Abstract: Brevetoxins are neurotoxins produced by marine dinoflagellates, primarily Karenia brevis, and can cause intoxication and even mortality of marine species, affect human health through the consumption of brevetoxin-contaminated shellfish, and effect ... ...

    Abstract Brevetoxins are neurotoxins produced by marine dinoflagellates, primarily Karenia brevis, and can cause intoxication and even mortality of marine species, affect human health through the consumption of brevetoxin-contaminated shellfish, and effect respiratory irritation through aerosol exposure at coastal areas. Brevetoxin-A and brevetoxin-B, the major brevetoxins produced in algae, are metabolized to a series of amino acid and peptide-related derivatives in shellfish through the reactions of the amino acid residue cysteine with an α,β-unsaturated aldehyde group. In this paper, covalent interactions between brevetoxin and proteins were investigated using brevetoxin-B and human serum albumin (HSA) as a model. It is demonstrated that both noncovalent and covalent interactions can occur between brevetoxin-B and HSA with in vitro experiments. Covalent adducts of brevetoxin-B and HSA were generated under physiological conditions and reduced with sodium borohydride based on the reaction conditions of single amino acid residues with brevetoxin-B. LC/MS analysis of toxin-treated HSA recognized the formation of the intact protein adducts with primarily one and two toxin molecules attached to one HSA molecule. HSA treated with/without brevetoxin-B was digested with trypsin, trypsin following chymotrypsin, and Pronase, respectively, for LC/MS analysis of adduction sites. Brevetoxin-B was found to react primarily with Cys(34) and His(3) and with His and Lys at other sites of HSA with variable reactivity and with Lys in general the least reactive.
    MeSH term(s) Chromatography, High Pressure Liquid ; Chymotrypsin/metabolism ; Cysteine/chemistry ; Dinoflagellida/metabolism ; Histidine/chemistry ; Humans ; Marine Toxins/chemistry ; Marine Toxins/toxicity ; Mass Spectrometry ; Oxocins/chemistry ; Oxocins/toxicity ; Pronase/metabolism ; Protein Binding ; Serum Albumin/chemistry ; Serum Albumin/metabolism ; Trypsin/metabolism
    Chemical Substances Marine Toxins ; Oxocins ; Serum Albumin ; Histidine (4QD397987E) ; brevetoxin B (79580-28-2) ; Chymotrypsin (EC 3.4.21.1) ; Trypsin (EC 3.4.21.4) ; Pronase (EC 3.4.24.-) ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2011-01-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/tx1002854
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Neurological Disease Rises from Ocean to Bring Model for Human Epilepsy to Life

    John S. Ramsdell

    Toxins, Vol 2, Iss 7, Pp 1646-

    2010  Volume 1675

    Abstract: Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had ... ...

    Abstract Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages.
    Keywords domoic acid ; harmful algal bloom ; dichlorodiphenyltrichloroethane (DDT) ; sea lion ; epilepsy ; Medicine ; R
    Subject code 551
    Language English
    Publishing date 2010-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Tissue distribution of amino acid- and lipid-brevetoxins after intravenous administration to C57BL/6 mice.

    Leighfield, Tod A / Muha, Noah / Ramsdell, John S

    Chemical research in toxicology

    2014  Volume 27, Issue 7, Page(s) 1166–1175

    Abstract: ... Amino acid-brevetoxin conjugates represented by S-desoxy-BTX-B2 (cysteine-BTX-B) and lipid-brevetoxin ... conjugates represented by N-palmitoyl-S-desoxy-BTX-B2 were compared to dihydro-BTX-B. Tissue concentration ... distributed to all tissues, S-desoxy-BTX-B2 concentrated in kidney, and N-palmitoyl-S-desoxy-BTX-B2 having the highest ...

    Abstract Brevetoxins produced during algal blooms of the dinoflagellate Karenia are metabolized by shellfish into reduction, oxidation, and conjugation products. Brevetoxin metabolites comprising amino acid- and lipid conjugates account for a large proportion of the toxicity associated with the consumption of toxic shellfish. However, the disposition of these brevetoxin metabolites has not been established. Using intravenous exposure to C57BL/6 mice, we investigated the disposition in the body of three radiolabeled brevetoxin metabolites. Amino acid-brevetoxin conjugates represented by S-desoxy-BTX-B2 (cysteine-BTX-B) and lipid-brevetoxin conjugates represented by N-palmitoyl-S-desoxy-BTX-B2 were compared to dihydro-BTX-B. Tissue concentration profiles were unique to each of the brevetoxin metabolites tested, with dihydro-BTX-B being widely distributed to all tissues, S-desoxy-BTX-B2 concentrated in kidney, and N-palmitoyl-S-desoxy-BTX-B2 having the highest concentrations in spleen, liver, and lung. Elimination patterns were also unique: dihydro-BTX-B had a greater fecal versus urinary elimination, whereas urine was a more important elimination route for S-desoxy-BTX-B2, and N-palmitoyl-S-desoxy-BTX-B2 persisted in tissues and was eliminated equally in both urine and feces. The structures particular to each brevetoxin metabolite resulting from the reduction, amino acid conjugation, or fatty acid addition of BTX-B were likely responsible for these tissue-specific distributions and unique elimination patterns. These observed differences provide further insight into the contribution each brevetoxin metabolite class has to the observed potencies.
    MeSH term(s) Administration, Intravenous ; Animals ; Brain/metabolism ; Cysteine/chemistry ; Digestive System/metabolism ; Feces/chemistry ; Kidney/metabolism ; Lipids/chemistry ; Lung/metabolism ; Male ; Marine Toxins/blood ; Marine Toxins/chemistry ; Marine Toxins/pharmacokinetics ; Marine Toxins/urine ; Mice, Inbred C57BL ; Muscles/metabolism ; Myocardium/metabolism ; Neurotoxins/blood ; Neurotoxins/chemistry ; Neurotoxins/pharmacokinetics ; Neurotoxins/urine ; Oxocins/blood ; Oxocins/chemistry ; Oxocins/pharmacokinetics ; Oxocins/urine ; Spleen/metabolism ; Testis/metabolism ; Tissue Distribution
    Chemical Substances Lipids ; Marine Toxins ; Neurotoxins ; Oxocins ; brevetoxin (98225-48-0) ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2014-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/tx500053f
    Database MEDical Literature Analysis and Retrieval System OnLINE

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