A case of infantile star anise toxicity.

Chinese star anise (Illicium verum) is a popular herbal remedy for infantile colic. Contamination with a related species of Japanese star anise (Illicium anisatum) has been related to cases of toxicity in infants. We report the case of a 3-month-old infant girl who presented to the emergency department with signs and symptoms of toxicity after recent star anise ingestion. Her presentation is consistent with other reports of toxicity that include particular gastrointestinal and neurological findings. A discussion of the clinical aspects of star anise toxicity, differential diagnosis, and management follows.

Azaspiracid shellfish poisoning: a review on the chemistry, ecology, and toxicology with an emphasis on human health impacts.

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 microg 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.

Neurotoxins from marine dinoflagellates: a brief review.

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.

The first identification of azaspiracids in shellfish from France and Spain.

Incidents of human intoxications throughout Europe, following the consumption of mussels have been attributed to Azaspiracid Poisoning (AZP). Although first discovered in Ireland, the search for the causative toxins, named azaspiracids, in other European countries has now led to the first discovery of these toxins in shellfish from France and Spain. Separation of the toxins, azaspiracid (AZA1) and analogues, AZA2 and AZA3, was achieved using isocratic reversed-phase liquid chromatography coupled, via an electrospray ionisation source, to an ion-trap mass spectrometer. Azaspiracids were identified in mussels (Mytilus galloprovincialis), 0.24 microg/g, from Galicia, Spain, and scallops (Pecten maximus), 0.32 microg/g, from Brittany, France. Toxin profiles were similar to those found in the equivalent shellfish in Ireland in which AZA1 was the predominant toxin.

First evidence of an extensive northern European distribution of azaspiracid poisoning (AZP) toxins in shellfish.

Azaspiracids have recently been identified as the toxins responsible for a series of human intoxications in Europe since 1995, following the consumption of cultured mussels (Mytilus edulis) from the west coast of Ireland. Liquid chromatography-mass spectrometric (LC-MS) methods have been applied in the study reported here to investigate the new human toxic syndrome, azaspiracid poisoning. Separation of azaspiracid (AZA1) and its analogues, 8-methylazaspiracid (AZA2) and 22-demethylazaspiracid (AZA3), was achieved using reversed-phase LC and coupled, via an electrospray ionisation source, to an ion-trap mass spectrometer. These azaspiracids have now been identified in mussels from Craster (north-east England) and Sognefjord (south-west Norway) using source collision induced dissociation-MS and multiple tandem MS detection. AZA1 was the predominant toxin and toxin profiles were similar to those found in contaminated Irish shellfish. This is the first report of the occurrence of these azaspiracids outside Ireland with the significant implications that these toxins may occur in shellfish throughout northern Europe.

Ubiquitous 'benign' alga emerges as the cause of shellfish contamination responsible for the human toxic syndrome, azaspiracid poisoning.

A new human toxic syndrome, azaspiracid poisoning (AZP), was identified following illness from the consumption of contaminated mussels (Mytilus edulis). To discover the aetiology of AZP, sensitive analytical protocols involving liquid chromatography-mass spectrometry (LC-MS) were used to screen marine phytoplankton for azaspiracids. Collections of single species were prepared by manually separating phytoplankton for LC-MS analysis. A dinoflagellate species of the genus, Protoperidinium, has been identified as the progenitor of azaspiracids. Azaspiracid-1, and its analogues, AZA2 and AZA3, were identified in extracts of 200 cells using electrospray multiple tandem MS. This discovery has significant implications for both human health and the aquaculture industry since this phytoplankton genus was previously considered to be toxicologically benign. The average toxin content was 1.8 fmol of total AZA toxins per cell with AZA1 as the predominant toxin, accounting for 82% of the total.

[An epidemic of epileptic seizures after consumption of herbal tea]. / Een epidemie van epileptische aanvallen na drinken van kruidenthee.

UNLABELLED: At the end of September 2001 the Inspectorate for Health Protection and Veterinary Public Health and the National Poisons Control Centre (NPCC) were informed about adverse health effects after consumption of a herbal tea. During consultations it was suggested that Japanese star anise (Illicium anisatum L.), which is known to contain a neurotoxin, may have been inadvertently mixed into the herbal tea. In view of the severity of the adverse health effects and the clear association with consumption of a specific herbal tea, the supplier was urgently advised to withdraw the suspected herbal tea from the market. A total of 63 persons reported symptoms of general malaise, nausea and vomiting 2-4 hours following consumption of the herbal tea. Twenty-two persons required hospitalisation, of whom 16 due to generalised tonic-clonic seizures. Medical investigations revealed no underlying pathology and after supportive treatment, the patients were discharged in good health. Morphologic and organoleptic investigations of the suspected herbal tea indicated that this possibly contained Japanese star anise. NMR analysis of the herbal tea confirmed the presence of the neurotoxin anisatin, a non-competitive GABA-antagonist which can cause hyperactivity of the central nervous system and tonic-clonic seizures. CONCLUSION: Ingestion of a herbal tea containing anisatin caused the reported serious adverse health effects. Close cooperation between clinicians, the Inspectorate for Health Protection and Veterinary Public Health and the NPCC played a vital role in preventing further harm to public health.

[Acute intoxication with fenspiride]. / Ostre zatrucie fenspirydem.

UNLABELLED: According to the best of our knowledge this is the first publication in medical literature about the acute intoxication with fenspiride. The two cases of a young female patients, intoxicated with Eurespal, were described. The orthostatic hypotonia with the blood pressure about 105-115/70 mm Hg in the horizontal position and 70-80/40 mm Hg in the sitting position was dominating. The heart rate was 100-110/min. when lying and 130-140/min. when sitting. The main symptoms were probably caused by inhibition of alpha1 adrenergic receptors. CONCLUSION: Main clinical manifestations make us reconsider the opinion about safety of fenspiride especially after acute intoxication.

Azaspiracid poisoning (AZP) toxins in shellfish: toxicological and health considerations.

It has been almost a decade since a previously unknown human toxic syndrome, azaspiracid poisoning (AZP), emerged as the cause of severe gastrointestinal illness in humans after the consumption of mussels (Mytilus edulis). Structural studies indicated that these toxins, azaspiracids, were of a new unprecedented class containing novel structural features. It is now known that the prevalent azaspiracids in mussels are AZA1, AZA2 and AZA3, which differ from each other in their degree of methylation. Several hydroxylated and carboxylated analogues of the main azaspiracids have also been identified, presumed to be metabolites of the main toxins. Since its first discovery in Irish mussels, the development of facile sensitive and selective LC-MS/MS methods has resulted in the discovery of AZA in other countries and in other species. Mice studies indicate that this toxin class can cause serious tissue injury, especially to the small intestine, and chronic exposure may increase the likelihood of the development of lung tumours. Studies also show that tissue recovery is very slow following exposure. These observations suggest that AZA is more dangerous than the other known classes of shellfish toxins. Consequently, in order to protect human consumers, proper risk assessment and regulatory control of shellfish and other affected species is of the utmost importance.

Comparison of human health risks resulting from exposure to fungicides and mycotoxins via food.

The interest in holistic considerations in the area of food safety is increasing. Risk managers may face the problem that reducing the risk of one compound may increase the risk of another compound. An example is the potential increase in mycotoxin levels due to a reduced use of fungicides in crop production. The Integrated Probabilistic Risk Assessment (IPRA) model was used to compare the estimated health impacts on humans caused by crops contaminated with the fungicides spiroxamine (SPI) and tebuconazole (TEB) or with the mycotoxins deoxynivalenol (DON) and zearalenone (ZEA). The IPRA model integrates a distribution characterising the exposure of individuals with a distribution characterising the susceptibility of individuals towards toxic effects. Its outcome, a distribution of Individual Margins of Exposure (IMoE), served as basis to perform comparisons of compounds, effects, countries, and population groups. Based on the available data and the assumptions made, none of the four compounds was found to have impact on human health in the addressed scenarios. The IMoE distributions were located as follows: DON

Marine toxins and the cytoskeleton: azaspiracids.

The azaspiracids (AZAs) are a group of marine phycotoxins discovered during the second half of the 1990s. Several cases of human intoxication due to the presence of AZAs in shellfish have been reported, with gastrointestinal symptoms. Toxicological studies in vivo and in vitro have revealed that various cell types are sensitive to AZA toxicity; however, the biological target of the toxin is still unknown. One of the in vitro signs of AZA toxicity is the alteration of the actin cytoskeleton arrangement, which is accompanied by changes in cell shape and loss of cell adherence to the substrate. Moreover, the cytoskeletal damage is irreversible after toxin withdrawal. Several other in vitro effects of AZAs have been described that could be related to cytoskeletal changes, such as E-cadherin degradation, caspase activation/apoptosis, membrane cholesterol reduction, or gene expression alterations, although evidence for a direct relationship between any of these effects and AZA-induced cytoskeletal damage is still nonexistent.

A sensitive and specific determination method for azaspiracids by liquid chromatography mass spectrometry.

A liquid chromatography/mass spectrometry (LC/MS) method was developed for the sensitive and specific determination of azaspiracid and its two analogs, the causative toxins of azaspiracid poisoning that occurred in the Netherlands and Ireland. The LC/MS method provided a detection limit of 50 pg for azaspiracid. The sensitivity was approximately 8 x 10(4) times greater than the mouse bioassay. The method was used to confirm the presence of azaspiracids in toxic mussels collected at Arranmore Island, Ireland in 1997.

Azaspiracid poisoning, the food-borne illness associated with shellfish consumption.

Azaspiracid poisoning (AZP) is a recently discovered toxic syndrome that was identified following severe gastrointestinal illness from the consumption of contaminated mussels (Mytilus edulis). The implicated toxins, azaspiracids, are polyethers with unprecedented structural features. Studies toward total toxin synthesis revealed that the initial published structures were incorrect and they have now been revised. These toxins accumulate in bivalve molluscs that feed on toxic microalgae of the genus Protoperidinium, previously considered to be toxicologically benign. Although first identified in shellfish from Ireland, azaspiracid contamination of several types of bivalve shellfish species has now been confirmed throughout the western coastline of Europe. Toxicological studies have indicated that azaspiracids can induce widespread organ damage in mice and that they are probably more dangerous than previously known classes of shellfish toxins. The exclusive reliance on live animal bioassays to monitor azaspiracids in shellfish failed to prevent human intoxications. This was a consequence of poor sensitivity of the assay and the fact that azaspiracids are not exclusively found in the shellfish digestive glands used for toxin testing. The strict regulatory control of azaspiracids in shellfish now requires frequent testing of shellfish using highly specific and sensitive methods involving liquid chromatography-mass spectrometry.