Poisoning due to tutin in honey-a report of an outbreak in New Zealand.

AIM: In autumn 2008, an outbreak of toxic honey poisoning was identified. The outbreak was not recognised initially until three cases from one family group presented to hospital, with a common factor of recent consumption of locally produced honey. The aim of this study was to investigate potential cases of this honey poisoning and determine which toxin was involved. METHOD: The incident was investigated retrospectively by Waikato District Health Board's Population Health unit and the New Zealand Food Safety Authority (NZFSA). Identified patients were followed up by questionnaire to gather case information. HortResearch (now Plant and Food Research) tested honey samples for toxins. RESULTS: The causative agent was identified as tutin, which comes from the New Zealand native plant tutu (Coriaria arborea) which has long been known as a potential source of contamination of honey produced in the warmer parts of New Zealand. Retrospective case investigation identified a total of 22 possible or probable cases, based on a clinical case definition. The spectrum of toxic effects reported were broadly similar to those previously described for tutin, derived either directly from the plant itself or indirectly from honey. There were 13 samples of honey, linked to symptomatic individuals, which were available for testing. Of these, 10 were positive for tutin and its hydroxy metabolite hyenanchin (hydroxytutin) and one was positive for hyenanchin alone. CONCLUSION: Toxic honey production is a significant risk in parts of New Zealand. Beekeepers and health professionals need to be informed of this risk and know how best to manage it. Due to this poisoning incident, public and professional awareness of honey poisoning has been substantially enhanced. This incident led to development of new food safety standards for New Zealand honey.

Dictyoceratidan poisons: Defined mark on microtubule-tubulin dynamics.

Tubulin/microtubule assembly and disassembly is characterized as one of the chief processes during cell growth and division. Hence drugs those perturb these process are considered to be effective in killing fast multiplying cancer cells. There is a collection of natural compounds which disturb microtubule/tubulin dis/assemblage and there have been a lot of efforts concerted in the marine realm too, to surveying such killer molecules. Close to half the natural compounds shooting out from marine invertebrates are generally with no traceable definite mechanisms of action though may be tough anti-cancerous hits at nanogram levels, hence fatefully those discoveries conclude therein without a capacity of translation from laboratory to pharmacy. Astoundingly at least 50% of natural compounds which have definite mechanisms of action causing disorders in tubulin/microtubule kinetics have an isolation history from sponges belonging to the Phylum: Porifera. Poriferans have always been a wonder worker to treat cancers with a choice of, yet precise targets on cancerous tissues. There is a specific order: Dictyoceratida within this Phylum which has contributed to yielding at least 50% of effective compounds possessing this unique mechanism of action mentioned above. However, not much notice is driven to Dictyoceratidans alongside the order: Demospongiae thus dictating the need to know its select microtubule/tubulin irritants since the unearthing of avarol in the year 1974 till date. Hence this review selectively pinpoints all the compounds, noteworthy derivatives and analogs stemming from order: Dictyoceratida focusing on the past, present and future.

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.

Norsesquiterpene glycosides in bracken ferns (Pteridium esculentum and Pteridium aquilinum subsp. wightianum) from Eastern Australia: reassessed poisoning risk to animals.

Austral bracken Pteridium esculentum contains three unstable norsesquiterpene glycosides: ptaquiloside, ptesculentoside, and caudatoside, in variable proportions. The concentration of each of the glycosides was determined in this study as their respective degradation products, pterosin B, pterosin G and pterosin A, by HPLC-UV analysis. Samples of P. esculentum collected from six sites in eastern Australia contained up to 17 mg of total glycoside/g DW, with both ptaquiloside and ptesculentoside present as major components accompanied by smaller amounts of caudatoside. Ratios of ptaquiloside to ptesculentoside varied from 1:3 to 4:3, but in all Australian samples ptesculentoside was a significant component. This profile differed substantially from that of P. esculentum from New Zealand, which contained only small amounts of both ptesculentoside and caudatoside, with ptaquiloside as the dominant component. A similar profile with ptaquiloside as the dominant glycoside was obtained for Pteridium aquilinum subsp. wightianum (previously P. revolutum ) from northern Queensland and also P. aquilinum from European sources. Ptesculentoside has chemical reactivity similar to that of ptaquiloside and presumably biological activity similar to that of this potent carcinogen. The presence of this additional reactive glycoside in Australian P. esculentum implies greater toxicity for consuming animals than previously estimated from ptaquiloside content alone.

[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.

Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss.

BACKGROUND: Herbs from Lycopodium are generally reputed to be nontoxic and are occasionally used for preparing a salubrious tea. In Europe, the common Lycopodium clavatum can be easily confused with Lycopodium selago, the fir club moss. CASE REPORT: We report 2 patients who drank a tea, erroneously prepared from dried herbs of Lycopodium selago, which resulted in sweating, vomiting, diarrhea, dizziness, cramps, and slurred speech. These symptoms were suggestive of a cholinergic mechanism. To elucidate the active principle, aqueous extracts of Lycopodium selago were checked for their suspected anticholinesterase activity using human erythrocytes as an enzyme source in a modified Ellman assay. The extracts did exhibit significant anticholinesterase activity. The anticholinesterase(s) were most effectively extracted with dichloromethane and isolated by high-performance liquid chromatography. The major compound with anticholinesterase activity co-chromatographed with authentic huperzine A, but had a 2-3-fold higher inhibitory potency than the racemic standard. The amount of huperzine A found in the Lycopodium selago sample used for the tea preparation was calculated to be sufficient for a relevant acetylcholinesterase inhibition. CONCLUSION: The signs and symptoms of Lycopodium selago poisoning are consistent with the anticholinesterase activity of huperzine A and should favorably respond to atropine therapy. This report demonstrates once more that laymen should not be encouraged to gather their remedies from "Mother Nature" without advanced botanical knowledge.

Status spongiosis, optic neuropathy, and retinal degeneration in Helichrysum argyrosphaerum poisoning in sheep and a goat.

Lesions of natural Helichrysum argyrosphaerum poisoning were studied in eight sheep and one goat. Light microscopic examination revealed widespread, bilaterally symmetrical status spongiosis of the white matter of the brain consistently present in the subependymal area adjacent to the lateral ventricles, cerebellar peduncles, and brain stem in all animals. In three animals, the ultrastructural finding of intramyelinic vacuolation due to splitting of the myelin lamellae at the intraperiod lines indicated myelin edema. There was also mild distension of perivascular and extracellular spaces in the severely affected areas. Significant changes were absent in neurons, glial cells, axons, or blood vessel walls. Myelin edema associated with degeneration and loss of axons and myelin and astrocytic gliosis was present in the intraorbital and intracranial portions of the optic nerves. In the intracanalicular portions of the nerves in three animals that were studied, more chronic lesions consisting of fibrosis and atrophy of the nerve suggested that the optic neuropathy follows compression of the nerve in the optic canal as a result of myelin edema. The toxic principle of the plant also caused a degenerative retinopathy in five animals. The essential histopathologic change was degeneration and loss of the photoreceptor outer segments predominantly in the nontapetal retina. These retinal lesions were associated with hyperplasia and hypertrophy and with migration of the pigmented epithelium, focal retinal separation, and depletion and loss of the nuclear layers.

Parthenium weed and human health in Queensland.

Allergic reactions to the pollen and plant dust of parthenium weed are causing major health problems in central Queensland, which can be expected to increase, especially as the pasture weed is rapidly spreading south. This paper reviews published information on health aspects of this weed and calls attention to its spread into areas with much greater population.

The effect of dietary supplements on chronic bitterweed (Hymenoxys odorata) poisoning in sheep.

Two experiments were designed to establish a chronic bitterweed dose in sheep and to study the prevention of chronic bitterweed poisoning with dietary supplements of high protein (20% crude protein) and sodium sulfate. The first experiment consisted of 5 lambs in each of 3 groups. The low dose received up to 5.0 g bitterweed/kg/day which was equivalent to 10 mg hymenoxon/kg bw. The high dose group received a maximum bitterweed dose of 1 g/kg/day or 20 mg hymenoxon/kg. The final average weights of the low (29 kg) and the high (30 kg) dose groups were significantly different from the control (40 kg) group. The prophylactic experiment consisted of 5 groups of 4 sheep each. Each group received a different combination of bitterweed, a basal ration, soybean meal, urea, or sodium sulfate. The soybean meal and urea were used to adjust the ration to 20% crude protein, and each animal received 1.2 g bitterweed/kg/day. The high protein-sodium sulfate diet did not prevent chronic bitterweed toxicity, but soybean meal-sodium sulfate combination had the greatest effect on the reduction of bitterweed toxicity. Urea potentiated the toxic effects of bitterweed.

The use of trichothecene-contaminated grains in feeds.

A review is presented describing the relative efficiencies of the various technologies that have been proposed to permit incorporation of mycotoxin-contaminated grains into animal diets without adversely influencing growth rate or resulting in hazardous residues in edible animal tissues. When the degree of contamination is modest, it may be possible to dilute the contaminated materials with uncontaminated grain to lower the concentration of trichothecenes below the threshold of significant biological activity. A less useful alternative to dilution is the other mechanical approach of milling to remove the most heavily contaminated fractions of the grain. Chemical destruction of triochothecenes is also a possibility. An example is the use of sodium bisulfite treatment to destroy deoxynivalenol in contaminated corn. Such treatments may, however, reduce palatability and nutritional value. When the biochemical mechanism of trichothecene toxicity is known, in vivo therapeutic treatments may be possible. It has been shown, for example, that T-2 toxin-induced changes in brain prostaglandin production can be overcome by treatment with dexamethasone resulting in increased survival. A similar effect was seen using the selective platelet activating factor antagonist BN 52021. Another approach is the use of dietary treatments to either promote in vivo detoxification of mycotoxins or to reduce absorption from the digestive tract with the aid of nonnutritive binding agents.

Outbreak of trichothecene mycotoxicosis associated with consumption of mould-damaged wheat production in Kashmir Valley, India.

During June to September, 1987, there were reports that a considerable segment of the population of Kashmir Valley, India, were affected by a gastrointestinal disorder. Epidemiological investigations and laboratory based studies indicated that the outbreak was associated with the consumption of bread made from mould-damaged wheat. The disease was not age or sex specific. Evidence of mould damage of wheat consisted of the presence of moulds (such as Fusarium sp, Aspergillus sp), and varying quantities of trichothecene mycotoxins (such as deoxynivalenol, nivalenol, acetyldeoxynivalenol, T-2 toxin) in samples tested. The symptoms were reproduced in dogs fed extracts of contaminated samples. The finding that trichothecene mycotoxins, especially deoxynivalenol trichothecene, cause symptoms in man emphasizes the need for a reappraisal of its safety limits in food.

Fusarium mycotoxins from peanuts suspected as a cause of sandhill crane mortality.

An estimated 9,500 sandhill cranes (Grus canadensis) died in Gaines County, Texas and Roosevelt County, New Mexico between 1982 and 1987. The predominant clinical sign observed in sick cranes was their inability to hold their heads erect, both while standing and flying. Multiple muscle hemorrhages and submandibular edema were the most common lesions seen at necropsy. Mycotoxins produced by Fusarium sp. growing during cold, wet weather on peanuts left in the field after harvest, the predominant foods of the dead cranes at the time of these mortality events, were identified as the most likely cause of this mortality. Rendering moldy peanuts inaccessible to the cranes by conventional tillage resulted in reduced crane mortality in these areas.

Potential for dietary amino acid precursors of neurotransmitters to overcome neurochemical changes in acute T-2 toxicosis in rats.

Experiments were conducted to determine the potential for overcoming T-2 toxin-induced changes in brain neurotransmitter concentrations through dietary manipulation. Rats were fed either a tryptophan-deficient, gelatin-based diet or the same diet supplemented with a mixture of large neutral amino acids for 4 d. Rats were then dosed with 0 or 2.0 mg T-2 toxin/kg body weight and killed 4, 8 or 12 h after dosing. The large neutral amino acid supplements successfully reduced brain concentrations of tryptophan and serotonin in control rats, but this was not enough to overcome the acute effects seen in T-2 toxin-treated rats. A further experiment was then conducted to monitor the effect of T-2 toxin on the ratio of free to protein-bound tryptophan in plasma. Total plasma tryptophan increased in T-2 toxin-treated rats, although there were no significant differences in the ratio of free to protein-bound tryptophan. A final experiment was conducted to determine the specificity of the T-2 toxin effect on concentrations of plasma amino acids. Concentrations of amino acids that use the large neutral amino acid transport system into the brain were higher in T-2 toxin-treated animals. The only other amino acid that had a higher concentration was arginine. It was concluded that acute doses of T-2 toxin may selectively alter membrane transport of amino acids.

[Enzyme parameters in the evaluation of the combined effects of protein deficiency and T-2 mycotoxin]. / Enzimologicheskie pokazateli pri otsenke kombinirovannogo vozdeistviia belkovoi nedostatochnosti i T-2 mikotoksina.

Male Wistar rats received a low-protein (4.5% protein) diet during 30 days, and T-2-toxin was administered to them through a gastric tube, in a dose of 0.54 mg/kg, during 15 days. The results obtained showed activation of hepatic lysosomal enzymes (sulfatase A and B aryl and beta-glucosidase) and alkaline phosphatase, and to an essential suppression of enzymatic activity of peroxisomes - catalase, glycolate oxidase and D-amino acid oxidase. A sharp aggravation of the intoxication symptoms and pronounced intensification of changes in enzymatic activity in the liver, spleen, thymus and blood serum were recorded in the animals given T-2 toxin simultaneously with the low-protein diet.

Assessment of a general therapeutic protocol for the treatment of acute T-2 toxicosis in swine.

T-2 toxin, a trichothecene mycotoxin suspected of being used as a chemical warfare agent, was administered iv to swine at a dose of 3.6 mg/kg body weight (iv LD50 approximately 1.2 mg/kg). Four different therapeutic protocols were assessed for their efficacy in the treatment of the resultant acute T-2 toxicosis syndrome. One therapeutic protocol included the combined use of metoclopramide, activated charcoal, magnesium sulfate, dexamethasone sodium phosphate, sodium bicarbonate and normal saline. The other 3 protocols utilized the same agents less 1 of the following: the combination of activated charcoal and magnesium sulfate, sodium bicarbonate, or normal saline. All 4 treatment groups showed improved survival times compared to a positive T-2 control group. Within the limits of the study, it would appear that the removal of activated charcoal and magnesium sulfate was most detrimental to the T-2 toxin-dosed swine.

Changes in circulatory white blood cells of mice and rats due to acute trichothecene intoxication.

In mice, administration of pure T-2 toxin caused a rapid decrease of lymphocyte counts, which was linear with respect to dose, whereas granulocyte counts showed a delayed decrease. The blood cell counts of both cell types attained normal values after 4-7 days. Similar results were obtained for crude A-, B- and macrocyclic type trichothecene. Intoxication of rats with T-2 toxin or crude A-type trichothecene caused changes in white blood cells, which differed quantitatively from those in the mouse: lymphocyte counts decreased less and a rapid transient increase of granulocytes was more obvious. Results of this study show that lymphocyte and granulocyte blood cell counts of small rodents respond sensitively to acute intoxication with various trichothecenes.

[Hepatocyte ultrastructure in mice with chronic T-2 mycotoxicosis]. / Ul'trastruktura gepatotsitov myshei pri khronicheskom mikotoksikoze T-2.

Trichothecene mycotoxin (T-2 toxin) was administered by gastric intubation to CBAXC57BL/6 mice at a dose of 0.33-0.45 mg/kg for 6 months. No symptoms of intoxication were observed, however, electron microscopic studies revealed a severe damage of hepatocyte structure, especially of smooth and rough endoplasmic reticulum. Besides the destruction of hepatocytes an increase in the number of primary and secondary lysosomes was observed. Regenerating foci were found in the majority of liver cells. In chronic T-2 mycotoxicosis there is a strong correlation between the damage of hepatocyte ultrastructure and the changes in organella-specific enzymatic activity in the liver, that was described previously.