Methylenecyclopropylglycine and hypoglycin A intoxication in three Pére David's Deers (Elaphurus davidianus) with atypical myopathy.

BACKGROUND: Hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG) from seeds/seedlings of Sycamore maple (SM, Acer pseudoplatanus) causes atypical myopathy (AM) in horses. AM was not known to occur in wild ruminants until several fatalities in milus (Elaphurus davidianus) following the ingestion of HGA in SM seeds. However, a role for MCPrG has not previously been evaluated. OBJECTIVES: To test the hypothesis that MCPrG is also a major factor in AM in milus, three milus (M1, M2, M3) from the Zoo Dresden (aged 7-11 years, 2 females and 1 male, in good nutritional condition) that developed AM were studied. METHODS: Serum, urine and methanol extracts from the liver, kidney, rumen digesta and faeces were analysed by ultrahigh-performance liquid chromatography-tandem mass spectrometry for HGA, MCPrG and for conjugates of carnitine (C) and glycine (G): Methylenecyclopropylacetyl (MCPA)-G, MCPA-C, Methylenecyclopropylformyl (MCPF)-G, MCPF-C, butyryl-C and isobutyryl-C. RESULTS: HGA in serum was high (M2 480 nmol/L; M3 460 nmol/L), but MCPrG was not. HGA and MCPrG were found in rumen and faeces extracts, and MCPrG was also identified in the liver. Metabolites of HGA and MCPrG were high in serum, urine and liver, but not in the rumen or faeces. CONCLUSIONS: This study shows that MCPrG is involved in the pathophysiology of AM in milus. The metabolism of MCPrG is considered to be faster because, after ingestion, the specific metabolites appear highly concentrated in the serum. The high toxin concentration in the liver suggests that a possible transfer into products for human consumption may pose a risk.

Cardiotoxicity and serotonin syndrome complicating a milnacipran overdose.

Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor, recently approved for use in the USA for treatment of fibromyalgia. This case report describes a 59-year-old woman who ingested 3,000 mg of milnacipran in a suicide attempt. Following the ingestion, she became obtunded and developed autonomic instability. She required mechanical ventilation, treatment for hypertension, and then ultimately vasopressor support for refractory hypotension. In addition, she developed a transient, acute cardiac dysfunction with global hypokinesis and an ejection fraction of 30%. Resolution of the cardiac dysfunction was documented on repeat echocardiogram 2 days after the initial study. This was confirmed by cardiac catheterization performed 4 days after the acute ingestion in which coronary arteriogram was normal and left ventricular ejection fraction was 70%. Acute overdose was confirmed by quantification of plasma milnacipran concentration of 8,400 ng/mL obtained 5 h post-ingestion. To our knowledge, this represents the first case of cardiac toxicity complicating a milnacipran overdose in the medical literature.

Fatal intoxication with milnacipran.

The antidepressant milnacipran is a double serotonin/noradrenalin reuptake inhibitor. The low reported incidence of intoxication indicates excellent tolerance in comparison with tricyclic and second generation antidepressants. We report a fatal intoxication associating milnacipran, at blood levels (femoral=21.5 mg/l, cardiac=20 mg/l) 40-fold higher than the usual treatment concentration, and six other molecules (fluoxetine, norfluoxetine, sertraline, cyamemazine, nordazepam and oxazepam) at therapeutic levels. To the best of our knowledge, this is the first reported fatal intoxication involving milnacipran.

Effect of Cry3Bb transgenic corn and tefluthrin on the soil microbial community: biomass, activity, and diversity.

Transgenic Bt corn expressing the Cry3Bb insecticidal protein active against corn rootworm (CRW) (Diabrotica spp.; Coleoptera: Chrysomelidae) was released for commercial use in 2003 and is expected to be widely adopted. Yet, the direct and indirect risks to soil microorganisms of growing this CRW-resistant Bt corn versus applying insecticides to control the rootworm have not been assessed under field conditions. The effects of CRW Bt corn and the insecticide tefluthrin [2,3,5,6-tetrafluoro-4-methylbenzyl (Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate] on soil microbial biomass, activity (N mineralization potential, short-term nitrification rate, and soil respiration), and bacterial community structure as determined by terminal restriction fragment length polymorphism (T-RFLP) analysis were assessed over two seasons in a field experiment. Bt corn had no deleterious effects on microbial activity or bacterial community measures compared with the non-transgenic isoline. The T-RFLP analysis indicated that amplifiable bacterial species composition and relative abundance differed substantially between years, but did not differ between rhizosphere and bulk soils. The application of tefluthrin also had no effect on any microbial measure except decreased soil respiration observed in tefluthrin-treated plots compared with Bt and non-transgenic isoline (NoBt) plots in 2002. Our results indicate that the release of CRW Bt corn poses little threat to the ecology of the soil microbial community based on parameters measured in this study.

Sudden death by inhalation of cyclopropane.

This paper reports the case of a 22-year-old white male who was found dead in a storage room as a result of a fatal ingestion of cyclopropane. Cyclopropane is a sweet-smelling, irritating gas. Autopsy findings revealed congestion and hemorrhagic edema of the lungs, congestion of the trachea, and early autolysis. Cyclopropane was determined by headspace gas chromatography and mass spectrometry. To our knowledge, this is the first reported fatality involving cyclopropane.

Commentary on a review on the mechanism of ackee-induced vomiting sckness

A recent article concluded that glutamic acid probably plays a central role in the vomiting and neurological features of ackee poisoning. The present article draws attention to misconceptions in the basis of that hypothesis, and reviews important evidence supporting a different view

Commentary on a review on the mechanism of Ackee-induced vomiting sickness

A recent review article concluded that glutamic acid probable plays a central role in the vomiting and neurological features of ackee poisoning. The present article draws attention to misconceptions in the basis of that hypothesis, and reviews important evidence suppporting a different role (AU)

Effects of ackee fruit extracts on bronchomotor tone in rats

The unripe ackee fruit, when eaten, is known to cause serious clincial manifestations, including vomitting, hypoglycaemia and acidosis. The effects, of various extracts from the arilli of the unripe ackee fruit (including hypoglycin-A) on the lungs from rats were examined in an in vitro preparation. All the extracts were found to induce moderately severe broncho-constriction, indicating a possible contribution of these effects to the observed toxicity of ackee

Effects of ackee fruit extracts on bronchomotor tone in rats

The unripe ackee fruit, when eaten, is known to cause serious clinical manifestations, including vomiting, hypoglycaemia and acidosis. The effects, of various extracts from the arilli of the unripe fruit (including hypoglyin-A) on the lungs from rats were examined in an in vitro preparation. All the extracts were found to induce moderately severe broncho-constriction, indicating a possible contribution of these effects to the observed toxicity of ackee (AU)

A re-examination of the mechanism of ackee-induced vomiting sckness

The hypoglycemia seen in ackee poisoning almost certainly results from the presence of hypoglycin A in the aril. However, the mechanisms underlying the vomiting and neurological disrders have not been properly established. We have, in thes review, re-examined the latter and proposed that the vomiting of glutamic and neurological feactures of ackee poisoning probably result from the excitotoxic properties of glutamic and aspartic acids derived directly and indirectly from ackee intake

Organic aciduria in rats made resistant to hypoglycin toxicity by pretreatment with clofibrate.

1. The lethal, hypoglycaemic and hypothermic effects of hypoglycin in fasted rats are prevented if the rats had been fed on a diet containing clofibrate (0.5% w/w). 2. Injection of hypoglycin into fasted rats maintained on a standard diet caused severe prostration, hypothermia and a massive dicarboxylic aciduria [Tanaka (1972) J. Biol. Chem. 247, 7465-7478]. 3. Rats maintained on a diet containing clofibrate appeared normal after injection of hypoglycin, but had a marked dicarboxylic aciduria which was less than that induced in rats on a normal diet. 4. After administration of hypoglycin, butyryl-CoA and decanoyl-CoA, but not palmitoyl-CoA, dehydrogenase activities were strongly inhibited (80-95%) in the livers of animals on a standard diet. 5. Clofibrate feeding decreased the inhibition of these dehydrogenases to about 40-60%. 6. It was concluded that although clofibrate protects against the toxic effects of hypoglycin, some enzyme inhibitions as indicated by dicarboxylic aciduria are only partly prevented.