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J Truelove

Publications and source records attributed to J Truelove.

9 recordsLinked to original sources
PubMed1990

Experimental oral toxicity of domoic acid in cynomolgus monkeys (Macaca fascicularis) and rats. Preliminary investigations.

A recent outbreak of marine food poisoning in humans was attributed to the consumption of blue mussels (Mytilus edulis L.) contaminated with domoic acid (DA) that was produced by the diatom Nitzschia pungens. The clinical and morphological effects of single oral doses of extracts of mussels contaminated with DA or of DA isolated from toxic mussels were investigated in small groups (one to six) of cynomolgus monkeys (Macaca fascicularis; 0.5-10 mg DA/kg body weight) and of Sprague-Dawley rats (60 to 80 mg DA/kg body weight). Control animals were either given saline or were not treated. To test whether monosodium glutamate, present in the food consumed by some affected humans, and dimethylsulphoxide, suspected of being present in the plankton, enhanced the response, monosodium glutamate (at 0.25% of mussel extract bolus) or dimethylsulphoxide (at 1 g per bolus) were co-administered to two (one each) of the DA-treated monkeys. DA-treated monkeys developed transient excitation characterized by vomiting. DA-treated rats showed withdrawal followed by hyperexcitation and death (in one case). Mild to moderate central nervous system lesions consistent with neuroexcitation were present in both monkeys and rats. The addition of monosodium glutamate and dimethylsulphoxide had no significant effect on the appearance and severity of central nervous system clinical signs and lesions. The wide variations in the response of test animals to orally administered DA were attributed to the protective effect of vomiting, and to suspected incomplete or slow gastro-intestinal absorption of the toxic agent. The results reinforce the view that DA is an emetic and that under appropriate conditions may also inflict excitotoxic central nervous system damage.

Administration, Oral↗
PubMed1990

Acute neurotoxicity of domoic acid in the rat.

A recent outbreak of human food poisoning, characterized by severe gastrointestinal and neurologic abnormalities, with a fatal outcome in 3 patients, was attributed to the consumption of poisonous mussels containing domoic acid at an abnormally high concentration. The purpose of the present study was to determine if domoic acid, a glutamate analogue extracted from poisonous mussel, was neurotoxic to rats. Groups of female Sprague-Dawley rats were dosed once intraperitoneally with 0, 1, 2, 4, or 7.5 mg domoic acid/kg of body weight and observed for a maximum period of 24 hr. Clinically, control rats and rats in the 1 mg/kg group were unremarkable. Seventy-five percent of the animals in the 2 mg/kg group had equivocal transient behavioral signs. One that was given 2 mg/kg and all rats given in excess of 4 mg/kg of body weight developed unequivocal behavioral and neurologic signs culminating in partial seizures and status epilepticus. Histopathologically, severely affected rats developed selective encephalopathy characterized by neuronal degeneration and vacuolation of the neuropil in the limbic and the olfactory systems, and retinopathy characterized by neuronal hydropic degeneration of the inner nuclear layer and vacuolation of the external plexiform layer. The results of this study suggest that domoic acid is excitotoxic and causes a characteristic syndrome with clinical signs and histopathologic lesions similar to those reported for kainic acid.

Animals↗
PubMed1990

Acute parenteral neurotoxicity of domoic acid in cynomolgus monkeys (M. fascicularis)

To study the CNS effects of domoic acid (D.A.), 6 adult Cynomolgus monkeys (M. fascicularis) were dosed intraperitoneally (4 mg/kg) or intravenously (0.025-0.5 mg/kg) with D.A. obtained from cultured mussels contaminated with this neurotoxin. Clinical signs of neurotoxicity were preceded by a short presymptomatic period (2-3 min) and an even shorter prodromal period (0.5-1 min). The symptomatic period proper was characterized by persistent chewing with frothing, varying degrees of gagging, and vomit. Monkeys in the higher dose regimen exhibited additional signs including abnormal head and body positions, rigidity of movements and loss of balance, and tremors. The duration of the symptomatic period was dose dependent. Excitotoxic lesions consisting of vacuolation of the neuropil, astrocytic swelling, and neuronal shrinkage and hyperchromasia were detected in the area postrema, the hypothalamus, the hippocampus, and the inner layers of the retina in monkeys given D.A. at 0.5 mg/kg intravenously and 4 mg/kg intraperitoneally. It was concluded that D.A., administered intravenously, is neuroexcitatory and a powerful emetic at doses of 0.025 to 0.2 mg/kg. At higher doses (0.5 mg/kg intravenously and 4 mg/kg intraperitoneally), D.A. is strongly excitotoxic.

Animals↗
PubMed1979

Effect of hydroxyl group substituents on pyran ring on hydrolysis rate of benzoates: 2-tetrahydropyranyl benzoate.

The hydrolysis of 2-tetrahydropyranyl benzoate was followed spectrophotometrically at 240 nm and was first order with respect to the compound, independent of pH, and very sensitivie to solvent polarity and had an isotope effect (kD2O/kH2O) near unity. The pH-independent hydrolysis rate was about 1 X 10(6) times faster than that of the corresponding glucosly benzoate. The results suggest that the presence of hydroxyl groups on the pyran ring has tremendous effect on the hydrolysis rate of these compounds.

Benzoates↗
PubMed1979

Kinetics and mechanism of hydrolysis of 1-(2'-acetoxybenzoyl)-2-deoxy-alpha-D-glucopyranose, a novel aspirin prodrug.

The formation rate of aspirin from the prodrug was determined as a function of the pH, temperature, and dielectric constant of the solvent spectrophotometrically and was confirmed by high-pressure liquid chromatography. Aspirin formation was first order with respect to the prodrug and zero order with respect to the hydroxide-ion concentrations. The hydrolysis rate was independent of buffer concentration but very sensitive to the dielectric constant of the solvents. The half-life for the formation of aspirin at 37 degrees was 7 min. The activation energy for the hydrolysis was 23.7 kcal/mole. The results suggest that the hydrolysis of the prodrug to aspirin proceeds by an SN1-type mechanism.

Aspirin↗