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ABSTRACT: Neurotoxins cause biochemical and molecular events which indicate early stage effects in exposed persons well before or well below the induction of overt disease. Monitoring these early events may represent a valid approach to developing markers of neurotoxicity in individuals exposed to environmental chemicals. In neurotoxicology, the use of biochemical markers is more problematic compared to other fields due to the complexity of central nervous system function, the multistage nature of neurotoxic events, and the inaccessibility of target tissue. Nevertheless, new biochemical assays have been developed in recent years to assess exposure, subclinical effects, and susceptibility to neurotoxic disorders. This paper reviews novel biomarkers of neurotoxicity and discusses perspectives and limitations of their use in occupational and environmental medicine.
Environmental Research 02/2001; 85(1):31-6. · 3.40 Impact Factor
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ABSTRACT: Ciguatera poisoning causes mainly gastrointestinal and neurological effects of variable severity. However, symptoms of peripheral neuropathy with paresthesias and paradoxical disturbance of thermal sensation are the hallmark. Electrophysiological studies are often normal, except in severe cases. We report four people who developed mild ciguatera poisoning after barracuda ingestion. Electrophysiological studies documented normocalcemic latent tetany. These findings are consistent with ciguatoxin's mechanism of toxicity, which involves inactivation of voltage-gated Na(+) channels and eventually increases nerve membrane excitability.
Muscle & Nerve 11/2000; 23(10):1598-603. · 2.37 Impact Factor
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ABSTRACT: Methylmercury (MeHg) affects several parameters of cholinergic function. These alterations are thought to play a role in MeHg neurotoxicity. In vitro experiments have indicated that MeHg acts as a strong competitive inhibitor of radioligand binding to muscarinic cholinergic receptors (mAChRs) in rat brain. Furthermore, rat brain mAChRs share several pharmacologic characteristics of similar receptors present on lymphocytes. Using the muscarinic antagonist [(3)H]quinuclidinyl benzilate (QNB) to label receptors, we investigated the in vivo interactions of MeHg with rat brain mAChRs. We also investigated whether MeHg-induced central mAChR changes are reflected by similar alterations in splenic lymphocytes. Exposure to low doses of MeHg--0.5 or 2 mg/kg/day in drinking water--for 16 days significantly increased (20-44% of control) mAChRs density (B(max)) in the hippocampus and cerebellum without affecting receptor affinity (K(d)). The effect of MeHg did not occur immediately; it was not apparent until 2 weeks after the termination of treatment. No significant changes in [(3)H]QNB binding were observed in the cerebral cortex. In splenic lymphocytes, mAChR density was remarkably increased (95-198% of control) by day 14 of MeHg exposure and remained enhanced 14 days after the cessation of treatment. These results suggest up-regulation of mAChRs in selected brain regions (hippocampus and cerebellum) after prolonged low-level ingestion of MeHg in rats. These cerebral effects are delayed in onset and are preceded by a marked increase in density of mAChRs on lymphocytes. In chronic MeHg exposure, peripheral lymphocytes may represent a sensitive target for the interaction of MeHg with mAChRs and, therefore, may be predictive indicators of later adaptive response involving cerebral mAChRs. Additionally, the effect of MeHg on lymphocyte mAChRs in vivo indicates that this receptor system should be investigated further as a possible target for MeHg immunotoxicity.
Environmental Health Perspectives 02/2000; 108(1):29-33. · 7.04 Impact Factor
