To assess the signs and symptoms of acute valproic acid (VPA) overdose in young children. Methods:The medical records of previously healthy children admitted to the pediatric department for accidental acute VPA poisoning during the years 1995-1999 were evaluated retrospectively. Information was retrieved on serum VPA concentrations, signs and symptoms on admission and during hospitalization, electrocardiography findings, and laboratory tests.Results: All 16 children included in the study were in the age range of two to six years. In 13 cases, the drug had been intended for use by a family member and was ingested accidentally by the child. Three children were receiving VPA to treat a seizure disorder and had an adverse reaction due to unintentional overdose. For four children, a diagnosis of VPA poisoning was not made on admission because of inadequate history and was revealed only on toxicology screening. Drowsiness occurred in all the children, hypotonia in 11, ataxia in eight, miosis in six, and mild hypernatremia in five. Only two children had mildly elevated hepatic enzymes. The peak VPA serum concentrations in the study group ranged from 128 to 142 pg/mL (mean ± SD 135 ± 4.25; therapeutic range 50-100).Conclusions: Drowsiness was the most common symptom in young children with mild to moderate VPA poisoning. Other symptoms included hypotonia, ataxia, and miosis. A third of the patients had hypernatremia, most probably due to VPA formulated as sodium valproate. Unlike in cases of chronic toxicity, hepatic damage was not a characteristic finding.

Data suggesting the involvement of increased oxidative stress in the pathophysiology of diabetes has raised interest in the potential therapeutic benefit of antioxidants. Although beneficial metabolic effects of antioxidant supplementation have been suggested, an antioxidant mode of action, particularly in skeletal muscle, has not been documented. In the present study, we evaluate the metabolic effects of a gamma-linolenic acid-alpha-lipoic acid conjugate (GLA-LA) in streptozotocin-induced diabetic rats, and assess its potential mode of action by comparing its effects with equimolar administration of LA and GLA alone. Ten days of oral supplementation of 20 mg/kg body weight GLA-LA, but not LA or GLA alone, caused a mild reduction in fasting blood glucose concentration as compared with vehicle-treated diabetic rats (375 +/- 11 vs. 416 +/- 16 mg/dl, p = 0.03), with no change in fasting plasma insulin levels. A peripheral insulin-sensitizing effect could be observed with GLA-LA, LA, and GLA treatments, as demonstrated by a significant (p < 0.04) 23%, 13%, and 10% reduction, respectively, in the area under the glucose curve following an intravenous insulin tolerance test. This effect was associated with a 67% and 50% increase in GLUT4 protein content in the membranes of gastrocnemius muscle of GLA-LA and LA-treated animals, respectively; however, no change was observed with GLA treatment alone. Interestingly, both GLA-LA and LA treatments corrected a diabetes-related decrease in the gastrocnemius muscle low-molecular-weight reduced thiols content. These data demonstrate insulin-sensitizing properties of the GLA-LA conjugate by distinct mechanisms attributable to each of its components, which are associated with antioxidant effects.

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Neurological effects primarily referable to the central nervous system following severe inhalation of methyl bromide have frequently been reported. The patient described in this study developed an unusual early peripheral neuropathy following dermal exposure. Peripheral neuropathy can be an outcome of methyl bromide intoxication, but is usually a late sequela of acute central nervous system toxicity or an aftereffect of repetitively inhaled chronic exposure. In this case, exposure to methyl bromide through abraded skin caused early peripheral neuropathy and central nervous system toxicity.