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Background: Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a high-energy, trinitrated cyclic compound that has been used worldwide since World War II as an explosive in both military and civilian applications. RDX can be released in the environment by way of waste streams generated during the manufacture, use, and disposal of RDX-containing munitions and can leach into groundwater from unexploded munitions found on training ranges. For > 60 years, it has been known that exposure to high doses of RDX causes generalized seizures, but the mechanism has remained unknown., Objective: We investigated the mechanism by which RDX induces seizures., Methods and Results: By screening the affinity of RDX for a number of neurotransmitter receptors, we found that RDX binds exclusively to the picrotoxin convulsant site of the γ-aminobutyric acid type A (GABA(A)) ionophore. Whole-cell in vitro recordings in the rat basolateral amygdala (BLA) showed that RDX reduces the frequency and amplitude of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic currents and the amplitude of GABA-evoked postsynaptic currents. In extracellular field recordings from the BLA, RDX induced prolonged, seizure-like neuronal discharges., Conclusions: These results suggest that binding to the GABA(A) receptor convulsant site is the primary mechanism of seizure induction by RDX and that reduction of GABAergic inhibitory transmission in the amygdala is involved in the generation of RDX-induced seizures. Knowledge of the molecular site and the mechanism of RDX action with respect to seizure induction can guide therapeutic strategies, allow more accurate development of safe thresholds for exposures, and help prevent the development of new explosives or other munitions that could pose similar health risks.

Immunoreactive insulin was measured in amniotic fluid from Rh-immunized women (anti-D antibody). The degree of immunization was expressed by the spectrophotometric index of the amniotic fluid and by the capillary hemoglobin concentration of the newborn. Higher levels of insulin were found in amniotic fluid from severely Rh-immunized mothers than from non-immunized, and a correlation between the degree of immunization and insulin concentration was indicated. To our knowledge this has not previously been demonstrated, and may justify some new hypotheses concerning the pathogenesis of the observed higher frequency of hyperinsulinism in babies of Rh-immunized mothers.