Depleted and natural uranium: chemistry and toxicological effects.

Depleted uranium (DU) is a by-product from the chemical enrichment of naturally occurring uranium. Natural uranium is comprised of three radioactive isotopes: (238)U, (235)U, and (234)U. This enrichment process reduces the radioactivity of DU to roughly 30% of that of natural uranium. Nonmilitary uses of DU include counterweights in airplanes, shields against radiation in medical radiotherapy units and transport of radioactive isotopes. DU has also been used during wartime in heavy tank armor, armor-piercing bullets, and missiles, due to its desirable chemical properties coupled with its decreased radioactivity. DU weapons are used unreservedly by the armed forces. Chemically and toxicologically, DU behaves similarly to natural uranium metal. Although the effects of DU on human health are not easily discerned, they may be produced by both its chemical and radiological properties. DU can be toxic to many bodily systems, as presented in this review. Most importantly, normal functioning of the kidney, brain, liver, and heart can be affected by DU exposure. Numerous other systems can also be affected by DU exposure, and these are also reviewed. Despite the prevalence of DU usage in many applications, limited data exist regarding the toxicological consequences on human health. This review focuses on the chemistry, pharmacokinetics, and toxicological effects of depleted and natural uranium on several systems in the mammalian body. A section on risk assessment concludes the review.

Terbutaline is a developmental neurotoxicant: effects on neuroproteins and morphology in cerebellum, hippocampus, and somatosensory cortex.

Beta(2)-adrenoceptor agonists, especially terbutaline, are widely used to arrest preterm labor, but they also cross the placenta to stimulate fetal beta-adrenoceptors that control neural cell differentiation. We evaluated the effects of terbutaline administration in neonatal rats, a stage of neurodevelopment corresponding to human fetal development. Terbutaline administered on postnatal days PN2 to 5 elicited neurochemical changes indicative of neuronal injury and reactive gliosis: immediate increases in glial fibrillary acidic protein and subsequent induction of the 68-kDa neurofilament protein. Quantitative morphological evaluations carried out on PN30 indicated structural abnormalities in the cerebellum, hippocampus, and somatosensory cortex. In the cerebellum, PN2 to 5 terbutaline treatment reduced the number of Purkinje cells and elicited thinning of the granular and molecular layers. The hippocampal CA3 region also displayed thinning, along with marked gliosis, effects that were restricted to females. In the somatosensory cortex, terbutaline evoked a reduction in the proportion of pyramidal cells and an increase in smaller, nonpyramidal cells; again, females were affected more than males. Although abnormalities were obtained with later terbutaline treatment (PN11 to 14), in general the effects were smaller than those seen with PN2 to 5 exposure. Our results indicate that terbutaline is a neurotoxicant that elicits biochemical alterations and structural damage in the immature brain during a critical period. These effects point to a causal relationship between fetal terbutaline exposure and the higher incidence of cognitive and neuropsychiatric disorders reported for the offspring of women receiving terbutaline therapy for preterm labor.

Expression of functional estrogen receptor beta in locus coeruleus-derived Cath.a cells.

Estrogen may have an important role in the brain beyond the development and regulation of reproductive function. Gender differences in the incidence of depression suggest that regulation of mood represents one such action. The locus coeruleus, a brain stem noradrenergic nucleus implicated in mood regulation, concentrates [(3)H]estradiol, but expression of the two estrogen receptor (ER) subtypes (ERalpha and ERbeta) varies across species. Further, the role of each subtype in estrogen action on noradrenergic neurons is unknown. We examined the expression of ERs in the Cath.a (central-adrenergic-tyrosine-hydroxylase-expressing) cell line derived from mouse brain stem and found that they express ERbeta protein but not ERalpha protein. Transient transfection assays using an estrogen-responsive reporter gene indicate that ERbeta is functional. The pure estrogen antagonist ICI 182,780 completely abolished estrogen's effects. Selective ER modulator results suggest that ER in Cath.a cells behaves in a manner consistent with ERbeta pharmacology. R,R-Tetrahydrochrysene, an ERalpha agonist, had no effect on luciferase-driven activity in Cath.a cells. This study provides the first report of a cell line that spontaneously expresses functional ERbeta protein. Cath.a cells may prove to be a useful tool in elucidating basic pharmacologic properties of ERbeta. It may also help reveal the molecular mechanisms involved in mood regulation by estrogen.