Depleted uranium is not toxic to rat brain endothelial (RBE4) cells

Abstract: Studies on Gulf War veterans with depleted uranium (DU) fragments embedded in their soft tissues have led to suggestions of possible DU-induced neurotoxicity. We investigated DU uptake into cultured rat brain endothelial cells (RBE4). Following the determination that DU readily enters RBE4 cells, cytotoxic effects were analyzed using assays for cell volume increase, heat shock protein 90 (Hsp90) expression, 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) reduction, and lactate dehydrogenase (LDH) activity. The results of these studies show that uptake of the U 3 O 8 uranyl chloride form of DU into RBE4 cells is efficient, but there are little or no resulting cytotoxic effects on these cells as detected by common biomarkers. Thus, the present experimental paradigm is rather reassuring and provides no indication for overt cytotoxicity in endothelial cells exposed to DU. Index Entries: Depleted uranium (DU); heavey metal toxicity; blood-brain barrier; endothelium. Article: INTRODUCTION Depleted uranium (DU) is a component of military munitions and is therefore the subject of important toxicity studies. Specifically, the possibility of DU neurotoxicity is under investigation. DU is a dense heavy metal used without reserve in many military applications. Chemically similar to natural uranium, but depleted of much of the radioactivity of the 235 U and 234 U isotopes, DU is a low-specific-activity metal that has several advantages for use as weapons material. Neurotoxicity could potentially arise from the chemical or radioactive properties of DU, and the level of neurotoxicity is as yet undetermined (1-3). Gulf War veterans with DU fragments embedded in their soft tissues were studied and the results suggested that there might be DU-associated effects on behavior and cognition (1-4). Rats embedded with DU fragments accumulated uranium in a range of tissues, with early levels highest in the kidney and a gradual increase in bone accumulation. Brain tissues were found to have far lower levels, with the hippocampus showing high levels among the brain regions following physiologically relevant exposures and cerebellum accumulating the highest levels upon extremely high exposure levels For a blood-borne contaminant to cause neurotoxicity, it must first cross the blood-brain barrier (BBB). This barrier protects the central nervous system (CNS) from toxicants in the blood, and its ability to protect against metal neurotoxicity was reviewed by Zheng et al. (7). The capillaries of the brain are lined with endothelial cells acting as the first line of defense in the BBB. The high degree of tightness of the junctions that link the endothelial cells virtually prevents any paracellular passage from occurring in physiological conditions. In addition, several transport proteins can increase the brain-to-blood efflux of various compounds (e.g., Pglycoproteins or multidrug resistance proteins [MDR] of the ATP-binding cassette [ABC]) (7). The molecula

Activating mutations of STAT5B and STAT3 in lymphomas derived from gamma delta-T or NK cells

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World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update – XIV – Recommendations on CMA immunotherapy

The prevalence of cow's milk allergy (CMA) is approximately 2-4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects