Identifying degradation products responsible for increased toxicity of UV-Degraded insensitive munitions.

Degradation of insensitive munitions (IMs) by ultraviolet (UV) light has become a topic of concern following observations that some UV-degradation products have increased toxicity relative to parent compounds in aquatic organisms. The present investigation focused on the Army's IM formulation, IMX-101, which is composed of three IM constituents: 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ). The IM constituents and IMX-101 were irradiated in a UV photo-reactor and then administered to Daphnia pulex in acute (48 h) exposures comparing toxicities relative to the parent materials. UV-degradation of DNAN had little effect on mortality whereas mortality for UV-degraded NTO and NQ (and associated degradation products) increased by factors of 40.3 and 1240, respectively, making UV-degraded NQ the principle driver of toxicity when IMX-101 is UV-degraded. Toxicity investigations for specific products formed during UV-degradation of NQ, confirmed greater toxicity than the parent NQ for degradation products including guanidine, nitrite, ammonia, nitrosoguanidine, and cyanide. Summation of the individual toxic units for the complete set of individually measured UV-degradation products identified for NQ only accounted for 25% of the overall toxicity measured in the exposures to the UV-degraded NQ product mixture. From these toxic unit calculations, nitrite followed by CN- were the principal degradation products contributing to toxicity. Given the underestimation of toxicity using the sum toxic units for the individually measured UV-degradation products of NQ, we conclude that: (1) other unidentified NQ degradation products contributed principally to toxicity and/or (2) synergistic toxicological interactions occurred among the NQ degradation product mixture that exacerbated toxicity.

Glycated albumin and risk of death and hospitalizations in diabetic dialysis patients.

BACKGROUND AND OBJECTIVES: Relative to hemoglobin (Hb) A(1c), glycated albumin (GA) more accurately reflects glycemic control in patients with diabetes mellitus and ESRD. We determined the association between GA, HbA(1c), and glucose levels with survival and hospitalizations in diabetic dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Quarterly GA levels were measured for up to 2.33 years in 444 prevalent patients with diabetes and ESRD. Proportional hazard time-dependent covariate models were computed with adjustment for demographic characteristics, comorbidities, and laboratory variables. Similar analyses were performed for available HbA(1c) and monthly random serum glucose determinations. RESULTS: The participants were 53% male, 54% African American, 43% Caucasian, 90% on hemodialysis, with a mean (SD) age of 62 (12) years and median follow-up duration of 2.25 years. GA and HbA(1c) mean ± SD 21.5% ± 6.0%, median 20.4% and mean ± SD 6.9% ± 6.6%, median 1.6%, respectively. There were 156 deaths during the observation period. In best-fit models, predictors of death included increasing GA, increasing age, presence of peripheral vascular disease, decreasing serum albumin, and decreasing hemoglobin concentrations. HbA(1c) and random serum glucose concentrations were not predictive of survival. Increasing GA levels were associated with hospitalization in the 17 days after measurement, whereas HbA(1c) was not. CONCLUSIONS: In contrast to the HbA(1c) and random serum glucose values, GA accurately predicts the risk of death and hospitalizations in patients with diabetes mellitus and ESRD. The GA assay should be considered by clinicians who care for patients with diabetes on dialysis.

High-field magnetic resonance imaging of brain iron in Alzheimer disease.

OBJECTIVES: Increased iron deposition in the brain may occur in several neurodegenerative diseases, including Alzheimer disease (AD). Iron deposits shorten T2 relaxation times on T2-weighted magnetic resonance (MR) images. Iron-dependent contrast increases with magnetic field strength. We hypothesized that T2 mapping using 3 T MR imaging (MRI) can disclose differences between normal controls and AD subjects. METHODS: High-resolution brain imaging protocols were developed and applied to 24 AD patients and 20 age-matched controls using 3 T MRI. Eight anatomical regions of interest were manually segmented, and T2 histograms were computed. A visual analysis technique, the heat map, was modified and applied to the large image data sets generated by these protocols. RESULTS: A large number (163) of features from these histograms were examined, and 38 of these were significantly different (P < 0.05) between the groups. In the hippocampus, evidence was found for AD-related increases in iron deposition (shortened T2) and in the concentration of free tissue water (lengthened T2). Imaging of a section of postmortem brain before and after chemically extracting the iron established the presence of MRI-detectable iron in the hippocampus, cortex, and white matter in addition to brain regions traditionally viewed as containing high iron concentrations.