An aldose reductase inhibitor and aminoguanidine prevent vascular endothelial growth factor expression in rats with long-term galactosemia

OBJECTIVE: To study the effects of an aldose reductase inhibitor (ARI-509, Wyeth-Ayerst, Princeton, NJ) and aminoguanidine (AMG), agents that have been reported to prevent or delay diabetic retinopathy, on retinal vascular abnormalities and the immunocytochemical expression in the retina of vascular endothelial growth factor (VEGF) in rats maintained for up to 2 years on a 50% galactose diet. METHODS: Albino rats were placed on a control diet, a diet containing 50% galactose, or the 50% galactose diet containing either ARI-509 or AMG. Treatment with ARI-509 or AMG was initiated at the beginning of the experiment or after 12 months of galactose feeding. After 22 to 24 months, the rats were killed and the retinal vasculature from half of one eye was isolated by trypsin-elastase digestion for semiquantitative evaluation of retinal vascular lesions. The other half of the retina was prepared for immunocytochemistry and stained for the presence of VEGF, factor VIII, vimentin, and glial fibrillary acidic protein. Red blood cells, sciatic nerves, and a portion of the retina from the second eye were assayed for glucose, galactose, fructose, sorbitol, galactitol, and myo-inositol. Red blood cells were also assayed for galactosylated hemoglobin. RESULTS: Galactose-fed animals developed a vascular retinopathy characterized by severe cellular loss in the retinal capillaries and intensification of periodic acid-Schiff staining of the vascular basement membranes. Some animals also displayed dilation and hypercellularity of vessels in the posterior retina. These changes were substantially reduced in animals receiving ARI-509 from the beginning of the galactose diet, but were unaffected in all of the other treatment groups. None of the rats receiving ARI-509 or AMG treatment, whether initiated from the onset or after 12 months of galactosemia, demonstrated VEGF immunoreactivity. With the exception of the animals receiving ARI-509 from the beginning of the experiment, all of the galactose-fed animals developed dense cataracts within 6 weeks of the beginning of the galactose diet. Galactitol levels in animals receiving ARI-509 were 86% to 93% lower in red blood cells, retina, and sciatic nerve than those in the other galactose-fed groups. CONCLUSIONS: Although ARI-509 and AMG have different abilities to delay or prevent the diabetic-like retinopathy in galactosemic rats, even when substantial retinal microvascular acellularity occurs, both drugs prevent the immunocytochemical expression of VEGF. These results suggest that factors other than hypoxia may be responsible for VEGF expression in the retina, and that aldose reductase inhibitors and AMG have potential roles in preventing such expression and, thus, perhaps preventing retinal neovascularization.     

Limitations on the uses of multimedia exposure measurements for multipathway exposure assessment--Part II: Effects of missing data and imprecision.

Multimedia data from two probability-based exposure studies were investigated in terms of how missing data and measurement-error imprecision affected estimation of population parameters and associations. Missing data resulted mainly from individuals'refusing to participate in certain measurement activities, rather than from field or laboratory problems; it suggests that future studies should focus on methods for maximizing participation rates. Measurement error variances computed from duplicate-sample data were small relative to the inherent variation in the populations; consequently, adjustments in nonparametric percentile estimates to account for measurement imprecision were small. Methods of adjustment based on lognormality assumptions, however, appeared to perform poorly.     

Fungal carriage in lizards

The occurrence of fungi was investigated in the gut of 200 common garden lizards (Agama agama). The most important pathogenic fungus isolated was Basidiobolus haptosporus, an aetiological agent of subcutaneous zygomycosis. It was recovered from the intestinal contents of 112 (56%) lizards. Other important fungi isolated included Aspergillus spp. in 24 (12%) lizards, Candida spp. in 12 (6%), Penicillium spp. in 12 (6%) and Fusarium spp. in 12 (6%). Mucor spp. were isolated from eight (4%) male lizards only. Agamid lizards are plentiful in rural and urban areas of Nigeria. As they live in close vicinity to man, they are likely to play an important role in the spread of disease that may be caused by these fungi and its transmission to man. None of the animals investigated that yielded fungal cultures revealed any external fungal infection.     

Evaluating Ozone as a Remedial Treatment for Removing RDX from Unsaturated Soils

Years of wastewater discharge at the Department of Energy’s Pantex Plant have contaminated the vadose zone and underlying perched aquifer with hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). Because the vadose zone is acting as a continual source of groundwater contamination, removing RDX from the unsaturated zone is paramount to prevent further contamination. We determined the efficacy of ozone to degrade and mineralize RDX. Solution experiments showed that ozone (27?mg?L?1; 150?mL?min?1) was effective in mineralizing 80% of the RDX (30?mg?RDX?L?1) provided that some Pantex soil was present to buffer the solution pH. Soil columns treated with ozone produced 50% RDX mineralization within 1 day and >80% within 7 day. Experiments designed to evaluate aerobic biodegradation following partial ozonation of a RDX solution showed that ozone-generated RDX products were much more biodegradable than untreated controls in aerobic microcosms (35 versus <0.3% cumulative mineralization). These results support the use of ozone as a remedial treatment for the contaminated vadose zone at the Pantex facility.     

The integrated academic information management system at Columbia-Presbyterian Medical Center.

Over the past seven years, Columbia-Presbyterian Medical Center has been planning and implementing an integrated academic information management system. Accomplishments to date include establishing an institutional information architecture, installing a campus-wide network of workstations, recruiting the staff needed to develop and implement the system, and developing various applications. This paper presents the rationale and steps involved in these accomplishments, as well as data on use of the system so far.