Development of a synthetic PCB mixture resembling the average polychlorinated biphenyl profile in Chicago air.

Studies of environmental and toxic effects of polychlorinated biphenyls (PCBs) are ideally performed with PCB mixtures reflecting the composition of environmental PCB profiles to mimic actual effects and to account for complex interactions among individual PCB congeners. Unfortunately, only a few laboratory studies employing synthetic PCB mixtures have been reported, in part because of the challenges associated with the preparation of complex PCB mixtures containing many individual PCB congeners. The objective of this study was to develop a PCB mixture that resembles the average PCB profile recorded from 1996 to 2002 at a satellite station of the Integrated Atmospheric Deposition Network located at the Illinois Institute of Technology (IIT) in Chicago, Illinois, using commercial PCB mixtures. Initial simulations, using published Aroclor profiles, showed that a mixture containing 65% Aroclor 1242 and 35% Aroclor 1254 was a good approximation of the target profile. A synthetic Chicago air mixture (CAM) was prepared by mixing the respective Aroclors in this ratio, followed by GC/MS/MS analysis. Comparison of the PCB profile of the synthetic mixture with the target profile suggests that the synthetic PCB mixture is a good approximation of the average IIT Chicago air profiles (similarity coefficient cos θ = 0.82; average relative percent difference = 84%). The synthetic CAM was also a reasonable approximation of the average of 184 PCB profiles analyzed in 2007 at 37 sites throughout Chicago as part of the University of Iowa Superfund Basic Research Program (isbrp), with a cos θ of 0.70 and an average relative percent difference of 118%. While the CAM and the two Chicago air profiles contained primarily di- to pentachlorobiphenyls, higher chlorinated congeners, including congeners with seven or eight chlorine atoms, were underrepresented in the synthetic CAM. The calculated TCDD toxic equivalency quotients of the synthetic CAM (2.7 ng/mg PCB) and the IIT Chicago air profile (1.6 ng/mg PCB) were comparable, but lower by two orders of magnitude than the isbrp Chicago air profile (865 ng/mg PCB) due to surprisingly high PCB 126 levels in Chicago air. In contrast, the calculated neurotoxic equivalency quotients of the CAM (0.33 mg/mg PCB) and the two Chicago air profiles (0.44 and 0.30 mg/mg PCB, respectively) were similar. This study demonstrates the challenges and methods of creating and characterizing synthetic, environmental mixtures of PCBs.

Effectiveness of voluntary conservation agreements: case study of endangered whales and commercial whale watching.

The use of voluntary approaches to achieve conservation goals is becoming increasingly popular. Nevertheless, few researchers have quantitatively evaluated their efficacy. In 1998 industry, government agencies, and nongovernmental organizations established a voluntary conservation program for whale watching in the northeast region of the United States, with the intent to avoid collisions with and harassment of endangered whales by commercial and recreational whale-watching vessels. One important aspect of the program was the establishment of 3 speed zones within specific distances of whales. We wanted to determine the level of compliance with this aspect of the program to gauge its efficacy and gain insights into the effectiveness of voluntary measures as a conservation tool. Inconspicuous observers accompanied 46 commercial whale-watching trips from 12 companies in 2003 (n= 35) and 2004 (n= 11). During each trip, vessel position and speed were collected at 5-second intervals with a GPS receiver. Binoculars with internal laser rangefinders and digital compasses were used to record range and bearing to sighted whales. We mapped whale locations with ArcGIS. We created speed-zone buffers around sighted whales and overlaid them with vessel-track and speed data to evaluate compliance. Speeds in excess of those recommended by the program were considered noncompliant. We judged the magnitude of noncompliance by comparing a vessel's maximum speed within a zone to its maximum recorded trip speed. The level of noncompliance was high (mean 0.78; company range 0.74-0.88), some companies were more compliant than others (p= 0.02), noncompliance was significantly higher in zones farther from whales (p < 0.001), and operators approached the maximum speed capabilities of their vessel in all zones. The voluntary conservation program did not achieve the goal of substantially limiting vessel speed near whales. Our results support the need for conservation programs to have quantifiable metrics and frequent evaluation to ensure efficacy.

Hexahydro-1,3,5-trinitro-1,3,5-triazine mineralization by zerovalent iron and mixed anaerobic cultures.

Soil microcosms were used to evaluate the potential benefits of an integrated microbial-Fe0 system to treat groundwater contamination by RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine). Microcosms amended with both Fe0 filings and municipal anaerobic sludge mineralized RDX faster and to a greater extent than separate treatments, with up to 51% 14CO2 recovery after 77 d. The nitroso byproducts 1,3-dinitro-5-nitroso-1,3,5-triazacyclohexane (MNX), 1,3-dinitroso-5-nitro-1,3,5-triazacyclohexane (DNX), and 1,3,5-trinitroso-1,3,5-triazacyclohexane (TNX) were detected in all microcosms, although these compounds never accumulated above 5% of the added RDX on a molar basis. A soluble intermediate that was tentatively identified as methylenedinitramine [(O2NNH)2CH2] was relatively persistent, although it accumulated to a much lower extent in combined-treatment reactors than in sets with Fe0 or sludge alone. Some of the radiolabel was bound to soil and Fe0 and could not be extracted with CH3CN. This fraction, which was recovered by combustion with a biological oxidizer, was also found at lower concentrations in combined-treatment reactors. This work suggests that permeable reactive Fe0 barriers might be an effective approach to intercept and degrade RDX plumes and that treatment efficiency might be enhanced by biogeochemical interactions through bioaugmentation.

Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease.

A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.

Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII.

The genetic mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases resulting from defective catabolism of glycosaminoglycans (GAGs). Echocardiographic abnormalities in dogs with MPS type VII (Sly syndrome, beta-glucuronidase deficiency) included mitral valve thickening and insufficiency, large aortic dimensions in both the long and short axes, and thickened aortic valves. Grossly, at post mortem examination, there was nodular thickening of the mitral valve, a prominent ductus diverticulum, and a dilated aorta with thickened walls. Histologically, cytoplasmic vacuolation was seen in cells of the mitral valves, coronary arteries, and aorta. By electron microscopy, the cells of the mitral valve were packed with electron-lucent cytoplasmic vacuoles. The mean residual activity of beta-glucuronidase in the aorta and myocardium was <1% of normal, the mean hexosaminidase A activity >2. 5 times normal, and the mean GAG concentrations more than twice normal. In three MPS VII dogs that received heterologous BMT at 6 weeks of age, the echocardiographic abnormalities were improved, and the histopathologic and ultrastructural pathology was reduced. In the aorta and myocardium, the mean beta-glucuronidase activity of the BMT group was 4.5% and 11% of normal, respectively, and the hexosaminidase A activity and GAG concentrations were normalized. Bone Marrow Transplantation (2000) 25, 1289-1297.

Two cases of nonconvulsive status epilepticus in association with tiagabine therapy.

We report two patients with intractable partial seizures who developed generalized nonconvulsive status epilepticus (NCSE) after receiving tiagabine (TGB). Neither had a history of absence seizures or generalized epileptic discharges on prior EEG monitoring. Clinicians need to be aware of a possible association between TGB and NCSE.

Metabolic abnormalities in feline Niemann-Pick type C heterozygotes.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal storage disorder in which cholesterol lipidosis results from defective intracellular transport of unesterified cholesterol. The primary molecular defect of NPC is unknown; regulatory mechanisms of cholesterol metabolism are impaired, resulting in retarded esterification of exogenous cholesterol with accumulation of unesterified cholesterol in lysosomes and secondary storage of glycolipids and sphingomyelin. In obligate heterozygotes from a feline NPC model, cultured skin fibroblasts challenged with exogenously derived cholesterol exhibited intermediate rates of cholesterol esterification and accumulation of unesterified cholesterol. Liver lipid analyses of obligate heterozygote cats demonstrated intermediate cholesterol and sphingomyelin concentrations. Vacuolated skin fibroblasts were found in 2 of 3 heterozygote cats, and occasional cortical neurons exhibited intracellular inclusions immunoreactive for GM2-ganglioside. Ultrastructural studies provided evidence of storage in liver and brain. We believe these morphological and biochemical findings are the first example of manifestations of CNS abnormalities in a genetic carrier for a neuronal storage disease.