Blood-brain barrier function, cell viability, and gene expression of tight junction-associated proteins in the mouse are disrupted by crude oil, benzo[a]pyrene, and the dispersant COREXIT.

Exposure to crude oil, its components, and oil dispersants during a major crude oil spill, such as the Deepwater Horizon Oil Spill, can elicit behavioral changes in animals and humans. However, the underlying mechanisms by which oil spill-related compounds alters behavior remains largely unknown. A major cause of behavioral changes generally is dysfunction of the blood-brain barrier (BBB). We investigated the impact of a crude oil high energy water accommodated fraction (HEWAF), benzo[a] pyrene (BaP; a major component of crude oil), and the oil dispersant COREXIT, on BBB function. BBB function was assessed by measuring transendothelial electrical resistance (TEER) of mouse brain microvascular endothelial cells (BMECs). Within 3 h after treatment, TEER was significantly reduced by exposure to high concentrations of all test compounds. TEER remained reduced in response to COREXIT after 48 h, but this effect waned in BMECs treated with HEWAF and BaP, with low-mid range concentrations inducing increased TEER compared to vehicle controls. At 48 h of treatment, BMEC viability was significantly reduced in response to 2% HEWAF, but was increased in response to BaP (25 and 50 µM). BMEC viability was increased with 80 ppm COREXIT, but was reduced with 160 ppm. Gene expression of tight junction-associated proteins (claudin-5 and tight junction protein-1), and cell adhesion receptor (vascular cell adhesion molecule-1) was reduced in response to HEWAF and COREXIT, but not BaP. Taken together, these data suggest that oil spill-related compounds markedly affect BBB function, and that these changes may underlie the observed behavioral changes due to crude oil exposure.

In vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole on Malassezia organisms from dogs with otitis externa.

The purpose of this study was to evaluate the in vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole in purified water on Malassezia organisms from dogs with otitis externa. Malassezia organisms were collected from ear swab samples from the external ear canal of 19 dogs with otitis externa plus one control strain of Malassezia pachydermatis. Three test solutions were evaluated: ER (EDTA, tromethamine, benzyl alcohol), ER + keto (EDTA, tromethamine, benzyl alcohol, ketoconazole), and H2O (purified water). Ten-millilitre aliquots of each test solution was transferred into 20 tubes and inoculated with one of the isolates (1 tube per isolate: 19 clinical and 1 control strain). Samples were retrieved from each tube at five time points (0, 15, 30, 45 and 60 min), transferred to Petri dishes, mixed with Sabouraud dextrose agar supplemented with 0.5% Tween 80 and incubated. Following incubation, the plates were examined for growth and colonies counted as colony-forming units per millilitre. The data were analysed using a repeated measures analysis, with pair-wise comparisons of solution-time combinations. There was a significant reduction in Malassezia growth in ER + keto at all time points (P < 0.0001) compared to time zero. Neither ER nor H2O had any effect on the growth of Malassezia. ER + keto was significantly more effective in reducing Malassezia growth (P < 0.0001) at all time points compared to both ER and H2O. ER + keto may be useful in the treatment of Malassezia otitis externa. Future studies should be performed to evaluate the in vivo efficacy of ER + keto as treatment for otic infections caused by Malassezia.

Controlled trial of nimodipine in amyotrophic lateral sclerosis.

Calcium channel blocking drugs antagonize excitatory amino acid receptor activation, decrease calcium entry into damaged neurons, and might help to slow or reverse amyotrophic lateral sclerosis (ALS). We enrolled 87 patients with ALS in a randomized, placebo-controlled, prospective, double-blind crossover study of nimodipine therapy. Monthly measures of isometric muscle strength and respiratory function compared the effects of drug and placebo. No difference in adverse events occurred in placebo vs drug-treated patients, but diarrhoea, nausea, and lightheadedness were more common with nimodipine. There was no significant difference in the rate of decline of pulmonary function or limb strength during treatment with drug or placebo. Nimodipine was ineffective in slowing the progress of ALS.