Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells and smooth muscle, and subepithelial fibrosis. We examined the role of leukotrienes in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 and 14, received intranasal OVA periodically Days 14-75. The OVA-treated mice developed an extensive eosinophil and mononuclear cell inflammatory response, goblet cell hyperplasia, and mucus occlusion of the airways. A striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated controls. The cysteinyl leukotriene(1) (CysLT(1)) receptor antagonist montelukast significantly reduced the airway eosinophil infiltration, mucus plugging, smooth muscle hyperplasia, and subepithelial fibrosis in the OVA-sensitized/challenged mice. The presence of Charcot-Leyden-like crystals in airway macrophages and the increased interleukin (IL)-4 and IL-13 mRNA expression in lung tissue and protein in BAL fluid seen in OVA-treated mice were also inhibited by CysLT(1) receptor blockade. These data suggest an important role for cysteinyl leukotrienes in the pathogenesis of chronic allergic airway inflammation with fibrosis.

Antidepressants are a widely prescribed group of pharmaceuticals that can be biotransformed in humans to biologically active metabolites. In the present study, the distribution of six antidepressants (venlafaxine, bupropion, fluoxetine, sertraline, citalopram, and paroxetine) and five of their metabolites was determined in a municipal wastewater treatment plant (WWTP) and at sites downstream of two WWTPs in the Grand River watershed in southern Ontario, Canada. Fathead minnows (Pimephales promelas) caged in the Grand River downstream of a WWTP were also evaluated for accumulated antidepressants. Finally, drinking water was analyzed from a treatment plant that takes its water from the Grand River 17 km downstream of a WWTP. In municipal wastewater, the antidepressant compounds present in the highest concentrations (i.e., >0.5 microg/L) were venlafaxine and its two demethylation products, O- and N-desmethyl venlafaxine. Removal rates of the target analytes in a WWTP were approximately 40%. These compounds persisted in river water samples collected at sites up to several kilometers downstream of discharges from WWTPs. Venlafaxine, citalopram, and sertraline, and demethylated metabolites were detected in fathead minnows caged 10 m below the discharge from a WWTP, but concentrations were all < microg/kg wet weight. Venlafaxine and bupropion were detected at very low (<0.005 microg/L) concentrations in untreated drinking water, but these compounds were not detected in treated drinking water. The present study illustrates that data are needed on the distribution in the aquatic environment of both the parent compound and the biologically active metabolites of pharmaceuticals.

The brominated flame retardants have been subject of a particular environmental focus in the Arctic. The present study investigated the congener patterns and levels of total hexabromocyclododecane (HBCD), polybrominated biphenyls, polybrominated diphenyl ethers (PBDEs), as well as methoxylated (MeO) and hydroxylated (OH) PBDEs in plasma samples of glaucous gulls (Larus hyperboreus) and polar bears (Ursus maritimus) from the Norwegian Arctic. The analyses revealed the presence of total HBCD (0.07-1.24 ng/g wet wt) and brominated biphenyl 101 (< 0.13-0.72 ng/g wet wt) in glaucous gull samples whereas these compounds were generally found at nondetectable or transient concentrations in polar bears. Sum (sigma) concentrations of the 12 PBDEs monitored in glaucous gulls (range: 8.23-67.5 ng/g wet wt) surpassed largely those of polar bears (range: 2.65-9.72 ng/g wet wt). Two higher brominated PBDEs, BDE183 and BDE209, were detected, and thus bioaccumulated to a limited degree, in glaucous gulls with concentrations ranging from < 0.03 to 0.43 ng/g wet wt and from < 0.05 to 0.33 ng/g wet wt, respectively. In polar bear plasma, BDE183 was < 0.04 ng/g wet wt for all animals, and BDE209 was only detected in 7% of the samples at concentrations up to 0.10 ng/g wet wt. Of the 15 MeO-PBDEs analyzed in plasma samples, 3-MeO-BDE47 was consistently dominant in glaucous gulls (sigmaMeO-PBDE: 0.30-4.30 ng/g wet wt) and polar bears (sigmaMeO-PBDE up to 0.17 ng/g wet wt), followed by 4'-MeO-BDE49 and 6-MeO-BDE47. The 3-OH-BDE47, 4'-OH-BDE49, and 6-OH-BDE47 congeners were also detected in glaucous gulls (sigmaOH-PBDE up to 1.05 ng/g wet wt), although in polar bears 4'-OH-BDE49 was the only congener quantifiable in 13% of the samples. The presence of MeO- and OH-PBDEs in plasma of both species suggests possible dietary uptake from naturally occurring sources (e.g., marine sponges and green algae), but also metabolically derived biotransformation of PBDEs such as BDE47 could be a contributing factor. Our findings suggest that there are dissimilar biochemical mechanisms involved in PCB and PBDE metabolism and accumulation/elimination and/or OH-PBDE accumulation and retention in glaucous gulls and polar bears.