Pharmacokinetics,pharmacodynamics, toxicology and therapeutics of mavacoxib in the dog: a review

Mavacoxib is a novel nonsteroidal anti‐inflammatory drug (NSAID), with a preferential action on the cyclooxygenase (COX)‐2 isoform of COX and a long duration of action. It is classified chemically as a member of the sulphonamide subgroup of coxibs. Mavacoxib is highly lipid but very poorly water soluble. In the dog, the pharmacokinetic (PK) profile comprises very slow body clearance, long elimination half‐life and a relatively large distribution volume. Biotransformation and renal excretion are very limited, and elimination occurs primarily by biliary secretion and excretion of unchanged drug in faeces. The PK profile of mavacoxib differs quantitatively between young healthy dogs (Beagles and mongrels) and clinical cases with osteoarthritis (OA). In OA dogs, mavacoxib exhibits a much longer terminal half‐life, associated principally with their greater median body weight compared with dogs used in preclinical studies. There is also some evidence of breed differences and a small effect of age on mavacoxib PK in the OA canine population. The pharmacodynamics (PD) of mavacoxib has been established: (i) in whole blood assays at the molecular level (inhibition of COX‐1 and COX‐2 isoforms); (ii) in preclinical models of inflammation and pain; and (iii) in clinical OA subjects treated with mavacoxib. The dosage schedule of mavacoxib for clinical use has been determined by owner and veterinary clinical assessments and is supported by integration of PK and PD preclinical data with clinical responses in canine disease models and in dogs with naturally occurring OA. The dosage regimen has been further confirmed by correlating levels of inhibition of COX isoforms in in vitro whole blood assays with plasma concentrations of mavacoxib achieved in OA dogs. In addition to the specific properties of mavacoxib, some general aspects of the PK and PD of other agents of the NSAID group, together with pathophysiological and clinical aspects of OA, are reviewed, as a basis for correlating with the safety and efficacy of mavacoxib in therapeutic use. Integration of PK and PD data suggests that the recommended dosage regimen of 2 mg/kg bw once for 14 days, followed by administration at monthly intervals, is optimal from both efficacy and safety perspectives and is further confirmed by clinical field studies.     

Near-field deformation from the El Mayor-Cucapah earthquake revealed by differential LIDAR

Large [moment magnitude (M(w)) ≥ 7] continental earthquakes often generate complex, multifault ruptures linked by enigmatic zones of distributed deformation. Here, we report the collection and results of a high-resolution (≥nine returns per square meter) airborne light detection and ranging (LIDAR) topographic survey of the 2010 M(w) 7.2 El Mayor-Cucapah earthquake that produced a 120-kilometer-long multifault rupture through northernmost Baja California, Mexico. This differential LIDAR survey completely captures an earthquake surface rupture in a sparsely vegetated region with pre-earthquake lower-resolution (5-meter-pixel) LIDAR data. The postevent survey reveals numerous surface ruptures, including previously undocumented blind faults within thick sediments of the Colorado River delta. Differential elevation changes show distributed, kilometer-scale bending strains as large as ~10(3) microstrains in response to slip along discontinuous faults cutting crystalline bedrock of the Sierra Cucapah.     

Development and validation of monoclonal and polyclonal antibodies for the detection of immunoglobulin G of bottlenose dolphins (Tursiops truncatus).

Antibodies directed against species-specific immunoglobulin G (IgG) have a broad range of applications in serologic and immunologic research and in the development of clinical assays. Validated anti-IgG antibodies for marine mammal species are in short supply. The objective of this study was to produce and validate antibodies with specificity for IgG of the common bottlenose dolphin (Tursiops truncatus). Bottlenose dolphin IgG was purified using protein G. Two mouse monoclonal antibodies and a rabbit polyclonal antibody were developed from mice and rabbits immunized with bottlenose dolphin IgG. The specificity of the monoclonal antibodies and the polyclonal antibody for bottlenose dolphin IgG was first verified by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). For further validation, both monoclonal antibodies and the polyclonal antibody were incorporated in an indirect ELISA for the detection of the immune response of bottlenose dolphins to a vaccine antigen. Three bottlenose dolphins were immunized with a commercial Erysipelothrix rhusiopathiae vaccine, and serial blood samples were collected from all dolphins for measurement of levels of circulating antibodies. Seroconversion was observed in all 3 dolphins by use of both monoclonal antibodies and the polyclonal antibody. Circulating antibodies were detectable as early as 6 days after immunization in 1 dolphin. Peak antibody levels were detected 14 days after the immunization. The ability to detect seroconversion in all 3 immunized bottlenose dolphins firmly establishes the specificity of the monoclonal antibodies and the polyclonal antibody for IgG of the common bottlenose dolphin.     

Stand restoration burning in oak–pine forests in the southern Appalachians: effects on aboveground biomass and carbon and nitrogen cycling

Understory prescribed burning is being suggested as a viable management tool for restoring degraded oak–pine forest communities in the southern Appalachians yet information is lacking on how this will affect ecosystem processes. Our objectives in this study were to evaluate the watershed scale effects of understory burning on total aboveground biomass, and the carbon and nitrogen pools in coarse woody debris (CWD), forest floor and soils. We also evaluated the effects of burning on three key biogeochemical fluxes; litterfall, soil CO₂ flux and soil net nitrogen mineralization. We found burning significantly reduced understory biomass as well as the carbon and nitrogen pools in CWD, small wood and litter. There was no significant loss of carbon and nitrogen from the fermentation, humus and soil layer probably as the result of low fire intensity. Burning resulted in a total net loss of 55 kg ha⁻¹ nitrogen from the wood and litter layers, which should be easily replaced by future atmospheric deposition. We found a small reduction in soil CO₂ flux immediately following the burn but litterfall and net nitrogen mineralization were not significantly different from controls throughout the growing season following the burn. Overall, the effects of burning on the ecosystem processes we measured were small, suggesting that prescribed burning may be an effective management tool for restoring oak–pine ecosystems in the southern Appalachians.     

An all-in-one dry chemistry immunoassay for the screening of coccidiostat nicarbazin in poultry eggs and liver

An automated immunoassay for the detection of nicarbazin residues in poultry eggs and liver was developed. The assay was based on a novel all-in-one dry chemistry concept and time-resolved fluorometry. The analyte specific antibody was immobilized into a single microtiter well and covered with an insulation layer, on top of which the label was dried in a small volume. The extracted sample was added automatically to the dry microtiter well, and the result was available within 18 min. Due to the rapidity and simplicity, the quantitative immunoassay could also be used as a high throughput screening method. The analytical limit of detection for the assay was calculated as 0.1 ng mL(-)(1) (n = 12) and the functional limit of detection as 3.2 ng g(-)(1) for egg (n = 6) and 11.3 ng g(-)(1) for liver (n = 6) samples. The sample recovery varied from 97.3 to 115.6%. Typically, the intra-assay variations were less than 10%, and interassay variations ranged between 8.1 and 13.6%.