Differential pharmacokinetics and pharmacokinetic/pharmacodynamic modelling of robenacoxib and ketoprofen in a feline model of inflammation

Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B₂ concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E₂ concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and robenacoxib, respectively. Both drugs reduced exudate PGE₂ concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB₂ between 4 min and 24 h, whereas suppression was mild and transient with robenacoxib. In vivoIC₅₀COX‐1/IC₅₀COX‐2 ratios were 66.9:1 for robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood.     

Differential distribution and response to experimental sexual maturation of two forms of brain gonadotropin-releasing hormone (GnRH) in the European eel,Anguilla anguilla

Using specific radioimmunoassays for the two GnRH molecular forms present in the European eel, Anguilla anguilla, (mGnRH and cGnRH II), we compared their distributions in the pituitary and different parts of the brain of female silver eels, as well as the modifications of their levels in experimentally matured female eels (treated with carp pituitary extract). In control eels, mGnRH levels were higher than cGnRH II levels in the pituitary, olfactory lobes and telencephalon, di- and mesencephalon, while the opposite was found in the posterior part of the brain (met- and myelencephalon). Experimental sexual maturation of the gonads significantly increased mGnRH levels in the pituitary and anterior parts of the brain; such a positive effect was not observed on the low cGnRH II levels, which were, in contrast, reduced. These data indicate that the positive feedback of gonadal hormones on GnRH, that we previously demonstrated, would specifically affect the mGnRH form. The differential distribution and control of mGnRH and cGnRH II suggest that these two forms have different physiological roles in the eel. The large increase in mGnRH during sexual maturation suggests the prime implication of this form in the neuroendocrine control of reproduction.     

Marine fish life history strategies: applications to fishery management

The life history traits of 42 marine fish species were grouped according to the theoretical classifications of life history strategies. This provides a conceptual framework of management options, because life history strategies are the underlying determinants for population responses to climate and ocean changes, they can be used to classify typical population responses. When faced with providing management advice for species for which there is no information on absolute or relative biomass, such as newly exploited species, life history traits can be used to classify the species into a strategist grouping and the appropriate management options can be selected from the conceptual framework.     

Experimental susceptibility of Atlantic cod, Gadus morhua (L.), and Atlantic halibut, Hippoglossus hippoglossus (L.), to different genotypes of viral haemorrhagic septicaemia virus

Viral haemorrhagic septicaemia (VHS) is a well-characterized disease of rainbow trout, Oncorhynchus mykiss, which has also caused economic losses in marine turbot farms in the British Isles. We have previously demonstrated that turbot, Scophthalmus maximus, are susceptible to isolates of viral haemorrhagic septicaemia virus (VHSV) that are endemic in the marine environment, highlighting a potential risk to marine aquaculture. Given the increasing interest in the intensive rearing of additional aquaculture species such as Atlantic cod, Gadus morhua, and Atlantic halibut, Hippoglossus hippoglossus, this study aimed at investigating the susceptibility of these species to VHSV. Both species were found to be largely resistant to VHS following immersion challenge with a selection of 18 isolates, representing the known marine VHSV genotypes. Only one and two VHSV-associated mortalities occurred out of a total of 1710 and 1254 halibut and cod, respectively. These findings suggest that there is a low direct risk to the development of commercial cod and halibut aquaculture from the existing endemic reservoir of VHSV. This study, coupled to field observations has, however, highlighted the fact that both species can become infected with VHSV. The known adaptability of RNA viruses, together with the selection pressures associated with intensive aquaculture would thus advocate a cautious approach to VHSV surveillance within these emerging industries.     

Effects of dbcAMP on steroidogenesis in isolated ovarian follicles of Atlantic salmon

In vitro estradiol-17β (E₂) and testosterone (T) production were measured in vitellogenic follicles of Atlantic salmon in response to treatment with human chorionic gonadotropin (hCG) and 2-0-dibutyryladenosine 3′,5′-cyclic monophosphate (dbcAMP). DbcAMP stimulated T production but had no effect on E₂, whereas hCG treatment stimulated E₂ production but T production was low. Elevated intracellular [cAMP] may be part of the normal mechanism for inhibition of aromatase activity at the end of vitellogenesis.     

Evaluating changes in switchgrass physiology,biomass, and light-use efficiency under artificial shade to estimate yields if intercropped with Pinus taeda L.

There is growing interest in using switchgrass (Panicum virgatum L.) as a biofuel intercrop in forestry systems. However, there are limited data on the longevity of intercropped bioenergy crops, particularly with respect to light availability as the overstory tree canopy matures. Therefore, we conducted a greenhouse study to determine the effects of shading on switchgrass growth. Four treatments, each with different photosynthetically active radiation (PAR) levels, were investigated inside the greenhouse: control (no shade cloth, 49 % of full sunlight), low (under 36 % shade cloth), medium (under 52 % shade cloth), and heavy shade (under 78 % shade cloth). We determined the effect of shading from March to October 2011 on individually potted, multi-tillered switchgrass transplants cut to a stubble height of 10 cm. In the greenhouse, there was a reduction in tiller number, tiller height, gas exchange rates (photosynthesis and stomatal conductance), leaf area, above- and belowground biomass and light-use efficiency with increasing shade. Total (above- and belowground) biomass in the control measured 374 ± 22 compared to 9 ± 2 g pot^?1 under heavy shade (11 % of full sunlight). Corresponding light-use efficiencies were 3.7 ± 0.2 and 1.4 ± 0.2 g MJ^?1, respectively. We also compared PAR levels and associated aboveground switchgrass biomass from inside the greenhouse to PAR levels in the inter-row regions of a range of loblolly pine (Pinus taeda L.) stands from across the southeastern United States (U.S.) to estimate when light may limit the growth of intercropped species under field conditions. Results from the light environment of loblolly pine plantations in the field suggest that switchgrass biomass will be significantly reduced at a loblolly pine leaf area index between 1.95 and 2.25, which occurs on average between ages 6 and 8 years across the U.S. Southeast in intensively managed pine plantations. These leaf area indices correspond to a 60–65 % reduction in PAR from open sky.     

Phosphorus utilization in rainbow trout (Oncorhynchus mykiss) fed practical diets and its consequences on effluent phosphorus levels

Excessive dietary phosphorous (P) concentrations in effluents from aquaculture present a major environmental problem. We therefore studied the effect of dietary P and vitamin D₃ on P utilization by rainbow trout-fed practical diets and on P concentrations in the soluble, particulate and settleable components of the effluent from fish tanks. Rainbow trout (average weight: 78 g, initial biomass: 13 kg in 0.7 m³ tanks) were fed for 11 weeks, practical diets that varied in total P, available P, and vitamin D₃ concentrations. Soluble, particulate (10–200 μm) and settleable (>200 μm) P in the effluent were sampled every 0.5–6 h for 1–3 days in the third and eleventh weeks of the experiment. Trout in all diets more than doubled their weight after 11 weeks. Increasing the concentrations of available dietary P from 0.24% to 0.88% modestly enhanced growth rate. Feed conversion ratio (FCR) and biomass gain per gram P consumed decreased as dietary P concentrations increased. Carcass P, daily P gain, and plasma P concentrations were lower in fish fed with low P diets. Soluble P concentrations in the effluent peaked immediately after and again 4–6 h after feeding, and is a linear function of available dietary P. No soluble P would be produced during consumption of diets containing less than 0.22±0.02% available P. Above this dietary concentration, soluble P would be excreted at 6.9±0.4 mg/day/kg for each 0.1% increase in available dietary P. Particulate P concentrations in the effluent were independent of dietary P concentrations. Settleable, presumably fecal, P concentrations tended to increase with dietary P concentrations. In trout fed with low P (0.24% available P, 0.6% total P) diets, 60% of total dietary P were retained by the fish and the remaining 40% were excreted in the effluent as settleable P (20–30%) and particulate or soluble P (10–20%). In trout fed with high P (0.59–0.88% available P; 0.9–1.2% total P) diets, 30–55% of total dietary P was retained by fish, and the remaining 15–25% appeared in the effluent as settleable P, 20–55% as soluble P, and 5–10% as particulate P. Vitamin D₃ did not affect fish growth nor effluent P levels. Physicochemical management of aquaculture effluents should consider the effect of diets on partitioning of effluent P, the peaks of soluble P concentration following feeding, and the contributions of particulate P to total P in the effluent. Increasing our understanding of how dietary P is utilized and is subsequently partitioned in the effluent can contribute significantly towards alleviating this important environmental and industry problem.