Pharmacokinetics of firocoxib in preweaned calves after oral and intravenous administration

The objective of this study was to determine the pharmacokinetics of intravenous and oral firocoxib in 10 healthy preweaned calves. Firocoxib (0.5 mg/kg) was initially administered i.v. to calves, and following a 14‐day washout period, animals received firocoxib orally prior to cautery dehorning. Firocoxib concentrations were determined by liquid chromatography–tandem mass spectrometry. Changes in hematology and plasma chemistry were determined using automated methods. Computer software was used to estimate pharmacokinetic parameters best described with a two‐compartment model for i.v. administration and a one‐compartment model for p.o. administration. Following i.v. dosing, the geometric mean (range) T_1/2K10 and T_1/2β were 6.7 (4.6–9.7) and 37.2 (23.5–160.4) h, respectively, V_ss was 3.10 (2.10–7.22) L/kg, and CL was 121.7 (100.1–156.7) mL/h/kg. Following oral administration, geometric mean (range) C_max was 127.9 (102.5–151.3) ng/mL, T_max was 4.0 (2.6–5.6) h, and T_1/2K10 was 18.8 (14.2–25.5) h. Bioavailability of oral firocoxib was calculated using the AUC derived from both study populations to be 98.4% (83.1–117.6%). No adverse clinical effects were evident following firocoxib administration. Pharmacokinetic analysis of i.v. and p.o. firocoxib indicates high bioavailability and a prolonged terminal half‐life in preweaned calves.     

Retrospective study of the relationships between age, inflammation and the isolation of bacteria from the lower respiratory tract of thoroughbred horses

A total of 1235 tracheal aspirates taken from 724 thoroughbreds in race training, aged from two to 10 years, were examined cytologically and bacteriologically. An inflammation scoring system on a scale of 0 to 9 was devised to allow the severity of lower airway disease to be assessed from the cytological results. The inflammation scores were closely related to the isolation of bacteria (P<0.001), and the most common bacterial isolates were Streptococcus zooepidemicus, Streptococcus pneumoniae and Pasteurella/Actinobacillus-like species. Lower airway disease was less common in older horses (P = 0.031), and the groups at highest risk were the two- and four-year-olds. Lower airway inflammation was more common in the four-year-olds at National Hunt yards than in the four-year-olds at flat racing yards (P = 0.040, odds ratio = 3.80).     

The effect of adipocyte and heart fatty acid-binding protein genes on intramuscular fat and backfat content in Meishan crossbred pigs

Effects of genetic variation in porcine adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, respectively, on intramuscular fat (IMF) content and backfat thickness (BFT) were examined in F2 crossbreds of Meishan and Western pigs. The involvement of each FABP gene in IMF accretion was studied to confirm previous results for Duroc pigs. The F2 crossbred pigs were genotyped for various markers including microsatellite sequences situated within both FABP genes. Linkage analysis assigned the A-FABP and H-FABP genes to marker intervals S0001-S0217 (20 cM) on SSC4 and Sw316-S0003 (16.6 cM) on SSC6, respectively, refining previous chromosomal assignments. Next, the role of both chromosome regions/genes on genetic variation in IMF content and BFT was studied by 1) screening SSC4 and SSC6 for QTL affecting both traits by performing a line-cross analysis and 2) estimation of the effect of individual A-FABP and H-FABP alleles on both traits. In the first analysis, suggestive and chromosome-wise significant evidence for a QTL affecting IMF was detected on SSC6. The H-FABP gene is a candidate gene for this effect because it resides within the large region containing this putative QTL. The second analysis showed a considerable but nonsignificant effect of H-FABP microsatellite alleles on IMF content. Suggestive evidence for a QTL affecting BFT was found on SSC6, but H-FABP was excluded as a candidate gene. In conclusion, present and previous results support involvement of H-FABP gene polymorphisms in IMF accretion independently from BFT in pigs. Therefore, implementation of these polymorphisms in marker-assisted selection to control IMF content independently from BFT may be considered. In contrast to previous findings for Duroc pigs, no evidence was found for an effect of the A-FABP gene on IMF or BFT in this population.     

Response to 13 generations of selection for increased 8-week body weight in lines of mice carrying a sheep growth hormone-based transgene

The purpose of this study was to evaluate selection in lines of transgenic mice. Two replicates of lines that either carried or did not carry the sheep metallothionein-1a sheep growth hormone transgene (oMt1a-oGH) were established. The host lines had been previously selected for rapid growth or selected randomly. Within-litter selection for increased 8-wk body weight was carried out for 13 generations. The frequency of oMt1a-oGH was monitored in all generations in the transgenic lines, but no genotypic information regarding the transgene was used as an aid to selection. The oMt1a-oGH was activated from weaning, at 3 wk, until 8 wk of age by adding ZnSO4 to the drinking water. Zinc stimulation of the transgene was not done during mating, gestation, or lactation. Data on body weights and weight gains were analyzed with a conventional mixed model and with an animal model. Genetic progress was achieved in all lines subjected to directional selection. In the control background, response to selection for 8-wk body weight was larger in the nontransgenic lines than in the transgenic lines, whereas no difference was found in the selected background. The frequency of the transgene was increased from the initial .5 to .62 in the randomly selected background but decreased to .04 in lines from a selected background. The REML estimates of variance components and genetic gain estimates varied greatly between the two methods. In general, there was better agreement between the realized heritability estimates and the heritability estimates obtained from the conventional mixed model analysis than between realized heritability estimates and results obtained using the animal model. Favorable correlated responses were obtained for 3- and 6-wk body weights and on 3- to 6- and 6- to 8-wk weight gains. Correlated responses to selection were larger in the selected than in the nonselected background but were not affected by the presence of the transgene. Results suggest that constructs similar to the oMt1a-oGH, which allow tight regulation, may be successfully incorporated into commercial livestock and should have larger effects in populations that have not been subject to selection.     

Aflatoxin B<Subscript>1</Subscript> Binding to Sorbents in Bovine Ruminal Fluid

A recent approach to the problem of contamination of agricultural products by aflatoxin B₁ (AFB₁) is to add non-nutritional adsorbents to animal diets in order to sequester ingested aflatoxins. We conducted in vitro experiments to develop a rapid and cheap model using ruminal fluid to assess the ability of sorbent materials to bind AFB₁. Seven sorbents (hydrated sodium calcium aluminosilicate; clinoptilolite; zeolite; two types of bentonite; sepiolite; and PHIL 75), commonly added to bovine diets were incubated in water and ruminal fluid in the presence of AFB₁. Hydrated sodium calcium aluminosilicate, sepiolite and one of the bentonites bound 100% of the AFB₁ in the presence of both ruminal fluid and water; clinoptilolite bound about 80% of AFB₁ in both liquids; whereas the affinities for the mycotoxin of zeolite (50%) and the other sample of bentonite (60%) in water seem to be increased by about 40% in ruminal fluid incubations. PHIL 75 had the poorest binding ability: about 30% in water and 45% in ruminal fluid. In view of the differences in toxin binding in water and ruminal fluid, it is preferable to use the ruminal fluid model for the in vitro pre-screening of sorbent materials potentially useful as adjuvants to ruminant feeds.     

Subcutaneous administration of paclitaxel in dogs with cancer: A preliminary study

Intravenous paclitaxel has been underused in dogs due to severe and acute hypersensitivity reactions. Subcutaneous (SC) administration of paclitaxel and its safety are unknown. In this preliminary study, SC administration of paclitaxel was evaluated for hypersensitivity reactions and toxicity in 21 dogs with advanced cancer. Dogs received 1 to 5 paclitaxel doses, ranging from 85 to 170 mg/m², SC every 14 or 21 days. A total of 40 paclitaxel doses were administered and none of the 21 dogs developed systemic or acute local hypersensitivity reactions. Severe skin lesions at the injection site developed in 2 dogs after the 4th injection at the same location. Grade 4 neutropenia was observed in 50% of the dogs 5 days after the first treatment at 115 mg/m² (n = 14). Two animals developed Grade 5 diarrhea and died likely due to hemodynamic failure or sepsis. Paclitaxel can be administered SC in dogs with no hypersensitivity reaction.