In vitro and ex vivo inhibition of canine cyclooxygenase isoforms by robenacoxib: A comparative study

In vitro whole blood canine assays were used to quantify the inhibitory actions of the novel non-steroidal anti-inflammatory drug (NSAID) robenacoxib on the cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, in comparison with other drugs of the NSAID class. COX-1 activity was determined by measuring serum thromboxane (Tx)B₂ synthesis in blood samples allowed to clot at 37 °C for 1 h. COX-2 activity was determined by measuring prostaglandin (PG)E₂ synthesis in blood samples incubated at 37 °C for 24 h in the presence of lipopolysaccharide. The rank order of selectivity for inhibition of COX-2 versus COX-1 (IC₅₀ COX-1:IC₅₀ COX-2) for veterinary drugs was highest with robenacoxib (128.8) compared to deracoxib (48.5), nimesulide (29.2), S+ carprofen (17.6), meloxicam (7.3), etodolac (6.6), R? carprofen (5.8) and ketoprofen (0.88). Selectivity expressed as the clinically relevant ratio IC₂₀ COX-1:IC₈₀ COX-2 was highest for robenacoxib (19.8) compared to deracoxib (2.3), S+ carprofen (2.5), R? carprofen (2.1), nimesulide (1.8), etodolac (0.76), meloxicam (0.46) and ketoprofen (0.21).An in vivo pharmacokinetic ex vivo pharmacodynamic study in the dog established dosage and concentration–effect relationships for single oral doses of robenacoxib over the dosage range 0.5–8.0 mg/kg. Values of C_max and AUC were linearly related to dosage over the tested range. Robenacoxib did not inhibit serum TxB₂ synthesis (COX-1) ex vivo at dosages of 0.5–4.0 mg/kg and produced only transient inhibition (at the 1 h and 2 h sampling times) at the 8 mg/kg dosage. All dosages of robenacoxib (0.5–8 mg/kg) produced marked, significant and dose related inhibition of PGE₂ synthesis (COX-2) ex vivo.The data demonstrate that in the dog robenacoxib is a highly selective inhibitor of the COX-2 isoform of COX, and significantly inhibits COX-2 and spares COX-1 in vivo when administered orally over the dosage range 0.5–4.0 mg/kg.     

Retrospective evaluation of episodic collapse in the horse in a referred population: 25 cases (1995-2009)

Background: Episodic collapse in horses has equine welfare and human safety implications. There are, however, no published case series describing this syndrome. Objectives: To characterize the cause and outcomes for horses referred for investigation of episodic collapse. Animals: Twenty‐five horses referred for investigation of single or multiple episodes of collapse. Methods: Retrospective study. Clinical records from the Dick Vet Equine Hospital, University of Edinburgh from November 1995 to July 2009 were searched using the following keywords: collapse, collapsing, fall, syncope. Collapse was defined as an incident in which the horse lost postural tone with or without progression to recumbency and with or without loss of consciousness. Long‐term follow‐up information was obtained by telephone conversation with the owner. Results: A final diagnosis was reached in 11 cases, namely cardiac arrhythmia (4), right‐sided heart failure (1), hypoglycemia (2), generalized seizures (2), and sleep disorder (2). A presumptive diagnosis was reached in 8 cases, namely neurocardiogenic syncope (5), exercise‐induced pulmonary hemorrhage (2), and generalized seizures (1). No diagnosis was reached in 6 cases despite comprehensive investigations. Three horses were euthanized at presentation. Treatment was attempted in 9 horses with 6 cases having successful outcome before discharge. Follow‐up information was available for 14 of 19 horses discharged from the hospital. Only 1 of these horses was observed to collapse after discharge. Conclusions and Clinical Importance: Definitive diagnosis was more likely to be reached in cases with multiple episodes of collapse. Horses in which 1 episode of collapse occurred did not necessarily collapse again.     

Accidental entrapment of cats in front-loading washing machines

Two clinical cases of accidental entrapment of cats in front-loading washing machines are described. One cat died the day after presentation as a result of aspiration pneumonia and head trauma, despite supportive care. The second cat survived with supportive treatment, but developed dermatologic complications 10 d later.     

The potential contribution of separation technologies to the management of livestock manure

Separation processes have a distinct role in the management of livestock slurries, but it is important to recognise their limitations. Such technology can direct certain manure components into a small volume of a concentrated stream which is useful for the production of organic products in subsequent processes. Equipment generally falls into systems based either on mechanical screening (which can produce a fibrous and seemingly dry product), filtration processes (producing a cake), or sedimentation leading to a sludge product. Although physical separation can remove up to 80% of the total solids content from livestock manures, this will only include a relatively small part of the soluble nutrient and of the reactive organic matter; this is particularly so where separation is based on screens. The complete removal of all suspended matter (total clarification) of an effluent is theoretically possible by settling — a decanter centrifuge will accelerate the process. This can remove most of the phosphorous, especially if coupled with chemical pre-treatment to raise the pH. However, the clarified stream still retains a significant polluting potential in terms of the residual nitrogen content (as ammonia) and potassium. Only membrane separation can greatly reduce the potassium concentration, but such technology is rarely suitable for the farm situation.     

Antiapoptotic activity of bovine herpesvirus type-1 (BHV-1) UL14 protein

Viruses have evolved different strategies to interfere with apoptotic pathways in order to halt cellular responses to infection. One previous study showed that transient transfection of bovine herpesvirus type-1 (BHV-1) UL14 protein is efficient in protecting Madin Darby kidney (MDBK) and human chronic myelogenous leukemia (K562) cells from sorbitol-induced apoptosis. This protein corresponds to a putative protein of BHV-1, which shares aminoacid sequence with a part of the peptide-binding domain conserved in human heat shock protein (HSP70) family. The pBK-CMV-UL14 plasmid transfected MDBK cells treated with sorbitol did not show caspase-3 and caspase-9 activation with respect to non-transfected MDBK cells (UL14 negative). Furthermore, we report that the expression of the full length sequence of BHV-1 UL14 is evident after 7 h of infection of BHV-1 on MDBK cells which were then treated with sorbitol. These results indicate that UL14 gene product has important implications to enhance cell survival in response to apoptotic stimuli.     

Evaluation of an antigen capture ELISA for the early diagnosis of Hypoderma lineatum in cattle under field conditions

An antigen capture or sandwich ELISA (sELISA) was evaluated for the diagnosis of Hypoderma lineatum in cattle under field conditions in northwestern Spain. The kinetics of circulating hypodermin C (HyC) and specific antibodies during the course of natural infestation were determined in a group of 10 Frisian calves. In addition, oesophagi and blood samples were taken from 105 cows at a slaughterhouse in order to compare three methods for the diagnosis of H. lineatum: sandwich ELISA for the detection of the antigen HyC (sELISA), indirect ELISA for the detection of antibodies anti-HyC (iELISA) and the detection of first instars (L1) in the oesophagus. In naturally infested cattle, HyC was present in circulation at low levels during the early and late phases of the infestation. However, in the middle phase, coinciding with the presence of L1 in the oesophagus, two peaks of increased HyC concentration were observed. Specific antibodies increased progressively until the first appearance of larvae in warbles on the back. There was no correlation between antigen or antibody levels and the number of grubs in the back. Prevalence of first instars in the oesophagi of slaughtered cows was 21.9% (23/105). The percentage of cattle that were positive for circulating antigen was slightly higher (24.8%), suggesting the recent destruction of migrating larvae in some animals. However, there was no correlation between the number of L1 and HyC levels. With the iELISA, 79% of the animals were positive to Hypoderma, which means that a high percentage of those animals have been exposed to the parasite but they had no apparent current infestation. The sELISA is a good tool to follow larval development within the host; however, the episodic elevation of HyC levels limits the usefulness of this test for the early diagnosis of Hypoderma under field conditions.