Pharmacokinetics and metabolism of orally administered firocoxib, a novel second generation coxib, in horses

The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the elimination half-life was 34 h. The area under the curve [AUC(0-tlast)] was 1.8 microg.h/mL for the oral dose and 2.3 microg.h/mL for the intravenous dose. Firocoxib was widely distributed with a volume of distribution value of 1.7 L/kg for the intravenous dose. Biotransformation of firocoxib was via dealkylation and glucuronidation to inactive metabolites, namely descyclopropylmethylfirocoxib and its glucuronide conjugate. Urinary excretion was the major route of elimination, and the clearance rate was 37 mL/h/kg.     

In-hospital development of an aorto-cardiac fistula in a Warmblood gelding with chronic renal disease

A 20-year-old Warmblood gelding presented for evaluation and treatment of ventral oedema and azotaemia of unknown aetiology. On presentation, a diastolic heart murmur was appreciated and echocardiography revealed moderate aortic insufficiency due to chronic degenerative valve disease. The horse was hospitalised and failed to respond to oral and i.v. fluids and diuretics. Following discontinuation of all fluid and diuretic therapy, the horse became acutely agitated and developed monomorphic ventricular tachycardia. The ventricular tachycardia spontaneously converted to normal sinus rhythm, however the heart murmur changed in timing to a right basilar continuous murmur and bounding jugular pulses were noted. Repeat echocardiogram revealed an aorto-cardiac fistula with dissection into the basilar interventricular septum and left-sided chamber volume overload that was not previously present. Attempts at stabilisation were unsuccessful and euthanasia was elected. Post-mortem examination confirmed chronic renal disease of unknown aetiology in addition to an aorto-cardiac fistula originating from the right sinus of Valsalva with subsequent dissection into the basilar interventricular septum.     

MALDI-TOF MS identification of Prototheca algae associated with bovine mastitis

We evaluated the use of MALDI-TOF MS for the identification of 3 major, dairy-associated Prototheca species, namely, Prototheca bovis (formerly P. zopfii genotype 2), P. blaschkeae, and P. ciferrii (formerly P. zopfii genotype 1). The MALDI-TOF MS spectra established for those species were introduced into the reference spectra library of the Bruker Biotyper MALDI-TOF MS analysis software. Next, 31 Prototheca isolates from Holstein cows with mastitis, from herds located in the midwestern area of São Paulo State, Brazil, were subjected to MALDI-TOF MS profiling. MALDI-TOF MS allowed identification of 22 of 27 P. bovis and 3 of 4 P. blaschkeae isolates with scores >2.0, with 5 of 27 P. bovis and 1 of 4 P. blaschkeae isolates identified only to the genus level. With our extended algae database, MALDI-TOF MS can contribute to quick and effective speciation of Prototheca from mastitis cases.     

Development and evaluation of an endoscopic technique permitting rapid visualization of the cardiac region of the porcine stomach.

Our study was designed to ascertain whether a flexible videoscope could be used to efficiently monitor ulcers of the pars esophagea in a large group of grower-finisher swine. Gastroscopy was performed on 2 separate occasions in 32 pigs following anesthesia with intravenous pentobarbital, and ulcers of the pars esophagea were subjectively graded. The pigs were then necropsied. Grades from the second endoscopic examination were compared for agreement with grades derived from gross inspection of the pars esophagea at necropsy, and with grades derived from histopathologic examination of sections of the same region. The pars esophagea was adequately visualized in all endoscopic examinations. The average duration of each examination, from anesthetic induction, was approximately 8 min. Gastroscopy permitted appreciation of a wide range of focal and diffuse superficial and deep ulcerative lesions of the pars esophagea, but failed to unequivocally identify parakeratosis of the pars esophagea. Agreement between endoscopic and subsequent necroscopic and histopathologic gradings of ulcerations was poor. We concluded that the use of a flexible videoscope permitted rapid inspection of the pars esophagea, and was therefore a practical method of experimentally monitoring the progression of spontaneous gastric ulcers in pigs. We also postulated that the poor agreement between endoscopic and postmortem findings occurred because endoscopy was possibly more sensitive at detecting small and superficial ulcerations. However, further studies are needed to verify the accuracy of endoscopic diagnosis of gastric ulcers in the live pig.     

Lipomatous infiltration of the canine salivary gland

Benign connective tumours of the canine salivary glands are rare. This report describes lipomatous infiltration of parotid or submandibular salivary glands in seven dogs in which the glands were enlarged as a result of infiltration by fat cells; they appeared to have been successfully treated by local excision. The precise cause of the lipomatous infiltration in the dogs is unclear but different causes of similar lesions in humans are discussed.     

Corneal concentrations and preliminary toxicological evaluation of an itraconazole/dimethyl sulphoxide ophthalmic ointment

The objectives of this study were to determine the concentration of itraconazole achieved in corneal tissue and aqueous humour after topical application of a 1% itraconazole ointment; to determine the effect of including dimethyl sulphoxide (DMSO) in the ointment on achievable ocular tissue itraconazole concentrations; and to assess if any gross or histopathologic ocular toxicity results from the topical application of 1% itraconazole with or without the addition of DMSO.
The experimental trial consisted of 6 horses considered to have normal eyes. Each horse had one eye treated with 0.3 mL of 1% ultra-micronized itraconazole ointment and the fellow eye with 0.3 mL of 1% itraconazole/30% DMSO ointment. The ointment was applied every 6 h for a total of 28 treatments. Both ointments were well tolerated and no gross or histopathologic abnormalities developed during the trial.
Corneal tissue and aqueous humour concentrations of itraconazole were determined using high performance liquid chromatography. Corneal tissue concentration averaged 1.1 (± 0.4) μg/g in horses treated with the 1% ultra-micronized itraconazole ointment and 7.9 (± 3.3) μg/g for those treated with the 1% itraconazole/30% DMSO ointment; there was a statistically significant difference between ointments ( P = 0.005) No itraconazole could be detected in the aqueous humour in either treatment group.     

Differential responses in anterior pituitary luteinizing hormone (LH) content and LHβ- and α-subunit MRNA, and plasma concentrations of LH and testosterone, in bulls treated with the LH-releasing hormone agonist deslorelin

Anterior pituitary gland contents of LH and LHß- and α-subunit mRNAs, and circulating concentrations of LH and testosterone, were determined in bulls treated with the LH-releasing hormone (LHRH) agonist deslorelin. Brahman (Bos indicus) bulls (14-month-old) were allocated to two groups and received the following: Control (n = 5), no treatment; Deslorelin (n = 4), four deslorelin implants (approximately 200 μg total deslorelin/day) for 36 d. Plasma concentrations of LH were higher in bulls treated with deslorelin on Day 1, had returned to typical levels by Day 8, and did not differ for control bulls and bulls treated with deslorelin from Day 8 to Day 29. Pituitary content of LH on Day 36 was reduced (P < 0.001) in bulls treated with deslorelin (33 ± 4 ng/mg) compared with control bulls (553 ± 142 ng/mg). Relative pituitary content of LHß-subunit mRNA was also reduced on Day 36 in bulls treated with deslorelin (Control, 0.65 ± 0.10; Deslorelin, 0.22 ± 0.04; P = 0.003). However, α-subunit mRNA relative content did not differ (Control, 0.73 ± 0.15; Deslorelin, 1.06 ± 0.12; P > 0.05). Plasma concentrations of testosterone were increased over the period of the experiment in the bulls treated with deslorelin compared with control bulls. This is the first demonstration of reduced pituitary content of LHß-subunit mRNA and LH, and unaltered content of α-subunit mRNA, in bulls treated with LHRH agonist. This was associated with apparently typical plasma concentrations of LH and elevated plasma testosterone. The anterior pituitary in bulls treated with LHRH agonist, therefore, undergoes classical desensitization and downregulation, but plasma LH and testosterone are not suppressed.     

A multivariable prognostic model for equine colic patients

A survey of 1965 equine colic cases was conducted from August 1985 to July 1986 ten equine referral hospitals located througout the U.S.A. Two-thirds of the cases were randomly selected for model development (1336), while the remaining cases (629) were used only for subsequent validation of the model. The following outcomes were defined: (1) died or killed prior to discharge from the hospital; or (2) alive at the time of discharge. Only variables which were significant (P<0.05) in an initial bivariate screening procedure and for which there were less than 400 missing values were considered in the multivariable modelling. A multivariable logistic regression model was constructed using a stepwise algorithm. The model used 666 cases and included the following variables: peripheral pulse (normal or weak), pulse rate, surgical or medical treatment, packed cell volume, self-inflicted trauma (absent or present) and capillary refill time. For each horse in the validation data set which had the appropriate variables recorded (n=335), the estimated expected probability of death (expected value) was calculated using the logistic regression equation. Using Bayes theorem, the post-test probability was calculated from the expected value (an estimate of the test odds) and the present probability (the case-fatality rate at each institution). Nomograms of predictive values for different case-fatality rates and expected values were constructed. Hosmer-Lemeshow goodness-of-fit statistics indicated that the model fitted the model data set well but the validation set poorly. However, when the observed case-fatality rates were compared with the average post-test probabilities for 0.10 increments of post-test probability, qualitatively, the model's performance was better.