In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis

OBJECTIVE: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs. ANIMALS: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles. PROCEDURE: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis. RESULTS: Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis. CONCLUSIONS AND CLINICAL RELEVANCE: ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.     

Changes in light intensity can influence age at sexual maturity in domestic pullets

1. Shaver White and ISA Brown pullets were reared to 140 d in groups of 8 in cages on a 10-h photoperiod of incandescent light and maintained at an illuminance of 3 or 25 lux, or transferred from 3 to 25 lux or from 25 to 3 lux at 63 or 112 d of age. 2. There was no significant difference in sexual maturity, measured as eggs per 100 bird.d at 139 and 140 d, for ISA Brown maintained on 3 or 25 lux, but Shaver White pullets exposed to constant 3 lux matured significantly later than those maintained on 25 lux. 3. In Shaver Whites, sexual maturity was significantly delayed by an increase from 3 to 25 lux at 63 and 112 d, and advanced by a decrease from 25 to 3 lux at 112 d. Sexual maturity of ISA Browns was not significantly affected by a change in illuminance at 63 or 112 d, though responses were in the same direction as for Shaver Whites. 4. In both breeds, total feed consumed to 112 d was higher for birds on 3 lux than 25 lux, but lower between 112 d and 140 d when birds on 25 lux underwent rapid sexual development. In both breeds, body weight at 63 d was higher for birds exposed to 3 lux than 25 lux, but body weight gain thereafter was similar for the two light intensities. 5. In both breeds, plasma luteinising hormone (LH) concentration at 63 and 112 d was lower in birds maintained on 3 lux than 25 lux. At 63 and 112 d, transfers from 25 to 3 lux depressed, whereas transfers from 3 to 25 lux at 63 d, but not at 112 d, increased plasma LH. 6. Advances or delays in sexual maturity induced by changes in illuminance were not correlated with differences in feed intake, body weight gain, or with changes in plasma LH. 7. One possible explanation for the inverse relationship between the direction of change in illuminance at 63 and 112 d in pullets exposed to a 10-h photoperiod and the age at which they became sexually mature is that changes in light intensity and/or spectral composition affect the entrainment of the circadian rhythm of photoinducibility, to effect a phase shift in the photoinducible phase and/or the responsiveness of phototransduction pathways.     

Bilateral phacofragmentation in a New Zealand fur seal (Arctocephalus forsteri).

Ophthalmic examination under anesthesia of a 5-yr-old, captive, male New Zealand fur seal (Arctocephalus forsteri) with reduced visual capacity revealed bilateral cataracts. Surgical extraction of the lenses was performed by phacofragmentation. Preoperative mydriasis was unsuccessful using common topical mydriatic agents. Intraoperative intracameral epinephrine 1:10,000 produced minimal pupillary dilation, but excellent dilation was achieved with intracameral epinephrine at 1:1,000. Postoperative uveitis was controlled with oral prednisolone. Postoperative complications included generalized corneal edema persisting for approximately 1 wk and corneal ulceration caused by the lateral canthotomy sutures. Vision was restored in both eyes.     

放牧绵羊瘤胃液挥发性脂肪酸的变化规律及其受蠕虫感染的影响

选用敖汉细毛羊的育成母羊和成年母羊进行了3年试验.第1年试验在同一饲养水平下设对照组、常规驱虫组和缓释胶囊驱虫组;第2年和第3年又在常规饲养和改进饲养2种饲养方案下进行驱虫试验.所有试验羊在以披碱草、羊草和冰草为主的同类草场上放牧,每年进行3次驱虫处理.试验表明:放牧绵羊瘤胃液中挥发性脂肪酸(VFA)浓度随季节呈动态变化.其挥发性脂肪酸总量(TVFA)在青草期内较高;在枯草期内较低.放牧绵羊瘤胃发酵水平较低,特别在冬春季节内瘤胃发酵处于最低水平,发酵质量不高.另外,绵羊瘤胃液pH值随季节变动幅度较小.但发现在枯草期内的瘤胃液pH值高于青草期,特别在冬春季节内较高.蠕虫感染严重的时期内,蠕虫会影响绵羊瘤胃发酵水平,使瘤胃液VFA浓度降低;但常规驱虫法与缓释胶囊驱虫法间差异不显著.改进饲养与常规饲养方案对绵羊瘤胃液挥发性脂肪酸总量无显著影响.     

Protection studies with a globin-enriched protein fraction of Ostertagia ostertagi

The protective capacity of an adult stage Ostertagia ostertagi globin antigen was tested in four vaccination experiments in cattle. In a preliminary experiment, calves were vaccinated three times intraperitoneally with 250 microg globin in Freund's adjuvant and challenged with a trickled infection of 25,000 infective larvae. In three subsequent field studies, calves were vaccinated twice or three times intramuscularly with 80-100 microg globin in Quil A and challenged with a natural gastrointestinal nematode infection on pasture. Higher globin-specific antibody levels were detected in the vaccinated calves than in the control animals in all vaccine trials. In the preliminary experiment, geometric mean cumulative egg counts in the globin group were reduced by 52% and total worm burdens were reduced by 28%, compared to the controls. In the first field trial cumulative faecal egg counts were reduced by 63% in the vaccinated calves. However, the reduction in faecal egg output in these two experiments was not statistically significant and no reduction in faecal egg counts was observed in the vaccinated animals in the two last field trials. In conclusion, vaccination of calves with O. ostertagi globin resulted in highly variable protection levels after challenge infection.     

A novel subgroup among genotypes of equine arteritis virus: genetic comparison of 40 strains

The authors determined partial nucleic sequences of the variable regions of open-reading frame (ORF5) from 151 nucleotide to 668 nucleotide and deduced amino acid sequences of 518 nucleotide respectively of 20 equine arteritis virus (EAV) isolates. About 19 Hungarian and one Austrian EAV strains were subjected to sequence analysis, the further data of 20 EAV strains: six North American and 14 European were obtained from the GenBank. Comparative sequence analysis of the Hungarian EAV strains indicated that among the three variable regions the first has been affected mostly by point mutations. Genetic comparison of the Hungarian strains with other EAV isolates from western Europe and North America (including the Bucyrus reference strain) has been performed on the aforementioned genome region. Besides the already known genetic subgroups of EAV; phylogenetic analysis revealed a novel subgroup comprising mainly Hungarian strains. Compared with the Bucyrus virus, the overall sequence divergencies of the examined Hungarian strains ranged from 81.47 to 90.73% at nucleotide and from 84.88 to 91.86% at amino acid level. Epizootiological studies have shown that the significant part of the EAV strains having been existed in Hungary before and in 2000 belong to this unique cluster (II.D) which was not indicated in former phylogenetic studies. After 2000 new EAV strains emerged in Hungary, one of them causing abortions or neonatal death. The previously dominant 'Hungarian' EAV genotypes were replaced by these new strains belonging to North American and European subgroups (I.A, I.B, II.A, II.B). The anamnesis of these cases revealed connections with persistent virus shedder stallions, those were imported to the country after 2000 or have been infected abroad. One of these Hungarian stallions became the source of abortion storms in Hungarian studs.     

Idiopathic pericarditis and cardiac tamponade in two cows

Idiopathic pericarditis is an uncommon diagnosis in cattle with cardiac tamponade. Two cows were examined for clinical signs of right-sided congestive heart failure, including tachycardia, venous distention, and peripheral edema. Muffled heart sounds were detected in one of the cows. Echocardiography in both cows revealed voluminous anechoic pericardial effusion and compression of the right atrium and right ventricle. Cytologic analysis of the pericardial fluid revealed hemorrhagic inflammation but no evidence of a septic or neoplastic condition such as traumatic reticulopericarditis or lymphoma, respectively. Pericardial drainage and lavage accompanied by treatment with anti-inflammatory drugs were curative in both cows. It is important to differentiate cows with idiopathic pericarditis from cows with more common septic pericarditis because the prognosis for the former disease appears to be good with appropriate treatment.     

The pharmacokinetics of vedaprofen and its enantiomers in dogs after single and multiple dosing

Vedaprofen is a chiral nonsteroidal anti-inflammatory drug that has been developed as a gel formulation for oral administration to dogs and horses. The pharmacokinetics of vedaprofen and its enantiomers were studied in beagle dogs after single (intravenous solution and oral gel) and multiple (oral gel) dosing at a dosage of 0.5 mg/kg body weight. Plasma concentrations of vedaprofen and its enantiomers were analysed by HPLC. The plasma protein binding of vedaprofen was studied by ultrafiltration. The absorption of vedaprofen was rapid (tmax 0.63 +/- 0.14 h) and almost complete after oral administration (bioavailability 86 +/- 7%). The terminal half-lives after intravenous and oral administration, 16.8 +/- 2.2 and 12.7 +/- 1.7 h respectively, were of the same order of magnitude. Enantioselective analysis showed that the R(-) enantiomer predominated in plasma. The change in the plasma time course of the plasma R(-)/S(+) enantiomer concentration ratio over time was similar after single intravenous and oral dosing, with R(-)/S(+) ratios in the AUC of 1.7 +/- 0.5 and 1.9 +/- 0.2 respectively. Plasma protein binding of vedaprofen and its enantiomers was high (> 99.5%). Vedaprofen is absorbed rapidly from the gastrointestinal tract, has a high bioavailability and does not accumulate in plasma in dogs following repeated oral administration.