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.     

The influence of high-nitrogen forages on the voluntary feed intake of sheep

The objective of this research was to examine the effect of high concentrations of nonprotein nitrogen (NPN) on the voluntary food intake of sheep fed high-quality grasses. Wether lambs (n = 6 per treatment) were fed dried switchgrass (Panicum virgatum L.; Exp. 1) or dried tall fescue (Festuca arundinacea Schreb.; Exp. 2). In both experiments, urea was added to the dried forage at 0 (control), 12, or 24 g of N/kg of DM to increase the NPN concentration. Acid detergent fiber concentrations were 305 g/kg of DM in both experiments, although DM digestibility was 663 and 618 g/ kg of DM in Exp. 1 and Exp. 2, respectively. Voluntary feed intake of the control forage was 28.2 and 19.1 g/ kg of BW in Exp. 1 and Exp. 2, respectively, and decreased for the high-urea treatments to 25.2 and 16.2 g/kg of BW in Exp. 1 (P = 0.07) and Exp 2 (P = 0.03), respectively. Total feed N concentrations increased from 29.5 g to 45.7 g of N/kg of DM in Exp. 1 (P < 0.01) and from 28.4 to 55.9 g of N/kg of DM in Exp. 2 (P < 0.01). Nonprotein N concentrations increased from 28.3 to 53.8% of the total N in switchgrass diets (Exp. 1; P < 0.01), and from 26.4 to 64.0% in tall fescue diets (Exp. 2; P < 0.01). Plasma urea concentrations of the lambs increased from 3.1 to 6.6 mM (Exp. 1; P < 0.01) and from 2.9 to 5.8 mM (Exp. 2; P < 0.01) as the amount of urea added to the diets increased. These changes resulted in an increase in plasma osmolality from 298 to 307 mOsm/kg (Exp. 1; P = 0.04), and from 299 to 307 mOsm/kg (Exp. 2; P = 0.06). Increasing feed N and NPN concentrations through the addition of urea caused a significant decrease in the voluntary feed intake of sheep fed tall fescue and switchgrass. These responses showed no significant cause-and-effect relationship between voluntary feed intake, plasma urea concentrations, and plasma osmolality.     

Bilateral mandibular dentigerous cysts in a dog

Cysts in the dental cavities of dogs are rare. This report documents the case of a young boxer that was referred after having had treatment for bilateral oral swellings. Dentigerous cysts were tentatively diagnosed. Surgery was performed to aspirate the fluid and remove the first premolars, which were positioned in the cysts. Histopathological examination of tissue collected during the surgical procedure confirmed the diagnosis.     

In vitro inhibition of Eimeria tenella invasion by indigenous chicken Lactobacillus species

The aim of this study was to determine the effects of indigenous chicken Lactobacillus species isolates from different parts of the gastrointestinal tract on Eimeria tenella invasion in vitro and to characterise the nature of inhibition, if any. The effects of competitive exclusion, steric interference and bacterial extracellular factors on E. tenella invasion were examined in an MDBK cell model. Several Lactobacillus species were initially isolated from chickens and identified by biochemical characteristics and 16S-rRNA. All Lactobacillus species isolates tested, significantly inhibited E. tenella invasion. Steric interference did not affect parasite invasion. Extracellular metabolic factors secreted by Lactobacillus species isolates into the surrounding media were shown to inhibit parasite invasion and these factors appeared to be heat stable. These results show that the natural microflora of poultry can provide a source of E. tenella-inhibiting Lactobacillus species in vitro, and thus may contribute to the control of Eimeria infection.     

Serum insulin concentrations in horses with equine Cushing's syndrome: response to a cortisol inhibitor and prognostic value

REASONS FOR PERFORMING STUDY: Serum insulin concentration and its use as a prognostic indicator in horses with equine Cushing's syndrome (ECS) have been poorly documented. OBJECTIVES: To examine daily insulin variations in horses with ECS and the effect of treatment using trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Further, we aimed to examine the relationship between baseline serum insulin concentration and survival in horses with ECS. METHODS: Basal serum insulin concentrations were measured in 20 confirmed ECS cases by taking blood at regular 4 h intervals for 24 h (1200, 1600, 2000, 2400, 0400 and 0800 h) before treatment (Day 0) and 10 days, and 30 days and 1-2 years after the onset of trilostane therapy. The temporal pattern of insulin was analysed using a linear mixed model approach, and the prognostic value of measurements on Day 0 assessed using receiver-operating characteristic analysis. RESULTS: Horses with ECS showed a diurnal pattern of serum insulin concentration, highest value at 1200 h, and this pattern was not altered by treatment with trilostane. Furthermore, despite a mild increase of serum insulin concentrations after 10 days of trilostane therapy, insulin concentration was unaffected in the long-term. Low serum insulin concentrations at the beginning of the trial were significantly associated with improved survival to 1-2 years. The 1200 h sampling before treatment had the highest prognostic value for prediction of survival with a sensitivity and specificity of at least 90% for serum insulin at < 62 and > 188 microu/ml to predict survival and nonsurvival, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Insulin is a useful prognostic indicator for ECS, but potentially large variations can occur throughout a 24 h period, indicating a single sample may not be representative. Serum insulin concentration did not increase over 1-2 years in horses receiving trilostane therapy.     

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.     

Retrospective study of bacterial infective arthritis in 31 dogs

OBJECTIVES: To characterise the presenting signs and pathological changes of canine bacterial infective arthritis in 31 dogs, and to document the response to different treatment regimens. Risk factors that may predispose joints to bacterial infective arthritis and influence the success of treatment were also investigated. METHODS: A retrospective review of cases of bacterial infective arthritis that were presented to three university veterinary referral hospitals over a five-year period (January 1997 to January 2002) was performed. RESULTS: The elbow joint (38 per cent) and stifle joint (44 per cent) were most commonly affected. Radiographic changes consistent with pre-existing osteoarthritis were identified in 14 joints, which had no history of previous surgery (articular or periarticular) or penetrating wound. No significant difference (P = 0.78) was identified between the outcome of combined surgical and medical management, and medical management alone. There were trends for poorer outcomes with increased bodyweight of the dog, longer duration of lameness and a higher nucleated cell count of the affected joint fluid at presentation. The overall infection rate for articular surgical procedures at one institution was 1-3 per cent. CLINICAL SIGNIFICANCE: Medical and/or surgical management were usually successful in resolving infection (94 per cent). However, they were frequently unsuccessful in restoring full joint function; this may in part have been due to the nature of the underlying joint