OBJECTIVE To determine the pharmacokinetics of florfenicol, terbinafine, and betamethasone acetate after topical application to canine auricular skin and the influence of synthetic canine cerumen on pharmacokinetics. SAMPLE Auricular skin from 6 euthanized shelter dogs (3 females and 3 neutered males with no visible signs of otitis externa). PROCEDURES Skin adjacent to the external opening of the ear canal was collected and prepared for use in a 2-compartment flow-through diffusion cell system to evaluate penetration of an otic gel containing florfenicol, terbinafine, and betamethasone acetate over a 24-hour period. Radiolabeled 14C-terbinafine hydrochloride and 3H-betamethasone acetate were added to the gel to determine dermal penetration and distribution. Florfenicol absorption was determined by use of high-performance liquid chromatography–UV detection. Additionally, the effect of synthetic canine cerumen on the pharmacokinetics of all compounds was evaluated. RESULTS During the 24-hour experiment, mean ± SD percentage absorption without the presence of synthetic canine cerumen was 0.28 ± 0.09% for 3H-betamethasone acetate, 0.06 ± 0.06% for florfenicol, and 0.06 ± 0.02% for 14C-terbinafine hydrochloride. Absorption profiles revealed no impact of synthetic canine cerumen on skin absorption for all 3 active compounds in the gel or on skin distribution of 3H-betamethasone acetate and 14C-terbinafine hydrochloride. CONCLUSIONS AND CLINICAL RELEVANCE 3H-betamethasone acetate, 14C-terbinafine hydrochloride, and florfenicol were all absorbed in vitro through healthy auricular skin specimens within the first 24 hours after topical application. Synthetic canine cerumen had no impact on dermal absorption in vitro, but it may serve as a temporary reservoir that prolongs the release of topical drugs.

Phorbol myristate acetate (PMA), which induces acute pulmonary injury in mammals, induced acute airsacculitis in turkeys after intra-airsac inoculation of 0.1 mg/kg. Grossly, air sacs contained multifocal to diffuse hemorrhage and edema at postinoculation hours (PIH) 3 and 6. Microscopically, there was multifocal congestion and small thrombocyte aggregates within small blood vessels by PIH 0.5, with a few vessels containing small numbers of marginating heterophils. By PIH 1.5, thrombocyte aggregates were larger and more numerous, and moderate numbers of heterophils were located perivascularly. Erythrocytes and proteinaceous fluid were in air sac interstitium. By PIH 3 and 6, hemorrhage and exudation of proteinaceous fluid had increased, in some instances severely distending the air sac. Ultrastructurally, changes resulting from PMA-induced injury were thrombocyte aggregation and degeneration, air sac epithelial cell vacuolation with separation of interdigitating cell processes, and endothelial cell vacuolar degeneration with loss of vascular integrity. Air sac lavage fluids had mildly increased total cell counts by PIH 1.5, but values returned to baseline by the end of the experiment, indicating lack of cell exudation into the air sac lumen. Circulating leukocyte changes included transient lymphopenia at PIH 3 and marked heterophilia at PIH 6. These results indicate that thrombocytes and/or heterophils are central to the pathogenesis of injury induced in air sacs by PMA and that the air sac responds differently to PMA than to pathogenic bacteria.

Eight mature horses with no prior signs of joint disease or history of intra-articular therapy were treated with 8 weekly intra-articular injections of methylprednisolone acetate. Treatments were given at a dose of 120 mg/joint into the right radiocarpal and intercarpal joints, with the left joints as untreated controls. Articular cartilage samples were obtained at necropsy 1, 4, and 8 weeks after the last injection. Compared with controls, cartilage from injected joints had loss of hematoxylin basophilia and decreased intensity of staining in safranin O fast green dye. Chondrocyte necrosis and hypocellularity were observed in all samples of cartilage from treated joints. Proteoglycan content and its rate of synthesis were reduced. There was a progressive loss of proteoglycan content, whereas proteoglycan synthesis increased somewhat 4 and 8 weeks after treatment. Collagen content was unchanged, but its rate of synthesis was markedly inhibited. Collagen synthesis did not recover, but remained decreased at 5 to 15% of the values from untreated cartilage. Water percentage was increased, but fibronectin content was not significantly different. A single injection of methylprednisolone acetate was also given into the right metacarpophalangeal joints of 3 of the 8 horses in this group, with the left joints serving as untreated controls. Sixteen weeks after the treatment, cartilage of the treated joints had a loss of histochemical staining and proteoglycan content was reduced to 50% of control values. The mean rate of proteoglycan synthesis and mean fibronectin content were increased, but the differences were not statistically significant (P greater than 0.05). Other variables were essentially unchanged. For control studies, the right carpal joints of 2 additional horses were injected with the drug suspension vehicle. All measurements, compared with those of samples from untreated joints, were unchanged. On the basis of our findings, we concluded that the effects on cartilage of intra-articular injections of methylprednisolone acetate were not ameliorated at 8 weeks after 8 weekly injections or 16 weeks after a single injection. Cartilage remained biochemically and metabolically impaired.

OBJECTIVE To compare the effects of 3 equimolar concentrations of methylprednisolone acetate (MPA), triamcinolone acetonide (TA), and isoflupredone acetate (IPA) on equine articular tissue cocultures in an inflammatory environment. SAMPLE Synovial and osteochondral explants from the femoropatellar joints of 6 equine cadavers (age, 2 to 11 years) without evidence of musculoskeletal disease. PROCEDURES From each cadaver, synovial and osteochondral explants were harvested from 1 femoropatellar joint to create cocultures. Cocultures were incubated for 96 hours with (positive control) or without (negative control) interleukin (IL)-1β (10 ng/mL) or with IL-1β and MPA, TA, or IPA at a concentration of 10(−4), 10(−7), or 10(−10)M. Culture medium samples were collected from each coculture after 48 and 96 hours of incubation. Concentrations of prostaglandin E2, matrix metalloproteinase-13, lactate dehydrogenase, and glycosaminoglycan were determined and compared among treatments at each time. RESULTS In general, low concentrations (10(−7) and 10(−10)M) of MPA, TA, and IPA mitigated the inflammatory and catabolic (as determined by prostaglandin E2 and matrix metalloproteinase-13 quantification, respectively) effects of IL-1β in cocultures to a greater extent than the high (10(−4)M) concentration. Mean culture medium lactate dehydrogenase concentration for the 10(−4)M IPA treatment was significantly greater than that for the positive control at both times, which was suggestive of cytotoxicosis. Mean culture medium glycosaminoglycan concentration did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the in vitro effects of IPA and MPA were similar to those of TA at clinically relevant concentrations (10(−7) and 10(−10)M).

Objective: To evaluate the effects of 4.7-mg deslorelin acetate implants on egg production and plasma concentrations of 17β-estradiol and androstenedione in Japanese quail (Coturnix coturnix japonica) over 180 days and assess safety of the implants in quail via gross and histologic examination. Animals: 20 female Japanese quail. Procedures: Following a 7-day period of consistent egg laying, quail were anesthetized and received a 4.7-mg deslorelin implant (treatment group; n = 10) or identical placebo implant (control group; 10) SC between the scapulae. Egg production was monitored daily. Plasma concentrations of 17β-estradiol and androstenedione were measured on days 0 (immediately prior to implant injection), 14, 29, 62, 90, 120, 150, and 180 via radioimmunoassay. Birds were weighed periodically and euthanized at day 180 for complete necropsy. Results: Egg production was significantly decreased in the treatment group, compared with the control group, from 2 to 12 weeks after implant injection. Egg production ceased in 6 of 10 quail in the treatment group (mean duration of cessation, 70 days). Plasma androstenedione and 17β-estradiol concentrations were significantly lower on day 29 in the treatment group than in the control group. Plama androstenedione and 17β-estradiol concentrations were significantly lower on day 29 in the treatment group then in the control group. Conclusions and Clinical Relevance: 4.7-mg deslorelin acetate implants reversibly decreased egg laying for approximately 70 days in most of the Japanese quail evaluated. Further studies evaluating implants containing different concentrations of the drug are needed in quail and other avian species.

Objective-To compare inhibitory effects of topically applied 1% prednisolone acetate suspension, 0.03% flurbiprofen solution, 0.1% dexamethasone suspension, and 0.1% diclofenac solution on paracentesis-induced blood-aqueous barrier breakdown in cats. Animals-9 healthy cats. Procedures-Paracentesis of the anterior chamber was performed in both eyes of each cat. One eye of each cat was treated with a topically administered anti-inflammatory medication (1% prednisolone [n = 7 cats], 0.03% flurbiprofen [7], 0.1% dexamethasone [9], or 0.1% diclofenac [8]) immediately following paracentesis and at 6, 10, and 24 hours after paracentesis. The contralateral untreated eye served as the control eye. Each cat had a 6-day washout period between experimental drugs. Breakdown of the blood-aqueous barrier was quantified by use of laser flaremetry. Results-Topical administration of 1% prednisolone significantly reduced aqueous humor flare at 4, 8, and 26 hours after paracentesis. Topical administration of 0.1% diclofenac significantly reduced aqueous humor flare at 8 and 26 hours after paracentesis. Topical administration of 0.1% dexamethasone and 0.03% flurbiprofen did not significantly decrease flare at any time point. There were significant differences in intraocular pressures between NSAID-treated eyes and untreated contralateral eyes. Conclusions and Clinical Relevance-Topical administration of 1% prednisolone and 0.1% diclofenac significantly reduced intraocular inflammation in cats with paracentesis-induced uveitis. Topical administration of 1% prednisolone or 0.1% diclofenac may be appropriate choices when treating cats with anterior uveitis. Topical administration of diclofenac and flurbiprofen should be used with caution in cats with a history of ocular hypertension.

Health and ruminal variables were intensively measured during adaptation to grain-based diets in 6 beef cattle with fistulated rumens. The cows had been maintained on prairie grass hay-supplemented diets, and were converted to a grain-based finishing ration by feeding each successive diet (diets 1-4, respectively) for a period of 7 days. Each cow was evaluated and samples were obtained 3 times each day for the first 5 days that each diet was fed. Health variables monitored were rectal temperature, pulse, respiratory and rumen motility rates, fecal consistency, demeanor, blood pH, and blood glucose and L(+) lactate concentrations. Ruminal variables monitored were pH and glucose, DL-lactate, and volatile fatty acid concentrations of rumen contents. Data were analyzed by use of a multivariate ANOVA. We determined that most of the health variables were within reference rang limits throughout the adaptation period; however, analysis of pulse and respiratory rates indicated that diets 2 and 4 were stressful. Although blood pH continually decreased during feeding of the 4 diets (7.38 to 7.30), blood L(+) lactate and glucose concentrations had large increases only within diet 4. The pH of ruminal contents decreased progressively from 6.8 to 5.3. Rumen glucose concentration was low (< 1 micromole/ml), except with diet 4 in which values were 8 times higher than for other diets. By the end of the study, the ruminal contents of all animals were acidic (pH < 5.5), and, on the basis of higher than background amounts of ruminal glucose and DL-lactate, it was determined that rumen microbial equilibrium had not yet been achieved. Analysis of results of this study suggested that ruminal imbalance could be evaluated by monitoring pulse and respiratory rates, blood pH, and blood glucose concentrations. Assessment of the rumen alone could be accomplished by monitoring the variables of rumen pH, rumen glucose, and DL-lactate concentrations. Respiratory rate, blood and rumen content pH, and blood L(+) lactate concentrations were significantly (P < 0.001) affected by time after feeding.

Disinfection is key for controlling microbial contamination and ensuring the safe production of milk and dairy products. In this study, we developed a new disinfection method using quaternary ammonium surfactant N-dodecyl-2-(pyridin-1-yl) acetamide chloride as the main component to form a bactericidal complex with either chlorhexidine acetate or glutaraldehyde, and we evaluated the bactericidal effects, safety, and clinical application value of the compound disinfectants. An in vivo acute oral toxicity assay in mice showed an LD50 > 5000 mg/kg body weight without abnormality in pathological tissue sections. Comparison with commercially available products also showed that they have outstanding bactericidal effects. Clinical trials proved that the compound disinfectants have excellent bactericidal effects on the air and ground of the dairy farm and on the skin of cattle, especially in a dairy farm environment. Our findings confirm that the new compound disinfectants have excellent bactericidal performance and are safe to use as disinfectants to prevent mastitis and contamination of the cattle farm environment.

OBJECTIVE To evaluate and compare regulation of diabetes mellitus (DM) in dogs with cataracts and well-controlled DM that received an ophthalmic preparation of prednisolone acetate versus diclofenac sodium. ANIMALS 22 client-owned dogs with cataracts and well-controlled DM. PROCEDURES A prospective, randomized, double-masked, experimental study was conducted. On days 0 and 32, serum fructosamine concentrations (SFCs), clinical scores, and body weights were determined. Dogs were assigned to receive a topically administered ophthalmic preparation of either prednisolone acetate 1% or diclofenac sodium 0.1% in each eye 4 times daily for 28 days. Data analysis was conducted with generalized linear mixed models. RESULTS Findings indicated no meaningful differences in SFCs, clinical scores, or body weights between the treatment groups on days 0 or 32. Clinical score on day 0 was positively associated with SFC, as indicated by the corresponding rate of change such that each 1 -unit increase in clinical score was associated with an approximately 45.6 ± 9.4 μmol/L increase in SFC. In addition, the least squares mean ± SEM SFC was higher in spayed females (539.20 ± 19.23 μmol/L; n = 12) than in castrated males (458.83 ± 23.70 μmol/L; 8) but did not substantially differ between sexually intact males (446.27 ± 49.72 μmol/L; 2) and spayed females or castrated males regardless of the treatment group assigned. CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated no evidence for any differential effect on DM regulation (assessed on the basis of SFCs, clinical scores, and body weights) in dogs treated topically with an ophthalmic preparation of prednisolone versus an ophthalmic preparation of diclofenac. Additional research investigating plasma concentrations of topically applied ophthalmic glucocorticoid medications is warranted.

The study of alterations of some hematological parameters in a experimentally induced lead toxicosis were carried out on a total of 15 (15 days old) male weaning Long- Evans (ICDDRB strain) rats. The rats were randomly divided in to three equal groups, each consisting of fiverats. Rats of group A were kept as control (without giving any treatment), group B received lead acetate alone @ 6 mg/ml drinking water and group C receivedlead acetate @ 6 mg/ml plus whole milk (Star ship®) 150 mg/ml drinking water. The result showed a most significantly (p< 0.01) decreased TEC, TLC and Hb%observed on day 56 in group B but in group C, these counts decreased significantly (p< 0.05) on days 56 of experiment. From the study, it was concluded that treatment with lead acetate at low doses has harmfuleffects on experimental animals including hematological alterations.