Objective: To assess inhibitory effects of orally administered anti-inflammatory medications on paracentesis-induced intraocular inflammation in clinically normal cats. Animals: 30 clinically normal domestic shorthair cats. Procedures: Cats were randomly assigned to a control group and 4 treatment groups. Cats in the treatment groups received an anti-inflammatory medication orally once daily at 7 am (acetylsalicylic acid [40.5 mg/cat], meloxicam [0.1 mg/kg], prednisone [5 mg/cat], or prednisolone [5 mg/cat]) for 5 days beginning 2 days before paracentesis-induced breakdown of the blood-aqueous barrier (BAB) and continuing until 2 days after paracentesis. Paracentesis of the anterior chamber was performed in 1 randomly selected eye of each cat. Fluorophotometry was performed in both eyes of each cat immediately before (time 0) and 6, 24, and 48 hours after paracentesis. Results: At 24 and 48 hours after paracentesis, fluorescein concentration in the eye subjected to paracentesis in the cats receiving prednisolone was decreased, compared with that in the control cats. At 48 hours, a decrease in the fluorescein concentration was also apparent in the eye subjected to paracentesis in the cats receiving meloxicam, compared with that in the control cats. There was no evidence of treatment effects for acetylsalicylic acid or prednisone. There was no evidence of treatment effects in eyes not subjected to paracentesis. Conclusions and Clinical Relevance: Orally administered prednisolone and meloxicam significantly decreased intraocular inflammation in clinically normal cats with paracentesis-induced BAB breakdown. Oral administration of prednisolone or meloxicam may be an effective treatment for cats with uveitis.

Objective—To describe the effects of prednisone and acetylsalicylic acid (ASA) on results of thromboelastography in healthy dogs. Animals—16 male mixed-breed dogs. Procedures—Dogs were randomly assigned to 3 treatment groups (4 dogs/group) that received prednisone (median dose, 2.07 mg/kg), ASA (median dose, 0.51 mg/kg), or both drugs, PO, every 24 hours from days 0 through 6. Another group received no treatment (control dogs; n = 4). Thromboelastography variables (reaction time, clotting time, α-angle, maximum amplitude [MA], global clot strength, coagulation index, and percentage of clot lysis at 60 minutes [CL60]) were evaluated in blood samples collected (prior to drug administration in treated dogs) on days 0 (baseline), 2, 4, and 6. Results—Administration of ASA alone did not alter TEG variables. For treatment effect, mean global clot strength was increased in the prednisone and drug combination groups, compared with values for control dogs; MA was also increased in the prednisone and drug combination groups, compared with that of controls. For treatment-by-time effect, median CL60 was increased in the prednisone group on day 6, compared with baseline value in the same dogs and with median CL60 of the control group on day 6. Median CL60 was also increased in the drug combination group on day 6, compared with the baseline value and with that of the control group on day 6. Conclusions and Clinical Relevance—Prednisone administered at approximately 2 mg/kg/d, PO, for 7 days with or without concurrently administered ASA increased clot strength and decreased clot lysis in healthy dogs.

Objective-To clone segments of the canine liver alkaline phosphatase (LALP) and corticosteroidinduced alkaline phosphatase (CIALP) genes and use those clones to determine the tissue source of CIALP, the kinetics of LALP and CIALP mRNA expression for glucocorticoid-treated dogs, and the correlation between LALP and CIALP transcript concentrations and isoenzyme activities. Sample Population-Tissues obtained from 7 dogs treated with prednisone (1 mg/kg, SC, q 24 h) for up to 32 days and 1 untreated (control) dog. Procedure-Gene segments of LALP and CIALP were obtained by reverse transcription-polymerase chain reaction (RT-PCR) assay. The tissue source of CIALP and IALP mRNA was determined by northern blot analysis of tissues from 1 of the glucocorticoidtreated dogs. Hepatic tissues and serum samples were obtained from the 6 remaining glucocorticoidtreated dogs on days 0, 2, 5, 10, and 32 of prednisone treatment, and relative expression of LALP and CIALP mRNA was correlated with LALP and CIALP activity. Results-A 2,246-base pair (bp) segment of canine LALP and a 1,338-bp segment of CIALP were cloned. Northern blot analysis revealed CIALP mRNA expression in hepatic tissues only after glucocorticoid treatment. Kinetics of LALP and CIALP mRNA expression in the liver of glucocorticoid-treated dogs paralleled liver and serum activities of LALP and CIALP. Conclusions and Clinical Relevance-The liver is the most likely source for CIALP in dogs. Analysis of kinetics of serum and hepatic LALP and CIALP mRNA suggests that after glucocorticoid treatment, both are regulated by modification of mRNA transcript concentrations, possibly through differing mechanisms.

Prednisone was given orally to 12 dogs daily for 35 days at an anti-inflammatory dosage (1.1 mg/kg of body weight in divided dose, q 12 h) to study its effect on thyroxine (T4) and triiodothyronine (T3) metabolism. Six of these dogs were surgically thyroidectomized (THX-Pred) and maintained in euthyroid status by daily SC injections of T4 to study peripheral metabolism while receiving prednisone; 6 dogs with intact thyroid gland (Pred) were given prednisone; and 6 additional dogs were given gelatin capsule vehicle as a control group (Ctrl). Baseline T4 concentration after 4 weeks of treatment was not significantly different in dogs of the THX-Pred or Pred group (mean +/- SEM, 2.58 +/- 0.28 or 3.38 +/- 0.58 microgram/dl, respectively) vs dogs of the Ctrl group (2.12 +/- 0.30 microgram/dl). A supranormal response of T4 to thyrotropin was observed in dogs of the Pred group, but the T4 response to thyrotropin-releasing hormone was normal. Baseline T3 concentration in dogs of both steroid-treated groups was significantly (P < 0.05) lower after 2 and 4 weeks of prednisone administration vs pretreatment values, but normalized 2 weeks after prednisone was stopped. Free T3 (FT3) and T4 (FT4) fractions and absolute FT3 and FT, concentrations were not altered by prednisone administration. Reverse T3 (rT3) concentration in vehicle-treated Ctrl dogs (26.6 +/- 3.5 ng/dl) was not different from rT3 concentration in dogs of the THX-Pred (25.7 +/- 4.3 ng/dl) and Pred (28.9 +/- 3.8 ng/dl) groups after 4 weeks of medication. These data indicate that daily oral administration of such anti-inflammatory dose of prednisone for 1 month reduces baseline serum T3 concentration, does not alter serum T4 concentration, and enhances thyroidal sensitivity to thyrotropin.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P < 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P < 0.05) reduced and reserve function was markedly (P < 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.

Flunixin meglumine has been reported to induce gastrointestinal lesions in dogs when administered at therapeutic dosages. We administered flunixin meglumine to dogs daily for 10 days to assess the effect of this drug on the gastrointestinal tract. We also evaluated the possibility of corticosteroid potentiation of gastrointestinal toxicosis by concurrent administration of prednisone to 1 group of dogs. Dogs were monitored for gastrointestinal toxicosis by means of serial endoscopic evaluation, measurement of fecal occult blood, PCV, and total solid concentration, and by physical examination. There were 3 treatment groups of 5 dogs each. Group-1 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM; group-2 dogs were given 4.4 mg of flunixin meglumine/kg daily, in 2 divided doses IM; and group-3 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM plus 1.1 mg of prednisone/kg/d orally, in 2 divided doses. A fourth group of 5 dogs served as a control group. Endoscopically visible gastric mucosal lesions developed in all treated dogs within 4 days of initiating treatment. Lesions first developed in the gastric pylorus and antrum and lesions at these sites were more severe than those observed elsewhere. Dogs treated with flunixin meglumine plus prednisone developed the earliest and most severe lesions; lesion scores in group-2 dogs were higher than those in group-1 dogs. All dogs treated had occult blood in their feces by day 5 and its presence appeared to correlate more closely with endoscopic findings than did physical examination findings or changes in values for PCV or total solids. Deep ulcers were observed in the pylorus of most treated dogs examined at necropsy on day 10. Shallow ulcers and erosions were in the small intestine of group-2 and -3 dogs. Capillary microthrombi, associated with lesions of coagulative necrosis of superficial epithelium, were found in the colonic and small intestinal mucosa of several dogs in groups 2 and 3, and were suggestive of vascular injury. From results of this study, it was concluded that flunixin meglumine, administered at therapeutic doses, induced early gastric mucosal injury in dogs and that concurrent administration of prednisone may have exacerbated the gastrointestinal injury induced by flunixin alone. Endoscopic evaluation and measurement of fecal occult blood appeared to be more sensitive than other methods evaluated for detection of gastrointestinal injury.

OBJECTIVE To determine whether a dose-response relationship exists between short-term oral prednisone administration and common clinicopathologic variables, cardiovascular biomarkers, and systolic arterial blood pressure (SAP) in healthy dogs. ANIMALS 8 healthy Beagles. PROCEDURES Dogs underwent five 5-day experiments (no prednisone treatment [control condition] and prednisone administration at 0.5, 1, 2, and 4 mg/kg, PO, q 24 h), with a 9-day washout period between protocols. Analyses performed before and after treatments included a CBC, serum biochemical analysis, and determination of SAP, fractional excretion of electrolytes, urine protein-to-creatinine ratio, glomerular filtration rate (GFR), serum N-terminal pro B–type natriuretic peptide (NT-proBNP) and plasma cortisol concentrations, and plasma renin activity. Linear mixed-effects modeling was used to compare changes in variables from baseline (day 1 for the same experiment) among treatment conditions. RESULTS Changes in serum glucose concentration and GFR were significantly greater after administration of prednisone at 4 mg/kg than for the control condition. Fractional excretion of sodium was decreased from baseline when dogs received 0.5, 1, or 4 mg of prednisone/kg, compared with results for the control condition. Several expected changes in clinicopathologic values were observed after prednisone administration at any dose. Changes in serum NT-proBNP concentration, plasma renin activity, and SAP did not differ from changes for the control condition at any prednisone dose. CONCLUSIONS AND CLINICAL RELEVANCE Oral prednisone administration did not affect SAP, NT-proBNP concentration, or measures of renin-angiotensin-aldosterone system activation in healthy laboratory-housed dogs but was associated with relative increases in GFR and serum glucose concentration.

OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally administered intermediate-acting glucocorticoids (prednisone) could predispose dogs to progression of heart disease or congestive heart failure. ANIMALS 11 client-owned dogs with allergic dermatitis and 11 matched healthy control dogs. PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO) once daily for 14 consecutive days beginning on day 0 (baseline), followed by a tapering and washout period; control dogs received no treatment. Measurements were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare changes in variables across measurement points and between dog groups. RESULTS Prednisone administration caused no significant changes in serum sodium or potassium concentration, blood glucose concentration, or target echocardiographic variables. The change from baseline in systolic arterial blood pressure at day 7 was significantly greater in prednisone-treated dogs than in control dogs. Expected changes in hematologic and serum biochemical values with prednisone administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline phosphatase and alanine aminotransferase activities) also occurred in the prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that anti-inflammatory doses of orally administered glucocorticoids have the potential to adversely impact cardiac function in dogs by causing an increase in blood pressure and thus increased cardiac afterload.

Objective: To determine the effects of oral prednisone administration with or without ultralow-dose acetylsalicylic acid on coagulation parameters in healthy dogs and to assess intraindividual variation in thromboelastography results. Animals: 14 healthy research dogs and 10 healthy client-owned dogs. Procedures: In a randomized controlled trial, research dogs underwent thromboelastography twice (3 days apart), and intraindividual variation in test results was calculated. Dogs were given prednisone (2 mg/kg/d, PO) plus acetylsalicylic acid (0.5 mg/kg/d, PO) or prednisone (2 mg/kg/d, PO) plus a placebo for 14 days, after which thromboelastography and other tests were repeated. Differences from preadministration (baseline) test results between and within groups were compared. In a separate trial, client-owned dogs also underwent thromboelastography twice 2 days apart to assess intraindividual variation in untreated dogs. Results: Intraindividual variation in thromboelastography results for research dogs was ≤ 10% for maximum amplitude (MA) and α angle. In the research dogs, MA and fibrinogen values significantly increased from baseline, whereas percentage lysis 30 minutes after attainment of the MA as well as antithrombin activity significantly decreased within each group. In the dogs that received prednisone plus a placebo, percentage lysis 60 minutes after attainment of the MA was significantly lower than at baseline. For all parameters for research dogs, there was no difference between groups for change from baseline. Intraindividual variation in findings for client-owned dogs was similar to the variation for research dogs. Conclusions and Clinical Relevance: Prednisone administration resulted in hypercoagulability in healthy dogs as indicated by an increase in MA and plasma fibrinogen concentration and a decrease in antithrombin activity. Concurrent ultralow-dose acetylsalicylic acid use had no effect on measured thromboelastography values. The high intraindividual variation in some thromboelastography parameters may preclude routine use of this technique in clinical practice.

Effects of a single IV administered therapeutic dose of vincristine sulfate on platelet numbers and function were evaluated in 16 clinically normal dogs over the 2 weeks after drug administration. Results were statistically compared with those of a previous control study in which the same 16 dogs were administered saline solution (IV), instead of vincristine. Of the 16 dogs, 8 were orally administered daily immunosuppressive doses of prednisone concurrently throughout the saline-control and vincristine study periods. Platelet numbers and mean platelet volume were measured, using an automated hematology analyzer. Platelet function was evaluated by turbidimetric measurement of platelet aggregation in response to collagen, platelet-activating factor, and adenosine diphosphate (ADP), and by clot retraction (diluted whole-blood method) and buccal mucosa bleeding time. Vincristine had a significant (P < 0.05) effect on circulating platelet numbers. Vincristine induced a transient mild decrease in platelet numbers, followed by a moderate increase in numbers, with peak platelet count observed 8 days after drug administration. Mean platelet volume was not significantly affected by administration of vincristine. Vincristine had no significant effects on platelet aggregation in response to collagen, low or high doses of platelet-activating factor, and a high dose of ADP. The maximal degree of platelet aggregation attained in response to a low dose of ADP was not significantly affected by prior administration of vincristine. The maximal rate of platelet aggregation induced by a low dose of ADP after vincristine administration, however, was significantly (P < 0.05) lower than the rate of aggregation induced by a similar dose of ADP in the previous control study. Vincristine had no significant effects on clot retraction and bleeding time. Prednisone did not significantly affect platelet numbers and function, and did not modify vincristine's effects on the same variables.