Clinical evaluation of a single daily dose of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch

The objective of this retrospective study was to determine the efficacy of a single daily oral dose of phenylpropanolamine (PPA) in the treatment of urethral sphincter mechanism incompetence (USMI) in bitches. Nine bitches diagnosed with USMI were treated with a single daily dose [1.5 mg/kg body weight (BW)] of PPA for at least 1 month. Urethral pressure profiles (UPP) were performed in 7 dogs before treatment and repeated in 4 of them after treatment. Treatment with PPA resulted in long-term continence in 8/9 bitches. One dog did not respond to PPA and was treated surgically later. Recheck UPPs showed a significant increase in maximal urethral closure pressure in the 4 bitches after treatment with PPA compared to before treatment. In conclusion, long-term continence can be achieved in bitches affected with USMI after administration of a single daily dose of PPA (1.5 mg/kg BW).     

Urodynamic and haemodynamic effects of a single oral administration of ephedrine or phenylpropanolamine in continent female dogs

This study investigated the effects of a single oral administration of ephedrine (2 mg/kg) or phenylpropanolamine (PPA) (1.5 mg/kg) on the vesico-urethral and cardiovascular functions in continent female dogs. Urethral pressure profilometry (UPP), arterial blood pressures and heart rate were measured in five control dogs and after single-dose treatment with ephedrine or PPA at T(0), T(2h), T(4h), T(6h), T(12h), T(18h) and T(24h). UPPs were performed under propofol anaesthesia and other measurements were performed on awake dogs. A telemetric urodynamic investigation was performed on three additional dogs for 24 h after the administration of each drug. Urethral pressures increased over 4-6 h and urethral functional lengths increased 2-6h after administration of both drugs. During micturition, a decrease in detrusor pressure coupled with an increase in bladder volume was observed after ephedrine administration and there was also an increase in bladder volume after PPA had been given. With both drugs increased arterial blood pressures at 4-6 h were compensated by a decreased heart rate over 12 h. Urethral function was improved after both ephedrine and PPA, and bladder function also improved during micturition following ephedrine.     

Effects of aspirin dose escalation on platelet function and urinary thromboxane and prostacyclin levels in normal dogs

Established “low” aspirin dosages inconsistently inhibit platelet function in dogs. Higher aspirin dosages consistently inhibit platelet function, but are associated with adverse effects. The objectives of this study were to use an escalation in dosage to determine the lowest aspirin dosage that consistently inhibited platelet function without inhibiting prostacyclin synthesis. Eight dogs were treated with five aspirin dosages: 0.5 mg/kg q24h, 1 mg/kg q24h, 2 mg/kg q24h, 4 mg/kg q24h and 10 mg/kg q12h for 7 days. Utilizing aggregometry and a whole‐blood platelet function analyzer (PFA‐100), platelet function was evaluated before and after treatment. Urine 11‐dehydro‐thromboxane‐B₂ (11‐dTXB₂) and 6‐keto‐prostaglandin‐F_1α (6‐keto‐PGF_1α), were measured. Compared to pretreatment, there were significant post‐treatment decreases in the maximum aggregometry amplitude and increases in the PFA‐100 closure times for all dosages expect 0.5 mg/kg q24h. There was no difference in amplitude or closure time among the 2 mg/kg q24h, 4 mg/kg q24h, and 10 mg/kg q12h dosages. Compared to pretreatment values, there was a significant decrease in urinary 11‐dTXB₂‐to‐creatinine and 6‐keto‐PGF_1α‐to‐creatinine ratios, but there was no dose‐dependent decrease for either metabolite. An aspirin dosage of 2 mg/kg q24h consistently inhibits platelet function without decreasing prostacyclin synthesis significantly more than lower aspirin dosages.     

Influence of acetylsalicylic acid and ketoprofen on canine thyroid function tests

Many factors including drugs can influence thyroid function in humans, rats and dogs. Studies in humans report significant effects of non-steroidal anti-inflammatory agents (NSAIDs) on thyroid function tests, which can lead to misinterpretation of the results and inappropriate therapeutic decisions. As NSAIDs are used more and more frequently in dogs, it is important to know to what extent they can influence results. Eighteen spayed female beagle dogs were randomly assigned to three treatment sequences in a 3 x 3 crossover study design with treatments consisting of acetylsalicylic acid (ASA) (25 mg/kg BW q 12 h), ketoprofen (Keto) (1 mg/kg BW q 24 h) or placebo administered for a 1-week period with a 3-week washout period between treatment periods. Blood samples for determination of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), thyrotropin (TSH), reverse triiodothyronine (rT3), Keto and ASA concentrations were taken during each treatment period on days 0, 1, 3 and 7. During the washout period samples were taken weekly. A significant decrease in TT4 was observed as soon as 24 h after ASA administration, whereas the decrease in TT3 was less pronounced and differed significantly from the placebo only after 1 week of administration. No significant effects were found for free T4 and TSH with ASA administration. No significant effects on thyroid results were found following Keto administration. The results indicate that TT4 can be markedly decreased by ASA therapy and until the results of further studies are available, thyroid function test results should be interpreted cautiously in dogs on NSAIDs therapy.     

Effects of selegiline,phenylpropanolamine, or a combination of both on physiologic and behavioral variables in healthy dogs

OBJECTIVE: To determine effects of selegiline hydrochloride, phenylpropanolamine (PPA), or a combination of both on physiologic and behavioral variables in dogs. ANIMALS: 40 adult hound-type dogs. PROCEDURE: Dogs were assigned to 4 groups. One group received selegiline (1 mg/kg, PO, q 24 h) and PPA (1.1 mg/kg, PO, q 8 h), a second group received selegiline alone, a third group received PPA alone, and a fourth group received neither drug. Dogs were observed 3 times/d throughout the 30-day study (daily during the first week, on alternate days during the next 2 weeks, and again daily during the final week). Observers recorded rectal temperature, pulse, respiratory rate, oscillometric blood pressure, and lead-II ECG and assessed 4 behaviors, using an analogue scale. Variables were compared among treatment groups by use of a 2-factor ANOVA with data categorized into three 10-day treatment periods. A similar comparison was made among treatment groups with data categorized by time of observation (morning, afternoon, or evening) for all study days. RESULTS: Variables did not differ among groups at study initiation. Pulse rate was the only variable that differed significantly among treatment groups during the study. During the first 10 days of treatment, dogs receiving PPA had a lower pulse rate than dogs that did not. Although signs of illness were apparent in a few dogs, illness did not appear to be related to treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Adverse effects were not detected after administration of selegiline, PPA, or a combination of the drugs in healthy dogs.     

Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3'-triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy dogs

OBJECTIVE: To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. ANIMALS: 24 dogs. PROCEDURE: Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. RESULTS: Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.     

Effects of clomipramine hydrochloride on heart rate and rhythm in healthy dogs

OBJECTIVE: To determine the effects of clomipramine hydrochloride on heart rate and rhythm in dogs. ANIMALS: 17 healthy Beagles. PROCEDURES: In experiment 1, 8 dogs received placebo or clomipramine (20 mg/kg of body weight, q 24 h, PO) for 7 days in a 2-way crossover design. In experiment 2, 9 dogs were evaluated for 48 hours before and 24 hours after oral administration of clomipramine (4 or 12 mg/kg) in a 2-way crossover design. Electrocardiogram and heart rate were monitored continuously by use of telemetry. RESULTS: A significant diurnal rhythm in heart rate was detected; minimum values were recorded at night. Administration of 20 mg of clomipramine/kg induced a significant reduction in heart rate, with peak effect achieved approximately 12 hours after dosing. Administration of 4 or 12 mg of clomipramine/kg did not result in significant changes in heart rate. Sinoatrial and second-degree atrioventricular block and ventricular escape beats were observed during periods of slow heart rate in more dogs that received clomipramine (3 to 4 of 8 dogs), compared with dogs that received placebo (1 to 2 of 8 dogs), but this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Short-term administration of clomipramine induced benign cardiovascular effects in dogs rather than the potentially dangerous arrhythmias or tachycardia reported following administration of tricyclic antidepressants to humans. Precautions regarding cardiovascular effects may not be needed for the use of clomipramine in healthy dogs.     

The effects of the loop diuretics furosemide and torasemide on diuresis in dogs and cats

Torasemide is a new loop diuretic that combines the effects of furosemide and spironolactone. There are no reports on the effects of torasemide in cats and dogs. This study compared the diuretic effects of furosemide and torasemide in cats and dogs. Cats with pressure overload cardiac hypertrophy were given oral placebo, torasemide 0.3 mg/kg, or furosemide 1 mg/kg or 3 mg/kg. Control and mitral regurgitation dogs were given oral placebo, torasemide 0.2 mg/kg, and furosemide 2 mg/kg for 7 days. Urine samples were obtained at baseline and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hr after each drug dose. Urine volume and urine Na(+) and K(+) were measured. Both furosemide and torasemide increased urine volume 1 hr after administration. Furosemide caused a dose-dependent increase in urine volume that peaked at 2-3 hr in cats and dogs. The diuretic effect of furosemide disappeared 6 hr after administration, while that of torasemide peaked 2-4 hr after administration and persisted for 12 hr in cats and dogs. In MR dogs, torasemide for 7 days significantly decreased urine potassium excretion. Plasma aldosterone increased with torasemide, whereas there was no change with furosemide. In conclusion, about 1/10 concentration of torasemide was as potent as furosemide and had a longer diuretic effect in cats and dogs. These data suggest that torasemide is useful for treating congestive heart failure or edema in cats and dogs.     

Effects of doxycycline, amoxicillin, cephalexin, and enrofloxacin on hemostasis in healthy dogs

OBJECTIVE: To determine the effects of enteral administration of doxycycline, amoxicillin, cephalexin, and enrofloxacin at therapeutic dosages for a typical duration on hemostatic variables in healthy dogs. ANIMALS: 14 Beagles. PROCEDURE: Doxycycline (10 mg/kg, PO, q 12 h), amoxicillin (30 mg/kg, PO, q 12 h), cephalexin (30 mg/kg, PO, q 12 h), and enrofloxacin (20 mg/kg, PO, q 24 h) were administered in random order to 10 healthy dogs at standard therapeutic dosages for 7 days, with a 7-day washout period between subsequent antimicrobials. In addition, 4 Beagles served as control dogs. Variables were evaluated before and after antimicrobial administration; they included platelet count, Hct, 1-stage prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen concentration, and platelet function. Platelet function was assessed via buccal mucosal bleeding time, aggregation, and a platelet-function analyzer. RESULTS: Administration of all antimicrobials caused a slight prolongation of 1-stage PT and activated PTT and slight decrease in fibrinogen concentration. Cephalexin caused a significant increase in 1-stage PT and activated PTT, amoxicillin caused a significant increase in activated PTT, and enrofloxacin caused a significant decrease in fibrinogen concentration. Platelet count or function did not differ significantly after administration of any antimicrobial. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of commonly used antimicrobials in healthy dogs resulted in minor secondary hemostatic abnormalities, with no change in platelet count or function. Although these changes were clinically irrelevant in healthy dogs, additional studies of the effects of antimicrobial administration on hemostasis in animals with underlying disease processes are warranted.     

The Gastroduodenal Effects of Buffered Aspirin, Carprofen, and Etodolac in Healthy Dogs

Twenty-four healthy mixed-breed dogs were divided into 4 groups. Group 1 received a placebo p.o. q12h, group 2 received an average of 16.5 (15.1-17.8) mg/kg buffered aspirin p.o. q12h, group 3 received an average of 2.2 (2.0-2.4) mg/kg carprofen p.o. q12h, and group 4 received an average of 12.8 (11.7-13.8) mg/kg etodolac p.o. q24h (with a placebo in the PM). All treatments continued for 28 consecutive days. Gastroduodenal endoscopy was performed on days -9, 0, 5, 14, and 28. Multiple gastric biopsies were obtained endoscopically on day -9 to determine each dog's Helicobacter infection status. Four regions in the stomach and 1 region in the proximal duodenum were evaluated endoscopically, and each was assigned a score from 1 to 11. Scores for each region then were summed to give a total score for each endoscopic evaluation. Erosions and submucosal hemorrhages were seen in all dogs receiving aspirin. Only minor gastric lesions were observed in the carprofen, etodolac, and control groups. No adverse clinical signs were noted in any dog given any treatment. Median total score on days 0, 5, 14, and 28, respectively, were as follows: group 1: 5.0, 5.0, 5.0, 5.0; group 2: 5.0, 27.0, 26.0, 27.5; group 3: 5.0, 5.0, 6.0, 5.0, group 4: 5.0, 7.0, 5.0, 5.0. There was no significant difference among dogs receiving carprofen, etodolac, or placebo. The administration of carprofen, etodolac, or placebo to healthy dogs resulted in significantly less gastroduodenal lesion development than in dogs receiving buffered aspirin.     

Effect of oral administration of carprofen on intraocular pressure in normal dogs

The aim of this study was to determine the effect of oral administration of carprofen on intraocular pressure in normal dogs. Twelve young adult beagle dogs were randomly assigned to treatment (n = 6) or control (n = 6) groups. After an 11‐day acclimation period, the treatment group received approximately 2.2 mg/kg carprofen per os every 12 h for 7 days, and the control group received a placebo gel capsule containing no drug per os every 12 h for 7 days. Intraocular pressure (IOP) was measured by a rebound tonometer at three time points per day (8 am, 2 pm, and 8 pm) during the acclimation (days 1–11) and treatment (days 12–18) phases and for 48 h (days 19–20) after the completion of treatment. There was no statistically significant change in IOP for either eye in the dogs receiving oral carprofen during the treatment phase (days 12–18). After day 4, no significant daily IOP changes were seen in control group dogs. Carprofen administered orally every 12 h for 7 days had no effect on IOP in normal beagle dogs. An acclimation period to frequent IOP measurements of at least 5 days is necessary to establish baseline IOP values and minimize possible anxiety‐related effects on IOP measurements.     

Prevention of coccidiosis in domestic dogs and captive coyotes (Canis latrans) with sulfadimethoxine-ormetoprim combination

Sulfadimethoxine-ormetoprim combination was evaluated as a coccidiostat against experimentally induced coccidiosis in young dogs and coyotes (Canis latrans). The animals were experimentally inoculated with 50,000 or 100,000 sporulated oocysts of Isospora ohiohensis (98%) and Isospora canis (2%). In experiment 1, daily treatment for 13 to 23 days with a combination of 27.5 mg of sulfadimethoxine/kg of body weight (BW) and 5.5 mg of ormetoprim/kg of BW admixed to the feed resulted in no significant (P greater than 0.05) difference in fecal oocyst counts between treated and nontreated groups of dogs or coyotes. In experiment 2, treatment with a combination of 55 mg of sulfadimethoxine/kg of BW and 11 mg of ormetoprim/kg of BW for 23 days was 99.8% effective against Isospora spp infections in dogs. Significantly (P less than 0.05) fewer oocysts were present in feces of treated dogs than were present in feces of nontreated dogs from first passage of oocysts at day 4 to the end of the patent period at days 19 to 21. After the 2nd week of treatment, BW of treated dogs were significantly greater (P less than 0.05) than BW of nontreated dogs. Evidence of drug toxicity was not observed clinically or by serum chemical analyses.     

Safety of oral robenacoxib in the cat

The safety of robenacoxib, a nonsteroidal anti-inflammatory drug with high selectivity for inhibition of the cyclooxygenase (COX)-2 isoform of COX, was investigated in the cat in two randomized, blinded, placebo-controlled, parallel-group studies. Robenacoxib was administered orally to healthy young domestic short-hair cats at dosages of 0 (placebo), 5 and 10 mg/kg once daily for 28 days (study 1) and at 0 (placebo), 2, 6 and 10 mg/kg twice daily for 42 days (study 2). The recommended minimum dosage for robenacoxib tablets in cats is 1 mg/kg once daily (range 1-2.4 mg/kg). Relative to placebo treatment, no toxicologically significant effects of robenacoxib were recorded in either study, based on general observations of health, haematological and clinical chemistry variables and urinalyses in life, and by post mortem organ weight, gross pathology and histopathology assessments. Pharmacokinetic-pharmacodynamic simulations indicated that all dosages of robenacoxib were associated with marked inhibition of COX-2 at peak effect (median I(max) 97.8-99.4% inhibition) with lesser inhibition of COX-1 (median I(max) 26.8-58.3% inhibition). Inhibition of the COXs was short lasting, with >10% median inhibition persisting for 4.0 h for COX-2 and 1.5 h for COX-1. These levels of inhibition of COX-1 and COX-2 twice daily with robenacoxib were not associated with any detectable toxicity, suggesting that, as previously described in dogs, the high safety index of robenacoxib in cats may be related to a combination of its high COX-2 selectivity and short residence time in the central compartment.     

Plasma and urine concentrations of marbofloxacin following single subcutaneous administration to cats

The pharmacokinetic properties of marbofoxacin, a third generation fluoroquinolone, were investigated in 12 healthy adult cats after single subcutaneous (SC) administration of 2 mg/kg BW (Part I, n=8 cats) and 4 mg/kg BW (Part II, n=4 cats). In each part of the study blood and urine samples were collected before treatment and thereafter for 5 days. The plasma and urine concentrations of marbofloxacin were determined by HPLC with UV detection. Pharmacokinetic calculations were performed for each treated animal using an open one-compartment-model with first-order elimination after SC dosing. Marbofloxacin in plasma (means): Maximum concentrations (Cmax) of about 1.2 and 3.0 microg/ml were measured 2.3 and 4 hours (tmax) after dosing of 2 and 4 mg/kg BW, respectively. Elimination from the body was low with a total clearance (Cl/F) of approximately 0.1 l/h/kg for both dosages. The half-life (t 1/2) for this process was calculated with 8-10 hours. AUC increased almost proportional when doubling the dose, i.e., 19.77 +/- 6.25 microg * h/ml (2 mg/kg BW) and 51.26 +/- 11.83 microg * h/ml (4 mg/kg BW). Plasma kinetics measured were in accordance with data from literature. Marbofloxacin in urine (means): Maximum drug concentrations were detected 4 and 8 hours after dosing with 70 microg/ml (2 mg/kg BW) and 160 microg/ml (4 mg/kg BW), respectively. Inhibitory effects of the urinary matrix on the antimicrobial activity of the drug were taken into account when performing PK/PD calculations. However, a concentration-dependent bactericidal activity (Cmax/MIC > 8-10) which is claimed for fluoroquinolones was sufficiently met with focus on Escherichia (E.) coli (MIC90 0.5 microg/ml). In the same matrix a threshold value of 1.0 microg/ml was undercut 82 and 116 hours after SC dosing, respectively. Hence, a time-dependent bacteria killing kinetic (T > MIC) which may be of relevance for some Gram-positive germs like Staphylococcus spp. (MIC90 1.0 microg/ml) should be covered, too.     

Phenytoin sodium as a treatment for ventricular dysrhythmia in horses

Five adult horses with ventricular extra systoles (VES) and 2 with ventricular tachycardia (VT) refractory to treatment with rest, anti-inflammatory drugs, lidocaine, or procainamide were treated with phenytoin sodium p.o. q12h. The starting dosage of phenytoin was 20 or 22 mg/kg body weight (BW) q12h, and the maintenance dosage varied from 8 to 17 mg/kg BW q12h. The mean +/- standard deviation therapeutic blood concentration of total phenytoin was 8.8 +/- 2.1 mg/L, and the mean concentration of free phenytoin of 2.5 +/- 0.5 mg/L was relatively constant at a range of 24 to 29% of the total phenytoin concentration. In all horses, both VES and VT were abolished after treatment with phenytoin. On the basis of the results of this clinical study, the authors propose an initial dose of 20 mg/kg BW q12h for the first 3 or 4 dosages, followed by a maintenance dose of 10 to 15 mg/kg BW q12h. Phenytoin plasma concentrations should be monitored during therapy. High plasma concentrations were associated with adverse effects such as recumbency and excitement. In this study, which included a limited number of diverse patients, phenytoin sodium appeared to be an inexpensive and effective treatment for persistent VES or VT in cases where conventional treatment had failed.     

The safety of dirlotapide in dogs

The safety of dirlotapide in dogs was evaluated in two studies with parallel designs. In an acute tolerance study, 24 beagles (six dogs per treatment) were treated orally once daily for 14 days with placebo or dirlotapide at 2.5, 5.0, or 10.0 mg/kg/day. In a margin-of-safety study, 38 overweight, neutered beagles were treated orally once daily for 3 months with dirlotapide at doses up to 0.5 mg/kg/day (six dogs), 1.5 mg/kg/day (12 dogs) and 2.5 mg/kg/day (six dogs). Control dogs received placebo at 0.3 mL/kg/day (10 dogs) and 0.5 mL/kg/day (four dogs). Results were similar for both studies, and no serious adverse events were observed. Dirlotapide was clinically well-tolerated in dogs at dosages up to 10 mg/kg/day for 14 days and 2.5 mg/kg/day for 3 months. Dirlotapide produced the expected decrease in food intake and body weight (up to 20–40%) without ill effects. Clinical, pathologic, and histopathologic findings were reversible and consistent with suppression of food intake and rapid weight loss produced by elevated dirlotapide dosages. In both studies, sporadic emesis and loose stools were observed in both placebo and dirlotapide-treated dogs. Incidence of emesis generally increased with dose and decreased with treatment time. Elevations in hepatic transaminase activity were seen in dogs treated with more than 1.5 mg/kg dirlotapide daily, but were not associated with clinical signs or microscopic evidence of hepatic degeneration or necrosis.     

Effect of deracoxib,a new COX-2 inhibitor,on the prevention of lameness induced by chemical synovitis in dogs

Twenty-four healthy, mixed-breed hound-type dogs were evenly and randomly assigned to a placebo control group, one of four dosages of deracoxib (0.3, 1, 3, or 10 mg/kg), or carprofen (2.2 mg/kg). Oral dosing of placebo, carprofen, or deracoxib was done 30 minutes before intraarticular injection of urate crystal suspension for induction of synovitis. Ground reaction forces, subjective clinical lameness scores, pain, joint effusion, and quantitative pain threshold responses were measured in a blinded fashion before induction of synovitis and 2, 4, 6, 8, 12, and 24 hours after injection. The medium and high dosages of deracoxib were effective in preventing lameness and pain associated with synovitis. Carprofen was also somewhat effective in attenuating the severity of urate-induced synovitis but to a lesser degree than the medium dose of deracoxib. Preemptive deracoxib treatment at dosages as low as 1 mg/kg reduced lameness and pain of synovitis associated with intraarticular administration of urate crystals.     

Designing a treatment protocol with voriconazole to eliminate Aspergillus fumigatus from experimentally inoculated pigeons

To investigate the efficacy of voriconazole for the treatment of aspergillosis, three groups of six racing pigeons (Columba livia domestica) were inoculated in the apical part of the right lung with 2 × 10⁷ conidia of an avian derived Aspergillus fumigatus strain. The minimal inhibitory concentration of voriconazole for this strain was 0.25 μg/ml. In two groups, voriconazole treatment was started upon appearance of the first clinical signs and continued for fourteen days. The third group was sham treated. The voriconazole-treated pigeons received voriconazole orally at a dose of 10 mg/kg body weight (BW) q12h (group 1) or 20 mg/kg BW q24h (group 2). Sixteen days post-inoculation all surviving pigeons were euthanized. Weight loss, clinical scores, daily mortality, lesions at necropsy and isolation of A. fumigatus were compared between all groups. In both voriconazole-treated groups, a significant reduction in clinical signs and lesions was observed. Administering voriconazole at 10 mg/kg BW q12h eliminated A. fumigatus and administering voriconazole at 20 mg/kg BW q24h reduced A. fumigatus isolation rates. Mild histological liver abnormalities were found in group 1 (10 mg/kg BW q12h), while mild histological as well as macroscopic liver abnormalities were found in group 2 (20 mg/kg BW q24h).In conclusion, voriconazole at 10 mg/kg BW q12h in pigeons reduces clinical signs and eliminates A. fumigatus in racing pigeons experimentally infected with A. fumigatus.     

Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs

OBJECTIVE: To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs. ANIMALS: 8 client-owned dogs with clinical signs of osteoarthritis. PROCEDURES: Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations. RESULTS: Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.     

Evaluation of Polysulfated Glycosaminoglycan for the Treatment of Hip Dysplasia in Dogs

A double-blinded, controlled clinical study was performed to compare the response of adult dogs affected with hip dysplasia to a placebo and three different dosages of polysulfated glycosaminoglycan (PSGAG): 2.2 mg/kg, 4.4 mg/kg, and 8.8 mg/kg. Dogs were randomly assigned to treatment groups. The drug was administered intramuscularly every 3 to 5 days for a total of eight injections. Response to treatment was analyzed based on changes in lameness, range of motion (ROM), and pain on manipulation of the hip joints. Evaluation for adverse reactions included complete blood cell (CBC) count, blood urea nitrogen (BUN), creatinine, and physical examination. Data were collected on a total of 111 dogs. Eighty-four met all criteria for inclusion in the study. Dogs that were given 4.4 mg/kg of PSGAG showed the greatest improvement in orthopedic scores, whereas dogs in the placebo group showed the smallest improvement; however, the differences in clinical improvement between the four treatment groups were not statistically significant. No local or systemic adverse reactions related to the drug were observed.