To identify and characterize abnormalities of iris vasculature in dogs with diabetes mellitus, compared to clinically normal, age-matched control dogs, by means of anterior segment angiography.
10 dogs with naturally occurring diabetes mellitus and 10 age-matched control dogs with no ocular or systemic disease.
The day before iris vasculature abnormality (IVA) assessment, all dogs underwent complete physical and ophthalmic examinations and baseline clinicopathologic analyses. For diabetic dogs, serum fructosamine concentration and a 12-hour blood glucose concentration curve were generated. The next day, all dogs were sedated and anterior segment angiography (following IV injection of indocyanine green [1 mg/kg] and subsequently sodium fluorescein [20 mg/kg]) was performed with a full-spectrum camera and camera adapter system. Group findings were compared, and multiple linear regression analysis was performed to identify potential factor associations with IVAs.
During anterior segment angiography, the arterial, capillary, and venous phases were identified in all dogs. Times to onset of all phases in diabetic dogs were significantly less than those in control dogs. Vascular disruptions within the peripupillary region (evident following sodium fluorescein administration) were common in diabetic dogs. Severity of dye leakage into the iris stroma and aqueous humor was significantly greater in diabetic dogs than in control dogs. Duration of disease, mean blood glucose concentration, and serum fructosamine concentration were significantly associated with IVAs.
CONCLUSIONS AND CLINICAL RELEVANCE
In diabetic dogs, anterior segment angiography revealed IVAs that were not evident in control dogs. The severity of those changes appeared to be associated with disease duration and blood glucose regulation.
OBJECTIVE To evaluate pharmacokinetics of ammonium tetrathiomolybdate (TTM) after IV and oral administration to dogs and effects of TTM administration on trace mineral concentrations.
ANIMALS 8 adult Beagles and Beagle crossbreds (4 sexually intact males and 4 sexually intact females).
PROCEDURES Dogs received TTM (1 mg/kg) IV and orally in a randomized crossover study. Serum molybdenum and copper concentrations were measured via inductively coupled plasma mass spectrometry in samples obtained 0 to 72 hours after administration. Pharmacokinetics was determined via noncompartmental analysis.
RESULTS For IV administration, mean ± SD terminal elimination rate constant, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 4.9 ± 0.6 μg/mL, 30.7 ± 5.4 μg/mL•h, and 27.7 ± 6.8 hours, respectively. For oral administration, mean ± SD terminal elimination rate constant, time to maximum concentration, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 3.0 ± 3.5 hours, 0.2 ± 0.4 μg/mL, 6.5 ± 8.0 μg/mL•h, and 26.8 ± 8.0 hours, respectively. Oral bioavailability was 21 ± 22%. Serum copper concentrations increased significantly after IV and oral administration. Emesis occurred after IV (2 dogs) and oral administration (3 dogs).
CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetics for TTM after a single IV and oral administration was determined for clinically normal dogs. Absorption of TTM after oral administration was variable. Increased serum copper concentrations suggested that TTM mobilized tissue copper. Further studies will be needed to evaluate the potential therapeutic use of TTM in copper-associated chronic hepatitis of dogs.