Objective—To evaluate the pharmacokinetics of pentoxifylline
(PTX) and its 5-hydroxyhexyl-metabolite,
metabolite 1 (M1), in dogs after IV administration of a
single dose and oral administration of multiple doses.
Procedure—A crossover study design was used so
that each of the dogs received all treatments in random
order. A drug-free period of 5 days was allowed
between treatments. Treatments included IV administration
of a single dose of PTX (15 mg/kg of body
weight), oral administration of PTX with food at a
dosage of 15 mg/kg (q 8 h) for 5 days, and oral administration
of PTX without food at a dosage of 15 mg/kg
(q 8 h) for 5 days. Blood samples were taken at 0.25,
0.5, 1, 1.5, 2, 2.5, and 3 hours after the first and last
dose of PTX was administered PO, and at 5, 10, 20, 40,
80, and 160 minutes after PTX was administered IV.
Results—PTX was rapidly absorbed and eliminated
after oral administration. Mean bioavailability after
oral administration ranged from 15 to 32% among
treatment groups and was not affected by the presence
of food. Higher plasma PTX concentrations and
apparent bioavailability were observed after oral
administration of the first dose, compared with the
last dose during the 5-day treatment regimens.
Conclusions and Clinical Relevance—In dogs, oral
administration of 15 mg of PTX/kg results in plasma
concentrations similar to those produced by therapeutic
doses in humans, and a three-times-a-day dosing
regimen is the most appropriate. (Am J Vet Res 2000;61:631–637)
Objective—To quantify angular excursions; net joint
moments; and powers across the stifle, tarsal, and
metatarsophalangeal (MTP) joints in Labrador
Retrievers and Greyhounds and investigate differences
in joint mechanics between these 2 breeds of
Animals—12 clinically normal dogs (6 Greyhounds
and 6 Labrador Retrievers) with no history of hind
Procedure—Small retroreflective markers were
applied to the skin over the pelvic limb joints, and a 4-
camera kinematic system captured data at 200 Hz in
tandem with force platform data while the dogs trotted
on a runway. Breed-specific morphometric data
were combined with kinematic and force data in an
inverse-dynamics solution for stance-phase net joint
moments and powers at the stifle, tarsal, and MTP
Results—There were gross differences in kinematic
patterns between Greyhounds and Labradors. At the
stifle and tarsal joints, moment and power patterns
were similar in shape, but amplitudes were larger for
the Greyhounds. The MTP joint was a net absorber of
energy, and this was greater in the Greyhounds.
Greyhounds had a positive phase across the stifle,
tarsal, and MTP joints at the end of stance for an
active push-off, whereas for the Labrador Retrievers,
the only positive phase was across the tarsus, and
this was small, compared with values for the
Conclusions and Clinical Relevance—Gross differences
in pelvic limb mechanics are evident between
Greyhounds and Labrador Retrievers. Joint kinetics in
specific dogs should be compared against breed-specific
patterns. (Am J Vet Res 2005;66:1563–1571)
Objective—To biomechanically and histologically compare single-layer continuous Cushing and simple continuous appositional cystotomy closure in rats with xylene-induced cystitis.
Animals—40 female Sprague-Dawley rats.
Procedure—Rats were anesthetized, their urinary bladders catheterized and evacuated, and xylene instilled in each bladder for 5 minutes and then aspirated. Forty-eight hours later, ventral midline celiotomy and cystotomy (8 mm) were performed. Cystotomies were closed with 6-0 poliglecaprone 25 by use of a single-layer continuous Cushing or simple continuous appositional pattern (20 rats/group), and cystotomy times were recorded. Rats were allocated to healing durations (5 rats/group) of 0, 3, 7, and 14 days. Celiotomies were closed in a routine manner. After the allotted healing interval, another celiotomy was performed, the urethra cannulated, and ureters ligated. The cannula was secured to the urethra, and the bladder infused at 0.1 mL/min. Leak pressure volume, leak pressure, peak pressure volume, and peak pressure were recorded via a pressure transducer. Bladders were harvested and histologically assessed.
Results—Cystotomy time, biomechanical testing values, and overall inflammation scores did not differ between closure methods for any healing duration. Both methods had significantly greater leak pressures, with the appositional method also having significantly greater peak pressures on day 7, compared to day 0. Biomechanical testing values decreased from day 7 to 14 as a result of juxtaincisional weakening of the bladder and xylene-induced changes in collagen.
Conclusions and Clinical Relevance—Simple continuous appositional was equal biomechanically and histologically to continuous Cushing for all comparison variables. Poliglecaprone 25 was acceptable for cystotomy closure.
Objective—To determine whether renal crystals can be experimentally induced in animals fed melamine or the related triazine compound cyanuric acid, separately or in combination, and to compare experimentally induced crystals with those from a cat with triazine-related renal failure.
Animals—75 fish (21 tilapia, 24 rainbow trout, 15 channel catfish, and 15 Atlantic salmon), 4 pigs, and 1 cat that was euthanatized because of renal failure.
Procedures—Fish and pigs were fed a target dosage of melamine (400 mg/kg), cyanuric acid (400 mg/kg), or melamine and cyanuric acid (400 mg of each compound/kg) daily for 3 days and were euthanatized 1, 3, 6, 10, or 14 days after administration ceased. Fresh, frozen, and formalin-fixed kidneys were examined for crystals. Edible tissues were collected for residue analysis. Crystals were examined for composition via Raman spectroscopy and hydrophilic-interaction liquid chromatography–tandem mass spectrometry.
Results—All animals fed the combination of melamine and cyanuric acid developed goldbrown renal crystals arranged in radial spheres (spherulites), similar to those detected in the cat. Spectral analyses of crystals from the cat, pigs, and fish were consistent with melamine-cyanurate complex crystals. Melamine and cyanuric acid residues were identified in edible tissues of fish.
Conclusions and Clinical Relevance—Although melamine and cyanuric acid appeared to have low toxicity when administered separately, they induced extensive renal crystal formation when administered together. The subsequent renal failure may be similar to acute uric acid nephropathy in humans, in which crystal spherulites obstruct renal tubules.