bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic and electrophysiologic effects of ontazolast in dogs
Authors: Hamlin Robert L. , Nakayama Tomohiro , Brady Joe T. , Stoll Ray E.
Published: December 2005

Objective—To determine whether QT interval is prolonged
or sudden death is caused by ventricular fibrillation
resulting from torsades de pointes and to identify
hemodynamic effects of ontazolast.

Animals—28 Beagles.

Procedure—Physiologic variables were measured for
2 hours in conscious dogs given ontazolast (0, 1, or 3
mg/kg of body weight, IV) and for 1 hour in anesthetized
dogs given cumulative doses of ontazolast
(0, 1, 3, 6, or 8 mg/kg, IV).

Results—Ontazolast prolonged QT interval and QT
interval corrected for heart rate (QTc) at doses of 6
mg/kg in anesthetized dogs. At 8 mg/kg, both variables
remained prolonged but tended to decrease.
In conscious dogs, ontazolast increased QT interval
and QTc 15 minutes after administration, but both
variables returned to reference ranges by 60 minutes.
In conscious dogs, ontazolast increased maximum
rate of increase of left ventricular pressure
and maximal velocity of fiber shortening, indicators
of inotropy, and increased tau, indicating a
decreased rate of relaxation. One conscious dog
receiving 3 mg/kg developed nonfatal torsades de
pointes, but another conscious dog developed ventricular
fibrillation. Two anesthetized dogs receiving
6 mg/kg developed early afterdepolarizations, and
all dogs developed secondary components in their T
waves.

Conclusion and Clinical Relevance—Ontazolast
possesses potent class-III antiarrhythmic properties
and induces prolongation of QTc in a dose-dependent
fashion. Because there was a clear dosedependent
prolongation of QT interval in all
instances, ontazolast may serve as a positive-control
compound for studying other compounds that are
believed to prolong the QT interval. (Am J Vet Res
2000;61:1364–1368)
Effect of sodium bisulfate on skin and hooves of horses
Authors: Sweeney Corinne R. , Habecker Perry L. , Russell Gail E.
Published: December 2005

Objective—To evaluate the safety of sodium bisulfate for use in horse barn environments by determining its irritant effect on skin and hooves.

Animals—6 female mixed-breed ponies.

Procedure—Sodium bisulfate was applied to clipped intact skin of 6 ponies to evaluate its irritant effect after single (48 hours) and repetitive (6 h/d for 10 days) applications; similar areas of skin were used as untreated control sites. In addition, sodium bisulfate was applied to the sole of both front hooves of each pony and covered with wet gauze, and the entire hoof was covered with adhesive tape for 48 hours.

Results—Contact with moistened sodium bisulfate for 48 hours had no effect on pony skin. Contact with sodium bisulfate for 6 hours on 10 consecutive days did not cause gross changes but did cause mild to moderate microscopic changes including epidermal necrosis, hyperkeratosis, capillary congestion, edema, and diffuse mixed inflammatory cell infiltrate. All changes were limited to the epidermis and superficial dermis. Gross changes in hoof sole, signs of lameness, and increase in digital pulse pressure or pulse intensity were not detected.

Conclusions and Clinical Relevance—Duration of contact with sodium bisulfate in this study was in excess of that expected under typical husbandry conditions. Despite this fact, gross changes in skin and hooves were not detected. Microscopic lesions were confined to the epidermis and superficial dermis. Results suggest that contact with sodium bisulfate under these conditions is safe. (Am J Vet Res2000;61:1418–1421)
Evaluation of results for Schirmer tear tests conducted with and without application of a topical anesthetic in clinically normal dogs of 5 breeds
Authors: Hamor Ralph E. , Roberts Steven M. , Severin Glenn A. , Chavkin Matthew J.
Published: December 2005

Objective—To evaluate, for clinically normal dogs, results of Schirmer tear tests in eyes without topical anesthetic (STT) and to detect differences associated with breed, sex, age, day, and time of day in eyes in which STT was performed after use of topical anesthetic (STTa).

Animals—41 Beagles, 43 Labrador Retrievers, 25 Golden Retrievers, 26 English Springer Spaniels, and 22 Shetland Sheepdogs.

Procedure—Beagles had STT and STTa values measured twice daily for 5 days. Client-owned dogs of 4 other breeds had STT and STTa values measured once.

Results—Mean ± SD values of Beagles for STT and STTa were 20.2 ± 2.5 and 3.8 ± 2.7 mm/min. Mean values for STT and STTa were as follows: Labrador Retriever, 22.9 ± 4.1 and 9.6 ± 3.8 mm/min; English Springer Spaniel; 20.7 ± 3.2 and 5.4 ± 3.4 mm/min; Golden Retriever, 21.8 ± 3.7 and 8.8 ± 3.1 mm/min; and Shetland Sheepdog, 15.8 ± 1.8 and 3.6 ± 2.8 mm/min. Overall mean values for STT and STTa were 20.2 ± 3.0 and 6.2 ± 3.1 mm/min. Differences for STT and STTa were detected among breeds, but significant differences were not associated with sex or age within each breed or in overall values for all dogs.

Conclusions and Clinical Relevance—Results for the STT reported here compare favorably with reported values, except for results of Shetland Sheepdogs; however, results for the STTa differ dramatically from reported values. Clinicians should consider effects attributable to breed when evaluating results of STT and STTa in dogs. (Am J Vet Res2000; 61:1422–1425)
Determination of the lactate breakpoint during incremental exercise in horses adapted to dietary corn oil
Authors: Kronfeld David S. , Custalow S. Elizabeth , Ferrante Pamela L. , Taylor Lynn E. , Moll H. David , Meacham Thomas N. , Tiegs Wilfried
Published: December 2005

Objective—To determine lactate breakpoint of horses and test for effects of training and dietary supplementation with corn oil on that breakpoint.

Animals—7 healthy Arabian horses.

Procedures—Horses received a control diet (n = 4) or a diet supplemented with 10% corn oil (4). A training program, which comprised two 5-week conditioning periods with 1 week of rest, was initiated. Submaximal incremental exercise tests (IET) were conducted before the first and after both conditioning periods. Blood samples for determination of blood lactate and plasma glucose concentrations were collected 1 minute before IET and during the 15 seconds immediately preceding each speed change. Data collected were fit to one- and twoslope broken-line models and an exponential model.

Results—Good fits were obtained by application of the broken-line models (adjustedR2> 0.92) to blood lactate concentration versus speed curves. Lactate breakpoints increased 41% after training but were not affected by diet. After training, slope 2 and peak blood lactate concentrations were greater in the corn oil group, compared with controls. Mean blood lactate concentration at the breakpoint was not affected by training or diet. Plasma glucose concentration versus speed curves also fit the broken-line models, and glucose breakpoints preceded lactate breakpoints by approximately 1 m/s in the second and third IET.

Conclusions and Clinical Relevance—Lactate breakpoints can be determined for horses, using blood lactate concentration versus speed curves generated during submaximal IET and may be useful for assessing fitness and monitoring training programs in equine athletes. (Am J Vet Res2000;61:144–151)
Effects of L-lysine and L-arginine on in vitro replication of feline herpesvirus type-1
Authors: Maggs David J. , Collins B. Keith , Thorne James G. , Nasisse Mark P.
Published: December 2005

Objective—To determine the effects of varios concentrations of L-lysine and L-arginine on in vitro replication of feline herpesvirus type-1 (FHV-1).

Sample Population—Cultured Crandell-Reese feline kidney (CRFK) cells and FHV-1 strain 727.

Procedure—Uninfected CRFK cells or CRFK cells infected with FHV-1 were cultured in Dulbecco's modified Eagle's medium or in 1 of 7 test media containing various concentrations of lysine and arginine. Viral titer and CRFK growth rate were assessed in each medium.

Results—Media depleted of arginine almost completely inhibited viral replication, whereas 2.5 or 5.0 µg of arginine/ml of media was associated with a significant increase in FHV-1 replication. In media with 2.5 µg of arginine/ml, supplementation with 200 or 300 µg of lysine/ml reduced viral replication by 34.2 and 53.9%, respectively. This effect was not seen in media containing 5.0 µg of arginine/ml. Growth rates of CRFK cells also were suppressed in media containing these concentrations of amino acids, but they were not significantly different from each other.

Conclusions and Clinical Relevance—Arginine exerts a substantial growth-promoting effect on FHV-1. Supplementation of viral culture medium with lysine attenuates this growth-promoting effect in media containing low concentrations of arginine. Analysis of data from this study indicates that high concentrations of lysine reduce in vitro replication of FHV-1 but only in media containing low concentrations of arginine. Clinical trials will be necessary to determine whether supplemental administration of lysine, with or without arginine restriction, will be useful in the management of cats with FHV-1 infections. (Am J Vet Res2000; 61:1474–1478)
In vitro effects of 5-hydroxytryptamine and cisapride on the circular smooth muscle of the jejunum of horses
Authors: Nieto Jorge E. , Snyder Jack R. , Kollias-Baker Cynthia , Stanley Scott
Published: December 2005

Objective—To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses.

Sample Population—Jejunal muscle strips from 8 horses.

Procedure—Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined.

Results—Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (Emax) of 1,151 ± 214 g/cm2and a molar concentration that induces contractile force equal to 50% of maximum response (EC50) of 0.028 ± 0.002 µM. Prior incubation with the 5-HT2antagonist ketanserin decreased the Emax(626 ± 147 g/cm2) and potency (EC50, 0.307 ± 0.105 µM) of 5-HT. Prior incubation with the 5-HT3antagonist tropisetron decreased the efficacy (Emax, 894 ± 184 g/cm2) to 5-HT. Cisapride also caused a concentrationdependent increase in contractile amplitude, with an Emaxof 331 ± 82 g/cm2and an EC50of 0.302 ± 0.122 µM. Prior incubation with ketanserin decreased the Emax(55 ± 17 g/cm2) and potency (EC50, 0.520 ± 0.274 µM) of cisapride.

Conclusion and Clinical Relevance—Stimulatory effects of 5-HT and cisapride on circular smooth muscle of equine jejunum are mediated primarily through a noncholinergic effect. The effects of 5-HT are mediated, at least partially, by 5-HT2and 5-HT3receptors, whereas the effects of cisapride are mediated primarily by 5-HT2receptors. This may impact treatment of horses with postoperative ileus. (Am J Vet Res2000;61:1561–1565)
Effects of intravenous infusion of guaifenesin on electroencephalographic variables in pigs
Authors: Haga Henning A. , Moerch Henning , Soli Nils E.
Published: December 2005

Objective—To investigate the sedative effects of
guaifenesin in pigs by use of electroencephalography.

Animals—10 Norwegian Landrace pigs (5 castrated
males and 5 sexually intact females).

Procedure—Guaifenesin (150 mg/kg of body weight,
IV) was administered during a 5-minute period. Using
a 2-channel referential electrode configuration, electroencephalograms
were recorded before, during,
and after infusion of guaifenesin. Changes in spectral
edge frequency 95% (SEF), median frequency (MED),
and total power were evaluated.

Results—After administration of guaifenesin, SEF
decreased significantly, and total power increased significantly;
however, MED did not change significantly.
Analysis of the data did not reveal differences
between pigs on the basis of sex.

Conclusions and Clinical Relevance—We concluded
that guaifenesin synchronized the patterns of electroencephalograms.
This is a strong indication that the
drug has a sedative effect in pigs. (Am J Vet Res
2000;61:1599–1601)
Gastrointestinal volatile fatty acid concentrations and pH in cats
Authors: Brosey Bess P. , Hill Richard C. , Scott Karen C.
Published: December 2005

Objective—To measure volatile fatty acid (VFA) concentrations and pH in the gastrointestinal tracts of healthy adult cats fed a commercial dry cat food.

Animals—14 cats.

Procedure—The gastrointestinal tracts were excised immediately after euthanasia and divided into 6 sections (stomach, duodenum, jejunum, ileum, proximal portion of the colon, and distal portion of the colon). Luminal contents were collected from each segment, pH was measured, and contents were centrifuged. The supernatant was analyzed for acetate, proprionate, butyrate, isobutyrate, valerate, and isovalerate concentrations by use of gas chromatography.

Results—Mean total VFA concentrations were lowest in the stomach (20 mmol/L); increased through the duodenum, jejunum, and ileum (30, 29, and 41 mmol/L, respectively); and were greatest in the proximal and distal portions of the colon (109 and 131 mmol/L, respectively). Estimated mean total VFA amounts were low (< 600 μmol) throughout all segments of the gastrointestinal tract; pH values increased from the stomach through the ileum and subsequently decreased in the colon.

Conclusions and Clinical Relevance—Total VFA concentrations in the colon were comparable to values reported for the forestomach of ruminants and large intestines of monogastric animals, whereas values in the small intestine were higher than reported for other species. Total VFA amounts were low, consistent with the short, nonvoluminous gastrointestinal tract of carnivores. Luminal pH varied throughout the gastrointestinal tract in a pattern similar to other monogastric animals. Volatile fatty acids probably contribute minimal metabolic energy in cats but may be important in the maintenance of local mucosal health. (Am J Vet Res2000;61:359–361)
Acute, subchronic, and chronic toxicity of ecadotril in dogs
Authors: Maertins Thomas , Keutz Eckhard von , Goetze Leopold
Published: December 2005

Objective—To determine the toxicity of ecadotril in
dogs.

Animals—74 healthy 4- to 11-month-old Beagles.

Procedure—To determine acute toxicity, ecadotril
(2,000 mg/kg of body weight, PO) in a gelatin capsule
was administered once to 2 dogs, and dogs were
observed for 2 weeks. To determine subchronic and
chronic toxicity, ecadotril was administered every day
for 3 months (50 mg/kg [n = 8], 100 mg/kg [8],
300 mg/kg [12]) and 12 months (25 mg/kg [n = 8],
50 mg/kg [8], 100 mg/kg [8]), respectively. Dogs in
control groups (n = 12 or 8) received an empty gelatin
capsule. Physical examinations, CBC, plasma biochemical
analyses, and urinalyses were performed
before and at various times during each experiment.
Dogs were euthanatized at the end of each experiment,
and necropsies were performed.

Results—Dogs that received 1 dose of 2,000 mg of
ecadotril/kg developed nonspecific clinical signs of toxicosis.
Dogs that received 300 mg of ecadotril/kg/d for 3
months developed pronounced anemia, bone marrow
suppression, and some evidence of liver impairment.
There was no evidence of an effect accumulated over
time, and reversibility of toxic effects was evident.
Dogs that received ≤ 100 mg of ecadotril/kg/d for 3 or
12 months tolerated treatment without apparent effect.

Conclusions and Clinical Relevance—Degree of
acute toxicity of a single high dose of ecadotril in dogs
was low. The no-observable adverse effect level of
ecadotril following daily oral administration was
100 mg/kg/d; repeated administration of 300 mg/kg/d
revealed the hematopoietic system as the primary
toxicologic target. (Am J Vet Res 2000;61:425–429)
Effects of dietary potassium citrate supplementation on urine pH and urinary relative supersaturation of calcium oxalate and struvite in healthy dogs
Authors: Stevenson Abigail E. , Wrigglesworth David J. , Smith Brigitte H. E. , Markwell Peter J.
Published: December 2005

Objective—To assess the effect of dietary potassium citrate supplementation on the urinary pH, relative supersaturation of calcium oxalate and struvite (defined as the activity product/solubility product of the substance), and concentrations of magnesium, ammonium, phosphate, citrate, calcium, and oxalate in dogs.

Animals—12 healthy adult dogs.

Procedure—Canned dog food was fed to dogs for 37 days. Dogs were randomly allocated to 3 groups and fed test diets for a period of 8 days. Study periods were separated by 6-day intervals. During each study period the dogs were fed either standard diet solus (control) or standard diet plus 1 of 2 types of potassium citrate supplements (150 mg potassium citrate/kg of body weight/d) twice daily. Urinary pH, volume and specific gravity, relative supersaturation of calcium oxalate and struvite, and concentrations of magnesium, ammonium, phosphate, calcium, oxalate, and citrate were assessed for each treatment.

Results—Mean urine pH was not significantly affected by dietary potassium citrate supplementation, although urine pH did increase by 0.2 pH units with supplementation. Diets containing potassium citrate maintained a higher urine pH for a longer part of the day than control diet. Three Miniature Schnauzers had a significantly lower urinary relative calcium oxalate supersaturation when fed a diet supplemented with potassium citrate, compared with control diet.

Conclusions and Clinical Relevance—Dietary potassium citrate supplementation has limited effects on urinary variables in most healthy dogs, although supplementation results in maintenance of a higher urine pH later in the day. Consequently, if supplementation is introduced, dogs should be fed twice daily and potassium citrate should be given with both meals or with the evening meal only. (Am J Vet Res2000;61:430–435)
Inheritance of gluten-sensitive enteropathy in Irish Setters
Authors: Garden Oliver A. , Pidduck Heather , Lakhani Ken H. , Walker Dawn , Wood James L. N. , Batt Roger M.
Published: December 2005

Objective—To establish a model for inheritance of gluten-sensitive enteropathy (GSE) in Irish Setters.

Animals—44 dogs of a 6-generation family of Irish Setters with GSE and 7 healthy Irish Setters.

Procedure—Phenotype of each dog was determined after oral administration of gluten in the weaning diet, using morphometric evaluation of jejunal biopsies (all generations) and measurement of small intestinal permeability by use of a lactulose-rhamnose permeation test (generations 1, 2, and 3). Overall probability for each of 4 genetic models of inheritance (autosomal recessive, autosomal dominant, sex-linked recessive, and sex-linked dominant) accounting for segregation of partial villus atrophy within the entire family was calculated.

Results—The autosomal recessive model was most tenable and was 56,250 times more likely to account for segregation of partial villus atrophy than the autosomal dominant model, assuming disease prevalence of 0.8%. Both sex-linked models were untenable. These conclusions were robust to the error attached to estimation of disease prevalence. High intestinal permeability without morphometric jejunal abnormalities in 4 of 20 dogs in the 3 youngest generations suggested heterogeneity of lesions associated with GSE.

Conclusions—Genetic transmission of GSE is under the control of a single major autosomal recessive locus. (Am J Vet Res2000;61:462–468)
Nitric oxide metabolite production in the cranial cruciate ligament, synovial membrane, and articular cartilage of dogs with cranial cruciate ligament rupture
Authors: Spreng David , Sigrist Nadja , Jungi Thomas , Busato André , Lang Johann , Pfister Hedi , Schawalder Peter
Published: December 2005

Objective—To measure concentrations of nitric oxide metabolites (nitrite-nitrate [NOt]) in cartilage, synovial membrane, and cranial cruciate ligament (CCL) in dogs and evaluate associations with osteoarthritis in dogs with CCL rupture.

Animals—46 dogs with CCL rupture and 54 control dogs without joint disease.

Procedure—Tissue specimens for histologic examination and explant culture were harvested during surgery in the CCL group or immediately after euthanasia in the control group; NOt concentrations were measured in supernatant of explant cultures and compared among dogs with various degrees of osteoarthritis and between dogs with and without CCL rupture.

Results—Osteoarthritic cartilage had significantly higher NOt concentration (1,171.6 nmol/g) than did healthy cartilage (491.0 nmol/g); NOt concentration was associated with severity of macroscopic and microscopic lesions. Synovial membrane NOt concentration did not differ between dogs with and without CCL rupture. Ruptured CCL produced less NOt than did intact ligaments. In control dogs, NOt concentrations were similar for intact ligaments (568.1 nmol/g) and articular cartilage (491.0 nmol/g). Synthesis of NOt was inhibited substantially by coincubation with inhibitors.

Conclusions and Clinical Relevance—Results suggest that NOt in canine joint tissues originates from the inducible nitric oxide synthase pathway. Nitric oxide metabolite production in cartilage was greater in dogs with osteoarthritis than in healthy dogs and was associated with lesion severity, suggesting that nitric oxide inhibitors may be considered as a treatment for osteoarthritis. The CCL produces substantial concentrations of NOt; the importance of this finding is unknown. (Am J Vet Res2000;61:530–536)
Effects of phenylbutazone on bone activity and formation in horses
Authors: Rohde Carsten , Anderson David E. , Bertone Alicia L. , Weisbrode Stephen E.
Published: December 2005

Objective—To determine the effects of phenylbutazone (PBZ) on bone activity and bone formation in horses.

Animals—12 healthy 1- to 2-year-old horses.

Procedures—Biopsy was performed to obtain unicortical bone specimens from 1 tibia on day 0 and from the contralateral tibia on day 14. Fluorochromic markers were administered IV 2 days prior to and on days 0, 10, 15, and 25 after biopsy was performed. Six horses received PBZ (4.4 mg/kg of body weight, PO, q 12 h) and 6 horses were used as controls. All horses were euthanatized on day 30 and tissues from biopsy sites, with adjacent cortical bone, were collected. Osteonal density and activity, mineral apposition rate (MAR), and percentage of mineralized tissue filling the biopsy-induced defects in cortical bone were assessed. Serum samples from all horses were analyzed for bone-specific alkaline phosphatase activity and concentration of PBZ.

Results—MAR was significantly decreased in horses treated with PBZ. Regional acceleratory phenomenon was observed in cortical bone in both groups but was significantly decreased in horses treated with PBZ. Osteonal activity was similar at all time points in all horses. In control horses, percentage of mineralized tissue filling the cortical defects was significantly greater in defects present for 30 days, compared with defects present for 14 days. Differences in percentage of mineralized tissue were not detected in horses treated with PBZ.

Conclusions and Clinical Relevance—PBZ decreased MAR in cortical bone and appeared to decrease healing rate of cortical defects in horses. (Am J Vet Res2000;61:537–543)
Microcrack density and length in the proximal and distal metaphyses of the humerus and radius in dogs
Authors: Muir Peter , Ruaux-Mason Caroline P.
Published: December 2005

Objective—To compare microcrack density and length in the proximal and distal metaphyses of the humerus and radius in dogs.

Sample Population—Left humerus and radius from each of 10 dogs of medium to large size.

Procedure—Metaphyseal specimens were bulk stained in 1% basic fuchsin in graded alcohols and embedded in methylmethacrylate. For quantification of fatigue-induced microscopic damage, transverse sections were prepared from proximal and distal metaphyseal regions, and length and density of microcracks were determined, using light microscopy.

Results—Bone region, age, and body weight were not significantly associated with microcrack density or length.

Conclusions and Clinical Relevance—The hypothesis that fatigue-induced injury (increased microcrack density and length) caused by cyclic loading associated with daily activity is greater in bone regions prone to development of osteosarcoma was not supported by data from this study. (Am J Vet Res2000;61:6–8)
Development and validation of an enzyme-linked immunosorbent assay for feline trypsin-like immunoreactivity
Authors: vet Jörg M. Steiner, vetmed,Dr med , Williams David A. , Moeller Erik M. , Melgarejo Tonatiuh
Published: December 2005

Objective—To develop and validate an ELISA for quantitative analysis of feline trypsin-like immunoreactivity (fTLI).

Sample Population—Purified feline cationic trypsin (fCT) and rabbit anti-fCT antiserum; blood samples from 63 healthy cats.

Procedures—A sandwich capture ELISA was developed, using anti-fCT antiserum purified by affinity chromatography that underwent biotinylation. Purified fCT was used for standards. The assay was validated by determination of sensitivity, working range, linearity, accuracy, precision, and reproducibility. A reference range was established by assaying serum samples from the 63 healthy cats.

Results—Sensitivity was 1.23 µg/L; working range was 2 to 567 µg/L. Ratios of observed versus expected results for 4 samples tested at various dilutions ranged from 90.0 to 120.7%. Ratios of observed versus expected results for 5 samples spiked with various concentrations of fCT ranged from 82.0 to 101.8%. Intra- and inter-assay coefficients of variability ranged from 9.9 to 11.1% and from 10.2 to 21.7%, respectively. The reference range for serum fTLI measured with this ELISA was 12 to 82 µg/L.

Conclusions and Clinical Relevance—Results suggest that an ELISA can be used to measure serum fTLI in cats. The ELISA was sufficiently sensitive, linear, accurate, precise, and reproducible for clinical use. (Am J Vet Res2000;61:620–623)
Pharmacokinetics of pentoxifylline in dogs after oral and intravenous administration
Authors: Marsella Rosanna , Nicklin Constance F. , Munson John W. , Roberts Stephen M.
Published: December 2005

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.

Animals—7 sexually intact, female, mixed-breed dogs.

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)
Esophageal transit of capsules in clinically normal cats
Authors: Graham John P. , Lipman Alan H. , Newell Susan M. , Roberts Gregory D.
Published: December 2005

Objective—To evaluate the esophageal passage of capsules in clinically normal cats and determine the incidence of prolonged transit or entrapment.

Animals—12 clinically normal adult cats.

Procedure—Esophageal transit of barium sulfatefilled capsules was evaluated fluoroscopically. Each cat was examined 3 times (36 examinations). Esophageal transit times were classified as normal (≤ 30 seconds) or prolonged (> 30 but ≤ 240 seconds). Capsules were considered entrapped when transit times were > 240 seconds.

Results—Transit times were normal in 10 of the 36 (27.8%) examinations, whereas times were prolonged in 7 (19.4%) examinations. Capsules became entrapped in the midcervical region of the esophagus during 19 (52.8%) examinations. Following termination of each examination, cats with entrapped capsules were fed a small amount (0.5 to 1 ounce) of food; this resulted in passage of the capsule to the stomach.

Conclusions and Clinical Relevance—The possibility of medication-induced esophagitis should be considered when orally administering ulcerogenic drugs to cats. It is recommended that a small volume of food be given following medications to ensure complete esophageal clearance. (Am J Vet Res2000;61: 655–657)
Effect of sodium butyric acid, sodium valerianic acid, and osmolarity on contractility of specimens of intestinal wall obtained from the cecum and spiral colon of healthy cows
Authors: Allemann Monika , Eicher Richard , Mevissen Meike , Haltiner René , Meylan Mireille , Steiner Adrian
Published: December 2005

Objective—To compare the effect of various concentrations of sodium butyric acid and sodium valerianic acid, as well as various osmolarities, on contractility of ex-vivo intestinal wall specimens obtained from the cecum and spiral colon of each of several healthy cows.

Sample Population—Full-thickness preparations of intestinal wall, dissected parallel to the longitudinal smooth muscle layers, harvested from freshly slaughtered healthy cows.

Procedure—Specimens of intestinal wall were incubated for 5 minutes with various concentrations of sodium butyric acid and sodium valerianic acid as well as various osmolar concentrations of NaCl, using a crossover design. Isometric contractions were induced 7 times with carbachol (CH; 5 X 10–6mol/L). Contractility was defined as the maximum amplitude of contraction and the amplitude of contraction 2 minutes after addition of CH.

Results—Repeated addition of CH did not result in a significant effect on contractility of specimens from the cecum and spiral colon. Contractility after addition of CH was not significantly affected by prior incubation with various concentrations of sodium butyric acid or sodium valerianic acid or after an increase of osmolarity. Maximum amplitude of contraction was significantly higher in specimens from the spiral colon, compared with specimens from the cecum.

Conclusions—Increases in concentrations of sodium butyric acid or sodium valerianic acid and increases in osmolarity did not inhibit contractility of intestinal wall specimens from the cecum and spiral colon of a group of healthy cows. (Am J Vet Res2000;61: 678–683)
Effects of human recombinant interleukin-1β on canine articular chondrocytes in three-dimensional culture
Authors: Cook James L. , Anderson C. Collins , Kreeger John M. , Tomlinson James L.
Published: December 2005

Objective—To determine the effects of interleukin (IL)-1β on matrix synthesis and degradation by chondrocytes cultured in a 3-dimensional (3-D) gel medium.

Sample Population—Chondrocytes from 7 dogs.

Procedure—Articular chondrocytes were harvested and cultured in 3-D gel medium alone or with 10 or 20 ng IL-1βml that was added beginning on day 0, 3, 6, or 9. On days 3, 6, 12, and 20 of 3-D culture, samples of the liquid medium were evaluated for glycosaminoglycan (GAG), prostaglandin E2(PGE2), and matrix metalloprotease (MMP)-3 content. The 3-D plug in each well was evaluated for histologic characteristics of viability, cell morphology, and proteoglycan staining, immunohistochemically stained for collagen type II, and spectrophotometrically analyzed for GAG content.

Results—Significant differences for all variables were detected between controls and each IL-1β group, among groups with different IL-1β concentrations, and among groups with IL-1β added at various time points. Chondrocytes exposed to IL-1β had loss of GAG, increased PGE2and MMP-3 concentrations, and lack of collagen type-II synthesis. These IL-1β effects appeared to be time and concentration dependent.

Conclusions—Addition of IL-1β to chondrocytes in 3- D gel medium results in time- and concentrationdependent effects on matrix synthesis and degradation and provides an appropriate in vitro model for many of the pathophysiologic events associated with osteoarthritis. (Am J Vet Res2000;61:766–770)
Hematologic, plasma protein, and biochemical profiles of brown pelicans (Pelecanus occidentalis)
Authors: Zaias Julia , Fox Wendy P. , Cray Carolyn , Altman Norman H.
Published: December 2005

Objective—To establish hematologic and biochemical
reference values for the brown pelican (Pelecanus
occidentalis).

Animals—31 captive, healthy, but permanently disabled
pelicans and 35 wild-caught, healthy pelicans
from a rehabilitation facility on the east coast of
Florida.

Procedures—Samples of venous blood were collected
from each pelican, and hematologic, plasma biochemical,
and electrophoretic protein analyses were
performed. Student t-tests were used to compare
blood values between captive versus wild-caught,
adult male versus adult female, and adult versus juvenile
pelicans.

Results—Hematologic and electrophoretic values
were similar between male and female, adult and
juvenile, and captive and wild-caught pelicans.
Significant sex differences existed for plasma calcium
and triglyceride concentrations. Plasma concentrations
of calcium, cholesterol, and CO2 content differed
between captive and wild-caught adults. No significant
differences were found between wild-caught
adult and juvenile pelicans.

Conclusions and Clinical Relevance—Our plasma
biochemical results are similar to those of other brown
pelicans and confamilial species. Additional studies on
seabirds are encouraged, as age, sex, reproductive
status, feeding habits, and captivity are important variables
for health assessment in this and other aquatic
species. (Am J Vet Res 2000;61:771–774)
Pharmacokinetics of the insulin-sensitizing agent troglitazone in cats
Authors: Michels Gina M. , Boudinot F. Douglas , Ferguson Duncan C. , Hoenig Margarethe
Published: December 2005

Objective—To determine pharmacokinetics of troglitazone in healthy cats after IV and oral administration of a single dose of the drug.

Animals—5 healthy ovariohysterectomized adult cats.

Procedure—Using a randomized crossover design, cats were given 5 mg of troglitazone/kg of body weight IV and 40 mg of troglitazone/kg orally. Blood and urine samples were collected after drug administration, and concentrations of troglitazone in plasma and urine were determined by use of high-performance liquid chromatography.

Results—Area-moment analysis was used to calculate pharmacokinetic variables. Terminal phase half-life was 1.1 ± 0.1 hours. Steady-state volume of distribution was 0.23 ± 0.15 L/kg. After IV administration, clearance was 0.33 ± 0.04 L/h/kg. Drug was not detected in urine samples. Mean bioavailability of orally administered troglitazone was 6.9%.

Conclusions and Clinical Relevance—The overall disposition of troglitazone in cats was similar to that reported in other species, including humans. Troglitazone has low and variable oral bioavailability. Clearance of the compound is moderate. Little if any unchanged troglitazone is excreted in urine; thus, metabolism and biliary excretion play predominant roles in elimination of the drug. On the basis of troglitazone pharmacokinetics in healthy cats, as well as on the basis of pharmacodynamics of the drug in humans and other animals, a regimen that uses a dosage of 20 to 40 mg/kg administered orally once or twice per day to cats will produce plasma concentrations of the insulin-sensitizing agent that have been documented to be effective in humans. (Am J Vet Res2000;61:775–778)
Relationship between serum leptin immunoreactivity and body fat mass as estimated by use of a novel gas-phase Fourier transform infrared spectroscopy deuterium dilution method in cats
Authors: Backus Robert C. , Havel Peter J. , Gingerich Ronald L. , Rogers Quinton R.
Published: December 2005

Objective—To validate a recently developed commercially available leptin radioimmunoassay (RIA) for use with feline serum and evaluate the relationship between serum leptin concentrations and body fat mass in domestic cats.

Animals—19 sexually intact male specific–pathogenfree domestic cats that weighed 3.8 to 7.1 kg and were 1.1 to 3.5 years old.

Procedure—Specificity for feline leptin was evaluated by use of gel filtration chromatography and reversephase high-performance liquid chromatography fractionation of serum. Body fat mass was determined by use of the deuterium oxide (D2O) dilution method. Serum water D2O enrichment was measured by use of gas-phase Fourier transform infrared spectroscopy.

Results—Body fat mass and percentage body fat ranged from 0.3 to 2.3 kg and 7.5 to 34.9%, respectively. Serum leptin concentrations were lower in the unfed versus the fed state and ranged between 1.6 and 4.9 ng/ml human equivalent (HE); mean ± SD value was 2.9 ± 0.2 ng/ml HE. Leptin concentrations increased with increasing body fat mass and percentage of body fat.

Conclusions—Leptin is in the serum of domestic cats in free (> 78%) and apparently bound forms. The relationship between body fat and serum leptin concentration was similar to that observed in humans and rodents and indicative of a lipostatic role for leptin in cats. Cats that have an overabundance of body fat appear to be less sensitive to the weight-normalizing action of leptin than cats of ideal body condition. (Am J Vet Res2000;61:796–801)
Pharmacokinetics of clomipramine in dogs following single-dose and repeated-dose oral administration
Authors: King Jonathan N. , Maurer Max P. , Altmann Bernd O. , Strehlau Günther A.
Published: December 2005

Objective—To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs following singledose and repeated-dose oral administration at various dosages.

Animals—9 male and 9 female Beagles.

Procedures—Clomipramine was administered orally at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female dogs, first as a single dose and then, after an interval of 14 days, twice daily for 10 days. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method.

Results—Dose-related accumulation was detected following repeated-dose administration. Accumulation ratios after administration of clomipramine at dosages of 1, 2, and 4 mg/kg twice daily were 1.4, 1.6, and 3.8, respectively, for clomipramine and 2.1, 3.7, and 7.6, respectively, for desmethylclomipramine. Terminal half-life increased slightly (1.6-fold for clomipramine and 1.2-fold for desmethylclomipramine) with repeated- dose administration but remained short in all groups (≤ 4 hours). Steady state was reached within 4 days in all animals. Ratios of the areas under the concentration versus time curves from time 0 to 12 hours for clomipramine and desmethylclomipramine were 3.9, 3.1, and 1.5 after repeated administration at dosages of 1, 2, and 4 mg/kg every 12 hours, respectively. Areas under the concentration versus time curve, mean residence times, and terminal half-lives were not significantly different between male and female dogs.

Conclusions and Clinical Relevance—Repeated administration of clomipramine results in higher concentrations of clomipramine than desmethylclomipramine in dogs. (Am J Vet Res2000;61:80–85)
Development and use of a polymerase chain reaction-based diagnostic test for the causal mutation of progressive retinal atrophy in Cardigan Welsh Corgis
Authors: Petersen-Jones Simon M. , Zhu Feng X.
Published: December 2005

Objective—To develop an allele-specific polymerase
chain reaction (ASPCR)-based diagnostic test for the
mutation in the cyclic guanosine monophosphate
phosphodiesterase alpha subunit gene (PDE6A) that
causes the rcd3 form of progressive retinal atrophy
(PRA) in Cardigan Welsh Corgis.

Animals—1 affected homozygote, 1 unaffected carrier,
1 genotypically normal dog, and 500 unknown-
PRA status Cardigan Welsh Corgis.

Procedure—Control blood samples were collected
from Cardigan Welsh Corgis of known PRA status
(ie, affected homozygote, unaffected carrier, and a
genotypically normal dog) for test development. Test
blood samples were collected from 500 Cardigan
Welsh Corgis of unknown PRA status. Genomic
DNA was used as a template in ASPCR. One pair of
primers was designed to specifically amplify only
the mutant allele, and another set to amplify only
the wildtype allele. The PCR conditions were adjusted
to ensure each reaction was 100% specific.

Results—The PCR conditions were identified so that
each ASPCR only amplified the allele it was designed
to amplify. Of the 500 Cardigan Welsh Corgis tested
using the newly developed ASPCR, 457 were
homozygous for the normal allele (genotypically normal),
43 were heterozygous (phenotypically normal
carriers), and none were homozygous for the mutant
allele.

Conclusion and Clinical Relevance—A rapid, ASPCR
diagnostic test able to detect the PDE6A gene mutation
responsible for the rcd3 form of PRA in Cardigan
Welsh Corgis was developed. The test provides a useful
service for Cardigan Welsh Corgi breeders and will
enable them to prevent the birth of homozygote
mutant dogs. (Am J Vet Res 2000;61:844–846.
Altered expression of G proteins in thyroid gland adenomas obtained from hyperthyroid cats
Authors: Hammer Kimberly B. , Holt David E. , Ward Cynthia R.
Published: December 2005

Objective—To determine whether expression of G
proteins (Gi and Gs) is altered in thyroid gland adenomas
obtained from hyperthyroid cats.

Sample Population—Adenomatous thyroid glands
obtained from 8 hyperthyroid cats and thyroid glands
obtained from 4 age-matched euthyroid cats.

Procedure—Expression of Gi and Gs was quantified
in enriched membrane preparations of thyroid gland
tissue, using immunoblotting with Gi and Gs antibodies
and toxin-catalyzed ADP-ribosylation.

Results—Expression of Gi was significantly reduced
in thyroid gland adenomas from hyperthyroid cats,
compared with normal thyroid gland tissue from
euthyroid cats. Expression of Gs was similar between
the 2 groups.

Conclusions and Clinical Relevance—A decrease in
expression of Gi in adenomatous thyroid glands of
cats may reduce the negative inhibition of the cAMP
cascade in thyroid cells, leading to autonomous
growth and hypersecretion of thyroxine.
Understanding the molecular mechanisms for hyperthyroidism
in cats may lead to better treatment or,
ultimately, prevention of the disease. (Am J Vet Res
2000;61:874–879)
Use of pamidronate disodium to reduce cholecalciferol-induced toxicosis in dogs
Authors: Rumbeiha Wilson K. , Fitzgerald Scott D. , Kruger John M. , Braselton W. E. , Nachreiner Raymond , Kaneene John B. , Frese Kris K.
Published: December 2005

Objective—To determine whether pamidronate disodium can reduce cholecalciferol-induced toxicosis in a dose-related manner.

Animals—20 clinically normal, 8- to 12-month-old male Beagles.

Procedure—All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were randomly assigned to 4 groups of 5 dogs each. Dogs were treated with IV administration of 0.9% NaCl solution (SC group), 0.65 mg of pamidronate/kg in 0.9% NaCl solution (LP group), 1.3 mg of pamidronate/kg in 0.9% NaCl solution (MP group), or 2.0 mg of pamidronate/kg in 0.9% NaCl solution (HP group) on days 1 and 4 after administration of CCF. Dogs were observed for 14 days, and serial blood samples were collected for serum biochemical, electrolyte, and 25-hydroxyvitamin D3analyses. Urine samples were collected for determination of specific gravity. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Histologic examination of renal tissue was performed.

Results—One dog in the SC group was euthanatized 3 days after administration of CCF because of severe clinical signs of toxicosis. Dogs in the HP group had significantly higher mean GFR (day 3), serum potassium concentrations (day 14), and urine specific gravity (days 7 and 14) and significantly lower mean serum creatinine concentrations and total calcium × phosphorus concentration product (days 4 and 7) than dogs in the SC group. Dogs in the HP group had no abnormal findings on histologic examination of renal tissue, dogs in the LP and MP groups had trace to mild mineralization of renal tissue, and dogs in the SC group had moderate mineralization and cellular necrosis of proximal renal tubules.

Conclusions and Clinical Relevance—Pamidronate disodium is a potentially useful drug to reduce CCFinduced toxicosis and other causes of hypercalcemia associated with increased bone resorption in dogs. (Am J Vet Res2000;61:9–13)
Molecular epidemioloic analysis of Mycobacterium bovis isolates from Mexico
Authors: Milian-Suazo Feliciano , Salman M. D. , Black IV William C. , Triantis Joni M. , Ramirez Carolina , Payeur Janet B. , Torres Melaine C.
Published: December 2005

Objective—To assess phylogenetic relationships
among Mycobacterium bovis isolates by use of random
amplified polymorphic DNA polymerase chain
reaction (RAPD-PCR) fingerprinting and to relate genetic
profiles of isolates to epidemiologic characteristics.

Animals—400 cattle with tuberculosis.

Procedure—Mycobacterium bovis was isolated from
various organs of cattle slaughtered in 6 geographic
regions of Mexico. Most cattle were adult Holsteins
from large herds that did not participate in a tuberculosis
control program. Four random primers and 2
selected primers were used in RAPD-PCR fingerprinting
of 88 isolates. Pairwise genetic distance between
isolates was obtained and subjected to cluster analysis
with bootstrapping to test for levels of support.

Results—98 different fragments were obtained; there
was broad genetic diversity among isolates, and each
isolate had a unique RAPD-genotype, including those
originating from the same herd. Clustering by geographic
location, affected organ, or severity of lesion
was not detected. Linkage disequilibrium analysis suggested
that M bovis was highly clonal and that mutations
develop at a rapid rate among isolates.

Conclusions and Clinical Relevance—Use of RAPDPCR
could not differentiate M bovis isolates by epidemiologic
characteristics or identify common
sources of infection. (Am J Vet Res 2000;61:90–95)
Serum feline trypsin-like immunoreactivity following administration of ceruletide to healthy cats
Authors: Spillmann Thomas , Jacob Ines , Steiner Jörg M. , Williams David A. , Failing Klaus
Published: December 2005

Objective—To determine changes in serum feline trypsin-like immunoreactivity (fTLI) in response to administration of ceruletide to healthy cats.

Animals—11 healthy cats.

Procedures—Serum fTLI was determined, using a radioimmunoassay, before and 10, 20, 30, 40, and 50 minutes after IM administration of ceruletide (0.3 mg/kg [0.14 mg/lb]).

Results—Mean ± SD baseline serum fTLI was 23.1 ± 4.1 mg/L. There was a statistically significant, but clinically unimportant, increase in serum fTLI 10 and 30 minutes after ceruletide administration.

Conclusions and Clinical Relevance—In healthy cats, administration of ceruletide induced a statistically significant, but clinically unimportant, increase in serum fTLI. Whether responses in cats with exocrine pancreatic disorders would be different is unknown, but results suggest that a ceruletide stimulation test would likely not be useful for differentiating between healthy cats and cats with subclinical chronic exocrine pancreatic disorders. (Am J Vet Res2000;61:925–927)