bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of the antihyperglycemic agent metformin in cats
Authors: Michels Gina M. , Boudinot F. Douglas , Ferguson Duncan C. , Hoenig Margarethe 
Published: January 2024

Abstract

Objective
To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug.

Animals
6 healthy adult ovariohysterectomized cats.

Procedure
In a randomized cross-over design study, each cat was given 25 mg of metformin/kg of body weight, IV and orally. Blood and urine samples were collected after drug administration, and concentrations of metformin in plasma and urine were determined by use of high-performance liquid chromatography.

Results
Disposition of the drug was characterized by a three-compartment model with a terminal phase half-life of (mean ± SD) 11.5 ± 4.2 hours. Metformin was distributed to a small central compartment of 0.057 ± 0.017 L/kg and to 2 peripheral compartments with volumes of distribution of 0.12 ± 0.02 and 0.37 ± 0.38 L/kg. Steady-state volume of distribution was 0.55 ± 0.38 L/kg. After IV administration, 84 ± 14% of the dose was excreted unchanged in urine, with renal clearance of 0.13 ± 0.03 L/h/kg; nonrenal clearance was negligible (0.02 ± 0.02 L/kg). Mean bioavailability of orally administered metformin was 48%.

Conclusions
The general disposition pattern of metformin in cats is similar to that reported for humans. Metformin was eliminated principally by renal clearance; therefore, this drug should not be used in cats with substantial renal dysfunction.

Clinical Relevance
On the basis of our results, computer simulations indicate that 2 mg of metformin/kg administered orally every 12 hours to cats will yield plasma concentrations documented to be effective in humans. (Am J Vet Res 1999;60:738–742)
Urinary orotic acid-to-creatinine ratios in cats with hepatic lipidosis
Authors: VanSteenhouse Jan L. , Dimski Donna S. , Swenson David H. , Taboada Joseph 
Published: January 2024

Abstract

Objective
To determine urinary orotic acid (OA) conentration and evaluate the urinary OA-to-creatinine ratio (OACR) in cats with hepatic lipidosis (HL).

Animals
20 cats with HL and 20 clinically normal cats.

Procedure
Hepatic lipidosis was diagnosed on the basis of clinical signs, results of serum biochemical analyses, exclusion of other concurrent illness, and cytologic or histologic evaluation of liver biopsy specimens. Urine samples were collected from each cat and frozen at −20 C until assayed. Urine creatinine concentrations were determined, using an alkaline picrate method followed by spectrophotometric assay. Urine OA concentration was determined, using high-performance liquid chromatography. Minimum amount of detectable OA in feline urine was 1 µg/ml. Because of small interfering peaks near the base of the OA peak, the minimum quantifiable concentration of OA was determined to be 5 pg/ml. Urinary OACR was compared in both groups of cats.

Results
Differences in urinary OACR were not detected between clinically normal cats and cats with HL. Peaks were not detected for urinary OA in any of the 20 clinically normal cats. Of the 20 HL cats, 14 did not have detectable peaks for urinary OA. Of the 6 HL cats that had detectable urinary OA peaks, 3 had values of < 5 µg/ml.

Conclusions
Apparently, OACR does not increase significantly in cats with HL.

Clinical Relevance
Urinary OACR is not a useful diagnostic test for HL in cats. (Am J Vet Res 1999; 60:753–754)
Effect of protein intake during training on biochemical and performance variables in sled dogs
Authors: Reynolds Arleigh J. , Reinhart Gregory A. , Carey Daniel P. , Simmerman Dawn A. , Frank David A. , Kallfelz Francis A. 
Published: January 2024

Abstract

Objective
To determine effects of protein intake on blood variables, plasma volume, and maximal oxygen uptake (Vo2max) in sled dogs undergoing rigorous training.

Animals
32 Alaskan sled dogs, between 2 and 6 years old.

Procedure
Dogs were assigned to 1 of 4 groups on the basis of age, sex, and ability. Isocaloric diets containing 18% (diet A), 23% (diet B), 29% (diet C), or 35% (diet D) of energy as protein were assigned randomly to each group and fed 1 month before and during a 12-week training period. Maximal oxygen uptake was measured at 0 (before training) and 12 weeks. Body weight, protein and energy intake, plasma volume, PCV, hemoglobin concentration, and serum biochemical variables were measured at 0, 8, and 12 weeks.

Results
Serum biochemical variables, PCV, and hemoglobin concentration remained within reference ranges for all dogs. Dogs fed diet A had a decrease in Vo2max and a greater rate of soft tissue injury throughout training, compared with dogs fed the other diets. At 12 weeks, dogs fed diets C and D had greater serum sodium concentration and hemoglobin concentration than did dogs fed diet A. Dogs fed diet D also had more plasma volume at 12 weeks than did dogs of any other group.

Conclusions and Clinical Relevance
Consumption of a diet with 18% dietary protein on an energy basis (3.0 g of protein/kg of body weight) is insufficient to meet the metabolic requirements of sled dogs in training. For intense interval work, a diet with 35% dietary protein as energy (6.0 g of protein/kg) may provide a performance advantage by promoting an increase in plasma volume. (Am J Vet Res 1999;60: 789–795)
Pharmacokinetics and pharmacologic effects of the S(-) isomer of bupivacaine after intravenous and epidural administration in dogs
Authors: Franquelo Carme , Toledo Alfonso , Manubens Jordi , Valladares J. Enric , Cristòfol Carles , Arboix Margarita 
Published: January 2024

Abstract

Objective
To determine pharmacokinetic variables and pharmacologic effects of the S(-) isomer of bupivacaine (S[-]-BPV) in dogs.

Animals
6 adult male Beagles.

Procedure
Dogs received S(-)-BPV (1 mg/kg of body weight) IV, and 15 days later, the same dogs received 1.8 mg/kg epidurally. Pharmacokinetic variables and pharmacologic effects were determined for each route of administration.

Results
After IV administration, plasma concentration versus time curves were adjusted, using biexponential equations that indicated a rapid distribution phase followed by a slower elimination phase, with a mean ± SD half-life of 33.5 ± 17.0 minutes. Mean plasma clearance was 21.0 ± 10.7 ml/min/kg, and mean volume of distribution at steady state was 0.8 ± 0.2 L/kg. After IV administration, mean peak plasma concentration was 2.6 ± 0.7 µg/ml; after epidural administration, it was 0.9 ± 0.5 µg/ml at approximately 3 minutes. Half-life after epidural administration was 5 times longer than that observed after IV administration. Motor block began immediately after the end of epidural administration and lasted for 3 to 4 hours. Changes in systolic blood pressure and heart rate after epidural administration were slight but occurred at the same time that plasma concentration peaked. After IV administration, motor block or variations in physiologic variables studied were not observed.

Conclusions and Clinical Relevance
In dogs, the pharmacologic behavior of S(-)-BPV was similar to that of the bupivacaine racemate, but motor block attributable to S(-)-BPV lasted longer than that attributable to the racemate, with lower plasma concentrations observed at equivalent sample collection times. (AJVR 1999;60:832–835)
Techniques for evaluation of right ventricular relaxation rate in horses and effects of inhalant anesthetics with and without intravenous administration of calcium gluconate
Authors: Grubb Tamara L. , Constable Peter D. , Benson Gordon J. , Foreman Jonathan H. , Olson William O. , Thurmon John C. , Tranquilli William J. , Davis Lloyd E. 
Published: January 2024

Abstract

Objectives
To determine the most repeatable method for evaluating right ventricular relaxation rate in horses and to determine and compare effects of isoflurane or halothane with and without the added influence of intravenously administered calcium gluconate on right ventricular relaxation rates in horses.

Animals
6 Thoroughbred horses from 2 to 4 years old.

Procedure
6 models (2 for monoexponential decay with zero asymptote, 3 for monoexponential decay with variable asymptote, and 1 for biexponential decay) for determining right ventricular relaxation rate were assessed in conscious and anesthetized horses. The 2 methods yielding the most repeatable results then were used to determine right ventricular relaxation rates in horses anesthetized with isoflurane or halothane before, during, and after IV administration of calcium gluconate. Right ventricular pressure was measured, using a catheter-tip high-fidelity pressure transducer, and results were digitized at 500 Hz from minimum rate of change in ventricular pressure.

Results
2 models that used monoexponential decay with zero asymptote repeatedly produced an estimate for relaxation rate and were used to analyze effects of anesthesia and calcium gluconate administration on relaxation rate. Isoflurane and halothane each prolonged right ventricular relaxation rate, with greater prolongation evident in halothane-anesthetized horses. Calcium gluconate attenuated the anesthesia-induced prolongation in right ventricular relaxation rate, with greater response obtained in isoflurane-anesthetized horses.

Conclusions and Clinical Relevance
Right ventricular relaxation rate in horses is assessed best by use of a monoexponential decay model with zero asymptote and nonlinear regression. Intravenous administration of calcium gluconate to isoflurane-anesthetized horses best preserves myocardial relaxant function. (Am J Vet Res 1999;60:872–879)
Solubilization of liver alkaline phosphatase isoenzyme during cholestasis in dogs
Authors: Solter Philip F. , Hoffmann Walter E. 
Published: January 2024

Abstract

Objective
To determine the mechanism by which liver alkaline phosphatase (LALP) isoenzyme is converted from a membrane-bound enzyme to the soluble enzyme during cholestasis.

Sample Population
Serum and tissues from 2 dogs.

Procedure
The LALP was purified by use of affinity chromatography in samples of serum from dogs with complete bile duct obstruction. Gas chromatography/mass spectrometry was used to detect myo-inositol residues that would be evident when serum LALP had been membrane-attached and released by phospholipase activity. Exclusion chromatography, gel electrophoresis, and octyl-sepharose phase separation of the serum isolate were used to confirm cleavage of the hydrophobic membrane anchor. Western immunoblot analysis was used to distinguish release by glycosylphosphatidylinositol phospholipase D (GPI-PLD) from that by glycosylphosphatidylinositol phospholipase C (GPI-PLC). Intact hepatocytes were incubated with canine serum GPI-PLD to test sensitivity of LALP to release by GPI-PLD. Hepatocyte membrane fragments were treated with serum GPI-PLD and mixtures of taurocholate and taurodeoxycholate to test effects of bile acids on LALP release.

Results
Amounts of myo-inositol per mole of serum LALP isolate were equal to amounts detected with LALP isolated from hepatic tissue. Evaluation of results of western immunoblot analysis and electrophoretic mobility suggested release by GPI-PLD rather than by GPI-PLC. Membrane-bound LALP was resistant to serum GPI-PLD activity in the absence of bile acids; however, incubation in the presence of bile acids caused release of LALP.

Conclusions
Solubilization of LALP during cholestasis involves cleavage of its membrane anchor by endogenous GPI-PLD activity. Action of GPI-PLD is likely enhanced by increased concentrations of hepatic bile acids during cholestasis. (Am J Vet Res 1999;60:1010-1015)
Comparison of sedative effects of romifidine following intravenous, intramuscular, and sublingual administration to horses
Authors: Freeman Sarah L. , England Gary C. W. 
Published: January 2024

Abstract

Objective
To compare sedative effects of romifidine following IV, IM, or sublingual (SL) administration in horses.

Animals
30 horses that required sedation for routine tooth rasping.

Procedure
Horses (n = 10/group) were given romifidine (120 μg/kg) IV, IM, or SL. Heart rate, respiratory rate, head height, distance between the ear tips, thickness of the upper lip, response to auditory stimulation, response to tactile stimulation, and degree of ataxia were recorded every 15 minutes for 180 minutes. Tooth rasping was performed 60 minutes after administration of romifidine, and overall adequacy of sedation was assessed.

Results
IV and IM administration of romifidine induced significant sedation, but SL administration did not induce significant sedative effects. Scores for overall adequacy of sedation after IV and IM sedation were not significantly different from each other but were significantly different from scores for horses given romifidine SL. Sedative and other effects varied among groups during the first 60 minutes after drug administration; thereafter, effects of IV and IM administration were similar.

Conclusions and Clinical Relevance
Onset of action was fastest and degree of sedation was greater after IV, compared with IM, administration of romifidine, but duration of action was longer after IM administration. Sublingual administration did not result in clinically important sedative effects. (Am J Vet Res 1999;60:954-959)
Use of pamidronate to reverse vitamin D3-induced toxicosis in dogs
Authors: Rumbeiha Wilson K. , Kruger John M. , Fitzgerald Scott F. , Nachreiner Raymond F. , Kaneene John B. , Braselton W. Emmett , Chiapuzio Crystal L. 
Published: January 2024

Abstract

Objectives
To determine whether pamidronate di-sodium can reduce vitamin D3-induced hypercalcemia in dogs and whether combination treatment with calcitonin is more effective than treatment with pamidronate alone.

Animals
20 clinically normal male Beagles.

Procedure
All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were assigned randomly to 4 groups of 5 dogs each. Dogs were given 0.9% NaCl solution IV (group 1), calcitonin SC and 0.9% NaCl solution IV (group 2), pamidronate and 0.9% NaCl solution IV (group 3), or a combination of all 3 agents (group 4). Dogs were observed for 28 days, and serial blood and urine samples were collected for determination of serum biochemical, electrolyte, and 25(OH)D3 values, CBC, and urine mineral excretion. Samples of kidney, stomach, lung, aorta, liver, duodenum, and brain were evaluated by light microscopy and quantitative mineral analysis.

Results
Two dogs in group 1 were euthanatized 4 days after CCF administration because of severe clinical signs of disease. Dogs in group 3 lost less weight and had significantly lower serum phosphorus, total and ionized calcium, and urinary zinc concentrations, compared with dogs in group 1. On day 4, serum urea nitrogen concentration was significantly lower in dogs of groups 3 and 4, compared with dogs in group 1. Mild to moderate mineralization of kidneys and stomach were observed in the 2 group-1 dogs euthanatized on day 4.

Conclusions
Pamidronate administration effectively prevents CCF-induced hypercalcemia and mineralization of soft tissues.

Clinical Relevance
Pamidronate is a potentially useful antidote against CCF toxicosis in dogs. (Am J Vet Res 1999;60:1092-1097)
Antibody titer against bovine respiratory syncytial virus in colostrum-fed dairy calves born in various seasons
Authors: van der Poel Wim H. M. , Middel Wiechert G. J. , Schukken Ynte H. 
Published: January 2024

Abstract

Objective
To determine antibody titer against bovine respiratory syncytial virus (BRSV) in dairy calves on farms and to investigate whether passively acquired antibody titers differ in calves born in various seasons.

Sample Population
Serum samples from 129 colostrum-fed replacement calves in 8 dairy herds.

Procedure
A standard ELISA was used to determine BRSV-specific antibodies in serum samples obtained monthly, and antibody titers for calves born in various seasons were compared.

Results
BRSV-specific antibody titer in colostrum-fed dairy calves decreased to undetectable values at 3 to 4 months old. Calves born in winter generally had lower titers, compared with those for calves born in other seasons (P< 0.05). Titers in calves born in seasons other than winter did not differ.

Conclusions and Clinical Relevance
Calves born in winter generally have lower BRSV-specific antibody titers, which may be caused by generally lower antibody titers in colostrum or by factors influencing colostrum intake. (Am J Vet Res 1999;60:1098-1101)
Subconjunctivally implanted micro-osmotic pumps for continuous ocular treatment in horses
Authors: Blair Michael J. , Gionfriddo Juliet R. , Polazzi Lisa M. , Sojka Janice E. , Pfaff Ann M. , Bingaman David P. 
Published: January 2024

Abstract

Objective
To evaluate the feasibility of using a subconjunctivally implanted micro-osmotic pump for continuous delivery of medication to the eyes of horses-during a 7-day period.

Animals
4 healthy adult horses.

Procedure
With horses restrained in a standing position, micro-osmotic pumps were implanted sub-conjunctivally in each eye for 7 days. The treatment eye received an atropine-loaded micro-osmotic pump (100 μl of 1.5% atropine), and the contralateral eye received a sterile saline-loaded pump (100 μl of 0.9% NaCl) as a control treatment. Pupil size was measured at 12-hour intervals until values returned to baseline.

Results
The micro-osmotic pumps were tolerated and did not migrate or become dislodged. During the 7-day treatment period, pupils were significantly larger in the eyes implanted with atropine-loaded pumps, compared with saline-implanted control eyes.

Conclusions and Clinical Relevance
Micro-osmotic pumps were implanted and removed easily from standing horses and were not associated with complications during the 7-day treatment period. Therefore, subconjunctivally implanted micro-osmotic pumps can potentially be used when treating ophthalmic disease in horses. (Am J Vet Res 1999;60:1102-1105)
Identification of a 6 base pair insertion in West Highland White Terriers with erythrocyte pyruvate kinase deficiency
Authors: Skelly Barbara J. , Wallace Mary , Rajpurohit Yashoda R. , Wang Ping , Giger Urs 
Published: January 2024

Abstract

Objective
To define the disease-causing mutation in West Highland White Terriers (WHWT) with erythrocyte pyruvate kinase (R-PK) deficiency and to design a genetic test capable of recognizing affected (homozygous) and carrier (heterozygous) dogs.

Animals
3 anemic WHWT littermates and 1 unaffected littermate; 16 dogs from the same kennel, including 4 unrelated, phenotypically normal dogs (control dogs), and 12 for which PK activity was not known; 2 PK-deficient Basenjis; 2 PK-deficient Beagles; 4 unaffected English Springer Spaniels; and 1 mixed-breed dog.

Procedures
cDNA was cloned and sequenced, and cDNA sequences were compared with the published sequence for canine R-PK cDNA to identify the putative disease-causing mutation. Genomic DNA spanning the affected region was cloned and sequenced to verify the mutation. Subsequently, polymerase chain reaction primers were designed to amplify the section of the gene containing the mutation from DNA in blood or buccal swab samples. Gel electrophoresis allowed assignment of genotypes on the basis of allele separation.

Results
4 single base polymorphisms attributable to sequencing errors in the published sequence were identified, along with a 6 base pair (bp) insertion in exon 10 that was recognized as a putative disease-causing mutation. An identical insertion was found in genomic DNA. Amplification of genomic DNA yielded a 117 bp product for genotypically normal dogs and a 123 bp product for WHWT homozygous for PK deficiency. Carriers had 1 copy of each allele and variable heteroduplex structures.

Conclusions and Clinical Relevance
A 6 bp insertion in the C domain of R-PK was identified in whwt with PK deficiency. Affected and carrier dogs could be distinguished with a genetic test. (Am J Vet Res 1999;60:1169-1172)
Effects of the antimicrobial growth promoter tylosin on subclinical infection of pigs with Salmonella enterica serotype Typhimurium
Authors: Baggesen Dorte L. , Wingstrand Anne , Carstensen Bendix , Nielsen Bent , Aarestrup Frank M. 
Published: January 2024

Abstract

Objective
To determine whether feeding tylosin, an antimicrobial growth promoter, to pigs was associated with increased risk of infection with and excretion of Salmonella enterica serotype Typhimurium.

Animals
117 healthy pigs.

Procedure
A commercial pelleted dry feed was given in 2 feeding trials. In trial A, 11 pigs were given feed with tylosin, 11 pigs were given feed without tylosin, and 11 pigs were given feed with tylosin before and feed without tylosin after inoculation with S Typhimurium. In trial B, 44 pigs were given feed that contained tylosin, and 44 pigs were given feed without tylosin. Three weeks after the start of each trial, pigs were orally inoculated with approximately 5 × 106 colony-forming units of S Typhimurium. Feces were examined for S Typhimurium, using semiquantitative microbiologic techniques before and for 5 or 6 weeks after inoculation. Serum antibody titers against S enterica were measured by use of ELISA.

Results
None of the pigs developed clinical signs of salmonellosis. However, after inoculation, S Typhimurium was isolated from feces of most pigs, and all but 2 pigs developed serum antibodies against S enterica. Significant differences were not detected between experimental and control groups in either trial.

Conclusions and Clinical Relevance
Results indicate that tylosin fed as an antimicrobial growth promoter to pigs may not be an important factor in promoting infection with or excretion of S enterica serotype Typhimurium. (Am J Vet Res 1999;60:1201–1206)
Effect of inhaled nitric oxide on experimentally induced pulmonary hypertension in neonatal foals
Authors: Lester Guy D. , DeMarco Vincent G. , Norman Wendy M. 
Published: January 2024

Abstract

Objective
To evaluate the efficacy of inhaled nitric oxide (NO) in anesthetized healthy newborn foals with experimentally induced pulmonary hypertension.

Animals
Five 1- to 3-day-old foals.

Procedure
Anesthesia was induced and maintained with propofol, and foals were intubated and mechanically ventilated. Systemic pressure and pulmonary arterial pressure (PPA) were recorded every 30 seconds. Hypertension was induced via a hypoxic gas mixture or chemical vasoconstriction, using the thromboxane mimetic U46619. Nitric oxide was added at a concentration of 80 parts per million (ppm) for 6 minutes under baseline conditions and during pulmonary hypertension-induced alveolar hypoxia (inspired oxygen concentration = 0.08). Nitric oxide (20, 40, 80, and 160 ppm) was evaluated during U46619-induced hypertension. Samples for determination of arterial blood gas tensions were collected before and after each NO treatment.

Results
Inhaled NO (approx 80 ppm) did not have an effect on baseline variables. Infusion of U46619 (0.35 ± 0.04 μg/kg of body weight/min) or alveolar hypoxia resulted in increased PPA and decreased arterial oxygenation (Pao2) and hemoglobin saturation (HbSat). The increase in PPA was attenuated, in a dose-dependent manner, by NO during U46619 infusion and reversed by NO during induced hypoxemia. The Pao2 and HbSat were significantly improved at all NO doses during U44619 infusion but not during alveolar hypoxia. For all inhaled NO concentrations, nitrogen dioxide and methoglobin values were < 5 ppm and 3%, respectively.

Conclusions and Clinical Relevance
Nitric oxide is a potent, selective vasodilator of the pulmonary circulation in healthy newborn foals. Inhaled NO may have value as a therapeutic agent in foals with pulmonary hypertension. (Am J Vet Res 1999;60:1207–1212)