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  • Author or Editor: Dwayne W. Hamar x
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Abstract

Objective—To determine and compare substrate specificity and kinetic rate constants of feline and canine alcohol dehydrogenase (ADH) with ethanol (EtOH) and ethylene glycol (EG) as substrates in vitro, with and without fomepizole.

Sample Population—Livers from 3 dogs and 3 cats.

Procedure—Canine and feline ADH activity, in cytosolic fractions of homogenized liver, was determined by use of various concentrations of nicotinamide adenine dinucleotide (NAD), EtOH, or EG as substrates. Initial reaction velocities were calculated, and kinetic inhibition rate constants (Ki) for fomepizole were determined.

Results—Substrate specificity of canine and feline ADH for EtOH or EG was not significantly different. A 2-fold difference was detected in the maximal velocity of canine, compared with feline, ADH, using either substrate. Fomepizole Ki in feline hepatic homogenates was significantly greater than Ki in canine hepatic homogenates when either EtOH or EG was used as substrate (10- and 30-fold, respectively). A 6-fold increase in the concentration of fomepizole was required to achieve ADH inhibition, with feline homogenates equivalent to those of canine homogenates.

Conclusions and Clinical Relevance—Feline ADH has lower enzymatic capacity for turnover or is less concentrated in liver than canine ADH with regard to EtOH and EG catalysis. Canine ADH was more effectively inhibited by fomepizole than feline ADH. Results suggest that higher dosages of fomepizole may be more effective to treat cats with EG intoxication than dosages reported to treat dogs. (Am J Vet Res 2000;61:450–455)

Full access
in American Journal of Veterinary Research

Summary

The efficacy of 4-methylpyrazole (4-mp) and ethanol as treatment for ethylene glycol (eg) intoxication in cats was compared. Twenty-two cats were assigned at random to 6 experimental groups. Cats of 1 experimental group were given only 4-mp; those of another experimental group were given only eg. Cats of 3 experimental groups were intoxicated with eg and given 4-mp at 0 hour or 2 or 3 hours after eg ingestion, and those of 1 experimental group were given eg and treated with ethanol 3 hours after eg ingestion. Physical, biochemical, hematologic, blood gas, serum and urine eg concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, and 72 hours, 1 week, and 2 weeks after eg ingestion or 4-mp treatment in cats of the 4-mp only group. The half-life of eg and percentage of ingested eg excreted unchanged were determined for each group.

4-Methylpyrazole treatment at 0 hour was most effective at preventing metabolism of eg. 4-Methylpyrazole was not effective in preventing development of renal failure when given 2 or 3 hours after eg ingestion. Ethanol given 3 hours after eg ingestion was successful in preventing development of renal dysfunction in 2 of the 6 cats treated 3 hours after eg ingestion. Of the remaining 4 cats treated with ethanol, 2 developed transient renal dysfunction and 2 developed acute oliguric renal failure and were euthanatized.

4-Methylpyrazol given 2 or 3 hours after eg ingestion was less effective in preventing eg metabolism than was ethanol given 3 hours after eg ingestion. Therefore 4-mp, at the dose found to be effective in dogs, cannot be recommended as an alternative to ethanol for treatment of eg intoxication in cats.

Free access
in American Journal of Veterinary Research

Summary

4-Methylpyrazole (4-mp), an alcohol dehydrogenase inhibitor, was administered to dogs to treat ethylene glycol (eg) intoxication. Eleven dogs were given 10.6 g of eg/kg of body weight; 5 dogs were treated with 4-mp 5 hours after eg ingestion and 6 dogs were treated with 4-mp 8 hours after eg ingestion. 4-Methylpyrazole was administered iv as a 50-mg/dl solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 12 hours after initial dose, 15 mg/kg; at 24 hours after initial dose, 10 mg/kg; and at 30 hours after initial dose, 5 mg/kg. Physical, biochemical, hematologic, blood gas, serum and urine eg concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 hours, and at 1 week and 2 weeks after eg ingestion.

Dogs of both groups developed clinicopathologic signs associated with eg intoxication, including cns depression, hyperosmolality, high anion gap metabolic acidosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria. Fractional excretion of sodium was increased in all dogs between 1 and 9 hours after eg ingestion, but remained increased beyond 24 hours only in the 2 dogs treated at 8 hours after eg ingestion that developed acute renal failure. All dogs treated 5 hours after eg ingestion recovered without morphologic, biochemical, or clinical evidence of renal impairment. Of the 6 dogs treated 8 hours after eg ingestion, 2 developed acute renal failure. One of the dogs treated 8 hours after eg ingestion remained isosthenuric for 2 months, but did not manifest any other signs of renal impairment. Of the dogs treated 8 hours after eg ingestion, 3 recovered without morphologic, biochemical, or clinical evidence of renal impairment. Serum half-life of eg was prolonged in the dogs treated 8 hours after eg ingestion. Percentage of eg excreted unchanged was 84 ± 2% in the dogs treated 5 hours after eg ingestion, and was 40 ± 10% in the dogs treated 8 hours after eg ingestion. 4-Methylpyrazole was effective in preventing renal failure in all dogs given 10.6 g of eg/kg when treatment was initiated by 5 hours after eg ingestion, and in 4 of 6 dogs when treatment was initiated by 8 hours after eg ingestion.

Free access
in American Journal of Veterinary Research

Summary

Zoometric measurements and bioelectrical impedance analysis were evaluated as methods of body composition determination in healthy cats. Zoometric and impedance measurements were taken on 22 anesthetized adult cats of various ages, genders, breeds, and body weights. The cats were then euthanatized. The bodies were processed through a tissue homogenizer and free-catch specimens were taken, freeze-dried, and analyzed for total body water, protein, fat, potassium, and ash content. Stepwise regression analysis was implemented to identify statistically significant relationships between the chemically determined dependent variables (total body water, protein, potassium, fat-free mass, fat mass, and percent body fat) and the zoometric measurements, with or without bioelectrical impedance analysis. Statistical analysis revealed high correlations between the dependent variables and the corresponding predicted values of those variables. Body weight alone was a poor predictor of body composition in these cats. On the basis of these findings, we suggest that zoometric and bioelectrical impedance measurements may serve as practical, noninvasive, simple, and accurate methods for estimating body composition in domestic cats.

Free access
in American Journal of Veterinary Research

Summary

Nine 115- to 180-kg, hay-adapted, Holstein steers were fed an experimental diet with added sodium sulfate that induces polioencephalomalacia (pem). Five calves developed the disease. Thiamine concentrations in blood, csf, brain, and liver were not indicative of thiamine deficiency. The odor of hydrogen sulfide in eructated rumen gas was associated with the onset of pem. Sulfide concentrations in rumen fluid were measured 1 or 2 times a week by 2 techniques. Sulfide concentrations progressively increased in all 9 calves after the feeding of the pem-inducing diet commenced. The highest concentrations coincided with the onset of clinical signs of pem and were significantly higher in the calves that developed pem than in those that did not. This suggests that pem can result from sulfide toxicosis following excess production of sulfide in the rumen.

Free access
in American Journal of Veterinary Research

SUMMARY

Polioencephalomalacia (pem) was induced in calves by feeding a semipurified, low-roughage diet of variable copper and molybdenum composition. Two formulations resulting in Cu-insufficient and Cu-sufficient forms of the diet were fed (n = 10 and 4 calves, respectively); both diets induced pem. Clinical signs of disease developed as early as 15 days after transition to the experimental diets and included impaired vision, decreased response to external stimuli, and abnormal gait. Grossly evident cerebrocortical lesions consisted of laminar areas of cavitation and/or autofluorescence seen under uv illumination. Hepatic Cu concentration was decreased in calves fed the Cu-insufficient diet, but not below normal range. During the course of feeding either diet, rumen pH decreased, rumen volatile fatty acid concentrations increased, rumen and blood lactic acid concentrations increased, and rumen and plasma thiamine concentrations increased. The thiamine pyrophosphate effect on erythrocyte transketolase activity was unaltered in calves of either diet group. This nutritionally induced form of pem does not appear to be related to Cu deficiency or reduction in plasma or rumen thiamine concentration.

Free access
in American Journal of Veterinary Research

Summary

Although low plasma taurine concentrations have been associated with congestive cardiomyopathy in cats, the cause of taurine depletion in cats consuming adequate quantities of taurine is unknown. Taurine depletion and cardiovascular disease (cardiomyopathy and thromboembolism) developed unexpectedly in 3 of 6 healthy adult cats during a potassium-depletion study. Plasma taurine concentration decreased significantly (P < 0.05) and rapidly over an 8-week period (from 98 to 36 nmol/ml) in 6 cats that consumed a potassium-deficient diet (0.20% potassium, dry matter basis) that was acidified with 0.8% ammonium chloride, despite containing dietary taurine concentrations (0.12% dry matter basis) in excess of amounts currently recommended. Taurine concentrations were significantly lower in cats fed the acidified diet than in 6 cats fed a potassium-deficient diet that was not acidified (36 nmol/ml vs 75 nmol/ml) after 8 weeks. In addition, plasma taurine concentrations did not decrease over a 6-month period in 8 cats that were fed a potassium-replete diet with acidifier. Plasma taurine concentrations were lowest in 3 cats that died of cardiovascular disease in the group receiving potassium-deficient, acidified diets. These data indicated an association between taurine and potassium balance in cats and suggested that development of taurine depletion and cardiovascular disease may be linked to concurrent potassium depletion.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To assess heritability and mode of inheritance for hereditary equine regional dermal asthenia (HERDA) in Quarter Horses.

Animals—1,295 horses with Quarter Horse bloodlines, including 58 horses affected with HERDA.

Procedure—Horses were classified as affected or unaffected or as undetermined when data were insufficient to assess phenotype. Pedigree data were analyzed to determine the probable mode of inheritance. Heritability was estimated by use of Bayesian statistical methods.

Results—Heritability (mean ± SD) of HERDA was estimated to be 0.38 ± 0.13, with both sexes having an equal probability of being affected. Results for evaluation of the pedigrees were consistent with a single Mendelian autosomal recessive mode of inheritance.

Conclusions and Clinical Relevance—HERDA in Quarter Horses is an inherited disease, and affected horses are more likely to produce affected offspring. An autosomal recessive mode of inheritance should be considered by people making breeding decisions involving Quarter Horses when a first-degree relative has been confirmed with HERDA or has produced affected offspring. In addition, breeders whose horses have produced affected offspring can reduce the likelihood of producing affected horses in the future by avoiding inbreeding. (Am J Vet Res 2005;66:437–442)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To analyze the sulfur content of water and forage samples from a geographically diverse sample of beef cow-calf operations in the United States and to estimate frequency and distribution of premises where forage and water resources could result in consumption of hazardous amounts of sulfur by cattle.

Design—Cross-sectional study.

Sample Population—709 forage samples from 678 beef cow-calf operations and individual water samples from 498 operations in 23 states.

Procedure—Sulfur content of forage samples and sulfate concentration of water samples were measured. Total sulfur intake was estimated for pairs of forage and water samples.

Results—Total sulfur intake was estimated for 454 pairs of forage and water samples. In general, highest forage sulfur contents did not coincide with highest water sulfate concentrations. Overall, 52 of the 454 (11.5%) sample pairs were estimated to yield total sulfur intake (as a percentage of dry matter) ≥ 0.4%, assuming water intake during conditions of high ambient temperature. Most of these premises were in north-central (n = 19) or western (19) states.

Conclusions and Clinical Relevance—Results suggest that on numerous beef cow-calf operations throughout the United States, consumption of forage and water could result in excessively high sulfur intake. All water sources and dietary components should be evaluated when assessing total sulfur intake. Knowledge of total sulfur intake may be useful in reducing the risk of sulfur-associated health and performance problems in beef cattle. (J Am Vet Med Assoc 2002;221:673–677)

Full access
in Journal of the American Veterinary Medical Association

Objective—

To evaluate safety and efficacy of 4-methylpyrazole (4-MP) treatment in dogs and to determine clinical signs and outcome of, and clinicopathologic abnormalities in, dogs treated in early or late stages of ethylene glycol (EG) intoxication.

Design—

Retrospective study.

Animals—

107 dogs.

Procedure—

For dogs treated with 4-MP, 1 of 2 dosage regimens was usually used: 20 mg/kg of body weight, IV, initially, 15 mg/kg 17 hours later, and 5 mg/kg 25 and 36 hours after the initial dose, or 20 mg/kg, IV, initially, 15 mg/kg 12 and 24 hours later, and 5 mg/kg 36 hours after the initial dose.

Results—

Neither adverse clinical signs nor clinicopathologic abnormalities were associated with the administration of 4-MP except in 1 dog, which developed tachypnea, gagging, excess salivation, and trembling after the second dose of 4-MP was given. Ethylene glycol intoxication was confirmed in 37 dogs. Of these, 21 were azotemic or became azotemic within 18 hours after admission, and only 1 of the 21 survived. All 16 dogs that did not become azotemic survived. Median time from EG ingestion to treatment with 4-MP was 5 hours (range, 2 to 8.5 hours) for dogs that were not azotemic at admission and 14.5 hours (range, 8.5 to 38 hours) for dogs that were azotemic at admission.

Clinical Implications—

4-MP was a safe and effective treatment for EG intoxication when it was given before sufficient quantities of EG had been metabolized to induce renal failure. Dogs treated within 8 hours of EG ingestion had a good prognosis. (J Am Vet Med Assoc 1996;209:1880–1883)

Free access
in Journal of the American Veterinary Medical Association