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- Author or Editor: A. Morrie Craig x
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Abstract
Objective—To determine the serum concentrations and sedative effects of fentanyl after transdermal administration at 3 dosages in llamas.
Animals—9 healthy adult female llamas (mean age, 8 ± 3 years; mean weight, 150 ± 18 kg).
Procedure—Llamas were allocated to 1 of 3 groups (3 llamas/group). Fentanyl patches (each providing transdermal delivery of 75 µg of fentanyl/h) were placed on shaved areas of the antebrachium of all llamas. In group 1, llamas were treated with 1 patch (anticipated fentanyl dosage, 75 µg/h). In group 2, llamas were treated with 2 patches (anticipated fentanyl dosage, 150 µg/h). In group 3, llamas were treated with 4 patches (anticipated fentanyl dosage, 300 µg/h). For each llama, the degree of sedation was assessed by use of a subjective scoring system and a blood sample was collected for determination of serum fentanyl concentration at 12, 24, 36, 48, 60, and 72 hours after patch placement.
Results—Following the placement of 4 patches, mean ± SD serum fentanyl concentration in group 3 llamas reached 0.3 ± 0.08 ng/mL within 12 hours. This concentration was sustained for 72 hours. In group 2, application of 2 patches provided inconsistent results; in group 1, application of 1 patch rarely provided measurable serum fentanyl concentrations. No llamas became sedated at any time.
Conclusions and Clinical Relevance—Results suggest that application of four 75 µg/h fentanyl patches provides consistent, sustained serum fentanyl concentrations without sedation in llamas. However, the serum concentration of fentanyl that provides analgesia in llamas is not known. (Am J Vet Res 2005;66:907–909)
Abstract
Objective
To establish reference values for blood concentrations of total calcium (Ca), inorganic phosphorus (P), iron (Fe), copper (Cu), zinc (Zn), selenium (Se), and vitamin E (Vit E) in clinically normal llamas.
Animals
270 llamas ranging in age from < 1 month to > 15 years and grouped by age, sex, pregnancy status, and stage of gestation. Selected llamas were from 21 farms in Oregon, did not have previous health problems, and met specific health criteria on examination.
Procedure
Serum and blood samples were obtained and analyzed for concentrations of Ca, P, Fe, Cu, Se, Zn, and Vit E, and total iron binding capacity (TIBC) and percentage of transferrin saturation (% Sat). Mean differences by age, sex, pregnancy status, and stage of gestation, as well as all interactions, were compared to establish reference values.
Results
Mean values and reference ranges for most of the minerals and vitamins were similar to previously reported values. Male versus female differences were not identified for any measurements. Age was a significant variable for Ca, P, Fe, and Se concentrations, as well as Ca-to-P ratio and TIBC. Identified age-based effects were modeled by use of linear regression. Copper and Zn concentrations and % Sat did not differ as a function of age. Serum Vit E concentration was influenced by an age by sex interaction and stage of gestation.
Conclusions
Age was found to be an important variable influencing many blood nutrient concentrations in healthy llamas.
Clinical Relevance
Clinical diagnosis of metabolic disease may be improved with use of age-based reference values, especially for neonates. (Am J Vet Res 1998;59:1063–1070)
Abstract
Objective—To compare hepatic metabolism of pyrrolizidine alkaloids (PAs) between sheep and cattle and elucidate the protective mechanism of sheep.
Sample Population—Liver microsomes and cytosol from 8 sheep and 8 cattle.
Procedure—The PA senecionine, senecionine N-oxide (nontoxic metabolite) and 6,7-dihydro-7-hydroxy- 1-hydroxymethyl-5H-pyrrolizine (DHP; toxic metabolite) were measured in microsomal incubations. The kcat (turnover number) was determined for DHP and N-oxide formation. Chemical and immunochemical inhibitors were used to assess the role of cytochrome P450s, flavin-containing monooxygenases (FMOs), and carboxylesterases in senecionine metabolism. The CYP3A, CYP2B, and FMO concentrations and activities were determined, in addition to the role of glutathione (GSH) in senecionine metabolism.
Results—DHP concentration did not differ between species. Sheep formed more N-oxide, had higher N-oxide kcat, and metabolized senecionine faster than cattle. The P450 concentrations and isoforms had a large influence on DHP formation, whereas FMOs had a large influence on N-oxide formation. In cattle, CYP3A played a larger role in DHP formation than in sheep. FMO activity was greater in sheep than in cattle. Addition of GSH to in vitro microsomal incubations decreased DHP formation; addition of cytosol decreased N-oxide formation.
Conclusions and Clinical Relevance—Hepatic metabolism differences alone do not account for the variation in susceptibility seen between these species. Rather, increased ruminal metabolism in sheep appears to be an important protective mechanism, with hepatic enzymes providing a secondary means to degrade any PAs that are absorbed from the rumen. (Am J Vet Res 2004;65:1563–1572)
Summary
In 2 studies, plasma, erythrocyte, and neutrophil α-tocopherol concentrations were monitored in beef cattle after shipping, handling, and sample collection. On the basis of α-tocopherol results, an additional 2 studies were designed to measure the effects of administration of adrenocorticotropic hormone (acth) and epinephrine on the α-tocopherol concentration in the aforementioned blood constituents and on creatine kinase (ck) activity in Holstein calves.
In the first of these studies, 15 beef cattle that had recently arrived at the feedlot consumed feed supplemented daily with 1,000 IU of dl-α-tocopheryl acetate. Values for initial blood samples indicated that ck activity was high. Although plasma α-tocopherol concentration indicated that vitamin supplementation was adequate, rbc and neutrophil α-tocopherol values were generally nondetectable. After 4 weeks of supplementation, plasma α-tocopherol concentration increased (P < 0.05), and neutrophil and rbc α-tocopherol values became measurable in most of the cattle. In the second study, 6 beef heifers had decreased (P < 0.05) plasma, rbc, and neutrophil α-tocopherol values after multiple periods of handling and blood sample collection.
In the third and fourth studies, 10 tamed Holstein heifer calves, 5 of which were administered acth and epinephrine to simulate stress effects on blood α-tocopherol concentrations and ck activity. In study 3, the vitamin E-adequate heifers had increased blood ck (P < 0.001) activity and cortisol (P < 0.01) concentration, and decreased (P < 0.05) neutrophil α-tocopherol concentration after hormone injections. In study 4, when vitamin E-deficient calves received the aforementioned hormones, ck activity increased (P < 0.05) and rbc α-tocopherol concentration decreased (P < 0.05), whereas plasma and neutrophil values did not change.
These results indicate that shipping and handling, or the stress paradigm of acth and epinephrine injections, may reduce the α-tocopherol content of plasma, rbc, and neutrophils while increasing plasma ck activity, which indicates membrane destruction.
Abstract
Objective—To determine whether iontophoretic administration of dexamethasone to horses results in detectable concentrations in synovial fluid, plasma, and urine.
Animals—6 adult mares.
Procedure—Iontophoresis was used to administer dexamethasone. Treatments (4 mA for 20 minutes) were administered to a tarsocrural joint of each mare. The drug electrode contained 3 ml of dexamethasone sodium phosphate at a concentration of 4 or 10 mg/ml. Samples of synovial fluid, blood, and urine were obtained before and 0.5, 4, 8, and 24 hours after each treatment. All samples were tested for dexamethasone using an ELISA. Synovial fluid also was evaluated for dexamethasone, using high-performance liquid chromatography.
Results—The lower and upper limits of detection for dexamethasone in synovial fluid with the ELISA were 0.21 and 1.5 ng/ml, respectively. Dexamethasone administered at a concentration of 10 mg/ml was detected by the ELISA in synovial fluid of 5 mares from 0.5 to 24 hours and in urine of 4 mares from 0.5 to 8 hours after each treatment, but it was not detected in plasma. Mean synovial fluid concentration of dexamethasone was 1.01 ng/ml. Dexamethasone administered at a concentration of 4 mg/ml was detected by the ELISA in urine of 2 mares at 0.5 and 4 hours after treatment, but it was not detected in synovial fluid or plasma.
Conclusion and Clinical Relevance—Iontophoresis cannot be considered an effective method for delivery of dexamethasone to synovial fluid of horses, because drug concentrations achieved in this study were less than therapeutic concentrations. (Am J Vet Res 2002;63:11–14)
SUMMARY
Serum total bile acid concentrations were determined for various types and ages of cattle. There was extreme variability among all the cattle, but the variance was twice as large (0.50 vs 0.22 in logarithmic scale) for beef cattle than for dairy cattle. There was no significant difference in serum total bile acid concentrations between beef cattle and dairy cattle in midlactation. Values for calves < 6 weeks old and for 6-month-old heifers were significantly (P = < 0.05) lower than values for lactating dairy cows. The 5th to 95th percentile range of values (μmol/L) for beef cattle was 9 to 126; for lactating dairy cattle, 15 to 88; and for 6-month-old dairy heifers, 11 to 64.
SUMMARY
Twelve nonlactating dairy cows, free of signs of liver disease and with normal serum activities of liver-derived enzymes and normal liver biopsy tissue, were examined over a 72-hour period for serum total bile acid concentrations. The cattle were fed hay twice daily, and blood samples were obtained every hour for 24 hours, every other hour for 24 hours, then every hour for 24 hours. After 3 weeks, the study was repeated on 6 of the cattle, thus providing data for eighteen 72-hour periods. Serum bile acid concentration varied greatly over the 72 hours, with the range being from one third to 3 times the median. There were variations by as much as 60 μmol/L from 1 hour to the next. After another 3 weeks, 8 of the cattle were deprived of hay for 48 hours and then fed hay morning and afternoon of the third (last) day of the study. There was no significant reduction in bile acid concentration after withholding the hay, but the variability was reduced (P = 0.02) during the last 20 hours of the hay-deprivation period.
In 3 ancillary studies, serum bile acid concentrations were examined over a 48-hour period in 2 cows in early lactation, 3 cows in midlactation, and two 6-month-old heifers. The cows were fed hay and grain twice daily, and the heifers were fed only hay twice daily. In comparison with values for the 12 nonlactating cows fed hay twice daily, mean serum bile acid concentration in the recently freshened cows was significantly (P < 0.002) higher (62.9 vs 22.0 μmol/L). The cows in midlactation had hourly fluctuations as great as 65 μmol/L. Values for the heifers varied less than values in older cattle.