Evaluation of 3 Assays for Failure of Passive Transfer in Calves

This study examined the sensitivity, specificity, predictive values, and classification accuracy of 3 commonly used screening tests for failure of passive transfer: the sodium sulfite turbidity test, the zinc sulfate turbidity test, and re-fractometry relative to serum immunoglobulin G₁, (IgG₁) concentrations determined by radial immunodiffusion. Serum samples were obtained from 242 calves ranging from 1 to 8 days of age. Using a serum concentration of 1,000 mg/dL IgG₁ to define adequate passive transfer, the zinc sulfate test had a sensitivity of 1.00 and a specificity of 0.52 in the detection of inadequate passive transfer. The endpoint of the test appeared to be higher than desired; calves testing negative had mean serum IgG₁ concentration of 955 mg/dL and a large proportion of calves with adequate passive transfer were misclassified as positive for failure of passive transfer. Using the qualitative zinc sulfate test, the percentage of calves correctly classified with regard to passive transfer status was less than that observed with either the sodium sulfite test or refractometry. The sensitivity of the sodium sulfite assay was 0.85 at a 1+ endpoint and 1.00 at a 2 or 3+ endpoint. The specificity of the sodium sulfite assay varied from 0.87 at a 1+ endpoint and 0.56 at a 2+ endpoint. The sensitivity and specificity of refractometry varied from 0.01 to 1.00 depending on the choice of endpoint. Refractometry correctly classified the largest proportion of calves with regard to their passive transfer status at test endpoints of 5.0 and 5.5 g/dL, 83% and 82% respectively. The highest percentages of calves correctly classified occurred with the sodium sulfite test using a 1+ endpoint (86.30%) and refractometry using a 5.0 g/dL endpoint (83.00%). A regression equation was developed that permitted calculation of an optimal endpoint for refractometric determinations of total serum protein concentration. A serum protein concentration of 5.2 g/dL was equivalent to 1,000 mg/dL serum IgG₁. Optimal selection of tests for passive transfer status in calves will be governed by the prevalence of failure of passive transfer, test performance, and the anticipated costs of classification errors.     

Correlation between the pharmacokinetics of oxindanac and inhibition of serum thromboxane B2 in calves

The pharmacokinetics and pharmacodynamics of the non-steroidal antiinflammatory drug, oxindanac, were assessed simultaneously in calves after intravenous (i.v.) administration at dose rates of 0.5, 1, 2, 4 and 8 mg/kg. Plasma pharmacokinetic data were fitted to either two or three compartment open models. The elimination t ¹/₂ was constant in the dose range 0.5 to 4 mg/kg (20.2–22.8 h) and shorter at 8 mg/kg (14.7 h). The pharmacodynamics of oxindanac were assessed by its inhibition of serum TxB₂, an index of platelet cyclo-oxygenase activity. Plots of total plasma oxindanac concentration vs. inhibition of serum TxB₂ fitted in all cases a sigmoidal E_max equation. There were no significant differences in the estimates for ED ₅₀ (1.6-1.9 μg/ml), Hill constant (1.3-2.7) or Emax between the doses used in the in vivo studies or when blood was spiked with oxindanac in vitro. Plots of inhibition of serum TxB₂ vs. time were prepared from the pharmacokinetic model equations in each calf in combination with a single sigmoidal E_max plot generated in vitro. These data were not significantly different from the results produced in vivo. It is concluded that oxindanac causes reversible inhibition of platelet cyclo-oxygenase in calves. Its inhibition of serum TxB₂ can be predicted from total plasma drug concentration, as described by a multicompartmental model, and sigmoidal E_max enzyme kinetics. It was not necessary to take into account factors such as drug equilibration between plasma and its target site, free vs. total drug concentration or chirality. This simple model may be useful for predicting the pharmacodynamics of oxindanac in other species.     

Oxygen saturation measurements in canine blood containing hemoglobin glutamer-200 (Bovine): in vitro validation of the NOVA CO-Oximeter

Abstract: This study was designed to validate in vitro oxygen saturation (SO₂) measurements with the NOVA CO-Oximeter (Nova Biomedical Corp, Waltham, Mass, USA) in canine blood containing hemoglobin (Hb) glutamer-200 bovine (Hb-200; Oxyglobin, Biopure, Cambridge, Mass, USA) as a Hb-based oxygen carrier recently introduced into clinical practice. In the first set of experiments, stored blood from 6 mixed-breed canine blood donors was used. Target PO₂ levels were reached in aliquots of blood samples by tonometry. Oxygen saturation was then measured with the test device and calculated based on known PO₂ values. In the second set of experiments, total oxygen content was directly measured by means of an oxygen-specific electrode in aliquots of fresh whole arterial, venous, and mixed (arterial-venous) blood withdrawn from the same canine blood donors. Hb-200 was added to those blood samples to yield plasma Hb concentrations of 1.62, 3.25, 6.50, and 9.75 g/dL. Based on Hb content and SO₂ measured by the NOVA CO-Oximeter in these samples, total oxygen content was also calculated for each sample and compared with measured values. A strong correlation was found between SO₂ values measured with the co-oximeter in samples after tonometry, and calculated SO₂ based on known PO₂. Directly measured total blood O₂ content varied by ≤ 5% from values computed based on co-oximeter measurements of Hb content and SO₂. These results did not change with different levels of oxygenation of the samples or different plasma Hb-200 concentrations. In conclusion, the NOVA CO-Oximeter is an accurate analyzer for measurement of SO₂ after Hb-200 administration to canine blood.     

Pharmacokinetics of enrofloxacin in newborn and one-week-old calves

The pharmacokinetic behaviour of enrofloxacin was compared in four one-day-old and four one-week-old calves in order to find out if there were any age-related differences. Mean volume of distribution ( V _d(ss)) and clearance ( Cl ) were significantly smaller in newborn calves: V _d(ss) was 1.8 and 2.3 L/kg, while clearance was 0.19 and 0.39 L/kg.h in newborn and one-week-old calves, respectively. Mean elimination half-life ( t _1/2β) did not differ significantly in newborn and in one-week-old calves: mean t _1/2β was 6.6 h and 4.9 h, respectively. Enrofloxacin was metabolized to ciprofloxacin both by newborn and one-week-old calves, but the maximum concentration ( C _max) of ciprofloxacin was lower and the time when maximum concentration was reached ( t _max) later in newborn calves. We conclude that the dosage of enrofloxacin should be adjusted according to age when administered to very young calves.     

High performance liquid chromatography and pharmacokinetics of the non-steroidal anti-inflammatory drug oxindanac in calves

A high-performance liquid chromatographic method for the determination of the non-steroidal anti-inflammatory drug, oxindanac, in calf plasma is described. Recoveries over the concentration range 0.3 75 to 62.5 μg/ml were 90.2–107.8% with interassay coefficients of variation of 2.1–22.3%. The limit of detection was estimated as 0.10 μg/ml and the limit of quantification calculated to be 0.24 pg/ml in a 1 ml plasma sample. This method was used to establish the pharmacokinetics following intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to calves of oxindanac at a dose rate of 2 mg/kg. The elimination t ¹/₂, was long ( t 1/2 21.2 h after i.v. injection) and absorption was rapid (t¹/_2B 0.072 h) and complete ( F > 100%) following i.m. administration. Bioavailability was incomplete ( F = 66.6%) following p.o. administration to calves that had been fed on milk, and Wagner-Nelson analysis revealed twoabsorption phases ( t ¹/₂'s 0.20 and 1.9 h). Oxindanac produced long-lasting inhibition of serum TxB₂ production, with mean k_max values (% inhibition) of 96.8, 94.1 and 81.3 following i.v., i.m. and p.0. administration, respectively. A single i.v. or i.m. injection of 2 mg/kg oxindanac will probably be active in calves for at least 36–48 h.     

Differential inhibition of cyclooxygenase isoenzymes in the cat by the NSAID robenacoxib

Robenacoxib is a new nonsteroidal anti-inflammatory drug (NSAID) developed for use in companion animal medicine. The objectives of this study were: to quantify the inhibitory actions of robenacoxib on cyclooxygenase (COX) isoenzymes in feline whole blood assays; to establish blood concentration–time profiles of robenacoxib after intravenous and subcutaneous dosing in the cat and; to predict the time courses of inhibition of COX isoforms by robenacoxib. COX-1 and COX-2 activities in heparinized feline whole blood samples were induced with calcium ionophore and lipopolysaccharide, respectively. Inhibition of thromboxane B₂ provided a marker of both COX-1 and COX-2 activities and a nonlinear parametric mixed effects modelling approach was used to establish the pharmacodynamic parameters describing this inhibition. Mean values (and prediction intervals) of IC₅₀ were 28.9 (16.4–51.1) μ m (COX-1) and 0.058 (0.010–0.340) μ m (COX-2). These parameters were used to compute several selectivity indices. Selectivity IC ratios (COX-1:COX-2) were 502.3 (IC₅₀/IC₅₀), 451.6 (IC₉₅/IC₉₅) and 17.05 (IC₂₀/IC₈₀). Based on a clinically recommended dosage regimen of 2 mg/kg, it was predicted that the corresponding mean robenacoxib blood concentration over the first 12 h after drug administration corresponded to 5% inhibition of COX-1 and 90% inhibition of COX-2.     

Growth, weaning performance and blood indicators of humoral immunity in Holstein calves fed supplemental flavonoids

The primary objective was to test the hypothesis that flavonoids mediate immune response and affect calf performance. Twenty Holstein calves [7 ± 2 days age; 41.4 ± 0.7 kg body weight (BW)] were randomly assigned to four treatments of (i) no; (ii) low (7.3 × 10⁻⁵ g/kg BW); (iii) medium (7.3 × 10⁻⁴ g/kg BW); and (iv) high (3.6 × 10⁻³ g/kg BW) doses of flavonoids intake in a completely randomized design. Calves received the treatments as a tablet until weaning or a daily intake of 680 g starter. After weaning, calves received no supplemental flavonoids and monitored until 120 days of age. The flavonoids were extracted from propolis. Treatments did not affect body length, wither height and the severity of scours. At week 5 of age, BW was higher when calves fed the high compared to the low dose of flavonoids. At week 6, calves fed the high dose of flavonoids had higher BW than those fed no or low doses of flavonoids. The serum immunoglobulin G (IgG) concentrations remained lower at the first 3 weeks of the experiment when calves received the low but not the high doses of flavonoids. At week 4, both medium and low doses of flavonoids moderated serum IgG. At week 8, the medium and high but not the low doses of flavonoids lowered serum IgG. At week 6, calves fed high and medium flavonoids doses had lower blood immunoglobulin M (IgM) than control calves. Results suggest that flavonoids affect the humoral immune response and can improve growth in young calves. This response depended on calf age. Future studies are needed to further evaluate the premise that dietary forages or the main source of flavonoids are helpful for a less stressful weaning in the modern calf raising.     

Thiamphenicol pharmacokinetics in beef and dairy cattle

The pharmacokinetics of thiamphenicol were investigated in 10 calves and six lactating cows. It was found that this drug is rapidly absorbed (1 5 min) following intramuscular injection with an absorption rate constant and a bioavailability of 8.7 h^-1 and 84%, respectively. The drug appears to be widely distributed into various body fluids, yielding a volume of distribution (V_d(area)) of approximately 0.9 l/kg. The micro-rate constants indicated that the antibiotic rapidly diffuses into the peripheral compartment (k₁₂ > k₂₁). Elimination from plasma is relatively rapid, with a biological half-life of about 1.75 h. Thiamphenicol appears shortly in milk (15 min) after its intravenous administration, and gives milk to plasma concentration ratios greater than one between 4 and 12 h.     

Duration of Effects of Phenylbutazone on Serum Total Thyroxine and Free Thyroxine Concentrations in Horses

The objectives of this study were to determine if phenylbutazone decreased serum thyroxine (TT₄) and free thyroxine (FT₄) concentrations using radioimmunoassay and equilibrium dialysis techniques in horses, and, if so, an additional objective was to determine the duration of this decreased concentration once phenylbutazone administration was discontinued. Serum TT₄ and FT₄ concentrations were determined before and after administration of 4.4 mg/kg of phenylbutazone IV bid for 5 days. Treatment with phenylbutazone caused a significant decrease in TT₄ and FT₄ concentrations ( P < .05). Serum TT₄ concentration significantly decreased after day 4 of treatment and remained significantly below baseline value for 10 days after discontinuing phenylbutazone administration; it returned to a value not different from the baseline value by the 11th day. Serum FT₄ concentration significantly decreased after day 4 of treatment and remained significantly below the baseline value for only 1 day after phenylbutazone administration was discontinued; it returned to a value not different from the baseline value by the 3rd day after discontinuation of phenylbutazone. These results indicate that serum TT₄ and FT₄ should not be used to evaluate thyroid function in horses receiving phenylbutazone. In addition, results should be interpreted cautiously when phenylbutazone has been administered within 2 days (for FT₄) or within 10 days (for TT₄) of sample collection.     

Comparison of refractometers and test endpoints in the measurement of serum protein concentration to assess passive transfer status in calves

OBJECTIVE: To evaluate 3 refractometers for detection of failure of passive transfer (FPT) of immunity in calves, and assess the effect of refractometric test endpoints on sensitivity, specificity, and proportion of calves classified correctly with regard to passive transfer status. DESIGN: Prospective study. ANIMALS: 90 calves. PROCEDURE: Blood samples were obtained from calves that were < 10 days old. Serum IgG concentration was determined by use of a radial immunodiffusion assay. Accuracy of 3 refractometers in the prediction of serum IgG concentration was determined by use of standard epidemiologic methods and a linear regression model. RESULTS: At a serum protein concentration test endpoint of 5.2 g/dL, sensitivity of each refractometer was 0.89 or 0.93, and specificity ranged from 0.80 to 0.91. For all refractometers, serum protein concentration test endpoints of 5.0 or 5.2 g/dL resulted in sensitivity > 0.80, specificity > 0.80, and proportion of calves classified correctly > 0.85. Serum protein concentrations equivalent to 1,000 mg of IgG/dL of serum were 4.9, 4.8, and 5.1 g/dL for the 3 refractometers. CONCLUSIONS AND CLINICAL RELEVANCE: The refractometers, including a nontemperature-compensating instrument, performed similarly in detection of FPT. Serum protein concentration test endpoints of 5.0 and 5.2 g/dL yielded accurate results in the assessment of adequacy of passive transfer; lower or higher test endpoints misclassified larger numbers of calves.     

An Investigation of the Action of Neutral Protamine Hagedorn Human Analogue Insulin in Dogs with Naturally Occurring Diabetes Mellitus

Background: Neutral Protamine Hagedorn human analogue insulin (Humulin N) is commonly used for treatment of canine diabetes mellitus (DM). However, blood glucose and serum insulin concentrations in Humulin N-treated dogs with naturally occurring DM have not been reported.
Objective: To investigate blood glucose and serum insulin concentrations in the clinical setting of client-owned Humulin N-treated dogs with naturally occurring, well-regulated DM.
Animals: Ten client-owned dogs with naturally occurring, well-regulated DM.
Methods: In this clinical study, blood glucose and serum insulin concentrations were measured when dogs received food and insulin (T₀), at approximately every half hour for the next 2 hours, and then approximately every 2 hours for an additional 8 hours. Insulin duration of action was defined as the number of hours from T₀ to the lowest blood glucose concentration and until blood glucose concentration returned to an interpolated value of 70% of basal blood glucose concentration (Glucose_b).
Results: Mean percent of insulin-induced blood glucose suppression was 49.9 ± 17.1% (median, 46%; range, 29–78%). Insulin duration of action ranged from 4 to 10 hours. Blood glucose concentration increased initially and returned to Glucose_b within 0.6–2.2 hours after T₀ in 5 dogs. This initial blood glucose surge then was followed by blood glucose suppression in all 5 dogs.
Conclusions and Clinical Importance: These results suggest that Humulin N administered SC twice daily is an effective mode of treatment for dogs with naturally occurring DM. Postprandial hyperglycemia is present in some well-regulated diabetic dogs treated with Humulin N.     

Clinical pharmacology of cefixime in unweaned calves

Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC₅₀) of field isolates of Escherichia coli. Salmonella and Pasteurella were 0.10–0.40 μg/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half-life of cefixime after intravenous and oral administration was 3.5–4.0 h, the steady-state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 μg/mL for the milk-fed calves and 1.76 μg/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC₅₀ of the drug for gram-negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.     

Metabolites of Monascus ruber in silages

A total of 233 silages were examined and found that Monascus ruber was present in 43 samples with counts between 1 × 10³ and 9 × 10⁶ colony-forming units (CFU)/g (mean: 2 × 10⁵ CFU/g). Monacolin K_L and the hydroxy acid monacolin K_A were detected by liquid chromatography-mass spectrometry in 45 and 50 of 233 samples at levels ranging from 25–15 600 and 28–65 400  μ g/kg, respectively. Citrinin was found with high-performance liquid chromatography-fluorescence detection (FLD) in 14 (6%) samples, the concentrations varied between 2.4 and 64.2  μ g/kg. The concentrations of citrinin were low and toxic effects are not anticipated. Monacolin K_A and monacolin K_L occur frequently and in considerable amounts in silages. These metabolites are believed to influence the metabolic activity of rumen anaerobic fungi resulting in a poorer digestion of crude fibre.     

Biomarkers of inflammation in cattle determining the effectiveness of anti-inflammatory drugs

Myers, M. J., Scott, M. L., Deaver, C. M., Farrell, D. E., Yancy, H. F. Biomarkers of inflammation in cattle determining the effectiveness of anti-inflammatory drugs. J. vet. Pharmacol. Therap. 33 , 1–8.
The impact of nonsteroidal anti-inflammatory drugs (NSAID) on prostaglandin E₂ (PGE₂) production and cyclooxygenase 2 (COX-2) mRNA expression in bovine whole blood (WB) cultures stimulated by lipopolysaccharide (LPS) was determined, using the blood from six Holstein dairy cattle in various stages of lactation. Peak production of PGE₂ occurred 24 h after LPS stimulation but did not result in detectable concentrations of thromboxane B₂ (TXB₂). The NSAID indomethacin, aspirin, flunixin meglumine, and 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide (PTPBS; celecoxib analogue), along with dexamethasone, were all equally effective in reducing the concentration of PGE₂ in the bovine WB culture supernatants. Bradykinin exhibited peak supernatant concentrations 1 h after LPS stimulation. Dexamethasone and the NSAID used in this study were equally effective at inhibiting bradykinin production. Peak induction of COX-2 mRNA occurred 3 h post-LPS stimulation. However, neither dexamethasone nor any of the NSAID used in this study altered COX-2 mRNA concentrations. In contrast, aspirin, flunixin meglumine, and PTPBS reduced tumor necrosis factor-alpha (TNFα) mRNA concentration. These results demonstrate that bovine blood cells respond to NSAID therapy like other mammalian cells with respect to inhibition of PGE₂ production and suppression of TNF mRNA induction, but do not inhibit induction of COX-2 mRNA.     

A Simple Apparatus for Frequent Measurement of Gastrointestinal Intraluminal PCO2

The accuracy and precision of an end-tidal infrared CO₂ monitor and customized capnography tubing system designed to measure gastrointestinal intraluminal CO₂ partial pressure (P_iCO₂) were tested in vitro. Samples were taken from the customized capnography tubing placed in either 5% or 10% CO₂ gas at discrete intervals ranging from one minute to twelve minutes. For a given time interval, the tubing PCO₂ measurement was a constant fraction of the actual PCO₂ (all standard errors < 0.02). For increasing time intervals, the ratio of the tubing PCO₂ to actual PCO₂ increased logarithmically. In the 5% and 10% CO₂, the regression coefficients were 0.89 and 0.85 for 8 French tubing and 0.99 and 0.91 for 6 French tubing. Beacuase of its accuracy and precision, this system may provide automated gastrointestinal CO₂ partial pressure monitoring at short intervals (e.g. 5 minutes), facilitating testing of the role of gastrointestinal P_iCO₂ information in treatment algorithms. (Vet Emerg & Crit Care, 1998; 8: 109–116)     

The 14-3-3 cerebrospinal fluid immunoassay lacks utility in the diagnosis of clinical scrapie.

This study determined whether the immunoassay for cerebrospinal fluid 14-3-3 protein concentration was sensitive and specific in the diagnosis of naturally occurring clinical scrapie in sheep. Cerebrospinal fluid was collected from 9 sheep with the confirmed diagnosis of scrapie. Additionally, cerebrospinal fluid was collected from 13 clinically normal sheep, which originated from a closely monitored flock with no history of scrapie. Sensitivity and specificity were calculated using standard epidemiological methods. Cerebrospinal fluid immunoassay results did not differ significantly between positive and negative sheep. Test sensitivity varied from 0.55 to 0.66, depending on the choice of test endpoint. Test specificity varied from 0.30 to 0.77, depending on the choice of test endpoint. The 14-3-3 cerebrospinal fluid immunoassay appears to have no value in the diagnosis of clinical scrapie in sheep.     

A comparison of the various routes of administration of erythromycin in cattle

A comparison of i.v., i.m. and s.c. administration erythromycin base in polyethylene glycol at 15 mg/kg and 30 mg/kg body weight was carried out in beef-type calves of approximately 200 kg body weight. Additional evaluations were carried out with oral administration of erythromycin phosphate and erythromycin stearate. Absorption of erythromycin was very slow by both the i.m. and s.c. routes of administration with a K_ab of 0.0135 min^-1 and 0.0185 min^-1 for i.m. and 0.0032 min^-1 and 0.0074 min^-1 for s.c. at 15 mg/kg and 30 mg/kg, respectively. The bioavailability (32–42%) and peak serum concentrations were much lower with s.c. than with i.m. (60–65%) administration. The disposition of erythromycin administered i.v. appeared to be representative of dose-dependent kinetics rather than dose-independent first-order kinetics inasmuch as the elimination half-time ( t _1/2B) increased from 174.5 ± 13 min for the 15 mg/kg dosage to 239 ± 10.8 min with 30 mg/kg dosage. An acute apparent cardiovascular effect accompanied i.v. administration of erythromycin at 30 mg/kg dosage but not at 15 mg/kg. Severe diarrhea followed oral administration of either erythromycin phosphate or erythromycin stearate.     

Concentrations of thyroid hormones and iodothyronine binding proteins in serum of the koala (Phascolarctos cinereus)

Objective To examine circulating total and free thyroid hormone (T₃ and T₄) concentrations, determine serum iodothyronine binding characteristics and estimate thyroid stimulating hormone (TSH) activity in sera of coastal and inland koalas.
Design A prospective study.
Procedure Koala serum T₃ and T₄ were measured by radioimmunoassay. T₄ binding parameters were determined by radioligand binding and electrophoresis. Koala TSH values were determined by bioassay.
Results Mean total T₄ concentrations were 3.2 ± 2.1 nM although values were significantly higher in inland-dwelling females in comparison to coastal-dwelling males. Free T₄ was 3.3 ± 2.1 pM. Total and free T₃ were 0.4 ± 0.2 nM and 1.4 ± 0.9 pM respectively, although these values were at the lower end of the assay detection limit and should be viewed with reservation. Electrophoresis of [¹²⁵I]-T₄-labelled serum revealed only two proteins of electrophoretic mobility similar to human transthyretin (TTR) and albumin. Scatchard analysis of T₄ binding to serum gave a curvilinear plot, which could be resolved into two binding sites with affinities identical to that of TTR and albumin but both of low concentration. The bioactivity of the TSH present in the sera was measured using a cell line (JP09) transfected with the human TSH receptor. The mean level of stimulation found in the sera corresponded to a bovine TSH activity of less than 10 mU/L.
Conclusion These results suggest that the serum concentrations of free and total thyroid hormones in koalas are low compared to other marsupials and very low compared to eutherian mammals. The mechanism of maintenance of euthyroidism in this species remains to be determined.     

The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1α and ex vivo endotoxin-induced tumour necrosis factor activity in horses

Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F_1α were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2± 1.4 and 7.8± 4.3 μg/mL, respectively. The half-life of elimination ( t _½β) of pentoxifylline was 1.44 h and volume of distribution ( V d_area) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F_1α increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F_1α and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.     

Disposition and bioavailability of neomycin in Holstein calves

Pedersoli, W.M., Ravis, W.R., Jackson, J., Shaikh, B. Disposition and bioavailability of neomycin in Holstein calves. J. vet. Pharmacol. Therap. 17 , 5–11.
The disposition and absorption kinetics of neomycin were studied in healthy ruminating dairy calves ( n -6), approximately 3-months-old. The calves were treated with single intravenous (i.v.) (12 mg/kg), intramuscular (i.m.) (24mg/kg), oral (p.o.) (96 mg/kg) and repeated p.o. (96 mg/kg, b.i.d., 15½ days) doses of neomycin. A 3-week rest period was allowed between treatments A and B and B and C Baseline and serial venous blood samples were collected from each calf plasma concentrations of neomycin were determined by a high performance liquid chromatography procedure. The resulting data were evaluated by using compartmental pharmacokinetic models and nonlinear least squares regression analysis. The mean of some selected parameters were t ½λ3 7.48 ± 2.02 h, Cl_t= 0.25 ± 0.04 L/h/kg, V _d(ss)= 1.17 ± 0.23 L/kg, and MRT = 4.63 ± 0.87 h for the i.v. data and t _½= 11.5 ± 3.8 h, MRT _abs= 0.960 ± 1.001 h, F = 127 ± 35.2%, and Cl_t/F = 0.199 ± 0.047 L/h/kg for the i.m. data, respectively. Only one calf absorbed neomycin to any significant degree (F = 0.0042) after a single p.o. dose. Selected mean parameters determined after repeated oral dosing were: F = 0.45 ± 0.45%, C_max= 0.26 ± 0.37 g/ml, and t_max= 2.6 ± 2.9 h. Terminal half-lives determined for the i.v. and i.m. treatments were considerably longer than those reported previously in the literature.