Due to the widespread occurrence of acrylamide in the environment, its likely carcinogen status, and the suitability of the pig model as a human analogue, the authors decided to evaluate the impact of high and low doses of this compound on the processes of erythropoiesis in swine bone marrow. The experiment was carried out on Danish Landrace pigs at the age of eight weeks and body weight about 20 kg. The animals were divided into three equal groups consisting of five pigs in each. Control animals received empty gelatin capsules (placebos). Animals from the first experimental group received a low dose of acrylamide of 0.5 μg/kg b.w./day (> 99% purity; Sigma-Aldrich, Poland), and animals from the second experimental group received a dose 10 times higher. Placebos and acrylamide capsules were administered with feed every morning for 28 days. After anaesthetisation of the animals, bone marrow from the femur was collected into tubes without an anticoagulant on days 0 and 28. After drying and staining, bone marrow smears were subjected to detailed cytological evaluation using a light microscope. This study showed that high and low doses of acrylamide affected the process of porcine erythropoiesis. The cytotoxic effect of acrylamide on this process was demonstrated in a change of the polychromatic erythroblasts/normochromatic erythroblasts ratio. Both doses of acrylamide caused a decrease in the number of ortho- and polychromatic erythroblasts.

The objective of this research was to evaluate the antibody response to multiple doses of an inactivated mixed vaccine against Histophilus somni, Pasteurella multocida, and Mannheimia haemolytica, and to investigate the influence of age at time of vaccination in the field. Healthy female Holstein calves received the vaccine at the age of 5–12 days and 2, 3, or 4 weeks later in the first experiment or at 1, 2, or 3 weeks of age and 4 weeks later in the second. Blood samples were collected at each vaccination and 3 weeks after the booster dose. Based on the antibody titres after the vaccinations, calves were divided into positive and negative groups for each of the bacteria. Calves in the control group were vaccinated only once at the age of 19–26 days. Antibody titres against H. somni and P. multocida were significantly increased by the booster. After the second vaccinations, the titres against each bacterium were higher than those of the control group, and the M. haemolytica-positive percentage in calves with high maternal antibody levels (MAL) exceeded that in calves with low MAL. In the first experiment, a majority of the M. haemolytica-positive calves tended to have received the primary dose at seven days of age or older. A booster dose of the inactivated bacterial vaccine in young Holstein calves increased antibody production and overcame the maternal antibodies. Calves should be vaccinated first at seven days of age or older.

Objective-To investigate effects of isoflurane at approximately the minimum alveolar concentration (MAC) on the nociceptive withdrawal reflex (NWR) of the forelimb of ponies as a method for quantifying anesthetic potency. Animals-7 healthy adult Shetland ponies. Procedure-Individual MAC (iMAC) for isoflurane was determined for each pony. Then, effects of isoflurane administered at 0.85, 0.95, and 1.05 iMAC on the NWR were assessed. At each concentration, the NWR threshold was defined electromyographically for the common digital extensor and deltoid muscles by stimulating the digital nerve; additional electrical stimulations (3, 5, 10, 20, 30, and 40 mA) were delivered, and the evoked activity was recorded and analyzed. After the end of anesthesia, the NWR threshold was assessed in standing ponies. Results-Mean +/- SD MAC of isoflurane was 1.0 +/- 0.2%. The NWR thresholds for both muscles increased significantly in a concentration-dependent manner during anesthesia, whereas they decreased in awake ponies. Significantly higher thresholds were found for the deltoid muscle, compared with thresholds for the common digital extensor muscle, in anesthetized ponies. At each iMAC tested, amplitudes of the reflex responses from both muscles increased as stimulus intensities increased from 3 to 40 mA. A concentration-dependent depression of evoked reflexes with reduction in slopes of the stimulus-response functions was detected. Conclusions and Clinical Relevance-Anesthetic-induced changes in sensory-motor processing in ponies anesthetized with isoflurane at concentrations of approximately 1.0 MAC can be detected by assessment of NWR. This method will permit comparison of effects of inhaled anesthetics or anesthetic combinations on spinal processing in equids.

Objective-To measure effects of Escherichia coli O149:F4-induced diarrhea on water consumption and pharmacokinetics of amoxicillin after administration in drinking water. Animals-24 recently weaned 24- to 28-day-old crossbred pigs. Procedure-10 pigs were inoculated with E coli O149:F4; all 10 pigs subsequently developed diarrhea. Pigs were medicated by administration of amoxicillin in the drinking water (0.75 mg/mL) for a 4-hour period on 2 consecutive days. Fourteen age-matched noninfected healthy pigs (control group) were medicated in a similar manner. Blood samples were obtained from both groups daily, and plasma concentrations of amoxicillin were analyzed by use of high-performance liquid chromatography. Results-Diarrhea reduced the area under the plasma concentration-versus-time curve (AUC) and maximum plasma concentration (C(max)) of amoxicillin on the first day of medication by 56% and 63%, respectively. The AUC of amoxicillin on the second day of medication for diarrheic pigs did not differ significantly from that of control pigs on the first day of medication. Conclusions and Clinical Relevance-E coli-induced diarrhea reduced the AUC of amoxicillin and time that plasma concentration of amoxicillin was > 0.025 microgram/mL and, hence, less likely to have a therapeutic effect on the first day of administration in drinking water. On the assumption that plasma concentrations may indirectly reflect concentrations at the site of infection, analysis of our results suggests that higher doses of amoxicillin may be appropriate for administration in drinking water during a 4-hour period on the first day that pigs have diarrhea attributable to E coli O149:F4.

Chickens (n = 18), ranging in age from 30 to 50 weeks and in body weight from 1.1 to 2.1 kg, were anesthetized with isoflurane. Ventilation was controlled, and temperature was maintained at 40.1 +/- 1.0 C. The minimal anesthetic concentration (MAC) of isoflurane was determined by use of a bracketing technique based on purposeful movement in response to a toe clamp. After determining isoflurane MAC in triplicate, birds were given a mu-opioid agonist (morphine, n = 9) or a kappa-opioid agonist (U50488H, n = 9). Determination of MAC was repeated after each IV administration of agonist in progressive doses of 0.1, 1.0, and 3.0 mg/kg of body weight. Heart rate and mean arterial blood pressure (MAP) were recorded immediately before and after each injection. Control MAC (mean +/- SEM) was 1.24 +/- 0.05% and 1.05 +/- 0.03% for the mu- and kappa-opioid agonist groups, respectively. Morphine and U50488H caused a dose-dependent decrease in isoflurane MAC in all birds. Reduction of MAC from control (mean +/- SEW) was 15.1 +/- 2.7, 39.7 +/- 3.1, and 52.4 +/- 4.0% after the 3 successive doses of morphine and was 13.3 +/- 3.0, 27.6 +/- 3.3, and 40.8 +/- 3.8% after U50488H was given. Each opioid injection resulted in significant (P less than or equal to 0.05, repeated measures ANOVA) lowering of MAC. Heart rate and MAP did not change significantly (P less than or equal to 0.05, paired Student's t-test) after any dose of opioid. In conclusion, morphine or U50488H decreased isoflurane MAC in dose-dependent manner without significant effect on heart rate and MAP.

Once-daily administration of aminoglycosides may be a safe and effective therapeutic regimen, on the basis of the microbiologic and pharmacokinetic characteristics of these antibiotics. This study was designed to determine serum and tissue concentrations following IV administration of gentamicin, at dosages of 6.6 mg/kg of body weight, every 24 hours, and 2.2 mg/kg, every 8 hours, for 10 days in adult horses. Nephrotoxicosis from these dosage regimens also was compared, and microbiologic effects, including postantibiotic effects, were determined with various concentrations of gentamicin against an equine clinical isolate of Pseudomonas aeruginosa. Treatment at the 6.6-mg/kg dosage resulted in maximal serum concentrations (77.93 +/- 19.90 micrograms/ml, mean +/- SEM) and area under the concentration-vs-time curves (83.79 +/- 14.97 micrograms.h/ml) that were significantly (P < 0.05) greater than those following treatment at the 2.2-mg/kg dosage (5.05 +/- 0.50 micrograms/ml and 6.03 +/- 0.66 micrograms.h/ml, respectively). Nephrotoxicosis was not induced with either dosage regimen, and postantibiotic effects were prolonged with a higher gentamicin concentration. This study provided evidence to support the use of once-daily gentamicin treatment in adult horses.

A cross-over study was performed in 6 healthy mixed-breed dogs and 4 healthy Beagles. Diazepam was administered per rectum to Beagles (0.5 mg/kg of body weight) and mixed-breed dogs (2 mg/kg), and IV (0.5 mg/kg) to both groups of dogs. Each dog received the drug by both routes, with a 1-week washout period between dosages. After diazepam administration, blood samples were collected to measure plasma concentration of diazepam and its active metabolites, desmethyldiazepam and oxazepam, by use of reverse-phase high-performance liquid chromatography (HPLC). Systemic availability was assessed by comparing the area under the curve for diazepam metabolites for each route of administration. Mean (+/- SD) diazepam concentrations in plasma after rectal administration were low in comparison with those obtained after IV administration, with systemic availability of only 7.4 (+/- 5.9) and 2.7 (+/- 3.2)% for the high and low dose, respectively. However, diazepam was converted to its metabolites within minutes after administration. Accounting for the total concentration of benzodiazepines (diazepam plus desmethyldiazepam and oxazepam) in plasma, systemic availability was 79.9 (+/- 20.7) and 66.0 (+/- 23.8)% for the high and low dosage, respectively. After IV administration, diazepam concentration decreased, with a half-life of only 14 to 16 minutes, but desmethyldiazepam and oxazepam concentrations decreased more slowly, with a half-life of 2.2 to 2.8 hours and 3.5 to 5.1 hours, respectively. Each of the metabolites is reported to have anticonvulsant activity. After rectal administration of the high dose, mean total benzodiazepine concentration was above 1.0 micrograms/ml within 10 minutes and was maintained above this concentration for at least 6 hours. We conclude that diazepam is absorbed after rectal administration in dogs, and that the pharmacologic effects are probably caused by the active metabolites, not the parent drug. Samples also were analyzed by use of a nonspecific commercial benzodiazepine fluorescence polarization immunoassay (FPIA). Correlation between the FPLA and HPLC assay was strongest for diazeparn (R2 = 0.84), weak for desmethyldiazepam (R2 = 0.09), and nonexistent for oxazepam. We conclude from a comparison of assays that HPLC is preferred over the FPLA method for measuring benzodiazepines in dogs.

Consumption of chlortetracycline (CTC) at concentration of 220 mg/kg of feed for 4 weeks in experiment 1 and at concentrations of 110 and 220 mg/kg for 3 weeks and 440 mg/kg for 2 weeks in experiment 2 failed to eliminate streptococci-induced lymphadenitis from swine referred to as principals. Abscesses, mostly in the head and neck, developed in at least a third of all swine in the various groups fed these CTC concentrations. Feeding of 220 mg of CTC/kg of feed in experiment 1 began 12 weeks after exposure of principals to an untypeable group E streptococci (GES; isolate 3X29A). In experiment 2, feeding of 110 and 220 mg of CTC/kg of feed began 5 weeks after exposure of principals to GES and feeding of 440 mg of CTC/kg of feed began 6 weeks after exposure. One or more cohabitating sentinel swine of experiment 1 and one or more sentinels in all groups of principals of experiment 2, except group 2, developed abscesses that were mostly in the head and neck. In experiment 2, correlation between serum GES antibody titer and development of one or more abscesses in the principals was highly significant (P < 0.01); however, correlation between antibody titer and abscesses in the sentinels only approached significance (P < 0.10).

Albendazole, administered orally at a dose rate of 25 mg/kg of body weight to presumed pregnant cows or heifers on days 21, 31, 41, 51, and 61 of gestation, did not induce toxicosis in embryos or fetuses, and all calves born were structurally normal. Albendazole administration at a rate of 25 mg/kg to cows at 7 and/or 14 days of gestation decreased the apparent conception rate (ie, embryolethality), but did not have a teratogenic effect. Apparent embryolethality was greater in cows administered 25 mg/ kg only on day 14, compared with those administered the drug only on day 7. Single dosage of 25 mg/kg given in the final 3 months of gestation did not induce abortion. There were no adverse effects of albendazole at a dosage of 10 or 15 mg/kg on developing embryos or fetuses when administered to presumed pregnant cows at various times in early gestation.

Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were surgically thyroidectomized and used in a Latin-square design pharmacokinetic study of orally administered L-thyroxine. The dogs were treated with 44, 22, and 11 Kg of L-thyroxine/kg as a single morning dose or in divided doses, morning and evening. Serum concentration of thyroxine (T4) was evaluated to determine a number of pharmacokinetic variables for comparison. Mean steady-state concentrations (C(SS)) were determined from the area under the curve. Variables were analyzed for comparisons between dosages by use of ANOVA. Concentration at steady state was highest for dogs of the 44-micrograms/kg of body weight once-daily group and was lowest for dogs of the group given 11 micrograms/kg in 2 daily doses. Single daily administration resulted in higher C(SS), except at the 22-micrograms/kg/d dosage. Clearance was faster for the 22- and 44-micrograms/kg/d dosages than for the 11-micrograms/kg/d dosage. The half-life (t(1/2)) and mean residence time (MRT) also were shorter for the 44-micrograms/kg/d dosage, possibly indicating more rapid elimination of the drug at higher doses and dose-dependent kinetics. Perhaps, as the dogs' metabolism increased with higher iodothyronine concentrations, hormone degradation was accelerated. Interval (divided vs single dose) caused some expected changes: maximal concentration was higher and minimal concentration was lower when single administration was used. These undulations resulted in iodothyronine concentrations above the physiologic range for a number of hours, whereas concentration closer to physiologic ranges was achieved by use of divided doses. Delayed absorption (lag time) was seen in 37 of the 72 data sets, but was generally short, about 0.25 hour. Mean time to maximal concentration was 3 to 4 hours. At the higher dosages, serum total T4 concentration was high normal or above normal during most of the time after L-thyroxine administration, but serum concentration of total 3,5,3'-triiodothyronine did not remain within the normal range until the 44-micrograms/kg/d dosage was used. The customary dosage of 22 micrograms/kg/d (0.1 mg/10 lb/d) may not be adequate for most dogs. Pharmacokinetic variables appear to be highly dependent on the individual dog. Those with rapid absorption and higher concentration tended to have these characteristics at each dosage in this study. The pharmacokinetic variables, therefore, appear to be highly individualized, and dosages recommended for treatment of hypothyroidism should be considered to be only a starting point for the average dog. To avoid underdosing or overdosing, monitoring of treatment to adjust dose for individual dog kinetic variables seems to be imperative.