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.

The objective of this study was to evaluate the endocrine and immune responses of steers challenged with infectious bovine rhinotracheitis virus (IBRV). For the study, twelve crossbred beef steers weighing approximately 228.82 kg were fitted with indwelling rectal temperature monitoring devices and randomly assigned to a Control (CON) or IBRV treatments. Immune challenged steers received an intra-nasal dose of IBRV (4 ml total volume; 2ml/nostril) and CON steers received an intra-nasal dose of saline (2 ml/nostril). On day 0, steers were challenged and placed into isolated paddocks. At 72 hours post-inoculation, steers were fitted with indwelling jugular catheters and placed into individual stanchions. Blood samples were intensively collected on days 4 through 8 post-inoculation. Serum was analyzed for cortisol, interleukin-6, interferon-gamma, tumor necrosis factor-alpha, growth hormone, and insulin-like growth factor-1. On day 2, IBRV challenged steers had increased rectal temperature compared to CON steers (P < 0.05); the greatest rectal temperatures were observed on day 4, after which rectal temperatures returned to baseline by day 6. Serum concentrations of cortisol, interferon-gamma, and growth hormone exhibited a similar response pattern increasing by day 2 for the IBRV challenged steers, with the greatest increases observed on day 4, and subsiding on day 6. There was a decrease (P = 0.04) in growth hormone production in IBRV challenged steers, but no difference in insulin-like growth factor-1. Collectively, the data revealed that alterations in the somatotrophic axis were not associated with large increases in circulating pro-inflammatory cytokines. Results suggest that the dose of the virus used in the present study, while sufficient to elicit a febrile response, was not enough to elicit a robust pro-inflammatory immune response.

Objective-To assess the biological response to recombinant feline interferon-omega (rFeIFN-omega) following ocular or oral administration in cats via estimation of Mx protein expression in conjunctival cells (CCs) and WBCs. Animals-10 specific pathogen-free cats. Procedures-In multiple single-dose drug experiments, each cat received various concentrations of rFeIFN-omega administered topically into both eyes (50 to 10,000 U/eye) and orally (200 to 20,000 units). The same cats received saline (0.9% NaCl) solution topically and orally as control treatments. The CCs and WBCs were collected prior to treatment (day 0), on day 1, and every third or seventh day thereafter until samples yielded negative results for Mx protein. Samples were examined for Mx protein expression via immunohistochemistry and immunoblotting procedures involving murine anti-Mx protein monoclonal antibody M143. Results-After topical application of 10,000 U of rFeIFN-omega/eye, CCs stained for Mx protein for a minimum of 7 days, whereas WBCs were positive for Mx protein for a minimum of 31 days. After topical application of lower concentrations, CCs did not express Mx protein, in contrast to WBCs, which stained for Mx protein at 1,000 units for at least 1 day. Following oral administration, Mx protein was expressed in WBCs at rFeIFN-omega concentrations as low as 200 units, whereas CCs did not stain for Mx protein at any concentration. Conclusions and Clinical Relevance-Results indicate that Mx protein expression (a marker of the biological response to rFeIFN-omega) in CCs and WBCs of rFeIFN-omega-treated cats depends on the dose of rFeIFN-omega, site of administration, and cell type.

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.

Pharmacodynamic variables of enrofloxacin were investigated in a neutropenic mouse Escherichia coli and staphylococcal thigh infection model. Enrofloxacin pharmacokinetics in clinically normal mice and dogs were compared to confirm that doses evaluated in the mouse model would include enrofloxacin doses appropriate for use in dogs. Mice were made neutropenic by treatment with cyclophosphamide and injected in the thigh muscle with approximately 10(6) colony-forming units of E. coli (n = 2) or a staphylococcal (n = 2) clinical isolate. Enrofloxacin dosages tested ranged from 0.78 to 50 mg/kg of body weight and 6.25 to 200 mg/kg in the E. coli and staphylococcal infection trials, respectively. In each 24-hour dosage trial, enrofloxacin was administered SC as a single dose or in divided doses given every 3, 6, or 12 hours. Comparison of log(10) colony-forming units per thigh muscle in untreated control mice and mice treated with enrofloxacin was used as a measure of efficacy. Two-way ANOVA was used to determine that the enrofloxacin total dose, but not the dose frequency, was significant in determining drug efficacy. Pharmacokinetic values analyzed by use of multivariant stepwise linear regression analysis indicated that the area under the concentration-time curve, but not time above minimum inhibitory concentration, was significant in predicting efficacy of enrofloxacin treatment. We conclude that enrofloxacin killing of E. coli and staphylococci is concentration dependent and not time dependent.

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.

Palmar digital arterial blood flow was measured in 6 conscious, standing horses, using surgically placed perivascular ultrasonic flow probes. The effects of 2 dosages of xylazine (0.55 and 1.1 mg/kg of body weight) and of 3 dosages of acetylpromazine (0.01, 0.02, and 0.04 mg/kg), as well as the effect of vertical load, on digital blood flow were evaluated. Intravenous administration of xylazine induced a significant (P < 0.05), transient decrease in digital blood flow. Intravenous administration of acetylpromazine induced a significant (P < 0.05), prolonged increase in digital blood flow. Correlation between vertical load and digital blood flow was found. The results of this study indicate that use of acetylpromazine may be beneficial in clinical treatment of horses with reduced digital blood flow. Xylazine, on the other hand, may exacerbate ischemic conditions of the digit and should be used with caution.

A bolus dose of methimazole (MMI) was administered IV over 1 minute to 5 healthy adult dogs at a dosage (40 mg/kg of body weight) known to impart protection against cisplatin-induced renal disease. Blood and urine samples for pharmacokinetic analysis were collected over a 24-hour period. Physical examination, CBC, determination of serum thyroid hormone concentrations, and serum biochemistry analysis were performed over a 10-day period to evaluate short-term toxicoses. At this dosage, MMI appears to be safe and well tolerated in dogs; only 1 of the 5 dogs had mild and transient increases in serum activity of hepatic enzymes. In addition, MMI did not alter serum thyroid hormone concentrations. Half-life of 8.82 hours and mean residence time of 12.18 hours were determined for MMI. Renal clearance of native MMI, along with sulfate and glucuronide conjugates, represented only 20% of total systemic clearance. Results of this study provide further information concerning clinical use of MMI in dogs and may contribute to better understanding of the mechanism of MMI protection against chemically induced nephrotoxicosis.

Efficacy of albendazole for treating giardiasis in dogs was assessed in 3 experiments. In experiment 1, Giardia cysts were cleared from feces of 5 of 7 dogs (as determined by the zinc-sulfate concentration technique) after the dogs received a single dose of albendazole (25 mg/kg of body weight, PO), whereas feces of 3 of 7 dogs became clear of cysts without treatment. In experiment 2, feces of 5 of 5 dogs became clear of cysts after albendazole treatment (25 mg/kg, PO, q 12 h for 4 doses); feces of 1 of 5 untreated control dogs became clear. In experiment 3, feces of 18 of 20 dogs became clear of cysts after albendazole 25 mg/kg, PO, q 12 h for 4 doses) was given; none of the 20 control dogs had feces clear of cysts. Signs of toxicosis were not observed in any dog. These results indicate that a single dose of albendazole (25 mg/kg, PO) is not effective for treating giardiasis in dogs. However, 4 doses of albendazole (25 mg/kg, PO, q 12 h) are highly effective and nontoxic for treatment of giardiasis in dogs.