A study was conducted to determine aflatoxins in tissues and non-tissues of 2 Holstein cows given oral doses of 0.35 mg of purified aflatoxin B1/kg of body weight/day for 3 consecutive days. Cow 1 was slaughtered 24 hours after the 3rd dose, and cow 2, after day 3, was fed aflatoxin-free rations for 7 additional days before slaughter. Tissue samples of brain, gallbladder and bile, heart, intestine, kidney, liver, lung, mammary gland, skeletal muscle, spleen, supramammary lymph nodes, thymus, and tongue, and nontissue samples of blood, feces, milk, rumen content, and urine were examined. Aflatoxins B1 and M1 were found in all samples of cow 1, except the thymus. Kidney, liver, and mammary gland had the highest concentrations of total aflatoxins (57.9, 13.2, and 25.1 ng/g, respectively), with the aflatoxin M1 concentration 40 times more than the aflatoxin B1 level in kidney. Aflatoxin residues were present (0.02 to 0.11 ng/g) only in kidney, liver, and intestine of the tissues from cow 2 (fed aflatoxin-free feed for 7 additional days). Aflatoxin B1 was not present in nontissue samples, but aflatoxin M1 (0.10 and 1.5 ng/ml) was found in the last milk and urine samples from the same cow. Urine assays are a possible way to monitor the presence of aflatoxin residues in meat tissues.

Tall fescue (Festuca arundinacea Shreb) hay from a source known to cause "fescue foot" in grazing cattle was extracted with 80% ethanol. The ethanolic extract was further refined and fractionated into cation,nion, and neutral f fractions by ion-exchange chromatography. The cation fraction was partitioned with alkaline-chloroform to give chloroform-extractable cation and residual cation fractions. All fractions plus the crude ethanolic extract were assayed for toxic activity by intraperitoneal injection into 12 calves (weighting 152.4 to 241.3 kg each) over a 14-day period. Clinical signs of fescue foot were observed on the 5th day in calves given the anion and crude ethanolic extracts. Lameness, swelling, and reddening of the rear coronary bands, discoloration of the tip of the tail, and other signs of fescue foot were seen. Microscopically, coronary bands and tail tips of affected calves had blood vessels with thick walls and small lumens.

Objective--To determine the contribution of 7,8-methylenedioxylycoctonine (MDL)–type alkaloids to the toxic effects of tall larkspur (Delphinium spp) consumption in cattle. Animals--Sixteen 2-year-old Angus steers. Procedures--Plant material from 3 populations of tall larkspur that contained different concentration ratios of MDL-type-to-N-(methylsuccinimido) anthranoyllycoctonine (MSAL)–type alkaloids was collected, dried, and finely ground. For each plant population, a dose of ground plant material that would elicit similar clinical signs of toxicosis in cattle after oral administration was determined on the basis of the plants' MSAL-type alkaloid concentration. Cattle were treated via oral gavage with single doses of ground plant material from each of the 3 populations of tall larkspur; each animal underwent 1 to 3 single-dose treatments (> = 21-day interval between treatments). Heart rate was recorded immediately before (baseline) and 24 hours after each larkspur treatment. Results--Tall larkspur populations with a lower MDL-type-to-MSAL-type alkaloid concentration ratio required a greater amount of MSAL-type alkaloids to cause the expected clinical signs of toxicosis (including increased heart rate) in cattle. Conclusions and Clinical Relevance--Results indicated that the typically less toxic MDL-type alkaloids contributed in a significant manner to the toxic effects of tall larkspur in steers. Consequently, both the concentration of MSAL-type alkaloids and the total concentration of MSAL- and MDL-type alkaloids should be determined when assessing the relative toxicity of tall larkspur populations. These results provide valuable information to determine the risk of toxicosis in cattle grazing on tall larkspur–infested rangelands.

Objective-To inoculate white-tailed deer (Odocoileus virginianus) during the sixth or seventh week of gestation with bovine viral diarrhea virus (BVDV) and observe for signs of reproductive tract disease during a 182-day period. Animals-10 pregnant white-tailed deer (8 seronegative and 2 seropositive [control deer] for BVDV). Procedures-Deer were inoculated with 1 of 2 deer-derived BVDV strains (RO3-20663 or RO3-24272). Serum anti-BVDV antibody titers were determined prior to and 21 or 35 days after inoculation. Virus isolation (VI) procedures were performed on tissues from fetuses and does that died and on blood samples collected from live fawns. Ear notch specimens obtained from live fawns were assessed by use of BVDV antigen-capture ELISA (ACE). Results-Both RO3-20663-inoculated seropositive deer gave birth to apparently normal fawns. Among the RO3-24272-inoculated seronegative deer, 1 died, and 1 aborted and 1 resorbed their fetuses; among the RO3-20663-inoculated seronegative deer, 3 died, 1 aborted its fetus, and 1 gave birth to 2 fawns that were likely persistently infected. On the basis of VI and ACE results, those 2 fawns were positive for BVDV; both had no detectable neutralizing anti-BVDV antibodies in serum. Conclusions and Clinical Relevance-Reproductive tract disease that developed in pregnant white-tailed deer following BVDV inoculation was similar to that which develops in BVDV-exposed cattle. Methods developed for BVDV detection in cattle (VI, immunohistochemical evaluations, and ACE) can be applied in assessments of white-tailed deer. Fawns from does that had serum anti-BVDV antibodies prior to inoculation were protected against BVDV infection in utero.

Calves persistently infected (PI) with Bovine viral diarrhea virus (BVDV) represent an important source of infection for susceptible cattle. We evaluated vaccine efficacy using calves PI with noncytopathic BVDV2a for the challenge and compared tests to detect BVDV in acutely or transiently infected calves versus PI calves. Vaccination with 2 doses of modified live virus vaccine containing BVDV1a and BVDV2a protected the calves exposed to the PI calves: neither viremia nor nasal shedding occurred. An immunohistochemistry test on formalin-fixed ear notches and an antigen-capture enzyme-linked immunosorbent assay on fresh notches in phosphate-buffered saline did not detect BVDV antigen in any of the acutely or transiently infected calves, whereas both tests had positive results in all the PI calves.

Objective-To determine whether inflammation of the jejunum of horses decreases the number of motilin receptors and amounts of motilin receptor mRNA and alters erythromycin lactobionate binding affinity to the motilin receptor in jejunal tissues. Sample Population-Jejunal segments in 6 adult horses. Procedure-Each horse was anesthetized, and a ventral median celiotomy was performed; 2 segments of jejunum underwent a sham operation, 2 segments underwent ischemic strangulation obstruction (ISO), and 2 segments underwent intraluminal distension (ILD). Treatments were maintained for 120 minutes. From each segment, full-thickness biopsy samples were collected and smooth-muscle homogenates were prepared. Affinity and distribution of motilin binding to these preparations were determined by use of iodine 125 (125I)-labeled synthetic porcine motilin. Via displacement experiments, competition between 125I-labeled motilin and erythromycin lactobionate for binding to motilin receptors in the different segments was investigated. A quantitative real-time PCR technique was used to assess motilin receptor mRNA content in the muscle preparations. Results-Compared with the ISO or ILD segments, the number of motilin receptors was significantly higher in the sham-operated segments; ILD segments contained the lowest number of motilin receptors. The expression of motilin receptor mRNA was significantly decreased in ILD segments but not in ISO segments. Erythromycin lactobionate displacement of 125I-labeled motilin from motilin receptors did not differ significantly among the jejunal segments. Conclusions and Clinical Relevance-Results suggest that downregulation and decreased production of motilin receptors in inflamed jejunal tissue contribute to the altered prokinetic response to erythromycin in horses with gastrointestinal disease.

Objective-To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. Animals-6 healthy mature horses. Procedures-A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. Results-Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (C(max)) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and C(max) was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. Conclusions and Clinical Relevance-Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.

Objective-To evaluate the effects of subarachnoidally administered hyperbaric morphine, buprenorphine, and methadone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses. Animals-6 healthy adult horses. Procedures-Horses were assigned to receive subarachnoid administration of hyperbaric morphine (0.01 mg/kg), buprenorphine (0.001 mg/kg), methadone (0.01mg/kg), or 10% dextrose solution in equal volumes (5 mL). Electrical stimulation was applied every 10 minutes for 60 minutes and every 30 minutes for 120 minutes after subarachnoid injection over the dermatomes of the perineal, sacral, lumbar, and thoracic regions, and the avoidance threshold voltage was recorded. Heart and respiratory rate, blood gas tensions, serum electrolyte concentrations, and sedative effects were also evaluated. Results-Administration of 10% dextrose solution did not change the avoidance threshold. Morphine and methadone significantly increased the avoidance threshold by 10 minutes after injection, which lasted until 120 minutes after subarachnoid administration in the perineal, sacral, lumbar, and thoracic regions. Profound analgesia (avoidance threshold > 40 V) was achieved in all regions. Buprenorphine also significantly increased the avoidance threshold by 10 minutes (36 V) after injection, which lasted 60 minutes and was considered moderate. Heart rate, blood pressure, respiratory rate, and blood gas tensions stayed within reference range. No ataxia, signs of sedation, or CNS excitement were observed. Conclusions and Clinical Relevance-Subarachnoid administration of hyperbaric morphine or methadone produces intense analgesia for 120 minutes over the dermatomes of the perineal, sacral, lumbar, and thoracic areas without cardiorespiratory depression, ataxia, or CNS excitement in horses.

Objective-To determine the pharmacokinetic disposition of IV administered caffeine in healthy Lama spp camelids. Animals-4 adult male alpacas and 4 adult female llamas. Procedures-Caffeine (3 mg/kg) was administered as an IV bolus. Plasma caffeine concentrations were determined by use of high-performance liquid chromatography in 6 animals and by use of liquid chromatography-mass spectrometry in 2 llamas. Results-Median elimination half-life was 11 hours (range, 9.3 to 29.8 hours) in alpacas and 16 hours (range, 5.4 to 17 hours) in llamas. The volume of distribution at steady state was 0.60 L/kg (range, 0.45 to 0.93 L/kg) in alpacas and 0.75 L/kg (range, 0.68 to 1.15 L/kg) in llamas. Total plasma clearance was 44 mL/h/kg (range, 24 to 56 mL/h/kg) in alpacas and 42 mL/h/kg (range, 30 to 109 mL/h/kg) in llamas. Conclusions and Clinical Relevance-High-performance liquid chromatography and liquid chromatography-mass spectrometry were suitable methods for determination of plasma caffeine concentrations in alpacas and llamas. Plasma caffeine concentration-time curves were best described by a 2-compartment model. Elimination half-lives, plasma clearance, volume of distribution at steady state, and mean residence time were not significantly different between alpacas and llamas. Intravenous administration of caffeine at a dose of 3 mg/kg did not induce clinical signs of excitement.

Objective-To compare serum concentrations of liposome-encapsulated butorphanol tartrate (LEBT) and standard butorphanol tartrate (STDBT) following SC and IM administration, respectively, and to evaluate analgesic effects of LEBT and STDBT after parenteral administration to Hispaniolan parrots. Animals-11 adult Hispaniolan parrots. Procedure-The ability of LEBT to prolong the duration of analgesia in an avian species was tested. Blood samples were collected at serial time points after SC administration of LEBT (10 mg/kg or 15 mg/kg) or IM administration of STDBT (5 mg/kg). Serum concentrations of butorphanol tartrate were determined by use of a commercial immunoassay that measured parent drug and metabolites. Analgesic efficacy was evaluated in parrots exposed to electrical and thermal stimuli. Foot withdrawal thresholds were recorded at baseline and at serial time points after LEBT (15 mg/kg), liposome vehicle, STDBT (2 mg/kg), or physiologic saline (0.9% NaCl) solution administration. Results-LEBT had a prolonged in vivo release for up to 5 days. Negligible serum butorphanol and butorphanol metabolite concentrations were obtained at 24 hours after IM administration of STDBT. Analgesic efficacy of LEBT as measured by foot withdrawal threshold to noxious thermal and electrical stimuli persisted for 3 to 5 days following SC administration of LEBT. Conclusions and Clinical Relevance-SC administration of LEBT provided analgesia and detectable serum butorphanol concentrations in Hispaniolan parrots for up to 5 days. The use of LEBT may allow for substantial improvement in long-term pain relief without subjecting birds to the stress of handling and multiple daily injections.