Ciprofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to 4 healthy dogs at dosage of approximately 11 and 23 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) concentrations of ciprofloxacin were measured after the first and seventh dose of each dosing regimen. The peak concentration was greatest in the serum after multiple doses of 23 mg/kg (mean +/- SEM; 5.68 +/- 0.54 micrograms/ml) and least in the TCF after a single dose of 11 mg/kg (0.43 +/- 0.54 micrograms/ml ml). The time to peak concentration was not influenced by multiple dosing or drug dose, but was longer for TCF (6.41 +/- 0.52 hour) than for serum (1.53 +/- 0.52 hour). Accumulation of ciprofloxacin was reflected by the area under the concentration curve from 0 to 12 hours after administration (AUC 0 leads to 12). The AUC 0 leads to 12 was greatest in the serum after multiple doses of 23 mg/kg (31.95 +/- 1.90 micrograms.h/ml) and least in the TCF after a single dose of 11 mg/kg (3.87 +/- 1.90 micrograms.h/ml). The elimination half-life was not influenced by multiple dosing or dose concentration, but was greater for TCF (14.59 +/- 1.91 hours) than for serum (5.14 +/- 1.91 hours). The percentage of TCF penetration (AUCTCF/AUCserum) was greater after multiple doses (95.76 +/- 6.79%) than after a single dose (55.55 +/- 6.79%) and was not different between doses of 11 and 23 mg/kg. Both dosing regimens of ciprofloxacin resulted in continuous serum and TCF concentrations > 90% of the minimal inhibitory concentration for the aerobic and facultative anaerobic clinical isolates tested, including Pseudomonas aeruginosa.

Pharmacokinetic variables were calculated from time-concentration data obtained after IV (10 mg/kg of body weight; n = 9) and oral (12.5 mg/kg to group A [n = 3]; 25 mg/kg to group B [n = 3]; and 50 mg/kg to group C [n = 3] pigs) cyclosporine (formerly, cyclosporine A) administration. Resulting mean (+/- SD) pharmacokinetic variables were as follows: half life of distribution, 0.96 (+/- 0.7) hours; half life of elimination, 7.71 (+/- 2.6) hours; volume of distribution at steady state, 4.47 (+/- 2.22) L/kg; volume of the central compartment, 1.71 (+/- 0.78) L/kg; and systemic clearance, 8.95 (+/- 2.7) ml/kg/min. Oral bioavailability was: overall 57 (+/- 19) %; group A, 44 (+/- 11) %; group B, 78 (+/- 15) %; group C, 48 (+/- 6) %. Time to peak concentration was 3.55 (+/- 0.88) hours. During the 22 days of daily oral cyclosporine administration, blood 24-hour trough concentrations were: group A, 224.3 (+/- 78.4) ng/ml; group B, 640.7 (+/- 174.6) ng/ml; and group C, 2,344 (+/- 1,095) ng/ml. Lymphoblast transformation stimulation index was suppressed in all pigs except 1, which had a corresponding cyclosporine concentration of 92.4 ng/ml. Minimal, although statistically significant, decreases in serum albumin and magnesium concentrations and increases in serum creatinine and urea nitrogen concentrations were evident in pigs of some treatment groups. Histologic examination of necropsy specimens revealed mild hepatic necrosis (n = 1 pig), renal tubular dilatation (n = 5), and pulmonary inflammation (n = 2). Pigs given 25 and 50 mg of cyclosporine/kg failed to gain weight.

Colostrum-deprived lambs and CF1 mice were vaccinated with water-in-oil emulsion vaccines containing nonviable whole cells (WC) of Corynebacterium pseudotuberculosis with and without muramyl dipeptide (MDP). Efficacy of vaccines was determined from the survival of mice and lesions in lambs after IV injection of 10(4) colony-forming units of C pseudotuberculosis. In mice, protection was related to the concentration of WC in the vaccine. At 50, 100, or 150 micrograms of WC, protection was good (78.8%). At 10 or 25 micrograms of WC, protection was considerably less (54.7%). At high WC concentrations, protection could only be moderately increased to 82.3% with high (50 and 100 micrograms) concentrations of MDP or increased to 90% protection with low (5 and 10 micrograms) concentrations of MDP. At low WC concentrations, protection significantly decreased to 32% (P < 0.025) with high concentrations of MDP, but significantly increased to 72.5% (P < 0.025) with low concentrations of MDP. Therefore, the amount of protection with lower concentrations of WC and MDP was comparable with the amount of protection with higher concentrations of WC without MDP. In lambs, high prechallenge antibody titers (geometric mean titers from 5.1 to 5.4 by day 35) were observed after vaccination with WC. Protection and vaccination site abscesses in lambs were related to the concentration of WC and MDP. Pulmonary or vaccination site abscesses were not observed in 4 of 4 lambs vaccinated with 1 mg of WC + 50 micrograms of MDP.

Inhibitory effects of dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP) inhibitory effects on erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (ChE) activities of steers were characterized after treatments in vitro and in vivo (cutaneous application). The rates of in vitro inhibition were markedly influenced by DDVP concentration and incubation time. The activities of inhibited enzymes failed to reactivate spontaneously and had little response to treatment with 2-pyridine aldoxime methiodide (2-PAM). After gel-filtration chromatography, however, the inhibited enzymes had remarkable spontaneous reactivation and reactivation by 2-PAM treatment, indicating interference of excess unreacted DDVP in the reactivation process. Repeated cutaneous applications of a DDVP-containing livestock spray caused marked and characteristic decreases of AChE and ChE activities in blood of treated steers; however, the effects were transient because activities of both enzymes regenerated gradually. The nature of these in vivo trends suggests that spontaneous and de novo synthetic mechanisms could be responsible for complete recovery of both enzyme activities.

The effects of different arterial carbon dioxide tensions (PaCO2) on cerebrospinal fluid pressure (CSFP) and intraocular pressure (IOP) were studied in 6 male halothaneanesthetized horses positioned in left lateral recumbency. Steady-state anesthetic conditions (1.06% end-tidal halothane concentration) commenced 60 minutes following anesthetic induction with only halothane in oxygen. During atracurium neuromuscular blockade, horses were ventilated, and respiratory rate and peak inspiratory airway pressure were maintained within narrow limits. The CSFP and IOP were measured at 3 different levels of PaCO2 (approx 40, 60, and 80 mm of Hg). The PaCO2 sequence in each horse was determined from a type of switchback design with the initial PaCO2 (period 1), established 30 minutes after the commencement of steady-state anesthesia, being repeated in the middle (period 3) and again at the end (period 5) of the experiment. Measurements taken from the middle 3 periods (2, 3, and 4) would form a Latin square design replicated twice. The interval between each period was approximately 45 minutes. Data from periods 2, 3, and 4 indicated that CSFP (P < 0.05) and mean systemic arterial pressure increased significantly (P < 0.05) with high PaCO2. Mean central venous pressure, heart rate, and IOP did not change significantly during these same conditions. Measurements taken during periods 1, 3, and 5 were compared to assess the time-related responses to anesthesia and showed a significant increase in CSFP, a significant decrease in mean central venous pressure, and a small (but not statistically significant) increase in mean systemic arterial pressure.

Colony hybridizations with DNA probes for 3 heat-stable (STaP, STaH, and STb) enterotoxins and 1 heat-labile (LT) enterotoxin and for 4 adhesins (K99, F41, K88, 987P) were performed on 870 Escherichia coli isolates to determine pathotypes prevalent among enterotoxigenic E coli (ETEC) isolated from cattle in Belgium. One hundred thirty-two E coli isolates (15.2%) hybridized with probes STaP, K99, and/or F41. The 5 other probes were not hybridized by E coli isolates. Therefore, only STaP enterotoxin and K99 and F41 adhesins were virulence factors of ETEC isolated from cattle. Two major pathotypes accounted for 95% of the ETEC: STaP+K99+F41+ (67.4%) and STaP+K99+ (27.3%). The last 5% of probe-positive isolates had STaP+, STaP+F41+, or K99+F41+ minor pathotypes. Of 12 American ETEC isolates also assayed, 7 were positive with STb and/or 987P probes (pathotypes STaP+STb+,STaP+ 987P+, or STaP+STb+987P+) and may be porcine- rather than bovine-specific enteropathogens. The remaining 5 American ETEC isolates belonged to 3 minor pathotypes (STaP+,STaP+F41+, and K99+F41+) also found among Belgian E coli isolates. Such isolates may be derivatives of STaP+K99+F41+ or STaP+K99+ ETEC after in vivo or in vitro loss of virulence genes and/or non-ETEC isolates, which have acquired virulence genes by in vivo transfer.

Spleen cells from a calf immunized with bovine herpesvirus-1 (BHV-1) were fused with the nonsecreting murine cell line SP2/0. Several bovine-murine hybridomas secreting bovine immunoglobulins were stabilized. Of these, 9 hybridomas secreted bovine monoclonal antibodies that specifically bound to BHV-1 in a radioimmunoassay. Two of these monoclonal antibodies reacted specifically with BHV-1 in an indirect fluorescent antibody test and immunoprecipitated a BHV-1 glycoprotein with molecular mass of 97 kilodaltons.

A functional assay for equine plasminogen was established, using urokinase as the activator, a synthetic chromogenic substrate, a computer-assisted centrifugal analyzer, and acidified/neutralized plasma. One documented effect of plasma acidification appears to be inactivation of alpha-2-antiplasmin. Intra- and interassay precision testing yielded coefficients of variation of 4.1% (n = 10) and 5.6% (n = 26), respectively. Plasminogen was stable in equine plasma stored up to 1 week at 4 C and up to 5 months at -70 C. Plasminogen in nonacidified equine plasma was not activated by urokinase, streptokinase, tissue plasminogen activator, or tissue plasminogen activator plus soluble fibrin. Streptokinase also failed to activate plasminogen in acidified/neutralized equine plasma.

Muscle damage attributable to selenium (Se)/vitamin E deficiencies is known to develop at birth or later in lambs. The purpose of this study was to determine whether and when muscle damage develops in utero. Thirty pregnant ewes maintained on Se-deficient forages from birth were allotted to 3 equal groups. Half of each group was given a single IM injection of 0.056 mg of Se/kg of body weight, 1 month before parturition. At 3 weeks before parturition, cesarean section-derived fetuses from Se-deficient ewes did not have evidence of muscle damage. At 2 weeks before parturition, fetuses from Se-deficient ewes had biochemical evidence of congenital nutritional myopathy, as evidenced by low blood Se concentration (P < 0.05) and by increased plasma creatine kinase (P < 0.001) and lactate dehydrogenase (P < 0.01) activities, compared with fetuses from Se-treated ewes. Thus, for optimal protection of fetuses and newborn lambs in Se-deficient areas, Se should be administered to ewes at least 1 month before parturition.

Effects of dietary aflatoxin (AF) and T-2 toxin, singly and in combination, were evaluated in growing crossbred (Yorkshire X Landrace X Hampshire) pigs. The experimental design consisted of 4 treatment groups of 6 barrows each fed diets containing 0 mg of AF and T-2/kg of feed (controls; group 1), 2.5 mg of AF/kg of feed (group 2), 10 mg of T-2/kg of feed (group 3), or 2.5 mg of AF plus 10 mg of T-2/kg of feed (AF + T-2; group 4) ad libitum for 28 days (7 to 11 weeks of age). Production performance, and serum biochemical, and hematologic evaluations were made weekly. Body weight and body weight gain were depressed by all toxin treatments, but the effect of AF and T-2 toxin in combination was less than additive. Liver and kidney weights, as a percentage of body weight, were increased by AF treatment, and heart weight, as a percentage of body weight, was increased by T-2 treatment. Treatment with T-2 toxin induced necrotizing contact dermatitis on the snout, buccal commissures, and prepuce. Consumption of AF resulted in increased serum activities of alkaline phosphatase, aspartate transaminase, cholinesterase, and gamma-glutamyltransferase, and decreased serum concentrations of urea nitrogen, cholesterol, albumin, total protein, calcium, potassium, magnesium, and phosphorus. Consumption of T-2 toxin resulted in increased serum triglyceride concentration and decreased serum iron concentration. Treatment with AF induced lower serum unsaturated iron-binding capacity and high RBC count, PCV, hemoglobin concentration, WBC count, and prothrombin time. Treatment with T-2 toxin induced microcytic hypochromic anemia, increased numbers of circulating metarubricytes and decreased absolute numbers of lymphocytes. Hepatocellular lesions in barrows of the AF and the AF plus T-2 groups (2 and 4, respectively) were compatible with aflatoxicosis. When fed in combination, each toxin appeared to have a sparing action on certain effects of the other, and the responses elicited were either additive or less than additive.