Twenty-nine healthy 17- to 29-day-old unweaned Isaeli-Friesian male calves were each given a single IV or IM injection of 10 or 20 mg of moxalactam disodium/kg of body weight. Serum concentrations were measured serially during a 12-hour period. Serum concentration vs time profiles were analyzed by use of linear least-squares regression analysis and the statistical moment theory. The elimination half-lives after IV administration were 143.7 +/- 30.2 minutes and 155.5 +/- 10.5 minutes (harmonic mean +/ SD) at dosages of 10 and 20 mg of moxalactam/kg of body weight, respectively. Corresponding mean residence time values were 153.1 +/- 26.8 minutes and 169.9 +/- 19.3 minutes (arithmetic mean +/- SD). Mean residence time values after IM administration were 200.4 +/- 17.5 minutes and 198.4 +/- 19.9 minutes at dosages of 10 and 20 mg/kg, respectively. The volumes of distribution at steady state were 0.285 +/- 0.073 L/kg and 0.313 +/- 0.020 L/kg and total body clearance values were 1.96 +/- 0.69 ml/min/kg and 1.86 +/- 0.18 ml/min/kg after administration of dosages of 10 and 20 mg/kg, respectively. Moxalactam was rapidly absorbed from the IM injection site and peak serum concentrations occurred at 1 hour. The estimated bioavailability ranged from 69.8 to 79.1%. The amount of serum protein binding was 53.4, 55.0, and 61.5% when a concentration of moxalactam was at 50, 10, and 2 micrograms/ml respectively. The minimal inhibitory concentrations of moxalactam ranged from 0.01 to 0.2 micrograms/ml against Salmonella and Escherichia coli strains and from 0.005 to 6.25 micrograms/ml against Pasteurella multocida strains.

The role of turkey complement in a serum bactericidal reaction was determined using serum-sensitive and serum resistant Escherichia coli isolated from turkeys. Inactivation of complement by heating serum (56 C for 40 minutes) or by treating serum with 10mM EDTA eliminated bactericidal activity. Serum sensitive E coli organisms were killed by turkey serum treated with 10 mM ethylene glycol-bis-beta-(aminoethyl ether)-N, N, N,' N,'-tetraacetic acid and 5 mM MgCl2. Exposure of normal turkey serum to serum-sensitive or serum resistant E coli resulted in equivalent reductions in hemolytic activity of serum. Treatment of serum-resistant E coli with antibody rendered the bacteria sensitive to bactericidal effects of normal turkey serum. Serum-sensitive E coli organisms were readily killed by an alternative complement pathway, serum-sensitive and serum-resistant E coli activated the complement system equally well, and antibody was required for complement-mediated killing of certain serum-resistant E coli organisms from turkeys.

The relationship of serum complement activity and bacteriostatic activity was investigated in male guinea pigs given aflatoxin and/or rubratoxin. In experiment 1, guinea pigs were given 0.6 mg of aflatoxin/kg of body weight, PO, once. In experiment 2, guinea pigs were given 0.02 mg of aflatoxin/kg, PO, and/or 8 mg of rubratoxin, PO, 11 times. Aflatoxin (0.02 mg/kg) had no effect given alone, but potentiated the effect of rubratoxin. In both experiments, changes in complement activity were accompanied by similar but not always significant (P less than 0.05) changes in bacteriostatic activity of serum. Guinea pigs given 0.06 mg of aflatoxin/kg had significant (P less than 0.05) changes in complement titers and in serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase activities. Guinea pigs given repeated oral doses of aflatoxin and/or rubratoxin had changes in complement titers, bacteriostasis, and alkaline phosphatase and aspartate aminotransferase activities, but not in alanine aminotransferase activities. Significant differences were detected only when average values for all guinea pigs given rubratoxin or rubratoxin with aflatoxin were compared with average values for guinea pigs not given rubratoxin.

Phagocytic and oxidative metabolic activities of bovine blood neutrophils were determined in the presence of glycolytic (NaF) and cytoskeletal (colchicine, cytochalasin B, and prostaglandin E1) inhibitors. Phagocytosis and postphagocytic oxidative metabolic activity, measured by nitroblue tetrazolium reduction, were determined using zymosan, Escherichia coli, Staphylococcus aureus, or Streptococcus agalactiae. Sodium fluoride (1.25 micromolar to 1.25 mM concentrations) did not significantly (P greater than 0.05) inhibit phagocytosis of S aureus and Str agalactiae, whereas phagocytosis of zymosan and E coli was significantly (P less than 0.05) inhibited only at 1.25 mM concentration. Colchicine at 1.25 nM to 1.25 micromolar conce ntrations significantly inhibited phagocytosis of zymosan and E coli, but not of S aureus and Str agalactiae. Cytochalasin B at 1.25 nM to 1.25 micromolar concentrations significantly inhibited phagocytosis of zymosan and all 3 bacteria, whereas prostaglandin E1 was noninhibitory at similar concentrations. Nitroblue tetrazolium reduction, in general, was not significantly affected by NaF and cytoskeletal inhibitors.

Serum immunoglobulins of the IgG isotype recognizing common gram-negative cell core epitopes were serially measured, using a direct ELISA, on samples obtained from 20 neonatal Holstein calves. An R-mutant Escherichia coli (strain J5) was used as a plate antigen in this assay. Total serum IgG concentration was measured using radial immunodiffusion. Half-lives of core antigen-specific IgG (7.56 days) and total serum IgG (22.66 days) were dramatically different (P less than 0.0005). This may be an indication of cross-reactive consumption of core antigen-specific immunoglobulins.

Ceftazidime pharmacokinetic values were studied in unweaned calves given the antibiotic alone or in combination with probenecid. Ceftazidime was administered IV to 9 calves at a dosage of 10 mg/kg of body weight and IM (10 mg/kg) to 8 calves, to 7 calves (10 mg/kg plus probenecid [40 mg/kg]), and to 9 calves (10 mg/kg plus probenecid [80 mg/kg]). Serum concentration-vs-time data were analyzed, using noncompartmental methods based on statistical moment theory. The data for IV ceftazidime administration also were fitted by use of a linear, open 2-compartment model. The mean (+/- SD) terminal half-life was 138.7 +/- 23.6 minutes and 126.3 +/- 10.5 minutes after IV and IM administrations, respectively. The mean residence time was 167.3 +/- 21.1 minutes and 201.4 +/- 16.8 minutes after IV and IM administrations, respectively. Coadministration of probenecid did not affect the terminal half-life or mean residence time values. The total body clearance was 1.75 +/- 0.26 ml/min/kg, and the volume of distribution at steady state was 0.294 +/- 0.064 L/kg. The estimated mean absorption time was 34.1 minutes. There were no significant differences between the mean residence time calculated by statistical moment theory or by compartmental analysis, indicating central compartment output of ceftazidime. The 90% minimal inhibitory concentration values of ceftazidime determined for Escherichia coli, Salmonella spp, Pasteurella multocida, and P haemolytica isolates ranged from less than 0.01 to 0.1 microgram/microliter.

A study was conducted to test the hypothesis that high cortisol concentrations associated with products of infections (endotoxin) cause derangement in the neuroendocrine mechanism controlling ovulation in heifers. Eight Holstein heifers were given 2 injections of prostagladin (PG), 11 days apart, to synchronize estrus. Starting from 25 hours after the second injection of PG (PG-2), the uterus of each heifer was infused with 5 ml of pyrogen-free water (control, n =3) or Escherichia coli endotoxin (5 microgram/kg of body weight) in 5 ml of pyrogen-free water (treated, n = 5), once every 6 hours for 10 treatments. Blood samples were obtained every 15 minutes via indwelling jugular catheter for an hour before and 2 hour after each infusion, then hourly until an hour before the next infusion. Ultrasonography of the ovaries was performed every 12 hours, starting 24 hours after PG-2 injection until 96 hours after PG-2 injection. Serum concentrations of luteinizing hormone and cortisol were determined by validated radioimmunoassays. Changes in cortisol concentrations were not detected in control heifers with preovulatory luteinizing hormone surges at 60 to 66 hours after PG-2 injection, followed by ovulations 72 to 96 hours after PG-2 was injected. None of the treated heifers ovulated, and the resulting follicular cysts (14 to 18 mm diameter) persisted for 7 to 21 days. In all treated heifers, serum cortisol concentrations increased (4- to 10-fold) during the first 2 hours after each infusion and then decreased gradually until the next infusion. Luteinizing hormone concentrations remained at baseline values throughout the treatment period in all treated heifers. These findings suggested that endotoxin-induced increases in cortisol concentrations during the preovulatory period of the estrous cycle prevented ovulations by blunting the preovulatory luteinzing hormone surges.

The restriction endonuclease digestion DNA patterns from Brucella abortus strains 19 and 2308 were examined with 11 restriction enzymes (AvaI, BamHI, BglII, BstEII, DdeI, EcoRI, HindIII, KpnI, PstI, XbaI, and SalI)). The DNA electrophoretic banding patterns between the strains were highly similar, using this restriction enzyme analysis. Differences were not discernable between B abortus strains 19 and 2308 in any of the restriction banding patterns examined. Methylation at CCGG or GATC sites was not detectable on the basis of digestion with isoschizomers (HpaII and MspI, and DpnI, Sau3AI and MboI). Homology between B abortus strains 19 and 2308 was assessed, using solution-hybridization techniques followed by S1 nuclease assays. Results of these reassociation experiments indicated 98.6 to 99.3% homology between B abortus strains 19 and 2308 with 13.5 to 18.6% homology between B abortus (strains 19 and 2308) and the E coli HB101 control. We concluded that any DNA differences between the 2 B abortus strains are small and will require analysis at the DNA sequence level.

Live Pasteurella haemolytica biotype A, serotype 1 isolates (n = 3) and Escherichia coli K-12, strain W3110, were reacted with bovine pulmonary lavage cell (PLC) suspensions. The comparative effects of the different bacteria on the functional and metabolic activity of alveolar macrophages (AMO) in the PLC suspensions were assessed simultaneously by use of 51Cr release, luminol-dependent chemiluminescence (LDCL), and AMO bactericidal assays. The bovine PLC reponsed differently to E coli, than to the 3 P haemolytica isolates in each of the 3 experimental test systems; however, responses to each of the P haemolytica isolates were not found to be significantly different. Unopsonized live P haemolytica cells adversely affected the functional and metabolic response of PLC, whereas there was no evidence of a cytotoxic (cytocidal) influence of E coli. A difference in 51Cr release for reaction mixtures containing E coli and P haemolytica was not detected at zero time; however, at each subsequent time, reaction mixtures phagocytically stimulated with P haemolytica had significantly increased amount of 51Cr release (P less than 0.05), compared with those mixtures containing E coli. Bovine AMO in the PLC suspensions were able to effectively kill E coli in vitro, but were unable to prevent survival and subsequent growth of P haemolytica. The luminol-dependent chemiluminescence profiles for reaction mixtures phagocytically stimulated with E coli provided evidence of sustained production of oxygen radicals with antimicrobial capabilities by bovine AMO in the PLC. Production of these highly reactive antimicrobial oxidants appeared initially in cultures containing P haemolytica but, subsequently, their production declined precipitously and ceased altogether.

Ten Holstein heifers were fed a selenium-deficient (SeD) diet (0.04 mg of Se/kg on a total ration dry-matter basis) 3 months before calving and throughout their first lactation. A selenium-supplemented (SeS) diet (2 mg of Se/head/d) was fed to a group of 10 heifers. In about the 14th week of lactation, the cows were challenge-exposed to Escherichia coli by administering 15 to 40 colony-forming units (CFU) into 1 mammary gland. Selenium concentration microgram/ml) in blood around the time of challenge exposure was 0.033 +/-0.002 (mean +/- SEM) in SeD and 0.132 /-0.006 in SeS cows. Infections were established in all challenge-exposed quarters. The frequency of quarter atrophy and agalactia, and reduction in whole-udder milk yield in the first 4 days after challenge exposure, were greater (P < 0.05) in the SeD cows. Log10 peak bacterial concentrations in milk were higher (P < 0.05) in SeD (7.63 +/- 0.34 CFU/ml) than in SeS cows (5.57 0.66 CFU/ml). Mean log bacterial concentration was significantly higher (P < 0.05) from 12 to 20 hours after challenge exposure in SeD than in SeS cows. Duration of infection was significantly greater (P < 0.05) in SeD (162.0 +/- 12.0) than in SeS cows (114.4 +/- 18.0 hours). Milk somatic cell counts increased significantly more slowly (P < 0.05) in SeD than in SeS cows from 8 to 16 hours after challenge exposure. Ratios of milk somatic cells to bacteria in milk were significantly lower (P < 0.05) in SeD than in SeS cows at l2 and 16 hours after challenge exposure.