The role of prostaglandin F2 alpha (PGF2 alpha) in embryonic loss following induced endotoxemia was studied in mares that were 21 to 44 days pregnant. Thirteen pregnant mares were treated with a nonsteroidal anti-inflammatory drug, flunixin meglumine, to inhibit the synthesis of PGF2 alpha caused by Salmonella typhimurium endotoxin given IV. Flunixin meglumine was administered either before injection of the endotoxin (group 1, -10 min; n = 7), or after endotoxin injection into the mares (group 2, 1 hour, n = 3; group 3, 2 hours, n = 3); 12 pregnant mares (group 4) were given only S typhimurium endotoxin. In group 4, the secretion of PGF2 alpha, as determined by plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations, was biphasic, initially peaking at 30 minutes followed by a second, larger peak approximately 105 minutes after the endotoxin was given IV. When flunixin meglumine was administered at -10 minutes, synthesis of PGF2 alpha was inhibited for several hours, after administration of flunixin meglumine at 1 hour, the second secretory surge of PGF2 alpha was blocked, and administration of the drug at 2 hours did not substantially modify the secretion of PGF2 alpha. Plasma progesterone concentrations were unchanged after endotoxin injections were given in group 1. In group 2, progesterone values decreased < 2 ng/ml and remained low for several days. In group 3 and group 4, progesterone concentrations decreased to values < 0.5 ng/ml by 48 hours after endotoxin injections were given. Pregnancy continued in all 7 mares in group 1; in group 2, pregnancy continued in 2 of 3 mares; and in group 3, none of the 3 mares was pregnant by 4 days after endotoxin administration. The abortifacient effect of endotoxemia in mares < 2 months pregnant is mediated indirectly through the secretion of PGF2 alpha; compromised luteal activity and inadequate progesterone secretion are the primary causes of fetal death. Although flunixin meglumine administration can be used to prevent loss of pregnancy in cases of endotoxemia, it must be initiated at an early stage of the endotoxemia, that is, when clinical signs are often not yet apparent.

The antebrachiocarpal and tarsocrural joints of 10 adult horses were randomly assigned to 1 of 4 groups. Groups were formulated and were treated as follows: group 1, control (arthrocentesis only); group 2, buffered lactated Ringer solution; group 3, 10% dimethyl sulfoxide (DMSO; w/v) in lactated Ringer solution; and group 4, 30% DMSO (w/v) in lactated Ringer solution. Joints were lavaged once with the respective solution. Prior to lavage and on days 1, 4, and 8 after lavage, all horses were evaluated for lameness and joint effusion; synovial fluid total and differential WBC counts, synovial fluid total protein concentration, and mucin clot quality were determined. Horses were euthanatized on day 8, and joints were evaluated grossly, histologically, and histochemically. Significant difference was not observed in effect of lactated Ringer solution, 10% DMSO, and 30% DMSO on any measured variable. At 24 hours after treatment, significant (P < 0.05) difference in synovial fluid WBC numbers and total protein concentration was detected between control and treated joints. Eighty percent of lavaged joints had effusion 24 hours after treatment, compared with 30% of control joints. Gross, histopathologic, or histochemical differences were not detected between treated and control joints. Results of the study indicate that buffered lactated Ringer, 10% DMSO, and 30% DMSO solutions induce similar inflammatory changes in articular structures and significantly greater inflammatory reaction than does arthrocentesis alone.

A study was conducted to determine the immune (increased antibody) and protective (reduced colony-forming units) responses induced in mice by a: (i) single vaccinal inoculation, using various concentrations of Brucella cell surface protein (BCSP) or lipopolysaccharide (LPS); (ii) primary inoculation, using various concentrations of BCSP, followed by a secondary inoculation, using a standard concentration of BCSP; and (iii) primary inoculation, using 1 concentration of BCSP or LPS, followed by a secondary inoculation, using various concentrations of BCSP or LPS. Four weeks after the primary inoculation, mice were challenge exposed with approximately 1 X 10(4) colony-forming units of Brucella abortus strain 2308 and all mice were euthanatized at 6 weeks. Reduced splenic weights and reduced colony-forming units in the spleens of vaccinated mice, compared with nonvaccinated mice, were the criteria of protection. Increase in serum IgM and IgG was defined as immunity. Both BCSP and LPS induced protective and immune responses that were proportional to the dose given up to an optimal limit. However, concentrations higher than optimal decreased the protective and immune responses. This was true for mice given either 1 or 2 vaccinal inoculations. Enhanced secondary protective responses were seen only when suboptimal doses were used in the primary inoculation. Excessive or optimal doses in the secondary inoculations prevented or obscured the protectiveness and immunity by primary inoculations. The protective effects appeared to be additive when suboptimal doses were used in the primary and secondary inoculations. Inoculation of subimmunogenic doses induced a relative reduction in the antibody concentration after challenge exposure, compared with nonvaccinated mice. The overall results indicated that the protective responses induced by BCSP were probably attributable to LPS. The results also indicated a linear increase in protection and immune response corresponding to increasing doses up to an optimal dose, and this stoichiometric optimum may be achieved by the use of 1 or more vaccinal inoculations. However, once this optimum was obtained, additional amounts of BCSP or LPS cause perturbation of both the protective and serologic responses.

Canine and human platelets (washed 4 times in a solution containing EDTA, prostaglandin E1, and theophylline to prevent release of alpha-granule constituents) were lysed by being frozen and thawed in the presence of detergent. Radioelectroimmunoassay for von Willebrand factor (vWf) in 5 human platelet lysates produced precipitin rockets, shaped like those produced from vWf in plasma from healthy human beings, and indicated that the mean von Willebrand factor antigen (vWf:Ag) content in platelets from healthy human beings was 526 +/- 87 human U/10(12) platelets. Radioelectroimmunoassay for vWf in platelet lysates from 17 healthy dogs with normal plasma vWf:Ag concentration produced precipitin rockets that looked different from those produced from canine plasma and indicated vWf:Ag content of 59 +/- 35 canine U/10(12) platelets. Inclusion of protease inhibitors in the lysing solution did not normalize the appearance of the precipitin rockets or substantially alter the measured platelet content of vWf:Ag. The array of vWf multimers revealed by sodium dodecyl sulfate-agarose gel electrophoresis of canine platelet lysates had a distinct appearance that differed from that of vwf in canine or human plasma and platelets; the intensity of the canine platelet vWf multimer bands was skewed, with relatively greater density in the lower molecular weight region and faint or undetectable multimer bands in the higher molecular weight region. Electrophoretograms with visible multimers in the high molecular weight region had vwf components that had higher molecular weight than did any vWf components in canine plasma. Radioelectroimmunoassay for fibronectin in these same canine platelet lysates indicated that the fibronectin content in platelets was 2.89 +/- 1.10 mg/10(12) platelets. An Airedale Terrier with type-I von Willebrand disease (vWd), but lacking clinical signs of vWd, had normal platelet content of vwf:Ag (28 +/- 12 canine U/10(12) platelets), whereas a German Shorthaired Pointer with moderately severe type-II vWd and a mildly affected Doberman Pinscher with type-I vWd had only a trace or undetectable amounts of vWf:Ag in their platelets. The concentration of vWf:Ag in platelet lysates from the Doberman Pinscher with vWd remained undetectable when the platelets were isolated from the Doberman Pinscher's blood mixed with citrated plasma from dogs with normal plasma vWf:Ag concentration. In all 3 dogs with vWd, platelet fibronectin content was within the normal range.

Tissues from cattle that died of experimentally induced mucosal disease (n = 3), naturally acquired mucosal disease (n = 6), or naturally acquired chronic bovine viral diarrhea (n = 4) were examined. Consistent findings were lymphocytic depletion of lymphoid tissues, degeneration of myenteric ganglion cells, and mild adrenalitis. Intracytoplasmic viral antigen was detected in myenteric ganglia and in endocrine glandular cells. Noncytopathic virus was isolated from all cattle, and cytopathic virus was isolated from 12 of 13 cattle.

Viral RNA oligonucleotide fingerprinting was used to discriminate 3 cytopathic vaccine bovine viral diarrhea viruses (BVDV) grown in medium supplemented with serum contaminated with noncytopathic BVDV from the same 3 viruses grown in cell culture free of BVDV. Oligonucleotide tide fingerprinting also effectively discriminated between reference Singer BVDV, NADL BVDV, and New York-1 BVDV grown in BVDV-free noncontaminated or BVDV-contaminated cell cultures. Oligonucleotide fingerprint mapping of viral RNA maybe used to determine the purity of virus stocks, as well as that of BVDV vaccines.

Three doses of an alpha2-adrenoreceptor antagonist, atipamezole, were administered to reverse xylazine-induced sedation, bradycardia, and ruminal atony in calves. Once a week for 4 weeks, each of 6 calves was administered IV 1 treatment of:0.3 mg of xylazine/kg of body weight, followed in 10 minutes by 1 ml of 0.9% NaCl; 0.3 mg of xylazine/kg, followed in 10 minutes by 3 microgram of atipamezole/kg; 0.3 mg of xylazine/kg, followed in 10 minutes by 10 microgram of atipamezole/kg; or 0.3 mg of xylazine/kg, followed in 10 minutes by 30 microgram of atipamezole/kg. The order of the 4 treatments in each calf was selected at random. Xylazine alone caused lateral recumbency for 33.6 +/- 7.1 minutes (mean +/-SEM). Atipamezole administered at dosages of 3, 10, and 30 microgram/kg shortened xylazine-induced lateral recumbency to 20.5 +/- 3.0, 10.2 +/- 0.2, and 9.3 +/- 0.5 minutes, respectively. Calves given xylazine alone stood at > 60 minutes after the onset of recumbency. Atipamezole given at 3, 10, and 30 microgram/kg shortened the time from onset of lateral recumbency to standing to 40.2 +/- 6.9, 12.8 +/- 1.1, and 10.0 +/- 0.7 minutes, respectively. Drowsiness was found in calves given the lowest dosage of atipamezole (3 microgram/kg) after the calves stood. Atipamezole given at dosages of 10 and 30 microgram/kg reversed xylazine-induced ruminal atony in a dose-dependent manner. In addition, 30 microgram of atipamezole/kg reversed xylazine-induced bradycardia, but the lower dosages of this antagonist did not. Results indicated that 30 microgram of atipamezole/kg should be a useful antidote for xylazine overdose in cattle.

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 microgram/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 microgram/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q 24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 microgram/ml) for 100% of the treatment time if the animal is dosed q 6 h, 78% for dosing q 8 h, and 52% for dosing q 12 h. Therefore, we suggest 3 mg/kg, q 8 h or q 6 h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.

Ovine progressive pneumonia is caused by a lentivirus of known infectivity only for sheep and goats. Virus susceptibility of 11 other species of animals was examined. Species included cattle, chickens, deer, dogs, goats, hamsters, horses, mice, pigs, rabbits, and rats. Of these species, only goats and rabbits could be experimentally infected with the virus. The infection in rabbits was acute, and virus did not persist or induce antibody production as it does in sheep and goats. Sera obtained from several people working in close contact with the virus and from several wild species, with unknown exposure history, were tested for antibodies to viral antigens. All results were negative. Knowledge of the host range of this virus is important for scientific studies and for virus eradication programs.

Hyperlipemic serum and plasma samples often are received by clinical laboratories for endocrinologic analysis by radioimmunoassay. We designed a study to determine what effect, if any, hyperlipemia has on estimation of lipid-soluble hormone concentrations determined by solid-phase radioimmunoassays. Progesterone, testosterone, thyroxine, and cortisol concentrations were determined in canine plasma and serum with various degrees of lipemia. Samples of serum, heparinized plasma, and EDTA-treated plasma were obtained from blood collected from 4 female and 4 male Beagles by use of evacuated tubes. To induce hyperlipemia in vitro, IV fat emulsion was diluted in deionized water to produce 0 (water only), 33, 67, or 100% mixtures. Twenty microliters of each mixture then was added to the subsamples of serum and plasma from each dog. Hormone concentrations were determined, using validated radioimmunoassays. Triglyceride concentrations were determined by enzymatic assay. Addition of IV fat emulsion in vitro was an accurate and reproducible means of altering triglyceride concentrations in the samples. Triglyceride concentrations as high as 700 mg/dl had no effect on radioimmunoassays for progesterone, testosterone, and thyroxine in serum, heparinized plasma, or EDTA-treated plasma. Addition of 100% (but not 33 or 67%) fat emulsion reduced the mean cortisol concentration in heparinized plasma by 12% (P < 0.05). This severe hyperlipemia did not affect quantification of cortisol in serum or EDTA-treated plasma.