Over periods of 22 and 14 months, IgG antibody concentrations in serum samples obtained monthly from 14 mares and 19 foals, respectively, were measured by use of ELISA against antigens of the following environmental microbes: Aspergillus umbrosus, Penicillium brevicompactum, Rhodotorula glutinis, Absidia corymbifera, Aspergillus fumigatus, Humicola grisea, Micropolyspora faeni, and Thermoactinomyces vulgaris. The mares and foals were on pasture from early June until early October, then were stabled during the winter season until the following June. In the mares, increased antibody concentrations against most microbes were observed typically in midwinter and late spring when the horses were stabled; antibody concentrations against R glutinis, however, peaked in August. Concentrations differed between the summer and winter seasons and, in most instances, between 2 consecutive years and correlated with amounts of rainfall during the previous harvest season. In the foals, circulating passively acquired antibodies disappeared within 3 to 4 months after birth. During the first year of life, substantially increased autogenous antibody concentrations were observed only against R glutinis. Antibody concentrations against the other microbes increased gradually toward the end of the indoor season. In a group of foals transferred indoors in autumn, 6 weeks later than the other foals, antibody concentrations were lower when measured in December. Results supported the view that, to minimize exposure to microbial spores during the winter season, horses should be kept outdoors as much as possible and attention should be focused on improving the ventilation in stables and the quality of feeds and beddings.

Bovine pulmonary artery endothelial cells (BPAEC) were labeled with 3H-arachidonic acid. Exposure of the labeled BPAEC to Pasteurella haemolytica lipopolysaccharide (LPS) resulted in a time- and dose-dependent release of radioactivity. The release was inhibited by 5 mM indomethacin, but inhibition was not caused by less than or equal to 500 micromole indomethacin or hydrocortisone, which suggests that the release was caused primarily by a mechanism other than cyclooxygenase or phospholipase A2 metabolism of arachidonic acid. Pasteurella haemolytica LPS also caused increased adherence of bovine neutrophils to BPAEC through independent effects on both cell types. The increased adherence was inhibited by treatment of either cell type with cycloheximide or actinomycin D prior to LPS exposure, indicating that de novo protein synthesis was required in both cell types to promote the LPS-induced adherence. Lipopolysaccharide may be an important factor in neutrophil-mediated effects in pneumonic pasteurellosis by causing increased neutrophil adherence and, thus, the vascular sequestration of neutrophils. Together, these experiments provide additional evidence for the involvement of LPS in pneumonic pasteurellosis. Moreover, they provide evidence of LPS-induced endothelial activation, which could have broad ramifications in the inflammatory and immune responses of pneumonic pasteurellosis.

Newly hatched chickens were treated with the trichothecene mycotoxin, T-2 toxin, during the first day of life. Control chickens were treated with other agents known to cause immunosuppression-cyclosporine, cyclophosphamide, and aflatoxin. Chickens were infected on day 6 (5 days after treatment with T-2 toxin) by intraperitoneal inoculation with Salmonella typhimurium. Blood samples were collected from treated chickens (noninfected) and used to assess the responsiveness of blood lymphocytes to T-cell or B-cell mitogens, phytohemagglutinin, or lipopolysaccharide, respectively. The T-2 toxin had a profound negative effect on the ability of the chickens to resist salmonellosis, as measured by survival. However, the toxin effect in reducing phytohemagglutinin- and lipopolysaccharide-stimulated mitogenesis, though significant (P > 0.05), was not severe. Our data indicate a direct effect of T-2 toxin on native resistance to systemic salmonellosis, which was not accompanied by marked alteration in T- or B-cell responses to mitogenic stimulation.

The disposition of doxycycline hyclate after IV administration of 20 mg/kg of body weight was studied in 6 pigs. Median elimination half-life, estimated in 4 pigs, was 3.92 hours. Mean (+/- SEM) total body clearance was 1.67 +/- 0.18 ml/min/kg, and mean apparent volume of distribution at steady state was 0.53 +/- 0.04 L/kg. In 2 pigs, secondary peaks in the logarithmic serum concentration-time profile suggested discontinuous enterohepatic cycling, and precluded using these pigs in the pharmacokinetic analysis. The extent of doxycycline binding to serum protein was 93.1 +/- 0.2%. Serum or urine from 3 of the pigs was analyzed by use of photodiode array detection and mass spectrometry of a high-performance liquid chromatographic column effluent. These procedures documented lack of doxycycline biotransformation in pigs. It is concluded that, despite an elimination half-life shorter than that reported in other species, doxycycline may be a valuable antimicrobial drug for use in swine practice, pending the development of appropriate formulations.

Acute nephrotoxicosis was induced in ewes by daily SC administration of gentamicin. Activity of 3 urine enzymes, gamma-glutamyltransferase (GGT), beta-N-acetylglucosaminidase (AGS), and beta-glucuronidase (GRS), were measured during the development of aminoglycoside nephrotoxicosis. Measurements from timed, volume-measured urine samples were performed on days 0, 7, and 8. Measurements from urine samples obtained without volume measurement (spot samples) were performed daily. Urine GGT and AGS activities were high 3 days prior to detection of high serum creatinine concentration and 1.5 days before the appearance of casts in the urine sediment; values consistently remained in the abnormal range until termination of the study. High urine GRS activity was inconsistent and transient; serum GGT activity did not change during the course of the study. Urine GGT and AGS activities expressed as total excretion per unit time and body weight, enzyme activity per unit volume, and as ratio of urine enzyme activity to urine creatinine concentration were strongly correlated. Urine GGT and AGS, but not GRS activities, are suitable indicators of renal tubular cell damage in sheep with aminoglycoside nephrotoxicosis. Urine GGT and AGS activities indicate cellular changes occurring several days prior to the first indications of renal functional change.

Fenprostalene, a prostaglandin F2 alpha analog, can be used to induce parturition in swine. As part of the approval process for that indication, pharmacokinetic characteristics of the absorption and elimination of fenprostalene and the depletion of drug residues from the principal edible tissues of swine were studied. Blood samples, urine, and feces were collected from 8 gilts (body weight, 95 +/- 1.7 kg) for up to 72 hours after a single dose of 0.5 mg of 13,14-[3H]-fenprostalene in polyethylene glycol-400 was administered SC. At intervals of 24, 48, 72, and 168 hours after dosing, 2 gilts each were killed, and samples of liver, kidney, muscle, and abdominal fat were obtained for analysis. The mean (+/- SEM) maximal concentration of fenprostalene radioequivalents in plasma (0.41 +/- 0.05 nanogram-equivalents/ml; n = 8) was observed at 12 hours and decreased biexponentially, with half-lives of approximately 8 hours and 9 days. Mean cumulative recovery (n = 4) of the administered dose by 72 hours was 61.2 +/- 5.9% in urine and 18.5 +/- 2.6% in feces. The highest tissue fenprostalene concentration was in kidneys and liver, probably reflecting the role of those organs in excreting fenprostalene. Rates of depletion of fenprostalene equivalents from the injection site, kidneys, and liver were comparable with those previously observed in cattle. The composition of residue in the liver of 2 gilts slaughtered 12 hours after SC administration of [3H]-fenprostalene was examined in a second study. Results suggested that approximately 4% of the total residue was pharmacologically potent fenprostalene or the carboxylic acid form of fenprostalene. Approximately 29% of the residue was extensively degraded to acidic metabolites. The remaining 67% was bound, nonextractable material.

Pleural effusion was induced in 12 dogs by ligation of the cranial vena cava. Pleurodesis was attempted by injecting a solution of tetracycline hydrochloride into the pleural space of 8 dogs (4 dogs, 25 mg/kg of body weight; 4 dogs, 50 mg/kg) via bilateral thoracostomy tubes. In both groups, tetracycline was diluted in 40 ml of normal saline solution and 10 ml of 1% lidocaine before injection. Half of the solution (25 ml) was instilled in each hemithorax. Four control dogs were treated in the same manner with a solution of normal saline and lidocaine. Daily pleural fluid production was measured after the attempted pleurodesis. Thirty days after administration of the solution, each dog was euthanatized and necropsied. Surface area of pleural adhesions was measured. Tissues from regions of pleural adhesions and areas of parietal and visceral pleura not involved in adhesions were analyzed histologically. Formation of pleural fluid stopped in all but 1 control dog within 48 hours after injection of solution. This dog effused throughout the study. The resolution of effusion was not significantly (P < 0.05) different between the tetracycline-treated dogs and the control group. Although diffuse pleural adhesions were not induced in any of the dogs, significantly (P < 0.0027) more surface area of lung was adhered in dogs treated with the higher dose of tetracycline.

An experiment was conducted to determine whether balancing dietary crude protein for optimal rumen degradability would improve fertilization rate and quality of ova in lactating dairy cows. Thirty-eight Holstein cows in early lactation were fed 1 of 2 diets formulated to be isocaloric and isonitrogenous, containing 16% crude protein. Diet 1 contained 73% rumen degradable intake protein, whereas diet 2 contained 64% rumen degradable intake protein. The cows were induced to superovulate and were inseminated, and ova were recovered nonsurgically on postbreeding day 7. Ova were counted and classified as fertilized or unfertilized. Fertilized ova were scored as excellent, good, fair, poor, or degenerate. Unfertilized ova and poor and degenerate embryos were considered to be nontransferable ova and excellent, good, and fair embryos were considered to be transferable ova. There were no differences for mean number of fertilized, unfertilized, transferable, or nontransferable ova recovered from cows fed the 2 diets (P > 0.10). Mean percentage of fertilized ova recovered from cows was greater (P < 0.05) in those fed diet 2, compared with diet 1. Mean percentage of transferable ova recovered from cows tended to be greater (P = 0.06) in those fed diet 2, compared with diet 1. More cows failed to yield transferable ova (P < 0.05) when fed diet 1, compared with diet 2. Fertilization failure or early degeneration of embryos may occur in cows fed excess rumen degradable protein.

The carotid artery of clinically normal goats was examined, using duplex ultrasonography and arteriography. The diameter of the carotid artery was measured by use of two-dimensional ultrasonography and Doppler ultrasonography, respectively, before and after xylazine administration. The diameter of the artery was also measured by use of an arteriography technique in halothane-anesthetized goats. There was no significant difference between the mean diameter of the carotid artery measured by ultrasonography in conscious nonsedated goats and that determined by arteriography in goats under halothane anesthesia. On the other hand, ultrasonography of xylazine-sedated goats revealed an increase of carotid artery diameter of 20 to 30%. There was no change in the velocity of blood flow after xylazine administration.

Interleukin-1 (IL-1) is a protein secreted by stimulated cells of the monocyte-macrophage line, which has a number of important biologic activities. Interleukin-1 has been implicated in the induction and augmentation of the pathologic processes involved in arthritis and articular cartilage destruction. Horses develop osteoarthritis with a frequency and degree of severity similar to human beings. To further document the similarity of the osteoarthritic process in people and horses, the synovial fluid from 5 horses with clinical osteoarthritis was tested for IL-1 bioactivity. Interleukin-1 activity was found in all tested synovial fluids. Upon column chromatography, the synovial fluid-derived factor had a molecular weight consistent with that of IL-1 in other mammalian species. Ion exchange chromatography of osteoarthritic synovial fluid revealed the principal peaks of bioactivity to be in the fractions with isoelectric points of 7.2, 5.4, and 4.7, which are characteristic of IL-I. A considerable degree of homology between human and equine IL-1 was demonstrated by the cross hybridization of a human IL-1 beta cDNA probe with RNA derived from IL-1-producing equine adherent monocytes. These results indicate that equine IL-1 is in all of the osteoarthritic equine joints tested and that equine IL-1 has many of the characteristics of IL-1 isolated from other species.