The macrolytic lactone F28249-alpha was titrated in experimentally infected sheep and found to be highly effective against most of the common gastrointestinal nematodes as a single oral dose, given at a rate of 0.025, 0.05, or 0.1 mg/kg. Specifically, maximal activity was evident at even the lowest dosage against adult Haemonchus contortus, Ostertagia circumcinta, Trichostrongylus axei, and T colubriformis and L4 O circumcinta. Activity against Oesophagostomum columbianum was also high at all dosages, with a calculated ED95 of 0.029 mg/kg. Cooperia curticei was eliminated at 0.1 mg/kg, but control was erratic at the lower dosages. The greatest weakness of this compound was its activity against C oncophora. The activity against this parasite was weak (<less than or equal to 85%) at all dosages, and the dosage-response curve was flat, suggesting dosages substantially higher than those given would be necessary for high-order control of this species.

Absorption rate and plasma and fat disposition of lindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 microgram/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 microgram/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 microgram/g (ie, lower than the generally accepted tolerance level of 2 microgram/g).

High-performance liquid chromatography (HPLC) was used to determine the phospholipid (PL) composition of ovine, equine, bovine, porcine, and canine RBC membranes. Procedural modifications of established techniques provided for separation of 7 PL within a 15- to 20-minute sample run. Significant (P < 0.05) differences were detected in RBC membrane PL composition among the various species. The concern for physiologic properties associated with hemolysis and/or sedimentation rate must include evaluation of differences in the PL bilayer structure.

Hypochloremic metabolic alkalosis accompanied by hypokalemia and hyponatremia was induced experimentally in 7 adult sheep by diversion (loss) of gastric contents through an Ivan and Johnston cannula placed in the cranial part of the duodenum just distal to the pylorus. Cannula placement was easily accomplished, and cannulae were tolerated well by the sheep. Volume of effluent produced during the 60- to 120-hour period of diversion ranged from 7.7 to 14.9 L and tended to be greatest during the first 24 hours. All sheep became dehydrated, with mean PCV and plasma total protein concentration increases of 94.2 and 61.7%, respectively. Plasma chloride concentration decreased in linear fashion from a prediversion mean of 113 mEq/L (range, 111 to 117 mEq/L) to an end-point mean of 54 mEq/L (range, 45 to 65 mEq/L). Plasma sodium and potassium concentrations also decreased, though potassium concentration increased terminally. There were rapid increases in arterial blood pH and bicarbonate and base excess concentrations during the first 48 hours after diversion. However, during the final stages of diversion, sheep developed superimposed metabolic acidosis with increased plasma lactate concentration and high anion gap.

Pseudorabies virus (PRV), an alpha-herpesvirus, causes substantial economic losses in the swine industry and is currently the focus of eradication and control programs. Some of these programs rely on the ability of veterinarians to differentiate animals exposed to virulent strains of PRV from animals exposed to avirulent vaccine strains of PRV on the basis of a serologic response to nonessential glycoproteins that are deleted in some vaccine strains of PRV. Genetic recombination resulting in the creation of virulent strains of PRV with the same negative immunologic markers as vaccine strains could disrupt these programs. Two strains of PRV were coinoculated either into tissue culture or into sheep to facilitate recombination. Progeny viruses were selected to detect a specific recombinant phenotype. We were able to detect genetic recombination between vaccine strains of PRV following in vitro or in vivo coinoculation of 2 strains of PRV. The selected recombinants had marker-deleted phenotypes in strains with restored virulence genes. Increased virulence was observed in sheep after coinoculation of 2 avirulent vaccine strains of PRV.

Twenty-four isolates representing 6 species of Campylobacter were screened for plasmids. A large plasmid with an approximate molecular weight of 38 Mdal was detected in 5 C jejuni isolates originally recovered from diarrheic human beings, in one isolate of C coli recovered from diarrheic pigs, and in 1 isolate of C sputorum ssp mucosalis and 2 isolates of C hyointestinalis recovered from pigs with proliferative enteritis. One isolate of C coli and 1 isolate of C hyointestinalis contained an additional smaller plasmid with an approximate molecular weight of 1.6 Mdal; this plasmid was partially mapped by restriction endonuclease digestion. Fifteen Campylobacter isolates contained no detectable plasmids: 2 C coli, 2 C sputorum ssp mucosalis, 2 C fecalis, 1 C fetus ssp fetus, and 8 C hyointestinalis isolates. In summary, 37.5% of the Campylobacter isolates contained a 38-Mdal plasmid, with 8% having both 38 Mdal and 1.6-Mdal plasmids; 62.5% contained no detectable plasmids.

Renal electrolyte and net acid excretion were characterized during generation and maintenance of hypochloremic metabolic alkalosis in a ruminant model. Two phases of renal response with regard to sodium and net acid excretion were documented. An initial decrease in net acid excretion was attributable to increase in bicarbonate excretion with associated increase in sodium excretion. As the metabolic disturbance became more advanced, a second phase of renal excretion was observed in which sodium and bicarbonate excretion were markedly decreased, leading to increase in net acid excretion and development of aciduria. Throughout the metabolic disturbance, chloride excretion was markedly decreased; potassium excretion also decreased. These changes were accompanied by increase in plasma renin and aldosterone concentrations. There was apparent failure to concentrate the urine optimally during the course of the metabolic disturbance, despite increasing plasma concentration of antidiuretic hormone.

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.

Serologic evidence indicated that an episode of congenital abnormalities in sheep was caused by Cache Valley virus (CVV), a bunyavirus indigenous to the United States. To determine the teratogenic potential of CVV in sheep, fetuses were infected in utero between 27 and 54 days of gestation with an isolate (CK-102) obtained in 1987 from a sentinel sheep in San Angelo, Texas. The dams of these fetuses were euthanatized between 28 and 75 days after inoculation, and the fetuses were examined for malformations. Twenty-eight of 34 fetuses had congenital abnormalities, including arthrogryposis, hydranencephaly, mummification, reabsorption, and oligohydroamnion. Virus was isolated from the allantoic fluid of 11 of 17 fetuses euthanatized at less than 70 days of gestation. The virus-positive fetuses, which were all negative for CVV-neutralizing antibody, had lesions ranging from none to severe arthrogryposis and hydranencephaly. Virus was not recovered from the allantoic fluid of fetuses after 76 days' gestation when CVV-specific antibody could be detected in 5 of 8 fetuses examined. The 2 fetuses infected on days 50 and 54 of gestation appeared normal and 1 had antibody to CVV.

Viral RNA oligonucleotide fingerprinting was used to compare genetic relationships among pestiviruses originating from ovine or bovine host species. Ovine pestiviruses, including reference border disease virus and 2 border disease isolates originating from natural pestivirus infections of sheep, appeared to have a more distant genetic relationship among themselves than with certain bovine pestiviruses. A closer genetic relatedness was evident between border disease virus and 3 noncytopathic bovine pestiviruses, including Draper bovine viral diarrhea virus (BVDV), a BVDV isolate that originated from aborted bovine fetuses, and a virus that was isolated from the serum of a calf that had a chronic BVDV infection. Four noncytopathic bovine viruses, including Draper BVDV and 3 field isolates, were closely related. Reference Oregon C24V BVDV, a cytopathic virus, was closely related to only 1 of the 7 noncytopathic viruses in this study.