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.

Blood, serum, and plasma total calcium concentrations and plasma and serum ionized calcium concentrations were anaerobically determined by use of a calcium-specific electrode for samples obtained from 39 healthy horses. Mean (+/- SD) serum ionized calcium concentration was 6.6 +/- 0.3 mg/dl (1.6 +/- 0.1 mmol/L) and the mean serum ionized calcium percentage was 58.2 +/- 3.4%. Serum ionized calcium percentage was not significantly correlated with serum pH. Plasma ionized calcium percentage was weakly correlated with plasma pH (r = - 0.480; P less than or equal to 0.05). Ionized calcium concentration was determined in serum samples manipulated in vitro by additions of 1 to 80 microliter of 0.1N hydrochloric acid or sodium hydroxide to yield 6 to 10 pH values between 6.8 and 8.2. In all horses, the relationship between serum ionized calcium percentage and serum pH at these pH values was then examined by use of a repeated-measures multiple regression analysis. Correlations between serum ionized calcium percentage and adjusted serum pH value for each horse were highly significant (P < 0.05); however, analysis of pooled data from all horses indicated that a statistically significant relationship between serum pH and ionized calcium percentage did not exist. Lack of a significant relationship between these variables was most likely attributable to heterogeneity of variance of ionized calcium percentage among horses, reflecting variation in undefined biochemical constituents of serum that affect the equilibrium of calcium binding. When it is essential to evaluate the calcium status of a horse, direct measurement of serum ionized calcium concentration is recommended.

A genomic library to Eperythrozoon suis DNA was constructed in lambda gt11, and from this library, E suis clone KSU-2 was identified as a potential diagnostic probe. In hybridization experiments that used 100-microliter samples of blood collected in chaotropic salt solutions, the KSU-2 probe hybridized strongly with purified E suis organisms and blood samples from splenectomized swine that were parasitized with E suis. However, the probe under stringent conditions did not give radiographic indications of hybridizing with equine blood DNA, bovine blood DNA infected with Anaplasma marginale, canine blood DNA infected with Ehrlichia canis, feline blood DNA infected with Haemobartonella felis, or uninfected swine blood DNA.

Experiments were conducted to evaluate the effect of restricted feeding of a starter diet to suckling pigs (creep feeding) in a model of postweaning colibacillosis. The hypothesis that restricted creep feeding primes an intestinal allergic reaction to starter diet ingested after weaning was tested. Twenty-eight suckling pigs were fed a starter diet for 3 h/d on days 7, 8, and 9 after birth (creep-fed). Twenty-six suckling pigs were not fed the diet until 3 weeks of age (not creep-fed), when all pigs were weaned and given the starter diet. One day after weaning, 24 creep-fed and 22 not creep-fed pigs were inoculated with K88+ enterotoxigenic Escherichia coli, and 4 pigs in each group were kept as noninoculated controls. Among inoculated pigs (principals), 10 creep-fed and 12 not creep-fed pigs were found to be genetically resistant to K88+ E coli and remained healthy during the 6-day postinoculation period, as did the noninoculated controls. Eighteen (10 creep-fed and 8 not creep-fed) of the 24 genetically susceptible principals developed diarrhea after inoculation. There were no significant differences in the incidence and severity of diarrhea, amount of body weight loss, and mortality between creep-fed and not creep-fed susceptible principal pigs. Histologic examination of intestine from control pigs and principals that survived for 6 days after infection did not reveal any substantial morphologic difference between creep-fed and not creep-fed groups. In conclusion, creep feeding was not required for the production of diarrhea in this model. Creep feeding did not induce morphologic changes characteristic of an allergic reaction in the small intestine.

Pseudorabies virus (PRV) immediate-early (IE) protein is a nonglycosylated polypeptide localized in the nuclei of infected cells. The IE protein is a regulatory protein that is only synthesized during viral replication and is presented to the immune system of PRV-infected swine. Antibodies to the IE protein were demonstrated in swine with induced or naturally acquired infection. However, antiserum raised against purified IE protein could not neutralize PRV in vitro.

A mucosal lesion was created in the center of each test sinus of 6 mature, healthy, nonlactating Holstein cows by resecting a circumferential band of mucosa. Each lesion was then treated by implantation of strip grafts of autogenous oral mucosa, temporary silastic tube implant, or a combination of strip grafts and temporary silastic tube implant. All teats were evaluated for patency 6 weeks after treatment, and tube implants were removed through a second thelotomy incision. All teats were reevaluated for gross and radiographic patency 12 weeks after treatment, and teats were collected for histologic evaluation of lesions. All 4 teats treated with grafts only were obstructed at 6 and 12 weeks after treatment. Incomplete coverage of the lesion with mucosa was observed in all 4 teats. The major source of obstruction was proliferation of epithelium and keratin into the lumen. All 8 teats treated with temporary silastic tube implants alone were patent at 6 weeks after treatment, but were obstructed at 12 weeks after treatment. Foci of mucosa at the lesion site were detected in only 2 of the 8 teats. Obstruction resulted from proliferation of granulation tissue into the lumen. All 12 teats treated with grafts and a temporary tube implant were patent at 6 weeks after treatment and 11 of 12 were patent at 12 weeks after treatment, although marked luminal narrowing was evident in 9 of 11 teats. Partial to complete coverage of the lesion with mucosa was seen in all teats. Proliferative granulation tissue, epithelium, and keratin contributed to luminal narrowing in 10 of 11 patent teats. Bacteriologic culture of quarters from 6 of the 11 teats patent at the final evaluation yielded pathogens.

During the first part of a study, cats were inoculated with Cryptococcus neoformans via the following routes: intradermal, intranasal, IV, and intracisternal. Only use of the IV route of inoculation consistently induced disseminated cryptococcosis. In the second part of the study, disseminated cryptococcosis was experimentally induced in cats via IV inoculation of C neoformans. One month after inoculation, 3 cats were treated with ketoconazole (10 mg/kg of body weight/d) and 3 cats were treated with itraconazole (10 mg/kg/d) for 3 months. One of the ketoconzole-treated and 2 of the itraconazole-treated cats also had cryptococcosis of the CNS when treatment was begun. During treatment, serum cryptococcal antigen titer progressively decreased in all cats. Abnormalities in CBC values or the serum biochemical profile were not found in any cat during treatment. However, all ketoconazole-treated cats became anorectic and lost weight. Side effects were not seen in itraconazole-treated cats. During the 3-month posttreatment observation period, all cats remained healthy. At necropsy, histologic evidence of cryptococcosis was not found in the 3 ketoconazole-treated cats or in 2 of the itraconazole-treated cats. In the third itraconazole-treated cat, cryptococcal organisms were found in the kidneys.

A study was conducted to determine whether subcomponent proteins (previously identified as BCSP20, BCSP3l, and BCSP45, and the corresponding recombinant proteins rBCSP20, rBCSP31, and rBCSP45) that were recovered from the cell surface of Brucella abortus strain 19 were immunogenic and protective for mice when compared with Brucella cell surface protein (BCSP) and with a proteinase K-treated lipopolysaccharide (PKLPS) extracted from B abortus strain 2308. Protection was evaluated after challenge exposure with a virulent culture of B abortus strain 2308, using CD-1 or BALB/c mice or both inoculated with vaccines of various combinations and concentrations, with and without PKLPS or BCSP. Protection was assessed by enumeration of splenic colony-forming units, reduced mean splenic weight relative to controls, and the relative serologic responses (immune response) in an ELISA. The general results indicate that BCSP, PKLPS, BCSP20, and BCSP31 are immunogenic or protective or both. Protectiveness was not observed for each of the recombinant proteins; however, results from the combined recombinant protein vaccine study suggest the immunogenicity of the recombinant proteins. The apparent immune-inducing properties of BCSP20 and BCSP3l are thought to be attributable to the presence of an immunogenic and protective BCSP fraction (possibly lipopolysaccharide) still associated. Serologic results support our conclusion that each of the recombinant protein vaccines did not induce a protective response comparable to that of BCSP or PKLPS, even when the subcomponents were combined. Although the results suggest that the subcomponents of BCSP apparently induced partial protection, they are thought to be only a part of the antigens contained in BCSP that influence the serologic response. Our findings may serve as an experimental model to determine the mechanisms involved in the protective responses induced by Brucella antigens.

To investigate the cardiopulmonary effects of positive end-expiratory pressure (PEEP), values of 10, 20, and 30 cm of H2O, were applied to anesthetized, dorsally recumbent, ventilated ponies. After IV induction of general anesthesia, PEEP was superimposed on controlled ventilation with 100% oxygen, and changes in gas exchange and cardiac function were measured. Increasing values of PEEP in these ponies caused a linear increase in the mean (+/- SEM) functional residual capacity, from a control value (zero end-expiratory pressure) of 1.7 +/- 0.24 L to 2.2 +/- 0.31, 2.9 +/- 0.32 and 3.4 +/- 0.3 L at PEEP of 10, 20, and 30 cm of H2O, respectively (P < 0.05). Paralleling these changes, intrapulmonary shunt fraction decreased significantly (P < 0.05) from a control value of 12.9 +/- 0.5%, to 7.5 +/- 1.1 and 2.1 +/- 0.6%, at PEEP of 20 and 30 cm of H2O, respectively. Cardiac output was decreased by increasing values of PEEP, from control value of 11.7 +/- 1.56 L/min to 9.9 +/- 1.51, 8.8 +/- 1.33 and 5.62 +/- 0.56 L/min at PEEP of 10, 20, and 30 cm of H2O, respectively. Related to decreasing cardiac output, tissue oxygen delivery also decreased as PEEP was increased, from control value of 2.0 +/- 0.09 L/min to 1.8 +/- 0.07, 1.6 +/- 0.06, and 1.03 +/- 0.04 L/min at PEEP of 10, 20, and 30 cm of H2O, respectively. Thus, the effects of increasing values of PEEP in these ponies included increased functional residual capacity and arterial oxygenation, but marked reduction in cardiac output, resulting in no improvement or decrease in total oxygen delivery. Although PEEP is useful for improving arterial oxygenation, the deleterious cardiovascular effects should be anticipated or ameliorated by use of volume loading and/or inotrope administration.