Cardiorespiratory effects of the combination of acepromazine maleate (ACP) and buprenorphine hydrochloride (BPN) were studied in 11 healthy, conscious dogs. Values for systemic and pulmonary artery blood pressure, cardiac output, arterial and venous pH and blood gas tensions, and invasive and noninvasive estimates of ventricular systolic function, preload, and afterload were obtained before sedation and after administration of each drug. Acepromazine maleate (0.1 mg/kg, IV) depressed cardiac function, compared with baseline values for unsedated dogs. Cardiac output decreased from a mean (+/- SD) value of 4.2 (+/- 1.5) L/min to 3.1 (+/- 0.8) L/min (P < 0.001), a change not attributed to heart rate. Pulmonary capillary wedge pressure decreased from 8.3 (+/- 4.2) mm of Hg to 6.5 (+/- 4.3) mm of Hg (P < 0.01), but mean right atrial pressure did not change. Left ventricular measurement of the maximal positive rate of pressure change (dP/dtmax) decreased from 2,668 (+/- 356)/mm of Hg/s to 2,145 (+/- 463) mm of Hg/s (P < 0.001), and ventricular stroke volume decreased from 43.2 (+/- 15.2) ml/beat to 32.3 (/- 8.6) ml/beat. Noninvasive indices of left ventricular function, ventricular shortening fraction, peak aortic velocity, and aortic average acceleration were decreased after ACP administration, but were not statistically different from baseline values. Mean systemic arterial blood pressure decreased from 121 +/- 12 mm of Hg to 96 +/- 13 mm of Hg 15 minutes after ACP administration (P < 0.001). Total systemic vascular resistance was not significantly different from the baseline value. Sequential administration of cumulative doses of BPN (0.005, 0.01, and 0.1 mg/kg of body weight, IV), initiated 15 minutes after administration of ACP, did not cause statistically significant depression of hemodynamic variables, except for heart rate, which decreased after BPN, and left ventricular dP/dtmax, which decreased slightly at the highest dose of BPN. Small, clinically insignificant changes in blood pH, venous bicarbonate concentration, and PaCO2 were observed after administration of ACP and BPN. Respiratory rate decreased from 60 +/- 48 breaths/min to 24 +/- 12 breaths/min, and sedation level was significantly (P < 0.05) increased from baseline values by administration of ACP. Sedation level was further increased by administration of BPN at the lowest dose (P < 0.05). The combination of ACP and BPN resulted in good to excellent sedation, but depressed ventricular function; however, most of the hemodynamic effects could be attributed to administration of ACP and withdrawal of sympathetic activity.

The Rice strain of pseudorabies virus (PRV) was intranasally instilled in pigs that were seronegative to PRV. Cells were scraped or brushed from tonsillar surfaces biweekly until pigs were euthanatized at either 10 or 16 weeks after infection. The DNA extracted from tonsillar cells or parenchyma were subjected to polymerase chain reaction analysis, using either a single set of oligonucleotide primers or nested primers from the PRV gII glycoprotein gene. Pigs became seropositive to PRV by 3 weeks after infection. The virus was isolated from the trigeminal ganglia and tonsils of pigs that were euthanatized or died 1 to 2 weeks after infection, but not from pigs that were euthanatized 10 or 16 weeks after infection. The PRV gene products were consistently detected in trigeminal ganglia and tonsils of all pigs at 1, 10, and 16 weeks after infection, and sporadically in the nasal mucosa, lymph nodes, and lungs of pigs that were euthanatized or died during the first 2 weeks after infection. Cells collected biweekly from tonsillar surfaces were mostly nucleated, squamous epithelial cells with fewer lymphocytes and neutrophils. Polymerase chain reaction analysis of DNA extracted from these cells revealed PRV DNA in a large proportion of the samples when sufficient cells were collected to provide 1 microgram of extracted DNA for use in the reaction mixtures. A second group of pigs had PRV strain 4892 intranasally instilled. The virus was isolated from tonsillar swab specimens until 3 weeks after infection. Tonsillar brushing specimens were collected biweekly until 14 weeks after infection. Some brushing specimens contained all nucleated, squamous epithelial cells, whereas other specimens contained a mixture of epithelial cells and up to 15% neutrophils, lymphocytes, and small mononuclear cells. Results of polymerase chain reaction analysis of DNA extracted from tonsillar cells collected 5, 11, and 14 weeks after infection were consistently positive for PRV gene products. Intact cells collected from tonsillar surfaces were placed in polymerase chain reaction mixtures with nested oligonucleotide primers from the PRV gII glycoprotein gene and were subjected to multiple amplification cycles. Afterward, the specificity of the amplified PRV gene products was determined by hybridization procedures, using a virus-specific oligonucleotide probe. Most nucleated, squamous epithelial cells stained positive for PRV DNA, suggesting that these cells were the primary source of PRV gene products in tonsillar brushing specimens.

Once-daily administration of aminoglycosides may be a safe and effective therapeutic regimen, on the basis of the microbiologic and pharmacokinetic characteristics of these antibiotics. This study was designed to determine serum and tissue concentrations following IV administration of gentamicin, at dosages of 6.6 mg/kg of body weight, every 24 hours, and 2.2 mg/kg, every 8 hours, for 10 days in adult horses. Nephrotoxicosis from these dosage regimens also was compared, and microbiologic effects, including postantibiotic effects, were determined with various concentrations of gentamicin against an equine clinical isolate of Pseudomonas aeruginosa. Treatment at the 6.6-mg/kg dosage resulted in maximal serum concentrations (77.93 +/- 19.90 micrograms/ml, mean +/- SEM) and area under the concentration-vs-time curves (83.79 +/- 14.97 micrograms.h/ml) that were significantly (P < 0.05) greater than those following treatment at the 2.2-mg/kg dosage (5.05 +/- 0.50 micrograms/ml and 6.03 +/- 0.66 micrograms.h/ml, respectively). Nephrotoxicosis was not induced with either dosage regimen, and postantibiotic effects were prolonged with a higher gentamicin concentration. This study provided evidence to support the use of once-daily gentamicin treatment in adult horses.

Porcine fetuses were exposed in utero to porcine reproductive and respiratory syndrome virus (PRRSV) at stages of gestation ranging from 34 to 85 days and examined 17 to 31 days later to determine the effect of gestational age on fetal susceptibility. For each of the 8 litters tested during the study, all of the fetuses of 1 horn of the uterus were exposed to virus by intraamniotic injection; those of the other horn were exposed similarly to a sham inoculum that consisted of sterile cell culture medium. Viral infectivity titers associated with fetal tissues collected at necropsy indicated that, regardless of gestational age, the virus had replicated in fetuses exposed intraamniotically. In addition, virus had also spread and replicated in sham-inoculated littermates in 3 litters. On the basis of these findings it appears that there may be little or no temporal difference in fetal susceptibility to infection with PRRSV. If so, the lack of early fetal death as a commonly recognized feature of naturally occurring cases of PRRS may be due to a greater resistance of early gestational fetuses to the lethal effects of PRRSV, as suggested by this study, and/or a greater likelihood of transplacental infection during late gestation.

To measure the concentration of serum amyloid A (SAA) protein in horses a sensitive and highly reproducible sandwich (ELISA) was established, using affinity purified SAA antibody. Results of the ELISA were found to have a high correlation (r = 0.95) with those of the single radial immunodiffusion test. Equine SAA concentration was measured by use of this ELISA. In clinically normal horses, the concentration of SAA was high immediately after birth to 2 weeks of age. After that, SAA concentration had periodic fluctuations in the range of approximately 10 to 30 microgram/ml. Mean (+/- SD) concentrations of SAA in foals (less than or equal to 12 months old) and adult horses (greater than or equal to 18 months old) were 21.23 +/- 12.20 and 14.93 +/- 9.07 microgram/ml, respectively. In mares during the perinatal period, SAA concentration remained stable within the reference range before parturition. It increased quickly after delivery, and reached a peak value of 101.29 +/- 98.82 microgram/ml on postpartum day 3, then began to decrease, at postpartum week 2, to the reference range by the end of postpartum month 1. In horses with experimentally induced inflammation, SAA concentration increased quickly and reached approximately four- to 40-fold increase over the pretreatment value on day 1 and remained high on days 2 to h after treatment. It then returned to the baseline value by 2 to 4 weeks in association with disappearance of local signs of inflammation. The SAA concentration was high in most horses with clinical signs of inflammation. It was concluded from these data that this ELISA is sensitive and reliable for measuring SAA in horses.

To study their role in sulfate reduction, anaerobic bacteria were cultured from rumen fluid samples of cattle fed high-carbohydrate, short-fiber diets with and without added sulfate. The steers fed the diet with added sulfate developed polioencephalomalacia. Microbiological methods included colony-type profiles, molybdate sensitivity, presence of desulfoviridin, sulfate reduction rates of pure and mixed cultures, and incubation time effects on sulfate reduction. Colony-type profiles indicated decreased diversity, but no relative change in numbers of sulfate-reducing bacteria in rumen fluid from cattle fed diets with and without added sulfate. Thirteen bacterial isolates were selected for further study on the basis of colony type, sulfate-reducing activity, and growth in lactate, sulfate, and yeast extract media. Seven of the isolates had Desulfovibrio-like characteristics (ie, they were gram-negative, motile rods that reduced sulfate, were inhibited by molybdate, and contained the pigment desulfoviridin). The remaining 6 isolates were gram-negative, nonmotile rods. Four of these released sulfide from cysteine, and 2 generated only limited amounts of sulfide from sulfate or cysteine. The 7 sulfate-reducing isolates generated sulfide in rumen fluid broth medium at greater rates than those observed in fresh rumen fluid. Sulfate reduction could be sustained in cultures for prolonged incubation times if the gas phase containing hydrogen sulfide was replaced at frequent intervals. Variations in the amount of sulfate reduced by the pure cultures were most pronounced at short incubation times. Sulfate reduction was not inhibited in mixed cultures of sulfate-reducing and nonsulfate-reducing bacteria.

Topically applied 4% timolol, 4% timolol combined with 2% pilocarpine, 6% timolol, and 6% timolol combined with 2% pilocarpine were evaluated in clinically normal Beagles and Beagles with glaucoma. The drugs were instilled twice daily for 5 days. Changes in intraocular pressure (IOP), pupil size, and heart rate were recorded on days 1, 3, and 5 at 0, 2, 5, and 8 hours, starting at 8:30 AM. In clinically normal dogs, 4 and 6% topically administered timolol did not cause consistent reductions in IOP; however, with addition of 2% pilocarpine, IOP was consistently lower. In the Beagles with glaucoma, 4 and 6% timolol and, to a greater extent, 4 and 6% timolol combined with 2% pilocarpine lowered IOP. The combinations lowered IOP and reduced pupil size consistently. In all test groups, either 4 or 6% topically applied timolol caused approximately 10% decrease in mean heart rate.

Objective--To evaluate the effects of diethylstilbestrol (DES) or alpha-zearalanol (zeranol) on fetal development, gestation duration, and number of offspring. Design-Study effects of prenatal administration of DES or zeranol on various pre- and perinatal variables in an experimental group of mice, compared with effects in a control group. Animal--Pregnant NMRI mice. Procedure--Diethylstilbestrol or zeranol (150 mg/kg of body weight) or vehicle (controls) was administered sc to pregnant mice on days 9 and 10 of gestation. Fetuses from pregnant mice of each group were counted and weighed, and their size and head length were recorded. Additional pregnant mice delivered their fetuses naturally, and pups from each group were counted and their sex was determined. At the end of gestation, abortions were evaluated. All data were statistically analyzed. Results--Mean number of fetuses was significantly lower (P < 0.0001) in DES-treated (4.59 +/- 0.48) than in control mice (8.33 +/- 0.49). Both estrogenic substances significantly reduced fetal size and weight (P < 0.0001), compared with control mice. Diethylstilbestrol significantly increased abortion frequency (P < 0.0001) and gestation duration (P < 0.0001), compared with values for control mice. A reduced number of live pups (P < 0.0001) from pregnant mice administered DES (5.48 +/- 0.38) or zeranol (5.97 +/- 0.49) was observed, compared with control mice (8.52 +/- 0.50), because of reduced number of male offspring (P < 0.0001). Conclusions--Diethylstilbestrol or zeranol administered during mid-pregnancy leads to decreased fetal weight and size and lower numbers of male offspring at birth. Likewise, DES induced a significant increase in abortions and gestation duration.

The bioequivalency of 2 gondatropin-releasing hormone (GnRH) preparations, gonadorelin diacetate tetrahydrate and gonadorelin semicarbonate, was compared on the basis of luteinizing hormone (LH)-releasing ability of the 2 products in diestrous dairy cows. Twenty-four cycling, nonlactating Holstein cows were subjected to a double prostaglandin estrus synchronization treatment to simultaneously control stage of the estrous cycle and time factors as potential variables effecting LH responses to the treatments being studied. Circulating progesterone concentration was determined to verify stage of cycle at strategic times throughout the study. Twelve days after the second prostaglandin treatment, all cows were randomly assigned to 1 of 2 groups (n = 12). Each group of 12 cows received single doses (100 microgram) of either GnRH preparation at the start of each test period in a 2-period crossover design. Serum samples were obtained prior to and at 12 times (10, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1,440 minutes) after treatment and were assayed to determine circulating LH concentration. Significant difference between the 2 GnRH products was not found with respect to: mean concentration of LH in the blood during the 24 hours after treatment; maximal LH concentration; time from treatment to maximal LH concentration; and area under the LH concentration curve from time 0 through each of 7 times after treatment (0.5. 1, 1.5, 2, 4, 8, and 24 hours). These data confirm the bioequivalency of the 2 GnRH products.

Pharmacodynamic variables of enrofloxacin were investigated in a neutropenic mouse Escherichia coli and staphylococcal thigh infection model. Enrofloxacin pharmacokinetics in clinically normal mice and dogs were compared to confirm that doses evaluated in the mouse model would include enrofloxacin doses appropriate for use in dogs. Mice were made neutropenic by treatment with cyclophosphamide and injected in the thigh muscle with approximately 10(6) colony-forming units of E. coli (n = 2) or a staphylococcal (n = 2) clinical isolate. Enrofloxacin dosages tested ranged from 0.78 to 50 mg/kg of body weight and 6.25 to 200 mg/kg in the E. coli and staphylococcal infection trials, respectively. In each 24-hour dosage trial, enrofloxacin was administered SC as a single dose or in divided doses given every 3, 6, or 12 hours. Comparison of log(10) colony-forming units per thigh muscle in untreated control mice and mice treated with enrofloxacin was used as a measure of efficacy. Two-way ANOVA was used to determine that the enrofloxacin total dose, but not the dose frequency, was significant in determining drug efficacy. Pharmacokinetic values analyzed by use of multivariant stepwise linear regression analysis indicated that the area under the concentration-time curve, but not time above minimum inhibitory concentration, was significant in predicting efficacy of enrofloxacin treatment. We conclude that enrofloxacin killing of E. coli and staphylococci is concentration dependent and not time dependent.