Studies were undertaken to determine the efficacy of milbemycin oxime against the enteric adult stages of Trichinella spiralis and of albendazole against the muscle stage larvae in experimentally infected dogs and cats. Specific-pathogen-free Beagle pups (n = 6) and domestic shorthair kittens (n = 6) were inoculated with 7,500 first-stage larvae of Trichinella spiralis. Physical examination (including collection of blood and fecal samples) was performed weekly. During the first week after inoculation, all animals had mild gastrointestinal tract disturbances, but stages of T. spiralis were not observed in the feces. Beginning on postinoculation day (PID) 10, 3 pups and 3 kittens were treated with milbemycin oxime (1.25 mg/kg of body weight, PO, q 12 h) for 10 days. Muscle biopsy specimens were taken from dogs and cats on PID 26 and 29, respectively. Mean numbers of larvae per gram of muscle were 30.3 in the control and 37.7 in the treated dogs. Mean numbers of larvae per gram of muscle in the control and treated cats were 318.7 and 89.3, respectively. Two dogs and 2 cats were removed from the study at that time. The remaining animals, 2 each of the control and milbemycin oxime-treated animals, were given albendazole (50 mg/kg, PO, q 12 h) for 7 days starting at PID 31 and 34 in dogs and cats, respectively. Muscle biopsy specimens were again taken at PID 46 and 49, for dogs and cats, respectively; mean numbers of larvae recovered from muscle were 0.6 for dogs and 13.5 for cats.

Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxacaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 X that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites.

Pigs [9+/-1] weeks old) were inoculated with Streptococcus suis type 2, pseudorabies virus (PRV) or both. For each pig of groups A, B, and C the inoculum of S suis was 10(9) colony-forming units. For each pig of groups A, B, and D the inoculum of PRV was 5 X 10(3) TCID50 of either PRV strain 4892 (group A, n = 9) or PRV isolate B (group B, n = 9). The PRV strain 4892 is a highly virulent strain; isolate B causes mild clinical signs of infection in inoculated pigs. Group-C pigs (n = 9) were given S suis alone, and group-D pigs (n = 3) were inoculated only with PRV isolate B. Clinical signs of infection and development of lesions were readily seen in pigs of groups A, B, and C. Duration and severity of clinical signs of disease and lesions were reduced in pigs of group C, compared with those of the other 2 groups. Lesions, such as polyarthritis and fibrinous pericarditis, were more abundant and acute in the groups of pigs given mixed challenge exposure, compared with pigs inoculated exclusively with S suis type 2 (group C). The group of pigs inoculated with PRV isolate B alone did not manifest clinical signs of disease or lesions. Average daily gain for group-C pigs was higher, compared with that of other groups; the difference was statistically significant at P < 0.02 and P < 0.05 for groups B and D, respectively. Spread of S suis within the tissues of infected pigs was higher in pigs of groups A and B, compared with pigs of group C. Total number of isolations was 8, 15, and 7 for groups A, B, and C, respectively; S suis was isolated from more than 1 tissue specimen from some pigs. The rate of pigs carrying S suis was 4 of 4 in group-A, 7 of 9 in group-B, and 5 of 9 in group-C pigs. It was concluded that clinical disease associated with S suis type 2 was enhanced by concomitant infection with PRV and such effect was common to both PRV strains tested, the highly virulent strain and the strain with low virulence.

Two indirect ELISA containing outer membrane protein (OMP) and lipopolysaccharide (LPS) antigens from a field isolate of Salmonella choleraesuis var kunzendorf were developed and evaluated in experimentally infected and uninfected control pigs. Experimentally induced infection with S choleraesuis was successfully established in 10 pigs by oral inoculation with 10(8) organisms, and 3 pigs died of clinical salmonellosis at postinoculation (PI) weeks 1, 2, and 4. Swab specimens from tonsils, nostrils, and rectum of pigs were obtained for culture, and sera were evaluated at weekly intervals for 9 weeks after inoculation. The ELISA containing OMP and LPS antigens with either anti-swine IgG or protein albumin-to-globulin ratio (antiglobulin) conjugates were standardized for serologic evaluation. All 4 ELISA (2 OMP and 2 LPS) detected seroconversion by PI week 3 and had sensitivities and specificities of 97.8 and 88.8, 100 and 100, 95.6 and 88.8, and 93.3 and 72.5%, at their ideal cutoff points (negative mean optical density + 2 SD). There was excellent agreement between all 4 ELISA systems as determined by kappa values. Cultures of fecal, tonsil, and nasal swab specimens were positive for S choleraesuis until the fourth week of infection. Fecal swab specimens from 1 pig were positive for S choleraesuis until PI week 7. Persistent infection after antemortem culture results were negative was detected by all 4 ELISA, which indicated consistently high titers until the end of PI week 9. Conventional bacteriologic examination of intestines, mesenteric lymph nodes, bone marrow, lung, liver, spleen, and bile yielded positive results for S choleraesuis in the 3 pigs that died of clinical infection, whereas results were negative in the other 7 pigs infected by the end of PI week 9. Histologic examination of lung, liver, spleen, intestines, and mesenteric lymph nodes from the 3 pigs that died of S choleraesuis infection revealed severe ulceration and inflammatory cell infiltration.

Eight Holstein cows, 4 inoculated intracisternally in 1 quarter of the mammary gland with Escherichia coli and 4 noninfected controls, were administered ceftiofur sodium (3 mg/kg of body weight, IV, q 12 hours) for 24 hours, beginning at 14 hours after inoculation of infected cows. All challenge-exposed cows became infected, with mean +/-SEM peak log10 bacterial concentration in milk of 5.03 +/-0.69 colony-forming units/ml. The infection resulted in systemic signs (mean peak rectal temperature, 41.5 +/- 0.3 C; anorexia; signs of depression) and local inflammation (mean peak albumin concentration in milk, 7.89 +/- 1.71 mg/ml). Ceftiofur was detectable in milk from all challenge-exposed cows, compared with only 1 of 4 noninfected cows, and the mean period after inoculation that ceftiofur was detectable in milk was longer (P < 0.05) in infected (147.7 +/- 27.5 hours) than noninfected cows (1.3 +/- 1.3 hours). However, maximal ceftiofur concentration attained in milk for all cows was 0.28 micrograms/ml, and was 0.20 micrograms/ml or less for all but 2 milk samples collected for 10 days after challenge exposure. Mean serum concentration of ceftiofur peaked at 1.0 +/- 0.3 micrograms/ml and 0.7 +/- 0.1 micrograms/ml for infected and noninfected COWS, respectively. After each ceftiofur dose, mean peak and trough concentrations of ceftiofur in serum did not differ between groups; however, concentration of ceftiofur in serum was higher at 7 hours after each dose in noninfected cows, suggesting more rapid clearance of the drug in infected cows. Ceftiofur was not detected in serum (< 0.05 micrograms/ml) of any cow at or after 120 hours following inoculation of infected cows Storage of serum samples at -20 C for 3 weeks resulted in a 98.8% decrease in ceftiofur activity, compared with that in fresh serum samples. Eighty-seven percent of this loss occurred 30 minutes after mixing serum and ceftiofur; thus, about 13% of the original activity was lost in storage.

Four intrauterine treatment strategies were evaluated for effectiveness in mares that were confirmed to be susceptible to chronic uterine infection. Pretreatment samples were obtained at detection of estrus, and a genital strain of Streptococcus zooepidemicus was infused into the uterus when a preovulatory (> 35 mm) follicle was detected. At 12 hours after inoculation, mares were assigned to 1 of 4 selected treatment groups: autologous plasma, 100 ml (n = 5); potassium penicillin, 5 million U in 100 ml of phosphate-buffered saline solution (PBSS; n = 5); 10 mg of prostaglandin F2alpha in 100 ml of PBSS (n = 5); and large-volume lavage with normal saline solution (1,000 ml increments). A fifth group, treated with vehicle alone (100 ml of PBSS), served as a negative control (n = 7). All treatments were administered into the uterus. To assess the effectiveness of the treatment, samples for culture and cytologic examination were collected at 96 hours after bacterial inoculation. An effect of treatment was observed on the number of uterine neutrophils (P = 0.02) and growth of S zooepidemicus (P < 0.01). Intrauterine treatment with potassium penicillin, prostaglandin F2alpha, and large-volume uterine lavage significantly reduced the growth of S zooepidemicus (P < 0.01) as well as the number of neutrophils (P < 0.02). Autologous plasma reduced the number of neutrophils (P < 0.05), but not growth of S zooepidemicus. There was significant correlation between the number of uterine neutrophils and growth of S zooepidemicus for each treatment group (r = 0.57; P < 0.05).

Twenty-four horses were randomly allocated to 3 groups. Horses were anesthetized, subjected to a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls. Group-2 horses were subjected to 6 hours of low-flow colonic arterial ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline (BL) samples were collected, then low-flow ischemia was induced by reducing ventral colonic arterial blood flow to 20% of BL. All horses were monitored for 6 hours after BL data were collected. Blood samples were collected from the colonic vein and main pulmonary artery (systemic venous (SV) for measurement of plasma endotoxin, 6-keto prostaglandin F1alpha (6-kPG), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) concentrations. Tumor necrosis factor and interleukin-6 activities were measured in colonic venous (CV) serum samples. Data were analyzed, using two-was ANOVA, and post-hoc comparisons were made, using Dunnett's and Tukey's tests. Statistical significance was set at P < 0.05 Endotoxin was not detected in CV or SV plasma at any time. There was no detectable tumor necrosis factor or interleukin-6 activity in CV samples at any time. There were no differences at BL among groups for CV or SV 6-kPG, PGE2, or TXB2 concentrations, nor were there any changes across time in group-1 horses. Colonic venous 6-kPG concentration increased during ischemia in horses of groups 2 and 3; CV 6-kPG concentration peaked at 3 hours in group-3 horses, then decreased during reperfusion, but remained increased through 6 hours in group-2 horses. Systemic venous 6-kPG concentration increased during reperfusion in group-3 horses, but there were no changes in group-2 horses. Colonic venous PGE2 concentration increased during ischemia in horses of groups 2 and 3, and remained increased for the first hour of reperfusion in group-3 horses and for the 6-hour duration of ischemia in group-2 hors.

Efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ampicillin, was evaluated for treatment of experimentally induced pneumonia caused by beta-lactam-resistant Klebsiella pneumoniae. Infection was experimentally induced in 18 healthy weanling foals that were randomly allocated to 3 treatment groups: sulbactam plus ampicillin (S/A, 3.3 and 6.6 mg/kg of body weight, respectively), ampicillin (6.6 mg/kg), or vehicle only. Foals were treated daily for 7 days; the observer was unaware of treatment status. Compared with ampicillin and vehicle, treatment with S/A resulted in a statistically significant (P < 0.05) decrease in severity of pneumonia, with regard to bronchoalveolar lavage cytologic findings (decreased total cell and neutrophil numbers, and increased lymphocyte numbers) and extent of macroscopic lesions in lung tissue of the noninoculated regions. Marked trends toward improvement of S/A-treated foals were observed for quantitative results of bacteriologic culture of bronchoalveolar lavage fluid samples (P < 0.07), macroscopic pathologic features of the whole lung (P < 0.1), and histopathologic variables (P < 0.07), compared with ampicillin- and vehicle-treated foals. Treatment effects were not observed for radiographic, hematologic, and blood gas abnormalities that resulted from infection. In conclusion, the combination of sulbactam plus ampicillin was found to have synergistic effects in vivo, to reduce the extent and severity of experimentally induced grain-negative lung infection in foals.

Previous work had indicated that the 2 canine hookworms, Ancylostoma caninum and Uncinaria stenocephala, may differ in their susceptibility to treatment with milbemycin oxime. Thus, the study reported here was to examine the effects of this drug on concomitant infections in experimentally infected dogs. Twenty specific-pathogen-free Beagles were inoculated orally with 500 infective-stage larvae from a mixture of larval A caninum and U stenocephala. Quantitative fecal examinations were performed weekly, beginning the day of infection. The dogs were assigned to 2 equal groups, 1 group that received the compound and 1 that received a placebo. The dogs were treated on postinoculation days 30, 60, and 90. For A caninum, egg counts dropped precipitously after the first treatment, and no eggs of this species were found in the feces of any of the treated dogs after the second treatment. The treatments had no significant effect on the mean egg counts made on U stenocephala, although 2 dogs stopped passing eggs entirely after the second treatment. At necropsy, no A caninum were found in any of the treated dogs; the mean number recovered from the control-group dogs was 56.1. Significant difference was not found in the mean number of adult U stenocephala recovered from the treated and control groups (27.0 and 21.7, respectively).

Studies were conducted to ascertain in vitro effects and effects of percutaneous application (in vivo) of dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) on cholinesterase activities in bovine erythrocytes and plasma. Treatment in vitro of erythrocytes and plasma with DDVP resulted in concentration- and time-dependent inhibition of erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (ChE) activities. Mean (+/- SD) DDVP concentrations required to cause 50% enzyme inhibition were 15.7 +/- 3.3 muM and 43.1 +/- 5.7 muM for AChE and ChE, respectively; however, these values required to achieve this inhibition were markedly decreased with increasing incubation time. The inhibited AChE activity failed to be reactivated after incubation of erythrocytes with 2-pyridine aldoxime methiodide (2-PAM); however, limited reactivation of inhibited AChE and ChE activities was observed with excess concentration of 2-PAM. Percutaneous application of a DDVP-containing livestock spray on cattle also caused a marked decrease in the in vivo activities of AChE and ChE; however, the inhibited enzyme activities were reactivated rapidly after incubation with 2-PAM.