Objective-To measure effects of Escherichia coli O149:F4-induced diarrhea on water consumption and pharmacokinetics of amoxicillin after administration in drinking water. Animals-24 recently weaned 24- to 28-day-old crossbred pigs. Procedure-10 pigs were inoculated with E coli O149:F4; all 10 pigs subsequently developed diarrhea. Pigs were medicated by administration of amoxicillin in the drinking water (0.75 mg/mL) for a 4-hour period on 2 consecutive days. Fourteen age-matched noninfected healthy pigs (control group) were medicated in a similar manner. Blood samples were obtained from both groups daily, and plasma concentrations of amoxicillin were analyzed by use of high-performance liquid chromatography. Results-Diarrhea reduced the area under the plasma concentration-versus-time curve (AUC) and maximum plasma concentration (C(max)) of amoxicillin on the first day of medication by 56% and 63%, respectively. The AUC of amoxicillin on the second day of medication for diarrheic pigs did not differ significantly from that of control pigs on the first day of medication. Conclusions and Clinical Relevance-E coli-induced diarrhea reduced the AUC of amoxicillin and time that plasma concentration of amoxicillin was > 0.025 microgram/mL and, hence, less likely to have a therapeutic effect on the first day of administration in drinking water. On the assumption that plasma concentrations may indirectly reflect concentrations at the site of infection, analysis of our results suggests that higher doses of amoxicillin may be appropriate for administration in drinking water during a 4-hour period on the first day that pigs have diarrhea attributable to E coli O149:F4.

Objective-To evaluate canine histiocytic sarcoma cell lines and tumor samples for dysregulation of the Kit/stem-cell factor (SCF), Flt3/Flt3 ligand (Flt3L), and Met/hepatocyte growth factor (HGF) receptor tyrosine kinase signaling pathways, as these are known to contribute to the differentiation and survival of normal dendritic cells as well as malignant transformation of dendritic cells in mouse models. Sample Population-4 histiocytic sarcoma tumor cell lines and 35 formalin-fixed histiocytic sarcoma specimens obtained from dogs. Procedure-Histiocytic sarcoma cell lines were evaluated for expression of Kit/SCF, Flt3/Flt3L, and Met/HGF by use of reverse transcriptase-PCR procedures. Histiocytic sarcoma cell lines and tumor samples were evaluated for mutations in Kit, Flt3, and Met by use of PCR analysis of genomic DNA, followed by both sequencing and fluorescent PAGE for deletions or internal tandem duplications. The ability of the multitargeted split-kinase inhibitor SU11654 to block proliferation and induce apoptosis of histiocytic sarcoma cell lines was also evaluated. Results-No mutations in Kit, Flt3, and Met were identified in any of the cell lines or tumor samples evaluated. Furthermore, SU11654 did not induce cellcycle arrest or apoptosis of histiocytic sarcoma lines, even at supratherapeutic doses. Conclusions and Clinical Relevance-These data suggest that dysregulation of Kit/SCF, Flt3/Flt3L, and Met/HGF signaling pathways is unlikely to occur in histiocytic sarcomas of dogs and that inhibitors of the Kit, Flt3, and Met pathways are unlikely to provide clinical benefit to dogs with histiocytic sarcomas.

Objective-To determine the susceptibility of strains of Pasteurella multocida subsp multocida isolated from lung specimens of pigs with pneumonia to 20 antimicrobials and to evaluate the emergence of resistance to those antimicrobials in Spain during the past 2 decades. Sample Population-63 isolates recovered from 1987 to 1988 and 132 isolates recovered from 2003 to 2004. Procedure-A broth microdilution method was used to determine minimal inhibitory concentration (MIC) range and values for MIC50 and MIC90. Resistance of a strain to an antimicrobial agent was determined by use of the breakpoint value when available. Results-Isolates were generally susceptible to penicillin, ampicillin, ceftiofur, gentamicin, apramycin, neomycin, spectinomycin, chlortetracycline, erythromycin, tilmicosin, enrofloxacin, and florfenicol, and most isolates were resistant to clindamycin, tylosin tartrate, and tiamulin regardless of the time period. A substantial increase in resistance to sulfachlorpiridazine, sulfadimethoxine, sulfathiazole, and trimethoprim-sulfamethoxazole was observed, and a minor increase in resistance to oxytetracycline was also detected. Several multiresistance patterns were observed, most frequently among isolates recovered in the 2003 to 2004 interval. Conclusions and Clinical Relevance-Ceftiofur, florfenicol, and enrofloxacin are recommended for treatment of infections caused by P multocida subsp multocida in Spain. Increased frequency of resistance to oxytetracycline and sulfonamide drugs may be a contraindication for their use.

Objective-To compare the urodynamic and morphologic effects of the administration of estriol alone and in combination with phenylpropanolamine on the lower portion of the urogenital tract in female dogs. Animals-3 sexually intact and 3 spayed female Beagles without urinary incontinence. Procedure-Dogs received estriol (2 mg, PO) once daily for 7 days followed by estriol (2 mg, PO) and phenylpropanolamine (1.5 mg/kg, PO) once daily for 7 days. Urethral pressure profilometry, diuresis cystometry, and vaginourethrography were performed before treatment (day 0) and at days 7 and 14. The maximum urethral pressure (MUP) and closure pressure (MUCP), urethral functional and anatomic profile lengths, integrated pressure (IP), plateau, distance before MUP, maximum meatus pressure, threshold pressure, threshold volume, compliance, urethral length, and vaginal length and width were measured. Results-Before treatment, no urodynamic differences were observed between the 2 groups; however, vaginal length and width were significantly shorter in spayed dogs. Compared with day 0 values, estriol treatment significantly increased MUP, MUCP, and IP values at day 7, but at day 14, this effect decreased despite phenylpropanolamine administration. No morphologic changes from baseline were detected after either treatment in any dog. Conclusions and Clinical Relevance-Data suggest that estriol mainly acts on the urethral sphincter mechanism by increasing urethral resistance in sexually intact and spayed female dogs without urinary incontinence. Administration of estriol and phenylpropanolamine did not increase the urethral resistance more than estriol alone. The urodynamic effects of estriol in female dogs with urinary incontinence remain to be elucidated.

The effect of a novel bovine mastitis trivalent vaccine, containing Staphylococcus aureus capsular polysaccharide type 5 (T5), 8 (T8), and 336 (T336), on lymphocyte subpopulations, antibody production, and neutrophil phagocytosis was evaluated. Twenty pregnant heifers were immunized with either the trivalent alone, trivalent emulsified in Freund's incomplete adjuvant (FICA), trivalent in aluminum hydroxide, or adjuvant only (FICA). Immunization was done 30 d before the expected calving date followed by 2 boosts in a 2-week interval. Compared to FICA, serum antigen-specific immunoglobulin (Ig)G1 and IgG2 were significantly increased in all the vaccinated groups before parturition and sustained until 3 wk postpartum. In comparison with the trivalent alone, formulation with either adjuvant enhanced production of IgG2, but not IgG1. Immune sera, which contained the highest amount of antibodies, slightly increased neutrophil phagocytosis to the 3 serotypes of killed S. aureus, but most of the differences were not significant due to large variation between the cows. The percentage of CD4+ lymphocyte was significantly higher in vaccinated groups than that of FICA 4 wk after the primary immunization. In comparison with FICA, cows inoculated with trivalent vaccine and adjuvants had an increased percentage of CD8+ lymphocytes at 2 time points, 2 wk before and after calving. Our results indicated that the whole cell trivalent vaccine, with or without adjuvants, is able to elicit antibody responses specific to the 3 capsular polysaccharide antigens. The increase of T8-specific IgG2 was more noticeable when the vaccine was emulsified with adjuvants.

Objective: To evaluate the genetic relatedness and antibiotic sensitivity profiles of Campylobacter coli isolates from sows and piglets housed in an integrated swine production facility. Sample Population: Ninety-nine isolates of Campylobacter coli were collected from 3 sows (Yorkshire-Landrace) and 18 piglets (Yorkshire-Landrace X Duroc or Hampshire) housed in a common farrowing barn. Procedure: When piglets were weaned (21 day of age) fecal samples were collected for the sows and rectal samples were collected from the piglets. Isolation of Campylobacter coli was performed using an enrichment broth and restrictive media under microaerophilic conditions. Results: The Campylobacter coli isolates segregated into 20 ribogroups and exhibited 32 antibiotic susceptibility profiles. The Ribogroup (224-373-S-5) contained 35 isolates from eleven animals. Thirty-eight percent of the animals exhibited a single ribogroup, while 10% of the animals exhibited four ribogroups. No discernible pattern of ribogroup relatedness was observed among the sows and piglets or among littermates. Conclusion: The data suggests a high level of diversity in both ribotypic patterns and antibiotic sensitivity profiles among the Campylobacter coli isolated from related pigs housed in a single facility. Further, no evidence was found for a direct transfer of specific Campylobacter coli ribotypes from a sow to her piglets.

Effects of 2 drugs commonly used for chemical restraint of cattle were evaluated for their effect on laryngeal and pharyngeal anatomy, function, and response to stimuli. Eighteen adult Jersey cows, free of respiratory tract disease, were studied. Cows were assigned at random to 1 of 3 treatment groups. Endoscopic evaluations were performed before and at a predetermined time interval after administration of each drug. Responses to stimuli were evaluated by stimulating 7 preselected sites (epiglottis, left and right arytenoid cartilages, left and right vocal folds, and left and right dorsolateral pharyngeal walls) with a closed, transendoscopic biopsy probe. Xylazine HCl (0.05 mg/kg of body weight, IV) was administered to group-1 cows (n = 6), and endoscopy was repeated 5 minutes after administration of the drug. Xylazine (0.07 mg/kg, IV) was administered to group-2 cows (n = 6), and endoscopy was repeated 5 minutes after administration of the drug. Acepromazine maleate (0.035 mg/kg, iv) was administered to group-3 cows (n = 6), and endoscopy was repeated 10 minutes after administration of the drug. Responses to stimuli were scored as brisk (0), moderate (1), slow (2), and absent (3). Scores for responses to stimuli were compared, using the Wilcoxon signed-rank test for data within groups, and a general linear models procedure, using the Kruskal-Wallis test between groups. Interobserver agreement rates were generated for each group. A value of P<0.05 was considered significant. Xylazine profoundly changed laryngeal sensitivity and function at both dosages. The corniculate processes of the arytenoid cartilages were observed to be in a markedly adducted position after sedation. Response to stimuli was significantly (P = 0.03) slower than normal after sedation, using both dosages. Displacement of the soft palate dorsal to the epiglottis was persistent in 50% of the cows after stimulation tests subsequent to sedation with xylazine. Acepromazine had a mild effect on laryngeal sensitivity and function. The corniculate processes of the arytenoid cartilages were observed in paramedian position after sedation. Acepromazine did not significantly affect responses to stimuli. Effects of sedation on responses to stimuli were not significantly different for groups 1 and 2. However, effects for group 3 were significantly different from those for groups 1 and 2 (P = 0.006 and 0.004, respectively). Endoscopic evaluation of the proximal portion of the respiratory tract of cattle should be performed without sedation, when possible. If sedation is required to facilitate restraint for endoscopy, acepromazine maleate is recommended over xylazine on the basis of results of this study.

Eighteen strains of Escherichia coli serogroup O115:K"V165" isolated from 1- to 8-week-old pigs with diarrhea were tested for toxigenicity, pathogenicity in pigs and mice, serum resistance, mannose-resistant hemagglutination (MRHA), F165 and other surface antigens, colicin V (Col V), aerobactin, and biotype. Twelve strains were positive for heat-stable enterotoxin (STb), MRHA-negative, and F165-negative; 5 strains were enterotoxin-negative, MRHA-positive, and F165-positive; and 1 strain was MRHA-positive, but F165- and enterotoxin-negative. Six of the 12 STb-positive strains moderately colonized the ileum of newborn colostrum-deprived pigs within 24 hours after inoculation. Two of the colonizing strains were able to induce watery diarrhea. All 12 STb-positive strains were nonpathogenic for adult mice and were serum-sensitive; 11 of 12 were Col V-negative, 9 of 12 did not produce aerobactin, and 10 of 12 belonged to biotypes other than 1 or 2. All 6 enterotoxin-negative strains colonized the small and large intestines, associated with peritoneal serosal surfaces, and induced septicemia and polyserositis in newborn colostrum-deprived pigs 1 to 2 days after inoculation. In contrast, 3 STb-positive strains poorly colonized the intestines and did not induce septicemia in pigs at 3 days after inoculation. All 6 enterotoxin-negative strains were Col V-positive, produced aerobactin, and belonged to biotype 1 or 2. Of the 5 enterotoxin-negative, F165-positive strains, only 4 were pathogenic for intraperitoneally inoculated adult mice and were serum-resistant. The enterotoxin-negative, F165-negative strain was neither serum-resistant nor mouse-pathogenic. O-agglutinable mutants of the mouse-pathogenic strains were, for the most part, no longer pathogenic for adult mice, although these strains remained unchanged for biotype and production of MRHA, F165, and Col V, and 3 of 4 mutant strains were serum-resistant. Thus, E coli strains of the same serogroup isolated from diarrheic pigs may cause either intestinal or extraintestinal disease upon reinoculation of pigs, depending on the virulence attributes produced by the strains.

The Langendorff isolated heart preparation was adapted to determine the effect of furazolidone (0.5 and 2 migrogram/ml of perfusate) on hearts of 3-week-old broiler chickens. Following 115 minutes of perfusion, both concentrations of furazolidone caused approximately a two-fold increase in myocardial vascular resistance and a six-fold increase in myocardial vascular resistance and a six-fold increase in lactate dehydrogenase release into the effluent fluid, compared with a control perfused group of isolated hearts (P less than 0.01). Ultrastructural alteration differences were not found between the drug-treated and control groups. It was concluded that: (i) furazolidone, at concentrations only moderately above therapeutic plasma concentrations, caused detrimental changes in myocardial vascular resistance and lactate dehydrogenase release and (ii) the isolated chicken heart preparation is an example of a cost-effective, reliable laboratory tool for screening potential cardiotoxins.

An experimental chlorate product (ECP) developed by the United States Department of Agriculture has been shown to have bactericidal effects against enteropathogens such as Escherichia coli. In studies with broilers and pigs, the bactericidal activity of ECP was enhanced by prior adaptation of gastrointestinal microflora to nitrate. The objective of this study was to examine the effects of nitrate adaptation on the bactericidal activity of ECP against E. coli in Holstein steers. Results indicate that ECP was effective at reducing E. coli. However, ECP did not reduce E. coli in a dose-dependent manner, indicating that the highest ECP dose provided in this study exceeded that needed to be efficacious. Adapting gastrointestinal microflora with nitrate prior to feeding ECP did not improve efficacy of ECP against E. coli. Rapid reduction of nitrate in the rumen is implicated as a possible explanation for why adaptation to nitrate did not enhance the bactericidal effects of ECP in cattle.