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Pharmacokinetics of sulfadiazine/trimethoprim in neonatal male calves: effect of age and penetration into cerebrospinal fluid
1989
Shoaf, S.E. | Schwark, W.S. | Guard, C.L.
Sulfadiazine (SDZ)/trimethoprim (TMP; 30 mg of SDZ/TMP/kg of body weight) was given IV to the same 6 male calves at 1, 7, and 42 days of age and to 2 additional calves at 7 days of age. Serum concentrations of SDZ and TMP were best represented by a 2-compartment open model, but in 42-day-old calves, CSF concentrations of both drugs were best represented by a 1-compartment open model with first-order input. Between 1 and 42 days of age, the elimination half-life (t1/2(beta)) of SDZ decreased from 5.7 to 3.6 hours, and total body clearance (CLtot) increased from 1.43 to 1.88 ml/min/kg; the area under the curve (AUCo leads to x) decreased from 291.5 to 225.4 mg/L.h. The distribution coefficient (Vd(area)/kg of body weight) decreased with age, changing from 0.72 to 0.59 L/kg, between 1 and 42 days of age. Therapeutic concentrations of SDZ in serum (greater than 2 micrograms/ml) were maintained for 24 hours in 1-day-old calves and for about 15 hours in 7- and 42-day-old calves. The elimination rate of TMP increased about 9-fold; t1/2(beta) was 8.4, 2.1, and 0.9 hours, respectively, at 1, 7, and 42 days of age. Other values also reflected an increase in TMP elimination rate with age: CLtot increased from 2.8 to 12 to 28.9 ml/min/kg, k13 increased from 0.336 to 0.654 to 1.664/h and AUC(0 to infinity) decreased from 32.8 to 7.9 to 3.1 mg/L/h, respectively. Therapeutic concentrations (greater than 0.1 microgram/ml) were maintained for 15 hours, 8 hours, and about 6 hours in 1-, 7-, and 42-day-old calves, respectively. Penetration of SDZ and TMP into the CSF in 42-day-old calves was substantial; ratios of AUC(CSF)/AUCserum were 0.60 and 0.69, respectively. Therapeutic concentrations of drugs in CSF were maintained if serum concentrations were above therapeutic concentrations; elimination rates of both drugs from the CSF equaled those of serum. Sulfadiazine was excreted mainly unchanged; the percentage of dose excreted unchanged in 24 hours increased from 22.1 to 47.8 to 50.8% in 1-, 7-, and 42-day-old calves, respectively, paralleling the increase in CLtot. Trimethoprim was extensively biotransformed; the percentage of dose excreted unchanged in the urine in 24 hours decreased from 12.8 to 8.7 to 3.5%. Sulfadiazine and TMP were concentrated in the urine, and therapeutic concentrations of both drugs in urine were maintained for greater than 24 hours in calves of all ages.
显示更多 [+] 显示较少 [-]Ivermectin plasma concentrations in Collies sensitive to ivermectin-induced toxicosis
1989
Tranquilli, W.J. | Paul, A.J. | Seward, R.L.
Five Collies sensitive to toxic effects of ivermectin and 7 nonsensitive Collies were given 100 microgram of ivermectin/kg of body weight, PO. Blood samples were collected from each dog before treatment; at posttreatment hours 1, 2, 3.5, 5, and 8; and at posttreatment days 1, 2, 4, 7, 14, and 21. Each sample was assayed for ivermectin concentration, and statistical analyses were performed on the resulting plasma concentration data to determine differences in absorption and clearance of drugs between the 2 groups. Variables measured were area under the curve (using the trapezoidal rule), peak plasma concentration, and the time to peak concentration. Differences between sensitive and nonsensitive Collies for variables analyzed were not significant (P greater than 0.05).
显示更多 [+] 显示较少 [-]Continuous electromyographic recordings of pharyngeal muscle activity in normal and previously denervated muscles in dogs
1989
Venker-van Haagen, A.J. | Hartman, W. | Brom, W.E. van den | Wolvekamp, W.Th.C.
Continous electromyographic recordings of pharyngeal muscle activity were made in 5 clinically normal control dogs and in 7 dogs 3 years after partial denervation of the pharyngeal muscles. Electromyographic recordings were made of the sequence of actions of each muscle and of the combined muscle activity, at rest and during swallowing of food. During 30-second periods, the recordings were digitalized and stored on diskette for further analysis. All control dogs had a distinct pattern of muscle activity during swallowing, the onset being in a constant order (hyopharyngeal, thyropharyngeal, and cricopharyngeal) and bilaterally synchronous. While eating, each dog had about 5 to 12 short periods of synchronous activity in each muscle, between the swallowing actions. During the resting period, there were longer periods of activity, which were synchronous with respiration. In each denervated dog, there were normal and irregular swallowing actions. Swallowing activity was recognized, but the sequence of hyopharyngeal, thyropharyngeal, and cricopharyngeal muscle activity was irregular and different from that in control dogs. Partial denervation of the pharyngeal muscles does not seriously impair motor activity of the muscles, but does alter the sequence of activity in the pharyngeal muscles during swallowing.
显示更多 [+] 显示较少 [-]Pharmacokinetics of ceftazidime given alone and in combination with probenecid to unweaned calves
1989
Soback, S. | Ziv, G.
Ceftazidime pharmacokinetic values were studied in unweaned calves given the antibiotic alone or in combination with probenecid. Ceftazidime was administered IV to 9 calves at a dosage of 10 mg/kg of body weight and IM (10 mg/kg) to 8 calves, to 7 calves (10 mg/kg plus probenecid [40 mg/kg]), and to 9 calves (10 mg/kg plus probenecid [80 mg/kg]). Serum concentration-vs-time data were analyzed, using noncompartmental methods based on statistical moment theory. The data for IV ceftazidime administration also were fitted by use of a linear, open 2-compartment model. The mean (+/- SD) terminal half-life was 138.7 +/- 23.6 minutes and 126.3 +/- 10.5 minutes after IV and IM administrations, respectively. The mean residence time was 167.3 +/- 21.1 minutes and 201.4 +/- 16.8 minutes after IV and IM administrations, respectively. Coadministration of probenecid did not affect the terminal half-life or mean residence time values. The total body clearance was 1.75 +/- 0.26 ml/min/kg, and the volume of distribution at steady state was 0.294 +/- 0.064 L/kg. The estimated mean absorption time was 34.1 minutes. There were no significant differences between the mean residence time calculated by statistical moment theory or by compartmental analysis, indicating central compartment output of ceftazidime. The 90% minimal inhibitory concentration values of ceftazidime determined for Escherichia coli, Salmonella spp, Pasteurella multocida, and P haemolytica isolates ranged from less than 0.01 to 0.1 microgram/microliter.
显示更多 [+] 显示较少 [-]In situ production of interferon in tissues of chickens exposed as embryos to turkey herpesvirus and Marek's disease virus
1989
Sharma, J.M.
Chicken eggs at embryonation day (ED) 18 or newly hatched chicks were inoculated with turkey herpesvirus (HVT), Marek's disease virus (MDV), or virus-free diluent and, at intervals after inoculation, tissue homogenates of virus-exposed and virus-free chickens or chicken embryos were examined for interferon (IFN) activity. Homogenates of lung thymus and spleen specimens from chickens given HVT at ED 18 had IFN activity. Activity of IFN in the lungs was studied further. Homogenates of lung specimens from chickens exposed to HVT at hatching also had IFN activity, although the concentration of IFN was lower than that in chickens given HVT at ED 18. The pathogenic isolates of MDV (JM-(MDV)), but not the atenuated (Md11/75C-(MDV)) or nonpathogenic (SB1-(MDV)) isolates, inoculates at ED 18 also induced high lung IFN activity. Exposure to a combination of HVT and SB1-MDV induced IFN activity comparable with that in chickens given HVT alone. The IFN activity in homogenates of lung specimens from virus-exposed chickens was species specific and heat and pH stable, but was destroyed by trypsin treatment. Occassionally, low IFN activity also was detected in homogenates of tissus specimens from virus-free chickens or chicken embryos. This IFN activity could have been produced constitutively or may have been induced by substances (inducers) in the environment.
显示更多 [+] 显示较少 [-]Effect of dry, soft moist, and canned dog foods on postprandial blood glucose and insulin concentrations in healthy dogs
1989
Holste, L.C. | Nelson, R.W. | Feldman, E.C. | Bottoms, G.D.
The effect of dry, soft moist, and canned dog foods on immediate postprandial plasma glucose and insulin concentrations was evaluated in clinically normal dogs. Dogs were fed either dry (10 dogs; group I), soft moist (10 dogs; group II), or canned (8 dogs; group III) dog food for 5 consecutive days. On the fifth day, plasma glucose and insulin concentrations were determined in each dog prior to, during, and at 5, 10, 15, 30, 45, 60, 90, 120, 180, and 240 minutes after ingestion of the food. The alterations in plasma glucose concentrations were not significantly different from prefeeding values until 240 and 180 minutes after feeding for groups I and III, respectively. In contrast, the increments in plasma glucose were significantly (P less than 0.01) increased from basal concentrations at 30 and 45 minutes after feeding in group-II dogs. The maximal mean postprandial plasma glucose concentration was significantly (P less than 0.0001) less for group III, compared with concentrations for groups I and II, but there was no significant difference between concentrations for groups I and II. Although a bisphasic insulin secretory response was found in all 3 groups of dogs, the patterns of phase-2 insulin secretion and the total amount of insulin secreted during the study were significantly different. There was a rapid increase in the plasma insulin concentration immediately after phase 1 in group II, with maximal plasma insulin concentrations occurring 30 minutes after feeding, followed by a gradual decrease in concentrations throughout the remainder of the study. In contrast, plasma insulin concentrations increased steadily in groups I and III, after phase-1 insulin secretion, with maximal values occurring at 240 minutes after feeding. The maximal mean increase from basal insulin concentrations during phase-2 secretion was significantly (P less than 0.005) greater for group II (80 +/- 15 micro IU/ml) than for groups I and III (23 +/- 3 and 24 +/- 6 micro IU/ml, respectively). Whereas the integrated areas under the glucose response curves were not significantly different between groups, total insulin secretion and total insulin secreted during phases 1 and 2 were significantly (P less than 0.01) greater in group II than in groups I and III. Differences in dietary composition may offer the best explanation for differences in postprandial glucose concentrations and insulin secretory responses between groups. These findings emphasize the importance of dietary formulations when designing hormonal studies or interpreting research data when dogs are the animal model.
显示更多 [+] 显示较少 [-]Identification of a virulence factor for Brucella abortus infection in BALB/c mice
1989
Pugh, G.W. Jr | Tabatabai, L.B. | Bricker, B.J. | Mayfield, J.E. | Phillips, M. | McDonald, T.J. | Zehr, E.S.
Immunogenic or pathogenic factors of recombinant proteins (rBCSP20, rBCSP-31, and rBCSP45 of Brucella abortus strain 19) for mice were compared with factors of a proteinase K-treated lipopolysaccharide extracted from B abortus strain 2308. Mice were vaccinated with 4 products, using different inoculation schedules and were challenge exposed with a virulent culture of B abortus strain 2308. Blood samples were collected 2 weeks after vaccination and at necrospy and sera were obtained. Spleens were cultured for B abortus at necropsy (3 to 4 weeks after challenge exposure). Mice given proteinase K-treated lipopolysaccharide alone or in conjunction with rBCSP20 or rBCSP45 proteins were protected, but mice given rBCSP31 on the same day as challenge exposure were not. Vaccination with recombinant proteins alone neither provide protection nor significantly (P greater than 0.05) increase the pathogenic effect of the challenge-exposure culture. Seemingly, rBCSP31 might be a virulence factor of B abortus.
显示更多 [+] 显示较少 [-]Serodiagnosis of ovine paratuberculosis, using lipoarabinomannan in an enzyme-linked immunosorbent assay
1989
Sugden, E.A. | Corner, A.H. | Samagh, B.S. | Brooks, B.W. | Turcotte, C. | Nielsen, K.H. | Stewart, R.B. | Duncan, J.R.
The use of lipoarabinomannan (LAM; obtained from Mycobacterium paratuberculosis) in an ELISA (LAM-ELISA) to test 75 sheep sera from a paratuberculosis-infected flock resulted in an approximate threefold increase in sensitivity (from 23.5% to 70.6%), compared with the use of Annau's polysaccharide in a complement fixation test (P-CFT). Even after manipulation of the LAM-ELISA cut-off value to produce a specificity of 100% to match that of the P-CFT, the sensitivity still was approximately twofold greater than that of the P-CFT. Anti-bovine monoclonal antiglobulin-enzyme conjugates matched commercially available anti-ovine polyclonal antiglobulin-enzyme conjugates with respect to sensitivity and specificity. False-positive results were found to be less frequent after combining 2 serodiagnostic tests, LAM-ELISA and D antigenagar gel immunodiffusion, resulting in an increase in specificity from 88.1% to 95.2%. The repeatability of true seropositive and seronegative results was found to be 89.5% and 91.1%, respectively, for sera obtained less than or equal to 1 month prior to slaughter and 91.7% and 95.5%, respectively, for reanalysis of sera obtained at the time of slaughter.
显示更多 [+] 显示较少 [-]Turbinate perimeter ratio as an indicator of conchal atrophy for diagnosis of atrophic rhinitis in pigs
1989
Collins, M.T. | Backstrom, L.R. | Brim, T.A.
Transverse sections of snouts from 171 cross-bred (principally Yorkshire X American Landrace) pigs were evaluated for evidence of turbinate atrophy by use of conventional (atrophic rhinitis [AR] score) and morphometric methods. Of the 171 pigs, 35 were clinically normal (AR score, 0), 65 had mild AR (AR score, 1), 41 had moderate AR (AR score, 2), and 30 had severe AR (AR score, 3). Turbinate cross-sectional area (TA) and the ratio of TA to nostril cross-sectional area, called turbinate area ratio (TAR), had the lowest correlations (r = 0.24 to 0.55) with conventional AR score. Among clinically normal pigs, TA was greater in older pigs as expected, but the TAR values also were significantly (P less than 0.0001) different betwee n 15-week-old pigs (55 kg) and 22-week-old pigs (100 kg). Turbinate perimeter and turbinate perimeter ratio (TPR) were not influenced by pig age or source. The TPR values were closely correlated with subjective visual AR scores (r = 0.73), with AR scores derived by measuring the space between the ventral portion of the scroll and the floor of the nasal cavity (r = 0.72), and the actual size of this space in millimeters (r = 0.71). Mean TPR values for pigs assigned visual AR scores of 0, 1, 2, or 3 were 1.54, 1.25, 0.97, and 0.73, respectively. The 95% confidence intervals around these mean TRP values were discreet and did not overlap. Turbinate perimeter ratio, therefore, may be a more reliable morphometric measure of atrophic rhinitis and also provides parametric data suitable for quantitative analysis.
显示更多 [+] 显示较少 [-]Sites of virus replication in the genital organs of boars inoculated in the cavum vaginale with pseudorabies virus
1989
Miry, C. | Pensaert, M.B.
To determine the sites of replication and the evolution of pseudorabies virus infection in boar genital organs, 5 Belgian Landrace boars were inoculated with pseudorabies virus unilaterally in the cavum vaginale of the testis. Virus replication took place only in cells of the tunica vaginalis of both cava vaginalia. Infection of the serosa led to exudative periorchitis and increased scrotal fluid, resulting in a severely swollen scrotal region. These experimental findings were similar to findings in boars with naturally aquired pseudorabies virus infection. Scrotal fluid contained large amounts of virus, making it a useful specimen for diagnosis of the disease in affected boars.
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