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- Author or Editor: Raymond W. Sweeney x
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Abstract
Objective—To determine the pharmacokinetics and pharmacodynamics of ϵ-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses.
Animals—6 adult horses.
Procedures—Each horse received 3.5 mg of EACA/kg/min for 20 minutes, IV. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma α2-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration versus time data were evaluated by use of a pharmacokinetic analysis computer program.
Results—Drug disposition was best described by a 2-compartment model with a rapid distribution phase, an elimination half-life of 2.3 hours, and mean residence time of 2.5 ± 0.5 hours. Peak plasma EACA concentration was 462.9 ± 70.1 μg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 μg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma α2-antiplasmin activity at 1 or 4 hours after infusion. Thirty minutes after infusion, platelet function was significantly different from that at time 0 and 1 and 4 hours after infusion. The continuous rate infusion that would maintain proposed therapeutic plasma concentrations of EACA was predicted (ie, 3.5 mg/kg/min for 15 minutes, then 0.25 mg/kg/min).
Conclusions and Clinical Relevance—Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.
Abstract
OBJECTIVE To determine serum and tissue concentrations of gallium (Ga) after oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to neonatal calves.
ANIMALS 8 healthy neonatal calves.
PROCEDURES Calves were assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24 hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after Ga administration on day 5. On day 6, calves were euthanized and tissue samples were obtained. Serum and tissue Ga concentrations were measured by use of mass spectrometry.
RESULTS Data were adjusted for total Ga dose, and comparisons were made between the 2 groups. Calves receiving GaM had a significantly higher dose-adjusted area under the curve and dose-adjusted maximum serum Ga concentration than did calves receiving GaN. Despite receiving less Ga per dose, calves receiving GaM had tissue Ga concentrations similar to those for calves receiving GaN.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, calves receiving GaM had significantly higher Ga absorption than did calves receiving GaN. These findings suggested that GaM might be useful as a prophylactic agent against Mycobacterium avium subsp paratuberculosis infection in neonatal calves. (Am J Vet Res 2016;77:151–155)
Abstract
Objective—To evaluate the in vitro susceptibility of various field isolates of Mycobacterium avium subsp paratuberculosis (MAP) to gallium nitrate.
Sample—10 isolates of MAP, including 4 isolated from cattle, 2 isolated from bison, 1 isolated from an alpaca, and 3 isolated from humans.
Procedures—The in vitro susceptibility to gallium nitrate was tested by use of broth culture with detection of MAP growth by means of a nonradiometric automated detection method. For each MAP isolate, a series of 7 dilutions of gallium nitrate (concentrations ranging from 200 to 1,000μM) were tested. Gallium nitrate was considered to have caused 90% and 99% inhibition of the MAP growth when the time to detection for culture of the MAP stock solution and a specific concentration of gallium nitrate was delayed and was similar to that obtained for culture of the MAP stock solution (without the addition of gallium nitrate) diluted 1:10 and 1:100, respectively.
Results—Gallium nitrate inhibited MAP growth in all 10 isolates. The susceptibility to gallium nitrate was variable among isolates, and all isolates of MAP were inhibited in a dose-dependent manner. Overall, the concentration that resulted in 90% inhibition ranged from < 200μM for the most susceptible isolates to 743μM for the least susceptible isolates.
Conclusions and Clinical Relevance—Gallium nitrate had activity against all 10 isolates of MAP tested in vitro and could potentially be used as a prophylactic agent to aid in the control of MAP infections during the neonatal period.
Abstract
Objective—To evaluate the effect of vaccination of calves with a killed Mycobacterium avium subsp paratuberculosis (MAP) vaccine on colonization of tissues following oral MAP exposure.
Animals—12 healthy Holstein calves.
Procedures—At 14 days after birth, calves received the MAP vaccine (1.0 mL, SC) or saline (0.9% NaCl) solution (1.0 mL, SC [control treatment]). Each calf received 1.2 × 109 CFUs of live MAP orally 21 and 22 days after vaccination. Prior to vaccination and at subsequent intervals, a blood sample was collected for ELISA detection of antibodies against MAP and for whole blood, antigen-specific, interferon (IFN)-γ–release assay. Nine weeks after MAP challenge, calves were euthanized and various tissue samples were collected for mycobacterial culture. Interferon-γ production in prescapular lymph node cells was measured following in vitro stimulation with MAP antigens.
Results—Calves were seronegative for anti-MAP antibodies at all times. Compared with the findings in control calves, antigen-specific IFN-γ production in circulating lymphocytes and prescapular lymph node cells from vaccinated calves was significantly higher. Culture of tissues from vaccinated calves yielded significantly fewer CFUs of MAP (2,417 CFUs/g), compared with tissues from control calves (15,709 CFUs/g). Furthermore, significantly fewer tissue samples from vaccinated calves yielded MAP in culture (21.8 tissues/calf), compared with findings in control calves (27.6 tissues/calf).
Conclusions and Clinical Relevance—Inoculation of calves with a killed MAP vaccine was associated with reduced colonization of intestinal tissues following experimental exposure to MAP. Use of the vaccine could potentially reduce transmission of MAP to calves in infected herds.
Abstract
Objective—To evaluate sensitivity and specificity of a new ELISA for antibodies against Mycobacterium avium subsp paratuberculosis.
Design—Cross-sectional observational survey.
Sample Population—Serum samples from 590 cattle that were infected with M avium subsp paratuberculosis and 723 cattle that were not infected.
Procedure—Serum samples were tested by use of an ELISA for antibodies against M avium subsp paratuberculosis.
Results—Sensitivity of the test varied from 15.4 to 88.1%, depending on the clinical stage and bacterial shedding status of the cattle.
Conclusions and Clinical Relevance—Results obtained with use of the new ELISA agreed favorably with those of a previous ELISA. Practitioners must be aware of variability in the sensitivity of the test, which depends on the clinical and shedding status of the cattle, because this may affect interpretation of test results. (J Am Vet Med Assoc 2001;218:1163–1166)
