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In vitro effect of pimobendan on platelet aggregation in dogs
2013
Shipley, Eryn A. | Hogan, Daniel F. | Fiakpui, Nonya N. | Magee, Aliya N. | Green, Henry W III | Sederquist, Kimberly A.
Objective: To determine whether pimobendan has in vitro antithrombotic properties through inhibition of platelets in canine blood samples. Animals: 10 healthy adult dogs. Procedures: Blood samples were collected from each dog into tubes containing hirudin or sodium citrate. Pimobendan was added to blood samples (final concentration, 0.0, 0.01, 0.1, 1.0, or 10.0μM) containing hirudin prior to undergoing collagen- and ADP-induced whole blood impedance aggregometry. Plasma thromboxane concentrations were measured after platelet aggregation. Pimobendan was also added to blood samples (0.0, 0.01, or 10.0μM) containing sodium citrate prior to thromboelastographic evaluation. Results: Compared with findings for 0.0μM pimobendan, composite platelet aggregation (area under the curve [AUC]) and maximal platelet aggregation (aggregation units [AUs]) at 10.0μM pimobendan were significantly decreased for collagen-induced aggregation (AUC, 349.7 ± 58.4 vs 285.1 ± 72.2; maximal platelet aggregation, 196.2 ± 25.8 AUs vs 161.5 ± 38.0 AUs), and the AUC and velocity of aggregation at 10.0μM pimobendan were significantly decreased for ADP-induced aggregation (AUC, 268.5 ± 35.1 vs 213.4 ± 77.2; velocity of aggregation, 15.7 ± 2.9 AUs/min vs 11.8 ± 3.5 AUs/min). Pimobendan had no significant effect on plasma thromboxane concentration or thromboelastographic variables, regardless of concentration. Conclusions and Clinical Relevance: In vitro, pimobendan had an antiplatelet effect in canine blood samples at a concentration 1,000-fold higher than that clinically achievable. These antiplatelet properties do not appear to contribute to the positive clinical profile of the drug in dogs. Pimobendan administration would not appear to confer a risk for bleeding and does not have to be avoided in dogs with thrombocytopenia or those concurrently receiving antiplatelet drugs.
Mostrar más [+] Menos [-]Evaluation of mass spectrometry of urinary proteins and peptides as biomarkers for cats at risk of developing azotemia
2013
Jepson, Rosanne E. | Coulton, G. R. (Gary R) | Cowan, Matthew L. | Markwell, Peter | Syme, Harriet M. | Elliott, Jonathan
Objective: To evaluate proteomic delineation of feline urine by mass spectrometry as a method for identifying biomarkers in cats at risk of developing azotemia. Samples: Urine samples from geriatric cats (> 9 years old) with chronic kidney disease and nonazotemic cats that either remained nonazotemic (n = 10) or developed azotemia (10) within 1 year. Procedures: Optimization studies with pooled urine were performed to facilitate the use of surface enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) for analysis of the urinary proteome of cats. Urine samples from nonazotemic cats at entry to the study were analyzed via SELDI-TOF-MS with weak cation exchange and strong anion exchange arrays. Spectral data were compared to identify biomarkers for development of azotemia. Results: Low protein concentration in feline urine precluded direct application to array surfaces, and a buffer exchange and concentration step was required prior to SELDI-TOF-MS analysis. Three preparation conditions by use of weak cation and strong anion exchange arrays were selected on the basis of optimization studies for detection of biomarkers. Eight potential biomarkers with an m/z of 2,822, 9,886, 10,033, 10,151, 10,234, 11,653, 4,421, and 9,505 were delineated. Conclusions and Clinical Relevance: SELDI-TOF-MS can be used to detect urinary low-molecular weight peptides and proteins that may represent biomarkers for early detection of renal damage. Further study is required to purify and identify potential biomarkers before their use in a clinical setting.
Mostrar más [+] Menos [-]Association of perinatal exposure to airborne Rhodococcus equi with risk of pneumonia caused by R equi in foals
2013
Cohen, Noah D. | Chaffin, M Keith | Kuskie, Kyle R. | Syndergaard, Melissa K. | Blodgett, Glenn P. | Takai, Shinji
Objective: To determine whether the concentrations of airborne virulent Rhodococcus equi in stalls housing foals during the first 2 weeks after birth are associated with subsequent development of R equi pneumonia in those foals. Sample: Air samples collected from foaling stalls and holding pens in which foals were housed during the first 2 weeks after birth. Procedures: At a breeding farm in Texas, air samples (500 L each) were collected (January through May 2011) from stalls and pens in which 121 foals were housed on day 1 and on days 4, 7, and 14 after birth. For each sample, the concentration of airborne virulent R equi was determined with an immunoblot technique. The association between development of pneumonia and airborne R equi concentration was evaluated via random-effects Poisson regression analysis. Results: Some air samples were not available for analysis. Of the 471 air samples collected from stalls that housed 121 foals, 90 (19%) contained virulent R equi. Twenty-four of 121 (20%) foals developed R equi pneumonia. Concentrations of virulent R equi in air samples from stalls housing foals that developed R equi pneumonia were significantly higher than those in samples from stalls housing foals that did not develop pneumonia. Accounting for disease effects, air sample concentrations of virulent R equi did not differ significantly by day after birth or by month of birth. Conclusions and Clinical Relevance: Exposure of foals to airborne virulent R equi during the first 2 weeks after birth was significantly (and likely causally) associated with development of R equi pneumonia.
Mostrar más [+] Menos [-]Field study of the comparative efficacy of gamithromycin and tulathromycin for the control of undifferentiated bovine respiratory disease complex in beef feedlot calves at high risk of developing respiratory tract disease
2013
Torres, Siddartha | Thomson, Dan U. | Bello, Nora M. | Nosky, Bruce J. | Reinhardt, Chris D.
Objective-To compare the efficacy of gamithromycin with that of tulathromycin for control of undifferentiated bovine respiratory disease complex (BRDC) in feedlot calves. Animals-2,529 weaned crossbred beef calves. Procedures-At each of 2 feedlots, calves at risk of developing BRDC were administered a single dose of gamithromycin (6.0 mg/kg, SC; n = 1,263) or tulathromycin (2.5 mg/kg, SC; 1,266) metaphylactically. Health (BRDC morbidity, mortality, case-fatality, and retreatment rates) and performance (average daily gain, dry matter intake, and feed-to-gain ratio) outcomes were compared between treatments via classical hypothesis testing. Bioequivalence limits for gamithromycin and tulathromycin were established for outcomes for which no significant difference between treatments was detected. Results-Mean BRDC morbidity rate (31.0%) for calves administered gamithromycin was greater than that (22.9%) for calves administered tulathromycin; otherwise, health and performance did not differ between treatments. Limits for mean differences within which gamithromycin was considered bioequivalent to tulathromycin were +/- 10% for BRDC retreatment rate, +/- 3.5% for BRDC mortality rate, ± 16% for case-fatality rate, +/- 37 kg for final body weight, +/- 0.1 kg/d for average daily gain, +/- 0.3 kg/d for dry matter intake, and +/- 0.7 for feed-to-gain ratio. Conclusions and Clinical Relevance-The efficacy of gamithromycin did not differ from that of tulathromycin for all outcomes except morbidity rate; calves administered gamithromycin had a higher BRDC morbidity rate than did calves administered tulathromycin. On the basis of the bioequivalence limits established for this dataset, gamithromycin was considered equivalent to tulathromycin for the control of BRDC.
Mostrar más [+] Menos [-]Short-term effect of ovariectomy on measures of insulin sensitivity and response to dexamethasone administration in horses
2013
Bertin, François R. | Pader, Karine S. | Lescun, Timothy B. | Sojka-Kritchevsky, Janice E.
Objective—To evaluate the effect of ovariectomy on insulin sensitivity in horses and determine whether the effects of suppression of the hypothalamo-pituitary-adrenal axis differ before and after ovariectomy. Animals—6 healthy mares. Procedures—The horses underwent an IV glucose tolerance test (IVGTT), an insulin sensitivity test, and a dexamethasone suppression test before and 5 weeks after ovariectomy. Body weight, serum cortisol and plasma ACTH concentrations, serum insulin-to-blood glucose concentration ratios, and changes in blood glucose concentration with time after injection of glucose or insulin were compared before and after ovariectomy. Results—The dexamethasone injection resulted in a decrease in serum cortisol concentration before and after ovariectomy. In all horses, baseline plasma ACTH concentrations were within the reference range before and after ovariectomy. For each mare, results of an IVGTT before and after ovariectomy were considered normal. No significant differences in basal blood glucose concentration or time to reach baseline glucose concentration after an IVGTT were observed. Basal serum insulin concentration and serum insulin-to-blood glucose concentration ratios were not significantly different before or after ovariectomy, nor was the mean time to attain a 50% decrease in blood glucose concentration after insulin injection. Conclusions and Clinical Relevance—Results indicated that ovariectomy does not appear to modify dexamethasone response in horses and that it does not modify short-term measures of insulin sensitivity. Findings suggested that horses undergoing ovariectomy are not at higher risk of developing equine metabolic syndrome or hypothalamo-pituitary-adrenal axis dysfunction and associated morbidity.
Mostrar más [+] Menos [-]Effects of inspired oxygen concentration on ventilation, ventilatory rhythm, and gas exchange in isoflurane-anesthetized horses
2013
Crumley, Mariana N. | McMurphy, Rose M. | Hodgson, David S. | Kreider, Scott E.
Objective: To compare the effects of 2 fractions of inspired oxygen, 50% and > 95%, on ventilation, ventilatory rhythm, and gas exchange in isoflurane-anesthetized horses. Animals: 8 healthy adult horses. Procedures: In a crossover study design, horses were assigned to undergo each of 2 anesthetic sessions in random order, with 1 week separating the sessions. In each session, horses were sedated with xylazine hydrochloride (1.0 mg/kg, IV) and anesthesia was induced via IV administration of diazepam (0.05 mg/kg) and ketamine (2.2 mg/kg) Anesthesia was subsequently maintained with isoflurane in 50% or > 95% oxygen for 90 minutes. Measurements obtained during anesthesia included inspiratory and expiratory peak flow and duration, tidal volume, respiratory frequency, end-tidal CO2 concentration, mixed expired partial pressures of CO2 and O2, Pao2, Paco2, blood pH, arterial O2 saturation, heart rate, and arterial blood pressure. Calculated values included the alveolar partial pressure of oxygen, alveolar-to-arterial oxygen tension gradient (Pao2 − Pco2), rate of change of Pao2 − Pao2, and physiologic dead space ratio. Ventilatory rhythm, based on respiratory rate and duration of apnea, was continuously observed and recorded. Results: Use of the lower inspired oxygen fraction of 50% resulted in a lower arterial oxygen saturation and Pao2 than did use of the higher fraction. No significant difference in Paco2, rate of change of Pao2 − Pao2, ventilatory rhythm, or other measured variables was observed between the 2 sessions. Conclusion and Clinical Relevance: Use of 50% inspired oxygen did not improve the ventilatory rhythm or gas exchange and increased the risk of hypoxemia in spontaneously breathing horses during isoflurane anesthesia. Use of both inspired oxygen fractions requires adequate monitoring and the capacity for mechanical ventilation.
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