Pharmacokinetics of oral tapentadol in cats.

To evaluate pharmacokinetics of one dose of tapentadol hydrochloride orally administered to cats. Prospective experimental study. Five healthy adult mixed-breed cats. Each cat received 18.8 ± 1.0 mg/kg tapentadol orally. Venous blood samples were collected at time 0 (immediately prior to administration of tapentadol) 1, 2, 5, 10, 15, 30, 45, 60, 90 min, and 2, 4, 8, 12 to 24 h after drug administration. Plasma tapentadol concentrations and its metabolites were determined using ultra-performance liquid chromatography-tandem mass spectrometry. Geometric mean Tmax of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.3, 7.0, 6.0, and 4.6 h, respectively. Mean Cmax of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 637, 66, 1134, and 15,757 ng/mL, respectively, after administration. Mean half-life of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.4, 4.7, 2.9, and 10.8 h. The relative exposure of tapentadol and its metabolites were tapentadol 2.65%, desmethyltapentadol 0.54%, tapentadol-O-glucuronide 6.22%, and tapentadol-O-sulfate 90.6%. Tapentadol-O-sulfate was the predominant metabolite following the administration of oral tapentadol in cats. Further studies are warranted to evaluate the association of analgesia with plasma concentrations of tapentadol.

Effect of timing of prepartum vaccination relative to pen change with an acidogenic diet on lying time and metabolic profile in Holstein dairy cows.

The objective was to assess the effect of prepartum vaccination timing relative to pen change with an acidogenic diet at 28 or 21 d before expected parturition (dpp) on lying time (LT), prepartum serum energy status (glucose, IGF-1, and nonesterified fatty acids), urine pH, and serum Ca at calving in pregnant Holstein dairy cows. Pregnant multiparous Holstein cows (n = 308) from 1 large dairy herd were randomly allocated into 1 of 3 treatment groups at 35 ± 3 dpp as follows: (1) vaccination at 28 dpp and pen change at 21 dpp (V28PC21; n = 108), (2) vaccination and pen change at 28 dpp (V28PC28; n = 99), and (3) vaccination and pen change at 21 dpp (V21PC21; n = 101). When cows changed pens, an acidogenic diet was introduced. Every other week, a group of 43 to 53 animals were enrolled and electronic data loggers (IceQube, IceRobotics) were fitted to the hind leg of individual cows to assess their LT. Blood samples were collected at 28, 26, 21, 19, 14 dpp and at calving. Parity, body condition score, days dry, and gestation length were not different among groups. Overall, V28PC28 cows had 7 additional days in prepartum pens consuming an acidogenic diet compared with V28PC21 or V21PC21 cows. Regardless of treatment group, cows in the far-off pen had 43 min/d less LT (709 vs. 753 min/d) and increased day-to-day coefficient of variation of LT (0.21 vs. 0.10) compared with cows within the prepartum pen. On average, for the 7 d following vaccination alone (28 to 22 dpp period), V28PC21 cows had ~22 min/d less LT compared with V21PC21 cows. Serum concentrations of glucose, nonesterified fatty acids, and IGF-1 were altered following vaccination alone, pen change alone, or vaccination plus pen change with an acidogenic diet before calving. At calving, V28PC21 cows had greater glucose concentrations (6.45 mmol/L) compared with V21PC21 cows (5.76 mmol/L), with V28PC28 cows intermediate (6.11 mmol/L). The assessment of Ca status at calving revealed that V28PC21 cows had greater Ca concentration (2.34 mmol/L) with lower subclinical hypocalcemia (<2.0 mmol/L; 17.3%) compared with V21PC21 cows (2.17 mmol/L and 31.9%), with V28PC28 cows intermediate (2.28 mmol/L and 25.2%). Serum concentrations of IGF-1 at calving were also greater for V28PC21 (3.43 nmol/L) cows compared with V21PC21 (2.69 nmol/L), with V28PC28 cows intermediate (3.07 nmol/L). Overall, V28PC21 cows had greater serum glucose, IGF-1, and ~46% reduction in subclinical hypocalcemia (from 31.9 to 17.3%) compared with V21PC21 cows but did not differ from V28PC28 cows (25.2%). These findings provided evidence that vaccinating cows at 28 dpp, followed 7 d later by pen change with an acidogenic diet at 21 dpp, would be beneficial.

Effects of prepartum vaccination timing relative to pen change with an acidogenic diet on serum and colostrum immunoglobulins in Holstein dairy cows.

The objective of the present study was to assess the effects of prepartum vaccination timing relative to pen change with an acidogenic diet at 28 or 21 d before expected parturition (dpp) on colostral and serum IgG concentrations at calving in pregnant Holstein dairy cows. Pregnant multiparous Holstein cows (n = 308) from one large dairy herd were randomly allocated into 1 of 3 treatment groups at 35 ± 3 dpp: (1) vaccination at 28 dpp and pen change at 21 dpp (V28PC21; n = 108), (2) vaccination and pen change at 28 dpp (V28PC28; n = 99), and (3) vaccination and pen change at 21 dpp (V21PC21; n = 101). An acidogenic diet was fed when cows changed pens at 28 or 21 dpp. Blood and colostral samples were collected within 1 h following parturition. The total number of clinical mastitis (CM) cases within the first 150 d in milk (DIM) were recorded. The V28PC21 cows had greater colostral IgG concentrations at calving (160.4 ± 7.0 g/L) compared with V21PC21 cows (134.4 ± 7.0 g/L), and V28PC28 cows were intermediate (148.3 ± 7.2 g/L). At calving, V28PC21 cows had lower serum IgG concentrations (29.1 ± 1.2 g/L) compared with V21PC21 cows (32.2 ± 1.2 g/L) or V28PC28 cows (32.6 ± 1.3 g/L). Overall, 41% of V21PC21 cows received the booster vaccinations with at least 21 d before actual calving compared with V28PC21 or V28PC28 cows (88 and 86% respectively). The shorter the interval from prepartum booster vaccination to calving, the lower the colostral IgG at calving, regardless of treatment groups. Vaccinating at 28 dpp and pen change with an acidogenic diet at 21 dpp tended to reduce the rate of CM within the first 150 DIM compared with V21PC21. These findings provide evidence that vaccinating cows at 28 dpp, followed by pen change with an acidogenic diet at 21 dpp, improved the concentrations of colostral IgG at calving and tended to reduce the rate of CM. The interaction of prepartum vaccination timing relative to feeding an acidogenic diet should be considered when implementing an effective vaccination program to enhance overall herd health.

Administration of acetylsalicylic acid after parturition in lactating dairy cows under certified organic management: Part II. Biomarkers of nociception, inflammation, and stress.

The objective was to assess the effect of oral administration of acetylsalicylic acid after calving on the concentrations of substance P (SP), haptoglobin (HP), and cortisol in lactating dairy cows. Holstein dairy cows (n = 152) from 3 organic herds were included. At parturition, cows were blocked by parity [multiparous (MULT) and primiparous (PRIM)] and calving ease [eutocia (EUT) and dystocia (DYS)] and were randomly assigned to 1 of 2 treatment groups: aspirin (ASP; n = 76), in which within 12 h after parturition cows received 4 treatments with acetylsalicylic acid (100 mg/kg; 2 boluses) at 12-h intervals, or placebo (PLC; n = 76), in which within 12 h after parturition cows received 4 consecutive treatments with gelatin capsules (2 capsules) containing water 12 h apart. Blood samples were collected immediately before treatment and at 12, 24, 36, 48, and 168 h (7 DIM) for assessment of circulating concentration of SP, HP, and cortisol. Based on farm records, cows were classified in the following clinical disease categories: no clinical disease event (NO-EVT), a single clinical disease event (SI-EVT), and more than 1 clinical disease event (MU-EVT). The study data were analyzed as a randomized complete block design using mixed multiple linear and logistic regression models. With regard to HP, there was a tendency for an interaction between treatment and parity, where MULT cows treated with ASP had lower concentration of HP compared with MULT cows treated with PLC (ASP = 124.33 ± 6.83 µg/mL; PLC = 143.9 ± 7.24 µg/mL). Analysis by calving ease showed that cows with DYS had higher concentrations of HP (DYS = 159.17 ± 5.97 µg/mL; EUT = 138.72 ± 6.22 µg/mL) and SP (only at 168 h; DYS = 64.99 pg/mL, 95% confidence interval, CI: 2.68-2.81; EUT = 60.33 pg/mL, 95% CI: 2.91-3.06) after calving compared with EUT cows. Regardless of treatment, PRIM cows had higher concentrations of SP (MULT = 55.11 pg/mL, 95% CI: 1.27-1.30; PRIM = 57.62 pg/mL, 95% CI: 1.99-2.06), HP (MULT = 134.14 ± 4.96 µg/mL; PRIM = 163.75 ± 7.76 µg/mL), and cortisol (MULT = 18.65 µg/mL, 95% CI: 1.02-1.05; PRIM = 21.92 µg/mL, 95% CI: 1.67-1.74) compared with MULT cows. In addition, cows that experienced SI-EVT or MU-EVT had higher concentrations of HP (NO-EVT = 134.13 ± 5.95 µg/mL; SI-EVT = 142.68 ± 7.32 µg/mL; MU-EVT = 170.03 ± 9.42 µg/mL) and cortisol (NO-EVT = 17.86 µg/mL, 95% CI: 1.20-1.24; SI-EVT = 21.01 µg/mL, 95% CI: 1.61-1.67; MU-EVT = 22.01 µg/mL, 95% CI: 2.08-2.18) compared with cows with NO-EVT recorded. Results from this study suggest that a short-duration anti-inflammatory therapy after calving reduced HP in MULT cows but may not have effects on SP and cortisol concentrations. Calving ease and parity affected the concentrations of markers of inflammation, nociception, and stress regardless of treatment. Further research is warranted to assess anti-inflammatory strategies aimed at decreasing inflammation and stress in DYS and PRIM cows and therefore improve welfare and performance of these high-priority groups.

Effects of postpartum acetylsalicylic acid on metabolic status, health, and production in lactating dairy cattle.

The transition period is one of the most challenging times for dairy cattle. Previous research suggests that treatment of postpartum cows with anti-inflammatory drugs may decrease pain and inflammation, enhancing cow welfare and performance during this challenging period. However, these strategies involve numerous time-consuming interventions, which require extra labor and do not fit modern farm logistics. The objective of this experiment was to assess the effects of acetylsalicylic acid (ASA) every 24 h for 2 d after calving on (1) daily milk yield, daily milk conductivity, and daily rumination during the first 60 days in milk (DIM), and 305-d mature-equivalent milk, milk fat, and milk protein yields, (2) body condition score, ß-hydroxybutyrate (BHB), and haptoglobin, and (3) incidence of clinical diseases during the first 60 DIM. Dairy cows (n = 246) from a dairy farm located in Pennsylvania were enrolled in this experiment. Cows were blocked by parity and assigned randomly to 1 of 2 treatments: (1) ASA (n = 121), in which cows received 2 treatments with ASA (200 mg/kg; 4 boluses), the first within 12 h after parturition and the second 24 h later; or (2) untreated (UNT; n = 125), in which cows remained untreated. Blood samples were collected at 30 ± 6 h, 7 ± 3 d, and 14 ± 3 d after calving to measure BHB and haptoglobin concentrations. Body condition score was assessed at enrollment, 7 ± 3 DIM, 14 ± 3 DIM, and 50 ± 10 DIM. Furthermore, incidences of diseases, daily rumination, daily milk yield, and daily milk conductivity during the first 60 DIM and 305-d mature-equivalent milk, milk fat, and milk protein yields were collected from on-farm computer records. The data were analyzed using mixed multiple linear and logistic regression models as a randomized complete block design. Multiparous cows treated with ASA produced 1.64 kg/d more milk compared with multiparous cows that remained untreated (ASA = 41.66 ± 0.88 kg/d; UNT = 40.02 ± 0.81 kg/d) during the first 60 DIM. There was no difference in daily milk conductivity and rumination between treatments. Cows treated with ASA had lower concentration of BHB (ASA = 1.16 ± 0.64 mmol/L; UNT = 1.23 ± 0.80 mmol/L) during the first 14 ± 3 DIM and had higher body condition score within the first 50 ± 10 DIM compared with cows that remained UNT. There were no differences in circulating concentrations of haptoglobin between treatments. These results support previous findings showing that the use of anti-inflammatory drugs after calving may increase milk production and affect the metabolic status of dairy cows.

Short communication: Assessment of biomarkers of inflammation in the vaginal discharge of postpartum dairy cows diagnosed with clinical metritis.

Clinical metritis, characterized by the presence of an enlarged uterus and abnormal red-brownish foul-smelling vaginal discharge (VD), is a prevalent condition that causes important economic losses to dairy operations. The accurate diagnosis and treatment of this disease can help decrease its negative effects on the well-being and performance of dairy cows. The objectives of this study were to assess (1) the concentration of haptoglobin (Hp) and neutrophil-derived haptoglobin-matrix metalloproteinase 9 (Hp-MMP 9) in the VD of postpartum cows; and (2) the correlation between Hp and Hp-MMP 9 concentrations in serum and VD. Fifty-three dairy cows from 4 farms in central Pennsylvania were enrolled in this observational study.. Postpartum cows (7 ± 3 DIM) were screened using a Metricheck device to assess VD score (VDS): 1, clear fluid (n = 4); 2, < 50% white purulent fluid (n = 14); 3, > 50% white purulent fluid (n = 8); 4, red-brownish watery fluid without fetid smell (n = 22); and 5, fetid red-brownish watery fluid (n = 5). Blood and VD samples were collected for assessment of Hp and Hp-MMP 9 concentrations. Cows with a VDS of 4 or 5 (VDS4/5) had higher serum Hp concentrations than cows with a VDS of 1, 2, or 3 (VDS1/3; 93 ± 187 µg/mL vs. 59 ± 106 µg/mL, respectively). Similarly, cows with VDS4/5 had higher VD Hp concentrations than cows with VDS1/3 (73 ± 56 µg/mL vs. 17 ± 16 µg/mL, respectively). We found a significant correlation (0.37) between Hp levels in serum and in VD. We found no difference in serum Hp-MMP 9 between VDS4/5 and VDS1/3 cows. The VD concentrations of Hp-MMP 9 were higher in VDS4/5 cows than in VDS1/3 cows (7,629 ± 9,847 ng/mL vs. 1,567 ± 2,165 ng/mL, respectively). The correlation between Hp-MMP 9 in serum and VD was 0.22; nevertheless, it was not statistically significant. Interestingly, Hp and Hp-MMP 9 concentrations were higher in VD samples than in serum, regardless of VDS. Results from this study suggest that inflammatory biomarkers may be increased in cows with a VDS of 4 or 5. Further research should be aimed at elucidating the processes involved in inflammatory biomarker production and transportation in the uterus, as well as the effect of these biomarkers on endometrial cells.

Potential roles of nitrate and live yeast culture in suppressing methane emission and influencing ruminal fermentation, digestibility, and milk production in lactating Jersey cows.

Concern over the carbon footprint of the dairy industry has led to various dietary approaches to mitigate enteric CH4 production. One approach is feeding the electron acceptor NO3-, thus outcompeting methanogens for aqueous H2. We hypothesized that a live yeast culture (LYC; Saccharomyces cerevisiae from Yea-Sacc 1026, Alltech Inc., Nicholasville, KY) would stimulate the complete reduction of NO3- to NH3 by selenomonads, thus decreasing the quantity of CH4 emissions per unit of energy-corrected milk production while decreasing blood methemoglobin concentration resulting from the absorbed intermediate, NO2-. Twelve lactating Jersey cows (8 multiparous and noncannulated; 4 primiparous and ruminally cannulated) were used in a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Cattle were fed diets containing 1.5% NO3- (from calcium ammonium nitrate) or an isonitrogenous control diet (containing additional urea) and given a top-dress of ground corn without or with LYC, with the fourth week used for data collection. Noncannulated cows were spot measured for CH4 emission by mouth using GreenFeed (C-Lock Inc., Rapid City, SD). The main effect of NO3- decreased CH4 by 17% but decreased dry matter intake by 10% (from 19.8 to 17.8 kg/d) such that CH4:dry matter intake numerically decreased by 8% and CH4:milk net energy for lactation production was unaffected by treatment. Milk and milk fat production were not affected, but NO3- decreased milk protein from 758 to 689 g/d. Ruminal pH decreased more sharply after feeding for cows fed diets without NO3-. Acetate:propionate was greater for cows fed NO3-, particularly when combined with LYC (interaction effect). Blood methemoglobin was higher for cattle fed NO3- than for those fed the control diet but was low for both treatments (1.5 vs. 0.5%, respectively; only one measurement exceeded 5%), indicating minimal risk for NO2- accumulation at our feeding level of NO3-. Although neither apparent organic matter nor neutral detergent fiber digestibilities were affected, apparent N digestibility had an interaction for NO3- × LYC such that apparent N digestibility was numerically lowest for diets containing both NO3- and LYC compared with the other 3 diets. Under the conditions of this study, NO3- mitigated ruminal methanogenesis but also depressed dry matter intake and milk protein yield. Based on the fact that few interactions were detected, LYC had a minimal role in attenuating negative cow responses to NO3- supplementation.

Assessment of daily activity patterns and biomarkers of pain, inflammation, and stress in lactating dairy cows diagnosed with clinical metritis.

The objectives of the present case-control study were to assess (1) daily activity patterns (lying time, number of steps, number of lying bouts, and lying bout duration), and (2) circulating concentrations of biomarkers of pain (substance P), inflammation (haptoglobin), and stress (cortisol) in lactating dairy cows diagnosed with clinical metritis. Lactating dairy cows (n = 200) from 2 commercial dairy herds were enrolled in the present study. Cows diagnosed with clinical metritis (n = 100) at 7 ± 3 d in milk were matched according to lactation and days in milk to cows without clinical metritis (NO-CM; n = 100). On study d 1, clinical metritis was diagnosed (using a Metricheck device, Simcro Tech Ltd., Hamilton, New Zealand) by the presence of watery, reddish, or brownish foul-smelling vaginal discharge, and blood samples were collected for assessment of circulating concentration of substance P, haptoglobin, cortisol, total calcium, ß-hydroxybutyrate, and blood cells. In addition, on study d 1 body condition of cows was visually assessed, and activity monitors were placed on the hind leg of a subset of cows (CM, n = 56; CON, n = 56) and were kept until study d 7. Cows showing any other signs of other diseases were not included in the study. Cows with clinical metritis tended to spend more time lying (CM = 628.92 min/d; NO-CM = 591.23 min/d) compared with NO-CM cows. Activity analysis by parity revealed that primiparous cows with clinical metritis spent more time lying compared with primiparous cows without clinical metritis. However, no differences in daily lying time were observed between multiparous cows with and without clinical metritis. Furthermore, cows in the CM group had a higher circulating concentration of substance P (CM = 47.15 pg/mL; NO-CM = 37.73 pg/mL) and haptoglobin (CM = 233.00 µg/mL; NO-CM = 99.98 µg/mL) when compared with NO-CM cows. Cows with clinical metritis had lower body condition score, and a greater proportion of cows in this group had hypocalcemia when compared with cows without clinical metritis. The circulating concentration of leukocytes and erythrocytes were decreased in cows with clinical metritis compared with cows without clinical metritis. Results from this study showed that concentrations of markers of inflammation, stress, pain, and activity were affected in cows diagnosed with clinical metritis; thus, strategies aimed to minimize the negative effects associated with clinical metritis may be required to improve the welfare of dairy cows.

Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables.

BACKGROUND: Cobalt chloride (CoCl2 ) is administered to racehorses to enhance performance. The purpose of this study was to evaluate the clinical, cardiovascular, and endocrine effects of parenterally administered CoCl2 . OBJECTIVES: To describe the effects of weekly intravenous doses of CoCl2 on Standardbred horses. ANIMALS: Five, healthy Standardbred mares. METHODS: Prospective, randomized, experimental dose-escalation pilot. Five Standardbred mares were assigned to receive 1 of 5 doses of CoCl2 (4, 2, 1, 0.5, or 0.25 mg/kg) weekly IV for 5 weeks. Physical examination, blood pressure, cardiac output, and electrocardiography (ECG) were evaluated for 4 hours after administration of the first and fifth doses. Blood and urine samples were collected for evaluation of cobalt concentration, CBC and clinical chemistry, and hormone concentrations. RESULTS: All mares displayed pawing, nostril flaring, muscle tremors, and straining after CoCl2 infusion. Mares receiving 4, 2, or 1 mg/kg doses developed tachycardia after dosing (HR 60-126 bpm). Ventricular tachycardia was noted for 10 minutes after administration of the 4 mg/kg dose. Increases in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) occurred after administration of all doses (4, 2, 1, 0.5, and 0.25 mg/kg). Profound hypertension was observed after the 4 mg/kg dose (SAP/DAP, MAP [mmHg] = 291-300/163-213, 218-279). Hemodynamics normalized by 1-2 hours after administration. ACTH and cortisol concentrations increased within 30 minutes of administration of all CoCl2 doses, and cardiac troponin I concentration increased after administration of the 4 and 2 mg/kg doses. CONCLUSIONS AND CLINICAL IMPORTANCE: The degree of hypertension and arrhythmia observed after IV CoCl2 administration raises animal welfare and human safety concerns.

Interventional Closure of a Patent Ductus Arteriosus Using an Amplatz Canine Duct Occluder in an Alpaca Cria.

A 6-month old female alpaca cria presented to The Ohio State University for evaluation of a cardiac murmur. Echocardiography revealed a left-to-right shunting patent ductus arteriosus, a restrictive left-to-right shunting perimembranous ventricular septal defect, and secondary moderate left atrial and ventricular dilation. Aortic root angiography demonstrated a type IIA patent ductus arteriosus (PDA). Interventional closure of the PDA was successfully performed, without complication, using an Amplatz canine duct occluder. This case report describes the materials and methods used for interventional closure of a PDA in an alpaca cria.

Pharmacokinetics of intravenous and transdermal fentanyl in alpacas.

The purpose of the study was to determine pharmacokinetics of fentanyl after intravenous (i.v.) and transdermal (t.d.) administration to six adult alpacas. Fentanyl was administered i.v. (2 µg/kg) or t.d. (nominal dose: 2 µg kg-1  hr-1 ). Plasma concentrations were determined using liquid chromatography-mass spectrometry. Heart rate and respiratory rate were assessed. Extrapolated, zero-time plasma fentanyl concentrations were 6.0 ng/ml (1.7-14.6 ng/ml) after i.v. administration, total plasma clearance was 1.10 L hr-1  kg-1 (0.75-1.40 L hr-1  kg-1 ), volumes of distribution were 0.30 L/kg (0.10-0.99 L/kg), 1.10 L/kg (0.70-2.96 L/kg) and 1.5 L/kg (0.8-3.5 L/kg) for V1 , V2 , and Vss , respectively. Elimination half-life was 1.2 hr (0.5-4.3 hr). Mean residence time (range) after i.v. dosing was 1.30 hr (0.65-4.00 hr). After t.d. fentanyl administration, maximum plasma fentanyl concentration was 1.20 ng/ml (0.72-3.00 ng/ml), which occurred at 25 hr (8-48 hr) after patch placement. The area under the plasma fentanyl concentration-vs-time curve (extrapolated to infinity) after t.d. fentanyl was 61 ng*hr/ml (49-93 ng*hr/ml). The dose-normalized bioavailability of fentanyl from t.d. fentanyl in alpacas was 35.5% (27-64%). Fentanyl absorption from the t.d. fentanyl patch into the central compartment occurred at a rate of approximately 50 µg/hr (29-81 µg/hr) between 8 and 72 hr after patch placement.

Lactoferrin reduces mortality in preweaned calves with diarrhea.

Calf diarrhea is the most common reason for mortality and antimicrobial therapy in preweaned calves on dairy farms in the United States. Conventional and organic livestock producers require alternative therapies for calf diarrhea to reduce the necessity of conventional antimicrobials. Alternatives administered for mild cases or early in the disease course may be useful to mitigate disease progression and reduce the likelihood of septicemia and negative sequelae. Lactoferrin is a bioactive protein naturally found in colostrum that has been shown to prevent septicemia in high-risk infants. Among organic producers, garlic extract is widely used for the treatment of disease and perceived to be efficacious. The objectives of the study were to determine the effectiveness of lactoferrin and garlic extract to reduce mortality and culling, improve weight gain, and reduce the duration of disease in preweaned calves with the first diagnosis of diarrhea. In total, 628 calves with diarrhea from a single commercial dairy were enrolled in a blinded, randomized field trial. Calves diagnosed with diarrhea (fecal score ≥3), were randomized to 3 consecutive days of oral garlic extract, lactoferrin, or water (control). Calves were clinically evaluated for up to 10 d. Body weight was measured at enrollment and 10 d later. For calves receiving garlic extract, the risk of death or culling was not significantly different than calves in the control group; however, calves that received lactoferrin had approximately half the risk of death or culling in the 120 d following diagnosis. Additionally, the relative risk of death or culling in the 60 d following diagnosis was significantly lower for the subset of calves with severe diarrhea at enrollment. Neither garlic nor lactoferrin had a significant effect on disease duration or average weight gain during the 10-d period. Lactoferrin significantly reduced mortality and culling when administered to preweaned calves with the first diagnosis of diarrhea; however, additional studies conducted across multiple farms are necessary to corroborate the observed reduction in mortality and culling. If the results are confirmed, lactoferrin may become an important tool to improve treatment outcomes and reduce the necessity of antimicrobials.

Pharmacokinetics and pharmacodynamics of the glucagon-like peptide-1 analog liraglutide in healthy cats.

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that induces glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion. Glucagon-like peptide-1 also increases beta cell mass and satiation while decelerating gastric emptying. Liraglutide is a fatty-acid derivative of GLP-1 with a protracted pharmacokinetic profile that is used in people for treatment of type II diabetes mellitus and obesity. The aim of this study was to determine the pharmacokinetics and pharmacodynamics of liraglutide in healthy cats. Hyperglycemic clamps were performed on days 0 (HGC) and 14 (LgHGC) in 7 healthy cats. Liraglutide was administered subcutaneously (0.6 mg/cat) once daily on days 8 through 14. Compared with the HGC (mean ± standard deviation; 455.5 ± 115.8 ng/L), insulin concentrations during LgHGC were increased (760.8 ± 350.7 ng/L; P = 0.0022), glucagon concentrations decreased (0.66 ± 0.4 pmol/L during HGC vs 0.5 ± 0.4 pmol/L during LgHGC; P = 0.0089), and there was a trend toward an increased total glucose infused (median [range] = 1.61 (1.11-2.54) g/kg and 2.25 (1.64-3.10) g/kg, respectively; P = 0.087). Appetite reduction and decreased body weight (9% ± 3%; P = 0.006) were observed in all cats. Liraglutide has similar effects and pharmacokinetics profile in cats to those reported in people. With a half-life of approximately 12 h, once daily dosing might be feasible; however, significant effects on appetite and weight loss may necessitate dosage or dosing frequency reductions. Further investigation of liraglutide in diabetic cats and overweight cats is warranted.

Impact of oral meloxicam on circulating physiological biomarkers of stress and inflammation in beef steers after long-distance transportation.

Transportation stress can result in significant economic losses to producers due to decreased animal productivity and increased medication costs associated with sickness such as bovine respiratory disease (BRD). Meloxicam (MEL) provides pain relief and anti-inflammatory effects in cattle for several days after a single oral treatment. Our hypothesis was that MEL administration before shipping would reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef steers. Ninety-seven beef steers were blood sampled for baseline biomarker determination and then randomly assigned to receive either 1 mg/kg MEL (n = 49) or a placebo (CONT; n = 48) per os before a 1,316-km transportation event lasting approximately 16 h. Calves were then blood sampled on arrival and 5 d later. Changes in the hemogram, circulating plasma proteins, total carbon dioxide (TCO2), fibrinogen, substance P (SP), cortisol, haptoglobin (Hp)-matrix metalloproteinase-9 (MMP-9) complexes, and tumor necrosis factor α (TNFα) between treatments over time were compared using a mixed effects model with statistical significance designated as P < 0.05. Analysis of covariance was conducted to assess the relationship between circulating MEL concentrations and biomarker changes over time. An increase in neutrophil, platelet, monocyte, white blood cell, and red blood cell counts occurred after transportation (P < 0.0001) and a decrease in lymphocyte count were observed (P < 0.0001). Meloxicam treatment reduced the stress-induced neutrophilia (P = 0.0072) and circulating monocyte count (P = 0.013) on arrival. Mean corpuscle hemoglobin (P = 0.05), mean corpuscle volume (P = 0.05), and lymphocyte count (P = 0.05) were also greater in the CONT calves compared with MEL calves after transportation. Furthermore, Hp-MMP-9 complexes, TCO2, TNFα, plasma proteins, and SP increased and cortisol decreased after shipping (P < 0.01). Meloxicam treatment tended to reduce serum cortisol concentrations (P = 0.08) and there was evidence of a time × treatment interaction (P = 0.04). An inverse relationship between plasma MEL concentrations and circulation cortisol concentrations (P = 0.002) and neutrophil (P = 0.04) and basophil counts (P = 0.03) was also observed. The results suggest that MEL administration may reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef calves.

Fluoroquinolone levels in healthy dog urine following a 20-mg/kg oral dose of enrofloxacin exceed mutant prevention concentration targets against Escherichia coli isolated from canine urinary tract infections.

A 3-day course of oral enrofloxacin is effective for treating uncomplicated urinary tract infection (UTI) in dogs when administered 20 mg/kg Q24H. However, emergence of fluoroquinolone-resistant mutants of uropathogens is a concern. Urine concentrations of enrofloxacin and ciprofloxacin were measured in six healthy dogs following dose of enrofloxacin 20 mg/kg. Mutant prevention concentrations of Escherichia coli isolated from canine UTI were also determined against ciprofloxacin. Urine AUC(24)/MPC ratios considering ciprofloxacin concentrations ranged 3819-7767, indicating that selection of resistant E. coli mutants in dogs with uncomplicated UTIs is unlikely in the bladder given that an AUC(24)/MPC = 39 is considered to be protective against mutant selection for ciprofloxacin. However, additional studies are required to evaluate the effects of this enrofloxacin treatment protocol on bacteria that colonize anatomic sites where fluoroquinolones achieve lower concentrations compared to the urinary bladder.

Effect of Mannheimia haemolytica pneumonia on behavior and physiologic responses of calves during high ambient environmental temperatures.

The objective of this study was to determine the effect of pneumonia during conditions of high (maximum ≥ 32°C) ambient temperatures on physiological and behavioral responses of calves. Eighteen black beef heifers averaging 240 kg were blocked by BW and randomly assigned to 1 of 2 treatment groups: 1) pneumonia induced by bronchoselective endoscopic inoculation with Mannheimia haemolytica (MH; n = 10) and 2) noninoculated controls (CN; n = 8). Nasal passage and rectal temperatures were measured every 2 h for 24 h after challenge and then twice daily for 9 d. Accelerometers, pedometers, and positioning devices monitored cattle behavior within the pen for 9 d after challenge. Blood samples were collected on trial d 0, 0.5, 1, 2, 3, 7, and 9 and were analyzed to determine the concentration of substance P, cortisol, haptoglobin, and metalloproteinase. All calves in the MH group were euthanized and necropsied on trial d 9. All MH calves became clinically ill postchallenge. A treatment × time interaction (P < 0.05) was evident for nasal and rectal temperatures, behavior, weight, and blood analysis. Rectal temperatures in MH were higher (P < 0.01) than CN during the period from 6 to 24 h after challenge. Conversely, nasal passage temperatures were less in MH calves compared with CN at 12 to 22 h after challenge. Calves in MH spent less time at the grain bunk, less time at the hay feeder, and more time lying down during the early pneumonia period compared with CN calves. Also, MH calves had significantly greater concentrations of blood biomarkers of pain (substance P) on d 0.5 (P < 0.01); stress (cortisol) on d 0.5 and 1 (P < 0.01); haptoglobin on d 0.5, 1, 2, 3, 7 (P < 0.01); and metalloproteinase on d 1, 2, and 3 (P < 0.01) compared with CN calves. At necropsy, all MH calves had right cranioventral bronchopneumonia (median lung lesions = 6.8%). Mannheimia haemolytica pneumonia caused significantly more changes in behavior and increased biomarkers during high (maximum ≥32°C) ambient temperatures compared with control calves. The results of this study may guide research in the development of objective assessment tools for management of cattle affected with bovine respiratory disease during extreme summer conditions.

Pharmacokinetics of midazolam after intravenous administration to horses.

REASONS FOR PERFORMING THE STUDY: Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown. OBJECTIVE: To determine the pharmacokinetics and sedative effects of midazolam in horses. STUDY DESIGN: Blinded, randomised, crossover design. METHODS: Midazolam was administered i.v. at either 0.05 or 0.1 mg/kg bwt to 6 horses on 2 occasions at least 7 days apart using a crossover design. Blood samples were collected before and at predetermined times through 24 h after administration. Serum midazolam concentrations were determined by a liquid chromatography tandem-mass spectrometry method. Heart and respiratory rates and indices of sedation, ataxia, and sensitivity to stimuli were recorded before and at predetermined times after midazolam administration. RESULTS: Pharmacokinetic analysis was performed on samples from 5 horses in each group. Median total clearance was 10.6 ml/min/kg (range 6.1-15.2 ml/min/kg) and 10.4 ml/min/kg (range 8.4-17.6 ml/min/kg), and median volume of distribution at steady state was 2094 ml/kg (range 2076-2413 ml/kg) and 2822 ml/kg (range 2270-7064 ml/kg) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Median distribution half-life was 24 min (range 6-42 min) and 39 min (range 33.6-72 min) and median terminal half-life was 216 min (range 120-248 min) and 408 min (range 192-924 min) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Cardiorespiratory parameters and sedation scores did not change. Midazolam caused agitation, postural sway, weakness, and one horse became recumbent after the 0.1 mg/kg bwt dose. CONCLUSIONS: Midazolam produces ataxia and postural sway of short duration after i.v. administration to horses. Sedation was not evident after midazolam administration. Drug redistribution is likely the primary mechanism for the termination of effect. POTENTIAL RELEVANCE: Midazolam produces muscle relaxation but not sedation in adult horses.

Evaluation of regional limb perfusion with erythromycin using the saphenous, cephalic, or palmar digital veins in standing horses.

There are no reported studies evaluating the use of erythromycin for regional limb perfusion (RLP) in horses. Our hypothesis was that using the cephalic and saphenous veins for RLP will enable delivery of therapeutic concentrations of erythromycin to the distal limb. Nineteen healthy horses participated in the study. The cephalic, saphenous or palmar digital (PD) vein was used to perfuse the limb with erythromycin. Synovial samples were collected from the metacarpo/metatarso-phalangeal (MCP/MTP) joint and blood samples were collected from the jugular vein. Maximum concentration (C(max)) of erythromycin in the MCP joint using the cephalic vein was 113 mg/L. The Cmax of erythromycin in the MTP joint using the saphenous vein was 38 mg/L. Erythromycin administered using the PD vein was not detectable in the MCP/MTP joint of four of six horses. Concentrations of erythromycin achieved in the synovial fluid of the MCP/MTP joint were between 152 and 452 times the minimal inhibitory concentration (MIC) for Rhodococcus equi (R. equi). In conclusion, the results indicate that when using the saphenous or cephalic veins for RLP, therapeutic concentrations of erythromycin in the MCP/MTP joint can be consistently reached [corrected].

Cardiac troponin I in calves with congenital heart disease.

BACKGROUND: The association between plasma cardiac troponin I (cTnI) and the magnitude of cardiac enlargement in calves with congenital heart disease (CHD) are not well defined. OBJECTIVE: To investigate the relationship between plasma cTnI concentrations and cardiac size in healthy calves and calves with CHD. ANIMALS: A total of 19 healthy calves (control) and 12 Holstein calves with CHD (patent ductus arteriosus, ventricular septal defect, tetralogy of Fallot or double outlet right ventricle). METHODS: Case control study. All animals underwent a comprehensive transthoracic echocardiographic study to document cardiac health or presence of CHD. The vertebral heart score (VHS) was determined in each animal using right lateral survey radiographic images. Blood samples were collected via jugular venipuncture and plasma cTnI concentration and creatine kinase (CK) activity were determined by a 3rd generation immunoassay and an automatic biochemical analyzer, respectively. Groups were compared using Mann-Whitney U-test and receiver-operating characteristics (ROC) curve analysis. RESULTS: Calves with CHD had significantly larger VHS values and higher plasma cTnI concentrations (P < .001) compared to control. Creatine kinase activity was not different between the control and CHD groups of calves. Diagnostic cutoffs of VHS and plasma cTnI for discrimination of groups were 8.9 vertebrae and 0.035 ng/mL, respectively. The cTnI concentration in plasma was significantly correlated with VHS (r (2) =0.512, P < .001). CONCLUSION AND CLINICAL RELEVANCE: Our results suggest that determination of plasma cTnI concentrations in calves with clinical signs compatible with CHD might prove useful as a guide to quantify cardiac remodeling associated with increased cardiac size.

Characteristics of dairy calf ranches: morbidity, mortality, antibiotic use practices, and biosecurity and biocontainment practices.

The utilization of farming operations specializing in rearing dairy heifer calves has increased since the early 1990s. However, these operations have not been as well characterized as US dairy operations with respect to demographic and health-related measures, particularly during the preweaning period. The objective of this study was to characterize morbidity, mortality, antibiotic use, and biosecurity and biocontainment practices on operations rearing preweaned heifers only or preweaned heifer and bull calves (mixed) in the United States. A cross-sectional survey was performed using a standardized method that included a preletter, initial survey, postcard follow-up, and second survey delivered by mail. Additional follow-up contacts were attempted by telephone. Descriptive statistics for morbidity, mortality, antibiotic use, and biosecurity and biocontainment practices were computed at both the operation and calf levels. The overall response rate was 50%. Crude yearly mortality averaged 6.9% at the calf level, with the median operation reporting 3.6% mortality. Diarrhea was experienced by 18% of calves, with 73% receiving an antibiotic. The median operation reported 20% diarrhea morbidity with 83% receiving an antibiotic. Respiratory disease was experienced by 9.0% of calves, with 82% receiving an antibiotic. The median operation reported 5.3% respiratory morbidity, with 100% receiving an antibiotic. Heifer-only and mixed operations did not differ in operation median morbidity, mortality, or antibiotic treatment rates. Written antibiotic protocols were available on 65% of operations. Medicated milk replacer was used by 56% of operations. Passive immunity was routinely measured by 46% of operations. Direct contact between calves in housing units was not allowed by 45% of operations. Of all farms informed of disease concerns at the source farm, 76% changed their daily routine as a result. Almost all operations uniquely identified calves and recorded mortality. The heifer-only and mixed operations in this study were similar to US dairy operations for key health, antibiotic use, and biosecurity and biocontainment metrics. This research provides initial estimates of key demographics usable by calf ranches, veterinarians, and other professionals serving this segment of the US dairy industry.