Research Update: Energy Strategies for Dry Cows

This information was presented at the 2014 Cornell Nutrition Conference for Feed Manufacturers, organized by the Department of Animal Science In the College of Agriculture and Life Sciences at Cornell University. Softcover copies of the entire conference proceedings may be purchased at http://ansci.cals.cornell.edu/extension-outreach/adult-extension/dairy-management/order-proceedings-resources or by calling (607)255-4285

Dry period plane of energy: Effects on glucose tolerance in transition dairy cows

Overfeeding energy in the dry period can affect glucose metabolism and the energy balance of transition dairy cows with potential detrimental effects on the ability to successfully adapt to early lactation. The objectives of this study were to investigate the effect of different dry cow feeding strategies on glucose tolerance and on resting concentrations of blood glucose, glucagon, insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate (BHB) in the peripartum period. Cows entering second or greater lactation were enrolled at dry-off (57 d before expected parturition) into 1 of 3 treatment groups following a randomized block design: cows that received a total mixed ration (TMR) formulated to meet but not exceed energy requirements during the dry period (n = 28, controlled energy); cows that received a TMR supplying approximately 150% of energy requirements during the dry period (n = 28, high energy); and cows that were fed the same diet as the controlled energy group for the first 28 d, after which the TMR was formulated to supply approximately 125% of energy requirements until calving (n = 28, intermediate energy). Intravenous glucose tolerance tests (IVGTT) with rapid administration of 0.25 g of glucose/kg of body weight were performed 28 and 10 d before expected parturition, as well as at 4 and 21 d after calving. Area under the curve for insulin and glucose, maximal concentration and time to half-maximal concentration of insulin and glucose, and clearance rates were calculated. Insulin resistance (IR) indices were calculated from baseline samples obtained during IVGTT and Spearman rank correlations determined between IVGTT parameters and IR indices. Treatment did not affect IVGTT parameters at any of the 4 time points. Correlation between IR indices and IVGTT parameters was generally poor. Overfeeding cows energy in excess of predicted requirements by approximately 50% during the entire dry period resulted in decreased postpartum basal plasma glucose and insulin, as well as increased glucagon, BHB, and NEFA concentrations after calving compared with cows fed a controlled energy diet during the dry period. In conclusion, overfeeding energy during the entire dry period or close-up period alone did not affect glucose tolerance as assessed by IVGTT but energy uptake during the dry period was associated with changes in peripartal resting concentrations of glucose, as well as postpartum insulin, glucagon, NEFA, and BHB concentrations

Evaluation of Arsenic, Cadmium, Lead and Mercury Contamination in Over-the-Counter Available Dry Dog Foods With Different Animal Ingredients (Red Meat, Poultry, and Fish)

Objectives: To examine the relative levels of heavy metals and arsenic content in commercial dog foods (arsenic, cadmium, lead and mercury) of 51 over-the-counter maintenance or all-life-stage dry dog foods. All products were chosen and segregated based on meat sources (fish, poultry, red-meat—17 products from each category) as animal protein sources being the primary contaminated ingredient due to bioaccumulation.Methods: Inductively coupled plasma mass spectrometry (ICP-MS) was performed on products that were classified as fish, red meat (beef, pork, venison, bison) or poultry (chicken, turkey, duck) based. A non-Gaussian data distribution for each heavy metal within category distribution led to non-parametric statistical testing and median (range) descriptive statistics. Comparison to average human consumption based on mg/megacalorie (Mcal)was also examined.Results: Based on caloric consumption, total arsenic and heavy metal consumption is higher in dogs than in humans; however chronic toxic exposure levels are highly unlikely. Fish-based diets had significantly higher arsenic, cadmium and mercury content than the poultry or red meat-based diets (p < 0.01). Red meat-based diets (beef, venison and bison) had higher lead concentrations than poultry and fish-based diets (p < 0.03).Clinical Significance: Based on the findings, commercial dog foods appear to be safe for chronic consumption and concentrations of the heavy metals were dependent on primary protein sources. Overall, poultry-based diets had relatively lower heavy metal and arsenic content than red meat and fish-based diets. Despite the safety of most pet foods occasional outliers for lead render some concern for chronic exposure based on other species toxicity data and a lack of data in dogs

Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs

The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs. We aimed to examine a small cohort in a pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs. Fourteen dogs were examined in a 24-week randomized cross-over study being provided placebo or CBD/CBDA-rich hemp extract treatment at 2 mg/kg orally every 12 h for each 12-week arm of the study. Serum chemistry, complete blood counts, serum anti-seizure medication (ASM) concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial. Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study. Epileptic seizure frequency decreased across the population from a mean of 8.0 ± 4.8 during placebo treatment to 5.0 ± 3.6 with CBD/CBDA-rich hemp extract (P = 0.02). In addition, epileptic seizure event days over the 12 weeks of CBD/CBDA-rich hemp treatment were 4.1 ± 3.4, which was significantly different than during the 12 weeks of placebo treatment (5.8 ± 3.1; P =0.02). The number of dogs with a 50% reduction in epileptic activity while on treatment were 6/14, whereas 0/14 had reductions of 50% or greater while on the placebo (P = 0.02). No differences were observed in serum zonisamide, phenobarbital or bromide concentrations while on the treatment across groups. Adverse events were minimal, but included somnolence (3/14) and transient increases in ataxia (4/14) during CBD/CBDA-rich hemp extract treatment; this was not significantly different from placebo. This further indicates that providing CBD/CBDA-rich hemp extract during refractory epilepsy (only partially responsive to ASM), in conjunction with other ASM appears safe. Based on this information, the use of 2 mg/kg every 12 h of a CBD/CBDA-rich hemp extract can have benefits in reducing the incidence of epileptic seizures, when used concurrently with other ASMs

Serum Biochemistry and Inflammatory Cytokines in Racing Endurance Sled Dogs With and Without Rhabdomyolysis

Serum muscle enzymes in endurance sled dogs peak within 2–4 days of racing. The object of this study was to compare mid-race serum chemistry profiles, select hormones, markers of inflammation, and the acute phase response in dogs that successfully completed half of the 2015 Yukon Quest sled dog race to their pre-racing samples (n = 14), as well as mid-race samples of successful dogs to those who developed clinical exertional rhabdomyolysis (ER) (n = 5). Concentrations of serum phosphorus in ER dogs were significantly elevated compared to healthy dogs (median 5.5 vs. 4.25 mg/dL, P < 0.01) at mid race. ALT, AST, and CK show a significant increase from pre-race baseline to mid-race chemistries (P < 0.01), with more pronounced increases in dogs with ER compared to healthy racing dogs (CK- median 46,125 vs. 1,743 U/L; P < 0.01). Potassium concentrations were significantly decreased from pre-race baselines in all dogs (median 5.1 vs. 4.5 mEq/L; P < 0.01), and even lower in dogs with ER (median 3.5 mEq/L; P < 0.01) mid-race. No changes in serum pro-inflammatory cytokine concentrations were noted in any groups of dogs. C-reactive protein was elevated in both groups of dogs, but significantly higher in those with ER compared with healthy dogs mid-race (median 308 vs. 164 ug/mL; P < 0.01). Healthy dogs may have CK elevations over 10,000 U/L, and dogs with ER were over 30,000 U/L. Although potassium decreases in healthy endurance sled dogs during racing, it remains in the normal laboratory reference range; however ER dog potassium levels drop further to the point of hypokalemia. Lastly increases in CRP may be reflective of a physiological response to exercise over the course of a race; however high CRP in ER dogs may be capturing an early acute phase response

Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis)

IntroductionCannabinoids are increasingly popular in human and veterinary medicine and have been studied as an alternative treatment for a wide range of disorders. The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol (CBD)-/cannabidiolic acid (CBDA)-rich hemp oil (CBD/ArHO) in juvenile cynomolgus macaques (Macaca fascicularis).MethodsAfter a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered (n = 4 per dose) once daily for 14 days and blood was collected at 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, and 24-h, and on Days 7 and 14, to quantify serum cannabinoid concentrations by high-performance liquid chromatography–tandem mass spectrometry. Serum biochemistries and complete blood counts were performed on Days 0, 1, and 14.ResultsThe maximum mean serum concentration (Cmax) of CBDA was 28.6–36.2 times that of CBD at 4 and 8 mg/kg. At 8 mg/kg, the Cmax of CBD was 1.4 times higher (p = 0.0721), and CBDA was significantly 1.8 times higher (p = 0.0361), than at 4 mg/kg. The maximum mean serum concentration of ∆9-tetrahydrocannabinol (THC) was 4.80 ng/mL at 8 mg/kg. Changes in serum biochemistries and complete blood counts over time were not clinically significant.DiscussionGiven the low serum CBD concentrations, the doses and frequency used in this study may be insufficient for a therapeutic effect of CBD in particular; therefore, clinical studies are needed to determine the therapeutic dose of CBD and CBDA for macaques, which may differ based on the disorder targeted

Insulin-Like Growth Factor-1 and Selected Insulin-Like Growth Factor Binding Protein Concentrations during an Ultramarathon Sled Dog Race

The objective of this study was to investigate the effects of running a 1000-mile (1600 km) endurance sled dog race on serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding proteins 1 and 3 (IGFBP-1 and IGFBP-3). Serum was examined from 12 sled dogs prior to the race, at midrace (approximately 690 km), and again at the finish. IGF-1, IGFBP-1, and IGFBP-3 were assessed using radioimmunoassay or enzyme linked immune-absorbance assays. Mean prerace concentrations were significantly higher than midrace and end-race concentrations at 215.93 ± 80.51 ng/mL, 54.29 ± 25.45 ng/mL, and 55.53 ± 28.25 ng/mL, respectively (P<0.001). Mean IGFBP-1 concentrations were not different across these time periods at 24.1 ± 15.8 ng/mL, 25.7 ± 14.0 ng/mL, and 26.6 ± 17.6 ng/mL, respectively. IGFBP-3 concentrations showed a modest significant decrease across time periods at 3,067 ± 2,792 ng/mL, 2,626 ± 2,310 ng/mL, and 2,331 ± 2,301 ng/mL, respectively (P<0.01). Endurance sled dogs show a precipitous drop in serum IGF-1 concentrations. These differences may be related to fuel utilization and excessive negative energy balance associated with the loss of body condition during racing. The relative stability of IGFBP-1 and IGFBP-3 suggests that IGF-1 anabolic signaling is diminished during ultramarathon racing. Further studies comparing the influence of time and duration of exercise versus negative energy balance on serum IGF-1 status are warranted to better understand exercise versus negative energy balance differences

Serum Cannabinoid 24 h and 1 Week Steady State Pharmacokinetic Assessment in Cats Using a CBD/CBDA Rich Hemp Paste

Hemp based cannabinoids have gained popularity in veterinary medicine due to the potential to treat pain, seizure disorders and dermatological maladies in dogs. Cat owners are also using hemp-based products for arthritis, anxiety and neoplastic disorders with no studies assessing hemp cannabinoids, namely cannabidiol efficacy, for such disorders. Initial twenty-four pharmacokinetic and chronic dosing serum concentration in cats are sparse. The aim of our study was to assess 8 cats physiological and 24 h and 1-week steady state pharmacokinetic response to a cannabidiol (CBD) and cannabidiolic acid (CBDA) rich hemp in a palatable oral paste. Using a standard dose of paste (6.4 mg/CBD + CBDA 5.3 mg/gram) across 8 cats weighing between 4.2 and 5.4 kg showed an average maximal concentration of CBD at 282.0 ± 149.4 ng/mL with a half-life of ~2.1 ± 1.1 h, and CBDA concentrations of 1,011.3 ± 495.4 ng/mL with a half-life of ~2.7 ± 1.4 h, showing superior absorption of CBDA. After twice daily dosing for 1 week the serum concentrations 6 h after a morning dosing showed that the acidic forms of the cannabinoids were approximately double the concentration of the non-acidic forms like CBD and Δ9- tetrahydrocannabinol (THC). The results of this study compared to two other recent studies suggest that the absorption in this specific paste product may be superior to oil bases used previously, and show that the acidic forms of cannabinoids appear to be absorbed better than the non-acidic forms. More importantly, physical and behavioral examinations every morning after dosing showed no adverse events related to neurological function or behavioral alterations. In addition, bloodwork after 1 week of treatment showed no clinically significant serum biochemical alterations as a reflection of hepatic and renal function all remaining within the reference ranges set by the diagnostic laboratory suggesting that short-term treatment was safe

Evaluation of vegetable protein in canine diets: assessment of performance and apparent ileal amino acid digestibility using a broiler model

Recent technological advances in the human food industry with respect to meat processing have decreased the availability of animal proteins to the pet food industry which typically formulates diets with an excess of animal protein. In the long term, this is not sustainable; thus, alternative protein sources need to be investigated. This study examined three canine diets, comparing a typical animal protein-based diet (control) with two experimental diets where the animal protein was substituted in part with vegetable protein (formulated based either on total protein or amino acid content) using a broiler model. Each diet was fed to six cages each containing two birds from day 15, 18 cages in total (36 birds). Excreta were collected from days 19 to 21. On day 23, birds were euthanized and weighed, and their ileal digesta were collected and pooled for each cage. In addition, one leg per cage was collected for evaluation of muscle mass. Results showed no significant difference in animal performance (feed intake or live weight gain) or muscle to leg proportion across the diets. Birds fed the control diet and the diet balanced for amino acid content exhibited the greatest coefficients of apparent metabolizability for nitrogen (p < .001). Birds fed the diets that contained partial replacement of animal with vegetable protein generally had greater ileal digestibility of amino acids compared to birds fed the control (animal protein) diet. Analysis of excreta showed no dietary difference in terms of dry matter content; however, birds fed the diet balanced for total protein and the diet balanced for amino acid content had significantly greater excreta nitrogen than the control (p = .038). Overall, the study suggests vegetable proteins when formulated based on amino acid content are a viable alternative to animal proteins in canine diets