Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO₂) into milk. The goal of this study was to evaluate the presence of potential in vivo drug‐drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO₂ was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO₂ into milk was observed. The milk‐to‐plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO₂ were not modified in the presence of OFZ. The pattern of MNPSO₂ excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO₂) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO₂) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO₂.     

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows

A transdermal formulation of the nonsteroidal anti‐inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single‐dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high‐pressure liquid chromatography with mass spectroscopy (HPLC ‐MS ). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (T max) was 2.81 hr, and the maximum drug concentration was 1.08 μg/ml. The mean terminal half‐life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg^?1, and volume of distribution of fraction (V z/F ) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses.     

Safety of standardized Macleaya cordata extract in an eighty‐four‐day dietary study in dairy cows

The objective of this study was to evaluate the safety of a standardized Macleaya cordata Extract Product (MCEP) containing the quaternary benzophenanthridine alkaloids, sanguinarine and chelerythrine, when fed to dairy cows. Thirty‐six dairy cows were randomized into three groups with twelve cows/treatment in two replica pens for each treatment group: control (C) without MCEP added to feed, treatment 1 (SANG‐1000) with MCEP added to feed at 1,000 mg/animal/day (1.5 mg/kg bw/day) and treatment 2 (SANG‐10000) with MCEP added to feed at 10,000 mg/animal/day (15.5 mg MCEP/kg bw/day). After two weeks of acclimation, animals were observed for an 84‐day experimental period, with body weight, feed intake and milk production measured daily. Milk composition was analysed every two weeks. Haematological analyses were performed on Day 0 and Day 84, and clinical chemistry analyses were performed on Day 84 of the study. There was no statistically significant difference (p > .10) among the three groups on body condition score, milk production or milk composition over the study period. There were no significant differences in body weight gain or feed consumption among the three groups. Animals in the SANG‐10000 group had significantly higher mean corpuscular volume (MCV) than the C group (p < .1) and lower mean corpuscular haemoglobin concentration (MCHC) than the SANG‐1000 group (p < .1). Concentrations of sanguinarine and chelerythrine in milk samples collected on Day 84 were below the detection limit (LOD) as measured by high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS/MS). In conclusion, this study presents compelling data supporting the hypothesis that the test product MCEP, when included in the TMR at up to 10,000 mg/animal/day (15.5 mg MCEP/kg bw/day), is well tolerated by dairy cows.     

Hyperglycaemia in transition dairy cows: Effects of lactational stage and conjugated linoleic acid supplementation on glucose metabolism and turnover

Supplementing conjugated linoleic acid ( CLA ) is supposed to spare glucose due to the milk fat‐depressing effect of the trans ‐10, cis ‐12 CLA isomer, and allows repartitioning nutrients despite an energy deficiency in early lactation. However, there is still a lack of knowledge in terms of the dynamic pattern of the glucose turnover in transition dairy cows. We hypothesized that dairy cows supplemented with CLA have an altered rate of glucose turnover and insulin sensitivity during early lactation. We conducted three consecutive hyperglycaemic clamps (HGC ) in weeks ?2, +2 and +4 relative to parturition in Holstein cows supplemented daily either with 70 g of lipid‐encapsulated CLA (6.8 g trans ‐10, cis ‐12 and 6.6 g of the cis ‐9, trans ‐11 CLA isomer; CLA ; n  = 11) or with 56 g of control fat ( CON ; n  = 11). From week ?3 up to week +4 relative to parturition, milk yield and dry matter intake (DMI ) were recorded daily, while body weight (BW ) and milk composition were obtained once weekly. Blood samples were taken once weekly and every 30 min during the HGC . Plasma was analysed for concentrations of glucose, fatty acids (FFA ), beta‐hydroxybutyrate (BHB ), insulin, triglycerides and cholesterol. The CLA supplementation did not affect performance and metabolic parameters except for BHB and cholesterol. Furthermore, insulin concentrations and insulin sensitivity were affected by treatment. During the HGC in early lactation, insulin response was lower and decrease in FFA and BHB greater compared with the HGC in week ?2 although glucose target concentration achieved during the steady‐state period was similar for all three HGC . Our findings in terms of insulin and cholesterol suggest that body reserves are preserved through CLA feeding without restraining animal's performance. Furthermore, CLA effects on cholesterol and triglyceride concentrations indicated beneficial effects on hepatic lipid export contributing to an improved efficiency of prevailing metabolites in circulation.     

Effects of continuous low dose infusion of lipopolysaccharide on inflammatory responses,milk production and milk quality in dairy cows

The objective of this study was to evaluate the effects of continuous low dose infusion of lipopolysaccharide (LPS) on inflammatory responses and milk production and quality in lactating dairy cows. Eight Holstein cows were assigned to two treatments in a cross‐over experimental design. Cows were infused intravenously either with saline solution or with saline solution containing LPS from Escherichia coli O111:B4 at a dose of 0.01 μg LPS/kg body weight for approximately 6 hr each day during a seven‐day trial. The clinical symptoms and milk production performance were observed. Milk samples were analysed for conventional components, fatty acids and amino acids. And jugular vein and mammary vein plasma samples were analysed for concentrations of cytokines and acute phase proteins. LPS infusion decreased feed intake and milk yield. An increase in body temperature was observed after LPS infusion. LPS infusion also increased plasma concentrations of interleukin‐1β, serum amyloid A, LPS‐binding protein, C‐reactive protein and haptoglobin. LPS infusion decreased the contents of some fatty acids, such as C17:1, C18:0, C18:1n9 (trans) and C18:2n6 (trans), and most amino acids except for methionine, threonine, histidine, cysteine, tyrosine and proline in the milk. The results indicated that a continued low dose infusion of LPS can induce an inflammatory response, decrease milk production and reduce milk quality.     

Performance,rumen fermentation and blood metabolites of dairy calves fed starter mixtures supplemented with herbal plants,essential oils or monensin

This study evaluated the supplementation effects of three herbal plants (thyme [THY], eucalyptus [EUC] and celery [CEL]), a commercial phytogenic additive ?containing essential oils (PFA‐EO, Digestarom^® P.E.P.) and monensin (MON) in calf starter on performance, rumen fermentation and blood metabolites during pre‐ (days 3–55) and post‐weaning (days 56–70). Sixty‐six Holstein dairy calves (3 days of age, 41.2 ± 3 kg of BW) were allocated to one of six starters supplemented with: (i) no additives (CON), (ii) MON (30 mg/kg), (iii) THY (23 g/kg), (iv) CEL (23 g/kg), (v) EUC (23 g/kg) and (vi) PFA‐EO (3 g/kg). All the calves were offered starters ad libitum plus 6 L of whole milk daily. Starter intake tended to be the highest in calves fed PFA‐EO and THY; intermediate in calves fed CON, MON and EUC; and the lowest in those fed CEL. Average daily gain (ADG) and feed efficiency (FE) remained unaffected by dietary treatments during the pre‐weaning. During the post‐weaning period, ADG and FE ?were greatest in calves fed EUC followed by those fed CON, MON, PFA‐EO and THY, and then in those fed CEL. No differences were observed among the treatments in skeletal growth, faecal score, rumen pH or ammonia‐N concentration. Compared to calves fed CON and MON, those fed the herbal plants or PFA‐EO tended to recorded higher molar proportions of acetate and butyrate, and the acetate: propionate ratio. Blood malondialdehyde level did not differ among treatments, but calves on CON had the highest glucose concentration, and those fed PFA‐EO recorded the highest value for β‐hydroxyl butyrate on day 70. In conclusion, the results indicate that the three herbs and PFA‐EO are capable of modulating some of the rumen fermentation parameters and blood metabolites as well as eucalyptus could potentially be a better alternative to monensin for improving post‐weaning performance.     

The effect of dietary supplementation with Aurantiochytrium limacinum on lactating dairy cows in terms of animal health,productivity and milk composition

The aim of this study was to investigate the effect of dietary supplementation with the docosahexaenoic acid (DHA )‐rich microalgae, Aurantiochytrium limacinum (AURA ), on a variety of health and productivity parameters in lactating cows. Twenty‐four cows were blocked by parity and number of days in milk and then randomly assigned to a control (CON ; n  = 12) group with no algal supplementation, or a treatment group (AURA ; n  = 12) provided with 100 g AURA  cow^?1 day^?1 or 16 g DHA  cow^?1 day^?1. A variety of health and productivity measurements were taken, and results indicated that supplementation had no negative effects on animal health in terms of somatic cell count, haematological and biochemical blood parameters, while body condition was marginally improved by algal supplementation. No differences were found for the various production parameters measured; however, a tendency towards increased milk production was observed for the AURA group during the final stage of the study (+4.5 kg cow^?1 day^?1, day 78–84). The fatty acid profile of milk was improved by supplementation, with significantly lower saturated fatty acids, significantly higher omega‐3 fatty acids and an improved omega‐3/omega‐6 ratio observed when compared to the control group. The amount of DHA in the milk of cows provided 105 g AURA  head^?1 day^?1 was 4.7 mg/100 g milk with a peak transfer efficiency from feed to milk at day 49 of 8.3%. These results indicate that supplementation with 105 g AURA  head^?1 day^?1 resulted in the successful enrichment of milk with DHA without negatively impacting the health or productivity of the animals.     

Amino acid profiles of rumen undegradable protein: a comparison between forages including cereal straws and alfalfa and their respective total mixed rations

Optimizing the amino acid (AA) profile of rumen undegradable protein (RUP) can positively affect the amount of milk protein. This study was conducted to improve knowledge regarding the AA profile of rumen undegradable protein from corn stover, rice straw and alfalfa hay as well as the total mixed ratio diets (TMR) based on one of them as forage source [forage‐to‐concentrate ratio of 45:55 (30% of corn stover (CS), 30% of rice straw (RS), 23% of alfalfa hay (AH) and dry matter basis)]. The other ingredients in the three TMR diets were similar. The RUP of all the forages and diets was estimated by incubation for 16 hr in the rumen of three ruminally cannulated lactating cows. All residues were corrected for microbial colonization, which was necessary in determining the AA composition of RUP from feed samples using in situ method. Compared with their original AA composition, the AA pattern of forages and forage‐based diets changed drastically after rumen exposure. In addition, the extent of ruminal degradation of analysed AA was not constant among the forages. The greatest individual AA degradability of alfalfa hay and corn stover was Pro, but was His of rice straw. A remarkable difference was observed between microbial attachment corrected and uncorrected AA profiles of RUP, except for alfalfa hay and His in the three forages and TMR diets. The ruminal AA degradability of cereal straws was altered compared with alfalfa hay but not for the TMR diets. In summary, the AA composition of forages and TMR‐based diets changed significantly after ruminal exposure, indicating that the original AA profiles of the feed cannot represent its AA composition of RUP. The AA profile of RUP and ruminal AA degradability for corn stover and rice straw contributed to missing information in the field.     

Heritability and genetic correlations between rumination time and production traits in Holstein dairy cows during different lactation phases

So far, rumination has been used as a proxy for monitoring dairy cow health at farm level. However, investigating its genetic aspects as well as its correlation with other important productive traits may turn this management tool into a new informative selection criterion. However, scientific evidences on genetic correlation among rumination time (RT) and milk production and milk composition are still scarce. Therefore, the objective of this study was to estimate the heritability of RT across three lactation phases and its genetic correlation with milk production, milk composition and somatic cell count (SCC). Results of our study showed that heritability for RT was 0.34 and was constant across lactation. The mean genetic correlations between RT and milk production and composition traits were 0.07 (milk production), ?0.07 (protein yield), ?0.31 (fat yield), and ?0.32 (fat/protein ratio). The mean genetic correlation between RT and the SCC was 0.05.     

Single step genomic evaluation for female fertility in Nordic Red dairy cattle

Joint Nordic (Denmark, Finland, Sweden) genetic evaluation of female fertility is currently based on the multiple trait multilactation animal model (BLUP). Here, single step genomic model (ssGBLUP) was applied for the Nordic Red dairy cattle fertility evaluation. The 11 traits comprised of nonreturn rate and days from first to last insemination in heifers and first three parities, and days from calving to first insemination in the first three parities. Traits had low heritabilities (0.015–0.04), but moderately high genetic correlations between the parities (0.60–0.88). Phenotypic data included 4,226,715 animals with records and pedigree 5,445,392 animals. Unknown parents were assigned into 332 phantom parent groups (PPG). In mixed model equations animals were associated with PPG effects through the pedigree or both the pedigree and genomic information. Genotype information of 46,914 SNPs was available for 33,969 animals in the pedigree. When PPG used pedigree information only, BLUP converged after 2,420 iterations whereas the ssGBLUP evaluation needed over ten thousand iterations. When the PPG effects were solved accounting both the pedigree and the genomic information, the ssGBLUP model converged after 2,406 iterations. Also, with the latter model breeding values by ssGBLUP and BLUP became more consistent and genetic trends followed each other well. Models were validated using forward prediction of the young bulls. Reliabilities and variance inflation of predicted genomic breeding values (values for parent averages in brackets) for the 11 traits ranged 0.22–0.31 (0.10–0.27) and 0.81–0.95 (0.83–1.06), respectively. The ssGBLUP model gave always higher validation reliabilities than BLUP, but largest increases were for the cow fertility traits.