Pharmacokinetics of lidocaine in serum and milk of mature Holstein cows

The purpose of this study was to evaluate the pharmacokinetics of lidocaine in mature Holstein cows following an inverted L and caudal epidural nerve block. Plasma and milk concentrations were determined using high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following administration via inverted L nerve block, serum T_max was 0.521 ± 0.226 h and serum C_max was 572 ± 207 ng/mL. Serum AUC was 1348 ± 335 ng·h/mL. Apparent serum t_½β was 4.19 ± 1.69 h and MRT was 5.13 ± 2.33 h with clearance uncorrected for the extent of absorption of 2.75 ± 0.68 L/kg/h. The last measurable time of lidocaine detection in serum was 8.5 ± 1.4 h with a mean concentration of 51 ± 30 ng/mL. Milk T_max was detected at 1.75 ± 0.46 h with C_max of 300 ± 139 ng/mL. Milk AUC till the last time was 1869 ± 450 ng·h/mL with the mean AUC milk to AUC serum ratio of 1.439 ± 0.374. The last measurable time of lidocaine detection in milk was 32.5 ± 16.2 h with a mean concentration of 46 ± 30 ng/mL. There was no detectable lidocaine concentration in any samples following caudal epidural administration.     

Pharmacokinetics of phenylbutazone in plasma and milk of lactating dairy cows

Phenylbutazone was administered intravenously (i.v.) to a group of four lactating cows at a dosage of 6 mg/kg body weight. Whole plasma, protein-free plasma and milk were analysed for phenylbutazone residues. Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a non compartmental method. In regards to whole plasma data, the mean volume of distribution at steady state ( V _ss), was 147 mL/kg body weight, with a mean (± SEM) terminal elimination half-life ( t _1/2) of 40 ± 6 h. The mean clearance ( Cl ) was 3 mL/h/kg body weight. The V _ss as determined from the protein-free plasma fraction was 50 021 mL/kg body weight. This larger V _ss of free phenylbutazone compared to total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t _1/2 of free phenylbutazone was 39 ± 5 h. This similarity to the t _1/2 estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. Mean t _1/2 as determined from milk, applying a urinary excretion rate model, was 47 ± 4 h. Milk clearance of phenylbutazone was 0.009 mL/h/kg body weight, or about 0.34% of total body clearance. Furthermore, evidence suggests that phenylbutazone either binds to milk proteins, or is actively transported into milk, as its concentration in milk was greater than that predicted due to a simple partitioning from plasma into milk.     

Changes in plasma ghrelin and growth hormone concentrations in mature Holstein cows and three-month-old calves

We measured changes in plasma ghrelin and GH concentrations in mature Holstein cows and 3-mo-old female Holstein calves fed at scheduled times. Our objective was to determine the characteristics of ghrelin secretion in dairy cattle and its influence on GH. Animals were fed at 0800 and 1600 for 2 wk before and during experiments. Plasma was sampled for 24 h at 2-h intervals in Exp. 1. In mature cows, plasma ghrelin concentrations decreased (P < 0.01) just after 0800 but not at the 1600 feeding. Ghrelin concentrations were lower (P < 0.01) in calves than in mature cows and they did not decrease after feeding in calves. The temporal relationship between ghrelin and GH remained unclear. In Exp. 2, plasma was sampled 2 h before and after both morning and evening feedings at 20-min intervals. Plasma ghrelin concentrations decreased (P < 0.05) 40 min after 0800 feeding and 60 min after 1600 feeding in mature cows. These results indicate that in mature cows, plasma ghrelin concentration decreased after feeding, but this decrease was not evident in 3-mo-old calves. Further studies are required to define the relationship between plasma ghrelin and GH concentrations.     

Stillbirth parturition reduces milk production in Holstein cows

Stillbirth is defined as calf mortality shortly before, during, or shortly after parturition. Economic losses to the dairy industry in the U.S. just due to the loss of replacement heifers were estimated to be $125 million per year. Our objective in this study was to evaluate the effect of stillbirth on the dam's subsequent lactation. Data were collected from 20 farms in the U.S.A. (19 from NY, one from IN) from May 2005 until September 2006. Calving-ease scores (scale of 1-5; no problem and extreme difficulty, respectively) and stillbirths were recorded by farm personnel. We used 32,299 calvings for the final analysis where 6.5% of the calvings were stillbirths. The incidence of stillbirths for primiparous cows was 10.7% (of 11,891) and 4% (of 20,408) for multiparous cows. Stillbirth parturition significantly reduced milk production (-1.1 kg/day). The losses in milk production were evaluated in a generalized mixed linear model analysis. The daily milk production for cows with stillbirths was 34.2 kg, compared to 35.3 kg for the cows that had a live calf. Milk-production reduction was greatest early in lactation and declined afterwards. Economic losses from stillbirths include not just the lost calf, the reduced survival, and increased days open but also the decreased milk yield.     

Comparison of milk and plasma pharmacokinetics of meloxicam in postpartum versus mid‐lactation Holstein cows

The objective of this study reported here was determine whether differences occurred in meloxicam pharmacokinetics between postpartum cows and mid‐lactation cows. Preliminary data from a separate study (P. J. Gorden, unpublished data) in postpartum cows demonstrated elevated plasma and milk concentration profiles compared to previously published data (Malreddy, Coetzee, KuKanich, & Gehring, 2013 ). Two different groups were enrolled, each with 10 cows. The treatment group (TRT) was postpartum cows treated with meloxicam, and the positive control (PC) group was cows in mid‐lactation treated with meloxicam. Plasma and milk meloxicam concentrations between the TRT and PC group were compared. Significant differences in meloxicam concentration in plasma were determined at all time points from 8 hr to 120 hr post‐treatment. In milk, there was a treatment (p = .003), time (p < .001), and treatment by time interaction (p < .001). Significant differences in milk meloxicam concentration were determined at all time points from 8 hr to 96 hr post‐treatment, except for the 16‐hr time point. The time needed for meloxicam to no longer be detected in milk of the TRT group was longer compared to the PC group, indicating that a longer milk withdrawal is needed. These data suggest higher bioavailability as the underlying mechanism. Further research is needed to determine the mechanisms underlying differences this outcome.     

Pharmacokinetics of phenylbutazone given intravenously or orally in mature Holstein bulls

Six mature Holstein bulls were each given 10 mg of phenylbutazone (PBZ)/kg of body weight, PO. Of the 6 bulls, 3 were given 10 mg of PBZ/kg by rapid IV administration 4 weeks later. Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling (sum of exponential functions). The harmonic mean of the biologic half-life of PBZ was 62.6 +/- 12.9 hours after oral administration and 61.6 +/- 7.2 hours after IV administration. The mean residence time was 94.61 +/- 8.44 hours and 90.49 +/- 8.93 hours for oral and IV administration, respectively. The mean total body clearance was 0.0015 +/- 0.0003 L/h/kg, with the mean apparent volume of distribution 0.134 +/- 0.021 L/kg. Mean bioavailability was 73 +/- 2% after oral administration. Phenylbutazone was adequately absorbed from the gastrointestinal tract in bulls. The apparent volume of distribution was small, indicating that PBZ distributed mainly into plasma and extracellular fluid. The total body clearance was also small, which accounted for the long half-life of PBZ in bulls.     

Carbon kinetics of milk formation in Holstein cows in late lactation

Carbon transfer to milk in Holstein cows in late lactation was measured by introducing changes in the natural stable carbon isotope composition of the feed. Six Holstein cows in mid-lactation were placed on a diet naturally low in 13C (-25.0% vs Pee Dee belemnite [PDB] an international carbon isotope standard), based on alfalfa-barley, and six others were placed on a diet naturally enriched in 13C (-11.5% vs PDB), based on corn. After a 7-wk equilibration period on these diets, three cows were switched from alfalfa-barley to corn, and three were switched from corn to alfalfa-barley. The three other cows in each group served as controls. 13C/12C ratios were measured in daily morning milk samples during the week before and for 6 wk after the changes in diet. After the diets had been switched, milk isotope ratios rapidly approached the isotopic composition of the new diet, indicating rapid transfer of dietary carbon into milk. The data were consistent with a model whereby milk was synthesized from a single precursor pool that responded rapidly to dietary perturbation. The milk precursor pool had a half-life of approximately .9 d and had a mass of approximately 7 kg of carbon, which was renewed daily by the entry of 5 kg of digestible dietary carbon.     

复合益生菌制剂对奶牛泌乳性能及乳品质的影响

为研究复合益生菌制剂对奶牛泌乳性能及乳品质的影响,试验选取45头泌乳期相近的荷斯坦奶牛,随机分为3组,对照组、试验1组、试验2组,每组3个重复,每个重复5头。对照组饲喂基础日粮,试验1、2组分别在基础日粮中添加1%、2%的复合益生菌制剂,试验期为60d。结果表明:试验2组在第10、30、60天奶牛产奶量较对照组分别提高2.28%、0.62%、9.08%(P<0.05),试验1组在第10、60天较对照组分别提高4.6%、8.9%(P<0.05);第30天时,试验1、2组乳中总固形物含量较对照组均显著性提高(P<0.05),乳糖率、乳蛋白率、乳脂率之间差异不显著(P>0.05);第60天时,与对照组相比,试验1、2组乳中乳糖率分别提高了4.41%、7.02%(P<0.05),乳蛋白率提高了4.16%、9.97%(P<0.05),总固形物含量提高了2.44%、3.02%(P<0.05),乳脂率含量之间差异不显著(P>0.05)。综上,日粮中添加复合益生菌制剂可有效提高奶牛产奶量及乳品质,且添加2%复方益生菌制剂效果更优。     

不同程度热应激对泌乳中期奶牛产奶量和乳成分的影响

选取36头临床健康、头胎、泌乳中期奶牛,通过实时监控外界温湿度指数,结合奶牛呼吸、心率、肛温等生理指标,确定奶牛热应激状态,并测定奶牛产奶量和乳成分。结果,与无热应激相比,中度热应激使奶牛日均产奶量降低16.33%,轻度热应激对此影响不明显。中度热应激奶牛乳脂率较轻度热应激显著降低,但与无热应激组相比差别不显著。轻度热应激使奶牛乳蛋白水平极显著降低,但随热应激程度加深,乳蛋白水平有升高趋势。试验结果表明:不同程度热应激对泌乳中期奶牛产奶量和乳成分有不同影响。     

荷斯坦奶牛体型线性性状与产奶量的相关性分析

对新疆荷斯坦奶牛的产奶量与体型线性性状进行了相关。通径分析。结果表明，荷斯坦奶牛的乳房纵沟深，后乳房宽，后乳房高与产奶量呈中等正相关，体高，体长，尻宽，尻长与产奶量呈弱相关；后乳房宽，乳房纵沟深是直接影响产奶量的重要性状，且是正身作用；后乳房高对产奶量起负面影响。其间接作用大。     

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.     

Genome-wide association for milk production and lactation curve parameters in Holstein dairy cows

The aim of this study was to identify genomic regions associated with 305-day milk yield and lactation curve parameters on primiparous (n = 9,910) and multiparous (n = 11,158) Holstein cows. The SNP solutions were estimated using a weighted single-step genomic BLUP approach and imputed high-density panel (777k) genotypes. The proportion of genetic variance explained by windows of 50 consecutive SNP (with an average of 165 Kb) was calculated, and regions that accounted for more than 0.50% of the variance were used to search for candidate genes. Estimated heritabilities were 0.37, 0.34, 0.17, 0.12, 0.30 and 0.19, respectively, for 305-day milk yield, peak yield, peak time, ramp, scale and decay for primiparous cows. Genetic correlations of 305-day milk yield with peak yield, peak time, ramp, scale and decay in primiparous cows were 0.99, 0.63, 0.20, 0.97 and −0.52, respectively. The results identified three windows on BTA14 associated with 305-day milk yield and the parameters of lactation curve in primi- and multiparous cows. Previously proposed candidate genes for milk yield supported by this work include GRINA, CYHR1, FOXH1, TONSL, PPP1R16A, ARHGAP39, MAF1, OPLAH and MROH1, whereas newly identified candidate genes are MIR2308, ZNF7, ZNF34, SLURP1, MAFA and KIFC2 (BTA14). The protein lipidation biological process term, which plays a key role in controlling protein localization and function, was identified as the most important term enriched by the identified genes.     

Adhesion molecules and lymphocyte subsets in milk and blood of periparturient Holstein cows.

Migration of leukocytes into the mammary gland is an essential element of resistance to infection which is likely influenced by expression of adhesion molecules. The contribution of subsets to mammary gland resistance remains unclear. Mononuclear cells from milk and blood of dairy cows were examined for variation in CD4+, CD8+, and WC1+ (Workshop Cluster 1; marker for gammadelta T cells) lymphocyte phenotypes and expression of LFA-1 and L-selectin at several time points during the periparturient period and at Week 16 of lactation. Proportions of CD4+ T cells were higher (p < or = 10.05) in blood than milk at all times between Week 0 and Week 16 relative to calving; the inverse was true of CD8+ cells. Expression of L-selectin was lower (p < or = 0.05) on CD4+ cells and higher on CD8+ cells from milk. The WC1+ subset was more frequent in blood than in milk except at calving when the opposite was true. After calving, proportions of L-selectin+ WC1+ cells decreased steadily to Week 16. Expression of LFA-1 was examined on mononuclear cell populations and found to be lower on milk cells and did not vary over time. We conclude that proportions of T cells subsets differ significantly between blood and milk, particularly around calving. Corresponding variations in L-selectin expression may indicate a role for this molecule in regulating the movement of CD8+ and WC1+ T cells into the bovine mammary gland.     

Effect of genetic selection for milk yield and increased milking frequency on plasma growth hormone and prolactin concentration in Holstein cows

Fifty Holstein cattle, either second to fourth generation daughters of cows randomly bred to non-commercial sires originating in the Virginia Tech dairy herd (estimated mean PDM84 = -455 kg, control animals), or daughters of cows bred to commercially available sires (mean PDM84 = +368 kg, selection animals), were randomly assigned to be milked twice or thrice daily starting at parturition. Serial blood samples were collected via jugular cannulae at 30, 90 and 200 d post-partum (DPP) during both the first and second lactations. Blood samples were collected for 3 h prior to and 4 h following thyrotropin releasing hormone (TRH) administration, and were analyzed for growth hormone (GH) and prolactin (PRL) concentrations. Dry matter intake, body weight and milk yield and fat content were used to calculate net energy balance (NEB) of animals at each DPP sampling period. Mean plasma GH concentrations were greater (P less than .01) in selection vs control animals both before and after TRH administration, and decreased (P less than .01) with advancing lactation (30 greater than 90 greater than 200 DPP). However, NEB was not influenced by genetic merit, implying that observed differences in GH concentrations were not due to that trait. Plasma PRL concentrations were not affected by genetic merit or DPP, but were greater (P less than .01) in the second vs first lactation. Neither PRL or GH concentrations were affected by frequency of milking. The results support the contention that increased plasma GH concentrations are associated with selection for increased milk yield.     

Pharmacokinetics of phenylbutazone in mature Holstein bulls: steady-state kinetics after multiple oral dosing

Six mature Holstein bulls were given an 8-day course of phenylbutazone (PBZ) orally (loading dose, 12 mg of PBZ/kg of body weight and 7 maintenance doses of 6 mg of PBZ/kg, q 24 h). Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling. The harmonic mean +/- pseudo-SD of the biologic half-life of PBZ was 61.8 +/- 12.8 hours. The arithmetic mean +/- SEM of the total body clearance and apparent volume of distribution were 0.0021 +/- 0.0001 L/h/kg and 0.201 +/- 0.009 L/kg, respectively. The predicted mean minimal plasma concentration of PBZ with this dosage regimen was 75.06 +/- 4.05 micrograms/ml. The predicted minimal plasma drug concentration was compared with the observed minimal plasma drug concentration in another group of bulls treated with PBZ for at least 60 days. Sixteen mature Holstein bulls were given approximately 6 mg of PBZ/kg, PO, daily for various musculoskeletal disorders. The mean observed minimal plasma concentration of PBZ in the 16 bulls was 76.10 +/- 2.04 micrograms/ml, whereas the mean predicted minimal plasma concentration was 74.69 +/- 3.10 micrograms/ml. Dosages of 4 to 6 mg of PBZ/kg, q 24 h, or 10 to 14 mg of PBZ/kg, q 48 h, provided therapeutic plasma concentrations of PBZ with minimal steady-state concentrations between 50 and 70 micrograms/ml.     

Effects of clinical mastitis on reproductive and milk performance of Holstein cows in Morocco

The aim of this study was to determine the influence of clinical mastitis and time of first mastitis occurrence on reproductive and milk performance of Holstein cows. Data were collected in a dairy farm from 2008 to 2012 on 1725 cows, among which 464 cows with mastitis. To determine the influence of clinical mastitis on reproductive and milk performance, models included fixed effects of parity, calving season, calving year, and group (cows with and with no mastitis). To determine the effect of time of 1st mastitis occurrence on reproductive performance, the mastitic cows group was further reclassified into three groups: prior to 60 days, between 60 and 90 days and greater than 90 days postpartum. For milk performance, the mastitic cows group was divided into two groups: before and after peak milk yield. Clinical mastitis had significant effects on calving to first AI interval, milk yield, and fat yield, but a non-significant effect on days open, number of inseminations per conception, and milk fat percentage. Mastitic cows had a calving to first AI interval 6.1 days longer and 549.6 kg milk and 20.4 kg fat per 305 days of lactation lower than those with no mastitis. Time of 1st mastitis occurrence did not have any significant effect on reproductive performance. Further, milk and fat yields of cows diseased before peak milk yield were 506 kg and 23.9 kg, respectively, lower than those of cows affected after peak milk yield. Extra attention needs to be paid to mastitis during the early postpartum period.

     

ELOVL5基因遗传变异与中国荷斯坦奶牛乳质性状的关联分析及功能验证

采用测序的方法鉴定136头中国荷斯坦奶牛ELOVL5基因启动子区域的遗传多态性位点,通过统计学分析遗传多态性位点与乳质性状的关联性,并根据差异显著性多态性位点构建ELOVL5基因启动子双荧光素酶报告载体,检测不同基因型的启动子活性。结果表明:在奶牛ELOVL5基因启动子区域中发现了7个SNPs及1个单碱基缺失突变,其中SNP7g.-385C>G与尿素氮、校正奶量显著相关(P<0.05),单碱基缺失突变与牛奶中的体细胞数极显著相关(P<0.01)。双荧光素酶报告载体检测结果显示,缺失纯合基因型的启动子活性极显著高于野生型(P<0.01)。     

Pharmacokinetics and milk residues of butorphanol in dairy cows after single intravenous administration

The pharmacokinetics of butorphanol tartrate were investigated following intravenous administration of 0.25 mg/kg of body weight to six healthy non-lactating Jersey cows. Three lactating Holstein cows also received 0.045 mg of butorphanol/kg of body weight intravenously to determine the extent and duration of drug transfer into milk. A radioimmunoassay technique was used to measure butorphanol concentrations in plasma and milk. The disposition of butorphanol following intravenous administration was characterized by rapid and extensive distribution followed by a slower elimination phase. Apparent volume of distribution was 4.178 ± 1.145 (mean ± SD) I/kg, mean elimination half-life was 82 min, and clearance was 34.6 ± 7.7 ml/min/kg. Trace quantities of butorphanol were detected in the cow's milk for up to 36 h following administration. These pharmacokinetic data were compared with pharmaco-kinetic and pharmacodynamic data for butorphanol in other species and for three other potent opioids in related ruminant species.     

荷斯坦奶牛妊娠早期血浆差异蛋白质组学研究

采用二维凝胶电泳(2-DE)结合MADIL-TOF-TOF串联质谱法对荷斯坦奶牛妊娠早期血浆进行蛋白质组学分析鉴定,发现了6种差异蛋白在妊娠后表达量上调,分别是凝集素1前体、转甲状腺素蛋白前体、3,5-二碘水杨酸络合的牛血清白蛋白的晶体结构的A链、白蛋白、未命名蛋白产物及结合珠蛋白-25同源物1前体。对这6种蛋白在不同时期含量的变化趋势及可能引起每种蛋白含量变化的原因和在妊娠过程中的功能进行了分析。     

Natural antibodies in bovine milk and blood plasma: variability among cows, repeatability within cows, and relation between milk and plasma titers

Innate immunity plays an important role in preventing (barrier function) or combating infection (effector function). An important humoral component of innate immunity is formed by natural antibodies (NAb). The objectives of this study were to determine presence, variation among cows and repeatability within cows over time of total NAb titers directed to the pathogen-associated molecular patterns lipopolysaccharide, lipoteichoic acid (LTA) and peptidoglycan, and titers of NAb directed to the glycoprotein keyhole limpet hemocyanin in milk and plasma of individual cows. Furthermore in milk the antibody isotypes IgG1, IgG2, IgM and IgA binding LTA were analyzed. Ten milk and blood samples were obtained from each of 20 clinically healthy dairy cows from first to seventh parity during a period of 3 weeks. Total NAb binding lipopolysaccharide, LTA, peptidoglycan, and keyhole limpet hemocyanin were detected in milk and plasma, with titers considerably higher in plasma than in milk. Total NAb titers showed significant variation among cows, and repeatability within cows over time (ranging from 0.60 to 0.93). Titers of NAb in milk and plasma were positively correlated (correlation ranging from 0.69 to 0.91). Natural antibodies in milk binding LTA were of all 4 isotypes tested, although IgG2 was on average only present at low titers. All 4 isotypes in milk binding LTA also showed variation among cows, and repeatability within cows over time (ranging from 0.84 to 0.92). We conclude that NAb can be measured in a consistent and repeatable manner in bovine milk and blood plasma.