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.     

Antibiotic residues in milk following bulbar subconjunctival injection of procaine penicillin G in dairy cows

OBJECTIVE: To determine whether, and at what time, penicillin enters milk at a concentration that is detectable following bulbar subconjunctival injection in lactating dairy cows. DESIGN: Randomized clinical trial. ANIMALS: 66 Holstein cows that were at least 2 weeks past calving and had not been treated with antibiotics in the preceding 30 days. PROCEDURE: Cows were randomly assigned to receive a treatment of 1 ml (300,000 units) procaine penicillin G by bulbar subconjunctival injection or remain untreated. Composite milk samples were collected immediately before treatment and 4, 10, 16, 22, 28, and 40 hours after treatment. Milk samples were tested by use of a commercial test for beta-lactam antibiotics. RESULTS: Among penicillin-treated cows, the first positive test results were observed 4 hours after treatment, and the last positive result was observed 22 hours after treatment. The percentages of positive test results before treatment and at 4, 10, 16, 22, 28, and 40 hours after treatment were 0, 9, 87, 42, 8, 0, and 0%, respectively. None of the untreated cows had positive test results for beta-lactam antibiotics at any sampling time. CONCLUSIONS AND CLINICAL RELEVANCE: Penicillin was detected in milk for up to 22 hours after a single subconjunctival injection of procaine penicillin G in cows. This result should be considered when recommending milk withholding periods following the administration of penicillin by this route in lactating dairy cows.     

头孢氨苄治疗奶牛乳房炎的效果及在牛奶中残留规律的研究

研究通过临床确诊患乳房炎的奶牛71头,采用头孢氨苄的4种不同用药方法进行治疗,用药后观察治疗效果及检测其残留规律。结果显示:肌注头孢氨苄、肌注头孢氨苄联合肌注普鲁卡因、静注头孢氨苄、静注头孢氨苄联合乳管注入普鲁卡因4种用药方案治疗奶牛乳房炎的有效率为75%～88.9%,平均有效率为81.8%;治愈率在65%～83.3%之间,平均治愈率为74.6%。通过检测,单独用药和联合用药对残留规律的影响不大,二者差异不显著。单独肌肉注射和联合肌肉注射普鲁卡因的弃奶期分别为59、58h(2.5d);单独静脉注射、联合乳管注入普鲁卡因的弃奶期分别为56、52h,4种用药方法的弃奶期比标准规定的2d延长了12h。     

Farming practices in Sweden related to feeding milk and colostrum from cows treated with antimicrobials to dairy calves

Background

Milk produced by cows in receipt of antimicrobial therapy may contain antimicrobial residues. Such antimicrobial-containing waste milk must be withdrawn from human consumption and is therefore sometimes used as calf feed. Unfortunately, this approach might promote selection of antimicrobial resistant bacteria in the calves’ intestinal microbiota. The objectives of this study were therefore to obtain an overview of waste milk feeding practices on Swedish dairy farms and to investigate if these practices were associated with certain farm characteristics. A representative group of 457 Swedish dairy farmers participated in a web-based survey with questions about the use of colostrum and milk from cows treated with antimicrobials at dry off or during lactation, respectively, as calf feed.

Results

Colostrum (milk from the first milking after calving) and transition milk (milk from the second milking to the fourth day after calving) from cows treated with antimicrobials at dry off was fed to calves on 89% and 85% of the farms in the study, respectively. When antimicrobial therapy was given to cows during lactation, 56% of the farms fed milk that was produced during the course of treatment to calves, whereas milk that was produced during the subsequent withdrawal period was fed to calves on 79% of the farms. Surveyed farmers were less prone to feed such milk if the antimicrobial therapy was due to mastitis than other infections. In Sweden, a majority of antimicrobial treatments during lactation are systemic administration of benzylpenicillin and thus, the bulk of waste milk in Sweden is likely to contain residues of this drug. Feeding waste milk to calves was more common on non-organic farms, and on farms located in Southern Sweden, and was less common on farms with cows housed in cold free stalls barns.

Conclusions

Waste milk that may contain antimicrobial residues is, at least occasionally, used as feed for calves on a majority of surveyed Swedish dairy farms. Future work should focus on the effect of waste milk feeding on the occurrence of antimicrobial resistant bacteria in the calves’ intestinal microbiota.     

Normal and disturbed milk ejection in dairy cows

More than 80% of the milk stored in the udder, i.e. the alveolar fraction, only available after milk ejection is induced by the release of oxytocin and myoepithelial contraction. Milk ejection is induced by tactile teat stimulation, either manually or by the milking machine. The time from the start of a tactile stimulation until the occurrence of milk ejection spans from 40 s up to more than 2 min and increases with decreasing degree of udder filling. Therefore, cows need a longer pre-stimulation in late stages of lactation or if the milking is performed shortly after the previous milking whereas in full udders, pre-stimulation is less important. Milk ejection can be disturbed under several conditions, for example, during milking in unfamiliar surroundings or for several weeks after parturition in many primiparous cows. We found that a disturbed milk ejection is due to a reduced release or complete absence of oxytocin from the pituitary. During milkings with disturbed milk ejection in unfamiliar surroundings, the concentrations of cortisol and beta-endorphin were elevated. While exogenous glucocorticoids could not induce the disturbance, morphine caused inhibition of oxytocin release during milking. However, spontaneously occurring disturbance of milk ejection could not be abolished by the opioid-antagonist naloxone. On the other hand, severity of disturbed milk ejection and coping capacity towards novel milking environment was inversely related to the cortisol release in response to ACTH, i.e. adrenal cortex activity. Therefore, the susceptibility of individual cows to the inhibition of oxytocin release and milk ejection could be predicted by an ACTH challenge test.     

Methane production from thermophilic co‐digestion of dairy manure and waste milk obtained from therapeutically treated cows

Methane production from co‐digestion of dairy manure and waste milk, milk from cows treated with antibiotics for mastitis, was tested in a 2 × 4 factorial design. Four different waste milk percentages (w/w): 0% (SM), 10% (SMWM10), 20% (SMWM20) and 30% (SMWM30), were tested with two slurry percentages (w/w): 50% (A) and 25% (B) and the rest being manure at 55°C for 12 days in batch digesters. The results analyzed using a Gompertz model showed SMWM10 produced the highest methane production potential (P_m)/g volatile solids added followed by SM in both A and B. This P_m of SMWM10 in A and B was statistically non‐significant (P > 0.05). More than 96% of cefazolin‐resistant bacteria and 100% of multi‐drug‐resistant bacteria reductions were observed in all the treatments. Inclusion of waste milk at 10% in single stage digester enhances the methane production from dairy manure and could offer added benefit of waste milk treatment and disposal.     

Non-additive effects on milk production in Czech dairy cows

Crossbreeding effects on milk production traits of Czech dual‐purpose and dairy cattle breeds were estimated. Nearly 370 000 cows with known gene proportions from Czech Pied, Ayrshire or Holstein cattle were selected from the national milk recording data base. Single‐trait animal models were calculated for milk, fat and protein yield, fat and protein content. The model of Dickerson including additive, additive maternal, heterotic and recombination effects was used for the part of the animal model describing the crossbreeding effects in all calculations. For milk yield, the additive genetic effect (defined as deviation from Czech Pied cattle) was 850–900 kg for Holstein and 240–480 kg for Ayrshire. The maternal effects were low and negative. Low significant positive heterotic effects were observed being up to approximately 100 kg for Czech Pied × Holstein. The recombination effects were negative and statistically significant for Czech Pied × Holstein. The results for fat and protein yield were similar to the results for milk yield. For fat and protein content, nearly no statistically significant crossbreeding effects were found.     

Effect of lameness on milk yield in dairy cows

OBJECTIVE: To examine the relationship between lameness and milk yield in dairy cows. DESIGN: Cohort study. ANIMALS: 531 dairy cows. PROCEDURE: Cows affected with lameness were classified into 1 of 3 groups on the basis of type of diseases or lesions observed, including interdigital phlegmon (foot rot), papillomatous digital dermatitis (foot warts), or claw lesions. Cows not affected with lameness were classified as healthy. From Dairy Herd Improvement Association records, 305-day mature equivalent milk yield data were collected at the end of lactation or when the cow left the herd. Milk yield was compared between cows affected with lameness and healthy cows. RESULTS: 167 (31%) cows were affected with lameness during lactation. Lame cows had claw lesions (60%), papillomatous digital dermatitis (31%), or interdigital phlegmon (9%). Milk yield in lame cows with interdigital phlegmon (mean, 17,122 lb) was significantly less, compared with healthy cows (19,007 lb). CONCLUSIONS AND CLINICAL RELEVANCE: In this herd, interdigital phlegmon was associated with a 10% decrease in milk production. Lame cows with claw lesions or papillomatous digital dermatitis produced less milk than healthy cows, but the difference was not significant.     

Oestrus detection in dairy cows by milk temperature measurement

The milk and body temperatures of 15 cows were monitored twice daily at milking times, over a total of 30 oestrous periods. The best determination of oestrus was based on a temperature rise of at least 0.2 degree C over the corresponding mean temperature of the three preceding days. This resulted in 72 +/- 16 per cent of oestruses, predicted by serial progesterone assays, being successfully detected by serial progesterone assays, being successfully detected and 11 +/- 3 per cent of false positives. The variable extent of the temperature rise at oestrus and the large daily fluctuations in temperature for individual cows, resulted in a moderate oestrus detection rate accompanied by an unacceptable level of false positives.     

奶牛乳房炎无乳链球菌的分离及PCR鉴定

利用THB(Todd-Hewitt Broth)固体培养基和色素试验培养基选择培养无乳链球菌,参照GenBank中无乳链球菌参考菌株(Accession:AF015927.1、JQ289582.1)16SrRNA和种属特异性基因cfb(CAMP因子)序列设计引物,对奶样中分离的12株疑似无乳链球菌进行鉴定。结果显示,经PCR扩增后,被检测的12株细菌均可扩增出预期大小的16S rRNA基因序列,而12株中有8株可以扩增出预期大小的cfb基因序列,条带单一,特异性好。序列BLAST显示,12株菌的16S rRNA基因序列与NCBI上报道的无乳链球菌相应序列高度同源(>99.0%),各分离菌株间的16S rRNA基因序列也高度同源(99.0%～100.0%);cfb基因序列与NCBI上已报道的无乳链球菌相应序列具有高度同源性(>99.0%),各菌株间cfb基因序列也高度同源(100.0%)。经选择培养与PCR鉴定结果可以确定12株疑似菌株中有8株为无乳链球菌。     

Acute phase proteins in serum and milk from dairy cows with clinical mastitis

The serum concentrations of haptoglobin, serum amyloid A and alpha1 acid glycoprotein were determined in serum collected from healthy dairy cows and cows with clinical mastitis, graded as mild (clots in milk) or moderate (clots in milk and visible signs of inflammation in the mammary gland/s) to assess their relative diagnostic value in detecting the disease. The concentrations of haptoglobin and serum amyloid A were also measured in milk collected from infected and uninfected quarters. The concentrations of haptoglobin and serum amyloid A were higher in the serum and milk from the cows with mild or moderate mastitis. The diagnostic value of haptoglobin in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 82 per cent and 94 per cent respectively with serum and 86 per cent and 100 per cent with milk. The diagnostic value of serum amyloid A in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 83 per cent and 90 per cent with serum and 93 per cent and 100 per cent with milk. The diagnostic value of serum alpha1 acid glycoprotein in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 62 per cent and 91 per cent.     

Determination of cloxacillin residues in dairy cows after intramammary administration

The aim of this study was to perform a comparative analysis of the characteristics of cloxacillin (CLO) (MRL of withdrawal in bovine milk is 30 ng/g) after a single intramammary (IMM) dose in the dry period (DP) and lactation (LP), and to establish a high‐performance liquid chromatography (HPLC) analytical method for CLO detection in milk. The research was conducted on a group of 10 cows in DP and 10 in LP. A single dose of 600 mg of CLO was administrated by the IMM route for a single quarter in DP and 500 mg for a single quarter in LP. CLO concentration was analyzed by HPLC. CLO was monitored at a wavelength of 206 nm. Pharmacokinetic calculations were performed using Phoenix^® WinNonlin^® 6.4 software. The calibration curve was linear over the range of 13.03–28 019.00 ng/g with the coefficient of determination R² > 0.999. CLO withdrawal in both the LP and DP group had a biphasic nature. The total CLO elimination in the DP and LP group was reached after 36 and 6.5 days, respectively. A quantitative and confirmatory method for the determination of CLO in fresh milk has been established. We have confirmed that the withdrawal of CLO in the DP group is not a linear process and has a stepwise character.     

Ketosis treatment and milk yield in dairy cows related to milk acetoacetate levels

Milk yield and milk acetoacetate (M-acac) were measured weekly for the first 6 weeks of lactation in 5 herds with a ketosis problem. Ketosis treatments and the corresponding ketotest score, were also recorded. The treatment rate was highest 7-16 days after calving. Most of these early cases were associated with low ketone levels in milk, whereas the treatment rate for cows with high ketone levels was highest 17-31 days after calving. Nearly half of the treated cows were low-ketone animals. They were classified as ketosis cases in the cow health card records, although probably suffering from other post partum disturbances in many instances. About 40% of the cows with high ketone levels recovered spontaneously. Reduction in milk yield associated with peak M-acac levels was transient and moderate. It was concluded that health card statistics overestimates the severity of the ketosis problem in Norway.     

检测奶牛乳汁孕酮的免疫生物传感器优化

为了完善已建立的孕酮免疫生物传感器的检测性能,本试验应用碳化二亚胺法将11α-羟基孕酮半琥珀酸和OVA制备成孕酮完全抗原,其浓度达0.6 mg/m L。在此基础上建立了以乳汁为基质的孕酮生物传感器的标准曲线(y=-4.9461x+8.7982,R2=0.993 2),进一步确立了检测乳汁孕酮的线性范围为0.31 ng/m L~50ng/m L,检测限为0.31 ng/m L,灵敏度为0.15 ng/m L,而且孕酮与皮质酮、皮质醇、雄烯二酮的免疫交叉反应较低,表明特异性较好。批内、批间变异系数分别为7.7%和7.5%,回收率为95.8%~115.7%,生物传感器稳定性在4℃保存4 d。该优化的奶牛乳汁孕酮免疫生物传感器的性能参数符合规定的标准,为检测妊娠、乏情和繁殖障碍疾病的奶牛乳汁孕酮含量提供了工具。