Subclinical ketosis (SCK) is defined as concentrations of β-hydroxybutyrate (BHBA) ≥ 1.2 to 1.4 mmol/L and it is considered a gateway condition for other metabolic and infectious disorders such as metritis, mastitis, clinical ketosis, and displaced abomasum. Reported prevalence rates range from 6.9 to 43% in the first 2 mo of lactation. However, there is a dearth of information on prevalence rates considering the diversity of European dairy farms. The objectives of this study were to (1) determine prevalence of SCK, (2) identify thresholds of BHBA, and (3) study their relationships with postpartum metritis, clinical ketosis, displaced abomasum, lameness, and mastitis in European dairy farms. From May to October 2011, a convenience sample of 528 dairy herds from Croatia, Germany, Hungary, Italy, Poland, Portugal, Serbia, Slovenia, Spain, and Turkey was studied. β-Hydroxybutyrate levels were measured in 5,884 cows with a handheld meter within 2 to 15 d in milk (DIM). On average, 11 cows were enrolled per farm and relevant information (e.g., DIM, postpartum diseases, herd size) was recorded. Using receiver operator characteristic curve analyses, blood BHBA thresholds were determined for the occurrence of metritis, mastitis, clinical ketosis, displaced abomasum, and lameness. Multivariate binary logistic regression models were built for each disease, considering cow as the experimental unit and herd as a random effect. Overall prevalence of SCK (i.e., blood BHBA ≥ 1.2 mmol/L) within 10 countries was 21.8%, ranging from 11.2 to 36.6%. Cows with SCK had 1.5, 9.5, and 5.0 times greater odds of developing metritis, clinical ketosis, and displaced abomasum, respectively. Multivariate binary logistic regression models demonstrated that cows with blood BHBA levels of ≥ 1.4, ≥ 1.1 and ≥ 1.7 mmol/L during 2 to 15 DIM had 1.7, 10.5, and 6.9 times greater odds of developing metritis, clinical ketosis, and displaced abomasum, respectively, compared with cows with lower BHBA blood levels. Interestingly, a postpartum blood BHBA threshold ≥ 1.1 mmol/L increased the odds for lameness in dairy cows 1.8 (95% confidence interval: 1.3 to 2.5) times. Overall, prevalence of SCK was high between 2 to 15 DIM and SCK increased the odds of metritis, clinical ketosis, lameness, and displaced abomasum in European dairy herds.

Numerous adjunct therapeutic agents have been investigated for the treatment or control of fat mobilization syndrome in periparturient dairy cows. The aim of this study was to determine the effects of multiple i.v. injections of 10% butaphosphan and 0.005% cyanocobalamin combination (Catosal, Bayer Animal Health, Leverkusen, Germany) between 1 and 2 wk antepartum (a.p.) on the metabolism and health of dairy cows. Forty-five late-gestation Holstein-Friesian cows (second pregnancy) were allocated randomly to 1 of 3 groups with 15 cows/group: group C6 (6 daily i.v. injections of butaphosphan at 10 mg/kg of body weight (BW) and cyanocobalamin at 5 microg/kg of BW in the last 2 wk of gestation); group C3 (3 daily i.v. injections of butaphosphan at 10 mg/kg of BW and cyanocobalamin at 5 microg/kg of BW in the last week of gestation); and group C0 (equivolume daily i.v. injections of 0.9% NaCl solution). Serum biochemical analysis was performed on jugular venous blood samples that were periodically obtained a.p. and postpartum (p.p.). Health status and milk production were monitored p.p. Serum cyanocobalamin concentration increased in groups C6 and C3 p.p. Multiple daily i.v. injections of Catosal before parturition increased p.p. glucose availability, as evaluated by p.p. serum glucose concentration, and decreased peripheral fat mobilization and ketone body formation, as evaluated by p.p. serum nonesterified fatty acid and beta-OH butyrate concentrations. The number of puerperal infections in the first 5 d after calving was decreased in group C6, relative to group C0. We conclude that multiple injections of Catosal during the close-up period have a beneficial effect on the metabolism of periparturient dairy cows. Our results are consistent with the hypothesis that high-producing dairy cows in early lactation may have a relative or actual deficiency of cyanocobalamin.

The primary aim was to investigate the effect of combined butafosfan and cyanocobalamin on liver metabolism in early lactating cows through mRNA expression measurements of genes encoding 31 enzymes and transport proteins of major metabolic processes in the liver using 16 multiparous early lactating dairy cows. The treatments included i.v. injection of 10 mL/100 kg of body weight combined butafosfan and cyanocobalamin (TG, n = 8) on 3 d consecutively at 25 ± 3 d in milk or injection with physiological saline solution similarly applied (CG, n = 8). Results include a higher daily milk production for TG cows (41.1 ± 0.9 kg, mean ± SEM) compared with CG cows (39.5 ± 0.7 kg). In plasma, the concentration of inorganic phosphorus was lower in the TG cows (1.25 ± 0.08 mmol/L) after the treatment than in the CG cows (1.33 ± 0.07 mmol/L). The plasma β-hydroxybutyrate concentration was 0.65 ± 0.13 mmol/L for all cows before the treatment, and remained unaffected post treatment. The unique result was that in the liver, the mRNA abundance of acyl-coenzyme A synthetase long-chain family member 1, involved in fatty acid oxidation and biosynthesis, was lower across time points after the treatment for TG compared with CG cows (17.5 ± 0.15 versus 18.1 ± 0.24 cycle threshold, log(2), respectively). In conclusion, certain effects of combined butafosfan and cyanocobalamin were observed on mRNA abundance of a gene in the liver of nonketotic early lactating cows.

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Citation of This Article AbstractThis study was conducted to assess the effects of different doses of butaphosphan-cyanocobalamin combination onbody condition score (BCS), betahydroxybutyrate (BHBA) and reproductive parameters in cows with subclinical ketosis (SCK). Holstein-Friesen cows (n=544) were checked for BHBA concentration. Cows with SCK (n=53, BHBA ranging from 1.00 to 3.00 mmol/L) were assigned randomly to receive saline (C0, n=18), 5 mL/100 kg BW (C5, n=18) or 10 mL/100 kg BW (C10, n=17) butaphosphan-cyanocobalamin combination. BHBA concentration was measured on d 0, 10, and 18 relative to treatment application. BCS was evaluated weekly until d 60 postpartum. For reproductive parameters cows were monitored until d 150 postpartum. The median reduction in blood BHBA concentrations was 28, 57, and 75% for C0, C5, and C10, respectively. NEFA and total bilirubin concentrations were significantly decreased in C10 group. The relative median change in BCS as compared to baseline was 17, 12, and 6% for C0, C5, and C10, respectively. Between d 15 and 25 postpartum uterine involution was completed in 44, 83, and 88% of cows in groups C0, C5, and C10, respectively. Interval from calving to first insemination in group C10 was shorter than control group. Overall pregnancy rate was not different among groups. In conclusion butaphosphan-cyanocobalamin combination decreased severity of hyperketonemia, stimulated uterine involution, shortened time to first insemination and increased pregnancy rate. Keywords: Beta hydroxybutyrate, Butaphosphan, Cyanocobalamin, Subclinical ketosis, Reproductive performance Subklinik Ketosisli Süt İneklerinde Farklı Dozlarda Butafosfan ve Siyanokobalamin Kombinasyonunun Etkisinin Değerlendirilmesi ÖzetBu çalışma, subklinik ketozisli (SCK) süt ineklerinde farklı dozlarda butafosfan-siyanokobalamin kombinasyonunun vücut kondisyon skoru (VKS), betahidroksibütirat (BHBA) ve reprodüktif parametreler üzerine etkilerini değerlendirmek amacıyla gerçekleştirildi. Holştayn-Frizyan inekler (n=544) BHBA yönünden kontrol edildi. SCK'li inekler (n=53, 1.00-3.00 mmol/L BHBA); 4 gün süresince günlük salin uygulanan (C0, n=18) ve canlı ağırlığa 5 mL/100 kg dozunda (C5, n=18) ya da canlı ağırlığa 10 mL/100 kg dozunda (C10, n=17) butafosfan-siyanokobalamin kombinasyonunun uygulandığı gruplara rastgele olarak ayrıldı. BHBA düzeyleri; 0, 10 ve 18. günlerde ölçüldü. VKS postpartum 60. güne kadar haftalık değerlendirildi. Reprodüktif parametreler için inekler doğum sonrası 150. güne kadar takip edildi. Kan BHBA düzeyinde medyan azalma C0, C5 ve C10 grubunda sırasıyla %28, %57 ve %75 olarak gerçekleşti. NEFA ve total bilirübin düzeyleri C10 grubunda anlamlı şekilde azaldı. VKS'un relatif medyan değişimi baseline ile karşılaştırıldığında C0, C5 ve C10 grubunda sırasıyla %17, %12 ve %6 olarak belirlendi. Postpartum 15 ve 25. günler arasında uterus involüsyonu C0, C5 ve C10 gruplarında sırasıyla %44, %83 ve %88 tamamlandı. C10 grubunda buzağılama ilk tohumlama aralığı kontrol grubundan daha kısaydı. Ortalama gebeli...

Many dairy cows experience a high incidence of health problems during the transition period (TP). The TP is an intermediate stage of various digestive, metabolic and reproductive functions which determine the general health status at the time of calving and during the first weeks postpartum. Negative energy balance due to increased energy demand at parturition and significantly reduced dry matter intake relative to demand is an important determinant. Consequently, substantial lipid mobilization from adipose tissue, increased oxidative stress and impaired immunity are associated with higher incidences of periparturient health problems including ketosis or subclinical ketosis (SCK), which have tremendous economic impact on dairy productivity. SCK is defined as the presence of increased blood ketone bodies (BHBA: betahydroxybutyric acid, acetone, acetoacetic acid) without clinical ketosis signs. Varying blood and milk cut-off values have been reported for BHBA concentrations defining SCK, but the most commonly accepted values are ≥ 1.2 mmol/L and ≥ 200 μmol/L respectively. This underestimated disease can impact dairy cow productivity through decreased milk production in the order of roughly 300 kg/lactation and increases the risk of metabolic and reproductive diseases such as displaced abomasum, retained placenta, metritis, mastitis, prolong oestrus interval and reduces conception rates. SCK also referred to as ‘profit robber or killer’ can cause productivity and economic losses of between $200-290 per dairy cow annually. Options for the control and prevention of SCK include controlled-release monensin capsules, and the injectable combination butaphosphan and cyanocobalamin and oral propylene glycol. SCK is easy to detect in early lactation using cow-side validated BHBA analysers with high specificity and sensitivity.

16 Calves were each infected with suspensions containing a mixture of approximately 230,000 Eimeria bovis and 70,000 E. zuernii oocysts, which resulted in detection of oocysts in faeces of 12 of 16 calves by day +14 after infection. On day +14 after infection calves were either treated (n = 8) with toltrazuril at 15 mg/kg body weight or with a placebo. Observations were made on the clinical condition, faecal score and liveweight of calves daily from one day post infection (pi) until 24 days pi when all calves were euthanised and examined post mortem. Samples were collected from ileum and colon for histological, immunohistochemical and gene expression studies. The study demonstrated an efficacy of toltrazuril for the treatment of E. bovis and E. zuernii infections in calves reaching 99 % (based on arithmetic mean oocyst counts in faeces) within three days of treatment and remaining at or above this level for six days. Toltrazuril did not have a significant effect on the pattern and extent of immune cellular infiltration in the mucosa of ileum and colon, but the expression of the genes coding IL-2, IL-10 and TNF-α in the ileum and TNF-α in the colon were elevated in calves treated with toltrazuril. Higher levels of oocyst shedding were significantly associated with lower expression of genes coding for IL-2, IL-10 and higher IP-10. It is concluded that toltrazuril is effective for the treatment of coccidiosis due to E. bovis and E. zuernii in calves and enables the development of a normal or enhanced immune response to infection.

The efficacy of toltrazuril treatment was assessed in two experiments in Polish swine herds. Experiment 1 included a toltrazuril treatment group, Group A (n = 410), and untreated control, Group B (n = 386). Time to sale in Group A was 108 days versus 120 days for Group B, with average body weights at sale of 114.2 kg and 108.8 kg, respectively (P < 0.05). In experiment 2, the health status and body weight gain of 238 piglets treated with toltrazuril (Group D) were compared to 235 untreated piglets (Group K). A similar difference was observed in average body weights of slaughtered animals, being on average 104 kg in Group D and 101 kg in Group K (P < 0.01). Animals from Group D were slaughtered 5 days earlier than animals from Group K (day 166 versus day 171). Data from clinical trials suggest treatment of coccidiosis with toltrazuril offering potential for improved animal welfare and yields, however this has remained unproven in field conditions in large swine production facilities. The present study confirms the efficacy of toltrazuril treatment when used in the field and the subsequent positive impact on time to weaning, time to market, and on weight gain at all time points.