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Background: Milk fever (MF), a metabolic disorder in dairy cows characterized by low blood calcium concentrations postpartum, is well-recognized clinically. However, comprehensive data on the alteration of metabolites associated with this condition remains sparse., Hypothesis: Delineate serum metabolite profiles and metabolic pathways preceding, coinciding with, and after the onset of MF., Animals: Twenty-six cows, including 20 healthy cows and 6 cows initially affected by MF. Because of culling, the number of MF-affected cows decreased to 4 at MF week, +4 weeks, and +8 weeks postpartum., Methods: A nested case-control longitudinal study was conducted, with blood samples collected at -8 and -4 weeks prepartum, MF week, and +4 and +8 weeks postpartum. Serum analysis utilized direct injection/liquid chromatography/tandem mass spectrometry (DI/LC/MS/MS) techniques., Results: Key findings included the identification of diverse metabolites such as hexose, amino acids, phosphatidylcholines, lysophosphatidylcholines, and sphingomyelin, which varied between studied groups (P < .05). The most marked metabolic alterations were observed 4 weeks prepartum. In total, 42, 56, 38, 29, and 24 metabolites distinguished the MF group at the respective time points (P < .05). Additionally, 33 metabolic pathways, including amino acid, antioxidant metabolism, fatty acid degradation, and carbohydrate processing, were impacted (P < .05)., Conclusions and Clinical Importance: Metabolic disruptions in dairy cows begin several weeks before the clinical manifestation of MF and persist up to 8 weeks postpartum. These findings emphasize the complexity of MF, extending beyond only hypocalcemia and indicate the necessity for preemptive monitoring in dairy herd management., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Milk fever is a metabolic disorder that predominantly affects dairy animals during the periparturient period and within four weeks of calving. Milk fever is primarily attributed to a decrease in the animal's serum Ca 2+ levels. Clinical milk fever occurs when Ca 2+ concentration drops below 1.5 mM (6 mg/dL). Without prompt intervention, clinical milk fever leads to noticeable physical symptoms and health complications including coma and fatality. Subclinical milk fever is characterized by Ca 2+ levels between 1.5 and 2.12 mM (6-8.48 mg/dL). Approximately 50% of multiparous dairy cows suffer from subclinical milk fever during the transition to lactation. The economic impact of milk fever, both direct and indirect, is substantial, posing challenges for farmers. To address this issue, we developed a low-cost electrochemical sensor that can measure bovine serum calcium levels on-site, providing an opportunity for early detection of subclinical and clinical milk fever and early intervention. This calcium sensor is a scalable solid contact ion sensing platform that incorporates a polymeric calcium-selective membrane and ionic liquid-based reference membrane into laser-induced graphene (LIG) electrodes. Our sensing platform demonstrates a sensitivity close to the theoretical Nernstian value (29.6 mV/dec) with a limit of detection of 15.6 μM and selectivity against the species in bovine serum. Moreover, our sensor can detect Ca 2+ in bovine serum with 91% recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Osteoprotegerin (OPG) inhibits osteoclast (OC) differentiation. TRAP5b (tartrate-resistant acid phosphatase 5b) secreted by OCs reflects the numbers of mature OCs. This study assessed these OC-related markers around parturition in cows of different parities and in cows with milk fever (MF). The blood OPG and TRAP5b concentrations, as well as the ratio of OPG to TRAP5b (O/T), were measured beginning 3 weeks before (-21 d) and over a few days after calving in 49 Holstein Friesian cows at first (n = 8), second (n = 17), third (n = 12), and fourth or greater (n = 12) parities. The ratio of O/T at -21 d to O/T at calving (PreCOT) was also calculated. In the third and greater parities, seven cows developed MF (non-MF, n = 17). Regardless of the development of MF, the serum OPG started to decline in the last week of gestation only in the cows entering the second lactation, while the blood TRAP5b increased at calving in all cows. O/T decreased toward parturition only in multiparous cows. The decrease in O/T at caving was less pronounced in MF cows. PreCOT was negatively correlated with lactation number only in multiparous cows (n = 41, ρ = -0.50, P < .01). This study implied that OC differentiation toward calving was tapered in cows with advanced parities, and these indexes predict the risk of MF., Competing Interests: Declaration of Competing Interest The authors declare no conflicts on interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Milk fever (MF) is a metabolic disease in dairy cows around parturition. The clinical lead sign is muscular paresis leading in severe cases to paralysis of the affected animal. Multiparturient animals of high performing dairy breeds are most likely to be affected and have a high probability of recurrence. An acute drop in blood calcium levels causes the disease when the demand for calcium at the onset of lactation exceeds the ability to replete blood calcium levels through mobilization from bone and intestinal uptake. With the understanding of the underlying mechanism, calcium supply management and vitamin D supplementation became prime candidates for MF prevention and therapy. Several strategies have been developed for MF prevention. Application of the active form of Vitamin D, 1,25(OH) 2 D 3 , was found to prevent MF effectively. In order to prevent a delayed hypocalcemia, which was occasionally seen after stopping the treatment with 1,25(OH) 2 D 3, a new approach was chosen by applying Solanum glaucophyllum extract (SGE), which contains 1,25(OH) 2 D 3 -glycosides, as instant-release (irSGE) in combination with slow-release (srSGE) tablets. In a first study, non-lactating cows were treated with a single bolus of either synthetic 1,25(OH) 2 D 3 , irSGE, or srSGE and the results were compared to a control group without treatment. Blood serum levels of 1,25(OH) 2 D 3 (1,25D), calcium (Ca), phosphate (P) and magnesium (Mg) were followed for 11days and the area under the curve (AUC) was calculated. Calcium and phosphate excretion in urine were determined during 15days. While serum concentration of 1,25(OH) 2 D 3 was back to pre-treatment level in the irSGE, srSGE and 1,25(OH) 2 D 3 treated group within 3days, calcium and phosphate levels remained elevated for up to 9days. AUC of serum 1,25(OH) 2 D 3 was 2.89 (1,25D), 3.13 (irSGE) and 4.21 (srSGE) times higher than control. Serum calcium levels were 1.07 * (for 1.25D); 1.08 * (for irSGE) and 1.12 * (for srSGE) times higher than control. Serum phosphate levels were 1.20 * (for 1,25D); 1.30 * (for irSGE) and 1.41 * (for srSGE) times higher than control, with * p<0.05. In a second field study calving cows treated with one bolus containing ir- and sr- tablets of SGE were compared to an untreated control group and to a group treated with 4 boli of commercial calcium salts. As a result, calcium serum levels increased (+19% compared to baseline) around calving after treatment with the single bolus of SGE. The single bolus of SGE lead also to an increase of serum phosphate (+31% compared to baseline). These calcium and phosphate increases were statistically significant (p<0.001) 0-24h after calving compared to the control group and to the group treated with calcium salts. The sample size of the study was too small to draw a conclusion on the effect on MF prevention. In conclusion, application of a single bolus of a SGE extract lead to an increase of serum calcium and phosphate for up to 9days and may thus have the potential to prevent a hypocalcemia and -phosphatemia, an important cause for clinical milk fever., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Subclinical hypocalcemia is considered a gateway disease that increases susceptibility to other metabolic and infectious diseases in transition dairy cows. In the absence of a cow-side test, however, it is difficult to identify hypocalcemic cows. The objective of this study was to evaluate ear skin temperature as a diagnostic predictor of serum calcium concentration. We conducted a cross-sectional study on 7 commercial dairy farms, involving 251 cows 0 to 48h after calving. Skin temperature of the ears (STEar) was scored manually by palpating both ears. An infrared thermometer was used to measure ear temperature, skin temperature on the coxal tuber (STCox), and ambient temperature. Rectal temperature was measured using a digital thermometer. A blood sample was drawn to determine serum calcium concentration. Hypocalcemia was defined as serum calcium below 2.0mmol/L, irrespective of clinical symptoms. Serum calcium concentration <2.0mmol/L in connection with clinical symptoms was defined as clinical milk fever; serum calcium concentration <2.0mmol/L without clinical symptoms was defined as subclinical hypocalcemia. Multivariate analysis using the GENLINMIXED procedure and receiver operating characteristic analysis were performed to evaluate whether serum calcium concentration could be predicted using ear temperature and other temperature estimates. The prevalence of hypocalcemia was 3.3, 27.3, 32.8, and 69.6% for cows in first, second, third, and fourth or greater lactation, respectively. None of the cows in first and second lactation had clinical milk fever. The prevalence of clinical milk fever was 6.0 and 20.3% for cows in their third and fourth or greater lactation, respectively. A decrease in ear temperature of 0.39°C [95% confidence interval (CI): 0.25-0.54] was associated with a decrease of 0.1mmol/L in serum calcium concentration. Ambient temperature, however, was a major confounder for ear temperature. With an increase in ambient temperature of 1°C, STEar rose by 0.78°C (95% CI: 0.67-0.90). Hypothermia was more pronounced in clinical milk fever (median 21.8°C; interquartile range 14.7-27.0°C) compared with subclinical hypocalcemia (median 27.6°C, interquartile range 22.1-30.8°C). All temperature estimates had only accurate test characteristics based on their area under the curve for prediction of subclinical hypocalcemia (area under the curve for STEar, STCox, and rectal temperature were 0.641, 0.668, and 0.606, respectively) when cows with clinical milk fever were excluded. Although ear temperature has been associated with serum calcium concentration, ear temperature cannot be recommended for diagnosis of subclinical hypocalcemia., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The association between blood calcium levels and electrocardiographic variables was compared in 137 normal parturient and 36 peripartum recumbent Holstein cows to determine whether hypocalcemia in peripartum dairy cows can be rapidly diagnosed using electrocardiograph. Inverse of STc (ST peak interval/SS interval(0.5)) and blood ionized calcium or serum calcium concentrations were strongly correlated, and both correlation coefficients were 0.81 (P<0.001). The 95% prediction interval indicated that cows with STc >0.385 ± 0.001 sec are very likely to be hypocalcemic (blood ionized or serum calcium concentrations of <0.9 mmol/l or <7.5 mg/dl, respectively). These findings indicate that hypocalcemia in parturient cows can be non-invasively estimated using the STc.

Dairy cows may suffer events of hypocalcemia and hypomagnesemia, commonly known as milk fever and tetany. Milk fever is characterized by hypocalcemia at parturition as a consequence of a sudden increase in Ca demand and an unavoidable delay in Ca metabolism adaptation. Tetany is due to impaired Mg absorption from the rumen that cannot be compensated by absorptive or excretory adaptation, resulting in a net nutritional shortage of Mg and culminating in hypomagnesemia. Prevention strategies require triggering the activation of Ca gastrointestinal absorption and avoiding factors limiting ruminal Mg absorption., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Subclinical hypocalcemia may affect half of all multiparous cows, and clinical hypocalcemia or milk fever affects approximately 5% of dairy cows each year. This disorder of calcium homeostasis can be induced by several dietary factors. Recent studies implicate high dietary potassium and high dietary cation-anion difference (DCAD) with increased risk of milk fever. The hypothesis tested in this study was that high-DCAD diets fed to prepartum cows reduce tissue sensitivity to parathyroid hormone (PTH), inducing a pseudohypoparathyroid state that diminishes calcium homeostatic responses. Multiparous Jersey cows were fed low- or high-DCAD diets in late gestation, creating a compensated metabolic alkalosis in the high-DCAD cows and a compensated metabolic acidosis in the low-DCAD cows. They then received synthetic PTH injections at 3-h intervals for 48 h. Parathyroid hormone is expected to cause an increase in plasma calcium by increasing renal production of 1,25-dihydroxyvitamin D and increasing bone calcium resorption. Plasma calcium concentration increased at a significantly lower rate in cows fed the high-DCAD diet. Cows fed the high-DCAD diet also produced significantly less 1,25-dihydroxyvitamin D in response to the PTH injections than cows fed the low-DCAD diet. Serum concentrations of the bone resorption marker carboxyterminal telopeptide of type I collagen were numerically lower in cows fed the high-DCAD diet but this difference was not statistically significant. These data provide direct evidence that high-DCAD diets reduce tissue sensitivity to PTH. The metabolic alkalosis associated with high-DCAD diets likely induces a state of pseudohypoparathyroidism in some dairy cows at the onset of lactation, resulting in hypocalcemia and milk fever., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Milk fever (MF) is a common calcium metabolism disorder in perinatal cows. Currently, information regarding the detailed metabolism in cows suffering from MF is scant., Objective: The purpose was to study the metabolic profiling of serum samples from cows with MF in comparison to control cows, and thereby exploring other underlying pathological mechanisms of this disease., Animals and Methods: In the current study, we compared the serum metabolomic profile of dairy cows with MF (n = 8) to that of healthy dairy cows (n = 24) using a 500-MHz digital (1)H-nuclear magnetic resonance ((1)H-NMR) spectrometer. Based on their clinical presentation and serum calcium concentration, cows were assigned either to the control group (no MF symptoms and serum calcium concentration >2.5 mmol/L) or to the MF group (MF symptoms and serum calcium concentration <1.4 mmol/L). For statistical analysis, a one-way analysis of variance was performed., Results: We identified differences regarding nine metabolites between the two groups, among which glucose, alanine, glycerol, phosphocreatine, and gamma-aminobutyrate decreased, and β-hydroxybutyrate, acetone, pyruvate, and lysine increased in cows with MF. Most of these were carbohydrates and amino acids involved in various energy metabolism pathways., Conclusion: The different metabolites in cows with MF reflected the pathological features of negative energy balance and fat mobilization, suggesting that MF is associated with altered energy metabolism., Clinical Importance: The (1)H-NMR spectroscopy can be used to understand the pathogenesis of MF and identify biomarkers of the disease.

Objective: Frequent occurrence of parturient paresis (milk fever [MF]) and a partly unsatisfactory treatment success raises the question as to whether in addition to the known causes, other factors influence the incidence and success of MF treatment. Trace elements, including selenium (Se), are involved in bone metabolism, however, there is little knowledge regarding the influence of Se on MF development. The aim of this study was to analyse the concentrations of Se and the statistical relationships to parameters associated with Se influence in downer cows., Material and Methods: A total of 195 Simmental cows, downer cows and clinically healthy control animals were divided into five groups: a) control group (CG, n = 21), b) all cows with MF (n = 174), c) MF cows without additional diseases (n = 145), d) cows with MF and mastitis (n = 10) and e) cows with MF and retained placenta or endometritis (n = 19). Se, calcium (Ca), inorganic phosphate (Pi), tumour necrosis factor α (TNFα), haptoglobin (Hp), antioxidants (Trolox Equivalent Antioxidative Capacity: TEAC) and further metabolic parameters were analysed in the blood serum., Results: The serum concentrations of Se, Ca, Pi and TEAC were lower in groups b) to e), whereas Hp was higher than in the CG (p ≤ 0.05). Se was positively correlated with Pi in the CG, in groups b) and c) with Ca, Pi, K and Mg and in group c) with Hp (p ≤ 0.05). Both Ca and Pi were significantly lower in group c) compared to group d) (p ≤ 0.05). TNFα was increased in groups b) and c) compared to group a) and correlated with Se in group e) (p ≤ 0.05). Alkaline phosphatase activity in groups b) and e) was lower than in the CG and correlated with Se in the CG and group b) (p ≤ 0.05)., Conclusion: These results, in agreement with the literature data, support the hypothesis that Se could be directly involved in bone metabolism and therefore in the pathogenesis of MF. Se acts via cytokines on Ca mobilization from bone. The concentrations of Hp and TEAC support this interpretation. Therefore, control of the Se status and Se supplementation of cows should be included in the prevention and advanced therapy of MF.

Objective: The aim of this study was to analyse the concentrations of Zn and Fe as well as their relationships to metabolic parameters in milk fever cows., Material and Methods: A total of 195 Simmental cows, downer cows and clinically healthy control animals were divided into five groups: a) control group (CG, n = 21), b) all cows with milk fever (MF) (n = 174), c) MF cows without additional diseases (n = 145), d) cows with MF and mastitis (n = 10) and e) cows with retained placenta or endometritis (n = 19). Selenium (Se), zinc (Zn), iron (Fe), calcium (Ca), inorganic phosphorus (Pi), tumour necrosis factor α (TNFα), haptoglobin (Hp), antioxidants (Trolox Equivalent Antioxidative Capacity: TEAC), non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), bilirubin, urea, creatinine, glucose, cholesterol, gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) were analysed in the blood serum., Results: The concentrations of Zn, Fe, Ca, Pi and TEAC were lower in groups b) to e) whereas Hp was higher than in the CG (p ≤ 0.05). In group c), lower Ca and Pi concentrations were found when compared to groups d) and e) (p ≤ 0.05). In group e), Zn concentrations were significantly lower than in group c) (p ≤ 0.05). Zn was negatively correlated with K (CG) and positively correlated with TEAC, Cu, Mn and Fe (groups b and c) and with Mn (group e) (p ≤ 0.05). Fe was positively correlated with Ca (group c), Pi (group c), K (groups b and c) and Mg (groups b-d) as well as with Zn, Cu and Se (groups b and c) (p ≤ 0.05). In groups b) and c), TNFα was increased and negatively correlated with Fe (p ≤ 0.05). AP activity in groups b) and e) was lower than in the CG (p ≤ 0.05)., Conclusion: These results and literature data support the hypothesis that Zn and Fe could be engaged in bone metabolism and be involved in the pathogenesis of MF. The concentrations of Hp and TEAC support this interpretation. Control of the Zn and Fe status of cows and Zn supplementation should be included in the prevention and advanced therapy of MF.

Although a molecular diagnostic assay using clinically accessible tissue, such as blood, would facilitate evaluation of disease conditions in humans and animals, little information exists on microarray-based gene expression profiling of circulating leukocytes from clinically hypocalcemic cows. Therefore, peripheral blood mononuclear cells from dairy cows with experimentally induced hypocalcemia or spontaneous milk fever were subjected to oligo-microarray analysis to identify specific biomarker genes. In experimental hypocalcemia induced by a 4-h infusion of 10% disodium EDTA (n=4), 32 genes were significantly up- or downregulated compared with control treatment (4-h infusion of 11% calcium EDTA; n=4). In cows with milk fever (n=8), 98 genes were expressed differentially (either up- or downregulated) compared with healthy parturient cows (n=5). From these data, the following 5 genes were selected as being strongly related to both experimental hypocalcemia and milk fever: protein kinase (cAMP-dependent, catalytic) inhibitor β (PKIB); DNA-damage-inducible transcript 4 (DDIT4); period homolog 1 (PER1); NUAK family, SNF1-like kinase, 1 (NUAK1); and expressed sequence tag (BI537947). Another gene (neuroendocrine secretory protein 55, NESP55) was also determined to be specific for milk fever, independently of hypocalcemia. The mRNA expression of these 6 genes in milk fever cases was verified by quantitative real-time reverse-transcription PCR and was significantly different compared with their expression in healthy parturient cows. In the present study, the selected genes appeared to be candidate biomarkers of milk fever because the continuous interactions between blood cells and the entire body suggest that subtle intracellular changes occur in association with disease. However, before any genomic biomarkers are incorporated into clinical evaluation of the disease, the effect of hypocalcemia on the mRNA expression of these genes in the tissues that regulate calcium homeostasis in dairy cows should be determined., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The monoamine serotonin (5-hydroxytryptamine; 5-HT) has been described as a homeostatic regulator of lactation. Recently, our laboratory determined that 5-HT is involved in the regulation of calcium and glucose homeostasis during the transition period in rodents. More specifically, we demonstrate that 5-HT is responsible for calcium mobilization from bone and upregulation of hepatic gluconeogenic enzymes and mammary gland glucose transporters. Our objective was to investigate the correlation between circulating 5-HT concentrations and circulating ionized calcium, parathyroid hormone-related protein (PTHrP), and glucose concentrations on d 1 postpartum. We also investigated the correlation between circulating 5-HT and milk fever and ketosis incidence and severity in multiparous Holstein cows at the onset of lactation. Blood samples were collected from 42 multiparous cows on d 1 of lactation and analyzed for 5-HT, calcium, glucose, and PTHrP. Milk fever (determined subjectively for each cow on d 1 postpartum) and ketosis incidence and severity (scale 1 to 4, determined objectively for each cow during the first 10 d postpartum) were recorded for all animals. Serum 5-HT was positively correlated with serum calcium and with plasma PTHrP (r>0.37). Serum 5-HT was negatively correlated with milk fever incidence and with ketosis severity (most severe ketosis incidence recorded during the first 10 d postpartum; r<-0.33). Serum calcium and plasma glucose concentrations were negatively correlated with milk fever and ketosis severity, respectively (r<-0.39). These data indicate that 5-HT potentially plays a role in the regulation of calcium and glucose homeostasis during the transition period in cattle, which we previously demonstrated in rodents. Increased circulating concentrations of 5-HT might decrease milk fever at the onset of lactation and ketosis severity during the first 10 d postpartum in dairy cows. Understanding this physiological axis could help describe the underlying mechanisms associated with these periparturient metabolic disorders in dairy cows., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Milk fever, a metabolic disease of dairy cattle, is associated with perturbations of calcium homeostasis, the pathogenesis of which is not yet completely understood., Objective: The aim of this study was to investigate plasma concentrations of calcitonin gene-related peptide and selected minerals and metabolites in periparturient cows with and without milk fever., Methods: Plasma concentrations of calcitonin gene-related peptide, as well as calcium, phosphate, magnesium, iron, glucose, lactate, and cortisol, were determined in multiple plasma samples from Jersey cows with and without spontaneous milk fever., Results: Cows affected by milk fever (n = 5) had lower concentrations of calcitonin gene-related peptide (P = .038) and inorganic phosphate (P < .001) in plasma than did the controls (n = 5). Also, these cows tended to have lower calcium concentrations (P = .071). Magnesium, iron, lactate, glucose, and cortisol concentrations were comparable between both groups of cows (P > .10). Around the day of calving, plasma concentrations of lactate, glucose, and cortisol increased and the concentration of iron decreased in all cows (P ≤ .01)., Conclusions: Despite the limited number of cows evaluated, this report is the first to indicate lowered concentrations of calcitonin gene-related peptide as part of the metabolic changes during milk fever in cows. Further work with a larger cohort of animals is warranted to understand the precise role of calcitonin gene-related peptide and the potential associations with disturbances in plasma minerals typically observed during milk fever., (© 2013 American Society for Veterinary Clinical Pathology.)

Fifteen cows with milk fever were treated with 500ml of 40 % calcium borogluconate (group A) administered intravenously. Fifteen other cows with milk fever received the same treatment, supplemented with 500ml of 10 % sodium phosphate administered intravenously, and 80g calcium as calcium lactate and 70g inorganic phosphorus as sodium phosphate administered orally in drinking water. The cows were monitored and blood samples collected for 3 days to measure the concentrations of total and ionized calcium, inorganic phosphorus and magnesium and the activity of creatine kinase. The two groups did not differ significantly with respect to the course of the disease. In each group 14 cows were cured. A rapid and significant increase in serum calcium concentration from the hypo- to the hypercalcaemic range occurred in both groups within 10min of the start of treatment, followed by a slow and steady decrease to the hypocalcaemic range. Calcium lactate did not prevent the calcium concentration from returning to the hypocalcaemic range, and the calcium profiles of the two groups did not differ significantly. As expected, treatment had little effect on the concentration of inorganic phosphorus in group A. In group B, treatment caused a rapid increase in the concentration of inorganic phosphorus to a maximum 20min after the start of treatment. This was followed by a slow decrease in the phosphorus concentration to the normophosphataemic range. Our findings confirmed that combined intravenous and oral administration of sodium phosphate in cows with periparturient paresis attributable to hypocalcaemia and hypophosphataemia results in a rapid and sustained increase in serum phosphorus, but not in serum calcium concentration. This modified therapy did not improve the success rate of milk fever treatment and further studies are needed to improve treatment of periparturient paresis.

The oral administration of calcium lactate for prophylaxis of bovine parturient paresis has been promoted for a number of years. The goal of the present study was to investigate the effect of this treatment on the serum concentrations of calcium, inorganic phosphorus and magnesium in parturient cows. Five fresh calved cows were given a drench containing calcium lactate and 5 control cows received the same drench but without calcium lactate. There were no significant differences in the serum concentrations of total and ionised calcium and magnesium between treated and control cows within 24 hours of treatment. Because the calcium lactate drench did not significantly affect calcium concentrations in the blood of fresh cows, it appears highly questionable whether the administration of calcium lactate decreases the risk of bovine parturient paresis. Based on our results, the oral administration of calcium lactate can not be recommended for prophylaxis of bovine parturient paresis.

The objective was to describe the relationship between concentration of serum nonesterified fatty acids (NEFAs) at calving and the incidence of periparturient disorders in Chilean Holstein dairy cows (Bos taurus). The study was conducted at two dairies (central Chile) with 700 milking cows each and similar management. Between July 2006 and March 2007, 350 cows were selected, and concentrations of serum NEFAs were determined at calving. The incidence of milk fever (MF), retained fetal membranes (RFMs), metritis, and clinical mastitis from calving to 100 d in lactation were consistently recorded. The relationship between concentration of serum NEFAs at calving and the incidence of periparturient diseases was determined using logistic regression. The main explanatory variable was concentration of serum NEFAs at calving. The incidence of MF, RFM, metritis, and mastitis was 5.4%, 15.6%, 10.8%, and 14.4%, respectively. There was no association between concentration of NEFAs at calving and the incidence of these conditions when the median value of NEFAs (0.9 mEq/L) was used as a cutoff. However, when the 75th percentile (1.2 mEq/L) was used as the cutoff, cows with values <1.2 mEq/L were 0.45 and 0.32 times as likely to develop clinical mastitis and MF, respectively, compared with cows with values >or=1.2 mEq/L. When the 90th percentile (1.6 mEq/L) was used as a cutoff, cows with values <1.6 mEq/L were 0.25 times as likely to develop clinical mastitis compared with cows with values >or=1.6 mEq/L. As a continuous variable, for every 0.1 mEq/L increment in NEFAs at calving, cows were 1.11 times more likely to experience clinical mastitis. In conclusion, cows with NEFA concentrations >or=1.2 mEq/L had a higher incidence of clinical mastitis and MF than that of cows with values <1.2 mEq/L.

Objective: To identify serum biochemical and hematologic variables, as measured in the week before parturition, that predict postpartum retention of the placenta (RP) in dairy cows., Design: Retrospective cohort study., Animals: 1,038 cows in 20 commercial dairy herds., Procedures: Serum concentrations of fatty acids (FAs), beta-hydroxybutyrate, cholesterol, glucose, urea, and calcium and blood leukocyte, neutrophil, lymphocyte, monocyte, and eosinophil counts were determined. These variables were evaluated for an association with development of RP by use of a multivariate logistic regression model. Parity, season of parturition, existence of twins or dystocia, body condition score, and vitamin E treatment were included in the model as covariates., Results: High serum concentrations of cholesterol and FAs were associated with an increased odds of RP. There was a 5% relative increase in the odds of RP for each 0.1 mmol/L increase in cholesterol or FAs concentration in the week before parturition. Season of parturition and twinning were also identified as risk factors., Conclusions and Clinical Relevance: These associations indicated that prepartum energy metabolism contributes to the development of RP. Serum concentrations of cholesterol and FAs may be useful to identify cows with a metabolic abnormality or energy imbalance that might predispose them to RP and should be interpreted in conjunction with clinical risk factors such as twinning, dystocia, or parturient paresis.

Thirty cows with parturient paresis were divided into three groups of 10. All the cows were given 500 ml of a 40 per cent calcium borogluconate solution intravenously over a period of 10 minutes, and 20 were also given 500 ml of a 10 per cent solution of sodium phosphate intravenously; in 10 of the cows this solution was administered over a period of 10 minutes immediately after the calcium borogluconate solution, and in the other 10 cows 200 ml of the solution was administered rapidly and the remaining 300 ml was added to 10 litres of sodium chloride and glucose solution and infused slowly over six hours. There were no significant differences between the groups with respect to the outcome of the treatments; six or seven of the cows in each group stood within eight hours of the treatment. There were no significant differences between the changes in serum calcium concentrations among the groups. The mean concentrations of inorganic phosphorus in the groups given sodium phosphate were increased above the normal range initially, but after eight hours there were no significant differences between the groups in terms of the numbers of cows that were hypophosphataemic. There were no significant differences between the three groups with respect to changes after treatment in the serum concentrations of magnesium or parathyroid hormone.

The goal of this study was to investigate the efficacy of calcium chloride, sodium phosphate or a combination of these two substances administered orally immediately postpartum for the prevention of parturient paresis in cows. Thirty-two cows that had had parturient paresis at the previous calving, and in which serum biochemistry had shown hypocalcaemia and hypophosphataemia, were used in the study. The cows were transferred to the Department of Farm Animals, University of Zurich, five days before their expected due dates. On a randomized trial, the cows were given calcium chloride, sodium phosphate, both substances or no treatment (controls) via a stomach tube immediately postpartum and 12 hours later. The cows were monitored for 96 hours during which time blood was collected on a regular basis for the determination of total calcium, ionized calcium, inorganic phosphorus and magnesium concentrations. Of the 32 cows treated, 19 (59%) had parturient paresis and 13 (41%) did not. The incidence of parturient paresis did not differ significantly among the groups although there was a tendency for a lower incidence in cows treated with both calcium chloride and sodium phosphate. The various treatments had no apparent effect on serum calcium concentration. The concentration of inorganic phosphorus increased significantly in cows treated with sodium phosphate compared with the controls. The results of this study showed that cows treated with both calcium chloride and sodium phosphate orally tended to have a lower incidence of parturient paresis. Further investigation into multiple administrations of oral calcium chloride and sodium phosphate, started before parturition, for the prevention of parturient paresis is required.

The article describes the dynamics of changes in blood concentrations of the active substances present in the solution after its infusion to healthy cows in comparison to NaCI solution as well as the response of paretic cows to treatment with the new complex solution. Cows received a dose of 400 ml of A1 solution (containing 8.4 g of Ca2+) intravenously. In healthy cows the average calcium concentration in blood serum prior to the test was 2.52 +/- 0.08 mmol/l while 15 min. after the infusion the concentration rose to 3.10 +/- 0.08 mmol/l (p < 0.05) and magnesium concentration rose from 0.61 +/- 0.05 to 1.39 +/- 0.08 mmol/l (p < 0.05). This experiment showed that elevated concentration of non-organic phosphates persisted 1 hour after infusion (p < 0.05). In the second phase of efficacy evaluation of the novel preparation A1 on paretic cows the intravenous injection of 1 ml/kg of body weight of A1 solution increased calcium concentration up to almost normal level (p < 0.05). The level of magnesium in serum 1 h after injection was statistically significantly higher by 63% (p < 0.05) and reached the physiologically normal concentration. 1 h after the infusion of test solution the level of phosphate was higher by 13% (p > 0.05). The rise was statistically not significant. Even though A1 solution undoubtedly produced an increase in glucose concentration in the blood serum, due to wide dispersion of individual measurements and high standard deviation the increase (p > 0.05) in glucose concentration was found insignificant. Most of the treated paretic cows rose within 1-6 h after infusion of 400 ml of solution A1. No relapses were observed. A combination of different salts of calcium and magnesium, non-organic phosphates and glucose with analeptic substance mixed in one solution (A1 solution) administered at a dose of 1 ml/kg of body weight raises concentrations of essential macroelements in blood serum of cattle and promotes improvement of paretic cows condition.

In our previous study, it was demonstrated that the administration of anion salts, which slightly lower the dietary cation-anion difference (DCAD), in the prepartum period is safe and effective for preventing milk fever in multiparous cows. In the present study, several clinico-pathological constituents in serum and urine, which might be related to milk fever, were analyzed using stored samples from the previous study to identify clinico-pathological parameters for easily evaluating the efficacy of lowering DCAD and to further investigate the mechanism by which lowering DCAD prevents milk fever. Among the parameters analyzed in the present study, inorganic phosphorus (iP) was involved in milk fever because the serum concentration and urinary excretion of iP were significantly higher in the group of primiparous cows (heifer group), which did not develop hypocalcemia, than those in other groups of multiparous cows. Serum chloride concentrations in the heifer group and the group of multiparous cows fed anion salts (anion group) tended to remain higher than those in other control groups of multiparous cows suggesting that serum chloride concentration may be utilized for evaluating the status of metabolic acidosis and the efficacy of lowerng DCAD in dairy cows fed anion salts. In addition, plasma estradiol-17beta concentration in the heifer group tended to be lower at parturition compared with that in other multiparous groups suggesting that estrogen known as a potent inhibitor of bone resorption may be involved in developing milk fever.

The purpose of this prospective cohort study was to identify factors that place a dairy cow with uncomplicated milk fever (MF) at significant risk of becoming an alert downer cow (ADC) and to verify if these factors could be used to predict treatment outcome. Recumbent MF cows were examined before treatment and 52 were excluded due to complications. In all, histories and pretreatment serum samples were taken and the serum of 86 cows was analyzed for electrolyte levels (calcium, phosphorus, magnesium, and potassium). In total, 36 of the 86 samples were from ADCs and 50 from animals that responded to MF treatment (MFT). A binary-two-factor logistic model determined that a MF cow with a phosphorus pretreatment level of > or = 0.9 mmol/L was 12 times more likely not to become an ADC than one with a phosphorus level < 0.9 mmol/L (CI: 6.3,23.1). Also, a binary multivariable logistic regression analysis showed that a MF cow with a pretreatment calcium level > or = 1.7 mmol/L was 14 times more likely to become an ADC than one with a serum level < 1.7 mmol/L (CI: 2.0,98). Age and the other serum electrolytes were not statistically significant risk factors at the 0.05 level. The rigorous pretreatment examination and stringent adherence to protocol reduced ADC misclassification and fostered the strong association between single factor serum phosphorus levels and ADCs. By using a cutoff level of serum phosphorus at > or = 0.9 mmol/L, a practitioner could correctly predict that 95% of the MFs would not become ADCs and, therefore, this level would be a useful pretreatment predictor.

In the present study, we examined whether mildly altering dietary cation-anion difference (DCAD) contributes to the prevention of milk fever in dairy cows. Thirty multiparous cows and ten primiparous cows (heifer group) were used in this study and the multiparous cows were randomly divided into three groups of ten animals each (anion, non-anion and control groups). The cows in the anion group were given supplemental salts that slightly lowered DCAD. These salts consisted of 115 g of CaCO3, 42 g of CaHPO4, 65 g of MgSO4 x 7 H2O and 80 g of CaCl2 x 2 H2O as a daily dose for each cow, using a catheter from 21 days before the expected date of parturition until parturition. The cows in the non-anion group were given only the same Ca, Mg and ip supplement but no sulfate and chloride salts as that in the anion group. The cows in the control and heifer groups were not given any additional supplement. The incidence of hypocalcemia in the anion group decreased to approximately half of those in the non-anion and control groups, while the heifer group did not develop hypocalcemia at all. In addition, the number of days spent for the treatment of hypocalcemia and the number of drug bottles (calcium borogluconate solution) used for the treatment decreased to less than half in the anion group compared with those in the non-anion and control groups. At parturition, the serum Ca concentration in the control (6.2 +/- 1.9 mg/dl, mean +/- standard deviation) and non-anion groups (6.4 +/- 1.7 mg/dl) were significantly lower than that in the heifer group (8.3 +/- 0.4 mg/dl), and the level in the anion group was intermediate (7.3 +/- 1.3 mg/dl). The change in ionized Ca concentration was almost the same as that in serum Ca concentration, but only the concentration in the anion group tended to increase slightly from a week before parturition and was significantly higher than that in all other groups three days before parturition. Urinary pH in the anion group was maintained at a mildly acidic level (6.8-7.0) for the last two weeks before parturition, compared with those in the control (7.3-7.5) and non-anion groups (7.9-8.1), and similar to that in the heifer group (6.3-7.3). The urinary Ca excretion was the highest in the anion group among all groups during the prepartum period. There were no specific changes in the excretion of parathyroid hormone and 1,25-dihydroxyvitamin D in all groups of multiparous cows while the levels of these hormones remained low in the heifer group throughout the experimental period. The data in the present study indicates that the administration of anion salts that slightly lowered DCAD in the preparum period was effective for preventing milk fever in multiparous cows. Safe and mild metabolic acidosis induced by the anion salts could be evaluated by urinary pH (6.8-7.0), and might increase the responsiveness to Ca requirement at parturition through some complex mechanisms unrelated to the excretion of Ca-related hormones. In addition, it was clarified that primiparous cows have a high potential to respond to sudden Ca demand unrelated to hormone excretion, and their Ca metabolism was in some respects similar to that in multiparous cows fed anion salts. Therefore, manipulating mildly DCAD is expected to be an effective, safe and natural method for preventing milk fever in dairy cows.

The stress of parturition in the dairy cow is associated with increased susceptibility to infectious disease. During the periparturient period the demands for calcium are increased; these increased demands for calcium can result in subclinical or clinical hypocalcemia. Periparturient cows also experience significant immune suppression. Because intracellular calcium signaling is a key early feature in immune cell activation, we have hypothesized that the increased demand for calcium in periparturient cows may adversely affect intracellular calcium stores of immune cells. This reduction in intracellular calcium stores in immune cells could blunt intracellular calcium release following an activating stimulus, contributing to the immune suppression seen in these animals. To test this hypothesis, peripheral mononuclear cells were obtained from 27 multiparous dairy cows spanning a period of 2 wk before and 2 wk after parturition. Following activation of these cells by anti-CD3 antibodies plus secondary antibodies, intracellular calcium release from intracellular stores was measured. The intracellular calcium released in response to the activation signal declined as calcium demand for lactation became more intense and recovered as plasma calcium normalized. Intracellular calcium stores in peripheral mononuclear cells, estimated by pretreating cells with pervanadate and ionomycin, significantly decreased at parturition and returned to normal levels as the cows' blood calcium returned to normal levels. Hypocalcemia, which is common in periparturient dairy cows, is associated with decreased intracellular calcium stores in peripheral mononuclear cells. Our data suggest that this is the cause of a blunted intracellular calcium release response to an immune cell activation signal. It is concluded that intracellular Ca stores decrease in peripheral blood mononuclear cells (PBMC) before parturition and development of hypocalcemia. This suggests that systemic calcium stress precedes measurable hypocalcemia, particularly in cows that will develop milk fever. Therefore, PBMC intracellular Ca stores are a more sensitive measure of calcium stresses in transition cow. This decrease in PBMC intracellular Ca stores before parturition and the development of hypocalcemia contributes to periparturient immune suppression.

Metabolic diseases of cows represent the leading internal pathology in Lithuania in terms of incidence and economic impact. This paper summarizes the mineral metabolic state of milk cows, and details the influence of feeding on serum levels of calcium, nonorganic phosphorus, magnesium, potassium, sodium, glucose, total protein, and urea quantity, and correlationd among them, in healthy dry or post-calving cows as well as in cows with osteomalacia and milk fever after calving. There was less pronounced hypocalcaemia and there were only minor changes in phosphorus, magnesium, potassium and sodium in the serum of healthy dry and post-calving cows that had silage and mineral-vitamin supplements, compared to cows that did not have supplements and silage. There was a fall in calcium and phosphorus (to 1.89 +/- 0.12 mmol/L and 0.71 +/- 0.06 mmol/L, respectively) in the blood of cows sick with milk fever after calving, while levels of magnesium and potassium were increased. The correlation between calcium and phosphorus was r = 0.6993, p < 0.001 in the serum of sick cows. There was a fall in calcium, phosphorus and magnesium (to 1.86 +/- 0.46 mmol/L, 0.75 +/- 0.37 mmol/L, and 0.60 +/- 0.19 mmol/L, respectively) and an increase in sodium level (to 158.90 +/- 19.30 mmol/L) in the blood of cows with osteomalacia in comparison with healthy cows.

The objective of this study was to evaluate the correlation between serum calcium (Ca) and inorganic phosphorus (IP) values and urine pH of cows fed common rations without the addition of anionic salts in late pregnancy. One hundred and seven Holstein cows, having completed two or more lactations and with an expected calving date within the next seven days were selected from two herds. In order to determine levels of serum Ca and IP and urine pH, blood and urine samples were collected seven to one days before parturition. Of the 107 sampled cows, 17 developed recumbency after calving and were considered to be affected by milk fever. There were significant ( p<0.01 ) negative correlations between urine pH and serum Ca, IP and the ratio of Ca to IP, The urine pH, and levels of serum Ca and IP measured within 48 h prior to parturition differed significantly ( p<0.001 ) between recumbent and non-recumbent cows. The sensitivity, specificity, positive and negative predictive values of urine pH test 48 h prior to parturition, using a cut off level of above pH 8.25, were 100%, 81%, 55%, and 100%, respectively. These signify that monitoring urine pH within 48 h prior to parturition is a sensitive method to assess the risk of parturient paresis. The results of this study emphasize the importance of acid-base status of the animal in the pathophysiology of milk fever.

The aim of this study was to determine the effects of extracellular Ca(2+) concentration ([Ca(2+)](e)) on phagocytosis and intracellular Ca(2+) concentration ([Ca(2+)](i)) in bovine polymorphonuclear leukocytes (PMNs). The experiments were performed by using blood samples from parturient paretic and clinically normal parturient cows and manipulating the [Ca(2+)](e) in vitro. Phagocytosis by PMNs (with and without stimulation with phorbol myristate acetate and inhibition with cytochalasin B) and resting [Ca(2+)](i) were significantly lower in parturient paretic cows. Repletion of Ca(2+) in the extracellular media for the samples from these animals increased phagocytosis and resting [Ca(2+)](i). In the blood of clinically normal parturient cows, decreasing the [Ca(2+)](e) decreased phagocytosis and resting [Ca(2+)](i) in PMNs, but increasing the [Ca(2+)](e) did not affect phagocytosis. These results suggest that the hypocalcemic condition of parturient paretic cows in vivo causes decreased phagocytosis and resting [Ca(2+)](i) in PMNs, which may partly contribute to greater susceptibility to infection.

The composition and functional capacity of peripheral blood mononuclear leukocyte populations from dairy cows are altered substantially during the peripartal period. These changes are associated with a heightened susceptibility of the mammary gland to infection. It has been postulated that the metabolic demands associated with lactogenesis may impact negatively leukocyte function during the periparturient period. In the present study, serum immunoglobulin G1 concentration and functional capacities of peripheral blood mononuclear leukocytes from intact (n = 6) and mastectomized (n = 6) periparturient Jersey cows were evaluated and compared. Cell function assessments included lymphocyte proliferation, immunoglobulin M secretion, and interferon-gamma secretion by unstimulated and pokeweed mitogen stimulated mononuclear leukocytes. Data were summarized as mean responses for 5-d periods beginning 21 d prepartum and concluding at 19 d postpartum. The progressive decrease in serum immunoglobulin G in intact but not mastectomized cows before parturition likely was attributable to the selective uptake of this isotype by the mammary gland. Lymphocyte proliferation and secretion of interferon-gamma and polyclonal IgM by mitogen-stimulated leukocytes from intact cows decreased during the 15-d period before calving, reaching a nadir at 0 to 4 d postpartum. From 5 to 19 d postpartum, these functions often were comparable to those observed 2 to 3 wk prepartum. Functions of leukocytes from mastectomized cows did not change during the study period, although they often were of lower magnitude than those of cells from nonlactating cows. These results reconfirm the occurrence of a generalized reduction in blood mononuclear leukocyte function during the periparturient period. They also suggest that the reduction in leukocyte function during the period may be, in part, due to the physiologic demands imposed on the dairy cow by the lactating mammary gland.

To determine the effects of ozone on the phagocytosis of bovine polymorphonuclear leukocytes (PMNs), ozone gas was administered in vitro on the blood and milk of healthy lactating cows, cows with acute mastitis, and cows with milk fever. In the blood of healthy dairy cattle, although there was no significant effect of ozone gas on the viability of the leukocytes, phagocytosis of PMNs significantly decreased. In contrast, ozone gas administration in vitro significantly increased phagocytosis of PMNs from the blood of cows with acute mastitis and milk fever, and from mastitic milk. These findings showed that ozone administration in vitro has positive and negative effects on bovine PMN phagocytosis, depending on the health status of the animal.

Eight periparturient Holstein Friesian cows were examined for plasma tartrate-resistant acid phosphatase (TRAP) activity to assess the degree of bone metabolic activity and to evaluate the association between the change in calcium (Ca) concentration and bone metabolism during the periparturient period. Milk fever occurred in 1 of 8 cows just after parturition. Plasma TRAP activities did not markedly change in 5 of 8 cows during the experimental period. The changing rate of Ca between preparturition and just after parturition was under -20% in 3 of 8 cows, and low TRAP activities were observed in 2 of these 3 cows. This study suggests that cows with a low TRAP activity are at risk of developing milk fever in comparison to cows with high TRAP activity. Temporary increases of parathyroid hormone were observed in 7 cows, but not in the cow with milk fever.

Calcium (Ca) is essential for life in higher animals. It is involved in the normal functioning of a wide variety of tissues and physiologic processes which include bone formation, muscle contraction, nerve transmission, blood clotting and as a second messenger regulating the actions of many hormones. In order for these functions to be carried out properly, blood Ca concentrations must be monitored and regulated within strict limitations. The discovery of the vitamin D endocrine system has resulted in the realization that Ca regulation in mammals and birds involves a coordinated effort between the hormones parathyroid hormone (PTH), calcitonin and the hormonally-active form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Failure of this system to maintain normal blood Ca concentrations at parturition is a common occurrence in ruminants leading to clinical (periparturient paresis, milk fever) and subclinical hypocalcemia. Vitamin D sterols have played a significant role in efforts to avoid parturient hypocalcemia and this report will summarize advantages and disadvantages associated with their use.

The background to the development of a novel concept for the prepartal activation of calcium absorption capacity as a means of preventing parturient hypocalcaemia and milk fever in grazing ruminants is described. It was hypothesised that this objective could be achieved by decreasing the bio-availability of calcium from pasture for a 3 week period. Soya bean oil was chosen as a supplement, from a number of potential binding agents, to form poorly digestible calcium soaps in the gastrointestinal tract. 28 mature twin-pregnant ewes in late pregnancy were used as assay animals to test the hypothesis, and they proved to be a sensitive experimental model for dairy cows. Following the treatment period, overnight starvation was used to challenge calcium homeostasis. Calcium absorption capacity was assessed indirectly by measuring strontium concentrations in plasma following oral dosing with strontium chloride. Strong support for the hypothesis was obtained as the 14 Treated ewes were protected from severe fasting-induced hypocalcaemia (P = 0.002), and this was associated with a greatly increased capacity of the ewes to absorb calcium. The feeding strategy developed in this experiment led to the production of a Calcigard concentrate supplement which was subsequently shown to protect cows from hypocalcaemia and milk fever, and stimulate production.

Serum leptin concentrations were measured in antenatal and postnatal cows housed at two different locations. The mean serum leptin concentration was 9.2 +/- 0.6 ng/m l (n=22) in one group, and was slightly lower in the other (7.4 +/- 0.4 ng/ml, n=54), probably because of the different nutritional conditions between the two groups. There was no consistent variation in relation to the menstrual cycle and the periparturient period in both groups. Moreover, serum leptin concentrations during the periparturient period were independent of the number of delivery and the incidence of mastitis and milk fever. These results are quite different from those in rodents and human, suggesting the different regulatory mechanism of circulating leptin concentration in cows.

The correlation between the serum hydroxyproline concentration and serum activity levels of TRAP and BALP was examined in 41 cows. The correlated coefficient (r) was 0.6391 for TRAP and 0.3147 for BALP, respectively. Judging from the significant correlation to the serum hydroxyproline concentration, serum TRAP activity is an index for bone metabolism in cows. Serum TRAP activity was therefore measured in 205 healthy cows (2-9 years old) in order to observe the changes in bone resorption with aging and milk production. TRAP levels differed slightly between group A (< or =4 yrs) and B (5 yrs< or =) at the same stage of lactation. The activity levels rose slightly at the height of lactation stage and during the dry stage.

The objective of this study was to compare blood profiles of intact and mastectomized periparturient cows to discriminate those metabolic changes associated with the act of parturition from the metabolic changes caused by lactation. Mastectomized and intact cows had similar increases in plasma estrogens and cortisol concentrations around the time of calving. Mastectomy eliminated hypocalcemia and the rise in 9,13-di-cis retinoic acid observed in intact cows. Mastectomy reduced but did not eliminate decreases in plasma phosphorus, alpha-tocopherol, and beta-carotene associated with parturition in intact cows, suggesting the mammary gland is not the sole factor affecting plasma concentrations of these compounds. Dry matter intake was similar in both groups before calving. The day of calving, dry matter intake was lower in intact cows than in mastectomized cows, but after calving the mastectomized cows exhibited a pronounced decline in feed intake. Plasma nonesterified fatty acid (NEFA) concentrations rose rapidly in intact cows at calving and did not return to baseline level for > 10 d. In contrast, NEFA concentrations in mastectomized cow plasma rose moderately at calving and returned to baseline level 1 to 2 d after calving. This study provides evidence that hypocalcemia in the cow is solely a result of the calcium drain of lactation. The act of parturition affects blood phosphorus, dry matter intake, and NEFA concentration independent of the effect of lactation.

Calcium is tightly regulated in mammals because of the critical role of calcium ion concentrations in many physiological functions. In this work, we develop a model for calcium homeostasis and identify integral feedback control as a functional module that maintains this homeostasis. We argue that maintaining calcium concentrations in a narrow range and perfect adaptation seen when the calcium homeostatic mechanism is subjected to extreme disturbances are the result of a feedback control system implementing integral control through specific interactions of the regulating hormones. Based on the constraints imposed by the suggested integral control, we arrive at a simple dynamical model for calcium homeostasis. We show that the model is biologically plausible and is consistent with known physiology. Furthermore, the utility of the integral-feedback model is revealed by examining an extreme calcium perturbation, parturient paresis in dairy cows., (Copyright 2002 Academic Press.)

Milk fever occurring during the peripartum period has been suggested to be caused by fatty liver developed during the non-lactating stage because diseased cows have increased serum concentrations of non-esterified fatty acids (NEFA) and show hepatic lipidosis. In cows with fatty liver and related diseases such as ketosis, serum concentrations of apolipoprotein (apo) B-100 and apoA-I are decreased. The purpose of the present study was to examine whether apoB-100 and apoA-I concentrations are similarly decreased in cows with milk fever. Apolipoprotein concentrations were also measured in cows with downer syndrome, which has been suggested to be related, at least in part, to milk fever. Compared with healthy cows during early lactation, apoB-100 and apoA-I concentrations were decreased in cows with milk fever and also in downer cows. In cows with milk fever, the decreases in apoB-100 and apoA-I concentrations were associated with increased NEFA and decreased cholesterol and phospholipid concentrations. However, in downer cows, serum lipid concentration changes were not as distinct as in cows with milk fever. These results, coupled with previous findings on the decreases in apoB-100 and apoA-I concentrations of cows with fatty liver-related diseases, suggest that fatty liver is involved in the development of milk fever and partly in that of downer cow syndrome.

Certain blood parameters and clinical symptoms have been connected with milk fever and a hypocalcemic condition in the cow. The present study intended to establish a mutual connection between relevant blood parameters and potentially valuable background information about the cow and its observed clinical symptoms at calving. Two veterinarians were summoned within 12 h of parturition of 201 cows, distributed among 41 Danish commercial herds. Cows were at different parity levels (2 to 10) and breeds and management differed broadly among herds. A blood sample was taken from the vena jugularis or the tail vein and was subsequently analyzed in the laboratory. Furthermore, 13 different clinical symptoms were recorded as categorical data. We investigated associations among the data obtained. We assessed an interpretative model for actual blood calcium level with blood parameters and background knowledge of the animals. We established a path analysis using background knowledge, blood parameters, and results of clinical examinations to uncover causal connections among the variables. Twenty-six percent of the animals were diagnosed as having milk fever and subsequent blood analyses revealed a high frequency of hypocalcemia within the general range from 0.69 to 2.73 mmol of Ca per liter. Rectal temperature, inorganic blood phosphate, and potassium were all directly correlated with blood calcium, while glucose, lactate, and magnesium were inversely associated with calcium. Blood osteocalcin was significantly lower in hypocalcemic animals, indicating that de novo synthesis of bone was arrested during hypocalcemia. A mixed effect linear interpretative model explained 75% of the variation in blood calcium. Clinical symptoms like mood, appetite, muscle shivering, rumen motility, and paresis were individually correlated with blood calcium and were thereby predictive of hypocalcemia. The path analysis showed the central role of calcium in affecting the clinical symptoms. However, several other factors contributed to hypocalcemia.

Apolipoprotein (apo) C-III is a low-molecular-mass protein mainly distributed in the high-density lipoprotein fraction in cattle serum. We have recently shown that the apoC-III concentration is decreased in cows with fatty liver, ketosis, left displacement of the abomasum, retained placenta and milk fever. The decrease was most distinct in milk fever, thereby suggesting that apoC-III is particularly relevant to the development of milk fever and also that apoC-III is a candidate diagnostic marker for this disease. The purpose of the present study was to examine whether the apoC-III concentration in healthy cows is altered during the peripartum period, to assess the usefulness of apoC-III as a marker for milk fever. ApoC-III concentrations in 17 cows were monitored during the peripartum period (-48 to +12 days from parturition). Of the 17 cows, 14 were apparently healthy during the period. The apoC-III concentrations in the 14 healthy cows were unaltered during the period from -48 to -21 days, but thereafter showed individual variations. Compared with values during the period from -48 to -21 days, the apoC-III concentration was increased (137%) in 5 cows during the period from +1 to +12 days, whereas it decreased (60.7%) in 9 cows. Three cows suffered from milk fever at -3 to +10 days. Decreased apoC-III concentrations in diseased cows (15 to 37% of controls) were more distinct than in the 9 healthy cows. The apoC-III concentration was correlated with lecithin:cholesterol acyltransferase activity in cows with milk fever, but not in healthy cows. Correlation analysis also indicated that apoC-III and apoB-100 concentrations were negatively correlated in 5 healthy cows with increased apoC-III concentrations, but positively in 9 healthy cows with decreased concentrations and cows with milk fever. Determination of the apoC-III concentration during the peripartum period is suggested to be helpful in diagnosing milk fever. The possible relevance of apoC-III and apoB-100 in the development of milk fever is also implied.

To test the effects of a zeolite feed supplement on parturient calcium status and milk fever, two groups of dry cows were treated with either 1 kg of zeolite/d or none for 4 wk prepartum. At calving and d 1 and 2 after calving all cows were given 250 g of calcium carbonate as a drench, and a blood sample was taken. Serum calcium analysis revealed a greater calcium concentration in zeolite-treated cows. While three control cows contracted milk fever, necessitating intravenous calcium therapy, and six out of eight control cows experienced serum calcium levels below 2 mmol/L in one or more samples taken, none of the zeolite-treated cows contracted milk fever or experienced subclinical hypocalcemia.

Apolipoprotein (apo) C-III is a low molecular mass protein mainly distributed in the high-density lipoprotein (HDL) fraction. In cows with postparturient diseases such as ketosis, concentrations of cholesterol, phospholipids and apoA-I and the activity of lecithin:cholesterol acyltransferase, which are mainly distributed in or functionally associated with HDL, are reduced. The purpose of the present study was to examine whether the serum concentration of apoC-III was similarly decreased in the postparturient diseases. Compared with healthy controls, the apoC-III concentration was significantly (P<0.01) decreased in cows with fatty liver, ketosis, left displacement of the abomasum, milk fever and retained placenta. Concentrations of apoC-III in the HDL fractions from diseased cows were also lower than in controls. Of the diseased cows, the decreased apoC-III concentration was particularly distinct in cows with milk fever. Increased nonesterified fatty acid and reduced free cholesterol, cholesteryl ester and phospholipid concentrations were observed in cows with milk fever, as in the other diseased cows. The decrease in the apoC-III concentration is suggested to be closely associated with the postparturient disorders, in particular with milk fever.

Disodium ethylenediaminetetraacetate (Na2EDTA) has been used in infusion studies in cows and other species for more than 35 years, primarily for the induction of hypocalcemia as a model for milk fever. This paper reviews such studies and discusses blood calcium kinetics, toxicology, changes in various blood parameters and the effect on blood circulation, cardiac function and smooth muscle motility in the gastro-intestinal tract and in the pregnant uterus. It is concluded that Na2EDTA infusion may serve as a valid model for spontaneous hypocalcemia. However, experimental results may vary with factors such as the choice of method for blood total calcium analysis, and the rate of EDTA infusion. Standardization of these and certain other experimental conditions may greatly improve the comparability of results obtained in EDTA infusion studies. For cows, an infusion rate of 1.2 ml/kg/h of a 5% (w/v) solution, corresponding to 0.25 mmol/kg/min, has been suggested as a standard infusion.

Objective: To assess the effect of oral administration of CaCl2 gel on blood mineral concentrations, parturient disorders, reproductive performance, and milk production of dairy cows with retained fetal membranes (RFM)., Design: Randomized field trial., Animals: 20 cows that calved normally and were not treated with CaCl2 gel (group 1), 20 cows with RFM that were treated with CaCl2 gel (group 2), and 20 cows with RFM that were not treated with CaCl2 gel (group 3)., Procedure: Group-2 cows were treated orally with CaCl2 gel (54 g of calcium) 24 and 48 hours after parturition., Results: Administration of CaCl2 gel 24 and 48 hours after parturition did not have a significant effect on serum normalized calcium, total calcium, magnesium, or phosphorus concentrations or on incidence of metritis or left displacement of the abomasum, days to first insemination, pregnancy status after first insemination, or milk production., Conclusions and Clinical Relevance: Administration of CaCl2 gel 24 and 48 hours after parturition did not have significant effect on blood mineral concentrations, parturient disorders, reproductive performance, and milk production in dairy cows with RFM.

The efficacy of calcium propionate for the prevention of parturient paresis (milk fever) was compared with that of calcium chloride using 194 cows that had experienced milk fever during the previous calving. The cows were mainly of the Swedish Red and White and Swedish Friesian breeds and were divided randomly into an experimental group (n = 99) and a control group (n = 95). The cows in the experimental group received up to six boluses of 20 g of calcium as calcium propionate between 36 h before and 24 h after calving; the cows in the control group received up to four doses of 54 g of calcium as a commercially available oily solution of calcium chloride during the same period. Incidence of milk fever was recorded as the percentage of cows that were treated by a veterinarian because they showed clinical signs of the disease and had a blood calcium concentration less than 8.0 mg/dl. Twenty-five (25.3%) cows in the experimental group and 22 cows (23.2%) in the control group developed milk fever. The incidence of milk fever for cows in both groups was significantly lower than the 36.0% found in 713 cows that had experienced milk fever during their previous calving but received no prophylactic treatment. Therefore, calcium propionate was considered to have had a significant preventive effect, comparable with that of calcium chloride.

The collagen metabolites hydroxyproline (HYP), deoxypyridinoline (DPD) and pyridinoline (PYD) are suitable markers for bone resorption in humans and several animal species. In a field trial cows with symptoms of periparturient paresis (group A) and healthy control cows without symptoms (group B) were compared and urine and blood samples were collected on day 1, 2, 3, 4, 5, 9 and 14 after parturition. In group A the mean +/- SE serum Ca concentration on day 1 was 1.4 +/- 0.1 mmol/l whereas those of group B were 2.0 +/- 0.1 mmol/l. A significant increase of the corrected urinary HYP concentration was observed from parturition to day 14 (from 2.8 to 8.8 mumol/mmol creatinine) and the concentrations at the different times were higher in group A than in group B. The mean corrected total and free DPD and total PYD concentration in urine increased after parturition to reach a peak at day 9. For DPD and PYD the mean concentrations between the two groups did not differ significantly. The DPD and PYD are useful tools to follow bone resorption in dairy cows, although in our study no difference between the two groups could be found which means that both groups were able to mobilize Ca from bone.

This paper deals with blood levels of calcium (Ca), inorganic phosphorus, parathyroid hormone and 1,25-dihydroxyvitamin D in 6 cows treated for milk fever. Four of the cows stood within 1 day after Ca therapy, whereas 2 other cases showed an unsatisfactory response to Ca therapy and did not rise. The necropsy revealed microscopic necrotic myocardial lesions scattered in the heart of these 2 unrecovered cows. The degree of hypocalcemia and hypophosphatemia were similar in the 6 cows. However, the recovery from hypophosphatemia was markedly delayed in the cows will an unsatisfactory response.

Objective: To determine effect of prophylactic treatment of dairy cattle with a calcium chloride gel on serum calcium concentration in the immediate postpartum period and incidence of parturient paresis, retained fetal membranes, and displacement of the abomasum., Design: Randomized controlled trial., Animals: 204 Holstein cows., Procedure: Cows were paired according to parity, whether they had previously had parturient paresis, and expected calving date. Cows in the treatment group received doses of calcium chloride gel 12 hours before expected calving, at calving, and 12 and 24 hours after calving. Cows in the control group did not receive calcium chloride gel., Results: Compared with concentration in the control cows, mean serum calcium concentration in cows treated with calcium chloride gel was significantly increased on postcalving days 1 and 2. The increase was significant only in cows that were third parity or greater. Calcium chloride gel treatment also resulted in significantly reduced incidence of parturient paresis, parturient hypocalcemia, and displaced abomasum. The incidence of parturient paresis was lower in cows that received the precalving dose of calcium chloride gel (0/39) than in cows that did not receive the precalving dose (5/63)., Clinical Implications: Results suggest that periparturient prophylactic treatment of dairy cattle with an oral calcium chloride gel may be beneficial and that treatment would be most effective for cows of third parity or greater. Administration of a precalving dose of calcium chloride gel is necessary to reduce the incidence of parturient paresis, but postcalving treatment alone has other beneficial effects.