Acute hypernatremia and hypocalcemia after oral sodium phosphate administration to a dog.

A 15-year-old male neutered mixed breed dog weighing 28 kg presented to a referral center after developing severe tremors and altered mentation. There was hypocalcemia and hypernatremia after oral administration of sodium phosphate as a bowel cleansing agent in preparation for colonoscopy. The dog was treated intravenously with low sodium fluids and calcium gluconate. Neurologic status and electrolyte derangements normalized over the next 12 hours. Oral administration of sodium phosphate appeared to cause clinical electrolyte derangements in this dog.

Predictors of blood ionized calcium concentration in sick adult cattle.

BACKGROUND: Data on the factors affecting blood ionized calcium concentration (ciCa2+ ) and diagnostic performance of serum total calcium concentration (ctCa) measurements to detect abnormal blood iCa2+ status are lacking in sick adult cattle. OBJECTIVE: Assess the association of ciCa2+ with venous blood pH, plasma concentrations of chloride (cCl), sodium (cNa), and potassium (cK), and ctCa, and total protein, albumin, and globulin concentrations in sick adult cattle. ANIMALS: Two-hundred and sixty-five adult cattle (≥1-year-old) with different diseases. METHODS: Prospective study. Whole blood pH, ciCa2+ , cNa, cK, and cCl were measured using a blood gas and electrolyte analyzer, whereas ctCa, and total protein, and albumin concentrations were determined using an autoanalyzer. The relationship between ciCa2+ and venous blood pH, plasma cCl, cNa, cK, and ctCa, and total protein, albumin, and globulin concentrations was investigated. Sensitivity and specificity were calculated for ctCa for diagnosis of abnormal ciCa2+ . RESULTS: Sensitivity of ctCa measurements to detect abnormal ciCa2+ was 66.0% whereas specificity of ctCa measurements was 72.3%. Serum total calcium concentration measurements accounted for 42% of adjusted blood ionized calcium (iCa2+ 7.40 ) concentration variance. Plasma cCl, and cK had explanatory power of ciCa2+ 7.40 , accounting for an additional 21% and 9% of the variance, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum tCa measurements failed to accurately predict blood iCa2+ status in ill adult cattle. Serum tCa concentrations and plasma cCl were the strongest predictors of ciCa2+ in sick adult cattle.

Identification of genetic variants and individual genes associated with postpartum hypocalcemia in Holstein cows.

Periparturient hypocalcemia is a complex metabolic disorder that occurs at the onset of lactation because of a sudden irreversible loss of Ca incorporated into colostrum and milk. Some cows are unable to quickly adapt to this demand and succumb to clinical hypocalcemia, commonly known as milk fever, whereas a larger proportion of cows develop subclinical hypocalcemia. The main goal of this study was to identify causative mutations and candidate genes affecting postpartum blood calcium concentration in Holstein cows. Data consisted of blood calcium concentration measured in 2513 Holstein cows on the first three days after parturition. All cows had genotypic information for 79 k SNP markers. Two consecutive rounds of imputation were performed: first, the 2513 Holstein cows were imputed from 79 k to 312 k SNP markers. This imputation was performed using a reference set of 17,131 proven Holstein bulls with 312 k SNP markers. Then, the 2513 Holstein cows were imputed from 312 k markers to whole-genome sequence data. This second round of imputation used 179 Holstein animals from the 1000 Bulls Genome Project as a reference set. Three alternative phenotypes were evaluated: (1) total calcium concentration in the first 24 h postpartum, (2) total calcium concentration in the first 72 h postpartum calculated as the area under the curve; and (3) the recovery of total calcium concentration calculated as the difference in total calcium concentration between 72 and 24 h. The identification of genetic variants associated with these traits was performed using a two-step mixed model-based approach implemented in the R package MixABEL. The most significant variants were located within or near genes involved in calcium homeostasis and vitamin D transport (GC), calcium and potassium channels (JPH3 and KCNK13), energy and lipid metabolism (CA5A, PRORP, and SREBP1), and immune response (IL12RB2 and CXCL8), among other functions. This work provides the foundation for the development of novel breeding and management tools for reducing the incidence of periparturient hypocalcemia in dairy cattle.

Circulating parathyroid hormone and serotonin in multiparous cows with differing postparturient serum calcium concentrations.

Many multiparous dairy cows experience subclinical hypocalcemia (SCH) in the immediate postpartum period as they adapt to the demands of lactation. Furthermore, differing dynamics of SCH in the days following parturition are associated with varied health and production outcomes, with cows experiencing transient SCH producing more milk and facing fewer negative health events than cows with delayed or persistent SCH. Our objectives were to describe differences in mediators of calcium (Ca) homeostasis between cows experiencing differing Ca dynamics postpartum. A prospective cohort of 89 multiparous Holstein cows from 2 herds in New York were classified into 1 of 4 SCH groups based on mean serum total Ca (tCa) at 1 and 4 d in milk (DIM): normocalcemic (NC; [tCa] >1.89 mmol/L at 1 DIM and >2.25 mmol/L at 4 DIM, n = 30); transient SCH (tSCH; [tCa] ≤1.89 mmol/L at 1 DIM and >2.25 mmol/L at 4 DIM, n = 12); delayed SCH (dSCH; [tCa] >1.89 mmol/L at 1 DIM and ≤2.25 mmol/L at 4 DIM, n = 23); and persistent SCH (pSCH; [tCa] ≤1.89 mmol at 1 DIM and ≤2.25 mmol/L at 4 DIM, n = 24). Blood samples were collected at -5, -1, 1 through 5, 7, and 10 DIM and analyzed for tCa, parathyroid hormone (PTH), and serotonin. Repeated measures ANOVA models were used to analyze differences between SCH groups and changes over time for tCa, PTH, and serotonin. During the prepartum period, tCa was greater in the NC, tSCH, and dSCH cows as compared with the pSCH cows and there was marginal evidence for a difference in PTH between SCH groups. Postpartum tCa varied over time between SCH groups. Mean postpartum (95% confidence interval) tCa for respective SCH groups were NC = 2.32 (2.28, 2.35) mmol/L; tSCH = 2.20 (2.14, 2.25) mmol/L; dSCH = 2.17 (2.13, 2.21) mmol/L; and pSCH = 2.03 (1.99, 2.07) mmol/L. Mean concentrations of PTH in the postpartum period were NC = 70.1 (66.2, 74.4) pmol/L; tSCH = 72.1 (66.1, 79.2); dSCH = 75.8 (70.8, 81.5) pmol/L; and pSCH = 77.7 (72.4, 83.9) pmol/L. Serotonin was similar between SCH groups pre- and postpartum and followed a cyclical pattern from 1 to 10 DIM. Our results agreed with our hypothesis that differences in postpartum PTH might exist between cows experiencing different dynamics of SCH in the early lactation period; however, further studies are needed to confirm this difference. If true, this would suggest that Ca homeostasis may be disrupted in cows with dSCH and pSCH. Gaining a better understanding of these modulatory differences may aid in the prevention, management, and treatment of SCH.

Evaluation of the relationship between ionized and total calcium concentrations in blood during the first week of lactation in dairy cows.

BACKGROUND: Diagnosis of subclinical hypocalcemia in cattle is based on concentration of total Ca ([TCa]) in serum or plasma below the reference range, with [TCa] serving as proxy for the concentration of ionized Ca ([iCa]). HYPOTHESIS/OBJECTIVES: To investigate the relation between [iCa] and [TCa] in periparturient cows over time, and its association with various metabolites. ANIMALS: Thirty periparturient dairy cows. METHODS: Prospective observational study. Blood from periparturient cows was obtained between 4 days before and 7 days after calving. Samples underwent blood gas analysis and blood biochemical analysis. The ratio of [iCa] : [TCa] was computed. Repeated measures linear regression analyses, spearman correlation-, Deming regression- and receiver operating characteristic (ROC) analyses were conducted. RESULTS: Correlations between [iCa] and [TCa] ranged from r = 0.55 to r = 0.84. The diagnostic value of [TCa] to identify cows with [iCa] below the arbitrary cut-off of 1.1 mmol/L was weak in particular during the first 24 hours of lactation, but continuously improved toward the end of the study with areas under the ROC curve increasing from 0.64 at d 0 to 0.93 at d +4 after calving. Strongest association with [iCa] : [TCa] were found for albumin (r2 = 0.58, P < .0001), pCO2 (r2 = 0.45, P = .0003), the standard [HCO3 ] (r2 = 0.22, P = .01), lactate (r2 = 0.16, P = .04) and [NEFA] (r2 = 0.15, P = .05). CONCLUSION AND CLINICAL IMPORTANCE: The [TCa] is of limited value to identify cows with subnormal [iCa] in the first hours and days of lactation, a finding apparently attributable to the increased variation of a number of metabolic variables that affect the ratio of [iCa] : [TCa].

Perspective: Transient postparturient hypocalcemia-A lactation-induced phenomenon of high-producing dairy cows.

Milk fever is one of the most historically relevant diseases of dairy cows. It is caused by tremendous calcium (Ca) expenditure at the initiation of lactation, so severe that cows can no longer stand and, if left untreated, die. Fortunately, through prepartum nutritional improvements, this version of clinical hypocalcemia is rare in the United States. Nonetheless, the opinion that all versions of postpartum hypocalcemia are detrimental remains pervasive, which is particularly significant given that 50% of cows are subclinically hypocalcemic after calving. This has led to a variety of available management and treatment strategies, ranging from prepartum dietary programs to postpartum Ca gels and boluses, targeted at preventing hypocalcemia in dairy cows. Recent research has determined that postpartum dairy cows can experience different types of subclinical hypocalcemia: transient, persistent, or delayed. We now know cows experiencing transient hypocalcemia as part of the homeorhetic adaptation to lactation are the highest milk producers in modern dairy herds, whereas cows with hypocalcemia several days after calving experience disease and losses in milk production. Therefore, it is wrong to assume all postpartum hypocalcemia is detrimental and that treatment of all cases is considered necessary and beneficial. Research indicates that milk synthesis at the onset of lactation contributes to immediate postpartum hypocalcemia, and that the mammary gland is a critical factor in management of Ca homeostasis. However, cows differ in their ability to manage this phenomenon, and it is possible that immediate postpartum influences such as dry matter intake, inflammation, and immune activation affect appropriate Ca regulation in the days following calving.

Feline precision medicine using whole-exome sequencing identifies a novel frameshift mutation for vitamin D-dependent rickets type 2.

OBJECTIVES: A 14-week-old female domestic longhair kitten presented with shifting lameness and disproportionately smaller size compared with a co-housed littermate. METHODS: Hematology and serum biochemical testing were conducted to investigate causes for delayed growth, and radiographs of the appendicular skeleton were obtained. RESULTS: The afflicted kitten had marked hypocalcemia, mild hypophosphatemia and substantial elevations in alkaline phosphatase activity, as well as pathognomonic radiographic findings consistent with rickets. Skeletal changes and hypocalcemia prompted testing of concentrations of parathyroid hormone (PTH) and vitamin D metabolites. Endocrine testing demonstrated significant increases in serum concentrations of PTH and 1,25-dihydroxycholecalciferol (calcitriol), supporting a diagnosis of vitamin D-dependent rickets type 2. Provision of analgesia, supraphysiologic doses of calcitriol and calcium carbonate supplementation achieved normalization of the serum calcium concentration and restoration of normal growth, although some skeletal abnormalities persisted. Once skeletally mature, ongoing calcitriol supplementation was not required. Whole-exome sequencing (WES) was conducted to identify the underlying DNA variant. A cytosine deletion at cat chromosome position B4:76777621 in VDR (ENSFCAT00000029466:c.106delC) was identified and predicted to cause a stop codon in exon 2 (p.Arg36Glufs*18), disrupting >90% of the receptor. The variant was unique and homozygous in this patient and absent in the sibling and approximately 400 other cats for which whole-genome and whole-exome data were available. CONCLUSIONS AND RELEVANCE: A unique, heritable form of rickets was diagnosed in a domestic longhair cat. WES identified a novel frameshift mutation affecting the gene coding for the vitamin D3 receptor, determining the likely causal genetic variant. Precision medicine techniques, including whole-exome and whole-genome sequencing, can be a standard of care in cats to identify disease etiologies, and to target therapeutics and personalize treatment.

Store-operated Ca2+ entry-sensitive glycolysis regulates neutrophil adhesion and phagocytosis in dairy cows with subclinical hypocalcemia.

Hypocalcemia in dairy cows is associated with a decrease of neutrophil adhesion and phagocytosis, an effect driven partly by changes in the expression of store-operated Ca2+ entry (SOCE)-related molecules. It is well established in nonruminants that neutrophils obtain the energy required for immune function through glycolysis. Whether glycolysis plays a role in the acquisition of energy by neutrophils during hypocalcemia in dairy cows is unknown. To address this relationship, we performed a cohort study and then a clinical trial. Neutrophils were isolated at 2 d postcalving from lactating Holstein dairy cows (average 2.83 ± 0.42 lactations, n = 6) diagnosed as clinically healthy (CON) or with plasma concentrations of Ca2+ <2.0 mmol/L as a criterion for diagnosing subclinical hypocalcemia (HYP, average 2.83 ± 0.42 lactations, n = 6). In the first experiment, neutrophils were isolated from blood of CON and HYP cows and used to analyze aspects of adhesion and phagocytosis function through quantitative reverse-transcription PCR along with confocal laser scanning microscopy, mRNA expression of the glycolysis-related gene hexokinase 2 (HKII), and components of the SOCE moiety ORAI calcium release-activated calcium modulator 1 (ORAI1, ORAI2, ORAI3, stromal interaction molecule 1 [STIM1], and STIM2). Results showed that adhesion and phagocytosis function were reduced in HYP cows. The mRNA expression of adhesion-related syndecan-4 (SDC4), integrin ß9 (ITGA9), and integrin ß3 (ITGB3) and phagocytosis-related molecules complement component 1 R subcomponent (C1R), CD36, tubulinß1 (TUBB1) were significantly decreased in the HYP group. In the second experiment, to address how glycolysis affects neutrophil adhesion and phagocytosis, neutrophils isolated from CON and HYP cows were treated with 2 µM HKII inhibitor benserazide-d3 or 1 µM fructose-bisphosphatase 1 (FBP1) inhibitor MB05032 for 1 h. Results revealed that the HKII inhibitor benserazide-d3 reduced phagocytosis and the mRNA abundance of ITGA9, and CD36 in the HYP group. The FBP1 inhibitor MB05032 increased adhesion and phagocytosis and increased mRNA abundance of HKII, ITGA9, and CD36 in the HYP group. Finally, to investigate the mechanism whereby SOCE-sensitive glycolysis affects neutrophil adhesion and phagocytosis, isolated neutrophils were treated with 1 µM SOCE activator thapsigargin or 50 µM inhibitor 2-APB for 1 h. Results showed that thapsigargin increased mRNA abundance of HKII, ITGA9, and CD36, and increased adhesion and phagocytosis in the HYP group. In contrast, 2-APB decreased mRNA abundance of HKII and both adhesion and phagocytosis of neutrophils in the CON group. Overall, the data indicated that SOCE-sensitive intracellular Ca2+ levels affect glycolysis and help regulate adhesion and phagocytosis of neutrophils during hypocalcemia in dairy cows.

Associations between days in the close-up group and milk production, transition cow diseases, reproductive performance, culling, and behavior around calving of Holstein dairy cows.

The objective of experiment I was to evaluate the association between days in the close-up group (DINCU) and milk production, early lactation diseases, reproductive performance, and culling. In experiment II behavioral changes associated with DINCU were evaluated using a neck-mounted sensor (Smarttag neck, Nedap Livestock Management, Groenlo, the Netherlands). Cow-lactations of 28,813 animals from 14,155 individual cows of 2 farms in northern Germany and western Slovakia, calving between January 2015 and December 2020, were included in the study. After exclusion of cows with a gestation length <262 and >292 d and cows with >42 DINCU data from 8,794 and 19,598 nulliparous and parous cows, respectively, were available for final statistical analyses. To analyze the association between DINCU and second test-d 305-d mature-equivalent milk projection, linear mixed models were calculated. Binary data (i.e., clinical hypocalcemia, hyperketonemia, retained placenta [RP], acute puerperal metritis [APM], mastitis, left displaced abomasum [LDA], first service pregnancy risk) were analyzed using logistic regression models. To analyze the association between DINCU and culling or death during the first 300 DIM Cox proportional hazards were used. To analyze the association between DINCU and behavior 7 d before to 7 d after calving (i.e., activity, inactivity, eating, ruminating time), linear mixed models were calculated. Nulliparous cows with a short (<10 DINCU) and a long stay (>30 DINCU) in the close-up group had a lower milk production an increased risk for hyperketonemia, RP, and APM compared with nulliparous cows with DINCU between 21 to 28 d. Parous cows with a short (<10 DINCU) and a long stay (>30 DINCU) in the close-up group had a lower milk production, an increased risk for RP and mastitis, a reduced first service pregnancy risk, and an increased culling risk, compared with parous cows with DINCU between 21 to 28 d. Furthermore, the risk for clinical hypocalcemia and LDA was increased in parous cows with >30 DINCU compared with parous cows with <30 DINCU. The risk for APM was increased in parous cows with <10 DINCU compared with parous cows with >10 DINCU. In nulliparous cows no association was found between DINCU and the risk for left displaced abomasum and mastitis. In experiment II, cows with 7 and 35 DINCU had an impaired behavior around calving compared with cows with 14, 21, and 28 DINCU. During the last 7 d before parturition, these cows were more inactive and had a reduced eating and ruminating time. After calving, cows with 7 DINCU spent less time eating. In conclusion, cows with <10 DINCU and cows with >30 DINCU had a lower milk production, a higher risk to incur diseases and an impaired behavior, especially before calving.

A randomized field trial assessing the timing of postpartum calcium bolus administration on milk yield of multiparous Holstein cows.

Recent studies have shown that cows with subclinical hypocalcemia (SCH) at 4 d in milk (DIM), regardless of their blood Ca concentration before that time point, suffer from an increased early-lactation disease risk and reduced milk yield, whereas cows experiencing a transient reduction in blood Ca that regain normocalcemia by 4 DIM are at a reduced risk of disease and have greater milk yields. With a goal of improving outcomes for dyscalcemic cows with SCH at 4 DIM, our primary objective was to assess the effect of a herd-level oral Ca bolus strategy that delayed supplementation to 24 and 48 h postpartum on productive performance of multiparous Holstein cows. Our secondary objectives were to assess the effects of delayed Ca bolus supplementation on blood Ca concentration, disease incidence within 30 DIM, and pregnancy risk to first service. At calving, multiparous cows on a single commercial dairy farm in Iran were randomly assigned to 1 of 3 treatment groups: (1) control, no Ca bolus administration (CON; n = 95); (2) traditional bolus, one Ca bolus administered immediately following calving and a second Ca bolus administered 24 h after calving (TRD, n = 102); or (3) experimental bolus, one Ca bolus administered 24 h after calving with a second Ca bolus administered 48 h after calving (EXP, n = 99). Blood samples were collected at 0, 24, 48, 72, and 96 h, and 7 d after parturition, with sampling occurring before bolus administration for the TRD (0 and 24 h) and EXP (24 and 48 h) groups. A general linear mixed model was created to analyze the change milk yield over the first 4 monthly tests and serum Ca concentrations over 7 DIM. Given the lack of disease events diagnosed within 30 DIM, no statistical analysis was conducted for this outcome. The effect of treatment group on risk of pregnancy to first service was assessed using Poisson regression. The incidence of dyscalcemia within CON cows was 72%. We found no difference in mean monthly milk yield among treatment groups across the first 4 tests, with an average monthly production of 51.8 ± 8.8 kg/d for CON cows, 52.5 ± 8.7 kg/d for TRD cows, and 51.8 ± 8.7 kg/d for EXP cows. Mean blood Ca concentration also did not differ across 7 DIM among treatment groups and was 2.04 mmol/L [95% confidence interval (CI) = 2.00 to 2.07 mmol/L] for CON cows, 2.06 mmol/L (95% CI = 2.03 to 2.09 mmol/L) for TRD cows, and 2.09 mmol/L (95% CI = 2.05 to 2.12 mmol/L) for EXP cows. The risk of pregnancy to first service was numerically greater for CON than TRD and EXP cows but not statistically different; however, our study was underpowered for this outcome. Under the conditions of our study, our findings suggest that delaying oral Ca bolus supplementation to 24 and 48 h postpartum has no effect on milk production across the first 4 monthly tests.

Calcium dynamics and associated temporal patterns of milk constituents in early-lactation multiparous Holsteins.

At the onset of lactation, calcium (Ca) homeostasis is challenged. For the transitioning dairy cow, inadequate responses to this challenge may result in subclinical hypocalcemia at some point in the postpartum period. It has been proposed that dynamics of blood Ca and the timing of subclinical hypocalcemia allow cows to be classified into 4 Ca dynamic groups by assessing serum total Ca concentrations (tCa) at 1 and 4 days in milk (DIM). These differing dynamics are associated with different risks of adverse health events and suboptimal production. Our prospective cohort study aimed to characterize the temporal patterns of milk constituents in cows with differing Ca dynamics to investigate the potential of Fourier-transform infrared spectroscopic (FTIR) analysis of milk as a diagnostic tool for identifying cows with unfavorable Ca dynamics. We sampled the blood of 343 multiparous Holsteins on a single dairy in Cayuga County, New York, at 1 and 4 DIM and classified these cows into Ca dynamic groups using threshold concentrations of tCa (1 DIM: tCa <1.98 mmol/L; 4 DIM: tCa <2.22 mmol/L) derived from receiver operating characteristic curve analysis based on epidemiologically relevant health and production outcomes. We also collected proportional milk samples from each of these cows from 3 to 10 DIM for FTIR analysis of milk constituents. Through this analysis we estimated the milk constituent levels of anhydrous lactose (g/100 g of milk and g/milking), true protein (g/100 g of milk and g/milking), fat (g/100 g of milk and g/milking), milk urea nitrogen (mg/100 g of milk), fatty acid (FA) groups including de novo, mixed origin, and preformed FA measured in grams/100 g of milk, by relative percentage, and grams/milking, as well as energy-related metabolites including ketone bodies and milk-predicted blood nonesterified FA. Individual milk constituents were compared among groups at each time point and over the entire sample period using linear regression models. Overall, we found differences among the constituent profiles of Ca dynamic groups at approximately every time point and over the entire sample period. The 2 at-risk groups of cows did not differ from each other at more than one time point for any constituent, however prominent differences existed between the milk of normocalcemic cows and the milk of the other Ca dynamic groups with respect to FA. Over the entire sample period, lactose and protein yield (g/milking) were lower in the milk of at-risk cows than in the milk of the other Ca dynamic groups. In addition, milk yield per milking followed patterns consistent with previous Ca dynamic group research. Though our use of a single farm does limit the general applicability of these findings, our conclusions provide evidence that FTIR may be a useful method for discriminating between cows with different Ca dynamics at time points that may be relevant in the optimization of management or development of clinical intervention strategies.

Considerations in the Diagnosis and Treatment of Early Lactation Calcium Disturbances.

This article reviews the history of clinical hypocalcemia and the evolving definition of subclinical hypocalcemia, targeting a concept for consideration that not all hypocalcemia is negative. With a goal of presenting bovine practitioners information to assist with individual animal hypocalcemia diagnosis and treatment as well as herd-level monitoring and prevention, we present current methods of direct calcium measurement, therapeutic interventions for clinical hypocalcemia, and postpartum calcium supplementation options and their efficacy. We encourage veterinarians to understand calcium dynamics in the immediate postpartum period and evaluate how individual cow therapy and herd prevention protocols can assist with supporting calcium regulation.

Evaluating the inclusion of alfalfa hay in diets fed to multigravid Holstein cows in their transition to early lactation.

The objectives of this study were to determine the dry matter intake (DMI), urine pH, Ca concentration in blood, Ca output in urine, and frequency of hypocalcemia in pregnant and nonlactating dairy cows consuming diets containing different hays and acidogenic products during the prepartum period. Eighty pregnant and nonlactating Holstein cows approaching their second or greater calving were fed 1 of 4 experimental diets according to a 2 × 2 factorial arrangement of treatments during the prepartum period (21 d before calving). Diets included either grass hay (GH) or alfalfa hay (AH) and calcium chloride (CL) or polyhalite (PO) as the acidogenic products. All diets had a dietary cation-anion difference (DCAD) below -190 mEq/kg of dry matter (DM). Grass hay contained 75 g/kg crude protein, 749 g/kg neutral detergent fiber, 3.6 g/kg Ca, 0.9 g/kg Na, 18.8 g/kg K, 3.8 g/kg Cl, 1.5 g/kg S, and a cation-anion difference equal to 290 mEq/kg of DM. Alfalfa hay contained 196 g/kg crude protein, 456 g/kg neutral detergent fiber, 15.2 g/kg Ca, 1.6 g/kg Na, 25 g/kg K, 7.7 g/kg Cl, 3.2 g/kg S, and a cation-anion difference equal to 292 mEq/kg of DM. Cows consuming GH tended to consume more DM than cows consuming AH (11.6 vs. 10.8 kg/d) but DMI did not differ between acidogenic products. Urine pH decreased below 6.5 for all diets, although cows consuming the GHPO diet had the highest urine pH. The concentration of Ca in plasma decreased substantially around calving but neither hay type nor acidogenic product affected it. Urinary Ca output was lowest for cows consuming the GHPO diet. No associations existed between dietary treatments and the frequencies of normocalcemia and hypocalcemia. Under the conditions of this study, in which alfalfa and grass hays had similar cation-anion differences, we concluded that the inclusion of alfalfa hay in prepartum diets does not necessarily increase the frequency of hypocalcemia. The cation-anion difference of the alfalfa hay, more than the concentration of potassium alone, may be a key determinant of whether alfalfa hay fits in a prepartum feeding program for prepartum dairy cows. Further research should explore this relationship.

Blood calcium concentration and performance in periparturient and early lactating dairy cows is influenced by plant bioactive lipid compounds.

Previous studies ex vivo suggested that plant bioactive lipid compounds (PBLC) can increase ruminal calcium absorption. Therefore, we hypothesized that PBLC feeding around calving may potentially counteract hypocalcemia and support performance in postpartum dairy cows. The corresponding aim of the study was to investigate the effect of PBLC feeding on blood minerals in Brown Swiss (BS) and hypocalcemia-susceptible Holstein Friesian (HF) cows during the period from d -2 to 28 relative to calving and on milk performance until d 80 of lactation. A total of 29 BS cows and 41 HF cows were divided each into a control (CON) and PBLC treatment group. The latter was supplemented with 1.7 g/d menthol-rich PBLC from 8 d before expected calving to 80 d postpartum. Milk yield and composition, body condition score and blood minerals were measured. Feeding PBLC induced a significant breed × treatment interaction for iCa, supporting that PBLC increased iCa exclusively in HF cows; the increase was 0.03 mM over the whole period and 0.05 mM from d 1 to 3 after calving. Subclinical hypocalcemia was seen in one BS-CON and 8 HF-CON cows and 2 BS-PBLC and 4 HF-PBLC cows. Clinical milk fever was detected only in HF cows (2 HF-CON and one HF-PBLC). Other tested blood minerals, such as sodium, chloride, and potassium, as well as blood glucose, were neither affected by PBLC feeding nor breed, nor were their 2-way interactions, except for higher sodium levels in PBLC cows on d 21. Body condition score showed no effect of treatment, except for a lower body condition score in BS-PBLC compared with BS-CON at d 14. Dietary PBLC increased milk yield, milk fat yield, and milk protein yield at 2 consecutive dairy herd improvement test days. As indicated by treatment × day interactions, energy-corrected milk yield and milk lactose yield were increased by PBLC on the first test day only, and milk protein concentration decreased from test d 1 to test d 2 in CON only. The concentrations of fat, lactose, and urea, as well as somatic cell count, were not affected by treatment. The weekly milk yield over the first 11 wk of lactation was 29.5 kg/wk higher for PBLC versus CON across breeds. It is concluded that the applied PBLC induced a small but measurable improvement of calcium status in HF cows in the study period and had additional positive effects on milk performance in both breeds.

Eucalcemia during lipopolysaccharide challenge in postpartum dairy cows: II. Calcium dynamics.

Hypocalcemia induced by immune activation is a conserved response among mammals. Early postpartum cows will experience decreased circulating Ca concentrations following acute immune activation; however, the cause for decreased Ca concentration is unknown. Our objectives were to (1) describe Ca dynamics following an intravenous (IV) LPS challenge in early postpartum cows, and (2) compare inflammatory-induced changes in Ca dynamics between IV Ca-treated cows and control cows. Cows (n = 14, 8 ± 1 d in milk) were enrolled in a matched-pair randomized controlled design to receive IV Ca (IVCa) in a eucalcemic clamp for 12 h, or 0.9% NaCl (CTRL) following an IV LPS infusion (0.040 or 0.045 µg of LPS/kg of body weight over 1 h). During the 24 h following LPS infusion, circulating concentrations of parathyroid hormone and serotonin were measured, serum and urine samples were collected to calculate urinary fractional excretion of Ca (FECa), and fecal samples were collected to calculate Ca apparent digestibility (ADCa) using amylase-treated and ash-corrected undigested neutral detergent fiber after 240 h (uNDFom240) as an internal marker. Changes in Ca intake and milk Ca secretion were also quantified and compared with baseline values. Cows were fasted during challenge and dry matter intake was 20 ± 5% less than baseline values on the day of challenge and did not differ between groups. On the day of challenge, milk Ca concentration increased, but milk yield decreased such that total Ca secreted in milk did not change from baseline. Urine FECa was low overall, but an interaction of treatment and time was identified such that FECa increased in IVCa but decreased in CTRL. Concentrations of parathyroid hormone increased and serotonin decreased following challenge. Fecal dry matter decreased from baseline, but did not differ between 6, 12, and 24 h, and did not differ between groups. An interaction of treatment and time was identified for ADCa and apparent digestibility of dry matter such that digestibility was decreased in CTRL but not IVCa at 6 h. Acute immune activation induced hypocalcemia in CTRL, and although urinary Ca excretion was not a primary cause, it is unclear to what degree hypocalcemia was due to altered ADCa. Eucalcemia appeared to alter adaptations in Ca homeostasis during immune activation as FECa was increased in IVCa animals.

Relationship between blood calcium level and post-milking teat canal closure in dairy cows.

The teat canal-one of the primary defense mechanisms of the udder-ensures the milk flow during milking in bovines and prevents pathogens from entering the udder by forming a barrier through the elastic muscle and keratin layers tightly closing the surrounding area. The current study investigated the effects of blood calcium status on teat closure in cows after milking. The study covered 200 healthy teats, of which 100 were from normocalcemic (NC) cows and 100 were from subclinical hypocalcemic (SCH) cows. Teat canal length (TCL) and width (TCW) were measured with ultrasonography at 0-min pre-milking and 15- and 30-min post-milking. Cylindrically shaped teat canal volume (TCV) was calculated by deriving from TCL and TCW. Time-dependent changes in teat canal closure and their relationships with blood calcium levels were analyzed. The results showed that the calcium level did not affect TCL, TCW, and TCV (P > 0.05) during the 15-min post-milking period. However, TCL (P < 0.001), TCW (P < 0.05), and TCV (P < 0.001) were lower in NC cows than in SCH cows at 30-min post-milking. At 15-min post-milking, no correlation existed between the teat canal closure (ΔTCL, ΔTCW, and ΔTCV) and the blood calcium level, while significant correlations were available between the teat canal closure and the blood calcium level {ΔTCL (r: - 0.288, P < 0.001), ΔTCW (r: - 0.260, P < 0.001), ΔTCV (r: - 0.150, P < 0.05)} at 30-min post-milking. The current study concluded that the blood calcium status significantly impacts the teat canal closure in bovines, and calcium status should be meticulously monitored with the mastitis control program to apply necessary strategic steps.

Validation of a blood gas device for ionized calcium analysis in Holstein cows.

BACKGROUND: Accurate analysis of ionized calcium (iCa) is critical for the detection of hypocalcemia or subclinical hypocalcemia. The Edan i15 Vet (EDAN) blood gas device has not been validated for iCa in dairy cows. OBJECTIVES: We aimed to validate the EDAN blood gas device against the Gem Premier 3000 (GEM) analyzer by measuring iCa concentrations and evaluating the ability of these measurements, compared with serum total calcium (TCa) concentrations, to diagnose subclinical hypocalcemia. METHODS: iCa concentrations were measured with the EDAN and GEM devices, and serum TCa concentrations were measured with a wet biochemistry method with blood from 125 lactating Holstein cows between calving to day 27 postpartum. RESULTS: Bland-Altman plots showed a mean and total bias of 0.05 and 0.24 mmol/L for the EDAN device, respectively. The intercept did not include zero, but the slope included 1.0 in the Passing-Bablok regression. The sensitivity and specificity (Se/Sp) of the EDAN device were 93/94%, 93/90%, 91/93%, and 85/95% for iCa cut-off values of <1.00, 1.05, 1.10, and 1.15 mmol/L, respectively, as determined with the GEM device. The Se/Sp were 57/82% and 72/80% for EDAN and 57/80% and 72/79% for GEM at serum TCa cut-off points <2.15 and <2.00 mmol/L, respectively. The average iCa concentrations analyzed with the GEM and EDAN devices were 1.04 ± 0.18 and 1.09 ± 0.17, respectively. CONCLUSIONS: The EDAN device did not have satisfactory agreement with GEM and could not be used interchangeably, but it had satisfactory Se/Sp to diagnose subclinical hypocalcemia compared with the GEM-derived iCa cut-off points. Serum TCa concentration cut-off values were not suitable for diagnosing subclinical hypocalcemia because of unsatisfactory Se/Sp compared with iCa concentrations analyzed by the GEM and EDAN devices. The iCa values analyzed using the EDAN and GEM devices were consistent with previously reported data.

Effects of feeding rumen-protected methionine pre- and postpartum in multiparous Holstein cows: Health disorders and interactions with production and reproduction.

Study objectives were to evaluate the effects of feeding rumen-protected Met (RPM) in pre- and postpartum total mixed rations (TMR) on health disorders and the interactions of health disorders with lactation and reproductive performance. Multiparous Holstein cows [470; 235 cows at University of Wisconsin (UW) and 235 cows at Cornell University (CU)] were enrolled at approximately 4 wk before parturition and housed in close-up dry cow (n = 6) and replicated lactation pens (n = 16). Pens were randomly assigned to treatment diets (pre- and postpartum, respectively): (1) control (CON): basal diet = 2.30% and 2.09% Met as % of metabolizable protein (MP) (UW) or 2.22% and 2.19% Met as % of MP (CU); (2) RPM: basal diet fed with RPM with 2.83% and 2.58% Met (Smartamine M, Adisseo Inc.; 12 g prepartum and 27 g postpartum), as % of MP (UW) or 2.85% and 2.65% Met (Smartamine M; 13 g prepartum and 28 g postpartum), as % of MP (CU). Total serum Ca was evaluated at the time of parturition and on d 3 ± 1 postpartum. Daily rumination was monitored from 7 d before parturition until 28 d postpartum. Health disorders were recorded during the experimental period until the time of first pregnancy diagnosis (32 d after timed artificial insemination; 112 ± 3 d in milk). Uterine health was evaluated on d 35 ± 3 postpartum. Time to pregnancy and herd exit were evaluated up to 350 d in milk. Treatment had no effect on the incidence of most health disorders and did not alter daily rumination. Cows fed RPM had reduced subclinical hypocalcemia (13.6 vs. 22%; UW only) on day of parturition relative to CON. Percentage of cows culled (13.1 vs. 19.3%) and hazard of herd exit due to culling [hazard ratio = 0.65, 95% confidence interval (CI): 0.42-1.02] tended to be reduced for cows fed RPM compared with CON. Moreover, cows fed RPM had greater milk protein concentration and protein yield overall, although retrospective analysis indicated that RPM only significantly increased protein yield in the group of cows with one or more health disorders (1.47 vs. 1.40 kg/d), not in cows without health disorders (1.49 vs. 1.46 kg/d) compared with CON. Overall, treatment had no effect on pregnancy per timed artificial insemination; however, among cows with health disorders, those fed RPM had reduced time to pregnancy compared with CON (hazard ratio = 0.71, 95% CI: 0.53-0.96). Thus, except for subclinical hypocalcemia on the day of parturition, feeding RPM in pre- and postpartum TMR did not reduce the incidence of health disorders, but our retrospective analysis indicated that it lessened the negative effects of health disorders on milk protein production and time to pregnancy.

Surgical description and outcome of ultrasound-guided minimally invasive parathyroidectomy in 50 dogs with primary hyperparathyroidism.

OBJECTIVE: To describe the surgical technique and clinical outcome of minimally invasive parathyroidectomy for primary hyperparathyroidism (PHPT) in the dog. ANIMALS: Fifty client-owned dogs with PHPT that underwent minimally invasive parathyroidectomy. STUDY DESIGN: Retrospective cohort study. METHODS: An ultrasound-guided mini lateral approach was made via a plane established between the sternocephalicus muscle and sternohyoideus muscles to expose the thyroid gland and enlarged parathyroid gland. Abnormal parathyroid glands were removed en bloc via partial thyroidectomy. The technique for bilateral disease was similar, the skin incision was made on midline and moved laterally to develop the above-mentioned plane of dissection. Age, sex, breed, bodyweight, ultrasound findings, histopathological diagnosis, surgical time, preoperative clinical signs, and clinical outcome were extracted from the records for descriptive statistics. RESULTS: A total of 62 glands were surgically removed, including 17 hyperplastic glands (17/62, 27.4%), 34 adenomas (34/62, 54.8%), and two carcinomas (2/62, 3.2%). Hypercalcemia resolved shortly after surgery in 44 dogs (44/45, 97.8%). One dog had recurrent hypercalcemia (1/45, 2.2%), one dog had persistent hypercalcemia (1/45, 2.2%), two dogs had permanent hypocalcemia requiring life-long calcitriol supplementation (2/45, 4.4%), and one dog died from clinical hypocalcemia (1/45, 2.2%). CONCLUSION: Minimally invasive parathyroidectomy was associated with a low morbidity and led to favorable outcomes in 44/45 dogs in this series. CLINICAL SIGNIFICANCE: The results of this study supports the use of minimally invasive parathyroidectomy to treat PHPT in dogs.

Review: Dietary cation-anion difference to prevent hypocalcemia with emphasis on over-acidification in prepartum dairy cows.

Hypocalcemia remains a common metabolic disorder of dairy cattle; therefore, an efficient prevention is still challenging. Among the various prevention strategies for hypocalcemia is the use of anionic compounds to induce a mild metabolic acidosis during the prepartum period. Acid-base status can be readily assessed through urine pH. Accordingly, a target urine pH during the prepartum period between 6.0 and 6.8 has been recommended for Holstein cows; however, in several countries, including the US, certain nutritional strategies are still focused on benchmarking the urine pH to below 6.0. Unfortunately, over-acidification can have no advantages and/or detrimental effects on both the dam and her offspring. In this review, updated information regarding the use of anionic diets on prepartum dairy cows and the potential negative impact of such diets on both cow and calf performance are discussed. There is an urgent need for studies that will elucidate the pathophysiological mechanisms by which very acidotic diets may impact the well-being and productive efficiency of dairy cows, and the transgenerational effects of such diets on offspring performance and survival.