Increased serum serotonin improves parturient calcium homeostasis in dairy cows

Hypocalcemia in dairy cows is caused by the sudden increase in calcium demand by the mammary gland for milk production at the onset of lactation. Serotonin (5-HT) is a key factor for calcium homeostasis, modulating calcium concentration in blood. Therefore, it is hypothesized that administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, can increase 5-HT concentrations in blood and, in turn, induce an increase in blood calcium concentration. In this study, 20 Holstein dairy cows were randomly assigned to 2 experimental groups. Both groups received a daily i.v. infusion of 1 L of either 0.9% NaCl (C group; n = 10) or 0.9% NaCl containing 1 mg of 5-HTP/kg of BW (5-HTP group, n = 10). Infusions started d 10 before the estimated parturition and ceased the day of parturition, resulting in at least 4 d of infusion (8.37 ± 0.74 d of infusion). Until parturition, blood samples were collected every morning before the infusions, after parturition samples were taken daily until d 7, and a final sample was collected on d 30. Milk yield was recorded during this period. No differences between groups were observed for blood glucose, magnesium, and β-hydroxybutyrate. Cows receiving the 5-HTP infusion showed an increase in fatty acid concentrations from d ?3 to ?1 before parturition. Serum 5-HT concentrations were increased at d ?4 related to parturition until d 5 postpartum in the 5-HTP group compared with the C group. In addition, cows from the 5-HTP group had increased 5-HT concentrations in colostrum, but not in mature milk, on d 7 postpartum. Serum calcium concentrations decreased in both groups around parturition; however, calcium remained higher in the 5-HTP group than in controls, with a significant difference between groups on d 1 (1.62 ± 0.08 vs. 1.93 ± 0.09 mmol/L in control and 5-HTP groups, respectively) and d 2 (1.83 ± 0.06 vs. 2.07 ± 0.07 mmol/L in control and 5-HTP groups, respectively). Additionally, colostrum yield (first milking) was lower in the 5-HTP group compared with the C group, but without consequences on colostrum IgG concentrations. Milk yield did not differ between groups during the rest of the experiment. The study data were consistent with the concept that infusion of 5-HTP to dairy cows increases blood 5-HT concentrations, which in turn is a significant regulatory component in the chain of effectors that affect calcium status around parturition, hence the occurrence of clinical or subclinical hypocalcemia.     

Interaction of 5-hydroxy-l-tryptophan and negative dietary cation-anion difference on calcium homeostasis in multiparous peripartum dairy cows

Hypocalcemia affects almost 50% of all dairy cows. Our laboratory has previously demonstrated that infusions of the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP) increase circulating calcium concentrations in the Holstein transition cow. It is unknown whether feeding a negative dietary cation-anion difference (DCAD) diet alters the relationship between 5-HTP and hypocalcemia. The main objective of this study was to determine whether feeding a negative DCAD (?DCAD) diet before calving in conjunction with 5-HTP treatment could further diminish the magnitude of hypocalcemia at the time of calving. We used a randomized complete block design with a 2 × 2 factorial arrangement. Thirty-one multiparous Holstein cows were fed either a positive (+13 mEq/100 g) or negative (?13 mEq/100 g) DCAD diet 21 d before parturition and were intravenously infused daily with saline or 5-HTP (1 mg/kg) starting 7 d before the estimated date of parturition. Cows were blocked by parity and were randomly assigned to 1 of 4 treatment groups: positive DCAD plus saline, positive DCAD plus 5-HTP, negative DCAD plus saline, and negative DCAD plus 5-HTP, resulting in n = 8 per group. Total calcium (tCa), ionized calcium (iCa), and feed intake were recorded. The iCa was elevated prepartum in the ?DCAD/5-HTP group compared with the other treatment groups as well as on d 0 and 1 postpartum. Although differences in tCa were not significant across the pre- or postpartum periods, tCa was numerically higher on d 0 and significantly higher on d 1 in ?DCAD/5-HTP cows compared with all other groups. Prepartum the ?DCAD/5-HTP treatment group ate less than the other treatment groups; however, postpartum dry matter intake differences were not significant. These findings demonstrate that feeding a ?DCAD diet in conjunction with 5-HTP prepartum can increase postpartum circulating iCa concentrations and therefore diminish the magnitude of hypocalcemia at the time of parturition.     

Short communication: Effect of dietary phosphorus deprivation in late gestation and early lactation on the calcium homeostasis of periparturient dairy cows

Environmental concerns with P of animal origin polluting surface waters are leading to legal incentives aimed at reducing the dietary P content of dairy cow rations to the lowest possible level that does not negatively affect health and productivity. The objective of the present study was to determine the effect of feeding rations with low dietary P content in late gestation on the Ca homeostasis of the periparturient dairy cow. Eighteen multiparous dairy cows were either fed a P-deficient (0.15% P in dry matter antepartum and 0.20% P in dry matter postpartum) but otherwise balanced ration or a control ration with adequate P content (0.28% P in dry matter antepartum and 0.44% P in dry matter postpartum) during the last 4 wk of gestation until d 10 postpartum. Blood was obtained before initiation of P-deprivation (baseline) and ?10, ?2, +1, +3, and +10 d relative to parturition to be analyzed for plasma concentrations of Ca [Ca] and inorganic phosphate [Pi]. In addition, plasma concentrations of parathyroid hormone [PTH], the bone resorption marker CrossLaps [CTX], 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined in a subset of samples. Feeding a P-deficient diet for 4 wk antepartum positively affected the Ca homeostasis of periparturient cows. Clinical hypocalcemia occurred in 3/9 control and 0/9 P-deprived cows. [Calcium], [PTH], and plasma concentrations of vitamin D metabolites did not differ between groups until parturition, whereas [Pi] was decreased and [CTX] significantly increased in P-deprived animals. At parturition [PTH] was significantly greater in control cows compared with P-depleted cows. The P-deprived cows had significantly higher [Ca] than control cows on d +1 (2.46 ± 0.11 vs. 2.27 ± 0.41 mmol/L) and +2 (2.61 ± 0.13 vs. 2.35 ± 0.25 mmol/L). Plasma [CTX] was significantly higher in P-deprived than in control cows on d +2. Bone resorption and the typical increase in 1,25-dihydroxyvitamin D in periparturient P-deprived cows seemed to occur despite the smaller rise of [PTH], suggesting either greatly increased sensitivity to PTH or bone mobilization independent of PTH. Future studies must explore potentially negative effects of P-deprivation antepartum on health and productivity of the dairy cow in the following lactation.     

Short communication: Circulating serotonin (5-HT) concentrations on day 1 of lactation as a potential predictor of transition-related disorders

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.     

Short communication: Circulating serotonin is related to the metabolic status and lactational performance at the onset of lactation in dairy cows

Serotonin (5-hydroxytryptamine, 5-HT) affects many physiological functions because it is involved in glucose and lipid metabolism, calcium homeostasis, and regulation of lactation in dairy cows. This study aimed to examine physiological differences in serum 5-HT concentrations (high vs. low) and their association with metabolic status and milk production at the onset of lactation. Twelve multiparous Holstein dairy cows were milked within 4 h of calving, and blood and milk samples were collected at the first 6 subsequent milkings after parturition and at the evening milkings on d 5, 8, 10, and 14. Cows were retrospectively divided into 2 groups (6 cows/group): low serum 5-HT (LSS) and high serum 5-HT (HSS) according to their calculated areas under the curve (AUC) for serum 5-HT for the entire experimental period (cut-off: 46,000 ng/mL × 324 h). Concentrations of 5-HT, free fatty acids (FFA), β-hydroxybutyrate (BHB), glucose, calcium, and IGF-1 were measured in blood. Milk was analyzed for fat, protein, lactose, and 5-HT concentrations. Milk yield was recorded at each milking and energy-corrected milk yield was calculated. Serum 5-HT concentrations were higher in HSS than in LSS [AUC (ng/mL × 324 h): 57,830 ± 4,810 vs. 25,005 ± 5,930]. The amount of energy-corrected milk was lower in HSS than in LSS. The HSS group produced less colostrum and had decreased milk yield, specifically during the first 6 milkings. Concentrations of FFA, BHB, and glucose in plasma did not differ between groups. Concentrations of IGF-1 in serum were elevated in HSS compared with LSS throughout the experiment. Total circulating calcium concentrations in serum tended to be higher in HSS than in LSS. Milk fat and protein yields were decreased in HSS compared with LSS. Milk 5-HT decreased overall during the experimental period, with LSS maintaining higher 5-HT concentrations than HSS until d 14 of lactation. In conclusion, cows with high serum 5-HT concentrations showed a reduced metabolic load at the onset of lactation, concomitantly lower milk yield, and a reduced energy output via milk.     

Short communication: Mammary gland tight junction permeability after parturition is greater in dairy cows with elevated circulating serotonin concentrations

After parturition, the start of copious milk production in dairy cows requires the closure of tight junctions (TJ) to form the blood–milk barrier and prevent paracellular transfer of blood constituents into milk [e.g., lactate dehydrogenase (LDH) and serum albumin (SA)] and vice versa [e.g., appearance of α-lactalbumin (α-LA) in blood]. Serotonin (5-HT) has been demonstrated to alter tight junction permeability in the mammary gland. The present study investigated individual differences of TJ permeability of mammary epithelium at the beginning of lactation in relation to circulating 5-HT in dairy cows. Blood and milk samples were obtained from 11 multiparous Holstein dairy cows for the first time at 4 h after parturition, at the following 5 milkings, and at the evening milkings on d 5, 8, 10, and 14 of lactation. Retrospectively, cows were split into 2 groups according to their calculated areas under the curve of serum 5-HT during the entire experimental period: a high-serum 5-HT (HSS) group (5 cows) and a low-serum 5-HT (LSS) group (6 cows). The areas under the curve of serum 5-HT concentrations over the 324-h experimental period were 62 ± 2 × 10³ ng/mL in HSS and 25 ± 5 × 10³ ng/mL in LSS. Plasma α-LA concentration was greater in LSS than in HSS cows at the first milking, but no difference between groups was found from the second to sixth milking. Yield of α-LA in milk was lower in HSS than in LSS during the first 6 milkings postpartum, especially in colostrum. Concentrations of α-LA, IgG₁, and IgG₂ in milk did not differ between groups during the entire experiment except for higher IgG observed in LSS than in HSS at the second milking and for higher IgG₂ found in HSS compared with LSS on d 5. In contrast, SA concentrations and LDH activity in milk were lower in LSS compared with HSS cows during the first 6 milkings postpartum, particularly in colostrum. Milk somatic cell count was higher in HSS than in LSS throughout the study. Higher circulating 5-HT concentrations were associated with an increased transfer of the paracellularly transported SA, LDH, and somatic cell count, especially at the first milking, suggesting that 5-HT affects TJ permeability during closure of the blood–milk barrier at the onset of lactation. Furthermore, higher serum 5-HT concentrations were associated with a lower α-LA yield in milk. A consistent relationship with serum 5-HT concentrations was neither observed for the transfer of IgG₂ nor the primarily transcellular transport of IgG₁ during the first milkings after parturition.     

Peripartal propylene glycol supplementation and metabolism, animal health, fertility, and production in dairy cows

The effect of peripartal supplementation with concentrate enriched at 10% propylene glycol (PG) on metabolism, animal health, fertility, and milk production was studied using 234 cows from 8 dairy farms with production averages of 8019 to 10,656 kg/yr. The feeding schedule for the PG group (n=117) was as follows: 13 d antepartum: 1.5 kg/d (= 150 mL PG); 12 d antepartum until parturition: 3 kg/d (= 300 mL PG); 1 to 12 d postpartum: 1 kg/d (= 100 mL PG). Control cows (n=117) received the same concentrate without PG. From a subset of cows (PG: n = 43; control: n = 40), blood samples were collected at 6, 3, and 1 wk antepartum, 3 d antepartum, on the day of parturition, and 1, 3, 5, 7, 9, and 11 wk postpartum for the determination of nonesterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), insulin-like growth factor (IGF)-I, and activities of aspartate-aminotransferase (AST) and glutamate-dehydrogenase (GLDH). From another subset of cows (PG: n=11; control: n=10), blood samples were collected 1 wk antepartum, on the day of parturition, and 1 wk postpartum to determine immunophenotypical and functional parameters of blood neutrophils. From 1 wk antepartum to 1 d postpartum, concentrations of NEFA were significantly lower in cows receiving PG compared with controls. Also, concentrations of BHBA in cows receiving PG were significantly lower from 1 wk antepartum until 7 wk postpartum. Concentrations of IGF-I were significantly higher in the PG group, from 1 wk antepartum until 1 wk postpartum than in the control group. Activities of AST and GLDH did not differ between groups. Immunophenotypical and functional characteristics of blood neutrophils were not influenced by treatment nor were animal health, reproduction, or milk production. Although indicators of metabolic status were improved by peripartal use of PG-enriched concentrate, economic benefits are questionable for dairy farms with good nutritional programs, as economically important factors such as milk production, animal health, and fertility were not influenced.     

Short communication: Timing of first milking affects serotonin (5-HT) concentrations

Hormonal signals differentially regulate the timing of parturition, as well lactogenesis and, potentially, colostrum formation in the mammary gland. Non-neuronal serotonin (5-HT) is a homeostatic regulator of the mammary gland. In the current study, we manipulated the timing of first milking to investigate its effects on serum 5-HT and calcium concentrations in the maternal and calf circulation, as well as in colostrum. Twenty-three cows were randomly assigned to a control (CON; n = 10) group, milked for the first time at 4 h postcalving, or a treatment (TRT; n = 13) group, milked for the first time approximately 1 d before calving in addition to 4 h postcalving. Maternal blood samples were collected for 4 d precalving, 3 times daily, and 1 blood sample was taken 4 h postcalving. Calf blood samples were collected 4 (before first colostrum feeding) and 12 h after birth, and at 3 wk of age. Calves from both treatments were fed colostrum from their respective mothers. Serum 5-HT concentrations were greater in CON cows and decreased significantly in TRT cows after milking was initiated precalving (951 vs. 524 ± 111 ng/mL, respectively). Cow serum calcium concentrations were affected by time, beginning to decrease 1 d precalving until 4 h postcalving, but this drop in serum calcium was more pronounced in TRT cows. Serum 5-HT and calcium concentrations were negatively correlated (r = −0.57) for the CON cows and positively correlated (r = 0.6) for the TRT cows. Maternal calcium and 5-HT decreased similarly due to precalving milking. Calcium and 5-HT concentrations were greater in colostrum collected from TRT cows milked precalving. Overall, calves had higher circulating 5-HT concentrations than cows, and calves born to TRT cows had increased 5-HT concentrations compared with the CON. Precalving milking could affect 5-HT synthesis within the mammary gland and therefore affect maternal 5-HT and calcium concentrations. Further research is needed in ruminants to assess the extent of 5-HT placental transfer, its role on pre- and postnatal development of the calf, the importance of its presence in colostrum, and potential long-term effects on calf health.     

Short communication: Supplementation of colostrum and milk with 5-hydroxy-l-tryptophan affects immune factors but not growth performance in newborn calves

In ruminants, colostrum is the main source of immunoglobulins for the newborn animal, conferring immune protection until the immune system becomes active and able to synthesize its own immunoglobulins. Serotonin (5-HT), a biogenic amine derived from tryptophan, has stimulatory effects on many physiological processes, including components of the innate (mastocytes, eosinophils, and natural killer cells) and adaptive (T and B lymphocytes) immune systems. Based on the known effects of 5-HT on the immune system, we hypothesized that increased concentrations of 5-HT, through administration of its precursor 5-hydroxy-l-tryptophan (5-HTP), may positively affect development of the calf's immune system and therefore support health and growth performance during the first weeks of life. Eighteen calves were randomly assigned to 1 of 2 experimental groups (control and 5-HTP), resulting in n = 9 per treatment group. Both groups received 2 colostrum meals from a common pool of colostrum. Thereafter, calves were fed milk replacer twice daily for 30 d. In the 5-HTP group, colostrum and milk replacer were supplemented with 1.5 mg of 5-HTP/kg of birth weight during the first 15 d after birth. Body weight was recorded at birth and on d 5, 10, 15, and 30 after birth. Blood samples were collected every morning (0800 h) before feeding from birth until d 5 and then on d 7, 9, 11, 13, 15, and 30 after birth. Serum 5-HT concentrations were increased as a consequence of the 5-HTP supplementation. Plasma immunoglobulin G concentrations did not differ between groups throughout the experimental period. The blood mRNA abundance of several factors related to the innate and adaptive immune system [nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), serum amyloid A-1 (SAA1), chemokine C-C motif ligand 5 (CCL5), cyclooxygenase 2 (PTGS2), haptoglobin (HP), and IL-1β] were increased in calves supplemented with 5-HTP. Supplementation of 5-HTP did not affect any of the measured metabolites (fatty acids and glucose) or minerals (calcium and magnesium) or milk feed intake, feed conversion ratio, and growth. In conclusion, 5-HTP supplementation induced an increase of 5-HT concentrations in blood and caused an increase in mRNA abundance of several factors related to the innate and adaptive immune systems, which might increase the protection of the calf against external agents.     

Peripartal progesterone and prolactin have little effect on the rapid transport of immunoglobulin G into colostrum of dairy cows

Colostrum formation and lactogenesis in the mammary gland and the timing of parturition are regulated by endocrine signals. Changes in progesterone (P4) and prolactin (PRL) are considered key events that inhibit colostrum formation, trigger parturition, and signal the onset of lactation. The goal of our study was to determine if colostrum yield and composition and immunoglobulin transfer are affected by prepartum milking relative to the decrease in P4, peak of PRL, or occurrence of parturition. Twenty-three multiparous cows were randomly assigned to 1 of 2 groups: (1) control with first milking at 4 h postcalving (CON, n = 11), and (2) treatment group with first milking approximately 1 d before calving and second milking at 4 h after parturition (APM, n = 12). Colostrum yields were recorded and proportional samples were analyzed for immunoglobulin G (IgG) concentration. Blood plasma samples for the analyses of P4 and PRL were collected 3 times daily at 8-h intervals for 4 d prepartum and again taken at 4 h after parturition. Total colostrum mass of APM cows was higher than that of CON cows. Immunoglobulin G concentration and protein content did not differ between antepartum milking in APM cows and postpartum milking in CON cows. Colostrum IgG concentration and protein content in APM cows at the postpartum milking were lower compared with the IgG concentration established at the prepartum (APM) and postpartum milkings of CON cows. Immunoglobulin G mass did not differ in first and second colostrum collection in APM cows but was lower compared with that of CON cows. The sum of IgG mass in APM cows (prepartum + postpartum collections) did not differ from that of CON cows. Lactose and fat in milk (concentration and mass) increased from first to second milking in APM cows. Total mass of lactose and fat in APM cows (prepartum + postpartum collections) was greater compared with that of CON cows. The finding that the time of milking relative to parturition, P4 decrease, and PRL peak slightly affected yield and quality of colostrum emphasizes the complex interactions of numerous endocrine and morphological changes occurring during colostrogenesis and lactogenesis in dairy cows. The considerably rapid transfer of immunoglobulins into colostrum of prepartum-milked cows within a few hours leads to the hypothesis that the transfer of IgG can be very fast and—contrary to earlier findings—persist at least until parturition.     

Observation on the use of 1 alpha-hydroxyvitamin D3 in the prevention of bovine parturient paresis: the effect of a single injection on plasma 1 alpha-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, calcium, and hydroxyproline

Israeli Friesian cows in the third or later lactation, were injected intramuscularly with 1 alpha-hydroxyvitamin D3 in propylene glycol. Plasma 1 alpha-hydroxyvitamin D3 peaked 24 to 48 h after 700 micrograms of the drug was injected and decreased to the initial concentration 4 d later. The disappearance rate of 1 alpha-hydroxyvitamin D3 from the blood was .330 d-1 (biological half-life of 2.1 d). Plasma 1,25-dihydroxyvitamin D3 peaked 24 to 48 h after the injection and approached the initial concentration 5 to 7 d later. Plasma calcium increased within 24 h, reached a plateau at 4 to 6 d, and then decreased. Administration of 700 micrograms 1 alpha-hydroxyvitamin D3 resulted in higher plasma 1,25-dihydroxyvitamin D3 and calcium concentrations than when 350 micrograms of the drug was injected. 1 alpha-Hydroxyvitamin D3 did not affect plasma hydroxyproline. The injection of 700 micrograms 1 alpha-hydroxyvitamin D3 52 to 36 h before parturition resulted in a greater increase in plasma 1,25-dihydroxyvitamin D3 than that obtained with 350 micrograms. In both groups 1,25-dihydroxyvitamin D3 peaked 24 h after injection, as opposed to the controls, which peaked 72 h postpartum. At parturition, the 700-micrograms dose resulted in a slight hypercalcemia; the 350-micrograms dose moderated the hypocalcemia prevalent during this period, whereas in controls hypocalcemia was more pronounced. In cows injected with 700 micrograms, hypercalcemia was observed until the 15th d postpartum. Plasma hydroxyproline was elevated in all cows 48 to 72 h after parturition, but the increase was smaller in animals injected with 1 alpha-hydroxyvitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prepartal hormone administration on feed intake and mineral metabolism of cows.

Subcutaneous administration of progesterone (.25 mg/kg body weight per day) to mature cows from 14 days before projected parturition until parturition increased feed intake over control cows. Incidence of milk fever and plasma calcium, phosphorus, magnesium, and hydroxyproline were not significantly different between treated and control cows. Subcutaneous administration of estradiol-17beta (.05 mg/kg body weight per day) or oral administration of melengestrol acetate (1 mg/day) from 7 days before projected parturition date until parturition decreased feed intake over control cows. Milk fever incidence and absorption of calcium, phosphorus, and magnesium were not significantly different between treatment groups. Plasma calcium was not significantly different between treatment groups during either the prepartum or postpartal periods but tended to be higher postpartum in cows treated with estrogen.     

Effects of preventing periparturient hypocalcemia in cows by parathyroid hormone administration on hematology, conglutinin, immunoglobulin, and shedding of Staphylococcus aureus in milk

The effects of hypocalcemia at parturition on concentrations of serum immunoglobulin and conglutinin, number of bacteria shed into milk, and leukograms of dairy cows were investigated from -4 wk prepartum to 4 wk postpartum. Ten healthy multiparous Holstein cows were fed a high calcium diet to induce hypocalcemia at parturition. Five cows received intramuscular parathyroid hormone to prevent hypocalcemia at parturition. All cows experienced a leukopenia (attributable to an absolute and relative neutropenia) during the 1st wk after calving, decreased serum conglutinin activity during the first 3 wk postpartum, and decreased concentration of serum IgG1 during the 3 wk before calving. At parturition, a large increase in organisms was found in foremilk (1000 to 10,000 times more than prepartum values). Neither the hematological changes nor the decreased immunoglobulin concentration was influenced by hypocalcemia or the development of milk fever. This implies that the degree of hypocalcemia observed did not have a large or irreversible influence on bacterial infection, hematological, or humoral immunity changes in periparturient cows.     

Parenteral administration of glutamine modulates acute phase response in postparturient dairy cows

The objective of this study was to investigate whether administration of l-Gln would affect mediators of acute phase response in postparturient dairy cows. Twenty-four multiparous Holstein cows were blocked by the expected day of calving and randomly assigned to 1 of the 3 treatment groups (n = 8/group): 1) i.v. infusion of 10 L of 0.85% NaCl (control), 2) i.v. infusion of 106, or 3) 212 g/d of l-Gln mixed with 10 L of 0.85% NaCl solution; each treatment was given 8 h/d for each of 7 consecutive days starting on d 1 after calving. Blood samples were collected 1 wk before the expected day of parturition as well as on d 0, 7, 14, and 21 after parturition; plasma concentrations of serum amyloid A (SAA), haptoglobin, and lipopolysaccharide-binding protein were measured by ELISA, and α₁-acid glycoprotein was assessed by radial immunodiffusion. Concentrations of SAA, haptoglobin, and α₁-acid glycoprotein increased in control cows after parturition, reaching peak values on d 0 or 7 postpartum (60, 1,093, and 963 μg/mL, respectively). Cows infused with 106 g/d of l-Gln had greater concentrations of SAA in plasma on d 14 and 21 compared with controls (62.8 vs. 30.2 and 71.1 vs. 34.5 μg/mL, respectively). Cows infused with 212 g/d of l-Gln had greater concentrations of SAA on d 7 (82.5 vs. 53.9 μg/mL) and lower concentrations of haptoglobin on d 14 and 21 postpartum compared with controls (264 vs. 621 and 175 vs. 587 μg/mL, respectively). Cows treated with 106 and 212 g/d of l-Gln had greater plasma lipopolysaccharide-binding protein concentrations on d 7 compared with control group (50.0 and 35.6 vs. 10.8 μg/mL, respectively). There were no treatment differences with respect to milk yield and DM intake during the experimental period. In conclusion, our data indicate that i.v. administration of l-Gln modulated acute phase mediators in dairy cows after parturition and warrants further research into the mechanisms behind these effects.     

Feed restriction to induce and meloxicam to mitigate potential systemic inflammation in dairy cows before calving

Most dairy cows experience a transient decrease in feed intake in the 1 to 2 wk before calving, which has been associated with systemic inflammation (SI), indicated by increased blood haptoglobin (Hp) concentration. We aimed to characterize the association between prepartum decrease in feed intake and the onset of SI and, if present, the ability of meloxicam (MEL), a non-steroidal anti-inflammatory drug, to mitigate SI. Holstein cows (n = 45) were assigned to control (n = 13), feed restriction (FR) untreated (FR-U; n = 15), and FR treated with MEL (FR-T; n = 17) groups. Daily feed intake was measured from ?22 d from expected parturition until 35 d postpartum. Control cows were fed ad libitum, whereas FR-U and FR-T cows were reduced to 60% of their average intake for 4 consecutive days (?15 to ?12 d from expected calving). The FR-T cows received MEL (0.5 mg/kg of body weight) once daily for 4 consecutive days (?13 to ?10 d from expected calving). Blood samples were collected ?22, ?15, ?14, ?13, ?12, ?10, ?7, ?5, ?3, 0, 1, 3, 5, 7, 15, 22, and 35 d relative to calving to measure serum concentrations of total calcium, total protein, albumin, globulin, cholesterol, urea, glucose, gamma-glutamyl transferase, aspartate aminotransferase, glutamate dehydrogenase, β-hydroxybutyrate, nonesterified fatty acids, Hp, and insulin-like growth factor-1. Serum concentrations of lipopolysaccharide-binding protein were measured ?22, ?15, ?14, ?13, ?12, and ?10 d from expected calving. Simplified glucose tolerance tests were performed on ?15, ?12, ?5, 1, and 5 d relative to calving. Mixed linear regression models were used to assess the effects of FR and MEL on each metabolite. The interaction between treatment group and blood sampling day was forced into each model. All models accounted for body condition score, parity, and the cow as a random effect. Nonesterified fatty acids concentrations in both the FR-U and FR-T groups significantly increased from the second until the last day of FR. Feed restriction increased urea concentrations compared with the control group on ?14 d but decreased urea concentrations on ?10 d from expected calving. Control cows had greater β-hydroxybutyrate concentrations compared with FR cows on 15, 21, and 35 d postpartum. For all other metabolites, no differences were found. This model of FR produced substantial fat mobilization but based on serum Hp and lipopolysaccharide-binding protein concentrations did not generate measurable SI; therefore, we were unable to evaluate the ability of MEL to mitigate SI.     

Effects of peripartum propylene glycol or fats differing in fatty acid profiles on feed intake, production, and plasma metabolites in dairy cows

Dry multiparous cows were used to investigate the effects on intake, production, and metabolism of either a supplement containing 55% dry propylene glycol (PGLY), a prilled fat supplement (PrFA) containing a low proportion of unsaturated fatty acids (FA), or calcium soaps of FA supplement (CaLFA) containing a high proportion of unsaturated FA. Fifty-three dry cows (256 d pregnant) were stratified into 4 groups and began one of the following dietary treatments: 1) control cows were fed a dry cow diet and at postpartum were fed a lactating cow diet; 2) diets of cows in the PGLY group were supplemented with 500 g/d per cow of dry PGLY until 21 d in milk (DIM); 3) diets of cows in the PrFA group were supplemented with 230 g/d per cow of PrFA until 100 DIM; 4) diets of cows in the CaLFA group were supplemented with 215 g/d per cow of CaLFA until 100 DIM. Prepartum DMI was lower in the PrFA and CaLFA groups than in the control and PGLY groups, whereas postpartum DMI in the PrFA group was higher than that in the control group. Milk production until 100 DIM in both fat-supplemented groups was 4.5% higher than that in the control group. Plasma glucose concentrations pre- and postpartum were higher in the PGLY group than in the PrFA and CaLFA groups, but were similar to those in the control group. Prepartum nonesterified FA (NEFA) concentrations in plasma were increased by 43 and 70% in the PrFA and CaLFA groups, respectively, as compared with the control and PGLY groups. Both fat supplements increased plasma β-hydroxybutyrate concentrations over those of the PGLY and control groups pre- and postpartum. Peripartum plasma insulin concentrations in the control group were 1.7-fold higher than in the PrFA group and 2.1-fold higher than in the CaFA group. Differences between the PrFA and CaLFA groups were observed: DMI was higher pre- and postpartum in the PrFA group than in the CaLFA group, and prepartum plasma NEFA concentrations were 19% higher and insulin concentrations were 21% lower in the CaLFA group than in the PrFA group. No significant differences were observed in DMI, plasma glucose, NEFA, and β-hydroxybutyrate concentrations between the control and PGLY groups. Feeding fat to cows during late pregnancy decreased the DMI and negatively affected the metabolic status of the cows, as reflected by plasma metabolites. Furthermore, protected fat with a high proportion of unsaturated FA (CaLFA) was more pronounced in increasing plasma NEFA concentrations and depressing plasma insulin concentrations than fat with a low proportion of unsaturated FA (PrFA).     

Production and metabolic responses of periparturient Holstein cows to dietary conjugated linoleic acid and trans-octadecenoic acids

Thirty-eight multiparous Holstein cows were utilized in a completely randomized design to examine the effect of feeding calcium salts of conjugated linoleic acid (CLA) and trans-octadecenoic acids (trans-C18:1) on animal performance and lipid and glucose metabolism during the transition to lactation. Dietary treatments were initiated approximately 28 d prior to expected calving dates and continued through d 49 postpartum. Prepartum treatments consisted of 1) a basal diet (Control), 2) basal diet + 150 g/d of CLA mix (CLA), and 3) basal diet + 150 g/d of trans-C18:1 mix (TRANS). Amounts of calcium salts of CLA and trans-C18:1 mixes were adjusted to 225 g/d during the 49-d postpartum treatment period. All diets were offered as a total mixed ration. Prepartum fat supplementation had no detectable effects on dry matter intake, body weight, or body condition score. After parturition, cows in the TRANS group consumed less dry matter at wk 4, 5, and 6 of lactation than did cows in the control group. Cows fed the trans-C18:1 supplement were in a more severe negative energy balance than those fed the control diet at 1 wk of lactation. Periparturient fat supplementation had no detectable effects on milk yield during wk 1 to 7 of lactation. Milk fat was not affected during wk 1 to 4, but was reduced after wk 4 of lactation by dietary CLA. Feeding calcium salts of CLA decreased short- to medium-chain fatty acid (C4 to C14) concentrations and increased both linoleic and linolenic acid concentrations in milk fat. Concentrations of nonesterified fatty acids and beta-hydroxybutyric acid in blood were greater in cows fed the CLA-supplemented diet than in those fed the control diet at 1 wk of lactation. In spite of small numerical tendencies, hepatic lipid and triacylglycerol concentrations did not vary significantly among dietary treatments. Periparturient fat supplementation had no detectable effects on plasma glucose and insulin concentrations. Steady-state concentrations of hepatic mRNA encoding pyruvate carboxylase and phosphoenolpyruvate carboxykinase were greater for the TRANS treatment group than the control and CLA groups. Results indicate that dietary CLA and trans-C18:1 fatty acids may affect lipid and glucose metabolism in early postpartum Holstein cows through distinct mechanisms.     

Serum folates in gestating and lactating dairy cows

In Experiment 1, 70 cows were distributed in five groups of 14 animals each. Each group represented one physiological stage: parturition, 2 mo postpartum, 3 mo of gestation, 6 mo of gestation, and drying off at approximately 2 mo before parturition. Plasma volume, concentration of serum folates, and total serum folates were measured at each stage. In Experiment 2, four doses of folic acid (40, 80, 160, and 320 mg) were administered by intramuscular injection to four groups of 5 cows in late gestation and four groups of 5 cows in early lactation. Serum folates in all cows and milk folates in lactating cows were determined before injection of folic acid and on d 1, 2, 4, 8, and 16 after injection. In Experiment 1, plasma volume did not differ between physiological stages, but total serum folates increased from parturition to reach a peak value 2 mo later; thereafter, serum folates decreased from 3 mo of gestation to parturition. In Experiment 2, during late gestation, serum folates increased after injection of folic acid and reached the highest concentration with the dose of 160 mg. However, during early lactation, injection of folic acid had no effect on concentrations of serum or milk folates. Therefore, total serum folates decreased by 40% from 2 mo postpartum (around mating) to parturition. Moreover, at the end of gestation, serum folates can be increased by an intramuscular injection of folic acid. This may be an indication of an increased need for folic acid during gestation of dairy cows.     

Effects of induced parturition and estradiol on feed intake, liver triglyceride concentration, and plasma metabolites of transition dairy cows.

The effect of induced parturition and estradiol on feed intake, liver triglyceride, plasma metabolites, and milk yield was evaluated in fifty-six Holstein cows and heifers. Cows were assigned to treatments on d 260 of gestation and were on trial until d 10 postpartum for measurement of dry matter intake (DMI), plasma metabolites, and liver triglyceride and until d 31 postpartum to measure milk yield. Fourteen animals per group (9 cows and 5 heifers) received either a placebo, 1 mg of fenprostalene, 50 mg of estradiol-17 beta benzoate, or both on d 276 of gestation. Cows that received fenprostalene consumed more dry matter (DM) for the last 8 d prepartum than did cows that did not receive fenprostalene (9.6 kg/d vs. 8.5 kg/d, respectively) but consumed less DM for the first 10 d postpartum (10.9 kg/d vs. 13.1 kg/d, respectively). Cows injected with estradiol-17 beta benzoate tended to consume less DM postpartum than did cows not injected with estradiol-17 beta benzoate (11.3 kg/d vs. 12.7 kg/d, respectively). There was no effect of treatment on milk yield; however, a fenprostalene by day interaction resulted from lower milk yield on d 3, 4, 5, 7, and 10 relative to calving in cows that received fenprostalene. Administration of fenprostalene resulted in a delay in the peak plasma nonesterified fatty acid (NEFA) concentration until 2 d after calving. Plasma glucose concentrations were greatest 1 d prior to calving for cows that received fenprostalene, whereas plasma glucose concentrations peaked on the day of calving for cows that did not receive fenprostalene. Liver triglyceride increased over time; however, there was no effect of treatment on liver triglyceride. Calving induction improved DMI for the last 8 d prepartum, but a concomitant decrease in liver triglyceride after calving did not result. Estradiol-17 beta benzoate had no effect on plasma metabolites or liver triglyceride, indicating that the physiological rise in estradiol prior to calving does not have a primary role in lipolysis or hepatic fatty acid metabolism in the dairy cow.     

Prolonged,low-grade inflammation in the first week of lactation: Associations with mineral,protein, and energy balance markers,and milk yield,in a clinically healthy Jersey cow cohort

Our objectives were to perform a proof-of-concept study to assess the association of a prolonged inflammatory state (based on a continually elevated haptoglobin concentration at the end of the first week after parturition) with mineral, protein, and energy balance markers in the first 2 wk after parturition, and milk production in the first 60 d of lactation in clinically healthy cows. We conducted a cohort study in 1 herd in west Texas that was milking Jersey and Jersey–Holstein crosses. Only multiparous Jersey cows were eligible for enrollment. Cows were classified as having or not having elevated haptoglobin concentrations based on plasma concentrations evaluated on d 4 and 7 postpartum. We used median concentrations of haptoglobin in the reference population (i.e., before the exclusion of cows diagnosed with clinical diseases) as the limits for categorizing cows into 2 groups: cows with plasma haptoglobin concentrations greater than the median values on both d 4 (0.49 g/L) and 7 (0.35 g/L) had continually elevated haptoglobin (with eHp); and cows with plasma haptoglobin concentrations lower than or equal to the median values of the reference population on d 4 or 7 did not have continually elevated haptoglobin (without eHp). Next, cows with clinical diseases in the first 2 wk of the postpartum period were excluded, so that 233 cows remained for the final analyses. Evaluated outcomes were average daily milk production across the first 60 d of lactation, plasma Ca, Mg, and glucose concentrations on d 1, 2, 3, 4, 5, 7, 10, and 14 postpartum, and β-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), fructosamine, albumin, urea, and creatinine concentrations on d 3, 5, 7, 10, and 14 postpartum. Rectal temperatures measured on d 4, 7, and 10 postpartum were also analyzed. We performed statistical analyses using linear mixed models while accounting for the repeated effect of sampling time (plasma analytes and rectal temperature models) and weekly milk test (milk production model). Cows with eHp had lower plasma Ca concentrations in the first 2 wk after calving, but no differences in Mg, BHB, NEFA, glucose, or rectal temperatures compared to cows without eHp. Cows with eHp had lower plasma fructosamine, albumin, and urea concentrations in a time-dependent manner. They also had lower milk production (2.3 kg/d less than cows without eHp in the first 60 DIM). Our study demonstrated that 25% of cows without clinical disorders in the first 2 wk after parturition had continually elevated haptoglobin concentrations at d 7 after parturition relative to d 4, suggestive of a prolonged, low-grade systemic inflammatory state. More observational studies are needed to more fully characterize the duration of prolonged postpartum subclinical inflammation in cows without clinical diseases, as well as its long-term effects, and to evaluate the use of other potential markers of systemic inflammation to describe this disorder.