Low blood glucose concentrations after calving are associated with infertility in postpartum dairy cows perhaps because glucose is a master regulator of hormones and metabolites that control reproductive processes. The hypothesis was that low blood glucose postpartum is caused by inadequate glucose entry rate relative to whole-body demand as opposed to the alternative possibility that postpartum cows have a lower regulatory set point for blood glucose. Eight early postpartum (10 to 25 d) dairy cows (5 Holstein and 3 Guernsey) were jugular catheterized. During the first 24 h, cows were infused with physiological saline at 83.3 mL/h. After 24 h, the infusion solution was switched to 50% dextrose that was infused at a rate of 41.7 mL/h (total daily glucose dose=500 g). On d 3 and d 4, the rate of glucose infusion was increased to 83.3 mL/h (daily dose=1,000 g) and 125 mL/h (daily dose=1,500 g), respectively. On d 5, physiological saline was infused at 83.3 mL/h. Blood was sampled hourly through a second jugular catheter (contralateral side) and analyzed for glucose, nonesterified fatty acids, β-hydroxybutyrate, insulin-like growth factor 1, and insulin. Blood glucose concentrations on d 1 (saline infusion) averaged 53.4±1.7 mg/dL. Blood glucose concentrations increased on d 2 when cows were infused with 500 g/d and increased further on d 3 when cows were infused with 1,000g of glucose/d. Increasing the infusion rate to 1,500 g/d on d 4 did not cause a further increase in blood glucose concentrations. Based on a segmented regression analysis, the upper physiological set point for blood glucose was 72.1 mg/dL. Both insulin and insulin-like growth factor 1 concentrations increased in response to glucose infusion and decreased when cows were infused with saline on d 5. Serum nonesterified fatty acids and β-hydroxybutyrate concentrations decreased in response to glucose infusion and rebounded upward on d 5 (saline infusion). In conclusion, early postpartum cows had circulating blood glucose concentrations that were well below the upper set point defined in this study (72.1 mg/dL). Infusing approximately 1,000 g of glucose daily increased blood glucose to the physiological set point and rapidly changed the hormonal and metabolic profile that typifies postpartum cows. The inability of the early postpartum cow to achieve an adequate entry rate for glucose relative to whole-body demand is a possible mechanism that links postpartum physiology and nutrition to reproduction in dairy cows.
Timed artificial insemination (AI) programs have increased reproductive efficiency in dairy herds. A low timed AI pregnancy per AI is partially explained by cows that fail to respond optimally to the series of treatments that are designed to synchronize ovulation for AI. We hypothesized that testing cows for plasma progesterone concentrations during a timed AI protocol could be used as an early diagnostic test for nonpregnancy. Lactating Holstein cows (n=160) in 2 confinement-style dairies were used. Cows were treated with Presynch Ovsynch 56 for timed AI. Concentrations of progesterone in plasma were measured at -3, 0, 7, and 25 d relative to timed AI. Progesterone data were analyzed and receiver operating characteristic curves were generated by using logistic regression. The area under the receiver operating curves for a progesterone test for nonpregnancy on d -3 (PGF2α), 0 (AI), 7, and 25 d relative to timed AI were 0.68, 0.52, 0.55, and 0.89, respectively. The cutpoints and sensitivity (respectively) for the progesterone test were 0.51ng/mL (lower=nonpregnant) and 28.2% for the day of PGF2α, 0.43ng/mL (greater=nonpregnant) and 17.9% for the day of AI, 1.82ng/mL (lower=nonpregnant) and 23.1% for 7 d after AI, and 2.67ng/mL (lower=nonpregnant) and 76.0% for 25 d after AI. The false positive rate was less than 5% for all tests. Analysis of a second data set from a published study gave approximately the same cutpoints and sensitivity. When both studies were combined, approximately 20% of nonpregnant cows could be identified with a single test that was done before or shortly after AI with a false positive rate of less than 5%. When 2 and 3 tests were applied sequentially, the sensitivity for identifying nonpregnant cows increased from 38.4 to 50.5%. The pregnancy per AI for those cows that met the established progesterone criteria was approximately 3 to 4 times greater than those that failed to meet the criteria. The conclusions were that cows destined to be nonpregnant after timed AI can be identified before or shortly after AI. Testing for nonpregnancy before or shortly after AI may have utility with respect to eliminating a nonproductive AI (cows identified before AI) or shortening the time to reinsemination (cows identified by 1 wk after AI).
1 Drugs that inhibit TxA 2 synthesis are used to reduce platelet aggregation. The aim of this study was to compare the eects of a cyclo-oxygenase (COX) inhibitor (acetylsalicylic acid, ASA), a thromboxane synthetase (TxS) inhibitor (dazoxiben) and a dual TxS inhibitor and TxA 2 receptor blocker (DT-TX 30) on platelet aggregation and the platelet-subendothelium interaction in¯ow conditions. 2 The techniques used in this in vitro study were platelet aggregometry in whole blood, and measurement of platelet thromboxane B 2 and prostaglandin E 2 production and leucocyte production of 6-keto-PGF 1a . The platelet-subendothelium interaction was evaluated in rabbit aorta subendothelium preparations exposed to¯owing blood at a shear stress of 800 s 71. Morphometric methods were used to calculate the percentage of subendothelium occupied by platelets. 3 The 50% inhibitory concentration (IC 50 ) of DT-TX 30 in whole blood was in the range of 10 77 mM (induced with collagen or arachidonic acid) to 10 75 mM (induced with thrombin) or 10 74(induced with ADP). IC 50 values under all experimental conditions were lower with DT ± TX 30 than with ASA. For thromboxane B 2 the IC 50 were: ASA 0.84+0.05 mM, dazoxiben 765+54 mM, DT ± TX 30 8.54+0.60 mM. Prostaglandin E 2 was inhibited only by ASA (IC 50 1.21+0.08 mM). Leucocyte 6-keto-PGF 1a was inhibited by ASA (IC 50 6.58+0.76 mM) and increased by dazoxiben and DT ± TX 30. The greatest reduction in percentage subendothelial surface occupied by platelets after blood perfusion was seen after treatment with DT ± TX 30 in the range of concentrations that inhibited collagen-induced platelet aggregation (control group: 31.20+3.8%, DT-TX 30 at 0.1 mM: 10.71+0.55%, at 1.0 mM: 6.53+0.44%, at 5.0 mM; 1.48+0.07%). All three drugs reduced thrombus formation, although ASA (unlike dazoxiben or DT ± TX 30) increased the percentage surface occupied by adhesions. 4 In conclusion, the eect of speci®c blockage of TxS together with blockage of membrane receptors for TxA 2 can surpass the eect of ASA in inhibiting the platelet-subendothelium interaction in¯ow conditions.
Progesterone-containing controlled internal drug release (CIDR) inserts are used to synchronize the estrous cycle before PGF2α is administered for timed AI (14dCIDR-PGF2α program). The program, initially designed for beef cattle, was recently shown to be efficacious in dairy heifers. We hypothesized that the 14-d CIDR treatment would synchronize the estrous cycle in dairy heifers and result in a uniformly sized corpus luteum (CL) and largest follicle (LF) at the time of PGF2α treatment. Holstein (n=110) or Holstein × Guernsey (n=4) dairy heifers were assigned to 2 treatments: (1) 14dCIDR-PGF2α [CIDR in for 14 d, CIDR out for 16d, PGF2α and AI after observed estrus (n=57)] or (2) control [PGF2α and AI after observed estrus (n=57)]. Regardless of treatment, additional PGF2α injections were administered at 14-d intervals to heifers that were not seen in estrus. Ovarian ultrasonography and blood sampling were done on d 0 (CIDR administered), 14 (day CIDR removed), 19 (5d after CIDR removed), 30 (PGF2α administered), and 44 (second PGF2α dose administered to heifers that were not detected in estrus after the first PGF2α). Compared with control (untreated), more CIDR-treated heifers were categorized as having a small CL (≤ 9.9 mm) and large LF (15.0-19.9 mm) on d 14 (CIDR removal) and, as expected, a greater percentage of CIDR-treated heifers were in estrus during the 5d after the CIDR removal compared with control heifers (75.4 vs. 22.8%, respectively). On d 19, the CIDR-treated heifers had apparently ovulated based on disappearance of LF and appearance of small CL. On d 30 (PGF2α administration), 89% of 14dCIDR-PGF2α heifers had CL that were ≥ 20 mm in diameter compared with 55% for control. Presence of larger CL on d 30 was associated with greater concentrations of plasma progesterone in 14dCIDR-PGF2α compared with control (10.5 ± 0.5 vs. 5.0 ± 0.6 ng/mL, respectively). The percentages of heifers with LF in the smallest category (≤ 9.9 mm) tended to be less (5.3 vs. 16.6%) and the percentage of heifers with LF in the medium-size category (10.0 to 14.9 mm) tended to be greater (84.2 vs. 69.1%) for 14dCIDR-PGF2α versus control, respectively, on d 30. More heifers were detected in estrus within 5d after the first PGF2α (86.0 vs. 56.1%) and conception rate to AI using sexed semen tended to be greater (61.2% vs. 40.6%) for 14dCIDR-PGF2α compared with control (respectively). Treating dairy heifers with a CIDR for 14 d was an effective method to synchronize an estrous cycle before PGF2α was administered.
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