Effect of oxytocin infusion on luteal blood flow and progesterone secretion in dairy cattle

The objective of this study was to investigate the effects of oxytocin infusion on corpus luteum (CL) function during early to mid-diestrus by measuring luteal size (LS) and luteal blood flow (LBF) along with plasma levels of progesterone (P4) and prostaglandin metabolites (13,14-dihydro-15-keto-prostaglandin F2α, PGFM). On day (D) 7 of the estrus cycle (D1 = ovulation), seven cows received 100 IU of oxytocin (OXY) or placebo (PL) following a Latin square design. LS and LBF increased in both groups over time and no differences were observed between the groups. PGFM did not differ either within the groups over time or between the groups at any time point. P4 of the OXY group was higher compared to that of the the PL group 360 min after the infusion (p = 0.01) and tended to be higher at the time points 450 min, 48 h, and 72 h (all p = 0.08). Results from this study support the hypothesis that OXY is not directly involved in the mechanism(s) governing blood flow of the CL and has no remarkable effects either on luteal size or P4 and PGFM plasma levels. Further investigation is needed to elucidate the role of OXY in CL blood flow during early and late luteal phases

FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG)

To compare the efficacy and toxicity of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOXIRI) vs irinotecan and 5-FU/LV (FOLFIRI) as first-line treatment of patients with metastatic colorectal cancer (MCC). A total of 283 chemotherapy-naïve patients with MCC were enrolled (FOLFIRI arm: n=146; FOLFOXIRI arm: n=137). In the FOLFOXIRI arm, CPT-11 (150 mg m−2) was given on d1, L-OHP (65 mg m−2) on d2, LV (200 mg m−2) on days 2 and 3 and 5-FU (400 mg m−2 as i.v. bolus and 600 mg m−2 as 22 h i.v. continuous infusion) on days 2 and 3. In the FOLFIRI arm, CPT-11 (180 mg m−2) was given on d1 whereas LV and 5-FU were administered in the same way as in the FOLFOXIRI regimen. Both regimens were administered every 2 weeks. There was no difference in terms of overall survival (median OS: 19.5 and 21.5 months, for FOLFIRI and FOLFOXIRI, respectively; P=0.337), median time to disease progression (FOLFIRI: 6.9 and FOLFOXIRI: 8.4 months; P=0.17), response rates (33.6 and 43% for FOLFIRI and FOLFOXIRI, respectively; P=0.168). Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia (P=0.0001), diarrhoea (P=0.0001) and neurosensory toxicity (P=0.001) compared with patients treated with FOLFIRI. The present study failed to demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the observed median OS is one of the best ever reported in the literature

Body condition loss and increased serum levels of nonesterified fatty acids enhance progesterone levels at estrus and reduce estrous activity and insemination rates in postpartum dairy cows

Data from 96 Holstein Friesian cows on a commercial dairy farm were used to investigate whether body condition and serum levels of nonesterified fatty acids (NEFAs) postpartum (pp) affect progesterone (P4) levels, estrous activity, and fertility in dairy cows. The examination period started 14 days before the expected calving date and ended either when a cow was inseminated or at a maximum of 90 days pp. Body condition score (BCS; 1-5 scale) and backfat thickness (BFT) were determined every 2 weeks. Blood for analysis of NEFA and P4 concentrations was sampled weekly during the first 35 days pp and then every 48 hours until an ovulation was observed. Transrectal ultrasonography of the ovaries started at 21 days pp and was performed after blood sampling. If cows were not inseminated because of silent ovulation, sampling and ultrasonography continued on Days 7, 14, and 18 after ovulation and again every 48 hours until the next ovulation. Estrous activity was continuously measured with the Heatime estrus detection system. Pregnancy controls were performed ultrasonographically 28 and 42 days after AI. Cows with increased NEFA levels at 28 days pp had an increased risk of maintaining minimum P4 levels above 0.4 ng/mL at first recognized estrus (P = 0.03). Higher NEFA levels at Day 7 were associated with lower probability for a cow to have elevated P4 levels (≥2 ng/mL) by Day 35 pp, indicating delayed commencement of luteal activity (C-LA). Estrous activity was not influenced (P > 0.10) by minimum P4 concentrations at estrus, but more animals with C-LA until Day 35 pp showed estrous activity compared to cows without C-LA throughout this period (P = 0.006). Estrous activity was lower in cows with a low BCS 14 days pp (P = 0.02) and with a low BFT 42 days pp (P = 0.03). Moreover, the probability to exhibit estrus was reduced with higher NEFA levels at 21 days pp (P = 0.01). Eighty-five cows were inseminated and 37 (44%) got pregnant after insemination. Higher NEFA levels, especially 14, 28, and 42 days pp, were associated with lower probability to inseminate a cow. Regarding the cows that were inseminated, no influence of BCS, BFT, or NEFA levels on pregnancy per artificial insemination was found. In conclusion, cows with higher loss of body condition and elevated NEFA concentrations had higher P4 concentrations during estrus, a reduced estrous activity and insemination rate, but no depression in pregnancy per artificial insemination

Extended lactation in high-yielding dairy cows. I. Effects on reproductive measurements

The objective of this prospective field study was to evaluate the effects of extending the lactation period on various reproductive measurements of high-yielding Holstein cows. On 40 d in milk (DIM), cows were gynecologically examined (transrectal palpation, sonography, vaginoscopy). Cows without signs of clinical endometritis were blocked by parity and were randomly allocated to 1 of 3 experimental groups with a voluntary waiting period (VWP) of 40, 120, and 180 d, respectively (G40, n = 135; G120, n = 141; G180, n = 139). Cows of G120 and G180 were reexamined at the end of the VWP. If natural estrus was detected within 46 d after the end of the VWP, an artificial insemination was performed. If no estrus was detected, the respective cows were synchronized by applying the classical Ovsynch protocol. We found no difference in the proportion of cows in which estrus was detected between 40 to 86 DIM or in the days to first estrus between the 3 groups. Estrus detection in this period was lower in cows with body condition score <3 on 90 DIM compared with body condition score ≥3 (61.5 vs. 76.0%) and in cows with high energy-corrected milk production (ECM) on 92 DIM [58.6 vs. 70.1%, for cows with higher and lower than the median (39.9 kg) ECM, respectively]. The proportion of cows that estrus was detected within 46 d after the VWP was greater in G120 (88.9%) and G180 (90.8%) compared with G40 (70.4%). These effects were more apparent in cows with high ECM. The rate of estrus detection and of becoming pregnant in this period was greater for G120 (hazard ratio = 2.2 and 1.6, respectively) and for G180 (hazard ratio = 2.4 and 1.8) compared with G40. Cows in both groups with extended lactation had greater overall first service conception rates (G120 = 48.9%; G180 = 49.6%) and a lower number of services per pregnant cow (G120 = 1.56 ± 0.1; G180 = 1.51 ± 0.1) compared with G40 (36.6%; 1.77 ± 0.1). We observed no difference in pregnancy loss or in the proportion of cows culled up to 305 d of lactation between the 3 groups. The number of Ovsynch protocols per 1,000,000 kg of ECM was reduced by 75% in G180 and by 74% in G120 compared with G40 (5.9 vs. 7.1 vs. 25.1). In conclusion, extending the lactation of dairy cows can improve main reproductive measurements in high-yielding cows

Effect of Sugar Beet Pulp and Anionic Salts on Metabolic Status and Mineral Homeostasis during the Peri-Parturient Period of Dairy Sheep

Sugar beet pulp is a popular by-product of sugar extraction; however, it can potentially cause depletion of Ca availability due to its oxalic content. The experiment examined the effect of sugar beet pulp and anionic salts administration during the dry period on the serum concentration of calcium, magnesium, phosphate, and potassium of dairy sheep. Eighty-seven sheep were divided into three groups (A, B, and C) according to their body condition score (BCS) and age at 40 days before the expected lambing. All groups received alfalfa hay, mixed grass straw, and a concentrate supplement. The concentrate fed to groups B and C contained sugar beet pulp. The nutritional value fed to all three groups was similar, except for Dietary Cation Anion Difference (DCAD). Animals of group A had a DCAD of +198 mEq/kg, animals of group B of +188 mEq/kg, and animals of group C were fed 20 gr/d ammonium chloride to achieve a negative DCAD (−52 mEq/kg). All groups were fed the same ration after lambing. Blood samples were collected 30 d, 20 d, 17 d, 14 d, 10 d, 7 d, and 4 d before lambing (a.p.), 6 h, 12 h, 24 h, 7 d, 10 d, and 15 d after lambing (p.p) for calcium, magnesium, phosphate, and potassium, and 30 d a.p., 7 d, and 15 d p.p. for beta hydroxybutyrate acid (BHBA) concentrations. Urine samples were also collected 20 d, 10 d, 4 d a.p., and 7 d p.p for the evaluation of pH levels. Ca levels of the control group decreased earlier and were lower at 4 d a.p. compared to those of group B and C. Additionally, the control group showed lower p values compared to group C at 20 d and 17 d a.p. P levels recovered earlier post parturition in young (age 1–1.5 years old) compared to older ewes. Group C had lower urine pH values throughout the pre-parturient period, reflecting the acidifying effect of the administered ammonium chloride, without any side effect on macromineral blood concentration. Feeding sugar beet pulp and systemic acidifying before parturition is considered safe and might even be beneficial in preventing hypocalcemia

Multicenter phase II study of gemcitabine and oxaliplatin (GEMOX) as second-line chemotherapy in colorectal cancer patients pretreated with 5-fluorouracil plus irinotecan

Purpose: To evaluate the efficacy and tolerance of the gemcitabine/oxaliplatin (GEMOX) combination as second-line chemotherapy for patients with advanced colorectal cancer (CRC) pretreated with an irinotecan (CPT-11)/5-fluorouracil (5-FU)/leucovorin (LV) regimen. Patients and Methods: Patients with documented disease progression during or after first-line treatment with CPT-11 and 5-FU/LV were enrolled. Gemcitabine (1,000 mg/m(2) days 1 and 8) and oxaliplatin (100 mg/m2 day 1) were administered every 3 weeks. Results: Partial responses were observed in 6 of the 34 (17.7%) patients enrolled (intention-to-treat analysis; overall response rate: 17.7%; 95% confidence interval 4.8-30.5%). Eight (23.5%) patients experienced disease stabilization and 20 (59%) disease progression (tumor growth control rate = 41.2%). The median duration of response was 5.5 months, and the median time to tumor progression 2.7 months. The median overall survival was 9.1 months (1-year survival rate: 44.0%). Grade 3 neutropenia and thrombocytopenia occurred in 18 and 15% of the patients, respectively. Other severe non-hematologic toxicities were rare. Conclusion: The interesting tumor growth control rate and the favorable toxicity profile of the GEMOX regimen in pretreated patients with advanced CRC strongly suggest that this regimen may provide an alternative therapeutic option for this group of patients. Copyright (c) 2006 S. Karger AG, Basel

FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): A multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG)

To compare the efficacy and toxicity of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOXIRI) vs irinotecan and 5-FU/LV (FOLFIRI) as first-line treatment of patients with metastatic colorectal cancer (MCC). A total of 283 chemotherapy-naïve patients with MCC were enrolled (FOLFIRI arm: n = 146; FOLFOXIRI arm: n = 137). In the FOLFOXIRI arm, CPT-11 (150 mg m-2) was given on d1, L-OHP (65 mg m-2) on d2, LV (200 mg m-2) on days 2 and 3 and 5-FU (400 mg m-2 as i.v. bolus and 600 mg m -2 as 22 h i.v. continuous infusion) on days 2 and 3. In the FOLFIRI arm, CPT-11 (180 mg m-2) was given on d1 whereas LV and 5-FU were administered in the same way as in the FOLFOXIRI regimen. Both regimens were administered every 2 weeks. There was no difference in terms of overall survival (median OS: 19.5 and 21.5 months, for FOLFIRI and FOLFOXIRI, respectively; P = 0.337), median time to disease progression (FOLFIRI: 6.9 and FOLFOXIRI: 8.4 months; P = 0.17), response rates (33.6 and 43% for FOLFIRI and FOLFOXIRI, respectively; P = 0.168). Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia (P = 0.0001), diarrhoea (P = 0.0001) and neurosensory toxicity (P = 0.001) compared with patients treated with FOLFIRI. The present study failed to demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the observed median OS is one of the best ever reported in the literature. © 2006 Cancer Research UK