The Effect of A PRID®Delta-Based Estrus Synchronization Protocol On Pregnancy Rates In Cows With No Estrus Symptoms

The present study aimed to determine the effects of progesterone-based gonadotropin-releasing hormone (GnRH), prostaglandin F2α (PGF2α), and equine chorionic gonadotropin (eCG) injections on progesterone profiles and pregnancy rates in cows with no estrus symptoms within 60 days after parturition. A total of 80 cows were included in the study. All animals had the progesterone-releasing device PRID®Delta placed intravaginally for nine days with an injection of GnRH. On the eighth day, PGF2α was injected, and PRID®Delta was removed from the vagina on day nine. Artificial insemination was carried out 60 hours after PRID®Delta removal. In half of the animals (n = 40), 600 IU of eCG was injected when PRID®Delta was removed on the ninth day before artificial insemination 60 hours later. Blood samples were taken from the tail vein on days 0 and 8 to determine progesterone levels. The pregnancy rate in the group that received eCG was 37.5%, while it was 27.5% in those that did not (P = 0.4). While the dominant follicle diameter was 15.5 mm in cows injected with eCG during timed artificial insemination, the follicle diameter was 12.4 mm in cows with no eCG injection (P <0.001). There were no differences in serum progesterone values in blood samples taken until the time of artificial insemination. However, progesterone values in the blood taken during artificial insemination were 0.94 ng/ml in the eCG- group and 0.72 ng/ml in the eCG+ group (P <0.05). As a result, it was determined that eCG injections, in addition to progesterone-based GnRH and PGF2α applications, increased the pregnancy rates in cows without symptoms of estrus. The dominant follicle diameter was larger in cows treated with eCG during artificial insemination; however, follicle size did not increase the pregnancy rate.

8-Isoprostanes and Asymmetric Dimethylarginine as Predictors of Mortality in Patients Following Coronary Bypass Surgery: A Long-Term Follow-Up Study

Background: We previously demonstrated that enhanced oxidative stress and reduced nitric oxide bioavailability are associated with unfavorable outcomes early after coronary artery bypass grafting. It is not known whether these processes may impact long-term results. We sought to assess whether during long-term follow-up, markers of oxidative stress and nitric oxide bioavailability may predict cardiovascular mortality following bypass surgery. Methods: We studied 152 consecutive patients (118 men, age 65.2 ± 8.3 years) who underwent elective, primary, isolated on-pump bypass surgery. We measured plasma 8-iso-prostaglandin F2α and asymmetric dimethylarginine before surgery and twice after surgery (18–36 h and 5–7 days). We assessed all-cause and cardiovascular death in relation to these two biomarkers during a mean follow-up time of 11.7 years. Results: The overall mortality was 44.7% (4.7 per 100 patient-years) and cardiovascular mortality was 21.0% (2.2 per 100 patient-years). Baseline 8-iso-prostaglandin F2α was associated with cardiovascular mortality (HR 1 pg/mL 1.010, 95% CI 1.001–1.021, p = 0.036) with the optimal cut-off ≤ 364 pg/mL for higher survival rate (HR 0.460, 95% CI 0.224–0.942, p = 0.030). Asymmetric dimethylarginine > 1.01 μmol/L measured 18–36 h after surgery also predicted cardiovascular death (HR 2.467, 95% CI 1.140–5.340, p = 0.020). Additionally, elevated 8-iso-prostaglandin F2α measured at the same time point associated with all-cause mortality (HR 1 pg/mL 1.007, 95% CI 1.000–1.014, p = 0.048). Conclusions: Our findings indicate that in advanced coronary disease, increased oxidative stress, reflected by 8-iso-prostaglandin F2α before bypass surgery and enhanced asymmetric dimethylarginine accumulation just after the surgery are associated with cardiovascular death during long-term follow-up

Incretins Enhance PGF2α-Induced Synthesis of IL-6 and Osteoprotegerin in Osteoblasts

Incretins including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted from the small intestine after oral food ingestion, are currently well-known to stimulate insulin secretion from pancreatic β-cells and used for the treatment of type 2 diabetes mellitus. We have previously reported that prostaglandin F2α (PGF2α) stimulates the synthesis of interleukin-6 (IL-6) and osteoprotegerin in osteoblast-like MC3T3-E1 cells, and that IL-6 and osteoprotegerin release are mediated through the p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathways. In the present study, we investigated the effects of incretins including GLP-1 and GIP, on the PGF2α-induced synthesis of IL-6 and osteoprotegerin and examined the detailed mechanism in osteoblast-like MC3T3-E1 cells. We found that GIP and GLP-1 significantly stimulated the PGF2α-induced synthesis of IL-6 in osteoblast-like MC3T3-E1 cells. In addition, GIP and GLP-1 significantly enhanced the PGF2α-induced mRNA expression levels of IL-6. On the other hand, GIP and GLP-1 markedly stimulated the PGF2α-induced synthesis of osteoprotegerin. However, the phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, or JNK induced by PGF2α was not affected by GIP or GLP-1. Therefore, these results strongly suggest that incretins enhance the PGF2α-induced synthesis of IL-6 and osteoprotegerin in osteoblast-like MC3T3-E1 cells. However, these syntheses are not mediated through p44/p42 MAP kinase, p38 MAP kinase, or JNK pathways.

Substance P/NK1R antagonistic effect of 17-Trifluoromethyl phenyl trinor prostaglandin F2α in Breast cancer

17-Trifluoromethyl phenyl trinor prostaglandin F2α (17-TPGF2α) is extracted from Zinc data base, but its value for inhibiting breast cancer through SP/NK1R system remains unknown. This study was designed to investigate the potential antagonist effect of 17-TPGF2α through NK1Receptor. The effect of 17-TPGF2α on the proliferation and apoptosis of breast cancer cell lines were determined through invitro cell lines. Based on invitro results we planned to investigate anticancer activity in Female Balb/c and used SC injection of DMBA for cancer induction. Oral administration of 17-TPGF2α significantly suppress the tumor volume as compared with an untreated group. The serum parameters like ALP, AST and ALT and haematological parameters were normalized in test treated group. Histological examination revealed normal histoarchitecture of mammary gland and focal areas showed minimal inflammatory cell infiltration. There is no necrosis is seen both test treated and standard treated group when compared with Disease group. All these findings concluded that 17-TPGF2α may have potential as a novel antitumor candidate for breast cancer.

Inflammatory Markers in Uterine Lavage Fluids of Pregnant, Non-Pregnant, and Intrauterine Device Implanted Mares on Days 10 and 15 Post Ovulation

Intrauterine devices (IUDs) are used in mares to suppress oestrous behaviour, but the underlying mechanism is yet to be elucidated. The presence of an embryo or an IUD prevents cyclooxygenase-2 (COX-2) and, subsequently, prostaglandin (PG) release and luteolysis. However, inflammation may also be involved. Endometrial inflammatory markers in uterine lavage fluid were measured on Day 10 (EXP 1, n = 25) and Day 15 (EXP 2, n = 27) after ovulation in inseminated mares, non-pregnant or pregnant, and in mares in which a small plastic sphere had been inserted into the uterus 4 (EXP 1) or 3 days (EXP 2) after ovulation. Uterine lavage fluid samples were analysed for nitric oxide (NO), prostaglandin E2 (PGE2) (only Exp. 1), prostaglandin F2α (PGF2α), inhibin A and cytokines, and blood samples for progesterone and oestradiol. On Day 10, the concentration of PGF2α was lower (p < 0.05) in the IUD group than in pregnant mares. The concentration of the modulatory cytokine IL-10 was significantly higher in the IUD group in comparison to non-pregnant mares, and inhibin A was significantly higher in IUD mares than in the pregnant counterparts on Day 15. The results suggest that the presence of IUD causes endometrial inflammation which is at a resolution stage on Day 15.

Inhibition of Prostaglandin F2α Receptors Exaggerates HCl-Induced Lung Inflammation in Mice

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory disorders that are caused by aspiration, sepsis, trauma, and pneumonia. A clinical feature of ALI/ARDS is the acute onset of severe hypoxemia, and the mortality rate, which is estimated at 38–50%, remains high. Although prostaglandins (PGs) are detected in the bronchoalveolar lavage fluid of patients with ALI/ARDS, the role of PGF2α in ALI remains unclear. We aimed to clarify the role of PGF2α/PGF2α receptor (FP) signaling in acid-induced ALI using an FP receptor antagonist, AL8810. Intratracheal injection of hydrochloric acid (HCl) increased neutrophil migration into the lungs, leading to respiratory dysfunction. Pre-administration of AL8810 further increased these features. Moreover, pre-treatment with AL8810 enhanced the HCl-induced expression of pro-inflammatory cytokines and neutrophil migratory factors in the lungs. Administration of HCl decreased the gene expression of lung surfactant proteins, which was further reduced by co-administration of AL8810. Administration of AL8810 also increased lung edema and reduced mRNA expression of epithelial sodium channel in the lungs, indicating that AL8810 reduced fluid clearance. Furthermore, AL8810 also increased lipopolysaccharide-induced expression of adhesion molecules such as intracellular adhesion molecule-1 and E-selectin in human umbilical vein endothelial cells. These results indicate that inhibition of FP receptors by AL8810 exacerbated HCl-induced ALI.

Comparison of efficacy of intramyometrial versus intramuscular prostaglandin F2α (PGF2α) in the management of primary postpartum hemorrhage due to uterine atony.

Objective: To determine the better route of prostaglandin F2α either intramyometrial or intramuscular for the management of uterine atony and to prevent surgical intervention. Study Design: Randomized Controlled Trial. Settings: Bahawal Victoria Hospital. Period: Feb 2018 to July 2018. Material & Method: A total of 266 patients with primary PPH due to uterine atony of 20 to 39 years of age were enrolled in the study. Patients of primary PPH due to bleeding disorders, ruptured uterus, on anticoagulant therapy and hypersensitivity to prostaglandin were excluded. Patients were divided randomly into two groups i.e. Group A (for intramyometrial injection) & Group B (for intramuscular injection). Outcome variables like arrest of bleeding within 30 minutes after start of treatment (efficacy) were noted for successful or unsuccessful outcome. Results: The mean age of women in group A was 26.94 ± 4.43 and in group B was 26.21 ± 4.09 years (p=0.005). The mean parity in group A was 2.92 ± 0.87 and in group B was 2.93 ± 0.98 (p=0.8579). Efficacy was 82.71% in group A (Intramyometrial group) and 91.73% in group B (Intramuscular group) with p-value of 0.0276. Conclusion: This study concluded that intramuscular prostaglandin F2α has better efficacy i.e. 91.73% in a patient of uterine atony for management of primary PPH as compared to intramyometrial rout of administration for prostaglandin F2α.

Estrous synchronization and fertility of cross-bred dairy cows using prostaglandin F2α and gonadotropin releasing hormone

A comparative hormonal study of prostaglandin, gonadotropin releasing hormone and their combination was conducted on 30 randomly selected cross-bred dairy cows of SEMEX project for artificial insemination in Hillat Kuku, Khartoum North, Sudan. The study attempts to determine the response of the animals to hormonal induction and synchronization of estrous as well as fertility following fixed time artificial insemination. Three treatment groups of 10 cows each were undertaken. Groups 1, 2 and 3 involved administration of prostaglandin F2α (PGF2α), gonadotropin releasing hormone (GnRH) and a combination of PGF2α + GnRH, respectively. Descriptive statistical analysis was performed. The results revealed that all the three protocols induced and synchronized estrous were almost synchronous in all the treated groups. However, protocol 3 revealed a significantly (p<0.05) better result of 70% pregnancy rate compared to other two protocols that equally provided 50% pregnancy rates. The study resolves that protocol 3 be highly recommended to change the mindset of farmers about the spread of reproductive technology in Sudan. Protocols 1 and 2 provided acceptable pregnancy rates that can be enhanced with the improvement of management.

PSI-7 Comparison of 6-day versus 7-day CIDR protocol with GnRH and PGFα to synchronize crossbred beef cows for fixed-timed ai with sexed semen at two different times

Preliminary data indicate that shortening the progesterone exposure with CIDR can improve conception rates compared to the established 7-day CO-Synch protocols. The objective was to determine the effects of shortening progesterone exposure from 7 days to 6 days among crossbred beef cows and fixed-time artificial insemination (FTAI) with sex-sorted semen. A total of 147 fall calving (September-November) crossbred beef cows from one location were randomized to one of four treatments: 1 and 4) 7-d CO-Synch + CIDR protocol with administration of gonadotropin-releasing hormone (GnRH) and a CIDR insert on day 0, prostaglandin F2α (PGF) at CIDR removal on day 7, and FTAI occurring 66 h (Treatment 1) or 74 h (Treatment 4) later; 2 and 3) 6-d CO-Synch + CIDR protocol with administration of GnRH and CIDR insert on day 0, prostaglandin F2α (PGF) at CIDR removal on day 6, and FTAI occurring 72 h (Treatment 2) or 80 h (Treatment 3) later. Sex-sorted semen from Angus sires was used for AI. Pregnancy was determined by ultrasound 40 days after AI. Pregnancy rate was analyzed using the MIXED procedure of SAS with CIDR and AI service time as fixed effects. Chi-square analysis was used to assess the number of pregnant and open cows in each treatment using the FREQ procedure of SAS. There was no difference (P = 0.78) in pregnancy rates between 6-d CIDR (0.59 ± 0.05%) and 7 d CIDR (0.57 ± 0.05%) protocols. Cattle bred a shorter period after CIDR removal (0.64 ± 0.05%) had numerically (P = 0.11) greater pregnancy rates compared to those with a longer period after CIDR removal (0.51 ± 0.05%). There was no difference in the number of pregnant and open cows between treatment groups. These data suggest that using a 6-day or 7-day protocol, regardless of breeding time, results in similar conception rates.

PSV-3 Ovarian dynamics of brahman cows submitted to five-day or twelve-day progesterone-based estrus synchronization protocol

The aim of this study was to investigate the ovarian response of Brahman cows submitted to two different estrus synchronization protocols and to determine the estrus response and ovulation time. A total of 153 Brahman cows were randomly assigned to receive one of the following estrus synchronization protocols: 1) CIDR insert and an injection of prostaglandin F2α (25 mg, PGF) on Day -5 and CIDR removal with PGF on Day 0 (CIDR5; n = 77); 2) CIDR insert on Day -12 and an injection of PGF on Day -12, Day -5 and Day 0 upon CIDR removal (CIDR12; n = 76). Estrotect breeding indicator patches were placed on Day 0 and cows were artificially inseminated (AI) 12h after estrus detection; cows not detected in estrus after 96h received TAI coupled with 100 µg of GnRH. Ovarian dynamics were observed during the protocol and follicular diameter were measured every 12h after AI until ovulation. Cows synchronized with CIDR12 had increased follicular diameter (CIDR5, 10.19 ± 0.51 vs. CIDR12, 13.12 ± 0.52 mm; P = 0.01) and decreased serum concentrations of progesterone (CIDR5, 1.68 ± 0.12 vs. CIDR12, 0.81 ± 0.12 ng/ml; P &lt; 0.01) at CIDR removal. The percentage of cows exhibiting estrus did not differ between treatments (CIDR5, 66.2 vs. CIDR12, 64.5%; P = 0.25). No difference was observed in ovulation rate (CIDR5, 94.1 vs. CIDR12, 94.1%; P = 0.6). Time of estrus expression and ovulation time after CIDR removal did not differ (CIDR5, 59.9 ± 2.3 vs. CIDR12, 61.5 ± 2.3h; P = 0.71 and CIDR5, 88.1 ± 2.6 vs. CIDR12, 90.9 ± 2.6h; P = 0.75; respectively). In conclusion, extended length of CIDR with additional PGF increased follicular diameter and decreased concentrations of progesterone but did not influence estrus response and ovulation time in Brahman cows.