Administration Of Prostaglandin E2 Research Articles

Critical coarctation of the aorta: diagnostic capabilities and methods of surgical treatment of aortic coarctation in newborns

Critical coarctation of the aorta in newborns usually presents with severe narrowing of the cavotricuspid isthmus and space adjacent to the arterial duct, limiting blood flow to the thoracic aorta. Patient survival depends on duct patency. Rapid deterioration and development of multiple organ failure usually result from spontaneous closure of the patent arterial duct. This deterioration is due in part to reduced renal perfusion and results in fluid and acid retention, causing heart failure and metabolic acidosis. This may be alleviated by the administration of intravenous prostaglandin E1, with a temporary improvement in distal aortic blood flow and the overall condition of the patient. Primary repair is associated with a high risk of unfavourable outcomes due to severe systemic outflow obstruction and multiple organ failure. Therefore, as a bridge to subsequent radical surgery, palliative stenting is the preferred method in newborns with critical aortic coarctation in the decompensated state.Received 16 January 2020. Revised 29 March 2020. Accepted 30 March 2020.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributionsConception and design: S.M. Ivantsov, A.V. Voitov, Yu.Yu. KulyabinDrafting the article: K.A. RzaevaCritical revision of the article: I.A. Soynov, A.V. Gorbatykh, Yu.N. Gorbatykh, A.V. Bogachev-ProkophievFinal approval of the version to be published: K.A. Rzaeva, I.A. Soynov, A.V. Gorbatykh, Yu.Yu. Kulyabin, A.V. Voitov, S.M. Ivantsov, Yu.N. Gorbatykh, A.V. Bogachev-Prokophiev

Comparative Efficacy of Histrelin Acetate and hCG for Inducing Ovulation in Brazilian Northeastern Jennies (Equus africanus asinus)

The goal of this study was to compare the efficiency of histrelin acetate (GnRH analog) and human chorionic gonadotropin (hCG) to hasten ovulation in Brazilian Northeastern jennies (Equus africanus asinus). Thirty cycles of ten jennies were randomly assigned in one of the three groups: G0 (control group), saline; G1, 250 μg of histrelin acetate; G2, 2500 IU of hCG. Jennies were evaluated by transrectal palpation and ultrasonography, and had the administration of an ovulation-inducing agent when a follicle measuring between 29 and 32 mm of diameter was diagnosed. Jennies were monitored every 6 hours by transrectal ultrasonography until ovulation. The interval between prostaglandin administration and ovulation was lower (P < .05) in jennies from the G1 (145.2 ± 34.6 hours) and G2 (147.4 ± 27.3 hours) groups compared with the control cycle (220.0 ± 41.8 hours). Both treatments (G1, 41.15 ± 3.5 hours; G2, 37.8 ± 2.5 hours) also reduced (P < .05) the interval that jennies took to ovulate after the administration of the ovulation-inducing agent compared with the control (81.8 ± 28.8 hours). All jennies from G1 and G2 ovulated up to 48 hours after ovulation induction, whereas 100% of jennies in the control cycle ovulated later (>48 hours from the administration of saline). In conclusion, both histrelin acetate and hCG at the used dose are efficient ovulation-inducing agents in jennies promoting ovulation up to 48 hours after administration.

Cyclooxygenase-2 dependent prostaglandin E2 signaling through the EP3 receptor is required for cell-mediated immunity to Listeria monocytogenes

Abstract The bacterial pathogen Listeria monocytogenes (Lm) is being developed as a cancer immunotherapeutic platform due to its ability to elicit robust CD8+ T cell responses. Though the role of cytokines in Lm-stimulated immunity is well studied, the role of eicosanoids, lipid modulators of inflammation, is unclear. We previously demonstrated that cyclooxygenase-2 (COX-2) dependent prostaglandin E2 (PGE2) is essential for optimal T-cell priming. Antigen specific T cells and protective immunity were decreased following either treatment with the COX-2 inhibitor celecoxib or immunization of mice deficient in microsomal PGE2 synthase-1. Analysis of splenic eicosanoid levels revealed an upregulation of PGE2 twelve hours post immunization and administration of exogenous PGE2 at this time restored immunity during COX-2 inhibition. To understand how PGE2 impacts T-cell priming we assessed the role of the receptors EP1–4 in mediating this response using small molecule agonists and antagonists. EP3 blockade impaired immune responses while the use of an EP3 specific agonist restored immunity during COX-2 inhibition, suggesting that PGE2 signaling through EP3 is critical for T-cell priming. Conversely, consistent with its predicted inverse role in cAMP signaling, EP4 blockade enhanced responses, providing a mechanism by which to improve Listeria-based immunotherapeutics. Ongoing studies with floxed COX-2, EP3 and EP4 mice will illuminate the cell types producing and responding to PGE2. In conclusion, PGE2 signaling through EP3 is necessary Lm-stimulated immunity while EP4 signaling is detrimental. Further understanding these signaling pathways and where they function will be key to optimizing Lm as therapeutic platform.

FERTILITAS KERBAU LUMPUR MENGGUNAKAN INSEMINASI BUATAN DAN KAWIN ALAM PASCA SINKRONISASI BIRAHI

This study was conducted to evaluate the fertility of swamp buffalo synchronized by prostaglandin administration prior to both natural mating and artificial inse-mination (AI). Thirty six swamp buffalo cows were intramuscularly injected by 35 mg prostaglandin (Lutalyse ® , Pfizer, Puurs, Belgium) twice in eleven consecutive days. The buffaloes that exhibit estrous signs allotted into 2 treatments i.e. T1 (natural mating) and T2 (AI). Next to second prostaglandin injection, T1 cows were caged together with bull at 72 h for 2 d, and T2 cows were artificially inseminated at 72 h and 96 h. All cows were observed for next estrous emergence determining non return status. Pregnancy was examined 60 days after insemination by recto-vaginal palpation. The variables measured were non return rate (NRR) and concep-tion rate (CR), analyzed statistically using chi-square test. The results showed that NRR and CR of T1 and T2 had no significant difference. The NRR of T1 and T2 were 88.9% and 83.3% respectively, CR were 72.2% (T1) and 55.6% (T2). In conclusion, natural mating and AI give equal fertility to estrous synchronized swamp buffalo.

Sex-Specific Differences in Neonatal Morbidity at Term [34O

INTRODUCTION: Male sex is associated with worse outcomes among preterm neonates, but it is unclear if such sex discordant morbidity occurs in term infants. The aim of this study was to investigate the relationship between fetal sex and neonatal morbidity at term gestation. METHODS: This is a secondary analysis of a prospective cohort of women admitted for labor at term within a single institution from 2010 to 2015. The primary outcome was composite neonatal morbidity that included death, respiratory distress, mechanical ventilation, meconium aspiration syndrome, suspected sepsis, hypoxic-ischemic encephalopathy, therapeutic hypothermia, and seizure. Multivariable logistic regression was used to estimate the association between infant sex and neonatal morbidity. RESULTS: Of the 8578 participants, 51% delivered a male fetus. Birthweight was higher in male infants (3304 g vs 3177 g, P&lt;.01), as were the rates of prostaglandin administration (19.0 vs 11%, P&lt;.01), operative vaginal (4.0 vs 5.6%, P&lt;.01), and cesarean delivery (15.4 vs 18.6%, P&lt;.01). After adjusting for birthweight, male infants had a significantly higher risk of composite neonatal morbidity (aOR 1.21 [95% CI 1.04, 1.40]). This association was driven primarily by a higher rate of respiratory distress in male infants (1.34 [1.07, 1.68]). CONCLUSION: Term male infants appear to be at increased risk for neonatal morbidity compared to females even after adjustment for birthweight. This association was partly driven by a higher rate of respiratory morbidity in male infants. Our findings reinforce the current notion that neonatal outcomes can be sex-dependent, and call for further investigation into the physiologic mechanisms driving this association.

Effect of Long-term Administration of Prostaglandin E1 on Morphologic Changes in Ductus Arteriosus

To improve survival of patients with hypoplastic left heart syndrome, combination therapy with bilateral pulmonary artery banding and prostaglandin E1 (PGE1)-mediated ductal patency was developed as an alternative for high-risk neonates in Japan. However, the effect of long-term PGE1 administration on ductus arteriosus remains unclear. Synchrotron radiation-based X-ray phase-contrast tomography (XPCT) enables clear visualization of soft tissues at an approximate spatial resolution of 12.5 μm. We aimed to investigate morphologic changes in ductus arteriosus after long-term PGE1 infusion using XPCT. Seventeen ductus arteriosus tissue samples from patients with hypoplastic left heart syndrome were obtained during the Norwood procedure. The median duration of lipo-prostaglandin E1 (lipo-PGE1) administration was 48 days (range, 3 to 123). Structural analysis of ductus arteriosus was performed and compared with conventional histologic analysis. The XPCT was successfully applied to quantitative measurements of ductal media. Significant correlation was found between the duration of lipo-PGE1 infusion and mass density of ductal media (R= 0.723, P= .001). The duration of lipo-PGE1 administration was positively correlated with elastic fiber staining (R= 0.799, P < .001) and negatively correlated with smooth muscle formation (R=-0.83, P < .001). No significant increase in intimal cushion formation was found after long-term lipo-PGE1 administration. Expression of ductus arteriosus dominant PGE2-receptor EP4 almost disappeared in specimens when lipo-PGE1 was administered over 3 days. Disorganized elastogenesis and little intimal cushion formation after long-term lipo-PGE1 administration suggest that ductus arteriosus remodeled to the elastic artery phenotype. Because EP4 was downregulated and ductus arteriosus exhibited elastic characteristics, the dosage of lipo-PGE1 might be decreased after a definite administration period.

Effect of prostaglandins and beta blockers on progression of hypertensive and normotensive glaucomas.

The aim of the study was to evaluate the progression of changes in the visual fields in patients with hypertensive glaucoma (HTG) and normotensive glaucoma (NTG) following administration of prostaglandins and beta blockers, as well as also in NTG without ophthalmological therapy. Methodos. The HTG group included 12 patients (mean age 66 years) with approximately the same changes in the visual field and central corneal thickness (CCT-568um) treated with prostaglandins, and 12 patients (mean age 60 years, CCT=544um) treated with beta-blockers. The IOP ranged from 12 to 18mmHg for the whole follow-up period. The NTG group consisted of three subgroups. The first subgroup consisted of 14 patients (mean age 58 years) who were treated with prostaglandins. The second subgroup consisted of 10 patients (mean age 57 years) who were treated with beta blockers. The third subgroup consisted of 18 patients (mean age 57 years) who underwent no ophthalmological therapy. IOP was within the range of 8-12 mmHg over the whole follow-up period. In all patients, we monitored the pattern defect (PD) and overall defect (OD) within a period of five years. The treatment was not modified during the treatment period. All patients were compensated for cardiovascular status and had no other internal or neurological disease. Visual acuity was 1.0 with a possible correction (less than 3 dioptres) in all patients. There was no statistically significant difference in HTG during the treatment with prostaglandins in PD (P=0.35) and OD (P=0.09) or beta blockers (P=0.37 and 0.23, respectively). In NTG, the greatest changes occurred in PD (P=0.0001) in untreated patients. OD showed no statistically significant changes (P=0.25). Similarly, the patients on prostaglandins had a statistically significant difference in PD (P=0.04), while OD did not show statistically significant changes (P=0.4). We did not find statistically significant differences in progression in patients with NTG treated with beta blockers PD (P=0.7), OD (P=0.4). Treatment of glaucoma with prostaglandins and beta blockers has a significant importance in HTG. However, beta blockers have a higher protective effect on the visual field. This is not true in NTG, where we demonstrated this effect only following the administration of beta blockers.

Combination of dopamine agonist and prostaglandin administration for pregnancy termination in bitches – a novel approach

ABSTRACT Pregnancy termination is a required procedure in companion animal practice. In healthy bitches with confirmed pregnancy, good results are obtained with the combination of prostaglandin F2 and dopamine agonist, followed by regular sonographic examination until confirmed abortion. The aim of this study was to establish a simple and easily applicable procedure, with different dynamics of application of dinoprost and cabergoline. Dinoprost was administered intramucousally in the vestibule of vagina. Twenty bitches were divided into four equal groups. Group A received dinoprost and cabergoline daily; group B received dinoprost every 48 h and cabergoline daily; group C received dinoprost daily and cabergoline every 48 h, and group D received both cabergoline and dinoprost every 48 h. The treatment lasted until abortion was sonographically confirmed. The pregnancy was successfully terminated in all bitches, and side effects appeared in 90% animals, though they were of strong intensity in only 15% of bitches. Dinoprost administered intramucousally was effective with fewer undesirable, strong, systemic side effects. Drug administration every 48 h also induced abortion, with negligible side effects, but with slightly longer duration of treatment. This combination could be interesting in cases with time-limited owners and in countries where other drugs are unavailable.

Hemorrhagic cystitis in pediatric patients: Case presentation with review of the literature and advised treatment algorithm

Hemorrhagic Cystitis after bone marrow transplantation in pediatric patients has a wide clinical spectrum ranging from microscopic hematuria to a life-threatening bleeding. Herein, we describe an unusual case of a 14-year-old male with severe HC and bladder perforation successfully treated by surgery followed by intravesical prostaglandin administration. We discuss the various modalities to treat Hemorrhagic Cystitis and present a proposed treatment scheme.

Level of sodium chloride (NaCl) and profile of cervical mucus of dairy cattle at various age synchronized by prostaglandine

Objectives of this study were to compare the percentage of Sodium Chloride (NaCl) and cervical mucus profile which includes potential of Hydrogen (pH), abundance of cervical mucus, spinnbarkeit and ferning of dairy cattle at different age during estrus cycle. Thirty Two head of dairy cattle were used as materials which are 2 years old (n = 2), 3 years old (n = 18), 4 years old (n = 8) and 5 years old (n=4). Dairy cattle were estrus synchronized using 50 mg/head of prostaglandin. Data was collected on 48, 72, 78, 84, 90, 120, 144 and 408 hours after prostaglandin administration. The data were analyzed by using non parametric statistic which was Kruskal-Wallis H test. The significant data was tested with Mann-Whitney U test. The result showed that the abundance of cervical mucus was significantly different (P&lt;0.05; χ2 = 0.011) on 84 hours after estrus synchronization. However, level of NaCl, abundance, spinnbarkeit and ferning of cervical mucus was not sigificantly different. In conclusion, the age of dairy cattle did not affected to the condition NaCl percentage, spinnbarkeit, pH and ferning of cervical mucus, but affected to the abundance of cervical mucus on 84 hours after adminitration of prostaglandine.

Efficacy of the additional effect of hyperbaric oxygen therapy in combination of systemic steroid and prostaglandin E1 for idiopathic sudden sensorineural hearing loss.

The efficacies of hyperbaric oxygen therapy (HBO), systemic steroid, prostaglandin E1, or the combination of any two modalities have been reported in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). However, little is known about the combined efficacy of HBO, systemic steroid, and prostaglandin E1 for this disorder. We aimed to investigate the efficacy of HBO combined with systemic steroids and prostaglandin E1 as triple therapy in patients with ISSNHL. We retrospectively evaluated the records of 67 patients with ISSNHL who were treated with systemic steroid and prostaglandin E1, with (n=38) or without (n=29) HBO. The inclusion criteria included a diagnosis of ISSNHL within 14days of symptom onset, age ≥15years, treatment according to the protocol, and clinical follow-up of at least 1month. The patients' hearing levels were evaluated 1month after hearing loss onset. The primary outcome was hearing improvement on pure tone audiometry. We also evaluated the demographic profiles of patients. Patients treated with triple therapy showed significantly greater hearing improvement (p<0.01) than those treated without HBO, despite some differences between the two treatment groups. Multivariate logistic regression analysis revealed a significant positive correlation between pure tone audiometry improvement and hyperbaric oxygen therapy, after adjustment for confounding factors (odds ratio=7.42; 95% and confidence interval=2.37-23.3; p=0.001). HBO with systemic steroid and prostaglandin E1 administration conferred significant therapeutic benefits for ISSNHL. Therefore, routine use of triple therapy is recommended for patients with ISSNHL.

Brief Story on Prostaglandins, Inhibitors of their Synthesis, Hematopoiesis, and Acute Radiation Syndrome.

Prostaglandins and inhibitors of their synthesis (cyclooxygenase (COX) inhibitors, non-steroidal anti-inflammatory drugs) were shown to play a significant role in the regulation of hematopoiesis. Partly due to their hematopoiesis-modulating effects, both prostaglandins and COX inhibitors were reported to act positively in radiation-exposed mammalian organisms at various pre- and post-irradiation therapeutical settings. Experimental efforts were targeted at finding pharmacological procedures leading to optimization of therapeutical outcomes by minimizing undesirable side effects of the treatments. Progress in these efforts was obtained after discovery of selective inhibitors of inducible selective cyclooxygenase-2 (COX-2) inhibitors. Recent studies have been able to suggest the possibility to find combined therapeutical approaches utilizing joint administration of prostaglandins and inhibitors of their synthesis at optimized timing and dosing of the drugs which could be incorporated into the therapy of patients with acute radiation syndrome.

Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway.

Proximal renal tubular damage is a critical process underlying diabetic kidney disease (DKD). Our previous study shows that prostaglandin E1 (PGE1) reduces the apoptosis of renal tubular cells in DKD rats. But its underlying mechanisms remain unclear. In this study we investigated the protective effects of PGE1 in DKD rats and high glucose (HG, 30 mM)-treated HK-2 proximal tubular cells. Four weeks after uninephrectomized streptozotocin-induced diabetic rats were established, the DKD rats were administered PGE1 (10 µg· kg−1· d−1, iv.) for 10 consecutive days. We showed that PGE1 administration did not change blood glucose levels, but alleviated diabetic kidney injury in the DKD rats, evidenced by markedly reduced proteinuria and renal tubular apoptosis. In the in vitro experiments, PGE1 (0.1–100 µM) significantly enhanced HG-reduced HK-2 cell viability. In HG-treated HK-2 cells, PGE1 (10 µM) significantly suppressed the c-Jun N-terminal kinase (JNK) and the mitochondrial apoptosis-related protein expressions such as Bim, Bax, caspase-3 and cleaved caspase-3; similar changes were also observed in the kidney of PGE1-treated DKD rats. By using two pharmacological tools-JNK activator anisomycin (AM) and JNK inhibitor SP600125, we revealed that PGE1 blocked HG-triggered activation of JNK/Bim pathway in HK-2 cells; JNK was an upstream regulator of Bim. In conclusion, our results demonstrate that the nephroprotective effects of PGE1 against apoptosis of proximal renal tubule in DKD rats via suppressing JNK-related Bim signaling pathway.

Is prostaglandin F2α administration at the beginning of a progesterone and estradiol-based treatment for FTAI an effective strategy in Bos taurus heifers?

The objective was to evaluate effects of prostaglandin (PG) F2α administration at the beginning of a progesterone and estradiol-based treatment period on ovarian response and pregnancy rate (P/AI) in Bos taurus beef heifers. Heifers were treated with 500 μg of cloprostenol administered: a) in two half-doses (250 μg) at the time of progesterone device insertion and removal (two-PG), or b) in a single dose at the time of device removal (one-PG). In the two-PG group, administration of PG at device insertion resulted in lesser serum progesterone concentrations during the 7-d treatment period (P < 0.05). Additionally, diameter of the follicle from which ovulation occurred was greater, and ovulation occurred earlier in the two-PG compared with one-PG group (P < 0.05). Fixed-time artificial insemination (FTAI) was performed in 3479 heifers with two times for FTAI (48 compared with 54 h from device removal). There was no effect on P/AI percentage for the PG treatment or the time of FTAI. The FTAI at 54 h resulted in a greater P/AI percentage in the one-PG than two-PG group (70.5%, 253/359 and 63.5%, 254/400, respectively; P < 0.05). There were no differences between PG treatments when FTAI was performed at 48 h after device removal. In conclusion, the administration of PG at the time of intravaginal progesterone device insertion results in lesser progesterone concentrations, and an increased size of the follicle from which ovulation occurs, and the time of ovulation is earlier after device removal. The pregnancy rate was not affected by the PG administration at the time of device insertion.

Enhancement of acid-sensing ion channel activity by prostaglandin E2 in rat dorsal root ganglion neurons

Prostaglandin E2 (PGE2) and proton are typical inflammatory mediators. They play a major role in pain processing and hypersensitivity through activating their cognate receptors expressed in terminals of nociceptive sensory neurons. However, it remains unclear whether there is an interaction between PGE2 receptors and proton-activated acid-sensing ion channels (ASICs). Herein, we show that PGE2 enhanced the functional activity of ASICs in rat dorsal root ganglion (DRG) neurons through EP1 and EP4 receptors. In the present study, PGE2 concentration-dependently increased ASIC currents in DRG neurons. It shifted the proton concentration-response curve upwards, without change in the apparent affinity of proton for ASICs. Moreover, PGE2 enhancement of ASIC currents was partially blocked by EP1 or EP4 receptor antagonist. PGE2 failed to enhance ASIC currents when simultaneous blockade of both EP1 and EP4 receptors. PGE2 enhancement was partially suppressed after inhibition of intracellular PKC or PKA signaling, and completely disappeared after concurrent blockade of both PKC and PKA signaling. PGE2 increased significantly the expression levels of p-PKCε and p-PKA in DRG cells. PGE2 also enhanced proton-evoked action potentials in rat DRG neurons. Finally, peripherally administration of PGE2 dose-dependently exacerbated acid-induced nocifensive behaviors in rats through EP1 and EP4 receptors. Our results indicate that PGE2 enhanced the electrophysiological activity of ASICs in DRG neurons and contributed to acidosis-evoked pain, which revealed a novel peripheral mechanism underlying PGE2 involvement in hyperalgesia by sensitizing ASICs in primary sensory neurons.

Effect of Utilization of Single or Double Prostaglandin Administration Within an Ovsynch Fixed-Time Artificial Insemination Protocol During Summer Season in Dairy Cows

Abstract This study investigated the fertility of dairy cows during summer season after treatment with a single or double PGF2α in a progesterone (P4)-based Ovsynch protocol for fixed-time artificial insemination (FTAI). The data were compared to a treatment effectuated during winter season. Two groups of 60 dairy cows each were randomly assigned on day 60 post-partum to single PGF2α or double PGF2α group. At removal of the P4 treatment the single PGF2α group received a single dose and the double PGF2α group received two doses of PGF2α at 24 hours apart. In each group, 30 cows were treated during the summer (June, July and August) and 30 cows during the winter (December, January and February) season. During summer season a double PGF2α dose did not influence pregnancy rate at FTAI but improved cumulative pregnancy rate 60 days after FTAI (43% vs 69% for single PGF2α and double PGF2α administration, respectively; P&lt;0.05). During winter season the single or double PGF2α administration did not modify PR or cumulative PR. In conclusion, during summer the utilization of a double instead of single PGF2α treatment into a P4-based Ovsynch-FTAI protocol did not increase pregnancy rate at FTAI but improved cumulative pregnancy rate.

Histrelin acetate-induced ovulation in Brazilian Northeastern jennies (Equus asinus) with different follicle diameters

The aim of the present study was to evaluate the efficacy of a GnRH analog for induction of ovulation in Brazilian Northeastern jennies (Equus asinus) with different follicle diameters. Four consecutive estrus of 10 jennies were used in a crossover study; C (Control, n = 10) jennies were evaluated by transrectal palpation and ultrasonography until a spontaneous ovulation and the intervals between the predetermined follicular size (25–28 mm [C1], 29–32 mm [C2] and 33–36 mm [C3] follicle) and ovulation were registered. In treated cycle, jennies had the ovulation induced by 250 μg of Histrelin acetate (Strelin®, Botupharma, Botucatu, Brazil) when respective follicle diameters 25–28 mm (T1), 29–32 mm (T2) and 33–36 mm (T3) were diagnosed. Ovulation was monitored by transrectal palpation and ultrasonography. Different follicle diameters significantly affected (P < 0.05) the interval until ovulation between control and matched treated cycles. Interval between prostaglandin administration and ovulation diagnosis was lower in jennies from T2 group (145.2 ± 34.6 h) compared with the control cycle (220.0 ± 41.8 h) and also with other treated cycles (T1 - 209.8 ± 48.0 h; T3 – 183.3 ± 33.9 h). Histrelin acetate treatment also reduces the interval between detection of predetermined follicular size and ovulation (P < 0.05) in all treated cycles groups compared with matched control group. Higher percentage (P < 0.05) of jennies had success of ovulation induction (36–48 h after Histrelin acetate injection) in all treated cycles in contrast with the matched control group. In addition, in comparison among treated cycle groups, more (P < 0.05) jennies (100%) in T2 ovulated between 36 and 48 h after ovulation induction, compared with T1 and T3, which did not differ (P > 0.05) from each other. Edema scoring and ovulation were not associated events (r = 0.0219). In conclusion, jennies with 29–32 mm follicles satisfactory responded to ovulation induction with Histrelin acetate, which allowed the shortening of interovulatory interval in all groups evaluated.

Prostaglandin E2 promotes nitric oxide synthase 2, platelet-activating factor receptor, and matrix metalloproteinase-2 expression in Escherichia coli-challenged ex vivo endometrial explants via the prostaglandin E2 receptor 4/protein kinase a signaling pathway

Prostaglandin E2 (PGE2) is an inflammatory mediator involved in the pathogenesis of several chronic inflammatory conditions, including endometritis. Previous studies have shown that PGE2 accumulates in Escherichia coli-challenged ex vivo endometrial explants, increasing the expression of pro-inflammatory factors and aggravating tissue damage; these alterations are linked to key enzymes involved in the synthesis of PGE2, including cyclooxygenases-2 (COX-2) and microsomal PGES-1 (mPGES-1). In this study, we aimed to investigate whether administration of PGE2 modulated the activities of nitric oxide synthase 2 (NOS2), platelet-activating factor receptor (PAFR), and matrix metalloproteinase (MMP)-2 in E. coli-challenged ex vivo bovine endometrial explants. Our findings showed that COX-2 and mPGES-1 inhibitors significantly reduced NOS2, PAFR, and MMP-2 expression in the E. coli-challenged ex vivo endometrial explants. In addition, NOS2, PAFR, and MMP-2 expression levels were strongly increased in response to treatment with 15-prostaglandin dehydrogenase inhibitors in the E. coli-challenged ex vivo endometrial explants. However, these stimulatory effects could be blocked by PGE2 receptor 4 (EP4) and protein kinase A (PKA) inhibitors. Overall, these findings show that pathogenic PGE2 upregulated NOS2, PAFR, and MMP-2 expression, which may enhance inflammatory damage via the EP4/PKA signaling pathway in E. coli-challenged ex vivo endometrial explants.

GnRH agonista (Acetato de histrelina) en la múltiple ovulación en yegua

The horses have physiological reproductive particularies, presenting peculiarities in the follicular morphophysiology. The pharmacological manipulation of the estrous cycle in the mare is routinely used, since it presents high variation in the duration of estrus. In order to obtain higher conception rates, semen deposition in the female reproductive system should be performed close to the ovulatory period, with the use of only one inseminating dose. For this reason, drugs such as deslorelin acetate and histrelin acetate are used to induce ovulation, as well as multiple ovulations. The aim was to describe the pharmacological effect of histrelin acetate for multiple ovulations in mare. It was used a mare, Quarter Horse, five years old, located in a breeding center in the city of Nossa Senhora do Socorro-SE. For an oocyte ovulation induction was administred Histrelin acetate in the dose of 100 μg, performing evaluation of the reproductive system and monitoring the degree of endometrial edema, follicular diameter and its response to the inducing drug. Ultrasonographic analyzes were performed to identify follicular diameter, with subsequent administration of prostaglandin (PGF2α) to promote luteolysis of the last cycle. For the second cycle, histrelin acetate (100 μg/BID) was administered during five days. On the sixth day the same drug was administered with the first daily dose of (100 μg) and the second dose (250 μg) to induce multiple ovulations. It was concluded that the animal did not respond to the protocol established, believing it to be due to dose used and the start of administration when the follicles have with superior diameters, not demonstrating the expected pharmacological effect.

Administration of a selective prostaglandin E2 receptor agonist attenuates renal fibrosis in vitro and in vivo

Renal fibrosis plays a pivotal role in the development and progression of chronic kidney disease (CKD), which affects 10% of the adult population. Previously, it has been demonstrated that the cyclooxygenase‐2 (COX‐2)/prostaglandin (PG) system influences the progression of renal injury. PGE2 interacts with four different G‐protein‐coupled PGE2 EP receptors, known as EP1–EP4, and plays a role in several biological functions. Previous studies show that the EP2 receptor is involved in progression of lung fibrosis. In this study, we investigated the effect of an EP2 agonist (butaprost) on renal fibrogenesis on a cellular, renal tissue and organismal level using well‐established in vivo and in vitro models as well as a recently developed human model of renal fibrosis. This model is ideal to study multicellular pathological processes, e.g. fibrosis, directly in human tissue since cellular diversity and organ architecture is maintained in the slices. Butaprost (50 μM) reduced TGF‐β‐induced fibronectin (FN) expression, Smad2/3 phosphorylation and epithelial‐mesenchymal transition in MDCK cells. In addition, treatment with 4 mg/kg butaprost attenuated the development of fibrosis in mice that underwent unilateral ureteral obstruction (UUO) surgery, as illustrated by a significant reduction in the gene and protein expression of α‐smooth muscle actin, FN and collagen 1A1. More importantly, a similar anti‐fibrotic effect of butaprost was observed in human precision‐cut kidney slices exposed to TGF‐β. The mechanism of action of butaprost appeared to be a direct effect on TGF‐β/Smad signaling, which was independent of the cAMP/PKA pathway. In conclusion, this study demonstrates that stimulation of the EP2 receptor effectively mitigates renal fibrogenesis in various fibrosis models. These findings warrant further research into the clinical application of butaprost, or other EP2 agonists, for the inhibition of renal fibrosis.Support or Funding Information Sources of support: This work was kindly supported by Lundbeckfonden, grant number R231‐2016‐2344 as well as the Danish Council for Independent Research, grant number 6110‐00231B, Aarhus University Research Foundation, grant number AUFF‐E‐2015‐FLS‐8‐69 and Hildur and Dagny Jacobsens Foundation grant number 1295716‐1.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.