Intravenous prostaglandin E1 (alprostadil) bolus in ductus arteriosus-dependent CHD: valid or absolutely contraindicated?

The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.

Effect of prostaglandin-E1 treatment on pyloric wall thickness in newborns with ductal-dependent critical congenital heart diseases.

BACKGROUND: Prostaglandin E1 (PGE1) is used in the medical treatment of ductal-dependent critical congenital heart disease (CCHD) in neonates. Apnea/bradycardia, hypotension, hypokalemia, and fever are the most important side effects of PGE1. Moreover, gastric outlet obstruction has been reported in a few case reports. A prospective study was conducted to investigate the effect of PGE1 treatment on pyloric wall thickness in newborns with congenital heart diseases. METHODS: A total of 22 newborns with ductal-dependent CCHD having PGE1 infusion longer than a week were included in this study. Ultrasonographic measurements were performed before and one week after the PGE1 infusion to evaluate the pyloric thickness and length. The protocol was registered with ClinicalTrials.govidentifier NCT04496050. RESULTS: A total of 22 neonates with mean gestational age 38 ± 1.8 weeks and birth weight 3105 ± 611 gr were enrolled in the study. The median time of the second ultrasound was seven days. The median cumulative dose of PGE1 given during this period was 108 mcg/kg/min. There was a statistically significant increase in post-treatment pyloric thickness and length compared to pre-treatment measurements (p < 0.001, p < 0.001). None of the patients with increased thickness and pyloric muscle length presented any symptoms. CONCLUSION: PGE1 treatment significantly increased the pyloric thickness and length after at least one-week treatment. PGE1 with its action mechanism is likely to cause gastric outlet obstruction, although not exactly pyloric stenosis on the condition used for a long time.

A randomised controlled trial on roles of prostaglandin E1 nebulization among patients undergoing one lung ventilation.

BACKGROUND: Prostaglandin E1 (PGE1) has been reported to maintain adequate oxygenation among patients under 60% FiO2 one-lung ventilation (OLV). This research aimed to explore whether PGE1 is safe in pulmonary shunt and oxygenation under 40% FiO2 OLV and provide a reference concentration of PGE1. METHODS: Totally 90 esophageal cancer patients treated with thoracotomy were enrolled in this study, randomly divided into three groups (n = 30/group): Group A (60% FiO2 and 0.1 µg/kg PGE1), Group B (40% FiO2 and 0.1 µg/kg PGE1), and Group C (40% FiO2, 0.2 µg/kg PGE1). Primary outcomes were oxygenation and pulmonary shunt during OLV. Secondary outcomes included oxidative stress after OLV. RESULTS: During OLV, patients in Group C and B had lower levels of PaO2, SaO2, SpO2, MAP, and Qs/Qt than those in Group A (P < 0.05). At T2 (OLV 10 min), patients in Group C and B exhibited a lower level of PaO2/FiO2 than those in Group A, without any statistical difference at other time points. The IL-6 levels of patients in different groups were different at T8 (F = 3.431, P = 0.038), with IL-6 in Group C being lower than that in Group B and A. MDA levels among the three groups differed at T5 (F = 4.692, P = 0.012) and T7 (F = 5.906, P = 0.004), with the MDA level of Group C being lower than that of Group B and A at T5, and the MDA level of Group C and B being lower than that of Group A at T7. In terms of TNF-α level, patients in Group C had a lower level than those in Group B and A at T8 (F = 3.598, P = 0.033). Compared with patients who did not use PGE1, patients in Group C had comparable complications and lung infection scores. CONCLUSION: The concentration of FiO2 could be reduced from 60 to 40% to maintain oxygenation. 40% FiO2 + 0.2 µg/kg PGE1 is recommended as a better combination on account of its effects on the inflammatory factors. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR1800018288, 09/09/2018.

Prostaglandin E1 attenuates AngII-induced cardiac hypertrophy via EP3 receptor activation and Netrin-1upregulation.

AIMS: Pathological cardiac hypertrophy induced by activation of the renin-angiotensin-aldosterone system (RAAS) is one of the leading causes of heart failure. However, in current clinical practice, the strategy for targeting the RAAS is not sufficient to reverse hypertrophy. Here, we investigated the effect of prostaglandin E1 (PGE1) on angiotensin II (AngII)-induced cardiac hypertrophy and potential molecular mechanisms underlying the effect. METHODS AND RESULTS: Adult male C57 mice were continuously infused with AngII or saline and treated daily with PGE1 or vehicle for two weeks. Neonatal rat cardiomyocytes were cultured to detect AngII-induced hypertrophic responses. We found that PGE1 ameliorated AngII-induced cardiac hypertrophy both in vivo and in vitro. The RNA sequencing (RNA-seq) and expression pattern analysis results suggest that Netrin-1 (Ntn1) is the specific target gene of PGE1. The protective effect of PGE1 was eliminated after knockdown of Ntn1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the PGE1-mediated signaling pathway changes are associated with the mitogen-activated protein kinase (MAPK) pathway. PGE1 suppressed AngII-induced activation of the MAPK signaling pathway, and such an effect was attenuated by Ntn1 knockdown. Blockade of MAPK signaling rescued the phenotype of cardiomyocytes caused by Ntn1 knockdown, indicating that MAPK signaling may act as the downstream effector of Ntn1. Furthermore, inhibition of the E-prostanoid (EP) 3 receptor, as opposed to the EP1, EP2, or EP4 receptor, in cardiomyocytes reversed the effect of PGE1, and activation of EP3 by sulprostone, a specific agonist, mimicked the effect of PGE1. CONCLUSION: In conclusion, PGE1 ameliorates AngII-induced cardiac hypertrophy through activation of the EP3 receptor and upregulation of Ntn1, which inhibits the downstream MAPK signaling pathway. Thus, targeting EP3, as well as the Ntn1-MAPK axis, may represent a novel approach for treating pathological cardiac hypertrophy.

Lipid microsphere-coated PGE1 improves peritoneal transport and reduces inflammation in peritoneal dialysis: A randomized clinical pilot trial.

OBJECTIVE: To evaluate the effects of lipid microspheres coated with prostaglandin E1 (lipo-PGE1) on peritoneal transport function and inflammation in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: In total, 89 patients were randomly allocated to the lipo-PGE1 and control groups. All the patients received conventional treatment, and those in the lipo-PGE1 group received lipo-PGE1 intravenously for 2 weeks. The levels of ß2-microglobulin (ß2-MG), cystatin C, albumin, urea, creatinine, interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and high-sensitivity C-reactive protein (hs-CRP) were measured before and at 1 and 2 weeks after treatment. RESULTS: In the lipo-PGE1 group, the peritoneal clearance rates of ß2-MG, cystatin C, and albumin were significantly increased comparing with pre-treatment values, and the IL-6 appearance rate (AR) in the peritoneal dialysate and the serum levels of IL-6 and hs-CRP were markedly decreased (p < 0.05). The lipo-PGE1 group had significantly higher peritoneal clearance rates of ß2-MG and cystatin C and lower IL-6 AR in the peritoneal dialysate than the control group (p < 0.05). CONCLUSIONS: Lipid microspheres coated with prostaglandin E1 may increase the peritoneal clearance of moderately sized molecules and macromolecules with insignificant effect on the clearance of small molecules. The reduction in IL-6 level following treatment with lipo-PGE1 may alleviate inflammation.

The Influence of Prostaglandin E1 and Use of Inhibitor Percentage on the Correlation between the Multiplate and VerifyNow in Patients on Dual Antiplatelet Therapy.

Platelet function tests (PFT), such as the Multiple Electrode Analyzer (Multiplate) and VerifyNow, show little concordance in patients using antiplatelet drugs. A major difference between these tests is the use of prostaglandin E1 (PGE1) to inhibit P2Y1-platelet-receptor activation in VerifyNow and is proposed to be of influence in the discrepancy between these tests. We aimed to investigate whether the presence of PGE1 could provide an explanation for the moderate correlation and concordance between Multiplate and VerifyNow by adding PGE1 to the Multiplate ADP assay, also known as the ADP-high sensitivity (ADP-HS) assay. We also aimed to investigate whether the difference in baseline platelet function as measured by the VerifyNow and Multiplate could (partly) explain the moderate correlation between the tests, by plotting ADP assay results against baseline function as measured by the corresponding device, which is expressed as the 'inhibitor percentage.' Fifty-one patients who underwent percutaneous coronary intervention (PCI) received dual antiplatelet therapy and were considered to have a high risk of ischemic or bleeding complications were included. The addition of 20 µl PGE1 in the Multiplate resulted in a significant reduction in Arbitrary Aggregation Units, but did not improve correlation with the VerifyNow. The correlation between VerifyNow and Multiplate inhibitor percentage was moderate. Based on these results, we concluded that neither PGE1 nor the calculation of the inhibitor percentage greatly influenced the correlation between PFTs.

Low-dose prostaglandin E1 is safe and effective for critical congenital heart disease: is it time to revisit the dosing guidelines?

INTRODUCTION: Prostaglandin E1 is used to maintain ductal patency in critical congenital heart disease (CHD). The standard starting dose of prostaglandin E1 is 0.05 µg/kg/minute. Lower doses are frequently used, but the efficacy and safety of a low-dose regimen of prostaglandin E1 has not been established. METHODS: We investigated neonates with critical CHD who were started on prostaglandin E1 at 0.01 µg/kg/minute. We reviewed 154 consecutive patients who were separated into three anatomical groups: obstruction to systemic circulation, obstruction to pulmonary circulation, and inadequate mixing (d-transposition of the great arteries). Treatment failure rates and two commonly reported side effects, respiratory depression and seizure, were studied. RESULTS: A total of 26 patients (17%) required a dose increase in prostaglandin E1. Patients with pulmonary obstruction were more likely to require higher doses than patients with systemic obstruction (15/49, 31% versus 9/88, 10%, p = 0.003). Twenty-eight per cent of patients developed respiratory depression and 8% of patients needed mechanical ventilation. Prematurity (<37 week gestation) was the primary risk factor for respiratory depression. No patient required dose escalation or tracheal intubation while on transport. No patient had a seizure attributed to prostaglandin E1. CONCLUSIONS: Prostaglandin E1 at an initial and maintenance dose of 0.01 µg/kg/minute was sufficient to maintain ductal patency in 83% of our cohort. The incidence of respiratory depression requiring mechanical ventilation was low and was mostly seen in premature infants. Starting low-dose prostaglandin E1 at 0.01 µg/kg/minute is a safe and effective therapy for critical CHD.

DUSP-1 Induced by PGE2 and PGE1 Attenuates IL-1ß-Activated MAPK Signaling, Leading to Suppression of NGF Expression in Human Intervertebral Disc Cells.

The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1ß (IL-1ß). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1ß is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1ß-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1ß-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1ß-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1ß-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression.

Effects of prostaglandin E1 nebulization of ventilated lung under 60%O2 one lung ventilation on patients' oxygenation and oxidative stress: a randomised controlled trial.

BACKGROUND: High FiO2 during one-lung ventilation (OLV) can improve oxygenation, but increase the risk of atelectasis and oxidative stress. The aim of this study was to analyze whether Prostaglandin E1 (PGE1) can improve oxygenation and attenuate oxidative stress during OLV under a lower FiO2. METHOD: Ninety patients selectively undergoing thoracotomy for esophageal cancer were randomly divided into three groups (n = 30/group): Group P (FiO2 = 0.6, inhaling PGE1 0.1 µg/kg), Group L (FiO2 = 0.6) and Group C (FiO2 = 1.0). The primary outcomes were oxygenation and pulmonary shunt during OLV. Secondary outcomes included haemodynamics, respiratory mechanics and oxidative stress in serum. RESULTS: Patients in Group P had significantly higher PaO2 and lower shunt fraction in 30 min of OLV compared with Group L. Compared with Group C, patients in Group P had similar levels of PaO2/FiO2 in 60 min and higher levels of PaO2/FiO2 at 2 h during OLV. The levels of PvO2 and SvO2 in Group P and Group L were significantly lower than Group C. Patients in Group P and Group L had significantly higher levels of superoxide dismutase and lower levels of malondialdehyde than Group C. No significant differences were found in SPO2, ETCO2, PaCO2, Paw, HR and MAP among the three groups. The complications in Group C were significantly higher than another two groups. CONCLUSION: PGE1 can maintain adequate oxygenation in patients with low FiO2 (0.6) during OLV. Reducing FiO2 to 0.6 during OLV can decrease the levels of oxidative stress and complications after OLV. TRIAL REGISTRATION: chictr.org.cn identifier: ChiCTR1800017100.

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

PURPOSE: 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. MATERIALS AND METHODS: 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 14 days of symptom onset, age ≥15 years, treatment according to the protocol, and clinical follow-up of at least 1 month. The patients' hearing levels were evaluated 1 month after hearing loss onset. The primary outcome was hearing improvement on pure tone audiometry. We also evaluated the demographic profiles of patients. RESULTS: 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). CONCLUSION: 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.

Efficacy comparison of titrated oral solution of misoprostol and intravenous oxytocin on labour induction in women with full-term pregnancy.

A double-blind randomised trial was conducted on women with gestational age of 40-42 weeks of pregnancy and Bishop score of more than 5. The first group received oxytocin infusion and the second group received a titrated oral solution of misoprostol. Then, the two groups were compared by the primary outcome (the number of deliveries in the first 24 hours of intervention). The two groups did not have any significant difference in maternal and gestational age at the time of intervention, primary Bishop score, parity and neonatal weight. The number of deliveries in the first 24 hours was greater in the misoprostol group. Duration of onset of intervention to proper contractions was longer in the misoprostol group. However, the number of deliveries between 6-12 hours, 12-18 hours and 18-24 hours after induction was greater in the misoprostol group. The incidence of tachysystole and meconium was greater in the misoprostol group.Impact statementWhat is already known on this subject? Labour induction is widely used where the continuation of pregnancy might be dangerous for the mother or the baby. Of the various methods used for induction, misoprostol which is a prostaglandin E1 analogue has been reviewed more in recent years. Misoprostol has various routes of administration but in most studies only vaginal administration has been evaluated, leaving us with limited data about oral administration.What do the results of this study add? Oral misoprostol is a suitable method for labour induction and can be used as an alternative to oxytocin.What are the implications of these findings for clinical practice and/or further research? Misoprostol is not expensive, has a long shelf life, accessible in underdeveloped countries and rural areas and has several routes of administrations such as oral, sublingual and vaginal. Despite the fact that the oral route of misoprostol has a fast absorption and easier administration, there are relatively few studies assessing the the use of the oral route of misoprostol. Misoprostol is a suitable method for Labour induction and it has the potentials of being used as an alternative for oxytocin, however, the optimum dosages, the preferred route of administration, the maximum dose, the maximum time for administration, and maternal and neonatal safety should be studied more.

Lipo-prostaglandin E1 increases immediate arterial maximal flow velocity of free flap in patients undergoing reconstructive surgery.

BACKGROUND: In free flap surgery, the maintenance of proper blood flow after anastomosis of flap pedicle vessels is important. Lipo-prostaglandin E1 (lipo-PGE1) has been empirically administered to prevent blood flow insufficiency in a free flap reconstruction. We tested our hypothesis that lipo-PGE1 administration increases the arterial inflow of free flap. We also evaluated lipo-PGE1-related haemodynamic changes and complications. METHODS: Thirty-seven patients who underwent free flap reconstruction were analysed. Lipo-PGE1 was administered 10 minutes after the vascular anastomosis of the free flap. The maximal blood flow velocity was measured at the free flap pedicle artery before and 30 minutes after lipo-PGE1 administration using duplex ultrasonography. The primary outcome was the difference in the maximal blood flow velocity before and 30 minutes after lipo-PGE1 administration. The arterial blood pressure, heart rate, cardiac output, stroke volume variation, and pulse pressure variation were measured simultaneously. Lipo-PGE1-related complications such as hypotension, bradycardia, hypothermia, facial flushing, diarrhoea, apnoea, and seizure were also investigated. RESULTS: The maximal blood flow velocity was significantly increased at 30 minutes after lipo-PGE1 administration compared to the level before lipo-PGE1 administration (mean (standard deviation): 26.3 (8.7) cm/s vs 22.5 (8.0) cm/s, P = 0.002). The haemodynamic variables were not significantly different before and 30 minutes after lipo-PGE1 administration. No lipo-PGE1-related complications occurred. CONCLUSIONS: Lipo-PGE1 significantly increases the maximal blood flow velocity without complications in patients undergoing free flap reconstruction and may be an effective and safe method of maintaining adequate blood flow in these cases.

Clinical experience with misoprostol vaginal insert for induction of labor: a prospective clinical observational study.

PURPOSE: To provide real-world evidence using misoprostol vaginal insert (MVI) for induction of labor in nulliparous and parous women at two German Level I Centers in a prospective observational study. METHODS: Between 1 August 2014 and 1 October 2015, eligible pregnant women (≥ 36 + 0 weeks of gestation) requiring labor induction were treated with MVI. Endpoints included time to and mode of delivery rates of tocolysis use, tachysystole, uterine hypertonus or uterine hyperstimulation syndrome and newborn outcomes. RESULTS: Of the 354 women enrolled, 68.9% (244/354) achieved vaginal delivery (nulliparous, 139/232 [59.9%]; parous 105/122 [86.1%]; p < 0.001). Median time from MVI administration to vaginal delivery was 14.0 h (nulliparous, 14.5 h; parous, 11.9 h; p < 0.001). A total of 205/244 (84.0%) and 228/244 (93.4%) women achieved a vaginal delivery within 24 h and 30 h, respectively. The most common indications for cesarean delivery were pathologic cardiotocography (nulliparous, 41/232 [17.4%]; parous, 13/122 [10.7%]; p = 0.081) and arrested labor (dilation or descent; nulliparous, 45/232 [19.4%], parous, 3/122 [2.5%]; p ≤ 0.001). A total of 24.3% of women experienced uterine tachysystole and 9.6% experienced uterine tachysystole with fetal heart rate involvement, neither of which were significantly different for nulliparous and parous women. In total, 42/345 (12.2%) of the neonates had an arterial pH < 7.15 and 12/345 3.5% had a 5-min Apgar score ≤ 7. CONCLUSION: When clinically indicated, MVI was efficient and safe for induction of labor in women with an unfavorable cervix. Women, however, should be counseled regarding the risk of uterine tachysystole prior to labor induction with MVI.

[Immediate results of conservative treatment of patients with unreconstructable critical limb ischaemia and trophic changes]. / Blizhaishie rezul'taty konservativnogo lecheniia 'nerekonstruktabel'nykh' bol'nykh s kriticheskoi ishemiei nizhnikh konechnostei s troficheskimi izmeneniiami.

The purpose of the study was to comparatively assess efficacy of using agents belonging to the group of prostaglandin E1 in comprehensive conservative treatment of patients with unreconstructable critical limb ischaemia and trophic changes by the frequency of major amputation, amputation-free survival, and total mortality by combinations of the WIfI classification during a 6-month follow up period. Our retrospective multicentre study enrolled a total of 109 patients, including 60 men and 49 women, with a mean age of 70±7.3 years. The patients were subdivided into 2 groups. Group 1 patients (n=58) received standard conservative therapy without prostaglandin E1 and group 2 patients (n=51) received similar treatment with the use of prostaglandin E1. The statistical analysis (chi-squared test, Fisher criterion, log-rank test) was carried out with regard to stratification of the patients in the groups by the WIfI component combinations. No statistically significant differences between the groups in the frequency of amputation and total mortality were revealed (p=0.094 and p=0.925, respectively). The use of the WIfI classification system made it possible to single out a cohort of patients (with a WIfI combination of 130) for whom the results of administering prostaglandin E1 statistically significantly differed by the frequency of amputation (p=0.042) and by amputation-free survival (p=0.017). No significant differences by these outcomes were obtained for other combinations analysed. A conclusion was drawn that using prostaglandin E1 in comprehensive conservative treatment decreased the frequency of amputation and increased amputation-free survival in patients presenting with unreconstructable critical limb ischaemia and referred to the category with a combination of 130 according to the WIfI classification.

A comparison between induction of labor with 3 methods of titrated oral misoprostol, constant dose of oral misoprostol and Foley catheter with extra amniotic saline infusion (EASI), in women with unfavorable cervix.

Background: Different methods of cervical ripening and induction of labor have been used in the cases of unfavorable cervix with different levels of success, but no method has been found to be the best option. The purpose of the present study was to find the effects and side effects of three different methods of cervical ripening and induction of labor. These three methods were oral titrated misoprostol, constant dose of oral misoprostol and Foley catheter with extra-amniotic saline infusion. Methods: This clinical trial was performed on women with unfavorable cervix who had been admitted in Akbarabadi Teaching Hospital for induction of labor and had bishop score of less than six; between March 2014- March 2015. The eligible women were assigned into three groups. In titrated oral misoprostol group (n=33), titrated solution of misoprostol, and in oral misoprostol group (n=33), 50µg oral misoprostol every four hours and in Foley catheter group (n=50), Foley catheter with extra-amniotic saline infusion were administered. The main outcome was the number of vaginal deliveries during the first 24 hours. In addition, number of cesarean deliveries and adverse effects were compared between the three groups. The obtained data were analyzed using SPSS 18 software. Data analysis was performed according to the intention to treat principle. Chi-square test, Fisher Exact test, Student ttest, and Mann-Whitney U test, were used for comparing data. P-value≤0.05 was considered statistically significant. Results: The three groups did not have any significant difference according to maternal age, gestational age at the time of admission, gravidity, parity, and primary Bishop Score. There was no significant difference between the three groups for the main outcome, which was vaginal delivery during the first 24 hours (p=0.887). There was no significant difference between the three groups according to hypertonicity, uterine hyperstimulation, meconium passage, non-reassuring fetal heart rate, neonatal Apgar score in minutes one and 5, and mean duration of beginning the intervention up to delivery. However, uterine tachysystole and NICU admission were more in the group to whom the titrated solution of misoprostol was administered (p=0.002 and p=0.037 respectively). The number of cesarean deliveries due to failure to progress was higher in the EASI group. However, EASI group showed the least number of none-reassuring fetal heart rate between the three groups. Meconium passage was more in the titrated misoprostol group, but the difference was not significant. Conclusion: All three methods are appropriate methods for induction of labor in the cases of unfavorable cervix; and choosing each method depends on the expertise of labor staff, accessibility to the medications, cost, and taking care for monitoring the patients and adverse effects.

Efficacy of alprostadil in preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention: A multicenter prospective randomized controlled trial.

BACKGROUND: The role of alprostadil on the prevention of contrast-induced nephropathy (CIN) still remains controversial. The purpose of this study was to examine the effects of short-term alprostadil on the incidence of CIN in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: A total of 480 patients with coronary heart disease undergoing PCI were enrolled in our study and randomly assigned to two groups. The control group (n = 240) was given only hydration therapy and the alprostadil group (n = 240) received intravenous administration of 20 ug/day (diluted with 100 ml normal saline) from 0.5∼1 hr before to 3 days after operation on the basis of hydration. The primary endpoint of the study was the incidence of CIN, which was defined as an increase in SCr concentration ≥ 44.2 umol/l or ≥25% above baseline within 48 hr∼72 hr after exposure of contrast media. RESULTS: The incidence of CIN was significantly lower in the alprostadil group than that in the control group (6.25% vs 11.67%, P = 0.038). Multivariate logistic regression analysis showed that alprostadil was the protective factor of CIN (OR = 0.699, 95% CI 0.542-0.902, P = 0.006). The benefits against CIN were consistent in prespecified high-risk patients with diabetes mellitus (P = 0.003). In addition, we also found that hs-CRP and blood homocysteine values after PCI were significantly lower in the alprostadil group than those in the control group. CONCLUSION: Prophylactic administration of alprostadil may prevent against CIN in coronary heart disease patients undergoing elective PCI, particularly in high-risk patients with diabetes mellitus.

Successful retrieval of a migrated neonatal ductal stent and strategies to reposition the expanded stent in the duct.

A neonatal ductal stent deployed in a straight short conical duct on second postnatal day migrated owing to inadequate ductal constriction. It was successfully retrieved using a larger balloon and redeployed in the duct again. Intravenous indomethacin prevented further stent migration. This is the first report of successful transcatheter retrieval and repositioning of a migrated expanded neonatal ductal stent.

Prostaglandin E1 reduces the keratinocyte toxicity of sorafenib by maintaining signal transducer and activator of transcription 3 (STAT3) activity and enhancing the cAMP response element binding protein (CREB) activity.

Hand-foot skin reaction (HFSR) is a common side effect of multiple tyrosine kinase inhibitors (mTKIs). HFSR can necessitate dose reductions or interruption of therapy owing to its negative effect on the quality of life. Therefore, effective use of mTKIs requires measures to prevent HFSR. We evaluated the effect of prostaglandin E1 (PGE1) on HFSR, because PGE1 is already used to treat bed sores and skin ulcers and has established angiogenic and antiproliferative effects in keratinocytes. We found that the pathogenesis of sorafenib-induced HFSR is characterized by a decrease in levels of a phosphorylated signal transducer and activator of transcription 3 (STAT3). We investigated the effect of PGE1 on the sorafenib-mediated reduction in phosphorylated STAT3 levels in HaCaT human epidermal keratinocytes. In cells treated with sorafenib, phosphorylated STAT3 levels decreased in a concentration-dependent manner, and this effect was blocked in cells treated with sorafenib and PGE1. Furthermore, the expression of phosphorylated STAT3, the antiapoptotic proteins myeloid cell leukemia-1 (Mcl-1) and survivin decreased in cells pretreated with an inhibitor of cAMP response element binding protein (CREB). Cell viability increased in cells treated with sorafenib and PGE1 compared with that in cells treated with sorafenib alone, and these effects were not observed in STAT3 knockdown HaCaT cells. Collectively, these findings indicate that PGE1 blocks the inhibitory effects of sorafenib on cell growth by maintaining the activity of STAT3 and enhancing the CREB activity. Therefore, PGE1 might represent an effective treatment for the prevention of sorafenib-induced HFSR.

The key residue within the second extracellular loop of human EP3 involved in selectively turning down PGE2- and retaining PGE1-mediated signaling in live cells.

Key residues and binding mechanisms of PGE1 and PGE2 on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the ß2-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE1 and PGE2 docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site. While PGE2 could form possible binding contact with S211, PGE1 is unable to form similar contacts. Therefore, S211 could be the critical residue for PGE2 recognition, but is not a significant for PGE1. This prediction was confirmed using HEK293 cells transfected with hEP3 S211L cDNA. The S211L cells lost PGE2 binding and signaling. Interestingly, the S211L cells retained PGE1-mediated signaling. It indicates that S211 within the second extracellular loop is a key residue involved in turning down PGE2 signaling. Our study provided information that S211L within EP3 is the key residue to distinguish PGE1 and PGE2 binding to mediate diverse biological functions at the initial recognition step. The S211L mutant could be used as a model for studying the binding mechanism and signaling pathway specifically mediated by PGE1.