Prostaglandin E1 Treatment Research Articles

Effects of Prostaglandin E1 and Balloon Atrial Septostomy on Cerebral Blood Flow and Oxygenation in Newborns Diagnosed with Transposition of the Great Arteries.

Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders followed by alterations in synaptogenesis, gyrification, sulcation, and the microstructure. Brain injuries can occur both pre-operatively and postoperatively, especially white matter injuries, neuronal loss, and stroke. Materials and Methods: In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess the resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure, and 24 h after birth. Cerebral regional saturations of oxygen (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1 + BAS group. Age-matched healthy controls were used for comparison. Results: All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. In addition, 77 newborns composed the control group. PGE1 administration increased crSO2 from 47% to 50% in the PGE1 group, but lower than in controls at 24 h of life, while cFTOE remained elevated. The RI increased 24 h after delivery (0.718 vs. 0.769; p = 0.000002) due to decreased EDV (10.71 vs. 8.74; p < 0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO2 from 42% to 51% at 24 h of life in the PGE1 + BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusions: PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period, as reflected by increasing SpO2 and crSO2.

Hyperbaric Oxygen Therapy and Prostaglandin E on Composite Graft for Fingertip Amputation: Two Case Reports

Fingertip amputation is a common traumatic injury which can be treated with revascularization therapy or composite grafting. This article reports two case studies showing the successful management of fingertip amputation using hyperbaric oxygen therapy (HBOT) and prostaglandin E1 (PGE1) treatment after composite grafting, where revascularization was not possible. HBOT was used to promote angiogenesis, improve oxygen transfer, and accelerate wound healing. At the same time, PGE1 was administered to control inflammation, stimulate cell proliferation, and promote tissue repair. These case reports offer effective approaches to treating fingertip amputation. The treatment strategy used in this study can be expected to improve patient outcomes and quality of life.

Impact of transport outcomes of outborn newborns with critical congenital heart disease on surgery time and mortality rates

Purpose: Transport of neonates with critical congenital heart disease (CCHD) necessitates professional and experienced staff and, well-equipped facilities for both the procedure and post-operative care. In this study, we aimed to evaluate the effect of transport on operation time and survival in neonates with CCHD and determine the relationship between transport characteristics and clinical status.&#x0D; Materials and Methods: A retrospective cross-sectional cohort study was conducted on all infants with CCHD who were transported to a university hospital between January 1, 2019 and December 31, 2019. Transport characteristics such as transport distance, accompanying healthcare provider, vital signs, oxygen saturation levels, prostaglandin E1 (PGE) use, and respiratory support were recorded. The effects of transport characteristics on surgery time, complications, and mortality were analyzed. The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Score was used to analyze mortality-related risks for congenital heart disease. They were compared with inborn newborns with CCHD. &#x0D; Results: A total of 55 patients with CCHD were evaluated. Thirty-one newborns (56.4%) were inborn (Inborn group), and 24 newborns (43.6%) were transferred from another center (Outborn group). There was no difference between the groups in terms of gender, gestational age, birth weight, pre-operative time, and hospital stay. Although the Outborn group had fewer STAT Score categories, there was no difference in the 30-day survival or mortality rates. In the Outborn group, five patients (20.8%) with duct-dependent CCHD were transported without PGE treatment and six duct-dependent (25%) patients received oxygen during transport inappropriately.&#x0D; Conclusion: The administration of PGE and oxygen therapies to specific transported infants was inappropriate. Therefore, referral or transport team members should be familiar infants with CCHD. The impact of transport on surgical timing did not yield a significant effect. However, similar mortality rates were observed in both groups, despite the Outborn group demonstrating lower STAT scores. This may indicate the significance of referring intrauterine transportation to experienced cardiovascular centers.

The effect of multiple doses of misoprostol for missed abortion treatment on subsequent pregnancy outcome

Prostaglandin E1 (PgE1) treatment, known as Misoprostol, is used for 1st trimester missed abortion (MA) treatment, in a single dose or more when products of conception are not entirely expelled. However, an association between the use for multiple doses of Misoprostol and the occurrence of retained products of conception (RPOC) in the subsequent pregnancy, along with other adverse maternal outcome has not yet been evaluated. Our objective was to evaluate the effects of repeated Misoprostol doses on subsequent live pregnancy outcome, especially RPOC.

Cervical histomorphology of successfully detorted uterine torsion affected buffaloes subjected to intracervical hyaluronidase or PgE1 treatment

Twenty-four buffaloes presented between 36-72 h of occurrence of uterine torsion were successfully detorted and equally divided to intracervical hyaluronidase enzyme or prostaglandin E1 (PgE1) treatment or control group for investigating the treatment effectiveness for complete cervical dilatation. Intracervical treatment was administered immediately after detorsion, and cervical biopsy was collected immediately before instituting treatment and at time of cervical dilatation or at 18 h post detorsion in case of non-dilated cervix. The doppler indices of middle uterine artery were evaluated at an hour before detorsion and 0.5 h after detorsion. In control group, none of the buffaloes exhibited cervical dilatation, whereas, 87.5% buffaloes of hyaluronidase group and 62.5% of PgE1 group exhibited cervical dilatation. Following intracervical treatment, lamina propria showed loosely arranged collagen fibres along with hemorrhages, polymorphonuclear (PMN) cells and intercollagen space filled by homogenous/ watery substance in case of dilated cervix. In non-dilated cervix, the collagen fibres were tightly arranged with lesser number of PMN cells and negligible haemorrhages at 18 h after treatment. The doppler indices of the middle uterine artery revealed improvement (P&lt;0.05) in blood supply towards cervix and uterus in buffaloes exhibiting complete cervical dilatation. In conclusion, intracervical hyaluronidase treatment in immediate post-detorsion period in uterine torsion affected buffaloes can be an effective strategy to ensure complete cervical dilatation and per-vaginal fetal delivery.

Prostaglandin E1 attenuates post‑cardiac arrest myocardial dysfunction through inhibition of mitochondria‑mediated cardiomyocyte apoptosis.

Post-cardiac arrest myocardial dysfunction (PAMD) is a leading cause of death in patients undergoing resuscitation patients following cardiac arrest (CA). Although prostaglandin E1 (PGE1) is a clinical drug used to mitigate ischemia injury, its effect on PAMD remains unknown. In the present study, the protective effects of PGE1 on PAMD were evaluated in a rat model of CA and in a hypoxia-reoxygenation (H/R) in vitro model. Rats were randomly assigned to CA, CA+PGE1 or sham groups. Asphyxia for 8 min followed by cardiopulmonary resuscitation were performed in the CA and CA+PGE1 groups. PGE1 was intravenously administered at the onset of return of spontaneous circulation (ROSC). PGE1 treatment significantly increased the ejection fraction and cardiac output within 4 h following ROSC and improved the survival rate, compared with the CA group. Moreover, PGE1 inactivated GSK3β, prevented mitochondrial permeability transition pore (mPTP) opening, while reducing cytochrome c and cleaved caspase-3 expression, as well as cardiomyocyte apoptosis in the rat model. To examine the underlying mechanism, H/R H9c2 cells were treated with PGE1 at the start of reoxygenation. The changes in GSK3β activity, mPTP opening, cytochrome c and cleaved caspase-3 expression, and apoptosis of H9c2 cells were consistent with those noted in vivo. The results indicated that PGE1 attenuated PAMD by inhibiting mitochondria-mediated cardiomyocyte apoptosis.

Prostaglandin E1 effects on CD62p and PAC-1 in patients with sudden sensorineural hearing loss

PerspectivesTo evaluate the treatment outcome of vasodilator prostaglandin E1 (PGE1) in treating sudden sensorineural hearing loss (SSNHL) and to determine its effects on platelet activation, as reflected by changes in CD62p and PAC-1. MethodsWe prospectively enrolled 60 patients with confirmed SSNHL and randomly divided them into two groups: the SSNHL group received regular therapy, and the SSNHL-PGE1 group received additional intravenous injection of PGE1. After 14 days of treatment, we measured clinical improvement and CD62p-positive and PAC-1-positive platelets. 30 healthy medical staff members were included as a control group. ResultsThe SSNHL patients had significantly higher levels of CD62p-positive or PAC-1 positive platelets than the healthy subjects. The ratios of CD62p positive or PAC-1 positive platelets significantly decreased after the two treatments. The average pure tone (PTA) hearing thresholds decreased to 26.51 ± 12.65 dB in SSNHL-PGE1 group after treatment, which was significantly lower than that of the SSNHL group (34.46 ± 10.35 dB). Patients with initial severe or profound hearing loss (PTA ≥ 71 dB) had better hearing improvement on PGE1 than on the regular treatment. Patients in the SSNHL-PGE1 treatment group had significantly lower CD62p and PAC-1 levels than those in the SSNHL group. Patients with higher initial positive CD62p and PAC-1 ratios tended to have higher potential of clinical improvement and hearing gains after PGE1 treatment. Initial CD62p and PAC-1 levels were significantly correlated with hearing thresholds in patients with SSNHL. ConclusionPGE1 application could improve treatment efficacy and suppress excessive platelet activation in patients with SSNHL.

367 Intracavernous Injection of PGE1 and Couple Collaborative Treatment for PDE5i-resistant Psychogenic ED

To explore the therapeutic effects of intracavernous injection of PGE1 (prostaglandin E1) and couple collaborative treatment for PDE5i-resistant Psychogenic ED. Twenty-seven PDE5i-resistant Psychogenic ED patients were treated and observed with a duration of 8 weeks. All patients had no sexual experiences, and were unable to intercourse after receiving at least 4 times of on-demand adequate dose of PDE5i. In all cases, the night tumescence of all patients measured by Rigiscan Plus was physiological, and the arterial flow >30cm/s measured by ICI+CDDU. The matters need attention and procedures of ICI were told by the physician. The wife and sexual partner of twelve patients was educated and explained the inductive of Psychogenic ED, and how to cooperate to fulfill intercourse (Group A). Meanwhile, the wife of rest 15 patients was unwilling to undertake couple collaborative treatment. Patients received ICI of 10 μg of PGE1 15 min before sexual demand, and then fulfilled intercourse. Patients reported their degree of satisfaction of sexual behavior next day and received encouraging psychological suggestion.

Multiparametric MRI Evaluation of Liposomal Prostaglandins E1 Intervention on Hepatic Warm Ischemia-Reperfusion Injury in Rabbits.

Liposomal prostaglandin E1 (Lipo-PGE1) treatment should protect against hepatic warm ischemia-reperfusion injury (WIRI). Improved methods are needed for the noninvasive evaluation of hepatic responses to prophylactic Lipo-PGE1 pretreatment approaches. To demonstrate that multiparametric MRI measurements permit noninvasive differentiation of Lipo-PGE1 treatment outcomes in a hepatic WIRI animal model. Animal study. Seventy rabbits were randomly divided into a sham-operated group (A0), warm ischemia groups experiencing increasing periods of ischemia (A1-A3), and corresponding intervention groups (I1-I3) (n = 10 for each group). Imaging was performed at 3T using a multiecho gradient echo (GRE) sequence (repetition time / echo time [TR/TE], 75/2.57-24.25 msec) for R2* blood oxygenation level-dependent (BOLD) measurements, free-breathing single-shot echo-planar imaging (ss-EPI) sequence with two b-values (0 and 500 s/mm2 ) in 12 diffusion directions for diffusion tensor imaging (DTI), and a free-breathing ss-EPI sequence with eight b-values (0 to 800 s/mm2 ) for intravoxel incoherent motion (IVIM) measurements. The BOLD-derived parameter (R2*), DTI-derived parameters (ADC, FA), and IVIM-derived parameters (Dslow, Dfast, and PF) were calculated for comparisons between treatment groups and correlation to ALT, AST, and LDH levels. One-way analysis of variance (ANOVA), independent sample t-test, Spearman correlation, and receiver operating characteristic (ROC) analysis were performed. Histopathology confirmed the validity of the WIRI model and the efficacy of intervention with clear structure and morphology differences between the different ischemia times and between the Lipo-PGE1 treatment and control groups. Prolonged warm ischemia times resulted in higher R2* and FA values and gradually lower ADC, Dslow, Dfast, and PF values (all P < 0.05). The R2* and FA values were lower, and the ADC, Dslow, Dfast, and PF values were higher in the Lipo-PGE1 intervention groups compared with those in the warm ischemia group for each paired time. However, none of the parameters reached the levels of the A0 group (all P < 0.05). As the warm ischemia time increased, additional parameters demonstrated significant differences between warm ischemia time groups and corresponding intervention groups. At the shortest (30 min), middle (40 min), and longest (60 min) ischemia times, three, four, and five parameters were significantly different between the WIRI and intervention groups, respectively (all P < 0.05). ADC, Dslow, Dfast, and PF values were negatively correlated, while R2* and FA values were positively correlated with serum ALT (|r| = 0.312-0.606) and AST (|r| = 0.432-0.602) (all P < 0.05). ADC and Dfast values showed negative correlations, and R2* showed positive correlations with serum LDH (|r| = 0.323-0.542, all P < 0.05). ROC analysis showed that DTI yielded the strongest diagnostic performance for evaluating the improvement of WIRI. Multiparametric MRI can serve as a noninvasive radiologic evaluation for monitoring the protective impact of Lipo-PGE1 therapy on hepatic WIRI. 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:217-228.

Current therapeutic strategies for erectile function recovery after radical prostatectomy – literature review and meta-analysis

Current therapeutic strategies for erectile function recovery after radical prostatectomy – literature review and meta-analysis

Prostaglandin E1 Alleviates Cognitive Dysfunction in Chronic Cerebral Hypoperfusion Rats by Improving Hemodynamics.

Compensatory vascular mechanisms can restore cerebral blood flow (CBF) but fail to protect against chronic cerebral hypoperfusion (CCH)-mediated neuronal damage and cognitive impairment. Prostaglandin E1 (PGE1) is known as a vasodilator to protect against ischemic injury in animal models, but its protective role in CCH remains unclear. To determine the effect of PGE1 on cerebral hemodynamics and cognitive functions in CCH, bilateral common carotid artery occlusion (BCCAO) was used to mimic CCH in rats, which were subsequently intravenously injected with PGE1 daily for 2 weeks. Magnetic resonance imaging, immunofluorescence staining and Morris water maze (MWM) were used to evaluate CBF, angiogenesis, and cognitive functions, respectively. We found that PGE1 treatment significantly restored CBF by enhancing vertebral artery dilation. In addition, PGE1 treatment increased the number of microvascular endothelial cells and neuronal cells in the hippocampus, and decreased the numbers of astrocyte and apoptotic cells. In the MWM test, we further showed that the escape latency of CCH rats was significantly reduced after PGE1 treatment. Our results suggest that PGE1 ameliorates cognitive dysfunction in CCH rats by enhancing CBF recovery, sustaining angiogenesis, and reducing astrocyte activation and neuronal loss.

Risk factors of mortality and recoarctation after coarctation repair in infancy.

The main challenge of aortic coarctation (CoA) repair in infants is to obtain durable results without morbidity. We aimed to describe predictors of aortic arch reintervention after aortic CoA repair. Between January 2000 and March 2014, we retrospectively included consecutive infants with isolated CoA or CoA with ventricular septal defect (CoA + VSD) who had surgical repair of the aortic arch before 3 months of age. Five hundred and thirty patients were included: 308 (58%) patients had isolated CoA and 222 (42%) patients had CoA + VSD. Three hundred and eighty-five patients (72.6%) had CoA repair, 51 patients (9.6%) had CoA repair with closure of VSD and 94 patients (17.8%) had CoA repair with pulmonary artery banding. Mean age at operation was 13 ± 1.6 days, with 294 patients (55.5%) operated on before 2 weeks. Median follow-up was 7.57 years. Sixty-one patients (11.5%) needed reintervention on the aortic arch. Freedom from aortic arch reintervention was 90% at 1 year and 88.5% at 5 years. Proportions of aortic arch reintervention were similar in the different surgical strategy groups (P = 0.80). However, in patients receiving prostaglandin E1 (PGE1), the end-to-end repair was at higher risk of recoarctation compared to the extended end-to-side repair (P = 0.033). The risk factors of aortic arch reintervention were age at repair <15 days (P = 0.034) and the need for PGE1 infusion at surgery (P = 0.0043). CoA repair in young infants has an overall good outcome. The use of PGE1 may modify the aortic arch anatomy and mask the boundaries of the resection to be performed. PGE1 treatment should be studied more specifically in another study to improve preoperative management.

From compression to injections: Prostaglandins paving a new direction for venous leg ulcer treatment

Objective: Venous ulcers play a major burden on the patient and health-care system in terms of morbidity and medical expenditure. The objective of the study was to evaluate the efficacy of prostaglandin E1 (PGE1) administered via intravenous infusion in the healing time of venous leg ulcer and to evaluate the safety of prostaglandin intravenous infusion. Materials and Methods: This was a prospective observational study at a single tertiary care center. Patients who had proven venous ulcers of the legs which are not healing for more than 3 months with conventional therapy were included. About 500 μg PGE1 was given in equally divided doses over 5 days as intravenous infusion along with regular compression therapy. Ulcers were followed up every 3 weeks for 18 weeks and measurement of ulcer area done. Results: A total of 47 patients with 50 ulcers were included in the study with a mean age of 55.9 years. About 50% of ulcers healed 9 weeks after PGE1 administration and 92% healed after 18 weeks of treatment. The estimated healing time of 25%, 50%, and 75% of the patients treated with PGE1 was 40, 63, and 86 days, respectively, which was statistically significant compared to the previous studies with compression therapy alone. The only factor to independently affect healing time was found to be the initial ulcer size. There were no major adversities with PGE1 administration, 2 patients developed minor symptoms, in the form of hypotension and tachycardia, which were managed with stoppage of infusion for short duration. Conclusion: The study shows the effectiveness of PGE1 in reducing the healing time of VLUs, thereby allowing patients for lesser hospitalization and quicker return to work and life producing improvement in the quality of life. The adverse effects were also very minor with PGE1 treatment, overall, acceptable and were well tolerated by the patients.

Prostaglandin E1 plus methylcobalamin combination therapy versus prostaglandin E1 monotherapy for patients with diabetic peripheral neuropathy: A meta-analysis of randomized controlled trials.

Background:Prostaglandin E1 (P) or methylcobalamin (M) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in many clinical trial reports. However, the combined effects of 2 drugs still remain dubious.Objective:The aim of this report was to evaluate the efficacy of M plus P (M + P) for the treatment of DPN compared with that of P monotherapy, in order to provide a reference resource for rational drug use.Methods:Randomized controlled trials (RCTs) of M + P for DPN published up to September 2017 were searched. Risk ratio (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I2 test. Subgroup and sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects.Results:Sixteen RCTs with 1136 participants were included. Clinical efficacy of M + P combination therapy was significantly better than P monotherapy (fifteen trials; RR 1.25, 95% CI 1.18–1.32, P < .00001, I2 = 27%). Compared with P monotherapy, the pooled effects of M + P combination therapy on nerve conduction velocity were (MD 6.29, 95% CI 4.63–7.94, P < .00001, I2 = 90%) for median MNCV, (MD 5.68, 95% CI 3.53–7.83, P < .00001, I2 = 94%) for median SNCV, (MD 5.36, 95% CI 3.86–6.87, P < .00001, I2 = 92%) for peroneal MNCV, (MD 4.62, 95% CI 3.48–5.75, P < .00001, I2 = 86%) for peroneal SNCV. There were no serious adverse events associated with drug intervention.Conclusions:M + P combination therapy was superior to P monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients. Moreover, no serious adverse events occur in combination therapy.

Effects of Prostaglandin E1 on Patients Undergoing Major Gastrointestinal Surgery.

The aim of this study was to investigate the clinical effects of prostaglandin E1 (PGE1) in patients who underwent surgery for gastrointestinal (GI) trauma, perforation, or obstruction. PGE1 is thought to enhance intestinal blood supply and reduce GI complications during the postoperative period. The medical records of 889 patients undergoing major GI surgery were reviewed retrospectively. Propensity score matching was performed to adjust for any baseline differences. Clinical outcomes, including early GI function recovery, postoperative complications, and length of hospital stay, were evaluated in all patients. In 278 paired patients, selected nutritional, immunologic, and inflammatory variables were compared based on PGE1 administration. After propensity score 1:1 matching, the baseline characteristics were similar for both groups. PGE1 was associated with prompt postoperative GI function recovery, including first bowel movement [2.6 ± 0.9 vs 3.1 ± 1.0 days after surgery in patients with and without PGE1 treatment, risk ratio 0.51, 95% confidence interval (CI) 0.41-0.65, P < 0.001] and first feeding within postoperative day 3 [179 (64.39%) vs 152 (54.68%); risk ratio 0.61, 95% CI 0.42-0.90, P = 0.012]. A lower overall postoperative complication rate, including infectious complications [45 (16.2%) vs 68 (24.5%); odds ratio 0.60, 95% CI 0.39-0.91, P = 0.010] and major complications [23 (8.3%) vs 48 (17.3%); odds ratio 0.43, 95% CI 0.26-0.73, P = 0.001], was noted in patients with PGE1 treatment than in patients without PGE1 treatment. Furthermore, the immunologic and inflammatory variable C-reactive protein on postoperative day 3 was reduced by PGE1 treatment (52.5 ± 36.4 vs 89.6 ± 42.4 mg/L; P = 0.037, t test). PGE1 is associated with beneficial clinical effects, such as prompt postoperative GI function recovery and reduced overall postoperative complications after emergency GI surgery, which may be attributed to a reduced inflammatory response.

Prostaglandin E1 Attenuates Pulmonary Artery Remodeling by Activating Phosphorylation of CREB and the PTEN Signaling Pathway

The depletion of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and phosphatase and tensin homolog (PTEN) is the critical mediator of pulmonary arterial hypertension (PAH). We hypothesized that the activation of phosphorylated CREB (pCREB) and PTEN could inhibit the AKT signaling pathway to attenuate pulmonary arterial remodeling in rats with monocrotaline-induced PAH. We observed decreased PTEN and pCREB in idiopathic PAH versus control tissue. We reduced PTEN using small interfering RNA in human control pulmonary arterial smooth muscle cells (PASMCs) and observed an increase in pAKT. Consistent with PTEN knockdown in PASMCs, prostaglandin E1 (PGE1) induced pCREB expression to stimulate PTEN protein expression and inhibited pAKT in a time- and dose-dependent manner. The enhanced proliferation and migration of PASMCs following PTEN knockdown were significantly inhibited by PGE1 treatment. The PGE1-induced elevation of PTEN expression in PTEN-depleted PASMCs was decreased by the application of a PKA inhibitor and a CBP-CREB interaction inhibitor. Supplementation with a novel emulsion composition comprising PGE1 in rats with monocrotaline-induced PAH prevented pulmonary arterial remodeling and improved hemodynamics via the induced expression of PTEN. We conclude that PGE1 recruits pCREB/PTEN to decrease the migration and proliferation of PASMCs associated with PAH. This finding elucidates a relevant underlying mechanism of the PGE1/CREB/PTEN signaling pathway to prevent progressive PAH.

Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1

Effective treatment of chronic myelogenous leukemia (CML) largely depends on the eradication of CML leukemic stem cells (LSCs). We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal. Using a connectivity map, we identified prostaglandin E1 (PGE1) as a small molecule that partly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency. Although it has little impact on normal hematopoiesis, we found that PGE1 treatment impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft model of transplanted CML patient CD34+ stem/progenitor cells. Mechanistically, PGE1 acted on the EP4 receptor and repressed Fosb andFos AP-1 factors in a β-catenin-independent manner. Misoprostol, an FDA-approved EP4 agonist, conferred similar protection against CML. These findings suggest that activation of this PGE1-EP4 pathway specifically targets CML LSCs and that the combination of PGE1/misoprostol with conventional tyrosine-kinase inhibitors could provide effective therapy for CML.

Long-term results of percutaneous balloon valvuloplasty in neonatal critical pulmonary valve stenosis: a 20-year, single-centre experience.

We carried out a retrospective study of all consecutive newborns with critical pulmonary valve stenosis subjected to percutaneous balloon valvuloplasty at a single centre, between 1994 and 2014, to assess its immediate and long-term safety and efficacy. A total of 24 neonates presented with critical pulmonary valve stenosis. The mean diameter of the pulmonary annulus was 7 mm (±1.19); 33.3% had a dysplastic pulmonary valve, and 92% were started on prostaglandin E1 treatment. Percutaneous balloon valvuloplasty was performed at a mean age of 4.0±4.3 days using, on average, a balloon-to-pulmonary annulus ratio of 1.18 mm (with a range from 0.9 to 1.43). Immediate success was achieved in 22/24 patients (92%) with a reduction in the pulmonary transvalvular peak gradient (p<0.05) and in the right ventricle/systemic pressure ratio (p<0.05). There was one death (4%) 6 days after the procedure, and 29.2% of them had transient rhythm complications. For a mean follow-up time of 8.4 years, the re-intervention rate was 42.9%. In total, 14 re-interventions were performed in nine neonates, including surgery in six. Freedom from re-intervention was 50% at 8 years and 43% at 10 and 15 years. This series, to the best of our knowledge, has had the longest follow-up of neonates with critical pulmonary valve stenosis. Percutaneous balloon valvuloplasty is a safe and effective treatment, and in our study 75% of the patients were exclusively treated using this technique.

PGE1 improves diabetic peripheral neuropathy in patients with type 2 diabetes

BackgroundDiabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes. We aim to investigate the efficacy of Prostaglandin E1 (PGE1) treatment in addition to intensive insulin therapy on DPN in patients with type 2 diabetes. MethodsSeventy-seven patients with DPN received daily intravenous injection of Prostaglandin E1 (PGE1) in lipid microspheres (Lipo-PGE1) for 10days as an additional therapy to standard glucose control therapy (PGE1 group). Another 42 patients with DPN receiving only standard glucose control therapy (intensive insulin therapy) acted as a control group. Michigan neuropathy screening instrument (MNSI) score, neurophysiology examination, transcutaneous oxygen sensory threshold, and ankle-brachial index (ABI) were measured to evaluate the efficacy of PGE1 treatment as compared with control group. ResultsStandard glucose control therapy decreased plasma glucose to a similar level in both PGE1 and control groups. Compare to control group, PGE1 group displayed improvement in several nerve electrophysiological indexes. MNSI score was significantly improved in patients who received PGE1 treatment compared with the control group (p<0.001) after 10days of PGE1 treatment. Similarly, nerve conduction velocity and foot sensory thresholds (p<0.05 for all) also significantly improved compared with the control group after 10days of PGE1 treatment. However, only intensive insulin therapy did not improve any neural function. ConclusionsLipo-PGE1 can effectively improve neural function of patients with DPN.

Short Oxygenated Warm Perfusion With Prostaglandin E1 Administration Before Cold Preservation as a Novel Resuscitation Method for Liver Grafts From Donors After Cardiac Death in a Rat In Vivo Model.

We previously demonstrated that short oxygenated warm perfusion (SOWP) prevented warm ischemia-reperfusion injury in rat livers from donors after cardiac death (DCDs) in an ex vivo model. In the present study, we aimed to examine the in vivo effects of SOWP and SOWP with prostaglandin E1 (PGE1) in DCD rat liver transplants. We performed liver transplantation after 6-hour cold preservation using grafts retrieved from DCD rats, divided into nontreatment (NT), SOWP, and SOWP with PGE1 (SOWP + PG) treatment groups. The SOWP grafts were perfused with oxygenated buffer at 37°C for 30 minutes before cold preservation. Prostaglandin E1 was added to the SOWP + PG group perfusate. Eleven liver transplants from each group were performed to evaluate graft function and survival; 5 rats were used for data collection after 1-hour reperfusion, and 6 rats were used for the survival study. As a positive control, the same experiment was performed in a heart-beating donor group. In both the SOWP and SOWP + PG groups, serum liver enzymes, intercellular adhesion molecule 1 levels, and cellular damage were significantly decreased compared with the NT group. In the SOWP + PG group, bile production and energy status were significantly improved compared with the NT group. The 4-week survival was 0% (0/6), 67% (4/6), 83% (5/6), and 100% (6/6) in the NT, SOWP, SOWP + PG, and heart-beating donor group, respectively. Short oxygenated warm perfusion before cold preservation and the addition of PGE1 to SOWP were thus beneficial in an in vivo rat model.