Lipo-prostaglandin E1 Research Articles

Diabetes Mellitus and Bell's Palsy.

The aim of the present brief review was to discuss Bell's palsy (BP) in diabetes mellitus (DM). The risk of BP is increased in DM. DM subjects with BP are more prone to severe facial nerve degeneration. Further characteristics of BP in DM include: a) infrequent taste impairment; b) more frequent and more marked facial nerve subclinical electrophysiological impairment; c) more frequent BR impairment; d) potentially concurrent distal symmetrical sensorimotor polyneuropathy; e) more frequent alternating BP with recurrent episodes affecting different sides of the face.

Intravenous lipo-prostaglandin E1 administration for patients with acute central retinal artery occlusion

ObjectiveThis study aimed to investigate the anatomical and functional changes in patients with central retinal artery occlusion (CRAO) (n=21) treated with 10 µg/day intravenous liposomal prostaglandin E1 (lipo-PGE1).Methods and analysisWe...

A Comparative Study on the Treatment Effect of Lipo-Prostagladin with Hypertension and Diabetes Mellitus in Sudden Sensorineural Hearing Loss Patients

Background and Objectives Several drugs which can improve blood flow have been used as treatment options for sudden sensorineural hearing loss (SSNHL) based on the theory that improvement of perfusion into the inner ear will help restore hearing. Lipo-prostaglandin E1 (lipo-PGE1) is a well-known vasodilator that increases peripheral blood flow. The purpose of this study was to investigate the effect of lipo-PGE1 on the recovery of the SSNHL patients with hypertension or diabetes.Subjects and Method We retrospectively analyzed 801 patients who were diagnosed with SSNHL from January 2007 to December 2018. All patients were treated with 48 mg of methylprednisolone for 5 days; some patients received lipo-PGE1, depending on the attending physician. They were divided into four groups according to the presence or absence of hypertension and diabetes. Hearing test was performed again one month after treatment and compared with the test results at the time of diagnosis.Results As a result of comparing the hearing thresholds before and after the treatment in each group, there was a significant improvement in hearing thresholds in all groups (p<0.001). However, when comparing the effect of lipo-PGE1 for hearing change, there was a significant difference only in the group without any underlying diseases (p=0.016).Conclusion In this study, we show that lipo-PGE1 was helpful in hearing recovery when used in patients without underlying diseases rather than patients with hypertension or diabetes. Further studies will be needed to determine the therapeutic effects of lipo-PGE1 as an adjuvant treatment in SSNHL patients.

Diabetes-induced auditory complications: are they preventable? a comprehensive review of interventions.

Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels, which, over time, lead to major chronic complications in various organs of the body. A growing body of research suggests that diabetes could also result in degenerative changes in the auditory system. To date, several attempts have been made to prevent and reduce diabetes-induced auditory complications. Such attempts have generally focused on disease modifying as well as other pharmacological treatments involving several herbal and non-herbal agents such as vitamins C and E, rutin, resveratrol, coffee, trigonelline, Dioscorea nipponica, red ginseng, Pterostilbene Bofutsushosan, Daisaikoto, tolrestat, ACE inhibitors (enalapril), Ca antagonists (nimodipine), Lipo-prostaglandin E1, methylprednisolone, dexamethasone, and chlorogenic acid and also other strategies like acupuncture. However, there is no consensus about which are the most effective strategies for preventing and reducing auditory complications in diabetic patients with few side effects and maximum efficacy. This paper provides a comprehensive review of interventions for preventing and treating diabetes-induced auditory complications to help therapists.

Orthopaedic Considerations Following COVID-19: Lessons from the 2003 SARS Outbreak.

» As the novel coronavirus disease 2019 (COVID-19) outbreak continues to grow, with 2.5 million cases and 169,006 deaths as of late April 2020, according to the U.S. Centers for Disease Control and Prevention, orthopaedic surgeons should anticipate the complications of pharmacotherapy, namely osteonecrosis, in the next several years.» The rate of osteonecrosis in patients with severe acute respiratory syndrome (SARS) treated with high-dose corticosteroids is 5% to 58% and occurs mostly in the first year following the initiation of high-dose corticosteroid therapy.» Patients who had a cumulative corticosteroid dose of ≥3,000 mg and were treated for >25 days are at the highest risk.» Screening with serum markers and treating with bisphosphonates, extracorporeal shock wave therapy, hyperbaric oxygen, enoxaparin, and/or lipo-prostaglandin E1 may be effective means to curb the progression to collapse and the consequent need for joint replacement in these relatively young patients.

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.

The role of age in determining the effects of lipo-PGE1 infusion on immediate arterial maximal flow velocity in patients with diabetes undergoing free flap surgery for lower extremity reconstruction: A prospective observational study

Diabetes mellitus may have a negative effect on free flap perfusion in patients undergoing reconstructive surgery. Little is known of the effects of lipo-prostaglandin E1 (lipo-PGE1) on flap blood flow in diabetes. This study investigated the effects of lipo-PGE1 on maximal blood flow velocity of the free flap arterial pedicle in patients with diabetes. This prospective observational study assessed maximal blood flow velocity in the arterial pedicle before and 30 min after infusion of 0.4 μg/h lipo-PGE1 in 40 patients with diabetes who received a free flap for lower extremity reconstruction. Multivariate logistic regression analysis was performed to determine whether age, hemoglobin A1c concentration, duration of diabetes, and flap type were significantly associated with increased maximal blood flow velocity after lipo-PGE1 infusion or not. The maximal blood flow velocity of the free flap did not differ significantly before and 30 min after lipo-PGE1 infusion. Multivariate logistic regression analysis showed that age <65 years was the only independent factor associated with increased maximal blood flow velocity after lipo-PGE1 infusion (odds ratio = 5.344; p = 0.022). Assessments of all patients with diabetes undergoing free flap surgery, when age was not taken into consideration, found that lipo-PGE1 did not significantly increase the maximal blood flow velocity of the free flap arterial pedicle. However, when age was taken into consideration, lipo-PGE1 increased blood flow velocity in patients <65 years old, suggesting that age influences the effect of lipo-PGE1 on the blood flow velocity.

Continuous infusion of lipo-prostaglandin E1 for Takayasu\u2019s arteritis with heart failure in an 11-month-old baby: a case report

BackgroundTakayasu’s arteritis is extremely rare in children aged below 6 years. At the onset of Takayasu’s arteritis in children, symptoms are varied but differ from those in adults. Corticosteroids are the mainstay of treatment for preventing irreversible vascular damage but there is no standard treatment for progressive vascular stenosis.Case presentationA Japanese 11-month-old baby boy presented with Takayasu’s arteritis and heart failure, possibly due to afterload mismatch caused by high blood pressure. Computed tomography was performed and revealed thoracic and abdominal aortic aneurysms. It also revealed severe celiac artery stenosis and bilateral renal artery stenosis. Prednisolone was initiated as first-line therapy. The fever resolved, and C-reactive protein levels returned to normal. Although his general condition improved, deterioration of vascular lesions was evident. Celiac artery occlusion, severe right renal artery stenosis, and new superior mesenteric artery stenosis were observed. We decided to use a continuous infusion of lipo-prostaglandin E1 for prevention of branch stenosis of his abdominal aorta. The progression of vascular stenosis was stopped and our patient’s cardiac function gradually improved.ConclusionsA differential diagnosis of heart failure with high blood pressure should be considered in babies. The progression of vascular stenosis may be suppressed by lipo-prostaglandin E1.

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

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. Thirty-seven patients who underwent free flap reconstruction were analysed. Lipo-PGE1 was administered 10minutes after the vascular anastomosis of the free flap. The maximal blood flow velocity was measured at the free flap pedicle artery before and 30minutes after lipo-PGE1 administration using duplex ultrasonography. The primary outcome was the difference in the maximal blood flow velocity before and 30minutes 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. The maximal blood flow velocity was significantly increased at 30minutes 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 30minutes after lipo-PGE1 administration. No lipo-PGE1-related complications occurred. 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.

A clinical analysis of hepatic veno-occlusive disease after hematopoietic stem cell transplantation

Objective: To analyze the outcome and the prognostic factors of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). Methods: A total of 797 patients receiving HSCT were analyzed retrospectively. The prophylaxis regimen of HVOD in the First Affiliated Hospital of Guangxi Medical University consisted of low molecular weight heparin and lipoprostaglandin E1 (PGE1). Results: Fifty-nine patients (7.4%) developed HVOD at 3-49 days after HSCT (median 12 days). Age younger than 15 years at transplant(HR= 6.47, P<0.001), busulphan conditioning (HR=6.40, P<0.001), thalassemia major (HR=6.35, P<0.001), allogeneic transplantation (HR=7.74, P=0.005) were univariate risk factors for HVOD. Multivariate analyses suggested that thalassemia major and busulphan conditioning were independently correlated with the development of HVOD. Conclusion: Thalassemia major and busulphan conditioning are independent risk factors for HVOD after HSCT.

Lipo-prostaglandin E1 improves renal hypoxia evaluated by BOLD-MRI in patients with diabetic kidney disease

ObjectiveTo evaluate the effect of lipo-PGE1 on renal hypoxia in patients with DKD by BOLD-MRI. Materials and methodsAll patients were divided into DKD group and CKD-without-diabetes group. All patients received intravenous 10 μg lipo-PGE1 once daily for 14 days. BOLD-MRI was performed before and after lipo-PGE1 administration to acquire renal CR2* and MR2* values. ResultsRenal MR2* value in DKD group after lipo-PGE1 treatment were significantly decreased compared with the baseline. However, no significant differences in MR2* values were found in the CKD-without-diabetes group. ConclusionsLipo-PGE1 was shown to improve kidney medullary oxygenation in patients with DKD.

Combined pharmacotherapy for osteonecrosis of the femoral head after severe acute respiratory syndrome and interstitial pneumonia: two and a half to fourteen year follow-up

The purpose of this study was to retrospectively analyze the clinical, functional, and radiological outcomes of combined pharmacotherapy to ONFH after high-dose corticosteroid therapy. From August 2003 to June 2015, five patients (ten hips) of ONFH in ARCO stage I, after SARS and Interstitial pneumonia, were treated by combined pharmacotherapy. Lipo-prostaglandin E1 10μg iv Bid × 28days, enoxaparin 6000iu H QD × 12weeks, alendronate sodium tablet 10mg QD × 1year. The patients were fully weight-bearing following completion of the follow-up. For these five patients (ten hips), Harris score was 100 from the diagnosis to final follow-up time. Radiologic findings show no signs of collapse, necrotic focus was repaired, and ARCO stages were changed from IC into IIB. This combined pharmacotherapy has promising treatment results for delaying or preventing collapse of ONFH in ARCO stage I.

Lipo-PGE1 suppresses collagen production in human dermal fibroblasts via the ERK/Ets-1 signaling pathway.

Dysregulation of collagen production contributes to various pathological processes, including tissue fibrosis as well as impaired wound healing. Lipo-prostaglandin E1 (Lipo-PGE1), a lipid microsphere-incorporated prostaglandin E1, is used as a vasodilator for the treatment of peripheral vascular diseases. Lipo-PGE1 was recently shown to enhance human dermal fibroblast (HDF) migration and in vivo wound healing. No published study has characterized the role of Lipo-PGE1 in collagen regulation in HDFs. Here, we investigated the cellular signaling mechanism by which Lipo-PGE1 regulates collagen in HDFs. Collagen production was evaluated by the Sircol collagen assay, Western blot analysis of type I collagen and real time PCR. Unexpectedly, Lipo-PGE1 decreased mRNA expression of collagen 1A1, 1A2, and 3A1. Lipo-PGE1 markedly inhibited type I collagen and total soluble collagen production. In addition, Lipo-PGE1 inhibited transforming growth factor-β-induced collagen expression via Smad2 phosphorylation. To further investigate whether extracellular signal-regulated kinase (ERK)/Ets-1 signaling, a crucial pathway in collagen regulation, is involved in Lipo-PGE1-inhibited collagen production, cells were pretreated with an ERK-specific inhibitor, PD98059, prior to the addition of Lipo-PGE1. Lipo-PGE1-inhibited collagen mRNA expression and total soluble collagen production were recovered by pretreatment with PD98059. Moreover, Lipo-PGE1 directly induced the phosphorylation of ERK. Furthermore, silencing of Ets-1 recovered Lipo-PGE1-inhibited collagen production and PD98059 blocked Lipo-PGE1-enhanced Ets-1 expression. The present study reveals an important role for Lipo-PGE1 as a negative regulator of collagen gene expression and production via ERK/Ets-1 signaling. These results suggest that Lipo-PGE1 could potentially be a therapeutic target in diseases with deregulated collagen turnover.

Comparative Analysis of the Combined Therapeutic Effects of Lipoprostaglandin E1 on Sudden Idiopathic Sensorineural Hearing Loss.

Background and ObjectivesViral and vascular disorders are considered to be a major cause of idiopathic sudden sensorineural hearing loss (ISSNHL). Lipoprostaglandin E1 (lipo-PGE1) has vasodilating activity and has been used to treat ISSNHL. The purpose of this study was to determine the specific therapeutic effects of lipo-PGE1 and compare them to other treatment modalities for ISSNHL.Subjects and MethodsThe study group had 1,052 patients diagnosed with ISSNHL. All were treated with steroid, carbogen inhalation, stellate ganglion block (SGB), or PGE1. The CP group (steroid, carbogen inhalation, and PGE1 injection; 288 patients) was treated with lipo-PGE1 and carbogen inhalation, the CS group (steroid, carbogen inhalation, and stellate ganglion block; 232 patients) with steroid, carbogen inhalation, and SGB, the C group (steroid and carbogen inhalation; 284 patients) with steroid and carbogen, and the control group (steroid only; 248 patients) with steroid only. Patients in the groups receiving lipo-PGE1 received a continuous infusion of 10 µL lipo-PGE1.ResultsThe overall recovery rate after treatment was 52.2%, and recovery rates by group were 67.7% in the CP group, 54.3% in the CS group, 52.1% in the C group, and 32.2% in the control group. Therefore, the therapeutic results in groups treated with lipo-PGE1 were better than results in other groups. The difference was statistically significant.ConclusionsThe study results suggested that the CP group received effective treatment modalities for ISSNHL. The combined therapy of lipo-PGE1 with carbogen inhalation in patients with ISSNHL was more beneficial than other treatment modalities.

Lipo‑prostaglandin E1 modifies cognitive impairment in rats with vascular cognitive impairment by promoting angiogenesis via the VEGF/VEGFR pathway.

The pathological mechanism of vascular cognitive impairment (VCI) involves ischemic lesions in the hippocampus. Prostaglandin E1 (PGE1) serves roles in the promotion of vascular endothelial growth factor (VEGF) expression, angiogenesis and enhances blood flow to ischemic regions. However, the effect of PGE1 on cognitive function in VCI rats and the underlying mechanism are unknown. In the current study, learning and memory function in VCI rats treated by lipo-PGE1 injection was assessed through Morris Water Maze test. Furthermore, the histological alterations, blood vessel numbers in the hippocampal CA1 region and relative VEGF protein and mRNA expression were researched. The results confirmed that VCI rats treated with lipo-PGE1 presented improved cognitive function, less neuronal cell loss, a greater number of blood vessels in the hippocampal region and higher VEGF protein and mRNA expression. However, the role of lipo-PGE1 in VCI rats can be inhibited by SU5416 (a specific VEGFR2 antagonist). The results indicated that lipo-PGE1 may alleviate cognitive deficits in VCI rats. The underlying mechanism may be associated with angiogenesis promoted by lipo-PGE1, which may involve the VEGF/VEGFR pathway. These findings may have therapeutic implications for cognitive impairment induced by hypoperfusion or chronic ischemic lesions.

Pharmacokinetic Analysis of Continuous Intravenous Infusion of Lipo-Prostaglandin E1 As a Prophylaxis of Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation

Introduction: Prostaglandin E1 (PEG1) has various pharmacological effects such as vasodilation, inhibition of platelet aggregation, inhibition of superoxide anion generation, activation of the fibrinolytic system and inhibition of vascular smooth muscle cell proliferation. Continuous intravenous infusion of PGE1 as a prophylaxis of hepatic veno-occlusive disease (VOD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) have previously been shown to be effective. Further study has been done with continuous intravenous infusion of lipo-prostaglandin E1 (lipo-PGE1) because it can be used in smaller doses to avoid toxicities since it is a form of PGE1 dissolved in the lipid emulsion of soybean oil and thus has greater and long lasting effects. However, it has not been evaluated pharmacokinetically.Methods: We performed a prospective explorative pharmacokinetic study on patients who received continuous intravenous infusion of lipo-PGE1 at a dose of 1mcg/kg/day as a prophylaxis of VOD during HSCT at Seoul National University Children's Hospital. Eligible patients were those at high risk of developing VOD (previous abdominal irradiation, liver function abnormality, busulfan or total body irradiation based conditioning, age under 18 years old) but who cannot use low dose heparin due to low platelet count, bleeding tendency or allergy. Dose of lipo-PGE1 could be increased to 1.5mcg/kg/day if patients showed clinical symptoms of VOD, before the establishment of VOD diagnosis. Lipo-PGE1 level was measured before the start of infusion (B level), between 1 hour and 72 hours after the start of infusion (P1 level), and after neutrophil engraftment (P2 level). Additional samplings were done if the dose of infusion was changed or if the condition of the patient changed significantly. Patients were evaluated for the occurrence and severity of VOD. VOD was diagnosed without limitation of onset time, when patients had 2 or more of the following features: serum total bilirubin of greater than 2 mg/dL, hepatomegaly or right upper quadrant pain of liver origin, or unexplained weight gain of greater than 2% over baseline.Results: Thirty patients were enrolled between January 2015 and May 2016 and all of them were eligible for analysis. Patients underwent HSCT at median age of 12.2 years old for hematologic malignancies, solid tumors, brain tumors, and non-malignant diseases. Donors and stem cell sources were variable. Twenty patients received busulfan-based conditioning and 1 patient received total body irradiation based conditioning. Continuous intravenous infusion of lipo-PGE1 was started at median 1 day before the start of the conditioning regimen and was administered for a median duration of 29 days (range, 23-56 days). Dose of lipo-PGE1 was adjusted to 1.5mcg/kg/day in 2 patients at median 18 days (range, 14-21 days) from start of continuous infusion due to increasing serum total bilirubin or tender hepatomegaly. B level and P1 level were measured in all enrolled patients and P2 level was measured in all 28 of the patients who achieved neutrophil engraftment. The P1 level was 6.60 ± 2.88 (mean ± standard deviation) pg/mL and the clearance was 308.48 ± 233.04 L/h. The P2 level was significantly lower than P1 level at 5.55 ± 2.06 pg/mL (P=0.005) and the clearance was greater at 392.64 ± 302.78 L/h but it was not statistically significant (P=0.109). The coefficient of variability (CV%) of lipo-PGE1 level and clearance were 43.64% and 75.54% respectively at P1 and 37.12% and 77.11% respectively at P2. Between-subject variability of lipo-PGE1 level and clearance (11.18 and 51.65 %) were higher than intra-subject variability (7.19 and 7.40 %). No significant relationship was found between the level or clearance of lipo-PGE1 and occurrence or severity of VOD. VOD developed in 2 patients (6.7%) but both resolved completely with antithrombin-III based treatment at median 38 days from diagnosis. There was no adverse event or death related to lipo-PGE1 prophylaxis and there were no deaths related to VOD.Conclusions: We herein provide the first prospective explorative pharmacokinetic data of continuous infusion of lipo-PGE1 as a prophylaxis of VOD in patients undergoing HSCT. We also suggest that lipo-PGE1 is efficient and safe as a prophylaxis of VOD in patients undergoing HSCT. DisclosuresNo relevant conflicts of interest to declare.

Prognostic factors for profound sudden idiopathic sensorineural hearing loss: a multicenter retrospective study.

The aim of this study was to assess the outcomes of various treatment modalities for profound idiopathic sudden sensorineural hearing loss (ISSNHL) and confirm the prognostic factors. In total, 191 patients were enrolled after a thorough medical chart review of patients diagnosed with unilateral, profound ISSNHL (≥90dB). Epidemiological profiles, therapeutic regimens, and the results of pure tone audiometry tests were recorded for all patients. Final recovery was assessed according to Siegel's criteria and by comparing the final hearing level of the affected ear with that of the unaffected ear. The mean follow-up duration and the final hearing level were 75±54days and 77±24dB, respectively. None of the evaluated prognostic factors were significantly associated with complete recovery (<25dB). However, improved hearing in both ears, the absence of dizziness, the use of lipo-prostaglandin E1 (lipo-PGE1), and the use of plasma volume expanders were independently associated with a final hearing level of up to 45dB (p<0.05). Steroid dose reduction, worse initial hearing, and non-use of lipo-PGE1 increased the possibility of no recovery. Although the efficacy of oral steroid treatment for profound ISSNHL has been questioned, steroid dose reduction was significantly associated with no recovery. Therefore, adequate oral corticosteroid doses should be considered in the absence of contraindications. In addition, the use of lipo-PGE1 and/or a plasma volume expander seems preferable for better recovery, and their use for the management of profound ISSNHL should be considered.

Therapeutic effects of lipo-prostaglandin E1 on angiogenesis and neurogenesis after ischemic stroke in rats

Previous studies have demonstrated that prostaglandin E1 (PGE1) has a neuroprotective effect on cerebral ischemia. However, it remains unknown whether PGE1 promotes angiogenesis and neurogenesis after ischemic stroke. In this study, adult male Sprague-Dawley rats were subjected to permanently distal middle cerebral artery occlusion (MCAO). Rats were treated with lipo-prostaglandin E1(lipo-PGE1, 10 μg/kg/d) or the same volume of 0.9% saline starting 24 hours after MCAO daily for 6 consecutive days. All rats were injected 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg) intraperitoneally every 12 hours for 3 consecutive days before being sacrificed. At 7 and 14 days after MCAO or sham-operation, rats were sacrificed. Post-stroke neurological outcome, infarction volume, angiogenesis and neurogenesis were evaluated. Treatment with lipo-PGE1 significantly increased the vascular density in the peri-infarct areas at 7 and 14 days after MCAO. The lipo-PGE1 treatment significantly enhanced the proliferation and migration of endogenous neural stem cells in the ipsilateral subventricular zone. The neural stem cells associated with blood vessels closely within a neurovascular niche in lipo-PGE1-treated rats after stroke. The lipo-PGE1 treatment also significantly improved the neurological recovery after MCAO. These results indicate that treatment with lipo-PGE1 promotes post-stroke angiogenesis, neurogenesis and their interaction, which would contribute to neurological recovery after cerebral infarction. Our study provides novel experimental evidences for the neuroprotective roles of PGE1 in ischemic stroke.

Clinical efficacy of different doses of lipo-prostaglandin E1 in the treatment of painful diabetic peripheral neuropathy

ObjectiveTo observe the clinical efficacy of different doses of alprostadil (lipo-prostaglandin E1, lipo-PGE1) in the treatment of painful diabetic peripheral neuropathy (DPN). MethodsSixty patients with painful DPN were equally and randomly assigned into three groups. Two groups received different doses of lipo-PGE1 by intravenous drip injection (A group: low-dose lipo-PGE1; B group: high-dose lipo-PGE1) following intravenous bolus injection of mecobalamin (MeCbl, 0.5mg once daily (QD)); the third group received MeCbl alone (C group). All patients received optimized treatment to lower blood glucose, blood pressure, and blood lipids to target levels. The efficacy of lipo-PGE1 in the three groups of patients was observed after 3weeks of treatment. ResultsThe overall response rate was 90% in the B group, significantly higher than that in the A and C groups (80% and 55%, respectively; P<0.05). During the observation period, there was no incidence of serious adverse reactions (e.g., acute heart failure, sudden drop in blood pressure, or malignant arrhythmias) in any of the three groups. ConclusionsHigh-dose lipo-PGE1 has better efficacy than low-dose lipo-PGE1 or MeCbl alone in the treatment of painful DPN.

Effects of lipo-prostaglandin E1 on wound bed microcirculation.

Lipo-prostaglandin E1 (lipo-PGE1) is a well-known potent vasodilator that increases peripheral blood flow. However, the effects of this agent on wound bed microcirculation still remain unclear. The present study aims to improve the experimental model which our group developed to visualise wound bed microcirculation and to evaluate acute stimulation by lipo-PGE1. The superficial stratum of the Wistar rat's ear skin was microsurgically excised preserving the subdermal vascular plexus. The preserved vessels, the wound bed microcirculation, were visualised under an intravital microscope-video-computer system. Animals were divided into three groups, a control group in which animals received vehicle control, a medium-dose group (6 μg/2 ml/kg lipo-PGE1) and a high-dose group (10 μg/2 ml/kg lipo-PGE1). The blood velocity and diameter of individual venules were measured from the recorded microcirculatory images, and the blood flow of the venule in the wound bed was evaluated. A significant increase in the wound bed blood flow was seen 10 minutes after lipo-PGE1 injection (p<0.05). This was approximately fourfold the baseline values. The increase was greatest in the medium-dose group. Extravasation and accumulation of lipo-PGE1 in the wound bed was observed. Lipo-PGE1 effectively increased wound bed microcirculation blood flow at the optimal dose. There is no conflict of interest.