Objective: To investigate the protective role of alprostadil on aortic dissection. Methods: 26 C57BL6 male mice were divided into control group (normal drinking water, n=13) and model group (1 g·kg^-1·d^-1 BAPN via drinking water, n=13). On day 14, mRNA expression of inflammatory-related genes as well as EP receptor families were detected by RT-PCR (n=6 each) and EP4 protein levels were determined by Western blot (n=7 each). Another 88 mice were divided into 3 groups: control group (n=22), model group (n=33) and treatment group (n=33). The mice in model group and treatment group were applied with BAPN (1 g·kg^-1·d^-1) via drinking water. The mice in treatment group received additional intraperitoneal injection with alprostadil (80 μg·kg^-1·d^-1) for 28 days. The mice in the control and model group received equal volume intraperitoneal injection with 0.9% saline respectively. The body weight and systolic blood pressure, the mortality and morbidity were monitored from the beginning until the designed end of the study. On day 28, the mice were sacrificed and aorta were fixed, embedded and sliced, followed by staining with HE and Victoria Blue. The distribution of EP4 was determined by immunohistochemistry in control (n=6) and model group (n=6). Furthermore, the concentration of PGE1 were tested among model (n=3) and treatment group (n=4). EP4 protein expression was determined in model group (n=7) and treatment group (n=6). Results: On day 14, mRNA expression level of MCP-1 ((2.74±1.55) vs. (1.00±0.49),<0.05) and MMP2((1.38±0.42) vs. (1.00±0.27), P<0.05) was significantly upregulated in model group compared with control group. Protein expression of EP4 receptor also increased in aorta in model group compared with control group (1.48±0.51 vs. 1.00±0.19, P<0.05). In the dissection area, the EP4 expression was also enriched compared with non-dissection area, particularly in endothelial cells and inflammatory cells on day 28. BAPN applied in drinking water (model and treatment groups) successfully induced the aortic dissection in mice, some mice died of the rupture. The elastic fibers were fractured, and the infiltrated immune cells were visible in dissected tissue. False lumen was formed. There was no dissection and death in the control group. Compared with control group, the morbidity and mortality rates were significantly increased in the model group (60.6%, 20/33, 30.3%, 10/33) and the treatment group (72.7%, 24/33, 24.2%, 8/33). The mortality and morbidity rates were similar between model and treatment groups. There is no difference in terms of SBP among three groups (P>0.05). Further study showed that after alprostadil injection, the blood concentration of PGE1 was increased in treatment group ((0.540±0.041 vs. 0.436±0.012)μmol/L, P<0.05). Besides, the EP4 receptor expression was downregulated in the treatment group compared to model group (0.60±0.30 vs. 1.00±0.20, P<0.05). Conclusion: EP4 expression is upregulated in BAPN induced aortic dissection mouse model. No protective effects are observed post alprostadil treatment in this model probably due to the reduced expression of EP4.
Alprostadil ; Aminopropionitrile ; Aneurysm, Dissecting ; Animals ; Disease Models, Animal ; Endothelial Cells ; Male ; Mice

OBJECTIVE: To investigate multilineage-differentiating stress-enduring (Muse) by immunomagnetic bead screening from Wharton's jelly mesenchymal stromal cells(WJ-MSCs), and explore transplantation of Muse cell for safety and effectivensess of sub acute cord injury in rats. METHODS: Donated Wharton's Jelly-mesenchymal stromal cells (WJ-MSCs) were successfully derived from a human umbilical cord by a series of procedures namely physical isolation of Wharton's Jelly from cord membrane, collagenase and trypsin treatment and density gradient centrifugation. Magnetic activated cell sorting was performed to specifically select SSEA3+ Muse cells, and flow cytometry and immunocytochemistry were used to identify further. In vivo, spinal cord contusion injury model in rats was induced by NYU-III impactor, and were randomly divided and equally into four groups, namely group A (sham), group B (control), group C (Non-Muse cells transplantation) and group D (Muse cells transplantation). Laminectomy was conducted in group A but no spinal cord contusion injury. Laminectomy and cord injury were performed in group B, C and D, 10 g trip rod was freely falling down from 12.5 mm. Two weeks later, group B, C and D were received PBS injection, Non-Muse cells transplantation and Muse cells transplantation respectively, four-point injection were performed in each cord with totally 4×10⁵ cells. BBB scores were evaluated on 1 day, 1, 2, 3, 4, 5 and 6 week after injury. Four weeks after cell transplantation, the rats were sacrificed, and immunohistochemistry were carried out to observe survival, migration and differentiation of the injected cells. RESULTS: The expression of CD105, CD90 and CD73 were over 99.5% in the derived WJ-MSCs population, but CD45 and CD14 were lower than 0.5%, positive rate of SSEA3+ was 1.46% under flow cytometer, However, after MACS sorting, the percentage of 92.0% Muse cells expressed SSEA3 and CD105, and immunohistochemistry results of SSEA3 showed typically membrane morphology with special processes. In vivo, BBB scores was 21 in group A at different time points. One-way ANOVA and LSD analysis showed that BBB scores in group C and D were significantly higher than that in group B (=0.004, 0.002), but there was no significantly difference between group C and D. Further intra-group paired t test showed that BBB score was significantly higher at 4 weeks than that 3 weeks in group C (=0.005). However, in group D, BBB scores were significantly higher at 4 and 6 week than those at 3 and 5 weeks, values were 0.005 and 0.016 respectively. Immunohistochemistry results showed that both Muse cells and Non-Muse cells could survive for 4 weeks in rats and they migrated from the four-point injection to injury site. But there showed more Muse cells survival than Non-Muse cells in the cord. CONCLUSIONS Immunomagnetic bead screening is efficient to select large number of purified SSEA3+ Muse cells. Muse cells could survive and target-migrate in injured cord to improve BBB scores continuously. Muse cells are a novel kind of seed cells in the spinal cord injury treatment.
Alprostadil ; Animals ; Cell Differentiation ; Cells, Cultured ; Humans ; Mesenchymal Stem Cells ; Rats ; Spinal Cord Injuries ; Umbilical Cord ; Wharton Jelly

PURPOSE: In this study, we aimed to determine the role of extracorporeal shockwave therapy (ESWT) in the management of Peyronie's disease (PD). MATERIALS AND METHODS: A total of 325 patients suffering from PD were enrolled in this single-arm clinical study. All patients were received ESWT using a schedule of 1 treatment/wk. Penile curvature was measured by a goniometer after intracavernosal drug-induced erection using Alprostadil. Plaque size was measured with a ruler and sexual function assessed by the international index of erectile function (IIEF)-15 score. Severity of erectile dysfunction was classified as severe (IIEF-15 ≤10), moderate (IIEF-15 between 11 and 16), or mild (IIEF-15 between 17 and 25). Results were evaluated at baseline and 3 months after the treatment. RESULTS: All the patients completed the study protocol. Median age was 59.0 years (55.0–64.0 years). After treatment, the median (interquartile range, IQR) plaque size reduced from 1.78 cm2 (1.43–2.17 cm2) to 1.53 cm2 (1.31–1.96 cm2) (p<0.001); the median (IQR) penile length in erection increased from 13.0 cm (12.0–14.0 cm) to 14 cm (13.0–15.0 cm) (p<0.001) and the median (IQR) penile curvature from 30.4° (22.2°–35.4°) to 25.0° (20.2°–30.4°) (p<0.001). We also observed a decrease in pain assessed by visual analogue scale (7 vs. 3; p<0.001), an improvement in each of the IIEF sub-domains (p<0.001) and an improvement in all three PD questionnaire domains (p<0.001). CONCLUSIONS: Based on our findings, ESWT could be considered a safe and efficient minimally invasive option for the management of the patients suffering from PD.
Alprostadil ; Appointments and Schedules ; Clinical Study ; Erectile Dysfunction ; Humans ; Male ; Observational Study ; Penile Diseases ; Penile Induration ; Shock ; Treatment Outcome

OBJECTIVETo investigate the protective effect of prostaglandin E1 (PGE-1) against brain injury induced by hyperoxia in neonatal rats and observe the changes in the expression of glucose-regulated protein 78 (GRP78) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and to provide a theoretical basis for the clinical application of PGE-1 in the treatment of neonatal brain injury induced by hyperoxia.

METHODSSixty neonatal Wistar rats were randomly divided into air control group, hyperoxic brain injury model group, and hyperoxic brain injury+PGE-1 group. All rats except those in the air control group were treated to establish a hyperoxic brain injury model. From the first day of modeling, the rats in the hyperoxia brain injury+PGE-1 group were intraperitoneally injected with PGE-1 2 μg/kg daily for 7 consecutive days, while the other two groups were treated with normal saline instead. The water content of brain tissue was measured; the pathological changes of brain tissue were evaluated by hematoxylin-eosin staining; the apoptosis of brain cells was assessed by nuclear staining combined with TUNEL staining; the protein expression of GRP78 and CHOP in brain tissue was measured by Western blot.

RESULTSThe water content of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P<0.05); the water content of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P<0.05). The pathological section of brain tissue showed inflammatory cell infiltration and mild cerebrovascular edema in the brain parenchyma in the hyperoxic brain injury model group; the periparenchymal inflammation and edema in the hyperoxic brain injury+PGE-1 group were milder than those in the hyperoxic brain injury model group. The apoptosis index of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P<0.05); the apoptosis index of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P<0.05). The protein expression of GRP78 and CHOP in brain tissue was significantly higher in the hyperoxic brain injury model group than in the hyperoxic brain injury+PGE-1 group and air control group (P<0.05); the protein expression of GRP78 and CHOP was significantly higher in the hyperoxic brain injury+PGE-1 group than in the air control group (P<0.05).

CONCLUSIONSPGE-1 has a protective effect against hyperoxia-induced brain injury in neonatal rats, which may be related to the inhibition of cell apoptosis by down-regulating the expression of GRP78 and CHOP.

Alprostadil ; therapeutic use ; Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Brain ; pathology ; Brain Injuries ; metabolism ; pathology ; prevention & control ; Heat-Shock Proteins ; analysis ; Hyperoxia ; complications ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Wistar ; Transcription Factor CHOP ; analysis

Replantation using microvascular anastomosis is considered to be the optimal method in treating the amputated ear in terms of resulting color, texture, and shape. Only a few cases of ear replantation have been reported because it is anatomically difficult to identify suitable vessels for anastomosis. We successfully replanted the amputated helical rim of the ear using single arterial anastomosis. A 37-year-old man had his helical rim amputated by a human bite. The amputee was about 4 × 1 cm in dimension, composed of skin and soft tissue including auricular cartilage. Replantation was performed anastomosing a small artery of the amputee with a terminal branch of the posterior auricular artery. After replantation, intravenous heparinization was performed and prostaglandin E1 and aspirin were administered. Venous congestion was decompressed by stab incisions applied with heparin solution soaked gauze. Venous congestion of the amputee slowly began to resolve at 4 days after the operation. The amputated segment of the helical rim survived completely with good aesthetic shape and color. The authors propose that performing microvascular anastomosis should be attempted especially if it is possible to detect vessels on cut surfaces of ear amputee and stump. Proper postoperative care for venous congestion, arterial insufficiency, and infection should be followed for amputee survival.
Adult ; Alprostadil ; Amputation ; Amputees ; Arteries ; Aspirin ; Bites, Human ; Ear ; Ear Cartilage ; Heparin ; Humans ; Hyperemia ; Methods ; Microsurgery ; Postoperative Care ; Replantation* ; Skin

BACKGROUND AND OBJECTIVES: Viral 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 METHODS: The 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. RESULTS: The 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. CONCLUSIONS: The 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.
Alprostadil ; Hearing Loss, Sensorineural* ; Humans ; Inhalation ; Stellate Ganglion ; Therapeutic Uses*

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in pulmonary arterial pressure and excessive thickening and remodeling of distal small pulmonary arteries. During disease progression, PAH include increase in mean pulmonary arterial pressure, right ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting various pathways involved in PAH progression have been approved by the Food and Drug Adminstration. However, many of the currently available anti-PAH drugs suffer from a number of limitations, including short biological half-life, and poor pulmonary selectivity. Prostaglandin E1 (PGE1) is a potent vasodilator with selectivity toward pulmonary circulation when it is administered via the pulmonary route. However, PGE1 has a very short half-life of 5–10 minutes. Therefore, we hypothesized that long-term effect of PGE1 could reduce mal-adaptive structural remodeling of the lung and heart and prevent ventricular arrhythmias in monocrotaline-induced rat model of PAH. Our results revealed that PGE1 reduced ventricular hypertrophy, protein expressions of endothelin-1 and endothelin receptor A, and the expression of fibrosis. These results support the notion that PGE1 can improve the functional properties of RV, highlighting its potential benefits for heart and lung impairment.
Alprostadil* ; Animals ; Arrhythmias, Cardiac ; Arterial Pressure ; Arterioles ; Disease Progression ; Endothelin-1 ; Fibrosis ; Half-Life ; Heart ; Heart Ventricles ; Hypertension* ; Hypertrophy ; Lung ; Models, Animal ; Muscle, Smooth ; Pulmonary Artery ; Pulmonary Circulation ; Rats* ; Receptors, Endothelin ; Vascular Diseases ; Vascular Resistance

OBJECTIVETo investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.

METHODSThe effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without ω-3, ω-6, PGE2 and PGE3 were designed as the control.

RESULTSWith the increased concentration of ω-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by ω-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by ω-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, ω-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, ω-6 could increase angiogenesis of gastric cancer cells(P<0.01), but ω-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, ω-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but ω-6 had no effect on angiogenesis.

CONCLUSIONSThe PUFA ω-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the ω-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.

Alprostadil ; analogs & derivatives ; pharmacology ; Angiogenesis Inducing Agents ; metabolism ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Cell Count ; methods ; Cell Line, Tumor ; drug effects ; physiology ; Cell Migration Assays ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Coculture Techniques ; Cyclooxygenase 2 ; pharmacology ; Dinoprostone ; metabolism ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; metabolism ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; physiology ; Humans ; Lactones ; pharmacology ; Neovascularization, Pathologic ; physiopathology ; Stomach Neoplasms ; physiopathology ; Sulfones ; pharmacology

PURPOSE: In patients with erectile dysfunction, it is important to differentiate psychogenic from organic causes. Penile Doppler ultrasonography is a relatively inexpensive and minimally invasive tool for this purpose. This study was conducted to evaluate the causes of erectile dysfunction in an adult male population, using penile Doppler ultrasonography. MATERIALS AND METHODS: A retrospective study was conducted in a single center. All patients who presented with complaints of erectile dysfunction and underwent penile Doppler ultrasonography between July 2014 and June 2016 were included in this study. All examinations were performed using GE Voluson S6 and GE Logiq P5 devices. Following baseline scans, an intracavernosal injection of 20 µg of prostaglandin E1 was given. Peak systolic and end diastolic velocities were measured in each cavernosal artery. Patients with a peak systolic velocity of <25 cm/s were considered to have arterial insufficiency, while an end diastolic velocity of >5 cm/s was considered to indicate venous incompetence. RESULTS: Out of 97 patients (mean age, 37.09±11.59 years; range, 19~69 years), 50 patients (51.5%) had normal findings, 24 patients (24.7%) had arterial insufficiency, 15 patients (15.5%) had a venous leak, and 8 patients (8.2%) patients had arterial insufficiency with a venous leak. Psychogenic erectile dysfunction was significantly higher among patients aged ≤40 years, while arterial insufficiency with or without a venous leak was significantly higher among patients aged >40 years (p=0.022). CONCLUSIONS: A majority of the studied individuals demonstrated no organic cause of erectile dysfunction, thus confirming a high prevalence of the psychogenic etiology, particularly in relatively young individuals.
Adult ; Alprostadil ; Arteries ; Erectile Dysfunction* ; Female ; Humans ; Impotence, Vasculogenic ; Male ; Pakistan* ; Prevalence ; Retrospective Studies ; Ultrasonography ; Ultrasonography, Doppler*

BACKGROUND: Pre-induction of labor cervical ripening increases success of labor induction when there is unfavorable cervix. Evening primrose oil soft gel capsule contains linoleic and gamma-linolenic acid, which are precursors of prostaglandins E1 andE2.
OBJECTIVE: To measure the effectiveness of evening primrose oil capsule as a cervical ripening agent by measuring the Bishop score before and 4 hours after intravaginal insertion of six capsules.
METHODS: A quasi-experimental cross-sectional study was conducted from the period of May to July 2016 involving labor induction patients with a Bishop score ?4, an intact amniotic sac and a Biophysical profile score of 10/10 or 8/8.
RESULTS: Thirteen patients had an average age of 27±6 years, and a mean age of gestation of 40±1 weeks. Seven patients (54%) were nulliparous, 2 (15%) were primiparous and 4 (31%) were multiparous. Seven patients (54%) had hypertension, 1 (8%) had diabetes mellitus, 5 (38%) had post-term pregnancies. A paired t-test was done to check for statistically significant changes in the Bishop score. Change in the Bishop score from baseline to 4 hours after insertion of evening primrose oil capsules was statistically significant (p=0.001). Eleven patients (85%) had improvement in the Bishop score after 4 hours, 4 (31%) of which had a clinically significant change in the Bishop score (?4). Specifically, there were statistically significant changes in the dilatation (p=0.027), effacement (p=0.006) and consistency (p=0.002). The mean birth weight of deliveries was 3192±351 grams. Nine patients (69%) underwent primary low segment cesarean section, six (46%) of which for nonreassuring fetal status, 2 (15%) for arrest in cervical dilatation, and 1 (8%) for intraamnionic infection. Four patients (31%) successfully delivered vaginally.
CONCLUSION: Results showed a positive effect on the Bishop score during cervical ripening although further studies are needed to establish direct correlation.

Human ; Female ; Alprostadil ; Birth Weight ; Cervical Ripening ; Cervix Uteri ; Cesarean Section ; Diabetes Mellitus ; Dilatation ; Fetal Distress ; Hypertension ; Labor Stage, First ; Pregnancy