PURPOSE: Persistent pulmonary hypertension of the newborn (PPHN) is a potentially fatal disease. Inhaled iloprost, a stable analogue of prostacyclin, has recently been used as a therapeutic option. However, there are no clinical guidelines on the use of iloprost, specifically for neonates. This study aimed to suggest the use of inhaled iloprost as a rescue therapy for PPHN based on our experience.METHODS: The efficacy and adverse events of inhaled iloprost were evaluated prospectively in nine full-term neonates with PPHN. We monitored the following parameters: fraction of inspired oxygen (FiO₂), respiratory severity score (RSS), heart rate, and mean blood pressure.RESULTS: The inhalation dose was 1 to 2 µg/kg initially, and 4 to 8 inhalations per day were applied over 2 to 8 days, except in the case of one neonate who died 2 days after birth. Echocardiographic findings, changes in FiO₂, and RSS improved within the next 7 days in eight of the nine patients. Severe side effects on heart rate and blood pressure were not observed.CONCLUSION: Our experience suggests that inhaled iloprost can be used as a first-line treatment in newborn infants with PPHN when inhaled nitric oxide is not available. To the best of our knowledge, this report is the first prospective case series on the use of inhaled iloprost in PPHN.
Blood Pressure ; Echocardiography ; Epoprostenol ; Female ; Heart Rate ; Humans ; Hypertension, Pulmonary ; Iloprost ; Infant, Newborn ; Inhalation ; Nitric Oxide ; Oxygen ; Parturition ; Persistent Fetal Circulation Syndrome ; Prospective Studies

This study aimed to investigate the antihypertensive effect and possible mechanism of Dendrobium officinale flos on hypertensive rats induced by high glucose and high fat compound alcohol. The hypertensive models were successfully made by high-glucose and high-fat diet, with gradient drinking for 4 weeks, and then divided into model control group, valsartan (5.7 mg·kg⁻¹) positive control group and D. officinale flos groups (3，1 g·kg⁻¹). After 6 weeks of treatment, the blood pressure of rats was measured regularly. After the last administration, endothelin-1 (ET-1), thromboxane B₂ (TXB₂), prostacyclin (PGI₂) and nitric oxide (NO) were tested. Endothelial nitric oxide synthase (eNOS) expression and lesion status in thoracic aorta were detected. The vascular endothelium dependent dilation of the thoracic aorta was detected by the isolated vascular loop tension test. The results showed that D. officinale flos could significantly reduce systolic blood pressure and mean arterial pressure in hypertensive rats, inhibit the thickening of thoracic aorta and the loss of endothelial cells, reduce plasma content of ET-1 and TXB₂, and increase the content of PGI₂ and NO. After long-term administration, vascular endothelium dependent dilation of the thoracic aorta was significantly increased, and could be blocked by the eNOS inhibitor (L-NAME) and increase the expression of eNOS. Therefore, D. officinale flos has an obvious antihypertensive effect on high glucose and high fat compound alcohol-induced hypertensive rats. Its mechanism may be correlated with the improvement of vascular diastolic function by protecting vascular endothelial cells, and finally resist hypertension.
Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; Dendrobium ; chemistry ; Diet, High-Fat ; Drugs, Chinese Herbal ; pharmacology ; Endothelin-1 ; blood ; Endothelium, Vascular ; drug effects ; Epoprostenol ; blood ; Glucose ; Hypertension ; chemically induced ; drug therapy ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; T-Box Domain Proteins ; blood ; Vasodilation

OBJECTIVETo investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.

METHODSThe ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats.

RESULTSPreconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca sensitive-K channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently.

CONCLUSIONBAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca sensitive-K (BK and IK) channels in the corpus cavernosum.

Animals ; Area Under Curve ; Berberis ; chemistry ; Blood Pressure ; drug effects ; Cyclic GMP ; metabolism ; Epoprostenol ; pharmacology ; In Vitro Techniques ; Indomethacin ; pharmacology ; Male ; Models, Biological ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Penile Erection ; drug effects ; Phenylephrine ; pharmacology ; Plant Extracts ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Pressure ; Rabbits

Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group. The mRNA expression of miR-124 and the mRNA and protein expression of pyridoxal kinase (PDXK) were detected by quantitative real-time polymerase chain reaction and western blotting. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale. Brdu, neuron-specific enolase (NSE), neurofilament (NF) and microtubule-associated protein 2 (MAP2) were detected using immunohistochemistry. The expression levels of thyrotropin-releasing hormone (TRH), prostacyclin (PGI2) and gangliosides (GM) were measured using an enzyme-linked immunosorbent assay. PDXK was identified as the target gene of miR-124. The overexpressed miR-124 group exhibited higher miR-124 expression than the SCI, NC and si-PDXK groups. Compared with the SCI and NC groups, the PDXK expression was downregulated in the overexpressed miR-124 and si-PDXK groups, and the BBB scores were significantly increased 7, 21 and 35 days after transplantation. The double-labeled positive cell densities (Brdu+NSE/NF/MAP2) and the expression levels of TRH, PGI2 and GM in the overexpressed miR-124 group were significantly higher than those in the NC and SCI groups. These results indicated that miR-124 targeted PDXK to accelerate the differentiation of BMSCs into neurocytes and promote SCI repair.
Animals ; Blotting, Western ; Bone Marrow* ; Bromodeoxyuridine ; Cell Count ; Enzyme-Linked Immunosorbent Assay ; Epoprostenol ; Gangliosides ; Immunohistochemistry ; Intermediate Filaments ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stromal Cells* ; Microtubule-Associated Proteins ; Phosphopyruvate Hydratase ; Pyridoxal Kinase ; Rats* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Spinal Cord Injuries* ; Spinal Cord* ; Thyrotropin-Releasing Hormone

Investigating the effect of electrospun fiber diameter on endothelial cell proliferation provides an important guidance for the design of a fabric scaffold. In this study, we prepared biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) fibrous nonwoven mats with different fiber diameters ranged from 200 nm to 5 µm using the electrospinning technique. To control the fiber diameters of PLGA mats, 4 mixture solvents [hexafluoro-2-propanol, 2,2,2,-trifluoroethanol:dimethylformamide (9:1), 2,2,2,-trifluoroethanol:hexafluoro-2-propanol (9:1), chloroform] were used. Average diameters were 200 nm, 600 nm, 1.5 µm, and 5.0 µm, respectively. Stereoscopic structure and spatial characterization of fibrous PLGA mats were analyzed using atomic force microscopy and a porosimeter. The mechanical properties of PLGA mats were analyzed using a universal testing machine. The spreading behavior and infiltration of endothelial cells on PLGA mats were visualized by field emission scanning electron microscopy and hematoxylin and eosin staining. Cell proliferation on different PLGA fibers with different diameters was quantified using the MTT assay. Cells on 200 nm diameter PLGA mats showed rapid attachment and spreading. However, the cells did not penetrate the PLGA mat. Cells cultured on 600 nm and 1.5 µm diameter fibers could infiltrate the pores and cell proliferation was dramatically increased after 14 days. Secreted prostacyclin from endothelial cells on each mat was measured to examine the ability to inhibit platelet activation. This basic study on cell proliferation and fiber diameter with physical characterization provides a foundation for studies examining nonwoven fibrous PLGA mats as a tissue engineering scaffold.
Cell Proliferation ; Endothelial Cells* ; Eosine Yellowish-(YS) ; Epoprostenol ; Hematoxylin ; Microscopy, Atomic Force ; Microscopy, Electron, Scanning ; Nanofibers ; Platelet Activation ; Solvents ; Tissue Engineering*

OBJECTIVETo observe the effect of magnesium sulfate, Nifedipine Tablet (NT) combined Salvia Injection (SI) on endothelin-1 (ET-1), nitric oxide (NO), thromboxane A2(TXA2), prostacyclin I2(PG2), and hemorheology of preeclampsia patients.

METHODSTotally 704 preeclampsia patients were randomly assigned to the treatment group and the control group, 352 cases in each group. All patients were treated with magnesium sulfate combined NT (on the first day: slow intravenous injection of magnesium sulfate 5 g + intravenous dripping of magnesium sulfate injection 10 g + oral administration of NT 30 mg; on the second and third day, intravenous dripping of magnesium sulfate injection 10 g + oral administration of NT 30 mg), while those in the treatment group were dripped with SI additionally at 20 mL per day for 3 consecutive days. Before and after treatment plasma levels of endothelin-1 (ET-1), nitric oxide (NO), TXA2, PGi2, and hemorheology indicators [such as high blood viscosity (HBV), low blood viscosity (LBV), plasma viscosity (PV), erythrocyte rigidity index (ERI), fibrinogen (FIB)] of two groups were detected.

RESULTSCompared with the same group before treatment, serum levels of ET-1, TXA2, HBV, LBV, PV, ERI, and FIB decreased in the two groups after treatment (P <0. 05), but levels of NO and PG2 increased (P <0. 05). Compared with the control group in the same period, levels of ET-1, TXA2, HBV, LBV, PV, ERI, and FIB decreased in the treatment group after treatment (P <0. 05), but levels of NO and PGI2 increased (P <0. 05).

CONCLUSIONMagnesium sulfate, NT combined SI could effectively regulate the balance of ET-1/NO and TXA2/PGI2, and improve hemorheology of preeclampsia patients.

Drug Therapy, Combination ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelin-1 ; metabolism ; Epoprostenol ; metabolism ; Female ; Hemorheology ; Humans ; Injections ; Magnesium Sulfate ; administration & dosage ; pharmacology ; therapeutic use ; Nifedipine ; administration & dosage ; pharmacology ; therapeutic use ; Nitric Oxide ; metabolism ; Pre-Eclampsia ; drug therapy ; Pregnancy ; Salvia ; Tablets ; Thromboxane A2 ; metabolism

OBJECTIVETo investigate the effects of high-volume hemofiltration (HVHF) on hemodynamics, vasoactive factors, and vascular endothelial permeability in children with septic shock by a comparative analysis.

METHODSThirty-six children who were diagnosed with septic shock between January 2013 and September 2014 were randomly divided into control and observation groups (n=18 each). Children in the control group were treated with the standard-volume hemofiltration (SVHF), while children in the observation group were treated with HVHF. The hemodynamic indices and levels of vasoactive factors including 6-keto-prostaglandin F1α (6-keto-PGF1α), thromboxane B2 (TXB2), soluble E-selectin (sE-selectin), and endothelium-derived relaxing factor (EDRF) were determined before and after treatment. In addition, the effects of ultrafiltrate on endothelial cell permeability were assessed.

RESULTSCompared with the control group, the observation group had significantly higher mean arterial pressure, significantly higher blood oxygen saturation, and a significantly lower heart rate after treatment (P<0.05). The levels of TXB2 and sE-selectin were significantly lower in the observation group than in the control group (P<0.05), while the levels of 6-keto-PGF1α and EDRF were significantly higher in the observation group than in the control group (P<0.05). Compared with the control group, the ultrafiltrate significantly attenuated the transepithelial electrical resistance in the observation group (P<0.05).

CONCLUSIONSCompared with SVHF, HVHF is a more effective approach for improving the hemodynamics and levels of vasoactive factors and reducing the vascular endothelial permeability in children with septic shock.

Capillary Permeability ; Child ; Child, Preschool ; Epoprostenol ; physiology ; Female ; Hemodynamics ; Hemofiltration ; Humans ; Infant ; Male ; Shock, Septic ; physiopathology ; Thromboxane A2 ; physiology

Decreased exercise capacity after Fontan surgery is relatively common and the failure of the Fontan state gradually increases with age. However, there is no further treatment for patients with Fontan circulation. Pulmonary vasodilation therapy is an effective method to solve this problem because pulmonary vascular resistance is a major factor of the Fontan problem. Inhaled iloprost is a chemically stable prostacyclin analogue and a potent pulmonary vasodilator. We experienced two cases of Fontan patients treated with inhaled iloprost for 12 weeks. The first patient was an 18-year-old female with pulmonary atresia with an intact ventricular septum, and the second patient was a 22-year-old male with a double outlet right ventricle. Fifteen years have passed since both patients received Fontan surgery. While the pulmonary pressure was not decreased significantly, improved exercise capacity and cardiac output were observed without any major side effects in both patients. The iloprost inhalation therapy was well tolerated and effective for the symptomatic treatment of Fontan patients.
Adolescent ; Cardiac Output ; Double Outlet Right Ventricle ; Epoprostenol ; Female ; Fontan Procedure ; Humans ; Iloprost* ; Male ; Pulmonary Atresia ; Respiratory Therapy ; Vascular Resistance ; Vasodilation ; Ventricular Septum ; Young Adult

BACKGROUNDPrevious studies have shown that prostaglandins (PGs) dramatically stimulate healing processes in bone. However, the effect of prostaglandin I2 (PGI2) on fracture healing remains unclear. To investigate the effect of PGI2, a study on fracture healing process in closed tibia fractures was designed.

METHODSThirty-six Sprague-Dawley male rats were randomized into two groups. On the first day, their right tibias were fractured by three-point bending technique. The study group (n = 18) received a single injection of 10 µg/kg iloprost for 5 days, while the control group (n = 18) received saline solution in the same way. On the 7th, 14th and 28th days following the fracture, six rats were sacrificed and their right legs were harvested in each group. The progression of fracture healing was assessed for each specimen by the scores of radiography (by Lane-Sandhu) and histology (by Huo et al).

RESULTSOn the 7th day, the radiographic and histologic scores were equal. On the 14th day radiographic total score was 6 and histologic total score was 23 in the iloprost group, whereas radiographic total score was 11 and histologic total score was 33 in the control group. On the 14th day radiographic and histologic scores were significantly decreased in the iloprost group compared to the control group (P < 0.05). On the 28th day radiographic total score was 12 and histologic total score was 37 in the iloprost group, whereas radiographic total score was 15 and histologic total score was 40 in the control group. On the 28th day although there was a decrease in radiographic and histologic scores of the iloprost group acording to control group, it was not statistically significant (P > 0.05).

CONCLUSIONIloprost delays fracture healing in early stage in rats.

Animals ; Epoprostenol ; pharmacology ; Fracture Healing ; drug effects ; Fractures, Bone ; pathology ; Iloprost ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Tibial Fractures ; pathology ; Wound Healing ; drug effects

OBJECTIVETo explore effects of beraprost sodium (BPS) on the metabolism of extracellular matrix (ECM) in rat mesangial cells cultured in the presence of high glucose and the possible mechanism.

METHODSRat mesangial cells were cultured in the presence of high glucose with or without BPS for 24 or 48 h. The levels of transforming growth factor β1 (TGFβ1), fibronectin (FN) and matrix metalloproteinase-2 (MMP-2) protein in the culture supernatants were measured by enzyme-linked immunosorbent assay, and photoshop-Smad3 was detected by Western blotting.

RESULTSCompared with the cells in normal glucose, the cells cultured in the presence of high glucose for 24 and 48 h showed significantly increased TGFβ 1 and FN protein expression and lowered MMP-2 protein expression (P<0.01). Compared with the cells cultured in high glucose, BPS exposure at the concentration of 1, 2, and 5 µmol/L for 24 and 48 h significantly lowered TGFβ 1 protein expression (P<0.01), and at 2 and 5 µmol/L, BPS significantly decreased FN protein expression and increased MMP-2 protein expression in high glucose-induced cells (P<0.05). High glucose exposure also significantly increased the expression phosphorylated Smad3 (P<0.01), which was lowered by BPS treatment at 2 and 5 µmol/L (P<0.01).

CONCLUSIONBPS can regulate ECM metabolism in rat mesangial cells cultured in high glucose by inhibiting TGFβ 1/Smad3 pathway, suggesting the beneficial effects of BPS in preventing and treating diabetic nephropathy.

Animals ; Cell Line ; Cells, Cultured ; Diabetic Nephropathies ; Enzyme-Linked Immunosorbent Assay ; Epoprostenol ; analogs & derivatives ; pharmacology ; Extracellular Matrix ; metabolism ; Fibronectins ; metabolism ; Glomerular Mesangium ; cytology ; Glucose ; Matrix Metalloproteinase 2 ; metabolism ; Mesangial Cells ; drug effects ; Rats ; Transforming Growth Factor beta1 ; metabolism