Uso de treprostinil sistémico en una paciente con hipertensión pulmonar grave, sin respuesta a la máxima terapia disponible / Use of treprostinil in a patient with a severe pulmonary arterial hypertension no responding to the maximal therapy available

En los pacientes con Hipertensión Arterial Pulmonar (HAP) de alto riesgo, en clase funcional (CF)IV, la terapia específica debe ser combinada y debe incluir una prostaciclina (PGI2) de uso sistémico en espera de trasplante bipulmonar (TBP). En el sistema público la única PGI2 disponible para asociar a Sildenafil y algún inhibidor de endotelina (Ambrisentan o Bosentan) es Iloprost nebulizado, que si bien es efectiva, no logra estabilizar los casos graves con severa disfunción del ventrículo derecho (VD). Se presenta el primer caso en el Instituto del Tórax, centro de referencia nacional de HAP, del uso de treprostinil en una paciente de 24 años con HAP grave e indicación de TBP. Treprostinil es un análogo sintético de PGI2 de uso subcutáneo en dosis desde 1 a 40 ng/kg/min. La paciente presentaba una situación de extrema gravedad: CF IV, distancia recorrida en el test de caminata de 6 min (DRTC 6 min) < 300 m,derrame pericárdico y severa disfunción del VD con TAPSE (índice de disfunción del VD) de 13 cm/s asociado a ProBNP >2.500 pg/ml. Luego de 6 meses de hospitalización en intermedio, terapia triple (Sildenafil, Ambrisentan e Iloprost nebulizado) asociado a O2,diuréticos y milrinona, logró ser dada de alta a las 3 semanas del inicio de treprostinil, regresando al trabajo a los 2 meses y estabilizando su condición en CF III, con DRTC 6 min > 440 m, mejoría de la función del VD(TAPSE 19). El ProBNP persistió elevado, 1.491 pg/ml, indicando que su enfermedad es grave y progresiva; sin embargo, ha logrado un nivel de estabilidad clínica que le permite una adecuada vida de relación familiar y laboral.

In high risk Pulmonary Arterial Hypertension (PAH) patients with functional class (FC) IV, specific therapy must be combined and must include systemic prostacyclin (PGI2), meanwhile they are enlisted for double lung transplant (DLT). In Chilean Public Health System, nebulized Iloprost is the only PGI2 available to combine with Sildenafil and either Ambrisentan or Bosentan as endothelin receptor antagonist. This association is not enough for severe cases with right ventricular (RV) dysfunction. The first case from the National Institute of Thorax as a referral center is presented now in a 24 years-old lady treated with treprostinil. She has severe PAH with DLT indication. Treprostinil is a PGI2 analog, for subcutaneous use in a dose from 1 to 40 ng/kg/min. She was extremely sick, with FC IV, she walked < 300 m at 6 min walking test (6 MWT), presented pericardial effusion and severe RV dysfunction, with TAPSE (echocardiography index for RV dysfunction)=13 cm/s, ProBNP > 2,500 pg/ml. Six months after being at intensive care unit with triple therapy (Sildenafil, ambrisentan and nebulized Iloprost) plus oxygen, diuretics and milrinone, she was finally discharged after receiving a 3 weeks treprostinil course. She came back to work two months later and her condition was more stable: FC III, she walked > 440 m at 6MWT, with a significant improvement in RV function with TAPSE = 19. Although ProBNP decreased to 1,491pg/ml, it was still high, pointing out the progressive nature of her disease. However, she met a better clinical condition which allows her to reach a much better quality of life from a personal, familial and social point of view.

Análogos de prostaglandinas I2 (epoprostenol y treprostinil) para el tratamiento de la hipertensión pulmonar refractaria secundaria a displasia broncopulmonar en un lactante / Prostaglandin 12 analogs (epoprostenol and treprostinil) as a treatment for refractory bronchopulmonary dysplasia-induced pulmonary hypertension in an infant

La hipertensión pulmonar es una complicación frecuente de la displasia broncopulmonar. A pesar de su alta incidencia, existen pocos tratamientos disponibles. El epoprostenol y el treprostinil son análogos de las prostaglandinas I2, que activan la adenilato ciclasa e incrementan el adenosín monofosfato cíclico en las células de la musculatura lisa de la arteria pulmonar y pueden resultar eficaces en el tratamiento de estos pacientes. Se presenta el caso de un prematuro de extremado bajo peso con hipertensión pulmonar secundaria a displasia broncopulmonar grave, no respondedora a óxido nítrico inhalado y sildenafilo, que fue tratado con análogos de prostaglandinas I2. En nuestro paciente, este tratamiento evidenció mejoría clínica y ecocardiográfica significativa tras varias semanas de tratamiento.

Pulmonary hypertension is a common complication of bronchopulmonary dysplasia, with a high mortality rate. Despite the high incidence of pulmonary hypertension, there are few available treatments. Epoprostenol and treprostinil are prostaglandin I2 analogs that activate adenylate cyclase and increase cyclic adenosine monophosphate in the pulmonary arterial smooth muscle cells. Therefore, they may be an effective treatment for these patients. We report the use of prostaglandin I2 analogs in an extremely low birth weight preterm baby with severe bronchopulmonary dysplasia associated with pulmonary hypertension non-responding to inhaled nitric oxide and sildenafil. In our patient this treatment resulted in remarkable clinical and echocardiographic improvement, evident after a few weeks of treatment.

Inhaled Iloprost as a First-Line Therapy for Persistent Pulmonary Hypertension of the Newborn

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.

Protective effects of baicalin on experimental myocardial infarction in rats

Abstract Objective: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. Methods: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. Results: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). Conclusion: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.

The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

Beneficial Effect of Berberis amurensis Rupr. on Penile Erection / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Preconstricted 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.</p><p><b>CONCLUSION</b>BAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca sensitive-K (BK and IK) channels in the corpus cavernosum.</p>

Antihypertensive effect and mechanism of Dendrobium officinale flos on high-blood pressure rats induced by high glucose and high fat compound alcohol / 中国中药杂志

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.

Lentivirus-mediated microRNA-124 gene-modified bone marrow mesenchymal stem cell transplantation promotes the repair of spinal cord injury in rats

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.

Growth Behavior of Endothelial Cells According to Electrospun poly(D,L-Lactic-Co-Glycolic Acid) Fiber Diameter as a Tissue Engineering Scaffold

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.

Interrelación del equilibrio tromboxano A2-prostaciclina y su modificación cuando se ingiere aspirina / Interrelation of the balance tromboxano A2-prostaciclina and its modification when aspirin is ingested

Introducción: la aspirina, es usada por su acción antiinflamatoria, analgésica, antipirética y antiagregante plaquetaria. El conocimiento del metabolismo del ácido araquidónico es fundamental para el estomatólogo que basa su trabajo en diagnosticar y tratar procesos inflamatorios en tejidos bucodentales, también por su condición de cirujano debe estar alerta en no realizar intervenciones quirúrgicas en pacientes que estén tomando aspirina, por interrumpir este medicamento la agregación plaquetaria, importante paso de la hemostasia normal. Objetivo: interpretar la interrelación hemostática del tromboxano A2 y la prostaciclina en condiciones fisiológicas, y el resultado de su modificación cuando se ingiere aspirina. Método: PubMed fue empleada como fundamental fuente de búsqueda, que incluyó el conocimiento sobre el fármaco aspirina, la interacción del tromboxano y la prostaclina, y la acción que sobre el equilibrio de estos productos ejerce la aspirina; también se revisaron HINARI, LILACS y Medline. Desarrollo: el ácido araquidónico es un ácido graso poliinsaturado de 20 átomos de carbono (ácido 5, 8, 11, 14-eicosatetraenoico) que procede directamente de la dieta. La relación recíproca entre PG-I2 y el TxA2 constituye un mecanismo finamente equilibrado que sirve para regular la función plaquetaria del ser humano. La utilidad de la aspirina en los pacientes expuestos a trombogénesis se debe, en gran parte, a su capacidad para inhibir la síntesis del TxA2, agente derivado del ácido araquidónico, elemento que se encuentra esterificado a los fosfolípidos de la membrana plaquetaria. El óxido nítrico, igual que la PG-I2, actúa también como vasodilatador e inhibidor de la agregación plaquetaria. Conclusiones: los pacientes que acuden al estomatólogo y por prescripción facultativa están tomando aspirina, tienen su sistema plaquetario inhibido y no pueden sintetizar tromboxano. El proceder quirúrgico por parte del estomatólogo en un paciente que esté ingiriendo aspirina lo expone al desarrollo de hemorragia de causa iatrogénica(AU)

Introduction: aspirin is used by its arachidonic acid is fundamental for the dentist that bases its work on diagnosis and treatment of inflammatory processes, also for its surgeon condition he should be alert to do not carry out surgical interventions in patients that are taking aspirin, because this drug interrupts platelet aggregation, important step of the normal hemostasis. Objective: to interpret the hemostatic interrelation of the tromboxano A2 and the prostaciclina in physiologic conditions and the result of their modification when aspirin is ingested. Method: it was employee as fundamental search source the PubMed, other databases also revised they were HINARI, LILACS, Medline. Was carried out a search that included the knowledge on the drug aspirin, the interaction of the tromboxano and the prostaclina, and the action that it has more than enough the balance of these products it exercises the aspirin. Development: the arachidonic acid is a polyunsaturated fatty acid of 20 atoms of carbon (5, 8, 11, 14-eicosatetraenoic acid) that proceeds directly from diet. The reciprocal relationship between PG-I2 and TxA2 constitutes a finely balanced mechanism that is good to regulate the human being's platelet function. The utility of aspirin in patients exposed to thrombogenesis is largely due to its capacity to inhibit the synthesis of the TxA2, agent derived from arachidonic acid, which is esterified to the phospholipids of the platelet membrane. Nitric oxide, the same as the PG-I 2, also acts as vasodilator and inhibitor of the platelet aggregation. Conclusions: the patients that go to the dentist and for medical prescription are taking aspirin, have their platelet system inhibited and cannot synthesize tromboxane. Surgical processes performed by the dentist in a patient that is ingesting aspirin exposes him to the development of hemorrhage of yatrogenic cause(AU)

Effect of Magnesium Sulfate, Nifedipine Tablet Combined Salvia Injection on ET-1/NO, TXA2/PGI2 and Hemorheology of Preeclampsia Patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Totally 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.</p><p><b>RESULTS</b>Compared 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).</p><p><b>CONCLUSION</b>Magnesium sulfate, NT combined SI could effectively regulate the balance of ET-1/NO and TXA2/PGI2, and improve hemorheology of preeclampsia patients.</p>

Impacts of high-volume hemofiltration on hemodynamics and vascular endothelial permeability in children with septic shock / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Thirty-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.</p><p><b>RESULTS</b>Compared 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).</p><p><b>CONCLUSIONS</b>Compared 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.</p>

Iloprost inhibits fracture repair in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous 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.</p><p><b>METHODS</b>Thirty-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).</p><p><b>RESULTS</b>On 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).</p><p><b>CONCLUSION</b>Iloprost delays fracture healing in early stage in rats.</p>

Inhaled iloprost for the treatment of patient with Fontan circulation / 소아과

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.

O endotélio disfuncionante na hipertensão arterial e no tabagismo / Dysfunctional endothelium in hypertension and smoking

Disfunção endotelial (DE) caracteriza qualquer alteração de atividadenormal do endotélio incluindo atividade vasomotora, proliferaçãocelular, adesão/agregação plaquetária, permeabilidade vascular e a interaçãoleucócitos/parede vascular. Contudo, em repouso o leito arterialexibe um estado basal de vasoconstrição (tônus vascular) modulado pormecanismos de controle centrais (sistema nervoso-simpático), periféricos(sistema renina-angiotensina-aldosterona) e um mecanismo local(endotelial) cuja potência é superior às anteriores. DE na hipertensãoestá relacionada à diminuição da biodisponibilidade de NO por reduçãoda síntese e liberação pela sintase endotelial do óxido nítrico (eNOS)influenciada por fatores genéticos e ambientais como hipóxia, hipofluxo,forças de cisalhamento, redução do substrato L-arginina e seuscofatores, ou inativação do NO resultado da sua ligação com diferentesmoléculas hemoglobina, albumina e, principalmente, sua interação comespécies reativas de oxigênio (estresse oxidativo). DE na hipertensãopode, ainda, estar associada à liberação de substâncias vasoconstritorasderivadas do endotélio como trornboxano-Aç, prostaglândina-Hj,endotelina-l e angotensina-Il. Tabagismo aumenta o risco de eventoscardiovasculares, principalmente quando associado à hipertensão.Nicotina estimula a liberação de catecolarninas e promove lesões noendotélio vascular. Radicais livres e compostos aromáticos diminuema síntese de NO, prejudicando a vasodilatação endotélio-dependente.Tabagismo favorece o crescimento celular por estimulação de fatoresde crescimento do endotélio vascular e inativação do NO por aumentodo estresse oxidativo. Aumento da oxidação das lipoproteínas debaixa densidade (LDL) em fumantes tem efeito sinérgico na adesão emigração de monócitos. Todos esses efeitos deletérios do tabagismono leito vascular também são observados, embora em menor extensão,em tabagistas passivos...

Endothelial dysfunction (ED) characterizes ali changes in the normalactivity ofthe endothelium including vasomotor activity, cell proliferation,platelet adhesion and aggregation, vascular permeability andleukocyte-vascular wall interactions. However, at rest, the arterialbed exhibits a baseline state of vasoconstriction (vascular tone) whichis modulated by central control (sympathetic nervous system) andperipheral mechanisms (Renin angiotensin-aldosterone system) anda local mechanism (endothelial); the latter is the most potent. ED inhypertension is related to decreased bioavailability of nitric oxide(NO) due to its reduced synthesis and release by endothelial nitricoxide synthase (eNOS) regarding genetic and environmental factorssuch as hypoxia, decreased blood flow, shear forces, diminishedL-arginine substrate and its cofactors and NO inactivation as a resultof its binding to different molecules including hemoglobin, albuminand, mainly, its interaction with reactive oxygen species (oxidativestress). ED in hypertension can also be linked to the release of endothelium-derived vasoconstricting substances such as thromboxane-Ai,prostaglandin-H2, endothelin-l and angiotensin-Il. Smoking increasesthe risk of cardiovascular events especially when associated withhypertension. Nicotine stimulates catecholamine release and causesvascular endothelium injury. Free radicais and aromatic compoundsreduce NO synthesis, impairing endothelium-dependent vasodilation.Smoking promotes cell growth by stimulating vascular endotheliumgrowth factors and NO inactivation by increasing oxidative stress.The increased oxidation of low-density lipoproteins ir smokers hasa synergistic effect on monocyte adhesion and migration. All thesedeleterious effects of smoking on the vascular bed are also observed,albeit at a lesser extent, in passive smokers...

Advances in superenzyme gene therapy in penile rehabilitation / 中华男科学杂志

Erectile dysfunction (ED) is an almost unavoidable complication of radical prostatectomy. At present, though the concept of penile rehabilitation (PR) is accepted by most clinicians, the outcomes of erectile function recovery vary widely. Prostacyclin (PGI2) is a prostanoid and a main vasoprotectant which induces smooth muscle relaxation, but not used for replacement therapy because of its high unstability. SuperEnzyme is capable of continuous, specific and targeted promotion of PGI2 synthesis, and helps PR in ED patients after radical prostatectomy. SuperEnzyme gene therapy has a promising prospect for PR and the management of ED. This review updates SuperEnzyme gene therapy in PR.

Clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure induced by chronic glomerulonephritis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure caused by chronic glomerulonephritis.</p><p><b>METHODS</b>Sixty-three patients with chronic renal failure due to chronic glomerulonephritis, after receiving a 2-week-long conventional treatment, were randomly divided into alprostadil group (n=20, with alprostadil injection at 10 µg/d for 2 weeks), sequential treatment group (n=21, with alprostadil injection at 10 µg/d for 2 weeks and oral beraprost sodium at 20 µg three times a day for 12 weeks), and strengthened sequential treatment group (n=22, with alprostadil injection at 20 µg/d for 2 weeks and a double dose of oral beraprost sodium for 12 weeks). Urinary albumin excretion rate (UAER), cystatin C (Cys C), blood urea nitrogen, creatinine, fibrinogen, D-dimer, prothrombin time (PT), and platelets were tested before and after the treatment, and the changes in urinary albumin discharge rate, serum creatinine, and glomerular filtration rate were determined.</p><p><b>RESULTS</b>The patients in strengthened sequential treatment group showed a significantly decreased change rate of urinary albumin discharge rate (P<0.01) than those in the other two groups. In the two sequential treatment groups, especially the strengthened treatment group, the change rate of glomerular filtration rate increased significantly compared with that in alprostadil group (P<0.01). Strengthened sequential treatment resulted also in significantly decreased increment of serum creatinine compared that in the other 2 groups (P<0.01). After 14 weeks of treatment, fibrinogen and D-dimer were decreased in all the 3 groups (P<0.05) to a comparable level between the 3 groups (P>0.05), and prothrombin time (PT) or platelet showed no significant changes (P>0.05).</p><p><b>CONCLUSION</b>Sequential treatment with alprostadil and beraprost sodium can improve the glomerular filtration rate and decrease urine albumin excretion rate, serum creatinine increase rate, and lower blood fibrinogen and D-dimer levels, thus delaying the progression of chronic renal failure caused by chronic glomerulonephritis. This therapy shows a dose-related effect with good clinical safety.</p>

Effects of beraprost sodium on extracellular matrix metabolism in cultured rat mesangial cells induced by high glucose / 南方医科大学学报

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Rat 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.</p><p><b>RESULTS</b>Compared 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).</p><p><b>CONCLUSION</b>BPS 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.</p>

Minimally modified LDL induced impairment of endothelium-dependent relaxation in mesenteric arteries of mice / 药学学报

This study is to investigate the impairment and possible mechanism of endothelium-dependent relaxation of mice mesenteric arteries induced by mmLDL. Wire myography was employed to examine endothelial function of mesenteric arteries. Ultramicrostructure of mesenteric vascular beds were detected by transmission electron microscope. The results showed that endothelium cell edema and peeling, vascular elastic membrane fracture traces in mmLDL group. Endothelium-dependent relaxation was decreased in a time-dependent and dose-dependent manner by using mmLDL, compared with normal arteries. In endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation, the Rmax and pIC50 were decreased from (63 +/- 5) % and 6.42 +/- 0.09 of normal saline control to (31 +/- 3) % and 5.67 +/- 0.07 in mmLDL group (P < 0.001, P < 0.001), respectively. In nitric oxide (NO)-mediated relaxation, the Rmax and pIC50 were decreased from (45 +/- 4) % and 5.93 +/- 0.08 in normal saline control to (32 +/- 4) % and 5.43 +/- 0.11 in mmLDL group (P < 0.05, P < 0.01), respectively. There is no significant alteration of prostacyclin I2 (PGI2) pathway between these two groups. In conclusion, mmLDL induced the impairment of the ultramicrostructure of mesenteric vascular endothelium cell as well as the endothelium-dependent relaxation. The latter includes the dysfunction of NO- and EDHF pathway mediated endothelium-dependent relaxation.