Expression changes of prostacyclin and thromboxane in blood of rats with tail vibration / 环境与职业医学

Background Long-term exposure to hand-transmitted vibration can lead to hand-arm vibration syndrome, one manifestation of which is impaired peripheral blood circulation in the arms. Altered expressions of prostacyclin I2 (PGI2) and thromboxane A2 (TXA2) in blood may be one of the important mechanisms of vibration-induced hand-arm vibration syndrome. Objective To reveal the effects of rat tail vibration on the expressions of PGI2 and TXA2 in plasma, and to establish the correlation between the change of rat plasma PGI2 to TXA2 ratio and rat tail vibration. Methods Fifty SPF-grade male SD rats were randomly divided into five groups: control group, 1 d exposure group, 3 d exposure group, 7 d exposure group, and 14 d exposure group, with 10 rats in each group. The rats were placed in rat immobilizes on a immobilization table, and the rats' tails were connected to a shaker and fixed with medical tape. There was no overlap between the immobilizes and between the rats' tails by no contact between the immobilization table and the shaker. The exposure dose was 125 Hz, 5.9 m·s−2, 4 h·d−1, and the vibration direction was linear vertical vibration. Abdominal aortic blood was taken at the end of vibration exposure, and the expressions of PGI2, TXA2, and their hydrolysates 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TXB2) were measured by enzyme-linked immunosorbent assay, and the 6-keto-PGF1α/TXB2 values were calculated. Spearman rank correlation was used to analyze whether the expression of vascular factors correlated with the accumulated time of vibration. Results The expression levels of plasma 6-keto-PGF1α were (896.12±124.37), (1068.13±119.41), (1215.26±122.64), and (1317.94±106.54) ng·L−1 in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, which were higher than that in the control group, (830.60±109.47) ng·L−1 (P<0.001). The PGI2 expression levels were (86.49±2.40), (107.90±2.65), (114.02±2.16), and (126.95±1.94) ng·L−1 in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, all higher than (60.09±2.11) ng·L−1 in the control group (P＜0.001). The expression levels of TXB2 were (132.14±4.10), (145.52±4.09), (179.91±4.98), and (204.10±3.22) ng·L−1 in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, which were higher than that in the control group, (106.08±3.26) ng·L−1 (P<0.001). The expression levels of plasma TXA2 were (211.99±3.24), (236.33±3.88), and (245.45±4.23) ng·L−1 in rats in the 3 d, 7 d, and 14 d groups, respectively, which were all elevated compared with (174.79±4.19) ng·L−1 in the control group (P<0.001). Compared with the control group, the 6-keto-PGF1α/TXB2 values were decreased in the 7 d and 14 d groups (P<0.05). The 6-keto-PGF1α, PGI2, TXB2, and TXA2 expressions were positively correlated with vibration accumulation time (r=0.84, 0.84, 0.80, 0.84, P<0.001) and the 6-keto-PGF1α/TXB2 values were negatively correlated with vibration accumulation time (r=-0.24, P=0.003). Conclusion Local exposure of rat tail to vibration could increase the expressions of PGI2 and TXA2 in blood, and the elevated expressions show a dose-effect relationship with the duration of vibration exposure, but the PGI2/TXA2 tends to decrease with the accumulation of vibration exposure.

Application of selexipag in the treatment of pulmonary hypertension / 中国药房

Selexipag i s a kind of oral highly selective prostacyclin （IP）receptor agonist ，which can inhibit the contraction and proliferation of pulmonary artery smooth muscle cells. Because of its good patient compliance and high receptor affinity ，it is currently used in the treatment of pulmonary hypertension （PH）. This article reviews the mechanism of action ，pharmacokinetics/ pharmacodynamics and application of selexipag in the treatment of PH. The results show that selexipag alone or in combination with endothelin receptor antagonists and （or）phosphodiesterase inhibitors can effectively reduce the risk of worsening/death events ， delay disease progression ，and improve patients ’life quality in patients with adult pulmonary arterial hypertension （PAH）of WHO cardiac function Ⅱ-Ⅲ grade. However ，its application in children with PAH and patients with chronic thromboembolic PH needs further exploration.

Effects of prostacyclin on the development of kidney and vascular system in mice / 中华肾脏病杂志

Objective:To explore the role of prostacyclin (PGI 2) in the development of kidney and vascular system in mice. Methods:The prostacyclin synthase ( PGIS) knockout model was established in C57BL/6J mice. The effects of PGIS knockout on the survival rate of mice were observed by genotyping analysis. The effects of PGIS knockout on the development of kidney and vascular system in mice were observed by hematoxylin and eosin staining and periodic acid-Schiff staining. The morphological changes of kidneys in PGIS knockout mice were observed. Blood urea nitrogen was tested to evaluate the function of kidney in mice. Real-time quantitative PCR was used to analyze the effect of PGIS knockout on the mRNA expression of prostaglandin synthetase PGES and TXAS. The expression of PGIS in vascular system was observed by immunofluorescence staining. The blood pressure and heart rate of mice were measured by the tail-cuff method. Results:Most of the systemic complete PGIS knockout ( PGIS-/-) fetal mice sacrificed. The kidneys of PGIS-/- fetal mice developed abnormally, which showed sparse interstitial, abnormal tissue differentiation, lengthened renal vesicle, and significant decrease in the number of "S" -shape bodies ( P<0.01). The kidneys of PGIS-/- mice showed tissue atrophy, surface irregularities and cyst formation. Blood urea nitrogen level in the PGIS-/- mice was significantly higher than that in the wild type ( PGIS+/+) mice [(36.89±5.39) mmol/L vs (5.07±0.69) mmol/L, n=3, P<0.01]. There was no significant difference in the mRNA expression of PGES and TXAS between PGIS+/+ mice and PGIS-/-mice. PGIS was widely expressed in renal vascular endothelial cells and smooth muscle cells of PGIS+/+ mice. Vascular system developed abnormally, which showed loss of smooth muscle layer, width of subendothelial loose layer, thinning of the pipe wall, and discontinuity of the inner elastic plate in PGIS+/- mice. There was no significant difference in the blood pressure and heart rate between PGIS systemic half-knockout ( PGIS+/-) mice and PGIS-/- mice. Conclusion:PGIS plays an important role in the development of kidney and vascular system in mice.

Effect of chronic intermittent hypobaric hypoxia on relaxation of aorta and mechanisms in developing rats / 中国药理学通报

Aim To investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on relaxation of thoracic aorta rings in male developing rats and the underlying mechanisms. Methods Male neonatal Spra-gue-Dawlay ( SD) rats were randomly divided into eight groups respectively: CIHH treatment group (CIHH), group of one-week post-CIHH (CIHH-pl), group of two-week post-CIHH ( CIHH-p2 ) , group of three-week post-CIHH (CIHH-p3 ) , control group for CIHH (Con), control group for CIHH-pl (Con-1), control group for CIHH-p2 ( Con-2) and control group for CIHH-p3 (Con-3 ). Rats in CIHH groups were put into a hypobaric chamber with the mother rats 1 ~ 3 days before the birth to get a hypobaric hypoxia exposure mimicking 3 km altitude for 42 days, 5 hours daily. Rats in control groups were kept in the same environment as CIHH rats except hypoxia exposure. After anaesthetized with pentobarbital sodium (50 mg • kg-1 i. p. ), the thorax of rats was opened and thoracic aorta rings were made. The artery rings were placed in the bath chamber filled with K-H solution, and the relaxation of artery rings was recorded under normoxia or a-cute hypoxia conditions, respectively. Results (1) Under normoxia condition, the acetylcholine ( ACh)-induced relaxation of thoracic aorta increased obviously in CIHH groups compared with corresponding Con groups ( P < 0. 05 ). ( 2 ) The enhancing effect of CIHH treatment on thoracic aorta could be maintained for at least three weeks (P < 0. 05). (3 ) Under acute hypoxia condition, ACh-induced relaxation of thoracic aorta in each group decreased obviously, but the decrease in CIHH groups was significant less than that in Con groups ( P < 0.05 ). (4) The enhancement of CIHH on relaxation of thoracic aorta could be reversed by indomethacin (Indo), a cyclooxygenase inhibitor, glibenclamide (Gli), a KATP blocker, and Tempo, a free radical scavenger. Conclusions CIHH augments endothelium-dependent relaxation in thoracic aorta of developing rats. Also, CIHH can antagonize the inhibition of acute hypoxia on relaxation of thoracic aorta. The enhancing effect of CIHH treatment may be related with the increase of prostacyclin, the opening of KATP and free radical production.

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.

Effects of traditional Chinese medicine syndrome differentiation quadruple therapy on serum vascular active substance in patients with acute pancreatitis / 中国中西医结合急救杂志

Objective To observe the effects of traditional Chinese medicine (TCM) syndrome differentiation quadruple therapy on serum thromboxane A2 (TXA2), prostacyclin (PGI2) and platelet activating factor (PAF) levels in patients with acute pancreatitis (AP). Methods Ninety patients with AP admitted to the First Affiliated Hospital of Henan University of TCM from January 2016 to March 2017, and they were divided into an observation group and a control group according to the random numbers generated by computer inpatients, 45 cases in each group. The control group was given routine treatment of western medicine, and the observation group was given TCM syndrome differentiation quadruple therapy according to the patient's disease individual situation and on the basis of western medicine treatment. The TCM syndrome differentiation quadruple therapy included the following methods: intragastric administration of TCM decoction [gastrointestinal excess heat syndrome (rhubarb, sodium sulfate, aurantii fructus immaturus, magnolia bark, etc.), damp heat syndrome of liver and gallbladder (radix bupleuri, aurantii fructus immaturus, baical skullcap root, rhubarb, etc.), each group of above agents immersed in water and decocted to make juice 400 mL, once 100 mL taken orally, every 4 hours]; retention enema with TCM decoction [rhubarb, magnolia bark, aurantii fructus immaturus, sodium sulfate (dissolved) etc, each dose of agents forming decoction 400 mL, 200 mL taken for proctoclysis, once every 6 hours]; Chinese medicine package (boswellin, myrrha, dandelion, coptidis rhizoma and so on crushed and mixed with honey, then applied to the body surface of the pancreas and its periphery, 1 dose each time for 4 hours, once a day ); intravenous drip of blood-activating and stasis-resolving TCM (Dengzhanhuasu injection 100 mg added to 5% glucose solution 250 mL for intravenous drip). The times of disappearance of abdominal distension, abdominal pain, and the recovery times of bowel sound, blood amylase, lipase, C-reactive protein (CRP), white blood cell count (WBC) levels to normal were compared between the two groups; the modified CT severity index (MCTSI) score and the changes of serum TXA2, PAF and PGI2 levels were observed before and after treatment in the two groups. Results The abdominal pain and abdominal distension disappearance times in observation group were shorter than those in control group [abdominal pain (days): 5.07±1.88 vs. 6.02±1.89, abdominal distension (days): 3.50±1.49 vs. 4.40±1.53, both P < 0.05]; the recovery times of bowel sounds, WBC, CRP, amylase and lipase to normal were shorter than those of the control group [bowel sounds (days): 4.05±1.79 vs. 5.00±1.55, WBC (days): 3.93±1.49 vs. 5.98±2.90, CRP (days): 6.17±2.46 vs. 7.92±2.84, blood amylase (days): 3.5 (3.0, 5.0) vs. 5.0 (3.0, 5.5), lipase (days): 5.0 (3.0, 7.0) vs. 6.5 (5.0, 9.0), all P <0.05]; the scores of MCTSI in the two groups were lower than those before treatment and the degree of decrease in the observation group was more significant than that in the control group [2 (0, 4) vs. 4 (0, 6), P < 0.05]. The TXA2 and PAF levels of the two groups were significantly lower than those before treatment and the level of PGI2 was significantly higher than that before treatment; after treatment for 3 days, the differences between the two groups showed statistical significance and on the 7th day after treatment, the degrees of improvement in observation group were more obvious than those of the control group [TXA2 (ng/L): 276.81±31.48 vs. 345.42±47.27, PAF (ng/L): 72.65±17.61 vs. 89.77±15.59, PGI2 (ng/L): 104.43±18.67 vs. 94.37±17.91, all P < 0.05]; on the 14th day after treatment, the values of the two groups were very close and there were no statistically significant differences (all P >0.05). Conclusions The TCM differentiation syndrome quadruple therapy for treatment of AP is beneficial to the disappearance of clinical symptoms of patients with different syndromes, recovery of abnormal signs and improvement of laboratory indexes, and its early use can significantly reduce the serum levels of TXA2, PAF and increase the level of PGI2 in patients with AP.

Study on the ADR Mechanism of Conjunctival Hyperemia in Model Rats with Prostacyclin-induced High Intraocular Pressure / 中国药房

OBJECTIVE:To study the ADR mechanism of conjunctival hyperemia in model rats with prostacyclin-induced high intraocular pressure. METHODS:50 rats were randomly divided into normal control group,model group,prostacyclin low-dose, medium-dose,high-dose groups(100,200,400 mg/kg),10 in each group. Except for normal control group,right eyes of rats in other groups were established high intraocular pressure model,dropping corresponding medicine once a day,for 1 week. After last administration,the right eyes cornel peripheral corneal endothelial cells of rats in each group were isolated in vitro and cultured. Vascular endothelial cell viability,cell apoptosis and proliferation-related factor(Ki-76),apoptosis-related factors(Bad,Bax),in-hibito of apoptosis-related factors (Bcl-2,Bcl-xl) protein expressions were detected. RESULTS:Compared with normal control group,vascular endothelial cell viability in model group were obviously decreased;apoptosis rate was obviously increased;Bad, Bax protein expressions were obviously enhanced;Bcl-2,Bcl-xl,Ki-76 protein expressions were obviously weakened,with statisti-cal significances (P0.05). CONCLUSIONS:Prostacyclin may cause conjunctival hyperemia through promoting the apoptosis of cornel peripher-al corneal endothelial cells of model rats with high intraocular pressure and decreasing the cell viability.

The effects of Celecoxib on human brain microvascular endothelial cells release 6-keto-PGF1α and TXB2 and apoptosis after radiation / 中华放射肿瘤学杂志

Objective To investigate the effect of Celecoxib on human brain microvascular endothelial cells release6-keto-PGF1α,TXB2 and apotosis after irradiation.Methods The logarithmic growth phase cells were divided into control groups (Con),simple irradiation (IR) groups and combination groups (IR+C).CCK-8 and clone formation experiment were used to evaluate the effects of radiosensitivity and toxicity of celecoxib.The results were observed atthe time point of 6 h,12 h,24 h,48 h after irradiation.ELISA was used to test the contents of 6-keto-PGF1α and TXB2,which metabolized by PGI2 and TXA2 from culture medium after irradiation at different time points in different groups.TXB2/6-keto-PGF1αratios were calculated.Annexin V-FITC/PI double staining method was used to measure the apoptosis rates at different time points in different groups.Western blot was used to measure the protein expression.Paired t test difference.Results Compared with simple irradiation group,there were no significant radiosensitivity (SER=0.96) in combination groups incubated with30 μmol/L of celecoxib.Compared with the control group,the ratio of TXB2/6-keto-PGF1αincreased at each time point in IR and IR+C (P<0.05),and the apoptosis rates increased (P<0.05).Cox-2,P-JNK and Cleaved caspase-3 increased.Compared with IR,the ratio of TXB2/6-keto-PGF1αdecreased at each time point in IR+C (P<0.05),and the apoptosis rates decreased (t=3.34~6.38,P< 0.05).The protein expression of Cox-2,P-JNK and Cleaved caspase-3 decreased.Conclusions Celecoxib may help to protect HBMECs from releasing TXA2 and decreasing the ratio of TXB2/6-keto-PGF1α,and inhibitting apoptosis after irradiation.The mechanisms of apoptosis inhibition may be related to the inhibition of Cox-2 and P-JNK,caspase-3 Cleaved proteinexpressions.

Effects of Icariin on Partial Vasoactive Substances in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model / 医药导报

Objective To investigate the effects of icariin (ICA) on partial vasoactive substances in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model.Methods Sixty male SD rats were randomly divided into five groups:normal control group,model control group,ICA low-,middle-and high-dose (20,40,80 mg · kg-1 · d-1) group,12 rats in each group.Except for normal control group,the rats were injected with MCT (50 mg · kg-1 · d-1) to establish PAH model.After 1 week MCT-injection,ICA was given by intragastric administration for 3 weeks according to different groups.Mean pulmonary artery pressure (mPAP) was recorded through catheter connected with Power Lab system.Except for normal control group,the right ventricular hypertrophy index (RVHI) was calculated using formula:right ventricle weight/the weight of left ventricle with septum× 100％.The morphology of lung artery was assessed by HE staining.Concentration of angiotensin Ⅱ (Ang Ⅱ),endothelin (ET),prostaglandine F2α(PGF2α),thromboxane A2(TXA2) and prostacyclin (PGI2) in serum was measured by ELISA kit assay.The protein levels of angiotensin converting enzyme (ACE),cyclooxygenase-2 (COX-2) and thromboxane A2 synthetase (TXAS) were analyzed by Western blotting,expression of ACE,COX-2 and TXAS mRNA was measured by real time RT-PCR.Results Compared with the normal control group,mPAP [(48.5±5.2) mmHg] and RVHI (33.3±3.8)％in model control group were significantly increased (P ＜ 0.05),the morphology revealed there was obvious artery remodeling at distal artery,the contents of Ang Ⅱ,PGFA2,TXA2 in serum were elevated,and ACE,COX-2 and TXAS gene expression was up-regulated in rats treated with MCT.ICA (40,80 mg · kg-1 · d-1) treatment significantly attenuated mPAP,RVHI and pulmonary artery remodeling (P ＜ 0.05),and decreased the contents of serum Ang Ⅱ,ET,PGF2β,TXA2,and PGI2,and inhibited the gene expression of ACE,COX-2 and TXAS.Conclusion ICA decreases the contents of AngⅡ,ET,PGI2,PGF2α and TXA2 in the serum of MCT-induced PAH rats,which may be one of the mechanisms underlying ICA inhibiting PAH.

Effects of traditional Chinese medicine syndrome differentiation quadruple therapy on serum vascular active substance in patients with acute pancreatitis / 中国中西医结合急救杂志

Objective To observe the effects of traditional Chinese medicine (TCM) syndrome differentiation quadruple therapy on serum thromboxane A2 (TXA2), prostacyclin (PGI2) and platelet activating factor (PAF) levels in patients with acute pancreatitis (AP). Methods Ninety patients with AP admitted to the First Affiliated Hospital of Henan University of TCM from January 2016 to March 2017, and they were divided into an observation group and a control group according to the random numbers generated by computer inpatients, 45 cases in each group. The control group was given routine treatment of western medicine, and the observation group was given TCM syndrome differentiation quadruple therapy according to the patient's disease individual situation and on the basis of western medicine treatment. The TCM syndrome differentiation quadruple therapy included the following methods: intragastric administration of TCM decoction [gastrointestinal excess heat syndrome (rhubarb, sodium sulfate, aurantii fructus immaturus, magnolia bark, etc.), damp heat syndrome of liver and gallbladder (radix bupleuri, aurantii fructus immaturus, baical skullcap root, rhubarb, etc.), each group of above agents immersed in water and decocted to make juice 400 mL, once 100 mL taken orally, every 4 hours]; retention enema with TCM decoction [rhubarb, magnolia bark, aurantii fructus immaturus, sodium sulfate (dissolved) etc, each dose of agents forming decoction 400 mL, 200 mL taken for proctoclysis, once every 6 hours]; Chinese medicine package (boswellin, myrrha, dandelion, coptidis rhizoma and so on crushed and mixed with honey, then applied to the body surface of the pancreas and its periphery, 1 dose each time for 4 hours, once a day ); intravenous drip of blood-activating and stasis-resolving TCM (Dengzhanhuasu injection 100 mg added to 5% glucose solution 250 mL for intravenous drip). The times of disappearance of abdominal distension, abdominal pain, and the recovery times of bowel sound, blood amylase, lipase, C-reactive protein (CRP), white blood cell count (WBC) levels to normal were compared between the two groups; the modified CT severity index (MCTSI) score and the changes of serum TXA2, PAF and PGI2 levels were observed before and after treatment in the two groups. Results The abdominal pain and abdominal distension disappearance times in observation group were shorter than those in control group [abdominal pain (days): 5.07±1.88 vs. 6.02±1.89, abdominal distension (days): 3.50±1.49 vs. 4.40±1.53, both P < 0.05]; the recovery times of bowel sounds, WBC, CRP, amylase and lipase to normal were shorter than those of the control group [bowel sounds (days): 4.05±1.79 vs. 5.00±1.55, WBC (days): 3.93±1.49 vs. 5.98±2.90, CRP (days): 6.17±2.46 vs. 7.92±2.84, blood amylase (days): 3.5 (3.0, 5.0) vs. 5.0 (3.0, 5.5), lipase (days): 5.0 (3.0, 7.0) vs. 6.5 (5.0, 9.0), all P <0.05]; the scores of MCTSI in the two groups were lower than those before treatment and the degree of decrease in the observation group was more significant than that in the control group [2 (0, 4) vs. 4 (0, 6), P < 0.05]. The TXA2 and PAF levels of the two groups were significantly lower than those before treatment and the level of PGI2 was significantly higher than that before treatment; after treatment for 3 days, the differences between the two groups showed statistical significance and on the 7th day after treatment, the degrees of improvement in observation group were more obvious than those of the control group [TXA2 (ng/L): 276.81±31.48 vs. 345.42±47.27, PAF (ng/L): 72.65±17.61 vs. 89.77±15.59, PGI2 (ng/L): 104.43±18.67 vs. 94.37±17.91, all P < 0.05]; on the 14th day after treatment, the values of the two groups were very close and there were no statistically significant differences (all P >0.05). Conclusions The TCM differentiation syndrome quadruple therapy for treatment of AP is beneficial to the disappearance of clinical symptoms of patients with different syndromes, recovery of abnormal signs and improvement of laboratory indexes, and its early use can significantly reduce the serum levels of TXA2, PAF and increase the level of PGI2 in patients with AP.

Correlation between prostacyclin synthase gene rs5602 polymorphism and ischemia stroke in Chinese Han population / 国际脑血管病杂志

Objective To investigate the correlation between prostacyclin synthase (prostaglandin I2 synthase, PGIS) gene rs5602 single nucleotide polymorphism and ischemia stroke in Chinese Han population. Methods The patients with ischemia stroke and healthy controls in Chinese Han population were enroled. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) was used to detect the rs5602 polymorphism. Results A total of 297 patients with ischemic stroke (male 177 and female 120) and 291 healthy controls (male 165, female 126) over the same period were enroled. The frequencies of TT genotype (31. 1% vs. 43. 6% ; χ2 = 5. 773, P = 0. 016) and T alele (56. 8% vs. 65. 8% ; χ2 = 5. 793, P = 0. 016) in the male patients with ischemic stroke were significantly lower than those in the male healthy controls. Multivariate logistic regression analysis showed that the rs5602 TT genotype was a protective factor for ischemic stroke in male (odds ratio 0. 260, 95% confidence interval 0. 118-0. 570; P = 0. 001). Conclusions PGIS gene rs5602 polymorphism is associated with ischemic stroke in male in Chinese Han population.

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)

Role of Endothelium-Dependent Hyperpolarisation and Prostacyclin in Diabetes

The endothelium plays a crucial role in maintaining vascular homeostasis by producing several vasodilating factors, including nitric oxide (NO), prostacyclin (PGI2), and endothelium-dependent hyperpolarisation (EDH); however, the balance between endothelial relaxing and contracting factors is disrupted in disease states such as diabetes mellitus and hypertension. Most reported studies of endothelial dysfunction in diabetes focused on the actions of NO; however, there is accumulating evidence demonstrating that in addition to NO, PGI2 and EDH are likely to contribute to the vasodilatation of blood vessels. EDH plays an important role as a regulator of vascular tone and reactivity in resistance and conduit arteries of animal models and humans. PGI2 only plays a minimal role in endothelium-dependent vasodilatation but may serve as an important compensatory mechanism in conditions in which NO and EDH activities are decreased. Further studies are needed to determine the exact roles of EDH and PGI2 in the development of endothelial dysfunction and clinical vasculopathy in humans with type 1 and type 2 diabetes.

Effect of interleukin-1 on contractile function of rat thoracic aorta / 中华麻醉学杂志

Objective To investigate the effect of interleukin-1 (IL-1) on contractile function of rat thoracic aorta.Methods Forty male Sprague-Dawley rats,weighing 250-300 g,were sacrificed to obtain the thoracic aortic rings.The experiment was performed in 2 parts.Part Ⅰ The thoracic aortic rings were divided into 2 segments and randomly divided into 2 groups (n =20 each):control group and IL-1 group.In IL-1 group,the thoracic aortic rings were incubated with Kreb solution containing 20 ng/ml IL-1 for 2 h,and contracted with cumulative concentrations of phenylephrine,ranging from 10-9 to 10-5mol/L.In control group,the thoracic aortic rings were incubated with Kreb solution for 2 h,and contracted with cumulative concentrations of phenylephrine,ranging from 10 9 to 10-5mol/L.Part Ⅱ The thoracic aortic rings were divided into 3 segments and randomly divided into 3 groups (n=20 each):IL-1 group,IL-1+ L-NAME (the NOS inhibitor) group and IL-1 +cyclooxygenase inhibitor indomethacin group (IL-1 +Ⅰgroup).The thoracic aortic rings were incubated with Kreb solution containing 20 ng/ml IL-1 for 1.5 h in the three groups.In addition,in IL-1 +L-NAME and IL-1 +Ⅰ groups,the thoracic aortic rings were incubated for 30 min with Kreb solution containing 100 μmol/L L-NAME and 2.5 mmol/L indomethacin,respectively.Contraction of the thoracic aorta was then induced with cumulative concentrations of phenylephrine,ranging from 10 9 to 10-5 mol/L.In group IL-1,the thoracic aortic rings were incubated with Kreb solution.The maximum contractile tension of the thoracic aortic rings was recorded at each concentration of phenylephrine,and the percentage of the maximum contractile tension at the concentration of 10-6 mol/L in group C was obtained.Results Part Ⅰ The percentage of contractile tension at phenylephrine 10-s,10-7,l0 6 and 10-5mol/L was significantly decreased in IL-1 group as compared with C group.Part Ⅱ The percentage of contractile tension at phenylephrine 10-7,10-6 and 10-5mol/L was significantly increased in IL-1+L-NAME and IL-1+I groups as compared with IL-1 group.Conclusion IL-1 can inhibit the contraction of rat thoracic aorta,and promoted production of NO and prostacyclin may be involved in the mechanism.

Recent Advances in the Management of Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease characterized by pulmonary vascular remodeling that leads to increased pulmonary vascular resistance and pulmonary arterial pressure, most often resulting in right-sided heart failure. Originally considered to be a disorder of vasoconstriction and vasodilatation, it has become clear that the predominant characteristic of PAH is abnormal cellular proliferation leading to progressive obliteration of the pulmonary vasculature. Current PAH-specific therapies target one of three major pathways involved in development and progression of PAH: 1) The endothelin pathway targeted by the endothelin receptor antagonists (ERAs); 2) the prostacyclin pathway, targeted by prostacyclin analogs and 3) the nitric oxide (NO) pathway, targeted by the phosphodiesterase type 5 (PDE-5) inhibitors.

Effects of beraprost sodium on cerebral cortical neuron injury induced by chronic aluminum-overload in rats / 中国药理学通报

Aim To investigate the protective effects of beraprost sodium on cerebral cortical neuron injury in chronic aluminum-overload rats and its effects on PGIS-IP signaling pathway. Methods 75 SD rats were randomized into five groups: normal control group, chronic aluminum-overload group ( model group) and beraprost sodium groups-low dose (6 μg· kg-1 ), medium dose ( 12 μg · kg-1 ) and high dose (24 μg·kg-1). Aluminum gluconate (Al3+ 200 mg ·kg-1 d-1, once a day, 5d a week, for 20 weeks, p. o. ) was administered to rats of cerebral damage model. The rats of experimental groups were concomi-tantly treated with beraprost sodium ( p. o. ) daily for 20 weeks. After the model was built successfully, the spatial learning and memory( SLM) function was done by Morris water maze. The cortical neurons damage was detected by HE staining, SOD activities and MDA contents. The 6-k-PGF1α levels in cortex were meas-ured by ELISA. The expressions of PGIS, IP mRNA and IP protein were also studied. Results Compared with the rats of normal control group, the SLM function was significantly impaired ( P<0. 01 ) and considera-ble karyopycnosis was observed in model group rats. The SOD activities were weakened ( P <0. 01 ), the MDA contents increased ( P<0. 05 ) and the levels of 6-k-PGF1α raised significantly ( P <0. 01). The ex-pressions of PGIS and IP mRNA in the rats cortex obvi-ously increased ( P<0. 01 ), so did the expression of IP protein(P<0. 05). Compared with the rats of mod-el group, the SLM function of rats in experimental groups decreased significantly ( P<0. 01 ) and damage of cortical neurons reduced remarkably. The SOD ac-tivities increased ( P <0. 01 ) and the MDA contents decreased ( P <0. 01). Besides, the content of 6-k-PGF1α, the expressions of PGIS mRNA and IP protein in the rats cortex decreased significantly ( P<0. 05 ) as well as IP mRNA ( P<0. 01). Conclusion Our re-sults demonstrate that in cerebral cortical neuron of chronic aluminum-overload rats, beraprost sodium has notably protective effects and the mechanism might be related to PGIS-IP signaling pathway.

COX2-PGI2/TXA2 signal pathway involved in protective mechanism of PDTC pretreatment against global cerebral ischemia reperfusion rat hippocampus injury / 中国药理学通报

Aim To investigate the effects and mecha-nism of nuclear factor-κ B inhibitor, PDTC, on global cerebral ischemia reperfusion ( GCIR ) rat hippocam-pus. Methods Forty-eight adult male Sprague-Daw-ley rats were randomly divided into one control group receiving sham operation and three experimental groups all receiving global cerebral ischemia for 20 min. In PDTC 100 mg·kg-1 group ( P100 ) and PDTC 200 mg ·kg-1 group ( P200 ) , PDTC 100 mg · kg-1 or PDTC 200 mg·kg-1 was injected ip one hour before ischemi-a respectively. Spatial learning and memory function of rats were tested using Morris water maze. HE staining was employed to observe pathological changes of hipp-ocampal neurons. Expression of COX2 was measured by Western blot, and the content of PGI2 and TXA2 in rat hippocampus was detected by enzyme-linked immu-nosorbent assay. Results A significant increase of es-cape latency was observed in GCIR group compared to the sham operation group(P<0.05). PDTC 100 mg· kg-1 and PDTC 200 mg · kg-1 significantly reduced escape latency ( P <0.05 ) and histopathological injury in CA1 region of hippocampus. PDTC 100 mg · kg-1 and PDTC 200 mg · kg-1 also reduced COX2 expres-sion, PGI2 content, TXA2 content and PGI2/TXA2 . Conclusion Pretreatment with PDTC can protect hip-pocampus from GCIR injury through inhibition of COX2 expression and PGI2/TXA2 .

Effectiveness and Safety of Intravenous Iloprost for Severe Persistent Pulmonary Hypertension of the Newborn.

Objective: The aims of this study were to determine the effectiveness (oxygenation), safety (hemodynamic status) and short term outcomes of intravenous iloprost (IVI) administration as a rescue therapy in severe persistent pulmonary hypertension of the newborn (PPHN). Design: Retrospective medical records review. Setting: Tertiary neonatal intensive care unit at Songklanagarind Hospital, Songkhla Province, Hat Yai, Thailand. Participants: Newborns who received IVI as an adjunctive therapy for treatment of severe PPHN, as defined by an oxygen index (OI) of >20 and without response to conventional therapies. Main Outcome Measures: The change of OI and alveolar-arterial oxygen difference before and after commencement of IVI. Results: 33 neonates with severe PPHN at a median gestation of 39 weeks and a baseline OI of 40 (range, 21-101) received IVI. The median OI and alveolar-arterial oxygen difference had a statistically significant decrease after 2 hours of treatment and continued to decline thereafter (P<0.05). All infants received one or more inotropic medications and volume expanders to provide blood pressure support with no statistically significant difference of blood pressure and heart rate before and after IVI treatment. The mortality rate was 15.2%, all of them had initially severe hypoxemia with a median OI of 53.6. Conclusions: IVI may be effective in improving oxygenation and should be considered as a rescue therapy for infants with severe PPHN, especially in a limited resource environment with no inhaled nitric oxide available. Systemic hypotension may be a cause for concern.

Cotinine Overcome the Decrease of Prostacyclin Formation Induced by Nicotine after Sympathetic Stimulation in Microsomes from Isolated Rabbit Heart.

We studied the effects of cotinine, the major metabolite of nicotine, on nicotine-induced decrease in prostacyclin (PGI2) synthase activity of microsomes from isolated rabbit heart after sympathetic stimulation. Rabbit hearts were isolated along with their sympathetic nerves and perfused in accordance to the Langendorff method. Hearts were randomly divided into 10 groups treated with cotinine, either during sympathetic stimulation or prior to nicotine administration. PGI2 formation in cardiac microsomes was assessed by radioimmunoassay. The results showed that sympathetic stimulation increased PGI2 synthase activity of heart microsomes by 32 %. Nicotine dose dependently decreased PGI2 while cotinine increased it. In addition, perfused before nicotine, cotinine prevented the PGI2 decreasing effect of nicotine. The results suggest that pre-treatment with cotinine can be involved in the modulation of nicotine effects on PGI2 in hearts subjected to sympathetic stimulation.

Effects of a static magnetic field on proliferation, apoptosis and secretion in human umbilical cord endothelial cells / 中华物理医学与康复杂志

Objective To evaluate the effects of static magnetic fields (SMFs) of different intensity and exposure duration on the proliferation and apoptosis of human umbilical cord endothelial cells (HUVECs),and their release of nitric oxide (NO),6-keto-prostacyclin 1α (6-keto-PGF1α) and endothelin (ET-1).Methods Cultured HUVECs were exposed to a SMF at 5,22,86 or 135 mT for 8,12 or 24 hours.Their proliferation and apoptosis were monitored by flow cytometry (FCM).The medium was collected to test its NO content by optical density.ET-1 and 6-keto-PGF1α were measured by radioimmunization.Results ( 1 ) The proliferation of HUVECs increased when the cells were exposed to a SMF at 5 mT for 8 h,but a SMF at 135 mT for 12 h or 24 h inhibited the proliferation of HUVECs.(2)An SMF had no effect on apoptosis of HUVECs.(3)An SMF at 5 mT for 8 h increased the release of NO and 6-keto-PGF1 a,but the release of NO and 6-keto-PGF1 a decreased when the SMF intensity was 135 mT or the cells were exposed to an SMF for 12 h or 24 h.(4) An SMF at 5 mT or 22 mT for 8 h did not effect the release of ET-1.An SMF at 86 mT or 135 mT increased the release of ET-1.Compared with a control group,an SMF at 5 mT for 12 or 24 h did not affect the release of ET1,but at 22,80 or 135 mT,the release of ET-1 decreased significantly.Conclusions Exposure to a low intensity SMF for a short duration could improve the proliferation of HUVECs and increase the release of vasoactive factors,but if HUVECs are exposed to a strong SMF or exposed for a long duration,the proliferation and the release of vasoactive factors is decreased.