Diet Rich in Saturated Fat Decreases the Ratio of Thromboxane/prostacyclin in Healthy Men

Objective To investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane 62 (TXB2) and 6-keto prostaglandin F la (PGF la) in 27 healthy free-living male subjects aged 30 to 55 years. Methods It was a randomized crossover design. Each volunteer was randomly assigned to one of the two diets (high fat and low fat) for a period of 4 weeks, after which each subject resumed his usual diet for 2 weeks as a 'wash-out period', before being assigned to the other diet for an additional 4 weeks. Results Serum proportion of 20:4n-6 was 5% lower in the high fat (6.2% of total fatty acid) than in the low fat diet (6.5% of total fatty acid), which was associated with a significantly decreased ratio of the urinary excretion 11-dehydro TXB2 to 6-keto PGF lα (P<0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2. Conclusions Diet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

Effects of thromboxane and prostacyclin imbalance on hemodynamics and hemorrheology in severely burn patients

Fifty-seven bum patients were dosdy observed for 28 d postburn.In general,plasma levelof thromboxane B2（TXB2）,6-keto-PGFlx and TXB2/6-keto-PGFlx ratio all rose up abruptly tothe peak in the first half day after burns and then declined gradually.However the patterns of theirchanges were different:6-keto-PGFlx returned to the control level in the 2nd day postburn,remained in a higher level than the control even in the 5th day postburn,and the increase ofTXB2/6-keto-PGFlα ratio was especially pronounced in the first 3 d postbum.It was also shownthat the changes of hemodynamics and hemorrheology occurred simultaneously with the imbalanceof thromboxane and prcstacyclin in the early postburn stage.The extent of the imbalance accordedwith the severity of hemodynamical and hemorrheological changes and was closely correlated withthe changes with the stroke volume,cardiac output,systemic vascular resistance,circulatory plateletaggregate ratio,platelet count and blood vinery.These findings suggest that the imbalance be-tween thromboxane and prostacyclin plays an important role in the changes of hemodynamics andhemorrheology in severe burn cases.

RELATION OF MALIGNANT TUMOR TO PROSTACYCLIN AND THROMBOXANE

The level of 6-keto-PGF1αand thromboxane B2(TXB2) in Plasma was determined with radioimmunoassay in 58 normal subjects and 92 Patients with various cancers(including lung,hepatic,gastric,esophageal and pancreatic carcinoma).The results showed that 6-keto-PGF1α.In plasma was 10.21±2.75 Pg/ml,and TXB2 146.03±37.31 Pg/ml in normal individuals,the ratio of 6-keto-PGF1α to TXB2 was 0.07;while in cancer Patients 6-keto-PGF1αwas 27.5±16.9 Pg/ml and TXB2 315.4±173.4 Pg/ml, the ratio of 6-keto-PGF1αto TXB2 was 0.08.The values of 6-keto-PGF1αand TXB2 in plasma of cancer patients were 2.69 folds and 2.16 folds higher than that of the two groups,respectively.The difference between the two groups was statistically significant(P<0.01).It indicates that the synthesis and release of PGI2 and TXA2 of cancer tissues increases greatly as compared to the normals.The study also revealed that the size of tumor,metastasis and histological classification had no obvious relation to PGs.

Effect of Intra-arachnoid Space Perfusion on Thromboxane A and Prostacycline in Experimental Spinal Cord Injury

In order to understand the relation between TXA2- PGI2 and secondary trauma and the effect of intra-arachnoid perfusion of dexamethasone and verapamil on alteration of TXA,-PGI, following spinal cord injury, TXB2 and 6-keto-PGFconcentration and pathological changes in injured site 1, 2, 4 and 6 h after injury were studied using a rabbit spinal cord injury model by Allen's weight drop method.

Changes of thromboxane and prostacyclin in the pathogenesis of multiple organ failure in severe burns

Fifty-seven severely burned patients were divided into 2 groups:16 withmultiple organ failure（MOF）,and 41 without MOF.It was found that the levelof thromboxane B2（TXB2）and the ratio between TXB2 and 6-keto-prostaglandinF1α(TBX2/6-keto-PGF1α)in plasma and in visceral tissues were increased and re-mained significantly high in the first 5～7 d postburn in patients with MOF but notso in those without MOF.The circulatory platelet aggregate ratio（CPAR）wasmarkedly decreased in the same period in MOF group.Myocardial enzymes（CPK,LDH,and GOT）were markedly increased in the first 3d and remainedsignificantly high within 7 d postburn.Degeneration,structural destruction,edema,hemorrhage and thrombosis were revealed in cardiac,pulmonary,renal andhepatic tissues succumbing to functional failure.Thirteen out of the 16 cases de-veloped MOF during the 3rd to 7th day posthurn and 11 died in that period.These findings substantiate that persistent increase of thromboxane andthromboxane/prostacyclin ratio is closely related to the origin and development ofMOF after burn injury.

Neuroprotective Effect of a Prostacyclin Agonist (ONO-1301) with Thromboxane Synthase Inhibitory Activity in Rats Subjected to Cerebral Ischemia

ONO-1301 has been developed as a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. In the present study, we investigated the cerebroprotective effect of ONO-1301 on post-ischemic injury induced by cerebral ischemia in rats. ONO-1301 (1 and 10 mg/kg) was administrated orally at reperfusion and then twice a day for 42 days. The cell damage induced by cerebral ischemia in the hippocampal CA1 was evaluated using both Nissl staining and proliferating cell nuclear antigen (PCNA) staining on the 42 days after cerebral ischemia. Activated astrocytes were evaluated using immunofluorescence staining with GFAP on the 42 days after cerebral ischemia. Spatial learning was assessed using a Morris water maze (MWM) task on the 56 days (i.e. after a 14 days washout period). ONO-1301- treated rats (1 and 10 mg/kg) significantly improved cell death in the hippocampal CA1, the number of PCNA-positive cells and astrocyte activation. The spatial learning of ONO-1301-treated rats compared with vehicle- treated rats in the MWM task. These results suggest that repeated treatment with oral ONO-1301 could prevent or limit post-ischemic brain damage. In particular, treatment with ONO-1301 within 7 days after ischemia is most effective to improve ischemic damage.

Platelet thromboxane(11-dehydro-Thromboxane B_2) and aspirin response in patients with diabetes and coronary artery disease

Aspirin(ASA) irreversibly inhibits platelet cyclooxygenase-1(COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes(DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2(11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls(P = 0.024): female subjects(DM and controls) had 50.9% higher baseline 11dhTxB2 than males(P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM(71.7%) and controls(75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders(ASA "resistant") in DM than in controls(14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome(ACS) patients was 28.6 and 28.7%, in spite of a significant(81.6%) inhibition of urinary 11dhTxB2(P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.

Associations between thromboxane A synthase 1 gene polymorphisms and the risk of ischemic stroke in a Chinese Han population

Thromboxane A synthase 1 （TBXAS1） catalyses the synthesis of thromboxane A2 （TXA2）, which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls （P 〈 0.01 and P = 0.02）. Furthermore, compared with the GG ＋ GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke （odds ratio （OR） = 1.80, 95% confidence interval （CI）： 1.16–2.79, P 〈 0.01）. Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke （OR = 1.94,95% CI ： 1.13–3.33, P = 0.02）. The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis （OR = 1.49, 95% CI： 1.10–2.00, P 〈 0.01）. These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry （registration number： ChiCTR-COC-17013559）.

Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in cirrhotic patients undergoing liver transplantation

AIM： To investigate the perioperative changes of nitric oxide （NO） and endothelin （ET）, thromboxane A2 （TXA2） and prostaglandin （PGI2） during liver transplantation in end-stage liver disease patients. METHODS： Twenty-seven patients with end-stage cirrhosis undergoing liver transplantation were enrolled in this prospective study. Blood samples were obtained from superior vena at five different surgical stages. Plasma concentrations of nitrate and nitrite were determined to reflect plasma NO levels. Plasma levels of ET-1, 6-keto-PGF1 alpha and thromboxane B2 （TXB2）, the latter two being stable metabolites of PGI2 and TXA2 respectively, were measured.RESULTS： The NO level decreased significantly after vascular cross-clamping and increased significantly at 30 rain after reperfusion. While the ET levels at 30 rain after clamping and after reperfusion were significantly elevated. The ratio of NO/ET decreased significantly at 30 rain after vascular cross-clamping and at the end of surgery. The PGI2 level and the TXA2 during liver transplantation were significantly higher than the baseline level, but the ratio of TXA2/PGI2 decreased significantly at 30 rain after clamping. CONCLUSION： NO/ET and TXA2/PGI2 change during liver transplantation. Although the precise mechanism remains unknown, they may play a role in the pathobiology of a variety of liver transplant-relevant processes.

Antithrombotic Effects of BM-13505,a ThromboxaneReceptor Antagonist

BM-13 505 is a new type of thromboxane receptor antagonist developed firstabfoad and synthesized in our school.wita modife method recently。The resultS of our study showed that the occlusion time of carotid artery in experimental thrombosis rats was prolonged by BM-13505,0.45 and 0.23 mglkg iv fP<0.00 1 and <0.01 respectively).B·13505 2 mgjkg iv ef fectively prevented the cerebral thrombosis caused by AA 4 mg/kg in rats(P<0.01) BM-13505 10 mg/kg ip prevented the AA-induced pulmonary thrombosis in mice(P<0.01).Tail bleeding time of mice was prolonged by this dru.BM-13505 significantly inhibited the AA-induced rabbit platelet aggregation,with an IC￣(50) of0.17 μmol/L; ADp-and collagen-induced aggregations were not affected.TXB_2 level in platelets and that in mice plasma were decreased by BM-13505,but cAMP level inplatelets was not affected. BM-13505 may be possibly developed into a useful anti-platelet and anti-thromboti c drug。

Inhibition of Cyclooxygenase and Thromboxane Synthetase on Oxygen Delivery and Utilization in Acute Respiratory Failure Canine

The puapose of this study was to evaluate the effects of cyclooxygenase inhibitor (Ibuprofen)and thromboxane synthetase inhibitor (OKY-046) on oxygen metabolism in acute respiratory failure.Intratracheal instillation of hydrochloric acid was produced in 18 dogs, six dogs were pretreated with ibuprofen (IBU), six dogs with OKY-046 (OKY),and the remaindere used as control (CTR). After acid aspiration oxygen delivery (DO_2) fell in all groups as a results of decreased PaO_2 and cardiac output.However, oxygen consumption (VO_2)was maintained in all animals by the end of experiments except in CTR group. Arterial oxygen content maintained at baseline level throughout the experiments in IBU group. Meanwhile a significantly decreased mixed venous oxygen tension was found in OKY group after acid challenge. Liner regression of _vO_2 and DO_2 was confirmed in both CTR and OKY group. However,the dependent relationship between VO_2 and DO_2 was not identified in IBU group, which may indicate that the body oxygen metabolism was maintained rather well in acute rcspiratory failure dogs treated with ibuproten.

Effects of procainamide on adenosine diphosphate-induced platelet aggregation and thromboxane B_2 production in rabbits in vitro

Turbidimetry and radioimmunoassay were used to study the effects of procainamide (PA ) onadenosine diphosphate (ADP)-induced rabbit platelet aggregation and thromboxane B2 (TXB2) production invitro. PA 8. 5--544. 0 μmol L-1 inhibited ADP-induced platelet aggregation and TXB2 production, and theinhibition rates were 26. 7% -- 66. 7 % and 21. 4 % -- 70. 1 %, respectively. There was positive correlation between PA concentration and its efficiency in inhibiting the platelet aggregation and TXB2 production, and alsobetween the inhibition rates of platelet aggregation and that of TXB2 production. The three linear equationsand main parameters were The results indicate that PA could significantly inhibit ADP--induced platelet aggregation and TXB2 production in rabbits.

血清NO、TXB2、ET-1水平与慢性心力衰竭患者NYHA心功能分级、心功能指标的关系及对其预后的预测价值

目的 分析血清一氧化氮(NO)、血栓素B2(TXB2)、内皮素-1(ET-1)水平与慢性心力衰竭(CHF)患者美国纽约心脏病协会(NYHA)心功能分级、心功能指标的关系及对其预后的预测价值。方法 选取2020年8月至2022年8月在该院住院的108例CHF患者作为研究对象,根据NYHA心功能分级标准将患者分为NYHAⅡ级组、NYHAⅢ级组和NYHAⅣ级组。随访1年,根据随访期间患者是否发生严重心律失常、心肌梗死、死亡等不良事件将患者分为预后不良组和预后良好组。采用Pearson相关分析预后不良组CHF患者血清NO、TXB2、ET-1水平与心功能指标的相关性。采用Spearman相关分析CHF患者血清NO、TXB2、ET-1水平与NYHA心功能分级的相关性。采用多因素Logistic回归分析CHF患者预后不良的影响因素。绘制受试者工作特征(ROC)曲线分析血清NO、TXB2、ET-1单独及联合检测对CHF患者预后不良的预测价值。结果 NYHAⅡ级组、Ⅲ级组、Ⅳ级组分别有28、41、39例患者。NYHAⅣ级组CHF患者血清NO水平低于NYHAⅡ级组、NYHAⅢ级组,血清TXB2、ET-1水平高于NYHAⅡ级组、NYHAⅢ级组,且NYHAⅢ级组血清NO水平低于NYHAⅡ级组,血清TXB2、ET-1水平高于NYHAⅡ级组,差异均有统计学意义(P<0.05)。随访期间发生14例严重心律失常、18例心肌梗死、7例死亡。预后不良组和预后良好组分别有39、69例患者。预后不良组左心室舒张末内径(LVEDD)及血清TXB2、ET-1水平均高于预后良好组,左心室射血分数(LVEF)及血清NO水平均低于预后良好组,差异均有统计学意义(P<0.05)。Spearman相关分析结果显示,CHF患者血清NO水平与NYHA心功能分级呈负相关(P<0.05),血清TXB2、ET-1水平与NYHA心功能分级呈正相关(P<0.05)。Pearson相关分析结果显示,预后不良组CHF患者LVEF与血清NO水平呈正相关(P<0.05),与血清TXB2、ET-1水平呈负相关(P<0.05)。预后不良组CHF患者LVEDD与血清NO水平呈负相关,与血清TXB2、ET-1水平呈正相关(P<0.05)。多因素Logistic回归分析结果显示,NO>51.02μmol/L是CHF患者预后不良的保护因素(P<0.05),TXB2>130.94 ng/L、ET-1>57.43 ng/L是CHF患者预后不良的危险因素(P<0.05)。ROC曲线分析结果显示,血清NO、TXB2、ET-1单独及3项指标联合预测CHF患者预后不良的曲线下面积(AUC)分别为0.858、0.841、0.816、0.963。3项指标联合预测的AUC高于NO、TXB2、ET-1单独预测的AUC(Z=2.579、2.638、3.312,P<0.05)。结论 血清NO、TXB2、ET-1水平与CHF患者NYHA心功能分级、心功能指标有关,可有效预测CHF患者预后不良。

Prostacyclin decreases splanchnic vascular contractility in cirrhotic rats

BACKGROUND： Prostacyclin has been shown to increase portal hypertension, but the mechanism is unclear. This study aimed to investigate whether the overproduction of prostacyclin（PGI2） in cirrhosis participates in the splanchnic vascular hyporesponsiveness to vasoconstrictors in cirrhotic rats.METHODS： Cirrhotic model was created by subcutaneous injection of 60% carbon tetrachloride（CCl4） corn oil solution combined with intermittent drinking of 5% alcohol, and agematched rats served as controls. The isolated third-generation mesenteric arterioles were used to examine the contractile response to norepinephrine. The changes in vascular diameter were observed under a microscope imaging device. The plasma concentration of 6-ketone-prostaglandin F1α（6-keto-PGF1α, a stable metabolite of PGI2） was tested via enzyme immunoassays and the expression of cyclooxygenase（COX） in mesenteric arteries was detected by Western blotting.RESULTS： In parallel with the increase of plasma 6-ketoPGF1α, the contractile response of arterioles from cirrhotic rats to norepinephrine was significantly impaired compared with that from controls. Inhibition of PGI2 or protein kinase A with indomethacin or Rp-adenosine 3＇, 5＇-cyclic monophosphothioate（Rp-cAMPS） partially reversed the vascular hypo-contractile response to norepinephrine in arterioles from cirrhotic rats.Indomethacin significantly decreased the plasma 6-keto-PGF1α.Furthermore, indomethacin significantly attenuated the effect of Rp-cAMPS on arterioles from cirrhotic rats. COX-1 expression was up-regulated in mesenteric arteries from cirrhotic rats,whereas COX-2 was not detectable in the mesenteric arteries from both cirrhotic and control rats.CONCLUSION： Enhanced COX-1 expression in cirrhotic rats resulted in elevated PGI2 production which partially contributedto the splanchnic vascular hyporesponsiveness to a vasoconstrictor via the protein kinase A pathway.

Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg·d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg·d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α (TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438±102 vs 841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNPa (indomethacin vs N/S: 22±5 vs 10±1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure.

Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome

AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome(ARDS).METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of i NO(20 ppm) or nebulized epoprostenol(10 μg/mL) was done in all patients. Thereafter, inhaled milrinone(1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide(iN O) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen(PaO_2) were recorded before and after each inhaled therapyadministration.RESULTS The majority of ARDS were of pulmonary cause(n = 13) and pneumonia(n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass(n = 2), smoke inhalation injury(n = 1), thoracic trauma and pulmonary contusions(n = 2) and aspiration(n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and i NO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO 2 from baseline was 8.8 mmH g [interquartile range(IQR) = 16.3], 6.0 mm Hg(IQR = 18.4), 6 mm Hg(IQR = 15.8) and 9.2 mm Hg(IQR = 20.2) respectively with i NO, epoprostenol, inhaled milrinone, and i NO added to milrinone. Only i NO and the combination of inhaled milrinone and i NO had a statistically significant effect on PaO 2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.

Ligustrizini promotes prostacyclin release from cultured human umbilical cord vein endothelial cells

The endothelial cells derived from human umbilical cord vein were treated with 200 μg/ml ligustrizini. The inhibrtory rate of platelet aggregation of the supernatant from the cultured endothelial cells treated with ligustrizini was 91% and that of superna

EFFECTS OF MODULATED LDLs ON THE RELEASE OF ENDOTHELIN-1 AND PROSTACYCLIN BY ENDOTHELIAL CELLS IN CULTURE

Objective To study the releases of endothelin-1 and prostacyclin by endothelial cells in culture and to elucidate how these releases were influenced by smoke-treated low density lipoprotein. Methods We exposed en- dothelial cell cultures to native or oxidized low density lipoproteins,low density lipoproteins treated by dimethylsul- foxide-soluble particles from cigarette smoke or dimethylsulfoxide alones. The release of endothelin-1 was assayed by bioassay and the release of prostacyclin was assayed by radioimmunoassay. Results Low density lipoproteins treated by smoke significantly increased the release or endothelin-1 (P<0.025) and decreased the release of prostacyclin (P< 0.02) by endothelial cells in culture, contrast to native or dimethylsulfoxide-treated lipoproteins. Conclusion The main part or vasoconstrictor activity in conditioned medium from bovine aortic EC is endothelin-1.

Effects of prostacyclin derivatives combined with valsartan therapy on the blood biochemical indexes in patients with early hypertensive nephropathy

Objective:To explore the effects of prostacyclin derivatives combined with valsartan therapy on the blood biochemical indexes in patients with early hypertensive nephropathy.Methods: A total of 110 patients with hypertensive nephropathy who were treated in the hospital between December 2014 and March 2017 were divided into control group (n=55) and experimental group (n=55) by random number table method. Control group received valsartan therapy, and experimental group received prostacyclin derivatives combined with valsartan therapy, which lasted for 20 weeks. The differences in the contents of renal function indexes, urinary protein indexes and endothelial injury markers were compared between the two groups before and after treatment.Results: Before treatment, the differences in the contents of renal function indexes, urinary protein indexes and endothelial injury markers were not statistically significant between the two groups. After 20 weeks of treatment, renal function indexes SCr, BUN, UA and CysC levels in peripheral blood of experimental group were lower than those of control group;urinary protein indexes ALB,β2-MG andα1-MG contents were lower than those of control group;endothelial injury markers ET-1 and E-selectin contents in peripheral blood were lower than those of control group whereas NO and CGRP contents were higher than those of control group.Conclusion: Prostacyclin derivatives combined with valsartan therapy can effectively optimize the renal function, reduce the urinary protein and alleviate the vascular endothelial injury in patients with early hypertensive nephropathy and improve the overall therapeutic effect.

Interaction of endothelin-1 and prostacyclin during pathological process in patients with ischemic cerebral infarction

Objective To investigate the interaction and c linical significance of changes in p lasma endothelin-1(ET-1)and prostacyclin(PGI 2 )concentrations in patients with isc hemic cerebral infarction.Methods Plasma ET-1and 6-keto-PGF 1 α(resistant metabolite of PGI 2 )concentrations were measured in 37p atients(study group)with ischemic cerebral infarction a nd 34healthy volunteers(control group)by ra-dioimmunoassay.Results Plasma ET-1concentrations in patie nts of study group were markedly higher than that of control group(P <0.01)and 6-keto-PGF 1 αconcentrations in patients of study group were significantly lower than that of control subjects(P <0.01).Plasma ET-1concentrations in control subjects were positively correlated with 6-k eto-PGF 1 αconcentrations and no correlation i n the study group.Conclusion Both ET-1and PGI 2 are participated in patho-physiolo gic process of ischemic cerebral inf arction.ET-1is a virulence factor a nd may play a deleterious role in ischemic cerebral infarction,PGI 2 is a conservancy factor and endogenetic antagonist of ET-1.It may provid e useful therapy parameter to find out ectogenesis PGI 2 or analog for treating the patients with ischemic cerebral infarction wi th reason.