OBJECTIVETo investigate the roles of thromboxane A(2) (TXA(2)) and prostaglandin I(2) (PGI(2)) in development of oligohydramnios.

METHODSThe concentration of TXB(2) and 6-keto-PGF1 in umbilical cord blood collected from 30 normal parturients (control) and 30 parturients with oligohydramnios was detected by radioimmunoassay to calculate the TXA(2)/PGI(2) ratio. Immunohistochemistry was performed to detect the contents of TXA(2)R in vascular endothelial cell in the placental villi.

RESULTSCompared with the control group, the concentration of umbilical cord blood TXB(2) in oligohydramnios group was significantly increased (P<0.01), but the elevation of 6-keto-PGF(2) concentration was not statistically significant (P>0.05). The oligohydramnios group showed significantly higher positivity rates of TXB2 and 6-keto-PGF1 in than the control group (P<0.01), and the positivity rate of TXA(2)R in the vascular endothelial cells in the placental villi was also significantly higher in the oligohydramnios group (22/30, 77.3% vs 11/30, 36.7%, P<0.05). Most of the TXA(2)R-positive cases in the oligohydramnios group showed strong positivities of TXA(2)R.

CONCLUSIONAbnormal elevation of TXA(2) concentration in the umbilical cord blood and the TXA(2)/PGI(2) imbalance are responsible for the development of oligohydramnios.

Adult ; Alprostadil ; analogs & derivatives ; blood ; Epoprostenol ; blood ; Female ; Fetal Blood ; chemistry ; Humans ; Oligohydramnios ; metabolism ; Placenta ; chemistry ; Pregnancy ; Radioimmunoassay ; Receptors, Thromboxane A2, Prostaglandin H2 ; chemistry ; Thromboxane A2 ; blood

In order to find out the relationship between arachidonic acid(AA) metabolites and the development of vasospasm following a subarachnoid hemorrhage(SAH), we evaluated the cerebrospinal fluid(CSF) levels of the two main AA metabolites, prostacyclin(PGI2) and thromboxane A2(TXAZ) by measuring their stable degredation products 6-keto-prostaglandin F1alpha(PGF1) and thromboxane B2(TXB2) using radioimmunoassay methods in 32 patients after an aneurysmal rupture and in 11 patients without an aneurysmal rupture as a control group. We compared the data between aneurysmal ruptured patients and control group patients. We also divided the data of the aneurysmal ruptured patients into 3 groups checking them between 1-4, 5-11, and 12-28 days after the SAH, and compared the data among the groups, then the data was also compared between non-vasospasm and clinical or severe angiographic vasospasm groups of patients. The results showed that the AA metabolism was enhanced after the SAH, The TXB2 increased the greatest amount in 1-4 days after the SAH and significantly decreased statistically 12 days after the SAH(p<0.002). This study also showed that the TXB2 level was significantly higher statistically in 1 to 4 days in the clinical or angiogrophically severe vasospasm group than in the non-vasospasm group of patients(p<0.032). PGF1 did not show any statistically significant changes according to the number of SAH days or a difference between the vasospasm and non-vasospasm groups. This result suggests if the AA metabolites are involved in the pathogenesis of cerebral vasospasm, and the lumbar CSF levels of AA metabolites in aneurysmal patients reflect the arterial synthesis of PGI2 and platelet origin of TXA2, the elevation of TXA2 or other vasoconstrictor prostaglandins is more likely to play a major role in the pathogenesis of vasospasm than PGI2 deficiency. The measurements of the CSF TXB2 in 1 to 4 days after a SAH may have an expectant value in the development of clinical or severe angiographic vasospasm(exclude the accompanying intraventricular hemorrhage patients).
Aneurysm* ; Arachidonic Acid ; Blood Platelets ; Cerebrospinal Fluid* ; Epoprostenol ; Hemorrhage ; Humans ; Metabolism ; Prostaglandins I ; Radioimmunoassay ; Rupture ; Subarachnoid Hemorrhage* ; Thromboxane A2 ; Thromboxane B2* ; Vasospasm, Intracranial

This study was designed to investigate inhibitory effects and possible mechanisms of snake venom tripeptide (pENW) on platelet adhesion in order to promote the development of a novel anti-platelet therapy. To study the inhibitory effects of pENW on platelet adhesion, washed platelets pre-incubated with pENW (116.5-466.2 μmol x L(-1)) were used to test the ability of platelet adhesion to fibrinogen. Effect of pENW on fibrin clot retraction was also tested. Effect of pENW on platelets viability was tested by MTT assay. Effect of pENW on reactive-oxygen species (ROS) levels of platelet was studied by flow cytometry assay. Calcium mobilization in Fura-2/AM-loaded platelets was monitored with a spectrofluorimeter. Cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), thromboxane A2 (determined as its metabolite thromboxane B2) were measured using enzyme immunoassay kits. Akt, ERK and p38 phosphorylation were tested by Western blot. The results showed that pENW inhibited platelet adhesion and fibrin clot retraction in a concentration-dependent manner without cytotoxicity. Intracellular cGMP and cAMP in both resting and thrombin-activated platelets were increased by pENW. In addition, pENW attenuated intracellular Ca2+ mobilization and TXA2 production in platelets stimulated by thrombin. As shown by Western blot assay, Akt, ERK and p38 phosphorylation in thrombin-induced platelet were attenuated by pENW. However, inhibitory effects of pENW had nothing to do with ROS. Thus, pENW exhibited a significant inhibition on platelet adhesion to fibrinogen, which means pENW could block the first step of thrombosis as while as retard the more stable clot formation. The mechanisms of pENW on inhibition platelet adhesion might be related to instant regulations, such as protein kinases.
Blood Platelets ; drug effects ; Blotting, Western ; Calcium ; metabolism ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Flow Cytometry ; Phosphorylation ; Platelet Aggregation ; drug effects ; Reactive Oxygen Species ; metabolism ; Snake Venoms ; chemistry ; Thromboxane A2 ; metabolism ; Thromboxane B2 ; metabolism

OBJECTIVETo observe the alteration of plasma levels of thromboxane A2 (TXA2) and prostacyclin (PGI2) as well as changes of microcirculation in renal cortex of obstructive jaundice model rats, and to study the effect of Radix Salviae miltiorrhizae (SM) on them.

METHODSSD rats were randomly divided into three groups: the sham operation group (A), the common bile duct ligation model group (B), and the SM treated model group (C). Their blood plasma TXA2/PGI2 ratio (T/P), blood levels of urea nitrogen (BUN) and creatinine (Cr) were determined respectively in batches (8 rats from each group) on the 3 rd, 7th and 10th day, their capillary caliber (CC) in renal cortex was measured at the same time points using WX-9 type microcirculation microscope.

RESULTSCompared with Group A, T/P was higher and CC was smaller in Group B at all the time points. Levels of BUN and Cr increased on day 7 and day 10 after modeling (P<0.05), and they were increasing markedly along with the elongation of the obstructive time (P<0.05). As compared with Group B, T/P was lower and CC was expanded in Group C, with levels of BUN and Cr lowered on day 10 (P<0.05).

CONCLUSIONT/P elevation and renal microcirculation obstacle are the important factors for inducing renal injury in obstructive jaundice, and SM shows a protective effect on kidney against the injury.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Epoprostenol ; blood ; Jaundice, Obstructive ; drug therapy ; metabolism ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry ; Thromboxane A2 ; blood

Prostanoid metabolites are key mediators in inflammatory responses, and accumulating evidence suggests that mesenchymal stem cells (MSCs) can be recruited to injured or inflamed tissues. In the present study, we investigated whether prostanoid metabolites can regulate migration, proliferation, and differentiation potentials of MSCs. We demonstrated herein that the stable thromboxane A2 (TxA2) mimetic U46619 strongly stimulated migration and proliferation of human adipose tissue-derived MSCs (hADSCs). Furthermore, U46619 treatment increased expression of alpha-smooth muscle actin (alpha-SMA), a smooth muscle marker, in hADSCs, suggesting differentiation of hADSCs into smooth muscle-like cells. U46619 activated ERK and p38 MAPK, and pretreatment of the cells with the MEK inhibitor U0126 or the p38 MAPK inhibitor SB202190 abrogated the U46619-induced migration, proliferation, and alpha-SMA expression. These results suggest that TxA2 plays a key role in the migration, proliferation, and differentiation of hADSCs into smooth muscle-like cells through signaling mechanisms involving ERK and p38 MAPK.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; Adipose Tissue/*cytology ; *Cell Physiological Processes/drug effects ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Mesenchymal Stem Cells/*cytology ; Receptors, Thromboxane A2, Prostaglandin H2/metabolism ; Signal Transduction ; Thromboxane A2/*metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism

OBJECTIVETo provide more detailed information on the roles of lipid peroxidation in the pathogenesis of chronic pancreatic injuries in a pre-clinical rat model.

METHODSTotally 72 rats were divided into 6 groups (12 in each group) Rats in 5 experimental groups (n = 12) were fed with a high-fat diet (1% cholesterol, 10% lard, 0.3% sodium tauroglycocholate, 87.3% standard rodent chow as the control group) for 2, 4, 6, 10 and 16 weeks, respectively. Morphological studies in the pancreas tissue samples from rats were investigated by using various histological methods. Pancreatic stellate cells (PSCs) were identified by immunohistochemical staining for Desmin and α-smooth muscle actin (α-SMA). The expression of the lipid peroxidation was detected by immunostaining for 4-hydroxy-2-nonenal (4-HNE) and thromboxane A2 receptor (TxA2r). The co-localization of α-SMA and 4-HNE or α-SMA and TxA2r in PSCs was also analyzed in this study.

RESULTSPancreatic cells with positive staining for Desmin and α-SMA in HFD rats were distributed in a more extensive way when compared to that in the control group. The levels of pancreatic 4-HNE and TxA2r were increased in rats from HFD groups significantly. The co-localization of 4-HNE and TxA2r were also found within activated PSCs in both of groups.

CONCLUSIONThe results showed that a chronic HFD feeding may increase the lipid peroxidation process and collagen synthesis through a critical signaling pathway of activated PSCs following pancreatic injuries in rats.

Actins ; metabolism ; Aldehydes ; metabolism ; Animals ; Collagen ; biosynthesis ; Desmin ; metabolism ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Lipid Peroxidation ; Male ; Oxidative Stress ; Pancreas ; metabolism ; pathology ; Pancreatic Diseases ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Receptors, Thromboxane A2, Prostaglandin H2 ; metabolism

AIMTo study the effect of aspirin on chronic hypoxia and hypercapnic pulmonary hypertension.

METHODSSD rats were randomly divided into normal control group (A), hypoxic hypercapnic group (B), hypoxic hypercapnia + aspirin group (C). The concentration of TXB2 and 6-keto-PGF1alpha in plasma and in lung were detected by the technique of radioimmunology.

RESULTS(1) mPAP was significantly higher in B group than those of A and C group. Differences of mCAP were not significant in three groups. (2) Light microscopy showed that WA/TA (vessel wall area/total area) and PAMT (the thickness of medial smooth cell layer) were significantly higher in B group than those of A and C group. (3) The concentration of TXB2 and 6-keto-PGF1alpha in plasma and lung as well as the ratio of TXB2/6-keto-PGF1alpha were significantly higher in rats of B group than those of A and C group.

CONCLUSIONAspirin may inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Aspirin ; pharmacology ; Carotid Arteries ; pathology ; physiopathology ; Epoprostenol ; metabolism ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; metabolism ; pathology ; physiopathology ; Hypoxia ; physiopathology ; Male ; Pulmonary Artery ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Thromboxane A2 ; metabolism

OBJECTIVETo investigate the effects of electro-acupuncture (EA) combined general anesthesia on myocardial injury of high blood sugar patients with coronary heart disease (CHD) in the perioperative phase.

METHODSRecruited were 40 senile patients with glycosylated hemoglobin (HbA1c) more than 6.5%. They were more than 60 years old. They received post-traumatic fracture reduction surgery of four limbs. They were randomly assigned to two groups, Group N (treated by general intravenous anesthesia) and Group D (treated by EA combined with general intravenous anesthesia), 20 in each group. All patients were maintained anesthesia by propofol, fentanyl, and vecuronium. Prior to the induction of anesthesia, patients in Group D received induction of EA at Neiguan (PC6) and Baihui (DU20) for 20 min, which lasted to the end of the surgery. At before intubation (T0), immediately after intubation (T1), 5 min (T2), immediately after extubation (T3), 5 min (T4), 60 min (T5), 180 min (T6), the fast blood glucose (FBG), plasma vasoactive substance TXB2 and 6-K-prostacycline (6-K-PGF1alpha) were detected in the two groups. The glucose coefficient of variation (GluCV) and the ratio of TXB2/6-K-PGF1alpha were calculated. The changes of ST-segment elevation (mV, sampling 1 min after each time point, and the mean calculated) was recorded.

RESULTSThere was no statistical difference in all the tested values between the two groups at T0 (P>0.05). The FBG, ST elevation, and the ratio of TXB2/6-K-PGF1alpha were significantly higher at each time point than at T0 in Group N (P<0.05), while there was no statistical difference in Group D (P>0.05). The ratio of TXB2/6-K-PGF1alpha and ST elevation were significantly higher in Group N than in Group D (P<0.01). The TXB2 and 6-K-PGF1alpha were significantly higher at each time point than at T0 in the two groups (P<0.05). The increment of TXB2 was obviously lower in Group D than in Group N (P<0.05), but the increment of 6-K-PGF1alpha was obviously higher in Group D than in Group N (P<0.05).

CONCLUSIONEA could reduce the perioperative stress response to the injury of coronary vascular endothelial cells, and improve myocardial ischemia and CHD patients' prognosis by regulating the central nervous system, the cardiovascular active substances, and anti-oxygen free radicals.

Acupuncture Analgesia ; Aged ; Anesthesia, General ; Blood Glucose ; analysis ; Coronary Disease ; metabolism ; surgery ; Electroacupuncture ; Epoprostenol ; metabolism ; Female ; Glycated Hemoglobin A ; analysis ; Humans ; Intraoperative Period ; Male ; Middle Aged ; Myocardial Ischemia ; Myocardium ; metabolism ; Thromboxane A2 ; metabolism

OBJECTIVETo investigate the reactivity of intrapulmonary arterial rings to vasoactive substances as thromboxane A2 and endothelin-1 in patients with chronic obstructive pulmonary disease (COPD).

METHODSIntrapulmonary arterial rings isolated from patients with normal lung function and COPD were mounted in a Multi Myograph system to determine the reactivity of the intrapulmonary arterial rings to 60 mmol/L KCl, thromboxane A2 analogue U46619 and endothelin-1 before and after preconditioning with the COX synthase inhibitor indomethacin.

RESULTSThe reactivity of intrapulmonary arterial rings to U46619 and endothelin-1 was significantly decreased in patients with COPD. The reactivity to U46619 was dramatically decreased in patients with normal lung function after application of indomethacin.

CONCLUSIONThe reactivity of intrapulmonary arterial rings is significantly decreased in patients with COPD.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ; pharmacology ; Aged ; Endothelin-1 ; metabolism ; Female ; Humans ; In Vitro Techniques ; Indomethacin ; pharmacology ; Male ; Middle Aged ; Pulmonary Artery ; metabolism ; Pulmonary Disease, Chronic Obstructive ; metabolism ; Thromboxane A2 ; metabolism

OBJECTIVETo study the change of vascular tension factors (VTF), including vascular contractile factors as endothelin-1 (ET-1), thromboxane A2 (TXA2) and vascular dilatory factors as nitric oxide (NO), prostacyclin (PGI2), in different stage of peripheral diabetic arterial occlusion (PDAO), and to preliminarily explore the clinical significance of these changes.

METHODSVTF in 40 diabetic patients, 15 of 2nd stage and 25 of 3rd stage, were observed by measuring level of ET-1, NO, TXB2 and 6-keto-PGF1alpha in blood plasma with RIA assay.

RESULTS(1) ET-1 and TXB2 levels in all patients were higher than those in control (P < 0.05 and P < 0.01), those in patients of 3rd stage was higher than those of 2nd stage, showing significant difference (P < 0.05). (2) NO and 6-keto-PGF1alpha levels in all patients was lower than those in control, but showed no significant difference between patients of various stages (P > 0.05).

CONCLUSIONThere are changes of VTF in patients with PDAO, manifesting as increase of vascular contractive factors and decrease of vascular dilative factor. The changes are diffrent in various stages, the vascular contractive and thrombotic factors in patients of 3rd stage are higher than those in patients of 2nd stage, but the injury on vascular dilative factors in the two stages showed insignificant difference.

6-Ketoprostaglandin F1 alpha ; blood ; Aged ; Aged, 80 and over ; Diabetes Mellitus, Type 2 ; metabolism ; Diabetic Angiopathies ; metabolism ; physiopathology ; Endothelin-1 ; blood ; Epoprostenol ; blood ; Female ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Nitric Oxide ; blood ; Thromboxane A2 ; blood ; Thromboxane B2 ; blood ; Vasomotor System ; metabolism