OBJECTIVE: There is no proven regimen to reduce the severity of stroke in patients with acute cerebral infarction presenting beyond the thrombolytic time window. Ozagrel sodium, a selective thromboxane A2 synthetase inhibitor, has been known to suppress the development of infarction. The antiplatelet effect is improved when aspirin is used together with a thromboxane synthetase inhibitor. METHODS: Patients with non-cardiogenic acute ischemic stroke who were not eligible for thrombolysis were randomly assigned to two groups; one group received ozagrel sodium plus 100 mg of aspirin (group 1, n=43) and the other 100 mg of aspirin alone (group 2, n=43). Demographic data, cardiovascular risk factors, initial stroke severity [National Institute of Health Stroke Scale (NIHSS) and motor strength scale] and stroke subtypes were analyzed in each group. Clinical outcomes were analyzed by NIHSS and motor strength scale at 14 days after the onset of stroke. RESULTS: There were no significant differences in the mean age, gender proportion, the prevalence of cardiovascular risk factors, stroke subtypes, and baseline neurological severity between the two groups. However, the clinical outcome for group 1 was much better at 14 days after the onset of stroke compared to group 2 (NIHSS score, p=0.007, Motor strength scale score, p<0.001). There was one case of hemorrhagic transformation in group 1, but there was no statistically significant difference in bleeding tendency between two groups. CONCLUSION: In this preliminary study, thromboxane A2 synthetase inhibitor plus a low dose of aspirin seems to be safe and has a favorable outcome compared to aspirin alone in patients with acute ischemic stroke who presented beyond the thrombolytic time window.
Aspirin ; Cerebral Infarction ; Hemorrhage ; Humans ; Infarction ; Methacrylates ; Prevalence ; Risk Factors ; Sodium ; Stroke ; Thromboxane A2 ; Thromboxane-A Synthase ; Tissue Plasminogen Activator

OBJECTIVETo investigate the association between the polymorphism of the thromboxane synthase gene and Uigur patients with myocardial infarction (MI) in Xinjiang.

METHODSThree hundred and fifteen patients with MI and 218 healthy control subjects were detected by polymerase chain reaction and restriction fragment length polymorphism. The serum thromboxane B2 (TXB2) in all subjects was detected with radioimmunoassay kit.

RESULTSThe genotype distributions of the MI group and control group were in Hardy-Weinberg equilibrium (Chi-square=0.375,0.029, P>0.05). The frequencies of CC and TC were 0.933 and 0.067 in MI group while they were 0.977 and 0.023 in controls. There was significant difference in frequencies of the TC genotype and T allele but no difference in frequencies of CC genotype between controls and MI cases. There was significant difference in serum TXB2 level between the MI and control group (P<0.05), and between individuals of the TC and CC genotypes (P<0.05). The serum TXB2 level in the MI cases with TC genotype was increased compared with that of other genotypes (P<0.05).

CONCLUSIONThe TC genotype and T allele of thromboxane synthase gene might be risk factors of MI in Uigur population in Xinjiang, which might result from the increased serum TXB2 level.

Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Case-Control Studies ; China ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Myocardial Infarction ; blood ; enzymology ; ethnology ; genetics ; Polymorphism, Genetic ; Thromboxane B2 ; blood ; Thromboxane-A Synthase ; genetics

OBJECTIVETo investigate the association between the polymorphism of thromboxane synthase gene (CYP5A1) and myocardial infarction (MI) of Uigur nationality patients in Xinjiang.

METHODSRs10487667 site polymorphism in CYP5A1 gene of 318 patients with MI (MI group) and 232 healthy control subjects (control group) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. The serum thromboxane B(2)(TXB(2)) concentration was also detected in all subjects. The relationship of multiple factors and myocardial infarction was evaluated comprehensively by non-condition logistic regression analysis.

RESULTSThe frequencies of CYP5A1 gene Rs10487667 site polymorphism in MI group and control group were: GG type 0.204 (65/318) and 0.155 (36/232), GT type 0.553 (176/318) and 0.466 (106/232), TT type 0.242 (77/318) and 0.379 (88/232), respectively. There was significant difference in frequencies of GG genotype (χ(2) = 12.193, P = 0.002) between two groups and G allele frequency in MI group (0.481 (306/636)) was significant higher than control group (0.388 (180/464)) (χ(2) = 9.449, P = 0.021), but no difference in frequencies of GT and TT genotypes (χ(2) = 0.699, P > 0.05)between controls and MI cases. There was significant difference in serum TXB(2) level between MI ((184.3 ± 34.7) pg/ml) and control ((124.3 ± 28.1) pg/ml) groups (t = 5.503, P = 0.034). In the case and control group, the serum TXB(2) level of the person with GT + GG genotype ((164.21 ± 22.56) and (134.26 ± 19.83) pg/ml)) was significant higher than those of TT genotypes ((113.67 ± 54.23) and (98.54 ± 13.11) pg/ml) (t values were 5.433 and 5.108, respectively, both P values < 0.05). Logistic regression analysis showed that the T allele of the CYP5A1 gene was one independent risk factor of MI (OR = 1.673, 95%CI: 1.020 - 2.156) after adjustment of risk factors.

CONCLUSIONRs10487667 polymorphism in CYP5A1 gene might be a risk factor of MI in Uigur population in Xinjiang, which maybe related with the significant high serum TXB(2) level.

Alleles ; Case-Control Studies ; China ; epidemiology ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; epidemiology ; genetics ; Polymorphism, Genetic ; Thromboxane B2 ; blood ; Thromboxane-A Synthase ; genetics

BACKGROUND: Endothelin-1 is a potent vasoconstrictor substance that causes slow and longlasting contractions of isolated blood vessels. In the aorta of the spontaneously hypertensive rat, endothelin-1 stimulates the release of a cyclooxygenase-dependent, endothelium-derived contracting factor(EDCF), presumably thromboxane A2. There have not been any studies about the response of porcine coronary arteries with regenerated endothelium to endothelin-1. METHODS: The present study was designed to determine the role of EDCF in the response to endothelin-1 in arteries with regenerated endothelium. Rings of porcine coronary arteries, with and without endothelium of previously deendothelialized left anterior descending coronary artery and native left circumflex coronary arteries, were suspended in conventional organ chambers for the measurement of isometric force. RESULTS: In quiescent rings of the previously deendothelialized left anterior descending coronary artery treatd with the nitric oxide synthase inhibitor nitro-Larginine, endothelin-1 caused contractions which were larger in the rings with edothelium than in those without endothelium. Under the same experimental conditions, in the left circumflex coronary artery, the contractions to edothelin-1 were significantly greater by the removal of the endothelium. In rings with endothelium of the previously deendothelialized left anterior descending coronary artery, indomethactin(inhibitor of cyclooxygenase) and ridogrel(thromboxane A2 receptor antagonist, and inhibitor of thromboxane synthase) shifted the concentration-response curve to endothelin-1 to the right and to a comparable extent. Dazoxiben(inhibitor of thromboxane syndthase) and BQ-123(selective antagonist of endothelin-A receptor subtype) inhibited, to the same extent as indomethacin and ridogrel, the response to higher concentrations of endothelin-1. The endothelium-dependent component of the response to lower concentrations of endothelin-1 was inhibited by indomethacin and ridogrel, but not by dazoxiben and BQ-123. In rings without endothelium of both previously deendothelialized left anterior descending and native left circumflex coronary arteries, indomethacin and ridogrel did not affect the contractions to endothelin-1. CONCLUSION: These findings suggest that in regenerated endothelium, high concentrations of endothelin-1 stimulate the release of thromboxane A2 through activation of edothelin-A receptors. Endoperoxides generated by activation of endothelial cyclooxygenase may be the endothelium-derived contracting factor(s) released in regenerated endothelium by lower concentrations of the peptide.
Aorta ; Arteries ; Blood Vessels ; Coronary Vessels* ; Endothelin-1 ; Endothelium* ; Indomethacin ; Nitric Oxide Synthase ; Prostaglandin-Endoperoxide Synthases ; Rats, Inbred SHR ; Thromboxane A2*

OBJECTIVETo assess the association of cytochrome P450 gene single nucleotide polymorphisms (SNPs) with susceptibility to gout in ethnic Han males from coastal regions of Shandong province.

METHODSFour hundred and eighty male patients with gout and 480 healthy male controls were included. Genotyping was carried out with a custom Illumina GoldenGate Genotyping assay to detect SNP rs2275620 of CYP2C8 gene, SNP rs2070676 of CYP2E1 gene, SNP rs837395 of CYP4B1 gene, and SNP rs194150 of TBXAS1 gene. The association was assessed with chi-square test.

RESULTSNo significant difference has been found between the two groups in regard to the genotypic and allelic frequencies of the TT, AT, AA genotypes and A, T alleles of the SNP rs2275620 of the CYP2C8 gene (P=0.88; P=0.97), the CC, CG, GG genotypes and C,G alleles of SNP rs2070676 of the CYP2E1 gene (P=0.24; P=0.09), the TT, AT, AA genotypes and A, T alleles of SNP rs837395 of the CYP4B1 (P=0.88; P=0.97), and TT, AT, AA genotypes and the A,T alleles of SNP rs194150 of TBXAS1 gene (P=0.15; P=0.06).

CONCLUSIONThis study has identified no association of SNP loci rs2275620(A/T) of CYP2C8, rs2070676(C/G) of CYP2E1, rs837395(A/T) of CYP4B1 and rs194150(A/T) of TBXAS1 with gout in ethnic Han males from coastal regions in Shandong province. However, our result needs to be replicated in larger sets of patients collected from other regions and populations.

Adult ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Cytochrome P-450 CYP2C8 ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; Disease Susceptibility ; Female ; Gout ; enzymology ; ethnology ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Thromboxane-A Synthase ; genetics

Coronary artery disease is a common occurrence in human, and causes enormous social cost. Poncirus fructus (PF), the dried immature fruits of Poncirus trifoliata Rafinesquem, is used in the treatment of womb contraction and dyspepsia, as a prokinetic, and in improving blood circulation. This study was performed to investigate the effects of PF and some of its flavonoids components on the coronary from the pig. The arterial ring was suspended by a pair of stainless steel stirrups in an organ bath. The end of the upper stirrup was connected to an isometric force transducer. A dose-dependent induction of relaxation was observed by both water and 70% ethanol extracts of PF in the porcine coronary artery precontracted with U46619 (100 nM), a stable analogue of the potent vasoconstrictor thromboxane A2. The 70% ethanol extract showed more efficacy than the water extract. Pretreatment of the artery with L-NAME (100 microM), a nitric oxide synthase inhibitor, resulted in a significant reduction in the relaxation induced by PF extract. In addition, ODQ (10 microM), a soluble guanylate cyclase inhibitor, also significantly reduced the effects of PF extracts. Hesperidin, a flavonoid present in PF, induced very weak relaxation of the porcine coronary artery at a high concentration (100 microM), while its aglycone, hesperetin, demonstrated a dose-dependent relaxation. In conclusion, PF extracts induced relaxation in the porcine coronary artery, partially through the nitric oxide-cGMP pathway, and the aglycones of flavonoids might be also involved in the relaxation of the same artery.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ; Arteries ; Baths ; Blood Circulation ; Coronary Artery Disease ; Coronary Vessels* ; Dyspepsia ; Ethanol ; Flavonoids ; Fruit ; Guanylate Cyclase ; Hesperidin ; Humans ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Poncirus* ; Relaxation ; Stainless Steel ; Thromboxane A2 ; Transducers ; Water

BACKGROUND AND OBJECTIVES: Previous studies have shown that integrins alpha5beta1 (ITGA5B1) gene-modified rat bone marrow mesenchymal stem cells (rBMSCs) could prevent cell anoikis and increase the nitric oxide (NO) production. Here we examined the capability of rBMSCs/ITGA5B1 on the phenotype modulation of Human Pulmonary Artery Smooth Muscle Cell (HPASMC) in vitro. METHODS AND RESULTS: The synthetic (dedifferentiated) phenotype of HPASMC was induced by monocrotaline (MCT, 1μM) for 24 h and then co-cultured with rBMSCs/ITGA5B1 in a transwell culture system. The activation of NO/cGMP (nitric oxide/Guanosine-3′, 5′-cyclic monophosphate) signaling was investigated in HPASMC. The changes of pro-inflammatory factors, oxidative stress, vasodilator, vasoconstrictor, contractile and synthetic genes, and the morphological changes of HPASMC were investigated. The results of this study showed that the NO/cGMP signal, endothelial nitric oxide synthase (eNOS) expression, the expression of the vasoprotective genes heme oxygenase-1 (HMOX1) and prostaglandin-endoperoxide synthase 2 (PTGS2) were increased, but the expression of transforming growth factor-β1 (TGF-β1), CCAAT/enhancer-binding proteins delta (Cebpd), Krüppel-like factor 4 (KLF4), and activating transcription factor 4 (ATF4) were reduced in MCT treated HPASMC co-cultured with rBMSCs/ITGA5B1. The synthetic smooth muscle cells (SMCs) phenotype markers thrombospondin-1, epiregulin and the vasoconstrictor endothelin (ET)-1, thromboxane A2 receptor (TbxA2R) were down-regulated, whereas the contractile SMCs phenotype marker transgelin expression was up-regulated by rBMSCs/ITGA5B1. Furthermore, rBMSCs/ITGA5B1 promoted the morphological restoration from synthetic (dedifferentiation) to contractile (differentiation) phenotype in MCT treated HPASMC. CONCLUSIONS: rBMSCs/ITGA5B1 could inhibit inflammation and oxidative stress related genes to promote the HPASMC cell differentiation by activation NO/cGMP signal.
Activating Transcription Factor 4 ; Animals ; Anoikis ; Bone Marrow ; Cell Differentiation ; Endothelins ; Epiregulin ; Genes, Synthetic ; Heme Oxygenase-1 ; Humans ; In Vitro Techniques ; Inflammation ; Integrins ; Mesenchymal Stromal Cells ; Monocrotaline ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Nitric Oxide Synthase Type III ; Nitric Oxide ; Oxidative Stress ; Phenotype ; Prostaglandin-Endoperoxide Synthases ; Pulmonary Artery ; Rats ; Receptors, Thromboxane A2, Prostaglandin H2