6-ketoprostaglandin-f1-alpha and Thromboembolism

We have used the EaHy926 endothelial cell line, able to secrete both pro and anti-aggregant platelet agents, as a model for thrombo-embolic diseases. We experimentally established, by comparing these two secretions with or without a Faraday cage, that the environmental electromagnetic field significantly increases the thrombo-embolic risks in this endothelial cell line.

Topics: 6-Ketoprostaglandin F1 alpha; Cell Line; Electromagnetic Fields; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Epoprostenol; Humans; Risk Factors; Thromboembolism; Thromboxane A2; Thromboxane B2

To observe the changes of thromboxane B(2) (TXB(2)), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) and anticardiolipin antibody (ACA) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after institution of nasal continuous positive airway pressure (nCPAP).. Sixty cases of OSAHS confirmed by polysomnography (PSG) were selected as the trial group, and 20 normal donors without OSAHS were recruited as the control group. Nineteen patients with severe OSAHS were treated by nCPAP. Plasma levels of TXB(2), 6-K-PGF1alpha were detected by enzyme-linked immunosorbent assay (ELISA).. Plasma (serum) level of TXB(2) (ACA) was significantly higher in patients with moderate to severe OSAHS than that in control group (P < 0.01), and nCPAP therapy decreased its level significantly (P < 0.01). Plasma level of 6-K-PGF1alpha was significantly lower than that in the control group (P < 0.01), and nCPAP therapy increased its level significantly (P < 0.01). TXB(2) and ACA were correlated positively with AHI, and negatively with minimal oxygen saturation (P < 0.01). 6-K-PGF1alpha was correlated negatively with AHI, and positively with minimal oxygen saturation (P < 0.01).. The results indicate that patients with OSAHS are susceptible to thromboembolism disease. TXB(2), 6-K-PGF1alpha, ACA may be associated with the high prevalence of thromboembolism in patients with OSAHS. nCPAP therapy is effective in correcting TXB(2), 6-K-PGF1alpha, ACA.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Antibodies, Anticardiolipin; Continuous Positive Airway Pressure; Female; Humans; Male; Middle Aged; Sleep Apnea, Obstructive; Thromboembolism; Thromboxane B2

To evaluate the effects of lupus anticoagulant (LA) on pulmonary thromboembolism (PTE).. Thirty-eight patients with PTE (17 massive and 21 submassive) and 30 healthy adults were studied. Russell's viper venom time (RVVT) was used to examine the ratio of LA (LAR), and a colorimetric method was used to detect the activity of plasma protein C (PC:A) and radioimmunoassay (RIA) was employed to measure the level of plasma thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha).. Compared with the normal group, LAR, TXB(2) and TXB(2)/6-keto-PGF1alpha showed significant increase in the massive PTE and the submassive PTE groups (P < 0.01), and the levels were higher in the massive group than in the submassive group (P < 0.01). Both groups showed significant decrease in PC:A and 6-keto-PGF1alpha compared with the normal group (P < 0.01).. LA can increase TXB(2)/6-keto-PGF1alpha and decrease PC:A in patients with PTE. It is suggested that there may be an association between the increase of LAR and the presence of PTE.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; C-Reactive Protein; Female; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Prostaglandins; Pulmonary Embolism; Radioimmunoassay; Thromboembolism; Thromboxane B2

A series of 1H-imidazol-1-yl- and 3-pyridyl-substituted 3,4-dihydroquinolin-2(1H)-ones was designed and synthesized as combined inhibitors of thromboxane (TXA2) synthase and cAMP phosphodiesterase (PDE) in human blood platelets. A number of structures, e.g. 4b, 7a, 7e, 13a, and 21-25, were superior to dazoxiben 26 as inhibitors of TXA2 synthase in in vitro ADP-induced aggregation experiments with human blood platelets. The TXA2 synthase inhibitory activity was confirmed by measurement of the prostanoid metabolites derived from 14C-labeled arachidonic acid. Three compounds (7a, 7e, and 25) demonstrated in vitro inhibition of human platelet cAMP PDE at micromolar concentrations in conjunction with their TXA2 synthase inhibitory activity. Synergistic enhancement of antiaggregatory and antithrombotic actions was expected when simultaneous stimulation of adenylate cyclase (through increased PGI2 production) and inhibition of platelet cAMP PDE were possible from the same compound. Ex vivo and in vivo experiments were conducted in rats and mice, respectively, to evaluate the effects of compounds 7e and 23 on platelet aggregation and thrombotic events within these animals. Compound 7e, which has a comparable level of TXA2 synthase (IC50 1.2 microM) and human platelet cAMP PDE (IC50 6.4 microM) inhibitory activities, was found to be orally bioavailable with a long duration of action and offered effective protection against mortality in a collagen-epinephrine-induced pulmonary thromboembolism model in mice. Significant blood pressure and heart rate effects were observed for several compounds, e.g. 7e, 9e, 13a, 13d, 18, 20, 21, and 23, when dosed orally in conscious spontaneously hypertensive rats.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Animals; Aorta; Blood Platelets; Fibrinolytic Agents; Humans; Hypertension; Male; Microsomes; Platelet Aggregation; Platelet Aggregation Inhibitors; Quinolones; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Swine; Thromboembolism; Thromboxane B2; Thromboxane-A Synthase

To elucidate the mechanism of vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant changes in factors associated with haemostasis were investigated. The lupus anticoagulant was associated with an increased incidence of thrombosis, particularly cerebral thrombosis. Concentrations of fibrinopeptide A and fibrinopeptide B beta 15-42 were significantly raised in the plasma of patients with systemic lupus erythematosus and the anticoagulant compared with concentrations in patients without the lupus anticoagulant. The tendency towards formation of thrombosis was not found in all lupus patients with the anticoagulant, however. Concentrations of thromboxane B2 were remarkably raised in the plasma of the two patients with the lupus anticoagulant who had recently had thrombosis. Concentrations of 6-keto-prostaglandin F1 alpha, protein C, antithrombin III, and plasminogen were similar in both groups. No significant decrease in serum stimulatory activity on prostacyclin production by cultured aortic endothelial cells was noted in lupus patients with the anticoagulant, but inhibition was present in the two patients with recent thrombosis. These results indicate that although patients with the lupus anticoagulant are not always in a hypercoagulable state, haemostatic abnormalities found in some patients with the anticoagulant may be predictive of thrombotic events.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Animals; Antibodies; Blood Coagulation Factors; Cardiolipins; Cattle; Female; Hemostasis; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Middle Aged; Thromboembolism; Thrombosis

Thromboxane++ (TX), prostacyclin (PC) and platelet factor IV (PF) were assayed using radioimmune kits in 46 patients with cardiac fibrillation secondary to coronary heart disease and rheumatic fever. The study established elevated TX beta 2 levels, low concentrations of 6-ketoPGF1 alpha, enhanced activity of PF. Restoration of the sinus rhythm by electroimpulse treatment (EIT) brought about augmentation of the Tx-Pc-PF unbalance on day 2-3. This may give rise to "normalization" thromboembolism. On days 5-7 after EIT the intensity of platelet aggregation and PF secretion diminish. It is concluded that patients with sudden cardiac fibrillation in need of sinus rhythm correction will benefit from disaggregation and anti-coagulant therapy.

Topics: 6-Ketoprostaglandin F1 alpha; Atrial Fibrillation; Electric Countershock; Humans; Platelet Factor 4; Thromboembolism; Thromboxane B2; Time Factors