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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A procedure for preparing highly enriched suspensions of bovine binucleate trophoblastic cells was developed and data showing that these cells produce progesterone, prostacyclin (PGI2), and prostaglandin E2 (PGE2) were obtained. Approximately 200 X 10(6) enzymatically dissociated cells from bovine cotyledons were applied to the surface of a density gradient of 2% to 4% Ficoll-400 using the Wescor CELSEP sedimentation chamber. After 90-120 min of sedimentation at unit gravity, fractions containing binucleate trophoblastic cells were obtained and washed in HEPES-buffered Medium 199. Preparations of 90% to 100% binucleate trophoblastic cells were obtained routinely; viability was 50% to 80%. After incubation at 37 degrees C, concentrations (ng/10(5) cells) of progesterone were greater in those fractions containing binucleate cells than in those containing primarily smaller, mononucleate cells. Total progesterone secreted (mean +/- SEM) after 4 h by 1 X 10(5), 2 X 10(5), 4 X 10(5), 8 X 10(5), and 1.6 X 10(6) binucleate cells was 0.27 +/- 0.03, 1.01 +/- 0.09, 4.02 +/- 0.37, 10.31 +/- 0.92, and 20.96 +/- 2.23 ng, respectively (r = 0.997). Addition of 10% fetal bovine serum (FBS) or normal anestrous cow serum increased (P less than 0.05) production of progesterone by binucleate trophoblastic cells. Luteinizing hormone, follicle-stimulating hormone, prolactin, thyrotropin, and 8-bromo-adenosine 3',5'-cyclic monophosphate had no effect. Binucleate trophoblastic cells also produced PGI2 in relation to number of cells incubated (r = 0.996). Time courses for production of PGI2, PGE2, and progesterone were similar. Aspirin inhibited production of PGI2 and PGE2 by about 50% at a dose of 100 microM; FBS stimulated production of both prostanoids.
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PMID:Progesterone and prostanoid production by bovine binucleate trophoblastic cells. 386 92

The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis. 388 Jun 71

Prostacyclin and thromboxane have been implicated in the pathophysiology of several disorders of pregnancy, but there is little information on concentrations of these prostaglandins in normal pregnancy. The aim of our study was to determine the range of values throughout normal pregnancy and the puerperium and to compare this with concentrations in normal non-pregnant women. Measurement was by radioimmunoassay of prostacyclin and thromboxane metabolites. We observed a significant difference in prostacyclin metabolites in the first trimester, (mean 19.9, SEM 0.96 pg/ml) compared with the normal non-pregnant group (mean 15.9, SEM 0.68 pg/ml). There were no significant differences between values in the normal non-pregnant group and those in the second and third trimester or postnatally. The increase in prostacyclin in the first trimester may be associated with placentation and physiological vasodilation, and insensitivity to angiotensin II seen in early pregnancy. We noted a significant reduction in thromboxane metabolites in the second (mean 133, SEM 14.9 pg/ml) and third (mean 123, SEM 10.7 pg/ml) trimesters and the puerperium (mean 119, SEM 6.3 pg/ml) compared with the values in the normal non-pregnant group (mean 142, SEM 4.9 pg/ml). This may be due to increased platelet stability or decreased thromboxane synthesis.
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PMID:Immunoreactive prostacyclin and thromboxane metabolites in normal pregnancy and the puerperium. 389 Sep 36

Whether migration of granulocytes across pulmonary vascular endothelium in the absence of structural evidence of endothelial injury causes increased production of thromboxane or prostacyclin is not known. Using bovine pulmonary artery intimal explants mounted in Boyden chambers and homologous separated granulocytes, concentrations of thromboxane B2 and 6-keto-PGF1 alpha in the upper-well fluid were measured by radioimmunoassay over a three-hour period under the following conditions: (1) granulocyte chemotaxis (zymosan-activated plasma in the lower well, granulocytes in the upper well); (2) unstimulated granulocyte migration (serum or plasma in the lower well, granulocytes in the upper well); (3) granulocyte activation without migration (zymosan-activated plasma and granulocytes in the upper well); (4) granulocyte chemotaxis in the absence of endothelium (identical to condition 1 above except that endothelium was scraped from the explant surface); and (5) explants incubated in the absence of granulocytes. Minimal increases in thromboxane B2 concentrations in upper-well fluid occurred under all conditions. In contrast, granulocyte chemotaxis was accompanied by large increases in concentrations of 6-keto-PGF1 alpha evident by two hours of incubation and increasing markedly by three hours, to 524.3 +/- 69.0 ng/mL (m +/- SEM). Unstimulated migration of granulocytes toward serum or plasma and granulocyte activation without migration were accompanied, at three hours, by more modest increases in 6-keto-PGF1 alpha (296.5 +/- 46.4; 128.0 +/- 38.6, and 236.7 +/- 47.0 ng/mL, respectively) and, in the absence of granulocytes or in the absence of endothelium, only minimal increases in this prostacyclin metabolite occurred (137.2 +/- 16.9 and 53.9 +/- 12.6 ng/mL, respectively). The large rises in prostacyclin metabolite occurred at a time when the majority of granulocytes had migrated through the endothelial layer rather than during their adherence or transendothelial passage. We conclude that chemotaxis of granulocytes through pulmonary vascular endothelium causes endothelial production of large amounts of prostacyclin, but this occurs late in the chemotactic process, after granulocytes have transversed the endothelium.
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PMID:Endothelial prostacyclin production is a late event in granulocyte migration into bovine pulmonary artery intimal explants. 390 71

While fluid shear stress is an important cardiovascular factor in vivo, it has generally been ignored in in vitro assays of endothelial cell function. We quantified the influence of shear stress on the production of prostacyclin by confluent monolayers of bovine aortic endothelial cells placed in a lucite flow chamber and exposed to flowing culture medium at constant shear stress at 37 degrees C and pH 7.4. Continuous inverted-phase microscopy (x 300) of the monolayers showed no significant contraction or detachment of cells under these conditions. Step increases in shear stress from zero to 14 dyne/cm2 caused rapid rises in prostacyclin production, from a baseline (n = 4) of 0.17 +/- 0.062 ng/cm2.min (mean +/- SEM) to peak values within 2 minutes, followed by a decline over several minutes. Peak prostacyclin production increased (p less than 0.005) with shear stress, from 0.60 +/- 0.13 ng/cm2.min at 0.9 dyne/cm2 (n = 14) to 2.33 +/- 0.67 ng/cm2.min at 14 dyne/cm2 (n = 10). The time integral of production or total production, however, did not significantly change with shear stress at least for shear stresses above 0.9 dyne/cm2. Once stressed, cell monolayers produced additional prostacyclin in response to stimulation by Na arachidonate or the calcium ionophore A23187, but not to repeat mechanical stimulation. We conclude that endothelial cells produce bursts of prostacyclin in response to suddenly imposed arterial-like shear stress, and that the peak rate, but not the time integral, of this production increases with shear stress.
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PMID:Prostacyclin production by cultured endothelial cell monolayers exposed to step increases in shear stress. 391 29

To compare the inhibition of human platelet and lung cyclo-oxygenases by sulphinpyrazone (SP), acetylsalicylic acid (ASA) and indomethacin, we investigated their effects on platelet thromboxane A2 (TxA2) production during spontaneous clotting and on prostacyclin (PGI2) and TxA2 productions of superfused minced human lung. The synthesis of proaggregatory, vasoconstricting TxA2 and antiaggregatory, vasodilating PGI2 were evaluated by measuring the concentration of their stable metabolites thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha respectively, by radioimmunoassays. The basal platelet TxB2 production was 241.0 +/- 56.3 ng/ml (mean +/- SEM, n = 12). The concentrations needed for 50% inhibition of this production (IC50) were 41.3 mumol/l for sulphinpyrazone, 6.3 mumol/1 for ASA and 0.094 mumol/l for indomethacin. The lung generated 23.8 +/- 5.5 ng/g/min (mean +/- SEM, n = 6) of 6-keto-PGF1 alpha and 8.5 +/- 1.8 ng/g/min of TxB2. The IC50 values for pulmonary 6-keto-PGF1 alpha and TxB2 productions were 530.0 mumol/l for SP, 370.0 mumol/l for ASA and 50.0 mumol/l for indomethacin. Thus pulmonary cyclo-oxygenase, presumably originating from endothelial cells, was 13, 59, and 532 times more resistant to these prostaglandin synthesis inhibitors (PGI's) than platelet cyclo-oxygenase. These data suggest that there are considerable differences in the concentration ranges of various PGI's by which the PGI2/TxA2 balance can be shifted to a dominance of PGI2.
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PMID:Differential inhibition of platelet thromboxane and lung prostacyclin production by sulphinpyrazone, acetylsalicylic acid and indomethacin by human tissues in vitro. 392 Jul 78

The peritoneal generation of arachidonic acid metabolites was studied in eight patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD) during infection-free periods and during bacterial peritonitis. The prostacyclin metabolite 6-keto-PGF1 alpha was found to be the major prostanoid generated by human peritoneal mesothelium (1090 ng (6h)-1, SEM 86, n = 8) followed by lesser amounts of PGE2 (142 ng (6 h)-1, SEM 26, n = 8), PGF2 alpha (162 ng (6 h)-1, SEM 27, n = 8) and TXB2 (59 ng (6 h)-1, SEM 5, n = 8). During peritonitis a significant increase of all prostaglandins and TXB2 occurred (P less than 0.001). The ratio of the vasodilating prostaglandins and their metabolites (PGE2 and 6-keto-PGF1 alpha) to the vasoconstrictors and their metabolites (PGF2 alpha and TXB2) increased from 6.6 to 10.5 during peritoneal inflammation. Augmented peritoneal clearances of creatinin and urea and increased losses of proteins during peritonitis as well as the enhanced peritoneal generation of prostanoids were reduced to basal values by adequate antibiotic therapy. The present results suggest that the increased peritoneal blood flow during peritonitis, probably responsible for the observed changes of peritoneal transport properties, may be induced by a change in the ratio of vasoactive prostaglandins generated by peritoneal mesothelial cells.
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PMID:Stimulation of peritoneal synthesis of vasoactive prostaglandins during peritonitis in patients on continuous ambulatory peritoneal dialysis. 392 79

The release of vasodilating substances from the vascular endothelium has been postulated to depend on a rise in the level of intracellular free calcium (Cai++). We measured Cai++ in intact monolayers of calf endothelial cells, grown in culture, that were loaded with the fluorescent calcium indicator quin 2. Fluorescence (excitation wavelength 340 nm, emission wavelength 492 nm) was calibrated by raising Cai++ to a maximum with the calcium ionophore ionomycin (0.1 microM) and by lowering it to a minimum with ionomycin plus manganese (0.4 mM), which quenches quin 2 fluorescence completely. Loss of fluorescent dye from the cells was calculated from fluorescence at the isosbestic excitation wavelength (365 nm). Resting Cai++ was 71 +/- 3 (SEM) nM. ATP (adenosine-5'-triphosphate) raised Cai++ dose-dependently and reversibly to 458 +/- 60 nM at a concentration of 10 microM, and at 0.1 mM to values close to those that occurred under ionomycin. ADP (A-5'-PP) and AMP (A-5'-P) had smaller effects with a maximal Cai++ of 287 +/- 72 nM at 30 microM ADP and 176 +/- 17 nM at 0.1 mM AMP. At these concentrations, ADP and AMP attenuated significantly the increase of Cai++ under ATP (10 microM). Adenosine (0.1 or 0.3 mM) and acetylcholine (0.1 to 30 microM) enhanced Cai++ inconsistently, by a maximum of 50 nM. These effects were abolished by theophylline and atropine, respectively. In the absence of extracellular calcium, ATP still raised Cai++, although endothelial responsiveness declined after repetitive stimulations. We conclude that activation of purinergic receptors increases intracellular free calcium in endothelial cells, and that this increase is probably an essential trigger for synthesis of prostacyclin and the labile endothelium-derived relaxant factor.
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PMID:Increased free calcium in endothelial cells under stimulation with adenine nucleotides. 394 90

The release of prostaglandinlike substances from canine pial arteries that was induced by exposure of the pial arteries to red blood cell hemolysate was estimated by using a superfusion technique for prostaglandin bioassay. The assay organs used were strips of rat stomach for prostaglandin E2- or prostaglandin F2 alpha-like substances, strips of dog coronary artery for prostaglandin I2-like substance, and strips of dog ileum for prostaglandin F2 alpha-like substance. The substances released from the canine pial arteries induced contractions in rat stomach strips and relaxations in canine coronary arterial strips, whereas they did not induce any response in canine ileal strips. The equivalent prostaglandin E2 doses for the contractions of the rat stomach strips and the equivalent prostaglandin I2 doses for the relaxations of the canine coronary arterial strips were 125.2 +/- 19.4 (n = 8) and 59.5 +/- 16.4 (n = 6) pmol/g wet wt +/- SEM, respectively.
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PMID:Hemolysate-induced release of prostaglandinlike substances from the canine cerebral arteries. 397 36

Since the vasodilatory, antiaggregatory prostacyclin (PGI2) and its antagonist thromboxane A2 (TxA2) evidently take part in the regulation of the fetoplacental blood flow, the influence of drugs commonly used during pregnancy, such as betamimetics (ritodrine and buphenine) and glucocorticoids (hydrocortisone and dexamethasone), on fetal PGI2 and TxA2 productions was investigated. Specimens of umbilical artery were superfused in vitro without (control) or with the drugs studied (10(-8) - 10(-3) mol/l) and the release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable breakdown product of PGI2, was measured by radioimmunoassay. When studying TxA2 production, umbilical vein blood samples were allowed to clot in the absence and presence of the drugs studied, and the formation of thromboxane B2 (TxB2) a stable breakdown product of TxA2, was measured by radioimmunoassay. Ritodrine and buphenine had no influence on the production of either PGI2 or TxA2, but hydrocortisone and dexamethasone at concentrations of 10(-3) M/l inhibited umbilical PGI2 production to 5.5 +/- 1.4% (mean +/- SEM) and 69.9 +/- 5.0% of the control level, respectively, although they had no effect on TxA2 synthesis. It is concluded that if betamimetics alter the fetoplacental circulation, as suggested by some authors, they do not exert this effect through the fetal PGI2 or TxA2. In contrast, maternal glucocorticoid treatment may suppress fetal PGI2 generation, and thus perhaps reduce the fetoplacental blood flow.
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PMID:The effects of betamimetics and glucocorticoids on fetal vascular prostacyclin and platelet thromboxane synthesis in humans. 615 Nov 93


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