Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preeclampsia is associated with increased thromboxane and decreased prostacyclin production by the placenta. Low-dose aspirin can selectively inhibit thromboxane production in the adult circulation, but its effects on placental vascular production of thromboxane and prostacyclin are incompletely understood. We therefore studied the effects of low-dose aspirin on the production rates of prostacyclin and thromboxane, with and without vasoconstricting doses of angiotensin II, in human placental arteries. Chorionic plate arteries were incubated and samples were assayed for thromboxane and prostacyclin by radioimmunoassay of their stable metabolites. Production rates for prostacyclin were similar in the control, aspirin, angiotensin II, and angiotensin II plus aspirin groups. Mean (+/- SEM; n = 8) thromboxane production rates in the aspirin (1.4 +/- 0.5 pg/mg/hr) and angiotensin II plus aspirin (2.9 +/- 0.6 pg/mg/hr) groups were significantly lower (p less than 0.05) than values in the control (8.6 +/- 2.7 pg/mg/hr) and angiotensin II (6.7 +/- 1.3 pg/mg/hr) groups. We conclude that low-dose aspirin significantly decreases production of thromboxane in placental arteries both with and without vasoconstricting doses of angiotensin II.
 ...
PMID:Low-dose aspirin inhibits thromboxane, but not prostacyclin, production by human placental arteries. 306 Dec 95

The dilator stimuli that contribute to postasphyxial increases in cerebral blood flow in the neonate are unclear. To assess the possible role of cyclooxygenase products in these responses, we measured pial arteriolar diameter in six piglets and determined levels of prostaglandin (PG) E2 and 6-keto-PG F1 alpha (hydrolysis product of PGI2) in cerebrospinal fluid (CSF) bathing the parietal cortex during control conditions, after 4-10 min of complete respiratory arrest (asphyxia), and after 5-12 min of reventilation. Pial arterioles are important resistance vessels in the cerebral circulation. Baseline pial arteriolar diameter was 220 +/- 40 micron (mean +/- SEM) and increased to a maximum of 252 +/- 49 and 267 +/- 56 micron after asphyxia and reventilation, respectively. During control conditions, CSF PGE2 (n = 6) and 6-keto-PGF1 alpha (n = 4) levels were 1947 +/- 310 and 794 +/- 147 pg/ml, respectively. During asphyxia, CSF levels of PGE2 did not increase, whereas 6-keto-PGF1 alpha increased modestly. During reventilation, CSF PGE2 increased to 3576 +/- 499 pg/ml, and 6-keto-PGF1 alpha increased to 2846 +/- 123 pg/ml. In other experiments, we determined that these CSF levels of PGE2 and PGI2 (as 6-keto-PGF1 alpha) were within the vasodilator range for pial arterioles. We conclude that postasphyxial increases in pial arteriolar diameter are associated with a rise in CSF levels of dilator prostanoids.
 ...
PMID:Postasphyxial increases in prostanoids in cerebrospinal fluid of piglets. 314 95

Streptozotocin induced diabetic rat hearts were perfused under constant flow conditions with or without 1 x 10(5) U.litre-1 each of superoxide dismutase and catalase (SOD + CAT). Total global ischaemia was produced for 20 min followed by 30 min of reperfusion at pre-ischaemic flow rates. After 5 min of reperfusion, isovolumic LV developed pressure was reduced in diabetic hearts, at 22 (SEM 11)% of baseline v 67(12)% in controls, with increased frequency of ventricular fibrillation (VF) (3/10 v 10/11 hearts). SOD + CAT improved isovolumic LV developed pressure to 67(8)% of baseline during early reperfusion of diabetic hearts but did not affect non-diabetic hearts. SOD + CAT also increased the adenylate energy charge potential in post-ischaemic diabetic hearts to 0.826(0.011) v 0.781(0.012) in diabetic controls, and reduced the incidence and duration of reperfusion induced VF in diabetic hearts. SOD + CAT augmented the production of prostacyclin in coronary effluents during early reperfusion of diabetic hearts, from (baseline) 11.5(1.7) to 18.1(3.0) ng.min-1.g-1 at 2 min, compared with 11.1(1.6) to 12.5(1.9) ng.min-1.g-1 at same interval in diabetic controls. Indomethacin prevented the protective effect of the free radical scavengers on function and VF. In contrast, perfusion with the prostacyclin analogue, iloprost (3 x 10(-8) M), alone completely prevented early post-ischaemic dysfunction and reduced VF from 559(172) to 16(8) s. Oxygen derived free radicals may mediate reperfusion induced contractile dysfunction and VF in acutely diabetic hearts following brief episodes of myocardial ischaemia. The beneficial effects of SOD + CAT appear to be mediated mainly by an increase in prostacyclin production during early reperfusion.
 ...
PMID:Superoxide dismutase plus catalase improves post-ischaemic recovery in the diabetic heart. 325 31

Prostaglandin (PG) formation in 16 atherosclerotic human carotid endarterectomy specimens was compared systematically with that of normal carotid artery from seven white pigs and six rhesus monkeys. Prostacyclin (PGI2) formation (picomoles 6-keto-PGF1a/2 min/100 micrograms homogenate protein plus 2 mM glutathione [GSH]) of nonatheromatous intima adjacent proximal (276 +/- 32, mean +/- SEM) or distal (271 +/- 14) to carotid plaque was comparable to that of normal carotid artery from white pig (272 +/- 25, NS) and rhesus monkey (219 +/- 41, NS), and was greater than stenotic intima (156 +/- 17, p less than 0.01), subintimal plaque (168 +/- 14, p less than 0.01), and ulceration (65 +/- 16, p less than 0.01). GSH modulated PGI2 synthesis in all carotid specimens except areas of ulceration (p less than 0.05), but did not restore PGI2 formation in atheromatous fractions to basal level. No detectable arterial thromboxane A2 (TXA2) formation or GSH-dependent PGE2 isomerase activity was observed. The decrement in atherosclerotic carotid artery PGI2 formation was focal (confined to the plaque) and may have been related to loss of effective GSH modulation. These conditions could contribute to a localized imbalance between arterial PGI2 and platelet TXA2 with adverse vascular thromboregulatory consequences.
 ...
PMID:Prostacyclin, thromboxane A2, and prostaglandin E2 formation in atherosclerotic human carotid artery. 327 12

We hypothesized that chronic ischemia of peripheral vascular disease would lead to increased thromboxane A2 (TxA2) and decreased prostacyclin (PGI2) production and surgical correction of the ischemia would stabilize TxA2 and PGI2 at normal levels. TxA2 and PGI2 concentrations were determined in 22 patients before, during, and after arterial reconstruction for limb salvage and in 10 control subjects. Control samples and preoperative patient samples had no detectable TxA2 or PGI2 (less than 26 pg/ml). Five minutes after reperfusion TxA2 increased (TxA2 = 76.27 +/- 48.9 pg/ml, mean +/- SEM) and persisted at 1 day (TxA2 = 190.1 +/- 80.1 pg/ml), 2 days (TxA2 = 224.7 +/- 131.7 pg/ml), 5 days (TxA2 = 334.8 +/- 272.8 pg/ml), and 7 days postoperatively (TxA2 = 256.6 +/- 149.0 pg/ml). Elevated TxA2 production was not associated with chronic ischemia of peripheral vascular disease. Reperfusion of the severely ischemic limb caused significant TxA2 release.
 ...
PMID:Thromboxane release after reperfusion of chronically ischemic limbs in patients. 328 Aug 35

Epidermal growth factor (EGF) stimulated prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells, as measured by radioimmunoassay of its stable metabolite 6-keto-prostaglandin F1 alpha. This effect of EGF was dose-dependent, the lowest stimulatory concentration of EGF was 1.0 ng/ml and 100 ng/ml caused a 2.7 +/- 0.3 (mean +/- SEM) fold increase in the PGI2 synthesis. The stimulation appeared at 3-6 h of incubation and lasted at least 24 h. It was suppressed by EGF antibodies and blocked by protein synthesis inhibitor cycloheximide. Cells preincubated 12 h with EGF released also higher amounts of PGI2 when incubated with thrombin for 5 min. It is concluded that EGF liberated from platelets during aggregation may prevent local thrombogenesis and atherogenesis by stimulating the release of the antiaggregatory, vasodilatory PGI2 from vascular endothelial cells.
 ...
PMID:Epidermal growth factor stimulates prostacyclin production by cultured human vascular endothelial cells. 329 Nov 83

Six anesthetized dogs treated with indomethacin, prostacyclin (PGI2), and heparin were compared with 7 anesthetized controls (ischemia without treatment) to determine whether cyclooxygenase inhibition would lead to enhanced granulocyte accumulation because of preferential formation of lipoxygenase products. Cortical somatosensory evoked response, [14C]iodoantipyrine autoradiographic blood flow, and 111In-labelled granulocyte accumulation were compared 4 hours after a 60-minute exposure to multifocal brain ischemia. Treatment with indomethacin, PGI2, and heparin eliminated neuron-disabling brain blood flows without altering early postischemic granulocyte accumulation. Granulocyte accumulation after 4 hours of reperfusion was not significantly different in control and treated dogs. The final amplitude of the cortical somatosensory evoked response in the treated group averaged 38.0 +/- 13.6% (mean +/- SEM) of the corresponding baseline value compared with 21.0 +/- 4.6% in the control group, but this difference was not significant.
 ...
PMID:Indomethacin, prostacyclin, and heparin improve postischemic cerebral blood flow without affecting early postischemic granulocyte accumulation. 329 33

Repeated transfusions with platelets from randomly selected donors lead to HLA alloimmunization in about 50% of patients due to lymphocyte contamination of platelet concentrates. Attempts to remove the leukocytes from the platelet concentrates by additional centrifugation steps led to substantial loss of platelets. We report a new procedure for removal of almost all leukocytes with excellent platelet recoveries. Single donor concentrates are treated with 50 ng/mL prostacyclin to inactivate the platelets transiently. The concentrates are then passed through a cellulose-acetate filter to remove the leukocytes. In 30 concentrates this treatment reduced the contamination by leukocytes to less than 0.1 million per concentrate with a platelet recovery of 89% +/- 1% (mean +/- SEM). Thirty filtered platelet concentrates transfused to ten thrombocytopenic patients within one hour after filtration were well tolerated and led to corrected count increments of (22.0 +/- 1.1) X 10(6)/mL blood after one hour and normal survival thereafter. In four of five patients these concentrates reduced the bleeding time. We conclude that transient inactivation of platelets by prostacyclin enables optimal removal of leukocytes and may help to reduce alloimmunization during frequent transfusions with platelet concentrates.
 ...
PMID:Clinical experience with transfusion of leukocyte-poor platelet concentrates prepared by filtration with prostacyclin. 329 2

The effects of PGI2 and PGE1 on the ultrastructure of human platelets were studied by scanning (SEM) and transmission (TEM) electron microscopy in relation to the record of an optical aggregometer. Addition of PGI2 or PGE1 to citrated platelet-rich plasma (C-PRP) resulted in a permanent slight decrease in percent light transmission (%T) recorded by the aggregometer. SEM investigation of the platelets showed marginal pseudopods and occasional large stomata after application of prostaglandins. These alterations occurred within the initial 30 s and remained constant during the subsequent 20 min of incubation. TEM studies revealed morphological changes of alpha granules and moderately electron-dense material in the dilated profiles of the surface-connected canalicular system (SCCS). Addition of 10 microM ADP to C-PRP preincubated for 30 s with either 2 ng/ml (5 nmol/liter) PGI2 or 30 ng/ml (85 nmol/liter) PGE1 resulted in a further decrease of %T followed by a slight increase. The alterations of the aggregometer tracing were characterized in SEM by platelet shape change and the generation of primary aggregates. C-PRP samples preincubated with 3 and 9 ng/ml (8 nmol/liter and 24 nmol/liter) PGI2 or 40 and 120 ng/ml (113 nmol/liter and 338 nmol/liter) PGE1 did not produce additional changes in the aggregometer curves or in the ultrastructure of platelets in response to ADP. Our morphological study indicates that antiaggregatory prostaglandins induce an early phase of platelet activation but inhibit "shape change" and the formation of aggregates.
 ...
PMID:PGI2 and PGE1 induce morphological alterations in human platelets similar to those of the initial phase of activation. 330 81

Biochemical (or functional) adaptation of venoarterial grafts has been demonstrated recently. We reexamined one aspect of this biochemical "arterialization" process: prostacyclin (PGI2) production by canine venoarterial autologous grafts and the responsiveness of this biosynthetic pathway to maximal stimulation with substrate enhancement. Four reversed autologous grafts (femoral vein) were interposed into both carotid and femoral arteries in eight dogs. After 12 weeks, the grafts were removed, and radioimmunoassay was used to determine luminal surface production of 6-keto-PGF1 alpha (the stable metabolite of PGI2) in both the basal and stimulated (27 mumol/L arachidonic acid [AA]) states. PGI2 production by the venous autologous grafts was compared with that of control native artery and vein. We confirmed that PGI2 production (measured in nanograms per milliliter) by control artery was greater than vein under both basal conditions (5.8 +/- 0.4 [+/- SEM] vs. 2.7 +/- 0.5, p less than 0.001) and stimulated conditions (8.8 +/- 0.8 vs. 5.5 +/- 0.4, p = 0.002); moreover, AA stimulation significantly increased PGI2 production in both native artery and vein compared with basal PGI2 production. Under basal conditions, graft PGI2 production (6.3 +/- 1.6 ng/ml) was not significantly different than basal arterial levels (p = 0.8) but was higher than basal venous levels (p = 0.05). However, in marked contrast to both native artery and vein, the vein graft flow surface showed no significant response to substrate enhancement with AA: basal (6.3 +/- 1.6 ng/ml) vs. stimulated (5.9 +/- 0.9 ng/ml) (p = 0.8). These observations confirm that canine venoarterial autologous grafts undergo biochemical "arterialization"; however, this process appears to be an incomplete one.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Incomplete biochemical adaptation of vein grafts to the arterial environment in terms of prostacyclin production. 331 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>