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Biomedical subjects

D Deykin

Publications and source records attributed to D Deykin.

At least 19 recordsLinked to original sources
PubMed1992

Elevated glucose alters A23187-induced release of arachidonic acid from porcine aortic endothelial cells by enhancing reacylation.

Cultured porcine aortic endothelial cells were conditioned in normal (5.2 mM) and elevated (15.6 mM) glucose, prelabeled with [14C]arachidonic acid and stimulated with ionophore A23187. Elevated glucose cultures released less radiolabeled products and less [14C]arachidonic acid. Analysis of cellular lipids revealed that elevated glucose reduced net loss of radiolabel from diacylphosphatidylethanolamine, did not affect early phosphatidylinositol hydrolysis, and increased net loss from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine. Uptake of radiolabel upon stimulation was examined to measure the role of reacylation on the diminished net release of radiolabel in elevated glucose cultures. Enhanced acylation of [3H]arachidonic acid into cellular lipids, especially PI, was observed in stimulated and resting cultures with elevated glucose. Further, pretreatment of the cultures with an acyltransferase inhibitor, thimerosal, prior to A23187 stimulation in radiolabeled cultures, abolished the effects of glucose on eicosanoid and arachidonic acid release. Differences in the ionophore-induced net loss of radiolabel from diacylphosphatidylethanolamine and phosphatidylinositol of the two glucose treatments were diminished by thimerosal exposure, while net loss of radiolabel from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine were unaffected. The data indicate that elevated glucose alters deacylation and enhances reacylation of arachidonic acid into endothelial cells and particularly into phosphatidylinositol. Enhanced reacylation may explain some of the altered lipid pathways that have been observed in experiments that elevate glucose concentrations or involve diabetes.

Acylation↗
PubMed1991

Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group.

OBJECTIVE: To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis. DESIGN: Prospective, randomized, multicenter trial. SETTING: Sixteen university-affiliated Veterans Affairs medical centers. PATIENTS: Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. OUTCOME MEASURES: Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization. INTERVENTION: Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98). RESULTS: At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period. CONCLUSIONS: For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.

Aged↗
PubMed1991

Detection of intracoronary fibrin degradation after coronary balloon angioplasty.

Intracoronary thrombus formation may be involved in the pathogenesis of arterial closure after coronary angioplasty and may contribute to restenosis. It is hypothesized that, unlike markers of platelet activation and fibrin formation, D-dimer, a product of plasmin-mediated proteolysis of cross-linked fibrin, is not subject to significant catheter-induced artifact and could be used to study intracoronary fibrin degradation during angioplasty. No significant difference in D-dimer levels was noted in serial plasma samples obtained from an 8Fr arterial sheath and the wire lumen of an angioplasty balloon catheter, indicating that sampling through the catheter lumen did not induce artifactual D-dimer elevations. Translesion (proximal and distal to the lesion) coronary blood samples were collected in 31 patients undergoing elective coronary angioplasty pretreated with aspirin, dipyridamole and heparin. In 20 of those in whom translesion coronary samples for plasma D-dimer levels (mean +/- standard deviation) were collected before balloon dilation, there was no evidence of ongoing intracoronary fibrinolysis (proximal D-dimer levels, 289 +/- 145 ng/ml; distal, 299 +/- 156 ng/ml; difference not significant). After coronary angioplasty (n = 31), there was a relatively small, but significant (p less than 0.001) increase (45 +/- 71 ng/ml) in translesional D-dimer levels (proximal, 396 +/- 223 ng/ml; distal, 441 +/- 257 ng/ml). The results from this study suggest (1) D-dimer levels are not subject to significant catheter-induced artifact and may be useful for assessment of intracoronary fibrin metabolism, and (2) intracoronary degradation of fibrin can be detected after (but not before) routine coronary angioplasty despite pretreatment with antithrombotic therapy, presumably in response to balloon-induced arterial injury and fibrin formation.

Aged↗
PubMed1991

Issues in the early termination of the aspirin component of the Physicians' Health Study. Data Monitoring Board of the Physicians' Health Study.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled prevention trial of 22,071 US physicians, using a factorial design to evaluate the role of aspirin in the prevention of cardiovascular mortality and beta carotene in the reduction of cancer incidence. After approximately 5 years of follow-up, the aspirin component was terminated, 3 years ahead of schedule. Several factors were considered in the decision to terminate, including a cardiovascular mortality rate markedly lower than expected in both aspirin and placebo subjects, precluding the evaluation of the primary aspirin hypothesis, and a highly significant (P < .00001) and impressive (44%) reduction in the risk of first myocardial infarction in the aspirin group. Issues in the decision to terminate are described in this report.

Adult↗
PubMed1990

Antithrombotic therapy in historical perspective.

The history of antithrombotic therapy is traced over the past 5 decades, with a focus on the treatment of 2 major disorders: venous thromboembolism and acute myocardial infarction. Five subjects pertinent to clinical management decisions are discussed: (1) theories of thrombosis and coagulation, (2) tests of coagulation, (3) the availability of therapeutic interventions, (4) techniques for the diagnosis of vascular obstruction, and (5) the use and misuse of clinical trials.

Anticoagulants↗
PubMed1990

The bleeding time response to aspirin. Identifying the hyperresponder.

The authors measured the template bleeding time in 11 normal people before and 2, 4, 12, 24, and 48 hours after the subjects ingested a single dose of 74 mg of aspirin (ASA). The entire experiment was repeated twice at two-week intervals, with the dose of ASA increased to 325 mg and finally 3,900 mg. The mean increase was maximal at 4 and 12 hours, regardless of the dose administered, with a return to baseline by 48 hours. The authors then performed bleeding times in a prospective randomized double-blinded fashion on an additional 39 subjects at baseline and seven hours after they ingested either placebo or ASA 325 mg. The mean baseline bleeding time was 5.2 minutes (SD +/- 1.4), with a mean prolongation after ASA of 2.1 minutes (SD +/- 1.9). The authors identified 5 of 37 (14%) subjects as hyper-responders (HRs) using the criterion of a bleeding time prolongation of greater than 5.9 minutes (greater than 2 SD beyond the mean prolongation). Neither baseline bleeding time, threshold sensitivity of collagen-induced platelet aggregation, nor other tests of hemostatic function discriminated HRs from normals. The authors conclude that in subjects with normal baseline bleeding times, a prolongation of greater than 5.9 minutes when measured seven hours after the administration of a single dose of 325 mg of ASA can discriminate HRs from normals.

Adult↗
PubMed1990

Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta.

The effects of glucose on endothelium-dependent responses and vasoactive prostanoid production were determined by incubating isolated rabbit aortae in control (5.5 or 11 mM) or elevated (44 mM) glucose for 6 h to mimic euglycemic and hyperglycemic conditions. Rings of aortae incubated in elevated glucose, contracted submaximally by phenylephrine, showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with the aortae incubated in control glucose. Treatment with indomethacin, a cyclooxygenase inhibitor, or SQ29548, a prostaglandin H2/thromboxane A2 receptor antagonist, restored acetylcholine relaxations of rings in elevated glucose to normal, while these agents had no effect on the relaxation of rings incubated in control glucose. Aortae incubated with mannose (44 mM) as a hyperosmotic control relaxed to acetylcholine normally. The relaxations in response to A23187 and sodium nitroprusside were not different between rings exposed to control and elevated glucose. Radioimmunoassay measurements showed a significant increase in acetylcholine-stimulated release of thromboxane A2 and prostaglandin F2 alpha in aortae with, but not without endothelium incubated with elevated, but not with control glucose. Thus a possible mechanism for endothelium dysfunction in diabetes mellitus is the hyperglycemia-induced increased generation of endothelium-derived vasoconstrictor prostanoids.

Acetylcholine↗
PubMed1988

Altered arachidonic acid metabolism and platelet size in atopic subjects.

The release and metabolism of endogenous arachidonic acid (AA) in physiologically activated platelets obtained from 11 atopic patients with allergic rhinitis and/or asthma was compared to that of sex- and age-matched nonatopic controls. Prelabeled [3H]AA platelets were stimulated with thrombin or collagen and the amount of free [3H]AA and radiolabeled metabolites released were measured by high-performance liquid chromatography. The results obtained indicate that although the incorporation of [3H]AA into platelet phospholipids and total release of 3H-radioactivity upon stimulation were comparable in the two groups, the percentage of 3H-radioactivity released from platelets as free AA was significantly lower (P less than 0.01) in the atopic group. The reduction in free [3H]AA was accompanied by an increase (P less than 0.01) in the percentage of 3H-radioactivity released as cyclooxygenase products in atopic platelets (compared to nonatopic cells) after stimulation with 10 and 25 micrograms/ml collagen. The amount of platelet lipoxygenase product released was comparable between the two groups. Although the blood platelet counts were similar, the mean platelet volume was statistically higher (P less than 0.01) in the atopic group. These results indicate that arachidonic acid metabolism in atopic platelets is altered, the pathophysiological significance of which remains to be clarified.

Adult↗
PubMed1988

Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels.

A randomized, placebo-controlled double-blind trial was conducted on 20 adults to assess the effect of vitamin E (800 IU/d 727 mg/d for 5 wk) on platelet function, arachidonic acid metabolism, and prostacyclin generation. Platelet aggregation was measured in response to collagen, arachidonic acid, and adenosine diphosphate. Thromboxane B2 was assayed in serum and in the supernatant plasma after platelet aggregation. Platelets were labeled with [3H]arachidonic acid to assess production and release of cyclooxygenase products (MDA, TXB2, and HHT), a lipoxygenase product (12-HETE), and arachidonic acid in response to stimulation by thrombin or collagen. Prostacyclin was measured in plasma and in blood collected from bleeding-time incisions by a sensitive HPLC-RIA procedure. Despite marked increases in plasma and erythrocyte vitamin E levels in the vitamin E group, there were no significant differences between the vitamin E and placebo groups in any of the variables measured.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Elevated glucose alters eicosanoid release from porcine aortic endothelial cells.

Cultured porcine aortic endothelial cells were conditioned through two passages to mimic euglycemic and hyperglycemic conditions (5.2 mM, normal glucose; 15.6 mM, elevated glucose). After incubation with 1 microM [14C]arachidonic acid for 24 h, the cells were stimulated with 1 microM A23187 for times up to 30 min. Uptake of [14C]arachidonic acid and its distribution among cell lipids were unaffected by the increased glucose concentration. The release of eicosanoids from labeled cells and unlabeled cells was measured by reverse-phase HPLC and by RIA, respectively. Compared with cells stimulated in the presence of normal glucose concentrations, cells stimulated in the presence of elevated glucose released 62.6% less free [14C]arachidonic acid, but released 129% more 14C-labeled 15-hydroxyeicosatetraenoic acid (HETE). Increased release of 15-HETE in the presence of elevated glucose in response to A23187, bradykinin, and thrombin was confirmed by RIA. A similar increase in 5-HETE release was observed by RIA after A23187 treatment. The release of both radiolabeled and unlabeled prostanoids was equal at both glucose concentrations. The data indicate that glucose may play an important role in the regulation of release and metabolism of arachidonic acid after agonist stimulation. In the presence of elevated glucose concentrations, such as those associated with diabetes mellitus, the extent and pattern of eicosanoid release from endothelial cells is markedly altered.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Ionophore-induced metabolism of phospholipids and eicosanoid production in porcine aortic endothelial cells: selective release of arachidonic acid from diacyl and ether phospholipids.

Confluent cultures of porcine aortic endothelial cells were prelabeled with 1 microM [14C]arachidonic acid complexed to 1 microM bovine serum albumin. After washing, the cells were stimulated with 1 microM A23187 for time intervals between 30 s and 30 min. Cellular lipids were extracted and separated into major lipid classes and phospholipid subclasses. The external medium was analyzed for released radioactive eicosanoids. The time-course of total release of 14C radioactivity demonstrated a biphasic nature of A23187-induced changes in endothelial cell lipids. Early, from 30 s to 5 min, substantial losses of [14C]arachidonic acid from diacylphosphatidylethanolamine and phosphatidylinositol, as well as an abrupt increase in diacylphosphatidylcholine-associated radioactivity were observed. These initial changes coincided with the release of 14C-labeled cyclooxygenase products. Later changes (5-30 min) included a sustained progressive loss of 14C radioactivity from alkenyl (alk-1-enyl) acylphosphatidylethanolamine and diacylphosphatidylcholine. These later changes coincided with the elaboration of 14C-labeled lipoxygenase products. Although unequivocal assignments cannot be made, the data suggest that specific pools of arachidonic acid provide precursors for individual classes of eicosanoids.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Incorporation and redistribution of arachidonic acid in diacyl and ether phospholipids of bovine aortic endothelial cells.

The present experiments characterized the incorporation and redistribution of arachidonic acid in diacyl and ether phospholipids of bovine aortic endothelial cells. Confluent cultures were either continuously labeled or pulse labeled with [14C]arachidonic acid. Major lipid classes and ether-linked subclasses of phosphatidyl-ethanolamine (PE) and phosphatidylcholine (PC) were separated by high-performance liquid chromatography and thin-layer chromatography. During continuous labeling, total incorporation of arachidonic acid reached a peak at 8 h and was essentially constant up to 24 h. After 8 h, net label in total PC declined, whereas that in total PE continued to rise. In pulse labeling experiments radioactivity in diacyl PC continuously declined with concomitant increases in both diacyl- and alkenylacyl PE. The data demonstrate that transfer of arachidonic acid from diacyl PC to both diacyl- and alkenylacyl PE occurs in endothelial cells. In contrast to previous observations in platelets, transfer of arachidonic acid to alkenylacyl PE did not require agonist stimulation. This pathway may contribute to the enrichment of endothelial cell PE with arachidonic acid with the potential for subsequent metabolism to prostacyclin.

Acylation↗