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

The nonsteroidal anti-inflammatory agent, zomepirac, was evaluated for its in vivo antithrombotic effects in conscious canines by inducing left circumflex (LCX) coronary artery thrombosis with low-amperage electrical stimulation (50 muA for 24 h) of the intimal surface of the vessel. Zomepirac, 10 mg/kg i.v., given at 0 and 12 h, prevented occlusive coronary artery thrombosis (seven of 10 controls developed occlusive thrombi, compared to one of eight zomepirac-treated animals; p = 0.02). LCX thrombus mass also was reduced by zomepirac (control: 24.0 +/- 4.0 mg; zomepirac: 10.2 +/- 2.4 mg, p less than 0.05; means +/- SEM). Left ventricular infarct mass due to occlusive LCX coronary artery thrombosis was likewise reduced. In a separate series of experiments, zomepirac (10 mg/kg i.v.), given 30 min before occlusion, failed to limit the extent of irreversible myocardial injury after temporary (90 min) LCX coronary artery occlusion in the canine. Infarct size, as a percent of the area at risk of infarction, averaged 47.8 +/- 3.9% in controls, and 40.4 +/- 7.5% in zomepirac-treated animals (means +/- SEM). No difference in the mass of myocardium at risk of infarction was observed between the two groups. In this latter study, zomepirac produced no significant hemodynamic effects. Ex vivo platelet aggregation in response to collagen and arachidonic acid was decreased significantly by zomepirac, but aggregation to ADP was unaffected. These results suggest that zomepirac possesses anti-thrombotic properties, but lacks intrinsic cardioprotective effects. Therefore, zomepirac may be of potential value in the prevention of coronary artery thrombosis owing to its ability to modify platelet reactivity.
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PMID:Effect of zomepirac on experimental coronary artery thrombosis and ischemic myocardial injury in the conscious dog. 618 7

To determine the effect of improved, short-term glycemic control on various functions of hemostasis in insulin-dependent diabetes, we measured changes in plasma fibrinogen, fibrinopeptide A (FPA), functional antithrombin III (AT-III), factor VIII:ristocetin cofactor ( VIIIRCoF ), beta-thromboglobulin (BTG), platelet factor 4 (PF4), and platelet aggregation responses to ADP and collagen in 12 patients with low or undetectable stimulated (postprandial) serum C-peptide levels during 4-8 wk (median, 6 wk) of treatment with constant subcutaneous insulin infusion. Mean plasma fibrinogen, FPA, AT-III, VIIIRCoF , and BTG at baseline were elevated compared with normal. Three patients had heightened platelet responses to ADP that did not correlate to other indicators of a hypercoagulable state; the affected patients, in fact, had significantly lower plasma BTG (25.5 +/- 5.3 [SEM] versus 44.6 +/- 4.6 ng/ml, P less than 0.05) and FPA (1.1 +/- 0.1 versus 2.5 +/- 0.5 ng/ml, P less than 0.05) than the remaining patients. Patients with clinically evident vascular disease had higher baseline plasma BTG and FPA than those without vascular disease (44.6 +/- 5.4 versus 30.2 +/- 4.6, and 2.6 +/- 0.6 versus 1.3 +/- 0.2 ng/ml, P less than 0.05, respectively). During treatment, all patients had declining blood glucose (200 +/- 18 to 102 +/- 5 mg/dl, P less than 0.001) and HbA1 (11.8 +/- 0.6 to 10.2 +/- 0.4%, P less than 0.005). No statistically significant changes in hemostatic functions were noted. During treatment, one patient had an acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma beta-thromboglobulin, platelet factor 4, fibrinopeptide A, and other hemostatic functions during improved, short-term glycemic control in diabetes mellitus. 620 89

Although numerous studies have provided indirect evidence for enhanced platelet activity in sickle cell anaemia, little attention has been directed to examination of platelet alpha and dense granule release in the sickling disorders. We simultaneously measured by radioimmunoassay plasma levels of the alpha granule constituents beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in 43 children with sickle cell anaemia in steady state and 24 patients during severe vaso-occlusive crisis. beta-TG levels during steady state (50 +/- 3.6 ng/ml, mean +/- SEM) were greater (P less than 0.001) than in normal controls (36 +/- 1.6), but there was no additional significant rise during crisis (55 +/- 5.9). PF4 levels were similar (P = 0.12) in both steady state (10 +/- 1.2 ng/ml) and crisis (9.3 +/- 2.3) to those of normal controls (6.0 +/- 0.8). The similarity of beta-TG/PF4 ratios in normal and sickle cell anaemia patients as well as the positive correlation (P less than 0.05) between platelet count and beta-TG and PF4 suggested that an artefactual in vitro platelet activation was responsible for some of the observed increased beta-TG and PF4 levels. Further evidence against enhanced platelet activity in these sickle cell patients included normal intraplatelet content of the dense granule constituent 5-HT and a normal ATP/ADP ratio. From this data we conclude that platelet activation in children with sickle cell anaemia appears minimal.
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PMID:Evidence against enhanced platelet activity in sickle cell anaemia. 622 55

Factor Xa binds to platelets provided that factor Va is present on the platelet surface, an interaction that results in a striking acceleration of the conversion of prothrombin to thrombin. Thrombin then initiates fibrin formation, induces platelet aggregation, and stimulates the intraplatelet synthesis of thromboxane A2 (TXA2). Addition of thrombin (2.4-14.4 nM) to platelet-rich plasma increased the basal level of TXA2, measured as thromboxane B2, from less than 0.5 pmol per 10(8) platelets to (mean +/- SEM) 100 +/- 22 and 250 +/- 10 pmol per 10(8) platelets, respectively. Treatment of platelet-rich plasma with increasing concentrations of factor Xa (1-12 nM) prior to the addition of thrombin progressively inhibited the production of TXA2. Thrombin (9.6 nM), which produced 93% of the maximal formation of TXA2, was inhibited 70% by factor Xa (10 nM). To identify which of these steps in thromboxane synthesis was inhibited by factor Xa, platelets labeled with [14C]arachidonic acid were exposed to thrombin and products of prostaglandin synthesis were separated by thin-layer chromatography. In contrast to the inhibition of TXA2 synthesis, prostaglandin E2 and prostaglandin F2 alpha synthesis were not inhibited suggesting that neither phospholipase(s) nor cycloxygenase was involved. The inhibition of TXA2 formation by factor Xa could be reversed by increasing the molar ratio of thrombin to factor Xa to 5.5. Incubation of platelets with an IgG fraction of a human monoclonal antifactor V antibody, previously shown to inhibit factor Xa binding, was found to block factor Xa inhibition of TXA2 synthesis. The inhibition of TXA2 synthesis requires the presence of the active site serine of factor Xa and is not specific for TXA2 formation induced by thrombin because it is also demonstrable when the agonist is ADP. Further, factor Xa does not require additional plasma components for its action because its inhibitory effects are detected in gel-filtered platelets. The effect of factor Xa was evident at physiological (1.3 mM) calcium concentrations. These results indicate that factor Xa binding to platelets through factor Va not only stimulates thrombin formation but also has a countervailing effect by inhibiting TXA2 formation.
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PMID:Inhibition of thromboxane A2 synthesis in human platelets by coagulation factor Xa. 657 68

Acute vasospasm of the transclivally exposed basilar artery of anesthetised cats was produced by the subarachnoid injection of platelet-rich plasma (PRP) treated with enough adenosine diphosphate (ADP) to induce platelet aggregation and secretion. Vasorelaxation was produced by the topical application of the calcium antagonist verapamil. Changes in the internal diameter of the basilar artery were determined by measuring the blood column diameter from photomicrographs taken sequentially, at 5 minute intervals, through the operating microscope. Changes in blood vessel diameter are expressed as a plus or minus percentage of the pretreatment diameter. Arterial blood pressure and blood gas values were kept in the physiological range for the cat. The subarachnoid injection of PRP-ADP produced severe constriction of the basilar artery (mean constriction at 5 minutes after injection: -40.7% +/- 2.8 SEM). Platelet-free plasma, ADP alone and Elliott's A solution had no spasmogenic effect when injected into the subarachnoid space. The topical application of the calcium channel blocker verapamil (0.1 mg per kg) 30 minutes after the injection of PRP-ADP, with the basilar artery still in spasm (mean constriction: -23% +/- 3.5 SEM), produced prompt and dramatic vasodilation (mean dilation at 5 minutes after application: +52.7% +/- 18.1 SEM). This spasmolytic effect persisted in a decremental fashion for the 60 minute period of observation, by which time the previously constricted vessel had returned to its normal size. These observations indicate that the platelet fraction of whole blood may be involved in the genesis of acute vasospasm following subarachnoid hemmorrhage and that this phenomenon can be readily reversed by calcium antagonism.
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PMID:Reversal of acute experimental cerebral vasospasm by calcium antagonism with verapamil. 670 93

We recently described a monoclonal antibody, 10E5 , that completely blocks adenosine diphosphate (ADP) induced fibrinogen binding to platelets and aggregation induced by ADP, epinephrine, and thrombin. Multiple lines of evidence indicate that 10E5 binds to platelet membrane glycoproteins IIb and/or IIIa. Because it has been reported that platelets treated with chymotrypsin aggregate when fibrinogen is added, we tested the effect of 10E5 antibody on chymotrypsin-induced fibrinogen binding and platelet aggregation. Aspirin-treated human platelets were washed in modified Tyrode's buffer (pH 7.5), incubated for 5 minutes at 22 degrees C with 300 micrograms/mL chymotrypsin, and washed again. The amount of 10E5 antibody bound to these platelets (37,232 +/- 2,928 molecules/platelet; mean +/- SEM, N=9) was similar to that bound to unstimulated control platelets (36,910 +/- 2,669) and did not differ significantly from the amount of antibody bound to ADP-treated platelets (P less than .01, N = 5). The amount of 10E5 bound to chymotrypsin-treated platelets correlated directly with the amount of fibrinogen bound to separate aliquots of the same platelet samples (r = .876, P less than .001). The 10E5 antibody caused virtually complete inhibition of both the binding of fibrinogen to chymotrypsin-treated platelets and the aggregation induced by exogenous fibrinogen. Immunoprecipitation studies of 125I-labeled chymotrypsin-treated platelets revealed that the 10E5 antibody bound proteins with molecular weights characteristic of glycoproteins IIb and IIIa. These data suggest that the fibrinogen receptor on chymotrypsin-treated platelets is identical to that on ADP-treated platelets and that this receptor is either near to, or on, the glycoprotein IIb/IIIa complex.
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PMID:A murine monoclonal antibody that blocks fibrinogen binding to normal platelets also inhibits fibrinogen interactions with chymotrypsin-treated platelets. 673 83

45Calcium uptake was studied with aspirin-treated platelets that were gel-filtered through a column of Sepharose 2B equilibrated with divalent cation-free modified Tyrode's solution to remove readily exchangeable surface-associated calcium. These platelets aggregated almost immediately when exposed to ADP, fibrinogen and at least 30 microM CaCl2. At this calcium ion concentration, 10(8) platelets took up 36.6 +/- SEM 2.7 pmol of 45calcium within 1-2 min. The presence of ADP and fibrinogen did not affect the amount of calcium bound. Over 90% of this platelet-associated calcium was removed by EDTA in 5 min suggesting that it was surface-bound. Calcium uptake increased rapidly for 10 min, then more slowly for up to 2 h. At 60 min, maximal uptake was approached at CaCl2 concentrations between 250 and 300 microM when an average of 276 +/- SEM 18 pmol of calcium was associated with 10(8) platelets. Only 50-60% of this calcium could be removed by EDTA in 5 min, and about 70% in 20 min, suggesting that some of it had been internalized. Platelets from two patients with thrombasthenia that were unable to aggregate took up 50% less calcium than platelets from normal volunteers. Similarly, platelets that had been incubated with EDTA at 37 degrees C, pH 7.8 for 8 min lost the ability to aggregate despite recalcification and took up 40-60% less calcium than CaEDTA-treated controls. Platelets from a patient with the Bernard-Soulier syndrome aggregated and bound calcium normally. Thus the platelets' ability to take up calcium after removal of surface-associated calcium correlates with their ability to aggregate. Since thrombasthenic platelets and platelets rendered incapable of aggregating after prolonged calcium deprivation with EDTA do not bind fibrinogen, we postulate that some of the surface-associated calcium normally binds to the fibrinogen receptors.
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PMID:Decreased association of 45calcium with platelets unable to aggregate due to thrombasthenia or prolonged calcium deprivation. 677 78

Since 1966, 29 patients with recurrent carotid artery stenosis have been encountered. The mean (+/- SEM) internal between initial carotid endarterectomy and secondary presentation was 67.5 +/- 9.2 months (range 6 to 180 months). There was a disproportionate number of women with recurrent stenosis. The mean age at initial endarterectomy in patients with recurrent stenosis, 54.6 +/- 1.4 years, was significantly less (P less than 0.001) than that of all patients who had endarterectomy. To define the etiologic factors for recurrence, 21 of these patients were matched with case-control patients of the same age and sex who had undergone endarterectomy the same year but did not develop recognized recurrent stenosis. There was no significant difference in the incidence of hypertension, diabetes mellitus, coronary artery disease, bilateral carotid disease, other vascular operations, or family history for atherosclerosis in patients with recurrent stenosis compared to control patients. The indications for primary endarterectomy, angiographic distribution of disease, and operative details were similar in both groups. There was no difference in the incidence of regular, therapeutic aspirin ingestion following initial endarterectomy (52.5% in both groups). There was a striking difference in smoking habits. Ninety-five percent of patients with recurrent stenosis continued to smoke following initial endarterectomy, compared to 23.8% of control patients (P less than 0.001). Lipid fractionation studies were performed in both groups, and there were no significant differences in levels of cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, and total cholesterol/HDL-cholesterol ratio. Dose-response platelet aggregometry detected no differences between groups in the sensitivity of platelets to adenosine diphosphate (ADP), collagen, and epinephrine. Reoperation in patients with recurrent stenosis was associated with minimal morbidity, no deaths, and generally excellent results.
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PMID:Etiologic factors for recurrent carotid artery stenosis. 682 70

Mitochondria were isolated from the hepatopancreas of the Florida spiny lobster Panulirus argus using a high osmolarity medium containing 600 mM mannitol, 83 mM sucrose, 5 mM 4-morpholinepropanesulfonic acid, pH 7.6, 0.5% bovine serum albumin (BSA), and 1 mM EDTA. O2 uptake and Ca2+ transport were measured by electrode methods in similar media (plus 4 mM KPi, 3.3 mM MgCl2, and 0.67 mg/ml BSA, with 80 mM KCl replacing a portion of the osmotic support). Substrate-supported respiration was observed to be coupled to phosphorylation of ADP or uptake of Ca2+ ions. State 3 rates (nanogram atoms O X minute-1 X milligram protein-1 +/- SEM (N)) were: 49.2 +/- 3.9 (19), succinate; 30.9 +/- 3.9 (6), DL-palmitoyl carnitine; 29.0 +/- 2.7(9), L-malate; 40.0 +/- 2.3(3), L-glutamate; 27.7 +/- 2.2(5), D-3-hydroxybutyrate; and 26.4 +/- 2.4 (18), L-proline +/- pyruvate. alpha-Glycerol phosphate was not oxidized. Ca2+ uptake driven by succinate oxidation proceeded with Ca:O ratios of 4.0 +/- 0.2 (SEM). Hepatopancreas mitochondria were not uncoupled by Ca2+ uptake in excess of 1100 ng atoms X mg protein-1. Ca2+ efflux could be induced by ruthenium red, indicating the presence of an active Ca2+ cycle. These mitochondria may provide a favorable model system in which to study regulation of the Ca2+ cycle.
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PMID:Respiratory and calcium transport properties of spiny lobster hepatopancreas mitochondria. 687 Feb 85

Changes in myocardial purine metabolism were studied after temporary coronary artery occlusion and subsequent reperfusion in the dog. Sequential myocardial biopsies were performed to allow for measurements of ATP, adenine nucleotide, nucleoside, and base concentrations after 15 min of ischemia, and after 90 min and 72 hr of reperfusion following this period of ischemia. Control, nonischemic sites were also sampled. After 15 min of coronary occlusion, subendocardial ATP concentrations (reported in nmol/mg of protein; mean +/- SEM) were depressed in the ischemic zone at 19.9 +/- 3.5 compared to 38.1 +/- 2.8 in the nonischemic zone (P < 0.001). Subepicardial ATP concentrations also were depressed at 27.0 +/- 2.2 in ischemic sites compared to subepicardial nonischemic sites (40.0 +/- 4.0, P < 0.005). After 90 min of reperfusion ATP concentrations remained depressed in the previously ischemic subendocardium 26.8 +/- 4.2 (P < 0.025 vs. nonischemic sites). After 72 hr of reperfusion, ATP was still depressed in the previously ischemic subendocardium at 29.2 +/- 2.5 (P < 0.025 vs. nonischemic) and subepicardium (27.9 +/- 3.3, P < 0.05 vs. nonischemic). Total purines were determined as the sum of ATP, ADP, AMP, adenosine, inosine, and hypoxanthine. After 15 min of occlusion, the total purine pool in the ischemic subendocardium tended towards being lower than in the nonischemic zone (42.0 +/- 5.9 vs. 53.8 +/- 5.2, not significant) but in the ischemic subepicardium the total purine pool was similar to that in the nonischemic zone. After 90 min of reperfusion the previously ischemic subendocardial purine pool was reduced compared to the nonischemic zone (39.0 +/- 4.8, P < 0.025). Total purines were also depleted in both the subendocardium and subepicardium of previously ischemic zones after 72 hr of reperfusion (44.5 +/- 2.9 and 40.0 +/- 4.4, respectively, P < 0.05). Histologic analysis of the previously ischemic tissue revealed no evidence of necrosis. Therefore, brief temporary coronary artery occlusions not associated with anatomic evidence of necrosis may result in prolonged abnormalities of ATP concentration and significant depletion of the total purine pool.
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PMID:Prolonged derangements of canine myocardial purine metabolism after a brief coronary artery occlusion not associated with anatomic evidence of necrosis. 693 66


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