Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purposes of the present study were to examine the natural course of the impairment of endothelium-dependent relaxations during a regeneration and tissue repair process after balloon endothelium removal and to elucidate the cellular mechanism(s) underlying it. Twenty-three male Yorkshire pigs underwent balloon endothelium removal along the proximal portion of either the left anterior descending or circumflex coronary artery and were then maintained on a regular chow for 4, 8, 16, or 24 weeks. Endothelium-dependent responses were examined in vitro in rings taken from the control and previously denuded arteries studied in parallel. Morphometric analysis revealed that intimal thickening developed only at the previously denuded area. In the previously denuded arteries with regenerated endothelium, the endothelium-dependent relaxations to UK 14304 (a selective alpha 2-adrenergic agonist), serotonin, and aggregating platelets were impaired 4 weeks after endothelium removal and remained so throughout the study. The endothelium-dependent relaxations to thrombin and adenosine diphosphate became depressed 8 weeks after endothelium removal and those to bradykinin became depressed 16 weeks after endothelium removal, while those to the calcium ionophore A23187 were maintained throughout the study. Endothelium-dependent relaxations to all vasoactive agents were unaltered in the control arteries. In the control arteries, pertussis toxin, an inhibitor of certain G proteins, markedly inhibited the endothelium-dependent relaxations to UK 14304 and serotonin and partially inhibited those to thrombin and aggregating platelets. The responses inhibited by the toxin in control arteries were significantly reduced in the reduced in the previously denuded arteries with regenerated endothelium. The inhibitory effect of pertussis toxin was markedly reduced in those arteries with regenerated endothelium. In quiescent rings, the presence of normal endothelium inhibited the contractions caused by serotonin and aggregating platelets; this endothelium-dependent depression was markedly impaired in the previously denuded arteries throughout the study. Direct relaxation of the coronary smooth muscle to nitric oxide or sodium nitroprusside or direct contraction to KCl or serotonin were comparable between the control and previously denuded arteries. These experiments indicate that endothelium-dependent relaxations progressively worsen after regeneration of the endothelium and that the dysfunction of a pertussis toxin-sensitive G protein partly account for the endothelial dysfunction in the chronic regenerated state.
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PMID:Natural course of the impairment of endothelium-dependent relaxations after balloon endothelium removal in porcine coronary arteries. Possible dysfunction of a pertussis toxin-sensitive G protein. 250 8

Plasma fibrinopeptide A levels, beta-thromboglobulin levels and platelet factor 4 levels were estimated by enzyme-linked immunosorbent assay before and after hyperventilation in 12 patients with coronary vasospastic angina and in 12 control subjects matched for age and gender. In all 12 study patients, anginal attacks accompanied by electrocardiographic (ECG) changes (ST elevation in 11 patients and ST depression in 1 patient) were induced by hyperventilation. Coronary angiography was performed on 11 of the 12 patients, and coronary artery spasm with the same ECG changes was induced by intracoronary injection of acetylcholine in all 11. The plasma fibrinopeptide A levels increased significantly from 2.0 +/- 0.4 to 10.0 +/- 2.4 ng/ml during the attack (p less than 0.001) in the study patients, but remained unchanged before and after hyperventilation in the control subjects. The plasma levels of beta-thromboglobulin and platelet factor 4 remained unchanged after hyperventilation in both groups. Our data indicate that coronary artery spasm may induce thrombin generation and trigger thrombus formation in the coronary artery.
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PMID:Increased plasma fibrinopeptide A levels during attacks induced by hyperventilation in patients with coronary vasospastic angina. 252 82

Serial changes of FPA, FPB beta 15-42, FN, XIIIa, and alpha 2PI were investigated for the study on wound healing, blood coagulation, and fibrinolysis during gastric cancer surgery. For a control, we compared the preoperative values with the postoperative ones. These results also were compared with the values in healthy volunteers and in patients with cholelithiasis or myoma uteri. Our findings were as follows; 1) Compared with the control values, a statistically significant elevation of FPA, FPB beta 15-42 and FPA/FPB beta 15-42 ratios in patients with gastric cancer was noticed after operation. 2) Compared with the control values, a statistically marked decrease of FN, XIIIa and alpha 2PI in patients with gastric cancer was observed after operation. 3) The preoperative FPA and FPB beta 15-42 levels of gastric cancer patients were appreciably greater than those of normal healthy volunteers. Compared with patients with cholelithiasis or myoma uteri, however, the only preoperative FPA of gastric cancer patients showed significantly high levels. 4) FN and alpha 2PI revealed a notable positive correlation. These results suggest (1) increase of coagulation activity (thrombin formation) in gastric cancer patients; (2) increase of intravascular coagulation and fibrinolytic activity (thrombin and plasmin formation) during gastric cancer surgery; and, (3) depression of FN, XIIIa and alpha 2PI during surgery was due to sequestration at the site of tissue injury.
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PMID:[Wound healing, blood coagulation and fibrinolysis during operations involving gastric cancer surgery]. 256 16

Administration of heparin (2 un) into rats with depression of the anticoagulation system before treatment of the animals with alpha-thrombin (8 NIH un) inhibited the enzyme interaction with blood fibrinogen, which was manifested as a distinct decrease in content of soluble fibrin in blood as compared with its concentration evaluated after the treatment with thrombin. Heparin inhibited the reaction of thrombin with specific receptors in vascular walls. The effector response of the anticoagulation system, which is specific for interaction of free alpha-thrombin with the cell wall receptors, was not observed if thrombin was administered intravenously together with heparin. The patterns of the anticoagulation system were not altered after administration of the equimolar complex of DIP (diisopropyl phosphoryl)-alpha-thrombin and heparin, although free DIP-alpha-thrombin activated distinctly the anticoagulation system. The data obtained suggest that heparin, which inhibits partially the recognition site in thrombin molecule, impaired also the enzyme ability to bind to the specific receptors of vascular walls and therefore it impaired the distinct response of the anticoagulation system.
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PMID:[Heparin-induced impairment of thrombin interaction with fibrinogen and receptors of the anti-coagulation system]. 301 36

After 90 min. of partial venous occlusion (40%) in dog's femoral vein plasminogen activator (t-PA) was decreased in the pre-occlusion segment and maintained in the post-occlusion segment. Prostacyclin-like activity (PLA) was maintained in the pre-, but increased in the post-occlusion segment. Treatment with heparin (loading dose-70/kg; IV perfusion-1 U/kg/min) did not affect pre-treatment pattern of t-PA or PLA in either segments. Treatment with aspirin (IV perfusion-2 mg/kg/min) promoted profound depression of PLA in both segments while t-PA remained unchanged. Treatment with lidocain (loading dose-1.5 mg/kg; IV perfusion 0.2 mg/kg/min) did not affect either PLA or t-PA in the pre-occlusion segment, but a decrease of these two activities was observed in the post-occlusion segment. We conclude that, since thrombin, prostaglandins and white blood cells were not responsible for all changes observed at t-PA and PLA vessel wall levels, it is justified, to evaluate the role of rheological factors as the probable determinant of these changes.
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PMID:Local plasminogen activator and prostacyclin-like activity after partial venous occlusion--an experimental study in the dog. 304 44

Complexes antithrombin III-heparin-thrombin exhibiting the anticoagulation and nonenzymatic fibrinolytic activities were isolated from human blood children of 4-II years old with burns or with traumatic shock and from rat blood. The complexes antithrombin III-heparin-thrombin with high nonenzymatic fibrinolytic activity were shown to develop during activation of the anticoagulation system. In depression of the anticoagulation system these complexes, isolated from blood, demonstrated the lower nonenzymatic fibrinolytic activity, thus indicating that complex-formation is restricted.
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PMID:[The role of the antithrombin III-heparin-thrombin complex in the defense reaction of the anticoagulation system]. 340 Jan 89

The inhibitory effects of sulfinpyrazone are more marked ex vivo than in vitro, suggesting biotransformation to potentially active metabolites such as the sulfide and sulfone metabolites. As a platelet inhibitor, the sulfide metabolite is 10 times as potent as the parent and because of its long t1/2, the former may lead to cumulative inhibition of platelet function in vivo during chronic sulfinpyrazone dosing. In our study, healthy subjects received sulfinpyrazone, 200 mg four times a day, for 6 days. Plasma levels of the sulfide metabolite rose slightly from 2.1 +/- 0.8 micrograms/ml 12 hr after the fourth dose to 2.8 +/- 0.8 microgram/ml 12 hr after the twenty-fourth dose. This was associated with increasing inhibition of ex vivo platelet aggregation induced by platelet-activating factor during the dosing period, but inhibition of arachidonic acid-induced aggregation did not increase cumulatively during dosing and collagen-induced aggregation was not inhibited. Inhibition of platelet aggregation was no longer evident 24 hr after the final dose of sulfinpyrazone. The effects of sulfinpyrazone on cyclooxygenase activity were assessed by measurement of thromboxane B2 production by thrombin-stimulated platelets ex vivo and urinary excretion of the major prostacyclin metabolite 2,3-dinor-6-keto-PGF1 alpha. During sulfinpyrazone dosing, thromboxane formation and prostacyclin biosynthesis were correspondingly lowered 50% to 60%. The extent of this depression was of the same order on days 2 and 5 of dosing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclooxygenase inhibition, platelet function, and metabolite formation during chronic sulfinpyrazone dosing. 391 87

We examined the effect of fibrinolysis depression on thrombin-induced pulmonary microembolism in awake sheep prepared with chronic lung lymph fistulas. Fibrinolysis was depressed by an intravenous infusion (100 mg) of tranexamic acid [trans-4-(Aminomethyl)cyclohexanecarboxylic acid]. Pulmonary microembolism was induced by an intravenous infusion of alpha-thrombin (80 NIH U/kg) in normal (n = 7) and in tranexamic acid-treated (n = 6) sheep. Thrombin immediately increased pulmonary lymph flow (Qlym) in both groups. The increased Qlym was not associated with a change in the lymph-to-plasma protein concentration (L/P) ratio in the control group and with a small decrease in the tranexamic acid-treated group. The increases in Qlym and pulmonary transvascular protein clearance (Qlym X L/P ratio) in the tranexamic acid-treated group were greater and sustained at four- to fivefold above base line for 10 h after the thrombin and remained elevated at twofold above base line even at 24 h. In contrast, Qlym and protein clearance were transiently increased in the control group. The mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) increased after thrombin in tranexamic acid-treated group; the increases in Ppa and PVR in the control group were transient. Protein reflection coefficient as determined by the filtration independent method decreased after thrombin in tranexamic acid-treated sheep (n = 5), indicating an increased vascular permeability to proteins. We conclude that prolongation of microthrombi retention in the pulmonary circulation results in an increased vascular permeability to proteins. Both increased vascular permeability and vascular hydrostatic pressure are important determinants of the increases in Qlym and transvascular protein clearance after thrombin-induced pulmonary microembolism.
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PMID:Thrombin-induced alterations in lung fluid balance in awake sheep. 399 9

Endotoxin administered intravenously to a group of four calves resulted in disseminated intravascular coagulation. A sublethal dose of piromen, a commercially available Pseudomonas spp endotoxin, was used. Serial measurements of total plasma fibrinogen, soluble fibrin levels, ethanol gelation tests, protamine sulfate tests, fibrinogen-fibrin-related antigen (FR-antigen) and prothrombin and thrombin times were done.Initial depression of plasma fibrinogen with a nadir of about 40% of pre-endotoxin levels at eight to 11 hours post-endotoxin (+8 to +11 hours) followed by an overcompensation to 180% at +60 to +108 hours was shown. Soluble fibrin was demonstrated in plasma from +2 to +22 hours with a peak of 100-114 mg/100 ml at +4 to +9 hours. Positive plasma ethanol gelation and protamine sulfate tests, as well as the presence of serum FR-antigen, occurred consistently following endotoxin administration. Significant increases in prothrombin times (PT) from +4 to +40 hours and in thrombin times (TT) from +4 to +16 hours were demonstrated. The peak increase of PT at +8 to +10 hours was 180%. The peak increase of TT at +6 to +9 hours was 260-290%.
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PMID:Endotoxin induced disseminated intravascular coagulation in cattle. 427 65

Thrombin and poly-l-lysine alter the incorporation of acetate, glycerol, and fatty acids into the lipids of washed human platelets. Both aggregating agents decrease the incorporation of acetate into all lipid classes other than free fatty acids. Similarly, glycerol incorporation into complex lipids is impaired by both thrombin and polylysine. Thrombin caused marked depression of the incorporation of palmitic acid into both lecithin and triglycerides. By contrast it enhanced the incorporation of oleic acid into lecithin, but not into triglycerides. The data suggest that the process of primary platelet aggregation is associated with a defect in the assembly of complex lipids.
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PMID:Altered lipid metabolism in human platelets after primary aggregation. 468 85


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