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)

Factors affecting fibrin formation and dissolution were compared for 15 women taking combined oral contraceptives and 15 women using nonpharmacological methods of birth control. The two groups were matched for age, body weight, time of blood collection, and day in menstrual cycle; none of the women was receiving other drugs known to affect the blood coagulation or fibrinolytic parameters measured in this study. Fibrinogen concentrations tended to be higher in the experimental group; the degree of fibrinogen degradation, number of fibrin cross-links, and levels of factor XIII and plasminogen were the same for both group. There were significant reductions in antithrombin activity, the euglobulin lysis time, and fibrinolytic inhibitor level in women using oral contraceptives. An estrogen dose effect was suggested for fibrinogen concentration and the degree of antithrombin activity. The increased fibrinolytic activity and decreased fibrinolytic inhibitor levels are consistent with in vitro observations that antithrombin also inhibits plasmin activity. Thus while oral contraceptive-induced depression of antithrombin III could possibly predispose to thrombosis by diminishing the inhibition of the serine protease clotting factors, the concomitant decreased level of plasmin inhibition might balance the system by favoring thrombolysis as well as the digestion and inactivation of certain clotting factors by plasmin.
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PMID:Fibrin formation and dissolution in women receiving oral contraceptive drugs. 84 77

The crystallographic structure of the plasminogen kringle 4-epsilon-aminocaproic acid (ACA) complex (K4-ACA) has been solved by molecular replacement rotation-translation methods utilizing the refined apo-K4 structure as a search model (Mulichak et al., 1991), and it has been refined to an R value of 0.148 at 2.25-A resolution. The K4-ACA structure consists of two interkringle residues, the kringle along with the ACA ligand, and 106 water molecules. The lysine-binding site has been confirmed to be a relatively open and shallow depression, lined by aromatic rings of Trp62, Phe64, and Trp72, which provide a highly nonpolar environment between doubly charged anionic and cationic centers formed by Asp55/Asp57 and Lys35/Arg71. A zwitterionic ACA ligand molecule is held by hydrogen-bonded ion pair interactions and van der Waals contacts between the charged centers. The lysine-binding site of apo-K4 and K4-ACA have been compared: the rms differences in main-chain and side-chain positions are 0.25 and 0.69 A, respectively, both practically within error of the determinations. The largest deviations in the binding site are due to different crystal packing interactions. Thus, the lysine-binding site appears to be preformed, and lysine binding does not require conformational changes of the host. The results of NMR studies of lysine binding with K4 are correlated with the structure of K4-ACA and agree well.
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PMID:The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4. 165 49

A study was made of blood coagulation, physiological anticoagulants and fibrinolysis in 120 elderly patients with cerebrovascular diseases, including 50 subjects in the acute period of ischemic brain stroke. To estimate activation of the fibrinolytic system, the levels of plasminogen and free plasmin were measured. Phasic changes in the system of blood coagulation were detected, variants of antithrombin III depression were delineated, and a relationship was established between the activity of enzymes of the fibrinolytic system and the site of an ischemic focus in the brain. Five coagulopathic syndromes of the acute period of brain stroke were distinguished, the principles of their differentiated treatment were based.
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PMID:[Diagnosis and treatment of coagulopathic syndromes in ischemic stroke]. 166 74

Treatment of coronary thrombosis with thrombolytic agents was first introduced in the 1950s. Clinical trials, primarily with streptokinase during the 1960s and 1970s, addressed the effects of thrombolysis on mortality rates after acute myocardial infarction, but were inconclusive and largely ignored. In 1976, Chazov et al. from the Soviet Union demonstrated that intracoronary streptokinase could produce prompt recanalization of a totally occluded infarct-related artery. In 1980, DeWood et al. demonstrated that 87% of patients with classic Q-wave myocardial infarction had total occlusion from coronary thrombosis of the infarct-related artery when studied during the first 4 hours of their infarction and that 65% of these arteries were still occluded when patients were studied between 12 and 24 hours after infarction. These observations stimulated renewed interest in thrombolytic therapy for acute myocardial infarction. Mortality trials have subsequently demonstrated that agents such as recombinant tissue plasminogen activator, streptokinase, and anisoylated plasminogen streptokinase activator complex remarkably reduce early mortality rates among patients with acute myocardial infarction when treatment is instituted within the first 6 hours of infarction. Benefit has yet to be demonstrated, however, in patients with acute myocardial infarction characterized by ST-segment depression. This whole area is currently under study by the TIMI investigators. TIMI-3B is a mortality study in which patients with either non-Q-wave myocardial infarction or unstable angina with rest pain are randomly assigned to receive either tissue plasminogen activator or placebo. Results of this trial will help us in the future to determine the appropriate role of thrombolytic therapy in treating acute ischemic syndromes other than transmural myocardial infarction.
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PMID:Overview: rationale of thrombolysis in treating acute myocardial infarction. 189 38

In a randomized placebo-controlled study, seven patients with acute myocardial infarction allocated to intravenous treatment with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) and seven patients allocated to placebo were studied during eight sampling periods before and after treatment. Seven patients with acute myocardial infarction treated intravenously with 1.5 million U of streptokinase were later studied during two sampling periods before and after treatment. The placebo group showed no significant deviations of endogenous factor XII-dependent fibrinolytic activity (p greater than 0.05). In the rt-PA group, this activity decreased significantly (p less than 0.001) after the infusion and remained depressed throughout the 1st 4 days. A significant decrease in activity (p less than 0.05) was also found in the streptokinase-treated patients. The depletion of factor XII-dependent fibrinolytic activity was not due to generation of inhibition or a depletion of factor XII, prekallikrein and plasminogen, but could be related to the proactivator of this system. It is concluded that rt-PA (and streptokinase) treatment in patients with acute myocardial infarction causes a prolonged depletion of factor XII-dependent fibrinolytic activity. This depression of endogenous fibrinolytic activity needs to be evaluated in relation to the enhanced risk of coronary reocclusion after thrombolytic therapy.
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PMID:Long-lasting depression of the factor XII-dependent fibrinolytic system in patients with myocardial infarction undergoing thrombolytic therapy with recombinant tissue-type plasminogen activator: a randomized placebo-controlled study. 140 37

The results of several major trials of i.v. thrombolysis in patients with acute myocardial infarction have demonstrated the efficacy of the treatment in reducing mortality. Streptokinase and rt-PA have been shown to be effective (APSAC = anisoylated plasminogen streptokinase activator complex; GISSI = Gruppo Italiano per lo Studio della Streptochinasi nell' Infarto miocardico, ASSET = Anglo Scandinavian study of early thrombolysis, rt-PA). This treatment is associated with the potential for cerebral and major bleeding, especially in elderly patients. The benefit of this treatment in patients with cardiogenic shock or hypotension (ISIS-2) is discussed. There is no convincing evidence that patients with ST-segment depression or those with an equivocal electrocardiogram had been benefited from i.v. thrombolysis. Further studies with i.v. thrombolysis and/or other strategies need to be explored. Overall the use of i.v. thrombolytic agents in combination with PTCA in patients with acute myocardial infarction have resulted in improvement in ventricular function and survival in patients eligible for this therapy. However, new techniques and therapeutic approaches to prevent reocclusion, to prevent reperfusion injury, to prevent restenosis after PTCA, to prevent atherosclerosis in the infarct and non-infarct related arteries, and to reduce the potential for ventricular arrhythmias and sudden death as well as the potential for mural thrombi and embolization after infarction are needed. The 1990's will see attempts to determine the optimum adjunctive therapy or "cocktail" of agents to be used with i.v. thrombolysis.
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PMID:Thrombolysis in acute myocardial infarction: need for a change in strategy and future directions. 212 41

The fibrinolytic potential of the vasculature is modulated primarily by the availability and activity of plasminogen activators, which convert the zymogen plasminogen into the active fibrin-degrading enzyme plasmin. The activities of these key regulatory enzymes are directly neutralized by their primary endogenous inhibitor, plasminogen activator inhibitor-1 (PAI-1). Although some individuals with a tendency to develop thrombotic disorders exhibit elevated levels of PAI-1 in their plasma, the cause-and-effect relationship between increased PAI-1 and thrombosis is still unclear. Specifically, it is not known whether chronic depression of fibrinolytic activity results in the development of thrombosis. To address this question we developed transgenic mice in which the contribution of PAI-1 to thrombus formation could be evaluated. The results presented in this report indicate that elevated levels of PAI-1 contribute to the development of venous but not arterial occlusions.
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PMID:Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene. 236 66

Significance of fibrinolysis in pathophysiology of progressive systemic sclerosis (PSS) has been the subject of much speculation. Renal disease in PSS was associated with significant depression of an inhibitor of fibrinolysis, antithrombin III (ATIII), independent of general disease activity. Association of ATIII depression with plasminogen consumption supports an active role for plasmin or another ATIII-inhibitable enzyme in the pathophysiology of renal disease in PSS, and may explain the thrombotic tendency and propensity for fibrin deposition.
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PMID:Perturbation of fibrinolysis inhibitors in progressive systemic sclerosis. 258 28

Disturbances of blood coagulation were studied in 32 consecutive patients with typhoid fever on their admission to hospital. Estimations of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products (FDPs), factors VII, VIII and XII, alpha I antitrypsin, plasminogen, CI esterase inhibitor, and platelet counts were performed as well as liver function tests and blood counts. Five patients had laboratory evidence of disseminated intravascular coagulation (DIC) and two had a generalised bleeding disorder which in the other three was inapparent. The platelet count in the group as a whole was low (P less than 0.05) and the FDPs in most cases were mildly elevated. The pre-kallikrein values were depressed in three of the five with DIC, whereas factor XII was not reduced. These results indicate that bleeding disorders in typhoid fever are uncommon. The depression of pre-kallikrein indicates that the DIC is probably triggered by activation of the intrinsic coagulation pathway. Most patients had lymphopenia and monocytopenia but only two had neutropenia.
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PMID:Disturbances of blood coagulation associated with Salmonella typhi infections. 335 16

An analysis was made of 41 cases of disseminated intravascular coagulation in dogs, with the objective of evaluating routine and nonroutine laboratory tests used in making the diagnosis. The dogs were grouped on the basis of underlying disease, which included neoplasia (39%), pancreatitis (30%), chronic active hepatitis (15%), heat stroke (12%), and sepsis (4%). Of the diagnostic tests evaluated, those for determination of activated partial thromboplastin time, antithrombin III activity, prothrombin time, and the platelet count were the most valuable. Of the clotting factors, factor V activity was decreased more frequently than the activity of factor VIII:C (factor VIII: procoagulant). The factor VIII:C activity was in conflict with prevailing dogma that reflects depression of this factor in disseminated intravascular coagulation. Factor VIII:C activity was decreased in only 29% of dogs studied. Activation of the fibrinolytic system was manifested by decreased plasminogen activity in 49% of the dogs studied. Sixty-one percent of the dogs had increased amounts of fibrin (ogen) degradation products.
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PMID:Disseminated intravascular coagulation: antithrombin, plasminogen, and coagulation abnormalities in 41 dogs. 726 67


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