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 epithelial lining of the airways is subject to injury through several processes, including infections, bronchiolitis, and fume exposures. Because airway fibrin deposition influences the course of local injury, we examined how two inflammatory cytokines influenced fibrin formation and clearance in human tracheal epithelial cells (TEC). TEC were treated with transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). TNF-alpha increased release of tissue factor (TF)-related procoagulant activity that, through generation of factor Xa, promotes assembly of the prothrombinase complex at the cell surface. Fibrinolytic activity was plasminogen dependent and due to both urokinase (uPA) and tissue plasminogen activator (tPA). The cells expressed plasminogen activator inhibitor 1 (PAI-1), but relatively little PAI-2. Depression of fibrinolysis by TGF-beta correlated with increased PAI-1. Conversely, TNF-alpha increased plasminogen activator (PA) activity due to increased uPA. Fibrinolytic activity was inhibited by actinomycin D and cyclohexamide, but changes in mRNAs for uPA, tPA, PAI-1, and TF by either cytokine were not appreciable. PAI-2 mRNA was not found. The data indicate that TGF-beta decreases the fibrinolytic capacity of TEC, suggesting that this cytokine promotes fibrin retention. TNF-alpha increases expression of both procoagulant and fibrinolytic activities; this differential regulation could favor both pericellular fibrin formation and dissolution.
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PMID:Effects of TGF-beta and TNF-alpha on procoagulant and fibrinolytic pathways of human tracheal epithelial cells. 781 Jun 74

Data obtained in experiments in 80 rats and in clinical observations of 24 patients with burns of the II and IIIA degrees showed the activation of vasculo-thrombocytic and procoagulant links of the hemostasis system with a simultaneous depression of the anticoagulative blood system. The thermal trauma is followed by a dramatic decrease of the concentration of heparin, fibrinogen, decreased activity of antithrombin-III, fibrinolysis and plasminogen activators. There was a simultaneous growth of concentration of antiplasmins (alpha 2-macroglobulin and alpha 1-antitrypsin).
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PMID:[The blood coagulating activity in burns]. 875 66

Insulin-like growth factor-binding proteins (IGFBPs) modulate IGF action at cellular level, through either inhibition or potentiation, and they also have intrinsic activity that is independent of their binding to IGFs. In prostate carcinoma (PC-3) cells, which are capable of growth for several days in serum-free medium, non-glycosylated recombinant human IGFBP-3 (rhIGFBP-3) had a biphasic mitogenic effect, stimulation being dose-dependent up to 20 ng/ml, followed by progressive depression down to zero stimulation at 150-200 ng/ml. This mitogenic effect was not intrinsic activity, but involved IGF-II secreted by the cells, since stimulation was abolished in the presence of anti-type 1 IGF receptor antibody (alpha IR-3). Western ligand- and immunoblot analysis of the culture media revealed several IGFBP species, in particular IGFBP-3 which exhibited an electrophoretic profile characteristic of limited proteolysis. The amounts of the proteolytic fragments increased in parallel with the concentrations of added rhIGFBP-3, but a large amount of intact protein remained at the highest concentrations added. When a serine protease inhibitor, 4-(2-aminoethyl)-benzenesulphonyl fluoride (Pefabloc SC), was added at concentrations demonstrated to be non-toxic to the cells, IGFBP-3 proteolysis was diminished and rhIGFBP-3-induced stimulation of proliferation was suppressed. Conversely, in the presence of plasminogen transformed to plasmin by urokinase secreted by the cells, proliferation stimulated by rhIGFBP-3 and its proteolysis were enhanced. Our results suggest that the biphasic mitogenic effect of rhIGFBP-3 on PC-3 cells reflects changes in the availability to the cells of the IGF-II they secrete. This availability depends on the extent of IGFBP-3 proteolysis (which promotes release of bound IGF-II) and on the proportion of intact forms (which sequestrate secreted IGF-II).
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PMID:Recombinant human insulin-like growth factor (IGF) binding protein-3 stimulates prostate carcinoma cell proliferation via an IGF-dependent mechanism. Role of serine proteases. 889 45

Elevated plasma levels of lipoprotein(a) [LP(a)] are associated with increased an risk of developing atherosclerosis. This increased risk may be due to an Lp(a)-mediated depression of fibrinolytic activity. Lp(a) regulates fibrinolysis by controlling the activity of plasminogen activators. Lp(a) is a low density lipoprotein with an apoprotein(a) subunit which has a high degree of homology with the fibrinolytic zymogen plasminogen. The apoprotein(a) subunit contains up to thirty seven copies of a domain homologous to the plasminogen kringle 4 domain, which enables Lp(a) to bind to fibrin. The subunit also has a zymogen domain, but it is not activated by plasminogen activators. Lp(a) inhibits plasminogen activation by competing with plasminogen for access to plasminogen activators bound to vascular surfaces. Lp(a) also competes with the irreversible inhibitor of plasminogen activators, plasminogen activator inhibitor-1. Therefore increases in Lp(a) concentration may decrease fibrinolytic activity by preventing activation of plasminogen, but Lp(a) may also prolong plasminogen activation by preventing the irreversible inhibition of the activators. At elevated levels of Lp(a) the decreased rate of plasmin generation may not be offset by the prolongation in plasminogen activation, and fibrinolysis will be inhibited.
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PMID:Lipoprotein (a) in the regulation of fibrinolysis. 922 22

The pathophysiological basis of hemorrhage in dengue infections remains poorly understood, despite the increasing global importance of these infections. A large prospective study of 167 Vietnamese children with dengue shock syndrome documented only minor prolongations of prothrombin and partial thromboplastin times but moderate to severe depression of plasma fibrinogen concentrations. A detailed study of 48 children revealed low plasma concentrations of the anticoagulant proteins C, S, and antithrombin III, which decreased with increasing severity of shock, probably because of capillary leakage. Concurrent increases in the levels of thrombomodulin, tissue factor, and plasminogen activator inhibitor type 1 (PAI-1) indicated increased production of these proteins. Thrombomodulin levels suggestive of endothelial activation correlated with increasing shock severity, whereas PAI-1 levels correlated with bleeding severity. Dengue virus can directly activate plasminogen in vitro. Rather than causing true disseminated intravascular coagulation, dengue infection may activate fibrinolysis primarily, degrading fibrinogen directly and prompting secondary activation of procoagulant homeostatic mechanisms.
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PMID:Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome. 1211 93

This is the case report of a 44-year-old woman presented with an acute stroke immediately after electroconvulsive therapy (ECT). The patient had no significant medical history other than chronic depression. She was taking sertraline, and she had had multiple previous ECT treatments without any complications. While being monitored in the recovery room within 10 minutes after the last ECT session, she was found to have sudden onset of left-sided flaccid hemiplegia and numbness along with slurred speech. On arrival to our hospital, she was found to have flaccid hemiplegia on the left side involving the face, arm, and leg (face and arm more than the leg involvement), severe dysarthria, and mild neglect syndrome (National Health Institute Stroke Scale of 14). Noncontrast computed tomography (CT) of the head showed no signs of early ischemia, and iodine contrast CT angiography revealed right middle cerebral artery (MCA) (distal M1 segment) clot. Patient received intravenous recombinant tissue plasminogen (rt-PA) at 2.5 hours after the onset of symptoms, and then a total of 3.0 mg of intra-arterial (IA) rt-PA. Angiography at the end of the procedure showed successful recanalization of the M1 segment and normal vessel caliber with adequate distal flow. After the procedure, the patient made rapid improvements in all of her initial symptoms during the first 24 hours. An extensive stroke workup failed to reveal any cause of the stroke, including usual stroke and hypercoagulable risk factors. This was an acute embolic stroke immediately following an ECT, and without the aggressive thrombolytic therapy, the patient's outcome would have been poor because there was an M1 segment clot with a major MCA syndrome with relatively high National Institute of Health Stroke Scale. The neurological side effect profile of ECT is reported to be minimal with most common symptoms being headache, disorientation, and memory complaints. There is no clear cause-and-effect relationship in this case, and the stroke after ECT is extremely rare. In such rare event of stroke while receiving ECT, there is an effective treatment available using both intravenous and IA thrombolysis as reported in this case.
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PMID:Acute embolic stroke after electroconvulsive therapy. 1663 11

Major depressive disorder (MDD) is a common disabling psychiatric illness with an unknown etiology. Evidence from animal and human studies suggests that a disturbance in serotonergic (5-HT) activity and/or brain-derived neurotrophic factor (BDNF) signaling may be implicated in the pathogenesis of MDD. Recently, a protein, p11, has been found to increase the number of 5-HT(1B) receptors on the surface of cells and enhance 5-HT(1B) receptor function. Furthermore, mice over-expressing p11 acted as if they were undergoing treatment with antidepressants and p11 knockout mice exhibit a depression-like phenotype and reduced behavioural reactions to an antidepressant. As tissue-type plasminogen activator (tPA)/plasminogen proteolytic cascade is implicated in the cleavage of proBDNF to BDNF, and p11, a component of the Annexin II, which can greatly enhance the activation of plasmin by tPA, it is proposed that p11 may act through the tPA/plasminogen/BDNF pathway to achieve its antidepressant effect. Attempts to confirm this hypothesis may lead to new directions in the study of the pathogenesis of MDD and the development of a novel intervention for this disorder. In addition, BDNF is also implicated in several psychiatric diseases such as schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder and Alzheimer's disease; whether p11 and other components related to the tPA/plasminogen pathway may be related to the pathogenesis of these diseases needs further exploration.
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PMID:The P11, tPA/plasminogen system and brain-derived neurotrophic factor: Implications for the pathogenesis of major depression and the therapeutic mechanism of antidepressants. 1689 Mar 84

The family of hydroxymethylglutaryl coenzyme A reductase inhibitors, collectively known as statins, are used clinically to reduce plasma cholesterol levels. Recent reports indicate that statin therapy is associated with a reduced risk of depression, although the mechanism underlying this antidepressant effect is unknown. Evidence suggests that increasing central BDNF activity plays an important role in the treatment of major depression. In the nervous system, the proteolytic cleavage of pro-BDNF, a BDNF precursor, to BDNF through the tissue-type plasminogen activator (tPA)-plasmin pathway represents one mechanism that can regulate the action of BDNF. In vitro studies have demonstrated that statins can induce tPA and inhibit plasminogen activator inhibitor-1, the major inhibitor of tPA. It is therefore possible that statins could act through the tPA-plasminogen pathway to increase BDNF and achieve an antidepressant effect. It is suggested that statins could be of therapeutic potential for patients with major depression: especially those that have an abnormality in the tPA-plasminogen pathway or comorbidities relating to cardiovascular disease. Furthermore, BDNF dysfunction has also been implicated in several other neuropsychiatric diseases, such as Alzheimer's disease, attention-deficit hyperactivity disorder and Rett syndrome. The potential use of statins in these diseases may warrant further exploration.
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PMID:Statins may enhance the proteolytic cleavage of proBDNF: implications for the treatment of depression. 1735 Jul 66

Epidemiological, genetic and clinical studies have demonstrated an association between major depressive disorder (MDD) and cardiovascular disease (CVD). For example, MDD is a risk factor for the development of CVD, while around one fifth of patients with CVD have MDD and a significantly larger percentage have subsyndromal symptoms of depression. Furthermore, patients with CVD and depression have an increased risk of future cardiac events compared to similar cohorts without depression, independent of baseline cardiac dysfunction. Despite evidence that CVD and MDD are epidemiologically linked, the cause of this correlation is still unknown. Several risk factors including physical and psychological stress, smoking, physical inactivity and inflammation have been proposed to mediate the interaction between MDD and CVD. The tissue-type plasminogen activator (tPA)-plasminogen proteolytic cascade is widely expressed in the brain. Accumulating evidence from preclinical and clinical studies suggests that tPA and its inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. In addition, brain-derived neurotrophic factor (BDNF) is important for the pathogenesis of MDD and the tPA-plasminogen proteolytic cascade has been implicated in the cleavage of proBDNF to BDNF in the brain, by which the direction of BDNF action is controlled. Thus, it is proposed that tPA-plasmin pathway dysfunction may play a role in the link between MDD and CVD. Future study of the components in the tPA-plasminogen system in CVD patients comorbid with MDD may lead to new, potentially important insights into the link between MDD and CVD, and might also contribute to novel strategies for the management of these two common and devastating diseases.
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PMID:Is dysfunction of the tissue plasminogen activator (tPA)-plasmin pathway a link between major depression and cardiovascular disease? 1892 45

Disturbed alveolar fibrin turnover is intrinsic to acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pneumonia and is important to its pathogenesis. Recent studies also suggest disturbed alveolar fibrin turnover to be a feature of ventilator-induced lung injury (VILI). The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors, and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. Administration of anticoagulant agents (including activated protein C, antithrombin, tissue factor-factor VIIa pathway inhibitors, and heparin) and profibrinolytic agents (including plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ALI/ARDS and pneumonia. In this article, we review the involvement of coagulation and fibrinolysis in the pathogenesis of ALI/ARDS pneumonia and VILI and the potential of anticoagulant and profibrinolytic strategies to reverse pulmonary coagulopathy and pulmonary inflammatory responses.
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PMID:The role of bronchoalveolar hemostasis in the pathogenesis of acute lung injury. 1895 88


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