Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In washed platelets both from DOCA-salt and renal hypertensive rats, there was a marked decrease in thrombin-induced aggregation and secretion responses compared with those of respective controls. Concomitantly, the platelets showed attenuated malondialdehyde (MDA) formation and reduced serotonin contents, suggesting the presence of degranulated platelets in the circulation due to hypertension. In platelets from stroke-prone spontaneously hypertensive rats (SHRSP) at early hypertensive stages, thrombin-induced aggregation and secretion responses were similarly reduced. However, the platelet hypofunctions did not accompany reduced MDA formation and serotonin contents. Properties of platelets obtained from SHRSP at late hypertensive stages resembled those of platelets from experimentally hypertensive rats. These results suggest that the mechanisms of platelet hypofunction differ between experimental hypertension and spontaneous hypertension in their early stages. The hypo-aggregability observed in experimental hypertension appears to be secondary to the hypertension, whereas that seen in spontaneous hypertension seems to be a primary defect and not secondary to hypertension at early stages of hypertension.
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PMID:Changes in platelet function due to hypertension: comparison of experimental hypertension with spontaneous hypertension in rats. 270 9

To assess the time course of thrombosis and fibrinolysis after acute stroke, we measured concentrations of fibrinopeptide A (FpA), B-beta 1-42 peptide (B-beta 1-42), B-beta 15-42 peptide (B-beta 15-42), and crosslinked D-dimer (XDP) in 31 patients at varying times following acute ischemic stroke and in 13 neurologically stable patients with chronic strokes. FpA levels were markedly elevated during the first week after stroke and declined slowly during the first month. Mean FpA levels were not significantly elevated in chronic stroke patients. Mean XDP levels were slightly elevated during the first week and increased during the next 2 weeks after stroke. B-beta 1-42 and B-beta 15-42 levels were not elevated at any time following acute stroke. Our data suggest that fibrin formation greatly exceeds endogenous fibrinolysis during the acute phase of ischemic stroke. Endogenous fibrinolysis develops slowly following stroke. Prolonged elevation of FpA concentration suggests that thrombin activity and fibrin formation continue for up to 4 weeks in some patients with ischemic stroke.
Stroke 1989 May
PMID:Hemostatic markers in acute stroke. 271 98

Anti-thrombin III is the major inhibitor of activated blood clotting factors. We studied 320 patients with climacteric symptoms who received estrogen replacement therapy to assess the effect of hormone therapy on Anti-thrombin III (AT-III) activity). Of the 320 patients 80 patients received Prempak C (0.625 mg) for 2 years, 82 patients received Prempak C (1.25 mg) for 2 years, 78 patients received Cycloprogynova (1 mg) for 2 years and the remaining 80 patients received Cycloprogynova (2 mg) for 2 years. The mean AT-III activity before, during and 3 months after treatment showed no significant difference in all the four groups of patients. There was no incidence of myocardial infarction or stroke or thrombo-embolic disease in this group of 320 patients receiving estrogen replacement therapy.
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PMID:Effect of hormone replacement therapy on anti-thrombin III activity in post menopausal women. 287 74

PAF-acether, a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms of action of PAF are largely unknown. We have found that the psychotropic triazolobenzodiazepine drugs, alprazolam and triazolam, potently (IC50 less than 1 microM) inhibit PAF-induced shape change, aggregation and secretion of human platelets. These effects are specific for PAF-activation, since the responses of human platelets to other agonists (ADP, thrombin, epinephrine, collagen, arachidonate and the Ca++ ionophore, A23187) are not inhibited by these triazolobenzodiazepines. The action of triazolobenzodiazepines on PAF-induced platelet function has clinical relevance, especially in diseases where enhanced platelet aggregability may lead to thrombosis and atherosclerosis. In addition, the ability of triazolobenzodiazepines to inhibit other PAF-mediated cellular-responses, such as anaphylactic shock or bronchoconstriction, suggests that these drugs may be useful in preventing several known pathophysiological effects of PAF. The specific antagonism of PAF action by psychotropic drugs also suggests that PAF or PAF-like phospholipids may play a role in neuronal function. This possibility was tested by examining the effects of PAF on neural cells of the clonal line NG108-15, grown in culture in a chemically defined, serum-free medium. Low concentrations of PAF (0.5-2.5 microM) induced neurite extension in NG108-15 cells, whereas higher concentrations (greater than 3 microM) were cytotoxic. Using NG108-15 cells preloaded with aequorin, it was found that PAF causes an increase in intracellular ionized calcium concentration, which is dependent on the presence of extracellular calcium. These results suggest that PAF-induced Ca++ uptake may play a role in neuronal development, and that circulating PAF may contribute to the neuronal degeneration caused by the exposure of neural tissues to blood in situations such as spinal cord injury, trauma, or stroke.
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PMID:Interactions of the alkyl-ether-phospholipid, platelet activating factor (PAF) with platelets, neural cells, and the psychotropic drugs triazolobenzodiazepines. 289 25

The stainless steel cannula inserting method was used to investigate the blocking effects of nimodipine on vascular responses to intraluminal administration of 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) before and after application of abluminal blood containing thrombin in isolated and perfused canine basilar arteries. A transient elevation of perfusion pressure was observed initially, and during the course of the experiment the perfusion pressure gradually increased. Nimodipine significantly depressed both transient and prolonged changes of perfusion pressure. Dose-dependent vasoconstriction induced by 5-HT was significantly enhanced, while that evoked by KCl was significantly attenuated for up to 8 hours after the application of blood. Pretreatment with nimodipine inhibited vasoconstriction to 5-HT less effectively than to KCl both before and after application of blood. The proportion of the 5-HT-induced vasoconstriction, which was sensitive to nimodipine, was reduced after application of blood, while no such change was observed in the responses to KCl. It is suggested that the augmentation of cerebrovascular responses to 5-HT in the early stage of subarachnoid hemorrhage may be mediated mainly by changes in intracellular calcium utilization rather than by the increase of calcium influx through nimodipine-sensitive channels.
Stroke 1989 Jan
PMID:Effect of nimodipine on canine cerebrovascular responses to 5-hydroxytryptamine and potassium chloride after exposure to blood. 291 23

Platelet function and thrombin activity were investigated in 12 hospitalized patients (7 men and 5 women, mean age 53 years) who had had transient cerebral ischemic attacks in the previous 2-12 weeks. Each patient was given an extensive clinical and instrumental evaluation, including Doppler sonography of the cervical and lower limb vessels, cerebral angiography, and head computed tomography scan, after which relevant atherosclerotic disease was excluded. The controls consisted of 12 subjects hospitalized for nonvascular neurologic problems and matched for age, sex, and risk factors to the transient ischemic attack patients. Collagen-induced platelet thromboxane B2 production, plasma beta-thromboglobulin, and fibrinopeptide A were significantly higher in the patients than the controls. Platelet aggregability by collagen was the same in the 2 groups. Platelet hyperfunction and enhanced thrombin activity are present in patients some weeks after the acute episode, suggesting that the hemostatic system has a primary pathogenetic role.
Stroke
PMID:Platelet function and thrombin activity in patients with recent cerebral transient ischemic attacks. 295 21

The hemodynamic effects of blood volume augmentation and mechanical ventilation (MV) with positive end-expiratory pressure (PEEP) were studied in nine Beagles anesthetized with halothane before and after thrombin-induced pulmonary hypertension. The effect of therapy with dopamine, norepinephrine with and without nitroglycerin (NTG), and intraaortic balloon pumping (IABP) were studied in a second series of six Beagles. Before thrombin, dextran (35 ml.kg-1) caused a significant increase in right and left ventricular end-diastolic and end-systolic volumes (RV and LVEDV, and RV and LVESV). However, RV and LV performance, as estimated by ejection fraction, was unchanged during volume loading and MV with PEEP when the pulmonary vasculature was intact. The response to volume loading and MV with PEEP was altered significantly once PVR had been increased with the administration of thrombin. Stroke volumes were decreased, and remained so, despite volume loading and MV with PEEP. LVEDV decreased without a decrease in LVEDP, indicating a decreased LV compliance. Dopamine and norepinephrine with and without NTG increased stroke volumes and RV ejection fraction in contrast to IABP. Assessment of LV performance, according to the Frank-Starling mechanism, requires a measure of end-diastolic volume when diffuse pulmonary vasoconstriction leads to RV distension and LV hypovolemia secondary to septal shift. Measurement of LV filling pressures can provide misleading values to estimate changes in LV volume in this setting. Measurement of ventricular volumes is required for optimal management of patients with severe acute respiratory failure and pulmonary hypertension.
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PMID:Cardiovascular adjustments to pulmonary vascular injury in dogs. 312 66

We measured cytoplasmic ionized calcium concentrations [( Cai2+]) in aequorin-loaded gel-filtered platelets from 38 patients with acute occlusive stroke (12 treated with aspirin, 26 untreated) and 25 healthy controls. Compared with controls, baseline [Cai2+] was higher in untreated patients (p less than 0.002), maximal 36-72 hours after the onset of neurologic dysfunction (p less than 0.0001), in those patients with as well as those without major stroke risk factors. The increase in [Cai2+] after stimulation with 0.5 and 1.0 unit/ml thrombin (p less than 0.05), 2 and 4 micrograms/ml collagen (p less than 0.02), and 0.5 and 1.0 mM platelet activating factor (p less than 0.05) were also greater in untreated patients, but the profiles of these changes were parallel to those in controls. Even though the platelets of stroke patients are more sensitive to activation, they are functionally similar to those of controls. Aspirin treatment reduced baseline [Cai2+] as well as thrombin- and collagen-induced [Cai2+] changes. Platelet activating factor-induced increase in [Cai2+] was not altered by aspirin treatment. Our results suggest that the usefulness of aspirin in stroke is limited because aspirin does not suppress platelet responsiveness to all in vivo thrombogenic stimuli. Specific platelet activating factor antagonists may prove to be useful therapeutic agents in stroke.
Stroke 1988 Oct
PMID:Baseline and activated platelet cytoplasmic ionized calcium in acute ischemic stroke. Effect of aspirin. 317 82

Endothelium-dependent relaxations are reduced in hypertensive rats. High dietary potassium supplementation reduces the incidence of strokes in Dahl rats independently of blood pressure, thereby suggesting a direct protective effect of the diet. Endothelium-dependent relaxations and aortic vascular architecture were studied in Dahl salt-sensitive rats fed 8% NaCl, 0.1% NaCl, or 8% NaCl plus 3.6% potassium citrate for 8 weeks. Rats fed 8% NaCl or 8% NaCl plus 3.6% potassium citrate became hypertensive, while those fed 0.1% NaCl did not. Aortic rings with and without endothelium were suspended in organ chambers filled with physiological salt solution (37 degrees C) and aerated with 95% O2, 5% CO2. In rings contracted with norepinephrine, acetylcholine and adenosine 5'-diphosphate caused endothelium-dependent relaxations that were significantly reduced in rats fed 8% NaCl as compared with those fed 0.1% NaCl. Potassium supplementation (8% NaCl/3.6% potassium citrate) significantly enhanced relaxations to acetylcholine in salt-sensitive rats, while those to adenosine 5'-diphosphate and thrombin were either minimally affected or unchanged. Relaxations to sodium nitroprusside were similar in rats with or without potassium supplementation. Hypertension significantly increased aortic medial and intimal thickness. Dietary potassium had no significant effect on the vascular architecture. These results suggest that high potassium diet enhances endothelium-dependent relaxations in Dahl rats at least in part independently of changes in blood pressure. Thus, potassium may be important for its protective effect against stroke and renal damage in this animal model of hypertension.
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PMID:High potassium diet augments endothelium-dependent relaxations in the Dahl rat. 326 44

Thrombogenesis is increasingly recognised as an immediate cause of most major clinical episodes of ischaemic heart disease (IHD) and the haemostatic system makes a significant contribution to the development of atheroma. It is therefore important to consider how far concepts of increased thrombotic tendency and hypercoagulability can be demonstrated in reality. A number of general observations do suggest that characteristics of the circulating blood influence the course of events in IHD--for example, the occurrence of IHD or stroke in young women using oral contraceptives in whom advanced arterial wall changes are not a feature. Epidemiologically, the coagulation system has been more rewarding than the study of platelets. The Northwick Park Heart Study (NPHS) has demonstrated a strong relationship between the level of factor VII activity and the later incidence of IHD. Several biochemical characteristics of factor VII suggest that this relationship may well be one of cause and effect. There is growing evidence that high levels of factor VII activity lead to high levels of thrombin production. In addition to NPHS, three other prospective studies have shown an association between high levels of plasma fibrinogen and IHD incidence. Again, there are several reasons for believing that this association, too, is of pathogenetic significance. Dietary fat intake is a major determinant of the factor VII activity level, and smoking of the fibrinogen level. Hypercoagulability determining IHD is best defined, on present evidence, as over-activity of procoagulatory influences (whereas hypercoagulability leading to venous thrombosis is predominantly manifested as underactivity of natural defence mechanisms).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypercoagulability and ischaemic heart disease. 333 83


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