Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After a thorough study, and having chosen the machine that is to equip an average sized haemostasis laboratory, the installation then requires certain steps (the reorganisation of work, better adapted reagents, a change of normality, a fine tuning of the technics, the time to get used to the machine). In this perspective, this work describes the regulation of the technic to determine the heparin activity on the Fibrintimer 10 (F 10) by chronometry (thrombin clotting time with variable concentration), a study of the repeatability and reproducibility of activated partial thromboplastin time (APTT), plasma heparin (HEP) and fibrinogen on the Fibrintimer 10, a study of the correlation between the results we got with the F 10 and the thermostat water-bath for the APTT and the HEP and between those we got on the F 10 and the fibrometer for the fibrinogen. The F 10 has allowed us to save more time whilst keeping the same technics and reagents. The determination of the heparin activity, by thrombin clotting time with variable concentration, gives us a method which is quick, cheap and useful for the following-up of the patients undergoing a treatment with standard heparin. The reproducibility and repeatability prove to be good for the 3 tests in our operatory conditions as well as the correlations between the results we get with both methods.
...
PMID:[Activated thromboplastin time, plasma heparin and plasma fibrinogen using the Fibrintimer 10]. 321 91

The effects of fibrin microembolism were examined using an infusion of a prothrombin activator (Echis carinatus venom, ECV; 30 min, 0.5 NIH thrombin equivalent units/kg) in acute mongrel dogs prepared with a pulmonary lymph cannula (n = 6, 12.3-21.5 kg). Lymph flow increased approximately 2.5-fold after 1-1.5 hr of elevated left atrial pressure (Pla = 20 cm H2O; 26 +/- 7 to 63 +/- 16 microliter/min, P less than 0.01) and the plasma to lymph protein concentration ratio (CP/CL) declined from 0.66 +/- .04 to 0.54 +/- .16 (P less than 0.01, x +/- SE). After Pla was reduced to control levels, the initiation of fibrin microembolism was associated with an approximate 2.7-fold elevation of lymph flow (62 +/- 8 microliters/min, P less than 0.01) and the CP/CL was not changed (0.56 +/- 0.04, P = ns). When Pla was increased following microembolism, lymph flow more than doubled to 117 +/- 24 microliter/min (P less than 0.01) and the CP/CL remained unaltered (0.56 +/- 0.03, P = ns). These changes were associated with afibrinogenemia and the appearance of fibrin degradation products (FDP) in plasma (150 +/- 50 micrograms/ml) and lymph (80 micrograms/ml) in three of the animals tested. No consistent pattern was seen in the CL/CP of separate endogenous plasma proteins after each intervention. These data support the view that pulmonary fibrin microembolism without inhibition of the fibrinolytic system was associated with an early increased pulmonary microvascular permeability to protein. In a separate group of similarly prepared animals (n = 8, 13-21.5 kg) without a lymph catheter, scanning electron microscopic observations showed branching fibrin microemboli to partially occlude some pulmonary arterioles. Mixed thrombus formations in larger precapillary blood vessels were also seen. Ultrastructural observations revealed the deposition of fibrin strands (periodicity = 220-230 A) within the pulmonary capillaries. Some of these deposits were overlaid by lamellar pseudopodia from endothelial cells and the fibrin appeared to be within these cells. Although plasmalemmal vesicles seemed to be more numerous in the endothelial cells with adjacent fibrin deposits, no gaps or breaks were seen in the densely stained interendothelial cell junctions and/or the endothelial cell membrane of the affected lung capillaries. Activated neutrophils and platelets were more numerous in the pulmonary capillaries following EVC. These data suggest that the presence of FDP and/or fibrin deposits within the pulmonary microvasculature may influence the early functional integrity of pulmonary endothelial cells at sites of fibrin accumulation.
...
PMID:Pulmonary fibrin deposition and increased microvascular permeability to protein following fibrin microembolism in dogs: a structure-function relationship. 330 21

The solution properties of fibrinogen and the thrombin-induced activation and gelation of fibrinogen in 95% D2O at pH 7.4 were compared to those in H2O under similar conditions. The initial release rates of fibrinopeptides A and B in D2O were slightly slower than those in H2O. However, the values of the Michaelis-Menten parameters Km and V for the release of the two peptides in D2O and H2O in the presence of 0.5 M NaCl were about the same. From turbidity measurements at 450 nm it is obvious that fibrinogen is soluble in a slightly more narrow range of NaCl concentration and that the fibrin gels have a higher degree of lateral aggregation in D2O than in H2O. The variation of fibrinogen concentration, thrombin concentration, pH and ionic a strength have a similar dependence on the final gel structure and clotting time in D2O and H2O. SDS-gel electrophoresis on fibrin samples, which were cross-linked by factor XIII, yielded results where the cross-linking of the gamma-chain appeared to be the same in D2O and H2O. The alpha-chain cross-linking was somewhat faster in D2O than in H2O. When fibrinogen solutions in 95% D2O were incubated at 20 mM CaCl2, a slow gelation of fibrinogen was observed, which was found to be induced by trace amounts of factor XIII. The final gel turbidity appeared to be about the same for this gelation as for that induced by thrombin. The differences in solubility for fibrinogen, kinetics for the enzyme reaction and optical properties for the fibrin gels in D2O and H2O may be explained by differences in electrostatic interactions, hydrogen bonding and hydration of fibrinogen in these two media.
...
PMID:Polymerization and gelation of fibrinogen in D2O. 337 58

Effects of depth of anesthesia, pH of fibrinogen and thrombin, and interventions in the vagus nerves on the development of fibrin-induced pulmonary edema were examined in the rat. Rats were anesthetized with an intraperitoneal injection of pentobarbital sodium, 25 or 50 mg/kg. Solutions of fibrinogen and thrombin at the same pH were separately injected into the cisterna magna. The pH values were adjusted to 6.5 or 8.5 with Tris buffer. Interventions in the vagus nerves, which consisted of atropine administration at a dose of 1 mg/kg, i.v. or bilateral vagotomy, were performed before the intracisternal injection of fibrinogen and thrombin. Animals in which no interventions in the vagus nerve was performed were designated as intact rats. Lung-water ratio was calculated as a ratio of the difference between wet and dry lung weight to dry lung weight. Incidences of pulmonary edema and lung-water ratios were lower under deep anesthesia than under light anesthesia. Both parameters were low in the vagotomized rats treated under deep anesthesia with fibrinogen and thrombin at a pH of 8.5, as compared to those treated similarly at pH 6.5. This phenomenon was not observed under light anesthesia. Interventions in the vagus nerves influenced the development of pulmonary edema to various degrees, depending on the pH values of the injected fibrinogen and thrombin. As suggested from these results, well-defined, specific conditions are required for investigating the mechanism triggering the development of fibrin-induced pulmonary edema.
...
PMID:Factors influencing fibrin-induced pulmonary edema. 337 36

The adverse effects of protamine sulfate, used to neutralize the anticoagulant action of heparin, include systemic hypotension, pulmonary artery hypertension, thrombocytopenia and leukopenia. For further evaluation of protamine's mechanism of action, a three-part investigation was performed. In part I platelet-rich plasma (PRP) was prepared from canine blood samples (n = 6) taken before and 2 minutes after injection of protamine. In part II human PRP (n = 5) was preincubated with protamine or distilled water. Adenosine diphosphate-induced aggregation of protamine-treated platelets was unchanged, but thrombin-induced aggregation was inhibited in both canine and human preparations (p less than 0.05). In part III thrombocytopenia was produced in splenectomized dogs (n = 5), using microporous filters, to 4.5-8.4% of the initial platelet count. Protamine reversal of the heparinization caused hypotension (maximally -29 mmHg 90 s after protamine), but not pulmonary arterial hypertension. Leukopenia developed before additional thrombocytopenia appeared. Protamine-platelet interaction inhibits thrombin-induced platelet aggregation. Platelets may play an important role in the pulmonary pressure rise during protamine reversal, but do not mediate the systemic hypotension.
...
PMID:The effect of protamine sulfate on platelet function. 338 50

Platelet aggregation and fibrin deposition in the pulmonary circulation may contribute to the pathogenesis of lung injury in the adult respiratory distress syndrome (ARDS). We evaluated the effect of two antiplatelet drugs (forskolin & dipyridamole) on pulmonary responses to intravenous infusion of 100 NIH units of thrombin per kg bw in anesthetized, and ventilated rabbits treated with fibrinolysis inhibitor. Thrombin infusion resulted in pulmonary hypertension and increased arterial CO2 tension (PaCO2) and dead space ventilation (VD/VT). Arterial oxygen tension (PaO2) and numbers of circulating leukocytes and platelets dropped after thrombin infusion. These early hemodynamic changes correlated with histological evidence of entrapped leukocytes in the pulmonary microcirculation and transient alveolar edema. Microthrombi were rarely observed in animals that received thrombin. There was little evidence for endothelial damage or progressive lung water accumulation. Treatment with forskolin or dipyridamole reversed thrombin-induced changes in pulmonary artery pressure, PaCO2, VD/VT and systemic oxygenation. Moreover, forskolin and dipyridamole blunted the drop in circulating leukocytes and prevented the development of alveolar edema following thrombin. The beneficial actions of these agents may be due to interference with the release of mediators from leukocytes or platelets.
...
PMID:Effects of antiplatelet drugs on pulmonary responses to thrombin in anesthetized rabbits. 344 3

A new approach has been developed to circumvent the problems of false positive reactions in the Limulus Amoebocyte Lysate (LAL) assay for lipopolysaccharide (LPS) in root surface materials. These LAL-reactive materials include thrombin, thromboplastin, ribonuclease, ribonucleic acid, lipoteichoic acid and peptidoglycan fragments. In the present study, hot phenol/water extraction of these substances followed by ultracentrifugation of the resulting aqueous phases reduced their concentrations to very low levels. Furthermore, the application of Polymyxin B/Sepharose 4B affinity chromatography to these extracts enabled their intrinsic LAL-activity to be determined. Use of these techniques to assay root surface materials has identified LPS as being the major LAL-reactive material present. The mean LPS yield for the periodontally involved teeth was 4.13 micrograms/tooth, representing 2.82 micrograms/root. In contrast, the mean yield of LPS for the periodontally uninvolved teeth was 3.12 ng/tooth.
...
PMID:Identity of limulus amoebocyte lysate-active root surface materials from periodontally involved teeth. 346 18

Fibrin-monomer-Sepharose was used to study thrombin binding to fibrin and the role of the enzyme active centre in this interaction. Binding properties of preformed enzyme-inhibitor complexes, as well as inhibition of thrombin already adsorbed to fibrin monomer, were investigated. No apparent difference was found in binding properties of phenylmethanesulphonyl fluoride-, D-Phe-Pro-Arg-CH2Cl- and dansylarginine NN-(3-ethylpentane-1,5-diyl)amide-inhibited thrombins. Also, the elution profile of phenylmethane-sulphonyl fluoride-inhibited thrombin from fibrinogen-Sepharose was identical with that of active thrombin from fibrin-monomer-Sepharose. Thus far the only low-Mr inhibitor that prevents thrombin from binding to fibrin monomer is pyridoxal 5'-phosphate. Preformed hirudin-thrombin complexes do not interact with fibrin. The extent to which the active centre of thrombin associated with fibrin is still accessible to substrates and inhibitors was also studied. Thrombin bound to fibrin hydrolyses a synthetic substrate at the same rate as the free enzyme. Water-soluble low-Mr inhibitors such as D-Phe-Pro-Arg-CH2Cl and dansylarginine NN-(3-ethylpentane-1,5-diyl)amide can readily modify the active centre of the fibrin-associated enzyme, and the active centre is exposed to the degree that displacement of dansylarginine NN-(3-ethylpentane-1,5-diyl)amide by D-Phe-Pro-Arg-CH2Cl is possible without disturbing the binding. Hirudin disrupts the affinity between thrombin and fibrin. These data indicate that the active centre of thrombin associated with fibrin through extended binding is fully exposed and freely accessible. It is possible that extended binding may play a regulatory role in the activation of Factor XIII by thrombin, as well as inactivation of this enzyme by antithrombin III.
...
PMID:Inhibited thrombins. Interactions with fibrinogen and fibrin. 359 82

Sixty healthy men in three physical fitness categories (sedentary, on no organized fitness program; joggers, running 5-15 miles/wk; and marathoners, running greater than 50 miles/wk) were evaluated for changes in blood clotting and fibrinolytic activity before and after maximum exercise on a treadmill according to the Bruce protocol. The rate of blood clotting, as measured by prothrombin times, partial thromboplastin times and thrombin times, was accelerated by exercise (all P less than 0.005). The ability of euglobulin clots and plasma clots to lyse incorporated 125I-fibrin, termed 125I-euglobulin clot lysis (IEL) and 125I-plasma clot lysis (IPCL), were used as indexes of fibrinolytic activity. Marathoners had greater increases in fibrinolytic activity with exercise (76% compared with 63% for joggers and 55% for sedentary subjects by IEL; 427% compared with 418% for joggers and 309% for sedentary subjects by IPCL; all P less than 0.05). Fibrin degradation products increased with exercise (P less than 0.005 for the total group of 60 subjects). The absolute concentrations of alpha 2-plasmin inhibitor, alpha 2-macroglobulin, and antithrombin III increased with exercise (all P less than 0.005), but when concentrations were corrected for acute shifts of plasma water during exercise, the quantity of these inhibitors actually decreased (all P less than 0.005). The changes in clotting assays with exercise were not significantly correlated with changes in whole blood lactate, blood pyruvate, or rectal temperatures. Fibrinolytic assays before and after exercise correlated poorly to moderately with blood lactates (IEL: r = 0.441 and r = 0.425, respectively; IPCL: r = 0.294 and r = 0.544, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effects of exercise and conditioning on clotting and fibrinolytic activity in men. 359 18

The objectives of this study were to describe the morphological alterations of the pulmonary microvasculature in anesthetized dogs infused intravenously with alpha-thrombin (111-233 NIH U/kg) and to measure the protein reflection coefficient (sigma d), an index of pulmonary vascular permeability to proteins. Quantitative electron microscopy of lung biopsies from a group of four dogs showed an increase in the volume density of the alveolar interstitium and an increase in intravascular fibrin at 30 min after the thrombin infusion. The pulmonary microvascular endothelium was often swollen, blistered, highly vacuolized, or rarefied when close to or in contact with fibrin but appeared normal when not closely associated with fibrin. Fibrin-endothelial interactions often included projections of endothelium surrounding fibrin, the presence of fibrin within endothelial cells, 10- to 15-nm bridges connecting fibrin and endothelium, and disruption of the endothelial plasmalemma in contact with fibrin. Alveolar epithelial cells were unaffected by the thrombin infusion. Pulmonary lymph was collected from an afferent lymphatic to the left tracheobronchial lymph node in a second group of five dogs anesthetized with pentobarbital sodium intravenously. Thrombin increased pulmonary lymph flow by sevenfold and also increased the extravascular lung water-to-bloodless dry lung weight ratio. Left atrial pressure was elevated after thrombin infusion until a filtration-independent state was approached for the calculation of sigma d. Thrombin decreased sigma d from a normal value of 0.62 +/- 0.02 to 0.53 +/- 0.02. Thus thrombin-induced intravascular coagulation in dogs produced focal disruptions of the microvascular endothelium associated with intravascular fibrin and increased the pulmonary vascular permeability to proteins.
...
PMID:Lung morphological and permeability changes induced by intravascular coagulation in dogs. 363 Dec 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---