Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methods for the measurement of thrombin and plasma antithrombin, by end point determination at a semi micro level and also by rate assay measurement in a fully automated system have been devised using the thrombin specific chromogenic substrate, H-D-Phe-Pip-Arg-p-nitroanilide. Preliminary defibrination of plasma is avoided in both methods. The semi micro method has been correlated with antitrhombin measured in plasma of postoperative patients by established clotting and immunological assays. The automated method has been found to be highly reproducible and to have less scatter than the other procedures.
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PMID:Methods for semi micro or automated determination of thrombin, antithrombin, and heparin cofactor using he substrate, H-D-Phe-Pip-Arg-p-nitroanilide-2HCl. 7 Feb 86

Using the chromogenic substrate, Tos-Gly-Pro-Arg-pNA-HCl (Chromozym TH, Boehringer Mannheim) plasma thrombin was estimated in six cases of envenomation by Australian elapid snakes. All patients manifested findings characteristic of defibrination due to envenomation by these snakes. Fibrin-fibrinogen degradation products were grossly elevated, as was plasma thrombin in all cases. Following treatment with antivenene, all abnormal coagulation parameters returned rapidly towards normal by 24 hours and plasma thrombin disappeared.
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PMID:Plasma thrombin assay using a chromogenic substrate in disseminated intravascular coagulation due to snake bite envenomation. 46 21

Fibrinogen-fibrin-related antigen (FR antigen) was isolated from as little as 1 ml of human plasma by immuno-affinity chromatography with agarose-bound antibody to human fibrinogen. N-terminal analysis was performed to determine the nature and extent of proteolytic degradation of the FR antigen in patients with disseminated intravascular coagulation and in normal subjects. Thrombin cleavage of the A- and B-peptides from fibrinogen in vitro was monitored by the appearance of N-terminal glycine, and an increase in glycine was shown in the FR antigen of patients with disseminated intravascular coagulation. As plasmin progressively degraded fibrinogen, increases in N-terminal alanine, aspartic acid and lysine were observed, corresponding to the known plasmin-cleavage points of fibrinogen; increases in these N-terminal amino acids were also found in the patients' FR antigen. Thrombin treatment in vitro was used to remove fibrinopeptide A (N-terminal alanine) from the samples and to reflect specifically the N-terminal alanine at the plasmin-cleavage point (Arg-42-Ala-43) of the B beta-chain on assay; this alanine was increased progressively in the FR antigen of a patient during urokinase therapy, and was high in other patients when the FR antigen was examined by this procedure.
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PMID:Quantitative N-terminal analysis of fibrinogen-fibrin-related antigen [FR antigen] from human plasma. 54 36

Both congenital and acquired antithrombin-III (AT-III) deficiencies are amenable to replacement therapy. We describe two antithrombins produced by recombinant DNA techniques from human alpha 1-antitrypsin (alpha 1AT) cDNA in yeast. Alteration of the alpha 1AT active site, replacing methionine 358 with arginine, results in a thrombin inhibition rate similar to that of heparin-activated AT-III. Alteration of two further residues, to give a five-residue sequence identical to AT-III, does not increase this rate further. Neither antithrombin is activated by heparin; both are unglycosylated and have shorter in vivo half-lives (t1/2) than human alpha 1AT. These antithrombins should be suitable for therapeutic replacement of AT-III in cases of congenital deficiency and in conditions associated with acquired AT-III deficiency, such as disseminated intravascular coagulation.
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PMID:Characterization of antithrombins produced by active site mutagenesis of human alpha 1-antitrypsin expressed in yeast. 264 77

It has been shown that epitopes reactive with one group of rabbit antibodies to human fibrinopeptide A (hFPA, A alpha 1-16) are included in its COOH-terminal region (A alpha 7-16). It was further established that Asp-7, Phe-8, and Arg-16 contribute to immunoreactivity and that intact fibrinogen and hFPA-containing fragments react poorly with such antibodies. The purpose of this investigation was to prepare a synthetic peptide corresponding to A alpha 7-16 and use it for generation of FPA-specific monoclonal antibodies (MoAbs). Such probes would allow for development of assays that could measure hFPA directly in plasma. In our approach, an ovalbumin-conjugate of the hFPA homologue served as immunogen. Mouse spleen cells were fused with the immunoglobulin nonsecretor myeloma (P3X63Ag8.653). A hybridoma (8C2-5) has been isolated that secretes an antibody (MoAb/8C2-5) with the following characteristics: (a) IgG1, kappa isotype; (b) equilibrium dissociation constant of 1.5 +/- 0.2 x 10(7) L/mol with the [125I]-labeled N-tyrosyl derivative of hFPA [( 125I] Tyr-hFPA) as ligand; (c) reacts with hFPA and dog FPA (dFPA) but not with the des Arg (A alpha 1-15) or shorter peptides; (d) does not react with intact fibrinogen or A alpha-chain of human or dog origin; (e) does not react with the elastase-generated hFPA-containing peptide A alpha 1-21. Enzyme-based immunoassays (EIAs) have been developed for measuring plasma hFPA levels in the range 3 x 10(-8) to 5 x 10(-7) mol/L. Since it has already been shown by a number of investigators that hFPA levels in patients with overt defibrination fall into this range, we propose that the MoAb/8C2-5-based assays may serve as useful clinical tools in screening patients at risk of thrombosis. The 8C2-5 antibody may also be helpful in studies dealing with congenital dysfibrinogenemias, particularly in identifying heterozygous propositi with amino acid substitutions at any position within the A alpha 7-16 region. Finally, due to its cross-reactivity with dFPA, assays using this antibody should also be valuable in the canine experimental thrombosis model studies.
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PMID:Use of a synthetic homologue of human fibrinopeptide A for production of a monoclonal antibody specific for the free peptide. 275 51

Disseminated intravascular coagulation (DIC) was produced by an infusion of a prothrombin activator (Echis carinatus venom; 30 minutes; 0.5 NIH thrombin equivalent U/kg) in mongrel dogs (Echis group, n = 7). Fibrinogen declined to below measurable levels (less than 25 mg/dl), and fibrin-fibrinogen degradation products appeared (53 +/- 8 micrograms/ml) at end venom infusion in the Echis group. These alterations were not seen when an irreversible thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine-L-chloromethyl ketone (PPACK) (57 nmol/kg/min for 120 minutes), was given alone (PPACK group, n = 5) or in association with venom (Echis + PPACK group, n = 5). Factor II activity (1% +/- 1%) in the Echis and Echis + PPACK groups was significantly below the PPACK (55% +/- 9%) and the control (79% +/- 2%) levels at 120 minutes. In contrast, factor VIII coagulant (factor VIII:C) activity in the Echis group (1% +/- 1%) remained significantly below that in the Echis + PPACK (68% +/- 8%), PPACK (78% +/- 10%), and control (91% +/- 9%) groups at this interval. No change in factors X (91% +/- 7% to 81% +/- 7%, P not significant) and VII (64% +/- 10% to 48% +/- 11%, P not significant) activities were observed. Hemolysis was observed only in the Echis group, whereas thrombocytopenia and leukopenia were noted in both the Echis and the Echis + PPACK groups. These data show that large amounts of E. carinatus venom produce rapid DIC in vivo, because of the activation of prothrombin. In contrast, the decline in factor VIII:C activity appeared to be the result of the liberated thrombin. PPACK antagonized all of the venom-released thrombin without any major deleterious clotting abnormalities. This inhibitor appears to prevent thrombin-mediated DIC in vivo. In contrast, heparin was found to be an unreliable antagonist of the venom-released thrombin in vitro. PPACK also inhibited the marked hemolysis usually observed after venom. In addition, we found that the esterolytic (N-benzoyl-L-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide HCL) activity of E. carinatus venom degrades fibrinogen in vitro.
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PMID:Disseminated intravascular coagulation following Echis carinatus venom in dogs: effects of a synthetic thrombin inhibitor. 308 70

The inhibitory effect of gabexate mesylate, which is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation, and as a regional anticoagulant agent for hemodialysis, has been measured on bovine factor Xa, bovine alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, human urokinase, porcine pancreatic beta-kallikrein-B, and bovine beta-trypsin catalyzed hydrolysis of p-nitrophenyl esters of N-alpha-carbobenzoxy-L-arginine and N-alpha-carbobenzoxy-L-lysine. On the basis of enzyme:gabexate mesylate affinities, the serine proteases can be arranged as follows: human urinary kallikrein approximately porcine pancreatic beta-kallikrein-B much less than bovine beta-trypsin approximately bovine factor Xa approximately human Lys77-plasmin approximately human urokinase approximately bovine alpha-thrombin. The mode of binding of gabexate mesylate to the serine proteases conforms to the active-reactive site geometries observed in their complexes with natural and synthetic inhibitors. Differences in gabexate mesylate affinities for these proteases reflect structural differences at their primary specificity subsite, which have been investigated by comparative analysis of amino acid sequences and by computer-graphics techniques.
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PMID:Gabexate mesylate inhibition of serine proteases: thermodynamic and computer-graphics analysis. 310 78

The toxicity of hemoglobin solutions was studied in the context of their ability to activate serum complement (C). Three bovine polymerized hemoglobin solutions (BPHSs) with different degrees of purity were used for experiments in vitro and in vivo. BPHS-1 contained bacterial endotoxins (E) (5 EU/ml) and stromal phospholipids (PLs) (1.2 mg/dl), BPHS-2 contained only PLs (2.0 mg/dl), while BPHS-3 was completely free of both contaminants. C-activation was studied by the direct measurement of C3a, C4a, and C5a des Arg fragments, using commercially available RIA kits. During 1 hour of incubation with fresh monkey plasma, BPHS-1 and -2 activated both pathways of C, while BPHS-3 caused no activation of any factor. In vivo, Hb solutions were used to replace one-third of blood volume in three groups of six Coebus monkeys each, while fresh homologous plasma was used in a control group of four animals. Impure solutions activated the alternative pathway of C and caused significant reactions of the circulating blood (thrombocytopenia, leukopenia, and disseminated intravascular coagulation) associated with multiorgan dysfunction (cardiac arrhythmias, hypoxemia, reduction of renal clearance of endogenous creatinine, and elevation of liver enzyme SGPT). The pure solution neither activated C nor caused any reaction in the circulating blood. However, it caused a moderate degree of direct tissue injury, evidenced by transient reduction of creatinine clearance and elevation of SGPT. These observations suggest that impure and pure Hb solutions carry separate mechanisms of toxicity. Complement, activated by toxic impurities, plays an active role in the toxicity of impure solutions. C-activation in vitro could be used as a screening test of biocompatibility.
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PMID:Complement activation and the toxicity of stroma-free hemoglobin solutions in primates. 316 73

In vitro effects of S-2441, H-D-Pro-Phe-Arg-NH-Heptyl, include potent anti-bradykinin activity and broad-spectrum inhibition of serine proteases involved in the coagulation cascade. In this study, rats infused with 7.8 X 10(8) viable Escherichia coli were treated either with saline (group A) or with intravenous (0.1 mg) and intraperitoneal (0.4 mg) doses of S-2441 (group B). Survival rates for groups A and B were 68% and 98%, at 12 hours (P less than 0.001), and 37% and 73% at 24 hours (P less than 0.001), respectively. Hematologic studies revealed that S-2441 significantly inhibited E. coli-induced prolongation of prothrombin time and partial thromboplastin time as well as a rapid decrease in the values of factor X, anti-thrombin III, and fibrinogen. In addition, S-2441 attenuated E. coli-induced hypoglycemia and a marked reduction of serum complement level. Ultrastructural evaluation of the liver demonstrated that S-2441 prevented the development of extensive sinusosoidal microthrombosis and hepatocellular necrosis. The results indicate that S-2441 affords protection in lethal gram-negative bacteremia owing in part to attenuation of disseminated intravascular coagulation and complement-mediated reactions. The findings are consistent with the concept that S-2441 and related oligopeptides modulate serine protease-mediated responses involving inhibition of active enzymes with competitive antagonism of pharmcologically active products formed during the activation of coagulation, fibrinolytic, kallikrein, and complement systems.
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PMID:Efficacy of S-2441, a synthetic oligopeptide, in a rat model for gram-negative bacteremia. 388 74

An assay measuring the thrombin inactivating effect of human plasma in the presence of dermatan sulfate (DS) is described. Test plasma, diluted 1/50, is incubated with human thrombin in the presence of DS. Remaining thrombin is determined with chromogenic substrate 2AcOH . H-D-CHG-Ala-Arg-pNA. Three dilutions of reference plasma suffice and the standard curve is linear. Antithrombin III (AT) exerts a small (3-8%) effect in the assay. When test plasma contains heparin above 0.05 U/ml, this unspecific effect of AT increases, but it may be abolished by antibodies against AT. In a normal material (n = 50), the SD of DS cofactor activity was greater (15%) than that of AT (8.7%). DS cofactor was normal in hereditary AT deficiency and in 15 patients with deep venous thrombosis. In liver cirrhosis and in DIC, both inhibitors were markedly depressed, to similar degrees (r = 0.84).
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PMID:Assay of dermatan sulfate cofactor (heparin cofactor II) activity in human plasma. 654 86


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