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)

The effect of renal cytomedin on coagulative and microcirculatory hemostasis and lipid peroxidation was studied in 30 Wistar rats with induced Heymann's nephritis. The course of nephritis caused activation of lipid peroxidation, development of the syndrome of disseminated intravascular coagulation of blood in the animals, and diminution of antiaggregation properties of the kidney. Administration of the polypeptide normalized these processes. Thus, the discussed cytomedin produces a marked positive regulatory effect in experimental renal pathology.
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PMID:[Effect of renal peptides-cytomedins on blood coagulation and lipid peroxidation in experimental Heymann nephritis]. 180 91

Vitronectin, also known as serum-spreading factor or S-protein, mediates cell adhesion and inhibits formation of the membrane-lytic complex of complement and the rapid inactivation of thrombin by antithrombin III in the presence of heparin. Vitronectin is normally present in plasma at a concentration of approximately 300 micrograms/mL. The investigators quantified plasma vitronectin with an enzyme-linked immunosorbent assay and visualized reduced and nonreduced vitronectin by immunoblotting after separation of plasma or serum by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The concentration of plasma vitronectin was markedly reduced in some patients with disseminated intravascular coagulation, especially in those with liver failure; it was near normal in patients with metastatic cancer and acute leukemia. Patients with vitronectin levels less than 40% normal invariably had low fibrinogen and antithrombin III and a prolonged prothrombin time. In both normal and patient plasmas there was heterogeneity in the ratio of the 75,000- and 65,000-mol wt polypeptides of reduced vitronectin: 18% had mostly the 75,000-mol wt polypeptide, 59% had roughly equal amounts of the two polypeptides, and 22% had mostly the 65,000-mol wt polypeptide. This polymorphism is inherited and appears to be due to two alleles that are present with approximately equal frequency. The blotting patterns of vitronectin in reduced and nonreduced plasmas were largely unaltered in plasma of patients with defibrination syndrome, fibrinolysis, liver failure, sepsis, metastatic cancer, and acute leukemia. There was no evidence of fragmentation of vitronectin or formation of the disulfide-bonded complex of vitronectin and thrombin-antithrombin III that is found when blood is clotted. Thus these results corroborate in vitro observations that the liver is the major source of plasma vitronectin, suggest that vitronectin may become depleted during disseminated intravascular coagulation, and define a genetic polymorphism of vitronectin.
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PMID:Plasma vitronectin polymorphism in normal subjects and patients with disseminated intravascular coagulation. 245 67

Thrombin plays a key role in thrombosis and haemostasis, and is selectively inhibited by hirudin and synthetic inhibitors. Hirudin, a polypeptide (molecular weight 7,000 daltons) extracted from medicinal leeches, can now be produced by gene technology. Hirudin binds selectively to thrombin with high affinity and inhibits its enzymatic properties. Besides heparin, hirudin is not inhibited by platelet factor 4; it prolongs in vitro and ex vivo routine blood coagulation assays and prevents thrombosis in a number of animal models without increasing haemorrhagic risk. In humans, hirudin disappears from the blood with a half-life of 1 h, is devoid of undesirable side effects and has been shown to be efficient in the treatment of chronic disseminated intravascular coagulation (DIC). A number of synthetic direct thrombin inhibitors have been described, including benzamidine derivatives which share identical pharmacological properties with hirudin; however their biological half-life after i.v. injection is shorter. Other derivatives (amidino-phenyl-pyruvic acid) have longer half-lives and have been used to treat chronic DIC in man.
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PMID:Pharmacology of selective thrombin inhibitors. 304 69

Factor VIII antigen (VIII:CAg) exhibits molecular weight heterogeneity in normal plasma. We have compared the relative quantities of VIII:CAg forms present in normal individuals (n = 22) with VIII:CAg forms in renal dysfunction patients (n = 19) and in patients with disseminated intravascular coagulation (DIC; n = 7). In normal plasma, the predominant VIII: CAg form, detectable by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was of molecular weight 2.4 X 10(5), with minor forms ranging from 8 X 10(4) to 2.6 X 10(5) D. A high proportion of VIII:CAg in renal dysfunction patients, in contrast, was of 1 X 10(5) mol wt. The patients' high 1 X 10(5) mol wt VIII: CAg level correlated with increased concentrations of serum creatinine, F1+2 (a polypeptide released upon prothrombin activation), and with von Willebrand factor. Despite the high proportion of the 1 X 10(5) mol wt VIII:CAg form, which suggests VIII:CAg proteolysis, the ratio of Factor VIII coagulant activity to total VIII:CAg concentration was normal in renal dysfunction patients. These results could be simulated in vitro by thrombin treatment of normal plasma, which yielded similar VIII:CAg gel patterns and Factor VIII coagulant activity to antigen ratios. DIC patients with high F1+2 levels but no evidence of renal dysfunction had an VIII:CAg gel pattern distinct from renal dysfunction patients. DIC patients had elevated concentrations of both the 1 X 10(5) and 8 X 10(4) mol wt VIII:CAg forms. We conclude that an increase in a particular VIII:CAg form correlates with the severity of renal dysfunction. The antigen abnormality may be the result of VIII:CAg proteolysis by a thrombinlike enzyme and/or prolonged retention of proteolyzed VIII:CAg fragments.
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PMID:Abnormal factor VIII coagulant antigen in patients with renal dysfunction and in those with disseminated intravascular coagulation. 393 66

With the aid of an asphyxia model in rabbit fetuses the possibility of diaplacental influence on the hypoxic effects of the fetal organism has been investigated. The trial to change the vasotonia during the asphyctic shock by sympathicomimetic or -lytic drugs (Dilatol, Obsidan, Ergocomb, Regitin) remained to be without any effect on the DIC in the fetal organism. Trying to seal the vascular wall by the high-molecular-weight basic polypeptide Aprotinin there seemed rather to be an increase of the intravascular fibrin sedimentation.
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PMID:[Diaplacental influence on the disseminated intravascular coagulation (DIC) in an asphyxia model. I. Influence on the vasal tonus and on the vasal wall (author's transl)]. 616 51

Recently, we have found that defibrination of rats with Malayan pit viper venom induces a 10-38-fold increase in the levels of translatable fibrinogen mRNA in the liver. We have used this response to obtain cDNA clones for the three polypeptide chains of rat fibrinogen. A large cDNA library was created in pBR322 from induced rat liver polyadenylated RNA by the poly(dG, dC)-tailing method. Part of this library was screened using colony hybridization with [32P]cDNA prepared from induced and noninduced rat liver RNA. Colonies consistently giving a more intense signal with the induced [32P]cDNA were considered possible fibrinogen recombinants and were used for hybrid selection and translation of mRNA. In this way, cDNA clones for each of the three fibrinogen mRNA's were identified. Analysis of polyadenylated RNA by Northern blotting indicates that the three chains are synthesized from mRNA's of 2300, 2050, and 1950 nucleotides for the alpha, beta, and gamma chains, respectively. The fact tha each of the three chains has a separate mRNA indicates that the highly coordinated regulation of the three messages for rat fibrinogen does not occur by translation of a common cytoplasmic RNA.
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PMID:Molecular cloning of cDNA for the alpha, beta, and gamma chains of rat fibrinogen. A family of coordinately regulated genes. 616 15

Six patients with disseminated intravascular coagulation (DIC) in association with acute promyelocytic leukemia (APL) were studied with sensitive radioimmunoassays that are able to quantitate the extent of thrombin generation within the human circulation. The levels of prothrombin activation fragment, F1 + 2, and thrombin-antithrombin complex (TAT) were obtained at clinical presentation and were then followed serially in several patients during induction chemotherapy. The antileukemic therapy often resulted in a rise in the plasma levels of these molecular species. Simultaneous measurements of fibrinopeptide A (FPA) were also obtained, and the concentrations of this polypeptide were correlated with the levels of F1 + 2 and TAT in patients who were not receiving heparin. Nine individuals with other morphological subtypes of acute nonlymphocytic leukemia (ANLL) were investigated and were usually found to have increased levels of F1 + 2, TAT, and FPA at clinical presentation. However, the magnitude of the elevations was considerably greater and the correlation between TAT and FPA levels was stronger in APL than in ANLL. These studies provide direct evidence that patients with APL, as well as ANLL, generate excessive amounts of thrombin within their vascular system. Furthermore, the data suggest that the concentrations of F1 + 2, compared with the levels of FPA, may be a more sensitive indicator of hemostatic system hyperactivity in individuals with DIC.
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PMID:Thrombin generation in acute promyelocytic leukemia. 659 7

Cell-free translation and hybridization to cloned cDNA probes were used to study variations in fibrinogen mRNA levels in the livers of rats injected with Malayan pit viper venom and glucocorticoids. Animals defibrinated with Malayan pit viper venom showed a rapid and substantial increase in the relative abundance of hepatic mRNAs for the A alpha, B beta, and gamma chains of fibrinogen. The onset, rate, and maximal extent of message accumulation were virtually identical for each of the three fibrinogen polypeptide chains. This response was detectable 1-2 h after injection of venom and, by 12-16 h, fibrinogen species made up approximately 10% of the polyadenylated RNA compared to less than 1% in noninjected animals. Physiologic levels of glucocorticoids appeared to be necessary for maximal levels of message; adrenalectomized animals had a median 4.8-fold increase in fibrinogen mRNA species after defibrination compared with a 12.5-fold increase in normal animals. Although it is uncertain whether the changes in mRNA levels are a function of increased transcription or message stabilization, the similar kinetics of accumulation suggest that a common mechanism is responsible for coordinating the levels of each fibrinogen mRNA.
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PMID:Coordinate accumulation of the mRNAs for the alpha, beta, and gamma chains of rat fibrinogen following defibrination. 689 26

After being envenomated by the timber rattlesnake, a patient was found to have a platelet count of 5000 per microliter, prothrombin time and activated partial thromboplastin time both greater than 150 sec, plasma fibrinogen 0 mg/dl, and fibrinogen split products 2560 microgram/ml. However, this patient did not appear to have acute disseminated intravascular coagulation since coagulation factors II-XII were normal. We postulated that this venom contained, in addition to a fibrinogen clotting enzyme, a platelet activating protein, Crotalocytin. Crotalocytin was purified from crude timber rattlesnake venom by Sephadex G-100 gel-filtration, low ionic strength precipitation, and DEAE-A50 Sephadex chromatography. By sodium dodecyl sulfate gel electrophoresis and gel-filtration Crotalocytin was a single chain polypeptide, molecular weight 55,000. Thrombocytopenia after timber rattlesnake bite appeared to be due to a protein that directly activated platelets. Timber rattlesnake bite mimicked the clinical presentation of disseminated intravascular coagulation.
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PMID:Crotalocytin: recognition and purification of a timber rattlesnake platelet aggregating protein. 743 9

Polypeptide cytomedine, isolated from renal tissues has been studied for its regulatory effect on hemocoagulation and lipid peroxidation with fluoric intoxication (FI). FI was caused by inoculation of laboratory animals (guinea pigs) with sodium fluoride (100 mg/kg) for 14 days. Following it polypeptide (0.1 mg/kg) was introduced intramuscularly for 7 days. The development of FI was expressed by hypercoagulation delay of fibrinolysis with para-coagulation products appearing in blood decrease of antiaggregation activity of the renal tissue. These phenomena were estimated as manifestations of the first phase of disseminated intravascular blood coagulability (DIC-syndrome). The above reactions proceeded simultaneously with lipid peroxidation activation decrease of the antioxidant protection. The necrotic-dystrophic processes developed in renal and hepatic parenchyma. The renal peptide-cytomedine induced the normalization of lipid peroxidation in blood and renal tissues and fibrinolysis, the decrease in the concentration of para-coagulation products. The pathological changes decreased both in the renal and hepatic tissues. It is possibly, a result of the normalization of secretion and reabsorption in the kidneys. Thus, cytomedine of the kidney exerts a pronounced regulatory and protective effect in the case of acute renal pathology. These results correspond to the conception of the peptidergic organism regulation.
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PMID:[Effect of regulatory renal polypeptides on hemocoagulation and lipid peroxidation in fluoride intoxication]. 840 50


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