Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An evaluation of the coagulation system has been conducted in vitamin E and/or selenium deficient swine. The partial thromboplastin time, plasma fibrinogen concentration, platelet lipid peroxides, as well as the fibrinogen/fibrin degradation products were not found to be significantly affected by either vitamin E deficiency, selenium deficiency, or deficiency of both. With selenium deficiency, the prothrombin time was shortened (p less than 0.05). The platelet count and platelet turnover were greatly decreased by both vitamin E (p less than 0.001) and selenium deficiency (p less than 0.005). Further-more, the survival of platelets labelled with 75Se-selenomethionine and the per cent isotope incorporated into platelets were reduced (p less than 0.05 and p less than 0.005) in association with vitamin E deficiency, but not with selenium deficiency. These results were interpreted as evidence of a platelet production defect and possibly a platelet function defect in vitamin E deficient animals. Selenium deficiency were also associated with decreased (p less than 0.05) survival of fibrinogen labelled with 75Se-selenomethionine and increased (p less than 0.05) turnover of fibrinogen. From these fibrinogen kinetic findings, it was considered that chronic low grade disseminated intravascular coagulation possibly occurs in selenium deficient animals, probably in relation to the development of hepatosis dietetica or widespread microvascular damage. However, other possibilities such as increased fibrinogenolysis in relation with hepatosis dietetica or an intrinsic fibrinogen defect due to selenium deficiency also need to be taken into consideration and have not been ruled out in the present study.
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PMID:Studies on vitamin E and selenium deficiency in young pigs. IV. Effect on coagulation system. 83 91

A 13-wk study was conducted by administering d-alpha-tocopheryl acetate (vitamin E) in corn oil by gavage to groups of ten male and ten female Fischer 344 rats at doses of 0, 125, 500 or 2000 mg/kg body weight daily for 13 wk. The dose of corn oil given was 3.5 ml/kg. Additional groups of ten males and ten females were included and served as untreated controls. Deaths occurred only in males at 2000 mg/kg. Vitamin E dosing had no effect on body weight or food consumption. The liver-to-body weight ratio of females at 2000 mg/kg was significantly increased. In males, high levels of vitamin E (2000 mg/kg) caused prolongation of both prothrombin and activated partial thromboplastin (APTT) times, reticulocytosis and a decrease in haematocrit values and haemoglobin concentrations. APTT was also lengthened in females at this dose level. High levels (2000 mg/kg) caused haemorrhagic diathesis in both males and females and increased medullary erythropoiesis in the spleen of one male. Vitamin E at all doses tested caused interstitial inflammation and adenomatous hyperplasia of the lung. The above findings indicate that vitamin E administration in excessive amounts is potentially toxic.
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PMID:Thirteen-week toxicity study of d-alpha-tocopheryl acetate (vitamin E) in Fischer 344 rats. 380 11

During a Phase I study of intravenous vitamin E-free alcohol (all-rac-alpha-tocopherol or Ephynal) in patients with neuroblastoma, we noticed a bleeding diathesis in two patients receiving 2300 mg/m2 daily for four or more days in succession. Both blood prothrombin time and accelerated partial thromboplastin times were prolonged. These spontaneously returned to normal levels three days after interrupting vitamin E infusions. It was also noted that factors VII, IX and X were decreased, which corresponded with the prolonged PT and APTT. It was found that by infusing menadiol sodium diphosphate just prior to the vitamin E, these inhibiting effects on procoagulant factors could be abrogated and high dosages of vitamin E-free alcohol safely given.
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PMID:The effect of intravenous vitamin E and menadiol sodium diphosphate on vitamin K dependent clotting factors. 647 8

The effect of vitamin E on endotoxin-induced experimental disseminated intravascular coagulation (DIC) was studied in rats deficient in and supplemented with vitamin E. Experimental DIC was induced by a 4-hr sustained infusion of endotoxin at a dose of 13.3 mg/kg. After the infusion, fibrinogen and fibrin degradation products were increased, platelet count and fibrinogen level were decreased, and prothrombin time and partial thromboplastin time were prolonged. In addition, the number of renal glomeruli with fibrin thrombi was increased. These changes were significantly greater in vitamin E deficient rats when compared to those changes found in rats supplemented with vitamin E. These results indicate that vitamin E plays a protective role in endotoxin-induced DIC.
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PMID:Endotoxin-induced disseminated intravascular coagulation in vitamin E deficient rats. 674 Jun 68

Experimental disseminated intravascular coagulation (DIC) can be induced by 4 hr sustained infusion of endotoxin in a dose of 100 mg/kg in rats. The experimental model of DIC in rats was used to study the preventive effect of vitamin E, alpha-tocopheryl acetate, against DIC. Before the infusion of endotoxin, 0.01, 0.1, 1.0 or 10.0 mg/kg/day of alpha-tocopheryl acetate was injected intraperitoneally for 4 successive days. The preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the number of renal glomeruli with fibrin thrombi, in rats treated with 1.0 or 10.0 mg/kg of alpha-tocopheryl acetate. From these results, it was shown that vitamin E, alpha-tocopheryl acetate, inhibited endotoxin-induced experimental DIC in rats.
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PMID:Effect of vitamin E on endotoxin-induced disseminated intravascular coagulation in rats. 717 3

The importance of lipoproteins in the etiology of atherosclerosis is well established. Evidence is now accumulating to implicate thrombin in the pathogenesis of atherosclerosis. We have investigated whether atherogenic lipoproteins can support thrombin generation. In the absence of platelets or endothelial cells, both very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (LDL) support assembly of the prothrombinase complex and generation of thrombin. Thrombin generation (per microgram of apolipoprotein) supported by VLDL was 19.4-fold greater than that supported by high-density lipoprotein (HDL), P < .00001, and 11.7-fold greater than that supported by LDL, P < .00001. Oxidation of LDL increased lipoprotein-supported thrombin generation 12-fold compared to unmodified LDL, P < .0001. We have shown that the phenomenon of lipoprotein-supported thrombin generation is mediated predominantly by specific phospholipids and is enhanced by oxidation of these phospholipids. The addition of vitamin E (alpha-tocopherol) markedly reduced the increase in thrombin generation observed after oxidation of LDL (822 +/- 57 v 138 +/- 47 nmol/L; P < .0001). These effects suggest that lipoproteins are important in the production of thrombin and that vitamin E may confer protection from the detrimental effects of lipoprotein oxidation by limiting thrombin formation. These results suggest that atherogenic lipoproteins are linked to the development of atherosclerosis in part by their capacity to support thrombin generation.
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PMID:Atherogenic lipoproteins support assembly of the prothrombinase complex and thrombin generation: modulation by oxidation and vitamin E. 942 4

Many studies suggest that a diet supplemented with fish oil concentrates (FOCs) may provide protection against cardiovascular and other diseases. The possible harmful effects of long-term consumption of high doses of FOCs, however, have not been adequately investigated. Corn oil, fish oil (MaxEPA) and various mixtures of the oils were administered by gavage to 120 male and 120 female rats, 5 d/wk for 13 wk at the rate of 5 mL/kg/d. Although MaxEPA had no effect on prothrombin time or activated partial thromboplastin time, it caused a statistically significant diminution of the total serum cholesterol level. Correlations between relative liver and spleen weights and dose levels were positive but a negative correlation was found between dose levels and serum vitamin E concentration. In female rats, the negative correlations between dose levels and serum iron and triglyceride levels were highly significant. The pathology data showed no remarkable lesions in any of the tissues examined. Results of this study suggest that long-term consumption of high levels of FOCs in rats may reduce serum cholesterol and triglycerides and adversely affect serum iron level and relative liver weight in female rats and relative spleen weights in both sexes.
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PMID:Effects of long-term consumption of high doses of fish oil concentrates on clinical parameters in male and female rats. 1068 8

Vitamin E is one of the most widely used antioxidants in cryopreservation and preservation technology. The objective of this study is to examine the effect of vitamin E on platelets and the coagulation system. Vitamin E was added at different concentrations in the range between 0.25 and 5 mM to donor plasma. Using a STA/STA Compact coagulation analyzer the following clotting tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT). The control clotting times PT (13.80 +/- 0.4 s), APTT (27.4 +/- 2.4 s) and TT (17.6 +/- 0.4 s) remained unchanged in the presence of vitamin E. The effect of vitamin E on platelets was assessed by platelet-induced clot retraction (PICR) and aggregation by thrombin. PICR was unaffected by vitamin E. Platelet aggregation, however, was profoundly inhibited by vitamin E. We found that inhibition of platelet aggregation by vitamin E was concentration dependent: increasing with increasing vitamin E concentration. This inhibitory effect, however, was widely reversible upon dilution of vitamin E with autologous platelet-poor plasma.
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PMID:Effects of alpha-tocopherol on platelets and the coagulation system. 1167 55

The recent discovery that vitamin E (VE) regulates gene activity at the transcriptional level indicates that VE may exert part of its biological effects by mechanisms which may be independent of its well-recognised antioxidant function. The objective of this study was the identification of hepatic vitamin E-sensitive genes and examination of the effects of VE on their corresponding biological endpoints. Two groups of male rats were randomly assigned to either a VE-sufficient diet or to a control diet deficient in VE for 290 days. High-density oligonucleotide microarrays comprising over 7000 genes were used to assess the transcriptional response of the liver. Differential gene expression was monitored over a period of 9 months, at four different time-points, and rats were individually profiled. This experimental strategy identified several VE-sensitive genes, which were chronically altered by dietary VE. VE supplementation down-regulated scavenger receptor CD36, coagulation factor IX and 5-alpha-steroid reductase type 1 mRNA levels while hepatic gamma glutamyl-cysteinyl synthetase was significantly up-regulated. Measurement of the corresponding biological endpoints such as activated partial thromboplastin time, plasma dihydrotestosterone and hepatic glutathione substantiated the gene chip data which indicated that dietary VE plays an important role in a range of metabolic processes within the liver.
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PMID:Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats. 1515 15

A case of excessive postoperative bleeding in a 50-year-old woman undergoing breast surgery is reported. Preoperatively, the patient consumed a daily dose of vitamin E of 500 mg, which is far more than the recommended daily intake of 8-10 mg. There is reason to believe that the extensive postoperative bleeding was due to vitamin E-induced inhibition of protein kinase C, which decreases platelet adhesion. Preoperatively, blood samples showed normal prothrombin time index, activated partial thromboplastin time and platelet count, and no other explanation for the excessive bleeding was found.
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PMID:[Vitamin E and excessive bleeding]. 1633 61


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