Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The components of the factor VIII complex were estimated by immuno- and bioassays in 85 patients with liver disease. The plasma concentrations of the antigens were elevated in 65% (VIII:CAg) and in 76% (VIIIR:Ag) of patients while the biological activities were elevated in only 14% (VIII:C) and 15% (VIII:RiCof). There was no correlation with C-reactive protein, used as a measure of an acute phase reaction (X2 = 0.7; P = 0.1); or with severity of liver disease as judged by prothrombin ratio (P = 1.0) but highest values were observed in patients with cholestatic liver disease. Following parenteral vitamin K there was a significant fall in both the biological activity of VIIIC (36%) and of VIII:CAg (38%) in 13 vitamin K deficient patients (P less than 0.001) but no change in 23 vitamin K replete patients or in the VIIIR:Ag levels in either group. Factor V levels were lower in patients with parenchymal liver disease (0.54 +/- 0.1 units/ml, mean +/- SEM, n = 12; normal range 0.5-1.5 units/ml) than in patients with extrahepatic cholestasis who were vitamin K deficient (1.2 +/- 0.1 units/ml, P less than 0.0001). The levels of protein C antigen, the vitamin K dependent protease which inactivates factors VIII:C and V, was at the lower end of the range in both groups (0.7 +/- 0.1, mean +/- SEM, n = 18, normal range 0.74-1.4 units/ml). There was no significant change in either protein C antigen or factor V following vitamin K. The discrepancy between the biological activity of factor VIII and the antigen levels could represent accumulation of partially degraded factor VIII or production of a hypoactive form. There is no evidence that the reduction in VIIIC and VIII:CAg following vitamin K was mediated by protein C.
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PMID:The effect of liver disease on factors V, VIII and protein C. 393 41

Angiotensin-converting enzyme (ACE) inhibitors have proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. Whether this favorable effect can be related to other models of ischemia and reperfusion has not yet been investigated. Therefore, we studied in a model of syngeneic liver transplantation in the rat the effect of recipient enalapril treatment on postischemic liver injury. Untreated animals served as the control group. Treatment with enalapril was started 5 minutes before reperfusion by intravenous infusion of enalapril at a dosage of 5 mg/kg/h. By means of in vivo microscopy, the sinusoidal perfusion rate and leukocyte adherence in sinusoids and postsinusoidal venules were analyzed during 45 to 60 minutes of reperfusion. Liver function was monitored by measuring bile output over a period of 60 minutes. Analysis of coagulation factors (prothrombin time, factor V, fibrinogen) and liver enzymes (alanine transaminase [ALT], aspartate transaminase [AST]) served for the evaluation of organ dysfunction and damage secondary to ischemia/reperfusion injury. The sinusoidal perfusion rate was significantly improved by enalapril treatment (94.7% [1.0] vs. 75.3% [3.8]; mean [SEM]; P = .005). In addition, leukocyte-sticking in both liver sinusoids and postsinusoidal venules was remarkably reduced in enalapril-treated animals as compared with controls (stickers/lobule: 21.0 [3.3] vs. 59.2 [2.1]; P = .0004; stickers/mm2 venular surface: 20.5 [4.7] vs. 110.3 [18.1]; P = .0004). Moreover, bile output was increased (1.13 [0.35] vs. 0.43 [0.18] g bile/60 min x 100 g liver; P = .06). Values for PT (22.5% [2.1] vs. 9.7% [1.8]; P = .005), factor V 99.4% [9.5] vs. 49.5% [8.5]; P = .007), and fibrinogen (64.1% [7.7] vs. 12.8% [3.2]; P = .001) were significantly improved, paralleled by a remarkable reduction in serum ALT (1,428 U/L [190] vs. 2,315 [248]; P = .02). Our data show for the first time that ACE inhibition in the liver recipient by enalapril attenuates hepatic ischemia/reperfusion damage after experimental liver transplantation. Our results may offer a novel approach to reduce ischemia/reperfusion injury in clinical liver transplantation.
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PMID:Angiotensin-converting enzyme inhibition by enalapril: a novel approach to reduce ischemia/reperfusion damage after experimental liver transplantation. 904 13

Serious thrombotic complications occur in sick neonates, while healthy infants have a very low risk of thrombosis. To better understand the regulation of physiological anticoagulation at birth, components of the protein C pathway were measured in cord plasma samples from 14 full-term healthy newborns and in samples from 10 adult controls. Although zymogen protein C was significantly reduced in cord plasma (mean +/- SEM in cord vs. adult sample 37 +/- 1.4% vs. 90 +/- 5.5%, p < 0.0001), levels of the active enzyme, activated protein C (APC), were not (119 +/- 20% vs. 75 +/- 12%, p = 0.0762). Relative to the protein C level, cord plasmas had a 5.2-fold higher APC level (p < 0.01). The APC increase was partially due to slower inactivation of APC in cord plasma (half-life for APC 50 min in cord plasma vs. 27 minutes in adult plasma). Increased sensitivity of factor V to inactivation by APC in cord plasma was observed since the activated partial thromboplastin time-based APC sensitivity ratio was significantly increased for cord vs. adult plasma samples (2.28 +/- 0.09 versus 1.97 +/- 0.03, p < 0.01). Thus, despite low zymogen protein C, the protein C pathway in newborns seems to be functionally well developed and at an activated stage at birth.
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PMID:Upregulation of the antithrombotic protein C pathway at birth. 984 42

Kininogens have recently been shown to possess antiadhesive, anticoagulant, and profibrinolytic properties and can inhibit platelet activation at low thrombin concentrations. To test whether kininogens have antithrombotic properties in vivo, we devised a model of limited arterial injury confined to removal of the endothelium. Brown-Norway Katholiek strain rats with an absence of low- and high-molecular-weight kininogen due to a single point mutation, A163T, were compared in the thrombosis model to the wild-type animals, which were otherwise genetically identical. Despite an equivalent vascular injury, the mean time (+/-SEM) for a 90% decrease in flow measured by laser Doppler was 38.4+/-17 minutes in the kininogen-deficient rats compared with 194+/-29 minutes in the wild-type animals (P<0.002). The degree of vascular injury was the same. No evidence for disseminated intravascular coagulation (decrease in factor V, antithrombin, or fibrinogen) or excessive fibrinolysis (elevation of fibrinogen degradation products) was found in either group of animals. The results suggest that kininogens have antithrombotic properties at low concentrations of thrombin and that inhibitory peptides derived from kininogen may constitute a new antithrombotic strategy.
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PMID:Kininogens are antithrombotic proteins In vivo. 1047 69

Thrombin regulation in newborns remains incompletely understood. We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor V(Leiden) (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enrolled in the study. Cord blood and venous blood at the age of 14 days were collected from 11 FVL heterozygous newborns (FVL-positive) and from 16 FVL-negative newborns. Prothrombin fragment F1 +2 and coagulation factors were measured. Tissue factor-initiated thrombin formation was studied in cord platelet-poor plasma (PPP) of FVL-negative and -positive newborns, and in both PPP and platelet-rich plasma (PRP) of healthy controls. The endogenous thrombin potential (ETP) in cord PPP or PRP was approximately 60% of that in adult plasma, while thrombin formation started approximately 55% and approximately 40% earlier in cord PPP and PRP, respectively. Further, in FVL-positive newborns thrombin formation started significantly earlier than in FVL-negative newborns. Exogenous activated protein C (APC) decreased ETP significantly more in cord than in adult PRP. In FVL-negative cord plasma 5 nM APC decreased ETP by 17.4+/-3.5% (mean+/-SEM) compared with only 3.5+/-3.8% in FVL-positive cord plasma (p=0.01). FVL-positive newborns showed similar levels of F1 +2 but significantly decreased levels of factorV compared with FVL-negative newborns both in cord plasma (FV 0.82+/-0.07 U/ml vs. 0.98+/- 0.05 U/ml, p=0.03) and at the age of two weeks (FV 1.15+/-0.04 U/ml vs. 1.32+/- 0.05 U/ml, p=0.03). In conclusion, newborn plasma showed more rapid thrombin formation and enhanced sensitivity to APC compared with adult plasma. FVL conveyed APC resistance and a procoagulant effect in newborn plasma. Lack of elevated F1+2 levels in FVL-positive infants, however, suggested the existence of balancing mechanisms; one could be the observed lower level of factor V in FVL heterozygous newborns.
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PMID:The procoagulant effects of factor V Leiden may be balanced against decreased levels of factor V and do not reflect in vivo thrombin formation in newborns. 1652 70