Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium dehydroacetate (DHA-S) is used as a food additive, preservative and antimicrobial agent. Repeated oral administration of DHA-S in rats induced severe hemorrhage in multiple organs and prolongation of blood coagulation factors. To determine the mechanism of hemorrhage, the protective effect of vitamin K (VK) was investigated. Increased VK-dependent blood coagulation parameters, a prolonged prothrombin time (PT) and an activated partial thromboplastin time (APTT) were observed in rats when DHA-S alone was administered, while only a slight change was observed in animals that received a single injection of vitamin K2 following the DHA-S dosing. These results suggest that DHA-S-induced hemorrhage is caused by a deficiency of vitamin K. In addition, the inhibitory effect of DHA-S on vitamin K1 epoxide reductase (VKOR) activity was measured with an in vitro system using liver microsomes of normal male rats. DHA-S concentration-dependently inhibited VKOR activity similar to warfarin, but the inhibitory concentration was high. Therefore, it was concluded that the DHA-S-induced hemorrhage was caused by a depletion of blood VK, associated with any factors including VKOR inhibition.
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PMID:Anticoagulant effect of sodium dehydroacetate (DHA-S) in rats. 1794 Oct 40

The aim of this study was to evaluate an association of carrier status of common inherited thrombophilic genetic mutations and implantation failure after assisted reproduction (ART): IVF and ICSI. Sixty seven women with failure of embryo implantation and ninety six controls--women without obstetric complication were investigated for carriage of factor V Leiden (FVL), G20210A prothrombin gene mutation, genetic variant C677T in methylentetrahydrofolate reductase gene (MTHFR) and polymorphism A2 in platelet glycoprotein IIb/IIIa (GIPr IIb/IIIa). A significantly higher prevalence of polymorphism A2 in GIPr IIb/IIIa was found in women with implantation failure in ART compared to controls (respectively 26.1% and 12.5%; OR: 2.571, 95% CI: 1.066-6.258, p = 0.033). A higher but not significant prevalence of G20210A prothrombin gene mutation carriage was found inpatients compared to controls (respectively 5.8% and 3.13%, OR: 1.968, 95% CI 0.356-11.539). The carriage of FVL was a little but not significantly higher in controls. The carriage of genetic variant C677T in MTHFR was the same in both groups. These data suggest that polymorphism A2 in GIPr IIb/IIIa and G20210A prothrombin gene mutation could be play a role in the etiology of IVF failures and the carriers of GIPr IIb/IIIa A1/A2 and G20210A prothrombin gene mutation are at higher risk of implantation failure and not successful ART outcome. The carriage of these two genetic defects should be investigated in women undergoing IVF and the antithrombotic or anticoagulant prophylaxis should be indicated for carriers of these two factors.
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PMID:[Risk of thrombophilia in carriers of thrombophilic genetic factors in unsuccessful assisted reproduction]. 1797 63

Small gestational age (SGA) is one of the major causes of fetal mortality and morbidity. Altered maternal homeostasis as a result of point mutations in the coagulation cascade has been reported as an important risk factor for this adverse pregnancy outcome. This study aims to investigate the relationship between mother's thrombophilic mutations and SGA deliveries in our population. The study group was consisted of sixty-six women who gave birth to one or more SGA babies. 104 women who gave birth to appropriate-for-gestational age (AGA) babies were sampled for the control group. Restriction fragment size analysis were performed by visualizing digested PCR products for Factor V Leiden (G1691A), Factor V Cambridge (A1090G), Factor V A1299G, prothrombin G20210A, methylene tetrahydropholate reductase C677T, A1298C and T1317C mutations. The results of this study indicate that maternal C677T (p=0.01) and A1298C (p<0.01) mutations in MTHFR gene may be suggested as risk factors for SGA outcome in our population. Therefore, maternal screening of these two mutations in the first trimester of pregnancy could help in the assessment of patients.
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PMID:Relationship between small-for-gestational age births and maternal thrombophilic mutations. 1804 87

The importance of genetic thrombophilic factors in the development of venous thromboembolism has been increasingly recognized. Factor V Leiden (FVL), prothrombin gene mutation G20210A (FII G20210), genetic variant C677T of the methylentetrahydrofolate reductase (MTHFR), as well as the polymorphism A2 (PlA2) in platelet glycoprotein IIb/IIIa were recently discussed. We analyzed the contribution of genetic thrombophilic factors to the pathogenesis of pulmonary embolism (PE) and their association with the early onset and recurrence of PE using DNA analysis methods. In this case control trial we found thrombophilic genetic variants in 58.8% of 51 patients with PE. FVL was found in 23.5% of the patients versus 7.1% of the 98 controls (p=0.01), PlA2 IIb/IIIa was found in 35.3% vs. 14.3% (p=0.03), and FII G20210A was found in 5.9% vs. 2.0% (NS). Patients with recurrent PE had a very high prevalence of genetic factors, 70.4%. High prevalence of FVL was found in patients under 45 years of age: 39.3% (OR=14.23, 95% CI=1.58-330.03, p=0.01) as well as in patients with recurrent incidence (37%, OR=7.647, 95% CI=2.27-26.44, p=0.001). FVL was also significantly higher in the subgroup of patients with PE combined with deep venous thrombosis (OR=6.500, 95% CI=1.81-23.76, p=0.002) in comparison with patients with isolated PE (OR=2.261, 95% CI=0.50-9.69). The carriers of FVL are at higher risk for early and recurrent PE events. High prevalence of PlA2 in PE patients evidently shows the impact of this polymorphism in PE development. A different treatment should be considered in carriers of thrombophilic defects.
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PMID:Impact of thrombophilic genetic factors on pulmonary embolism: early onset and recurrent incidences. 1809 19

Impaired cochlear blood circulation has been suggested to cause sudden hearing loss. In this study, the role of factor V 1691 G-A (FV 1691 G-A), prothrombin 20210 G-A (PT 20210 G-A), methylene tetrahydrofolate reductase 677 C-T (MTHFR 677 C-T), factor V 4070 A-G (FV 4070 A-G), endothelial cell protein C receptor (EPCR) gene 23-bp insertion, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G mutation was assessed. Fifty-three patients with idiopathic sudden sensorineural hearing loss and 80 individuals comprising the control group were included in this study. The frequency for FV 1691 A was 6.2% in the patient group and 3.7% in the control group, PT 20210 G-A was 1.2% in the patient group and 1.9% in the control group, and FV 4070 A-G was 7.5% in the patient group and 11.3% in the control group. The frequency of MTHFR 677 C-T was significantly higher in the patient group than in the control group, with a P value of .03. PAI-1-675 4G/5G polymorphism was found to be 71.2% and 69.8%, in the control group and the patient group, respectively. The EPCR 23-bp insertion was 0% in the control group and was found in 3 patients (3.7%), which needs further study.
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PMID:The importance of thrombotic risk factors in the development of idiopathic sudden hearing loss. 1816 Jun 2

Pulmonary thromboembolism is a life-threatening condition resulting mostly from lower extremity deep-vein or pelvic-vein thrombosis. A 46-year-old woman was admitted to hospital with pain on the right side of the chest and hemoptysis. On laboratory analysis, D-dimer level was elevated. Computed tomographic pulmonary angiography revealed intravascular filling defects due to thrombi in right lower lobe pulmonary segmental arteries. Screening for thrombophilic states was normal except for heterozygous mutations of both prothrombin and methylene tetrahydrofolate reductase (MTHFR 677) genes. Homocysteine level was high, and vitamin B12 level and serum ferritin level were reduced. Serum antiparietal antibody was positive, and therefore, pernicious anemia was diagnosed along with iron-deficiency anemia. After the diagnoses were established, enoxaparin followed by warfarin was started in addition to oral vitamin B12, pyridoxine, thiamine, folic acid, and ferroglycine sulfate supplementation. At the end of 8 weeks of the replacement therapy, vitamin B12, folate, and homocysteine levels and red cell volume were found to be normal, with complete resolution of the thrombus confirmed by repeat computed tomographic pulmonary angiography. We conclude that hyperhomocysteinemia due to vitamin B12 deficiency associated with pernicious anemia might have decreased the threshold for thrombosis. In addition, the presence of heterozygous prothrombin and methylene tetrahydrofolate reductase mutations might serve as synergistic cofactors triggering pulmonary thromboembolism.
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PMID:Hyperhomocysteinemia due to pernicious anemia leading to pulmonary thromboembolism in a heterozygous mutation carrier. 1858 84

Warfarin is commonly used worldwide as a rodenticide. It inhibits coagulation of blood by inhibiting vitamin K 2,3-epoxide reductase (VKOR) activity. An inadequate supply of vitamin K blocks the production of prothrombin and causes hemorrhage. It has been reported that repeated or long-term treatments with this drug cause resistance in wild rodents. However, the mechanism of warfarin resistance in rodents is still not known precisely. Recent studies reported and identified the function of the molecule, vitamin K epoxide reductase complex subunit 1 (VKORC1), which is the main unit of VKOR. An amino acid substitution in VKORC1 is one of the supposed mechanisms of warfarin resistance. An accelerated detoxification system involving cytochrome P450 (CYP) could also cause the rodenticide resistance. Administration of SKF-525A, a potent inhibitor for P450, increased the mortality due to reduction of warfarin metabolism in warfarin-resistant rats. Meanwhile, the appearance of warfarin-resistant rodents has led to the development of the more effective and toxic rodenticide superwarfarin, which is widely used in Europe and the USA. However, animals resistant to this second-generation rodenticide have already been reported in Europe. In this review, we focus on the mechanism and the pleiotropic effects of pesticide resistance in wild rodents.
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PMID:Pesticide resistance in wild mammals--mechanisms of anticoagulant resistance in wild rodents. 1867 Jan 59

Single nucleotide polymorphisms of the genes coding for coagulation factors are the cause of congenital thrombophilia which might lead to recurrent miscarriages and fetal loss in advanced pregnancy. The most frequent reasons of thrombophilia are the following: factor V Leiden (1691G>A), mutation 20210G>A of prothrombin gene, and 677C>T of 5, 10-methylenetetrahydrofoliate reductase gene. The following article briefly summarizes the administration of antithrombotic prophylaxis (low-molecular weight heparin, acetylsalicylic acid) which seems to be an effective course of action to prevent complications in next pregnancies. What is more, adverse events after long-term usage of low-molecular weight heparin and acetylsalicylic acid in prophylactic doses have not been observed. Due to lack of complete randomized investigation about the inclusion of antithrombotic prophylaxis in this group of pregnant women, common scheme of administration and optimal dosage is yet to be established.
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PMID:[Inherited thrombophilia in women with recurrent miscarriages and pregnancy loss in anamnesis--own experience]. 1893 15

Fenofibrate, a lipid-lowering drug, inhibits hydroxyl-methylglutaryl coenzyme A (HMG-CoA)-reductase activity, thus reducing cholesterol synthesis and increasing the clearance of circulating LDL-cholesterol via the high affinity receptor system. In addition, fenofibrate has beneficial effects such as the inhibition of tissue factor expression, antithrombotic effect and anti-inflammatory effect. The aim of this study was to investigate the effects of fenofibrate on thrombus formation in vivo and platelet activation in vitro and ex vivo. The carotid arteries of male Sprague-Dawley rats were subjected to chemical injury by FeCl(3), and then blood flow was measured with a blood flowmeter. Fenofibrate (200 and 400mg/kg/day for 1 week) delayed the time to occlusion by 61.3% (p<0.05, n=10) and 90.7% (p<0.01, n=10), respectively. Fenofibrate also significantly inhibited ex vivo platelet aggregations induced by collagen (7.5microg/ml) (p<0.01, n=11) and ADP (10microM) (p<0.01, n=11), respectively, but did not affect coagulation times following activated partial thromboplastin and prothrombin activation, indicating the antithrombotic effect was mediated by its inhibition on platelet activation rather than coagulation system. This antiplatelet activity was revealed to be mediated by the suppression of thromboxane A(2) receptor, cytosolic calcium mobilization, and cyclooxygenase (COX)-1 activity. Taken together, we demonstrate that fenofibrate can significantly inhibit artery thrombus formation in vivo, which may be due to antiplatelet activity via the inhibition of thromboxane A(2) receptor, cytosolic calcium mobilization and COX-1 activity, and the beneficial effect of fenofibrate on cardiovascular system may be also due to its modulation of platelet activation.
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PMID:Antithrombotic and antiplatelet activities of fenofibrate, a lipid-lowering drug. 1934 49

There are controversial results related to the contribution of factor V Leiden G1691A, prothrombin gene G20210A and methylentetrahydrofolate reductase (MTHFR) C677T mutations in the development of coronary artery disease (CAD) and their association with diabetes. To assess the distribution of these thrombophilic mutations in CAD patients with and without type 2 diabetes mellitus (T2DM), we studied 117 CAD patients [65 CAD patients with diabetes (CAD/T2DM) and 52 CAD patients without diabetes (CAD/ND)] and 59 age-matched and sex-matched healthy individuals without CAD from population of western Iran. Genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism using Mnl I, Hind III and Hinf I for factor V Leiden, prothrombin G20210A and MTHFR C677T, respectively. The prevalence of prothrombin G20210A variant in CAD/T2DM, CAD/ND and control individuals was 3.1, 1.9 and 0%, respectively. Factor V Leiden G1691A was found in 4.6% of patients with CAD/T2DM, 3.8% of patients with CAD/ND and 3.4% of healthy individuals. The prevalence of MTHFR C677T was found to be 49.2, 32.7 and 44.1% in CAD/T2DM, CAD/ND and control group, respectively. Our results indicate that there is no significant difference between the prevalence of thrombophilic mutations of factor V Leiden, prothrombin G20210A variant and MTHFR C677T in CAD patients with or without diabetes compared with controls. Although a higher prevalence of these thrombophilic mutations was observed in CAD patients, especially in those patients with diabetes, it seems that these variants may not be considered as independent risk factors for CAD or diabetes in our sample. These findings are discussed in relation to available literature.
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PMID:Factor V G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase polymorphism C677T are not associated with coronary artery disease and type 2 diabetes mellitus in western Iran. 1934 59


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