• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1212-1220
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• 2013

The human coagulation factor XI (FXI) is a serine protease that plays a significant role in blocking of the blood coagulation cascade as an attractive antithrombotic target. Selective inhibition of FXIa (an activated form of factor XI) disrupts the intrinsic coagulation pathway without affecting the extrinsic pathway or other coagulation factors such as FXa, FIIa, FVIIa. Furthermore, targeting the FXIa might significantly reduce the bleeding side effects and improve the safety index. This paper reports on a docking-based three dimensional quantitative structure activity relationship (3D-QSAR) study of the potent FXIa inhibitors, the chloro-phenyl tetrazole scaffold series, using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods. Due to the characterization of FXIa binding site, we classified the alignment of the known FXIa inhibitors into two groups according to the docked pose: S1-S2-S4 and S1-S1'-S2'. Consequently, highly predictive 3D-QSAR models of our result will provide insight for designing new potent FXIa inhibitors.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.237-242
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• 2015

The coagulation factor activity compared two groups of the lower 10% (29.1~30.9 sec) and the upper 10% (38.0~41.9 sec) of the normal reference range of aPTT. The aim of this study was to investigate the influence of sex, age, and ABO blood type on coagulation factor activity. There was significant difference in the activity of the coagulation factor assay based on age. The VIII (p<0.0001) and IX (p=0.0050) in the lower group of samples from those over sixty years of age is higher than from those under sixty. In contrast, XII (p=0.0285) for samples over sixty was lower than for samples under sixty. While in the upper group V (p=0.0219), VIII (p=0.0005), and IX (p=0.0014) for samples from the over sixty group was higher than those under sixty. In the case of activity of coagulation factor between O and non-O blood type, VIII (p<0.001) activity of the non-O blood type was higher than that of the O blood type in the both groups. The XII (p=0.016) activity of non-O blood type was lower than that of O blood type in the upper group. According to the multiple logistic regression analysis, when other variables are under the same conditions between lower and upper groups, there is a strong possibility for the lower group when activity of V (p=0.001), VIII (p<0.001), X (p<0.001) and XII (p<0.001) is increased. Furthermore, there is also a strong possibility of upper group when activity of II (p=0.004) and IX (p=0.012) is increased. However, no significant difference in between sex, age and XI was observed.

• Korean Journal of Food Science and Technology
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• v.29 no.4
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• pp.817-822
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• 1997

Inhibitory mechanism of the anticoagulant polysaccharide purified from the fruit body of Coriolus versicolor was investigated in this paper. The anticoagulant polysaccharide (CV-40-Va-1) was proposed to have functions of the inhibition of intrinsic pathway in the blood coagulation pathway together with the interuption of a human platelet aggregation induced by von Willebrand factor (vWF). CV-40-Va-I inhibited other factors of the coagulation cascade such as factor VIII, IX, and as well as thrombin. Especially, CV-40-Va-I inhibited the fibrin formation mediated by thromin, however the polysaccharide did not affect the fibrin formation directly but affected the anticoagulant activity through the activation of antithrombin III. The sulfation of the anticoagulant polysaccharide increased the anticoagulant activity, showing that the sulfate concentration of anticoagulant polysaccharide was important factor in the blood coagulation cascade. Low molecular weight subfraction (MW 1,000) obtained by partial hydrolysis of the CV-40-Va-1 generated potent antiplatelet activity, but showed decreased anticoagulant activity.

• Archives of Pharmacal Research
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• v.21 no.5
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• pp.549-554
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• 1998

Tissue factor (TF), a principal initiator of the veertebrate coagulation cascade, is expressed in organ tissues, cells and blood. TF is konwn to be induced in endothelial cells, monocytes and macrophages by inflammatory stimuli and in many pathologic conditions. By using the modified method for in vido TF activity assay, we found that turpentine oil injection as an inflamatory stimulus also induced the TF activity in lung and brain tissues of rats. And the age-related increase in Tf activity was observed in healthy rat brain tissue.

• Molecules and Cells
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• v.24 no.1
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• pp.125-131
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• 2007

von Willebrand factor (vWF) is a multimeric glycoprotein which functions within the coagulation system. It colocalizes with factor VIII (FVIII) by non-covalent interaction and alters its intracellular trafficking. vWF is also instrumental in maintaining the stability of secreted FVIII. The principal objective of this study was to generate a lentivirus-based vWF expression vector for gene therapy of hemophilia A. We inserted a vWF of 8.8 Kb into a lentiviral vector thereby producing VSV-G-pseudotyped vEx52. However, its titer was quite low, presumably because the length of vWF gene exceeds the size limit of the lentiviral vector. In order to overcome the low-titer, we concentrated the vEx52 and thus increased the efficiency of transduction approximately 6-fold with $1/100^{th}$ of the volume. However, as concentration requires an additional laborious step, we attempted to enhance the transduction efficiency by deleting exons 24-46 and 29-46 in pRex52 to construct pRex23 and pRex28, and in pvEx52, yielding pvEx23 and pvEx28, respectively. The transfected pRex52 had a profound effect on the activity of secreted FVIII, and this activity declined as domains of vWF were deleted. However, when the domain-deleted vWF-lentiviruses were transduced into K562 cells, the vEx28 increased the activity of the secreted FVIII compared to what was observed with vEx52. This result is probably due to higher efficiencies of transduction and expression while retaining the essential domains required for proper interaction with FVIII.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.189-189
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• 1998

Tissue factor (TF) is a cell surface receptor of coagulation factor Ⅶ and is the principal initiator of the vertebrate coagulation cascade. TF is found in high levels in some organs such as brain, lung and placenta, whereas blood monocytes, endothelial cells contain only trivial amount of TF when quiescent, and is stimulated to synthesize TF by infections or vascular lesions. TF is reported to be found in high levels in atherosclerotic plaques, cancer cells. TF activation in various cells in many infectious or immunologic diseases tells us the physiologic importance of TF. We screened many edible vegetables for TF inhibitor, by measuring the prothrombin time to detect the TF activity, and we picked Aster scaber to isolate the TF inhibitory substance. Aster scaber showed two kinds of anti thrombotic activity, one is TF inhibition and the other is elongation of plasma recalcification time. The anti thrombotic substances were found to be saponins which has echinocystic acid as aglycone.

• Journal of Microbiology and Biotechnology
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• v.18 no.3
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• pp.503-511
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• 2008

An edible marine red alga, Grateloupia filicina, collected from Jeju Island of Korea was hydrolyzed by cheap food-grade carbohydrases (Viscozyme, Celuclast, AMC, Termamyl, and Ultraflo) to investigate its anticoagulant activity. Among the tested enzymatic extracts of G. filicina, a Termamyl extract showed the highest anticoagulant activity. Anion-exchange chromatography on DEAE-cellulose and gel-permeation chromatography on Sepharose-4B were used to purify the active polysaccharide from the crude polysaccharide fraction of G. filicina. The purified sulfated polysaccharide (0.42 sulfate/total sugar) showed ${\sim}1,357kDa$ molecular mass and was comprised mainly of galactose(98%) and 1-2% of glucose. The sample showed potential anticoagulant activity on activated partial thromboplastin time (APTT) thrombin time (TT) assays. The purified G. filicina anticoagulant (GFA) inhibited the coagulation factor X (92%), factor II (82%), and factor VII (68%) of the coagulation cascade, and the molecular interaction (protein-polysaccharide) was highly enhanced in the presence of ATIII (antithrombin III). The dissociation constant of polysaccharide towards serine proteins decreased in the order of FXa (58.9 nM) >FIIa (74.6 nM) >FVII (109.3 nM). The low/less cytotoxicity of the polysaccharide benefits its use in the pharmaceutical industry; however, further studies that would help us to elucidate the mechanism of its activity are needed.

• Journal of Genetic Medicine
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• v.13 no.2
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• pp.89-94
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• 2016

Purpose: Molecular genetic analysis is the main approach used for prenatal diagnosis of hemophilia A and B. However, in certain cases, such analysis is uninformative. In such situations, direct measurement of fetal coagulation factor levels is still the best option, and it may be the only option in some cases. This study was conducted to determine the normal ranges of mid-trimester cord blood factor VIII (FVIII) and IX (FIX) in a Korean population. Materials and Methods: Twenty-six FVIII samples and 29 FIX samples were assayed in fetal cord blood acquired by ultrasound-guided cordocentesis. Sampling was conducted during gestational ages of 19-24 weeks. Results: The mean and standard deviations for FVIII and FIX activity were $45.5{\pm}30.5%$ and $19.9{\pm}12.2%$, respectively. Ranges for FVIII and FIX were 1.5-125.0% and 6.0-52.0%, respectively. Conclusion: Our study revealed the normal ranges and lowest level of factor VIII and factor IX in non-affected normal fetus by fetal cord blood sampling during the mid-trimester in a Korea population. The factor assay of the fetal cord blood is invasive but feasible and provides important basic data related to hemophilia.

• Korean Journal of Veterinary Service
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• v.34 no.2
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• pp.191-193
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• 2011

A 3-month-old intact male, Labrador retriever was presented with the history of coagulopathy and anemia. The results of initial screening tests of the hemostatic system yielded a tentative diagnosis of hemophilia. Activated partial thromboplastin time (APTT) was distinctly prolonged (106 seconds) and prothrombin time (PT) was not detected due to markedly prolonged test time. Whole blood transfusions (20 me l/kg body weight) were carried out prior to assays of coagulation factor. After transfusion, the patient recovered well and hemorrhage ceased. Blood samples were assessed for coagulation factor activity. The patient showed markedly low factor IX coagulation activity (5%, reference range: 7~140%) and was diagnosed with hemophilia B. After recovery, the patient was discharged from the hospital. However, 4 months later the patient was re-hospitalized for recurrence of the initial symptoms. The owner did not want to pursue further treatment and the patient died of respiratory distress two days later.

• The Journal of Internal Korean Medicine
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• v.16 no.1
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• pp.181-196
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• 1995

The present experiments were designed to investigate the effects of BangPoongSan on the cardiovascular system in the experimental Animals. And thus the change of blood pressure, auricular blood flow, artery contraction, death rate, platelet aggregation repression, plasma coagulation factor activity, plasma antithrombin activity, whole blood viscosity and plasma viscosity were studied. The result were summarized as the followings: 1. BangPoongSan dropped the blood pressure in the spontaneous hypertensive rat. 2. The drug increased the auricular blood flow in rabbit. 3. The drug relaxed the artery contraction by pretreated norepinephrine in white rat. 4. The drug inhibited the death rate of mouse which was led to thromboembolism by serotonin and collagen. 5. The drug inhibited the platelet aggregation in rat. 6. The drug prolonged the prothrombin time and activated partial thromboplastin time on the test of plasma coagulation factor activity in rat, but was not valuable. 7. The drug presented the antithrombin activity in rat. 8. The drug reduced the whole blood viscosity and plasma viscosity in rat, but the latter was not valuable. According to the results, Bangpoongsan increased the blood flow and dropped the blood pressure by dilatation of blood vessel smooth muscle. And the drug presented the antithrombin acivity, inhibited the platelet aggregation and reduced blood viscosity. Therefore these effects are assumed to improve the cardiovascular circulation disorder and prevent thrombosis.