• Journal of Life Science
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• v.20 no.11
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• pp.1640-1647
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• 2010

Seaweeds have been recognized as a health food, having anti-obesity, anti-constipation and anticoagulation activities, and the use of seaweeds in the food, medicine, and cosmetic industries have recently significantly increased. In this study, methanol extracts were prepared from 35 different seaweeds (17 phaeophyta, 11 rhodophyta and 7 chlorophyta), and thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (aPTT) were determined in order to develop safe and novel anticoagulation agents from natural products. In TT experiments, Ecklonia cava, Ecklonia stolonifera, Eisenia bicyclis (Kjellman) Setchell, Ishige foliacea, I. okamurai, Sargassum confusum and S. yamade showed strong thrombin inhibition activity among the 35 different seaweeds. In PT experiments, the inhibitions of prothrombin were identified in the selected seaweeds from TT experiment, with the exception of S. yamade. In aPTT experiments, the seaweeds with blood coagulation inhibition factors were E. cava, E. stolonifera, E. bicyclis (Kjellman) Setchell, I. foliacea, I. okamurai, S. confusum and Hixikia fusiforme Okamura. Further anticoagulation assay with the selected 8 seaweeds suggested that S. confusum is most effective in antithrombosis, and E. stolonifera, E. bicyclis (Kjellman) Setchell, and I. foliacea have high potential as antithrombosis agents. Based on components-activity correlation analysis, flavonoids are considered as active anticoagulation components of seaweeds These results suggest that edible seaweeds, especially S. confusum, have potential as safe and novel anticoagulants, and S. yamade and H. fusiforme Okamura could be used as a thrombin-specific and coagulation factor-specific inhibitors.

• Food Science and Preservation
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• v.24 no.5
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• pp.658-665
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• 2017

The current study was performed to investigate the changes of bio-activities of Salicornia europaea (SE) depending on the different dry methods. The ethanol extracts were prepared from the freeze-drying SE (FD), hot-air drying SE (HD), and shade drying SE (SD). Their anti-oxidant and anti-thrombosis activities were compared. The yields of ethanol extraction in FD, HD, and SD were 14.4, 13.2 and 11.9%, respectively. The highest contents of total polyphenol (4.6 mg/g) and total sugar (23.4 mg/g) were shown in FD, whereas, the highest content of reducing sugar (14.6 mg/g) was observed in HD. In anti-oxidation activity assay, the FD and HD showed similar radical scavenging activities and reducing power. However, in SD, nitrite scavenging activity and reducing power were severely decreased. In anti-coagulation activity assay, the thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (aPTT) of FD, HD and SD did not show significant changes at 5 mg/mL concentration. But the HD at 7 mg/mL had strong inhibitions against thrombin and blood coagulation factors. The platelet aggregation and hemolysis activities were not affected by dry methods. Our results suggest that both FD and HD are effective to maintain the functional ingredient of SE, and HD is economic and efficient dry process for production of functional food.

• Journal of Life Science
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• v.18 no.4
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• pp.427-434
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• 2008

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease and certain individuals are more at risk or may be predisposed to it. An altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. 3-hydroxy-3-methylglutaryl coenzyme A. (HMG-CoA) reductase inhibitors, stalin used as lipid-clearing agent, have been known to decrease the risk of osteonecrosis in patients receiving steroids and affect coagulation and fibrinolysis. Therefore we evaluated the association of HMG-CoA reductase gene polymorphisms and haplotypes between osteonecrosis patients and normal controls. We directly sequenced the HMG-CoA reductase gene in 24 Korean individuals, and identified five sequence variants. Four SNPs (-6933C>T, -6045T>G, +12673G>A, and +18128C>T) were selected and genotyped in 349 male ONFH patients and 300 male control subjects. The genotypes, allele frequencies, and haplotypes of the polymorphisms in the total patients as well as in the subgroup by etiology were not significantly different from those in the control group. In addition, no significant differences between each genotype of the polymorphisms and plasma lipid level could be found in the control group. These results suggest that the polymorphisms and haplotypes of HMG-CoA reductase gene are unlikely to be associated with a susceptibility to ONFH.

• Journal of Life Science
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• v.29 no.2
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• pp.164-172
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• 2019

In Korea, shiitake mushroom, Lentinula edodes, is cultivated on artificial medium containing oak sawdust and wheat bran. The annual production of spent mushroom substrate (SMS) of shiitake, a byproduct of the mushroom industry, is estimated to reach over 50,000 tons per year. This study aimed to improve the use of SMS as a novel bioresource. Hot water extracts of SMS after the first and third harvest were prepared and their bioactivities evaluated. Hot water extracts of uninoculated medium and shiitake were used as controls. Extracts of SMS showed higher radical scavenging of DPPH anions, ABTS cations, nitrites, and a higher reducing power than those of shiitake or medium extracts. After the first and third harvests at 0.5 mg/disc, SMS extracts showed no antibacterial or antifungal activities against the pathogenic and food-spoilage bacteria and fungi. However, they showed good inhibitory activities against ${\alpha}$-glucosidase at 0.5 mg/ml. In addition, SMS extracts had strong anti-coagulation activities via their inhibition of thrombin, prothrombin, and blood coagulation factors without platelet aggregation activity. Our results suggested SMS should no longer be perceived as a useless byproduct but should be understood as a novel bioresource, the extracts of which could be developed as antioxidant, antidiabetic, and antithrombosis agents.

• Journal of Life Science
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• v.32 no.4
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• pp.303-309
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• 2022

Dystaenia takesimana is an endemic plant found only in Korea, especially on Ulleung Island. The leaves and roots of D. takesimana have been used as food, forage, and oriental medicine. Anti-bacterial, anti-inflammation, antioxidant, and α-glucosidase inhibition biological activities have been reported in the plant's root extract. However, studies concerning the anti-thrombosis activities of D. takesimana are still in the rudimentary stage. In this study, the extracts of the leaf (DT-L), stem (DT-S), and root (DT-R) of D. takesimana were prepared using 70% ethanol, and their anti-thrombosis activities were evaluated. DT-L extracts (0.25 mg/ml) showed strong inhibitions against platelet aggregation, comparable to aspirin, with strong radical scavenging activities. Furthermore, the DT-L extract did not show any RBC hemolysis up to 1 m/ml. The ant-coagulation and antioxidant activities of the DT-S extract were ignorable. While the DT-R extract showed inhibitions against thrombin and blood coagulation factors, it also showed strong platelet aggregation. This is a first report of the anti-thrombosis activities of D. takesimana, and our results suggest that DT-L could be developed as a valuable bioresource for high value-added products.

• Journal of Life Science
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• v.34 no.3
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• pp.153-159
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• 2024

Dioscorea alata L, commonly known as "tropical yam" is the most widely consumed yam species among the 650 yam species belonging to the Dioscoreacea family. It is extensively cultivated in tropical and subtropical regions and is a major food source in Africa and India. Also, it is used for medicinal purposes, particularly in China and Taiwan, for its anti-inflammatory properties. In comparison to other yam varieties such as D. batatas or D. opposita, the tropical yam has gained popularity in Korea due to its higher yield per unit area. In this study, the nutritional characteristics and anti-thrombosis activity of the aerial bulbils of D. alata L. tropical yam were compared to those of D. opposita. The results showed that the aerial bulbils of tropical yam exhibited nutritional characteristics and potent anticoagulant activity compared to those of domestic yam varieties. The bulbils extract of tropical yam showed superior anticoagulant activities against thrombin, prothrombin and blood coagulation factors. Furthermore, the bulbils extract of tropical yam exhibited strong platelet aggregation inhibition at 0.25 mg/ml and showed no hemolytic activity up to a concentration of 2.5 mg/ml. These findings suggest the potential development of high-value anti-thrombosis agents utilizing the aerial bulbils of tropical yam.

• Journal of Chest Surgery
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• v.38 no.11 s.256
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• pp.746-760
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• 2005

Background: Following the implantation of heart valve prostheses, it is important to maintain therapeutic INR to reduce the risk of thromboembolism. The objectives of this study were to determine the causes of nontherapeutic INRs, and to identify the factors associated with nonadherences to warfarin therapy in Korean outpatients with prosthetic heart valves managed by a pharmacist-run anticoagulation service (ACS). Material and Method: A retrospective chart review was completed for all patients enrolled in the ACS at Seoul National University Hospital from March, 1997b to September, 2000. The data on 868 patients (5,304 visits) who were at least 6 months post-valve replacement were included. All possible causes of nontherapeutic INRs were documented for each patient visit. The association of covariates to noncompliance was investigated by univariate analysis. Result: The reasons for nontherapeutic INRs were identified as follows: inadequate dosage adjustment $(21\%)$, nonadherences to dosing regimen $(13\%)$, drug/herbal interactions $(12\%)$, changes in diet $(7\%)$, and indeterminate cause $(42\%)$. Younger age, shorter duration of ACS and longer duration of warfarin therapy were associated with nonadherence. Conclusion: In this study, nonadherence and interactions between diet and medications were found to be important factors influencing nontherapeutic INRs. Longer duration of enrollment in the ACS affected the adherence to warfarin therapy Positively whereas younger age and longer duration of warfarin therapy affected negatively.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.343-352
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• 2002

Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.

• Molecules and Cells
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• v.26 no.5
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• pp.490-495
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• 2008

Thrombophilia and hypofibrinolysis have been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Tissue factor pathway inhibitor (TFPI), a multivalent protease inhibitor, is an important regulator of the tissue factor-mediated blood coagulation pathway. Mutations of the TFPI gene can increase the risk of thrombin generation and venous thrombosis. The aim of this study was to evaluate the association of TFPI gene polymorphisms with ONFH. All exons and their boundaries of the TFPI gene, including the -1,500 bp promoter region, were directly sequenced in 24 Korean individuals and four sequence variants were identified. These four polymorphisms [-51096 G > A (C-399T), -50984A > G (T-287C), + 24999A > G (Int7 -33T > C), + 37339T > A] were genotyped in 474 ONFH patients and 349 control subjects. The association of genotyped SNPs with ONFH was not found in the present study. The haplotype AAAT of TFPI was significantly associated with total, alcohol-induced, and idiopathic ONFH (p = 0.003, 0.021, and 0.007, respectively), and the haplotype GAAT was significantly associated with total and alcohol ONFH (p = 0.022 and 0.009, respectively). In addition, a new SNP + 37339 T > A in the 3'-UTR of the TFPI gene, was found in the Korean population. To date, this study is the first to show that haplotypes of the TFPI gene are associated with an increased susceptibility for ONFH. The results suggest that genetic variations in TFPI may play an important role in the pathogenesis and risk factors of ONFH.

• Tuberculosis and Respiratory Diseases
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• v.73 no.4
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• pp.231-233
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• 2012

Tadalafil is a phosphodiesterase-5 inhibitor (PDE5I), which is widely used to treat erectile dysfunction. Although PDE5Is have excellent safety profiles, and most of the side effects are mild, rare serious adverse events have been reported in association with PDE5Is. Thrombosis is one of those events, and a few previous reports have suggested the association of PDE5Is with thrombosis. We report the case of a 61-year-old male who developed pulmonary embolism combined with pulmonary infarction directly after taking tadalafil. Both the patient and the physician suspected tadalafil as the culprit drug, as the patient was in an otherwise healthy condition. However, after extensive evaluation, we noticed that factor VIII levels were elevated. Prior reports suggesting the association between thrombosis and PDEIs either lack complete information on coagulation factors, or show inconsistencies in their results. Physicians should operate caution prior to accepting the diagnosis of adverse drug reaction.