• Applied Biological Chemistry
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• v.42 no.4
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• pp.336-343
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• 1999

Fifty six mycelial cultured Basidiomycetes were screened for their inhibitory effects against prolyl endopeptidase(PEP), acetylcholine esterase(AChE) and thrombus coagulation. Out of them, methanolic extract of mycelium and/or ethylacetate(EtOAc) soluble fraction from culture broth of Peniophora quercina, Amanita aspera, Phellinus chrysoloma, Grifola frondosa, Wolfiporia extensa, Clavicorona pyxidata and Phanerochaete sordida inhibited more than 90% of PEP activity at 40 ppm. The extracts of Lenzites betulina, Phellinus chrysoloma, Wolfiporia extensa, Phanerochaete sorrlida, Hypocrea nigricans, Coriolus azureus, Flammulina velutipes, Phlebiopsis gigantea and Bondarzewia montana exhibited about 40% of inhibitory activity against AChE at 40 ppm. In thrombin times assay, the extracts of Amanita aspera, Oxyporus latemarginata, Peniophora quercina, Fomes fomenfarius, Trametes versicolor, and Phlebiopsis gigantea delayed coagulation of thrombus about two to three times over control at ca 550 ppm. In activated partial thromboplastin times assay, none of the tested Basidiomycetes showed significant effect.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6275-6281
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• 2014

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received $2500IU/m^2$/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4529-4532
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• 2013

Background: Acute normovolemic hemodilution (ANH) has been widely used to prevent the massive blood loss during hepatic carcinoma. The influences of ANH on coagulation function are still controversy, especially in elderly patients. The study observed ANH effects on coagulation function and fibrinolysis in elderly patients undergoing the disease. Materials and Methods: Thirty elderly patients (aged 60-70 yr) with liver cancer (ASA I or II) taken hepatic carcinectomy from February 2007 to February 2008 were randomly divided into ANH group (n=15) and control group (n=15). After tracheal intubation, patients in ANH group and control group were infused with 6% hydroxyethyl starch (130/0.4) and Ringer's solution, respectively. Blood samples were drawn from patients in both groups at five different time points: before anesthesia induction (T1), 30 min after ANH (T2), 1 h after start of operation (T3), immediately after operation (T4), and 24 h after operation (T5). Then coagulation function, soluble fibrin monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (CD62P and activated GP IIb/GP IIIa) were measured. Results: The perioperative blood loss and allogeneic blood transfusion were recorded during the surgery. The perioperative blood loss was not significantly different between two groups (p>0.05), but the volume of allogeneic blood transfusion in ANH group was significantly less than in control group ($350.0{\pm}70.7$) mL vs. ($457.0{\pm}181.3$) mL (p<0.01). Compared with the data of T1, the prothrombin time (PT) and activated partial thromboplastin time (APTT) measured after T3 were significantly longer (p<0.05) in both groups, but within normal range. There were no significant changes of thrombin time (TT) and D-dimer between two groups at different time points (p>0.05). SFMC and F1+2 increased in both groups, but were not statistically significant. PAC-1-positive cells and CD62P expressions in patients of ANH group were significantly lower than those at T1 (p<0.05) and T2-T5 (p>0.05). Conclusions: ANH has no obvious impact on fibrinolysis and coagulation function in elderly patients undergoing resection of liver cancer. The study suggested that ANH is safe to use in elderly patients and it could reduce allogeneic blood transfusion.

• Journal of Ginseng Research
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• v.31 no.2
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• pp.109-116
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• 2007

Korean red ginseng has broad efficacious effects against hypertension, diabetes, nociception, and cancer, and it counteracts weakness. It has been reported that Korean red ginseng is able to normalize blood pressure, improve cholesterol and lower blood glucose levels. We have recently reported that Korean red ginseng extract (KRGE) significantly prevented rat carotid arterial thrombosis in vivo, and inhibited platelet aggregation ex vivo and in vitro in a dose-dependent manner. The purpose of this study was to examine the effects of KRGE on blood circulation in human by measuring ex vivo platelet aggregation, plasma coagulation and serum lipid profiles in healthy volunteers. Subjects were randomly divided into three groups (placebo-group, KRGE-low dose group, KRGE-high dose group). Administration of KRGE to subjects significantly inhibited ADP-induced platelet aggregations both in KRGE-low dose group from $72.79{\pm}20.53$ to $62.00{\pm}23.06%$ (p=0.0009), and in KRGE-high dose group from $75.14{\pm}21.86$ to $64.52{\pm}24.72%$ (p=0.0039), respectively. Administration of KRGE to subjects also significantly inhibited collagen-induced platelet aggregations both in KRGE-low dose group from $85.52{\pm}12.57$ to $79.62{\pm}20.47%$ (p=0.0916), and in KRGE-high dose group from $80.24{\pm}18.11$ to $70.31{\pm}25.93%$ (p=0.0565), respectively. Whereas, KRGE has no significant effects on coagulation system, such as prothrombin time (PT) and activated partial thromboplastin time (APTT), and serum lipid profiles, such as total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride. KRGE also has no significant effects on hematological and serum biochemical profiles. These results suggest that KRGE has a potential to improve blood circulation through antiplatelet activity in human, and KRGE intake may be beneficial for the individuals with high risks of thrombotic and cardiovascular diseases.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.898-903
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• 2006

The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its anti platelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with $IC_{50}$ values of $620{\pm}12$, $823{\pm}22$, $722{\pm}21$ and $650{\pm}14\;{\mu}g/mL$, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.3
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• pp.110-126
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• 2005

Purpose : The Purpose of this research was to investigate the effects of antithrombotic activities of Wuslsan (WSS). Methods : Measure the effect which was given to blood flow rate through the regular volume of glass tube after the blood was diluted five times with ACD soulution. Antithrombotic effect was calculated as a percentage of the experimental animal figure protected from the paralysis of hind legs or death of the mouse that is caused from the administration of platelet aggregation regent. Being classified one group of eight mice, each of them was divided into Normal, Control, and WSS. The normal group supplied a saline solution and the control group brought the dextran extravasated blood after an hour of administering the saline solution. Also WSS was dissolved in 2ml saline solution and then we dosed it to the experimental mice with Oral Zonde one day before the experiment. After that, the mice were abstained from food. And then we gave a measured amount of it before an hour. Finally, it gave rise to dextran extravasated blood in the same way as the Control group. Results : The results were obtained as follows. WSS inhibited platelet aggregation induced by ADP and epinephrine significantly as compared with the control group. WSS showed fibrinolytic activity insignificantly as compared with the control group. WSS increased blood flow rate significantly as compared with the control group in vitro. WSS inhibited pulmonary embolism induced by collagen and Epinephrine(inhibitive rate is 37.5%). WSS increased number of platelet and fibrinogen amount significantly, and shortened PT and APTT as compared with the control group in thrombus model induced by dextran. Conclusion : WSS is effective antithrombotic activity from experimental result.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.1
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• pp.1-14
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• 2005

This study was performed to evaluate antithrombotic activities of Saegeumsan (瑞金散, SGS) which has effects of activating blood, removing thrombus. This study is designed to measure the effect which was given to blood flow rate through the regular volume of glass tube after the blood was diluted five times with ACD solution. Antithrombotic effect was calculated as a percentage of the experimental animal figure protected from the paralysis of hind legs or death of the mouse that is caused from the administration of platelet aggregation regent. We standardized the time when the experimental animals were incapable of functioning the hind legs more than 20 minutes or maintained trembling. Being classified one group of eight mice, each of them was divided into Normal, Control, and SGS. The normal group supplied a saline solution and the control group brought the dextran extravasated blood after an hour of administering the saline solution. Also, SGS was dissolved in $2m{\ell}$ saline solution and then we dosed it to the experimental mice with Oral Zonde one day before the experiment. After that, the mice were abstained from food. And then we gave a measured amount of it before an hour. Finally, it gave rise to dextran extravasated blood in the same way as the Control group. The results were obtained as follows, SGS significantly inhibited platelet aggregation induced by ADP and epinephrine when analyzed by the Sigmoid $E_{max}$ model in WinNonlin. $EC_{50}$ values of SGS were 4.61 mg/ml and 12.41 mg/ml for ADP and epinephrine respectively. SGS showed fibrinolytic activity insignificantly as compared with the control group. SGS increased blood flow rate significantly as compared with the control group in vitro. SGS inhibited pulmonary embolism induced by collagen and epinephrine(inhibitive rate is 37.5 %). SGS increased number of platelet and fibrinogen amount significantly, and shortened PT and APTT as compared with the control group in thrombus model induced by dextran. According to, SGS is effective antithrombotic activity from experimental result.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.152-166
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• 2014

Purpose: The purpose of this study is to compare with the result of experimental study about antithrombotic effect by reviewing recent oriental medicine journals that have been published since 2001' in Korea. Methods: Articles on antithrombotic effect that have been published from 2001' to 2013' in oriental medicine journals registered National Research Foundation of Korea were searched. After that, 12 articles using same 'thrombosis condition model' were selected and reviewed. Results: The results were as follows. 1. If there is no limit drug concentrations, platelet aggregation induced by adenosine diphosphate (ADP) in hyulbuchukeo-tanggamibang (HBCT) was the largest aggregation inhibitory effect and platelet aggregation induced by epinephrine in Saegeum-san (SGS), Jogan-tanggagambang (JGTG), hyulbuchukeo-tanggamibang (HBCT) had a large inhibitory effect on aggregation. 2. At the lowest concentration, Mokdan-san (MDS) of the inhibition of platelet aggregation induced by ADP and Hyunhosaik-san (HHS) of the inhibition of platelet aggregation induced by epinephrine were effective. 3. Pulmonary embolism induced by collagen and epinephrine in Neungasojeok-tang (NSJT) has the highest antithrombotic effect. 4. Pathological conditions of extravasated blood by dextran, Jogan-tanggagambang (JGTG) has the highest inhibitory effect on decrease in platelet numbers. Compared to the rest of the experimental drug, Saegeum-san (SGS), Heanggyonghonghwa-tang (HGTHHT), Wusl-san (WSS), Mokdan-san (MDS) showed significant inhibitory effect on the prothrombin time (PT) increases. Honghwadanggui-san (HDS), Saegeum-san (SGS) showed significant inhibitory effect on increase in activated partial thromboplastin time (APTT) and Jogan-tanggagambang (JGTG), Heanggyonghonghwa-tang (HGTHHT) showed significant inhibitory effect on decrease in fibrinogen. Conclusions: This result will provide useful information for the prescriptions of antithrombotic medicine in the field of Oriental medicine. We will have to carry out further studies that will compare each herb used in the diseases caused by extravasated blood.

• Food Engineering Progress
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• v.14 no.4
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• pp.359-366
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• 2010

Large-scale preparation steps of antithrombotic materials from wood ear mushroom (Auricularia auricular-judae) were established as follows. Grounded dry wood ear mushroom was extracted with 75% ethanol and its precipitate was extracted with $76^{\circ}C$ water for 2 hr followed by filter pressing. The filtrate was then concentrated by vacuum and extracted with 80% ethanol, and the resulting precipitate was then freeze-dried. The formula of the product was determined using consumer susceptibility tests as follows; mushroom extract 90.5%, high fructose corn syrup 2.0%, $\beta$-cyclodextrin 1.5%, fructo-oligosaccharide 2.0%, pear puree 4.0%. When the packed products were stored at 25, 37, or $45^{\circ}C$ for 8 weeks, there were no noticeable changes in water activity, moisture content, pH, and acidity. The viable cell number of total bacteria was slightly increased during the storage period at 25 and $37^{\circ}C$, The total bacteria were not detected in the product when stored at $45^{\circ}C$. When the product was injected intravenously into rat at the level of 1,000 mg/kg, antithrombotic activities such as activated partial thromboplastin time, thrombin time, prothrombin time, and FIB were increased when compared with the control group. When the product was administrated orally into rat at the level of 500 mg/kg, it showed the same antiplatelet activity to aspirin.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.56-78
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• 1998

Objective: Chronic hepatitis B infection (CHB) occurs in 6% to 10% of population in Korea. In ethinic communities where prevalence of chronic infection is high such as Korea, transmission of hepatitis B infection is either vertical (ie, by perinatal infection) or by close family contact (usually from mothers or siblings) during the first 5 years of life. The development of chronic hepatitis B infection is increasingly more common the earlier a person is exposed to the virus, particularly in fetal and neonatal life. And it progress to cirrhosis and hepatocellular carcinoma, especially in severe liver damage and perinatal infection. Histopathology of CHB is important when evaluating the final outcomes. A numerical scoring system which is a semiquantitatively assessed objective reproducible classification of chronic viral hepatitis, is a valuable tool for statistical analysis when predicting the outcome and evaluating antiviral and other therapies. In this study, a numerical scoring system (Ludwig system) was applied and compared with the conventional histological classification of De Groute. And the comparative analysis of cinical findings, family history, serology, and liver function test by histopathological findings in chronic hepatitis B of children was done. Methods: Ninety nine patients [mean age=9 years (range=17 months to 16 years)] with clinical, biochemical, serological and histological patterns of chronic HBV infection included in this study. Five of these children had hepatocelluar carcinoma. They were 83 male and 16 female children. They all underwent liver biopsies and histologic evaluation was performed by one pathologist. The biopsy specimens were classified, according to the standard criteria of De Groute as follows: normal, chronic lobular hepatitis (CLH), chronic persistent hepatitis (CPH), mild to severe chronic active hepatitis (CAH), or active cirrhosis, inactive cirrhosis, hepatocellular carcinoma (HCC). And the biopsy specimens were also assessed and scored semiquantitatively by the numerical scoring Ludwig system. Serum HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc (IgG, IgM), and HDV were measured by radioimunoassays. Results: Male predominated in a proportion of 5.2:1 for all patients. Of 99 patients, 2 cases had normal, 2 cases had CLH, 22 cases had CPH, 40 cases had mild CAH, 19 cases had moderate CAH, 1 case had severe CAH, 7 cases had active cirrhosis, 1 case had inactive cirrhosis, and 5 cases had HCC. The mean age, sex distribution, symptoms, signs, and family history did not differ statistically among the different histologic groups. The numerical scoring system was correlated well with the conventional histological classification. The histological activity evaluated by both the conventional classification and the scoring system was more severe as the levels of serum aminotransferases were higher. In contrast, the levels of serum aminotransferases were not useful for predicting the degree of histologic activity because of its wide range overlapping. When the histological activity was more severe and especially the cirrhosis more progressing, the prothrombin time was more prolonged. The histological severity was inversely related with the duration of seroconversion of HBeAg. Conclusions: The histological activity could not be accurately predicted by clinical and biochemical findings, but by the proper histological classification of the numerical scoring system for the biopsy specimen. The numerical scoring system was correlated well with the conventional histological classification, and it seems to be a valuable tool for the statistical analysis when predicting the outcome and evaluating effects of antiviral and other therapies in chronic hepatitis B in children.