• Title/Summary/Keyword: hemostasis

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Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation

  • Jeong, Dahye;Irfan, Muhammad;Kim, Sung-Dae;Kim, Suk;Oh, Jun-Hwan;Park, Chae-Kyu;Kim, Hyun-Kyoung;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.41 no.4
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    • pp.548-555
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    • 2017
  • Background: Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. Methods: To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ($[Ca^{2+}]_i$) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. Results: We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and $[Ca^{2+}]_i$ mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. Conclusion: These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.

Effects of mixture of fibrin-fibronectin sealant system and calcuim carbonate in periodontal intrabony defects (calcium carbonate와 fibrin-fibronectin sealant system 혼합이식이 치주골내낭 치유에 미치는 영향)

  • Chang, Soo-Jin;Han, Dong-Kwan;Yun, Jeong-Ho;Jung, Ui-Won;Kim, Chang-Sung;Choi, Seong-Ho;Cho, Kyoo-Sung;Kim, Chong-Kwan;Chai, Jung-Kiu
    • Journal of Periodontal and Implant Science
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    • v.34 no.3
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    • pp.581-591
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    • 2004
  • Calcium carbonate(CC) is biocompatible and gradually absorb to be replaced by bone when implanted into bone tissue. Fibrin-fibronectin sealant system (FFSS) is a product of human-derived plasma. The effect is hemostasis, tissue fixation and adhesion, We expect synergic effects of this two materials in periodontal regeneration. When FFSS was grafted with bone graft in intrabony defects, could be eliminated exofolication of bone graft materials. This study evaluated above materials for periodontal regeneration of 6mm intrabony defects in 36 patients. lap surgery was carried in 14 defects of control group. experimental group 1 was 11 defects grafted with calcium carbonate, experimental group 2 was 11 defects which were grafted with calcium carbonate with FFSS. The clinical parameters evaluated included changes in attachment level, probing depth, gingival recession at 6 months. Postsurgery probing depth reduction was 3.1 ${\pm}$ 0.9mm in control, 3.8 ${\pm}$ 1.6mm in experimental group 1, 4.1 ${\pm}$ 1.1mm in experimental group 2. The result clinically and statistically improved compared to baseline(P<0.01), but the difference found among the groups were not statistically significant. Postsurgery clinical attachment level was 1.6 ${\pm}$ 1.2mm in control, 3.5 ${\pm}$ 2.0mm in experimental group 1, 3.3 ${\pm}$ 1.2mm in experimental group 2. All of the control and experimental groups resulted in a statistically significant reduction from baseline(P<0.01). The reduction of the experimental groups were statistically significant from control(P<0.05). But the change between experimental group 1 and experimental group 2 was not statistically significant. We conclude that mixture of CC and FFSS is effective to periodontal regeneration in intrabony defect.

Effects of Olibanum Extracts on the Activity and Differentiation of MC3T3-E1 Cells (유향 추출물이 MC3T3-E1 세포 활성 및 분화에 미치는 영향)

  • Han, Sang-Heon;Kim, Myoung-Dong;You, Seung-Han;You, Yong-Ouk;You, Hyung-Keun;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.31 no.2
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    • pp.287-298
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    • 2001
  • Recently, many natural medicines, which have advantage of less side effects and possibility of long-term use have been studied for their capacity of anti-bacterial, anti-inflammatory and regenerative potential of periodontal tissues. Olibanum has the effects to hemostasis, analgesic and anti-inflammatory, and it also has been traditionally used as a drug for the treatment of bone disease in oriental medicine. The purpose of the present study was to investigate the effects of Olibanum extracts on the activity and differentiation of MC3T3-E1 cells, alkaline phosphatase(ALP) synthesis, formation of bone nodules and expression of type I collagen of MC3T3-E1 cells. To examine the cellular activity, MC3T3-E1 cells were cultured with ${\alpha}-MEM(control)$ and each concentration of Olibanum for 2 days and 4 days. To compare the ALP synthesis, MC3T3-E1 cells were cultured with ${\alpha}-MEM(negative\; control)$, dexamethasone(positive control), and each concentration of Olibanum for 2 days and 4 days. To compare the bone nodule formation, MC3T3-E1 ells were cultured for 21 days, and to compare the type I collagen expression, MC3T3-E1 cells were cultured for 4 days. The cellular activity of MC3T3-E1 cells treated with $1{\mu}g/ml$ of Olibanum extracts was significantly increased at 4-day(p<0.05) to control. The activity of ALP in MC3T3-E1 cells treated with $1{\mu}g/ml$ Olibanum extracts was significantly increased at 4-day(p<0.05). All the experimental groups showed much more bone nodule formation than control groups. The group treated with $1{\mu}g/ml$ of Olibanum extracts was the highest bone nodule formation, and showed much more type I collagen expression than negative control. These results indicate that Olibanum extracts may be considered effective in the activity and differentiation of MC3T3-E1 cells.

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Dabigatran Toxicity Secondary to Acute Kidney Injury (급성신손상으로 인해 발생한 dabigatran 독성)

  • Moon, Hyoung Ho;Lee, Seung Eun;Oh, Dong Jun;Jo, Hee Bum;Kwon, Ki Hwan;Kim, Yoon Jin;Kim, Kyung Soo;Shin, Sung Joon
    • Journal of The Korean Society of Clinical Toxicology
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    • v.12 no.2
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    • pp.92-96
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    • 2014
  • Dabigatran is the first oral direct thrombin inhibitor approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Because dabigatran is excreted mainly by the kidneys, serum levels of dabigatran can be elevated to a supratherapeutic range in patients with renal failure, predisposing to emergent bleeding. We describe the case of a 66-year-old man taking dabigatran 150 mg twice daily for atrial fibrillation and cerebral infarction who presented with hematochezia and disseminated intravascular coagulation. Laboratory evaluation showed a hemoglobin level of 6.3 g/dL, platelets of $138,000/mm^3$, activated partial thromboplastin time (aPTT) of 10 s, and an international normalized ratio (INR) of 8.17. Colonoscopy showed a bleeding anal fissure. Hemostasis was provided by hemoclips and packed red blood cells and fresh frozen plasma were transfused. Since then, there was no further hematochezia, however, bleeding including oral mucosal bleeding, hematuria, and intravenous site bleeding persisted. At presentation, his serum creatinine was 4.96 mg/dL (baseline creatinine, 0.9 mg/dL). Dabigatran toxicity secondary to acute kidney injury was presumed. Because acute kidney injury of unknown cause was progressing after admission, he was treated with hemodialysis. Fresh frozen plasma transfusion was provided with hemodialysis. At 15 days from admission, there was no further bleeding, and laboratory values, including hemoglobin, partial thromboplastin time, and prothrombin time were normalized. He was discharged without bleeding. After 2 months, he undergoes dialysis three times per week and no recurrence of bleeding has been observed.

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Effect of a Hot Water Extract of Sparasis Crispa on the Expression of Tight Junction-Associated Genes in HaCaT Cells (꽃송이버섯 열수추출물이 HaCaT의 세포 연접 관련 유전자의 발현에 대한 영향)

  • Han, Hyo-Sang
    • Journal of The Korean Society of Integrative Medicine
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    • v.9 no.2
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    • pp.83-92
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    • 2021
  • Purpose : Keratinocytes are the main cellular components involved in wound healing during re-epithelization and inflammation. Dysfunction of tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. The purpose of this study was to identify the various effects of a Sparassis crispa water extract (SC) on HaCaT cells and to investigate whether these effects might be applicable to human skin. Methods : We investigated the effectiveness of SC on cell HaCaT viability using MTS. The antioxidant effect of SC was analyzed by comparing the effectiveness of ABTS to that of the well-known antioxidant resveratrol. Reverse-transcription quantitative polymerase chain reaction (qRT-PCR) is the most widely applied method Quantitative RT-PCR analysis has shown that SC in HaCaT cells affects mRNA expression of tight-junction genes associated with skin moisturization. In addition, Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis, inflammation, growth, re-epithelialization, and remodeling. wound healing analysis demonstrated altered cell migration in SC-treated HaCaT cells. Results : MTS analysis in HaCaT cells was found to be more cytotoxic in SC at a concentration of 0.5 mg/㎖. Compared to 100 µM resveratrol, 4 mg/㎖ SC exhibited similar or superior antioxidant effects. SC treatment in HaCaT cells reduced levels of claudin 1, claudin 3, claudin 4, claudin 6, claudin 7, claudin 8, ZO-1, ZO-2, JAM-A, occludin, and Tricellulin mRNA expression by about 1.13 times. Wound healing analysis demonstrated altered cell migration in SC-treated HaCaT cells and HaCaT cell migration was also reduced to 73.2 % by SC treatment. Conclusion : SC, which acts as an antioxidant, reduces oxidative stress and prevents aging of the skin. Further research is needed to address the effects of SC on human skin given the observed alteration of mRNA expression of tight-junction genes and the decreased the cell migration of HaCaT cells.

Maintenance of Platelet Counts with Low Level QC Materials and the Change in P-LCR according to Hemolysis with XN-9000 (XN-9000장비에서 Low Level QC물질에서의 혈소판 수 관리와 용혈에 따른 P-LCR의 변화)

  • Shim, Moon-Jung;Lee, Hyun-A
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.399-405
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    • 2018
  • The platelet count in clinical laboratories is essential for the diagnosis and treatment of hemostasis abnormalities, and accurate platelet counting in the low count range is of prime importance for deciding if a platelet transfusion is needed and for monitoring after chemotherapy. Quality control is designed to reduce and correct any deficiencies in the internal analytical process of a clinical laboratory prior to the release of patient results. Fragmented erythrocytes are the major confusing factors for platelet counting because of their similar size to platelets. The authors found that the low range QC values were out of 2SD with a Sysmex automatic analyzer in internal quality control process. Thus far, there has been little discussion on the relationship between hemolysis and the platelet parameters. Therefore, this study focused on the performance of automated platelet counts, including the PLT-F, the PLT-I, and PLT-O methods at the low platelet range using the low level QC materials and compared the 5 platelet parameters with the hemolyzed samples. The results showed that the CV was the smallest with PLT-F and P-LCR increased from 18.4 to 31.9% in the hemolysis samples. These results indicate that a more accurate estimation of the platelet counts can be achieved using the PLT-F method than the PLT-I method at the low platelet range. The use of the PLT-F system improves the confidence of results in low platelets samples in a routine hematology laboratory. The results suggest that P-LCR is a new parameter in assessing samples when the specimen is suspected of hemolysis and deterioration. Nevertheless, further studies will be needed to establish the relationship with P-LCR and hemolysis using human blood specimens.

Anti-oxidation and Anti-thrombosis Activities of Polyphenol-enriched Fraction of Acorn Pollen Extract (도토리 화분 추출물의 폴리페놀 고함유 분획물의 항산화 및 항혈전 활성)

  • Lee, Yun-Jin;Kang, Deok-Gyeong;Pyo, Su-Jin;Sohn, Ho-Yong
    • Journal of Life Science
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    • v.32 no.7
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    • pp.501-509
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    • 2022
  • Pollen corrected from Quercus species is abundant in Korea and has been used to treat anemia and inflammation of the prostate gland. It is also used for hemostasis in oriental medicine. In this study, the ethanol extract of the acorn pollen and its subsequent organic solvent fractions using hexane, ethylacetate, butanol, and water residue were prepared, and their antioxidant, anti-thrombosis, and hemolysis activities were evaluated. The ethylacetate fraction of acorn pollen (EF-AP) showed the highest polyphenol content (225.0 mg/g) and strong antioxidant activity among the solvent fractions. The RC50 of EF-AP against DPPH, ABTS, and nitrite radicals was 72.2, 27.7, and 62.6 ㎍/ml, respectively. The blood coagulation activities of the all-solvent fractions determined by thrombin time, prothrombin time, and activated partial thromboplastin time were negligible up to 5 mg/ml. Platelet aggregation inhibitory activities were observed in the EF-AP, butanol fraction, and water residue, whereas hexane fraction induced strong platelet aggregation. The EF-AP has no hemolysis activity against human RBC up to 1 mg/ml. UPLC/MS/MS analysis of the EF-AP revealed that rutin, isoquercitrin, and astragalin are major compounds for antioxidant and anti-thrombosis activities. Our results suggest that EF-AP could be developed as a noble antioxidant and anti-thrombosis agent.

Anti-inflammatory Effects of Ethanol Extract of Korean Medicinal Plants at Hwaak Mountain in LPS-induced RAW 264.7 Macrophages

  • Kang, Yun-Mi;Jeon, Eun-jin;Chung, Kyung-Sook;Cheon, Se-Yun;Park, Jong Hyuk;Han, Yoo-Chang;An, Hyo-Jin
    • The Korea Journal of Herbology
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    • v.32 no.2
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    • pp.25-32
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    • 2017
  • Objectives : This study was conducted to investigate candidate materials as anti-inflammatory agent from extracts of Korean medicinal plants in Hwaak mountain. Ligustrum obtusifolium (LO) is a Korea medicinal plants that commonly used for robustness and hemostasis. It has been reported that LO has exhibited anti-ischemic, anti-oxidative, anti-hypolipidemic, anti-tumor and hypoglycemic effects. However, LO has not been previously reported to have an anti-inflammatory effect. Therefore, we have evaluated the anti-inflammatory effects of LO and its underlying molecular mechanisms in LPS-induced RAW 264.7 macrophages. Methods : Cell viability was determined by MTT assay in RAW 264.7 macrophages. Nitric Oxide (NO) was measured with Griess reagent and pro-inflammatory cytokines were detected by ELISA in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and p65 subunit of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) were determined by Western blot analysis. Results : Among 15 extracts of Korean medicinal plants tested, Ligustrum obtusifolium (LO) showed the inhibition of NO production without cytotoxicity. LO reduced the expression levels of iNOS and COX-2 proteins in LPS-simulated RAW 264.7 macrophages in dose-dependent manner. Consistent with these data, LO inhibited the productions of $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$ in LPS-simulated RAW 264.7 macrophages. Furthermore, LO attenuated the LPS-induced nuclear translocation of p65 $NF-{\kappa}B$ in RAW 264.7 macrophages involving suppression of $NF-{\kappa}B$ activation. Conclusions : Taken together, these results suggest that the anti-inflammatory effects of LO is associated with regulation of inflammatory mediators via inhibition of $NF-{\kappa}B$ activation in LPS-treated RAW 264.7 macrophages.

Inhibitory effects of artemether on thrombus formation via regulation of cyclic nucleotides in collagen-induced platelets (콜라겐-유도의 혈소판에서 사이클릭 뉴클레오티드의 조절을 통한 Artemether의 항혈전 효과)

  • Chang-Eun Park;Dong-Ha Lee
    • Journal of Applied Biological Chemistry
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    • v.65 no.4
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    • pp.239-245
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    • 2022
  • Although normal activation of platelets is important in the process of hemostasis, excessive or abnormal activation of platelets can lead to cardiovascular diseases. Therefore, the discovery of novel substances capable of regulating or inhibiting platelet activation may be helpful in the prevention and treatment of cardiovascular diseases. Artemether is a derivative of artemisinin, known as an active ingredient of Artemisia annua, which has been reported to be effective in treating malaria, and is known to function through antioxidant and metabolic enzyme inhibition. However, the role of artemether in platelet activation and aggregation and the mechanism of action of artemether in collagen-induced human platelets are not known until now. This study investigated the effects of artemether on platelet activation and thrombus formation induced by collagen. As a result, cAMP level was significantly increased by artemether, and VASP and IP3R, substrates of cAMP-dependent kinase, were phosphorylated. IP3R phosphorylation by Artemether inhibited Ca2+ recruitment into the cytoplasm, and phosphorylated VASP inhibited fibrinogen binding by inactivating αIIb/β3 located on the platelet membrane. Consequently, artemether inhibited thrombin-induced fibrin clot formation. Therefore, we propose that artemether can act as an effective prophylactic and therapeutic agent for cardiovascular diseases caused by excessive platelet activation and thrombus formation.

Behavior of Heavy Metals Studies on the Hydrothermal Alteration Characteristics of Bentonite; Use as Medicinal Mineral (벤토나이트의 열수변질특성에 따른 중금속의 거동 특성 : 광물성 약재로의 활용)

  • Seon-ok Kim;Sookyun Wang
    • Economic and Environmental Geology
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    • v.56 no.3
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    • pp.229-238
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    • 2023
  • Bentonite is a type of rock that has been used as a traditional mineral medicine. It has a variety of pharmacological activities, and is used in traditional Korean medicine to treat jaundice, diarrhea, and hemostasis. In modern medicine, it is used as a raw material and additive for medicines such as antacids, gastrointestinal protective agents, and laxatives. Bentonite produced in Korea was produced through diagenesis or hydrothermal alteration of tertiary volcanic debris distributed in the Pohang and Gyeongju areas. It is mainly used for industrial purposes such as papermaking, paint, civil engineering, casting, and animal feed. Recently, technology is being developed to use it in cosmetics and pharmaceuticals. In this study, the geochemical characteristics of bentonite were identified by analyzing the main components and trace elements of 40 and 21 types of bentonite produced in the Gampo Gyeongju and Yeonil Pohang area. Also it were classifed by formation envrionment of bentonite deposits in the Gampo and Yeonil. As a result of the study, bentonite from the reserch area may be cased by argillic alteraton that alkali elements are removed form basaltic rocks by hydrothermal fluids and AI-CCPI alteration indices wrere also indentified argillic alteraton. It was found that there is a correlation between the behavior characteristics of heavy metal elements (P b, Cr, As) and the hydrothermal alteration of bentonite in the reserch area.