• Title/Summary/Keyword: Anti-thrombotic

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Recurrent hemolytic uremic syndrome caused by DGKE gene mutation: a case report

  • Shin, Baek Sup;Ahn, Yo Han;Kang, Hee Gyung
    • Childhood Kidney Diseases
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    • v.26 no.1
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    • pp.58-62
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    • 2022
  • Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury without any association with preceding diarrhea. Dysregulation of the complement system is the most common cause of aHUS, and monoclonal humanized anti-C5 antibodies are now recommended as the first-line treatment for aHUS. However, if the complement pathway is not the cause of aHUS, C5 inhibitors are ineffective. In this study, we report the second reported case of aHUS caused by DGKE mutations in Republic of Korea. The patient was an 11-month-old infant who presented with prodromal diarrhea similar to typical HUS, self-remitted with conservative management unlike complement-mediated aHUS but recurred with fever. While infantile aHUS often implies genetic dysregulation of the complement system, other rare genetic causes, such as DGKE mutation, need to be considered before deciding long-term treatment with C5 inhibitors.

Cytokinetic Study of MCF-7 Cells Treated with Commercial and Recombinant Bromelain

  • Fouz, Nour;Amid, Azura;Hashim, Yumi Zuhanis Has-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6709-6714
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    • 2013
  • Background: Breast cancer is a leading cause of death in women. The available chemotherapy drugs have been associated with many side effects. Bromelain has novel medicinal qualities including anti-inflammatory, anti-thrombotic, fibrinolytic and anti-cancer functions. Commercially available bromelain is obtained through tedious methods; therefore, recombinant bromelain may provide a cheaper and simpler choice with similar quality. Materials and Methods: This study aimed to assess the effects of commercial and recombinant bromelain on the cytokinetic behavior of MCF-7 breast cancer cells and their potential as therapeutic alternatives in cancer treatment. Cytotoxic activities of commercial and recombinant bromelain were determined using (sulforhodamine) SRB assay. Next, cell viability assays were conducted to determine effects of commercial and recombinant bromelain on MCF-7 cell cytokinetic behavior. Finally, the established growth kinetic data were used to modify a model that predicts the effects of commercial and recombinant bromelain on MCF-7 cells. Results: Commercial and recombinant bromelain exerted strong effects towards decreasing the cell viability of MCF-7 cells with $IC_{50}$ values of 5.13 ${\mu}g/mL$ and 6.25 ${\mu}g/mL$, respectively, compared to taxol with an $IC_{50}$ value of 0.063 ${\mu}g/mL$. The present results indicate that commercial and recombinant bromelain both have anti-proliferative activity, reduced the number of cell generations from 3.92 to 2.81 for commercial bromelain and to 2.86 for recombinant bromelain, while with taxol reduction was to 3.12. Microscopic observation of bromelain-treated MCF-7 cells demonstrated detachment. Inhibition activity was verified with growth rates decreased dynamically from 0.009 $h^{-1}$ to 0.0059 $h^{-1}$ for commercial bromelain and to 0.0063 $h^{-1}$ for recombinant bromelain. Conclusions: Commercial and recombinant bromelain both affect cytokinetics of MCF-7 cells by decreasing cell viability, demonstrating similar strength to taxol.

Effects of the ethanol extract of Codonopsis Pilosulae Radix on ovalbumin-induced allergic responses in mice (난알부민 유도 알레르기 면역반응에 대한 당삼(黨參)에탄올추출물의 효능 연구)

  • Kang, Seok Yong;Jung, Jin Ki;Lee, Sang Kook;Lee, Seung Ho;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.28 no.2
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    • pp.9-15
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    • 2013
  • Objectives : The root of Codonopsis pilosula (Fr.) Nannf. (Codonopsis Pilosulae Radix) has been traditionally used as a oriental medicine with an anti-thrombotic, antidiabetic, anticancer, and anti-gastric ulcer effects and immunological adjuvant. In this study, we investigated the effect of 70% ethanol extract of Codonopsis Pilosulae Radix (CPR-E) on ovalbumin (OVA)-induced allergic responses in mice. Methods : Mice were sensitized (1, 8, and 15 days) with OVA and airway challenged(22, 24, 26, 28, and 30 days) to induced allergic responses. CPR-E extract at doses of 50 and 100 mg/kg/body weight was orally administered from days 21 to 30 consecutively. The levels of allergic mediators such as histamine, OVA-specific immunoglobulin (Ig) E, and Th1/Th2 cytokines such as IFN-${\gamma}$ and IL-4 were measured in the sera of mice by ELISA. The histological change of lung tissue was observed by hematoxylin and eosin (H&E) staining. Results : CPR-E extract significantly decreased the serum levels of histamine, OVA-specific IgE, and IL-4 compared with those of OVA control group, but significantly increased the serum level of IFN-${\gamma}$. Based on H&E staining, CPR-E extract inhibited the infiltration of inflammatory cells into lung tissues with histological changes. Conclusions : These results indicate that CPR-E extract has anti-inflammatory and anti-allergic responses through regulating the cytokine balance, suggesting that the extract may be useful for the treatment of allergic inflammatory diseases such as bronchial asthma and allergic rhinitis.

LB30057, an Orally Effective Direct Thrombin Inhibitor, Prevents Arterial and Venous Thrombosis in Rats and Dogs

  • Park, Hee-Dong;Kim, Hee-Jin;Oh, Yeong-Soo;Kim, In-Chull;Kim, Yong-Zu;Koh, Hyun-Chul;Shin, In-Chul;Lee, Yong-Hee;Lee, Chang-Ho
    • Archives of Pharmacal Research
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    • v.26 no.3
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    • pp.224-231
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    • 2003
  • The anti-thrombotic effects of LB30057, a direct thrombin inhibitor, were evaluated with in vivo rat and dog thrombosis models. In rats, 1 mg/kg of LB30057 inhibited half of the clot formations in the inferior vena cava at 5 minutes after intravenous application. When measured at 2 hours after oral application, 100 mg/kg prevented approximately half of the clot formations in the inferior vena cava and 50 mg/kg prolonged the mean occlusion time from $15.6{\pm}1.3$ minutes to $47.2{\pm}8.3$ minutes in the carotid artery. In dogs, the formation of thrombus in the jugular vein was reduced to half at a dose range of 20-30 mg/kg at 6 hours after oral application. In addition, the LB30057 dosage required to reduce venous clot formation by approximately 80-90% in dogs was only about 10% of that required for the same reduction in rats. This is probably due to the variation in its time-dependent blood concentration profiles in each species; for example, the plasma half-life of LB71350 in dogs was longer than that in rats ($153.0{\pm}3.0$ vs. $129.7{\pm}12.7$ min at 30 mg/kg, i.v., respectively). AUG, $T_{max},{\;}G_{max}$, and BA in dogs were 59, 8.9, 9.17, and 13.3 times higher than those in rats at oral 30 mg/kg, respectively. Taken together, these results suggest that LB30057 administered orally is effective in the prevention of arterial and venous thrombosis in rats and dogs. It therefore represents a good lead compound for investigations to discover a new, orally available, therapeutic agent for treating thrombotic diseases.

Evaluation of Oxy-radical Scavenging Capacity of Fucoidan (Fucoidan의 Oxy-radical 포획능 평가)

  • Kim, Bong-Hee;Oh, Jung-Min;Kang, Keon-Wook;Kwak, Sang-Hoon;Yun, Sei-Young;Lee, Chul-Ho;Lee, Hyun-Sun;Kim, Sang-Kyum
    • Environmental Analysis Health and Toxicology
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    • v.23 no.1
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    • pp.41-45
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    • 2008
  • Algal fucoidan is a marine polysaccharide containing sulfur with a wide variety of biological activities including anti-inflammatory and anti-thrombotic effects. Although antioxidants can inhibit inflammatory signals through inhibiting activator protein-1 and/or nuclear factor-kappaB activation, it is obscure whether fucoidan directly scavenges oxy-radicals or indirectly regulates oxidant production and/or antioxidant defense system. The antioxidant activities of fucoidan against peroxyl radicals, peroxynitrites and hydroxyl radicals were determined by the total oxy-radical scavenging capacity (TOSC) assay. The specific TOSC values of fucoidan against peroxyl radicals, peroxynitrites or hydroxyl radicals were $282{\pm}60$, $43{\pm}1$ or $40{\pm}1\;TOSC/mg/mL$, respectively. These specific TOSC values against peroxyl radicals, peroxynitrites or hydroxyl radicals are 23, 12, or 13% of the specific TOSC values of glutathione, a positive control, respectively. These results suggest that fucoidan has direct oxy-radical scavenging capacity, which may be related with anti-inflammatory effect of fucoidan.

Screening of Antioxidative, Anti-thrombotic and Anti-atherosclerotic Effects of Moutan Root Bark Extracts (Moutan Root Bark가 항산화활성과 LDL 산화 억제 및 항철소판 응접에 미치는 영향)

  • Ban, Chang-Kye;Lee, Min-Ja;Lee, Hye-Sook;Jung, Hyun-Jung;Kim, Hyuck;Kim, Jai-Eun;Park, Sun-Dong;Park, Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.1
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    • pp.135-143
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    • 2009
  • There is currently increased interest in the identification of antioxidant compounds that are pharmacologically potent and have low or no side effects. Plants produce significant amounts of antioxidants to prevent the oxidative stress caused by photons and oxygen, therefore they represent a potential source of new compounds with antioxidant activity. Moutan Root Sark (MRS) has been frequently used as analgesic. antispasmodic, anti-inflammatory and remedies for female diseases. In this study. the antioxidant activity of extract from MRS was studied in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$ induced human LDL oxidation and the inhibitory effect on collagen induced platelet aggregation. The MRS extracts were found to have a potent scavenging activity, as well as an inhibitory effect on LDL oxidation and on platelet aggregation. In conclusion, the MRS extracts have anti-oxidative and anti-atherosclerotic effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and atherosclerosis.

Screening of Anti-atherosclerotic Effect of Lonicera Flower by Antioxidative and Anti-thrombotic Mechanism (Lonicera Flower의 항산화활성과 LDL 산화 억제효과 및 혈전용해능에 관한 연구)

  • Ju, Shin-Tak;Lee, Min-Ja;Lee, Hye-Sook;Jung, Hyun-Jung;Kim, Hyuck;Kim, Jai-Eun;Park, Sun-Dong;Park, Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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    • pp.1509-1517
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    • 2008
  • The flowers and buds of Lonicera Flower (LF), are used in Korean herbal medicine for latent-heat-clearing, antipyretic, detoxicant and anti-inflammatory ailments. This plant is used worldwide for the treatment of many types of inflammatory disease including respiratory infections, diabetes mellitus, rheumatoid arthritis and play an important role in immune reaction. These pharmaceutical effects of LF looks like to be related to its antioxidant capacity and phytochemicals containing in LF. In this study, the antioxidant activity of extract from LF was studied in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$ induced human LDL oxidation and the inhibitory effect on collagen induced platelet aggregation. The LF extracts were found to have a potent scavenging activity, as well as an inhibitory effect on LDL oxidation and on platelet aggregation. In conclusion, the LF extracts have anti-oxidative and anti-atherosclerotic effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and atherosclerosis.

Alternative Mechanism of Aspirin in Anti-Thrombotic Therapy: Inhibition of Thrombin Activatable Fibrinolysis Inhibitor

  • An, Seong-Soo A.;Greenfield, Robert S.
    • Bulletin of the Korean Chemical Society
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    • v.33 no.9
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    • pp.3048-3054
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    • 2012
  • The use of aspirin is widely recommended for the prevention of heart attacks owing to its ability to inhibit platelet activation by irreversibly blocking cyclooxygenase 1. However, aspirin also affects the fibrinolytic and hemostatic pathways by mechanisms that are not well understood, causing severe hemorrhagic complications. Here, we investigated the ability of aspirin and aspirin metabolites to inhibit thrombin-activatable fibrinolysis inhibitor (TAFI), the major inhibitor of plasma fibrinolysis. TAFI is activated via proteolytic cleavage by the thrombin-thrombomodulin complex to TAFIa, a carboxypeptidase B-like enzyme. TAFIa modulates fibrinolysis by removing the C-terminal arginine and lysine residues from partially degraded fibrin, which in turn inhibits the binding of plasminogen to fibrin clots. Aspirin and its major metabolites, salicylic acid, gentisic acid, and salicyluric acid, inhibit TAFIa carboxypeptidase activity. Salicyluric acid effectively blocks activation of TAFI by thrombin-thrombomodulin; however, salicylates do not inhibit carboxypeptidase N or pancreatic carboxypeptidase B. Aspirin and other salicylates accelerated the dissolution of fibrin clots and reduced thrombus formation in an in vitro model of fibrinolysis. Inhibition of TAFI represents a novel hemostatic mechanism that contributes to aspirin's therapy-associated antithrombotic activity and hemorrhagic complications.

Comparison of the Amino-Acid Content in Pharmacopuncture Extracts Taken from a Scorpion's Body and from Its Tail

  • Lee, Jin-Ho;Shin, Joon-Shik;Chi, Eun-Hya;Lee, In-Hee
    • Journal of Pharmacopuncture
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    • v.16 no.2
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    • pp.33-40
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    • 2013
  • Objective: This study was conducted to investigate the amino-acid compositions of pharmacopuncture extracts taken from the body and from the tail of Buthus martensii Karsch, which are frequently prescribed in Oriental medicine. Methods: Amino acids in hot water and 70% ethanol extracts taken from the scorpion's whole body and from its tail were screened by using high performance liquid chromatography (HPLC). The experiments were performed with linearity, precision and accuracy. Results: The results of the amino-acid-composition analysis showed that the Buthus martensii Karsch extracts contained various amino acids such as aspartic acid, histidine, alanine, tyrosine, and cystine. The amino-acid analysis showed that the hot water extract was more beneficial than the ethanol extract, except for histidine. The amino acids from the tail and the body of the scorpion were compared, and the concentration of aspartic acid in the extract from the scorpion's tail was two times that found in the extract from its body. The results of validation experiments were all satisfactory. Conclusion: Studies on the ingredients in extracts from a scorpion other than buthotoxin may demonstrate that the antiepileptic efficacy, anticancer activity, anti-thrombotic action and analgesic effect are enhanced. Using only the tail of the scorpion when pharmacopuncture is dispensed may be beneficial because the extracts from the tail of the scorpion have higher potency than those from the whole body.

Biological Activities of Low Molecular Weight Substances Fractionated from the Seasoned and Smoked Products of Skipjack Tuna (Euthynus pelamis) (가다랑어 훈연조미제품 유래 저분자물질의 생리활성)

  • LEE Jung Min;CHOI Geun Pyo;WON Moo Ho;KIM Sang Moo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.38 no.4
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    • pp.219-225
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    • 2005
  • We studied the anticancer, antioxidative, ACE inhibitory, antithrombic, and cerebral ischemia inhibitory activities, of low molecular weight substances fractionated from the seasoned and smoked products of skipjack tuna (Euthynus pelamis). Low molecular weight substances fractionated from the liquid extract of seasoned and smoked skipjack tuna powder showed 7 peaks on gel permeation chromatography. Anticancer activity was the highest at Peak 3 $(54.23%)$ followed by Peak 4 $(41.58\%)$. The potency order of antioxidative activity was the highest at Peak 3 $(94.14\%)$ followed by Peak 2 $(82.07\%)$ and Peak 5 $(81.24\%)$. ACE inhibitory activity was the highest at Peak 3 $(67.27\%)$ followed by Peak 5 $(45.62\%)$. But there was weak anti thrombotic effect (PT and APTT) in the low molecular weight substances of the seasoned and smoked products of skipjack tuna. Cerebral ischemia inhibitory activity was the highest at Peak 3 $(80.0\%)$ followed by Peak 5 $(40.0\%)$.