• 한국식품저장유통학회지
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• 제21권5호
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• pp.727-734
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• 2014

식용 및 약용으로 이용되고 있는 우엉 지하부의 혈전 관련 활성과 항산화 활성을 평가하고자, 우엉의 ethanol 추출물 및 이의 순차적 유기용매 분획물을 조제하여 혈액응고 저해 활성, 혈소판 응집저해 활성, 인간 적혈구 용혈활성 및 in-vitro 항산화 활성을 평가하였다. 먼저 우엉 추출 수율은 10.94%로 다른 식용 및 약용식물보다 높았으며, ethanol 추출물의 경우 total polyphenol 함량은 5.01 mg/g으로 낮았으나, 694.53 mg/g의 높은 총당 함량을 나타내었다. 순차적 유기용매 분획의 경우, n-hexane, ethylacetate(EA), n-butanol 분획 수율은 각각 1.62, 0.42 및 5.98%로 나타났으며, 물 잔류물은 85.38%였다. 우엉 시료들의 혈액응고 저해활성을 TT, PT, aPTT를 측정한 결과, ethanol 추출물에서는 유의적인 활성이 나타나지 않았으나, EA 분획에서 강력한 TT, PT, aPTT 연장효과를 확인하였으며, 농도 의존적 혈액응고 저해활성을 확인하였다. 한편 물 잔류물에서는 내인성 혈액응고인자 활성화에 의한 aPTT 감소효과를 확인하여 혈전생성 촉진효과가 있음을 확인하였다. 혈소판 응집저해 활성평가의 경우, 우엉 ethanol 추출물 및 분획물들은 임상에서 사용하는 항혈소판제인 아스피린보다 강력한 저해효과를 나타내었으며, 특히 EA 분획은 정제되지 않은 상태에서도 아스피린의 2배 이상의 강력한 혈소판 응집저해능을 나타내었다. 또한 항산화 활성 평가 결과, EA 분획물은 DPPH 음이온, ABTS 양이온, nitrite에 대해 우수한 소거능 및 환원력을 나타내었다. 또한 우엉 추출물과 분획물들은 0.5 mg/mL 농도까지 인간 적혈구에 대한 특이한 용혈활성을 나타내지 않았다. 상기 결과들은, 우엉 EA 분획물이 천연물 유래의 안전한 항혈전제로 개발 가능함을 제시하고 있다.

• Journal of Chest Surgery
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• 제51권2호
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• pp.114-121
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• 2018

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin $(IL)-1{\beta}$ levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.

• Tuberculosis and Respiratory Diseases
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• 제82권1호
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• pp.53-61
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• 2019

Background: Antiphospholipid antibody syndrome (APS), an important cause of acquired thrombophilia, is diagnosed when vascular thrombosis or pregnancy morbidity occurs with persistently positive antiphospholipid antibodies (aPL). APS is a risk factor for unprovoked recurrence of pulmonary embolism (PE). Performing laboratory testing for aPL after a first unprovoked acute PE is controversial. We investigated if a specific phenotype existed in patients with unprovoked with acute PE, suggesting the need to evaluate them for APS. Methods: We retrospectively reviewed patients with PE and APS (n=24) and those with unprovoked PE with aPL negative (n=44), evaluated 2006-2016 at the Asan Medical Center. We compared patient demographics, clinical manifestations, laboratory findings, and radiological findings between the groups. Results: On multivariate logistic regression analysis, two models of independent risk factors for APS-PE were suggested. Model I included hemoptysis (odds ratio [OR], 12.897; 95% confidence interval [CI], 1.025-162.343), low PE severity index (OR, 0.948; 95% CI, 0.917-0.979), and activated partial thromboplastin time (aPTT; OR, 1.166; 95% CI, 1.040-1.307). Model II included age (OR, 0.930; 95% CI, 0.893-0.969) and aPTT (OR, 1.104; 95% CI, 1.000-1.217). Conclusion: We conclude that patients with first unprovoked PE with hemoptysis and are age <40; have a low pulmonary embolism severity index, especially in risk class I-II; and/or prolonged aPTT (above 75th percentile of the reference interval), should be suspected of having APS, and undergo laboratory testing for aPL.

• 생명과학회지
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• 제14권3호
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• pp.509-513
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• 2004

혈전 관련 질환 예방 및 혈류개선 기능성 식품의 개발을 목표로, 식용 및 약용 산채류 55종의 메탄을 추출물을 조제한 후 트롬빈 저해활성을 검색하였다. 그 결과, 대조군으로 사용된 아스피린보다 우수한 항혈전 활성을 나타내는 붉나무, 사삼, 우산나물, 쥐다래, 참나물, 할미밀망, 큰까치수영, 첫버들 추출물 등 8종을 선별하였으며, aPTT, 혈전 용해활성, 열 안정성, 기타 소화효소 저해활성 등을 평가하며 참나물, 큰까치수영 및 갯버들 추출물을 최종 선별하였다. 참나물의 경우 열안정성이 낮은 반면 소화효소 비저해로 인해 그 이용성이 높으며, 큰 까치수영 및 갯버들의 경우 부분적인 소화효소 저해능이 있으나 우수한 항혈전활성 및 열 안정성을 나타내어 다양한 식품소재로 개발이 가능함을 확인하였다.

• Biomolecules & Therapeutics
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• 제4권2호
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• pp.184-189
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• 1996

General pharmacological studies of LB20304a (a mesylate salt form of a new quinolone antibiotic LB20304 following oral administration of 300 mg/kg and 1000 mg/kg, almost maximum tolerance dose in mice and rat, respectively, were performed in terms of effects on general behaviour, central nervous system, gastrointestinal system, and blood coagulation system in mice and rats. With regards to general behaviour of mice, at oral dose of 300 mg/kg, LB20304a reduced muscle tone and locomotor activity. In terms of CNS, at oral treatment of 300 mg/kg, LB20304a showed some analgesic effects in mice, and oral dose of 1000 mg/kg caused drop in normal body temperature of rat, while it enhanced the pentylenetetrazole-induced clonic convulsion to tonic convulsion and/or death in mice at the doses of unto 300 mg/kg. In addition, LB20304a increased hexobarbital-induced sleeping time two and three times in mice at oral doses of 20 mg/kg and 300 mg/kg, respectively. Rota-rod and traction test in mice were not influenced by the dose of 300 mg/kg and 200 mg/kg, respectively. LB20304a reduced gastric secretion of rat at dose of 1000 mg/kg, and increased intestinal motility of mice at dose of 300 mg/kg. In rats, blood coagulation index, such as PT (prothrombin time) and aPTT (activated partial thromboplastin time) were not affected by the treatment of upto 1000 mg/kg of LB 20304a.

• Journal of Chest Surgery
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• 제13권1호
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• pp.13-20
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• 1980

Heparin would have been used for preventing clotting of blood during extracorporeal circulation and subsequent use of protamine sulfate and made possible the neutralization of heparin. This procedure has been adopted for eliminating one of the great causes of bleeding, especially in cardiac surgery. In this experiment, the hypocoagulability of blood induced by heparin followed by neutralization with treatment of protamine sulfate were estimated by the Lee-White clotting time [CT], partial thromboplastin time [PTT] and protamine titration test. The results were as follows: 1] Comparison of clotting time between the heparinized [2.0 mg/kg] and non-heparinized dogs was done using CT and PT`I` of the blood. In heparinized group [Group I], the CT lasted infinitively and prolongation of PTT [4 times than normal] until 60 minutes. The CT [2 times] and PTT [3 times] has been shortened after 90 minutes, however they returned to normal limit level within 180 minutes. 2] The determination of appropriate ratio of heparin and protamine In vivo were performed. The group II [heparin 2.0 mg/kg, protamine 1.0 mg/kg] revealed rapid decrease of CT and PTT, but returned to normal after 120 minutes. The group III [heparin 2.0 mg/kg, protamine 2.0 mg/kg] returned rapidly to normal within 15 minutes. The group IV [heparin 2.0 mg/kg, protamine 3.0 mg/kg] recovered its normal level after 60 minutes. The group V [heparin 2.0 mg/kg, protamine 4.0 mg/kg] recovered its normal level after 90 minutes. 3] In the combined experimental study In vivo and vitro, the protamine titration test was done using the dog which were given 2.0 mg/kg and 3.0 mg/kg of heparin, respectively and coagulation time were checked after 15, 30, 60 and 120 minutes. The complete neutralization was showed to be heparin-protamine ratio of 1:1 to 1.5. 4] In vitro study, fresh blood was drawn into known amount of heparin content [20, 40, 60 and 100/ug per 1 ml of blood] syringe, thereafter protamine titration test was done. In all cases, the complete neutralization was found in heparin-protamine ratio of 1:0.85 to 1.5. 5] It was found by the present experiment that the ideal heparin-protamine ratio was 1:1 within 60 minutes and 1:0.5 after 60 minutes for avoiding the serious side effect due to overadministration of protamine sulfate.

• 한국식품영양과학회지
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• 제39권12호
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• pp.1790-1799
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• 2010

본 연구에서는 혈전생성을 촉진시키는 주요 원인 중 하나인 흡연하는 30세 이상 60세 이하의 건강한 남성 92명(위약 캡슐군 43명, OPE캡슐군 49명)을 대상으로 양파껍질 추출물(OPE)의 섭취가 항혈전 체계에 긍정적인 영향을 미치는지 그 효과를 검증하고자 시행되었다. 위약-대조군 연구디자인을 통해 OPE를 캡슐 형태로 제조하여 10주간 하루 2회 2캡슐씩 10주간 제공하였다(하루 섭취분량 내 100 mg quercetin 함유). OPE캡슐군과 위약캡슐군 각각의 평균 연령은 $46.1{\pm}7.1$세, $42.4{\pm}8.2$세로 전체 대상자들의 평균 연령은 $44.4{\pm}7.8$세였으며, 연구대상자들의 하루 흡연량은 위약 캡슐군과 OPE캡슐군에서 모두 하루 '20~29개피'의 담배를 피우는 비율이 가장 높은 것으로 나타났다. 체지방과 비만도는 과체중 범위에 속하고 있었으며, 두 군간 임상시험 전후에 유의적인 차이는 없었다. 혈액학 및 생화학적 지표 특성중 HB, RBC, WBC, MCH, RDW, PDW는 임상시험 전후에 유의적인 차이는 없었으나, 혈소판 수는 두 그룹 모두에서 유의적으로 감소(p<0.01), 총 철결합 능(위약캡슐군 p<0.001, OPE캡슐군 p<0.001)과 불포화 철결합 능(위약캡슐군 p<0.001, OPE캡슐군 p<0.01)은 두 그룹 모두 유의적으로 증가하였다. 항혈전 지표에서는 OPE캡슐군에서 10주 후 prothrombin time(PT)(p<0.01)과 activated partial thromboplastin time(aPTT)(p<0.001) 모두 유의적으로 연장되었다. aPTT는 BMI, 체지방 %, 허리둘레와 유의적인 상관성을 보이지 않았지만, PT의 경우 BMI(r=-0.321, p<0.01), 체지방 %(r=-0.375, p<0.001), 허리둘레(r=-0.318, p<0.01)와 유의적인 음의 상관관계를 보였다. 이상과 같이 본 연구에서 OPE캡슐의 섭취는 항혈전 효과가 있음이 확인되었다. 비록 본 연구대상자들이 일부 사무직 위주의 흡연자이고 10주간의 짧은 기간이었다는 단점이 있지만, 별도의 식생활 변화없이 본 시료 섭취만으로 혈액응고시간을 유의적으로 지연시켰다는 점에서 폐기되는 양파껍질의 활용 가능성을 보여 주었다고 사료된다. 앞으로 보다 폭넓은 피험자를 대상으로 한 장기간의 임상시험을 통해 우리나라 국민의 주 사망원인인 과도한 혈전형성으로 인한 혈관계 질환의 감소에 도움을 줄 수 있기를 기대해 본다.

• 한국식품과학회지
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• 제29권2호
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• pp.369-375
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• 1997

식용버섯으로부터 항혈전제제 개발의 소재화연구로 항응고활성의 검색과정에서 높은 활성을 보였던 구름버섯에서 항응고성 다당류를 정제하여 정제다당의 화학적 특성을 검토하였다. 정제는 구름버섯의 알칼리 추출물(CV-0)을 메탄올환류, 에탄올침전 후 3개의 연속적인 DEAE-Toyopearl 650C 이온교환, Sepadex G-100 및 Sepharose CL-6B 겔여과 크로마토그래피와 HPLC에 의하여 실시하였으며 정제다당 CV-40-Va-1의 분자량은 $7.2{\times}105$으로 측정되었다. CV-40-Va-I은 구성당 잔기에 19.32%의 황산기를 함유하는 함황성다당으로서 구성당조성은 fucose:mannose:glucose:galactose가 1.00:0.22:0.20:0.11의 몰 비율로 존재하였다. CV-40-Va-1의 항응고활성은 농도의존성을 보였으며 특히 내인성경로를 통하여 혈액응고를 저해하는 것으로 확인되었다.

• 한국약용작물학회지
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• 제15권2호
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• pp.82-88
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• 2007

From the EtOAc fraction of Eugenia caryophyllata, four compounds were isolated through activity-guided silica gel column chromatography, From the result of spectroscopic data including NMR, MS and IR, the chemical structures of the compounds were determined as 1-allyl-4-hydroxy-3-methoxybezene acetate (eugenol acetate, 1), 1-allyl-4-hydroxy-3-methoxybezene (eugenol, 2), $3{\beta}-hydroxyolean-12-en-28-oic$ acid (oleanolic acid, 3) and $2{\alpha}$, $3{\beta}-dihydroxyolean-12-en-28-oic$ acid (maslinic acid, 4). Compounds 3 and 4 were isolated for the first time from this plant. Also, compounds 1, 2 and 3 exhibited relatively high platelet aggregation inhibitory activity with the $IC_{50}$ values of 0.24, 0.09 and 0.07 mM, respectively. Compound 2 significantly prolonged activated partial thromboplastin time (aPTT) with the value of $124{\pm}11.2$ seconds as compared to the control with the value of $37.5{\pm}2.2$ seconds at the concentration of 50 ${\mu}g/ml$. Compounds 1 and 3 revealed inhibitory activity on farnesyl protein transferase (FPTase) with the $IC_{50}$ values of 0.49 and 0.24 mM and compounds 1 and 2 highly inhibited the growth of rat-H-ras cells with the $Gl_{50}$ values of 6.63 and 5.70 ${\mu}M$, respectively.

• Archives of Pharmacal Research
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• 제23권2호
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• pp.182-186
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• 2000

Chondroitin sulfates proteoglycans were isolated from human placenta. For the identification of enzymatic digestion products of isolated proteoglycan, strong anion exchange-high performance liquid chromatography (SAX-HPLC) was performed. By the action of chondroitin ABC and chondroitin B lyase, three unsaturated disaccharides 2-acetamide-2-deoxy-3-O-($\beta$-D-gluco-4-enepyranosyluronic acid)-D-galactose ($\delta$Di-OS), 2-acetamide-2-deoxy-3-O-($\beta$-D-gluco-4-enepyranosyluronic acid)-6-O-su lfo-D-galactose ($\delta$Di-6S) and 2-acetamide-2-deoxy-3-O-($\beta$-D-gl uco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose ($\delta$Di-4S) were produced from the human placenta proteoglycan. The anticoagulant activity of chondroitin sulfate proteoglycan was evaluated by activated partial thromboplastin time (aPTT) assay and thrombin time (TT) assay. The clotting times of aPTT and TT were increased from 72 to 144 sec and 19 to 27 sec, respectively. The Immune-modulating activity of chondroitin sulfate proteoglycan was examined by cell proliferation assay and these results suggest that it may play a role in suppression of the function of immune-related cells.