• Title/Summary/Keyword: Plasminogen

Search Result 246, Processing Time 0.03 seconds

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
    • /
    • v.33 no.9
    • /
    • pp.3048-3054
    • /
    • 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.

Tissue- and Reproductive Organ-specific Expression of Protease Nexin-1 in Sprague-Dawley Rat (흰쥐에서 단백질 분해효소 저해제, Nexin-1의 조직 및 생식기관 특이적 유전자 발현)

  • 고정재;김남근;김진규;최명진;정형민;서승염;김윤희;이현환;차광열
    • Development and Reproduction
    • /
    • v.2 no.2
    • /
    • pp.135-140
    • /
    • 1998
  • Protease Nexin-1 (PN-1) inhibits the activity of several serine proteases including thrombin, urokinase (uPA)-type plasminogen activator and trypsin. Tissue- and reproductive organ-specific mRNA levels of the PN-1 were investigated in Sprague-Dawley adult rat. PN-1 mRNA expression in rats was found in brain (forebrain, hindbrain), heart, liver, lung, ovary and oviduct. The level of PN-1 mRNA in male and female among the tissues was the highest in forebrain of the female. PN-1 expression in reproductive organs was found only in ovary and oviduct. These results suggest that PN-1 expression is dependent on the sex and may be related to folliculogenesis and early embryogenesis.

  • PDF

Development of Exposure Biomarkers for Endocrine Disrupting Chemicals Using DNA Microarray (DNA 마이크로어레이를 이용한 내분비장애물질 노출지표 개발)

  • Yang, Mi-Hi
    • Environmental Analysis Health and Toxicology
    • /
    • v.20 no.4 s.51
    • /
    • pp.327-332
    • /
    • 2005
  • 장기간 노출 시 발암 등 인체 유해성을 갖는 환경유래 내분비장애물질(endocrine disrupting chemicals, EDCs)에 대한 선택적이고 민감한 노출지표를 개발하기 위하여 본 연구에서는 DNA microarray를 이용하였다. 피험자는 아직 특별한 질환을 갖지 않는 18세 이상 연령, 성을 맞춘 EDCs고농도 노출군(N = 16)과 저농도군(N = 16)으로 구성되었다. 노출정도 구분은 10년 이상 거주지가 K산업폐기물 소각장과 2.5 km 반경 내, 외 인지에 따라 고노출군,저노출군으로 구분하였다. 피험자의 말초혈에서 total RNA를 분리, 각 군당 B인씩 pool로 cDNA를 합성하여 oligonucleotide DNA 칩에 적용하였다. 유전자발현의 차이를 GenePixPro 4.0 software를 이용하여 분석하였다. 총 3장의 칩을 이용하여 공통적으로 저노출군보다 고노출군에서 2배 이상 발현의 증가를 보인 유전자는 plasminogen activator(PLAT)등 12종이 관찰되었고, l/2이하로 발현의 감소를 보인 유전자는 kallikrein 3 (KLK3)등 29종이었다. 이 들 유전자는 PLAT등 면역계 반응에 관여하는 유전자 및 apoptosis, transport, G protein, chromatin, 암화, 발생 (development), 대사 등에 관여하는 유전자들이었다. 그러므로 KLK3등 본 연구에서 발굴한 유전자는 향후 확대된 인구에서 본 연구 결과의 확인을 통하여 EDCs특이적 노출지표로써, 나아가 암 등 EDCs관련 질병의 기전 및 병인학을 구명하는데 이용가치가 높다고 사료된다.

Clinical Consideration of Obese Infertile Women (비만 불임여성에 대한 임상적 고찰)

  • Nam, Yoon-Sung;Jeong, Chang-Jin;Kim, Nam-Keun;Yoon, Tae-Ki;Cha, Kwang-Yul
    • Clinical and Experimental Reproductive Medicine
    • /
    • v.29 no.3
    • /
    • pp.209-214
    • /
    • 2002
  • Objective : To analyze the clinical characteristics of obese infertile women. Material and Method: Height, weight, body mass index, menstrual pattern, glucose, insulin, glucose/insulin ratio, dehydroepiandrosterone sulfate (DHEA-S), testosterone, free testosterone and plasminogen activator inhibitor (PAI-1) of 15 obese infertile women were tested. Results: Of 15 obese infertile women, the number of diabetes mellitus, hyperinsulinemia, and insulin resistance was 2 (13%), 2 (13%), 2 (13%), respectively. The incidence of increased DHEA-S, testosterone, and free testosterone was 7 (47%), 1 (7%), 6 (40%), respectively. Notably, all patients showed increased PAI-1. Conclusions: Obesity is associated with infertility as well as many kinds of health problems. Obesity is closely related to insulin resistance and it also causes hyperandrogenism. Increased PAI-1 is one of the important causes of thrombophilia. Consequently, in the workup of obese infertile patient, many aspects of health problems should be considered.

Giant Right Atrial Thrombi Formation Associated with Hemodialysis Catheter Placement in a Dog

  • Shin, Du-Ree;Yang, Hyuck-Joo;Kim, Hye-Young;Song, Kun-Ho;Seo, Kyoung-Won
    • Journal of Veterinary Clinics
    • /
    • v.34 no.6
    • /
    • pp.478-480
    • /
    • 2017
  • A Cocker spaniel (7-year-old, female) was presented with one week of anorexia, halitosis, oral ulcer, intermittent vomiting, acute weight loss and 3-day history of oliguria. The patient was diagnosed with acute on chronic kidney disease and pancreatitis. Hemodialysis was continued three times a week (total 7 sessions) with improved clinical signs and kidney panel, but presented with another episode of abdominal distention, respiratory distress, and large bowel diarrhea. Echocardiography revealed nearly totally occlusive thrombus in the cranial vena cava, as well as a right atrial mass of approximately $2cm{\times}1cm$. The patient was treated with catheter removal, thrombolysis and anticoagulation therapy with recombinant tissue plasminogen activator. During anticoagulation therapy, size of atrial thrombus was not changed and heart function was not improved after treatment. Since clinical signs were deteriorated, the patient was euthanized by owner's request. Catheter-related giant thrombus in right atrium is a rare complication and treatment guideline for atrial thrombus does not exist. This case is first report of hemodialysis catheter-induced thrombus in Korea.

Stroke and Sleep (뇌졸중과 수면)

  • Jeong, Seung-Cheol
    • Sleep Medicine and Psychophysiology
    • /
    • v.9 no.1
    • /
    • pp.5-8
    • /
    • 2002
  • Stroke is a leading cause of death in most developed countries and some developing countries including South Korea. It is well known that stroke has is related in some way with several sleep disorders. At first, the onset time of stroke varies according to circadian rhythm. Early morning is the most prevalent time and late evening the least. The changes of blood pressure, catecholamine level, plasminogen activity and aggregation of platelet during sleep have been suggested as possible mechanisms. Sleep apnea (SA), a representative disorder in the field of sleep medicine, is found in more than 70% of acute stroke patients compared to 2-5% of the general population. Various sleep related breathing disorders occur after stroke and snoring is a distinct risk factor for stroke. So the relationship between stroke and SA is obvious, but the cause and effect are still not clearly known. Also, stroke may cause many sleep related problems such as insomnia, hypersomnia, parasomnia and changes in sleep architecture. Patients, family members and even medical personnel often ignore stroke-related sleep problems, being concerned only about the stroke itself. The clinical impacts of sleep problems in stroke patients may be significant not only in terms of quality of life but also as a risk factor or prognostic factor for stroke. More attention should be paid to the sleep problems of stroke patients.

  • PDF

Peroxiredoxin 6 Promotes Lung Cancer Cell Invasion by Inducing Urokinase-Type Plasminogen Activator via p38 Kinase, Phosphoinositide 3-Kinase, and Akt

  • Lee, Seung Bum;Ho, Jin-Nyoung;Yoon, Sung Hwan;Kang, Ga Young;Hwang, Sang-Gu;Um, Hong-Duck
    • Molecules and Cells
    • /
    • v.28 no.6
    • /
    • pp.583-588
    • /
    • 2009
  • The peroxiredoxin family of peroxidase has six mammalian members (Prx 1-6). Considering their frequent up-regulation in cancer cells, Prxs may contribute to cancer cells' survival in face of oxidative stress. Here, we show that Prx 6 promotes the invasiveness of lung cancer cells, accompanied by an increase in the activity of phosphoinositide 3-kinase (PI3K), the phosphorylation of p38 kinase and Akt, and the protein levels of uPA. Functional studies reveal that these components support Prx 6-induced invasion in the sequence p38 kinase/PI3K, Akt, and uPA. The findings provide a new understanding of the action of Prx 6 in cancer.

A Case of Factor XII Deficiency Which was Found in Recurrent Spontaneous Abortion (반복자연유산 환자에서 발견된 응고인자 12 부족증 1례)

  • Nam, Y.S;Kim, I.H.;Yoon, T.K.;Lee, C.N.;Cha, K.Y.
    • Clinical and Experimental Reproductive Medicine
    • /
    • v.26 no.2
    • /
    • pp.271-274
    • /
    • 1999
  • Activated factor XII (FXIIc: Hageman factor) is a central component of the contact activation system of blood coagulation, fibrinolysis, and kinin formation. Although patients deficient in FXIIc (up to 50% of normal) do not show increased bleeding tendency, thrombotic complications were reported in 8% to 10% among these patients. The reduced generation of bradykinin resulting in diminished release of tissue plasminogen activator is proposed as a cause of thrombosis in factor XII (FXII)-deficient patients. Similarly, in patients with elevated levels of circulating antiphospholipid antibodies, hemostasis may be impaired resulting in excessive thrombophilia. Both vascular and placental thromboses because of antiphospholipid antibodies or FXIIc deficiency have been reported to be associated with recurrent fetal loss. We have experienced a case of factor XII deficiency in woman with recurrent spontaneous abortion. So we report this case with a brief review of literatures.

  • PDF

Paradigm Shift in Intra-Arterial Mechanical Thrombectomy for Acute Ischemic Stroke : A Review of Randomized Controlled Trials after 2015

  • Sheen, Jae Jon;Kim, Young Woo
    • Journal of Korean Neurosurgical Society
    • /
    • v.63 no.4
    • /
    • pp.427-432
    • /
    • 2020
  • Three randomized control trials (RCTs), published in 2013, investigated efficacy of mechanical thrombectomy in large vessel occlusions and did not show better results compared to intravenous (IV) recombinant tissue-type plasminogen activator (tPA) alone. However, most clinicians treating stroke consider mechanical thrombectomy as the standard treatment rather than using IV tPA alone. This paradigm shift was based on five RCTs investigating efficacy of mechanical thrombectomy in acute ischemic stroke conducted from 2010 to 2015. They demonstrated that mechanical thrombectomy was effective and safe in acute ischemic stroke with anterior circulation occlusion when performed within 6 hours of stroke onset. There are four reasons underlying the different results observed between the trials conducted in 2013 and 2015. First, the three RCTs of 2013 used low-efficiency thrombectomy devices. Second, the three RCTs used insufficient image selection criteria. Third, following the initial presentation at the hospital, reperfusion treatment required a long time. Fourth, the three RCTs showed a low rate of successful recanalization. Time is the most important factor in the treatment of acute ischemic stroke. However, current trends utilize advanced imaging techniques, such as diffusion-weighted imaging and multi-channel computer tomographic perfusion, to facilitate the detection of core infarction, penumbra, and collateral flows. These efforts demonstrate that patient selection may overcome the barriers of time in specific cases.

Acute Ischemic Stroke Involving Both Anterior and Posterior Circulation Treated by Endovascular Revascularization for Acute Basilar Artery Occlusion via Persistent Primitive Trigeminal Artery

  • Imahori, Taichiro;Fujita, Atsushi;Hosoda, Kohkichi;Kohmura, Eiji
    • Journal of Korean Neurosurgical Society
    • /
    • v.59 no.4
    • /
    • pp.400-404
    • /
    • 2016
  • We report a case of acute ischemic stroke involving both the anterior and posterior circulation associated with a persistent primitive trigeminal artery (PPTA), treated by endovascular revascularization for acute basilar artery (BA) occlusion via the PPTA. An otherwise healthy 67-year-old man experienced sudden loss of consciousness and quadriplegia. Magnetic resonance imaging showed an extensive acute infarction in the right cerebral hemisphere, and magnetic resonance angiography showed occlusion of the right middle cerebral artery (MCA) and BA. Because the volume of infarction in the territory of the right MCA was extensive, we judged the use of intravenous tissue plasminogen activator to be contraindicated. Cerebral angiography revealed hypoplasia of both vertebral arteries and the presence of a PPTA from the right internal carotid artery. A microcatheter was introduced into the BA via the PPTA and revascularization was successfully performed using a Merci Retriever with adjuvant low-dose intraarterial urokinase. After treatment, his consciousness level and right motor weakness improved. Although persistent carotid-vertebrobasilar anastomoses such as a PPTA are relatively rare vascular anomalies, if the persistent primitive artery is present, it can be an access route for mechanical thrombectomy for acute ischemic stroke.