• 제목/요약/키워드: Recombinant tissue plasminogen activator

검색결과 28건 처리시간 0.019초

조직형 플라스미노겐 액티베이터와 관련 변이 단백질들을 발현하는 알팔파 형질전환체 (Expression of tissue-type plasminogen activator and its derivative proteins in transgenic alfalfa plants)

  • 심준수;이용;고효림;박효경;김형미;임규희;안기성;김용환;한범수
    • Journal of Plant Biotechnology
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    • 제36권1호
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    • pp.30-37
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    • 2009
  • 의료용 단백질로 중요한 인체 혈관 내피세포 유래 t-PA를 알팔파 식물체를 이용하여 생산하는 기술을 개발하였다. 식물체에서 발현된 t-PA는 동물세포에서 생산된 t-PA와 동등한 시험관 내의 인공 혈전 용해 활성 및 생화학적 특성에서 유사함을 가지고 있었다. 본 연구에서는 식물체에서 발현되는 t-PA 단백질의 알팔파 코돈 이용에 최적화된 합성 유전자이용 양적 증대, 소포체에 표적에 따른 발현양 증대, 6개의 histidine의 부착에 따른 정제의 효율성을 고려하였고 두 종류의 프로모터 (CaMV 35S와 알팔파 Rbcsk-1A)를 이용하여 t-PA 및 파생 단백질들의 발현 효율을 비교 확인하고자 6가지의 식물발현 벡터를 제작하였다. 0.3%의 제초제 살포 후에 저항성을 갖는 알팔파 식물체들의 t-PA 유전자 및 파생 유전자의 genomic DNA내의 삽입 유무는 PCR법을 활용하여 t-PA, 파생 유전자 및 합성 유전자의 크기에 해당하는 1.6 kb의 PCR 산물을 확인 할 수 있었다. 6가지 발현벡터로 형질전환된 알팔파 잎 추출물에서 전체 수용성 단백질내의 t-PA 및 파생 단백질의 평균 발현양은 $9.7-39.5{\mu}g/TSP$ (mg)로 측정되었다. 이중 p221a-t-PAER 발현벡터로 형질전환된 알팔파의 잎 추출물에서 가장 높은 $75.1{\mu}g/TSP$(mg)의 발현양을 나타났다. 알팔파 잎에 발현된 재조합 t-PA 분자량은 상업적으로 판매되는 t-PA와 동일한 68 kDa으로 확인되었다. 형질전환된 알팔파 잎 추출물들의 평균 피브린 용해활성은 3.2-8.1cm를 나타내었다. 또한 t-PA 및 그의 파생 단백질을 발현하는 알팔파 식물체는 야생종 알팔파와 비교했을 때 성장에 있어서 별 다른 차이를 보이지 않았다.

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
    • 한국임상수의학회지
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    • 제34권6호
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    • pp.478-480
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    • 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.

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
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    • 제63권4호
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    • pp.427-432
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    • 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.

The Effect of Locally Administered Fibrinolytic Drugs Following Aneurysmal Subarachnoid Hemorrhage : A Meta-Analysis with Eight Randomized Controlled Studies

  • Jang, Kyoung Min;Choi, Hyun Ho;Nam, Taek Kyun;Park, Yong Sook;Kwon, Jeong Taik;Byun, Jun Soo;Hwang, Doyeon
    • Journal of Korean Neurosurgical Society
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    • 제64권2호
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    • pp.207-216
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    • 2021
  • Objective : Rapid dissolution of blood clots reduces vasospasm and hydrocephalus after subarachnoid hemorrhage (SAH), and locally administered fibrinolytic drugs (LAFDs) could facilitate the dissolution. However, the efficacy of LAFDs remains controversial. The aim of this meta-analysis was to determine the efficacy of LAFDs for vasospasm and hydrocephalus and in clinical outcomes. Methods : From PubMed, EMBASE, and Cochrane database, data were extracted by two authors. Meta-analysis was performed using a random effect model. Inclusion criteria were patients who had LAFDs with urokinase-type or recombinant tissue-plasminogen activator after SAH in comparison with medically untreated patients with fibrinolytic drugs. We only included randomized controlled trials (RCTs) in this analysis. The outcomes of interest were vasospasm, hydrocephalus, mortality, and 90-day unfavorable functional outcome. Results : Data from eight RCTs with 550 patients were included. Pooled-analysis revealed that the LAFDs were significantly associated with lower rates of vasospasm (LAFDs group vs. control group, 26.5% vs. 39.2%; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32-0.73); hydrocephalus (LAFDs group vs. control group, 26.0% vs. 31.6%; OR, 0.54; 95% CI, 0.32-0.91); and mortality (LAFDs group vs. control group, 10.5% vs. 15.7%; OR, 0.58; 95% CI, 0.34-0.99). The proportion of 90-day unfavorable outcomes was lower in the LAFDs group (LAFDs group vs. control group, 32.7% vs. 43.5%; OR, 0.55; 95% CI, 0.37-0.80). Conclusion : This meta-analysis with eight RCTs indicated that LAFDs were significantly associated with lower rates of vasospasm and hydrocephalus after SAH. Thus, LAFDs could consequently reduce mortality and improve clinical outcome after SAH.

PEGylated Erythropoietin Protects against Brain Injury in the MCAO-Induced Stroke Model by Blocking NF-κB Activation

  • Im, Jun Hyung;Yeo, In Jun;Hwang, Chul Ju;Lee, Kyung Sun;Hong, Jin Tae
    • Biomolecules & Therapeutics
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    • 제28권2호
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    • pp.152-162
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    • 2020
  • Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

Endovascular Stroke Therapy Focused on Stent Retriever Thrombectomy and Direct Clot Aspiration : Historical Review and Modern Application

  • Kang, Dong-Hun;Park, Jaechan
    • Journal of Korean Neurosurgical Society
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    • 제60권3호
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    • pp.335-347
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    • 2017
  • Intravenous recombinant tissue plasminogen activator had been the only approved treatment for acute ischemic stroke since its approval in 1995. However, the restrictive time window, numerous contraindications, and its low recanalization rate were all limitations of this modality. Under those circumstances, endovascular stroke therapy went through a great evolution during the past two decades of intravenous thrombolysis. The results of the 2013 randomized trials for endovascular stroke therapy were neutral, although they were limited by insufficient imaging screening at enrollment, early-generation devices with less efficacy, and treatment delays. Huge progress was made in 2015, as there were five randomized clinical trials which all demonstrated the safety and efficacy of endovascular stroke treatment. Despite differences in detail patient enrollment criteria, all 5 trials employed key factors for good functional recovery; (1) screening with non-invasive imaging to identify the proximal occlusion and exclude a large infarct core, (2) using highly effective modern thrombectomy devices mainly with stent retriever, and (3) establishment of a fast workflow to achieve effective reperfusion. The results of those trials indicate that modern thrombectomy devices can allow for faster and more effective reperfusion, which can lead to improved clinical outcomes compared to intravenous thrombolysis alone. These advances in mechanical thrombectomy are promising in the global fight against ischemic stroke-related disability and mortality. Two current mainstreams among such mechanical thrombectomy techniques, "stent retriever thrombectomy" and "direct clot aspiration", are the topic of this review. Stent retriever thrombectomy using Solitaire and Trevo retriever will be firstly discussed. And, the commonalities and the differences between two major clot aspiration thrombectomy techniques; a direct aspiration first pass technique (ADAPT) and forced arterial suction thrombectomy (FAST), will be additionally explained. Finally, details regarding the combination of direct clot aspiration and stent retriever thrombectomy, the switching strategy and the Solumbra technique, will be described.

Efficacy and Safety of Endovascular Treatment in Patients with Internal Carotid Artery Occlusion and Collateral Middle Cerebral Artery Flow

  • Kim, Yong-Won;Kang, Dong-Hun;Kim, Yong-Sun;Hwang, Yang-Ha
    • Journal of Korean Neurosurgical Society
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    • 제62권2호
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    • pp.201-208
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    • 2019
  • Objective : In patients with internal carotid artery (ICA) occlusion, collateral middle cerebral artery (MCA) flow has a protective role against ischemia. However, some of these patients may experience initial major neurological deficits and major worsening on following days. Thus, we investigated the safety and efficacy of endovascular treatment (EVT) for ICA occlusion with collateral MCA flow by comparing clinical outcomes of medical treatment versus EVT. Methods : The inclusion criteria were as follows : 1) acute ischemic stroke with ICA occlusion and presence of collateral MCA flow on transfemoral cerebral angiography (TFCA) and 2) hospital arrival within 12 hours from symptom onset. The treatment strategy was made by the attending physician based on the patient's clinical status and results of TFCA. Results : Eighty-one patients were included (30 medical treatment, 51 EVT). The EVT group revealed a high incidence of intracranial ICA occlusion, longer ipsilesional MCA contrast filling time, and a similar rate of favorable clinical outcome despite a higher mean baseline the National Institutes of Health Stroke Scale (NIHSS) score. By binary logistic regression analysis, intravenous recombinant tissue plasminogen activator and EVT were independent predictors of favorable clinical outcome. In subgroup analysis based on stroke etiology, the non-atherosclerotic group showed a higher baseline NIHSS score, higher incidence of EVT, and a higher rate of distal embolization during EVT in comparison with the atherosclerotic group. Conclusion : In patients with ICA occlusion and collateral MCA flow, decisions regarding treatment strategy based on TFCA can help achieve favorable clinical outcomes. EVT strategy with respect to etiology of ICA occlusion might help achieve better angiographic outcomes.

Computed Tomography for Diagnosing Chylothorax Associated with Cranial Vena Cava Thrombosis in a Dog

  • Jin-Yoo Kim;Gunha Hwang;Sumin Kim;Chi-Oh Yun;Seunghwa Lee;Na-Young Eom;Joong-Hyun Song;Tae Sung Hwang;Hee Chun Lee
    • 한국임상수의학회지
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    • 제41권3호
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    • pp.183-188
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    • 2024
  • A 13-year-old male neutered Miniature Pinscher presented with coughing and dyspnea. The dog had been coughing for the past 4 weeks. The patient had mild dehydration on physical examination, and muffled heart sounds were detected. Thoracic radiographs revealed pleural effusion, which was consistent with chylous effusion based on cytological and biochemical evaluations. Computed tomography (CT) lymphangiography, which was performed via intrametatarsal pad injection, revealed no evidence of thoracic duct rupture or obvious leakage. On CT angiography (CTA), an intraluminal filling defect was identified in the cranial vena cava (CrVC). CrVC thrombosis with secondary chylothorax was diagnosed based on CT lymphangiography and CTA. Clopidogrel, rivaroxaban, and recombinant tissue-plasminogen activator were prescribed. The follow-up CTA, 4 months after diagnosis, revealed a decrease in the thrombus, and no pleural effusion was identified. Although CrVC thrombosis is an uncommon presentation in veterinary patients, thrombus in the CrVC should be considered as a differential diagnosis of chylothorax in dogs. CT lymphangiography and CTA could be helpful in identifying and differentiating the underlying etiologies of chylothorax.