• Title/Summary/Keyword: Plasminogen activator

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Recanalization Rate and Clinical Outcomes of Intravenous Tissue Plasminogen Activator Administration for Large Vessel Occlusion Stroke Patients

  • Min-Hyung Lee;Sang-Hyuk Im;Kwang Wook Jo;Do-Sung Yoo
    • Journal of Korean Neurosurgical Society
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    • v.66 no.2
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    • pp.144-154
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    • 2023
  • Objective : Stroke caused from large vessel occlusion (LVO) has emerged as the most common stroke subtype worldwide. Intravenous tissue plasminogen activator administration (IV-tPA) and additional intraarterial thrombectomy (IA-Tx) is regarded as standard treatment. In this study, the authors try to find the early recanalization rate of IV-tPA in LVO stroke patients. Methods : Total 300 patients undertook IA-Tx with confirmed anterior circulation LVO, were analyzed retrospectively. Brain computed tomography angiography (CTA) was the initial imaging study and acute stroke magnetic resonance angiography (MRA) followed after finished IV-tPA. Early recanalization rate was evaluated by acute stroke MRA within 2 hours after the IV-tPA. In 167 patients undertook IV-tPA only and 133 non-recanalized patients by IV-tPA, additional IA-Tx tried (IV-tPA + IA-Tx group). And 131 patients, non-recanalized by IV-tPA (IV-tPA group) additional IA-Tx recommend and tried according to the patient condition and compliance. Results : Early recanalization rate of LVO after IV-tPA was 12.0% (36/300). In recanalized patients, favorable outcome (modified Rankin Scale, 0-2) was 69.4% (25/36) while it was 32.1% (42/131, p<0.001) in non-recanalized patients. Among 133 patients, non-recanalized after intravenous recombinant tissue plasminogen activator and undertook additional IA-Tx, the clinical outcome was better than not undertaken additional IA-Tx (favorable outcome was 42.9% vs. 32.1%, p=0.046). Analysis according to the perfusion/diffusion (P/D)-mismatching or not, in patient with IV-tPA with IA-Tx (133 patients), favorable outcome was higher in P/D-mismatching patient (52/104; 50.0%) than P/D-matching patients (5/29; 17.2%; p=0.001). Which treatment tired, P/D-mismatching was favored in clinical outcome (iv-tPA only, p=0.008 and IV-tPA with IA-Tx, p=0.001). Conclusion : The P/D-mismatching influences on the recanalization and clinical outcomes of IV-tPA and IA-Tx. The authors would like to propose that we had better prepare IA-Tx when LVO is diagnosed on initial diagnostic imaging. Furthermore, if the patient shows P/D-mismatching on MRA after IV-tPA, additional IA-Tx improves treatment results and lessen the futile recanalization.

A Role of Plasminogen Activators in Animal Reproductive Cells and Organs

  • HwangBo, Yong;Cheong, Hee-Tae;Yang, Boo-Keun;Park, Choon-Keun
    • Reproductive and Developmental Biology
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    • v.38 no.2
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    • pp.63-70
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    • 2014
  • Plasminogen activators (PAs) are serine proteases that convert plasminogen to plasmin. Two type of PAs are urokinase-type PA (uPA) and tissue-type PA (tPA). Plasminogen is present in most extracellular fluids. PAs play in various reproductive processes including implantation, ovulation and fertilization. In the spermatozoa, PAs and PAIs play a role in sperm motility and fertilization. PAs in the sertoli cell are stimulated spermatozoa maturation and sperm activation through the phospholipase A2. The oocyte maturation is the process for fertilization and implantation. PAs in cumulus-oocyte complexes (COCs) are related to oocyte maturation by protein kinase A and C. In the ovulatory process, PAs activity are changed and it are related to reducing the tensile strength of ovarian follicle wall. The uterine environment is important for reproduction and the uterus undergo tissue remodeling. In the uterus and oviduct of mammals, expression and activity of PAs are changed during estrous cycle. Thus, expression and activity of PAs are concerned to many reproductive functions. Therefore, PAs seem to important factor of regulator in reproductive events.

A network pharmacology and molecular docking approach in the exploratory investigation of the biological mechanisms of lagundi (Vitex negundo L.) compounds against COVID-19

  • Robertson G. Rivera;Patrick Junard S. Regidor;Edwin C. Ruamero Jr;Eric John V. Allanigue;Melanie V. Salinas
    • Genomics & Informatics
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    • v.21 no.1
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    • pp.4.1-4.18
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    • 2023
  • Coronavirus disease 2019 (COVID-19) is an inflammatory and infectious disease caused by severe acute respiratory syndrome coronavirus 2 virus with a complex pathophysiology. While COVID-19 vaccines and boosters are available, treatment of the disease is primarily supportive and symptomatic. Several research have suggested the potential of herbal medicines as an adjunctive treatment for the disease. A popular herbal medicine approved in the Philippines for the treatment of acute respiratory disease is Vitex negundo L. In fact, the Department of Science and Technology of the Philippines has funded a clinical trial to establish its potential as an adjunctive treatment for COVID-19. Here, we utilized network pharmacology and molecular docking in determining pivotal targets of Vitex negundo compounds against COVID-19. The results showed that significant targets of Vitex negundo compounds in COVID-19 are CSB, SERPINE1, and PLG which code for cathepsin B, plasminogen activator inhibitor-1, and plasminogen, respectively. Molecular docking revealed that α-terpinyl acetate and geranyl acetate have good binding affinity in cathepsin B; 6,7,4-trimethoxyflavanone, 5,6,7,8,3',4',5'-heptamethoxyflavone, artemetin, demethylnobiletin, gardenin A, geranyl acetate in plasminogen; and 7,8,4-trimethoxyflavanone in plasminogen activator inhibitor-1. While the results are promising, these are bound to the limitations of computational methods and further experimentation are needed to completely establish the molecular mechanisms of Vitex negundo against COVID-19.

Relationship between Plasminogen Activator (PA) and HSP-90 in Uterus Tissue during the Porcine Estrous Cycle (돼지의 발정 주기 동안 자궁조직에서 Plasminogen Activator(PA)와 HSP-90과의 관계)

  • Gu, Ha-Na;Cheong, Hee-Tae;Yang, Boo-Keun;Park, Choon-Keun
    • Reproductive and Developmental Biology
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    • v.36 no.3
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    • pp.219-223
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    • 2012
  • The present study was performed to identify the relationship between plasminogen activator (PA) and Heat Shock Protein-90 (HSP-90) in porcine uterus tissues during the estrous cycle. Porcine uterus tissues were obtained from preovulatory (Pre-Ov), post-ovulatory (Post-Ov) and early to mid-luteal (Early-mid L) stages. The protein was extracted from uterus tissue by using M-PER Mammalian Protein Extraction Reagent. Proteins were refined by RIPA Buffer and quantified by BCA methods. As results, t-PA expression was significantly (p<0.05) higher from pre-ovulatory(Epithelium tissue: $29,067{\mu}g/{\mu}l$, Myometrium tissue: $30,797{\mu}g/{\mu}l$) compared to the post-ovulatory stage(Epithelium tissue: $54,357{\mu}g/{\mu}l$, Myometrium tissue: $53,270{\mu}g/{\mu}l$) and early to mid-luteal stage(Epithelium tissue: $42,380{\mu}g/{\mu}l$, Myometrium tissue: $43,139{\mu}g/{\mu}l$). On the other hand, the uPA expression indicated higher from early to mid-luteal stage (Epithelium tissue: $0.02198{\mu}g/{\mu}l$, Myometrium tissue: $0.02412{\mu}g/{\mu}l$) than pre-ovulatory stage (Epithelium tissue: $0.01577{\mu}g/{\mu}l$, Myometrium tissue: $0.01531{\mu}g/{\mu}l$) and post-ovulatory stage(Epithelium tissue: $0.01414{\mu}g/{\mu}l$, Myometrium tissue: $0.01429{\mu}g/{\mu}l$). However, expression of u-PA did not differ from each estrous cycle in the epithelium tissue and myometrium tissue(p<0.05). Expression of HSP-90 was differ t-PA and u-PA from pre-ovulatory in Epithelium tissue($25,423{\mu}g/{\mu}l$) and early to mid-luteal stage in epithelium tissue($177,922{\mu}g/{\mu}l$) and myometrium tissue($26,664{\mu}g/{\mu}l$). These results suggest that HSP-90 and u-PA were related with change of uterus cycle according to the reformation of the tissues in porcine uterus.

Effects of Cumulus Cells and Follicular Fluid on Plasminogen Activator Activity during In Vitro Maturation of Porcine Oocytes

  • Ann Ji-Young;Sa Soo-Jin;Cao Yang;Lee Sang-Young;Cheon Hee-Tae;Yang Boo-Keun;Park Choon-Keun
    • Reproductive and Developmental Biology
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    • v.30 no.2
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    • pp.135-141
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    • 2006
  • The present study was conducted to investigate the effects of cumulus cells and porcine follicular fluid (pFF) on plasminogen activator (PA) activity and oocytes maturation in vitro in the pig. The cumulus-oocyte complexes (COCs) and denuded oocytes (DOs) were incubated in NCSU-23 medium with or without 10% pFF for 0, 24, or 48 hr. In the presence of cumulus cells, the proportions of oocytes matured to metaphase-II stage were significantly (P<0.05) higher in medium with pFF than without pFF (69.8 vs. 37.7%, respectively). When COCs and DOs were cultured in the presence of pFF, tissue-type PA (tPA), urokinase-type PA (uPA), and tPA-PA inhibitor (tPA-PAI) were observed in COCs, and PA activities were higher at 48 hr than 24 hr. When COCs and DOs were cultured in the absence of pFF, tPA and tPA-PAI were observed in COCs, and PA activities were increased as duration of culture increased. No PA activities were detected in DOs regardless of pFF supplementation. When porcine oocytes were cultured in the presence of pFF for 24 and 48 hrs, the activities of tPA-PAI, tPA, and uPA were observed in both COCs and DOs. In medium of absence of pFF, PA activities were observed in oocytes with cumulus cells only. On the other hand, three plasminogen-dependent lytic bands (tPA-PAI, tPA, and uPA) were observed in pFF cultures. Particularly uPA activity was higher than the other kinds of PA activity. When oocytes and cumulus cells were separated from porcine COCs at 0 hr of culture, tPA-PAI, tPA, and uPA were detected in cumulus cells at 48 hr of culture, but no PA activities were in DOs. The presence of pFF and cumulus cells in maturation medium stimulated not only nuclear and cytoplasmic maturation in porcine COCs, but also PA production by cumulus cells and COCs. It is possible that PAs produced by cumulus cells migrated through the gap junction between oocyte and cumulus cells. These results suggest that porcine oocytes have no ability to produce PA themselves.

Sp1 Decoy Oligodeoxynucleotides Inhibit Serum-induced Mesangial Cell Proliferation (Sp1 Decoy Oligodeoxynucleotides에 의한 사구체 혈관간세포 증식억제 효과)

  • Chae Young Mi;Kim Sung Young;Park Kwan Kyu;Chang Young Chae
    • KSBB Journal
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    • v.19 no.5
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    • pp.335-340
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    • 2004
  • Mesangial expansion caused by cell proliferation and glomerular extracellular matrix accumulation is one of the earliest renal abnormalties observed at the onset of hyperglycemia in diabetes mellitus. Transcription factor Sp1 is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation, and is assumed to play an essential role in mesangial expansion, transforming growth factor (TGF)-$\beta$1, plasminogen activator inhibitor (PAI)-1. We have generated a phosphorothioated double-stranded Sp1-decoy oligodeoxynucleotide that effectively blocks Sp1 binding to the promoter region for transcriptional regulation of TGF-$\beta$1 and PAI-1. The Sp1 decoy oligodeoxynucleotide suppressed transcription of these cytokines and proliferation of primary rat mesangial cells in response to serum stimulation. These results suggest that the Sp1 decoy oligodeoxynucleotide could bea powerful tool in preventing the pathogenesis of renal hypertrophy.

A Successfully Treated Case of Recurrent Focal Segmental Glomerulosclerosis (FSGS) with Plasmapheresis and High dose Methylprednisolone Pulse Therapy

  • Her, Sun Mi;Lee, Keum Hwa;Shin, Jae Il
    • Childhood Kidney Diseases
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    • v.21 no.2
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    • pp.165-168
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    • 2017
  • Focal segmental glomerulosclerosis (FSGS) in children, which is a kind of nephrotic syndrome showing steroid resistance, usually progresses to a substantial number of end stage renal disease (ESRD). Although the pathogenesis of primary FSGS is unclear, several recent studies have reported that FSGS is associated with circulating immune factors such as soluble urokinase-type plasminogen activator receptor (suPAR) or anti-CD40 autoantibody. We report a successfully treated case of a 19-year-old female patient who experienced a recurrence of primary FSGS. After the diagnosis of FSGS, the patient progressed to ESRD and received a kidney transplantation (KT). Three days later, recurrence was suspected through proteinuria and hypoalbuminemia. She has been performed plasmapheresis and high dose methylprednisolone pulse therapy and shown remission status without increasing proteinuria for four years after KT. In conclusion, strong immunosuppressive therapy may be helpful for a good prognosis of recurrent FSGS, suppressing several immunologic circulating factors related disease pathogenesis.

Studies of Attachment of Fibroblasts on Microcarriers for the Production of Tissue Plasminogen Activator (TPA 생산을 위한 섬유 세포의 미립 담체와의 접착성에 관한 연구)

  • 강재구;박형환;이현용
    • KSBB Journal
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    • v.4 no.2
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    • pp.104-109
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    • 1989
  • Among commercially available five different types of micro-carriers, collagen coated Cytodex III supports the best cell growth and production of Tissue type Plasminogen Activator from fibroblasts for all three various kinds of media(FBS, horse serum containing and serum free medium). 95% of attachment yield is obtained with Cytodex III in FBS containing medium compared to about 70% in serum free medium. However, higher production of TPA can be observed in horse serum containing and serum free media as $1.2\;\mu\textrm{g}/\;ml$ and $0.7 \mu\textrm{g}/\;ml$, respectively with $5.5{\times}10^6$ cells/ ml and $0.7{\times}10^6$ cells/ ml under perfusiom chemostat operations.

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